Hydrogen inhalation reduced epithelial apoptosis in ventilator-induced lung injury via a mechanism involving nuclear factor-kappa B activation

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Huang, Chien-Sheng [Department of Cardiothoracic Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA (United States); Division of Thoracic Surgery, Department of Surgery, Taipei-Veterans General Hospital and National Yang-Ming University School of Medicine, Taipei, Taiwan (China); Kawamura, Tomohiro; Peng, Ximei [Department of Cardiothoracic Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA (United States); Tochigi, Naobumi [Department of Pathology, University of Pittsburgh Medical Center, PA (United States); Shigemura, Norihisa [Department of Cardiothoracic Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA (United States); Billiar, Timothy R. [Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA (United States); Nakao, Atsunori, E-mail: anakao@imap.pitt.edu [Department of Cardiothoracic Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA (United States); Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA (United States); Toyoda, Yoshiya [Department of Cardiothoracic Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA (United States)

2011-05-06

Highlights: {yields} Hydrogen is a regulatory molecule with antiinflammatory and antiapoptotic protective effects. {yields} There is very limited information on the pathways regulated in vivo by the hydrogen. {yields} Antiapoptotic abilities of hydrogen were explained by upregulation of the antiapoptotic gene. {yields} NF{kappa}B activation during hydrogen treatment was correlated with elevated antiapoptotic protein. {yields} NF{kappa}B activation associated with increase Bcl-2 may contribute to cytoprotection of hydrogen. -- Abstract: We recently demonstrated the inhalation of hydrogen gas, a novel medical therapeutic gas, ameliorates ventilator-induced lung injury (VILI); however, the molecular mechanisms by which hydrogen ameliorates VILI remain unclear. Therefore, we investigated whether inhaled hydrogen gas modulates the nuclear factor-kappa B (NF{kappa}B) signaling pathway. VILI was generated in male C57BL6 mice by performing a tracheostomy and placing the mice on a mechanical ventilator (tidal volume of 30 ml/kg or 10 ml/kg without positive end-expiratory pressure). The ventilator delivered either 2% nitrogen or 2% hydrogen in balanced air. NF{kappa}B activation, as indicated by NF{kappa}B DNA binding, was detected by electrophoretic mobility shift assays and enzyme-linked immunosorbent assay. Hydrogen gas inhalation increased NF{kappa}B DNA binding after 1 h of ventilation and decreased NF{kappa}B DNA binding after 2 h of ventilation, as compared with controls. The early activation of NF{kappa}B during hydrogen treatment was correlated with elevated levels of the antiapoptotic protein Bcl-2 and decreased levels of Bax. Hydrogen inhalation increased oxygen tension, decreased lung edema, and decreased the expression of proinflammatory mediators. Chemical inhibition of early NF{kappa}B activation using SN50 reversed these protective effects. NF{kappa}B activation and an associated increase in the expression of Bcl-2 may contribute, in part, to the

Insights into iron and nuclear factor-kappa B (NF-kappaB) involvement in chronic inflammatory processes in peritoneal endometriosis.

Science.gov (United States)

Defrère, Sylvie; González-Ramos, Reinaldo; Lousse, Jean-Christophe; Colette, Sébastien; Donnez, Olivier; Donnez, Jacques; Van Langendonckt, Anne

2011-08-01

Endometriosis is a chronic pelvic inflammatory process. Local inflammation is known to play a role in pain and infertility associated with the disease, and may be extensively involved in molecular and cellular processes leading to endometriosis development. In this review, we focus on two inflammatory mediators clearly implicated in the pathogenesis of endometriosis, iron and NF-kappaB, and their potential association. Iron is essential for all living organisms, but excess iron results in toxicity and is linked to pathological disorders. In endometriosis patients, iron overload has been demonstrated in the different compartments of the peritoneal cavity (peritoneal fluid, endometriotic lesions, peritoneum and macrophages). This iron overload affects numerous mechanisms involved in endometriosis development. Moreover, iron can generate free radical species able to react with a wide range of cellular constituents, inducing cellular damage. Overproduction of reactive oxygen species also impairs cellular function by altering gene expression via regulation of redox-sensitive transcription factors such as NF-kappaB, which is clearly implicated in endometriosis. Indeed, NF-kappaB is activated in endometriotic lesions and peritoneal macrophages of endometriosis patients, which stimulates synthesis of proinflammatory cytokines, generating a positive feedback loop in the NF-kappaB pathway. NF-kappaB-mediated gene transcription promotes a variety of processes, including endometriotic lesion establishment, maintenance and development. In conclusion, iron and NF-kappaB appear to be linked and both are clearly involved in endometriosis development, making these pathways an attractive target for future treatment and prevention of this disease.

Diarctigenin, a lignan constituent from Arctium lappa, down-regulated zymosan-induced transcription of inflammatory genes through suppression of DNA binding ability of nuclear factor-kappaB in macrophages.

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Kim, Byung Hak; Hong, Seong Su; Kwon, Soon Woo; Lee, Hwa Young; Sung, Hyeran; Lee, In-Jeong; Hwang, Bang Yeon; Song, Sukgil; Lee, Chong-Kil; Chung, Daehyun; Ahn, Byeongwoo; Nam, Sang-Yoon; Han, Sang-Bae; Kim, Youngsoo

2008-11-01

Diarctigenin was previously isolated as an inhibitor of nitric oxide (NO) production in macrophages from the seeds of Arctium lappa used as an alternative medicine for the treatment of inflammatory disorders. However, little is known about the molecular basis of these effects. Here, we demonstrated that diarctigenin inhibited the production of NO, prostaglandin E(2), tumor necrosis factor-alpha, and interleukin (IL)-1beta and IL-6 with IC(50) values of 6 to 12 miciroM in zymosan- or lipopolysaccharide-(LPS) activated macrophages. Diarctigenin attenuated zymosan-induced mRNA synthesis of inducible NO synthase (iNOS) and also inhibited promoter activities of iNOS and cytokine genes in the cells. Because nuclear factor (NF)-kappaB plays a pivotal role in inflammatory gene transcription, we next investigated the effect of diarctigenin on NF-kappaB activation. Diarctigenin inhibited the transcriptional activity and DNA binding ability of NF-kappaB in zymosan-activated macrophages but did not affect the degradation and phosphorylation of inhibitory kappaB (IkappaB) proteins. Moreover, diarctigenin suppressed expression vector NF-kappaB p65-elicited NF-kappaB activation and also iNOS promoter activity, indicating that the compound could directly target an NF-kappa-activating signal cascade downstream of IkappaB degradation and inhibit NF-kappaB-regulated iNOS expression. Diarctigenin also inhibited the in vitro DNA binding ability of NF-kappaB but did not affect the nuclear import of NF-kappaB p65 in the cells. Taken together, diarctigenin down-regulated zymosan- or LPS-induced inflammatory gene transcription in macrophages, which was due to direct inhibition of the DNA binding ability of NF-kappaB. Finally, this study provides a pharmacological potential of diarctigenin in the NF-kappaB-associated inflammatory disorders.

Buddleja officinalis suppresses high glucose-induced vascular smooth muscle cell proliferation: role of mitogen-activated protein kinases, nuclear factor-kappaB and matrix metalloproteinases.

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Lee, Yun Jung; Kim, Jin Sook; Kang, Dae Gill; Lee, Ho Sub

2010-02-01

Diabetes mellitus is a well-established risk factor for vascular diseases caused by atherosclerosis. In the development of diabetic atherogenesis, vascular smooth muscle cell proliferation is recognized as a key event. Thus, we aimed to investigate whether an ethanol extract of Buddleja officinalis (EBO) suppresses high glucose-induced proliferation in primary cultured human aortic smooth muscle cells (HASMC). [(3)H]-thymidine incorporation revealed that incubation of HASMC with a high concentration of glucose (25 mmol/L) increased cell proliferation. The expression levels of cell cycle protein were also increased by treatment with high glucose concentration. Pretreatment of HASMC with EBO significantly attenuated the increase of high glucose-induced cell proliferation as well as p38 mitogen-activated protein kinases (MAPK) and JNK phosphorylation. EBO suppressed high glucose-induced matrix metalloproteinase (MMP)-9 activity in a dose-dependent manner. In addition, EBO suppressed nuclear factor-kappaB (NF-kappaB) nuclear translocation and transcriptional activity in high glucose conditions. Taken together, the present data suggest that EBO could suppress high glucose-induced atherosclerotic processes through inhibition of p38, JNK, NF-kappaB and MMP signal pathways in HASMC.

Mitochondria mediate tumor necrosis factor-alpha/NF-kappaB signaling in skeletal muscle myotubes

Science.gov (United States)

Li, Y. P.; Atkins, C. M.; Sweatt, J. D.; Reid, M. B.; Hamilton, S. L. (Principal Investigator)

1999-01-01

Tumor necrosis factor-alpha (TNF-alpha) is implicated in muscle atrophy and weakness associated with a variety of chronic diseases. Recently, we reported that TNF-alpha directly induces muscle protein degradation in differentiated skeletal muscle myotubes, where it rapidly activates nuclear factor kappaB (NF-kappaB). We also have found that protein loss induced by TNF-alpha is NF-kappaB dependent. In the present study, we analyzed the signaling pathway by which TNF-alpha activates NF-kappaB in myotubes differentiated from C2C12 and rat primary myoblasts. We found that activation of NF-kappaB by TNF-alpha was blocked by rotenone or amytal, inhibitors of complex I of the mitochondrial respiratory chain. On the other hand, antimycin A, an inhibitor of complex III, enhanced TNF-alpha activation of NK-kappaB. These results suggest a key role of mitochondria-derived reactive oxygen species (ROS) in mediating NF-kappaB activation in muscle. In addition, we found that TNF-alpha stimulated protein kinase C (PKC) activity. However, other signal transduction mediators including ceramide, Ca2+, phospholipase A2 (PLA2), and nitric oxide (NO) do not appear to be involved in the activation of NF-kappaB.

Resveratrol enhances ultraviolet B-induced cell death through nuclear factor-{kappa}B pathway in human epidermoid carcinoma A431 cells

Energy Technology Data Exchange (ETDEWEB)

Roy, Preeti; Kalra, Neetu; Nigam, Nidhi; George, Jasmine [Proteomics Laboratory, Indian Institute of Toxicology Research (CSIR), P.O. Box 80, M.G. Marg, Lucknow 226 001 (India); Ray, Ratan Singh; Hans, Rajendra K. [Photobiology Laboratory, Indian Institute of Toxicology Research (CSIR), P.O. Box 80, M.G. Marg, Lucknow 226 001 (India); Prasad, Sahdeo [Proteomics Laboratory, Indian Institute of Toxicology Research (CSIR), P.O. Box 80, M.G. Marg, Lucknow 226 001 (India); Shukla, Yogeshwer, E-mail: yogeshwer_shukla@hotmail.com [Proteomics Laboratory, Indian Institute of Toxicology Research (CSIR), P.O. Box 80, M.G. Marg, Lucknow 226 001 (India)

2009-06-26

Resveratrol has been reported to suppress cancer progression in several in vivo and in vitro models, whereas ultraviolet B (UVB), a major risk for skin cancer, is known to induce cell death in cancerous cells. Here, we investigated whether resveratrol can sensitize A431 human epidermoid carcinoma cells to UVB-induced cell death. We examined the combined effect of UVB (30 mJ/cm{sup 2}) and resveratrol (60 {mu}M) on A431 cells. Exposure of A431 carcinoma cells to UVB radiation or resveratrol can inhibit cell proliferation and induce apoptosis. However, the combination of resveratrol and UVB exposure was associated with increased proliferation inhibition of A431 cells compared with either agent alone. Furthermore, results showed that resveratrol and UVB treatment of A431 cells disrupted the nuclear factor-kappaB (NF-{kappa}B) pathway by blocking phosphorylation of serine 536 and inactivating NF-{kappa}B and subsequent degradation of I{kappa}B{alpha}, which regulates the expression of survivin. Resveratrol and UVB treatment also decreased the phosphorylation of tyrosine 701 of the important transcription factor signal transducer activator of transcription (STAT1), which in turn inhibited translocation of phospho-STAT1 to the nucleus. Moreover, resveratrol/UVB also inhibited the metastatic protein LIMK1, which reduced the motility of A431 cells. In conclusion, our study demonstrates that the combination of resveratrol and UVB act synergistically against skin cancer cells. Thus, resveratrol is a potential chemotherapeutic agent against skin carcinogenesis.

Biological variation and reference intervals for circulating osteopontin, osteoprotegerin, total soluble receptor activator of nuclear factor kappa B ligand and high-sensitivity C-reactive protein

DEFF Research Database (Denmark)

Sennels, H P; Jacobsen, Søren; Jensen, T

2007-01-01

Objective. Monitoring inflammatory diseases and osteoclastogenesis with osteopontin (OPN), osteoprotegerin (OPG), total soluble receptor activator of nuclear factor kappa B ligand (total sRANKL) and high-sensitivity C-reactive protein (hsCRP) has recently attracted increased interest. The purpose...

Inhibition of IkappaB kinase-nuclear factor-kappaB signaling pathway by 3,5-bis(2-flurobenzylidene)piperidin-4-one (EF24), a novel monoketone analog of curcumin.

Science.gov (United States)

Kasinski, Andrea L; Du, Yuhong; Thomas, Shala L; Zhao, Jing; Sun, Shi-Yong; Khuri, Fadlo R; Wang, Cun-Yu; Shoji, Mamoru; Sun, Aiming; Snyder, James P; Liotta, Dennis; Fu, Haian

2008-09-01

The nuclear factor-kappaB (NF-kappaB) signaling pathway has been targeted for therapeutic applications in a variety of human diseases, includuing cancer. Many naturally occurring substances, including curcumin, have been investigated for their actions on the NF-kappaB pathway because of their significant therapeutic potential and safety profile. A synthetic monoketone compound termed 3,5-bis(2-flurobenzylidene)piperidin-4-one (EF24) was developed from curcumin and exhibited potent anticancer activity. Here, we report a mechanism by which EF24 potently suppresses the NF-kappaB signaling pathway through direct action on IkappaB kinase (IKK). We demonstrate that 1) EF24 induces death of lung, breast, ovarian, and cervical cancer cells, with a potency about 10 times higher than that of curcumin; 2) EF24 rapidly blocks the nuclear translocation of NF-kappaB, with an IC(50) value of 1.3 microM compared with curcumin, with an IC(50) value of 13 microM; 3) EF24 effectively inhibits tumor necrosis factor (TNF)-alpha-induced IkappaB phosphorylation and degradation, suggesting a role of this compound in targeting IKK; and 4) EF24 indeed directly inhibits the catalytic activity of IKK in an in vitro-reconstituted system. Our study identifies IKK as an effective target for EF24 and provides a molecular explanation for a superior activity of EF24 over curcumin. The effective inhibition of TNF-alpha-induced NF-kappaB signaling by EF24 extends the therapeutic application of EF24 to other NF-kappaB-dependent diseases, including inflammatory diseases such as rheumatoid arthritis.

Renin-angiotensin system inhibition ameliorates CCl4-induced liver fibrosis in mice through the inactivation of nuclear transcription factor kappa B.

Science.gov (United States)

Saber, Sameh; Mahmoud, Amr A A; Helal, Noha S; El-Ahwany, Eman; Abdelghany, Rasha H

2018-06-01

Therapeutic interventions for liver fibrosis are still limited due to the complicated molecular pathogenesis. Renin-angiotensin system (RAS) seems to contribute to the development of hepatic fibrosis. Therefore, we aimed to examine the effect of RAS inhibition on CCl 4 -induced liver fibrosis. Mice were treated with silymarin (30 mg·kg -1 ), perindopril (1 mg·kg -1 ), fosinopril (2 mg·kg -1 ), or losartan (10 mg·kg -1 ). The administration of RAS inhibitors improved liver histology and decreased protein expression of alpha smooth muscle actin (α-SMA) and hepatic content of hydroxyproline. These effects found to be mediated via inactivation of nuclear transcription factor kappa B (NFκB) pathway by the inhibition of NFκB p65 phosphorylation at the Ser536 residue and phosphorylation-induced degradation of nuclear factor kappa-B inhibitor alpha (NFκBia) subsequently inhibited NFκB-induced TNF-α and TGF-β1, leading to lower levels of tissue inhibitor of metalloproteinase-1 (TIMP-1) and vascular endothelial growth factor (VEGF). We concluded that the tissue affinity of the angiotensin converting enzyme inhibitors (ACEIs) has no impact on its antifibrotic activity and that interfering the RAS either through the inhibition of ACE or the blockade of AT1R has the same therapeutic benefit. These results suggest RAS inhibitors as promising candidates for further clinical trials in the management of hepatic fibrosis.

Suppressor of cytokine signalling (SOCS)-3 protects beta cells against IL-1beta-mediated toxicity through inhibition of multiple nuclear factor-kappaB-regulated proapoptotic pathways

DEFF Research Database (Denmark)

Karlsen, Allan Ertman; Heding, P E; Frobøse, H

2004-01-01

The proinflammatory cytokine IL-1beta induces apoptosis in pancreatic beta cells via pathways dependent on nuclear factor-kappaB (NF-kappaB), mitogen-activated protein kinase, and protein kinase C. We recently showed suppressor of cytokine signalling (SOCS)-3 to be a natural negative feedback reg...... regulator of IL-1beta- and IFN-gamma-mediated signalling in rat islets and beta cell lines, preventing their deleterious effects. However, the mechanisms underlying SOCS-3 inhibition of IL-1beta signalling and prevention against apoptosis remain unknown....

Effects of cardiopulmonary bypass on lung nuclear factor-kappa B activity, cytokine release, and pulmonary function in dogs

Directory of Open Access Journals (Sweden)

Gaisheng Yang

2015-12-01

Full Text Available Objective(s: To study the effect of cardiopulmonary bypass (CPB on nuclear factor-kappa B (NF-кB and cytokine expression and pulmonary function in dogs. Materials and Methods: Twelve male mongrel dogs were divided into a methylprednisolone group (group M and a control group (group C. All animals underwent aortic and right atrial catheterization under general anesthesia. Changes in pulmonary function and hemodynamics were monitored and the injured site was histologically evaluated. Results: The activity of NF-кB and myeloperoxidase (MPO, levels of tumor necrosis factor (TNF-α, interleukin (IL-1β, IL-6, and IL-8, and the wet/dry (W/D weight ratio were significantly higher after CPB than before CPB in both groups (P

c-Jun NH2-terminal kinase activity in subcutaneous adipose tissue but not nuclear factor-kappaB activity in peripheral blood mononuclear cells is an independent determinant of insulin resistance in healthy individuals

DEFF Research Database (Denmark)

Sourris, Karly C; Lyons, Jasmine G; de Courten, Maximilian

2009-01-01

Chronic low-grade activation of the immune system (CLAIS) predicts type 2 diabetes via a decrease in insulin sensitivity. Our study investigated potential relationships between nuclear factor-kappaB (NF-kappaB) and c-Jun NH(2)-terminal kinase (JNK) pathways-two pathways proposed as the link between...

Apple, Cherry, and Blackcurrant Increases Nuclear Factor Kappa B Activation in Liver of Transgenic Mice

DEFF Research Database (Denmark)

Balstad, Trude; Paur, Ingvild; Poulsen, Morten

2010-01-01

Nuclear factor kappa B (NF-B) is essential in normal physiology, and several human disorders involve inappropriate regulation of NF-B. Diets dominated by plant-based foods protect against chronic diseases, and several food derived compounds have been identified as promising NF-B modulators. We...... investigated the effects of diets supplemented with apple, blackcurrant, or cherries on lipopolysaccharide (LPS)-induced NF-B activation in transgenic NF-B-luciferase mice. Whole body and organ specific NF-B activities were determined. The mice had ad libitum access to the respective experimental diets for 7...... slightly higher whole-body NF-B activation at 4 h, and all 3 experimental groups had higher NF-B activation at 6 h. LPS-induced NF-B activation in liver was increased with all 3 experimental diets, but no effects were observed in other organs. Our findings indicate that high intakes of lyophilized fruits...

Uncaria rhynchophylla and Rhynchophylline inhibit c-Jun N-terminal kinase phosphorylation and nuclear factor-kappaB activity in kainic acid-treated rats.

Science.gov (United States)

Hsieh, Ching-Liang; Ho, Tin-Yun; Su, Shan-Yu; Lo, Wan-Yu; Liu, Chung-Hsiang; Tang, Nou-Ying

2009-01-01

Our previous studies have shown that Uncaria rhynchophylla (UR) can reduce epileptic seizures. We hypothesized that UR and its major component rhynchophylline (RH), reduce epileptic seizures in rats treated with kainic acid (KA) by inhibiting nuclear factor-kappaB (NF-kappaB) and activator-protein-1 (AP-1) activity, and by eliminating superoxide anions. Therefore, the level of superoxide anions and the DNA binding activities of NF-kappaB and AP-1 were measured. Sprague-Dawley (SD) rats were pre-treated with UR (1.0 g/kg, i.p.), RH (0.25 mg/kg, i.p.), or valproic acid (VA, 250 mg/kg, i.p.) for 3 days and then KA was administered intra-peritoneal (i.p.). The results indicated that UR, RH, and VA can reduce epileptic seizures and the level of superoxide anions in the blood. Furthermore, KA was demonstrated to induce the DNA binding activities of NF-kappaB and AP-1. However, these inductions were inhibited by pre-treatment with UR, RH, or VA for 3 days. Moreover, UR and RH were shown to be involved in the suppression of c-Jun N-terminal kinase (JNK) phosphorylation. This study suggested that UR and RH have antiepileptic effects in KA-induced seizures and are associated with the regulation of the innate immune system via a reduction in the level of superoxide anions, JNK phosphorylation, and NF-kappaB activation.

[Nuclear factor-kappaB mRNA and protein expression in stomach tissue of rats with gastric ulcer recurrence and effect of jianwei yuyang granule on its expression].

Science.gov (United States)

Ling, Jiang-Hong; Li, Jia-Bang; Shen, Ding-Zhu; Zhou, Bing

2006-03-01

To observe the inflammatory reaction, nuclear factor-kappaB (NF-kappaB) mRNA and protein expression in stomach tissue of rats with gastric ulcer recurrence and the effect of Jianwei Yuyang granule (JYG) on them. Gastric ulcer and its recurrent lesion were successively induced by acetic acid and interliukin1-beta (IL-1beta), and the model rats were divided into the sham operation group, the model group, the omeprazole (correction of omepraxole) group and the JYG group to observe the state of chronic inflammatory cell, neutrophil count, NF-kappaBmRNA and protein expression in stomach tissue. On the 16th and 92th day after administration, the increase of chronic inflammatory cell, neutrophil, NF-kappaBmRNA and protein expression in the model group was more significant than those in the sham operated group (P ulcer induced by acetic acid. JYG may suppress inflammatory reaction by inhibiting the activation and expression of NF-kappaB in stomach tissue, which may be one of the mechanisms of JYG in preventing the recurrence of gastric ulcer.

Induction of activator protein (AP)-1 and nuclear factor-kappaB by CD28 stimulation involves both phosphatidylinositol 3-kinase and acidic sphingomyelinase signals.

Science.gov (United States)

Edmead, C E; Patel, Y I; Wilson, A; Boulougouris, G; Hall, N D; Ward, S G; Sansom, D M

1996-10-15

A major obstacle in understanding the signaling events that follow CD28 receptor ligation arises from the fact that CD28 acts as a costimulus to TCR engagement, making it difficult to assess the relative contribution of CD28 signals as distinct from those of the TCR. To overcome this problem, we have exploited the observation that activated human T cell blasts can be stimulated via the CD28 surface molecule in the absence of antigenic challenge; thus, we have been able to observe the response of normal T cells to CD28 activation in isolation. Using this system, we observed that CD28 stimulation by B7-transfected CHO cells induced a proliferative response in T cells that was not accompanied by measurable IL-2 production. However, subsequent analysis of transcription factor generation revealed that B7 stimulation induced both activator protein-1 (AP-1) and nuclear factor-kappaB (NF-kappaB) complexes, but not NF-AT. In contrast, engagement of the TCR by class II MHC/superantigen, either with or without CD28 ligation, resulted in the induction of NF-AT, AP-1, and NF-kappaB as well as IL-2 production. Using selective inhibitors, we investigated the signaling pathways involved in the CD28-mediated induction of AP-1 and NF-kappaB. This revealed that NF-kappaB generation was sensitive to chloroquine, an inhibitor of acidic sphingomyelinase, but not to the phosphatidylinositol 3-kinase inhibitor, wortmannin. In contrast, AP-1 generation was inhibited by wortmannin and was also variably sensitive to chloroquine. These data suggest that in activated normal T cells, CD28-derived signals can stimulate proliferation at least in part via NF-kappaB and AP-1 generation, and that this response uses both acidic sphingomyelinase and phosphatidylinositol 3-kinase-linked pathways.

Activation of nuclear transcription factor-kappaB in mouse brain induced by a simulated microgravity environment

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Wise, Kimberly C.; Manna, Sunil K.; Yamauchi, Keiko; Ramesh, Vani; Wilson, Bobby L.; Thomas, Renard L.; Sarkar, Shubhashish; Kulkarni, Anil D.; Pellis, Neil R.; Ramesh, Govindarajan T.

2005-01-01

Microgravity induces inflammatory responses and modulates immune functions that may increase oxidative stress. Exposure to a microgravity environment induces adverse neurological effects; however, there is little research exploring the etiology of these effects resulting from exposure to such an environment. It is also known that spaceflight is associated with increase in oxidative stress; however, this phenomenon has not been reproduced in land-based simulated microgravity models. In this study, an attempt has been made to show the induction of reactive oxygen species (ROS) in mice brain, using ground-based microgravity simulator. Increased ROS was observed in brain stem and frontal cortex with concomitant decrease in glutathione, on exposing mice to simulated microgravity for 7 d. Oxidative stress-induced activation of nuclear factor-kappaB was observed in all the regions of the brain. Moreover, mitogen-activated protein kinase kinase was phosphorylated equally in all regions of the brain exposed to simulated microgravity. These results suggest that exposure of brain to simulated microgravity can induce expression of certain transcription factors, and these have been earlier argued to be oxidative stress dependent.

Glycogen synthase kinase-3 inhibition disrupts nuclear factor-kappaB activity in pancreatic cancer, but fails to sensitize to gemcitabine chemotherapy

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Mamaghani Shadi

2009-04-01

Full Text Available Abstract Background Aberrant activation NF-kappaB has been proposed as a mechanism of drug resistance in pancreatic cancer. Recently, inhibition of glycogen synthase kinase-3 has been shown to exert anti-tumor effects on pancreatic cancer cells by suppressing NF-kappaB. Consequently, we investigated whether inhibition of GSK-3 sensitizes pancreatic cancer cells to the chemotherapeutic agent gemcitabine. Methods GSK-3 inhibition was achieved using the pharmacological agent AR-A014418 or siRNA against GSK-3 alpha and beta isoforms. Cytotoxicity was measured using a Sulphorhodamine B assay and clonogenic survival following exposure of six different pancreatic cancer cell lines to a range of doses of either gemcitabine, AR-A014418 or both for 24, 48 and 72 h. We measured protein expression levels by immunoblotting. Basal and TNF-alpha induced activity of NF-kappaB was assessed using a luciferase reporter assay in the presence or absence of GSK-3 inhibition. Results GSK-3 inhibition reduced both basal and TNF-alpha induced NF-kappaB luciferase activity. Knockdown of GSK-3 beta reduced nuclear factor kappa B luciferase activity to a greater extent than GSK-3 alpha, and the greatest effect was seen with dual knockdown of both GSK-3 isoforms. GSK-3 inhibition also resulted in reduction of the NF-kappaB target proteins XIAP, Bcl-XL, and cyclin D1, associated with growth inhibition and decreased clonogenic survival. In all cell lines, treatment with either AR-A014418, or gemcitabine led to growth inhibition in a dose- and time-dependent manner. However, with the exception of PANC-1 where drug synergy occurred with some dose schedules, the inhibitory effect of combined drug treatment was additive, sub-additive, or even antagonistic. Conclusion GSK-3 inhibition has anticancer effects against pancreatic cancer cells with a range of genetic backgrounds associated with disruption of NF-kappaB, but does not significantly sensitize these cells to the standard

Glycogen synthase kinase-3 inhibition disrupts nuclear factor-kappaB activity in pancreatic cancer, but fails to sensitize to gemcitabine chemotherapy

International Nuclear Information System (INIS)

Mamaghani, Shadi; Patel, Satish; Hedley, David W

2009-01-01

Aberrant activation NF-kappaB has been proposed as a mechanism of drug resistance in pancreatic cancer. Recently, inhibition of glycogen synthase kinase-3 has been shown to exert anti-tumor effects on pancreatic cancer cells by suppressing NF-kappaB. Consequently, we investigated whether inhibition of GSK-3 sensitizes pancreatic cancer cells to the chemotherapeutic agent gemcitabine. GSK-3 inhibition was achieved using the pharmacological agent AR-A014418 or siRNA against GSK-3 alpha and beta isoforms. Cytotoxicity was measured using a Sulphorhodamine B assay and clonogenic survival following exposure of six different pancreatic cancer cell lines to a range of doses of either gemcitabine, AR-A014418 or both for 24, 48 and 72 h. We measured protein expression levels by immunoblotting. Basal and TNF-alpha induced activity of NF-kappaB was assessed using a luciferase reporter assay in the presence or absence of GSK-3 inhibition. GSK-3 inhibition reduced both basal and TNF-alpha induced NF-kappaB luciferase activity. Knockdown of GSK-3 beta reduced nuclear factor kappa B luciferase activity to a greater extent than GSK-3 alpha, and the greatest effect was seen with dual knockdown of both GSK-3 isoforms. GSK-3 inhibition also resulted in reduction of the NF-kappaB target proteins XIAP, Bcl-X L , and cyclin D1, associated with growth inhibition and decreased clonogenic survival. In all cell lines, treatment with either AR-A014418, or gemcitabine led to growth inhibition in a dose- and time-dependent manner. However, with the exception of PANC-1 where drug synergy occurred with some dose schedules, the inhibitory effect of combined drug treatment was additive, sub-additive, or even antagonistic. GSK-3 inhibition has anticancer effects against pancreatic cancer cells with a range of genetic backgrounds associated with disruption of NF-kappaB, but does not significantly sensitize these cells to the standard chemotherapy agent gemcitabine. This lack of synergy might be

Real-time monitoring of inflammation status in 3T3-L1 adipocytes possessing a secretory Gaussia luciferase gene under the control of nuclear factor-kappa B response element

Energy Technology Data Exchange (ETDEWEB)

Nagasaki, Haruka; Yoshimura, Takeshi [Department of Life Sciences, Graduate School of Bioresources, Mie University, Tsu 514-8507 (Japan); Aoki, Naohito, E-mail: n-aoki@bio.mie-u.ac.jp [Department of Life Sciences, Graduate School of Bioresources, Mie University, Tsu 514-8507 (Japan)

2012-04-13

Highlights: Black-Right-Pointing-Pointer Inflammation status in adipocytes can be monitored by the new assay system. Black-Right-Pointing-Pointer Only an aliquot of conditioned medium is required without cell lysis. Black-Right-Pointing-Pointer Inflammation-attenuating compounds can be screened more conveniently. -- Abstract: We have established 3T3-L1 cells possessing a secretory Gaussia luciferase (GLuc) gene under the control of nuclear factor-kappa B (NF-{kappa}B) response element. The 3T3-L1 cells named 3T3-L1-NF-{kappa}B-RE-GLuc could differentiate into adipocyte as comparably as parental 3T3-L1 cells. Inflammatory cytokines such as tumor necrosis factor (TNF)-{alpha} and interleukin (IL)-1{beta} induced GLuc secretion of 3T3-L1-NF-{kappa}B-RE-GLuc adipocytes in a concentration- and time-dependent manner. GLuc secretion of 3T3-L1-NF-{kappa}B-RE-GLuc adipocytes was also induced when cultured with RAW264.7 macrophages and was dramatically enhanced by lipopolysaccharide (LPS)-activated macrophages. An NF-{kappa}B activation inhibitor BAY-11-7085 and an antioxidant N-acetyl cysteine significantly suppressed GLuc secretion induced by macrophages. Finally, we found that rosemary-derived carnosic acid strongly suppressed GLuc secretion induced by macrophages and on the contrary up-regulated adiponectin secretion. Collectively, by using 3T3-L1-NF-{kappa}B-RE-GLuc adipocytes, inflammation status can be monitored in real time and inflammation-attenuating compounds can be screened more conveniently.

Mangiferin, a novel nuclear factor kappa B-inducing kinase inhibitor, suppresses metastasis and tumor growth in a mouse metastatic melanoma model

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Takeda, Tomoya; Tsubaki, Masanobu; Sakamoto, Kotaro; Ichimura, Eri; Enomoto, Aya; Suzuki, Yuri [Division of Pharmacotherapy, Kinki University School of Pharmacy, Kowakae, Higashi-, Osaka (Japan); Itoh, Tatsuki [Department of Food Science and Nutrition, Kinki University School of Agriculture, Nara, Nara (Japan); Imano, Motohiro [Department of Surgery, Kinki University School of Medicine, Osakasayama, Osaka (Japan); Tanabe, Genzoh; Muraoka, Osamu [Laboratory of Pharmaceutical Organic Chemistry, School of Pharmacy, Kinki University, Kowakae, Higashi-, Osaka (Japan); Matsuda, Hideaki [Department of Natural Drugs Resources, Kinki University School of Pharmacy, Kowakae, Higashi-, Osaka (Japan); Satou, Takao [Department of Pathology, Kinki University School of Medicine, Osakasayama, Osaka (Japan); Nishida, Shozo, E-mail: nishida@phar.kindai.ac.jp [Division of Pharmacotherapy, Kinki University School of Pharmacy, Kowakae, Higashi-, Osaka (Japan)

2016-09-01

Advanced metastatic melanoma, one of the most aggressive malignancies, is currently without reliable therapy. Therefore, new therapies are urgently needed. Mangiferin is a naturally occurring glucosylxanthone and exerts many beneficial biological activities. However, the effect of mangiferin on metastasis and tumor growth of metastatic melanoma remains unclear. In this study, we evaluated the effect of mangiferin on metastasis and tumor growth in a mouse metastatic melanoma model. We found that mangiferin inhibited spontaneous metastasis and tumor growth. Furthermore, mangiferin suppressed the nuclear translocation of nuclear factor kappa B (NF-κB) and expression of phosphorylated NF-κB-inducing kinase (NIK), inhibitor of kappa B kinase (IKK), and inhibitor of kappa B (IκB) and increases the expression of IκB protein in vivo. In addition, we found that mangiferin inhibited the expression of matrix metalloproteinases (MMPs) and very late antigens (VLAs) in vivo. Mangiferin treatment also increased the expression of cleaved caspase-3, cleaved Poly ADP ribose polymerase-1 (PARP-1), p53 upregulated modulator of apoptosis (PUMA), p53, and phosphorylated p53 proteins, and decreased the expression of Survivin and Bcl-associated X (Bcl-xL) proteins in vivo. These results indicate that mangiferin selectivity suppresses the NF-κB pathway via inhibition of NIK activation, thereby inhibiting metastasis and tumor growth. Importantly, the number of reported NIK selective inhibitors is limited. Taken together, our data suggest that mangiferin may be a potential therapeutic agent with a new mechanism of targeting NIK for the treatment of metastatic melanoma. - Highlights: • Mangiferin prolongs survival in mice by inhibiting metastasis and tumor growth • Mangiferin selectivity suppresses the NF-κB pathway via inhibition of NIK activation • Mangiferin regulates the expression of MMPs, VLAs, and apoptosis regulatory proteins.

Functional inhibition of NF-kappa B signal transduction in alpha v alpha beta 3 integrin expressing endothelial cells by using RGD-PEG-modified adenovirus with a mutant I kappa B gene

NARCIS (Netherlands)

Ogawara, K; Kuldo, JM; Oosterhuis, K; Kroesen, BJ; Rots, MG; Trautwein, C; Kimura, T; Haisma, HJ; Molema, G

2006-01-01

In order to selectively block nuclear factor kappa B (NF-kappa B)-dependent signal transduction in angiogenic endothelial cells, we constructed an alpha v beta 3 integrin specific adenovirus encoding dominant negative I kappa B (dnI kappa B) as a therapeutic gene. By virtue of RGD modification of

IκBζ, an atypical member of the inhibitor of nuclear factor kappa B family, is induced by γ-irradiation in glioma cells, regulating cytokine secretion and associated with poor prognosis.

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Brennenstuhl, Heiko; Armento, Angela; Braczysnki, Anne Kristin; Mittelbronn, Michel; Naumann, Ulrike

2015-11-01

The inhibitor of nuclear factor kappa B zeta (IκBζ) is an atypical member of the IκB protein family. Its function in regulating the activity of the transcription factor nuclear factor kappa B (NFκB) as well as its involvement in cancer-associated processes is poorly understood. In glioma patients, enhanced expression of IκBζ in tumor specimen is associated with poor prognosis. Here we report that IκBζ is upregulated in a glioma cell line resistant towards NFκB-dependent non-apoptotic cell death. Upon γ-irradiation of glioma cells, IκBζ expression is enhanced, and subsequently serves as a transcriptional activator of the tumor promoting cytokines interleukin (IL-6), IL-8 and chemokine (C-X-C motif) ligand 1 (CXCL1) that are known to be involved in glioma associated inflammatory processes. In contrast, shRNA-mediated knockdown of IκBζ reduces the expression of the aforementioned cytokines. We propose a previously unappreciated role of IκBζ in the inflammatory micromilieu as well as progression in glioma.

Inhibition of nuclear factor-kappa B activation decreases survival of Mycobacterium tuberculosis in human macrophages.

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Xiyuan Bai

Full Text Available Nuclear factor-kappa B (NFκB is a ubiquitous transcription factor that mediates pro-inflammatory responses required for host control of many microbial pathogens; on the other hand, NFκB has been implicated in the pathogenesis of other inflammatory and infectious diseases. Mice with genetic disruption of the p50 subunit of NFκB are more likely to succumb to Mycobacterium tuberculosis (MTB. However, the role of NFκB in host defense in humans is not fully understood. We sought to examine the role of NFκB activation in the immune response of human macrophages to MTB. Targeted pharmacologic inhibition of NFκB activation using BAY 11-7082 (BAY, an inhibitor of IκBα kinase or an adenovirus construct with a dominant-negative IκBα significantly decreased the number of viable intracellular mycobacteria recovered from THP-1 macrophages four and eight days after infection. The results with BAY were confirmed in primary human monocyte-derived macrophages and alveolar macrophages. NFκB inhibition was associated with increased macrophage apoptosis and autophagy, which are well-established killing mechanisms of intracellular MTB. Inhibition of the executioner protease caspase-3 or of the autophagic pathway significantly abrogated the effects of BAY. We conclude that NFκB inhibition decreases viability of intracellular MTB in human macrophages via induction of apoptosis and autophagy.

Dose-rate effects of protons on in vivo activation of nuclear factor-kappa B and cytokines in mouse bone marrow cells

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Rithidech, K.N.; Rusek, A.; Reungpatthanaphong, P.; Honikel, L.; Simon, S.R.

2010-05-28

The objective of this study was to determine the kinetics of nuclear factor-kappa B (NF-{kappa}B) activation and cytokine expression in bone marrow (BM) cells of exposed mice as a function of the dose rate of protons. The cytokines included in this study are pro-inflammatory [i.e., tumor necrosis factor-alpha (TNF-{alpha}), interleukin-1beta (IL-1{beta}), and IL-6] and anti-inflammatory cytokines (i.e., IL-4 and IL-10). We gave male BALB/cJ mice a whole-body exposure to 0 (sham-controls) or 1.0 Gy of 100 MeV protons, delivered at 5 or 10 mGy min{sup -1}, the dose and dose rates found during solar particle events in space. As a reference radiation, groups of mice were exposed to 0 (sham-controls) or 1 Gy of {sup 137}Cs {gamma} rays (10 mGy min{sup -1}). After irradiation, BM cells were collected at 1.5, 3, 24 h, and 1 month for analyses (five mice per treatment group per harvest time). The results indicated that the in vivo time course of effects induced by a single dose of 1 Gy of 100 MeV protons or {sup 137}Cs {gamma} rays, delivered at 10 mGy min{sup -1}, was similar. Although statistically significant levels of NF-{kappa}B activation and pro-inflammatory cytokines in BM cells of exposed mice when compared to those in the corresponding sham controls (Student's t-test, p < 0.05 or < 0.01) were induced by either dose rate, these levels varied over time for each protein. Further, only a dose rate of 5 mGy min{sup -1} induced significant levels of anti-inflammatory cytokines. The results indicate dose-rate effects of protons.

Inhibitory effects of curcumin and capsaicin on phorbol ester-induced activation of eukaryotic transcription factors, NF-kappaB and AP-1.

Science.gov (United States)

Surh, Y J; Han, S S; Keum, Y S; Seo, H J; Lee, S S

2000-01-01

Recently, considerable attention has been focused on identifying dietary and medicinal phytochemicals that can inhibit, retard or reverse the multi-stage carcinogenesis. Spices and herbs contain phenolic substances with potent antioxidative and chemopreventive properties. Curcumin, a yellow colouring agent from turmeric and capsaicin, a pungent principle of red pepper exhibit profound anticarcinogenic and antimutagenic activities. Two well-defined eukaryotic transcription factors, nuclear factor-kappa B (NF-kappaB) and activator protein 1 (AP-1) have been implicated in pathogenesis of many human diseases including cancer. These transcription factors are known to be activated by a wide array of external stimuli, such as tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA), tumor necrosis factor, reactive oxygen species, bacterial lipopolysaccharide, and ultraviolet. In the present study, we found that topical application of TPA onto dorsal skin of female ICR mice resulted in marked activation of epidermal NF-kappaB and AP-1. Curcumin and capsaicin, when topically applied prior to TPA, significantly attenuated TPA-induced activation of each transcription factor in mouse skin. Likewise, both compounds inhibited NF-kappaB and AP-1 activation in cultured human promyelocytic leukemia (HL-60) cells stimulated with TPA. Based on these findings, it is likely that curcumin and capsaicin exert anti-tumor promotional effects through suppression of the tumor promoter-induced activation of transcription factors, NF-kappaB and AP-1.

Receptor activator of nuclear factor kappa B (RANK as a determinant of peri-implantitis

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Rakić Mia

2013-01-01

Full Text Available Background/Aim. Peri-implantitis presents inflammatory process that affects soft and hard supporting tissues of osseointegrated implant based on inflammatory osteoclastogenesis. The aim of this study was to investigate whether receptor activator of nuclear factor kappa B (RANK concentrations in peri-implant crevicular fluid could be associated with clinical parameters that reflect inflammatory nature of peri-implantitis. Methods. The study included 67 patients, 22 with diagnosed peri-implantitis, 22 persons with healthy peri-implant tissues and 23 patients with periodontitis. Clinical parameters from each patient were recorded and samples of peri-implant/gingival crevicular fluid were collected for the enzyme-linked immunosorbent assay (ELISA analysis. Results. RANK concentration was significantly increased in samples from the patients with periimplantitis when compared to healthy implants (p < 0.0001, where the average levels were 9 times higher. At the same time RANK concentration was significantly higher in periimplantitis than in periodontitis sites (p < 0.0001. In implant patients pocket depths and bleeding on probing values were positively associated with high RANK concentrations (p < 0.0001. Conclusion. These results revealed association of increased RANK concentration in samples of periimplant/ gingival crevicular fluid with peri-implant inflammation and suggests that RANK could be a pathologic determinant of peri-implantitis, thereby a potential parameter in assessment of peri-implant tissue inflammation and a potential target in designing treatment strategies.

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

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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.

Cdc25A promotes cell survival by stimulating NF-{kappa}B activity through I{kappa}B-{alpha} phosphorylation and destabilization

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Hong, Hey-Young; Choi, Jiyeon [Department of Biochemistry, College of Natural Sciences, Kangwon National University, 192-1 Hyoja-2-dong, Chuncheon 200-701 (Korea, Republic of); Cho, Young-Wook [Korea Basic Science Institute, Chuncheon Center, Gangwondaehak-gil 1, Chuncheon 200-701 (Korea, Republic of); Kim, Byung-Chul, E-mail: bckim@kangwon.ac.kr [Department of Biochemistry, College of Natural Sciences, Kangwon National University, 192-1 Hyoja-2-dong, Chuncheon 200-701 (Korea, Republic of)

2012-04-06

Highlights: Black-Right-Pointing-Pointer We examine the antiapoptotic mechanisms of Cdc25A. Black-Right-Pointing-Pointer Smad7 decreases the phosphorylation of I{kappa}B-alpha at Ser-32. Black-Right-Pointing-Pointer Smad7 positively regulates NF-{kappa}B activity through I{kappa}B-alpha ubiquitination. -- Abstract: Cell division cycle 25A (Cdc25A), a dual specificity protein phosphatase, exhibits anti-apoptotic activity, but the underlying molecular mechanisms are poorly characterized. Here we report that Cdc25A inhibits cisplatin-induced apoptotic cell death by stimulating nuclear factor-kappa B (NF-{kappa}B) activity. In HEK-293 cells, Cdc25A decreased protein level of inhibitor subunit kappa B alpha (I{kappa}-B{alpha}) in association with increased serine 32-phosphorylation, followed by stimulation of transcriptional activity of NF-{kappa}B. Inhibition of NF-{kappa}B activity by chemical inhibitor or overexpression of I{kappa}-B{alpha} in Cdc25A-elevated cancer cells resistant to cisplatin improved their sensitivity to cisplatin-induced apoptosis. Our data show for the first time that Cdc25A has an important physiological role in NF-{kappa}B activity regulation and it may be an important survival mechanism of cancer cells.

Is NF-kappaB a good target for cancer therapy? Hopes and pitfalls.

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Baud, Véronique; Karin, Michael

2009-01-01

Nuclear factor kappaB (NF-kappaB) transcription factors have a key role in many physiological processes such as innate and adaptive immune responses, cell proliferation, cell death, and inflammation. It has become clear that aberrant regulation of NF-kappaB and the signalling pathways that control its activity are involved in cancer development and progression, as well as in resistance to chemotherapy and radiotherapy. This article discusses recent evidence from cancer genetics and cancer genome studies that support the involvement of NF-kappaB in human cancer, particularly in multiple myeloma. The therapeutic potential and benefit of targeting NF-kappaB in cancer, and the possible complications and pitfalls of such an approach, are explored.

NF-kappaB signaling mediates vascular smooth muscle endothelin type B receptor expression in resistance arteries

DEFF Research Database (Denmark)

Zheng, Jian-Pu; Zhang, Yaping; Edvinsson, Lars

2010-01-01

Vascular smooth muscle cells (SMC) endothelin type B (ET(B)) receptor upregulation results in strong vasoconstriction and reduction of local blood flow. We hypothesizes that the underlying molecular mechanisms involve transcriptional factor nuclear factor-kappaB (NF-kappaB) pathway. ET(B) recepto...

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

Ultraviolet B Radiation Stimulates the Interaction between Nuclear Factor of Activated T Cells 5 (NFAT5) and Nuclear Factor-Kappa B (NF-κB) in Human Lens Epithelial Cells.

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Chung, Inyoung; Hah, Young-Sool; Ju, SunMi; Kim, Ji-Hye; Yoo, Woong-Sun; Cho, Hee-Young; Yoo, Ji-Myong; Seo, Seong-Wook; Choi, Wan-Sung; Kim, Seong-Jae

2017-07-01

Nuclear factor-kappa B (NF-κB) has been proposed as a therapeutic target for the treatment of cataracts. The authors investigated the relationship between nuclear factor of activated T cells 5 (NFAT5) and NF-κB in ultraviolet B (UVB)-irradiated human lens epithelial (HLE) cells. Human lens epithelial B-3 (HLE-B3) cells were exposed to UVB light at a dose of 10 mJ/cm 2 and then incubated for 24 h. Cell viability was assessed by using the Cell Counting Kit-8 (CCK-8) assay. Gene expression level of NFAT5 was determined using real-time quantitative polymerase chain reaction (qPCR). Protein expression levels of NFAT5, NF-κB p65, and α-smooth muscle actin (α-SMA) and the association of NFAT5 with the NF-κB p65 subunit were measured by Western blot analysis and a co-immunoprecipitation assay, respectively. The cellular distribution of NFAT5 and NF-κB p65 was examined by triple immunofluorescence staining. At 24 h after UVB exposure, cell viability significantly decreased in a dose-dependent manner, and UVB light (15 and 20 mJ/cm 2 ) significantly increased the ROS generation. UVB irradiation increased NFAT5 mRNA and protein levels and increased phosphorylation of NF-κB in HLE-B3 cells. α-SMA protein levels were increased in the irradiated cells. In addition, NFAT5 and NF-κB translocated from the cytoplasm to the nucleus, and binding between the p65 subunit and NFAT5 was increased. Exposure to UVB radiation induces nuclear translocation and stimulates binding between NFAT5 and NF-κB proteins in HLE-B3 cells. These interactions may form part of the biochemical mechanism of cataractogenesis in UVB-irradiated HLECs.

Hemin inhibits cyclooxygenase-2 expression through nuclear factor-kappa B activation and ornithine decarboxylase expression in 12-O-tetradecanoylphorbol-13-acetate-treated mouse skin

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Park, Jae Hee; Lee, Chang Ki [Department of Oral Biology, Yonsei University College of Dentistry, 134 Shinchon-Dong, Seodaemoon-Ku, Seoul 120-752 (Korea, Republic of); Oral Cancer Research Institute, Yonsei University College of Dentistry, 134 Shinchon-Dong, Seodaemoon-Ku, Seoul 120-752 (Korea, Republic of); Hwang, Young Sun [Department of Applied Life Science and Brain Korea 21 Project, Yonsei University College of Dentistry, 134 Shinchon-Dong, Seodaemoon-Ku, Seoul 120-752 (Korea, Republic of); Park, Kwang-Kyun [Department of Oral Biology, Yonsei University College of Dentistry, 134 Shinchon-Dong, Seodaemoon-Ku, Seoul 120-752 (Korea, Republic of); Department of Applied Life Science and Brain Korea 21 Project, Yonsei University College of Dentistry, 134 Shinchon-Dong, Seodaemoon-Ku, Seoul 120-752 (Korea, Republic of); Chung, Won-Yoon [Department of Oral Biology, Yonsei University College of Dentistry, 134 Shinchon-Dong, Seodaemoon-Ku, Seoul 120-752 (Korea, Republic of); Department of Applied Life Science and Brain Korea 21 Project, Yonsei University College of Dentistry, 134 Shinchon-Dong, Seodaemoon-Ku, Seoul 120-752 (Korea, Republic of)], E-mail: wychung@yuhs.ac

2008-07-03

Inflammation induced by various stimuli has been found to be associated with increased risk for most types of human cancer. Inflammation facilitates the initiation of normal cells, as well as the growth of initiated cells and their progression to malignancy through production of proinflammatory cytokines and diverse reactive oxygen/nitrogen species. These also activate the signaling molecules that are involved in inflammation and carcinogenesis. Our previous studies have demonstrated that hemin inhibited 7,12-dimethylbenz[a]anthracene (DMBA)-induced bacterial mutagenesis and oxidative DNA damage, reduced the level of DNA-DMBA adduct and 12-O-tetradecanoylphorobl-13-acetate (TPA)-induced tumor formation in DMBA-initiated ICR mouse skin, and inhibited myeloperoxidase and ornithine decarboxylase (ODC) activity and H{sub 2}O{sub 2} formation in TPA-treated mouse skin. In the present study, to further elucidate the molecular mechanisms underlying the chemopreventive activity of hemin, its effect on the expression of ODC and cyclooxygenase (COX)-2, and the activation of nuclear factor-kappa B (NF-{kappa}B) and mitogen-activated protein kinases (MAPKs) regulating these proteins were explored in mouse skin with TPA-induced inflammation. Topically applied hemin inhibited ear edema and epidermal thickness in mice treated with TPA. Pretreatment with hemin reduced the expression of ODC and COX-2, and also reduced NF-{kappa}B activation in TPA-stimulated mouse skin. In addition, hemin suppressed the TPA-induced activation of extracellular signal-regulated protein kinase (ERK) and p38 MAPK in a dose-dependent manner. Taken together, hemin inhibited TPA-induced COX-2 expression by altering NF-{kappa}B signaling pathway via ERK and p38 MAPK, as well as TPA-induced ODC expression in mouse skin. Thereby, hemin may be an attractive candidate for a chemopreventive agent.

Nuclear Factor kappa B is required for the production of infectious human herpesvirus 8 virions

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Negin N Blattman

2014-04-01

Full Text Available Human herpesvirus 8 (HHV8 infection leads to potent activation of nuclear factor kappa B (NFB in primary and transformed cells. We used recombinant HHV8 (rKSHV.219 expressing green fluorescent protein under the constitutive cellular promoter elongation factor 2 and red fluorescent protein under an early HHV8 lytic gene promoter T1.1, to monitor replication during infection of human foreskin fibroblasts (HF, noting changes in NFB activity. In primary HF, NFB levels do not affect HHV8 ability to establish infection or maintain latency. Furthermore, there was no effect on the percent of cells undergoing reactivation from latency, and there were similar numbers of released and cell associated HHV8 viral particles following reactivation in the presence of inhibitors. Reactivation of HHV8 in latently infected HF in the presence of NFB inhibitors resulted in production of viral particles that did not efficiently establish infection, due to deficiencies in binding and/or entry into normally permissive cells. Exogenous expression of glycoprotein M, an envelope protein involved in viral binding and entry was able to partially overcome the deficiency induced by NFB inhibitors. Our data indicate that in primary cells, NFB is not required for infection, establishment of latency, or entry into the lytic cycle, but is required for the expression of virion associated genes involved in the initial steps of virion infectivity. These studies suggest that strategies to inhibit NFB may prevent HHV8 spread and should be considered as a potential therapeutic target for preventing HHV8 associated diseases.

A critique on nuclear factor-kappa B and signal transducer and activator of transcription 3: The key transcription factors in periodontal pathogenesis

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Ranjith Ambili

2017-01-01

Full Text Available Periodontal disease is initiated by microorganisms in dental plaque, and host immunoinflammatory response to the microbial challenge helps in disease progression. Conventional periodontal therapy was mainly targeted on the elimination of microbial component. However, a better understanding of molecular aspects in host response will enable the clinicians to formulate effective host modulation therapy (HMT for the periodontal management. Inflammatory mediators were the main targets for HMT in the past. Transcription factors can regulate the production of multiple mediators simultaneously, and inhibition of these factors will be more beneficial than blocking individual molecule. Two important transcription factors implicated in chronic inflammatory diseases are nuclear factor kappa B (NF-κB and signal transducers and activators of transcription 3. The role of these factors in periodontal disease is a less explored area. This comprehensive review is aimed at unveiling the critical role of NF-κB and signal transducers and activators of transcription 3 in periodontal pathogenesis. An online search was performed using MEDLINE/PubMed database. All publications till 2016 related to NF-κB, signal transducer and activator of transcription 3 (STAT3, and inflammation were included in writing this review. A total of 27,390 references were published based on the search terms used. Out of these, 507 were related to the periodontal research published in English till 2016. Relevant papers were chosen after carefully reading the abstract. This review has attempted to comprehend the existing knowledge regarding the role of transcription factors NF-κB and STAT3 in periodontal disease. Moreover, it also provides a connecting molecular link for the periodontal medicine concept.

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

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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

NF-kappaB and p53 are the dominant apoptosis-inducing transcription factors elicited by the HIV-1 envelope.

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Perfettini, Jean-Luc; Roumier, Thomas; Castedo, Maria; Larochette, Nathanael; Boya, Patricia; Raynal, Brigitte; Lazar, Vladimir; Ciccosanti, Fabiola; Nardacci, Roberta; Penninger, Josef; Piacentini, Mauro; Kroemer, Guido

2004-03-01

The coculture of cells expressing the HIV-1 envelope glycoprotein complex (Env) with cells expressing CD4 results into cell fusion, deregulated mitosis, and subsequent cell death. Here, we show that NF-kappaB, p53, and AP1 are activated in Env-elicited apoptosis. The nuclear factor kappaB (NF-kappaB) super repressor had an antimitotic and antiapoptotic effect and prevented the Env-elicited phosphorylation of p53 on serine 15 and 46, as well as the activation of AP1. Transfection with dominant-negative p53 abolished apoptosis and AP1 activation. Signs of NF-kappaB and p53 activation were also detected in lymph node biopsies from HIV-1-infected individuals. Microarrays revealed that most (85%) of the transcriptional effects of HIV-1 Env were blocked by the p53 inhibitor pifithrin-alpha. Macroarrays led to the identification of several Env-elicited, p53-dependent proapoptotic transcripts, in particular Puma, a proapoptotic "BH3-only" protein from the Bcl-2 family known to activate Bax/Bak. Down modulation of Puma by antisense oligonucleotides, as well as RNA interference of Bax and Bak, prevented Env-induced apoptosis. HIV-1-infected primary lymphoblasts up-regulated Puma in vitro. Moreover, circulating CD4+ lymphocytes from untreated, HIV-1-infected donors contained enhanced amounts of Puma protein, and these elevated Puma levels dropped upon antiretroviral therapy. Altogether, these data indicate that NF-kappaB and p53 cooperate as the dominant proapoptotic transcription factors participating in HIV-1 infection.

Impedimetric aptasensor for nuclear factor kappa B with peroxidase-like mimic coupled DNA nanoladders as enhancer.

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Peng, Kanfu; Zhao, Hongwen; Xie, Pan; Hu, Shuang; Yuan, Yali; Yuan, Ruo; Wu, Xiongfei

2016-07-15

In this work, we developed a sensitive and universal aptasensor for nuclear factor kappa B (NF-κB) detection based on peroxidase-like mimic coupled DNA nanoladders for signal amplification. The dsDNA formed by capture DNA S1 and NF-κB binding aptamer (NBA) was firstly assembled on electrode surface. The presence of target NF-κB then led to the leave of NBA from electrode surface and thus provided the binding sites for immobilizing initiator to trigger in situ formation of DNA nanoladders on electrode surface. Since the peroxidase-like mimic manganese (III) meso-tetrakis (4-Nmethylpyridyl)-porphyrin (MnTMPyP) interacts with DNA nanoladders via groove binding, the insoluble benzo-4-chlorohexadienone (4-CD) precipitation derived from the oxidation of 4-chloro-1-naphthol (4-CN) could be formed on electrode surface in the presence of H2O2, resulting in a significantly amplified EIS signal output for quantitative target analysis. As a result, the developed aptasensor showed a low detection limit of 7pM and a wide linear range of 0.01-20nM. Featured with high sensitivity and label-free capability, the proposed sensing scheme can thus offer new opportunities for achieving sensitive, selective and stable detection of different types of target proteins. Copyright © 2016 Elsevier B.V. All rights reserved.

[Effects of TCM treatment according to syndrome differentiation on expressions of nuclear factor-kappaB and gamma-glutamylcysteine synthetase in rats with chronic obstructive pulmonary disease of various syndrome types].

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Zhang, Wei; Zhang, Xin-Yue; Shao, Yu-Meng

2007-05-01

To explore the mechanism of traditional Chinese medicine (TCM) treatment according to syndrome differentiation in treating chronic obstructive pulmonary disease (COPD) by observing the changes of nuclear factor-kappaB (NF-kappaB) and gamma-glutamylcysteine synthetase (gamma-GCS) expression levels in rats. COPD model was established by modified method of combining fumigation and lipopolysaccharide (LPS) intra-tracheal dripping. Model rats were treated respectively for succesive 14 days according to their syndrome, that is, Xiaoqinglong Decoction to the rats of cold-phlegm accumulation in Fei, Maxing Shigan Decoction to those of heat-phlegm accumulation in Fei, Yupingfeng Decoction to those of Fei-qi deficiency, Liujunzi Decoction to those of Pi-qi deficiency, Renshen Gejie Decoction to those of Shen qi-deficiency. Besides, model rats in the model control group received 2mL normal saline daily, and no intervention was applied in the normal control group. The expression of gamma-GCS and NF-kappaB was detected by immunochemistry before and after treatment. Compared with that in the normal rats, the expressions of gamma-GCS and NF-kappaB in bronchial and alveolar epithelium of COPD rats before treatment were significantly higher, but the positive expression rates were lowered after treatment significantly (Psyndrome differentiation could rectify imbalance of oxidation/anti-oxidation and alleviate inflammatory reaction in COPD rats, thus to treat COPD effectively.

Antiinflammatory Activity of Gynura bicolor (紅鳳菜 Hóng Fèng Cài Ether Extract Through Inhibits Nuclear Factor Kappa B Activation

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Chih-Chung Wu

2013-01-01

Full Text Available This study investigated effects of the Gynura bicolor (Roxb. and Willd. DC. ether extract (GBEE on nitric oxide (NO and prostaglandin (PGE2 production on the lipopolysaccharide (LPS-induced inflammatory response in RAW 264.7 cells. A composition analysis of GBEE showed that the major compounds were b-carotene, chlorophyll, and quercetin, respectively. Furthermore, NO and PGE2 levels of 120 μg/ml GBEE-treated cells were 70% and 9.8%, respectively, than those of cells treated with LPS alone. Immunoblots assays showed that the GBEE dose-dependently suppressed LPS-induced inducible NO synthase (iNOS and cyclooxygenase (COX-2 protein levels. The GBEE significantly decreased cytosolic phosphorylated (p-IκBa and nuclear p65 protein expressions. Electrophoresis mobility shift assays indicated that the GBEE effectively inhibited nuclear factor kappa B (NF-κB activation induced by LPS. These results support a role of the GBEE in suppressing activation of NF-κB to inhibit NO and PGE2 production in the LPS-induced inflammatory response by RAW 264.7 cells.

Memory extinction entails the inhibition of the transcription factor NF-kappaB.

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Emiliano Merlo

Full Text Available In contextual memories, an association between a positive or negative reinforcement and the contextual cues where the reinforcement occurs is formed. The re-exposure to the context without reinforcement can lead to memory extinction or reconsolidation, depending on the number of events or duration of a single event of context re-exposure. Extinction involves the temporary waning of the previously acquired conditioned response. The molecular processes underlying extinction and the mechanisms which determine if memory will reconsolidate or extinguish after retrieval are not well characterized, particularly the role of transcription factors and gene expression. Here we studied the participation of a transcription factor, NF-kappaB, in memory extinction. In the crab context-signal memory, the activation of NF-kappaB plays a critical role in consolidation and reconsolidation, memory processes that are well characterized in this model. The administration of a NF-kappaB inhibitor, sulfasalazine prior to extinction session impeded spontaneous recovery. Moreover, reinstatement experiments showed that the original memory was not affected and that NF-kappaB inhibition by sulfasalazine impaired spontaneous recovery strengthening the ongoing memory extinction process. Interestingly, in animals with fully consolidated memory, a brief re-exposure to the training context induced neuronal NF-kappaB activation and reconsolidation, while prolonged re-exposure induced NF-kappaB inhibition and memory extinction. These data constitutes a novel insight into the molecular mechanisms involved in the switch between memory reconsolidation and extinction. Moreover, we propose the inhibition of NF-kappaB as the engaged mechanism underlying extinction, supporting a novel approach for the pharmacological enhancement of this memory process. The accurate description of the molecular mechanisms that support memory extinction is potentially useful for developing new strategies

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.

A novel electrochemical approach for nuclear factor kappa B detection based on triplex DNA and gold nanoparticles

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Shen Min; Yang Mei; Li Hao; Liang Zhiqiang; Li Genxi

2012-01-01

Highlights: ► A simple, selective, and sensitive electrochemical NF-κB sensor was presented. ► NF-κB was precisely qualified by chronocoulometry with a detection limit of 0.13 nM. ► NF-κB was also successfully detected in contaminated samples by our approach. - Abstract: The transcription factor nuclear factor kappa B (NF-κB) is always a standard for inducible transcription factors, while nearly all NF-κB studies require the measurement of the level of activated NF-κB in cells. Herein we report a novel electrochemical approach for accurate detection of NF-κB with the help of triplex DNA and gold nanoparticles (AuNPs). Firstly, double-stranded DNA (dsDNA) molecules are self-assembled on the surface of a gold electrode. Then, AuNPs are functionalized with triplex-forming oligonucleotide (TFO). Since TFO may act with the dsDNA to form triplex DNA, the TFO functionalized on the AuNPs surfaces will bind with the dsDNA immobilized on the electrode surface, bringing large amounts of electrochemical compounds [Ru(NH 3 ) 6 ] 3+ close to the electrode to generate an intense electrochemical signal. However, in the presence of NF-κB, the protein will capture and bind with the dsDNA to replace TFO–AuNPs, resulting in significant decrease of electrochemical signal of [Ru(NH 3 ) 6 ] 3+ . By using this “on-off” strategy, NF-κB has been quantified in the range from 0.4 to 12.0 nM, with a detection limit of 0.13 nM. This approach has also been successfully used to detect NF-κB in contaminated samples with high specificity.

