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Sample records for carbon particles down-regulate

  1. Ultrafine carbon particles down-regulate CYP1B1 expression in human monocytes

    Directory of Open Access Journals (Sweden)

    Ziegler-Heitbrock Loems

    2009-10-01

    Full Text Available Abstract Background Cytochrome P450 monoxygenases play an important role in the defence against inhaled toxic compounds and in metabolizing a wide range of xenobiotics and environmental contaminants. In ambient aerosol the ultrafine particle fraction which penetrates deeply into the lungs is considered to be a major factor for adverse health effects. The cells mainly affected by inhaled particles are lung epithelial cells and cells of the monocyte/macrophage lineage. Results In this study we have analyzed the effect of a mixture of fine TiO2 and ultrafine carbon black Printex 90 particles (P90 on the expression of cytochrome P450 1B1 (CYP1B1 in human monocytes, macrophages, bronchial epithelial cells and epithelial cell lines. CYP1B1 expression is strongly down-regulated by P90 in monocytes with a maximum after P90 treatment for 3 h while fine and ultrafine TiO2 had no effect. CYP1B1 was down-regulated up to 130-fold and in addition CYP1A1 mRNA was decreased 13-fold. In vitro generated monocyte-derived macrophages (MDM, epithelial cell lines, and primary bronchial epithelial cells also showed reduced CYP1B1 mRNA levels. Benzo[a]pyrene (BaP is inducing CYB1B1 but ultrafine P90 can still down-regulate gene expression at 0.1 μM of BaP. The P90-induced reduction of CYP1B1 was also demonstrated at the protein level using Western blot analysis. Conclusion These data suggest that the P90-induced reduction of CYP gene expression may interfere with the activation and/or detoxification capabilities of inhaled toxic compounds.

  2. Down-regulation of small rubber particle protein expression affects integrity of rubber particles and rubber content in Taraxacum brevicorniculatum.

    Directory of Open Access Journals (Sweden)

    Andrea Hillebrand

    Full Text Available The biosynthesis of rubber is thought to take place on the surface of rubber particles in laticifers, highly specialized cells that are present in more than 40 plant families. The small rubber particle protein (SRPP has been supposed to be involved in rubber biosynthesis, and recently five SRPPs (TbSRPP1-5 were identified in the rubber-producing dandelion species Taraxacum brevicorniculatum. Here, we demonstrate by immunogold labeling that TbSRPPs are localized to rubber particles, and that rubber particles mainly consist of TbSRPP3, 4 and 5 as shown by high-resolution two-dimensional gel electrophoresis and mass spectrometric analysis. We also carried out an RNA-interference approach in transgenic plants to address the function of TbSRPPs in rubber biosynthesis as well as rubber particle morphology and stability. TbSRPP-RNAi transgenic T. brevicorniculatum plants showed a 40-50% reduction in the dry rubber content, but neither the rubber weight average molecular mass nor the polydispersity of the rubber were affected. Although no phenotypical differences to wild-type particles could be observed in vivo, rubber particles from the TbSRPP-RNAi transgenic lines were less stable and tend to rapidly aggregate in expelling latex after wounding of laticifers. Our results prove that TbSRPPs are very crucial for rubber production in T. brevicorniculatum, probably by contributing to a most favourable and stable rubber particle architecture for efficient rubber biosynthesis and eventually storage.

  3. Diurnal dynamics of oxygen and carbon dioxide concentrations in shoots and rhizomes of a perennial in a constructed wetland indicate down-regulation of below ground oxygen consumption

    Science.gov (United States)

    Faußer, Anna C.; Dušek, Jiří; Čížková, Hana; Kazda, Marian

    2016-01-01

    Wetland plants actively provide oxygen for aerobic processes in submerged tissues and the rhizosphere. The novel concomitant assessment of diurnal dynamics of oxygen and carbon dioxide concentrations under field conditions tests the whole-system interactions in plant-internal gas exchange and regulation. Oxygen concentrations ([O2]) were monitored in-situ in central culm and rhizome pith cavities of common reed (Phragmites australis) using optical oxygen sensors. The corresponding carbon dioxide concentrations ([CO2]) were assessed via gas samples from the culms. Highly dynamic diurnal courses of [O2] were recorded, which started at 6.5–13 % in the morning, increased rapidly up to 22 % during midday and declined exponentially during the night. Internal [CO2] were high in the morning (1.55–17.5 %) and decreased (0.04–0.94 %) during the rapid increase of [O2] in the culms. The observed negative correlations between [O2] and [CO2] particularly describe the below ground relationship between plant-mediated oxygen supply and oxygen use by respiration and biogeochemical processes in the rhizosphere. Furthermore, the nocturnal declining slopes of [O2] in culms and rhizomes indicated a down-regulation of the demand for oxygen in the complete below ground plant-associated system. These findings emphasize the need for measurements of plant-internal gas exchange processes under field conditions because it considers the complex interactions in the oxic-anoxic interface. PMID:27207278

  4. Can fast-growing plantation trees escape biochemical down-regulation of photosynthesis when grown throughout their complete production cycle in the open air under elevated carbon dioxide?

    Science.gov (United States)

    Davey, P A; Olcer, H; Zakhleniuk, O; Bernacchi, C J; Calfapietra, C; Long, S P; Raines, C A

    2006-07-01

    Poplar trees sustain close to the predicted increase in leaf photosynthesis when grown under long-term elevated CO2 concentration ([CO2]). To investigate the mechanisms underlying this response, carbohydrate accumulation and protein expression were determined over four seasons of growth. No increase in the levels of soluble carbohydrates was observed in the young expanding or mature sun leaves of the three poplar genotypes during this period. However, substantial increases in starch levels were observed in the mature leaves of all three poplar genotypes grown in elevated [CO2]. Despite the very high starch levels, no changes in the expression of photosynthetic Calvin cycle proteins, or in the starch biosynthetic enzyme ADP-glucose pyrophosphorylase (AGPase), were observed. This suggested that no long-term photosynthetic acclimation to CO2 occurred in these plants. Our data indicate that poplar trees are able to 'escape' from long-term, acclimatory down-regulation of photosynthesis through a high capacity for starch synthesis and carbon export. These findings show that these poplar genotypes are well suited to the elevated [CO2] conditions forecast for the middle of this century and may be particularly suited for planting for the long-term carbon sequestration into wood. PMID:17080946

  5. Diurnal dynamics of oxygen and carbon dioxide concentrations in shoots and rhizomes of a perennial in a constructed wetland indicate down-regulation of below ground oxygen consumption.

    Science.gov (United States)

    Faußer, Anna C; Dušek, Jiří; Čížková, Hana; Kazda, Marian

    2016-01-01

    Wetland plants actively provide oxygen for aerobic processes in submerged tissues and the rhizosphere. The novel concomitant assessment of diurnal dynamics of oxygen and carbon dioxide concentrations under field conditions tests the whole-system interactions in plant-internal gas exchange and regulation. Oxygen concentrations ([O2]) were monitored in-situ in central culm and rhizome pith cavities of common reed (Phragmites australis) using optical oxygen sensors. The corresponding carbon dioxide concentrations ([CO2]) were assessed via gas samples from the culms. Highly dynamic diurnal courses of [O2] were recorded, which started at 6.5-13 % in the morning, increased rapidly up to 22 % during midday and declined exponentially during the night. Internal [CO2] were high in the morning (1.55-17.5 %) and decreased (0.04-0.94 %) during the rapid increase of [O2] in the culms. The observed negative correlations between [O2] and [CO2] particularly describe the below ground relationship between plant-mediated oxygen supply and oxygen use by respiration and biogeochemical processes in the rhizosphere. Furthermore, the nocturnal declining slopes of [O2] in culms and rhizomes indicated a down-regulation of the demand for oxygen in the complete below ground plant-associated system. These findings emphasize the need for measurements of plant-internal gas exchange processes under field conditions because it considers the complex interactions in the oxic-anoxic interface. PMID:27207278

  6. Down-Regulation of KORRIGAN-Like Endo-β-1,4-Glucanase Genes Impacts Carbon Partitioning, Mycorrhizal Colonization and Biomass Production in Populus

    Science.gov (United States)

    Kalluri, Udaya C.; Payyavula, Raja S.; Labbé, Jessy L.; Engle, Nancy; Bali, Garima; Jawdy, Sara S.; Sykes, Robert W.; Davis, Mark; Ragauskas, Arthur; Tuskan, Gerald A.; Tschaplinski, Timothy J.

    2016-01-01

    A greater understanding of the genetic regulation of plant cell wall remodeling and the impact of modified cell walls on plant performance is important for the development of sustainable biofuel crops. Here, we studied the impact of down-regulating KORRIGAN-like cell wall biosynthesis genes, belonging to the endo-β-1,4-glucanase gene family, on Populus growth, metabolism and the ability to interact with symbiotic microbes. The reductions in cellulose content and lignin syringyl-to-guaiacyl unit ratio, and increase in cellulose crystallinity of cell walls of PdKOR RNAi plants corroborated the functional role of PdKOR in cell wall biosynthesis. Altered metabolism and reduced growth characteristics of RNAi plants revealed new implications on carbon allocation and partitioning. The distinctive metabolome phenotype comprised of a higher phenolic and salicylic acid content, and reduced lignin, shikimic acid and maleic acid content relative to control. Plant sustainability implications of modified cell walls on beneficial plant-microbe interactions were explored via co-culture with an ectomycorrhizal fungus, Laccaria bicolor. A significant increase in the mycorrhization rate was observed in transgenic plants, leading to measurable beneficial growth effects. These findings present new evidence for functional interconnectedness of cellulose biosynthesis pathway, metabolism and mycorrhizal association in plants, and further emphasize the consideration of the sustainability implications of plant trait improvement efforts. PMID:27757116

  7. Suppression of c-Myc is involved in multi-walled carbon nanotubes' down-regulation of ATP-binding cassette transporters in human colon adenocarcinoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Zhaojing [Department of Pharmacology, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, 430030 Wuhan (China); Xu, Yonghong [Institute of Ophthalmological Research, Department of Ophthalmology, Renmin Hospital of Wuhan University, 430060 Wuhan (China); Meng, Xiangning [School of Materials and Metallurgy, Northeastern University, Shenyang 110819 (China); Watari, Fumio [Department of Biomedical, Dental Materials and Engineering, Graduate School of Dental Medicine, Hokkaido University, Sapporo 060-8586 (Japan); Liu, Hudan, E-mail: hudanliu@hust.edu.cn [Department of Pharmacology, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, 430030 Wuhan (China); Chen, Xiao, E-mail: mornsmile@yahoo.com [Department of Pharmacology, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, 430030 Wuhan (China)

    2015-01-01

    Over-expression of ATP-binding cassette (ABC) transporters, a large family of integral membrane proteins that decrease cellular drug uptake and accumulation by active extrusion, is one of the major causes of cancer multi-drug resistance (MDR) that frequently leads to failure of chemotherapy. Carbon nanotubes (CNTs)-based drug delivery devices hold great promise in enhancing the efficacy of cancer chemotherapy. However, CNTs' effects on the ABC transporters remain under-investigated. In this study, we found that multiwalled carbon nanotubes (MWCNTs) reduced transport activity and expression of ABC transporters including ABCB1/Pgp and ABCC4/MRP4 in human colon adenocarcinoma Caco-2 cells. Proto-oncogene c-Myc, which directly regulates ABC gene expression, was concurrently decreased in MWCNT-treated cells and forced over-expression of c-Myc reversed MWCNTs' inhibitory effects on ABCB1 and ABCC4 expression. MWCNT-cell membrane interaction and cell membrane oxidative damage were observed. However, antioxidants such as vitamin C, β-mecaptoethanol and dimethylthiourea failed to antagonize MWCNTs' down-regulation of ABC transporters. These data suggest that MWCNTs may act on c-Myc, but not through oxidative stress, to down-regulate ABC transporter expression. Our findings thus shed light on CNTs' novel cellular effects that may be utilized to develop CNTs-based drug delivery devices to overcome ABC transporter-mediated cancer chemoresistance.

  8. Suppression of c-Myc is involved in multi-walled carbon nanotubes' down-regulation of ATP-binding cassette transporters in human colon adenocarcinoma cells

    International Nuclear Information System (INIS)

    Over-expression of ATP-binding cassette (ABC) transporters, a large family of integral membrane proteins that decrease cellular drug uptake and accumulation by active extrusion, is one of the major causes of cancer multi-drug resistance (MDR) that frequently leads to failure of chemotherapy. Carbon nanotubes (CNTs)-based drug delivery devices hold great promise in enhancing the efficacy of cancer chemotherapy. However, CNTs' effects on the ABC transporters remain under-investigated. In this study, we found that multiwalled carbon nanotubes (MWCNTs) reduced transport activity and expression of ABC transporters including ABCB1/Pgp and ABCC4/MRP4 in human colon adenocarcinoma Caco-2 cells. Proto-oncogene c-Myc, which directly regulates ABC gene expression, was concurrently decreased in MWCNT-treated cells and forced over-expression of c-Myc reversed MWCNTs' inhibitory effects on ABCB1 and ABCC4 expression. MWCNT-cell membrane interaction and cell membrane oxidative damage were observed. However, antioxidants such as vitamin C, β-mecaptoethanol and dimethylthiourea failed to antagonize MWCNTs' down-regulation of ABC transporters. These data suggest that MWCNTs may act on c-Myc, but not through oxidative stress, to down-regulate ABC transporter expression. Our findings thus shed light on CNTs' novel cellular effects that may be utilized to develop CNTs-based drug delivery devices to overcome ABC transporter-mediated cancer chemoresistance

  9. Human cytomegalovirus-encoded miR-US4-1 promotes cell apoptosis and benefits discharge of infectious virus particles via down-regulation of glutaminyl-tRNA synthetase, QARS in HCMV-infected HELF cells

    Indian Academy of Sciences (India)

    Yaozhong Shao; Ying Qi; Yujing Huang; Zhongyang Liu; Yanping Ma; Xin Guo; Shujuan Jiang; Zhengrong Sun; Qiang Ruan

    2016-06-01

    Human cytomegalovirus (HCMV) can cause congenital diseases and opportunistic infections in immunocompromised individuals. Its functional proteins and microRNAs (miRNAs) facilitate efficient viral propagation by altering host cell behaviour. Identification of functional target genes of miRNAs is an important step in studies on HCMV pathogenesis. In this study, Glutaminyl-tRNA Synthetase (QARS), which could regulate signal transduction pathways for cellular apoptosis, was identified as a direct target of hcmv-miR-US4-1. Apoptosis assay revealed that as silence of QARS by ectopic expression of hcmv-miR-US4-1 and specific small interference RNA of QARS can promote cell apoptosis in HCMV-infected HELF cells. Moreover, viral growth curve assays showed that hcmv-miR-US4-1 benefits the discharge of infectious virus particles. However, silence of hcmv-miR-US4-1 by its specific inhibitor overturned these effects. These results imply that hcmv-miR-US4-1 might have the same effects during HCMV nature infection. In general, hcmv-miR-US4-1 may involve in promoting cell apoptosis and benefiting discharge of infectious virus particles via down-regulation of QARS in HCMV-infected HELF cells.

  10. The effect of down-regulation of Smad3 by RNAi on hepatic stellate cells and a carbon tetrachloride-induced rat model of hepatic fibrosis

    Directory of Open Access Journals (Sweden)

    Z.R. Wang

    2011-02-01

    Full Text Available Searching for effective Smad3 gene-based gene therapies for hepatic fibrosis, we constructed siRNA expression plasmids targeting the rat Smad3 gene and then delivered these plasmids into hepatic stellate cells (HSCs. The effect of siRNAs on the mRNA levels of Smad2, Smad3, Smad4, and collagens I-α1, III-α1 and IV-α1 (Colα1, Col3α1, Col4α1, respectively was determined by RT-PCR. Eighty adult male Sprague-Dawley rats were randomly divided into three groups. Twice a week for 8 weeks, the untreated hepatic fibrosis model (N = 30 and the treated group (N = 20 were injected subcutaneously with 40% (v/v carbon tetrachloride (CCl4-olive oil (3 mL/kg, and the normal control group (N = 30 was injected with olive oil (3 mL/kg. In the 4th week, the treated rats were injected subcutaneously with liposome-encapsulated plasmids (150 µg/kg into the right liver lobe under general anesthesia once every 2 weeks, and the untreated rats were injected with the same volume of buffer. At the end of the 6th and 8th weeks, liver tissue and sera were collected. Pathological changes were assessed by a semi-quantitative scoring system (SSS, and a radioimmunoassay was used to establish a serum liver fibrosis index (type III procollagen, type IV collagen, laminin, and hyaluronic acid. The mRNA expression levels of the above cited genes were reduced in the HSCs transfected with the siRNA expression plasmids. Moreover, in the treated group, fibrosis evaluated by the SSS was significantly reduced (P < 0.05 and the serum indices were greatly improved (P < 0.01. These results suggest that Smad3 siRNA expression plasmids have an anti-fibrotic effect.

  11. Carbon fuel particles used in direct carbon conversion fuel cells

    Science.gov (United States)

    Cooper, John F.; Cherepy, Nerine

    2012-10-09

    A system for preparing particulate carbon fuel and using the particulate carbon fuel in a fuel cell. Carbon particles are finely divided. The finely dividing carbon particles are introduced into the fuel cell. A gas containing oxygen is introduced into the fuel cell. The finely divided carbon particles are exposed to carbonate salts, or to molten NaOH or KOH or LiOH or mixtures of NaOH or KOH or LiOH, or to mixed hydroxides, or to alkali and alkaline earth nitrates.

  12. Role of the Endosomal ESCRT Machinery in HIV-1 Vpu-Induced Down-Regulation of BST2/Tetherin. : HRS and BST-2/Tetherin Down-Regulation

    OpenAIRE

    Janvier, Katy; Pelchen-Matthews, Annegret; Jean-Baptiste, Renaud; Caillet, Marina; Marsh, Mark; Berlioz-Torrent, Clarisse

    2012-01-01

    International audience The cellular protein "Bone marrow stromal antigen 2" (BST2 also called Tetherin, CD317, HM1.24) was identified as a major mediator of the innate immune defense against the dissemination of enveloped viruses. BST2 was shown to physically trap the de novo formed viral particles at the surface of infected cells, thereby reducing viral release. Lentiviruses have evolved specific strategies to down-regulate the expression level of BST2 from the surface of the cells and as...

  13. Photosynthesis down-regulation precedes carbohydrate accumulation under sink limitation in Citrus.

    Science.gov (United States)

    Nebauer, Sergio G; Renau-Morata, Begoña; Guardiola, José Luis; Molina, Rosa-Victoria

    2011-02-01

    Photosynthesis down-regulation due to an imbalance between sources and sinks in Citrus leaves could be mediated by excessive accumulation of carbohydrates. However, there is limited understanding of the physiological role of soluble and insoluble carbohydrates in photosynthesis regulation and the elements triggering the down-regulation process. In this work, the role of non-structural carbohydrates in the regulation of photosynthesis under a broad spectrum of source-sink relationships has been investigated in the Salustiana sweet orange. Soluble sugar and starch accumulation in leaves, induced by girdling experiments, did not induce down-regulation of the photosynthetic rate in the presence of sinks (fruits). The leaf-to-fruit ratio did not modulate photosynthesis but allocation of photoassimilates to the fruits. The lack of strong sink activity led to a decrease in the photosynthetic rate and starch accumulation in leaves. However, photosynthesis down-regulation due to an excess of total soluble sugars or starch was discarded because photosynthesis and stomatal conductance reduction occurred prior to any significant accumulation of these carbohydrates. Gas exchange and fluorescence parameters suggested biochemical limitations to photosynthesis. In addition, the expression of carbon metabolism-related genes was altered within 24 h when strong sinks were removed. Sucrose synthesis and export genes were inhibited, whereas the expression of ADP-glucose pyrophosphorylase was increased to cope with the excess of assimilates. In conclusion, changes in starch and soluble sugar turnover, but not sugar content per se, could provide the signal for photosynthesis regulation. In these conditions, non-stomatal limitations strongly inhibited the photosynthetic rate prior to any significant increase in carbohydrate levels. PMID:21367744

  14. Carbon-rich particles in Comet Halley

    International Nuclear Information System (INIS)

    The majority of particles detected in the coma of Comet Halley contain carbon atoms; many of these grains appear to consist preponderately or only of light elements. These light-element particles may be composed of organic compounds. Of the possible combinations of the elements hydrogen, carbon, nitrogen, and oxygen, numerous examples are found of particles containing the combinations (H,C,O,N), (H,C,N), (H,C,O), and (H,C). These results may bear on the recent detection of polyoxymethylene fragments, the observation of cyanojets (CN patterns consistent with release from solid particles), the possible presence of cyanopolyacetylenes or HCN polymer and the make-up of the CHON particles. If cometary matter could reach the surface of the earth without complete disruption, these diverse organic and mixed particles could create unique microenvironments, possibly with significant or even pivotal prebiotic chemical activity. Here a speculative insight into possible relationships between carbon in comets and carbon in life is given, as well as a brief overview of on-going analysis of data from the highly successful Particle Impact Analyzer (PIA) experiment flown on the Giotto spacecraft for the flyby of Comet Halley (development and implementation of PIA was under the direction of J. Kissel of the Max Planck Institute for Kernphysik, Heidelberg). PIA is a time-of-flight analyzer which obtains mass spectra of ions from individual particles impacting on a Pt-Ag foil target within the instrument

  15. DMBT1 expression is down-regulated in breast cancer

    DEFF Research Database (Denmark)

    Braidotti, P; Nuciforo, P G; Mollenhauer, J;

    2004-01-01

    BACKGROUND: We studied the expression of DMBT1 (deleted in malignant brain tumor 1), a putative tumor suppressor gene, in normal, proliferative, and malignant breast epithelium and its possible relation to cell cycle. METHODS: Sections from 17 benign lesions and 55 carcinomas were immunostained...... and hyperplastic mammary cells positive with DMBTh12 were also MCM5-positive. CONCLUSIONS: The redistribution and up-regulation of DMBT1 in normal and hyperplastic tissues flanking malignant tumours and its down-regulation in carcinomas suggests a potential role in breast cancer. Moreover, the concomitant...

  16. Protection of porous carbon fuel particles from boudouard corrosion

    Energy Technology Data Exchange (ETDEWEB)

    Cooper, John F.

    2015-05-26

    A system for producing energy that includes infusing porous carbon particles produced by pyrolysis of carbon-containing materials with an off-eutectic salt composition thus producing pore-free carbon particles, and reacting the carbon particles with oxygen in a fuel cell according to the reaction C+O.sub.2=CO.sub.2 to produce electrical energy.

  17. Synthesis of carbon nanofibers on copper particles

    Science.gov (United States)

    Kol'tsova, T. S.; Larionova, T. V.; Shusharina, N. N.; Tolochko, O. V.

    2015-08-01

    We analyze the synthesis of carbon nanostructures from the gas phase (mixture of acetylene or ethylene with hydrogen) on the surface of copper particles without using other catalysts. The synthesized structures (multilayer graphene and carbon nanofibers) are analyzed by transmission electron microscopy and Raman scattering. It is shown that the fiber structure is determined by the C: H ratio in the gas phase. The kinetics of synthesis is analyzed in terms of the formal kinetics of conversion in accordance with the Johnson—Mehl—Avrami equation.

  18. Carbon-Supported Iron Oxide Particles

    DEFF Research Database (Denmark)

    Meaz, T.; Mørup, Steen; Koch, C. Bender

    1996-01-01

    A carbon black ws impregnated with 6 wt% iron using an aqueous solution of iron nitrate. The impregnated carbon was initially dried at 125 C. The effect of heating of the iron oxide phase was investigated at temperatures between 200 and 600 C using Mossbauer spectroscopy. All heat treatments were...... done in an oxygen-containing atmosphere. Ferrihydrite is formed and is stable at and below a temperature of 300 C. At 600 C small particles of maghemite is the dominant iron oxide. A transformation reaction is suggested....

  19. Tryptanthrin ameliorates atopic dermatitis through down-regulation of TSLP.

    Science.gov (United States)

    Han, Na-Ra; Moon, Phil-Dong; Kim, Hyung-Min; Jeong, Hyun-Ja

    2014-01-15

    Atopic dermatitis (AD) is a common skin disease that greatly worsens quality of life. Thymic stromal lymphopoietin (TSLP) plays a decisive role in the development of AD. The purpose of this study is to examine whether tryptanthrin (TR) would suppress AD through the regulation of TSLP. We analyzed the effect of TR on the level of TSLP from phorbol myristate acetate/calcium ionophore A23187-activated human mast cell line, HMC-1 cells, in 2,4-dinitrofluorobenzene-induced AD-like skin lesions of NC/Nga mice, and in anti-CD3/anti-CD28-stimulated splenocytes. TR significantly suppressed the level of intracellular calcium and the production and mRNA expression of TSLP through the blockade of receptor-interacting protein 2/caspase-1/nuclear factor-κB pathway in the activated HMC-1 cells. TR also significantly suppressed the levels of histidine decarboxylase and IL-1β. Furthermore, TR ameliorated clinical symptoms in the AD model. TR significantly reduced the levels of TSLP, IL-4, IFN-γ, IL-6, TNF-α, thymus and activation-regulated chemokine, and caspase-1 in AD skin lesions. Also, TR significantly reduced the serum levels of histamine and IL-4 in the AD model. Finally, TR significantly inhibited the production of IL-4, IFN-γ, and TNF-α from the stimulated splenocytes. Taken together, TR exhibits the potential to be a therapeutic agent for AD through down-regulation of TSLP. PMID:24295961

  20. Particle trapping using dielectrophoretically patterned carbon nanotubes.

    Science.gov (United States)

    Khoshmanesh, Khashayar; Zhang, Chen; Nahavandi, Saeid; Tovar-Lopez, Francisco J; Baratchi, Sara; Hu, Zheng; Mitchell, Arnan; Kalantar-Zadeh, Kourosh

    2010-04-01

    This study presents the dielectrophoretic (DEP) assembly of multi-walled carbon nanotubes (MWCNTs) between curved microelectrodes for the purpose of trapping polystyrene microparticles within a microfluidic system. Under normal conditions, polystyrene particles exhibit negative DEP behaviour and are repelled from microelectrodes. Interestingly, the addition of MWCNTs to the system alters this situation in two ways: first, they coat the surface of particles and change their dielectric properties to exhibit positive DEP behaviour; second, the assembled MWCNTs are highly conductive and after the deposition serve as extensions to the microelectrodes. They establish an array of nanoelectrodes that initiates from the edge of microelectrodes and grow along the electric field lines. These nanoelectrodes can effectively trap the MWCNT-coated particles, since they cover a large portion of the microchannel bottom surface and also create a much stronger electric field than the primary microelectrodes as confirmed by our numerical simulations. We will show that the presence of MWCNT significantly changes performance of the system, which is investigated by trapping sample polystyrene particles with plain, COOH and goat anti-mouse IgG surfaces. PMID:20301125

  1. CCN activation of pure and coated carbon black particles.

    Science.gov (United States)

    Dusek, U; Reischl, G P; Hitzenberger, R

    2006-02-15

    The CCN (cloud condensation nucleus) activation of pure and coated carbon black particles was investigated using the University of Vienna cloud condensation nuclei counter (Giebl, H.; Berner, A.; Reischl, G.; Puxbaum, H.; Kasper-Giebl, A.; Hitzenberger, R. J. Aerosol Sci. 2002, 33, 1623-1634). The particles were produced by nebulizing an aqueous suspension of carbon black in a Collison atomizer. The activation of pure carbon black particles was found to require higher supersaturations than predicted by calculations representing the particles as insoluble, wettable spheres with mobility equivalent diameter. To test whether this effect is an artifact due to heating of the light-absorbing carbon black particles in the laser beam, experiments at different laser powers were conducted. No systematic dependence of the activation of pure carbon black particles on laser power was observed. The observations could be modeled using spherical particles and an effective contact angle of 4-6 degrees of water at their surface. The addition of a small amount of NaCl to the carbon black particles (by adding 5% by mass NaCl to the carbon black suspension) greatly enhanced their CCN efficiency. The measured CCN efficiencies were consistent with Kohler theory for particles consisting of insoluble and hygroscopic material. However, coating the carbon black particles with hexadecanol (a typical film-forming compound with one hydrophobic and one hydrophilic end) efficiently suppressed the CCN activation of the carbon black particles.

  2. Two distinct pathways exist for down-regulation of the TCR

    DEFF Research Database (Denmark)

    Lauritsen, J P; Christensen, M D; Dietrich, J;

    1998-01-01

    -induced TCR down-regulation is mediated by two distinct, independent mechanisms. Ligand-induced TCR down-regulation is dependent on the protein tyrosine kinases p56(lck) and p59(fyn) but independent of PKC and the CD3gamma leucine-based (L-based) internalization motif. In contrast, PKC-induced TCR down-regulation......TCR down-regulation plays an important role in modulating T cell responses both during T cell development and in mature T cells. Down-regulation of the TCR is induced by engagement of the TCR by specific ligands and/or by activation of protein kinase C (PKC). We report here that ligand- and PKC...

  3. Down-regulation of CTLA-4 by HIV-1 Nef protein.

    OpenAIRE

    Mohamed El-Far; Catherine Isabelle; Nicolas Chomont; Martin Bourbonnière; Simone Fonseca; Petronela Ancuta; Yoav Peretz; Younes Chouikh; Rabih Halwani; Olivier Schwartz; Joaquín Madrenas; Freeman, Gordon J.; Jean-Pierre Routy; Haddad, Elias K.; Rafick-Pierre Sékaly

    2013-01-01

    International audience HIV-1 Nef protein down-regulates several cell surface receptors through its interference with the cell sorting and trafficking machinery. Here we demonstrate for the first time the ability of Nef to down-regulate cell surface expression of the negative immune modulator CTLA-4. Down-regulation of CTLA-4 required the Nef motifs DD175, EE155 and LL165, all known to be involved in vesicle trafficking. Disruption of the lysosomal functions by pH-neutralizing agents preven...

  4. Blackbody Radiation and the Carbon Particle

    Directory of Open Access Journals (Sweden)

    Pierre-Marie Robitaille

    2008-07-01

    Full Text Available Since the days of Kirchhoff, blackbody radiation has been considered to be a universal process, independent of the nature and shape of the emitter. Nonetheless, in promoting this concept, Kirchhoff did require, at the minimum, thermal equilibrium with an enclosure. Recently, the author stated (P.-M. Robitaille, IEEE Trans. Plasma Sci., 2003, v.31(6, 1263-1267; P.-M. Robitaille, Progr. in Phys., 2006, v.2, 22-23, that blackbody radiation is not universal and has called for a return to Stewart's law (P.-M. Robitaille, Progr. in Phys., 2008, v.3, 30-35. In this work, a historical analysis of thermal radiation is presented. It is demonstrated that soot, or lampblack, was the standard for blackbody experiments throughout the 1800s. Furthermore, graphite and carbon black continue to play a central role in the construction of blackbody cavities. The advent of universality is reviewed through the writings of Pierre Prevost, Pierre Louis Dulong, Alexis Therese Petit, Jean Baptiste Joseph Fourier, Simeon Denis Poisson, Frederick Herve de la Provostaye, Paul Quentin Desain, Balfour Stewart, Gustav Robert Kirchhoff, and Max Karl Ernst Ludwig Planck. These writings illustrate that blackbody radiation, as experimentally produced in cavities and as discussed theoretically, has remained dependent on thermal equilibrium with at least the smallest carbon particle. Finally, Planck's treatment of Kirchhoff's law is examined in detail and the shortcomings of his derivation are outlined. It is shown once again, that universality does not exist. Only Stewart's law of thermal emission, not Kirchhoff's, is fully valid.

  5. The Mycobacterium tuberculosis H37Ra gene MRA_1916 causes growth defects upon down-regulation.

    Science.gov (United States)

    Singh, Kumar Sachin; Singh, Sudheer Kumar

    2015-01-01

    D-amino acid oxidases play an important role in converting D-amino acids to their corresponding α-keto acids. MRA_1916 of Mycobacterium tuberculosis H37Ra (Mtb-Ra) is annotated to be a D-amino acid oxidase (DAO). However, not much information is available about its physiological role during Mtb-Ra growth and survival. The present study was taken-up to understand the role of DAO during different stages of growth and effect of its down-regulation on growth. Recombinant Mtb-Ra strains with DAO and GlcB (malate synthase: MRA_1848) gene knockdown were developed and their growth was studied using Microtiter Alamar Blue Assay (MABA) with glycerol, acetate and glycine as a carbon source. Ethyl bromopyruvate (BrP) was used as an inhibitor of GlcB. MABA study showed inhibition of wild-type (WT) and knockdowns in the presence of BrP (2.5mM). However, growth inhibition of WT was less noticeable at lower concentrations of BrP. Mtb-Ra with DAO knockdown showed poor utilization of glycine in the presence of BrP. The DAO localization study showed its prominent distribution in cytosolic fraction and to some extent in cell wall and membrane fractions. Growth profile of WT under oxygen and nutritional stress showed changes in expression of DAO, GlcB, PckA (phosphoenolpyruvate carboxykinase: MRA_0219) and GlyA1 (serine hydroxymethyltransferase: MRA_1104). PMID:26531045

  6. Lygodium flexuosum extract down regulates the expression of proinflammatory cytokines in CCl4 -induced hepatotoxicity

    Institute of Scientific and Technical Information of China (English)

    Pallara Janardhanan Wills; Velikkakathu Vasumathi Asha

    2012-01-01

    Objective:To examine the downregulation of proinflammatory cytokines in a time dependant manner on carbon tetrachloride induced toxicity in experimental animals.Methods:CCl4(150 μL/100 g) was dissolved in corn oil(1:1 v/v%) and administered orally.GroupI was treated as normal control and received corn oil on8th day.GroupII was toxic control and was given a single dose ofCCl4 on8th days.GroupIII wastreated withLygodium flexuosum(L. flexuosum)n-hexane extract(200 mg/kg) for8 days and on8th day a single dose ofCCl4 was received.GroupIV(negative control) receivedL. flexuosumn-hexane extract(200 mg/kg) alone for8 days.Results:Treatment withn-hexane extract prior to the administration ofCCl4 significantly prevented an increase in serumAST,ALT,LDH activity and lipid peroxidation and prevented the depletion of glutathione (GSH).Rats treated withL. flexuosum had reduced mRNA levels ofTGF-β1,TNF-α andIL-1βgenes in liver ofCCl4 intoxicated rats when compared toCCl4 control as evidenced byRT-PCR. Conclusions:The data suggest that L. flexuosum, a widely available fern, significantly reduces CCl4 induced acute hepatotoxicity by down-regulating the expression of pro-inflammatory cytokines in rats.

  7. Par-4 Down-regulation Promotes Breast Cancer Recurrence by Preventing Multinucleation following Targeted Therapy

    OpenAIRE

    Alvarez, James V.; Pan, Tien-chi; Ruth, Jason; Feng, Yi; Zhou, Alice; Pant, Dhruv; Grimley, Joshua S.; Wandless, Thomas J.; DeMichele, Angela; Chodosh, Lewis A.

    2013-01-01

    Most deaths from breast cancer result from tumor recurrence, but the mechanisms underlying tumor relapse are largely unknown. We now report that Par-4 is down-regulated during tumor recurrence and that Par-4 down-regulation is necessary and sufficient to promote recurrence. Tumor cells with low Par-4 expression survive therapy by evading a program of Par-4-dependent multinucleation and apoptosis that is otherwise engaged following treatment. Low Par-4 expression is associated with poor respon...

  8. The Carboxyl Terminus of VEGFR-2 Is Required for PKC-mediated Down-Regulation

    OpenAIRE

    Singh, Amrik J.; Meyer, Rosana D.; Band, Hamid; Rahimi, Nader

    2005-01-01

    Vascular endothelial growth factor receptor-2 (VEGFR-2/Flk-1) is a receptor tyrosine kinase (RTK) whose activation regulates angiogenesis. The regulatory mechanisms that attenuate VEGFR-2 signal relay are largely unknown. Our study shows that VEGFR-2 promotes phosphorylation of c-Cbl, but activation, ubiquitylation, and down-regulation of VEGFR-2 are not influenced by c-Cbl activity. A structure-function analysis of VEGFR-2 and pharmacological approach revealed that down-regulation of VEGFR-2...

  9. Toughening of polypropylene with calcium carbonate particles

    NARCIS (Netherlands)

    Zuiderduin, W.C.J.; Westzaan, C.; Huetink, J.; Gaymans, R.J.

    2003-01-01

    Polypropylene–CaCO3 composites were prepared on a twin screw extruder with a particle content of 0–32 vol%. The influence of particle size (0.07–1.9 μm) and surface treatment of the particles (with and without stearic acid) on the toughening properties were studied. The matrix molecular weight of th

  10. Delta-Like Ligand 4 Modulates Liver Damage by Down-Regulating Chemokine Expression.

    Science.gov (United States)

    Shen, Zhe; Liu, Yan; Dewidar, Bedair; Hu, Junhao; Park, Ogyi; Feng, Teng; Xu, Chengfu; Yu, Chaohui; Li, Qi; Meyer, Christoph; Ilkavets, Iryna; Müller, Alexandra; Stump-Guthier, Carolin; Munker, Stefan; Liebe, Roman; Zimmer, Vincent; Lammert, Frank; Mertens, Peter R; Li, Hai; Ten Dijke, Peter; Augustin, Hellmut G; Li, Jun; Gao, Bin; Ebert, Matthias P; Dooley, Steven; Li, Youming; Weng, Hong-Lei

    2016-07-01

    Disrupting Notch signaling ameliorates experimental liver fibrosis. However, the role of individual Notch ligands in liver damage is unknown. We investigated the effects of Delta-like ligand 4 (Dll4) in liver disease. DLL4 expression was measured in 31 human liver tissues by immunohistochemistry. Dll4 function was examined in carbon tetrachloride- and bile duct ligation-challenged mouse models in vivo and evaluated in hepatic stellate cells, hepatocytes, and Kupffer cells in vitro. DLL4 was expressed in patients' Kupffer and liver sinusoidal endothelial cells. Recombinant Dll4 protein (rDll4) ameliorated hepatocyte apoptosis, inflammation, and fibrosis in mice after carbon tetrachloride challenge. In vitro, rDll4 significantly decreased lipopolysaccharide-dependent chemokine expression in both Kupffer and hepatic stellate cells. In bile duct ligation mice, rDll4 induced massive hepatic necrosis, resulting in the death of all animals within 1 week. Inflammatory cell infiltration and chemokine ligand 2 (Ccl2) expression were significantly reduced in rDll4-receiving bile duct ligation mice. Recombinant Ccl2 rescued bile duct ligation mice from rDll4-mediated death. In patients with acute-on-chronic liver failure, DLL4 expression was inversely associated with CCL2 abundance. Mechanistically, Dll4 regulated Ccl2 expression via NF-κB. Taken together, Dll4 modulates liver inflammatory response by down-regulating chemokine expression. rDll4 application results in opposing outcomes in two models of liver damage. Loss of DLL4 may be associated with CCL2-mediated cytokine storm in patients with acute-on-chronic liver failure. PMID:27171900

  11. Antibody-induced down-regulation of a mutated insulin receptor lacking an intact cytoplasmic domain

    International Nuclear Information System (INIS)

    Insulin receptor down-regulation was studied in various Chinese hamster ovary (CHO) cell lines expressing transfected human insulin receptor cDNAs. In addition to a cell line expressing the normal receptor (CHO.T line), three lines expressing mutated receptors were studied: the CHO.T-t line, which expresses a receptor with a degraded cytoplasmic domain due to the removal of the C-terminal 112 amino acids, and the CHO.YF1 and CHO.YF3 lines, in which important autophosphorylation sites of the receptor kinase (tyrosines-1162 and -1163) have been replaced by phenylalanine. A monoclonal anti-receptor antibody, but not insulin itself, was found to down-regulate cell surface receptor levels in all four cell lines by 60-80% after 18-h treatment at 370C. Down-regulation of the CHO.T and CHO.T-t receptors occurred at similar antibody concentrations and with a similar time course, although the maximum level of CHO.T-t down-regulation (60%) was generally lower than the level of CHO.T down-regulation (80%). Pulse-chase labeling of these two cell types with [35S]methionine revealed that antibody treatment of both CHO.T and CHO.T-t cells resulted in a similar increase in the rate of degradation of mature receptor subunits. These results indicate that antibody-induced down-regulation of the insulin receptor in these cells can occur in the absence of various autophosphorylation sites of the receptor and that the mechanism of antibody-induced down-regulation is different from that for insulin

  12. TCR down-regulation boosts T-cell-mediated cytotoxicity and protection against poxvirus infections

    DEFF Research Database (Denmark)

    Hansen, Ann K; Regner, Matthias; Bonefeld, Charlotte M;

    2011-01-01

    Cytotoxic T (Tc) cells play a key role in the defense against virus infections. Tc cells recognize infected cells via the T-cell receptor (TCR) and subsequently kill the target cells by one or more cytotoxic mechanisms. Induction of the cytotoxic mechanisms is finely tuned by the activation signals...... from the TCR. To determine whether TCR down-regulation affects the cytotoxicity of Tc cells, we studied TCR down-regulation-deficient CD3¿LLAA mice. We found that Tc cells from CD3¿LLAA mice have reduced cytotoxicity due to a specific deficiency in exocytosis of lytic granules. To determine whether....... Finally, we found that TCR signaling in CD3¿LLAA Tc cells caused highly increased tyrosine phosphorylation and activation of the c-Cbl ubiquitin ligase, and that the impaired exocytosis of lytic granules could be rescued by the knockdown of c-Cbl. Thus, our work demonstrates that TCR down-regulation...

  13. Down-regulation of microRNAs controlling tumourigenic factors in follicular thyroid carcinoma

    DEFF Research Database (Denmark)

    Rossing, Maria; Helweg-Larsen, Rehannah Borup; Henao Giraldo, Ricardo;

    2012-01-01

    ) and follicular carcinoma (FC). Comparison of carcinoma and adenoma with normal thyroid revealed 150 and 107 differentially expressed miRNAs. Most miRNAs were down-regulated and especially miR-199b-5p and miR-144 which were essentially lost in the carcinomas. Integration of the changed miRNAs with differentially......RNAs in FC exhibited a substantial similarity with down-regulated miRNAs in anaplastic carcinoma and by gene set enrichment analysis, we observed a significant identity between target mRNAs in FC and transcripts up-regulated in anaplastic carcinoma. To examine the diagnostic potential of miRNA expression...

  14. Worker exposure to ultrafine particles during carbon black treatment

    Directory of Open Access Journals (Sweden)

    Urszula Mikołajczyk

    2015-07-01

    Full Text Available Background: The aim of the project was to assess the exposure of workers to ultrafine particles released during handling and packing of carbon black. The assessment included the results of the measurements performed in a carbon black handling plant before, during, and after work shift. Material and Methods: The number concentration of particles within the dimension range 10–1000 nm and 10–100 nm was assayed by a condensation particle counter (CPC. The mass concentration of particles was determined by a DustTrak II DRX aerosol concentration monitor. The surface area concentration of the particles potentially deposited in the alveolar (A and tracheo-bronchial (TB regions was estimated by an AeroTrak 9000 nanoparticle monitor. Results: An average mass concentration of particles during the process was 6-fold higher than that before its start, while a 3-fold increase in the average number concentration of particles within the dimension range 10–1000 nm and 10–100 nm was observed during the process. At the same time a 4-fold increase was found in the surface area concentration of the particles potentially deposited in the A and TB regions. Conclusions: During the process of carbon black handling and packing a significantly higher values of each of the analysed parameters, characterizing the exposure to ultrafine particles, were noted. Med Pr 2015;66(3:317–326

  15. Synthesis of carbon nanotubes with and without catalyst particles

    Directory of Open Access Journals (Sweden)

    Cuniberti Gianaurelio

    2011-01-01

    Full Text Available Abstract The initial development of carbon nanotube synthesis revolved heavily around the use of 3d valence transition metals such as Fe, Ni, and Co. More recently, noble metals (e.g. Au and poor metals (e.g. In, Pb have been shown to also yield carbon nanotubes. In addition, various ceramics and semiconductors can serve as catalytic particles suitable for tube formation and in some cases hybrid metal/metal oxide systems are possible. All-carbon systems for carbon nanotube growth without any catalytic particles have also been demonstrated. These different growth systems are briefly examined in this article and serve to highlight the breadth of avenues available for carbon nanotube synthesis.

  16. Effect of a biological activated carbon filter on particle counts

    Institute of Scientific and Technical Information of China (English)

    Su-hua WU; Bing-zhi DONG; Tie-jun QIAO; Jin-song ZHANG

    2008-01-01

    Due to the importance of biological safety in drinking water quality and the disadvantages which exist in traditional methods of detecting typical microorganisms such as Cryptosporidium and Giardia,it is necessary to develop an alternative.Particle counts is a qualitative measurement of the amount of dissolved solids in water.The removal rate of particle counts was previously used as an indicator of the effectiveness of a biological activated carbon(BAC)filter in removing Cryptosporidium and Giardia.The particle counts in a BAC filter effluent over one operational period and the effects of BAC filter construction and operational parameters were investigated with a 10 m3/h pilot plant.The results indicated that the maximum particle count in backwash remnant water was as high as 1296 count/ml and it needed about 1.5 h to reduce from the maximum to less than 50 count/ml.During the standard filtration period,particle counts stay constant at less than 50 count/ml for 5 d except when influ-enced by sand filter backwash remnant water.The removal rates of particle counts in the BAC filter are related to characteristics of the carbon.For example,a columned carbon and a sand bed removed 33.3% and 8.5% of particles,respectively,while the particle counts in effluent from a cracked BAC filter was higher than that of the influent.There is no significant difference among particle removal rates with different filtration rates.High post-ozone dosage(>2 mg/L)plays an important role in particle count removal;when the dosage was 3 mg/L,the removal rates by carbon layers and sand beds decreased by 17.5% and increased by 9.5%,respectively,compared with a 2 mg/L dosage.

  17. A herbivorous mite down-regulates plant defence and produces web to exclude competitors.

    Science.gov (United States)

    Sarmento, Renato A; Lemos, Felipe; Dias, Cleide R; Kikuchi, Wagner T; Rodrigues, Jean C P; Pallini, Angelo; Sabelis, Maurice W; Janssen, Arne

    2011-01-01

    Herbivores may interact with each other through resource competition, but also through their impact on plant defence. We recently found that the spider mite Tetranychus evansi down-regulates plant defences in tomato plants, resulting in higher rates of oviposition and population growth on previously attacked than on unattacked leaves. The danger of such down-regulation is that attacked plants could become a more profitable resource for heterospecific competitors, such as the two-spotted spider mite Tetranychus urticae. Indeed, T. urticae had an almost 2-fold higher rate of oviposition on leaf discs on which T. evansi had fed previously. In contrast, induction of direct plant defences by T. urticae resulted in decreased oviposition by T. evansi. Hence, both herbivores affect each other through induced plant responses. However, when populations of T. evansi and T. urticae competed on the same plants, populations of the latter invariably went extinct, whereas T. evansi was not significantly affected by the presence of its competitor. This suggests that T. evansi can somehow prevent its competitor from benefiting from the down-regulated plant defence, perhaps by covering it with a profuse web. Indeed, we found that T. urticae had difficulties reaching the leaf surface to feed when the leaf was covered with web produced by T. evansi. Furthermore, T. evansi produced more web when exposed to damage or other cues associated with T. urticae. We suggest that the silken web produced by T. evansi serves to prevent competitors from profiting from down-regulated plant defences.

  18. Expression of NDRG2 is down-regulated in high-risk adenomas and colorectal carcinoma

    DEFF Research Database (Denmark)

    Lorentzen, Anders; Vogel, Lotte K.; Lewinsky, Rikke H;

    2007-01-01

    BACKGROUND: It has recently been shown that NDRG2 mRNA is down-regulated or undetectable in several human cancers and cancer cell-lines. Although the function of NDRG2 is unknown, high NDRG2 expression correlates with improved prognosis in high-grade gliomas. The aim of this study has been to exa...

  19. Rapid male-specific regulatory divergence and down regulation of spermatogenesis genes in Drosophila species hybrids.

    Directory of Open Access Journals (Sweden)

    Jennifer Ferguson

    Full Text Available In most crosses between closely related species of Drosophila, the male hybrids are sterile and show postmeiotic abnormalities. A series of gene expression studies using genomic approaches have found significant down regulation of postmeiotic spermatogenesis genes in sterile male hybrids. These results have led some to suggest a direct relationship between down regulation in gene expression and hybrid sterility. An alternative explanation to a cause-and-effect relationship between misregulation of gene expression and male sterility is rapid divergence of male sex regulatory elements leading to incompatible interactions in an interspecies hybrid genome. To test the effect of regulatory divergence in spermatogenesis gene expression, we isolated 35 fertile D. simulans strains with D. mauritiana introgressions in either the X, second or third chromosome. We analyzed gene expression in these fertile hybrid strains for a subset of spermatogenesis genes previously reported as significantly under expressed in sterile hybrids relative to D. simulans. We found that fertile autosomal introgressions can cause levels of gene down regulation similar to that of sterile hybrids. We also found that X chromosome heterospecific introgressions cause significantly less gene down regulation than autosomal introgressions. Our results provide evidence that rapid male sex gene regulatory divergence can explain misexpression of spermatogenesis genes in hybrids.

  20. Possible Power Estimation of Down-Regulated Offshore Wind Power Plants

    DEFF Research Database (Denmark)

    Gögmen, Tuhfe

    The penetration of offshore wind power is continuously increasing in the Northern European grids. To assure safety in the operation of the power system, wind power plants are required to provide ancillary services, including reserve power attained through down-regulating the wind farm from its...

  1. RT-40THE DOWN-REGULATION OF H-FERRITIN AS AN ADJUVANT THERAPY IN HUMAN GLIOMA

    OpenAIRE

    Pang, Min; Liu, Xiaoli; MadhanKumar, A.B.; Slagle-Webb, Becky; Connor, James

    2014-01-01

    Cancer cells generally exhibit increased iron requirements and heightened iron metabolism. As the major iron storage protein, ferritin expression is elevated in many types of cancer. In this study, we report that the sensitization of H-ferritin down-regulation in glioma cells against radiation and suggest the potential of H-ferritin down-regulation as an adjuvant therapy in human glioma. In human glioma cells, down-regulation of H-ferritin performed through a nanotechnology-based transfection...

  2. Oxytocin ameliorates the immediate myocardial injury in heart transplant through down regulation of the neutrophil dependent myocardial apoptosis

    Directory of Open Access Journals (Sweden)

    F Fadhil Al-Amran

    2014-01-01

    Conclusion: Oxytocin ameliorates myocardial injury in heart transplant through down-regulation the myocardial inflammatory response, reactive oxygen species, and neutrophil-dependant myocardial apoptosis.

  3. Ultraviolet Spectroscopy of Matrix-isolated Amorphous Carbon Particles

    Science.gov (United States)

    Schnaiter, M.; Mutschke, H.; Henning, Th.; Lindackers, D.; Strecker, M.; Roth, P.

    1996-06-01

    In view of the interstellar 217.5 nm and the circumstellar 230--250 nm extinction features, the UV extinction behavior of small matrix-isolated amorphous carbon grains is investigated experimentally. The particles were produced in a flame by burning acetylene with oxygen at low pressure. To prevent coagulation, the condensing primary soot grains (average diameter ~6 nm) were extracted by a molecular beam technique into a high-vacuum chamber. There they were deposited into a layer of solid argon, isolated from each other. The particle mass and size were controlled using a particle mass spectrometer. The measured UV extinction of the matrix-isolated particles is compared with measurements on samples produced in the conventional way by collecting carbon smoke on substrate as well as with scattering calculations for small spheres and ellipsoides. The laboratory data give a good representation of the circumstellar extinction feature observed in the spectrum of V348 Sgr.

  4. Down regulation of ribosomal protein mRNAs during neuronal differentiation of human NTERA2 cells.

    Science.gov (United States)

    Bévort, M; Leffers, H

    2000-10-01

    We have analysed the expression of 32 ribosomal protein (RP) mRNAs during retinoic acid induced neuronal differentiation of human NTERA2 cells. Except for a new S27 variant (S27v), all were down regulated both in selectively replated differentiated neurons and the most differentiated continuous cultures, i.e., non-replated cultures. However, the expression profiles of the individual RP mRNAs were different, most (L3, L7, L8, L10, L13, L23a, L27a, L36a, L39, P0, S2, S3, S3a, S4X, S6, S9, S12, S13, S16, S19, S20, S23, and S27a) exhibited a constant down regulation, whereas a few were either initially constant (L11, L32, S8, and S11) or up regulated (L6, L15, L17, L31, and S27y) and then down regulated. The expression of S27v remained elevated in the most differentiated continuous cultures but was down regulated in replated differentiated neurons. The down regulation of RP mRNAs was variable: the expression levels in differentiated replated neurons were between 10% (S3) and 90% (S11) of the levels in undifferentiated cells. The ratio between rRNA and RP mRNA changed during the differentiation; in differentiated neurons there were, on average, about half the number of RP mRNAs per rRNA as compared to undifferentiated cells. The expression profiles of a few translation-related proteins were also determined. EF1alpha1, EF1beta1, and EF1delta were down regulated, whereas the expression of the neuron and muscle specific EF1alpha2 increased. The reduction in the expression of RP mRNAs was coordinated with a reduction in the expression level of the proliferation marker PCNA. The expression levels of most RP mRNAs were lower in purified differentiated post-mitotic neurons than in the most differentiated continuous cultures, despite similar levels of PCNA, suggesting that both the differentiation state and the proliferative status of the cells affect the expression of RP mRNAs.

  5. Carbon in Comet Halley dust particles

    Science.gov (United States)

    Fomenkova, M. N.; Chang, S.

    1994-01-01

    Comets are small bodies of the solar system containing primarily a mixture of frozen gases and carbonaceous and mineral grains. They are likely to preserve volatile mineral from cold regions of the protosolar nebula and remnants of interstellar dust and gas. More than 2500 mass spectra of cometary grains with masses in the range 5 x 10 exp -17 to 5 x 10 exp -12 g were measured in situ by PUMA1 and PUMA2 mass spectrometers on board the VEGA spacecraft during flyby missions to Comet Halley. In this paper, we discuss different organic and inorganic C-containing components discovered so far in Comet Halley dust particles, the nature and abundance of which provide information about possible astrophysical sources of C and constrain models of interstellar grains.

  6. SAMHD1 is down regulated in lung cancer by methylation and inhibits tumor cell proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Jia-lei [Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032 (China); Lu, Fan-zhen [Department of Thoracic Surgery, The Huadong Hospital, Fudan University, Shanghai 200040 (China); Shen, Xiao-Yong, E-mail: shengxiaoyong_sh@163.com [Department of Thoracic Surgery, The Huadong Hospital, Fudan University, Shanghai 200040 (China); Wu, Yun, E-mail: WuYun_hd@163.com [Department of Thoracic Surgery, The Huadong Hospital, Fudan University, Shanghai 200040 (China); Zhao, Li-ting [Department of Thoracic Surgery, The Huadong Hospital, Fudan University, Shanghai 200040 (China)

    2014-12-12

    Highlights: • SAMHD1 expression level is down regulated in lung adenocarcinoma. • The promoter of SAMHD1 is methylated in lung adenocarcinoma. • Over expression of SAMHD1 inhibits the proliferation of lung cancer cells. - Abstract: The function of dNTP hydrolase SAMHD1 as a viral restriction factor to inhibit the replication of several viruses in human immune cells was well established. However, its regulation and function in lung cancer have been elusive. Here, we report that SAMHD1 is down regulated both on protein and mRNA levels in lung adenocarcinoma compared to adjacent normal tissue. We also found that SAMHD1 promoter is highly methylated in lung adenocarcinoma, which may inhibit its gene expression. Furthermore, over expression of the SAMHD1 reduces dNTP level and inhibits the proliferation of lung tumor cells. These results reveal the regulation and function of SAMHD1 in lung cancer, which is important for the proliferation of lung tumor cells.

  7. The Up- and Down-Regulation of Amusement:Experiential, Behavioral, and Autonomic Consequences

    OpenAIRE

    Giuliani, Nicole R.; McRae, Kateri; Gross, James J.

    2008-01-01

    A growing body of research has examined the regulation of negative emotions. However, little is known about the physiological processes underlying the regulation of positive emotions, such as when amusement is enhanced during periods of stress, or attenuated in the pursuit of social goals. The aim of this study was to examine the psychophysiological consequences of the cognitive up- and down-regulation of amusement. To address this goal, participants viewed brief, amusing film clips while mea...

  8. Down-Regulation of CD9 by Methylation Decreased Bortezomib Sensitivity in Multiple Myeloma

    OpenAIRE

    Xiaotong Hu; Han Xuan; Huaping Du; Hao Jiang; Jinwen Huang

    2014-01-01

    Bortezomib therapy has been proven successful for the treatment of relapsed and/or refractory multiple myeloma (MM). However, both intrinsic and acquired resistance has already been observed. In this study, we explored the relationship between CD9 expression and bortezomib sensitivity in MM. We found that down-regulation of CD9 by methylation decreased bortezomib sensitivity in multiple myeloma. CD9 expression obviously increased bortezomib sensitivity through inducing apoptosis, significantl...

  9. Natural Melanogenesis Inhibitors Acting Through the Down-Regulation of Tyrosinase Activity

    OpenAIRE

    Te-Sheng Chang

    2012-01-01

    Melanogenesis is a biosynthetic pathway for the formation of the pigment melanin in human skin. A key enzyme, tyrosinase, catalyzes the first and only rate-limiting steps in melanogenesis, and the down-regulation of enzyme activity is the most reported method for the inhibition of melanogenesis. Because of the cosmetically important issue of hyperpigmentation, there is a big demand for melanogenesis inhibitors. This encourages researchers to seek potent melanogenesis inhibitors for cosmetic u...

  10. A herbivorous mite down-regulates plant defence and produces web to exclude competitors.

    Directory of Open Access Journals (Sweden)

    Renato A Sarmento

    Full Text Available Herbivores may interact with each other through resource competition, but also through their impact on plant defence. We recently found that the spider mite Tetranychus evansi down-regulates plant defences in tomato plants, resulting in higher rates of oviposition and population growth on previously attacked than on unattacked leaves. The danger of such down-regulation is that attacked plants could become a more profitable resource for heterospecific competitors, such as the two-spotted spider mite Tetranychus urticae. Indeed, T. urticae had an almost 2-fold higher rate of oviposition on leaf discs on which T. evansi had fed previously. In contrast, induction of direct plant defences by T. urticae resulted in decreased oviposition by T. evansi. Hence, both herbivores affect each other through induced plant responses. However, when populations of T. evansi and T. urticae competed on the same plants, populations of the latter invariably went extinct, whereas T. evansi was not significantly affected by the presence of its competitor. This suggests that T. evansi can somehow prevent its competitor from benefiting from the down-regulated plant defence, perhaps by covering it with a profuse web. Indeed, we found that T. urticae had difficulties reaching the leaf surface to feed when the leaf was covered with web produced by T. evansi. Furthermore, T. evansi produced more web when exposed to damage or other cues associated with T. urticae. We suggest that the silken web produced by T. evansi serves to prevent competitors from profiting from down-regulated plant defences.

  11. cDNA suppression subtraction library for screening down-regulated genes in gastric carcinoma

    Institute of Scientific and Technical Information of China (English)

    Jian-Jun Du; Ke-Feng Dou; Shu-You Peng; Hua-Sheng Xiao; Wei-Zhong Wang; Wen-Xian Guan; Zhong-Hua Wang; Zhi-Qing Gao; Ying-Bin Liu

    2003-01-01

    AIM: To establish cDNA suppression subtraction library with a high subtraction efficiency by counterpart normal gastric mucosa mixture mRNA subtracting gastric cancer cells mixture mRNA for screening down-regulated genes in gastric carcinoma.METHODS: RNA of gastric cancer tissues and counterpart normal gastric mucosa were respectively isolated in five patients with gastric cancer, and their mRNA was purified.cDNA suppression subtraction library was established by counterpart normal gastric mucosa mixture mRNA (tester)subtracting gastric cancer tissues mixture mRNA (driver) of five patients with gastric carcinoma. The library plasmids were transformed into competent bacteria DH5a after ligation of the library cDNA fragments with T vectors. Library plasmids were extracted after picking colonies and shaking bacteria overnight. Its subtraction efficiency was confirmed by PCR and reverse hybridization of a nylon filter onto which the colonies of bacteria were transfered with probes of reverse transcription products cDNA of gastric cancer tissues mRNA and counterpart normal gastric mucosa mRNA labeled with α-32P dCTP.RESULTS: mRNA purified from total RNA of gastric cancer tissues and counterpart normal gastric mucosa in five patients with gastric carcinoma revealed a good quality. cDNA suppression subtraction library constructed for screening down-regulated genes in gastric carcinoma represented a high subtraction efficiency. 86 % of differential expression in down-regulated genes between counterpart normal gastric mucosa and gastric carcinoma was confirmed.CONCLUSION: cDNA suppression subtraction library with a high subtraction efficiency for screening down-regulated genes in gastric carcinoma is successfully established.

  12. Expression of NDRG2 is down-regulated in high-risk adenomas and colorectal carcinoma

    International Nuclear Information System (INIS)

    It has recently been shown that NDRG2 mRNA is down-regulated or undetectable in several human cancers and cancer cell-lines. Although the function of NDRG2 is unknown, high NDRG2 expression correlates with improved prognosis in high-grade gliomas. The aim of this study has been to examine NDRG2 mRNA expression in colon cancer. By examining affected and normal tissue from individuals with colorectal adenomas and carcinomas, as well as in healthy individuals, we aim to determine whether and at which stages NDRG2 down-regulation occurs during colonic carcinogenesis. Using quantitative RT-PCR, we have determined the mRNA levels for NDRG2 in low-risk (n = 15) and high-risk adenomas (n = 57), colorectal carcinomas (n = 50) and corresponding normal tissue, as well as control tissue from healthy individuals (n = 15). NDRG2 levels were normalised to β-actin. NDRG2 mRNA levels were lower in colorectal carcinomas compared to normal tissue from the control group (p < 0.001). When comparing adenomas/carcinomas with adjacent normal tissue from the same individual, NDRG2 expression levels were significantly reduced in both high-risk adenoma (p < 0.001) and in colorectal carcinoma (p < 0.001). There was a trend for NDRG2 levels to decrease with increasing Dukes' stage (p < 0.05). Our results demonstrate that expression of NDRG2 is down-regulated at a late stage during colorectal carcinogensis. Future studies are needed to address whether NDRG2 down-regulation is a cause or consequence of the progression of colorectal adenomas to carcinoma

  13. Top-down regulation of default mode activity in spatial visual attention

    OpenAIRE

    Wen, Xiaotong; Liu, Yijun; Yao, Li; Ding, Mingzhou

    2013-01-01

    Dorsal anterior cingulate and bilateral anterior insula form a task control network (TCN) whose primary function includes initiating and maintaining task-level cognitive set and exerting top-down regulation of sensorimotor processing. The default mode network (DMN), comprising an anatomically distinct set of cortical areas, mediates introspection and self-referential processes. Resting-state data show that TCN and DMN interact. The functional ramifications of their interaction remain elusive....

  14. Carbon dust particles in a beam-plasma discharge

    Science.gov (United States)

    Koval, O. A.; Vizgalov, V.; Shalpegin, A. V.

    2016-09-01

    This paper focuses on dynamics of micro-sized carbon dust grains in beam-plasma discharge (BPD) plasmas. It was demonstrated that injected dust particles can be captured and transported along the discharge. Longitudinal average velocity of the particles in the central area of the plasma column was 17 m/sec, and 2 m/sec in the periphery. Dust injection caused a decrease of emission intensity of metastable nitrogen molecular ion. This effect is suggested for a spectroscopy method for particles’ potential measurements. Five-micron radius carbon dust grains obtained potential above 500 V in the experiments on PR-2 installation, proving the feasibility of BPDs for the charging of fine dust particles up to high potential values, unattainable in similar plasma conditions.

  15. Nickel-induced down-regulation of serpin by hypoxic signaling

    International Nuclear Information System (INIS)

    Nickel (Ni) carcinogenesis is thought to involve gene chip silencing by epigenetic mechanisms. Serpina3g, a member of the mouse serpin family, was among the most down-regulated genes (32-fold) in response to Ni exposure of mouse cells based on the Affymetrix gene chip. Serpina3g down-regulation was controlled by a hypoxia inducible factor (HIF) mechanism. The exposure of cells to cobalt (Co), hypoxia, the iron chelator deferoxamine, and the proline hydroxylase inhibitor dimethyloxalylglycine (DMOG) also down-regulated serpina3g transcription to similar extents as soluble Ni exposure. These results support the mounting experimental evidence that water-soluble Ni compounds have a predominant effect on hypoxia signaling because of their ability to interfere with Fe homeostasis in the cell. Trichostatin A (TSA) and 5-azacytidine (5-AzaC) reactivated the Ni-silenced serpina3g gene, indicating that its silencing by Ni involved either a direct or indirect epigenetic mechanism. Analysis of the chromatin state of the serpina3g promoter by the ChIP assay revealed that exposure of mouse fibroblast cells to Ni resulted in the methylation of H3 lysine 9 within its promoter, as well as a decrease in the phosphorylation of serine 10 of H3 and a marked decrease in the acetylation of H3 and H4. Serpina3g gene expression returned to basal levels following Ni removal, suggesting that the observed silencing was a dynamic and reversible process

  16. Proteomic analysis of down-regulated proteins in colonic mucosa of chronic slow transit constipation rats

    Institute of Scientific and Technical Information of China (English)

    Wang Xingwei; Liu Haifeng; Xu Mei; Chen Gang; He Juntang; Wang Guoan; Teng Xiaochun; Fang Dianchun

    2009-01-01

    Objective: To investigate the alternations of proteins in the colonic mucosa of chronic slow transit constipation (STC) rats with a 2-DE-based proteomic method and analyze the function of these down-regulated proteins so as to provide theoretical basis for the pathogenesis of intestinal mucosa of chronic STC rats. Methods: STC model was established by feeding rats with 8 mg/(kg·d) diphenoxylate for 120 d. An experimental model of chronic STC rat was used for separation of proteomics from colonic mucosa using two-dimensional electrophoresis (2-DE). Proteins altered in expressional level were identified by Image Master 2DElite, mass spectrometry, and bibliometrics were applied to identify the differential protein expression and their clinical significance and function were analyzed. Results: Obvious differential protein expression was observed in the pathogenesis of STC, including mast cell protease (Al), non-specific dipeptidase (A2) and chondrosome succinate dehydrogenase precursor (A3). The expressions of Al, A2 and A3 were down-regulated in the gel graph of STC rats. Conclusion: The down-regulation of chondrosome succinate dehydrogenase, mast cell protease as well as non-specific dipeptidase in rat colon suggests the functional impairment of the oxidoreduction of mitochondrion is very important in the genesis and development of STC. The immunological reaction of STC rats is weakened, and the function of digesting and absorbing protein may be damaged to some extent.

  17. CHIP mediates down-regulation of nucleobindin-1 in preosteoblast cell line models.

    Science.gov (United States)

    Xue, Fuying; Wu, Yanping; Zhao, Xinghui; Zhao, Taoran; Meng, Ying; Zhao, Zhanzhong; Guo, Junwei; Chen, Wei

    2016-08-01

    Nucleobindin-1 (NUCB1), also known as Calnuc, is a highly conserved, multifunctional protein widely expressed in tissues and cells. It contains two EF-hand motifs which have been shown to play a crucial role in binding Ca(2+) ions. In this study, we applied comparative two-dimensional gel electrophoresis to characterize differentially expressed proteins in HA-CHIP over-expressed and endogenous CHIP depleted MC3T3-E1 stable cell lines, identifying NUCB1 as a novel CHIP/Stub1 targeted protein. NUCB1 interacts with and is down-regulated by CHIP by both proteasomal dependent and independent pathways, suggesting that CHIP-mediated down-regulation of nucleobindin-1 might play a role in osteoblast differentiation. The chaperone protein Hsp70 was found to be important for CHIP and NUCB1 interaction as well as CHIP-mediated NUCB1 down-regulation. Our findings provide new insights into understanding the stability regulation of NUCB1.

  18. Minibrain and Wings apart control organ growth and tissue patterning through down-regulation of Capicua.

    Science.gov (United States)

    Yang, Liu; Paul, Sayantanee; Trieu, Kenneth G; Dent, Lucas G; Froldi, Francesca; Forés, Marta; Webster, Kaitlyn; Siegfried, Kellee R; Kondo, Shu; Harvey, Kieran; Cheng, Louise; Jiménez, Gerardo; Shvartsman, Stanislav Y; Veraksa, Alexey

    2016-09-20

    The transcriptional repressor Capicua (Cic) controls tissue patterning and restricts organ growth, and has been recently implicated in several cancers. Cic has emerged as a primary sensor of signaling downstream of the receptor tyrosine kinase (RTK)/extracellular signal-regulated kinase (ERK) pathway, but how Cic activity is regulated in different cellular contexts remains poorly understood. We found that the kinase Minibrain (Mnb, ortholog of mammalian DYRK1A), acting through the adaptor protein Wings apart (Wap), physically interacts with and phosphorylates the Cic protein. Mnb and Wap inhibit Cic function by limiting its transcriptional repressor activity. Down-regulation of Cic by Mnb/Wap is necessary for promoting the growth of multiple organs, including the wings, eyes, and the brain, and for proper tissue patterning in the wing. We have thus uncovered a previously unknown mechanism of down-regulation of Cic activity by Mnb and Wap, which operates independently from the ERK-mediated control of Cic. Therefore, Cic functions as an integrator of upstream signals that are essential for tissue patterning and organ growth. Finally, because DYRK1A and CIC exhibit, respectively, prooncogenic vs. tumor suppressor activities in human oligodendroglioma, our results raise the possibility that DYRK1A may also down-regulate CIC in human cells. PMID:27601662

  19. Down-regulated miR-9 and miR-433 in human gastric carcinoma

    Directory of Open Access Journals (Sweden)

    Nie Na

    2009-06-01

    Full Text Available Abstract Background MircoRNAs(miRNAs are short, endogenously non-coding RNAs. The abnormal expression of miRNAs may be valuable for the diagnosis and treatment of tumors. Methods To screening the special miRNAs in gastric carcinoma, expression level of miRNAs in gastric carcinoma and normal gaster samples were detected by miRNA gene chip. Then, the expressions of miR-9 and miR-433 in gastric carcinoma tissue and SGC7901 cell line were validated by qRT-PCR. GRB2 and RAB34, targets of miR-433 and miR-9 respectively, were detected by Western blot. Results We found 19 miRNAs and 7 miRNAs were down-regulated and up-regulated respectively. Compared with normal gaster samples, our data showed that miR-9 and miR-433 were down-regulated in gastric carcinoma. Meanwhile, we also found that miR-433 and miR-9 regulated the expression levels of GRB2 and RAB34 respectively. Conclusion Our data show miR-9 and miR-433 was down-regulated in gastric carcinoma. The targets of miR-433 and miR-9 were tumor-associated proteins GRB2 and RAB34 respectively. This result provided the related information of miRNAs in gastric carcinoma.

  20. TCR Down-Regulation Controls Virus-Specific CD8+ T Cell Responses

    DEFF Research Database (Denmark)

    Bonefeld, Charlotte Menné; Haks, Mariëlle; Nielsen, Bodil;

    2008-01-01

    The CD3gamma di-leucine-based motif plays a central role in TCR down-regulation. However, little is understood about the role of the CD3gamma di-leucine-based motif in physiological T cell responses. In this study, we show that the expansion in numbers of virus-specific CD8(+) T cells is impaired...... in mice with a mutated CD3gamma di-leucine-based motif. The CD3gamma mutation did not impair early TCR signaling, nor did it compromise recruitment or proliferation of virus-specific T cells, but it increased the apoptosis rate of the activated T cells by increasing down-regulation of the...... antiapoptotic molecule Bcl-2. This resulted in a 2-fold reduction in the clonal expansion of virus-specific CD8(+) T cells during the acute phase of vesicular stomatitis virus and lymphocytic choriomeningitis virus infections. These results identify an important role of CD3gamma-mediated TCR down-regulation in...

  1. TCR down-regulation controls virus-specific CD8+ T cell responses

    DEFF Research Database (Denmark)

    Bonefeld, Charlotte Menné; Haks, Mariëlle; Nielsen, Bodil;

    2008-01-01

    The CD3gamma di-leucine-based motif plays a central role in TCR down-regulation. However, little is understood about the role of the CD3gamma di-leucine-based motif in physiological T cell responses. In this study, we show that the expansion in numbers of virus-specific CD8(+) T cells is impaired...... in mice with a mutated CD3gamma di-leucine-based motif. The CD3gamma mutation did not impair early TCR signaling, nor did it compromise recruitment or proliferation of virus-specific T cells, but it increased the apoptosis rate of the activated T cells by increasing down-regulation of the...... antiapoptotic molecule Bcl-2. This resulted in a 2-fold reduction in the clonal expansion of virus-specific CD8(+) T cells during the acute phase of vesicular stomatitis virus and lymphocytic choriomeningitis virus infections. These results identify an important role of CD3gamma-mediated TCR down-regulation in...

  2. Adipose Genes Down-Regulated During Experimental Endotoxemia Are Also Suppressed in Obesity

    Science.gov (United States)

    Hinkle, Christine C.; Haris, Lalarukh; Shah, Rhia; Mehta, Nehal N.; Putt, Mary E.; Reilly, Muredach P.

    2012-01-01

    Context: Adipose inflammation is a crucial link between obesity and its metabolic complications. Human experimental endotoxemia is a controlled model for the study of inflammatory cardiometabolic responses in vivo. Objective: We hypothesized that adipose genes down-regulated during endotoxemia would approximate changes observed with obesity-related inflammation and reveal novel candidates in cardiometabolic disease. Design, Subjects, and Intervention: Healthy volunteers (n = 14) underwent a 3 ng/kg endotoxin challenge; adipose biopsies were taken at 0, 4, 12, and 24 h for mRNA microarray. A priority list of highly down-regulated and biologically relevant genes was validated by RT-PCR in an independent sample of adipose from healthy subjects (n = 7) undergoing a subclinical 0.6 ng/kg endotoxemia protocol. Expression of validated genes was screened in adipose of lean and severely obese individuals (n = 11 per group), and cellular source was probed in cultured adipocytes and macrophages. Results: Endotoxemia (3 ng/kg) suppressed expression of 353 genes (to <67% of baseline; P < 1 × 10−5) of which 68 candidates were prioritized for validation. In low-dose (0.6 ng/kg) endotoxin validation, 22 (32%) of these 68 genes were confirmed. Functional classification revealed that many of these genes are involved in cell development and differentiation. Of validated genes, 59% (13 of 22) were down-regulated more than 1.5-fold in primary human adipocytes after treatment with endotoxin. In human macrophages, 59% (13 of 22) were up-regulated during differentiation to inflammatory M1 macrophages whereas 64% (14 of 22) were down-regulated during transition to homeostatic M2 macrophages. Finally, in obese vs. lean adipose, 91% (20 of 22) tended to have reduced expression (χ2 = 10.72, P < 0.01) with 50% (11 of 22) reaching P < 0.05 (χ2 = 9.28, P < 0.01). Conclusions: Exploration of down-regulated mRNA in adipose during human endotoxemia revealed suppression of genes involved in

  3. Erosion of carbon/carbon by solar wind charged particle radiation during a solar probe mission

    Science.gov (United States)

    Sokolowski, Witold; O'Donnell, Tim; Millard, Jerry

    1991-01-01

    The possible erosion of a carbon/carbon thermal shield by solar wind-charged particle radiation is reviewed. The present knowledge of erosion data for carbon and/or graphite is surveyed, and an explanation of erosion mechanisms under different charged particle environments is discussed. The highest erosion is expected at four solar radii. Erosion rates are analytically estimated under several conservative assumptions for a normal quiet and worst case solar wind storm conditions. Mass loss analyses and comparison studies surprisingly indicate that the predicted erosion rate by solar wind could be greater than by nominal free sublimation during solar wind storm conditions at four solar radii. The predicted overall mass loss of a carbon/carbon shield material during the critical four solar radii flyby can still meet the mass loss mission requirement of less than 0.0025 g/sec.

  4. Protein kinase C (PKC) alpha and PKC theta are the major PKC isotypes involved in TCR down-regulation

    DEFF Research Database (Denmark)

    von Essen, Marina; Nielsen, Martin W; Bonefeld, Charlotte M;

    2006-01-01

    It is well known that protein kinase C (PKC) plays an important role in regulation of TCR cell surface expression levels. However, eight different PKC isotypes are present in T cells, and to date the particular isotype(s) involved in TCR down-regulation remains to be identified. The aim...... of this study was to identify the PKC isotype(s) involved in TCR down-regulation and to elucidate the mechanism by which they induce TCR down-regulation. To accomplish this, we studied TCR down-regulation in the human T cell line Jurkat, in primary human T cells, or in the mouse T cell line DO11.10 in which we...... to induce significant TCR down-regulation. Both isotypes mediated TCR down-regulation via the TCR recycling pathway that strictly depends on Ser(126) and the di-leucine-based receptor-sorting motif of the CD3gamma chain. Finally, we found that PKCtheta was mainly implicated in down-regulation of directly...

  5. Protein kinase B/Akt1 inhibits autophagy by down-regulating UVRAG expression

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Wonseok; Ju, Ji-hyun; Lee, Kyung-min; Nam, KeeSoo; Oh, Sunhwa [Department of Life Science, College of Natural Science, Hanyang University, 17 Haengdang-dong, Seongdong-gu, Seoul 133-791 (Korea, Republic of); Shin, Incheol, E-mail: incheol@hanyang.ac.kr [Department of Life Science, College of Natural Science, Hanyang University, 17 Haengdang-dong, Seongdong-gu, Seoul 133-791 (Korea, Republic of)

    2013-02-01

    Autophagy, or autophagocytosis, is a selective intracellular degradative process involving the cell's own lysosomal apparatus. An essential component in cell development, homeostasis, repair and resistance to stress, autophagy may result in either cell death or survival. The targeted region of the cell is sequestered within a membrane structure, the autophagosome, for regulation of the catabolic process. A key factor in both autophagosome formation and autophagosome maturation is a protein encoded by the ultraviolet irradiation resistance-associated gene (UVRAG). Conversely, the serine/threonine-specific protein kinase B (PKB, also known as Akt), which regulates survival in various cancers, inhibits autophagy through mTOR activation. We found that Akt1 may also directly inhibit autophagy by down-regulating UVRAG both in a 293T transient transfection system and breast cancer cells stably expressing Akt1. The UVRAG with mutations at putative Akt1-phosphorylation sites were still inhibited by Akt1, and dominant-negative Akt1 also inhibited UVRAG expression, suggesting that Akt1 down-regulates UVRAG by a kinase activity-independent mechanism. We showed that Akt1 overexpression in MDA-MB-231 breast cancer cells down-regulated UVRAG transcription. Cells over-expressing Akt1 were more resistant than control cells to ultraviolet light-induced autophagy and exhibited the associated reduction in cell viability. Levels of the autophagosome indicator protein LC3B-II and mRFP-GFP-LC3 were reduced in cells that over-expressing Akt1. Inhibiting Akt1 by siRNA or reintroducing UVRAG gene rescued the level of LC3B-II in UV-irradiation. Altogether, these data suggest that Akt1 may inhibit autophagy by decreasing UVRAG expression, which also sensitizes cancer cells to UV irradiation.

  6. Curcumin and emodin down-regulate TGF-β signaling pathway in human cervical cancer cells.

    Directory of Open Access Journals (Sweden)

    Pooja Chandrakant Thacker

    Full Text Available Cervical cancer is the major cause of cancer related deaths in women, especially in developing countries and Human Papilloma Virus infection in conjunction with multiple deregulated signaling pathways leads to cervical carcinogenesis. TGF-β signaling in later stages of cancer is known to induce epithelial to mesenchymal transition promoting tumor growth. Phytochemicals, curcumin and emodin, are effective as chemopreventive and chemotherapeutic compounds against several cancers including cervical cancer. The main objective of this work was to study the effect of curcumin and emodin on TGF-β signaling pathway and its functional relevance to growth, migration and invasion in two cervical cancer cell lines, SiHa and HeLa. Since TGF-β and Wnt/β-catenin signaling pathways are known to cross talk having common downstream targets, we analyzed the effect of TGF-β on β-catenin (an important player in Wnt/β-catenin signaling and also studied whether curcumin and emodin modulate them. We observed that curcumin and emodin effectively down regulate TGF-β signaling pathway by decreasing the expression of TGF-β Receptor II, P-Smad3 and Smad4, and also counterbalance the tumorigenic effects of TGF-β by inhibiting the TGF-β-induced migration and invasion. Expression of downstream effectors of TGF-β signaling pathway, cyclinD1, p21 and Pin1, was inhibited along with the down regulation of key mesenchymal markers (Snail and Slug upon curcumin and emodin treatment. Curcumin and emodin were also found to synergistically inhibit cell population and migration in SiHa and HeLa cells. Moreover, we found that TGF-β activates Wnt/β-catenin signaling pathway in HeLa cells, and curcumin and emodin down regulate the pathway by inhibiting β-catenin. Taken together our data provide a mechanistic basis for the use of curcumin and emodin in the treatment of cervical cancer.

  7. Keratin 8 absence down-regulates colonocyte HMGCS2 and modulates colonic ketogenesis and energy metabolism.

    Science.gov (United States)

    Helenius, Terhi O; Misiorek, Julia O; Nyström, Joel H; Fortelius, Lina E; Habtezion, Aida; Liao, Jian; Asghar, M Nadeem; Zhang, Haiyan; Azhar, Salman; Omary, M Bishr; Toivola, Diana M

    2015-06-15

    Simple-type epithelial keratins are intermediate filament proteins important for mechanical stability and stress protection. Keratin mutations predispose to human liver disorders, whereas their roles in intestinal diseases are unclear. Absence of keratin 8 (K8) in mice leads to colitis, decreased Na/Cl uptake, protein mistargeting, and longer crypts, suggesting that keratins contribute to intestinal homeostasis. We describe the rate-limiting enzyme of the ketogenic energy metabolism pathway, mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2), as a major down-regulated protein in the K8-knockout (K8(-/-)) colon. K8 absence leads to decreased quantity and activity of HMGCS2, and the down-regulation is not dependent on the inflammatory state, since HMGCS2 is not decreased in dextran sulfate sodium-induced colitis. Peroxisome proliferator-activated receptor α, a transcriptional activator of HMGCS2, is similarly down-regulated. Ketogenic conditions-starvation or ketogenic diet-increase K8(+/+) HMGCS2, whereas this response is blunted in the K8(-/-) colon. Microbiota-produced short-chain fatty acids (SCFAs), substrates in the colonic ketone body pathway, are increased in stool, which correlates with decreased levels of their main transporter, monocarboxylate transporter 1 (MCT1). Microbial populations, including the main SCFA-butyrate producers in the colon, were not altered in the K8(-/-). In summary, the regulation of the SCFA-MCT1-HMGCS2 axis is disrupted in K8(-/-) colonocytes, suggesting a role for keratins in colonocyte energy metabolism and homeostasis. PMID:25904331

  8. Targeting γ-herpesvirus 68 Bcl-2-mediated down-regulation of autophagy.

    Science.gov (United States)

    Su, Minfei; Mei, Yang; Sanishvili, Ruslan; Levine, Beth; Colbert, Christopher L; Sinha, Sangita

    2014-03-21

    γ-herpesviruses (γHVs) are common human pathogens that encode homologs of the anti-apoptotic cellular Bcl-2 proteins, which are critical to viral reactivation and oncogenic transformation. The murine γHV68 provides a tractable in vivo model for understanding general features of these important human pathogens. Bcl-XL, a cellular Bcl-2 homolog, and the murine γHV68 Bcl-2 homolog, M11, both bind to a BH3 domain within the key autophagy effector Beclin 1 with comparable affinities, resulting in the down-regulation of Beclin 1-mediated autophagy. Despite this similarity, differences in residues lining the binding site of M11 and Bcl-XL dictate varying affinities for the different BH3 domain-containing proteins. Here we delineate Beclin 1 differential specificity determinants for binding to M11 or Bcl-XL by quantifying autophagy levels in cells expressing different Beclin 1 mutants and either M11 or Bcl-XL, and we show that a G120E/D121A Beclin 1 mutant selectively prevents down-regulation of Beclin 1-mediated autophagy by Bcl-XL, but not by M11. We use isothermal titration calorimetry to identify a Beclin 1 BH3 domain-derived peptide that selectively binds to M11, but not to Bcl-XL. The x-ray crystal structure of this peptide bound to M11 reveals the mechanism by which the M11 BH3 domain-binding groove accommodates this M11-specific peptide. This information was used to develop a cell-permeable peptide inhibitor that selectively inhibits M11-mediated, but not Bcl-XL-mediated, down-regulation of autophagy.

