WorldWideScience

Sample records for carbon particles down-regulate

  1. Carbon particles

    Science.gov (United States)

    Hunt, Arlon J.

    1984-01-01

    A method and apparatus whereby small carbon particles are made by pyrolysis of a mixture of acetylene carried in argon. The mixture is injected through a nozzle into a heated tube. A small amount of air is added to the mixture. In order to prevent carbon build-up at the nozzle, the nozzle tip is externally cooled. The tube is also elongated sufficiently to assure efficient pyrolysis at the desired flow rates. A key feature of the method is that the acetylene and argon, for example, are premixed in a dilute ratio, and such mixture is injected while cool to minimize the agglomeration of the particles, which produces carbon particles with desired optical properties for use as a solar radiant heat absorber.

  2. 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

  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. 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

  6. 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.

  7. 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.

  8. 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.

  9. DMBT1 expression is down-regulated in breast cancer

    DEFF Research Database (Denmark)

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

    2004-01-01

    expression was down-regulated in the cancerous lesions compared to the normal and/or hyperplastic epithelium adjacent to carcinomas (3/55 positive carcinomas versus 33/42 positive normal/hyperplastic epithelia; p = 0.0001). In 72% of cases RT-PCR confirmed immunohistochemical results. Most of normal 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...

  10. 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...

  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. 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

  13. TCR down-regulation controls T cell homeostasis

    DEFF Research Database (Denmark)

    Boding, Lasse; Bonefeld, Charlotte Menné; Nielsen, Bodil L;

    2009-01-01

    TCR and cytokine receptor signaling play key roles in the complex homeostatic mechanisms that maintain a relative stable number of T cells throughout life. Despite the homeostatic mechanisms, a slow decline in naive T cells is typically observed with age. The CD3gamma di-leucine-based motif...... was caused by the combination of reduced thymic output, decreased T cell apoptosis, and increased transition of naive T cells to memory T cells. Experiments with bone marrow chimeric mice confirmed that the CD3gammaLLAA mutation exerted a T cell intrinsic effect on T cell homeostasis that resulted in...... controls TCR down-regulation and plays a central role in fine-tuning TCR expression and signaling in T cells. In this study, we show that the age-associated decline of naive T cells is strongly accelerated in CD3gammaLLAA knock-in mice homozygous for a double leucine to alanine mutation in the CD3gamma di...

  14. 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

  15. Down-Regulation of Cell Surface Receptors Is Modulated by Polar Residues within the Transmembrane Domain

    OpenAIRE

    Zaliauskiene, Lolita; Kang, Sunghyun; Brouillette, Christie G; Lebowitz, Jacob; Arani, Ramin B; Collawn, James F.

    2000-01-01

    How recycling receptors are segregated from down-regulated receptors in the endosome is unknown. In previous studies, we demonstrated that substitutions in the transferrin receptor (TR) transmembrane domain (TM) convert the protein from an efficiently recycling receptor to one that is rapidly down regulated. In this study, we demonstrate that the “signal” within the TM necessary and sufficient for down-regulation is Thr11Gln17Thr19 (numbering in TM). Transplant...

  16. 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.

  17. 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....

  18. 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...

  19. 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

  20. Down-Regulation of Cell Surface Receptors Is Modulated by Polar Residues within the Transmembrane Domain

    Science.gov (United States)

    Zaliauskiene, Lolita; Kang, Sunghyun; Brouillette, Christie G.; Lebowitz, Jacob; Arani, Ramin B.; Collawn, James F.

    2000-01-01

    How recycling receptors are segregated from down-regulated receptors in the endosome is unknown. In previous studies, we demonstrated that substitutions in the transferrin receptor (TR) transmembrane domain (TM) convert the protein from an efficiently recycling receptor to one that is rapidly down regulated. In this study, we demonstrate that the “signal” within the TM necessary and sufficient for down-regulation is Thr11Gln17Thr19 (numbering in TM). Transplantation of these polar residues into the wild-type TR promotes receptor down-regulation that can be demonstrated by changes in protein half-life and in receptor recycling. Surprisingly, this modification dramatically increases the TR internalization rate as well (∼79% increase). Sucrose gradient centrifugation and cross-linking studies reveal that propensity of the receptors to self-associate correlates with down-regulation. Interestingly, a number of cell surface proteins that contain TM polar residues are known to be efficiently down-regulated, whereas recycling receptors for low-density lipoprotein and transferrin conspicuously lack these residues. Our data, therefore, suggest a simple model in which specific residues within the TM sequences dramatically influence the fate of membrane proteins after endocytosis, providing an alternative signal for down-regulation of receptor complexes to the well-characterized cytoplasmic tail targeting signals. PMID:10930460

  1. 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...

  2. Carbon Fiber Damage in Particle Beam

    CERN Document Server

    Dehning, B; Kroyer, T; Meyer, M; Sapinski, M

    2011-01-01

    Carbon fibers are commonly used as moving targets in beam wire scanners. The heating of the fiber due to energy loss of the particles travelling through is simulated with Geant4. The heating induced by the beam electromagnetic field is estimated with ANSYS. The heat transfer and sublimation processes are modelled. Due to the model nonlinearity, a numerical approach based on discretization of the wire movement is used to solve it for particular beams. Radiation damage to the fiber is estimated with SRIM. The model is tested with available SPS and LEP data and a dedicated damage test on the SPS beam is performed followed by a post-mortem analysis of the wire remnants. Predictions for the LHC beams are made.

  3. 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

  4. 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...

  5. 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...

  6. Proteasome involvement in agonist-induced down-regulation of mu and delta opioid receptors.

    Science.gov (United States)

    Chaturvedi, K; Bandari, P; Chinen, N; Howells, R D

    2001-04-13

    This study investigated the mechanism of agonist-induced opioid receptor down-regulation. Incubation of HEK 293 cells expressing FLAG-tagged delta and mu receptors with agonists caused a time-dependent decrease in opioid receptor levels assayed by immunoblotting. Pulse-chase experiments using [(35)S]methionine metabolic labeling indicated that the turnover rate of delta receptors was accelerated 5-fold following agonist stimulation. Inactivation of functional G(i) and G(o) proteins by pertussis toxin-attenuated down-regulation of the mu opioid receptor, while down-regulation of the delta opioid receptor was unaffected. Pretreatment of cells with inhibitors of lysosomal proteases, calpain, and caspases had little effect on mu and delta opioid receptor down-regulation. In marked contrast, pretreatment with proteasome inhibitors attenuated agonist-induced mu and delta receptor down-regulation. In addition, incubation of cells with proteasome inhibitors in the absence of agonists increased steady-state mu and delta opioid receptor levels. Immunoprecipitation of mu and delta opioid receptors followed by immunoblotting with ubiquitin antibodies suggested that preincubation with proteasome inhibitors promoted accumulation of polyubiquitinated receptors. These data provide evidence that the ubiquitin/proteasome pathway plays a role in agonist-induced down-regulation and basal turnover of opioid receptors. PMID:11152677

  7. Interaction forces between waterborne bacteria and activated carbon particles.

    Science.gov (United States)

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

    2008-06-01

    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 positively charged, mesoporous wood-based carbons, as well as with a microporous coconut carbon. To this end, we glued carbon particles to the cantilever of an atomic force microscope and measured the interaction forces upon approach and retraction of thus made tips. Waterborne Raoultella terrigena and Escherichia coli adhered weakly (1-2 nN) to different activated carbon particles, and the main difference between the activated carbons was the percentage of curves with attractive sites revealed upon traversing of a carbon particle through the bacterial EPS layer. The percentage of curves showing adhesion forces upon retraction varied between 21% and 69%, and was highest for R. terrigena with positively charged carbon (66%) and a coconut carbon (69%). Macroscopic bacterial removal by the mesoporous carbon particles increased with increasing percentages of attractive sites revealed upon traversing a carbon particle through the outer bacterial surface layer. PMID:18405910

  8. 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

  9. 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

  10. 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.

  11. 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...

  12. Structural Characterization of Lignin in Wild-type versus COMT Down-regulated Switchgrass

    Directory of Open Access Journals (Sweden)

    ArthurRagauskas

    2014-01-01

    Full Text Available This study examined the chemical structural characteristics of cellulolytic enzyme lignin isolated from switchgrass focusing on comparisons between wild-type control and caffeic acid 3-O-methyltransferase (COMT down-regulated transgenic line. Nuclear magnetic resonance (NMR techniques including 13C, 31P, and two-dimensional 13C-1H heteronuclear single quantum coherence (HSQC as well as gel permeation chromatography (GPC were employed. Compared to the wild-type, the COMT down-regulated transgenic switchgrass lignin demonstrated a decrease in syringyl (S: guaiacyl (G ratio and p-coumarate:ferulate ratio, an increase in relative abundance of phenylcoumaran unit, and a comparable content of total free phenolic OH groups along with formation of benzodioxane unit. In addition, COMT down-regulation had no significant effects on the lignin molecular weights during its biosynthesis process.

  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

    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...... expressed mRNAs demonstrated an enrichment of seed-sites among up-regulated transcripts encoding proteins implicated in thyroid tumourigenesis. This was substantiated by the demonstration that pre-miR-199b reduced proliferation when added to cultured follicular thyroid carcinoma cells. The down-regulated mi......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. Serotonin-induced down-regulation of cell surface serotonin transporter

    DEFF Research Database (Denmark)

    Jørgensen, Trine Nygaard; Christensen, Peter Møller; Gether, Ulrik

    2014-01-01

    The serotonin transporter (SERT) terminates serotonergic signaling and enables refilling of synaptic vesicles by mediating reuptake of serotonin (5-HT) released into the synaptic cleft. The molecular and cellular mechanisms controlling SERT activity and surface expression are not fully understood....... Here we demonstrate that the substrate 5-HT itself causes acute down-regulation of SERT cell surface expression. To assess surface SERT expression by ELISA, we used a SERT variant (TacSERT) where the N-terminus of SERT was fused to the intracellular tail of the extracellularly FLAG-tagged single...... neurons, indicting that endogenous cell-surface resident SERT likewise is down-regulated in the presence of substrate....

  15. 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

  16. 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.

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

    DEFF Research Database (Denmark)

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

    2012-01-01

    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...

  18. 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...

  19. Carbon-Supported Iron Oxide Particles

    DEFF Research Database (Denmark)

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

    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...

  20. Dielectrophoresis in particle confinement: Aligned carbon particles in polymer matrix below percolation threshold

    Science.gov (United States)

    Knaapila, M.; Høyer, H.; Helgesen, G.

    2014-09-01

    We review preparation and properties of confined, aligned string-like particle assemblies formed by dielectrophoresis under alternating electric fields. Particular attention is placed on carbon particles aligned in the oligomer matrix. In these systems the particle fraction is low, below the isotropic percolation threshold. The matrix is polymerized after alignment, which locks the aligned strings in place. Application examples are discussed including particle separation, conductivity enhancement and piezoresistive sensors.

  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. 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

  4. Preparation of porous carbon particle with shell/core structure

    Directory of Open Access Journals (Sweden)

    2007-05-01

    Full Text Available Porous carbon particles with a shell/core structure have been prepared successfully by controlled precipitation of the polymer from droplets of oil-in-water emulsion, followed by curing and carbonization. The droplets of the oil phase are composed of phenolic resin (PFR, a good solvent (ethyl acetate and porogen (Poly(methyl methacrylate, PMMA. The microstructure was characterized in detail by scanning electron microscopy (SEM, transmission electron microscopy (TEM, nitrogen adsorption, and thermo gravimetric analysis (TGA. The obtained carbon particles have a capsular structure with a microporous carbon shell and a mesoporous carbon core. The BET surface area and porous volume are calculated to be 499 m2g-1 and 0.56 cm3g-1, respectively. The effects of the amount of porogen (PMMA, co-solvent (acetone and surfactant on the resultant structure were studied in detail.

  5. 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.

  6. 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.

  7. Down-regulation of the desmosomal cadherin desmocollin 3 in human breast cancer.

    Science.gov (United States)

    Klus, G T; Rokaeus, N; Bittner, M L; Chen, Y; Korz, D M; Sukumar, S; Schick, A; Szallasi, Z

    2001-07-01

    In previous studies using cDNA microarray analysis, we have identified an expressed sequence tag which is consistently down-regulated in six human breast tumor cell lines. In the current study, we have determined this tag to be part of the mRNA sequence of human desmocollin 3, a member of the cadherin superfamily of proteins and an integral component of desmosomes. Desmosomes are sites of adhesion between adjacent cells in layers of epithelia, as well as in some non-epithelial tissues, and play an important role in the maintenance of tissue structure. Northern analysis, quantitative real-time polymerase chain reaction assay and Western blot analysis showed that desmocollin 3 is present in normal and immortalized human mammary epithelial cells, but consistently exhibits a significant, and often complete, down-regulation in breast cancer cell lines and primary breast tumors, both at the mRNA and protein levels. PMID:11408939

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

    International Nuclear Information System (INIS)

    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

  9. 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.

  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. 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...

  12. 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...

  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. 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...

  15. GATA3 in the urinary bladder: suppression of neoplastic transformation and down-regulation by androgens

    OpenAIRE

    Li, Yi; Ishiguro, Hitoshi; Kawahara, Takashi; Miyamoto, Yurina; Izumi, Koji; Miyamoto, Hiroshi

    2014-01-01

    Recent evidence suggests the involvement of sex hormone receptors in bladder cancer initiation, while precise functions of androgens and estrogens in the carcinogenesis step remain poorly understood. We recently found down-regulation of GATA3, a zinc-finger transcription factor and a new urothelial marker, in bladder cancer, which also correlated with expression status of androgen receptor (AR) and estrogen receptors (ERs). We here assessed whether GATA3 acted as a suppressor of bladder tumor...

  16. 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

  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. PMID:27178152

  18. 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

  19. 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.

  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. Retention and clearance of inhaled submicron carbon black particles.

    Science.gov (United States)

    Strom, K A; Johnson, J T; Chan, T L

    1989-01-01

    Carbon black aerosols were used as a probe of the pulmonary retention and clearance of submicron particles. Male Fischer rats (COBS CD) were exposed for 20 h/d, 7 d/wk for 1, 3, or 6 wk to either 7 +/- 2 mg/m3 carbon black or filtered air. The submicron aerosol (mass median aerodynamic diameter, MMAD, 0.24 microns) was generated with a Wright dust feed-cyclone system. Lung and hilar lymph node particle burdens were determined immediately following the exposure and at preselected intervals up to 1 yr postexposure. After 1-, 3-, and 6-wk exposures, the lung burdens were 1.1 +/- 0.1, 3.5 +/- 0.2, and 5.9 +/- 0.1 mg, respectively. One year after a 1-, 3-, or 6-wk exposure, 8%, 46%, and 61% of the initial lung burden remained in the lungs. Initially, the hilar lymph nodes contained 0.2%, 0.9%, and 2.0% of the lung burdens in the 3 exposure groups, respectively. At 1 yr postexposure, particle translocation from the lungs led to a rise in lymph node burdens to 1%, 21%, and 27% of the initial lung burden. The retention of carbon black in both the lungs and lymph nodes combined was 9%, 67%, and 89% for the 1-, 3-, and 6-wk exposed animals. Lung clearance was modeled as a compartmental system consisting of four lung compartments and a regional lymph node compartment. The results from the model are similar for carbon black and diesel engine exhaust particles. However, the compartmental kinetics of carbon black differed in two ways: the deposition efficiency in the alveolar region was lower than that for diesel exhaust particles, and there was earlier transport of particles to the regional lymph nodes. These results showed that when lung burdens reached 0.8 mg, lung clearance was decreased by 50% and lymphatic transport of insoluble particles was increased. PMID:2466129

  3. hZIP1 zinc uptake transporter down regulation and zinc depletion in prostate cancer

    Directory of Open Access Journals (Sweden)

    Kajdacsy-Balla André

    2005-09-01

    Full Text Available Abstract Background The genetic and molecular mechanisms responsible for and associated with the development and progression of prostate malignancy are largely unidentified. The peripheral zone is the major region of the human prostate gland where malignancy develops. The normal peripheral zone glandular epithelium has the unique function of accumulating high levels of zinc. In contrast, the ability to accumulate zinc is lost in the malignant cells. The lost ability of the neoplastic epithelial cells to accumulate zinc is a consistent factor in their development of malignancy. Recent studies identified ZIP1 (SLC39A1 as an important zinc transporter involved in zinc accumulation in prostate cells. Therefore, we investigated the possibility that down-regulation of hZIP1 gene expression might be involved in the inability of malignant prostate cells to accumulate zinc. To address this issue, the expression of hZIP1 and the depletion of zinc in malignant versus non-malignant prostate glands of prostate cancer tissue sections were analyzed. hZIP1 expression was also determined in malignant prostate cell lines. Results hZIP1 gene expression, ZIP1 transporter protein, and cellular zinc were prominent in normal peripheral zone glandular epithelium and in benign hyperplastic glands (also zinc accumulating glands. In contrast, hZIP1 gene expression and transporter protein were markedly down-regulated and zinc was depleted in adenocarcinomatous glands and in prostate intra-epithelial neoplastic foci (PIN. These changes occur early in malignancy and are sustained during its progression in the peripheral zone. hZIP1 is also expressed in the malignant cell lines LNCaP, PC-3, DU-145; and in the nonmalignant cell lines HPr-1 and BPH-1. Conclusion The studies clearly establish that hZIP1 gene expression is down regulated and zinc is depleted in adenocarcinomatous glands. The fact that all the malignant cell lines express hZIP1 indicates that the down-regulation

  4. Carbon particle induced foaming of molten sucrose for the preparation of carbon foams

    Energy Technology Data Exchange (ETDEWEB)

    Narasimman, R.; Vijayan, Sujith; Prabhakaran, K., E-mail: kp2952002@gmail.com

    2014-11-15

    Graphical abstract: - Highlights: • An easy method for the preparation of carbon foam from sucrose is presented. • Wood derived activated carbon particles are used to stabilize the molten sucrose foam. • The carbon foams show relatively good mechanical strength. • The carbon foams show excellent CO{sub 2} adsorption and oil absorption properties. • The process could be scaled up for the preparation of large foam bodies. - Abstract: Activated carbon powder was used as a foaming and foam setting agent for the preparation of carbon foams with a hierarchical pore structure from molten sucrose. The rheological measurements revealed the interruption of intermolecular hydrogen bonding in molten sucrose by the carbon particles. The carbon particles stabilized the bubbles in molten sucrose by adsorbing on the molten sucrose–gas interface. The carbon foams obtained at the activated carbon powder to sucrose weight ratios in the range of 0–0.25 had a compressive strength in the range of 1.35–0.31 MPa. The produced carbon foams adsorb 2.59–3.04 mmol/g of CO{sub 2} at 760 mmHg at 273 K and absorb oil from oil–water mixtures and surfactant stabilized oil-in-water emulsions with very good selectivity and recyclability.

  5. Method of producing carbon coated nano- and micron-scale particles

    Science.gov (United States)

    Perry, W. Lee; Weigle, John C; Phillips, Jonathan

    2013-12-17

    A method of making carbon-coated nano- or micron-scale particles comprising entraining particles in an aerosol gas, providing a carbon-containing gas, providing a plasma gas, mixing the aerosol gas, the carbon-containing gas, and the plasma gas proximate a torch, bombarding the mixed gases with microwaves, and collecting resulting carbon-coated nano- or micron-scale particles.

  6. Down regulation of Wnt signaling mitigates hypoxia-induced chemoresistance in human osteosarcoma cells.

    Directory of Open Access Journals (Sweden)

    Donald J Scholten

    Full Text Available Osteosarcoma (OS is the most common type of solid bone cancer and remains the second leading cause of cancer-related death for children and young adults. Hypoxia is an element intrinsic to most solid-tumor microenvironments, including that of OS, and is associated with resistance to therapy, poor survival, and a malignant phenotype. Cells respond to hypoxia through alterations in gene expression, mediated most notably through the hypoxia-inducible factor (HIF class of transcription factors. Here we investigate hypoxia-induced changes in the Wnt/β-catenin signaling pathway, a key signaling cascade involved in OS pathogenesis. We show that hypoxia results in increased expression and signaling activation of HIF proteins in human osteosarcoma cells. Wnt/β-catenin signaling is down-regulated by hypoxia in human OS cells, as demonstrated by decreased active β-catenin protein levels and axin2 mRNA expression (p<0.05. This down-regulation appears to rely on both HIF-independent and HIF-dependent mechanisms, with HIF-1α standing out as an important regulator. Finally, we show that hypoxia results in resistance of human OS cells to doxorubicin-mediated toxicity (6-13 fold increase, p<0.01. These hypoxic OS cells can be sensitized to doxorubicin treatment by further inhibition of the Wnt/β-catenin signaling pathway (p<0.05. These data support the conclusion that Wnt/β-catenin signaling is down-regulated in human OS cells under hypoxia and that this signaling alteration may represent a viable target to combat chemoresistant OS subpopulations in a hypoxic niche.

  7. 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

  8. 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.

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

    International Nuclear Information System (INIS)

    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.

  10. 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

  11. Cell surface modulation of gene expression in brain cells by down regulation of glucocorticoid receptors

    Energy Technology Data Exchange (ETDEWEB)

    McGinnis, J.F.; de Vellis, J.

    1981-02-01

    The concentration of glycerol-3-phosphate dehydrogenase (GPDH; sn-glycerol-3-phosphate:NAD/sup +/ 2-oxidoreductase, EC 1.1.1.8) had previously been determined to be regulated by glucocorticoids in rat brain cells in vivo and in cell culture. We now demonstrate that concanavalin A (Con A) can inhibit the induction of GPDH in a dose-dependent manner in C6 rat glioma cells and in primary cultures of rat brain oligodendrocytes. The inhibition specifically prevents the appearance of new molecules of GPDH, although Con A does not significantly inhibit protein synthesis in these cells, nor does it affect the activity of another solube enzyme, lactate dehydrogenase. The ability to block enzyme induction is not limited to Con A, because other lectins also inhibit induction. The molecular mechanism by which Con A inhibits GPDH induction appears to be by the down regulation of the cytoplasmic glucocorticoid receptors, because exposure to Con A results in the loss of more than 90% of the receptor activity. Con A does not inhibit the receptor assay and no direct interaction between the receptor and Con A could be demonstrated. This down regulation is not tumor cell specific and appears to be a general phenomenon, because it occurs in normal oligodendrocytes and even in normal astrocytes (a cell type in which the gene for GPDH is not expressed). The down regulation of glucocorticoid receptors in normal brain cells suggests two important corollaries. First, it demonstrates the existence of a rate-limiting step controlling the glucocorticoid-dependent gene expression in brain cells and possibly represents a regulatory site common to all glucocorticoid target cells. Second, it suggests that the response to glucocorticoids of oligodendrocytes and astrocytes can be regulated in vivo by cell surface contact with endogenous lectins, neighboring cells, or both.

  12. 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.

  13. 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.

  14. 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...

  15. RNAi-mediated down-regulation of SHATTERPROOF gene in transgenic oilseed rape

    OpenAIRE

    Kord, Hadis; Shakib, Ali Mohammad; Daneshvar, Mohammad Hossein; Azadi, Pejman; Bayat, Vahid; Mashayekhi, Mohsen; Zarea, Mahboobeh; Seifi, Alireza; Ahmad-Raji, Mana

    2014-01-01

    Oilseed rape is one of the important oil plants. Pod shattering is one of the problems in oilseed rape production especially in regions with dry conditions. One of the important genes in Brassica pod opening is SHATTERPROOF1 (SHP1). Down-regulation of BnSHP1 expression by RNAi can increase resistance to pod shattering. A 470 bp of the BnSHP1 cDNA sequence constructed in an RNAi-silencing vector was transferred to oilseed rape cv. SLM046. Molecular analysis of T2 transgenic plants by RT-PCR an...

  16. 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; Boding, Lasse; Larsen, Jeppe M; Leitges, Michael; Baier, Gottfried; Odum, Niels; Geisler, Carsten

    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...

  17. 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

  18. 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.

  19. Electron tomography of Pt nanocatalyst particles and their carbon support

    Energy Technology Data Exchange (ETDEWEB)

    Gontard, L Cervera [Department of Materials Science and Metallurgy, University of Cambridge, Pembroke Street, Cambridge CB2 3QZ (United Kingdom); Dunin-Borkowski, R E [Department of Materials Science and Metallurgy, University of Cambridge, Pembroke Street, Cambridge CB2 3QZ (United Kingdom); Chong, R K K [Department of Materials Science and Metallurgy, University of Cambridge, Pembroke Street, Cambridge CB2 3QZ (United Kingdom); Ozkaya, D [Johnson Matthey Technology Centre, Blount' s Court, Sonning Common, Reading RG4 9NH (United Kingdom); Midgley, P A [Department of Materials Science and Metallurgy, University of Cambridge, Pembroke Street, Cambridge CB2 3QZ (United Kingdom)

    2006-02-22

    Industrial nanocatalysts usually comprise crystalline particles of high atomic number that have sizes of between 1 and 20 nm and are supported or embedded in a lower atomic number matrix. The physical characterisation of the three-dimensional shapes and sizes of such particles can now be carried out using high-angle annular darkfield electron tomography. The spatial distribution of the particles with respect to their matrix is an issue of paramount importance for their performance as catalysts. Here, we show experimental electron tomography results from platinum particles dispersed in a carbon support. We show that both the high and the low atomic number regions of the same region of a sample can be characterised by using a combination of high and low angle annular dark field and bright field signals.

  20. Down-regulation of miR-192-5p protects from oxidative stress-induced acute liver injury.

    Science.gov (United States)

    Roy, Sanchari; Benz, Fabian; Alder, Jan; Bantel, Heike; Janssen, Joern; Vucur, Mihael; Gautheron, Jeremie; Schneider, Anne; Schüller, Florian; Loosen, Sven; Luedde, Mark; Koch, Alexander; Tacke, Frank; Luedde, Tom; Trautwein, Christian; Roderburg, Christoph

    2016-07-01

    miR-192-5p has gained increasing relevance in various diseases, however, its function in acute liver injury is currently unknown. We analysed miR-192-5p serum levels and hepatic miR-192-5p expression in mice after hepatic ischaemia and reperfusion (I/R) as well as in toxic liver injury. On a functional level, miRNA levels were analysed in the different hepatic cell-compartments and in the context of tumour necrosis factor (TNF)-dependent liver cell death. We detected increased serum levels of miR-192-5p after hepatic I/R- and carbon tetrachloride (CCl4)-induced liver injury. miR-192-5p levels correlated with the degree of liver damage and the presence of hepatic cell death detected by TUNEL stainings (terminal deoxynucleotidyltransferase-mediated dUTP biotin nick-end labelling stainings). Moreover, expression of miR-192-5p was increased in a hypoxia/reoxygenation (H/R) model of in vitro hepatocyte injury, supporting that the passive release of miR-192-5p represents a surrogate for hepatocyte death in liver injury. In critically ill patients, miR-192-5p levels were elevated selectively in patients with liver injury and closely correlated with the presence of hepatic injury. In contrast with up-regulated miR-192-5p in the serum, we detected a down-regulation of miR-192-5p in both injured mouse and human livers. Deregulation of miR-192-5p in livers was dependent on stimulation with TNF. Functional experiments confirmed a protective effect of down-regulation of miR-192-5p in hepatocytes, suggesting a role of miR-192-5p in limiting liver injury. Finally, we identified Zeb2, an important regulator of cell death, as a potential target gene mediating the function of miR-192-5p Our data suggest that miR-192-5p is involved in the regulation of liver cell death during acute liver injury and might represent a potent marker of hepatic injury. PMID:27129188

  1. 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

  2. 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.