Purinergic signaling is required for fluid shear stress-induced NF-{kappa}B translocation in osteoblasts

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Genetos, Damian C., E-mail: dgenetos@ucdavis.edu [Department of Anatomy, Cell Biology, and Physiology, School of Veterinary Medicine, University of California, Davis, CA (United States); Karin, Norman J. [Cell Biology and Biochemistry, Pacific Northwest National Laboratory, Richland, WA (United States); Geist, Derik J. [Department of Orthopaedic Surgery, Indiana University School of Medicine, Indianapolis, IN (United States); Donahue, Henry J. [Division of Musculoskeletal Sciences, Department of Orthopaedics and Rehabilitation, Pennsylvania State College of Medicine, Hershey, PA (United States); Duncan, Randall L. [Department of Orthopaedic Surgery, Indiana University School of Medicine, Indianapolis, IN (United States)

2011-04-01

Fluid shear stress regulates gene expression in osteoblasts, in part by activation of the transcription factor NF-{kappa}B. We examined whether this process was under the control of purinoceptor activation. MC3T3-E1 osteoblasts under static conditions expressed the NF-{kappa}B inhibitory protein I{kappa}B{alpha} and exhibited cytosolic localization of NF-{kappa}B. Under fluid shear stress, I{kappa}B{alpha} levels decreased, and concomitant nuclear localization of NF-{kappa}B was observed. Cells exposed to fluid shear stress in ATP-depleted medium exhibited no significant reduction in I{kappa}B{alpha}, and NF-{kappa}B remained within the cytosol. Similar results were found using oxidized ATP or Brilliant Blue G, P2X{sub 7} receptor antagonists, indicating that the P2X{sub 7} receptor is responsible for fluid shear-stress-induced I{kappa}B{alpha} degradation and nuclear accumulation of NF-{kappa}B. Pharmacologic blockage of the P2Y6 receptor also prevented shear-induced I{kappa}B{alpha} degradation. These phenomena involved neither ERK1/2 signaling nor autocrine activation by P2X{sub 7}-generated lysophosphatidic acid. Our results suggest that fluid shear stress regulates NF-{kappa}B activity through the P2Y{sub 6} and P2X{sub 7} receptor.

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

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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.

Pharmacological Inhibition of Macrophage Toll-like Receptor 4/Nuclear Factor-kappa B Alleviates Rhabdomyolysis-induced Acute Kidney Injury.

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Huang, Rong-Shuang; Zhou, Jiao-Jiao; Feng, Yu-Ying; Shi, Min; Guo, Fan; Gou, Shen-Ju; Salerno, Stephen; Ma, Liang; Fu, Ping

2017-09-20

Acute kidney injury (AKI) is the most common and life-threatening systemic complication of rhabdomyolysis. Inflammation plays an important role in the development of rhabdomyolysis-induced AKI. This study aimed to investigate the kidney model of AKI caused by rhabdomyolysis to verify the role of macrophage Toll-like receptor 4/nuclear factor-kappa B (TLR4/NF-κB) signaling pathway. C57BL/6 mice were injected with a 50% glycerin solution at bilateral back limbs to induce rhabdomyolysis, and CLI-095 or pyrrolidine dithiocarbamate (PDTC) was intraperitoneally injected at 0.5 h before molding. Serum creatinine levels, creatine kinase, the expression of tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6, and hematoxylin and eosin stainings of kidney tissues were tested. The infiltration of macrophage, mRNA levels, and protein expression of TLR4 and NF-κB were investigated by immunofluorescence double-staining techniques, reverse transcriptase-quantitative polymerase chain reaction, and Western blotting, respectively. In vitro, macrophage RAW264.7 was stimulated by ferrous myoglobin; the cytokines, TLR4 and NF-κB expressions were also detected. In an in vivo study, using CLI-095 or PDTC to block TLR4/NF-κB, functional and histologic results showed that the inhibition of TLR4 or NF-κB alleviated glycerol-induced renal damages (P rhabdomyolysis-induced AKI by the regulation of proinflammatory cytokine production and macrophage infiltration.

Immunotoxicity of ochratoxin A and aflatoxin B1 in combination is associated with the nuclear factor kappa B signaling pathway in 3D4/21 cells.

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Hou, Lili; Gan, Fang; Zhou, Xuan; Zhou, Yajiao; Qian, Gang; Liu, Zixuan; Huang, Kehe

2018-05-01

The co-contamination of cereals, grains, crops, and animal feeds by mycotoxins is a universal problem. Humans and animals are exposed to several mycotoxins simultaneously as evidenced by extensive studies on this topic. Yet, most studies have addressed the effects of mycotoxins individually. Aflatoxin B1 and ochratoxin A can induce immunotoxicity. However, it remains unclear whether a combination of these mycotoxins aggravates immunotoxicity and the potential mechanism underlying this effect. In this study, we used the cell line 3D4/21, swine alveolus macrophages and innate immune cell. The results showed that the percentage of cell inhibition, annexin V/PI-positive rates, and the expression of pro-inflammatory cytokines (tumor necrosis factor alpha and interleukin-6) significantly increased and the release of lactate dehydrogenase and phagocytotic index were significantly decreased at different concentrations of aflatoxin B1 and ochratoxin A combination when compared with control. The combination of aflatoxin B1 and ochratoxin A significantly decreased the production of GSH and increased reactive oxygen species level. However, N-acetylcysteine suppressed the oxidative stress and alleviated the immunotoxicity induced by the combination. The combination of aflatoxin B1 and ochratoxin A markedly enhanced the degradation of IκBa, the phosphorylation of nuclear factor kappa B (p65), and the translocation of activated nuclear factor kappa B (NF-κB) into the nuclei as demonstrated by western blotting and confocal laser scanning microscopy. These effects could be reversed by BAY 11-7082, a specific inhibitor of NF-κB. Taken together, a combination of aflatoxin B1 and ochratoxin A could aggravate immunotoxicity by activating the NF-κB signaling pathway. Copyright © 2018 Elsevier Ltd. All rights reserved.

Chalepin: A Compound from Ruta angustifolia L. Pers Exhibits Cell Cycle Arrest at S phase, Suppresses Nuclear Factor-Kappa B (NF-κB) Pathway, Signal Transducer and Activation of Transcription 3 (STAT3) Phosphorylation and Extrinsic Apoptotic Pathway in Non-small Cell Lung Cancer Carcinoma (A549).

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Richardson, Jaime Stella Moses; Aminudin, Norhaniza; Abd Malek, Sri Nurestri

2017-10-01

Plants have been a major source of inspiration in developing novel drug compounds in the treatment of various diseases that afflict human beings worldwide. Ruta angustifolia L. Pers known locally as Garuda has been conventionally used for various medicinal purposes such as in the treatment of cancer. A dihydrofuranocoumarin named chalepin, which was isolated from the chloroform extract of the plant, was tested on its ability to inhibit molecular pathways of human lung carcinoma (A549) cells. Cell cycle analysis and caspase 8 activation were conducted using a flow cytometer, and protein expressions in molecular pathways were determined using Western blot technique. Cell cycle analysis showed that cell cycle was arrested at the S phase. Further studies using Western blotting technique showed that cell cycle-related proteins such as cyclins, cyclin-dependent kinases (CDKs), and inhibitors of CDKs correspond to a cell cycle arrest at the S phase. Chalepin also showed inhibition in the expression of inhibitors of apoptosis proteins. Nuclear factor-kappa B (NF-κB) pathway, signal transducer and activation of transcription 3 (STAT-3), cyclooxygenase-2, and c-myc were also downregulated upon treatment with chalepin. Chalepin was found to induce extrinsic apoptotic pathway. Death receptors 4 and 5 showed a dramatic upregulation at 24 h. Analysis of activation of caspase 8 with the flow cytometer showed an increase in activity in a dose- and time-dependent manner. Activation of caspase 8 induced cleavage of BH3-interacting domain death agonist, which initiated a mitochondrial-dependent or -independent apoptosis. Chalepin causes S phase cell cycle arrest, NF-κB pathway inhibition, and STAT-3 inhibition, induces extrinsic apoptotic pathway, and could be an excellent chemotherapeutic agent. This study reports the capacity of an isolated bioactive compound known as chalepin to suppress the nuclear factor kappa-light-chain-enhancer of activated B cells pathway, signal

Mineral trioxide aggregate promotes the odonto/osteogenic differentiation and dentinogenesis of stem cells from apical papilla via nuclear factor kappa B signaling pathway.

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Yan, Ming; Wu, Jintao; Yu, Yan; Wang, Yanping; Xie, Lizhe; Zhang, Guangdong; Yu, Jinhua; Zhang, Chengfei

2014-05-01

Mineral trioxide aggregate (MTA) has been widely used in clinical apexification and apexogenesis. However, the effects of MTA on the stem cells from apical papilla (SCAPs) and the precise mechanism of apexogenesis have not been elucidated in detail. Multiple colony-derived stem cells were isolated from the apical papillae, and the effects of MTA on the proliferation and differentiation of SCAPs were investigated both in vitro and in vivo. Activation of nuclear factor kappa B (NFκB) pathway in MTA-treated SCAPs was analyzed by immunofluorescence assay and Western blot. MTA at the concentration of 2 mg/mL did not affect the proliferation activity of SCAPs. However, 2 mg/mL MTA-treated SCAPs presented the ultrastructural changes, up-regulated alkaline phosphatase, increased calcium deposition, up-regulated expression of odontoblast markers (dentin sialoprotein and dentin sialophosphoprotein) and odonto/osteoblast markers (runt-related transcription factor 2 and osteocalcin), suggesting that MTA enhanced the odonto/osteoblastic differentiation of SCAPs in vitro. In vivo results confirmed that MTA can promote the regular dentinogenesis of SCAPs. Moreover, MTA-treated SCAPs exhibited the up-regulated cytoplasmic phos-IκBα and phos-P65, enhanced nuclear P65, and increased nuclear translocation of P65. When co-treated with BMS345541 (the specific NFκB inhibitor), MTA-mediated odonto/osteoblastic differentiation was significantly attenuated. MTA at the concentration of 2 mg/mL can improve the odonto/osteogenic capacity of SCAPs via the activation of NFκB pathway. Copyright © 2014 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Aconitum pseudo-laeve var. erectum Inhibits Receptor Activator of Nuclear Factor Kappa-B Ligand-Induced Osteoclastogenesis via the c-Fos/nuclear Factor of Activated T-Cells, Cytoplasmic 1 Signaling Pathway and Prevents Lipopolysaccharide-Induced Bone Loss in Mice

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Jong Min Baek

2014-08-01

Full Text Available Aconitum pseudo-laeve var. erectum (APE has been widely shown in herbal medicine to have a therapeutic effect on inflammatory conditions. However, there has been no evidence on whether the extract of APE is involved in the biological bone metabolism process, particularly osteoclast-mediated bone resorption. In this study, we confirmed that the administration of APE could restore normal skeletal conditions in a murine model of lipopolysaccharide (LPS-induced bone loss via a decrease in the receptor activator of nuclear factor kappa-B ligand (RANKL/osteoprotegerin (OPG ratio and osteoclast number. We then investigated the effect of APE on the RANKL-induced formation and function of osteoclasts to elucidate its underlying molecular mechanisms. APE suppressed the formation of tartrate-resistant acid phosphatase (TRAP-positive cells, as well as the bone-resorbing activity of mature osteoclasts. Furthermore, APE attenuated nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1 and c-Fos without affecting any early signal pathway of osteoclastogenesis. Subsequently, APE significantly downregulated the expression of various genes exclusively expressed in osteoclasts. These results demonstrate that APE restores LPS-induced bone loss through a decrease of the serum RANKL/OPG ratio, and inhibits osteoclast differentiation and function, suggesting the promise of APE as a potential cure for various osteoclast-associated bone diseases.

Protective protein/cathepsin A down-regulates osteoclastogenesis by associating with and degrading NF-kappaB p50/p65.

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Masuhara, Masaaki; Sato, Takuya; Hada, Naoto; Hakeda, Yoshiyuki

2009-01-01

Disruption of the cooperative function balance between osteoblasts and osteoclasts causes various bone disorders, some of which are attributed to abnormal osteoclast recruitment. Osteoclast differentiation is dependent on the receptor activator of nuclear factor (NF)-kappaB ligand (RANKL) as well as the macrophage colony-stimulating factor. The osteoclast formation induced by cytokines requires activation of NF-kappaB, AP-1 and nuclear factor of activated T cells c1. However, osteoclasts are not the only cell types that express these transcription factors, suggesting that some unknown molecules specific for osteoclasts may associate with the transcription factors. Here, we explored the possibility of molecules binding directly to NF-kappaB and cloned protective protein/cathepsin A (PPCA) by yeast two-hybrid screening using a cDNA library of osteoclast precursors. Forced expression of PPCA with p50/p65 in HEK293 cells decreased both the level of p50/p65 proteins and the transcriptional activity. Abundant PPCA was detected in the lysosomes of the transfected HEK293 cells, but a small amount of this enzyme was also present in the cytosolic fraction. In addition, over-expression of PPCA caused the disappearance of p50/p65 in both the lysosomal and cytosolic fractions. PPCA was expressed throughout osteoclastogenesis, and the expression was slightly up-regulated by RANKL signaling. Knockdown of PPCA in osteoclast precursors with PPCA siRNA stimulated binding of nuclear proteins to oligonucleotides containing an NF-kappaB binding motif and increased osteoclastogenesis. Our present results indicate a novel role for PPCA in osteoclastogenesis via down-regulation of NF-kappaB activity and suggest a new function for PPCA as an NF-kappaB-degrading enzyme in addition to its known multifunctional properties.

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.

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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.

Role of nuclear factor kappa B and reactive oxygen species in the tumor necrosis factor-a-induced epithelial-mesenchymal transition of MCF-7 cells

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R. Dong

2007-08-01

Full Text Available The microenvironment of the tumor plays an important role in facilitating cancer progression and activating dormant cancer cells. Most tumors are infiltrated with inflammatory cells which secrete cytokines such as tumor necrosis factor-a (TNF-a. To evaluate the role of TNF-a in the development of cancer we studied its effects on cell migration with a migration assay. The migrating cell number in TNF-a -treated group is about 2-fold of that of the control group. Accordingly, the expression of E-cadherin was decreased and the expression of vimentin was increased upon TNF-a treatment. These results showed that TNF-a can promote epithelial-mesenchymal transition (EMT of MCF-7 cells. Further, we found that the expression of Snail, an important transcription factor in EMT, was increased in this process, which is inhibited by the nuclear factor kappa B (NFkB inhibitor aspirin while not affected by the reactive oxygen species (ROS scavenger N-acetyl cysteine. Consistently, specific inhibition of NFkB by the mutant IkBa also blocked the TNF-a-induced upregulation of Snail promoter activity. Thus, the activation of NFkB, which causes an increase in the expression of the transcription factor Snail is essential in the TNF-a-induced EMT. ROS caused by TNF-a seemed to play a minor role in the TNF-a-induced EMT of MCF-7 cells, though ROS per se can promote EMT. These findings suggest that different mechanisms might be responsible for TNF-a - and ROS-induced EMT, indicating the need for different strategies for the prevention of tumor metastasis induced by different stimuli.

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

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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.

Proteasome and NF-kappaB inhibiting phaeophytins from the green alga Cladophora fascicularis.

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Huang, Xinping; Li, Min; Xu, Bo; Zhu, Xiaobin; Deng, Zhiwei; Lin, Wenhan

2007-03-21

Chemical examination of the green alga Cladophora fascicularis resulted in the isolation and characterization of a new porphyrin derivative, porphyrinolactone (1), along with five known phaeophytins 2-6 and fourteen sterols and cycloartanes. The structure of 1 was determined on the basis of spectroscopic analyses and by comparison of its NMR data with those of known phaeophytins. Compounds 1-6 displayed moderate inhibition of tumor necrosis factor alpha (TNF-alpha) induced nuclear factor-kappaB (NF-kappaB) activation, while 2 and 4 displayed potential inhibitory activity toward proteasome chymotripsin-like activation. The primary structure-activity relationship was also discussed.

Topical Anti-Nuclear Factor-Kappa B Small Interfering RNA with Functional Peptides Containing Sericin-Based Hydrogel for Atopic Dermatitis

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Takanori Kanazawa

2015-09-01

Full Text Available The small interfering RNA (siRNA is suggested to offer a novel means of treating atopic dermatitis (AD because it allows the specific silencing of genes related to AD pathogenesis. In our previous study, we found that siRNA targeted against RelA, an important nuclear factor-kappa B (NF-κB subdomain, with functional peptides, showed therapeutic effects in a mouse model of AD. In the present study, to develop a topical skin application against AD, we prepared a hydrogel containing anti-RelA siRNA and functional peptides and determined the intradermal permeation and the anti-AD effects in an AD mouse model. We selected the silk protein, sericin (SC, which is a versatile biocompatible biomaterial to prepare hydrogel as an aqueous gel base. We found that the siRNA was more widely delivered to the site of application in AD-induced ear skin of mice after topical application via the hydrogel containing functional peptides than via the preparation without functional peptides. In addition, the ear thickness and clinical skin severity of the AD-induced mice treated with hydrogel containing anti-RelA siRNA with functional peptides improved more than that of mice treated with the preparation formulated with negative siRNA.

Inhibition of nuclear factor kappa-B signaling reduces growth in medulloblastoma in vivo

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Deckard Lindsey A

2011-04-01

Full Text Available Abstract Background Medulloblastoma is a highly malignant pediatric brain tumor that requires surgery, whole brain and spine irradiation, and intense chemotherapy for treatment. A more sophisticated understanding of the pathophysiology of medulloblastoma is needed to successfully reduce the intensity of treatment and improve outcomes. Nuclear factor kappa-B (NFκB is a signaling pathway that controls transcriptional activation of genes important for tight regulation of many cellular processes and is aberrantly expressed in many types of cancer. Methods To test the importance of NFκB to medulloblastoma cell growth, the effects of multiple drugs that inhibit NFκB, pyrrolidine dithiocarbamate, diethyldithiocarbamate, sulfasalazine, curcumin and bortezomib, were studied in medulloblastoma cell lines compared to a malignant glioma cell line and normal neurons. Expression of endogenous NFκB was investigated in cultured cells, xenograft flank tumors, and primary human tumor samples. A dominant negative construct for the endogenous inhibitor of NFκB, IκB, was prepared from medulloblastoma cell lines and flank tumors were established to allow specific pathway inhibition. Results We report high constitutive activity of the canonical NFκB pathway, as seen by Western analysis of the NFκB subunit p65, in medulloblastoma tumors compared to normal brain. The p65 subunit of NFκB is extremely highly expressed in xenograft tumors from human medulloblastoma cell lines; though, conversely, the same cells in culture have minimal expression without specific stimulation. We demonstrate that pharmacological inhibition of NFκB in cell lines halts proliferation and leads to apoptosis. We show by immunohistochemical stain that phosphorylated p65 is found in the majority of primary tumor cells examined. Finally, expression of a dominant negative form of the endogenous inhibitor of NFκB, dnIκB, resulted in poor xenograft tumor growth, with average tumor volumes

Preventative effect of OMZ-SPT on lipopolysaccharide-induced acute lung injury and inflammation via nuclear factor-kappa B signaling in mice

International Nuclear Information System (INIS)

Wang, Ting; Hou, Wanru; Fu, Zhou

2017-01-01

Acute lung injury (ALI) is an early pathophysiologic change in acute respiratory distress syndrome and its management can be challenging. Omalizumab (Xolair™) is a recombinant DNA-derived, humanized antibody. OMZ-SPT is a polypeptide on the heavy chain of omalizumab monoclonal antibody. Here, we found that intramuscular administration of OMZ-SPT significantly improved survival and attenuated lung inflammation in female C57BL/6 mice suffering from lipopolysaccharide (LPS)-induced ALI. We also demonstrated that OMZ-SPT can inhibit expression of the inflammatory cytokines tumor necrosis factor-α, interleukin-1β and interleukin-6 by ELISA in mice suffering from LPS-induced ALI and a mouse macrophage line (RAW264.7 cells). In addition, we showed that OMZ-SPT inhibited LPS-induced activation of nuclear factor-kappa B (NF-κB) signaling and total expression of NF-κB by western blotting. These data suggest that OMZ-SPT could be a novel therapeutic choice for ALI. - Highlights: • OMZ-SPT is a polypeptide on the heavy chain of omalizumab monoclonal antibody. • Omalizumab (Xolair™) have anti-inflammatory effects. • OMZ-SPT can inhibit inflammatory responses and lung injury in LPS-induced ALI mice. • Protective effect of OMZ-SPT on ALI is due to inhibition of NF-κB signaling. • OMZ-SPT could be a novel therapeutic choice for ALI.

Ghrelin ameliorates intestinal barrier dysfunction in experimental colitis by inhibiting the activation of nuclear factor-kappa B

International Nuclear Information System (INIS)

Cheng, Jian; Zhang, Lin; Dai, Weiqi; Mao, Yuqing; Li, Sainan; Wang, Jingjie; Li, Huanqing; Guo, Chuanyong; Fan, Xiaoming

2015-01-01

Aim: This study aimed to investigate the effect and underlying mechanism of ghrelin on intestinal barrier dysfunction in dextran sulfate sodium (DSS)-induced colitis. Methods and results: Acute colitis was induced in C57BL/6J mice by administering 2.5% DSS. Saline or 25, 125, 250 μg/kg ghrelin was administrated intraperitoneally (IP) to mice 1 day before colitis induction and on days 4, 5, and 6 after DSS administration. IP injection of a ghrelin receptor antagonist, [D-lys 3 ]-GHRP-6, was performed immediately prior to ghrelin injection. Ghrelin (125 or 250 μg/kg) could reduce the disease activity index, histological score, and myeloperoxidase activities in experimental colitis, and also prevented shortening of the colon. Ghrelin could prevent the reduction of transepithelial electrical resistance and tight junction expression, and bolstered tight junction structural integrity and regulated cytokine secretion. Ultimately, ghrelin inhibited nuclear factor kappa B (NF-κB), inhibitory κB-α, myosin light chain kinase, and phosphorylated myosin light chain 2 activation. Conclusions: Ghrelin prevented the breakdown of intestinal barrier function in DSS-induced colitis. The protective effects of ghrelin on intestinal barrier function were mediated by its receptor GHSR-1a. The inhibition of NF-κB activation might be part of the mechanism underlying the effects of ghrelin that protect against barrier dysfunction. - Highlights: • Ghrelin ameliorates intestinal barrier dysfunction in experimental colitis. • The effect of ghrelin is mediated by GHSR-1a. • Inhibition of NF-κB activation

Ghrelin ameliorates intestinal barrier dysfunction in experimental colitis by inhibiting the activation of nuclear factor-kappa B

Energy Technology Data Exchange (ETDEWEB)

Cheng, Jian; Zhang, Lin [Department of Gastroenterology, Jinshan Hospital of Fudan University, Shanghai (China); Dai, Weiqi [Department of Gastroenterology, Shanghai Tenth People' s Hospital, Tongji University, Shanghai (China); Mao, Yuqing [Department of Gastroenterology, Jinshan Hospital of Fudan University, Shanghai (China); Li, Sainan [Department of Gastroenterology, Shanghai Tenth People' s Hospital, Tongji University, Shanghai (China); Wang, Jingjie; Li, Huanqing [Department of Gastroenterology, Jinshan Hospital of Fudan University, Shanghai (China); Guo, Chuanyong [Department of Gastroenterology, Shanghai Tenth People' s Hospital, Tongji University, Shanghai (China); Fan, Xiaoming, E-mail: xiaomingfan57@sina.com [Department of Gastroenterology, Jinshan Hospital of Fudan University, Shanghai (China)

2015-02-27

Aim: This study aimed to investigate the effect and underlying mechanism of ghrelin on intestinal barrier dysfunction in dextran sulfate sodium (DSS)-induced colitis. Methods and results: Acute colitis was induced in C57BL/6J mice by administering 2.5% DSS. Saline or 25, 125, 250 μg/kg ghrelin was administrated intraperitoneally (IP) to mice 1 day before colitis induction and on days 4, 5, and 6 after DSS administration. IP injection of a ghrelin receptor antagonist, [D-lys{sup 3}]-GHRP-6, was performed immediately prior to ghrelin injection. Ghrelin (125 or 250 μg/kg) could reduce the disease activity index, histological score, and myeloperoxidase activities in experimental colitis, and also prevented shortening of the colon. Ghrelin could prevent the reduction of transepithelial electrical resistance and tight junction expression, and bolstered tight junction structural integrity and regulated cytokine secretion. Ultimately, ghrelin inhibited nuclear factor kappa B (NF-κB), inhibitory κB-α, myosin light chain kinase, and phosphorylated myosin light chain 2 activation. Conclusions: Ghrelin prevented the breakdown of intestinal barrier function in DSS-induced colitis. The protective effects of ghrelin on intestinal barrier function were mediated by its receptor GHSR-1a. The inhibition of NF-κB activation might be part of the mechanism underlying the effects of ghrelin that protect against barrier dysfunction. - Highlights: • Ghrelin ameliorates intestinal barrier dysfunction in experimental colitis. • The effect of ghrelin is mediated by GHSR-1a. • Inhibition of NF-κB activation.

Vitamin D inhibits the growth of and virulence factor gene expression by Porphyromonas gingivalis and blocks activation of the nuclear factor kappa B transcription factor in monocytes.

Science.gov (United States)

Grenier, D; Morin, M-P; Fournier-Larente, J; Chen, H

2016-06-01

Increasing evidence suggests that 1,25-dihydroxyvitamin D3 (1,25(OH)2 D3 ), a fat-soluble secosteroid hormone, has a positive impact on periodontal health through diverse mechanisms. The present study was aimed at investigating the effect of 1,25(OH)2 D3 on the growth of and virulence factor gene expression by the periodontopathogenic bacterium Porphyromonas gingivalis. The effect of 1,25(OH)2 D3 on P. gingivalis-mediated activation of nuclear factor kappa B (NF-κB) transcription factor in monocytes was also assessed. A broth microdilution assay was used to determine the antibacterial activity of 1,25(OH)2 D3 . The modulation of virulence factor gene expression in P. gingivalis was assessed by quantitative reverse transcription-polymerase chain reaction. NF-κB activation was assessed using a human monocytic cell line stably transfected with a luciferase reporter containing NF-κB binding sites. Minimal inhibitory concentrations of 1,25(OH)2 D3 against P. gingivalis ranged from 3.125 to 6.25 μg/mL. Moreover, a partial synergistic effect was observed when 1,25(OH)2 D3 was used in association with metronidazole. 1,25(OH)2 D3 attenuated the virulence of P. gingivalis by reducing the expression of genes coding for important virulence factors, including adhesins (fimA, hagA and hagB) and proteinases (rgpA, rgpB and kgp). 1,25(OH)2 D3 dose-dependently prevented P. gingivalis-induced NF-κB activation in a monocyte model. Our study suggested that 1,25(OH)2 D3 selectively inhibits the growth of and virulence factor gene expression by P. gingivalis, in addition to attenuating NF-κB activation by this periodontopathogen. This dual action on P. gingivalis and the inflammatory response of host cells may be of particular interest with a view to developing a novel and inexpensive preventive/therapeutic strategy. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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.

NF-kappaB is involved in SHetA2 circumvention of TNF-alpha resistance, but not induction of intrinsic apoptosis.

Science.gov (United States)

Chengedza, Shylet; Benbrook, Doris Mangiaracina

2010-03-01

Treatment of cancer with tumor necrosis factor-alpha (TNF-alpha) is hindered by resistance and toxicity. The flexible heteroarotinoid, SHetA2, sensitizes resistant ovarian cancer cells to TNF-alpha-induced extrinsic apoptosis, and also induces intrinsic apoptosis as a single agent. This study tested the hypothesis that nuclear factor-kappaB (NF-kappaB) is involved in SHetA2-regulated intrinsic and extrinsic apoptosis. SHetA2 inhibited basal and TNF-alpha-induced or hydrogen peroxide-induced NF-kappaB activity through counter-regulation of upstream kinase (IkappaB kinase) activity, inhibitor protein (IkappaB-alpha) phosphorylation, and p-65 NF-kappaB subunit nuclear translocation, but independently of reactive oxygen species generation. Ectopic over-expression of p-65, or treatment with TNF-alpha receptor 1 (TNFR1) small interfering RNA or a caspase-8 inhibitor, each attenuated synergistic apoptosis by SHetA2 and TNF-alpha, but did not affect intrinsic apoptosis caused by SHetA2. In conclusion, NF-kappaB repression is involved in SHetA2 circumvention of resistance to TNF-alpha-induced extrinsic apoptosis, but not in SHetA2 induction of intrinsic apoptosis.

Dendrobium moniliforme Exerts Inhibitory Effects on Both Receptor Activator of Nuclear Factor Kappa-B Ligand-Mediated Osteoclast Differentiation in Vitro and Lipopolysaccharide-Induced Bone Erosion in Vivo.

Science.gov (United States)

Baek, Jong Min; Kim, Ju-Young; Ahn, Sung-Jun; Cheon, Yoon-Hee; Yang, Miyoung; Oh, Jaemin; Choi, Min Kyu

2016-03-01

Dendrobium moniliforme (DM) is a well-known plant-derived extract that is widely used in Oriental medicine. DM and its chemical constituents have been reported to have a variety of pharmacological effects, including anti-oxidative, anti-inflammatory, and anti-tumor activities; however, no reports discuss the beneficial effects of DM on bone diseases such as osteoporosis. Thus, we investigated the relationship between DM and osteoclasts, cells that function in bone resorption. We found that DM significantly reduced receptor activator of nuclear factor kappa-B ligand (RANKL)-induced tartrate-resistant acid phosphatase (TRAP)-positive osteoclast formation; DM directly induced the down-regulation of c-Fos and nuclear factor of activated T cells c1 (NFATc1) without affecting other RANKL-dependent transduction pathways. In the later stages of osteoclast maturation, DM negatively regulated the organization of filamentous actin (F-actin), resulting in impaired bone-resorbing activity by the mature osteoclasts. In addition, micro-computed tomography (μ-CT) analysis of the murine model revealed that DM had a beneficial effect on lipopolysaccharide (LPS)-mediated bone erosion. Histological analysis showed that DM attenuated the degradation of trabecular bone matrix and formation of TRAP-positive osteoclasts in bone tissues. These results suggest that DM is a potential candidate for the treatment of metabolic bone disorders such as osteoporosis.

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

Directory of Open Access Journals (Sweden)

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.

[The expression and significance of receptor activator of nuclear factor kappaB ligand and osteoprotegerin in periapical cyst and periapical granuloma].

Science.gov (United States)

Zhang, Meihua; Yu, Yunzhi; Miao, Yu

2012-08-01

To investigate the expression of receptor activator of nuclear factor kappaB ligand (RANKL) and osteoprotegerin (OPG) in periapical cyst and periapical granuloma by comparison with the expression in the normal periodontal tissue as control, and to identify their functional mechanism in the bone destruction of periapical cyst and granuloma. 20 periapical cyst tissues (cyst group), 20 periapical granuloma tissues (granuloma group), and 20 normal periodontal tissues (control group) were collected respectively. Immunohistochemical technology was performed to detect the expression of RANKL and OPG in above three groups. In cyst group, granuloma group and control group, the expression of RANKL were 75.00 +/- 7.54, 68.40 +/- 6.74 and 29.40 +/- 2.46, respectively. The expression of OPG were 38.10 +/- 7.09, 47.65 +/- 13.85 and 58.60 +/- 5.88, respectively. The differences among the three groups were statistically significant (Pcysts group were negatively correlated (r=-0.56, P=0.01) and were not correlated with granuloma and control group (P>0.05). RANKL and OPG play roles in the bone absorption of periapical disease. In periapical disease, abnormal expression of RANKL and OPG are detected, RANKL significantly increase, OPG decrease, bone absorption accelerate and osteolytic lesion are observed. In periapical cyst, the bone absorption is more active compared with periapical granuloma.

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.

The Regulatory Role of Nuclear Factor Kappa B in the Heart of Hereditary Hypertriglyceridemic Rat

Czech Academy of Sciences Publication Activity Database

Vranková, S.; Barta, A.; Klimentová, J.; Dovinová, I.; Líšková, Silvia; Dobešová, Zdenka; Pecháňová, O.; Kuneš, Jaroslav; Zicha, Josef

2016-01-01

Roč. 2016, č. 2016 (2016), s. 9814038 ISSN 1942-0900 R&D Projects: GA MZd(CZ) NV15-25396A Institutional support: RVO:67985823 Keywords : nuclear factor-kB * nitric oxide * reactive oxygen species * heart * hereditary hypertriglyceridemic rats Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 4.593, year: 2016

Dose-rate effects of protons on in vivo activation of nuclear factor-kappa B and cytokines in mouse bone marrow cells

International Nuclear Information System (INIS)

Rithidech, K.N.; Rusek, A.; Reungpatthanaphong, P.; Honikel, L.; Simon, S.R.

2010-01-01

The objective of this study was to determine the kinetics of nuclear factor-kappa B (NF-κB) activation and cytokine expression in bone marrow (BM) cells of exposed mice as a function of the dose rate of protons. The cytokines included in this study are pro-inflammatory (i.e., tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β), and IL-6) and anti-inflammatory cytokines (i.e., IL-4 and IL-10). We gave male BALB/cJ mice a whole-body exposure to 0 (sham-controls) or 1.0 Gy of 100 MeV protons, delivered at 5 or 10 mGy min -1 , the dose and dose rates found during solar particle events in space. As a reference radiation, groups of mice were exposed to 0 (sham-controls) or 1 Gy of 137 Cs γ rays (10 mGy min -1 ). After irradiation, BM cells were collected at 1.5, 3, 24 h, and 1 month for analyses (five mice per treatment group per harvest time). The results indicated that the in vivo time course of effects induced by a single dose of 1 Gy of 100 MeV protons or 137 Cs γ rays, delivered at 10 mGy min -1 , was similar. Although statistically significant levels of NF-κB activation and pro-inflammatory cytokines in BM cells of exposed mice when compared to those in the corresponding sham controls (Student's t-test, p -1 induced significant levels of anti-inflammatory cytokines. The results indicate dose-rate effects of protons.

Diclofenac pretreatment effects on the toll-like receptor 4/nuclear factor kappa B-mediated inflammatory response to eccentric exercise in rat liver.

Science.gov (United States)

Barcelos, Rômulo Pillon; Bresciani, Guilherme; Rodriguez-Miguelez, Paula; Cuevas, Maria José; Soares, Félix Alexandre Antunes; Barbosa, Nilda Vargas; González-Gallego, Javier

2016-03-01

Acute exercise is a stress stimulus that may cause cell damage through the activation of the toll-like receptor (TLR)4 pathway, resulting in the translocation of nuclear factor kappa B (NF-κB) into the cell nucleus and the upregulation of inflammatory genes. Nonsteroidal anti-inflammatory drugs, such as diclofenac, are often prescribed to counteract exercise-induced inflammation. This study analyzed effects of diclofenac pretreatment on the TLR4/NF-κB pathway in rat liver after an acute eccentric exercise. Twenty male Wistar rats were divided in four groups: control-saline, control-diclofenac, exercise-saline and exercise-diclofenac. The rats received saline or diclofenac (10mg/kg) for 7days prior to an eccentric exercise bout. After exercise there was an increase in TLR4, myeloid differentiation primary response gene 88 (MyD88), TIR domain-containing adaptor inducing interferon (TRIF) and p65 NF-κB subunit protein levels. Exercise also resulted in increased mRNA and protein expression of interleukin (IL)-6, inducible nitric oxide synthase (iNOS) and tumor necrosis factor (TNF)-α. Proinflammatory effects of exercise were prevented by the administration of diclofenac, which blunted the activation of the TLR4/NF-κB pathway and the inflammatory response in the liver of exercised rats. Results from the present study highlight the role of TLR4 as a target for anti-inflammatory interventions. Copyright © 2016 Elsevier Inc. All rights reserved.

Insulin receptor substrate-3, interacting with Bcl-3, enhances p50 NF-{kappa}B activity

Energy Technology Data Exchange (ETDEWEB)

Kabuta, Tomohiro [Departments of Animal Sciences and Applied Biological Chemistry, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Tokyo 113-8657 (Japan); Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo 187-8502 (Japan); Hakuno, Fumihiko; Cho, Yoshitake; Yamanaka, Daisuke; Chida, Kazuhiro [Departments of Animal Sciences and Applied Biological Chemistry, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Tokyo 113-8657 (Japan); Asano, Tomoichiro [Graduate School of Biomedical Science, Hiroshima University, Hiroshima 734-8551 (Japan); Wada, Keiji [Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo 187-8502 (Japan); Takahashi, Shin-Ichiro, E-mail: atkshin@mail.ecc.u-tokyo.ac.jp [Departments of Animal Sciences and Applied Biological Chemistry, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Tokyo 113-8657 (Japan)

2010-04-09

The insulin receptor substrate (IRS) proteins are major substrates of both insulin receptor and insulin-like growth factor (IGF)-I receptor tyrosine kinases. Previously, we reported that IRS-3 is localized to both cytosol and nucleus, and possesses transcriptional activity. In the present study, we identified Bcl-3 as a novel binding protein to IRS-3. Bcl-3 is a nuclear protein, which forms a complex with the homodimer of p50 NF-{kappa}B, leading to enhancement of transcription through p50 NF-{kappa}B. We found that Bcl-3 interacts with the pleckstrin homology domain and the phosphotyrosine binding domain of IRS-3, and that IRS-3 interacts with the ankyrin repeat domain of Bcl-3. In addition, IRS-3 augmented the binding activity of p50 to the NF-{kappa}B DNA binding site, as well as the tumor necrosis factor (TNF)-{alpha}-induced transcriptional activity of NF-{kappa}B. Lastly, IRS-3 enhanced NF-{kappa}B-dependent anti-apoptotic gene induction and consequently inhibited TNF-{alpha}-induced cell death. This series of results proposes a novel function for IRS-3 as a transcriptional regulator in TNF-{alpha} signaling, distinct from its function as a substrate of insulin/IGF receptor kinases.

Assessment of hypoxia and TNF-alpha response by a vector with HRE and NF-kappaB response elements.

Science.gov (United States)

Chen, Zhilin; Eadie, Ashley L; Hall, Sean R; Ballantyne, Laurel; Ademidun, David; Tse, M Yat; Pang, Stephen C; Melo, Luis G; Ward, Christopher A; Brunt, Keith R

2017-01-01

Hypoxia and inflammatory cytokine activation (H&I) are common processes in many acute and chronic diseases. Thus, a single vector that responds to both hypoxia and inflammatory cytokines, such as TNF-alpha, is useful for assesing the severity of such diseases. Adaptation to hypoxia is regulated primarily by hypoxia inducible transcription factor (HIF alpha) nuclear proteins that engage genes containing a hypoxia response element (HRE). Inflammation activates a multitude of cytokines, including TNF-alpha, that invariably modulate activation of the nuclear factor kappa B (NF-kB) transcription factor. We constructed a vector that encompassed both a hypoxia response element (HRE), and a NF-kappaB responsive element. We show that this vector was functionally responsive to both hypoxia and TNF-alpha, in vitro and in vivo . Thus, this vector might be suitable for the detection and assessment of hypoxia or TNF-alpha.

Induction of oncogene addiction shift to NF-{kappa}B by camptothecin in solid tumor cells

Energy Technology Data Exchange (ETDEWEB)

Togano, Tomiteru; Sasaki, Masataka; Watanabe, Mariko; Nakashima, Makoto [Department of Hematology, School of Medicine, Kitasato University, 1-15-1 Kitasato, Sagamihara, Kanagawa 228-8555 (Japan); Tsuruo, Takashi [Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, 3-10-6 Ariake, Koto-ku, Tokyo 135-8550 (Japan); Umezawa, Kazuo [Department of Applied Chemistry, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama, Kanagawa 223-0061 (Japan); Higashihara, Masaaki [Department of Hematology, School of Medicine, Kitasato University, 1-15-1 Kitasato, Sagamihara, Kanagawa 228-8555 (Japan); Watanabe, Toshiki [Laboratory of Tumor Cell Biology, Department of Medical Genome Sciences, Graduate School of Frontier Sciences, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639 (Japan); Horie, Ryouichi, E-mail: rhorie@med.kitasato-u.ac.jp [Department of Hematology, School of Medicine, Kitasato University, 1-15-1 Kitasato, Sagamihara, Kanagawa 228-8555 (Japan)

2009-12-04

The biological basis of the resistance of solid tumor cells to chemotherapy is not well understood. While addressing this problem, we found that gastric cancer cell line St-4/CPT, lung cancer cell line A549/CPT, and colon cancer cell line HT-29/CPT, all of which are resistant to camptothecin (CPT), showed strong and constitutive nuclear factor (NF)-{kappa}B activity driven by I{kappa}B kinase compared with their parental cell lines St-4, A549, and HT-29. A new NF-{kappa}B inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), reduced viability and induced apoptosis in St-4/CPT, A549/CPT, and HT-29/CPT cell lines, while their parental cell lines were resistant to DHMEQ. The results in this study present an example of the shift in signals that support the survival of solid tumor cells to NF-{kappa}B during the acquisition of resistance to CPT. The results also indicate that solid tumor cells that become resistant to chemotherapy may be more easily treated by NF-{kappa}B inhibitors.

Clonorchis sinensis excretory-secretory products regulate migration and invasion in cholangiocarcinoma cells via extracellular signal-regulated kinase 1/2/nuclear factor-κB-dependent matrix metalloproteinase-9 expression.

Science.gov (United States)

Pak, Jhang Ho; Shin, Jimin; Song, In-Sung; Shim, Sungbo; Jang, Sung-Wuk

2017-01-01

Matrix metalloproteinase-9 plays an important role in the invasion and metastasis of various types of cancer cells. We have previously reported that excretory-secretory products from Clonorchis sinensis increases matrix metalloproteinase-9 expression. However, the regulatory mechanisms through which matrix metalloproteinase-9 expression affects cholangiocarcinoma development remain unclear. In the current study, we examined the potential role of excretory-secretory products in regulating the migration and invasion of various cholangiocarcinoma cell lines. We demonstrated that excretory-secretory products significantly induced matrix metalloproteinase-9 expression and activity in a concentration-dependent manner. Reporter gene and chromatin immunoprecipitation assays showed that excretory-secretory products induced matrix metalloproteinase-9 expression by enhancing the activity of nuclear factor-kappa B. Moreover, excretory-secretory products induced the degradation and phosphorylation of IκBα and stimulated nuclear factor-kappa B p65 nuclear translocation, which was regulated by extracellular signal-regulated kinase 1/2. Taken together, our findings indicated that the excretory-secretory product-dependent enhancement of matrix metalloproteinase-9 activity and subsequent induction of IκBα and nuclear factor-kappa B activities may contribute to the progression of cholangiocarcinoma. Copyright © 2016 Australian Society for Parasitology. Published by Elsevier Ltd. All rights reserved.

Lentiviral-mediated targeted NF-kappaB blockade in dorsal spinal cord glia attenuates sciatic nerve injury-induced neuropathic pain in the rat.

Science.gov (United States)

Meunier, Alice; Latrémolière, Alban; Dominguez, Elisa; Mauborgne, Annie; Philippe, Stéphanie; Hamon, Michel; Mallet, Jacques; Benoliel, Jean-Jacques; Pohl, Michel

2007-04-01

Neuropathic pain developing after peripheral nerve injury is associated with altered neuronal and glial cell functions in the spinal cord. Activated glia produces algogenic mediators, exacerbating pain. Among the different intracellular pathways possibly involved in the modified glial function, the nuclear factor kappaB (NF-kappaB) system is of particular interest, as numerous genes encoding inflammation- and pain-related molecules are controlled by this transcription factor. NF-kappaB is a pleiotropic factor also involved in central nervous system homeostasy. To study its role in chronic pain, it is thus essential to inhibit the NF-kappaB pathway selectively in activated spinal glial cells. Here, we show that when restricted to spinal cord and targeted to glial cells, lentiviral vector-mediated delivery of NF-kappaB super- repressor IkappaBalpha resulted in an inhibition of the NF-kappaB pathway activated in the rat spinal cord after sciatic nerve injury (chronic constriction injury, CCI). Concomitantly, IkappaBalpha overproduction prevented the enhanced expression of interleukin-6 and of inducible nitric oxide synthase associated with chronic constriction injury and resulted in prolonged antihyperalgesic and antiallodynic effects. These data show that targeted blockade of NF-kappaB activity in spinal glia efficiently alleviates pain behavior in CCI rats, demonstrating the active participation of the glial NF-kappaB pathway in the development of neuropathic pain after peripheral nerve injury.

Stimulation of monocytes by placental microparticles involves Toll-like receptors and nuclear factor kappa-light-chain-enhancer of activated B cells

Directory of Open Access Journals (Sweden)

Marianne Simone Joerger-Messerli

2014-04-01

Full Text Available Human pregnancy is accompanied by a mild systemic inflammatory response, which includes the activation of monocytes circulating in maternal blood. This response is exaggerated in preeclampsia, a placental-dependent disorder specific to human pregnancies. We and others showed that placental syncytiotrophoblast membrane microparticles (STBM generated in vitro from normal placentas stimulated peripheral blood monocytes, which suggests a contribution of STBM to the systemic maternal inflammation. Here, we analyzed the inflammatory potential of STBM prepared from preeclamptic placentas on primary monocytes and investigated the mode of action in vitro.STBM generated in vitro by placental villous explants of normal or preeclamptic placentas were co-incubated with human peripheral blood monocytes. In some cases, inhibitors of specific cellular functions or signaling pathways were used. The analysis of the monocytic response was performed by flow cytometry, enzyme-linked immunoassays, real-time PCR and fluorescence microscopy.STBM derived from preeclamptic placentas up-regulated the cell surface expression of CD54, and stimulated the secretion of the pro-inflammatory interleukin (IL-6 and IL-8 in a similar, dose-dependent manner as did STBM prepared from normal placentas. STBM bound to the cell surface of monocytes, but phagocytosis was not necessary for activation. STBM-induced cytokine secretion was impaired in the presence of inhibitors of toll-like receptor (TLR signaling or when nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB activation was blocked.Our results suggest that the inflammatory reaction in monocytes may be initiated by the interaction of STBM with TLRs, which in turn signal through NF-κB to mediate the transcription of genes coding for pro-inflammatory factors.

Enhanced Expression of WD Repeat-Containing Protein 35 via Nuclear Factor-Kappa B Activation in Bupivacaine-Treated Neuro2a Cells

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Huang, Lei; Kondo, Fumio; Harato, Misako; Feng, Guo-Gang; Ishikawa, Naoshisa; Fujiwara, Yoshihiro; Okada, Shoshiro

2014-01-01

The family of WD repeat proteins comprises a large number of proteins and is involved in a wide variety of cellular processes such as signal transduction, cell growth, proliferation, and apoptosis. Bupivacaine is a sodium channel blocker administered for local infiltration, nerve block, epidural, and intrathecal anesthesia. Recently, we reported that bupivacaine induces reactive oxygen species (ROS) generation and p38 mitogen-activated protein kinase (MAPK) activation, resulting in an increase in the expression of WD repeat-containing protein 35 (WDR35) in mouse neuroblastoma Neuro2a cells. It has been shown that ROS activate MAPK through phosphorylation, followed by activation of nuclear factor-kappa B (NF-κB) and activator protein 1 (AP-1). The present study was undertaken to test whether NF-κB and c-Jun/AP-1 are involved in bupivacaine-induced WDR35 expression in Neuro2a cells. Bupivacaine activated both NF-κB and c-Jun in Neuro2a cells. APDC, an NF-κB inhibitor, attenuated the increase in NF-κB activity and WDR35 protein expression in bupivacaine-treated Neuro2a cells. GW9662, a selective peroxisome proliferator-activated receptor-γ antagonist, enhanced the increase in NF-κB activity and WDR35 protein expression in bupivacaine-treated Neuro2a cells. In contrast, c-Jun siRNA did not inhibit the bupivacaine-induced increase in WDR35 mRNA expression. These results indicate that bupivacaine induces the activation of transcription factors NF-κB and c-Jun/AP-1 in Neuro2a cells, while activation of NF-κB is involved in bupivacaine-induced increases in WDR35 expression. PMID:24466034

Omentin inhibits TNF-{alpha}-induced expression of adhesion molecules in endothelial cells via ERK/NF-{kappa}B pathway

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Zhong, Xia, E-mail: zhongxia1977@126.com [Department of Emergency, Provincial Hospital Affiliated to Shandong University, Jinan 250021 (China); Li, Xiaonan; Liu, Fuli; Tan, Hui [Department of Emergency, Provincial Hospital Affiliated to Shandong University, Jinan 250021 (China); Shang, Deya, E-mail: wenhuashenghuo1@163.com [Department of Emergency, Provincial Hospital Affiliated to Shandong University, Jinan 250021 (China)

2012-08-24

Highlights: Black-Right-Pointing-Pointer Omentin inhibited TNF-{alpha}-induced adhesion of THP-1 cells to HUVECs. Black-Right-Pointing-Pointer Omentin reduces expression of ICAM-1 and VCAM-1 induced by TNF-{alpha} in HUVECs. Black-Right-Pointing-Pointer Omentin inhibits TNF-{alpha}-induced ERK and NF-{kappa}B activation in HUVECs. Black-Right-Pointing-Pointer Omentin supreeses TNF-{alpha}-induced expression of ICAM-1 and VCAM-1 via ERK/NF-{kappa}B pathway. -- Abstract: In the present study, we investigated whether omentin affected the expression of intracellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in tumor necrosis factor-{alpha} (TNF-{alpha}) induced human umbilical vein endothelial cells (HUVECs). Our data showed that omentin decreased TNF-{alpha}-induced expression of ICAM-1 and VCAM-1 in HUVECs. In addition, omentin inhibited TNF-{alpha}-induced adhesion of THP-1 cells to HUVECs. Further, we found that omentin inhibited TNF-{alpha}-activated signal pathway of nuclear factor-{kappa}B (NF-{kappa}B) by preventing NF-{kappa}B inhibitory protein (I{kappa}B{alpha}) degradation and NF-{kappa}B/DNA binding activity. Omentin pretreatment significantly inhibited TNF-{alpha}-induced ERK activity and ERK phosphorylation in HUVECs. Pretreatment with PD98059 suppressed TNF-{alpha}-induced NF-{kappa}B activity. Omentin, NF-kB inhibitor (BAY11-7082) and ERK inhibitor (PD98059) reduced the up-regulation of ICAM-1 and VCAM-1 induced by TNF-{alpha}. These results suggest that omentin may inhibit TNF-{alpha}-induced expression of adhesion molecules in endothelial cells via blocking ERK/NF-{kappa}B pathway.

Targeted adenovirus mediated inhibition of NF-kappa B-dependent inflammatory gene expression in endothelial cells in vitro and in vivo

NARCIS (Netherlands)

Kuldo, J. M.; Asgeirsdottir, S. A.; Zwiers, P. J.; Bellu, A. R.; Rots, M. G.; Schalk, J. A. C.; Ogawara, K. I.; Trautwein, C.; Banas, B.; Haisma, H. J.; Molema, G.; Kamps, J. A. A. M.

2013-01-01

In chronic inflammatory diseases the endothelium expresses mediators responsible for harmful leukocyte infiltration. We investigated whether targeted delivery of a therapeutic transgene that inhibits nuclear factor kappa B signal transduction could silence the proinflammatory activation status of

Cirhin up-regulates a canonical NF-{kappa}B element through strong interaction with Cirip/HIVEP1

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Yu, Bin; Mitchell, Grant A. [Genetique Medicale, Centre de Recherche CHU Sainte-Justine, Departement de Pediatrie, Universite de Montreal, Montreal, QC (Canada); Richter, Andrea, E-mail: andrea.richter@umontreal.ca [Genetique Medicale, Centre de Recherche CHU Sainte-Justine, Departement de Pediatrie, Universite de Montreal, Montreal, QC (Canada)

2009-11-01

North American Indian childhood cirrhosis (NAIC/CIRH1A) is a severe autosomal recessive intrahepatic cholestasis. All NAIC patients have a homozygous mutation in CIRH1A that changes conserved Arg565 to Trp (R565W) in Cirhin, a nucleolar protein of unknown function. Subcellular localization is unaffected by the mutation. Yeast two-hybrid screening identified Cirip (Cirhin interaction protein) and found that interaction between Cirip and R565W-Cirhin was weakened. Co-immunoprecipitation of the two proteins from nuclear extracts of HeLa cells strongly supports the yeast two hybrid results. Cirip has essentially the same sequence as the C-terminal of HIVEP1, a regulator of a canonical NF-{kappa}B sequence. Since Cirip has the zinc fingers required for this interaction, we developed an in vitro assay based on this element in mammalian cells to demonstrate functional Cirhin-Cirip interaction. The strong positive effect of Cirip on the NF-{kappa}B sequence was further increased by both Cirhin and R565W-Cirhin. Importantly, the effect of R565W-Cirhin was weaker than that of the wild type protein. We observed increased levels of Cirhin-Cirip complex in nuclear extracts in the presence of this NF-{kappa}B sequence. Our hypothesis is that Cirhin is a transcriptional regulatory factor of this NF-{kappa}B sequence and could be a participant in the regulation of other genes with NF-{kappa}B responsive elements. Since the activities of genes regulated through NF-{kappa}B responsive elements are especially important during development, this interaction may be a key to explain the perinatal appearance of NAIC.

Moringa Oleifera aqueous leaf extract down-regulates nuclear factor-kappaB and increases cytotoxic effect of chemotherapy in pancreatic cancer cells.

Science.gov (United States)

Berkovich, Liron; Earon, Gideon; Ron, Ilan; Rimmon, Adam; Vexler, Akiva; Lev-Ari, Shahar

2013-08-19

Fewer than 6% patients with adenocarcinoma of the pancreas live up to five years after diagnosis. Chemotherapy is currently the standard treatment, however, these tumors often develop drug resistance over time. Agents for increasing the cytotoxic effects of chemotherapy or reducing the cancer cells' chemo-resistance to the drugs are required to improve treatment outcome. Nuclear factor kappa B (NF-kB), a pro-inflammatory transcription factor, reportedly plays a significant role in the resistance of pancreatic cancer cells to apoptosis-based chemotherapy. This study investigated the effect of aqueous Moringa Oleifera leaf extract on cultured human pancreatic cancer cells - Panc-1, p34, and COLO 357, and whether it can potentiates the effect of cisplatin chemotherapy on these cells. The effect of Moringa Oleifera leaf extract alone and in combination with cisplatin on the survival of cultured human pancreatic cancer cells was evaluated by XTT-based colorimetric assay. The distribution of Panc-1 cells in the cell cycle following treatment with Moringa leaf extract was evaluated by flow cytometry, and evaluations of protein levels were via immunoblotting. Data of cell survival following combined treatments were analyzed with Calcusyn software. Moringa Oleifera leaf extract inhibited the growth of all pancreatic cell lines tested. This effect was significant in all cells following exposure to ≥0.75 mg/ml of the extract. Exposure of Panc-1 cells to Moringa leaf extract induced an elevation in the sub-G1 cell population of the cell-cycle, and reduced the expression of p65, p-IkBα and IkBα proteins in crude cell extracts. Lastly, Moringa Oleifera leaf extract synergistically enhanced the cytotoxic effect of cisplatin on Panc-1 cells. Moringa Oleifera leaf extract inhibits the growth of pancreatic cancer cells, the cells NF-κB signaling pathway, and increases the efficacy of chemotherapy in human pancreatic cancer cells.

Hydrogen inhalation reduced epithelial apoptosis in ventilator-induced lung injury via a mechanism involving nuclear factor-kappa B activation

International Nuclear Information System (INIS)

Huang, Chien-Sheng; Kawamura, Tomohiro; Peng, Ximei; Tochigi, Naobumi; Shigemura, Norihisa; Billiar, Timothy R.; Nakao, Atsunori; Toyoda, Yoshiya

2011-01-01

Highlights: → Hydrogen is a regulatory molecule with antiinflammatory and antiapoptotic protective effects. → There is very limited information on the pathways regulated in vivo by the hydrogen. → Antiapoptotic abilities of hydrogen were explained by upregulation of the antiapoptotic gene. → NFκB activation during hydrogen treatment was correlated with elevated antiapoptotic protein. → NFκB activation associated with increase Bcl-2 may contribute to cytoprotection of hydrogen. -- Abstract: We recently demonstrated the inhalation of hydrogen gas, a novel medical therapeutic gas, ameliorates ventilator-induced lung injury (VILI); however, the molecular mechanisms by which hydrogen ameliorates VILI remain unclear. Therefore, we investigated whether inhaled hydrogen gas modulates the nuclear factor-kappa B (NFκB) signaling pathway. VILI was generated in male C57BL6 mice by performing a tracheostomy and placing the mice on a mechanical ventilator (tidal volume of 30 ml/kg or 10 ml/kg without positive end-expiratory pressure). The ventilator delivered either 2% nitrogen or 2% hydrogen in balanced air. NFκB activation, as indicated by NFκB DNA binding, was detected by electrophoretic mobility shift assays and enzyme-linked immunosorbent assay. Hydrogen gas inhalation increased NFκB DNA binding after 1 h of ventilation and decreased NFκB DNA binding after 2 h of ventilation, as compared with controls. The early activation of NFκB during hydrogen treatment was correlated with elevated levels of the antiapoptotic protein Bcl-2 and decreased levels of Bax. Hydrogen inhalation increased oxygen tension, decreased lung edema, and decreased the expression of proinflammatory mediators. Chemical inhibition of early NFκB activation using SN50 reversed these protective effects. NFκB activation and an associated increase in the expression of Bcl-2 may contribute, in part, to the cytoprotective effects of hydrogen against apoptotic and inflammatory signaling pathway

Constitutive activation of alternative nuclear factor kappa B pathway in canine diffuse large B-cell lymphoma contributes to tumor cell survival and is a target of new adjuvant therapies.

Science.gov (United States)

Seelig, Davis M; Ito, Daisuke; Forster, Colleen L; Yoon, Una A; Breen, Matthew; Burns, Linda J; Bachanova, Veronika; Lindblad-Toh, Kerstin; O'Brien, Timothy D; Schmechel, Stephen C; Rizzardi, Anthony E; Modiano, Jaime F; Linden, Michael A

2017-07-01

Activation of the classical nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) pathway is a common molecular event observed in both human and canine diffuse large B-cell lymphoma (DLBCL). Although the oncogenic potential of the alternative NFκB pathway (ANFκBP) has also been recently identified in DLBCL, its precise role in tumor pathogenesis and potential as a treatment target is understudied. We hypothesized that up-regulation of the ANFκBP plays an important role in the proliferation and survival of canine DLBCL cells, and we demonstrate that the ANFκBP is constitutively active in primary canine DLBCL samples and a cell line (CLBL1). We further demonstrate that a small interfering RNA inhibits the activation of the NFκB pathway and induces apoptosis in canine DLBCL cells. In conclusion, the ANFκBP facilitates survival of canine DLBCL cells, and thus, dogs with spontaneous DLBCL can provide a useful large animal model to study therapies targeting the ANFκBP.

Rikkunshito prevents paclitaxel-induced peripheral neuropathy through the suppression of the nuclear factor kappa B (NFκB phosphorylation in spinal cord of mice.

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Junzo Kamei

Full Text Available Peripheral neuropathy is the major side effect caused by paclitaxel, a microtubule-binding antineoplastic drug. Paclitaxel-induced peripheral neuropathy causes a long-term negative impact on the patient's quality of life. However, the mechanism underlying paclitaxel-induced peripheral neuropathy is still unknown, and there is no established treatment. Ghrelin is known to attenuate thermal hyperalgesia and mechanical allodynia in chronic constriction injury of the sciatic nerve, and inhibit the activation of nuclear factor kappa B (NFκB in the spinal dorsal horn. Rikkunshito (RKT, a kampo medicine, increases the secretion of ghrelin in rodents and humans. Thus, RKT may attenuate paclitaxel-induced peripheral neuropathy by inhibiting phosphorylated NFκB (pNFκB in the spinal cord. We found that paclitaxel dose-dependently induced mechanical hyperalgesia in mice. Paclitaxel increased the protein levels of spinal pNFκB, but not those of spinal NFκB. NFκB inhibitor attenuated paclitaxel-induced mechanical hyperalgesia suggesting that the activation of NFκB mediates paclitaxel-induced hyperalgesia. RKT dose-dependently attenuated paclitaxel-induced mechanical hyperalgesia. Ghrelin receptor antagonist reversed the RKT-induced attenuation of paclitaxel-induced mechanical hyperalgesia. RKT inhibited the paclitaxel-induced increase in the protein levels of spinal pNFκB. Taken together, the present study indicates that RKT exerts an antihyperalgesic effect in paclitaxel-induced neuropathic pain by suppressing the activation of spinal NFκB.

Resveratrol enhances radiosensitivity of human non-small cell lung cancer NCI-H838 cells accompanied by inhibition of nuclear factor-kappa B activation

International Nuclear Information System (INIS)

Liao, Hui-Fen; Kuo Cheng-Deng; Yang, Yuh-Cheng; Lin, Chin-Ping; Tai, Hung-Chi; Chen, Yu-Jen; Chen, Yu-Yawn

2005-01-01

Resveratrol, a polyphenol in red wine, possesses many pharmacological activities including cardio-protection, chemoprevention, anti-tumor effects, and nuclear factor-kappa B (NF-κB) inactivation. The present study was designed to evaluate the effects and possible mechanism of resveratrol in enhancing radiosensitivity of lung cancer cells. Human non-small cell lung cancer NCI-H838 cells were irradiated with or without resveratrol pretreatment. The surviving fraction and sensitizer enhancement ratio (SER) were estimated by using a colony formation assay and linear-quadratic model. The cell-cycle distribution was evaluated by using prospidium iodide staining and flow cytometry. An enzyme-linked immunosorbent assay (ELISA)-based assay with immobilized oligonucleotide was performed to assess the DNA binding activity of NF-κB. Resveratrol had no direct growth-inhibitory effect on NCI-H838 cells treated for 24 hours with doses up to 25 μM. Pretreatment with resveratrol significantly enhanced cell killing by radiation, with an SER up to 2.2. Radiation activated NF-κB, an effect reversed by resveratrol pretreatment. Resveratrol resulted in a decrease of cells in the G 0 /G 1 phase and an increase in the S phase. Our results demonstrate that resveratrol enhances the radiosensitivity of NCI-H838 cells accompanied by NF-κB inhibition and S-phase arrest. (author)

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

Energy Technology Data Exchange (ETDEWEB)

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.

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.

Activation of AMP-activated protein kinase by kainic acid mediates brain-derived neurotrophic factor expression through a NF-kappaB dependent mechanism in C6 glioma cells

International Nuclear Information System (INIS)

Yoon, Hana; Oh, Young Taek; Lee, Jung Yeon; Choi, Ji Hyun; Lee, Ju Hie; Baik, Hyung Hwan; Kim, Sung Soo; Choe, Wonchae; Yoon, Kyung-Sik; Ha, Joohun; Kang, Insug

2008-01-01

AMP-activated protein kinase (AMPK) is a key regulator of energy homeostasis. Kainic acid (KA), a prototype excitotoxin is known to induce brain-derived neurotrophic factor (BDNF) in brain. In this study, we examined the role of AMPK in KA-induced BDNF expression in C6 glioma cells. We showed that KA and KA receptor agonist induced activation of AMPK and KA-induced AMPK activation was blocked by inhibition of Ca 2+ /calmodulin-dependent protein kinase kinase (CaMKK) β. We then showed that inhibition of AMPK by compound C, a selective inhibitor of AMPK, or small interfering RNA of AMPKα1 blocked KA-induced BDNF mRNA and protein expression. Inhibition of AMPK blocked KA-induced phosphorylation of CaMKII and I kappaB kinase (IKK) in C6 cells. Finally, we showed that inhibition of AMPK reduced DNA binding and transcriptional activation of nuclear factor-kappaB (NF-κB) in KA-treated cells. These results suggest that AMPK mediates KA-induced BDNF expression by regulating NF-κB activation

Transcriptional down-regulation of thromboxane A(2) receptor expression via activation of MAPK ERK1/2, p38/NF-kappaB pathways

DEFF Research Database (Denmark)

Zhang, Wei; Zhang, Yaping; Edvinsson, Lars

2009-01-01

culture of the arteries, VSMC TP receptors were studied by using myography, real-time PCR and immunohistochemistry. We observed that organ culture for 24 and 48 h resulted in depressed TP receptor-mediated contraction in the VSMC, in parallel with decreased TP receptor mRNA and protein expressions....... Phosphorylation of extracellular signal-regulated kinase 1 and 2 (ERK1/2), p38 and nuclear factor-kappaB (NF-kappaB) was seen by Western blot within 1-3 h after organ culture. Inhibition of ERK1/2, p38 or NF-kappaB reversed depressed contraction as well as decreased receptor mRNA expression. Actinomycin D...

Transcriptional Down-Regulation of Thromboxane A(2) Receptor Expression via Activation of MAPK ERK1/2, p38/NF-kappaB Pathways

DEFF Research Database (Denmark)

Zhang, Wei; Zhang, Yaping; Edvinsson, Lars

2008-01-01

culture of the arteries, VSMC TP receptors were studied by using myography, real-time PCR and immunohistochemistry. We observed that organ culture for 24 and 48 h resulted in depressed TP receptor-mediated contraction in the VSMC, in parallel with decreased TP receptor mRNA and protein expressions....... Phosphorylation of extracellular signal-regulated kinase 1 and 2 (ERK1/2), p38 and nuclear factor-kappaB (NF-kappaB) was seen by Western blot within 1-3 h after organ culture. Inhibition of ERK1/2, p38 or NF-kappaB reversed depressed contraction as well as decreased receptor mRNA expression. Actinomycin D...