  9. Ciliary genes are down-regulated in bronchial tissue of primary ciliary dyskinesia patients.

    Directory of Open Access Journals (Sweden)

    Maciej Geremek

    Full Text Available Primary ciliary dyskinesia (PCD is a rare, genetically heterogeneous disease characterized by recurrent respiratory tract infections, sinusitis, bronchiectasis and male infertility. The pulmonary phenotype in PCD is caused by the impaired motility of cilia in the respiratory epithelium, due to ultrastructural defects of these organelles. We hypothesized that defects of multi-protein ciliary complexes should be reflected by gene expression changes in the respiratory epithelium. We have previously found that large group of genes functionally related to cilia share highly correlated expression pattern in PCD bronchial tissue. Here we performed an explorative analysis of differential gene expression in the bronchial tissue from six PCD patients and nine non-PCD controls, using Illumina HumanRef-12 Whole Genome BeadChips. We observed 1323 genes with at least 2-fold difference in the mean expression level between the two groups (t-test p-value <0.05. Annotation analysis showed that the genes down-regulated in PCD biopsies (602 were significantly enriched for terms related to cilia, whereas the up-regulated genes (721 were significantly enriched for terms related to cell cycle and mitosis. We assembled a list of human genes predicted to encode ciliary proteins, components of outer dynein arms, inner dynein arms, radial spokes, and intraflagellar transport proteins. A significant down-regulation of the expression of genes from all the four groups was observed in PCD, compared to non-PCD biopsies. Our data suggest that a coordinated down-regulation of the ciliome genes plays an important role in the molecular pathomechanism of PCD.

  10. Down-regulation of Wnt10a affects odontogenesis and proliferation in mesenchymal cells

    International Nuclear Information System (INIS)

    Highlights: •Down-regulation of Wnt10a in dental mesenchymal cells impairs odontogenesis of reassociated tooth germs. •Dspp is down- and up-regulated after Wnt10a-knockdown and overexpression in dental mesenchymal cells. •Down-regulation of Wnt10a inhibits proliferation of dental mesenchymal cells. -- Abstract: The WNT10a mutation has been found in patients with abnormal odontogenesis. In mice, Wnt10a expression is found in the tooth germ, but its role has not yet been elucidated. We aimed to investigate the role of Wnt10a in odontogenesis. Mesenchymal cells of the first mandibular molar germ at the bell stage were isolated, transfected with Wnt10a SiRNA or plasmid, and reassociated with epithelial part of the molar germ. Scrambled SiRNA or empty vector was used in the control group. The reassociated tooth germs were transplanted into mice subrenal capsules. After gene modification, dental mesenchymal cells cultured in vitro were checked for cell proliferation and the expression of Dspp was examined. All 12 reassociated tooth germs in the control group resumed odontogenesis, while only 5 of 12 in the Wnt10a knockdown group developed into teeth. After Wnt10a knockdown, the mesenchymal cells cultured in vitro presented repressed proliferation. Wnt10a knockdown and overexpression led to both down- and up-regulation of Dspp. We conclude that the down-regulation of Wnt10a impairs odontogensis and cell proliferation, and that Wnt10a regulates Dspp expression in mesenchymal cells. These findings help to elucidate the mechanism of abnormal tooth development in patients with the WNT10A mutation

  11. Down-regulation of Wnt10a affects odontogenesis and proliferation in mesenchymal cells

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Yang, E-mail: Ly10160624@163.com; Han, Dong, E-mail: Donghan@bjmu.edu.cn; Wang, Lei, E-mail: wanglei_dentist@163.com; Feng, Hailan, E-mail: kqfenghl@bjmu.edu.cn

    2013-05-17

    Highlights: •Down-regulation of Wnt10a in dental mesenchymal cells impairs odontogenesis of reassociated tooth germs. •Dspp is down- and up-regulated after Wnt10a-knockdown and overexpression in dental mesenchymal cells. •Down-regulation of Wnt10a inhibits proliferation of dental mesenchymal cells. -- Abstract: The WNT10a mutation has been found in patients with abnormal odontogenesis. In mice, Wnt10a expression is found in the tooth germ, but its role has not yet been elucidated. We aimed to investigate the role of Wnt10a in odontogenesis. Mesenchymal cells of the first mandibular molar germ at the bell stage were isolated, transfected with Wnt10a SiRNA or plasmid, and reassociated with epithelial part of the molar germ. Scrambled SiRNA or empty vector was used in the control group. The reassociated tooth germs were transplanted into mice subrenal capsules. After gene modification, dental mesenchymal cells cultured in vitro were checked for cell proliferation and the expression of Dspp was examined. All 12 reassociated tooth germs in the control group resumed odontogenesis, while only 5 of 12 in the Wnt10a knockdown group developed into teeth. After Wnt10a knockdown, the mesenchymal cells cultured in vitro presented repressed proliferation. Wnt10a knockdown and overexpression led to both down- and up-regulation of Dspp. We conclude that the down-regulation of Wnt10a impairs odontogensis and cell proliferation, and that Wnt10a regulates Dspp expression in mesenchymal cells. These findings help to elucidate the mechanism of abnormal tooth development in patients with the WNT10A mutation.

  12. The Mycobacterium tuberculosis H37Ra gene MRA_1916 causes growth defects upon down-regulation

    OpenAIRE

    Kumar Sachin Singh; Sudheer Kumar Singh

    2015-01-01

    D-amino acid oxidases play an important role in converting D-amino acids to their corresponding α-keto acids. MRA_1916 of Mycobacterium tuberculosis H37Ra (Mtb-Ra) is annotated to be a D-amino acid oxidase (DAO). However, not much information is available about its physiological role during Mtb-Ra growth and survival. The present study was taken-up to understand the role of DAO during different stages of growth and effect of its down-regulation on growth. Recombinant Mtb-Ra strains with DAO a...

  13. EGFRvIII escapes down-regulation due to impaired internalization and sorting to lysosomes

    DEFF Research Database (Denmark)

    Grandal, Michael V; Zandi, Roza; Pedersen, Mikkel W;

    2007-01-01

    signaling pathways. Failure to attenuate signaling by receptor down-regulation could be one of the major mechanisms by which EGFRvIII becomes oncogenic. Using a cell system expressing either EGFR or EGFRvIII with no expression of other EGFR family members and with endogenous levels of key degradation....... Moreover, internalized EGFRvIII is recycled rather than delivered to lysosomes. EGFRvIII binds the ubiquitin ligase c-Cbl via Grb2, whereas binding via phosphorylated tyrosine residue 1045 seems to be limited. Despite c-Cbl binding, the receptor fails to become effectively ubiquitinylated. Thus, our...

  14. Carcinogen inducibility in vivo and down-regulation of DMBT1 during breast carcinogenesis

    DEFF Research Database (Denmark)

    Mollenhauer, Jan; Helmke, Burkhard; Medina, Daniel;

    2004-01-01

    unambiguous inactivating DMBT1 mutations in breast cancer. Expression analyses in the human and mouse mammary glands pointed to the necessity of DMBT1 induction. While age-dependent and hormonal effects could be ruled out, 9 of 10 mice showed induction of Dmbt1 expression after administration...... of the carcinogen 7,12-dimethybenz(alpha)anthracene prior to the onset of tumorigenesis or other histopathological changes. DMBT1 displayed significant up-regulation in human tumor-flanking tissues compared to in normal breast tissues (P ... secretion to secretion to the extracellular matrix and a significant down-regulation compared to that in matched normal flanking tissues (P

  15. Down-regulation of protein kinase Ceta by antisense oligonucleotides sensitises A549 lung cancer cells to vincristine and paclitaxel.

    Science.gov (United States)

    Sonnemann, Jürgen; Gekeler, Volker; Ahlbrecht, Katrin; Brischwein, Klaus; Liu, Chao; Bader, Peter; Müller, Cornelia; Niethammer, Dietrich; Beck, James F

    2004-06-25

    Previous studies point to protein kinase C (PKC) isozyme eta as a resistance factor in cancer cells. Therefore, we investigated whether down-regulation of PKCeta with second generation antisense oligonucleotides (ODNs) would sensitise A549 human lung carcinoma cells to cytostatics. The effects were compared to the outcome of Bcl-xL down-regulation. Upon treatment with antisense ODNs, PKCeta and Bcl-xL were both significantly reduced on mRNA and protein level. Down-regulation of either PKCeta or Bcl-xL in combination with vincristine or paclitaxel resulted in a significant increase in caspase-3 activity compared to that in the control oligonucleotide treated cells. In addition, PKCeta down-regulation augmented vincristine-induced dissipation of mitochondrial transmembrane potential. In conclusion, these results confirm that PKCeta might represent a considerable resistance factor and an interesting target to improve anticancer chemotherapy. PMID:15159020

  16. Down-regulation of Runx1 Expression by TCR Signal Involves an Autoregulatory Mechanism and Contributes to IL-2 Production*

    OpenAIRE

    Wong, Won Fen; Kurokawa, Mineo; Satake, Masanobu; Kohu, Kazuyoshi

    2011-01-01

    Runx1 transcription factor plays multiple roles in T cell development, differentiation, and function. However, the regulatory mechanisms and functional significance of high Runx1 protein expression in resting peripheral CD4+ T cells is not well understood. Here, we demonstrate that T-cell receptor (TCR) activation down-regulates distal Runx1 transcription, resulting in a significant reduction of Runx1 protein. Interestingly, this down-regulation of distal Runx1 transcription appears to be med...

  17. Muscarinic acetylcholine receptor down-regulation limits the extent of inhibition of cell cycle progression in Chinese hamster ovary cells.

    OpenAIRE

    Detjen, K.; Yang, J; Logsdon, C D

    1995-01-01

    Cellular desensitization is believed to be important for growth control but direct evidence is lacking. In the current study we compared effects of wild-type and down-regulation-resistant mutant m3 muscarinic receptors on Chinese hamster ovary (CHO-K1) cell desensitization, proliferation, and transformation. We found that down-regulation of m3 muscarinic acetylcholine receptors was the principal mechanism of desensitization of receptor-activated inositol phosphate phospholipid hydrolysis in t...

  18. Ischemic preconditioning acts upstream of GluR2 down-regulation to afford neuroprotection in the hippocampal CA1

    OpenAIRE

    Tanaka, Hidenobu; Calderone, Agata; Jover, Teresa; Grooms, Sonja Y.; Yokota, Hidenori; Zukin, R. Suzanne; Bennett, Michael V. L.

    2002-01-01

    Animals subjected to sublethal transient global ischemia (ischemic preconditioning) exhibit neuroprotection against subsequent global ischemia-induced neuronal death in the hippocampal CA1 (ischemic tolerance). The molecular mechanisms underlying ischemic tolerance are unclear. Here we report that ischemic preconditioning induced a small, transient down-regulation of GluR2 mRNA expression and greatly attenuated subsequent ischemia-induced GluR2 mRNA and protein down-regulation and neuronal de...

  19. Down-regulation of p73 correlates with high histological grade in Japanese with breast carcinomas

    Institute of Scientific and Technical Information of China (English)

    DU Cai-wen; Izo Kimijima; Toru Otake; Rikiya Abe; Seiichi Takenoshita; ZHANG Guo-jun

    2011-01-01

    Background p73, a homologue of p53, has been located at chromosome 1 p36-33, a region of frequently observed loss of heterozygosity in breast cancers. The objective of the present study was to investigate the function of p73 in Japanese with breast cancers. Methods Sixty Japanese patients with breast cancer were assessed by polymerase chain reaction single strand confirmation polymorphism analysis and direct sequencing to detect the p73 allele. p73 mRNA levels were also determined in 40 out of 60 patients by reverse-transcriptional polymerase chain reaction. Results We analyzed the entire open reading frame of the p73 gene by polymerase chain reaction single strand confirmation polymorphism and sequencing, and failed to identify any mutations of p73 in the encoding regions detected.Loss of heterozygosity of p73 was infrequent and only found in 9% of breast carcinomas. We revealed a few polymorphisms with a frequency of 13%-29%, which had been reported previously. Down-regulation of p73 mRNA expression was observed in tumor tissues in comparison to the normal breast tissues. A significant inverse correlation was found between p73 transcripts and high histological grade, suggesting that down-regulated p73 expression could be related to poor prognosis in those patients. Conclusion Our results suggest that p73 may serve as a tumor suppressor gene and its expression plays a role in tumorigenesis in Japanese patients with breast cancer.

  20. Protamine sulfate down-regulates thrombin generation by inhibiting factor V activation.

    LENUS (Irish Health Repository)

    Ni Ainle, Fionnuala

    2009-08-20

    Protamine sulfate is a positively charged polypeptide widely used to reverse heparin-induced anticoagulation. Paradoxically, prospective randomized trials have shown that protamine administration for heparin neutralization is associated with increased bleeding, particularly after cardiothoracic surgery with cardiopulmonary bypass. The molecular mechanism(s) through which protamine mediates this anticoagulant effect has not been defined. In vivo administration of pharmacologic doses of protamine to BALB\\/c mice significantly reduced plasma thrombin generation and prolonged tail-bleeding time (from 120 to 199 seconds). Similarly, in pooled normal human plasma, protamine caused significant dose-dependent prolongations of both prothrombin time and activated partial thromboplastin time. Protamine also markedly attenuated tissue factor-initiated thrombin generation in human plasma, causing a significant decrease in endogenous thrombin potential (41% +\\/- 7%). As expected, low-dose protamine effectively reversed the anticoagulant activity of unfractionated heparin in plasma. However, elevated protamine concentrations were associated with progressive dose-dependent reduction in thrombin generation. To assess the mechanism by which protamine mediates down-regulation of thrombin generation, the effect of protamine on factor V activation was assessed. Protamine was found to significantly reduce the rate of factor V activation by both thrombin and factor Xa. Protamine mediates its anticoagulant activity in plasma by down-regulation of thrombin generation via a novel mechanism, specifically inhibition of factor V activation.

  1. microRNA-143 down-regulates Hexokinase 2 in colon cancer cells

    DEFF Research Database (Denmark)

    Gregersen, Lea Haarup; Jacobsen, Anders; Frankel, Lisa;

    2012-01-01

    -regulated in several cancers including colon cancer. METHODS: To gain insight into the role of miR-143 in colon cancer, we used a microarray-based approach in combination with seed site enrichment analysis to identify miR-143 targets. RESULTS: As expected, transcripts down-regulated upon miR-143 overexpression had...... a significant enrichment of miR-143 seed sites in their 3' UTRs. Here we report the identification of Hexokinase 2 (HK2) as a direct target of miR-143. We show that re-introduction of miR-143 in the colon cancer cell line DLD-1 results in a decreased lactate secretion. CONCLUSION: We have identified...... and validated HK2 as a miR-143 target. Furthermore, our results indicate that miR-143 mediated down-regulation of HK2 affects glucose metabolism in colon cancer cells. We hypothesize that loss of miR-143-mediated repression of HK2 can promote glucose metabolism in cancer cells, contributing to the shift towards...

  2. Down-Regulated MAC30 Expression Inhibits Proliferation and Mobility of Human Gastric Cancer Cells

    Directory of Open Access Journals (Sweden)

    Xiao-Yan Xu

    2014-05-01

    Full Text Available Background: Gastric cancer is one of the most common cancers in the world. MAC30/Transmembrane protein 97 (TMEM97 is aberrantly up-regulated in many human carcinoma cells. However, the function of MAC30 in gastric carcinoma cells is not studied. Material and Methods: To investigate the function of MAC30 in gastric carcinoma, we used RNA silencing technology to knock down the expression of MAC30 in gastric cancer cells BGC-823 and AGS. Real-time quantitative PCR and Western blot were used to analyze the mRNA level and the related protein expression. The localization of MAC30 and lamellipodia was observed by immunofluorescence. The biological phenotypes of gastric cells were examined by cell proliferation assay, cell cycle analysis, apoptosis assay, cell migration and invasion assay. Results: We found that down-regulation of MAC30 expression efficiently inhibited the proliferation of gastric cancer cells. Furthermore, the mobility of gastric cancer cells was also inhibited by down-regulation of MAC30. Moreover, we found that MAC30 knockdown inhibited AKT phosphorylation and reduced the expression of cyclinB1 and WAVE2. Conclusion: To our knowledge, this is the first report investigating the effect of MAC30 on growth, cell cycle, migration, and invasion in gastric carcinoma cells via suppressing AKT signaling pathway. MAC30 may be a potential therapeutic target for treatment of gastric carcinoma.

  3. Down-regulation of Rab5 decreases characteristics associated with maintenance of cell transformation

    International Nuclear Information System (INIS)

    The early endosomal protein Rab5 is highly expressed in tumor samples, although a causal relationship between Rab5 expression and cell transformation has not been established. Here, we report the functional effects of targeting endogenous Rab5 with specific shRNA sequences in different tumor cell lines. Rab5 down-regulation in B16-F10 cells decreased tumor formation by subcutaneous injection into C57/BL6 mice. Accordingly, Rab5 targeting in B16-F10 and A549, but not MDA-MB-231 cells was followed by decreased cell proliferation, increased apoptosis and decreased anchorage-independent growth. These findings suggest that Rab5 expression is required to maintain characteristics associated with cell transformation. - Highlights: • Rab5 is important to the maintenance of cell transformation characteristics. • Down-regulation of Rab5 decreases cell proliferation and increases apoptosis in different cancer cells. • Rab5 is required for anchorage-independent growth and tumorigenicity in-vivo

  4. Down-regulation of Rab5 decreases characteristics associated with maintenance of cell transformation

    Energy Technology Data Exchange (ETDEWEB)

    Silva, Patricio; Soto, Nicolás [Institute for Research in Dental Sciences, Faculty of Dentistry, Universidad de Chile, Santiago (Chile); Díaz, Jorge [Institute for Research in Dental Sciences, Faculty of Dentistry, Universidad de Chile, Santiago (Chile); Center for Molecular Studies of the Cell, Institute of Biomedical Sciences (ICBM), Faculty of Medicine, Universidad de Chile, Santiago (Chile); Mendoza, Pablo [Institute for Research in Dental Sciences, Faculty of Dentistry, Universidad de Chile, Santiago (Chile); Díaz, Natalia [Institute for Research in Dental Sciences, Faculty of Dentistry, Universidad de Chile, Santiago (Chile); Center for Molecular Studies of the Cell, Institute of Biomedical Sciences (ICBM), Faculty of Medicine, Universidad de Chile, Santiago (Chile); Quest, Andrew F.G. [Center for Molecular Studies of the Cell, Institute of Biomedical Sciences (ICBM), Faculty of Medicine, Universidad de Chile, Santiago (Chile); Advanced Center for Chronic Diseases (ACCDiS), Faculty of Medicine, Universidad de Chile, Santiago (Chile); Torres, Vicente A., E-mail: vatorres@med.uchile.cl [Institute for Research in Dental Sciences, Faculty of Dentistry, Universidad de Chile, Santiago (Chile); Advanced Center for Chronic Diseases (ACCDiS), Faculty of Medicine, Universidad de Chile, Santiago (Chile)

    2015-08-21

    The early endosomal protein Rab5 is highly expressed in tumor samples, although a causal relationship between Rab5 expression and cell transformation has not been established. Here, we report the functional effects of targeting endogenous Rab5 with specific shRNA sequences in different tumor cell lines. Rab5 down-regulation in B16-F10 cells decreased tumor formation by subcutaneous injection into C57/BL6 mice. Accordingly, Rab5 targeting in B16-F10 and A549, but not MDA-MB-231 cells was followed by decreased cell proliferation, increased apoptosis and decreased anchorage-independent growth. These findings suggest that Rab5 expression is required to maintain characteristics associated with cell transformation. - Highlights: • Rab5 is important to the maintenance of cell transformation characteristics. • Down-regulation of Rab5 decreases cell proliferation and increases apoptosis in different cancer cells. • Rab5 is required for anchorage-independent growth and tumorigenicity in-vivo.

  5. Curcumin down-regulates AR gene expression and activation in prostate cancer cell lines.

    Science.gov (United States)

    Nakamura, Keiichiro; Yasunaga, Yutaka; Segawa, Takehiko; Ko, Daejin; Moul, Judd W; Srivastava, Shiv; Rhim, Johng S

    2002-10-01

    Curcumin, traditionally used as a seasoning spice in Indian cuisine, has been reported to decrease the proliferation potential of prostate cancer cells, by a mechanism that is not fully understood. In the current study, we have evaluated the effects of curcumin in cell growth, activation of signal transduction, and transforming activities of both androgen-dependent and independent cell lines. Prostate cancer cell lines, LNCaP and PC-3, were treated with curcumin and its effects were further analyzed on signal transduction and expression of androgen receptor (AR) and AR-related cofactors using transient transfection assay and Western blotting. Our results show that curcumin down-regulates transactivation and expression of AR, activator protein-1 (AP-1), nuclear factor-kappaB (NF-kappaB), and CREB (cAMP response element-binding protein)-binding protein (CBP). Curcumin also inhibited the transforming activities of both cell lines as evidenced by the reduced colony forming ability in soft agar. The results obtained here demonstrate that curcumin has a potential therapeutic effect on prostate cancer cells through down-regulation of AR and AR-related cofactors (AP-1, NF-kappaB and CBP). PMID:12239622

  6. Neuritin is expressed in Schwann cells and down-regulated in apoptotic Schwann cells under hyperglycemia.

    Science.gov (United States)

    Min, Shi; Jian-bo, Li; Hong-man, Zhang; Ling-fei, Yan; Min, Xie; Jia-wei, Chen

    2012-11-01

    We aimed to explore neuritin expression in Schwann cells under different glucose conditions. Expression of neuritin at the levels of transcription and translation in purified Schwann cells was detected and measured using reverse transcriptase (RT) (quantitative) polymerase chain reaction (PCR) and western blot. Apoptosis of Schwann cells was measured by flow cytometry using Fluorescence Activated Cell Sorter (FACS) analysis and caspase fluorometric assay. Neuritin mRNA and protein were detected in cultured primary Schwann cells. Neuritin was identified as cell membrane form of protein and predominately as secreted or solube form of protein. Neuritin was significantly lower in 150 mM glucose condition, and more significantly lower in 300 mM glucose, than 5.6 mM glucose condition at 36 hours and especially at 48 hours of the culture, respectively (P Neuritin and apoptosis were correlated in a power regression (P neuritin mRNA and protein were expressed and down-regulated in Schwann cells under high-glucose concentration and the down-regulation may contribute to apopotosis of Schwann cells. PMID:22782233

  7. Down-Regulation of Lipocalin 2 Expression in Mouse Testis after Exposure to Electromagnetic Field

    Directory of Open Access Journals (Sweden)

    Amaneh Mohammadi Roushandeh

    2009-12-01

    Full Text Available Background: The effects of electromagnetic field (EMF onreproductive system have been of critical concern for a longtime. It has been shown that the EMF can adversely affect testicularcells and tissue and decrease male fertility. The mostimportant determinants of male fertility are sperm developmentand motility, which are affected by changes in several factorsincluding lipocalin 2 proteins. In the present study, we investigatedthe effects of exposure to EMF on testis tissue and expressionof lipocalin 2 gene.Methods: Male BALB/c mice (8 weeks old were exposed to 3mT EMF for 8 weeks, 4 hours/day. Control group (10 micedid not receive EMF exposure. After the experimental period,the mice were sacrificed, and their testis tissues were examinedby using light microscopy after hematoxylin-eosin staining.Additionally, total RNA and proteins were extracted from testistissue and used to study the lipocalin 2 expression by realtime RT-PCR and Western blot analysis.Results: The histological changes observed in the testes of experimentalgroup included increased number of spermatocytesand Leydig cells, and increased thickness of basement membranecompared with the control group. The mRNA and proteinstudies showed that expression of lipocalin 2 gene wasdown regulated in testes of the mice exposed to EMF.Conclusion: Our study showed that EMF down regulates theexpression of lipocalin 2, a cytoprotective molecule, in testis tissue.This down regulation can be one of the mechanisms that contributeto the decreased fertility observed after exposure to EMF

  8. Effects of p21 Gene Down-Regulation through RNAi on Antler Stem Cells In Vitro.

    Directory of Open Access Journals (Sweden)

    Qianqian Guo

    Full Text Available Cell cycle is an integral part of cell proliferation, and consists mainly of four phases, G1, S, G2 and M. The p21 protein, a cyclin dependent kinase inhibitor, plays a key role in regulating cell cyclevia G1 phase control. Cells capable of epimorphic regeneration have G2/M accumulation as their distinctive feature, whilst the majority of somatic cells rest at G1 phase. To investigate the role played byp21 in antler regeneration, we studied the cell cycle distribution of antler stem cells (ASCs, via down-regulation of p21 in vitro using RNAi. The results showed that ASCs had high levels of p21 mRNA expression and rested at G1 phase, which was comparable to the control somatic cells. Down-regulation of p21 did not result in ASC cell cycle re-distribution toward G2/M accumulation, but DNA damage and apoptosis of the ASCs significantly increased and the process of cell aging was slowed. These findings suggest that the ASCs may have evolved to use an alternative, p21-independent cell cycle regulation mechanism. Also a unique p21-dependent inhibitory effect may control DNA damage as a protective mechanism to ensure the fast proliferating ASCs do not become dysplastic/cancerous. Understanding of the mechanism underlying the role played by p21 in the ASCs could give insight into a mammalian system where epimorphic regeneration is initiated whilst the genome stability is effectively maintained.

  9. Effects of p21 Gene Down-Regulation through RNAi on Antler Stem Cells In Vitro.

    Science.gov (United States)

    Guo, Qianqian; Wang, Datao; Liu, Zhen; Li, Chunyi

    2015-01-01

    Cell cycle is an integral part of cell proliferation, and consists mainly of four phases, G1, S, G2 and M. The p21 protein, a cyclin dependent kinase inhibitor, plays a key role in regulating cell cyclevia G1 phase control. Cells capable of epimorphic regeneration have G2/M accumulation as their distinctive feature, whilst the majority of somatic cells rest at G1 phase. To investigate the role played byp21 in antler regeneration, we studied the cell cycle distribution of antler stem cells (ASCs), via down-regulation of p21 in vitro using RNAi. The results showed that ASCs had high levels of p21 mRNA expression and rested at G1 phase, which was comparable to the control somatic cells. Down-regulation of p21 did not result in ASC cell cycle re-distribution toward G2/M accumulation, but DNA damage and apoptosis of the ASCs significantly increased and the process of cell aging was slowed. These findings suggest that the ASCs may have evolved to use an alternative, p21-independent cell cycle regulation mechanism. Also a unique p21-dependent inhibitory effect may control DNA damage as a protective mechanism to ensure the fast proliferating ASCs do not become dysplastic/cancerous. Understanding of the mechanism underlying the role played by p21 in the ASCs could give insight into a mammalian system where epimorphic regeneration is initiated whilst the genome stability is effectively maintained.

  10. Down-regulation of MiR-127 facilitates hepatocyte proliferation during rat liver regeneration.

    Directory of Open Access Journals (Sweden)

    Chuanyong Pan

    Full Text Available Liver regeneration (LR after partial hepatectomy (PH involves the proliferation and apoptosis of hepatocytes, and microRNAs have been shown to post-transcriptionally regulate genes involved in the regulation of these processes. To explore the role of miR-127 during LR, the expression patterns of miR-127 and its related proteins were investigated. MiR-127 was introduced into a rat liver cell line to examine its effects on the potential target genes Bcl6 and Setd8, and functional studies were undertaken. We discovered that miR-127 was down-regulated and inversely correlated with the expression of Bcl6 and Setd8 at 24 hours after PH, a time at which hypermethylation of the promoter region of the miR-127 gene was detected. Furthermore, in BRL-3A rat liver cells, we observed that overexpression of miR-127 significantly suppressed cell growth and directly inhibited the expression of Bcl6 and Setd8. The results suggest that down-regulation of miR-127 may be due to the rapid methylation of its promoter during the first 24 h after PH, and this event facilitates hepatocyte proliferation by releasing Bcl6 and Setd8. These findings support a miRNA-mediated negative regulation pattern in LR and implicate an anti-proliferative role for miR-127 in liver cells.

  11. Down-regulation of tissue N:P ratios in terrestrial plants by elevated CO2.

    Science.gov (United States)

    Deng, Qi; Hui, Dafeng; Luo, Yiqi; Elser, James; Wang, Ying-ping; Loladze, Irakli; Zhang, Quanfa; Dennis, Sam

    2015-12-01

    Increasing atmospheric CO2 concentrations generally alter element stoichiometry in plants. However, a comprehensive evaluation of the elevated CO2 impact on plant nitrogen: phosphorus (N:P) ratios and the underlying mechanism has not been conducted. We synthesized the results from 112 previously published studies using meta-analysis to evaluate the effects of elevated CO2 on the N:P ratio of terrestrial plants and to explore the underlying mechanism based on plant growth and soil P dynamics. Our results show that terrestrial plants grown under elevated CO2 had lower N:P ratios in both above- and belowground biomass across different ecosystem types. The response ratio for plant N:P was negatively correlated with the response ratio for plant growth in croplands and grasslands, and showed a stronger relationship for P than for N. In addition, the CO2-induced down-regulation of plant N:P was accompanied by 19.3% and 4.2% increases in soil phosphatase activity and labile P, respectively, and a 10.1% decrease in total soil P. Our results show that down-regulation of plant N:P under elevated CO2 corresponds with accelerated soil P cycling. These findings should be useful for better understanding of terrestrial plant stoichiometry in response to elevated CO2 and of the underlying mechanisms affecting nutrient dynamics under climate change.

  12. Phosphorylation-dependent down-regulation of apolipoprotein A5 by insulin

    Energy Technology Data Exchange (ETDEWEB)

    Nowak, Maxine; Helleboid-Chapman, Audrey; Jakel, Heidelinde; Rommens, Corinne; Martin, Genevieve; Duran-Sandoval, Daniel; Staels, Bart; Rubin, Edward M.; Pennacchio, Len A.; Taskinen, Marja-Riitta; Fruchart-Najib, Jamila; Fruchart, Jean-Charles

    2004-02-15

    The apolipoprotein A5 (APOA5) gene has been shown to be important in lowering plasma triglyceride levels. Since several studies have shown that hyperinsulinemia is associated with hypertriglyceridemia, we sought to determine whether APOA5 gene is regulated by insulin. We show here that cell and mouse treatments with insulin down-regulated APOA5 expression in a dose-dependent manner. Furthermore, we determined that insulin decreases APOA5 promoter activity and subsequent deletion analyses revealed an E-box-containing fragment. We showed that Upstream Stimulatory Factors, USF1/USF2, bind to the identified E-box in the APOA5 promoter. Moreover, in cotransfection studies, USF1 stimulates APOA5 promoter activity. The treatment with insulin reduces the binding of USF1/USF2 to APOA5 promoter. The inhibition of PI3K pathway with wortmannin abolished the insulin s effect on APOA5 gene transcription. Using oligoprecipitation method of USF from nuclear extracts, we demonstrated that phosphorylated USF1 failed to bind to APOA5 promoter. This indicates that the APOA5 gene transrepression by insulin involves a phosphorylation of USF through PI3K, that modulate their binding to APOA5 promoter and results in APOA5 down-regulation. The effect of exogenous hyperinsulinemia in healthy men shows a decrease of the plasma ApoAV level. These data suggest a potential mechanism involving APOA5 gene in hypertriglyceridemia associated with hyperinsulinemia.

  13. Tolerization with BLP down-regulates HMGB1 a critical mediator of sepsis-related lethality.

    LENUS (Irish Health Repository)

    Coffey, J Calvin

    2012-02-03

    Tolerization with bacterial lipoprotein (BLP) affords a significant survival benefit in sepsis. Given that high mobility group box protein-1 (HMGB1) is a recognized mediator of sepsis-related lethality, we determined if tolerization with BLP leads to alterations in HMGB1. In vitro, BLP tolerization led to a reduction in HMGB1 gene transcription. This was mirrored at the protein level, as HMGB1 protein expression and release were reduced significantly in BLP-tolerized human THP-1 monocytic cells. BLP tolerance in vivo led to a highly significant, long-term survival benefit following challenge with lethal dose BLP in C57BL\\/6 mice. This was associated with an attenuation of HMGB1 release into the circulation, as evidenced by negligible serum HMGB1 levels in BLP-tolerized mice. Moreover, HMGB1 levels in peritoneal macrophages from BLP-tolerized mice were reduced significantly. Hence, tolerization with BLP leads to a down-regulation of HMGB1 protein synthesis and release. The improved survival associated with BLP tolerance could thus be explained by a reduction in HMGB1, were the latter associated with lethality in BLP-related sepsis. In testing this hypothesis, it was noted that neutralization of HMGB1, using anti-HMGB1 antibodies, abrogated BLP-associated lethality almost completely. To conclude, tolerization with BLP leads to a down-regulation of HMGB1, thus offering a novel means of targeting the latter. HMGB1 is also a mediator of lethality in BLP-related sepsis.

  14. Characterization of calcium carbonate sorbent particle in furnace environment

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Kang Soo [Aerosol and Particle Technology Laboratory, Department of Mechanical Engineering, KAIST 291 Daehak-ro, Yuseong-gu, Daejeon, 305-701 (Korea, Republic of); Jung, Jae Hee [Environment Sensor System Research Center, KIST 39-1 Hawolgok-dong, Seongbuk-gu, Seoul, 136-791 (Korea, Republic of); Keel, Sang In; Yun, Jin Han; Min, Tai Jin [Environmental Systems Research Division, KIMM 104 Sinseongno, Yuseong-gu, Daejeon, 305-343 (Korea, Republic of); Kim, Sang Soo, E-mail: sskim@kaist.ac.kr [Aerosol and Particle Technology Laboratory, Department of Mechanical Engineering, KAIST 291 Daehak-ro, Yuseong-gu, Daejeon, 305-701 (Korea, Republic of)

    2012-07-01

    The oxy-fuel combustion system is a promising technology to control CO{sub 2} and NO{sub X} emissions. Furthermore, sulfation reaction mechanism under CO{sub 2}-rich atmospheric condition in a furnace may lead to in-furnace desulfurization. In the present study, we evaluated characteristics of calcium carbonate (CaCO{sub 3}) sorbent particles under different atmospheric conditions. To examine the physical/chemical characteristics of CaCO{sub 3}, which is used as a sorbent particle for in-furnace desulfurization in the oxy-fuel combustion system, they were injected into high temperature drop tube furnace (DTF). Experiments were conducted at varying temperatures, residence times, and atmospheric conditions in a reactor. To evaluate the aerosolizing characteristics of the CaCO{sub 3} sorbent particle, changes in the size distribution and total particle concentration between the DTF inlet and outlet were measured. Structural changes (e.g., porosity, grain size, and morphology) of the calcined sorbent particles were estimated by BET/BJH, XRD, and SEM analyses. It was shown that sorbent particles rapidly calcined and sintered in the air atmosphere, whereas calcination was delayed in the CO{sub 2} atmosphere due to the higher CO{sub 2} partial pressure. Instead, the sintering effect was dominant in the CO{sub 2} atmosphere early in the reaction. Based on the SEM images, it was shown that the reactions of sorbent particles could be explained as a grain-subgrain structure model in both the air and CO{sub 2} atmospheres.

  15. Preparation of calcium carbonate particles coated with titanium dioxide

    Institute of Scientific and Technical Information of China (English)

    Hai Lin; Ying-bo Dong; Le-yong Jiang

    2009-01-01

    The preparation of a new mineral composite material, calcium carbonate particles coated with titanium dioxide, was stud-ied. The mechanism of the preparation process was proposed. The new mineral composite material was made by the mechanochemi-eal method under the optimum condition that the mass ratio of calcium carbonate particles to titanium dioxide was 6.5:3.5. The mass ratios of two different types of titanium dioxide (anatase to rutile) and grinding media to grinded materials were 8:2 and 4:1 respec-tively, and the modified density was 60%. Under this condition, the new material was capable of forming after 120-min modification.The hiding power and oil absorption of this new material were 29.12 g/m~2 and 23.30%, respectively. The results show that the modi-fication is based on surface hydroxylation. After coating with titanium dioxide, the hiding power of calcium carbonate can be im-proved greatly. The new mineral composite materials can be used as the substitute for titanium dioxide.

  16. Innershell ionization by fast protons, alpha particles and carbon ions

    International Nuclear Information System (INIS)

    The subject of this thesis is the study of inner-shell excitations of atoms induced by fast charged particle collisions. A new method is described for measuring the spectrum of delta-electrons emitted by 208Pb after excitation by 15 MeV protons or 50 MeV alpha particles. Experimental equipment is described. Results of both experiments are presented and compared with PWBA models and with calculations based on a semi-classical approximation. The small-impact-parameter ionization probabilities obtained are then compared with literature. Also small-impact-parameter measurements done with 100 MeV carbon ions are described. Besides K-shell measurements, the author also presents L-subshell ionization probability results for Pb. An appendix is added in which energy straggling problems in solid targets are treated. (Auth./G.J.P.)

  17. Characterization of diesel particles: effects of fuel reformulation, exhaust aftertreatment, and engine operation on particle carbon composition and volatility.

    Science.gov (United States)

    Alander, Timo J A; Leskinen, Ari P; Raunemaa, Taisto M; Rantanen, Leena

    2004-05-01

    Diesel exhaust particles are the major constituent of urban carbonaceous aerosol being linked to a large range of adverse environmental and health effects. In this work, the effects of fuel reformulation, oxidation catalyst, engine type, and engine operation parameters on diesel particle emission characteristics were investigated. Particle emissions from an indirect injection (IDI) and a direct injection (DI) engine car operating under steady-state conditions with a reformulated low-sulfur, low-aromatic fuel and a standard-grade fuel were analyzed. Organic (OC) and elemental (EC) carbon fractions of the particles were quantified by a thermal-optical transmission analysis method and particle size distributions measured with a scanning mobility particle sizer (SMPS). The particle volatility characteristics were studied with a configuration that consisted of a thermal desorption unit and an SMPS. In addition, the volatility of size-selected particles was determined with a tandem differential mobility analyzer technique. The reformulated fuel was found to produce 10-40% less particulate carbon mass compared to the standard fuel. On the basis of the carbon analysis, the organic carbon contributed 27-61% to the carbon mass of the IDI engine particle emissions, depending on the fuel and engine operation parameters. The fuel reformulation reduced the particulate organic carbon emissions by 10-55%. In the particles of the DI engine, the organic carbon contributed 14-26% to the total carbon emissions, the advanced engine technology, and the oxidation catalyst, thus reducing the OC/EC ratio of particles considerably. A relatively good consistency between the particulate organic fraction quantified with the thermal optical method and the volatile fraction measured with the thermal desorption unit and SMPS was found.

  18. Resistin does not down-regulate the transcription of insulin receptor promoter

    Institute of Scientific and Technical Information of China (English)

    Xiao-zhi QIAO; Xian-feng WANG; Zhe-rong XU; Yun-mei YANG

    2008-01-01

    Objective: To detect the effect of resistin on the transcription of insulin receptor promoter. Methods: Luciferase reporter gene was fused downstream of human insulin receptor promoter and the enzymatic activity of luciferase was determined in the presence or absence of resistin. The resistin expressed with plasmid was stained with antibody against Myc tag which was in frame fused with resistin coding sequence, and then imaged with confocal microscopy. Results: The treatment of pIRP-LUC transfected cells with recombinant resistin did not result in significant difference in the enzymatic activity of luciferase compared to the untreated cells. Cell staining showed that green fluorescence could be observed in the cytoplasm, but not in the nucleus. Conclusion: The results suggest that the endogenous resistin may functionally locate in the cytoplasm, but does not enter the nucleus and not down-regulate the transcription of insulin receptor promoter.

  19. Expression of NDRG2 is down-regulated in high-risk adenomas and colorectal carcinoma

    DEFF Research Database (Denmark)

    Lorentzen, Anders; Vogel, Lotte K.; Lewinsky, Rikke H;

    2007-01-01

    examine NDRG2 mRNA expression in colon cancer. By examining affected and normal tissue from individuals with colorectal adenomas and carcinomas, as well as in healthy individuals, we aim to determine whether and at which stages NDRG2 down-regulation occurs during colonic carcinogenesis. METHODS: Using...... quantitative RT-PCR, we have determined the mRNA levels for NDRG2 in low-risk (n = 15) and high-risk adenomas (n = 57), colorectal carcinomas (n = 50) and corresponding normal tissue, as well as control tissue from healthy individuals (n = 15). NDRG2 levels were normalised to beta-actin. RESULTS: NDRG2 m......RNA levels were lower in colorectal carcinomas compared to normal tissue from the control group (p < 0.001). When comparing adenomas/carcinomas with adjacent normal tissue from the same individual, NDRG2 expression levels were significantly reduced in both high-risk adenoma (p < 0.001) and in colorectal...

  20. Down regulation of hepatic PPARalpha function by AhR ligand.

    Science.gov (United States)

    Shaban, Zein; El-Shazly, Samir; Abdelhady, Shawky; Fattouh, Ibrahim; Muzandu, Kaampwe; Ishizuka, Mayumi; Kimura, Kazuhiro; Kazusaka, Akio; Fujita, Shoichi

    2004-11-01

    Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that mediates a spectrum of toxic and biological effects of 2,3,7,8-tetrachloro dibenzo-p-dioxin (TCDD) and related compounds. Peroxisome proliferator activated receptor alpha (PPARalpha) is a nuclear receptor involved in the maintenance of lipid and glucose homeostasis. In this study we hypothesized that one of the possible mechanisms for the effect of TCDD and its related chemicals on fat metabolism could be through down regulation of PPARalpha functions. We treated Wistar rats with an AhR ligand, Sudan III (S.III), and/or PPARalpha ligand, Clofibric Acid (CA), for 3 days. We analysed the expression of one of the PPARalpha-target gene products, CYP4A protein and its mRNA. We also tested HepG2 cells with the afore-mentioned treatments and evaluated their effects on PPARalpha and RXRalpha protein. Treatment of Wistar rats with S.III was found to down regulates CYP4A protein expression and reduced its induction with CA. It also decreased mRNA expressions of CYP4A1, CYP4A2, CYP4A3 and PPARalpha. In HepG2 cells, PPARalpha and RXRalpha protein expression was decreased by S.III treatment in a dose dependent manner. Our results suggest that AhR has an inhibitory effect on PPARalpha function and a new pathway by which AhR ligands could disturb lipid metabolism. PMID:15585952

  1. Hydrogen peroxide down-regulates inositol 1,4,5-trisphosphate receptor content through proteasome activation.

    Science.gov (United States)

    Martín-Garrido, A; Boyano-Adánez, M C; Alique, M; Calleros, L; Serrano, I; Griera, M; Rodríguez-Puyol, D; Griendling, K K; Rodríguez-Puyol, M

    2009-11-15

    Hydrogen peroxide (H(2)O(2)) is implicated in the regulation of signaling pathways leading to changes in vascular smooth muscle function. Contractile effects produced by H(2)O(2) are due to the phosphorylation of myosin light chain kinase triggered by increases in intracellular calcium (Ca(2+)) from intracellular stores or influx of extracellular Ca(2+). One mechanism for mobilizing such stores involves the phosphoinositide pathway. Inositol 1,4,5-trisphosphate (IP(3)) mobilizes intracellular Ca(2+) by binding to a family of receptors (IP(3)Rs) on the endoplasmic-sarcoplasmic reticulum that act as ligand-gated Ca(2+) channels. IP(3)Rs can be rapidly ubiquitinated and degraded by the proteasome, causing a decrease in cellular IP(3)R content. In this study we show that IP(3)R(1) and IP(3)R(3) are down-regulated when vascular smooth muscle cells (VSMC) are stimulated by H(2)O(2), through an increase in proteasome activity. Moreover, we demonstrate that the decrease in IP(3)R by H(2)O(2) is accompanied by a reduction in calcium efflux induced by IP(3) in VSMC. Also, we observed that angiotensin II (ANGII) induces a decrease in IP(3)R by activation of NADPH oxidase and that preincubation with H(2)O(2) decreases ANGII-mediated calcium efflux and planar cell surface area in VSMC. The decreased IP(3) receptor content observed in cells was also found in aortic rings, which exhibited a decreased ANGII-dependent contraction after treatment with H(2)O(2). Altogether, these results suggest that H(2)O(2) mediates IP(3)R down-regulation via proteasome activity.

  2. Steatogenesis in adult-onset type II citrullinemia is associated with down-regulation of PPARα.

    Science.gov (United States)

    Komatsu, Michiharu; Kimura, Takefumi; Yazaki, Masahide; Tanaka, Naoki; Yang, Yang; Nakajima, Takero; Horiuchi, Akira; Fang, Zhong-Ze; Joshita, Satoru; Matsumoto, Akihiro; Umemura, Takeji; Tanaka, Eiji; Gonzalez, Frank J; Ikeda, Shu-Ichi; Aoyama, Toshifumi

    2015-03-01

    SLC25A13 (citrin or aspartate-glutamate carrier 2) is located in the mitochondrial membrane in the liver and its genetic deficiency causes adult-onset type II citrullinemia (CTLN2). CTLN2 is one of the urea cycle disorders characterized by sudden-onset hyperammonemia due to reduced argininosuccinate synthase activity. This disorder is frequently accompanied with hepatosteatosis in the absence of obesity and ethanol consumption. However, the precise mechanism of steatogenesis remains unclear. The expression of genes associated with fatty acid (FA) and triglyceride (TG) metabolism was examined using liver samples obtained from 16 CTLN2 patients and compared with 7 healthy individuals. Although expression of hepatic genes associated with lipogenesis and TG hydrolysis was not changed, the mRNAs encoding enzymes/proteins involved in FA oxidation (carnitine palmitoyl-CoA transferase 1α, medium- and very-long-chain acyl-CoA dehydrogenases, and acyl-CoA oxidase 1), very-low-density lipoprotein secretion (microsomal TG transfer protein), and FA transport (CD36 and FA-binding protein 1), were markedly suppressed in CTLN2 patients. Serum concentrations of ketone bodies were also decreased in these patients, suggesting reduced mitochondrial β-oxidation activity. Consistent with these findings, the expression of peroxisome proliferator-activated receptor α (PPARα), a master regulator of hepatic lipid metabolism, was significantly down-regulated. Hepatic PPARα expression was inversely correlated with severity of steatosis and circulating ammonia and citrulline levels. Additionally, phosphorylation of c-Jun-N-terminal kinase was enhanced in CTLN2 livers, which was likely associated with lower hepatic PPARα. Collectively, down-regulation of PPARα is associated with steatogenesis in CTLN2 patients. These findings provide a novel link between urea cycle disorder, lipid metabolism, and PPARα.

  3. BMP4 and LGL1 are Down Regulated in an Ovine Model of Congenital Diaphragmatic Hernia

    Directory of Open Access Journals (Sweden)

    Heather eEmmerton-Coughlin

    2014-11-01

    Full Text Available Background/Purpose: The molecular pathophysiology of lung hypoplasia in congenital diaphragmatic hernia (CDH remains poorly understood. The Wnt signaling pathway and downstream targets, such as bone morphogenetic proteins (BMP 4 and other factors such as late gestation lung protein 1 (LGL1, are essential to normal lung development. Nitrofen-induced hypoplastic CDH rodent lungs demonstrate down regulation of the Wnt pathway including BMP4 and reduced LGL1 expression. The aim of the current study was to examine the molecular pathophysiology associated with a surgically induced CDH in an ovine model. Methods: Left thoracotomy was performed at 80 days in 14 fetal sheep; CDH was created in 7 experimental animals. Lungs were harvested at 136 days (term=145d. Lung weight and mean terminal bronchiole density (MTBD were measured to determine the degree of pulmonary hypoplasia. Quantitative real time PCR was undertaken to analyze Wnt2, Wnt7b, BMP4 and LGL1 mRNA expression. Results: Total lung weight was decreased while MTBD was increased in the CDH group (p<0.05, confirming pulmonary hypoplasia. BMP4 and LGL1 mRNA was significantly reduced in CDH lungs (p<0.05. Wnt2 mRNA was decreased, although not significantly (p<0.06. Conclusions: For the first time, down regulation of BMP4 and Lgl1 are reported in an ovine CDH model. In contrast to other animal models, these changes are persistent to near term. These findings suggest that mechanical compression from herniated viscera may play a more important role in causing pulmonary hypoplasia in CDH, rather than a primary defect in lung organogenesis.

  4. Ezrin mediates neuritogenesis via down-regulation of RhoA activity in cultured cortical neurons.

    Directory of Open Access Journals (Sweden)

    Yosuke Matsumoto

    Full Text Available Neuronal morphogenesis is implicated in neuronal function and development with rearrangement of cytoskeletal organization. Ezrin, a member of Ezrin/Radixin/Moesin (ERM proteins links between membrane proteins and actin cytoskeleton, and contributes to maintenance of cellular function and morphology. In cultured hippocampal neurons, suppression of both radixin and moesin showed deficits in growth cone morphology and neurite extensions. Down-regulation of ezrin using siRNA caused impairment of netrin-1-induced axon outgrowth in cultured cortical neurons. However, roles of ezrin in the neuronal morphogenesis of the cultured neurons have been poorly understood. In this report, we performed detailed studies on the roles of ezrin in the cultured cortical neurons prepared from the ezrin knockdown (Vil2(kd/kd mice embryo that showed a very small amount of ezrin expression compared with the wild-type (Vil2(+/+ neurons. Ezrin was mainly expressed in cell body in the cultured cortical neurons. We demonstrated that the cultured cortical neurons prepared from the Vil2(kd/kd mice embryo exhibited impairment of neuritogenesis. Moreover, we observed increased RhoA activity and phosphorylation of myosin light chain 2 (MLC2, as a downstream effector of RhoA in the Vil2(kd/kd neurons. In addition, inhibition of Rho kinase and myosin II rescued the impairment of neuritogenesis in the Vil2(kd/kd neurons. These data altogether suggest a novel role of ezrin in the neuritogenesis of the cultured cortical neurons through down-regulation of RhoA activity.

  5. PPARα activators down-regulate CYP2C7, a retinoic acid and testosterone hydroxylase

    International Nuclear Information System (INIS)

    Peroxisome proliferators (PP) are a large class of structurally diverse chemicals that mediate their effects in the liver mainly through the peroxisome proliferator-activated receptor α (PPARα). Exposure to PP results in down-regulation of CYP2C family members under control of growth hormone and sex steroids including CYP2C11 and CYP2C12. We hypothesized that PP exposure would also lead to similar changes in CYP2C7, a retinoic acid and testosterone hydroxylase. CYP2C7 gene expression was dramatically down-regulated in the livers of rats treated for 13 weeks by WY-14,643 (WY; 500 ppm) or gemfibrozil (GEM; 8000 ppm). In the same tissues, exposure to WY and GEM and to a lesser extent di-n-butyl phthalate (20 000 ppm) led to decreases in CYP2C7 protein levels in both male and female rats. An examination of the time and dose dependence of CYP2C7 protein changes after PP exposure revealed that CYP2C7 was more sensitive to compound exposure compared to other CYP2C family members. Protein expression was decreased after 1, 5 and 13 weeks of PP treatment. CYP2C7 protein expression was completely abolished at 5 ppm WY, the lowest dose tested. GEM and DBP exhibited dose-dependent decreases in CYP2C7 protein expression, becoming significant at 1000 ppm or 5000 ppm and above, respectively. These results show that PP exposure leads to changes in CYP2C7 mRNA and protein levels. Thus, in addition to known effects on steroid metabolism, exposure to PP may alter retinoic acid metabolism

  6. Microbial symbionts in insects influence down-regulation of defense genes in maize.

    Directory of Open Access Journals (Sweden)

    Kelli L Barr

    Full Text Available Diabrotica virgifera virgifera larvae are root-feeding insects and significant pests to maize in North America and Europe. Little is known regarding how plants respond to insect attack of roots, thus complicating the selection for plant defense targets. Diabrotica virgifera virgifera is the most successful species in its genus and is the only Diabrotica beetle harboring an almost species-wide Wolbachia infection. Diabrotica virgifera virgifera are infected with Wolbachia and the typical gut flora found in soil-living, phytophagous insects. Diabrotica virgifera virgifera larvae cannot be reared aseptically and thus, it is not possible to observe the response of maize to effects of insect gut flora or other transient microbes. Because Wolbachia are heritable, it is possible to investigate whether Wolbachia infection affects the regulation of maize defenses. To answer if the success of Diabrotica virgifera virgifera is the result of microbial infection, Diabrotica virgifera virgifera were treated with antibiotics to eliminate Wolbachia and a microarray experiment was performed. Direct comparisons made between the response of maize root tissue to the feeding of antibiotic treated and untreated Diabrotica virgifera virgifera show down-regulation of plant defenses in the untreated insects compared to the antibiotic treated and control treatments. Results were confirmed via QRT-PCR. Biological and behavioral assays indicate that microbes have integrated into Diabrotica virgifera virgifera physiology without inducing negative effects and that antibiotic treatment did not affect the behavior or biology of the insect. The expression data and suggest that the pressure of microbes, which are most likely Wolbachia, mediate the down-regulation of many maize defenses via their insect hosts. This is the first report of a potential link between a microbial symbiont of an insect and a silencing effect in the insect host plant. This is also the first expression

  7. Capsaicin inhibits the Wnt/β-catenin signaling pathway by down-regulating PP2A.

    Science.gov (United States)

    Park, Dong-Seok; Yoon, Gang-Ho; Lee, Hyun-Shik; Choi, Sun-Cheol

    2016-09-01

    Xenopus embryo serves as an ideal model for teratogenesis assays to examine the effects of any substances on the cellular processes critical for early development and adult tissue homeostasis. In our chemical library screening with frog embryo, capsaicin was found to repress the Wnt/β-catenin signaling. Depending on the stages at which embryos became exposed to capsaicin, it could disrupt formation of dorsal or posterior body axis of embryo, which is associated with inhibition of maternal or zygotic Wnt signal in early development. In agreement with these phenotypes, capsaicin suppressed the expression of Wnt target genes such as Siamois and Chordin in the organizer region of embryo and in Wnt signals-stimulated tissue explants. In addition, the cellular level of β-catenin, a key component of Wnt pathway, was down-regulated in capsaicin-treated embryonic cells. Unlike wild-type β-catenin, its non-phosphorylatable mutant in which serine and threonine residues phosphorylated by GSK3 are substituted with alanine was not destabilized by capsaicin, indicative of the effect of this chemical on the phosphorylation status of β-catenin. In support of this, capsaicin up-regulated the level of GSK3- or CK1-phosphorylated β-catenin, concomitantly lowering that of its de-phosphorylated version. Notably, capsaicin augmented the phosphorylation of a phosphatase, PP2A at tyrosine 307, suggesting its repression of the enzymatic activity of the phosphatase. Furthermore, capsaicin still enhanced β-catenin phosphorylation in cells treated with a GSK3 inhibitor, LiCl but not in those treated with a phosphatase inhibitor, okadaic acid. Together, these results indicate that capsaicin inhibits the patterning of the dorso-ventral and anterior-posterior body axes of embryo by repressing PP2A and thereby down-regulating the Wnt/β-catenin signaling. PMID:27318088

  8. Steatogenesis in adult-onset type II citrullinemia is associated with down-regulation of PPARα.

    Science.gov (United States)

    Komatsu, Michiharu; Kimura, Takefumi; Yazaki, Masahide; Tanaka, Naoki; Yang, Yang; Nakajima, Takero; Horiuchi, Akira; Fang, Zhong-Ze; Joshita, Satoru; Matsumoto, Akihiro; Umemura, Takeji; Tanaka, Eiji; Gonzalez, Frank J; Ikeda, Shu-Ichi; Aoyama, Toshifumi

    2015-03-01

    SLC25A13 (citrin or aspartate-glutamate carrier 2) is located in the mitochondrial membrane in the liver and its genetic deficiency causes adult-onset type II citrullinemia (CTLN2). CTLN2 is one of the urea cycle disorders characterized by sudden-onset hyperammonemia due to reduced argininosuccinate synthase activity. This disorder is frequently accompanied with hepatosteatosis in the absence of obesity and ethanol consumption. However, the precise mechanism of steatogenesis remains unclear. The expression of genes associated with fatty acid (FA) and triglyceride (TG) metabolism was examined using liver samples obtained from 16 CTLN2 patients and compared with 7 healthy individuals. Although expression of hepatic genes associated with lipogenesis and TG hydrolysis was not changed, the mRNAs encoding enzymes/proteins involved in FA oxidation (carnitine palmitoyl-CoA transferase 1α, medium- and very-long-chain acyl-CoA dehydrogenases, and acyl-CoA oxidase 1), very-low-density lipoprotein secretion (microsomal TG transfer protein), and FA transport (CD36 and FA-binding protein 1), were markedly suppressed in CTLN2 patients. Serum concentrations of ketone bodies were also decreased in these patients, suggesting reduced mitochondrial β-oxidation activity. Consistent with these findings, the expression of peroxisome proliferator-activated receptor α (PPARα), a master regulator of hepatic lipid metabolism, was significantly down-regulated. Hepatic PPARα expression was inversely correlated with severity of steatosis and circulating ammonia and citrulline levels. Additionally, phosphorylation of c-Jun-N-terminal kinase was enhanced in CTLN2 livers, which was likely associated with lower hepatic PPARα. Collectively, down-regulation of PPARα is associated with steatogenesis in CTLN2 patients. These findings provide a novel link between urea cycle disorder, lipid metabolism, and PPARα. PMID:25533124

  9. A review: Different methods producing different particles size and distribution in synthesis of calcium carbonate nano particles

    Science.gov (United States)

    Sulimai, N. H.; Rusop, M.; Alrokayan, Salman A. H.; Khan, Haseeb A.

    2016-07-01

    Carbonates exist as 73 percent of world crust carbon. Abundance and bioavailability of Calcium Carbonates offer reliable resources, costs saving and environmental friendly potentials in its applications. Studies proven nano-sized Calcium Cabonate (nCC) employs a more significant characteristics compared to larger sizes. Properties of nCC is affected by the dispersion of the particles in which agglomeration occurs. It is important to gain more understanding of the conditions contributing or stunting the agglomeration to gain more control of the particles morphology and dynamic. A few recent studies with different methods to prepare calcium carbonate nanoparticles were listed in Table 1 .Particle size and dispersity of calcium carbonate are affected by different conditions of its preparation. Other factors such as mechanical aggression, concentration of solution, temperature of precipitation, pH of reaction are all contributing factors towards particle sizes and distribution.

  10. Control on Crystal Forms of Ultrafine Barium Carbonate Particles and Study on its Mechanism

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    Barium carbonate particles were prepared by using homogeneous precipitation method and co-precipitation method respectively. Through adding different crystalline controlling modifiers, Barium carbonate particles in five different shapes including linear, needle-like, pillarlike, sphere-like and dumbbell-like were synthesized. These particles were characterized by SEM and XRD, and their synthetic mechanism was discussed in this paper.

  11. Dynamics of formation of particles of the condensed carbon phase at shock compression of organic materials

    CERN Document Server

    Fedotov, M G; Luckjanchikov, L A; Lyakhov, N Z; Sharafutdinov, M R; Sheromov, M A; Ten, K A; Titov, V M; Tolochko, B P; Zubkov, P I

    2001-01-01

    Results of the SR study of the density behavior and dynamics of formation of condensed carbon particles at expansion of shock waves in organic materials and some low-sensitive explosives as well as at shock loading of ultra-dispersed diamonds are presented. Appearance of particles of the condensed carbon phase was observed in carbon-rich organic materials.

  12. Protein kinase C (PKC) alpha and PKC theta are the major PKC isotypes involved in TCR down-regulation

    DEFF Research Database (Denmark)

    von Essen, Marina; Nielsen, Martin W; Bonefeld, Charlotte M;

    2006-01-01

    study was to identify the PKC isotype(s) involved in TCR down-regulation and to elucidate the mechanism by which they induce TCR down-regulation. To accomplish this, we studied TCR down-regulation in the human T cell line Jurkat, in primary human T cells, or in the mouse T cell line DO11.10 in which we......It is well known that protein kinase C (PKC) plays an important role in regulation of TCR cell surface expression levels. However, eight different PKC isotypes are present in T cells, and to date the particular isotype(s) involved in TCR down-regulation remains to be identified. The aim of this...... either overexpressed constitutive active or dominant-negative forms of various PKC isotypes. In addition, we studied TCR down-regulation in PKC knockout mice and by using small interfering RNA-mediated knockdown of specific PKC isotypes. We found that PKCalpha and PKCtheta were the only PKC isotypes able...

  13. Unambiguous evidence of old soil carbon in grass biosilica particles

    Science.gov (United States)

    Reyerson, Paul E.; Alexandre, Anne; Harutyunyan, Araks; Corbineau, Remi; Martinez De La Torre, Hector A.; Badeck, Franz; Cattivelli, Luigi; Santos, Guaciara M.

    2016-03-01

    Plant biosilica particles (phytoliths) contain small amounts of carbon called phytC. Based on the assumptions that phytC is of photosynthetic origin and a closed system, claims were recently made that phytoliths from several agriculturally important monocotyledonous species play a significant role in atmospheric CO2 sequestration. However, anomalous phytC radiocarbon (14C) dates suggested contributions from a non-photosynthetic source to phytC. Here we address this non-photosynthetic source hypothesis using comparative isotopic measurements (14C and δ13C) of phytC, plant tissues, atmospheric CO2, and soil organic matter. State-of-the-art methods assured phytolith purity, while sequential stepwise-combustion revealed complex chemical-thermal decomposability properties of phytC. Although photosynthesis is the main source of carbon in plant tissue, it was found that phytC is partially derived from soil carbon that can be several thousand years old. The fact that phytC is not uniquely constituted of photosynthetic C limits the usefulness of phytC either as a dating tool or as a significant sink of atmospheric CO2. It additionally calls for further experiments to investigate how SOM-derived C is accessible to roots and accumulates in plant biosilica, for a better understanding of the mechanistic processes underlying the silicon biomineralization process in higher plants.

  14. Genetically Determined Insulin Resistance is Characterized by Down-Regulation of Mitochondrial Oxidative Metabolism in Human Skeletal Muscle

    DEFF Research Database (Denmark)

    Kristensen, Jonas M; Skov, Vibe; Wojtaszewski, Jørgen;

    2010-01-01

    mitochondrial dysfunction is a cause or consequence of insulin resistance remains to be clarified. In the present study, we tested the hypothesis that mitochondrial oxidative metabolism was down-regulated in skeletal muscle of patients with genetically determined insulin resistance. Skeletal muscle biopsies......Transcriptional profiling of skeletal muscle from patients with type 2 diabetes and high-risk individuals have demonstrated a co-ordinated down-regulation of oxidative phosphorylation (OxPhos) genes, suggesting a link between insulin resistance and mitochondrial dysfunction. However, whether.......02), and complex V (ATP5B; p=0.005). Our data demonstrate that genetically determined insulin resistance is associated with a co-ordinated down-regulation of OxPhos components both at the transcriptional and translational level. These findings suggest that an impaired biological response to insulin in skeletal...

  15. miR-191 regulates mouse erythroblast enucleation by down-regulating Riok3 and Mxi1.

    Science.gov (United States)

    Zhang, Lingbo; Flygare, Johan; Wong, Piu; Lim, Bing; Lodish, Harvey F

    2011-01-15

    Using RNA-seq technology, we found that the majority of microRNAs (miRNAs) present in CFU-E erythroid progenitors are down-regulated during terminal erythroid differentiation. Of the developmentally down-regulated miRNAs, ectopic overexpression of miR-191 blocks erythroid enucleation but has minor effects on proliferation and differentiation. We identified two erythroid-enriched and developmentally up-regulated genes, Riok3 and Mxi1, as direct targets of miR-191. Knockdown of either Riok3 or Mxi1 blocks enucleation, and either physiological overexpression of miR-191 or knockdown of Riok3 or Mxi1 blocks chromatin condensation. Thus, down-regulation of miR-191 is essential for erythroid chromatin condensation and enucleation by allowing up-regulation of Riok3 and Mxi1.

  16. Protein Kinase C-δ mediates down-regulation of heterogeneous nuclear ribonucleoprotein K protein: involvement in apoptosis induction

    International Nuclear Information System (INIS)

    We reported previously that NSC606985, a camptothecin analogue, induces apoptosis of acute myeloid leukemia (AML) cells through proteolytic activation of protein kinase C delta (ΔPKC-δ). By subcellular proteome analysis, heterogeneous nuclear ribonucleoprotein K (hnRNP K) was identified as being significantly down-regulated in NSC606985-treated leukemic NB4 cells. HnRNP K, a docking protein for DNA, RNA, and transcriptional or translational molecules, is implicated in a host of processes involving the regulation of gene expression. However, the molecular mechanisms of hnRNP K reduction and its roles during apoptosis are still not understood. In the present study, we found that, following the appearance of the ΔPKC-δ, hnRNP K protein was significantly down-regulated in NSC606985, doxorubicin, arsenic trioxide and ultraviolet-induced apoptosis. We further provided evidence that ΔPKC-δ mediated the down-regulation of hnRNP K protein during apoptosis: PKC-δ inhibitor could rescue the reduction of hnRNP K; hnRNP K failed to be decreased in PKC-δ-deficient apoptotic KG1a cells; conditional induction of ΔPKC-δ in U937T cells directly down-regulated hnRNP K protein. Moreover, the proteasome inhibitor also inhibited the down-regulation of hnRNP K protein by apoptosis inducer and the conditional expression of ΔPKC-δ. More intriguingly, the suppression of hnRNP K with siRNA transfection significantly induced apoptosis. To our knowledge, this is the first demonstration that proteolytically activated PKC-δ down-regulates hnRNP K protein in a proteasome-dependent manner, which plays an important role in apoptosis induction.

  17. Catalytic Metal Free Production of Large Cage Structure Carbon Particles: A Candidate for Hydrogen Storage

    Science.gov (United States)

    Kimura, Yuki; Nuth, Joseph A., III; Ferguson, Frank T.

    2005-01-01

    We will demonstrate that carbon particles consisting of large cages can be produced without catalytic metal. The carbon particles were produced in CO gas as well as by introduction of 5% methane gas into the CO gas. The gas-produced carbon particles were able to absorb approximately 16.2 wt% of hydrogen. This value is 2.5 times higher than the 6.5 wt% goal for the vehicular hydrogen storage proposed by the Department of Energy in the USA. Therefore, we believe that this carbon particle is an excellent candidate for hydrogen storage for fuel cells.

  18. SCFHOS ubiquitin ligase mediates the ligand-induced down-regulation of the interferon-α receptor

    OpenAIRE

    Suresh Kumar, K.G.; Tang, Weigang; Ravindranath, Abhilash K.; Clark, William A.; Croze, Ed; Fuchs, Serge Y.

    2003-01-01

    Down-regulation of activated signaling receptors in response to their ligands plays a key role in restricting the extent and duration of the signaling. Mechanisms underlying down-regulation of the type I interferon receptor consisting of IFNAR1 and IFNAR2 subunits remain largely unknown. Here we show that IFNAR1 interacts with the Homolog of Slimb (HOS) F-box protein in a phosphorylation-dependent manner, and that this interaction is promoted by interferon α (IFNα). IFNAR1 is ubiquitinated by...

  19. 垂体降调节方案的比较%Comparison between different pituitary down-regulation protocols

    Institute of Scientific and Technical Information of China (English)

    黄孙兴; 周灿权

    2012-01-01

    Pituitary down-regulation plays an important role in the development of assisted reproductive technology. It significantly improves the outcome of in vitro fertilization (IVF) and promotes relevant basic research in reproductive physiology. Since the emergence of this technique, many studies have been done to investigate the clinic effect of the different protocols. It took more than 20 years to identify some optimal protocols with the GnRH analogues in IVF, including long protocol, short protocol and GnRH antagonist protocol. Comparison of the difference among these classic protocols can provide theoretical basis for establishing the individual down-regulation protocol, as well as relevant clinical experience.

  20. Role of calcium signaling in down-regulation of aggrecan induced by cyclic tensile strain in annulus fibrosus cells

    Institute of Scientific and Technical Information of China (English)

    GUO Zhi-liang; ZHOU Yue; LI Hua-zhuang; CAO Guo-yong; TENG Hai-jun

    2006-01-01

    Objective:To study the role of intracellular calcium signal pathway in the down-regulation of aggrecan induced by cyclic tensile strain in the annulus fibrosus cells. Methods :The expression of aggrecan mRNA and core protein were respectively detected with RT-PCR and western blot after the channels transmitting calcium ions were blocked with EGTA, gadolinium and verapamil. Results:EGTA, gadolinium and verapamil partially prevented the effects of cyclic tensile strain on the expression of aggrecan in annulus fibrosus cells. Conclusion:The calcium signaling is involved in the down-regulation of proteoglycan resulting from cyclic tensile strain in the annulus fibrosus cells.

  1. Determining organic carbon distributions in soil particle size fractions as a precondition of lateral carbon transport modeling at large scales

    Science.gov (United States)

    Schindewolf, Marcus; Seher, Wiebke; Pfeffer, Eduard; Schultze, Nico; Amorim, Ricardo S. S.; Schmidt, Jürgen

    2016-04-01

    The erosional transport of organic carbon has an effect on the global carbon budget, however, it is uncertain, whether erosion is a sink or a source for carbon in the atmosphere. Continuous erosion leads to a massive loss of top soils including the loss of organic carbon historically accumulated in the soil humus fraction. The colluvial organic carbon could be protected from further degradation depending on the depth of the colluvial cover and local decomposing conditions. Another part of eroded soils and organic carbon will enter surface water bodies and might be transported over long distances. The selective nature of soil erosion results in a preferential transport of fine particles while less carbonic larger particles remain on site. Consequently organic carbon is enriched in the eroded sediment compared to the origin soil. As a precondition of process based lateral carbon flux modeling, carbon distribution on soil particle size fractions has to be known. In this regard the present study refers to the determination of organic carbon contents on soil particle size separates by a combined sieve-sedimentation method for different tropical and temperate soils Our results suggest high influences of parent material and climatic conditions on carbon distribution on soil particle separates. By applying these results in erosion modeling a test slope was simulated with the EROSION 2D simulation software covering certain land use and soil management scenarios referring to different rainfall events. These simulations allow first insights on carbon loss and depletion on sediment delivery areas as well as carbon gains and enrichments on deposition areas on the landscape scale and could be used as a step forward in landscape scaled carbon redistribution modeling.

  2. Dioscin enhances methotrexate absorption by down-regulating MDR1 in vitro and in vivo

    International Nuclear Information System (INIS)

    The purpose of this study was to investigate the enhancing effect of dioscin on the absorption of methotrexate (MTX) and clarify the molecular mechanism involved in vivo and in vitro. Dioscin increased MTX chemosensitivity and transepithelial flux in the absorptive direction, significantly inhibiting multidrug resistance 1 (MDR1) mRNA and protein expression and MDR1 promoter and nuclear factor κ-B (NF-κB) activities in Caco-2 cells. Moreover, inhibitor κB-α (IκB-α) degradation was inhibited by dioscin. Dioscin enhanced the intracellular concentration of MTX by down-regulating MDR1 expression through a mechanism that involves NF-κB signaling pathway inhibition in Caco-2 cells. Dioscin strengthened MTX absorption by inhibiting MDR1 expression in rat intestine. In addition, even though MTX is absorbed into the enterocytes, there was no increase in toxicity observed, and that, in fact, decreased toxicity was seen. - Highlights: • Dioscin raised MTX concentration by inhibiting MDR1 in Caco-2 cells. • Dioscin suppresses MDR1 by inhibiting NF-κB signaling pathway in Caco-2 cells. • Dioscin can enhance MTX absorption via inhibiting MDR1 in vivo and in vitro. • Dioscin did not increase MTX-induced gastrointestinal mucosal toxicity

  3. Down-Regulation of NDUFB9 Promotes Breast Cancer Cell Proliferation, Metastasis by Mediating Mitochondrial Metabolism.

    Directory of Open Access Journals (Sweden)

    Liang-Dong Li

    Full Text Available Despite advances in basic and clinical research, metastasis remains the leading cause of death in breast cancer patients. Genetic abnormalities in mitochondria, including mutations affecting complex I and oxidative phosphorylation, are found in breast cancers and might facilitate metastasis. Genes encoding complex I components have significant breast cancer prognostic value. In this study, we used quantitative proteomic analyses to compare a highly metastatic cancer cell line and a parental breast cancer cell line; and observed that NDUFB9, an accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (complex I, was down-regulated in highly metastatic breast cancer cells. Furthermore, we demonstrated that loss of NDUFB9 promotes MDA-MB-231 cells proliferation, migration, and invasion because of elevated levels of mtROS, disturbance of the NAD+/NADH balance, and depletion of mtDNA. We also showed that, the Akt/mTOR/p70S6K signaling pathway and EMT might be involved in this mechanism. Thus, our findings contribute novel data to support the hypothesis that misregulation of mitochondrial complex I NADH dehydrogenase activity can profoundly enhance the aggressiveness of human breast cancer cells, suggesting that complex I deficiency is a potential and important biomarker for further basic research or clinical application.

  4. Prion pathogenesis is unaltered following down-regulation of SIGN-R1.

    Science.gov (United States)

    Bradford, Barry M; Brown, Karen L; Mabbott, Neil A

    2016-10-01

    Prion diseases are infectious neurodegenerative disorders characterised by accumulations of abnormal prion glycoprotein in affected tissues. Following peripheral exposure, many prion strains replicate upon follicular dendritic cells (FDC) in lymphoid tissues before infecting the brain. An intact splenic marginal zone is important for the efficient delivery of prions to FDC. The marginal zone contains a ring of specific intercellular adhesion molecule-3-grabbing non-integrin related 1 (SIGN-R1)-expressing macrophages. This lectin binds dextran and capsular pneumococcal polysaccharides, and also enhances the clearance of apoptotic cells via interactions with complement components. Since prions are acquired as complement-opsonized complexes we determined the role of SIGN-R1 in disease pathogenesis. We show that transient down-regulation of SIGN-R1 prior to intravenous prion exposure had no effect on the early accumulation of prions upon splenic FDC or their subsequent spread to the brain. Thus, SIGN-R1 expression by marginal zone macrophages is not rate-limiting for peripheral prion disease pathogenesis.

  5. CUEDC2 down-regulation is associated with tumor growth and poor prognosis in lung adenocarcinoma.

    Science.gov (United States)

    Sun, Longhua; Bai, Lihong; Lin, Gengpeng; Wang, Ran; Liu, Yangli; Cai, Jinghuang; Guo, Yubiao; Zhu, Zhiwen; Xie, Canmao

    2015-08-21

    CUE domain-containing 2 (CUEDC2) is a multi-functional protein, which regulates cell cycle, growth factor signaling and inflammation. We found that CUEDC2 was low in lung adenocarcinoma cell lines and lung adenocarcinoma tissues at both mRNA and protein levels. Low levels of CUEDC2 were correlated with a shorter survival time in patients with lung adenocarcinoma (p = 0.004). CUEDC2 expression was correlated with tumor T classification (P = 0.001) at clinical stage (P = 0.001) and tumor size (P = 0.033). Multivariate analysis suggested that CUEDC2 expression is an independent prognostic indicator for patients with lung adenocarcinoma. Ectopic expression of CUEDC2 decreased cell proliferation in vitro and inhibited tumor growth in nude mice in vivo. Knockdown of endogenous CUEDC2 by short hairpin RNAs (shRNAs) increased tumor growth. Inhibition of proliferation by CUEDC2 was associated with inactivation of the PI3K/Akt pathway, induction of p21 and down-regulation of cyclin D1. Our results suggest that decreased expression of CUEDC2 contributes to tumor growth in lung adenocarcinoma, leading to a poor clinical outcome.

  6. Selective down-regulation of nuclear poly(ADP-ribose glycohydrolase.

    Directory of Open Access Journals (Sweden)

    David M Burns

    Full Text Available BACKGROUND: The formation of ADP-ribose polymers on target proteins by poly(ADP-ribose polymerases serves a variety of cell signaling functions. In addition, extensive activation of poly(ADP-ribose polymerase-1 (PARP-1 is a dominant cause of cell death in ischemia-reperfusion, trauma, and other conditions. Poly(ADP-ribose glycohydrolase (PARG degrades the ADP-ribose polymers formed on acceptor proteins by PARP-1 and other PARP family members. PARG exists as multiple isoforms with differing subcellular localizations, but the functional significance of these isoforms is uncertain. METHODS / PRINCIPAL FINDINGS: Primary mouse astrocytes were treated with an antisense phosphorodiamidate morpholino oligonucleotide (PMO targeted to exon 1 of full-length PARG to suppress expression of this nuclear-specific PARG isoform. The antisense-treated cells showed down-regulation of both nuclear PARG immunoreactivity and nuclear PARG enzymatic activity, without significant alteration in cytoplasmic PARG activity. When treated with the genotoxic agent MNNG to induced PARP-1 activation, the antisense-treated cells showed a delayed rate of nuclear PAR degradation, reduced nuclear condensation, and reduced cell death. CONCLUSIONS/SIGNIFICANCE: These results support a preferentially nuclear localization for full-length PARG, and suggest a key role for this isoform in the PARP-1 cell death pathway.

  7. Chronic exposure to hexachlorobenzene results in down-regulation of connexin43 in the breast.

    Science.gov (United States)

    Delisle, Ariane; Ferraris, Emanuelle; Plante, Isabelle

    2015-11-01

    Decreased expression of connexins has been associated with cancer, but the underlying mechanisms are poorly understood. We have previously shown that a 5 day exposure to hexachlorobenzene (HCB) resulted in decreased connexins expression in hepatocytes 45 days later, and that this down-regulation was linked to activation of Akt through the ILK pathway. Because HCB promotes cancer in both the liver and breast, the present study aimed to determine if the mechanisms are similar in both tissues. MCF-12A breast cells were thus transfected with vectors coding for either Akt or a constitutively active form of Akt. In those cells, activation of Akt was correlated with decreased Cx43 levels. Female rats were then exposed to HCB by gavage either following the same protocol used previously for the liver or through a chronic exposure. While no changes were observed after the 5 days exposure protocol, chronic exposure to HCB resulted in increased Akt levels and decreased Cx43 levels in breast cells. In vitro, Akt was activated in MCF-12A cells exposed to HCB either for 7 days or chronically, but no changes were observed in junctional proteins. Together, these results suggested that, while activation of Akt can decrease Cx43 expression in breast cells in vitro, other mechanisms are involved during HCB exposure, leading to a decrease in Cx43 levels in a model- and duration-dependent manner. Finally, we showed that HCB effects are tissue specific, as we did not observe the same results in breast and liver tissues.

  8. Dioscin enhances methotrexate absorption by down-regulating MDR1 in vitro and in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Lijuan, E-mail: jlwang1979@163.com [Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian, Liaoning (China); Wang, Changyuan, E-mail: wangcyuan@163.com [Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian, Liaoning (China); Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning, Dalian Medical University, Dalian, Liaoning (China); Peng, Jinyong, E-mail: jinyongpeng2005@163.com [Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian, Liaoning (China); Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning, Dalian Medical University, Dalian, Liaoning (China); Liu, Qi, E-mail: llaqii@yahoo.com.cn [Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian, Liaoning (China); Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning, Dalian Medical University, Dalian, Liaoning (China); Meng, Qiang, E-mail: mengq531@yahoo.cn [Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian, Liaoning (China); Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning, Dalian Medical University, Dalian, Liaoning (China); Sun, Huijun, E-mail: sunhuijun@hotmail.com [Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian, Liaoning (China); Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning, Dalian Medical University, Dalian, Liaoning (China); Huo, Xiaokui, E-mail: huoxiaokui@163.com [Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian, Liaoning (China); Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning, Dalian Medical University, Dalian, Liaoning (China); and others

    2014-06-01

    The purpose of this study was to investigate the enhancing effect of dioscin on the absorption of methotrexate (MTX) and clarify the molecular mechanism involved in vivo and in vitro. Dioscin increased MTX chemosensitivity and transepithelial flux in the absorptive direction, significantly inhibiting multidrug resistance 1 (MDR1) mRNA and protein expression and MDR1 promoter and nuclear factor κ-B (NF-κB) activities in Caco-2 cells. Moreover, inhibitor κB-α (IκB-α) degradation was inhibited by dioscin. Dioscin enhanced the intracellular concentration of MTX by down-regulating MDR1 expression through a mechanism that involves NF-κB signaling pathway inhibition in Caco-2 cells. Dioscin strengthened MTX absorption by inhibiting MDR1 expression in rat intestine. In addition, even though MTX is absorbed into the enterocytes, there was no increase in toxicity observed, and that, in fact, decreased toxicity was seen. - Highlights: • Dioscin raised MTX concentration by inhibiting MDR1 in Caco-2 cells. • Dioscin suppresses MDR1 by inhibiting NF-κB signaling pathway in Caco-2 cells. • Dioscin can enhance MTX absorption via inhibiting MDR1 in vivo and in vitro. • Dioscin did not increase MTX-induced gastrointestinal mucosal toxicity.

  9. Down-Regulation of Bcl-2 Protein Sensitizes NCI 460 Cells to Radiotherapy-Induced Apoptosis

    Institute of Scientific and Technical Information of China (English)

    Dongmei He; Yuan Zhang; Gexiu Liu

    2006-01-01

    OBJECTIVE To determine whether Bcl-2 protein down-regulation can render NCI-460 cells more susceptible to gamma radiation-induced apoptosis by treatment with antisense oligonucleotide (ASODN) against the coding region of Bcl-2 mRNA.METHODS Cell survival was determined using the trypan blue dye exclusion. Expression of the Bcl-2 protein was assayed using immunofluorescence labeling with fluoresce isothiocyanate. Apoptosis was determined by Giemsa staining and flow cytomertry.RESULTS It was found that Bcl-2 ASODN combined with radiation significantly reduced the number of viable cells (P<0.05). There was no difference in cell survival between a nonsense oligodeoxynucleotide/radiation combination and cells treated with radiation alone. Bcl-2 ASODN combined with radiation significantly inhibited expression of the Bcl-2protein in the NCI-H460 cells (P<0.05). Using Giemsa staining, cells treated with Bcl-2 ASODN combined with radiation at 72 h displayed classic apoptotic changes. Apoptotic rates of the NCI-H460 cells treated with Bcl-2 ASODN combined with radiation significantly increased (P<0.05), compared with either a nonsense oligodeoxynucleotide/radiation combination or radiation-treatment cells alone.CONCLUSION ASODN against the coding region of Bcl-2 mRNA increases radiation-induced apoptosis in NCI-H460 cells.