  3. Potent anti-prostate cancer agents derived from a novel androgen receptor down-regulating agent.

    Science.gov (United States)

    Purushottamachar, Puranik; Khandelwal, Aakanksha; Vasaitis, Tadas S; Bruno, Robert D; Gediya, Lalji K; Njar, Vincent C O

    2008-04-01

    The search for novel androgen receptor (AR) down-regulating agents by catalyst HipHop pharmacophore modeling led to the discovery of some lead molecules. Unexpectedly, the effect of these leads on human prostate cancer LNCaP cell viability did not correlate with the ability of the compounds to cause down-regulation of AR protein expression. Through rational synthetic optimization of the lead compound (BTB01434), we have discovered a series of novel substituted diaryl molecules as potent anti-prostate cancer agents. Some compounds (1-6) were shown to be extremely potent inhibitors of LNCaP cell viability with GI(50) values in the nanomolar range (1.45-83 nM). The most potent compound (4-methylphenyl)[(4-methylphenyl)sulfonyl]amine (5) with a GI(50) value of 1.45 nM is 27,000 times more potent than our lead compound BTB01434 (GI(50)=39.8 microM). In addition, some of the compounds exhibited modest anti-androgenic activities and one was also a potent inhibitor (GI(50)=850 nM) of PC-3 (AR-null) cell growth. A clear structure-activity relationship (SAR) has been established for activity against LNCaP cells, where potent molecules possess two substituted/unsubstituted aromatic rings connected through a sulfonamide linker. These novel compounds are strong candidates for development for the treatment of hormone-sensitive and importantly hormone-refractory prostate cancers in humans. PMID:18316193

  4. 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

  5. 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.

  6. 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.

  7. 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.

  8. Amino acid limitation induces down-regulation of WNT5a at transcriptional level

    International Nuclear Information System (INIS)

    An aberrant WNT signaling contributes to the development and progression of multiple cancers. WNT5a is one of the WNT signaling molecules. This study was designed to test the hypothesis that amino acid deprivation induces changes in the WNT signaling pathway in colon cancer cells. Results showed that targets of the amino acid response pathway, ATF3 and p21, were induced in the human colon cancer cell line SW480 during amino acid limitation. There was a significant decrease in the WNT5a mRNA level following amino acid deprivation. The down-regulation of WNT5a mRNA by amino acid deprivation is not due to mRNA destabilization. There is a reduction of nuclear β-catenin protein level by amino acid limitation. Under amino acid limitation, phosphorylation of ERK1/2 was increased and the blockage of ERK1/2 by the inhibitor U0126 partially restored WNT5a mRNA level. In conclusion, amino acid limitation in colon cancer cells induces phosphorylation of ERK1/2, which then down-regulates WNT5a expression.

  9. 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.

  10. 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.

  11. 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...

  12. 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...

  13. 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...

  14. Down-regulation of SOSTDC1 promotes thyroid cancer cell proliferation via regulating cyclin A2 and cyclin E2

    OpenAIRE

    Liang, Weiwei; Guan, Hongyu; He, Xiaoying; KE, WEIJIAN; Xu, Lijuan; Liu, Liehua; Xiao, Haipeng; Li, Yanbing

    2015-01-01

    Sclerostin domain containing protein 1 (SOSTDC1) is down-regulated and acts as a tumor suppressor in some kinds of cancers. However, the expression pattern and biological significance of SOSTDC1 in thyroid cancer are largely unknown. We demonstrated that SOSTDC1 was significantly down-regulated in thyroid cancer. Ectopic over-expression of SOSTDC1 inhibited proliferation and induced G1/S arrest in thyroid cancer cells. Moreover, SOSTDC1 over-expression suppressed the growth of tumor xenograft...

  15. Characterization of calcium carbonate sorbent particle in furnace environment

    International Nuclear Information System (INIS)

    The oxy-fuel combustion system is a promising technology to control CO2 and NOX emissions. Furthermore, sulfation reaction mechanism under CO2-rich atmospheric condition in a furnace may lead to in-furnace desulfurization. In the present study, we evaluated characteristics of calcium carbonate (CaCO3) sorbent particles under different atmospheric conditions. To examine the physical/chemical characteristics of CaCO3, 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 CaCO3 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 CO2 atmosphere due to the higher CO2 partial pressure. Instead, the sintering effect was dominant in the CO2 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 CO2 atmospheres.

  16. Characterization of calcium carbonate sorbent particle in furnace environment.

    Science.gov (United States)

    Lee, Kang Soo; Jung, Jae Hee; Keel, Sang In; Yun, Jin Han; Min, Tai Jin; Kim, Sang Soo

    2012-07-01

    The oxy-fuel combustion system is a promising technology to control CO₂ and NO(x) emissions. Furthermore, sulfation reaction mechanism under CO₂-rich atmospheric condition in a furnace may lead to in-furnace desulfurization. In the present study, we evaluated characteristics of calcium carbonate (CaCO₃) sorbent particles under different atmospheric conditions. To examine the physical/chemical characteristics of CaCO₃, 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 CaCO₃ 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 CO₂ atmosphere due to the higher CO₂ partial pressure. Instead, the sintering effect was dominant in the CO₂ 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 CO₂ atmospheres. PMID:22578525

  17. Evidence of old soil carbon in grass biosilica particles

    Science.gov (United States)

    Reyerson, P. E.; Alexandre, A.; Harutyunyan, A.; Corbineau, R.; Martinez De La Torre, H. A.; Badeck, F.; Cattivelli, L.; Santos, G. M.

    2015-09-01

    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 grasslands 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 is found that phytC is partially derived from soil carbon that can be several thousand years old. The accumulation of old soil organic matter derived carbon in plant biosilica suggests that Si absorption and phytolith production promote old soil organic carbon mobilization. Although the magnitude of this mechanism still needs to be properly assessed at plant and ecosystem scales, its confirmation alone argues against attempts to use phytC as a proxy of plant carbon and call for the reexamination of phytolith atmospheric CO2 biosequestration estimates.

  18. Evidence of old soil carbon in grass biosilica particles

    Directory of Open Access Journals (Sweden)

    P. E. Reyerson

    2015-09-01

    Full Text Available 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 grasslands 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 is found that phytC is partially derived from soil carbon that can be several thousand years old. The accumulation of old soil organic matter derived carbon in plant biosilica suggests that Si absorption and phytolith production promote old soil organic carbon mobilization. Although the magnitude of this mechanism still needs to be properly assessed at plant and ecosystem scales, its confirmation alone argues against attempts to use phytC as a proxy of plant carbon and call for the reexamination of phytolith atmospheric CO2 biosequestration estimates.

  19. Vitamin A induces inhibitory histone methylation modifications and down-regulates trained immunity in human monocytes

    DEFF Research Database (Denmark)

    Arts, Rob J W; Blok, Bastiaan A; van Crevel, Reinout;

    2015-01-01

    assessed. ATRA inhibited cytokine responses upon restimulation of monocytes, and this effect was exerted through increased expression of SUV39H2, a histone methyltransferase that induces the inhibitory mark H3K9me3. H3K9me3 at promoter sites of several cytokines was up-regulated by ATRA, and inhibition of...... SUV39H2 restored cytokine production. In addition to H3K9me3, the stimulatory histone mark H3K4me3 was down-regulated by ATRA at several promoter locations of cytokine genes. Therefore, we can conclude that ATRA inhibits cytokine production in models of direct stimulation or BCG-induced trained...

  20. Impaired down-regulation of negative emotion in self-referent social situations in bipolar disorder

    DEFF Research Database (Denmark)

    Kjærstad, Hanne L; Vinberg, Maj; Goldin, Philippe R;

    2016-01-01

    naturally or dampen their emotional response to positive and negative social scenarios and associated self-beliefs. They were also given an established experimental task for comparison, involving reappraisal of negative affective picture stimuli, as well as a questionnaire of habitual ER strategies. BD...... patients showed reduced ability to down-regulate emotional responses in negative, but not positive, social scenarios relative to healthy controls and UD patients. In contrast, there were no between-group differences in the established ER task or in self-reported habitual reappraisal strategies. Findings......Emotion dysregulation is a core feature of bipolar disorder (BD) that persists into periods of remission. Neuroimaging studies show aberrant neural responses during emotion regulation (ER) in patients with BD relative to healthy controls, but behavioural evidence for ER deficits is sparse...

  1. 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.

  2. 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...

  3. Design and Optimisation of Bioactive Cyclic Peptides: Generation of a Down-Regulator of TNF Secretion

    Directory of Open Access Journals (Sweden)

    Roger New

    2014-12-01

    Full Text Available Although strong binding interactions between protein receptor and ligand do not require the participation of a large number of amino acids in either site, short peptide chains are generally poor at recreating the types of protein-protein interactions which take place during cell recognition and signalling process, probably because their flexible backbones prevent the side chains from forming sufficiently rigid and stable epitopes, which can take part in binding with the desired strength and specificity. In a recently-reported study, it was shown that a proto-epitope containing F, R and S amino acids has the ability to down-regulate TNF secretion by macrophages. This paper extends these findings, putting those amino acids into a short cyclic peptide scaffold, and determining the optimal configuration required to overcome the problems of conformational instability, and give rise to molecules which have potential as therapeutic agents in human disease, such as rheumatoid arthritis.

  4. RNF4 negatively regulates NF-κB signaling by down-regulating TAB2.

    Science.gov (United States)

    Tan, Bo; Mu, Rui; Chang, Yan; Wang, Yu-Bo; Wu, Min; Tu, Hai-Qing; Zhang, Yu-Cheng; Guo, Sai-Sai; Qin, Xuan-He; Li, Tao; Li, Wei-Hua; Zhang, Xue-Min; Li, Ai-Ling; Li, Hui-Yan

    2015-09-14

    Most of NF-κB (nuclear factor kappa B) signaling molecules have various types of post-translational modifications. In this study, we focused on ubiquitination and designed a siRNA library including most ubiquitin-binding domains. With this library, we identified several candidate regulators of canonical NF-κB pathway, including RNF4. Overexpression of RNF4 impaired NF-κB activation in a dose-dependent manner, whereas RNF4 knockdown potentiated NF-κB activation. We showed that RNF4 interacts with the TAK1-TAB2-TAB3 complex, but not TAB1. Further, we found that RNF4 specifically down-regulated TAB2 through a lysosomal pathway, and knockdown of RNF4 impaired endogenous TAB2 degradation. Therefore, our findings will provide new insights into the negative regulation of NF-κB signaling. PMID:26299341

  5. 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

  6. Down-Regulation of Nogo-B Expression as a Newly Identified Feature of Intrahepatic Cholangiocarcinoma.

    Science.gov (United States)

    Nanashima, Atsushi; Hatachi, Go; Tominaga, Tetsurou; Murakami, Goushi; Takagi, Katsunori; Arai, Junichi; Wada, Hideo; Nagayasu, Takeshi; Sumida, Yorihisa

    2016-01-01

    Nogo-B, located in the endoplasmic reticulum, is an isoform belonging to the reticulon protein family, which is expressed specifically in cholangiocytes and non-parenchymal cells in the liver. Nogo-B expression is down-regulated with the progression of liver fibrosis, but its distinct function in liver malignancies has not been fully clarified. We have hypothesized that Nogo-B expression may be altered in intrahepatic cholangiocarcinoma (ICC), a relatively rare type of primary liver cancer with highly malignant behavior. The present study aimed to investigate the relationship between Nogo-B expression, assessed by immunohistochemical staining, and clinicopathological factors and prognosis in 34 ICC patients. Positive expression was observed in 19 (56%) of 34 ICC specimens: 6 patients (18%) with positivity levels of 1+ (positive cells in 10-50% of cancer cells) and 13 patients (38%) with 2+ (positive cells over 50%). Importantly, the remaining 15 patients (44%) were categorized as negative expression (Nogo-B-positive cells, less than 10%). Conversely, the mass-forming type of ICC tended to express Nogo-B with the degree of 2+ positivity, compared to the periductal infiltration type (p = 0.064), and the mass-forming type showed a better 5-year survival rate (66% vs. 5%) after hepatectomy (p < 0.05). However, the degree of positivity was not associated with tumor relapse rate, disease-free and overall survival, although each of the periductal infiltration type, intrahepatic metastasis, larger tumor size, and lower microvessel counts was associated with lower survival rates. We propose that Nogo-B expression is down-regulated in ICC, the implication of which, however, remains to be investigated. PMID:26656426

  7. 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

  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. 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

  10. 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

  11. 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.

  12. Antibacterial activity of carbon-coated zinc oxide particles.

    Science.gov (United States)

    Sawai, Jun; Yamamoto, Osamu; Ozkal, Burak; Nakagawa, Zenbe-E

    2007-03-01

    Particles of ZnO coated with carbon (ZnOCC) were prepared and evaluated for their antibacterial activity. ZnO powder and poly(vinyl alcohol) (PVA) (polymerization degree: 2,000-95,000) were mixed at a mass ratio (ZnO/PVA) of 1, and then heated at 500-650 degree C for 3 h under argon gas with a flow rate of 50ml/min. Carbon deposited on the ZnOCC surface was amorphous as revealed by X-ray diffraction studies. The ZnOCC particles maintained their shape in water, even under agitation. The antibacterial activity of ZnOCC powder against Staphylococcus aureus was evaluated quantitatively by measuring the change in the electrical conductivity of the growth medium caused by bacterial metabolism (conductimetric assay). The conductivity curves obtained were analyzed using the growth inhibition kinetic model proposed by Takahashi for calorimetric evaluation, allowing the estimation of the antibacterial efficacy and kinetic parameters of ZnOCC. In a previous study, when ZnO was immobilized on materials, such as activated carbon, the amount of ZnO immobilized was approximately 10-50%, and the antibacterial activity markedly decreased compared to that of the original ZnO. On the other hand, the ZnOCC particles prepared in this study contained approximately 95% ZnO and possessed antibacterial activity similar to that of pure ZnO. The carbon-coating treatment could maintain the antibacterial efficacy of the ZnO and may be useful in the develop-ment of multifunctional antimicrobial materials. PMID:17408004

  13. 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...

  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. Mass spectrometry of refractory black carbon particles from six sources: carbon-cluster and oxygenated ions

    Directory of Open Access Journals (Sweden)

    J. C. Corbin

    2013-10-01

    Full Text Available We discuss the major mass spectral features of different types of refractory carbonaceous particles, ionized after laser vapourization with an Aerodyne High-Resolution Soot-Particle Aerosol Mass Spectrometer (SP-AMS. The SP-AMS was operated with a switchable 1064 nm laser and a 600 °C thermal vapourizer, yielding respective measurements of the refractory and non-refractory particle components. Six samples were investigated, all of which were composed primarily of refractory material: fuel-rich and fuel-lean propane/air diffusion-flame combustion particles; graphite-spark-generated particles; a commercial Fullerene-enriched Soot; Regal Black, a commercial carbon black; and nascent aircraft-turbine combustion particles. All samples exhibited a spectrum of carbon-cluster ions Cxn+ in their refractory mass spectrum. Smaller clusters (xxn+ distribution. For Fullerene Soot, fuel-rich-flame particles and spark-generated particles, significant Cxn+ clusters at x≫6 were present, with significant contributions from multiply-charged ions (n>1. In all six cases, the ions C1+ and C3+ contributed over 60% to the total C1x+ intensity. Furthermore, the ratio of these major ions C1+/C3+ could be used to predict whether significant Cxn+ signals with x>5 were present. When such signals were present, C1+/C3+ was close to 1. When absent, C1+/C3+ was Significant refractory oxygenated ions such as CO+ and CO2+ were also observed for all samples. We discuss these signals in detail for Regal Black, and describe their formation via decomposition of oxygenated moieties incorporated into the refractory carbon structure. These species may be of importance in atmospheric processes such as water uptake, aging and heterogeneous chemistry.

  17. Down-Regulation of Small Rubber Particle Protein Expression Affects Integrity of Rubber Particles and Rubber Content in Taraxacum brevicorniculatum

    Czech Academy of Sciences Publication Activity Database

    Hillebrand, A.; Post, J. J.; Wurbs, D.; Wahler, D.; Lenders, D.; Krzyžánek, Vladislav; Pruefer, D.; Gronover, CH. S.

    2012-01-01

    Roč. 7, č. 7 (2012), e41874:1-9. E-ISSN 1932-6203 Institutional support: RVO:68081731 Keywords : Hevea-Brasiliensis * Parthenium-Argentatum * Elongation-Factor * Silencing Affects * Surface-Structure * Oil Bodies * Latex * Prenyltransferase * Biosynthesis * Stability Subject RIV: CE - Biochemistry Impact factor: 3.730, year: 2012

  18. 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

    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...... 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.......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...

  19. Down-regulation of SOSTDC1 promotes thyroid cancer cell proliferation via regulating cyclin A2 and cyclin E2

    Science.gov (United States)

    He, Xiaoying; Ke, Weijian; Xu, Lijuan; Liu, Liehua; Xiao, Haipeng; Li, Yanbing

    2015-01-01

    Sclerostin domain containing protein 1 (SOSTDC1) is down-regulated and acts as a tumor suppressor in some kinds of cancers. However, the expression pattern and biological significance of SOSTDC1 in thyroid cancer are largely unknown. We demonstrated that SOSTDC1 was significantly down-regulated in thyroid cancer. Ectopic over-expression of SOSTDC1 inhibited proliferation and induced G1/S arrest in thyroid cancer cells. Moreover, SOSTDC1 over-expression suppressed the growth of tumor xenografts in nude mice. We also found that elevated SOSTDC1 led to inhibition of cyclin A2 and cyclin E2. Together, our results demonstrate that SOSTDC1 is down-regulated in thyroid cancer and might be a potential therapeutic target in the treatment of thyroid cancer. PMID:26378658

  20. Down-regulation of the cyprinid herpesvirus-3 annotated genes in cultured cells maintained at restrictive high temperature.

    Science.gov (United States)

    Ilouze, Maya; Dishon, Arnon; Kotler, Moshe

    2012-10-01

    Cyprinid herpesvirus-3 (CyHV-3) is a member of the Alloherpesviridae, in the order Herpesvirales. It causes a fatal disease in carp and koi fish. The disease is seasonal and is active when water temperatures ranges from 18 to 28 °C. Little is known about how and where the virus is preserved between the permissive seasons. The hallmark of the herpesviruses is their ability to become latent, persisting in the host in an apparently inactive state for varying periods of time. Hence, it could be expected that CyHV-3 enter a latent period. CyHV-3 has so far been shown to persist in fish maintained under restrictive temperatures, while shifting the fish to permissive conditions reactivates the virus. Previously, we demonstrated that cultured cells infected with CyHV-3 at 22 °C and subsequently transferred to a restrictive temperature of 30 °C preserve the virus for 30 days. The present report shows that cultured carp cells maintained and exposed to CyHV-3 at 30 °C are abortively infected; that is, autonomous viral DNA synthesis is hampered and the viral genome is not multiplied. Under these conditions, 91 of the 156 viral annotated ORFs were initially transcribed. These transcripts were down-regulated and gradually shut off over 18 days post-infection, while two viral transcripts encoded by ORFs 114 and 115 were preserved in the infected cells for 18 days p.i. These experiments, carried out in cultured cells, suggest that fish could be infected at a high non-permissive temperature and harbor the viral genome without producing viral particles. PMID:22841492

  1. 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.)

  2. 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.

  3. 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...

  4. 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.

  5. 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.

  6. In socially isolated mice, the reversal of brain allopregnanolone down-regulation mediates the anti-aggressive action of fluoxetine

    OpenAIRE

    Pinna, Graziano; Dong, Erbo; Matsumoto, Kinzo; Costa, Erminio; Guidotti, Alessandro

    2003-01-01

    Social isolation (SI) of male mice lasting >4 weeks is associated with aggression toward intruders and a down-regulation of brain allopregnanolone (Allo) content. SI of female mice fails to down-regulate brain Allo content or to induce aggressiveness. Fluoxetine (Prozac in clinical use) is an S- and R-fluoxetine (FLX) mixture, which in mammals is metabolized into S- and R-norfluoxetine (NFLX). The S isomers of FLX and NFLX are more active than their respective R isomers in normalizing brain A...

  7. 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.

  8. 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

  9. 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.

  10. Endometrial response to IVF hormonal manipulation: Comparative analysis of menopausal, down regulated and natural cycles

    Directory of Open Access Journals (Sweden)

    Gayer Nalini

    2004-04-01

    Full Text Available Abstract Background Uterine luminal epithelial cell response to different hormonal strategies was examined to determine commonality when an endometrium attains a receptive, stimulated, morphological profile that may lead to successful implantation. Methods Endometrial biopsies from 3 cohorts of patients were compared. The tissue samples taken from these patients were categorized into 8 different groups according to their baseline and the hormone regime used. Results Pre-treatment natural cycle tissue was variable in appearance. Downregulation with a GnRH analogue tissue appeared menopausal in character. HRT after downregulation resulted in tissue uniformity. HRT in menopause resulted in a 'lush' epithelial surface. HST in the natural cycle improved the morphology with significant difference in secretion between the two regimes examined. Conclusions Down regulation plus HRT standardized surface appearance but tissue response is significantly different from the natural cycle, natural cycle plus HRT or menopause plus HRT. HRT in menopause reinstates tissue to a state similar to a natural cycle but significantly different from a natural cycle plus HST. HST with a natural cycle is similar to tissue from the natural cycle but significant differences reflect the influence of the particular hormones present (at any point within the cycle.

  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. 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.

  14. 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

  15. Znhit1 causes cell cycle arrest and down-regulates CDK6 expression

    International Nuclear Information System (INIS)

    Cyclin-dependent kinase 6 (CDK6) is the key element of the D-type cyclin holoenzymes which has been found to function in the regulation of G1-phase of the cell cycle and is presumed to play important roles in T cell function. In this study, Znhit1, a member of a new zinc finger protein family defined by a conserved Zf-HIT domain, induced arrest in the G1-phase of the cell cycle in NIH/3T3 cells. Of the G1 cell cycle factors examined, the expression of CDK6 was found to be strongly down-regulated by Znhit1 via transcriptional repression. This effect may have correlations with the decreased acetylation level of histone H4 in the CDK6 promoter region. In addition, considering that CDK6 expression predominates in T cells, the negative regulatory role of Znhit1 in TCR-induced T cell proliferation was validated using transgenic mice. These findings identified Znhit1 as a CDK6 regulator that plays an important role in cell proliferation.

  16. 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.

  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 osteopontin attenuates breast tumour progression in vivo.

    Science.gov (United States)

    Chakraborty, Goutam; Jain, Shalini; Patil, Tushar V; Kundu, Gopal C

    2008-12-01

    Development of breast tumour malignancies results in enhanced expression of various oncogenic molecules. Elevated expression of osteopontin (OPN) in higher grades of breast carcinoma correlates with enhanced expressions of several oncogenic molecules (urokinase-type plasminogen activator [uPA], matrix metalloproteinase-2/-9 [MMP-2 and -9]) and increased angiogenic potential of breast carcinoma. In this study, using in vitro and multiple in vivo models, we have demonstrated that silencing of OPN by its specific small interfering RNA (siRNA) down-regulates the expressions of oncogenic molecules such as uPA, MMP-2 and -9 resulting in inhibition of in vitro cell motility and in vivo tumourigenicity in mice. Moreover our results demonstrated that OPN-/- mice showed slower progression of tumour growth in breast cancer model as compared to wild-type mice. Furthermore, the data showed that injection of carcinogenic compound, pristane (2, 6,10,14-tetramethylpen-tadecane) induces breast tumour progression leading to enhanced expression of OPN and other oncogenic molecules in mammary fat pad of nude- and wild-type mice but not in OPN-/- mice. However, intratumoural injection of OPN siRNA to pristane-induced tumour significantly suppressed these effects. Our data revealed that knocking down of OPN effectively curb breast cancer progression and further suggested that developing of OPN-based therapeutics might be an emerging approach for the next generation of breast cancer management. PMID:18266970

  19. Bax Inhibitor-1 down-regulation in the progression of chronic liver diseases

    Directory of Open Access Journals (Sweden)

    Burra Patrizia

    2010-04-01

    Full Text Available Abstract Background Bax inhibitor-1 (BI-1 is an evolutionary conserved endoplasmic reticulum protein that, when overexpressed in mammalian cells, suppresses the apoptosis induced by Bax, a pro-apoptotic member of the Bcl-2 family. The aims of this study were: (1 to clarify the role of intrinsic anti- and pro-apoptotic mediators, evaluating Bax and BI-1 mRNA and protein expressions in liver tissues from patients with different degrees of liver damage; (2 to determine whether HCV and HBV infections modulate said expression. Methods We examined 62 patients: 39 with chronic hepatitis (CH (31 HCV-related and 8 HBV-related; 7 with cirrhosis (6 HCV-related and 1 HBV-related; 13 with hepatocellular carcinoma (HCC [7 in viral cirrhosis (6 HCV- and 1 HBV-related, 6 in non-viral cirrhosis]; and 3 controls. Bax and BI-1 mRNAs were quantified by real-time PCR, and BI-1 protein expression by Western blot. Results CH tissues expressed significantly higher BI-1 mRNA levels than cirrhotic tissues surrounding HCC (P Conclusions BI-1 expression is down-regulated as liver damage progresses. The high BI-1 mRNAs levels observed in early liver disease may protect virus-infected cells against apoptosis, while their progressive downregulation may facilitate hepatocellular carcinogenesis. HCV genotype seems to have a relevant role in Bax transcript expression.

