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Sample records for activator pla activity

  1. An Active Site Water Network in the Plasminogen Activator Pla from Yersinia pestis

    SciTech Connect

    Eren, Elif; Murphy, Megan; Goguen, Jon; van den Berg, Bert

    2010-08-13

    The plasminogen activator Pla from Yersinia pestis is an outer membrane protease (omptin) that is important for the virulence of plague. Here, we present the high-resolution crystal structure of wild-type, enzymatically active Pla at 1.9 {angstrom}. The structure shows a water molecule located between active site residues D84 and H208, which likely corresponds to the nucleophilic water. A number of other water molecules are present in the active site, linking residues important for enzymatic activity. The R211 sidechain in loop L4 is close to the nucleophilic water and possibly involved in the stabilization of the oxyanion intermediate. Subtle conformational changes of H208 result from the binding of lipopolysaccharide to the outside of the barrel, explaining the unusual dependence of omptins on lipopolysaccharide for activity. The Pla structure suggests a model for the interaction with plasminogen substrate and provides a more detailed understanding of the catalytic mechanism of omptin proteases.

  2. Zinc Metalloproteinase ProA Directly Activates Legionella pneumophila PlaC Glycerophospholipid:cholesterol Acyltransferase*

    PubMed Central

    Lang, Christina; Rastew, Elena; Hermes, Björn; Siegbrecht, Enrico; Ahrends, Robert; Banerji, Sangeeta; Flieger, Antje

    2012-01-01

    Enzymes secreted by Legionella pneumophila, such as phospholipases A (PLAs) and glycerophospholipid:cholesterol acyltransferases (GCATs), may target host cell lipids and therefore contribute to the establishment of Legionnaires disease. L. pneumophila possesses three proteins, PlaA, PlaC, and PlaD, belonging to the GDSL family of lipases/acyltransferases. We have shown previously that PlaC is the major GCAT secreted by L. pneumophila and that the zinc metalloproteinase ProA is essential for GCAT activity. Here we characterized the mode of PlaC GCAT activation and determined that ProA directly processes PlaC. We further found that not only cholesterol but also ergosterol present in protozoa was palmitoylated by PlaC. Such ester formations were not induced by either PlaA or PlaD. PlaD was shown here to possess lysophospholipase A activity, and interestingly, all three GDSL enzymes transferred short chain fatty acids to sterols. The three single putative catalytic amino acids (Ser-37, Asp-398, and His-401) proved essential for all PlaC-associated PLA, lysophospholipase A, and GCAT activities. A further four cysteine residues are important for the PLA/GCAT activities as well as their oxidized state, and we therefore conclude that PlaC likely forms at least one disulfide loop. Analysis of cleavage site and loop deletion mutants suggested that for GCAT activation deletion of several amino acids within the loop is necessary rather than cleavage at a single site. Our data therefore suggest a novel enzyme inhibition/activation mechanism where a disulfide loop inhibits PlaC GCAT activity until the protein is exported to the external space where it is ProA-activated. PMID:22582391

  3. Preparation and characterization of biodegradable active PLA film for food packaging

    NASA Astrophysics Data System (ADS)

    Di Maio, L.; Scarfato, P.; Avallone, E.; Galdi, M. R.; Incarnato, L.

    2014-05-01

    In this work we report on the preparation and characterization of a biodegradable active PLA film (aPLA), intended for food packaging applications. The film was obtained by cast extrusion blending a commercial PLA matrix with an active system, developed in our laboratory and based on PLA microparticles containing a-tocopherol (aTCP) as natural antioxidant agent. In order to optimize the film composition and processing, the active microparticles were preliminarily characterized with the aim to evaluate their morphology (size and shape), thermal resistance and a-tocopherol content. The aPLA film, produced with a 5wt% of aTCP, was characterized in terms of performance and activity. The experimental results demonstrated that the aPLA film has mechanical, thermal, barrier and optical properties adequate for packaging applications and shows oxygen scavenging activity and prolonged exhaustion lag time, compared to pure PLA films.

  4. Adhesive properties of the purified plasminogen activator Pla of Yersinia pestis.

    PubMed

    Lobo, Leandro Araujo

    2006-09-01

    The beta-barrel outer membrane protease Pla from Yersinia pestis is an important virulence factor in plague and enables initiation of the bubonic plague. Pla is a multifunctional protease whose expression also enhances bacterial adherence to extracellular matrix. It has remained uncertain whether the increase in cellular adhesiveness results from modification of the bacterial surface by Pla, or whether the Pla molecule is an adhesin. Pla was purified as a His6-fusion protein from Escherichia coli and reconstituted with lipopolysaccharide to an enzymatically active form. Purified His6-Pla was coated onto fluorescent micro-particles (FMPs) that expressed plasminogen activity. Pla-coated FMPs also bound to laminin and to reconstituted basement membrane (Matrigel) immobilized on permanox slides, whereas only poor activity was seen with lipopolysaccharide-coated FMPs or bovine serum albumin-coated FMPs. The results show that the Pla molecule has intrinsic adhesive properties and that purified transmembrane proteins coated onto FMPs can be used for functional assays. PMID:16923070

  5. Improved antifungal activity of itraconazole-loaded PEG/PLA nanoparticles.

    PubMed

    Essa, Sherief; Louhichi, Fatiha; Raymond, Martine; Hildgen, Patrice

    2013-01-01

    Poly(ethylene glycol)/polylactic acid (PEG/PLA) nanoparticles (NPs) containing the hydrophobic antifungal itraconazole (ITZ) were developed to provide a controlled release pattern of ITZ as well as to improve its aqueous dispersibility and hence enhance its antifungal action. Two PEG/PLA copolymers (PEGylated PLA polymers) were used in this study; branched PEGylated polymer in which PEG was grafted on PLA backbone at 7% (mol/mol of lactic acid monomer), PEG7%-g-PLA, and multiblock copolymer of PLA and PEG, (PLA-PEG-PLA)n with nearly similar PEG insertion ratio and similar PEG chain length. ITZ-loaded PLA NPs were also prepared and included in this study as a control. ITZ-NPs were prepared from a 1 : 1 w/w blend of PLA and each PEGylated polymer either PEG7%-g-PLA or (PLA-PEG-PLA)n using an oil-in-water emulsion evaporation method. The NPs morphology, size and size distribution, zeta potential, loading efficiency, release profile and antifungal activity were characterized. All ITZ-NPs were nearly spherical with smooth surface and showed less aggregating tendency with a size range of 185-285 nm. All ITZ-NPs measured nearly neutral zeta potential values close to 0 mV. The % LE of ITZ was ∼94% for PEG7%-g-PLA NPs and ∼83% for (PLA-PEG-PLA)n at 15.3% w/w theoretical loading. PEG/PLA NPs were stable over time regarding size and size distribution and % ITZ loading efficiency (% LE). ITZ release showed an initial burst followed by a gradual release profile for ITZ-NPs over 5 days. (PLA-PEG-PLA)n NPs exhibited faster release rates than PEG7%-g-PLA NPs particularly at the last 2 days. Differential scanning calorimetry and powder X-ray diffractometry data confirmed that ITZ exists in an amorphous state or a solid solution state into the NPs matrix. Fourier transform infrared revealed the possibility of chemical interaction between ITZ and the NPs matrix polymer indicating the successful entrapment of ITZ inside the particles. In haemolysis test, ITZ-NPs caused

  6. Cytosolic PLA2(alpha) activation in Purkinje neurons and its role in AMPA-receptor trafficking.

    PubMed

    Mashimo, Masato; Hirabayashi, Tetsuya; Murayama, Toshihiko; Shimizu, Takao

    2008-09-15

    Cytosolic phospholipase A(2)alpha (cPLA(2)alpha) selectively releases arachidonic acid from membrane phospholipids and has been proposed to be involved in the induction of long-term depression (LTD), a form of synaptic plasticity in the cerebellum. This enzyme requires two events for its full activation: Ca(2+)-dependent translocation from the cytosol to organelle membranes in order to access phospholipids as substrates, and phosphorylation by several kinases. However, the subcellular distribution and activation of cPLA(2)alpha in Purkinje cells and the role of arachidonic acid in cerebellar LTD have not been fully elucidated. In cultured Purkinje cells, stimulation of AMPA receptors, but not metabotropic glutamate receptors, triggered translocation of cPLA(2)alpha to the somatic and dendritic Golgi compartments. This translocation required Ca(2+) influx through P-type Ca(2+) channels. AMPA plus PMA, a chemical method for inducing LTD, released arachidonic acid via phosphorylation of cPLA(2)alpha. AMPA plus PMA induced a decrease in surface GluR2 for more than 2 hours. Interestingly, this reduction was occluded by a cPLA(2)alpha-specific inhibitor. Furthermore, PMA plus arachidonic acid caused the prolonged internalization of GluR2 without activating AMPA receptors. These results suggest that cPLA(2)alpha regulates the persistent decrease in the expression of AMPA receptors, underscoring the role of cPLA(2)alpha in cerebellar LTD. PMID:18713832

  7. Inhibition mechanism of P-glycoprotein mediated efflux by mPEG-PLA and influence of PLA chain length on P-glycoprotein inhibition activity.

    PubMed

    Li, Wenjing; Li, Xinru; Gao, Yajie; Zhou, Yanxia; Ma, Shujin; Zhao, Yong; Li, Jinwen; Liu, Yan; Wang, Xinglin; Yin, Dongdong

    2014-01-01

    The present study aimed to investigate the effect of monomethoxy poly(ethylene glycol)-block-poly(D,L-lactic acid) (mPEG-PLA) on the activity of P-glycoprotein (P-gp) in Caco-2 cells and further unravel the relationship between PLA chain length in mPEG-PLA and influence on P-gp efflux and the action mechanism. The transport results of rhodamine 123 (R123) across Caco-2 cell monolayers suggested that mPEG-PLA unimers were responsible for its P-gp inhibitory effect. Furthermore, transport studies of R123 revealed that the inhibitory potential of P-gp efflux by mPEG-PLA analogues was strongly correlated with their structural features and showed that the hydrophilic mPEG-PLA copolymers with an intermediate PLA chain length and 10.20 of hydrophilic-lipophilic balance were more effective at inhibiting P-gp efflux in Caco-2 cells. The fluorescence polarization measurement results ruled out the plasma membrane fluidization as a contributor for inhibition of P-gp by mPEG-PLA. Concurrently, mPEG-PLA inhibited neither basal P-gp ATPase (ATP is adenosine triphosphate) activity nor substrate stimulated P-gp ATPase activity, suggesting that mPEG-PLA seemed not to be a substrate of P-gp and a competitive inhibitor. No evident alteration in P-gp surface level was detected by flow cytometry upon exposure of the cells to mPEG-PLA. The depletion of intracellular ATP, which was likely to be a result of partial inhibition of cellular metabolism, was directly correlated with inhibitory potential for P-gp mediated efflux by mPEG-PLA analogues. Hence, intracellular ATP-depletion appeared to be possible explanation to the inhibition mechanism of P-gp by mPEG-PLA. Taken together, the establishment of a relationship between PLA chain length and impact on P-gp efflux activity and interpretation of action mechanism of mPEG-PLA on P-gp are of fundamental importance and will facilitate future development of mPEG-PLA in the drug delivery area.

  8. The Rickettsia prowazekii ExoU Homologue Possesses Phospholipase A1 (PLA1), PLA2, and Lyso-PLA2 Activities and Can Function in the Absence of Any Eukaryotic Cofactors In Vitro ▿

    PubMed Central

    Housley, Nicole A.; Winkler, Herbert H.; Audia, Jonathon P.

    2011-01-01

    Here we have characterized the Rickettsia prowazekii RP534 protein, a homologue of the Pseudomonas aeruginosa ExoU phospholipase A (PLA) secreted cytotoxin. Our studies showed that purified recombinant RP534 PLA possessed the predicted PLA2 and lyso-PLA2 activities based on what has been published for P. aeruginosa ExoU. RP534 also displayed PLA1 activity under the conditions tested, whereas ExoU did not. In addition, recombinant RP534 displayed a basal PLA activity that could hydrolyze phosphatidylcholine in the absence of any eukaryotic cofactors. Interestingly, the addition of bovine liver superoxide dismutase 1 (SOD1), a known activator of P. aeruginosa ExoU, resulted in an increased rate of RP534-catalyzed phospholipid hydrolysis, indicating that mechanisms of activation of the ExoU family of PLAs may be evolutionarily conserved. The mechanism of SOD1-dependent stimulation of RP534 was further examined using active site mutants and a fluorogenic phospholipid substrate whose hydrolysis by RP534 over a short time course is measureable only in the presence of SOD1. These studies suggest a mechanism by which SOD1 stimulates RP534 activity once it has bound to the substrate. We also show that antibody raised against RP534 was useful for immunoprecipitating active RP534 from R. prowazekii lysed cell extracts, thus verifying that this protein is expressed and active in rickettsiae isolated from embryonated hen egg yolk sacs. PMID:21764940

  9. Participation of PLA2 and PLC in DhL-induced activation of Rhinella arenarum oocytes.

    PubMed

    Zapata-Martínez, J; Medina, M F; Gramajo-Bühler, M C; Sánchez-Toranzo, G

    2016-08-01

    Rhinella arenarum oocytes can be artificially activated, a process known as parthenogenesis, by a sesquiterpenic lactone of the guaianolide group, dehydroleucodine (DhL). Transient increases in the concentration of cytosolic Ca2+ are essential to trigger egg activation events. In this sense, the 1-4-5 inositol triphosphate receptors (IP3R) seem to be involved in the Ca2+ transient release induced by DhL in this species. We analyzed the involvement of phosphoinositide metabolism, especially the participation of phospholipase A2 (PLA2) and phospholipase C (PLC) in DhL-induced activation. Different doses of quinacrine, aristolochic acid (ATA) (PLA2 inhibitors) or neomycin, an antibiotic that binds to PIP2, thus preventing its hydrolysis, were used in mature Rhinella arenarum oocytes. In order to assay the participation of PI-PLC and PC- PLC we used U73122, a competitive inhibitor of PI-PLC dependent events and D609, an inhibitor of PC-PLC. We found that PLA2 inhibits quinacrine more effectively than ATA. This difference could be explained by the fact that quinacrine is not a specific inhibitor for PLA2 while ATA is specific for this enzyme. With respect to the participation of PLC, a higher decrease in oocyte activation was detected when cells were exposed to neomycin. Inhibition of PC-PLC with D609 and IP-PLC with U73122 indicated that the last PLC has a significant participation in the effect of DhL-induced activation. Results would indicate that DhL induces activation of in vitro matured oocytes of Rhinella arenarum by activation of IP-PLC, which in turn may induce IP3 formation which produces Ca2+ release.

  10. Activation of Raf/MEK/ERK/cPLA2 signaling pathway is essential for chlamydial acquisition of host glycerophospholipids.

    PubMed

    Su, Heng; McClarty, Grant; Dong, Feng; Hatch, Grant M; Pan, Zhixing K; Zhong, Guangming

    2004-03-01

    Chlamydiae, a diverse group of obligate intracellular pathogens replicating within cytoplasmic vacuoles of eukaryotic cells, are able to acquire lipids from host cells. Here we report that activation of the host Raf-MEK-ERK-cPLA2 signaling cascade is required for the chlamydial uptake of host glycerophospholipids. Both the MAP kinase pathway (Ras/Raf/MEK/ERK) and Ca(2+)-dependent cytosolic phospholipase A2 (cPLA2) were activated in chlamydia-infected cells. The inhibition of cPLA2 activity resulted in the blockade of the chlamydial uptake of host glycerophospholipids and impairment in chlamydial growth. Blocking either c-Raf-1 or MEK1/2 activity prevented the chlamydial activation of ERK1/2, leading to the suppression of both chlamydial activation of the host cPLA2 and uptake of glycerophospholipids from the host cells. The chlamydia-induced phosphorylation of cPLA2 was also blocked by a dominant negative ERK2. Furthermore, activation of both ERK1/2 and cPLA2 was dependent on chlamydial growth and restricted within chlamydia-infected cells, suggesting an active manipulation of the host ERK-cPLA2 signaling pathway by chlamydiae.

  11. Inhibitory effect of pinostrobin from Renealmia alpinia, on the enzymatic and biological activities of a PLA2.

    PubMed

    Gómez-Betancur, Isabel; Pereañez, Jaime Andrés; Patiño, Arley Camilo; Benjumea, Dora

    2016-08-01

    Pinostrobin is a flavanone isolated from Renealmia alpinia, a plant used in folk medicine to treat snakebites. We tested the inhibitory ability of pinostrobin on the enzymatic, anticoagulant, myotoxic and edema-inducing activities of a PLA2 isolated from Crotalus durissus cumanensis venom. The compound displayed IC50 values of 1.76mM and 1.85mM (95% Confidence intervals: 1.34-2.18 and 1.21-2.45) on the PLA2 enzymatic activity, when either aggregated or monodispersed substrates were used, respectively. When mice were injected with PLA2 preincubated with 0.4, 2.0 and 4.0mM of pinostrobin, myotoxic activity induced by the PLA2 was inhibited up to 87%. Nevertheless, these values decreased up to 56% when the pinostrobin was injected into muscle after PLA2. Pinostrobin inhibited edema-forming and anticoagulant activities of the PLA2. In order to have insights on the mode of action of pinostrobin, intrinsic fluorescence and ultraviolet studies were performed. Results suggest that pinostrobin interacts directly with the PLA2. These findings were supported by molecular docking results, which suggested that pinostrobin forms hydrogen bonds with residues His48 and Asp49 of PLA2, besides, a π-π stacking interactions with those of residues Phe5 and Trp31, and rings C of flavanone and Tyr52 of the toxin. PMID:27109758

  12. Cloning and expression of biologically active Plantago lanceolata pollen allergen Pla l 1 in the yeast Pichia pastoris.

    PubMed Central

    Calabozo, Belén; Díaz-Perales, Araceli; Salcedo, Gabriel; Barber, Domingo; Polo, Florentino

    2003-01-01

    The glycoprotein Pla l 1 is the major allergen from English plantain (Plantago lanceolata) pollen, which is a common cause of pollinosis in temperate areas. Three complete cDNAs for Pla l 1 isoforms were isolated by PCR using specific 3' and 5' primers. All three Pla l 1 cDNAs code for a 25-residue leader peptide and a 131-residue mature protein that contains two polymorphic positions, an N-glycosylation site at position 107 and six cysteine residues involved in three disulphide bridges. The allergen variant Pla l 1.0101 was produced in Pichia pastoris at a yield of 20 mg per litre of culture as a mixture of non-glycosylated (17 kDa), glycosylated (23 kDa) and dimeric (32-39 kDa) forms. Recombinant Pla l 1 (rPla l 1) was purified by affinity chromatography with an anti-natural Pla l 1 (anti-nPla l 1) monoclonal antibody, and its molecular and immunological properties were compared with the natural allergen by CD spectroscopic analysis, enzymic deglycosylation, lectin-binding assay, immunodetection and ELISA-inhibition assays using sera from plantain-allergic patients. The recombinant allergen is properly folded, as deduced from CD spectra, and the immunodominant allergenic epitopes of the natural allergen are preserved in rPla l 1. These results allow us to conclude that P. pastoris is a convenient system for the efficient production of biologically active rPla l 1, which could have a potential use for clinical purposes. Furthermore, a sequence similarity of Pla l 1 to the major allergen from the olive tree pollen, Ole e 1, is revealed in this work, and the allergenic cross-reactivity between both allergens has been studied. PMID:12646046

  13. Cloning and expression of biologically active Plantago lanceolata pollen allergen Pla l 1 in the yeast Pichia pastoris.

    PubMed

    Calabozo, Belén; Díaz-Perales, Araceli; Salcedo, Gabriel; Barber, Domingo; Polo, Florentino

    2003-06-15

    The glycoprotein Pla l 1 is the major allergen from English plantain (Plantago lanceolata) pollen, which is a common cause of pollinosis in temperate areas. Three complete cDNAs for Pla l 1 isoforms were isolated by PCR using specific 3' and 5' primers. All three Pla l 1 cDNAs code for a 25-residue leader peptide and a 131-residue mature protein that contains two polymorphic positions, an N-glycosylation site at position 107 and six cysteine residues involved in three disulphide bridges. The allergen variant Pla l 1.0101 was produced in Pichia pastoris at a yield of 20 mg per litre of culture as a mixture of non-glycosylated (17 kDa), glycosylated (23 kDa) and dimeric (32-39 kDa) forms. Recombinant Pla l 1 (rPla l 1) was purified by affinity chromatography with an anti-natural Pla l 1 (anti-nPla l 1) monoclonal antibody, and its molecular and immunological properties were compared with the natural allergen by CD spectroscopic analysis, enzymic deglycosylation, lectin-binding assay, immunodetection and ELISA-inhibition assays using sera from plantain-allergic patients. The recombinant allergen is properly folded, as deduced from CD spectra, and the immunodominant allergenic epitopes of the natural allergen are preserved in rPla l 1. These results allow us to conclude that P. pastoris is a convenient system for the efficient production of biologically active rPla l 1, which could have a potential use for clinical purposes. Furthermore, a sequence similarity of Pla l 1 to the major allergen from the olive tree pollen, Ole e 1, is revealed in this work, and the allergenic cross-reactivity between both allergens has been studied.

  14. Synthesis of Leucas Aspera Extract Loaded Gold-PLA-PEG-PLA Amphiphilic Copolymer Nanoconjugates: In Vitro Cytotoxicity and Anti-Inflammatory Activity Studies.

    PubMed

    Reena, K; Balashanmugam, P; Gajendiran, M; Antony, S Arul

    2016-05-01

    Gold nanoparticles (GNPs) are synthesized using the medicinal plant Leucas Aspera extract (LAE) and poly lactic acid-co-poly ethylene glycol-co-poly lactic acid (PLA-PEG-PLA) copolymer by water-in-oil (W/O) emulsion method. The proposed method of W/O emulsion technique involves synthesis of GNPs and loading of Leucas Aspera extract on to the PLA-PEG-PLA copolymer matrix simultaneously. The synthesized GNPs are characterized by Fourier transform infra-red (FTIR) spectroscopy, dynamic light scattering (DLS), X-ray diffractometry (XRD) and transmission electron microscopy (TEM). The GNPs-LAE loaded polymer NPs are examined for the in vitro cytotoxicity on South African green monkey's kidney cells. The GNPs-LAE loaded polymer nanoconjugates exhibit maximum up to 95% of cell viability with 100 μg concentration of GNPs in the sample. The GNPs-LAE loaded polymer NPs exhibit better anti-inflammatory activity when compared to the pure LAE. PMID:27483820

  15. Synthesis of Leucas Aspera Extract Loaded Gold-PLA-PEG-PLA Amphiphilic Copolymer Nanoconjugates: In Vitro Cytotoxicity and Anti-Inflammatory Activity Studies.

    PubMed

    Reena, K; Balashanmugam, P; Gajendiran, M; Antony, S Arul

    2016-05-01

    Gold nanoparticles (GNPs) are synthesized using the medicinal plant Leucas Aspera extract (LAE) and poly lactic acid-co-poly ethylene glycol-co-poly lactic acid (PLA-PEG-PLA) copolymer by water-in-oil (W/O) emulsion method. The proposed method of W/O emulsion technique involves synthesis of GNPs and loading of Leucas Aspera extract on to the PLA-PEG-PLA copolymer matrix simultaneously. The synthesized GNPs are characterized by Fourier transform infra-red (FTIR) spectroscopy, dynamic light scattering (DLS), X-ray diffractometry (XRD) and transmission electron microscopy (TEM). The GNPs-LAE loaded polymer NPs are examined for the in vitro cytotoxicity on South African green monkey's kidney cells. The GNPs-LAE loaded polymer nanoconjugates exhibit maximum up to 95% of cell viability with 100 μg concentration of GNPs in the sample. The GNPs-LAE loaded polymer NPs exhibit better anti-inflammatory activity when compared to the pure LAE.

  16. The effect of polyhexamethylene guanidine hydrochloride (PHMG) derivatives introduced into polylactide (PLA) on the activity of bacterial enzymes.

    PubMed

    Walczak, Maciej; Richert, Agnieszka; Burkowska-But, Aleksandra

    2014-11-01

    The present study was aimed at investigating bactericidal properties of polylactide (PLA) films containing three different polyhexamethylene guanidine hydrochloride (PHMG) derivatives and effect of the derivatives on extracellular hydrolytic enzymes and intracellular dehydrogenases. All PHMG derivatives had a slightly stronger bactericidal effect on Staphylococcus aureus than on E. coli but only PHMG granular polyethylene wax (at the concentration of at least 0.6 %) has a bactericidal effect. PHMG derivatives introduced into PLA affected the activity of microbial hydrolases to a small extent. This means that the introduction of PHMG derivatives into PLA will not reduce its enzymatic biodegradation significantly. On the other hand, PHMG derivatives introduced into PLA strongly affected dehydrogenases activity in S. aureus than in E. coli.

  17. Bp-13 PLA2: Purification and Neuromuscular Activity of a New Asp49 Toxin Isolated from Bothrops pauloensis Snake Venom

    PubMed Central

    Sucasaca-Monzón, Georgina; Randazzo-Moura, Priscila; Rocha, Thalita; Vilca-Quispe, Augusto; Ponce-Soto, Luis Alberto; Marangoni, Sérgio; da Cruz-Höfling, Maria Alice; Rodrigues-Simioni, Léa

    2015-01-01

    A new PLA2 (Bp-13) was purified from Bothrops pauloensis snake venom after a single chromatographic step of RP-HPLC on μ-Bondapak C-18. Amino acid analysis showed a high content of hydrophobic and basic amino acids and 14 half-cysteine residues. The N-terminal sequence showed a high degree of homology with basic Asp49 PLA2 myotoxins from other Bothrops venoms. Bp-13 showed allosteric enzymatic behavior and maximal activity at pH 8.1, 36°–45°C. Full Bp-13 PLA2 activity required Ca2+; its PLA2 activity was inhibited by Mg2+, Mn2+, Sr2+, and Cd2+ in the presence and absence of 1 mM Ca2+. In the mouse phrenic nerve-diaphragm (PND) preparation, the time for 50% paralysis was concentration-dependent (P < 0.05). Both the replacement of Ca2+ by Sr2+ and temperature lowering (24°C) inhibited the Bp-13 PLA2-induced twitch-tension blockade. Bp-13 PLA2 inhibited the contractile response to direct electrical stimulation in curarized mouse PND preparation corroborating its contracture effect. In biventer cervicis preparations, Bp-13 induced irreversible twitch-tension blockade and the KCl evoked contracture was partially, but significantly, inhibited (P > 0.05). The main effect of this new Asp49 PLA2 of Bothrops pauloensis venom is on muscle fiber sarcolemma, with avian preparation being less responsive than rodent preparation. The study enhances biochemical and pharmacological characterization of B. pauloensis venom. PMID:25789175

  18. In vitro study of the PLA2 inhibition and antioxidant activities of Aloe vera leaf skin extracts

    PubMed Central

    2011-01-01

    Background In the present work we determined the total phenolic content of Aloe vera leaf skin (AVLS) extracts by using various solvents (hexane, chloroform-ethanol (1/1), ethyl acetate, butanol and water). We have also evaluated the antioxidant and the anti-PLA2 properties of these extracts by measuring their inhibition potency on the human pro-inflammatory phospholipase A2 (group IIA). Results The water extract exhibits the highest inhibitory effect with an IC50 = 0.22 mg/ml and interestingly no effect was observed on the digestive phospholipase A2 (group IB) even at a concentration of 5 mg/ml. Antioxidant activities were also analyzed and the most active extracts were observed when using chloroform ethanol (1/1) and ethyl acetate (IC50 = 0.274 and 0.326 mg/ml, respectively). Analysis of the total phenolic content reveals that the water extract, with the best anti-PLA2 effect, was poor in phenolic molecules (2 mg GAE/g). This latter value has to be compared with the chloroform-ethanol and the ethyl acetate extracts (40 and 23.8 mg GAE/g, respectively), mostly responsible for the antioxidant activity. Conclusion A significant correlation was established between the total phenolic content and the antioxidant capacity but not with the anti PLA2 activity. Results from phytochemical screening suggest that the anti PLA2 molecules were probably catechin tannins compounds. PMID:21310091

  19. The Determinants for the Enzyme Activity of Human Parvovirus B19 Phospholipase A2 (PLA2) and Its Influence on Cultured Cells

    PubMed Central

    Yi, Qianhui; Huang, Yu; Zhao, Dan; Yang, Yongbo; Tijssen, Peter; Qiu, Jianming; Liu, Kaiyu; Li, Yi

    2013-01-01

    Human parvovirus B19 (B19V) is the causative agent of erythema infectiosum in humans. B19 infection also causes severe disease manifestations, such as chronic anemia in immunocompromised patients, aplastic crisis in patients with a high turnover rate of red blood cells, and hydrops fetalis in pregnant women. Although a secreted phospholipase A2 (PLA2) motif has been identified in the unique region of the B19V minor capsid protein VP1(VP1u), the determinants for its enzyme activity and its influences on host cells are not well understood. The purpose of this study was to investigate the contribution of the PLA2 motif and other regions of the VP1u to the PLA2 activity, to determine the cellular localization of the VP1u protein, and to examine the effects of VP1u on cellular cytokines. We found that in addition to the critical conserved and non-conserved amino acids within the VP1u PLA2 motif, amino acid residues outside the VP1u PLA2 motif are also important for the PLA2 activity. VP1u and various mutants all revealed a nucleo-cytoplasmic distribution. UT7-Epo cells treated with prokaryotic expressed VP1u or mutant proteins with PLA2 activity released a large amount of free fatty acid (FFA), and the cell morphological change occurred dramatically. However, neither free fatty acid nor cell morphology change occurred for cells treated with the mutants without PLA2 activity. The wild type and the VP1u mutants with the PLA2 activity also activated TNF-α promoter and upregulated the transcription activity of NF-κB in transfected cells. In addition, we found that the amino acids outside the PLA2 domain are critical for the viral PLA2 activity, and that these tested VP1u mutants did not affect the localization of the VP1u protein. PMID:23596524

  20. The determinants for the enzyme activity of human parvovirus B19 phospholipase A2 (PLA2) and its influence on cultured cells.

    PubMed

    Deng, Xuefeng; Dong, Yanming; Yi, Qianhui; Huang, Yu; Zhao, Dan; Yang, Yongbo; Tijssen, Peter; Qiu, Jianming; Liu, Kaiyu; Li, Yi

    2013-01-01

    Human parvovirus B19 (B19V) is the causative agent of erythema infectiosum in humans. B19 infection also causes severe disease manifestations, such as chronic anemia in immunocompromised patients, aplastic crisis in patients with a high turnover rate of red blood cells, and hydrops fetalis in pregnant women. Although a secreted phospholipase A2 (PLA2) motif has been identified in the unique region of the B19V minor capsid protein VP1(VP1u), the determinants for its enzyme activity and its influences on host cells are not well understood. The purpose of this study was to investigate the contribution of the PLA2 motif and other regions of the VP1u to the PLA2 activity, to determine the cellular localization of the VP1u protein, and to examine the effects of VP1u on cellular cytokines. We found that in addition to the critical conserved and non-conserved amino acids within the VP1u PLA2 motif, amino acid residues outside the VP1u PLA2 motif are also important for the PLA2 activity. VP1u and various mutants all revealed a nucleo-cytoplasmic distribution. UT7-Epo cells treated with prokaryotic expressed VP1u or mutant proteins with PLA2 activity released a large amount of free fatty acid (FFA), and the cell morphological change occurred dramatically. However, neither free fatty acid nor cell morphology change occurred for cells treated with the mutants without PLA2 activity. The wild type and the VP1u mutants with the PLA2 activity also activated TNF-α promoter and upregulated the transcription activity of NF-κB in transfected cells. In addition, we found that the amino acids outside the PLA2 domain are critical for the viral PLA2 activity, and that these tested VP1u mutants did not affect the localization of the VP1u protein.

  1. Effect of cellulose and lignin on disintegration, antimicrobial and antioxidant properties of PLA active films.

    PubMed

    Yang, W; Fortunati, E; Dominici, F; Giovanale, G; Mazzaglia, A; Balestra, G M; Kenny, J M; Puglia, D

    2016-08-01

    This study reports the effects on antimicrobial, antioxidant, migration and disintegrability activities of ternary nanocomposite films based on poly(lactic acid) incorporating two biobased nanofillers, (cellulose nanocrystals (CNC) and lignin nanoparticles (LNP)), in two different amounts (1 and 3% wt.). Results from antimicrobial tests revealed a capacity to inhibit the Gram negative bacterial growth of Xanthomonas axonopodis pv. vesicatoria and Xanthomonas arboricola pv. pruni along the time, offering innovative opportunities against dangerous bacterial plant pathogens. LNP proved to be highly efficient in antioxidation activity, based on the disappearance of the absorption band at 517nm of the free radical, 2,2-diphenyl-1-picrylhydrazyl (DPPH) upon reduction by an antiradical compound; moreover the combination of LNP and CNC generates a synergistic positive effect in the antioxidation response of PLA ternary films. Furthermore, all the studied formulations showed a disintegrability value up to 90% after 15days of incubation in composting conditions. Migration results showed that the films can be considered suitable for application in food packaging field. PMID:27126170

  2. Sustained activation of proton channels and NADPH oxidase in human eosinophils and murine granulocytes requires PKC but not cPLAactivity

    PubMed Central

    Morgan, Deri; Cherny, Vladimir V; Finnegan, Alison; Bollinger, James; Gelb, Michael H; DeCoursey, Thomas E

    2007-01-01

    The prevailing hypothesis that a signalling pathway involving cPLA2α is required to enhance the gating of the voltage-gated proton channel associated with NADPH oxidase was tested in human eosinophils and murine granulocytes. This hypothesis invokes arachidonic acid (AA) liberated by cPLA2α as a final activator of proton channels. In human eosinophils studied in the perforated-patch configuration, phorbol myristate acetate (PMA) stimulation elicited NADPH oxidase-generated electron current (Ie) and enhanced proton channel gating identically in the presence or absence of three specific cPLA2α inhibitors, Wyeth-1, pyrrolidine-2 and AACOCF3 (arachidonyl trifluoromethyl ketone). In contrast, PKC inhibitors GFX (GF109203X) or staurosporine prevented the activation of either proton channels or NADPH oxidase. PKC inhibition during the respiratory burst reversed the activation of both molecules, suggesting that ongoing phosphorylation is required. This effect of GFX was inhibited by okadaic acid, implicating phosphatases in proton channel deactivation. Proton channel activation by AA was partially reversed by GFX or staurosporine, indicating that AA effects are due in part to activation of PKC. In granulocytes from mice with the cPLA2α gene disrupted (knockout mice), PMA or fMetLeuPhe activated NADPH oxidase and proton channels in a manner indistinguishable from the responses of control cells. Thus, cPLA2α is not essential to activate the proton conductance or for a normal respiratory burst. Instead, phosphorylation of the proton channel or an activating molecule converts the channel to its activated gating mode. The existing paradigm for regulation of the concerted activity of proton channels and NADPH oxidase must be revised. PMID:17185330

  3. Modulation of the pharmacological effects of enzymatically-active PLA2 by BTL-2, an isolectin isolated from the Bryothamnion triquetrum red alga

    PubMed Central

    Oliveira, Simone CB; Fonseca, Fabiana V; Antunes, Edson; Camargo, Enilton A; Morganti, Rafael P; Aparício, Ricardo; Toyama, Daniela O; Beriam, Luís OS; Nunes, Eudismar V; Cavada, Benildo S; Nagano, Celso S; Sampaio, Alexandre H; Nascimento, Kyria S; Toyama, Marcos H

    2008-01-01

    Background An interaction between lectins from marine algae and PLA2 from rattlesnake was suggested some years ago. We, herein, studied the effects elicited by a small isolectin (BTL-2), isolated from Bryothamnion triquetrum, on the pharmacological and biological activities of a PLA2 isolated from rattlesnake venom (Crotalus durissus cascavella), to better understand the enzymatic and pharmacological mechanisms of the PLA2 and its complex. Results This PLA2 consisted of 122 amino acids (approximate molecular mass of 14 kDa), its pI was estimated to be 8.3, and its amino acid sequence shared a high degree of similarity with that of other neurotoxic and enzymatically-active PLA2s. BTL-2 had a molecular mass estimated in approximately 9 kDa and was characterized as a basic protein. In addition, BTL-2 did not exhibit any enzymatic activity. The PLA2 and BTL-2 formed a stable heterodimer with a molecular mass of approximately 24–26 kDa, estimated by molecular exclusion HPLC. In the presence of BTL-2, we observed a significant increase in PLA2 activity, 23% higher than that of PLA2 alone. BTL-2 demonstrated an inhibition of 98% in the growth of the Gram-positive bacterial strain, Clavibacter michiganensis michiganensis (Cmm), but only 9.8% inhibition of the Gram-negative bacterial strain, Xanthomonas axonopodis pv passiflorae (Xap). PLA2 decreased bacterial growth by 27.3% and 98.5% for Xap and Cmm, respectively, while incubating these two proteins with PLA2-BTL-2 inhibited their growths by 36.2% for Xap and 98.5% for Cmm. PLA2 significantly induced platelet aggregation in washed platelets, whereas BTL-2 did not induce significant platelet aggregation in any assay. However, BTL-2 significantly inhibited platelet aggregation induced by PLA2. In addition, PLA2 exhibited strong oedematogenic activity, which was decreased in the presence of BTL-2. BTL-2 alone did not induce oedema and did not decrease or abolish the oedema induced by the 48/80 compound. Conclusion The

  4. Clinical usefulness of autoantibodies to M-type phospholipase A2 receptor (PLA2R) for monitoring disease activity in idiopathic membranous nephropathy (IMN).

    PubMed

    Radice, Antonella; Trezzi, Barbara; Maggiore, Umberto; Pregnolato, Francesca; Stellato, Tiziana; Napodano, Pietro; Rolla, Davide; Pesce, Gianpaola; D'Amico, Marco; Santoro, Domenico; Londrino, Francesco; Ravera, Federica; Ortisi, Giuseppe; Sinico, Renato Alberto

    2016-02-01

    Autoantibodies to M-type phospholipase A2 receptor (PLA2R) are specific markers of idiopathic membranous nephropathy (IMN). They can differentiate IMN from other glomerular diseases and primary from secondary forms of MN. Preliminary data suggest that anti-PLA2R antibody titer correlates with disease activity but more solid evidence is needed. To evaluate the performance of anti-PLA2R antibody for monitoring nephropathy activity, 149 anti-PLA2R antibody measurements were performed during the follow-up of 42 biopsy proven IMN consecutive patients. Patients were enrolled either at time of diagnosis (33 cases, inception cohort) or after diagnosis (9 patients, non-inception cohort). Anti-PLA2R detection was performed using the highly sensitive transfected cell-based indirect immunofluorescence (IIFT). Over the follow-up there was a linear time-trend of decreasing proteinuria (P<0.001), increasing serum albumin (P<0.001) and decreasing PLA2R antibody levels (P=0.002). There was a statistically significant association between changes in PLA2R antibody levels and the clinical course of PLA2R-positive IMN. The positive PLA2R serum antibody status was linearly associated with increasing proteinuria and decreasing serum albumin over time, compared with negative antibody status. Moreover, the strong correlation between the clinical conditions and PLA2R antibody levels allowed the prediction of prevalence distribution of patients with active disease, partial and complete remission. Over the course of the follow-up, the probability of halving proteinuria increased 6.5 times after disappearance of PLA2R antibodies. Our data suggest that the serial evaluation of anti-PLA2R antibodies could help in optimal timing and duration of the immunosuppressive therapy, reducing over(under)-treatment and associated side-effects.

  5. Hubble Space Telescope Observations of Active Asteroid 324P/La Sagra

    NASA Astrophysics Data System (ADS)

    Jewitt, David; Agarwal, Jessica; Weaver, Harold; Mutchler, Max; Li, Jing; Larson, Stephen

    2016-09-01

    Hubble Space Telescope observations of active asteroid 324P/La Sagra near perihelion show continued mass loss consistent with the sublimation of near-surface ice. Isophotes of the coma measured from a vantage point below the orbital plane are best matched by steady emission of particles having a nominal size of a ˜ 100 μm. The inferred rate of mass loss, dM d /dt ˜ 0.2 kg s-1, can be supplied by sublimation of water ice in thermal equilibrium with sunlight from an area as small as 930 m2, corresponding to about 0.2% of the nucleus surface. Observations taken from a vantage point only 0.°6 from the orbital plane of 324P set a limit to the velocity of ejection of dust in the direction perpendicular to the plane, V ⊥ < 1 m s-1. Short-term photometric variations of the near-nucleus region, if related to rotation of the underlying nucleus, rule-out periods ≤3.8 hr and suggest that rotation probably does not play a central role in driving the observed mass loss. We estimate that, in the previous orbit, 324P lost about 4 × 107 kg in dust particles, corresponding to 6 × 10-5 of the mass of a 550 m spherical nucleus of assumed density ρ = 1000 kg m-3. If continued, mass loss at this rate would limit the lifetime of 324P to ˜1.6 × 104 orbits (about 105 years). To survive for the 100-400 Myr timescales corresponding to dynamical and collisional stability requires a duty cycle of 2 × 10-4 ≤ f d ≤ 8 × 10-4. Unless its time in orbit is overestimated by many orders of magnitude, 324P is revealed as a briefly active member of a vast population of otherwise dormant ice-containing asteroids.

  6. Hubble Space Telescope Observations of Active Asteroid 324P/La Sagra

    NASA Astrophysics Data System (ADS)

    Jewitt, David; Agarwal, Jessica; Weaver, Harold; Mutchler, Max; Li, Jing; Larson, Stephen

    2016-09-01

    Hubble Space Telescope observations of active asteroid 324P/La Sagra near perihelion show continued mass loss consistent with the sublimation of near-surface ice. Isophotes of the coma measured from a vantage point below the orbital plane are best matched by steady emission of particles having a nominal size of a ∼ 100 μm. The inferred rate of mass loss, dM d /dt ∼ 0.2 kg s‑1, can be supplied by sublimation of water ice in thermal equilibrium with sunlight from an area as small as 930 m2, corresponding to about 0.2% of the nucleus surface. Observations taken from a vantage point only 0.°6 from the orbital plane of 324P set a limit to the velocity of ejection of dust in the direction perpendicular to the plane, V ⊥ < 1 m s‑1. Short-term photometric variations of the near-nucleus region, if related to rotation of the underlying nucleus, rule-out periods ≤3.8 hr and suggest that rotation probably does not play a central role in driving the observed mass loss. We estimate that, in the previous orbit, 324P lost about 4 × 107 kg in dust particles, corresponding to 6 × 10‑5 of the mass of a 550 m spherical nucleus of assumed density ρ = 1000 kg m‑3. If continued, mass loss at this rate would limit the lifetime of 324P to ∼1.6 × 104 orbits (about 105 years). To survive for the 100–400 Myr timescales corresponding to dynamical and collisional stability requires a duty cycle of 2 × 10‑4 ≤ f d ≤ 8 × 10‑4. Unless its time in orbit is overestimated by many orders of magnitude, 324P is revealed as a briefly active member of a vast population of otherwise dormant ice-containing asteroids.

  7. Human single-chain urokinase is activated by the omptins PgtE of Salmonella enterica and Pla of Yersinia pestis despite mutations of active site residues.

    PubMed

    Järvinen, Hanna M; Laakkonen, Liisa; Haiko, Johanna; Johansson, Tiira; Juuti, Katri; Suomalainen, Marjo; Buchrieser, Carmen; Kalkkinen, Nisse; Korhonen, Timo K

    2013-08-01

    Fibrinolysis is important in cell migration and tightly regulated by specific inhibitors and activators; of the latter, urokinase (uPA) associates with enhancement of cell migration. Active uPA is formed through cleavage of the single-chain uPA (scuPA). The Salmonella enterica strain 14028R cleaved human scuPA at the peptide bond Lys158-Ile159, the site cleaved also by the physiological activator human plasmin. The cleavage led to activation of scuPA, while no cleavage or activation were detected with the mutant strain 14028R lacking the omptin protease PgtE. Complementation and expression studies confirmed the role of PgtE in scuPA activation. Similar cleavage and activation of scuPA were detected with recombinant Escherichia coli expressing the omptin genes pla from Yersinia pestis, ompT and ompP from E. coli, sopA from Shigella flexneri, and leo from Legionella pneumophila. For these omptins the activation of scuPA is the only shared function so far detected. Only poor cleavage and activation of scuPA were seen with YcoA of Y. pestis and YcoB of Yersinia pseudotuberculosis that are considered to be proteolytically inactive omptin variants. Point mutations of active site residues in Pla and PgtE had different effects on the proteolysis of plasminogen and of scuPA, indicating versatility in omptin proteolysis.

  8. PPAR Activation Induces M1 Macrophage Polarization via cPLA2-COX-2 Inhibition, Activating ROS Production against Leishmania mexicana

    PubMed Central

    Díaz-Gandarilla, J. A.; Osorio-Trujillo, C.; Hernández-Ramírez, V. I.; Talamás-Rohana, P.

    2013-01-01

    Defence against Leishmania depends upon Th1 inflammatory response and, a major problem in susceptible models, is the turnoff of the leishmanicidal activity of macrophages with IL-10, IL-4, and COX-2 upregulation, as well as immunosuppressive PGE2, all together inhibiting the respiratory burst. Peroxisome proliferator-activated receptors (PPAR) activation is responsible for macrophages polarization on Leishmania susceptible models where microbicide functions are deactivated. In this paper, we demonstrated that, at least for L. mexicana, PPAR activation, mainly PPARγ, induced macrophage activation through their polarization towards M1 profile with the increase of microbicide activity against intracellular pathogen L. mexicana. PPAR activation induced IL-10 downregulation, whereas the production of proinflammatory cytokines such as TNF-α, IL-1β, and IL-6 remained high. Moreover, PPAR agonists treatment induced the deactivation of cPLA2-COX-2-prostaglandins pathway together with an increase in TLR4 expression, all of whose criteria meet the M1 macrophage profile. Finally, parasite burden, in treated macrophages, was lower than that in infected nontreated macrophages, most probably associated with the increase of respiratory burst in these treated cells. Based on the above data, we conclude that PPAR agonists used in this work induces M1 macrophages polarization via inhibition of cPLA2 and the increase of aggressive microbicidal activity via reactive oxygen species (ROS) production. PMID:23555077

  9. The anti-inflammatory activity of standard aqueous stem bark extract of Mangifera indica L. as evident in inhibition of Group IA sPLA2.

    PubMed

    Dhananjaya, Bhadrapura Lakkappa; Shivalingaiah, Sudharshan

    2016-03-01

    The standard aqueous stem bark extract is consumed as herbal drink and used in the pharmaceutical formulations to treat patients suffering from various disease conditions in Cuba. This study was carried out to evaluate the modulatory effect of standard aqueous bark extract of M. indica on Group IA sPLA2. M. indica extract, dose dependently inhibited the GIA sPLA2 (NN-XIa-PLA2) activity with an IC50 value 8.1 µg/ml. M. indica extract effectively inhibited the indirect hemolytic activity up to 98% at ~40 µg/ml concentration and at various concentrations (0-50 µg/ml), it dose dependently inhibited the edema formation. When examined as a function of increased substrate and calcium concentration, there was no relieve of inhibitory effect on the GIA sPLA2. Furthermore, the inhibition was irreversible as evidenced from binding studies. It is observed that the aqueous extract ofM. indica effectively inhibits sPLA2 and it is associated inflammatory activities, which substantiate their anti-inflammatory properties. The mode of inhibition could be due to direct interaction of components present in the extract, with sPLA2 enzyme. Further studies on understanding the principal constituents, responsible for the anti-inflammatory activity would be interesting to develop this into potent anti-inflammatory agent. PMID:26959323

  10. Increased iPLA2 activity and levels of phosphorylated GSK3B in platelets are associated with donepezil treatment in Alzheimer's disease patients.