  10. Carnosine reverses the aging-induced down regulation of brain regional serotonergic system.

    Science.gov (United States)

    Banerjee, Soumyabrata; Ghosh, Tushar K; Poddar, Mrinal K

    2015-12-01

    The purpose of the present investigation was to study the role of carnosine, an endogenous dipeptide biomolecule, on brain regional (cerebral cortex, hippocampus, hypothalamus and pons-medulla) serotonergic system during aging. Results showed an aging-induced brain region specific significant (a) increase in Trp (except cerebral cortex) and their 5-HIAA steady state level with an increase in their 5-HIAA accumulation and declination, (b) decrease in their both 5-HT steady state level and 5-HT accumulation (except cerebral cortex). A significant decrease in brain regional 5-HT/Trp ratio (except cerebral cortex) and increase in 5-HIAA/5-HT ratio were also observed during aging. Carnosine at lower dosages (0.5-1.0μg/Kg/day, i.t. for 21 consecutive days) didn't produce any significant response in any of the brain regions, but higher dosages (2.0-2.5μg/Kg/day, i.t. for 21 consecutive days) showed a significant response on those aging-induced brain regional serotonergic parameters. The treatment with carnosine (2.0μg/Kg/day, i.t. for 21 consecutive days), attenuated these brain regional aging-induced serotonergic parameters and restored towards their basal levels that observed in 4 months young control rats. These results suggest that carnosine attenuates and restores the aging-induced brain regional down regulation of serotonergic system towards that observed in young rats' brain regions. PMID:26364584

  11. Nutlin-3 down-regulates retinoblastoma protein expression and inhibits muscle cell differentiation

    International Nuclear Information System (INIS)

    The p53 tumor suppressor gene plays a critical role in regulation of proliferation, cell death and differentiation. The MDM2 oncoprotein is a major negative regulator for p53 by binding to and targeting p53 for proteasome-mediated degradation. The small molecule inhibitor, nutlin-3, disrupts MDM2-p53 interaction resulting in stabilization and activation of p53 protein. We have previously shown that nutlin-3 activates p53, leading to MDM2 accumulation as concomitant of reduced retinoblastoma (Rb) protein stability. It is well known that Rb is important in muscle development and myoblast differentiation and that rhabdomyosarcoma (RMS), or cancer of the skeletal muscle, typically harbors MDM2 amplification. In this study, we show that nutlin-3 inhibited myoblast proliferation and effectively prevented myoblast differentiation, as evidenced by lack of expression of muscle differentiation markers including myogenin and myosin heavy chain (MyHC), as well as a failure to form multinucleated myotubes, which were associated with dramatic increases in MDM2 expression and decrease in Rb protein levels. These results indicate that nutlin-3 can effectively inhibit muscle cell differentiation. - Highlights: • Nutlin-3 inhibits myoblast proliferation and prevents differentiation into myotubes. • Nutlin-3 increases MDM2 expression and down-regulates Rb protein levels. • This study has implication in nutlin-3 treatment of rhabdomyosarcomas

  12. Minocycline down-regulates topical mucosal inflammation during the application of microbicide candidates.

    Directory of Open Access Journals (Sweden)

    Liangzhu Li

    Full Text Available An effective anti-human immunodeficiency virus-1 (HIV-1 microbicide should exert its action in the absence of causing aberrant activation of topical immunity that will increase the risk of HIV acquisition. In the present study, we demonstrated that the vaginal application of cellulose sulfate (CS gel induced topical mucosal inflammatory responses; the addition of minocycline to CS gel could significantly attenuate the inflammation in a mice model. The combined gel of CS plus minocycline not only reduced the production of inflammatory cytokines in cervicovaginal lavages (CVLs, also down-regulated the activation of CD4+ T cells and the recruitment of other immune cells including HIV target cells into vaginal tissues. Furthermore, an In vitro HIV-1 pseudovirus infection inhibition assay showed that the combined gel decreased the infection efficacy of different subtypes of HIV-1 pseudoviruses compared with that of CS gel alone. These results implicate that minocycline could be integrated into microbicide formulation to suppress the aberrant activation of topical mucosal immunity and enhance the safety profile during the application of microbicides.

  13. The down regulation of target genes by photo activated DNA nanoscissors.

    Science.gov (United States)

    Tsai, Tsung-Lin; Shieh, Dar-Bin; Yeh, Chen-Sheng; Tzeng, Yonhua; Htet, Khant; Chuang, Kao-Shu; Hwu, Jih Ru; Su, Wu-Chou

    2010-09-01

    An artificial, targeted, light-activated nanoscissor (ATLANS) was developed for precision photonic cleavage of DNA at selectable target sequences. The ATLANS is comprised of nanoparticle core and a monolayer of hydrazone-modified triplex-forming oligonucleotides (TFOs), which recognize and capture the targeted DNA duplex. Upon photo-illumination (lambda = 460 nm), the attached hydrazone scissor specifically cleaves the targeted DNA at a pre-designed nucleotide pair. Electrophoretic mobility shift and co-precipitation assays revealed sequence-specific binding with the short-fragment and long-form plasmid DNA of both TFO and TFO-nanoparticle probes. Upon photo-illumination, ATLANS introduced a precise double-stranded break 12bp downstream the TFO binding sequence and down-regulated the target gene in HeLa cell system. Gold nanoparticles multiplexed the cutting efficiency and potential for simultaneous manipulation of multiple targets, as well as protected DNA from non-specific photo-damage. This photon-mediated DNA manipulation technology will facilitate high spatial and temporal precision in simultaneous silencing at the genome level, and advanced simultaneous manipulation of multiple targeted genes. PMID:20605206

  14. Nutlin-3 down-regulates retinoblastoma protein expression and inhibits muscle cell differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Walsh, Erica M. [Department of Biochemistry, Boston University School of Medicine, Boston, MA 02118 (United States); Niu, MengMeng; Bergholz, Johann [Center of Growth, Metabolism and Aging, College of Life Sciences, Sichuan University, Chengdu, 610014 China (China); Jim Xiao, Zhi-Xiong, E-mail: jxiao@bu.edu [Department of Biochemistry, Boston University School of Medicine, Boston, MA 02118 (United States); Center of Growth, Metabolism and Aging, College of Life Sciences, Sichuan University, Chengdu, 610014 China (China)

    2015-05-29

    The p53 tumor suppressor gene plays a critical role in regulation of proliferation, cell death and differentiation. The MDM2 oncoprotein is a major negative regulator for p53 by binding to and targeting p53 for proteasome-mediated degradation. The small molecule inhibitor, nutlin-3, disrupts MDM2-p53 interaction resulting in stabilization and activation of p53 protein. We have previously shown that nutlin-3 activates p53, leading to MDM2 accumulation as concomitant of reduced retinoblastoma (Rb) protein stability. It is well known that Rb is important in muscle development and myoblast differentiation and that rhabdomyosarcoma (RMS), or cancer of the skeletal muscle, typically harbors MDM2 amplification. In this study, we show that nutlin-3 inhibited myoblast proliferation and effectively prevented myoblast differentiation, as evidenced by lack of expression of muscle differentiation markers including myogenin and myosin heavy chain (MyHC), as well as a failure to form multinucleated myotubes, which were associated with dramatic increases in MDM2 expression and decrease in Rb protein levels. These results indicate that nutlin-3 can effectively inhibit muscle cell differentiation. - Highlights: • Nutlin-3 inhibits myoblast proliferation and prevents differentiation into myotubes. • Nutlin-3 increases MDM2 expression and down-regulates Rb protein levels. • This study has implication in nutlin-3 treatment of rhabdomyosarcomas.

  15. Down-regulation of the beacon gene expression in the regenerating rat adrenal cortex.

    Science.gov (United States)

    Ziolkowska, Agnieszka; Rucinski, Marcin; Tyczewska, Marianna; Belloni, Anna Sandra; Nowak, Magdalena; Nussdorfer, Gastone G; Malendowicz, Ludwik K

    2006-12-01

    Beacon, a hypothalamic peptide involved in the regulation of food intake, has been recently shown to be expressed in the adrenal cortex, and to inhibit its secretion and growth. To further characterize the role of beacon in the control of adrenal growth, we investigated the level of beacon gene expression in the regenerating rat adrenal cortex. Conventional reverse transcription-polymerase chain reaction (PCR) and immunocytochemistry demonstrated the expression of beacon mRNA and protein in the adrenals at both days 5 and 8 of regeneration after enucleation and contralateral adrenalectomy. Semiquantitative real time-PCR revealed a net down-regulation of beacon mRNA in the regenerating glands, as compared to the intact adrenal cortex of sham-operated animals. Beacon gene expression was higher at day 8 than at day 5 of regeneration. Mitotic index, as assayed by the stachmokinetic method with vincristin, was negligible in the intact adrenal, but greatly elevated in regenerating gland, with a higher index found at day 5 than at day 8 after surgery. Taken together our findings indicate that the level of beacon gene expression is inversely correlated with the proliferative activity of adrenocortical cells, and suggest that beacon might act as an endogenous inhibitor of adrenocortical growth in the rat.

  16. DOWN-REGULATION OF CYTOKINE SECRETION AND REPRESSION OF APOPTOSIS hDaxx IN MACROPHAGES

    Institute of Scientific and Technical Information of China (English)

    LIU An-yuan; WAN Yan-ping; TAN Li-zhi; WU Yi-mou; YU Min-jun; LIU Chuan-ai; Yin Wei-guo

    2005-01-01

    Objective: To investigate the regulation effects on LPS-mediated cytokine secretion and dexamethasone- induced apoptosis in macrophages by transient overexpression of hDaxx. Methods: An eukaryotic expression vector pEGFP/hDaxx, which could express a fusion protein GFP-Daxx, was transfected into macrophages. The expression and localization of GFP-hDaxx fusion protein was analyzed by fluorescent microscope and western blot. The effects of transient overexpression of GFP-hDaxx fusion protein on the lipopolysaccharide(LPS)-mediated secretion of TNF-( and IL-1( were determined by ELISA. Moreover, the dexamethasone-induced apoptosis was determined morphologically by Giemsa stain. Results: The results observed showed that GFP-hDaxx fusion protein overexpressed in macrophages and localized in nuclei but GFP in cytoplasm under fluorescent microscope. The overexpression of GFP-hDaxx fusion protein could be detected by Western blot with an antibody against C-terminal of hDaxx. In the group with overexpressed GFP-hDaxx fusion protein, the LPS-mediated cytokine secretion decreased remarkably at 1 h, 3 h, 6 h respectively after LPS stimulation, and the dexamethasone- induced apoptosis reduced notably at 6 h, 12 h and 24 h respectively after addition of dexamethasone. There were remarkable difference between pEGFP/hDaxx group and control group (P<0.01) at different time. Conclusion: Transient overexpression of hDaxx down-regulates LPS-mediated cytokine secretion in macrophages and inhibits dexamethasone-induced macrophages apoptosis.

  17. Down-regulation of the cardiac sarcoplasmic reticulum ryanodine channel in severely food-restricted rats

    Directory of Open Access Journals (Sweden)

    V.A. Vizotto

    2007-01-01

    Full Text Available We have shown that myocardial dysfunction induced by food restriction is related to calcium handling. Although cardiac function is depressed in food-restricted animals, there is limited information about the molecular mechanisms that lead to this abnormality. The present study evaluated the effects of food restriction on calcium cycling, focusing on sarcoplasmic Ca2+-ATPase (SERCA2, phospholamban (PLB, and ryanodine channel (RYR2 mRNA expressions in rat myocardium. Male Wistar-Kyoto rats, 60 days old, were submitted to ad libitum feeding (control rats or 50% diet restriction for 90 days. The levels of left ventricle SERCA2, PLB, and RYR2 were measured using semi-quantitative RT-PCR. Body and ventricular weights were reduced in 50% food-restricted animals. RYR2 mRNA was significantly decreased in the left ventricle of the food-restricted group (control = 5.92 ± 0.48 vs food-restricted group = 4.84 ± 0.33, P < 0.01. The levels of SERCA2 and PLB mRNA were similar between groups (control = 8.38 ± 0.44 vs food-restricted group = 7.96 ± 0.45, and control = 1.52 ± 0.06 vs food-restricted group = 1.53 ± 0.10, respectively. Down-regulation of RYR2 mRNA expressions suggests that chronic food restriction promotes abnormalities in sarcoplasmic reticulum Ca2+ release.

  18. Down-regulation of the alpha-2C adrenergic receptor: involvement of a serine/threonine motif in the third cytoplasmic loop

    OpenAIRE

    Deupree, Jean D; Borgeson, Claudia D.; Bylund, David B.

    2002-01-01

    Background The mechanisms by which alpha-2 adrenergic receptors are down-regulated following chronic exposure to agonist are not well understood. Interestingly, the human alpha-2C receptor does not down-regulate, whereas the opossum alpha-2C receptor does down-regulate. A comparison of the amino acid sequence of the third intracellular loop of these two receptors shows that the opossum alpha-2C receptor contains a potential G protein-coupled receptor kinase (GRK)phosphorylation motif (EESSTSE...

  19. Endothelial progenitor cell down-regulation in a mouse model of Kawasaki disease

    Institute of Scientific and Technical Information of China (English)

    LIU Jun-feng; DU Zhong-dong; CHEN Zhi; LU Dun-xiang; LI Li; GUAN Yun-qian; WAN Sui-gui

    2012-01-01

    Background Cardiovascular complications of Kawasaki disease (KD) are a common cause of heart disease in pediatric populations.Previous studies have suggested a role for endothelial progenitor cells (EPCs) in coronary artery lesions associated with KD.However,long-term observations of EPCs during the natural progression of this disorder are lacking.Using an experimental model of KD,we aimed to determine whether the coronary artery lesions are associated with down-regulation of EPCs.Methods To induce KD,C57BL/6 mice were administered an intraperitoneal injection of Lactobacillus casei cell wall extract (LCWE; phosphate buffered saline used as control vehicle).Study groups included:group A (14 days following LCWE injection),group B (56 days following LCWE injection) and group C (controls).Numbers of circulating EPCs (positively staining for both CD34 and FIk-1 while staining negative for CD45) were evaluated using flow cytometry.Bone marrow mononuclear cells were cultured in vitro to expand EPCs for functional analysis.In vitro EPC proliferation,adhesion and migration were assessed.Results The model was shown to exhibit similar coronary artery lesions to KD patients with coronary aneurysms.Numbers of circulating EPCs decreased significantly in the KD models (groups A and B) compared to controls ((0.017±0.008)% VS.(0.028±0.007)%,P<0.05 and (0.016±0.007)% vs.(0.028±0.007)%,P <0.05).Proliferative,adhesive and migratory properties of EPCs were markedly impaired in groups A and B.Conclusion Coronary artery lesions in KD occur as a consequence of impaired vascular injury repair,resulting from excess consumption of EPCs together with a functional impairment of bone marrow EPCs and their precursors.

  20. Down-regulation of CDH1 is associated with expression of SNAI1 in colorectal adenomas.

    Directory of Open Access Journals (Sweden)

    Feride Kroepil

    Full Text Available INTRODUCTION: Down-regulation of E-cadherin (CDH1 and epithelial-mesenchymal transition (EMT are considered critical events for invasion and metastasis of colorectal carcinoma. Here we tested whether the important regulators of E-cadherin expression SNAI1 and TWIST1 are already detectable in human colorectal adenomas. METHODS: RNA was extracted from a set of randomly selected formalin-fixed and paraffin-embedded (FFPE colorectal adenomas (n = 41 and normal colon mucosa (n = 10. Subsequently mRNA expression of CDH1, CDH2, SNAI1 and TWIST1 was analysed by quantitative RT-PCR analysis. CDH1 as well as SNAI1 protein expression were assessed by immunohistochemistry (IHC. RESULTS: SNAI1 mRNA was expressed in 78% (n = 32/41, TWIST1 mRNA in 41% (n = 17/41 and CDH2 mRNA in 41% (n = 17/41 of the colorectal adenoma tissue, while normal colon mucosa was negative for these transcription factors. We found a significant correlation between reduced CDH1 and the presence of SNAI1 mRNA expression and for combined SNAI1 and TWIST1 mRNA expression, respectively. A correlation between CDH2 mRNA expression and reduced CDH1 expression was not observed. We confirmed the relationship between SNAI1 expression and reduced E-cadherin expression on the protein level via IHC. CONCLUSION: Our data show that SNAI1 and Twist1 are already expressed in benign precursor lesions of colorectal cancer and that SNAI1 expression was significantly correlated with lower expression of CDH1. Whether these findings reflect true EMT and/or are a sign of a more aggressive biology need to be investigated in further studies.

  1. Insulin receptor activation and down-regulation by cationic lipid transfection reagents

    Directory of Open Access Journals (Sweden)

    Renström Ing-Marie

    2004-01-01

    Full Text Available Abstract Background Transfection agents comprised of cationic lipid preparations are widely used to transfect cell lines in culture with specific recombinant complementary DNA molecules. We have found that cells in culture are often resistant to stimulation with insulin subsequent to treatment with transfection agents such as LipofectAMINE 2000™ and FuGENE-6™. This is seen with a variety of different readouts, including insulin receptor signalling, glucose uptake into muscle cells, phosphorylation of protein kinase B and reporter gene activity in a variety of different cell types Results We now show that this is due in part to the fact that cationic lipid agents activate the insulin receptor fully during typical transfection experiments, which is then down-regulated. In attempts to circumvent this problem, we investigated the effects of increasing concentrations of LipofectAMINE 2000™ on insulin receptor phosphorylation in Chinese hamster ovary cells expressing the human insulin receptor. In addition, the efficiency of transfection that is supported by the same concentrations of transfection reagent was studied by using a green fluorescent protein construct. Our data indicate that considerably lower concentrations of LipofectAMINE 2000™ can be used than are recommended by the manufacturers. This is without sacrificing transfection efficiency markedly and avoids the problem of reducing insulin receptor expression in the cells. Conclusion Widely-used cationic lipid transfection reagents cause a state of insulin unresponsiveness in cells in culture due to fully activating and subsequently reducing the expression of the receptor in cells. This phenomenon can be avoided by reducing the concentration of reagent used in the transfection process.

  2. RETINOIC ACID DOWN-REGULATES BONE MORPHOGENETIC PROTEIN 7 EXPRESSION IN RAT WITH CLEFT PALATE

    Institute of Scientific and Technical Information of China (English)

    Lei Guo; Yu-yan Zhao; Shi-liang Zhang; Kui Liu; Xiao-yu Gao

    2008-01-01

    Objective To evaluate the effects of retinoic acid (RA) on expression of bone morphogenetic protein 7 (BMP-7)in rat fetus with cleft palate, and the effects of RA on proliferation and apoptosis of osteoblasts. Methods All-trans RA (ATRA) was used to induce congenital cleft palate in Wistar rat. BMP-7 mRNA expres-sion in maxillary bone tissue of fetal rats was measured by Northern blotting analysis. Flow cytometry and MTT assay were used to measure the apoptosis and proliferation of ATRA-treated MC-3T3-E1 cells. BMP-7 mRNA and protein ex-pressions in ATRA-treated MC-3T3-E1 cells were detected by RT-PCR and Western blotting analysis.Results ATRA could induce cleft palate of rat fetus. The incidence rate of cleft palate induced by 100 mg/kg AT-RA (45.5%) was significantly higher than 50 mg/kg ATRA (12.5%, P<0.05). BMP-7 mRNA expression de-creased in maxillary bone tissue of rat fetus with cleft palate. MC-3T3-E1 cells proliferation treated with 1 × 10-6 mol/L ATRA decreased by 60%, the cell apoptosis increased by 2 times. BMP-7 mR.NA and protein levels in MC-3T3-E1cells treated with 1 × 10-6 mol/L ATRA decreased by 60% and 80%, respectively, compared with ATRA-untreated ceils (P<0.05).Conclusions BMP-7 may play an important role in embryonic palate development RA may possess the ability to down-regulate cell proliferation through regulation of BMP-7 gene expression.

  3. MicroRNA-193b enhances tumor progression via down regulation of neurofibromin 1.

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    Michelle Lenarduzzi

    Full Text Available Despite improvements in therapeutic approaches for head and neck squamous cell carcinomas (HNSCC, clinical outcome has remained disappointing, with 5-year overall survival rates hovering around 40-50%, underscoring an urgent need to better understand the biological bases of this disease. We chose to address this challenge by studying the role of micro-RNAs (miRNAs in HNSCC. MiR-193b was identified as an over-expressed miRNA from global miRNA profiling studies previously conducted in our lab, and confirmed in HNSCC cell lines. In vitro knockdown of miR-193b in FaDu cancer cells substantially reduced cell proliferation, migration and invasion, along with suppressed tumour formation in vivo. By integrating in silico prediction algorithms with in vitro experimental mRNA profilings, plus mRNA expression data of clinical specimens, neurofibromin 1 (NF1 was identified to be a target of miR-193b. Concordantly, miR-193b knockdown decreased NF1 transcript and protein levels significantly. Luciferase reporter assays confirmed the direct interaction of miR-193b with NF1. Moreover, p-ERK, a downstream target of NF1 was also suppressed after miR-193b knockdown. FaDu cells treated with a p-ERK inhibitor (U0126 phenocopied the reduced cell proliferation, migration and invasion observed with miR-193b knockdown. Finally, HNSCC patients whose tumours expressed high levels of miR-193b experienced a lower disease-free survival compared to patients with low miR-193b expression. Our findings identified miR-193b as a potentially novel prognostic marker in HNSCC that drives tumour progression via down-regulating NF1, in turn leading to activation of ERK, resulting in proliferation, migration, invasion, and tumour formation.

  4. Down-regulation of Zac1 gene expression in rat white adipose tissue by androgens.

    Science.gov (United States)

    Mirowska, Agnieszka; Sledzinski, Tomasz; Smolenski, Ryszard T; Swierczynski, Julian

    2014-03-01

    ZAC1 is a zinc-finger protein transcription factor, a transcriptional cofactor for nuclear receptors, and a co-activator of nuclear receptors, which interacts with multiple signaling pathways affecting apoptosis, cell cycle arrest, and metabolism. Some data suggest that ZAC1 regulates the expression of genes associated with function of adipose tissue. Since there is no information about the levels of Zac1 gene expression in white adipose tissue (WAT), and the expression of several genes associated with metabolic function of WAT is significantly lower in male than female animals, we have examined: (a) the relative ZAC1 mRNA levels in some organs/tissues, including three main depots of WAT, in 3-month-old male rats; (b) the relative ZAC1 mRNA levels in WAT of male and female rats; (c) the effect of orchidectomy and orchidectomy with concomitant testosterone treatment on ZAC1 mRNA and protein levels; (d) the effect of ovariectomy and ovariectomy with concomitant 17β-estradiol treatment on ZAC1 mRNA levels; (e) the effect of dihydrotestosterone on ZAC1 mRNA levels in isolated adipocytes. Our results indicate that: (a) ZAC1 mRNA levels are relatively high in WAT in comparison with other organs/tissues; (b) ZAC1 mRNA levels in subcutaneous WAT are approximately 2-fold lower than in epididymal and retroperitoneal adipose tissue; (c) ZAC1 mRNA levels in WAT of adult female rats are approximately 2-fold higher than in male rats; (d) testosterone is inversely related to ZAC1 mRNA and protein levels in WAT of male rats; and (e) dihydrotestosterone decreases the ZAC1 mRNA levels in adipocytes in dose dependent manner. In conclusion, Zac1 gene is highly expressed in white adipose tissue of adult rats. Androgens could play an important role in down-regulation of the ZAC1 mRNA and protein levels in rats.

  5. Strategic down-regulation of attentional resources as a mechanism of proactive response inhibition.

    Science.gov (United States)

    Langford, Zachary D; Krebs, Ruth M; Talsma, Durk; Woldorff, Marty G; Boehler, C N

    2016-08-01

    Efficiently avoiding inappropriate actions in a changing environment is central to cognitive control. One mechanism contributing to this ability is the deliberate slowing down of responses in contexts where full response cancellation might occasionally be required, referred to as proactive response inhibition. The present electroencephalographic (EEG) study investigated the role of attentional processes in proactive response inhibition in humans. To this end, we compared data from a standard stop-signal task, in which stop signals required response cancellation ('stop-relevant'), to data where possible stop signals were task-irrelevant ('stop-irrelevant'). Behavioral data clearly indicated the presence of proactive slowing in the standard stop-signal task. A novel single-trial analysis was used to directly model the relationship between response time and the EEG data of the go-trials in both contexts within a multilevel linear models framework. We found a relationship between response time and amplitude of the attention-related N1 component in stop-relevant blocks, a characteristic that was fully absent in stop-irrelevant blocks. Specifically, N1 amplitudes were lower the slower the response time, suggesting that attentional resources were being strategically down-regulated to control response speed. Drift diffusion modeling of the behavioral data indicated that multiple parameters differed across the two contexts, likely suggesting the contribution from independent brain mechanisms to proactive slowing. Hence, the attentional mechanism of proactive response control we report here might coexist with known mechanisms that are more directly tied to motoric response inhibition. As such, our study opens up new research avenues also concerning clinical conditions that feature deficits in proactive response inhibition.

  6. Dexamethasone acutely down-regulates genes involved in steroidogenesis in stallion testes.

    Science.gov (United States)

    Ing, Nancy H; Forrest, David W; Riggs, Penny K; Loux, Shavahn; Love, Charlie C; Brinsko, Steven P; Varner, Dickson D; Welsh, Thomas H

    2014-09-01

    In rodents, livestock and primate species, a single dose of the synthetic glucocorticoid dexamethasone acutely lowers testosterone biosynthesis. To determine the mechanism of decreased testosterone biosynthesis, stallions were treated with 0.1mg/kg dexamethasone 12h prior to castration. Dexamethasone decreased serum concentrations of testosterone by 60% compared to saline-treated control stallions. Transcriptome analyses (microarrays, northern blots and quantitative PCR) of testes discovered that dexamethasone treatment decreased concentrations of glucocorticoid receptor alpha (NR3C1), alpha actinin 4 (ACTN4), luteinizing hormone receptor (LHCGR), squalene epoxidase (SQLE), 24-dehydrocholesterol reductase (DHCR24), glutathione S-transferase A3 (GSTA3) and aromatase (CYP19A1) mRNAs. Dexamethasone increased concentrations of NFkB inhibitor A (NFKBIA) mRNA in testes. SQLE, DHCR24 and GSTA3 mRNAs were predominantly expressed by Leydig cells. In man and livestock, the GSTA3 protein provides a major 3-ketosteroid isomerase activity: conversion of Δ(5)-androstenedione to Δ(4)-androstenedione, the immediate precursor of testosterone. Consistent with the decrease in GSTA3 mRNA, dexamethasone decreased the 3-ketosteroid isomerase activity in testicular extracts. In conclusion, dexamethasone acutely decreased the expression of genes involved in hormone signaling (NR3C1, ACTN4 and LHCGR), cholesterol synthesis (SQLE and DHCR24) and steroidogenesis (GSTA3 and CYP19A1) along with testosterone production. This is the first report of dexamethasone down-regulating expression of the GSTA3 gene and a very late step in testosterone biosynthesis. Elucidation of the molecular mechanisms involved may lead to new approaches to modulate androgen regulation of the physiology of humans and livestock in health and disease. PMID:25010478

  7. Down-regulation of sirtuin 3 is associated with poor prognosis in hepatocellular carcinoma after resection

    International Nuclear Information System (INIS)

    Sirtuin 3 (Sirt3), one of the seven Sirtuins family members, plays critical roles in the progression of multiple cancer types. However, its role in the prognosis of hepatocellular carcinoma (HCC) has not yet been investigated systematically. The correlation of Sirtuins expression with prognosis of HCC was determined by immunohistochemistry (IHC) in a large HCC patient cohort (n = 342). Expression of Sirt3 in tumoral and peritumoral tissues of HCC patients were further determined by western blotting (WB). IHC and WB studies both showed a decreased expression of Sirt3 in tumoral tissues compared with peritumoral tissues (P = 0.003 for IHC, P = 0.0042 for WB). Decreased expression of Sirt3 in both tumoral and peritumoral tissues was associated with increased recurrence probability and decreased overall survival rate by univariate analyses (intratumoral Sirt3: P = 0.011 for TTR, P = 0.001 for OS; peritumoral Sirt3: P = 0.017 for TTR, P = 0.023 for OS), the prognostic value was strengthened by multivariate analyses (intratumoral Sirt3: P = 0.031 for TTR, P = 0.001 for OS; peritumoral Sirt3: P = 0.047 for TTR, P = 0.031 for OS). Intratumoral Sirt3 also showed a favorable prognostic value in patients with BCLC stage A (TTR, P = 0.011; OS, P < 0.001). In addition, we found that IHC studies of other sirtuin members showed a decreased expression of Sirt2, Sirt4 and Sirt5 and an increased expression of Sirt1, Sirt6 and Sirt7 in intratumoral tissues compared with peritumoral tissues. In contrast to Sirt3, other members did not showed a remarkable correlation with HCC prognosis. Down-regulation of intratumoral and peritumoral Sirt3 were both associated with poor outcome in HCC, moreover, intratumoral Sirt3 was a favorable prognostic predictor in early stage patients

  8. Quantitative cell signalling analysis reveals down-regulation of MAPK pathway activation in colorectal cancer.

    LENUS (Irish Health Repository)

    Gulmann, Christian

    2009-08-01

    Mitogen-activated protein kinases (MAPK) are considered to play significant roles in colonic carcinogenesis and kinase inhibitor therapy has been proposed as a potential tool in the treatment of this disease. Reverse-phase microarray assays using phospho-specific antibodies can directly measure levels of phosphorylated protein isoforms. In the current study, samples from 35 cases of untreated colorectal cancer colectomies were laser capture-microdissected to isolate epithelium and stroma from cancer as well as normal (i.e. uninvolved) mucosa. Lysates generated from these four tissue types were spotted onto reverse-phase protein microarrays and probed with a panel of antibodies to ERK, p-ERK, p38, p-p38, p-JNK, MEK and p-MEK. Whereas total protein levels were unchanged, or slightly elevated (p38, p = 0.0025) in cancers, activated isoforms, including p-ERK, p-p38 and p-JNK, were decreased two- to four-fold in cancers compared with uninvolved mucosa (p < 0.0023 in all cases except for p-JNK in epithelium, where decrement was non-significant). This was backed up by western blotting. Dukes\\' stage B and C cancers displayed lower p-ERK and p-p38 expression than Dukes\\' stage A cancers, although this was not statistically significant. It is concluded that MAPK activity may be down-regulated in colorectal cancer and that further exploration of inhibitory therapy in this system should be carefully evaluated if this finding is confirmed in larger series.

  9. Down-regulation of microRNA-26a promotes mouse hepatocyte proliferation during liver regeneration.

    Directory of Open Access Journals (Sweden)

    Jian Zhou

    Full Text Available BACKGROUND: Inadequate liver regeneration (LR is still an unsolved problem in major liver resection and small-for-size syndrome post-living donor liver transplantation. A number of microRNAs have been shown to play important roles in cell proliferation. Herein, we investigated the role of miR-26a as a pivotal regulator of hepatocyte proliferation in LR. METHODOLOGY/PRINCIPAL FINDINGS: Adult male C57BL/6J mice, undergoing 70% partial hepatectomy (PH, were treated with Ad5-anti-miR-26a-LUC or Ad5-miR-26a-LUC or Ad5-LUC vector via portal vein. The animals were subjected to in vivo bioluminescence imaging. Serum and liver samples were collected to test liver function, calculate liver-to-body weight ratio (LBWR, document hepatocyte proliferation (Ki-67 staining, and investigate potential targeted gene expression of miR-26a by quantitative real-time PCR and Western blot. The miR-26a level declined during LR after 70% PH. Down-regulation of miR-26a by anti-miR-26a expression led to enhanced proliferation of hepatocytes, and both LBWR and hepatocyte proliferation (Ki-67(+ cells % showed an increased tendency, while liver damage, indicated by aspartate aminotransferase (AST, alanine aminotransferase (ALT and total bilirubin (T-Bil, was reduced. Furthermore, CCND2 and CCNE2, as possible targeted genes of miR-26a, were up-regulated. In addition, miR-26a over-expression showed converse results. CONCLUSIONS/SIGNIFICANCE: MiR-26a plays crucial role in regulating the proliferative phase of LR, probably by repressing expressions of cell cycle proteins CCND2 and CCNE2. The current study reveals a novel miRNA-mediated regulation pattern during the proliferative phase of LR.

  10. Impacts on the metabolome of down-regulating polyphenol oxidase in potato tubers.

    Science.gov (United States)

    Shepherd, Louise Vida Traill; Alexander, Colin James; Hackett, Christine Anne; McRae, Diane; Sungurtas, Julia Anne; Verrall, Susan Ramsay; Morris, Jennifer Anne; Hedley, Peter Edward; Rockhold, David; Belknap, William; Davies, Howard Vivian

    2015-06-01

    Tubers of potato (Solanum tuberosum L. cv. Estima) genetically modified to reduce polyphenol oxidase (PPO) activity and enzymatic discolouration were assessed for changes in the metabolome using Liquid Chromatography-Mass Spectrometry (LC-MS) and Gas Chromatography (GC)-MS. Metabolome changes induced over a 48 hour (h) period by tuber wounding (sliced transverse sections) were also assessed using two PPO antisense lines (asPPO) and a wild-type (WT) control. Data were analysed using Principal Components Analysis and Analysis of Variance to assess differences between genotypes and temporal changes post-tuber wounding (by slicing). The levels of 15 metabolites (out of a total of 134 that were detected) differed between the WT and asPPO lines in mature tubers at harvest. A considerably higher number (63) of these metabolites changed significantly over a 48 h period following tuber wounding. For individual metabolites the magnitude of the differences between the WT and asPPO lines at harvest were small compared with the impacts of tuber wounding on metabolite levels. Some of the observed metabolite changes are explicable in terms of pathways known to be affected by wound responses. Whilst some statistically significant interactions (11 metabolites) were observed between line and time after wounding, very few profiles were consistent when comparing the WT with both asPPO lines, and the underlying metabolites appeared to be random in terms of the pathways they occupy. Overall, mechanical damage to tubers has a considerably greater impact on the metabolite profile than any potential unintended effects resulting from the down-regulation of PPO gene expression. PMID:25417184

  11. Slug down-regulation by RNA interference inhibits invasion growth in human esophageal squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Zhang Shaoyan

    2011-05-01

    Full Text Available Abstract Background Esophageal squamous cell carcinoma (ESCC is one of the most aggressive carcinomas of the gastrointestinal tract. We assessed the relevance of Slug in measuring the invasive potential of ESCC cells in vitro and in vivo in immunodeficient mice. Methods We utilized RNA interference to knockdown Slug gene expression, and effects on survival and invasive carcinoma were evaluated using a Boyden chamber transwell assay in vitro. We evaluated the effect of Slug siRNA-transfection and Slug cDNA-transfection on E-cadherin and Bcl-2 expression in ESCC cells. A pseudometastatic model of ESCC in immunodeficient mice was used to assess the effects of Slug siRNA transfection on tumor metastasis development. Results The EC109 cell line was transfected with Slug-siRNA to knockdown Slug expression. The TE13 cell line was transfected with Slug-cDNA to increase Slug expression. EC109 and TE13 cell lines were tested for the expression of apoptosis-related genes bcl-2 and metastasis-related gene E-cadherin identified previously as Slug targets. Bcl-2 expression was increased and E-cadherin was decreased in Slug siRNA-transfected EC109 cells. Bcl-2 expression was increased and E-cadherin was decreased in Slug cDNA-transfected TE13 cells. Invasion of Slug siRNA-transfected EC109 cells was reduced and apoptosis was increased whereas invasion was greater in Slug cDNA-transfected cells. Animals injected with Slug siRNA-transfected EC109 cells exhihited fewer seeded nodes and demonstrated more apoptosis. Conclusions Slug down-regulation promotes cell apoptosis and decreases invasion capability in vitro and in vivo. Slug inhibition may represent a novel strategy for treatment of metastatic ESCC.

  12. Entrapment of carbon dioxide with chitosan-based core-shell particles containing changeable cores.

    Science.gov (United States)

    Dong, Yanrui; Fu, Yinghao; Lin, Xia; Xiao, Congming

    2016-08-01

    Water-soluble chitosan-based core-shell particles that contained changeable cores were successfully applied to anchor carbon dioxide. The entrapment capacity of the particles for carbon dioxide (EC) depended on the cores. It was found that EC of the particles contained aqueous cores was higher than that of the beads with water-soluble chitosan gel cores, which was confirmed with thermogravimetric analysis. In addition, calcium ions and sodium hydroxide were introduced within the particles to examine their effect on the entrapment. EC of the particles was enhanced with sodium hydroxide when the cores were WSC gel. The incorporation of calcium ions was helpful for stabilizing carbon dioxide through the formation of calcium carbonate, which was verified with Fourier transform infrared spectra and scanning electron microscopy/energy-dispersive spectrometry. This phenomenon meant the role of calcium ions for fixating carbon dioxide was significant. PMID:27174910

  13. Sheet-like carbon particles with graphene structures obtained from a Bunsen flame

    DEFF Research Database (Denmark)

    Ossler, Frederik; Wagner, Jakob Birkedal; Canton, Sophie E.;

    2010-01-01

    Carbon particle structures containing only a few graphene layers have been collected from a Bunsen (propane) diffusion flame in the low particle concentration pale yellow luminous regions close to the soot inception. These particles were sampled directly on transmission electron microscopy grids......-layered graphitic structures perpendicular to the graphene planes....

  14. Influence of adhesion to activated carbon particles on the viability of waterborne pathogenic bacteria under flow

    NARCIS (Netherlands)

    van der Mei, Henny C.; Atema-Smit, Jelly; Jager, Debbie; Langworthy, Don E.; Collias, Dimitris I.; Mitchell, Michael D.; Busscher, Henk J.

    2008-01-01

    In rural areas around the world, people often rely on water filtration plants using activated carbon particles for safe water supply. Depending on the carbon surface, adhering microorganisms die or grow to form a biofilm. Assays to assess the efficacy of activated carbons in bacterial removal do not

  15. Host defense against viral infection involves interferon mediated down-regulation of sterol biosynthesis.

    Directory of Open Access Journals (Sweden)

    Mathieu Blanc

    2011-03-01

    Full Text Available Little is known about the protective role of inflammatory processes in modulating lipid metabolism in infection. Here we report an intimate link between the innate immune response to infection and regulation of the sterol metabolic network characterized by down-regulation of sterol biosynthesis by an interferon regulatory loop mechanism. In time-series experiments profiling genome-wide lipid-associated gene expression of macrophages, we show a selective and coordinated negative regulation of the complete sterol pathway upon viral infection or cytokine treatment with IFNγ or β but not TNF, IL1β, or IL6. Quantitative analysis at the protein level of selected sterol metabolic enzymes upon infection shows a similar level of suppression. Experimental testing of sterol metabolite levels using lipidomic-based measurements shows a reduction in metabolic output. On the basis of pharmacologic and RNAi inhibition of the sterol pathway we show augmented protection against viral infection, and in combination with metabolite rescue experiments, we identify the requirement of the mevalonate-isoprenoid branch of the sterol metabolic network in the protective response upon statin or IFNβ treatment. Conditioned media experiments from infected cells support an involvement of secreted type 1 interferon(s to be sufficient for reducing the sterol pathway upon infection. Moreover, we show that infection of primary macrophages containing a genetic knockout of the major type I interferon, IFNβ, leads to only a partial suppression of the sterol pathway, while genetic knockout of the receptor for all type I interferon family members, ifnar1, or associated signaling component, tyk2, completely abolishes the reduction of the sterol biosynthetic activity upon infection. Levels of the proteolytically cleaved nuclear forms of SREBP2, a key transcriptional regulator of sterol biosynthesis, are reduced upon infection and IFNβ treatment at both the protein and de novo

  16. SLX4-SLX1 Protein-independent Down-regulation of MUS81-EME1 Protein by HIV-1 Viral Protein R (Vpr).

    Science.gov (United States)

    Zhou, Xiaohong; DeLucia, Maria; Ahn, Jinwoo

    2016-08-12

    Evolutionarily conserved structure-selective endonuclease MUS81 forms a complex with EME1 and further associates with another endonuclease SLX4-SLX1 to form a four-subunit complex of MUS81-EME1-SLX4-SLX1, coordinating distinctive biochemical activities of both endonucleases in DNA repair. Viral protein R (Vpr), a highly conserved accessory protein in primate lentiviruses, was previously reported to bind SLX4 to mediate down-regulation of MUS81. However, the detailed mechanism underlying MUS81 down-regulation is unclear. Here, we report that HIV-1 Vpr down-regulates both MUS81 and its cofactor EME1 by hijacking the host CRL4-DCAF1 E3 ubiquitin ligase. Multiple Vpr variants, from HIV-1 and SIV, down-regulate both MUS81 and EME1. Furthermore, a C-terminally truncated Vpr mutant and point mutants R80A and Q65R, all of which lack G2 arrest activity, are able to down-regulate MUS81-EME1, suggesting that Vpr-induced G2 arrest is not correlated with MUS81-EME1 down-regulation. We also show that neither the interaction of MUS81-EME1 with Vpr nor their down-regulation is dependent on SLX4-SLX1. Together, these data provide new insight on a conserved function of Vpr in a host endonuclease down-regulation.

  17. The CD3 gamma leucine-based receptor-sorting motif is required for efficient ligand-mediated TCR down-regulation

    DEFF Research Database (Denmark)

    von Essen, Marina; Menné, Charlotte; Nielsen, Bodil L;

    2002-01-01

    TCR down-regulation plays an important role in modulating T cell responses both during T cell development and in mature T cells. At least two distinct pathways exist for down-regulation of the TCR. One pathway is activated following TCR ligation and is dependent on tyrosine phosphorylation. The o...

  18. Down-regulation of adipogenesis of mesenchymal stem cells by oscillating high-gradient magnetic fields and mechanical vibration

    Science.gov (United States)

    Zablotskii, V.; Lunov, O.; Novotná, B.; Churpita, O.; Trošan, P.; HoláÅ, V.; Syková, E.; Dejneka, A.; Kubinová, Š.

    2014-09-01

    Nowadays, the focus in medicine on molecular genetics has resulted in a disregard for the physical basis of treatment even though many diseases originate from changes in cellular mechanics. Perturbations of the cellular nanomechanics promote pathologies, including cardiovascular disease and cancer. Furthermore, whilst the biological and therapeutic effects of magnetic fields are a well-established fact, to date the underlying mechanisms remain obscure. Here, we show that oscillating high-gradient magnetic field (HGMF) and mechanical vibration affect adipogenic differentiation of mesenchymal stem cells by the transmission of mechanical stress to the cell cytoskeleton, resulting in F-actin remodelling and subsequent down-regulation of adipogenic genes adiponectin, PPARγ, and AP2. Our findings propose an insight into the regulation of cellular nanomechanics, and provide a basis for better controlled down-regulation of stem cell adipogenesis by HGMF, which may facilitate the development of challenging therapeutic strategies suitable for the remote control of biological systems.

  19. Down-regulation of HSP27 sensitizes TRAIL-resistant tumor cell to TRAIL-induced apoptosis

    DEFF Research Database (Denmark)

    Zhuang, Hongqin; Jiang, Weiwei; Cheng, Wei;

    2010-01-01

    Tumor necrosis factor-alpha-related apoptosis-inducing ligand (TRAIL) has recently emerged as a cancer therapeutic agent because it preferentially induces apoptosis in human cancer over normal cells. Most tumor cells, including lung cancer cell line A549, unfortunately, are resistant to TRAIL...... siRNA on drug sensitization of A549 cells to TRAIL treatment. The results showed that treatment of A549 cells with HSP27 siRNA down-regulated HSP27 expression but did not induce significant apoptosis. However, combination of HSP27 siRNA with TRAIL-induced significant apoptosis in TRAIL-resistant A549...... cells. In addition to inducing caspases activation and apoptosis, combined treatment with HSP27 siRNA and TRAIL also increased JNK and p53 expression and activity. Collectively, these findings provide a conclusion that siRNA targeting of the HSP27 gene specifically down-regulated HSP27 expression in A...

  20. Collagen I-induced dendritic cells activation is regulated by TNF- production through down-regulation of IRF4

    Indian Academy of Sciences (India)

    Barun Poudel; Hyeon-Hui Ki; Young-Mi Lee; Dae-Ki Kim

    2015-03-01

    Previously we have shown that collagen I enhances the maturation and function of dendritic cells (DCs). Inflammatory mediators such as tumour necrosis factor (TNF)-, interleukin (IL)-1 and lipopolysaccharide (LPS) are also known to activate DCs. Here we investigated the involvement of TNF- on the collagen I-induced DCs activation. TNF-a neutralization inhibited collagen I-induced IL-12 secretions by DCs. Additionally, we observed suppression of collagen I-induced costimulatory molecules expression along with down-regulation of genes involved in DCs activation pathway. Furthermore, TNF- inhibition upon collagen Istimulation up-regulated the expression of interferon regulatory transcription factor IRF4, when compared to collagen I only treated cells. Collectively, our data demonstrate that collagen I induce TNF- production, which is crucial for the activation and function of DCs, through down-regulation of IRF4, and implicates the importance in development of anti- TNF- therapeutics for several inflammatory diseases.

  1. Effects of NANOG gene down-regulation on the apoptosis of T-cell acute lymphoblastic leukemia cells

    Institute of Scientific and Technical Information of China (English)

    曹江

    2014-01-01

    Objective To explore gene expression of NANOG in T-cell acute lymphoblastic leukemia(T-ALL)cell lines and the effects of NANOG gene down-regulation on apoptosis of leukemia cells.Methods Real-time PCR(RtPCR)and Western blot were used to detect the expression level of NANOG gene and protein in MOLT-4,CCRF-HSB2 and Jurkat cells.

  2. Sm protein down-regulation leads to defects in nuclear pore complex disassembly and distribution in C. elegans embryos

    OpenAIRE

    Joseph-Strauss, Daphna; Gorjánácz, Mátyás; Santarella-Mellwig, Rachel; Voronina, Ekaterina; Audhya, Anjon; Cohen-Fix, Orna

    2012-01-01

    Nuclear pore complexes (NPCs) are large macromolecular structures embedded in the nuclear envelope (NE), where they facilitate exchange of molecules between the cytoplasm and the nucleoplasm. In most cell types, NPCs are evenly distributed around the NE. However, the mechanisms dictating NPC distribution are largely unknown. Here, we used the model organism C. elegans to identify genes that affect NPC distribution during early embryonic divisions. We found that down-regulation of the Sm prote...

  3. Effects of down-regulation of clusterin by small interference RNA on human acute myeloid leukemia cells

    OpenAIRE

    Wang, Xiaoli; Liu, Ruidong; Wang, Yanxia; Cai, Hengjuan; Zhang, Lei

    2015-01-01

    Aims and background: Up-regulation of clusterin is associated with the survival and progression of various malignancies, and down-regulation of clusterin promotes apoptosis and inhibits invasion. The aim of this study was to explore the effect of clusterin small interference RNA (siRNA) on the proliferation, apoptosis and invasion of HL-60 acute myeloid leukemia (AML) cells. Methods: siRNA transfection was performed using Lipofectamine™2000 reagent. Relative protein expressions were quantifie...

  4. Organic Carbon Influences on Soil Particle Density and Rheological Properties

    Energy Technology Data Exchange (ETDEWEB)

    Blanco-Canqui, H; Lal, Rattan; Post, W M.; Izaurralde, R Cesar C.; Shipitalo, M. J.

    2006-07-01

    Soil particle density (rs) is not routinely measured and is assumed to range between 2.60 and 2.70 Mgm23 or to be a constant (2.65 Mgm23) when estimating essential properties such as porosity, and volumetric water and air relations. Values of rs for the same soil may, however, differ significantly from the standard range due to management induced changes in soil organic carbon (SOC) concentrations. We quantified the rs and Atterberg limits of a Rayne silt loam for five long-term (.22 yr) moldboard-plowed continuous corn (Zea mays L.; MP), no-till continuous corn (NT), no-till continuous corn with beef cattle manure (NTm), pasture, and forest systems.We also assessed the relationships of SOC concentration with rs and the Atterberg limits and the impact of rs on soil porosity. Mean rs across NT, NTm, and pasture (2.35 Mg m23) was |7% lower than that for MP in the 0- to 10-cm soil depth (2.52 Mg m23, P , 0.01). Forest had the lowest rs of all soils (1.79 Mg m23). The NTm caused a greater reduction in rs and a greater increase in SOC concentration, liquid limit (LL), plastic limit (PL), and plasticity index (PI) than NT. Surface soils under MP had the highest rs and rb and the lowest SOC concentration, LL, PL, and PI. The SOC concentration was correlated negatively with rs (r 2 5 0.75) and positively with Atterberg limits (r 2 . 0.64) at .20-cm depth. Estimates of soil porosity for NT, NTm, and pasture using the constant rs overestimated the ''true'' porosity by 12% relative to that using the measured rs.

  5. Hyperfine and Magnetic Characterization of Fe Particles Hosted in Carbon Nanocapsules

    Energy Technology Data Exchange (ETDEWEB)

    Coaquira, J. A. H., E-mail: coaquira@macbeth.if.usp.br; Rechenberg, H. R. [Universidade de Sao Paulo, Instituto de Fisica (Brazil); Marquina, C.; Ibarra, M. R. [Universidad de Zaragoza-CSIC, DFMC and ICMA (Spain); Benito, A. M.; Maser, W.; Munoz, E.; Martinez, M. T. [Instituto de Carboquimica CSIC (Spain)

    2001-05-15

    Iron particles encaged in carbon nanocapsules have been produced by the Kraetschmer-Huffmann carbon-arc discharge method. Soot, collarette and cathode samples have been characterized by Moessbauer spectroscopy and magnetic measurements in the temperature range 4.2-300 K. Different iron phases and iron-carbon solid solutions have been detected in our samples. The Einstein model has been used to evaluate the coupling constant between the particles and their environment, yielding values of the order 1-10 N/m. Irreversibilities observed at ZFC and FC curves for soot samples would suggest the presence of superparamagnetism only if the particles presented a blocking temperature above 300 K.

  6. The herpes simplex virus receptor nectin-1 is down-regulated after trans-interaction with glycoprotein D

    International Nuclear Information System (INIS)

    During herpes simplex virus (HSV) entry, membrane fusion occurs either on the cell surface or after virus endocytosis. In both cases, binding of glycoprotein D (gD) to a receptor such as nectin-1 or HVEM is required. In this study, we co-cultured cells expressing gD with nectin-1 expressing cells to investigate the effects of gD on nectin-1 at cell contacts. After overnight co-cultures with gD expressing cells, there was a down-regulation of nectin-1 in B78H1-C10, SY5Y, A431 and HeLa cells, which HSV enters by endocytosis. In contrast, on Vero cells, which HSV enters at the plasma membrane, nectin-1 was not down-regulated. Further analysis of B78H1-derived cells showed that nectin-1 down-regulation corresponds to the ability of gD to bind nectin-1 and is achieved by internalization and low-pH-dependent degradation of nectin-1. Moreover, gD is necessary for virion internalization in B78H1 cells expressing nectin-1. These data suggest that the determinants of gD-mediated internalization of nectin-1 may direct HSV to an endocytic pathway during entry

  7. DOWN-REGULATION OF C-MYC ONCOGENE DURING NGF-INDUCED DIFFERENTIATION OF NEUROBLASTOMA CELL LINES

    Institute of Scientific and Technical Information of China (English)

    陈杰; 刘彤华; AlonzoHRoss

    1994-01-01

    There may be a close relationship between myc oncogenes and carcinogenesis of human neuroblastoma.In previous studies.we were able to induce differentiation of certain neuroblastoma cell lines with NGF.In order to study gene regulation during differentiation.N-myc and c-myc cDNA probes were hybridized with RNA extracted from different cell lines before and after NGF treatment.It was found that cell lines which expressed N-myc did not express cmyc while those with c-myc did not express N-myc except for SHEP cell line which had neither c-myc nor N-myc expression.In NGF-induced differentiated neurblastoma cells,c-myc oncogene was down-regulated in comparison with the control samples.The time course of c-myc down-regulation was concomitant with the apperarance of orphological differentiation.In situ hybridization also showed remarkable reduction of c-myc oncogene expression in NGF-induced differentiated cells as compared with the untreated control cells.These results in dicate that down-regulation of c-myc concogene may be a key event during NGF-induced differentiation and overexpression of c-myc oncogene may ,at least partially,be responsible for the genesis of neuroblastoma.

  8. Dexamethasone down-regulates the expression of microRNA-155 in the livers of septic mice.

    Science.gov (United States)

    Wang, Zhong-hua; Liang, Yan-bing; Tang, Hao; Chen, Zhi-bin; Li, Zhen-yu; Hu, Xu-chu; Ma, Zhong-fu

    2013-01-01

    To investigate the expression of microRNA-155 (miRNA-155) in the livers of mice with lipopolysaccharide (LPS)-induced sepsis and to determine the role of dexamethasone (DXM) in the regulation of miRNA-155 expression, we pretreated mice with or without DXM prior to LPS exposure. Our study demonstrated that the expression of miRNA-155 and inflammatory factors increased in the liver tissues of mice with LPS-induced sepsis and that DXM down-regulated their expression in a dose-dependent manner. Moreover, DXM alone inhibited the expression of miRNA-155 to below the baseline level, but did not impact the expression of inflammatory factors, suggesting that the down-regulation of miRNA-155 by DXM may partially, but not completely, depend on the suppression of pro-inflammatory cytokines by DXM. Our data indicate that the overexpression of miRNA-155 in the livers of mice with LPS-induced sepsis may play an important role in the pathological processes of sepsis and that the down-regulation of miRNA-155 by DXM may be a novel mechanism regulating inflammation and immunity. PMID:24244697

  9. Dexamethasone down-regulates the expression of microRNA-155 in the livers of septic mice.

    Directory of Open Access Journals (Sweden)

    Zhong-hua Wang

    Full Text Available To investigate the expression of microRNA-155 (miRNA-155 in the livers of mice with lipopolysaccharide (LPS-induced sepsis and to determine the role of dexamethasone (DXM in the regulation of miRNA-155 expression, we pretreated mice with or without DXM prior to LPS exposure. Our study demonstrated that the expression of miRNA-155 and inflammatory factors increased in the liver tissues of mice with LPS-induced sepsis and that DXM down-regulated their expression in a dose-dependent manner. Moreover, DXM alone inhibited the expression of miRNA-155 to below the baseline level, but did not impact the expression of inflammatory factors, suggesting that the down-regulation of miRNA-155 by DXM may partially, but not completely, depend on the suppression of pro-inflammatory cytokines by DXM. Our data indicate that the overexpression of miRNA-155 in the livers of mice with LPS-induced sepsis may play an important role in the pathological processes of sepsis and that the down-regulation of miRNA-155 by DXM may be a novel mechanism regulating inflammation and immunity.

  10. Reversal of islet GIP receptor down-regulation and resistance to GIP by reducing hyperglycemia in the Zucker rat

    International Nuclear Information System (INIS)

    In type 2 diabetes (T2DM) β-cell responsiveness to glucose-dependent insulinotropic polypeptide (GIP) is reduced. In a model of T2DM, the VDF Zucker rat, GIP receptor mRNA and protein levels were shown to be down-regulated. Possible restoration of responsiveness to GIP in Zucker rats by reducing hyperglycemia has been examined. ZDF rats with extreme hyperglycemia demonstrated greater islet GIP receptor mRNA down-regulation (94.3 ± 3.8%) than ZF rats (48.8 ± 22.8%). GIP receptor mRNA levels in ZDF rats returned to 83.0 ± 17.9% of lean following normalization of hyperglycemia by phlorizin treatment and pancreas perfusions demonstrated markedly improved GIP responsiveness. Treatment of VDF rats with a DP IV inhibitor (P32/98) resulted in improved glucose tolerance and restored sensitivity to GIP in isolated pancreata. These findings support the proposal that GIP receptor down-regulation in rodent T2DM is secondary to chronic hyperglycemia and that normalization of glycemia can restore GIP sensitivity

  11. Central Nervous System Proteomics in Animal Model of Multiple Sclerosis Revealed Down-Regulation of Mithochondrial Proteins

    Directory of Open Access Journals (Sweden)

    Abolhassan Shahzadeh Fazeli

    2009-01-01

    Full Text Available Objective: Detection of central nervous system (CNS molecular defects in an animal modelof multiple sclerosis.Materials and Methods: Experimental autoimmune encephalomyelitis (EAE was inducedby a myelin oligodendrocyte glycoprotein. Protein expression profiles in the central nervoussystem between healthy clinical scores 1 and 3 of EAE were studied using a two dimensionalelectrophoresis based proteomics approach coupled with MALDI TOF/TOF massspectrometry.Results: We identified 8 mitochondrial proteins that were differentially expressed in CNS, allof them down-regulated in scores 1 and/or 3. Of these, 5 proteins belong to the mitochondrialrespiratory chain including: NADH dehydrogenase (ubiquinone Fe-S protein 8, cytochromec oxidase Va, cytochrome c oxidase Vb, ATP5B, NADH dehydrogenase (ubiquinone flavoprotein2. We also observed down-regulation of three other mitochondrial proteins including:glutaredoxin 5, estradiol 17 beta-dehydrogenase 8 and isocitrate dehydrogenase.Conclusion: Down-regulation of mitochondrial proteins supported the hypothesis thathypoxia-like tissue injury in multiple sclerosis (MS lesions may be due to mitochondrialimpairment.

  12. Is telomerase reactivation associated with the down-regulation of TGF β receptor-II expression in human breast cancer?

    Directory of Open Access Journals (Sweden)

    Thomas Valene

    2003-07-01

    Full Text Available Abstract Background Telomerase is a ribonucleoprotein that synthesizes telomeres and plays an important role in chromosomal stability and cellular immortalisation. Telomerase activity is detectable in most human cancers but not in normal somatic cells. TGF beta (transforming growth factor beta is a member of a family of cytokines that are essential for cell survival and seems to be down-regulated in human cancer. Recent in vitro work using human breast cancer cell lines has suggested that TGF beta down-regulates the expression of hTERT (human telomerase reverse transcriptase : the catalytic subunit of telomerase. We have therefore hypothesised that telomerase reactivation is associated with reduced immunohisto-chemical expression of TGF beta type II receptor (RII in human breast cancer. Methods TGF beta RII immunohistochemical expression was determined in 24 infiltrating breast carcinomas with known telomerase activity (17 telomerase-positive and 7 telomerase-negative. Immunohistochemical expression of TGF beta RII was determined by a breast pathologist who was blinded to telomerase data. Results TGF beta RII was detected in all lesions. The percentage of stained cells ranged from 1–100%. The difference in TGF beta RII expression between telomerase positive and negative tumours was not statistically significant (p = 1.0. Conclusion The results of this pilot study suggest that there is no significant association between telomerase reactivation and TGF-beta RII down-regulation in human breast cancer.

  13. Internalization and down-regulation of the human epidermal growth factor receptor are regulated by the carboxyl-terminal tyrosines

    DEFF Research Database (Denmark)

    Helin, K; Beguinot, L

    1991-01-01

    with receptors in which 1, 2, or all 3 tyrosines were changed to phenylalanines. The triple point mutant EGF-R, expressed in NIH-3T3, exhibited low autophosphorylation in vivo, low biological and reduced kinase activities. Single and double point mutants were down-regulated, as well as wild type EGF-R......The C terminus of the epidermal growth factor receptor (EGF-R) contains three tyrosines (Y1068, Y1148, and Y1173) which correspond to the major autophosphorylation sites. To investigate the role of the tyrosines in internalization and down-regulation of the EGF-R, mutational analysis was performed...... in response to EGF showing a half-life of about 1 h. Degradation of the triple point mutant, however, was impaired and resulted in a half-life of 4 h in the presence of EGF. EGF-dependent down-regulation of surface receptors was decreased in the triple point mutant EGF-R as was internalization and degradation...

  14. Fasting induces CART down-regulation in the zebrafish nervous system in a cannabinoid receptor 1-dependent manner.

    Science.gov (United States)

    Nishio, Shin-Ichi; Gibert, Yann; Berekelya, Liubov; Bernard, Laure; Brunet, Frédéric; Guillot, Etienne; Le Bail, Jean-Christophe; Sánchez, Juan Antonio; Galzin, Anne Marie; Triqueneaux, Gerard; Laudet, Vincent

    2012-08-01

    Central and peripheral mechanisms modulate food intake and energy balance in mammals and the precise role of the type 1 cannabinoid receptor (CB1) in these processes is still being explored. Using the zebrafish, Danio rerio, we show that rimonabant, a CB1-specific antagonist with an EC(50) of 5.15 × 10(-8) m, decreases embryonic yolk sac reserve use. We reveal a developmental overlap between CART genes and CB1 expression in the hypothalamus and medulla oblongata, two brain structures that play crucial roles in appetite regulation in mammals. We show that morpholino knockdown of CB1 or fasting decreases cocaine- and amphetamine-related transcript (CART)-3 expression. Strikingly, this down-regulation occurs only in regions coexpressing CB1 and CART3, reinforcing the link between CB1, CART, and appetite regulation. We show that rimonabant treatment impairs the fasting-induced down-regulation of CART expression in specific brain regions, whereas vehicle alone-treated embryos do not display this rescue of CART expression. Our data reveal that CB1 lies upstream of CART and signals the appetite through the down-regulation of CART expression. Thus, our results establish the zebrafish as a promising system to study appetite regulation. PMID:22700585

  15. Synthesis and characterization of SnO2 nano particles for carbon absorbing applications

    Directory of Open Access Journals (Sweden)

    V. Ratchagar

    2016-03-01

    Full Text Available The SnO2 nano particles was synthesized by Microwave assisted technique. From the powder XRD the particle size was calculated using Scherrer formula, it from 57 nm. The absorption spectrum was recorded from 1100 nm to 190 nm, and the optical band gap was calculated using Touc plot. The band gap value 3.16 eV. The functional groups were confirmed by FTIR spectrum. The FE-SEM analysis reveals the morphology of SnO2 nano particles. The synthesized SnO2 nano particles were used as a catalyst to reduce carbon from automobiles fume. The detailed study on carbon emission was reported.

  16. Morphology and Optical Properties of Black-Carbon Particles Relevant to Engine Emissions

    Science.gov (United States)

    Michelsen, H. A.; Bambha, R.; Dansson, M. A.; Schrader, P. E.

    2013-12-01

    Black-carbon particles are believed to have a large influence on climate through direct radiative forcing, reduction of surface albedo of snow and ice in the cryosphere, and interaction with clouds. The optical properties and morphology of atmospheric particles containing black carbon are uncertain, and characterization of black carbon resulting from engines emissions is needed. Refractory black-carbon particles found in the atmosphere are often coated with unburned fuel, sulfuric acid, water, ash, and other combustion by-products and atmospheric constituents. Coatings can alter the optical and physical properties of the particles and therefore change their optical properties and cloud interactions. Details of particle morphology and coating state can also have important effects on the interpretation of optical diagnostics. A more complete understanding of how coatings affect extinction, absorption, and incandescence measurements is needed before these techniques can be applied reliably to a wide range of particles. We have investigated the effects of coatings on the optical and physical properties of combustion-generated black-carbon particles using a range of standard particle diagnostics, extinction, and time-resolved laser-induced incandescence (LII) measurements. Particles were generated in a co-flow diffusion flame, extracted, cooled, and coated with oleic acid. The diffusion flame produces highly dendritic soot aggregates with similar properties to those produced in diesel engines, diffusion flames, and most natural combustion processes. A thermodenuder was used to remove the coating. A scanning mobility particle sizer (SMPS) was used to monitor aggregate sizes; a centrifugal particle mass analyzer (CPMA) was used to measure coating mass fractions, and transmission electron microscopy (TEM) was used to characterize particle morphologies. The results demonstrate important differences in optical measurements between coated and uncoated particles.

  17. Mutation of Arabidopsis HY1 causes UV-C hypersensitivity by impairing carotenoid and flavonoid biosynthesis and the down-regulation of antioxidant defence.

    Science.gov (United States)

    Xie, Yanjie; Xu, Daokun; Cui, Weiti; Shen, Wenbiao

    2012-06-01

    Previous pharmacological results confirmed that haem oxygenase-1 (HO-1) is involved in protection of cells against ultraviolet (UV)-induced oxidative damage in soybean [Glycine max (L.) Merr.] seedlings, but there remains a lack of genetic evidence. In this study, the link between Arabidopsis thaliana HO-1 (HY1) and UV-C tolerance was investigated at the genetic and molecular levels. The maximum inducible expression of HY1 in wild-type Arabidopsis was observed following UV-C irradiation. UV-C sensitivity was not observed in ho2, ho3, and ho4 single and double mutants. However, the HY1 mutant exhibited UV-C hypersensitivity, consistent with the observed decreases in chlorophyll content, and carotenoid and flavonoid metabolism, as well as the down-regulation of antioxidant defences, thereby resulting in severe oxidative damage. The addition of the carbon monoxide donor carbon monoxide-releasing molecule-2 (CORM-2), in particular, and bilirubin (BR), two catalytic by-products of HY1, partially rescued the UV-C hypersensitivity, and other responses appeared in the hy1 mutant. Transcription factors involved in the synthesis of flavonoid or UV responses were induced by UV-C, but reduced in the hy1 mutant. Overall, the findings showed that mutation of HY1 triggered UV-C hypersensitivity, by impairing carotenoid and flavonoid synthesis and antioxidant defences.

  18. Interaction forces between waterborne bacteria and activated carbon particles

    NARCIS (Netherlands)

    Busscher, Henk J.; Dijkstra, Rene J. B.; Langworthy, Don E.; Collias, Dimitris I.; Bjorkquist, David W.; Mitchell, Michael D.; Van der Mei, Henny C.

    2008-01-01

    Activated carbons remove waterborne bacteria from potable water systems through attractive Lifshitz-van der Waals forces despite electrostatic repulsion between negatively charged cells and carbon surfaces. In this paper we quantify the interaction forces between bacteria with negatively and positiv

  19. Effect of large aspect ratio of biomass particles on carbon burnout in a utility boiler

    Energy Technology Data Exchange (ETDEWEB)

    D. Gera; M.P. Mathur; M.C. Freeman; Allen Robinson [Fluent, Inc./NETL, Morgantown, WV (United States)

    2002-12-01

    This paper reports on the development and validation of comprehensive combustion sub models that include the effect of large aspect ratio of biomass (switchgrass) particles on carbon burnout and temperature distribution inside the particles. Temperature and carbon burnout data are compared from two different models that are formulated by assuming (i) the particles are cylindrical and conduct heat internally, and (ii) the particles are spherical without internal heat conduction, i.e., no temperature gradient exists inside the particle. It was inferred that the latter model significantly underpredicted the temperature of the particle and, consequently, the burnout. Additionally, some results from cofiring biomass (10% heat input) with pulverized coal (90% heat input) are compared with the pulverized coal (100% heat input) simulations and coal experiments in a tangentially fired 150 MW{sub e} utility boiler. 26 refs., 7 figs., 4 tabs.

  20. THE INFLUENCE OF CARBON BURNOUT ON SUBMICRON PARTICLE FORMATION FROM EMULSIFIED FUEL OIL COMBUSTION

    Science.gov (United States)

    The paper gives results of an examination of particle behavior and particle size distributions from the combustion of different fuel oils and emulsified fuels in three experimental combusators. Results indicate that improved carbon (C) burnout from fule oil combustion, either by...

  1. A novel method of preparing metallic Janus silica particles using supercritical carbon dioxide

    NARCIS (Netherlands)

    Yang, Qiuyan; de Vries, Marcel H; Picchioni, Francesco; Loos, Katja

    2013-01-01

    In this study, we demonstrate a novel fabrication method to prepare metallic Janus silica particles by embedding nanosized silica particles on a spherical polystyrene (PS) substrate in supercritical carbon dioxide (sc CO2), followed by labelling with gold nanoparticles on the exposed part of the sil

  2. Identification of phenylalanine 346 in the rat growth hormone receptor as being critical for ligand-mediated internalization and down-regulation

    DEFF Research Database (Denmark)

    Allevato, G; Billestrup, N; Goujon, L;

    1995-01-01

    in this domain revealed that phenylalanine 346 is required for internalization. Receptor down-regulation in transiently transfected COS-7 cells was also dependent upon the phenylalanine 346 residue of the GHR, since no GH-induced down-regulation was observed in cells expressing the F346A GHR mutant. In contrast......, the ability to stimulate transcription of the serine protease inhibitor 2.1 promoter by the GHR was not affected by the phenylalanine 346 to alanine mutation. These results demonstrate that phenylalanine 346 is essential for GHR internalization and down-regulation but not for transcriptional signaling...

  3. Intracellular adenosine 3',5'-phosphate formation is essential for down-regulation of surface adenosine 3',5'-phosphate receptors in Dictyostelium

    OpenAIRE

    Van Haastert, Peter J. M.

    1994-01-01

    Dictyostelium discoideum cells contain cell surface cyclic AMP (cAMP) receptors that bind cAMP as a first messenger and intracellular cAMP receptors that bind cAMP as a second messenger. Prolonged incubation of Dictyostelium cells with cAMP induces a sequential process of phosphorylation, sequestration and down-regulation of the surface receptors. The role of intracellular cAMP in down-regulation of surface receptors was investigated. Down-regulation of receptors does not occur under conditio...

  4. Strong spectral dependence of light absorption by organic carbon particles formed by propane combustion

    OpenAIRE

    Schnaiter, M.; Gimmler, M.; I. Llamas; Linke, C.; C. Jäger; Mutschke, H.

    2006-01-01

    International audience We have measured the extinction and absorption cross sections of carbon particles emitted by a propane diffusion flame both in an aerosol chamber and on size-segregated samples deposited on optical windows. The absorption cross section, the single scattering albedo, and the Ångström exponent show drastic dependencies both on the C/O ratio and on the particle size. This is interpretated as being due to the appearance of nucleation modes of smaller organic particles at...

  5. Virtual Experiments Enable Exploring and Challenging Explanatory Mechanisms of Immune-Mediated P450 Down-Regulation.

    Science.gov (United States)

    Petersen, Brenden K; Ropella, Glen E P; Hunt, C Anthony

    2016-01-01

    Hepatic cytochrome P450 levels are down-regulated during inflammatory disease states, which can cause changes in downstream drug metabolism and hepatotoxicity. Long-term, we seek sufficient new insight into P450-regulating mechanisms to correctly anticipate how an individual's P450 expressions will respond when health and/or therapeutic interventions change. To date, improving explanatory mechanistic insight relies on knowledge gleaned from in vitro, in vivo, and clinical experiments augmented by case reports. We are working to improve that reality by developing means to undertake scientifically useful virtual experiments. So doing requires translating an accepted theory of immune system influence on P450 regulation into a computational model, and then challenging the model via in silico experiments. We build upon two existing agent-based models-an in silico hepatocyte culture and an in silico liver-capable of exploring and challenging concrete mechanistic hypotheses. We instantiate an in silico version of this hypothesis: in response to lipopolysaccharide, Kupffer cells down-regulate hepatic P450 levels via inflammatory cytokines, thus leading to a reduction in metabolic capacity. We achieve multiple in vitro and in vivo validation targets gathered from five wet-lab experiments, including a lipopolysaccharide-cytokine dose-response curve, time-course P450 down-regulation, and changes in several different measures of drug clearance spanning three drugs: acetaminophen, antipyrine, and chlorzoxazone. Along the way to achieving validation targets, various aspects of each model are falsified and subsequently refined. This iterative process of falsification-refinement-validation leads to biomimetic yet parsimonious mechanisms, which can provide explanatory insight into how, where, and when various features are generated. We argue that as models such as these are incrementally improved through multiple rounds of mechanistic falsification and validation, we will generate

  6. Down-regulation of transcription of the proapoptotic gene BNip3 in cultured astrocytes by murine coronavirus infection

    International Nuclear Information System (INIS)

    Murine coronavirus mouse hepatitis virus (MHV) causes encephalitis and demyelination in the central nervous system of susceptible rodents. Astrocytes are the major target for MHV persistence. However, the mechanisms by which astrocytes survive MHV infection and permit viral persistence are not known. Here we performed DNA microarray analysis on differential gene expression in astrocyte DBT cells by MHV infection and found that the mRNA of the proapoptotic gene BNip3 was significantly decreased following MHV infection. This finding was further confirmed by quantitative reverse transcription-polymerase chain reaction, Western blot analysis, and BNip3-promoter-luciferase reporter system. Interestingly, infection with live and ultraviolet light-inactivated viruses equally repressed BNip3 expression, indicating that the down-regulation of BNip3 expression does not require virus replication and is mediated during cell entry. Furthermore, treatment of cells with chloroquine, which blocks the acidification of endosomes, significantly inhibited the repression of the BNip3 promoter activity induced by the acidic pH-dependent MHV mutant OBLV60, which enters cells via endocytosis, indicating that the down-regulation of BNip3 expression is mediated by fusion between viral envelope and cell membranes during entry. Deletion analysis showed that the sequence between nucleotides 262 and 550 of the 588-base-pair BNip3 promoter is necessary and sufficient for driving the BNip3 expression and that it contains signals that are responsible for MHV-induced down-regulation of BNip3 expression in DBT cells. These results may provide insights into the mechanisms by which MHV evades host antiviral defense and promotes cell survival, thereby allowing its persistence in the host astrocytes

  7. SPAK and OSR1 Dependent Down-Regulation of Murine Renal Outer Medullary K+ Channel ROMK1

    Directory of Open Access Journals (Sweden)

    Bernat Elvira

    2014-09-01

    Full Text Available Background/Aims: The kinases SPAK (SPS1-related proline/alanine-rich kinase and OSR1 (oxidative stress-responsive kinase 1 participate in the regulation of the NaCl cotransporter NCC and the Na+,K+,2Cl- cotransporter NKCC2. The kinases are regulated by WNK (with-no-K[Lys] kinases. Mutations of genes encoding WNK kinases underly Gordon's syndrome, a monogenic disease leading to hypertension and hyperkalemia. WNK kinases further regulate the renal outer medullary K+ channel ROMK1. The present study explored, whether SPAK and/or OSR1 have similarly the potential to modify the activity of ROMK1. Methods: ROMK1 was expressed in Xenopus oocytes with or without additional expression of wild-type SPAK, constitutively active T233ESPAK, catalytically inactive D212ASPAK, wild-type OSR1, constitutively active T185EOSR1 and catalytically inactive D164AOSR1. Channel activity was determined utilizing dual electrode voltage clamp and ROMK1 protein abundance in the cell membrane utilizing chemiluminescence of ROMK1 containing an extracellular hemagglutinin epitope (ROMK1-HA. Results: ROMK1 activity and ROMK1-HA protein abundance were significantly down-regulated by wild-type SPAK and T233ESPAK, but not by D212ASPAK. Similarly, ROMK1 activity and ROMK1-HA protein abundance were significantly down-regulated by wild-type OSR1 and T185EOSR1, but not by D164AOSR1. Conclusion: ROMK1 protein abundance and activity are down-regulated by SPAK and OSR1.

  8. MicroRNA-122 down-regulation is involved in phenobarbital-mediated activation of the constitutive androstane receptor.

    Directory of Open Access Journals (Sweden)

    Ryota Shizu

    Full Text Available Constitutive androstane receptor (CAR is a nuclear receptor that regulates the transcription of target genes, including CYP2B and 3A. Phenobarbital activates CAR, at least in part, in an AMP-activated protein kinase (AMPK-dependent manner. However, the precise mechanisms underlying phenobarbital activation of AMPK are still unclear. In the present study, it was demonstrated that phenobarbital administration to mice decreases hepatic miR-122, a liver-enriched microRNA involved in both hepatic differentiation and function. The time-course change in the phenobarbital-mediated down-regulation of miR-122 was inversely correlated with AMPK activation. Phenobarbital decreased primary miR-122 to approximately 25% of the basal level as early as 1 h and suppressed transactivity of mir-122 promoter in HuH-7 cells, suggesting that the down-regulation occurred at the transcriptional level. AMPK activation by metformin or 5-aminoimidazole-4-carboxamide 1-β-D-ribonucleoside had no evident effect on miR-122 levels. An inhibitory RNA specific for miR-122 increased activated AMPK and CAR-mediated trancactivation of the phenobarbital-responsive enhancer module in HepG2 cells. Conversely, the reporter activity induced by the ectopic CAR was almost completely suppressed by co-transfection with the miR-122 mimic RNA. GFP-tagged CAR was expressed in the cytoplasm in addition to the nucleus in the majority of HuH-7 cells in which miR-122 was highly expressed. Co-transfection of the mimic or the inhibitor RNA for miR-122 further increased or decreased, respectively, the number of cells that expressed GFP-CAR in the cytoplasm. Taken together, these results suggest that phenobarbital-mediated down-regulation of miR-122 is an early and important event in the AMPK-dependent CAR activation and transactivation of its target genes.

  9. MicroRNA-122 down-regulation is involved in phenobarbital-mediated activation of the constitutive androstane receptor.

    Science.gov (United States)

    Shizu, Ryota; Shindo, Sawako; Yoshida, Takemi; Numazawa, Satoshi

    2012-01-01

    Constitutive androstane receptor (CAR) is a nuclear receptor that regulates the transcription of target genes, including CYP2B and 3A. Phenobarbital activates CAR, at least in part, in an AMP-activated protein kinase (AMPK)-dependent manner. However, the precise mechanisms underlying phenobarbital activation of AMPK are still unclear. In the present study, it was demonstrated that phenobarbital administration to mice decreases hepatic miR-122, a liver-enriched microRNA involved in both hepatic differentiation and function. The time-course change in the phenobarbital-mediated down-regulation of miR-122 was inversely correlated with AMPK activation. Phenobarbital decreased primary miR-122 to approximately 25% of the basal level as early as 1 h and suppressed transactivity of mir-122 promoter in HuH-7 cells, suggesting that the down-regulation occurred at the transcriptional level. AMPK activation by metformin or 5-aminoimidazole-4-carboxamide 1-β-D-ribonucleoside had no evident effect on miR-122 levels. An inhibitory RNA specific for miR-122 increased activated AMPK and CAR-mediated trancactivation of the phenobarbital-responsive enhancer module in HepG2 cells. Conversely, the reporter activity induced by the ectopic CAR was almost completely suppressed by co-transfection with the miR-122 mimic RNA. GFP-tagged CAR was expressed in the cytoplasm in addition to the nucleus in the majority of HuH-7 cells in which miR-122 was highly expressed. Co-transfection of the mimic or the inhibitor RNA for miR-122 further increased or decreased, respectively, the number of cells that expressed GFP-CAR in the cytoplasm. Taken together, these results suggest that phenobarbital-mediated down-regulation of miR-122 is an early and important event in the AMPK-dependent CAR activation and transactivation of its target genes. PMID:22815988

  10. Water deficit down-regulates miR398 and miR408 in pea (Pisum sativum L.).

    Science.gov (United States)

    Jovanović, Živko; Stanisavljević, Nemanja; Mikić, Aleksandar; Radović, Svetlana; Maksimović, Vesna

    2014-10-01

    MicroRNAs (miRNAs), recently recognized as important regulator of gene expression at posttranscriptional level, have been found to be involved in plant stress responses. The observation that some miRNAs are up- or down regulated by stress implies that they could play vital roles in plant resistance to abiotic and biotic stress. We investigated the effect of water stress treatment during 10 days on expression of conserved miRNAs-miR398a/b and miR408 in pea plants. This time frame reflects the changes as close as possible to the changes where water stress causes visible effects under field condition. It was observed that dehydration strongly down regulates the expression of both miR398a/b and miR408 in pea roots and shoots. The down-regulation of miR398a/b and the up-regulation of potential target genes - copper superoxide dismutase, CSD1, highlight the involvement of this miRNA in pea stress response. To the contrary, the mRNA level of cytochrome c oxidase subunit 5 (COX5b) did not change in roots and shoots of water-stressed plants, compared to control (well) hydrated plants. This suggests that COX5b is not the target of miR398, or that its expression is regulated by some other mechanism. P1B-ATPase expression increased during water deficit only in the shoots of pea; in the roots there were no changes in expression. Our results help to understand the possible role of investigated miRNAs and their contribution to pea capacity to cope with water deficit.

  11. Down-Regulation of Notchl and NF-κB by Curcumin in Breast Cancer Cells MDA-MB-231

    Institute of Scientific and Technical Information of China (English)

    LONG Li; CAO You-de

    2008-01-01

    Objective:To test whether the down-regulation of Notch1 gene expression by curcumin could inhibit cell growth and induce apoptosis,which may be associated mechanistically with the down-regulation of NF-κB in breast cancer cells. Methods:Breast cancer cell lines MDA-MB-231 were cultured in vitro and treated with different dosages of curcumin(0,1.25,5.0,20.0μmol/L)for dose-dependent assay and different time(0,24,48,72 h)at the dosage of 5.0μmol/L for time course assay.The changes of the mRNA and protein expression of Notch1 and NF-κB were measured by RT-PCR and Western Blot,and MTT assay was used to measure the change of proliferation. Results:The mRNA and protein levels of Notch 1 and NF-κB were decreased significantly in human breast cancer cell line with the increase of dosage of curcumin(P<0.05),and with the extension of time course(P<0.05).These changes suggested a dose- and time-dependent manner.The proliferation rate of cells also was significantly inhibited(P<0.05). Conclusion:The current results show that the Notch-1 signaling pathway is associated mechanistically with NF-κB activity during curcumin-induced cell growth inhibition and apoptosis of breast cancer cells.These results suggest that the down-regulation of Notch signaling by curcumin may be a novel strategy for the treatment of patients with breast cancer.

  12. Moessbauer and magnetic characterisation of carbon-coated small iron particles

    Energy Technology Data Exchange (ETDEWEB)

    Rechenberg, H.R. E-mail: hercilio@macbeth.if.usp.br; Coaquira, J.A.H.; Marquina, C.; Garcia-Landa, B.; Ibarra, M.R.; Benito, A.M.; Maser, W.; Munoz, E.; Martinez, M.T

    2001-05-01

    Carbon-coated Fe particles have been produced by the Kraetschmer-Huffmann carbon-arc discharge method. Soot, collarette and cathode samples have been separately characterised by Moessbauer spectroscopy and magnetisation measurements in the temperature range 4.2-300 K. From the analysis of the results the content of the different Fe phases and Fe-carbon solid solutions in our samples has been determined, as well as an estimation of particle sizes, which were found to be approximately 9 and 13 nm for the soot and collarette samples, respectively.

  13. EXPERIMENTS AT THE INTERFACE OF CARBON PARTICLE CHEMISTRY AND TOXCIOLOGY

    Science.gov (United States)

    Air pollution includes a complex mixture of carbonaceous gases and particles emitted from multiple anthropogenic, biogenic, and biomass burning sources, and also includes secondary organic components that form during atmospheric aging of these emissions. Exposure to these mixture...

  14. NUDT2 Disruption Elevates Diadenosine Tetraphosphate (Ap4A and Down-Regulates Immune Response and Cancer Promotion Genes.

    Directory of Open Access Journals (Sweden)

    Andrew S Marriott

    Full Text Available Regulation of gene expression is one of several roles proposed for the stress-induced nucleotide diadenosine tetraphosphate (Ap4A. We have examined this directly by a comparative RNA-Seq analysis of KBM-7 chronic myelogenous leukemia cells and KBM-7 cells in which the NUDT2 Ap4A hydrolase gene had been disrupted (NuKO cells, causing a 175-fold increase in intracellular Ap4A. 6,288 differentially expressed genes were identified with P < 0.05. Of these, 980 were up-regulated and 705 down-regulated in NuKO cells with a fold-change ≥ 2. Ingenuity® Pathway Analysis (IPA® was used to assign these genes to known canonical pathways and functional networks. Pathways associated with interferon responses, pattern recognition receptors and inflammation scored highly in the down-regulated set of genes while functions associated with MHC class II antigens were prominent among the up-regulated genes, which otherwise showed little organization into major functional gene sets. Tryptophan catabolism was also strongly down-regulated as were numerous genes known to be involved in tumor promotion in other systems, with roles in the epithelial-mesenchymal transition, proliferation, invasion and metastasis. Conversely, some pro-apoptotic genes were up-regulated. Major upstream factors predicted by IPA® for gene down-regulation included NFκB, STAT1/2, IRF3/4 and SP1 but no major factors controlling gene up-regulation were identified. Potential mechanisms for gene regulation mediated by Ap4A and/or NUDT2 disruption include binding of Ap4A to the HINT1 co-repressor, autocrine activation of purinoceptors by Ap4A, chromatin remodeling, effects of NUDT2 loss on transcript stability, and inhibition of ATP-dependent regulatory factors such as protein kinases by Ap4A. Existing evidence favors the last of these as the most probable mechanism. Regardless, our results suggest that the NUDT2 protein could be a novel cancer chemotherapeutic target, with its inhibition

  15. Down-regulation of POLYGALACTURONASE1 alters firmness, tensile strength and water loss in apple (Malus x domestica) fruit

    OpenAIRE

    Atkinson Ross G; Sutherland Paul W; Johnston Sarah L; Gunaseelan Kularajathevan; Hallett Ian C; Mitra Deepali; Brummell David A; Schröder Roswitha; Johnston Jason W; Schaffer Robert J

    2012-01-01

    Abstract Background While there is now a significant body of research correlating apple (Malus x domestica) fruit softening with the cell wall hydrolase ENDO-POLYGALACTURONASE1 (PG1), there is currently little knowledge of its physiological effects in planta. This study examined the effect of down regulation of PG1 expression in ‘Royal Gala’ apples, a cultivar that typically has high levels of PG1, and softens during fruit ripening. Results PG1-suppressed ‘Royal Gala’ apples harvested from mu...