  20. Down-Regulation of Gene Expression by RNA-Induced Gene Silencing

    Science.gov (United States)

    Travella, Silvia; Keller, Beat

    Down-regulation of endogenous genes via post-transcriptional gene silencing (PTGS) is a key to the characterization of gene function in plants. Many RNA-based silencing mechanisms such as post-transcriptional gene silencing, co-suppression, quelling, and RNA interference (RNAi) have been discovered among species of different kingdoms (plants, fungi, and animals). One of the most interesting discoveries was RNAi, a sequence-specific gene-silencing mechanism initiated by the introduction of double-stranded RNA (dsRNA), homologous in sequence to the silenced gene, which triggers degradation of mRNA. Infection of plants with modified viruses can also induce RNA silencing and is referred to as virus-induced gene silencing (VIGS). In contrast to insertional mutagenesis, these emerging new reverse genetic approaches represent a powerful tool for exploring gene function and for manipulating gene expression experimentally in cereal species such as barley and wheat. We examined how RNAi and VIGS have been used to assess gene function in barley and wheat, including molecular mechanisms involved in the process and available methodological elements, such as vectors, inoculation procedures, and analysis of silenced phenotypes.

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

    Science.gov (United States)

    Li, Liang-Dong; Sun, He-Fen; Liu, Xue-Xiao; Gao, Shui-Ping; Jiang, Hong-Lin; Hu, Xin; Jin, Wei

    2015-01-01

    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. PMID:26641458

  2. 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.

  3. Autophagic down-regulation in motor neurons remarkably prolongs the survival of ALS mice.

    Science.gov (United States)

    Hsueh, Kuo-Wei; Chiou, Tzyy-Wen; Chiang, Shu-Fen; Yamashita, Toru; Abe, Koji; Borlongan, Cesar V; Sanberg, Paul R; Huang, Angela Yu Hsuan; Lin, Shinn-Zong; Harn, Horng-Jyh

    2016-09-01

    Amyotrophic lateral sclerosis (ALS) is a lethal degenerating disease, characterized by progressive muscular atrophy without any effective treatment. Here, we demonstrated the efficacy of abrograting autophagy in motor neurons (MN) by treatment with n-butylidenephthalide (n-BP) in ALS transgenic mice (SOD1(G93A)). Pre-symptomatic oral administration of 250 mg/kg/bid n-BP significantly prolonged the survival period (203.9 ± 18.3 days), improved motor function, and attenuated MN loss compared to vehicle control (126.4 ± 7.2 days). This prolonged survival of ALS mice is much more robust than that reported with riluzole (140 days), which is an approved clinical therapy for ALS. The therapeutic mechanism targeted by n-BP involved the autophagic pathway as evidenced by decreased LC3-II expression (a biomarker of autophagy), enhanced mTOR levels, and attenuated autophagic activity, altogether increasing MN survival in a dose-dependent manner. This result was also confirmed by double transgenic mice (SOD1(G93A):LC3-GFP) which showed that oral administration of n-BP reduced GFP density and decreased caspase-3 expression. In addition, electron microscopy revealed that n-BP administration not only decreased autophagosome number but also reduced morphological dysfunction of mitochondria. In summary, these results indicate that down-regulation of autophagy activation via n-BP may pose as a therapeutic regimen for ALS and relevant neurodegenerative diseases. PMID:27059126

  4. TGFβ-pathway is down-regulated in a uterine carcinosarcoma: a case study.

    Science.gov (United States)

    Semczuk, Andrzej; Zakrzewski, Piotr K; Forma, Ewa; Cygankiewicz, Adam I; Semczuk-Sikora, Anna; Bryś, Magdalena; Rechberger, Tomasz; Krajewska, Wanda M

    2013-11-01

    Data assessing the role of various genetic alterations in uterine carcinosarcoma (CS), particularly the transforming growth factors-β (TGFβ) that play a crucial role in many cellular processes, including proliferation, differentiation, adhesion and migration, are scarce. TGFβ exert their effects through specific receptors and associated auxiliary receptors. In the current study, we investigated the expression of TGFβ isoforms and their receptors, as well as selected genes in a case of CS. We applied the real-time fluorescence detection PCR method with FAM dye-labeled TaqMan specific probes. In a comparison to the normal counterpart, TGFB1, TGFB2, TGFBRII, TGFBR3, ENG and CD109 were all down-regulated in uterine CS samples at different extents. BIRC5 and hTERT, markers of tumor survival, were up-regulated in CS as compared with normal counterparts. A concomitant increase of the hypoxia marker HIF1A expression pattern was noted, whereas the expression of GPR120, responsible for free fatty acids sensing, was not different in both counterparts evaluated. In conclusion, deregulation of various cellular mechanisms in uterine CS is associated with alterations at many levels - cell growth and proliferation, apoptosis, and impaired response to stimuli from extracellular environment. PMID:23932095

  5. Down regulated lncRNA MEG3 eliminates mycobacteria in macrophages via autophagy

    Science.gov (United States)

    Pawar, Kamlesh; Hanisch, Carlos; Palma Vera, Sergio Eliseo; Einspanier, Ralf; Sharbati, Soroush

    2016-01-01

    Small non-coding RNA play a major part in host response to bacterial agents. However, the role of long non-coding RNA (lncRNA) in this context remains unknown. LncRNA regulate gene expression by acting e.g. as transcriptional coactivators, RNA decoys or microRNA sponges. They control development, differentiation and cellular processes such as autophagy in disease conditions. Here, we provide an insight into the role of lncRNA in mycobacterial infections. Human macrophages were infected with Mycobacterium bovis BCG and lncRNA expression was studied early post infection. For this purpose, lncRNA with known immune related functions were preselected and a lncRNA specific RT-qPCR protocol was established. In addition to expression-based prediction of lncRNA function, we assessed strategies for thorough normalisation of lncRNA. Arrayed quantification showed infection-dependent repression of several lncRNA including MEG3. Pathway analysis linked MEG3 to mTOR and PI3K-AKT signalling pointing to regulation of autophagy. Accordingly, IFN-γ induced autophagy in infected macrophages resulted in sustained MEG3 down regulation and lack of IFN-γ allowed for counter regulation of MEG3 by viable M. bovis BCG. Knockdown of MEG3 in macrophages resulted in induction of autophagy and enhanced eradication of intracellular M. bovis BCG. PMID:26757825

  6. 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

  7. Differential gene expression induced by high LET charged particles in normal human fibroblasts

    International Nuclear Information System (INIS)

    We investigated differential gene expression of normal human skin HSF42 fibroblasts induced by heavy ions using cDNA microarray technology. Irradiation with 3 types of heavy ions was performed at Heavy Ion Medical Accelerator in Chiba (HIMAC) facility. Out of 7458 genes, we found 61 significant genes (40 up-regulated and 21 down-regulated) that distinguished between human skin fibroblast HSF42 cells non-irradiated and irradiated with 1 Gy of neon particles and 62 significant genes (48 up-regulated and 14 down-regulated) that distinguished between HSF42 cells non-irradiated and irradiated with 1 Gy of silicon particles. Furthermore, we are going to analyze profiles of HSF42 cells exposed to carbon particles and compare those profiles between different types of beams. (author)

  8. 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.

  9. Herbivory of wild Manduca sexta causes fast down-regulation of photosynthetic efficiency in Datura wrightii: an early signaling cascade visualized by chlorophyll fluorescence.

    Science.gov (United States)

    Barron-Gafford, Greg A; Rascher, Uwe; Bronstein, Judith L; Davidowitz, Goggy; Chaszar, Brian; Huxman, Travis E

    2012-09-01

    Plants experiencing herbivory suffer indirect costs beyond direct loss of leaf area, but differentially so based on the herbivore involved. We used a combination of chlorophyll fluorescence imaging and gas exchange techniques to quantify photosynthetic performance, the efficiency of photochemistry, and heat dissipation to examine immediate and longer-term physiological responses in the desert perennial Datura wrightii to herbivory by tobacco hornworm, Manduca sexta. Herbivory by colony-reared larvae yielded no significant reduction in carbon assimilation, whereas herbivory by wild larvae induced a fast and spreading down-regulation of photosynthetic efficiency, resulting in significant losses in carbon assimilation in eaten and uneaten leaves. We found both an 89 % reduction in net photosynthetic rates in herbivore-damaged leaves and a whole-plant response (79 % decrease in undamaged leaves from adjacent branches). Consequently, herbivory costs are higher than previously estimated in this well-studied plant-insect interaction. We used chlorophyll fluorescence imaging to elucidate the mechanisms of this down-regulation. Quantum yield decreased up to 70 % in a small concentric band surrounding the feeding area within minutes of the onset of herbivory. Non-photochemical energy dissipation by the plant to avoid permanent damage was elevated near the wound, and increased systematically in distant areas of the leaf away from the wound over subsequent hours. Together, the results underscore not only potential differences between colony-reared and wild-caught herbivores in experimental studies of herbivory but also the benefits of quantifying physiological responses of plants in unattacked leaves. PMID:22576017

  10. Determination of Effective Particle Density for Sterically Stabilized Carbon Black Particles: Effect of Diblock Copolymer Stabilizer Composition.

    Science.gov (United States)

    Growney, David J; Fowler, Patrick W; Mykhaylyk, Oleksandr O; Fielding, Lee A; Derry, Matthew J; Aragrag, Najib; Lamb, Gordon D; Armes, Steven P

    2015-08-18

    Two poly(styrene-b-hydrogenated isoprene) (PS-PEP) copolymers and a poly(styrene-b-hydrogenated butadiene) (PS-PB) diblock copolymer of differing polystyrene content (20, 28 or 35 mol %) and molecular weight (117-183 kg mol(-1)) are examined. These copolymers form star-like micelles in n-dodecane, as judged by TEM, DLS, and SAXS studies. At ambient temperature, such micelles are known to adsorb intact onto a model colloidal substrate such as carbon black, conferring a high degree of dispersion (Growney, D. J.; Mykhaylyk, O. O.; Armes, S. P. Langmuir 2014, 30, 6047). Isotherms for micellar adsorption on carbon black at 20 °C are constructed using a supernatant depletion assay based on UV spectroscopy by utilizing the aromatic chromophore in the polystyrene block. Perhaps surprisingly, the diblock copolymer with the lowest polystyrene content has the strongest affinity for the carbon black particles. Assuming that the star-like diblock copolymer micelles adsorb onto carbon black to form hemi-micelles with a stabilizer layer thickness equal to the mean micelle radius, the effective particle density of the resulting sterically stabilized carbon black particles in n-dodecane can be estimated from the SAXS micelle dimensions based on geometric considerations. As an approximation, a spherical core-shell morphology was assumed, and the primary grain size of the carbon black particles was determined to be 74 nm diameter as judged by BET surface area analysis. Using this approach, effective particle densities of 0.90, 0.91, and 0.92 g cm(-3) were calculated for sterically stabilized carbon black particles prepared using the PS-PB20, PS-PEP28, and PS-PEP35 diblock copolymers, respectively. These densities are significantly lower than that of carbon black (1.89 g cm(-3)), which indicates that the sterically stabilized carbon black particles are substantially solvated. Since the rate of sedimentation of the sterically stabilized carbon black particles depends on the density

  11. 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...

  12. Dissociation of carbon dioxide and creation of carbon particles and films at room temperature

    International Nuclear Information System (INIS)

    As fluids approach their gas-liquid critical points, the physical properties such as the specific heat and compressibility diverge due to the formation of large molecular clusters. Incident light cannot penetrate near-critical fluids because of the large clusters, a phenomenon known as critical opalescence. In this paper, we irradiate near-critical carbon dioxide (ncCO2), the critical temperature and pressure of which are 31.00C and 7.38 MPa, with a laser beam of 213, 266, 355 and 532 nm wavelength and show that CO2 is dissociated and particles are produced when the system is set so close to the critical point that critical opalescence occurs in the case of 213 and 266 nm wavelength, whereas no particles are produced when the temperature is made to deviate from the critical value. We also apply a dc electric field to ncCO2 during irradiation with a laser beam of 213 and 266 nm wavelength and find that particles are formed on both anode and cathode. As the intensity of the electric field increases, films are formed on the electrodes. Electron diffraction patterns and energy-dispersive x-ray, Auger electron, x-ray photoelectron and Raman spectroscopic analyses show that the particles and films are composed of amorphous carbon

  13. Down-regulation of voltage-dependent sodium channels initiated by sodium influx in developing neurons

    International Nuclear Information System (INIS)

    To address the issue of whether regulatory feedback exists between the electrical activity of a neuron and ion-channel density, the authors investigated the effect of Na+-channel activators (scorpion α toxin, batrachotoxin, and veratridine) on the density of Na+ channels in fetal rat brain neurons in vitro. A partial but rapid (t1/2, 15 min) disappearance of surface Na+ channels was observed as measured by a decrease in the specific binding of [3H]saxitoxin and 125I-labeled scorpion β toxin and a decrease in specific 22Na+ uptake. Moreover, the increase in the number of Na+ channels that normally occurs during neuronal maturation in vitro was inhibited by chronic channel activator treatment. The induced disappearance of Na+ channels was abolished by tetrodotoxin, was found to be dependent on the external Na+ concentration, and was prevented when either choline (a nonpermeant ion) or Li+ (a permeant ion) was substituted for Na+. Amphotericin B, a Na+ ionophore, and monensin were able to mimick the effect of Na+-channel activators, while a KCl depolarization failed to do this. This feedback regulation seems to be a neuronal property since Na+-channel density in cultured astrocytes was not affected by channel activator treatment or by amphotericin B. The present evidence suggests that an increase in intracellular Na+ concentration, whether elicited by Na+-channel activators or mediated by a Na+ ionophore, can induce a decrease in surface Na+ channels and therefore is involved in down-regulation of Na+-channel density in fetal rat brain neurons in vitro

  14. 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.

  15. 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

  16. Growth differentiation factor 8 down-regulates pentraxin 3 in human granulosa cells.

    Science.gov (United States)

    Chang, Hsun-Ming; Fang, Lanlan; Cheng, Jung-Chien; Klausen, Christian; Sun, Ying-Pu; Leung, Peter C K

    2015-03-15

    Growth differentiation factor 8 (GDF8), also known as myostatin, is highly expressed in the mammalian musculoskeletal system and plays critical roles in the regulation of skeletal muscle growth. Though not exclusively expressed in the musculoskeletal system, the expression and biological function of GDF8 has never been examined in the human ovary. Pentraxin 3 (PTX3) plays a key role in the assembly of extracellular matrix, which is essential for cumulus expansion, ovulation and in vivo fertilization. The aim of this study was to investigate GDF8 expression and function in human granulosa cells and to examine its underlying molecular determinants. An established immortalized human granulosa cell line (SVOG), granulosa cell tumor cell line (KGN) and primary granulosa-lutein cells were used as study models. We now demonstrate for the first time that GDF8 is expressed in human granulosa cells and follicular fluid. All 16 follicular fluid samples tested contained GDF8 protein at an average concentration of 3 ng/ml. In addition, GDF8 treatment significantly decreased PTX3 mRNA and protein levels. These suppressive effects, along with the induction of SMAD2/3 phosphorylation, were abolished by co-treatment with the ALK4/5/7 inhibitor SB431542. Knockdown of ALK5, ACVR2A/ACVR2B or SMAD4 reversed the effects of GDF8-induced PTX3 suppression. These results indicate that GDF8 down-regulates PTX3 expression via ACVR2A/ACVR2B-ALK5-mediated SMAD-dependent signaling in human granulosa cells. These novel findings support a potential role for GDF8 in the regulation of follicular function, likely via autocrine effects on human granulosa cells. PMID:25641196

  17. 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.

  18. 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.

  19. 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.

  20. Irradiation of protoporphyric mice induces down-regulation of epidermal eicosanoid metabolism

    International Nuclear Information System (INIS)

    This study investigated the effect of radiation on clinical and histologic changes, and on cutaneous eicosanoid metabolism, in Skh:HR-1 hairless albino mice rendered protoporphyric by the administration of collidine. At 0.1-18 h after exposure to 12 kJ/m2 of 396-406 nm irradiation, thicknesses of back skin and ears were measured, and histologic changes were evaluated by using hematoxylin and eosin (H-E) and Giemsa's stains. Activities of eicosanoid-metabolizing enzymes in epidermal and dermal homogenates were assessed by incubating the tissue homogenates with 3H-AA, followed by quantitation of the eicosanoids generated by radio-TLC. In irradiated protoporphyric mice, an increase of back-skin thickness was noted at 0.1 h, reaching a peak at 18 h, whereas maximal increase in ear thickness was observed at 12 h. Histologic changes included dermal edema, increased mast cell degranulation, and mononuclear cells in the dermis. In these irradiated protoporphyric animals, generations of 6 keto-PGF1a, PGF2a, PGE2, PGD2, and HETE by epidermal eicosanoid-metabolizing enzymes were markedly suppressed at all the timepoints studied. Dermal eicosanoid-metabolizing enzymes of irradiated protoporphyric mice generated increased amounts of PGE2 and HETE at 18 h, probably reflecting the presence of dermal cellular infiltrates. The suppression of the activities of epidermal eicosanoid-metabolizing enzymes was prevented by intraperitoneal injection of WR-2721, a sulfhydryl group generator, prior to irradiation, suggesting that the suppression was secondary to photo-oxidative damage of the enzymes during the in vivo phototoxic response. These results suggest that the effect of protoporphyrin and radiation on cutaneous eicosanoid metabolism in this animal model in vivo is that of a down regulation of the activities of epidermal eicosanoid-metabolizing enzymes

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

    Directory of Open Access Journals (Sweden)

    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.

  3. Eugenol triggers apoptosis in breast cancer cells through E2F1/survivin down-regulation

    International Nuclear Information System (INIS)

    Breast cancer is a major health problem that threatens the lives of millions of women worldwide each year. Most of the chemotherapeutic agents that are currently used to treat this complex disease are highly toxic with long-term side effects. Therefore, novel generation of anti-cancer drugs with higher efficiency and specificity are urgently needed. Breast cancer cell lines were treated with eugenol and cytotoxicity was measured using the WST-1 reagent, while propidium iodide/annexinV associated with flow cytometry was utilized in order to determine the induced cell death pathway. The effect of eugenol on apoptotic and pro-carcinogenic proteins, both in vitro and in tumor xenografts was assessed by immunoblotting. While RT-PCR was used to determine eugenol effect on the E2F1 and survivin mRNA levels. In addition, we tested the effect of eugenol on cell proliferation using the real-time cell electronic sensing system. Eugenol at low dose (2 μM) has specific toxicity against different breast cancer cells. This killing effect was mediated mainly through inducing the internal apoptotic pathway and strong down-regulation of E2F1 and its downstream antiapoptosis target survivin, independently of the status of p53 and ERα. Eugenol inhibited also several other breast cancer related oncogenes, such as NF-κB and cyclin D1. Moreover, eugenol up-regulated the versatile cyclin-dependent kinase inhibitor p21WAF1 protein, and inhibited the proliferation of breast cancer cells in a p53-independent manner. Importantly, these anti-proliferative and pro-apoptotic effects were also observed in vivo in xenografted human breast tumors. Eugenol exhibits anti-breast cancer properties both in vitro and in vivo, indicating that it could be used to consolidate the adjuvant treatment of breast cancer through targeting the E2F1/survivin pathway, especially for the less responsive triple-negative subtype of the disease

  4. 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

  5. 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.

  6. 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

  7. 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.

  8. Synthesis of Graphenic Carbon Materials on Nickel Particles with Controlled Quantity of Carbon

    Science.gov (United States)

    Grehov, V.; Kalnacs, J.; Mishnev, A.; Kundzins, K.

    2016-02-01

    A cheap, comparatively simple and effective method is proposed for the large quantity production of the sheets of graphenic carbon materials (GCM) by annealing the mixture of nickel powder with a suitable carbon amount at the temperatures close to 1000 ºC. The number of graphene layers in the sheets of GCM may be varied by altering the amount of carbon in the mixture and parameters of annealing and drying of the obtained products. Samples of GCM were prepared in the form of heat-dried GCM paper and in the form of graphene sponge with freeze-drying. The appearance of GCM on the surface of Ni particles was identified using a scanning electron microscope (SEM) at a low accelerating voltage of 5 kV. The thickness and properties of the layers were investigated by electron microscopy and X-ray diffraction. The fabrication processes were carried out at the concentrations of added carbon from 0 to 1 at%. The results obtained are fully consistent with the well-known solid phase reactions of carbon dissolution in Ni at 1000 °C and graphene or graphite precipitation on the surface with cooling down to the room temperatures.

  9. Synthesis of Graphenic Carbon Materials on Nickel Particles with Controlled Quantity of Carbon

    Directory of Open Access Journals (Sweden)

    Grehov V.

    2016-02-01

    Full Text Available A cheap, comparatively simple and effective method is proposed for the large quantity production of the sheets of graphenic carbon materials (GCM by annealing the mixture of nickel powder with a suitable carbon amount at the temperatures close to 1000 ºC. The number of graphene layers in the sheets of GCM may be varied by altering the amount of carbon in the mixture and parameters of annealing and drying of the obtained products. Samples of GCM were prepared in the form of heat-dried GCM paper and in the form of graphene sponge with freeze-drying. The appearance of GCM on the surface of Ni particles was identified using a scanning electron microscope (SEM at a low accelerating voltage of 5 kV. The thickness and properties of the layers were investigated by electron microscopy and X-ray diffraction. The fabrication processes were carried out at the concentrations of added carbon from 0 to 1 at%. The results obtained are fully consistent with the well-known solid phase reactions of carbon dissolution in Ni at 1000 °C and graphene or graphite precipitation on the surface with cooling down to the room temperatures.

  10. Carbon nanotubes for stabilization of nanostructured lipid particles

    Science.gov (United States)

    Gaunt, Nicholas P.; Patil-Sen, Yogita; Baker, Matthew J.; Kulkarni, Chandrashekhar V.

    2014-12-01

    Carbon nanotubes (CNTs) are increasingly studied for innovative biotechnological applications particularly where they are combined with essential biological materials like lipids. Lipids have been used earlier for enhancing the dispersibility of CNTs in aqueous solutions. Here we report a novel application of CNTs for stabilization of internally self-assembled nanostructured lipid particles of 2-5 μm size. Single-walled (pristine) as well as -OH and -COOH functionalized multi-walled CNTs were employed to produce nanostructured emulsions which stayed stable for months and could be re-dispersed after complete dehydration. Concentrations of CNTs employed for stabilization were very low; moreover CNTs were well-decorated with lipid molecules. These features contribute towards reducing their toxicity and improving biocompatibility for biomedical and pharmaceutical applications. Our approach paves the way for future development of combination therapies employing both CNTs and nanostructured lipid self-assembly together as carriers of different drugs.Carbon nanotubes (CNTs) are increasingly studied for innovative biotechnological applications particularly where they are combined with essential biological materials like lipids. Lipids have been used earlier for enhancing the dispersibility of CNTs in aqueous solutions. Here we report a novel application of CNTs for stabilization of internally self-assembled nanostructured lipid particles of 2-5 μm size. Single-walled (pristine) as well as -OH and -COOH functionalized multi-walled CNTs were employed to produce nanostructured emulsions which stayed stable for months and could be re-dispersed after complete dehydration. Concentrations of CNTs employed for stabilization were very low; moreover CNTs were well-decorated with lipid molecules. These features contribute towards reducing their toxicity and improving biocompatibility for biomedical and pharmaceutical applications. Our approach paves the way for future development

  11. 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

  12. 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

    oxygen species or anticancer drugs. Their elevated expressions facilitate cells to survive in stress circumstances. The HSP27 expression is enhanced in many tumor cells, implying that it is involved in tumor progression and the development of treatment resistance in various tumors, including lung cancer...... HSP27 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...

  13. 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.

  14. 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.

  15. Tissue-specific down-regulation of RIPK 2 in Mycobacterium leprae-infected nu/nu mice

    Directory of Open Access Journals (Sweden)

    Gue-Tae Chae

    1992-01-01

    Full Text Available RIPK 2 is adapter molecule in the signal pathway involved in Toll-like receptors. However, there has been no reported association between receptor-interacting serine/threonine kinase 2 (RIPK 2 expression and the infectious diseases involving mycobacterial infection. This study found that its expression was down-regulated in the footpads and skin but was up-regulated in the liver of Mycobacterium leprae-infected nu/nu mice compared with those of the M. leprae non-infected nu/nu mice. It was observed that the interlukin-12p40 and interferon-γ genes involved in the susceptibility of M. leprae were down-regulated in the skin but were up-regulated in the liver. Overall, this suggests that regulation of RIPK 2 expression is tissue-specifically associated with M. leprae infection.

  16. 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

    , 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<0.......05). Culture of coronary arteries for 48 h induced down-regulation of the angiotensin AT1 and AT2 receptor mRNA levels and also a less efficacious angiotensin II-induced vasoconstriction (Emax=103+/-2% before and 23+/-7% after artery culture, P<0.001). Artery culture may thus be a suitable method for studying...

  17. 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...

  18. 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...

  19. 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

  20. 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.

  1. 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

  2. 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.

  3. 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

  4. 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

  5. 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.

  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. Sensitization of multidrug-resistant human cancer cells to Hsp90 inhibitors by down-regulation of SIRT1

    Science.gov (United States)

    Kim, Hak-Bong; Lee, Su-Hoon; Um, Jee-Hyun; Oh, Won Keun; Kim, Dong-Wan; Kang, Chi-Dug; Kim, Sun-Hee

    2015-01-01

    The effectiveness of Hsp90 inhibitors as anticancer agents was limited in multidrug-resistant (MDR) human cancer cells due to induction of heat shock proteins (Hsps) such as Hsp70/Hsp27 and P-glycoprotein (P-gp)-mediated efflux. In the present study, we showed that resistance to Hsp90 inhibitors of MDR human cancer cells could be overcome with SIRT1 inhibition. SIRT1 knock-down or SIRT1 inhibitors (amurensin G and EX527) effectively suppressed the resistance to Hsp90 inhibitors (17-AAG and AUY922) in several MDR variants of human lymphoblastic leukemia and human breast cancer cell lines. SIRT1 inhibition down-regulated the expression of heat shock factor 1 (HSF1) and subsequently Hsps and facilitated Hsp90 multichaperone complex disruption via hyperacetylation of Hsp90/Hsp70. These findings were followed by acceleration of ubiquitin ligase CHIP-mediated mutant p53 (mut p53) degradation and subsequent down-regulation of P-gp in 17-AAG-treated MDR cancer cells expressing P-gp and mut p53 after inhibition of SIRT1. Therefore, combined treatment with Hsp90 inhibitor and SIRT1 inhibitor could be a more effective therapeutic approach for Hsp90 inhibitor-resistant MDR cells via down-regulation of HSF1/Hsps, mut p53 and P-gp. PMID:26416354

  8. Process to minimize cracking of pyrolytic carbon coatings on nuclear fuel particles

    International Nuclear Information System (INIS)

    A process for producing nuclear fuel particles is described in which microspheroidal particles of a fissile or fertile nuclear material are coated at an elevated temperature with a carbon buffer layer and a dense pyrolytic carbon layer and the coated particles are annealed immediately after coating at a temperature within the range of 1600 to 20000C, for about 30 minutes to relieve stresses produced during the coating process. (author)

  9. 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

  10. 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....