NF-{kappa}B p50 promotes tumor cell invasion through negative regulation of invasion suppressor gene CRMP-1 in human lung adenocarcinoma cells

Energy Technology Data Exchange (ETDEWEB)

Ming, Gao [Cancer Research Center, College of Medicine, National Taiwan University, Taipei, Taiwan (China); National Center of Excellence for Clinical Trial and Research, National Taiwan University, Hospital, Taipei, Taiwan (China); Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan (China); Yeh, P Y [Cancer Research Center, College of Medicine, National Taiwan University, Taipei, Taiwan (China); Department of Oncology, National Taiwan University Hospital, No. 7, Chung-Shan South Road, Taipei 10016, Taiwan (China); Lu, Y -S [Cancer Research Center, College of Medicine, National Taiwan University, Taipei, Taiwan (China); National Center of Excellence for Clinical Trial and Research, National Taiwan University, Hospital, Taipei, Taiwan (China); Department of Oncology, National Taiwan University Hospital, No. 7, Chung-Shan South Road, Taipei 10016, Taiwan, ROC (China); Chang, W C [Cancer Research Center, College of Medicine, National Taiwan University, Taipei, Taiwan (China); Kuo, M -L [Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan (China); Cheng, A -L [Cancer Research Center, College of Medicine, National Taiwan University, Taipei, Taiwan (China); National Center of Excellence for Clinical Trial and Research, National Taiwan University, Hospital, Taipei, Taiwan (China); Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan (China); Department of Oncology, National Taiwan University Hospital, No. 7, Chung-Shan South Road, Taipei 10016, Taiwan (China); Department of Internal Medicine, National Taiwan University Hospital, No. 7, Chung-Shan South Road, Taipei 10016, Taiwan (China)], E-mail: alcheng@ntu.edu.tw

2008-11-14

Lung adenocarcinoma Cl1-5 cells were selected from parental Cl1-0 cells based on their high metastatic potential. In a previous study, CRMP-1, an invasion suppressor gene, was shown to be suppressed in Cl1-5 cells. However, the regulation of CRMP-1 expression has not been explored. In this study, we showed nuclear factor-{kappa}B controls CRMP-1 expression. The electromobility shift assay showed that while Cl1-0 cells exhibited low NF-{kappa}B activity in response to TNF-{alpha}, an abundance of basal and TNF-{alpha}-induced NF-{kappa}B-DNA complex was detected in Cl1-5 cells. Supershift-coupled EMSA and Western blotting of nuclear proteins, however, revealed p50 protein, but not classic p65/p50 heterodimer in the complex. ChIP and EMSA demonstrated that p50 binds to a {kappa}B site residing between -1753 and -1743 of the CRMP-1 promoter region. Transfection of antisense p50 gene into Cl1-5 cells increased the CRMP-1 protein level and decreased the invasive activity of Cl1-5 cells.

Flavonoid glycosides from Olax mannii: Structure elucidation and effect on the nuclear factor kappa B pathway.

Science.gov (United States)

Okoye, Festus B C; Sawadogo, Wamtinga Richard; Sendker, Jandirk; Aly, Amal H; Quandt, Bettina; Wray, Victor; Hensel, Andreas; Esimone, Charles O; Debbab, Abdessamad; Diederich, Marc; Proksch, Peter

2015-12-24

Olax mannii Oliv. (Olacaceae) is among the many medicinal plants used in Nigeria for the ethnomedicinal management of both cancer and inflammation. Such plants represent potential sources of innovative therapeutic agents for the treatment of cancer and other malignant disorders. While the majority of medicinal plants exert their anticancer effects by direct cytotoxicity on tumor cells, it is important that other mechanisms through which these plants can exhibit anticancer effects are investigated. Preliminary studies indicated that Olax mannii leaves are rich sources of novel flavonoid glycosides. The detailed chemistry as well the mechanisms through which these flavonoid constituents may exert their cancer chemo-preventive and therapeutic effects are, however, not yet investigated. The aim of this study is to carry out a detailed chemical investigation of Olax mannii leaves and the effects of the isolated constituents on the nuclear factor kappa B (NF-κB) pathway. A methanol leaf extract was subjected to various chromatographic separations to achieve isolation of flavonoid glycosides and the structures of the isolated compounds were elucidated by a combination of 1D and 2D NMR and high resolution mass spectrometry. Biological activities were assessed by measurement of cellular viability and proliferation using quantitative IncuCyte videomicroscopy, trypan blue staining and by quantification of the number of metabolically active K562 cells based on quantitation of ATP. The effect of the compounds on the inhibition of the NF-κB pathway as well as toxicity towards peripheral blood mononuclear cells to evaluate differential toxicity was also assayed. Chemical investigation of the methanol leaf extract of the plant material led to the isolation of three new flavonoid triglycosides, kaempferol 3-O-[α-D-apiofuranosyl-(1 → 2)-α-L-arabinofuranoside]-7-O-α-L-rhamnopyranoside (1), kaempferol 3-O-[β-D-glucopyranosyl-(1 → 2)-α-L-arabinofuranoside]-7-O

p38 mitogen-activated protein kinase up-regulates NF-{kappa}B transcriptional activation through RelA phosphorylation during stretch-induced myogenesis

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Ji, Guoping [Department of Orthodontics, College of Stomatology, Ninth People' s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Research Institute of Stomatology, Shanghai 200011 (China); Liu, Dongxu [Department of Orthodontics, College of Stomatology, Shandong University, Jinan, Shandong Province 250012 (China); Liu, Jing [Department of Orthodontics, The Affiliated Qingdao Municipal Hospital, Qingdao University, Qingdao, Shandong Province 266075 (China); Gao, Hui [Department of Orthodontics, Tianjin Stomatological Hospital, Tianjin 300041 (China); Yuan, Xiao, E-mail: yuanxiaoqd@163.com [Department of Orthodontics, The Affiliated Qingdao Municipal Hospital, Qingdao University, Qingdao, Shandong Province 266075 (China); Shen, Gang, E-mail: ganshen2007@163.com [Department of Orthodontics, College of Stomatology, Ninth People' s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Research Institute of Stomatology, Shanghai 200011 (China)

2010-01-01

p38 MAPK and nuclear factor-B (NF-B) signaling pathways play an indispensable role in the control of skeletal myogenesis. The specific contribution of these signaling pathways to the response of myoblast to the mechanical stimulation and the molecular mechanisms underlying this response remain unresolved. Using an established in vitro model, we now show that p38 MAP kinase activity regulates the transcriptional activation of NF-{kappa}B in response to mechanical stimulation of myoblasts. Furthermore, SB203580 blocked stretch-induced NF-{kappa}B activation during myogenesis, not through down-regulation of degradation of I{kappa}B-{alpha}, and consequent translocation of the p65 subunit of NF-{kappa}B to the nucleus. It is likely that stretch-induced NF-{kappa}B activation by phosphorylation of p65 NF-{kappa}B. Moreover, depletion of p38{alpha} using siRNA significantly reduces stretch-induced phosphorylation of RelA and NF-{kappa}B activity. These results provides the first evidence of a cross-talk between p38 MAPK and NF-{kappa}B signaling pathways during stretch-induced myogenesis, with phosphorylation of RelA being one of the effectors of this promyogenic mechanism. The {alpha} isoform of p38MAP kinase regulates the transcriptional activation of NF-{kappa}B following stimulation with cyclic stretch.

A Smac-mimetic sensitizes prostate cancer cells to TRAIL-induced apoptosis via modulating both IAPs and NF-kappaB

International Nuclear Information System (INIS)

Dai, Yao; Liu, Meilan; Tang, Wenhua; Li, Yongming; Lian, Jiqin; Lawrence, Theodore S; Xu, Liang

2009-01-01

Although tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising agent for human cancer therapy, prostate cancer still remains resistant to TRAIL. Both X-linked inhibitor of apoptosis (XIAP) and nuclear factor-kappaB function as key negative regulators of TRAIL signaling. In this study, we evaluated the effect of SH122, a small molecule mimetic of the second mitochondria-derived activator of caspases (Smac), on TRAIL-induced apoptosis in prostate cancer cells. The potential of Smac-mimetics to bind XIAP or cIAP-1 was examined by pull-down assay. Cytotoxicity of TRAIL and/or Smac-mimetics was determined by a standard cell growth assay. Silencing of XIAP or cIAP-1 was achieved by transient transfection of short hairpin RNA. Apoptosis was detected by Annexin V-PI staining followed by flow cytometry and by Western Blot analysis of caspases, PARP and Bid. NF-kappaB activation was determined by subcellular fractionation, real time RT-PCR and reporter assay. SH122, but not its inactive analog, binds to XIAP and cIAP-1. SH122 significantly sensitized prostate cancer cells to TRAIL-mediated cell death. Moreover, SH122 enhanced TRAIL-induced apoptosis via both the death receptor and the mitochondrial pathway. Knockdown of both XIAP and cIAP-1 sensitized cellular response to TRAIL. XIAP-knockdown attenuated sensitivity of SH122 to TRAIL-induced cytotoxicity, confirming that XIAP is an important target for IAP-inhibitor-mediated TRAIL sensitization. SH122 also suppressed TRAIL-induced NF-kappaB activation by preventing cytosolic IkappaB-alpha degradation and RelA nuclear translocation, as well as by suppressing NF-kappaB target gene expression. These results demonstrate that SH122 sensitizes human prostate cancer cells to TRAIL-induced apoptosis by mimicking Smac and blocking both IAPs and NF-kappaB. Modulating IAPs may represent a promising approach to overcoming TRAIL-resistance in human prostate cancer with constitutively active NF-kappaB signaling

Ebselen Is a Potential Anti-Osteoporosis Agent by Suppressing Receptor Activator of Nuclear Factor Kappa-B Ligand-Induced Osteoclast Differentiation In vitro and Lipopolysaccharide-Induced Inflammatory Bone Destruction In vivo.

Science.gov (United States)

Baek, Jong Min; Kim, Ju-Young; Yoon, Kwon-Ha; Oh, Jaemin; Lee, Myeung Su

2016-01-01

Ebselen is a non-toxic seleno-organic drug with anti-inflammatory and antioxidant properties that is currently being examined in clinical trials to prevent and treat various diseases, including atherosclerosis, stroke, and cancer. However, no reports are available for verifying the pharmacological effects of ebselen on major metabolic bone diseases such as osteoporosis. In this study, we observed that ebselen suppressed the formation of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells in an osteoblast/osteoclast co-culture by regulating the ratio of receptor activator of nuclear factor kappa-B ligand (RANKL)/osteoprotegerin secreted by osteoblasts. In addition, ebselen treatment in the early stage of osteoclast differentiation inhibited RANKL-dependent osteoclastogenesis by decreasing the phosphorylation of IκB, PI3K, and Akt in early signaling pathways and by subsequently inducing c-Fos and nuclear factor of activated T-cells c1. Further, ebselen induced apoptosis of osteoclasts in the late stage of osteoclast differentiation. In addition, ebselen treatment suppressed filamentous actin ring formation and bone resorption activity of mature osteoclasts. Reflecting these in vitro effects, administration of ebselen recovered bone loss and its µ-CT parameters in lipopolysaccharide-mediated mouse model. Histological analysis confirmed that ebselen prevented trabecular bone matrix degradation and osteoclast formation in the bone tissues. Finally, it was proved that the anti-osteoclastogenic action of ebselen is achieved through targeting N-methyl-D-aspartate (NMDA) receptor. These results indicate that ebselen is a potentially safe drug for treating metabolic bone diseases such as osteoporosis.

Stimulation of interleukin-13 expression by human T-cell leukemia virus type 1 oncoprotein Tax via a dually active promoter element responsive to NF-kappaB and NFAT.

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Silbermann, Katrin; Schneider, Grit; Grassmann, Ralph

2008-11-01

The human T-cell leukemia virus type 1 (HTLV-1) Tax oncoprotein transforms human lymphocytes and is critical for the pathogenesis of HTLV-1-induced adult T-cell leukaemia. In HTLV-transformed cells, Tax upregulates interleukin (IL)-13, a cytokine with proliferative and anti-apoptotic functions that is linked to leukaemogenesis. Tax-stimulated IL-13 is thought to result in autocrine stimulation of HTLV-infected cells and thus may be relevant to their growth. The causal transactivation of the IL-13 promoter by Tax is predominantly dependent on a nuclear factor of activated T cells (NFAT)-binding P element. Here, it was shown that the isolated IL-13 Tax-responsive element (IL13TaxRE) was sufficient to mediate IL-13 transactivation by Tax and NFAT1. However, cyclosporin A, a specific NFAT inhibitor, revealed that Tax transactivation of IL13TaxRE or wild-type IL-13 promoter was independent of NFAT and that NFAT did not contribute to IL-13 upregulation in HTLV-transformed cells. By contrast, Tax stimulation was repressible by an efficient nuclear factor (NF)-kappaB inhibitor (IkBaDN), indicating the requirement for NF-kappaB. The capacity of NF-kappaB to stimulate IL13TaxRE was demonstrated by a strong response to NF-kappaB in reporter assays and by direct binding of NF-kappaB to IL13TaxRE. Thus, IL13TaxRE in the IL-13 promoter represents a dually active promoter element responsive to NF-kappaB and NFAT. Together, these results indicate that Tax causes IL-13 upregulation in HTLV-1-infected cells via NF-kappaB.

New treatment of periodontal diseases by using NF-kappaB decoy oligodeoxynucleotides via prevention of bone resorption and promotion of wound healing.

Science.gov (United States)

Shimizu, Hideo; Nakagami, Hironori; Morita, Shosuke; Tsukamoto, Ikuyo; Osako, Mariana Kiomy; Nakagami, Futoshi; Shimosato, Takashi; Minobe, Noriko; Morishita, Ryuichi

2009-09-01

Nuclear factor-kappa B (NF-kappaB) is involved in osteoclast differentiation and activation. Thus, the blockade of the NF-kappaB pathway might be a novel therapeutic strategy for treating bone metabolic diseases. Periodontitis is subgingival inflammation caused by bacterial infection; this disease also is thought to be a chronic focal point responsible for systemic diseases. In this study, NF-kappaB decoy oligodeoxynucleotides (ODNs) were topically applied for experimental periodontitis in a debris-accumulation model and wound healing in a bone-defect model of beagle dogs to investigate the effect of decoy ODN on bone metabolism. Application of NF-kappaB decoy ODN significantly reduced interleukin-6 activity in crevicular fluid and improved alveolar bone loss in the analysis of dental radiographs and DEXA. Direct measurement of exposed root that lost alveolar bone support revealed that NF-kappaB decoy treatment dramatically protected bone from loss. In a bone-defect model, NF-kappaB decoy ODN promoted the healing process as compared with control scrambled decoy in micro-CT analysis. Overall, inhibition of NF-kappaB by decoy strategy prevented the progression of bone loss in periodontitis and promoted the wound healing in bone defects through the inhibition of osteoclastic bone resorption. Targeting of NF-kappaB might be a potential therapy in various bone metabolic diseases.

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...

The relation between the photonuclear E1 sum rule and the effective orbital g-factor

Energy Technology Data Exchange (ETDEWEB)

Bentz, Wolfgang E-mail: bentz@keyaki.cc.u-tokai.ac.jp; Arima, Akito

2004-05-17

The connection between the enhancement factor (1+{kappa}) of the photonuclear E1 sum rule and the orbital angular momentum g-factor (g{sub l}) of a bound nucleon is investigated in the framework of the Landau-Migdal theory for isospin asymmetric nuclear matter. Special emphasis is put on the role of gauge invariance to establish the {kappa}-g{sub l} relation. By identifying the physical processes which are taken into account in {kappa} and g{sub l}, the validity and limitations of this relation will be discussed. The connections to the collective excitations and to nuclear Compton scattering are also shown.

Dexamethasone protects RAW264.7 macrophages from growth arrest and apoptosis induced by H2O2 through alteration of gene expression patterns and inhibition of nuclear factor-kappa B (NF-κB) activity

International Nuclear Information System (INIS)

Fong, C.-C.; Zhang Yaou; Zhang Qi; Tzang, C.-H.; Fong, W.-F.; Wu, R.S.S.; Yang Mengsu

2007-01-01

In this study, the effect of dexamethasone, a synthetic glucocorticoid, on H 2 O 2 stimulated murine RAW264.7 macrophages was investigated. It was found that dexamethasone protected the cells from apoptosis induced by H 2 O 2 . A cDNA microarray, which consists of 1000 genes selected from a mouse clone set provided from NIA, was used to study the gene expression profiles involved in the protective effect. Our data show that dexamethasone exerts the anti-apoptosis function by changing the expression patterns of many genes involved inhibiting the up-regulation of apoptosis promoting genes and the down-regulation of cell cycle stimulating genes as well as keeping the up-regulation of cell survival related genes. Our study also revealed that dexamethasone protects RAW264.7 macrophages from H 2 O 2 induced apoptosis through blocking nuclear factor-kappa B (NF-κB) activity

Interleukin (IL) 36 gamma induces mucin 5AC, oligomeric mucus/gel-forming expression via IL-36 receptor-extracellular signal regulated kinase 1 and 2, and p38-nuclear factor kappa-light-chain-enhancer of activated B cells in human airway epithelial cells.

Science.gov (United States)

Bae, Chang Hoon; Choi, Yoon Seok; Na, Hyung Gyun; Song, Si-Youn; Kim, Yong-Dae

2018-03-01

Mucin 5AC, oligomeric mucus/gel-forming (MUC5AC) expression is significantly increased in allergic and inflammatory airway diseases. Interleukin (IL) 36 gamma is predominantly expressed in airway epithelial cells and plays an important role in innate and adaptive immune responses. IL-36 gamma is induced by many inflammatory mediators, including cytokines and bacterial and viral infections. However, the association between IL-36 gamma and mucin secretion in human airway epithelial cells has not yet been fully investigated. The objective of this study was to determine whether IL-36 gamma might play a role in the regulation of mucin secretion in airway epithelial cells. We investigated the effect and brief signaling pathway of IL-36 gamma on MUC5AC expression in human airway epithelial cells. Enzyme immunoassay, immunoblot analysis, immunofluorescence staining, reverse transcriptase-polymerase chain reaction (PCR), and real-time PCR were performed in mucin-producing human airway epithelial NCI-H292 cells and in human nasal epithelial cells after pretreatment with IL-36 gamma, several specific inhibitors, or small interfering RNAs (siRNA). IL-36 gamma induced MUC5AC expression and activated the phosphorylation of extracellular signal regulated kinase (ERK) 1 and 2, p38, and nuclear factor-kappa-light-chain-enhancer of activated B cells (NF-kappa B). IL-36 receptor antagonist significantly attenuated these effects. The specific inhibitor and siRNA of ERK1, ERK2, p38, and NF-kappa B significantly attenuated IL-36 gamma induced MUC5AC expression. These results indicated that IL-36 gamma induced MUC5AC expression via the IL-36 receptor-mediated ERK1/2 and p38/NF-kappa B pathway in human airway epithelial cells.

NF-kappaB specifically activates BMP-2 gene expression in growth plate chondrocytes in vivo and in a chondrocyte cell line in vitro.

Science.gov (United States)

Feng, Jian Q; Xing, Lianping; Zhang, Jiang-Hong; Zhao, Ming; Horn, Diane; Chan, Jeannie; Boyce, Brendan F; Harris, Stephen E; Mundy, Gregory R; Chen, Di

2003-08-01

Bone morphogenetic protein-2 (BMP-2) regulates growth plate chondrogenesis during development and postnatal bone growth, but the control mechanisms of BMP-2 expression in growth plate chondrocytes are unknown. Here we have used both in vitro and in vivo approaches to demonstrate that transcription factor, NF-kappaB, regulates BMP-2 gene expression in chondrocytes. Two putative NF-kappaB response elements were found in the -2712/+165 region of the BMP-2 gene. Cotransfection of mutant I-kappaBalpha expression plasmids with BMP-2 promoter-luciferase reporters into TMC-23 chondrocyte cell line suppressed BMP-2 transcription. Mutations in NF-kappaB response elements in the BMP-2 gene lead to decreases in BMP-2 promoter activity. Electrophoretic mobility shift assay using nuclear extracts from TMC-23 chondrocytic cells revealed that the NF-kappaB subunits p50 and p65 bound to the NF-kappaB response elements of the BMP-2 gene. Thus, NF-kappaB may positively regulate BMP-2 gene transcription. Consistent with these findings, expression of BMP-2 mRNA was significantly reduced in growth plate chondrocytes in NF-kappaB p50/p52 dKO mice, which associated with decreased numbers of 5-bromo-2'-deoxyuridine (BrdUrd)-positive cells in the proliferating zone of growth plate in these mice. Therefore, in postnatal growth plate chondrocytes, expression of BMP-2 is regulated by NF-kappaB, which may play an important role in chondrogenesis.

1,25-dihydroxyvitamin D{sub 3} impairs NF-{kappa}B activation in human naive B cells

Energy Technology Data Exchange (ETDEWEB)

Geldmeyer-Hilt, Kerstin, E-mail: kerstin.hilt@charite.de [Allergie-Centrum-Charite, CCM, Klinik fuer Dermatologie und Allergologie, Charite - Universitaetsmedizin Berlin, Chariteplatz 1, 10117 Berlin (Germany); Heine, Guido, E-mail: guido.heine@charite.de [Allergie-Centrum-Charite, CCM, Klinik fuer Dermatologie und Allergologie, Charite - Universitaetsmedizin Berlin, Chariteplatz 1, 10117 Berlin (Germany); Deutsches Rheuma-Forschungszentrum Berlin, Chariteplatz 1, 10117 Berlin (Germany); Hartmann, Bjoern, E-mail: bjoern.hartmann@charite.de [Allergie-Centrum-Charite, CCM, Klinik fuer Dermatologie und Allergologie, Charite - Universitaetsmedizin Berlin, Chariteplatz 1, 10117 Berlin (Germany); Baumgrass, Ria, E-mail: baumgrass@drfz.de [Deutsches Rheuma-Forschungszentrum Berlin, Chariteplatz 1, 10117 Berlin (Germany); Radbruch, Andreas, E-mail: radbruch@drfz.de [Deutsches Rheuma-Forschungszentrum Berlin, Chariteplatz 1, 10117 Berlin (Germany); Worm, Margitta, E-mail: margitta.worm@charite.de [Allergie-Centrum-Charite, CCM, Klinik fuer Dermatologie und Allergologie, Charite - Universitaetsmedizin Berlin, Chariteplatz 1, 10117 Berlin (Germany)

2011-04-22

Highlights: {yields} In naive B cells, VDR activation by calcitriol results in reduced NF-{kappa}B p105 and p50 protein expression. {yields} Ligating the VDR with calcitriol causes reduced nuclear translocation of NF-{kappa}B p65. {yields} Reduced nuclear amount of p65 after calcitriol incubation results in reduced binding of p65 on the p105 promoter. {yields} Thus, vitamin D receptor signaling may reduce or prevent activation of B cells and unwanted immune responses, e.g. in IgE dependent diseases such as allergic asthma. -- Abstract: 1{alpha},25-dihydroxyvitamin D{sub 3} (calcitriol), the bioactive metabolite of vitamin D, modulates the activation and inhibits IgE production of anti-CD40 and IL-4 stimulated human peripheral B cells. Engagement of CD40 results in NF-{kappa}B p50 activation, which is essential for the class switch to IgE. Herein, we investigated by which mechanism calcitriol modulates NF-{kappa}B mediated activation of human naive B cells. Naive B cells were predominantly targeted by calcitriol in comparison with memory B cells as shown by pronounced induction of the VDR target gene cyp24a1. Vitamin D receptor activation resulted in a strongly reduced p105/p50 protein and mRNA expression in human naive B cells. This effect is mediated by impaired nuclear translocation of p65 and consequently reduced binding of p65 to its binding site in the p105 promoter. Our data indicate that the vitamin D receptor reduces NF-{kappa}B activation by interference with NF-{kappa}B p65 and p105. Thus, the vitamin D receptor inhibits costimulatory signal transduction in naive B cells, namely by reducing CD40 signaling.

Long-term intravenous administration of carboxylated single-walled carbon nanotubes induces persistent accumulation in the lungs and pulmonary fibrosis via the nuclear factor-kappa B pathway

Directory of Open Access Journals (Sweden)

Qin Y

2016-12-01

Full Text Available Yue Qin,1,* Suning Li,2,* Gan Zhao,2,* Xuanhao Fu,1 Xueping Xie,1 Yiyi Huang,1 Xiaojing Cheng,3 Jinbin Wei,1 Huagang Liu,1 Zefeng Lai1 1Pharmaceutical College, Guangxi Medical University, 2Department of Pharmacy, The Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, 3Life Sciences Institute, Guangxi Medical University, Nanning, Guangxi, People’s Republic of China *These authors contributed equally to this work Abstract: Numerous studies have demonstrated promising application of single-walled carbon nanotubes (SWNTs in drug delivery, diagnosis, and targeted therapy. However, the adverse health effects resulting from intravenous injection of SWNTs are not completely understood. Studies have shown that levels of “pristine” or carboxylated carbon nanotubes are very high in mouse lungs after intravenous injection. We hypothesized that long-term and repeated intravenous administration of carboxylated SWNTs (c-SWNTs can result in persistent accumulation and induce histopathologic changes in rat lungs. Here, c-SWNTs were administered repeatedly to rats via tail-vein injection for 90 days. Long-term intravenous injection of c-SWNTs caused sustained embolization in lung capillaries and granuloma formation. It also induced a persistent inflammatory response that was regulated by the nuclear factor-kappa B signaling pathway, and which resulted in pulmonary fibrogenesis. c-SWNTs trapped within lung capillaries traversed capillary walls and injured alveolar epithelial cells, thereby stimulating production of pro-inflammatory cytokines (tumor necrosis factor-alpha and interleukin-1 beta and pro-fibrotic growth factors (transforming growth factor-beta 1. Protein levels of type-I and type-III collagens, matrix metalloproteinase-2, and the tissue inhibitor of metalloproteinase-2 were upregulated after intravenous exposure to c-SWNTs as determined by immunohistochemical assays and Western blotting, which suggested collagen deposition

Theobromine, the primary methylxanthine found in Theobroma cacao, prevents malignant glioblastoma proliferation by negatively regulating phosphodiesterase-4, extracellular signal-regulated kinase, Akt/mammalian target of rapamycin kinase, and nuclear factor-kappa B.

Science.gov (United States)

Sugimoto, Naotoshi; Miwa, Shinji; Hitomi, Yoshiaki; Nakamura, Hiroyuki; Tsuchiya, Hiroyuki; Yachie, Akihiro

2014-01-01

Theobromine, a caffeine derivative, is the primary methylxanthine produced by Theobroma cacao. We previously showed that methylxanthines, including caffeine and theophylline, have antitumor and antiinflammatory effects, which are in part mediated by their inhibition of phosphodiesterase (PDE). A member of the PDE family, PDE4, is widely expressed in and promotes the growth of glioblastoma, the most common type of brain tumor. The purpose of this study was to determine whether theobromine could exert growth inhibitory effects on U87-MG, a cell line derived from human malignant glioma. We show that theobromine treatment elevates intracellular cAMP levels and increases the activity of p38 mitogen-activated protein kinase and c-Jun N-terminal kinase, whereas it attenuates p44/42 extracellular signal-regulated kinase activity and the Akt/mammalian target of rapamycin kinase and nuclear factor-kappa B signal pathways. It also inhibits cell proliferation. These results suggest that foods and beverages containing cocoa bean extracts, including theobromine, might be extremely effective in preventing human glioblastoma.

Nuclear factor kappa B: a pro-inflammatory, transcription factor-mediated signalling pathway in lung carcinogenesis and its inhibition by nonsteroidal anti-inflammatory drugs.

Science.gov (United States)

Setia, Shruti; Sanyal, Sankar Nath

2012-01-01

9,10-Dimethyl benz(a)anthracene (DMBA), when injected intratracheally once at a dose of 20 mg/kg body weight, is found to induce lung cancer in rats. Two nonsteroidal anti-inflammatory drugs (NSAIDs), indomethacin and etoricoxib, are given orally daily as chemopreventive agents at a dose of 0.6 mg/kg body weight and 2 mg/kg body weight, respectively, along with DMBA. Morphologic and histologic analysis revealed the occurence of tumors and intense cellular proliferation in the DMBA-treated animals, whereas no such features were observed in the other groups. Nuclear factor κB, a nuclear transcription factor, and proliferating cell nuclear antigen, a cell proliferation antigen, were studied by immunoblotting and immunohistochemistry and their levels were markedly elevated in the DMBA group compared with the others. Oxidative stress parameters, as studied by the inducible nitric oxide synthase activity, and the levels of reactive oxygen and nitrogen species were found to be suppressed in the DMBA group. Furthermore, fluorescent staining of the isolated lung cells from bronchoalveolar lavage was performed to study apoptosis and alterations in the mitochondrial membrane potential, and the DMBA-induced lung cancer was found to be associated with high inner mitochondrial membrane potential and a suppressed level of apoptosis.

20-Hydroxycholecalciferol, product of vitamin D3 hydroxylation by P450scc, decreases NF-kappaB activity by increasing IkappaB alpha levels in human keratinocytes.

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Zorica Janjetovic

Full Text Available The side chain of vitamin D3 is hydroxylated in a sequential manner by cytochrome P450scc (CYP11A1 to form 20-hydroxycholecalciferol, which can induce growth arrest and differentiation of both primary and immortalized epidermal keratinocytes. Since nuclear factor-kappaB (NF-kappaB plays a pivotal role in the regulation of cell proliferation, differentiation and apoptosis, we examined the capability of 20-hydroxycholecalciferol to modulate the activity of NF-kappaB, using 1,25-dihydroxycholecalciferol (calcitriol as a positive control. 20-hydroxycholecalciferol inhibits the activation of NFkappaB DNA binding activity as well as NF-kappaB-driven reporter gene activity in keratinocytes. Also, 20-hydroxycholecalciferol induced significant increases in the mRNA and protein levels of the NF-kappaB inhibitor protein, IkappaB alpha, in a time dependent manner, while no changes in total NF-kappaB-p65 mRNA or protein levels were observed. Another measure of NF-kappaB activity, p65 translocation from the cytoplasm into the nucleus was also inhibited in extracts of 20-hydroxycholecalciferol treated keratinocytes. Increased IkappaB alpha was concomitantly observed in cytosolic extracts of 20-hydroxycholecalciferol treated keratinocytes, as determined by immunoblotting and immunofluorescent staining. In keratinocytes lacking vitamin D receptor (VDR, 20-hydroxycholecalciferol did not affect IkappaB alpha mRNA levels, indicating that it requires VDR for its action on NF-kappaB activity. Comparison of the effects of calcitrol, hormonally active form of vitamin D3, with 20-hydrocholecalciferol show that both agents have a similar potency in inhibiting NF-kappaB. Since NF-kappaB is a major transcription factor for the induction of inflammatory mediators, our findings indicate that 20-hydroxycholecalciferol may be an effective therapeutic agent for inflammatory and hyperproliferative skin diseases.

NF-kappaB: Two Sides of the Same Coin.

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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.

Metastatic function of BMP-2 in gastric cancer cells: The role of PI3K/AKT, MAPK, the NF-{kappa}B pathway, and MMP-9 expression

Energy Technology Data Exchange (ETDEWEB)

Kang, Myoung Hee [Graduate School of Medicine, Korea University College of Medicine, Korea University, Seoul 136-705 (Korea, Republic of); Oh, Sang Cheul [Division of Oncology/Hematology, Department of Internal Medicine, Korea University College of Medicine, Korea University, Seoul 136-705 (Korea, Republic of); Lee, Hyun Joo [Department of Pathology, Korea University College of Medicine, Korea University, Seoul 136-705 (Korea, Republic of); Kang, Han Na; Kim, Jung Lim [Graduate School of Medicine, Korea University College of Medicine, Korea University, Seoul 136-705 (Korea, Republic of); Kim, Jun Suk [Division of Oncology/Hematology, Department of Internal Medicine, Korea University College of Medicine, Korea University, Seoul 136-705 (Korea, Republic of); Yoo, Young A., E-mail: ydanbi@korea.ac.kr [Brain Korea 21 Program for Biomedical Science, Korea University College of Medicine, Korea University, Seoul 136-705 (Korea, Republic of)

2011-07-15

Bone morphogenetic proteins (BMPs) have been implicated in tumorigenesis and metastatic progression in various types of cancer cells, but the role and cellular mechanism in the invasive phenotype of gastric cancer cells is not known. Herein, we determined the roles of phosphoinositide 3-kinase (PI3K)/AKT, extracellular signal-regulated protein kinase (ERK), nuclear factor (NF)-{kappa}B, and matrix metalloproteinase (MMP) expression in BMP-2-mediated metastatic function in gastric cancer. We found that stimulation of BMP-2 in gastric cancer cells enhanced the phosphorylation of AKT and ERK. Accompanying activation of AKT and ERK kinase, BMP-2 also enhanced phosphorylation/degradation of I{kappa}B{alpha} and the nuclear translocation/activation of NF-{kappa}B. Interestingly, blockade of PI3K/AKT and ERK signaling using LY294002 and PD98059, respectively, significantly inhibited BMP-2-induced motility and invasiveness in association with the activation of NF-{kappa}B. Furthermore, BMP-2-induced MMP-9 expression and enzymatic activity was also significantly blocked by treatment with PI3K/AKT, ERK, or NF-{kappa}B inhibitors. Immunohistochemistry staining of 178 gastric tumor biopsies indicated that expression of BMP-2 and MMP-9 had a significant positive correlation with lymph node metastasis and a poor prognosis. These results indicate that the BMP-2 signaling pathway enhances tumor metastasis in gastric cancer by sequential activation of the PI3K/AKT or MAPK pathway followed by the induction of NF-{kappa}B and MMP-9 activity, indicating that BMP-2 has the potential to be a therapeutic molecular target to decrease metastasis.

Upregulation of cystathionine beta-synthetase expression by nuclear factor-kappa B activation contributes to visceral hypersensitivity in adult rats with neonatal maternal deprivation

Directory of Open Access Journals (Sweden)

Li Lin

2012-12-01

Full Text Available Abstract Background Irritable bowel syndrome (IBS is characterized by chronic visceral hyperalgesia (CVH that manifested with persistent or recurrent abdominal pain and altered bowel movement. However, the pathogenesis of the CVH remains unknown. The aim of this study was to investigate roles of endogenous hydrogen sulfide (H2S producing enzyme cystathionine beta-synthetase (CBS and p65 nuclear factor-kappa B subunits in CVH. Results CVH was induced by neonatal maternal deprivation (NMD in male rats on postnatal days 2–15 and behavioral experiments were conducted at the age of 7–15 weeks. NMD significantly increased expression of CBS in colon-innervating DRGs from the 7th to 12th week. This change in CBS express is well correlated with the time course of enhanced visceromoter responses to colorectal distention (CRD, an indicator of visceral pain. Administration of AOAA, an inhibitor of CBS, produced a dose-dependent antinociceptive effect on NMD rats while it had no effect on age-matched healthy control rats. AOAA also reversed the enhanced neuronal excitability seen in colon-innervating DRGs. Application of NaHS, a donor of H2S, increased excitability of colon-innervating DRG neurons acutely dissociated from healthy control rats. Intrathecal injection of NaHS produced an acute visceral hyperalgesia. In addition, the content of p65 in nucleus was remarkably higher in NMD rats than that in age-matched controls. Intrathecal administration of PDTC, an inhibitor of p65, markedly reduced expression of CBS and attenuated nociceptive responses to CRD. Conclusion The present results suggested that upregulation of CBS expression, which is mediated by activation of p65, contributes to NMD-induced CVH. This pathway might be a potential target for relieving CVH in patients with IBS.

Esculetin attenuates receptor activator of nuclear factor kappa-B ligand-mediated osteoclast differentiation through c-Fos/nuclear factor of activated T-cells c1 signaling pathway

Energy Technology Data Exchange (ETDEWEB)

Baek, Jong Min; Park, Sun-Hyang; Cheon, Yoon-Hee; Ahn, Sung-Jun [Department of Anatomy, School of Medicine, Wonkwang University, Iksan, Jeonbuk 570-749 (Korea, Republic of); Lee, Myeung Su [Division of Rheumatology, Department of Internal Medicine, Wonkwang University, Iksan, Jeonbuk 570-749 (Korea, Republic of); Imaging Science-based Lung and Bone Diseases Research Center, Wonkwang University, Iksan, Jeonbuk 570-749 (Korea, Republic of); Institute for Skeletal Disease, Wonkwang University, Iksan, Jeonbuk 570-749 (Korea, Republic of); Oh, Jaemin, E-mail: jmoh@wku.ac.kr [Department of Anatomy, School of Medicine, Wonkwang University, Iksan, Jeonbuk 570-749 (Korea, Republic of); Imaging Science-based Lung and Bone Diseases Research Center, Wonkwang University, Iksan, Jeonbuk 570-749 (Korea, Republic of); Institute for Skeletal Disease, Wonkwang University, Iksan, Jeonbuk 570-749 (Korea, Republic of); Kim, Ju-Young, E-mail: kimjy1014@gmail.com [Imaging Science-based Lung and Bone Diseases Research Center, Wonkwang University, Iksan, Jeonbuk 570-749 (Korea, Republic of)

2015-05-29

Esculetin exerts various biological effects on anti-oxidation, anti-tumors, and anti-inflammation. However, the involvement of esculetin in the bone metabolism process, particularly osteoclast differentiation has not yet been investigated. In the present study, we first confirmed the inhibitory effect of esculetin on receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast formation. We then revealed the relationship between esculetin and the expression of osteoclast-specific molecules to elucidate its underlying mechanisms. Esculetin interfered with the expression of c-Fos and nuclear factor of activated T cell c1 (NFATc1) both at the mRNA and protein level with no involvement in osteoclast-associated early signaling pathways, suppressing the expression of various transcription factors exclusively expressed in osteoclasts such as tartrate-resistant acid phosphatase (Trap), osteoclast-associated receptor (Oscar), dendritic cell-specific transmembrane protein (Dcstamp), osteoclast stimulatory transmembrane protein (Ocstamp), cathepsin K, αvβ3 integrin, and calcitonin receptor (Ctr). Additionally, esculetin inhibited the formation of filamentous actin (F-actin) ring-positive osteoclasts during osteoclast differentiation. However, the development of F-actin structures and subsequent bone resorbing activity of mature osteoclasts, which are observed in osteoclast/osteoblast co-culture systems were not affected by esculetin. Taken together, our results indicate for the first time that esculetin inhibits RANKL-mediated osteoclastogenesis via direct suppression of c-Fos and NFATc1 expression and exerts an inhibitory effect on actin ring formation during osteoclastogenesis. - Highlights: • We first investigated the effects of esculetin on osteoclast differentiation and function. • Our data demonstrate for the first time that esculetin can suppress osteoclastogenesis in vitro. • Esculetin acts as an inhibitor of c-Fos and NFATc1 activation. �

Synergistic chondroprotective effects of curcumin and resveratrol in human articular chondrocytes: inhibition of IL-1beta-induced NF-kappaB-mediated inflammation and apoptosis.

Science.gov (United States)

Csaki, Constanze; Mobasheri, Ali; Shakibaei, Mehdi

2009-01-01

Currently available treatments for osteoarthritis (OA) are restricted to nonsteroidal anti-inflammatory drugs, which exhibit numerous side effects and are only temporarily effective. Thus novel, safe and more efficacious anti-inflammatory agents are needed for OA. Naturally occurring polyphenolic compounds, such as curcumin and resveratrol, are potent agents for modulating inflammation. Both compounds mediate their effects by targeting the NF-kappaB signalling pathway. We have recently demonstrated that in chondrocytes resveratrol modulates the NF-kappaB pathway by inhibiting the proteasome, while curcumin modulates the activation of NF-kappaB by inhibiting upstream kinases (Akt). However, the combinational effects of these compounds in chondrocytes has not been studied and/or compared with their individual effects. The aim of this study was to investigate the potential synergistic effects of curcumin and resveratrol on IL-1beta-stimulated human chondrocytes in vitro using immunoblotting and electron microscopy. Treatment with curcumin and resveratrol suppressed NF-kappaB-regulated gene products involved in inflammation (cyclooxygenase-2, matrix metalloproteinase (MMP)-3, MMP-9, vascular endothelial growth factor), inhibited apoptosis (Bcl-2, Bcl-xL, and TNF-alpha receptor-associated factor 1) and prevented activation of caspase-3. IL-1beta-induced NF-kappaB activation was suppressed directly by cocktails of curcumin and resveratrol through inhibition of Ikappakappa and proteasome activation, inhibition of IkappaBalpha phosphorylation and degradation, and inhibition of nuclear translocation of NF-kappaB. The modulatory effects of curcumin and resveratrol on IL-1beta-induced expression of cartilage specific matrix and proinflammatory enzymes were mediated in part by the cartilage-specific transcription factor Sox-9. We propose that combining these natural compounds may be a useful strategy in OA therapy as compared with separate treatment with each individual

Bacterial effector binding to ribosomal protein s3 subverts NF-kappaB function.

Directory of Open Access Journals (Sweden)

Xiaofei Gao

2009-12-01

Full Text Available Enteric bacterial pathogens cause food borne disease, which constitutes an enormous economic and health burden. Enterohemorrhagic Escherichia coli (EHEC causes a severe bloody diarrhea following transmission to humans through various means, including contaminated beef and vegetable products, water, or through contact with animals. EHEC also causes a potentially fatal kidney disease (hemolytic uremic syndrome for which there is no effective treatment or prophylaxis. EHEC and other enteric pathogens (e.g., enteropathogenic E. coli (EPEC, Salmonella, Shigella, Yersinia utilize a type III secretion system (T3SS to inject virulence proteins (effectors into host cells. While it is known that T3SS effectors subvert host cell function to promote diarrheal disease and bacterial transmission, in many cases, the mechanisms by which these effectors bind to host proteins and disrupt the normal function of intestinal epithelial cells have not been completely characterized. In this study, we present evidence that the E. coli O157:H7 nleH1 and nleH2 genes encode T3SS effectors that bind to the human ribosomal protein S3 (RPS3, a subunit of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB transcriptional complexes. NleH1 and NleH2 co-localized with RPS3 in the cytoplasm, but not in cell nuclei. The N-terminal region of both NleH1 and NleH2 was required for binding to the N-terminus of RPS3. NleH1 and NleH2 are autophosphorylated Ser/Thr protein kinases, but their binding to RPS3 is independent of kinase activity. NleH1, but not NleH2, reduced the nuclear abundance of RPS3 without altering the p50 or p65 NF-kappaB subunits or affecting the phosphorylation state or abundance of the inhibitory NF-kappaB chaperone IkappaBalpha NleH1 repressed the transcription of a RPS3/NF-kappaB-dependent reporter plasmid, but did not inhibit the transcription of RPS3-independent reporters. In contrast, NleH2 stimulated RPS3-dependent transcription, as well

CAPERalpha is a novel Rel-TAD-interacting factor that inhibits lymphocyte transformation by the potent Rel/NF-kappaB oncoprotein v-Rel.

Science.gov (United States)

Dutta, Jui; Fan, Gaofeng; Gélinas, Céline

2008-11-01

The Rel/NF-kappaB transcription factors are constitutively activated in many human cancers. The Rel proteins in this family are implicated in leukemia/lymphomagenesis, but the mechanism is not completely understood. Previous studies showed that the transcription activation domains (TADs) of the viral oncoprotein v-Rel and its cellular Rel/NF-kappaB homologues c-Rel and RelA are key determinants of their different transforming activities in primary lymphocytes. Substitution of a Rel TAD for that of RelA conferred a strong transforming phenotype upon RelA, which otherwise failed to transform cells. To gain insights into protein interactions that influence cell transformation by the Rel TADs, we identified factors that interact with the TAD of v-Rel, the most oncogenic member of the Rel/NF-kappaB family. We report that the coactivator for transcription factors AP-1 and estrogen receptors, CAPERalpha, interacts with the v-Rel TAD and potently synergizes v-Rel-mediated transactivation. Importantly, coexpression of CAPERalpha markedly reduced and delayed v-Rel's transforming activity in primary lymphocytes, whereas a dominant-negative mutant enhanced the kinetics of v-Rel-mediated transformation. Furthermore, small interfering RNA-mediated knockdown of CAPERalpha in v-Rel-transformed lymphocytes significantly enhanced colony formation in soft agar. Since the potency of Rel-mediated transactivation is an important determinant of lymphocyte transformation, as is Rel's ability to induce transcriptional repression, these data suggest that CAPERalpha's interaction with the Rel TAD could modulate Rel/NF-kappaB's transforming activity by facilitating expression or dampening repression of specific gene subsets important for oncogenesis. Overall, this study identifies CAPERalpha as a new transcriptional coregulator for v-Rel and reveals an important role in modulating Rel's oncogenic activity.

Hemin inhibits cyclooxygenase-2 expression through nuclear factor-kappa B activation and ornithine decarboxylase expression in 12-O-tetradecanoylphorbol-13-acetate-treated mouse skin

International Nuclear Information System (INIS)

Park, Jae Hee; Lee, Chang Ki; Hwang, Young Sun; Park, Kwang-Kyun; Chung, Won-Yoon

2008-01-01

Inflammation induced by various stimuli has been found to be associated with increased risk for most types of human cancer. Inflammation facilitates the initiation of normal cells, as well as the growth of initiated cells and their progression to malignancy through production of proinflammatory cytokines and diverse reactive oxygen/nitrogen species. These also activate the signaling molecules that are involved in inflammation and carcinogenesis. Our previous studies have demonstrated that hemin inhibited 7,12-dimethylbenz[a]anthracene (DMBA)-induced bacterial mutagenesis and oxidative DNA damage, reduced the level of DNA-DMBA adduct and 12-O-tetradecanoylphorobl-13-acetate (TPA)-induced tumor formation in DMBA-initiated ICR mouse skin, and inhibited myeloperoxidase and ornithine decarboxylase (ODC) activity and H 2 O 2 formation in TPA-treated mouse skin. In the present study, to further elucidate the molecular mechanisms underlying the chemopreventive activity of hemin, its effect on the expression of ODC and cyclooxygenase (COX)-2, and the activation of nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinases (MAPKs) regulating these proteins were explored in mouse skin with TPA-induced inflammation. Topically applied hemin inhibited ear edema and epidermal thickness in mice treated with TPA. Pretreatment with hemin reduced the expression of ODC and COX-2, and also reduced NF-κB activation in TPA-stimulated mouse skin. In addition, hemin suppressed the TPA-induced activation of extracellular signal-regulated protein kinase (ERK) and p38 MAPK in a dose-dependent manner. Taken together, hemin inhibited TPA-induced COX-2 expression by altering NF-κB signaling pathway via ERK and p38 MAPK, as well as TPA-induced ODC expression in mouse skin. Thereby, hemin may be an attractive candidate for a chemopreventive agent

Inhibitory effects of black pepper (Piper nigrum) extracts and compounds on human tumor cell proliferation, cyclooxygenase enzymes, lipid peroxidation and nuclear transcription factor-kappa-B.

Science.gov (United States)

Liu, Yunbao; Yadev, Vivek R; Aggarwal, Bharat B; Nair, Muraleedharan G

2010-08-01

Black pepper (Piper nigrum) and hot pepper (Capsicum spp.) are widely used in traditional medicines. Although hot Capsicum spp. extracts and its active principles, capsaicinoids, have been linked with anticancer and anti-inflammatory activities, whether black pepper and its active principle exhibit similar activities is not known. In this study, we have evaluated the antioxidant, anti-inflammatory and anticancer activities of extracts and compounds from black pepper by using proinflammatory transcription factor NF-kappaB, COX-1 and -2 enzymes, human tumor cell proliferation and lipid peroxidation (LPO). The capsaicinoids, the alkylamides, isolated from the hot pepper Scotch Bonnet were also used to compare the bioactivities of alkylamides and piperine from black pepper. All compounds derived from black pepper suppressed TNF-induced NF-kappaB activation, but alkyl amides, compound 4 from black pepper and 5 from hot pepper, were most effective. The human cancer cell proliferation inhibitory activities of piperine and alklyl amides in Capsicum and black pepper were dose dependant. The inhibitory concentrations 50% (IC50) of the alklylamides were in the range 13-200 microg/mL. The extracts of black pepper at 200 microg/mL and its compounds at 25 microg/mL inhibited LPO by 45-85%, COX enzymes by 31-80% and cancer cells proliferation by 3.5-86.8%. Overall, these results suggest that black pepper and its constituents like hot pepper, exhibit anti-inflammatory, antioxidant and anticancer activities.

Inhibition of transcription factor NF-kappaB signaling proteins IKKbeta and p65 through specific cysteine residues by epoxyquinone A monomer: correlation with its anti-cancer cell growth activity.

Science.gov (United States)

Liang, Mei-Chih; Bardhan, Sujata; Pace, Emily A; Rosman, Diana; Beutler, John A; Porco, John A; Gilmore, Thomas D

2006-02-28

Transcription factor NF-kappaB is constitutively active in many human chronic inflammatory diseases and cancers. Epoxyquinone A monomer (EqM), a synthetic derivative of the natural product epoxyquinol A, has previously been shown to be a potent inhibitor of tumor necrosis factor-alpha (TNF-alpha)-induced activation of NF-kappaB, but the mechanism by which EqM inhibits NF-kappaB activation was not known. In this report, we show that EqM blocks activation of NF-kappaB by inhibiting two molecular targets: IkappaB kinase IKKbeta and NF-kappaB subunit p65. EqM inhibits TNF-alpha-induced IkappaBalpha phosphorylation and degradation by targeting IKKbeta, and an alanine substitution for Cys179 in the activation loop of IKKbeta makes it resistant to EqM-mediated inhibition. EqM also directly inhibits DNA binding by p65, but not p50; moreover, replacement of Cys38 in p65 with Ser abolishes EqM-mediated inhibition of DNA binding. Pretreatment of cells with reducing agent dithiothreitol dose-dependently reduces EqM-mediated inhibition of NF-kappaB, further suggesting that EqM directly modifies the thiol group of Cys residues in protein targets. Modifications of the exocyclic alkene of EqM substantially reduce EqM's ability to inhibit NF-kappaB activation. In the human SUDHL-4 lymphoma cell line, EqM inhibits both proliferation and NF-kappaB DNA binding, and activates caspase-3 activity. EqM also effectively inhibits the growth of human leukemia, kidney, and colon cancer cell lines in the NCI's tumor cell panel. Among six colon cancer cell lines, those with low amounts of constitutive NF-kappaB DNA-binding activity are generally more sensitive to growth inhibition by EqM. Taken together, these results suggest that EqM inhibits growth and induces cell death in tumor cells through a mechanism that involves inhibition of NF-kappaB activity at multiple steps in the signaling pathway.

An Automation Interface for Kappa PC

DEFF Research Database (Denmark)

Hartvig, Susanne C

1999-01-01

The reports documents an automation interface for Kappa PC. The automation interface can be used to embed Kappa applications in 32-bit Windowsapplications.The interface includes functions for initialising Kappa, for loading an application, for settingvalues, for getting values, and for stopping...

The upregulation of receptor activator NF-kappaB ligand expression by interleukin-1alpha and Porphyromonas endodontalis in human osteoblastic cells.

Science.gov (United States)

Chen, S-C; Huang, F-M; Lee, S-S; Li, M-Z; Chang, Y-C

2009-04-01

To investigate the receptor activator of nuclear factor-kappa B (NF-kappaB) ligand (RANKL) in osteoblastic cells stimulated with inflammatory mediators. The expression of RANKL in human osteoblastic cell line U2OS stimulated by pro-inflammatory cytokine interleukin (IL)-1alpha and black-pigmented bacteria Porphyromonas endodontalis was investigated by Western blot and enzyme-linked immunosorbent assay (ELISA). The significance of the results obtained from control and treated groups was statistically analysed by the paired Student's t-test. IL-1alpha was found to upregulate RANKL production in U2OS cells (P endodontalis also increased RANKL expression in U2OS cells after 4-h incubation period demonstrated by Western blot and ELISA (P endodontalis may be involved in developing apical periodontitis through the stimulation of RANKL production.

SIRT1 overexpression decreases cisplatin-induced acetylation of NF-{kappa}B p65 subunit and cytotoxicity in renal proximal tubule cells

Energy Technology Data Exchange (ETDEWEB)

Jung, Yu Jin; Lee, Jung Eun; Lee, Ae Sin [Department of Internal Medicine, Chonbuk National University Medical School, Jeonju (Korea, Republic of); Kang, Kyung Pyo; Lee, Sik; Park, Sung Kwang [Department of Internal Medicine, Chonbuk National University Medical School, Jeonju (Korea, Republic of); Institute for Medical Sciences, Chonbuk National University Medical School, Jeonju (Korea, Republic of); Lee, Sang Yong [Department of Diagnostic Radiology, Chonbuk National University Medical School, Jeonju (Korea, Republic of); Institute for Medical Sciences, Chonbuk National University Medical School, Jeonju (Korea, Republic of); Han, Myung Kwan [Department of Microbiology, Institute for Medical Sciences, Chonbuk National University Medical School, Jeonju (Korea, Republic of); Kim, Duk Hoon [Division of Forensic Medicine, National Forensic Service, Seoul (Korea, Republic of); Kim, Won, E-mail: kwon@jbnu.ac.kr [Department of Internal Medicine, Chonbuk National University Medical School, Jeonju (Korea, Republic of); Institute for Medical Sciences, Chonbuk National University Medical School, Jeonju (Korea, Republic of)

2012-03-09

Highlights: Black-Right-Pointing-Pointer Cisplatin increases acetylation of NF-{kappa}B p65 subunit in HK2 cells. Black-Right-Pointing-Pointer SIRT1 overexpression decreases cisplatin-induced p65 acetylation and -cytotoxicity. Black-Right-Pointing-Pointer Resveratrol decreased cisplatin-induced cell viability through deacetylation of p65. -- Abstract: As the increased acetylation of p65 is linked to nuclear factor-{kappa}B (NF-{kappa}B) activation, the regulation of p65 acetylation can be a potential target for the treatment of inflammatory injury. Cisplatin-induced nephrotoxicity is an important issue in chemotherapy of cancer patients. SIRT1, nicotinamide adenine dinucleotide (NAD{sup +})-dependent protein deacetylase, has been implicated in a variety of cellular processes such as inflammatory injury and the control of multidrug resistance in cancer. However, there is no report on the effect of SIRT1 overexpression on cisplatin-induced acetylation of p65 subunit of NF-{kappa}B and cell injury. To investigate the effect of SIRT1 in on cisplatin-induced acetylation of p65 subunit of NF-{kappa}B and cell injury, HK2 cells were exposed with SIRT1 overexpression, LacZ adenovirus or dominant negative adenovirus after treatment with cisplatin. While protein expression of SIRT1 was decreased by cisplatin treatment compared with control buffer treatment, acetylation of NF-{kappa}B p65 subunit was significantly increased after treatment with cisplatin. Overexpression of SIRT1 ameliorated the increased acetylation of p65 of NF-{kappa}B during cisplatin treatment and cisplatin-induced cytotoxicity. Further, treatment of cisplatin-treated HK2 cells with resveratrol, a SIRT1 activator, also decreased acetylation of NF-{kappa}B p65 subunit and cisplatin-induced increase of the cell viability in HK2 cells. Our findings suggests that the regulation of acetylation of p65 of NF-{kappa}B through SIRT1 can be a possible target to attenuate cisplatin-induced renal cell damage.

Effect of nuclear factor kappa B on intercellular adhesion molecule-1 expression and neutrophil infiltration in lung injury induced by intestinal ischemia/reperfusion in rats

Science.gov (United States)

Tian, Xiao-Feng; Yao, Ji-Hong; Li, Ying-Hua; Zhang, Xue-Song; Feng, Bing-An; Yang, Chun-Ming; Zheng, Shu-Sen

2006-01-01

AIM: To investigate the role of nuclear factor kappa B (NF-κB) in the pathogenesis of lung injury induced by intestinal ischemia/reperfusion (I/R), and its effect on intercellular adhesion molecule-1 (ICAM-1) expression and neutrophil infiltration. METHODS: Twenty-four Wistar rats were divided randomly into control, I/R and pyrrolidine dithiocarbamate (PDTC) treatment groups, n = 8 in each. I/R group and PDTC treatment group received superior mysenteric artery (SMA) occluding for 1 h and reperfusion for 2 h. PDTC group was administrated with intraperitoneal injection of 2% 100 mg/kg PDTC 1 h before surgery. Lung histology and bronchia alveolus lung fluid (BALF) protein were assayed. Serum IL-6, lung malondialdehyde (MDA) and myeloperoxidase (MPO) as well as the expression level of NF-κB and ICAM-1 were measured. RESULTS: Lung injury induced by intestinal I/R, was characterized by edema, hemorrhage and neutrophil infiltration as well as by the significant rising of BALF protein. Compared to control group, the levels of serum IL-6 and lung MDA and MPO increased significantly in I/R group (P = 0.001). Strong positive expression of NF-κB p65 and ICAM-1 was observed. After the administration of PDTC, the level of serum IL-6, lung MDA and MPO as well as NF-κB and ICAM-1 decreased significantly (P < 0.05) when compared to I/R group. CONCLUSION: The activation of NF-κB plays an important role in the pathogenesis of lung injury induced by intestinal I/R through upregulating the neutrophil infiltration and lung ICAM-1 expression. PDTC as an inhibitor of NF-κB can prevent lung injury induced by intestinal I/R through inhibiting the activity of NF-κB. PMID:16489637

The disagreeable behaviour of the kappa statistic.

Science.gov (United States)

Flight, Laura; Julious, Steven A

2015-01-01

It is often of interest to measure the agreement between a number of raters when an outcome is nominal or ordinal. The kappa statistic is used as a measure of agreement. The statistic is highly sensitive to the distribution of the marginal totals and can produce unreliable results. Other statistics such as the proportion of concordance, maximum attainable kappa and prevalence and bias adjusted kappa should be considered to indicate how well the kappa statistic represents agreement in the data. Each kappa should be considered and interpreted based on the context of the data being analysed. Copyright © 2014 John Wiley & Sons, Ltd.

Stevioside ameliorates high-fat diet-induced insulin resistance and adipose tissue inflammation by downregulating the NF-{kappa}B pathway

Energy Technology Data Exchange (ETDEWEB)

Wang, Zhiquan; Xue, Liqiong; Guo, Cuicui; Han, Bing; Pan, Chunming; Zhao, Shuangxia; Song, Huaidong [State Key Laboratory of Medical Genomics, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025 (China); Ma, Qinyun, E-mail: qinyunma@126.com [State Key Laboratory of Medical Genomics, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025 (China)

2012-01-27

Highlights: Black-Right-Pointing-Pointer Stevioside ameliorates high-fat diet-induced insulin resistance. Black-Right-Pointing-Pointer Stevioside alleviates the adipose tissue inflammation. Black-Right-Pointing-Pointer Stevioside reduces macrophages infiltration into the adipose tissue. Black-Right-Pointing-Pointer Stevioside suppresses the activation of NF-{kappa}B in the adipose tissue. -- Abstract: Accumulating evidence suggests that adipose tissue is the main source of pro-inflammatory molecules that predispose individuals to insulin resistance. Stevioside (SVS) is a widely used sweetener with multiple beneficial effects for diabetic patients. In this study, we investigated the effect of SVS on insulin resistance and the pro-inflammatory state of adipose tissue in mice fed with a high-fat diet (HFD). Oral administration of SVS for 1 month had no effect on body weight, but it significantly improved fasting glucose, basal insulin levels, glucose tolerance and whole body insulin sensitivity. Interestingly, these changes were accompanied with decreased expression levels of several inflammatory cytokines in adipose tissue, including TNF-{alpha}, IL6, IL10, IL1{beta}, KC, MIP-1{alpha}, CD11b and CD14. Moreover, macrophage infiltration in adipose tissue was remarkably reduced by SVS. Finally, SVS significantly suppressed the nuclear factor-kappa b (NF-{kappa}B) signaling pathway in adipose tissue. Collectively, these results suggested that SVS may ameliorate insulin resistance in HFD-fed mice by attenuating adipose tissue inflammation and inhibiting the NF-{kappa}B pathway.

Characterization of kappa 1 and kappa 2 opioid binding sites in frog (Rana esculenta) brain membrane preparation

Energy Technology Data Exchange (ETDEWEB)

Benyhe, S.; Varga, E.; Hepp, J.; Magyar, A.; Borsodi, A.; Wollemann, M.

1990-09-01

The distribution and properties of frog brain kappa-opioid receptor subtypes differ not only from those of the guinea pig brain, but also from that of the rat brain. In guinea pig cerebellum the kappa 1 is the dominant receptor subtype, frog brain contains mainly the kappa 2 subtype, and the distribution of the rat brain subtypes is intermediate between the two others. In competition experiments it has been established that ethylketocyclazocine and N-cyclopropylmethyl-norazidomorphine, which are nonselective kappa-ligands, have relatively high affinities to frog brain membranes. The kappa 2 ligands (Met5)enkephalin-Arg6-Phe7 and etorphine also show high affinities to the frog brain. Kappa 1 binding sites measured in the presence of 5 microM/D-Ala2-Leu5/enkephalin represent 25-30% of (3H)ethylketocyclazocine binding in frog brain membranes. The kappa 2 subtype in frog brain resembles more to the mu subtype than the delta subtype of opioid receptors, but it differs from the mu subtype in displaying low affinity toward beta-endorphin and /D-Ala2-(Me)Phe4-Gly5-ol/enkephalin (DAGO). From our data it is evident that the opioid receptor subtypes are already present in the amphibian brain but the differences among them are less pronounced than in mammalian brain.

Characterization of kappa 1 and kappa 2 opioid binding sites in frog (Rana esculenta) brain membrane preparation

International Nuclear Information System (INIS)

Benyhe, S.; Varga, E.; Hepp, J.; Magyar, A.; Borsodi, A.; Wollemann, M.

1990-01-01

The distribution and properties of frog brain kappa-opioid receptor subtypes differ not only from those of the guinea pig brain, but also from that of the rat brain. In guinea pig cerebellum the kappa 1 is the dominant receptor subtype, frog brain contains mainly the kappa 2 subtype, and the distribution of the rat brain subtypes is intermediate between the two others. In competition experiments it has been established that ethylketocyclazocine and N-cyclopropylmethyl-norazidomorphine, which are nonselective kappa-ligands, have relatively high affinities to frog brain membranes. The kappa 2 ligands (Met5)enkephalin-Arg6-Phe7 and etorphine also show high affinities to the frog brain. Kappa 1 binding sites measured in the presence of 5 microM/D-Ala2-Leu5/enkephalin represent 25-30% of [3H]ethylketocyclazocine binding in frog brain membranes. The kappa 2 subtype in frog brain resembles more to the mu subtype than the delta subtype of opioid receptors, but it differs from the mu subtype in displaying low affinity toward beta-endorphin and /D-Ala2-(Me)Phe4-Gly5-ol/enkephalin (DAGO). From our data it is evident that the opioid receptor subtypes are already present in the amphibian brain but the differences among them are less pronounced than in mammalian brain

Human xenospecific T suppressor cells inhibit T helper cell proliferation to porcine aortic endothelial cells, and NF-kappaB activity in porcine APC.

Science.gov (United States)

Ciubotariu, R; Li, J; Colovai, A I; Platt, J L; Cortesini, R; Suciu Foca Cortesini, N

2001-05-01

Human T suppressor cells (Ts), capable of preventing autologous T helper cells (Th) from reacting against xenogeneic pig endothelial cells and pig APC can be generated in vitro. Ts derive from a population of CD3(+)CD8(+)CD28(-) T lymphocytes and specifically recognize the MHC class I antigens of the APC used for in vitro immunization. To study the mechanism that underlies suppression, we investigated whether Ts inhibit the expression of costimulatory molecules in xenogeneic professional and semiprofessional APC. We found that Ts down-regulate Th-induced expression of CD86 in pig APC, and that this effect occurs at the level of transcription, as indicated by nuclear run-on and Northern blot assays. EMSA results revealed that inhibition of CD86 expression is mediated by inactivation of transcription factor NF-kappaB. Furthermore, transfection of pig APC with a vector expressing NF-kappaB p65 partially rescued Th-induced expression of the CD86 molecule. These results strongly support the concept that xenospecific Ts inhibit the APC function of xenogeneic cells by preventing activation of NF-kappaB.

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.

Mapping the transcription termination region of the mouse immunoglobulin kappa gene

International Nuclear Information System (INIS)

Xu, M.; Garrard, W.T.

1986-01-01

To define the transcription termination region of the mouse immunoglobulin kappa gene, they have subcloned single copy DNA sequences corresponding to both the template and the non-template strands of this locus. In vitro nuclear transcription with isolated MPC-11 nuclei was performed and the resulting 32 P-labeled RNA was hybridized to slot-blotted, single-stranded M13 probes covering regions within and flanking the kappa gene. The hybridization pattern for the template-strand reveals that transcription terminates within the region between 1.1 to 2.3 kb downstream from the poly(A) site. Ten different short sequences (8-13 bp) reside within 460 bp of this region that exhibit homology with sequences found in the termination regions of mouse β-globin and chicken ovalbumin genes. Transcription of the non-template strand occurs on either side of this termination region. They note that no transcription is detectable on the non-template strand downstream of the enhancer, indicating that if RNA polymerase II enters at this site, it does not initiate transcription during transit to the promoter region. They conclude that transcription of the kappa gene passes the poly(A) addition site and terminates within 2.3 Kb downstream

Association of Activation of Induced COX-2, iNOS and Cytokines with NF-kappa B Depression by Taiwan Wild Grape Ethanolic Extract in Mice.