  16. Dexamethasone Down-Regulates the Expression of microRNA-155 in the Livers of Septic Mice

    OpenAIRE

    Wang, Zhong-hua; Liang, Yan-Bing; Tang, Hao; Chen, Zhi-Bin; Li, Zhen-Yu; Hu, Xu-chu; Ma, Zhong-fu

    2013-01-01

    To investigate the expression of microRNA-155 (miRNA-155) in the livers of mice with lipopolysaccharide (LPS)-induced sepsis and to determine the role of dexamethasone (DXM) in the regulation of miRNA-155 expression, we pretreated mice with or without DXM prior to LPS exposure. Our study demonstrated that the expression of miRNA-155 and inflammatory factors increased in the liver tissues of mice with LPS-induced sepsis and that DXM down-regulated their expression in a dose-dependent manner. M...

  17. Pax6 directly down-regulates Pcsk1n expression thereby regulating PC1/3 dependent proinsulin processing.

    Directory of Open Access Journals (Sweden)

    Ting Liu

    Full Text Available BACKGROUND: Heterozygous paired box6 (Pax6 mutations lead to abnormal glucose metabolism in mice older than 6 months as well as in human beings. Our previous study found that Pax6 deficiency caused down-expression of prohormone convertase 1/3 (Pcsk1, resulting in defective proinsulin processing. As a protein cleaving enzyme, in addition to its expression, the activity of PC1/3 is closely related to its function. We therefore hypothesize that Pax6 mutation alters the activity of PC1/3, which affects proinsulin processing. METHODOLOGY/PRINCIPAL FINDINGS: Using quantitative RT-PCR, western blot and enzyme assay, we found that PC1/3 C-terminal cleavage and its activity were compromised in Pax6 R266Stop mutant mice, and the expression of Pcsk1n, a potent inhibitor of PC1/3, was elevated by Pax6 deficiency in the mutant mice and MIN6 cells. We confirmed the effect of proSAAS, the protein encoded by Pcsk1n, on PC1/3 C-terminal cleavage and its activity by Pcsk1n RNAi in MIN6 cells. Furthermore, by luciferase-reporter analysis, chromatin immunoprecipitation, and electrophoretic mobility shift assay, we revealed that Pax6 bound to Pcsk1n promoter and directly down-regulated its expression. Finally, by co-transfecting Pax6 siRNA with Pcsk1n siRNA, we showed that Pax6 knock-down inhibited proinsulin processing and that this effect could be rescued by proSAAS down-regulation. These findings confirm that Pax6 regulates proinsulin processing partially through proSAAS-mediated PC1/3 processing and activity. CONCLUSIONS/SIGNIFICANCE: Collectively, the above experiments demonstrate that Pax6 can directly down-regulate Pcsk1n expression, which negatively affects PC1/3 C-terminal cleavage and activity and subsequently participates in proinsulin processing. We identified proSAAS as a novel down-regulated target of Pax6 in the regulation of glucose metabolism. This study also provides a complete molecular mechanism for the Pax6 deficiency-caused diabetes.

  18. Ischemic heart disease down-regulates angiotensin type 1 receptor mRNA in human coronary arteries

    DEFF Research Database (Denmark)

    Wackenfors, Angelica; Emilson, Malin; Ingemansson, Richard;

    2004-01-01

    Angiotensin II is important in the development of cardiovascular disease. In the present study, angiotensin II receptor mRNA levels were quantified by real-time polymerase chain reaction (real-time PCR) in human coronary arteries from patients with ischemic heart disease and controls. Furthermore......, the suitability of artery culture for studying angiotensin receptor changes was evaluated by in vitro pharmacology and real-time PCR. The angiotensin type 1 (AT1) receptor mRNA levels were down-regulated in human coronary arteries from patients with ischemic heart disease as compared to controls (P

  19. Both SEPT2 and MLL are down-regulated in MLL-SEPT2 therapy-related myeloid neoplasia

    International Nuclear Information System (INIS)

    A relevant role of septins in leukemogenesis has been uncovered by their involvement as fusion partners in MLL-related leukemia. Recently, we have established the MLL-SEPT2 gene fusion as the molecular abnormality subjacent to the translocation t(2;11)(q37;q23) in therapy-related acute myeloid leukemia. In this work we quantified MLL and SEPT2 gene expression in 58 acute myeloid leukemia patients selected to represent the major AML genetic subgroups, as well as in all three cases of MLL-SEPT2-associated myeloid neoplasms so far described in the literature. Cytogenetics, fluorescence in situ hybridization (FISH) and molecular studies (RT-PCR, qRT-PCR and qMSP) were used to characterize 58 acute myeloid leukemia patients (AML) at diagnosis selected to represent the major AML genetic subgroups: CBFB-MYH11 (n = 13), PML-RARA (n = 12); RUNX1-RUNX1T1 (n = 12), normal karyotype (n = 11), and MLL gene fusions other than MLL-SEPT2 (n = 10). We also studied all three MLL-SEPT2 myeloid neoplasia cases reported in the literature, namely two AML patients and a t-MDS patient. When compared with normal controls, we found a 12.8-fold reduction of wild-type SEPT2 and MLL-SEPT2 combined expression in cases with the MLL-SEPT2 gene fusion (p = 0.007), which is accompanied by a 12.4-fold down-regulation of wild-type MLL and MLL-SEPT2 combined expression (p = 0.028). The down-regulation of SEPT2 in MLL-SEPT2 myeloid neoplasias was statistically significant when compared with all other leukemia genetic subgroups (including those with other MLL gene fusions). In addition, MLL expression was also down-regulated in the group of MLL fusions other than MLL-SEPT2, when compared with the normal control group (p = 0.023) We found a significant down-regulation of both SEPT2 and MLL in MLL-SEPT2 myeloid neoplasias. In addition, we also found that MLL is under-expressed in AML patients with MLL fusions other than MLL-SEPT2

  20. TNF-α-induced down-regulation of CDX2 suppresses MEP1A expression in colitis

    DEFF Research Database (Denmark)

    Coskun, Mehmet; Olsen, Anders Krüger; Holm, Thomas Lindebo;

    2012-01-01

    High levels of pro-inflammatory cytokines are linked to inflammatory bowel disease (IBD). The transcription factor Caudal-related homeobox transcription factor 2 (CDX2) plays a crucial role in differentiation of intestinal epithelium and regulates IBD-susceptibility genes, including meprin 1A (ME......A). The aim was to investigate the expression of CDX2 and MEP1A in colitis; to assess if they are regulated by tumor necrosis factor-α (TNF-α), and finally to reveal if CDX2 is involved in a TNF-α-induced down-regulation of MEP1A....

  1. KCNK5 is Functionally Down-Regulated Upon Long-Term Hypotonicity in Ehrlich Ascites Tumor Cells

    DEFF Research Database (Denmark)

    Kirkegaard, S. S.; Wulff, Tune; Gammeltoft, S.;

    2013-01-01

    Background/Aims: Regulatory volume decrease (RVD) in response to acute cell swelling is well described and KCNK5 (also known as TASK-2 or K2P5.1) has been shown to be the volume sensitive K+ channel in Ehrlich cells. Very little is, on the other hand, known about the effects of long-term hypotoni...... physiological impairment of KCNK5 in Ehrlich cells after long-term hypotonic stimulation is predominantly due to down-regulation of the KCNK5 protein synthesis.© 2013 S. Karger AG, Basel...

  2. MyoD regulates apoptosis of myoblasts through microRNA-mediated down-regulation of Pax3

    OpenAIRE

    Hirai, Hiroyuki; Verma, Mayank; Watanabe, Shuichi; Tastad, Christopher; Asakura, Yoko; Asakura, Atsushi

    2010-01-01

    The molecules that regulate the apoptosis cascade are also involved in differentiation and syncytial fusion in skeletal muscle. MyoD is a myogenic transcription factor that plays essential roles in muscle differentiation. We noticed that MyoD−/− myoblasts display remarkable resistance to apoptosis by down-regulation of miR-1 (microRNA-1) and miR-206 and by up-regulation of Pax3. This resulted in transcriptional activation of antiapoptotic factors Bcl-2 and Bcl-xL. Forced MyoD expression induc...

  3. Down regulation of miR-203 in radiation-induced thymic lymphoma promoted cells proliferation and inhibited apoptosis%Down regulation of miR-203in radiation-induced thymic lymphoma promoted cells proliferation and inhibited apoptosis

    Institute of Scientific and Technical Information of China (English)

    Zhang Chaoxiong; Zhang Mingjian; Gao Fu; Zhou Chuanfeng; Zhang Pei; Cai Jianming; Liu Cong

    2015-01-01

    Objective To investigate the role of miR-203 in radiation-induced thymic lymphoma (RITL).Methods A 60Co irradiator was used for total-body irradiation.MicroRNAs(miRNAs) level was assayed by qRT-PCR.Cell proliferation was assayed by MTT assay.Cell apoptosis was examined by fluorescence activated cell sorter (FACS).Dual luciferase reporter assay system was used to detect the 3'UTR reporter.Results MiR-203 was down-regulated in RITL tissues.Overexpression of miR-203 strongly inhibited the proliferation of both NIH3T3 cells and EL4 cells and vice versa.MiR-203 inhibited cells proliferation and induced apoptosis via TANK-binding kinase (TBK1),SLUG (SNAI2) and Cyclin D1 (CCND1).Conclusions Radiation down-regulated the level of miR-203 in thymic,which promoted radiation-induced thymic lymphoma by targeting TBK1,SNAI2 and CCND1.

  4. Rapid quantification of dimethyl methylphosphonate from activated carbon particles by static headspace gas chromatography mass spectrometry.

    Science.gov (United States)

    Mitchell, Brendan L; Billingsley, Brit G; Logue, Brian A

    2013-06-01

    Activated carbon (AC) particles are utilized as an adsorbent for binding hazardous vapors in protective equipment. The binding affinity and utilization of these AC particles should be known to ensure effective and efficient use. Therefore, a simple and effective method was developed for the quantification of the chemical warfare agent simulant, dimethyl methylphosphonate (DMMP), from AC particles. Static headspace gas chromatography mass-spectrometry with internal standard, DMMP-d6, was used to perform the analysis. The method produced a linear dynamic range of 2.48-620g DMMP/kg carbon and a detection limit of 1.24g DMMP/kg carbon. Furthermore, the method produced a coefficient of variation of less than 16% for all intra- and inter-assay analyses. The method provided a simple and effective procedure for quantifying DMMP from AC particles and was applied to the analysis of a DMMP-exposed AC protective respirator filter.

  5. Fabrication of cast carbon steel with ultrafine TiC particles

    Institute of Scientific and Technical Information of China (English)

    Sang-Hoon LEE; Jin-Ju PARK; Sung-Mo HONG; Byoung-Sun HAN; Min-Ku LEE; Chang-Kyu RHEE

    2011-01-01

    The carbon steels dispersed with ultrafine TiC particles were fabricated by conventional casting method. The casting process is more economical than other available routes for metal matrix composite production, and the large sized components to be fabricated in short processing time. However, it is extremely difficult to obtain uniform dispersion of ultrafine ceramic particles in liquid metals due to the poor wettability and the specific gravity difference between the ceramic particle and metal matrix, In order to solve these problems, the mechanical milling (MM) and surface-active processes were introduced. As a result, Cu coated ultrafine TiC powders made by MM process using high energy ball milling machine were mixed with Sn powders as a surfactant to get better wettability by lowering the surface tension of carbon steel melt, The microstructural investigations by OM show that ultrafine TiC particles are distributed uniformly in carbon steel matrix. The grain sizes of the cast matrix with ultrafine TiC particles are much smaller than those without ultrafine TiC particles. This is probably due to the fact that TiC particles act as nucleation sites during solidification. The wear resistance of cast carbon steel composites added with MMed TiC/Cu-Sn powders is improved due to grain size refinement.

  6. Drinking water biotic safety of particles and bacteria attached to fines in activated carbon process

    Institute of Scientific and Technical Information of China (English)

    CHEN Wei; LIN Tao; WANG Leilei

    2007-01-01

    In this paper,the drinking water biotic safety of particles and bacteria attached to fines in activated carbon process was investigated by actual treatment process and advanced treatment pilot trial with granular activated carbon.In the experiment,the particles were detected by IBR particle calculating instrument,the activated carbon fines were counted on the basis of the most probable number (MPN) with a microscope,the total number of bacteria was analyzed between the conventional agar culture medium and the one with R2A,and the bacteria attached to activated carbon fines was resolved by the homogenization technique.The experimental results showed that the average total number of particles was 205 CNT/mL in the activated carbon effluent during a filter cycle,of which the number of particles with sizes>2μm was 77 CNT/mL more than the present particle control criterion of the American drinking water product standard (50 CNT/mL).The backwash of low density and long duration lowered particle number in the effluent.The MPN of activated carbon frees in the effluent was between 400 and 600 CNT/L,which accounted for less than 5‰ of the total particles from activated carbon filtration for a poor relative level (R2= 0.34).The microorganisms in activated carbon effluent consisted mostly of heterotrophic bacillus and the total bacteria number was five times as high as that of the inflow,i.e.the effluent from sand filter.The actual bacteria number may be truly indicated by the detection technique with R2A culture medium compared with the traditional agar cultivation.The inactivation efficiency of bacteria attached to activated carbon fines was less than 40% under 1.1 mg/L of chlorine contacting for 40 min.Results showed that the particles and bacteria attached to activated carbon fines may influence drinking water biotic safety,and that the effective control measures need to be further investigated.

  7. Influence of carbon black and indium tin oxide absorber particles on laser transmission welding

    Science.gov (United States)

    Aden, Mirko; Mamuschkin, Viktor; Olowinsky, Alexander

    2015-06-01

    For laser transmission welding of polypropylene carbon black and indium tin oxide (ITO) are used as absorber particles. Additionally, the colorant titanium dioxide is mixed to the absorbing part, while the transparent part is kept in natural state. The absorption coefficients of ITO and carbon black particles are obtained, as well as the scattering properties of polypropylene loaded with titanium dioxide (TiO2). At similar concentrations the absorption coefficient of ITO is an order of magnitude smaller than that of carbon black. Simulations of radiation propagation show that the penetration depth of laser light is smaller for carbon black. Therefore, the density of the released heat is higher. Adding TiO2 changes the distribution of heat in case of ITO, whereas for carbon black the effect is negligible. Thermal simulations reveal the influence of the two absorbers and TiO2 on the heat affected zone. The results of the thermal simulations are compared to tensile test results.

  8. Metallic conductivity transition of carbon nanotube yarns coated with silver particles

    International Nuclear Information System (INIS)

    Dry spun carbon nanotube yarns made from vertically aligned multiwalled carbon nanotube forests possess high mechanical strength and behave like semiconductors with electrical conductivity of the order of 4 × 104 S m−1. Coating a submicron-thick film of silver particle-filled polymer on the surface increased the electrical conductivity of the carbon nanotube yarn by 60-fold without significantly sacrificing its mechanical strength. The transitional characteristics of the silver-coated carbon nanotube yarn were investigated by varying the take-up ratio of the silver coating. A step change in conductivity was observed when the silver content in the coated yarn was between 7 and 10 wt% as a result of the formation of connected silver particle networks on the carbon nanotube yarn surface. (papers)

  9. Natural derivatives of curcumin attenuate the Wnt/beta-catenin pathway through down-regulation of the transcriptional coactivator p300.

    Science.gov (United States)

    Ryu, Min-Jung; Cho, Munju; Song, Jie-Young; Yun, Yeon-Sook; Choi, Il-Whan; Kim, Dong-Eun; Park, Byeoung-Soo; Oh, Sangtaek

    2008-12-26

    Curcumin, a component of turmeric (Curcuma longa), has been reported to suppress beta-catenin response transcription (CRT), which is aberrantly activated in colorectal cancer. However, the effects of its natural analogs (demethoxycurcumin [DMC] and bisdemethoxycurcumin [BDMC]) and metabolite (tetrahydrocurcumin [THC]) on the Wnt/beta-catenin pathway have not been investigated. Here, we show that DMC and BDMC suppressed CRT that was activated by Wnt3a conditioned-medium (Wnt3a-CM) without altering the level of intracellular beta-catenin, and inhibited the growth of various colon cancer cells, with comparable potency to curcumin. Additionally, DMC and BDMC down-regulated p300, which is a positive regulator of the Wnt/beta-catenin pathway. Notably, THC also inhibited CRT and cell proliferation, but to a much lesser degree than curcumin, DMC, or BDMC, indicating that the conjugated bonds in the central seven-carbon chain of curcuminoids are essential for the inhibition of Wnt/beta-catenin pathway and the anti-proliferative activity of curcuminoids. Thus, our findings suggest that curcumin derivatives inhibit the Wnt/beta-catenin pathway by decreasing the amount of the transcriptional coactivator p300.

  10. Natural derivatives of curcumin attenuate the Wnt/β-catenin pathway through down-regulation of the transcriptional coactivator p300

    International Nuclear Information System (INIS)

    Curcumin, a component of turmeric (Curcuma longa), has been reported to suppress β-catenin response transcription (CRT), which is aberrantly activated in colorectal cancer. However, the effects of its natural analogs (demethoxycurcumin [DMC] and bisdemethoxycurcumin [BDMC]) and metabolite (tetrahydrocurcumin [THC]) on the Wnt/β-catenin pathway have not been investigated. Here, we show that DMC and BDMC suppressed CRT that was activated by Wnt3a conditioned-medium (Wnt3a-CM) without altering the level of intracellular β-catenin, and inhibited the growth of various colon cancer cells, with comparable potency to curcumin. Additionally, DMC and BDMC down-regulated p300, which is a positive regulator of the Wnt/β-catenin pathway. Notably, THC also inhibited CRT and cell proliferation, but to a much lesser degree than curcumin, DMC, or BDMC, indicating that the conjugated bonds in the central seven-carbon chain of curcuminoids are essential for the inhibition of Wnt/β-catenin pathway and the anti-proliferative activity of curcuminoids. Thus, our findings suggest that curcumin derivatives inhibit the Wnt/β-catenin pathway by decreasing the amount of the transcriptional coactivator p300.

  11. Sost down-regulation by mechanical strain in human osteoblastic cells involves PGE2 signaling via EP4

    OpenAIRE

    Galea, GL; Sunters, A; Meakin, LB; G. Zaman; Sugiyama, T; Lanyon, LE; Price, JS

    2011-01-01

    Sclerostin is a potent inhibitor of bone formation which is down-regulated by mechanical loading. To investigate the mechanisms involved we subjected Saos2 human osteoblastic cells to short periods of dynamic strain and used quantitative reverse transcriptase polymerase chain reaction to compare their responses to unstrained controls. Strain-induced Sost down-regulation was recapitulated by cyclo-oxygenase-2-mediated PGE2, acting through the EP4 receptor, whereas strain-related up-regulation ...

  12. Down-Regulation of Notch-1 Is Associated With Akt and FoxM1 in Inducing Cell Growth Inhibition and Apoptosis in Prostate Cancer Cells

    OpenAIRE

    Wang, Zhiwei; Li, Yiwei; Ahmad, Aamir; Banerjee, Sanjeev; Azmi, Asfar S; Kong, Dejuan; Wojewoda, Christine; Miele, Lucio; Sarkar, Fazlul H

    2011-01-01

    Although many studies have been done to uncover the mechanisms by which down-regulation of Notch-1 exerts its anti-tumor activity against a variety of human malignancies, the precise molecular mechanisms remain unclear. In the present study, we investigated the cellular consequence of Notch-1 down-regulation and also assessed the molecular consequence of Notch-1-mediated alterations of its downstream targets on cell viability and apoptosis in prostate cancer (PCa) cells. We found that the dow...

  13. Neural cell adhesion molecule-180-mediated homophilic binding induces epidermal growth factor receptor (EGFR) down-regulation and uncouples the inhibitory function of EGFR in neurite outgrowth

    DEFF Research Database (Denmark)

    Povlsen, Gro Klitgaard; Berezin, Vladimir; Bock, Elisabeth

    2008-01-01

    The neural cell adhesion molecule (NCAM) plays important roles in neuronal development, regeneration, and synaptic plasticity. NCAM homophilic binding mediates cell adhesion and induces intracellular signals, in which the fibroblast growth factor receptor plays a prominent role. Recent studies on...... this NCAM-180-induced EGFR down-regulation involves increased EGFR ubiquitination and lysosomal EGFR degradation. Furthermore, NCAM-180-mediated EGFR down-regulation requires NCAM homophilic binding and interactions of the cytoplasmic domain of NCAM-180 with intracellular interaction partners, but does...

  14. Heat shock response down-regulates IL-18 expression in the murine macrophage cell line, RAW264.7

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    Heat shock response is a self-defense mechanism for protection of cells and organisms from a wide range of harmful stressors. Recent studies revealed that it is involved in the regulation of cytokines expression. IL-18 is an important cytokine in mediating immune response. We studied LPS-induced IL-18 expression in heat shock treated RAW264.7 murine macrophages. Our results show that the heat shock response significantly inhibited the expression of LPS-induced pro-inflammatory cytokine IL-18. Further research on the down-regulation mechanism shows that this inhibitory effect is correlated to the great suppression of the binding activity of AP-1, which is a transcription factor binding to the promoter of IL-18 (-1120 to -1083) and regulates the transcription of IL-18. Meanwhile, we observed that the phosphorylation of JNK, which is AP-1 upstream kinase, was greatly decreased. These results confirmed that the down-regulation effect on IL-18 production in heat shock response is related to the suppression of the JNK/AP-1 signaling pathway.

  15. MiR-378 Promotes the Migration of Liver Cancer Cells by Down-Regulating Fus Expression

    Directory of Open Access Journals (Sweden)

    Jichun Ma

    2014-12-01

    Full Text Available Background: miR-378 regulates osteoblast differentiation and participates in tumor cell self-renewal and chemo-resistance. However, the function of miR-378 in liver cancer cell migration has not been reported to date. Methods: miR-378 expression was examined using real-time quantitative PCR. HepG2 cell migration and liver cell invasion were examined using wound-healing and cell invasion assays. Additionally, HepG2 cell metastasis was analyzed in nude mice. Results: miR-378 over-expression enhances HepG2 cell proliferation, migration and liver cell invasion. Typical metastatic lesions were found in the livers of mice injected with miR-378-transfected cells, and high levels of the CMV promoter were detected in the nodules, indicating that miR-378 promoted the metastasis of the tumor cells to the liver. We also demonstrated that miR-378 down-regulated Fus expression. Conclusions: Our results suggested that miR-378 enhanced cell migration and metastasis by down-regulating Fus expression.

  16. Labisia pumila extract down-regulates hydroxysteroid (11-beta) dehydrogenase 1 expression and corticosterone levels in ovariectomized rats.

    Science.gov (United States)

    Fazliana, Mansor; Gu, Harvest F; Östenson, Claes-Göran; Yusoff, Mashitah Mohd; Wan Nazaimoon, W M

    2012-04-01

    We evaluated the effects of a standardized Labisia pumila var. alata (LPva) extract on body weight change, hydroxysteroid (11-beta) dehydrogenase 1 (HSD11B1) expressions and corticosterone (CORT) level in ovariectomized (OVX) rats. The decoction of LPva has been used for generations among Malay women in Malaysia to maintain a healthy reproductive system.Thirty-six Sprague-Dawley OVX rats were treated orally with LPva extract (10, 20 or 50 mg/kg/day) or estrogen replacement (ERT) for 30 days. Sham operated rats were used as controls. Compared to untreated OVX rats, LPva-treated rats showed less weight gain and had significantly down-regulated HSD11B1 mRNA in liver tissues. HSD11B1 mRNA in adipose tissues increased by 55% (p rats but normalized in rats treated with LPva. Similarly, there was significant down-regulation (p rats. This is the first study ever conducted to evaluate the beneficial effects of LPva in relation to weight gain caused by estrogen insufficiency. Results implied that the bioactive components in LPva extract affect not only HSD11B1 expressions in both adipose and liver tissues but also decrease circulating CORT. The extract should be explored for its potential use as a natural remedy for weight management. PMID:21833773

  17. Terminal deoxynucleotidyl transferase is down-regulated by AP-1-like regulatory elements in human lymphoid cells.

    Science.gov (United States)

    Peralta-Zaragoza, Oscar; Recillas-Targa, Félix; Madrid-Marina, Vicente

    2004-02-01

    Terminal deoxynucleotidyl transferase (TdT) is a template-independent DNA polymerase that catalyses the incorporation of deoxyribonucleotides into the 3'-hydroxyl end of DNA templates and is thought to increase junctional diversity of antigen receptor genes. TdT is expressed only on immature lymphocytes and acute lymphoblastic leukaemia cells and its transcriptional expression is tightly regulated. We had previously found that protein kinase C (PKC) activation down-regulates TdT expression. PKC-activation induces the synthesis of the Fos and Jun proteins, known as the major components of activation protein 1 (AP-1) transcriptional factor implicated in transcriptional control. Here we report the identification of several DNA-protein interactions within the TdT promoter region in non-TdT expressing human cells. Sequence analysis revealed the presence of a putative AP-1-like DNA-binding site, suggesting that AP-1 may play a relevant role in TdT transcriptional regulation. Using a different source of nuclear extracts and the AP-1-TdT motif as a probe we identified several DNA-protein retarded complexes in electrophoretic mobility shift assays. Super-band shifting analysis using an antibody against c-Jun protein confirmed that the main interaction is produced by a nuclear factor that belongs to the AP-1 family transcription factors. Our findings suggest that the TdT gene expression is down-regulated, at least in part, through AP-1-like transcription factors. PMID:15027905

  18. Overexpression of Insulin Degrading Enzyme could Greatly Contribute to Insulin Down-regulation Induced by Short-Term Swimming Exercise.

    Science.gov (United States)

    Kim, Min Sun; Goo, Jun Seo; Kim, Ji Eun; Nam, So Hee; Choi, Sun Il; Lee, Hye Ryun; Hwang, In Sik; Shim, Sun Bo; Jee, Seung Wan; Lee, Su Hae; Bae, Chang Joon; Cho, Jung Sik; Cho, Jun Yong; Hwang, Dae Youn

    2011-03-01

    Exercise training is highly correlated with the reduced glucose-stimulated insulin secretion (GSIS), although it enhanced insulin sensitivity, glucose uptake and glucose transporter expression to reduce severity of diabetic symptoms. This study investigated the impact of short-term swimming exercise on insulin regulation in the Goto-Kakizaki (GK) rat as a non-obese model of non-insulin-dependent diabetes mellitus. Wistar (W/S) and GK rats were trained 2 hours daily with the swimming exercise for 4 weeks, and then the changes in the metabolism of insulin and glucose were assessed. Body weight was markedly decreased in the exercised GK rats compare to their non-exercised counterpart, while W/S rats did not show any exercise-related changes. Glucose concentration was not changed by exercise, although impaired glucose tolerance was improved in GK rats 120 min after glucose injection. However, insulin concentration was decreased by swimming exercise as in the decrease of GSIS after running exercise. To identify the other cause for exercise-induced insulin down-regulation, the changes in the levels of key factors involved in insulin production (C-peptide) and clearance (insulin-degrading enzyme; IDE) were measured in W/S and GK rats. The C-peptide level was maintained while IDE expression increased markedly. Therefore, these results showed that insulin down-regulation induced by short-term swimming exercise likely attributes to enhanced insulin clearance via IDE over-expression than by altered insulin production.

  19. Down-regulation of plant defence in a resident spider mite species and its effect upon con- and heterospecifics.

    Science.gov (United States)

    Godinho, Diogo P; Janssen, Arne; Dias, Teresa; Cruz, Cristina; Magalhães, Sara

    2016-01-01

    Herbivorous spider mites occurring on tomato plants (Solanum lycopersicum L.) cope with plant defences in various manners: the invasive Tetranychus evansi reduces defences below constitutive levels, whereas several strains of T. urticae induce such defences and others suppress them. In the Mediterranean region, these two species co-occur on tomato plants with T. ludeni, another closely related spider mite species. Unravelling how this third mite species affects plant defences is thus fundamental to understanding the outcome of herbivore interactions in this system. To test the effect of T. ludeni on tomato plant defences, we measured (1) the activity of proteinase inhibitors, indicating the induction of plant defences, in those plants, and (2) mite performance on plants previously infested with each mite species. We show that the performance of T. evansi and T. ludeni on plants previously infested with T. ludeni or T. evansi was better than on clean plants, indicating that these two mite species down-regulate plant defences. We also show that plants attacked by these mite species had lower activity of proteinase inhibitors than clean plants, whereas herbivory by T. urticae increased the activity of these proteins and resulted in reduced spider mite performance. This study thus shows that the property of down-regulation of plant defences below constitutive levels also occurs in T. ludeni.

  20. N-methylhemeanthidine chloride, a novel Amaryllidaceae alkaloid, inhibits pancreatic cancer cell proliferation via down-regulating AKT activation

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Guoli; Yao, Guangmin; Zhan, Guanqun; Hu, Yufeng [Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei PR China (China); Yue, Ming [Hubei Key Laboratory of Drug Target Research and Pharmacodynamic Evaluation, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei (China); Cheng, Ling; Liu, Yaping; Ye, Qi [Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei PR China (China); Qing, Guoliang [Hubei Key Laboratory of Drug Target Research and Pharmacodynamic Evaluation, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei (China); Zhang, Yonghui, E-mail: zhangyh@mails.tjmu.edu.cn [Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei PR China (China); Liu, Hudan, E-mail: hudanliu@hust.edu.cn [Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei PR China (China)

    2014-11-01

    We previously reported the isolation of a novel Amaryllidaceae alkaloid, N-methylhemeanthidine chloride (NMHC), from Zephyranthes candida, which exhibits potent cytotoxicity in a spectrum of tumor cells. However, the mechanism of action remains unclear. Using multiple cell lines derived from human pancreatic cancer, one of the most mortal and refractory human malignancies, we further studied the NMHC-mediated cytotoxicity and found that it induced drastic cytotoxicity in pancreatic cancer cells whereas an insignificant effect on a noncancerous cell line. The NMHC-mediated growth inhibition was more severe than the first-line chemotherapeutic agent gemcitabine, leading to cell cycle arrest, apoptotic death and decreased glycolysis. NMHC exerted its function through down-regulating AKT activation, and the ectopic expression of activated AKT rescued the growth inhibition. Consistently, NMHC injections in a pancreatic cancer xenograft model manifested the anti-tumor effect in vivo. Engrafted tumor cells underwent AKT attenuation and apoptotic death upon treatments. As such, we here demonstrate the AKT inhibition may be one of the mechanisms by which NMHC decreases tumor cell survival rate in vitro and in vivo. Our data thereby suggest that NMHC holds great promise as a potent chemotherapeutic agent against pancreatic cancer and sheds new light on obtaining such agents from natural products toward therapeutic purposes. - Highlights: • N-methylhemeanthidine chloride (NMHC) is a novel Amaryllidaceae alkaloid. • NMHC exhibits potent anti-neoplastic activity. • NMHC leads to cell cycle arrest, apoptotic death and decreased metabolism. • NMHC down-regulates the AKT signaling pathway.

  1. Down-regulation of survivin expression by small interfering RNA induces pancreatic cancer cell apoptosis and enhances its radiosensitivity

    Institute of Scientific and Technical Information of China (English)

    Hai-Tao Guan; Xing-Huan Xue; Zhi-Jun Dai; Xi-Jing Wang; Ang Li; Zhao-Yin Qin

    2006-01-01

    AIM: To investigate the inhibitory effect of small interfering RNA (siRNA) on the expression of survivin in pancreatic cancer cell line PC-2 and the role of siRNA in inducing PC-2 cell apoptosis and enhancing its radiosensitivity.METHODS: A siRNA plasmid expression vector against survivin was constructed and transfected into PC-2 cells with LipofectamineTM 2000. The down regulation of survivin expression was detected by semi-quantitive RT-PCR and immunohistochemical SP method and the role of siRNA in inducing PC-2 cell apoptosis and enhancing its radiosensitivity was detected by flow cytometry.RESULTS: The sequence-specific siRNA efficiently and specifically down-regulated the expression of survivin at both mRNA and protein levels. The expression inhibition ratio was 81.25% at mRNA level detected by semiquantitive RT-PCR and 74.24% at protein level detected by immunohistochemical method. Forty-eight hours after transfection,apoptosis was induced in 7.03% cells by siRNA and in 14.58% cells by siRNA combined with radiation.CONCLUSION: The siRNA plasmid expression vector against survivin can inhibit the expression of survivin in PC-2 cells efficiently and specifically. Inhibiting the expression of survivin can induce apoptosis of PC-2 cells and enhance its radiosensitivity significantly. RNAi against survivin is of potential value in gene tnerapy of pancreatic cancer.

  2. Agitation down-regulates immunoglobulin binding protein EibG expression in Shiga toxin-producing Escherichia coli (STEC.

    Directory of Open Access Journals (Sweden)

    Thorsten Kuczius

    Full Text Available Shiga toxin (Stx-producing Escherichia coli (STEC carrying eibG synthesize Escherichia coli immunoglobulin binding protein (EibG. EibG nonspecifically binds to immunoglobulins and tends to aggregate in multimers but is poorly expressed in wild-type strains. To study synthesis of the proteins and their regulation in the pathogens, we identified natural growth conditions that increased EibG synthesis. EibG proteins as well as corresponding mRNA were highly expressed under static growth conditions while shearing stress created by agitation during growth repressed protein synthesis. Further regulation effects were driven by reduced oxygen tension, and pH up-regulated EibG expression, but to a lesser extent than growth conditions while decreased temperature down-regulated EibG. Bacteria with increased EibG expression during static growth conditions showed a distinct phenotype with chain formation and biofilm generation, which disappeared with motion. High and low EibG expression was reversible indicating a process with up- and down-regulation of the protein expression. Our findings indicate that shear stress represses EibG expression and might reduce bacterial attachments to cells and surfaces.

  3. Endotoxin-induced basal respiration alterations of renal HK-2 cells: A sign of pathologic metabolism down-regulation

    Energy Technology Data Exchange (ETDEWEB)

    Quoilin, C., E-mail: cquoilin@ulg.ac.be [Laboratory of Biomedical Spectroscopy, Department of Physics, University of Liege, 4000 Liege (Belgium); Mouithys-Mickalad, A. [Center of Oxygen Research and Development, Department of Chemistry, University of Liege, 4000 Liege (Belgium); Duranteau, J. [Department of Anaesthesia and Surgical ICU, CHU Bicetre, University Paris XI Sud, 94275 Le Kremlin Bicetre (France); Gallez, B. [Biomedical Magnetic Resonance Group, Louvain Drug Research Institute, Universite catholique de Louvain, 1200 Brussels (Belgium); Hoebeke, M. [Laboratory of Biomedical Spectroscopy, Department of Physics, University of Liege, 4000 Liege (Belgium)

    2012-06-29

    Highlights: Black-Right-Pointing-Pointer A HK-2 cells model of inflammation-induced acute kidney injury. Black-Right-Pointing-Pointer Two oximetry methods: high resolution respirometry and ESR spectroscopy. Black-Right-Pointing-Pointer Oxygen consumption rates of renal cells decrease when treated with LPS. Black-Right-Pointing-Pointer Cells do not recover normal respiration when the LPS treatment is removed. Black-Right-Pointing-Pointer This basal respiration alteration is a sign of pathologic metabolism down-regulation. -- Abstract: To study the mechanism of oxygen regulation in inflammation-induced acute kidney injury, we investigate the effects of a bacterial endotoxin (lipopolysaccharide, LPS) on the basal respiration of proximal tubular epithelial cells (HK-2) both by high-resolution respirometry and electron spin resonance spectroscopy. These two complementary methods have shown that HK-2 cells exhibit a decreased oxygen consumption rate when treated with LPS. Surprisingly, this cellular respiration alteration persists even after the stress factor was removed. We suggested that this irreversible decrease in renal oxygen consumption after LPS challenge is related to a pathologic metabolic down-regulation such as a lack of oxygen utilization by cells.

  4. Endotoxin-induced basal respiration alterations of renal HK-2 cells: A sign of pathologic metabolism down-regulation

    International Nuclear Information System (INIS)

    Highlights: ► A HK-2 cells model of inflammation-induced acute kidney injury. ► Two oximetry methods: high resolution respirometry and ESR spectroscopy. ► Oxygen consumption rates of renal cells decrease when treated with LPS. ► Cells do not recover normal respiration when the LPS treatment is removed. ► This basal respiration alteration is a sign of pathologic metabolism down-regulation. -- Abstract: To study the mechanism of oxygen regulation in inflammation-induced acute kidney injury, we investigate the effects of a bacterial endotoxin (lipopolysaccharide, LPS) on the basal respiration of proximal tubular epithelial cells (HK-2) both by high-resolution respirometry and electron spin resonance spectroscopy. These two complementary methods have shown that HK-2 cells exhibit a decreased oxygen consumption rate when treated with LPS. Surprisingly, this cellular respiration alteration persists even after the stress factor was removed. We suggested that this irreversible decrease in renal oxygen consumption after LPS challenge is related to a pathologic metabolic down-regulation such as a lack of oxygen utilization by cells.

  5. Senescence-related functional nuclear barrier by down-regulation of nucleo-cytoplasmic trafficking gene expression

    International Nuclear Information System (INIS)

    One of the characteristic natures of senescent cells is the hypo- or irresponsiveness not only to growth factors but also to apoptotic stress. In the present study, we confirmed the inhibition of nuclear translocation of activated p-ERK1/2 and NF-kB p50 in response to growth stimuli or LPS in the senescent human diploid fibroblasts. In order to elucidate the underlying mechanism for the senescence-associated hypo-responsiveness, we carried out the comparison study for gene expression profiles through microarray analysis. In consequence, we observed the vast reduction in expression of nucleo-cytoplasmic trafficking genes in senescent cells, when compared with those in young cells. Expression levels of several nucleoporins, karyopherin α, karyopherin β, Ran, and Ran-regulating factors were confirmed to be down-regulated in senescent HDFs by using RT-PCR and Western blot methods. Taken together, these data suggest the operation of certain senescence-associated functional nuclear barriers by down-regulation of the nucleo-cytoplasmic trafficking genes in the senescent cells.

  6. Transient down-regulation of the RNA silencing machinery increases efficiency of Agrobacterium-mediated transformation of Arabidopsis.

    Science.gov (United States)

    Bilichak, Andriy; Yao, Youli; Kovalchuk, Igor

    2014-06-01

    Agrobacterium tumefaciens is a plant pathogen that is widely used in plant transformation. As the process of transgenesis includes the delivery of single-stranded T-DNA molecule, we hypothesized that transformation rate may negatively correlate with the efficiency of the RNA-silencing machinery. Using mutants compromised in either the transcriptional or post-transcriptional gene-silencing pathways, two inhibitors of stable transformation were revealed-AGO2 and NRPD1a. Furthermore, an immunoprecipitation experiment has shown that NRPD1, a subunit of Pol IV, directly interacts with Agrobacterium T-DNA in planta. Using the Tobacco rattle virus (TRV)--based virus-induced gene silencing (VIGS) technique, we demonstrated that the transient down-regulation of the expression of either AGO2 or NRPD1a genes in reproductive organs of Arabidopsis, leads to an increase in transformation rate. We observed a 6.0- and 3.5-fold increase in transformation rate upon transient downregulation of either AGO2 or NRPD1a genes, respectively. This is the first report demonstrating the increase in the plant transformation rate via VIGS-mediated transient down-regulation of the components of epigenetic machinery in reproductive tissue.

  7. Down-regulation of msrb3 and destruction of normal auditory system development through hair cell apoptosis in zebrafish.

    Science.gov (United States)

    Shen, Xiaofang; Liu, Fei; Wang, Yingzhi; Wang, Huijun; Ma, Jing; Xia, Wenjun; Zhang, Jin; Jiang, Nan; Sun, Shaoyang; Wang, Xu; Ma, Duan

    2015-01-01

    Hearing defects can significantly influence quality of life for those who experience them. At this time, 177 deafness genes have been cloned, including 134 non-syndromic hearing-loss genes. The methionine sulfoxide reductase B3 (Ahmed et al., 2011) gene (also called DFNB74) is one such newly discovered hearing-loss gene. Within this gene c.265 T>G and c.55 T>C mutations are associated with autosomal recessive hearing loss. However, the biological role and mechanism underlying how it contributes to deafness is unclear. Thus, to better understand this mutation, we designed splicing morpholinos for the purpose of down-regulating msrb3 in zebrafish. Morphants exhibited small, tiny, fused, or misplaced otoliths and abnormal numbers of otoliths. Down-regulation of msrb3 also caused shorter, thinner, and more crowded cilia. Furthermore, L1-8 neuromasts were reduced and disordered in the lateral line system; hair cells in each neuromast underwent apoptosis. Co-injection with human MSRB3 mRNA partially rescued auditory system defects, but mutant MSRB3 mRNA could not. Thus, msrb3 is instrumental for auditory system development in zebrafish and MSRB3-related deafness may be caused by promotion of hair cell apoptosis.

  8. Stable carbon and radiocarbon isotope compositions of particle size fractions to determine origins of sedimentary organic matter in an estuary

    NARCIS (Netherlands)

    Megens, L; van der Plicht, J; de Leeuw, JW; Smedes, F; Altabet, M.

    2002-01-01

    Stable and radioactive carbon isotopic compositions of particle size fractions of a surface sediment from the Ems-Dollard estuary vary considerably with particle size. The organic material in the fine fractions (

  9. Lung Myofibroblasts Are Characterized by Down-Regulated Cyclooxygenase-2 and Its Main Metabolite, Prostaglandin E2

    Science.gov (United States)

    Gabasa, Marta; Royo, Dolores; Molina-Molina, Maria; Roca-Ferrer, Jordi; Pujols, Laura; Picado, Cesar

    2013-01-01

    Background Prostaglandin E2 (PGE2), the main metabolite of cyclooxygenase (COX), is a well-known anti-fibrotic agent. Moreover, myofibroblasts expressing α-smooth muscle actin (α-SMA), fibroblast expansion and epithelial-mesenchymal transition (EMT) are critical to the pathogenesis of idiopathic pulmonary fibrosis (IPF). Our aim was to investigate the expression of COX-2 and PGE2 in human lung myofibroblasts and establish whether fibroblast-myofibroblast transition (FMT) and EMT are associated with COX-2 and PGE2 down-regulation. Methods Fibroblasts obtained from IPF patients (n = 6) and patients undergoing spontaneous pneumothorax (control, n = 6) and alveolar epithelial cell line A549 were incubated with TGF-β1 and FMT and EMT markers were evaluated. COX-2 and α-SMA expression, PGE2 secretion and cell proliferation were measured after IL-1β and PGE2 incubation. Results Myofibroblasts from both control and IPF fibroblast cultures stimulated with IL-1β showed no COX-2 expression. IPF fibroblasts showed increased myofibroblast population and reduced COX-2 expression in response to IL-1β. TGF-β1 increased the number of myofibroblasts in a time-dependent manner. In contrast, TGF-β1 induced slight COX-2 expression at 4 h (without increase in myofibroblasts) and 24 h, but not at 72 h. Both IPF and control cultures incubated with TGF-β1 for 72 h showed diminished COX-2 induction, PGE2 secretion and α-SMA expression after IL-1β addition. The latter decreased proliferation in fibroblasts but not in myofibroblasts. A549 cells incubated with TGF-β1 for 72 h showed down-regulated COX-2 expression and low basal PGE2 secretion in response to IL-1β. Immuno-histochemical analysis of IPF lung tissue showed no COX-2 immuno-reactivity in myofibroblast foci. Conclusions Myofibroblasts are associated with COX-2 down-regulation and reduced PGE2 production, which could be crucial in IPF development and progression. PMID:23755232

  10. Penetration and distribution of carbon particles in a teleost fish, Poecilia formosa (Girard), the Amazon molly

    Energy Technology Data Exchange (ETDEWEB)

    Woodhead, A.D.

    1981-01-01

    Data is given on the tissue distribution of carbon particles in Amazon mollies exposed for periods of 24-120 h to a 0-0.05% suspension. Very little carbon penetrated the body, either by way of the intestine or the gills. The little amount that entered appeared to pass almost exclusively through the posterior intestine. There was no anatomical specialization of the cells in this area equivalent to Peyer's patches in the intestine of mammals. We suggest that the uptake in the posterior intestine is related to its greater surface area and possibly to some enhanced mobility. After intraperitoneal (ip) injection, carbon that entered the body accumulated at three sites: the heart, the mesentery and, especially, in the head kidney. By 120 h large accumulations were seen in the intertubular areas of the kidney; there was no evidence of excretion of carbon particles from these areas. (JMT)

  11. Preparation and characterization of mesoporous hybrid particle-fiber carbon monoliths

    Energy Technology Data Exchange (ETDEWEB)

    Fuertes, A.B.; Marban, G. [Inst. Nacional del Carbon (CSIC), Oviedo (Spain); Nevskaia, D.M. [Universidad Nacional de Educacion a Distancia (UNED), Madrid (Spain). Facultad de Ciencas, Dept. de Quimica Inorganica y Tecnica

    2002-05-01

    Porous carbon materials are a subject of increasing attention in many areas of technology such as air purification, catalysis, refrigeration, gas and energy storage, and energy production. Superactivated carbons (SAC) are powdered activated carbons generally made from mesocarbon microbeads and have a very high adsorption capacity. They are highly appropriate for use in evaporative loss control devices (automobile canisters), catalytic supports, fuel-cell electrodes, and double-layer electrical capacitors. In all of these applications it is desirable that the carbon particles be immobilized in order to form rigid devices of high permeability. This communication describes a method to immobilize these fine particles in order to obtain rigid structures with a high internal porosity. (orig.)

  12. Effect of sulfate and carbonate minerals on particle-size distributions in arid soils

    Science.gov (United States)

    Goossens, Dirk; Buck, Brenda J.; Teng, Yuazxin; Robins, Colin; Goldstein, Harland L.

    2014-01-01

    Arid soils pose unique problems during measurement and interpretation of particle-size distributions (PSDs) because they often contain high concentrations of water-soluble salts. This study investigates the effects of sulfate and carbonate minerals on grain-size analysis by comparing analyses in water, in which the minerals dissolve, and isopropanol (IPA), in which they do not. The presence of gypsum, in particular, substantially affects particle-size analysis once the concentration of gypsum in the sample exceeds the mineral’s solubility threshold. For smaller concentrations particle-size results are unaffected. This is because at concentrations above the solubility threshold fine particles cement together or bind to coarser particles or aggregates already present in the sample, or soluble mineral coatings enlarge grains. Formation of discrete crystallites exacerbates the problem. When soluble minerals are dissolved the original, insoluble grains will become partly or entirely liberated. Thus, removing soluble minerals will result in an increase in measured fine particles. Distortion of particle-size analysis is larger for sulfate minerals than for carbonate minerals because of the much higher solubility in water of the former. When possible, arid soils should be analyzed using a liquid in which the mineral grains do not dissolve, such as IPA, because the results will more accurately reflect the PSD under most arid soil field conditions. This is especially important when interpreting soil and environmental processes affected by particle size.

  13. Method of evaluating the integrity of the outer carbon layer of triso-coated reactor fuel particles

    Energy Technology Data Exchange (ETDEWEB)

    Caputo, Anthony J. (Knoxville, TN); Costanzo, Dante A. (Oak Ridge, TN); Lackey, Jr., Walter J. (Oak Ridge, TN); Layton, Frank L. (Clinton, TN); Stinton, David P. (Knoxville, TN)

    1980-01-01

    This invention relates to a method for determining defective final layers of carbon on triso-coated fuel particles and the like. Samples of the particles are subjected to a high temperature treatment with gaseous chlorine and thereafter radiographed. The chlorine penetrates through any defective carbon layer and reacts with the underlying silicon carbide resulting in the volatilization of the silicon as SiCl.sub.4 leaving carbon as a porous layer. This porous carbon layer is easily detected by the radiography.

  14. Method of evaluating the integrity of the outer carbon layer of triso-coated reactor fuel particles

    Energy Technology Data Exchange (ETDEWEB)

    Caputo, A.J.; Costanzo, D.A.; Lackey, W.J.; Layton, F.L.; Stinton, D.P.

    1980-10-07

    This invention relates to a method for determining defective final layers of carbon on triso-coated fuel particles and the like. Samples of the particles are subjected to a high temperature treatment with gaseous chlorine and thereafter radiographed. The chlorine penetrates through any defective carbon layer and reacts with the underlying silicon carbide resulting in the volatilization of the silicon as sicl4 leaving carbon as a porous layer. This porous carbon layer is easily detected by the radiography.

  15. Growth dynamics of carbon-metal particles and nanotubes synthesized by CO2 laser vaporization

    Science.gov (United States)

    Kokai, F.; Takahashi, K.; Yudasaka, M.; Iijima, S.

    To study the growth of carbon-Co/Ni particles and single-wall carbon nanotubes (SWNTs) by 20 ms CO2 laser-pulse irradiation of a graphite-Co/Ni (1.2 at.%) target in an Ar gas atmosphere (600 Torr), we used emission imaging spectroscopy and shadowgraphy with a temporal resolution of 1.67 ms. Wavelength-selected emission images showed that C2 emission was strong in the region close to the target (within 2 cm), while for the same region the blackbody radiation from the large clusters or particles increased with increasing distance from the target. Shadowgraph images showed that the viscous flow of carbon and metal species formed a mushroom or a turbulent cloud spreading slowly into the Ar atmosphere, indicating that particles and SWNTs continued to grow as the ejected material cooled. In addition, emission imaging spectroscopy at 1200 °C showed that C2 and hot clusters and particles with higher emission intensities were distributed over much wider areas. We discuss the growth dynamics of the particles and SWNTs through the interaction of the ambient Ar with the carbon and metal species released from the target by the laser pulse.

  16. Microbeam analysis of four chondritic interplanetary dust particles for major elements, carbon and oxygen

    Science.gov (United States)

    Blanford, G. E.; Thomas, K. L.; Mckay, D. S.

    1988-01-01

    Chemical compositions determined using electron excited X-rays are reported for four interplanetary dust particles collected in the stratosphere. These analyses include measurements of carbon and oxygen abundances which are important elements in these primitive materials. Spot analyses show very heterogeneous compositions on a micrometer scale although average composition approaches that of C1 carbonaceous chondrites. While the spot analyses show intermediate compositions between cometary dust and carbonaceous chondrites, the heterogeneity more closely resembles that of comet Halley dust particles.

  17. Worker exposure to ultrafine particles during carbon black treatment

    OpenAIRE

    Urszula Mikołajczyk; Stella Bujak-Pietrek; Irena Szadkowska-Stańczyk

    2015-01-01

    Wstęp: Celem badania była ocena uwalniania do powietrza stanowisk pracy cząstek ultradrobnych podczas przesypu i pakowania sadzy technicznej. Materiał i metody: Ocena obejmowała wyniki pomiarów przeprowadzonych w zakładzie przesypu sadzy technicznej przed rozpoczęciem procesu przesypu, w czasie wykonywania i po zakończeniu procesu. Określono stężenie liczbowe cząstek o wymiarach z zakresu 10–1000 nm i 10–100 nm z wykorzystaniem kondensacyjnego licznika cząstek (condensation particle cou...

  18. Nucleolin down-regulation is involved in ADP-induced cell cycle arrest in S phase and cell apoptosis in vascular endothelial cells.

    Directory of Open Access Journals (Sweden)

    Wenmeng Wang

    Full Text Available High concentration of extracellular ADP has been reported to induce cell apoptosis, but the molecular mechanisms remain not fully elucidated. In this study, we found by serendipity that ADP treatment of human umbilical vein endothelial cells (HUVEC and human aortic endothelial cells (HAEC down-regulated the protein level of nucleolin in a dose- and time-dependent manner. ADP treatment did not decrease the transcript level of nucloelin, suggesting that ADP might induce nucleolin protein degradation. HUVEC and HAEC expressed ADP receptor P2Y13 receptor, but did not express P2Y1 or P2Y12 receptors. However, P2Y1, 12, 13 receptor antagonists MRS2179, PSB0739, MRS2211 did not inhibit ADP-induced down-regulation of nucleolin. Moreover, MRS2211 itself down-regulated nucleolin protein level. In addition, 2-MeSADP, an agonist for P2Y1, 12 and 13 receptors, did not down-regulate nucleolin protein. These results suggested that ADP-induced nucleolin down-regulation was not due to the activation of P2Y1, 12, or 13 receptors. We also found that ADP treatment induced cell cycle arrest in S phase, cell apoptosis and cell proliferation inhibition via nucleolin down-regulation. The over-expression of nucleolin by gene transfer partly reversed ADP-induced cell cycle arrest, cell apoptosis and cell proliferation inhibition. Furthermore, ADP sensitized HUVEC to cisplatin-induced cell death by the down-regulation of Bcl-2 expression. Taken together, we found, for the first time to our knowledge, a novel mechanism by which ADP regulates cell proliferation by induction of cell cycle arrest and cell apoptosis via targeting nucelolin.

  19. Biological properties of different type carbon particles in vitro study on primary culture of endothelial cells.

    Science.gov (United States)

    Czerniak-Reczulska, M; Niedzielski, P; Balcerczyk, A; Bartosz, G; Karowicz-Bilińska, A; Mitura, K

    2010-02-01

    Carbon powders have extended surface of carbon layers, which is of significant biomedical importance since the powders are employed to cover implants material. Carbon Powder Particles are produced by different methods: by a detonation method, by RF PACVD (Radio Frequency Plasma Activated Chemical Vapour Deposition) or MW/RF PCVD (Microwave/Radio Frequency Plasma Activated Chemical Vapour Deposition) and others. Our previous data showed that Carbon Powder Particles may act as antioxidant and/or anti-inflammatory factor. However the mechanism of such behavior has been not fully understood. The aim of the work was tested influence carbon powders manufactured by Radio Frequency Plasma Activated Chemical Vapour Deposition RFPACVD method and detonation method on selected parameters of human endothelial cells, which play a crucial role in the regulation of the circulation and vascular wall homeostasis. Graphite powder was used as a control substance. Endothelial cells are actively involved in a wide variety of processes e.g., inflammatory responses to a different type of stimuli (ILs, TNF-alpha) or regulating vasomotor tone via production of vasorelaxants and vasocontrictors. Biological activation is dependent on the type and quantity of chemical bonds on the surface of the powders. The effect of powders on the proliferation of HUVECs (Human Umbilical Vein Endothelial Cells) was determined by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) reduction assay. We found decreased cell proliferation after 72 h treatment with graphite as well as Carbon Powder Particles. PMID:20352757

  20. Niemann-Pick C1 like 1 gene expression is down-regulated by LXR activators in the intestine

    International Nuclear Information System (INIS)

    Niemann-Pick C1 like 1 (NPC1L1) is a protein critical for intestinal cholesterol absorption. The nuclear receptors peroxisome proliferator-activated receptor alpha (PPARα) and liver X receptors (LXRα and LXRβ) are major regulators of cholesterol homeostasis and their activation results in a reduced absorption of intestinal cholesterol. The goal of this study was to define the role of PPARα and LXR nuclear receptors in the regulation of NPC1L1 gene expression. We show that LXR activators down-regulate NPC1L1 mRNA levels in the human enterocyte cell line Caco-2/TC7, whereas PPARα ligands have no effect. Furthermore, NPC1L1 mRNA levels are decreased in vivo, in duodenum of mice treated with the LXR agonist T0901317. In conclusion, the present study identifies NPC1L1 as a novel LXR target gene further supporting a crucial role of LXR in intestinal cholesterol homeostasis

  1. Down-regulated expression of NPM1 in IMS-M2 cell line by (-)-epigallocatechin-3-gallate

    Institute of Scientific and Technical Information of China (English)

    Hoang Thanh Chi; Bui Thi Kim Ly; Hoang Anh Vu; Yuko Sato; Phu Chi Dung; Phan Thi Xinh

    2014-01-01

    Objective: To investigate the inhibited effect of epigallocatechin-3-gallate (EGCG) on the expression of NPM1 in IMS-M2 cells harboring the NPM1 mutations.Methods:Cell proliferation assay was performed to test the effects of EGCG on cell growth of IMS-M2 cells harboring the NPM1 mutations. Western blot analysis were performed to test the protein expression of NPM1, AKT, those associated with apoptosis. Results: EGCG can down-regulate the expression of NPM1 in IMS-M2 cells harboring the NPM1 mutations. Moreover, EGCG also suppressed the cell proliferation and induced apoptosis in IMS-M2 cells.Conclusions:The results suggested that EGCG could be considered as a reagent for treatment of AML patients with NPM1 mutations.

  2. Down-regulation of the chemokine receptor CCR5 by activation of chemotactic formyl peptide receptor in human monocytes.

    Science.gov (United States)

    Shen, W; Li, B; Wetzel, M A; Rogers, T J; Henderson, E E; Su, S B; Gong, W; Le, Y; Sargeant, R; Dimitrov, D S; Oppenheim, J J; Wang, J M

    2000-10-15

    Interactions between cell surface receptors are important regulatory elements in the complex host responses to infections. In this study, it is shown that a classic chemotactic factor, the bacterial chemotactic peptide N-formyl-methionyl-leucylphenyl-alanine (fMLF), rapidly induced a protein-kinase-C-mediated serine phosphorylation and down-regulation of the chemokine receptor CCR5, which serves as a major human immunodeficiency virus (HIV)-1 coreceptor. The fMLF binding to its receptor, formyl peptide receptor (FPR), resulted in significant attenuation of cell responses to CCR5 ligands and in inhibition of HIV-1-envelope-glycoprotein-mediated fusion and infection of cells expressing CD4, CCR5, and FPR. The finding that the expression and function of CCR5 can be regulated by peptides that use an unrelated receptor may provide a novel approach to the design of anti-inflamatory and antiretroviral agents. (Blood. 2000;96:2887-2894)

  3. MicroRNA 135a suppresses lymph node metastasis through down-regulation of ROCK1 in early gastric cancer.

    Directory of Open Access Journals (Sweden)

    Ji-Young Shin

    Full Text Available MicroRNAs (miRNAs play a critical role in gastric cancer progression and metastasis. This study investigated the role of miRNA-135a in early gastric cancer (EGC including lymph node (LN metastasis. We examined the correlation between miRNA-135a expression and clinical outcomes in 59 patients who underwent surgery for EGC. Using gastric cancer cell lines, we performed functional and target gene analyses. miRNA-135a expression was down-regulated in 33.9% of patients. These patients showed a significantly more advanced stage (TNM stage ≥ IB, 35.0% vs. 12.8%, p = 0.045 and higher rate of LN metastasis (30.0% vs. 5.1%, p = 0.014 than those with up-regulation of miRNA-135a expression. In a multivariate analysis, down-regulation of miRNA-135a was an independent risk factor for LN metastasis (adjusted odds ratio, 8.04; 95% confidence interval, 1.08-59.81; p = 0.042. Functional analyses using gastric cancer cell lines showed that miRNA-135a suppressed cell viability, epithelial-mesenchymal transition, cell invasion, and migration. ROCK1 was a target of miRNA-135a and its expression was inversely correlated to that of miRNA-135a. ROCK1 expression was significantly increased in EGC patients with LN metastasis than in those without LN metastasis. Our results confirm the tumor-suppressive role of miRNA-135a, and demonstrate its role in LN metastasis in EGC. miRNA-135a and its target gene ROCK1 may be novel therapeutic and prognostic targets for EGC.

  4. miR-200c Inhibits Melanoma Progression and Drug Resistance through Down-Regulation of Bmi-1

    Science.gov (United States)

    Liu, Shujing; Tetzlaff, Michael T.; Cui, Rutao; Xu, Xiaowei

    2013-01-01

    MicroRNAs (miRNAs) are short noncoding RNAs that play crucial roles in tumorigenesis and tumor progression. Melanoma is the most aggressive skin cancer that is resistant or rapidly develops resistance to a variety of chemotherapeutic agents. The role of miRNAs in melanoma progression and drug resistance has not been well studied. Herein, we demonstrate that miR-200c is down-regulated in melanomas (primary and metastatic) compared with melanocytic nevi. Overexpression of miR-200c in melanoma cells resulted in significantly decreased cell proliferation and migratory capacity as well as drug resistance. miR-200c overexpression resulted in significant down-regulation of BMI-1, ABCG2, ABCG5, and MDR1 expression and in a concomitant increase in E-cadherin levels. Knockdown of BMI-1 showed similar effects as miR-200c overexpression in melanoma cells. In addition, miR-200c overexpression significantly inhibited melanoma xenograft growth and metastasis in vivo, and this correlated with diminished expression of BMI-1 and reduced levels of E-cadherin in these tumors. The effects of miR-200c on melanoma cell proliferation and migratory capacity and on self-renewal were rescued by overexpression of Bmi-1, and the reversal of these phenotypes correlated with a reduction in E-cadherin expression and increased levels of ABCG2, ABCG5, and MDR1. Taken together, these findings demonstrate a key role for miR-200c in melanoma progression and drug resistance. These results suggest that miR-200c may represent a critical target for increasing melanoma sensitivity to clinical therapies. PMID:22982443

  5. MicroRNA expression is down-regulated and reorganized in prefrontal cortex of depressed suicide subjects.

    Directory of Open Access Journals (Sweden)

    Neil R Smalheiser

    Full Text Available BACKGROUND: Recent studies suggest that alterations in expression of genes, including those which regulate neural and structural plasticity, may be crucial in the pathogenesis of depression. MicroRNAs (miRNAs are newly discovered regulators of gene expression that have recently been implicated in a variety of human diseases, including neuropsychiatric diseases. METHODOLOGY/PRINCIPAL FINDINGS: The present study was undertaken to examine whether the miRNA network is altered in the brain of depressed suicide subjects. Expression of miRNAs was measured in prefrontal cortex (Brodmann Area 9 of antidepressant-free depressed suicide (n = 18 and well-matched non-psychiatric control subjects (n = 17 using multiplex RT-PCR plates. We found that overall miRNA expression was significantly and globally down-regulated in prefrontal cortex of depressed suicide subjects. Using individual tests of statistical significance, 21 miRNAs were significantly decreased at p = 0.05 or better. Many of the down-regulated miRNAs were encoded at nearby chromosomal loci, shared motifs within the 5'-seeds, and shared putative mRNA targets, several of which have been implicated in depression. In addition, a set of 29 miRNAs, whose expression was not pairwise correlated in the normal controls, showed a high degree of co-regulation across individuals in the depressed suicide group. CONCLUSIONS/SIGNIFICANCE: The findings show widespread changes in miRNA expression that are likely to participate in pathogenesis of major depression and/or suicide. Further studies are needed to identify whether the miRNA changes lead to altered expression of prefrontal cortex mRNAs, either directly (by acting as miRNA targets or indirectly (e.g., by affecting transcription factors.

  6. Histone deacetylase 1 (HDAC1) participates in the down-regulation of corticotropin releasing hormone gene (crh) expression.

    Science.gov (United States)

    Miller, Lydia; Foradori, Chad D; Lalmansingh, Avin S; Sharma, Dharmendra; Handa, Robert J; Uht, Rosalie M

    2011-08-01

    The paraventricular nucleus of the hypothalamus (PVH) plays a central role in regulating the hypothalamic-pituitary-adrenal (HPA) axis. Medial parvocellular neurons of the PVH (mpPVH) integrate sensory and humoral inputs to maintain homeostasis. Humoral inputs include glucocorticoids secreted by the adrenals, which down-regulate HPA activation. A primary glucocorticoid target is the population of mpPVH neurons that synthesize and secrete corticotropin-releasing factors, the most potent of which is corticotropin-releasing hormone (CRH). Although CRH gene (crh) expression is known to be down-regulated by glucocorticoids, the mechanisms by which this process occurs are still poorly understood. To begin this study we postulated that glucocorticoid repression of crh involves HDAC recruitment to the region of the crh proximal promoter. To evaluate this hypothesis, we treated hypothalamic cells that express CRH with the HDAC inhibitor trichostatin A (TSA). As predicted, treatment with TSA led to increased CRH mRNA levels and crh promoter activity. Although co-treatment with Dex (10(-7)M) reduced the TSA effect on mRNA levels, it failed to reduce promoter activity; however co-transfection of HDAC1 but not 3 restored Dex inhibition. A distinction between HDAC1 and 3 was also apparent with respect to crh promoter occupancy. Dex led to increased HDAC1 but not HDAC3 occupancy. In vivo studies revealed that CRH-immunoreactive (-ir) neurons contained HDAC1- and HDAC3-ir. Collectively, these data point to a role for HDAC1 in the physiologic regulation of crh. PMID:21463644

  7. miR-125b suppresses the proliferation and migration of osteosarcoma cells through down-regulation of STAT3

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Li-hong; Li, Hui; Li, Jin-ping; Zhong, Hui; Zhang, Han-chon; Chen, Jia [Department of Orthopedics, The Second Xiangya Hospital of Central South University, Changsha 410010 (China); Xiao, Tao, E-mail: xiaotaoxyl@163.com [Department of Orthopedics, The Second Xiangya Hospital of Central South University, Changsha 410010 (China)

    2011-12-09

    Highlights: Black-Right-Pointing-Pointer miR-125b is frequently down-regulated in osteosarcoma samples and human osteosarcoma cell lines. Black-Right-Pointing-Pointer Ectopic restoration of miR-125b suppresses cell proliferation and migration in vitro. Black-Right-Pointing-Pointer STAT3 is the direct and functional downstream target of miR-125b. Black-Right-Pointing-Pointer STAT3 can bind to the promoter region of miR-125b and serves as a transactivator. -- Abstract: There is accumulating evidence that microRNAs are involved in multiple processes in development and tumor progression. Abnormally expressed miR-125b was found to play a fundamental role in several types of cancer; however, whether miR-125b participates in regulating the initiation and progress of osteosarcoma still remains unclear. Here we demonstrate that miR-125b is frequently down-regulated in osteosarcoma samples and human osteosarcoma cell lines. The ectopic restoration of miR-125b expression in human osteosarcoma cells suppresses proliferation and migration in vitro and inhibits tumor formation in vivo. We further identified signal transducer and activator of transcription 3 (STAT3) as the direct and functional downstream target of miR-125b. Interestingly, we discovered that the expression of miR-125b is regulated by STAT3 at the level of transcription. STAT3 binds to the promoter region of miR-125b in vitro and serves as a transactivator. Taken together, our findings point to an important role in the molecular etiology of osteosarcoma and suggest that miR-125b is a potential target in the treatment of osteosarcoma.

  8. HPV16 E2 could act as down-regulator in cellular genes implicated in apoptosis, proliferation and cell differentiation

    Directory of Open Access Journals (Sweden)

    Valencia-Hernández Armando

    2011-05-01

    Full Text Available Abstract Background Human Papillomavirus (HPV E2 plays several important roles in the viral cycle, including the transcriptional regulation of the oncogenes E6 and E7, the regulation of the viral genome replication by its association with E1 helicase and participates in the viral genome segregation during mitosis by its association with the cellular protein Brd4. It has been shown that E2 protein can regulate negative or positively the activity of several cellular promoters, although the precise mechanism of this regulation is uncertain. In this work we constructed a recombinant adenoviral vector to overexpress HPV16 E2 and evaluated the global pattern of biological processes regulated by E2 using microarrays expression analysis. Results The gene expression profile was strongly modified in cells expressing HPV16 E2, finding 1048 down-regulated genes, and 581 up-regulated. The main cellular pathway modified was WNT since we found 28 genes down-regulated and 15 up-regulated. Interestingly, this pathway is a convergence point for regulating the expression of genes involved in several cellular processes, including apoptosis, proliferation and cell differentiation; MYCN, JAG1 and MAPK13 genes were selected to validate by RT-qPCR the microarray data as these genes in an altered level of expression, modify very important cellular processes. Additionally, we found that a large number of genes from pathways such as PDGF, angiogenesis and cytokines and chemokines mediated inflammation, were also modified in their expression. Conclusions Our results demonstrate that HPV16 E2 has regulatory effects on cellular gene expression in HPV negative cells, independent of the other HPV proteins, and the gene profile observed indicates that these effects could be mediated by interactions with cellular proteins. The cellular processes affected suggest that E2 expression leads to the cells in to a convenient environment for a replicative cycle of the virus.

  9. Shoot-Specific Down-Regulation of Protein Farnesyltransferase (α-Subunit) for Yield Protection against Drought in Canola

    Institute of Scientific and Technical Information of China (English)

    Yang Wang; Michelle Beaith; Maryse Chalifoux; Jifeng Ying; Tina Uchacz; Carlene Sarvas; Rebecca Griffiths; Monika Kuzma; Jiangxin Wan; Yafan Huang

    2009-01-01

    Canola (Brassica napus L.) is one of the most important oilseed crops in the world and its seed yield and quality are significantly affected by drought stress. As an innate and adaptive response to water deficit, land plants avoid potential damage by rapid biosynthesis of the phytohormone abscisic acid (ABA), which triggers stomatal closure to reduce transpirational water loss. The ABA-mediated stomatal response is a dosage-dependent process; thus, one genetic engineering approach for achieving drought avoidance could be to sensitize the guard cell's responsiveness to this hormone.Recent genetic studies have pinpointed protein farnesyltransferase as a key negative regulator controlling ABA sensitivity in the guard cells. We have previously shown that down-regulation of the gene encoding Arabidopsis β-subunit of farnesyltransferase (ERA1) enhances the plant's sensitivity to ABA and drought tolerance. Although the α-subunit of famesyltransferase (AtFTA) is also implicated in ABA sensing, the effectiveness of using such a gene target for improving drought tolerance in a crop plant has not been validated. Here, we report the identification and characterization of the promoter of Arabidopsis hydroxypyruvate reductase (AtHPR1), which expresses specifically in the shoot and not in non-photosynthetic tissues such as root. The promoter region of AtHPR1 contains the core motif of the well characterized dehydration-responsive cis-acting element and we have confirmed that AtHPR1 expression is inducible by drought stress. Conditional and specific down-regulation of FTA in canola using the AtHPR1 promoter driving an RNAi construct resulted in yield protection against drought stress in the field. Using this molecular strategy, we have made significant progress in engineering drought tolerance in this important crop species.

  10. Triptolide inhibits the proliferation of prostate cancer cells and down-regulates SUMO-specific protease 1 expression.

    Directory of Open Access Journals (Sweden)

    Weiwei Huang

    Full Text Available Recently, traditional Chinese medicine and medicinal herbs have attracted more attentions worldwide for its anti-tumor efficacy. Celastrol and Triptolide, two active components extracted from the Chinese herb Tripterygium wilfordii Hook F (known as Lei Gong Teng or Thunder of God Vine, have shown anti-tumor effects. Celastrol was identified as a natural 26 s proteasome inhibitor which promotes cell apoptosis and inhibits tumor growth. The effect and mechanism of Triptolide on prostate cancer (PCa is not well studied. Here we demonstrated that Triptolide, more potent than Celastrol, inhibited cell growth and induced cell death in LNCaP and PC-3 cell lines. Triptolide also significantly inhibited the xenografted PC-3 tumor growth in nude mice. Moreover, Triptolide induced PCa cell apoptosis through caspases activation and PARP cleavage. Unbalance between SUMOylation and deSUMOylation was reported to play an important role in PCa progression. SUMO-specific protease 1 (SENP1 was thought to be a potential marker and therapeutical target of PCa. Importantly, we observed that Triptolide down-regulated SENP1 expression in both mRNA and protein levels in dose-dependent and time-dependent manners, resulting in an enhanced cellular SUMOylation in PCa cells. Meanwhile, Triptolide decreased AR and c-Jun expression at similar manners, and suppressed AR and c-Jun transcription activity. Furthermore, knockdown or ectopic SENP1, c-Jun and AR expression in PCa cells inhibited the Triptolide anti-PCa effects. Taken together, our data suggest that Triptolide is a natural compound with potential therapeutic value for PCa. Its anti-tumor activity may be attributed to mechanisms involving down-regulation of SENP1 that restores SUMOylation and deSUMOyaltion balance and negative regulation of AR and c-Jun expression that inhibits the AR and c-Jun mediated transcription in PCa.

  11. The Cell Surface Estrogen Receptor, G Protein- Coupled Receptor 30 (GPR30, is Markedly Down Regulated During Breast Tumorigenesis

    Directory of Open Access Journals (Sweden)

    Indira Poola

    2008-01-01

    Full Text Available Background: GPR30 is a cell surface estrogen receptor that has been shown to mediate a number of non-genomic rapid effects of estrogen and appear to balance the signaling of estrogen and growth factors. In addition, progestins appear to use GPR30 for their actions. Therefore, GPR30 could play a critical role in hormonal regulation of breast epithelial cell integrity. Deregulation of the events mediated by GPR30 could contribute to tumorigenesis.Methods: To understand the role of GPR30 in the deregulation of estrogen signaling processes during breast carcinogenesis, we have undertaken this study to investigate its expression at mRNA levels in tumor tissues and their matched normal tissues. We compared its expression at mRNA levels by RT quantitative real-time PCR relative to GAPDH in ERα”—positive (n = 54 and ERα”—negative (n = 45 breast cancer tissues to their matched normal tissues.Results: We report here, for the first time, that GPR30 mRNA levels were significantly down-regulated in cancer tissues in comparison with their matched normal tissues (p 0.0001 by two sided paired t-test. The GPR30 expression levels were significantly lower in tumor tissues from patients (n = 29 who had lymph node metastasis in comparison with tumors from patients (n = 53 who were negative for lymph node metastasis (two sample t-test, p 0.02, but no association was found with ERα, PR and other tumor characteristics.Conclusions: Down-regulation of GPR30 could contribute to breast tumorigenesis and lymph node metastasis.

  12. Pamidronate Down-regulates Tumor Necrosis Factor-alpha Induced Matrix Metalloproteinases Expression in Human Intervertebral Disc Cells

    Science.gov (United States)

    Kang, Young-Mi; Hong, Seong-Hwan; Yang, Jae-Ho; Oh, Jin-Cheol; Park, Jin-Oh; Lee, Byung Ho; Lee, Sang-Yoon; Kim, Hak-Sun; Lee, Hwan-Mo

    2016-01-01

    Background N-containing bisphosphonates (BPs), such as pamidronate and risedronate, can inhibit osteoclastic function and reduce osteoclast number by inducing apoptotic cell death in osteoclasts. The aim of this study is to demonstrate the effect of pamidronate, second generation nitrogen-containing BPs and to elucidate matrix metallo-proteinases (MMPs) mRNA expression under serum starvation and/or tumor necrosis factor alpha (TNF-α) stimulation on metabolism of intervertebral disc (IVD) cells in vitro. Methods Firstly, to test the effect of pamidronate on IVD cells in vitro, various concentrations (10-12, 10-10, 10-8, and 10-6 M) of pamidronate were administered to IVD cells. Then DNA and proteoglycan synthesis were measured and messenger RNA (mRNA) expressions of type I collagen, type II collagen, and aggrecan were analyzed. Secondly, to elucidate the expression of MMPs mRNA in human IVD cells under the lower serum status, IVD cells were cultivated in full serum or 1% serum. Thirdly, to elucidate the expression of MMPs mRNA in IVD cells under the stimulation of 1% serum and TNF-α (10 ng/mL) In this study, IVD cells were cultivated in three dimensional alginate bead. Results Under the lower serum culture, IVD cells in alginate beads showed upregulation of MMP 2, 3, 9, 13 mRNA. The cells in lower serum and TNF-α also demonstrated upregulation of MMP-2, 3, 9, and 13 mRNA. The cells with various doses of pamidronate and lower serum and TNF-α were reveled partial down-regulation of MMPs. Conclusions Pamidronate, N-containing second generation BPs, was safe in metabolism of IVD in vitro maintaining chondrogenic phenotype and matrix synthesis, and down-regulated TNF-α induced MMPs expression.

  13. SOD2 deficient erythroid cells up-regulate transferrin receptor and down-regulate mitochondrial biogenesis and metabolism.

    Directory of Open Access Journals (Sweden)

    Florent M Martin

    Full Text Available BACKGROUND: Mice irradiated and reconstituted with hematopoietic cells lacking manganese superoxide dismutase (SOD2 show a persistent hemolytic anemia similar to human sideroblastic anemia (SA, including characteristic intra-mitochondrial iron deposition. SA is primarily an acquired, clonal marrow disorder occurring in individuals over 60 years of age with uncertain etiology. METHODOLOGY/PRINCIPAL FINDINGS: To define early events in the pathogenesis of this murine model of SA, we compared erythroid differentiation of Sod2⁻/⁻ and normal bone marrow cells using flow cytometry and gene expression profiling of erythroblasts. The predominant transcriptional differences observed include widespread down-regulation of mitochondrial metabolic pathways and mitochondrial biogenesis. Multiple nuclear encoded subunits of complexes I-IV of the electron transport chain, ATP synthase (complex V, TCA cycle and mitochondrial ribosomal proteins were coordinately down-regulated in Sod2⁻/⁻ erythroblasts. Despite iron accumulation within mitochondria, we found increased expression of transferrin receptor, Tfrc, at both the transcript and protein level in SOD2 deficient cells, suggesting deregulation of iron delivery. Interestingly, there was decreased expression of ABCb7, the gene responsible for X-linked hereditary SA with ataxia, a component required for iron-sulfur cluster biogenesis. CONCLUSIONS/SIGNIFICANCE: These results indicate that in erythroblasts, mitochondrial oxidative stress reduces expression of multiple nuclear genes encoding components of the respiratory chain, TCA cycle and mitochondrial protein synthesis. An additional target of particular relevance for SA is iron:sulfur cluster biosynthesis. By decreasing transcription of components of cluster synthesis machinery, both iron utilization and regulation of iron uptake are impacted, contributing to the sideroblastic phenotype.

  14. Down-regulation of the oncogene PTTG1 via the KLF6 tumor suppressor during induction of myeloid differentiation.

    Directory of Open Access Journals (Sweden)

    Pei-Yi Chen

    Full Text Available The aberrant expression of proto-oncogenes is involved in processes that are responsible for cellular proliferation and the inhibition of myeloid differentiation in acute myeloid leukemia (AML. Pituitary Tumor-Transforming gene 1 (PTTG1, an oncogenic transcription factor, is abundantly expressed in various human cancers and hematopoietic malignancies. However, its expression in normal leukocytes and most normal tissues is very low or undetectable. The mechanism by which PTTG1 overexpression modifies myeloid cell development and promotes leukemogenesis remain unclear. To investigate the mechanistic links between PTTG1 overexpression and leukemia cell differentiation, we utilized phorbol 12-myristate 13-acetate (PMA, a well-known agent that triggers monocyte/macrophage differentiation, to analyze the expression patterns of PTTG1 in PMA-induced myeloid differentiation. We found that PTTG1 is down-regulated at the transcriptional level in PMA-treated HL-60 and THP1 cells. In addition, we identified a binding site for a tumor suppressor protein, Kruppel-like factor 6 (KLF6, in the PTTG1 promoter. We found that KLF6 could directly bind and repress PTTG1 expression. In HL-60 and THP1 cells, KLF6 mRNA and protein levels are up-regulated with a concordant reduction of PTTG1 expression upon treatment with PMA. Furthermore, KLF6 knockdown by shRNA abolished the suppression of PTTG1 and reduced the activation of the differentiation marker CD11b in PMA-primed cells. The protein kinase C (PKC inhibitor and the MAPK/ERK kinase (MEK inhibitor significantly blocked the potentiation of PMA-mediated KLF6 induction and the down-regulation of PTTG1, indicating that PTTG1 is suppressed via the activation of PKC/ERK/KLF6 pathway. Our findings suggest that drugs that increase the KLF6 inhibition of PTTG1 may have a therapeutic application in AML treatment strategies.

  15. Effect of particle size on the chemisorption and decomposition of carbon monoxide by palladium and nickel clusters

    Science.gov (United States)

    Doering, D. L.; Poppa, H.; Dickinson, J. T.

    1981-01-01

    The chemisorption of gases on well-defined, supported metal particles is a model for basic processes in heterogeneous catalysis. In this study, the chemisorption and decomposition of carbon monoxide on palladium and nickel particles was examined as a function of particle size. Particulate films with average particle sizes ranging from 1 to 10 nm were grown by vapor deposition on UHV-cleaved mica. Successive CO adsorption-desorption cycles resulted in the accumulation of carbon on the particles, which suppressed CO adsorption. The rate of carbon accumulation was strongly dependent on particle size and was higher for Ni than for Pd over the same size range. Carbon was removed from both metals by oxygen treatments at elevated temperatures. However, a mixture of CO and O2 was effective for monitoring the removal of carbon from palladium.

  16. Particle size distribution and property of bacteria attached to carbon fines in drinking water treatment

    Institute of Scientific and Technical Information of China (English)

    Wang Leilei; Chen Wei; Lin Tao

    2008-01-01

    The quantitative change and size distribution of particles in the effluents from a sand filter and a granular activated carbon (GAC) filter in a drinking water treatment plant were investigated. The average total concentration of particles in the sand filter effluent during a filter cycle was 148 particles/mL, 27 of which were larger than 2 μm in size. The concentration in the GAC effluent (561 particles/mL) was significantly greater than that in the sand filter effluent. The concentration of particles larger than 2 μm in the GAC filter effluent reached 201 particles/mL, with the amount of particles with sizes between 2 μm and 15 μm increasing. The most probable number (MPN) of carbon fines reached 43 unit/L after six hours and fines between 0.45 μm and 8.0 μm accounted for more than 50%. The total concentration of outflowing bacteria in the GAC filter effluent, 350 CFU (colony-forming units) /mL, was greater than that in the sand filter effluent, 210 CFU/mL. The desorbed bacteria concentration reached an average of 310 CFU/mg fines. The disinfection efficiency of desorbed bacteria was lower than 40% with 1.5 mg/L of chlorine. The disinfection effect showed that the inactivation rate with 2.0 mg/L of chloramine (90%) was higher than that with chlorine (70%). Experimental results indicated that the high particle concentration in raw water and sedimentation effluent led to high levels of outflowing particles in the sand filter effluent. The activated carbon fines in the effluent accounted for a small proportion of the total particle amount, but the existing bacteria attached to carbon fines may influence the drinking water safety. The disinfection efficiency of desorbed bacteria was lower than that of free bacteria with chlorine, and the disinfection effect on bacteria attached to carbon fines with chloramine was better than that with only chlorine.

  17. On-bicycle exposure to particulate air pollution: Particle number, black carbon, PM2.5, and particle size

    Science.gov (United States)

    Hankey, Steve; Marshall, Julian D.

    2015-12-01

    Inhalation of air pollution during transport is an important exposure pathway, especially for certain modes of travel and types of particles. We measured concentrations of particulate air pollution (particle number [PN], black carbon [BC], fine particles [PM2.5], particle size) using a mobile, bicycle-based monitoring platform during morning and afternoon rush-hour to explore patterns of exposure while cycling (34 days between August 14 and October 16, 2012 in Minneapolis, MN). Measurements were geo-located at 1 ​s intervals along 3 prescribed monitoring routes totaling 85 h (1426 km) of monitoring. Mean morning [afternoon] on-road concentrations were 32,500 [16,600] pt cm-3, 2.5 [0.7] μg m-3 BC, 8.7 [8.3] μg m-3 PM2.5, and 42 [39] nm particle diameter. Concentrations were correlated with street functional class and declined within small distances from a major road (e.g., for PN and BC, mean concentration decreased ∼20% by moving 1 block away from major roads to adjacent local roads). We estimate the share of on-bicycle exposure attributable to near-traffic emissions (vs. regional pollution) is ∼50% for PN and BC; ∼25% for PM2.5. Regression models of instantaneous traffic volumes, derived from on-bicycle video recordings of nearby traffic, quantify the increase in particle-concentrations associated with each passing vehicle; for example, trucks were associated with acute, high concentration exposure events (average concentration-increase per truck: 31,000 pt cm-3, 1.0 μg m-3 PM2.5, 1.6 μg m-3 BC). Our findings could be used to inform design of low-exposure bicycle networks in urban areas.