  11. Particles of spilled oil-absorbing carbon in contact with water

    Science.gov (United States)

    Muradov, Nazim

    2011-03-29

    Hydrogen generator coupled to or integrated with a fuel cell for portable power applications. Hydrogen is produced via thermocatalytic decomposition (cracking, pyrolysis) of hydrocarbon fuels in oxidant-free environment. The apparatus can utilize a variety of hydrocarbon fuels, including natural gas, propane, gasoline, kerosene, diesel fuel, crude oil (including sulfurous fuels). The hydrogen-rich gas produced is free of carbon oxides or other reactive impurities, so it could be directly fed to any type of a fuel cell. The catalysts for hydrogen production in the apparatus are carbon-based or metal-based materials and doped, if necessary, with a sulfur-capturing agent. Additionally disclosed are two novel processes for the production of two types of carbon filaments, and a novel filamentous carbon product. Carbon particles with surface filaments having a hydrophobic property of oil film absorption, compositions of matter containing those particles, and a system for using the carbon particles for cleaning oil spills.

  12. 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.

  13. 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...

  14. 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.

  15. 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

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. 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...

  1. 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.

  2. Down-regulation of SFRP1 as a putative tumor suppressor gene can contribute to human hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Hepatocellular carcinoma (HCC) is one of the most common cancers in the world. SFRP1 (the secreted frizzled-related protein 1), a putative tumor suppressor gene mapped onto chromosome 8p12-p11.1, the frequent loss of heterozygosity (LOH) region in human HCC, encodes a Wingless-type (Wnt) signaling antagonist and is frequently inactivated by promoter methylation in many human cancers. However, whether the down-regulation of SFRP1 can contribute to hepatocarcinogenesis still remains unclear. We investigated the expression of SFRP1 through real time RT-PCR and immunohistochemistry staining. The cell growth and colony formation were observed as the overexpression and knockdown of SFRP1. The DNA methylation status within SFRP1 promoter was analyzed through methylation-specific PCR or bisulphate-treated DNA sequencing assays. Loss of heterozygosity was here detected with microsatellite markers. SFRP1 was significantly down-regulated in 76.1% (35/46) HCC specimens at mRNA level and in 30% (30/100) HCCs indicated by immunohistochemistry staining, as compared to adjacent non-cancerous livers. The overexpression of SFRP1 can significantly inhibit the cell growth and colony formation of YY-8103, SMMC7721, and Hep3B cells. The RNA interference against the constitutional SFRP1 in the offspring SMMC7721 cells, which were stably transfected by ectopic SFRP1, can markedly promote cell growth of these cells. LOH of both microsatellite markers D8S532 and D8SAC016868 flanking the gene locus was found in 13% (6 of 46 HCCs) and 6.5% (3 of 46 HCCs) of the informative cases, respectively, where 5 of 8 HCC specimens with LOH showed the down-regulation of SFRP1. DNA hypermethylation within SFRP1 promoter was identified in two of three HCC specimens without SFRP1 expression. Moreover, the DNA methylation of SFRP1 promoter was significantly reduced, along with the re-expression of the gene, in those HCC cell lines, Bel7404, QGY7701, and MHCC-H, as treated by DAC. Our data suggested that the

  3. 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...

  4. 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

  5. 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...

  6. 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...

  7. Laser-induced breakdown spectroscopy (LIBS) for carbon single shot analysis of micrometer-sized particles

    International Nuclear Information System (INIS)

    The purpose of this work is to study the ability of the laser-induced breakdown spectroscopy (LIBS) technique to perform in situ (without sample preparation) detection of graphite particles circulating in a gas loop used to simulate the cooling gas circuit of a helium-cooled nuclear reactor. Results obtained with a laboratory scale set up are presented. The experiments were performed in nitrogen with micrometer-sized particles containing carbon (glucose particles and sodium hydrogeno-carbonate particles). Statistical shot to shot analysis was used to determine the concentration of the analyte. The variation of LIBS signal as a function of glucose particle diameter showed an underestimation of the signal of particles of diameters larger than 5 μm. This phenomenon is likely to be correlated to an incomplete vaporization in the laser-induced plasma of particles of sizes above 5 μm. Analytical measurements were performed with glucose particles and sodium hydrogeno-carbonate particles, and the concentration-based limit of detection of carbon was evaluated to be about 60 μg m-3. (authors)

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

    OpenAIRE

    Wittmaack, K.

    2005-01-01

    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 o...

  9. 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.

  10. Multinuclear giant cell formation is enhanced by down-regulation of Wnt signaling in gastric cancer cell line, AGS

    International Nuclear Information System (INIS)

    AGS cells, which were derived from malignant gastric adenocarcinoma tissue, lack E-cadherin-mediated cell adhesion but have a high level of nuclear β-catenin, which suggests altered Wnt signal. In addition, approximately 5% of AGS cells form multinuclear giant cells in the routine culture conditions, while taxol treatment causes most AGS cells to become giant cells. The observation of reduced nuclear β-catenin levels in giant cells induced by taxol treatment prompted us to investigate the relationship between Wnt signaling and giant cell formation. After overnight serum starvation, the shape of AGS cells became flattened, and this morphological change was accompanied by decrease in Myc expression and an increase in the giant cell population. Lithium chloride treatment, which inhibits GSK3β activity, reversed these serum starvation effects, which suggests an inverse relationship between Wnt signaling and giant cell formation. Furthermore, the down-regulation of Wnt signaling caused by the over-expression of ICAT, E-cadherin, and Axin enhanced giant cell formation. Therefore, down-regulation of Wnt signaling may be related to giant cell formation, which is considered to be a survival mechanism against induced cell death

  11. 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.

  12. Down-regulation of protein kinase C protects cerebellar granule neurons in primary culture from glutamate-induced neuronal death

    International Nuclear Information System (INIS)

    Exposing primary cultures of cerebellar granule neurons to 100 nM phorbol 12-myristate 13-acetate (PMA) for 24 hr decreases the Ca2+/phosphatidylserine/diolein-dependent protein kinase C. Immunoblot analysis of the homogenates with polyclonal antibodies raised against either the β-type PKC peptide or total rat brain PKC reveals a virtual loss of 78-kDa PKC immunoreactivity in the supernatant and marked decrease of PKC immunoreactivity in the pellet. Exposure of the cultures to 50 μM glutamate for 15 min (no Mg2+) induces the translocation of supernatant PKC immunoreactivity to the pellet. PMA-induced down-regulation of PKC decreases glutamate-elicited neurotoxicity. Yet, the culture exposure to 100 nM PMA fails to decrease the high-affinity binding of [3H]glutamate to neuronal membranes and does not reduce glutamate-induced activation of ionotropic or metabolotropic receptors (assayed as total membrane current measured in whole-cell voltage-clamped neurons, 45Ca2+ uptake in intact monolayers, inositolphospholipid hydrolysis, and transcriptional activation and translation of c-fos mRNA). On the other hand, PMA-induced PKC down-regulation reduces any increase in 45Ca2+ uptake or Ca2+-dependent proteolysis after glutamate withdrawal. These results support the view that PKC translocation is operative in glutamate-induced destabilization of cytosolic ionized Ca2+ homeostasis and neuronal death

  13. 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.

  14. 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.

  15. Down-regulation of 3H-imipramine binding sites in rat cerebral cortex prenatal exposure to antidepressants

    International Nuclear Information System (INIS)

    Several antidepressant drugs were given to pregnant rats in the last 15 days of gestation and 3H-imipramine binding (3H-IMI) was subsequently measured in the cerebral cortex of the offspring. The selective serotonin (5-HT) uptake blockers chlorimipramine and fluoxetine as well as the selective monoamine oxidase (MAO) inhibitors clorgyline and deprenyl induced, after prenatal exposure, a down-regulation of 3H-IMI binding sites at postnatal day 25. The density of these binding sites was still reduced at postnatal day 90 in rats exposed in utero to the MAO inhibitors. The antidepressants desipramine and nomifensine were ineffective in this respect. After chronic treatment of adult animals, only chlorimipramine was able to down-regulate the 3H-IMI binding sites. Consequently, prenatal exposure of rats to different antidepressant drugs affecting predominantly the 5-HT systems induces more marked and long-lasting effects on cortical 3H-IMI binding sites. The results suggest that the developing brain is more susceptible to the actions of antidepressants

  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. 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.

  19. 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.

  20. 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.

  1. 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.

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

    International Nuclear Information System (INIS)

    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

  3. 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 ...

  4. 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...

  5. Expression of Fragaria vesca PIP Aquaporins in Response to Drought Stress: PIP Down-Regulation Correlates with the Decline in Substrate Moisture Content

    OpenAIRE

    Šurbanovski, Nada; Sargent, Daniel J.; Else, Mark A.; Simpson, David W; Zhang, Hanma; Grant, Olga M.

    2013-01-01

    PIP aquaporin responses to drought stress can vary considerably depending on the isoform, tissue, species or level of stress; however, a general down-regulation of these genes is thought to help reduce water loss and prevent backflow of water to the drying soil. It has been suggested therefore, that it may be necessary for the plant to limit aquaporin production during drought stress, but it is unknown whether aquaporin down-regulation is gradual or triggered by a particular intensity of the ...

  6. 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...

  7. Influence of acid functionalization on the cardiopulmonary toxicity of carbon nanotubes and carbon black particles in mice

    International Nuclear Information System (INIS)

    Engineered carbon nanotubes are being developed for a wide range of industrial and medical applications. Because of their unique properties, nanotubes can impose potentially toxic effects, particularly if they have been modified to express functionally reactive chemical groups on their surface. The present study was designed to evaluate whether acid functionalization (AF) enhanced the cardiopulmonary toxicity of single-walled carbon nanotubes (SWCNT) as well as control carbon black particles. Mice were exposed by oropharyngeal aspiration to 10 or 40 μg of saline-suspended single-walled carbon nanotubes (SWCNTs), acid-functionalized SWCNTs (AF-SWCNTs), ultrafine carbon black (UFCB), AF-UFCB, or 2 μg LPS. 24 hours later, pulmonary inflammatory responses and cardiac effects were assessed by bronchoalveolar lavage and isolated cardiac perfusion respectively, and compared to saline or LPS-instilled animals. Additional mice were assessed for histological changes in lung and heart. Instillation of 40 μg of AF-SWCNTs, UFCB and AF-UFCB increased percentage of pulmonary neutrophils. No significant effects were observed at the lower particle concentration. Sporadic clumps of particles from each treatment group were observed in the small airways and interstitial areas of the lungs according to particle dose. Patches of cellular infiltration and edema in both the small airways and in the interstitium were also observed in the high dose group. Isolated perfused hearts from mice exposed to 40 μg of AF-SWCNTs had significantly lower cardiac functional recovery, greater infarct size, and higher coronary flow rate than other particle-exposed animals and controls, and also exhibited signs of focal cardiac myofiber degeneration. No particles were detected in heart tissue under light microscopy. This study indicates that while acid functionalization increases the pulmonary toxicity of both UFCB and SWCNTs, this treatment caused cardiac effects only with the AF-carbon nanotubes

  8. 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...

  9. 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.

  10. 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...

  11. 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.

  12. Synthesis of diamondlike carbon particles in/on a water substrate by laser irradiation

    International Nuclear Information System (INIS)

    We proposed two-particle synthesis techniques using a liquid as a substrate. First, utilizing liquid instead of solid substrates, particle synthesis is expected on the liquid surface. Particles sink into the liquid before the particles grow into film, because of liquid fluidity. Second, the excitation of a gas dissolved in water was also attempted. An ArF excimer laser beam was focused in a chamber. The 60% volume of the chamber was filled with water, in which methane was dissolved and the remaining space of the chamber was filled with methane gas. As a result, diamondlike carbon particles could be synthesized in water. The particles synthesized from methane in the gas phase were 50-200 nm in diameter, and the particles synthesized from methane dissolved in water were 200-700 nm in diameter, and no structural differences were observed between the particles of two different diameters. Energy-dispersive spectroscopy, Raman spectroscopy analysis, and high-resolution transmission electron microscopy observations revealed that particles contained a diamondlike carbon component and that graphite was attached to them. These particles were harder than graphite particles

  13. STAT5 proteins are involved in down-regulation of iron regulatory protein 1 gene expression by nitric oxide.

    Science.gov (United States)

    Starzynski, Rafal Radoslaw; Gonçalves, Ana Sofia; Muzeau, Françoise; Tyrolczyk, Zofia; Smuda, Ewa; Drapier, Jean-Claude; Beaumont, Carole; Lipinski, Pawel

    2006-12-01

    RNA-binding activity of IRP1 (iron regulatory protein 1) is regulated by the insertion/extrusion of a [4Fe-4S] cluster into/from the IRP1 molecule. NO (nitic oxide), whose ability to activate IRP1 by removing its [4Fe-4S] cluster is well known, has also been shown to down-regulate expression of the IRP1 gene. In the present study, we examine whether this regulation occurs at the transcriptional level. Analysis of the mouse IRP1 promoter sequence revealed two conserved putative binding sites for transcription factor(s) regulated by NO and/or changes in intracellular iron level: Sp1 (promoter-selective transcription factor 1) and MTF1 (metal transcription factor 1), plus GAS (interferon-gamma-activated sequence), a binding site for STAT (signal transducer and activator of transcription) proteins. In order to define the functional activity of these sequences, reporter constructs were generated through the insertion of overlapping fragments of the mouse IRP1 promoter upstream of the luciferase gene. Transient expression assays following transfection of HuH7 cells with these plasmids revealed that while both the Sp1 and GAS sequences are involved in basal transcriptional activity of the IRP1 promoter, the role of the latter is predominant. Analysis of protein binding to these sequences in EMSAs (electrophoretic mobility-shift assays) using nuclear extracts from mouse RAW 264.7 macrophages stimulated to synthesize NO showed a significant decrease in the formation of Sp1-DNA and STAT-DNA complexes, compared with controls. We have also demonstrated that the GAS sequence is involved in NO-dependent down-regulation of IRP1 transcription. Further analysis revealed that levels of STAT5a and STAT5b in the nucleus and cytosol of NO-producing macrophages are substantially lower than in control cells. These findings provide evidence that STAT5 proteins play a role in NO-mediated down-regulation of IRP1 gene expression. PMID:16886906

  14. 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

  15. 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.

  16. 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)

  17. 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.

  18. 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...... KCNQ1 internalization and stability is physiologically regulated by its Nedd4/Nedd4-like-dependent ubiquitylation. This mechanism may thereby be important in regulating the surface density of the KCNQ1 channels in cardiomyocytes and other cell types....

  19. 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

  20. First pharmacophore-based identification of androgen receptor down-regulating agents: discovery of potent anti-prostate cancer agents.

    Science.gov (United States)

    Purushottamachar, Puranik; Khandelwal, Aakanksha; Chopra, Pankaj; Maheshwari, Neha; Gediya, Lalji K; Vasaitis, Tadas S; Bruno, Robert D; Clement, Omoshile O; Njar, Vincent C O

    2007-05-15

    A qualitative 3D pharmacophore model (a common feature based model or Catalyst HipHop algorithm) was developed for well-known natural product androgen receptor down-regulating agents (ARDAs). The four common chemical features identified included: one hydrophobic group, one ring aromatic group, and two hydrogen bond acceptors. This model served as a template in virtual screening of the Maybridge and NCI databases that resulted in identification of six new ARDAs (EC(50) values 17.5-212 microM). Five of these molecules strongly inhibited the growth of human prostate LNCaP cells. These novel compounds may be used as leads to develop other novel anti-prostate cancer agents. PMID:17383188

  1. 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.

  2. 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

  3. 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.

  4. 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.

  5. 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

  6. Reversible epigenetic down-regulation of MHC molecules by devil facial tumour disease illustrates immune escape by a contagious cancer.

    Science.gov (United States)

    Siddle, Hannah V; Kreiss, Alexandre; Tovar, Cesar; Yuen, Chun Kit; Cheng, Yuanyuan; Belov, Katherine; Swift, Kate; Pearse, Anne-Maree; Hamede, Rodrigo; Jones, Menna E; Skjødt, Karsten; Woods, Gregory M; Kaufman, Jim

    2013-03-26

    Contagious cancers that pass between individuals as an infectious cell line are highly unusual pathogens. Devil facial tumor disease (DFTD) is one such contagious cancer that emerged 16 y ago and is driving the Tasmanian devil to extinction. As both a pathogen and an allograft, DFTD cells should be rejected by the host-immune response, yet DFTD causes 100% mortality among infected devils with no apparent rejection of tumor cells. Why DFTD cells are not rejected has been a question of considerable confusion. Here, we show that DFTD cells do not express cell surface MHC molecules in vitro or in vivo, due to down-regulation of genes essential to the antigen-processing pathway, such as β2-microglobulin and transporters associated with antigen processing. Loss of gene expression is not due to structural mutations, but to regulatory changes including epigenetic deacetylation of histones. Consequently, MHC class I molecules can be restored to the surface of DFTD cells in vitro by using recombinant devil IFN-γ, which is associated with up-regulation of the MHC class II transactivator, a key transcription factor with deacetylase activity. Further, expression of MHC class I molecules by DFTD cells can occur in vivo during lymphocyte infiltration. These results explain why T cells do not target DFTD cells. We propose that MHC-positive or epigenetically modified DFTD cells may provide a vaccine to DFTD. In addition, we suggest that down-regulation of MHC molecules using regulatory mechanisms allows evolvability of transmissible cancers and could affect the evolutionary trajectory of DFTD. PMID:23479617

  7. 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.

  8. KIAA0101 (OEACT-1), an expressionally down-regulated and growth-inhibitory gene in human hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Our previous cDNA array results indicated KIAA0101 as one of the differentially expressed genes in human hepatocellular carcinoma (HCC) as compared with non-cancerous liver. However, it is necessary to study its expression at protein level in HCC and its biological function for HCC cell growth. Western blot and tissue array were performed to compare KIAA0101 protein expression level in paired human HCC and non-cancerous liver tissues from the same patients. Investigation of its subcellular localization was done by using dual fluorescence image examination and enriched mitochondrial protein Western blot analysis. The in vitro cell growth curve was used for examing the effect of over-expression of KIAA0101 in HCC cells. FACS was used to analyze the cell cycle pattern in KIAA0101 expression positive (+) and negative (-) cell populations isolated by the pMACSKKII system after KIAA0101 cDNA transfection. Western blot showed KIAA0101 protein expression was down-regulated in HCC tissues as compared with their counterpart non-cancerous liver tissues in 25 out of 30 cases. Tissue array also demonstrated the same pattern in 161 paired samples. KIAA0101 was predominantly localized in mitochondria and partially in nuclei. KIAA0101 cDNA transfection could inhibit the HCC cell growth in vitro. In cell cycle analysis, it could arrest cells at the G1 to S phase transition. KIAA0101 protein expression was down-regulated in HCC. This gene could inhibit the HCC cell growth in vitro and presumably by its blocking effect on cell cycle

  9. Curcumin Exerts its Anti-hypertensive Effect by Down-regulating the AT1 Receptor in Vascular Smooth Muscle Cells.

    Science.gov (United States)

    Yao, Yonggang; Wang, Wei; Li, Meixiang; Ren, Hongmei; Chen, Caiyu; Wang, Jialiang; Wang, Wei Eric; Yang, Jian; Zeng, Chunyu

    2016-01-01

    Curcumin exerts beneficial effects on cardiovascular diseases, including hypertension. However, its mechanisms are unknown. We propose that curcumin prevents the development of hypertension by regulating AT1 receptor (AT1R) expression in arteries. The present study examined how curcumin regulates AT1R expression in vascular smooth muscle cells and investigated the physiological significance of this regulation in angiotensin (Ang) II-induced hypertension. The results showed that curcumin decreased AT1R expression in a concentration- and time-dependent manner in vascular smooth muscle cells. Using luciferase reporters with an entire AT1 or a mutant AT1R in A10 cells, the AT1R promoter activity was inhibited by 10(-6 )M curcumin, and the proximal element (from -61 to +25 bp) of the AT1R promoter was crucial for curcumin-induced AT1R down-regulation. An electrophoretic mobility shift assay showed that curcumin decreased specificity protein 1 (SP1) binding with the AT1R promoter in A10 cells. Curcumin treatment reduced Ang II-induced hypertension in C57Bl/6J mice, which was accompanied by lower AT1R expression in the arteries and decreased Ang II-mediated vasoconstriction in the mesenteric artery. These findings indicate that curcumin down-regulates AT1R expression in A10 cells by affecting SP1/AT1R DNA binding, thus reducing AT1R-mediated vasoconstriction and subsequently prevents the development of hypertension in an Ang II-induced hypertensive model. PMID:27146402

  10. 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.

  11. Down-regulation of the inhibitor of growth family member 4 (ING4 in different forms of pulmonary fibrosis

    Directory of Open Access Journals (Sweden)

    Froudarakis Marios

    2009-02-01

    Full Text Available Abstract Background Recent evidence has underscored the role of hypoxia and angiogenesis in the pathogenesis of idiopathic fibrotic lung disease. Inhibitor of growth family member 4 (ING4 has recently attracted much attention as a tumor suppressor gene, due to its ability to inhibit cancer cell proliferation, migration and angiogenesis. The aim of our study was to investigate the role of ING4 in the pathogenesis of pulmonary fibrosis both in the bleomycin (BLM-model and in two different types of human pulmonary fibrosis, including idiopathic pulmonary fibrosis (IPF and cryptogenic organizing pneumonia (COP. Methods Experimental model of pulmonary fibrosis was induced by a single tail vein injection of bleomycin in 6- to 8-wk-old C57BL/6mice. Tissue microarrays coupled with qRT-PCR and immunohistochemistry were applied in whole lung samples and paraffin-embedded tissue sections of 30 patients with IPF, 20 with COP and 20 control subjects. Results A gradual decline of ING4 expression in both mRNA and protein levels was reported in the BLM-model. ING4 was also found down-regulated in IPF patients compared to COP and control subjects. Immunolocalization analyses revealed increased expression in areas of normal epithelium and in alveolar epithelium surrounding Masson bodies, in COP lung, whereas showed no expression within areas of active fibrosis within IPF and COP lung. In addition, ING4 expression levels were negatively correlated with pulmonary function parameters in IPF patients. Conclusion Our data suggest a potential role for ING4 in lung fibrogenesis. ING4 down-regulation may facilitate aberrant vascular remodelling and fibroblast proliferation and migration leading to progressive disease.

  12. Distribution of beta-adrenergic receptors in failing human myocardium. Implications for mechanisms of down-regulation

    International Nuclear Information System (INIS)

    The density of beta-adrenergic receptors is reduced in crude membranes prepared from failing human myocardium. We used quantitative autoradiography of radioligand binding sites in intact tissue slices to determine whether the total tissue content of receptors is reduced and to characterize the transmural distribution of receptors in cardiac myocytes and the coronary vasculature in hearts obtained from nine cardiac transplant patients with severe congestive failure. Binding of [125Iodo]cyanopindolol to transmural slices of human myocardium was rapid, saturable, stereoselective, and displaceable by agonists and antagonists with an appropriate rank order of potency. Binding isotherms in four normal and nine failing ventricles showed a significant reduction in the total tissue content of beta-receptors in failing myocardium (38.3 +/- 2.0 fmol/mg protein) compared with normal tissue (52.4 +/- 1.7 fmol/mg protein, p = 0.038). In the normal ventricles, the greatest receptor density was observed autoradiographically in myocytic regions of the subendocardium. Receptor density of the coronary arterioles was approximately 70% of that in adjacent myocytic regions. The density of binding sites in both myocytic regions and arterioles was diminished in all regions of the failing ventricles, but down-regulation was due primarily to a selective reduction of beta-receptors of subendocardial myocytes (63 +/- 5% of subepicardial receptor density vs. 115 +/- 6% in controls, p less than 0.0001). These observations indicate that down-regulation occurs nonuniformly in the transmural distribution and thus is likely not related simply to elevated circulating catecholamine levels

  13. 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.

  14. The transcription factor FOXO4 is down-regulated and inhibits tumor proliferation and metastasis in gastric cancer

    International Nuclear Information System (INIS)

    FOXO4, a member of the FOXO family of transcription factors, is currently the focus of intense study. Its role and function in gastric cancer have not been fully elucidated. The present study was aimed to investigate the expression profile of FOXO4 in gastric cancer and the effect of FOXO4 on cancer cell growth and metastasis. Immunohistochemistry, Western blotting and qRT-PCR were performed to detect the FOXO4 expression in gastric cancer cells and tissues. Cell biological assays, subcutaneous tumorigenicity and tail vein metastatic assay in combination with lentivirus construction were performed to detect the impact of FOXO4 to gastric cancer in proliferation and metastasis in vitro and in vivo. Confocal and qRT-PCR were performed to explore the mechanisms. We found that the expression of FOXO4 was decreased significantly in most gastric cancer tissues and in various human gastric cancer cell lines. Up-regulating FOXO4 inhibited the growth and metastasis of gastric cancer cell lines in vitro and led to dramatic attenuation of tumor growth, and liver and lung metastasis in vivo, whereas down-regulating FOXO4 with specific siRNAs promoted the growth and metastasis of gastric cancer cell lines. Furthermore, we found that up-regulating FOXO4 could induce significant G1 arrest and S phase reduction and down-regulation of the expression of vimentin. Our data suggest that loss of FOXO4 expression contributes to gastric cancer growth and metastasis, and it may serve as a potential therapeutic target for gastric cancer

  15. 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.