    PubMed

    Talib, L L; Hototian, S R; Joaquim, H P G; Forlenza, O V; Gattaz, W F

    2015-12-01

    Reduced phospholipase A2 (PLA2) activity and increased phosphorylation of glycogen synthase kinase 3B (GSK3B) participate in the production of beta-amyloid plaques and of neurofibrillary tangles, which are two neuropathological hallmarks of Alzheimer's disease (AD). Experimental evidences suggest a neuroprotective effect of the cholinesterase inhibitor donepezil in the treatment the disease. The aims of the present study were to evaluate in AD patients the effects of treatment with donepezil on PLA2 activity and GSK3B level. Thirty patients with AD were treated during 6 months with 10 mg daily of donepezil. Radio-enzymatic assays were used to measure PLA2 activity and Elisa assays for GSK3B level, both in platelets. Before treatment and after 3 and 6 months on donepezil, AD patients underwent a cognitive assessment and platelet samples were collected. Values were compared to a healthy control group of 42 sex- and age-matched elderly individuals. Before treatment, iPLA2 activity was lower in patients with AD as compared to controls (p < 0.001). At baseline, no differences were found in GSK3B level between both groups. After 3 and 6 months of treatment, we found a significant increase in iPLA2 activity (p = 0.015 and p < 0.001, respectively). iPLA2 increment was related to the cognitive improvement during treatment (p = 0.037). After 6 months, we found an increase in phosphorylated GSK3B (p = 0.02). The present findings suggest two possible mechanisms by which donepezil delays the progression of AD. The increment of iPLA2 activity may reduce the production of beta-amyloid plaques, whereas the phosphorylation of GSK3B inactivates the enzyme, reducing thus the phosphorylation of tau protein. PMID:25920742

  11. Increased iPLA2 activity and levels of phosphorylated GSK3B in platelets are associated with donepezil treatment in Alzheimer's disease patients.

    PubMed

    Talib, L L; Hototian, S R; Joaquim, H P G; Forlenza, O V; Gattaz, W F

    2015-12-01

    Reduced phospholipase A2 (PLA2) activity and increased phosphorylation of glycogen synthase kinase 3B (GSK3B) participate in the production of beta-amyloid plaques and of neurofibrillary tangles, which are two neuropathological hallmarks of Alzheimer's disease (AD). Experimental evidences suggest a neuroprotective effect of the cholinesterase inhibitor donepezil in the treatment the disease. The aims of the present study were to evaluate in AD patients the effects of treatment with donepezil on PLA2 activity and GSK3B level. Thirty patients with AD were treated during 6 months with 10 mg daily of donepezil. Radio-enzymatic assays were used to measure PLA2 activity and Elisa assays for GSK3B level, both in platelets. Before treatment and after 3 and 6 months on donepezil, AD patients underwent a cognitive assessment and platelet samples were collected. Values were compared to a healthy control group of 42 sex- and age-matched elderly individuals. Before treatment, iPLA2 activity was lower in patients with AD as compared to controls (p < 0.001). At baseline, no differences were found in GSK3B level between both groups. After 3 and 6 months of treatment, we found a significant increase in iPLA2 activity (p = 0.015 and p < 0.001, respectively). iPLA2 increment was related to the cognitive improvement during treatment (p = 0.037). After 6 months, we found an increase in phosphorylated GSK3B (p = 0.02). The present findings suggest two possible mechanisms by which donepezil delays the progression of AD. The increment of iPLA2 activity may reduce the production of beta-amyloid plaques, whereas the phosphorylation of GSK3B inactivates the enzyme, reducing thus the phosphorylation of tau protein.

  12. Leptin suppresses non-apoptotic cell death in ischemic rat cardiomyocytes by reduction of iPLA{sub 2} activity

    SciTech Connect

    Takatani-Nakase, Tomoka Takahashi, Koichi

    2015-07-17

    Caspase-independent, non-apoptotic cell death is an important therapeutic target in myocardial ischemia. Leptin, an adipose-derived hormone, is known to exhibit cytoprotective effects on the ischemic heart, but the mechanisms are poorly understood. In this research, we found that pretreatment of leptin strongly suppressed ischemic-augmented nuclear shrinkage and non-apoptotic cell death on cardiomyocytes. Leptin was also shown to significantly inhibit the activity of iPLA{sub 2}, which is considered to play crucial roles in non-apoptotic cell death, resulting in effective prevention of ischemia-induced myocyte death. These findings provide the first evidence of a protective mechanism of leptin against ischemia-induced non-apoptotic cardiomyocyte death. - Highlights: • Myocardial ischemia-model induces in caspase-independent, non-apoptotic cell death. • Leptin strongly inhibits ischemic-augmented non-apoptotic cell death. • Leptin reduces iPLA{sub 2} activity, leading to avoidance of non-apoptotic cell death.

  13. Interactions of pharmacologically active snake venom sPLA2 with different cell lines

    PubMed Central

    Doumanov, Jordan; Mladenova, Kirilka; Aleksandrov, Radoslav; Danovski, Georgi; Petrova, Svetla

    2014-01-01

    Secreted Phospholipases A2 (sPLA2s) represent a large family of structurally related enzymes, which target different tissues and organs and induce numerous pharmacological effects based on their catalytic specificity – hydrolysis of the sn-2 ester bond of glycerophospholipids. The neurotoxin vipoxin, isolated from the venom of Vipera ammodytes meriodionalis, is a heterodimeric postsynaptic ionic complex composed of two protein subunits – a basic and toxic His48 sPLA2 enzyme and an acidic, enzymatically inactive and non-toxic component. In this paper, for the first time, we demonstrate that vipoxin sPLA2 enzyme affects cell integrity and viability of four cell types and causes different cell responses. The most dramatic local tissue effects were observed with RPE-1 (retinal pigment epithelial) cells followed by A549 (adenocarcinomic human alveolar epithelial) cells and MDCK (Madin-Darby Canine Kidney epithelial) cells. Products of the enzymatic reaction, lysophospholipids and unsaturated free fatty acids, act as lipid mediators that can induce membrane damaging or can stimulate cell proliferation. Our preliminary results on the cytotoxic effect of vipoxin sPLA2 on A549 cells are promising in searching of its eventual anticancer potential. PMID:26019578

  14. Replacing with whole grains and legumes reduces Lp-PLA2 activities in plasma and PBMCs in patients with prediabetes or T2D1

    PubMed Central

    Kim, Minjoo; Jeung, Se Ri; Jeong, Tae-Sook; Lee, Sang-Hyun; Lee, Jong Ho

    2014-01-01

    To determine dietary effects on circulating lipoprotein-associated phospholipase A2 (Lp-PLA2) activity and enzyme activity in peripheral blood mononuclear cells (PBMCs), 99 patients with impaired fasting glucose, impaired glucose tolerance, or newly-diagnosed T2D were randomly assigned to either a control group (usual diet with refined rice) or the whole grain and legume group. Substitution of whole grains and legumes for refined rice was associated with the replacement of 7% of energy from carbohydrates with energy from protein (about 4%) and fat. After 12 weeks, the whole grain and legume group showed a significant decrease in fasting glucose, insulin, homeostasis model assessment-insulin resistance, hemoglobin A1c, malondialdehyde, plasma Lp-PLA2 activity, and oxidized LDL (ox-LDL), and an increase in LDL particle size. The changes (Δs) in these variables in the whole grain and legume group were significantly different from those in controls after adjustment for the baseline levels. When all subjects were considered, Δ plasma Lp-PLA2 positively correlated with Δ glucose, Δ PBMC Lp-PLA2, Δ ox-LDL, and Δ urinary 8-epi-prostaglandin F2α after being adjusted for confounding factors. The Δ PBMC Lp-PLA2 correlated positively with Δ glucose and Δ ox-LDL, and negatively with Δ LDL particle size and baseline PBMC Lp-PLA2. The substitution of whole grains and legumes for refined rice resulted in a reduction in Lp-PLA2 activities in plasma and PBMCs partly through improved glycemic control, increased consumption of protein relative to carbohydrate, and reduced lipid peroxides. PMID:24904022

  15. Lipid distribution and phospholipase A/sub 2/ (PLA/sub 2/) activity in skeletal muscle from malignant hyperthermia (MH) susceptible and normal pigs

    SciTech Connect

    Fletcher, J.E.; Rosenberg, H.; Michaux, K.; Tripolitis, L.; Cheah, K.S.; Cheah, A.M.

    1987-05-01

    The authors examined the lipid distribution and PLA2 activity of skeletal muscle from three pigs in each of three phenotypic groups. The three groups did not differ in respect to total FFA, cholesterol, triglycerides, or total lipid phosphorus. The distributions of phospholipids, as determined by 2-D TLC and phosphorus quantification, and fatty acids, as determined by 1-D TLC and GC, were also similar. When muscle homogenates were incubated with radiolabeled Triton/phosphatidylcholine mixed micelles to measure PLA2 activity, three groups could be distinguished by percent of total radiolabel that was FFA: MH+, 4.9 +/- 0.3%; MH +/-, 3.4 +/- 0.3%; MH-, 1.0 +/- 0.1%. Therefore, MH susceptible pigs differ from normals in having elevated PLA2 activity, which is evident in incubated muscle homogenates, but not intact tissue.

  16. sPLA2 -IIA Overexpression in Mice Epidermis Depletes Hair Follicle Stem Cells and Induces Differentiation Mediated Through Enhanced JNK/c-Jun Activation.

    PubMed

    Sarate, Rahul M; Chovatiya, Gopal L; Ravi, Vagisha; Khade, Bharat; Gupta, Sanjay; Waghmare, Sanjeev K

    2016-09-01

    Secretory phospholipase A2 Group-IIA (sPLA2 -IIA) catalyzes the hydrolysis of the sn-2 position of glycerophospholipids to yield fatty acids and lysophospholipids. sPLA2 -IIA is deregulated in various cancers; however, its role in hair follicle stem cell (HFSC) regulation is obscure. Here we report a transgenic mice overexpressing sPLA2 -IIA (K14-sPLA2 -IIA) showed depletion of HFSC pool. This was accompanied with increased differentiation, loss of ortho-parakeratotic organization and enlargement of sebaceous gland, infundibulum and junctional zone. The colony forming efficiency of keratinocytes was significantly reduced. Microarray profiling of HFSCs revealed enhanced level of epithelial mitogens and transcription factors, c-Jun and FosB that may be involved in proliferation and differentiation. Moreover, K14-sPLA2 -IIA keratinocytes showed enhanced activation of EGFR and JNK1/2 that led to c-Jun activation, which co-related with enhanced differentiation. Further, depletion of stem cells in bulge is associated with high levels of chromatin silencing mark, H3K27me3 and low levels of an activator mark, H3K9ac suggestive of alteration in gene expression contributing toward stem cells differentiation. Our results, first time uncovered that overexpression of sPLA2 -IIA lead to depletion of HFSCs and differentiation associated with altered histone modification. Thus involvement of sPLA2 -IIA in stem cells regulation and disease pathogenesis suggest its prospective clinical implications. Stem Cells 2016;34:2407-2417. PMID:27299855

  17. sPLA2 -IIA Overexpression in Mice Epidermis Depletes Hair Follicle Stem Cells and Induces Differentiation Mediated Through Enhanced JNK/c-Jun Activation.

    PubMed

    Sarate, Rahul M; Chovatiya, Gopal L; Ravi, Vagisha; Khade, Bharat; Gupta, Sanjay; Waghmare, Sanjeev K

    2016-09-01

    Secretory phospholipase A2 Group-IIA (sPLA2 -IIA) catalyzes the hydrolysis of the sn-2 position of glycerophospholipids to yield fatty acids and lysophospholipids. sPLA2 -IIA is deregulated in various cancers; however, its role in hair follicle stem cell (HFSC) regulation is obscure. Here we report a transgenic mice overexpressing sPLA2 -IIA (K14-sPLA2 -IIA) showed depletion of HFSC pool. This was accompanied with increased differentiation, loss of ortho-parakeratotic organization and enlargement of sebaceous gland, infundibulum and junctional zone. The colony forming efficiency of keratinocytes was significantly reduced. Microarray profiling of HFSCs revealed enhanced level of epithelial mitogens and transcription factors, c-Jun and FosB that may be involved in proliferation and differentiation. Moreover, K14-sPLA2 -IIA keratinocytes showed enhanced activation of EGFR and JNK1/2 that led to c-Jun activation, which co-related with enhanced differentiation. Further, depletion of stem cells in bulge is associated with high levels of chromatin silencing mark, H3K27me3 and low levels of an activator mark, H3K9ac suggestive of alteration in gene expression contributing toward stem cells differentiation. Our results, first time uncovered that overexpression of sPLA2 -IIA lead to depletion of HFSCs and differentiation associated with altered histone modification. Thus involvement of sPLA2 -IIA in stem cells regulation and disease pathogenesis suggest its prospective clinical implications. Stem Cells 2016;34:2407-2417.

  18. Enhanced anticancer activity of DM1-loaded star-shaped folate-core PLA-TPGS nanoparticles

    NASA Astrophysics Data System (ADS)

    Tang, Xiaolong; Liang, Yong; Zhu, Yongqiang; Cai, Shiyu; Sun, Leilei; Chen, Tianyi

    2014-10-01

    The efficient delivery of therapeutic drugs into interested cells is a critical challenge to broad application of nonviral vector systems. In this research, emtansine (DM1)-loaded star-shaped folate-core polylactide- d-α-tocopheryl polyethylene glycol 1000 succinate (FA-PLA-TPGS-DM1) copolymer which demonstrated superior anticancer activity in vitro/ vivo in comparison with linear FA-PLA-TPGS nanoparticles was applied to be a vector of DM1 for FR+ breast cancer therapy. The DM1- or coumarin 6-loaded nanoparticles were fabricated, and then characterized in terms of size, morphology, drug encapsulation efficiency, and in vitro drug release. And the viability of MCF-7/HER2 cells treated with FA-DM1-nanoparticles (NPs) was assessed. Severe combined immunodeficient mice carrying MCF-7/HER2 tumor xenografts were treated in several groups including phosphate-buffered saline control, DM1, DM1-NPs, and FA-DM1-NPs. The antitumor activity was then assessed by survival time and solid tumor volume. All the specimens were prepared for formalin-fixed and paraffin-embedded tissue sections for hematoxylin-eosin staining. The data showed that the FA-DM1-NPs could efficiently deliver DM1 into MCF-7/HER2 cells. The cytotoxicity of DM1 to MCF-7/HER2 cells was significantly increased by FA-DM1-NPs when compared with the control groups. In conclusion, the FA-DM1-NPs offered a considerable potential formulation for FR+ tumor-targeting biotherapy.

  19. Influence of obesity and cardiometabolic makers on lipoprotein-associated phospholipase A2 (Lp-PLA2) activity in adolescents: the healthy young cross-sectional study

    PubMed Central

    2013-01-01

    Background Lipoprotein-associated phospholipase A2 activity (Lp-PLA2) is a good marker of cardiovascular risk in adults. It is strongly associated with stroke and many others cardiovascular events. Despite this, the impact of obesity on this enzyme activity and its relation to biomarkers of cardiovascular disease in adolescents is not very well investigated. The purpose of this article is to evaluate the influence of obesity and cardiometabolic markers on Lp-PLA2 activity in adolescents. Results This cross-sectional study included 242 adolescents (10–19 years) of both gender. These subjects were classified in Healthy Weight (n = 77), Overweight (n = 82) and Obese (n = 83) groups. Lipid profile, glucose, insulin, HDL size, LDL(−) and anti-LDL(−) antibodies were analyzed. The Lp-PLA2 activity was determined by a colorimetric commercial kit. Body mass index (BMI), waist circumference and body composition were monitored. Food intake was evaluated using three 24-hour diet recalls. The Lp-PLA2 activity changed in function to high BMI, waist circumference and fat mass percentage. It was also positively associated with HOMA-IR, glucose, insulin and almost all variables of lipid profile. Furthermore, it was negatively related to Apo AI (β = −0.137; P = 0.038) and strongly positively associated with Apo B (β = 0.293; P < 0.001) and with Apo B/Apo AI ratio (β = 0.343; P < 0.001). The better predictor model for enzyme activity, on multivariate analysis, included Apo B/Apo AI (β = 0.327; P < 0.001), HDL size (β = −0.326; P < 0.001), WC (β = 0.171; P = 0.006) and glucose (β = 0.119; P = 0.038). Logistic regression analysis demonstrated that changes in Apo B/Apo AI ratio were associated with a 73.5 times higher risk to elevated Lp-PLA2 activity. Conclusions Lp-PLA2 changes in function of obesity, and that it shows important associations with markers of cardiovascular risk, in particular with

  20. A Transcription Factor γMYB1 Binds to the P1BS cis-Element and Activates PLA2-γ Expression with its Co-Activator γMYB2.

    PubMed

    Nguyen, Ha Thi Kim; Kim, Soo Youn; Cho, Kwang-Moon; Hong, Jong Chan; Shin, Jeong Sheop; Kim, Hae Jin

    2016-04-01

    Phospholipase A2(PLA2) hydrolyzes phospholipid molecules to produce two products that are both precursors of second messengers of signaling pathways and signaling molecules per se.Arabidopsis thaliana PLA2 paralogs (-β,-γ and -δ) play critical roles during pollen development, pollen germination and tube growth. In this study, analysis of the PLA2-γ promoter using a deletion series revealed that the promoter region -153 to -1 is crucial for its pollen specificity. Using a yeast one-hybrid screening assay with the PLA2-γ promoter and an Arabidopsis transcription factor (TF)-only library, we isolated two novel MYB-like TFs belonging to the MYB-CC family, denoted here as γMYB1 and γMYB2. By electrophoretic mobility shift assay, we found that these two TFs bind directly to the P1BS (phosphate starvation response 1-binding sequence)cis-element of the PLA2-γ promoter. γMYB1 alone functioned as a transcriptional activator for PLA2-γ expression, whereas γMYB2 directly interacted with γMYB1 and enhanced its activation. Overexpression of γMYB1 in the mature pollen grain led to increased expression of not only the PLA2-γ gene but also of several genes whose promoters contain the P1BS cis-element and which are involved in the Pi starvation response, phospholipid biosynthesis and sugar synthesis. Based on these results, we suggest that the TF γMYB1 binds to the P1BS cis-element, activates the expression of PLA2-γ with the assistance of its co-activator, γMYB2, and regulates the expression of several target genes involved in many plant metabolic reactions. PMID:26872838

  1. Isolation and characterization of ellagic acid derivatives isolated from Casearia sylvestris SW aqueous extract with anti-PLA(2) activity.

    PubMed

    Da Silva, Saulo L; Calgarotto, Andrana K; Chaar, Jamal S; Marangoni, Sérgio

    2008-11-01

    The Casearia sylvestris SW (Flacourtiaceae) is utilized in folk medicine (Brazil and all Latin American) to treat several pathologic processes as inflammation, cancer, microbial infection and snake bites. Studies showed that C. sylvestris aqueous extract can inhibit many toxic effects caused by snake venoms (or caused by phospholipase A(2) isolated) from different species, mainly of Bothrops genus. Inhibition of enzymatic and myotoxic activities, decrease of edema formation and increase of the survival rate of rats injected with lethal doses of bothropic venoms are some toxic effects inhibited by C. sylvestris. In this study, four ellagic acid derivatives from aqueous extracts of C. sylvestris were isolated, characterized, and tested against effects from both total venom and PLA(2) (Asp 49 BthTX-II) from the venom of Bothrops jararacussu. The isolated compounds were as follows: ellagic acid (A), 3'-O-methyl ellagic acid (B), 3,3'-di-O-methyl ellagic acid (C), 3-O-methyl-3',4'-methylenedioxy ellagic acid (D). The inhibition constant values (Ki) for enzymatic activity, as well the IC(50) values found in the edematogenic and myotoxic activities, indicate that the ellagic acid is the best inhibitor of these activities, while compounds C and D are the substances with lowest capacity on inhibiting these same effects. Our results show that the presence of hydroxyls at position 3 or 3' (compounds A and B) increases the capacity of these derivatives on inhibiting these toxic effects. However, the presence of methoxyl groups at position 3 or 3' reduced, but did not completely inhibit the capacity of compounds C and D on inhibiting all the toxic effects studied.

  2. Cross-talk between p(38)MAPK and G iα in regulating cPLA 2 activity by ET-1 in pulmonary smooth muscle cells.

    PubMed

    Chakraborti, Sajal; Chowdhury, Animesh; Chakraborti, Tapati

    2015-02-01

    Endothelin-1 (ET-1) is known as the most potent vasoconstrictor yet described. Infusion of ET-1 into isolated rabbit lung has been shown to cause pulmonary vasoconstriction with the involvement of arachidonic acid metabolites. Given the potency of arachidonic acid metabolites, the activity of phospholipase A2 must be tightly regulated. Herein, we determined the mechanisms by which ET-1 stimulates cPLA2 activity during ET-1 stimulation of bovine pulmonary artery smooth muscle cells. We demonstrated that (i) treatment of bovine pulmonary artery smooth muscle cells with ET-1 stimulates cPLA2 activity in the cell membrane; (ii) ET-1 caused increase in O 2 (·-) production occurs via NADPH oxidase-dependent mechanism; (iii) ET-1-stimulated NADPH oxidase activity is markedly prevented upon pretreatment with PKC-ζ inhibitor, indicating that PKC-ζ plays a prominent role in this scenario; (iv) ET-1-induced NADPH oxidase-derived O 2 (·-) stimulates an aprotinin sensitive protease activity due to prominent increase in [Ca(2+)]i; (v) the aprotinin sensitive protease plays a pivotal role in activating PKC-α, which in turn phosphorylates p(38)MAPK and subsequently Giα leading to the activation of cPLA2. Taken together, we suggest that cross-talk between p(38)MAPK and Giα with the involvement of PKC-ζ, NADPH oxidase-derived O 2 (·-) , [Ca(2+)]i, aprotinin-sensitive protease and PKC-α play a pivotal role for full activation of cPLA2 during ET-1 stimulation of pulmonary artery smooth muscle cells.

  3. Chain length specificity for activation of cPLA2alpha by C1P: use of the dodecane delivery system to determine lipid-specific effects.

    PubMed

    Wijesinghe, Dayanjan S; Subramanian, Preeti; Lamour, Nadia F; Gentile, Luciana B; Granado, Maria H; Bielawska, Alicja; Szulc, Zdzislaw; Gomez-Munoz, Antonio; Chalfant, Charles E

    2009-10-01

    Previously, our laboratory demonstrated that ceramide-1-phosphate (C1P) specifically activated group IVA cytosolic phospholipase A(2) (cPLA(2)alpha) in vitro. In this study, we investigated the chain length specificity of this interaction. C1P with an acyl-chain of >or=6 carbons efficiently activated cPLA(2)alpha in vitro, whereas C(2)-C1P, was unable to do so. Delivery of C1P to cells via the newly characterized ethanol/dodecane system demonstrated a lipid-specific activation of cPLA(2)alpha, AA release, and PGE(2) synthesis (EC(50) = 400 nM) when compared to structurally similar lipids. C1P delivered as vesicles in water also induced a lipid-specific increase in AA release. Mass spectrometric analysis demonstrated that C1P delivered via ethanol/dodecane induced a 3-fold increase in endogenous C1P with little metabolism to ceramide. C1P was also more efficiently delivered (>3-fold) to internal membranes by ethanol/dodecane as compared to vesiculated C1P. Using this now established delivery method for lipids, C(2)-C1P was shown to be ineffective in the induction of AA release as compared with C(6)-C1P, C(16)-C1P, and C(18:1) C1P. Here, we demonstrate that C1P requires >or=6 carbon acyl-chain to activate cPLA(2)alpha. Thus, published reports on the biological activity of C(2)-C1P are not via eicosanoid synthesis. Furthermore, this study demonstrates that the alcohol/dodecane system can be used to efficiently deliver exogenous phospholipids to cells for the examination of specific biological effects.

  4. Plasticized poly(lactic acid)-poly(hydroxybutyrate) (PLA-PHB) blends incorporated with catechin intended for active food-packaging applications.

    PubMed

    Arrieta, Marina Patricia; Castro-López, María del Mar; Rayón, Emilio; Barral-Losada, Luis Fernando; López-Vilariño, José Manuel; López, Juan; González-Rodríguez, María Victoria

    2014-10-15

    Active biobased packaging materials based on poly(lactic acid)-poly(hydroxybutyrate) (PLA-PHB) blends were prepared by melt blending and fully characterized. Catechin incorporation, as antioxidant compound, enhanced the thermal stability, whereas its release was improved by the addition of acetyl(tributyl citrate) (ATBC) as plasticizer. Whereas the incorporation of ATBC resulted in a reduction of elastic modulus and hardness, catechin addition produced more rigid materials due to hydrogen-bonding interactions between catechin hydroxyl groups and carbonyl groups of PLA and PHB. The quantification of catechin released into a fatty food simulant and the antioxidant effectiveness after the release process were demonstrated. The effect of the materials' exposure to a food simulant was also investigated. PHB-added materials maintained their structural and mechanical properties after 10 days in a test medium that represents the worst foreseeable conditions of the intended use. Thus, plasticized PLA-PHB blends with catechin show their potential as biobased active packaging for fatty food. PMID:25255375

  5. Plasticized poly(lactic acid)-poly(hydroxybutyrate) (PLA-PHB) blends incorporated with catechin intended for active food-packaging applications.

    PubMed

    Arrieta, Marina Patricia; Castro-López, María del Mar; Rayón, Emilio; Barral-Losada, Luis Fernando; López-Vilariño, José Manuel; López, Juan; González-Rodríguez, María Victoria

    2014-10-15

    Active biobased packaging materials based on poly(lactic acid)-poly(hydroxybutyrate) (PLA-PHB) blends were prepared by melt blending and fully characterized. Catechin incorporation, as antioxidant compound, enhanced the thermal stability, whereas its release was improved by the addition of acetyl(tributyl citrate) (ATBC) as plasticizer. Whereas the incorporation of ATBC resulted in a reduction of elastic modulus and hardness, catechin addition produced more rigid materials due to hydrogen-bonding interactions between catechin hydroxyl groups and carbonyl groups of PLA and PHB. The quantification of catechin released into a fatty food simulant and the antioxidant effectiveness after the release process were demonstrated. The effect of the materials' exposure to a food simulant was also investigated. PHB-added materials maintained their structural and mechanical properties after 10 days in a test medium that represents the worst foreseeable conditions of the intended use. Thus, plasticized PLA-PHB blends with catechin show their potential as biobased active packaging for fatty food.

  6. Platelet activating factor (PAF) antagonists on cytokine induction of iNOS and sPLA2 in immortalized astrocytes (DITNC).

    PubMed

    Wang, J H; Sun, G Y

    2000-05-01

    Platelet-activating factor (PAF, 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) and its receptor are known to play important roles in modulating neuronal plasticity and inflammatory responses, particularly during neuronal injury. PAF receptors are widespread in different brain regions and are present on the cell surface as well as in intracellular membrane compartments. Astrocytes are immune active cells and are responsive to cytokines, which stimulate signaling cascades leading to transcriptional activation of genes and protein synthesis. Our recent studies indicate the ability of cytokines, e.g., tumor necrosis factor-alpha (TNFalpha), interleukin-1beta (IL-1beta) and interferon-gamma (IFNgamma), to induce the inducible nitric oxide (iNOS) and secretory phospholipase A2 (sPLA2) genes in immortalized astrocytes (DITNC) (Li et al., J. Interferon and Cytokine Res. 19: 121-127. 1999). The main objective for this study is to examine the effects of PAF antagonists on cytokine induction of iNOS and sPLA2 in these cells. Results show that BN50730, a synthetic PAF antagonist, but not BN52021, a natural PAF antagonist (ginkolide B) can dose-dependently inhibit cytokine induction of NO production and sPLA2 release. Inhibition of NO production by BN50730 corroborated well with the decrease in iNOS protein and mRNA levels as well as binding of NF-kappaB STAT- 1 to DNA, suggesting that BN50730 action is upstream of the transcriptional process. These results are in agreement with the role of intracellular PAF in regulating the cytokine signaling cascade in astrocytes and further suggest the possible use of BN50730 as a therapeutic agent for suppressing the inflammatory pathways elicited by cytokines. PMID:10905622

  7. COX-2 and sPLA2 inhibitory activity of aqueous extract and polyphenols of Rhizophora mangle (red mangrove).

    PubMed

    Marrero, Evangelina; Sánchez, Janet; de Armas, Elizabeth; Escobar, Arturo; Melchor, Gleiby; Abad, M J; Bermejo, Paulina; Villar, Angel M; Megías, J; Alcaraz, Maria J

    2006-06-01

    The aqueous extract of Rhizophora mangle bark and its polyphenolic fractions showed remarkable in vitro antiinflammatory activity in a preliminary study. The low molecular weight fraction exhibited cyclooxygenase-2 inhibitory activity while the total aqueous extract and the low molecular weight fraction showed secretory phospholipase A(2) inhibitory activity. PMID:16698195

  8. AdipoR-increased intracellular ROS promotes cPLA2 and COX-2 expressions via activation of PKC and p300 in adiponectin-stimulated human alveolar type II cells.

    PubMed

    Chen, Hsiao-Mei; Yang, Chuen-Mao; Chang, Jia-Feng; Wu, Chi-Sheng; Sia, Kee-Chin; Lin, Wei-Ning

    2016-08-01

    Adiponectin, an adipokine, accumulated in lung system via T-cadherin after allergens/ozone challenge. However, the roles of adiponectin on lung pathologies were controversial. Here we reported that adiponectin stimulated expression of inflammatory proteins, cytosolic phospholipase A2 (cPLA2), cyclooxygenase-2 (COX-2), and production of reactive oxygen species (ROS) in human alveolar type II A549 cells. AdipoR1/2 involved in adiponectin-activated NADPH oxidase and mitochondria, which further promoted intracellular ROS accumulation. Protein kinase C (PKC) may involve an adiponectin-activated NADPH oxidase. Similarly, p300 phosphorylation and histone H4 acetylation occurred in adiponectin-challenged A549 cells. Moreover, adiponectin-upregulated cPLA2 and COX-2 expression was significantly abrogated by ROS scavenger (N-acetylcysteine) or the inhibitors of NADPH oxidase (apocynin), mitochondrial complex I (rotenone), PKC (Ro31-8220, Gö-6976, and rottlerin), and p300 (garcinol). Briefly, we reported that adiponectin stimulated cPLA2 and COX-2 expression via AdipoR1/2-dependent activation of PKC/NADPH oxidase/mitochondria resulting in ROS accumulation, p300 phosphorylation, and histone H4 acetylation. These results suggested that adiponectin promoted lung inflammation, resulting in exacerbation of pulmonary diseases via upregulating cPLA2 and COX-2 expression together with intracellular ROS production. Understanding the adiponectin signaling pathways on regulating cPLA2 and COX-2 may help develop therapeutic strategies on pulmonary diseases. PMID:27288489

  9. Active targeting docetaxel-PLA nanoparticles eradicate circulating lung cancer stem-like cells and inhibit liver metastasis.

    PubMed

    Yang, Nan; Jiang, Yao; Zhang, Huifeng; Sun, Bo; Hou, Chunying; Zheng, Ji; Liu, Yanyong; Zuo, Pingping

    2015-01-01

    Lung cancer is the major cause of cancer related lethality worldwide, and metastasis to distant organs is the pivotal cause of death for the vast majority of lung cancer patients. Accumulated evidence indicates that lung cancer stem-like cells (CSLCs) play important roles in metastagenesis, and these circulating CSLCs may be important targets to inhibit the subsequent metastasis. The present study was aimed at establishing CSLC-targeting polylactic acid (PLA) encapsulated docetaxel nanoparticles for antimetastatic therapy. Cyclic binding peptides were screened on CSLCs in vitro and the peptide CVKTPAQSC exhibiting high specific binding ability to pulmonary adenocarcinoma tissue was subsequently conjugated to the nanoparticles loaded with docetaxel (NDTX). Antimetastatic effect of CSLC-targeting nanoparticles loaded with docetaxel (TNDTX) was evaluated in a nude mouse model of liver metastasis. Results showed that, in the absence of targeting peptide, NDTX hardly exhibited any antimetastatic effect. However, TNDTX treatment significantly decreased the metastatic tumor area in the nude mouse liver. Histopathological and serological results also confirmed the antimetastatic efficacy of TNDTX. To our knowledge, this is the first report on establishing a CSLC-based strategy for lung cancer metastatic treatment, and we hope this will offer a potential therapeutic approach for management of metastatic lung cancer.

  10. PLA coated paper containing active inorganic nanoparticles: Material characterization and fate of nanoparticles in the paper recycling process.

    PubMed

    Zhang, Hai; Bussini, Daniele; Hortal, Mercedes; Elegir, Graziano; Mendes, Joana; Jordá Beneyto, Maria

    2016-06-01

    For paper and paperboard packaging, recyclability plays an important role in conserving the resources and reducing the environmental impacts. Therefore, when it comes to the nano-enabled paper packaging material, the recyclability issue should be properly addressed. This study represents our first report on the fate of nanomaterials in paper recycling process. The packaging material of concern is a PLA (Polylactic Acid) coated paper incorporating zinc oxide nanoparticles in the coating layer. The material was characterised and assessed in a lab-scale paper recycling line. The recyclability test was based on a method adapted from ATICELCA MC501-13, which enabled to recover over 99% of the solids material. The mass balance result indicates that 86-91% zinc oxide nanoparticles ended up in the rejected material stream, mostly embedded within the polymer coating; whereas 7-16% nanoparticles ended up in the accepted material stream. Besides, the tensile strength of the recycled handsheets suggests that the nano-enabled coating had no negative impacts on the recovered fibre quality.

  11. PLA coated paper containing active inorganic nanoparticles: Material characterization and fate of nanoparticles in the paper recycling process.

    PubMed

    Zhang, Hai; Bussini, Daniele; Hortal, Mercedes; Elegir, Graziano; Mendes, Joana; Jordá Beneyto, Maria

    2016-06-01

    For paper and paperboard packaging, recyclability plays an important role in conserving the resources and reducing the environmental impacts. Therefore, when it comes to the nano-enabled paper packaging material, the recyclability issue should be properly addressed. This study represents our first report on the fate of nanomaterials in paper recycling process. The packaging material of concern is a PLA (Polylactic Acid) coated paper incorporating zinc oxide nanoparticles in the coating layer. The material was characterised and assessed in a lab-scale paper recycling line. The recyclability test was based on a method adapted from ATICELCA MC501-13, which enabled to recover over 99% of the solids material. The mass balance result indicates that 86-91% zinc oxide nanoparticles ended up in the rejected material stream, mostly embedded within the polymer coating; whereas 7-16% nanoparticles ended up in the accepted material stream. Besides, the tensile strength of the recycled handsheets suggests that the nano-enabled coating had no negative impacts on the recovered fibre quality. PMID:27036997

  12. Circulating (CD3−CD19+CD20−IgD−CD27highCD38high) Plasmablasts: A Promising Cellular Biomarker for Immune Activity for Anti-PLA2R1 Related Membranous Nephropathy?

    PubMed Central

    Beukinga, Ingrid; Willard-Gallo, Karen; Nortier, Joëlle; Pradier, Olivier

    2016-01-01

    Membranous nephropathy (MN) is a kidney specific autoimmune disease mainly mediated by anti-phospholipase A2 receptor 1 autoantibody (PLA2R1 Ab). The adequate assessment of chimeric anti-CD20 monoclonal antibody, rituximab (RTX), efficacy is still needed to improve clinical outcome of patient with MN. We evaluated the modification of plasmablasts (CD3−CD19+CD20−IgD−CD27highCD38high), a useful biomarker of RTX response in other autoimmune diseases, and memory (CD3−CD19+CD20+IgD−CD27+CD38−) and naive (CD3−CD19+CD20+IgD+CD27−CD38low) B cells by fluorescence-activated cell sorter analysis in PLA2R1 related MN in one patient during the 4 years of follow-up after RTX. RTX induced complete disappearance of CD19+ B cells, plasmablasts, and memory B cells as soon as day 15. Despite severe CD19+ lymphopenia, plasmablasts and memory B cells reemerged early before naive B cells (days 45, 90, and 120, resp.). During the follow-up, plasmablasts decreased more rapidly than memory B cells but still remained elevated as compared to day 0 of RTX. Concomitantly, anti-PLA2R1 Ab increased progressively. Our single case report suggests that, besides monitoring of serum anti-PLA2R1 Ab level, enumeration of circulating plasmablasts and memory B cells represents an attractive and complementary tool to assess immunological activity and efficacy of RTX induced B cells depletion in anti-PLA2R1 Ab related MN. PMID:27493452

  13. Novel Nanodimension artificial red blood cells that act as O2 and CO2 carrier with enhanced antioxidant activity: PLA-PEG nanoencapsulated PolySFHb-superoxide dismutase-catalase-carbonic anhydrase

    PubMed Central

    Gao, Wei; Bian, Yuzhu; Chang, Thomas M.S.

    2013-01-01

    Poly(ethylene glycol)-Poly(lactic acid) block-copolymer (PEG-PLA) was prepared and characterized using Fourier transform infrared spectrophotometer (FTIR). Glutaraldehyde was used to crosslink stroma-free hemoglobin (SFHb), superoxide dismutase (SOD), catalase (CAT), and carbonic anhydrase (CA) into a soluble complex of PolySFHb-SOD-CAT-CA. PEG-PLA was then used to nanoencapsulated PolySFHb-SOD-CAT-CA by oil in water emulsification. This resulted in the formation of PLA-PEG-PolySFHb-SOD-CAT-CA nanocapsules that have enhanced antioxidant activity and that can transport both O2 and CO2. These are homogeneous particles with an average diameter of 100 nm with good dispersion and core shell structure, high entrapment efficiency (EE%), and nanocapsule percent recovery. A lethal hemorrhagic shock model in rats was used to evaluate the therapeutic effect of the PLA-PEG-PolySFHb-SOD-CAT-CA nanocapsules. Infusion of this preparation resulted in the lowering of the elevated tissue PCO2 and also recovery of the mean arterial pressure (MAP). PMID:23336597

  14. Proinflammatory secreted phospholipase A2 type IIA (sPLA-IIA) induces integrin activation through direct binding to a newly identified binding site (site 2) in integrins αvβ3, α4β1, and α5β1.

    PubMed

    Fujita, Masaaki; Zhu, Kan; Fujita, Chitose K; Zhao, Min; Lam, Kit S; Kurth, Mark J; Takada, Yoko K; Takada, Yoshikazu

    2015-01-01

    Integrins are activated by signaling from inside the cell (inside-out signaling) through global conformational changes of integrins. We recently discovered that fractalkine activates integrins in the absence of CX3CR1 through the direct binding of fractalkine to a ligand-binding site in the integrin headpiece (site 2) that is distinct from the classical RGD-binding site (site 1). We propose that fractalkine binding to the newly identified site 2 induces activation of site 1 though conformational changes (in an allosteric mechanism). We reasoned that site 2-mediated activation of integrins is not limited to fractalkine. Human secreted phospholipase A2 type IIA (sPLA2-IIA), a proinflammatory protein, binds to integrins αvβ3 and α4β1 (site 1), and this interaction initiates a signaling pathway that leads to cell proliferation and inflammation. Human sPLA2-IIA does not bind to M-type receptor very well. Here we describe that sPLA2-IIA directly activated purified soluble integrin αvβ3 and transmembrane αvβ3 on the cell surface. This activation did not require catalytic activity or M-type receptor. Docking simulation predicted that sPLA2-IIA binds to site 2 in the closed-headpiece of αvβ3. A peptide from site 2 of integrin β1 specifically bound to sPLA2-IIA and suppressed sPLA2-IIA-induced integrin activation. This suggests that sPLA2-IIA activates αvβ3 through binding to site 2. sPLA2-IIA also activated integrins α4β1 and α5β1 in a site 2-mediated manner. We recently identified small compounds that bind to sPLA2-IIA and suppress integrin-sPLA2-IIA interaction (e.g. compound 21 (Cmpd21)). Cmpd21 effectively suppressed sPLA2-IIA-induced integrin activation. These results define a novel mechanism of proinflammatory action of sPLA2-IIA through integrin activation. PMID:25398877

  15. Activities.

    ERIC Educational Resources Information Center

    Kincaid, Charlene; And Others

    1993-01-01

    Presents an activity in which students collect and organize data from a real-world simulation of the scientific concept of half life. Students collect data using a marble sifter, analyze the data using a graphing calculator, and determine an appropriate mathematical model. Includes reproducible worksheets. (MDH)

  16. Activities.

    ERIC Educational Resources Information Center

    Mathematics Teacher, 1982

    1982-01-01

    The material presented is designed to help students explore geometric patterns involving Fibonnaci numbers and the golden ratio, and to aid in review of basic geometry skills. Worksheet masters intended for duplication are provided. Suggestions are made of possible classroom extensions to the initial activities. (MP)

  17. Total chemical synthesis of enzymatically active human type II secretory phospholipase A2

    PubMed Central

    Hackeng, Tilman M.; Mounier, Carine M.; Bon, Cassian; Dawson, Philip E.; Griffin, John H.; Kent, Stephen B. H.

    1997-01-01

    Human group II secretory phospholipase A2 (sPLA2) is an enzyme found in the α granules of platelets and at inflammatory sites. Although its physiological function is unclear, sPLA2 can inhibit blood coagulation reactions independent of its lipolytic action. To study the molecular basis of PLA2 activities, we developed a total chemical synthesis of sPLA2 by chemical ligation of large unprotected peptides. The synthetic segments PLA2-(1–58)-αCOSCH2COOH and PLA2-(59–124) were prepared by stepwise solid-phase peptide synthesis and ligated to yield a peptide bond between Gly58 and Cys59. The 124-residue polypeptide product (mass: 13,920 ± 2 Da) was folded to yield one major product (mass: 13,905 ± 1 Da), the loss of 15 ± 3 Da reflecting the formation of seven disulfide bonds. Circular dichroism studies of synthetic sPLA2 showed α-helix, β-structure, and random coil contents consistent with those found in the crystal structure of sPLA2. Synthetic sPLA2 had kcat and Km values identical to those of recombinant sPLA2 for hydrolysis of 1,2-bis(heptanoylthio)-phosphatidylcholine. Synthetic sPLA2, like recombinant sPLA2, inhibited thrombin generation from prothrombinase complex (factors Xa, V, II, Ca2+, and phospholipids). In the absence of phospholipids, both synthetic and recombinant sPLA2 inhibited by 70% prothrombin activation by factors Xa, Va, and Ca2+. Thus, synthetic sPLA2 is a phospholipid-independent anticoagulant like recombinant or natural sPLA2. This study demonstrates that chemical synthesis of sPLA2 yields a fully active native-like enzyme and offers a straightforward tool to provide sPLA2 analogs for structure–activity studies of anticoagulant, lipolytic, or inflammatory activities. PMID:9223275

  18. sPLA2 IB induces human podocyte apoptosis via the M-type phospholipase A2 receptor

    PubMed Central

    Pan, Yangbin; Wan, Jianxin; Liu, Yipeng; Yang, Qian; Liang, Wei; Singhal, Pravin C.; Saleem, Moin A.; Ding, Guohua

    2014-01-01

    The M-type phospholipase A2 receptor (PLA2R) is expressed in podocytes in human glomeruli. Group IB secretory phospholipase A2 (sPLA2 IB), which is one of the ligands of the PLA2R, is more highly expressed in chronic renal failure patients than in controls. However, the roles of the PLA2R and sPLA2 IB in the pathogenesis of glomerular diseases are unknown. In the present study, we found that more podocyte apoptosis occurs in the kidneys of patients with higher PLA2R and serum sPLA2 IB levels. In vitro, we demonstrated that human podocyte cells expressed the PLA2R in the cell membrane. After binding with the PLA2R, sPLA2 IB induced podocyte apoptosis in a time- and concentration-dependent manner. sPLA2 IB-induced podocyte PLA2R upregulation was not only associated with increased ERK1/2 and cPLA2α phosphorylation but also displayed enhanced apoptosis. In contrast, PLA2R-silenced human podocytes displayed attenuated apoptosis. sPLA2 IB enhanced podocyte arachidonic acid (AA) content in a dose-dependent manner. These data indicate that sPLA2 IB has the potential to induce human podocyte apoptosis via binding to the PLA2R. The sPLA2 IB-PLA2R interaction stimulated podocyte apoptosis through activating ERK1/2 and cPLA2α and through increasing the podocyte AA content. PMID:25335547

  19. sPLA2 IB induces human podocyte apoptosis via the M-type phospholipase A2 receptor.

    PubMed

    Pan, Yangbin; Wan, Jianxin; Liu, Yipeng; Yang, Qian; Liang, Wei; Singhal, Pravin C; Saleem, Moin A; Ding, Guohua

    2014-01-01

    The M-type phospholipase A2 receptor (PLA2R) is expressed in podocytes in human glomeruli. Group IB secretory phospholipase A2 (sPLA2 IB), which is one of the ligands of the PLA2R, is more highly expressed in chronic renal failure patients than in controls. However, the roles of the PLA2R and sPLA2 IB in the pathogenesis of glomerular diseases are unknown. In the present study, we found that more podocyte apoptosis occurs in the kidneys of patients with higher PLA2R and serum sPLA2 IB levels. In vitro, we demonstrated that human podocyte cells expressed the PLA2R in the cell membrane. After binding with the PLA2R, sPLA2 IB induced podocyte apoptosis in a time- and concentration-dependent manner. sPLA2 IB-induced podocyte PLA2R upregulation was not only associated with increased ERK1/2 and cPLA2α phosphorylation but also displayed enhanced apoptosis. In contrast, PLA2R-silenced human podocytes displayed attenuated apoptosis. sPLA2 IB enhanced podocyte arachidonic acid (AA) content in a dose-dependent manner. These data indicate that sPLA2 IB has the potential to induce human podocyte apoptosis via binding to the PLA2R. The sPLA2 IB-PLA2R interaction stimulated podocyte apoptosis through activating ERK1/2 and cPLA2α and through increasing the podocyte AA content.

  20. Secretory and cytosolic phospholipases A2 are activated during TNF priming of human neutrophils.

    PubMed

    Seeds, M C; Jones, D F; Chilton, F H; Bass, D A

    1998-01-23

    Cytokines alter neutrophil (PMN) function during inflammation, and Tumor Necrosis Factor (TNF) in vitro primes PMN such that receptor-mediated stimulation causes markedly enhanced release of arachidonic acid. We hypothesized that two Ca(2+)-dependent PLA2's in PMN might be activated during priming of the cell, thus affecting arachidonate release. A low molecular weight, secretory PLA2 was identified by enzymatic activity in the cell free supernates of primed or stimulated PMN, and in PMN disrupted by nitrogen cavitation. The enzymatic activity was calcium-dependent, acid stable, destroyed by dithiothreitol, and blocked by anti-sPLA2 antibodies. TNF caused secretion of sPLA2 and also caused an increase in cell-associated sPLA2 enzymatic activity. Activation and release were maximal with fMLP stimulation of TNF-primed PMN. Neutrophils also contained a cytosolic PLA2 (cPLA2) characterized by enzymatic activity which was calcium dependent, enhanced by dithiothreitol, and blocked by anti-cPLA2 antibody. TNF caused a doubling of cPLA2 enzymatic activity which was associated with phosphorylation of the enzyme as judged by a migration shift on Western blots. Thus, TNF priming of human PMN caused marked increase in fMLP stimulated AA release in parallel to enhanced activity of two different PLA2's.