Science.gov (United States)

Chang, Ching-Wen; Chen, Yi-Han; Lin, Yu-Chin; Peng, Wen-Huang

2017-08-31

Taiwan wild grape (Vitis thunbergii var. taiwaniana; VTT) is an important traditional herbal medicine used to treat muscle injuries and acute and chronic pain of the ligaments. Information on its bioactivity and the underlying mechanisms, which have not been elucidated thus far, is needed to demonstrate its value for pharmacological and clinical use. This study presents evidence to clarify the antinociceptive and anti-inflammatory activities of an ethanolic extract of VTT stem (VTTEtOH) and the possible molecular mechanisms involved in such biactivities. In the mice, VTTEtOH significantly reduced the acetic acid-induced writhing response (P < 0.01), formalin-induced licking time (P < 0.01), and edema paw volume at 4 and 5 h after λ-carrageenan injection. VTTEtOH obviously decreased the levels of tumor necrosis factor alpha (P < 0.01), interleukin (IL)-1β (P < 0.05), interleukin (IL)-6 (P < 0.001), nuclear factor-kappa B (P < 0.001), iNOS (P < 0.001), cyclooxygenase-2 (P < 0.001) and Nitric oxide (P < 0.001) in edema-paw tissue. The molecular mechanisms underlying these effects might involve significant inhibition of the activity of cyclooxygenase-2 through suppression of nuclear factor-kappa B and inducible nitric oxide synthase expression and reduction of the levels of various inflammatory mediators, including tumor necrosis factor alpha, interleukin (IL)-1β, IL-6, and nitric oxide. Our findings provided pharmacological and histopathological evidences that VTTEtOH alleviates inflammatory pain-related diseases.

{kappa}-deformed realization of D=4 conformal algebra

Energy Technology Data Exchange (ETDEWEB)

Klimek, M. [Technical Univ. of Czestochowa, Inst. of Mathematics and Computer Science, Czestochowa (Poland); Lukierski, J. [Universite de Geneve, Department de Physique Theorique, Geneve (Switzerland)

1995-07-01

We describe the generators of {kappa}-conformal transformations, leaving invariant the {kappa}-deformed d`Alembert equation. In such a way one obtains the conformal extension of-shell spin spin zero realization of {kappa}-deformed Poincare algebra. Finally the algebraic structure of {kappa}-deformed conformal algebra is discussed. (author). 23 refs.

TGF-{beta}1 increases invasiveness of SW1990 cells through Rac1/ROS/NF-{kappa}B/IL-6/MMP-2

Energy Technology Data Exchange (ETDEWEB)

Binker, Marcelo G. [Departments of Medicine and Physiology, University of Toronto, Toronto, Ontario, Canada M5S 1A8 (Canada); CBRHC Research Center, Buenos Aires (Argentina); Binker-Cosen, Andres A. [CBRHC Research Center, Buenos Aires (Argentina); Gaisano, Herbert Y. [Departments of Medicine and Physiology, University of Toronto, Toronto, Ontario, Canada M5S 1A8 (Canada); Cosen, Rodica H. de [CBRHC Research Center, Buenos Aires (Argentina); Cosen-Binker, Laura I., E-mail: laura.cosen.binker@utoronto.ca [Departments of Medicine and Physiology, University of Toronto, Toronto, Ontario, Canada M5S 1A8 (Canada); CBRHC Research Center, Buenos Aires (Argentina)

2011-02-04

Research highlights: {yields} Rac1 mediates TGF-{beta}1-induced SW1990 invasion through MMP-2 secretion and activation. {yields} NADPH-generated ROS act downstream of Rac1 in TGF-{beta}1-challenged SW1990 cells. {yields} TGF-{beta}1-stimulated ROS activate NF-{kappa}B in SW1990 cells. {yields} NF{kappa}B-induced IL-6 release is required for secretion and activation of MMP-2 in SW1990 cells. -- Abstract: Human pancreatic cancer invasion and metastasis have been found to correlate with increased levels of active matrix metalloproteinase 2 (MMP-2). The multifunctional cytokine transforming growth factor beta 1 (TGF-{beta}1) has been shown to increase both secretion of MMP-2 and invasion by several pancreatic cancer cell types. In the present study, we investigated the signaling pathway involved in TGF-{beta}1-promoted MMP-2 secretion and invasion by human pancreatic cancer cells SW1990. Using specific inhibitors, we found that stimulation of these tumor cells with TGF-{beta}1 induced secretion and activation of the collagenase MMP-2, which was required for TGF-{beta}1-stimulated invasion. Our results also indicate that signaling events involved in TGF-{beta}1-enhanced SW1990 invasiveness comprehend activation of Rac1 followed by generation of reactive oxygen species through nicotinamide adenine dinucleotide phosphate-oxidase, activation of nuclear factor-kappa beta, release of interleukin-6, and secretion and activation of MMP-2.

Oryza sativa (Rice) Hull Extract Inhibits Lipopolysaccharide-Induced Inflammatory Response in RAW264.7 Macrophages by Suppressing Extracellular Signal-regulated Kinase, c-Jun N-terminal Kinase, and Nuclear Factor-κB Activation.

Science.gov (United States)

Ha, Sang Keun; Sung, Jeehye; Choi, Inwook; Kim, Yoonsook

2016-01-01

Rice ( Oryza sativa ) is a major cereal crop in many Asian countries and an important staple food source. Rice hulls have been reported to possess antioxidant activities. In this study, we evaluated the antiinflammatory effects of rice hull extract and associated signal transduction mechanisms in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. We found that rice hull extract inhibited nitric oxide (NO) and prostaglandin E 2 by suppressing the expression of inducible NO synthase and cyclooxygenase-2, respectively. The release of interleukin-1β and tumor necrosis factor-α was also reduced in a dose-dependent manner. Furthermore, rice hull extract attenuated the activation of nuclear factor-kappa B (NF-κB), as well as the phosphorylation of mitogen-activated protein kinases, extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK), in LPS-stimulated RAW264.7 cells. This suggests that rice hull extract decreases the production of inflammatory mediators by downregulating ERK and JNK and the NF-κB signal pathway in RAW 264.7 cells. Rice hull extract inhibits the lipopolysaccharide-induced inflammatory response in RAW264.7 macrophages.Rice hull extract inhibited nitric oxide and prostaglandin E 2 by suppressing the expression of inducible NO synthase and cyclooxygenase-2, respectively.Rice hull extract exerted anti-inflammatory effect through inhibition of nuclear factor-kappa B, extracellular signal-regulated kinase and c-Jun N-terminal kinase signaling pathways.Rice hull extract may provide a potential therapeutic approach for inflammatory diseases. Abbreviations used: COX-2: cyclooxygenase-2, ERK: extracellular signal-regulated kinase, IκB: inhibitory kappa B, IL-1β: interleukin-1β, iNOS: inducible NO synthase, JNK: c-Jun N-terminal kinase, LPS: lipopolysaccharide, MAPKs: mitogen-activated protein kinases, NF-κB: nuclear factor-κB, NO: nitric oxide, PGE2: prostaglandin E2, RHE: rice hull extract, ROS: reactive oxygen species

Is a gene important for bone resorption a candidate for obesity? An association and linkage study on the RANK (receptor activator of nuclear factor-kappaB) gene in a large Caucasian sample.

Science.gov (United States)

Zhao, Lan-Juan; Guo, Yan-Fang; Xiong, Dong-Hai; Xiao, Peng; Recker, Robert R; Deng, Hong-Wen

2006-11-01

In light of findings that osteoporosis and obesity may share some common genetic determination and previous reports that RANK (receptor activator of nuclear factor-kappaB) is expressed in skeletal muscles which are important for energy metabolism, we hypothesize that RANK, a gene essential for osteoclastogenesis, is also important for obesity. In order to test the hypothesis with solid data we first performed a linkage analysis around the RANK gene in 4,102 Caucasian subjects from 434 pedigrees, then we genotyped 19 SNPs in or around the RANK gene. A family-based association test (FBAT) was performed with both a quantitative measure of obesity [fat mass, lean mass, body mass index (BMI), and percentage fat mass (PFM)] and a dichotomously defined obesity phenotype-OB (OB if BMI > or = 30 kg/m(2)). In the linkage analysis, an empirical P = 0.004 was achieved at the location of the RANK gene for BMI. Family-based association analysis revealed significant associations of eight SNPs with at least one obesity-related phenotype (P obesity phenotype. The P value is 0.126 for OB, 0.033 for fat mass, 0.021 for lean mass, 0.016 for BMI, and 0.006 for PFM. The haplotype data analyses provide further association evidence. In conclusion, for the first time, our results suggest that RANK is a novel candidate for determination of obesity.

Angle Kappa and its importance in refractive surgery

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Majid Moshirfar

2013-01-01

Full Text Available Angle kappa is the difference between the pupillary and visual axis. This measurement is of paramount consideration in refractive surgery, as proper centration is required for optimal results. Angle kappa may contribute to MFIOL decentration and its resultant photic phenomena. Adjusting placement of MFIOLs for angle kappa is not supported by the literature but is likely to help reduce glare and haloes. Centering LASIK in angle kappa patients over the corneal light reflex is safe, efficacious, and recommended. Centering in-between the corneal reflex and the entrance pupil is also safe and efficacious. The literature regarding PRK in patients with an angle kappa is sparse but centering on the corneal reflex is assumed to be similar to centering LASIK on the corneal reflex. Thus, centration of MFIOLs, LASIK, and PRK should be focused on the corneal reflex for patients with a large angle kappa. More research is needed to guide surgeons′ approach to angle kappa.

Preliminary Estimation of Kappa Parameter in Croatia

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Stanko, Davor; Markušić, Snježana; Ivančić, Ines; Mario, Gazdek; Gülerce, Zeynep

2017-12-01

Spectral parameter kappa κ is used to describe spectral amplitude decay “crash syndrome” at high frequencies. The purpose of this research is to estimate spectral parameter kappa for the first time in Croatia based on small and moderate earthquakes. Recordings of local earthquakes with magnitudes higher than 3, epicentre distances less than 150 km, and focal depths less than 30 km from seismological stations in Croatia are used. The value of kappa was estimated from the acceleration amplitude spectrum of shear waves from the slope of the high-frequency part where the spectrum starts to decay rapidly to a noise floor. Kappa models as a function of a site and distance were derived from a standard linear regression of kappa-distance dependence. Site kappa was determined from the extrapolation of the regression line to a zero distance. The preliminary results of site kappa across Croatia are promising. In this research, these results are compared with local site condition parameters for each station, e.g. shear wave velocity in the upper 30 m from geophysical measurements and with existing global shear wave velocity - site kappa values. Spatial distribution of individual kappa’s is compared with the azimuthal distribution of earthquake epicentres. These results are significant for a couple of reasons: to extend the knowledge of the attenuation of near-surface crust layers of the Dinarides and to provide additional information on the local earthquake parameters for updating seismic hazard maps of studied area. Site kappa can be used in the re-creation, and re-calibration of attenuation of peak horizontal and/or vertical acceleration in the Dinarides area since information on the local site conditions were not included in the previous studies.

Increased levels of NOTCH1, NF-kappaB, and other interconnected transcription factors characterize primitive sets of hematopoietic stem cells.

Science.gov (United States)

Panepucci, Rodrigo Alexandre; Oliveira, Lucila Habib B; Zanette, Dalila Luciola; Viu Carrara, Rita de Cassia; Araujo, Amélia Goes; Orellana, Maristela Delgado; Bonini de Palma, Patrícia Vianna; Menezes, Camila C B O; Covas, Dimas Tadeu; Zago, Marco Antonio

2010-03-01

As previously shown, higher levels of NOTCH1 and increased NF-kappaB signaling is a distinctive feature of the more primitive umbilical cord blood (UCB) CD34+ hematopoietic stem cells (HSCs), as compared to bone marrow (BM). Differences between BM and UCB cell composition also account for this finding. The CD133 marker defines a more primitive cell subset among CD34+ HSC with a proposed hemangioblast potential. To further evaluate the molecular basis related to the more primitive characteristics of UCB and CD133+ HSC, immunomagnetically purified human CD34+ and CD133+ cells from BM and UCB were used on gene expression microarrays studies. UCB CD34+ cells contained a significantly higher proportion of CD133+ cells than BM (70% and 40%, respectively). Cluster analysis showed that BM CD133+ cells grouped with the UCB cells (CD133+ and CD34+) rather than to BM CD34+ cells. Compared with CD34+ cells, CD133+ had a higher expression of many transcription factors (TFs). Promoter analysis on all these TF genes revealed a significantly higher frequency (than expected by chance) of NF-kappaB-binding sites (BS), including potentially novel NF-kappaB targets such as RUNX1, GATA3, and USF1. Selected transcripts of TF related to primitive hematopoiesis and self-renewal, such as RUNX1, GATA3, USF1, TAL1, HOXA9, HOXB4, NOTCH1, RELB, and NFKB2 were evaluated by real-time PCR and were all significantly positively correlated. Taken together, our data indicate the existence of an interconnected transcriptional network characterized by higher levels of NOTCH1, NF-kappaB, and other important TFs on more primitive HSC sets.

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.

Glycogen Synthase Kinase 3α Is the Main Isoform That Regulates the Transcription Factors Nuclear Factor-Kappa B and cAMP Response Element Binding in Bovine Endothelial Cells Infected with Staphylococcus aureus

Directory of Open Access Journals (Sweden)

Octavio Silva-García

2018-01-01

Full Text Available Glycogen synthase kinase 3 (GSK3 is a constitutive enzyme implicated in the regulation of cytokine expression and the inflammatory response during bacterial infections. Mammals have two GSK3 isoforms named GSK3α and GSK3β that plays different but often overlapping functions. Although the role of GSK3β in cytokine regulation during the inflammatory response caused by bacteria is well described, GSK3α has not been found to participate in this process. Therefore, we tested if GSK3α may act as a regulatory isoform in the cytokine expression by bovine endothelial cells infected with Staphylococcus aureus because this bacterium is one of the major pathogens that cause tissue damage associated with inflammatory dysfunction. Interestingly, although both isoforms were phosphorylated–inactivated, we consistently observed a higher phosphorylation of GSK3α at Ser21 than that of GSK3β at Ser9 after bacterial challenge. During a temporal course of infection, we characterized a molecular switch from pro-inflammatory cytokine expression (IL-8, promoted by nuclear factor-kappa B (NF-κB, at an early stage (2 h to an anti-inflammatory cytokine expression (IL-10, promoted by cAMP response element binding (CREB, at a later stage (6 h. We observed an indirect effect of GSK3α activity on NF-κB activation that resulted in a low phosphorylation of CREB at Ser133, a decreased interaction between CREB and the co-activator CREB-binding protein (CBP, and a lower expression level of IL-10. Gene silencing of GSK3α and GSK3β with siRNA indicated that GSK3α knockout promoted the interaction between CREB and CBP that, in turn, increased the expression of IL-10, reduced the interaction of NF-κB with CBP, and reduced the expression of IL-8. These results indicate that GSK3α functions as the primary isoform that regulates the expression of IL-10 in endothelial cells infected with S. aureus.

Andrographolide interferes with binding of nuclear factor-κB to DNA in HL-60-derived neutrophilic cells

Science.gov (United States)

Hidalgo, María A; Romero, Alex; Figueroa, Jaime; Cortés, Patricia; Concha, Ilona I; Hancke, Juan L; Burgos, Rafael A

2005-01-01

Andrographolide, the major active component from Andrographis paniculata, has shown to possess anti-inflammatory activity. Andrographolide inhibits the expression of several proinflammatory proteins that exhibit a nuclear factor kappa B (NF-κB) binding site in their gene. In the present study, we analyzed the effect of andrographolide on the activation of NF-κB induced by platelet-activating factor (PAF) and N-formyl-methionyl-leucyl-phenylalanine (fMLP) in HL-60 cells differentiated to neutrophils. PAF (100 nM) and fMLP (100 nM) induced activation of NF-κB as determined by degradation of inhibitory factor B α (IκBα) using Western blotting in cytosolic extracts and by binding to DNA using electrophoretic mobility shift assay (EMSA) in nuclear extracts. Andrographolide (5 and 50 μM) inhibited the NF-κB-luciferase activity induced by PAF. However, andrographolide did not reduce phosphorylation of p38 MAPK or ERK1/2 and did not change IκBα degradation induced by PAF and fMLP. Andrographolide reduced the DNA binding of NF-κB in whole cells and in nuclear extracts induced by PAF and fMLP. Andrographolide reduced cyclooxygenase-2 (COX-2) expression induced by PAF and fMLP in HL-60/neutrophils. It is concluded that andrographolide exerts its anti-inflammatory effects by inhibiting NF-κB binding to DNA, and thus reducing the expression of proinflammatory proteins, such as COX-2. PMID:15678086

Measurement of the Parameter Kappa, and Reevaluation of Kappa for Small to Moderate Earthquakes at Seismic Stations in the Vicinity of Yucca Mountain, Nevada

International Nuclear Information System (INIS)

Biasi, Glenn; Anderson, John G

2007-01-01

The parameter kappa was defined by Anderson and Hough (1984) to describe the high-frequency spectral roll-off of the strong motion seismic spectrum. In the work of Su et al., (1996) the numerical value of kappa estimated for sites near Yucca Mountain was small (∼20 ms). The estimate obtained from these events has been applied through a rigorous methodology to develop design earthquake spectra with magnitude over 5.0. Smaller values of kappa lead to higher estimated ground motions in the methodology used by the Probabilistic Seismic Hazard Analysis (PSHA) for Yucca Mountain. An increase of 10 ms in kappa could result in a substantial decrease in the high frequency level of the predicted ground motions. Any parameter that plays such a critical role deserves close examination. Here, we study kappa and its associated uncertainties. The data set used by Su et al (1996) consisted of 12 M 2.8 to 4.5 earthquakes recorded at temporary stations deployed after the June 1992 Little Skull Mountain earthquake. The kappa elements of that study were revisited by Anderson and Su (MOL.20071203.0134) and substantially confirmed. One weakness of those studies is the limited data used. Few of these stations were on tuff or on Yucca Mountain itself. A decade of Southern Great Basin Digital Seismic Network (SGBDSN) recording has now yielded a larger body of on-scale, well calibrated digital ground motion records suitable for investigating kappa. We use the SGBDSN data to check some of the original assumptions, improve the statistical confidence of the conclusions, and determine values of kappa for stations on or near Yucca Mountain. The outstanding issues in kappa analysis, as they apply to Yucca Mountain, include: (1) The number itself. The kappa estimate near 20 msec from Su et al. (1996) and Anderson and Su (MOL.20071203.0134) is markedly smaller than is considered typical in California (Silva, 1995). The low kappa value has engineering consequences because when it is applied in

Measurement of the Parameter Kappa, and Reevaluation of Kappa for Small to Moderate Earthquakes at Seismic Stations in the Vicinity of Yucca Mountain, Nevada

Energy Technology Data Exchange (ETDEWEB)

Biasi, Glenn; Anderson, John G

2007-12-05

The parameter kappa was defined by Anderson and Hough (1984) to describe the high-frequency spectral roll-off of the strong motion seismic spectrum. In the work of Su et al., (1996) the numerical value of kappa estimated for sites near Yucca Mountain was small (~20 ms). The estimate obtained from these events has been applied through a rigorous methodology to develop design earthquake spectra with magnitude over 5.0. Smaller values of kappa lead to higher estimated ground motions in the methodology used by the Probabilistic Seismic Hazard Analysis (PSHA) for Yucca Mountain. An increase of 10 ms in kappa could result in a substantial decrease in the high frequency level of the predicted ground motions. Any parameter that plays such a critical role deserves close examination. Here, we study kappa and its associated uncertainties. The data set used by Su et al (1996) consisted of 12 M 2.8 to 4.5 earthquakes recorded at temporary stations deployed after the June 1992 Little Skull Mountain earthquake. The kappa elements of that study were revisited by Anderson and Su (MOL.20071203.0134) and substantially confirmed. One weakness of those studies is the limited data used. Few of these stations were on tuff or on Yucca Mountain itself. A decade of Southern Great Basin Digital Seismic Network (SGBDSN) recording has now yielded a larger body of on-scale, well calibrated digital ground motion records suitable for investigating kappa. We use the SGBDSN data to check some of the original assumptions, improve the statistical confidence of the conclusions, and determine values of kappa for stations on or near Yucca Mountain. The outstanding issues in kappa analysis, as they apply to Yucca Mountain, include: 1. The number itself. The kappa estimate near 20 msec from Su et al. (1996) and Anderson and Su (MOL.20071203.0134) is markedly smaller than is considered typical in California (Silva, 1995). The low kappa value has engineering consequences because when it is applied in ground

Measurement of Angle Kappa Using Ultrasound Biomicroscopy and Corneal Topography.

Science.gov (United States)

Yeo, Joon Hyung; Moon, Nam Ju; Lee, Jeong Kyu

2017-06-01

To introduce a new convenient and accurate method to measure the angle kappa using ultrasound biomicroscopy (UBM) and corneal topography. Data from 42 eyes (13 males and 29 females) were analyzed in this study. The angle kappa was measured using Orbscan II and calculated with UBM and corneal topography. The angle kappa of the dominant eye was compared with measurements by Orbscan II. The mean patient age was 36.4 ± 13.8 years. The average angle kappa measured by Orbscan II was 3.98° ± 1.12°, while the average angle kappa calculated with UBM and corneal topography was 3.19° ± 1.15°. The difference in angle kappa measured by the two methods was statistically significant (p topography to calculate the angle kappa. This method is convenient to use and allows for measurement of the angle kappa without an expensive device. © 2017 The Korean Ophthalmological Society

Scalar field propagation in the phi^4 kappa-Minkowski model

OpenAIRE

Meljanac, S.; Samsarov, A.; Trampetic, J.; Wohlgenannt, M.

2011-01-01

In this article we use the noncommutative (NC) kappa-Minkowski phi^4 model based on the kappa-deformed star product, ({*}_h). The action is modified by expanding up to linear order in the kappa-deformation parameter a, producing an effective model on commutative spacetime. For the computation of the tadpole diagram contributions to the scalar field propagation/self-energy, we anticipate that statistics on the kappa-Minkowski is specifically kappa-deformed. Thus our prescription in fact repres...

Azadirachtin interacts with the tumor necrosis factor (TNF) binding domain of its receptors and inhibits TNF-induced biological responses.

Science.gov (United States)

Thoh, Maikho; Kumar, Pankaj; Nagarajaram, Hampathalu A; Manna, Sunil K

2010-02-19

The role of azadirachtin, an active component of a medicinal plant Neem (Azadirachta indica), on TNF-induced cell signaling in human cell lines was investigated. Azadirachtin blocks TNF-induced activation of nuclear factor kappaB (NF-kappaB) and also expression of NF-kappaB-dependent genes such as adhesion molecules and cyclooxygenase 2. Azadirachtin inhibits the inhibitory subunit of NF-kappaB (IkappaB alpha) phosphorylation and thereby its degradation and RelA (p65) nuclear translocation. It blocks IkappaB alpha kinase (IKK) activity ex vivo, but not in vitro. Surprisingly, azadirachtin blocks NF-kappaB DNA binding activity in transfected cells with TNF receptor-associated factor (TRAF)2, TNF receptor-associated death domain (TRADD), IKK, or p65, but not with TNFR, suggesting its effect is at the TNFR level. Azadirachtin blocks binding of TNF, but not IL-1, IL-4, IL-8, or TNF-related apoptosis-inducing ligand (TRAIL) with its respective receptors. Anti-TNFR antibody or TNF protects azadirachtin-mediated down-regulation of TNFRs. Further, in silico data suggest that azadirachtin strongly binds in the TNF binding site of TNFR. Overall, our data suggest that azadirachtin modulates cell surface TNFRs thereby decreasing TNF-induced biological responses. Thus, azadirachtin exerts an anti-inflammatory response by a novel pathway, which may be beneficial for anti-inflammatory therapy.

Kappa-Electrons Downstream of the Solar Wind Termination Shock

Science.gov (United States)

Fahr, H. J.

2017-12-01

A theoretical description of the solar wind electron distribution function downstream of the termination shock under the influence of the shock-induced injection of overshooting KeV-energetic electrons will be presented. A kinetic phasespace transport equation in the bulk frame of the heliosheath plasma flow is developed for the solar wind electrons, taking into account shock-induced electron injection, convective changes, magnetic cooling processes and whistler wave-induced energy diffusion. Assuming that the local electron distribution under the prevailing Non-LTE conditions can be represented by a local kappa function with a local kappa parameter that varies with the streamline coordinates, we determine the parameters of the resulting, initial kappa distribution for the downstream electrons. From this initial function spectral electron fluxes can be derived and can be compared with those measured by the VOYAGER-1 spacecraft in the range between 40 to 70 KeV. It can then be shown that with kappa values around kappa = 6 one can in fact fit these data very satisfactorily. In addition it is shown that for isentropic electron flows kappa-distributed electrons have to undergo simultaneous changes of both parameters, i.e. kappa and theta, of the electron kappa function. It is also shown then that under the influence of energy sinks and sources the electron flux becomes non-isentropic with electron entropies changing along the streamline.

Persistent activation of NF-kappaB related to IkappaB's degradation profiles during early chemical hepatocarcinogenesis

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García-Román Rebeca

2007-04-01

Full Text Available Abstract Background To define the NF-kappaB activation in early stages of hepatocarcinogenesis and its IkappaB's degradation profiles in comparison to sole liver regeneration. Methods Western-blot and EMSA analyses were performed for the NF-kappaB activation. The transcriptional activity of NF-kappaB was determined by RT-PCR of the IkappaB-α mRNA. The IkappaB's degradation proteins were determined by Western-blot assay. Results We demonstrated the persistent activation of NF-kappaB during early stages of hepatocarcinogenesis, which reached maximal level 30 min after partial hepatectomy. The DNA binding and transcriptional activity of NF-kappaB, were sustained during early steps of hepatocarcinogenesis in comparison to only partial hepatectomy, which displayed a transitory NF-kappaB activation. In early stages of hepatocarconogenesis, the IkappaB-α degradation turned out to be acute and transitory, but the low levels of IkappaB-β persisted even 15 days after partial hepatectomy. Interestingly, IkappaB-β degradation is not induced after sole partial hepatectomy. Conclusion We propose that during liver regeneration, the transitory stimulation of the transcription factor response, assures blockade of NF-kappaB until recovery of the total mass of the liver and the persistent NF-kappaB activation in early hepatocarcinogenesis may be due to IkappaB-β and IkappaB-α degradation, mainly IkappaB-β degradation, which contributes to gene transcription related to proliferation required for neoplasic progression.

Nonequilibrium approach regarding metals from a linearised kappa distribution

Science.gov (United States)

Domenech-Garret, J. L.

2017-10-01

The widely used kappa distribution functions develop high-energy tails through an adjustable kappa parameter. The aim of this work is to show that such a parameter can itself be regarded as a function, which entangles information about the sources of disequilibrium. We first derive and analyse an expanded Fermi-Dirac kappa distribution. Later, we use this expanded form to obtain an explicit analytical expression for the kappa parameter of a heated metal on which an external electric field is applied. We show that such a kappa index causes departures from equilibrium depending on the physical magnitudes. Finally, we study the role of temperature and electric field on such a parameter, which characterises the electron population of a metal out of equilibrium.

Bmi-1 promotes the aggressiveness of glioma via activating the NF-kappaB/MMP-9 signaling pathway

International Nuclear Information System (INIS)

Jiang, Lili; Wu, Jueheng; Yang, Yi; Liu, Liping; Song, Libing; Li, Jun; Li, Mengfeng

2012-01-01

The prognosis of human glioma is poor, and the highly invasive nature of the disease represents a major impediment to current therapeutic modalities. The oncoprotein B-cell-specific Moloney murine leukemia virus integration site 1 protein (Bmi-1) has been linked to the development and progression of glioma; however, the biological role of Bmi-1 in the invasion of glioma remains unclear. A172 and LN229 glioma cells were engineered to overexpress Bmi-1 via stable transfection or to be silenced for Bmi-1 expression using RNA interfering method. Migration and invasiveness of the engineered cells were assessed using wound healing assay, Transwell migration assay, Transwell matrix penetration assay and 3-D spheroid invasion assay. MMP-9 expression and activity were measured using real-time PCR, ELISA and the gelatin zymography methods. Expression of NF-kappaB target genes was quantified using real-time PCR. NF-kappaB transcriptional activity was assessed using an NF-kappaB luciferase reporter system. Expression of Bmi-1 and MMP-9 in clinical specimens was analyzed using immunohistochemical assay. Ectopic overexpression of Bmi-1 dramatically increased, whereas knockdown of endogenous Bmi-1 reduced, the invasiveness and migration of glioma cells. NF-kappaB transcriptional activity and MMP-9 expression and activity were significantly increased in Bmi-1-overexpressing but reduced in Bmi-1-silenced cells. The reporter luciferase activity driven by MMP-9 promoter in Bmi-1-overexpressing cells was dependent on the presence of a functional NF-kappaB binding site, and blockade of NF-kappaB signaling inhibited the upregulation of MMP-9 in Bmi-1 overexpressing cells. Furthermore, expression of Bmi-1 correlated with NF-kappaB nuclear translocation as well as MMP-9 expression in clinical glioma samples. Bmi-1 may play an important role in the development of aggressive phenotype of glioma via activating the NF-kappaB/MMP-9 pathway and therefore might represent a novel therapeutic

Bmi-1 promotes the aggressiveness of glioma via activating the NF-kappaB/MMP-9 signaling pathway

Directory of Open Access Journals (Sweden)

Jiang Lili

2012-09-01

Full Text Available Abstract Background The prognosis of human glioma is poor, and the highly invasive nature of the disease represents a major impediment to current therapeutic modalities. The oncoprotein B-cell-specific Moloney murine leukemia virus integration site 1 protein (Bmi-1 has been linked to the development and progression of glioma; however, the biological role of Bmi-1 in the invasion of glioma remains unclear. Methods A172 and LN229 glioma cells were engineered to overexpress Bmi-1 via stable transfection or to be silenced for Bmi-1 expression using RNA interfering method. Migration and invasiveness of the engineered cells were assessed using wound healing assay, Transwell migration assay, Transwell matrix penetration assay and 3-D spheroid invasion assay. MMP-9 expression and activity were measured using real-time PCR, ELISA and the gelatin zymography methods. Expression of NF-kappaB target genes was quantified using real-time PCR. NF-kappaB transcriptional activity was assessed using an NF-kappaB luciferase reporter system. Expression of Bmi-1 and MMP-9 in clinical specimens was analyzed using immunohistochemical assay. Results Ectopic overexpression of Bmi-1 dramatically increased, whereas knockdown of endogenous Bmi-1 reduced, the invasiveness and migration of glioma cells. NF-kappaB transcriptional activity and MMP-9 expression and activity were significantly increased in Bmi-1-overexpressing but reduced in Bmi-1-silenced cells. The reporter luciferase activity driven by MMP-9 promoter in Bmi-1-overexpressing cells was dependent on the presence of a functional NF-kappaB binding site, and blockade of NF-kappaB signaling inhibited the upregulation of MMP-9 in Bmi-1 overexpressing cells. Furthermore, expression of Bmi-1 correlated with NF-kappaB nuclear translocation as well as MMP-9 expression in clinical glioma samples. Conclusions Bmi-1 may play an important role in the development of aggressive phenotype of glioma via activating the NF-kappa

Nonplanar ion acoustic waves with kappa-distributed electrons

International Nuclear Information System (INIS)

Sahu, Biswajit

2011-01-01

Using the standard reductive perturbation technique, nonlinear cylindrical and spherical Kadomtsev-Petviashvili equations are derived for the propagation of ion acoustic solitary waves in an unmagnetized collisionless plasma with kappa distributed electrons and warm ions. The influence of kappa-distributed electrons and the effects caused by the transverse perturbation on cylindrical and spherical ion acoustic waves (IAWs) are investigated. It is observed that increase in the kappa distributed electrons (i.e., decreasing κ) decreases the amplitude of the solitary electrostatic potential structures. The numerical results are presented to understand the formation of ion acoustic solitary waves with kappa-distributed electrons in nonplanar geometry. The present investigation may have relevance in the study of propagation of IAWs in space and laboratory plasmas.

Moderate extracellular acidification inhibits capsaicin-induced cell death through regulating calcium mobilization, NF-{kappa}B translocation and ROS production in synoviocytes

Energy Technology Data Exchange (ETDEWEB)

Hu, Fen; Yang, Shuang; Zhao, Dan; Zhu, Shuyan; Wang, Yuxiang [Department of Biophysics, School of Physics and Key Laboratory of Bioactive Materials of Education Ministry, Nankai University, Tianjin 300071 (China); Li, Junying, E-mail: jyli04@nankai.edu.cn [Department of Biophysics, School of Physics and Key Laboratory of Bioactive Materials of Education Ministry, Nankai University, Tianjin 300071 (China)

2012-07-20

Highlights: Black-Right-Pointing-Pointer Moderate extracellular acidification regulates intracellular Ca{sup 2+} mobilization. Black-Right-Pointing-Pointer Moderate acidification activates NF-{kappa}B nuclear translocation in synoviocytes. Black-Right-Pointing-Pointer Moderate acidification depresses the ROS production induced by capsaicin. Black-Right-Pointing-Pointer Moderate acidification inhibits capsaicin-caused synoviocyte death. -- Abstract: We previously show the expression of transient receptor potential vanilloid 1 (TRPV1) in primary synoviocytes from collagen-induced arthritis (CIA) rats. Capsaicin and lowered extracellular pH from 7.4 to 5.5 induce cell death through TRPV1-mediated Ca{sup 2+} entry and reactive oxygen species (ROS) production. However, under the pathological condition in rheumatoid arthritis, the synovial fluid is acidified to a moderate level (about pH 6.8). In the present study, we examined the effects of pH 6.8 on the TRPV1-mediated cell death. Our finding is different or even opposite from what was observed at pH 5.5. We found that the moderate extracellular acidification (from pH 7.4 to 6.8) inhibited the capsaicin-induced Ca{sup 2+} entry through attenuating the activity of TRPV1. In the mean time, it triggered a phospholipse C (PLC)-related Ca{sup 2+} release from intracellular stores. The nuclear translocation of NF-{kappa}B was found at pH 6.8, and this also depends on PLC activation. Moreover, the capsaicin-evoked massive ROS production and cell death were depressed at pH 6.8, both of which are dependent on the activation of PLC and NF-{kappa}B. Taken together, these results suggested that the moderate extracellular acidification inhibited the capsaicin-induced synoviocyte death through regulating Ca{sup 2+} mobilization, activating NF-{kappa}B nuclear translocation and depressing ROS production.

Numerical solution of High-kappa model of superconductivity

Energy Technology Data Exchange (ETDEWEB)

Karamikhova, R. [Univ. of Texas, Arlington, TX (United States)

1996-12-31

We present formulation and finite element approximations of High-kappa model of superconductivity which is valid in the high {kappa}, high magnetic field setting and accounts for applied magnetic field and current. Major part of this work deals with steady-state and dynamic computational experiments which illustrate our theoretical results numerically. In our experiments we use Galerkin discretization in space along with Backward-Euler and Crank-Nicolson schemes in time. We show that for moderate values of {kappa}, steady states of the model system, computed using the High-kappa model, are virtually identical with results computed using the full Ginzburg-Landau (G-L) equations. We illustrate numerically optimal rates of convergence in space and time for the L{sup 2} and H{sup 1} norms of the error in the High-kappa solution. Finally, our numerical approximations demonstrate some well-known experimentally observed properties of high-temperature superconductors, such as appearance of vortices, effects of increasing the applied magnetic field and the sample size, and the effect of applied constant current.

NIK and IKKbeta interdependence in NF-kappaB signalling--flux analysis of regulation through metabolites.

Science.gov (United States)

Kim, Hong-Bum; Evans, Iona; Smallwood, Rod; Holcombe, Mike; Qwarnstrom, Eva E

2010-02-01

Activation of the transcription factor NF-kappaB is central to control of immune and inflammatory responses. Cytokine induced activation through the classical or canonical pathway relies on degradation of the inhibitor, IkappaBalpha and regulation by the IKKbeta kinase. In addition, the NF-kappaB is activated through the NF-kappaB-inducing kinase, NIK. Analysis of the IKK/NIK inter-relationship and its impact on NF-kappaB control, were analysed by mathematical modelling, using matrix formalism and stoichiometrically balanced reactions. The analysis considered a range of bio-reactions and core metabolites and their role in relation to kinase activation and in control of specific steps of the NF-kappaB pathway. The model predicts a growth-rate and time-dependent transfer of the primary kinase activity from IKKbeta to NIK. In addition, it suggests that NIK/IKKbeta interdependence is controlled by intermediates of phosphoribosylpyrophosphate (PRPP) within the glycolysis pathway, and thus, identifies a link between specific metabolic events and kinase activation in inflammatory signal transduction. Subsequent in vitro experiments, carried out to validate the impact of IKK/NIK interdependence, confirmed signal amplification at the level of the NF-kappaB/IkappaBalpha complex control in the presence of both kinases. Further, they demonstrate that the induced potentiation is due to synergistic enhancement of relA-dependent activation. Copyright (c) 2009 Elsevier Ireland Ltd. All rights reserved.

Agmatine inhibits nuclear factor-κB nuclear translocation in acute spinal cord compression injury rat model

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Doaa M. Samy

2016-09-01

Full Text Available Secondary damage after acute spinal cord compression injury (SCCI exacerbates initial insult. Nuclear factor kappa-B (NF-κB-p65 activation is involved in SCCI deleterious effects. Agmatine (Agm showed neuroprotection against various CNS injuries. However, Agm impact on NF-κB signaling in acute SCCI remains to be investigated. The present study compared the effectiveness of Agm therapy and decompression laminectomy (DL in functional recovery, oxidative stress, inflammatory and apoptotic responses, and modulation of NF-κB activation in acute SCCI rat model. Rats were either sham-operated or subjected to SCCI at T8–9, using 2-Fr. catheter. SCCI rats were randomly treated with DL at T8–9, intraperitoneal Agm (100 mg/kg/day, combined (DL/Agm treatment or saline (n = 16/group. After 28-days of neurological follow-up, spinal cords were either subjected to biochemical measurement of oxidative stress and inflammatory markers or histopathology and immuno-histochemistry for NF-κB-p65 and caspase-3 expression (n = 8/group. Agm was comparable to DL in facilitating neurological functions recovery, reducing inflammation (TNF-α/interleukin-6, and apoptosis. Agm was distinctive in combating oxidative stress. Agm neuroprotective effects were paralleled with inhibition of NF-κB-p65 nuclear translocation. Combined pharmacological and surgical interventions were proved superior in functional recovery. In conclusion, present research suggested a new mechanism for Agm neuroprotection in rats SCCI through inhibition of NF-κB activation.

ESTUDIO PRELIMINAR SOBRE LA INFLUENCIA DE LA CARRAGENINA KAPPA, KAPPA I.II Y GOMA TARA EN LA VISCOSIDAD Y TIXOTROPÍA DE LAS SALMUERAS DE INYECCIÓN PARA JAMONES COCIDOS PICADOS DE CERDO PRELIMINARY STUDY ON THE INFLUENCE OF KAPPA, KAPPA I.II CARRAGEENAN AND TARA GUM IN THE VISCOSITY AND THIXOTROPY OF INJECTION BRINES FOR COOKED CHOPPED HAMS OF PORK

Directory of Open Access Journals (Sweden)

Fabio Alexander Molina Cote

2010-12-01

Full Text Available El presente estudio determinó el efecto que sobre la viscosidad y la tixotropía de una salmuera de masajeo para jamones picados cocidos de cerdo, tiene la adición de carragenina kappa, carragenina kappa I.II y goma tara, cuando son usadas a un nivel del 1% en la salmuera. Para tal efecto se incorporaron seis mezclas distintas de hidrocoloides provenientes de la carragenina kappa, kappa I.II y goma tara (individualmente, en mezclas binarias y mezclas terciarias, en una salmuera de inyección y masajeo para jamones; a las cuales se les determinó su comportamiento viscoso y tixotrópico a 4 ºC. Los datos obtenidos de índice de tixotropía (máximos, se analizaron mediante un modelo cuadrático derivado de un arreglo de mezclas. Los resultados mostraron que todas las salmueras se comportaron tixotrópicamente, presentando mayor área de histéresis, las mezclas que contenían goma tara. El modelo usado para el índice de tixotropía arrojó, con un nivel de significancia de 0,05, que la relación óptima, es la que contiene la mezcla de carragenina kappa I.II-goma tara (79% y 21%. Adicionalmente, las salmueras que contenían carragenina kappa, carragenina kappa I.II y carragenina kappa-carragenina kappa I.II presentaron menor viscosidad que las mezclas que contenían goma tara.The aim of this study was to determine the thixotropy´s effect of a massage brine in cooked chopped pork hams with addition of kappa, kappa I.II carrageenan, tara gum and their mixtures, when were used at 1% injection level of brine to meat. Six mixtures were evaluated. A protocol for thixotropy measurement adjusted to the conditions of brines used taking in account salinity, pH, temperature and shear stress. Data obtained from thixotropy index (maximum were analyzed with quadratic model derived from blends array. Results showed thixotropic measurement to brines presented a very small area, showing structural changes, but with very fast recovery. It was observed

Ion-cyclotron instability in plasmas described by product-bi-kappa distributions

International Nuclear Information System (INIS)

Santos, M. S. dos; Ziebell, L. F.; Gaelzer, R.

2015-01-01

The dispersion relation for parallel propagating waves in the ion-cyclotron branch is investigated numerically by considering that the velocity distribution of the ion population is a function of type product-bi-kappa. We investigate the effects of the non-thermal features and of the anisotropy associated with this type of distribution on the ion-cyclotron instability, as well as the influence of different forms of the electron distribution, by considering Maxwellian distributions, bi-kappa distributions, and product-bi-kappa distributions. The cases of ions described by either Maxwellian or bi-kappa distributions are also considered, for comparison. The results of the numerical analysis show that the increase in the non-thermal character associated with the anisotropic kappa distributions for ions contributes to enhance the instability as compared to that obtained in the Maxwellian case, in magnitude and in wave number range, with more significant enhancement for the case of ion product-bi-kappa distributions than for the case of ion bi-kappa distributions. It is also shown that the ion-cyclotron instability is decreased if the electrons are described by product-bi-kappa distributions, while electrons described by bi-kappa distributions lead to growth rates which are very similar to those obtained considering a Maxwellian distribution for the electron population

Class A scavenger receptor promotes osteoclast differentiation via the enhanced expression of receptor activator of NF-{kappa}B (RANK)

Energy Technology Data Exchange (ETDEWEB)

Takemura, Kenichi [Department of Cell Pathology, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-8556 (Japan); Department of Orthopaedic and Neuro-Musculoskeletal Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto (Japan); Sakashita, Naomi; Fujiwara, Yukio; Komohara, Yoshihiro; Lei, XiaoFeng; Ohnishi, Koji [Department of Cell Pathology, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-8556 (Japan); Suzuki, Hiroshi [National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Hokkaido (Japan); Kodama, Tatsuhiko [Department of Molecular Biology and Medicine, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo (Japan); Mizuta, Hiroshi [Department of Orthopaedic and Neuro-Musculoskeletal Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto (Japan); Takeya, Motohiro, E-mail: takeya@kumamoto-u.ac.jp [Department of Cell Pathology, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-8556 (Japan)

2010-01-22

Osteoclasts originate from bone marrow monocyte/macrophage lineage cells, and their differentiation depends on macrophage colony-stimulating factor (M-CSF) and receptor activator nuclear factor kappa B (RANK) ligand. Class A scavenger receptor (SR-A) is one of the principal functional molecules of macrophages, and its level of expression declines during osteoclast differentiation. To investigate the role of SR-A in osteoclastogenesis, we examined pathological changes in femoral bone and the expression levels of osteoclastogenesis-related molecules in SR-A{sup -/-} mice. The femoral osseous density of SR-A{sup -/-} mice was higher than that of SR-A{sup +/+} mice, and the number of multinucleated osteoclasts was significantly decreased. An in vitro differentiation assay revealed that the differentiation of multinucleated osteoclasts from bone marrow-derived progenitor cells is impaired in SR-A{sup -/-} mice. Elimination of SR-A did not alter the expression level of the M-CSF receptor, c-fms; however, the expression levels of RANK and RANK-related osteoclast-differentiation molecules such as nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1 (NFATc1) and microphthalmia-associated transcription factor (MITF) significantly decreased. Furthermore, acetylated low-density lipoprotein (AcLDL), an SR-A ligand, significantly increased the expression level of RANK and MITF during osteoclast differentiation. These data indicate that SR-A promotes osteoclastogenesis via augmentation of the expression level of RANK and its related molecules.

Pim-2 activates API-5 to inhibit the apoptosis of hepatocellular carcinoma cells through NF-kappaB pathway.

Science.gov (United States)

Ren, Ke; Zhang, Wei; Shi, Yujun; Gong, Jianping

2010-06-01

Pim-2 is proved to be relevant to the tumorigenesis of hepatocellular carcinoma (HCC), but the mechanism is unclear. We studied the relationship among Pim-2, NF-kappaB and API-5. In our experiment, expression level of the three factors and phosphorylation level of API-5, as well as NF-kappaB activity, were detected in HCC tissues and the nontumorous controls. Then Pim-2 gene was transfected into nontumorous liver cells L02, and Pim-2 SiRNA was transfected into hepatoblastoma cell line HepG2. Parthenolide was added as NF-kappaB inhibitor. The same detections as above were repeated in the cells, along with the apoptosis analysis. We found the levels of Pim-2, NF-kappaB and API-5, as well as NF-kappaB activity, were significantly higher in HCC tissues. Pim-2 level was increased in L02 cells after the transfection of Pim-2 gene, but decreased in HepG2 cells after the transfection of Pim-2 SiRNA. The levels of NF-kappaB and API-5, as well as NF-kappaB activity and API-5 phosphorylation level, were in accordance with Pim-2 level, but could be reversed by Parthenolide. Cell apoptosis rates were negatively correlated with API-5 phosphorylation level. Therefore, we infer that Pim-2 could activate API-5 to inhibit the apoptosis of liver cells, and NF-kappaB is the key regulator.

NIK is involved in constitutive activation of the alternative NF-{kappa}B pathway and proliferation of pancreatic cancer cells

Energy Technology Data Exchange (ETDEWEB)

Nishina, Takashi [Division of Cellular and Molecular Biology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639 (Japan); Yamaguchi, Noritaka [Division of Cellular and Molecular Biology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639 (Japan); Consolidated Research Institute for Advanced Science and Medical Care, Waseda University, 513 Wasedatsurumaki-cho, Shinjuku-ku, Tokyo 162-0041 (Japan); Gohda, Jin [Division of Cellular and Molecular Biology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639 (Japan); Semba, Kentaro [Consolidated Research Institute for Advanced Science and Medical Care, Waseda University, 513 Wasedatsurumaki-cho, Shinjuku-ku, Tokyo 162-0041 (Japan); Department of Life Science and Medical Bio-science, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480 (Japan); Inoue, Jun-ichiro, E-mail: jun-i@ims.u-tokyo.ac.jp [Division of Cellular and Molecular Biology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639 (Japan)

2009-10-09

Pancreatic cancer has one of the poorest prognoses among human neoplasms. Constitutive activation of NF-{kappa}B is frequently observed in pancreatic cancer cells and is involved in their malignancy. However, little is known about the molecular mechanism of this constitutive NF-{kappa}B activation. Here, we show that the alternative pathway is constitutively activated and NF-{kappa}B-inducing kinase (NIK), a mediator of the alternative pathway, is significantly expressed in pancreatic cancer cells. siRNA-mediated silencing of NIK expression followed by subcellular fractionation revealed that NIK is constitutively involved in the processing of p100 and nuclear transport of p52 and RelB in pancreatic cancer cells. In addition, NIK silencing significantly suppressed proliferation of pancreatic cancer cells. These results clearly indicate that NIK is involved in the constitutive activation of the alternative pathway and controls cell proliferation in pancreatic cancer cells. Therefore, NIK might be a novel target for the treatment of pancreatic cancer.

JANEX-1, a JAK3 inhibitor, protects pancreatic islets from cytokine toxicity through downregulation of NF-{kappa}B activation and the JAK/STAT pathway

Energy Technology Data Exchange (ETDEWEB)

Lv, Na; Kim, Eun-Kyung; Song, Mi-Young [Department of Biochemistry, Medical School and Diabetes Research Center, Chonbuk National University, Jeonju, Jeonbuk 561-756 (Korea, Republic of); Choi, Ha-Na; Moon, Woo Sung [Department of Pathology, Medical School and Diabetes Research Center, Chonbuk National University, Jeonju, Jeonbuk 561-756 (Korea, Republic of); Park, Sung-Joo [Department of Herbology, School of Oriental Medicine, Wonkwang University, Iksan, Jeonbuk 570-749 (Korea, Republic of); Park, Jin-Woo [Department of Biochemistry, Medical School and Diabetes Research Center, Chonbuk National University, Jeonju, Jeonbuk 561-756 (Korea, Republic of); Kwon, Kang-Beom, E-mail: desson@wonkwang.ac.kr [Department of Physiology, School of Oriental Medicine, Wonkwang University, Iksan, Jeonbuk 570-749 (Korea, Republic of); Park, Byung-Hyun, E-mail: bhpark@chonbuk.ac.kr [Department of Biochemistry, Medical School and Diabetes Research Center, Chonbuk National University, Jeonju, Jeonbuk 561-756 (Korea, Republic of)

2009-07-15

JANEX-1/WHI-P131, a selective Janus kinase 3 (JAK3) inhibitor, has been shown to delay the onset of diabetes in the NOD mouse model. However, the molecular mechanism by which JANEX-1 protects pancreatic {beta}-cells is unknown. In the current study, we investigated the role of JANEX-1 on interleukin (IL)-1{beta} and interferon (IFN)-{gamma}-induced {beta}-cell damage using isolated islets. JANEX-1-pretreated islets showed resistance to cytokine toxicity, namely suppressed nitric oxide (NO) production, reduced inducible form of NO synthase (iNOS) expression, and decreased islet destruction. The molecular mechanism by which JANEX-1 inhibits iNOS expression was mediated through suppression of the nuclear factor {kappa}B (NF-{kappa}B) and JAK/signal transducer and activator of transcription (STAT) pathways. Islets treated with the cytokines downregulated the protein levels of suppressor of cytokine signaling (SOCS)-1 and SOCS-3, but pretreatment with JANEX-1 attenuated these decreases. Additionally, islets from JAK3{sup -/-} mice were more resistant to cytokine toxicity than islets from control mice. These results demonstrate that JANEX-1 protects {beta}-cells from cytokine toxicity through suppression of the NF-{kappa}B and JAK/STAT pathways and upregulation of SOCS proteins, suggesting that JANEX-1 may be used to preserve functional {beta}-cell mass.

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.

Interleukin-1/toll-like receptor-induced nuclear factor kappa B signaling participates in intima hyperplasia after carotid artery balloon injury in goto-kakizaki rats: a potential target therapy pathway.

Directory of Open Access Journals (Sweden)

Xiaotian Zhang

Full Text Available The value of restenosis after percutaneous coronary intervention (PCI is recognized worldwide, especially for diabetic patients. Interleukin-1/Toll-like receptor (IL-1/TLR signaling is involved in innate and adaptive immune responses, but whether and how the IL-1/TLR-induced nuclear factor kappa B (NFκB pathway plays key roles in intimal formation is unclear. The underlying mechanism of intima hyperplasia was investigated with a model of carotid balloon injury in Goto-Kakizaki (GK and Wistar rats and with lipopolysaccharide-stimulated macrophages. Elastic-van Gieson staining showed the medial area peakedon Day 3 post-injury and decreased by Day 7 post-injury in both GK and Wistar rats. The N/M at Day 7 in GK rats was significantly higher than in Wistar rats (p<0.001. The percent of 5-ethynyl-2'-deoxyuridine (EdU staining-positive cells on Day 3 post-injury was greater than seen on Day 7 post-injury in GK and Wistar rats. The percent of EdU-positive cells on Days 3 and 7 post-injury in Wistar rats was less than that found in GK rats (p<0.01; p<0.05. NFκBp65 immunostaining had increased by Day 7 post-injury. Agilent Whole Genome Oligo Microarray verified that the IL-1/TLR-induced NFκB pathway was activated by carotid balloon injury. TLR4, IL-1 receptor associated kinase, inhibitors α of NFκB, human antigen R, c-Myc (Proto-Oncogene Proteins, EGF-like module-containing mucin-like hormone receptor-like 1 and Interleukin-6 were up-regulated or down-regulated according to immunochemistry, quantitative real-time PCR, Western blotting and Enzyme linked immunosorbent assay. Overall, we conclude that the IL-1/TLR-induced NFκB pathway participates in the intimal hyperplasia after carotid injury in GK and Wistar rats and that GK rats respond more intensely to the inflammation than Wistar rats.

Human factors in nuclear power plants

International Nuclear Information System (INIS)

Swain, A.D.

1981-01-01

This report describes some of the human factors problems in nuclear power plants and the technology that can be employed to reduce those problems. Many of the changes to improve the human factors in existing plants are inexpensive, and the expected gain in human reliability is substantial. The human factors technology is well-established and there are practitioners in most countries that have nuclear power plants. (orig.) [de

Insertion of a nuclear factor kappa B DNA nuclear-targeting sequence potentiates suicide gene therapy efficacy in lung cancer cell lines

DEFF Research Database (Denmark)

Cramer, F; Christensen, C L; Poulsen, T T

2012-01-01

Lung cancer currently causes the majority of cancer-related deaths worldwide and new treatments are in high demand. Gene therapy could be a promising treatment but currently lacks sufficient efficiency for clinical use, primarily due to limited cellular and nuclear DNA delivery. In the present...

Factors affecting nuclear development

International Nuclear Information System (INIS)

Stevens, G.H.; Girouard, P.

1995-01-01

Among the factors affecting nuclear development, some depend more or less on public authorities, but many are out of public authorities control (foreign policies, market and deregulation, socials and environmental impacts, public opinion). As far as possible, the following study tries to identify those factors. (D.L.). 2 photos

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.

Ultraviolet inactivation and photoreactivation of the cholera phage 'Kappa'

International Nuclear Information System (INIS)

Samad, S.A.; Bhattacharyya, S.C.; Chatterjee, S.N.

1987-01-01

The lysogenic cholera phage, 'Kappa' is some ten to twenty folds more resistant to UV (254 nm) than are most of the T. phages of E. coli, or the cholera phage PL 163/10, or the host V. cholerae strain H218 Sm r , the 37% (D 37 ) and 10% (D 10 ) survival doses being 255.8 J/m 2 and 633.6 J/m 2 respectively. The UV-irradiated 'Kappa' phages could be photoreactivated in the host V. cholerae strain H218 Sm r to a maximum extent of 40%. The removal of the number of lethal hits per phage by the survival-enhancement treatment (photoreactivation) with time followed an exponential relation, the constant probability of removal of lethal hit per unit time being 2.8x10 -2 min -1 . The UV-irradiated phages could also be Weigle reactivated in the host strain of H218 Sm r by a small degree, the maximum reactivation factor (ratio of survivals in UV-irradiated and non-irradiated hosts) being 1.50. (orig.)

Power peaking nuclear reliability factors

International Nuclear Information System (INIS)

Hassan, H.A.; Pegram, J.W.; Mays, C.W.; Romano, J.J.; Woods, J.J.; Warren, H.D.

1977-11-01

The Calculational Nuclear Reliability Factor (CNRF) assigned to the limiting power density calculated in reactor design has been determined. The CNRF is presented as a function of the relative power density of the fuel assembly and its radial local. In addition, the Measurement Nuclear Reliability Factor (MNRF) for the measured peak hot pellet power in the core has been evaluated. This MNRF is also presented as a function of the relative power density and radial local within the fuel assembly

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

Directory of Open Access Journals (Sweden)

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.

The NF-kappa B inhibitor, celastrol, could enhance the anti-cancer effect of gambogic acid on oral squamous cell carcinoma

International Nuclear Information System (INIS)

He, Di; Chen, Wantao; Xu, Qin; Yan, Ming; Zhang, Ping; Zhou, Xiaojian; Zhang, Zhiyuan; Duan, Wenhu; Zhong, Laiping; Ye, Dongxia

2009-01-01

Gambogic acid (GA) is a major active ingredient of gamboge, a widely used traditional Chinese medicine that has been reported to be a potent cytotoxic agent against some malignant tumors. Many studies have shown that the NF-kappa B signaling pathway plays an important role in anti-apoptosis and the drug resistance of tumor cells during chemotherapy. In this study, the effects and mechanisms of GA and the NF-kappa B inhibitor celastrol on oral cancer cells were investigated. Three human oral squamous cell carcinoma cell lines, Tca8113, TSCC and NT, were treated with GA alone, celastrol alone or GA plus celastrol. Cytotoxicity was assessed by MTT assay. The rate of apoptosis was examined with annexin V/PI staining as well as transmission electronic microscopy in Tca8113 cells. The level of constitutive NF-kappa B activity in oral squamous cell carcinoma cell lines was determined by immunofluorescence assays and nuclear extracts and electrophoretic mobility shift assays (EMSAs) in vitro. To further investigate the role of NF-kappa B activity in GA and celastrol treatment in oral squamous cell carcinoma, we used the dominant negative mutant SR-IκBα to inhibit NF-kappa B activity and to observe its influence on the effect of GA. The results showed that GA could inhibit the proliferation and induce the apoptosis of the oral squamous cell carcinoma cell lines and that the NF-kappa B pathway was simultaneously activated by GA treatment. The minimal cytotoxic dose of celastrol was able to effectively suppress the GA-induced NF-kappa B pathway activation. Following the combined treatment with GA and the minimal cytotoxic dose of celastrol or the dominant negative mutant SR-IκBα, proliferation was significantly inhibited, and the apoptotic rate of Tca8113 cells was significantly increased. The combination of GA and celastrol has a synergistic antitumor effect. The effect can be primarily attributed to apoptosis induced by a decrease in NF-kappa B pathway activation. The

X-ray inactivation and reactivation characteristics of the phage 'kappa'

International Nuclear Information System (INIS)

Bhattacharyya, S.C.; Samad, S.A.; Mandal, J.C.; Chatterjee, S.N.

1991-01-01

Vibrio cholerae temperate phage 'kappa' was inactivated by X-ray (60 kV) in a dose dependent manner, the inactivation dose leading to 37% survival (D 37 ) in PBS, pH 7.4 being 0.36 kGy. The phages were significantly protected against X-ray irradiation when histidine or cysteine or both were present in PBS or when phages were irradiated in nutrient broth. The maximum protection was offered when histidine (10.0 nM) and cysteine (10.0 nM) were both present in PBS (dose enhancement factor being 4.17). The X-irradiated 'kappa' phages also underwent a small but significant Weigle reactivation and also Weigle mutagenesis in the UV-irradiated V. cholerae host H218Sm r . The Weigle factor (WF) or the frequency of clear plaque mutants increased with increasing UV dose, attained a maximum at the UV dose of 2.4 Jm -2 and thereafter decreased gradually with further increase of UV dose. The X-ray dose (D)-survival (S) curves could be empirically described by the equation S=exp-(aD+bD 2 ) where 'a' and 'b' are constants depending on the irradiation conditions and good agreement between the theoretical curves and experimental data was obtained. (author). 1 5 refs., 2 fig., 1 tab

Kappa. -electron capture probability in sup 167 Tm

Energy Technology Data Exchange (ETDEWEB)

Sree Krishna Murty, G.; Chandrasekhar Rao, M.V.S.; Radha Krishna, K.; Bhuloka Reddy, S.; Satyanarayana, G.; Ramana Rao, P.V.; Sastry, D.L. (Andhra Univ., Visakhapatnam (India). Labs. for Nuclear Research); Chintalapudi, S.N. (Variable Energy Cyclotron Centre, Calcutta (India))

1990-07-01

The {Kappa}-electron capture probability in the decay of {sup 167}Tm for the first-forbidden transition 1/2{sup +}{yields}3/2{sup -} was measured using the sum-coincidence method and employing a hyper-pure Ge system. The P{sub {Kappa}} value is found to be 0.835{plus minus}0.029, in agreement with the theoretical value of 0.829. (author).

Kappa statistic for clustered matched-pair data.

Science.gov (United States)

Yang, Zhao; Zhou, Ming

2014-07-10

Kappa statistic is widely used to assess the agreement between two procedures in the independent matched-pair data. For matched-pair data collected in clusters, on the basis of the delta method and sampling techniques, we propose a nonparametric variance estimator for the kappa statistic without within-cluster correlation structure or distributional assumptions. The results of an extensive Monte Carlo simulation study demonstrate that the proposed kappa statistic provides consistent estimation and the proposed variance estimator behaves reasonably well for at least a moderately large number of clusters (e.g., K ≥50). Compared with the variance estimator ignoring dependence within a cluster, the proposed variance estimator performs better in maintaining the nominal coverage probability when the intra-cluster correlation is fair (ρ ≥0.3), with more pronounced improvement when ρ is further increased. To illustrate the practical application of the proposed estimator, we analyze two real data examples of clustered matched-pair data. Copyright © 2014 John Wiley & Sons, Ltd.

NF-kappa B modulation is involved in celastrol induced human multiple myeloma cell apoptosis.

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Haiwen Ni

Full Text Available Celastrol is an active compound extracted from the root bark of the traditional Chinese medicine Tripterygium wilfordii Hook F. To investigate the effect of celastrol on human multiple myeloma cell cycle arrest and apoptosis and explore its molecular mechanism of action. The activity of celastrol on LP-1 cell proliferation was detected by WST-8 assay. The celastrol-induced cell cycle arrest was analyzed by flow cytometry after propidium iodide staining. Nuclear translocation of the nuclear factor kappa B (NF-κB was observed by fluorescence microscope. Celastrol inhibited cell proliferation of LP-1 myeloma cell in a dose-dependent manner with IC50 values of 0.8817 µM, which was mediated through G1 cell cycle arrest and p27 induction. Celastrol induced apoptosis in LP-1 and RPMI 8226 myeloma cells in a time and dose dependent manner, and it involved Caspase-3 activation and NF-κB pathway. Celastrol down-modulated antiapoptotic proteins including Bcl-2 and survivin expression. The expression of NF-κB and IKKa were decreased after celastrol treatment. Celastrol effectively blocked the nuclear translocation of the p65 subunit and induced human multiple myeloma cell cycle arrest and apoptosis by p27 upregulation and NF-kB modulation. It has been demonstrated that the effect of celastrol on NF-kB was HO-1-independent by using zinc protoporphyrin-9 (ZnPPIX, a selective heme oxygenase inhibitor. From the results, it could be inferred that celastrol may be used as a NF-kB inhibitor to inhibit myeloma cell proliferation.

Physico Chemical Characteristic of Kappa Carrageenan Degraded Using Hydrogen Peroxide

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Rizky Febriansyah Siregar

2017-02-01

Full Text Available AbstractKappa carrageenan is polysaccharide that widely used in food, pharmaceutical, cosmetic, textile and printing industries as coagulate agent, stabilizer and gelling agent. Hydrogen peroxide (H2O2 is strong oxidator to degrade polysaccharide. Hydrogen peroxide has some advantades such as cheap, easy to get and savety environment. Degradation method using hydrogen peroxide is a technology based on establishment radical hydoxile reactive that attack the glycosidic of polysaccharides as a result reducing in molecular weight of polysaccharide. The aims of this study were to analyze the effect of hydrogen peroxide concentration, temperature and degradation time to molecular weight of refined kappa carrageenan. Structural changes on kappa carrageenan degradation were characterized by viscometer, SEM and FTIR. Hydrogen peroxide concentration, temperature and degradation time were significantly reducing molecular weight and changes in the structural function of refined kappa carrageenan. The lowest molecular weight of refined kappa carrageenan degraded was obtained from the treatment 3% of hydrogen peroxide at temperature 80°C and degradation time for 4 hours.

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.

Study Of Calcium And Potassium Different Nature Strength Gel Kappa-Carrageenan

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Петро Васильович Гурський

2015-07-01

Full Text Available The influence of certain organic and mineral salts of potassium and calcium for strength gel kappa-carrageenan. The influence of the mass concentration of individual calcium for strength gels with different content kappa-carrageenan. Grounded mass concentration of some calcium salts for use in the composition of the jelly for sweet and savory dishes based on kappa-carrageenan

Surface sensitivity of nuclear-knock-out form factors

International Nuclear Information System (INIS)

Fratamico, G.

1984-01-01

A numerical calculation has been performed to investigate the sensitivity of nuclear-knock-out form factors to nuclear-surface behaviour of bound-state wave functions. The result of our investigation suggests that one can extract the bound-state behaviour at the surface from experimental information on nuclear-knock-out form factors

Human factors in nuclear power plant operations

International Nuclear Information System (INIS)

Swain, A.D.

1980-08-01

This report describes some of the human factors problems in nuclear power plants and the technology that can be employed to reduce those problems. Many of the changes to improve the human factors in existing plants are inexpensive, and the expected gain in human reliability is substantial. The human factors technology is well-established and there are practitioners in most countries that have nuclear power plants

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

Ganoderma lucidum suppresses growth of breast cancer cells through the inhibition of Akt/NF-kappaB signaling.