  16. Curcumin Exerts its Anti-hypertensive Effect by Down-regulating the AT1 Receptor in Vascular Smooth Muscle Cells

    Science.gov (United States)

    Yao, Yonggang; Wang, Wei; Li, Meixiang; Ren, Hongmei; Chen, Caiyu; Wang, Jialiang; Wang, Wei Eric; Yang, Jian; Zeng, Chunyu

    2016-01-01

    Curcumin exerts beneficial effects on cardiovascular diseases, including hypertension. However, its mechanisms are unknown. We propose that curcumin prevents the development of hypertension by regulating AT1 receptor (AT1R) expression in arteries. The present study examined how curcumin regulates AT1R expression in vascular smooth muscle cells and investigated the physiological significance of this regulation in angiotensin (Ang) II-induced hypertension. The results showed that curcumin decreased AT1R expression in a concentration- and time-dependent manner in vascular smooth muscle cells. Using luciferase reporters with an entire AT1 or a mutant AT1R in A10 cells, the AT1R promoter activity was inhibited by 10−6 M curcumin, and the proximal element (from −61 to +25 bp) of the AT1R promoter was crucial for curcumin-induced AT1R down-regulation. An electrophoretic mobility shift assay showed that curcumin decreased specificity protein 1 (SP1) binding with the AT1R promoter in A10 cells. Curcumin treatment reduced Ang II-induced hypertension in C57Bl/6J mice, which was accompanied by lower AT1R expression in the arteries and decreased Ang II-mediated vasoconstriction in the mesenteric artery. These findings indicate that curcumin down-regulates AT1R expression in A10 cells by affecting SP1/AT1R DNA binding, thus reducing AT1R-mediated vasoconstriction and subsequently prevents the development of hypertension in an Ang II-induced hypertensive model. PMID:27146402

  17. Production of carbon monoxide by charged particle deposition.

    Science.gov (United States)

    Green, A. E. S.; Sawada, T.; Edgar, B. C.; Uman, M. A.

    1973-01-01

    Recent studies of electron energy deposition in CO2 and CO based upon a large set of electron impact cross sections are utilized to estimate the telluric CO directly produced by various charged-particle deposition mechanisms. The mechanisms considered are (1) lightning, (2) cloud coronal discharges, (3) background radioactivity, (4) natural electrostatic discharges, (5) photoelectrons in the ionosphere, (6) auroral electrons, (7) auroral protons, (8) cosmic rays, and (9) solar wind. 'Ball park' estimates of the global CO production by each of these mechanisms are given. Apart from mechanisms 1, 2, and 5, all CO production mechanisms are estimated to be small compared to artificial sources. If, as appears to be the case, the hot oxygen atoms and ions and other atomic species immediately produced by these three charged-particle deposition mechanisms react rapidly with CO2 to produce CO, these mechanisms can readily lead to CO production levels in the multimegaton-per-year range.

  18. Evaluation of airborne particle emissions from commercial products containing carbon nanotubes

    International Nuclear Information System (INIS)

    The emission of the airborne particles from epoxy resin test sticks with different carbon nanotube (CNT) loadings and two commercial products were characterized while sanding with three grit sizes and three disk sander speeds. The total number concentrations, respirable mass concentrations, and particle size number/mass distributions of the emitted particles were measured using a condensation particle counter, an optical particle counter, and a scanning mobility particle sizer. The emitted particles were sampled on a polycarbonate filter and analyzed using electron microscopy. The highest number concentrations (arithmetic mean = 4,670 particles/cm3) were produced with coarse sandpaper, 2 % (by weight) CNT test sticks and medium disk sander speed, whereas the lowest number concentrations (arithmetic mean = 92 particles/cm3) were produced with medium sandpaper, 2 % CNT test sticks and slow disk sander speed. Respirable mass concentrations were the highest (arithmetic mean = 1.01 mg/m3) for fine sandpaper, 2 % CNT test sticks and medium disk sander speed and the lowest (arithmetic mean = 0.20 mg/m3) for medium sandpaper, 0 % CNT test sticks and medium disk sander speed. For CNT-epoxy samples, airborne particles were primarily micrometer-sized epoxy cores with CNT protrusions. No free CNTs were observed in airborne samples, except for tests conducted with 4 % CNT-epoxy. The number concentration, mass concentration, and size distribution of airborne particles generated when products containing CNTs are sanded depends on the conditions of sanding and the characteristics of the material being sanded.

  19. 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)

  20. 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.

  1. 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.

  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; Galsgaard, E D; Norstedt, G; Postel-Vinay, M C; Kelly, P A; Nielsen, Jens Høiriis

    1995-01-01

    The functional significance of growth hormone (GH) receptor (GHR) internalization is unknown; therefore, we have analyzed domains and individual amino acids in the cytoplasmic region of the rat GHR required for ligand-mediated receptor internalization, receptor down-regulation, and transcriptional...... signaling. When various mutated GHR cDNAs were transfected stably into Chinese hamster ovary cells or transiently into monkey kidney (COS-7) cells, internalization of the GHR was found to be dependent upon a domain located between amino acids 318 and 380. Mutational analysis of aromatic residues 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...

  3. Carbon Particles in Airway Macrophage as a Surrogate Marker in the Early Detection of Lung Diseases

    Directory of Open Access Journals (Sweden)

    R Patil

    2012-03-01

    Full Text Available Background: It has been shown that inhalation of carbonaceous particulate matter may impair lung function in children. Objective: Using the carbon content of airway macrophages as a marker of individual exposure to particulate matter derived from fossil fuel, we sought direct evidence for this association.Methods: 300 children from puffed rice industrial areas and 300 children from population living in green zone were selected randomly. Airway macrophages were obtained from healthy children through sputum induction, and the grading of ultrafine carbon particles in airway macrophages was measured. Pulmonary function was also measured by spirometry. Results: Pulmonary function tests showed that in industrial area 42.6% and 20.3% of children had moderate obstructive airway disease and restrictive airway disease, respectively. In the green zone area, 7% of children had obstructive airway disease and 6% had restrictive airway disease. Evaluation of airway macrophages for ultrafine carbon particles revealed that in industrial area there were ultrafine carbon particles of grade 2 in 23% of subjects and grade 3 in 8.33% of individuals with obstructive airway disease. In the green zone area, the rates were 1.67% and 0.7%, respectively. Conclusion: The study provides a first evidence of the strong association between air pollution and development of airway diseases. Carbon particles in the sputum can be used as a marker for air pollution.

  4. Effect of Inhaled Carbon Ultrafine Particles on Reactive Hyperemia in Healthy Human Subjects

    OpenAIRE

    Shah, Alpa P.; Pietropaoli, Anthony P.; Frasier, Lauren M.; Speers, Donna M.; Chalupa, David C.; Delehanty, Joseph M.; Huang, Li-shan; Utell, Mark J.; Frampton, Mark W

    2007-01-01

    Background Ultrafine particles (UFP) may contribute to the cardiovascular effects of exposure to particulate air pollution, partly because of their relatively efficient alveolar deposition and potential to enter the pulmonary vascular space. Objectives This study tested the hypothesis that inhalation of elemental carbon UFP alters systemic vascular function. Methods Sixteen healthy subjects (mean age, 26.9 ± 6.5 years) inhaled air or 50 μg/m3 elemental carbon UFP by mouthpiece for 2 hr, while...

  5. Carbon and nitrogen content of transparent exopolymer particles (TEP) in relation to their Alcian Blue adsorption

    OpenAIRE

    Engel, Anja; Passow, U.

    2001-01-01

    The carbon and nitrogen content of transparent exopolymer particles (TEP) was determined and related to the concentration of TEP as quantified by a colorimetrical method. TEP were produced in the laboratory from dissolved precursors by laminar or turbulent shear. Dissolved precursors were obtained by 0.2 µm filtration from diatom cultures, with or without nutrient reduction, and from natural diatom populations. The relationship between carbon and TEP was significant, linear and species-specif...

  6. 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.

  7. Elemental and organic carbon in flue gas particles of various wood combustion systems

    Energy Technology Data Exchange (ETDEWEB)

    Gaegauf, C.; Schmid, M.; Guentert, P.

    2005-12-15

    The airborne particulate matter (PM) in the environment is of ever increasing concern to authorities and the public. The major fractions of particles in wood combustion processes are in the size less than 1 micron, typically in the range of 30 to 300 nm. Of specific interest is the content of the elemental carbon (EC) and organic carbon (OC) in the particles since these substances are known for its particular potential as carcinogens. Various wood combustion systems have been analysed (wood chip boiler, pellet boiler, wood log boiler, wood stove and open fire). The sampling of the particles was done by mean of a multi-stage particle sizing sampler cascade impactor. The impactor classifies the particles collected according to their size. The 7 stages classify the particles between 0.4 and 9 microns aerodynamic diameter. The analytical method for determining the content of EC and OC in the particles is based on coulometry. The coulometer measures the conductivity of CO{sub 2} released by oxidation of EC in the samples at 650 {sup o}C. The OC content is determined by pyrolysis of the particle samples in helium atmosphere.

  8. 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.

  9. 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.

  10. 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...

  11. 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

  12. 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

  13. Promoter hypermethylation-induced transcriptional down-regulation of the gene MYCT1 in laryngeal squamous cell carcinoma

    International Nuclear Information System (INIS)

    MYCT1, previously named MTLC, is a novel candidate tumor suppressor gene. MYCT1 was cloned from laryngeal squamous cell cancer (LSCC) and has been found to be down-regulated in LSCC; however, the regulatory details have not been fully elucidated. Here, we sought to investigate the methylation status of the CpG islands of MYCT1 and mRNA levels by bisulfite-specific PCR (BSP) based on sequencing restriction enzyme digestion, reverse transcription and real-time quantitative polymerase chain reaction (RQ-PCR). The function of specific sites in the proximal promoter of MYCT1 in LSCC was measured by transient transfection, luciferase assays, electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation assay (ChIP). The results suggested hypermethylation of 12 CpG sites of the promoter in both laryngeal cancer tissues and the laryngeal cancer line Hep-2 cell. The hypermethylation of the site CGCG (−695 to −692), which has been identified as the c-Myc binding site, was identified in laryngeal cancer tissues (59/73) compared to paired mucosa (13/73); in addition, statistical analysis revealed that the methylation status of this site significantly correlated with cancer cell differentiation(p < 0.01). The mRNA level of MYCT1 increased in Hep-2 cells treated with 5-aza-C (p < 0.01). The luciferase activity from mutant transfectants pGL3-MYCT1m (−852/+12, mut-695-C > A, mut-693-C > G) was significantly reduced compared with the wild type pGL3-MYCT1 (−852/+12), while the luciferase activity from wild transfectants pGL3-MYCT1 (−852/+12) rose after 5-aza treatment in Hep-2 cells. Finally, EMSA and ChIP confirmed that the methylation of the CGCG (−695 to −692) site prevented c-Myc from binding of the site and demethylation treatment of the 5′ flanking region of MYCT1 by 5-aza induced the increased occupation of the core promoter by c-Myc (p < 0.01). In summary, this study concluded that hypermethylation contributed to the transcriptional down-regulation

  14. Down-regulation of the caffeic acid O-methyltransferase gene in switchgrass reveals a novel monolignol analog

    Directory of Open Access Journals (Sweden)

    Tschaplinski Timothy J

    2012-09-01

    Full Text Available Abstract Background Down-regulation of the caffeic acid 3-O-methyltransferase EC 2.1.1.68 (COMT gene in the lignin biosynthetic pathway of switchgrass (Panicum virgatum resulted in cell walls of transgenic plants releasing more constituent sugars after pretreatment by dilute acid and treatment with glycosyl hydrolases from an added enzyme preparation and from Clostridium thermocellum. Fermentation of both wild-type and transgenic switchgrass after milder hot water pretreatment with no water washing showed that only the transgenic switchgrass inhibited C. thermocellum. Gas chromatography–mass spectrometry (GCMS-based metabolomics were undertaken on cell wall aqueous extracts to determine the nature of the microbial inhibitors. Results GCMS confirmed the increased concentration of a number of phenolic acids and aldehydes that are known inhibitors of microbial fermentation. Metabolomic analyses of the transgenic biomass additionally revealed the presence of a novel monolignol-like metabolite, identified as trans-3, 4-dimethoxy-5-hydroxycinnamyl alcohol (iso-sinapyl alcohol in both non-pretreated, as well as hot water pretreated samples. iso-Sinapyl alcohol and its glucoside were subsequently generated by organic synthesis and the identity of natural and synthetic materials were confirmed by mass spectrometric and NMR analyses. The additional novel presence of iso-sinapic acid, iso-sinapyl aldehyde, and iso-syringin suggest the increased activity of a para-methyltransferase, concomitant with the reduced COMT activity, a strict meta-methyltransferase. Quantum chemical calculations were used to predict the most likely homodimeric lignans generated from dehydration reactions, but these products were not evident in plant samples. Conclusions Down-regulation of COMT activity in switchgrass resulted in the accumulation of previously undetected metabolites resembling sinapyl alcohol and its related metabolites, but that are derived from para

  15. Vpu-mediated CD4 down-regulation and degradation is conserved among highly divergent SIVcpz strains

    International Nuclear Information System (INIS)

    Human immunodeficiency virus type 1 (HIV-1) along with simian immunodeficiency viruses from chimpanzees (SIVcpz) and three species of Old World monkeys from the genus Cercopithecus have been shown to encode a Vpu protein. To date, the functional characterization of Vpu has been limited to a small number of subtype B and more recently subtype C Vpu proteins. Using a recently developed VpuEGFP reporter system, we have shown that the subtype B and C Vpus are capable of preventing CD4 from being expressed on the cell surface. Using the same reporter system, we report here on the expression and functional analysis of Vpu protein from four SIVcpz isolates (CAM13, ANT, TAN1, and GAB1). All four SIV Vpu fusion proteins were efficiently expressed and prevented CD4 expression on the cell surface and induced CD4 degradation. This was surprising as three of the SIVcpz Vpu fusion proteins had only one canonical casein kinase II (CK-II) site (CAM13, ANT, TAN1) while previous studies with laboratory adapted HXB2 had indicated that both CK-II sites were required for CD4 degradation. Both ANT and TAN1 Vpu sequences encoded five consecutive negatively charged amino acids residues following the only CKII site (SAIEEDEE for ANT; SGVEEDEE for TAN1). We thus explored the possibility that this stretch of negatively charged amino acids might substitute for the lack of second CK-II site. Substitution of the aspartic acid at position 61 and glutamic acid at position 63 in the SIVcpz ANT Vpu within with lysine residues abolished the ability of this protein to down-modulate cell surface expression of CD4. Similarly, change of a serine to an alanine residue following the single consensus CK-II site of the CAM13 Vpu (SGNESDGGEEE) abolished CD4-down-regulation, suggesting that this serine was phosphorylated in the absence of a canonical CK-II site. Our results indicate that the serine was required, suggesting that this serine was phosphorylated by CK-II or possibly another cellular kinase. Taken

  16. 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

    other pathway is dependent on protein kinase C (PKC)-mediated activation of the CD3 gamma di-leucine-based receptor-sorting motif. Previous studies have failed to demonstrate a connection between ligand- and PKC-induced TCR down-regulation. Thus, although an apparent paradox, the dogma has been that...... ligand- and PKC-induced TCR down-regulations are not interrelated. By analyses of a newly developed CD3 gamma-negative T cell variant, freshly isolated and PHA-activated PBMC, and a mouse T cell line, we challenged this dogma and demonstrate in this work that PKC activation and the CD3 gamma di...

  17. 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...

  18. 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.

  19. Removal of two waterborne pathogenic bacterial strains by activated carbon particles prior to and after charge modification.

    Science.gov (United States)

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

    2006-11-01

    Waterborne diseases constitute a threat to public health despite costly treatment measures aimed at removing pathogenic microorganisms from potable water supplies. This paper compared the removal of Raoultella terrigena ATCC 33257 and Escherichia coli ATCC 25922 by negatively and positively charged types of activated carbon particles. Both strains display bimodal negative zeta-potential distributions in stabilized water. Carbon particles were suspended to an equivalent external geometric surface area of 700 cm2 in 250 mL of a bacterial suspension, with shaking. Samples were taken after different durations for plate counting. Initial removal rates were less elevated for the positively charged carbon particle than expected, yielding the conclusion that bacterial adhesion under shaking is mass-transport limited. After 360 min, however, the log-reduction of the more negatively charged R. terrigena in suspension was largest for the positively charged carbon particles as compared with the negatively charged ones, although conditioning in ultrapure or tap water of positively charged carbon particles for 21 days eliminated the favorable effect of the positive charge due to counterion adsorption from the water. Removal of the less negatively charged E. coli was less affected by aging of the (positively charged) carbon particles, confirming the role of electrostatic interactions in bacterial removal by activated carbon particles. The microporous, negatively charged coconut carbon performed less than the mesoporous, positively charged carbon particle prior to conditioning but did not suffer from loss of effect after conditioning in ultrapure or tap water. PMID:17144313

  20. Beta particles sensitivity of an all-carbon detector

    International Nuclear Information System (INIS)

    The response of high quality polycrystalline diamond pixel detectors to 90Sr beta particles is reported. Laser induced surface graphitization was used to realize 36 conductive contacts with 1 mm×1 mm area each, pitch 1.2 mm, on one detector side whereas a 8 mm×8 mm large area graphite contact was realized on the other face for grounding or biasing. A proximity board was used to hold the matrix, the amplifiers and to bond nine pixels to test homogeneity of response among 36 detector pixels. Two configurations were used to test charge collection uniformity and signal dependence on voltage. Both configurations showed noise pedestal fitted with a Gaussian curve of 1150 equivalent electrons (1σ) and typical beta source particles spectrum. Reversing the bias polarity the pulse height distribution does not change and the saturation of most probable value of charge collection was observed around ±200 V (0.4 V/μm) with reasonable pixel response uniformity equal to a most probable value 1.28±0.05 fC. The charge collection efficiency (CCE) measurement was implemented using coincidence mode acquisition with an external trigger made by a commercial polycrystalline diamond slab. The detector shows a CCE=0.59 estimated using the 1 mm2 large graphite pixel. The information earned with this first prototype will be used to design the new board with amplifying electronics for reading all 36 pixels at a time and perform experiments with monochromatic high energy electrons

  1. 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....

  2. 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.

  3. RNA Interference based Approach to Down Regulate Osmoregulators of Whitefly (Bemisia tabaci): Potential Technology for the Control of Whitefly

    Science.gov (United States)

    Raza, Amir; Malik, Hassan Jamil; Shafiq, Muhammad; Amin, Imran; Scheffler, Jodi A.; Scheffler, Brian E.; Mansoor, Shahid

    2016-01-01

    Over the past decade RNA interference (RNAi) technology has emerged as a successful tool not only for functional genomics, but in planta expression of short interfering RNAs (siRNAs) that could offer great potential for insect pest management. The diet of insects feeding exclusively on phloem sieves contains water and sugars as main components, and the uptake of the liquid food greatly depends on the osmotic pressure within the insect body. Based on this physiological mechanism, transgenic plants of Nicotiana tabacum were generated expressing double stranded RNA (dsRNA) against both aquaporin (AQP) and a sucrase gene, alpha glucosidase (AGLU). These two genes are involved in osmotic pressure maintenance particularly in sap sucking insects, and the aim was to disrupt osmoregulation within the insect ultimately leading to mortality. Real time quantitative PCR (RT-qPCR) was performed to assess the suppression of gene expression in Bemisia tabaci (B. tabaci) and mortality was recorded during transgenic tobacco feeding bioassays. Feeding of insects on plants expressing dsRNA significantly reduced the transcript level of the target genes in B. tabaci after six days of feeding and more than 70% mortality was observed in B. tabaci fed on transgenic plants compared to the control plants. Our data shows that down-regulation of genes related to osmoregulation may find practical applications for the control of this important pest in cotton and other crops. PMID:27105353

  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. 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

  6. 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.

  7. Chronic stress down-regulates growth hormone gene expression in peripheral blood mononuclear cells of older adults.

    Science.gov (United States)

    Malarkey, W B; Wu, H; Cacioppo, J T; Malarkey, K L; Poehlmann, K M; Glaser, R; Kiecolt-Glaser, J K

    1996-08-01

    "Pituitary" peptides are produced in both endocrine and immune cells. Acute and chronic stress can alter pituitary peptide secretion and might also influence neuroendocrine gene expression in human immune cells. We reasoned that, in Alzheimer caregivers, the chronic stress of caregiving would impact on the sympathetic-adrenal-medullary and hypothalamicpituitary-adrenal axis possibly leading to alterations in GH mRNA in their peripheral blood mononuclear cells (PBMCs). Therefore, we evaluated 10 caregivers and 10 controls subjects using a math and speech stress protocol to determine their neuroendocrine profile and to evaluate any relationship with mononuclear cell GH mRNA levels simultaneously acquired and then evaluated by a quantitative competitive RT-PCR technique. We found a significant (pcaregivers. Plasma ACTH and norepinephrine levels were negatively correlated with GH mRNA levels, suggesting their possible role in the down-regulation of mononuclear cell GH gene expression. These observations support the hypothesis that experiences associated with caregiving alter the brain's autonomic nervous system and neuroendocrine control of the hypothalamic-pituitary axis. These and perhaps other influences may then produce altered GH gene expression in mononuclear cells of chronically stressed individuals. It is tempting to speculate that the decreased GH mRNA that we found in these chronically stressed caregivers was partially responsible for their poor response to influenza vaccine and their delayed wound healing. PMID:21153091

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

    Directory of Open Access Journals (Sweden)

    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.

  9. 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

  10. Morphine-induced desensitization and down-regulation at mu-receptors in 7315C pituitary tumor cells

    Energy Technology Data Exchange (ETDEWEB)

    Puttfarcken, P.S.; Cox, B.M. (Uniformed Services Univ. of the Health Sciences, Bethesda, MD (USA))

    1989-01-01

    Pituitary 7315c tumor cells maintained in culture were treated with varying concentrations of morphine from 10 nM to 300 {mu}M, for periods of five or forty-eight hours. The ability of the mu-opioid receptor agonist, DAMGO, to inhibit forskolin-stimulated adenylyl cyclase in washed membrane preparations from the treated cells was compared with its activity in membranes from cells incubated in the absence of added morphine. In the same membrane preparations, the number and affinity of mu-opioid receptors was estimated by measurements of ({sup 3}H)diprenorphine binding. After 5 hr of treatment with morphine concentrations of 100 nM or higher, a significant reduction in inhibition of adenylyl cyclase by DAMGO was observed. Little further loss of agonist activity was observed when the incubations were extended to 48 hr. After 5 hr of morphine treatment, there was no change in either the number of receptors, or their affinity for ({sup 3}H)diprenorphine. However after 48 hr of morphine treatment, greater than 25% reductions in receptor number were apparent with morphine pretreatment concentrations of 10 {mu}M or higher. These results suggest that opioid tolerance in this system is primarily associated with a reduced ability of agonist-occupied receptor to activate the effector system. Receptor down-regulation was not necessary for loss of agonist response, although a reduction in receptor number occurred after exposure to high concentrations of morphine for periods longer than 5hr.

  11. Morphine-induced desensitization and down-regulation at mu-receptors in 7315C pituitary tumor cells

    International Nuclear Information System (INIS)

    Pituitary 7315c tumor cells maintained in culture were treated with varying concentrations of morphine from 10 nM to 300 μM, for periods of five or forty-eight hours. The ability of the mu-opioid receptor agonist, DAMGO, to inhibit forskolin-stimulated adenylyl cyclase in washed membrane preparations from the treated cells was compared with its activity in membranes from cells incubated in the absence of added morphine. In the same membrane preparations, the number and affinity of mu-opioid receptors was estimated by measurements of [3H]diprenorphine binding. After 5 hr of treatment with morphine concentrations of 100 nM or higher, a significant reduction in inhibition of adenylyl cyclase by DAMGO was observed. Little further loss of agonist activity was observed when the incubations were extended to 48 hr. After 5 hr of morphine treatment, there was no change in either the number of receptors, or their affinity for [3H]diprenorphine. However after 48 hr of morphine treatment, greater than 25% reductions in receptor number were apparent with morphine pretreatment concentrations of 10 μM or higher. These results suggest that opioid tolerance in this system is primarily associated with a reduced ability of agonist-occupied receptor to activate the effector system. Receptor down-regulation was not necessary for loss of agonist response, although a reduction in receptor number occurred after exposure to high concentrations of morphine for periods longer than 5hr

  12. 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.

  13. Deletion and down-regulation of HRH4 gene in gastric carcinomas: a potential correlation with tumor progression.

    Directory of Open Access Journals (Sweden)

    Chao Zhang

    Full Text Available BACKGROUND: Histamine is an established growth factor for gastrointestinal malignancies. The effect of histamine is largely determined locally by the histamine receptor expression pattern. Histamine receptor H4 (HRH4, the newest member of the histamine receptor family, is positively expressed on the epithelium of the gastrointestinal tract, and its function remains to be elucidated. Previously, we reported the decreased expression of HRH4 in colorectal cancers and revealed its correlation with tumor proliferation. In the current study, we aimed to investigate the abnormalities of HRH4 gene in gastric carcinomas (GCs. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed H4R expression in collected GC samples by quantitative PCR, Western blot analysis, and immunostaining. Our results showed that the protein and mRNA levels of HRH4 were reduced in some GC samples, especially in advanced GC samples. Copy number decrease of HRH4 gene was observed (17.6%, 23 out of 131, which was closely correlated with the attenuated expression of H4R. In vitro studies, using gastric cancer cell lines, showed that the alteration of HRH4 expression on gastric cancer cells influences tumor growth upon exposure to histamine. CONCLUSIONS/SIGNIFICANCE: We show for the first time that deletion of HRH4 gene is present in GC cases and is closely correlated with attenuated gene expression. Down-regulation of HRH4 in gastric carcinomas plays a role in histamine-mediated growth control of GC cells.

  14. Specific binding of phorbol esters to Friend erythroleukemia cells--general properties, down regulation and relationship to cell differentiation

    International Nuclear Information System (INIS)

    Specific and saturable binding sites for [20-3H]phorbol 12,13-dibutyrate ([3H]PDBu) were demonstrated in tact Friend erythroleukemia cells (FELC), in which inducible erythroid differentiation is reversibly inhibited by phorbol esters. The binding of [3H]PDBu to intact cells was maximal within only 15 min of incubation at 37 degrees C, after which there was a gradual decrease; binding at 4 degrees C however, was alow process, requiring greater than 180 min for maximal binding. A Scatchard analysis showed that the dissociation constant for binding of [3H]PDBu is 8.3 nM; at saturation, approximately 1.75 x 10(5) molecules of [3H]PDBu are bound per cell. When FELC were induced to differentiate with 4mM hexameethylene bisacetamide (approximately 80% of cells were benzidine-positive), a slight decrease (10-20%) in the number of binding sites at saturation was seen, but the dissociation constant was not changed. When the cells were precultured with non-radioactive phorbol esters, a significant decrease in [3H]PDBu binding was observed, suggesting a homologous down regulation of phorbol ester receptors. Scatchard analysis indicated that the decrease in [3H]PDBu binding was due to a decrease in the number of binding sites and not to a change in affinity. Such specific phorbol ester binding sites might mediate a number of biochemical and biological effects of phorbol esters on FELC

  15. Nitric oxide metabolite concentrations in maternal plasma decrease during parturition: possible transient down-regulation of nitric oxide synthesis.