  1. A continuous spectrophotometric assay that distinguishes between phospholipase A1 and A2 activities[S

    PubMed Central

    El Alaoui, Meddy; Soulère, Laurent; Noiriel, Alexandre; Popowycz, Florence; Khatib, Abdallah; Queneau, Yves; Abousalham, Abdelkarim

    2016-01-01

    A new spectrophotometric assay was developed to measure, continuously and specifically, phospholipase A1 (PLA1) or phospholipase A2 (PLA2) activities using synthetic glycerophosphatidylcholines (PCs) containing α-eleostearic acid, either at the sn-1 position [1-α-eleostearoyl-2-octadecyl-rac-glycero-3-phosphocholine (EOPC)] or at the sn-2 position [1-octadecyl-2-α-eleostearoyl-rac-glycero-3-phosphocholine (OEPC)]. The substrates were coated onto the wells of microtiter plates. A nonhydrolyzable ether bond, with a non-UV-absorbing alkyl chain, was introduced at the other sn position to prevent acyl chain migration during lipolysis. Upon enzyme action, α-eleostearic acid is liberated and then solubilized into the micellar phase. The PLA1 or PLA2 activity was measured by the increase in absorbance at 272 nm due to the transition of α-eleostearic acid from the adsorbed to the soluble state. EOPC and OEPC differentiate, with excellent accuracy, between PLA1 and PLA2 activity. Lecitase®, guinea pig pancreatic lipase-related protein 2 (known to be a PLA1 enzyme), bee venom PLA2, and porcine pancreatic PLA2 were all used to validate the assay. Compared with current assays used for continuously measuring PLA1 or PLA2 activities and/or their inhibitors, the development of this sensitive enzymatic method, using coated PC substrate analogs to natural lipids and based on the UV spectroscopic properties of α-eleostearic acid, is a significant improvement. PMID:27194811

  2. Stabilization of Resveratrol in Blood Circulation by Conjugation to mPEG and mPEG-PLA Polymers: Investigation of Conjugate Linker and Polymer Composition on Stability, Metabolism, Antioxidant Activity and Pharmacokinetic Profile

    PubMed Central

    Siddalingappa, Basavaraj; Benson, Heather A. E.; Brown, David H.; Batty, Kevin T.; Chen, Yan

    2015-01-01

    Resveratrol is naturally occurring phytochemical with diverse biological activities such as chemoprevention, anti-inflammatory, anti-cancer, anti-oxidant. But undergoes rapid metabolism in the body (half life 0.13h). Hence Polymer conjugation utilizing different chemical linkers and polymer compositions was investigated for enhanced pharmacokinetic profile of resveratrol. Ester conjugates such as α-methoxy-ω-carboxylic acid poly(ethylene glycol) succinylamide resveratrol (MeO-PEGN-Succ-RSV) (2 and 20 kDa); MeO-PEG succinyl ester resveratrol (MeO-PEGO-Succ-RSV) (2 kDa); α-methoxy poly(ethylene glycol)-co-polylactide succinyl ester resveratrol (MeO-PEG-PLAO-Succ-RSV) (2 and 6.6kDa) were prepared by carbodiimide coupling reactions. Resveratrol-PEG ethers (2 and 5 kDa) were synthesized by alkali-mediated etherification. All polymer conjugates were fully characterized in vitro and the pharmacokinetic profile of selected conjugates was characterized in rats. Buffer and plasma stability of conjugates was dependent on polymer hydrophobicity, aggregation behavior and PEG corona, with MeO-PEG-PLAO-Succ-RSV (2 kDa) showing a 3h half-life in rat plasma in vitro. Polymer conjugates irrespective of linker chemistry protected resveratrol against metabolism in vitro. MeO-PEG-PLAO-Succ-RSV (2 kDa), Resveratrol-PEG ether (2 and 5 kDa) displayed improved pharmacokinetic profiles with significantly higher plasma area under curve (AUC), slower clearance and smaller volume of distribution, compared to resveratrol. PMID:25799413

  3. Stabilization of resveratrol in blood circulation by conjugation to mPEG and mPEG-PLA polymers: investigation of conjugate linker and polymer composition on stability, metabolism, antioxidant activity and pharmacokinetic profile.

    PubMed

    Siddalingappa, Basavaraj; Benson, Heather A E; Brown, David H; Batty, Kevin T; Chen, Yan

    2015-01-01

    Resveratrol is naturally occurring phytochemical with diverse biological activities such as chemoprevention, anti-inflammatory, anti-cancer, anti-oxidant. But undergoes rapid metabolism in the body (half life 0.13h). Hence Polymer conjugation utilizing different chemical linkers and polymer compositions was investigated for enhanced pharmacokinetic profile of resveratrol. Ester conjugates such as α-methoxy-ω-carboxylic acid poly(ethylene glycol) succinylamide resveratrol (MeO-PEGN-Succ-RSV) (2 and 20 kDa); MeO-PEG succinyl ester resveratrol (MeO-PEGO-Succ-RSV) (2 kDa); α-methoxy poly(ethylene glycol)-co-polylactide succinyl ester resveratrol (MeO-PEG-PLAO-Succ-RSV) (2 and 6.6kDa) were prepared by carbodiimide coupling reactions. Resveratrol-PEG ethers (2 and 5 kDa) were synthesized by alkali-mediated etherification. All polymer conjugates were fully characterized in vitro and the pharmacokinetic profile of selected conjugates was characterized in rats. Buffer and plasma stability of conjugates was dependent on polymer hydrophobicity, aggregation behavior and PEG corona, with MeO-PEG-PLAO-Succ-RSV (2 kDa) showing a 3h half-life in rat plasma in vitro. Polymer conjugates irrespective of linker chemistry protected resveratrol against metabolism in vitro. MeO-PEG-PLAO-Succ-RSV (2 kDa), Resveratrol-PEG ether (2 and 5 kDa) displayed improved pharmacokinetic profiles with significantly higher plasma area under curve (AUC), slower clearance and smaller volume of distribution, compared to resveratrol.

  4. Silver/poly (lactic acid) nanocomposites: preparation, characterization, and antibacterial activity

    PubMed Central

    Shameli, Kamyar; Ahmad, Mansor Bin; Yunus, Wan Md Zin Wan; Ibrahim, Nor Azowa; Rahman, Russly Abdul; Jokar, Maryam; Darroudi, Majid

    2010-01-01

    In this study, antibacterial characteristic of silver/poly (lactic acid) nanocomposite (Ag/PLA-NC) films was investigated, while silver nanoparticles (Ag-NPs) were synthesized into biodegradable PLA via chemical reduction method in diphase solvent. Silver nitrate and sodium borohydride were respectively used as a silver precursor and reducing agent in the PLA, which acted as a polymeric matrix and stabilizer. Meanwhile, the properties of Ag/PLA-NCs were studied as a function of the Ag-NP weight percentages (8, 16, and 32 wt% respectively), in relation to the use of PLA. The morphology of the Ag/PLA-NC films and the distribution of the Ag-NPs were also characterized. The silver ions released from the Ag/PLA-NC films and their antibacterial activities were scrutinized. The antibacterial activities of the Ag/PLA-NC films were examined against Gram-negative bacteria (Escherichia coli and Vibrio parahaemolyticus) and Gram-positive bacteria (Staphylococcus aureus) by diffusion method using Muller–Hinton agar. The results indicated that Ag/PLA-NC films possessed a strong antibacterial activity with the increase in the percentage of Ag-NPs in the PLA. Thus, Ag/PLA-NC films can be used as an antibacterial scaffold for tissue engineering and medical application. PMID:20856832

  5. Platelet Lipidomic Profiling: Novel Insight into Cytosolic Phospholipase A2α Activity and Its Role in Human Platelet Activation.

    PubMed

    Duvernay, Matthew T; Matafonov, Anton; Lindsley, Craig W; Hamm, Heidi E

    2015-09-15

    With a newer, more selective and efficacious cytosolic phospholipase A2α (cPLA2α) inhibitor available, we revisited the role of cPLAactivity in platelet activation and discovered that a component of platelet signaling, even larger than previously appreciated, relies on this enzyme. In a whole blood shear-based flow chamber assay, giripladib, a cPLA2α inhibitor, reduced platelet adhesion and accumulation on collagen. Moreover, giripladib differentially affected P-selectin expression and GPIIbIIIa activation depending on the agonist employed. While protease-activated receptor 1 (PAR1)-mediated platelet activation was unaffected by giripladib, the levels of PAR4- and GPVI-mediated platelet activation were significantly reduced. Meanwhile, the thromboxane A2 receptor antagonist SQ29548 had no effect on PAR-, GPVI-, or puriniergic receptor-mediated platelet activation, suggesting that another eicosanoid produced downstream of arachidonic acid liberation by cPLA2α was responsible for this large component of PAR4- and GPVI-mediated platelet activation. In parallel, we profiled PAR-mediated changes in glycerophospholipid (GPL) mass with and without giripladib to better understand cPLA2α-mediated lipid metabolism. Phosphatidylcholine and phosphatidylethanolamine (PE) demonstrated the largest consumption of mass during thrombin stimulation. Additionally, we confirm phosphatidylinositol as a major substrate of cPLA2α. A comparison of PAR1- and PAR4-induced metabolism revealed the consumption of more putative arachidonyl-PE species downstream of PAR1 activation. Instead of enhanced cPLAactivity and therefore more arachidonic acid liberation downstream of PAR4, these results indicate the major role that cPLAactivity plays in platelet function and suggest that a novel eicosanoid is produced in response to platelet activation that represents a large component of PAR4- and GPVI-mediated responses.

  6. Platelet Lipidomic Profiling: Novel Insight into Cytosolic Phospholipase A2α Activity and Its Role in Human Platelet Activation.

    PubMed

    Duvernay, Matthew T; Matafonov, Anton; Lindsley, Craig W; Hamm, Heidi E

    2015-09-15

    With a newer, more selective and efficacious cytosolic phospholipase A2α (cPLA2α) inhibitor available, we revisited the role of cPLAactivity in platelet activation and discovered that a component of platelet signaling, even larger than previously appreciated, relies on this enzyme. In a whole blood shear-based flow chamber assay, giripladib, a cPLA2α inhibitor, reduced platelet adhesion and accumulation on collagen. Moreover, giripladib differentially affected P-selectin expression and GPIIbIIIa activation depending on the agonist employed. While protease-activated receptor 1 (PAR1)-mediated platelet activation was unaffected by giripladib, the levels of PAR4- and GPVI-mediated platelet activation were significantly reduced. Meanwhile, the thromboxane A2 receptor antagonist SQ29548 had no effect on PAR-, GPVI-, or puriniergic receptor-mediated platelet activation, suggesting that another eicosanoid produced downstream of arachidonic acid liberation by cPLA2α was responsible for this large component of PAR4- and GPVI-mediated platelet activation. In parallel, we profiled PAR-mediated changes in glycerophospholipid (GPL) mass with and without giripladib to better understand cPLA2α-mediated lipid metabolism. Phosphatidylcholine and phosphatidylethanolamine (PE) demonstrated the largest consumption of mass during thrombin stimulation. Additionally, we confirm phosphatidylinositol as a major substrate of cPLA2α. A comparison of PAR1- and PAR4-induced metabolism revealed the consumption of more putative arachidonyl-PE species downstream of PAR1 activation. Instead of enhanced cPLAactivity and therefore more arachidonic acid liberation downstream of PAR4, these results indicate the major role that cPLAactivity plays in platelet function and suggest that a novel eicosanoid is produced in response to platelet activation that represents a large component of PAR4- and GPVI-mediated responses. PMID:26295742

  7. Active-R filter

    DOEpatents

    Soderstrand, Michael A.

    1976-01-01

    An operational amplifier-type active filter in which the only capacitor in the circuit is the compensating capacitance of the operational amplifiers, the various feedback and coupling elements being essentially solely resistive.

  8. Differential activation of human neutrophil cytosolic phospholipase A2 and secretory phospholipase A2 during priming by 1,2-diacyl- and 1-O-alkyl-2-acylglycerols.

    PubMed

    Seeds, M C; Nixon, A B; Wykle, R L; Bass, D A

    1998-11-01

    We have shown previously that both 1,2-diacylglycerol (AAG) and 1-O-alkyl-2-acylglycerol (EAG) prime neutrophil release of arachidonic acid via uncharacterized phospholipases A2. Therefore, we investigated the actions of EAG and AAG specifically on neutrophil cytosolic (cPLA2) and secretory (sPLA2) phospholipase A2s. We hypothesized that AAG as a protein kinase activator would activate cPLA2 via phosphorylation events. EAG is antagonistic to the AAG activation of PKC, thus it was not expected to act via phosphorylation of cPLA2. Neutrophils were primed with either AAG or EAG and then stimulated with fMLP. When neutrophils were primed with 5-20 microM 1,2-diacylglycerol, a shift was observed in cPLA2 migration on SDS-PAGE gels, consistent with phosphorylation of the protein. This gel shift was not seen after exposure to EAG. AAG also caused a parallel increase in enzymatic activity of cPLA2 that was not seen with EAG. We also investigated whether either diglyceride would cause similar priming or direct secretion of sPLA2. Both AAG and EAG directly caused significant secretion of neutrophil sPLA2. EAG also increased the release of sPLA2 in cells subsequently stimulated with fMLP. Thus, AAG activated cPLA2 and stimulated secretion of sPLA2. In contrast, EAG did not activate cPLA2, but directly activated secretion of sPLA2. We also demonstrated that human synovial fluid sPLA2 increased AA release from resting and fMLP-stimulated neutrophils. Given that diglycerides prime for release of AA, PAF, and LTB4, these current data support the hypothesis that such priming may be mediated by phosphorylation dependent (cPLA2) or phosphorylation independent (e.g. secretion of sPLA2) events.

  9. Cytokine-mediated cPLA(2) phosphorylation is regulated by multiple MAPK family members.

    PubMed

    Geijsen, N; Dijkers, P F; Lammers, J J; Koenderman, L; Coffer, P J

    2000-04-01

    Cytosolic phospholipase A(2) (cPLA(2)) plays a critical role in various neutrophil functions including the generation of leukotrienes and platelet-activating factor release. Enzyme activity is regulated both by translocation to the membrane in a Ca(2+)-dependent manner and serine phosphorylation by members of the mitogen-activated protein kinase (MAPK) family. In this report, we have investigated the role of granulocyte/macrophage colony-stimulating factor (GM-CSF)-mediated signalling pathways in the regulation of cPLA(2). GM-CSF-induced cPLA(2) phosphorylation was not affected by pharmacological inhibition of p38 MAPK, phosphatidylinositol 3-kinase or Src. However, inhibition of extracellular signal-regulated kinase (ERK) MAPK activation resulted in a partial inhibition of cPLA(2) phosphorylation, revealed in a slower onset of phosphorylation. A cell line stably transfected with the GM-CSF receptor was used to further analyze GM-CSF-mediated cPLA(2) phosphorylation. Mutation of tyrosine residues 577 and 612 resulted in a delayed cPLA(2) phosphorylation similar to the pharmacological ERK inhibition. Furthermore, inhibition of p38 MAPK in cells bearing the double mutant betac577/612 completely abrogated GM-CSF-induced cPLA(2) phosphorylation. We conclude that GM-CSF can mediate cPLA(2) phosphorylation through the redundant activation of both p38 and ERK MAP kinases.

  10. Phospholipase A2-like activity of human bocavirus VP1 unique region.

    PubMed

    Qu, Xiao-Wang; Liu, Wen-Pei; Qi, Zheng-Yu; Duan, Zhao-Jun; Zheng, Li-Shu; Kuang, Zi-Zhou; Zhang, Wan-Ju; Hou, Yun-De

    2008-01-01

    Human bocavirus (HBoV) is a new parvovirus first discovered in 2005, which is associated with acute respiratory infection. Analysis of sequence homology has revealed that a putative phospholipase A2 (PLA2) motif exists in the VP1 unique region of HBoV. However, little is known about whether the VP1 unique region of HBoV has PLA2 enzymatic activity and how these critical residues contribute to its PLA2 activity. To address these issues, the VP1 unique region protein and four of its mutants, were expressed in Eschericha coli. The purified VP1 unique protein (VP1U) showed a typical Ca2+-dependent secreted PLA2-like (sPLA2) activity, which was inhibited by sPLA2-specific inhibitors in a time-dependent manner. Mutation of one of the amino acids (21Pro, 41His, 42Asp or 63Asp) in VP1U almost eliminated the sPLA2 activity of HBoV VP1U. These data indicate that VP1U of HBoV has sPLA2-like enzymatic activity, and these residues are crucial for its sPLA2-like activity. Potentially, VP1U may be a target for the development of anti-viral drugs for HBoV.

  11. Cross-reactivity of anti-PLA2R1 autoantibodies to rabbit and mouse PLA2R1 antigens and development of two novel ELISAs with different diagnostic performances in idiopathic membranous nephropathy.

    PubMed

    Seitz-Polski, Barbara; Dolla, Guillaume; Payré, Christine; Tomas, Nicola M; Lochouarn, Marine; Jeammet, Louise; Mariat, Christophe; Krummel, Thierry; Burtey, Stéphane; Courivaud, Cécile; Schlumberger, Wolfgang; Zorzi, Kévin; Benzaken, Sylvia; Bernard, Ghislaine; Esnault, Vincent L M; Lambeau, Gérard

    2015-11-01

    About 70% of patients with idiopathic membranous nephropathy (iMN) have autoantibodies to the phospholipase A2 receptor PLA2R1. We screened sera from iMN patients for their cross-reactivity to human (h), rabbit (rb) and mouse (m) PLA2R1 by western blot (WB) and antigen-specific ELISAs. All iMN patients recognized hPLA2R1 and rbPLA2R1 by WB, and a rbPLA2R1 ELISA was as sensitive as the standardized hPLA2R1 ELISA to monitor anti-PLA2R1 in patients with active disease or in drug-induced remission. In contrast, only 51% of patients were reactive to mPLA2R1 by WB, and a maximum of 78% were weakly to highly positive in the mPLA2R1 ELISA, suggesting that iMN patients exhibit different subsets of anti-PLA2R1 autoantibodies against epitopes that are shared or not among PLA2R1 orthologs. In a cohort of 41 patients with a mean follow-up of 42 months from anti-PLA2R1 assay, the detection of anti-mPLA2R1 autoantibodies was an independent predictor of clinical outcome in multivariate analysis (p = 0.009), and a ROC curve analysis identified a threshold of 605 RU/mL above which 100% of patients (12 patients) had a poor renal outcome (p < 0.001). A similar threshold could not be defined in hPLA2R1 and rbPLA2R1 ELISAs. We conclude that rbPLA2R1 is an alternative antigen to hPLA2R1 to measure anti-PLA2R1 in active disease while mPLA2R1 is a unique antigen that can detect a subset of anti-PLA2R1 autoantibodies present at high levels (>605 RU/mL) only in iMN patients at risk of poor prognosis, and is thus useful to predict iMN outcome. PMID:26296473

  12. Research Maps New Routes for Reading Success in PLA Early Childhood Initiative.

    ERIC Educational Resources Information Center

    Meyers, Elaine

    2002-01-01

    The Public Library Association (PLA) partnered with the National Institute of Child Health and Human Development (NICHD) to develop research-based tools for parents to prepare children for reading. Inherent in the materials is the major role of the public library in formation of readers. Outlines goals and activities (2001-2002) of the PLA/ALSC…

  13. sPLA2 and the epidermal barrier

    PubMed Central

    Ilic, Dusko; Bollinger, James M.; Gelb, Michael; Mauro, Theodora M.

    2015-01-01

    The mammalian epidermis provides both an interface and a protective barrier between the organism and its environment. Lipid, processed into water-impermeable bilayers between the outermost layers of the epidermal cells, forms the major barrier that prevents water from exiting the organism, and also prevents toxins and infectious agents from entering. The secretory phospholipase 2 (sPLA2) enzymes control important processes in skin and other organs, including inflammation and differentiation. sPLA2 activity contributes to epidermal barrier formation and homeostasis by generating free fatty acids, which are required both for formation of lamellar membranes and also for acidification of the stratum corneum (SC). sPLA2 is especially important in controlling SC acidification and establishment of an optimum epidermal barrier during the first postnatal week. Several sPLA2 isoforms are present in the epidermis. We find that two of these isoforms, sPLA2 IIA and sPLA2 IIF, localize to the upper stratum granulosum and increase in response to experimental barrier perturbation. sPLA2F−/− mice also demonstrate a more neutral SC pH than do their normal littermates, and their initial recovery from barrier perturbation is delayed. These findings confirm that sPLA2 enzymes perform important roles in epidermal development, and suggest that the sPLA2IIF isoform may be central to SC acidification and barrier function. This article is part of a Special Issue entitled The Important Role of Lipids in the Epidermis and their Role in the Formation and Maintenance of the Cutaneous Barrier. Guest Editors: Kenneth R. Feingold and Peter Elias. PMID:24269828

  14. Redox-active antioxidant modulation of lipid signaling in vascular endothelial cells: vitamin C induces activation of phospholipase D through phospholipase A2, lipoxygenase, and cyclooxygenase

    PubMed Central

    Steinhour, Emily; Sherwani, Shariq I.; Mazerik, Jessica N.; Ciapala, Valorie; Butler, Elizabeth O’Connor; Cruff, Jason P.; Magalang, Ulysses; Parthasarathy, Sampath; Sen, Chandan K.; Marsh, Clay B.; Kuppusamy, Periannan

    2015-01-01

    We have earlier reported that the redox-active antioxidant, vitamin C (ascorbic acid), activates the lipid signaling enzyme, phospholipase D (PLD), at pharmacological doses (mM) in the bovine lung microvascular endothelial cells (BLMVECs). However, the activation of phospholipase A2 (PLA2), another signaling phospholipase, and the modulation of PLD activation by PLA2 in the ECs treated with vitamin C at pharmacological doses have not been reported to date. Therefore, this study aimed at the regulation of PLD activation by PLA2 in the cultured BLMVECs exposed to vitamin C at pharmacological concentrations. The results revealed that vitamin C (3–10 mM) significantly activated PLA2 starting at 30 min; however, the activation of PLD resulted only at 120 min of treatment of cells under identical conditions. Further studies were conducted utilizing specific pharmacological agents to understand the mechanism(s) of activation of PLA2 and PLD in BLMVECs treated with vitamin C (5 mM) for 120 min. Antioxidants, calcium chelators, iron chelators, and PLA2 inhibitors offered attenuation of the vitamin C-induced activation of both PLA2 and PLD in the cells. Vitamin C was also observed to significantly induce the formation and release of the cyclooxygenase (COX)- and lipoxygenase (LOX)-catalyzed arachidonic acid (AA) metabolites and to activate the AA LOX in BLMVECs. The inhibitors of PLA2, COX, and LOX were observed to effectively and significantly attenuate the vitamin C-induced PLD activation in BLMVECs. For the first time, the results of the present study revealed that the vitamin C-induced activation of PLD in vascular ECs was regulated by the upstream activation of PLA2, COX, and LOX through the formation of AA metabolites involving oxidative stress, calcium, and iron. PMID:18496733

  15. Phospholipase PlaB of Legionella pneumophila Represents a Novel Lipase Family

    PubMed Central

    Bender, Jennifer; Rydzewski, Kerstin; Broich, Markus; Schunder, Eva; Heuner, Klaus; Flieger, Antje

    2009-01-01

    Legionella pneumophila possesses several phospholipases capable of host cell manipulation and lung damage. Recently, we discovered that the major cell-associated hemolytic phospholipase A (PlaB) shares no homology to described phospholipases and is dispensable for intracellular replication in vitro. Nevertheless, here we show that PlaB is the major lipolytic activity in L. pneumophila cell infections and that PlaB utilizes a typical catalytic triad of Ser-Asp-His for effective hydrolysis of phospholipid substrates. Crucial residues were found to be located within the N-terminal half of the protein, and amino acids embedding these active sites were unique for PlaB and homologs. We further showed that catalytic activity toward phosphatidylcholine but not phosphatidylglycerol is directly linked to hemolytic potential of PlaB. Although the function of the prolonged PlaB C terminus remains to be elucidated, it is essential for lipolysis, since the removal of 15 amino acids already abolishes enzyme activity. Additionally, we determined that PlaB preferentially hydrolyzes long-chain fatty acid substrates containing 12 or more carbon atoms. Since phospholipases play an important role as bacterial virulence factors, we examined cell-associated enzymatic activities among L. pneumophila clinical isolates and non-pneumophila species. All tested clinical isolates showed comparable activities, whereas of the non-pneumophila species, only Legionella gormanii and Legionella spiritensis possessed lipolytic activities similar to those of L. pneumophila and comprised plaB-like genes. Interestingly, phosphatidylcholine-specific phospholipase A activity and hemolytic potential were more pronounced in L. pneumophila. Therefore, hydrolysis of the eukaryotic membrane constituent phosphatidylcholine triggered by PlaB could be an important virulence tool for Legionella pathogenicity. PMID:19640837

  16. Repression of PLA2R1 by c-MYC and HIF-2alpha promotes cancer growth

    PubMed Central

    Vindrieux, David; Devailly, Guillaume; Augert, Arnaud; Calvé, Benjamin Le; Ferrand, Mylène; Pigny, Pascal; Payen, Léa; Lambeau, Gérard; Perrais, Michael; Aubert, Sébastien; Simonnet, Hélène; Dante, Robert; Bernard, David

    2014-01-01

    Loss of secreted phospholipase A2 receptor (PLA2R1) has recently been found to render human primary cells more resistant to senescence whereas increased PLA2R1 expression is able to induce cell cycle arrest, cancer cell death or blockage of cancer cell transformation in vitro, suggesting that PLA2R1 displays tumor suppressive activities. Here we report that PLA2R1 expression strongly decreases in samples of human renal cell carcinoma (RCC). Knockdown of PLA2R1 increases renal cancer cell tumorigenicity supporting a role of PLA2R1 loss to promote in vivo RCC growth. Most RCC result from Von Hippel-Lindau (VHL) tumor suppressor loss-of-function and subsequent gain-of-function of the oncogenic HIF-2alpha/c-MYC pathway. Here, by genetically manipulating VHL, HIF-2alpha and c-MYC, we demonstrate that loss of VHL, stabilization of HIF-2alpha and subsequent increased c-MYC activity, binding and transcriptional repression, through induction of PLA2R1 DNA methylation closed to PLA2R1 transcriptional start site, results in decreased PLA2R1 transcription. Our results describe for the first time an oncogenic pathway leading to PLA2R1 transcriptional repression and the importance of this repression for tumor growth. PMID:24657971

  17. Structure and blood compatibility of highly oriented PLA/MWNTs composites produced by solid hot drawing.

    PubMed

    Li, Zhengqiu; Zhao, Xiaowen; Ye, Lin; Coates, Phil; Caton-Rose, Fin; Martyn, Michasel

    2014-03-01

    Highly oriented poly(lactic acid) (PLA)/multi-walled carbon nanotubes (MWNTs) composites were fabricated through solid hot drawing technology in an effort to improve the mechanical properties and blood biocompatibility of PLA as blood-contacting medical devices. It was found that proper MWNTs content and drawing orientation can improve the tensile strength and modulus of PLA dramatically. With the increase in draw ratio, the cold crystallization peak became smaller, and the glass transition and the melting peak of PLA moved to high temperature, while the crystallinity increased, and the grain size decreased, indicating the stress-induced crystallization of PLA during drawing. MWNTs showed a nucleation effect on PLA, leading to the rise in the melting temperature, increase in crystallinity and reduction of spherulite size for the composites. Moreover, the intensity of (002) diffraction of MWNTs increased with draw ratio, indicating that MWNTs were preferentially aligned and oriented during drawing. Microstructure observation demonstrated that PLA matrix had an ordered fibrillar bundle structure, and MWNTs in the composite tended to align parallel to the drawing direction. In addition, the dispersion of MWNTs in PLA was also improved by orientation. Introduction of MWNTs and drawing orientation could significantly enhance the blood compatibility of PLA by prolonging kinetic clotting time, reducing hemolysis ratio and platelet activation.

  18. Inactivation of Peroxiredoxin 6 by the Pla Protease of Yersinia pestis.

    PubMed

    Zimbler, Daniel L; Eddy, Justin L; Schroeder, Jay A; Lathem, Wyndham W

    2015-11-09

    Pneumonic plague represents the most severe form of disease caused by Yersinia pestis due to its ease of transmission, rapid progression, and high mortality rate. The Y. pestis outer membrane Pla protease is essential for the development of pneumonic plague; however, the complete repertoire of substrates cleaved by Pla in the lungs is not known. In this study, we describe a proteomic screen to identify host proteins contained within the bronchoalveolar lavage fluid of mice that are cleaved and/or processed by Y. pestis in a Pla-dependent manner. We identified peroxiredoxin 6 (Prdx6), a host factor that contributes to pulmonary surfactant metabolism and lung defense against oxidative stress, as a previously unknown substrate of Pla. Pla cleaves Prdx6 at three distinct sites, and these cleavages disrupt both the peroxidase and phospholipase A2 activities of Prdx6. In addition, we found that infection with wild-type Y. pestis reduces the abundance of extracellular Prdx6 in the lungs compared to that after infection with Δpla Y. pestis, suggesting that Pla cleaves Prdx6 in the pulmonary compartment. However, following infection with either wild-type or Δpla Y. pestis, Prdx6-deficient mice exhibit no differences in bacterial burden, host immune response, or lung damage from wild-type mice. Thus, while Pla is able to disrupt Prdx6 function in vitro and reduce Prdx6 levels in vivo, the cleavage of Prdx6 has little detectable impact on the progression or outcome of pneumonic plague.

  19. Trichomonas vaginalis: identification of soluble and membrane-associated phospholipase A1 and A2 activities with direct and indirect hemolytic effects.

    PubMed

    Vargas-Villarreal, Javier; Mata-Cárdenas, Benito David; Palacios-Corona, Rebeca; González-Salazar, Francisco; Cortes-Gutierrez, Elva I; Martínez-Rodríguez, Herminia G; Said-Fernández, Salvador

    2005-02-01

    A direct hemolytic activity, dependent on phospholipase A (PLA) activity, was located in the particulate subcellular fraction (P30) of Trichomonas vaginalis. We identified soluble direct and indirect hemolytic activities in the spent medium and soluble fraction (S30) of T. vaginalis strain GT-13. Spent medium showed the highest specific indirect hemolytic activity (SIHA) at pH 6.0 (91 indirect hemolytic units [HU]/mg/hr). Spent medium and P30, but not S30, showed direct hemolytic activity. PLA activity was protein dose dependent and time dependent. The highest PLA activity was observed at pH 6.0. All trichomonad preparations showed phospholipase A1 (PLA A1) and phospholipase A2 (PLA A2) activities. Indirect and direct hemolytic activity and PLA A1 and PLA A2 diminished at pH 6.0 and 8.0 with increasing concentrations of Rosenthal's inhibitor. The greatest effect was observed with 80 microM at pH 6.0 on the SIHA of S30 (83% reduction) and the lowest at pH 8.0, also on the SIHA of S30 (26% reduction). In conclusion, T. vaginalis contains particulate and soluble acidic, and alkaline direct and indirect hemolytic activities, which are partially dependent on alkaline or acidic PLA A1 and PLA A2 enzymes. These could be responsible for the contact-dependent and -independent hemolytic and cytolytic activities of T. vaginalis. PMID:15856864

  20. Characteristics and cytotoxicity of folate-modified curcumin-loaded PLA-PEG micellar nano systems with various PLA:PEG ratios.

    PubMed

    Phan, Quoc Thong; Le, Mai Huong; Le, Thi Thu Huong; Tran, Thi Hong Ha; Xuan, Phuc Nguyen; Ha, Phuong Thu

    2016-06-30

    Targeting delivery system use natural drugs for tumor cells is an appealing platform help to reduce the side effects and enhance the therapeutic effects of the drug. In this study, we synthesized curcumin (Cur) loaded (D, L Poly lactic - Poly ethylenglycol) micelle (Cur/PLA-PEG) with the ratio of PLA/PEG of 3:1 2:1 1:1 1:2 and 1:3 (w/w) and another micelle modified by folate (Cur/PLA-PEG-Fol) for targeting cancer therapy. The PLA-PEG copolymer was synthesized by ring opening polymerization method. After loading onto the micelle, solubility of Cur increased from 0.38 to 0.73mgml(-1). The average size of prepared Cur/PLA-PEG micelles was from 60 to 69nm (corresponding to the ratio difference of PLA/PEG) and the drug encapsulating efficiency was from 48.8 to 91.3%. Compared with the Cur/PLA-PEG micelles, the size of Cur/PLA-PEG-Fol micelles were from 80 to 86nm and showed better in vitro cellular uptake and cytotoxicity towards HepG2 cells. The cytotoxicity of the NPs however depends much on the PEG component. The results demonstrated that Folate-modified micelles could serve as a potential nano carrier to improve solubility, anti-cancer activity of Cur and targeting ability of the system.

  1. Complete regression of xenograft tumors using biodegradable mPEG-PLA-SN38 block copolymer micelles.

    PubMed

    Lu, Lu; Zheng, Yan; Weng, Shuqiang; Zhu, Wenwei; Chen, Jinhong; Zhang, Xiaomin; Lee, Robert J; Yu, Bo; Jia, Huliang; Qin, Lunxiu

    2016-06-01

    7-Ethyl-10-hydroxy-comptothecin (SN38) is an active metabolite of irinotecan (CPT-11) and the clinical application of SN38 is limited by its hydrophobicity and instability. To address these issues, a series of novel amphiphilic mPEG-PLA-SN38-conjugates were synthesized by linking SN38 to mPEG-PLA-SA, and they could form micelles by self-assembly. The effects of mPEG-PLA composition were studied in vitro and in vivo. The mean diameters of mPEG2K-PLA-SN38 micelles and mPEG4K-PLA-SN38 micelles were 10-20nm and 120nm, respectively, and mPEG2K-PLA-SN38 micelles showed greater antitumor efficacy than mPEG4K-PLA-SN38 micelles both in vitro and in vivo. These data suggest that the lengths of mPEG and PLA chains had a major impact on the physicochemical characteristics and antitumor activity of SN38-conjugate micelles.

  2. Persistence of high intestinal lactase activity in Pakistan.

    PubMed

    Abbas, H; Ahmad, M

    1983-01-01

    In order to determine the incidence of persistence of high intestinal lactase activity (PLA) in a Pakistani human population, 53 probands belonging to the Punjabi ethnic group were examined using a lactose tolerance test. The incidence of PLA in the sample was found to be 55%, which has been compared with the incidence in other ethnic groups racially or geographically related to the Pakistani population. Various possible explanations for the fairly high incidence of PLA in the Punjabi ethnic group have been discussed. PMID:6885071

  3. Platelet phospholipase A(2) activity in Alzheimer's disease and mild cognitive impairment.

    PubMed

    Gattaz, W F; Forlenza, O V; Talib, L L; Barbosa, N R; Bottino, C M C

    2004-05-01

    Phospholipase A(2) (PLA(2)) controls the metabolism of phospholipids in cell membranes. In the brain, PLA(2) influences the processing of the amyloid precursor protein (APP) and thus the production of the amyloid-beta peptides (Abeta), which are the major components of the senile plaques in Alzheimer's disease (AD). Reduced PLA(2) activity has been reported in brain and in platelets of AD patients. In the present study we investigated PLA(2) activity in platelets from 21 AD patients as compared to 17 healthy elderly controls and 11 individuals with mild cognitive impairment (MCI). Subjects were cognitively assessed by the Mini-Mental State Examination (MMSE) and the CAMDEX schedule. Platelet PLA(2) activity was determined by radio-enzymatic assay, which mainly detected a calcium-independent form of the enzyme present also in the brain (iPLA(2)). PLA(2) activity was significantly lower in AD than in controls (p < 0.001). Mean PLA(2) activity in MCI individuals was between the values of AD patients and controls, with a subgroup showing PLA as low as the lowest AD patients, but the differences from MCI were not significant from AD and control groups. Lower PLA(2) activity was significantly correlated with a worse cognitive performance both at the MMSE (p = 0.001) and the cognitive sub-scale of the CAMDEX inventory (p = 0.002). Our data replicate previous findings of reduced platelet PLA(2) activity in AD. Both reduced PLA(2) activity and the correlation with impaired cognition were also reported in brain tissue of AD patients, suggesting thus that the present determinations in platelets may be related to a reduction in the brain. In the brain the inhibition of PLA(2) inhibits the physiological secretion of the APP, a mechanism that increases Abeta formation. Further longitudinal studies should investigate whether those MCI individuals with the lowest PLA(2) values in platelets would be at a higher risk to develop AD during a longitudinal follow up. PMID:15088152

  4. Lithium activates brain phospholipase A2 and improves memory in rats: implications for Alzheimer's disease.

    PubMed

    Mury, Fábio B; da Silva, Weber C; Barbosa, Nádia R; Mendes, Camila T; Bonini, Juliana S; Sarkis, Jorge Eduardo Souza; Cammarota, Martin; Izquierdo, Ivan; Gattaz, Wagner F; Dias-Neto, Emmanuel

    2016-10-01

    Phospholipase A2 (Pla2) is required for memory retrieval, and its inhibition in the hippocampus has been reported to impair memory acquisition in rats. Moreover, cognitive decline and memory deficits showed to be reduced in animal models after lithium treatment, prompting us to evaluate possible links between Pla2, lithium and memory. Here, we evaluated the possible modulation of Pla2 activity by a long-term treatment of rats with low doses of lithium and its impact in memory. Wistar rats were trained for the inhibitory avoidance task, treated with lithium for 100 days and tested for perdurability of long-term memory. Hippocampal samples were used for quantifying the expression of 19 brain-expressed Pla2 genes and for evaluating the enzymatic activity of Pla2 using group-specific radio-enzymatic assays. Our data pointed to a significant perdurability of long-term memory, which correlated with increased transcriptional and enzymatic activities of certain members of the Pla2 family (iPla2 and sPla2) after the chronic lithium treatment. Our data suggest new possible targets of lithium, add more information on its pharmacological activity and reinforce the possible use of low doses of lithium for the treatment of neurodegenerative conditions such as the Alzheimer's disease. PMID:26661385

  5. Lithium activates brain phospholipase A2 and improves memory in rats: implications for Alzheimer's disease.

    PubMed

    Mury, Fábio B; da Silva, Weber C; Barbosa, Nádia R; Mendes, Camila T; Bonini, Juliana S; Sarkis, Jorge Eduardo Souza; Cammarota, Martin; Izquierdo, Ivan; Gattaz, Wagner F; Dias-Neto, Emmanuel

    2016-10-01

    Phospholipase A2 (Pla2) is required for memory retrieval, and its inhibition in the hippocampus has been reported to impair memory acquisition in rats. Moreover, cognitive decline and memory deficits showed to be reduced in animal models after lithium treatment, prompting us to evaluate possible links between Pla2, lithium and memory. Here, we evaluated the possible modulation of Pla2 activity by a long-term treatment of rats with low doses of lithium and its impact in memory. Wistar rats were trained for the inhibitory avoidance task, treated with lithium for 100 days and tested for perdurability of long-term memory. Hippocampal samples were used for quantifying the expression of 19 brain-expressed Pla2 genes and for evaluating the enzymatic activity of Pla2 using group-specific radio-enzymatic assays. Our data pointed to a significant perdurability of long-term memory, which correlated with increased transcriptional and enzymatic activities of certain members of the Pla2 family (iPla2 and sPla2) after the chronic lithium treatment. Our data suggest new possible targets of lithium, add more information on its pharmacological activity and reinforce the possible use of low doses of lithium for the treatment of neurodegenerative conditions such as the Alzheimer's disease.

  6. Antibacterial electrospun poly(lactic acid) (PLA) nanofibrous webs incorporating triclosan/cyclodextrin inclusion complexes.

    PubMed

    Kayaci, Fatma; Umu, Ozgun C O; Tekinay, Turgay; Uyar, Tamer

    2013-04-24

    Solid triclosan/cyclodextrin inclusion complexes (TR/CD-IC) were obtained and then incorporated in poly(lactic acid) (PLA) nanofibers via electrospinning. α-CD, β-CD, and γ-CD were tested for the formation of TR/CD-IC by a coprecipitation method; however, the findings indicated that α-CD could not form an inclusion complex with TR, whereas β-CD and γ-CD successfully formed TR/CD-IC crystals, and the molar ratio of TR to CD was found to be 1:1. The structural and thermal characteristics of TR/CD-IC were investigated by (1)H NMR, FTIR, XRD, DSC, and TGA studies. Then, the encapsulation of TR/β-CD-IC and TR/γ-CD-IC in PLA nanofibers was achieved. Electrospun PLA and PLA/TR nanofibers obtained for comparison were uniform, whereas the aggregates of TR/CD-IC crystals were present and distributed within the PLA fiber matrix as confirmed by SEM and XRD analyses. The antibacterial activity of these nanofibrous webs was investigated. The results indicated that PLA nanofibers incorporating TR/CD-IC showed better antibacterial activity against Staphylococcus aureus and Escherichia coli bacteria compared to PLA nanofibers containing only TR without CD-IC. Electrospun nanofibrous webs incorporating TR/CD-IC may be applicable in active food packaging due to their very high surface area and nanoporous structure as well as efficient antibacterial property.

  7. Active turbulence in active nematics

    NASA Astrophysics Data System (ADS)

    Thampi, S. P.; Yeomans, J. M.

    2016-07-01

    Dense, active systems show active turbulence, a state characterised by flow fields that are chaotic, with continually changing velocity jets and swirls. Here we review our current understanding of active turbulence. The development is primarily based on the theory and simulations of active liquid crystals, but with accompanying summaries of related literature.

  8. Antisnake venom activity of ethanolic seed extract of Strychnos nux vomica Linn.

    PubMed

    Chatterjee, Ipshita; Chakravarty, A K; Gomes, A

    2004-05-01

    The whole seed extract of S. nux vomica (in low doses) effectively neutralized Daboia russelii venom induced lethal, haemorrhage, defibrinogenating, PLA2 enzyme activity and Naja kaouthia venom induced lethal, cardiotoxic, neurotoxic, PLA2 enzyme activity. The seed extract potentiated polyvalent snake venom antiserum action in experimental animals. An active compound (SNVNF) was isolated and purified by thin layer chromatography and silica gel column chromatography, which effectively antagonised D. russelii venom induced lethal, haemorrhagic, defibrinogenating, oedema, PLA2 enzyme activity and N. kaouthia induced lethal, cardiotoxic, neurotoxic, PLA, enzyme activity. Polyvalent snake venom antiserum action was significantly potentiated by the active compound. Spectral studies revealed it to be a small, straight chain compound containing methyl and amide radicals. Detailed structure elucidation of the compound (SNVNF) is warranted before its clinical trials as a snake venom antagonist.

  9. Effect of chlorogenic acid (5-Caffeoylquinic Acid) isolated from Baccharis oxyodonta on the structure and pharmacological activities of secretory phospholipase A2 from Crotalus durissus terrificus.

    PubMed

    Toyama, Daniela O; Ferreira, Marcelo J P; Romoff, Paulete; Fávero, Oriana A; Gaeta, Henrique H; Toyama, Marcos H

    2014-01-01

    The aim of this paper was to investigate the effect of chlorogenic acid (5-caffeoylquinic acid, 5CQA), isolated from Baccharis oxyodonta, on the structure and pharmacological effect of secretory phospholipase A2 (sPLA2) from Crotalus durissus terrificus. All in vitro and in vivo experiments were conducted using a purified sPLA2 compared under the same experimental conditions with sPLA2 : 5CQA. 5CQA induced several discrete modifications in the secondary structure and the hydrophobic characteristics of native sPLA2 that induced slight changes in the α-helical content, increase in the random coil structure, and decrease of fluorescence of native sPLA2. Moreover, 5CQA significantly decreased the enzymatic activity and the oedema and myonecrosis induced by native sPLA2. As the catalytic activity of sPLA2 plays an important role in several of its biological and pharmacological properties, antibacterial activity was used to confirm the decrease in its enzymatic activity by 5CQA, which induced massive bacterial cell destruction. We found that 5CQA specifically abolished the enzymatic activity of sPLA2 and induced discrete protein unfolding that mainly involved the pharmacological site of sPLA2. These results showed the potential application of 5CQA in the snake poisoning treatment and modulation of the pathological effect of inflammation induced by secretory PLA2.

  10. Effect of Chlorogenic Acid (5-Caffeoylquinic Acid) Isolated from Baccharis oxyodonta on the Structure and Pharmacological Activities of Secretory Phospholipase A2 from Crotalus durissus terrificus

    PubMed Central

    Toyama, Daniela O.; Ferreira, Marcelo J. P.; Romoff, Paulete; Fávero, Oriana A.; Gaeta, Henrique H.; Toyama, Marcos H.

    2014-01-01

    The aim of this paper was to investigate the effect of chlorogenic acid (5-caffeoylquinic acid, 5CQA), isolated from Baccharis oxyodonta, on the structure and pharmacological effect of secretory phospholipase A2 (sPLA2) from Crotalus durissus terrificus. All in vitro and in vivo experiments were conducted using a purified sPLA2 compared under the same experimental conditions with sPLA2 : 5CQA. 5CQA induced several discrete modifications in the secondary structure and the hydrophobic characteristics of native sPLA2 that induced slight changes in the α-helical content, increase in the random coil structure, and decrease of fluorescence of native sPLA2. Moreover, 5CQA significantly decreased the enzymatic activity and the oedema and myonecrosis induced by native sPLA2. As the catalytic activity of sPLA2 plays an important role in several of its biological and pharmacological properties, antibacterial activity was used to confirm the decrease in its enzymatic activity by 5CQA, which induced massive bacterial cell destruction. We found that 5CQA specifically abolished the enzymatic activity of sPLA2 and induced discrete protein unfolding that mainly involved the pharmacological site of sPLA2. These results showed the potential application of 5CQA in the snake poisoning treatment and modulation of the pathological effect of inflammation induced by secretory PLA2. PMID:25258715

  11. Fabrication of nanofibrous scaffold using a PLA and hagfish thread keratin composite; its effect on cell adherence, growth, and osteoblast differentiation.

    PubMed

    Kim, Beom-Su; Park, Ko Eun; Park, Won Ho; Lee, Jun

    2013-08-01

    Electrospinning is a useful method for the production of nanofibrous scaffolds in the field of tissue engineering. Keratin has been used as a biomaterial for electrospinning and can be used in a variety of biomedical applications because it is a natural protein, giving it the ability to improve cell affinity of scaffolds. In this study, keratin was extracted from hagfish slime thread (H-keratin) and blended with polylactic acid (PLA) polymer solution to construct a nanofibrous scaffold. Wool keratin (W-keratin) was used as a control for the comparison of morphological, physical, and biological properties. The results of Fourier transform infrared spectroscopy showed the presence of both W-keratin and H-keratin in the electrospun PLA/keratin. Observations with a scanning electron microscope revealed that PLA, PLA/W-keratin, and PLA/H-keratin had similar average diameters (~800 nm). Cell attachment experiments showed that MG-63 cells adhered more rapidly and spread better onto PLA/H-keratin than onto the pure PLA or PLA/W-keratin. Cell proliferation assay, DNA content, live/dead, and alkaline phosphatase activity assays showed that PLA/H-keratin scaffolds could accelerate the viability, proliferation, and osteogenesis of MG-63 cells relative to pure PLA or PLA/W-keratin nanofibrous scaffolds. These findings suggest that H-keratin can improve cellular attraction and has great potential to be used as a biomaterial in bone tissue engineering.

  12. Activity Scale.

    ERIC Educational Resources Information Center

    Kerpelman, Larry C.; Weiner, Michael J.

    This twenty-four item scale assesses students' actual and desired political-social activism in terms of physical participation, communication activities, and information-gathering activities. About ten minutes are required to complete the instrument. The scale is divided into two subscales. The first twelve items (ACT-A) question respondents on…

  13. Proteasome Activators

    PubMed Central

    Stadtmueller, Beth M.; Hill, Christopher P.

    2011-01-01

    Summary Proteasomes degrade a multitude of protein substrates in the cytosol and nucleus, and thereby are essential for many aspects of cellular function. Because the proteolytic sites are sequestered in a closed barrel-shaped structure, activators are required to facilitate substrate access. Structural and biochemical studies of two activator families, 11S and Blm10, have provided insights to proteasome activation mechanisms, although the biological functions of these factors remain obscure. Recent advances have improved our understanding of the third activator family, including the 19S activator, which targets polyubiquitylated proteins for degradation. PMID:21211719

  14. Cognitive Stimulation Modulates Platelet Total Phospholipases A2 Activity in Subjects with Mild Cognitive Impairment

    PubMed Central

    Balietti, Marta; Giuli, Cinzia; Fattoretti, Patrizia; Fabbietti, Paolo; Postacchini, Demetrio; Conti, Fiorenzo

    2016-01-01

    We evaluated the effect of cognitive stimulation (CS) on platelet total phospholipases A2 activity (tPLA2A) in patients with mild cognitive impairment (MCI_P). At baseline, tPLA2A negatively correlated with Mini-Mental State Examination score (MMSE_s): patients with MMSE_s <26 (Subgroup 1) had significantly higher activity than those with MMSE_s ≥26 (Subgroup 2), who had values similar to the healthy elderly. Regarding CS effect, Subgroup 1 had a significant tPLA2A reduction, whereas Subgroup 2 did not significantly changes after training. Our results showed for the first time that tPLA2A correlates with the cognitive conditions of MCI_P, and that CS acts selectively on subjects with a dysregulated tPLA2A. PMID:26836161

  15. [Anti-NEP and anti-PLA2R antibodies in membranous nephropathy: an update].