  18. Disruption of mechanical stress in extracellular matrix is related to Stanford type A aortic dissection through down-regulation of Yes-associated protein

    Science.gov (United States)

    Jiang, Wen-Jian; Ren, Wei-Hong; Liu, Xu-Jie; Liu, Yan; Wu, Fu-Jian; Sun, Li-Zhong; Lan, Feng; Du, Jie; Zhang, Hong-Jia

    2016-01-01

    In this study, we assessed whether the down-regulation of Yes-associated protein (YAP) is involved in the pathogenesis of extracellular matrix (ECM) mechanical stress-induced Stanford type A aortic dissection (STAAD). Human aortic samples were obtained from heart transplantation donors as normal controls and from STAAD patients undergoing surgical replacement of the ascending aorta. Decreased maximum aortic wall velocity, ECM disorders, increased VSMC apoptosis, and YAP down-regulation were identified in STAAD samples. In a mouse model of STAAD, YAP was down-regulated over time during the development of ECM damage, and increased VSMC apoptosis was also observed. YAP knockdown induced VSMC apoptosis under static conditions in vitro, and the change in mechanical stress induced YAP down-regulation and VSMC apoptosis. This study provides evidence that YAP down-regulation caused by the disruption of mechanical stress is associated with the development of STAAD via the induction of apoptosis in aortic VSMCs. As STAAD is among the most elusive and life-threatening vascular diseases, better understanding of the molecular pathogenesis of STAAD is critical to improve clinical outcome. PMID:27608489

  19. Enhancement of Carbon Nanotube Particle Distribution in PPS/PEEK/Carbon Nanotube Ternary Composites with Sausage-Like Structure

    OpenAIRE

    Lin Cao; Shuling Deng; Zhidan Lin

    2016-01-01

    Carbon nanomaterial particles were selectively distributed in an incompatible and high-melting-temperature polymer blend interface, or in a particular phase, to obtain conductive composites. The composite products revealed poor morphology stability and mechanical performance due to processing several times. Poly(phenylene sulfide) (PPS) and poly(ether ether ketone) (PEEK) polymers with large differences of processing temperatures were selected as blend components to obtain a compatible blend....

  20. Optical characterization of nano-sized organic carbon particles emitted from a small gasoline engine

    Institute of Scientific and Technical Information of China (English)

    Bireswar Paul; Amitava Datta; Aparna Datta; Abhijit Saha

    2013-01-01

    The nano-sized organic carbon (NOC) particles emitted from a small gasoline engine were characterized using various ex situ optical techniques to assess their hazardous impact.The exhaust gas was sampled iso-kinetically by a quartz probe and passed through de-ionized water to gather the hydrophilic carbonaceous particulates as hydrosol.The hydrodynamic diameter of the particles ranged between 1.7 and 3.6 nm at no load,with a mean diameter of 2.4 nm.The particle size in the engine exhaust was found to increase at higher loads,which is attributed to coagulation of the particles.The chemical structure of the particles was analyzed using UV-vis and infra-red spectroscopy.Both the band gap energy and oscillator strength data evaluated from the UV-vis absorbance showed that the NOC particles contained polyaromatic hydrocarbon structures with three to five aromatic rings.Infra-red spectroscopy analysis further confirmed the presence of aliphatic and carbonyl functionalities in the aromatic structures of the particles.The fine size of the particles,their high number concentration for the type of the engine under study and their structural features,make the particles extremely hazardous for environment and health.

  1. Carbon Mineralization in Two Ultisols Amended with Different Sources and Particle Sizes of Pyrolyzed Biochar

    Science.gov (United States)

    Biochar produced during pyrolysis has the potential to enhance soil fertility and reduce greenhouse gas emissions. The influence of biochar properties (e.g., particle size) on both short- and long-term carbon (C) mineralization of biochar remains unclear. There is minimal informa...

  2. Adsorption of NO{sub 2} on carbon aerosols particles at the low ppb-level

    Energy Technology Data Exchange (ETDEWEB)

    Kalberer, M.; Ammann, M.; Baltensperger, U.; Gaeggeler, H.W. [Paul Scherrer Inst. (PSI), Villigen (Switzerland)

    1997-09-01

    The adsorption of NO{sub 2} at the low ppb-level (3-40 ppb) on carbon aerosol particles was investigated. A sticking coefficient of about 2.10{sup -4} was found, similar to that in previous studies using radioactively labeled {sup 13}NO{sub 2}. (author) 2 figs., 2 refs.

  3. Carbon mediated reduction of silicon dioxide and growth of copper silicide particles in uniform width channels

    DEFF Research Database (Denmark)

    Pizzocchero, Filippo; Bøggild, Peter; Booth, Tim

    2013-01-01

    We show that surface arc-discharge deposited carbon plays a critical intermediary role in the breakdown of thermally grown oxide diffusion barriers of 90 nm on a silicon wafer at 1035°C in an Ar/H2 atmosphere, resulting in the formation of epitaxial copper silicide particles in ≈ 10 μm wide...

  4. PULMONARY AND CARDIAC GENE EXPRESSION FOLLOWING ACUTE ULTRAFINE CARBON PARTICLE INHALATION IN HYPERTENSIVE RATS

    Science.gov (United States)

    Inhalation of ultrafine carbon particles (ufCP) causes cardiac physiological changes without marked pulmonary injury or inflammation. We hypothesized that acute ufCP exposure of 13 months old Spontaneously Hypertensive (SH) rats will cause differential effects on the lung and hea...

  5. Carbon and particle removal from EUV reticles by shielded microwave induced remote plasma

    NARCIS (Netherlands)

    Koster, N.B.; Molkenboer, F.; Veldhoven, E. van; Maas, D.J.; Verberk, R.

    2010-01-01

    For EUVL to be successful it is essential that reticles can be made without defects and that they can be cleaned without causing any damage. Contamination of reticles can be in two ways: particles due to handling can cause printable defects and carbon contamination due to residual hydrocarbons can c

  6. CARDIOVASCULAR RESPONSES IN UNRESTRAINED WKY-RATS TO INHALED ULTRAFINE CARBON PARTICLES

    Science.gov (United States)

    AbstractThis study provides evidence for adverse cardiac effects of inhaled ultrafine particles (UFPs) in healthy WKY rats. Short term exposure (24 h) with carbon UFPs (180 ?g?m ?) induced a moderate but significant heart rate increase of 18 bpm (4.8 %) in association with a ...

  7. Editor's Highlight: Neonatal Activation of the Xenobiotic-Sensors PXR and CAR Results in Acute and Persistent Down-regulation of PPARα-Signaling in Mouse Liver.

    Science.gov (United States)

    Li, Cindy Yanfei; Cheng, Sunny Lihua; Bammler, Theo K; Cui, Julia Yue

    2016-10-01

    Safety concerns have emerged regarding the potential long-lasting effects due to developmental exposure to xenobiotics. The pregnane X receptor (PXR) and constitutive androstane receptor (CAR) are critical xenobiotic-sensing nuclear receptors that are highly expressed in liver. The goal of this study was to test our hypothesis that neonatal exposure to PXR- or CAR-activators not only acutely but also persistently regulates the expression of drug-processing genes (DPGs). A single dose of the PXR-ligand PCN (75 mg/kg), CAR-ligand TCPOBOP (3 mg/kg), or vehicle (corn oil) was administered intraperitoneally to 3-day-old neonatal wild-type mice. Livers were collected 24 h post-dose or from adult mice at 60 days of age, and global gene expression of these mice was determined using Affymetrix Mouse Transcriptome Assay 1.0. In neonatal liver, PCN up-regulated 464 and down-regulated 449 genes, whereas TCPOBOP up-regulated 308 and down-regulated 112 genes. In adult liver, there were 15 persistently up-regulated and 22 persistently down-regulated genes following neonatal exposure to PCN, as well as 130 persistently up-regulated and 18 persistently down-regulated genes following neonatal exposure to TCPOBOP. Neonatal exposure to both PCN and TCPOBOP persistently down-regulated multiple Cyp4a members, which are prototypical-target genes of the lipid-sensor PPARα, and this correlated with decreased PPARα-binding to the Cyp4a gene loci. RT-qPCR, western blotting, and enzyme activity assays in livers of wild-type, PXR-null, and CAR-null mice confirmed that the persistent down-regulation of Cyp4a was PXR and CAR dependent. In conclusion, neonatal exposure to PXR- and CAR-activators both acutely and persistently regulates critical genes involved in xenobiotic and lipid metabolism in liver.

  8. Stress conditions promote yeast Gap1 permease ubiquitylation and down-regulation via the arrestin-like Bul and Aly proteins.

    Science.gov (United States)

    Crapeau, Myriam; Merhi, Ahmad; André, Bruno

    2014-08-01

    Gap1, the yeast general amino acid permease, is a convenient model for studying how the intracellular traffic of membrane transporters is regulated. Present at the plasma membrane under poor nitrogen supply conditions, it undergoes ubiquitylation, endocytosis, and degradation upon activation of the TORC1 kinase complex in response to an increase in internal amino acids. This down-regulation is stimulated by TORC1-dependent phosphoinhibition of the Npr1 kinase, resulting in activation by dephosphorylation of the arrestin-like Bul1 and Bul2 adaptors recruiting the Rsp5 ubiquitin ligase to Gap1. We report here that Gap1 is also down-regulated when cells are treated with the TORC1 inhibitor rapamycin or subjected to various stresses and that a lack of the Tco89 subunit of TORC1 causes constitutive Gap1 down-regulation. Both the Bul1 and Bul2 and the Aly1 and Aly2 arrestin-like adaptors of Rsp5 promote this down-regulation without undergoing dephosphorylation. Furthermore, they act via the C-terminal regions of Gap1 not involved in ubiquitylation in response to internal amino acids, whereas a Gap1 mutant altered in the N-terminal tail and resistant to ubiquitylation by internal amino acids is efficiently down-regulated under stress via the Bul and Aly adaptors. Although the Bul proteins mediate Gap1 ubiquitylation of two possible lysines, Lys-9 and Lys-16, the Aly proteins promote ubiquitylation of the Lys-16 residue only. This stress-induced pathway of Gap1 down-regulation targets other permeases as well, and it likely allows cells facing adverse conditions to retrieve amino acids from permease degradation.

  9. Influence of the particle size of activated mineral carbon on the phenol and chlorophenol adsorption

    International Nuclear Information System (INIS)

    Water pollution by phenolic compounds is a problem that requires a solution since these phenolic compounds are not completely biodegradable, they accumulate through the food chains and they are quite toxic when enter in contact with living organisms. In human beings, ingestion or contact of the skin with this type of compounds produces irritation and damages mainly to the liver and kidneys. In fact, the Environmental Protection Agency of the United States (EPA assigned nine phenolic compounds among the 275 most toxic substances in 1991. Phenols are found in wastewater from agriculture and industry, because phenolic compounds are used as pesticides and in diverse industrial activities. The treatment of this type of water is not simple because they are generally composed of a mixture of residuals with different chemical nature A useful method for the removal of phenols is the adsorption by activated carbon, since this material has a great surface area and it can be regenerated. The adsorption process depends, among other factors, on the activated carbon characteristics. When they are modified, their capacity to remove pollutants from the water changes. The effect of activated carbon particle size on the removal of phenolic compounds has not been completely studied. Therefore, the aim of this work was to determine the influence of the mineral activated carbon particle size on the phenol and 4-chloro phenol adsorption in aqueous solution, on adsorption column system. The results of the present work indicate that the mineral activated carbon particle size has a very important influence on the adsorption of phenol and 4-chloro phenol. When the particles were smaller, the retention quantities of phenol and 4-chloro phenol increased. This behavior was related to the particle characteristics of the mineral activated carbon such as surface area and pore volume, while other factors such as elementary composition of the activated carbon did not influence the adsorption process

  10. Sources and mixing state of size-resolved elemental carbon particles in a European megacity: Paris

    Directory of Open Access Journals (Sweden)

    R. M. Healy

    2012-02-01

    Full Text Available An Aerosol Time-Of-Flight Mass Spectrometer (ATOFMS was deployed to investigate the size-resolved chemical composition of single particles at an urban background site in Paris, France, as part of the MEGAPOLI winter campaign in January/February 2010. ATOFMS particle counts were scaled to match coincident Twin Differential Mobility Particle Sizer (TDMPS data in order to generate hourly size-resolved mass concentrations for the single particle classes observed. The total scaled ATOFMS particle mass concentration in the size range 150–1067 nm was found to agree very well with the sum of concurrent High-Resolution Time-of-Flight Aerosol Mass Spectrometer (HR-ToF-AMS and Multi-Angle Absorption Photometer (MAAP mass concentration measurements of organic carbon (OC, inorganic ions and black carbon (BC (R2 = 0.91. Clustering analysis of the ATOFMS single particle mass spectra allowed the separation of elemental carbon (EC particles into four classes: (i EC attributed to biomass burning (ECbiomass, (ii EC attributed to traffic (ECtraffic, (iii EC internally mixed with OC and ammonium sulfate (ECOCSOx, and (iv EC internally mixed with OC and ammonium nitrate (ECOCNOx. Average hourly mass concentrations for EC-containing particles detected by the ATOFMS were found to agree reasonably well with semi-continuous quantitative thermal/optical EC and optical BC measurements (r2 = 0.61 and 0.65–0.68 respectively, n = 552. The EC particle mass assigned to fossil fuel and biomass burning sources also agreed reasonably well with BC mass fractions assigned to the same sources using seven-wavelength aethalometer data (r2 = 0.60 and 0.48, respectively, n = 568. Agreement between the ATOFMS and other instrumentation improved noticeably when a period influenced by significantly aged, internally mixed EC particles was removed from the intercomparison. 88% and 12% of EC particle

  11. Sources and mixing state of size-resolved elemental carbon particles in a European megacity: Paris

    Science.gov (United States)

    Healy, R. M.; Sciare, J.; Poulain, L.; Kamili, K.; Merkel, M.; Müller, T.; Wiedensohler, A.; Eckhardt, S.; Stohl, A.; Sarda-Estève, R.; McGillicuddy, E.; O'Connor, I. P.; Sodeau, J. R.; Wenger, J. C.

    2012-02-01

    An Aerosol Time-Of-Flight Mass Spectrometer (ATOFMS) was deployed to investigate the size-resolved chemical composition of single particles at an urban background site in Paris, France, as part of the MEGAPOLI winter campaign in January/February 2010. ATOFMS particle counts were scaled to match coincident Twin Differential Mobility Particle Sizer (TDMPS) data in order to generate hourly size-resolved mass concentrations for the single particle classes observed. The total scaled ATOFMS particle mass concentration in the size range 150-1067 nm was found to agree very well with the sum of concurrent High-Resolution Time-of-Flight Aerosol Mass Spectrometer (HR-ToF-AMS) and Multi-Angle Absorption Photometer (MAAP) mass concentration measurements of organic carbon (OC), inorganic ions and black carbon (BC) (R2 = 0.91). Clustering analysis of the ATOFMS single particle mass spectra allowed the separation of elemental carbon (EC) particles into four classes: (i) EC attributed to biomass burning (ECbiomass), (ii) EC attributed to traffic (ECtraffic), (iii) EC internally mixed with OC and ammonium sulfate (ECOCSOx), and (iv) EC internally mixed with OC and ammonium nitrate (ECOCNOx). Average hourly mass concentrations for EC-containing particles detected by the ATOFMS were found to agree reasonably well with semi-continuous quantitative thermal/optical EC and optical BC measurements (r2 = 0.61 and 0.65-0.68 respectively, n = 552). The EC particle mass assigned to fossil fuel and biomass burning sources also agreed reasonably well with BC mass fractions assigned to the same sources using seven-wavelength aethalometer data (r2 = 0.60 and 0.48, respectively, n = 568). Agreement between the ATOFMS and other instrumentation improved noticeably when a period influenced by significantly aged, internally mixed EC particles was removed from the intercomparison. 88% and 12% of EC particle mass was apportioned to fossil fuel and biomass burning respectively using the ATOFMS data

  12. Sources and mixing state of size-resolved elemental carbon particles in a European megacity: Paris

    Directory of Open Access Journals (Sweden)

    R. M. Healy

    2011-11-01

    Full Text Available An Aerosol Time-Of-Flight Mass Spectrometer (ATOFMS was deployed to investigate the size-resolved chemical composition of single particles at an urban background site in Paris, France, as part of the MEGAPOLI winter campaign in January/February 2010. ATOFMS particle counts were scaled to match coincident Twin Differential Mobility Particle Sizer (TDMPS data in order to generate hourly size-resolved mass concentrations for the single particle classes observed. The total scaled ATOFMS particle mass concentration in the size range 150–1067 nm was found to agree very well with the sum of concurrent High-Resolution Time-of-Flight Aerosol Mass Spectrometer (HR-ToF-AMS and Multi-Angle Absorption Photometer (MAAP mass concentration measurements of organic carbon (OC, inorganic ions and black carbon (BC (R2 = 0.91. Clustering analysis of the ATOFMS single particle mass spectra allowed the separation of elemental carbon (EC particles into four classes: (i EC attributed to biomass burning (ECbiomass, (ii EC attributed to traffic (ECtraffic, (iii EC internally mixed with OC and ammonium sulfate (ECOCSOx, and (iv EC internally mixed with OC and ammonium nitrate (ECOCNOx. Average hourly mass concentrations for EC-containing particles detected by the ATOFMS were found to agree reasonably well with semi-continuous quantitative thermal/optical EC and optical BC measurements (r2 = 0.61 and 0.65–0.68, respectively, n = 552. The EC particle mass assigned to fossil fuel and biomass burning sources also agreed reasonably well with BC mass fractions assigned to the same sources using seven-wavelength aethalometer data (r2 = 0.60 and 0.48, respectively, n = 568. Agreement between the ATOFMS and other instrumentation improved noticeably when a period influenced by significantly aged, internally mixed EC particles was removed from the intercomparison. 88 % and 12 % of EC

  13. Down-Regulation of the kps Region 1 Capsular Assembly Operon following Attachment of Escherichia coli Type 1 Fimbriae to d-Mannose Receptors

    OpenAIRE

    Schwan, William R.; Beck, Michael T.; Hultgren, Scott J.; Pinkner, Jerry; Woolever, Nathan L.; Larson, Thomas

    2005-01-01

    A differential-display PCR procedure identified the capsular assembly gene kpsD after Escherichia coli type 1 fimbrial binding to mannose-coated Sepharose beads. Limiting-dilution reverse-transcribed PCRs confirmed down-regulation of the kpsD gene, and Northern blot and lacZ fusion analyses showed down-regulation of the kpsFEDUCS region 1 operon. KpsD protein levels fell, and an agglutination test showed less K capsular antigen on the surface following the bacterial ligand-receptor interactio...

  14. Down-regulation of PPARgamma1 suppresses cell growth and induces apoptosis in MCF-7 breast cancer cells

    Directory of Open Access Journals (Sweden)

    Wallis Natalie K

    2008-12-01

    Full Text Available Abstract Background Peroxisome proliferator-activated receptor gamma (PPARγ is a member of the nuclear hormone receptor superfamily and is highly expressed in many human tumors including breast cancer. PPARγ has been identified as a potential target for breast cancer therapy based on the fact that its activation by synthetic ligands affects the differentiation, proliferation, and apoptosis of cancer cells. However, the controversial nature of current studies and disappointing results from clinical trials raise questions about the contribution of PPARγ signaling in breast cancer development in the absence of stimulation by exogenous ligands. Recent reports from both in vitro and in vivo studies are inconsistent and suggest that endogenous activation of PPARγ plays a much more complex role in initiation and progression of cancer than previously thought. Results We have previously demonstrated that an increase in expression of PPARγ1 in MCF-7 breast cancer cells is driven by a tumor-specific promoter. Myc-associated zinc finger protein (MAZ was identified as a transcriptional mediator of PPARγ1 expression in these cells. In this study, using RNA interference (RNAi to inhibit PPARγ1 expression directly or via down-regulation of MAZ, we report for the first time that a decrease in PPARγ1 expression results in reduced cellular proliferation in MCF-7 breast cancer cells. Furthermore, we demonstrate that these changes in proliferation are associated with a significant decrease in cell transition from G1 to the S phase. Using a dominant-negative mutant of PPARγ1, Δ462, we confirmed that PPARγ1 acts as a pro-survival factor and showed that this phenomenon is not limited to MCF-7 cells. Finally, we demonstrate that down-regulation of PPARγ1 expression leads to an induction of apoptosis in MCF-7 cells, confirmed by analyzing Bcl-2 expression and PARP-1 cleavage. Conclusion Thus, these findings suggest that an increase in PPARγ1 signaling

  15. Modified super-long down-regulation protocol improves fertilization and pregnancy in patients with poor ovarian responses

    Institute of Scientific and Technical Information of China (English)

    ZHANG Hui-juan; SONG Xue-ru; L(U) Rui; XUE Feng-xia

    2012-01-01

    Background The successful end-point of in vitro fertilization (IVF) treatment is for a woman to give live birth.This outcome is based on various factors including adequate number of retrieved eggs.Failure to recruit adequate follicles,from which the eggs are retrieved,is called a "poor response".How to improve the clinical pregnancy rates of poor responders was one of the tough problems for IVF.Methods The study involved 51 patients who responded poorly to high dose gonadotropin treatment in their previous cycles at our reproductive center,between April 2010 and February 2012.The previous cycle (group A) received routine long protocol; the subsequent cycle (group B) received modified super-long down-regulation protocol.The primary outcome of the study was the number of oocytes fertilized.The increase in the pregnancy rate was the secondary outcome.Differences between the groups were assessed by using Student's t test and x2 test where appropriate.Results The patients' average age was (36.64±3.85) years.The mean duration of ovarian stimulation cycles of the group A patients was longer than those of the group B patients.The total dose of follicle-stimulating hormone (FSH) was significantly lower in the subsequent cycle.The peak value of serum estradiol on human chorionic gonadotrophin (hCG) day was lower in group A as compared with group B.The number of metaphase Ⅱ oocytes recovered was significantly higher in group B.The cleavage rate in group A was significantly lower than in group B,49 patients in group B reached embryo transfer stage,while 46 patients in group A reached this stage.Patients in group B received significantly more embryos per transfer as compared with group A.More pregnancies and more clinical pregnancies with fetal heart activity were achieved in group B.Conclusions This comparative trial shows that poor responder women undergoing repeated assisted reproduction treatment using modified super-long down-regulation protocol achieve more oocytes

  16. Particle size effects in Fischer-Tropsch synthesis by Co catalyst supported on carbon nanotubes

    Institute of Scientific and Technical Information of China (English)

    Ali Nakhaei Pour; Elham Hosaini; Mohammad Izadyar; Mohammad Reza Housaindokht

    2015-01-01

    The effect of Co particle size on the Fischer-Tropsch synthesis (FTS) activity of carbon nanotube (CNT)-supported Co catalysts was investigated. Microemulsion (using water-to-surfactant molar ratios of 2 to12) and impregnation techniques were used to prepare catalysts with different Co particle sizes. Kinetic studies were performed to understand the effect of Co particle size on catalytic activity. Size-dependent kinetic parameters were developed using a thermodynamic method, to evaluate the structural sensitivity of the CNT-supported Co catalysts. The size-independent FTS reaction rate constant and size-independent adsorption parameter increased with increasing reac-tion temperature. The Polani parameter also depended on catalyst particle size, because of changes in the catalyst surface coverage.

  17. Particle size and crystallographic orientation controlled electrodeposition of platinum nanoparticles on carbon nanotubes

    International Nuclear Information System (INIS)

    Highlights: • Particle size controlled electrodeposition of platinum on carbon nanotubes. • Control on crystallographic orientation of platinum surface is demonstrated. • Catalytic activity shows considerable dependence on crystallographic orientation. - Abstract: Platinum-coated carbon nanotubes (Pt/CNTs) with desired particle size and preferred surface crystallographic orientations have a variety of applications in diverse fields. Pt/CNTs having uniform dispersion of Pt nanoparticles are synthesized via electrodeposition route using CNT coated carbon fiber as the working electrode and H2PtCl6.6H2O as Pt precursor. Particle size and crystallographic orientation of Pt nanoparticles are controlled by using polyvinylpyrrolidone (PVP) as the protecting agent during electrodeposition in H2SO4 or HCl containing coating baths. Cyclic voltammetric study and X-ray diffraction analysis suggest Pt(100) surface enrichment of Pt nanoparticles in presence of PVP, which increases with increasing PVP concentration. Although the Pt deposition rate decreases significantly in presence of Cl− ions, the enrichment effect is observed both in the H2SO4 as well as the HCl containing baths. The Pt/CNT synthesized in presence of PVP exhibit higher oxygen reduction reaction activity (acidic media) and methanol oxidation activity compared to that synthesized without PVP. The process may be utilized to synthesize Pt based electrocatalysts with controlled particle size and preferred surface orientation

  18. The ir emission features: Emission from PAH [Polycyclic Aromatic Hydrocarbons] molecules and amorphous carbon particles

    International Nuclear Information System (INIS)

    PAHs can have several forms in the interstellar medium. To assess the importance of each requires the availability of a collection of high quality, complete mid-ir interstellar emission spectra, a collection of laboratory spectra of PAH samples prepared under realistic conditions and a firm understanding of the microscopic emission mechanism. Given what we currently know about PAHs, the spectroscopic data suggests that there are at least two components which contribute to the interstellar emission spectrum: free molecule sized PAHs producing the narrow features and amorphous carbon particles (which are primarily made up of an irregular ''lattice'' of PAHs) contributing to the broad underlying components. An exact treatment of the ir fluorescence from highly vibrationally excited large molecules shows that species containing between 20 and 30 carbon atoms are responsible for the narrow features, although the spectra match more closely with the spectra of amorphous carbon particles. Since little is known about the spectroscopic properties of free PAHs and PAH clusters, much laboratory work is called for in conjunction with an observational program which focuses on the spatial characteristics of the spectra. In this way the distribution and evolution of carbon from molecule to particle can be traced. 38 refs., 9 figs

  19. Decomposition and particle release of a carbon nanotube/epoxy nanocomposite at elevated temperatures

    Energy Technology Data Exchange (ETDEWEB)

    Schlagenhauf, Lukas [Empa - Swiss Federal Laboratories for Materials Science and Technology, Laboratory for Functional Polymers (Switzerland); Kuo, Yu-Ying; Bahk, Yeon Kyoung [Empa - Swiss Federal Laboratories for Materials Science and Technology, Laboratory for Advanced Analytical Technologies (Switzerland); Nüesch, Frank [Empa - Swiss Federal Laboratories for Materials Science and Technology, Laboratory for Functional Polymers (Switzerland); Wang, Jing, E-mail: Jing.Wang@ifu.baug.ethz.ch [Empa - Swiss Federal Laboratories for Materials Science and Technology, Laboratory for Advanced Analytical Technologies (Switzerland)

    2015-11-15

    Carbon nanotubes (CNTs) as fillers in nanocomposites have attracted significant attention, and one of the applications is to use the CNTs as flame retardants. For such nanocomposites, possible release of CNTs at elevated temperatures after decomposition of the polymer matrix poses potential health threats. We investigated the airborne particle release from a decomposing multi-walled carbon nanotube (MWCNT)/epoxy nanocomposite in order to measure a possible release of MWCNTs. An experimental set-up was established that allows decomposing the samples in a furnace by exposure to increasing temperatures at a constant heating rate and under ambient air or nitrogen atmosphere. The particle analysis was performed by aerosol measurement devices and by transmission electron microscopy (TEM) of collected particles. Further, by the application of a thermal denuder, it was also possible to measure non-volatile particles only. Characterization of the tested samples and the decomposition kinetics were determined by the usage of thermogravimetric analysis (TGA). The particle release of different samples was investigated, of a neat epoxy, nanocomposites with 0.1 and 1 wt% MWCNTs, and nanocomposites with functionalized MWCNTs. The results showed that the added MWCNTs had little effect on the decomposition kinetics of the investigated samples, but the weight of the remaining residues after decomposition was influenced significantly. The measurements with decomposition in different atmospheres showed a release of a higher number of particles at temperatures below 300 °C when air was used. Analysis of collected particles by TEM revealed that no detectable amount of MWCNTs was released, but micrometer-sized fibrous particles were collected.

  20. E3B1/ABI-1 Isoforms Are Down-Regulated in Cancers of Human Gastrointestinal Tract

    Directory of Open Access Journals (Sweden)

    Rafia A. Baba

    2012-01-01

    Full Text Available The expression of E3B1/ABI-1 protein and its role in cancer progression and prognosis are largely unknown in the majority of solid tumors. In this study, we examined the expression pattern of E3B1/ABI-1 protein in histologically confirmed cases of esophageal (squamous cell carcinoma and adenocarcinoma, gastro-esophageal junction, colorectal cancers and corresponding normal tissues freshly resected from a cohort of 135 patients, by Western Blotting and Immunofluorescence Staining. The protein is present in its phosphorylated form in cells and tissues. Depending on the extent of phosphorylation it is either present in hyper-phosphorylated (M. Wt. 72 kDa form or in hypo-phosphorylated form (M. Wt. 68 kDa and 65 kDa. A thorough analysis revealed that expression of E3B1/ABI-1 protein is significantly decreased in esophageal, gastro-esophageal junction and colorectal carcinomas irrespective of age, gender, dietary and smoking habits of the patients. The decrease in expression of E3B1/ABI-1 was consistently observed for all the three isoforms. However, the decrease in the expression of isoforms varied with different forms of cancers. Down-regulation of E3B1/ABI-1 expression in human carcinomas may play a critical role in tumor progression and in determining disease prognosis.

  1. Induction of autophagy by Imatinib sequesters Bcr-Abl in autophagosomes and down-regulates Bcr-Abl protein.

    LENUS (Irish Health Repository)

    Elzinga, Baukje M

    2013-06-01

    Chronic Myeloid Leukemia (CML) is a disease of hematopoietic stem cells which harbor the chimeric gene Bcr-Abl. Expression levels of this constitutively active tyrosine kinase are critical for response to tyrosine kinase inhibitor treatment and also disease progression, yet the regulation of protein stability is poorly understood. We have previously demonstrated that imatinib can induce autophagy in Bcr-Abl expressing cells. Autophagy has been associated with the clearance of large macromolecular signaling complexes and abnormal proteins, however, the contribution of autophagy to the turnover of Bcr-Abl protein in imatinib treated cells is unknown. In this study, we show that following imatinib treatment, Bcr-Abl is sequestered into vesicular structures that co-localize with the autophagy marker LC3 or GABARAP. This association is inhibited by siRNA mediated knockdown of autophagy regulators (Beclin 1\\/ATG7). Pharmacological inhibition of autophagy also reduced Bcr-Abl\\/LC3 co-localization in both K562 and CML patient cells. Bcr-Abl protein expression was reduced with imatinib treatment. Inhibition of both autophagy and proteasome activity in imatinib treated cells was required to restore Bcr-Abl protein levels to those of untreated cells. This ability to down-regulate Bcr-Abl protein levels through the induction of autophagy may be an additional and important feature of the activity of imatinib.

  2. Asiaticoside attenuates lipopolysaccharide-induced acute lung injury via down-regulation of NF-κB signaling pathway.

    Science.gov (United States)

    Qiu, Jiaming; Yu, Lijun; Zhang, Xingxing; Wu, Qianchao; Wang, Di; Wang, Xiuzhi; Xia, Cheng; Feng, Haihua

    2015-05-01

    Asiaticoside (AS), a triterpene glycoside isolated from Centella asiatica, has been shown to possess potent anti-inflammatory activity. However, the detailed molecular mechanisms of AS on lipopolysaccharide (LPS)-induced acute lung injury (ALI) model in mice are scanty. The purpose of this study was to evaluate the effect of AS on LPS-induced mouse ALI via down-regulation of NF-κB signaling pathway. We investigated the efficacy of AS on cytokine levels induced by LPS in bronchoalveolar lavage fluid (BALF) and RAW 264.7 cells. The production of cytokine (TNF-α and IL-6) was measured by enzyme-linked immunosorbent assay (ELISA). The lung wet-to-dry weight ratios were measured in LPS-challenged mice, and lung histopathologic changes observed via paraffin section were assessed. To further study the mechanism of AS protective effects on ALI, the activation of NF-κB p65 subunit and the degradation of IκBα were tested by western blot assay. We found that AS treatment at 15, 30 or 45mg/kg dose-dependently attenuated LPS-induced pulmonary inflammation by reducing inflammatory infiltration, histopathological changes, descended cytokine production, and pulmonary edema initiated by LPS. Furthermore, our results suggested that AS suppressed inflammatory responses in LPS-induced ALI through inhibition of the phosphorylation of NF-κB p65 subunit and the degradation of its inhibitor IκBα, and might be a new preventive agent of ALI in the clinical setting.

  3. The reported clinical utility of taurine in ischemic disorders may reflect a down-regulation of neutrophil activation and adhesion.

    Science.gov (United States)

    McCarty, M F

    1999-10-01

    The first publications regarding clinical use of taurine were Italian reports claiming therapeutic efficacy in angina, intermittent claudication and symptomatic cerebral arteriosclerosis. A down-regulation of neutrophil activation and endothelial adhesion might plausibly account for these observations. Endothelial platelet-activating factor (PAF) is a crucial stimulus to neutrophil adhesion and activation, whereas endothelial nitric oxide (NO) suppresses PAF production and acts in various other ways to antagonize binding and activation of neutrophils. Hypochlorous acid (HOCl), a neutrophil product which avidly oxidizes many sulfhydryl-dependent proteins, can be expected to inhibit NO synthase while up-regulating PAF generation; thus, a vicious circle can be postulated whereby HOCl released by marginating neutrophils acts on capillary or venular endothelium to promote further neutrophil adhesion and activation. Taurine is the natural detoxicant of HOCl, and thus has the potential to intervene in this vicious circle, promoting a less adhesive endothelium and restraining excessive neutrophil activation. Agents which inhibit the action of PAF on neutrophils, such as ginkgolides and pentoxifylline, have documented utility in ischemic disorders and presumably would complement the efficacy of taurine in this regard. Fish oil, which inhibits endothelial expression of various adhesion factors and probably PAF as well, and which suppresses neutrophil leukotriene production, may likewise be useful in ischemia. These agents may additionally constitute a non-toxic strategy for treating inflammatory disorders in which activated neutrophils play a prominent pathogenic role. Double-blind studies to confirm the efficacy of taurine in symptomatic chronic ischemia are needed.

  4. Onset of quiescence following p53 mediated down-regulation of H2AX in normal cells.

    Directory of Open Access Journals (Sweden)

    Yuko Atsumi

    Full Text Available Normal cells, both in vivo and in vitro, become quiescent after serial cell proliferation. During this process, cells can develop immortality with genomic instability, although the mechanisms by which this is regulated are unclear. Here, we show that a growth-arrested cellular status is produced by the down-regulation of histone H2AX in normal cells. Normal mouse embryonic fibroblast cells preserve an H2AX diminished quiescent status through p53 regulation and stable-diploidy maintenance. However, such quiescence is abrogated under continuous growth stimulation, inducing DNA replication stress. Because DNA replication stress-associated lesions are cryptogenic and capable of mediating chromosome-bridge formation and cytokinesis failure, this results in tetraploidization. Arf/p53 module-mutation is induced during tetraploidization with the resulting H2AX recovery and immortality acquisition. Thus, although cellular homeostasis is preserved under quiescence with stable diploidy, tetraploidization induced under growth stimulation disrupts the homeostasis and triggers immortality acquisition.

  5. Systemic down-regulation of delta-9 desaturase promotes muscle oxidative metabolism and accelerates muscle function recovery following nerve injury.

    Directory of Open Access Journals (Sweden)

    Ghulam Hussain

    Full Text Available The progressive deterioration of the neuromuscular axis is typically observed in degenerative conditions of the lower motor neurons, such as amyotrophic lateral sclerosis (ALS. Neurodegeneration in this disease is associated with systemic metabolic perturbations, including hypermetabolism and dyslipidemia. Our previous gene profiling studies on ALS muscle revealed down-regulation of delta-9 desaturase, or SCD1, which is the rate-limiting enzyme in the synthesis of monounsaturated fatty acids. Interestingly, knocking out SCD1 gene is known to induce hypermetabolism and stimulate fatty acid beta-oxidation. Here we investigated whether SCD1 deficiency can affect muscle function and its restoration in response to injury. The genetic ablation of SCD1 was not detrimental per se to muscle function. On the contrary, muscles in SCD1 knockout mice shifted toward a more oxidative metabolism, and enhanced the expression of synaptic genes. Repressing SCD1 expression or reducing SCD-dependent enzymatic activity accelerated the recovery of muscle function after inducing sciatic nerve crush. Overall, these findings provide evidence for a new role of SCD1 in modulating the restorative potential of skeletal muscles.

  6. Perception adapts via top-down regulation to task repetition: A Lotka-Volterra-Haken modeling analysis of experimental data.

    Science.gov (United States)

    Frank, T D

    2016-03-01

    Two experiments are reported in which participants perceived different physical quantities: size and speed. The perceptual tasks were performed in the context of motor performance problems. Participants perceived the size of objects in order to grasp the objects single handed or with both hands. Likewise, participants perceived the speed of a moving treadmill in order to control walking or running at that speed. In both experiments, the perceptual tasks were repeatedly performed by the participants while the to-be-perceived quantity was gradually varied from small to large objects (Experiment 1) and from low to high speeds (Experiment 2). Hysteresis with negative sign was found when participants were not allowed to execute the motor component, that is, when the execution stage was decoupled from the planning stage. No such effect was found in the control condition, when participants were allowed to execute the motor action. Using a Lotka-Volterra-Haken model for two competing neural populations, it is argued that the observations are consistent with the notion that the repetitions induce an adaptation effect of the perceptual system via top-down regulation. Moreover, the amount of synaptic modulation involved in the adaptation is estimated from participant data. PMID:26678820

  7. Overexpressed ubiquitin ligase Cullin7 in breast cancer promotes cell proliferation and invasion via down-regulating p53

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Hongsheng [Department of Histology and Embryology, Guangdong Medical College, Dongguan 523808, Guangdong (China); Wu, Fenping [The 7th People’s Hospital of Chengdu, Chengdu 610041, Sichuan (China); Wang, Yan [The Second School of Clinical Medicine, Guangdong Medical College, Dongguan 523808, Guangdong (China); Yan, Chong [School of Pharmacy, Guangdong Medical College, Dongguan 523808, Guangdong (China); Su, Wenmei, E-mail: wenmeisutg@126.com [Oncology of Affiliated Hospital Guangdong Medical College, Zhanjiang 524000, Guangdong (China)

    2014-08-08

    Highlights: • Cullin7 is overexpressed in human breast cancer samples. • Cullin7 stimulated proliferation and invasion of breast cancer cells. • Inhibition of p53 contributes to Cullin7-induced proliferation and invasion. - Abstract: Ubiquitin ligase Cullin7 has been identified as an oncogene in some malignant diseases such as choriocarcinoma and neuroblastoma. However, the role of Cullin7 in breast cancer carcinogenesis remains unclear. In this study, we compared Cullin7 protein levels in breast cancer tissues with normal breast tissues and identified significantly higher expression of Cullin7 protein in breast cancer specimens. By overexpressing Cullin7 in breast cancer cells HCC1937, we found that Cullin7 could promote cell growth and invasion in vitro. In contrast, the cell growth and invasion was inhibited by silencing Cullin7 in breast cancer cell BT474. Moreover, we demonstrated that Cullin7 promoted breast cancer cell proliferation and invasion via down-regulating p53 expression. Thus, our study provided evidence that Cullin7 functions as a novel oncogene in breast cancer and may be a potential therapeutic target for breast cancer management.

  8. eEF-2 Phosphorylation Down-Regulates P-Glycoprotein Over-Expression in Rat Brain Microvessel Endothelial Cells.

    Directory of Open Access Journals (Sweden)

    Xing Hua Tang

    Full Text Available We investigated whether glutamate, NMDA receptors, and eukaryote elongation factor-2 kinase (eEF-2K/eEF-2 regulate P-glycoprotein expression, and the effects of the eEF-2K inhibitor NH125 on the expression of P-glycoprotein in rat brain microvessel endothelial cells (RBMECs.Cortex was obtained from newborn Wistar rat brains. After surface vessels and meninges were removed, the pellet containing microvessels was resuspended and incubated at 37°C in culture medium. Cell viability was assessed by the MTT assay. RBMECs were identified by immunohistochemistry with anti-vWF. P-glycoprotein, phospho-eEF-2, and eEF-2 expression were determined by western blot analysis. Mdr1a gene expression was analyzed by RT-PCR.Mdr1a mRNA, P-glycoprotein and phospho-eEF-2 expression increased in L-glutamate stimulated RBMECs. P-glycoprotein and phospho-eEF-2 expression were down-regulated after NH125 treatment in L-glutamate stimulated RBMECs.eEF-2K/eEF-2 should have played an important role in the regulation of P-glycoprotein expression in RBMECs. eEF-2K inhibitor NH125 could serve as an efficacious anti-multidrug resistant agent.

  9. Curcumin inhibits cell growth and invasion and induces apoptosis through down-regulation of Skp2 in pancreatic cancer cells

    Science.gov (United States)

    Su, Jingna; Zhou, Xiuxia; Wang, Lixia; Yin, Xuyuan; Wang, Zhiwei

    2016-01-01

    Natural polyphenol compound curcumin has been found to exhibit its anticancer activity in a variety of human malignancies including pancreatic cancer (PC). However, the underlying mechanism has not been fully understood. Accumulating evidence has demonstrated that Skp2 (S-phase kinase associated protein 2) plays an oncogenic role in the development and progression of human cancers. In this study, we aim to explore the molecular basis of curcumin-induced cell growth inhibition in PC cells.Multiple methods such as CTG assay, Flow cytometry, clonogenic assay, wound healing assay, Transwell invasion assay, Western blotting, and transfection were performed to validate the oncogenic role of curcumin in PC cells. We found that curcumin suppressed cell growth, clonogenic potential, migration and invasion, and induced cell apoptosis and cell cycle arrest. Moreover, we observed thatover-expression of Skp2 significantly promoted cell growth, whereas down-regulation of Skp2 with siRNAs inhibited cell growth. The molecular basis of curcumin-mediated cell growth inhibition we identified is that curcumin significantly suppressed Skp2 expression and subsequently induced p21 expression. These findings suggested thattargeting Skp2 by curcumin could be a promising therapeutic strategy for the treatment of PC patients.

  10. Down-regulation of photosynthesis following girdling, but contrasting effects on fruit set and retention, in two sweet cherry cultivars.

    Science.gov (United States)

    Quentin, A G; Close, D C; Hennen, L M H P; Pinkard, E A

    2013-12-01

    Sweet cherry (Prunus avium) trees were manipulated to analyse the contribution of soluble sugars to sink feedback down-regulation of leaf net CO2 assimilation rate (Anet) and fruit set and quality attributes. Total soluble sugar concentration and Anet were measured in the morning on fully expanded leaves of girdled branches in two sweet cherry cultivars, 'Kordia' and 'Sylvia' characterised typically by low and high crop load, respectively. Leaves on girdled trees had higher soluble sugar concentrations and reduced Anet than leaves on non-girdled trees. Moreover, RuBP carboxylation capacity of Rubisco (Vcmax) and triose-phosphate utilisation (TPU) were repressed in the girdled treatments, despite Jmax remaining unchanged; suggesting an impairment of photosynthetic capacity in response to the girdling treatment. Leaf Anet was negatively correlated to soluble sugars, suggesting a sink feedback regulatory control of photosynthesis. Although there were significantly less fruit set and retained in 'Kordia' than 'Sylvia'; girdling had contrasting effects in each cultivar. Girdling significantly increased fruit set and fruitlet retention in 'Sylvia' cultivar, but had no effect in 'Kordia' cultivar. We propose that low inherent sink demand for photoassimilates of 'Kordia' fruit could have contributed to the low fruit retention rate, since both non-girdled and girdled trees exhibited similar retention rate and that increases in foliar carbohydrates was observed above the girdle. In 'Sylvia' cultivar, the carbohydrate status may be a limiting factor for 'Sylvia' fruit, since girdling improved both fruit set and retention, and leaf soluble solids accumulation. PMID:24189522

  11. Down-regulation of β-catenin Nuclear Localization by Aspirin Correlates with Growth Inhibition of Jurkat Cell Line

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    In this study, we examined the effects of aspirin on the growth rates, subcellar distribution of β-catenin protein, the expression of β-catenin/TCF signaling pathway target gene cyclinD1 mRNA,and cell cycle of Jurkat cell line (Human T-acute lymphoblastic leukemia). Our results showed that the treatment with aspirin inhibited the growth of Jurkat cell line. Jurkat cells treated with 3 mmol/L of aspirin could significantly decrease nuclear localization of β-catenin, and at 5 mmol/L of aspirin,the nuclear localization of β-catenin was undetectable. QRT-PCR showed that the target gene cyclinD1 mRNA expression was gradually decreased with the dosage of aspirin. Aspirin induced G0/G1cell cycle arrest in Jurkat cells. We are led to conclude that aspirin acts through β-catenin-independent mechanisms. The effects of aspirin include down-regulation of β-catenin nuclear localization and G0/G1 cell cycle arrest, which might serve as a means of growth inhibition in aspirin-treated human Jurkat cell line.

  12. Down-Regulation of a Nicotinate Phosphoribosyltransferase Gene, OsNaPRT1, Leads to Withered Leaf Tips.

    Science.gov (United States)

    Wu, Liwen; Ren, Deyong; Hu, Shikai; Li, Gengmi; Dong, Guojun; Jiang, Liang; Hu, Xingming; Ye, Weijun; Cui, Yongtao; Zhu, Li; Hu, Jiang; Zhang, Guangheng; Gao, Zhenyu; Zeng, Dali; Qian, Qian; Guo, Longbiao

    2016-06-01

    Premature leaf senescence affects plant growth and yield in rice. NAD plays critical roles in cellular redox reactions and remains at a sufficient level in the cell to prevent cell death. Although numerous factors affecting leaf senescence have been identified, few involving NAD biosynthetic pathways have been described for plants. Here, we report the cloning and characterization of Leaf Tip Senescence 1 (LTS1) in rice (Oryza sativa), a recessive mutation in the gene encoding O. sativa nicotinate phosphoribosyltransferase (OsNaPRT1) in the NAD salvage pathway. A point mutation in OsNaPRT1 leads to dwarfism and the withered leaf tip phenotype, and the lts1 mutant displays early leaf senescence compared to the wild type. Leaf nicotinate and nicotinamide contents are elevated in lts1, while NAD levels are reduced. Leaf tissue of lts1 exhibited significant DNA fragmentation and H2O2 accumulation, along with up-regulation of genes associated with senescence. The lts1 mutant also showed reduced expression of SIR2-like genes (OsSRT1 and OsSRT2) and increased acetylation of histone H3K9. Down-regulation of OsSRTs induced histone H3K9 acetylation of senescence-related genes. These results suggest that deficiency in the NAD salvage pathway can trigger premature leaf senescence due to transcriptional activation of senescence-related genes. PMID:27208230

  13. Berberine Induces Apoptosis in p53-Null Leukemia Cells by Down-Regulating XIAP at the Post-Transcriptional Level

    Directory of Open Access Journals (Sweden)

    Jian Liu

    2013-11-01

    Full Text Available Background: Berberine exerts anticancer activities both in vitro and in vivo through different mechanisms. However, the underlying molecular mechanisms of berberine induced p53-independent apoptosis remain unclear. Methods: The p53-null leukemia cell line EU-4 cells were exposed to berberine. Then the cell viability and apoptosis were determined. Western blot and PCR were employed to detect the expression of apoptosis related protein, XIAP and MDM2. Small interfering RNA (siRNA was applied to knock down endogenous expression of MDM2 and XIAP. Results: Berberine induced p53-independent, XIAP-mediated apoptotic cell death in p53-null leukemia cells. Treatment with berberine resulted in suppression of XIAP protein in a dose- and time- dependent manner. Berberine induced down-regulation of XIAP protein involving inhibition of MDM2 expression and a proteasome-dependent pathway. Moreover, inhibition of XIAP by berberine or siRNA increased the sensitivity of leukemia cells to doxorubicin-induced apoptosis. Conclusion: Our findings characterize the molecular mechanisms of berberine-induced caspase activation and subsequent apoptosis, and berberine may be a novel candidate inducer of apoptosis in leukemia cells, which normally lack p53 expression.

  14. Down-regulation of Fusarium oxysporum endogenous genes by Host-Delivered RNA interference enhances disease resistance

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    Zongli eHu

    2015-01-01

    Full Text Available Fusarium oxysporum is a devastating pathogen causing extensive yield losses in a variety of crops and development of sustainable, environmentally friendly methods to improve crop resistance is crucial. We have used Host-Derived RNA interference (HD-RNAi technology to partially silence three different genes (FOW2, FRP1 and OPR in the hemi-biotrophic fungus Fusarium oxysporum f. sp. conglutinans. Expression of double stranded RNA molecules targeting fungal pathogen genes was achieved in a number of transgenic Arabidopsis lines. F. oxysporum infecting the transgenic lines displayed substantially reduced mRNA levels on all three targeted genes, with an average of 75%, 83% and 72% reduction for FOW2, FRP1 and OPR respectively. The silencing of pathogen genes had a clear positive effect on the ability of the transgenic lines to fight infection. All transgenic lines displayed enhanced resistance to F. oxysporum with delayed disease symptom development, especially FRP1 and OPR lines. Survival rates after fungal infection were higher in the transgenic lines compared to control wild type plants which consistently showed survival rates of 10%, with FOW2 lines showing 25% survival; FRP1 lines 30-50% survival and FOW2 between 45-70% survival. The down-regulation effect was specific for the targeted genes without unintended effects in related genes. In addition to producing resistant crops, HD-RNAi can provide a useful tool to rapidly screen candidate fungal pathogenicity genes without the need to produce fungal knockout mutants.

  15. Down-regulation of Fusarium oxysporum endogenous genes by Host-Delivered RNA interference enhances disease resistance

    Science.gov (United States)

    Hu, Zongli; Parekh, Urvi; Maruta, Natsumi; Trusov, Yuri; Botella, Jimmy

    2015-01-01

    Fusarium oxysporum is a devastating pathogen causing extensive yield losses in a variety of crops and development of sustainable, environmentally friendly methods to improve crop resistance is crucial. We have used Host-Derived RNA interference (HD-RNAi) technology to partially silence three different genes (FOW2, FRP1 and OPR) in the hemi-biotrophic fungus Fusarium oxysporum f. sp. conglutinans. Expression of double stranded RNA molecules targeting fungal pathogen genes was achieved in a number of transgenic Arabidopsis lines. F. oxysporum infecting the transgenic lines displayed substantially reduced mRNA levels on all three targeted genes, with an average of 75%, 83% and 72% reduction for FOW2, FRP1 and OPR respectively. The silencing of pathogen genes had a clear positive effect on the ability of the transgenic lines to fight infection. All transgenic lines displayed enhanced resistance to F. oxysporum with delayed disease symptom development, especially FRP1 and OPR lines. Survival rates after fungal infection were higher in the transgenic lines compared to control wild type plants which consistently showed survival rates of 10%, with FOW2 lines showing 25% survival; FRP1 lines 30-50% survival and FOW2 between 45-70% survival. The down-regulation effect was specific for the targeted genes without unintended effects in related genes. In addition to producing resistant crops, HD-RNAi can provide a useful tool to rapidly screen candidate fungal pathogenicity genes without the need to produce fungal knockout mutants.

  16. The KCNQ1 potassium channel is down-regulated by ubiquitylating enzymes of the Nedd4/Nedd4-like family

    DEFF Research Database (Denmark)

    Jespersen, Thomas; Membrez, Mathieu; Nicolas, Céline S;

    2007-01-01

    participate in controlling body electrolyte homeostasis. Several regulatory mechanisms of the KCNQ1 channel complexes have been reported, including protein kinase A (PKA)-phosphorylation and beta-subunit interactions. However, the mechanisms controlling the membrane density of KCNQ1 channels have attracted...... less attention. METHODS AND RESULTS: Here we demonstrate that KCNQ1 proteins expressed in HEK293 cells are down-regulated by Nedd4/Nedd4-like ubiquitin-protein ligases. KCNQ1 and KCNQ1/KCNE1 currents were reduced upon co-expression of Nedd4-2, the isoform among the nine members of the Nedd4/Nedd4-like...... by Nedd4-2, an increased ubiquitylation as well as a decreased total level of KCNQ1 proteins were observed in HEK293 cells. Pull-down and co-immunoprecipitation experiments showed that Nedd4-2 interacts with the C-terminal part of KCNQ1. The Nedd4/Nedd4-like-mediated regulation of the KCNQ1 channel...

  17. The Structure, Expression, and Function Prediction of DAZAP2, A Down-Regulated Gene in Multiple Myeloma

    Institute of Scientific and Technical Information of China (English)

    Yiwu Shi; Saiqun Luo; Jianbin Peng; Chenghan Huang; Daren Tan; Weixin Hu

    2004-01-01

    In our previous studies, DAZAP2 gene expression was down-regulated in untreated patients of multiple myeloma (MM). For better studying the structure and function of DAZAP2, a full-length Cdna was isolated from mononuclear cells of a normal human bone marrow, sequenced and deposited to Genbank (AY430097). This sequence has an identical ORF (open reading frame) as the NM_014764 from human testis and the D31767 from human cell line KG-1. Phylogenetic analysis and structure prediction reveal that DAZAP2 homologues are highly conserved throughout evolution and share a polyproline region and several potential SH2/SH3 binding sites. DAZAP2 occurs as a single-copy gene with a four-exon organization. We further noticed that the functional DAZAP2 gene is located on Chromosome 12 and its pseudogene gene is on Chromosome 2 with electronic location of human chromosome in Genbank, though no genetic abnormalities of MM have been reported on Chromosome 12. The ORF of human DAZAP2 encodes a 17-kDa protein, which is highly similar to mouse Prtb. The DAZAP2 protein is mainly localized in cytoplasm with a discrete pattern of punctuated distribution. DAZAP2 may associate with carcinogenesis of MM and participate in yet-to-be identified signaling pathways to regulate proliferation and differentiation of plasma cells.

  18. Down-regulation of CBP80 gene expression as a strategy to engineer a drought-tolerant potato.

    Science.gov (United States)

    Pieczynski, Marcin; Marczewski, Waldemar; Hennig, Jacek; Dolata, Jakub; Bielewicz, Dawid; Piontek, Paulina; Wyrzykowska, Anna; Krusiewicz, Dominika; Strzelczyk-Zyta, Danuta; Konopka-Postupolska, Dorota; Krzeslowska, Magdalena; Jarmolowski, Artur; Szweykowska-Kulinska, Zofia

    2013-05-01

    Developing new strategies for crop plants to respond to drought is crucial for their innovative breeding. The down-regulation of nuclear cap-binding proteins in Arabidopsis renders plants drought tolerant. The CBP80 gene in the potato cultivar Desiree was silenced using artificial microRNAs. Transgenic plants displayed a higher tolerance to drought, ABA-hypersensitive stomatal closing, an increase in leaf stomata and trichome density, and compact cuticle structures with a lower number of microchannels. These findings were correlated with a higher tolerance to water stress. The level of miR159 was decreased, and the levels of its target mRNAs MYB33 and MYB101 increased in the transgenic plants subjected to drought. Similar trends were observed in an Arabidopsis cbp80 mutant. The evolutionary conservation of CBP80, a gene that plays a role in the response to drought, suggests that it is a candidate for genetic manipulations that aim to obtain improved water-deficit tolerance of crop plants. PMID:23231480

  19. Natural product ginsenoside 25-OCH3-PPD inhibits breast cancer growth and metastasis through down-regulating MDM2.

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    Wei Wang

    Full Text Available Although ginseng and related herbs have a long history of utility for various health benefits, their application in cancer therapy and underlying mechanisms of action are not fully understood. Our recent work has shown that 20(S-25-methoxyl-dammarane-3β, 12β, 20-triol (25-OCH(3-PPD, a newly identified ginsenoside from Panax notoginseng, exerts activities against a variety of cancer cells in vitro and in vivo. This study was designed to investigate its anti-breast cancer activity and the underlying mechanisms of action. We observed that 25-OCH(3-PPD decreased the survival of breast cancer cells by induction of apoptosis and G1 phase arrest and inhibited the growth of breast cancer xenografts in vivo. We further demonstrated that, in a dose- and time-dependent manner, 25-OCH(3-PPD inhibited MDM2 expression at both transcriptional and post-translational levels in human breast cancer cells with various p53 statuses (wild type and mutant. Moreover, 25-OCH(3-PPD inhibited in vitro cell migration, reduced the expression of epithelial-to-mesenchymal transition (EMT markers, and prevented in vivo metastasis of breast cancer. In summary, 25-OCH(3-PPD is a potential therapeutic and anti-metastatic agent for human breast cancer through down-regulating MDM2. Further preclinical and clinical development of this agent is warranted.

  20. Perception adapts via top-down regulation to task repetition: A Lotka-Volterra-Haken modeling analysis of experimental data.

    Science.gov (United States)

    Frank, T D

    2016-03-01

    Two experiments are reported in which participants perceived different physical quantities: size and speed. The perceptual tasks were performed in the context of motor performance problems. Participants perceived the size of objects in order to grasp the objects single handed or with both hands. Likewise, participants perceived the speed of a moving treadmill in order to control walking or running at that speed. In both experiments, the perceptual tasks were repeatedly performed by the participants while the to-be-perceived quantity was gradually varied from small to large objects (Experiment 1) and from low to high speeds (Experiment 2). Hysteresis with negative sign was found when participants were not allowed to execute the motor component, that is, when the execution stage was decoupled from the planning stage. No such effect was found in the control condition, when participants were allowed to execute the motor action. Using a Lotka-Volterra-Haken model for two competing neural populations, it is argued that the observations are consistent with the notion that the repetitions induce an adaptation effect of the perceptual system via top-down regulation. Moreover, the amount of synaptic modulation involved in the adaptation is estimated from participant data.

  1. Blocking transforming growth factor- receptor signaling down-regulates transforming growth factor-β1 autoproduction in keloid fibroblasts

    Institute of Scientific and Technical Information of China (English)

    刘伟; 蔡泽浩; 王丹茹; 武小莉; 崔磊; 商庆新; 钱云良; 曹谊林

    2002-01-01

    Objective: To study transforming growth factor-β1(TGF-β1) autoproduction in keloid fibroblasts and theregulation effect of blocking TGF-β intracellular signalingon rhTGF-β1 autoproduction.Methods: Keloid fibroblasts cultured in vitro weretreated with either rhTGF-β1 (5 ng/ml ) or recombinantadenovirus containing a truncated type II TGF-β receptorgene (50 pfu/cell ). Their effects of regulating geneexpression of TGF-β1 and its receptor I and II wereobserved with Northern blot.Results: rhTGF-β1 up-regulated the gene expressionof TGF-β1 and receptor I, but not receptor II. Over-expression of the truncated receptor II down-regulated thegene expression of TGF-β1 and its receptor I, but notreceptor II.Conclusions: TGF-β1 autoproduction was observed inkeloid fibroblasts. Over-expression of the truncated TGF-βreceptor H decreased TGF-β1 autoproduction via blockingTGF-β receptor signaling.

  2. Bmi1 is down-regulated in the aging brain and displays antioxidant and protective activities in neurons.

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    Mohamed Abdouh

    Full Text Available Aging increases the risk to develop several neurodegenerative diseases, although the underlying mechanisms are poorly understood. Inactivation of the Polycomb group gene Bmi1 in mice results in growth retardation, cerebellar degeneration, and development of a premature aging-like phenotype. This progeroid phenotype is characterized by formation of lens cataracts, apoptosis of cortical neurons, and increase of reactive oxygen species (ROS concentrations, owing to p53-mediated repression of antioxidant response (AOR genes. Herein we report that Bmi1 expression progressively declines in the neurons of aging mouse and human brains. In old brains, p53 accumulates at the promoter of AOR genes, correlating with a repressed chromatin state, down-regulation of AOR genes, and increased oxidative damages to lipids and DNA. Comparative gene expression analysis further revealed that aging brains display an up-regulation of the senescence-associated genes IL-6, p19(Arf and p16(Ink4a, along with the pro-apoptotic gene Noxa, as seen in Bmi1-null mice. Increasing Bmi1 expression in cortical neurons conferred robust protection against DNA damage-induced cell death or mitochondrial poisoning, and resulted in suppression of ROS through activation of AOR genes. These observations unveil that Bmi1 genetic deficiency recapitulates aspects of physiological brain aging and that Bmi1 over-expression is a potential therapeutic modality against neurodegeneration.

  3. Down-regulation of miR-133a as a poor prognosticator in non-small cell lung cancer.

    Science.gov (United States)

    Wang, Yuzhou; Li, Jinmei; Chen, Hongming; Mo, Yanli; Ye, Haiyin; Luo, Yiping; Guo, Kangwen; Mai, Zongjiong; Zhang, Ying; Chen, Baoying; Zhou, Yijin; Yang, Zhixiong

    2016-10-15

    miR-133a has been demonstrated to play an important role in tumor progression. The aim of present study was to analyze the correlation between miR-133a expression level and clinicopathologic features and its prognostic significance in non-small cell lung cancer (NSCLC). The expression of miR-133a in 104 pairs of human lung cancer tissues and adjacent normal lung tissues were analyzed by qRT-PCR. Here we show that miR-133a was down-regulated in NSCLC. The levels of miR-133a were negatively correlated with the status of N classification (N0-N1 vs. N2-N3, P=0.000), clinical stage (I-II vs. III-IV, P=0.010) and MMP-14 expression (High vs. Low, P=0.012). The patients with low miR-133a expression had shorter survival time than those with high miR-133a expression. Multivariate analysis indicated that the level of miR-133a expression was an independent prognostic indicator (P=0.012) for the survival of patients with NSCLC. In conclusion, decreased expression of miR-133a might be a potential unfavorable prognostic factor for patients with NSCLC, and further studies would be needed to prove our findings.

  4. An anti-inflammatory oligopeptide produced by Entamoeba histolytica down-regulates the expression of pro-inflammatory chemokines.

    Science.gov (United States)

    Utrera-Barillas, Dolores; Velazquez, Juan R; Enciso, Antonio; Cruz, Samira Muñoz; Rico, Guadalupe; Curiel-Quesada, Everardo; Teran, Luis M; Kretschmer, Roberto R

    2003-10-01

    Axenically grown Entamoeba histolytica produces a pentapeptide (Met-Gln-Cys-Asn-Ser) with anti-inflammatory properties that, among others, inhibits the in vitro and in vivo locomotion of human monocytes, sparing polymorphonuclear leucocytes from this effect [hence the name originally given. Monocyte Locomotion Inhibitory Factor (MLIF)]. A synthetic construct of this peptide displays the same effects as the native material. We now added MLIF to resting and PMA-stimulated cells of a human monocyte cell line and measured the effect upon mRNA and protein expression of pro-inflammatory chemokines (RANTES, IP-10, MIP-1alpha, MIP-1beta, MCP-1, IL-8, I-309 and lymphotactin) and the shared CC receptor repertoire. The constitutive expression of these chemokines and the CC receptors was unaffected, whereas induced expression of MIP-1alpha, MIP-1beta, and I-309, and that of the CCR1 receptor--all involved in monocyte chemotaxis--was significantly inhibited by MLIF. This suggests that the inhibition of monocyte functions by MLIF may not only be exerted directly on these cells, but also--and perhaps foremost--through a conglomerate down-regulation of endogenous pro-inflammatory chemokines.

  5. Galectin-4 expression is down-regulated in response to autophagy during differentiation of rat trophoblast cells.

    Science.gov (United States)

    Arikawa, Tomohiro; Liao, Shengjun; Shimada, Hiroki; Inoue, Tomoki; Sakata-Haga, Hiromi; Nakamura, Takanori; Hatta, Toshihisa; Shoji, Hiroki

    2016-01-01

    Placental development and trophoblast invasion of the maternal endometrium establish the maternal-fetal interface, which is critical for the developing embryo and fetus. Herein we show that overexpression of Galectin-4 (Gal-4) during trophoblast differentiation inhibited the enlargement of Rcho-1 cells (a model for rat trophoblast differentiation) and promoted cell-cell adhesion, whereas trophoblast specific markers and MMP-9 activity were not affected. In the rat placenta, microtubule associated protein 1 light chain 3 alpha (LC3) protein, an autophagy marker, is highly expressed on the maternal side of the decidua where Gal-4 expression is weak. In vitro assays showed that the expression of trophoblast-specific differentiation markers was reduced by 3-Methyladenine (3-MA) and Bafilomycin A1, known as autophagy inhibitors, compared to control cells. Furthermore, Gal-4 expression in Rcho-1 cells, which is normally down-regulated during differentiation, was not attenuated in the presence of autophagy inhibitors, suggesting that autophagy is upstream of Gal-4 expression. We herein describe a possible mechanism by which autophagy regulates trophoblast differentiation via regulation of Gal-4 expression in order to establish the maternal-fetal interface. PMID:27572741

  6. Top-down regulation, climate and multi-decadal changes in coastal zoobenthos communities in two Baltic Sea areas.

    Directory of Open Access Journals (Sweden)

    Jens Olsson

    Full Text Available The structure of many marine ecosystems has changed substantially during recent decades, as a result of overexploitation, climate change and eutrophication. Despite of the apparent ecological and economical importance of coastal areas and communities, this aspect has received relatively little attention in coastal systems. Here we assess the temporal development of zoobenthos communities in two areas on the Swedish Baltic Sea coast during 30 years, and relate their development to changes in climate, eutrophication and top-down regulation from fish. Both communities show substantial structural changes, with a decrease in marine polychaetes and species sensitive to increased water temperatures. Concurrently, opportunistic species tolerant to environmental perturbation have increased in abundance. Species composition show a similar temporal development in both communities and significant changes in species composition occurred in both data sets in the late 1980s and early 1990s. The change in species composition was associated with large scale changes in climate (salinity and water temperature and to the structure of the local fish community, whereas we found no effects of nutrient loading or ambient nutrient concentrations. Our results suggest that these coastal zoobenthos communities have gone through substantial structural changes over the last 30 years, resulting in communities of different species composition with potentially different ecological functions. We hence suggest that the temporal development of coastal zoobenthos communities should be assessed in light of prevailing climatic conditions considering the potential for top-down effects exerted by local fish communities.

  7. Altered Lignin Biosynthesis Improves Cellulosic Bioethanol Production in Transgenic Maize Plants Down-Regulated for Cinnamyl Alcohol Dehydrogenase

    Institute of Scientific and Technical Information of China (English)

    Silvia Fornalé; Pere Puigdomènech; Joan Rigau; David Caparrós-Ruiz; Montserrat Capellades; Antonio Encina; Kan Wang; Sami Irar; Catherine Lapierre; Katia Ruel; Jean-Paul Joseleau; Jordi Berenguer

    2012-01-01

    Cinnamyl alcohol dehydrogenase(CAD)is a key enzyme involved in the last step of monolignol biosynthesis.The effect of CAD down-regulation on lignin production was investigated through a transgenic approach in maize.Transgenic CAD-RNAi plants show a different degree of enzymatic reduction depending on the analyzed tissue and show alterations in cell wall composition.Cell walls of CAD-RNAi stems contain a lignin polymer with a slight reduction in the S-to-G ratio without affecting the total lignin content.In addition,these cell walls accumulate higher levels of cellulose and arabinoxylans.In contrast,cell walls of CAD-RNAi midribs present a reduction in the total lignin content and of cell wall polysaccharides.In vitro degradability assays showed that,although to a different extent,the changes induced by the repression of CAD activity produced midribs and stems more degradable than wild-type plants.CAD-RNAi plants grown in the field presented a wild-type phenotype and produced higher amounts of dry biomass.Cellulosic bioethanol assays revealed that CAD-RNAi biomass produced higher levels of ethanol compared to wild-type,making CAD a good target to improve both the nutritional and energetic values of maize lignocellulosic biomass.

  8. Galectin-1 is expressed in early-type neural progenitor cells and down-regulates neurogenesis in the adult hippocampus

    Directory of Open Access Journals (Sweden)

    Imaizumi Yoichi

    2011-01-01

    Full Text Available Abstract Background In the adult mammalian brain, neural stem cells (NSCs proliferate in the dentate gyrus (DG of the hippocampus and generate new neurons throughout life. A multimodal protein, Galectin-1, is expressed in neural progenitor cells (NPCs and implicated in the proliferation of the NPCs in the DG. However, little is known about its detailed expression profile in the NPCs and functions in adult neurogenesis in the DG. Results Our immunohistochemical and morphological analysis showed that Galectin-1 was expressed in the type 1 and 2a cells, which are putative NSCs, in the subgranular zone (SGZ of the adult mouse DG. To study Galectin-1's function in adult hippocampal neurogenesis, we made galectin-1 knock-out mice on the C57BL6 background and characterized the effects on neurogenesis. In the SGZ of the galectin-1 knock-out mice, increased numbers of type 1 cells, DCX-positive immature progenitors, and NeuN-positive newborn neurons were observed. Using triple-labeling immunohistochemistry and morphological analyses, we found that the proliferation of the type-1 cells was increased in the SGZ of the galectin-1 knock-out mice, and we propose that this proliferation is the mechanism for the net increase in the adult neurogenesis in these knock-out mice DG. Conclusions Galectin-1 is expressed in the neural stem cells and down-regulates neurogenesis in the adult hippocampus.

  9. Cisplatin and ultra-violet-C synergistically down-regulate receptor tyrosine kinases in human colorectal cancer cells

    Directory of Open Access Journals (Sweden)

    Kawaguchi Junji

    2012-07-01

    Full Text Available Abstract Background Platinum-containing anti-cancer drugs such as cisplatin are widely used for patients with various types of cancers, however, resistance to cisplatin is observed in some cases. Whereas we have recently reported that high dose UV-C (200 J/m² induces colorectal cancer cell proliferation by desensitization of EGFR, which leads oncogenic signaling in these cells, in this study we investigated the combination effect of low dose cisplatin (10 μM and low dose UV-C (10 J/m² on cell growth and apoptosis in several human colorectal cancer cells, SW480, DLD-1, HT29 and HCT116. Results The combination inhibited cell cycle and colony formation, while either cisplatin or UV-C alone had little effect. The combination also induced apoptosis in these cells. In addition, the combination caused the downregulation of EGFR and HER2. Moreover, UV-C alone caused the transient internalization of the EGFR, but with time EGFR recycled back to the cell surface, while cisplatin did not affect its localization. Surprisingly, the combination caused persistent internalization of the EGFR, which results in the lasting downregulation of the EGFR. Conclusions The combination of low dose cisplatin and low dose UV-C synergistically exerted anti-cancer effect by down-regulating RTK, such as EGFR and HER2. These findings may provide a novel strategy for the treatment of patients with colorectal cancer.

  10. A novel method of preparing metallic Janus silica particles using supercritical carbon dioxide.

    Science.gov (United States)

    Yang, Qiuyan; de Vries, Marcel H; Picchioni, Francesco; Loos, Katja

    2013-11-01

    In this study, we demonstrate a novel fabrication method to prepare metallic Janus silica particles by embedding nanosized silica particles on a spherical polystyrene (PS) substrate in supercritical carbon dioxide (sc CO2), followed by labelling with gold nanoparticles on the exposed part of the silica colloids. To this end, three main types of Janus particles displaying two distinct surfaces are produced by recovering silica from the polystyrene template. Embedment of particles into the PS template in sc CO2 allows for precise control of the degree of embedding of particles and subsequent modification of the partially exposed particle surface. The embedding degree, as well as the final Janus balance, can be varied over a wide range through control of pressure, temperature, or treatment time of sc CO2. Hierarchical PS-silica composites and embedment are evaluated by scanning electron microscopy (SEM). Partial surface modification with gold nanoparticles is investigated by transmission electron microscopy (TEM). With this method various functionalized Janus particles with tuneable properties can be prepared by adjusting various surface modifiers and polymer substrates in the future. PMID:24056955

  11. Passive vibration damping of carbon fiber reinforced plastic with PZT particles and SMA powder

    Science.gov (United States)

    Jung, Jaemin; Lee, Woo Il; Lee, Dasom; Park, Sungho; Moon, Sungnam

    2016-04-01

    Carbon fiber reinforced plastic (CFRP) has been used various industrial fields, because of high strength, light weight, corrosion resistance and other properties. In this study, lead zirconate titanate (PZT) ceramic particles which is one of typical piezoelectric material and shape memory alloy powder dispersed in CFRP laminate in order to improve the vibration damping by dissipating vibration energy quickly. The loss factor (tanδ) is measured in Dynamic mechanical analyzer (DMA) which is used to measure the viscoelastic behavior of a material to verify the change in vibration damping. The results show that there exists difference on vibration damping ability between CFRP with PZT ceramic particles and CFRP with SMA powder.

  12. Effect of Particle Density on the Aligned Growth of Carbon Nanotubes

    Institute of Scientific and Technical Information of China (English)

    WANG Sheng-gao; WANG Jian-hua; HAN Jian-jun

    2004-01-01

    Aligned carbon nanotubes (CNTs) were prepared on Ni-coated Ni substrate by microwave plasma chemical vapor deposition (MWPCVD) with a mixture of methane and hydrogen gases at temperature of 550℃.The experimental results show a direct correlation between the alignment of CNTs and the density of the catalyst particles at low temperature.When the particle density is high enough,among CNTs there are strong interactions that can inhibit CNTs from growing randomly.The crowding effect among dense CNTs results in the aligned growth of CNTs at low temperature.

  13. Chemically Robust Carbon Particles in Peat from the Tunguska Impact Site

    Science.gov (United States)

    Hough, R. M.; Gilmour, I.; Newton, J.; Arden, J.; Pillinger, C. T.

    1995-09-01

    The Tunguska impact event of 1908 caused the destruction of a large forested area but left no impact crater. It was interpreted to have exploded in mid-air and thus would disperse material in a fireball over a wide geographical area. Several attempts have been made to locate particles associated with the impact in materials such as tree resin (1) and even in Antarctic snow (2). One of us (JN) attended an expedition to the Tunguska impact area and collected samples of peat from a depth of 60 cm which is thought to be the level in the peat which holds the impact horizon and indeed contains charred vegetation. The peat was subjected to standard demineralization procedures using mineral and oxidizing acids to destroy all but the most resistant mineral phases. An emphasis was placed on the chromic acid treatment to remove organic carbon as the peat was inevitably of extremely high organic content but perchloric acid was also used to oxidize graphite. The residue after treatment has subsequently been examined using a scanning electron microscope (Jeol JSM-820I at 30kv) with a Kevex system to obtain an energy dispersion scan and subjected to stepped combustion to determine the carbon abundance and isotopic composition. The SEM revealed the predominance in the residue of chromium containing phases possibly as a result of the extensive chromic acid treatments but several very pure carbon-rich particles were also observed. These carbon particles were anhedral and up to 15 micrometers in size. Due to the nature of the acid treatment performed upon this sample only a very robust form of carbon could survive and the most likely mineral is diamond. Further analyses using a transmission electron microscope and selected are electron diffraction will be performed to resolve the true mineralogy of these carbon particles. Stepped heating experiments on the acid resistant residue in conjunction with static mass spectrometry (3) has been used to give both carbon and nitrogen contents

  14. Combustion characteristics of water-insoluble elemental and organic carbon in size selected ambient aerosol particles

    Directory of Open Access Journals (Sweden)

    K. Wittmaack

    2005-04-01

    Full Text Available Combustion of elemental carbon (EC and organic carbon (OC contained in ambient aerosol matter was explored using scanning electron microscopy (SEM in combination with energy dispersive X-ray analysis (EDX. To ease identification of the particles of interest and to avoid or at least reduce interaction with simultaneously sampled inorganic oxides and salts, the approach used in this work differed in two ways from commonly applied procedures. First, rather than using a mixture of particles of vastly different sizes, as in PM10 or PM2.5, aerosol matter was collected in a 5-stage impactor. Second, the water soluble fraction of the collected matter was removed prior to analysis. Diesel soot particles, which appeared in the well-known form of chain-type aggregates, constituted the major fraction of EC. In contrast, OC containing particles were observed in a variety of shapes, including a sizable amount of bioaerosol matter appearing mostly in the size range above about 1 µm. During heating in ambient air for 1 h, diesel soot particles were found to be stable up to 480°C, but complete combustion occurred in a narrow temperature interval between about 490 and 510°C. After diesel soot combustion, minute quantities of ''ash'' were observed in the form of aggregated tiny particles with sizes less than 10 nm. These particles could be due to elemental or oxidic contaminants of diesel soot. Combustion of OC was observed over a wide range of temperatures, from well below 200°C to at least 500°C. Incompletely burnt bioaerosol matter was still found after heating to 600°C. The results imply that the EC fraction in aerosol matter can be overestimated significantly if the contribution of OC to a thermogram is not well separated.

  15. Combustion characteristics of water-insoluble elemental and organic carbon in size selected ambient aerosol particles

    Directory of Open Access Journals (Sweden)

    K. Wittmaack

    2005-01-01

    Full Text Available Combustion of elemental carbon (EC and organic carbon (OC contained in ambient aerosol matter was explored using scanning electron microscopy (SEM in combination with energy dispersive X-ray analysis (EDX. To ease identification of the particles of interest and to avoid or at least reduce interaction with simultaneously sampled inorganic oxides and salts, the approach used in this work differed in two ways from commonly applied procedures. First, rather than using a mixture of particles of vastly different sizes, as in PM10 or PM2.5, aerosol matter was collected in a 5-stage impactor. Second, the water soluble fraction of the collected matter was removed prior to analysis. Diesel soot particles, which appeared in the well-known form of chain-type aggregates, constituted the major fraction of EC. In contrast, OC containing particles were observed in a variety of shapes, including a sizable amount of bioaerosol matter appearing mostly in the size range above about 1 µm. During heating in ambient air for 1h, diesel soot particles were found to be stable up to 470°C, but complete combustion occurred in a narrow temperature interval between about 480 and 510°C. After diesel soot combustion, minute quantities of 'ash' were observed in the form of aggregated tiny particles with sizes less than 10 nm. These particles could be due to elemental or oxidic contaminants of diesel soot. Combustion of OC was observed over a wide range of temperatures, from well below 200°C to at least 500°C. Incompletely burnt bioaerosol matter was still found after heating to 600°C. The results imply that the EC fraction in aerosol matter can be overestimated significantly if the contribution of OC to a thermogram is not well separated.

  16. How do changes in bulk soil organic carbon content affect carbon concentrations in individual soil particle fractions?

    Science.gov (United States)

    Yang, X. M.; Drury, C. F.; Reynolds, W. D.; Yang, J. Y.

    2016-06-01

    We test the common assumption that organic carbon (OC) storage occurs on sand-sized soil particles only after the OC storage capacity on silt- and clay-sized particles is saturated. Soil samples from a Brookston clay loam in Southwestern Ontario were analysed for the OC concentrations in bulk soil, and on the clay (clay, but this maximum was far greater than the maximum predicted by established C sequestration models. In addition, significant increases in OC associated with sand occurred when the bulk soil OC concentration exceeded 30 g C kg‑1, but this increase occurred when the OC concentration on silt + clay was still far below the predicted storage capacity for silt and clay fractions. Since the OC concentrations in all fractions of Brookston clay loam soil continued to increase with increasing C (bulk soil OC content) input, we concluded that the concept of OC storage capacity requires further investigation.

  17. Silencing of microRNA-155 in mice during acute inflammatory response leads to derepression of c/ebp Beta and down-regulation of G-CSF

    DEFF Research Database (Denmark)

    Worm, Jesper; Stenvang, Jan; Petri, Andreas;

    2009-01-01

    -stimulating factor (G-CSF), a central regulator of granulopoiesis during inflammatory responses. Consistent with these data, we show that silencing of miR-155 in LPS-treated mice by systemically administered LNA-antimiR results in derepression of the c/ebp Beta isoforms and down-regulation of G-CSF expression...

  18. CD3 gamma contains a phosphoserine-dependent di-leucine motif involved in down-regulation of the T cell receptor

    DEFF Research Database (Denmark)

    Dietrich, J; Hou, X; Wegener, A M;

    1994-01-01

    Several cell surface receptors including the T cell receptor (TCR) are phosphorylated and down-regulated following activation of protein kinase C (PKC). Among other substrates the activated PKC in T cells phosphorylates the CD3 gamma subunit of the TCR. To investigate the role of CD3 gamma...... phosphorylation in PKC-mediated TCR down-regulation, point mutated CD3 gamma cDNA was transfected into the CD3 gamma-negative T cell line JGN and CD3 gamma transfectants were analysed. Phosphorylation at S126 but not S123 in the cytoplasmic tail of CD3 gamma was required for PKC-mediated down-regulation of the...... TCR. Furthermore, analysis of a series of CD3 gamma truncation mutants indicated that in addition to S126 phosphorylation a motif C-terminal of S126 was required for TCR down-regulation. Point mutation analyses confirmed this observation and demonstrated that a membrane-proximal di-leucine motif (L131...

  19. Resolvin D1 Protects Lipopolysaccharide-induced Acute Kidney Injury by Down-regulating Nuclear Factor-kappa B Signal and Inhibiting Apoptosis

    Directory of Open Access Journals (Sweden)

    Yu-Liang Zhao

    2016-01-01

    Conclusion: In LPS-induced AKI, RvD1 could decrease TNF-α level, ameliorate kidney pathological injury, protect kidney function, and improve animal survival by down-regulating NF-κB inflammatory signal as well as inhibiting renal cell apoptosis.

  20. Antisense down-regulation of strawberry endo-beta (1,4)-glucanase genes does not prevent fruit softening during ripening

    NARCIS (Netherlands)

    Palomer, X.; Llop-Tous, I.; Vendrell, M.; Krens, F.A.; Schaart, J.G.; Boone, M.J.; Valk, van der H.C.P.M.; Salentijn, E.M.J.

    2006-01-01

    Strawberry (Fragaria × ananassa Duch.) fruit softening during ripening is associated with the overlapping presence of two divergent endo-ß-(1,4)-glucanases (EC 3.2.1.4; EGases), Cel1 and Cel2. Antisense down-regulation of both genes was performed to assess the precise role of these endo-ß-(1,4)-gluc

  1. The non-structural protein Nsp2TF of porcine reproductive and respiratory syndrome virus down-regulates the expression of Swine Leukocyte Antigen class I.

    Science.gov (United States)

    Cao, Qian M; Subramaniam, Sakthivel; Ni, Yan-Yan; Cao, Dianjun; Meng, Xiang-Jin

    2016-04-01

    Porcine reproductive and respiratory syndrome virus (PRRSV) is arguably the most economically-important global swine pathogen. Here we demonstrated that PRRSV down-regulates Swine Leukocyte Antigen class I (SLA-I) expression in porcine alveolar macrophages, PK15-CD163 cells and monocyte-derived dendritic cells. To identify the viral protein(s) involved in SLA-I down-regulation, we tested all 22 PRRSV structural and non-structural proteins and identified that Nsp1α and Nsp2TF, and GP3 significantly down-regulated SLA-I expression with Nsp2TF showing the greatest effect. We further generated a panel of mutant viruses in which the Nsp2TF protein synthesis was abolished, and found that the two mutants with disrupted -2 ribosomal frameshifting elements and additional stop codons in the TF domain were unable to down-regulate SLA-I expression. Additionally we demonstrated that the last 68 amino acids of TF domain in Nsp2TF are critical for this function. Collectively, the results indicate a novel function of Nsp2TF in negative modulation of SLA-I expression. PMID:26895249

  2. Down-regulation of MHC Class I by the Marek's Disease Virus (MDV) UL49.5 Gene Product Mildly Affects Virulence in a Haplotype-specific Fashion

    Science.gov (United States)

    Marek’s disease is a devastating neoplastic disease of chickens caused by gallid herpesvirus 2 or Marek’s disease virus (MDV), which is characterized by massive visceral tumors, immune suppression, neurologic syndromes, and peracute deaths. It has been reported that MDV down-regulates surface expre...