Science.gov (United States)

Jiang, Jiahua; Slivova, Veronika; Harvey, Kevin; Valachovicova, Tatiana; Sliva, Daniel

2004-01-01

Ganoderma lucidum (Reishi, Lingzhi) is a popular Asian mushroom that has been used for more than 2 millennia for the general promotion of health and was therefore called the "Mushroom of Immortality." Ganoderma lucidum was also used in traditional Chinese medicine to prevent or treat a variety of diseases, including cancer. We previously demonstrated that Ganoderma lucidum suppresses the invasive behavior of breast cancer cells by inhibiting the transcription factor NF-kappaB. However, the molecular mechanisms responsible for the inhibitory effects of Ganoderma lucidum on the growth of highly invasive and metastatic breast cancer cells has not been fully elucidated. Here, we show that Ganoderma lucidum inhibits proliferation of breast cancer MDA-MB-231 cells by downregulating Akt/NF-kappaB signaling. Ganoderma lucidum suppresses phosphorylation of Akt on Ser473 and downregulates the expression of Akt, which results in the inhibition of NF-kappaB activity in MDA-MB-231 cells. The biological effect of Ganoderma lucidum was demonstrated by cell cycle arrest at G0/G1, which was the result of the downregulation of expression of NF-kappaB-regulated cyclin D1, followed by the inhibition of cdk4. Our results suggest that Ganoderma lucidum inhibits the growth of MDA-MB-231 breast cancer cells by modulating Akt/NF-kappaB signaling and could have potential therapeutic use for the treatment of breast cancer.

Improvement of Pulping Uniformity by Measurement of Single Fiber Kappa Number

Energy Technology Data Exchange (ETDEWEB)

Richard R. Gustafson; James B. Callis

2001-11-20

A method to measure the kappa of single fibers by staining with a fluorescent dye, Acridine Orange (AO), has been developed. This method is now applied to develop and automated flow-through instrument that permits routine kappa analysis on thousands of images of AO stained fibers to give the fiber kappa number distribution of a pulp sample in a few minutes. The design and operation of the instrument are similar to that of a flow cytometer but with the addition of extensive fiber imaging capability. Fluorescence measurements in the flow-through instrument are found to be consistent with those made with fluorescence microscope provided the signal processing in the flow-thou instrument is handled propertly. The kappa distributions of pulps that were analyzed by means of a density gradient column are compared to those measured with the flow-through instrument with good results. The kappa distributions of various laboratory pulps and commercial pulps have been measured. It has been found that all pulps are non-uniform but that ommercial pulps generally have broader kappa distributions thatn their laboratory counterparts. The effects of different pulping methods and chip pretreatments on pulp uniformity are discussed in the report. Finally, the application of flow-through fluorescence technology to other single fiber measurements are presented.

Human factors in nuclear power plants

International Nuclear Information System (INIS)

Pack, R.W.

1978-01-01

The Electric Power Research Institute has started research in human factors in nuclear power plants. One project, completed in March 1977, reviewed human factors problems in operating power plants and produced a report evaluating those problems. A second project developed computer programs for evaluating operator performance on training simulators. A third project is developing and evaluating control-room design approaches. A fourth project is reviewing human factors problems associated with power-plant maintainability and instrumentation and control technician activities. Human factors engineering is an interdisciplinary specialty concerned with influencing the design of equipment systems, facilities, and operational environments to promote safe, efficient, and reliable operator performance. The Electric Power Research Institute (EPRI) has undertaken four projects studying the application of human factors engineering principles to nuclear power plants. (author)

Cytokine regulation of pro- and anti-apoptotic genes in rat hepatocytes: NF-kappaB-regulated inhibitor of apoptosis protein 2 (cIAP2) prevents apoptosis

NARCIS (Netherlands)

Schoemaker, Marieke H.; Ros, Jenny E.; Homan, Manon; Trautwein, Christian; Liston, Peter; Poelstra, Klaas; van Goor, Harry; Jansen, Peter L. M.; Moshage, Han

2002-01-01

BACKGROUND/AIMS: In acute liver failure, hepatocytes are exposed to various cytokines that activate both cell survival and apoptotic pathways. NF-kappaB is a central transcription factor in these responses. Recent studies indicate that blocking NF-kappaB causes apoptosis, indicating the existence of

An aqueous stem bark extract of Mangifera indica (Vimang) inhibits T cell proliferation and TNF-induced activation of nuclear transcription factor NF-kappaB.

Science.gov (United States)

Garrido, Gabino; Blanco-Molina, Magdalena; Sancho, Rocío; Macho, Antonio; Delgado, René; Muñoz, Eduardo

2005-03-01

A commercial aqueous stem bark extract of Mangifera indica L. (Vimang) has been reported to have antiinflammatory, immunomodulatory and antioxidant activities. The molecular basis for these diverse properties is still unknown. This study shows that a stem bark extract of M. indica inhibits early and late events in T cell activation, including CD25 cell surface expression, progression to the S-phase of the cell cycle and proliferation in response to T cell receptor (TCR) stimulation. Moreover, the extract prevented TNFalpha-induced IkappaBalpha degradation and the binding of NF-kappaB to the DNA. This study may help to explain at the molecular level some of the biological activities attributed to the aqueous stem bark extract of M. indica (Vimang).

Characterization of immunoglobulin A kappa autoantibodies to human lactate dehydrogenase isoenzyme-3

NARCIS (Netherlands)

Weijers, R. N.; Oude Elferink, R. P.; Mulder, J.; Kruijswijk, H.

1987-01-01

We have purified with a cumulative recovery of 48% from the serum of a patient the immunoglobulin A kappa subunit of the lactate dehydrogenase-immunoglobulin A kappa (LD-IgA kappa) complex. It appears that the pI range of the complex is 5.4-5.8. The Ig part of the complex showed a monoclonal

Diclofenac inhibits tumor necrosis factor-α-induced nuclear factor-κB activation causing synergistic hepatocyte apoptosis.

Science.gov (United States)

Fredriksson, Lisa; Herpers, Bram; Benedetti, Giulia; Matadin, Quraisha; Puigvert, Jordi C; de Bont, Hans; Dragovic, Sanja; Vermeulen, Nico P E; Commandeur, Jan N M; Danen, Erik; de Graauw, Marjo; van de Water, Bob

2011-06-01

Drug-induced liver injury (DILI) is an important clinical problem. It involves crosstalk between drug toxicity and the immune system, but the exact mechanism at the cellular hepatocyte level is not well understood. Here we studied the mechanism of crosstalk in hepatocyte apoptosis caused by diclofenac and the proinflammatory cytokine tumor necrosis factor α (TNF-α). HepG2 cells were treated with diclofenac followed by TNF-α challenge and subsequent evaluation of necrosis and apoptosis. Diclofenac caused a mild apoptosis of HepG2 cells, which was strongly potentiated by TNF-α. A focused apoptosis machinery short interference RNA (siRNA) library screen identified that this TNF-α-mediated enhancement involved activation of caspase-3 through a caspase-8/Bid/APAF1 pathway. Diclofenac itself induced sustained activation of c-Jun N-terminal kinase (JNK) and inhibition of JNK decreased both diclofenac and diclofenac/TNF-α-induced apoptosis. Live cell imaging of GFPp65/RelA showed that diclofenac dampened the TNF-α-mediated nuclear factor kappaB (NF-κB) translocation oscillation in association with reduced NF-κB transcriptional activity. This was associated with inhibition by diclofenac of the TNF-α-induced phosphorylation of the inhibitor of NF-κB alpha (IκBα). Finally, inhibition of IκB kinase β (IKKβ) with BMS-345541 as well as stable lentiviral short hairpin RNA (shRNA)-based knockdown of p65/RelA sensitized hepatocytes towards diclofenac/TNF-α-induced cytotoxicity. Together, our data suggest a model whereby diclofenac-mediated stress signaling suppresses TNF-α-induced survival signaling routes and sensitizes cells to apoptosis. Copyright © 2011 American Association for the Study of Liver Diseases.

Ion and electron Kappa distribution functions in the plasma sheet.

Science.gov (United States)

Moya, P. S.; Stepanova, M. V.; Espinoza, C.; Antonova, E. E.; Valdivia, J. A.

2017-12-01

We present a study of ion and electron flux spectra in the Earth's plasma sheet using kappa distribution functions. Satellite data from the THEMIS mission were collected for thousands of crossings through the plasma sheet, between 7 and 35 Re and during the years 2008-2009. The events were separated according to the geomagnetic activity at the time. Our results show the distribution of the kappa index and characteristic energies across the plasma sheet and its evolution with distance to Earth for quiet times and for the substorm expansion and recovery phases. For the ions, it is observed that the kappa values tend to decrease outwards and that this effect is more significant in the dusk sector, where the smallest values are found for distances beyond 15 Re. The main effect of the substorms appears as an enhancement of this behavior. The electrons show a much more homogeneous distribution in quiet times, with a mild tendency for larger kappa values at larger distances. During substorms, the kappa values tend to equalize and appear very homogenous during expansion. However, they exhibit a significant increase in the dusk sector during the recovery substorm phase. Finally, we observe that the characteristic energy of the particles during substorms increases and concentrate at distances less than 15 Re.

Importance of human factors on nuclear installations safety

International Nuclear Information System (INIS)

Caruso, G.J.

1990-01-01

Actually, installations safety and, in particular the nuclear installations infer a strong incidence in human factors related to the design and operation of such installations. In general, the experience aims to that the most important accidents have happened as result of the components' failures combination and human failures in the operation of safety systems. Human factors in the nuclear installations may be divided into two areas: economy and human reliability. Human factors treatments for the safety evaluation of the nuclear installations allow to diagnose the weak points of man-machine interaction. (Author) [es

Kappa statistic to measure agreement beyond chance in free-response assessments.

Science.gov (United States)

Carpentier, Marc; Combescure, Christophe; Merlini, Laura; Perneger, Thomas V

2017-04-19

The usual kappa statistic requires that all observations be enumerated. However, in free-response assessments, only positive (or abnormal) findings are notified, but negative (or normal) findings are not. This situation occurs frequently in imaging or other diagnostic studies. We propose here a kappa statistic that is suitable for free-response assessments. We derived the equivalent of Cohen's kappa statistic for two raters under the assumption that the number of possible findings for any given patient is very large, as well as a formula for sampling variance that is applicable to independent observations (for clustered observations, a bootstrap procedure is proposed). The proposed statistic was applied to a real-life dataset, and compared with the common practice of collapsing observations within a finite number of regions of interest. The free-response kappa is computed from the total numbers of discordant (b and c) and concordant positive (d) observations made in all patients, as 2d/(b + c + 2d). In 84 full-body magnetic resonance imaging procedures in children that were evaluated by 2 independent raters, the free-response kappa statistic was 0.820. Aggregation of results within regions of interest resulted in overestimation of agreement beyond chance. The free-response kappa provides an estimate of agreement beyond chance in situations where only positive findings are reported by raters.

Effect of lifestyle interventions with or without metformin therapy on serum levels of osteoprotegerin and receptor activator of nuclear factor kappa B ligand in patients with prediabetes.

Science.gov (United States)

Arslan, Muyesser Sayki; Tutal, Esra; Sahin, Mustafa; Karakose, Melia; Ucan, Bekir; Ozturk, Gulfer; Cakal, Erman; Biyikli Gencturk, Zeynep; Ozbek, Mustafa; Delibasi, Tuncay

2017-02-01

Osteoprotegerin has been shown to be increased in cardiovascular disorders and type 2 diabetes mellitus. Prediabetes represents a high risk condition for diabetes and diabetic complications. Therefore, we aimed to find the relationship between prediabetes and osteoprotegerin with nuclear factor-B ligand, carotid intima media thickness, and metabolic markers. A total of 54 participants with prediabetes including impaired fasting glucose (n = 21), impaired glucose tolerance (n = 8), impaired fasting glucose and impaired glucose tolerance (n = 25), and 60 healthy individuals as a control were admitted to the study. Metabolic and anthropometric parameters, insulin resistance variables, osteoprotegerin, and nuclear factor-B ligand markers, carotid intima media thickness were examined at baseline for all participants. To evaluate the effect of therapy we determined the same parameters after the end of the study. Measurements of waist circumference, body mass index, body fat percentage and levels of fasting blood glucose, fasting insulin, homeostatic model assessment of insulin resistance, triglyceride levels and hsCRP and carotid intima media thickness were significantly higher in patients with prediabetes (p  0.05). Patients with prediabetes were under lifestyle interventions with (group 1, n = 33) or without metformin (group 2, n = 21) therapy. Baseline anthropometric and metabolic characteristics were not found statistically different in group 1 and group 2. Mean follow up period of the patients were 7.9 ± 2.2 month (min-max: 6-12 months). After the follow up period we evaluated the same parameters and found significant differences between waist circumference, body mass index, body fat percentage, fasting insulin, homeostatic model assessment of insulin resistance, and osteoprotegerin levels (p prediabetes was associated with a significant decrease in osteoprotegerin and certain metabolic variables together with an increase in nuclear

PENGARUH KONSUMSI KAPPA-KARAGENAN TERHADAP GLUKOSA DARAH TIKUS WISTAR (Ratus norvegicus DIABETES [The Effect of Kappa-Carrageenan Consumption on Blood Glucose Level of Diabetic Wistar Rat (Ratus norwegicus

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Hardoko

2006-04-01

Full Text Available The effect of kappa-carrageenan consumption on blood glucose level were studied on diabetic male wistar rat (Ratus norvegicus.The rats were made diabetic by aloxan injection, and then were given that a ration contains 5, 10, 15, 20% (w/w kappa-carrageenan, standard ration (negative control, and parental glibenklamid (positive control. The results showed that the standard ration could not reduce blood glucose from hyperglycemic to normal level, while the ration contained kappacarrageenan could. The higher kappa-carrageenan seaweed level in the ration has higher capacity to decrease blood glucose level. The ration containing 20% and 15% kappa-carrageenan could reduce blood glucose in 18 and 21 days, respectively.The effect of this ration was similar to that of glibenklamid which reduced blood glucose to normal level in 18 days. The ration containing 5 and 10% kappa-carrageenan could reduce blood glucose level; Blood glucose leve return to normal on the 21st day.

Nomogram for sample size calculation on a straightforward basis for the kappa statistic.

Science.gov (United States)

Hong, Hyunsook; Choi, Yunhee; Hahn, Seokyung; Park, Sue Kyung; Park, Byung-Joo

2014-09-01

Kappa is a widely used measure of agreement. However, it may not be straightforward in some situation such as sample size calculation due to the kappa paradox: high agreement but low kappa. Hence, it seems reasonable in sample size calculation that the level of agreement under a certain marginal prevalence is considered in terms of a simple proportion of agreement rather than a kappa value. Therefore, sample size formulae and nomograms using a simple proportion of agreement rather than a kappa under certain marginal prevalences are proposed. A sample size formula was derived using the kappa statistic under the common correlation model and goodness-of-fit statistic. The nomogram for the sample size formula was developed using SAS 9.3. The sample size formulae using a simple proportion of agreement instead of a kappa statistic and nomograms to eliminate the inconvenience of using a mathematical formula were produced. A nomogram for sample size calculation with a simple proportion of agreement should be useful in the planning stages when the focus of interest is on testing the hypothesis of interobserver agreement involving two raters and nominal outcome measures. Copyright © 2014 Elsevier Inc. All rights reserved.

Human factor problem in nuclear power generation

International Nuclear Information System (INIS)

Yoshino, Kenji; Fujimoto, Junzo

1999-01-01

Since a nuclear power plant accident at Threemile Island in U.S.A. occurred in March, 1979, twenty years have passed. After the accident, the human factor problem became focussed in nuclear power, to succeed its research at present. For direct reason of human error, most of factors at individual level or work operation level are often listed at their center. Then, it is natural that studies on design of a machine or apparatus suitable for various human functions and abilities and on improvement of relationship between 'human being and machine' and 'human being and working environment' are important in future. Here was, as first, described on outlines of the human factor problem in a nuclear power plant developed at a chance of past important accident, and then was described on educational training for its countermeasure. At last, some concrete researching results obtained by human factor research were introduced. (G.K.)

Low nuclear body formation and tax SUMOylation do not prevent NF-kappaB promoter activation

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Bonnet Amandine

2012-09-01

Full Text Available Abstract Background The Tax protein encoded by Human T-lymphotropic virus type 1 (HTLV-1 is a powerful activator of the NF-κB pathway, a property critical for HTLV-1-induced immortalization of CD4+ T lymphocytes. Tax permanently stimulates this pathway at a cytoplasmic level by activating the IκB kinase (IKK complex and at a nuclear level by enhancing the binding of the NF-κB factor RelA to its cognate promoters and by forming nuclear bodies, believed to represent transcriptionally active structures. In previous studies, we reported that Tax ubiquitination and SUMOylation play a critical role in Tax localization and NF-κB activation. Indeed, analysis of lysine Tax mutants fused or not to ubiquitin or SUMO led us to propose a two-step model in which Tax ubiquitination first intervenes to activate IKK while Tax SUMOylation is subsequently required for promoter activation within Tax nuclear bodies. However, recent studies showing that ubiquitin or SUMO can modulate Tax activities in either the nucleus or the cytoplasm and that SUMOylated Tax can serve as substrate for ubiquitination suggested that Tax ubiquitination and SUMOylation may mediate redundant rather than successive functions. Results In this study, we analyzed the properties of a new Tax mutant that is properly ubiquitinated, but defective for both nuclear body formation and SUMOylation. We report that reducing Tax SUMOylation and nuclear body formation do not alter the ability of Tax to activate IKK, induce RelA nuclear translocation, and trigger gene expression from a NF-κB promoter. Importantly, potent NF-κB promoter activation by Tax despite low SUMOylation and nuclear body formation is also observed in T cells, including CD4+ primary T lymphocytes. Moreover, we show that Tax nuclear bodies are hardly observed in HTLV-1-infected T cells. Finally, we provide direct evidence that the degree of NF-κB activation by Tax correlates with the level of Tax ubiquitination, but not

Low nuclear body formation and tax SUMOylation do not prevent NF-kappaB promoter activation.

Science.gov (United States)

Bonnet, Amandine; Randrianarison-Huetz, Voahangy; Nzounza, Patrycja; Nedelec, Martine; Chazal, Maxime; Waast, Laetitia; Pene, Sabrina; Bazarbachi, Ali; Mahieux, Renaud; Bénit, Laurence; Pique, Claudine

2012-09-25

The Tax protein encoded by Human T-lymphotropic virus type 1 (HTLV-1) is a powerful activator of the NF-κB pathway, a property critical for HTLV-1-induced immortalization of CD4⁺ T lymphocytes. Tax permanently stimulates this pathway at a cytoplasmic level by activating the IκB kinase (IKK) complex and at a nuclear level by enhancing the binding of the NF-κB factor RelA to its cognate promoters and by forming nuclear bodies, believed to represent transcriptionally active structures. In previous studies, we reported that Tax ubiquitination and SUMOylation play a critical role in Tax localization and NF-κB activation. Indeed, analysis of lysine Tax mutants fused or not to ubiquitin or SUMO led us to propose a two-step model in which Tax ubiquitination first intervenes to activate IKK while Tax SUMOylation is subsequently required for promoter activation within Tax nuclear bodies. However, recent studies showing that ubiquitin or SUMO can modulate Tax activities in either the nucleus or the cytoplasm and that SUMOylated Tax can serve as substrate for ubiquitination suggested that Tax ubiquitination and SUMOylation may mediate redundant rather than successive functions. In this study, we analyzed the properties of a new Tax mutant that is properly ubiquitinated, but defective for both nuclear body formation and SUMOylation. We report that reducing Tax SUMOylation and nuclear body formation do not alter the ability of Tax to activate IKK, induce RelA nuclear translocation, and trigger gene expression from a NF-κB promoter. Importantly, potent NF-κB promoter activation by Tax despite low SUMOylation and nuclear body formation is also observed in T cells, including CD4⁺ primary T lymphocytes. Moreover, we show that Tax nuclear bodies are hardly observed in HTLV-1-infected T cells. Finally, we provide direct evidence that the degree of NF-κB activation by Tax correlates with the level of Tax ubiquitination, but not SUMOylation. These data reveal that the

Kappa opioid receptors stimulate phosphoinositide turnover in rat brain

Energy Technology Data Exchange (ETDEWEB)

Periyasamy, S.; Hoss, W. (Univ. of Toledo, OH (USA))

1990-01-01

The effects of various subtype-selective opioid agonists and antagonists on the phosphoinositide (PI) turnover response were investigated in the rat brain. The {kappa}-agonists U-50,488H and ketocyclazocine produced a concentration-dependent increase in the accumulation of IP's in hippocampal slices. The other {kappa}-agonists Dynorphin-A (1-13) amide, and its protected analog D(Ala){sup 2}-dynorphin-A (1-13) amide also produced a significant increase in the formation of ({sup 3}H)-IP's, whereas the {mu}-selective agonists (D-Ala{sup 2}-N-Me-Phe{sup 4}-Gly{sup 5}-ol)-enkephalin and morphine and the {delta}-selective agonist (D-Pen{sup 2,5})-enkephalin were ineffective. The increase in IP's formation elicited by U-50,488H was partially antagonized by naloxone and more completely antagonized by the {kappa}-selective antagonists nor-binaltorphimine and MR 2266. The formation of IP's induced by U-50,488H varies with the regions of the brain used, being highest in hippocampus and amygdala, and lowest in striatum and pons-medullar. The results indicate that brain {kappa}- but neither {mu}- nor {delta}- receptors are coupled to the PI turnover response.

Distribution of kappa opioid receptors in the brain of young and old male rats

International Nuclear Information System (INIS)

Maggi, R.; Limonta, P.; Dondi, D.; Martini, L.; Piva, F.

1989-01-01

The experiments to be described have been designed in order to: (a) provide new information on the concentrations of opioid kappa receptors in different regions of the brain of the male rats; and (b) to analyze whether the density of brain kappa receptors might be modified by the process of aging. The concentration of kappa receptors was investigated in the hypothalamus, amygdala, mesencephalon, corpus striatum, hippocampus, thalamus, frontal poles, anterior and posterior cortex collected from male rats of 2 and 19 months of age. 3 H-bremazocine (BRZ) was used as the ligand of kappa receptors, after protection of mu and delta receptors respectively with dihydromorphine and d-ala-d-leu-enkephalin. The results obtained show that: (1) in young male rats, the number of kappa opioid receptors is different in the various brain areas examined. (2) Aging exerts little influence on the number of kappa receptors in the majority of the brain structures considered. However in the amygdala and in the thalamus the number of kappa receptors was increased in old animals

Human factors in nuclear safety oversight

International Nuclear Information System (INIS)

Taylor, K.

1989-01-01

The mission of the nuclear safety oversight function at the Savannah River Plant is to enhance the process and nuclear safety of site facilities. One of the major goals surrounding this mission is the reduction of human error. It is for this reason that several human factors engineers are assigned to the Operations assessment Group of the Facility Safety Evaluation Section (FSES). The initial task of the human factors contingent was the design and implementation of a site wide root cause analysis program. The intent of this system is to determine the most prevalent sources of human error in facility operations and to assist in determining where the limited human factors resources should be focused. In this paper the strategy used to educate the organization about the field of human factors is described. Creating an awareness of the importance of human factors engineering in all facets of design, operation, and maintenance is considered to be an important step in reducing the rate of human error

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...

Effects of protein-energy malnutrition on NF-kappaB signalling in murine peritoneal macrophages.

Science.gov (United States)

Fock, Ricardo Ambrósio; Rogero, Marcelo Macedo; Vinolo, Marco Aurélio Ramirez; Curi, Rui; Borges, Maria Carolina; Borelli, Primavera

2010-04-01

Protein-energy malnutrition (PEM) is an important public health problem affecting millions of people worldwide. PEM decreases resistance to infection, impairing a number of physiological processes. In unstimulated cells, NF-kappaB is kept from binding to its consensus sequence by the inhibitor I kappaB alpha, which retains NF-kappaB in the cytoplasm. Upon various signals, such as lipopolysaccharide (LPS), I kappaB alpha is rapidly degraded and NF-kappaB is induced to translocate into the nucleus, where it activates expression of various genes that participate in the inflammatory response, including those involved in the synthesis of TNF-alpha. TRAF-6 is a cytoplasmic adapter protein that links the stimulatory signal from Toll like receptor-4 to NF-kappaB. The aim of this study was to evaluate the effect of malnutrition on induction of TNF-alpha by LPS in murine peritoneal macrophages. We evaluated peritoneal cellularity, the expression of MyD88, TRAF-6, IKK, I kappaB alpha and NF-kappaB, NF-kappaB activation and TNF-alpha mRNA and protein synthesis in macrophages. Two-month-old male BALB/C mice were submitted to PEM with a low-protein diet that contained 2% protein, compared to 12% protein in the control diet. When the experimental group had lost about 20% of the original body weight, it was used in the subsequent experiments. Malnourished animals presented anemia, leucopenia and severe reduction in peritoneal cavity cellularity. TNF-alpha mRNA and protein levels of macrophages stimulated with LPS were significantly lower in malnourished animals. PEM also decreased TRAF-6 expression and NF-kappaB activation after LPS stimulation. These results led us to conclude that PEM changes NF-kB signalling pathway in macrophages to LPS stimulus.

Human Factor on Gravelines Nuclear Power Plants

International Nuclear Information System (INIS)

Duboc, Gerard

1998-01-01

In a first part, the documents describes the commitments by EDF nuclear power plan operations to demands made by the Safety Authority regarding actions in the field of human factors (concerns expressed by the Authority, in-depth analysis, positions on different points raised by the Authority). In a second part, it presents the various actions undertaken in the Gravelines nuclear power station regarding human factors: creation of an 'operator club' (mission and objectives, methods and means, first meetings, tracking file), development of risk analysis strategy, setting up of a human factor engineering mission and example of action in case of a significant event

Vanillin improves and prevents trinitrobenzene sulfonic acid-induced colitis in mice.

Science.gov (United States)

Wu, Shih-Lu; Chen, Jaw-Chyun; Li, Chia-Cheng; Lo, Hsin-Yi; Ho, Tin-Yun; Hsiang, Chien-Yun

2009-08-01

Inflammatory bowel disease (IBD) is chronic inflammatory and relapsing disease of the gut. It has been known that activation of nuclear factor-kappaB (NF-kappaB) and production of proinflammatory cytokines play important roles in the pathogenesis of IBD. In this study, the effect of vanillin (4-hydroxy-3-methoxybenzaldehyde), a potent nuclear factor-kappaB (NF-kappaB) inhibitor, was evaluated in mice with trinitrobenzene sulfonic acid (TNBS)-induced colitis. Oral administration of vanillin improved macroscopic and histological features of TNBS-induced colitis in a dose-dependent manner. Vanillin not only prevented TNBS-induced colitis but also ameliorated the established colitis. By in vivo NF-kappaB bioluminescence imaging, electrophoretic mobility shift assay, and Western blot, we found that vanillin suppressed in vivo NF-kappaB activities through the inhibition of p65 translocation, inhibitor of nuclear factor-kappaB(IkappaB)-alpha phosphorylation, and IkappaB kinase activation. Furthermore, vanillin reduced the expressions of proinflammatory cytokines [interleukin (IL)-1beta, IL-6, interferon-gamma, and tumor necrosis factor-alpha] and stimulated the expression of anti-inflammatory cytokine (IL-4) in colonic tissues. In conclusion, this work identified vanillin as an anti-inflammatory compound with the capacity to prevent and ameliorate TNBS-induced colitis. Due to its safety, vanillin could be a potent candidate for the treatment of IBD.

Nuclear safety regulation on nuclear safety equipment activities in relation to human and organizational factors

International Nuclear Information System (INIS)

Li Tianshu

2013-01-01

Based on years of knowledge in nuclear safety supervision and experience of investigating and dealing with violation events in repair welding of DFHM, this paper analyzes major faults in manufacturing and maintaining activities of nuclear safety equipment in relation to human and organizational factors. It could be deducted that human and organizational factors has definitely become key features in the development of nuclear energy and technology. Some feasible measures to reinforce supervision on nuclear safety equipment activities have also been proposed. (author)

The significance of human factors in nuclear activities

International Nuclear Information System (INIS)

Weil, L.; Berg, H.P.

1999-01-01

Human factors is an aspect increasingly investigated in the last few years in efforts and programmes for enhancing the operational safety of nuclear systems. Methodology has been elaborated for analysis and evaluation of human reliability, or development of instruments supporting the decisions to be taken by the operators at the man-control room interface of nuclear installations, as well as initial approaches to introduce organisational factors which may influence the man-machine function allocation, and thus are an element of the safety culture concept. The significance of human factors in nuclear activities, as well as activities at the national and international level for optimisation of the man-machine interface and the man-organisation interface are discussed. (orig./CB) [de

Effect of particle size on hydroxyapatite crystal-induced tumor necrosis factor alpha secretion by macrophages.

Science.gov (United States)

Nadra, Imad; Boccaccini, Aldo R; Philippidis, Pandelis; Whelan, Linda C; McCarthy, Geraldine M; Haskard, Dorian O; Landis, R Clive

2008-01-01

Macrophages may promote a vicious cycle of inflammation and calcification in the vessel wall by ingesting neointimal calcific deposits (predominantly hydroxyapatite) and secreting tumor necrosis factor (TNF)alpha, itself a vascular calcifying agent. Here we have investigated whether particle size affects the proinflammatory potential of hydroxyapatite crystals in vitro and whether the nuclear factor (NF)-kappaB pathway plays a role in the macrophage TNFalpha response. The particle size and nano-topography of nine different crystal preparations was analyzed by X-ray diffraction, Raman spectroscopy, scanning electron microscopy and gas sorbtion analysis. Macrophage TNFalpha secretion was inversely related to hydroxyapatite particle size (P=0.011, Spearman rank correlation test) and surface pore size (P=0.014). A necessary role for the NF-kappaB pathway was demonstrated by time-dependent I kappaB alpha degradation and sensitivity to inhibitors of I kappaB alpha degradation. To test whether smaller particles were intrinsically more bioactive, their mitogenic activity on fibroblast proliferation was examined. This showed close correlation between TNFalpha secretion and crystal-induced fibroblast proliferation (P=0.007). In conclusion, the ability of hydroxyapatite crystals to stimulate macrophage TNFalpha secretion depends on NF-kappaB activation and is inversely related to particle and pore size, with crystals of 1-2 microm diameter and pore size of 10-50 A the most bioactive. Microscopic calcific deposits in early stages of atherosclerosis may therefore pose a greater inflammatory risk to the plaque than macroscopically or radiologically visible deposits in more advanced lesions.

Human factors in nuclear power plants

International Nuclear Information System (INIS)

Hennig, J.; Bohr, E.

1976-04-01

This annotated bibliography is a first attempt to give a survey of the kind of literature which is relevant for the ergonomic working conditions in nuclear power plants. Such a survey seems to be useful in view of the fact that the 'factor human being' comes recently more and more to the fore in nuclear power plants. In this context, the necessity is often pointed out to systematically include our knowledge of the performance capacity and limits of human beings when designing the working conditions for the personnel of nuclear power plants. For this reason, the bibliography is so much intended for the ergonomics experts as for the experts of nuclear engineering. (orig./LN) [de

Immunoglobulin gene expression and regulation of rearrangement in kappa transgenic mice

International Nuclear Information System (INIS)

Ritchie, K.A.

1986-01-01

Transgenic mice were produced by microinjection of the functionally rearranged immunoglobulin kappa gene from the myeloma MOPC-21 into the male pronucleus of fertilized mouse eggs, and implantation of the microinjected embryos into foster mothers. Mice that integrated the injected gene were detected by hybridizing tail DNA dots with radioactively labelled pBR322 plasmid DNA, which detects pBR322 sequences left as a tag on the microinjected DNA. Mice that integrated the injected gene (six males) were mated and the DNA, RNA and serum kappa chains of their offspring were analyzed. A rabbit anti-mouse kappa chain antiserum was also produced for use in detection of mouse kappa chains on protein blots. Hybridomas were produced from the spleen cells of these kappa transgenic mice to immortalize representative B cells and to investigate expression of the transgenic kappa gene, its effect on allelic exclusion, and its effect on the control of light chain gene rearrangement and expression. The results show that the microinjected DNA is integrated as concatamers in unique single or, rarely, two separate sites in the genome. The concatamers are composed of several copies (16 to 64) of injected DNA arranged in a head to tail fashion. The transgene is expressed into protein normally and in a tissue specific fashion. For the first time in these transgenic mice, all tissues contain a functionally rearranged and potentially expressible immunoglobulin gene. The transgene is expressed only in B cells and not in hepatocytes, for example. This indicates that rearrangement of immunoglobulin genes is necessary but not sufficient for the tissue specific expression of these genes by B cells

The human factor in the nuclear industry

International Nuclear Information System (INIS)

Colas, Armand

1998-01-01

After having evoked the progressive reduction and stabilization of significant incidents occurring every year in French nuclear power plants, and the challenges faced by nuclear energy (loss of public confidence, loss of competitiveness), and then outlined the importance of safety to overcome these challenges, the author comments EDF's approach to the human factor. He first highlights the importance of information and communication towards the population. He briefly discusses the meaning of human factors for the nuclear industry, sometimes perceived as the contribution people to the company's safety and performance. He comments the evolution observed in the perception of human error in different industrial or technical environments and situations, and outlines what is at stake to reduce the production of faults and organize a 'hunt for latent defects'

Factor of radioactive waste on nuclear power program

International Nuclear Information System (INIS)

Syed Abdul Malik Syed Zain

2009-01-01

Global warming phenomena and rising oil prices have brought the excitement of open space use of nuclear power. Arguments in favor of this technology range in terms of more environmentally friendly, energy diversification and cost efficiency has prompted the government to widen the choice of nuclear power be considered as a serious alternative. Despite the attractive factors to the use of these powers, there are also factors that stem from the continued development of nuclear power. These include the factor of safety, security, security of fuel supply, and public attention is often associated with radioactive waste management. This article attempts to debate specific to radioactive waste management factors that impact on public acceptance of a country's nuclear power program, especially in Malaysia. Starting from the absence of radioactive waste management policy to model uncertainty of the landfill and complications in selecting a repository site shows the basic infrastructure is still lacking. In addition, previous experience handling thorium waste has not reached a final settlement after several years of implementation. It reinforced the perception about the level of public confidence in the competence and attitude of local workers who are not very encouraging to pursue this advanced.

Receptor tyrosine phosphatase R-PTP-kappa mediates homophilic binding

DEFF Research Database (Denmark)

Sap, J; Jiang, Y P; Friedlander, D

1994-01-01

Receptor tyrosine phosphatases (R-PTPases) feature PTPase domains in the context of a receptor-like transmembrane topology. The R-PTPase R-PTP-kappa displays an extracellular domain composed of fibronectin type III motifs, a single immunoglobulin domain, as well as a recently defined MAM domain (Y...... not require PTPase activity or posttranslational proteolytic cleavage of the R-PTP-kappa protein and is calcium independent. The results suggest that R-PTPases may provide a link between cell-cell contact and cellular signaling events involving tyrosine phosphorylation....

Factors influencing chemical durability of nuclear waste glasses

International Nuclear Information System (INIS)

Feng, Xiangdong; Bates, J.K.

1993-01-01

A short summary is given of our studies on the major factors that affect the chemical durability of nuclear waste glasses. These factors include glass composition, solution composition, SA/V (ratio of glass surface area to the volume of solution), radiation, and colloidal formation. These investigations have enabled us to gain a better understanding of the chemical durability of nuclear waste glasses and to accumulate.a data base for modeling the long-term durability of waste glass, which will be used in the risk assessment of nuclear waste disposal. This knowledge gained also enhances our ability to formulate optimal waste glass compositions

Short communication: molecular characterization of dog and cat p65 subunits of NF-kappaB.

Science.gov (United States)

Ishikawa, Shingo; Takemitsu, Hiroshi; Li, Gebin; Mori, Nobuko; Yamamoto, Ichiro; Arai, Toshiro

2015-04-01

Nuclear factor kappa B (NF-κB) plays an important role in the immune system. The p65 subunit is an important part of NF-κB unit, and studies of dog and cat p65 subunits of NF-κB (dp65 and cp65) are important in understanding their immune function. In this study, we described the molecular characterization of dp65 and cp65. The dp65 and cp65 complementary DNA encoded 542 and 555 amino acids, respectively, showing a high sequence homology with the mammalian p65 subunit (>87.5%). Quantitative polymerase chain reaction revealed that the p65 messenger RNA is highly expressed in the dog stomach and cat heart and adipose tissue. Functional NF-κB promoter-luciferase reporter vectors revealed that our isolated dp65 and cp65 cDNA encodes a functionally active protein. Transiently expressed dp65 and cp65 up-regulated pro-inflammatory cytokine expression levels in dog and cat, respectively. These findings suggest that dp65 and cp65 play important roles in regulating immune function. Copyright © 2015 Elsevier Ltd. All rights reserved.

Acrolein inhibits cytokine gene expression by alkylating cysteine and arginine residues in the NF-kappaB1 DNA binding domain.

Science.gov (United States)

Lambert, Cherie; Li, Jimei; Jonscher, Karen; Yang, Teng-Chieh; Reigan, Philip; Quintana, Megan; Harvey, Jean; Freed, Brian M

2007-07-06

Cigarette smoke is a potent inhibitor of pulmonary T cell responses, resulting in decreased immune surveillance and an increased incidence of respiratory tract infections. The alpha,beta-unsaturated aldehydes in cigarette smoke (acrolein and crotonaldehyde) inhibited production of interleukin-2 (IL-2), IL-10, granulocyte-macrophage colony-stimulating factor, interferon-gamma, and tumor necrosis factor-alpha by human T cells but did not inhibit production of IL-8. The saturated aldehydes (acetaldehyde, propionaldehyde, and butyraldehyde) in cigarette smoke were inactive. Acrolein inhibited induction of NF-kappaB DNA binding activity after mitogenic stimulation of T cells but had no effect on induction of NFAT or AP-1. Acrolein inhibited NF-kappaB1 (p50) binding to the IL-2 promoter in a chromatin immunoprecipitation assay by >99%. Using purified recombinant p50 in an electrophoretic mobility shift assay, we demonstrated that acrolein was 2000-fold more potent than crotonaldehyde in blocking DNA binding to an NF-kappaB consensus sequence. Matrix-assisted laser desorption/ionization time-of-flight and tandem mass spectrometry demonstrated that acrolein alkylated two amino acids (Cys-61 and Arg-307) in the DNA binding domain. Crotonaldehyde reacted with Cys-61, but not Arg-307, whereas the saturated aldehydes in cigarette smoke did not react with p50. These experiments demonstrate that aldehydes in cigarette smoke can regulate gene expression by direct modification of a transcription factor.

Sex Differences in Kappa Opioid Receptor Function and Their Potential Impact on Addiction

OpenAIRE

Chartoff, Elena H.; Mavrikaki, Maria

2015-01-01

Behavioral, biological, and social sequelae that lead to drug addiction differ between men and women. Our efforts to understand addiction on a mechanistic level must include studies in both males and females. Stress, anxiety, and depression are tightly linked to addiction, and whether they precede or result from compulsive drug use depends on many factors, including biological sex. The neuropeptide dynorphin (DYN), an endogenous ligand at kappa opioid receptors (KORs), is necessary for stress...

Human and organizational factors in nuclear safety

International Nuclear Information System (INIS)

Garcia, A.; Barrientos, M.; Gil, B.

2015-01-01

Nuclear installations are socio technical systems where human and organizational factors, in both utilities and regulators, have a significant impact on safety. Three Mile Island (TMI) accident, original of several initiatives in the human factors field, nevertheless became a lost opportunity to timely acquire lessons related to the upper tiers of the system. Nowadays, Spanish nuclear installations have integrated in their processes specialists and activities in human and organizational factors, promoted by the licensees After many years of hard work, Spanish installations have achieved a better position to face new challenges, such as those posed by Fukushima. With this experience, only technology-centered action plan would not be acceptable, turning this accident in yet another lost opportunity. (Author)

Uranium, a factor limiting nuclear energy?

International Nuclear Information System (INIS)

Ohnemus, J.

2006-01-01

Nuclear power has been back as a topic of public debate since early this year. A special subject under discussion is the extension of nuclear power plant life. Hardly had it been on the agenda, when interested parties announced that this step was impossible because uranium reserves were no longer sufficient. A variety of terms are being used in this discussion without their meaning being taken into account: stocks, resources, and reserves. To clarify the situation, this article outlines important aspects of short and long term uranium supplies, and analyzes their meaning. Here are some of the most important issues under consideration: - For what period of time is there really enough uranium? - Is uranium becoming the limiting factor in the use of nuclear power? - Is uranium really a 'sustainable' energy resource? - Will higher prices extend the range? - What is the influence of the price of uranium on the cost of electricity generation? Among other results, it is found that comprehensive sources of low-price uranium and nuclear fuels are, or can be made, available worldwide. Consequently, the 'range' is beyond the time frames currently mentioned, also as a function of technological factors, i.e. reaching several hundred years. It is also important to note that nuclear power - ensures greater independence of volatile imported sources, - guarantees reliably low electricity prices, - has a huge potential of environmental protection, and - is a clean source of energy. (orig.)

Uranium, a factor limiting nuclear energy?

International Nuclear Information System (INIS)

2006-01-01

Nuclear power has been back as a topic of public debate since early this year. A special subject under discussion is the extension of nuclear power plant life. Hardly had it been on the agenda, when interested parties announced that this step was impossible because uranium reserves were no longer sufficient. A variety of terms are being used in this discussion without their meaning being taken into account: stocks, resources, and reserves. To clarify the situation, this article outlines important aspects of short and long term uranium supplies, and analyzes their meaning. Here are some of the most important issues under consideration: - For what period of time is there really enough uranium? - Is uranium becoming the limiting factor in the use of nuclear power? - Is uranium really a 'sustainable' energy resource? - Will higher prices extend the range? - What is the influence of the price of uranium on the cost of electricity generation? Among other results, it is found that comprehensive sources of low-price uranium and nuclear fuels are, or can be made, available worldwide. Consequently, the 'range' is beyond the time frames currently mentioned, also as a function of technological factors, i.e. reaching several hundred years. It is also important to note that nuclear power - ensures greater independence of volatile imported sources, - guarantees reliably low electricity prices, - has a huge potential of environmental protection, and - is a clean source of energy. (orig./GL)

Development of human factors engineering guide for nuclear power project

International Nuclear Information System (INIS)

Wu Dangshi; Sheng Jufang

1997-01-01

'THE PRACTICAL GUIDE FOR APPLICATION OF HUMAN FACTORS ENGINEERING TO NUCLEAR POWER PROJECT (First Draft, in Chinese)', which was developed under a research program sponsored by National Nuclear Safety Administration (NNSA) is described briefly. It is hoped that more conscious, more systematical and more comprehensive application of Human Factors Engineering to the nuclear power projects from the preliminary feasibility studies up to the commercial operation will benefit the safe, efficient and economical operations of nuclear power plants in China

Involvement of nuclear factor κB in platelet CD40 signaling

International Nuclear Information System (INIS)

Hachem, Ahmed; Yacoub, Daniel; Zaid, Younes; Mourad, Walid; Merhi, Yahye

2012-01-01

Highlights: ► sCD40L induces TRAF2 association to CD40 and NF-κB activation in platelets. ► IκBα phosphorylation downstream of CD40L/CD40 signaling is independent of p38 MAPK phosphorylation. ► IκBα is required for sCD40L-induced platelet activation and potentiation of aggregation. -- Abstract: CD40 ligand (CD40L) is a thrombo-inflammatory molecule that predicts cardiovascular events. Platelets constitute the major source of soluble CD40L (sCD40L), which has been shown to potentiate platelet activation and aggregation, in a CD40-dependent manner, via p38 mitogen activated protein kinase (MAPK) and Rac1 signaling. In many cells, the CD40L/CD40 dyad also induces activation of nuclear factor kappa B (NF-κB). Given that platelets contain NF-κB, we hypothesized that it may be involved in platelet CD40 signaling and function. In human platelets, sCD40L induces association of CD40 with its adaptor protein the tumor necrosis factor receptor associated factor 2 and triggers phosphorylation of IκBα, which are abolished by CD40L blockade. Inhibition of IκBα phosphorylation reverses sCD40L-induced IκBα phosphorylation without affecting p38 MAPK phosphorylation. On the other hand, inhibition of p38 MAPK phosphorylation has no effect on IκBα phosphorylation, indicating a divergence in the signaling pathway originating from CD40 upon its ligation. In functional studies, inhibition of IκBα phosphorylation reverses sCD40L-induced platelet activation and potentiation of platelet aggregation in response to a sub-threshold concentration of collagen. This study demonstrates that the sCD40L/CD40 axis triggers NF-κB activation in platelets. This signaling pathway plays a critical role in platelet activation and aggregation upon sCD40L stimulation and may represent an important target against thrombo-inflammatory disorders.

U.S. Nuclear Regulatory Commission human factors program plan

International Nuclear Information System (INIS)

1986-04-01

The purpose of the U.S. Nuclear Regulatory Commission (NRC) Human Factors Program Plan is to ensure that proper consideration is given to human factors in the design and operation of nuclear facilities. This revised plan addresses human factors issues related to the operation of nuclear power plants (NPPs). The three issues of concern are (1) the activities planned to provide the technical bases to resolve the remaining tasks related to human factors as described in NUREG-0660, The NRC Action Plan Developed as a Result of the TMI-2 Accident, and NUREG-0737, Clarification of TMI Action Plan Requirements; (2) the need to address the additional human factors efforts that were identified during implementation of the Action Plan; and (3) the actual fulfillment of those developmental activities specified in Revision 1 of this plan. The plan represents a systematic approach for addressing high priority human factors concerns important to NPP safety in FY 1986 through 1987

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

Macromolecular complexes of lysozyme with kappa carrageenan

NARCIS (Netherlands)

Antonov, Y.A.; Zhuravleva, I.L.; Cardinaels, R.; Moldenaers, P.

2018-01-01

We present a structural study of the complexation and binding of lysozyme (Lys) with kappa carrageenan (kCG) by means of turbidity measurements, phase analysis, dynamic and electrophoretic light scattering, differential scanning microcalorimetry (DSMC), confocal laser scanning (CLSM) microscopy,

A new gene in A. rubens: A sea star Ig kappa gene.

Science.gov (United States)

Vincent, Nadine; Osteras, Magne; Otten, Patricia; Leclerc, Michel

2014-12-01

The sea star Asterias rubens reacts specifically to the antigen:HRP (horse-radish peroxydase) and produces an antibody anti-HRP. We previously identified a candidate Ig kappa gene corresponding to this manuscript. We show now the gene referred to as: "sea star Ig kappa gene in its specificity".

Gnotobiotic IL-10; NF-kappaB mice develop rapid and severe colitis following Campylobacter jejuni infection.

Directory of Open Access Journals (Sweden)

Elisabeth Lippert

2009-10-01

Full Text Available Limited information is available on the molecular mechanisms associated with Campylobacter jejuni (C. jejuni induced food-borne diarrheal illnesses. In this study, we investigated the function of TLR/NF-kappaB signaling in C. jejuni induced pathogenesis using gnotobiotic IL-10(-/-; NF-kappaB(EGFP mice. In vitro analysis showed that C. jejuni induced IkappaB phosphorylation, followed by enhanced NF-kappaB transcriptional activity and increased IL-6, MIP-2alpha and NOD2 mRNA accumulation in infected-mouse colonic epithelial cells CMT93. Importantly, these events were blocked by molecular delivery of an IkappaB inhibitor (Ad5IkappaBAA. NF-kappaB signalling was also important for C.jejuni-induced cytokine gene expression in bone marrow-derived dendritic cells. Importantly, C. jejuni associated IL-10(-/-; NF-kappaB(EGFP mice developed mild (day 5 and severe (day 14 ulcerating colonic inflammation and bloody diarrhea as assessed by colonoscopy and histological analysis. Macroscopic analysis showed elevated EGFP expression indicating NF-kappaB activation throughout the colon of C. jejuni associated IL-10(-/-; NF-kappaB(EGFP mice, while fluorescence microscopy revealed EGFP positive cells to be exclusively located in lamina propria mononuclear cells. Pharmacological NF-kappaB inhibition using Bay 11-7085 did not ameliorate C. jejuni induced colonic inflammation. Our findings indicate that C. jejuni induces rapid and severe intestinal inflammation in a susceptible host that correlates with enhanced NF-kappaB activity from lamina propria immune cells.

Protective effect of nuclear factor E2-related factor 2 on inflammatory cytokine response to brominated diphenyl ether-47 in the HTR-8/SVneo human first trimester extravillous trophoblast cell line.

Science.gov (United States)

Park, Hae-Ryung; Loch-Caruso, Rita

2014-11-15

Polybrominated diphenyl ethers (PBDEs) are widely used flame retardants, and BDE-47 is a prevalent PBDE congener detected in human tissues. Exposure to PBDEs has been linked to adverse pregnancy outcomes in humans. Although the underlying mechanisms of adverse birth outcomes are poorly understood, critical roles for oxidative stress and inflammation are implicated. The present study investigated antioxidant responses in a human extravillous trophoblast cell line, HTR-8/SVneo, and examined the role of nuclear factor E2-related factor 2 (Nrf2), an antioxidative transcription factor, in BDE-47-induced inflammatory responses in the cells. Treatment of HTR-8/SVneo cells with 5, 10, 15, and 20μM BDE-47 for 24h increased intracellular glutathione (GSH) levels compared to solvent control. Treatment of HTR-8/SVneo cells with 20μM BDE-47 for 24h induced the antioxidant response element (ARE) activity, indicating Nrf2 transactivation by BDE-47 treatment, and resulted in differential expression of redox-sensitive genes compared to solvent control. Pretreatment with tert-butyl hydroquinone (tBHQ) or sulforaphane, known Nrf2 inducers, reduced BDE-47-stimulated IL-6 release with increased ARE reporter activity, reduced nuclear factor kappa B (NF-κB) reporter activity, increased GSH production, and stimulated expression of antioxidant genes compared to non-Nrf2 inducer pretreated groups, suggesting that Nrf2 may play a protective role against BDE-47-mediated inflammatory responses in HTR-8/SVneo cells. These results suggest that Nrf2 activation significantly attenuated BDE-47-induced IL-6 release by augmentation of cellular antioxidative system via upregulation of Nrf2 signaling pathways, and that Nrf2 induction may be a potential therapeutic target to reduce adverse pregnancy outcomes associated with toxicant-induced oxidative stress and inflammation. Copyright © 2014 Elsevier Inc. All rights reserved.

Bay11-7082 attenuates neuropathic pain via inhibition of nuclear factor-kappa B and nucleotide-binding domain-like receptor protein 3 inflammasome activation in dorsal root ganglions in a rat model of lumbar disc herniation

Directory of Open Access Journals (Sweden)

Zhang AL

2017-02-01

Full Text Available Ailiang Zhang, Kun Wang, Lianghua Ding, Xinnan Bao, Xuan Wang, Xubin Qiu, Jinbo Liu Spine Surgery, Third Affiliated Hospital of Soochow University, Changzhou, People’s Republic of China Abstract: Lumbar disc herniation (LDH is an important cause of radiculopathy, but the underlying mechanisms are incompletely understood. Many studies suggested that local inflammation, rather than mechanical compression, results in radiculopathy induced by LDH. On the molecular and cellular level, nuclear factor-kappa B (NF-κB and nucleotide-binding domain-like receptor protein 3 (NLRP3 inflammasome have been implicated in the regulation of neuroinflammation formation and progression. In this study, the autologous nucleus pulposus (NP was implanted in the left L5 dorsal root ganglion (DRG to mimic LDH in rats. We investigated the expression of NF-κB and the components of NLRP3 inflammasome in the DRG neurons in rats. Western blotting and immunofluorescence for the related molecules, including NLRP3, apoptosis-associated speck-like protein containing caspase-1 activator domain (ASC, caspase-1, interleukin (IL-1β, IL-18, IκBα, p-IκBα, p65, p-p65, and calcitonin gene-related peptide (CGRP were examined. In the NP-treated group, the activations of NLRP3, ASC, caspase-1, IL-1β, IL-18, p-IκBα, and p-p65 in DRG neurons in rats were elevated at 1 day after surgery, and the peak occurred at 7 days. Treatment with Bay11-7082, an inhibitor of the actions of IKK-β, was able to inhibit expression and activation of the molecules (NLRP3, ASC, caspase-1, IL-1β, IL-18, p-IκBα, and p-p65 and relieve the pain in rats. Our study shows that NF-κB and NLRP3 inflammasome are involved in the maintenance of NP-induced pain, and that Bay11-7082 could alleviate mechanical allodynia and thermal hyperalgesia by inhibiting NF-κB and NLRP3 inflammasome activation. Keywords: pain, NLRP3, NF-κB, dorsal root ganglion, nucleus pulposus

Up-stream events in the nuclear factor κB activation cascade in response to sparsely ionizing radiation

Science.gov (United States)

Hellweg, Christine E.; Langen, Britta; Klimow, Galina; Ruscher, Roland; Schmitz, Claudia; Baumstark-Khan, Christa; Reitz, Günther

2009-10-01

Radiation is a potentially limiting factor for manned long-term space missions. Prolonged exposure to galactic cosmic rays may shorten the healthy life-span after return to Earth due to cancer induction. During the mission, a solar flare can be life threatening. For better risk estimation and development of appropriate countermeasures, the study of the cellular radiation response is necessary. Since apoptosis may be a mechanism the body uses to eliminate damaged cells, the induction by cosmic radiation of the nuclear anti-apoptotic transcription factor nuclear factor κB (NF-κB) could influence the cancer risk of astronauts exposed to cosmic radiation by improving the survival of radiation-damaged cells. In previous studies using a screening assay for the detection of NF-κB-dependent gene induction (HEK-pNF-κB-d2EGFP/Neo cells), the activation of this transcription factor by heavy ions was shown [Baumstark-Khan, C., Hellweg, C.E., Arenz, A., Meier, M.M. Cellular monitoring of the nuclear factor kappa B pathway for assessment of space environmental radiation. Radiat. Res. 164, 527-530, 2005]. Studies with NF-κB inhibitors can map functional details of the NF-κB pathway and the influence of radiation-induced NF-κB activation on various cellular outcomes such as survival or cell cycle arrest. In this work, the efficacy and cytotoxicity of four different NF-κB inhibitors, caffeic acid phenethyl ester (CAPE), capsaicin, the proteasome inhibitor MG-132, and the cell permeable peptide NF-κB SN50 were analyzed using HEK-pNF-κB-d2EGFP/Neo cells. In the recommended concentration range, only CAPE displayed considerable cytotoxicity. CAPE and capsaicin partially inhibited NF-κB activation by the cytokine tumor necrosis factor α. MG-132 completely abolished the activation and was therefore used for experiments with X-rays. NF-κB SN-50 could not reduce NF-κB dependent expression of the reporter destabilized Enhanced Green Fluorescent Protein (d2EGFP). MG-132

Expression of a truncated receptor protein tyrosine phosphatase kappa in the brain of an adult transgenic mouse

DEFF Research Database (Denmark)

Shen, P; Canoll, P D; Sap, J

1999-01-01

processes such as axonal growth and target recognition, as has been demonstrated for certain Drosophila RPTPs. The brain distribution of RPTP-kappa-expressing cells has not been determined, however. In a gene-trap mouse model with a beta-gal+neo (beta-geo) insertion in the endogenous RPTP-kappa gene......-6596]. Nevertheless, since the transgene's expression is driven by the endogenous RPTP-kappa promoter, distribution of the truncated RPTP-kappa/beta-geo fusion protein should reflect the regional and cellular expression of wild-type RPTP-kappa, and thus may identify sites where RPTP-kappa is important. Towards...... that goal, we have used this mouse model to map the distribution of the truncated RPTP-kappa/beta-geo fusion protein in the adult mouse brain using beta-galactosidase as a marker enzyme. Visualization of the beta-galactosidase activity revealed a non-random pattern of expression, and identified cells...

Human placenta: relative content of antibodies of different classes and subclasses (IgG1-IgG4) containing lambda- and kappa-light chains and chimeric lambda-kappa-immunoglobulins.

Science.gov (United States)

Lekchnov, Evgenii A; Sedykh, Sergey E; Dmitrenok, Pavel S; Buneva, Valentina N; Nevinsky, Georgy A

2015-06-01

The specific organ placenta is much more than a filter: it is an organ that protects, feeds and regulates the growth of the embryo. Affinity chromatography, ELISA, SDS-PAGE and matrix-assisted laser desorption ionization mass spectrometry were used. Using 10 intact human placentas deprived of blood, a quantitative analysis of average relative content [% of total immunoglobulins (Igs)] was carried out for the first time: (92.7), IgA (2.4), IgM (2.5), kappa-antibodies (51.4), lambda-antibodies (48.6), IgG1 (47.0), IgG2 (39.5), IgG3 (8.8) and IgG4 (4.3). It was shown for the first time that placenta contains sIgA (2.5%). In the classic paradigm, Igs represent products of clonal B-cell populations, each producing antibodies recognizing a single antigen. There is a common belief that IgGs in mammalian biological fluids are monovalent molecules having stable structures and two identical antigen-binding sites. However, similarly to human milk Igs, placenta antibodies undergo extensive half-molecule exchange and the IgG pool consists of 43.5 ± 15.0% kappa-kappa-IgGs and 41.6 ± 17.0% lambda-lambda-IgGs, while 15.0 ± 4.0% of the IgGs contained both kappa- and lambda-light chains. Kappa-kappa-IgGs and lambda-lambda-IgGs contained, respectively (%): IgG1 (47.7 and 34.4), IgG2 (36.3 and 44.5), IgG3 (7.4 and 11.8) and IgG4 (7.5 and 9.1), while chimeric kappa-lambda-IgGs consisted of (%): 43.5 IgG1, 41.0 IgG2, 5.6 IgG3 and 7.9 IgG4. Our data are indicative of the possibility of half-molecule exchange between placenta IgGs of various subclasses, raised against different antigens, which explains a very well-known polyspecificity and cross-reactivity of different human IgGs. © The Japanese Society for Immunology. 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

US Nuclear Regulatory Commission human-factors program plan

International Nuclear Information System (INIS)

1983-08-01

The purpose of the NRC Human Factors Program Plan is to ensure that proper consideration is given to human factors in the design, operation, and maintenance of nuclear facilities. This initial plan addresses nuclear power plants (NPP) and describes (1) the technical assistance and research activities planned to provide the technical bases for the resolution of the remaining human factors related tasks described in NUREG-0660, The NRC Action Plan Developed as a Result of the TMI-2 Accident, and NUREG-0737, Clarification of TMI Action Plan Requirements, and (2) the additional human factors efforts identified during implementation of the Action Plan that should receive NRC attention. The plan represents a systematic and comprehensive approach for addressing human factors concerns important to NPP safety in the FY-83 through FY-85 time frame

DMPD: New insights into NF-kappaB regulation and function. [Dynamic Macrophage Pathway CSML Database

Lifescience Database Archive (English)

Full Text Available 18775672 New insights into NF-kappaB regulation and function. Sun SC, Ley SC. Trend...ction. PubmedID 18775672 Title New insights into NF-kappaB regulation and function....s Immunol. 2008 Oct;29(10):469-78. Epub 2008 Sep 3. (.png) (.svg) (.html) (.csml) Show New insights into NF-kappaB regulation and fun

Common gene variants in the tumor necrosis factor (TNF and TNF receptor superfamilies and NF-kB transcription factors and non-Hodgkin lymphoma risk.

Directory of Open Access Journals (Sweden)

Sophia S Wang

Full Text Available A promoter polymorphism in the pro-inflammatory cytokine tumor necrosis factor (TNF (TNF G-308A is associated with increased non-Hodgkin lymphoma (NHL risk. The protein product, TNF-alpha, activates the nuclear factor kappa beta (NF-kappaB transcription factor, and is critical for inflammatory and apoptotic responses in cancer progression. We hypothesized that the TNF and NF-kappaB pathways are important for NHL and that gene variations across the pathways may alter NHL risk.We genotyped 500 tag single nucleotide polymorphisms (SNPs from 48 candidate gene regions (defined as 20 kb 5', 10 kb 3' in the TNF and TNF receptor superfamilies and the NF-kappaB and related transcription factors, in 1946 NHL cases and 1808 controls pooled from three independent population-based case-control studies. We obtained a gene region-level summary of association by computing the minimum p-value ("minP test". We used logistic regression to compute odds ratios and 95% confidence intervals for NHL and four major NHL subtypes in relation to SNP genotypes and haplotypes. For NHL, the tail strength statistic supported an overall relationship between the TNF/NF-kappaB pathway and NHL (p = 0.02. We confirmed the association between TNF/LTA on chromosome 6p21.3 with NHL and found the LTA rs2844484 SNP most significantly and specifically associated with the major subtype, diffuse large B-cell lymphoma (DLBCL (p-trend = 0.001. We also implicated for the first time, variants in NFKBIL1 on chromosome 6p21.3, associated with NHL. Other gene regions identified as statistically significantly associated with NHL included FAS, IRF4, TNFSF13B, TANK, TNFSF7 and TNFRSF13C. Accordingly, the single most significant SNPs associated with NHL were FAS rs4934436 (p-trend = 0.0024, IRF4 rs12211228 (p-trend = 0.0026, TNFSF13B rs2582869 (p-trend = 0.0055, TANK rs1921310 (p-trend = 0.0025, TNFSF7 rs16994592 (p-trend = 0.0024, and TNFRSF13C rs6002551 (p-trend = 0.0074. All associations were

Organizational factors in nuclear safety

International Nuclear Information System (INIS)

Wilpert, Bernhard

2000-01-01

The overall picture of factors which contributed to the event presents a panorama of a NPP where organizational and managerial characteristics were intricately intertwined and emerged as crucial for a general deterioration of the plant's capabilities to continually correct its deficiencies and optimize its operations. In the following author shall attempt to first cover various important efforts to modeling organizational factors relevant to safety. The second part of my presentation will offer an attempt towards an integrative model. The third part concludes with an agenda for research and practice. Most of the twelve different approaches above attempt to consider safety relevant organizational factors by way of pragmatic classifications. Together with their sub-categories we can count close to 160 different factors on various levels of abstraction. This is tantamount to say that most approaches lack systematic theoretical underpinnings. Thus then arises the question whether we need to develop a generic model, which promises to encompass these three major approaches altogether. Practical issues emerge particularly in the domain of organizational development, i.e. the goal oriented efforts to change the structures and the functioning of nuclear operations in such a way that the desired outputs in terms safety and reliability result in a sustained fashion. Again, these practical concerns are intimately related to developments and advances in theory and methodology. Only a close cooperation among scientists from various disciplines and of practitioners holds the promise of adequately understanding and use of organizational factors in future improving the safety record of nuclear industry worldwide. (S.Y.)

The Nuclear Energy Factor In Indian Politics

Directory of Open Access Journals (Sweden)

A. A. Boyko

2017-01-01

Full Text Available Nuclear energy is a key branch of the world power system. The nuclear energy development is viewed by India as one of the ways to resolve the problem of the energy supply. In 2008 the country gained more opportunities for developing nuclear power sector and solving the national power deficit problem after NSG lifted restrictions on nuclear trade. This resulted in foreign companies emerging on the Indian nuclear market. In 2011 after the major emergency at Fukushima Daiichi Nuclear Power Plant in Japan India faced numerous anti-nuclear protests backed by NGOs, including those with foreign funding, and political parties. The article deals with the question of the political role this anti-nuclear opposition plays in India. According to some researchers the protests are organized by the competitors in order to compromise the business of a Russian company Rosatom in India. However, such demonstrations are spread throughout the country and directed against the competitors of Rosatom as well. The article comes to conclusion that the protests are just a reflection of the political fights in India where nuclear energy is a significant political factor.

DMPD: Ubiquitin: tool and target for intracellular NF-kappaB inhibitors. [Dynamic Macrophage Pathway CSML Database

Lifescience Database Archive (English)

Full Text Available 16982211 Ubiquitin: tool and target for intracellular NF-kappaB inhibitors. Wullaer...vg) (.html) (.csml) Show Ubiquitin: tool and target for intracellular NF-kappaB inhibitors. PubmedID 1698221...1 Title Ubiquitin: tool and target for intracellular NF-kappaB inhibitors. Author

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

Expression of a truncated receptor protein tyrosine phosphatase kappa in the brain of an adult transgenic mouse

DEFF Research Database (Denmark)

Shen, P; Canoll, P D; Sap, J

1999-01-01

that goal, we have used this mouse model to map the distribution of the truncated RPTP-kappa/beta-geo fusion protein in the adult mouse brain using beta-galactosidase as a marker enzyme. Visualization of the beta-galactosidase activity revealed a non-random pattern of expression, and identified cells......-6596]. Nevertheless, since the transgene's expression is driven by the endogenous RPTP-kappa promoter, distribution of the truncated RPTP-kappa/beta-geo fusion protein should reflect the regional and cellular expression of wild-type RPTP-kappa, and thus may identify sites where RPTP-kappa is important. Towards...

Spectroscopy of the fractional vortex eigenfrequency in a long Josephson 0-{kappa} junction

Energy Technology Data Exchange (ETDEWEB)

Buckenmaier, K.; Gaber, T.; Schittenhelm, I.; Kleiner, R.; Koelle, D.; Goldobin, E. [Physikalisches Inst., Experimentalphysik II, Univ. Tuebingen (Germany); Siegel, M. [Univ. Karlsruhe (Germany). Inst. fuer Mikro- und Nanoelektronische Systeme

2007-07-01

In long Josephson junctions with a {kappa}-phase discontinuity, created by two current injectors, a fractional Josephson vortex (FJV) is spontaneously formed at the interface between the 0- and {kappa}-part. A FJV carries an arbitrary fraction {phi}/{phi}{sub 0}={kappa}/2{pi} of the magnetic flux quantum {phi}{sub 0}{approx}2.07 x 10{sup -15} Wb. In contrast to fluxons, FJVs are pinned at the discontinuity point, but in underdamped systems they are able to oscillate around their equilibrium point with characteristic eigenfrequencies. To experimentally determine the eigenfrequency we stimulated a FJV by irradiating our sample with microwaves. At resonance the junction switches to the resistive state. A measurement of the switching probability thus allows to determine the FJV eigenfrequency as a function of bias current and {kappa}. We compare our results with the prediction of the perturbed sine-Gordon equation. (orig.)