    PubMed

    Pozdzik, A A; Debiec, H; I Brochériou; Husson, C; Rorive, S; Broeders, N; Le Moine, A; Ronco, P; Nortier, J

    2015-01-01

    Membranous nephropathy (MN) is the most common cause for nephrotic syndrome in adults and occurs as an idiopathic (primary) or secondary disease. Since the early 2000's, substantial advances have been made in the understanding of the molecular bases of MN. The neutral endopeptidase (NEP) and the receptor for secretory phospholipase A2 (PLA2R) have been identified as target antigens for circulating and deposited antibodies in allo-immune neonatal and adult " idiopathic " MN, respectively. These antibodies recognize specific antigens of podocytes, precipitate as subepithelial immune complexes and activate complement leading to proteinuria. Anti-PLA2R antibodies are of particular clinical importance. Indeed, they are detected in approximately 70% of primary MN in adults, demonstrating that MN actually is an autoimmune condition specific to the kidney. In Europeans, genome-wide studies have shown an association between alleles of PLA2R1 and HLA DQA1 (class II genes of tissue histocompatibility complex) genes and idiopathic MN. Newly developed diagnostic tests detecting circulating anti-PLA2R antibody and PLA2R antigen in glomerular deposits have induced a change in paradigm in the diagnostic approach of idiopathic MN. Measurement of circulating anti-PLA2R antibody is also very useful for the monitoring of MN activity. However, the mechanisms responsible for the formation of anti-PLA2R antibodies as well as those involved in the progression of MN to end-stage renal disease remain to be defined.

  16. Effect of neuroleptics on phospholipase A2 activity in the brain of rats.

    PubMed

    Trzeciak, H I; Kalaciński, W; Małecki, A; Kokot, D

    1995-01-01

    The effect of neuroleptics on phospholipase A2 (PLA2) activity in rat brain plasma membranes was studied. Chlorpromazine (10 mg/kg), fluphenazine (5 mg/kg), thioridazine (5 mg/kg), trifluoperazine (5 mg/kg), haloperidol (2 mg/kg), and sulpiride (100 mg/kg) were administered to rats intraperitoneally as a single dose or long-term treatment (4 weeks). The PLA2 activity was determined 24, 48, and 72 h after the last injection of a drug. The enzyme activity was decreased after a single or 4-week administration of chlorpromazine, trifluoperazine, haloperidol, and sulpiride. Fluphenazine and thioridazine caused an increase of PLA2 activity in rat brain both after a single dose and long-term administration. For the first time it was shown that neuroleptics cannot only inhibit but also increase, PLA2 activity. Elucidation of this fact requires further studies. PMID:7669826

  17. Loss of PLA2G6 leads to elevated mitochondrial lipid peroxidation and mitochondrial dysfunction

    PubMed Central

    Castillo-Quan, Jorge Iván; Bartolome, Fernando; Angelova, Plamena R.; Li, Li; Pope, Simon; Cochemé, Helena M.; Khan, Shabana; Asghari, Shabnam; Bhatia, Kailash P.; Hardy, John; Abramov, Andrey Y.; Partridge, Linda

    2015-01-01

    The PLA2G6 gene encodes a group VIA calcium-independent phospholipase A2 beta enzyme that selectively hydrolyses glycerophospholipids to release free fatty acids. Mutations in PLA2G6 have been associated with disorders such as infantile neuroaxonal dystrophy, neurodegeneration with brain iron accumulation type II and Karak syndrome. More recently, PLA2G6 was identified as the causative gene in a subgroup of patients with autosomal recessive early-onset dystonia-parkinsonism. Neuropathological examination revealed widespread Lewy body pathology and the accumulation of hyperphosphorylated tau, supporting a link between PLA2G6 mutations and parkinsonian disorders. Here we show that knockout of the Drosophila homologue of the PLA2G6 gene, iPLA2-VIA, results in reduced survival, locomotor deficits and organismal hypersensitivity to oxidative stress. Furthermore, we demonstrate that loss of iPLA2-VIA function leads to a number of mitochondrial abnormalities, including mitochondrial respiratory chain dysfunction, reduced ATP synthesis and abnormal mitochondrial morphology. Moreover, we show that loss of iPLA2-VIA is strongly associated with increased lipid peroxidation levels. We confirmed our findings using cultured fibroblasts taken from two patients with mutations in the PLA2G6 gene. Similar abnormalities were seen including elevated mitochondrial lipid peroxidation and mitochondrial membrane defects, as well as raised levels of cytoplasmic and mitochondrial reactive oxygen species. Finally, we demonstrated that deuterated polyunsaturated fatty acids, which inhibit lipid peroxidation, were able to partially rescue the locomotor abnormalities seen in aged flies lacking iPLA2-VIA gene function, and restore mitochondrial membrane potential in fibroblasts from patients with PLA2G6 mutations. Taken together, our findings demonstrate that loss of normal PLA2G6 gene activity leads to lipid peroxidation, mitochondrial dysfunction and subsequent mitochondrial membrane

  18. Active ratchets

    NASA Astrophysics Data System (ADS)

    Angelani, L.; Costanzo, A.; Di Leonardo, R.

    2011-12-01

    We analyze self-propelling organisms, or active particles, in a periodic asymmetric potential. Unlike standard ratchet effect for Brownian particles requiring external forcing, in the case of active particles asymmetric potential alone produces a net drift speed (active ratchet effect). By using theoretical models and numerical simulations we demonstrate the emergence of the rectification process in the presence of an asymmetric piecewise periodic potential. The broken spatial symmetry (external potential) and time symmetry (active particles) are sufficient ingredients to sustain unidirectional transport. Our findings open the way to new mechanisms to move in directional manner motile organisms by using external periodic static fields.

  19. Anti-PLA2R antibodies measured by ELISA predict long-term outcome in a prevalent population of patients with idiopathic membranous nephropathy.

    PubMed

    Kanigicherla, Durga; Gummadova, Jennet; McKenzie, Edward A; Roberts, Stephen A; Harris, Shelley; Nikam, Milind; Poulton, Kay; McWilliam, Lorna; Short, Colin D; Venning, Michael; Brenchley, Paul E

    2013-05-01

    Antibodies to the phospholipase A2 receptor 1 (PLA2R1) have been reported in 70% of cases of idiopathic membranous nephropathy (IMN). The genetic susceptibility of IMN has been accounted for by HLA DQA1 and PLA2R1 genes. Here we retrospectively quantified PLA2R antibodies by ELISA, and genotyped DQ alleles and PLA2R1 single-nucleotide polymorphisms for association with clinical criteria for disease activity at the time of first sample and with outcome over a median total follow-up of 90 months. In 90 prevalent patients with biopsy-proven IMN, anti-PLA2R antibodies were present in 75% of patients with IMN with active disease and were significantly higher than in patients in partial or complete remission at the time of antibody measurement. There was a differential IgG subclass response (4>2>3>1) at an early stage, i.e., within 6 months of biopsy. Levels of PLA2R antibodies were significantly linked to DQA1*05:01 and DQB1*02:01. Survival analysis of patients with IMN showed that PLA2R antibodies are significantly linked with outcome. Thus, high levels of PLA2R antibodies are linked with active disease and a higher risk of declining renal function during follow-up. Future therapeutic trials in IMN should monitor anti-PLA2R, as patients with a high antibody burden may benefit from earlier therapeutic intervention.

  20. Astronomy Activities.

    ERIC Educational Resources Information Center

    Greenstone, Sid

    This document consists of activities and references for teaching astronomy. The activities (which include objectives, list of materials needed, and procedures) focus on: observing the Big Dipper and locating the North Star; examining the Big Dipper's stars; making and using an astrolabe; examining retograde motion of Mars; measuring the Sun's…

  1. Faculty Activism

    ERIC Educational Resources Information Center

    Academe, 2005

    2005-01-01

    Blending scholarship and activism, whether domestic or international, takes some real work. Two scholar-activists reflect on why and how activism can be more than academic labor in this feature of the "Academe" journal. This feature includes the following brief reflections on political work, both local and global that demonstrates how on campus…

  2. Catalyst activator

    DOEpatents

    McAdon, Mark H.; Nickias, Peter N.; Marks, Tobin J.; Schwartz, David J.

    2001-01-01

    A catalyst activator particularly adapted for use in the activation of metal complexes of metals of Group 3-10 for polymerization of ethylenically unsaturated polymerizable monomers, especially olefins, comprising two Group 13 metal or metalloid atoms and a ligand structure including at least one bridging group connecting ligands on the two Group 13 metal or metalloid atoms.

  3. Outdoor Activities.

    ERIC Educational Resources Information Center

    Minneapolis Independent School District 275, Minn.

    Twenty-four activities suitable for outdoor use by elementary school children are outlined. Activities designed to make children aware of their environment include soil painting, burr collecting, insect and pond water collecting, studies of insect galls and field mice, succession studies, and a model of natural selection using dyed toothpicks. A…

  4. Rituximab-induced depletion of anti-PLA2R autoantibodies predicts response in membranous nephropathy.

    PubMed

    Beck, Laurence H; Fervenza, Fernando C; Beck, David M; Bonegio, Ramon G B; Malik, Fahim A; Erickson, Stephen B; Cosio, Fernando G; Cattran, Daniel C; Salant, David J

    2011-08-01

    Autoantibodies to the M-type phospholipase A(2) receptor (PLA(2)R) are sensitive and specific for idiopathic membranous nephropathy. The anti-B cell agent rituximab is a promising therapy for this disease, but biomarkers of early response to treatment currently do not exist. Here, we investigated whether levels of anti-PLA(2)R correlate with the immunological activity of membranous nephropathy, potentially exhibiting a more rapid response to treatment than clinical parameters such as proteinuria. We measured the amount of anti-PLA(2)R using Western blot immunoassay in serial serum samples from a total of 35 patients treated with rituximab for membranous nephropathy in two distinct cohorts. Pretreatment samples from 25 of 35 (71%) patients contained anti-PLA(2)R, and these autoantibodies declined or disappeared in 17 (68%) of these patients within 12 months after rituximab. Those who demonstrated this immunologic response fared better clinically: 59% and 88% attained complete or partial remission by 12 and 24 months, respectively, compared with 0% and 33% among those with persistent anti-PLA(2)R levels. Changes in antibody levels preceded changes in proteinuria. One subject who relapsed during follow-up had a concomitant return of anti-PLA(2)R. In summary, measuring anti-PLA(2)R levels by immunoassay may be a method to follow and predict response to treatment with rituximab in membranous nephropathy.

  5. Rituximab-Induced Depletion of Anti-PLA2R Autoantibodies Predicts Response in Membranous Nephropathy

    PubMed Central

    Fervenza, Fernando C.; Beck, David M.; Bonegio, Ramon G.B.; Malik, Fahim A.; Erickson, Stephen B.; Cosio, Fernando G.; Cattran, Daniel C.; Salant, David J.

    2011-01-01

    Autoantibodies to the M-type phospholipase A2 receptor (PLA2R) are sensitive and specific for idiopathic membranous nephropathy. The anti-B cell agent rituximab is a promising therapy for this disease, but biomarkers of early response to treatment currently do not exist. Here, we investigated whether levels of anti-PLA2R correlate with the immunological activity of membranous nephropathy, potentially exhibiting a more rapid response to treatment than clinical parameters such as proteinuria. We measured the amount of anti-PLA2R using Western blot immunoassay in serial serum samples from a total of 35 patients treated with rituximab for membranous nephropathy in two distinct cohorts. Pretreatment samples from 25 of 35 (71%) patients contained anti-PLA2R, and these autoantibodies declined or disappeared in 17 (68%) of these patients within 12 months after rituximab. Those who demonstrated this immunologic response fared better clinically: 59% and 88% attained complete or partial remission by 12 and 24 months, respectively, compared with 0% and 33% among those with persistent anti-PLA2R levels. Changes in antibody levels preceded changes in proteinuria. One subject who relapsed during follow-up had a concomitant return of anti-PLA2R. In summary, measuring anti-PLA2R levels by immunoassay may be a method to follow and predict response to treatment with rituximab in membranous nephropathy. PMID:21784898

  6. Expression of Phospholipases A2 in Primary Human Lung Macrophages. Role of Cytosolic Phospholipase A2–α in Arachidonic Acid Release and Platelet Activating Factor Synthesis

    PubMed Central

    Giannattasio, Giorgio; Lai, Ying; Granata, Francescopaolo; Mounier, Carine M.; Nallan, Laxman; Oslund, Rob; Leslie, Christina C.; Marone, Gianni; Lambeau, Gérard; Gelb, Michael H.; Triggiani, Massimo

    2009-01-01

    Summary Macrophages are a major source of lipid mediators in the human lung. Expression and contribution of cytosolic (cPLA2) and secreted phospholipases A2 (sPLA2) to the generation of lipid mediators in human macrophages is unclear. We investigated the expression and role of different PLA2s in the production of lipid mediators in primary human lung macrophages. Macrophages express the alpha, but not the zeta isoform of group IV and group VIA cPLA2 (iPLA2). Two structurally-divergent inhibitors of group IV cPLA2 completely block arachidonic acid release by macrophages in response to non-physiological (Ca2+ ionophores and phorbol esters) and physiological agonists (lipopolysaccharide and Mycobacterium protein derivative). These inhibitors also reduce by 70% the synthesis of platelet-activating factor by activated macrophages. Among the full set of human sPLA2s, macrophages express group IIA, IID, IIE, IIF, V, X and XIIA, but not group IB and III enzymes. Me-Indoxam, a potent and cell impermeable inhibitor of several sPLA2s, has no effect on arachidonate release or platelet-activating factor production. Agonist-induced exocytosis is not influenced by cPLA2 inhibitors at concentrations that block arachidonic acid release. Our results indicate that human macrophages express cPLA2-alpha, iPLA2 and several sPLA2s. Cytosolic PLA2-alpha is the major enzyme responsible for lipid mediator production in human macrophages. PMID:19130898

  7. Activation of lactoperoxidase system in milk by glucose oxidase immobilized in electrospun polylactide microfibers.

    PubMed

    Zhou, Y; Lim, L-T

    2009-03-01

    In this study, glucose oxidase (GOX) was immobilized in polylactide (PLA) fibers that were used to activate the lactoperoxidase (LP) system in milk. The GOX-containing microfibers were electrospun from emulsions prepared by dispersing aqueous GOX in PLA dissolved in a chloroform and N,N-dimethylformamide blend, using sorbitan monopalmitate as an emulsifier. The enzymatic activity of GOX-in-PLA fibers (1100 +/- 400 nm diameter) was more than 19 times higher than that of the GOX-in-PLA membrane formed by direct casting, due to the larger surface area of the electrospun fibers. The activation of LP in model solutions using GOX-in-PLA fibers provided a more sustained generation of antimicrobial OSCN(-) than direct activation using H(2)O(2). Preliminary evaluation on milk samples showed that the electrospun GOX-in-PLA microfibers are capable of activating the naturally present LP system, indicating that they may be promising for active food packaging applications to extend the shelf life of milk.

  8. Activation of lactoperoxidase system in milk by glucose oxidase immobilized in electrospun polylactide microfibers.

    PubMed

    Zhou, Y; Lim, L-T

    2009-03-01

    In this study, glucose oxidase (GOX) was immobilized in polylactide (PLA) fibers that were used to activate the lactoperoxidase (LP) system in milk. The GOX-containing microfibers were electrospun from emulsions prepared by dispersing aqueous GOX in PLA dissolved in a chloroform and N,N-dimethylformamide blend, using sorbitan monopalmitate as an emulsifier. The enzymatic activity of GOX-in-PLA fibers (1100 +/- 400 nm diameter) was more than 19 times higher than that of the GOX-in-PLA membrane formed by direct casting, due to the larger surface area of the electrospun fibers. The activation of LP in model solutions using GOX-in-PLA fibers provided a more sustained generation of antimicrobial OSCN(-) than direct activation using H(2)O(2). Preliminary evaluation on milk samples showed that the electrospun GOX-in-PLA microfibers are capable of activating the naturally present LP system, indicating that they may be promising for active food packaging applications to extend the shelf life of milk. PMID:19323732

  9. Activation analysis

    SciTech Connect

    Alfassi, Z.B. . Dept. of Nuclear Engineering)

    1990-01-01

    This volume contains 16 chapters on the application of activation analysis in the fields of life sciences, biological materials, coal and its effluents, environmental samples, archaeology, material science, and forensics. Each chapter is processed separately for the data base.

  10. Biodegradable micelles enhance the antiglioma activity of curcumin in vitro and in vivo.

    PubMed

    Zheng, Songping; Gao, Xiang; Liu, Xiaoxiao; Yu, Ting; Zheng, Tianying; Wang, Yi; You, Chao

    2016-01-01

    Curcumin (Cur), a natural polyphenol of Curcuma longa, has been recently reported to possess antitumor activities. However, due to its poor aqueous solubility and low biological availability, the clinical application of Cur is quite limited. The encapsulation of hydrophobic drugs into nanoparticles is an effective way to improve their pharmaceutical activities. In this research, nanomicelles loaded with Cur were formulated by a self-assembly method with biodegradable monomethoxy poly(ethylene glycol)-poly(lactide) copolymers (MPEG-PLAs). After encapsulation, the cellular uptake was increased and Cur could be released from MPEG-PLA micelles in a sustained manner. The Cur-loaded MPEG-PLA micelles (Cur/MPEG-PLA micelles) exhibited an enhanced toxicity on C6 and U251 glioma cells and induced more apoptosis on C6 glioma cells compared with free Cur. Moreover, the therapy efficiency of Cur/MPEG-PLA micelles was evaluated at length on a nude mouse model bearing glioma. The Cur/MPEG-PLA micelles were more effective on suppressing tumor growth compared with free Cur, which indicated that Cur/MPEG-PLA micelles improved the antiglioma activity of Cur in vivo. The results of immunohistochemical and immunofluorescent analysis indicated that the induction of apoptosis, antiangiogenesis, and inhibition of cell proliferation may contribute to the improvement in antiglioma effects. Our data suggested that Cur/MPEG-PLA may have potential clinic applications in glioma therapy. PMID:27354801

  11. Biodegradable micelles enhance the antiglioma activity of curcumin in vitro and in vivo

    PubMed Central

    Zheng, Songping; Gao, Xiang; Liu, Xiaoxiao; Yu, Ting; Zheng, Tianying; Wang, Yi; You, Chao

    2016-01-01

    Curcumin (Cur), a natural polyphenol of Curcuma longa, has been recently reported to possess antitumor activities. However, due to its poor aqueous solubility and low biological availability, the clinical application of Cur is quite limited. The encapsulation of hydrophobic drugs into nanoparticles is an effective way to improve their pharmaceutical activities. In this research, nanomicelles loaded with Cur were formulated by a self-assembly method with biodegradable monomethoxy poly(ethylene glycol)-poly(lactide) copolymers (MPEG-PLAs). After encapsulation, the cellular uptake was increased and Cur could be released from MPEG-PLA micelles in a sustained manner. The Cur-loaded MPEG-PLA micelles (Cur/MPEG-PLA micelles) exhibited an enhanced toxicity on C6 and U251 glioma cells and induced more apoptosis on C6 glioma cells compared with free Cur. Moreover, the therapy efficiency of Cur/MPEG-PLA micelles was evaluated at length on a nude mouse model bearing glioma. The Cur/MPEG-PLA micelles were more effective on suppressing tumor growth compared with free Cur, which indicated that Cur/MPEG-PLA micelles improved the antiglioma activity of Cur in vivo. The results of immunohistochemical and immunofluorescent analysis indicated that the induction of apoptosis, antiangiogenesis, and inhibition of cell proliferation may contribute to the improvement in antiglioma effects. Our data suggested that Cur/MPEG-PLA may have potential clinic applications in glioma therapy. PMID:27354801

  12. Short-term fenofibrate treatment reduces elevated plasma Lp-PLA2 mass and sVCAM-1 levels in a subcohort of hypertriglyceridemic GOLDN participants

    Technology Transfer Automated Retrieval System (TEKTRAN)

    High levels of lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) are associated with inflammation, atherosclerosis, and coronary heart disease events. In addition, Lp-PLA(2) has been linked to classical markers of endothelial activation, including soluble vascular cell adhesion molecule-1 (sVCAM...

  13. Phospholipase A2 activity is associated with structural brain changes in schizophrenia.

    PubMed

    Smesny, Stefan; Milleit, Berko; Nenadic, Igor; Preul, Christoph; Kinder, Daniel; Lasch, Jürgen; Willhardt, Ingo; Sauer, Heinrich; Gaser, Christian

    2010-10-01

    Regional structural brain changes are among the most robust biological findings in schizophrenia, yet the underlying pathophysiological changes remain poorly understood. Recent evidence suggests that abnormal neuronal/dendritic plasticity is related to alterations in membrane lipids. We examined whether serum activity of membrane lipid remodelling/repairing cytosolic phospholipase A(2) (PLA(2)) were related to regional brain structure in magnetic resonance images (MRI). The study involved 24 schizophrenia patients, who were either drug-naïve or off antipsychotic medication, and 25 healthy controls. Using voxel-based morphometry (VBM) analysis of T1-high-resolution MRI-images, we correlated both gray matter and white matter changes with serum PLA(2)-activity. PLA(2) activity was increased in patients, consistent with previous findings. VBM group comparison of patients vs. controls showed abnormalities of frontal and medial temporal cortices/hippocampus, and left middle/superior temporal gyrus in first-episode patients. Group comparison of VBM/PLA(2)-correlations revealed a distinct pattern of disease-related interactions between gray/white matter changes in patients and PLA(2)-activity: in first-episode patients (n=13), PLA(2)-activity was associated with structural alterations in the left prefrontal cortex and the bilateral thalamus. Recurrent-episode patients (n=11) showed a wide-spread pattern of associations between PLA(2)-activity and structural changes in the left (less right) prefrontal and inferior parietal cortex, the left (less right) thalamus and caudate nucleus, the left medial temporal and orbitofrontal cortex and anterior cingulum, and the cerebellum. Our findings demonstrate a potential association between membrane lipid biochemistry and focal brain structural abnormalities in schizophrenia. Differential patterns in first-episode vs. chronic patients might be related to PLA(2)-increase at disease-onset reflecting localized regenerative activity

  14. Inactivation of Peroxiredoxin 6 by the Pla Protease of Yersinia pestis

    PubMed Central

    Zimbler, Daniel L.; Eddy, Justin L.; Schroeder, Jay A.

    2015-01-01

    Pneumonic plague represents the most severe form of disease caused by Yersinia pestis due to its ease of transmission, rapid progression, and high mortality rate. The Y. pestis outer membrane Pla protease is essential for the development of pneumonic plague; however, the complete repertoire of substrates cleaved by Pla in the lungs is not known. In this study, we describe a proteomic screen to identify host proteins contained within the bronchoalveolar lavage fluid of mice that are cleaved and/or processed by Y. pestis in a Pla-dependent manner. We identified peroxiredoxin 6 (Prdx6), a host factor that contributes to pulmonary surfactant metabolism and lung defense against oxidative stress, as a previously unknown substrate of Pla. Pla cleaves Prdx6 at three distinct sites, and these cleavages disrupt both the peroxidase and phospholipase A2 activities of Prdx6. In addition, we found that infection with wild-type Y. pestis reduces the abundance of extracellular Prdx6 in the lungs compared to that after infection with Δpla Y. pestis, suggesting that Pla cleaves Prdx6 in the pulmonary compartment. However, following infection with either wild-type or Δpla Y. pestis, Prdx6-deficient mice exhibit no differences in bacterial burden, host immune response, or lung damage from wild-type mice. Thus, while Pla is able to disrupt Prdx6 function in vitro and reduce Prdx6 levels in vivo, the cleavage of Prdx6 has little detectable impact on the progression or outcome of pneumonic plague. PMID:26553463

  15. Recurrent membranous nephropathy in an allograft caused by IgG3κ targeting the PLA2 receptor.

    PubMed

    Debiec, Hanna; Hanoy, Melanie; Francois, Arnaud; Guerrot, Dominique; Ferlicot, Sophie; Johanet, Catherine; Aucouturier, Pierre; Godin, Michel; Ronco, Pierre

    2012-12-01

    Up to 80% of patients with idiopathic membranous nephropathy have non-complement-fixing IgG4 autoantibodies to the phospholipase A2 receptor (PLA2R). Membranous nephropathy recurs in approximately 40% of patients after kidney transplantation, but the mechanism is unknown. Here, we describe a patient with recurrent membranous nephropathy 13 days after kidney transplantation whose graft biopsy specimen showed granular staining for C3, C5b-9, C1q, and IgG3κ; electron microscopy revealed subepithelial nonorganized deposits. A search for hematologic disorders was negative. Retrospective evaluation of a biopsy sample from the native kidney revealed a similar pattern: monotypic IgG3κ deposits together with C3, C1q, and C5b-9. Glomerular deposits contained PLA2R in both the graft and the native kidney, suggesting that the recurrence was the result of circulating anti-PLA2R antibodies binding to PLA2R antigen expressed on donor podocytes. Confocal analysis of anti-PLA2R and antihuman IgG3 showed co-localization, and the patient had IgG3κ-restricted circulating anti-PLA2R antibodies. Treatment with rituximab stabilized both proteinuria and serum creatinine, and circulating anti-PLA2R became undetectable. In summary, this case of recurrent membranous nephropathy in a graft suggests that circulating monoclonal anti-PLA2R IgG3κ caused the disease and activated complement by the classic pathway.

  16. Integrin activation

    PubMed Central

    Ginsberg, Mark H.

    2014-01-01

    Integrin-mediated cell adhesion is important for development, immune responses, hemostasis and wound healing. Integrins also function as signal transducing receptors that can control intracellular pathways that regulate cell survival, proliferation, and cell fate. Conversely, cells can modulate the affinity of integrins for their ligands a process operationally defined as integrin activation. Analysis of activation of integrins has now provided a detailed molecular understanding of this unique form of “inside-out” signal transduction and revealed new paradigms of how transmembrane domains (TMD) can transmit long range allosteric changes in transmembrane proteins. Here, we will review how talin and mediates integrin activation and how the integrin TMD can transmit these inside out signals. [BMB Reports 2014; 47(12): 655-659] PMID:25388208

  17. Active Cytokinins

    PubMed Central

    Mornet, René; Theiler, Jane B.; Leonard, Nelson J.; Schmitz, Ruth Y.; Moore, F. Hardy; Skoog, Folke

    1979-01-01

    Four series of azidopurines have been synthesized and tested for cytokinin activity in the tobacco callus bioassay: 2- and 8-azido-N6-benzyladenines, -N6-(Δ2-isopentenyl)adenines, and -zeatins, and N6-(2- and 4-azidobenzyl)adenines. The compounds having 2-azido substitution on the adenine ring are as active as the corresponding parent compounds, while those with 8-azido substitution are about 10 or more times as active. The 8-azidozeatin, which is the most active cytokinin observed, exhibited higher than minimal detectable activity at 1.2 × 10−5 micromolar, the lowest concentration tested. The shape of the growth curve indicates that even a concentration as low as 5 × 10−6 micromolar would probably be effective. By comparison, the lowest active concentration ever reported for zeatin has been 5 × 10−5 micromolar, representing a sensitivity rarely attained. All of the azido compounds have been submitted to photolysis in aqueous ethanol, and the photoproducts have been detected and identified by low and high resolution mass spectrometry. They are rationalized as products of abstraction and insertion reactions of the intermediate nitrenes. The potential of the major released products as cytokinins was also assessed by bioassay. 2-Azido-N6-(Δ2-isopentenyl)adenine competed with [14C]kinetin for the cytokinin-binding protein isolated from wheat germ. When the azido compound was photolysed in the presence of this protein, its attachment effectively blocked the binding of [14C]kinetin. PMID:16661017

  18. Structural analysis of Pla protein from the biological warfare agent Yersinia pestis: docking and molecular dynamics of interactions with the mammalian plasminogen system.

    PubMed

    Ruback, Eduardo; Lobo, Leandro Araujo; França, Tanos Celmar Costa; Pascutti, Pedro Geraldo

    2013-01-01

    Yersinia pestis protein Pla is a plasmid-coded outer membrane protein with aspartic-protease activity. Pla exhibits a plasminogen (Plg) activator activity (PAA) that promotes the cleavage of Plg to the active serine-protease form called plasmin. Exactly how Pla activates Plg into plasmin remains unclear. To investigate this event, we performed the interactions between the predicted Plg and Pla protein structures by rigid-body docking with the HEX program and evaluated the complex stability by molecular dynamics (MD) using the GROMACS package programs. The predicted docked complex of Plg-Pla shows the same interaction site predicted by experimental site-direct mutagenesis in other studies. After a total of 8 ns of MD simulation, we observed the relaxation of the beta-barrel structure of Pla and the progressive approximation and stabilization between the cleavage site of Plg into the extracellular loops of Pla, followed by the increase in the number of H bonds. We also report here the aminoacids that participate in the active site and the sub sites of interaction. The total understanding of these interactions can be an important tool for drug design against bacterial proteases.

  19. Active microwaves

    NASA Technical Reports Server (NTRS)

    Evans, D.; Vidal-Madjar, D.

    1994-01-01

    Research on the use of active microwaves in remote sensing, presented during plenary and poster sessions, is summarized. The main highlights are: calibration techniques are well understood; innovative modeling approaches have been developed which increase active microwave applications (segmentation prior to model inversion, use of ERS-1 scatterometer, simulations); polarization angle and frequency diversity improves characterization of ice sheets, vegetation, and determination of soil moisture (X band sensor study); SAR (Synthetic Aperture Radar) interferometry potential is emerging; use of multiple sensors/extended spectral signatures is important (increase emphasis).

  20. [Lp-PLA2, a biomarker of vascular inflammation and vulnerability of atherosclerosis plaques].

    PubMed

    Bonnefont-Rousselot, D

    2016-05-01

    A chronic inflammation is involved in various stages of development of the atherosclerotic plaques. Among the emerging biomarkers of atherogenesis, the lipoprotein-associated phospholipase A2 (Lp-PLA2), formerly known as PAF-acetylhydrolase (McIntyre et al., 2009), hydrolyses the oxidized short chain phospholipids of low-density lipoproteins (LDL), thereby releasing pro-inflammatory mediators (lysophospholipids and oxidized fatty acids). Lp-PLA2, produced by monocytes/macrophages and T-lymphocytes, and mainly associated with LDL (Gazi et al., 2005), is predominantly expressed in the necrotic center of the atherosclerotic plaques and in the macrophage-rich areas (Kolodgie et al., 2006). It would have a predictive role of cardiovascular (CV) events in relation to the vulnerability of atherosclerotic plaques. Determination of Lp-PLA2 has been proposed in the assessment of the CV risk, to ensure a better stratification of populations at intermediate risk for targeted therapy (Davidson et al., 2008). Its proatherogenic role suggested that inhibition of its activity could ensure a better vascular protection in combination with cholesterol-lowering agents. Nevertheless, Lp-PLA2 is not yet a fully validated marker for use in daily clinical practice, especially since the studies using an inhibitor of Lp-PLA2 (darapladib) (STABILITY Investigators et al., 2014; O'Donoghue et al., 2014) did not show any reduction in coronary events. Lp-PLA2 could have a site-specific role in plaque inflammation and development (Fenning et al., 2015). High Lp-PLA2 activity could reflect a response to pro-inflammatory stress characteristic of atherosclerosis (Marathe et al., 2014). This presentation aims at clarifying the involvement of Lp-PLA2 in the pathophysiology of atherosclerosis, and at assessing its interest both as a biomarker for the onset of CV events and as a therapeutic target. PMID:26499399

  1. Porous poly(DL-lactic acid) matrix film with antimicrobial activities for wound dressing application.

    PubMed

    Chitrattha, Sasiprapa; Phaechamud, Thawatchai

    2016-01-01

    Poly(lactic acid) (PLA) is polymeric biomaterial that has been used for wound dressing due to its biodegradability and biocompatibility. However, PLA has some limitations including poor toughness, low degradation rate and high hydrophobicity. The aim of this study is to develop an antibiotic drug-loaded PLA porous film as wound dressing with antibacterial activity. PLA porous film was fabricated by temperature change technique using solvent casting method. Polyethylene glycol (PEG) 400 was added for improving the pore interconnectivity of film. Gentamicin sulfate (GS) or metronidazole (MZ) was incorporated into PLA porous films. PLA containing PEG 400 exhibited the more amorphous form than plain PLA film and contained 55.31 ± 2.85% porosity and 20 μm of the pore size which significantly improved the water vapor transmission rate, oxygen transmission rate, degradation rate and percentage of drug release, respectively. Drug-loaded porous films efficiently inhibited the bacteria growth. GS-loaded film inhibited Staphylococcus aureus, Proteus mirabilis, Pseudomonas aeruginosa, whereas MZ-loaded film inhibited Bacteroides fragilis and the sustainable antibacterial activity was attained for 7 days.

  2. Porous poly(DL-lactic acid) matrix film with antimicrobial activities for wound dressing application.

    PubMed

    Chitrattha, Sasiprapa; Phaechamud, Thawatchai

    2016-01-01

    Poly(lactic acid) (PLA) is polymeric biomaterial that has been used for wound dressing due to its biodegradability and biocompatibility. However, PLA has some limitations including poor toughness, low degradation rate and high hydrophobicity. The aim of this study is to develop an antibiotic drug-loaded PLA porous film as wound dressing with antibacterial activity. PLA porous film was fabricated by temperature change technique using solvent casting method. Polyethylene glycol (PEG) 400 was added for improving the pore interconnectivity of film. Gentamicin sulfate (GS) or metronidazole (MZ) was incorporated into PLA porous films. PLA containing PEG 400 exhibited the more amorphous form than plain PLA film and contained 55.31 ± 2.85% porosity and 20 μm of the pore size which significantly improved the water vapor transmission rate, oxygen transmission rate, degradation rate and percentage of drug release, respectively. Drug-loaded porous films efficiently inhibited the bacteria growth. GS-loaded film inhibited Staphylococcus aureus, Proteus mirabilis, Pseudomonas aeruginosa, whereas MZ-loaded film inhibited Bacteroides fragilis and the sustainable antibacterial activity was attained for 7 days. PMID:26478412

  3. Activity report

    SciTech Connect

    Yu, S W

    2008-08-11

    This report is aimed to show the author's activities to support the LDRD. The title is 'Investigation of the Double-C Behavior in the Pu-Ga Time-Temperature-Transformation Diagram' The sections are: (1) Sample Holder Test; (2) Calculation of x-ray diffraction patterns; (3) Literature search and preparing publications; (4) Tasks Required for APS Experiments; and (5) Communications.

  4. Classroom Activities.

    ERIC Educational Resources Information Center

    Stuart, Frances R.

    This pamphlet suggests activities that may be used in the elementary school classroom. Chapter I lists various short plays that children can easily perform which encourage their imagination. Chapter II details a few quiet classroom games such as "I Saw,""Corral the Wild Horse,""Who Has Gone from the Room," and "Six-Man-Football Checkers." A number…

  5. Learning Activities.

    ERIC Educational Resources Information Center

    Tipton, Tom, Ed.

    1983-01-01

    Presents a flow chart for naming inorganic compounds. Although it is not necessary for students to memorize rules, preliminary skills needed before using the chart are outlined. Also presents an activity in which the mass of an imaginary atom is determined using lead shot, Petri dishes, and a platform balance. (JN)

  6. Leaf Activities.

    ERIC Educational Resources Information Center

    Mingie, Walter

    Leaf activities can provide a means of using basic concepts of outdoor education to learn in elementary level subject areas. Equipment needed includes leaves, a clipboard with paper, and a pencil. A bag of leaves may be brought into the classroom if weather conditions or time do not permit going outdoors. Each student should pick a leaf, examine…

  7. Get Active

    MedlinePlus

    ... Lifting small weights – you can even use bottled water or cans of food as weights Watch these videos for muscle strengthening exercises to do at home or at the gym. If you do muscle-strengthening activities with weights, check out the do’s and don’ ...

  8. Activated Sludge.

    ERIC Educational Resources Information Center

    Saunders, F. Michael

    1978-01-01

    Presents the 1978 literature review of wastewater treatment. This review covers: (1) activated sludge process; (2) process control; (3) oxygen uptake and transfer; (4) phosphorus removal; (5) nitrification; (6) industrial wastewater; and (7) aerobic digestion. A list of 136 references is also presented. (HM)

  9. Orthopaedic applications for PLA-PGA biodegradable polymers.

    PubMed

    Athanasiou, K A; Agrawal, C M; Barber, F A; Burkhart, S S

    1998-10-01

    Biodegradable polymers, especially those belonging to the family of polylactic acid (PLA) and polyglycolic acid (PGA), play an increasingly important role in orthopaedics. These polymers degrade by hydrolysis and enzymatic activity and have a range of mechanical and physical properties that can be engineered appropriately to suit a particular application. Their degradation characteristics depend on several parameters including their molecular structure, crystallinity, and copolymer ratio. These biomaterials are also rapidly gaining recognition in the fledging field of tissue engineering because they can be fashioned into porous scaffolds or carriers of cells, extracellular matrix components, and bioactive agents. Although their future appears to be bright, several questions regarding the biocompatibility of these materials linger and should be addressed before their wide-scale use. In the context of musculoskeletal tissue, this report provides a comprehensive review of properties and applications of biodegradable PLA/PGA polymers and their copolymers. Of special interest are orthopaedic applications, biocompatibility studies, and issues of sterilization and storage of these versatile biomaterials. Also discussed is the fact that terms such as PLA, PGA, or PLA-PGA do not denote one material, but rather a large family of materials that have a wide range of differing bioengineering properties and concomitant biological responses. An analysis of some misconceptions, problems, and potential solutions is also provided. PMID:9788368

  10. A model to study physiological activation of phospholipase A sub 2 and vasorelaxation by lysophosphatidylcholine

    SciTech Connect

    Menon, N.K.; Pataricza, J.; Zehetgruber, M.; Bing, R.J. )

    1990-01-01

    Earlier we demonstrated that micellar solutions of LPC caused endothelium-dependent relaxation of rabbit thoracic aorta and bovine intrapulmonary artery and vein through a cyclic GMP-dependent mechanism. The availability of LPC for vasorelaxation depends on its production by deacylation of PC by PLA{sub 2}. We assessed the possible activation of PLA{sub 2} by commonly used vasorelaxants such as acetylcholine, bradykinin, calcium ionophore A23187 and thrombin and vasoconstrictors like histamine and phenylephrine in the presence of indomethacin in a model system where {sup 14}C PC was incorporated into bovine intrapulmonary arterial segments. Taking the ratio of {sup 14}C PC:LPC formed by exogenous PLA{sub 2} as an index of deacylation, we found that while all the agents relaxed the strips in an endothelium-dependent manner, only thrombin caused relaxation followed by an increase in {sup 14}C LPC and a concomittant decrease in {sup 14}C PC indicating activation of PLA{sub 2}. Our data show that PC/PLA{sub 2} system can be activated to generate LPC for vascular relaxation under specific physiological conditions. This model system can be used to monitor PLA{sub 2} activity and LPC production to compensate flow and pressure induced changes in arteries.

  11. The standard aqueous stem bark extract of Mangifera indica L. inhibits toxic PLA2 - NN-XIb-PLA2 of Indian cobra venom.

    PubMed

    Dhananjaya, Bhadrapura Lakkappa; Sudarshan, Shivalingaiah; Dongol, Yashad; More, Sunil S

    2016-05-01

    The aqueous extract of Mangifera indica is known to possess diverse medicinal properties, which also includes anti-snake venom activities. However, its inhibitory potency and mechanism of action on multi-toxic snake venom phospholipases A2s are still unknown. Therefore, the objective of this study was to evaluate the modulatory effect of standard aqueous bark extract of M. indica on NN-XIb-PLA2 of Indian cobra venom. The in vitro sPLA2, in situ hemolytic and in vivo edema inhibition effect were carried out as described. Also the effect of substrate and calcium concentration was carried out. M. indica extract dose dependently inhibited the GIA sPLA2 (NN-XIb-PLA2) activity with an IC50 value of 7.6 μg/ml. M. indica extract effectively inhibited the indirect hemolytic activity up to 98% at ∼40 μg/ml concentration. Further, M. indica extract (0-50 μg/ml) inhibited the edema formed in a dose dependent manner. When examined as a function of increased substrate and calcium concentration, there was no relieve of inhibitory effect of M. indica extract on the NN-XIb-PLA2. Further, the inhibition was irreversible as evident from binding studies. The in vitro inhibition is well correlated with in situ and in vivo edema inhibiting activities of M. indica. As the inhibition is independent of substrate and calcium and was irreversible, it can be concluded that M. indica extract mode of inhibition could be due to direct interaction of components present in the extract with the PLA2 enzyme. The aqueous extract of M. indica effectively inhibits svPLA2 enzymatic and its associated toxic activities, which substantiate their anti-snake venom properties. Further in-depth studies on the role and mechanism of the principal constituents present in the extract, responsible for the anti-PLA2 activity will be interesting to develop them into potent antisnake component and also as an anti-inflammatory agent.

  12. The standard aqueous stem bark extract of Mangifera indica L. inhibits toxic PLA2 - NN-XIb-PLA2 of Indian cobra venom.

    PubMed

    Dhananjaya, Bhadrapura Lakkappa; Sudarshan, Shivalingaiah; Dongol, Yashad; More, Sunil S

    2016-05-01

    The aqueous extract of Mangifera indica is known to possess diverse medicinal properties, which also includes anti-snake venom activities. However, its inhibitory potency and mechanism of action on multi-toxic snake venom phospholipases A2s are still unknown. Therefore, the objective of this study was to evaluate the modulatory effect of standard aqueous bark extract of M. indica on NN-XIb-PLA2 of Indian cobra venom. The in vitro sPLA2, in situ hemolytic and in vivo edema inhibition effect were carried out as described. Also the effect of substrate and calcium concentration was carried out. M. indica extract dose dependently inhibited the GIA sPLA2 (NN-XIb-PLA2) activity with an IC50 value of 7.6 μg/ml. M. indica extract effectively inhibited the indirect hemolytic activity up to 98% at ∼40 μg/ml concentration. Further, M. indica extract (0-50 μg/ml) inhibited the edema formed in a dose dependent manner. When examined as a function of increased substrate and calcium concentration, there was no relieve of inhibitory effect of M. indica extract on the NN-XIb-PLA2. Further, the inhibition was irreversible as evident from binding studies. The in vitro inhibition is well correlated with in situ and in vivo edema inhibiting activities of M. indica. As the inhibition is independent of substrate and calcium and was irreversible, it can be concluded that M. indica extract mode of inhibition could be due to direct interaction of components present in the extract with the PLA2 enzyme. The aqueous extract of M. indica effectively inhibits svPLA2 enzymatic and its associated toxic activities, which substantiate their anti-snake venom properties. Further in-depth studies on the role and mechanism of the principal constituents present in the extract, responsible for the anti-PLA2 activity will be interesting to develop them into potent antisnake component and also as an anti-inflammatory agent. PMID:27275129

  13. Glucokinase activators.

    PubMed

    Filipski, Kevin J; Futatsugi, Kentaro; Pfefferkorn, Jeffrey A; Stevens, Benjamin D

    2012-07-01

    In this review we highlight recently disclosed progress in the field of small-molecule activators of the human glucokinase enzyme. Several of the reported chemotypes possess structural features that diverge from known leads; some of these modifications appear to be specifically designed to modulate tissue selectivity or discrete parameters of enzyme function (e.g., S0.5 v Vmax). This review will inform the reader of the extent of continued effort being directed toward discovery of a first-in-class drug for Type II diabetes mellitus that functions through this target. Patents were selected from those published in December 2009 up to November 2011; foreign filings were translated where possible to understand the claims and biological techniques utilized to characterize the reported glucokinase activators. Overall, there appears to be a recent trend leading to reduced patent filings for small-molecule glucokinase activators. There are many possible explanations for this trend; however, it is likely that the field has reached maturity and that the downturn of new disclosures represents the transition of many of these programs to the clinic.

  14. Survival of Haplorchis taichui metacercariae in Lab-Pla, Thai traditional food preparation.

    PubMed

    Chuboon, Suksan; Wongsawad, Chalobol; Ruamsuk, Archaree; Nithikathkul, Chusak

    2005-01-01

    Lab-Pla is a famous kind of Thai traditional food in northern and northeasthern Thailand. Consumption of uncooked Lab-Pla can lead to trematode infection because cyprinoid fish serve as the 2nd intermediate hosts of trematodes. The preparation of Lab-Pla can be made in different ways, depending on seasonings used in different places. The effect of the seasonings used in Lab-Pla on the survival of Haplorchis taichui metacercariae were, therefore, determined. The methodology was done by the following: 100 g of chopped Siamese mud carp fish (Henicorhynchus siamensis) were used for each experiment of seasonings used for completely mixed Lab-Pla. Mixed materials were blended and digested by 1% pepsin solution to obtain metacercariae and then checked for the movement under a stereomicroscope. The results showed that metacercariae remained active in 5 experimental groups: fermented fish treated, fish sauce treated, chili powder treated, ground roasted rice treated, and complete mixed treated indicated by average as follows: 27, 38.7, 33.3, 42.7 and 21%, respectively. In conclusion, fermented fish and completely mixed methods have more effectiveness in killing metacercariae in Lab-Pla preparation than other seasonings (p < 0.05).

  15. Mechanical properties and shape memory effect of 3D-printed PLA-based porous scaffolds.

    PubMed

    Senatov, F S; Niaza, K V; Zadorozhnyy, M Yu; Maksimkin, A V; Kaloshkin, S D; Estrin, Y Z

    2016-04-01

    In the present work polylactide (PLA)/15wt% hydroxyapatite (HA) porous scaffolds with pre-modeled structure were obtained by 3D-printing by fused filament fabrication. Composite filament was obtained by extrusion. Mechanical properties, structural characteristics and shape memory effect (SME) were studied. Direct heating was used for activation of SME. The average pore size and porosity of the scaffolds were 700μm and 30vol%, respectively. Dispersed particles of HA acted as nucleation centers during the ordering of PLA molecular chains and formed an additional rigid fixed phase that reduced molecular mobility, which led to a shift of the onset of recovery stress growth from 53 to 57°C. A more rapid development of stresses was observed for PLA/HA composites with the maximum recovery stress of 3.0MPa at 70°C. Ceramic particles inhibited the growth of cracks during compression-heating-compression cycles when porous PLA/HA 3D-scaffolds recovered their initial shape. Shape recovery at the last cycle was about 96%. SME during heating may have resulted in "self-healing" of scaffold by narrowing the cracks. PLA/HA 3D-scaffolds were found to withstand up to three compression-heating-compression cycles without delamination. It was shown that PLA/15%HA porous scaffolds obtained by 3D-printing with shape recovery of 98% may be used as self-fitting implant for small bone defect replacement owing to SME.