  3. Toluene vapor capture by activated carbon particles in a dual gas-solid cyclone system.

    Science.gov (United States)

    Lim, Yun Hui; Ngo, Khanh Quoc; Park, Young Koo; Jo, Young Min

    2012-08-01

    Capturing of odorous compounds such as toluene vapor by a particulate-activated carbon adsorbent was investigated in a gas-solid cyclone, which is one type of mobile beds. The test cyclone was early modified with the post cyclone (PoC) and a spiral flow guide to the vortex finder. The proposed process may contribute to the reduction of gases and dust from industrial exhausts, especially when dealing with a low concentration of odorous elements and a large volume ofdust flow. In this device, the toluene capturing efficiency at a 400 ppm concentration rose up to 77.4% when using activated carbon (AC) particles with a median size of 27.03 microm. A maximum 96% of AC particles could be collected for reuse depending on the size and flow rate. The AC regenerated via thermal treatment showed an adsorption potential up to 66.7% throughout repeated tests.

  4. How do changes in bulk soil organic carbon content affect carbon concentrations in individual soil particle fractions?

    Science.gov (United States)

    Yang, X M; Drury, C F; Reynolds, W D; Yang, J Y

    2016-01-01

    We test the common assumption that organic carbon (OC) storage occurs on sand-sized soil particles only after the OC storage capacity on silt- and clay-sized particles is saturated. Soil samples from a Brookston clay loam in Southwestern Ontario were analysed for the OC concentrations in bulk soil, and on the clay (<2 μm), silt (2-53 μm) and sand (53-2000 μm) particle size fractions. The OC concentrations in bulk soil ranged from 4.7 to 70.8 g C kg(-1) soil. The OC concentrations on all three particle size fractions were significantly related to the OC concentration of bulk soil. However, OC concentration increased slowly toward an apparent maximum on silt and clay, but this maximum was far greater than the maximum predicted by established C sequestration models. In addition, significant increases in OC associated with sand occurred when the bulk soil OC concentration exceeded 30 g C kg(-1), but this increase occurred when the OC concentration on silt + clay was still far below the predicted storage capacity for silt and clay fractions. Since the OC concentrations in all fractions of Brookston clay loam soil continued to increase with increasing C (bulk soil OC content) input, we concluded that the concept of OC storage capacity requires further investigation. PMID:27251365

  5. Online single particle measurements of black carbon coatings, structure and optical properties

    Science.gov (United States)

    Allan, James; Liu, Dantong; Taylor, Jonathan; Flynn, Michael; Williams, Paul; Morgan, William; Whitehead, James; Alfarra, Rami; McFiggans, Gordon; Coe, Hugh

    2016-04-01

    The impacts of black carbon on meteorology and climate remain a major source of uncertainty, owing in part to the complex relationship between the bulk composition of the particulates and their optical properties. A particular complication stems from how light interacts with particles in response to the microphysical configuration and any 'coatings', i.e. non-black carbon material that is either co-emitted or subsequently obtained through atmospheric processing. This may cause the particle to more efficiently absorb or scatter light and may even change the sign of its radiative forcing potential. While much insight has been gained through measurements of bulk aerosol properties, either while suspended or after collection on a filter or impactor substrate, this does not provide a complete picture and thus may not adequately constrain the system. Here we present an overview of recent work to better constrain the properties of black carbon using online, in situ measurements of single particles, primarily using a Single Particle Soot Photometer (SP2). We have developed novel methods of inverting the data produced and combining the different metrics derived so as to give the most effective insights into black carbon sources, processes and properties. We have also used this measurement in conjunction with other instruments (sometimes in series) and used the data to challenge many commonly used models of optical properties such as core-shell Mie, Rayleigh-Debeye-Gans and effective medium. This work has been carried out in a variety of atmospheric environments and with laboratory-produced soots, e.g. from a diesel engine rig. Highlights include the finding that with real-world atmospheric aerosols, bulk optical measurements may be insufficient to derive brown carbon parameters without detailed morphological data. We also show that the enhancement of absorption for both ambient and laboratory generated particles only occurs after the coating mass fraction reaches a certain

  6. Metformin suppresses CYP1A1 and CYP1B1 expression in breast cancer cells by down-regulating aryl hydrocarbon receptor expression

    Energy Technology Data Exchange (ETDEWEB)

    Do, Minh Truong; Kim, Hyung Gyun; Tran, Thi Thu Phuong; Khanal, Tilak; Choi, Jae Ho [Department of Toxicology, College of Pharmacy, Chungnam National University, Daejeon (Korea, Republic of); Chung, Young Chul [Department of Food Science and Culinary, International University of Korea, Jinju (Korea, Republic of); Jeong, Tae Cheon, E-mail: taecheon@ynu.ac.kr [College of Pharmacy, Yeungnam University, Gyeongsan (Korea, Republic of); Jeong, Hye Gwang, E-mail: hgjeong@cnu.ac.kr [Department of Toxicology, College of Pharmacy, Chungnam National University, Daejeon (Korea, Republic of)

    2014-10-01

    Induction of cytochrome P450 (CYP) 1A1 and CYP1B1 by environmental xenobiotic chemicals or endogenous ligands through the activation of the aryl hydrocarbon receptor (AhR) has been implicated in a variety of cellular processes related to cancer, such as transformation and tumorigenesis. Here, we investigated the effects of the anti-diabetes drug metformin on expression of CYP1A1 and CYP1B1 in breast cancer cells under constitutive and inducible conditions. Our results indicated that metformin down-regulated the expression of CYP1A1 and CYP1B1 in breast cancer cells under constitutive and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced conditions. Down-regulation of AhR expression was required for metformin-mediated decreases in CYP1A1 and CYP1B1 expression, and the metformin-mediated CYP1A1 and CYP1B1 reduction is irrelevant to estrogen receptor α (ERα) signaling. Furthermore, we found that metformin markedly down-regulated Sp1 protein levels in breast cancer cells. The use of genetic and pharmacological tools revealed that metformin-mediated down-regulation of AhR expression was mediated through the reduction of Sp1 protein. Metformin inhibited endogenous AhR ligand-induced CYP1A1 and CYP1B1 expression by suppressing tryptophan-2,3-dioxygenase (TDO) expression in MCF-7 cells. Finally, metformin inhibits TDO expression through a down-regulation of Sp1 and glucocorticoid receptor (GR) protein levels. Our findings demonstrate that metformin reduces CYP1A1 and CYP1B1 expression in breast cancer cells by down-regulating AhR signaling. Metformin would be able to act as a potential chemopreventive agent against CYP1A1 and CYP1B1-mediated carcinogenesis and development of cancer. - Graphical abstract: Schematic of the CYP1A1 and CYP1B1 gene regulation by metformin. - Highlights: • Metformin inhibits CYP1A1 and CYP1B1 expression. • Metformin down-regulates the AhR signaling. • Metformin reduces Sp1 protein expression. • Metformin suppresses TDO expression.

  7. Microstructural characteristics of an AZ91 matrix-glassy carbon particle composite

    Energy Technology Data Exchange (ETDEWEB)

    Olszowka-Myalska, Anita; Myalski, Jerzy; Botor-Probierz, Agnieszka [Faculty of Materials Sciences and Metallurgy, Silesian University of Technology (Poland)

    2010-07-15

    This paper presents the results of a microstructural investigation of a new type of ultralight glassy carbon particles (C{sub p})-AZ91 magnesium alloy matrix composite manufactured by the powder metallurgy method. Glassy C{sub p} with unmodified surfaces and surfaces modified with SiO{sub 2} amorphous nanocoating were used in the experiment. The composite microstructure, with an emphasis given on the interface, was characterized by scanning electron microscope (SEM), TEM, and HRTEM microscopy. Uniform distribution of the particles in the matrix and their good bonding with the metal matrix were observed. A continuous very thin MgO oxide layer containing needle-like Al{sub 2}MgO{sub 4} phase was detected at the glassy carbon-AZ91 interface. An increase of aluminum concentration at the interface as a result of Mg and Al diffusion into the SiO{sub 2} nanolayer was observed in the case of particles modified with SiO{sub 2}. Crystalline phases containing carbon were not detected at the interface. (Abstract Copyright [2010], Wiley Periodicals, Inc.)

  8. Energy loss of tens keV charged particles traveling in the hot dense carbon plasma

    Science.gov (United States)

    Fu, ZhenGuo; Wang, ZhiGang; He, Bin; Li, DaFang; Zhang, Ping

    2016-08-01

    The energy loss of charged particles, including electrons, protons, and α-particles with tens keV initial energy E 0, traveling in the hot dense carbon (C) plasma for densities from 2.281 to 22.81 g/cm3 and temperatures from 400 to 1500 eV is systematically and quantitatively studied by using the dimensional continuation method. The behaviors of different charged particles are readily distinguishable from each other. Firstly, because an ion is thousands times heavier than an electron, the penetration distance of the electron is much longer than that of proton and α-particle traveling in the plasma. Secondly, most energy of electron projectile with E 0 < 100 keV deposits into the electron species of C plasma, while for the cases of proton and α-particle with E 0 < 100 keV, about more than half energy transfers into the ion species of C plasma. A simple decreasing law of the penetration distance as a function of the plasma density is fitted, and different behaviors of each projectile particle can be clearly found from the fitted data. We believe that with the advanced progress of the present experimental technology, the findings shown here could be confirmed in ion-stopping experiments in the near future.

  9. Particle number scaling for diffusion-induced dissipation in graphene and carbon nanotube nanomechanical resonators

    Science.gov (United States)

    Rhén, Christin; Isacsson, Andreas

    2016-03-01

    When a contaminant diffuses on the surface of a nanomechanical resonator, the motions of the two become correlated. Despite being a high-order effect in the resonator-particle coupling, such correlations affect the system dynamics by inducing dissipation of the resonator energy. Here, we consider this diffusion-induced dissipation in the cases of multiple particles adsorbed on carbon nanotube and graphene resonators. By solving the stochastic equations of motion, we simulate the ringdown of the resonator, in order to determine the resonator energy decay rate. We find two different scalings with the number of adsorbed particles K and particle mass m . In the regime where the adsorbates are inertially trapped at an antinode of vibration, the dissipation rate Γ scales with the total adsorbed mass Γ ∝K m . In contrast, in the regime where particles diffuse freely over the resonator, the dissipation rate scales as the product of the total adsorbed mass and the individual particle mass: Γ ∝K m2 .

  10. Apigenin suppresses migration and invasion of transformed cells through down-regulation of C-X-C chemokine receptor 4 expression

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Lei; Kuang, Lisha; Hitron, John Andrew; Son, Young-Ok; Wang, Xin; Budhraja, Amit [Graduate Center for Toxicology, College of Medicine, University of Kentucky, Lexington, KY 40536 (United States); Lee, Jeong-Chae [Graduate Center for Toxicology, College of Medicine, University of Kentucky, Lexington, KY 40536 (United States); Institute of Oral Biosciences and BK21 Program, Research Center of Bioactive Materials, Chonbuk National University, Jeonju 561-756 (Korea, Republic of); Pratheeshkumar, Poyil [Graduate Center for Toxicology, College of Medicine, University of Kentucky, Lexington, KY 40536 (United States); Chen, Gang [Department of Internal Medicine, University of Kentucky College of Medicine, Lexington, KY 40536 (United States); Zhang, Zhuo [Graduate Center for Toxicology, College of Medicine, University of Kentucky, Lexington, KY 40536 (United States); Luo, Jia [Department of Internal Medicine, University of Kentucky College of Medicine, Lexington, KY 40536 (United States); Shi, Xianglin, E-mail: xshi5@email.uky.edu [Graduate Center for Toxicology, College of Medicine, University of Kentucky, Lexington, KY 40536 (United States)

    2013-10-01

    Environmental exposure to arsenic is known to cause various cancers. There are some potential relationships between cell malignant transformation and C-X-C chemokine receptor type 4 (CXCR4) expressions. Metastasis, one of the major characteristics of malignantly transformed cells, contributes to the high mortality of cells. CXCR4 and its natural chemokine ligand C-X-C motif ligand 12 (CXCL12) play a critical role in metastasis. Therefore, identification of nutritional factors which are able to inhibit CXCR4 is important for protection from environmental arsenic-induced carcinogenesis and for abolishing metastasis of malignantly transformed cells. The present study demonstrates that apigenin (4′,5,7-trihydroxyflavone), a natural dietary flavonoid, suppressed CXCR4 expression in arsenic-transformed Beas-2B cells (B-AsT) and several other types of transformed/cancer cells in a dose- and time-dependent manner. Neither proteasome nor lysosome inhibitor had any effect in reducing the apigenin-induced down-regulation of CXCR4, indicating that apigenin-induced down-regulation of CXCR4 is not due to proteolytic degradation. The down-regulation of CXCR4 is mainly due to the inhibition of nuclear factor κB (NF-κB) transcriptional activity. Apigenin also abolished migration and invasion of transformed cells induced by CXCL12. In a xenograft mouse model, apigenin down-regulated CXCR4 expression and suppressed tumor growth. Taken together, our results show that apigenin is a novel inhibitor of CXCR4 expression. This dietary flavonoid has the potential to suppress migration and invasion of transformed cells and prevent environmental arsenic-induced carcinogenesis. - Highlights: • Apigenin has a potential in preventing environmental arsenic induced carcinogenesis. • Apigenin suppresses CXCR4 in malignant transformed cells in vitro and in vivo. • The down-regulation of CXCR4 is mainly due to inhibition of NF-κB activity.

  11. From Detailed Description of Chemical Reacting Carbon Particles to Subgrid Models for CFD

    Directory of Open Access Journals (Sweden)

    Schulze S.

    2013-04-01

    Full Text Available This work is devoted to the development and validation of a sub-model for the partial oxidation of a spherical char particle moving in an air/steam atmosphere. The particle diameter is 2 mm. The coal particle is represented by moisture- and ash-free nonporous carbon while the coal rank is implemented using semi-global reaction rate expressions taken from the literature. The submodel includes six gaseous chemical species (O2, CO2, CO, H2O, H2, N2. Three heterogeneous reactions are employed, along with two homogeneous semi-global reactions, namely carbon monoxide oxidation and the water-gas-shift reaction. The distinguishing feature of the subgrid model is that it takes into account the influence of homogeneous reactions on integral characteristics such as carbon combustion rates and particle temperature. The sub-model was validated by comparing its results with a comprehensive CFD-based model resolving the issues of bulk flow and boundary layer around the particle. In this model, the Navier-Stokes equations coupled with the energy and species conservation equations were used to solve the problem by means of the pseudo-steady state approach. At the surface of the particle, the balance of mass, energy and species concentration was applied including the effect of the Stefan flow and heat loss due to radiation at the surface of the particle. Good agreement was achieved between the sub-model and the CFD-based model. Additionally, the CFD-based model was verified against experimental data published in the literature (Makino et al. (2003 Combust. Flame 132, 743-753. Good agreement was achieved between numerically predicted and experimentally obtained data for input conditions corresponding to the kinetically controlled regime. The maximal discrepancy (10% between the experiments and the numerical results was observed in the diffusion-controlled regime. Finally, we discuss the influence of the Reynolds number, the ambient O2 mass fraction and the ambient

  12. Strong spectral dependence of light absorption by organic carbon particles formed by propane combustion

    Directory of Open Access Journals (Sweden)

    M. Schnaiter

    2006-01-01

    Full Text Available We have measured the extinction and absorption cross sections of carbon particles emitted by a propane diffusion flame both in an aerosol chamber and on size-segregated samples deposited on optical windows. The absorption cross section, the single scattering albedo, and the Ångström exponent show drastic dependencies both on the C/O ratio and on the particle size. This is interpretated as being due to the appearance of nucleation modes of smaller organic particles at higher C/O ratios, which were detected by SMPS measurements and partially by TEM analysis. The spectral range of the validity of the absorption power-law (Ångström exponent model is investigated by vacuum ultraviolet extinction measurements. These measurements give also indications for a preferentially aromatic nature of the OC component of the flame products.

  13. Heterogeneous reactions of gaseous methanesulfonic acid with calcium carbonate and kaolinite particles

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Heterogeneous reactions of gaseous methanesulfonic acid (MSA) with calcium carbonate (CaCO3) and kaolinite particles at room temperature were investigated using diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) and ion chromatography (IC).Methanesulfonate (MS-) was identified as the product in the condensed phase,in accordance with the product of the reaction of gaseous MSA with NaCl and sea salt particles.When the concentration of gaseous MSA was 1.34 × 10-13 molecules cm-3,the uptake coefficient was (1.21 ± 0.06) × 10-8 (1) for the reaction of gaseous MSA with CaCO3 and (4.10 ± 0.65) × 10 10 (1) for the reaction with kaolinite.Both uptake coefficients were significantly smaller than those of the reactions of gaseous MSA with NaCl and sea salt particles.

  14. Numerical modelling of the internal mixing by coagulation of black carbon particles in aircraft exhaust

    Energy Technology Data Exchange (ETDEWEB)

    Ohlsson, S.; Stroem, J. [Stockholm Univ. (Sweden). Dept. of Meteorology

    1997-12-31

    When exhaust gases from an aircraft engine mix with ambient air the humidity may reach water saturation and water droplets will form on the available cloud condensation nuclei (CCN). It is still not resolved if the CCN, on which the cloud droplets form, are mainly particles present in the ambient air or particles emitted by the aircraft. It the exhaust from a jet engine the particles are believed to consist mainly of black carbon (BC) and sulfate. The aim is to study, with the help of a numerical model, how a two-component aerosol (i.e. BC and sulfate) in an exhaust trail may be transformed in terms of hygroscopicity by coagulation mixing and how this may depend on the sulfur content in the fuel. (R.P.) 15 refs.

  15. Three-particle correlation from a Many-Body Perspective: Trions in a Carbon Nanotube

    Science.gov (United States)

    Deilmann, Thorsten; Drüppel, Matthias; Rohlfing, Michael

    2016-05-01

    Trion states of three correlated particles (e.g., two electrons and one hole) are essential to understand the optical spectra of doped or gated nanostructures, like carbon nanotubes or transition-metal dichalcogenides. We develop a theoretical many-body description for such correlated states using an ab initio approach. It can be regarded as an extension of the widely used G W method and Bethe-Salpeter equation, thus allowing for a direct comparison with excitons. We apply this method to a semiconducting (8,0) carbon nanotube, and find that the lowest optically active trions are redshifted by ˜130 meV compared to the excitons, confirming experimental findings for similar tubes. Moreover, our method provides detailed insights in the physical nature of trion states. In the prototypical carbon nanotube we find a variety of different excitations, discuss the spectra, energy compositions, and correlated wave functions.

  16. Comparing activated carbon of different particle sizes on enhancing methane generation in upflow anaerobic digester.

    Science.gov (United States)

    Xu, Suyun; He, Chuanqiu; Luo, Liwen; Lü, Fan; He, Pinjing; Cui, Lifeng

    2015-11-01

    Two sizes of conductive particles, i.e. 10-20 mesh granulated activated carbon (GAC) and 80-100 mesh powdered activated carbon (PAC) were added into lab-scale upflow anaerobic sludge blanket reactors, respectively, to testify their enhancement on the syntrophic metabolism of alcohols and volatile fatty acids (VFAs) in 95days operation. When OLR increased to more than 5.8gCOD/L/d, the differences between GAC/PAC supplemented reactors and the control reactor became more significant. The introduction of activated carbon could facilitate the enrichment of methanogens and accelerate the startup of methanogenesis, as indicated by enhanced methane yield and substrate degradation. High-throughput pyrosequencing analysis showed that syntrophic bacteria and Methanosarcina sp. with versatile metabolic capability increased in the tightly absorbed fraction on the PAC surface, leading to the promoted syntrophic associations. Thus PAC prevails over than GAC for methanogenic reactor with heavy load. PMID:26298405

  17. Preliminary study on preparation of BCNO phosphor particles using citric acid as carbon source

    Energy Technology Data Exchange (ETDEWEB)

    Nuryadin, Bebeh W.; Pratiwi, Tripuspita; Faryuni, Irfana D.; Iskandar, Ferry, E-mail: ferry@fi.itb.ac.id; Abdullah, Mikrajuddin; Khairurrijal [Department of Physics, Faculty of Mathematics and Natural Sciences, Institut Teknologi Bandung, Ganesha 10 Bandung, Indonesia 40132 (Indonesia); Ogi, Takashi; Okuyama, Kikuo [Department of Chemical Engineering, Graduate School of Engineering, Hiroshima University, 1-4-1 Kagamiyama, Higashi Hiroshima, Japan 739-8527 (Japan)

    2015-04-16

    A citric acid was used as a carbon source in the preparation of boron carbon oxy-nitride (BCNO) phosphor particles by a facile process. The preparation process was conducted at relatively low temperature 750 °C and at ambient pressure. The prepared BCNO phosphors showed a high photoluminescence (PL) performance at peak emission wavelength of 470 nm under excitation by a UV light 365 nm. The effects of carbon/boron and nitrogen/boron molar ratios on the PL properties were also investigated. The result showed that the emission spectra with a wavelength peak ranging from 444 nm to 496 nm can be obtained by varying carbon/boron ratios from 0.1 to 0.9. In addition, the observations showed that the BCNO phosphor material has two excitation peaks located at the 365 nm (UV) and 420 nm (blue). Based on these observations, we believe that the citric acid derived BCNO phosphor particles can be a promising inexpensive material for phosphor conversion-based white LED.

  18. Down-regulation of miR-302b, an ESC-specific microRNA, in Gastric Adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Seyed Javad Mowla

    2012-01-01

    -tumorgastric tissue samples. The data further revealed a down-regulation of miR-302b in gastrictumor samples (p=0.001, particularly in high-grade adenocarcinoma (p=0.009. However,ROC analysis data demonstrated a low sensitivity and specificity of miR-302b expressionto discriminate between the tumor and non-tumor state of the samples (AUC=0.63.Conclusion: Despite the upregulation of some hESC-specific genes in tumors, our datarevealed a down-regulation of miR-302b in high-grade tumors. This data suggested a potentialtumor-suppressor role for miR-302b in tumorigenesis of gastric tissue.

  19. Moxibustion down-regulates colonic epithelial cell apoptosis and repairs tight junctions in rats with Crohn's disease

    Institute of Scientific and Technical Information of China (English)

    Chun-Hui Bao; Lu-Yi Wu; Yin Shi; Huan-Gan Wu; Hui-Rong Liu; Rong Zhang; Li-Qing Yu; Jin-Hai Wang

    2011-01-01

    AIM: To investigate the effects of moxibustion on down-regulation of the colonic epithelial cell apoptosis and repair of the tight junctions in rats with Crohn's disease (CD).METHODS: Sixty male Sprague-Dawley rats were randomly divided into a normal control (NC) group, a model control (MC) group, an herbs-partitioned moxibustion (HPM) group, a mild-warm moxibustion (MWM) group and a salicylazosulphapyridine (SASP) group, with 12 rats in each group. The CD model rats were treated with trinitrobenzene sulphonic acid to induce intestinal inflammation. The rats in the HPM and MWM groups were treated at the Tianshu (ST25) and Qihai (CV6) acupoints once daily for 14 d, and the SASP group was fed SASP twice daily for 14 d. No additional treatment was given to the MC and NC groups. The microstructure of the colonic epithelium was observed under a transmission electron microscope, the transepithelial resistance was measured using a short-circuit current, colonic epithelial cell apoptosis was determined by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labelling assay, and the expression of occludin, claudin-1 and zonula occludens-l (ZO-1) in the colonic epithelial junction was determined by Western blotting and immunofluorescence staining.RESULTS: Compared with the MC group, the microstructure of the colonic epithelial barrier was significantly improved in rats treated with HPM, MWM or SASP, meanwhile, the current flow was reduced significantly, with values of 168.20 ± 6.14 vs 99.70 ± 3.13, 99.10 ± 4.28 and 120.30 ± 3.65 mA, respectively (P = 0.001). However, the HPM and MWM groups had higher current flow rates than the SASP group (99.70 ± 3.13, 99.10 ± 4.28 vs 120.30 ± 3.65 mA, P = 0.001). The number of the apoptotic colonic epithelial cells in HPM, MWM and SASP groups was largely reduced (61.5 ± 16.91 vs 15.5 ± 8.89, 14.8 ± 6.27 and 24.7 ± 9.68, respectively (P = 0.001); and the expression of occludin, claudin-1 and ZO-1 in the MWM and HPM

  20. NDRG2 Expression Decreases Tumor-Induced Osteoclast Differentiation by Down-regulating ICAM1 in Breast Cancer Cells.

    Science.gov (United States)

    Kim, Bomi; Nam, Sorim; Lim, Ji Hyun; Lim, Jong-Seok

    2016-01-01

    Bone matrix is properly maintained by osteoclasts and osteoblasts. In the tumor microenvironment, osteoclasts are increasingly differentiated by the various ligands and cytokines secreted from the metastasized cancer cells at the bone metastasis niche. The activated osteoclasts generate osteolytic lesions. For this reason, studies focusing on the differentiation of osteoclasts are important to reduce bone destruction by tumor metastasis. The N-myc downstream-regulated gene 2 (NDRG2) has been known to contribute to the suppression of tumor growth and metastasis, but the precise role of NDRG2 in osteoclast differentiation induced by cancer cells has not been elucidated. In this study, we demonstrate that NDRG2 expression in breast cancer cells has an inhibitory effect on osteoclast differentiation. RAW 264.7 cells, which are monocytic preosteoclast cells, treated with the conditioned media (CM) of murine breast cancer cells (4T1) expressing NDRG2 are less differentiated into the multinucleated osteoclast-like cells than those treated with the CM of 4T1-WT or 4T1-mock cells. Interestingly, 4T1 cells stably expressing NDRG2 showed a decreased mRNA and protein level of intercellular adhesion molecule 1 (ICAM1), which is known to enhance osteoclast maturation. Osteoclast differentiation was also reduced by ICAM1 knockdown in 4T1 cells. In addition, blocking the interaction between soluble ICAM1 and ICAM1 receptors significantly decreased osteoclastogenesis of RAW 264.7 cells in the tumor environment. Collectively, these results suggest that the reduction of ICAM1 expression by NDRG2 in breast cancer cells decreases osteoclast differentiation, and demonstrate that excessive bone resorption could be inhibited via ICAM1 down-regulation by NDRG2 expression.

  1. Metformin reduces the endotoxin-induced down-regulation of apolipoprotein E gene expression in macrophages

    Energy Technology Data Exchange (ETDEWEB)

    Stavri, Simona; Trusca, Violeta G.; Simionescu, Maya; Gafencu, Anca V., E-mail: anca.gafencu@icbp.ro

    2015-05-29

    The atheroprotective role of macrophage-derived apolipoprotein E (apoE) is well known. Our previous reports demonstrated that inflammatory stress down-regulates apoE expression in macrophages, aggravating atherogenesis. Metformin, extensively used as an anti-diabetic drug, has also anti-inflammatory properties, and thus confers vascular protection. In this study, we questioned whether metformin could have an effect on apoE expression in macrophages in normal conditions or under lipopolysaccharide (LPS)-induced stress. The results showed that metformin slightly increases the apoE expression only at high doses (5–10 mM). Low doses of metformin (1–3 mM) significantly reduce the LPS down-regulatory effect on apoE expression in macrophages. Our experiments demonstrated that LPS-induced NF-κB binds to the macrophage-specific distal regulatory element of apoE gene, namely to the multienhancer 2 (ME.2) and its 5′-deletion fragments. The NF-κB binding on ME.2 and apoE promoter has a down-regulatory effect. In addition, data revealed that metformin impairs NF-κB nuclear translocation, and thus, improves the apoE levels in macrophages under inflammatory stress. The positive effect of metformin in the inflammatory states, its clinical safety and low cost, make this drug a potential adjuvant in the therapeutic strategies for atherosclerosis. - Highlights: • High doses of metformin slightly increase apoE expression in macrophages. • Low doses of metformin up-regulate apoE gene in endotoxin-stressed macrophages. • Metformin reduces the negative effect of LPS on apoE expression by NF-κB inhibition.

  2. Melittin induces PTCH1 expression by down-regulating MeCP2 in human hepatocellular carcinoma SMMC-7721 cells.

    Science.gov (United States)

    Wu, Xiaoqin; Zhao, Bin; Cheng, Yahui; Yang, Yang; Huang, Cheng; Meng, Xiaoming; Wu, Baoming; Zhang, Lei; Lv, Xiongwen; Li, Jun

    2015-10-01

    Hepatocellular carcinoma (HCC) has a high mortality rate worldwide and still remains to be a noticeable public health problem. Therefore, new remedies are urgently needed. Melittin, a major component of bee venom, is known to suppress cell growth in various cancers including HCC. However, the mechanism of the anticancer effect of melittin on HCC has not been fully elucidated. It has been reported that Methyl-CpG binding protein 2 (MeCP2) plays a key role in tumor proliferation, apoptosis, migration and invasion. In the present study, we found the high expression of MeCP2 in human HCC tissues and in the SMMC-7721 cell line. MeCP2 silencing inhibited cell proliferation, while over-expression of MeCP2 promoted cell growth in SMMC-7721 cells. It indicates that MeCP2 may be an attractive target for human HCC. We further found that melittin could inhibit cell proliferation by reducing MeCP2 expression in vitro. Interestingly, the inhibitory effect of melittin on cell proliferation was due to a delay in G0/G1 cell cycle progression, without influencing cell apoptosis. Next, we investigated the potential molecular mechanisms and found that MeCP2 could modulate Shh signaling in SMMC-7721 cells. Further study indicates that melittin may induce the demethylation of PTCH1 promoter, resulting in the increased expression of PTCH1. Furthermore, the expression of Shh and GLI1 was significantly lowered upon treatment of melittin. These results suggest that melittin can block Shh signaling in vitro. In short, these results indicate that melittin inhibits cell proliferation by down-regulating MeCP2 through Shh signaling in SMMC-7721 cells. PMID:26189965

  3. Intestinal commensal bacteria promote T cell hyporesponsiveness and down-regulate the serum antibody responses induced by dietary antigen.

    Science.gov (United States)

    Tsuda, Masato; Hosono, Akira; Yanagibashi, Tsutomu; Kihara-Fujioka, Miran; Hachimura, Satoshi; Itoh, Kikuji; Hirayama, Kazuhiro; Takahashi, Kyoko; Kaminogawa, Shuichi

    2010-08-16

    Colonization of the gut by commensal bacteria modulates the induction of oral tolerance and allergy. However, how these intestinal bacteria modulate antigen-specific T cell responses induced by oral antigens remains unclear. In order to investigate this, we used germ-free (GF) ovalbumin (OVA)-specific T cell receptor transgenic (OVA23-3) mice. Conventional (CV) or GF mice were administered an OVA-containing diet. Cytokine production by CD4(+) cells from spleen (SP), mesenteric lymph nodes (MLN) and Peyer's patches (PP) was evaluated by ELISA, as was the peripheral antibody titer. T cell phenotype was assessed by flow cytometry. CD4(+) cells from the SP and MLN of CV and GF mice fed an OVA diet for 3 weeks produced significantly less IL-2 than the corresponding cells from mice receiving a control diet, suggesting that oral tolerance could be induced at the T cell level in the systemic and intestinal immune systems of both bacterial condition of mice. However, we also observed that the T cell hyporesponsiveness induced by dietary antigen was delayed in the systemic immune tissues and was weaker in the intestinal immune tissues of the GF mice. Intestinal MLN and PP CD4(+) T cells from these animals also produced lower levels of IL-10, had less activated/memory type CD45RB(low) cells, and expressed lower levels of CTLA-4 but not Foxp3 compared to their CV counterparts. Furthermore, GF mice produced higher serum levels of OVA-specific antibodies than CV animals. CD40L expression by SP CD4(+) cells from GF mice fed OVA was higher than that of CV mice. These results suggest that intestinal commensal bacteria promote T cell hyporesponsiveness and down-regulate serum antibody responses induced by dietary antigens through modulation of the intestinal and systemic T cell phenotype. PMID:20621647

  4. Zeranol Down-Regulates p53 Expression in Primary Cultured Human Breast Cancer Epithelial Cells through Epigenetic Modification

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    Young C. Lin

    2011-02-01

    Full Text Available Epidemiological studies have suggested that there are many risk factors associated with breast cancer. Silencing tumor suppressor genes through epigenetic alterations play critical roles in breast cancer initiation, promotion and progression. As a growth promoter, Zeranol (Z has been approved by the FDA and is widely used to enhance the growth of beef cattle in the United States. However, the safety of Z use as a growth promoter is still under debate. In order to provide more evidence to clarify this critical health issue, the current study investigated the effect of Z on the proliferation of primary cultured human normal and cancerous breast epithelial cells (PCHNBECs and PCHBCECs, respectively isolated from the same patient using MTS assay, RT-PCR and Western blot analysis. We also conducted an investigation regarding the mechanisms that might be involved. Our results show that Z is more potent to stimulate PCHBCEC growth than PCHNBEC growth. The stimulatory effects of Z on PCHBCECs and PCHBCECs may be mediated by its down-regulating expression of the tumor suppressor gene p53 at the mRNA and protein levels. Further investigation showed that the expression of DNA methylatransferase 1 mRNA and protein levels is up-regulated by treatment with Z in PCHBCECs as compared to PCHNBECs, which suggests a role of Z in epigenetic modification involved in the regulation of p53 gene expression in PCHBCECs. Our experimental results imply the potentially adverse health effect of Z in breast cancer development. Further study is continuing in our laboratory.

  5. Down-regulated expression of atypical PKC-binding domain deleted asip isoforms in human hepatocellular carcinomas

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Asip is a mammalian homologue of polarity protein Par-3 of Caenorhabditis elegans and Bazooka of Drosophila melanogaster. Asip/Par-3/Bazooka are PDZ-motif containing proteins that localize asymmetrically to the cell periphery and play a pivotal role in cell polarity and asymmetric cell division. In the present study, we have cloned human asip cDNA and its splicing variants by 5'-RACE and RT-PCR using candidate human EST clones which have a high homology to rat asip cDNA. The full-length cDNA of human asip encodes a 1,353 aa protein exhibiting 88% similarity to the rat one. Human asip is a single copy gene consisting of at least 26 exons and localizing in human chromosome 10, band p11.2, with some extraordinarily long introns. All exon/intron boundary nucleotides conform to the “gt-ag” rule. Three main transcripts were detected by Northern blot analysis, and at least five variants, from alternative splicing and polyadenylation, have been identified by RT-PCR and liver cDNA library screening. Exon 17b deleted asip mRNAs expressed ubiquitously in normal human tissues, including liver, on RT-PCR analysis. However, they were absent from most human liver cancer cell lines examined. More interestingly, the expression of exon 17b deleted variants was down regulated in 52.6% (10/19) clinic specimens of human hepatocellular carcinomas (HCCs), compared with the surrounding nontumorous liver tissues from the same patients. The presence of various splicing transcripts, the variation of their distribution among different tissues and cells, and their differential expressions in human HCCs suggest that human Asip isoforms may function in different context.

  6. Down-regulation of POLYGALACTURONASE1 alters firmness, tensile strength and water loss in apple (Malus x domestica fruit

    Directory of Open Access Journals (Sweden)

    Atkinson Ross G

    2012-08-01

    Full Text Available Abstract Background While there is now a significant body of research correlating apple (Malus x domestica fruit softening with the cell wall hydrolase ENDO-POLYGALACTURONASE1 (PG1, there is currently little knowledge of its physiological effects in planta. This study examined the effect of down regulation of PG1 expression in ‘Royal Gala’ apples, a cultivar that typically has high levels of PG1, and softens during fruit ripening. Results PG1-suppressed ‘Royal Gala’ apples harvested from multiple seasons were firmer than controls after ripening, and intercellular adhesion was higher. Cell wall analyses indicated changes in yield and composition of pectin, and a higher molecular weight distribution of CDTA-soluble pectin. Structural analyses revealed more ruptured cells and free juice in pulled apart sections, suggesting improved integrity of intercellular connections and consequent cell rupture due to failure of the primary cell walls under stress. PG1-suppressed lines also had reduced expansion of cells in the hypodermis of ripe apples, resulting in more densely packed cells in this layer. This change in morphology appears to be linked with reduced transpirational water loss in the fruit. Conclusions These findings confirm PG1’s role in apple fruit softening and suggests that this is achieved in part by reducing cellular adhesion. This is consistent with previous studies carried out in strawberry but not with those performed in tomato. In apple PG1 also appears to influence other fruit texture characters such as juiciness and water loss.

  7. Down-regulation of gut-enriched Krüppel-like factor expression in esophageal cancer

    Institute of Scientific and Technical Information of China (English)

    Nan Wang; Zhi-Hua Liu; Fang Ding; Xiu-Qin Wang; Chuan-Nong Zhou; Min Wu

    2002-01-01

    AIM: Esophageal carcinoma is one of the most common malignant tumors in China. But the molecular mechanisms of esophageal carcinoma remains unclear. Gut-enriched factor which is expressed abandantly in the epithelial cells of the gastrointestinal tract and deregulation of GKLF was linked to several types of cancer. It is of interest to study the expression and role of GKLF in esophageal carcinoma.METHODS: Semi-quantitative RT-PCR was used to compare GKLF expression in esophageal squamous cell carcinoma to normal mucosa of the same patients. The serum deprivation inducibility of GKLF was observed in an esophageal squamous cancer cell line by comparison to the primary culture of human fibroblast. The effect of antisense GKLF transfection on the proliferation and adhesion of esophageal squamous cancer cell line was also observed.RESULTS: The level of GKLF transcript is lower in esophageal squamous cell carcinoma compared to paired normal-appearing mucosa in 14 of 17 of the tumors analyzed.The serum deprivation inducibility of GKLF was greatly decreased in an esophageal squamous cancer cell line compared to the primary culture of human fibroblast.Decreased expression of GKLF in the esophageal cancer cell by antisense GKLF transfection increased its proliferation rate compared with that of vector transfected cell control (P<0.05). Transfection of antisense GKLF decreased its adhesion ability (P<0.05).CONCLUSION: The findings of this study demonstrate the down-regulation of GKLF in esophageal squamous cancer,and suggest that deregulation of GKLF may play a role in initiation and/or progression as well as the metastasis of esophageal squamous cancer.

  8. JNK phosphorylation promotes degeneration of cervical endplate chondrocytes through down-regulation of the expression of ANK in humans

    Institute of Scientific and Technical Information of China (English)

    XU Hong-guang; SONG Jun-xing; CHENG Jia-feng; ZHANG Ping-Zhi; WANG Hong; LIU Ping; L(U) Kun

    2013-01-01

    Background C-Jun N-terminal kinase (JNK) signaling pathway and ankylosis gene (ANK) play a critical role in endplate chondrocytes degeneration.The purpose of this study was to investigate whether the expression levels of ANK was associated with the activation of JNK.Methods Cartilage endplates of 49 patients were divided into the control group (n=19) and the experimental group (n=30).The patients in the control group were graded 0 and those in the experimental group were graded Ⅰ-Ⅲ according to Miller's classification.Endplate chondrocytes were isolated by enzyme digestion and cultured in vitro.The inverted phase contrast microscope,teluidine blue staining,HE staining,real time RT-PCR,and MTT were used to observe morphological appearances,biological characteristics,and growth curve of endplate chondrocytes from the cartilage endplate of the two groups.Real time RT-PCR and Western blotting were used to analyze the mRNA and protein expression levels of associated factors in the degeneration process in the cultured endplate chondrocytes with or without subjected SP600125.Results The expression levels of type Ⅱ collagen,aggrecan,and ANK in endplate chondrocytes of experimental group were lower than that of control group and phosphorylation level of JNK in the experimental group which was higher than that in the control group.Application of JNK phosphorylation inhibitor to degeneration chondrocytes resulted in a marked decrease in the phosphorylation level of JNK and a significant increase in the expression levels of type Ⅱ collagen,aggrecan,and ANK.Conclusion The degeneration of the human cervical endplate chondrocytes might be promoted by JNK phosphorylation by down-regulating the expression of ANK

  9. Low Light Stress Down-Regulated Rubisco Gene Expression and Photosynthetic Capacity During Cucumber (Cucumis sativus L.) Leaf Development

    Institute of Scientific and Technical Information of China (English)

    SUN Jian-lei; SUI Xiao-lei; HUANG Hong-yu; WANG Shao-hui; WEI Yu-xia; ZHANG Zhen-xian

    2014-01-01

    Low light stress is one of the most important factors affecting photosynthesis and growth in winter production of cucumber (Cucumis sativus L.) in solar greenhouses in northern China. Here, two genotypes of cucumber (Deltastar and Jinyan 2) are used to determine the effect of low light stress on Rubisco expression and photosynthesis of leaves from emergence to senescence. During leaf development, the net photosynthetic rate (PN), stomatal conductance (gs), Rubisco initial activity and activation state, transcript levels of rbcL and rbcS, and the abundance of rbcL and rbcS DNA in these two genotypes increase rapidly to reach maximum in 10-20 d, and then decrease gradually. Meanwhile, the actual photosystem II efifciency (ФPSI ) of cucumber leaves slowly increased in the early leaf developing stages, but it declined quickly in leaf senescent stages, accompanied by an increased non-photochemical quenching (NPQ). Moreover, PN, gs, initial Rubisco activity, and abundance of protein, mRNA and DNA of Rubisco subunits of leaves grown under 100μmol m-2 s-1 are lower, and require more time to reach their maxima than those grown under 600μmol m-2 s-1 during leaf development. All these results suggest that lower photosynthetic capacity of cucumber leaves from emergence to senescence under low light stress is probably due to down-regulated Rubisco gene expression in transcript and protein levels, and decreased initial and total activity as well as activation state of Rubisco. Deltastar performs better than Jinyan 2 under low light stress.

  10. Limb immobilization induces a coordinate down-regulation of mitochondrial and other metabolic pathways in men and women.

    Directory of Open Access Journals (Sweden)

    Arkan Abadi

    Full Text Available Advancements in animal models and cell culture techniques have been invaluable in the elucidation of the molecular mechanisms that regulate muscle atrophy. However, few studies have examined muscle atrophy in humans using modern experimental techniques. The purpose of this study was to examine changes in global gene transcription during immobilization-induced muscle atrophy in humans and then explore the effects of the most prominent transcriptional alterations on protein expression and function. Healthy men and women (N = 24 were subjected to two weeks of unilateral limb immobilization, with muscle biopsies obtained before, after 48 hours (48 H and 14 days (14 D of immobilization. Muscle cross sectional area (approximately 5% and strength (10-20% were significantly reduced in men and women (approximately 5% and 10-20%, respectively after 14 D of immobilization. Micro-array analyses of total RNA extracted from biopsy samples at 48 H and 14 D uncovered 575 and 3,128 probes, respectively, which were significantly altered during immobilization. As a group, genes involved in mitochondrial bioenergetics and carbohydrate metabolism were predominant features at both 48 H and 14 D, with genes involved in protein synthesis and degradation significantly down-regulated and up-regulated, respectively, at 14 D of muscle atrophy. There was also a significant decrease in the protein content of mitochondrial cytochrome c oxidase, and the enzyme activity of cytochrome c oxidase and citrate synthase after 14 D of immobilization. Furthermore, protein ubiquitination was significantly increased at 48 H but not 14 D of immobilization. These results suggest that transcriptional and post-transcriptional suppression of mitochondrial processes is sustained throughout 14 D of immobilization, while protein ubiquitination plays an early but transient role in muscle atrophy following short-term immobilization in humans.

  11. Nutrient/serum starvation derived TRIP-Br3 down-regulation accelerates apoptosis by destabilizing XIAP

    Science.gov (United States)

    Lee, Soonduck; Jeong, Dongjun; Yang, Young; Kim, Keun-Il; Lim, Jong-Seok; Cheon, Chung-Il; Kim, Changjin; Kang, Young-Sook; Lee, Myeong-Sok

    2015-01-01

    TRIP-Br3 and TRIP-Br1 have shown to have important biological functions. However, the function of TRIP-Br3 in tumorigenesis is not well characterized compared to oncogenic TRIP-Br1. Here, we investigated the function of TRIP-Br3 in tumorigenesis by comparing with that of TRIP-Br1. Under nutrient/serum starvation, TRIP-Br3 expression was down-regulated slightly in cancer cells and significantly in normal cells. Unexpectedly, TRIP-Br1 expression was greatly up-regulated in cancer cells but not in normal cells. Moreover, TRIP-Br3 activated autophagy while TRIP-Br1 inactivated it under serum starvation. In spite of different expression and roles of TRIP-Br3 and TRIP-Br1, both of them alleviate cell death by directly binding to and stabilizing XIAP, a potent apoptosis inhibitor, through blocking its ubiquitination. Taken together, we propose that TRIP-Br3 primarily activates the autophagy and suppresses apoptosis in nutrient sufficient condition. However, the prolonged extreme stressful condition of nutrient starvation causes a dramatic decrease of TRIP-Br3, which in turn induces apoptosis by destabilizing XIAP. Up-regulated TRIP-Br1 in cancer cells compensates this effect and delays apoptosis. This can be explained by the competitive alternative binding of TRIP-Br3 and TRIP-Br1 to the BIR2 domain of XIAP. In an extended study, our immunohistochemical analysis revealed a markedly lower level of TRIP-Br3 protein in human carcinoma tissues compared to normal epithelial tissues, implying the role of TRIP-Br3 as a tumor suppressor rather than onco-protein. PMID:25691055

  12. Foxa1 reduces lipid accumulation in human hepatocytes and is down-regulated in nonalcoholic fatty liver.

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    Marta Moya

    Full Text Available Triglyceride accumulation in nonalcoholic fatty liver (NAFL results from unbalanced lipid metabolism which, in the liver, is controlled by several transcription factors. The Foxa subfamily of winged helix/forkhead box (Fox transcription factors comprises three members which play important roles in controlling both metabolism and homeostasis through the regulation of multiple target genes in the liver, pancreas and adipose tissue. In the mouse liver, Foxa2 is repressed by insulin and mediates fasting responses. Unlike Foxa2 however, the role of Foxa1 in the liver has not yet been investigated in detail. In this study, we evaluate the role of Foxa1 in two human liver cell models, primary cultured hepatocytes and HepG2 cells, by adenoviral infection. Moreover, human and rat livers were analyzed to determine Foxa1 regulation in NAFL. Results demonstrate that Foxa1 is a potent inhibitor of hepatic triglyceride synthesis, accumulation and secretion by repressing the expression of multiple target genes of these pathways (e.g., GPAM, DGAT2, MTP, APOB. Moreover, Foxa1 represses the fatty acid transporter protein FATP2 and lowers fatty acid uptake. Foxa1 also increases the breakdown of fatty acids by inducing peroxisomal fatty acid β-oxidation and ketone body synthesis. Finally, Foxa1 is able to largely up-regulate UCP1, thereby dissipating energy and consistently decreasing the mitochondria membrane potential. We also report that human and rat NAFL have a reduced Foxa1 expression, possibly through a protein kinase C-dependent pathway. We conclude that Foxa1 is an antisteatotic factor that coordinately tunes several lipid metabolic pathways to block triglyceride accumulation in hepatocytes. However, Foxa1 is down-regulated in human and rat NAFL and, therefore, increasing Foxa1 levels could protect from steatosis. Altogether, we suggest that Foxa1 could be a novel therapeutic target for NAFL disease and insulin resistance.

  13. Arthrophytum scoparium inhibits melanogenesis through the down-regulation of tyrosinase and melanogenic gene expressions in B16 melanoma cells.

    Science.gov (United States)

    Chao, Hui-Chia; Najjaa, Hanen; Villareal, Myra O; Ksouri, Riadh; Han, Junkyu; Neffati, Mohamed; Isoda, Hiroko

    2013-02-01

    Melanin performs a crucial role in protecting the skin against harmful ultraviolet light. However, hyperpigmentation may lead to aesthetic problems and disorders such as solar lentigines (SL), melasma, postinflammatory hyperpigmentation and even melanoma. Arthrophytum scoparium grows in the desert in the North African region, and given this type of environment, A. scoparium exhibits adaptations for storing water and produces useful bioactive factors. In this study, the effect of A. scoparium ethanol extract (ASEE) on melanogenesis regulation in B16 murine melanoma cells was investigated. Cells treated with 0.017% (w/v) ASEE showed a significant inhibition of melanin biosynthesis in a time-dependent manner without cytotoxicity. To clarify the mechanism behind the ASEE-treated melanogenesis regulation, the expressions of tyrosinase enzyme and melanogenesis-related genes were determined. Results showed that the expression of tyrosinase enzyme was significantly decreased and Tyr, Trp-1, Mitf and Mc1R mRNA expressions were significantly down-regulated. LC-ESI-TOF-MS analysis of the extract identified the presence of six phenolic compounds: coumaric acid, cinnamic acid, chrysoeriol, cyanidin, catechol and caffeoylquinic acid. The melanogenesis inhibitory effect of ASEE may therefore be attributed to its catechol and tetrahydroisoquinoline derivative content. We report here that ASEE can inhibit melanogenesis in a time-dependent manner by decreasing the tyrosinase protein and Tyr, Trp-1, Mitf and Mc1R mRNA expressions. This is the first report on the antimelanogenesis effect of A. scoparium and on its potential as a whitening agent. PMID:23362872

  14. siRNA against presenilin 1 (PS1 down regulates amyloid β42 production in IMR-32 cells

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    Kandimalla Ramesh JL

    2012-01-01

    Full Text Available Abstract Background One of the pathological hallmarks of Alzheimer's disease (AD is the deposition of the ~4 kDa amyloid β protein (Aβ within lesions known as senile plaques. Aβ is also deposited in the walls of cerebral blood vessels in many cases of AD. A substantial proportion of the Aβ that accumulates in the AD brain is deposited as Amyloid, which is highly insoluble, proteinaceous material with a β-pleated-sheet conformation and deposited extracellularly in the form of 5-10 nm wide straight fibrils. As γ-secretase catalyzes the final cleavage that releases the Aβ42 or 40 from amyloid β -protein precursor (APP, therefore, it is a potential therapeutic target for the treatment of AD. γ-Secretase cleavage is performed by a high molecular weight protein complex containing presenilins (PSs, nicastrin, Aph-1 and Pen-2. Previous studies have demonstrated that the presenilins (PS1 and PS2 are critical components of a large enzyme complex that performs γ-secretase cleavage. Methods In this study we used RNA interference (RNAi technology to examine the effects of small-interfering RNA (siRNA against PS1 on expression levels of PS1 and Aβ42 in IMR-32 Cells using RTPCR, western blotting and immunofluorescence techniques. Results The results of the present study showed down regulation of PS1 and Aβ42 in IMR32 cells transfected with siRNA against PS1. Conclusion Our results substantiate the concept that PS1 is involved in γ-secretase activity and provides the rationale for therapeutic strategies aimed at influencing Aβ42 production.

  15. Cetuximab in combination with anti-human IgG antibodies efficiently down-regulates the EGF receptor by macropinocytosis

    Energy Technology Data Exchange (ETDEWEB)

    Berger, Christian [Department of Pathology, Oslo University Hospital, Rikshospitalet, Post box 4950 Nydalen, 0424 Oslo (Norway); Madshus, Inger Helene [Institute of Pathology, University of Oslo, Rikshospitalet, 0027 Oslo (Norway); Department of Pathology, Oslo University Hospital, Rikshospitalet, Post box 4950 Nydalen, 0424 Oslo (Norway); Stang, Espen, E-mail: espsta@rr-research.no [Department of Pathology, Oslo University Hospital, Rikshospitalet, Post box 4950 Nydalen, 0424 Oslo (Norway)

    2012-12-10

    The monoclonal antibody C225 (Cetuximab) blocks binding of ligand to the epidermal growth factor receptor (EGFR). In addition, it is known that incubation with C225 induces endocytosis of the EGFR. This endocytosis has previously been shown to be increased when C225 is combined with an additional monoclonal anti-EGFR antibody. However, the effects of antibody combinations on EGFR activation, endocytosis, trafficking and degradation have been unclear. By binding a secondary antibody to the C225-EGFR complex, we here demonstrate that a combination of antibodies can efficiently internalize and degrade the EGFR. Although the combination of antibodies activated the EGFR kinase and induced ubiquitination of the EGFR, the kinase activity was not required for internalization of the EGFR. In contrast to EGF-induced EGFR down-regulation, the antibody combination efficiently degraded the EGFR without initiating downstream proliferative signaling. The antibody-induced internalization of EGFR was found not to depend on clathrin and/or dynamin, but depended on actin polymerization, suggesting induction of macropinocytosis. Macropinocytosis may cause internalization of large membrane areas, and this could explain the highly efficient internalization of the EGFR induced by combination of antibodies. -- Highlight: Black-Right-Pointing-Pointer Cetuximab induced endocytosis of EGFR increases upon combination with anti-human IgG. Black-Right-Pointing-Pointer Antibody combination causes internalization of EGFR by macropinocytosis. Black-Right-Pointing-Pointer Antibody-induced internalization of EGFR is independent of EGFR kinase activity. Black-Right-Pointing-Pointer Antibody combination may have a zipper effect and cross-link EGFRs on neighboring cells.

  16. Cadmium exposure down-regulates 8-oxoguanine DNA glycosylase expression in rat lung and alveolar epithelial cells

    International Nuclear Information System (INIS)

    The current study tested the hypothesis that the pulmonary carcinogenic potential of cadmium (Cd) is related to its ability to inhibit the expression (mRNA and protein) and activity of 8-oxoguanine-DNA glycosylase (OGG1), a base excision repair (BER) enzyme that functions to preferentially excise pre-mutagenic 7,8-dihydro-8-oxoguanine (8-oxoG) from DNA. We demonstrate that a single Cd aerosol exposure of adult male Lewis rats causes time- and dose-dependent down-regulation in the pulmonary levels of rOGG1 mRNA and OGG1 protein, quantified by real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assays and western analyses, respectively. Immunohistochemical studies confirmed that Cd inhalation reduces the relative amount of OGG1 in lungs of exposed animals without altering its over-all distribution within the lung, which appears to be more prominent within the alveolar epithelium. In agreement with our in vivo studies, we show that OGG1 expression is also attenuated in alveolar epithelial cell cultures exposed to CdCl2 either acutely or by repeated passaging in Cd-containing medium. The effects caused by Cd were observed in cells that show no loss in viability, as assessed by colony forming ability, the MTT assay, and propidium iodide membrane permeability studies. Nuclear extracts prepared from Cd-treated cells also exhibit a reduction in the ability to nick a synthetic oligonucleotide containing 8-oxoG. We conclude from these studies that Cd causes suppression of OGG1 in the lung and that this mechanism may, in part, play a role in the Cd carcinogenic process

  17. Methyl jasmonate abolishes the migration, invasion and angiogenesis of gastric cancer cells through down-regulation of matrix metalloproteinase 14

    International Nuclear Information System (INIS)

    Recent evidence indicates that methyl jasmonate (MJ), a plant stress hormone, exhibits anti-cancer activity on human cancer cells. The aim of this study is to determine whether sub-cytotoxic MJ can abolish the migration, invasion and angiogenesis gastric cancer cells. Human gastric cancer cell lines SGC-7901 and MKN-45 were treated with diverse concentrations of MJ. Cell viability, proliferation, migration, invasion and angiogenesis capabilities of cancer cells were measured by MTT colorimetry, EdU incorporation, scratch assay, matrigel invasion assay, and tube formation assay. Gene expression was detected by western blot and real-time quantitative RT-PCR. Binding of transcription factor on gene promoter was detected by chromatin immunoprecipitation. Sub-cytotoxic (0.05 to 0.2 mM) MJ attenuated the migration, invasion and angiogenesis, but not the cell viability or proliferation, of gastric cancer cells in a time- and dose-dependent manner, with down-regulation of matrix metalloproteinase 14 (MMP-14) and its downstream gene vascular endothelial growth factor. Restoration of MMP-14 expression rescued the SGC-7901 and MKN-45 cells from sub-cytotoxic MJ-inhibited migration, invasion and angiogenesis. In addition, sub-cytotoxic MJ decreased the specificity protein 1 (Sp1) expression and binding on MMP-14 promoter, while restoration of Sp1 expression rescued the cancer cells from sub-cytotoxic MJ-mediated defects in MMP-14 expression, migration, invasion and angiogenesis. Sub-cytotoxic MJ attenuates the MMP-14 expression via decreasing the Sp1 expression and binding on MMP-14 promoter, thus inhibiting the migration, invasion and angiogenesis of gastric cancer cells

  18. Down-regulation of PAR1 activity with a pHLIP-based allosteric antagonist induces cancer cell death.

    Science.gov (United States)

    Burns, Kelly E; Thévenin, Damien

    2015-12-15

    Even though abnormal expression of G protein-coupled receptors (GPCRs) and of their ligands is observed in many cancer cells of various origins, only a few anti-cancer compounds directly act on their signalling. One promising approach to modulate their activity consists of targeting the receptor cytoplasmic surfaces interacting with the associated G-proteins using peptides mimicking the intracellular loops of the receptor. Thus, to be fully effective, the peptide mimics must be selectively targeted to the tumour while sparing healthy tissues, translocated across the cell membrane and stay anchored to the cytoplasmic leaflet of the plasma membrane. In the present study, we introduce a novel way to selectively target and inhibit the activity of a GPCR in cancer cells under acidic conditions, such as those found in solid tumours. We find that the conjugation of a peptide fragment derived from the third intracellular loop (i3) of the protease-activated receptor 1 (PAR1) to a peptide that can selectively target tumours solely based on their acidity [pH(Low) Insertion Peptide (pHLIP)], produces a construct capable of effectively down-regulating PAR1 activity in a concentration- and pH-dependent manner and of inducing a potent cytotoxic effect in a panel of cancer cells that is proportional to the relative level of receptor expression at the cell surface. This strategy not only allows for a more selective targeting and specific intracellular delivery than current approaches, but also offers new possibilities for developing novel anti-cancer drugs targeting GPCRs. PMID:26424552

  19. Cetuximab in combination with anti-human IgG antibodies efficiently down-regulates the EGF receptor by macropinocytosis

    International Nuclear Information System (INIS)

    The monoclonal antibody C225 (Cetuximab) blocks binding of ligand to the epidermal growth factor receptor (EGFR). In addition, it is known that incubation with C225 induces endocytosis of the EGFR. This endocytosis has previously been shown to be increased when C225 is combined with an additional monoclonal anti-EGFR antibody. However, the effects of antibody combinations on EGFR activation, endocytosis, trafficking and degradation have been unclear. By binding a secondary antibody to the C225-EGFR complex, we here demonstrate that a combination of antibodies can efficiently internalize and degrade the EGFR. Although the combination of antibodies activated the EGFR kinase and induced ubiquitination of the EGFR, the kinase activity was not required for internalization of the EGFR. In contrast to EGF-induced EGFR down-regulation, the antibody combination efficiently degraded the EGFR without initiating downstream proliferative signaling. The antibody-induced internalization of EGFR was found not to depend on clathrin and/or dynamin, but depended on actin polymerization, suggesting induction of macropinocytosis. Macropinocytosis may cause internalization of large membrane areas, and this could explain the highly efficient internalization of the EGFR induced by combination of antibodies. -- Highlight: ► Cetuximab induced endocytosis of EGFR increases upon combination with anti-human IgG. ► Antibody combination causes internalization of EGFR by macropinocytosis. ► Antibody-induced internalization of EGFR is independent of EGFR kinase activity. ► Antibody combination may have a zipper effect and cross-link EGFRs on neighboring cells.

  20. Melatonin down-regulates MDM2 gene expression and enhances p53 acetylation in MCF-7 cells.

    Science.gov (United States)

    Proietti, Sara; Cucina, Alessandra; Dobrowolny, Gabriella; D'Anselmi, Fabrizio; Dinicola, Simona; Masiello, Maria Grazia; Pasqualato, Alessia; Palombo, Alessandro; Morini, Veronica; Reiter, Russel J; Bizzarri, Mariano

    2014-08-01

    Compelling evidence demonstrated that melatonin increases p53 activity in cancer cells. p53 undergoes acetylation to be stabilized and activated for driving cells destined for apoptosis/growth inhibition. Over-expression of p300 induces p53 acetylation, leading to cell growth arrest by increasing p21 expression. In turn, p53 activation is mainly regulated in the nucleus by MDM2. MDM2 also acts as E3 ubiquitin ligase, promoting the proteasome-dependent p53 degradation. MDM2 entry into the nucleus is finely tuned by two different modulations: the ribosomal protein L11, acts by sequestering MDM2 in the cytosol, whereas the PI3K-AkT-dependent MDM2 phosphorylation is mandatory for MDM2 translocation across the nuclear membrane. In addition, MDM2-dependent targeting of p53 is regulated in a nonlinear fashion by MDM2/MDMX interplay. Melatonin induces both cell growth inhibition and apoptosis in MCF7 breast cancer cells. We previously reported that this effect is associated with reduced MDM2 levels and increased p53 activity. Herein, we demonstrated that melatonin drastically down-regulates MDM2 gene expression and inhibits MDM2 shuttling into the nucleus, given that melatonin increases L11 and inhibits Akt-PI3K-dependent MDM2 phosphorylation. Melatonin induces a 3-fold increase in both MDMX and p300 levels, decreasing simultaneously Sirt1, a specific inhibitor of p300 activity. Consequently, melatonin-treated cells display significantly higher values of both p53 and acetylated p53. Thus, a 15-fold increase in p21 levels was observed in melatonin-treated cancer cells. Our results provide evidence that melatonin enhances p53 acetylation by modulating the MDM2/MDMX/p300 pathway, disclosing new insights for understanding its anticancer effect. PMID:24920214

  1. Apigenin ameliorates hypertension-induced cardiac hypertrophy and down-regulates cardiac hypoxia inducible factor-lα in rats.

    Science.gov (United States)

    Zhu, Zeng-Yan; Gao, Tian; Huang, Yan; Xue, Jie; Xie, Mei-Lin

    2016-04-20

    Apigenin is a natural flavonoid compound that can inhibit hypoxia-inducible factor (HIF)-1α expression in cultured tumor cells under hypoxic conditions. Hypertension-induced cardiac hypertrophy is always accompanied by abnormal myocardial glucolipid metabolism due to an increase of HIF-1α. However, whether or not apigenin may ameliorate the cardiac hypertrophy and abnormal myocardial glucolipid metabolism remains unknown. This study aimed to examine the effects of apigenin. Rats with cardiac hypertrophy induced by renovascular hypertension were treated with apigenin 50-100 mg kg(-1) (the doses can be achieved by pharmacological or dietary supplementation for an adult person) by gavage for 4 weeks. The results showed that after treatment with apigenin, the blood pressure, heart weight, heart weight index, cardiomyocyte cross-sectional area, serum angiotensin II, and serum and myocardial free fatty acids were reduced. It is important to note that apigenin decreased the expression level of myocardial HIF-1α protein. Moreover, apigenin simultaneously increased the expression levels of myocardial peroxisome proliferator-activated receptor (PPAR) α, carnitine palmitoyltransferase (CPT)-1, and pyruvate dehydrogenase kinase (PDK)-4 proteins and decreased the expression levels of myocardial PPARγ, glycerol-3-phosphate acyltransferase genes (GPAT), and glucose transporter (GLUT)-4 proteins. These findings demonstrated that apigenin could improve hypertensive cardiac hypertrophy and abnormal myocardial glucolipid metabolism in rats, and its mechanisms might be associated with the down-regulation of myocardial HIF-1α expression and, subsequently increasing the expressions of myocardial PPARα and its target genes CPT-1 and PDK-4, and decreasing the expressions of myocardial PPARγ and its target genes GPAT and GLUT-4. PMID:26987380

  2. Acute physiological stress down-regulates mRNA expressions of growth-related genes in coho salmon.

    Directory of Open Access Journals (Sweden)

    Toshiki Nakano

    Full Text Available Growth and development in fish are regulated to a major extent by growth-related factors, such as liver-derived insulin-like growth factor (IGF -1 in response to pituitary-secreted growth hormone (GH binding to the GH receptor (GHR. Here, we report on the changes in the expressions of gh, ghr, and igf1 genes and the circulating levels of GH and IGF-1 proteins in juvenile coho salmon (Oncorhynchus kisutch in response to handling as an acute physiological stressor. Plasma GH levels were not significantly different between stressed fish and prestressed control. Plasma IGF-1 concentrations in stressed fish 1.5 h post-stress were the same as in control fish, but levels in stressed fish decreased significantly 16 h post-stress. Real-time quantitative PCR (qPCR analysis showed that ghr mRNA levels in pituitary, liver, and muscle decreased gradually in response to the stressor. After exposure to stress, hepatic igf1 expression transiently increased, whereas levels decreased 16 h post-stress. On the other hand, the pituitary gh mRNA level did not change in response to the stressor. These observations indicate that expression of gh, ghr, and igf1 responded differently to stress. Our results show that acute physiological stress can mainly down-regulate the expressions of growth-related genes in coho salmon in vivo. This study also suggests that a relationship between the neuroendocrine stress response and growth-related factors exists in fish.

  3. MRP1 knockdown down-regulates the deposition of collagen and leads to a reduced hypertrophic scar fibrosis.

    Science.gov (United States)

    Li, Yan; Yang, Longlong; Zheng, Zhao; Shi, Jihong; Wu, Xue; Guan, Hao; Jia, Yanhui; Tao, Ke; Wang, Hongtao; Han, Shichao; Gao, Jianxin; Zhao, Bin; Su, Linlin; Hu, Dahai

    2015-10-01

    Multidrug resistance-associated protein 1 (MRP1) belongs to ATP-binding cassette transporters family. The overexpression of MRP1 is predominantly related with the failure of chemo-radiotherapy in various tumors. However, its possible role in hypertrophic scar (HS) is hardly investigated. Here we showed that the mRNA level and protein expression of MRP1 were higher in HS and HS derived fibroblasts (HSFs) than that in normal skin (NS) and NS derived fibroblasts (NSFs). Immunohistochemistry and immunofluorescence showed that the percentage of positive cells was higher in HS and HSFs. Meanwhile, the co-localization of MRP1 and α-SMA was stronger in HS. MRP1 knockdown in HSFs provoked a significant reduction in the protein expressions of collagen 3 and α-SMA in vitro. Moreover, MRP1 siRNA transfection could decrease the deposition of collagen in cultured tissues ex vivo and inhibit the scar formation in rabbit ear scar model in vivo. H&E staining and Masson trichrome staining revealed thinner and more orderly arranged collagen fiber in the MRP1 siRNA transfection group. The appearance of scar was improved as well. All these results indicate that MRP1 plays an important role in the formation of HS, MRP1 knockdown could be a potential method to reduce the accumulation of collagen and to improve the abnormal deposition of extracellular matrix in HS, which indicates that down-regulation of MRP1 has the potential therapeutic effect in the treatment and prophylaxis of HS.

  4. Characterization and Control of Airborne Particles Emitted During Production of Epoxy / Carbon Nanotube Nanocomposites

    Science.gov (United States)

    Cena, Lorenzo G.; Peters, Thomas M.

    2016-01-01

    This work characterized airborne particles that were generated from the weighing of bulk, multi-wall carbon nanotubes (CNTs) and the manual sanding of epoxy test samples reinforced with CNTs. It also evaluated the effectiveness of three local exhaust ventilation (LEV) conditions (no LEV, custom fume hood, and biosafety cabinet) for control of particles generated during sanding of CNT-epoxy nanocomposites. Particle number and respirable mass concentrations were measured using an optical particle counter (OPC) and a condensation particle counter (CPC), and particle morphology was assessed by transmission electron microscopy. The ratios of the geometric mean (GM) concentrations measured during the process to that measured in the background (P/B ratios) were used as indices of the impact of the process and the LEVs on observed concentrations. Processing CNT-epoxy nanocomposites materials released respirable size airborne particles (P/B ratio: weighing = 1.79; sanding = 5.90) but generally no nanoparticles (P/B ratiô1). The particles generated during sanding were predominately micron-sized with protruding CNTs and very different from bulk CNTs that tended to remain in large (>1 μm) tangled clusters. Respirable mass concentrations in the operator’s breathing zone were lower when sanding was performed in the biological safety cabinet (GM = 0.20 μg/m3) compared to those with no LEV (GM = 2.68 μg/m3) or those when sanding was performed inside the fume hood (GM = 21.4 μg/m3; p-value < 0.0001). The poor performance of the custom fume hood used in this study may have been exacerbated by its lack of a front sash and rear baffles and its low face velocity (0.39 m/sec). PMID:21253981

  5. Springtime carbon emission episodes at the Gosan background site revealed by total carbon, stable carbon isotopic composition, and thermal characteristics of carbonaceous particles

    Science.gov (United States)

    Jung, J.; Kawamura, K.

    2011-11-01

    In order to investigate the emission of carbonaceous aerosols at the Gosan background super-site (33.17° N, 126.10° E) in East Asia, total suspended particles (TSP) were collected during spring of 2007 and 2008 and analyzed for particulate organic carbon, elemental carbon, total carbon (TC), total nitrogen (TN), and stable carbon isotopic composition (δ13C) of TC. The stable carbon isotopic composition of TC (δ13CTC) was found to be lowest during pollen emission episodes (range: -26.2‰ to -23.5‰, avg. -25.2 ± 0.9‰), approaching those of the airborne pollen (-28.0‰) collected at the Gosan site. Based on a carbon isotope mass balance equation, we found that ~42% of TC in the TSP samples during the pollen episodes was attributed to airborne pollen from Japanese cedar trees planted around tangerine farms in Jeju Island. A negative correlation between the citric acid-carbon/TC ratios and δ13CTC was obtained during the pollen episodes. These results suggest that citric acid emitted from tangerine fruit may be adsorbed on the airborne pollen and then transported to the Gosan site. Thermal evolution patterns of organic carbon during the pollen episodes were characterized by high OC evolution in the OC2 temperature step (450 °C). Since thermal evolution patterns of organic aerosols are highly influenced by their molecular weight, they can be used as additional information on the formation of secondary organic aerosols and the effect of aging of organic aerosols during the long-range atmospheric transport and sources of organic aerosols.

  6. Springtime carbon emission episodes at the Gosan background site revealed by total carbon, stable carbon isotopic composition, and thermal characteristics of carbonaceous particles

    Directory of Open Access Journals (Sweden)

    J. Jung

    2011-11-01

    Full Text Available In order to investigate the emission of carbonaceous aerosols at the Gosan background super-site (33.17° N, 126.10° E in East Asia, total suspended particles (TSP were collected during spring of 2007 and 2008 and analyzed for particulate organic carbon, elemental carbon, total carbon (TC, total nitrogen (TN, and stable carbon isotopic composition (δ13C of TC. The stable carbon isotopic composition of TC (δ13CTC was found to be lowest during pollen emission episodes (range: −26.2‰ to −23.5‰, avg. −25.2 ± 0.9‰, approaching those of the airborne pollen (−28.0‰ collected at the Gosan site. Based on a carbon isotope mass balance equation, we found that ~42% of TC in the TSP samples during the pollen episodes was attributed to airborne pollen from Japanese cedar trees planted around tangerine farms in Jeju Island. A negative correlation between the citric acid-carbon/TC ratios and δ13CTC was obtained during the pollen episodes. These results suggest that citric acid emitted from tangerine fruit may be adsorbed on the airborne pollen and then transported to the Gosan site. Thermal evolution patterns of organic carbon during the pollen episodes were characterized by high OC evolution in the OC2 temperature step (450 °C. Since thermal evolution patterns of organic aerosols are highly influenced by their molecular weight, they can be used as additional information on the formation of secondary organic aerosols and the effect of aging of organic aerosols during the long-range atmospheric transport and sources of organic aerosols.

  7. Effect of Second-phase Particles on Static Adjustment of Calcite Grain Boundaries in Carbonate Mylonites

    Science.gov (United States)

    Ree, J.; Lee, S.; Jung, H.

    2010-12-01

    Static adjustment of grain boundaries during the waning stage of deformation with sustained heat (e.g. at the end of an orogeny) has not been studied much, although it is important for the interpretation of microstructural status during the main stage of deformation. We report here that static adjustment of calcite grain boundaries is dependent on second-phase particles in carbonate mylonites from the Geounri Shear Zone in the Taebaeksan Basin of South Korea. The carbonate mylonites consist of relic (porphyroclastic) calcites (120-400 μm) and dynamically recrystallized calcites (30-35 μm) with second-phase particles (15-20 μm) of quartz and phyllosilicates. Both calcite grains contain mechanical twins and the twins are wider (10-20 μm thick) in the relic calcites than in the dynamically recrystallized ones (1-3 μm thick). In the layers of carbonate mylonite with less than 3% of second phases, grain boundaries of calcites are straight with triple junctions. In contrast, calcite grain boundaries are lobate to wavy in the layers with more than 3% of second phases, suggesting dynamic grain boundary migration. Calcite grains in both layers show a strong lattice preferred orientation indicating dominant slip system of basal with minor one of rhomb . We interpret that the foam texture of calcite in the mylonite layers with less than 3% of second phases was produced during the waning stage of the main deformation with a sustained heat since both syntectonic and posttectonic chloritoid porphyroblasts occur in adjacent phyllonite layers in the shear zone. 3% volume fraction of second-phase particles might be a critical value above which deformation microstructures of the main phase were ‘frozen’ without static adjustment in our carbonate mylonites.

  8. Biological N2-fixation in Boreal Peatlands of Alberta Canada Following Acute N-Deposition: Down-Regulation and Subsequent Post-Recovery Projections.

    Science.gov (United States)

    Vile, M. A.; Fillingim, H.

    2015-12-01

    Globally, boreal peatlands cover a mere 3-4 % of the Earth's land surface, yet store ~ 30% of the world's soil carbon and ~9-16% of global soil nitrogen. Biological N2-fixation is the primary input of new nitrogen (N) to bogs in Alberta. We have demonstrated that this process is down regulated in the presence of enhanced atmospheric N deposition such as that from the growing Oil Sands Mining Operations in northern Alberta Canada. An important question for understanding the long term function of bogs in Alberta is whether N2-fixation can recover upon cessation of N pollution, and if so, how quickly? Here we present our preliminary findings in pursuit of this question. We measured rates of biological N2-fixation using the acetylene reduction assay (ARA), with subsequent calibration using 15N2 on separate, but paired incubations. Sphagnum fuscum from bogs at two different sites from northern Alberta were incubated over the course of 3 years, in 3 experimentally added treatments in the field; controls, plots receiving no added N and no water, water only treatments (no added N), and plots that were fertilized with N at a rate of 20 kg·ha-1·yr-1, and plots which had been fertilized with 20 kg·ha-1·yr-1in 2012-2013, but not since. In 2014, the rates of N2-fixation in the 20 kg·ha-1·yr-1plots and the recovering 20 kg·ha-1·yr-1plots were not significantly different, but both were significantly lower than the controls (p<0.05). In 2015, control plots had significantly higher rates of N2-fixation than the plots that had previously received 20 kg·ha-1·yr-1 in 2012 and 2013, and the plots that had not received 20 kg·ha-1·yr-1 since 2013 had significantly higher rates of biological N2-fixation. These data suggest that in a low atmospheric N deposition scenario, and over a short time frame, peatlands of northern Alberta may be able to recover from chronic atmospheric N deposition.

  9. Grinding Characteristic of Multi-walled Carbon Nanotubes-alumina Composite Particle

    Institute of Scientific and Technical Information of China (English)

    B MUNKHBAYAR; Nasan BAYARAA; Hafizur REHMAN; Junhyo KIM; Hanshik CHUNG; Hyomin JEONG

    2012-01-01

    The synthesis of new materials containing multi-walled carbon nanotubes (MWCNTs) and the microstructure of alumina particles were investigated and characterized.The MWCNTs and alumina particles were ground under both the dry and wet conditions with various rotation speeds (200-400 r/min) in planetary ball milling machine,and their combination characteristics were described.The experimental results were examined by scanning electron microscopy (SEM),X-ray diff action (XRD),transmission electron microscopy (TEM) and particle sizing analysis (PSA).SEM result revealed that the combination of MWCNTs -Alumina particles mixed quite well under both the dry and wet grinding with rotation speed of 400 r/min.XRD characterization indicated the better result could get in ground samples at a rotation speed of 400 r/min.PSA result showed the particle size decreased with increase the grinding speeds.From the overall results,we observed that the grinding method can be used to synthesize new material with high efficiency.

  10. [Comparison of Monitoring Methods of Organic Carbon and Element Carbon in Atmospheric Fine Particles].

    Science.gov (United States)

    Pang, Bo; Ji, Dong-sheng; Liu, Zi-rui; Zhu, Bin; Wang, Yue-si

    2016-04-15

    Accurate measurement of organic carbon (OC) and elemental carbon (EC) in atmospheric fine particulate is an important scientific basis for studying the formation and source apportionment of carbonaceous aerosol. The selection of different analysis programs will lead to difference in the OC and EC concentrations, and further result in the misjudgment of the results. The OC and EC concentrations observed using three temperature protocols including RT-Quartz ( R) , NIOSH 5040 (N) and Fast-TC (F) were compared and analyzed in combination with the degree of air pollution in Beijing. The results showed that there was no significant difference in the TC (TC = OC + EC), OC and EC concentrations observed using R, N and F protocols and certain deviation was found among the TC (TC = OC + EC) , OC and EC concentrations. For TC, the results observed using R protocol were 5% lower than those using N protocol; hut 1% higher than those using F protocol. For OC, the results obtained using R were 9% lower than those using N protocol and 1% higher than those using F protocol. For EC, the results obtained using R were 20% higher than those using N protocol and 11% lower than those using F protocol. The variation coefficients for TC, OC and EC obtained based on R protocol were less than the other two temperature protocols under different air quality degrees. The slopes of regression curves of TC, OC and EC between on-line analysis using R protocol and off-line analysis were 1.21,1. 14 and 1.35, respectively. The correlation coefficients of TC, OC and EC were 0.99, 0.99 and 0.98, respectively. In contrast with the Black carbon ( BC) concentrations monitored by multi-angle absorption spectrophotometer (MAAP), the EC concentrations measured by on-line OC/EC analyzer using R protocol were obviously lower. When the BC concentrations were less than or equal to 8 gg*m3, the EC/BC ratio was 0.39. While the EC/BC ratio was 0.88, when the BC concentrations were greater than 8 ggm3. The variation

  11. [Comparison of Monitoring Methods of Organic Carbon and Element Carbon in Atmospheric Fine Particles].

    Science.gov (United States)

    Pang, Bo; Ji, Dong-sheng; Liu, Zi-rui; Zhu, Bin; Wang, Yue-si

    2016-04-15

    Accurate measurement of organic carbon (OC) and elemental carbon (EC) in atmospheric fine particulate is an important scientific basis for studying the formation and source apportionment of carbonaceous aerosol. The selection of different analysis programs will lead to difference in the OC and EC concentrations, and further result in the misjudgment of the results. The OC and EC concentrations observed using three temperature protocols including RT-Quartz ( R) , NIOSH 5040 (N) and Fast-TC (F) were compared and analyzed in combination with the degree of air pollution in Beijing. The results showed that there was no significant difference in the TC (TC = OC + EC), OC and EC concentrations observed using R, N and F protocols and certain deviation was found among the TC (TC = OC + EC) , OC and EC concentrations. For TC, the results observed using R protocol were 5% lower than those using N protocol; hut 1% higher than those using F protocol. For OC, the results obtained using R were 9% lower than those using N protocol and 1% higher than those using F protocol. For EC, the results obtained using R were 20% higher than those using N protocol and 11% lower than those using F protocol. The variation coefficients for TC, OC and EC obtained based on R protocol were less than the other two temperature protocols under different air quality degrees. The slopes of regression curves of TC, OC and EC between on-line analysis using R protocol and off-line analysis were 1.21,1. 14 and 1.35, respectively. The correlation coefficients of TC, OC and EC were 0.99, 0.99 and 0.98, respectively. In contrast with the Black carbon ( BC) concentrations monitored by multi-angle absorption spectrophotometer (MAAP), the EC concentrations measured by on-line OC/EC analyzer using R protocol were obviously lower. When the BC concentrations were less than or equal to 8 gg*m3, the EC/BC ratio was 0.39. While the EC/BC ratio was 0.88, when the BC concentrations were greater than 8 ggm3. The variation

  12. Adsorption capacities of activated carbons for geosmin and 2-methylisoborneol vary with activated carbon particle size: Effects of adsorbent and adsorbate characteristics.

    Science.gov (United States)

    Matsui, Yoshihiko; Nakao, Soichi; Sakamoto, Asuka; Taniguchi, Takuma; Pan, Long; Matsushita, Taku; Shirasaki, Nobutaka

    2015-11-15

    The adsorption capacities of nine activated carbons for geosmin and 2-methylisoborneol (MIB) were evaluated. For some carbons, adsorption capacity substantially increased when carbon particle diameter was decreased from a few tens of micrometers to a few micrometers, whereas for other carbons, the increase of adsorption capacity was small for MIB and moderate for geosmin. An increase of adsorption capacity was observed for other hydrophobic adsorbates besides geosmin and MIB, but not for hydrophilic adsorbates. The parameter values of a shell adsorption model describing the increase of adsorption capacity were negatively correlated with the oxygen content of the carbon among other characteristics. Low oxygen content indicated low hydrophilicity. The increase of adsorption capacity was related to the hydrophobic properties of both adsorbates and activated carbons. For adsorptive removal of hydrophobic micropollutants such as geosmin, it is therefore recommended that less-hydrophilic activated carbons, such as coconut-shell-based carbons, be microground to a particle diameter of a few micrometers to enhance their equilibrium adsorption capacity. In contrast, adsorption by hydrophilic carbons or adsorption of hydrophilic adsorbates occur in the inner pores, and therefore adsorption capacity is unchanged by particle size reduction. PMID:26302219

  13. Adsorption capacities of activated carbons for geosmin and 2-methylisoborneol vary with activated carbon particle size: Effects of adsorbent and adsorbate characteristics.

    Science.gov (United States)

    Matsui, Yoshihiko; Nakao, Soichi; Sakamoto, Asuka; Taniguchi, Takuma; Pan, Long; Matsushita, Taku; Shirasaki, Nobutaka

    2015-11-15

    The adsorption capacities of nine activated carbons for geosmin and 2-methylisoborneol (MIB) were evaluated. For some carbons, adsorption capacity substantially increased when carbon particle diameter was decreased from a few tens of micrometers to a few micrometers, whereas for other carbons, the increase of adsorption capacity was small for MIB and moderate for geosmin. An increase of adsorption capacity was observed for other hydrophobic adsorbates besides geosmin and MIB, but not for hydrophilic adsorbates. The parameter values of a shell adsorption model describing the increase of adsorption capacity were negatively correlated with the oxygen content of the carbon among other characteristics. Low oxygen content indicated low hydrophilicity. The increase of adsorption capacity was related to the hydrophobic properties of both adsorbates and activated carbons. For adsorptive removal of hydrophobic micropollutants such as geosmin, it is therefore recommended that less-hydrophilic activated carbons, such as coconut-shell-based carbons, be microground to a particle diameter of a few micrometers to enhance their equilibrium adsorption capacity. In contrast, adsorption by hydrophilic carbons or adsorption of hydrophilic adsorbates occur in the inner pores, and therefore adsorption capacity is unchanged by particle size reduction.

  14. Springtime carbon episodes at Gosan background site revealed by total carbon, stable carbon isotopic composition, and thermal characteristics of carbonaceous particles

    Science.gov (United States)

    Jung, J.; Kawamura, K.