    Science.gov (United States)

    Nanno, H; Sagawa, N; Itoh, H; Matsumoto, T; Terakawa, K; Mori, T; Itoh, H; Nakao, K

    1998-06-01

    To elucidate the possible involvement of nitric oxide (NO) in parturition, we measured the maternal plasma concentrations of the NO metabolites, atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and guanosine 3',5'-cyclic phosphate (cGMP) in pregnant women at various gestational ages including those at vaginal and elective Caesarean deliveries. The plasma cGMP and NO metabolite concentrations at vaginal delivery were significantly lower than those of the pregnant women in the third trimester of pregnancy. These concentrations remained low until 4 h after delivery but returned 24 h after delivery to values similar to those of the non-pregnant women. Such suppressions of plasma cGMP and NO metabolite concentrations were not observed in the women who underwent elective Caesarean section before the onset of labour. Moreover, no significant changes were observed in the plasma ANP and BNP concentrations at the time of vaginal and Caesarean deliveries, except that a slight but significant elevation of the plasma ANP concentration was observed 1 h after Caesarean delivery. In conclusion, the plasma concentrations of cGMP and NO metabolites significantly decreased at vaginal delivery but not at Caesarean delivery. These changes were independent of the plasma ANP and BNP concentrations, suggesting the possible down-regulation of maternal NO synthesis during parturition. PMID:9665345

  16. Down-Regulation of TM29, a Tomato SEPALLATA Homolog, Causes Parthenocarpic Fruit Development and Floral Reversion1

    Science.gov (United States)

    Ampomah-Dwamena, Charles; Morris, Bret A.; Sutherland, Paul; Veit, Bruce; Yao, Jia-Long

    2002-01-01

    We have characterized the tomato (Lycopersicon esculentum Mill.) MADS box gene TM29 that shared a high amino acid sequence homology to the Arabidopsis SEP1, 2, and 3 (SEPALLATA1, 2, and 3) genes. TM29 showed similar expression profiles to SEP1, with accumulation of mRNA in the primordia of all four whorls of floral organs. In addition, TM29 mRNA was detected in inflorescence and vegetative meristems. To understand TM29 function, we produced transgenic tomato plants in which TM29 expression was down-regulated by either cosuppression or antisense techniques. These transgenic plants produced aberrant flowers with morphogenetic alterations in the organs of the inner three whorls. Petals and stamens were green rather than yellow, suggesting a partial conversion to a sepalloid identity. Stamens and ovaries were infertile, with the later developing into parthenocarpic fruit. Ectopic shoots with partially developed leaves and secondary flowers emerged from the fruit. These shoots resembled the primary transgenic flowers and continued to produce parthenocarpic fruit and additional ectopic shoots. Based on the temporal and spatial expression pattern and transgenic phenotypes, we propose that TM29 functions in floral organ development, fruit development, and maintenance of floral meristem identity in tomato. PMID:12376628

  17. Down-regulation of TM29, a tomato SEPALLATA homolog, causes parthenocarpic fruit development and floral reversion.

    Science.gov (United States)

    Ampomah-Dwamena, Charles; Morris, Bret A; Sutherland, Paul; Veit, Bruce; Yao, Jia-Long

    2002-10-01

    We have characterized the tomato (Lycopersicon esculentum Mill.) MADS box gene TM29 that shared a high amino acid sequence homology to the Arabidopsis SEP1, 2, and 3 (SEPALLATA1, 2, and 3) genes. TM29 showed similar expression profiles to SEP1, with accumulation of mRNA in the primordia of all four whorls of floral organs. In addition, TM29 mRNA was detected in inflorescence and vegetative meristems. To understand TM29 function, we produced transgenic tomato plants in which TM29 expression was down-regulated by either cosuppression or antisense techniques. These transgenic plants produced aberrant flowers with morphogenetic alterations in the organs of the inner three whorls. Petals and stamens were green rather than yellow, suggesting a partial conversion to a sepalloid identity. Stamens and ovaries were infertile, with the later developing into parthenocarpic fruit. Ectopic shoots with partially developed leaves and secondary flowers emerged from the fruit. These shoots resembled the primary transgenic flowers and continued to produce parthenocarpic fruit and additional ectopic shoots. Based on the temporal and spatial expression pattern and transgenic phenotypes, we propose that TM29 functions in floral organ development, fruit development, and maintenance of floral meristem identity in tomato. PMID:12376628

  18. 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.

  19. 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

  20. Down-regulation of the Caffeic acid O-methyltransferase Gene in Switchgrass Reveals a Novel Monolignol Analog

    Energy Technology Data Exchange (ETDEWEB)

    Tschaplinski, Timothy J [ORNL; Standaert, Robert F [ORNL; Engle, Nancy L [ORNL; Martin, Madhavi Z [ORNL; Sangha, Amandeep K [ORNL; Parks, Jerry M [ORNL; Smith, Jeremy C [ORNL; Samuel, Reichel [ORNL; Pu, Yunqiao [ORNL; Ragauskas, A J [Georgia Institute of Technology; Hamilton, Choo Yieng [ORNL; Fu, Chunxiang [Noble Foundation; Wang, Zeng-Yu [Noble Foundation; Davison, Brian H [ORNL; Dixon, Richard A [Noble Foundation; Mielenz, Jonathan R [ORNL

    2012-01-01

    Down-regulation of the caffeic acid 3-O-methyltransferase (COMT) gene in the lignin biosynthetic pathway of switchgrass (Panicum virgatum) resulted in cell walls of transgenic plants releasing more constituent sugars after pretreatment by dilute acid and treatment with glycosyl hydrolases from an added enzyme preparation and from Clostridium thermocellum. Fermentation of both wild-type and transgenic switchgrass after milder hot water pretreatment with no water washing showed that only the transgenic switchgrass inhibited C. thermocellum. Gas chromatography-mass spectrometry-based metabolomics were undertaken on cell wall aqueous extracts to determine the nature of the microbial inhibitors, confirming the increased concentration of a number of phenolic acids and aldehydes that are known inhibitors of fermentation. Metabolomic analyses of the transgenic biomass additionally revealed the presence of a novel monolignol-like metabolite, identified as trans-3, 4-dimethoxy-5-hydroxycinnamyl alcohol (iso-sinapyl alcohol) in both non-pretreated, as well as hot water pretreated samples. Although there was no indication that iso-sinapyl alcohol was integrated into the cell wall, diversion of substrates from sinapyl alcohol to free iso-sinapyl alcohol, its glucoside, and associated upstream lignin pathway changes, including increased phenolic aldehydes and acids, are associated with more facile cell wall deconstruction, and to the observed inhibitory effect on microbial growth.

  1. 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.

  2. 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.

  3. VEGFR3 Inhibition Chemosensitizes Ovarian Cancer Stemlike Cells through Down-Regulation of BRCA1 and BRCA2

    Directory of Open Access Journals (Sweden)

    Jaeyoung Lim

    2014-04-01

    Full Text Available In ovarian cancer, loss of BRCA gene expression in tumors is associated with improved response to chemotherapy and increased survival. A means to pharmacologically downregulate BRCA gene expression could improve the outcomes of patients with BRCA wild-type tumors. We report that vascular endothelial growth factor receptor 3 (VEGFR3 inhibition in ovarian cancer cells is associated with decreased levels of both BRCA1 and BRCA2. Inhibition of VEGFR3 in ovarian tumor cells was associated with growth arrest. CD133+ ovarian cancer stemlike cells were preferentially susceptible to VEGFR3-mediated growth inhibition. VEGFR3 inhibition–mediated down-regulation of BRCA gene expression reversed chemotherapy resistance and restored chemosensitivity in resistant cell lines in which a BRCA2 mutation had reverted to wild type. Finally, we demonstrate that tumor-associated macrophages are a primary source of VEGF-C in the tumor microenvironment. Our studies suggest that VEGFR3 inhibition may be a pharmacologic means to downregulate BRCA genes and improve the outcomes of patients with BRCA wild-type tumors.

  4. VEGFR3 Inhibition Chemosensitizes Ovarian Cancer Stemlike Cells through Down-Regulation of BRCA1 and BRCA212

    Science.gov (United States)

    Lim, Jaeyoung; Yang, Kun; Taylor-Harding, Barbie; Wiedemeyer, W. Ruprecht; Buckanovich, Ronald J.

    2014-01-01

    In ovarian cancer, loss of BRCA gene expression in tumors is associated with improved response to chemotherapy and increased survival. A means to pharmacologically downregulate BRCA gene expression could improve the outcomes of patients with BRCA wild-type tumors. We report that vascular endothelial growth factor receptor 3 (VEGFR3) inhibition in ovarian cancer cells is associated with decreased levels of both BRCA1 and BRCA2. Inhibition of VEGFR3 in ovarian tumor cells was associated with growth arrest. CD133+ ovarian cancer stemlike cells were preferentially susceptible to VEGFR3-mediated growth inhibition. VEGFR3 inhibition–mediated down-regulation of BRCA gene expression reversed chemotherapy resistance and restored chemosensitivity in resistant cell lines in which a BRCA2 mutation had reverted to wild type. Finally, we demonstrate that tumor-associated macrophages are a primary source of VEGF-C in the tumor microenvironment. Our studies suggest that VEGFR3 inhibition may be a pharmacologic means to downregulate BRCA genes and improve the outcomes of patients with BRCA wild-type tumors. PMID:24862760

  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. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  8. 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.

  9. RNA Interference based Approach to Down Regulate Osmoregulators of Whitefly (Bemisia tabaci): Potential Technology for the Control of Whitefly.

    Science.gov (United States)

    Raza, Amir; Malik, Hassan Jamil; Shafiq, Muhammad; Amin, Imran; Scheffler, Jodi A; Scheffler, Brian E; Mansoor, Shahid

    2016-01-01

    Over the past decade RNA interference (RNAi) technology has emerged as a successful tool not only for functional genomics, but in planta expression of short interfering RNAs (siRNAs) that could offer great potential for insect pest management. The diet of insects feeding exclusively on phloem sieves contains water and sugars as main components, and the uptake of the liquid food greatly depends on the osmotic pressure within the insect body. Based on this physiological mechanism, transgenic plants of Nicotiana tabacum were generated expressing double stranded RNA (dsRNA) against both aquaporin (AQP) and a sucrase gene, alpha glucosidase (AGLU). These two genes are involved in osmotic pressure maintenance particularly in sap sucking insects, and the aim was to disrupt osmoregulation within the insect ultimately leading to mortality. Real time quantitative PCR (RT-qPCR) was performed to assess the suppression of gene expression in Bemisia tabaci (B. tabaci) and mortality was recorded during transgenic tobacco feeding bioassays. Feeding of insects on plants expressing dsRNA significantly reduced the transcript level of the target genes in B. tabaci after six days of feeding and more than 70% mortality was observed in B. tabaci fed on transgenic plants compared to the control plants. Our data shows that down-regulation of genes related to osmoregulation may find practical applications for the control of this important pest in cotton and other crops. PMID:27105353

  10. 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

  11. 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.

  12. 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.

  13. Evaluation of cases treated with particle reirradiation using carbon ions or protons for recurrent tumors of the head and neck after photon radiotherapy or particle radiotherapy

    International Nuclear Information System (INIS)

    We evaluated efficacy and safety of particle reirradiation using carbon ions or protons for recurrent tumors of the head and neck after photon or particle radiotherapy retrospectively. Among 28 cases, 15 cases were recurrence after photon radiotherapy and 13 cases after particle radiotherapy. Statistical analyses revealed that photon cases showed significantly better progression-free survival than particle cases. Acute morbidities were acceptable, however, late morbidities were more frequent and severer compared to initial irradiation. Particle reirradiation for recurrent head and neck tumors after photon radiotherapy might be beneficial, however, it is not the case for recurrence after particle radiotherapy. (author)

  14. 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 ...

  15. Adsorption of NO2 on carbon aerosols particles at the low ppb-level

    International Nuclear Information System (INIS)

    The adsorption of NO2 at the low ppb-level (3-40 ppb) on carbon aerosol particles was investigated. A sticking coefficient of about 2.10-4 was found, similar to that in previous studies using radioactively labeled 13NO2. (author) 2 figs., 2 refs

  16. 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.

  17. 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...

  18. 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.

  19. The structural-phase state of iron-carbon coatings formed by the ultradispersed particles

    Energy Technology Data Exchange (ETDEWEB)

    Manakova, Irina A., E-mail: manakova@inp.kz; Ozernoy, Alexey N., E-mail: manakova@inp.kz; Tuleushev, Yuriy Zh., E-mail: manakova@inp.kz; Vereshchak, Mikhail F., E-mail: manakova@inp.kz; Volodin, Valeriy N., E-mail: manakova@inp.kz; Zhakanbayev, Yeldar A., E-mail: manakova@inp.kz [Institute of Nuclear Physics, 050032 Almaty (Kazakhstan)

    2014-10-27

    The methods of nuclear gamma-resonance spectroscopy, elemental microanalysis, and X-ray diffraction were used to study nanoscale coatings. The samples were prepared by magnetron sputtering of carbon and iron particles. They alternately were deposited on monocrystalline silicon or polycrystalline corundum substrate moving relative to the plasma flows in the form of sublayers with a thickness of less than 0.6 nm up to the total thickness of 150-500 nm. Solid solutions with the carbon concentrations of up to 7.5, 12.0, 17.6, and 23.9 at% were produced by co-precipitation of ultradispersed particles of iron and carbon. Using method of conversion electron Mössbauer spectroscopy, we detected the anisotropy of orientation of magnetic moments of iron atoms due to texturing of the formed coatings. The deviation of the crystallite orientation from the average value depends on the degree of carbonization. At 550°C, the pearlite eutectic α‐Fe(C)+Fe{sub 3}C is formed from the amorphous structure without formation of intermediate carbides. The relative content of cementite correlates with the amount of carbon in the coating. The formation of the solid solutions-alloys directly during the deposition process confirms the theory of thermal-fluctuation melting of small particles.

  20. The structural-phase state of iron-carbon coatings formed by the ultradispersed particles

    Science.gov (United States)

    Manakova, Irina A.; Ozernoy, Alexey N.; Tuleushev, Yuriy Zh.; Vereshchak, Mikhail F.; Volodin, Valeriy N.; Zhakanbayev, Yeldar A.

    2014-10-01

    The methods of nuclear gamma-resonance spectroscopy, elemental microanalysis, and X-ray diffraction were used to study nanoscale coatings. The samples were prepared by magnetron sputtering of carbon and iron particles. They alternately were deposited on monocrystalline silicon or polycrystalline corundum substrate moving relative to the plasma flows in the form of sublayers with a thickness of less than 0.6 nm up to the total thickness of 150-500 nm. Solid solutions with the carbon concentrations of up to 7.5, 12.0, 17.6, and 23.9 at% were produced by co-precipitation of ultradispersed particles of iron and carbon. Using method of conversion electron Mössbauer spectroscopy, we detected the anisotropy of orientation of magnetic moments of iron atoms due to texturing of the formed coatings. The deviation of the crystallite orientation from the average value depends on the degree of carbonization. At 550°C, the pearlite eutectic α- Fe ( C )+ Fe3C is formed from the amorphous structure without formation of intermediate carbides. The relative content of cementite correlates with the amount of carbon in the coating. The formation of the solid solutions-alloys directly during the deposition process confirms the theory of thermal-fluctuation melting of small particles.

  1. 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.

  2. Preliminary evidences of CCM operation and its down regulation in relation to increasing CO2 levels in natural phytoplankton assemblages from the coastal waters of Bay of Bengal

    Science.gov (United States)

    Biswas, Haimanti; Rahman Shaik, Aziz Ur; Bandyopadhyay, Debasmita

    2014-05-01

    Bay of Bengal (BoB), a low productive part of the North Indian Ocean, often possesses low CO2 levels in its surface water and diatoms dominate the phytoplankton communities. Virtually no studies are available from this area reporting how this diatom dominated phytoplankton community would respond any increase in dissolved CO2 levels either naturally or anthopogenically. In most of the marine phytoplankton, the inefficiency of the sole carbon fixing enzyme Rubisco necessitates the need of concentrating dissolved inorganic carbon (DIC) (mostly as HCO3) inside the cell in excess of the ambient water concentrations in order to maintain high rate of photosynthesis under low CO2 levels through an energy consuming carbon concentration mechanisms (CCMs). The ubiquitous enzyme carbonic anhydrase (CA) plays a vital role in CCMs by converting HCO3- to CO2 and usually utilizes the trace metal zinc (Zn) as a cofactor. However, it is evident in many marine phytoplankton species that with increasing external CO2 levels, CCMs can be down-regulated leading to energetic savings which can be reallocated to growth; although exceptions occur. Hence, in order to predict their responses to the projected changes, it is imperative to understand their carbon metabolism patterns. We have conducted a series of incubation experiments in microcosms with natural phytoplankton communities from the coastal waters of BoB under different CO2 levels. Our results revealed that the rate of net photosynthetic oxygen evolution and biomass build-up increased in response to increasing CO2 levels. The depletion in δ13CPOM values were more in the high CO2 treatments relative to the low CO2 treated cells (control), indicating that dissolved CO2 uptake was higher when CO2 levels were increased. When additional Zn was added to the low CO2 treated cells, net photosynthetic oxygen evolution rate was increased significantly than that of the untreated control. It is likely that upon the supply of Zn under low CO2

  3. 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...

  4. 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

  5. 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...

  6. Expression of Fragaria vesca PIP aquaporins in response to drought stress: PIP down-regulation correlates with the decline in substrate moisture content.

    Science.gov (United States)

    Šurbanovski, Nada; Sargent, Daniel J; Else, Mark A; Simpson, David W; Zhang, Hanma; Grant, Olga M

    2013-01-01

    PIP aquaporin responses to drought stress can vary considerably depending on the isoform, tissue, species or level of stress; however, a general down-regulation of these genes is thought to help reduce water loss and prevent backflow of water to the drying soil. It has been suggested therefore, that it may be necessary for the plant to limit aquaporin production during drought stress, but it is unknown whether aquaporin down-regulation is gradual or triggered by a particular intensity of the stress. In this study, ten Fragaria PIP genes were identified from the woodland strawberry (Fragaria vesca L.) genome sequence and characterised at the sequence level. The water relations of F. vesca were investigated and the effect of different intensities of drought stress on the expression of four PIP genes, as well as how drought stress influences their diurnal transcription was determined. PIP down-regulation in the root corresponded to the level of drought stress. Moreover, transcript abundance of two genes highly expressed in the root (FvPIP1;1 and FvPIP2;1) was strongly correlated to the decline in substrate moisture content. The amplitude of diurnal aquaporin expression in the leaves was down-regulated by drought without altering the pattern, but showing an intensity-dependent effect. The results show that transcription of PIP aquaporins can be fine-tuned with the environment in response to declining water availability. PMID:24086403

  7. 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...

  8. 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.

  9. 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.

  10. Metformin suppresses CYP1A1 and CYP1B1 expression in breast cancer cells by down-regulating aryl hydrocarbon receptor expression

    International Nuclear Information System (INIS)

    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

  11. 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

  12. 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.

  13. 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.

  14. 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

  15. 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

  16. 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

  17. Metformin reduces the endotoxin-induced down-regulation of apolipoprotein E gene expression in macrophages

    International Nuclear Information System (INIS)

    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

  18. 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

  19. Arsenic trioxide inhibits cancer stem-like cells via down-regulation of Gli1 in lung cancer

    Science.gov (United States)

    Chang, Ke-Jie; Yang, Meng-Hang; Zheng, Jin-Cheng; Li, Bing; Nie, Wei

    2016-01-01

    Cancer stem cells (CSCs) are responsible for the tumorigenesis and recurrence, so targeting CSCs is a potential effective method to cure cancers. Activated Hedgehog signaling pathway has been proved to be implicated in the maintenance of self-renewal of CSCs, and arsenic trioxide (As2O3) has been reported to inhibit Gli1, a key transcription factor of Hedgehog pathway. In this study, we evaluated whether As2O3 has inhibitory effects on cancer stem-like cells (CSLCs) in lung cancer and further explored the possible mechanism. CCK8 assay and colony formation assay were performed to demonstrate the ability of As2O3 to inhibit the growth of NCI-H460 and NCI-H446 cells, which represented non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), respectively. Tumor sphere formation assay was carried out to evaluate the effects of As2O3 on stem cell-like subpopulations. The expression of stem cell biomarkers CD133 and stem cell transcription factors such as Sox2 and Oct4 were detected. Moreover, the effects of As2O3 on expression of Gli1 and its target genes were observed. We found that As2O3 inhibited the cell proliferation and reduced the colony formation ability. Importantly, As2O3 decreased the formation of tumor spheres. The expression of stem cell biomarker CD133 and stem cell transcription factors such as Sox2 and Oct4 were markedly reduced by As2O3 treatment. Furthermore, As2O3 decreased the expression of Gli1, N-myc and GAS1. Our results suggested that As2O3 is a promising agent to inhibit CSLCs in lung cancer. In addition, the mechanism of CSLCs inhibition might involve Gli1 down-regulation.

  20. 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

  1. Zeranol Down-Regulates p53 Expression in Primary Cultured Human Breast Cancer Epithelial Cells through Epigenetic Modification

    Directory of Open Access Journals (Sweden)

    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.

  2. Foxa1 reduces lipid accumulation in human hepatocytes and is down-regulated in nonalcoholic fatty liver.

    Directory of Open Access Journals (Sweden)

    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.

  3. 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

  4. 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.

  5. β1-Adrenergic blocker bisoprolol reverses down-regulated ion channels in sinoatrial node of heart failure rats.

    Science.gov (United States)

    Du, Yuan; Zhang, Junbo; Xi, Yutao; Wu, Geru; Han, Ke; Huang, Xin; Ma, Aiqun; Wang, Tingzhong

    2016-06-01

    Bisoprolol, an antagonist of β1-adrenergic receptors, is effective in reducing the morbidity and mortality in patients with heart failure (HF). It has been found that HF is accompanied with dysfunction of the sinoatrial node (SAN). However, whether bisoprolol reverses the decreased SAN function in HF and how the relevant ion channels in SAN change were relatively less studied. SAN function and messenger RNA (mRNA) expression of sodium channels and hyperpolarization-activated cyclic nucleotide-gated (HCN) channel subunits were assessed in sham-operated rats, abdominal arterio-venous shunt (volume overload)-induced HF rats, and bisoprolol- treated HF rats. SAN cells of rats were isolated by laser capture microdissection. Quantitative real-time PCR analysis was used to quantify mRNA expression of sodium channels and HCN channel subunits in SAN. Intrinsic heart rate declined and sinus node recovery time prolonged in HF rats, indicating the suppressed SAN function, which could be improved by bisoprolol treatment. Nav1.1, Nav1.6, and HCN4 mRNA expressions were reduced in SAN in HF rats compared with that in control rats. Treatment with bisoprolol could reverse both the SAN function and the Nav1.1, Nav1.6, and HCN4 mRNA expression partially. These data indicated that bisoprolol is effective in HF treatment partially due to improved SAN function by reversing the down-regulation of sodium channels (Nav1.1 and Nav1.6) and HCN channel (HCN4) subunits in SAN in failing hearts. PMID:26995749

  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. Interactions with the young down-regulate adult olfactory neurogenesis and enhance the maturation of olfactory neuroblasts in sheep mothers.

    Directory of Open Access Journals (Sweden)

    Frédéric Levy

    2014-02-01

    Full Text Available New neurons are continuously added in the dentate gyrus and the olfactory bulb of mammalian brain. While numerous environmental factors controlling survival of newborn neurons have been extensively studied, regulation by social interactions is less documented. We addressed this question by investigating the influence of parturition and interactions with the young on neurogenesis in sheep mothers. Using Bromodeoxyuridine, a marker of cell division, in combination with markers of neuronal maturation, the percentage of neuroblasts and new mature neurons in the olfactory bulb and the dentate gyrus was compared between groups of parturient ewes which could interact or not with their lamb, and virgins. In addition, a morphological analysis was performed by measuring the dendritic arbor of neuroblasts in both structures. We showed that the post-partum period was associated with a decrease in olfactory and hippocampal adult neurogenesis. In the olfactory bulb, the suppressive effect on neuroblasts was dependent on interactions with the young whereas in the dentate gyrus the decrease in new mature neurons was associated with parturition. In addition, dendritic length and number of nodes of neuroblasts were significantly enhanced by interactions with the lamb in the olfactory bulb but not in the dentate gyrus. Because interactions with the young involved learning of the olfactory signature of the lamb, we hypothesize that this learning is associated with a down-regulation in olfactory neurogenesis and an enhancement of olfactory neuroblast maturation. Our assumption is that fewer new neurons decrease cell competition in the olfactory bulb and enhance maturation of those new neurons selected to participate in the learning of the young odor.

  8. 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.

  9. 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

  10. 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.

  11. Down-regulation of microRNA152 is associated with the diagnosis and prognosis of patients with osteosarcoma.

    Science.gov (United States)

    Wang, Nai-Guo; Wang, Da-Chuan; Tan, Bing-Yi; Wang, Feng; Yuan, Ze-Nong

    2015-01-01

    Potential values of microRNA152 (miR-152) as a serum diagnostic and prognostic biomarker have not been determined in human osteosarcoma. By detecting the expression of miR-152 among 80 osteosarcoma patients, 20 periostitis patients and 20 healthy individuals using qRT-PCR, we aimed to explore the clinical significance of miR-152 in osteosarcoma patients. The expression of miR-152 was significantly decreased in patients with osteosarcoma compared to patients with periostitis (P<0.01) and healthy controls (P<0.01). The relationship between clinicopathologic characteristics and miR-152 was analyzed by chi-square test. The outcome indicated that miR-152 might be linked with the development of osteosarcoma. Moreover, the receiver operating characteristic (ROC) curve was performed to estimate the diagnostic value of miR-152. The result demonstrated that miR-152 might be a promising diagnostic marker of osteosarcoma with an AUC of 0.956, combing with 92.5% specificity and 96.2% sensitivity. The relationship between miR-152 and overall survival of osteosarcoma patients was analyzed by Kaplan-Meier curve and log rank test. As a result, the survival time of patients with low miR-152 expression was significantly shorter than those with high miR-152 expression (P<0.001). Then Cox regression analysis was used to estimate the prognostic value of miR-152 in osteosarcoma. The outcomes showed that low miR-152 expression (P=0.004) might be a potential independent prognostic marker for osteosarcoma patients. These findings suggested that down-regulation of miR-152 could be considered as a predictor for diagnosis and prognosis of osteosarcoma patients. PMID:26464682

  12. 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.

  13. 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

  14. 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.

  15. 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

  16. 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.

  17. 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.

  18. Interactions with the young down-regulate adult olfactory neurogenesis and enhance the maturation of olfactory neuroblasts in sheep mothers.