Copper Metabolism Domain-Containing 1 Represses Genes That Promote Inflammation and Protects Mice From Colitis and Colitis-Associated Cancer

NARCIS (Netherlands)

Li, Haiying; Chan, Lillienne; Bartuzi, Paulina; Melton, Shelby D.; Weber, Axel; Ben-Shlomo, Shani; Varol, Chen; Raetz, Megan; Mao, Xicheng; Starokadomskyy, Petro; van Sommeren, Suzanne; Mokadem, Mohamad; Schneider, Heike; Weisberg, Reid; Westra, Harm-Jan; Esko, Tonu; Metspalu, Andres; Magadi Gopalaiah, Vinod Kumar; Faubion, William A.; Yarovinsky, Felix; Hofker, Marten; Wijmenga, Cisca; Kracht, Michael; Franke, Lude; Aguirre, Vincent; Weersma, Rinse K.; Gluck, Nathan; van de Sluis, Bart; Burstein, Ezra

BACKGROUND & AIMS: Activation of the transcription factor nuclear factor-kappa B (NF-kappa B) has been associated with the development of inflammatory bowel disease (IBD). Copper metabolism MURR1 domain containing 1 (COMMD1), a regulator of various transport pathways, has been shown to limit

Colloidal gas-liquid condensation of polystyrene latex particles with intermediate kappa a values (5 to 160, a > kappa(-1)).

Science.gov (United States)

Ishikawa, Masamichi; Kitano, Ryota

2010-02-16

Polystyrene latex particles showed gas-liquid condensation under the conditions of large particle radius (a > kappa(-1)) and intermediate kappa a, where kappa is the Debye-Hückel parameter and a is the particle radius. The particles were dissolved in deionized water containing ethanol from 0 to 77 vol %, settled to the bottom of the glass plate within 1 h, and then laterally moved toward the center of a cell over a 20 h period in reaching a state of equilibrium condensation. All of the suspensions that were 1 and 3 microm in diameter and 0.01-0.20 vol % in concentration realized similar gas-liquid condensation with clear gas-liquid boundaries. In 50 vol % ethanol solvent, additional ethanol was added to enhance the sedimentation force so as to restrict the particles in a monoparticle layer thickness. The coexistence of gas-liquid-solid (crystalline solid) was microscopically recognized from the periphery to the center of the condensates. A phase diagram of the gas-liquid condensation was created as a function of KCl concentration at a particle diameter of 3 microm, 0.10 vol % concentration, and 50:50 water/ethanol solvent at room temperature. The miscibility gap was observed in the concentration range from 1 to 250 microM. There was an upper limit of salt concentration where the phase separation disappeared, showing nearly critical behavior of macroscopic density fluctuation from 250 microM to 1 mM. These results add new experimental evidence to the existence of colloidal gas-liquid condensation and specify conditions of like-charge attraction between particles.

Lactobacillus rhamnosus GR-1 enhances NF-kappaB activation in Escherichia coli-stimulated urinary bladder cells through TLR4

Directory of Open Access Journals (Sweden)

Karlsson Mattias

2012-01-01

modulated the activation of the NF-kappaB through increased levels of TLR4 on the bladder cells and altered subsequent release of cytokines from urothelial cells. By influencing immunological factors such as TLR4, important in the process of fighting pathogens, lactobacilli could facilitate pathogen recognition and infection clearance.

A note on the kappa statistic for clustered dichotomous data.

Science.gov (United States)

Zhou, Ming; Yang, Zhao

2014-06-30

The kappa statistic is widely used to assess the agreement between two raters. Motivated by a simulation-based cluster bootstrap method to calculate the variance of the kappa statistic for clustered physician-patients dichotomous data, we investigate its special correlation structure and develop a new simple and efficient data generation algorithm. For the clustered physician-patients dichotomous data, based on the delta method and its special covariance structure, we propose a semi-parametric variance estimator for the kappa statistic. An extensive Monte Carlo simulation study is performed to evaluate the performance of the new proposal and five existing methods with respect to the empirical coverage probability, root-mean-square error, and average width of the 95% confidence interval for the kappa statistic. The variance estimator ignoring the dependence within a cluster is generally inappropriate, and the variance estimators from the new proposal, bootstrap-based methods, and the sampling-based delta method perform reasonably well for at least a moderately large number of clusters (e.g., the number of clusters K ⩾50). The new proposal and sampling-based delta method provide convenient tools for efficient computations and non-simulation-based alternatives to the existing bootstrap-based methods. Moreover, the new proposal has acceptable performance even when the number of clusters is as small as K = 25. To illustrate the practical application of all the methods, one psychiatric research data and two simulated clustered physician-patients dichotomous data are analyzed. Copyright © 2014 John Wiley & Sons, Ltd.

Molecular cloning and expression of bovine kappa-casein in Escherichia coli

International Nuclear Information System (INIS)

Kang, Y.C.; Richardson, T.

1988-01-01

A cDNA library was constructed using poly(A) + RNA from bovine mammary gland. This cDNA library of 6000 clones was screened employing colony hybridization using 32 P-labelled oligonucleotide probes and restriction endonuclease mapping. The cDNA from the selected plasmid, pKR76, was sequenced using the dideoxy-chain termination method. The cDNA insert of pKR76 carries the full-length sequence, which codes for mature kappa-casein protein. The amino acid sequence deduced from the cDNA sequence fits the published amino acid sequence with three exceptions; the reported pyroglutamic acid at position 1, tyrosine at position 35, and aspartic acid at position 81 are, respectively, a glutamine, a histidine, and an asparagine in the clone containing pKR76. The MspI-, NlaIV-cleaved fragment (630 base pair) from the kappa-casein cDNA insert has been subcloned into expression vectors pUC18 and pKK233-2, which contain a lac promoter and a trc promoter, respectively. Escherichia coli cells carrying the recombinant expression plasmids were shown to produce kappa-casein protein having the expected mobility on sodium dodecyl sulfate-polyacrylamide gel electrophoresis and being recognized by specific antibodies raised against natural bovine kappa-casein

Polymorphisms in NFKB1 and TLR4 and Interaction with Dietary and Life Style Factors in Relation to Colorectal Cancer in a Danish Prospective Case-Cohort Study

DEFF Research Database (Denmark)

Kopp, Tine Iskov; Andersen, Vibeke; Tjoøneland, Anne

2015-01-01

Maintenance of a balance between commensal bacteria and the mucosal immune system is crucial and intestinal dysbiosis may be a key event in the pathogenesis of colorectal cancer (CRC). The toll-like receptor 4 (TLR4) is an important pattern-recognition receptor that regulates inflammation...... and barrier function in the gut by a mechanism that involves activation of the nuclear factor-kappa B (NF-kappa B) transcription factor. Dietary and life style factors may impact these functions. We therefore used a Danish prospective case-cohort study of 1010 CRC cases and 1829 randomly selected participants...... from the Danish Diet, Cancer and Health cohort to investigate three polymorphisms in NFKB1 and TLR4 and their possible interactions with diet and life style factors in relation to risk of CRC. Homozygous carriage of the variant allele of the TLR4/rs5030728 polymorphism was associated with increased...

Uranium - a factor limiting nuclear energy?

International Nuclear Information System (INIS)

Ohnemus, J.

2006-01-01

Nuclear power has been back as a topic of public debate since early this year. A special subject under discussion is the extension of nuclear power plant life. Hardly had it been on the agenda, when interested parties announced that this st ep was impossible because uranium reserves were no longer sufficient. A variety of terms are being used in this discussion without their meaning being taken int o account: stocks, resources, and reserves. To clarify the situation, this artic le outlines important aspects of short and long term uranium supplies, and analy zes their meaning. Here are some of the most important issues under consideration: - For what period of time is there really enough uranium? - Is uranium becoming the limiting factor in the use of nuclear power? - Is uranium really a 'sustainable' energy resource? - Will higher prices extend the range? - What is the in fluence of the price of uranium on the cost of electricity generation? Among oth er results, it is found that comprehensive sources of low-price uranium and nucl ear fuels are, or can be made, available worldwide. Consequently, the 'range' is beyond the time frames currently mentioned, also as a function of technological factors, i.e. reaching several hundred years. It is also important to note that nuclear power - ensures greater independence of volatile imported sources, - guarantees reliably low electricity prices, - has a huge potential of environmental protection, and - is a clean source of energy. (orig.)

Expression of inducible nitric oxide synthase in endotoxemic rat hepatocytes is dependent on the cellular glutathione status

NARCIS (Netherlands)

Vos, TA; van Goor, H; Tuyt, L; de Jager-Krikken, A; Leuvenink, R; Kuipers, F; Jansen, PLM; Moshage, H

The inducible nitric oxide synthase (iNOS) promoter contains nuclear factor kappa B (NF-kappa B) binding sites. NF-kappa B activation is determined, in part, by the intracellular redox status, The aim of this study was to determine the importance of the cellular glutathione status in relation to

Significant differences in physicochemical properties of human immunoglobulin kappa and lambda CDR3 regions

Directory of Open Access Journals (Sweden)

Catherine L Townsend

2016-09-01

Full Text Available Antibody variable regions are composed of a heavy and a light chain and in humans there are two light chain isotypes: kappa and lambda. Despite their importance in receptor editing, the light chain is often overlooked in the antibody literature, with the focus being on the heavy chain CDR-H3 region. In this paper, we set out to investigate the physicochemical and structural differences between human kappa and lambda light chain CDR regions. We constructed a dataset containing over 29,000 - light chain variable region sequences from IgM-transcribing, newly formed B cells isolated from human bone marrow and peripheral blood. We also used a published human naïve dataset to investigate the CDR-H3 properties of heavy chains paired with kappa and lambda light chains, and probed the Protein Data Bank (PDB to investigate the structural differences between kappa and lambda antibody CDR regions. We found that kappa and lambda light chains have very different CDR physicochemical and structural properties, whereas the heavy chains with which they are paired do not differ significantly. We also observed that the mean CDR3 N nucleotide addition in the kappa, lambda and heavy chain gene rearrangements are correlated within donors, but can differ between donors. This indicates that TdT may work with differing efficiencies between different people, but the same efficiency in the different classes of immunoglobulin chain within one person. We have observed large differences in the physicochemical and structural properties of kappa and lambda light chain CDR regions. This may reflect different roles in the humoral immune response.

Significant Differences in Physicochemical Properties of Human Immunoglobulin Kappa and Lambda CDR3 Regions.

Science.gov (United States)

Townsend, Catherine L; Laffy, Julie M J; Wu, Yu-Chang Bryan; Silva O'Hare, Joselli; Martin, Victoria; Kipling, David; Fraternali, Franca; Dunn-Walters, Deborah K

2016-01-01

Antibody variable regions are composed of a heavy and a light chain, and in humans, there are two light chain isotypes: kappa and lambda. Despite their importance in receptor editing, the light chain is often overlooked in the antibody literature, with the focus being on the heavy chain complementarity-determining region (CDR)-H3 region. In this paper, we set out to investigate the physicochemical and structural differences between human kappa and lambda light chain CDR regions. We constructed a dataset containing over 29,000 light chain variable region sequences from IgM-transcribing, newly formed B cells isolated from human bone marrow and peripheral blood. We also used a published human naïve dataset to investigate the CDR-H3 properties of heavy chains paired with kappa and lambda light chains and probed the Protein Data Bank to investigate the structural differences between kappa and lambda antibody CDR regions. We found that kappa and lambda light chains have very different CDR physicochemical and structural properties, whereas the heavy chains with which they are paired do not differ significantly. We also observed that the mean CDR3 N nucleotide addition in the kappa, lambda, and heavy chain gene rearrangements are correlated within donors but can differ between donors. This indicates that terminal deoxynucleotidyl transferase may work with differing efficiencies between different people but the same efficiency in the different classes of immunoglobulin chain within one person. We have observed large differences in the physicochemical and structural properties of kappa and lambda light chain CDR regions. This may reflect different roles in the humoral immune response.

Method for rapidly determining a pulp kappa number using spectrophotometry

Science.gov (United States)

Chai, Xin-Sheng; Zhu, Jun Yong

2002-01-01

A system and method for rapidly determining the pulp kappa number through direct measurement of the potassium permanganate concentration in a pulp-permanganate solution using spectrophotometry. Specifically, the present invention uses strong acidification to carry out the pulp-permanganate oxidation reaction in the pulp-permanganate solution to prevent the precipitation of manganese dioxide (MnO.sub.2). Consequently, spectral interference from the precipitated MnO.sub.2 is eliminated and the oxidation reaction becomes dominant. The spectral intensity of the oxidation reaction is then analyzed to determine the pulp kappa number.

[{sup 11}C]-MeJDTic: a novel radioligand for {kappa}-opioid receptor positron emission tomography imaging

Energy Technology Data Exchange (ETDEWEB)

Poisnel, Geraldine; Oueslati, Farhana; Dhilly, Martine; Delamare, Jerome [Groupe de Developpements Methodologiques en Tomographie par Emission de Positons, DSV/DRM UMR CEA 2E, Universite de Caen-Basse Normandie, Centre Cyceron, 14074 Caen Cedex (France); Perrio, Cecile [Groupe de Developpements Methodologiques en Tomographie par Emission de Positons, DSV/DRM UMR CEA 2E, Universite de Caen-Basse Normandie, Centre Cyceron, 14074 Caen Cedex (France)], E-mail: perrio@cyceron.fr; Debruyne, Daniele [Groupe de Developpements Methodologiques en Tomographie par Emission de Positons, DSV/DRM UMR CEA 2E, Universite de Caen-Basse Normandie, Centre Cyceron, 14074 Caen Cedex (France)], E-mail: debruyne@cyceron.fr; Barre, Louisa [Groupe de Developpements Methodologiques en Tomographie par Emission de Positons, DSV/DRM UMR CEA 2E, Universite de Caen-Basse Normandie, Centre Cyceron, 14074 Caen Cedex (France)

2008-07-15

Introduction: Radiopharmaceuticals that can bind selectively the {kappa}-opioid receptor may present opportunities for staging clinical brain disorders and evaluating the efficiency of new therapies related to stroke, neurodegenerative diseases or opiate addiction. The N-methylated derivative of JDTic (named MeJDTic), which has been recently described as a potent and selective antagonist of {kappa}-opioid receptor in vitro, was labeled with carbon-11 and evaluated for in vivo imaging the {kappa}-opioid receptor in mice. Methods: [{sup 11}C]-MeJDTic was prepared by methylation of JDTic with [{sup 11}C]-methyl triflate. The binding of [{sup 11}C]-MeJDTic to {kappa}-opioid receptor was investigated ex vivo by biodistribution and competition studies using nonfasted male CD1 mice. Results: [{sup 11}C]-MeJDTic exhibited a high and rapid distribution in peripheral organs. The uptake was maximal in lung where the {kappa} receptor is largely expressed. [{sup 11}C]-MeJDTic rapidly crossed the blood-brain barrier and accumulated in the brain regions of interest (hypothalamus). The parent ligand remained the major radioactive compound in brain during the experiment. Chase studies with U50,488 (a {kappa} referring agonist), morphine (a {mu} agonist) and naltrindole (a {delta} antagonist) demonstrated that this uptake was the result of specific binding to the {kappa}-opioid receptor. Conclusion: These findings suggested that [{sup 11}C]-MeJDTic appeared to be a promising selective 'lead' radioligand for {kappa}-opioid receptor PET imaging.

Separating form factor and nuclear model effects in quasielastic neutrino-nucleus scattering

Science.gov (United States)

Wieske, Joseph

2017-09-01

When studying neutrino oscillations an understanding of charged current quasielastic (CCQE) neutrino-nucleus scattering is imperative. This interaction depends on a nuclear model as well as knowledge of form factors. In the past, CCQE data from the MiniBooNE experiment was analyzed assuming the Relativistic Fermi Gas (RFG) nuclear model, an axial dipole form factor in, and using the the z-expansion for the axial form factor in. We present the first analysis that combines a non-RFG nuclear model, in particular the Correlated Fermi Gas nuclear model (CFG) of, and the z expansion for the axial form factor. This will allow us to separate form factor and nuclear model effects in CCQE scattering. This project was supported through the Wayne State University REU program under NSF Grant PHY-1460853 and by the DOE Grant DE-SC0007983.

Quince (Cydonia oblonga Miller) peel polyphenols modulate LPS-induced inflammation in human THP-1-derived macrophages through NF-{kappa}B, p38MAPK and Akt inhibition

Energy Technology Data Exchange (ETDEWEB)

Essafi-Benkhadir, Khadija [Laboratoire d' epidemiologie Moleculaire et Pathologie Experimentale Appliquee Aux Maladies Infectieuses, Institut Pasteur de Tunis (Tunisia); Refai, Amira [Laboratoire de Recherche sur la Transmission, le Controle et l' immunobiologie des Infections, Institut Pasteur de Tunis (Tunisia); Riahi, Ichrak [Laboratoire d' epidemiologie Moleculaire et Pathologie Experimentale Appliquee Aux Maladies Infectieuses, Institut Pasteur de Tunis (Tunisia); Fattouch, Sami [Laboratory LIP-MB National Institute of Applied Sciences and Technology, Tunis (Tunisia); Karoui, Habib [Laboratoire d' epidemiologie Moleculaire et Pathologie Experimentale Appliquee Aux Maladies Infectieuses, Institut Pasteur de Tunis (Tunisia); Essafi, Makram, E-mail: makram.essafi@pasteur.rns.tn [Laboratoire de Recherche sur la Transmission, le Controle et l' immunobiologie des Infections, Institut Pasteur de Tunis (Tunisia)

2012-02-03

Highlights: Black-Right-Pointing-Pointer Quince peel polyphenols inhibit LPS-induced secretion of TNF-{alpha} and IL-8. Black-Right-Pointing-Pointer Quince peel polyphenols augment LPS-induced secretion of IL-10 and IL-6. Black-Right-Pointing-Pointer Quince peel polyphenols-mediated inhibition of LPS-induced secretion of TNF-{alpha} is partially mediated by IL-6. Black-Right-Pointing-Pointer The anti-inflammatory effects of quince polyphenols pass through NF-{kappa}B, p38MAPK and Akt inhibition. -- Abstract: Chronic inflammation is a hallmark of several pathologies, such as rheumatoid arthritis, gastritis, inflammatory bowel disease, atherosclerosis and cancer. A wide range of anti-inflammatory chemicals have been used to treat such diseases while presenting high toxicity and numerous side effects. Here, we report the anti-inflammatory effect of a non-toxic, cost-effective natural agent, polyphenolic extract from the Tunisian quince Cydonia oblonga Miller. Lipopolysaccharide (LPS) treatment of human THP-1-derived macrophages induced the secretion of high levels of the pro-inflammatory cytokine TNF-{alpha} and the chemokine IL-8, which was inhibited by quince peel polyphenolic extract in a dose-dependent manner. Concomitantly, quince polyphenols enhanced the level of the anti-inflammatory cytokine IL-10 secreted by LPS-treated macrophages. We further demonstrated that the unexpected increase in IL-6 secretion that occurred when quince polyphenols were associated with LPS treatment was partially responsible for the polyphenols-mediated inhibition of TNF-{alpha} secretion. Biochemical analysis showed that quince polyphenols extract inhibited the LPS-mediated activation of three major cellular pro-inflammatory effectors, nuclear factor-kappa B (NF-{kappa}B), p38MAPK and Akt. Overall, our data indicate that quince peel polyphenolic extract induces a potent anti-inflammatory effect that may prove useful for the treatment of inflammatory diseases and that a quince

Regulation of development and function of different T cell subtypes by Rel/NF-{kappa}B family members

Energy Technology Data Exchange (ETDEWEB)

Vallabhapurapu, S.

2004-09-01

This study reveals the requirement of distinct members of the Rel/NF-{kappa}B family in both hematopoietic and non-hematopoietic cells for the development of thymic NKT cells. Activation of NF-{kappa}B via the classical I{kappa}B{alpha}-regulated pathway is required within the NKT precursors for their efficient maturation from NK1.1{sup -} precursors to mature NK1.1{sup +} NKT cells. The Rel/NF-{kappa}B family member RelB, on the other hand, is required in thymic stromal cells for the generation of very early NK1.1{sup -} precursors. NF-{kappa}B-inducing kinase (NIK) has also been shown to be required in thymic stromal cells for NKT cell development and this study demonstrates that NIK specifically regulates both constitutive and signal-induced DNA binding of RelB, but not RelA. Moreover, NIK-induced DNA binding of RelB depends on the processing of inhibitory p100 to p52, revealing an alternate pathway of NF-{kappa}B induction. Thus, Rel/NF-{kappa}B complexes activated by the classical I{kappa}B{alpha}-regulated pathway in NKT precursors and an alternate NIK/p100/RelB pathway in thymic stromal cells regulate different stages of NKT cell development. (orig.)

MAML1 regulates cell viability via the NF-{kappa}B pathway in cervical cancer cell lines

Energy Technology Data Exchange (ETDEWEB)

Kuncharin, Yanin [Medical Microbiology Interdisciplinary Program, Graduate School, Chulalongkorn University, Payathai Road, Pathumwan, Bangkok 10330 (Thailand); Sangphech, Naunpun [Biotechnology Program, Faculty of Science, Chulalongkorn University, Payathai Road, Pathumwan, Bangkok 10330 (Thailand); Kueanjinda, Patipark [Medical Microbiology Interdisciplinary Program, Graduate School, Chulalongkorn University, Payathai Road, Pathumwan, Bangkok 10330 (Thailand); Bhattarakosol, Parvapan [Medical Microbiology Interdisciplinary Program, Graduate School, Chulalongkorn University, Payathai Road, Pathumwan, Bangkok 10330 (Thailand); Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Payathai Road, Pathumwan, Bangkok 10330 (Thailand); Palaga, Tanapat, E-mail: tanapat.p@chula.ac.th [Department of Microbiology, Faculty of Science, Chulalongkorn University, Payathai Road, Pathumwan, Bangkok 10330 (Thailand)

2011-08-01

DN-MAML exhibited loss of phospho-I{kappa}B{alpha}, decreased total I{kappa}B{alpha} and nuclear localization of NF-{kappa}B p65, which suggests that the NF-{kappa}B pathway is hyperactivated. Furthermore, increased level of cleaved Notch1 was detected when DN-MAML was expressed. When DN-MAML-overexpressing cells were treated with GSI, significantly decreased cell viability was observed, indicating that inhibition of Notch signaling using GSI treatment and DN-MAML expression negatively affects cell viability. Taken together, targeting Notch signaling using DN-MAML and GSI treatment may present a novel method to control cell viability in cervical cancer cells.

An evaluation of nuclear factor kappa B expression in colorectal carcinoma: An analysis of 50 cases

Directory of Open Access Journals (Sweden)

Nikhil Moorchung

2014-01-01

Conclusions: It is likely that NFkB is an important factor in the pathogenesis of CRC. Further studies including therapeutic intervention using strategies which prevent activation of NFkB in colorectal carcinoma patients will tell if we could alter the course of the disease favorably.

Human factor analysis and preventive countermeasures in nuclear power plant

International Nuclear Information System (INIS)

Li Ye

2010-01-01

Based on the human error analysis theory and the characteristics of maintenance in a nuclear power plant, human factors of maintenance in NPP are divided into three different areas: human, technology, and organization. Which is defined as individual factors, including psychological factors, physiological characteristics, health status, level of knowledge and interpersonal skills; The technical factors including technology, equipment, tools, working order, etc.; The organizational factors including management, information exchange, education, working environment, team building and leadership management,etc The analysis found that organizational factors can directly or indirectly affect the behavior of staff and technical factors, is the most basic human error factor. Based on this nuclear power plant to reduce human error and measures the response. (authors)

DMPD: NF-kappaB activation by reactive oxygen species: fifteen years later. [Dynamic Macrophage Pathway CSML Database

Lifescience Database Archive (English)

Full Text Available 16723122 NF-kappaB activation by reactive oxygen species: fifteen years later. Gloi...svg) (.html) (.csml) Show NF-kappaB activation by reactive oxygen species: fifteen years later. PubmedID 167...23122 Title NF-kappaB activation by reactive oxygen species: fifteen years later.

Cationization of kappa- and iota-carrageenan--Characterization and properties of amphoteric polysaccharides.

Science.gov (United States)

Barahona, Tamara; Prado, Héctor J; Bonelli, Pablo R; Cukierman, Ana L; Fissore, Eliana L; Gerschenson, Lia N; Matulewicz, María C

2015-08-01

Commercial kappa- and iota carrageenans were cationized with 3-chloro-2-hydroxypropyltrimethylammonium chloride in aqueous sodium hydroxide solution. For kappa-carrageenan three derivatives with different degrees of substitution were obtained. Native and amphoteric kappa-carrageenans were characterized by NMR and infrared spectroscopy, scanning electron and atomic force microscopy; methanolysis products were studied by electrospray ionization mass spectrometry. Young moduli and the strain at break of films, differential scanning calorimetry, rheological and flocculation behavior were also evaluated; the native and the amphoteric derivatives showed different and interesting properties. Cationization of iota-carrageenan was more difficult, indicating as it was previously observed for agarose, that substitution starts preferentially on the 2-position of 3,6-anhydrogalactose residues; in iota-carrageenan this latter unit is sulfated. Copyright © 2015 Elsevier Ltd. All rights reserved.

Nuclear modification factor using Tsallis non-extensive statistics

Energy Technology Data Exchange (ETDEWEB)

Tripathy, Sushanta; Garg, Prakhar; Kumar, Prateek; Sahoo, Raghunath [Indian Institute of Technology Indore, Discipline of Physics, School of Basic Sciences, Simrol (India); Bhattacharyya, Trambak; Cleymans, Jean [University of Cape Town, UCT-CERN Research Centre and Department of Physics, Rondebosch (South Africa)

2016-09-15

The nuclear modification factor is derived using Tsallis non-extensive statistics in relaxation time approximation. The variation of the nuclear modification factor with transverse momentum for different values of the non-extensive parameter, q, is also observed. The experimental data from RHIC and LHC are analysed in the framework of Tsallis non-extensive statistics in a relaxation time approximation. It is shown that the proposed approach explains the R{sub AA} of all particles over a wide range of transverse momentum but does not seem to describe the rise in R{sub AA} at very high transverse momenta. (orig.)

Geologic factors in nuclear waste disposal

International Nuclear Information System (INIS)

Towse, D.

1978-07-01

The study of geosciences and their relation to nuclear waste disposal and management entails analyzing the hydrology, chemistry, and geometry of the nuclear waste migration process. Hydrologic effects are determined by analyzing the porosity and permeability (natural and induced) of rock as well as pressures and gradients, dispersion, and aquifer length of the system. Chemistry parameters include radionuclide retardation factors and waste dissolution rate. Geometric parameters (i.e., parameters with dimension) evaluated include repository layer thickness, fracture zone area, tunnel length, and aquifer length. The above parameters act as natural barriers or controls to nuclear waste migration, and are evaluated in three potential geologic media: salt, shale, and crystalline rock deposits. Parametric values are assigned that correspond to many existing situations. These values, in addition to other important inputs, are lumped as a hydrology input into a computer simulation program used to model and calculate nuclear waste migration from the repository to the biosphere, and potential individual and population dose and radiation effects. These results are preliminary and show trends only; they do not represent an actual risk analysis

US Nuclear Regulatory Commission Human Factors Program Plan. Revision 1

International Nuclear Information System (INIS)

1984-09-01

The purpose of the NRC Human Factors Program Plan (NUREG-0985) is to ensure that proper consideration is given to human factors in the design, operation, and maintenance of nuclear facilities. This revised plan addresses nuclear power plants (NPPs) and describes (1) the technical assistance and research activities planned to provide the technical bases for the resolution of the remaining human factors related tasks described in NUREG-0660, THE NRC Action Plan developed as a result of the TMI-2 Accident, and NUREG-0737, Clarification of TMI Action Plan Requirements; (2) the additional human factors efforts identified during implementation of the Action Plan that should receive NRC attention; (3) conduct of developmental activities specified in NUREG-0985 during FY-83; and (4) the impact of Section 306 of the Nuclear Waste Policy Act of 1982, PL 97-425. The plan represents a systematic and comprehensive approach for addressing human factors concerns important to NPP safety in the FY-84 through FY-86 time frame

Human factors methods in DOE nuclear facilities

International Nuclear Information System (INIS)

Bennett, C.T.; Banks, W.W.; Waters, R.J.

1993-01-01

The US Department of Energy (DOE) is in the process of developing a series of guidelines for the use of human factors standards, procedures, and methods to be used in nuclear facilities. This paper discusses the philosophy and process being used to develop a DOE human factors methods handbook to be used during the design cycle. The following sections will discuss: (1) basic justification for the project; (2) human factors design objectives and goals; and (3) role of human factors engineering (HFE) in the design cycle

NMR study on the network structure of a mixed gel of kappa and iota carrageenans.

Science.gov (United States)

Hu, Bingjie; Du, Lei; Matsukawa, Shingo

2016-10-05

The temperature dependencies of the (1)H T2 and diffusion coefficient (D) of a mixed solution of kappa-carrageenan and iota-carrageenan were measured by NMR. Rheological and NMR measurements suggested an exponential formation of rigid aggregates of kappa-carrageenan and a gradual formation of fine aggregates of iota-carrageenan during two step increases of G'. The results also suggested that longer carrageenan chains are preferentially involved in aggregation, thus resulting in a decrease in the average Mw of solute carrageenans. The results of diffusion measurements for poly(ethylene oxide) (PEO) suggested that kappa-carrageenan formed thick aggregates that decreased hindrance to PEO diffusion by decreasing the solute kappa-carrageenan concentration in the voids of the aggregated chains, and that iota-carrageenan formed fine aggregates that decreased the solute iota-carrageenan concentration less. DPEO in a mixed solution of kappa-carrageenan and iota-carrageenan suggested two possibilities for the microscopic network structure: an interpenetrating network structure, or micro-phase separation. Copyright © 2016. Published by Elsevier Ltd.

Inhibitor of apoptosis (IAP) proteins in regulation of inflammation and innate immunity

DEFF Research Database (Denmark)

Damgaard, Rune B; Gyrd-Hansen, Mads

2011-01-01

, and XIAP facilitate ubiquitin-dependent signaling activated by these PRRs and mediate activation of nuclear factor-kappa B (NF-kappaB) transcription factors as well as the MAP kinases p38 and JNK. Here, we review the current understanding of IAP-mediated PRR signaling and how IAP proteins might present...

Reduced skeletal muscle inhibitor of kappaB beta content is associated with insulin resistance in subjects with type 2 diabetes: reversal by exercise training.

Science.gov (United States)

Sriwijitkamol, Apiradee; Christ-Roberts, Christine; Berria, Rachele; Eagan, Phyllis; Pratipanawatr, Thongchai; DeFronzo, Ralph A; Mandarino, Lawrence J; Musi, Nicolas

2006-03-01

Skeletal muscle insulin resistance plays a key role in the pathogenesis of type 2 diabetes. It recently has been hypothesized that excessive activity of the inhibitor of kappaB (IkappaB)/nuclear factor kappaB (NFkappaB) inflammatory pathway is a mechanism underlying skeletal muscle insulin resistance. However, it is not known whether IkappaB/NFkappaB signaling in muscle from subjects with type 2 diabetes is abnormal. We studied IkappaB/NFkappaB signaling in vastus lateralis muscle from six subjects with type 2 diabetes and eight matched control subjects. Muscle from type 2 diabetic subjects was characterized by a 60% decrease in IkappaB beta protein abundance, an indicator of increased activation of the IkappaB/NFkappaB pathway. IkappaB beta abundance directly correlated with insulin-mediated glucose disposal (Rd) during a hyperinsulinemic (40 mU x m(-2) x min(-1))-euglycemic clamp (r = 0.63, P = 0.01), indicating that increased IkappaB/NFkappaB pathway activity is associated with muscle insulin resistance. We also investigated whether reversal of this abnormality could be a mechanism by which training improves insulin sensitivity. In control subjects, 8 weeks of aerobic exercise training caused a 50% increase in both IkappaB alpha and IkappaB beta protein. In subjects with type 2 diabetes, training increased IkappaB alpha and IkappaB beta protein to levels comparable with that of control subjects, and these increments were accompanied by a 40% decrease in tumor necrosis factor alpha muscle content and a 37% increase in insulin-stimulated glucose disposal. In summary, subjects with type 2 diabetes have reduced IkappaB protein abundance in muscle, suggesting excessive activity of the IkappaB/NFkappaB pathway. Moreover, this abnormality is reversed by exercise training.

Nuclear modification factor for J/ψ production in nucleus-nucleus collisions

International Nuclear Information System (INIS)

Xu Xiaoming; Zhou Jie

2011-01-01

The STAR Collaboration has offered an eminent nuclear modification factor of J/ψ at high p T and midrapidity produced in Cu-Cu collisions at √ s NN= 200 GeV. Recalling a prediction, we can understand that the feature of high-p T nuclear modification factor is related to cc produced by 2 → 1 and 2 → 2 partonic processes in deconfined matter, particularly in the prethermal stage and to the recombination of c and c-bar. The nuclear modification factor at high p T is sensitive to the earliest form of deconfined matter that does not have a temperature.(authors)

Supersensitive Kappa Opioid Receptors Promotes Ethanol Withdrawal-Related Behaviors and Reduce Dopamine Signaling in the Nucleus Accumbens.

Science.gov (United States)

Rose, Jamie H; Karkhanis, Anushree N; Chen, Rong; Gioia, Dominic; Lopez, Marcelo F; Becker, Howard C; McCool, Brian A; Jones, Sara R

2016-05-01

Chronic ethanol exposure reduces dopamine transmission in the nucleus accumbens, which may contribute to the negative affective symptoms associated with ethanol withdrawal. Kappa opioid receptors have been implicated in withdrawal-induced excessive drinking and anxiety-like behaviors and are known to inhibit dopamine release in the nucleus accumbens. The effects of chronic ethanol exposure on kappa opioid receptor-mediated changes in dopamine transmission at the level of the dopamine terminal and withdrawal-related behaviors were examined. Five weeks of chronic intermittent ethanol exposure in male C57BL/6 mice were used to examine the role of kappa opioid receptors in chronic ethanol-induced increases in ethanol intake and marble burying, a measure of anxiety/compulsive-like behavior. Drinking and marble burying were evaluated before and after chronic intermittent ethanol exposure, with and without kappa opioid receptor blockade by nor-binaltorphimine (10mg/kg i.p.). Functional alterations in kappa opioid receptors were assessed using fast scan cyclic voltammetry in brain slices containing the nucleus accumbens. Chronic intermittent ethanol-exposed mice showed increased ethanol drinking and marble burying compared with controls, which was attenuated with kappa opioid receptor blockade. Chronic intermittent ethanol-induced increases in behavior were replicated with kappa opioid receptor activation in naïve mice. Fast scan cyclic voltammetry revealed that chronic intermittent ethanol reduced accumbal dopamine release and increased uptake rates, promoting a hypodopaminergic state of this region. Kappa opioid receptor activation with U50,488H concentration-dependently decreased dopamine release in both groups; however, this effect was greater in chronic intermittent ethanol-treated mice, indicating kappa opioid receptor supersensitivity in this group. These data suggest that the chronic intermittent ethanol-induced increase in ethanol intake and anxiety

Commutators of Littlewood-Paley gκ∗$g_{\\kappa}^{*} $-functions on non-homogeneous metric measure spaces

Directory of Open Access Journals (Sweden)

Lu Guanghui

2017-11-01

Full Text Available The main purpose of this paper is to prove that the boundedness of the commutator Mκ,b∗$\\mathcal{M}_{\\kappa,b}^{*} $ generated by the Littlewood-Paley operator Mκ∗$\\mathcal{M}_{\\kappa}^{*} $ and RBMO (μ function on non-homogeneous metric measure spaces satisfying the upper doubling and the geometrically doubling conditions. Under the assumption that the kernel of Mκ∗$\\mathcal{M}_{\\kappa}^{*} $ satisfies a certain Hörmander-type condition, the authors prove that Mκ,b∗$\\mathcal{M}_{\\kappa,b}^{*} $ is bounded on Lebesgue spaces Lp(μ for 1 < p < ∞, bounded from the space L log L(μ to the weak Lebesgue space L1,∞(μ, and is bounded from the atomic Hardy spaces H1(μ to the weak Lebesgue spaces L1,∞(μ.

Research of human factor in nuclear power plants

International Nuclear Information System (INIS)

Nopp, I.

1983-01-01

The question is discussed of the study of the human factor with regard to the reliability of nuclear power plant operation. The reliability of the human factor is the result of the functional fitness, motivation, working conditions and working regime of personnel. (J.B.)

Human factor engineering applied to nuclear power plant design

International Nuclear Information System (INIS)

Manrique, A.; Valdivia, J.C.; Jimenez, A.

2001-01-01

For the design and construction of new nuclear power plants as well as for maintenance and operation of the existing ones new man-machine interface designs and modifications are been produced. For these new designs Human Factor Engineering must be applied the same as for any other traditional engineering discipline. Advantages of implementing adequate Human Factor Engineering techniques in the design of nuclear reactors have become not only a fact recognized by the majority of engineers and operators but also an explicit requirement regulated and mandatory for the new designs of the so called advanced reactors. Additionally, the big saving achieved by a nuclear power plant having an operating methodology which significantly decreases the risk of operating errors makes it necessary and almost vital its implementation. The first step for this is preparing a plan to incorporate all the Human Factor Engineering principles and developing an integral design of the Instrumentation and Control and Man-machine interface systems. (author)

Observer variability in the assessment of type and dysplasia of colorectal adenomas, analyzed using kappa statistics

DEFF Research Database (Denmark)

Jensen, P; Krogsgaard, M R; Christiansen, J

1995-01-01

. The kappa values for Observer A vs. B and Observer C vs. B were 0.3480 and 0.3770, respectively (both type and dysplasia). Values for type were better than for dysplasia, but agreement was only fair to moderate. CONCLUSION: The interobserver agreement was moderate to almost perfect, but the intraobserver...... agreement was only fair to moderate. A simpler classification system or a centralization of assessments would probably increase kappa values....... of adenomas were assessed twice by three experienced pathologists, with an interval of two months. Results were analyzed using kappa statistics. RESULTS: For agreement between first and second assessment (both type and grade of dysplasia), kappa values for the three specialists were 0.5345, 0.9022, and 0...

Alfven waves in dusty plasmas with plasma particles described by anisotropic kappa distributions

Energy Technology Data Exchange (ETDEWEB)

Galvao, R. A.; Ziebell, L. F. [Instituto de Fisica, Universidade Federal do Rio Grande do Sul, Caixa Postal 15051, CEP: 91501-970, Porto Alegre, Rio Grande do Sul (Brazil); Gaelzer, R. [Instituto de Fisica e Matematica, Universidade Federal de Pelotas, Caixa Postal 354-Campus UFPel, CEP: 96010-900 Pelotas, Rio Grande do Sul (Brazil); Juli, M. C. de [Centro de Radio-Astronomia e Astrofisica Mackenzie-CRAAM, Universidade Presbiteriana Mackenzie, Rua da Consolacao 896, CEP: 01302-907 Sao Paulo, Sao Paulo (Brazil)

2012-12-15

We utilize a kinetic description to study the dispersion relation of Alfven waves propagating parallelly to the ambient magnetic field in a dusty plasma, taking into account the fluctuation of the charge of the dust particles, which is due to inelastic collisions with electrons and ions. We consider a plasma in which the velocity distribution functions of the plasma particles are modelled as anisotropic kappa distributions, study the dispersion relation for several combinations of the parameters {kappa}{sub Parallel-To} and {kappa}{sub Up-Tack }, and emphasize the effect of the anisotropy of the distributions on the mode coupling which occurs in a dusty plasma, between waves in the branch of circularly polarized waves and waves in the whistler branch.

Behavioral meaningful opioidergic stimulation activates kappa receptor gene expression

Directory of Open Access Journals (Sweden)

E. Teodorov

2012-10-01

Full Text Available The periaqueductal gray (PAG has been reported to be a location for opioid regulation of pain and a potential site for behavioral selection in females. Opioid-mediated behavioral and physiological responses differ according to the activity of opioid receptor subtypes. The present study investigated the effects of the peripheral injection of the kappa-opioid receptor agonist U69593 into the dorsal subcutaneous region of animals on maternal behavior and on Oprk1 gene activity in the PAG of female rats. Female Wistar rats weighing 200-250 g at the beginning of the study were randomly divided into 2 groups for maternal behavior and gene expression experiments. On day 5, pups were removed at 7:00 am and placed in another home cage that was distant from their mother. Thirty minutes after removing the pups, the dams were treated with U69593 (0.15 mg/kg, sc or 0.9% saline (up to 1 mL/kg and after 30 min were evaluated in the maternal behavior test. Latencies in seconds for pup retrieval, grouping, crouching, and full maternal behavior were scored. The results showed that U69593 administration inhibited maternal behavior (P < 0.05 because a lower percentage of kappa group dams showed retrieval of first pup, retrieving all pups, grouping, crouching and displaying full maternal behavior compared to the saline group. Opioid gene expression was evaluated using real-time reverse-transcription polymerase chain reaction (RT-PCR. A single injection of U69593 increased Oprk1 PAG expression in both virgin (P < 0.05 and lactating female rats (P < 0.01, with no significant effect on Oprm1 or Oprd1 gene activity. Thus, the expression of kappa-opioid receptors in the PAG may be modulated by single opioid receptor stimulation and behavioral meaningful opioidergic transmission in the adult female might occur simultaneously to specific changes in gene expression of kappa-opioid receptor subtype. This is yet another alert for the complex role of the opioid system in

Nuclear energy - stabilising factor in the world economy

International Nuclear Information System (INIS)

Legassov, V.; Feoktistov, L.; Kouzmine, I.

1986-01-01

One of the most important factors for international stability is the development of the economy, reducing the risk of local armed conflicts which could escalate into world-wide nuclear war. Economic progress which plays such a vital part is in turn heavily dependent on energy supplies. The article takes a brief look at the role of nuclear power in this context. (B.M.S.)

Human Factors in Nuclear Reactor Accidents

International Nuclear Information System (INIS)

Mustafa, M.E.

2016-01-01

While many people would blame nature for the disaster of the “Fukushima Daiichi” accident, experts considered this accident to be also a human-induced disaster. This confirmed the importance of human errors which have been getting a growing interest in the nuclear field after the Three Mile Island accident. Personnel play an important role in design, operation, maintenance, planning, and management. The interface between machine and man is known as a human factor. In the present work, the human factors that have to be considered were discussed. The effect of the control room configuration and equipment design effect on the human behavior was also discussed. Precise reviewing of person’s qualifications and experience was focused. Insufficient training has been a major cause of human error in the nuclear field. The effective training issues were introduced. Avoiding complicated operational processes and non responsive management systems was stressed. Distinguishing between the procedures for normal and emergency operations was emphasised. It was stated that human error during maintenance and testing activities could cause a serious accident. This is because safety systems do not cover much more risk probabilities in the maintenance and testing activities like they do in the normal operation. In nuclear industry, the need for a classification and identification of human errors has been well recognised. As a result of this, human reliability must be assessed. These errors are analyzed by a probabilistic safety assessment which deals with errors in reading, listening and implementing procedures but not with cognitive errors. Much efforts must be accomplished to consider cognitive errors in the probabilistic safety assessment. The ways of collecting human factor data were surveyed. The methods for identifying safe designs, helping decision makers to predict how proposed or current policies will affect safety, and comprehensive understanding of the relationship

Review of EPRI Nuclear Human Factors Program

International Nuclear Information System (INIS)

Hanes, L.F.; O'Brien, J.F.

1996-01-01

The Electric Power Research Institute (EPRI) Human Factors Program, which is part of the EPRI Nuclear Power Group, was established in 1975. Over the years, the Program has changed emphasis based on the shifting priorities and needs of the commercial nuclear power industry. The Program has produced many important products that provide significant safety and economic benefits for EPRI member utilities. This presentation will provide a brief history of the Program and products. Current projects and products that have been released recently will be mentioned

Protective effect of nuclear factor E2-related factor 2 on inflammatory cytokine response to brominated diphenyl ether-47 in the HTR-8/SVneo human first trimester extravillous trophoblast cell line

International Nuclear Information System (INIS)

Park, Hae-Ryung; Loch-Caruso, Rita

2014-01-01

Polybrominated diphenyl ethers (PBDEs) are widely used flame retardants, and BDE-47 is a prevalent PBDE congener detected in human tissues. Exposure to PBDEs has been linked to adverse pregnancy outcomes in humans. Although the underlying mechanisms of adverse birth outcomes are poorly understood, critical roles for oxidative stress and inflammation are implicated. The present study investigated antioxidant responses in a human extravillous trophoblast cell line, HTR-8/SVneo, and examined the role of nuclear factor E2-related factor 2 (Nrf2), an antioxidative transcription factor, in BDE-47-induced inflammatory responses in the cells. Treatment of HTR-8/SVneo cells with 5, 10, 15, and 20 μM BDE-47 for 24 h increased intracellular glutathione (GSH) levels compared to solvent control. Treatment of HTR-8/SVneo cells with 20 μM BDE-47 for 24 h induced the antioxidant response element (ARE) activity, indicating Nrf2 transactivation by BDE-47 treatment, and resulted in differential expression of redox-sensitive genes compared to solvent control. Pretreatment with tert-butyl hydroquinone (tBHQ) or sulforaphane, known Nrf2 inducers, reduced BDE-47-stimulated IL-6 release with increased ARE reporter activity, reduced nuclear factor kappa B (NF-κB) reporter activity, increased GSH production, and stimulated expression of antioxidant genes compared to non-Nrf2 inducer pretreated groups, suggesting that Nrf2 may play a protective role against BDE-47-mediated inflammatory responses in HTR-8/SVneo cells. These results suggest that Nrf2 activation significantly attenuated BDE-47-induced IL-6 release by augmentation of cellular antioxidative system via upregulation of Nrf2 signaling pathways, and that Nrf2 induction may be a potential therapeutic target to reduce adverse pregnancy outcomes associated with toxicant-induced oxidative stress and inflammation. - Highlights: • BDE-47 stimulated ARE reporter activity and GSH production. • BDE-47 resulted in differential

Protective effect of nuclear factor E2-related factor 2 on inflammatory cytokine response to brominated diphenyl ether-47 in the HTR-8/SVneo human first trimester extravillous trophoblast cell line

Energy Technology Data Exchange (ETDEWEB)

Park, Hae-Ryung, E-mail: heaven@umich.edu; Loch-Caruso, Rita

2014-11-15

Polybrominated diphenyl ethers (PBDEs) are widely used flame retardants, and BDE-47 is a prevalent PBDE congener detected in human tissues. Exposure to PBDEs has been linked to adverse pregnancy outcomes in humans. Although the underlying mechanisms of adverse birth outcomes are poorly understood, critical roles for oxidative stress and inflammation are implicated. The present study investigated antioxidant responses in a human extravillous trophoblast cell line, HTR-8/SVneo, and examined the role of nuclear factor E2-related factor 2 (Nrf2), an antioxidative transcription factor, in BDE-47-induced inflammatory responses in the cells. Treatment of HTR-8/SVneo cells with 5, 10, 15, and 20 μM BDE-47 for 24 h increased intracellular glutathione (GSH) levels compared to solvent control. Treatment of HTR-8/SVneo cells with 20 μM BDE-47 for 24 h induced the antioxidant response element (ARE) activity, indicating Nrf2 transactivation by BDE-47 treatment, and resulted in differential expression of redox-sensitive genes compared to solvent control. Pretreatment with tert-butyl hydroquinone (tBHQ) or sulforaphane, known Nrf2 inducers, reduced BDE-47-stimulated IL-6 release with increased ARE reporter activity, reduced nuclear factor kappa B (NF-κB) reporter activity, increased GSH production, and stimulated expression of antioxidant genes compared to non-Nrf2 inducer pretreated groups, suggesting that Nrf2 may play a protective role against BDE-47-mediated inflammatory responses in HTR-8/SVneo cells. These results suggest that Nrf2 activation significantly attenuated BDE-47-induced IL-6 release by augmentation of cellular antioxidative system via upregulation of Nrf2 signaling pathways, and that Nrf2 induction may be a potential therapeutic target to reduce adverse pregnancy outcomes associated with toxicant-induced oxidative stress and inflammation. - Highlights: • BDE-47 stimulated ARE reporter activity and GSH production. • BDE-47 resulted in differential

Adaptive evolution of relish, a Drosophila NF-kappaB/IkappaB protein.

OpenAIRE

Begun, D J; Whitley, P

2000-01-01

NF-kappaB and IkappaB proteins have central roles in regulation of inflammation and innate immunity in mammals. Homologues of these proteins also play an important role in regulation of the Drosophila immune response. Here we present a molecular population genetic analysis of Relish, a Drosophila NF-kappaB/IkappaB protein, in Drosophila simulans and D. melanogaster. We find strong evidence for adaptive protein evolution in D. simulans, but not in D. melanogaster. The adaptive evolution appear...

Nuclear Regulatory Commission Human Factors Program Plan. Revision 2

International Nuclear Information System (INIS)

1986-04-01

This document is the Second Annual Revision to the NRC Human Factors Program Plan. The first edition was published in August 1983. Revision 1 was published in July of 1984. Purpose of the NRC Human Factors Program is to ensure that proper consideration is given to human factors in the design and operation of nuclear power plants. This document describes the plans of the Office of Nuclear Reactor Regulation to address high priority human factors concerns of importance to reactor safety in FY 1986 and FY 1987. Revision 2 of the plan incorporates recent Commission decisions and policies bearing on the human factors aspects of reactor safety regulation. With a few exceptions, the principal changes from prior editions reflect a shift from developing new requirements to staff evaluation of industry progress in resolving human factors issues. The plan addresses seven major program elements: (1) Training, (2) Licensing Examinations, (3) Procedures, (4) Man-Machine Interface, (5) Staffing and Qualifications, (6) Management and Organization, and (7) Human Performance

Personality Factors and Nuclear Power Plant Operators: Initial License Success

Science.gov (United States)

DeVita-Cochrane, Cynthia

Commercial nuclear power utilities are under pressure to effectively recruit and retain licensed reactor operators in light of poor candidate training completion rates and recent candidate failures on the Nuclear Regulatory Commission (NRC) license exam. One candidate failure can cost a utility over $400,000, making the successful licensing of new operators a critical path to operational excellence. This study was designed to discover if the NEO-PI-3, a 5-factor measure of personality, could improve selection in nuclear utilities by identifying personality factors that predict license candidate success. Two large U.S. commercial nuclear power corporations provided potential participant contact information and candidate results on the 2014 NRC exam from their nuclear power units nation-wide. License candidates who participated (n = 75) completed the NEO-PI-3 personality test and results were compared to 3 outcomes on the NRC exam: written exam, simulated operating exam, and overall exam result. Significant correlations were found between several personality factors and both written and operating exam outcomes on the NRC exam. Further, a regression analysis indicated that personality factors, particularly Conscientiousness, predicted simulated operating exam scores. The results of this study may be used to support the use of the NEO-PI-3 to improve operator selection as an addition to the current selection protocol. Positive social change implications from this study include support for the use of a personality measure by utilities to improve their return-on-investment in candidates and by individual candidates to avoid career failures. The results of this study may also positively impact the public by supporting the safe and reliable operation of commercial nuclear power utilities in the United States.

Quality management in the nuclear industry: the human factor

International Nuclear Information System (INIS)

1990-01-01

In the nuclear industry it is vital to understand the 'human factor' with regard to plant performance and plant safety. A proper management system ensures that personnel perform their duties correctly. 'Quality Management in the Nuclear Industry: the Human Factor', was a conference organized by the Institution of Mechanical Engineers in October 1990. The conference covered a wide range of topics on an international level including: standards, licensing and regulatory procedures; selection assessment and training of personnel; feedback from experience of good practice and of deviations; management and support of personnel performance; modelling and evaluation of human factors. The papers presented at the conference are contained in this volume. All twenty papers are indexed separately. (author)

Salidroside attenuates inflammatory responses by suppressing nuclear factor-κB and mitogen activated protein kinases activation in lipopolysaccharide-induced mastitis in mice.

Science.gov (United States)

Li, Depeng; Fu, Yunhe; Zhang, Wen; Su, Gaoli; Liu, Bo; Guo, Mengyao; Li, Fengyang; Liang, Dejie; Liu, Zhicheng; Zhang, Xichen; Cao, Yongguo; Zhang, Naisheng; Yang, Zhengtao

2013-01-01

Mastitis is defined as inflammation of the mammary gland in domestic dairy animals and humans. Salidroside, a major component isolated from Rhodiola rosea L., has potent anti-inflammatory properties, but whether it can be used in mastitis treatment has not yet been investigated. The aim of this study was to assess the protective effects of salidroside against lipopolysaccharide (LPS)-induced mastitis in mice and the mechanism of action. We used a mouse mastitis model in which mammary gland inflammation was induced by LPS challenge. Salidroside administered 1 h before LPS infusion significantly attenuated inflammatory cell infiltration, reduced the activity of myeloperoxidase in mammary tissue, and decreased the concentration of tumor necrosis factor-α, interleukin (IL)-1β, and IL-6 in a dose-dependent manner. Further studies revealed that salidroside down-regulated phosphorylation of LPS-induced nuclear transcription factor-kappaB (NF-κB) p65 and inhibitor of NF-κB α (IκBα) in the NF-κB signal pathway, and suppressed phosphorylation of p38, extracellular signal-regulated kinase (ERK) and c-jun NH(2)-terminal kinase (JNK) in MAPKs signal pathways. This study demonstrates that salidroside is an effective suppressor of inflammation and may be a candidate for the prophylaxis of mastitis.

Critical human-factors issues in nuclear-power regulation and a recommended comprehensive human-factors long-range plan. Executive summary

International Nuclear Information System (INIS)

Hopkins, C.O.; Snyder, H.L.; Price, H.E.; Hornick, R.J.; Mackie, R.R.; Smillie, R.J.; Sugarman, R.C.

1982-08-01

This comprehensive long-range human factors plan for nuclear reactor regulation was developed by a Study Group of the Human Factors Society, Inc. This Study Group was selected by the Executive Council of the Society to provide a balanced, experienced human factors perspective to the applications of human factors scientific and engineering knowledge to nuclear power generation. The report is presented in three volumes. Volume 1 contains an Executive Summary of the 18-month effort and its conclusions. Volume 2 summarizes all known nuclear-related human factors activities, evaluates these activities wherever adequate information is available, and describes the recommended long-range (10-year) plan for human factors in regulation. Volume 3 elaborates upon each of the human factors issues and areas of recommended human factors involvement contained in the plan, and discusses the logic that led to the recommendations

Melatonin Inhibits Androgen Receptor Splice Variant-7 (AR-V7)-Induced Nuclear Factor-Kappa B (NF-κB) Activation and NF-κB Activator-Induced AR-V7 Expression in Prostate Cancer Cells: Potential Implications for the Use of Melatonin in Castration-Resistant Prostate Cancer (CRPC) Therapy.

Science.gov (United States)

Liu, Vincent Wing Sun; Yau, Wing Lung; Tam, Chun Wai; Yao, Kwok-Ming; Shiu, Stephen Yuen Wing

2017-05-31

A major current challenge in the treatment of advanced prostate cancer, which can be initially controlled by medical or surgical castration, is the development of effective, safe, and affordable therapies against progression of the disease to the stage of castration resistance. Here, we showed that in LNCaP and 22Rv1 prostate cancer cells transiently overexpressing androgen receptor splice variant-7 (AR-V7), nuclear factor-kappa B (NF-κB) was activated and could result in up-regulated interleukin ( IL ) -6 gene expression, indicating a positive interaction between AR-V7 expression and activated NF-κB/IL-6 signaling in castration-resistant prostate cancer (CRPC) pathogenesis. Importantly, both AR-V7-induced NF-κB activation and IL-6 gene transcription in LNCaP and 22Rv1 cells could be inhibited by melatonin. Furthermore, stimulation of AR-V7 mRNA expression in LNCaP cells by betulinic acid, a pharmacological NF-κB activator, was reduced by melatonin treatment. Our data support the presence of bi-directional positive interactions between AR-V7 expression and NF-κB activation in CRPC pathogenesis. Of note, melatonin, by inhibiting NF-κB activation via the previously-reported MT₁ receptor-mediated antiproliferative pathway, can disrupt these bi-directional positive interactions between AR-V7 and NF-κB and thereby delay the development of castration resistance in advanced prostate cancer. Apparently, this therapeutic potential of melatonin in advanced prostate cancer/CRPC management is worth translation in the clinic via combined androgen depletion and melatonin repletion.

Melatonin Inhibits Androgen Receptor Splice Variant-7 (AR-V7-Induced Nuclear Factor-Kappa B (NF-κB Activation and NF-κB Activator-Induced AR-V7 Expression in Prostate Cancer Cells: Potential Implications for the Use of Melatonin in Castration-Resistant Prostate Cancer (CRPC Therapy

Directory of Open Access Journals (Sweden)

Vincent Wing Sun Liu

2017-05-01

Full Text Available A major current challenge in the treatment of advanced prostate cancer, which can be initially controlled by medical or surgical castration, is the development of effective, safe, and affordable therapies against progression of the disease to the stage of castration resistance. Here, we showed that in LNCaP and 22Rv1 prostate cancer cells transiently overexpressing androgen receptor splice variant-7 (AR-V7, nuclear factor-kappa B (NF-κB was activated and could result in up-regulated interleukin (IL-6 gene expression, indicating a positive interaction between AR-V7 expression and activated NF-κB/IL-6 signaling in castration-resistant prostate cancer (CRPC pathogenesis. Importantly, both AR-V7-induced NF-κB activation and IL-6 gene transcription in LNCaP and 22Rv1 cells could be inhibited by melatonin. Furthermore, stimulation of AR-V7 mRNA expression in LNCaP cells by betulinic acid, a pharmacological NF-κB activator, was reduced by melatonin treatment. Our data support the presence of bi-directional positive interactions between AR-V7 expression and NF-κB activation in CRPC pathogenesis. Of note, melatonin, by inhibiting NF-κB activation via the previously-reported MT1 receptor-mediated antiproliferative pathway, can disrupt these bi-directional positive interactions between AR-V7 and NF-κB and thereby delay the development of castration resistance in advanced prostate cancer. Apparently, this therapeutic potential of melatonin in advanced prostate cancer/CRPC management is worth translation in the clinic via combined androgen depletion and melatonin repletion.

Human factors guidelines for nuclear power plant applications

International Nuclear Information System (INIS)

Ketchel, J.

1993-01-01

In 1989, Waters et al. reported to the Human Factors Society on developing human factors criteria for a new reactor plant. They correctly indicated that much of the guidance documentation in human factors engineering has derived from MIL-STD-1472 and its antecedents. Guidelines for human-computer interface have sprung primarily from the Smith and Mosier compendium and its source documents. NUREG-0700, which is currently being updated, was developed by the US Nuclear Regulatory Commission (NRC) as a general evaluation guide for inspecting control rooms. In addition, the Electric Power Research Institute, Institute of Nuclear Power Operations, US Department of Energy, the NRC, and others have published a number of specialized documents on a range of subjects. The number of guidelines and standards has grown in the past few years to an impressive number, including those published by international organizations and professional societies. This paper provides an update on current efforts to provide appropriate guidance for the power industry and, perhaps more importantly, offers a perspective on how users should think about using the available materials and what else is needed. The Electric Power Research Institute (EPRI) continues to be one of the principal participants in providing guidance to the utilities. Human factors guidelines is indeed a timely topic, currently of great interest to EPRI's constituents and to designers of new and upgraded nuclear power plants (NPMs) in the Advanced Light Water Reactor and the Instrumentation and Control Upgrade Initiative programs

Human factors design guidelines for maintainability of Department of Energy nuclear facilities

Energy Technology Data Exchange (ETDEWEB)

Bongarra, J.P. Jr.; VanCott, H.P.; Pain, R.F.; Peterson, L.R.; Wallace, R.I.

1985-06-18

Intent of these guidelines is to provide design and design review teams of DOE nuclear facilities with human factors principles to enhance the design and aid in the inspection of DOE nuclear facilities, systems, and equipment. These guidelines are concerned with design features of DOE nuclear facilities which can potentially affect preventive and corrective maintenance of systems within DOE nuclear facilities. Maintenance includes inspecting, checking, troubleshooting, adjusting, replacing, repairing, and servicing activities. Other factors which influence maintainability such as repair and maintenance suport facilities, maintenance information, and various aspects of the environment are also addressed.

Human factors design guidelines for maintainability of Department of Energy nuclear facilities

International Nuclear Information System (INIS)

Bongarra, J.P. Jr.; VanCott, H.P.; Pain, R.F.; Peterson, L.R.; Wallace, R.I.

1985-01-01

Intent of these guidelines is to provide design and design review teams of DOE nuclear facilities with human factors principles to enhance the design and aid in the inspection of DOE nuclear facilities, systems, and equipment. These guidelines are concerned with design features of DOE nuclear facilities which can potentially affect preventive and corrective maintenance of systems within DOE nuclear facilities. Maintenance includes inspecting, checking, troubleshooting, adjusting, replacing, repairing, and servicing activities. Other factors which influence maintainability such as repair and maintenance suport facilities, maintenance information, and various aspects of the environment are also addressed

Measurement of Interobserver Disagreement: Correction of Cohen’s Kappa for Negative Values

Directory of Open Access Journals (Sweden)

Tarald O. Kvålseth

2015-01-01

Full Text Available As measures of interobserver agreement for both nominal and ordinal categories, Cohen’s kappa coefficients appear to be the most widely used with simple and meaningful interpretations. However, for negative coefficient values when (the probability of observed disagreement exceeds chance-expected disagreement, no fixed lower bounds exist for the kappa coefficients and their interpretations are no longer meaningful and may be entirely misleading. In this paper, alternative measures of disagreement (or negative agreement are proposed as simple corrections or modifications of Cohen’s kappa coefficients. The new coefficients have a fixed lower bound of −1 that can be attained irrespective of the marginal distributions. A coefficient is formulated for the case when the classification categories are nominal and a weighted coefficient is proposed for ordinal categories. Besides coefficients for the overall disagreement across categories, disagreement coefficients for individual categories are presented. Statistical inference procedures are developed and numerical examples are provided.

Ion acoustic solitons in a plasma with two-temperature kappa-distributed electrons

Energy Technology Data Exchange (ETDEWEB)

Baluku, T. K.; Hellberg, M. A. [School of Physics, University of KwaZulu-Natal, Private Bag X54001, Durban 4000 (South Africa)

2012-01-15

Existence domains and characteristics of ion acoustic solitons are studied in a two-temperature electron plasma with both electron components being kappa-distributed, as found in Saturn's magnetosphere. As is the case for double-Boltzmann electrons, solitons of both polarities can exist over restricted ranges of fractional hot electron density ratio for this plasma model. Low {kappa} values, which indicate increased suprathermal particles in the tail of the distribution, yield a smaller domain in the parameter space of hot density fraction and normalized soliton velocity (f, M), over which both soliton polarities are supported for a given plasma composition (the coexistence region). For some density ratios that support coexistence, solitons occur even at the lowest (critical) Mach number (i.e., at the acoustic speed), as found recently for a number of other plasma models. Like Maxwellians, low-{kappa} distributions also support positive potential double layers over a narrow range of low fractional cool electron density (<10%).

Adrenergic regulation during acute hepatic infection with Entamoeba histolytica in the hamster: involvement of oxidative stress, Nrf2 and NF-KappaB

Directory of Open Access Journals (Sweden)

Aldaba-Muruato Liseth Rubi

2017-01-01

Full Text Available Oxidative stress and transcriptional pathways of nuclear factor erythroid 2-related factor 2 (Nrf2 and nuclear factor kappa-B (NF-κB are critically involved in the etiopathology of amebic liver abscess (ALA. In this work, we studied the relationship between the adrenergic nervous system and ALA in the hamster. ALA was visible at 12 h of infection. While 6-hydroxidopamine (6-OHDA decreased infection, propranolol (β-adrenergic blocker treatment was associated with less extensive liver damage, and phentolamine treatment (α-adrenergic blocker significantly reduced ALA compared to 6-OHDA and propranolol. Serum enzymatic activities of alanine aminotransferase (ALT and γ-glutamyl transpeptidase (γ-GTP were increased at 12 h post-infection. Chemical denervation and α and β-adrenergic blockers decreased ALT to normal levels, while 6-OHDA and propranolol showed a trend to decrease γ-GTP but phentolamine significantly reduced γ-GTP. Amebic infection increased oxidized glutathione (GSSG and decreased both reduced glutathione (GSH and the GSH/GSSG ratio. Propranolol and 6-OHDA showed a tendency to decrease GSSG. However, GSH, GSSG and GSH/GSSG returned to normal levels with phentolamine. Furthermore, amebic infection increased pNF-κB and interleukin-1β (IL-1β, and showed a tendency to decrease hemoxigenase-1 (HO-1, but not Nrf2. Chemical denervation showed a trend to decrease pNF-κB and IL-1β, and neither Nrf2 nor HO-1 increased significantly. In addition, NF-κB and IL-1β were attenuated by propranolol and phentolamine treatments, although phentolamine showed significant overexpression of Nrf2 and HO-1. This suggests that the adrenergic system may be involved in oxidative stress and in modulation of the Nrf2 and NF-κB pathways during ALA development.