  16. Biodegradable PLA (polylactic acid) hinged trays keep quality of fresh-cut and cooked spinach.

    PubMed

    Botondi, Rinaldo; Bartoloni, Serena; Baccelloni, Simone; Mencarelli, Fabio

    2015-09-01

    This work examines the effects of packaging using two different polymeric trays with hinged lids, polyethylene terephthalate (PET) and polylactic acid (PLA), on fresh-cut and cooked spinach (Spinacia oleracea). Samples were stored in a cold room for 16 days at 4 °C. Chemical (total pigments, total polyphenols, ascorbic acid, antioxidant activity), physical (water activity), technological (colour evaluation), sensorial (aroma, visual appearance and water accumulation) and microbial (total aerobic mesophilic and psychrotrophic counts) parameters were tested. Both polymeric trays maintained the overall quality of fresh spinach for 6 days but spinach stored in PLA trays maintained its flavour longer. A significant increase in total polyphenols, antiradical activity, total carotenoids as well as a decrease in ascorbic acid in fresh spinach was observed in the first 3 days of storage in both samples. Unfortunately, the PLA package accumulated condensed water. The total microbial load of fresh-cut spinach reached about 6.3-7.3 log CFU g(-1) within 8 days. Cooked spinach packed in PLA and PET polymeric hinged trays showed the same behaviour as fresh spinach in terms of quality and shelf life. In conclusion, PLA plastic hinged trays can be used for packaging fresh-cut and cooked cut spinach, but the problem of condensed water must be solved. PMID:26345011

  17. Enhanced efficacy of clindamycin hydrochloride encapsulated in PLA/PLGA based nanoparticle system for oral delivery.

    PubMed

    Rauta, Pradipta Ranjan; Das, Niladri Mohan; Nayak, Debasis; Ashe, Sarbani; Nayak, Bismita

    2016-08-01

    Clindamycin hydrochloride (CLH) is a clinically important oral antibiotic with wide spectrum of antimicrobial activity that includes gram-positive aerobes (staphylococci, streptococci etc.), most anaerobic bacteria, Chlamydia and certain protozoa. The current study was focused to develop a stabilised clindamycin encapsulated poly lactic acid (PLA)/poly (D,L-lactide-co-glycolide) (PLGA) nano-formulation with better drug bioavailability at molecular level. Various nanoparticle (NPs) formulations of PLA and PLGA loaded with CLH were prepared by solvent evaporation method varying drug: polymer concentration (1:20, 1:10 and 1:5) and characterised (size, encapsulation efficiency, drug loading, scanning electron microscope, differential scanning calorimetry [DSC] and Fourier transform infrared [FTIR] studies). The ratio 1:10 was found to be optimal for a monodispersed and stable nano formulation for both the polymers. NP formulations demonstrated a significant controlled release profile extended up to 144 h (both CLH-PLA and CLH-PLGA). The thermal behaviour (DSC) studies confirmed the molecular dispersion of the drug within the system. The FTIR studies revealed the intactness as well as unaltered structure of drug. The CLH-PLA NPs showed enhanced antimicrobial activity against two pathogenic bacteria Streptococcus faecalis and Bacillus cereus. The results notably suggest that encapsulation of CLH into PLA/PLGA significantly increases the bioavailability of the drug and due to this enhanced drug activity; it can be widely applied for number of therapies. PMID:27463797

  18. Biodegradable PLA (polylactic acid) hinged trays keep quality of fresh-cut and cooked spinach.

    PubMed

    Botondi, Rinaldo; Bartoloni, Serena; Baccelloni, Simone; Mencarelli, Fabio

    2015-09-01

    This work examines the effects of packaging using two different polymeric trays with hinged lids, polyethylene terephthalate (PET) and polylactic acid (PLA), on fresh-cut and cooked spinach (Spinacia oleracea). Samples were stored in a cold room for 16 days at 4 °C. Chemical (total pigments, total polyphenols, ascorbic acid, antioxidant activity), physical (water activity), technological (colour evaluation), sensorial (aroma, visual appearance and water accumulation) and microbial (total aerobic mesophilic and psychrotrophic counts) parameters were tested. Both polymeric trays maintained the overall quality of fresh spinach for 6 days but spinach stored in PLA trays maintained its flavour longer. A significant increase in total polyphenols, antiradical activity, total carotenoids as well as a decrease in ascorbic acid in fresh spinach was observed in the first 3 days of storage in both samples. Unfortunately, the PLA package accumulated condensed water. The total microbial load of fresh-cut spinach reached about 6.3-7.3 log CFU g(-1) within 8 days. Cooked spinach packed in PLA and PET polymeric hinged trays showed the same behaviour as fresh spinach in terms of quality and shelf life. In conclusion, PLA plastic hinged trays can be used for packaging fresh-cut and cooked cut spinach, but the problem of condensed water must be solved.

  19. Snake Venom PLA2s Inhibitors Isolated from Brazilian Plants: Synthetic and Natural Molecules

    PubMed Central

    Carvalho, B. M. A.; Santos, J. D. L.; Xavier, B. M.; Almeida, J. R.; Resende, L. M.; Martins, W.; Marcussi, S.; Marangoni, S.; Stábeli, R. G.; Calderon, L. A.; Soares, A. M.; Da Silva, S. L.; Marchi-Salvador, D. P.

    2013-01-01

    Ophidian envenomation is an important health problem in Brazil and other South American countries. In folk medicine, especially in developing countries, several vegetal species are employed for the treatment of snakebites in communities that lack prompt access to serum therapy. However, the identification and characterization of the effects of several new plants or their isolated compounds, which are able to inhibit the activities of snake venom, are extremely important and such studies are imperative. Snake venom contains several organic and inorganic compounds; phospholipases A2 (PLA2s) are one of the principal toxic components of venom. PLA2s display a wide variety of pharmacological activities, such as neurotoxicity, myotoxicity, cardiotoxicity, anticoagulant, hemorrhagic, and edema-inducing effects. PLA2 inhibition is of pharmacological and therapeutic interests as these enzymes are involved in several inflammatory diseases. This review describes the results of several studies of plant extracts and their isolated active principles, when used against crude snake venoms or their toxic fractions. Isolated inhibitors, such as steroids, terpenoids, and phenolic compounds, are able to inhibit PLA2s from different snake venoms. The design of specific inhibitors of PLA2s might help in the development of new pharmaceutical drugs, more specific antivenom, or even as alternative approaches for treating snakebites. PMID:24171158

  20. Snake venom PLA2s inhibitors isolated from Brazilian plants: synthetic and natural molecules.

    PubMed

    Carvalho, B M A; Santos, J D L; Xavier, B M; Almeida, J R; Resende, L M; Martins, W; Marcussi, S; Marangoni, S; Stábeli, R G; Calderon, L A; Soares, A M; Da Silva, S L; Marchi-Salvador, D P

    2013-01-01

    Ophidian envenomation is an important health problem in Brazil and other South American countries. In folk medicine, especially in developing countries, several vegetal species are employed for the treatment of snakebites in communities that lack prompt access to serum therapy. However, the identification and characterization of the effects of several new plants or their isolated compounds, which are able to inhibit the activities of snake venom, are extremely important and such studies are imperative. Snake venom contains several organic and inorganic compounds; phospholipases A2 (PLA2s) are one of the principal toxic components of venom. PLA2s display a wide variety of pharmacological activities, such as neurotoxicity, myotoxicity, cardiotoxicity, anticoagulant, hemorrhagic, and edema-inducing effects. PLA2 inhibition is of pharmacological and therapeutic interests as these enzymes are involved in several inflammatory diseases. This review describes the results of several studies of plant extracts and their isolated active principles, when used against crude snake venoms or their toxic fractions. Isolated inhibitors, such as steroids, terpenoids, and phenolic compounds, are able to inhibit PLA2s from different snake venoms. The design of specific inhibitors of PLA2s might help in the development of new pharmaceutical drugs, more specific antivenom, or even as alternative approaches for treating snakebites.

  1. Enhanced efficacy of clindamycin hydrochloride encapsulated in PLA/PLGA based nanoparticle system for oral delivery.

    PubMed

    Rauta, Pradipta Ranjan; Das, Niladri Mohan; Nayak, Debasis; Ashe, Sarbani; Nayak, Bismita

    2016-08-01

    Clindamycin hydrochloride (CLH) is a clinically important oral antibiotic with wide spectrum of antimicrobial activity that includes gram-positive aerobes (staphylococci, streptococci etc.), most anaerobic bacteria, Chlamydia and certain protozoa. The current study was focused to develop a stabilised clindamycin encapsulated poly lactic acid (PLA)/poly (D,L-lactide-co-glycolide) (PLGA) nano-formulation with better drug bioavailability at molecular level. Various nanoparticle (NPs) formulations of PLA and PLGA loaded with CLH were prepared by solvent evaporation method varying drug: polymer concentration (1:20, 1:10 and 1:5) and characterised (size, encapsulation efficiency, drug loading, scanning electron microscope, differential scanning calorimetry [DSC] and Fourier transform infrared [FTIR] studies). The ratio 1:10 was found to be optimal for a monodispersed and stable nano formulation for both the polymers. NP formulations demonstrated a significant controlled release profile extended up to 144 h (both CLH-PLA and CLH-PLGA). The thermal behaviour (DSC) studies confirmed the molecular dispersion of the drug within the system. The FTIR studies revealed the intactness as well as unaltered structure of drug. The CLH-PLA NPs showed enhanced antimicrobial activity against two pathogenic bacteria Streptococcus faecalis and Bacillus cereus. The results notably suggest that encapsulation of CLH into PLA/PLGA significantly increases the bioavailability of the drug and due to this enhanced drug activity; it can be widely applied for number of therapies.

  2. Anti-PLA2R Antibodies in Chinese Patients with Membranous Nephropathy.

    PubMed

    Li, Xin; Wei, Dong; Zhou, Zhanmei; Wang, Baoguo; Xu, Ya; Pan, Jie; Yang, Chunli; Lu, Jie; Qiu, Yurong

    2016-01-01

    BACKROUND ~This study used two standardized methods to evaluate anti-PLA2R antibody in serum of primary membranous nephropathy (PMN) among Chinese patients to determine  Anti-PLA2R antibody distribution and whether immunological reactivity reflected by antibody titer correlates with kidney function parameters. MATERIAL AND METHOD ~Overall, 82 subjects with biopsy-proven primary membranous nephropathy (PMN) , 22 cases with secondary membranous nephropathy (SMN), 40 non-MN patients with established glomerulonephritis, 20 healthy volunteers were recruited from the Division of Nephrology, Nanfang Hospital, China. Anti-PLA2R antibody in the serum of each patient was evaluated by both recombinant cell-based indirect immunofluorescence assay (RC-IFA) and enzyme linked immunosorbent assay (ELISA). Kidney function was assessed by proteinuria for 24 hours, serum albumin, blood urea nitrogen (BUN), serum creatine, serum cystatin C. We assessed the correlation between anti-PLA2R antibody levels and clinical parameter in the PMN patients. RESULTS ~ Fifty-three patients with PMN (64.6%) were positive for anti-PLA2R antibody. The level of antibody determined by RC-IFA ranged from 1:10 to 1:1000 and 0 to 1423 RU/ml by ELISA. The two anti-PLA2R test systems correlated very well with each other and reached an agreement of 95.7% for PMN patients. The level of antibody detected by ELISA in patients with PMN also significantly correlated with proteinuria and nephritic-range proteinuria (> 3.5g/day) . CONCLUSIONS ~Anti-PLA2R antibody is sensitive and extremely specific for diagnosis of Chinese patients with primary membranous nephropathy. Concentration of autoantibody against PLA2R is an ideal marker for monitoring the activity of immunological disease.

  3. Expression, purification and refolding of active durum wheat (Triticum durum Desf.) secretory phospholipase A2 from inclusion bodies of Escherichia coli.

    PubMed

    Verlotta, Angelo; Trono, Daniela

    2014-09-01

    Recently, a durum wheat (Triticum durum Desf.) secretory phospholipase A2 (TdsPLA2III) was identified in leaves as potentially involved in plant responses to conditions of limiting water supply. Therefore, to allow future functional studies on TdsPLA2III and shed further light on the involvement of sPLA2 isoforms in specific plant functions, here we report a protocol for the overexpression of TdsPLA2III in Escherichia coli in the form of inclusion bodies, and for its purification and refolding. The use of the Gateway system (Invitrogen) allows the expression of a large quantity of the mature form (without the signal peptide) of TdsPLA2III with an N-terminal 6×His-tag, for purification using Ni-affinity chromatography. The purified recombinant 6×His-TdsPLA2III fusion protein is then refolded using a step-wise dialysis approach. About 40mg purified and active protein was obtained from 1L of cell culture. This recombinant 6×His-TdsPLA2III protein shows PLA2 activity, as it can hydrolyze linoleate from the sn-2 position of 1-palmitoyl-2-linoleoyl-sn-glycero-3-phosphocholine. Moreover, it has some features that are typical of other known plant sPLA2s: Ca(2+)-dependence, inhibition by the disulfide bond reducing agent dithiothreitol, and resistance to high temperature.

  4. Active packaging with antifungal activities.

    PubMed

    Nguyen Van Long, N; Joly, Catherine; Dantigny, Philippe

    2016-03-01

    There have been many reviews concerned with antimicrobial food packaging, and with the use of antifungal compounds, but none provided an exhaustive picture of the applications of active packaging to control fungal spoilage. Very recently, many studies have been done in these fields, therefore it is timely to review this topic. This article examines the effects of essential oils, preservatives, natural products, chemical fungicides, nanoparticles coated to different films, and chitosan in vitro on the growth of moulds, but also in vivo on the mould free shelf-life of bread, cheese, and fresh fruits and vegetables. A short section is also dedicated to yeasts. All the applications are described from a microbiological point of view, and these were sorted depending on the name of the species. Methods and results obtained are discussed. Essential oils and preservatives were ranked by increased efficacy on mould growth. For all the tested molecules, Penicillium species were shown more sensitive than Aspergillus species. However, comparison between the results was difficult because it appeared that the efficiency of active packaging depended greatly on the environmental factors of food such as water activity, pH, temperature, NaCl concentration, the nature, the size, and the mode of application of the films, in addition to the fact that the amount of released antifungal compounds was not constant with time.

  5. Active packaging with antifungal activities.

    PubMed

    Nguyen Van Long, N; Joly, Catherine; Dantigny, Philippe

    2016-03-01

    There have been many reviews concerned with antimicrobial food packaging, and with the use of antifungal compounds, but none provided an exhaustive picture of the applications of active packaging to control fungal spoilage. Very recently, many studies have been done in these fields, therefore it is timely to review this topic. This article examines the effects of essential oils, preservatives, natural products, chemical fungicides, nanoparticles coated to different films, and chitosan in vitro on the growth of moulds, but also in vivo on the mould free shelf-life of bread, cheese, and fresh fruits and vegetables. A short section is also dedicated to yeasts. All the applications are described from a microbiological point of view, and these were sorted depending on the name of the species. Methods and results obtained are discussed. Essential oils and preservatives were ranked by increased efficacy on mould growth. For all the tested molecules, Penicillium species were shown more sensitive than Aspergillus species. However, comparison between the results was difficult because it appeared that the efficiency of active packaging depended greatly on the environmental factors of food such as water activity, pH, temperature, NaCl concentration, the nature, the size, and the mode of application of the films, in addition to the fact that the amount of released antifungal compounds was not constant with time. PMID:26803804

  6. Tryptase Activation of Immortalized Human Urothelial Cell Mitogen-Activated Protein Kinase

    PubMed Central

    Marentette, John O.; Hauser, Paul J.; Hurst, Robert E.; Klumpp, David J.; Rickard, Alice; McHowat, Jane

    2013-01-01

    The pathogenesis of interstitial cystitis/painful bladder syndrome (IC/PBS) is multifactorial, but likely involves urothelial cell dysfunction and mast cell accumulation in the bladder wall. Activated mast cells in the bladder wall release several inflammatory mediators, including histamine and tryptase. We determined whether mitogen-activated protein (MAP) kinases are activated in response to tryptase stimulation of urothelial cells derived from human normal and IC/PBS bladders. Tryptase stimulation of normal urothelial cells resulted in a 2.5-fold increase in extracellular signal regulated kinase 1/2 (ERK 1/2). A 5.5-fold increase in ERK 1/2 activity was observed in urothelial cells isolated from IC/PBS bladders. No significant change in p38 MAP kinase was observed in tryptase-stimulated normal urothelial cells but a 2.5-fold increase was observed in cells isolated from IC/PBS bladders. Inhibition of ERK 1/2 with PD98059 or inhibition of p38 MAP kinase with SB203580 did not block tryptase-stimulated iPLA2 activation. Incubation with the membrane phospholipid-derived PLA2 hydrolysis product lysoplasmenylcholine increased ERK 1/2 activity, suggesting the iPLA2 activation is upstream of ERK 1/2. Real time measurements of impedance to evaluate wound healing of cell cultures indicated increased healing rates in normal and IC/PBS urothelial cells in the presence of tryptase, with inhibition of ERK 1/2 significantly decreasing the wound healing rate of IC/PBS urothelium. We conclude that activation of ERK 1/2 in response to tryptase stimulation may facilitate wound healing or cell motility in areas of inflammation in the bladder associated with IC/PBS. PMID:23922867

  7. Encapsulation of gallic acid/cyclodextrin inclusion complex in electrospun polylactic acid nanofibers: Release behavior and antioxidant activity of gallic acid.

    PubMed

    Aytac, Zeynep; Kusku, Semran Ipek; Durgun, Engin; Uyar, Tamer

    2016-06-01

    Cyclodextrin-inclusion complexes (CD-ICs) possess great prominence in food and pharmaceutical industries due to their enhanced ability for stabilization of active compounds during processing, storage and usage. Here, CD-IC of gallic acid (GA) with hydroxypropyl-beta-cyclodextrin (GA/HPβCD-IC) was prepared and then incorporated into polylactic acid (PLA) nanofibers (PLA/GA/HPβCD-IC-NF) using electrospinning technique to observe the effect of CD-ICs in the release behavior of GA into three different mediums (water, 10% ethanol and 95% ethanol). The GA incorporated PLA nanofibers (PLA/GA-NFs) were served as control. Phase solubility studies showed an enhanced solubility of GA with increasing amount of HPβCD. The detailed characterization techniques (XRD, TGA and (1)H-NMR) confirmed the formation of inclusion complex between GA and HPβCD. Computational modeling studies indicated that the GA made an efficient complex with HPβCD at 1:1 either in vacuum or aqueous system. SEM images revealed the bead-free and uniform morphology of PLA/GA/HPβCD-IC-NF. The release studies of GA from PLA/GA/HPβCD-IC-NF and PLA/GA-NF were carried out in water, 10% ethanol and 95% ethanol, and the findings revealed that PLA/GA/HPβCD-IC-NF has released much more amount of GA in water and 10% ethanol system when compared to PLA/GA-NF. In addition, GA was released slowly from PLA/GA/HPβCD-IC-NF into 95% ethanol when compared to PLA/GA-NF. It was also observed that electrospinning process had no negative effect on the antioxidant activity of GA when GA was incorporated in PLA nanofibers.

  8. Encapsulation of gallic acid/cyclodextrin inclusion complex in electrospun polylactic acid nanofibers: Release behavior and antioxidant activity of gallic acid.

    PubMed

    Aytac, Zeynep; Kusku, Semran Ipek; Durgun, Engin; Uyar, Tamer

    2016-06-01

    Cyclodextrin-inclusion complexes (CD-ICs) possess great prominence in food and pharmaceutical industries due to their enhanced ability for stabilization of active compounds during processing, storage and usage. Here, CD-IC of gallic acid (GA) with hydroxypropyl-beta-cyclodextrin (GA/HPβCD-IC) was prepared and then incorporated into polylactic acid (PLA) nanofibers (PLA/GA/HPβCD-IC-NF) using electrospinning technique to observe the effect of CD-ICs in the release behavior of GA into three different mediums (water, 10% ethanol and 95% ethanol). The GA incorporated PLA nanofibers (PLA/GA-NFs) were served as control. Phase solubility studies showed an enhanced solubility of GA with increasing amount of HPβCD. The detailed characterization techniques (XRD, TGA and (1)H-NMR) confirmed the formation of inclusion complex between GA and HPβCD. Computational modeling studies indicated that the GA made an efficient complex with HPβCD at 1:1 either in vacuum or aqueous system. SEM images revealed the bead-free and uniform morphology of PLA/GA/HPβCD-IC-NF. The release studies of GA from PLA/GA/HPβCD-IC-NF and PLA/GA-NF were carried out in water, 10% ethanol and 95% ethanol, and the findings revealed that PLA/GA/HPβCD-IC-NF has released much more amount of GA in water and 10% ethanol system when compared to PLA/GA-NF. In addition, GA was released slowly from PLA/GA/HPβCD-IC-NF into 95% ethanol when compared to PLA/GA-NF. It was also observed that electrospinning process had no negative effect on the antioxidant activity of GA when GA was incorporated in PLA nanofibers. PMID:27040215

  9. Active tectonics

    SciTech Connect

    Not Available

    1986-01-01

    This study is part of a series of Studies in Geophysics that have been undertaken for the Geophysics Research Forum by the Geophysics Study Committee. One purpose of each study is to provide assessments from the scientific community to aid policymakers in decisions on societal problems that involve geophysics. An important part of such assessments is an evaluation of the adequacy of current geophysical knowledge and the appropriateness of current research programs as a source of information required for those decisions. The study addresses our current scientific understanding of active tectonics --- particularly the patterns and rates of ongoing tectonic processes. Many of these processes cannot be described reasonably using the limited instrumental or historical records; however, most can be described adequately for practical purposes using the geologic record of the past 500,000 years. A program of fundamental research focusing especially on Quaternary tectonic geology and geomorphology, paleoseismology, neotectonics, and geodesy is recommended to better understand ongoing, active tectonic processes. This volume contains 16 papers. Individual papers are indexed separately on the Energy Database.

  10. Angiotensin II-induced Akt activation through the epidermal growth factor receptor in vascular smooth muscle cells is mediated by phospholipid metabolites derived by activation of phospholipase D.

    PubMed

    Li, Fang; Malik, Kafait U

    2005-03-01

    Angiotensin II (Ang II) activates cytosolic Ca(2+)-dependent phospholipase A(2) (cPLA(2)), phospholipase D (PLD), p38 mitogen-activated protein kinase (MAPK), epidermal growth factor receptor (EGFR) and Akt in vascular smooth muscle cells (VSMC). This study was conducted to investigate the relationship between Akt activation by Ang II and other signaling molecules in rat VSMC. Ang II-induced Akt phosphorylation was significantly reduced by the PLD inhibitor 1-butanol, but not by its inactive analog 2-butanol, and by brefeldin A, an inhibitor of the PLD cofactor ADP-ribosylation factor, and in cells infected with retrovirus containing PLD(2) siRNA or transfected with PLD(2) antisense but not control LacZ or sense oligonucleotide. Diacylglycerol kinase inhibitor II diminished Ang II-induced and diC8-phosphatidic acid (PA)-increased Akt phosphorylation, suggesting that PLD-dependent Akt activation is mediated by PA. Ang II-induced EGFR phosphorylation was inhibited by 1-butanol and PLD(2) siRNA and also by cPLA(2) siRNA. In addition, the inhibitor of arachidonic acid (AA) metabolism 5,8,11,14-eicosatetraynoic acid (ETYA) reduced both Ang II- and AA-induced EGFR transactivation. Furthermore, ETYA, cPLA(2) antisense, and cPLA(2) siRNA attenuated Ang II-elicited PLD activation. p38 MAPK inhibitor SB202190 [4-(4-flurophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)1H-imidazole] reduced PLD activity and EGFR and Akt phosphorylation elicited by Ang II. Pyrrolidine-1, a cPLA(2) inhibitor, and cPLA(2) siRNA decreased p38 MAPK activity. These data indicate that Ang II-stimulated Akt activity is mediated by cPLA(2)-dependent, p38 MAPK regulated PLD(2) activation and EGFR transactivation. We propose the following scheme of the sequence of events leading to activation of Akt in VSMC by Ang II: Ang II-->cPLA(2)-->AA-->p38 MAPK-->PLD(2)-->PA-->EGFR-->Akt. PMID:15525798

  11. Angiotensin II-induced Akt activation through the epidermal growth factor receptor in vascular smooth muscle cells is mediated by phospholipid metabolites derived by activation of phospholipase D.

    PubMed

    Li, Fang; Malik, Kafait U

    2005-03-01

    Angiotensin II (Ang II) activates cytosolic Ca(2+)-dependent phospholipase A(2) (cPLA(2)), phospholipase D (PLD), p38 mitogen-activated protein kinase (MAPK), epidermal growth factor receptor (EGFR) and Akt in vascular smooth muscle cells (VSMC). This study was conducted to investigate the relationship between Akt activation by Ang II and other signaling molecules in rat VSMC. Ang II-induced Akt phosphorylation was significantly reduced by the PLD inhibitor 1-butanol, but not by its inactive analog 2-butanol, and by brefeldin A, an inhibitor of the PLD cofactor ADP-ribosylation factor, and in cells infected with retrovirus containing PLD(2) siRNA or transfected with PLD(2) antisense but not control LacZ or sense oligonucleotide. Diacylglycerol kinase inhibitor II diminished Ang II-induced and diC8-phosphatidic acid (PA)-increased Akt phosphorylation, suggesting that PLD-dependent Akt activation is mediated by PA. Ang II-induced EGFR phosphorylation was inhibited by 1-butanol and PLD(2) siRNA and also by cPLA(2) siRNA. In addition, the inhibitor of arachidonic acid (AA) metabolism 5,8,11,14-eicosatetraynoic acid (ETYA) reduced both Ang II- and AA-induced EGFR transactivation. Furthermore, ETYA, cPLA(2) antisense, and cPLA(2) siRNA attenuated Ang II-elicited PLD activation. p38 MAPK inhibitor SB202190 [4-(4-flurophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)1H-imidazole] reduced PLD activity and EGFR and Akt phosphorylation elicited by Ang II. Pyrrolidine-1, a cPLA(2) inhibitor, and cPLA(2) siRNA decreased p38 MAPK activity. These data indicate that Ang II-stimulated Akt activity is mediated by cPLA(2)-dependent, p38 MAPK regulated PLD(2) activation and EGFR transactivation. We propose the following scheme of the sequence of events leading to activation of Akt in VSMC by Ang II: Ang II-->cPLA(2)-->AA-->p38 MAPK-->PLD(2)-->PA-->EGFR-->Akt.

  12. Curcumin-Loaded PLA Nanoparticles: Formulation and Physical Evaluation

    PubMed Central

    Rachmawati, Heni; Yanda, Yulia L.; Rahma, Annisa; Mase, Nobuyuki

    2016-01-01

    Curcumin is a polyphenolic compound derived from Curcuma domestica (Zingiberaceae) that possesses diverse pharmacological effects including anti-inflammatory, antioxidant, antimicrobial, and anticarcinogenic activities. Although phase I clinical trials have shown curcumin as a safe drug even at high doses (12 g/day) in humans, poor bioavaibility largely limits its pharmacological activity. Nanoencapsulation in biodegradable polymers is a promising alternative to improve curcumin bioavaibility. In this study, curcumin was encapsulated in biodegradable polymer poly-(lactic acid) (PLA) nanoparticles via the emulsification-solvent evaporation method. Optimization of selected parameters of this method including the type of solvent, surfactant concentration, drug loading, sonication time, and centrifugation speed, were performed to obtain polymeric nano-carriers with optimum characteristics. Dichloromethane was used as the solvent and vitamin E polyethylene glycol succinate (TPGS) was used as the surfactant. Four minutes of sonication time and centrifugation at 10500 rpm were able to produce spherical nanoparticles with average size below 300 nm. The highest encapsulation efficiency was found on PLA nanoparticles containing 5% of curcumin at 89.42 ± 1.04%. The particle size, polydispersity index, zeta potential of 5% curcumin-PLA nanoparticles were 387.50 ± 58.60 nm, 0.289 ± 0.047, and −1.12 mV, respectively. Differential Scanning Calorimetry (DSC) and X-Ray Diffraction (XRD) studies showed partial interaction between the drug and polymer. PMID:27110509

  13. Preliminary X-ray crystallographic studies of BthTX-II, a myotoxic Asp49-phospholipase A{sub 2} with low catalytic activity from Bothrops jararacussu venom

    SciTech Connect

    Corrêa, L. C.; Marchi-Salvador, D. P.; Cintra, A. C. O.; Soares, A. M.

    2006-08-01

    A myotoxic Asp49-PLA{sub 2} with low catalytic activity from B. jararacussu (BthTX-II) was crystallized in the monoclinic crystal system; a complete X-ray diffraction data set was collected and a molecular-replacement solution was obtained. The oligomeric structure of BthTX-II resembles those of the Asp49-PLA{sub 2} PrTX-III and all bothropic Lys49-PLA{sub 2}s. For the first time, a complete X-ray diffraction data set has been collected from a myotoxic Asp49-phospholipase A{sub 2} (Asp49-PLA{sub 2}) with low catalytic activity (BthTX-II from Bothrops jararacussu venom) and a molecular-replacement solution has been obtained with a dimer in the asymmetric unit. The quaternary structure of BthTX-II resembles the myotoxin Asp49-PLA{sub 2} PrTX-III (piratoxin III from B. pirajai venom) and all non-catalytic and myotoxic dimeric Lys49-PLA{sub 2}s. In contrast, the oligomeric structure of BthTX-II is different from the highly catalytic and non-myotoxic BthA-I (acidic PLA{sub 2} from B. jararacussu). Thus, comparison between these structures should add insight into the catalytic and myotoxic activities of bothropic PLA{sub 2}s.

  14. DAVIC activities

    NASA Astrophysics Data System (ADS)

    Fujiwara, Hiroshi

    1995-12-01

    DAVIC (Digital Audio Visual Council) is the defacto standardization organization established in Mar. 1994, based on international consensus for digital audio visual services. After completion of MPEG2 standardization, the broadcasting industry, the communication industry, the computer industry, and consumer electronics industry have started development of concrete services and products. Especially the interactive digital audio visual services, such as Video On Demand (VOD) or Near Video On Demand (NVOD), have become hot topics all over the world. Such interactive digital audio visual services are combined technologies of multi-media coding, digital transmission and computer networking. Therefore more than 150 organizations from all industry sectors have participated in DAVIC and are contributing from their own industrial contexts. DAVIC's basic policy is to use the available technologies specified by the other standards bodies as much as possible. So DAVIC's standardization activities have close relationship with ISO IEC/JTC1/SC29, ITU-T SG 9, ATM-Forum, IETF, IMA, DVB, etc. DAVIC is trying to specify Applications, Reference Models, Security, Usage Information Control, and the interfaces and protocols among the Content Provider, the Server, the core network, the access network, and the Set Top Unit. DAVIC's first goal is to specify DAVIC1.0 based on CFP1 (Call for Proposal) and CFP2 by Dec. 1995, and the next direction is under preparation for further progress based on CFP3 and CFP4.

  15. The existence of phospholipase A(2) activity in plant mitochondria and its activation by hyperosmotic stress in durum wheat (Triticum durum Desf.).

    PubMed

    Trono, Daniela; Soccio, Mario; Laus, Maura N; Pastore, Donato

    2013-02-01

    The activity of mitochondrial phospholipase A(2) (PLA(2)) was shown for the first time in plants. It was observed in etiolated seedlings from durum wheat, barley, tomato, spelt and green seedlings of maize, but not in potato and topinambur tubers and lentil etiolated seedlings. This result was achieved by a novel spectrophotometric assay based on the coupled PLA(2)/lipoxygenase reactions using 1-palmitoyl-2-linoleoyl-sn-glycero-3-phosphatidylcholine as substrate; the mitochondrial localisation was assessed by checking recovery of marker enzymes. Durum wheat mitochondrial PLA(2) (DWM-PLA(2)) showed maximal activity at pH 9.0 and 1mM Ca(2+), hyperbolic kinetics (K(m)=90±6μM, V(max)=29±1nmolmin(-1)mg(-1) of protein) and inhibition by methyl arachidonyl fluorophosphonate, 5-(4-benzyloxyphenyl)-4S-(7-phenylheptanoylamino)pentanoic acid and palmityl trifluoromethyl ketone. Reactive oxygen species had no effect on DWM-PLA(2), that instead was activated by about 50% and 95%, respectively, under salt (0.21M NaCl) and osmotic (0.42M mannitol) stress imposed during germination. Contrarily, a secondary Ca(2+)-independent activity, having optimum at pH 7.0, was stress-insensitive. We propose that the activation of DWM-PLA(2) is responsible for the strong increase of free fatty acids recently measured in mitochondria under the same stress conditions [Laus, et al., J. Exp. Bot. 62 (2011) 141-154] that, in turn, activate potassium channel and uncoupling protein, able to counteract hyperosmotic stress.

  16. Continuous cellularization of calcium phosphate hybrid scaffolds induced by plasma polymer activation.

    PubMed

    Bergemann, Claudia; Cornelsen, Matthias; Quade, Antje; Laube, Thorsten; Schnabelrauch, Matthias; Rebl, Henrike; Weißmann, Volker; Seitz, Hermann; Nebe, Barbara

    2016-02-01

    The generation of hybrid materials based on β-tricalcium phosphate (TCP) and various biodegradable polymers like poly(l-lactide-co-d,l-lactide) (PLA) represents a common approach to overcoming the disadvantages of pure TCP devices. These disadvantages lie in TCP's mechanical properties, such as brittleness. The positive characteristic of PLA - improvement of compressive strength of calcium phosphate scaffolds - is diametrically opposed to its cell attractiveness. Therefore, the objective of this work was to optimize osteoblast migration and cellularization inside a three-dimensionally (3D) printed, PLA polymer stabilized TCP hybrid scaffold by a plasma polymer process depositing amino groups via allylamine. MG-63 osteoblastic cells inside the 10mm hybrid scaffold were dynamically cultivated for 14days in a 3D model system integrated in a perfusion reactor. The whole TCP/PLA hybrid scaffold was continuously colonized due to plasma polymerized allylamine activation inducing the migration potential of osteoblasts.

  17. Continuous cellularization of calcium phosphate hybrid scaffolds induced by plasma polymer activation.

    PubMed

    Bergemann, Claudia; Cornelsen, Matthias; Quade, Antje; Laube, Thorsten; Schnabelrauch, Matthias; Rebl, Henrike; Weißmann, Volker; Seitz, Hermann; Nebe, Barbara

    2016-02-01

    The generation of hybrid materials based on β-tricalcium phosphate (TCP) and various biodegradable polymers like poly(l-lactide-co-d,l-lactide) (PLA) represents a common approach to overcoming the disadvantages of pure TCP devices. These disadvantages lie in TCP's mechanical properties, such as brittleness. The positive characteristic of PLA - improvement of compressive strength of calcium phosphate scaffolds - is diametrically opposed to its cell attractiveness. Therefore, the objective of this work was to optimize osteoblast migration and cellularization inside a three-dimensionally (3D) printed, PLA polymer stabilized TCP hybrid scaffold by a plasma polymer process depositing amino groups via allylamine. MG-63 osteoblastic cells inside the 10mm hybrid scaffold were dynamically cultivated for 14days in a 3D model system integrated in a perfusion reactor. The whole TCP/PLA hybrid scaffold was continuously colonized due to plasma polymerized allylamine activation inducing the migration potential of osteoblasts. PMID:26652403

  18. Participation of the Na+/H+ exchanger in the phospholipase-A2 activation of luteinizing hormone-releasing hormone release in rat hypothalamic fragments.

    PubMed

    Nava, L E; Tinajero, J C; Malacara, J M

    1992-01-01

    The role of the Na+/H+ exchanger in the phospholipase-A2 (PLA2) stimulation of LHRH release was investigated using in vitro incubations of rat hypothalamic fragments. It was found that monensin, the Na+/H+ ionophore, increased LHRH release in a dose-related manner. That effect diminished in the absence of calcium as well as after the addition of 2,4'-dibromoacetophenone, a blocker of PLA2 action. Amiloride, a blocker of the Na+/H+ exchanger, did not alter the effect of monensin. However, amiloride significantly diminished the effect of melittin, an activator of PLA2 action. LHRH release under PLA2 did not change when amiloride was added to the incubation medium. Lysophosphatidylcholine also increased LHRH release. These results were interpreted as evidence of the participation of Na+/H+ exchange in PLA2 activation in the release of LHRH in rat hypothalamic fragments. A role of lysophospholipids in this process is also suggested.

  19. Inherited human cPLA2α deficiency is associated with impaired eicosanoid biosynthesis, small intestinal ulceration, and platelet dysfunction

    PubMed Central

    Adler, David H.; Cogan, Joy D.; Phillips, John A.; Schnetz-Boutaud, Nathalie; Milne, Ginger L.; Iverson, Tina; Stein, Jeffrey A.; Brenner, David A.; Morrow, Jason D.; Boutaud, Olivier; Oates, John A.

    2008-01-01

    Cytosolic phospholipase A2α (cPLA2α) hydrolyzes arachidonic acid from cellular membrane phospholipids, thereby providing enzymatic substrates for the synthesis of eicosanoids, such as prostaglandins and leukotrienes. Considerable understanding of cPLA2α function has been derived from investigations of the enzyme and from cPLA2α-null mice, but knowledge of discrete roles for this enzyme in humans is limited. We investigated a patient hypothesized to have an inherited prostanoid biosynthesis deficiency due to his multiple, complicated small intestinal ulcers despite no use of cyclooxygenase inhibitors. Levels of thromboxane B2 and 12-hydroxyeicosatetraenoic acid produced by platelets and leukotriene B4 released from calcium ionophore–activated blood were markedly reduced, indicating defective enzymatic release of the arachidonic acid substrate for the corresponding cyclooxygenase and lipoxygenases. Platelet aggregation and degranulation induced by adenosine diphosphate or collagen were diminished but were normal in response to arachidonic acid. Two heterozygous single base pair mutations and a known SNP were found in the coding regions of the patient’s cPLA2α genes (p.[Ser111Pro]+[Arg485His; Lys651Arg]). The total PLA2 activity in sonicated platelets was diminished, and the urinary metabolites of prostacyclin, prostaglandin E2, prostaglandin D2, and thromboxane A2 were also reduced. These findings characterize what we believe is a novel inherited deficiency of cPLA2. PMID:18451993

  20. Active knee joint flexibility and sports activity.

    PubMed

    Hahn, T; Foldspang, A; Vestergaard, E; Ingemann-Hansen, T

    1999-04-01

    The aim of the study was to estimate active knee flexion and active knee extension in athletes and to investigate the potential association of each to different types of sports activity. Active knee extension and active knee flexion was measured in 339 athletes. Active knee extension was significantly higher in women than in men and significantly positively associated with weekly hours of swimming and weekly hours of competitive gymnastics. Active knee flexion was significantly positively associated with participation in basketball, and significantly negatively associated with age and weekly hours of soccer, European team handball and swimming. The results point to sport-specific adaptation of active knee flexion and active knee extension.

  1. IASS Activity

    NASA Astrophysics Data System (ADS)

    Hojaev, Alisher S.; Ibragimova, Elvira M.

    2015-08-01

    It’s well known, astronomy in Uzbekistan has ancient roots and traditions (e.g., Mirzo Ulugh Beg, Abū al-Rayhān al-Bīrūnī, Abū ‘Abdallāh al-Khwārizmī) and astronomical heritage carefully preserved. Nowadays uzbek astronomers play a key role in scientific research but also in OAD and Decadal Plan activity in the Central Asia region. International Aerospace School (IASS) is an amazing and wonderful event held annually about 30 years. IASS is unique project in the region, and at the beginning we spent the Summer and Winter Schools. At present in the summer camp we gather about 50 teenage and undergraduate students over the country and abroad (France, Malaysia, Turkey, Azerbaijan, Pakistan, Russia, etc.). They are selected on the basis of tests of astronomy and space issues. During two weeks of IASS camp the invited scientists, cosmonauts and astronauts as well as other specialists give lectures and engage in practical exercises with IASS students in astronomy, including daily observations of the Sun and night sky observations with meniscus telescope, space research and exploration, aerospace modelling, preparation and presentation of original projects. This is important that IASS gives not theoretical grounds only but also practically train the students and the hands-on training is the major aims of IASS. Lectures and practice in the field of astronomy carried out with the direct involvement and generous assistance of Uranoscope Association (Paris, France). The current 26-th IASS is planned to held in July 2015.

  2. Activation Energy

    NASA Technical Reports Server (NTRS)

    Gadeken, Owen

    2002-01-01

    Teaming is so common in today's project management environment that most of us assume it comes naturally. We further assume that when presented with meaningful and challenging work, project teams will naturally engage in productive activity to complete their tasks. This assumption is expressed in the simple (but false) equation: Team + Work = Teamwork. Although this equation appears simple and straightforward, it is far from true for most project organizations whose reality is a complex web of institutional norms based on individual achievement and rewards. This is illustrated by the very first successful team experience from my early Air Force career. As a young lieutenant, I was sent to Squadron Officer School, which was the first in the series of Air Force professional military education courses I was required to complete during my career. We were immediately formed into teams of twelve officers. Much of the course featured competition between these teams. As the most junior member of my team, I quickly observed the tremendous pressure to show individual leadership capability. At one point early in the course, almost everyone in our group was vying to become the team leader. This conflict was so intense that it caused us to fail miserably in our first outdoor team building exercise. We spent so much time fighting over leadership that we were unable to complete any of the events on the outdoor obstacle course. This complete lack of success was so disheartening to me that I gave our team little hope for future success. What followed was a very intense period of bickering, conflict, and even shouting matches as our dysfunctional team tried to cope with our early failures and find some way to succeed. British physician and researcher Wilfred Bion (Experiences in Groups, 1961) discovered that there are powerful psychological forces inherent in all groups that divert from accomplishing their primary tasks. To overcome these restraining forces and use the potential

  3. Thrombin produces phosphorylation of cytosolic phospholipase A2 by a mitogen-activated protein kinase kinase-independent mechanism in the human astrocytoma cell line 1321N1.

    PubMed Central

    Hernández, M; Bayón, Y; Sánchez Crespo, M; Nieto, M L

    1997-01-01

    The release of [3H]arachidonic acid was studied in the 1321N1 astrocytoma cell line upon stimulation with thrombin. The effect of thrombin was antagonized by hirudin only when both compounds were added simultaneously, which suggests activation of thrombin receptor. Evidence that the cytosolic phospholipase A2 (cPLA2) takes part in thrombin-induced arachidonate release was provided by the finding that thrombin induced retardation of the mobility of cPLA2 in SDS/polyacrylamide gels, which is a feature of the activation of cPLA2 by mitogen-activated protein (MAP) kinases. Thrombin induced activation of two members of the MAP kinase family whose consensus primary sequence appears in cPLA2, namely p42-MAP kinase and c-Jun kinase. However, the activation of c-Jun kinase preceded the phosphorylation of cPLA2 more clearly than the activation of p42-MAK kinase did. Both cPLA2 and c-Jun kinase activation were not affected by PD-98059, a specific inhibitor of MAP kinase kinases, which indeed completely blocked p42-MAP kinase shift. Heat shock, a well-known activator of c-Jun kinase, also phosphorylated cPLA2 but not p42-MAP kinase. These data indicate the existence in astrocytoma cells of a signalling pathway triggered by thrombin receptor stimulation that activates a kinase cascade acting on the Pro-Leu-Ser-Pro consensus primary sequence, activates cPLA2, and associates the release of arachidonate with nuclear signalling pathways. PMID:9359863

  4. Anti-PLA2R Antibodies in Chinese Patients with Membranous Nephropathy

    PubMed Central

    Li, Xin; Wei, Dong; Zhou, Zhanmei; Wang, Baoguo; Xu, Ya; Pan, Jie; Yang, Chunli; Lu, Jie; Qiu, Yurong

    2016-01-01

    Background This study used 2 standardized methods to evaluate anti-PLA2R antibody in sera of Chinese patients with primary membranous nephropathy (PMN) and to determine whether immunological reactivity reflected by antibody titer correlates with kidney function parameters. Material/Methods Overall, 82 subjects with biopsy-proven primary membranous nephropathy (PMN), 22 cases with secondary membranous nephropathy (SMN), 40 non-MN patients with established glomerulonephritis, and 20 healthy volunteers were recruited from the Division of Nephrology, Nanfang Hospital, China. Anti-PLA2R antibody in the serum of each patient was evaluated by both recombinant cell-based indirect immunofluorescence assay (RC-IFA) and enzyme-linked immunosorbent assay (ELISA). Kidney function was assessed by proteinuria for 24 hours, serum albumin, blood urea nitrogen (BUN), serum creatine, and serum cystatin C. We assessed the correlation between anti-PLA2R antibody levels and clinical parameters in the PMN patients. Results Fifty-three patients with PMN (64.6%) were positive for anti-PLA2R antibody. The level of antibody determined by RC-IFA ranged from 1: 10 to 1: 1000 and 0 to 1423 RU/ml by ELISA. The 2 anti-PLA2R test systems correlated very well with each other and reached an agreement of 95.7% for PMN patients. The level of antibody detected by ELISA in patients with PMN was also significantly correlated with proteinuria and nephritic-range proteinuria (>3.5 g/day). Conclusions Anti-PLA2R antibody is sensitive and extremely specific for diagnosis of Chinese patients with primary membranous nephropathy. Concentration of autoantibody against PLA2R may be an ideal marker for monitoring the activity of immunological disease. PMID:27179439

  5. Lipoprotein-Associated Phospholipase A2 Activity Predicts Progression of Subclinical Coronary Atherosclerosis

    PubMed Central

    Kinney, Gregory L.; Snell-Bergeon, Janet K.; Maahs, David M.; Eckel, Robert H.; Ehrlich, James; Rewers, Marian

    2011-01-01

    Abstract Background Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a lipoprotein-associated enzyme that cleaves oxidized phosphatidylcholines, generating pro-atherosclerotic lysophosphatidylcholine and oxidized free fatty acids. Lp-PLA2 is independently associated with cardiovascular disease (CVD) in a variety of populations. Coronary calcium is a measure of subclinical CVD, and progression of coronary calcification predicts future CVD events. In type 1 diabetes there is an increase in coronary calcium and CVD despite a favorable lipid profile. Levels of Lp-PLA2 in type 1 diabetes are not known, nor is the relationship between Lp-PLA2 and progression of coronary calcification. Methods The Coronary Artery Calcification in Type 1 Diabetes study measured coronary calcium by electron-beam computed tomography twice over a 2.6 ± 0.3-year interval. Lp-PLA2 mass and activity were measured at baseline (n = 1,097 subjects, 506 with and 591 without type 1 diabetes). Results In type 1 diabetes Lp-PLA2 mass was marginally higher (285 ± 79 vs. 278 ± 78 ng/mL, P = 0.1), and Lp-PLA2 activity was significantly lower (137 ± 30 vs. 146 ± 36 nmol/min/mL, P < 0.0001) than in those without diabetes. There was a greater proportion of those with progression of coronary calcification in type 1 diabetes compared with those without diabetes (24% vs. 10%, P < 0.0001). Lp-PLA2 activity was independently associated with progression of coronary calcification in multivariate analysis (4th quartile verses bottom three quartiles, odds ratio = 1.77 [1.08–2.91], P = 0.02). LpPLA2 mass was not significantly associated with progression of coronary calcification in this cohort (P = 0.09). Conclusions Lp-PLA2 activity predicts progression of subclinical atherosclerosis in individuals with and without type 1 diabetes. PMID:21291330

  6. Interaction of surfactant protein A with peroxiredoxin 6 regulates phospholipase A2 activity.

    PubMed

    Wu, Yong-Zheng; Manevich, Yefim; Baldwin, James L; Dodia, Chandra; Yu, Kevin; Feinstein, Sheldon I; Fisher, Aron B

    2006-03-17

    Peroxiredoxin 6 (Prdx6) is a "moonlighting" protein with both GSH peroxidase and phospholipase A(2) (PLA(2)) activities. This protein is responsible for degradation of internalized dipalmitoylphosphatidylcholine, the major phospholipid component of lung surfactant. The PLA(2) activity is inhibited by surfactant protein A (SP-A). We postulate that SP-A regulates the PLA(2) activity of Prdx6 through direct protein-protein interaction. Recombinant human Prdx6 and SP-A isolated from human alveolar proteinosis fluid were studied. Measurement of kinetic constants at pH 4.0 (maximal PLA(2) activity) showed K(m)0.35 mm and V(max) 138 nmol/min/mg of protein. SP-A inhibited PLA(2) activity non-competitively with K(i) 10 mug/ml and was Ca(2+) -independent. Activity at pH 7.4 was approximately 50% less, and inhibition by SP-A was partially dependent on Ca(2+). Interaction of SP-A and Prdx6 at pH 7.4 was shown by Prdx6-mediated inhibition of SP-A binding to agarose beads, a pull-down assay using His-tagged Prdx6 and Ni(2) -chelating beads, co-immunoprecipitation from lung epithelial cells and from a binary mixture of the two proteins, binding after treatment with a trifunctional cross-linker, and size-exclusion chromatography. Analysis by static light scattering and surface plasmon resonance showed calcium-independent SP-A binding to Prdx6 at pH 4.0 and partial Ca(2+) dependence of binding at pH 7.4. These results indicate a direct interaction between SP-A and Prdx6, which provides a mechanism for regulation of the PLA(2) activity of Prdx6 by SP-A. PMID:16330552

  7. Identification and characterization of phospholipase A/sub 2/ (PLA/sub 2/) in bovine pulmonary endothelial cells (BPEC)

    SciTech Connect

    Martin, T.W.; Wysolmerski, R.B.; Lagunoff, D.