    Science.gov (United States)

    Brus, Maïna; Meurisse, Maryse; Keller, Matthieu; Lévy, Frédéric

    2014-01-01

    New neurons are continuously added in the dentate gyrus (DG) and the olfactory bulb of mammalian brain. While numerous environmental factors controlling survival of newborn neurons have been extensively studied, regulation by social interactions is less documented. We addressed this question by investigating the influence of parturition and interactions with the young on neurogenesis in sheep mothers. Using Bromodeoxyuridine, a marker of cell division, in combination with markers of neuronal maturation, the percentage of neuroblasts and new mature neurons in the olfactory bulb and the DG was compared between groups of parturient ewes which could interact or not with their lamb, and virgins. In addition, a morphological analysis was performed by measuring the dendritic arbor of neuroblasts in both structures. We showed that the postpartum period was associated with a decrease in olfactory and hippocampal adult neurogenesis. In the olfactory bulb, the suppressive effect on neuroblasts was dependent on interactions with the young whereas in the DG the decrease in new mature neurons was associated with parturition. In addition, dendritic length and number of nodes of neuroblasts were significantly enhanced by interactions with the lamb in the olfactory bulb but not in the DG. Because interactions with the young involved learning of the olfactory signature of the lamb, we hypothesize that this learning is associated with a down-regulation in olfactory neurogenesis and an enhancement of olfactory neuroblast maturation. Our assumption is that fewer new neurons decrease cell competition in the olfactory bulb and enhance maturation of those new neurons selected to participate in the learning of the young odor. PMID:24600367

  19. 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

  20. Energy distribution of the particles obtained after irradiation of carbon nanotubes with carbon projectiles

    International Nuclear Information System (INIS)

    The idea of using carbon nanotubes (CNTs) as masks against irradiation has recently emerged, because of the region of a given material covered by a CNT can be protected from the effects of irradiation, creating nanowires. In this case, it is interesting to know in detail the number of generated recoils and their energy. In order to obtain these data, we simulate the irradiation of CNTs with carbon ions using a molecular dynamics code. To describe the interaction between carbon ions we use the Brenner potential joined smoothly to the Universal ZBL potential at short distances. We have analyzed the energy distributions of the carbon atoms emerging from the CNT for single projectile irradiation with incident energies from 30 eV to 5 keV. Our results show that the number and the energy of the recoil carbon atoms emerging from the CNT increases with the projectile incident energy. In average, each projectile with incident energy of 1 keV produces ∼3.6 recoils, which have a mean energy of 150 eV, while projectiles with 5 keV produce ∼7 recoils with a mean energy of 400 eV

  1. 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

  2. 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.

  3. 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

  4. 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.

  5. Exposure to nanoscale particles and fibers during machining of hybrid advanced composites containing carbon nanotubes

    International Nuclear Information System (INIS)

    This study investigated airborne exposures to nanoscale particles and fibers generated during dry and wet abrasive machining of two three-phase advanced composite systems containing carbon nanotubes (CNTs), micron-diameter continuous fibers (carbon or alumina), and thermoset polymer matrices. Exposures were evaluated with a suite of complementary instruments, including real-time particle number concentration and size distribution (0.005-20 μm), electron microscopy, and integrated sampling for fibers and respirable particulate at the source and breathing zone of the operator. Wet cutting, the usual procedure for such composites, did not produce exposures significantly different than background whereas dry cutting, without any emissions controls, provided a worst-case exposure and this article focuses here. Overall particle release levels, peaks in the size distribution of the particles, and surface area of released particles (including size distribution) were not significantly different for composites with and without CNTs. The majority of released particle surface area originated from the respirable (1-10 μm) fraction, whereas the nano fraction contributed ∼10% of the surface area. CNTs, either individual or in bundles, were not observed in extensive electron microscopy of collected samples. The mean number concentration of peaks for dry cutting was composite dependent and varied over an order of magnitude with highest values for thicker laminates at the source being >1 x 106 particles cm-3. Concentration of respirable fibers for dry cutting at the source ranged from 2 to 4 fibers cm-3 depending on the composite type. Further investigation is required and underway to determine the effects of various exposure determinants, such as specimen and tool geometry, on particle release and effectiveness of controls.

  6. Effect of carbon nanofibers on tensile and compressive characteristics of hollow particle filled composites

    International Nuclear Information System (INIS)

    The effect of presence of carbon nanofibers on the tensile and compressive properties of hollow particle filled composites is studied. Such composites, called syntactic foams, are known to have high specific modulus and low moisture absorption capabilities and are finding applications as core materials in aerospace and marine sandwich structures. The results of this study show that addition of 0.25 wt.% carbon nanofibers results in improvement in tensile modulus and strength compared to similar syntactic foam compositions that did not contain nanofibers. Compressive modulus decreased and strength remained largely unchanged for most compositions. Tensile and compressive failure features are analyzed using scanning electron microscopy.

  7. An infrared spectroscopic study of the adsorption of carbon monoxide on silica-supported copper particles

    OpenAIRE

    De Jong, K P; Geus, John W.; Joziasse, J.

    2006-01-01

    Infrared spectroscopy is used to study the adsorption of carbon monoxide (20°C; 0.1– 100 Torr) on copper-on-silica catalysts differently prepared and pretreated. As determined by electron microscopy and X-ray line broadening, the catalysts contain copper particles having sizes of 60 to 5000 Å depending on the preparation procedure and the thermal treatment. Adsorbed carbon monoxide displays broad infrared absorption bands exhibiting a maximum at 2099 to 2146 cm-1. The position of the maximum ...

  8. 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.

  9. Application of carbon fiber composite materials for the collision sections of particle accelerators

    International Nuclear Information System (INIS)

    Components made of carbon fiber composite material (CFCM) with Epoxy or BMI matrix were designed for various applications such as vacuum tubes, vertex chambers or support structures. The outstanding properties of CFCM which in many aspects are superior to metal structures especially qualify CFCM components for use in the collision sections of particle accelerators. A total of some 50 m of CFCM beam-tubes and of around 20 different CFCM structures and support elements of various configurations were produced following the specific needs and requirements of high energy particle physics at CERN, DESY and several other research institutes

  10. 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.

  11. 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

  12. 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.

  13. 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.

  14. 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

  15. 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.

  16. 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

  17. 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

  18. 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.

  19. 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

  20. 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.

  1. 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

  2. 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.)

  3. Single-particle and collective dynamics of methanol confined in carbon nanotubes: a computer simulation study

    International Nuclear Information System (INIS)

    We present the results of computer simulations of methanol confined in carbon nanotubes. Different levels of confinement were identified as a function of the nanotube radius and characterized using a pair-distribution function adapted to the cylindrical geometry of these systems. Dynamical properties of methanol were also analysed as a function of the nanotube size, both at the level of single-particle and collective properties. We found that confinement in narrow carbon nanotubes strongly affects the dynamical properties of methanol with respect to the bulk phase, due to the strong interaction with the carbon nanotube. In the other cases, confined methanol shows properties quite similar to those of the bulk phase. These phenomena are related to the peculiar hydrogen bonded network of methanol and are compared to the behaviour of water confined in similar conditions. The effect of nanotube flexibility on the dynamical properties of confined methanol is also discussed.

  4. 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.

  5. 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

  6. 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 .

  7. 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.

  8. 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.

  9. 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

  10. Biocompatible Label-Free Detection of Carbon Black Particles by Femtosecond Pulsed Laser Microscopy.

    Science.gov (United States)

    Bové, Hannelore; Steuwe, Christian; Fron, Eduard; Slenders, Eli; D'Haen, Jan; Fujita, Yasuhiko; Uji-I, Hiroshi; vandeVen, Martin; Roeffaers, Maarten; Ameloot, Marcel

    2016-05-11

    Although adverse health effects of carbon black (CB) exposure are generally accepted, a direct, label-free approach for detecting CB particles in fluids and at the cellular level is still lacking. Here, we report nonincandescence related white-light (WL) generation by dry and suspended carbon black particles under illumination with femtosecond (fs) pulsed near-infrared light as a powerful tool for the detection of these carbonaceous materials. This observation is done for four different CB species with diameters ranging from 13 to 500 nm, suggesting this WL emission under fs near-infrared illumination is a general property of CB particles. As the emitted radiation spreads over the whole visible spectrum, detection is straightforward and flexible. The unique property of the described WL emission allows optical detection and unequivocal localization of CB particles in fluids and in cellular environments while simultaneously colocalizing different cellular components using various specific fluorophores as shown here using human lung fibroblasts. The experiments are performed on a typical multiphoton laser-scanning microscopy platform, widely available in research laboratories. PMID:27104759

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. Carbon content and C:N ratio of transparent exopolymeric particles (TEP) produced by bubbling exudates of diatoms

    OpenAIRE

    Mari, Xavier

    1999-01-01

    The carbon content of transparent exopolymeric particles (TEP) was measured in the laboratory in particles produced by bubbling exudates of the diatom Thalassiosira weissflogii, grown under nitrogen non-limited conditions (N:P = 7). The carbon content of these particles (TEP-C) appears to vary as a function of their size according to TEP-C = 0.25 x 10-6 r2.55 (µg C TEP-1), where r is the equivalent spherical radius of the TEP particle (µm). This relationship implies that TEP are fractal aggre...

  16. 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...

  17. 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...

  18. 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...

  19. 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...

  20. 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...

  1. 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...

  2. 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...

  3. Mechanism of the down-regulation of cAMP receptor protein by glucose in Escherichia coli: role of autoregulation of the crp gene.

    OpenAIRE

    ISHIZUKA, H; Hanamura, A; Inada, T; Aiba, H.

    1994-01-01

    Glucose causes catabolite repression by lowering the intracellular levels of both cAMP and cAMP receptor protein (CRP) in Escherichia coli. The molecular mechanism underlying the down-regulation of CRP by glucose has been investigated. We show that glucose lowers the level of crp mRNA without affecting its stability. Replacement of the crp promoter with the bla promoter almost completely abolishes the glucose-mediated regulation of crp expression. Only a slight reduction in the crp expression...

  4. Circulating let-7g is down-regulated in Bernese Mountain dogs with disseminated histiocytic sarcoma and carcinomas - a prospective study

    DEFF Research Database (Denmark)

    Børresen, B; Nielsen, L N; Jessen, L R; Kristensen, A T; Fredholm, M; Cirera Salicio, Susanna

    dogs. Twenty-four different miRNAs were profiled from RNA isolated from whole blood preserved in PAXgene(®) tubes using quantitative real-time PCR (qPCR). The miRNA let-7g was significantly down-regulated in dogs with cancer (P = 0.002) and dogs with DHS (P = 0.011) compared with healthy controls. This...

  5. Quercetin Down-regulates IL-6/STAT-3 Signals to Induce Mitochondrial-mediated Apoptosis in a Non-small-cell Lung-cancer Cell Line, A549

    Directory of Open Access Journals (Sweden)

    Avinaba Mukherjee

    2015-03-01

    Full Text Available Objectives: Quercetin, a flavonoid compound, has been reported to induce apoptosis in cancer cells, but its anti-inflammatory effects, which are also closely linked with apoptosis, if any, on non-small-cell lung cancer (NSCLC have not so far been critically examined. In this study, we tried to determine if quercetin had any demonstrable anti-inflammatory potential, which also could significantly contribute to inducing apoptosis in a NSCLC cell line, A549. Methods: In this context, several assays, including cytotoxicity, flow cytometry and fluorimetry, were done. Gene expression was analyzed by using a western blot analysis. Results: Results revealed that quercetin could induce apoptosis in A549 cells through mitochondrial depolarization by causing an imbalance in B-cell lymphoma 2/Bcl2 Antagonist X (Bcl2/Bax ratio and by down-regulating the interleukine-6/signal transducer and activator of transcription 3 (IL-6/STAT3 signaling pathway. An analysis of the data revealed that quercetin could block nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB activity at early hours, which might cause a down-regulation of the IL-6 titer, and the IL-6 expression, in turn, could inhibit p-STAT3 expression. Down-regulation of both the STAT3 and the NF-κB expressions might, therefore, cause down-regulation of Bcl2 activity because both are major upstream effectors of Bcl2. Alteration in Bcl2 responses might result in an imbalance in the Bcl2/Bax ratio, which could ultimately bring about mitochondria mediated apoptosis in A549 cells. Conclusion: Overall, the finding of this study indicates that a quercetin induced anti-inflammatory pathway in A549 cells appeared to make a significant contribution towards induction of apoptosis in NSCLC and, thus, may have a therapeutic use such as a strong apoptosis inducer in cancer cells.

  6. DMSO Efficiently Down Regulates Pluripotency Genes in Human Embryonic Stem Cells during Definitive Endoderm Derivation and Increases the Proficiency of Hepatic Differentiation

    OpenAIRE

    Czysz, Katherine; Minger, Stephen; Thomas, Nick

    2015-01-01

    Background Definitive endoderm (DE) is one of the three germ layers which during in vivo vertebrate development gives rise to a variety of organs including liver, lungs, thyroid and pancreas; consequently efficient in vitro initiation of stem cell differentiation to DE cells is a prerequisite for successful cellular specification to subsequent DE-derived cell types [1, 2]. In this study we present a novel approach to rapidly and efficiently down regulate pluripotency genes during initiation o...

  7. Resistance to pathogens in terpene down-regulated orange fruits inversely correlates with the accumulation of D-limonene in peel oil glands

    OpenAIRE

    Ana RODRÍGUEZ; Shimada, Takehiko; CERVERA, MAGDALENA; Redondo, Ana; Alquézar, Berta; Rodrigo, María Jesús; Zacarías, Lorenzo; Palou, Lluís; López, María M.; Peña, Leandro

    2015-01-01

    Volatile organic compounds (VOCs) are secondary metabolites acting as a language for the communication of plants with the environment. In orange fruits, the monoterpene D-limonene accumulates at very high levels in oil glands from the peel. Drastic down-regulation of D-limonene synthase gene expression in the peel of transgenic oranges harboring a D-limonene synthase transgene in antisense (AS) configuration altered the monoterpene profile in oil glands, mainly resulting in reduced accumulati...

  8. 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

  9. NMR characterization of altered lignins extracted from tobacco plants down-regulated for lignification enzymes cinnamylalcohol dehydrogenase and cinnamoyl-CoA reductase

    OpenAIRE

    Ralph, John; Hatfield, Ronald D.; Piquemal, Joël; Yahiaoui, Nabila; Pean, Michel; Lapierre, Catherine; Boudet, Alain M.

    1998-01-01

    Homologous antisense constructs were used to down-regulate tobacco cinnamyl-alcohol dehydrogenase (CAD; EC 1.1.1.195) and cinnamoyl-CoA reductase (CCR; EC 1.2.1.44) activities in the lignin monomer biosynthetic pathway. CCR converts activated cinnamic acids (hydroxycinnamoyl–SCoAs) to cinnamaldehydes; cinnamaldehydes are then reduced to cinnamyl alcohols by CAD. The transformations caused the incorporation of nontraditional components into the extractable tobacco lignins, as evidenced by NMR....

  10. Advanced glycation end products-modified proteins and oxidized LDL mediate down-regulation of leptin in mouse adipocytes via CD36

    International Nuclear Information System (INIS)

    Advanced glycation end products (AGE)-modified proteins as well as oxidized-LDL (Ox-LDL) undergo receptor-mediated endocytosis by CHO cells overexpressing CD36, a member of class B scavenger receptor family. The purpose of the present study was to examine the effects of glycolaldehyde-modified BSA (GA-BSA) as an AGE-ligand and Ox-LDL on leptin expression in adipocytes. GA-BSA decreased leptin expression at both protein and mRNA levels in 3T3-L1 adipocytes and mouse epididymal adipocytes. Ox-LDL showed a similar inhibitory effect on leptin expression in 3T3-L1 adipocytes, which effect was protected by N-acetylcysteine, a reactive oxygen species (ROS) inhibitor. Binding of 125I-GA-BSA or 125I-Ox-LDL to 3T3-L1 adipocytes and subsequent endocytic degradation were inhibited by a neutralizing anti-CD36 antibody. Furthermore, this antibody also suppressed Ox-LDL-induced leptin down-regulation. These results clarify that the interaction of GA-BSA and Ox-LDL with CD36 leads to down-regulation of leptin expression via ROS system(s) in 3T3-L1 adipocytes, suggesting that a potential link of AGE- and/or Ox-LDL-induced leptin down-regulation might be linked to insulin-sensitivity in metabolic syndrome

  11. 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.

  12. 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

  13. 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

  14. 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.

  15. 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

  16. Nuclear Factor Erythroid 2-Related Factor 2 Down-Regulation in Oral Neutrophils Is Associated with Periodontal Oxidative Damage and Severe Chronic Periodontitis.

    Science.gov (United States)

    Sima, Corneliu; Aboodi, Guy M; Lakschevitz, Flavia S; Sun, Chunxiang; Goldberg, Michael B; Glogauer, Michael

    2016-06-01

    The balance between reactive oxygen species and antioxidants plays an important role in periodontal health. We previously demonstrated that high reactive oxygen species production by oral polymorphonuclear neutrophils (oPMNs) in chronic periodontitis (CP) refractory to conventional therapy is associated with severe destruction of periodontium. Herein, we show that inhibition of antioxidant production through down-regulation of nuclear factor erythroid 2-related factor 2 (Nrf2) pathway in oPMN, despite enhanced recruitment in the oral cavity, is associated with severe CP. Twenty-four genes in the Nrf2-mediated oxidative stress response pathway were down-regulated in PMNs of diseased patients. Downstream of Nrf2, levels of oPMN superoxide dismutase 1 and catalase were decreased in severe CP, despite increased recruitment. Nrf2(-/-) mice had more severe loss of periodontium in response to periodontitis-inducing subgingival ligatures compared with wild-types. Levels of 8-hydroxy-deoxyguanosine were increased in periodontal lesions of Nrf2(-/-) mice, indicating high oxidative damage. We report, for the first time, Nrf2 pathway down-regulation in oPMNs of patients with severe CP. PMNs of CP patients may be primed for low antioxidant response in the context of high recruitment in the oral cavity, resulting in increased oxidative tissue damage. PMID:27070823

  17. 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

  18. Does carbonation of steel slag particles reduce their toxicity? An in vitro approach.

    Science.gov (United States)

    Ibouraadaten, Saloua; van den Brule, Sybille; Lison, Dominique

    2015-06-01

    Mineral carbonation can stabilize industrial residues and, in the steel industry, may contribute to simultaneously valorize CO2 emissions and slag. We hypothesized that, by restricting the leaching of metals of toxicological concern such as Cr and V, carbonation can suppress the toxicity of these materials. The cytotoxic activity (WST1 assay) of slag dusts collected from a stainless and a Linz-Donawitz (LD) steel plant, before and after carbonation, was examined in J774 macrophages. The release of Cr, V, Fe, Mn and Ni was measured after incubation in artificial lung fluids mimicking the extracellular and phagolysosomal milieu to which particles are confronted after inhalation. LD slag had the higher Fe, Mn and V content, and was more cytotoxic than stainless steel slag. The cytotoxic activity of LD but not of stainless dusts was reduced after carbonation. The cytotoxic activity of the dusts toward J774 macrophages necessitated a direct contact with the cells and was reduced in the presence of inhibitors of phagocytosis (cytochalasin D) or phagolysosome acidification (bafilomycin), pointing to a key role of metallic constituents released in phagolysosomes. This in vitro study supports a limited reduction of the cytotoxic activity of LD, but not of stainless, steel dusts upon carbonation. PMID:25735930

  19. 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

  20. 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.

  1. Physicochemical characteristics and toxic effects of ozone-oxidized black carbon particles

    Science.gov (United States)

    Li, Qian; Shang, Jing; Zhu, Tong

    2013-12-01

    Black carbon (BC) or soot particles formed by combustion are ubiquitous in the atmosphere and have a significant effect on climate and human health. Oxidation can change the physicochemical characteristics of BC, thereby increasing its toxicity. The physicochemical properties of BC and ozone-oxidized BC are investigated in this study through transmission electron microscopy, X-ray photoelectron spectroscopy, diffuse reflectance infrared Fourier transform spectroscopy, ultraviolet-visible spectrophotometry, and electron paramagnetic resonance. The contents of oxygen-containing functional groups, hydrophilicity, water-soluble organic compounds, and free radicals increased after ozone treatment. The redox capacity and cytotoxicity of BC particles were enhanced by ozone oxidation as detected by dithiothreitol (DTT) and 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide assays. The redox activities of different BC particles are compared. Particle phase contributed significantly to total redox activity as detected by the DTT assay. Results indicate that BC particles that have undergone aging in the atmosphere may be more toxic and harmful to human health.

  2. DHA down-regulates phenobarbital-induced cytochrome P450 2B1 gene expression in rat primary hepatocytes by attenuating CAR translocation

    International Nuclear Information System (INIS)

    The constitutive androstane receptor (CAR) plays an important role in regulating the expression of detoxifying enzymes, including cytochrome P450 2B (CYP 2B). Phenobarbital (PB) induction of human CYP 2B6 and mouse CYP 2b10 has been shown to be mediated by CAR. Our previous study showed that PB-induced CYP 2B1 expression in rat primary hepatocytes is down-regulated by both n-6 and n-3 polyunsaturated fatty acids (PUFAs), especially docosahexaenoic acid (DHA); however, the mechanism for this down-regulation by DHA was previously unknown. The objective of the present study was to determine whether change in CAR translocation is involved in the down-regulation by n-6 and n-3 PUFAs of PB-induced CYP 2B1 expression in rat primary hepatocytes. We used 100 μM arachidonic acid, linoleic acid, eicosapentaenoic acid, and DHA to test this hypothesis. PB triggered the translocation of CAR from the cytosol into the nucleus in a dose-dependent and time-dependent manner in our hepatocyte system, and the CAR distribution in rat primary hepatocytes was significantly affected by DHA. DHA treatment decreased PB-inducible accumulation of CAR in the nuclear fraction and increased it in the cytosolic fraction in a dose-dependent manner. The down-regulation of CYP 2B1 expression by DHA occurred in a dose-dependent manner, and a similar pattern was found for the nuclear accumulation of CAR. The results of immunoprecipitation showed a CAR/RXR heterodimer bound to nuclear receptor binding site 1 (NR-1) of the PB-responsive enhancer module (PBREM) of the CYP 2B1gene. The EMSA results showed that PB-induced CAR binding to NR-1 was attenuated by DHA. Taken together, these results suggest that attenuation of CAR translocation and decreased subsequent binding to NR-1 are involved in DHA's down-regulation of PB-induced CYP 2B1 expression

  3. 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

  4. 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

  5. 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)

  6. 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

  7. 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.

  8. 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)

  9. Chemical vapor deposition synthesis of carbon nanospheres over Fe-based glassy alloy particles

    International Nuclear Information System (INIS)

    Highlights: • A mass of carbon nanospheres have been synthesized. • The Fe76Si9B10P5 particles were employed as both the catalyst and support. • Carbon nanospheres with amorphous walls have uniform size distribution (50–150 nm). - Abstract: A mass of carbon nanospheres (CNSs) have been synthesized by chemical vapor deposition of C2H2 directly over Fe-based glassy alloy particles (Fe76Si9B10P5) without the addition of an external catalyst. The morphology and microstructure as well as the growth mechanism of the CNSs have been investigated by using scanning and transmission electron microscopy. The results showed that the obtained products consist of hollow CNSs and CNSs with Fe nanoparticles encapsulated. The CNSs with amorphous walls have high purity (>95%) and uniform size distribution (50–150 nm). The possible formation and growth mechanism of the CNSs were discussed on the basis of the investigation on their initial growth stages

  10. 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

  11. 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%).

  12. 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.

  13. Evidence of Correlation between Catalyst Particles and the Single-Wall Carbon Nanotube Diameter: A First Step towards Chirality Control

    OpenAIRE

    Fiawoo, M.-F. C.; Bonnot, Anne Marie; Amara, H.; Bichara, C.; Thibault-Pénisson, J; Loiseau, A.

    2012-01-01

    Controlling the structure of single-wall carbon nanotubes during their synthesis by chemical vapor deposition remains a challenging issue. Here, using a specific synthesis protocol and ex situ transmission electron microscopy, we perform a statistical analysis of the structure of the tubes and of the catalyst particles from which they grow. We discriminate two nucleation modes, corresponding to different nanotube-particle junctions, that occur independently of the particle size. With the supp...

  14. 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...

  15. 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.

  16. 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.)

  17. Processing and characterization of activated carbon coated magnetic particles for biomedical applications

    Energy Technology Data Exchange (ETDEWEB)

    Ramanujan, R.V. [School of Materials Science and Engineering, Nanyang Technological University, Singapore 639798 (Singapore)]. E-mail: ramanujan@ntu.edu.sg; Purushotham, S. [School of Materials Science and Engineering, Nanyang Technological University, Singapore 639798 (Singapore); Chia, M.H. [School of Materials Science and Engineering, Nanyang Technological University, Singapore 639798 (Singapore)

    2007-05-16

    Synthesis and characterization of Magnetically Targeted Carrier (MTC) powders consisting of activated carbon coated iron particles were carried out. Powders with activated carbon content of 5% by weight (Fe5C) and 35% by weight (Fe35C) were studied. Powders were synthesized via the high energy ball milling route, and the influence of milling time on the morphology, magnetic properties and drug adsorption and desorption characteristics was investigated. Physical and structural characterization included electron microscopy, size analysis, and X-ray diffraction. The magnetic properties, and theophylline adsorption and desorption characteristics were studied. Fe35C milled for 10 h was found to be a suitable candidate for MTC applications with fine size, stable magnetic properties, and superior drug adsorption and desorption behavior.

  18. The measurement of mass and black carbon of fine particles over Klang valley, Kuala Lumpur

    International Nuclear Information System (INIS)

    Fine particles (PM 2.5) of airborne air pollutants samples were collected on weekly basis during the period from 2004-2008 at Klang Valley, Kuala Lumpur. They were analyzed for their mass and black carbon contents. Samples were collected using impactor type air pollutant sampler unit i.e Gent stack sampler capable of collecting of two (2) size groups of air particulate matter, fine (3 and the black carbon was 3.9 - 5.4 μg/m3. The component of BC was about 17% as relative to the gravimetric fine mass. The value for both PM 2.5 and BC were found to be slightly higher during the southwest monsoon May to September due to the haze occasion reported during this season. (Author)

  19. Interaction of Heavy Metal Ions with Carbon and Iron Based Particles

    Directory of Open Access Journals (Sweden)

    Dana Fialova

    2014-03-01

    Full Text Available Due to the rapid development of industry and associated production of toxic waste, especially heavy metals, there is a great interest in creating and upgrading new sorption materials to remove these pollutants from the environment. This study aims to determine the effectiveness of different carbon forms (graphene, expanded carbon, multi-wall nanotubes and paramagnetic particles (Fe2O3 for adsorption of cadmium(II, lead(II, and copper(II on its surface, with different interaction time from 1 min to 24 h. The main attention is paid to the detection of these metals using differential pulse voltammetry. Based on the obtained results, graphene and Fe2O3 are found to be good candidates for removal of heavy metals from the environment.