    2011-05-01

    In order to investigate the carbon episodes at Gosan background super-site (33.17° N, 126.10° E) in East Asia during spring of 2007 and 2008, total suspended particles (TSP) were collected and analyzed for particulate organic carbon, elemental carbon, total carbon (TC), total nitrogen (TN), and stable carbon isotopic composition (δ13C) of TC. The carbon episodes at the Gosan site were categorized as long-range transported anthropogenic pollutant (LTP) from Asian continent, Asian dust (AD) accompanying with LTP, and local pollen episodes. The stable carbon isotopic composition of TC (δ13CTC) was found to be lowest during the pollen episodes (range: -26.2 ‰ to -23.5 ‰, avg.: -25.2 ± 0.9 ‰), followed by the LTP episodes (range: -23.5 ‰ to -23.0 ‰, avg.: -23.3 ± 0.3 ‰) and the AD episodes (range: -23.3 to -20.4 %, avg.: -21.8 ± 2.0 ‰). The δ13CTC of the airborne pollens (-28.0 ‰) collected at the Gosan site showed value similar to that of tangerine fruit (-28.1 ‰) produced from Jeju Island. Based on the carbon isotope mass balance equation and the TN and TC regression approach, we found that ∼40-45 % of TC in the TSP samples during the pollen episodes was attributed to airborne pollens from Japanese cedar trees planted around tangerine farms in Jeju Island. The δ13C of citric acid in the airborne pollens (-26.3 ‰) collected at the Gosan site was similar to that in tangerine fruit (-27.4 ‰). The negative correlation between the citric acid-carbon/TC ratios and δ13CTC were obtained during the pollen episodes. These results suggest that citric acid emitted from tangerine fruit may be adsorbed on the airborne pollens and then transported to the Gosan site. Based on the thermal evolution pattern of organic aerosols during the carbon episodes, we found that organic aerosols originated from East China are more volatile on heating and are more likely to form pyrolized organic carbon than the pollen-enriched organic aerosols and organic

  15. In-situ observation of sputtered particles for carbon implanted tungsten during energetic isotope ion implantation

    Energy Technology Data Exchange (ETDEWEB)

    Oya, Y.; Sato, M.; Uchimura, H.; Okuno, K. [Graduate School of Science, Shizuoka University, Shizuoka (Japan); Ashikawa, N.; Sagara, A. [National Institute for Fusion Science, Gifu (Japan); Yoshida, N. [Institute for Applied Mechanics, Kyushu University, Kasuga (Japan); Hatano, Y. [Hydrogen Isotope Research Center, University of Toyama, Toyama (Japan)

    2015-03-15

    Tungsten is a candidate for plasma facing materials in future fusion reactors. During DT plasma operations, carbon as an impurity will bombard tungsten, leading to the formation of tungsten-carbon (WC) layer and affecting tritium recycling behavior. The effect of carbon implantation for the dynamic recycling of deuterium, which demonstrates tritium recycling, including retention and sputtering, has been investigated using in-situ sputtered particle measurements. The C{sup +} implanted W, WC and HOPG were prepared and dynamic sputtered particles were measured during H{sub 2}{sup +} irradiation. It has been found that the major hydrocarbon species for C{sup +} implanted tungsten is CH{sub 3}, while for WC and HOPG (Highly Oriented Pyrolytic Graphite) it is CH{sub 4}. The chemical state of hydrocarbon is controlled by the H concentration in a W-C mixed layer. The amount of C-H bond and the retention of H trapped by carbon atom should control the chemical form of hydrocarbon sputtered by H{sub 2}{sup +} irradiation and the desorption of CH{sub 3} and CH{sub 2} are due to chemical sputtering, although that for CH is physical sputtering. The activation energy for CH{sub 3} desorption has been estimated to be 0.4 eV, corresponding to the trapping process of hydrogen by carbon through the diffusion in W. It is concluded that the chemical states of hydrocarbon sputtered by H{sub 2}{sup +} irradiation for W is determined by the amount of C-H bond on the W surface. (authors)

  16. Mechanism of Methylene Blue adsorption on hybrid laponite-multi-walled carbon nanotube particles.

    Science.gov (United States)

    Manilo, Maryna; Lebovka, Nikolai; Barany, Sandor

    2016-04-01

    The kinetics of adsorption and parameters of equilibrium adsorption of Methylene Blue (MB) on hybrid laponite-multi-walled carbon nanotube (NT) particles in aqueous suspensions were determined. The laponite platelets were used in order to facilitate disaggregation of NTs in aqueous suspensions and enhance the adsorption capacity of hybrid particles for MB. Experiments were performed at room temperature (298K), and the laponite/NT ratio (Xl) was varied in the range of 0-0.5. For elucidation of the mechanism of MB adsorption on hybrid particles, the electrical conductivity of the system as well as the electrokinetic potential of laponite-NT hybrid particles were measured. Three different stages in the kinetics of adsorption of MB on the surface of NTs or hybrid laponite-NT particles were discovered to be a fast initial stage I (adsorption time t=0-10min), a slower intermediate stage II (up to t=120min) and a long-lasting final stage III (up to t=24hr). The presence of these stages was explained accounting for different types of interactions between MB and adsorbent particles, as well as for the changes in the structure of aggregates of NT particles and the long-range processes of restructuring of laponite platelets on the surface of NTs. The analysis of experimental data on specific surface area versus the value of Xl evidenced in favor of the model with linear contacts between rigid laponite platelets and NTs. It was also concluded that electrostatic interactions control the first stage of adsorption at low MB concentrations. PMID:27090704

  17. Markedly enhanced direct radiative forcing of black carbon particles under polluted urban environments

    Science.gov (United States)

    Peng, Jianfei; Hu, Min; Guo, Song; Du, Zhuofei; Zheng, Jing; Shang, Dongjie; Zamora, Misti; Zeng, Liming; Shao, Min; Wu, Yusheng; Zheng, Jun; Wang, Yuan; Collins, Don; Zhang, Renyi

    2016-04-01

    Black carbon (BC) particles, produced from incomplete fossil fuel combustion and biomass burning, are ubiquitous in the atmosphere and have profound impacts on air quality, human health, weather, and climate. For example, in areas identified as aerosol hotspots, which include many urban centers and megacities worldwide, solar heating by BC particles has been shown to be comparable to warming due to the greenhouse gases2. Although BC represents a key short-lived climate forcer, its direct radiative forcing remains highly uncertain. In particular, the available results of absorption enhancement of BC particles during atmospheric aging are conflicting from the previous studies, leading to a large uncertainty in global radiative transfer calculation. Here, we quantified the aging and variation in the optical properties of BC particles under ambient conditions in Beijing, China and Houston, US, using a novel chamber approach. BC aging exhibits two distinct stages - initial transformation from a fractal to spherical morphology with little absorption variation and the subsequent growth of fully compact particles with a maximum absorption enhancement factor of 2.4. The variation in BC direct radiative forcing is highly dependent of the rate and timescale of aging, with an estimated increase of 0.45 (0.21 - 0.80) W m-2 from fresh to fully aged particles. Our results reveal a high climatic impact in polluted environments due to rapid aging and a clear distinction between urban cities in developed and developing countries for BC particles, highlighting a larger than recognized co-benefit in air quality improvement and climate protection by BC mediation.

  18. Sn-Pb and lead free solders containing active carbon particles

    Science.gov (United States)

    Talas, S.; Gökçe, B.; Çakmakkaya, M.

    2016-08-01

    Upon the legislations issued by the governmental agencies, many companies are in effort of using lead free solders for their electronic products. Many researchers have also focused on lead free solders and determined their physical properties to the merit of their desired strength and conductivity which turns out to be a potentially advantageous after all. The addition of nano particles into the solder alloys has been attempted to investigate the property change caused by such addition from which a main outcome was a limited improved mechanical and physical properties such as lowering the melting temperature. In this study, the addition of nano active carbon particles to Pb-Sn and Pb-free solder alloys were made and characterization studies were conducted to determine their basic properties such as electrical conductivity, microstructural study and also phase transformations. The results indicate that the addition of active carbon particles brings about a change in thermal properties more markedly than other properties with respect to the amount of addition.

  19. Electrochemical characterisation of activated carbon particles used in redox flow battery electrodes

    Science.gov (United States)

    Radford, G. J. W.; Cox, J.; Wills, R. G. A.; Walsh, F. C.

    The Faradaic and non-Faradaic characteristics of a series of activated carbon particles (used to produce composite carbon-polymer electrodes for redox flow cells) have been determined using aqueous electrolytes (sulfuric acid and sodium polysulfide) at 295 K. The particles were mounted as a circular section (ca. 0.80 cm 2) shallow packed bed of 2.5 mm thickness in the direction of electrolyte flow (mean linear flow velocity ≈ 6 mm s -1). Cyclic voltammetry in deaerated, 1 mol dm -3 H 2SO 4 at 295 K indicated a specific capacitance in the range of 50-140 F g -1. Linear sweep voltammetry and galvanostatic step studies in an alkaline sodium polysulfide electrolyte (1.8 mol dm -3 Na 2S 2.11) have demonstrated marked differences amongst various types of activated carbon. Such differences are highlighted during galvanostatic charge-discharge cycling of half-cell electrodes in the polysulfide electrolyte. The electrochemical characteristics are compared to those based on (N 2 adsorption) gas porosimetry measurements.

  20. Hyperbranched Aliphatic Polyester Modified Activated Carbon Particles with Homogenized Surface Groups

    Science.gov (United States)

    Liu, Peng; Zhang, Liuxue

    The hyperbranched aliphatic polyester grafted activated carbon (HAPE-AC), was successfully prepared by the simple "one-pot" method. The surface functional groups of commercial activated carbon particles were homogenized to hydroxyl groups by being oxidized with nitric acid and then reduced with lithium tetrahydroaluminate (LiAlH4) at first. Secondly, the surface hydroxyl groups were used as the active sites for the solution polycondensation of the AB2 monomer, 2, 2-bis(hydroxymethyl)propionic acid (bis-MPA), with the catalysis of p-toluenesulfonic acid (p-TSA). The homogenization of the surface groups of the activated carbon particles and the graft polymerization of the hyperbranched aliphatic polyester were investigated by X-ray photoelectron spectroscopy (XPS) technique. The products were also characterized with Fourier transform infrared (FT-IR) and scanning electron microscope (SEM). The competitive adsorption properties of the products toward the heavy metal ions (Cu(II), Hg(II), Zn(II), and Cd(II)) also proved the translations of the surface groups.

  1. Diagnosis of laser ablated carbon particles measured by time-resolved X-ray absorption spectroscopy

    International Nuclear Information System (INIS)

    The time and space resolved properties of laser ablated carbon particles were measured by X-ray absorption spectroscopy using LPX as an X-ray source. The energy density of the irradiation laser on the sample was in the range of 0.5-20J/cm2 and the time delay was varied between 0 and 120ns. The absorption spectra exhibited several peaks originated from level to level transitions and an intense broad absorption in the energy range of C-K edge. At a delay time of 120ns, the absorption peak from 1s→2p transition of neutral carbon atom (C0), C-, C+ and C2+ ions were observed. The absorption peak from C0 was stronger as the probing position was closer to the sample surface and decreased rapidly with distance from the sample surface. The absorption peak C2+ ion was observed only at comparatively distant positions from surface. The maximum speeds of highly charged ions were faster than that of neutral atoms and negative charged ions. The neutral atom and lower charged ions were emitted from the sample even after laser irradiation. The spatial distributions of the laser ablated carbon particles in the localized helium gas environment were measured. In the helium gas environment, the ablation plume was depressed by the helium cloud generated on the top of ablation plume. (author)

  2. Carbon-based phytoplankton size classes retrieved via ocean color estimates of the particle size distribution

    Science.gov (United States)

    Kostadinov, Tihomir S.; Milutinović, Svetlana; Marinov, Irina; Cabré, Anna

    2016-04-01

    Owing to their important roles in biogeochemical cycles, phytoplankton functional types (PFTs) have been the aim of an increasing number of ocean color algorithms. Yet, none of the existing methods are based on phytoplankton carbon (C) biomass, which is a fundamental biogeochemical and ecological variable and the "unit of accounting" in Earth system models. We present a novel bio-optical algorithm to retrieve size-partitioned phytoplankton carbon from ocean color satellite data. The algorithm is based on existing methods to estimate particle volume from a power-law particle size distribution (PSD). Volume is converted to carbon concentrations using a compilation of allometric relationships. We quantify absolute and fractional biomass in three PFTs based on size - picophytoplankton (0.5-2 µm in diameter), nanophytoplankton (2-20 µm) and microphytoplankton (20-50 µm). The mean spatial distributions of total phytoplankton C biomass and individual PFTs, derived from global text">SeaWiFS monthly ocean color data, are consistent with current understanding of oceanic ecosystems, i.e., oligotrophic regions are characterized by low biomass and dominance of picoplankton, whereas eutrophic regions have high biomass to which nanoplankton and microplankton contribute relatively larger fractions. Global climatological, spatially integrated phytoplankton carbon biomass standing stock estimates using our PSD-based approach yield ˜ 0.25 Gt of C, consistent with analogous estimates from two other ocean color algorithms and several state-of-the-art Earth system models. Satisfactory in situ closure observed between PSD and POC measurements lends support to the theoretical basis of the PSD-based algorithm. Uncertainty budget analyses indicate that absolute carbon concentration uncertainties are driven by the PSD parameter No which determines particle number concentration to first order, while uncertainties in PFTs' fractional contributions to total C biomass are mostly due to the

  3. Carbon-based phytoplankton size classes retrieved via ocean color estimates of the particle size distribution

    Science.gov (United States)

    Kostadinov, Tihomir S.; Milutinović, Svetlana; Marinov, Irina; Cabré, Anna

    2016-04-01

    Owing to their important roles in biogeochemical cycles, phytoplankton functional types (PFTs) have been the aim of an increasing number of ocean color algorithms. Yet, none of the existing methods are based on phytoplankton carbon (C) biomass, which is a fundamental biogeochemical and ecological variable and the "unit of accounting" in Earth system models. We present a novel bio-optical algorithm to retrieve size-partitioned phytoplankton carbon from ocean color satellite data. The algorithm is based on existing methods to estimate particle volume from a power-law particle size distribution (PSD). Volume is converted to carbon concentrations using a compilation of allometric relationships. We quantify absolute and fractional biomass in three PFTs based on size - picophytoplankton (0.5-2 µm in diameter), nanophytoplankton (2-20 µm) and microphytoplankton (20-50 µm). The mean spatial distributions of total phytoplankton C biomass and individual PFTs, derived from global SeaWiFS monthly ocean color data, are consistent with current understanding of oceanic ecosystems, i.e., oligotrophic regions are characterized by low biomass and dominance of picoplankton, whereas eutrophic regions have high biomass to which nanoplankton and microplankton contribute relatively larger fractions. Global climatological, spatially integrated phytoplankton carbon biomass standing stock estimates using our PSD-based approach yield ˜ 0.25 Gt of C, consistent with analogous estimates from two other ocean color algorithms and several state-of-the-art Earth system models. Satisfactory in situ closure observed between PSD and POC measurements lends support to the theoretical basis of the PSD-based algorithm. Uncertainty budget analyses indicate that absolute carbon concentration uncertainties are driven by the PSD parameter No which determines particle number concentration to first order, while uncertainties in PFTs' fractional contributions to total C biomass are mostly due to the

  4. Arrow plot: a new graphical tool for selecting up and down regulated genes and genes differentially expressed on sample subgroups

    Directory of Open Access Journals (Sweden)

    Silva-Fortes Carina

    2012-06-01

    Full Text Available Abstract Background A common task in analyzing microarray data is to determine which genes are differentially expressed across two (or more kind of tissue samples or samples submitted under experimental conditions. Several statistical methods have been proposed to accomplish this goal, generally based on measures of distance between classes. It is well known that biological samples are heterogeneous because of factors such as molecular subtypes or genetic background that are often unknown to the experimenter. For instance, in experiments which involve molecular classification of tumors it is important to identify significant subtypes of cancer. Bimodal or multimodal distributions often reflect the presence of subsamples mixtures. Consequently, there can be genes differentially expressed on sample subgroups which are missed if usual statistical approaches are used. In this paper we propose a new graphical tool which not only identifies genes with up and down regulations, but also genes with differential expression in different subclasses, that are usually missed if current statistical methods are used. This tool is based on two measures of distance between samples, namely the overlapping coefficient (OVL between two densities and the area under the receiver operating characteristic (ROC curve. The methodology proposed here was implemented in the open-source R software. Results This method was applied to a publicly available dataset, as well as to a simulated dataset. We compared our results with the ones obtained using some of the standard methods for detecting differentially expressed genes, namely Welch t-statistic, fold change (FC, rank products (RP, average difference (AD, weighted average difference (WAD, moderated t-statistic (modT, intensity-based moderated t-statistic (ibmT, significance analysis of microarrays (samT and area under the ROC curve (AUC. On both datasets all differentially expressed genes with bimodal or multimodal

  5. Down-regulated βIII-tubulin Expression Can Reverse Paclitaxel Resistance in A549/Taxol Cells Lines

    Directory of Open Access Journals (Sweden)

    Yinling ZHUO

    2014-08-01

    Full Text Available Background and objective Chemotherapy drug resistance is the primary causes of death in patients with pulmonary carcinoma which make tumor recurrence or metastasis. β-tubulin is the main cell targets of anti-microtubule drug. Increased expression of βIII-tubulin has been implicated in non-small cell lung cancer (NSCLC cell lines. To explore the relationship among the expression level of βIII-tubulin and the sensitivity of A549/Taxolcell lines to Taxol and cell cycles and cell apoptosis by RNA interference-mediated inhibition of βIII-tubulin in A549/Taxol cells. Methods Three pairs of siRNA targetd βIII-tubulin were designed and prepared, which were transfected into A549/Taxol cells using LipofectamineTM 2000. We detected the expression of βIII-tubulin mRNA using Real-time fluorescence qRT-PCR. Tedhen we selected the most efficient siRNA by the expression of βIII-tubulin mRNA in transfected group. βIII-tubulin protein level were mesured by Western blot. The taxol sensitivity in transfected group were evaluated by MTT assay. And the cell apoptosis and cell cycles were determined by flow cytometry. Results βIII-tubulin mRNA levels in A549/Taxol cells were significantly decreased in transfected grop by Real-time qRT-PCR than control groups. And βIII-tubulin siRNA-1 sequence showed the highest transfection efficiency, which was (87.73±4.87% (P<0.01; Western blot results showed that the expressional level of BIII tublin protein was significantly down-reulated in the transfectant cells than thant in the control cells. By MTT assay, we showed that the inhibition ratio of Taxol to A549/Taxol cells transfeced was higher than that of control group (51.77±4.60% (P<0.01. The early apoptosis rate of A549/Taxol cells in transfected group were significantly higher than that of control group (P<0.01; G2-M content in taxol group obviously increased than untreated samples by the cell cycle (P<0.05. Conclusion βIII-tubulin down-regulated significantly

  6. Atherosclerosis-Associated Endothelial Cell Apoptosis by MiR-429-Mediated Down Regulation of Bcl-2

    Directory of Open Access Journals (Sweden)

    Tao Zhang

    2015-10-01

    -associated endothelial cell apoptosis may result from down regulation of Bcl-2, through increased miR-429 that binds and suppresses translation of Bcl-2 mRNA.

  7. Elevated expression of prostate cancer-associated genes is linked to down-regulation of microRNAs

    International Nuclear Information System (INIS)

    Recent evidence suggests that the prostate cancer (PCa)-specific up-regulation of certain genes such as AMACR, EZH2, PSGR, PSMA and TRPM8 could be associated with an aberrant expression of non-coding microRNAs (miRNA). In silico analyses were used to search for miRNAs being putative regulators of PCa-associated genes. The expression of nine selected miRNAs (hsa-miR-101, -138, -186, -224, -26a, -26b, -374a, -410, -660) as well as of the aforementioned PCa-associated genes was analyzed by quantitative PCR using 50 malignant (Tu) and matched non-malignant (Tf) tissue samples from prostatectomy specimens as well as 30 samples from patients with benign prostatic hyperplasia (BPH). Then, correlations between paired miRNA and target gene expression levels were analyzed. Furthermore, the effect of exogenously administered miR-26a on selected target genes was determined by quantitative PCR and Western Blot in various PCa cell lines. A luciferase reporter assay was used for target validation. The expression of all selected miRNAs was decreased in PCa tissue samples compared to either control group (Tu vs Tf: -1.35 to -5.61-fold; Tu vs BPH: -1.17 to -5.49-fold). The down-regulation of most miRNAs inversely correlated with an up-regulation of their putative target genes with Spearman correlation coefficients ranging from -0.107 to -0.551. MiR-186 showed a significantly diminished expression in patients with non-organ confined PCa and initial metastases. Furthermore, over-expression of miR-26a reduced the mRNA and protein expression of its potential target gene AMACR in vitro. Using the luciferase reporter assay AMACR was validated as new target for miR-26a. The findings of this study indicate that the expression of specific miRNAs is decreased in PCa and inversely correlates with the up-regulation of their putative target genes. Consequently, miRNAs could contribute to oncogenesis and progression of PCa via an altered miRNA-target gene-interaction

  8. Kaempferol enhances cisplatin's effect on ovarian cancer cells through promoting apoptosis caused by down regulation of cMyc

    Directory of Open Access Journals (Sweden)

    Jiang Bing-Hua

    2010-05-01

    Full Text Available Abstract Background Ovarian cancer is one of the most significant malignancies in the western world. Studies showed that Ovarian cancers tend to grow resistance to cisplatin treatment. Therefore, new approaches are needed in ovarian cancer treatment. Kaempferol is a dietary flavonoid that is widely distributed in fruits and vegetables, and epidemiology studies have revealed a protective effect of kaempferol against ovarian cancer risk. Our early studies also found that kaempferol is effective in reducing vascular endothelial growth factor (VEGF expression in ovarian cancer cells. In this study, we investigated kaempferol's effects on sensitizing ovarian cancer cell growth in response to cisplatin treatment. Results Ten chemicals were screened for sensitizing OVCAR-3 ovarian cancer cell growth in response to cisplatin treatment. For kaempferol, which shows a significant synergistic interaction with cisplatin, expression of ABCC1, ABCC5, ABCC6, NFkB1, cMyc, and CDKN1A genes was further examined. For cisplatin/kaempferol treatments on OVCAR-3 cancer cells, the mRNA levels of ABCC1, ABCC5, and NFkB1 did not change. However, significant inhibition of ABCC6 and cMyc mRNA levels was observed for the cisplatin/kaempferol combined treatment. The CDKN1A mRNA levels were significantly up-regulated by cisplatin/kaempferol treatment. A plot of CDKN1A mRNA levels against that of cMyc gene further revealed a reverse, linear relationship, proving cMyc's regulation on CDKN1A gene expressions. Our work found that kaempferol works synergistically with cisplatin in inhibiting ovarian cancer cell viability, and their inhibition on cell viabilities was induced through inhibiting ABCC6 and cMyc gene transcription. Apoptosis assay showed the addition of 20 μM kaempferol to the cisplatin treatment induces the apoptosis of the cancer cells. Conclusions Kaempferol enhances the effect of cisplatin through down regulation of cMyc in promoting apoptosis of ovarian cancer

  9. Resveratrol Induced Premature Senescence Is Associated with DNA Damage Mediated SIRT1 and SIRT2 Down-Regulation.

    Directory of Open Access Journals (Sweden)

    Mehtap Kilic Eren

    agent doxorubicin also induced senescence in BJ fibroblasts associated with decreased SIRT1/2 levels. In conclusion our data reveal that resveratrol induced premature senescence is associated with SIRT1 and SIRT2 down regulation in human dermal fibroblasts. Here we suggest that the concomitant decline in SIRT1/2 expression in response to resveratrol treatment may be a cause for induction of senescence, which is most likely mediated by a regulatory mechanism activated by DNA damage response.

  10. Transcriptional down regulation of hTERT and senescence induction in HepG2 cells by chelidonine

    Institute of Scientific and Technical Information of China (English)

    Sakineh Kazemi Noureini; Michael Wink

    2009-01-01

    aged with large volume and dark staining in the β-galactosidase assay. CONCLUSION: Chelidonine reduces telomerase activity through down-regulation of hTERT expression. Senescence induction might not be directly caused by reducing telomerase activity as it occurs after a few population doublings.

  11. Gonadotropin Inhibitory Hormone Down-Regulates the Brain-Pituitary Reproductive Axis of Male European Sea Bass (Dicentrarchus labrax).

    Science.gov (United States)

    Paullada-Salmerón, José A; Cowan, Mairi; Aliaga-Guerrero, María; Morano, Francesca; Zanuy, Silvia; Muñoz-Cueto, José A

    2016-06-01

    Gonadotropin-inhibitory hormone (GnIH) inhibits gonadotropin synthesis and release from the pituitary of birds and mammals. However, the physiological role of orthologous GnIH peptides on the reproductive axis of fish is still uncertain, and their actions on the main neuroendocrine systems controlling reproduction (i.e., GnRHs, kisspeptins) have received little attention. In a recent study performed in the European sea bass, we cloned a cDNA encoding a precursor polypeptide that contained C-terminal MPMRFamide (sbGnIH-1) and MPQRFamide (sbGnIH-2) peptide sequences, developed a specific antiserum against sbGnIH-2, and characterized its central and pituitary GnIH projections in this species. In this study, we analyzed the effects of intracerebroventricular injection of sbGnIH-1 and sbGnIH-2 on brain and pituitary expression of reproductive hormone genes (gnrh1, gnrh2, gnrh3, kiss1, kiss2, gnih, lhbeta, fshbeta), and their receptors (gnrhr II-1a, gnrhr II-2b, kiss1r, kiss2r, and gnihr) as well as on plasma Fsh and Lh levels. In addition, we determined the effects of GnIH on pituitary somatotropin (Gh) expression. The results obtained revealed the inhibitory role of sbGnIH-2 on brain gnrh2, kiss1, kiss2, kiss1r, gnih, and gnihr transcripts and on pituitary fshbeta, lhbeta, gh, and gnrhr-II-1a expression, whereas sbGnIH-1 only down-regulated brain gnrh1 expression. However, at different doses, central administration of both sbGnIH-1 and sbGnIH-2 decreased Lh plasma levels. Our work represents the first study reporting the effects of centrally administered GnIH in fish and provides evidence of the differential actions of sbGnIH-1 and sbGnIH-2 on the reproductive axis of sea bass, the main inhibitory role being exerted by the sbGnIH-2 peptide. PMID:26984999

  12. Black Carbon Particle Number Distribution Measurements during the ATHENS-2013 Winter Campaign

    Science.gov (United States)

    Gkatzelis, Georgios; Papanastasiou, Dimitris; Florou, Kalliopi; Kaltsonoudis, Christos; Louvaris, Eyaggelos; Bezentakos, Spiridon; Biskos, Georgios; Pandis, Spuros

    2014-05-01

    Black Carbon (BC) particles emitted by anthropogenic sources play an important role both in climate change and in air quality degradation. Open burning in forests and savannas, combustion of diesel and solid fuels for cooking and heating in homes represent the majority of BC emissions. Earlier work has focused on the BC atmospheric direct radiative forcing that is mostly related to its mass concentration and optical properties of the corresponding particles. A variety of measurement techniques are used to measure the mass concentration of BC by taking advantage of its optical or physical properties. Moreover, the carbonaceous particles containing BC are also important for the indirect forcing of climate. This effect is mostly related to the number concentration of BC particles. The number distribution of BC particles especially below 100 nm is quite uncertain due to limitations of the existing measurement techniques. In this work we employed a thermodenuder-based method as an approach for the measurement of the BC number distribution. More specifically, we combined a thermodenuder (TD) operating at temperatures up to 300 ° C, with a Scanning Mobility Particle Sizer (SMPS) and a High Resolution Time of Flight Aerosol Mass Spectrometer (HR-ToF AMS). Aerosol size and composition measurements were carried out both at ambient and at elevated TD temperatures in Athens field campaign during January and February of 2013. In parallel, a Multi-Angle Absorption Photometer (MAAP) provided information about the BC mass concentration while a Hygroscopic Tandem Differential Mobility Analyzer (HTDMA) measured the mixing state and the hygroscopicity of the particles as a function of their size. These measurements were then combined to estimate the number concentration of BC particles. Our analysis focused on different periods during the study. During some of them one source dominated the carbonaceous aerosol concentration. Such periods included rush hour traffic, nighttime wood

  13. Cobalt oxide and nitride particles supported on mesoporous carbons as composite electrocatalysts for dye-sensitized solar cells

    Science.gov (United States)

    Chen, Ming; Shao, Leng-Leng; Gao, Ze-Min; Ren, Tie-Zhen; Yuan, Zhong-Yong

    2015-07-01

    The composite electrocatalysts of cobalt oxide/mesoporous carbon and cobalt nitride/mesoporous carbon are synthesized via a convenient oxidation and subsequent ammonia nitridation of cobalt particles-incorporated mesoporous carbon, respectively. The cobalt oxide and nitride particles are uniformly imbedded in mesoporous carbon matrix, forming the unique composites with high surface area and mesopore architecture, and the resultant composites are evaluated as counter electrode materials, exhibiting good catalytic activity for the reduction of triiodide. The composites of cobalt nitride and mesoporous carbon are superior to the counterparts of cobalt oxide and mesoporous carbon in catalyzing the triiodide reduction, and the dye-sensitized solar cell with the composites achieves an optimum power conversion efficiency of 5.26%, which is comparable to the one based on the conventional Pt counter electrode (4.88%).

  14. Carbon Aerogel-Supported Pt Catalysts for the Hydrogenolysis and Isomerization of n-Butane: Influence of the Carbonization Temperature of the Support and Pt Particle Size

    Directory of Open Access Journals (Sweden)

    Marta B. Dawidziuk

    2012-10-01

    Full Text Available Carbon aerogels prepared at different carbonization temperatures and with varying mesopore volumes were used as supports for Pt catalysts to study the n-C4H10/H2 reaction. Mean Pt particle size depended on the mesopore volume of the support, showing a linear decrease when the mesopore volume increased. The turnover frequency (TOF for hydrogenolysis was much higher than for isomerization in catalysts supported on carbon aerogels obtained at 900–950 °C. However, both TOF values were similar in catalysts supported on the carbon aerogel obtained at 500 °C. TOF for hydrogenolysis and isomerization were related to the mean Pt particle size in catalysts supported on carbon aerogels obtained at 900–950 °C. In addition, both reactions showed a compensation effect between the activation energy and pre-exponential factor, indicating that they have the same intermediate, i.e., the chemisorbed dehydrogenated alkane.

  15. Carbon species in PM10 particle fraction at different monitoring sites.

    Science.gov (United States)

    Godec, Ranka; Jakovljević, Ivana; Šega, Krešimir; Čačković, Mirjana; Bešlić, Ivan; Davila, Silvije; Pehnec, Gordana

    2016-09-01

    The aim of this study was to determine and compare the levels of elemental carbon (EC), organic carbon (OC) and polycyclic aromatic hydrocarbons (PAHs) mass concentrations in PM10 particles (particles with aerodynamic diameter less than 10 μm) between seasons (winter and summer) and at different monitoring sites (urban background and rural industrial). Daily samples of airborne particles were collected on pre-fired quartz fibre filters. PM10 mass concentrations were determined gravimetrically. Samples were analysed for OC and EC with the thermal/optical transmittance method (TOT) and for PAHs by high-performance liquid chromatography (HPLC) with a fluorescence detector. Measurements showed seasonal and spatial variations of mass concentrations for carbon species and for all of the measured PAHs (Flu, Pyr, Chry, BaA, BbF, BaP, BkF, BghiP and IP) in PM10 at the urban site and rural monitoring site described here. Diagnostic PAH ratios (Flu/(Flu + Pyr), BaA/(BaA + Cry), IP/(IP + BghiP), BaP/BghiP, IP/BghiP and BaP/(BaP + Chry)) make it possible to assess the sources of pollution, and these showed that diesel vehicles accounted for most pollution at the rural-industrial (RI) site in the summer, whereas coal and wood combustion were the causes of winter pollution. This difference between winter and summer PAH ratios were more expressed at the RI site than at the UB site because at the UB site the predominant heating fuel was gas. The OC/EC ratio yielded the same conclusion. Factor analysis showed that EC and OC originated from traffic at both sites, PAHs with 5 or more benzene rings originated from wood pellets industry or biomass burning, while Pyr and Flu originated from diesel combustion or as a consequence of different atmospheric behaviour - evaporation and participation in oxidation and photo oxidation processes.

  16. Fullerenic particles for the growth of carbon nanowall-like flowers on multilayer graphene

    Science.gov (United States)

    Guermoune, Abdeladim; Hilke, Michael

    2016-04-01

    Carbon nanowalls (CNWs) are composed of stacks of planar graphene layers with open edges that grow almost vertically on a substrate. Their morphology makes them a promising material for field emission, batteries, light absorbers and enhanced detectors for electrochemical and gas sensors. However, three main challenges prevent the fast development of CNWs: the synthesis is energetically demanding, poorly transferable to suitable substrates, and the growth mechanism is not understood. Here, we present a simple method to grow carbon nanowall-like flowers on multilayer graphene through fullerenic particles using thermal CVD and copper. The hydrophobicity of the fabricated hybrid material facilitates its transfer to any substrate. Our findings can boost the understanding of the physical properties and the practical applicability of CNWs. At the same time, our work is a concrete example of the role of multilayer graphene as a platform to one-step synthesis of new transferable graphenic materials.

  17. Engineering a novel material: Nanometric titanium carbide particles in a matrix of carbon nanotubes

    CERN Document Server

    BADIE, Sylvain

    2015-01-01

    New physics studies at ISOLDE are motivated by new beams available, especially beams of exotic nuclei located at the frontier of the nuclear chart. Such beams are often short lived (in the order of milliseconds) and decay before they can be extracted from the target material, where typical diffusion times are in the order of seconds or more. Novel nanostructured and nanocomposite target materials have been developed to increase the release efficiency by reducing the diffusion paths and so the diffusion times, allowing ISOLDE to deliver new and more intense beams of exotic nuclei. 35Ca (25 ms half-life) was attempted by developing a titanium carbide and carbon black nanocomposite, but such isotope could not be extracted. A different production method with different precursors - titanium oxide and multiwall carbon nanotubes - is here proposed and expected to yield a target material which will increase the release rates of such isotope. A novel material, very porous, consisting of titanium carbide particles disp...

  18. Theoretical analysis of the interfacial phenomena during the injection of carbon particles into EAF slags

    Energy Technology Data Exchange (ETDEWEB)

    Rodriguez, H.H.; Morales, R.D. [Instituto Politecnico Nacional, Mexico City (Mexico). Dept. of Metallurgy and Materials Engineering; Conejo, A.N. [Inst. Tecnologico de Morelia (Mexico)

    2001-08-01

    A theoretical analysis of FeO reduction through the injection of carbon fines in electric arc furnace slags, involving the interfacial phenomena at the liquid-gas-solid interface, has been performed using basic principles of transport phenomena and physical chemistry of steelmaking. It was found that small angle contacts between slag and carbon favour FeO reduction. Moreover, FeO in basic slags are more prone to be reduced because the interfacial liquid-gas interface has more free reaction places. In acid slags FeO reduction is difficult because the gas-liquid interface is partially filled by polymeric silicates. When the particle size is smaller than 100 {mu}m the influence of slag basicity is considerably decreased. Practical applications of these results can be found in electric arc furnace shops aiming at the mastering of slag foaming practices and energy saving. (orig.)

  19. Amelioration of Experimental Autoimmune Encephalomyelitis by Plumbagin through Down-Regulation of JAK-STAT and NF-κB Signaling Pathways

    OpenAIRE

    Yan Jia; Ji Jing; Yang Bai; Zhen Li; Lande Liu; Jian Luo; Mingyao Liu; Huaqing Chen

    2011-01-01

    Plumbagin (PL), a herbal compound derived from roots of the medicinal plant Plumbago zeylanica, has been shown to have immunosuppressive properties. Present report describes that PL is a potent novel agent in control of encephalitogenic T cell responses and amelioration of mouse experimental autoimmune encephalomyelitis (EAE), through down-regulation of JAK-STAT pathway. PL was found to selectively inhibit IFN-γ and IL-17 production by CD4(+) T cells, which was mediated through abrogated phos...

  20. DNA methylation-mediated down-regulation of DNA methyltransferase-1 (DNMT1) is coincident with, but not essential for, global hypomethylation in human placenta.

    Science.gov (United States)

    Novakovic, Boris; Wong, Nick C; Sibson, Mandy; Ng, Hong-Kiat; Morley, Ruth; Manuelpillai, Ursula; Down, Thomas; Rakyan, Vardhman K; Beck, Stephan; Hiendleder, Stefan; Roberts, Claire T; Craig, Jeffrey M; Saffery, Richard

    2010-03-26

    The genome of extraembryonic tissue, such as the placenta, is hypomethylated relative to that in somatic tissues. However, the origin and role of this hypomethylation remains unclear. The DNA methyltransferases DNMT1, -3A, and -3B are the primary mediators of the establishment and maintenance of DNA methylation in mammals. In this study, we investigated promoter methylation-mediated epigenetic down-regulation of DNMT genes as a potential regulator of global methylation levels in placental tissue. Although DNMT3A and -3B promoters lack methylation in all somatic and extraembryonic tissues tested, we found specific hypermethylation of the maintenance DNA methyltransferase (DNMT1) gene and found hypomethylation of the DNMT3L gene in full term and first trimester placental tissues. Bisulfite DNA sequencing revealed monoallelic methylation of DNMT1, with no evidence of imprinting (parent of origin effect). In vitro reporter experiments confirmed that DNMT1 promoter methylation attenuates transcriptional activity in trophoblast cells. However, global hypomethylation in the absence of DNMT1 down-regulation is apparent in non-primate placentas and in vitro derived human cytotrophoblast stem cells, suggesting that DNMT1 down-regulation is not an absolute requirement for genomic hypomethylation in all instances. These data represent the first demonstration of methylation-mediated regulation of the DNMT1 gene in any system and demonstrate that the unique epigenome of the human placenta includes down-regulation of DNMT1 with concomitant hypomethylation of the DNMT3L gene. This strongly implicates epigenetic regulation of the DNMT gene family in the establishment of the unique epigenetic profile of extraembryonic tissue in humans.

  1. Maternal Protein Restriction in the Rat Inhibits Placental Insulin, mTOR, and STAT3 Signaling and Down-Regulates Placental Amino Acid Transporters

    OpenAIRE

    Rosario, Fredrick J.; Jansson, Nina; Kanai, Yoshikatsu; Prasad, Puttur D; Powell, Theresa L.; Jansson, Thomas

    2011-01-01

    The mechanisms underlying reduced fetal growth in response to maternal protein restriction are not well established. Maternal levels of insulin, IGF-I, and leptin are decreased in rats fed a low protein (LP) diet. Because these hormones stimulate placental amino acid transporters in vitro, we hypothesized that maternal protein restriction inhibits placental leptin, insulin/IGF-I, and mammalian target of rapamycin signaling and down-regulates the expression and activity of placental amino acid...

  2. Wnt-activation down-regulates Olfactomedin-1 (Olfm-1) in Fallopian tubal Epithelial cells: A Microenvironment Predisposed to Tubal Ectopic Pregnancy

    OpenAIRE

    Kodithuwakku, Suranga P; Pang, Ronald T. K.; Ernest H Y Ng; Cheung, Annie N. Y.; Horne, Andrew W.; Ho, Pak-Chung; Yeung, William S. B.; Lee, Kai-Fai

    2011-01-01

    Ectopic pregnancy occurs when the embryo failed to transits to the uterus and attached to the luminal epithelium of Fallopian tube. Tubal ectopic pregnancy (EP) is a common gynecological emergency and more than 95% of EP occurs in the ampullary region of the Fallopian tube (FT). In humans, Wnt-activation and down-regulation of Olfactomedin-1 (Olfm-1) occur in the receptive endometrium and coincided with embryo implantation in vivo. Whether similar molecular changes happen in the Fallopian tub...

  3. Growth Hormone-induced JAK2 Signaling and GH Receptor Down-regulation: Role of GH Receptor Intracellular Domain Tyrosine Residues

    OpenAIRE

    Deng, Luqin; Jiang, Jing; Frank, Stuart J.

    2012-01-01

    GH receptor (GHR) mediates important somatogenic and metabolic effects of GH. A thorough understanding of GH action requires intimate knowledge of GHR activation mechanisms, as well as determinants of GH-induced receptor down-regulation. We previously demonstrated that a GHR mutant in which all intracellular tyrosine residues were changed to phenylalanine was defective in its ability to activate signal transducer and activator of transcription (STAT)5 and deficient in GH-induced down-regulati...

  4. Involvement of tyrosine residues located in the carboxyl tail of the human beta 2-adrenergic receptor in agonist-induced down-regulation of the receptor.

    OpenAIRE

    Valiquette, M; Bonin, H.; Hnatowich, M; Caron, M G; Lefkowitz, R J; Bouvier, M

    1990-01-01

    Chronic exposure of various cell types to adrenergic agonists leads to a decrease in cell surface beta 2-adrenergic receptor (beta 2AR) number. Sequestration of the receptor away from the cell surface as well as a down-regulation of the total number of cellular receptors are believed to contribute to this agonist-mediated regulation of receptor number. However, the molecular mechanisms underlying these phenomena are not well characterized. Recently, tyrosine residues located in the cytoplasmi...

  5. Down-Regulation of EBV-LMP1 Radio-Sensitizes Nasal Pharyngeal Carcinoma Cells via NF-κB Regulated ATM Expression

    OpenAIRE

    Xiaoqian Ma; Lifang Yang; Lanbo Xiao; Min Tang; Liyu Liu; Zijian Li; Mengyao Deng; Lunquan Sun; Ya Cao

    2011-01-01

    BACKGROUND: The latent membrane protein 1 (LMP1) encoded by EBV is expressed in the majority of EBV-associated human malignancies and has been suggested to be one of the major oncogenic factors in EBV-mediated carcinogenesis. In previous studies we experimentally demonstrated that down-regulation of LMP1 expression by DNAzymes could increase radiosensitivity both in cells and in a xenograft NPC model in mice. RESULTS: In this study we explored the molecular mechanisms underlying the radiosens...

  6. Resveratrol and clofarabine induces a preferential apoptosis-activating effect on malignant mesothelioma cells by Mcl-1 down-regulation and caspase-3 activation

    OpenAIRE

    Lee, Yoon-Jin; Lee, Yong-Jin; LEE, SANG-HAN

    2015-01-01

    We previously demonstrated that resveratrol and clofarabine elicited a marked cytotoxicity on malignant mesothelioma (MM) MSTO-211H cells but not on the corresponding normal mesothelial MeT-5A cells. Little is known of the possible molecules that could be used to predict preferential chemosensitivity on MSTO-211H cells. Resveratrol and clofarabine induced down-regulation of Mcl-1 protein level in MSTO-211H cells. Treatment of cells with cycloheximide in the presence of proteasome inhibitor MG...

  7. Src family kinase inhibitor PP2 efficiently inhibits cervical cancer cell proliferation through down-regulating phospho-Src-Y416 and phospho-EGFR-Y1173.

    Science.gov (United States)

    Kong, Lu; Deng, Zhihong; Shen, Haiying; Zhang, Yuxiang

    2011-02-01

    Tyrosine (Y) kinases inhibitors have been approved for targeted treatment of cancer. However, their clinical use is limited to some cancers and the mechanism of their action remains unclear. Previous study has indicated that PP2, a selective inhibitor of the Src family of non-receptor tyrosine kinases (nRTK), efficiently repressed cervical cancer growth in vitro and in vivo. In this regard, our aims are to explore the mechanism of PP2 on cervical cancer cell growth inhibition by investigating the suppressive divergence among PP1, PP2, and a negative control compound PP3. MTT results showed that three compounds had different inhibitory effects on proliferation of two cervical cancer cells, HeLa and SiHa, and PP2 was most efficient in a time- and dose-dependent manner. Moreover, we found 10 μM PP2 down-regulated pSrc-Y416 (P < 0.05), pEGFR-Y845 (P < 0.05), and -Y1173 (P < 0.05) expression levels, while 10 μM PP1 down-regulated pSrc-Y416 (P < 0.05) and pEGFR-Y845 (P < 0.05), but not pEGFR-Y1173; 10 μM PP3 down-regulated only pEGFR-Y1173 (P < 0.05). PP2 could modulate cell cycle arrest by up-regulating p21(Cip1) and p27(Kip1) in both HeLa and SiHa cells and down-regulating expression of cyclin A, and cyclin dependent kinase-2, -4 (Cdk-2, -4) in HeLa and of cyclin B and Cdk-2 in SiHa. Our results indicate that Src pathway and EGFR pathway play different roles in the proliferation of cervical cancer cells and PP2 efficiently reduces cervical cancer cell proliferation by reduction of both Src and EGFR activity.

  8. Francisella tularensis elicits IL-10 via a PGE₂-inducible factor, to drive macrophage MARCH1 expression and class II down-regulation.

    Directory of Open Access Journals (Sweden)

    Danielle Hunt

    Full Text Available Francisella tularensis is a bacterial pathogen that uses host-derived PGE₂ to subvert the host's adaptive immune responses in multiple ways. Francisella-induced PGE₂ acts directly on CD4 T cells to blunt production of IFN-γ. Francisella-induced PGE₂ can also elicit production of a >10 kDa soluble host factor termed FTMØSN (F. tularensismacrophage supernatant, which acts on IFN-γ pre-activated MØ to down-regulate MHC class II expression via a ubiquitin-dependent mechanism, blocking antigen presentation to CD4 T cells. Here, we report that FTMØSN-induced down-regulation of MØ class II is the result of the induction of MARCH1, and that MØ expressing MARCH1 "resistant" class II molecules are resistant to FTMØSN-induced class II down-regulation. Since PGE₂ can induce IL-10 production and IL-10 is the only reported cytokine able to induce MARCH1 expression in monocytes and dendritic cells, these findings suggested that IL-10 is the active factor in FTMØSN. However, use of IL-10 knockout MØ established that IL-10 is not the active factor in FTMØSN, but rather that Francisella-elicited PGE₂ drives production of a >10 kDa host factor distinct from IL-10. This factor then drives MØ IL-10 production to induce MARCH1 expression and the resultant class II down-regulation. Since many human pathogens such as Salmonella typhi, Mycobacterium tuberculosis and Legionella pneumophila also induce production of host PGE₂, these results suggest that a yet-to-be-identified PGE₂-inducible host factor capable of inducing IL-10 is central to the immune evasion mechanisms of multiple important human pathogens.

  9. Down-regulation of OsSPX1 caused semi-male sterility, resulting in reduction of grain yield in rice.

    Science.gov (United States)

    Zhang, Kang; Song, Qian; Wei, Qiang; Wang, Chunchao; Zhang, Liwei; Xu, Wenying; Su, Zhen

    2016-08-01

    OsSPX1, a rice SPX domain gene, involved in the phosphate (Pi)-sensing mechanism plays an essential role in the Pi-signalling network through interaction with OsPHR2. In this study, we focused on the potential function of OsSPX1 during rice reproductive phase. Based on investigation of OsSPX1 antisense and sense transgenic rice lines in the paddy fields, we discovered that the down-regulation of OsSPX1 caused reduction of seed-setting rate and filled grain number. Through examination of anthers and pollens of the transgenic and wild-type plants by microscopy, we found that the antisense of OsSPX1 gene led to semi-male sterility, with lacking of mature pollen grains and phenotypes with a disordered surface of anthers and pollens. We further conducted rice whole-genome GeneChip analysis to elucidate the possible molecular mechanism underlying why the down-regulation of OsSPX1 caused deficiencies in anthers and pollens and lower seed-setting rate in rice. The down-regulation of OsSPX1 significantly affected expression of genes involved in carbohydrate metabolism and sugar transport, anther development, cell cycle, etc. These genes may be related to pollen fertility and male gametophyte development. Our study demonstrated that down-regulation of OsSPX1 disrupted rice normal anther and pollen development by affecting carbohydrate metabolism and sugar transport, leading to semi-male sterility, and ultimately resulted in low seed-setting rate and grain yield. PMID:26806409

  10. Black carbon absorption at the global scale is affected by particle-scale diversity in composition

    Science.gov (United States)

    Fierce, Laura; Bond, Tami C.; Bauer, Susanne E.; Mena, Francisco; Riemer, Nicole

    2016-09-01

    Atmospheric black carbon (BC) exerts a strong, but uncertain, warming effect on the climate. BC that is coated with non-absorbing material absorbs more strongly than the same amount of BC in an uncoated particle, but the magnitude of this absorption enhancement (Eabs) is not well constrained. Modelling studies and laboratory measurements have found stronger absorption enhancement than has been observed in the atmosphere. Here, using a particle-resolved aerosol model to simulate diverse BC populations, we show that absorption is overestimated by as much as a factor of two if diversity is neglected and population-averaged composition is assumed across all BC-containing particles. If, instead, composition diversity is resolved, we find Eabs=1-1.5 at low relative humidity, consistent with ambient observations. This study offers not only an explanation for the discrepancy between modelled and observed absorption enhancement, but also demonstrates how particle-scale simulations can be used to develop relationships for global-scale models.

  11. Charged particle's flux measurement from PMMA irradiated by 80 MeV/u carbon ion beam

    CERN Document Server

    Agodi, C; Bellini, F; Cirrone, G A P; Collamati, F; Cuttone, G; De Lucia, E; De Napoli, M; Di Domenico, A; Faccini, R; Ferroni, F; Fiore, S; Gauzzi, P; Iarocci, E; Marafini, M; Mattei, I; Muraro, S; Paoloni, A; Patera, V; Piersanti, L; Romano, F; Sarti, A; Sciubba, A; Vitale, E; Voena, C

    2012-01-01

    Hadrontherapy is an emerging technique in cancer therapy that uses beams of charged particles. To meet the improved capability of hadrontherapy in matching the dose release with the cancer position, new dose monitoring techniques need to be developed and introduced into clinical use. The measurement of the fluxes of the secondary particles produced by the hadron beam is of fundamental importance in the design of any dose monitoring device and is eagerly needed to tune Monte Carlo simulations. We report the measurements done with charged secondary particles produced from the interaction of a 80 MeV/u fully stripped carbon ion beam at the INFN Laboratori Nazionali del Sud, Catania, with a Poly-methyl methacrylate target. Charged secondary particles, produced at 90$\\degree$ with respect to the beam axis, have been tracked with a drift chamber, while their energy and time of flight has been measured by means of a LYSO scintillator. Secondary protons have been identified exploiting the energy and time of flight in...

  12. Photocurrent spectroscopy of exciton and free particle optical transitions in suspended carbon nanotube pn-junctions

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Shun-Wen [Department of Physics and Astronomy, University of Southern California, Los Angeles, California 90089 (United States); Theiss, Jesse; Hazra, Jubin; Aykol, Mehmet; Kapadia, Rehan [Department of Electrical Engineering, University of Southern California, Los Angeles, California 90089 (United States); Cronin, Stephen B. [Department of Physics and Astronomy, University of Southern California, Los Angeles, California 90089 (United States); Department of Electrical Engineering, University of Southern California, Los Angeles, California 90089 (United States); Department of Chemistry, University of Southern California, Los Angeles, California 90089 (United States)

    2015-08-03

    We study photocurrent generation in individual, suspended carbon nanotube pn-junction diodes formed by electrostatic doping using two gate electrodes. Photocurrent spectra collected under various electrostatic doping concentrations reveal distinctive behaviors for free particle optical transitions and excitonic transitions. In particular, the photocurrent generated by excitonic transitions exhibits a strong gate doping dependence, while that of the free particle transitions is gate independent. Here, the built-in potential of the pn-junction is required to separate the strongly bound electron-hole pairs of the excitons, while free particle excitations do not require this field-assisted charge separation. We observe a sharp, well defined E{sub 11} free particle interband transition in contrast with previous photocurrent studies. Several steps are taken to ensure that the active charge separating region of these pn-junctions is suspended off the substrate in a suspended region that is substantially longer than the exciton diffusion length and, therefore, the photocurrent does not originate from a Schottky junction. We present a detailed model of the built-in fields in these pn-junctions, which, together with phonon-assistant exciton dissociation, predicts photocurrents on the same order of those observed experimentally.

  13. Three-particle correlation from a Many-Body Perspective: Trions in a Carbon Nanotube

    OpenAIRE

    Deilmann, Thorsten; Drüppel, Matthias; Rohlfing, Michael

    2016-01-01

    Trion states of three correlated particles (e.g., two electrons and one hole) are essential to understand the optical spectra of doped or gated nanostructures, like carbon nanotubes or transition-metal dichalcogenides. We develop a theoretical many-body description for such correlated states using an ab-initio approach. It can be regarded as an extension of the widely used $GW$ method and Bethe-Salpeter equation, thus allowing for a direct comparison with excitons. We apply this method to a s...

  14. Enhanced dielectric breakdown performances of propylene carbonate modified by nano-particles under microsecond pulses

    Science.gov (United States)

    Hou, Yanpan; Zhang, Jiande; Zhang, Zicheng

    2016-06-01

    Propylene carbonate shows appealing prospects as an energy storage medium in the compact pulsed power sources because of its large permittivity, high dielectric strength, and broad operating temperature range. In this paper, TiO2 nano-particles coated with γ-aminopropyltriethoxylsilane coupling agent are homogeneously dispersed into propylene carbonate and these nano-fluids (NFs) exhibit substantially larger breakdown voltages than those of pure propylene carbonate. It is proposed that interfaces between nano-fillers and propylene carbonate matrix may provide myriad trap sites for charge carriers. The charge carriers can be easily captured at the interfaces between NFs and the electrode, resulting in an increased barrier height and suppressed charge carriers injection, and in the bulk of NFs, the charge carriers' mean free path can be greatly shortened by the scattering effect. As a result, in order for charge carriers acquiring enough energy to generate a region of low density (the bubble) and initiate breakdown in NFs, much higher applied field is needed.

  15. DUSTER: collection of meteoric CaO and carbon smoke particles in the upper stratosphere .

    Science.gov (United States)

    Della Corte, V.; Rietmeijer, F. J. M.; Rotundi, A.; Ferrari, M.; Palumbo, P.

    Nanometer- to micrometer-size particles present in the upper stratosphere are a mixture of terrestrial and extra-terrestrial origins. They can be extraterrestrial particles condensed after meteor ablation. Meteoric dust in bolides is occasionally deposited into the lower stratosphere around 20 km altitude. Nanometer CaO and pure carbon smoke particles were collected at 38 km altitude in the upper stratosphere in the Arctic during June 2008 using DUSTER (Dust in the Upper Stratosphere Tracking Experiment and Retrieval), a balloon-borne instrument for the non-destructive collection of solid particles between 200 nm to 40 microns. We report the collection of micron sized CaCO_3 (calcite) grains. Their morphologies show evidence of melting and condensation after vaporization suggest at temperatures of approximately 3500 K. The formation environment of the collected grains was probably a dense dust cloud formed by the disintegration of a carbonaceous meteoroid during deceleration in the Earth� atmosphere. For the first time, DUSTER collected meteor ablation products that were presumably associated with the disintegration of a bolide crossing the Earth's atmosphere. The collected mostly CaO and pure carbon nanoparticles from the debris cloud of a fireball, included: 1) intact fragments; 2) quenched melted grains; and 3) vapor phase condensation products. The DUSTER project was funded by the Italian Space Agency (ASI), PRIN2008/MIUR (Ministero dell'Istruzione dell'Universitá e della Ricerca), PNRA 2013(Piano Nazionale Ricerca Antartide). CNES graciously provided this flight opportunity. We thank E. Zona and S. Inarta at the Laboratorio di Fisica Cosmica INAF, Osservatorio Astronomico di Capodimonte-Universitá di Napoli Parthenope. F.J.M.R. was supported by grant NNX07AI39G from the NASA Cosmochemistry Program. We thank three anonymous reviewers who assisted us in introducing our new instrument.

  16. Ice nucleating particles from biomass combustion: emission rates and the role of refractory black carbon

    Science.gov (United States)

    Levin, E. J.; McMeeking, G. R.; McCluskey, C. S.; Carrico, C. M.; Nakao, S.; Stockwell, C.; Yokelson, R. J.; Sullivan, R. C.; DeMott, P. J.; Kreidenweis, S. M.

    2015-12-01

    Ice nucleating particles (INPs) allow initial ice crystal formation in clouds at temperatures warmer than about -36 °C and are thus important for cloud and precipitation development. One potential source of INPs to the atmosphere is biomass combustion, such as wildfires, prescribed burning and agricultural burning, which emits large quantities of particulate matter into the atmosphere and is a major source of black carbon (BC) aerosol. To better understand and constrain INP emissions from biomass combustion, globally relevant fuels were used in a series of burns during a study called FLAME 4 at the USFS Fire Sciences Laboratory in Missoula, MT. Concentrations of immersion mode INPs were measured using a Colorado State University Continuous Flow Diffusion Chamber (CFDC). During the first part of the study, emissions were measured in real time as fires progressed from ignition to flaming and smoldering phases. INP emissions were observed predominately during periods of intensely flaming combustion. Roughly 75% of measured burns produced detectable INP concentrations and these had, on average, higher combustion efficiencies and higher BC emissions. During the second half of FLAME 4, we directly measured the contribution of refractory black carbon (rBC) to INP concentrations by selectively removing these particles via laser-induced incandescence (LII) using a Single Particle Soot Photometer (SP2; Droplet Measurement Technologies). The SP2 uses a 1064 nm Na:YAG laser to heat rBC aerosol to their vaporization temperatures, thus removing them from the sampled aerosol. By passing combustion aerosol through the SP2 with the laser on and off while measuring the remaining aerosol with the CFDC, we were able to determine the contribution of rBC to the INP population. Reductions in INPs of 0 - 70% were observed when removing rBC from the combustion aerosol, indicating the importance of rBC particles to INP concentrations for some burn scenarios.

  17. Real-time neurofeedback using functional MRI could improve down-regulation of amygdala activity during emotional stimulation: a proof-of-concept study.

    Science.gov (United States)

    Brühl, Annette Beatrix; Scherpiet, Sigrid; Sulzer, James; Stämpfli, Philipp; Seifritz, Erich; Herwig, Uwe

    2014-01-01

    The amygdala is a central target of emotion regulation. It is overactive and dysregulated in affective and anxiety disorders and amygdala activity normalizes with successful therapy of the symptoms. However, a considerable percentage of patients do not reach remission within acceptable duration of treatment. The amygdala could therefore represent a promising target for real-time functional magnetic resonance imaging (rtfMRI) neurofeedback. rtfMRI neurofeedback directly improves the voluntary regulation of localized brain activity. At present, most rtfMRI neurofeedback studies have trained participants to increase activity of a target, i.e. up-regulation. However, in the case of the amygdala, down-regulation is supposedly more clinically relevant. Therefore, we developed a task that trained participants to down-regulate activity of the right amygdala while being confronted with amygdala stimulation, i.e. negative emotional faces. The activity in the functionally-defined region was used as online visual feedback in six healthy subjects instructed to minimize this signal using reality checking as emotion regulation strategy. Over a period of four training sessions, participants significantly increased down-regulation of the right amygdala compared to a passive viewing condition to control for habilitation effects. This result supports the concept of using rtfMRI neurofeedback training to control brain activity during relevant stimulation, specifically in the case of emotion, and has implications towards clinical treatment of emotional disorders.

  18. Down-regulation of the P-glycoprotein relevant for multidrug resistance by intracellular acidification through the crosstalk of MAPK signaling pathways.

    Science.gov (United States)

    Jin, Weina; Lu, Ying; Li, Qinghua; Wang, Jian; Zhang, Hongju; Chang, Guoqiang; Lin, Yani; Pang, Tianxiang

    2014-09-01

    In our previous study, we have found that the tumor multidrug resistance mediated by P-glycoprotein could be reversed by sustained intracellular acidification through down-regulating the multidrug resistance gene 1 mRNA and P-glycoprotein expression. However, the molecular events linking the intracellular acidification and the regulation of P-glycoprotein remain unclear. In the present study, the molecular pathways involved in the regulation of P-glycoprotein expression by the intracellular acidification were investigated. We found that the P-glycoprotein expression was down-regulated by the intracellular acidification through inhibition of p38 mitogen-activated protein kinase (MAPK) and the activation of c-Jun N-terminal kinase (JNK) in the resisitant K562/DOX cells. In the sensitive K562 and HL60 cell lines, the changes of the p38 MAPK expression after the acidification are not as obvious as that of K562/DOX cells, but the activation of extracellular signal-regulated kinase (ERK) is also observed, which indicates that the down-regulation of p38 MAPK by the intracellular acidification might be the resistant cell line specific. Blockade of ERK and JNK signaling by the inhibitors or RNA interference increased p38MAPK activities suggesting that cross-talk within MAPKs is also important for this response. Our study provides the first direct evidence that the reversal of P-glycoprotein-mediated multidrug resistance by intracellular acidification is mediated by the crosstalk of MAPK signaling pathways.

  19. Growth promotion in pigs by oxytetracycline coincides with down regulation of serum inflammatory parameters and of hibernation-associated protein HP-27.

    Science.gov (United States)

    Soler, Laura; Miller, Ingrid; Hummel, Karin; Razzazi-Fazeli, Ebrahim; Jessen, Flemming; Escribano, Damian; Niewold, Theo

    2016-05-01

    The growth promoting effect of supplementing animal feed with antibiotics like tetracycline has traditionally been attributed to their antibiotic character. However, more evidence has been accumulated on their direct anti-inflammatory effect during the last two decades. Here we used a pig model to explore the systemic molecular effect of feed supplementation with sub therapeutic levels of oxytetracycline (OTC) by analysis of serum proteome changes. Results showed that OTC promoted growth, coinciding with a significant down regulation of different serum proteins related to inflammation, oxidation and lipid metabolism, confirming the anti-inflammatory mechanism of OTC. Interestingly, apart from the classic acute phase reactants also down regulation was seen of a hibernation associated plasma protein (HP-27), which is to our knowledge the first description in pigs. Although the exact function in non-hibernators is unclear, down regulation of HP-27 could be consistent with increased appetite, which is possibly linked to the anti-inflammatory action of OTC. Given that pigs are good models for human medicine due to their genetic and physiologic resemblance, the present results might also be used for rational intervention in human diseases in which inflammation plays an important role such as obesity, type 2 diabetes and cardiovascular diseases. PMID:26914286

  20. Mesenchymal stem cells cultured under hypoxia escape from senescence via down-regulation of p16 and extracellular signal regulated kinase

    International Nuclear Information System (INIS)

    Hypoxia has been considered to affect the properties of tissue stem cells including mesenchymal stem cells (MSCs). Effects of long periods of exposure to hypoxia on human MSCs, however, have not been clearly demonstrated. MSCs cultured under normoxic conditions (20% pO2) ceased to proliferate after 15-25 population doublings, while MSCs cultured under hypoxic conditions (1% pO2) retained the ability to proliferate with an additional 8-20 population doublings. Most of the MSCs cultured under normoxic conditions were in a senescent state after 100 days, while few senescent cells were found in the hypoxic culture, which was associated with a down-regulation of p16 gene expression. MSCs cultured for 100 days under hypoxic conditions were superior to those cultured under normoxic conditions in the ability to differentiate into the chondro- and adipogenic, but not osteogenic, lineage. Among the molecules related to mitogen-activated protein kinase (MAPK) signaling pathways, extracellular signal regulated kinase (ERK) was significantly down-regulated by hypoxia, which helped to inhibit the up-regulation of p16 gene expression. Therefore, the hypoxic culture retained MSCs in an undifferentiated and senescence-free state through the down-regulation of p16 and ERK.

  1. Down-regulation of MTA1 protein leads to the inhibition of migration, invasion, and angiogenesis of non-small-cell lung cancer cell line

    Institute of Scientific and Technical Information of China (English)

    Shuhai Li; Hui Tian; Weiming Yue; Lin Li; Cun Gao; Libo Si; Wenjun Li

    2013-01-01

    Metastasis-associated protein 1 (MTA1) high expression has been detected in a wide variety of human aggressive tumors and plays important roles in the malignant biological behaviors such as invasion,metastasis,and angiogenesis.However,the specific roles and mechanisms of MTA1 protein in regulating the malignant behaviors of non-small-cell lung cancer (NSCLC) cells still remain unclear.To elucidate the detailed functions of MTA1 protein,we down-regulated the MTA1 protein expression in NSCLC cell line by RNA interference (RNAi) in vitro,and found that down-regulation of MTA1 protein significantly inhibited the migration and invasion potentials of 95D cells.Further research revealed that down-reguiation of MTA1 protein significantly decreased the activity of matrix metalloproteinase-9,which could be the mechanism responsible for the inhibition of 95D cells migration and invasion.In addition,the tube formation assay demonstrated that the number of complete tubes induced by the conditioned medium of MTA1-siRNA 95D cells was significantly smaller than that of 95D cells.These findings demonstrate that MTA1 protein plays important roles in regulating the migration,invasion,and angiogenesis potentials of 95D cells,suggesting that MTA1 protein down-regulation by RNAi might be a novel therapeutic approach to inhibit the progression of NSCLC.

  2. Homologous down-regulation of the insulin receptor is associated with increased receptor biosynthesis in cultured human lymphocytes (IM-9 line)

    International Nuclear Information System (INIS)

    Cultured IM-9 lymphocytes were preincubated with 1 μM insulin, a condition resulting in a 56% reduction in cell surface insulin receptors. Cellular proteins were then metabolically labeled, and the radioactivity incorporated into the insulin proreceptor and receptor mature subunits was measured over a 4-hr chase period. As early as 30 min of chase, incorporation into the proreceptor was 28 +/- 6% higher in down-regulated cells than in control cells. By 1 hr of chase, the difference reached 41 +/- 14% for the proreceptor and 84 +/- 28% for the α subunit, values returned to normal by 2 hr. At 4 hr of chase, labeling of the α subunit of down-regulated cells was diminished 36 +/- 9% below control. The increased biosynthetic rate of the proreceptor was more prominent when the chase medium contained 25 μM monensin, an inhibitor of processing of the proreceptor into mature subunits. Similar effects occurred whether [3H]mannose or [3H]lysine was used as biosynthetic marker. The effect was specific for the insulin receptor. These data demonstrate that insulin receptor homologous down-regulation is associated with increased proreceptor biosynthesis and processing into mature subunits. This might represent a cellular mechanism compensating for insulin-induced receptor loss

  3. Warfarin and coumarin-like Murraya paniculata extract down-regulate EpCAM-mediated cell adhesion: individual components versus mixture for studying botanical metastatic chemopreventives.

    Science.gov (United States)

    Shao, Jingwei; Zhou, Suxia; Jiang, Zhou; Chi, Ting; Ma, Ji; Kuo, Minliang; Lee, Alan Yueh-Luen; Jia, Lee

    2016-01-01

    We recently defined cancer metastatic chemoprevention as utilizing safe and effective molecules to comprehensively prevent the spark of activation-adhesion-extravasation-proliferation metastatic cascade caused by circulating tumor cells (CTCs). The strategy focuses on preventing the most important starting point of the cascade. We identified an extract from a well-known medical plant Murraya paniculata, which inhibited both embryonic implantation to human endometrium as traditionally-used for abortion and CTC adhesion to human endothelium. Here, we separated and characterized five coumarin-containing components (Z1-Z5) from the botanic extract. Flow cytometry revealed that within 1-100 μg/mL, Z3 and Z5 down-regulated EpCAM expression in human colon HCT116, whereas, Z1 and Z2 did oppositely. Warfarin and Z1-Z5 component mixture (CM) also down-regulated EpCAM expression. The down-regulation of EpCAM by Z3, Z5, CM and warfarin was confirmed by western blotting, and caused inhibition on adhesion of cancer cells to human endothelial cells. Rat coagulation study showed that warfarin prolonged prothrombin time, whereas, Z3 did not. The present studies revealed that, for the first time, warfarin and coumarin-like components Z3, Z5 and CM from Murraya paniculata could directly inhibit EpCAM-mediated cell-cell adhesion. PMID:27480614

  4. Allicin inhibits SDF-1alpha-induced T cell interactions with fibronectin and endothelial cells by down-regulating cytoskeleton rearrangement, Pyk-2 phosphorylation and VLA-4 expression.

    Science.gov (United States)

    Sela, Uri; Ganor, Sharon; Hecht, Iris; Brill, Alexander; Miron, Talia; Rabinkov, Aharon; Wilchek, Meir; Mirelman, David; Lider, Ofer; Hershkoviz, Rami

    2004-04-01

    Allicin, a major ingredient of fresh garlic extract that is produced during the crushing of garlic cloves, exerts various beneficial biological effects, including a broad spectrum of antimicrobial activity, antihyperlipidaemic and antihypertensive effects. However, how allicin affects the immune system is less well known, and its effect on human T cells has never been studied. Here, we examined the in-vitro effects of allicin on the functioning of T cells related to their entry to inflamed extravascular sites. We found that allicin (20-100 microm) inhibits the SDF-1alpha (CXCL12)-induced T cell migration through fibronectin (FN), and that this inhibition is mediated by the down-regulation of (i) the reorganization of cortical actin and the subsequent T cell polarization, and (ii) T cell adhesion to FN. Moreover, allicin also inhibited T cell adhesion to endothelial cells and transendothelial migration. The mechanisms underlying these inhibitory effects of allicin are associated with its ability to down-regulate the phosphorylation of Pyk2, an intracellular member of the focal adhesion kinases, and to reduce the expression of the VCAM-1- and FN-specific alpha4beta1-integrin (VLA-4). The ability of allicin to down-regulate these chemokine-induced and VLA-4-mediated T cell functions explains its beneficial biological effects in processes where T cells play an important role and suggests that allicin may be used therapeutically with chronic inflammatory diseases. PMID:15056375

  5. Inhibition of CK2α down-regulates Hedgehog/Gli signaling leading to a reduction of a stem-like side population in human lung cancer cells.

    Directory of Open Access Journals (Sweden)

    Shulin Zhang

    Full Text Available Protein kinase CK2 is frequently elevated in a variety of human cancers. The Hedgehog (Hh signaling pathway has been implicated in stem cell maintenance, and its aberrant activation has been indicated in several types of cancer, including lung cancer. In this study, we show that CK2 is positively involved in Hh/Gli signaling in lung cancer cell lines A549 and H1299. First, we found a correlation between CK2α and Gli1 mRNA levels in 100 primary lung cancer tissues. Down-regulation of Gli1 expression and transcriptional activity were demonstrated after the silencing of CK2α in lung cancer cells. In addition, CK2α siRNA down-regulated the expression of Hh target genes. Furthermore, two small-molecule CK2α inhibitors led to a dose-dependent inhibition of Gli1 expression and transcriptional activity in lung cancer cells. Reversely, forced over-expression of CK2α resulted in an increase both in Gli1 expression and transcriptional activity in A549 cells. Finally, the inhibition of Hh/Gli by CK2α siRNA led to a reduction of a cancer stem cell-like side population that shows higher ABCG2 expression level. Thus, we report that the inhibition of CK2α down-regulates Hh/Gli signaling and subsequently reduces stem-like side population in human lung cancer cells.

  6. Carbon-based phytoplankton size classes retrieved via ocean color estimates of the particle size distribution

    Directory of Open Access Journals (Sweden)

    T. S. Kostadinov

    2015-05-01

    Full Text Available Owing to their important roles in biogeochemical cycles, phytoplankton functional types (PFTs have been the aim of an increasing number of ocean color algorithms. Yet, none of the existing methods are based on phytoplankton carbon (C biomass, which is a fundamental biogeochemical and ecological variable and the "unit of accounting" in Earth System models. We present a novel bio-optical algorithm to retrieve size-partitioned phytoplankton carbon from ocean color satellite data. The algorithm is based on existing algorithms to estimate particle volume from a power-law particle size distribution (PSD. Volume is converted to carbon concentrations using a compilation of allometric relationships. We quantify absolute and fractional biomass in three PFTs based on size – picophytoplankton (0.5–2 μm in diameter, nanophytoplankton (2–20 μm and microphytoplankton (20–50 μm. The mean spatial distributions of total phytoplankton C biomass and individual PFTs, derived from global SeaWiFS monthly ocean color data, are consistent with current understanding of oceanic ecosystems, i.e. oligotrophic regions are characterized by low biomass and dominance of picoplankton, whereas eutrophic regions have large biomass to which nanoplankton and microplankton contribute relatively larger fractions. Global spatially integrated phytoplankton carbon biomass standing stock estimates using our PSD-based approach yield on average ~0.2–0.3 Gt of C, consistent with analogous estimates from two other ocean color algorithms, and several state-of-the-art Earth System models. However, the range of phytoplankton C biomass spatial variability globally is larger than estimated by any other models considered here, because the PSD-based algorithm is not a priori empirically constrained and introduces improvement over the assumptions of the other approaches. Satisfactory in situ closure observed between PSD and POC measurements lends support to the theoretical basis of the

  7. Dose-dependent regulation of microbial activity on sinking particles by polyunsaturated aldehydes: Implications for the carbon cycle

    Science.gov (United States)

    Edwards, Bethanie R.; Bidle, Kay D.; Van Mooy, Benjamin A. S.

    2015-05-01

    Diatoms and other phytoplankton play a crucial role in the global carbon cycle, fixing CO2 into organic carbon, which may then be exported to depth via sinking particles. The molecular diversity of this organic carbon is vast and many highly bioactive molecules have been identified. Polyunsaturated aldehydes (PUAs) are bioactive on various levels of the marine food web, and yet the potential for these molecules to affect the fate of organic carbon produced by diatoms remains an open question. In this study, the effects of PUAs on the natural microbial assemblages associated with sinking particles were investigated. Sinking particles were collected from 150 m in the water column and exposed to varying concentrations of PUAs in dark incubations over 24 h. PUA doses ranging from 1 to 10 µM stimulated respiration, organic matter hydrolysis, and cell growth by bacteria associated with sinking particles. PUA dosages near 100 µM appeared to be toxic, resulting in decreased bacterial cell abundance and metabolism, as well as pronounced shifts in bacterial community composition. Sinking particles were hot spots for PUA production that contained concentrations within the stimulatory micromolar range in contrast to previously reported picomolar concentrations of these compounds in bulk seawater. This suggests PUAs produced in situ stimulate the remineralization of phytoplankton-derived sinking organic matter, decreasing carbon export efficiency, and shoaling the average depths of nutrient regeneration. Our results are consistent with a "bioactivity hypothesis" for explaining variations in carbon export efficiency in the oceans.

  8. Enhancement of Carbon Nanotube Particle Distribution in PPS/PEEK/Carbon Nanotube Ternary Composites with Sausage-Like Structure

    Directory of Open Access Journals (Sweden)

    Lin Cao

    2016-02-01

    Full Text Available Carbon nanomaterial particles were selectively distributed in an incompatible and high-melting-temperature polymer blend interface, or in a particular phase, to obtain conductive composites. The composite products revealed poor morphology stability and mechanical performance due to processing several times. Poly(phenylene sulfide (PPS and poly(ether ether ketone (PEEK polymers with large differences of processing temperatures were selected as blend components to obtain a compatible blend. PPS/PEEK/multi-walled carbon nanotube (MWCNT ternary nanocomposites were prepared using a controlled melt blending process. The composite samples with similar sausage-like structures of PEEK, as a dispersed phase, promote MWCNT to maximize concentration distribution in the PPS continuous phase. As a result, the theoretical percolation threshold of the composite reduced to 0.347 wt %. Moreover, the conductivity of the composite remained stable even after processing several times. CNTs revealed a particular effect when distributed selectively in this kind of system: it can enhance the dispersion of phases and also provide conductivity to the blend at small CNT contents, which can provide more useful ideas for the development of high-melting-temperature and antistatic or conductive plastic materials.

  9. Automated Chemical Analysis of Internally Mixed Aerosol Particles Using X-ray Spectromicroscopy at the Carbon K-Edge

    Energy Technology Data Exchange (ETDEWEB)

    Gilles, Mary K; Moffet, R.C.; Henn, T.; Laskin, A.

    2011-01-20

    We have developed an automated data analysis method for atmospheric particles using scanning transmission X-ray microscopy coupled with near edge X-ray fine structure spectroscopy (STXM/NEXAFS). This method is applied to complex internally mixed submicrometer particles containing organic and inorganic material. Several algorithms were developed to exploit NEXAFS spectral features in the energy range from 278 to 320 eV for quantitative mapping of the spatial distribution of elemental carbon, organic carbon, potassium, and noncarbonaceous elements in particles of mixed composition. This energy range encompasses the carbon K-edge and potassium L2 and L3 edges. STXM/NEXAFS maps of different chemical components were complemented with a subsequent analysis using elemental maps obtained by scanning electron microscopy coupled with energy dispersive X-ray analysis (SEM/EDX). We demonstrate the application of the automated mapping algorithms for data analysis and the statistical classification of particles.

  10. Effect of Carbon Ash Content on the Thermal and Combustion Properties of Waste Wood Particle / Recycled Polypropylene Composites

    Directory of Open Access Journals (Sweden)

    Chen Kuo-Wei

    2016-01-01

    Full Text Available This study effect of carbon ash content on the thermal stability and combustion behavior of waste wood particle / recycled polypropylene composites was investigated using TGA, DTG, LOI and cone calorimeter. The TGA shows that, as carbon ash content increases, the thermal stability of composites increases, while the residual weight significantly increases, with the residual weight rate of waste wood particle / recycled polypropylene composites increases from 13.97% to 41.02% at 800 ℃ According to cone calorimeter results, in the 50 kW/M2 thermal flow, when carbon ash adding to 70%, peak heat release rate and total heat release quantity, decreases by 68% and 52%, respectively. The LOI of waste wood particle / recycled polypropylene composites improves by about 34%, Conforming UL-94 flammability standard, V-0 rating. The residual weight rate increases by 202.8%, which the significant role of carbon ash in flame retardant.

  11. Downward particle flux and carbon export in the Beaufort Sea, Arctic Ocean; the Malina experiment

    Science.gov (United States)

    Miquel, J.-C.; Gasser, B.; Martín, J.; Marec, C.; Babin, M.; Fortier, L.; Forest, A.

    2015-01-01

    As part of the international, multidisciplinary project Malina, downward particle fluxes were investigated by means of a drifting multi-sediment trap mooring deployed at three sites in the Canadian Beaufort Sea in late summer 2009. Mooring deployments lasted for 28-50 h and targeted the shelf-break and the slope along the Beaufort-Mackenzie continental margin, as well as the edge between the Mackenzie Shelf and the Amundsen Gulf. Besides analyses of C and N, the collected material was investigated for pigments, phyto- and microzooplankton, faecal pellets and swimmers. The measured fluxes were relatively low, in the range of 11-54 mg m-2 d-1 for the total mass, 1-15 mg C m-2 d-1 for organic carbon and 0.2-2.5 mg N m-2 d-1 for nitrogen. Comparison with a long-term trap dataset from the same sampling area showed that the short-term measurements were at the lower end of the high variability characterizing a rather high flux regime during the study period. The sinking material consisted of aggregates and particles that were characterized by the presence of hetero- and autotrophic microzooplankters and diatoms and by the corresponding pigment signatures. Faecal pellets contribution to sinking carbon flux was important, especially at depth where they represented up to 25% of the total carbon flux. The vertical distribution of different morphotypes of pellets showed a marked pattern with cylindrical faeces (produced by calanoid copepods) present mainly within the euphotic zone, whereas elliptical pellets (produced mainly by smaller copepods) were more abundant at mesopelagic depths. These features, together with the density of matter within the pellets, highlighted the role of the zooplankton community in the transformation of carbon issued from the primary production and the transition of that carbon from the productive surface zone to the Arctic Ocean's interior. Our data indicate that sinking carbon flux in this late summer period is primarily the result of a

  12. Downward particle flux and carbon export in the Beaufort Sea, Arctic Ocean; the role of zooplankton

    Science.gov (United States)

    Miquel, J.-C.; Gasser, B.; Martín, J.; Marec, C.; Babin, M.; Fortier, L.; Forest, A.

    2015-08-01

    As part of the international, multidisciplinary project Malina, downward particle fluxes were investigated by means of a drifting multi-sediment trap mooring deployed at three sites in the Canadian Beaufort Sea in late summer 2009. Mooring deployments lasted between 28 and 50 h and targeted the shelf-break and the slope along the Beaufort-Mackenzie continental margin, as well as the edge between the Mackenzie Shelf and the Amundsen Gulf. Besides analyses of C and N, the collected material was investigated for pigments, phyto- and microzooplankton, faecal pellets and swimmers. The measured fluxes were relatively low, in the range of 11-54 mg m-2 d-1 for the total mass, 1-15 mg C m-2 d-1 for organic carbon and 0.2-2.5 mg N m-2 d-1 for nitrogen. Comparison with a long-term trap data set from the same sampling area showed that the short-term measurements were at the lower end of the high variability characterizing a rather high flux regime during the study period. The sinking material consisted of aggregates and particles that were characterized by the presence of hetero- and autotrophic microzooplankters and diatoms and by the corresponding pigment signatures. Faecal pellets contribution to sinking carbon flux was important, especially at depths below 100 m, where they represented up to 25 % of the total carbon flux. The vertical distribution of different morphotypes of pellets showed a marked pattern with cylindrical faeces (produced by calanoid copepods) present mainly within the euphotic zone, whereas elliptical pellets (produced mainly by smaller copepods) were more abundant at mesopelagic depths. These features, together with the density of matter within the pellets, highlighted the role of the zooplankton community in the transformation of carbon issued from the primary production and the transition of that carbon from the productive surface zone to the Arctic Ocean's interior. Our data indicate that sinking carbon flux in this late summer period is primarily

  13. Ambient black carbon particle hygroscopic properties controlled by mixing state and composition

    Directory of Open Access Journals (Sweden)

    D. Liu

    2012-11-01

    Full Text Available The wet removal of black carbon aerosol (BC in the atmosphere is a crucial factor in determining its atmospheric lifetime and thereby the vertical and horizontal distributions, dispersion on local and regional scales, and the direct, semi-direct and indirect radiative forcing effects. The in-cloud scavenging and wet deposition rate of freshly emitted hydrophobic BC will be increased on acquisition of more-hydrophilic components by coagulation or coating processes. The lifetime of BC is still subject to considerable uncertainty for most of the model inputs, which is largely due to the insufficient constraints on the BC hydrophobic-to-hydrophilic conversion process from observational field data. This study was conducted at a site along UK North Norfolk coastline, where the BC particles were transported from different regions within Western Europe. A hygroscopicity tandem differential mobility analyser (HTDMA was coupled with a single particle soot photometer (SP2 to measure the hygroscopic properties of BC particles and associated mixing state in real time. In addition, a Soot Particle AMS (SP-AMS measured the chemical compositions of additional material associated with BC particles. The ensemble of BC particles persistently contained a less-hygroscopic mode at a growth factor (gf of around 1.05 at 90% RH (dry diameter 163 nm. Importantly, a more-hygroscopic mode of BC particles was observed throughout the experiment, the gf of these BC particles extended up to ~1.4–1.6 with the minimum between this and the less hygroscopic mode at a gf ~1.25, or equivalent effective hygroscopicity parameter κ = ~0.1. The gf of BC particles (gfBC was highly influenced by the composition of associated soluble material: increases of gfBC were associated with secondary inorganic components, and these increases were more pronounced when ammonium nitrate was in the BC particles; however the presence of secondary organic matter suppressed the gf

  14. Effect of the particle shape on the optical properties of black carbon aggregates

    Science.gov (United States)

    Skorupski, Krzysztof

    2016-04-01

    Small particles tend to connect to each other and create large geometries, namely aggregates. To simplify the light scattering simulation process, they are usually modelled as assemblies of spheres positioned in point contact. This is a rough approximation because connections between them always exist. In this work we present answers to the three following questions: which optical properties of fractal-like aggregates are strongly dependent on the particle shape, what is the magnitude of the relative extinction error σCext when non-spherical particles are modelled as spheres and whether the relative extinction error σCext is dependent on the aggregate size Np. The paper was aimed at tropospheric black carbon particles and their complex refractive index m was based on the work by Chang and Charalampopoulos. The incident wavelength λ varied from λ = 300nm to λ = 900nm. For the light scattering simulations the ADDA algorithm was used. The polarizability expression was IGT_SO (approximate Integration of Greens Tensor over the dipole) and each particle, regardless of its shape, was composed of ca. Nd ≍ 1000 volume elements (dipoles). In the study, fractal-like aggregates consisted of up to Np = 300 primary particles with the volume equivalent to the volume of a sphere with the radius rp = 15nm. The fractal dimension was Df = 1:8 and the fractal prefactor was kf = 1:3. Geometries were generated with the tunable CC (Cluster-Cluster) algorithm proposed by Filippov et al. The results show that when the extinction cross section σCext is considered, the changes caused by the particle shape, which are especially visible for longer wavelengths λ cannot be neglected. The most significant difference can be observed for the regular tetrahedron. The relative extinction error σCext diminishes slightly along with the number of primary particles Np. However, even when large fractal-like aggregates are studied, it should not be considered as non-existent. On the contrary

  15. Spectrally resolved efficiencies of carbon monoxide (CO photoproduction in the western Canadian Arctic: particles versus solutes

    Directory of Open Access Journals (Sweden)

    G. Song

    2013-06-01

    Full Text Available Spectrally resolved efficiency (i.e. apparent quantum yield, AQY of carbon monoxide (CO photoproduction is a useful indicator of substrate photoreactivity and a crucial parameter for modeling CO photoproduction rates in the water column. Recent evidence has suggested that CO photoproduction from particles in marine waters is significant compared to the well-known CO production from chromophoric dissolved organic matter (CDOM photodegradation. Although CDOM-based CO AQY spectra have been extensively determined, little is known of this information on the particulate phase. Using water samples collected from the Mackenzie estuary, shelf, and Canada Basin in the southeastern Beaufort Sea, the present study for the first time quantified the AQY spectra of particle-based CO photoproduction and compared them with the concomitantly determined CDOM-based CO AQY spectra. CO AQYs of both particles and CDOM decreased with wavelength but the spectral shape of the particulate AQY was flatter in the visible regime. This feature resulted in a disproportionally higher visible light-driven CO production by particles, thereby increasing the ratio of particle- to CDOM-based CO photoproduction with depth in the euphotic zone. In terms of depth-integrated production in the euphotic zone, CO formation from CDOM was dominated by the ultraviolet (UV, 290–400 nm radiation whereas UV and visible light played roughly equal roles in CO production from particles. Spatially, CO AQY of bulk particulate matter (i.e. the sum of organics and inorganics augmented from the estuary and shelf to the basin while CO AQY of CDOM trended inversely. Water from the deep chlorophyll maximum layer revealed higher CO AQYs than did surface water for both particles and CDOM. CO AQY of bulk particulate matter exceeded that of CDOM on the shelf and in the basin, but the sequence reversed in the estuary. Without consideration of the potential role of metal oxides (e.g. iron oxides in particle

  16. Pioglitazone ameliorates nonalcoholic steatohepatitis by down-regulating hepatic nuclear factor-kappa B and cyclooxygenases-2 expression in rats

    Institute of Scientific and Technical Information of China (English)

    ZHAO Jia-sheng; ZHU Feng-shang; LIU Su; YANG Chang-qing; CHEN Xi-mei

    2012-01-01

    was decreased in the NASHgroup.Real-time PCR and Western blotting revealed mRNA and protein expression of COX-2 were increased in theNASH group compared with the control group (0.57±0.08 vs.2.83±0.24; 0.38±0.03 vs.1.00±0.03,P<0.001 and,P=0.004,respectively).After pioglitazone intervention,all of those parameters markedly improved (P <0.05 or P <0.01 ).Conclusion Down-regulating hepatic NF-κB and COX-2 expression,at least in part,is one of the possible therapeutic mechanisms of pioglitazone in NASH rats.