NIRS Characterization of Paper Pulps to Predict Kappa Number

Directory of Open Access Journals (Sweden)

Ana Moral

2015-01-01

Full Text Available Rice is one of the most abundant food crops in the world and its straw stands as an important source of fibres both from an economic and an environmental point of view. Pulp characterization is of special relevance in works involving alternative raw materials, since pulp properties are closely linked to the quality of the final product. One of the analytical techniques that can be used in pulp characterization is near-infrared spectroscopy (NIRS. The use of NIRS has economic and technical advantages over conventional techniques. This paper aims to discuss the convenience of using NIRS to predict Kappa number in rice straw pulps produced under different conditions. We found that the resulting Kappa number can be acceptably estimated by NIRS, as the errors obtained with that method are similar to those found for other techniques.

Key Factors for Nuclear Being Economic after Fukushima

Energy Technology Data Exchange (ETDEWEB)

Roh, Myung Sub; Park, Seo Yeon [KEPCO International Nuclear Graduate School, Ulju (Korea, Republic of)

2012-05-15

It is hard to overstate the importance of electricity to the standard of living and the quality of life in a country. Electricity demand grows with population and with the changing nature, level and composition of economic and social activity. Civilization, industrialization and urbanization are, of course, key factors. It, historically, has shown that each major nuclear accident has caused a re-examination of the risk of nuclear power leading to more stringent safety requirement and higher costs. The Fukushima accident and its likely impact on future nuclear power development are difficult to foresee. The accident was a tragedy for the people affected and seriously undermined public confidence in the safety of nuclear power. A number of countries announced reviews of their programs, some took steps toward phasing out nuclear power entirely, and others reemphasized their expansion plans. The Korean nuclear community is carry out many ambitious projects for last three decades continuously and facing the another challenges relating to the future nuclear power economics and difficulty in financing new investment. In order to meet the above economic objective, it is strongly recommended that great emphasis should be placed on maintaining the nuclear economics without jeopardizing safety such as design simplification, standardization, shortening of construction period, increased availability, etc

Key Factors for Nuclear Being Economic after Fukushima

International Nuclear Information System (INIS)

Roh, Myung Sub; Park, Seo Yeon

2012-01-01

It is hard to overstate the importance of electricity to the standard of living and the quality of life in a country. Electricity demand grows with population and with the changing nature, level and composition of economic and social activity. Civilization, industrialization and urbanization are, of course, key factors. It, historically, has shown that each major nuclear accident has caused a re-examination of the risk of nuclear power leading to more stringent safety requirement and higher costs. The Fukushima accident and its likely impact on future nuclear power development are difficult to foresee. The accident was a tragedy for the people affected and seriously undermined public confidence in the safety of nuclear power. A number of countries announced reviews of their programs, some took steps toward phasing out nuclear power entirely, and others reemphasized their expansion plans. The Korean nuclear community is carry out many ambitious projects for last three decades continuously and facing the another challenges relating to the future nuclear power economics and difficulty in financing new investment. In order to meet the above economic objective, it is strongly recommended that great emphasis should be placed on maintaining the nuclear economics without jeopardizing safety such as design simplification, standardization, shortening of construction period, increased availability, etc

DMPD: Signaling to NF-kappaB by Toll-like receptors. [Dynamic Macrophage Pathway CSML Database

Lifescience Database Archive (English)

Full Text Available l Med. 2007 Nov;13(11):460-9. Epub 2007 Oct 29. (.png) (.svg) (.html) (.csml) Show Signaling to NF-kappaB by Toll-like receptors. Pub...medID 18029230 Title Signaling to NF-kappaB by Toll-like receptors. Authors Kawai T

Human factors aspects of advanced instrumentation in the nuclear industry

International Nuclear Information System (INIS)

Carter, R.J.

1989-01-01

An important consideration in regards to the use of advanced instrumentation in the nuclear industry is the interface between the instrumentation system and the human. A survey, oriented towards identifying the human factors aspects of digital instrumentation, was conducted at a number of United States (US) and Canadian nuclear vendors and utilities. Human factors issues, subsumed under the categories of computer-generated displays, controls, organizational support, training, and related topics were identified. 20 refs., 2 tabs

Induction of cyclooxygenase-2 in macrophages by catalase: role of NF-kappaB and PI3K signaling pathways.

Science.gov (United States)

Jang, Byeong-Churl; Kim, Do-Hyun; Park, Jong-Wook; Kwon, Taeg Kyu; Kim, Sang-Pyo; Song, Dae-Kyu; Park, Jong-Gu; Bae, Jae-Hoon; Mun, Kyo-Chul; Baek, Won-Ki; Suh, Min-Ho; Hla, Timothy; Suh, Seong-Il

2004-04-02

Induction of COX-2 by catalase in smooth muscle cells, endothelial cells, and neuronal cells has been previously reported. However, the mechanism by which catalase up-regulates COX-2 remains poorly understood. In this study, we investigated the effect of catalase on induction of COX-2 in macrophages. The addition of catalase into Raw 264.7 macrophages induced COX-2 expression that was correlated with increased COX-2 transcription and mRNA stability. Catalase also induced activation of NF-kappaB, PI3K, ERKs, p38s, or JNKs. Catalase-induced COX-2 expression was abrogated by treatment of MG-132 (a NF-kappaB inhibitor) or LY294002 (a PI3K inhibitor), but not by treatment of PD98059 (an ERK inhibitor), SB203580 (a p38 inhibitor), or SP600125 (a JNK inhibitor). Moreover, inhibition of PI3K by LY294002 caused partial decrease of catalase-induced COX-2 transcription and steady-state COX-2 transcript levels, but not COX-2 mRNA stability. Together, these results suggest that catalase induces the expression of COX-2 in Raw 264.7 macrophages, and the induction is related with activation of NF-kappaB transcription factor and PI3K signaling pathway.

Factor Analysis and Framework Development for Incorporating Public Trust on Nuclear Safety issues

Energy Technology Data Exchange (ETDEWEB)

Cho, Seongkyung; Lee, Gyebong [The Myongji Univ., Seoul (Korea, Republic of); Lee, Gihyung; Lee, Gyehwi; Jeong, Jina [Korea Institute of Nuclear Safety, Daejeon (Korea, Republic of)

2014-05-15

The Korea Institute of Nuclear Safety (KINS), a regulatory expert organization in charge of nuclear safety in Korea, realized that a more fundamental and systematic analysis of activities is needed to actively meet the greater variety of concerns people have and increase the reliability of the results of regulation. Nuclear safety, a highly specialized field, has previously been discussed primarily from the viewpoint of the engineers who deal with the technology, but now 'public trust in nuclear safety' has to be viewed from the standpoint of the general public and from the socio-cultural perspective. Specific measures must be taken to examine which factors affect public trust and how we can secure and reproduce those factors to gain it. Also, an efficient system for incorporating public trust in nuclear safety must be established. In this study, various case studies were examined to identify the factors that affect public trust in nuclear safety. First, nuclear safety laws and information disclosure systems of major countries were examined by investigating data and conducting in-depth interviews. To explore a public framework concerning nuclear safety, big data of social media were analyzed. Also, Q methodology was used to analyze the risk schemata of the opinion leaders living in areas near nuclear power plants. Several surveys were conducted to analyze the amount of trust the public had in nuclear safety as well as their awareness of nuclear safety issues. Based on these analyses, factors affecting public trust in nuclear safety were extracted, and measures to build systems incorporating public trust in nuclear safety were proposed. This study addresses the public trust in nuclear safety on condition that the safety is ensured technically and mechanically.

Factor Analysis and Framework Development for Incorporating Public Trust on Nuclear Safety issues

International Nuclear Information System (INIS)

Cho, Seongkyung; Lee, Gyebong; Lee, Gihyung; Lee, Gyehwi; Jeong, Jina

2014-01-01

The Korea Institute of Nuclear Safety (KINS), a regulatory expert organization in charge of nuclear safety in Korea, realized that a more fundamental and systematic analysis of activities is needed to actively meet the greater variety of concerns people have and increase the reliability of the results of regulation. Nuclear safety, a highly specialized field, has previously been discussed primarily from the viewpoint of the engineers who deal with the technology, but now 'public trust in nuclear safety' has to be viewed from the standpoint of the general public and from the socio-cultural perspective. Specific measures must be taken to examine which factors affect public trust and how we can secure and reproduce those factors to gain it. Also, an efficient system for incorporating public trust in nuclear safety must be established. In this study, various case studies were examined to identify the factors that affect public trust in nuclear safety. First, nuclear safety laws and information disclosure systems of major countries were examined by investigating data and conducting in-depth interviews. To explore a public framework concerning nuclear safety, big data of social media were analyzed. Also, Q methodology was used to analyze the risk schemata of the opinion leaders living in areas near nuclear power plants. Several surveys were conducted to analyze the amount of trust the public had in nuclear safety as well as their awareness of nuclear safety issues. Based on these analyses, factors affecting public trust in nuclear safety were extracted, and measures to build systems incorporating public trust in nuclear safety were proposed. This study addresses the public trust in nuclear safety on condition that the safety is ensured technically and mechanically

125I-DPDYN, monoiodo [D-Pro10]- dynorphin (1-11), is an effective and useful tool for the study of kappa opioid receptors

International Nuclear Information System (INIS)

Gairin, J.E.; Jomary, C.; Cros, J.; Meunier, J.C.

1986-01-01

Iodination of the kappa-selective peptide DPDYN, [D-Pro10]-dynorphin (1-11), has been performed. The non radioactive monoiodo derivative of DPDYN retains kappa-selectivity (kappa/mu = 48 and kappa/delta = 140), despite a general but moderate decrease in affinity. Radioiodination of DPDYN leads to the monoiodinated peptide (S.A 700-800 Ci/mmol) which interacts specifically and reversibly with the kappa-sites in guinea-pig cerebellum membranes with high affinity (KD = 0.12-0.18 nM). In guinea-pig brain (mu-delta-kappa) and rabbit cerebellum (kappa much less than mu), 125 I-DPDYN discriminates between kappa- and other (mu, delta) binding sites. We have used this new labelled probe for the direct, precise and rapid (exposure time less than 100 hours) visualization of kappa-sites in guinea-pig and rabbit cerebellar slices using autoradiography

Turkish Scorzonera Species Extracts Attenuate Cytokine Secretion via Inhibition of NF-kappa B Activation, Showing Anti-Inflammatory Effect in Vitro

Czech Academy of Sciences Publication Activity Database

Acikara, O. B.; Hošek, J.; Babula, P.; Cvačka, Josef; Buděšínský, Miloš; Dračínský, Martin; Iscan, G. S.; Kadlecová, D.; Ballová, L.; Šmejkal, K.

2016-01-01

Roč. 21, č. 1 (2016), č. článku 43. ISSN 1420-3049 Institutional support: RVO:61388963 Keywords : anti-inflammatory activity * IL-1 beta * NF-kappa B * Scorzonera * phenolic * TNF-alpha * triterpen Subject RIV: CC - Organic Chemistry Impact factor: 2.861, year: 2016 http://www.mdpi.com/1420-3049/21/1/43/htm

The human factor and organization to support nuclear power plant operators

International Nuclear Information System (INIS)

Naumov, V.I.

1993-01-01

Analysis reveals three basic factors which affect the safety of nuclear power reactors: (1) Internal physical properties of the reactor which provide self protection under breakdown and accident conditions; (2) The reliability of technical systems which provide monitoring, control, accident prevention, heat release, and localization of hazardous products during accidents; (3) Reliability of the reactor control personnel. The last of these factors is usually called the human factor. From published data, this factor makes a large contribution to the downtime and accident statistics at nuclear power plants: from 30 to 80% in various countries. Today the importance of the human factor in operating a nuclear power units is rather well recognized. Current ideas on how to increase the reliability of a human operator are reflected in IAEA recommendations and domestic official documents. The concept of 'a culture of safety' is introduced. Basic types of actions to increase the reliability of personnel who control a nuclear reactor are discussed, including: (1) The qualifying and psychological selection and the training of candidates on the operator's obligations. (2) The automation of routine operations which do not require the operator's intellect. (3) Perfecting the work place, information input to the operator, and the organization of the controls

Bacterial endotoxin enhances colorectal cancer cell adhesion and invasion through TLR-4 and NF-kappaB-dependent activation of the urokinase plasminogen activator system.

LENUS (Irish Health Repository)

Killeen, S D

2009-05-19

Perioperative exposure to lipopolysaccharide (LPS) is associated with accelerated metastatic colorectal tumour growth. LPS directly affects cells through Toll-like receptor 4 (TLR-4) and the transcription factor NF-kappaB. The urokinase plasminogen activator (u-PA) system is intimately implicated in tumour cell extracellular matrix (ECM) interactions fundamental to tumour progression. Thus we sought to determine if LPS directly induces accelerated tumour cell ECM adhesion and invasion through activation of the u-PA system and to elucidate the cellular pathways involved. Human colorectal tumour cell lines were stimulated with LPS. u-PA concentration, u-PA activity, active u-PA, surface urokinase plasminogen activator receptor (u-PAR) and TLR-4 expression were assessed by ELISA, colorimetric assay, western blot analysis and flow cytometry respectively. In vitro tumour cell vitronectin adhesion and ECM invasion were analysed by vitronectin adhesion assay and ECM invasion chambers. u-PA and u-PAR function was inhibited with anti u-PA antibodies or the selective u-PA inhibitors amiloride or WXC-340, TLR-4 by TLR-4-blocking antibodies and NF-kappaB by the selective NF-kappaB inhibitor SN-50. LPS upregulates u-PA and u-PAR in a dose-dependent manner, enhancing in vitro tumour cell vitronectin adhesion and ECM invasion by >40% (P<0.01). These effects were ameliorated by u-PA and u-PAR inhibition. LPS activates NF-kappaB through TLR-4. TLR-4 and NF-kappaB inhibition ameliorated LPS-enhanced u-PA and u-PAR expression, tumour cell vitronectin adhesion and ECM invasion. LPS promotes tumour cell ECM adhesion and invasion through activation of the u-PA system in a TLR-4- and NF-kappaB-dependent manner.

Oligonol Ameliorates CCl4-Induced Liver Injury in Rats via the NF-Kappa B and MAPK Signaling Pathways

Directory of Open Access Journals (Sweden)

Jeonghyeon Bak

2016-01-01

Full Text Available Oxidative stress is thought to be a key risk factor in the development of hepatic diseases. Blocking or retarding the reactions of oxidation and the inflammatory process by antioxidants could be a promising therapeutic intervention for prevention or treatment of liver injuries. Oligonol is a low molecular weight polyphenol containing catechin-type monomers and oligomers derived from lychee fruit. In this study, we investigated the anti-inflammatory effect of oligonol on carbon tetrachloride- (CCl4- induced acute hepatic injury in rats. Oral administration of oligonol (10 or 50 mg/kg reduced CCl4-induced abnormalities in liver histology and serum AST and serum ALT levels. Oligonol treatment attenuated the CCl4-induced production of inflammatory mediators, including TNF-α, IL-1β, cyclooxygenase-2 (COX-2, and inducible nitric oxide synthase (iNOS mRNA levels. Western blot analysis showed that oligonol suppressed proinflammatory nuclear factor-kappa B (NF-κB p65 activation, phosphorylation of extracellular signal-regulated kinase (ERK, c-Jun NH2-terminal kinase (JNK, and p38 mitogen-activated protein kinases (MAPKs as well as Akt. Oligonol exhibited strong antioxidative activity in vitro and in vivo, and hepatoprotective activity against t-butyl hydroperoxide-induced HepG2 cells. Taken together, oligonol showed antioxidative and anti-inflammatory effects in CCl4-intoxicated rats by inhibiting oxidative stress and NF-κB activation via blockade of the activation of upstream kinases including MAPKs and Akt.

Critical human-factors issues in nuclear-power regulation and a recommended comprehensive human-factors long-range plan. Critical discussion of human factors areas of concern

International Nuclear Information System (INIS)

Hopkins, C.O.; Snyder, H.L.; Price, H.E.; Hornick, R.J.; Mackie, R.R.; Smillie, R.J.; Sugarman, R.C.

1982-08-01

This comprehensive long-range human factors plan for nuclear reactor regulation was developed by a Study Group of the Human Factors Society, Inc. This Study Group was selected by the Executive Council of the Society to provide a balanced, experienced human factors perspective to the applications of human factors scientific and engineering knowledge to nuclear power generation. The report is presented in three volumes. Volume 1 contains an Executive Summary of the 18-month effort and its conclusions. Volume 2 summarizes all known nuclear-related human factors activities, evaluates these activities wherever adequate information is available, and describes the recommended long-range (10-year) plan for human factors in regulation. Volume 3 elaborates upon each of the human factors issues and areas of recommended human factors involvement contained in the plan, and discusses the logic that led to the recommendations

Hemistepsin A ameliorates acute inflammation in macrophages via inhibition of nuclear factor-κB and activation of nuclear factor erythroid 2-related factor 2.

Science.gov (United States)

Kim, Jae Kwang; Lee, Ji Eun; Jung, Eun Hye; Jung, Ji Yun; Jung, Dae Hwa; Ku, Sae Kwang; Cho, Il Je; Kim, Sang Chan

2018-01-01

Hemistepsin A (HsA) is a sesquiterpene lactone isolated from Hemistepta lyrata (Bunge) Bunge. We investigated the anti-inflammatory effects of HsA and sought to determine its mechanisms of action in macrophages. HsA pretreatment inhibited nitric oxide production, and reduced the expression of iNOS and COX-2 in Toll-like receptor ligand-stimulated RAW 264.7 cells. Additionally, HsA decreased the secretion of proinflammatory cytokines in lipopolysaccharide (LPS)-stimulated Kupffer cells as well as in RAW 264.7 cells. HsA inhibited phosphorylation of IKKα/β and degradation of IκBα, resulting in decreased nuclear translocation of nuclear factor-κB (NF-κB) and its transcriptional activity. Moreover, HsA phosphorylated nuclear factor erythroid 2-related factor 2 (Nrf2), increased expression levels of antioxidant genes, and attenuated LPS-stimulated H 2 O 2 production. Phosphorylation of p38 and c-Jun N-terminal kinase was required for HsA-mediated Nrf2 phosphorylation. In a D-galactosamine/LPS-induced liver injury model, HsA ameliorated D-galactosamine/LPS-induced hepatocyte degeneration and inflammatory cells infiltration. Moreover, immunohistochemical analyses using nitrotyrosine, 4-hydroxynonenal, and cleaved poly (ADP-ribose) polymerase antibodies revealed that HsA protected the liver from oxidative stress. Furthermore, HsA reduced the numbers of proinflammatory cytokine-positive cells in hepatic tissues. Thus, these results suggest HsA may be a promising natural product to manage inflammation-mediated tissue injuries through inhibition of NF-κB and activation of Nrf2. Copyright © 2017 Elsevier Ltd. All rights reserved.

High constitutive activity of a virus-encoded seven transmembrane receptor in the absence of the conserved DRY motif (Asp-Arg-Tyr) in transmembrane helix 3

DEFF Research Database (Denmark)

Rosenkilde, Mette M; Kledal, Thomas N; Schwartz, Thue W

2005-01-01

-driven transcriptional activity through a pertussis toxin-sensitive manner. Gs and Gq were not activated constitutively as determined by the lack of inositol phosphate turnover and activities of the three transcription factors: cAMP response element-binding protein (CREB), nuclear factor-kappaB, and nuclear factor...

Influenza A virus inhibits type I IFN signaling via NF-kappaB-dependent induction of SOCS-3 expression.

Directory of Open Access Journals (Sweden)

Eva-K Pauli

2008-11-01

Full Text Available The type I interferon (IFN system is a first line of defense against viral infections. Viruses have developed various mechanisms to counteract this response. So far, the interferon antagonistic activity of influenza A viruses was mainly observed on the level of IFNbeta gene induction via action of the viral non-structural protein 1 (NS1. Here we present data indicating that influenza A viruses not only suppress IFNbeta gene induction but also inhibit type I IFN signaling through a mechanism involving induction of the suppressor of cytokine signaling-3 (SOCS-3 protein. Our study was based on the observation that in cells that were infected with influenza A virus and subsequently stimulated with IFNalpha/beta, phosphorylation of the signal transducer and activator of transcription protein 1 (STAT1 was strongly reduced. This impaired STAT1 activation was not due to the action of viral proteins but rather appeared to be induced by accumulation of viral 5' triphosphate RNA in the cell. SOCS proteins are potent endogenous inhibitors of Janus kinase (JAK/STAT signaling. Closer examination revealed that SOCS-3 but not SOCS-1 mRNA levels increase in an RNA- and nuclear factor kappa B (NF-kappaB-dependent but type I IFN-independent manner early in the viral replication cycle. This direct viral induction of SOCS-3 mRNA and protein expression appears to be relevant for suppression of the antiviral response since in SOCS-3 deficient cells a sustained phosphorylation of STAT1 correlated with elevated expression of type I IFN-dependent genes. As a consequence, progeny virus titers were reduced in SOCS-3 deficient cells or in cells were SOCS-3 expression was knocked-down by siRNA. These data provide the first evidence that influenza A viruses suppress type I IFN signaling on the level of JAK/STAT activation. The inhibitory effect is at least in part due to the induction of SOCS-3 gene expression, which results in an impaired antiviral response.

Caseinomacropeptide self-association is dependent on whether the peptide is free or restricted in kappa-casein

DEFF Research Database (Denmark)

Mikkelsen, T.L.; Frokiaer, H.; Topp, C.

2005-01-01

There is a general agreement that the experimentally determined molecular weight (MW) of caseinomacropeptide (CMP) is greater than the theoretical MW. Some studies suggest that this is due to a pH-dependent aggregation of monomeric CMP. How this aggregation is influenced by pH is not understood. ...... are irreversibly associated, CMP in kappa-CN may associate reversibly in a pH-dependent manner. We suggest that interactions between para-kappa-CN parts of the kappa-CN molecules may be a requisite for the pH-dependent dissociation/association....

Imaging analysis of nuclear antiviral factors through direct detection of incoming adenovirus genome complexes

Energy Technology Data Exchange (ETDEWEB)

Komatsu, Tetsuro [Microbiologie Fondamentale et Pathogénicité, MFP CNRS UMR 5234, Université de Bordeaux, Bordeaux 33076 (France); Department of Infection Biology, Faculty of Medicine, University of Tsukuba, Tsukuba 305-8575 (Japan); Will, Hans [Department of Tumor Biology, University Hospital Hamburg-Eppendorf, 20246 Hamburg (Germany); Nagata, Kyosuke [Department of Infection Biology, Faculty of Medicine, University of Tsukuba, Tsukuba 305-8575 (Japan); Wodrich, Harald, E-mail: harald.wodrich@u-bordeaux.fr [Microbiologie Fondamentale et Pathogénicité, MFP CNRS UMR 5234, Université de Bordeaux, Bordeaux 33076 (France)

2016-04-22

Recent studies involving several viral systems have highlighted the importance of cellular intrinsic defense mechanisms through nuclear antiviral proteins that restrict viral propagation. These factors include among others components of PML nuclear bodies, the nuclear DNA sensor IFI16, and a potential restriction factor PHF13/SPOC1. For several nuclear replicating DNA viruses, it was shown that these factors sense and target viral genomes immediately upon nuclear import. In contrast to the anticipated view, we recently found that incoming adenoviral genomes are not targeted by PML nuclear bodies. Here we further explored cellular responses against adenoviral infection by focusing on specific conditions as well as additional nuclear antiviral factors. In line with our previous findings, we show that neither interferon treatment nor the use of specific isoforms of PML nuclear body components results in co-localization between incoming adenoviral genomes and the subnuclear domains. Furthermore, our imaging analyses indicated that neither IFI16 nor PHF13/SPOC1 are likely to target incoming adenoviral genomes. Thus our findings suggest that incoming adenoviral genomes may be able to escape from a large repertoire of nuclear antiviral mechanisms, providing a rationale for the efficient initiation of lytic replication cycle. - Highlights: • Host nuclear antiviral factors were analyzed upon adenovirus genome delivery. • Interferon treatments fail to permit PML nuclear bodies to target adenoviral genomes. • Neither Sp100A nor B targets adenoviral genomes despite potentially opposite roles. • The nuclear DNA sensor IFI16 does not target incoming adenoviral genomes. • PHF13/SPOC1 targets neither incoming adenoviral genomes nor genome-bound protein VII.

Imaging analysis of nuclear antiviral factors through direct detection of incoming adenovirus genome complexes

International Nuclear Information System (INIS)

Komatsu, Tetsuro; Will, Hans; Nagata, Kyosuke; Wodrich, Harald

2016-01-01

Recent studies involving several viral systems have highlighted the importance of cellular intrinsic defense mechanisms through nuclear antiviral proteins that restrict viral propagation. These factors include among others components of PML nuclear bodies, the nuclear DNA sensor IFI16, and a potential restriction factor PHF13/SPOC1. For several nuclear replicating DNA viruses, it was shown that these factors sense and target viral genomes immediately upon nuclear import. In contrast to the anticipated view, we recently found that incoming adenoviral genomes are not targeted by PML nuclear bodies. Here we further explored cellular responses against adenoviral infection by focusing on specific conditions as well as additional nuclear antiviral factors. In line with our previous findings, we show that neither interferon treatment nor the use of specific isoforms of PML nuclear body components results in co-localization between incoming adenoviral genomes and the subnuclear domains. Furthermore, our imaging analyses indicated that neither IFI16 nor PHF13/SPOC1 are likely to target incoming adenoviral genomes. Thus our findings suggest that incoming adenoviral genomes may be able to escape from a large repertoire of nuclear antiviral mechanisms, providing a rationale for the efficient initiation of lytic replication cycle. - Highlights: • Host nuclear antiviral factors were analyzed upon adenovirus genome delivery. • Interferon treatments fail to permit PML nuclear bodies to target adenoviral genomes. • Neither Sp100A nor B targets adenoviral genomes despite potentially opposite roles. • The nuclear DNA sensor IFI16 does not target incoming adenoviral genomes. • PHF13/SPOC1 targets neither incoming adenoviral genomes nor genome-bound protein VII.

Availability improvement factors at Taipower's nuclear power plant system

International Nuclear Information System (INIS)

Chen, J.H.

1985-01-01

Sufficient electricity to meet the needs of a growing industrial economy, is one of the most important factors in the total economic development of a nation. Currently, nuclear power is considered one of the most economical and available sources of energy. To keep pace with Taiwan's rapid economic development, while also observing our government's policy of diversifying the requirements for imported forms of energy, Taiwan Power Company has embarked upon an ambitious of nuclear power plant construction. This paper discusses the improvement of Taiwan's nuclear power plants. At the present time, Taipower has completed three nuclear power plants. Two of these are located in northern Taiwan, along the East China Sea, while the third is on the southern tip of Taiwan, bordering the South China Sea. These three plants, each with two nuclear generating units, comprise a total nuclear generating capacity of 5144 MWe

Capacity factor of nuclear power stations in Japan in fiscal year 1984

International Nuclear Information System (INIS)

Agawa, Takashi

1985-01-01

In Japan presently a total of 28 nuclear power plants are in operation with aggregate capacity 20,561 MW, 22 % of the total power generation. Around 1975 there occurred such as stress corrosion cracking and to repair them much time was consumed, leading to the low capacity factor. With such troubles removed, in fiscal 1984, the capacity factor on average of the nuclear power stations is 73.9 %, the highest so far. Contributing to this are long period of the continuous operation, short period of the periodical inspection and increase in the in-operation capacity factor. Contents are the following : construction state of nuclear power stations, operation state in fiscal 1984, causes leading to the high capacity factor, future directions. (Mori, K.)

Nuclear safety and human factors: the French factory of expertise

International Nuclear Information System (INIS)

Rolina, G.

2009-01-01

The French regulation of the nuclear safety is based on the maintaining of a deep technical dialogue between the nuclear safety authority, the I.R.S.N. (Institute of radiation protection and nuclear safety) and the nuclear operators. This type of risk management is called 'french coking' by the Anglo-Saxons, followers of stricter regulatory approach, more readable by the civil society. This technical dialogue is not without quality, especially in the field of human and organizational factors where it allows to improve the know how situation that stays incomplete. (N.C.)

Human factor in the process of nuclear power development

International Nuclear Information System (INIS)

Enenkl, V.

The building up of nuclear power requires the training not only of personnel but of the whole population as well. Professional workers in nuclear power facilities production and personnel operating the equipment of nuclear power plants must be on a high technical and managerial level. The important quality of such personnel is their reliability and responsibility. The human factor influences the level, quality and thereby also the service-life of the machines and equipment and their operation. The improvement of the quality of work in nuclear power production depends on upgrading the scientific and technical level of workers and personnel, their training, in-service education and the raising of the social standing. (B.H.)

Correction factors for photon spectrometry in nuclear parameters study

International Nuclear Information System (INIS)

Patrao, Karla Cristina de Souza

2004-10-01

The goal of this work was the determination, using metrologic severity, the factors of correction for coincidences XX, Xγ and γγ and the factors of transference of efficiency for use in gamma spectrometry. On this way, it was carried through by determination of nuclear parameters of a nuclide used in medicine diagnostic ( 201 Tl) and the standardization of two environmental samples, of regular and irregular geometry, proceeding from the residual (ashes and slag) from the nuclear industry. The results shows that this adopted methodology is valid, and it allows its application for many different nuclides, including complex decay schema nuclides, using only photons spectrometry techniques on semiconductor detectors. (author)

Macrophage-secreted factors induce adipocyte inflammation and insulin resistance

International Nuclear Information System (INIS)

Permana, Paska A.; Menge, Christopher; Reaven, Peter D.

2006-01-01

Macrophage infiltration into adipose tissue increases with obesity, a condition associated with low-grade inflammation and insulin resistance. We investigated the direct effects of macrophage-secreted factors on adipocyte inflammation and insulin resistance. 3T3-L1 adipocytes incubated with media conditioned by RAW264.7 macrophages (RAW-CM) showed dramatically increased transcription of several inflammation-related genes, greater nuclear factor kappa B (NF-κB) activity, and enhanced binding of U937 monocytes. All of these effects were prevented by co-incubation with pyrrolidinedithiocarbamate, an NF-κB inhibitor. Adipocytes incubated with RAW-CM also released more non-esterified fatty acids and this increased lipolysis was not suppressed by insulin. In addition, RAW-CM treatment decreased insulin-stimulated glucose uptake in adipocytes. Taken together, these results indicate that macrophage-secreted factors induce inflammatory responses and reduce insulin responsiveness in adipocytes. These effects of macrophage-secreted factors on adipocytes may contribute significantly to the systemic inflammation and insulin resistance associated with obesity

Inactivation of nuclear factor κB by MIP-based drug combinations augments cell death of breast cancer cells

Directory of Open Access Journals (Sweden)

Subramaniam M

2018-05-01

Full Text Available Menaga Subramaniam,1 Su Ki Liew,1 Lionel LA In,2 Khalijah Awang,3,4 Niyaz Ahmed,5 Noor Hasima Nagoor1,6 1Institute of Biological Science (Genetics & Molecular Biology, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia; 2Department of Biotechnology, Faculty of Applied Sciences, UCSI University, Kuala Lumpur, Malaysia; 3Centre for Natural Product Research and Drug Discovery (CENAR, University of Malaya, Kuala Lumpur, Malaysia; 4Department of Chemistry, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia; 5Pathogen Biology Laboratory, Department of Biotechnology and Bioinformatics, University of Hyderabad, Hyderabad, India; 6Centre for Research in Biotechnology for Agriculture (CEBAR, University of Malaya, Kuala Lumpur, Malaysia Background: Drug combination therapy to treat cancer is a strategic approach to increase successful treatment rate. Optimizing combination regimens is vital to increase therapeutic efficacy with minimal side effects. Materials and methods: In the present study, we evaluated the in vitro cytotoxicity of double and triple combinations consisting of 1'S-1'-acetoxychavicol acetate (ACA, Mycobacterium indicus pranii (MIP and cisplatin (CDDP against 14 various human cancer cell lines to address the need for more effective therapy. Our data show synergistic effects in MCF-7 cells treated with MIP:ACA, MIP:CDDP and MIP:ACA:CDDP combinations. The type of interaction between MIP, ACA and CDDP was evaluated based on combination index being <0.8 for synergistic effect. Identifying the mechanism of cell death based on previous studies involved intrinsic apoptosis and nuclear factor kappa B (NF-κB and tested in Western blot analysis. Inactivation of NF-κB was confirmed by p65 and IκBα, while intrinsic apoptosis pathway activation was confirmed by caspase-9 and Apaf-1 expression Results: All combinations confirmed intrinsic apoptosis activation and NF-κB inactivation. Conclusion: Double and triple

Phenotyping polyclonal kappa and lambda light chain molecular mass distributions in patient serum using mass spectrometry.

Science.gov (United States)

Barnidge, David R; Dasari, Surendra; Ramirez-Alvarado, Marina; Fontan, Adrian; Willrich, Maria A V; Tschumper, Renee C; Jelinek, Diane F; Snyder, Melissa R; Dispenzieri, Angela; Katzmann, Jerry A; Murray, David L

2014-11-07

We previously described a microLC-ESI-Q-TOF MS method for identifying monoclonal immunoglobulins in serum and then tracking them over time using their accurate molecular mass. Here we demonstrate how the same methodology can be used to identify and characterize polyclonal immunoglobulins in serum. We establish that two molecular mass distributions observed by microLC-ESI-Q-TOF MS are from polyclonal kappa and lambda light chains using a combination of theoretical molecular masses from gene sequence data and the analysis of commercially available purified polyclonal IgG kappa and IgG lambda from normal human serum. A linear regression comparison of kappa/lambda ratios for 74 serum samples (25 hypergammaglobulinemia, 24 hypogammaglobulinemia, 25 normal) determined by microflowLC-ESI-Q-TOF MS and immunonephelometry had a slope of 1.37 and a correlation coefficient of 0.639. In addition to providing kappa/lambda ratios, the same microLC-ESI-Q-TOF MS analysis can determine the molecular mass for oligoclonal light chains observed above the polyclonal background in patient samples. In 2 patients with immune disorders and hypergammaglobulinemia, we observed a skewed polyclonal molecular mass distribution which translated into biased kappa/lambda ratios. Mass spectrometry provides a rapid and simple way to combine the polyclonal kappa/lambda light chain abundance ratios with the identification of dominant monoclonal as well as oligoclonal light chain immunoglobulins. We anticipate that this approach to evaluating immunoglobulin light chains will lead to improved understanding of immune deficiencies, autoimmune diseases, and antibody responses.

Rottlerin inhibits the nuclear factor kappaB/cyclin-D1 cascade in MCF-7 breast cancer cells

Czech Academy of Sciences Publication Activity Database

Torricelli, C.; Fortino, V.; Capurro, E.; Valacchi, G.; Pacini, A.; Muscettola, M.; Souček, Karel; Maioli, E.

2008-01-01

Roč. 82, 11-12 (2008), s. 638-643 ISSN 0024-3205 R&D Projects: GA ČR(CZ) GA310/07/0961; GA AV ČR(CZ) 1QS500040507 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : Rottlerin * MCF-7 cells * cyclin-D1 Subject RIV: BO - Biophysics Impact factor: 2.583, year: 2008

Statistical factors affecting the success of nuclear operations

International Nuclear Information System (INIS)

Sunder, S.; Stephenson, J.R.; Hochman, D.

1999-01-01

In this article, the authors present a statistical analysis to determine the operational, financial, technical, and managerial factors that most significantly affect the success of nuclear operations. The study analyzes data for over 70 nuclear plants and 40 operating companies over a period of five years in order to draw conclusions that they hope will be of interest to utility companies and public utility commissions as they seek ways to improve rates of success in nuclear operations. Some of these conclusions will not be surprising--for example, that older plants have heavier maintenance requirements--but others are less intuitive. For instance, the observation that operators of fewer plants have lower costs suggests that any experience curve benefits associated with managing multiple nuclear facilities is overshadowed by the logistic problems of multiple facilities. After presenting a brief history of nuclear power in America, the authors outline the motivations of the study and the methodology of their analysis. They end the article with the results of the study and discuss some of the managerial implications of these findings

A report on human factors in nuclear safety

International Nuclear Information System (INIS)

1983-03-01

Following the Three Mile Island incident of 1979, studies were undertaken by the Atomic Energy Control Board (AECB), in-house and through outside consultants, to address the role of human factors in the regulatory process. This report by the Advisory Committee on Nuclear Safety (ACNS) comments briefly on these studies and offers suggestions which would promote a more formal treatment of human factors by the AECB

Human factors engineering applied to Control Centre Design of a research nuclear reactor

Energy Technology Data Exchange (ETDEWEB)

Farias, Larissa P. de; Santos, Isaac J.A. Luquetti dos; Carvalho, Paulo V.R., E-mail: larissapfarias@ymail.com [Instituto de Engenharia Nuclear (DENN/SEESC/IEN/CNEN-RJ), Rio de Janeiro, RJ (Brazil). Lab, de Usabilidade e Confiabilidade Humana; Monteiro, Beany G. [Universidade Federal do Rio Janeiro (UFRJ), Rio Janeiro, RJ (Brazil). Departamento de Desenho Industrial

2017-07-01

The Human Factors Engineering (HFE) program is an essential aspect for the design of nuclear installations. The overall aim of the HFE program is the improvement of the operational reliability and safety of plant operation. The HFE program main purpose is to ensure that human factor practices are incorporated into the plant design, emphasizing man-machine interface issues and design improvement of the nuclear reactor Control Centre. The Control Centre of nuclear reactor is a combination of control rooms, control suites and local control stations, which are functionally connected and located on the reactor site. The objective of this paper is to present a design approach for the Control Centre of a nuclear reactor used to produce radioisotopes and for nuclear research, including human factor issues. The design approach is based on participatory design principles, using human factor standards, ergonomic guidelines, and the participation of a multidisciplinary team during all design phases. Using the information gathered, an initial sketch 3D of the Control Centre was developed. (author)

Human factors engineering applied to Control Centre Design of a research nuclear reactor

International Nuclear Information System (INIS)

Farias, Larissa P. de; Santos, Isaac J.A. Luquetti dos; Carvalho, Paulo V.R.; Monteiro, Beany G.

2017-01-01

The Human Factors Engineering (HFE) program is an essential aspect for the design of nuclear installations. The overall aim of the HFE program is the improvement of the operational reliability and safety of plant operation. The HFE program main purpose is to ensure that human factor practices are incorporated into the plant design, emphasizing man-machine interface issues and design improvement of the nuclear reactor Control Centre. The Control Centre of nuclear reactor is a combination of control rooms, control suites and local control stations, which are functionally connected and located on the reactor site. The objective of this paper is to present a design approach for the Control Centre of a nuclear reactor used to produce radioisotopes and for nuclear research, including human factor issues. The design approach is based on participatory design principles, using human factor standards, ergonomic guidelines, and the participation of a multidisciplinary team during all design phases. Using the information gathered, an initial sketch 3D of the Control Centre was developed. (author)

Human factors engineering plan for reviewing nuclear plant modernization programs

International Nuclear Information System (INIS)

O'Hara, John; Higgins, James

2004-12-01

The Swedish Nuclear Power Inspectorate reviews the human factors engineering (HFE) aspects of nuclear power plants (NPPs) involved in the modernization of the plant systems and control rooms. The purpose of a HFE review is to help ensure personnel and public safety by verifying that accepted HFE practices and guidelines are incorporated into the program and nuclear power plant design. Such a review helps to ensure the HFE aspects of an NPP are developed, designed, and evaluated on the basis of a structured top-down system analysis using accepted HFE principles. The review addresses eleven HFE elements: HFE Program Management, Operating Experience Review, Functional Requirements Analysis and Allocation, Task Analysis, Staffing, Human Reliability Analysis, Human-System Interface Design, Procedure Development, Training Program Development, Human Factors Verification and Validation, and Design Implementation

Human factors engineering plan for reviewing nuclear plant modernization programs

Energy Technology Data Exchange (ETDEWEB)

O' Hara, John; Higgins, James [Brookhaven National Laboratory, Upton, NY (United States)

2004-12-01

The Swedish Nuclear Power Inspectorate reviews the human factors engineering (HFE) aspects of nuclear power plants (NPPs) involved in the modernization of the plant systems and control rooms. The purpose of a HFE review is to help ensure personnel and public safety by verifying that accepted HFE practices and guidelines are incorporated into the program and nuclear power plant design. Such a review helps to ensure the HFE aspects of an NPP are developed, designed, and evaluated on the basis of a structured top-down system analysis using accepted HFE principles. The review addresses eleven HFE elements: HFE Program Management, Operating Experience Review, Functional Requirements Analysis and Allocation, Task Analysis, Staffing, Human Reliability Analysis, Human-System Interface Design, Procedure Development, Training Program Development, Human Factors Verification and Validation, and Design Implementation.

Novel selective kappa-opioid ligands.

Science.gov (United States)

Peeters, O M; Jamroz, D; Blaton, N M; De Ranter, C J

1999-03-15

The single-crystal X-ray structures of (-)-dimethyl[(2S)-1-(5,6,7,8- tetrahydro-5-oxonaphthalene-2-acetyl)piperidin-2-ylmethyl ]ammonium chloride, C20H29N2O2+.Cl-(BRL-53001A), and (-)-ethylmethyl[(2S)-1-(5,6,7,8-tetrahydro-5-oxonaphthalene- 2- acetyl)piperidin-2-ylmethyl]-ammonium chloride dihydrate, C21H31N2O2+.Cl-.2H2O (BRL-53188A), have been determined. The two molecules have different conformations in the 1-tetralon-6-ylacetyl residue but the same conformation in the 1-acetyl-2-(dialkylaminomethyl)piperidine moiety. The conformations found are in agreement with the required chemical features for kappa affinity and antinociceptive potency.

Targeting Nuclear Factor kappa B for the Treatment of Prostate Cancer

National Research Council Canada - National Science Library

Sweeney, Christopher

2004-01-01

.... With the use of cDNA array technology, we have shown that multiple genes associated with the hallmarks of cancer and that are under NFkB control are decreased when cancer and endothelial cells...

Prothymosin α overexpression contributes to the development of pulmonary emphysema

Science.gov (United States)

Su, Bing-Hua; Tseng, Yau-Lin; Shieh, Gia-Shing; Chen, Yi-Cheng; Shiang, Ya-Chieh; Wu, Pensee; Li, Kuo-Jung; Yen, Te-Hsin; Shiau, Ai-Li; Wu, Chao-Liang

2013-01-01

Emphysema is one of the disease conditions that comprise chronic obstructive pulmonary disease. Prothymosin α transgenic mice exhibit an emphysema phenotype, but the pathophysiological role of prothymosin α in emphysema remains unclear. Here we show that prothymosin α contributes to the pathogenesis of emphysema by increasing acetylation of histones and nuclear factor-kappaB, particularly upon cigarette smoke exposure. We find a positive correlation between prothymosin α levels and the severity of emphysema in prothymosin α transgenic mice and emphysema patients. Prothymosin α overexpression increases susceptibility to cigarette smoke-induced emphysema, and cigarette smoke exposure further enhances prothymosin α expression. We show that prothymosin α inhibits the association of histone deacetylases with histones and nuclear factor-kappaB, and that prothymosin α overexpression increases expression of nuclear factor-kappaB-dependent matrix metalloproteinase 2 and matrix metalloproteinase 9, which are found in the lungs of patients with chronic obstructive pulmonary disease. These results demonstrate the clinical relevance of prothymosin α in regulating acetylation events during the pathogenesis of emphysema. PMID:23695700

Low-Dose Radiation Promotes Dendritic Cell Migration and IL-12 Production via the ATM/NF-KappaB Pathway.

Science.gov (United States)

Yu, Nan; Wang, Sinian; Song, Xiujun; Gao, Ling; Li, Wei; Yu, Huijie; Zhou, Chuanchuan; Wang, Zhenxia; Li, Fengsheng; Jiang, Qisheng

2018-04-01

For dendritic cells (DCs) to initiate an immune response, their ability to migrate and to produce interleukin-12 (IL-12) is crucial. It has been previously shown that low-dose radiation (LDR) promoted IL-12 production by DCs, resulting in increased DC activity that contributed to LDR hormesis in the immune system. However, the molecular mechanism of LDR-induced IL-12 production, as well as the effect of LDR on DC migration capacity require further elucidation. Using the JAWSII immortalized mouse dendritic cell line, we showed that in vitro X-ray irradiation (0.2 Gy) of DCs significantly increased DC migration and IL-12 production, and upregulated CCR7. The neutralizing antibody against CCR7 has been shown to abolish LDR-enhanced DC migration, demonstrating that CCR7 mediates LDR-promoting DC migration. We identified nuclear factor kappaB (NF-κB) as the central signaling pathway that mediated LDR-enhanced expression of IL-12 and CCR7 based on findings that 0.2 Gy X-ray irradiation activated NF-κB, showing increased nuclear p65 translocation and NF-κB DNA-binding activity, while an NF-κB inhibitor blocked LDR-enhanced expression of IL-12 and CCR7, as well as DC migration. Finally, we demonstrated that 0.2 Gy X-ray irradiation promoted ATM phosphorylation and reactive oxygen species generation; however, only the ATM inhibitor abolished the LDR-induced NF-κB-mediated expression of IL-12 and CCR7. Altogether, our data show that exposure to LDR resulted in a hormetic effect on DCs regarding CCR7-mediated migration and IL-12 production by activating the ATM/NF-κB pathway.

Gauge invariance and the {kappa}-g{sub l} relation

Energy Technology Data Exchange (ETDEWEB)

Arima, A [Japan Science Foundation, 2-1 Kitanomaru Koen, Chiyoda-ku, Tokyo 102-0091 (Japan); Bentz, W [Department of Physics, School of Science, Tokai University, 1117 Kita-Kaname, Hiratsuka-shi 259-1207 (Japan); Enders, J [Institut fuer Kernphysik, Technische Universitaet Darmstadt, Schlossgartenstr. 9, D-64289 Darmstadt (Germany); Richter, A [Institut fuer Kernphysik, Technische Universitaet Darmstadt, Schlossgartenstr. 9, D-64289 Darmstadt (Germany)

2005-01-01

The connection between the enhancement factor of the photonuclear E1 sum rule and the orbital angular momentum g-factor of a bound nucleon is discussed in the framework of the Landau-Migdal theory for isospin asymmetric nuclear matter, and compared to empirical informations.

High glucose induces inflammatory cytokine through protein kinase C-induced toll-like receptor 2 pathway in gingival fibroblasts

Energy Technology Data Exchange (ETDEWEB)

Jiang, Shao-Yun, E-mail: jiangshaoyun@yahoo.com [School of Dentistry, Tianjin Medical University, 12 Qi Xiang Tai Street, Heping District, Tianjin 300070 (China); Wei, Cong-Cong; Shang, Ting-Ting; Lian, Qi; Wu, Chen-Xuan [School of Dentistry, Tianjin Medical University, 12 Qi Xiang Tai Street, Heping District, Tianjin 300070 (China); Deng, Jia-Yin, E-mail: yazhou2991@126.com [School of Dentistry, Tianjin Medical University, 12 Qi Xiang Tai Street, Heping District, Tianjin 300070 (China)

2012-10-26

Highlights: Black-Right-Pointing-Pointer High glucose significantly induced TLR2 expression in gingival fibroblasts. Black-Right-Pointing-Pointer High glucose increased NF-{kappa}B p65 nuclear activity, IL-1{beta} and TNF-{alpha} levels. Black-Right-Pointing-Pointer PKC-{alpha}/{delta}-TLR2 pathway is involved in periodontal inflammation under high glucose. -- Abstract: Toll-like receptors (TLRs) play a key role in innate immune response and inflammation, especially in periodontitis. Meanwhile, hyperglycemia can induce inflammation in diabetes complications. However, the activity of TLRs in periodontitis complicated with hyperglycemia is still unclear. In the present study, high glucose (25 mmol/l) significantly induced TLR2 expression in gingival fibroblasts (p < 0.05). Also, high glucose increased nuclear factor kappa B (NF-{kappa}B) p65 nuclear activity, tumor necrosis factor-{alpha} (TNF-{alpha}) and interleukin-l{beta} (IL-1{beta}) levels. Protein kinase C (PKC)-{alpha} and {delta} knockdown with siRNA significantly decreased TLR2 and NF-{kappa}B p65 expression (p < 0.05), whereas inhibition of PKC-{beta} had no effect on TLR2 and NF-{kappa}B p65 under high glucose (p < 0.05). Additional studies revealed that TLR2 knockdown significantly abrogated high-glucose-induced NF-{kappa}B expression and inflammatory cytokine secretion. Collectively, these data suggest that high glucose stimulates TNF-{alpha} and IL-1{beta} secretion via inducing TLR2 through PKC-{alpha} and PKC-{delta} in human gingival fibroblasts.

Application of iota and kappa carrageenans to traditional several food using modified cassava flour

Science.gov (United States)

Al-Baarri, A. N.; Legowo, A. M.; Rizqiati, H.; Widayat; Septianingrum, A.; Sabrina, H. N.; Arganis, L. M.; Saraswati, R. O.; Mochtar, Rr C. P. R.

2018-01-01

Carrageenan has been known well as hydrocolloids that forming viscous dispersions and gels when dispersed in water. The carrageenan has not been widely applied to traditional foods. Therefore, the aim of this research was to determine the effect of kappa and iota carrageenans in traditional food models using modified cassava flour, sugar, and coconut milk. The textural properties, i.e. hardness, cohesiveness, springiness and adhesiveness have been measured using texture analyzer. The study indicated that traditional food models added kappa carrageenan at 2% generated remarkably higher in the hardness, cohesiveness, and springiness than those added iota carrageenan. On the other hand, the reserve result were found in the adhesiveness parameter. As conclusion, kappa carrageenan scan be potentially used for producing traditional foods based on the hard-texture-oriented foods whereas iota carrageenan can be used for the traditional foods with better adhesiveness.

Relationship between organizational factors, safety culture and PSA in nuclear power plant operations

International Nuclear Information System (INIS)

Joksimovich, V.; Orvis, D.D.

1997-01-01

There are four nuclear safety imperatives or ''4Ms'': machine (hardware, design, QA/QC), milieux (operating conditions, environment, natural phenomena), man (human reliability) and management (organizational and management influences). Nuclear safety evaluations as well as evolution of its most powerful tool, Probabilistic Safety Assessment (PSA), followed chronologically the 4M constituents. The nuclear industry worldwide, and the nuclear safety regulators in particular, have been preoccupied with the first M almost to the point of obsession with belated and only intuitive interest in the third and fourth M (human dimension). Human factors or economics in the nuclear industry was an afterthought. Human reliability was essentially born in the aftermath of the Three Mile Island (TMI) accident. Impact of organizational factors on nuclear safety is only in the early stages of R and D. This paper describes some of the concepts being pursued by APG to link organizational factors and safety culture to Human Reliability Analysis (HRA) and to integrate such into probabilistic safety assessment (PSA), e.g. [APG, 1993]. (author). 11 refs, 4 figs, 1 tab

Resveratrol enhances ultraviolet B-induced cell death through nuclear factor-κB pathway in human epidermoid carcinoma A431 cells

International Nuclear Information System (INIS)

Roy, Preeti; Kalra, Neetu; Nigam, Nidhi; George, Jasmine; Ray, Ratan Singh; Hans, Rajendra K.; Prasad, Sahdeo; Shukla, Yogeshwer

2009-01-01

Resveratrol has been reported to suppress cancer progression in several in vivo and in vitro models, whereas ultraviolet B (UVB), a major risk for skin cancer, is known to induce cell death in cancerous cells. Here, we investigated whether resveratrol can sensitize A431 human epidermoid carcinoma cells to UVB-induced cell death. We examined the combined effect of UVB (30 mJ/cm 2 ) and resveratrol (60 μM) on A431 cells. Exposure of A431 carcinoma cells to UVB radiation or resveratrol can inhibit cell proliferation and induce apoptosis. However, the combination of resveratrol and UVB exposure was associated with increased proliferation inhibition of A431 cells compared with either agent alone. Furthermore, results showed that resveratrol and UVB treatment of A431 cells disrupted the nuclear factor-kappaB (NF-κB) pathway by blocking phosphorylation of serine 536 and inactivating NF-κB and subsequent degradation of IκBα, which regulates the expression of survivin. Resveratrol and UVB treatment also decreased the phosphorylation of tyrosine 701 of the important transcription factor signal transducer activator of transcription (STAT1), which in turn inhibited translocation of phospho-STAT1 to the nucleus. Moreover, resveratrol/UVB also inhibited the metastatic protein LIMK1, which reduced the motility of A431 cells. In conclusion, our study demonstrates that the combination of resveratrol and UVB act synergistically against skin cancer cells. Thus, resveratrol is a potential chemotherapeutic agent against skin carcinogenesis.

A regulatory perspective on human factors in nuclear power

International Nuclear Information System (INIS)

Whitfield, D.

1987-01-01

This paper sets out the approaches being taken by the United Kingdom Nuclear Installations Inspectorate (NII) to monitoring the application of human factors principles and practice in the UK industry. The role of NII is outlined, the development of human factors concerns is reviewed, the assessment of the Sizewell 'B' safety case is presented as a particular example, and pertinent future developments in the human factors discipline are proposed. (author)

Factors which could limit the nuclear fuel cycle development

International Nuclear Information System (INIS)

Pecqueur, M.; Barre, B.

1977-01-01

The nuclear fuel cycle is a most important industry for the energy future of the world. It has also a leading part as regards the physical continuity of energy supply of the countries engaged in the nuclear field. The development of this industry is subject to the economic or political constraints involved by the availability of raw materials, technologies or production means. The various limiting factors which could affect the different stages of the fuel cycle are linked with the technical, economic and financial aspects, with the impact on the environment, nuclear safety, risks of non-pacific uses and proliferation of arms. Interesting to note is also the correlation between the fuel cycle development and the problems of energy independence and security of nuclear programs. As a conclusion, the nuclear fuel cycle industry is confronted to difficulties due to its extremely rapid growth (doubling time 5 years) which only few heavy industries have encountered for long periods. It is more over submitted to the political and safety constraints always linked with nuclear matters. The task is therefore a difficult one. But the objective is worth-while since it is a condition to the development of nuclear industry [fr

Homophilic interactions mediated by receptor tyrosine phosphatases mu and kappa. A critical role for the novel extracellular MAM domain

DEFF Research Database (Denmark)

Zondag, G C; Koningstein, G M; Jiang, Y P

1995-01-01

and is found in diverse transmembrane proteins, is not known. We previously reported that both RPTP mu and RPTP kappa can mediate homophilic cell interactions when expressed in insect cells. Here we show that despite their striking structural similarity, RPTP mu and RPTP kappa fail to interact...... in a heterophilic manner. To examine the role of the MAM domain in homophilic binding, we expressed a mutant RPTP mu lacking the MAM domain in insect Sf9 cells. Truncated RPTP mu is properly expressed at the cell surface but fails to promote cell-cell adhesion. Homophilic cell adhesion is fully restored...... in a chimeric RPTP mu molecule containing the MAM domain of RPTP kappa. However, this chimeric RPTP mu does not interact with either RPTP mu or RPTP kappa. These results indicate that the MAM domain of RPTP mu and RPTP kappa is essential for homophilic cell-cell interaction and helps determine the specificity...

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

Directory of Open Access Journals (Sweden)

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.

Enhanced seizures and hippocampal neurodegeneration following kainic acid-induced seizures in metallothionein-I + II-deficient mice

DEFF Research Database (Denmark)

Carrasco, J; Penkowa, M; Hadberg, H

2000-01-01

(NITT) levels and by the expression of MT-I + II, nuclear factor-kappaB (NF-kappaB), and Cu/Zn-superoxide dismutase (Cu/Zn-SOD). MT-I + II deficiency potentiated the oxidative stress caused by KA. Both KA and MT-I + II deficiency significantly affected the expression of MT-III, granulocyte...

The impact of kappa number composition on eucalyptus kraft pulp bleachability

Directory of Open Access Journals (Sweden)

M. M. Costa

2007-03-01

Full Text Available Consumption of chemicals during ECF bleaching of kraft pulp correlates reasonably well with kappa number, which measures with KMnO4 the total amount of oxidizable material in the pulp. However, the method does not distinguish between the oxidizable material in residual lignin and other structures susceptible to oxidation, such as hexenuronic acids (HexAs, extractives and carbonyl groups in the pulp. In this study an attempt is made to separate the main contributors to the kappa number in oxygen - delignified eucalyptus Kraft pulps and evaluate how these fractions behave during ECF bleaching using chlorine dioxide as the sole oxidant (DEDD sequence. Residual lignin and HexAs proved to be the main fractions contributing to the kappa number and chlorine dioxide consumption in ECF bleaching. Pulp bleachability with chlorine dioxide increases with increasing HexAs content of the pulp but chlorine dioxide per se does not react with HexAs. Reduction of pulp with sodium borohydride under conditions for removing carbonyl groups has no impact on bleachability. No correlation was found between the pulp of the extractive content and pulp bleachability. The removal of HexAs prior to ECF bleaching significantly decreases the formation of chlorinated organics in the pulp (OX and filtrates (AOX as well as of oxalic acids in the filtrates.

Delphinidin, a specific inhibitor of histone acetyltransferase, suppresses inflammatory signaling via prevention of NF-{kappa}B acetylation in fibroblast-like synoviocyte MH7A cells

Energy Technology Data Exchange (ETDEWEB)

Seong, Ah-Reum; Yoo, Jung-Yoon; Choi, KyungChul [Department of Biochemistry and Molecular Biology, Center for Chronic Metabolic Disease Research, College of Medicine, Yonsei University, Seoul (Korea, Republic of); Lee, Mee-Hee [Department of Biochemistry and Molecular Biology, Center for Chronic Metabolic Disease Research, College of Medicine, Yonsei University, Seoul (Korea, Republic of); Brain Korea 21 Project for Medical Sciences, Yonsei University, College of Medicine, Seoul (Korea, Republic of); Lee, Yoo-Hyun [Department of Food Science and Nutrition, The University of Suwon, Kyunggi-do (Korea, Republic of); Lee, Jeongmin [Department of Medical Nutrition, Kyung Hee University, Kyunggi-do (Korea, Republic of); Jun, Woojin [Department of Food and Nutrition, Chonnam National University, Gwangju (Korea, Republic of); Kim, Sunoh, E-mail: sunoh@korea.ac.kr [Jeollanamdo Institute of Natural Resources Research, Jeonnam (Korea, Republic of); Yoon, Ho-Geun, E-mail: yhgeun@yuhs.ac [Department of Biochemistry and Molecular Biology, Center for Chronic Metabolic Disease Research, College of Medicine, Yonsei University, Seoul (Korea, Republic of); Brain Korea 21 Project for Medical Sciences, Yonsei University, College of Medicine, Seoul (Korea, Republic of)

2011-07-08

Highlights: {yields} Delphinidin is a novel inhibitor of p300/CBP histone acetyltransferase. {yields} Delphinidin prevents the hyperacetylation of p65 by inhibiting the HAT activity of p300/CBP. {yields} Delphinidin efficiently suppresses the expression of inflammatory cytokines in MH7A cells via hypoacetylation of NF-{kappa}B. {yields} Delphinidin inhibits cytokine release in the Jurkat T lymphocyte cell line. -- Abstract: Histone acetyltransferase (HAT) inhibitors (HATi) isolated from dietary compounds have been shown to suppress inflammatory signaling, which contributes to rheumatoid arthritis. Here, we identified a novel HATi in Punica granatum L. known as delphinidin (DP). DP did not affect the activity of other epigenetic enzymes (histone deacetylase, histone methyltransferase, or sirtuin1). DP specifically inhibited the HAT activities of p300/CBP. It also inhibited p65 acetylation in MH7A cells, a human rheumatoid arthritis synovial cell line. DP-induced hypoacetylation was accompanied by cytosolic accumulation of p65 and nuclear localization of IKB{alpha}. Accordingly, DP treatment inhibited TNF{alpha}-stimulated increases in NF-{kappa}B function and expression of NF-{kappa}B target genes in these cells. Importantly, DP suppressed lipopolysaccharide-induced pro-inflammatory cytokine expression in Jurkat T lymphocytes, demonstrating that HATi efficiently suppresses cytokine-mediated immune responses. Together, these results show that the HATi activity of DP counters anti-inflammatory signaling by blocking p65 acetylation and that this compound may be useful in preventing inflammatory arthritis.

Evaluation of the kappa-opioid receptor-selective tracer [{sup 11}C]GR103545 in awake rhesus macaques

Energy Technology Data Exchange (ETDEWEB)

Schoultz, Bent W. [University of Oslo, Department of Chemistry, Oslo (Norway); Hjornevik, Trine; Willoch, Frode [University of Oslo, Centre for Molecular Biology and Neuroscience and Institute of Basic Medical Sciences, Oslo (Norway); Akershus University Hospital, Department of Nuclear Medicine, Loerenskog (Norway); Marton, Janos [ABX Advanced Biochemical Compounds GmbH, Radeberg (Germany); Noda, Akihiro; Murakami, Yoshihiro; Miyoshi, Sosuke; Nishimura, Shintaro [Medical and Pharmacological Research Center Foundation, Basic Research Department, Hakui City, Ishikawa (Japan); Aarstad, Erik [University College of London, Institute of Nuclear Medicine, London (United Kingdom); Drzezga, Alexander [Technische Universitaet Muenchen, Department of Nuclear Medicine, Klinikum rechts der Isar, Munich (Germany); Matsunari, Ichiro [Medical and Pharmacological Research Center Foundation, Clinical Research Department, Hakui City, Ishikawa (Japan); Henriksen, Gjermund [University of Oslo, Department of Chemistry, Oslo (Norway); Technische Universitaet Muenchen, Department of Nuclear Medicine, Klinikum rechts der Isar, Munich (Germany)

2010-06-15

The recent development in radiosynthesis of the {sup 11}C-carbamate function increases the potential of [{sup 11}C]GR103545, which for the last decade has been regarded as promising for imaging the kappa-opioid receptor ({kappa}-OR) with PET. In the present study, [{sup 11}C]GR103545 was evaluated in awake rhesus macaques. Separate investigations were performed to clarify the OR subtype selectivity of this compound. Regional brain uptake kinetics of [{sup 11}C]GR103545 was studied 0-120 min after injection. The binding affinity and opioid subtype selectivity of [{sup 11}C]GR103545 was determined in cells transfected with cloned human opioid receptors. In vitro binding assays demonstrated a high affinity of GR103545 for {kappa}-OR (K{sub i} = 0.02 {+-}0.01 nM) with excellent selectivity over {mu}-OR (6 x 10{sup 2}-fold) and {delta}-OR (2 x 10{sup 4}-fold). PET imaging revealed a volume of distribution (V{sub T}) pattern consistent with the known distribution of {kappa}-OR, with striatum = temporal cortex > cingulate cortex > frontal cortex > parietal cortex > thalamus > cerebellum. [{sup 11}C]GR103545 is selective for {kappa}-OR and holds promise for use to selectively depict and quantify this receptor in humans by means of PET. (orig.)

Deletion of hepatocyte nuclear factor-1-beta in an infant with prune belly syndrome.

Science.gov (United States)

Haeri, Sina; Devers, Patricia L; Kaiser-Rogers, Kathleen A; Moylan, Vincent J; Torchia, Beth S; Horton, Amanda L; Wolfe, Honor M; Aylsworth, Arthur S

2010-08-01

Prune belly syndrome is a rare congenital disorder characterized by deficiency of abdominal wall muscles, cryptorchidism, and urinary tract anomalies. We have had the opportunity to study a baby with prune belly syndrome associated with an apparently de novo 1.3-megabase interstitial 17q12 microdeletion that includes the hepatocyte nuclear factor-1-beta gene at 17q12. One previous patient, an adult, has been reported with prune belly syndrome and a hepatocyte nuclear factor-1-beta microdeletion. Hepatocyte nuclear factor-1-beta is a widely expressed transcription factor that regulates tissue-specific gene expression and is expressed in numerous tissues including mesonephric duct derivatives, the renal tubule of the metanephros, and the developing prostate of the mouse. Mutations in hepatocyte nuclear factor-1-beta cause the "renal cysts and diabetes syndrome," isolated renal cystic dysplasia, and a variety of other malformations. Based on its expression pattern and the observation of two affected cases, we propose that haploinsufficiency of hepatocyte nuclear factor-1-beta may be causally related to the production of the prune belly syndrome phenotype through a mechanism of prostatic and ureteral hypoplasia that results in severe obstructive uropathy with urinary tract and abdominal distension. Copyright Thieme Medical Publishers.

Measurements of dynamic shape factors of LMFBR aggregate aerosols

International Nuclear Information System (INIS)

Allen, M.D.; Moss, O.R.; Briant, J.K.

1980-01-01

Dynamic shape factors for branched, chain-like aggregates of LMFBR mixed-oxide fuels have been measured with a LAPS spiral-duct centrifuge. The aerosol was generated by repeatedly pulsing a focused laser beam onto the surface of a typical LMFBR fuel pellet. The measured values of the dynamic shape factor, corrected for slip, vary between kappa = 3.60 at D/sub ae/ = 0.5 μm, and kappa = 2.23 at D/sub ae/ = 1.5 μm

Inhibition of nuclear factor kappaB proteins-platinated DNA interactions correlates with cytotoxic effectiveness of the platinum complexes

Czech Academy of Sciences Publication Activity Database

Brabec, Viktor; Kašpárková, Jana; Kostrhunová, Hana; Farrell, N.P.