    1986-03-01

    Phosphatidylcholine labeled in the sn-2 position with /sup 3/H-oleic acid was used to measure PLA/sub 2/ in cell sonicates (CS) prepared from confluent cultures of BPEC. Substrate at 10-200 ..mu..M was incubated with 5-30 ..mu..g of CS protein in HEPES buffer at 37/sup 0/C. A plot of /sup 3/H-oleic acid release vs time was linear and proportional to the amount of CS protein. Lineweaver-Burk plots of the data were linear with V/sub max/ = 22.2 nmole/mg protein/hr and K/sub d/ = 121 ..mu..M. Under these conditions, phospholipase C activity was 20-fold lower, and phospholipase A/sub 1/ activity was not detectable. PLA/sub 2/ activity was pH-dependent with optima at 4.5 and 7.5. Ca/sup + +/ was not required for activity, and addition of up to 10 mM Ca/sup + +/ to CS in EDTA increased activity by only 10-20%. After centrifugation of CS at 100,000 g for 90 min, 62% of the PLA/sub 2/ activity was recovered in the particular fraction. Triton X-100 (0.006-0.4%) inhibited PLA/sub 2/ up to 90%, whereas 2 mM deoxycholate produced nearly 3-fold activation. Of several agents tested, bromophenacylbromide (BPB) was the most effective inhibitor. Treatment of CS with BPB at 37/sup 0/C for 30 min produced up to 9% inhibition (K/sub i/ = 5 ..mu..M). Phenylmethanesulfonyl fluoride at 200 ..mu..m produced 41% inhibition. Quinacrine at 1 mM inhibited PLA/sub 2/ by 18%. These data define characteristics of BPEC PLA/sub 2/ that should prove useful in studies of the role of this enzyme in specific cellular functions.

  8. Transferrin modified PEG-PLA-resveratrol conjugates: in vitro and in vivo studies for glioma.

    PubMed

    Guo, Wanhua; Li, Aimei; Jia, Zhijun; Yuan, Yi; Dai, Haifeng; Li, Hongxiu

    2013-10-15

    Glioblastoma is one of the most malignant brain tumors with a poor prognosis. In this study, we examined the effects of transferrin (Tf)-modified poly ethyleneglycol-poly lactic acid (PEG-PLA) nanoparticles conjugated with resveratrol (Tf-PEG-PLA-RSV) to glioma therapy in vitro and in vivo. The cell viability of Tf-PEG-PLA-RSV on C6 and U87 glioma cells was determined by the MTT assay. In vivo biodistribution and antitumor activity were investigated in Brain glioma bearing rat model of C6 glioma by i.p. administration of RSV-polymer conjugates. We found that the average diameter of each Tf-PEG-PLA-RSV is around 150 nm with 32 molecules of Tf on surface. In vitro cytotoxicity of PEG-PLA-RSV against C6 and U87 cells was higher than that of free RSV, and further the modification of Tf enhanced the cytotoxicity of the RSV-polymer conjugates as a result of the increased cellular uptake of the RSV-modified conjugates by glioma cells. In comparison with free RSV, RSV conjugates could significantly decrease tumor volume and accumulate in brain tumor, which resulted in prolonging the survival of C6 glioma-bearing rats. These results suggest that Tf-NP-RSV had a potential of therapeutic effect to glioma both in vitro and in vivo and might be a potential candidate for targeted therapy of glioma and worthy of further investigation.

  9. Impact of the Pla Protease Substrate α2-Antiplasmin on the Progression of Primary Pneumonic Plague

    PubMed Central

    Eddy, Justin L.; Schroeder, Jay A.; Zimbler, Daniel L.; Bellows, Lauren E.

    2015-01-01

    Many pathogens usurp the host hemostatic system during infection to promote pathogenesis. Yersinia pestis, the causative agent of plague, expresses the plasminogen activator protease Pla, which has been shown in vitro to target and cleave multiple proteins within the fibrinolytic pathway, including the plasmin inhibitor α2-antiplasmin (A2AP). It is not known, however, if Pla inactivates A2AP in vivo; the role of A2AP during respiratory Y. pestis infection is not known either. Here, we show that Y. pestis does not appreciably cleave A2AP in a Pla-dependent manner in the lungs during experimental pneumonic plague. Furthermore, following intranasal infection with Y. pestis, A2AP-deficient mice exhibit no difference in survival time, bacterial burden in the lungs, or dissemination from wild-type mice. Instead, we found that in the absence of Pla, A2AP contributes to the control of the pulmonary inflammatory response during infection by reducing neutrophil recruitment and cytokine production, resulting in altered immunopathology of the lungs compared to A2AP-deficient mice. Thus, our data demonstrate that A2AP is not significantly affected by the Pla protease during pneumonic plague, and although A2AP participates in immune modulation in the lungs, it has limited impact on the course or ultimate outcome of the infection. PMID:26438794

  10. Impact of the Pla protease substrate α2-antiplasmin on the progression of primary pneumonic plague.

    PubMed

    Eddy, Justin L; Schroeder, Jay A; Zimbler, Daniel L; Bellows, Lauren E; Lathem, Wyndham W

    2015-12-01

    Many pathogens usurp the host hemostatic system during infection to promote pathogenesis. Yersinia pestis, the causative agent of plague, expresses the plasminogen activator protease Pla, which has been shown in vitro to target and cleave multiple proteins within the fibrinolytic pathway, including the plasmin inhibitor α2-antiplasmin (A2AP). It is not known, however, if Pla inactivates A2AP in vivo; the role of A2AP during respiratory Y. pestis infection is not known either. Here, we show that Y. pestis does not appreciably cleave A2AP in a Pla-dependent manner in the lungs during experimental pneumonic plague. Furthermore, following intranasal infection with Y. pestis, A2AP-deficient mice exhibit no difference in survival time, bacterial burden in the lungs, or dissemination from wild-type mice. Instead, we found that in the absence of Pla, A2AP contributes to the control of the pulmonary inflammatory response during infection by reducing neutrophil recruitment and cytokine production, resulting in altered immunopathology of the lungs compared to A2AP-deficient mice. Thus, our data demonstrate that A2AP is not significantly affected by the Pla protease during pneumonic plague, and although A2AP participates in immune modulation in the lungs, it has limited impact on the course or ultimate outcome of the infection.

  11. Parenteral immunization of PLA/PLGA nanoparticle encapsulating outer membrane protein (Omp) from Aeromonas hydrophila: Evaluation of immunostimulatory action in Labeo rohita (rohu).

    PubMed

    Rauta, Pradipta Ranjan; Nayak, Bismita

    2015-05-01

    Advanced vaccine research approaches needs to explore on biodegradable nanoparticles (NPs) based vaccine carrier that can serve as antigen delivery systems as well as immuno-stimulatory action to induce both innate and adaptive immune response in fish. Immunogenicity of PLA and PLGA NPs encapsulating outer membrane protein (Omp) antigen of Aeromonas hydrophila were evaluated through intra-peritoneal injection in fish, Labeo rohita. Antigen loaded PLA-Omp (223.5 ± 13.19 nm) and PLGA-Omp (166.4 ± 21.23 nm) NPs were prepared using double emulsion method by efficiently encapsulating the antigen reaching the encapsulation efficiency 44 ± 4.58% and 59.33 ± 5.13% respectively. Our formulated PLA Omp and PLGA-Omp NPs were in nanometer range (<500 nm) and could be successfully endocyted in the body. Despite low antigen loading in PLA-Omp, it showed considerably slower antigen release in vitro than PLGA-Omp NPs. Other physical properties like zetapotential values and poly dispersity index (PDI) confirmed the stability as well as monodisperse nature of the formulated nanoparticles. The spherical and isolated nature of PLA-Omp and PLGA-Omp NPs were revealed by SEM analysis. Upon immunization of all antigenic formulations (PLA-Omp NP, PLGA-Omp NP, FIA-Omp, PLA NP, PLGA NP, PBS as control), significant higher bacterial agglutination titre and haemolytic activity were observed in case of PLA-Omp and PLGA-Omp immunized groups than rest groups at both 21 days and 42 days. The specific antibody response was significantly increased and persisted up to 42 days of post immunization by PLA-Omp, PLGA-Omp, FIA-Omp. PLA-Omp NPs showed better immune response (higher bacterial agglutination titre, haemolytic activity, specific antibody titre, higher percent survival upon A. hydrophila challenge) than PLGA-Omp in L. rohita confirming its better efficacy. Comparable antibody response of PLA-Omp and PLGA-Omp with FIA-Omp treated groups suggested that PLA and PLGA could be replacement for

  12. Interaction of characteristic structural elements of persimmon tannin with Chinese cobra PLA2.

    PubMed

    Zhang, Ying; Zhong, Li; Zhou, Bin; Chen, Jin-yu; Li, Chun-mei

    2013-11-01

    To more fully understand the mechanism by which persimmon tannin (PT) inhibited phospholipase A2 (PLA2) and the structural requirements of PT for the inhibition, the interactions between PLA2 and seven characteristic structural elements of PT including epigallocatechin-3-gallate (EGCG), myricetin, epicatechin-3-gallate (ECG), epicatechin-3-gallate-(4β → 8, 2β → O → 7)-epicatechin-3-gallate (A-type ECG dimer), epigallocatechin-3-gallate-(4β → 8, 2β → O → 7)-epigallocatechin-3-gallate (A-type EGCG dimer), epicatechin-(4β → 8, 2β → O → 7)-epicatechin (A-type EC dimer) and epicatechin-(4β → 8)-epicatechin (B-type EC dimer) were studied by enzymatic and spectroscopic methods. Molecular docking was also used to explore the possible residues involved in the interactions. The results revealed that A-type EGCG dimer and A-type ECG dimer showed higher inhibitory effects on the catalytic activity of PLA2 than monomers and B-type dimer. They induced greater conformational changes in PLA2 than other structural elements. In addition, molecular docking studies revealed that expect for lysine residues, other residues such as Trp18, Try27, Gly29, His47 and Tyr63 were involved in the interactions. We propose that A-type EGCG and ECG dimer units may be structural requirements for the interaction between PT and PLA2. Our data provide an additional structural basis for anti-PLA2 activity of persimmon tannin.

  13. Comparison of alkylacylglycerol vs. diacylglycerol as activators of mitogen-activated protein kinase and cytosolic phospholipase A2 in human neutrophil priming.

    PubMed

    Nixon, A B; Seeds, M C; Bass, D A; Smitherman, P K; O'Flaherty, J T; Daniel, L W; Wykle, R L

    1997-08-16

    In human neutrophils, the choline-containing phosphoglycerides contain almost equal amounts of alkylacyl- and diacyl-linked subclasses. In contrast to phosphatidylinositol hydrolysis which yields diacylglycerol, hydrolysis of choline-containing phosphoglycerides by phospholipase D coupled with phosphohydrolase yields both alkylacyl- and diacylglycerol. While diacylglycerol activates protein kinase C, alkylacylglycerol does not, and its role is unclear. Yet previous studies have shown that exogenous alkylacyl- and diacylglycerols can prime for the release of radiolabeled arachidonic acid (AA) in intact neutrophils stimulated by formyl-methionyl-leucyl-phenylalanine. We have now examined the effects of both diacylglycerol (1-oleoyl-2-acetylglycerol; OAG) and alkylacylglycerol (1-O-hexadecyl-2-acetylglycerol; EAG) on the activation of mitogen-activated protein (MAP) kinase and the 85-kDa cytosolic phospholipase A2 (cPLA2) in human neutrophils. We observed that while OAG could effectively activate p42 and p44 MAP kinases along with cPLA2 in a time- and concentration-dependent manner, EAG could not. A novel p40 MAP kinase isoform is also present and activated in response to OAG treatment; the behavior of this MAP kinase isoform is discussed. The activation of cPLA2 and MAP kinase by 20 microM OAG could be inhibited by pretreatment with 1 microM GF-109203X, a selective inhibitor of protein kinase C. Although only OAG activated cPLA2, both OAG and EAG primed for the release of AA mass as determined by gas chromatography/mass spectrometry. The priming of AA release by OAG may be explained by the phosphorylation of cPLA2 through the activation of protein kinase C linked to MAP kinase. However, priming by EAG appears to involve a separate mechanism that is dependent on a different PLA2. Our results support a role for phospholipase D-derived products modulating the activation of cPLA2, further supporting the idea of cross-talk among various phospholipases.

  14. Direct transcriptional control of the plasminogen activator gene of Yersinia pestis by the cyclic AMP receptor protein.

    PubMed

    Kim, Tae-Jong; Chauhan, Sadhana; Motin, Vladimir L; Goh, Ee-Been; Igo, Michele M; Young, Glenn M

    2007-12-01

    Horizontal gene transfer events followed by proper regulatory integration of a gene drive rapid evolution of bacterial pathogens. A key event in the evolution of the highly virulent plague bacterium Yersinia pestis was the acquisition of plasmid pPCP1, which carries the plasminogen activator gene, pla. This promoted the bubonic form of the disease by increasing bacterial dissemination from flea bite sites and incidentally enhanced replication in respiratory airways during pneumonic infection. We determined that expression of pla is controlled by the global regulator cyclic AMP (cAMP) receptor protein (Crp). This transcription factor is well conserved among distantly related bacteria, where it acts as a soluble receptor for the ubiquitous signaling molecule cAMP and controls a global network of metabolic and stress-protective genes. Crp has a similar physiological role in Y. pestis since loss of its function resulted in an inability to metabolize a variety of nonglucose substrates. Activation of pla expression requires a transcription activation element of the pla promoter that serves as a Crp binding site. Crp interaction with this site was demonstrated to occur only in the presence of cAMP. Alteration of the Crp binding site nucleotide sequence prevented in vitro formation of Crp-DNA complexes and inhibited in vivo expression of pla. The placement of pla under direct regulatory control of Crp highlights how highly adapted pathogens integrate laterally acquired genes to coordinate virulence factor expression with global gene networks to maintain homeostasis through the infectious life cycle.

  15. Physical Activity (Exercise)

    MedlinePlus

    ... fitness. Your fitness routine should include aerobic and strength-training activities, and may also include stretching activities. Aerobic ... Examples include walking, jogging, bicycling, swimming, and tennis. Strength-training activities These activities increase the strength and endurance ...

  16. Identification of Lys49-PLA2 from crude venom of Crotalus atrox as a human neutrophil-calcium modulating protein.

    PubMed

    Sultan, Md Tipu; Li, Hong-Mei; Lee, Yong Zu; Lim, Soon Sung; Song, Dong-Keun

    2016-03-01

    We fortuitously observed a human neutrophil intracellular free-calcium concentration ([Ca(2+)]i) increasing activity in the commercially available phosphodiesterase I (PDE I), which is actually dried crude venom of Crotalus atrox. As this activity was not observed with another commercially available pure PDE I, we tried to find out the causative molecule(s) present in 'crude' PDE, and identified Lys49-phospholipase A2 (Lys49-PLA2 or K49-PLA2), a catalytically inactive protein which belongs to the phospholipase A2 family, by activity-driven three HPLC (reverse phase, size exclusion, reverse phase) steps followed by SDS-PAGE and LC-MS/MS. K49-PLA2 induced Ca(2+) infl ux in human neutrophils without any cytotoxic eff ect. Two calcium channel inhibitors, 2-aminoetoxydiphenyl borate (2-APB) (30 µM) and SKF-96365 (20 µM) signifi cantly inhibited K49-PLA2-induced [Ca(2+)]i increase. These results suggest that K49-PLA2 modulates [Ca(2+)]i in human neutrophils via 2-APB- and SKF-96365-sensitive calcium channels without causing membrane disruption.

  17. Identification of Lys49-PLA2 from crude venom of Crotalus atrox as a human neutrophil-calcium modulating protein

    PubMed Central

    Sultan, Md. Tipu; Li, Hong-Mei; Lee, Yong Zu

    2016-01-01

    We fortuitously observed a human neutrophil intracellular free-calcium concentration ([Ca2+]i) increasing activity in the commercially available phosphodiesterase I (PDE I), which is actually dried crude venom of Crotalus atrox. As this activity was not observed with another commercially available pure PDE I, we tried to find out the causative molecule(s) present in 'crude' PDE, and identified Lys49-phospholipase A2 (Lys49-PLA2 or K49-PLA2), a catalytically inactive protein which belongs to the phospholipase A2 family, by activity-driven three HPLC (reverse phase, size exclusion, reverse phase) steps followed by SDS-PAGE and LC-MS/MS. K49-PLA2 induced Ca2+ infl ux in human neutrophils without any cytotoxic eff ect. Two calcium channel inhibitors, 2-aminoetoxydiphenyl borate (2-APB) (30 µM) and SKF-96365 (20 µM) signifi cantly inhibited K49-PLA2-induced [Ca2+]i increase. These results suggest that K49-PLA2 modulates [Ca2+]i in human neutrophils via 2-APB- and SKF-96365-sensitive calcium channels without causing membrane disruption. PMID:26937214

  18. Generation of N-acylphosphatidylethanolamine by members of the phospholipase A/acyltransferase (PLA/AT) family.

    PubMed

    Uyama, Toru; Ikematsu, Natsuki; Inoue, Manami; Shinohara, Naoki; Jin, Xing-Hua; Tsuboi, Kazuhito; Tonai, Takeharu; Tokumura, Akira; Ueda, Natsuo

    2012-09-14

    Bioactive N-acylethanolamines (NAEs), including N-palmitoylethanolamine, N-oleoylethanolamine, and N-arachidonoylethanolamine (anandamide), are formed from membrane glycerophospholipids in animal tissues. The pathway is initiated by N-acylation of phosphatidylethanolamine to form N-acylphosphatidylethanolamine (NAPE). Despite the physiological importance of this reaction, the enzyme responsible, N-acyltransferase, remains molecularly uncharacterized. We recently demonstrated that all five members of the HRAS-like suppressor tumor family are phospholipid-metabolizing enzymes with N-acyltransferase activity and are renamed HRASLS1-5 as phospholipase A/acyltransferase (PLA/AT)-1-5. However, it was poorly understood whether these proteins were involved in the formation of NAPE in living cells. In the present studies, we first show that COS-7 cells transiently expressing recombinant PLA/AT-1, -2, -4, or -5, and HEK293 cells stably expressing PLA/AT-2 generated significant amounts of [(14)C]NAPE and [(14)C]NAE when cells were metabolically labeled with [(14)C]ethanolamine. Second, as analyzed by liquid chromatography-tandem mass spectrometry, the stable expression of PLA/AT-2 in cells remarkably increased endogenous levels of NAPEs and NAEs with various N-acyl species. Third, when NAPE-hydrolyzing phospholipase D was additionally expressed in PLA/AT-2-expressing cells, accumulating NAPE was efficiently converted to NAE. We also found that PLA/AT-2 was partly responsible for NAPE formation in HeLa cells that endogenously express PLA/AT-2. These results suggest that PLA/AT family proteins may produce NAPEs serving as precursors of bioactive NAEs in vivo.

  19. Demonstration of calcium-dependent phospholipase A2 activity in membrane preparation of rabbit neutrophils. Absence of activation by fMet-Leu-Phe, phorbol 12-myristate 13-acetate and A-kinase.

    PubMed Central

    Matsumoto, T; Tao, W; Sha'afi, R I

    1988-01-01

    The presence of a phospholipase A2 (PLA2) activity in rabbit neutrophil membrane preparation that is able to release [1-14C]oleic acid from labelled Escherichia coli has been demonstrated. The activity is critically dependent on the free calcium concentration and marginally stimulated by GTP gamma S. More than 80% of maximal activity is reached at 10 microM-Ca2+. The chemotactic factor, fMet-Leu-Phe, does not stimulate the PLA2 activity in this membrane preparation. Pretreatment of the membrane preparation, under various experimental conditions, or intact cells, before isolation of the membrane with phorbol 12-myristate 13-acetate (PMA), does not affect PLA2 activity. Addition of the catalytic unit of cyclic AMP-dependent kinase to membrane preparation has no effect on PLA2 activity. Pretreatment of the intact neutrophil with dibutyryl-cAMP before isolation of the membrane produces a small but consistent increase in PLA2 activity. The activity of PLA2 in membrane isolated from cells treated with the protein kinase inhibitor 1-(5-isoquinolinesulphonyl)-2-methyl piperazine dihydrochloride (H-7) is significantly decreased. Furthermore, although the addition of PMA to intact rabbit neutrophils has no effect on the release of [3H]arachidonic acid from prelabelled cells, it potentiates significantly the release produced by the calcium ionophore A23187. This potentiation is not due to an inhibition of the acyltransferase activity. H-7 inhibits the basal release of arachidonic acid but does not inhibit the potentiation by PMA. These results suggest several points. (1) fMet-Leu-Phe does not stimulate PLA2 directly, and its ability to release arachidonic acid in intact neutrophils is mediated through its action on phospholipase C. (2) The potentiating effect of PMA on A23187-induced arachidonic acid release is most likely due to PMA affecting either the environment of PLA2 and/or altering the organization of membrane phospholipids in such a way as to increase their

  20. Phospholipase A2 Activity-Dependent Stimulation of Ca2+ Entry by Human Parvovirus B19 Capsid Protein VP1▿

    PubMed Central

    Lupescu, Adrian; Bock, C.-Thomas; Lang, Philipp A.; Aberle, Susanne; Kaiser, Heike; Kandolf, Reinhard; Lang, Florian

    2006-01-01

    Recent reports demonstrated an association of human parvovirus B19 with inflammatory cardiomyopathy (iCMP), which is accompanied by endothelial dysfunction. As intracellular Ca2+ activity is a key regulator of cell function and participates in mechanisms leading to endothelial dysfunction, the present experiments explored the effects of the B19 capsid proteins VP1 and VP2. A secreted phospholipase A2 (PLA2)-like activity has been located in the VP1 unique region of the B19 minor capsid protein. As PLA2 has recently been shown to activate the store-operated or capacitative Ca2+ channel ICRAC, we analyzed the impact of the viral PLA2 motif on Ca2+ entry. We cloned the VP1 and VP2 genes isolated from a patient suffering from fatal B19 iCMP into eukaryotic expression vectors. We also generated a B19 replication-competent plasmid to demonstrate PLA2 activity under the control of the complete B19 genome. After the transfection of human endothelial cells (HMEC-1), cytosolic Ca2+ activity was determined by utilizing Fura-2 fluorescence. VP1 and VP2 expression did not significantly modify basal cytosolic Ca2+ activity or the decline of cytosolic Ca2+ activity following the removal of extracellular Ca2+. However, expression of VP1 and of the full-length B19 clone, but not of VP2, significantly accelerated the increase of cytosolic Ca2+ activity following the readdition of extracellular Ca2+ in the presence of thapsigargin, indicating an activation of ICRAC. The effect of VP1 was mimicked by the PLA2 product lysophosphatidylcholine and abolished by an inactivating mutation of the PLA2-encoding region of the VP1 gene. Our observations point to the activation of Ca2+ entry by VP1 PLA2 activity, an effect likely participating in the pathophysiology of B19 infection. PMID:16956939

  1. Epitope Spreading of Autoantibody Response to PLA2R Associates with Poor Prognosis in Membranous Nephropathy.

    PubMed

    Seitz-Polski, Barbara; Dolla, Guillaume; Payré, Christine; Girard, Christophe A; Polidori, Joel; Zorzi, Kevin; Birgy-Barelli, Eléonore; Jullien, Perrine; Courivaud, Cécile; Krummel, Thierry; Benzaken, Sylvia; Bernard, Ghislaine; Burtey, Stéphane; Mariat, Christophe; Esnault, Vincent L M; Lambeau, Gérard

    2016-05-01

    The phospholipase A2 receptor (PLA2R1) is the major autoantigen in idiopathic membranous nephropathy. However, the value of anti-PLA2R1 antibody titers in predicting patient outcomes is unknown. Here, we screened serum samples from 50 patients positive for PLA2R1 for immunoreactivity against a series of PLA2R1 deletion mutants covering the extracellular domains. We identified reactive epitopes in the cysteine-rich (CysR), C-type lectin domain 1 (CTLD1), and C-type lectin domain 7 (CTLD7) domains and confirmed the reactivity with soluble forms of each domain. We then used ELISAs to stratify 69 patients positive for PLA2R1 by serum reactivity to one or more of these domains: CysR (n=23), CysRC1 (n=14), and CysRC1C7 (n=32). Median ELISA titers measured using the full-length PLA2R1 antigens were not statistically different between subgroups. Patients with anti-CysR-restricted activity were younger (P=0.008), had less nephrotic range proteinuria (P=0.02), and exhibited a higher rate of spontaneous remission (P=0.03) and lower rates of renal failure progression (P=0.002) and ESRD (P=0.01) during follow-up. Overall, 31 of 69 patients had poor renal prognosis (urinary protein/creatinine ratio >4 g/g or eGFR<45 ml/min per 1.73 m(2) at end of follow-up). High anti-PLA2R1 activity and epitope spreading beyond the CysR epitope were independent risk factors of poor renal prognosis in multivariable Cox regression analysis. Epitope spreading during follow-up associated with disease worsening (n=3), whereas reverse spreading from a CysRC1C7 profile back to a CysR profile associated with favorable outcome (n=1). We conclude that analysis of the PLA2R1 epitope profile and spreading is a powerful tool for monitoring disease severity and stratifying patients by renal prognosis.

  2. Constitutive expression of CaPLA1 conferred enhanced growth and grain yield in transgenic rice plants.

    PubMed

    Park, Ki Youl; Kim, Eun Yu; Seo, Young Sam; Kim, Woo Taek

    2016-03-01

    Phospholipids are not only important components of cell membranes, but participate in diverse processes in higher plants. In this study, we generated Capsicum annuum phospholipiase A1 (CaPLA1) overexpressing transgenic rice (Oryza sativa L.) plants under the control of the maize ubiquitin promoter. The T4 CaPLA1-overexpressing rice plants (Ubi:CaPLA1) had a higher root:shoot mass ratio than the wild-type plants in the vegetative stage. Leaf epidermal cells from transgenic plants had more cells than wild-type plants. Genes that code for cyclin and lipid metabolic enzymes were up-regulated in the transgenic lines. When grown under typical paddy field conditions, the transgenic plants produced more tillers, longer panicles and more branches per panicle than the wild-type plants, all of which resulted in greater grain yield. Microarray analysis suggests that gene expressions that are related with cell proliferation, lipid metabolism, and redox state were widely altered in CaPLA1-overexpressing transgenic rice plants. Ubi:CaPLA1 plants had a reduced membrane peroxidation state, as determined by malondialdehyde and conjugated diene levels and higher peroxidase activity than wild-type rice plants. Furthermore, three isoprenoid synthetic genes encoding terpenoid synthase, hydroxysteroid dehydrogenase and 3-hydroxy-3-methyl-glutaryl-CoA reductase were up-regulated in CaPLA1-overexpressing plants. We suggest that constitutive expression of CaPLA1 conferred increased grain yield with enhanced growth in transgenic rice plants by alteration of gene activities related with cell proliferation, lipid metabolism, membrane peroxidation state and isoprenoid biosynthesis.

  3. Constitutive expression of CaPLA1 conferred enhanced growth and grain yield in transgenic rice plants.

    PubMed

    Park, Ki Youl; Kim, Eun Yu; Seo, Young Sam; Kim, Woo Taek

    2016-03-01

    Phospholipids are not only important components of cell membranes, but participate in diverse processes in higher plants. In this study, we generated Capsicum annuum phospholipiase A1 (CaPLA1) overexpressing transgenic rice (Oryza sativa L.) plants under the control of the maize ubiquitin promoter. The T4 CaPLA1-overexpressing rice plants (Ubi:CaPLA1) had a higher root:shoot mass ratio than the wild-type plants in the vegetative stage. Leaf epidermal cells from transgenic plants had more cells than wild-type plants. Genes that code for cyclin and lipid metabolic enzymes were up-regulated in the transgenic lines. When grown under typical paddy field conditions, the transgenic plants produced more tillers, longer panicles and more branches per panicle than the wild-type plants, all of which resulted in greater grain yield. Microarray analysis suggests that gene expressions that are related with cell proliferation, lipid metabolism, and redox state were widely altered in CaPLA1-overexpressing transgenic rice plants. Ubi:CaPLA1 plants had a reduced membrane peroxidation state, as determined by malondialdehyde and conjugated diene levels and higher peroxidase activity than wild-type rice plants. Furthermore, three isoprenoid synthetic genes encoding terpenoid synthase, hydroxysteroid dehydrogenase and 3-hydroxy-3-methyl-glutaryl-CoA reductase were up-regulated in CaPLA1-overexpressing plants. We suggest that constitutive expression of CaPLA1 conferred increased grain yield with enhanced growth in transgenic rice plants by alteration of gene activities related with cell proliferation, lipid metabolism, membrane peroxidation state and isoprenoid biosynthesis. PMID:26803502

  4. [Adapting physical activities for an active retirement].

    PubMed

    Renaudie, François

    2016-01-01

    The benefits of doing adapted physical exercise for elderly people have been proven. For more than thirty years, the French Federation for an Active Retirement has been striving to help people age well by proposing multiple activities to remain in good health after the age of 50. Doctors, activity leaders and federal instructors are attentive to each individual's capacities. PMID:27449307

  5. Leptin rapidly activates PPARs in C2C12 muscle cells

    SciTech Connect

    Bendinelli, Paola; Piccoletti, Roberta . E-mail: Roberta.Piccoletti@unimi.it; Maroni, Paola

    2005-07-08

    Experimental evidence suggests that leptin operates on the tissues, including skeletal muscle, also by modulating gene expression. Using electrophoretic mobility shift assays, we have shown that physiological doses of leptin promptly increase the binding of C2C12 cell nuclear extracts to peroxisome proliferator-activated receptor (PPAR) response elements in oligonucleotide probes and that all three PPAR isoforms participate in DNA-binding complexes. We pre-treated C2C12 cells with AACOCF{sub 3}, a specific inhibitor of cytosolic phospholipase A{sub 2} (cPLA{sub 2}), an enzyme that supplies ligands to PPARs, and found that it abrogates leptin-induced PPAR DNA-binding activity. Leptin treatment significantly increased cPLA{sub 2} activity, evaluated as the release of [{sup 3}H]arachidonic acid from pre-labelled C2C12 cells, as well as phosphorylation. Further, using MEK1 inhibitor PD-98059 we showed that leptin activates cPLA{sub 2} through ERK induction. These results support a direct effect of leptin on skeletal muscle cells, and suggest that the hormone may modulate muscle transcription also by precocious activation of PPARs through ERK-cPLA{sub 2} pathway.

  6. Learning as Activity.

    ERIC Educational Resources Information Center

    Jonassen, David H.

    2002-01-01

    Integrates contemporary theories of learning into a theory of learning as activity. Explains ecological psychology, changes in understanding of learning, activity systems and activity theory (including the integration of consciousness and activity), and activity structure; and discusses learning as a cognitive and social process. (LRW)

  7. Cytosolic and Calcium-Independent Phospholipases A2 Activation and Prostaglandins E2 Are Associated with Escherichia coli-Induced Reduction of Insulin Secretion in INS-1E Cells

    PubMed Central

    Scalia, Marina; Motta, Carla; Parrino, Cristina; Frittitta, Lucia; Olivieri, Melania; Cristaldi, Martina; Avola, Roberto; Bramanti, Vincenzo; Toscano, Maria Antonietta; Anfuso, Carmelina Daniela; Lupo, Gabriella

    2016-01-01

    It is suspected that microbial infections take part in the pathogenesis of diabetes mellitus type 1 (T1DM). Glucose-induced insulin secretion is accompanied by the release of free arachidonic acid (AA) mainly by cytosolic- and calcium independent phospholipases A2 (cPLA2 and iPLA2). Insulinoma cell line (INS-1E) was infected with E. coli isolated from the blood culture of a patient with sepsis. Invasion assay, Scanning Electron Microscopy and Transmission Electron Microscopy demonstrated the capacity of E. coli to enter cells, which was reduced by PLA2 inhibitors. Glucose-induced insulin secretion was significantly increased after acute infection (8h) but significantly decreased after chronic infection (72h). PLA2 activities, cPLA2, iPLA2, phospho-cPLA2, and COX-2 expressions were increased after acute and, even more, after chronic E. coli infection. The silencing of the two isoforms of PLA2s, with specific cPLA2- or iPLA2-siRNAs, reduced insulin secretion after acute infection and determined a rise in insulin release after chronic infection. Prostaglandins E2 (PGE2) production was significantly elevated in INS-1E after long-term E. coli infection and the restored insulin secretion in presence of L798106, a specific EP3 antagonist, and NS-398, a COX-2 inhibitor, and the reduction of insulin secretion in presence of sulprostone, a specific EP3 agonist, revealed their involvement in the effects triggered by bacterial infection. The results obtained demonstrated that cPLA2 and iPLA2 play a key role in insulin secretion process after E. coli infection. The high concentration of AA released is transformed into PGE2, which could be responsible for the reduced insulin secretion. PMID:27631977

  8. Cytosolic and Calcium-Independent Phospholipases A2 Activation and Prostaglandins E2 Are Associated with Escherichia coli-Induced Reduction of Insulin Secretion in INS-1E Cells.

    PubMed

    Caporarello, Nunzia; Salmeri, Mario; Scalia, Marina; Motta, Carla; Parrino, Cristina; Frittitta, Lucia; Olivieri, Melania; Cristaldi, Martina; Avola, Roberto; Bramanti, Vincenzo; Toscano, Maria Antonietta; Anfuso, Carmelina Daniela; Lupo, Gabriella

    2016-01-01

    It is suspected that microbial infections take part in the pathogenesis of diabetes mellitus type 1 (T1DM). Glucose-induced insulin secretion is accompanied by the release of free arachidonic acid (AA) mainly by cytosolic- and calcium independent phospholipases A2 (cPLA2 and iPLA2). Insulinoma cell line (INS-1E) was infected with E. coli isolated from the blood culture of a patient with sepsis. Invasion assay, Scanning Electron Microscopy and Transmission Electron Microscopy demonstrated the capacity of E. coli to enter cells, which was reduced by PLA2 inhibitors. Glucose-induced insulin secretion was significantly increased after acute infection (8h) but significantly decreased after chronic infection (72h). PLA2 activities, cPLA2, iPLA2, phospho-cPLA2, and COX-2 expressions were increased after acute and, even more, after chronic E. coli infection. The silencing of the two isoforms of PLA2s, with specific cPLA2- or iPLA2-siRNAs, reduced insulin secretion after acute infection and determined a rise in insulin release after chronic infection. Prostaglandins E2 (PGE2) production was significantly elevated in INS-1E after long-term E. coli infection and the restored insulin secretion in presence of L798106, a specific EP3 antagonist, and NS-398, a COX-2 inhibitor, and the reduction of insulin secretion in presence of sulprostone, a specific EP3 agonist, revealed their involvement in the effects triggered by bacterial infection. The results obtained demonstrated that cPLA2 and iPLA2 play a key role in insulin secretion process after E. coli infection. The high concentration of AA released is transformed into PGE2, which could be responsible for the reduced insulin secretion. PMID:27631977

  9. An Evaluation of 3-Rhamnosylquercetin, a Glycosylated Form of Quercetin, against the Myotoxic and Edematogenic Effects of sPLA2 from Crotalus durissus terrificus

    PubMed Central

    Toyama, Daniela de Oliveira; Gaeta, Henrique Hessel; de Pinho, Marcus Vinícius Terashima; Ferreira, Marcelo José Pena; Romoff, Paulete; Matioli, Fábio Filippi; Magro, Angelo José; Fontes, Marcos Roberto de Mattos; Toyama, Marcos Hikari

    2014-01-01

    This paper shows the results of quercitrin effects on the structure and biological activity of secretory phospholipase (sPLA2) from Crotalus durissus terrificus, which is the main toxin involved in the pharmacological effects of this snake venom. According to our mass spectrometry and circular dichroism results, quercetin was able to promote a chemical modification of some amino acid residues and modify the secondary structure of C. d. terrificus sPLA2. Moreover, molecular docking studies showed that quercitrin can establish chemical interactions with some of the crucial amino acid residues involved in the enzymatic activity of the sPLA2, indicating that this flavonoid could also physically impair substrate molecule access to the catalytic site of the toxin. Additionally, in vitro and in vivo assays showed that the quercitrin strongly diminished the catalytic activity of the protein, altered its Vmax and Km values, and presented a more potent inhibition of essential pharmacological activities in the C. d. terrificus sPLA2, such as its myotoxicity and edematogenic effect, in comparison to quercetin. Thus, we concluded that the rhamnose group found in quercitrin is most likely essential to the antivenom activities of this flavonoid against C. d. terrificus sPLA2. PMID:24696848

  10. [Anti-phospholipase A2 receptor (anti-PLA2R) antibodies and idiopathic membranous nephropathy: which role in diagnosis and prognosis of this disease?].

    PubMed

    Netti, Giuseppe Stefano; Ranieri, Elena

    2014-01-01

    The discovery of the M-type phospholipase A2 receptor (PLA2R) as a major antigen in idiopathic membranous nephropathy (iMN) was a breakthrough in understanding the pathogenesis of this disease, establishing iMN as an autoimmune disease. Subsequent studies confirmed that detection of circulating antibodies against PLA2R was positive in approximately 70% of incident iMN patients. We discuss several studies that have suggested the potential role of measuring PLA2R antibodies for clinical practice. Recently, it has been shown that the presence of PLA2R antibodies supported a diagnosis of iMN, changes in antibody levels were related to clinical disease activity, disappearance of antibodies preceded and predicted subsequent decrease of proteinuria and high titers of antibodies were associated with a low likelihood spontaneous remission.

  11. Physical Activity Assessment

    Cancer.gov

    Current evidence convincingly indicates that physical activity reduces the risk of colon and breast cancer. Physical activity may also reduce risk of prostate cancer. Scientists are also evaluating potential relationships between physical activity and other cancers.

  12. Facts about Physical Activity

    MedlinePlus

    ... Physical Activity Overweight & Obesity Healthy Weight Breastfeeding Micronutrient Malnutrition State and Local Programs Facts about Physical Activity ... Physical Activity Overweight & Obesity Healthy Weight Breastfeeding Micronutrient Malnutrition State and Local Programs File Formats Help: How ...

  13. Activation of group IVC phospholipase A(2) by polycyclic aromatic hydrocarbons induces apoptosis of human coronary artery endothelial cells.

    PubMed

    Tithof, Patricia K; Richards, Sean M; Elgayyar, Mona A; Menn, Fu-Minn; Vulava, Vijay M; McKay, Larry; Sanseverino, John; Sayler, Gary; Tucker, Dawn E; Leslie, Christina C; Lu, Kim P; Ramos, Kenneth S

    2011-06-01

    Exposure to environmental pollutants, such as polycyclic aromatic hydrocarbons (PAHs) found in coal tar mixtures and tobacco sources, is considered a significant risk factor for the development of heart disease in humans. The goal of this study was to determine the influence of PAHs present at a Superfund site on human coronary artery endothelial cell (HCAEC) phospholipase A(2) (PLA(2)) activity and apoptosis. Extremely high levels of 12 out of 15 EPA high-priority PAHs were present in both the streambed and floodplain sediments at a site where an urban creek and its adjacent floodplain were extensively contaminated by PAHs and other coal tar compounds. Nine of the 12 compounds and a coal tar mixture (SRM 1597A) activated group IVC PLA(2) in HCAECs, and activation of this enzyme was associated with histone fragmentation and poly (ADP) ribose polymerase (PARP) cleavage. Genetic silencing of group IVC PLA(2) inhibited both (3)H-fatty acid release and histone fragmentation by PAHs and SRM 1597A, indicating that individual PAHs and a coal tar mixture induce apoptosis of HCAECs via a mechanism that involves group IVC PLA(2). Western blot analysis of aortas isolated from feral mice (Peromyscus leucopus) inhabiting the Superfund site showed increased PARP and caspase-3 cleavage when compared to reference mice. These data suggest that PAHs induce apoptosis of HCAECs via activation of group IVC PLA(2). PMID:21132278

  14. Molecular Characterization of Lys49 and Asp49 Phospholipases A2 from Snake Venom and Their Antiviral Activities against Dengue virus

    PubMed Central

    Cecilio, Alzira B.; Caldas, Sergio; De Oliveira, Raiana A.; Santos, Arthur S. B.; Richardson, Michael; Naumann, Gustavo B.; Schneider, Francisco S.; Alvarenga, Valeria G.; Estevão-Costa, Maria I.; Fuly, Andre L.; Eble, Johannes A.; Sanchez, Eladio F.

    2013-01-01

    We report the detailed molecular characterization of two PLA2s, Lys49 and Asp49 isolated from Bothrops leucurus venom, and examined their effects against Dengue virus (DENV). The Bl-PLA2s, named BlK-PLA2 and BlD-PLA2, are composed of 121 and 122 amino acids determined by automated sequencing of the native proteins and peptides produced by digestion with trypsin. They contain fourteen cysteines with pIs of 9.05 and 8.18 for BlK- and BlD-PLA2s, and show a high degree of sequence similarity to homologous snake venom PLA2s, but may display different biological effects. Molecular masses of 13,689.220 (Lys49) and 13,978.386 (Asp49) were determined by mass spectrometry. DENV causes a prevalent arboviral disease in humans, and no clinically approved antiviral therapy is currently available to treat DENV infections. The maximum non-toxic concentration of the proteins to LLC-MK2 cells determined by MTT assay was 40 µg/mL for Bl-PLA2s (pool) and 20 µg/mL for each isoform. Antiviral effects of Bl-PLA2s were assessed by quantitative Real-Time PCR. Bl-PLA2s were able to reduce DENV-1, DENV-2, and DENV-3 serotypes in LLC-MK2 cells infection. Our data provide further insight into the structural properties and their antiviral activity against DENV, opening up possibilities for biotechnological applications of these Bl-PLA2s as tools of research. PMID:24131891

  15. Enzyme activities in activated sludge flocs.

    PubMed

    Yu, Guang-Hui; He, Pin-Jing; Shao, Li-Ming; Lee, Duu-Jong

    2007-12-01

    This study quantified the activities of enzymes in extracellular polymeric substances (EPS) and in pellets. Seven commonly adopted extraction schemes were utilized to extract from aerobic flocs the contained EPS, which were further categorized into loosely bound (LB) and tightly bound (TB) fractions. Ultrasonication effectively extracted the EPS from sludge flocs. Enzyme assay tests showed that the protease activity was localized mainly on the pellets, alpha-amylase and alpha-glucosidase activities were largely bound with LB-EPS, and few protease, alpha-amylase, or alpha-glucosidase activities were associated with the TB-EPS fraction. There exists no correlation between the biochemical compositions of EPS and the distribution of enzyme activities in the sludge matrix. The 44-65% of alpha-amylase and 59-100% of alpha-glucosidase activities noted with the LB-EPS indicate heterogeneous hydrolysis patterns in the sludge flocs with proteins and carbohydrates.

  16. Carbohydrate Mouth Rinse Maintains Muscle Electromyographic Activity and Increases Time to Exhaustion during Moderate but not High-Intensity Cycling Exercise

    PubMed Central

    Bastos-Silva, Victor José; Melo, Alan de Albuquerque; Lima-Silva, Adriano Eduardo; Moura, Felipe Arruda; Bertuzzi, Rômulo; de Araujo, Gustavo Gomes

    2016-01-01

    The aim was to investigate the influence of a carbohydrate (CHO) mouth rinse on the vastus lateralis (VL) and rectus femoris (RF) electromyographic activity (EMG) and time to exhaustion (TE) during moderate (MIE) and high-intensity cycling exercise (HIE). Thirteen participants cycled at 80% of their respiratory compensation point and at 110% of their peak power output to the point of exhaustion. Before the trials and every 15 min during MIE, participants rinsed with the CHO or Placebo (PLA) solutions. The root mean square was calculated. CHO had no effect on the TE during HIE (CHO: 177.3 ± 42.2 s; PLA: 163.0 ± 26.7 s, p = 0.10), but the TE was increased during MIE (CHO: 76.6 ± 19.7 min; PLA: 65.4 ± 15.2 min; p = 0.01). The EMG activity in the VL was higher than PLA at 30 min (CHO: 10.5% ± 2.6%; PLA: 7.7% ± 3.3%; p = 0.01) and before exhaustion (CHO: 10.3% ± 2.5%; PLA: 8.0% ± 2.9%; p = 0.01) with CHO rinsing. There was no CHO effect on the EMG activity of RF during MIE or for VL and RF during HIE. CHO mouth rinse maintains EMG activity and enhances performance for MIE but not for HIE. PMID:27005660

  17. Carbohydrate Mouth Rinse Maintains Muscle Electromyographic Activity and Increases Time to Exhaustion during Moderate but not High-Intensity Cycling Exercise.

    PubMed

    Bastos-Silva, Victor José; Melo, Alan de Albuquerque; Lima-Silva, Adriano Eduardo; Moura, Felipe Arruda; Bertuzzi, Rômulo; de Araujo, Gustavo Gomes

    2016-03-01

    The aim was to investigate the influence of a carbohydrate (CHO) mouth rinse on the vastus lateralis (VL) and rectus femoris (RF) electromyographic activity (EMG) and time to exhaustion (TE) during moderate (MIE) and high-intensity cycling exercise (HIE). Thirteen participants cycled at 80% of their respiratory compensation point and at 110% of their peak power output to the point of exhaustion. Before the trials and every 15 min during MIE, participants rinsed with the CHO or Placebo (PLA) solutions. The root mean square was calculated. CHO had no effect on the TE during HIE (CHO: 177.3 ± 42.2 s; PLA: 163.0 ± 26.7 s, p = 0.10), but the TE was increased during MIE (CHO: 76.6 ± 19.7 min; PLA: 65.4 ± 15.2 min; p = 0.01). The EMG activity in the VL was higher than PLA at 30 min (CHO: 10.5% ± 2.6%; PLA: 7.7% ± 3.3%; p = 0.01) and before exhaustion (CHO: 10.3% ± 2.5%; PLA: 8.0% ± 2.9%; p = 0.01) with CHO rinsing. There was no CHO effect on the EMG activity of RF during MIE or for VL and RF during HIE. CHO mouth rinse maintains EMG activity and enhances performance for MIE but not for HIE. PMID:27005660

  18. Inhibition of Neurotoxic Secretory Phospholipases A2 Enzymatic, Edematogenic, and Myotoxic Activities by Harpalycin 2, an Isoflavone Isolated from Harpalyce brasiliana Benth

    PubMed Central

    Ximenes, Rafael M.; Rabello, Marcelo M.; Araújo, Renata M.; Silveira, Edilberto R.; Fagundes, Fábio H. R.; Diz-Filho, Eduardo B. S.; Buzzo, Simone C.; Soares, Veronica C. G.; Toyama, Daniela de O.; Gaeta, Henrique H.; Hernandes, Marcelo Z.; Monteiro, Helena S. A.; Toyama, Marcos H.

    2012-01-01

    Secretory phospholipases A2 (sPLA2) exert proinflammatory actions through lipid mediators. These enzymes have been found to be elevated in many inflammatory disorders such as rheumatoid arthritis, sepsis, and atherosclerosis. The aim of this study was to evaluate the effect of harpalycin 2 (Har2), an isoflavone isolated from Harpalyce brasiliana Benth., in the enzymatic, edematogenic, and myotoxic activities of sPLA2 from Bothrops pirajai, Crotalus durissus terrificus, Apis mellifera, and Naja naja venoms. Har2 inhibits all sPLA2 tested. PrTX-III (B. pirajai venom) was inhibited at about 58.7%, Cdt F15 (C. d. terrificus venom) at 78.8%, Apis (from bee venom) at 87.7%, and Naja (N. naja venom) at 88.1%. Edema induced by exogenous sPLA2 administration performed in mice paws showed significant inhibition by Har2 at the initial step. In addition, Har2 also inhibited the myotoxic activity of these sPLA2s. In order to understand how Har2 interacts with these enzymes, docking calculations were made, indicating that the residues His48 and Asp49 in the active site of these enzymes interacted powerfully with Har2 through hydrogen bonds. These data pointed to a possible anti-inflammatory activity of Har2 through sPLA2 inhibition. PMID:22899963

  19. Antimicrobial activity of nisin incorporated in pectin and polylactic acid composite films against Listeria monocytogenes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Extruded composite films from 20% pectin and 80% polylactic acids (PLA) were developed and nisin was loaded into films by a diffusion post extrusion. Inhibitory activities of the films against Listeria monocytogenes were evaluated in brain heart infusion (BHI) broth, liquid egg white and orange juic...