  17. Involvement of SIRT1 in hypoxic down-regulation of c-Myc and β-catenin and hypoxic preconditioning effect of polyphenols

    Energy Technology Data Exchange (ETDEWEB)

    Hong, Kyung-Soo [Department of Biochemistry, Pusan National University School of Medicine, Yangsan (Korea, Republic of); Research Center for Ischemic Tissue regeneration, Pusan National University School of Medicine, Yangsan (Korea, Republic of); Park, Jun-Ik [Department of Biochemistry, Pusan National University School of Medicine, Yangsan (Korea, Republic of); Kim, Mi-Ju; Kim, Hak-Bong; Lee, Jae-Won [Department of Biochemistry, Pusan National University School of Medicine, Yangsan (Korea, Republic of); Research Center for Ischemic Tissue regeneration, Pusan National University School of Medicine, Yangsan (Korea, Republic of); Dao, Trong Tuan; Oh, Won Keun [BK21 Project Team, College of Pharmacy, Chosun University, Gwangju (Korea, Republic of); Kang, Chi-Dug, E-mail: kcdshbw@pusan.ac.kr [Department of Biochemistry, Pusan National University School of Medicine, Yangsan (Korea, Republic of); Kim, Sun-Hee, E-mail: ksh7738@pusan.ac.kr [Department of Biochemistry, Pusan National University School of Medicine, Yangsan (Korea, Republic of); Research Center for Ischemic Tissue regeneration, Pusan National University School of Medicine, Yangsan (Korea, Republic of)

    2012-03-01

    SIRT1 has been found to function as a Class III deacetylase that affects the acetylation status of histones and other important cellular nonhistone proteins involved in various cellular pathways including stress responses and apoptosis. In this study, we investigated the role of SIRT1 signaling in the hypoxic down-regulations of c-Myc and β-catenin and hypoxic preconditioning effect of the red wine polyphenols such as piceatannol, myricetin, quercetin and resveratrol. We found that the expression of SIRT1 was significantly increased in hypoxia-exposed or hypoxic preconditioned HepG2 cells, which was closely associated with the up-regulation of HIF-1α and down-regulation of c-Myc and β-catenin expression via deacetylation of these proteins. In addition, blockade of SIRT1 activation using siRNA or amurensin G, a new potent SIRT1 inhibitor, abolished hypoxia-induced HIF-1α expression but increased c-Myc and β-catenin expression. SIRT1 was also found to stabilize HIF-1α protein and destabilize c-Myc, β-catenin and PHD2 under hypoxia. We also found that myricetin, quercetin, piceatannol and resveratrol up-regulated HIF-1α and down-regulated c-Myc, PHD2 and β-catenin expressions via SIRT1 activation, in a manner that mimics hypoxic preconditioning. This study provides new insights of the molecular mechanisms of hypoxic preconditioning and suggests that polyphenolic SIRT1 activators could be used to mimic hypoxic/ischemic preconditioning. -- Graphical abstract: Polyphenols mimicked hypoxic preconditioning by up-regulating HIF-1α and SIRT1 and down-regulating c-Myc, PHD2, and β-catenin. HepG2 cells were pretreated with the indicated doses of myricetin (MYR; A), quercetin (QUR; B), or piceatannol (PIC; C) for 4 h and then exposed to hypoxia for 4 h. Levels of HIF-1α, SIRT1, c-Myc, β-catenin, and PHD2 were determined by western blot analysis. The data are representative of three individual experiments. Highlights: ► SIRT1 expression is increased in hypoxia

  18. Involvement of SIRT1 in hypoxic down-regulation of c-Myc and β-catenin and hypoxic preconditioning effect of polyphenols

    International Nuclear Information System (INIS)

    SIRT1 has been found to function as a Class III deacetylase that affects the acetylation status of histones and other important cellular nonhistone proteins involved in various cellular pathways including stress responses and apoptosis. In this study, we investigated the role of SIRT1 signaling in the hypoxic down-regulations of c-Myc and β-catenin and hypoxic preconditioning effect of the red wine polyphenols such as piceatannol, myricetin, quercetin and resveratrol. We found that the expression of SIRT1 was significantly increased in hypoxia-exposed or hypoxic preconditioned HepG2 cells, which was closely associated with the up-regulation of HIF-1α and down-regulation of c-Myc and β-catenin expression via deacetylation of these proteins. In addition, blockade of SIRT1 activation using siRNA or amurensin G, a new potent SIRT1 inhibitor, abolished hypoxia-induced HIF-1α expression but increased c-Myc and β-catenin expression. SIRT1 was also found to stabilize HIF-1α protein and destabilize c-Myc, β-catenin and PHD2 under hypoxia. We also found that myricetin, quercetin, piceatannol and resveratrol up-regulated HIF-1α and down-regulated c-Myc, PHD2 and β-catenin expressions via SIRT1 activation, in a manner that mimics hypoxic preconditioning. This study provides new insights of the molecular mechanisms of hypoxic preconditioning and suggests that polyphenolic SIRT1 activators could be used to mimic hypoxic/ischemic preconditioning. -- Graphical abstract: Polyphenols mimicked hypoxic preconditioning by up-regulating HIF-1α and SIRT1 and down-regulating c-Myc, PHD2, and β-catenin. HepG2 cells were pretreated with the indicated doses of myricetin (MYR; A), quercetin (QUR; B), or piceatannol (PIC; C) for 4 h and then exposed to hypoxia for 4 h. Levels of HIF-1α, SIRT1, c-Myc, β-catenin, and PHD2 were determined by western blot analysis. The data are representative of three individual experiments. Highlights: ► SIRT1 expression is increased in hypoxia

  19. The Carbon Aerosol / Particles Nucleation with a Lidar: Numerical Simulations and Field Studies

    Directory of Open Access Journals (Sweden)

    Miffre Alain

    2016-01-01

    Full Text Available In this contribution, we present the results of two recent papers [1,2] published in Optics Express, dedicated to the development of two new lidar methodologies. In [1], while the carbon aerosol (for example, soot particles is recognized as a major uncertainty on climate and public health, we couple lidar remote sensing with Laser-Induced-Incandescence (LII to allow retrieving the vertical profile of very low thermal radiation emitted by the carbon aerosol, in agreement with Planck’s law, in an urban atmosphere over several hundred meters altitude. In paper [2], awarded as June 2014 OSA Spotlight, we identify the optical requirements ensuring an elastic lidar to be sensitive to new particles formation events (NPF-events in the atmosphere, while, in the literature, all the ingredients initiating nucleation are still being unrevealed [3]. Both papers proceed with the same methodology by identifying the optical requirements from numerical simulation (Planck and Kirchhoff’s laws in [1], Mie and T-matrix numerical codes in [2], then presenting lidar field application case studies. We believe these new lidar methodologies may be useful for climate, geophysical, as well as fundamental purposes.

  20. The Carbon Aerosol / Particles Nucleation with a Lidar: Numerical Simulations and Field Studies

    Science.gov (United States)

    Miffre, Alain; Anselmo, Christophe; Francis, Mirvatte; David, Gregory; Rairoux, Patrick

    2016-06-01

    In this contribution, we present the results of two recent papers [1,2] published in Optics Express, dedicated to the development of two new lidar methodologies. In [1], while the carbon aerosol (for example, soot particles) is recognized as a major uncertainty on climate and public health, we couple lidar remote sensing with Laser-Induced-Incandescence (LII) to allow retrieving the vertical profile of very low thermal radiation emitted by the carbon aerosol, in agreement with Planck's law, in an urban atmosphere over several hundred meters altitude. In paper [2], awarded as June 2014 OSA Spotlight, we identify the optical requirements ensuring an elastic lidar to be sensitive to new particles formation events (NPF-events) in the atmosphere, while, in the literature, all the ingredients initiating nucleation are still being unrevealed [3]. Both papers proceed with the same methodology by identifying the optical requirements from numerical simulation (Planck and Kirchhoff's laws in [1], Mie and T-matrix numerical codes in [2]), then presenting lidar field application case studies. We believe these new lidar methodologies may be useful for climate, geophysical, as well as fundamental purposes.

  1. A proteomic fingerprint of dissolved organic carbon and of soil particles.

    Science.gov (United States)

    Schulze, Waltraud X; Gleixner, Gerd; Kaiser, Klaus; Guggenberger, Georg; Mann, Matthias; Schulze, Ernst-Detlef

    2005-01-01

    Mass spectrometry-based proteomics was applied to analyze proteins isolated from dissolved organic matter (DOM). The focal question was to identify the type and biological origin of proteins in DOM, and to describe diversity of protein origin at the level of higher taxonomic units, as well as to detect extracellular enzymes possibly important in the carbon cycle. Identified proteins were classified according to their phylogenetic origin and metabolic function using the National Center for Biotechnology Information (NCBI) protein and taxonomy database. Seventy-eight percent of the proteins in DOM from the lake but less than 50% in forest soil DOM originated from bacteria. In a deciduous forest, the number of identified proteins decreased from 75 to 28 with increasing soil depth and decreasing total soil organic carbon content. The number of identified proteins and taxonomic groups was 50% higher in winter than in summer. In spruce forest, number of proteins and taxonomic groups decreased by 50% on a plot where trees had been girdled a year before and carbohydrate transport to roots was terminated. After girdling, proteins from four taxonomic groups remained as compared to nine taxonomic groups in healthy forest. Enzymes involved in degradation of organic matter were not identified in free soil DOM. However, cellulases and laccases were found among proteins extracted from soil particles, indicating that degradation of soil organic matter takes place in biofilms on particle surfaces. These results demonstrate a novel application of proteomics to obtain a "proteomic fingerprint" of presence and activity of organisms in an ecosystem.

  2. Particles that fight cancer: the use of protons and carbon ions in cancer therapy

    CERN Document Server

    CERN. Geneva

    2014-01-01

    Particles that fight cancer: the use of protons and carbon ions in cancer therapy Cancer is a major societal issue. A key challenge for cancer therapy is the complex and multifaceted nature of the disease, which calls for personalised treatment. Radiotherapy has been used to treat tumours for more than a century, and is still a staple in oncology: today, 50 % of cancer patients receive radiotherapy, half of them with curative intent. Hadrontherapy is one of the most technologically advanced methods of delivering radiation dose to the tumour while protecting surrounding healthy tissues. In addition, hadrontherapy can reach otherwise difficult to access deep-seated tumours and can be used for radio resistant tumours as in hypoxia. This year marks 60 years since the first patient was treated with protons in the US and 20 years since the use of carbon ions in Japan. Join us in learning about the journey of particle therapy in Japan and Europe, its challenges, clinical results and future prospects. Thursday 2...

  3. Magnetic carbon nanotubes with particle-free surfaces and high drug loading capacity.

    Science.gov (United States)

    Vermisoglou, Eleni C; Pilatos, George; Romanos, George E; Devlin, Eamon; Kanellopoulos, Nick K; Karanikolos, Georgios N

    2011-09-01

    Open-ended, multi-wall carbon nanotubes (CNTs) with magnetic nanoparticles encapsulated within their graphitic walls (magCNTs) were fabricated by a combined action of templated growth and a ferrofluid catalyst/carbon precursor, and tested as drug hosts. The hybrid nanotubes are stable under extreme pH conditions due to particle protection provided by the graphitic shell. The magCNTs are promising for high capacity drug loading given that the magnetic functionalization did not block any of the active sites available for drug attachment, either from the CNT internal void or on the internal and external surfaces. This is in contrast to typical approaches of loading CNTs with particles that proceed through surface attachment or capillary filling of the tube interior. Additionally, the CNTs exhibit enhanced hydrophilic character, as shown by water adsorption measurements, which make them suitable for biological applications. The morphological and structural characteristics of the hybrid CNTs are evaluated in conjunction to their magnetic properties and ability for drug loading (diaminophenothiazine). The fact that the magnetic functionality is provided from 'inside the walls' can allow for multimode functionalization of the graphitic surfaces and makes the magCNTs promising for targeted therapeutic applications. PMID:21817779

  4. Magnetic carbon nanotubes with particle-free surfaces and high drug loading capacity

    Energy Technology Data Exchange (ETDEWEB)

    Vermisoglou, Eleni C; Pilatos, George; Romanos, George E; Kanellopoulos, Nick K; Karanikolos, Georgios N [Institute of Physical Chemistry, Demokritos National Research Center, Athens 153 10 (Greece); Devlin, Eamon, E-mail: karanikolos@chem.demokritos.gr [Institute of Materials Science, Demokritos National Research Center, Athens 153 10 (Greece)

    2011-09-02

    Open-ended, multi-wall carbon nanotubes (CNTs) with magnetic nanoparticles encapsulated within their graphitic walls (magCNTs) were fabricated by a combined action of templated growth and a ferrofluid catalyst/carbon precursor, and tested as drug hosts. The hybrid nanotubes are stable under extreme pH conditions due to particle protection provided by the graphitic shell. The magCNTs are promising for high capacity drug loading given that the magnetic functionalization did not block any of the active sites available for drug attachment, either from the CNT internal void or on the internal and external surfaces. This is in contrast to typical approaches of loading CNTs with particles that proceed through surface attachment or capillary filling of the tube interior. Additionally, the CNTs exhibit enhanced hydrophilic character, as shown by water adsorption measurements, which make them suitable for biological applications. The morphological and structural characteristics of the hybrid CNTs are evaluated in conjunction to their magnetic properties and ability for drug loading (diaminophenothiazine). The fact that the magnetic functionality is provided from 'inside the walls' can allow for multimode functionalization of the graphitic surfaces and makes the magCNTs promising for targeted therapeutic applications.

  5. Acoustic and reservoir properties of microporous carbonate rocks: Implication of micrite particle size and morphology

    Science.gov (United States)

    Regnet, J. B.; Robion, P.; David, C.; Fortin, J.; Brigaud, B.; Yven, B.

    2015-02-01

    This integrated study provides significant insight into parameters controlling the acoustic and reservoir properties of microporous limestones, improving the knowledge of the relationships among petrophysic and microstructural content. Petrophysical properties measured from laboratory and logging tools (porosity, permeability, electrical conductivity, and acoustic properties) have been coupled with thin section and scanning electron microscope observations on the EST205 borehole from the Oxfordian limestone aquifer of the eastern part of the Paris Basin. A major achievement is the establishment of the link between micrite microtexture types (particle morphology and nature of intercrystal contacts) and the physical response, introducing a new effective and interesting rock-typing approach for microporous reservoirs. Fluid-flow properties are enhanced by the progressive augmentation of intercrystalline microporosity and associated pore throat diameter, as the coalescence of micrite particles decreases. Concerning acoustic properties, the slow increase of P wave velocity can be seen as a reflection of crystal size and growing contact cementation leading to a more cohesive and stiffer micrite microtexture. By applying poroelasticity theory on our samples, we show that velocity dispersion can be a very useful tool for data discrimination in carbonates. This dispersion analysis highlights the presence of microcracks in the rocks, and their overall effect on acoustic and transport properties. The presence of microcracks is also confirmed with observations and permeability measurements under high confining pressure. Finally, a possible origin of high porous levels in neritic limestones is a mineralogical transformation of carbonates through freshwater-related diagenesis during subaerial exposure time. Finally, by applying poroelasticity theory on our samples, we show that velocity dispersion can be a very useful tool for data discrimination in carbonates.

  6. Spectrally resolved efficiencies of carbon monoxide (CO photoproduction in the Western Canadian Arctic: particles versus solutes

    Directory of Open Access Journals (Sweden)

    G. Song

    2012-11-01

    Full Text Available Spectrally resolved efficiency (i.e. apparent quantum yield, AQY of carbon monoxide (CO photoproduction is a useful indicator of substrate photoreactivity and a crucial parameter for modeling CO photoproduction rates in the water column. Recent evidence has suggested that CO photoproduction from particles in marine waters is significant compared to the well-known CO production from chromophoric dissolved organic matter (CDOM photodegradation. Although CDOM-based CO AQY spectra have been extensively determined, little is known of this information on the particulate phase. Using water samples collected from the Mackenzie estuary, shelf, and Canada Basin in the Southeastern Beaufort Sea, the present study for the first time quantified the AQY spectra of particle-based CO photoproduction and compared them with the concomitantly determined CDOM-based CO AQY spectra. CO AQYs of both particles and CDOM decreased with wavelength but the spectral shape of the particulate AQY was flatter in the visible regime. This feature resulted in a disproportionally higher visible light-driven CO production by particles, thereby increasing the ratio of particle- to CDOM-based CO photoproduction with depth in the euphotic zone. In terms of depth-integrated production in the euphotic zone, CO formation from CDOM was dominated by the ultraviolet (UV, 290–400 nm radiation whereas UV and visible light played roughly equal roles in CO production from particles. Spatially, CO AQY of bulk particulate matter (i.e. the sum of organics and inorganics augmented from the estuary to shelf to basin while CO AQY of CDOM trended inversely. Water from the deep chlorophyll maximum layer revealed higher CO AQYs than did surface water for both particles and CDOM. CO AQY of bulk particulate matter exceeded that of CDOM on the shelf and in the basin but the sequence reversed in the estuary. Mineral absorption-corrected CO AQY of particulate organic matter (POM was, however, greater than

  7. Molecular dynamics study of the catalyst particle size dependence on carbon nanotube growth

    Science.gov (United States)

    Ding, Feng; Rosén, Arne; Bolton, Kim

    2004-08-01

    The molecular dynamics method, based on an empirical potential energy surface, was used to study the effect of catalyst particle size on the growth mechanism and structure of single-walled carbon nanotubes (SWNTs). The temperature for nanotube nucleation (800-1100 K), which occurs on the surface of the cluster, is similar to that used in catalyst chemical vapor deposition experiments, and the growth mechanism, which is described within the vapor-liquid-solid model, is the same for all cluster sizes studied here (iron clusters containing between 10 and 200 atoms were simulated). Large catalyst particles, which contain at least 20 iron atoms, nucleate SWNTs that have a far better tubular structure than SWNTs nucleated from smaller clusters. In addition, the SWNTs that grow from the larger clusters have diameters that are similar to the cluster diameter, whereas the smaller clusters, which have diameters less than 0.5 nm, nucleate nanotubes that are ≈0.6-0.7 nm in diameter. This is in agreement with the experimental observations that SWNT diameters are similar to the catalyst particle diameter, and that the narrowest free-standing SWNT is 0.6-0.7 nm.

  8. Anti-corrosive Effects of Multi-Walled Carbon Nano Tube and Zinc Particle Shapes on Zinc Ethyl Silicate Coated Carbon Steel

    Energy Technology Data Exchange (ETDEWEB)

    Jang, JiMan; Shon, MinYoung; Kwak, SamTak [Pukyong National University, Busan (Korea, Republic of)

    2016-01-15

    Zinc ethyl silicate coatings containing multi walled carbon nanotubes (MWCNTs) were prepared, to which we added spherical and flake shaped zinc particles. The anti-corrosive effects of MWCNTs and zinc shapes on the zinc ethyl silicate coated carbon steel was examined, using electrochemical impedance spectroscopy and corrosion potential measurement. The results of EIS and corrosion potential measurement showed that the zinc ethyl silicate coated with flake shaped zinc particles and MWCNT showed lesser protection to corrosion. These outcomes were in agreement with previous results of corrosion potential and corrosion occurrence.

  9. Springtime carbon episodes at Gosan background site revealed by total carbon, stable carbon isotopic composition, and thermal characteristics of carbonaceous particles

    Directory of Open Access Journals (Sweden)

    J. Jung

    2011-05-01

    Full Text Available In order to investigate the carbon episodes at Gosan background super-site (33.17° N, 126.10° E in East Asia during spring of 2007 and 2008, total suspended particles (TSP were collected and analyzed for particulate organic carbon, elemental carbon, total carbon (TC, total nitrogen (TN, and stable carbon isotopic composition (δ13C of TC. The carbon episodes at the Gosan site were categorized as long-range transported anthropogenic pollutant (LTP from Asian continent, Asian dust (AD accompanying with LTP, and local pollen episodes. The stable carbon isotopic composition of TC (δ13CTC was found to be lowest during the pollen episodes (range: −26.2 ‰ to −23.5 ‰, avg.: −25.2 ± 0.9 ‰, followed by the LTP episodes (range: −23.5 ‰ to −23.0 ‰, avg.: −23.3 ± 0.3 ‰ and the AD episodes (range: −23.3 to −20.4 %, avg.: −21.8 ± 2.0 ‰. The δ13CTC of the airborne pollens (−28.0 ‰ collected at the Gosan site showed value similar to that of tangerine fruit (−28.1 ‰ produced from Jeju Island. Based on the carbon isotope mass balance equation and the TN and TC regression approach, we found that ∼40–45 % of TC in the TSP samples during the pollen episodes was attributed to airborne pollens from Japanese cedar trees planted around tangerine farms in Jeju Island. The δ13C of citric acid in the airborne pollens (−26.3 ‰ collected at the Gosan site was similar to that in tangerine fruit (−27.4 ‰. The negative correlation between the citric acid-carbon/TC ratios and δ13CTC were obtained during the pollen episodes. These results suggest that citric acid emitted from tangerine fruit may be adsorbed on the airborne pollens and then transported to the Gosan site. Based on the thermal evolution pattern of organic aerosols during the carbon episodes, we found that organic aerosols originated from East China are more volatile on

  10. Concentrations of fine, ultrafine, and black carbon particles in auto-rickshaws in New Delhi, India

    Science.gov (United States)

    Apte, Joshua, S.; Kirchstetter, Thomas W.; Reich, Alexander, H.; Deshpande, Shyam J.; Kaushik, Geetanjali; Chel, Arvind; Marshall, Julian D.; Nazaroff, William W.

    2011-08-01

    Concentrations of air pollutants from vehicles are elevated along roadways, indicating that human exposure in transportation microenvironments may not be adequately characterized by centrally located monitors. We report results from ˜180 h of real-time measurements of fine particle and black carbon mass concentration (PM 2.5, BC) and ultrafine particle number concentration (PN) inside a common vehicle, the auto-rickshaw, in New Delhi, India. Measured exposure concentrations are much higher in this study (geometric mean for ˜60 trip-averaged concentrations: 190 μg m -3 PM 2.5, 42 μg m -3 BC, 280 × 10 3 particles cm -3; GSD ˜1.3 for all three pollutants) than reported for transportation microenvironments in other megacities. In-vehicle concentrations exceeded simultaneously measured ambient levels by 1.5× for PM 2.5, 3.6× for BC, and 8.4× for PN. Short-duration peak concentrations (averaging time: 10 s), attributable to exhaust plumes of nearby vehicles, were greater than 300 μg m -3 for PM 2.5, 85 μg m -3 for BC, and 650 × 10 3 particles cm -3 for PN. The incremental increase of within-vehicle concentration above ambient levels—which we attribute to in- and near-roadway emission sources—accounted for 30%, 68% and 86% of time-averaged in-vehicle PM 2.5, BC and PN concentrations, respectively. Based on these results, we estimate that one's exposure during a daily commute by auto-rickshaw in Delhi is as least as large as full-day exposures experienced by urban residents of many high-income countries. This study illuminates an environmental health concern that may be common in many populous, low-income cities.

  11. Hypoxia in Tumor Angiogenesis and Metastasis: Evaluation of VEGF and MMP Over-expression and Down-Regulation of HIF-1alpha with RNAi in Hypoxic Tumor Cells

    Science.gov (United States)

    Shah, Shruti

    Background: As tumor mass grows beyond a few millimeters in diameter, the angiogenic "switch" is turned on leading to recruitment of blood vessels from surrounding artery and veins. However, the tumor mass is poorly perfused and there are pockets of hypoxia or lower oxygen concentrations relative to normal tissue. Hypoxia-inducing factor-1a (HIF-1a), a transcription factor, is activated when the oxygen concentration is low. Upon activation of HIF-1a, a number of other genes also turn on that allows the tumor to become more aggressive and resistant to therapy. Purpose: The main objectives of this study were to evaluate the effect of hypoxia-induced HIF-1a followed by over-expression of angiogenic and metastatic markers in tumor cells and down-regulation of HIF-1a using nanoparticle-delivered RNA interference therapy. Methods: Human ovarian (SKOV3) and breast (MDA-MB-231) adenocarcinoma cells were incubated under normoxic and hypoxic conditions. Following hypoxia treatment of the cells, HIF-1α, vascular endothelial growth factor (VEGF), matrix metalloproteinase 2 (MMP-2), and MMP-9 expression was analyzed qualitatively and quantitatively. For intracellular delivery of HIF-1a gene silencing small interfering RNA (siRNA), type B gelatin nanoparticles were fabricated using the solvent displacement method and the surface was modified with poly(ethylene glycol) (PEG, Mol. wt. 2kDa). Cellular uptake and distribution of the nanoparticles was observed with Cy3-siRNA loaded, FITC-conjugated gelatin nanoparticles. Cytotoxicity of the nanoparticle formulations was evaluated in both the cell lines. siRNA was transfected in the gelatin nanoparticles under hypoxic conditions. Total cellular protein and RNA were extracted for analysis of HIF1a, VEGF, MMP-2 and MMP-9 expression. Results: MDA-MB-231 and SKOV3 cells show increased expression of HIF1a under hypoxic conditions compared to baseline levels at normoxic conditions. ELISA and western blots of VEGF, MMP-2 and MMP-9 appear to

  12. Morphology, chemical composition and nanostructure of single carbon-rich particles studied by transmission electron microscopy: source apportionment in workroom air of aluminium smelters.

    Science.gov (United States)

    Weinbruch, Stephan; Benker, Nathalie; Kandler, Konrad; Ebert, Martin; Ellingsen, Dag G; Berlinger, Balázs; Thomassen, Yngvar

    2016-02-01

    Sources of C-rich particles at work places in two aluminium smelters in Norway were studied by transmission electron microscopy and energy-dispersive X-ray microanalysis. Based on morphology, nanostructure and chemistry, three different types of C-rich particles are distinguished: (a) chain-like agglomerates (70-100% by number, relative to the sum of C-rich particles) consisting of primary particles with typical onion-shell structure of graphene layers, (b) multi-walled carbon nanotube particles (≈3%) and (c) spheres or agglomerates of amorphous C-rich particles (0-30%). Chain-like agglomerates are interpreted as diesel soot in accordance with literature data on primary particle diameter, chemical composition and nanostructure of primary particles. The source of the observed multi-walled carbon nanotubes is not known. The amorphous C-rich particles most likely consist of organic carbon species which cannot be characterized further by X-ray microanalysis. Unaltered graphitic electrode material was not found among the C-rich particles. The high fraction of diesel soot particles indicates that elemental carbon is generally suited as proxy for diesel soot in aluminium smelters. However, due to the presence of carbon nanotubes and amorphous C-rich particles, detailed characterization of sources of carbon-rich particles by electron microscopy is recommended for accurate assessment of adverse health effects. PMID:26637216

  13. Specific down-regulation of spermatogenesis genes targeted by 22G RNAs in hybrid sterile males associated with an X-Chromosome introgression.

    Science.gov (United States)

    Li, Runsheng; Ren, Xiaoliang; Bi, Yu; Ho, Vincy Wing Sze; Hsieh, Chia-Ling; Young, Amanda; Zhang, Zhihong; Lin, Tingting; Zhao, Yanmei; Miao, Long; Sarkies, Peter; Zhao, Zhongying

    2016-09-01

    Hybrid incompatibility (HI) prevents gene flow between species, thus lying at the heart of speciation genetics. One of the most common HIs is male sterility. Two superficially contradictory observations exist for hybrid male sterility. First, an introgression on the X Chromosome is more likely to produce male sterility than on autosome (so-called large-X theory); second, spermatogenesis genes are enriched on the autosomes but depleted on the X Chromosome (demasculinization of X Chromosome). Analysis of gene expression in Drosophila hybrids suggests a genetic interaction between the X Chromosome and autosomes that is essential for male fertility. However, the prevalence of such an interaction and its underlying mechanism remain largely unknown. Here we examine the interaction in nematode species by contrasting the expression of both coding genes and transposable elements (TEs) between hybrid sterile males and its parental nematode males. We use two lines of hybrid sterile males, each carrying an independent introgression fragment from Caenorhabditis briggsae X Chromosome in an otherwise Caenorhabditis nigoni background, which demonstrate similar defects in spermatogenesis. We observe a similar pattern of down-regulated genes that are specific for spermatogenesis between the two hybrids. Importantly, the down-regulated genes caused by the X Chromosome introgressions show a significant enrichment on the autosomes, supporting an epistatic interaction between the X Chromosome and autosomes. We investigate the underlying mechanism of the interaction by measuring small RNAs and find that a subset of 22G RNAs specifically targeting the down-regulated spermatogenesis genes is significantly up-regulated in hybrids, suggesting that perturbation of small RNA-mediated regulation may contribute to the X-autosome interaction.

  14. Proteomic identification of non-erythrocytic alpha-spectrin-1 down-regulation in the pre-optic area of neonatally estradiol-17β treated female adult rats.

    Science.gov (United States)

    Govindaraj, Vijayakumar; Rao, Addicam Jagannadha

    2016-06-01

    It is well established that sexually dimorphic brain regions, which are critical for reproductive physiology and behavior, are organized by steroid hormones during the first 2 weeks after birth in the rodents. In our recent observation, neonatal exposure to estradiol-17β (E2) in the female rat revealed increase in cyclooxygenase 2 (COX-2) level, sexually dimorphic nucleus (SDN)-pre-optic area (POA) size and down-regulation of synaptogenesis related genes in POA in the adult stage. In the present study, using the same animal model, the protein profile of control and neonatally E2-treated POA was compared by 1D-SDS-PAGE, and the protein that shows a change in abundance was identified by LC-MS/MS analysis. Results indicated that there was a single protein band, which was down-regulation in E2-treated POA and it was identified as spectrin alpha chain, non-erythrocytic 1 (SPTAN1). Consistently, the down-regulation of SPTAN1 expression was also confirmed by reverse transcription polymerase chain reaction (RT-PCR) and Western blot analysis. The SPTAN1 was identified as a cytoskeletal protein that is involved in stabilization of the plasma membrane and organizes intracellular organelles, and it has been implicated in cellular functions including DNA repair and cell cycle regulation. The evidence shows that any mutation in spectrins causes impairment of synaptogenesis and other neurological disorders. Also, protein-protein interaction analysis of SPTAN1 revealed a strong association with proteins such as kirrel, actinin, alpha 4 (ACTN4) and vinculin (VCL) which are implicated in sexual behavior, masculinization and defeminization. Our results indicate that SPTAN1 expression in the developing rat brain is sexually dimorphic, and we suggest that this gene may mediate E2-17β-induced masculinization and defeminization, and disrupted reproductive function in the adult stage. PMID:27166725

  15. Nicotine-induced retardation of chondrogenesis through down-regulation of IGF-1 signaling pathway to inhibit matrix synthesis of growth plate chondrocytes in fetal rats

    Energy Technology Data Exchange (ETDEWEB)

    Deng, Yu; Cao, Hong; Cu, Fenglong [Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Xu, Dan [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Research Center of Food and Drug Evaluation, Wuhan University, Wuhan 430071 (China); Lei, Youying [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Tan, Yang [Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Magdalou, Jacques [UMR 7561 CNRS-Nancy Université, Faculté de Médicine, Vandoeuvre-lès-Nancy (France); Wang, Hui [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Research Center of Food and Drug Evaluation, Wuhan University, Wuhan 430071 (China); Chen, Liaobin, E-mail: lbchen@whu.edu.cn [Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China)

    2013-05-15

    Previous studies have confirmed that maternal tobacco smoking causes intrauterine growth retardation (IUGR) and skeletal growth retardation. Among a multitude of chemicals associated with cigarette smoking, nicotine is one of the leading candidates for causing low birth weights. However, the possible mechanism of delayed chondrogenesis by prenatal nicotine exposure remains unclear. We investigated the effects of nicotine on fetal growth plate chondrocytes in vivo and in vitro. Rats were given 2.0 mg/kg·d of nicotine subcutaneously from gestational days 11 to 20. Prenatal nicotine exposure increased the levels of fetal blood corticosterone and resulted in fetal skeletal growth retardation. Moreover, nicotine exposure induced the inhibition of matrix synthesis and down-regulation of insulin-like growth factor 1 (IGF-1) signaling in fetal growth plates. The effects of nicotine on growth plates were studied in vitro by exposing fetal growth plate chondrocytes to 0, 1, 10, or 100 μM of nicotine for 10 days. Nicotine inhibited matrix synthesis and down-regulated IGF-1 signaling in chondrocytes in a concentration-dependent manner. These results suggest that prenatal nicotine exposure induces delayed chondrogenesis and that the mechanism may involve the down-regulation of IGF-1 signaling and the inhibition of matrix synthesis by growth plate chondrocytes. The present study aids in the characterization of delayed chondrogenesis caused by prenatal nicotine exposure, which might suggest a candidate mechanism for intrauterine origins of osteoporosis and osteoarthritis. - Highlights: ► Prenatal nicotine-exposure could induce delayed chondrogenesis in fetal rats. ► Nicotine inhibits matrix synthesis of fetal growth plate chondrocytes. ► Nicotine inhibits IGF-1 signaling pathway in fetal growth plate chondrocytes.

  16. Ovarian down Regulation by GnRF Vaccination Decreases Reproductive Tract Tumour Size in Female White and Greater One-Horned Rhinoceroses

    Science.gov (United States)

    Hermes, Robert; Schwarzenberger, Franz; Göritz, Frank; Oh, Serena; Fernandes, Teresa; Bernardino, Rui; Leclerc, Antoine; Greunz, Eva; Mathew, Abraham; Forsyth, Sarah; Saragusty, Joseph; Hildebrandt, Thomas Bernd

    2016-01-01

    Reproductive tract tumours, specifically leiomyoma, are commonly found in female rhinoceroses. Similar to humans, tumour growth in rhinoceroses is thought to be sex hormone dependent. Tumours can form and expand from the onset of ovarian activity at puberty until the cessation of sex-steroid influences at senescence. Extensive tumour growth results in infertility. The aim of this study was to down regulate reproductive function of tumour-diseased and infertile females to stop further tumour growth using a Gonadotropin releasing factor (GnRF) vaccine. Four infertile southern white (Ceratotherium simum simum) and three Greater one-horned rhinoceroses (rhinoceros unicornis) with active ovaries and 2.7 ± 0.9 and 14.0 ± 1.5 reproductive tract tumours respectively were vaccinated against GnRF (Improvac®, Zoetis, Germany) at 0, 4 and 16 weeks and re-boostered every 6–8 months thereafter. After GnRF vaccination ovarian and luteal activity was suppressed in all treated females. Three months after vaccination the size of the ovaries, the number of follicles and the size of the largest follicle were significantly reduced (P<0.03). Reproductive tract tumours decreased significantly in diameter (Greater-one horned rhino: P<0.0001; white rhino: P<0.01), presumably as a result of reduced sex-steroid influence. The calculated tumour volumes were reduced by 50.8 ± 10.9% in Greater one-horned and 48.6 ± 12.9% in white rhinoceroses. In conclusion, GnRF vaccine effectively down regulated reproductive function and decreased the size of reproductive tract tumours in female rhinoceros. Our work is the first to use down regulation of reproductive function as a symptomatic treatment against benign reproductive tumour disease in a wildlife species. Nonetheless, full reversibility and rhinoceros fertility following GnRF vaccination warrants further evaluation. PMID:27403662

  17. Down-regulation of cold-inducible RNA-binding protein does not improve hypothermic growth of Chinese hamster ovary cells producing erythropoietin.

    Science.gov (United States)

    Hong, Jong Kwang; Kim, Yeon-Gu; Yoon, Sung Kwan; Lee, Gyun Min

    2007-03-01

    Discovery of the cold-inducible RNA-binding protein (CIRP) in mouse fibroblasts suggests that growth suppression at hypothermic conditions is due to an active response by the cell rather than due to passive thermal effects. To determine the effect of down-regulated CIRP expression on cell growth and erythropoietin (EPO) production in recombinant Chinese hamster ovary (rCHO) cells at low culture temperature, stable CHO cell clones with reduced CIRP expression level were established by transfecting (rCHO) cells with the CIRP siRNA vector with a target sequence of TCGTCCTTCCATGGCTGTA. For comparison of the degree of specific growth rate (micro) reduction at low culture temperature, three CIRP-reduced clones with different mu and three control clones transfected with null vector were cultivated at two different temperatures, 32 degrees C and 37 degrees C. Unlike mouse fibroblasts, alleviation of hypothermic growth arrest of rCHO cells by CIRP down-regulation was insignificant, as shown by statistical analysis using the t-test (P<0.18, n=3). The ratios of mu at 32 degrees C to micro at 37 degrees C of CIRP-reduced clones and control clones were 0.29+/-0.03 and 0.25+/-0.03 on an average, respectively. Furthermore, it was also found that overexpression of CIRP did not inhibit rCHO cell growth significantly at 37 degrees C. Taken together, the data obtained show that down-regulation of only CIRP in rCHO cells, unlike mouse fibroblasts, is not sufficient to recover growth arrest at low-temperature culture (32 degrees C). PMID:17239640

  18. Chemically Synthesised Pt Particles on Surface Oxidized Carbon Nanotubes as an Effective Catalyst for Direct Methanol Fuel Cell

    Institute of Scientific and Technical Information of China (English)

    Mohammad; yari; Sajjad; Sadaghat; Sharehjini

    2007-01-01

    1 Results The synthesis, physical characterization and electrochemical analysis of Pt particles prepared using the surface oxidized carbon nanotubes prepared by chemically anchoring Pt onto the surface of the CNTs with 2.0 mol/L HNO3 by refluxing for 10 h to introduce surface functional groups.The particles of Pt are synthesized by reduction with sodium borohydride of H2PtCl6. The electro-oxidation of liquid methanol of this catalyst as a thin layer on glassy carbon electrode is investigated at room te...

  19. Sensitivity of the Single Particle Soot Photometer to different black carbon types

    Directory of Open Access Journals (Sweden)

    M. Laborde

    2012-05-01

    Full Text Available Black carbon (BC is now mainly of anthropogenic origin. It is the dominant light absorbing component of atmospheric aerosols, playing an important role in the earth's radiative balance and therefore relevant to climate change studies. In addition, BC is known to be harmful to human beings making it relevant to policy makers. Nevertheless, the measurement of BC remains biased by the instrument-based definition of BC. The Single Particle Soot Photometer (SP2, allows the measurement of the refractory BC (rBC mass of individual particles using laser-induced incandescence. However, the SP2 needs an empirical calibration to retrieve the rBC mass from the incandescence signal and the sensitivity of the SP2 differs between different BC types. Ideally, for atmospheric studies, the SP2 should be calibrated using ambient particles containing a known mass of ambient rBC. However, such "ambient BC" calibration particles cannot easily be obtained and thus commercially available BC particles are commonly used for SP2 calibration instead. In this study we tested the sensitivity of the SP2 to different BC types in order to characterize the potential error introduced by using non-ambient BC for calibration. The sensitivity of the SP2 was determined, using an aerosol particle mass analyzer, for rBC from thermodenuded diesel exhaust, wood burning exhaust and ambient particles as well as for commercially available products: Aquadag® and fullerene soot.

    Thermodenuded, fresh diesel exhaust has been found to be ideal for SP2 calibration for two reasons. First, the small amount of non-BC matter upon emission reduces the risk of bias due to incomplete removal of non-BC matter and second, it is considered to represent atmospheric rBC in urban locations where diesel exhaust is the main source of BC. The SP2 was found to be up to 16% less sensitive to rBC from thermodenuded ambient particles (≤15 fg than rBC from diesel exhaust, however, at least part

  20. Impact of electron irradiation on particle track etching response in polyallyl diglycol carbonate (PADC)

    Indian Academy of Sciences (India)

    R Mishra; S P Tripathy; A Kulshrestha; A Srivastava; S Ghosh; K K Dwivedi; D T Khathing; M Müller; D Fink

    2000-05-01

    In the present work, attempts have been made to investigate the modification in particle track etching response of polyallyl diglycol carbonate (PADC) due to impact of 2 MeV electrons. PADC samples pre-irradiated to 1, 10, 20, 40, 60, 80 and 100 Mrad doses of 2 MeV electrons were further exposed to 140 MeV 28Si beam and dose-dependent track registration properties of PADC have been studied. Etch-rate values of the PADC irradiated to 100 Mrad dose electron was found to increase by nearly 4 times that of pristine PADC. The electron irradiation has promoted chain scissioning in PADC, thereby converting the polymer into an easily etchable polymer. Moreover, the etching response and the detection efficiency were found to improve by electron irradiation. Scanning electron microscopy of etched samples further revealed the surface damage in these irradiated PADCs

  1. A New Method for Descaling Wool Fibres by Nano Abrasive Calcium Carbonate Particles in Ultrasonic Bath

    Directory of Open Access Journals (Sweden)

    Ali rezaghasemi

    2016-08-01

    Full Text Available Up to now, the most conventional methods for descaling of wool fibre are based on chemical degradation and resin covering of scales or a combination of them. These methods are producing wastewater and can cover physical properties of the fibres beside scales orderly. In this study, a new and clean method is developed on the basis of abrasion effect of calcium carbonate Nano particles (CCNP in an ultrasonic bath. Woolen Samples (fibre and yarn were sonicated with different levels of CCNP. Tensile properties of the yarns, directional friction effect of the fibres and scanning electron microscope images of the fibres were studied. Test results showed that sonicated Nano treatment of woolyarn reduced its tenacity, extension and work of rupture and increased its coefficient of friction. Scanning electron microscope images of fibres and measurement of fibres directional displacement confirmed descaling of Nano abrasive treated wool samples in comparison to the raw wool.

  2. MicroRNA-26a is Strongly Down-regulated in Melanoma and Induces Cell Death through Repression of Silencer of Death Domains (SODD)

    OpenAIRE

    Reuland, Steven N.; Smith, Shilo; Bemis, Lynne; Goldstein, Nathaniel B.; Almeida, Adam; Katie A. Partyka; Marquez, Victor E.; Zhang, Qinghong; David A Norris; Yiqun G Shellman

    2012-01-01

    Melanoma is an aggressive cancer that metastasizes rapidly, and is refractory to conventional chemotherapies. Identifying miRNAs that are responsible for this pathogenesis is therefore a promising means of developing new therapies. We identified miR-26a through microarray and qRT-PCR experiments as an miRNA that is strongly down-regulated in melanoma cell lines as compared to primary melanocytes. Treatment of cell lines with miR-26a mimic caused significant and rapid cell death compared to a ...

  3. Enterococcus faecalis Infection and Reactive Oxygen Species Down-Regulates the miR-17-92 Cluster in Gastric Adenocarcinoma Cell Culture

    DEFF Research Database (Denmark)

    Strickertsson, Jesper A B; Rasmussen, Lene Juel; Friis-Hansen, Lennart

    2014-01-01

    Chronic inflammation due to bacterial overgrowth of the stomach predisposes to the development of gastric cancer and is also associated with high levels of reactive oxygen species (ROS). In recent years increasing attention has been drawn to microRNAs (miRNAs) due to their role in the pathogenesis...... by living E. faecalis bacteria caused a significant global response in miRNA expression in the MKN74 cell culture. E. faecalis infection as well as ROS stimulation down-regulated the expression of the miR-17-92 cluster. We believe that these changes could reflect a general response of gastric epithelial...

  4. Anti-rat soluble IL-6 receptor antibody down-regulates cardiac IL-6 and improves cardiac function following trauma-hemorrhage.

    Science.gov (United States)

    Yang, Shaolong; Hu, Shunhua; Choudhry, Mashkoor A; Rue, Loring W; Bland, Kirby I; Chaudry, Irshad H

    2007-03-01

    Although anti-IL-6-mAb down-regulates cardiac IL-6 and attenuates IL-6-mediated cardiac dysfunction following trauma-hemorrhage, it is not known whether blockade of IL-6 receptor will down-regulate cardiac IL-6 and improve cardiac function under those conditions. Six groups of male adult rats (275-325 g) were used: sham/trauma-hemorrhage+vehicle, sham/trauma-hemorrhage+IgG, sham/trauma-hemorrhage+anti-rat sIL-6R. Rats underwent trauma-hemorrhage (removal of 60% of the circulating blood volume and fluid resuscitation after 90 min). Vehicle (V), normal goat IgG or anti-rat sIL-6R (16.7 microg/kg BW) was administered intra-peritoneally in the middle of resuscitation. Two hours later, cardiac function was measured by ICG dilution technique; blood samples collected, cardiomyocytes isolated, and cardiomyocyte nuclei were then extracted. Cardiac IL-6, IL-6R, gp130, IkappaB-alpha/P-IkappaB-alpha, NF-kappaB, and ICAM-1 expressions were measured by immunoblotting. Plasma IL-6 and cardiomyocyte NF-kappaB DNA-binding activity were determined by ELISA. In additional animals, heart harvested and cardiac MPO activity and CINC-1 and -3 were also measured. In another group of rats, cardiac function was measure by microspheres at 24 h following trauma-hemorrhage. Cardiac function was depressed and cardiac IL-6, P-IkappaB-alpha, NF-kappaB and its DNA-binding activity, ICAM-1, MPO activity, and CINC-1 and -3 were markedly increased after trauma-hemorrhage. Moreover, cardiac dysfunction was evident even 24 h after trauma-hemorrhage. Administration of sIL-6R following trauma-hemorrhage: (1) improved cardiac output at 2 h and 24 h (p<0.05); (2) down-regulated both cardiac IL-6 and IL-6R (p<0.05); and (3) attenuated cardiac P-IkappaB-alpha, NF-kappaB, NF-kappaB DNA-binding activity, ICAM-1, CINC-1, -3, and MPO activity (p<0.05). IgG did not significantly influence the above parameters. Thus, IL-6-mediated up-regulation of cardiac NF-kappaB, ICAM-1, CINC-1, -3, and MPO activity likely

  5. SKP2 siRNA inhibits the degradation of P27kip1 and down-regulates the expression of MRP in HL-60/A cells

    Institute of Scientific and Technical Information of China (English)

    Jie Xiao; Songmei Yin; Yiqing Li; Shuangfeng Xie; Danian Nie; Liping Ma; Xiuju Wang; Yudan Wu; Jianhong Feng

    2009-01-01

    S-phase kinase-associated protein 2 (SKP2) gene is a tumor suppressor gene, and is involved in the ubiquitin-mediated degradation of P27kip1. SKP2 and P27kip1 affect the proceeding and prognosis of leukemia through regulating the proliferation, apoptosis and differentiation of leukemia cells. In this study, we explored the mechan-ism of reversing of HL-60/A drug resistance through SKP2 down-regulation. HL-60/A cells were nucleofected by Amaxa Nucleofector System with SKP2 siRNA. The gene and protein expression levels of Skp2, P27kip1, and multi-drug resistance associated protein (MRP) were determined by reverse transcription-polymerase chain reaction and western blot analysis, respectively. The cell cycle was analyzed by flow cytometry. The 50% inhibi-tory concentration value was calculated using cytotoxic analysis according to the death rate of these two kinds of cells under different concentrations of chemotherapeutics to compare the sensitivity of the cells. HL-60/A cells showed multi-drug resistance phenotype characteristic by cross-resistance to adriamycin, daunorubicin, and arabi-nosylcytosine, due to the expression of MRP. We found that the expression of SKP2 was higher in HL-60/A cells than in HL-60 cells, but the expression of P27kip1 was lower. The expression of SKP2 in HL-60/A cells nucleo-fected by SKP2 siRNA was down-regulated whereas the protein level of P27kip1 was up-regulated. Compared with the MRP expression level in the control group (nucleo-fected by control siRNA), the mRNA and protein expression levels of MRP in HL-60/A cells nucleofected by SKP2 siRNA were lower, and the latter cells were more sensitive to adriamycin, daunorubicin, and arabi-nosylcytosine. Down-regulating the SKP2 expression and arresting cells in the G0/G1 phase improve drug sensitivity of leukemia cells with down-regulated MRP expression.

  6. Hypoxia-mediated down-regulation of Bid and Bax in tumors occurs via hypoxia-inducible factor 1-dependent and -independent mechanisms and contributes to drug resistance

    DEFF Research Database (Denmark)

    Erler, Janine Terra; Cawthorne, Christopher J; Williams, Kaye J;

    2004-01-01

    of the Bcl-2 protein family. Oxygen deprivation of human colon cancer cells in vitro provoked decreased mRNA and protein levels of proapoptotic Bid and Bad. Hypoxia-inducible factor 1 (HIF-1) was dispensable for the down-regulation of Bad but required for that of Bid, consistent with the binding of HIF-1......alpha to a hypoxia-responsive element (positions -8484 to -8475) in the bid promoter. Oxygen deprivation resulted in proteosome-independent decreased expression of Bax in vitro, consistent with a reduction in global translation efficiency. The physiological relevance of Bid and Bax down...

  7. Molecular mechanisms of benzodiazepine-induced down-regulation of GABAA receptor alpha 1 subunit protein in rat cerebellar granule cells.

    OpenAIRE

    Brown, M. J.; Bristow, D. R.

    1996-01-01

    1. Chronic benzodiazepine treatment of rat cerebellar granule cells induced a transient down-regulation of the gamma-aminobutyric acidA (GABAA) receptor alpha 1 subunit protein, that was dose-dependent (1 nM-1 microM) and prevented by the benzodiazepine antagonist flumazenil (1 microM). After 2 days of treatment with 1 microM flunitrazepam the alpha 1 subunit protein was reduced by 41% compared to untreated cells, which returned to, and remained at, control cell levels from 4-12 days of treat...

  8. Hypothermia rescues hippocampal CA1 neurons and attenuates down-regulation of the AMPA receptor GluR2 subunit after forebrain ischemia

    OpenAIRE

    Colbourne, Frederick; Grooms, Sonja Y.; Zukin, R. Suzanne; Buchan, Alastair M.; Bennett, Michael V. L.

    2003-01-01

    Brief forebrain ischemia in rodents induces selective and delayed neuronal death, particularly of hippocampal CA1 pyramidal neurons. Neuronal death is preceded by down-regulation specific to CA1 of GluR2, the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunit that limits Ca2+ influx. This alteration is hypothesized to cause neurodegeneration by permitting a lethal influx of Ca2+ and/or Zn2+ through newly formed GluR2-lacking AMPA receptors. Two days of mild hypotherm...

  9. miR-24 functions as a tumor suppressor in Hep2 laryngeal carcinoma cells partly through down-regulation of the S100A8 protein

    OpenAIRE

    Guo, Yan; FU, WEINENG; Chen, Hong; Shang, Chao; Zhong, Ming

    2011-01-01

    microRNAs, a family of small non-coding RNAs, regulating approximately 30% of all human genes are deeply involved in the pathogenesis of several types of cancers, including laryngeal squamous cell carcinoma (LSCC). Here, we demonstrate that miR-24 is down-regulated in human LSCC tissues. Ectopic expression of miR-24 in Hep2 cells significantly induced cell morphology changes and inhibited cell proliferation and invasion ability in vitro by targeting S100A8 at the translational level. Meanwhil...

  10. Down-regulation of the strawberry Bet v 1-homologous allergen in concert with the flavonoid biosynthesis pathway in colorless strawberry mutant

    DEFF Research Database (Denmark)

    Hjernø, Karin; Alm, Rikard; Canbäck, Björn;

    2006-01-01

    to the nomenclature for allergen proteins, showed sequence identity of 54 and 77%, respectively, with corresponding allergens from birch and apple. Differential expression, as evaluated by 2-D DIGE, occurred in 10% of protein spots when red strawberries were compared to a colorless (white) strawberry mutant. White...... strawberries, known to be tolerated by individuals affected by allergy, were found to be virtually free from the strawberry allergen. Also several enzymes in the pathway for biosynthesis of flavonoids, to which the red color pelargonidin belongs, were down-regulated. This approach to assess differential...

  11. Transmembrane neural cell-adhesion molecule (NCAM), but not glycosyl-phosphatidylinositol-anchored NCAM, down-regulates secretion of matrix metalloproteinases

    DEFF Research Database (Denmark)

    Edvardsen, K; Chen, W; Rucklidge, G;

    1993-01-01

    proteinases, and proteinase inhibitors all participate in the construction, maintenance, and remodeling of extracellular matrix by cells. The neural cell-adhesion molecule (NCAM)-negative rat glioma cell line BT4Cn secretes substantial amounts of metalloproteinases, as compared with its NCAM-positive mother...... cell line BT4C. We have transfected the BT4Cn cell line with cDNAs encoding the human NCAM-B and -C isoforms. We report here that the expression of transmembrane NCAM-B, but not of glycosyl-phosphatidylinositol-linked NCAM-C, induces a down-regulation of 92-kDa gelatinase (matrix metalloproteinase 9...

  12. 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

    . 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...... arteries down-regulates VSMC TP receptor expression through activation of ERK1/2 and p38/NF-kappaB signal pathways....

  13. 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

    . 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...... arteries down-regulates VSMC TP receptor expression through activation of ERK1/2 and p38/NF-kappaB signal pathways....

  14. Growth promotion in pigs by oxytetracycline coincides with down regulation of serum inflammatory parameters and of hibernation-associated protein HP-27

    DEFF Research Database (Denmark)

    Soler, Laura; Miller, Ingrid; Hummel, Karin;

    2016-01-01

    The growth promoting effect of supplementing animal feed with antibiotics like tetracycline has traditionally been attributed to their antibiotic character. However, more evidence has been accumulated on their direct anti-inflammatory effect during the last two decades. Here we used a pig model...... and lipid metabolism, confirming the anti-inflammatory mechanism of OTC. Interestingly, apart from the classic acute phase reactants also down regulation was seen of a hibernation associated plasma protein (HP-27), which is to our knowledge the first description in pigs. Although the exact function in non...

  15. Lack of acute phase response in the livers of mice exposed to diesel exhaust particles or carbon black by inhalation

    OpenAIRE

    Williams Andrew; Møller Peter; Boisen Anne; Bornholdt Jette; Folkmann Janne K; Halappanavar Sabina; Saber Anne T; Yauk Carole; Vogel Ulla; Loft Steffen; Wallin Håkan

    2009-01-01

    Abstract Background Epidemiologic and animal studies have shown that particulate air pollution is associated with increased risk of lung and cardiovascular diseases. Although the exact mechanisms by which particles induce cardiovascular diseases are not known, studies suggest involvement of systemic acute phase responses, including C-reactive protein (CRP) and serum amyloid A (SAA) in humans. In this study we test the hypothesis that diesel exhaust particles (DEP) – or carbon black (CB)-induc...

  16. Collection efficiency of the soot-particle aerosol mass spectrometer (SP-AMS) for internally mixed particulate black carbon

    Science.gov (United States)

    Willis, M. D.; Lee, A. K. Y.; Onasch, T. B.; Fortner, E. C.; Williams, L. R.; Lambe, A. T.; Worsnop, D. R.; Abbatt, J. P. D.

    2014-12-01

    The soot-particle aerosol mass spectrometer (SP-AMS) uses an intra-cavity infrared laser to vaporize refractory black carbon (rBC) containing particles, making the particle beam-laser beam overlap critical in determining the collection efficiency (CE) for rBC and associated non-refractory particulate matter (NR-PM). This work evaluates the ability of the SP-AMS to quantify rBC and NR-PM mass in internally mixed particles with different thicknesses of organic coating. Using apparent relative ionization efficiencies for uncoated and thickly coated rBC particles, we report measurements of SP-AMS sensitivity to NR-PM and rBC, for Regal Black, the recommended particulate calibration material. Beam width probe (BWP) measurements are used to illustrate an increase in sensitivity for highly coated particles due to narrowing of the particle beam, which enhances the CE of the SP-AMS by increasing the laser beam-particle beam overlap. Assuming complete overlap for thick coatings, we estimate CE for bare Regal Black particles of 0.6 ± 0.1, which suggests that previously measured SP-AMS sensitivities to Regal Black were underestimated by up to a factor of 2. The efficacy of the BWP measurements is highlighted by studies at a busy road in downtown Toronto and at a non-roadside location, which show particle beam widths similar to, but greater than that of bare Regal Black and coated Regal Black, respectively. Further BWP measurements at field locations will help to constrain the range of CE for fresh and aged rBC-containing particles. The ability of the SP-AMS to quantitatively assess the composition of internally mixed particles is validated through measurements of laboratory-generated organic coated particles, which demonstrate that the SP-AMS can quantify rBC and NR-PM over a wide range of particle compositions and rBC core sizes.

  17. Optimized method for black carbon analysis in ice and snow using the Single Particle Soot Photometer

    Directory of Open Access Journals (Sweden)

    I. A. Wendl

    2014-03-01

    Full Text Available In this study we attempt to optimize the method for measuring black carbon (BC in snow and ice using a single particle soot photometer (SP2. Beside the previously applied ultrasonic (CETAC and Collison-type nebulizers we introduce a jet (APEX-Q nebulizer to aerosolize the aqueous sample for SP2 analysis. Both CETAC and APEX-Q require small sample volumes (few milliliters which makes them suitable for ice core analysis. The APEX-Q shows the least size-dependent nebulizing efficiency in the BC particle diameter range of 100–1000 nm. The CETAC has the advantage that air and liquid flows can be monitored continuously. All nebulizer-types require a calibration with BC standards for the determination of the BC mass concentration in unknown aqueous samples. We found Aquadag to be a suitable material for preparing calibration standards. Further, we studied the influence of different treatments for fresh discrete snow and ice samples as well as the effect of storage. The results show that samples are best kept frozen until analysis. Once melted, they should be sonicated for 25 min, immediately analyzed while being stirred and not be refrozen.

  18. Effect of Initial Aluminum Alloy Particle Size on the Damage of Carbon Nanotubes during Ball Milling

    Directory of Open Access Journals (Sweden)

    Xian Zhu

    2016-03-01

    Full Text Available Damage to carbon nanotubes (CNTs during the fabrication process of CNT reinforced composites has great influence on their mechanical properties. In this study, the 2014 Al with powder sizes of 20, 9 and 5 μm was selected to study the effect of initial particle size on the damage to carbon nanotubes (CNTs during ball milling. The result shows that for CNTs in the ball milled CNT/Al (with powder size of 20 and 9 μm mixtures, the intensity ratio of the D band and the G band (ID/IG first increased and then reached a plateau, mainly because most of the CNTs are embedded, to a certain extent, in the aluminum powder after milling, which could protect the CNTs from damage during further milling. While for CNTs in the ball milled CNT/Al (with powder size of 5 μm mixture, the ID/IG ratio continues to climb from 1.31 to 2.33 with time, indicating continuous damage to the CNTs occurs during the milling. Differential scanning calorimetry (DSC analysis demonstrates that the chemical instability increased with an increase in the damage level of CNTs, resulting in the formation of aluminum carbide (Al4C3 at a lower temperature before the melting of aluminum, which is detrimental to their mechanical properties.

  19. The transcriptional repressor ZBP-89 and the lack of Sp1/Sp3, c-Jun, and Stat3 are important for the down-regulation of the vimentin gene during C2C12 myogenesis

    OpenAIRE

    Salmon, Morgan; Zehner, Zendra E.

    2009-01-01

    Currently, considerable information is available about how muscle-specific genes are activated during myogenesis, yet little is known about how non-muscle genes are down-regulated. The intermediate filament protein vimentin is known to be “turned off” during myogenesis to be replaced by desmin, the muscle-specific intermediate filament protein. Here, we demonstrate that vimentin down-regulation is the result of the combined effect of several transcription factors. Levels of the positive activ...

  20. Escin Ia suppresses the metastasis of triple-negative breast cancer by inhibiting epithelial-mesenchymal transition via down-regulating LOXL2 expression.

    Science.gov (United States)

    Wang, Yuhui; Xu, Xiaotian; Zhao, Peng; Tong, Bei; Wei, Zhifeng; Dai, Yue

    2016-04-26

    The saponin fraction of Aesculus chinensis Bunge fruits (SFAC) could inhibit the invasion and migration of MDA-MB-231 cells. Among which, escin Ia showed more potent inhibition of the invasion than other five main saponin constituents. It selectively reduced the expression of LOXL2 mRNA and promoted the expression of E-cadherin mRNA, and prevented the EMT process of MDA-MB-231 cells and TNF-α/TGF-β-stimulated MCF-7 cells. Moreover, it reduced the LOXL2 level in MDA-MB-231 cells but not in MCF-7 cells. When MCF-7 cells were stimulated with TNF-α/TGF-β, transfected with LOXL2 or treated with hypoxia, escin Ia down-regulated the level of LOXL2 in MCF-7 cells. Meanwhile, escin Ia suppressed the EMT process in LOXL2-transfected or hypoxia-treated MCF-7 cells. Of interest, escin Ia did not alter the level of HIF-1α in hypoxia-induced MCF-7 cells. In TNBC xenograft mice, the metastasis and EMT of MDA-MB-231 cells were suppressed by escin Ia. In conclusion, escin Ia was the main active ingredient of SFAC for the anti-TNBC metastasis activity, and its action mechanisms involved inhibition of EMT process by down-regulating LOXL2 expression.

  1. Down-regulation of IKKβ expression in glioma-infiltrating microglia/macrophages is associated with defective inflammatory/immune gene responses in glioblastoma.

    Science.gov (United States)

    Mieczkowski, Jakub; Kocyk, Marta; Nauman, Pawel; Gabrusiewicz, Konrad; Sielska, Małgorzata; Przanowski, Piotr; Maleszewska, Marta; Rajan, Wenson D; Pszczolkowska, Dominika; Tykocki, Tomasz; Grajkowska, Wieslawa; Kotulska, Katarzyna; Roszkowski, Marcin; Kostkiewicz, Boguslaw; Kaminska, Bozena

    2015-10-20

    Glioblastoma (GBM) is an aggressive malignancy associated with profound host immunosuppression. Microglia and macrophages infiltrating GBM acquire the pro-tumorigenic, M2 phenotype and support tumor invasion, proliferation, survival, angiogenesis and block immune responses both locally and systematically. Mechanisms responsible for immunological deficits in GBM patients are poorly understood. We analyzed immune/inflammatory gene expression in five datasets of low and high grade gliomas, and performed Gene Ontology and signaling pathway analyses to identify defective transcriptional responses. The expression of many immune/inflammatory response and TLR signaling pathway genes was reduced in high grade gliomas compared to low grade gliomas. In particular, we found the reduced expression of the IKBKB, a gene coding for IKKβ, which phosphorylates IκB proteins and represents a convergence point for most signal transduction pathways leading to NFκB activation. The reduced IKBKB expression and IKKβ levels in GBM tissues were demonstrated by qPCR, Western blotting and immunohistochemistry. The IKKβ expression was down-regulated in microglia/macrophages infiltrating glioblastoma. NFκB activation, prominent in microglia/macrophages infiltrating low grade gliomas, was reduced in microglia/macrophages in glioblastoma tissues. Down-regulation of IKBKB expression and NFκB signaling in microglia/macrophages infiltrating glioblastoma correlates with defective expression of immune/inflammatory genes and M2 polarization that may result in the global impairment of anti-tumor immune responses in glioblastoma.

  2. Curcumin ameliorates neuropathic pain by down-regulating spinal IL-1β via suppressing astroglial NALP1 inflammasome and JAK2-STAT3 signalling

    Science.gov (United States)

    Liu, Shenbin; Li, Qian; Zhang, Meng-Ting; Mao-Ying, Qi-Liang; Hu, Lang-Yue; Wu, Gen-Cheng; Mi, Wen-Li; Wang, Yan-Qing

    2016-01-01

    Curcumin has been shown to possess strong anti-inflammatory activity in many diseases. It has been demonstrated that the janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 (STAT3) cascade and the NAcht leucine-rich-repeat protein 1 (NALP1) inflammasome are important for the synthesis of Pro-Interleukin (IL)-1β and the processing of the inactive protein to its mature form, which plays an active role in the pathogenesis of neuropathic pain. The present study showed that repeated intraperitoneal injection of curcumin ameliorated SNI-induced mechanical and cold allodynia in a dose-dependent manner and inhibited the elevation of spinal mature IL-1β protein levels. Additionally, repeated curcumin treatment significantly inhibited the aggregation of the NALP1 inflammasome and the activation of the JAK2-STAT3 cascade in spinal astrocytes. Furthermore, the genetic down-regulation of NALP1 inflammasome activation by NALP1 siRNA and the pharmacological inhibition of the JAK2-STAT3 cascade by AG490 markedly inhibited IL-1β maturation and Pro-IL-1β synthesis, respectively, and reduced SNI-induced pain hypersensitivity. Our results suggest that curcumin attenuated neuropathic pain and down-regulated the production of spinal mature IL-1β by inhibiting the aggregation of NALP1 inflammasome and the activation of the JAK2-STAT3 cascade in astrocytes. PMID:27381056

  3. Osteoprotegerin inhibits calcification of vascular smooth muscle cell via down regulation of the Notch1-RBP-Jκ/Msx2 signaling pathway.

    Directory of Open Access Journals (Sweden)

    Shaoqiong Zhou

    Full Text Available OBJECTIVE: Vascular calcification is a common pathobiological process which occurs among the elder population and in patients with diabetes and chronic kidney disease. Osteoprotegerin, a secreted glycoprotein that regulates bone mass, has recently emerged as an important regulator of the development of vascular calcification. However, the mechanism is not fully understood. The purpose of this study is to explore novel signaling mechanisms of osteoprotegerin in the osteoblastic differentiation in rat aortic vascular smooth muscle cells (VSMCs. METHODS AND RESULTS: VSMCs were isolated from thoracic aorta of Sprague Dawley rats. Osteoblastic differentiation of VSMCs was induced by an osteogenic medium. We confirmed by Von Kossa staining and direct cellular calcium measurement that mineralization was significantly increased in VSMCs cultured in osteogenic medium; consistent with an enhanced alkaline phosphatase activity. This osteoblastic differentiation in VSMCs was significantly reduced by the addition of osteoprotegerin in a dose responsive manner. Moreover, we identified, by real-time qPCR and western blotting, that expression of Notch1 and RBP-Jκ were significantly up-regulated in VSMCs cultured in osteogenic medium at both the mRNA and protein levels, these effects were dose-dependently abolished by the treatment of osteoprotegerin. Furthermore, we identified that Msx2, a downstream target of the Notch1/RBP-Jκ signaling, was markedly down-regulated by the treatment of osteoprotegerin. CONCLUSION: Osteoprotegerin inhibits vascular calcification through the down regulation of the Notch1-RBP-Jκ signaling pathway.

  4. BAFF induces spleen CD4+ T cell proliferation by down-regulating phosphorylation of FOXO3A and activates cyclin D2 and D3 expression

    International Nuclear Information System (INIS)

    Highlights: ► Firstly analyze the mechanism of BAFF and anti-CD3 co-stimulation on purified mouse splenic CD4+ T cells. ► Carrying out siRNA technology to study FOXO3A protein function. ► Helpful to understand the T cell especially CD4+ T cell‘s role in immunological reaction. -- Abstract: The TNF ligand family member “B cell-activating factor belonging to the TNF family” (BAFF, also called BLyS, TALL-1, zTNF-4, and THANK) is an important survival factor for B and T cells. In this study, we show that BAFF is able to induce CD4+ spleen T cell proliferation when co-stimulated with anti-CD3. Expression of phosphorylated FOXO3A was notably down-regulated and cyclins D2 and D3 were up-regulated and higher in the CD4+ T cells when treated with BAFF and anti-CD3, as assessed by Western blotting. Furthermore, after FOXO3A was knocked down, expression of cyclin D1 was unchanged, compared with control group levels, but the expression of cyclins D2 and D3 increased, compared with the control group. In conclusion, our results suggest that BAFF induced CD4+ spleen T cell proliferation by down-regulating the phosphorylation of FOXO3A and then activating cyclin D2 and D3 expression, leading to CD4+ T cell proliferation.

  5. The candidate tumor suppressor CST6 alters the gene expression profile of human breast carcinoma cells: Down-regulation of the potent mitogenic, motogenic, and angiogenic factor autotaxin

    International Nuclear Information System (INIS)

    We recently coined CST6 as a novel candidate tumor suppressor gene for breast cancer. CST6 indeed is expressed in the normal human breast epithelium, but little or not at all in breast carcinomas and breast cancer cell lines. Moreover, ectopic expression of CST6 in human breast cancer cells suppressed cell proliferation, migration, invasion, and orthotopic tumor growth. To obtain insights into the molecular mechanism by which CST6 exhibits its pleiotropic effects on tumor cells, we compared global gene expression profiles in mock- and CST6-transfected human MDA-MB-435S cells. Out of 12,625 transcript species, 61 showed altered expression. These included genes for extracellular matrix components, cytokines, kinases, and phosphatases, as well as several key transcription factors. TaqMan PCR assays were used to confirm the microarray data for 7 out of 11 genes. One down-regulated gene product, secreted autotaxin/lyso-phospholipase D, was of particular interest because its down-regulation by CST6 could explain most of CST6's effect on the breast cancer cells. This study thus provides First evidence that CST6 plays a role in the modulation of genes, particularly, genes that are highly relevant to breast cancer progression

  6. Asclepiasterol, a novel C21 steroidal glycoside derived from Asclepias curassavica, reverses tumor multidrug resistance by down-regulating P-glycoprotein expression.

    Science.gov (United States)

    Yuan, Wei-Qi; Zhang, Rong-Rong; Wang, Jun; Ma, Yan; Li, Wen-Xue; Jiang, Ren-Wang; Cai, Shao-Hui

    2016-05-24

    Multidrug resistance (MDR) mediated by P-glycoprotein (P-gp) is a major cause of cancer therapy failure. In this study, we identified a novel C21 steroidal glycoside, asclepiasterol, capable of reversing P-gp-mediated MDR. Asclepiasterol (2.5 and 5.0μM) enhanced the cytotoxity of P-gp substrate anticancer drugs in MCF-7/ADR and HepG-2/ADM cells. MDR cells were more responsive to paclitaxel in the presence of asclepiasterol, and colony formation of MDR cells was only reduced upon treatment with a combination of asclepiasterol and doxorubicin. Consistent with these findings, asclepiasterol treatment increased the intracellular accumulation of doxorubicin and rhodamine 123 (Rh123) in MDR cells. Asclepiasterol decreased expression of P-gp protein without stimulating or suppressing MDR1 mRNA levels. Asclepiasterol-mediated P-gp suppression caused inhibition of ERK1/2 phosphorylation in two MDR cell types, and EGF, an activator of the MAPK/ERK pathway, reversed the P-gp down-regulation, implicating the MAPK/ERK pathway in asclepiasterol-mediated P-gp down-regulation. These results suggest that asclepiasterol could be developed as a modulator for reversing P-gp-mediated MDR in P-gp-overexpressing cancer variants. PMID:27129170

  7. Thrombomodulin reduces tumorigenic and metastatic potential of lung cancer cells by up-regulation of E-cadherin and down-regulation of N-cadherin expression.

    Science.gov (United States)

    Zheng, Nana; Huo, Zihe; Zhang, Bin; Meng, Mei; Cao, Zhifei; Wang, Zhiwei; Zhou, Quansheng

    2016-08-01

    Thrombomodulin (TM) is an endothelial cell membrane protein and plays critical roles in anti-thrombosis, anti-inflammation, vascular endothelial protection, and is traditionally regarded as a "vascular protection god". In recent years, although TM has been reported to be down-regulated in a variety of malignant tumors including lung cancer, the role and mechanism of TM in lung cancer are enigmatic. In this study, we found that induction of TM overexpression by cholesterol-reducing drug atorvastatin significantly diminished the tumorigenic capability of the lung cancer cells. Moreover, we demonstrated that TM overexpression caused G0/G1 phase arrest and markedly reduced the colony forming capability of the cells. Furthermore, overexpression of TM inhibited cell migration and invasion. Consistently, depletion of TM promoted cell growth, reduced the cell population at the G0/G1 phase, and enhanced cell migratory ability. Mechanistic study revealed that TM up-regulated E-cadherin but down-regulated N-cadherin expression, resulting in reversal of epithelial-mesenchymal transition (EMT) in the lung cancer cells. Moreover, silencing TM expression led to decreased E-cadherin and increased N-cadherin. Taken together, our study suggests that TM functions as a tumor suppressive protein, providing a conceptual framework for inducing TM overexpression as a sensible strategy and approach for novel anti-lung cancer drug discovery. PMID:27223053

  8. Localized Down-regulation of P-glycoprotein by Focused Ultrasound and Microbubbles induced Blood-Brain Barrier Disruption in Rat Brain

    Science.gov (United States)

    Cho, Hongseok; Lee, Hwa-Youn; Han, Mun; Choi, Jong-Ryul; Ahn, Sanghyun; Lee, Taekwan; Chang, Yongmin; Park, Juyoung

    2016-08-01

    Multi-drug resistant efflux transporters found in Blood-Brain Barrier (BBB) acts as a functional barrier, by pumping out most of the drugs into the blood. Previous studies showed focused ultrasound (FUS) induced microbubble oscillation can disrupt the BBB by loosening the tight junctions in the brain endothelial cells; however, no study was performed to investigate its impact on the functional barrier of the BBB. In this study, the BBB in rat brains were disrupted using the MRI guided FUS and microbubbles. The immunofluorescence study evaluated the expression of the P-glycoprotein (P-gp), the most dominant multi-drug resistant protein found in the BBB. Intensity of the P-gp expression at the BBB disruption (BBBD) regions was significantly reduced (63.2 ± 18.4%) compared to the control area. The magnitude of the BBBD and the level of the P-gp down-regulation were significantly correlated. Both the immunofluorescence and histologic analysis at the BBBD regions revealed no apparent damage in the brain endothelial cells. The results demonstrate that the FUS and microbubbles can induce a localized down-regulation of P-gp expression in rat brain. The study suggests a clinically translation of this method to treat neural diseases through targeted delivery of the wide ranges of brain disorder related drugs.

  9. Prostaglandin EP2 receptor signaling protects human trabecular meshwork cells from apoptosis induced by ER stress through down-regulation of p53.

    Science.gov (United States)

    Kalouche, Georges; Boucher, Céline; Coste, Annick; Debussche, Laurent; Orsini, Cécile; Baudouin, Christophe; Debeir, Thomas; Vigé, Xavier; Rostène, William

    2016-09-01

    E-prostanoid receptor subtype 2 (EP2) agonists are currently under clinical development as hypotensive agents for the treatment of ocular hypertension. However, the effects of EP2 receptor agonists on trabecular meshwork (TM) alterations leading to primary open-angle glaucoma (POAG) are still unknown. Here, we evaluated whether EP2 receptor activation exhibits protective functions on TM cell death induced by endoplasmic reticulum (ER) stress. We show that the EP2 receptor agonist butaprost protects TM cell death mediated by the ER stress inducer tunicamycin through a cyclic AMP (cAMP)-dependent mechanism, but independent of the classical cAMP sensors, protein kinase A and exchange proteins activated by cAMP. The ER stress-induced intrinsic apoptosis inhibited by the EP2 receptor agonist was correlated with a decreased accumulation of the cellular stress sensor p53. In addition, p53 down-regulation was associated with inhibition of its transcriptional activity, which led to decreased expression of the pro-apoptotic p53-upregulated modulator of apoptosis (PUMA). The stabilization of p53 by nutlin-3a abolished butaprost-mediated cell death protection. In conclusion, we showed that EP2 receptor activation protects against ER stress-dependent mitochondrial apoptosis through down-regulation of p53. The specific inhibition of this pathway could reduce TM alterations observed in POAG patients. PMID:27321910

  10. Down regulation of pRb in cultures of avian neuroretina cells promotes proliferation of reactive Müller-like cells and emergence of retinal stem/progenitors.

    Science.gov (United States)

    Marx, Maria; Lebuhotel, Céline; Laugier, Danielle; Chapelle, Audrey; Calothy, Georges; Saule, Simon

    2010-06-01

    The aim of this work was to define the role of pRb depletion in the proliferation and differentiation of avian retinoblasts in vitro. For this purpose vectors expressing pRb short hairpin RNA were used to deplete pRb in cultures of avian neuroretinal cells. Down regulation of pRb was observed by Western blot and quantification of nuclear pRb. Cell proliferation and differentiation were studied following BrdU labeling and immunostaining. Transfection significantly down-regulated pRb in neuroretinal cells. Long-term effect of pRb depletion mainly induced proliferation of epithelial-like cells that expressed markers of reactive Müller glial cells. A minority of these cells that survived passaging could be maintained as neurosphere-like aggregates with low pRb, not observed in control cultures. BrdU labeling followed by a two week chase showed the presence of cells still remained labelled, indicating low cell cycling. Under appropriate conditions, these aggregates differentiate in precursors of amacrine interneurons shown by the expression of AP2, in absence of the photoreceptors marker visinin and the late neuronal marker MAP2. Taken together these data show that decrease pRb level in cultures of avian neuroretinal cells promotes the emergence and proliferation of stem cell/progenitors from reactive-like Muller cells.

  11. Protein-bound Polysaccharide-K Inhibits Hedgehog Signaling Through Down-regulation of MAML3 and RBPJ Transcription Under Hypoxia, Suppressing the Malignant Phenotype in Pancreatic Cancer.

    Science.gov (United States)

    Yamasaki, Akio; Onishi, Hideya; Imaizumi, Akira; Kawamoto, Makoto; Fujimura, Akiko; Oyama, Yasuhiro; Katano, Mitsuo

    2016-08-01

    Hedgehog signaling is activated in pancreatic cancer and could be a therapeutic target. We previously demonstrated that recombination signal binding protein for immunoglobulin-kappa-J region (RBPJ) and mastermind-like 3 (MAML3) contribute to the hypoxia-induced up-regulation of Smoothened (SMO) transcription. We have also shown that protein-bound polysaccharide-K (PSK) could be effective for refractory pancreatic cancer that down-regulates SMO transcription under hypoxia. In this study, we evaluated whether the anticancer mechanism of PSK involves inhibiting RBPJ and MAML3 expression under hypoxia. PSK reduced SMO, MAML3 and RBPJ expression in pancreatic cancer cells under hypoxia. PSK also blocked RBPJ-induced invasiveness under hypoxia by inhibiting matrix metalloproteinase expression. Lastly, we showed that PSK attenuated RBPJ-induced proliferation both in vitro and in vivo. These results suggest that PSK suppresses Hedgehog signaling through down-regulation of MAML3 and RBPJ transcription under hypoxia, inhibiting the induction of a malignant phenotype in pancreatic cancer. Our results may lead to development of new treatments for refractory pancreatic cancer using PSK as a Hedgehog inhibitor. PMID:27466498

  12. pH-responsive artemisinin derivatives and lipid nanoparticle formulations inhibit growth of breast cancer cells in vitro and induce down-regulation of HER family members.

    Directory of Open Access Journals (Sweden)

    Yitong J Zhang

    Full Text Available Artemisinin (ART dimers show potent anti-proliferative activities against breast cancer cells. To facilitate their clinical development, novel pH-responsive artemisinin dimers were synthesized for liposomal nanoparticle formulations. A new ART dimer was designed to become increasingly water-soluble as pH declines. The new artemisinin dimer piperazine derivatives (ADPs remained tightly associated with liposomal nanoparticles (NPs at neutral pH but were efficiently released at acidic pH's that are known to exist within solid tumors and organelles such as endosomes and lysosomes. ADPs incorporated into nanoparticles down regulated the anti-apoptotic protein, survivin, and cyclin D1 when incubated at low concentrations with breast cancer cell lines. We demonstrate for the first time, for any ART derivative, that ADP NPs can down regulate the oncogenic protein HER2, and its counterpart, HER3 in a HER2+ cell line. We also show that the wild type epidermal growth factor receptor (EGFR or HER1 declines in a triple negative breast cancer (TNBC cell line in response to ADP NPs. The declines in these proteins are achieved at concentrations of NP109 at or below 1 µM. Furthermore, the new artemisinin derivatives showed improved cell-proliferation inhibition effects compared to known dimer derivatives.

  13. Localized Down-regulation of P-glycoprotein by Focused Ultrasound and Microbubbles induced Blood-Brain Barrier Disruption in Rat Brain

    Science.gov (United States)

    Cho, HongSeok; Lee, Hwa-Youn; Han, Mun; Choi, Jong-ryul; Ahn, Sanghyun; Lee, Taekwan; Chang, Yongmin; Park, Juyoung

    2016-01-01

    Multi-drug resistant efflux transporters found in Blood-Brain Barrier (BBB) acts as a functional barrier, by pumping out most of the drugs into the blood. Previous studies showed focused ultrasound (FUS) induced microbubble oscillation can disrupt the BBB by loosening the tight junctions in the brain endothelial cells; however, no study was performed to investigate its impact on the functional barrier of the BBB. In this study, the BBB in rat brains were disrupted using the MRI guided FUS and micr