2016-01-01

Roč. 6, AUG2016 (2016), č. článku 28474. ISSN 2045-2322 R&D Projects: GA MŠk(CZ) LH13096 Institutional support: RVO:68081707 Keywords : interstrand cross-links * group domain proteins Subject RIV: BO - Biophysics Impact factor: 4.259, year: 2016

Binding of kappa- and sigma-opiates in rat brain

International Nuclear Information System (INIS)

Wolozin, B.L.; Nishimura, S.; Pasternak, G.W.

1982-01-01

Detailed displacements of [ 3 H]dihydromorphine by ketocyclazocine and SKF 10,047, [ 3 H]ethylketocyclazocine by SKF 10,047, and [ 3 H]SKF 10,047 by ketocyclazocine are all multiphasic, suggesting multiple binding sites. After treating brain tissue in vitro with naloxazone, all displacements lose the initial inhibition of 3 H-ligand binding by low concentrations of unlabeled drugs. Together with Scatchard analysis of saturation experiments, these studies suggest a common site which binds mu-, kappa, and sigma-opiates and enkephalins equally well and with highest affinity (KD less than 1 nM). The ability of unlabeled drugs to displace the low affinity binding of [ 3 H]dihydromorphine (KD . 3 nM), [ 3 H]ethylketocyclazocine (KD . 4 nM), [ 3 H]SKF 10,047 (KD . 6 nM), and D-Ala2-D-Leu5-[ 3 H]enkephalin (KD . 5 nM) remaining after treating tissue with naloxazone demonstrates unique pharmacological profiles for each. These results suggest the existence of distinct binding sites for kappa- and sigma-opiates which differ from those sites which selectively bind morphine (mu) and enkephalin

Economic benefits of power factor correction at a nuclear facility

International Nuclear Information System (INIS)

Boger, R.M.; Dalos, W.; Juguilon, M.E.

1986-01-01

The economic benefits of correcting poor power factor at an operating nuclear facility are shown. A project approach for achieving rapid return of investment without disrupting plant availability is described. Examples of technical problems associated with using capacitors for power factor correction are presented

Calculating the Unit Cost Factors for Decommissioning Cost Estimation of the Nuclear Research Reactor

International Nuclear Information System (INIS)

Jeong, Kwan Seong; Lee, Dong Gyu; Jung, Chong Hun; Lee, Kune Woo

2006-01-01

The estimated decommissioning cost of nuclear research reactor is calculated by applying a unit cost factor-based engineering cost calculation method on which classification of decommissioning works fitted with the features and specifications of decommissioning objects and establishment of composition factors are based. Decommissioning cost of nuclear research reactor is composed of labor cost, equipment and materials cost. Labor cost of decommissioning costs in decommissioning works are calculated on the basis of working time consumed in decommissioning objects. In this paper, the unit cost factors and work difficulty factors which are needed to calculate the labor cost in estimating decommissioning cost of nuclear research reactor are derived and figured out.

Tungsten phosphanylarylthiolato complexes [W{PhP(2-SC6H4)2-kappa3S,S',P} 2] and [W{P(2-SC6H4)3-kappa4S,S',S",P}2]: synthesis, structures and redox chemistry.

Science.gov (United States)

Hildebrand, Alexandra; Lönnecke, Peter; Silaghi-Dumitrescu, Luminita; Hey-Hawkins, Evamarie

2008-09-14

PhP(2-SHC6H4)2 (PS2H2) reacts with WCl6 with reduction of tungsten to give the air-sensitive tungsten(IV) complex [W{PhP(2-SC6H4)2-kappa(3)S,S',P}2] (1). 1 is oxidised in air to [WO{PhPO(2-SC6H4)2-kappa(3)S,S',O}{PhP(2-SC6H4)2-kappa(3)S,S',P}] (2). The attempted synthesis of 2 by reaction of 1 with iodosobenzene as oxidising agent was unsuccessful. [W{P(2-SC6H4)3-kappa(4)S,S',S",P}2] (3) was formed in the reaction of P(2-SHC6H4)3 (PS3H3) with WCl6. The W(VI) complex 3 contains two PS3(3-) ligands, each coordinated in a tetradentate fashion resulting in a tungsten coordination number of eight. The reaction of 3 with AgBF4 yields the dinuclear tungsten complex [W2{P(2-SC6H4)3-kappa(4)S,S',S",P}3]BF4 (4). Complexes 1-4 were characterised by spectral methods and X-ray structure determination.

The effects of Mucuna pruriens on the renal oxidative stress and transcription factors in high-fructose-fed rats.

Science.gov (United States)

Ulu, Ramazan; Gozel, Nevzat; Tuzcu, Mehmet; Orhan, Cemal; Yiğit, İrem Pembegül; Dogukan, Ayhan; Telceken, Hafize; Üçer, Özlem; Kemeç, Zeki; Kaman, Dilara; Juturu, Vijaya; Sahin, Kazim

2018-05-31

In the present study, we evaluated the effects of M. pruriens administration on metabolic parameters, oxidative stress and kidney nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and nuclear factor (erythroid-derived 2)-like 2 (Nrf2) signaling pathways in high-fructose fed rats. Male rats (n = 28) were divided into 4 groups as control, M. pruriens, fructose, and M. pruriens plus fructose. All rats were fed a standard diet supplemented or no supplemented with M. pruriens (200 mg/kg/d by gavage). Fructose was given in drinking water for 8 weeks. High fructose consumption led to an increase in the serum level of glucose, triglyceride, urea and renal malondialdehyde (MDA) levels. Although M. pruriens treatment reduced triglyceride and MDA levels, it did not affect other parameters. M. pruriens supplementation significantly decreased the expression of NF-ҡB and decreased expression of Nrf2 and HO-1 proteins in the kidney. This study showed that the adverse effects of high fructose were alleviated by M. pruriens supplementation via modulation of the expression of kidney nuclear transcription factors in rats fed high fructose diet. Copyright © 2018 Elsevier Ltd. All rights reserved.

Reciprocal regulation of nuclear factor kappa B and its inhibitor ZAS3 after peripheral nerve injury

Directory of Open Access Journals (Sweden)

Madiai Francesca

2006-01-01

Full Text Available Abstract Background NF-κB binds to the κB motif to regulate transcription of genes involved in growth, immunity and inflammation, and plays a pivotal role in the production of pro-inflammatory cytokines after nerve injuries. The zinc finger protein ZAS3 also binds to the κB or similar motif. In addition to competition for common DNA sites, in vitro experiments have shown that ZAS3 can inhibit NF-κB via the association with TRAF2 to inhibit the nuclear translocation of NF-κB. However, the physiological significance of the ZAS3-mediated inhibition of NF-κB has not been demonstrated. The purpose of this study is to characterize ZAS3 proteins in nervous tissues and to use spinal nerve ligation, a neuropathic pain model, to demonstrate a functional relationship between ZAS3 and NF-κB. Results Immunohistochemical experiments show that ZAS3 is expressed in specific regions of the central and peripheral nervous system. Abundant ZAS3 expression is found in the trigeminal ganglion, hippocampal formation, dorsal root ganglia, and motoneurons. Low levels of ZAS3 expressions are also found in the cerebral cortex and in the grey matter of the spinal cord. In those nervous tissues, ZAS3 is expressed mainly in the cell bodies of neurons and astrocytes. Together with results of Western blot analyses, the data suggest that ZAS3 protein isoforms with differential cellular distribution are produced in a cell-specific manner. Further, neuropathic pain confirmed by persistent mechanical allodynia was manifested in rats seven days after L5 and L6 lumbar spinal nerve ligation. Changes in gene expression, including a decrease in ZAS3 and an increase in the p65 subunit of NF-κB were observed in dorsal root ganglion ipsilateral to the ligation when compared to the contralateral side. Conclusion ZAS3 is expressed in nervous tissues involved in cognitive function and pain modulation. The down-regulation of ZAS3 after peripheral nerve injury may lead to activation of

Dust-acoustic solitons in quantum plasma with kappa-distributed ions

Indian Academy of Sciences (India)

Abstract. Arbitrary amplitude dust-acoustic (DA) solitary waves in an unmagnetized and col- lisionless quantum dusty plasma comprising cold dust particles, kappa (κ)-distributed ions and degenerate electrons are investigated. The influence of suprathermality and quantum effects on the linear dispersion relation of DA ...

An improved Fuzzy Kappa statistic that accounts for spatial autocorrelation

NARCIS (Netherlands)

Hagen - Zanker, A.H.

2009-01-01

The Fuzzy Kappa statistic expresses the agreement between two categorical raster maps. The statistic goes beyond cell-by-cell comparison and gives partial credit to cells based on the categories found in the neighborhood. When matching categories are found at shorter distances the agreement is

Polyphenol Compound as a Transcription Factor Inhibitor.

Science.gov (United States)

Park, Seyeon

2015-10-30

A target-based approach has been used to develop novel drugs in many therapeutic fields. In the final stage of intracellular signaling, transcription factor-DNA interactions are central to most biological processes and therefore represent a large and important class of targets for human therapeutics. Thus, we focused on the idea that the disruption of protein dimers and cognate DNA complexes could impair the transcriptional activation and cell transformation regulated by these proteins. Historically, natural products have been regarded as providing the primary leading compounds capable of modulating protein-protein or protein-DNA interactions. Although their mechanism of action is not fully defined, polyphenols including flavonoids were found to act mostly as site-directed small molecule inhibitors on signaling. There are many reports in the literature of screening initiatives suggesting improved drugs that can modulate the transcription factor interactions responsible for disease. In this review, we focus on polyphenol compound inhibitors against dimeric forms of transcription factor components of intracellular signaling pathways (for instance, c-jun/c-fos (Activator Protein-1; AP-1), c-myc/max, Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and β-catenin/T cell factor (Tcf)).

Human factors in the Canadian nuclear industry: future needs

International Nuclear Information System (INIS)

Harrison, F.

2008-01-01

Currently the industry is facing refurbishment and new builds. At present most licensees in Canada do not have sufficient numbers of Human Factors staff. As a result, the activities of the CNSC are too often focused on providing guidance regarding the application of Human Factors, in addition to reviewing work submitted by the licensee. Greater efficiencies for both the licensee and the CNSC could be realized if licensee staff had greater Human Factors expertise. Strategies for developing Human Factors expertise should be explored through cooperative partnerships with universities, which could be encouraged to include Human Factors courses specific to nuclear. (author)

Factors affecting the next generation of nuclear power

International Nuclear Information System (INIS)

Remick, F.J.

1990-01-01

For both financial, environmental and health reasons, and because of external and internal factors affecting this nation's energy supply, nuclear power will likely play a part in supplying this nation's energy in the coming decades. I believe this to be true for some other parts of the world as well. Even some severe critics of the nuclear power industry and the NRC might agree with me on this point. Increasing concern with the environmental consequences of the burning of fossil fuels has led some former opponents of the use of nuclear power to balance anew the risks and benefits of nuclear power and to modify to some degree their former opposition. A related concern with the adequacy of the energy supply is leading others to modify their positions. According to analyses done by the U.S. Department of Energy, after 1994 the United States will no longer be able to assure all its citizens a reliable supply of electricity. Already, many areas of the country are in need of additional electric capacity. In both Sweden and Switzerland, similar concerns have led to the adoption by many of more compromising positions. Some critics of nuclear power may in the end still reject it as an alternative, but, with the increased pressures on the environment and on our energy supply, nuclear power is an alternative which cannot be rejected without the most serious consideration. This should be, I believe, a point of consensus among us. In sum, there is a future for nuclear power in the sense that there is a use for it

Factors affecting the next generation of nuclear power

Energy Technology Data Exchange (ETDEWEB)

Remick, F J [Nuclear Regulatory Commission, Washington, DC (United States)

1990-07-01

For both financial, environmental and health reasons, and because of external and internal factors affecting this nation's energy supply, nuclear power will likely play a part in supplying this nation's energy in the coming decades. I believe this to be true for some other parts of the world as well. Even some severe critics of the nuclear power industry and the NRC might agree with me on this point. Increasing concern with the environmental consequences of the burning of fossil fuels has led some former opponents of the use of nuclear power to balance anew the risks and benefits of nuclear power and to modify to some degree their former opposition. A related concern with the adequacy of the energy supply is leading others to modify their positions. According to analyses done by the U.S. Department of Energy, after 1994 the United States will no longer be able to assure all its citizens a reliable supply of electricity. Already, many areas of the country are in need of additional electric capacity. In both Sweden and Switzerland, similar concerns have led to the adoption by many of more compromising positions. Some critics of nuclear power may in the end still reject it as an alternative, but, with the increased pressures on the environment and on our energy supply, nuclear power is an alternative which cannot be rejected without the most serious consideration. This should be, I believe, a point of consensus among us. In sum, there is a future for nuclear power in the sense that there is a use for it.

Overall analysis of the cost key factors for the nuclear energy

International Nuclear Information System (INIS)

Caero, M.

1996-01-01

In 1995, 25,8 % of the world electricity consumption was of nuclear origin, while in the EU this figure is increased up to 50,6 %. In order to maintain and even to increase its share in the electricity generation, Nuclear Energy needs to achieve a good economic performance as a base load source when compared with its competitors, basically coal and gas fired plants. Fossil-fired generation costs have declined over the past ten years, mainly due to lower fossil fuel prices. This factor together with the recently observed tendency of higher discount rates to be applied are challenging the attractiveness of the nuclear energy. Nuclear energy is a capital intensive option. Taken into account extensive standardization programs has been established aiming at cost reductions as well as to increase efficiency of nuclear energy utilization, among their main purposes. Externalities play an important role, as they are already internalized in nuclear generation costs. This is not true for many existing coal-fired plants. Even a great uncertainly exists on greenhouse gas effects. Also decisions on greenhouse gas control and their impact on carbonaceous fuel generation costs cannot be clearly predicted, even in the immediate future. Macroeconomic factors like employment, competitiveness, energy conservation, energy availability, energy demand control, etc are positively influenced by the use of nuclear energy. A sustainable economic development cannot be achieved only relying on fossil fuel generation. As a wrap up sustainable development demands nuclear energy in order to cover the future objectives of energy availability, environmental control and energy cost control. (author)

Nuclear-polarization correction to the bound-electron g factor in heavy hydrogenlike ions

OpenAIRE

Nefiodov, A. V.; Plunien, G.; Soff, G.

2002-01-01

The influence of nuclear polarization on the bound-electron $g$ factor in heavy hydrogenlike ions is investigated. Numerical calculations are performed for the K- and L-shell electrons taking into account the dominant virtual nuclear excitations. This determines the ultimate limit for tests of QED utilizing measurements of the bound-electron $g$ factor in highly charged ions.

Nuclear-polarization correction to the bound-electron g factor in heavy hydrogenlike ions.

Science.gov (United States)

Nefiodov, A V; Plunien, G; Soff, G

2002-08-19

The influence of nuclear polarization on the bound-electron g factor in heavy hydrogenlike ions is investigated. Numerical calculations are performed for the K- and L-shell electrons taking into account the dominant virtual nuclear excitations. This determines the ultimate limit for tests of QED utilizing measurements of the bound-electron g factor in highly charged ions.

Firehose constraints of the bi-Kappa-distributed electrons: a zero-order approach for the suprathermal electrons in the solar wind

Czech Academy of Sciences Publication Activity Database

Lazar, M.; Shaaban, S. M.; Poedts, S.; Štverák, Štěpán

2017-01-01

Roč. 464, č. 1 (2017), s. 564-571 ISSN 0035-8711 Institutional support: RVO:68378289 Keywords : instabilities * plasmas * methods * analytical * methods: observational * solar wind Subject RIV: BL - Plasma and Gas Discharge Physics OBOR OECD: Fluids and plasma physics (including surface physics) Impact factor: 4.961, year: 2016 https://academic.oup.com/mnras/article-abstract/464/1/564/2236068/Firehose-constraints-of-the-bi-Kappa-distributed?redirectedFrom=fulltext

Analgesia produced by exposure to 2450-MHz radiofrequency radiation (RFR) is mediated by brain mu- and kappa-opioid receptors

Energy Technology Data Exchange (ETDEWEB)

Salomon, G.; Park, E.J.; Quock, R.M. (Univ. of Illinois, Rockford (United States))

1992-02-26

This study was conducted to identify the opioid receptor subtype(s) responsible for RFR-induced analgesia. Male Swiss Webster mice, 20-25 g, were exposed to 20 mW/cm{sup 2} RFR in a 2,450-MHz waveguide system for 10 min, then tested 15 min later in the abdominal constriction paradigm which detects {mu}- and {kappa}-opioid activity. Immediately following RFR exposure, different groups of mice were pretreated intracerebroventricularly with different opioid receptor blockers with selectivity for {mu}- or {kappa}-opioid receptors. Results show that RFR-induced analgesia was attenuated by higher but not lower doses of the non-selective antagonist naloxone, but the selective {mu}-opioid antagonist {beta}-funaltrexamine and by the selective {kappa}-opioid antagonist norbinaltorphimine. RFR-induced analgesia was also reduced by subcutaneous pretreatment with 5.0 mg/kg of the {mu}-/{kappa}-opioid antagonist({minus})-5,9-diethyl-{alpha}-5,9-dialkyl-2{prime}-hydroxy-6,7-benzomorphan(MR-2266). These findings suggest that RFR-induced analgesia may be mediated by both {mu}- and {kappa}-opioid mechanisms.

The plant limonoid 7-oxo-deacetoxygedunin inhibits RANKL-induced osteoclastogenesis by suppressing activation of the NF-{kappa}B and MAPK pathways

Energy Technology Data Exchange (ETDEWEB)

Wisutsitthiwong, Chonnaree; Buranaruk, Chayanit [Graduate Program in Industrial Microbiology, Department of Microbiology, Faculty of Science, Chulalongkorn University, Phayathai Road, Bangkok 10330 (Thailand); Pudhom, Khanitha [Department of Chemistry, Faculty of Science and Center for Petroleum, Petrochemicals and Advanced Materials, Chulalongkorn University, Phayathai Road, Bangkok 10330 (Thailand); Palaga, Tanapat, E-mail: tanapat.p@chula.ac.th [Graduate Program in Industrial Microbiology, Department of Microbiology, Faculty of Science, Chulalongkorn University, Phayathai Road, Bangkok 10330 (Thailand)

2011-11-18

Highlights: Black-Right-Pointing-Pointer A gedunin type limonoid from seeds of mangroves, 7-oxo-7-deacetoxygedunin, exhibits strong anti-osteoclastogenic activity. Black-Right-Pointing-Pointer Treatment with this limonoid results in significant decrease in expression of NFATc1 and osteoclast-related genes. Black-Right-Pointing-Pointer The mode of action of this limonoid is by inhibiting activation of the NF-{kappa}B and MAPK pathways which are activated by RANKL. -- Abstract: Osteoclasts together with osteoblasts play pivotal roles in bone remodeling. Aberrations in osteoclast differentiation and activity contribute to osteopenic disease. Osteoclasts differentiate from monocyte/macrophage progenitors, a process that is initiated by the interaction between receptor activator of NF-{kappa}B (RANK) and its ligand, RANKL. In this study, we identified 7-oxo-7-deacetoxygedunin (7-OG), a gedunin type limonoid from seeds of the mangrove Xylocarpus moluccensis, as a potent inhibitor of osteoclastogenesis. Additionally, 7-OG showed strong anti-osteoclastogenic activity with low cytotoxicity against the monocyte/macrophage progenitor cell line, RAW264.7. The IC50 for anti-osteoclastogenic activity was 4.14 {mu}M. Treatment with 7-OG completely abolished the appearance of multinucleated giant cells with tartrate-resistant acid phosphatase activity in RAW264.7 cells stimulated with RANKL. When the expression of genes related to osteoclastogenesis was investigated, a complete downregulation of NFATc1 and cathepsin K and a delayed downregulation of irf8 were observed upon 7-OG treatment in the presence of RANKL. Furthermore, treatment with this limonoid suppressed RANKL-induced activation of p38, MAPK and Erk and nuclear localization of NF-{kappa}B p65. Taken together, we present evidence indicating a plant limonoid as a novel osteoclastogenic inhibitor that could be used for osteoporosis and related conditions.

Main factors affecting the fixing work about nuclear engineering and its discussion

International Nuclear Information System (INIS)

Zhang Zhihua; Liu Yaoguan; Qian Dazhi; Liu Hangang; Xu Xianqi; Deng Yue

2010-01-01

Main factors to the impact of the fixing work about nuclear engineering such as project design, construction, plan program, document, preparation, order, locale management, surveillance, quality assurance system and so on were presented. These factors were analyzed and discussed in this paper. Some measures and suggestions were put forward to accelerate construction fixing plan and insure good quality. We wish provide some references and help for someone engaged with construction of nuclear engineering. (authors)

Hantaan Virus Nucleocapsid Protein Binds to Importin alpha Proteins and Inhibits Tumor Necrosis Factor Alpha-Induced Activation of Nuclear Factor Kappa B

Science.gov (United States)

2008-11-19

Microbiology . All Rights Reserved. Hantaan Virus Nucleocapsid Protein Binds to Importin Proteins and Inhibits Tumor Necrosis Factor Alpha-Induced...Division, U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland 21702,1 and Department of Microbiology , Mount Sinai...34–36. 32. Prescott , J., C. Ye, G. Sen, and B. Hjelle. 2005. Induction of innate immune response genes by Sin Nombre hantavirus does not require

Involvement of the nuclear factor-κB signaling pathway in the regulation of CXC chemokine receptor-4 expression in neuroblastoma cells induced by tumor necrosis factor-α.

Science.gov (United States)

Zhi, Yunlai; Lu, Hongting; Duan, Yuhe; Sun, Weisheng; Guan, Ge; Dong, Qian; Yang, Chuanmin

2015-02-01

Metastasis is a hallmark of malignant neuroblastoma and is the main reason for therapeutic failure and recurrence of the tumor. The CXC chemokine receptor-4 (CXCR4), a Gi protein-coupled receptor for the ligand CXCL12/stromal cell-derived factor-1α (SDF-1α), is expressed in various types of tumor. This receptor mediates the homing of tumor cells to specific organs that express the ligand, CXCL12, for this receptor and plays an important role in tumor growth, invasion, metastasis and angiogenesis. In the present study, the inflammatory cytokine, tumor necrosis factor‑α (TNF‑α) upregulated CXCR4 expression in neuroblastoma cells and increased migration to the CXCR4 ligand SDF‑1α. In addition, this effect was dependent upon NF-κB transcriptional activity, as blocking the NF-κB pathway with pyrrolidinedithiocarbamic acid ammonium salt suppressed TNF-α‑induced upregulation of CXCR4 expression and reduced the migration towards the CXCR4 ligand, SDF-1α. Treating neuroblastoma cells with TNF-α resulted in the activation of nuclear factor-kappa B (NF-κB) and subsequently, the translocation of NF-κB from the cytoplasm to the nucleus. Using immunohistochemistry, NF‑κB and CXCR4 were significantly correlated with each other (P=0.0052, Fisher's exact test) in a cohort of neuroblastoma samples (n=80). The present study indicates that the inflammatory cytokine, TNF-α, partially functions through the NF‑κB signaling pathway to upregulate CXCR4 expression to foster neuroblastoma cell metastasis. These findings indicate that effective inhibition of neuroblastoma metastasis should be directed against the inflammatory cytokine-induced NF‑κB/CXCR4/SDF‑1α signaling pathway.

A natural xanthone increases catalase activity but decreases NF-kappa B and lipid peroxidation in U-937 and HepG2 cell lines.

Science.gov (United States)

Sahoo, Binay K; Zaidi, Adeel H; Gupta, Pankaj; Mokhamatam, Raveendra B; Raviprakash, Nune; Mahali, Sidhartha K; Manna, Sunil K

2015-10-05

Mangiferin, a C-glycosyl xanthone, has shown anti-inflammatory, antioxidant, and anti-tumorigenic activities. In the present study, we investigated the molecular mechanism for the antioxidant property of mangiferin. Considering the role of nuclear transcription factor kappa B (NF-κB) in inflammation and tumorigenesis, we hypothesized that modulating its activity will be a viable therapeutic target in regulating the redox-sensitive ailments. Our results show that mangiferin blocks several inducers, such as tumor necrosis factor (TNF), lypopolysaccharide (LPS), phorbol-12-myristate-13-acetate (PMA) or hydrogen peroxide (H2O2) mediated NF-κB activation via inhibition of reactive oxygen species generation. In silico docking studies predicted strong binding energy of mangiferin to the active site of catalase (-9.13 kcal/mol), but not with other oxidases such as myeloperoxidase, glutathione peroxidase, or inducible nitric oxide synthase. Mangiferin increased activity of catalase by 44%, but had no effect on myeloperoxidase activity in vitro. Fluorescence spectroscopy further revealed the binding of mangiferin to catalase at the single site with binding constant and binding affinity of 3.1×10(-7) M(-1) and 1.046 respectively. Mangiferin also inhibits TNF-induced lipid peroxidation and thereby protects apoptosis. Hence, mangiferin with its ability to inhibit NF-κB and increase the catalase activity may prove to be a potent therapeutic. Copyright © 2015 Elsevier B.V. All rights reserved.

Overview of factors affecting the leachability of nuclear waste forms

International Nuclear Information System (INIS)

Stone, J.A.

1980-01-01

An overview of various factors that affect the leachability of nuclear waste forms is presented. The factors affect primarily the leaching system (temperature, for example), the leachant (pH, for example), or the solid being leached (surface condition, for example). A qualitative understanding exists of the major factors affecting leaching, but further studies are needed to establish leaching mechanisms and develop predictive models. 67 refs

Regulation of pri-microRNA BIC transcription and processing in Burkitt lymphoma

NARCIS (Netherlands)

Kluiver, J.; van den Berg, Anke; de Jong, Doetje; Blokzijl, T.; Harms, G.; Bouwman, E.; Jacobs, Susan; Poppema, Sibrand; Kroesen, Bart-Jan

2007-01-01

BIC is a primary microRNA (pri-miR-155) that can be processed to mature miR-155. In this study, we show the crucial involvement of protein kinase C (PKC) and nuclear factor-kappa B (NF-kappa B) in the regulation of BIC expression upon B-cell receptor triggering. Surprisingly, Northern blot analysis

Bortezomib as a new therapeutic approach for blastic plasmacytoid dendritic cell neoplasm.

Science.gov (United States)

Philippe, Laure; Ceroi, Adam; Bôle-Richard, Elodie; Jenvrin, Alizée; Biichle, Sabeha; Perrin, Sophie; Limat, Samuel; Bonnefoy, Francis; Deconinck, Eric; Saas, Philippe; Garnache-Ottou, Francine; Angelot-Delettre, Fanny

2017-11-01

Blastic plasmacytoid dendritic cell neoplasm is an aggressive hematologic malignancy with a poor prognosis. No consensus regarding optimal treatment modalities is currently available. Targeting the nuclear factor-kappa B pathway is considered a promising approach since blastic plasmacytoid dendritic cell neoplasm has been reported to exhibit constitutive activation of this pathway. Moreover, nuclear factor-kappa B inhibition in blastic plasmacytoid dendritic cell neoplasm cell lines, achieved using either an experimental specific inhibitor JSH23 or the clinical drug bortezomib, interferes in vitro with leukemic cell proliferation and survival. Here we extended these data by showing that primary blastic plasmacytoid dendritic cell neoplasm cells from seven patients were sensitive to bortezomib-induced cell death. We confirmed that bortezomib efficiently inhibits the phosphorylation of the RelA nuclear factor-kappa B subunit in blastic plasmacytoid dendritic cell neoplasm cell lines and primary cells from patients in vitro and in vivo in a mouse model. We then demonstrated that bortezomib can be associated with other drugs used in different chemotherapy regimens to improve its impact on leukemic cell death. Indeed, when primary blastic plasmacytoid dendritic cell neoplasm cells from a patient were grafted into mice, bortezomib treatment significantly increased the animals' survival, and was associated with a significant decrease of circulating leukemic cells and RelA nuclear factor-kappa B subunit expression. Overall, our results provide a rationale for the use of bortezomib in combination with other chemotherapy for the treatment of patients with blastic plasmacytoid dendritic cell neoplasm. Based on our data, a prospective clinical trial combining proteasome inhibitor with classical drugs could be envisaged. Copyright© Ferrata Storti Foundation.

Glioma-secreted soluble factors stimulate microglial activation: The role of interleukin-1β and tumor necrosis factor-α.

Science.gov (United States)

Hwang, Ji-Sun; Jung, Eun-Hye; Kwon, Mi-Youn; Han, Inn-Oc

2016-09-15

We aimed to elucidate the effect of soluble factors secreted by glioma on microglial activation. Conditioned medium (CM) from glioma cells, CRT-MG and C6, significantly induced nitric oxide (NO) production and stimulated the mRNA expression of inducible NO synthase (iNOS), interleukin (IL)-1beta, IL-6, tumor necrosis factor-alpha (TNF-α) and cyclooxygenase 2 (COX-2) in BV2 cells. Glioma CM stimulated p38 mitogen-activated protein kinase (MAPK) phosphorylation, and a p38 MAPK inhibitor, SB203580, suppressed CM-induced NO production in BV2 cells. In addition, CM stimulated nuclear factor-kappaB (NF-κB) DNA binding and transcriptional activity, which was repressed by SB203580. Gliomas displayed higher mRNA expression and release of TNF-α and IL-1β than primary astrocyte cells. Neutralization of TNF-α and IL-1β in C6-CM using a neutralizing antibody inhibited NO/iNOS expression in BV-2 cells. These results indicate potential contribution of diffusible tumor-derived factors to regulate microglial activation and subsequent tumor microenvironment. Copyright © 2016. Published by Elsevier B.V.

Basic aspects of tumor cell fatty acid-regulated signaling and transcription factors.

Science.gov (United States)

Comba, Andrea; Lin, Yi-Hui; Eynard, Aldo Renato; Valentich, Mirta Ana; Fernandez-Zapico, Martín Ernesto; Pasqualini, Marìa Eugenia

2011-12-01

This article reviews the current knowledge and experimental research about the mechanisms by which fatty acids and their derivatives control specific gene expression involved during carcinogenesis. Changes in dietary fatty acids, specifically the polyunsaturated fatty acids of the ω-3 and ω-6 families and some derived eicosanoids from lipoxygenases, cyclooxygenases, and cytochrome P-450, seem to control the activity of transcription factor families involved in cancer cell proliferation or cell death. Their regulation may be carried out either through direct binding to DNA as peroxisome proliferator-activated receptors or via modulation in an indirect manner of signaling pathway molecules (e.g., protein kinase C) and other transcription factors (nuclear factor kappa B and sterol regulatory element binding protein). Knowledge of the mechanisms by which fatty acids control specific gene expression may identify important risk factors for cancer and provide insight into the development of new therapeutic strategies for a better management of whole body lipid metabolism.

The human factor in the organisation and regulation of nuclear safety

International Nuclear Information System (INIS)

Bordes, F.; Savagner, J.-M.; Snanoudj, G.

1981-10-01

The TMI accident has brought to light the importance of the human factor in the safe operation of complex installations such as nuclear power plants. On this basis, the paper outlines the institutional framework for nuclear safety in France and reports on EDF practices in human resources management as well as in the improvement of working premises (control rooms) to optimize human behaviour in accident conditions. Finally, the interaction of labour laws on nuclear law in connection with safety is described. (NEA) [fr

Immunodeficiency associated with a nonsense mutation of IKBKB

DEFF Research Database (Denmark)

Nielsen, Christian; Jakobsen, Marianne A; Larsen, Martin Jakob

2014-01-01

We report an infant of consanguineous parents of Turkish decent with a novel immunodeficiency associated with homozygosity for a nonsense mutation of the gene encoding Inhibitor of nuclear factor kappa-B (NF-κB) kinase subunit beta (IKKβ). At five months, she presented with respiratory insufficie......We report an infant of consanguineous parents of Turkish decent with a novel immunodeficiency associated with homozygosity for a nonsense mutation of the gene encoding Inhibitor of nuclear factor kappa-B (NF-κB) kinase subunit beta (IKKβ). At five months, she presented with respiratory...... no explanation before whole exome sequencing revealed a novel mutation abrogating signaling through the canonical NF-κB pathway....

Effects of the kappa opioid receptor antagonist MR-2266-BS on the acquisition of ethanol preference

Energy Technology Data Exchange (ETDEWEB)

Sandi, C.; Borrell, J.; Guaza, C. (Cajal Institute, Madrid (Spain))

1990-01-01

Using a paradigm by which rats forced to drink a weak ethanol solution develop ethanol preference in consecutive retention testing days, the effects of the administration of the kappa opioid antagonist MR-2266-BS, prior to or after the forced ethanol session, were studied. Pre-conditioning subcutaneous (s.c.) administration of 1 mg/kg of MR-2266-BS induced a decrease in subsequent ethanol consumption without significantly modifying the acquisition of ethanol preference. Post-conditioning administration of MR-2266-BS induced both a dose-dependent reduction in ethanol consumption and in preference throughout the three following days. The results of the present study provide further support of the involvement of kappa-type opioids on drinking behavior, and suggest that kappa receptors may be involved in the consumption and development of preference to ethanol.

A Study on the Allowable Safety Factor of Cut-Slopes for Nuclear Facilities

Energy Technology Data Exchange (ETDEWEB)

Kim, Myung Soo; Yee, Eric [KEPCO International Nuclear Graduate School, Ulsan (Korea, Republic of)

2015-10-15

In this study, the issues of allowable safety factor design criteria for cut-slopes in nuclear facilities is derived through case analysis, a proposed construction work slope design criteria that provides relatively detailed conditions can be applied in case of the dry season and some unclear parts of slope design criteria be modified in case of the rainy season. This safety factor can be further subdivided into two; normal and earthquake factors, a factor of 1.5 is applied for normal conditions and a factor of 1.2 is applied for seismic conditions. This safety factor takes into consideration the effect of ground water and rainfall conditions. However, no criteria for the case of cut-slope in nuclear facilities and its response to seismic conditions is clearly defined, this can cause uncertainty in design. Therefore, this paper investigates the allowable safety factor for cut-slopes in nuclear facilities, reviews conditions of both local and international cut-slope models and finally suggests an alternative method of analysis. It is expected that the new design criteria adequately ensures the stability of the cut-slope to reflect clear conditions for both the supervising and design engineers.

Factor analysis for the adoption of nuclear technology in diagnosis and treatment of chronic diseases

International Nuclear Information System (INIS)

Sato, Renato Cesar; Zouain, Desiree Moraes

2012-01-01

To identify and evaluate latent variables (variables that are not directly observed) for adopting and using nuclear technologies in diagnosis and treatment of chronic diseases. The measurement and management of these latent factors are important for health care due to complexities of the sector. Methods: An exploratory factor analysis study was conducted among 52 physicians practicing in the areas of Cardiology, Neurology and Oncology in the State of Sao Paulo who agreed to participate in the study between 2009 and 2010. Data were collected using an attitude measurement questionnaire, and analyzed according to the principal component method with Varimax rotation. Results: The component matrix after factor rotation showed three elucidative groups arranged according to demand for nuclear technology: clinical factors, structural factors, and technological factors. Clinical factors included questionnaire answers referring to medical history, previous interventions, complexity and chronicity of the disease. Structural factors included patient age, physician's practice area, and payment ability. Technological factors included prospective growth in the use of nuclear technology and availability of services. Conclusions: The clinical factors group dimension identified in the study included patient history, prior interventions, and complexity and chronicity of the disease. This dimension is the main motivating for adopting nuclear technology in diagnosis and treatment of chronic diseases. (author)

Polyphenol Compound as a Transcription Factor Inhibitor

Directory of Open Access Journals (Sweden)

Seyeon Park

2015-10-01

Full Text Available A target-based approach has been used to develop novel drugs in many therapeutic fields. In the final stage of intracellular signaling, transcription factor–DNA interactions are central to most biological processes and therefore represent a large and important class of targets for human therapeutics. Thus, we focused on the idea that the disruption of protein dimers and cognate DNA complexes could impair the transcriptional activation and cell transformation regulated by these proteins. Historically, natural products have been regarded as providing the primary leading compounds capable of modulating protein–protein or protein-DNA interactions. Although their mechanism of action is not fully defined, polyphenols including flavonoids were found to act mostly as site-directed small molecule inhibitors on signaling. There are many reports in the literature of screening initiatives suggesting improved drugs that can modulate the transcription factor interactions responsible for disease. In this review, we focus on polyphenol compound inhibitors against dimeric forms of transcription factor components of intracellular signaling pathways (for instance, c-jun/c-fos (Activator Protein-1; AP-1, c-myc/max, Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB and β-catenin/T cell factor (Tcf.

Human factor engineering applied to nuclear power plant design

International Nuclear Information System (INIS)

Manrique, A.; Valdivia, J.C.

2007-01-01

Advantages of implementing adequate Human Factor Engineering techniques in the design of nuclear reactors have become not only a fact recognized by the majority of engineers and operators but also an explicit requirement regulated and mandatory for the new designs of the so called advanced reactors. The first step for this is preparing a plan to incorporate all the Human Factor Engineering principles and developing an integral design of the Instrumentation and Control and Man-machine interface systems. Such a plan should state: -) Activities to be performed, and -) Creation of a Human Factor Engineering team adequately qualified. The Human Factor Engineering team is an integral part of the design team and is strongly linked to the engineering organizations but simultaneously has independence to act and is free to evaluate designs and propose changes in order to enhance human behavior. TECNATOM S.A. (a Spanish company) has been a part of the Design and Human Factor Engineering Team and has collaborated in the design of an advanced Nuclear Power Plant, developing methodologies and further implementing those methodologies in the design of the plant systems through the development of the plant systems operational analysis and of the man-machine interface design. The methodologies developed are made up of the following plans: -) Human Factor Engineering implementation in the Man-Machine Interface design; -) Plant System Functional Requirement Analysis; -) Allocation of Functions to man/machine; -) Task Analysis; -) Human-System Interface design; -) Control Room Verification and -) Validation

Human factor in the problem of Russian nuclear industry safety

International Nuclear Information System (INIS)

Abramova, V.

2002-01-01

The approach to human factor definition, considered in the paper, consists of recognition of as many as possible factors for developing a complete list of factors, which have influence on mistakes or successful work of NPP personnel. Safety culture is considered as the main factor. The enhancement in nuclear power industry includes an optimization of organizational structures and development of personnel safety attitudes. The organizational factors, as possible root causes for human errors, need to be identified, assessed and improved. The organizational activities taken in Russia are presented

Organisational factors. Their definition and influence on nuclear safety. Final report

International Nuclear Information System (INIS)

Baumont, G.; Wahlstroem, B.; Sola, R.; Williams, J.; Frischknecht, A.; Wilpert, B.; Rollenhagen, C.

2000-12-01

The importance of organisational factors in the operational safety and efficiency of nuclear power plants (NPP) has been recognised by many organisations around the world. Despite this recognition, however, there are as yet very few methods by which organisational factors can be systematically assessed and improved. The majority of research efforts applied so far have tended to be modest and scattered. The ORFA project was created as a remedy to these problems. The objective of the project is to create a better understanding of how organisation and management factors influence nuclear safety. A key scientific objective of the project is to identify components of a theoretical framework, which would help in understanding the relationships between organisational factors and nuclear safety. Three work packages were planned. First, a review of literature listed out the identified factors and methods for assessing them. Then, a draft version of the present report was prepared to clarify the environment context and the main issues of the topics. This draft was discussed at the ORFA seminar in Madrid 21-22 October 1999. During the seminar views and comments were collected on preliminary results of the project. Finally, this information has been integrated in the present and other reports and will be used to give further guidance to the European Commission in the development of forthcoming research programmes in the field. The project has addressed nuclear safety taking a broad perspective, which reflected and took into account the views of senior NPP management and regulators. The questions discussed during the project have been: how can organisational factors be included in safety assessments, how can good and bad operational practices be identified, which methods can be used for detecting weak signals of deteriorating performance, how should incidents be analysed with respect to organisational factors to give the largest learning benefit, how can data on organisational

Discussion on verification criterion and method of human factors engineering for nuclear power plant controller

International Nuclear Information System (INIS)

Yang Hualong; Liu Yanzi; Jia Ming; Huang Weijun

2014-01-01

In order to prevent or reduce human error and ensure the safe operation of nuclear power plants, control device should be verified from the perspective of human factors engineering (HFE). The domestic and international human factors engineering guidelines about nuclear power plant controller were considered, the verification criterion and method of human factors engineering for nuclear power plant controller were discussed and the application examples were provided for reference in this paper. The results show that the appropriate verification criterion and method should be selected to ensure the objectivity and accuracy of the conclusion. (authors)

Ordovician and Silurian Phi Kappa and Trail Creek formations, Pioneer Mountains, central Idaho; stratigraphic and structural revisions, and new data on graptolite faunas

Science.gov (United States)

Dover, James H.; Berry, William B.N.; Ross, Reuben James

1980-01-01

Recent geologic mapping in the northern Pioneer Mountains combined with the identification of graptolites from 116 new collections indicate that the Ordovician and Silurian Phi Kappa and Trail Creek Formations occur in a series of thrust-bounded slices within a broad zone of imbricate thrust faulting. Though confirming a deformational style first reported in a 1963 study by Michael Churkin, our data suggest that the complexity and regional extent of the thrust zone were not previously recognized. Most previously published sections of the Phi Kappa and Trail Creek Formations were measured across unrecognized thrust faults and therefore include not only structural repetitions of graptolitic Ordovician and Silurian rocks but also other tectonically juxtaposed lithostratigraphic units of diverse ages as well. Because of this discovery, the need to reconsider the stratigraphic validity of these formations and their lithology, nomenclature, structural distribution, facies relations, and graptolite faunas has arisen. The Phi Kappa Formation in most thrust slices has internal stratigraphic continuity despite the intensity of deformation to which it was subjected. As revised herein, the Phi Kappa Formation is restricted to a structurally repeated succession of predominantly black, carbonaceous, graptolitic argillite and shale. Some limy, light-gray-weathering shale occurs in the middle part of the section, and fine-grained locally pebbly quartzite is present at the base. The basal quartzite is here named the Basin Gulch Quartzite Member of the Phi Kappa. The Phi Kappa redefined on a lithologic basis represents the span of Ordovician time from W. B. N. Berry's graptolite zones 2-4 through 15 and also includes approximately 17 m of lithologically identical shale of Early and Middle Silurian age at the top. The lower contact of the formation as revised is tectonic. The Phi Kappa is gradationally overlain by the Trail Creek Formation as restricted herein. Most of the coarser

Hepatoprotective Effect of Quercetin on Endoplasmic Reticulum Stress and Inflammation after Intense Exercise in Mice through Phosphoinositide 3-Kinase and Nuclear Factor-Kappa B

Directory of Open Access Journals (Sweden)

Yuhan Tang

2016-01-01

Full Text Available The mechanisms underlying intense exercise-induced liver damage and its potential treatments remain unclear. We explored the hepatoprotection and mechanisms of quercetin, a naturally occurring flavonoid, in strenuous exercise-derived endoplasmic reticulum stress (ERS and inflammation. Intense exercise (28 m/min at a 5° slope for 90 min resulted in the leakage of aminotransferases in the BALB/C mice. The hepatic ultrastructural malformations and oxidative stress levels were attenuated by quercetin (100 mg/kg·bw. Intense exercise and thapsigargin- (Tg- induced ERS (glucose-regulated protein 78, GRP78 and inflammatory cytokines levels (IL-6 and TNF-α were decreased with quercetin. Furthermore, quercetin resulted in phosphoinositide 3-kinase (PI3K induction, Ca2+ restoration, and blockade of the activities of Jun N-terminal kinase (JNK, activating transcription factor 6 (ATF6 and especially NF-κB (p65 and p50 nuclear translocation. A PI3K inhibitor abrogated the protection of quercetin on ERS and inflammation of mouse hepatocytes. SP600125 (JNK inhibitor, AEBSF (ATF6 inhibitor, and especially PDTC (NF-κB inhibitor enhanced the quercetin-induced protection against Tg stimulation. Collectively, intense exercise-induced ERS and inflammation were attenuated by quercetin. PI3K/Akt activation and JNK, ATF6, and especially NF-κB suppression were involved in the protection. Our results highlight a novel preventive strategy for treating ERS and inflammation-mediated liver damage induced by intense exercise using natural phytochemicals.

Behavioral meaningful opioidergic stimulation activates kappa receptor gene expression

International Nuclear Information System (INIS)

Teodorov, E.; Ferrari, M.F.R.; Fior-Chadi, D.R.; Camarini, R.; Felício, L.F.

2012-01-01

The periaqueductal gray (PAG) has been reported to be a location for opioid regulation of pain and a potential site for behavioral selection in females. Opioid-mediated behavioral and physiological responses differ according to the activity of opioid receptor subtypes. The present study investigated the effects of the peripheral injection of the kappa-opioid receptor agonist U69593 into the dorsal subcutaneous region of animals on maternal behavior and on Oprk1 gene activity in the PAG of female rats. Female Wistar rats weighing 200-250 g at the beginning of the study were randomly divided into 2 groups for maternal behavior and gene expression experiments. On day 5, pups were removed at 7:00 am and placed in another home cage that was distant from their mother. Thirty minutes after removing the pups, the dams were treated with U69593 (0.15 mg/kg, sc) or 0.9% saline (up to 1 mL/kg) and after 30 min were evaluated in the maternal behavior test. Latencies in seconds for pup retrieval, grouping, crouching, and full maternal behavior were scored. The results showed that U69593 administration inhibited maternal behavior (P < 0.05) because a lower percentage of U69593 group dams showed retrieval of first pup, retrieving all pups, grouping, crouching and displaying full maternal behavior compared to the saline group. Opioid gene expression was evaluated using real-time reverse-transcription polymerase chain reaction (RT-PCR). A single injection of U69593 increased Oprk1 PAG expression in both virgin (P < 0.05) and lactating female rats (P < 0.01), with no significant effect on Oprm1 or Oprd1 gene activity. Thus, the expression of kappa-opioid receptors in the PAG may be modulated by single opioid receptor stimulation and behavioral meaningful opioidergic transmission in the adult female might occur simultaneously to specific changes in gene expression of kappa-opioid receptor subtype. This is yet another alert for the complex role of the opioid system in female

Behavioral meaningful opioidergic stimulation activates kappa receptor gene expression

Energy Technology Data Exchange (ETDEWEB)

Teodorov, E. [Centro de Matemática, Computação e Cognição, Universidade Federal do ABC, São Paulo, SP (Brazil); Ferrari, M.F.R. [Departamento de Genética e Biologia Evolutiva, Instituto de Biociências, Universidade de São Paulo, São Paulo, SP (Brazil); Fior-Chadi, D.R. [Departamento de Fisiologia, Instituto de Biociências, Universidade de São Paulo, São Paulo, SP (Brazil); Camarini, R. [Departamento de Farmacologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP (Brazil); Felício, L.F. [Departamento de Patologia, Faculdade de Medicina Veterinária e Zootecnia, Universidade de São Paulo, São Paulo, SP (Brazil)

2012-06-01

The periaqueductal gray (PAG) has been reported to be a location for opioid regulation of pain and a potential site for behavioral selection in females. Opioid-mediated behavioral and physiological responses differ according to the activity of opioid receptor subtypes. The present study investigated the effects of the peripheral injection of the kappa-opioid receptor agonist U69593 into the dorsal subcutaneous region of animals on maternal behavior and on Oprk1 gene activity in the PAG of female rats. Female Wistar rats weighing 200-250 g at the beginning of the study were randomly divided into 2 groups for maternal behavior and gene expression experiments. On day 5, pups were removed at 7:00 am and placed in another home cage that was distant from their mother. Thirty minutes after removing the pups, the dams were treated with U69593 (0.15 mg/kg, sc) or 0.9% saline (up to 1 mL/kg) and after 30 min were evaluated in the maternal behavior test. Latencies in seconds for pup retrieval, grouping, crouching, and full maternal behavior were scored. The results showed that U69593 administration inhibited maternal behavior (P < 0.05) because a lower percentage of U69593 group dams showed retrieval of first pup, retrieving all pups, grouping, crouching and displaying full maternal behavior compared to the saline group. Opioid gene expression was evaluated using real-time reverse-transcription polymerase chain reaction (RT-PCR). A single injection of U69593 increased Oprk1 PAG expression in both virgin (P < 0.05) and lactating female rats (P < 0.01), with no significant effect on Oprm1 or Oprd1 gene activity. Thus, the expression of kappa-opioid receptors in the PAG may be modulated by single opioid receptor stimulation and behavioral meaningful opioidergic transmission in the adult female might occur simultaneously to specific changes in gene expression of kappa-opioid receptor subtype. This is yet another alert for the complex role of the opioid system in female

Absence of prognostic value of nuclear shape factor analysis in colorectal carcinoma: relevance of interobserver and intraobserver variability.

Science.gov (United States)

Di Fabio, Francesco; Shrier, Ian; Bégin, Louis R; Gordon, Philip H

2008-12-01

Several retrospective studies, including our previous investigation, have shown a prognostic value of nuclear shape factor in colorectal carcinomas. This prospective study was designed to assess the reliability of nuclear shape factor determined by nuclear morphometry and to confirm its prognostic value. Ninety-eight patients who underwent colorectal carcinoma resection were prospectively enrolled. Measurement of nuclear shape factor was performed by using a computer-based image analysis system. Nuclear shape factor was defined as the degree of circularity of the nucleus (1.0 for a perfect circle and values by American Joint Committee on Cancer stage were: 0.73 (0.07) in Stage I, 0.74 (0.06) in Stage II, and 0.75 (0.05) in Stage III carcinomas (P = 0.78, ANOVA). The intraobserver agreement was poor for observer A (r = 0.28) and practically nonexistent for observer B (r = -0.004, Pearson correlation). The intraclass coefficient for interobserver agreement was practically nonexistent. No significant association between nuclear shape factor and ten-year survival was found. Our prospective results, as opposed to our previous retrospective results, suggest that the reliability for nuclear shape factor morphometric analysis is very poor. We failed to confirm a prognostic value for nuclear shape factor in colorectal carcinoma.

Evidence for site-specific occupancy of the mitochondrial genome by nuclear transcription factors.

Directory of Open Access Journals (Sweden)

Georgi K Marinov

Full Text Available Mitochondria contain their own circular genome, with mitochondria-specific transcription and replication systems and corresponding regulatory proteins. All of these proteins are encoded in the nuclear genome and are post-translationally imported into mitochondria. In addition, several nuclear transcription factors have been reported to act in mitochondria, but there has been no comprehensive mapping of their occupancy patterns and it is not clear how many other factors may also be found in mitochondria. Here we address these questions by using ChIP-seq data from the ENCODE, mouseENCODE and modENCODE consortia for 151 human, 31 mouse and 35 C. elegans factors. We identified 8 human and 3 mouse transcription factors with strong localized enrichment over the mitochondrial genome that was usually associated with the corresponding recognition sequence motif. Notably, these sites of occupancy are often the sites with highest ChIP-seq signal intensity within both the nuclear and mitochondrial genomes and are thus best explained as true binding events to mitochondrial DNA, which exist in high copy number in each cell. We corroborated these findings by immunocytochemical staining evidence for mitochondrial localization. However, we were unable to find clear evidence for mitochondrial binding in ENCODE and other publicly available ChIP-seq data for most factors previously reported to localize there. As the first global analysis of nuclear transcription factors binding in mitochondria, this work opens the door to future studies that probe the functional significance of the phenomenon.

Localized Gastric Amyloidosis with Kappa and Lambda Light Chain Co-Expression

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Yong Hwan Ahn

2018-05-01

Full Text Available Esophagogastroduodenoscopy for cancer screening was performed in a 55-year-old woman as part of a health screening program, and revealed a depressed lesion approximately 20 mm in diameter in the lesser curvature of the mid-gastric body. Several biopsy specimens were collected as the lesion resembled early gastric cancer; however, histopathologic evaluation revealed chronic active gastritis with an ulcer and amorphous eosinophilic material deposition. Congo red staining identified amyloid proteins, and apple-green birefringence was shown using polarized light microscopy. Immunohistochemical staining revealed the presence of kappa and lambda chain-positive plasma cells. There was no evidence of underlying plasma cell dyscrasia or amyloid deposition in other segments of the gastrointestinal tract. Echocardiography and computed tomography of the chest, abdomen, and pelvis did not show any significant findings. Thus, the patient was diagnosed with localized gastric amyloidosis with kappa and lambda light chain coexpression.

Synergistic nuclear import of NeuroD1 and its partner transcription factor, E47, via heterodimerization

International Nuclear Information System (INIS)

Mehmood, Rashid; Yasuhara, Noriko; Oe, Souichi; Nagai, Masahiro; Yoneda, Yoshihiro

2009-01-01

The transition from undifferentiated pluripotent cells to terminally differentiated neurons is coordinated by a repertoire of transcription factors. NeuroD1 is a type II basic helix loop helix (bHLH) transcription factor that plays critical roles in neuronal differentiation and maintenance in the central nervous system. Its dimerization with E47, a type I bHLH transcription factor, leads to the transcriptional regulation of target genes. Mounting evidence suggests that regulating the localization of transcription factors contributes to the regulation of their activity during development as defects in their localization underlie a variety of developmental disorders. In this study, we attempted to understand the nuclear import mannerisms of NeuroD1 and E47. We found that the nuclear import of NeuroD1 and E47 is energy-dependent and involves the Ran-mediated pathway. Herein, we demonstrate that NeuroD1 and E47 can dimerize inside the cytoplasm before their nuclear import. Moreover, this dimerization promotes nuclear import as the nuclear accumulation of NeuroD1 was enhanced in the presence of E47 in an in vitro nuclear import assay, and NLS-deficient NeuroD1 was successfully imported into the nucleus upon E47 overexpression. NeuroD1 also had a similar effect on the nuclear accumulation of NLS-deficient E47. These findings suggest a novel role for dimerization that may promote, at least partially, the nuclear import of transcription factors allowing them to function efficiently in the nucleus.

Differential regulation of. mu. , delta, kappa opioid receptors by Mn/sup + +/

Energy Technology Data Exchange (ETDEWEB)

Szuecs, M.; Oetting, G.M.; Coscia, C.J.

1986-03-05

Differential effects of Mn/sup + +/ on three opioid receptor subtypes of rat brain membranes were evaluated. Concentration dependency studies performed with 0.05-20 mM Mn/sup + +/ revealed that only the delta receptors are stimulated at any concentration. The binding of 1 nM /sup 3/H-DAGO was not stimulated by low concentrations (< 1mM) of Mn/sup + +/, and was significantly inhibited at higher concentrations (40% at 20 mM). 1 nM /sup 3/H-EKC (+100nM DAGO and 100nM DADLE) binding was inhibited by Mn/sup + +/ in the entire concentration range. While regulation of ..mu.. receptor binding did not change during postnatal development, delta and kappa binding displayed a pronounced developmental time-dependency. Kappa sites were hardly affected by Mn/sup + +/ at day 5, and adult levels of inhibition were reached only after the third week postnatal. In contrast, 1 nM /sup 3/H-DADLE (+10nM DAGO) binding was most sensitive to Mn/sup + +/ on day 5 after birth (100% stimulation with 5-20 mM). The ED/sub 50/ of Mn/sup + +/ stimulation was unchanged during maturation. These immature delta sites displayed a similar extent of Mn/sup + +/ reversal of Gpp(NH)p inhibition as seen in microsomes, which represent a good model of N/sub i/-uncoupled receptors. These data suggest that ..mu.., delta and kappa receptors are differently coupled to N/sub i/. Moreover, a second divalent cation binding site, in addition to that on N/sub i/ might exist for delta receptors.

Regression analysis of nuclear plant capacity factors

International Nuclear Information System (INIS)

Stocks, K.J.; Faulkner, J.I.

1980-07-01

Operating data on all commercial nuclear power plants of the PWR, HWR, BWR and GCR types in the Western World are analysed statistically to determine whether the explanatory variables size, year of operation, vintage and reactor supplier are significant in accounting for the variation in capacity factor. The results are compared with a number of previous studies which analysed only United States reactors. The possibility of specification errors affecting the results is also examined. Although, in general, the variables considered are statistically significant, they explain only a small portion of the variation in the capacity factor. The equations thus obtained should certainly not be used to predict the lifetime performance of future large reactors

Psychological factors affecting public acceptance of nuclear energy. Comparative analysis focusing on regional characteristics and degree of knowledge

International Nuclear Information System (INIS)

Kimura, Hiroshi; Suzuki, Atsuyuki; Furuta, Kazuo

2003-01-01

The purpose of this research is to clarify how psychological factors' impact on public acceptance of nuclear energy varies with where they live and their degree of knowledge. For this purpose, we carried out questionnaire survey about nuclear energy at three urban areas and two nuclear power plant siting areas. After collecting data, we applied factor analysis to the data, and found four factors which construct cognitive structure of nuclear energy. Using multiple regression analysis, we evaluated the impact of the four factors on two issues: the decision for or against nuclear policy and the reaction to nuclear power plant siting, and compared changes of the impact by where respondents live and their degree of knowledge. Consequently, we found that the impact of all four factors on the two issues varies with where respondents live. We also found that the impact of respondents' degree of knowledge to four factors varies with where they live. (author)

Koefesien Kappa sebagai Indeks Kesepakatan Hasil Diognosis Mikroskopis Malaria di Kabupaten Belu Nusa Tenggara Timur

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Fridolina Mau

2015-07-01

Full Text Available AbstractBlood slide examination is used as standard malaria diagnosis in Indonesia. Quality assurance for malaria microscopic examination is an important issue in the monitoring and supervision of the administration of antimalarials drugs. This step was done to determine the accuracy of thediagnosis, thus could be used for further evaluation in improving the skills of microscopic health centre personnel. This study aims to determine the accuracy of malaria microscopic examination at Primary health centre and District Health Office personnels in Belu District, Nusa Tenggara Timur.The study was an observational research with cross sectional approach. The competency of primary health center and district healt office microscopist in examining malaria blood smears were evaluated using standard blood smears compared with smears from Passive Case Detection (PCD activities. Performance in preparing blood smear were evaluatied by observation and filling the checklist. The study was conducted in April - Juni 2012 in Belu District, NTT. Quality assurance was assessed based on the results of cross-checking and assessments of Kappa coefficient between primary health centre and district Health office microscopic personnel and those between district health centers and Department of parasitology, faculty of Medicine, (Gadjah Mada University certified microscopicpersonnel. Result shows that the strength of agreement between the Primary Health Centre and the District Health Office microscopic personnel centers was "good" (kappa 0.61 to 0.80, while those between District Health Office and Department of Parasitology UGM showed poor agreement (0,20– 0,40Keywords : microscopic examination of malaria, Belu District, cross check, KappaAbstrakPemeriksaan sediaan darah masih merupakan baku emas penegakan diagnosis malaria di Indonesia. Pemantapan kualitas mikroskopis malaria merupakan hal penting dalam pemantauan dan pengawasan pemberian obat anti malaria yang tepat

Human factors methods for nuclear control room design. Volume I. Human factors enhancement of existing nuclear control rooms. Final report

International Nuclear Information System (INIS)

Seminara, J.L.; Seidenstein, S.; Eckert, S.K.; Smith, D.L.

1979-11-01

Human factors engineering is an interdisciplinary specialty concerned with influencing the design of equipment systems, facilities, and operational environments to promote safe, efficient, and reliable operator performance. Human factors approaches were applied in the design of representative nuclear power plant control panels. First, methods for upgrading existing operational control panels were examined. Then, based on detailed human factors analyses of operator information and control requirements, designs of reactor, feedwater, and turbine-generator control panels were developed to improve the operator-control board interface, thereby reducing the potential for operator errors. In addition to examining present-generation concepts, human factors aspects of advanced systems and of hybrid combinations of advanced and conventional designs were investigated. Special attention was given to warning system designs. Also, a survey was conducted among control board designers to (1) develop an overview of design practices in the industry, and (2) establish appropriate measures leading to a more systematic concern for human factors in control board design

Organizational factors and nuclear power plant safety

International Nuclear Information System (INIS)

Haber, S.B.

1995-01-01

There are many organizations in our society that depend on human performance to avoid incidents involving significant adverse consequences. As our culture and technology have become more sophisticated, the management of risk on a broad basis has become more and more critical. The safe operation of military facilities, chemical plants, airlines, and mass transit, to name a few, are substantially dependent on the performance of the organizations that operate those facilities. The nuclear power industry has, within the past 15 years, increased the attention given to the influence of human performance in the safe operation of nuclear power plants (NPP). While NPPs have been designed through engineering disciplines to intercept and mitigate events that could cause adverse consequences, it has been clear from various safety-related incidents that human performance also plays a dominant role in preventing accidents. Initial efforts following the 1979 Three Mile Island incident focused primarily on ergonomic factors (e.g., the best design of control rooms for maximum performance). Greater attention was subsequently directed towards cognitive processes involved in the use of NPP decision support systems and decision making in general, personnel functions such as selection systems, and the influence of work scheduling and planning on employees' performance. Although each of these approaches has contributed to increasing the safety of NPPS, during the last few years, there has been a growing awareness that particular attention must be paid to how organizational processes affect NPP personnel performance, and thus, plant safety. The direct importance of organizational factors on safety performance in the NPP has been well-documented in the reports on the Three Mile Island and Chernobyl accidents as well as numerous other events, especially as evaluated by the U.S. Nuclear Regulatory Commission (NRC)

Rel/Nuclear factor-kappa B apoptosis pathways in human cervical cancer cells

Science.gov (United States)

Shehata, Marlene F

2005-01-01

Cervical cancer is considered a common yet preventable cause of death in women. It has been estimated that about 420 women out of the 1400 women diagnosed with cervical cancer will die during 5 years from diagnosis. This review addresses the pathogenesis of cervical cancer in humans with a special emphasis on the human papilloma virus as a predominant cause of cervical cancer in humans. The current understanding of apoptosis and regulators of apoptosis as well as their implication in carcinogenesis will follow. A special focus will be given to the role of Rel/NF-κB family of genes in the growth and chemotherapeutic treatment of the malignant HeLa cervical cells emphasizing on Xrel3, a cRel homologue. PMID:15857509

$\\kappa$-Minkowski star product in any dimension from symplectic realization

OpenAIRE

Pachol, Anna; Vitale, Patrizia

2015-01-01

We derive an explicit expression for the star product reproducing the $\\kappa$-Minkowski Lie algebra in any dimension $n$. The result is obtained by suitably reducing the Wick-Voros star product defined on $\\mathbb{C}^{d}_\\theta$ with $n=d+1$. It is thus shown that the new star product can be obtained from a Jordanian twist.

Korteweg-deVries-Burgers (KdVB) equation in a five component cometary plasma with kappa described electrons and ions

Science.gov (United States)

Michael, Manesh; Willington, Neethu T.; Jayakumar, Neethu; Sebastian, Sijo; Sreekala, G.; Venugopal, Chandu

2016-12-01

We investigate the existence of ion-acoustic shock waves in a five component cometary plasma consisting of positively and negatively charged oxygen ions, kappa described hydrogen ions, hot solar electrons, and slightly colder cometary electrons. The KdVB equation has been derived for the system, and its solution plotted for different kappa values, oxygen ion densities, as well as the temperature ratios for the ions. It is found that the amplitude of the shock wave decreases with increasing kappa values. The strength of the shock profile decreases with increasing temperatures of the positively charged oxygen ions and densities of negatively charged oxygen ions.

Study of greenhouse gases emission factor for nuclear power chain of China

International Nuclear Information System (INIS)

Ma Zhonghai; Pan Ziqiang; Xie Jianlun; Xiu Binglin

2001-01-01

The Greenhouse Gases Emission Factor (GGEF) for nuclear power chain of China is calculated based on Life Cycle Analysis method and the definition of full energy chain. There is no greenhouse gases released directly from nuclear power plant. The greenhouse gases emission from nuclear power plant is mainly from coal-fired electricity supply to nuclear power plant for its normal operation and the production of construction materials those are used in the nuclear power plant. The total GGEF of nuclear power chain in China is 13.71 g-co 2 /kWh. It is necessary to regulate un-rational power source mix and to use the energy sources in rational way for reducing the greenhouse gas effect. Nuclear power for electricity generation is one of effective ways to reduce greenhouse gases emission and retard the greenhouse effect

Confirmation of linear system theory prediction: Rate of change of Herrnstein's kappa as a function of response-force requirement.

Science.gov (United States)

McDowell, J J; Wood, H M

1985-01-01

Four human subjects worked on all combinations of five variable-interval schedules and five reinforcer magnitudes ( cent/reinforcer) in each of two phases of the experiment. In one phase the force requirement on the operandum was low (1 or 11 N) and in the other it was high (25 or 146 N). Estimates of Herrnstein's kappa were obtained at each reinforcer magnitude. The results were: (1) response rate was more sensitive to changes in reinforcement rate at the high than at the low force requirement, (2) kappa increased from the beginning to the end of the magnitude range for all subjects at both force requirements, (3) the reciprocal of kappa was a linear function of the reciprocal of reinforcer magnitude for seven of the eight data sets, and (4) the rate of change of kappa was greater at the high than at the low force requirement by an order of magnitude or more. The second and third findings confirm predictions made by linear system theory, and replicate the results of an earlier experiment (McDowell & Wood, 1984). The fourth finding confirms a further prediction of the theory and supports the theory's interpretation of conflicting data on the constancy of Herrnstein's kappa.

Low Frequency Electrostatic Waves in Weakly Inhomogeneous Magnetoplasma Modeled by Lorentzian (kappa) Distributions