  20. Localization of nonpancreatic secretory phospholipase A2 in normal and atherosclerotic arteries. Activity of the isolated enzyme on low-density lipoproteins.

    PubMed

    Hurt-Camejo, E; Andersen, S; Standal, R; Rosengren, B; Sartipy, P; Stadberg, E; Johansen, B

    1997-02-01

    Secretory nonpancreatic type II phospholipase A2 (snpPLA2) hydrolyzes fatty acids at the sn-2 position in phospholipids releasing free fatty acids (FFAs) and lysophospholipids. These products may act as intracellular second messengers or can be further metabolized into proinflammatory lipid mediators. The presence of snpPLA2 in extracellular fluids and serum during inflammation has suggested a role of the enzyme in this process. However, the presence of snpPLA2 in a variety of normal tissues suggests that snpPLA2 may also have physiological functions. Atherosclerosis appears to have an inflammatory component. Here we report on the snpPLA2 localization in normal and atherosclerotic lesions and on the properties of the isolated enzyme. A strong snpPLA2 immunoreactivity was observed in the arterial media that was colocalized with alpha-actin-positive vascular smooth muscle cells (SMCs) in both normal and atherosclerotic vessels. In aortic atherosclerotic lesions, snpPLA2 was observed colocalized with CD68-positive macrophages and HHF-35-positive SMCs and extracellularly in the lipid core. snpPLA2 was isolated from human normal arteries and from aorta with lesions. The enzyme was isolated by acid extraction of normal arterial tissues followed by immunoaffinity chromatography. The purified snpPLA2 had an expected molecular weight of 14 kD by polyacrylamide gel electrophoresis and appeared as a single band in immunoblotting. The enzymatic activity was followed by measuring release of fatty acids from phospholipid liposomes or LDL as substrates. The enzymatic activity was inhibited with two specific inhibitors for human snpPLA2: (1) monoclonal antibody 187 and (2) LY311727, a synthetic selective inhibitor. The mRNA for snpPLA2 was detected with reverse transcriptase polymerase chain reaction. These results indicate that snpPLA2 is present in human arteries and that it is able to hydrolyze phospholipids in LDL. The results support the hypothesis that snpPLA2 can release

  1. Chitosan/PLA nanoparticles as a novel carrier for the delivery of anthraquinone: synthesis, characterization and in vitro cytotoxicity evaluation.

    PubMed

    Jeevitha, D; Amarnath, Kanchana

    2013-01-01

    Designing novel materials for biomedical applications generally require the use of biodegradable materials. This study aims to engineer a biodegradable [chitosan (CS) and poly (lactic acid) (PLA)] as AQ carrier with nanometer dimensions and to evaluate the anticancer potency of the prepared CS/PLA-AQ NPs in human carcinoma (HepG2) cells. CS-PLA complex, which are well dispersed and stable in aqueous solution, was prepared by the precipitation of lactic acid in chitosan solution by dropping method and characterized by SEM, TEM, DLS and FTIR. The results thus displayed that the prepared nanoparticles carried a positive charge and showed the size in the range from 100 to 200 nm. The in vitro (AQ) release study showed that these nanoparticles provided a continuous release of the entrapped AQ for 10 days, and the release behavior was influenced by the pH value of the medium thereby making feasible to develop CS-PLA for enhanced and sustained release of AQ. MTT assay revealed higher cytotoxic efficacy of CS/PLA-AQ NPs than Free AQ in HepG2 cells. Further, the mitochondrial membrane damage indicated by loss of mitochondrial membrane potential and necrotic cell death could be attributed to the increased reactive oxygen species production. Our results also suggest that upon CS/PLA-AQ NPs exposure the cell viability decreased due to apoptosis, as demonstrated by the formation of apoptotic bodies, sub-G1 hypodiploid cells, and DNA fragmentation. Henceforth, CS/PLA-AQ NPs demonstrated a strong antitumor activity in vitro by reducing cell viability, inducing cell necrosis, decreasing the negative surface charge and mitochondrial membrane potential, and fragmenting DNA.

  2. Anti-listeria activity of poly(lactic acid)/sawdust particle biocomposite film impregnated with pediocin PA-1/AcH and its use in raw sliced pork.

    PubMed

    Woraprayote, Weerapong; Kingcha, Yutthana; Amonphanpokin, Pannawit; Kruenate, Jittiporn; Zendo, Takeshi; Sonomoto, Kenji; Benjakul, Soottawat; Visessanguan, Wonnop

    2013-10-15

    A novel poly(lactic acid) (PLA)/sawdust particle (SP) biocomposite film with anti-listeria activity was developed by incorporation of pediocin PA-1/AcH (Ped) using diffusion coating method. Sawdust particle played an important role in embedding pediocin into the hydrophobic PLA film. The anti-listeria activity of the PLA/SP biocomposite film incorporated with Ped (PLA/SP+Ped) was detected, while no activity against the tested pathogen was observed for the control PLA films (without SP and/or Ped). Dry-heat treatment of film before coating with Ped resulted in the highest Ped adsorption (11.63 ± 3.07 μg protein/cm(2)) and the highest anti-listeria activity. A model study of PLA/SP+Ped as a food-contact antimicrobial packaging on raw sliced pork suggests a potential inhibition of Listeria monocytogenes (99% of total listerial population) on raw sliced pork during the chilled storage. This study supports the feasibility of using PLA/SP+Ped film to reduce the initial load of L. monocytogenes on the surface of raw pork.

  3. Active commuting to school

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Declines in physical activity levels have coincided with increasing rates of obesity in children. This is problematic because physical activity has been shown to attenuate weight gain in children. Active commuting to school is one way of increasing children's physical activity. However, given the hi...

  4. Home Activities for Fours.

    ERIC Educational Resources Information Center

    Ferguson-Florissant School District, Ferguson, MO.

    These home learning activity guides have been developed for parents to use with their 4-year-old children. Most of the activities require only household items that are often thrown away and can be recycled for learning activities. Some require no materials at all. The guides frequently begin with a discussion of home activities; progress through…

  5. [Positive Activities Campaign.

    ERIC Educational Resources Information Center

    Substance Abuse and Mental Health Services Administration (DHHS/PHS), Rockville, MD. Center for Substance Abuse Prevention.

    This packet contains four pamphlets that are part of a campaign to encourage adults to provide and promote positive activities for youth and to serve as role models for young people. "Positive Activities: A Campaign for Youth" includes information on what positive activities are, how to get involved in helping to provide positive activities for…

  6. Increasing Youth Physical Activity with Activity Calendars

    ERIC Educational Resources Information Center

    Eckler, Seth

    2016-01-01

    Physical educators often struggle with ways to get their students to be active beyond the school day. One strategy to accomplish this is the use of physical activity calendars (PACs). The purpose of this article is to support the use of PACs and give practical advice for creating effective PACs.

  7. PHEA-PLA biocompatible nanoparticles by technique of solvent evaporation from multiple emulsions.

    PubMed

    Cavallaro, Gennara; Craparo, Emanuela Fabiola; Sardo, Carla; Lamberti, Gaetano; Barba, Anna Angela; Dalmoro, Annalisa

    2015-11-30

    Nanocarriers of amphiphilic polymeric materials represent versatile delivery systems for poorly water soluble drugs. In this work the technique of solvent evaporation from multiple emulsions was applied to produce nanovectors based on new amphiphilic copolymer, the α,β-poly(N-2-hydroxyethyl)-DL-aspartamide-polylactic acid (PHEA-PLA), purposely synthesized to be used in the controlled release of active molecules poorly soluble in water. To this aim an amphiphilic derivative of PHEA, a hydrophilic polymer, was synthesized by derivatization of the polymeric backbone with hydrophobic grafts of polylactic acid (PLA). The achieved copolymer was thus used to produce nanoparticles loaded with α tocopherol (vitamin E) adopted as lipophilic model molecule. Applying a protocol based on solvent evaporation from multiple emulsions assisted by ultrasonic energy and optimizing the emulsification process (solvent selection/separation stages), PHEA-PLA nanostructured particles with total α tocopherol entrapment efficiency (100%), were obtained. The drug release is expected to take place in lower times with respect to PLA due to the presence of the hydrophilic PHEA, therefore the produced nanoparticles can be used for semi-long term release drug delivery systems.

  8. Correlation between crystallization behaviour and interfacial interactions in plasticized PLA/POSS nanocomposites

    NASA Astrophysics Data System (ADS)

    Kodal, Mehmet; Şirin, Hümeyra; Özkoç, Güralp

    2016-03-01

    In this study, the correlation between crystallization behavior and surface chemistry of polyhedral oligomeric silsesquioxanes (POSS) for plasticized poly(lactic acid) (PLA)/POSS nanocomposites was investigated. Four different kinds of POSS particles having different chemical structures were used. Poly(ethylene glycol) (PEG, 8000 g/mol) was utilized as the plasticiser. The nanocomposites were melt-compounded in an Xplore Instruments 15 cc twin screw microcompounder at 180°C barrel temperature and 100 rpm screw speed. Non-isothermal crystallization behaviour of PLA/PEG/POSS nanocomposites were evaluated from common kinetic models such as Avrami and Avrami-Ozawa and Kissinger by using the thermal data obtained from differantial scanning calorimetry (DSC). A polarized optical microscope (POM) equipped with a hot-stage was used to examine the morphology during the crystal growth. In order to investigate the interfacial interactions between POSS particles and plasticized PLA, thermodynamic work of adhesion approach was adopted using the experimentally determined surface energies. A strong correlation was obtained between interfacial chemistry and the nucleation rate in plasticized PLA/POSS nanocomposites. It was found that the polar interactions were the dominating factor which determines the nucleation activity of the POSS particles.

  9. The M-type receptor PLA2R regulates senescence through the p53 pathway.

    PubMed

    Augert, Arnaud; Payré, Christine; de Launoit, Yvan; Gil, Jesus; Lambeau, Gérard; Bernard, David

    2009-03-01

    Senescence is a stable proliferative arrest induced by various stresses such as telomere erosion, oncogenic or oxidative stress. Compelling evidence suggests that it acts as a barrier against tumour development. Describing new mechanisms that favour an escape from senescence can thus reveal new insights into tumorigenesis. To identify new genes controlling the senescence programme, we performed a loss-of-function genetic screen in primary human fibroblasts. We report that knockdown of the M-type receptor PLA2R (phospholipase A2 receptor) prevents the onset of replicative senescence and diminishes stress-induced senescence. Interestingly, expression of PLA2R increases during replicative senescence, and its ectopic expression results in premature senescence. We show that PLA2R regulates senescence in a reactive oxygen species-DNA damage-p53-dependent manner. Taken together, our study identifies PLA2R as a potential new tumour suppressor gene crucial in the induction of cellular senescence through the activation of the p53 pathway.

  10. The M-type receptor PLA2R regulates senescence through the p53 pathway

    PubMed Central

    Augert, Arnaud; Payré, Christine; de Launoit, Yvan; Gil, Jesus; Lambeau, Gérard; Bernard, David

    2009-01-01

    Senescence is a stable proliferative arrest induced by various stresses such as telomere erosion, oncogenic or oxidative stress. Compelling evidence suggests that it acts as a barrier against tumour development. Describing new mechanisms that favour an escape from senescence can thus reveal new insights into tumorigenesis. To identify new genes controlling the senescence programme, we performed a loss-of-function genetic screen in primary human fibroblasts. We report that knockdown of the M-type receptor PLA2R (phospholipase A2 receptor) prevents the onset of replicative senescence and diminishes stress-induced senescence. Interestingly, expression of PLA2R increases during replicative senescence, and its ectopic expression results in premature senescence. We show that PLA2R regulates senescence in a reactive oxygen species–DNA damage–p53-dependent manner. Taken together, our study identifies PLA2R as a potential new tumour suppressor gene crucial in the induction of cellular senescence through the activation of the p53 pathway. PMID:19197340

  11. PHEA-PLA biocompatible nanoparticles by technique of solvent evaporation from multiple emulsions.

    PubMed

    Cavallaro, Gennara; Craparo, Emanuela Fabiola; Sardo, Carla; Lamberti, Gaetano; Barba, Anna Angela; Dalmoro, Annalisa

    2015-11-30

    Nanocarriers of amphiphilic polymeric materials represent versatile delivery systems for poorly water soluble drugs. In this work the technique of solvent evaporation from multiple emulsions was applied to produce nanovectors based on new amphiphilic copolymer, the α,β-poly(N-2-hydroxyethyl)-DL-aspartamide-polylactic acid (PHEA-PLA), purposely synthesized to be used in the controlled release of active molecules poorly soluble in water. To this aim an amphiphilic derivative of PHEA, a hydrophilic polymer, was synthesized by derivatization of the polymeric backbone with hydrophobic grafts of polylactic acid (PLA). The achieved copolymer was thus used to produce nanoparticles loaded with α tocopherol (vitamin E) adopted as lipophilic model molecule. Applying a protocol based on solvent evaporation from multiple emulsions assisted by ultrasonic energy and optimizing the emulsification process (solvent selection/separation stages), PHEA-PLA nanostructured particles with total α tocopherol entrapment efficiency (100%), were obtained. The drug release is expected to take place in lower times with respect to PLA due to the presence of the hydrophilic PHEA, therefore the produced nanoparticles can be used for semi-long term release drug delivery systems. PMID:26410757

  12. Inhibition of the phospholipase A2 activity of peroxiredoxin 6 prevents lung damage with exposure to hyperoxia

    PubMed Central

    Benipal, Bavneet; Feinstein, Sheldon I.; Chatterjee, Shampa; Dodia, Chandra; Fisher, Aron B.

    2015-01-01

    Lung injury associated with hyperoxia reflects in part the secondary effects of pulmonary inflammation and the associated production of reactive oxygen species due to activation of NADPH oxidase, type 2 (NOX2). Activation of NOX2 requires the phospholipase A2 (PLA2) activity of peroxiredoxin 6 (Prdx6). Therefore, we evaluated whether blocking Prdx6 PLA2 activity using the inhibitor MJ33 would be protective in a mouse model of acute lung injury resulting from hyperoxic exposure. Mice were treated with an intraperitoneal injection of MJ33 (2.5 nmol/g body weight) at the start of exposure (zero time) and at 48 h during continuous exposure to 100% O2 for 80 h. Treatment with MJ33 reduced the number of neutrophils and the protein content in the fluid obtained by bronchoalveolar lavage, inhibited the increase in lipid peroxidation products in lung tissue, decreased the number of apoptotic cells in the lung, and decreased the perivascular edema associated with the 80 h exposure to hyperoxia. Thus, blocking Prdx6 PLA2 activity by MJ33 significantly protected lungs against damage from hyperoxia, presumably by preventing the activation of NOX2 and the amplification of lung injury associated with inflammation. These findings demonstrate that MJ33, a potent inhibitor of Prdx6 PLA2 activity, can protect mouse lungs against the manifestations of acute lung injury due to oxidative stress. PMID:25637741

  13. Pressure Modulation of the Enzymatic Activity of Phospholipase A2, A Putative Membrane-Associated Pressure Sensor.

    PubMed

    Suladze, Saba; Cinar, Suleyman; Sperlich, Benjamin; Winter, Roland

    2015-10-01

    Phospholipases A2 (PLA2) catalyze the hydrolysis reaction of sn-2 fatty acids of membrane phospholipids and are also involved in receptor signaling and transcriptional pathways. Here, we used pressure modulation of the PLA2 activity and of the membrane's physical-chemical properties to reveal new mechanistic information about the membrane association and subsequent enzymatic reaction of PLA2. Although the effect of high hydrostatic pressure (HHP) on aqueous soluble and integral membrane proteins has been investigated to some extent, its effect on enzymatic reactions operating at the water/lipid interface has not been explored, yet. This study focuses on the effect of HHP on the structure, membrane binding and enzymatic activity of membrane-associated bee venom PLA2, covering a pressure range up to 2 kbar. To this end, high-pressure Fourier-transform infrared and high-pressure stopped-flow fluorescence spectroscopies were applied. The results show that PLA2 binding to model biomembranes is not significantly affected by pressure and occurs in at least two kinetically distinct steps. Followed by fast initial membrane association, structural reorganization of α-helical segments of PLA2 takes place at the lipid water interface. FRET-based activity measurements reveal that pressure has a marked inhibitory effect on the lipid hydrolysis rate, which decreases by 75% upon compression up to 2 kbar. Lipid hydrolysis under extreme environmental conditions, such as those encountered in the deep sea where pressures up to the kbar-level are encountered, is hence markedly affected by HHP, rendering PLA2, next to being a primary osmosensor, a good candidate for a sensitive pressure sensor in vivo.

  14. GS/DBM/PLA porous composite biomaterial for the treatment of infective femoral condyle defect in rats

    PubMed Central

    LIU, XIAOMING; YANG, LIN; LI, JING; ZHANG, YUMING; XU, WEIJUN; REN, YAN; LIU, BIWANG; YANG, BIAO; LI, BAOXING

    2016-01-01

    A bone defect resulting from open bone trauma may easily become infected; however, the administration of efficacious systemic antibiotics cannot be performed at safe levels. Previous studies have investigated anti-infective biomaterials that incorporate into bone and facilitate the direct application of high-concentration local antibiotics. In the present study, the effect of a novel porous composite with gentamicin sulfate (GS) in treating infected femoral condyle defects was investigated using a rat model. A novel porous composite biomaterial was prepared based on a supercritical carbon dioxide fluid technique that combined GS, demineralized bone matrix (DBM) and polylactic acid (PLA). A rat femoral condyle fracture model of infection was established. The GS/DBM/PLA composite biomaterial was implanted and its physicochemical characteristics, biocompatibility and ability to facilitate repair of infected bone defect were assessed. The GS/DBM/PLA composite biomaterial maintained the antibiotic activity of GS, with good anti-compression strength, porosity and biocompatibility. The results of the animal experiments indicated that the GS/DBM/PLA composite biomaterial exerted marked anti-infective effects and facilitated bone defect repair, while simultaneously controlling infection. Porous GS/DBM/PLA is therefore a promising composite biomaterial for use in bone tissue engineering. PMID:27284292

  15. Tailored delivery of active keratinocyte growth factor from biodegradable polymer formulations.

    PubMed

    Cho, Eun Jeong; Tao, Zunyu; Tang, Ying; Tehan, Elizabeth C; Bright, Frank V; Hicks, Wesley L; Gardella, Joseph A; Hard, Robert

    2003-08-01

    We report the results of a high throughput screening campaign that is aimed to develop a biodegradable polymer-based formulation to deliver active keratinocyte growth factor (KGF) and provide a means to tune the KGF delivery rate. A statistical design strategy was used to prepare and screen a series of polymer blends that were composed of poly(lactic acid) (PLA), poly(glycolic acid) (PGA), and the surfactant sodium bis(ethylhexyl)sulfosuccinate (Aerosol-OT, AOT). Chloroform was the solvent. Our high throughput screening method used a two-tiered assessment strategy. At Level 1, we identified "lead" KFG-loaded formulations that exhibited KGF emission spectra that were the most similar to the native KGF spectrum recorded in buffer. At Level 2, we used steady-state emission and a homogeneous polarization immunoassay strategy to determine the concentration of total and active KGF, respectively, liberated from the lead formulations during biodegradation. After preparing and screening 2500 formulations, we identified several viable, lead formulations. An analysis of the data showed that the combination of PLA, PGA, and AOT were important to yield a high fraction of active KGF upon release from the formulation; no combination of any two together produced an effect as good as the ternary formulation. The optimum formulations that yielded the highest fraction of active KGF upon release had the following general features: PLA/PGA (w/w) near unity, AOT loading of 100-200 mM, water/AOT mole ratio of 10-20, and a pH between 6 and 8. PLA alone cast from chloroform delivered KGF, but that KGF did not bind to anti-KGF antibodies (i.e., it was inactive). We can tune the KGF release kinetics by more than two orders of magnitude while maintaining the KGF activity upon liberation from the formulation by adjusting the PLA molecular weight.

  16. Mechanism of Cytosolic Phospholipase A(2) Activation in Ghrelin Protection of Salivary Gland Acinar Cells against Ethanol Cytotoxicity.

    PubMed

    Slomiany, Bronislaw L; Slomiany, Amalia

    2010-01-01

    Ghrelin, a peptide hormone, newly identified in oral mucosal tissues, has emerged recently as an important mediator of the processes of mucosal defense. Here, we report on the mechanism of ghrelin protection against ethanol cytotoxicity in rat sublingual salivary gland cells. The protective effect of ghrelin was associated with the increase in NO and PGE2, and upregulation in cytosolic phospholipase A(2) (cPLA(2)) activity and arachidonic acid (AA) release. The loss in countering effect of ghrelin occurred with cNOS inhibitor, L-NAME, as well as indomethacin and COX-1 inhibitor, SC-560, while COX-2 inhibitor, NS-398, and iNOS inhibitor, 1400W, had no effect. The effect of L-NAME was reflected in the inhibition of ghrelin-induced cell capacity for NO production, cPLA(2) activation and PGE2 generation, whereas indomethacin caused only the inhibition in PGE2. Moreover, the ghrelin-induced up-regulation in AA release was reflected in the cPLA(2) phosphorylation and S-nitrosylation. Inhibition in ghrelin-induced S-nitrosylation was attained with L-NAME, whereas the ERK inhibitor, PD98059, caused the blockage in cPLA(2) protein phosphorylation as well as S-nitrosylation. Thus, ghrelin protection of salivary gland cells against ethanol involves cNOS-derived NO induction of cPLA(2) activation through S-nitrosylation for the increase in AA release at the site of COX-1 action for PGE2 synthesis.

  17. Mitochondria from a mouse model of the human infantile neuroaxonal dystrophy (INAD) with genetic defects in VIA iPLA2 have disturbed Ca(2+) regulation with reduction in Ca(2+) capacity.

    PubMed

    Strokin, Mikhail; Reiser, Georg

    2016-10-01

    Mutations in the PLA2G6 gene which encodes Ca(2+)-independent phospholipase A2 (VIA iPLA2) were detected in 85% of cases of the inherited degenerative nervous system disorder INAD (infantile neuroaxonal dystrophy, OMIM #256600). However, molecular mechanisms linking these mutations to the disease progression are unclear. VIA iPLA2 is expressed also in mitochondria. Here, we investigate Ca(2+) handling by brain mitochondria derived from mice with hypomorph Pla2g6 allele. These animals with reduced transcript levels (5% of wild type) represent a suitable model for INAD. We demonstrated significant reduction of Ca(2+) uptake rate and Ca(2+) retention capacity in brain mitochondria isolated from this mutant. This phenotype could be mimicked when in wild-type controls VIA iPLA2 was inhibited by S-BEL. Importantly, the reduction could be ameliorated partly by addition of the VIA iPLA2 product, sn-2 lysophosphatidyl-choline. Furthermore, we demonstrated in situ a reduced mitochondrial potential in neurons from mice deficient in VIA iPLA2, which could cause the reduced Ca(2+) uptake rate via the potential-dependent mitochondrial Ca(2+) uniporter. Thus, the disturbances in mitochondrial potential and the changes in Ca(2+) handling were dependent on VIA iPLA2 activity. Reduced mitochondrial Ca(2+) uptake rate and Ca(2+) retention capacity might result in increased vulnerability of mitochondria to the Ca(2+) overload and in disturbed cellular Ca(2+) signaling during INAD. For VIA iPLA2, non-canonical functions beyond sole phospholipid turnover seem to be important, such as regulation of store-operated Ca(2+) entry in cells. Thus, our findings bring new insight into molecular mechanism affected in INAD and highlight the non-canonical function of VIA iPLA2 in regulation of mitochondrial Ca(2+) handling.

  18. Peroxiredoxin 6: A Bifunctional Enzyme with Glutathione Peroxidase and Phospholipase A2 Activities

    PubMed Central

    2011-01-01

    Abstract Peroxiredoxin 6 (Prdx6) is the prototype and the only mammalian 1-Cys member of the Prdx family. Major differences from 2-Cys Prdxs include the use of glutathione (GSH) instead of thioredoxin as the physiological reductant, heterodimerization with πGSH S-transferase as part of the catalytic cycle, and the ability either to reduce the oxidized sn-2 fatty acyl group of phospholipids (peroxidase activity) or to hydrolyze the sn-2 ester (alkyl) bond of phospholipids (phospholipase A2 [PLA2] activity). The bifunctional protein has separate active sites for peroxidase (C47, R132, H39) and PLA2 (S32, D140, H26) activities. These activities are dependent on binding of the protein to phospholipids at acidic pH and to oxidized phospholipids at cytosolic pH. Prdx6 can be phosphorylated by MAP kinases at T177, which markedly increases its PLA2 activity and broadens its pH-activity spectrum. Prdx6 is primarily cytosolic but also is targeted to acidic organelles (lysosomes, lamellar bodies) by a specific targeting sequence (amino acids 31–40). Oxidant stress and keratinocyte growth factor are potent regulators of Prdx6 gene expression. Prdx6 has important roles in both antioxidant defense based on its ability to reduce peroxidized membrane phospholipids and in phospholipid homeostasis based on its ability to generate lysophospholipid substrate for the remodeling pathway of phospholipid synthesis. Antioxid. Redox Signal. 15, 831–844. PMID:20919932

  19. Biological and biochemical characterization of two new PLA2 isoforms Cdc-9 and Cdc-10 from Crotalus durissus cumanensis snake venom.

    PubMed

    Romero-Vargas, Frey Francisco; Ponce-Soto, Luis Alberto; Martins-de-Souza, Daniel; Marangoni, Sergio

    2010-01-01

    This work reports the purification, biological characterization and amino acid sequence of two new basic PLA(2) isoforms, Cdc-9 and Cdc-10, purified from the Crotalus durissus cumanensis venom by one step analytical chromatography reverse phase HPLC. The molecular masses of the PLA(2) were 14,175+/-2.7 Da for Cdc-9 and 14,228+/-3.5 Da for Cdc-10 both deduced by primary structure and confirmed by MALDI-TOF. The isoforms presented an amino acid sequence of 122 amino acid residues, being Cdc-9: SLVQFNKMIK FETRKSGLPF YAAYGCYCGW GGQRPKDATD RCCFVHDCCY GKVAKCNTKW DIYSYSLKSG YITCGKGTWC KEQICECDRV AAECLRRSLS TYKNEYMFYP DSRCREPPEY TC with pI value of 8.25 and Cdc-10: SLLQFNKMIK FETRKSGVPF YAAYGCYCGW GGRRPKDPTD RCCFVHDCCY GKLTKCNTKW DIYSYSLKSG YITCGKGTWC KEQICECDRV AAECLRRSLN TYKNEYMFYP DSRCRGPPEY TC with a pI value of 8.46, showing highly conserved Ca(2+)-binding and catalytic sites. The PLA(2) activity decreased when the isoforms Cdc-9 and Cdc-10 were incubated with 4-bromophenacyl bromide (p-BPB), anhydrous acetic acid and p-nitrobenzene sulfonyl fluoride (NBSF) when compared with the activity of both native isoforms. In mice, the PLA(2) isoforms Cdc-9 and Cdc-10 induced myonecrosis and edema. Myotoxic and edema activities were reduced after treatment of the isoforms with p-BPB; acetylation of the lysine residues and the treatment of PLA(2) with NBSF have also induced edema reduction. However, p-BPB strongly diminishes the local and systemic myotoxic effects.

  20. Crystallization and preliminary X-ray diffraction analysis of a myotoxic Lys49-PLA{sub 2} from Bothrops jararacussu venom complexed with p-bromophenacyl bromide

    SciTech Connect

    Marchi-Salvador, D. P.; Fernandes, C. A. H.; Amui, S. F.; Soares, A. M.

    2006-06-01

    A non-catalytic and myotoxic Lys49-PLA{sub 2} from B. jararacussu venom was crystallized with BPB inhibitor and X-ray diffraction data were collected. Preliminary analysis indicates that the ligand is bound to the His48 residue. Structure determination may provide insights into the myotoxic and cytotoxic mechanisms of Lys49-PLA{sub 2}s. For the first time, a non-catalytic and myotoxic Lys49-PLA{sub 2} (BthTX-I from Bothrops jararacussu venom) has been crystallized with BPB inhibitor. X-ray diffraction data were collected and electron-density calculations showed that the ligand is bound to the His48 residue. BthTX-I with His48 chemically modified by BPB shows strongly reduced myotoxic and cytotoxic activities. This suggests a biological correlation between the modification of His48, which is associated with catalytic activity of PLA{sub 2}s, and other toxicological activities of Lys49-PLA{sub 2}s.

  1. Development of PLA films containing oregano essential oil (Origanum vulgare L. virens) intended for use in food packaging.

    PubMed

    Llana-Ruiz-Cabello, M; Pichardo, S; Bermúdez, J M; Baños, A; Núñez, C; Guillamón, E; Aucejo, S; Cameán, A M

    2016-08-01

    Consumers' concerns about the environment and health have led to the development of new food packaging materials avoiding petroleum-based matrices and synthetic additives. The present study has developed polylactic acid (PLA) films containing different concentrations of essential oil from Origanum vulgare L. virens (OEO). The effectiveness of this new active packaging was checked for use in ready-to-eat salads. A plasticising effect was observed when OEO was incorporated in PLA films. The rest of the mechanical and physical properties of developed films did not show much change when OEO was included in the film. An antioxidant effect was recorded only for films containing the highest percentages of the active agent (5% and 10%). In addition, films exhibited in vitro antibacterial activity against Staphylococcus aureus, Yersinia enterocolitica, Listeria monocytogenes, Enterococcus faecalis and Staphylococcus carnosus. Moreover, in ready-to-eat salads, antimicrobial activity was only observed against yeast and moulds, where 5% and 10% of OEO was the most effective.

  2. Virucidal activity of an activated sludge supernatant.

    PubMed

    Rehn, Y; Schwartzbrod, L

    1993-09-01

    The virucidal activity of the activated sludge aqueous phase was studied from the time of initial inoculation with a poliovirus type 1 suspension and for durations of three and nine days. The mixtures were incubated in presence of a nutritive medium at 26 degrees C and samples were drawn at regular intervals of time for viral titration. The activated sludge supernatant (ASS) caused an important decrease of the titer of the poliovirus type 1 suspension especially after nine days of incubation. There was an average reduction of the viral titer of 79% after three days and 97% after nine days. When incubating the ASS with a nutritive medium before inoculating it, the viral decrease was much greater than when incubating without nutritive medium. When sterilizing the ASS before incubation and then inoculating it, no significant virucidal activity was observed (0% to 6%). Furthermore, when the ASS was subjected to a sterilization by filtration after incubation and was then inoculated, there existed a lower but not negligible viral inactivation (53% to 64%). The virucidal activity potentiality of the ASS is therefore due to microorganisms acting both directly as a support for viral particles adsorption and indirectly via the synthesis of substances with virucidal activity. When freezing and thawing the incubated ASS, and then sterilizing it by filtration before inoculation, the viral decrease reached 87% to 94%. This proves that the virucidal substances are only partly excreted by the microorganisms.

  3. Antiviral Activity of Glycyrrhizin against Hepatitis C Virus In Vitro

    PubMed Central

    Matsumoto, Yoshihiro; Matsuura, Tomokazu; Aoyagi, Haruyo; Matsuda, Mami; Hmwe, Su Su; Date, Tomoko; Watanabe, Noriyuki; Watashi, Koichi; Suzuki, Ryosuke; Ichinose, Shizuko; Wake, Kenjiro; Suzuki, Tetsuro; Miyamura, Tatsuo; Wakita, Takaji; Aizaki, Hideki

    2013-01-01

    Glycyrrhizin (GL) has been used in Japan to treat patients with chronic viral hepatitis, as an anti-inflammatory drug to reduce serum alanine aminotransferase levels. GL is also known to exhibit various biological activities, including anti-viral effects, but the anti-hepatitis C virus (HCV) effect of GL remains to be clarified. In this study, we demonstrated that GL treatment of HCV-infected Huh7 cells caused a reduction of infectious HCV production using cell culture-produced HCV (HCVcc). To determine the target step in the HCV lifecycle of GL, we used HCV pseudoparticles (HCVpp), replicon, and HCVcc systems. Significant suppressions of viral entry and replication steps were not observed. Interestingly, extracellular infectivity was decreased, and intracellular infectivity was increased. By immunofluorescence and electron microscopic analysis of GL treated cells, HCV core antigens and electron-dense particles had accumulated on endoplasmic reticulum attached to lipid droplet (LD), respectively, which is thought to act as platforms for HCV assembly. Furthermore, the amount of HCV core antigen in LD fraction increased. Taken together, these results suggest that GL inhibits release of infectious HCV particles. GL is known to have an inhibitory effect on phospholipase A2 (PLA2). We found that group 1B PLA2 (PLA2G1B) inhibitor also decreased HCV release, suggesting that suppression of virus release by GL treatment may be due to its inhibitory effect on PLA2G1B. Finally, we demonstrated that combination treatment with GL augmented IFN-induced reduction of virus in the HCVcc system. GL is identified as a novel anti-HCV agent that targets infectious virus particle release. PMID:23874843

  4. Active magnetic regenerator

    DOEpatents

    Barclay, John A.; Steyert, William A.

    1982-01-01

    The disclosure is directed to an active magnetic regenerator apparatus and method. Brayton, Stirling, Ericsson, and Carnot cycles and the like may be utilized in an active magnetic regenerator to provide efficient refrigeration over relatively large temperature ranges.

  5. Preschoolers’ Physical Activity Behaviours

    PubMed Central

    Irwin, Jennifer D.; He, Meizi; Bouck, L. Michelle Sangster; Tucker, Patricia; Pollett, Graham L.

    2016-01-01

    Objectives To understand parents’ perspectives of their preschoolers’ physical activity behaviours. Methods A maximum variation sample of 71 parents explored their preschoolers’ physical activity behaviours through 10 semi-structured focus group discussions. Results Parents perceived Canada’s Physical Activity Guidelines for Children as inadequate; that their preschoolers get and need more than 30–90 minutes of activity daily; and that physical activity habits must be established during the preschool years. Nine barriers against and facilitators toward adequate physical activity were proposed: child’s age, weather, daycare, siblings, finances, time, society and safety, parents’ impact, and child’s activity preferences. Discussion The need for education and interventions that address current barriers are essential for establishing physical activity as a lifestyle behaviour during early childhood and, consequently, helping to prevent both childhood and adulthood obesity. PMID:16625802

  6. Balance Food and Activity

    MedlinePlus

    ... For Health Professionals Tools and Resources Promotional Materials Programming Materials Weight Management Nutrition Physical Activity Reduce Screen ... Training For Health Professionals Tools & Resources Promotional ... Programming Materials Weight Management Nutrition Physical Activity Reduce Screen ...

  7. Population Education. Awareness Activities.

    ERIC Educational Resources Information Center

    Brouse, Deborah E.

    1990-01-01

    Described are awareness activities that deal with human population growth, resources, and the environment. Activities include simulations, mathematical exercises, and discussions of the topic. Specific examples of what individuals can do to help are listed. (KR)

  8. Major operations and activities

    SciTech Connect

    Black, D.G.

    1995-06-01

    This section of the 1994 Hanford Site Environmental Report summarizes the major operations and activities on the site. These operations and activities include site management, waste management, environmental restoration and corrective actions, and research and technology development.

  9. Active Fire Mapping Program

    MedlinePlus

    ... Incidents (Home) New Large Incidents Fire Detection Maps MODIS Satellite Imagery VIIRS Satellite Imagery Fire Detection GIS ... Data Web Services Latest Detected Fire Activity Other MODIS Products Frequently Asked Questions About Active Fire Maps ...

  10. Family Activities for Fitness

    ERIC Educational Resources Information Center

    Grosse, Susan J.

    2009-01-01

    This article discusses how families can increase family togetherness and improve physical fitness. The author provides easy ways to implement family friendly activities for improving and maintaining physical health. These activities include: walking, backyard games, and fitness challenges.

  11. Green Schools Activity Booklet.

    ERIC Educational Resources Information Center

    Sacramento Tree Foundation, CA.

    This collection of interdisciplinary hands-on activities covers a variety of topics related to trees and conservation. Twenty-four activities integrate the subjects of social studies, fine arts, science, language arts, math, geography, and music. Although activity instructions are not consistent they usually contain details on objectives and…

  12. Activity Sheets. Draft Copy.

    ERIC Educational Resources Information Center

    Duke Power Company, Educational Services Dept., Charlotte, NC.

    This document consists of energy vocabulary activities, three games, worksheets, laboratory activities/exercises, and an introductory classroom exercise designed to introduce energy concepts to students. Vocabulary activities focus on coal and energy consumption. The three games (with instructions) focus on various aspects of energy and energy…

  13. Bonus Activity Book.

    ERIC Educational Resources Information Center

    Learning, 1992

    1992-01-01

    Provides on-task activities to fill in unexpected extra moments in elementary classes. The activities require little preparation and take 5-15 minutes to complete. There are activities for math, language arts, social science, science, critical thinking, and computer. An outer space board game is also included. (SM)

  14. Climate Change: An Activity.

    ERIC Educational Resources Information Center

    Lewis, Garry

    1995-01-01

    Presents a segment of the Geoscience Education booklet, Climate Change, that contains information and activities that enable students to gain a better appreciation of the possible effects human activity has on the Earth's climate. Describes the Terrace Temperatures activity that leads students through an investigation using foraminifera data to…

  15. Active Learning Crosses Generations.

    ERIC Educational Resources Information Center

    Woodard, Diane K.

    2002-01-01

    Describes the benefits of intergenerational programs, highlighting a child care program that offers age-appropriate and mutually beneficial activities for children and elders within a nearby retirement community. The program has adopted High/Scope's active learning approach to planning and implementing activities that involve both generations. The…

  16. Activity Theory and Ontology

    ERIC Educational Resources Information Center

    Peim, Nick

    2009-01-01

    This paper seeks to re-examine Yrio Engestrom's activity theory as a technology of knowledge designed to enable positive transformations of specific practices. The paper focuses on a key paper where Engestrom defines the nature and present state of activity theory. Beginning with a brief account of the relations between activity theory and…

  17. Highlights of 1981 activities

    NASA Technical Reports Server (NTRS)

    1981-01-01

    The highlights of NASA's 1981 activities are presented, including the results of the two flights of the space shuttle Columbia and the Voyager 2 encounter with Saturn. Accomplishments in the areas of space transportation operations; space science; aeronautical, energy, and space research and development; as well as space tracking, international activities, and 1981 launch activities are discussed.

  18. Measurement of Physical Activity.

    ERIC Educational Resources Information Center

    Dishman, Rod K.; Washburn, Richard A.; Schoeller, Dale A.

    2001-01-01

    Valid assessment of physical activity must be unobtrusive, practical to administer, and specific about physical activity type, frequency, duration, and intensity. Assessment methods can be categorized according to whether they provide direct or indirect (e.g., self-report) observation of physical activity, body motion, physiological response…

  19. FL Activities & Festivals.

    ERIC Educational Resources Information Center

    American Council on the Teaching of Foreign Languages, Hastings-on-Hudson, NY.

    A collection of student, class, and school foreign language activities suggests a variety of projects and describes three specific school efforts. The suggested activities include: (1) individual student efforts such as writing to pen-pals; (2) group activities such as a foreign language auction or sing-along; (3) group projects for the school…

  20. Technology Learning Activities I.

    ERIC Educational Resources Information Center

    International Technology Education Association, Reston, VA.

    This guide contains 30 technology learning activities. Activities may contain all or some of the following: an introduction, objectives, materials and equipment, challenges, limitations, notes and investigations, resources and references used, and evaluation ideas. Activity titles are: (1) Occupations in Construction Technology; (2) Designing a…

  1. Woodsy Owl Activity Guide.

    ERIC Educational Resources Information Center

    Forest Service (USDA), Washington, DC.

    This guide offers teachers and after-school group leaders 12 fun and engaging activities. Activities feature lessons on trees, water, wind, the earth, food, and waste. The activities are designed to help children aged 5-8 become more aware of the natural environment and fundamental conservation principles. Titles of children's books are embedded…

  2. WHCLIS Goals vs. PLA Roles.

    ERIC Educational Resources Information Center

    Durrance, Joan C.; Allen, Catherine

    1991-01-01

    Explores the relationship between Public Library Association (PLA) planning and the themes of literacy, productivity, and democracy that were chosen by the White House Conference on Library and Information Services (WHCLIS). Discussion is based on data collected by the Public Library Data Service (PLDS) that examine current library services in…

  3. Design of 1-arylsulfamido-2-alkylpiperazine derivatives as secreted PLA2 inhibitors.

    PubMed

    Badrinarayan, Preethi; Srivani, P; Narahari Sastry, G

    2011-04-01

    Structure and analog based analysis of 3D-QSAR, CoMFA and CoMSIA, along with different docking protocols were used to evaluate the structure activity relationship of 26 analogues of 1-aryl sulfamido-2-alkyl piperazines to model the activities of group I and II secreted phospholipases A(2) (sPLA(2)s) and probe into the chemical space and nature of receptor--ligand interactions. The best CoMFA model yields cross-validated (q(2)) and conventional correlation coefficients (r(2)) of 0.703 and 0.962 respectively whereas CoMSIA model yields q(2) and r(2) values of 0.408 and 0.922 respectively, followed by docking analysis using FlexX and GOLD methodologies on the X-ray structure of human and bovine PLA(2)s. A comparative study was made to find out the differences in the active site residues of both PLA(2)s. The information enunciated from the analysis of CoMFA and CoMSIA maps and docking results were analyzed and employed in the design of 29 new ligands using molecules 4, 21, 22 from the initial set as templates. New ligands for group I and II secreted phospholipases A(2) (sPLA(2)s) have been thus designed based on the 32 analogues of 1-aryl sulfamido-2-alkyl piperazine with a cursory note on its synthetic feasibility. Molecular modeling studies indicate that the newly designed ligands are expected to show high affinity and experimental efforts in this direction is highly rewarding. PMID:20571844

  4. Creating a Positive PLA Experience: A Step-by-Step Look at University PLA

    ERIC Educational Resources Information Center

    Leiste, Sara M.; Jensen, Kathryn

    2011-01-01

    A prior learning assessment (PLA) can be an intimidating process for adult learners. Capella University's PLA team has developed best practices, resources, and tools to foster a positive experience and to remove barriers in PLA and uses three criteria to determine how to best administer the assessment. First, a PLA must be motivating, as described…

  5. Activation of J77A.1 Macrophages by Three Phospholipases A2 Isolated from Bothrops atrox Snake Venom

    PubMed Central

    Furtado, Juliana L.; Oliveira, George A.; Pontes, Adriana S.; Setúbal, Sulamita da S.; Xavier, Caroline V.; Lacouth-Silva, Fabianne; Lima, Beatriz F.; Zaqueo, Kayena D.; Kayano, Anderson M.; Calderon, Leonardo A.; Stábeli, Rodrigo G.; Soares, Andreimar M.; Zuliani, Juliana P.

    2014-01-01

    In the present study, we investigated the in vitro effects of two basic myotoxic phospholipases A2 (PLA2), BaTX-I, a catalytically inactive Lys-49 variant, and BaTX-II, a catalytically active Asp-49, and of one acidic myotoxic PLA2, BaPLA2, a catalytically active Asp-49, isolated from Bothrops atrox snake venom, on the activation of J774A.1 macrophages. At noncytotoxic concentrations, the toxins did not affect the adhesion of the macrophages, nor their ability to detach. The data obtained showed that only BaTX-I stimulated complement receptor-mediated phagocytosis. However, BaTX-I, BaTX-II, and BaPLA2 induced the release of the superoxide anion by J774A.1 macrophages. Additionally, only BaTX-I raised the lysosomal volume of macrophages after 15 min of incubation. After 30 min, all the phospholipases increased this parameter, which was not observed within 60 min. Moreover, BaTX-I, BaTX-II, and BaPLA2 increased the number of lipid bodies on macrophages submitted to phagocytosis and not submitted to phagocytosis. However, BaTX-II and BaPLA2 induced the release of TNF-α by J774A.1 macrophages. Taken together, the data show that, despite differences in enzymatic activity, the three toxins induced inflammatory events and whether the enzyme is acidic or basic does not seem to contribute to these effects. PMID:24592395

  6. Activation of J77A.1 macrophages by three phospholipases A2 isolated from Bothrops atrox snake venom.

    PubMed

    Furtado, Juliana L; Oliveira, George A; Pontes, Adriana S; Setúbal, Sulamita da S; Xavier, Caroline V; Lacouth-Silva, Fabianne; Lima, Beatriz F; Zaqueo, Kayena D; Kayano, Anderson M; Calderon, Leonardo A; Stábeli, Rodrigo G; Soares, Andreimar M; Zuliani, Juliana P

    2014-01-01

    In the present study, we investigated the in vitro effects of two basic myotoxic phospholipases A2 (PLA2), BaTX-I, a catalytically inactive Lys-49 variant, and BaTX-II, a catalytically active Asp-49, and of one acidic myotoxic PLA2, BaPLA2, a catalytically active Asp-49, isolated from Bothrops atrox snake venom, on the activation of J774A.1 macrophages. At noncytotoxic concentrations, the toxins did not affect the adhesion of the macrophages, nor their ability to detach. The data obtained showed that only BaTX-I stimulated complement receptor-mediated phagocytosis. However, BaTX-I, BaTX-II, and BaPLA2 induced the release of the superoxide anion by J774A.1 macrophages. Additionally, only BaTX-I raised the lysosomal volume of macrophages after 15 min of incubation. After 30 min, all the phospholipases increased this parameter, which was not observed within 60 min. Moreover, BaTX-I, BaTX-II, and BaPLA2 increased the number of lipid bodies on macrophages submitted to phagocytosis and not submitted to phagocytosis. However, BaTX-II and BaPLA2 induced the release of TNF-α by J774A.1 macrophages. Taken together, the data show that, despite differences in enzymatic activity, the three toxins induced inflammatory events and whether the enzyme is acidic or basic does not seem to contribute to these effects. PMID:24592395

  7. Tea enhances insulin activity.

    PubMed

    Anderson, Richard A; Polansky, Marilyn M

    2002-11-20

    The most widely known health benefits of tea relate to the polyphenols as the principal active ingredients in protection against oxidative damage and in antibacterial, antiviral, anticarcinogenic, and antimutagenic activities, but polyphenols in tea may also increase insulin activity. The objective of this study was to determine the insulin-enhancing properties of tea and its components. Tea, as normally consumed, was shown to increase insulin activity >15-fold in vitro in an epididymal fat cell assay. Black, green, and oolong teas but not herbal teas, which are not teas in the traditional sense because they do not contain leaves of Camellia senensis, were all shown to increase insulin activity. High-performance liquid chromatography fractionation of tea extracts utilizing a Waters SymmetryPrep C18 column showed that the majority of the insulin-potentiating activity for green and oolong teas was due to epigallocatechin gallate. For black tea, the activity was present in several regions of the chromatogram corresponding to, in addition to epigallocatechin gallate, tannins, theaflavins, and other undefined compounds. Several known compounds found in tea were shown to enhance insulin with the greatest activity due to epigallocatechin gallate followed by epicatechin gallate, tannins, and theaflavins. Caffeine, catechin, and epicatechin displayed insignificant insulin-enhancing activities. Addition of lemon to the tea did not affect the insulin-potentiating activity. Addition of 5 g of 2% milk per cup decreased the insulin-potentiating activity one-third, and addition of 50 g of milk per cup decreased the insulin-potentiating activity approximately 90%. Nondairy creamers and soy milk also decreased the insulin-enhancing activity. These data demonstrate that tea contains in vitro insulin-enhancing activity and the predominant active ingredient is epigallocatechin gallate. PMID:12428980

  8. Activation of phospholipase A{sub 2} in 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine liposomes containing lipid ozonation products

    SciTech Connect

    Salgo, M.G.; Squadrito, G.L.; Pryor, W.A.