  20. 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.

  1. 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...

  2. Soot, unburned carbon and ultrafine particle emissions from air- and oxy-coal flames

    International Nuclear Information System (INIS)

    Oxy-coal combustion is one possible solution for the mitigation of greenhouse gases. In this process coal is burned in oxygen, rather than air, and the temperatures in the boiler are mitigated by recycling flue gases, so that the inlet mixture may contain either 27 % O2 to match adiabatic flame temperatures, or 32 % O2 to match gaseous radiation heat fluxes in the combustion chamber. However, a major issue for heat transfer from coal combustion is the radiative heat transmission from soot. For this research, air and oxy coal firing were compared regarding the emission of soot. A 100 kW down-fired laboratory combustor was used to determine effects of switching from air to oxy-firing on soot, unburned carbon and ultrafine particle emissions from practical pulverized coal flames. Of interest here were potential chemical effects of substitution of the N2 in air by CO2 in practical pulverized coal flames. The oxy-coal configuration investigated used once-through CO2, simulating cleaned flue gas recycle with all contaminants and water removed. Three coals were each burned in: a) air, b) 27 % O2/ 73 % CO2, c) 32 % O2/ 68 % CO2. Tests were conducted at (nominally) 3 %, 2 %, 1 % and 0 % O2 in the exhaust (dry basis). For each condition, particulate samples were iso kinetically withdrawn far from the radiant zone, and analyzed using a photoacoustic analyzer (PA) for black carbon, a scanning mobility particle sizer (SMPS) for ultrafine particles, and a total sample loss on ignition (LOI) method for unburned carbon in ash. Data suggest that at low stoichiometric ratios, ultrafine particles consist primarily of black carbon, which, for the bituminous coal, is produced in lesser amounts under oxy-fired conditions than under the air-fired condition, even when adiabatic flame temperatures are matched. However, significant changes in mineral matter vaporization were not observed unless the flames were hotter. These and other results are interpreted in the light of available

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

    OpenAIRE

    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 channels, which are aligned with the intersections of the (100) surface of the wafer and the {110} planes on an oxidized silicon wafer, as well as endotaxial copper silicide nanoparticles within the wafer ...

  4. 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...

  5. 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

  6. 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.

  7. 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.

  8. Levels of black carbon and their relationship with particle number levels-observation at an urban roadside in Taipei City.

    Science.gov (United States)

    Cheng, Yu-Hsiang; Shiu, Ben-Tzung; Lin, Meng-Hsien; Yan, Jhih-Wei

    2013-03-01

    Information on the relationship between black carbon (BC) and particle number levels in urban areas is limited. Therefore, investigating the relationship between BC and particle number levels in different particle size ranges at an urban area is worthwhile. This study used an aethalometer and scanning mobility particle sizer to measure the levels of BC and particle number simultaneously at an urban roadside in Taipei City. Measurement results show that hourly BC levels are 0.62-8.80 μg m(-3) (mean=3.50 μg m(-3)) and hourly particle number levels are 4.21 × 10(3)-4.64 × 10(4) particles cm(-3) (mean=2.00 × 10(4) particles cm(-3)) in Taipei urban area. The BC and particle number levels peak during morning (7:00-9:00) and evening (16:00-18:00) rush hours on weekdays. Low BC and particle number levels exist in the early morning hours. Time variations in BC levels are the same as those of particle number levels in this study, clearly indicating that BC and particles are likely released from the same emission source. Additionally, BC levels in the urban area are more strongly associated with ultrafine particle levels than with total particle number levels, particularly in the size range of 56-180 nm. According to measurement results, most BC in aerosols in urban areas can be in the ultrafine size range. PMID:22798147

  9. 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.

  10. 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.

  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. Real-time and single-particle volatility of elemental carbon-containing particles in the urban area of Pearl River Delta region, China

    Science.gov (United States)

    Bi, Xinhui; Dai, Shouhui; Zhang, Guohua; Qiu, Ning; Li, Mei; Wang, Xinming; Chen, Duohong; Peng, Ping'an; Sheng, Guoying; Fu, Jiamo; Zhou, Zhen

    2015-10-01

    Elemental carbon (EC) aerosol represents an important fraction of aerosol particles in urban area of the Pearl River Delta (PRD) region, China. Previous studies have demonstrated that EC particles in the PRD region undergo significant amounts of aging processes. To assess the degree of aging, the real-time single particle volatility of EC-containing particles was measured in an urban area of the PRD region by a thermodiluter coupled to a single particle aerosol mass spectrometer (SPAMS). The size and chemical composition of the individual particles before and after heating to 75 °C, 150 °C and 300 °C were characterized. Of the total unheated particles examined by SPAMS, 53% of the unheated particles contained EC, and a higher number fraction (69%) was observed in the particles heated to 300 °C. No significant differences in the mass spectral patterns were found between ambient temperature and 75 °C. Nitrate evaporated at 150 °C, and most of sulfate evaporated at 300 °C. EC-containing particles were clustered into four distinct particle types based on the dominant chemical species present in the mass spectra, comprised of EC, internally mixed EC and organic carbon (OC) (ECOC), internally mixed EC and sodium/potassium salt (NaK-EC), and internally mixed EC and metal species (Metal-EC). Detail analysis show that the volatility of EC-containing particles relied on the EC particle types. Among the four types, the EC type was quite volatile. A significant fraction of sulfate and organics in the ECOC type did not volatilize at 300 °C. The volatilities of secondary ions in the four EC-containing particle types were found to be dependent on their molecular composition. Additionally, the volatility of EC-containing particles decreased during the polluted hazy days due to the generation of low volatile compounds under the atmospheric conditions with higher precursor concentrations and oxidation capacity. To our knowledge, this is the first reported real

  13. Single particle characterization of black carbon aerosols at a tropospheric alpine site in Switzerland

    Directory of Open Access Journals (Sweden)

    D. Liu

    2010-08-01

    Full Text Available The refractory black carbon (rBC mass, size distribution (190–720 nm and mixing state in sub-micron aerosols were characterized from late February to March 2007 using a single particle incandescence method at the high alpine research station Jungfraujoch (JFJ, Switzerland (46.33° N, 7.59° E, 3580 m a.s.l.. JFJ is a ground based location, which is at times exposed to continental free tropospheric air. A median mass absorption coefficient (MAC of 10.2±3.2 m2 g−1 at λ=630 nm was derived by comparing single particle incandescence measurements of black carbon mass with continuous measurements of absorption coefficient. This value is comparable with other estimates at this location. The aerosols measured at the site were mostly well mixed and aged during transportation via the free troposphere. Pollutant sources were traced by air mass back trajectories, trace gases concentrations and the mass loading of rBC. In southeasterly wind directions, mixed or convective weather types provided the potential to vent polluted boundary layer air from the southern Alpine area and industrial northern Italy, delivering enhanced rBC mass loading and CN concentrations to the JFJ. The aerosol loadings at this site were also significantly influenced by precipitation, which led to the removal of rBC from the atmosphere. Precipitation events were shown to remove about 65% of the rBC mass from the free tropospheric background reducing the mean loading from 13±5 ng m−3 to 6±2 ng m−3(corrected to standard temperature and pressure. Overall, 40±15% of the observed rBC particles within the detectable size range were mixed with large amounts of non-refractory materials present as a thick coating. The growth of particle size into the accumulation mode was positively linked with the degree of rBC mixing, suggesting the important role of condensable materials in increasing particle size and leading to enhanced internal

  14. 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

  15. 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

  16. IL-28B down-regulates regulatory T cells but does not improve the protective immunity following tuberculosis subunit vaccine immunization.

    Science.gov (United States)

    Luo, Yanping; Ma, Xingming; Liu, Xun; Lu, Xiaoling; Niu, Hongxia; Yu, Hongjuan; Bai, Chunxiang; Peng, Jinxiu; Xian, Qiaoyang; Wang, Yong; Zhu, Bingdong

    2016-02-01

    Regulatory T cells (Tregs), which could be down-regulated by IL-28B, were reported to suppress T-cell-mediated immunity. The aim of this study was to investigate the role of IL-28B on the immune responses and protective efficacy of a tuberculosis (TB) subunit vaccine. First, a recombinant adenoviral vector expressing mouse IL-28B (rAd-mIL-28B) was constructed; then C57BL/6 mice were immunized with subunit vaccine ESAT6-Ag85B-Mpt64(190-198)-Mtb8.4-HspX (EAMMH) and rAd-mIL-28B together thrice or primed with Mycobacterium bovis bacillus Calmette-Gue'rin (BCG) and boosted by EAMMH and rAd-mIL-28B twice. At last the immune responses were evaluated, and the mice primed with BCG and boosted by subunit vaccines were challenged with virulent Mycobacterium tuberculosis H37Rv to evaluate the protective efficacy. The results showed that rAd-mIL-28B treatment significantly down-regulated the frequency of Tregs at 4 weeks after the last immunization but did not increase the Th1-type immune responses. Moreover, in the regimen of BCG priming and EAMMH boosting, rAd-mIL-28B treatment did not increase the antigen-specific cellular and humoral immune responses, and consequently did not reduce the bacteria load following H37Rv challenge. Instead, it induced more serious pathology reaction. In conclusion, IL-28B down-regulates Tregs following EAMMH vaccination but does not improve the protective immune responses. PMID:26521300

  17. Nicotine-induced retardation of chondrogenesis through down-regulation of IGF-1 signaling pathway to inhibit matrix synthesis of growth plate chondrocytes in fetal rats

    International Nuclear Information System (INIS)

    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

  18. 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

  19. 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.

  20. Consequences of antisense down-regulation of a lignification-specific peroxidase on leaf and vascular tissue in tobacco lines demonstrating enhanced enzymic saccharification.

    Science.gov (United States)

    Kavousi, Bahram; Daudi, Arsalan; Cook, Charis M; Joseleau, Jean-Paul; Ruel, Katia; Devoto, Alessandra; Bolwell, G Paul; Blee, Kristopher A

    2010-04-01

    Tobacco plants expressing an antisense construct for a cationic peroxidase, which down-regulated lignin content at the presumed level of polymerisation, have been further analysed. T(1) plants were derived from a large-scale screen of T(0) mutant lines, previously published, which identified lines demonstrating consistent lignin down-regulation. Of these, line 1074 which had the most robust changes in lignin distribution through several generations was shown to have accompanying down-regulation of transcription of most lignin biosynthesis genes, except cinnamoyl-CoA reductase. The consistent 20% reduction in lignin was not accompanied by significant gross changes in vascular polysaccharide content and composition, despite a modest up-regulation of transcripts of genes involved in cellulose and hemicellulose synthesis. Morphologically, 1074 plants have under-developed xylem with both fibers and vessels having thin cell walls and limited secondary wall thickening with an abnormal S2 layer. However, they were not compromised in overall growth. Nevertheless, these and other lines showed improved potential industrial utility through a threefold increase in enzymic saccharification efficiency compared with wild-type (wt). Therefore, they were profiled for further un-intended effects of transgenesis that might compromise their value for industrial or biofuel processes. Other phenotypic changes included increased leaf thickness and bifurcation at the tip of the leaf. wt-Plants had smaller chloroplasts and higher stomatal numbers than mutants. Transgenic lines also showed a variable leaf pigment distribution with light-green areas that contained measurably less chlorophyll a, b, and carotenoids. Changes in epidermal pavement cells of mutant lines were also observed after exposure to various chemicals, while wt leaves retained their structural integrity. Despite these changes, the mutant plants grew and were viable indicating that lignification patterns can be manipulated

  1. Ambient black carbon particle hygroscopic properties controlled by mixing state and composition

    Directory of Open Access Journals (Sweden)

    D. Liu

    2013-02-01

    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

  2. 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

  3. 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

  4. 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 ...

  5. Chronic Ultraviolet B Irradiation Causes Loss of Hyaluronic Acid from Mouse Dermis Because of Down-Regulation of Hyaluronic Acid Synthases

    OpenAIRE

    Dai, Guang; Freudenberger, Till; Zipper, Petra; Melchior, Ariane; Grether-Beck, Susanne; Rabausch, Berit; de Groot, Jens; Twarock, Sören; Hanenberg, Helmut; Homey, Bernhard; Krutmann, Jean; Reifenberger, Julia; Fischer, Jens W.

    2007-01-01

    Remodeling of the dermal extracellular matrix occurs during photoaging. Here, the effect of repetitive UVB irradiation on dermal hyaluronic acid (HA) was examined. C57/BL6 mice were chronically (182 days) irradiated with UVB, and consecutive skin biopsies were collected during the irradiation period and afterward (300 and 400 days of age). UVB caused marked loss of HA from the papillary dermis and down-regulation of HA synthase 1 (HAS1), HAS2, and HAS3 mRNA expression. In contrast, hyaluronid...

  6. 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...

  7. 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...

  8. 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...

  9. 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 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...

  10. 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.

  11. 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

  12. Proliferation inhibition and apoptosis induction of imatinib-resistant chronic myeloid leukemia cells via PPP2R5C down-regulation

    OpenAIRE

    Shen, Qi; Liu, Sichu; Chen, Yu; Yang, Lijian; CHEN, SHAOHUA; Wu, Xiuli; Li, Bo; Lu, Yuhong; Zhu, Kanger; Li, Yangqiu

    2013-01-01

    Despite the success of imatinib and other tyrosine kinase inhibitors (TKIs), chronic myeloid leukemia (CML) remains largely incurable, and a number of CML patients die due to Abl mutation-related drug resistance and blast crisis. The aim of this study was to evaluate proliferation inhibition and apoptosis induction by down-regulating PPP2R5C gene expression in the imatinib-sensitive and imatinib-resistant CML cell lines K562, K562R (imatinib resistant without an Abl gene mutation), 32D-Bcr-Ab...

  13. Strong iron demand during hypoxia-induced erythropoiesis is associated with down-regulation of iron-related proteins and myoglobin in human skeletal muscle

    DEFF Research Database (Denmark)

    Robach, Paul; Cairo, Gaetano; Gelfi, Cecilia;

    2007-01-01

    , mobilizes body iron, and increases hemoglobin concentration. However, contrary to our hypothesis that muscle iron proteins and myoglobin would also be up-regulated during HA, this study shows that HA lowers myoglobin expression by 35% and down-regulates iron-related proteins in skeletal muscle, as evidenced...... increase. This study gives new insights into the changes in iron content and iron-oxygen interactions during enhanced erythropoiesis by simultaneously analyzing blood and muscle samples in humans exposed to 7 to 9 days of high altitude hypoxia (HA). HA up-regulates iron acquisition by erythroid cells...

  14. 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.

  15. Ion induced transformation of polymer films into diamond-like carbon incorporating silver nano particles

    International Nuclear Information System (INIS)

    Silver containing diamond-like carbon (DLC) is an interesting material for medical engineering from several points of view. On the one hand DLC provides high mechanical robustness. It can be used as biocompatible and wear resistant coating for joint replacing implants. On the other hand silver has antimicrobial properties, which could reduce post-operative inflammations. However conventional production of Ag-DLC by co-deposition of silver and carbon in a plasma process is problematic since it does not allow for a separate control of nano particle morphology and matrix properties. In this work an alternative production method has been developed to circumvent this problem. In metall-DLC-production by ion implantation into a nano composite, silver nano particles are initially formed in solution and then incorporated within a polymer matrix. Finally the polymer is transformed into DLC by ion implantation. The aspects and single steps of this method were investigated with regard to the resulting material's properties. The goal was to design an economically relevant deposition method. Based on experimental results a model of the transformation process has been established, which has also been implemented in a computer simulation. Finally the antibacterial properties of the material have been checked in a biomedical test. Here a bacterial killing rate of 90% could be achieved. (orig.)

  16. 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.

  17. 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

  18. 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.

  19. 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...

  20. 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.

  1. 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.

  2. 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

  3. An enhanced chemiluminescence bioplatform by confining glucose oxidase in hollow calcium carbonate particles.

    Science.gov (United States)

    Wang, Congmin; Zhou, Cuisong; Long, Yuyin; Cai, Honglian; Yin, Cuiyun; Yang, Qiufang; Xiao, Dan

    2016-01-01

    A chemiluminescence (CL) amplification platform based on HCC/Lucigenin&GOx (HLG) film was developed. Hollow structural calcium carbonate (HCC) particles were used as alternative materials for carrying both enzyme and CL reagent. The model enzyme (GOx), immobilized in confined space of HCC particles, exhibited an improved biocatalysis. The Michaelis constant (Km) and the enzymatic rate constant (kcat) were determined to be 0.209 μM and 2.21 s(-1), respectively, which are much better than those of either free GOx in aqueous solution or the GOx immobilized on common nanomaterials. Based on the HLG platform, CL signal was effectively amplified and visualized after adding trace glucose, which could be attributed to the HCC particles' high biocompatibility, large specific surface area, attractive interfacial properties and efficient interaction with analyses. The visual CL bioplatform showed an excellent performance with high selectivity, wide linear range and low detection limit for sensing trace glucose. Because it eliminates the need of complicated assembly procedure and enables visualization by the naked eye, the sensitive and selective CL bioplatform would provide wide potential applications in disease diagnosis and food safety. PMID:27080637

  4. 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

  5. Hypoxia Down-regulates Secretion of MMP-2, MMP-9 in Porcine Pulmonary Artery Endothelial and Smooth Muscle Cells and the Role of HIF-1

    Institute of Scientific and Technical Information of China (English)

    YE Hong; ZHENG Yanfang; MA Wanli; KE Dan; JIN Xianrong; LIU Shengyuan; WANG Dixun

    2005-01-01

    Primary cell culture, techniques of gene transfection, gelatin zymography, and Western blot were used to investigate the effect of hypoxia on the secretion of MMP-2 and MMP-9 in pulmonary artery endothelial cells (PAEC) and smooth muscle cells (PASMC), and the role of HIF-1. Our results showed that (1) after exposure to hypoxia for 24 h, the protein content and activity of MMP-2 in the PAEC medium as well as these of MMP-2 and MMP-9 in PASMC medium (P<0.01) decreased significantly in contrast to those in normoxic group (P<0.05); (2) after transfection of wild type EPO3'-enhancer, a HIF-1 decoy, the content and activity of MMP-2 and MMP-9 in hypoxic mediums became higher than those in normoxic group (P<0.01), while transfection of mutant EPO3'-enhancer didn't affect the hypoxia-induced down-regulation. It is concluded that hypoxia could inhibit the secretion and activity of MMP-2 and MMP-9 in PAEC and PASMC, which could be mitigated by the transfection of EPO3'-enhancer and that HIF-1 pathway might contribute to hypoxia-induced down-regulation of MMP-2 and MMP-9.

  6. 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

  7. 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

  8. 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

  9. Allopregnanolone suppresses diabetes-induced neuropathic pain and motor deficit through inhibition of GABAA receptor down-regulation in the spinal cord of diabetic rats

    Directory of Open Access Journals (Sweden)

    Samira Afrazi

    2014-05-01

    Full Text Available Objective(s:Painful diabetic neuropathy is associated with hyperexcitability and hyperactivity of spinal cord neurons. However, its underlying pathophysiological mechanisms have not been fully clarified. Induction of excitatory/inhibitory neurotransmission imbalance at the spinal cord seems to account for the abnormal neuronal activity in diabetes. Protective properties of neurosteroids have been demonstrated in numerous cellular and animal models of neurodegeneration. Materials and Methods: Here, the protective effects of allopregnanolone, a neurosteroid were investigated in an in vivo model of diabetic neuropathy. The tail-flick test was used to assess the nociceptive threshold. Diabetes was induced by injection of 50 mg/kg (IP streptozotocin. Seven weeks after the induction of diabetes, the dorsal half of the lumbar spinal cord was assayed for the expression of γ2 subunit of GABAA receptor using semiquantitative RT-PCR. Results: The data shows that allopregnanolone (5 and 20 mg/kg markedly ameliorated diabetes-induced thermal hyperalgesia and motor deficit. The weights of diabetic rats that received 5 and 20 mg/kg allopregnanolone did not significantly reduce during the time course of study. Furthermore, this neurosteroid could inhibit GABAA receptor down-regulation induced by diabetes in the rat spinal cord. Conclusion: The data revealed that allopregnanolone has preventive effects against hyperglycemic-induced neuropathic pain and motor deficit which are related to the inhibition of GABAA receptor down-regulation.

  10. 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 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. PMID:27510760

  11. Long Non-Coding RNA HOTAIR Promotes Cell Migration and Invasion via Down-Regulation of RNA Binding Motif Protein 38 in Hepatocellular Carcinoma Cells

    Directory of Open Access Journals (Sweden)

    Chaofeng Ding

    2014-03-01

    Full Text Available Long non-coding RNA HOTAIR exerts regulatory functions in various biological processes in cancer cells, such as proliferation, apoptosis, mobility, and invasion. We previously found that HOX transcript antisense RNA (HOTAIR is a negative prognostic factor and exhibits oncogenic activity in hepatocellular carcinoma (HCC. In this study, we aimed to investigate the role and molecular mechanism of HOTAIR in promoting HCC cell migration and invasion. Firstly, we profiled its gene expression pattern by microarray analysis of HOTAIR loss in Bel-7402 HCC cell line. The results showed that 129 genes were significantly down-regulated, while 167 genes were significantly up-regulated (fold change >2, p < 0.05. Bioinformatics analysis indicated that RNA binding proteins were involved in this biological process. HOTAIR suppression using RNAi strategy with HepG2 and Bel-7402 cells increased the mRNA and protein expression levels of RNA binding motif protein 38 (RBM38. Moreover, the expression levels of RBM38 in HCC specimens were significantly lower than paired adjacent noncancerous tissues. In addition, knockdown of HOTAIR resulted in a decrease of cell migration and invasion, which could be specifically rescued by down-regulation of RBM38. Taken together, HOTAIR could promote migration and invasion of HCC cells by inhibiting RBM38, which indicated critical roles of HOTAIR and RBM38 in HCC progression.

  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. 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

  14. 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

  15. 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

  16. MicroRNA-21 induces resistance to 5-fluorouracil by down-regulating human DNA MutS homolog 2 (hMSH2).

    Science.gov (United States)

    Valeri, Nicola; Gasparini, Pierluigi; Braconi, Chiara; Paone, Alessio; Lovat, Francesca; Fabbri, Muller; Sumani, Khlea M; Alder, Hansjuerg; Amadori, Dino; Patel, Tushar; Nuovo, Gerard J; Fishel, Richard; Croce, Carlo M

    2010-12-01

    The overexpression of microRNA-21 (miR-21) is linked to a number of human tumors including colorectal cancer, where it appears to regulate the expression of tumor suppressor genes including p21, phosphatase and tensin homolog, TGFβ receptor II, and B-cell leukemia/lymphoma 2 -associated X protein. Here we demonstrate that miR-21 targets and down-regulates the core mismatch repair (MMR) recognition protein complex, human mutS homolog 2 (hMSH2) and 6 (hMSH6). Colorectal tumors that express a high level of miR-21 display reduced hMSH2 protein expression. Cells that overproduce miR-21 exhibit significantly reduced 5-fluorouracil (5-FU)-induced G2/M damage arrest and apoptosis that is characteristic of defects in the core MMR component. Moreover, xenograft studies demonstrate that miR-21 overexpression dramatically reduces the therapeutic efficacy of 5-FU. These studies suggest that the down-regulation of the MMR mutator gene associated with miR-21 overexpression may be an important clinical indicator of therapeutic efficacy in colorectal cancer. PMID:21078976

  17. Combined down-regulation by aromatase inhibitor and GnRH-agonist in IVF patients with endometriomas-A pilot study

    DEFF Research Database (Denmark)

    Lossl, Kristine; Løssl, Kristine; Loft, Anne; Freiesleben, Nina L C; Bangsbøll, Susanne; Andersen, Claus Yding; Pedersen, Anette T; Hartwell, Dorthe; Andersen, Anders Nyboe

    2009-01-01

    . The aim of this study was to test the concept of combined down-regulation prior to IVF in patients with endometriomas. STUDY DESIGN: Prospective pilot study in a university-based tertiary fertility clinic including 20 infertile patients with endometriomas undergoing IVF/ICSI. The patients received...... goserelin 3.6mg sc on treatment Days 1, 28 and 56, and one daily tablet of anastrozole 1mg from Day 1 to Day 69. Controlled ovarian stimulation was initiated from Day 70. Outcome measures were change in endometriomal volume and serum CA125 during down-regulation, standard IVF parameters including pregnancy......), P=0.007 and P=0.001). In the IVF/ICSI cycle, the number of oocytes retrieved was 7.5 (6.0-10.0) and the fertilization rate was 0.78 (0.38-1.0). Nine patients (45%) conceived, five (25%) had a clinical pregnancy, and three (15%) delivered healthy children (two singletons and one twin). CONCLUSIONS...

  18. Systems analysis reveals down-regulation of a network of pro-survival miRNAs drives the apoptotic response in dilated cardiomyopathy

    Science.gov (United States)

    Isserlin, Ruth; Merico, Daniele; Wang, Dingyan; Vuckovic, Dajana; Bousette, Nicolas; Gramolini, Anthony O.; Bader, Gary D.; Emili, Andrew

    2016-01-01

    Apoptosis is a hallmark of multiple etiologies of heart failure, including dilated cardiomyopathy. Since microRNAs are master regulators of cardiac development and key effectors of intracellular signaling, they represent novel candidates for understanding the mechanisms driving the increased dysfunction and loss of cardiomyocytes during cardiovascular disease progression. To determine the role of cardiac miRNAs in the apoptotic response, we used microarray technology to monitor miRNA levels in a validated murine phospholambam mutant model of dilated cardiomyopathy. 24 miRNAs were found to be differentially expressed, most of which have not been previously linked to dilated cardiomyopathy. We showed that individual silencing of 7 out of 8 significantly down-regulated miRNAs (mir-1, −29c, −30c, −30d, −149, −486, −499) led to a strong apoptotic phenotype in cell culture, suggesting they repress pro-apoptotic factors. To identify putative miRNA targets most likely relevant to cell death, we computationally integrated transcriptomic, proteomic and functional annotation data. We showed the dependency of prioritized target abundance on miRNA expression using RNA interference and quantitative mass spectrometry. We concluded that down regulation of key pro-survival miRNAs causes up-regulation of apoptotic signaling effectors that contribute to cardiac cell loss, potentially leading to system decompensation and heart failure. PMID:25361207

  19. 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 sec