    1994-05-01

    The activation of phospholipase A{sub 2} (PLA{sub 2}) by lipid ozonation products is reported. The principal products from the ozonation of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) are 1-palmitoyl-2-[8-3(5-octyl-1,2,4-trioxolan-3-yl)octanoyl]--sn-glycero-3-phosphocholine (PC-Criegee ozonide) and 1-palmitoyl-2-(9-oxononanoyl)-sn-glycero-3-phosphocholine (PC-aldehyde). Here we test the hypothesis that these two compounds are mediators of ozone toxicity. Using POPC vesicles, we find that PLA{sub 2} recognizes and hydrolyzes PC-Criegee ozonide at the same rate as that of arachidonic acid. Although the PC-aldehyde is not a substrate for PLA{sub 2}, the enzymatic rate of hydrolysis by PLA{sub 2} of unaltered fatty acids incorporated into POPC is enhanced when PC-aldehyde is present in the bilayer. Thus, both PC-Criegee ozonide and PC-aldehyde alter the activity of PLA{sub 2}, perhaps via an effect on membrane packing order. The capacity of PLA{sub 2} to recognize the PC-Criegee, and therefore ozone-induced damage, suggests a detoxification property of the enzyme and also a role in maintaining the structural properties of bilayer membranes that have been altered by exposure to ozone. 29 refs., 3 figs., 1 tab.

  9. Vestibular activation of sympathetic nerve activity

    NASA Technical Reports Server (NTRS)

    Ray, C. A.; Carter, J. R.

    2003-01-01

    AIM: The vestibulosympathetic reflex refers to sympathetic nerve activation by the vestibular system. Animal studies indicate that the vestibular system assists in blood pressure regulation during orthostasis. Although human studies clearly demonstrate activation of muscle sympathetic nerve activity (MSNA) during engagement of the otolith organs, the role of the vestibulosympathetic reflex in maintaining blood pressure during orthostasis is not well-established. Examination of the vestibulosympathetic reflex with other cardiovascular reflexes indicates that it is a powerful and independent reflex. Ageing, which is associated with an increased risk for orthostatic hypotension, attenuates the vestibulosympathetic reflex. The attenuated reflex is associated with a reduction in arterial pressure. CONCLUSION: These findings suggest that the vestibulosympathetic reflex assists in blood pressure regulation in humans, but future studies examining this reflex in other orthostatically intolerant populations are necessary to address this hypothesis.

  10. Botanical Polyphenols Mitigate Microglial Activation and Microglia-Induced Neurotoxicity: Role of Cytosolic Phospholipase A2.

    PubMed

    Chuang, Dennis Y; Simonyi, Agnes; Cui, Jiankun; Lubahn, Dennis B; Gu, Zezong; Sun, Grace Y

    2016-09-01

    Microglia play a significant role in the generation and propagation of oxidative/nitrosative stress, and are the basis of neuroinflammatory responses in the central nervous system. Upon stimulation by endotoxins such as lipopolysaccharides (LPS), these cells release pro-inflammatory factors which can exert harmful effects on surrounding neurons, leading to secondary neuronal damage and cell death. Our previous studies demonstrated the effects of botanical polyphenols to mitigate inflammatory responses induced by LPS, and highlighted an important role for cytosolic phospholipase A2 (cPLA2) upstream of the pro-inflammatory pathways (Chuang et al. in J Neuroinflammation 12(1):199, 2015. doi: 10.1186/s12974-015-0419-0 ). In this study, we investigate the action of botanical compounds and assess whether suppression of cPLA2 in microglia is involved in the neurotoxic effects on neurons. Differentiated SH-SY5Y neuroblastoma cells were used to test the neurotoxicity of conditioned medium from stimulated microglial cells, and WST-1 assay was used to assess for the cell viability of SH-SY5Y cells. Botanicals such as quercetin and honokiol (but not cyanidin-3-O-glucoside, 3CG) were effective in inhibiting LPS-induced nitric oxide (NO) production and phosphorylation of cPLA2. Conditioned medium from BV-2 cells stimulated with LPS or IFNγ caused neurotoxicity to SH-SY5Y cells. Decrease in cell viability could be ameliorated by pharmacological inhibitors for cPLA2 as well as by down-regulating cPLA2 with siRNA. Botanicals effective in inhibition of LPS-induced NO and cPLA2 phosphorylation were also effective in ameliorating microglial-induced neurotoxicity. Results demonstrated cytotoxic factors from activated microglial cells to cause damaging effects to neurons and potential use of botanical polyphenols to ameliorate the neurotoxic effects. PMID:27339657

  11. Phospholipase A(2) activation by poultry particulate matter is mediated through extracellular signal-regulated kinase in lung epithelial cells: regulation of interleukin-8 release.

    PubMed

    Kotha, Sainath R; Piper, Melissa G; Patel, Rishi B; Sliman, Sean; Malireddy, Smitha; Zhao, Lingying; Baran, Christopher P; Nana-Sinkam, Patrick S; Wewers, Mark D; Romberger, Debra; Marsh, Clay B; Parinandi, Narasimham L

    2013-11-01

    The mechanisms of poultry particulate matter (PM)-induced agricultural respiratory disorders are not thoroughly understood. Hence, it is hypothesized in this article that poultry PM induces the release of interleukin-8 (IL-8) by lung epithelial cells that is regulated upstream by the concerted action of cytosolic phospholipase A2 (cPLA2) and extracellular signal-regulated kinase (ERK). To test this hypothesis, the widely used cultured human lung epithelial cells (A549) were chosen as the model system. Poultry PM caused a significant activation of PLA2 in A549 cells, which was attenuated by AACOCF3 (cPLA2 inhibitor) and PD98059 (ERK-1/2 upstream inhibitor). Poultry PM induced upstream ERK-1/2 phosphorylation and downstream cPLA2 serine phosphorylation, in a concerted fashion, in cells with enhanced association of ERK-1/2 and cPLA2. The poultry PM-induced cPLA2 serine phosphorylation and IL-8 release were attenuated by AACOCF3, PD98059, and by transfection with dominant-negative ERK-1/2 DNA in cells. The poultry PM-induced IL-8 release by the bone marrow-derived macrophages of cPLA2 knockout mice was significantly lower. For the first time, this study demonstrated that the poultry PM-induced IL-8 secretion by human lung epithelial cells was regulated by cPLA2 activation through ERK-mediated serine phosphorylation, suggesting a mechanism of airway inflammation among poultry farm workers.

  12. When functionalization of PLA surfaces meets Thiol-Yne photochemistry: case study with antibacterial polyaspartamide derivatives.

    PubMed

    Sardo, Carla; Nottelet, Benjamin; Triolo, Daniela; Giammona, Gaetano; Garric, Xavier; Lavigne, Jean-Philippe; Cavallaro, Gennara; Coudane, Jean

    2014-11-10

    In this work we wish to report on the covalent functionalization of polylactide (PLA) surfaces by photoradical thiol-yne to yield antibacterial surfaces. At first, hydrophilic and hydrophobic thiol fluorescent probes are synthesized and used to study and optimize the conditions of ligation on alkyne-PLA surfaces. In a second part, a new antibacterial polyaspartamide copolymer is covalently grafted. The covalent surface modification and the density of surface functionalization are evaluated by SEC and XPS analyses. No degradation of PLA chains is observed, whereas covalent grafting is confirmed by the presence of S2p and N1s signals. Antiadherence and antibiofilm activities are assessed against four bacterial strains, including Gram-negative and Gram-positive bacteria. A strong activity is observed with adherence reduction factors superior to 99.98% and biofilm formation decreased by 80%. Finally, in vitro cytocompatibility tests of the antibacterial surfaces are performed with L929 murine fibroblasts and show cell viability without promoting proliferation.

  13. Physical Activity and Albuminuria

    PubMed Central

    Robinson, Emily S.; Fisher, Naomi D.; Forman, John P.; Curhan, Gary C.

    2010-01-01

    Higher urinary albumin excretion predicts future cardiovascular disease, hypertension, and chronic kidney disease. Physical activity improves endothelial function so activity may reduce albuminuria. Among diabetics, physical activity decreases albuminuria. In nondiabetics, prior studies have shown no association. The authors explored the cross-sectional association between physical activity and albuminuria in 3,587 nondiabetic women in 2 US cohorts, the Nurses’ Health Study I in 2000 and the Nurses’ Health Study II in 1997. Physical activity was expressed as metabolic equivalents per week. The outcome was the top albumin/creatinine ratio (ACR) decile. Multivariate logistic regression was used. Secondary analyses explored the ACR association with strenuous activity and walking. The mean age was 58.6 years. Compared with women in the lowest physical activity quintile, those in the highest quintile had a multivariate-adjusted odds ratio for the top ACR decile of 0.65 (95% confidence interval (CI): 0.46, 0.93). The multivariate-adjusted odds ratio for the top ACR decile for those with greater than 210 minutes per week of strenuous activity compared with no strenuous activity was 0.61 (95% CI: 0.37, 0.99), and for those in the highest quintile of walking compared with the lowest quintile, it was 0.69 (95% CI: 0.47, 1.02). Greater physical activity is associated with a lower ACR in nondiabetic women. PMID:20133515

  14. Activated carbon from biomass

    NASA Astrophysics Data System (ADS)

    Manocha, S.; Manocha, L. M.; Joshi, Parth; Patel, Bhavesh; Dangi, Gaurav; Verma, Narendra

    2013-06-01

    Activated carbon are unique and versatile adsorbents having extended surface area, micro porous structure, universal adsorption effect, high adsorption capacity and high degree of surface reactivity. Activated carbons are synthesized from variety of materials. Most commonly used on a commercial scale are cellulosic based precursors such as peat, coal, lignite wood and coconut shell. Variation occurs in precursors in terms of structure and carbon content. Coir having very low bulk density and porous structure is found to be one of the valuable raw materials for the production of highly porous activated carbon and other important factor is its high carbon content. Exploration of good low cost and non conventional adsorbent may contribute to the sustainability of the environment and offer promising benefits for the commercial purpose in future. Carbonization of biomass was carried out in a horizontal muffle furnace. Both carbonization and activation were performed in inert nitrogen atmosphere in one step to enhance the surface area and to develop interconnecting porosity. The types of biomass as well as the activation conditions determine the properties and the yield of activated carbon. Activated carbon produced from biomass is cost effective as it is easily available as a waste biomass. Activated carbon produced by combination of chemical and physical activation has higher surface area of 2442 m2/gm compared to that produced by physical activation (1365 m2/gm).

  15. Physiologic activities of the contact activation system.

    PubMed

    Schmaier, Alvin H

    2014-05-01

    The plasma contact activation (CAS) and kallikrein/kinin (KKS) systems consist of 4 proteins: factor XII, prekallikrein, high molecular weight kininogen, and the bradykinin B2 receptor. Murine genetic deletion of factor XII (F12(-/-)), prekallikrein (Klkb1(-/-)), high molecular weight kininogen (Kgn1(-/-)) and the bradykinin B2 receptor (Bdkrb2(-/-)) yield animals protected from thrombosis. With possible exception of F12(-/-) and Kgn1(-/-) mice, the mechanism(s) for thrombosis protection is not reduced contact activation. Bdkrb2(-/-) mice are best characterized and they are protected from thrombosis through over expression of components of the renin angiotensin system (RAS) leading to elevated prostacyclin with vascular and platelet inhibition. Alternatively, prolylcarboxypeptidase, a PK activator and degrader of angiotensin II, when deficient in the mouse leads to a prothrombotic state. Its mechanism for increased thrombosis also is mediated in part by components of the RAS. These observations suggest that thrombosis in mice of the CAS and KKS are mediated in part through the RAS and independent of reduced contact activation. PMID:24759141

  16. Marine Biology Activities. Ocean Related Curriculum Activities.

    ERIC Educational Resources Information Center

    Pauls, John

    The ocean affects all of our lives. Therefore, awareness of and information about the interconnections between humans and oceans are prerequisites to making sound decisions for the future. Project ORCA (Ocean Related Curriculum Activities) has developed interdisciplinary curriculum materials designed to meet the needs of students and teachers…

  17. Improved Therapeutic Profiles of PLA2-Free Bee Venom Prepared by Ultrafiltration Method

    PubMed Central

    Lee, Hyunkyoung; Pyo, Min-Jung; Bae, Seong Kyeong; Heo, Yunwi; Kim, Choul Goo; Kang, Changkeun

    2015-01-01

    Bee venom (BV) has long been used in traditional Eastern and Western medicine for chronic inflammation, pain and skin therapy. Human exposure to BV, however, often causes unwanted adverse effects and is even fatal in some cases. Phospholipase A2 (PLA2) of BV is now suspected to play a key role in these adverse effects. We investigated the potential use of PLA2-free bee venom (PBV) as a replacement for BV in cosmetic products. PBV prepared by molecular weight cut-off ultrafiltration exhibits a superior profile in comparison with regular BV, by inhibiting elastase activity and suppressing the induction of nitric oxide (NO) and metalloproteinase-9 (MMP-9), while retaining the effects of cell proliferation and protection against ultraviolet B (UVB)-induced damage in human dermal fibroblast cells. PBV thus appears to be more promising than BV as a cosmetic ingredient with a reduced potential for adverse reactions in the recipient. PMID:25874031

  18. Inhibition of PAF synthesis by stimulated human polymorphonuclear leucocytes with cloricromene, an inhibitor of phospholipase A2 activation.

    PubMed Central

    Ribaldi, E.; Mezzasoma, A. M.; Francescangeli, E.; Prosdocimi, M.; Nenci, G. G.; Goracci, G.; Gresele, P.

    1996-01-01

    1. A phospholipase A2 (PLA2) represents the key enzyme in the remodelling pathway of platelet-activating factor (PAF) synthesis in human polymorphonuclear (PMN) leucocytes. 2. PLA2 activation is also the rate-limiting step for the release of the arachidonic acid utilized for the synthesis of leukotrienes in stimulated leucocytes; however, it is unknown whether the PLA2s involved in the two biosynthetic pathways are identical. 3. Cloricromene (8-monochloro-3-beta-diethylaminoethyl-4-methyl-7-ethoxy- carbonylmethoxy coumarin) is an antithrombotic coumarin derivative which inhibits platelet and leucocyte function and suppresses arachidonic acid liberation by interfering with PLA2 activation. 4. The aim of the present study was to assess whether chloricromene inhibits PAF synthesis by stimulated human polymorphonuclear leucocytes (PMNs). 5. Cloricromene (50-500 microM) inhibited in a concentration-dependent manner the release of PAF, as measured by h.p.l.c. bioassay, from A23187-stimulated PMNs. Significant inhibition (45%) of PAF-release was obtained with 50 microM cloricromene and the IC50 was 85 microM. Mepacrine (500 microM), a non-specific PLA2 inhibitor, strikingly reduced PAF release. 6. The incorporation of [3H]-acetate into [3H]-PAF induced by serum-treated zymosan in human PMNs was also inhibited concentration-dependently by cloricromene, with an IC50 of 105 microM. Mepacrine also suppressed [3H]-acetate incorporation into [3H]-PAF. 7. Cloricromene did not affect the activities of the enzymes involved in PAF-synthesis acetyltransferase or phosphocholine transferase. 8. Our data demonstrate that cloricromene, an inhibitor of PLA2-activation in human leucocytes, reduces the synthesis of PAF by stimulated PMNs. This finding has a twofold implication: the PLA2s (or the mechanisms that regulate their activation) involved in PAF synthesis and arachidonate release in human leucocytes are either identical or else indistinguishable by their sensitivity to cloricromene

  19. α-Synuclein-induced synapse damage in cultured neurons is mediated by cholesterol-sensitive activation of cytoplasmic phospholipase A2.

    PubMed

    Bate, Clive; Williams, Alun

    2015-01-01

    The accumulation of aggregated forms of the α-synuclein (αSN) is associated with the pathogenesis of Parkinson's disease (PD) and Dementia with Lewy Bodies. The loss of synapses is an important event in the pathogenesis of these diseases. Here we show that aggregated recombinant human αSN, but not βSN, triggered synapse damage in cultured neurons as measured by the loss of synaptic proteins. Pre-treatment with the selective cytoplasmic phospholipase A2 (cPLA2) inhibitors AACOCF3 and MAFP protected neurons against αSN-induced synapse damage. Synapse damage was associated with the αSN-induced activation of synaptic cPLA2 and the production of prostaglandin E2. The activation of cPLA2 is the first step in the generation of platelet-activating factor (PAF) and PAF receptor antagonists (ginkgolide B or Hexa-PAF) also protect neurons against αSN-induced synapse damage. αSN-induced synapse damage was also reduced in neurons pre-treated with the cholesterol synthesis inhibitor (squalestatin). These results are consistent with the hypothesis that αSN triggered synapse damage via hyperactivation of cPLA2. They also indicate that αSN-induced activation of cPLA2 is influenced by the cholesterol content of membranes. Inhibitors of this pathway that can cross the blood brain barrier may protect against the synapse damage seen during PD. PMID:25761116

  20. Lightning Activities and Earthquakes

    NASA Astrophysics Data System (ADS)

    Liu, Jann-Yenq

    2016-04-01

    The lightning activity is one of the key parameters to understand the atmospheric electric fields and/or currents near the Earth's surface as well as the lithosphere-atmosphere coupling during the earthquake preparation period. In this study, to see whether or not lightning activities are related to earthquakes, we statistically examine lightning activities 30 days before and after 78 land and 230 sea M>5.0 earthquakes in Taiwan during the 12-year period of 1993-2004. Lightning activities versus the location, depth, and magnitude of earthquakes are investigated. Results show that lightning activities tend to appear around the forthcoming epicenter and are significantly enhanced a few, especially 17-19, days before the M>6.0 shallow (depth D< 20 km) land earthquakes. Moreover, the size of the area around the epicenter with the statistical significance of lightning activity enhancement is proportional to the earthquake magnitude.

  1. Thermally Activated Driver

    NASA Technical Reports Server (NTRS)

    Kinard, William H.; Murray, Robert C.; Walsh, Robert F.

    1987-01-01

    Space-qualified, precise, large-force, thermally activated driver (TAD) developed for use in space on astro-physics experiment to measure abundance of rare actinide-group elements in cosmic rays. Actinide cosmic rays detected using thermally activated driver as heart of event-thermometer (ET) system. Thermal expansion and contraction of silicone oil activates driver. Potential applications in fluid-control systems where precise valve controls are needed.

  2. Activated recombinant adenovirus proteinases

    SciTech Connect

    Anderson, C.W.; Mangel, W.F.

    1999-08-10

    This application describes methods and expression constructs for producing activatable recombinant adenovirus proteinases. Purified activatable recombinant adenovirus proteinases and methods of purification are described. Activated adenovirus proteinases and methods for obtaining activated adenovirus proteinases are further included. Isolated peptide cofactors of adenovirus proteinase activity, methods of purifying and identifying peptide cofactors are also described. Antibodies immunoreactive with adenovirus proteinases, immunospecific antibodies, and methods for preparing them are also described. Other related methods and materials are also described. 29 figs.

  3. Activated recombinant adenovirus proteinases

    DOEpatents

    Anderson, Carl W.; Mangel, Walter F.

    1999-08-10

    This application describes methods and expression constructs for producing activatable recombinant adenovirus proteinases. Purified activatable recombinant adenovirus proteinases and methods of purification are described. Activated adenovirus proteinases and methods for obtaining activated adenovirus proteinases are further included. Isolated peptide cofactors of adenovirus proteinase activity, methods of purifying and identifying said peptide cofactors are also described. Antibodies immunoreactive with adenovirus proteinases, immunospecific antibodies, and methods for preparing them are also described. Other related methods and materials are also described.

  4. Active unilateral condylar hyperplasia.

    PubMed

    Luz, J G; de Rezende, J R; de Araújo, V C; Chilvarquer, I

    1994-01-01

    Two cases of active unilateral condylar hyperplasia which were treated with condylectomy alone are presented. The first case was an adult form and the other a juvenile form. Both were classified as active by using 99Tc bone scintigraphy. Clinical and radiographic features of both cases conformed to the hemimandibular hypertrophy type. Satisfactory facial symmetry and dental occlusion were achieved. Histopathological data confirmed the activity of the articular cartilage layers. PMID:8181091

  5. Activity in distant comets

    NASA Technical Reports Server (NTRS)

    Luu, Jane X.

    1992-01-01

    Activity in distant comets remains a mystery in the sense that we still have no complete theory to explain the various types of activity exhibited by different comets at large distances. This paper explores the factors that should play a role in determining activity in a distant comet, especially in the cases of comet P/Tempel 2, comet Schwassmann-Wachmann 1, and 2060 Chiron.

  6. Crew activities in space

    NASA Technical Reports Server (NTRS)

    Bluford, G. S., Jr.

    1981-01-01

    One of the mission requirements of the Space Shuttle is to serve as a working platform for experiments in space. Many of these experiments will be performed by crewmembers (mission specialists and payload specialists) in a general purpose laboratory called Spacelab. All nonexperiment-related activities or housekeeping activities will be done in the Orbiter, while most of the mission-related activities (experiments) will be done in Spacelab. In order for experimenters to design their experiments to best utilize the capabilities of the Orbiter, the Spacelab, and the crew, the working environment in the Orbiter and in Spacelab is described. In addition, the housekeeping activities required of the crew are summarized.

  7. Physical Activity and Cancer

    MedlinePlus

    ... of scientists, ranging from experts in basic biological science to those with expertise in community behavioral interventions to increase physical activity. This combination of scientists and expertise will ...

  8. NASA metrication activities

    NASA Technical Reports Server (NTRS)

    Vlannes, P. N.

    1978-01-01

    NASA's organization and policy for metrification, history from 1964, NASA participation in Federal agency activities, interaction with nongovernmental metrication organizations, and the proposed metrication assessment study are reviewed.

  9. Antimicrobial activity of allyl isothiocyanate used to coat biodegradable composite films as affected by storage and handling conditions

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We evaluated the effects of storage and handling conditions on the antimicrobial activity of biodegradable composite films (polylactic acid and sugar beet pulp) coated with allyl isothiocyanate (AIT). Polylactic acid (PLA) and chitosan were incorporated with AIT and coated on one side of the film. T...

  10. Active Flow Control Activities at NASA Langley

    NASA Technical Reports Server (NTRS)

    Anders, Scott G.; Sellers, William L., III; Washburn, Anthony E.

    2004-01-01

    NASA Langley continues to aggressively investigate the potential advantages of active flow control over more traditional aerodynamic techniques. This paper provides an update to a previous paper and describes both the progress in the various research areas and the significant changes in the NASA research programs. The goals of the topics presented are focused on advancing the state of knowledge and understanding of controllable fundamental mechanisms in fluids as well as to address engineering challenges. An organizational view of current research activities at NASA Langley in active flow control as supported by several projects is presented. On-center research as well as NASA Langley funded contracts and grants are discussed at a relatively high level. The products of this research are to be demonstrated either in bench-top experiments, wind-tunnel investigations, or in flight as part of the fundamental NASA R&D program and then transferred to more applied research programs within NASA, DOD, and U.S. industry.

  11. Activity Book: Ocean Ecology.

    ERIC Educational Resources Information Center

    Learning, 1992

    1992-01-01

    Presents a collection of activities to help elementary students study ocean ecology. The activities have students investigate ocean inhabitants, analyze animal adaptations, examine how temperature and saltiness affect ocean creatures, and learn about safeguarding the sea. Student pages offer reproducible learning sheets. (SM)

  12. [Field Learning Activities].

    ERIC Educational Resources Information Center

    Nolde Forest Environmental Education Center, Reading, PA.

    Seventy field activities, pertinent to outdoor, environmental studies, are described in this compilation. Designed for elementary and junior high school students, the activities cover many discipline areas--science, social studies, language arts, health, history, mathematics, and art--and many are multidisciplinary in use. Topics range from soil…

  13. Rainy Day Activities.

    ERIC Educational Resources Information Center

    Texas Child Care, 1997

    1997-01-01

    Experienced caregivers plan ahead for rainy days. This article describes specific rainy day activities for young children, such as books and crafts to learn about rain (rain in a jar, making a rainbow), simple cooking activities (taffy pull, cinnamon candy tea), and games (mummy wrap, hunt the thimble, rain lotto). (EV)

  14. Activities of the ILO.

    ERIC Educational Resources Information Center

    Labour Education, 1984

    1984-01-01

    Seven articles on International Labour Organization (ILO) activities cover study groups at ILO headquarters, a Philippine rural workers seminar, women's participation in Central American union activities, worksite courses in India, and seminars and symposia in Cape Verde, Mauritius, and Sierra Leone. (SK)

  15. Active Students in Webinars

    ERIC Educational Resources Information Center

    Kolås, Line; Nordseth, Hugo; Yri, Jørgen Sørlie

    2015-01-01

    To ensure student activity in webinars we have defined 10 learning tasks focusing on production and communication e.g. collaborative writing, discussion and polling, and investigated how the technology supports the learning activities. The three project partners in the VisPed-project use different video-conferencing systems, and we analyzed how it…

  16. The Activity of Trypsin

    ERIC Educational Resources Information Center

    Russo, Salvatore F.; Holzman, Tom

    1977-01-01

    Describes an experiment that illustrates the following points concerning the experimental determination of trypsin activity: (1) there is a difference in basing enzyme concentration on weight, absorbance, or active sites; and (2) the method of expressing enzyme concentration determines the value of specific, molecular, and catalytic center…

  17. Emotionally Intense Science Activities

    ERIC Educational Resources Information Center

    King, Donna; Ritchie, Stephen; Sandhu, Maryam; Henderson, Senka

    2015-01-01

    Science activities that evoke positive emotional responses make a difference to students' emotional experience of science. In this study, we explored 8th Grade students' discrete emotions expressed during science activities in a unit on Energy. Multiple data sources including classroom videos, interviews and emotion diaries completed at the end of…

  18. Games and Word Activities.

    ERIC Educational Resources Information Center

    Northwest Regional Educational Lab., Portland, OR.

    Games and word activities give children another way to integrate their learning and reinforce their literacy skills. They provide different and enjoyable contexts in which children can apply what they are learning. This booklet offers activities which provide a sampling of "fun" ways for tutors to support and supplement their tutees' classroom…

  19. Active Healthy Summer

    ERIC Educational Resources Information Center

    Elliott, Eloise

    2005-01-01

    Summer break is almost here for most elementary teachers and students. Warmer weather and additional free time to make choices create more opportunities to be physically active, whether home alone or out with friends and family. This article describes ways by which physical education specialists can encourage students' physical activity by…

  20. Coordinating Shared Activities

    NASA Technical Reports Server (NTRS)

    Clement, Bradley

    2004-01-01

    Shared Activity Coordination (ShAC) is a computer program for planning and scheduling the activities of an autonomous team of interacting spacecraft and exploratory robots. ShAC could also be adapted to such terrestrial uses as helping multiple factory managers work toward competing goals while sharing such common resources as floor space, raw materials, and transports. ShAC iteratively invokes the Continuous Activity Scheduling Planning Execution and Replanning (CASPER) program to replan and propagate changes to other planning programs in an effort to resolve conflicts. A domain-expert specifies which activities and parameters thereof are shared and reports the expected conditions and effects of these activities on the environment. By specifying these conditions and effects differently for each planning program, the domain-expert subprogram defines roles that each spacecraft plays in a coordinated activity. The domain-expert subprogram also specifies which planning program has scheduling control over each shared activity. ShAC enables sharing of information, consensus over the scheduling of collaborative activities, and distributed conflict resolution. As the other planning programs incorporate new goals and alter their schedules in the changing environment, ShAC continually coordinates to respond to unexpected events.

  1. Reflections on Activity Theory

    ERIC Educational Resources Information Center

    Bakhurst, David

    2009-01-01

    It is sometimes suggested that activity theory represents the most important legacy of Soviet philosophy and psychology. But what exactly "is" activity theory? The canonical account in the West is given by Engestrom, who identifies three stages in the theory's development: from Vygotsky's insights, through Leontiev's articulation of the…

  2. Obesity, Physical Activity - Children.

    ERIC Educational Resources Information Center

    Gilliam, Thomas B.

    Childhood obesity starts at a very early age, and preventive measures taken early enough may retard the development of fat cells. It appears that physical activity plays an important role in reducing obesity. The activity program must start early, in preschool days. It is felt that screening children for obesity when they first enter school and…

  3. Science World Activities Book.

    ERIC Educational Resources Information Center

    Wisconsin Academy of Sciences, Arts and Letters, Madison.

    This document consists of three sections. Section I contains 19 activities developed by master teachers for the Science World '84 summer science program. These activities focus on studies involving airplane controls, trash bag kites, computers, meteorology, compass orienteering, soils, aquatic ecosystems, bogs, and others. Objectives, materials…

  4. Peak Longevity Physical Activity

    Cancer.gov

    People who engage in three to five times the recommended minimum level of leisure-time physical activity derive the greatest benefit in terms of mortality reduction when compared with people who do not engage in leisure-time physical activity.

  5. ZOOMsci Activity Guide.

    ERIC Educational Resources Information Center

    Wade, Meredith

    This activity guide is based on the Public Broadcasting System's (PBS) program "ZOOM." It is designed for educators with activities that are categorized into three themes: (1) Things That Go, which includes "Air" which explores air pressure, "Rubber Bands" which discovers the potential energy of rubber bands, "Baking Soda and Vinegar" which…

  6. Active galactic nuclei

    PubMed Central

    Fabian, Andrew C.

    1999-01-01

    Active galactic nuclei are the most powerful, long-lived objects in the Universe. Recent data confirm the theoretical idea that the power source is accretion into a massive black hole. The common occurrence of obscuration and outflows probably means that the contribution of active galactic nuclei to the power density of the Universe has been generally underestimated. PMID:10220363

  7. Activation of fly ash

    DOEpatents

    Corbin, D.R.; Velenyi, L.J.; Pepera, M.A.; Dolhyj, S.R.

    1986-08-19

    Fly ash is activated by heating a screened magnetic fraction of the ash in a steam atmosphere and then reducing, oxidizing and again reducing the hydrothermally treated fraction. The activated fly ash can be used as a carbon monoxide disproportionating catalyst useful in the production of hydrogen and methane.

  8. Laboratory Activities in Israel

    ERIC Educational Resources Information Center

    Mamlok-Naaman, Rachel; Barnea, Nitza

    2012-01-01

    Laboratory activities have long had a distinctive and central role in the science curriculum, and science educators have suggested that many benefits accrue from engaging students in science laboratory activities. Many research studies have been conducted to investigate the educational effectiveness of laboratory work in science education in…

  9. Curriculum Activities on Aging.

    ERIC Educational Resources Information Center

    Schmall, Vicki L.; Benge, Nancy

    This paper contains learning activities on aging for use with elementary, high school, and university students in health, family relationships, social studies, and art courses. The activities are intended to help youth develop a more realistic understanding of the aging process and to become aware of both the problems and benefits associated with…

  10. Nutrition Activities Resource Guide.

    ERIC Educational Resources Information Center

    New York City Board of Education, Brooklyn, NY. Div. of Special Education.

    The resource guide suggests activities to help special education students make appropriate choices about their nutritional habits. It is explained that the activities can be infused into other curriculum areas. The guide consists of five themes and includes performance objectives for each: foods eaten at school (planning a school lunch, keeping a…

  11. Activation of fly ash

    DOEpatents

    Corbin, David R.; Velenyi, Louis J.; Pepera, Marc A.; Dolhyj, Serge R.

    1986-01-01

    Fly ash is activated by heating a screened magnetic fraction of the ash in a steam atmosphere and then reducing, oxidizing and again reducing the hydrothermally treated fraction. The activated fly ash can be used as a carbon monoxide disproportionating catalyst useful in the production of hydrogen and methane.

  12. Learning Activities for Toddlers.

    ERIC Educational Resources Information Center

    Texas Child Care, 1996

    1996-01-01

    Suggests activities to help toddlers develop skills in the four important areas of self-help, creativity, world mastery, and coordination. Activities include hand washing, button practice, painting, movement and music, bubble making, creation of a nature mural, and a shoe print trail. (TJQ)

  13. Active and Healthy Schools

    ERIC Educational Resources Information Center

    Ball, Stephen; Kovarik, Jessica; Leidy, Heather

    2015-01-01

    The Active and Healthy School Program (AHS) can be used to alter the culture and environment of a school to help children make healthier choices. The purpose of this study was to determine the effectiveness of AHS to increase physical activity while decreasing total screen time, increase healthy food choices, and improve knowledge about physical…

  14. Calculator-Active Materials.

    ERIC Educational Resources Information Center

    Crow, Tracy, Ed.; Harris, Julia, Ed.

    1997-01-01

    This journal contains brief descriptions of calculator-active materials that were found using Resource Finder, the searchable online catalog of curriculum resources from the Eisenhower National Clearinghouse (ENC). It features both the calculators themselves and the activity books that are used with them. Among the calculators included are those…

  15. Activating Event Knowledge

    ERIC Educational Resources Information Center

    Hare, Mary; Jones, Michael; Thomson, Caroline; Kelly, Sarah; McRae, Ken

    2009-01-01

    An increasing number of results in sentence and discourse processing demonstrate that comprehension relies on rich pragmatic knowledge about real-world events, and that incoming words incrementally activate such knowledge. If so, then even outside of any larger context, nouns should activate knowledge of the generalized events that they denote or…

  16. Bonus Activity Book. Peacemakers.

    ERIC Educational Resources Information Center

    Whitman, Betsy Blizard

    1992-01-01

    Activity book helps elementary students learn about peace and see themselves as peacemakers and peacekeepers. Students are introduced to literary and historical figures who have worked for peace and won the Nobel Peace Prize. Activities teach students that peace means more than calm situations or absence of war. (SM)

  17. Vegetable Soup Activities.

    ERIC Educational Resources Information Center

    Shepard, Mary; Shepard, Ray

    Vegetable Soup is a new children's television series whose purpose is to counter the negative and destructive effects of racial isolation. This manual gives detailed instructions for discussion of activities that are presented during the television series such as: crafts, games, recipes, language activities, and children's questions. A list of…

  18. Student Activities. Managing Liability.

    ERIC Educational Resources Information Center

    Bennett, Barbara; And Others

    This monograph suggests ways that college or university administrations can undertake a systematic and careful review of the risks posed by students' activities. Its purpose is to provide guidance in integrating the risk management process into a school's existing approaches to managing student organizations and activities. It is noted that no…

  19. Untangling occupation and activity.

    PubMed

    Pierce, D

    2001-01-01

    Activity and occupation are two core concepts of occupational therapy that are in need of differentiation. Occupation is defined here as a person's personally constructed, one-time experience within a unique context. Activity is defined as a more general, culturally shared idea about a category of action. The ways in which subjectivity and context are handled within the concepts of occupation and activity are keys to disentangling them. The proposed untangling of the two concepts into distinct definitions is congruent with their historical origins as well as with current definitional trends. Once occupation and activity are recognized as two separate and equally valuable concepts, they offer a rich set of theoretical relations for exploration. The clarity that will result from differentiating occupation and activity will enhance disciplinary discourse and research as well as enhance the intervention efficacy, moral surety, and political strength of the profession.

  20. Active element pattern

    NASA Astrophysics Data System (ADS)

    Pozar, D. M.

    1994-08-01

    This review article will discuss the use of the active element pattern for prediction of the scan performance of large phased array antennas. The introduction and application of the concept of the active element pattern goes back at least 30 years (1) -(6) , but the subject is generally not covered in modern antenna engineering textbooks or handbooks, and many contemporary workers are unfamiliar with this simple but powerful idea. In addition, early references on this subject do not provide a rigorous discussion or derivation of the active element pattern, relying instead on a more qualitative interpretation. The purpose of this communication is to make the technique of active element patterns more accessible to antenna engineers, and to provide a new derivation of the basic active element pattern relations in terms of scattering parameters.

  1. Endothelial PKCα-MAPK/ERK-phospholipase A2 pathway activation as a response of glioma in a triple culture model. A new role for pericytes?

    PubMed

    Anfuso, Carmelina Daniela; Motta, Carla; Giurdanella, Giovanni; Arena, Valeria; Alberghina, Mario; Lupo, Gabriella

    2014-04-01

    In view of understanding the molecular mechanisms through which angiogenic switch on happens in the early phases of reciprocal interaction between tumor and cells constituting microvessel, a triple culture model in which endothelial cells (EC), pericytes (PC) and glioma C6 cells were cultured together. In the present work, we observed that C6 enhanced EC proliferation. This effect was reduced by cytosolic and Ca(2+)-independent phospholipase A2 (cPLA2 and iPLA2), cyclooxygenase-2 (COX-2), PI3-K, MEK-1, and ERK1/2 inhibitors and by siRNAs against both PLA2s. In EC, C6 induced an increase in iPLA2, cPLA2 and COX-2 total protein expression. Moreover, the increase in endothelial cPLA2 phosphorylation was attenuated by kinase inhibitors. Both EC proliferation and signal protein phosphorylation were attenuated when PC were in triple culture. In EC/C6 supernatants, and, in a lesser extent, in EC/PC co-cultures, an enhancement in prostaglandins E2 (PGE2) was found. The presence of PC in triple-cultures caused a decrease in production of PGE2 respect to EC/C6 double-cultures. In all systems, AACOCF3 and BEL significantly reduced PGE2 secretion. In Matrigel-based assays, emerging branch points from EC cell bodies and tubule-like structures were observed. C6 conditioned EC/PC co-cultures in constituting poorly organized tubules. Transfection of EC with c- and iPLA2 siRNA strongly reduced in vitro tubulogenesis. Data here reported indicate that PKCα, ERK kinase phosphorylation, PLA2s and COX-2 activation, and PGE2 production in EC stimulated by tumor cells are coincident phenomena and could represent therapeutic targets in chemoprevention of glioma. Moreover, PC exhibited an important "modulating" role in the initial stages of angiogenesis driven by a brain tumor.

  2. Active optical zoom system

    DOEpatents

    Wick, David V.

    2005-12-20

    An active optical zoom system changes the magnification (or effective focal length) of an optical imaging system by utilizing two or more active optics in a conventional optical system. The system can create relatively large changes in system magnification with very small changes in the focal lengths of individual active elements by leveraging the optical power of the conventional optical elements (e.g., passive lenses and mirrors) surrounding the active optics. The active optics serve primarily as variable focal-length lenses or mirrors, although adding other aberrations enables increased utility. The active optics can either be LC SLMs, used in a transmissive optical zoom system, or DMs, used in a reflective optical zoom system. By appropriately designing the optical system, the variable focal-length lenses or mirrors can provide the flexibility necessary to change the overall system focal length (i.e., effective focal length), and therefore magnification, that is normally accomplished with mechanical motion in conventional zoom lenses. The active optics can provide additional flexibility by allowing magnification to occur anywhere within the FOV of the system, not just on-axis as in a conventional system.

  3. Emotionally Intense Science Activities

    NASA Astrophysics Data System (ADS)

    King, Donna; Ritchie, Stephen; Sandhu, Maryam; Henderson, Senka

    2015-08-01

    Science activities that evoke positive emotional responses make a difference to students' emotional experience of science. In this study, we explored 8th Grade students' discrete emotions expressed during science activities in a unit on Energy. Multiple data sources including classroom videos, interviews and emotion diaries completed at the end of each lesson were analysed to identify individual student's emotions. Results from two representative students are presented as case studies. Using a theoretical perspective drawn from theories of emotions founded in sociology, two assertions emerged. First, during the demonstration activity, students experienced the emotions of wonder and surprise; second, during a laboratory activity, students experienced the intense positive emotions of happiness/joy. Characteristics of these activities that contributed to students' positive experiences are highlighted. The study found that choosing activities that evoked strong positive emotional experiences, focused students' attention on the phenomenon they were learning, and the activities were recalled positively. Furthermore, such positive experiences may contribute to students' interest and engagement in science and longer term memorability. Finally, implications for science teachers and pre-service teacher education are suggested.

  4. Active touch sensing

    PubMed Central

    Prescott, Tony J.; Diamond, Mathew E.; Wing, Alan M.

    2011-01-01

    Active sensing systems are purposive and information-seeking sensory systems. Active sensing usually entails sensor movement, but more fundamentally, it involves control of the sensor apparatus, in whatever manner best suits the task, so as to maximize information gain. In animals, active sensing is perhaps most evident in the modality of touch. In this theme issue, we look at active touch across a broad range of species from insects, terrestrial and marine mammals, through to humans. In addition to analysing natural touch, we also consider how engineering is beginning to exploit physical analogues of these biological systems so as to endow robots with rich tactile sensing capabilities. The different contributions show not only the varieties of active touch—antennae, whiskers and fingertips—but also their commonalities. They explore how active touch sensing has evolved in different animal lineages, how it serves to provide rapid and reliable cues for controlling ongoing behaviour, and even how it can disintegrate when our brains begin to fail. They demonstrate that research on active touch offers a means both to understand this essential and primary sensory modality, and to investigate how animals, including man, combine movement with sensing so as to make sense of, and act effectively in, the world. PMID:21969680

  5. Asp-49 is not an absolute prerequisite for the enzymic activity of low-M(r) phospholipases A2: purification, characterization and computer modelling of an enzymically active Ser-49 phospholipase A2, ecarpholin S, from the venom of Echis carinatus sochureki (saw-scaled viper).

    PubMed

    Polgár, J; Magnenat, E M; Peitsch, M C; Wells, T N; Clemetson, K J

    1996-11-01

    Several studies have shown that Asp-49 is the residue that controls calcium binding in, and so plays a critical role in the calcium-mediated activation of, low-M(r) group I-III phospholipases A2 (PLA2s). The present paper provides experimental evidence that Asp-49 is not an absolute prerequisite for the enzymic activity of PLA2s, and that proteins with amino acid(s) other than Asp at position 49 can exhibit significant phospholipase activity. The purification, complete amino acid sequence and characterization of ecarpholin S, a PLA2 from Echis carinatus sochureki (saw-scaled viper) venom, is described. This single-chain, 122-amino-acid, basic (pI 7.9) protein is a group II PLA2. Although Asp-49 is replaced by Ser and Tyr-28 by Phe (both of these positions being involved in the Ca(2+)-binding site of PLA2s), the lipolysis of soybean phosphatidylcholine and egg yolk in the presence of 10 mM CaCl2 was 1.5 times and 2.9 times greater respectively with ecarpholin S than with recombinant human group II PLA2. The Ca(2+)-dependencies of the enzymic activities of ecarpholin S and rPLA2 were found to be similar. Ecarpholin S added to washed platelets induced aggregation; the presence of Ca2+ was a prerequisite for this platelet-aggregating effect. Computer modelling of the Ca(2+)-binding site of Ser-49 PLA2 compared with the Asp-49 and Lys-49 forms, for which crystallographic data exist, shows that the Ca(2+)-binding site is sterically blocked by Lys-49 but not by Ser-49; in the latter, the Ser hydroxy group may replace the Asp carboxylate in stabilization of Ca2+ binding. Sequence comparisons of ecarpholin S and other low-M(r) PLA2s predicts the presence of a Ser-49 group in the protein family of low-M(r) PLA2s that is distinct from the Asp-49 and Lys-49 groups. PMID:8921006

  6. Biological activity of purpurogallin.

    PubMed

    Inamori, Y; Muro, C; Sajima, E; Katagiri, M; Okamoto, Y; Tanaka, H; Sakagami, Y; Tsujibo, H

    1997-05-01

    Purpurogallin showed antibacterial activity toward gram-positive bacteria. Strong activity against methicillin-resistant Staphylococcus aureus [minimal inhibitory concentration (MIC) against methicillin of 1600 micrograms/ml] was found, with MIC of 11.0 micrograms/ml. Purpurogallin inhibited the growth of all tested plants and decreased the chlorophyll content in the cotyledons of Brassica campestris subsp. rapa. It showed potent inhibitory activity against prolyl endopeptidase (the 50% inhibitory concentration was 1.6 x 10(-5) M), unlike its analogues, hinokitiol and tropolone.

  7. PLA recycling by hydrolysis at high temperature

    NASA Astrophysics Data System (ADS)

    Cristina, Annesini Maria; Rosaria, Augelletti; Sara, Frattari; Fausto, Gironi

    2016-05-01

    In this work the process of PLA hydrolysis at high temperature was studied, in order to evaluate the possibility of chemical recycling of this polymer bio-based. In particular, the possibility to obtain the monomer of lactic acid from PLA degradation was investigated. The results of some preliminary tests, performed in a laboratory batch reactor at high temperature, are presented: the experimental results show that the complete degradation of PLA can be obtained in relatively low reaction times.

  8. Evaluation of Phototoxic and Skin Sensitization Potentials of PLA2-Free Bee Venom

    PubMed Central

    Heo, Yunwi; Pyo, Min-Jung; Bae, Seong Kyeong; Lee, Hyunkyoung; Kwon, Young Chul; Kim, Je Hein; Kim, Bokyung; Kim, Choul Goo; Kang, Changkeun; Kim, Euikyung

    2015-01-01

    Bee venom (BV) from honey bee (Apis mellifera L.) has been used in oriental medicine and cosmetic ingredients because of its diverse pharmacological activities. In many studies, among BV components, phospholipase A2 (PLA2) is known as a major player in BV-induced allergic reaction. Therefore, we removed PLA2 from BV using ultrafiltration and then investigated in vitro phototoxicity and in vivo skin sensitization of PLA2-free BV (PBV) in comparison with regular BV. The 3T3 neutral red uptake phototoxicity assay can be appropriated to identify the phototoxic effect of a test substance upon the exposure of ultraviolet A. Chlorpromazine, a positive control, showed high levels of photoirritation factor and mean photo effect values, while BV and PBV had less of these values. Local lymph node assay is an alternative method to evaluate skin sensitization potential of chemicals. BALB/c mice were treated with p-phenylenediamine (PPD, positive control), BV, or PBV. In all of PPD concentrations, stimulation indexes (SI) as sensitizing potential of chemicals were ≥1.6, determined to be sensitizer, while SI levels of BV and PBV were below 1.6. Thus, based on these findings, we propose that both BV and PBV are nonphototoxic compounds and nonsensitizers. PMID:26347784

  9. Polybiguanide (PHMB) loaded in PLA scaffolds displaying high hydrophobic, biocompatibility and antibacterial properties.

    PubMed

    Llorens, Elena; Calderón, Silvia; del Valle, Luis J; Puiggalí, Jordi

    2015-05-01

    Polyhexamethylenebiguanide hydrochloride (PHMB), a low molecular weight polymer related to chlorohexidine (CHX), is a well-known antibacterial agent. In this study, polylactide (PLA) nanofibers loaded with PHMB were produced by electrospinning to obtain 3D biodegradable scaffolds with antibacterial properties. PLA fibers loaded with CHX were used as control. The electrospun fibers were studied and analyzed by SEM, FTIR, DSC and contact angle measurements. PHMB and CHX release from loaded scaffolds was evaluated, as well as their antibacterial activity and biocompatibility. The results showed that the nanofibers became smoother and their diameter smaller with increasing the amount of loaded PHMB. This feature led to an increase of both surface roughness and hydrophobicity of the scaffold. PHMB release was highly dependent on the hydrophilicity of the medium and differed from that determined for CHX. Lastly, PHMB-loaded PLA scaffolds showed antibacterial properties since they inhibited adhesion and bacterial growth, and exhibited biocompatible characteristics for the adhesion and proliferation of both fibroblast and epithelial cell lines. PMID:25746248

  10. Aqueous-core PEG-coated PLA nanocapsules for an efficient entrapment of water soluble anticancer drugs and a smart therapeutic response.

    PubMed

    Cosco, Donato; Paolino, Donatella; De Angelis, Francesco; Cilurzo, Felisa; Celia, Christian; Di Marzio, Luisa; Russo, Diego; Tsapis, Nicolas; Fattal, Elias; Fresta, Massimo

    2015-01-01

    Novel PEGylated PLA nanocapsules (PEG-AcPLA nanocapsules), loading high percentage of water soluble drugs have been formulated by using multiple emulsion technique without using conventional stabilizers. In particular, sodium deoxycholate hydrate has been used to obtain nanocapsules having a mean diameter of about 200 nm and a polydispersity index of ∼ 0.1. Gemcitabine hydrochloride (GEM) was used as a model of hydrophilic drug. GEM-loaded PEG-AcPLA nanocapsules demonstrated a high encapsulation efficacy and the drug-release followed a zero-order kinetic. MTT-assay evidenced an increased antitumor effect of GEM-loaded PEG-AcPLA nanocapsules compared to the free drug on different cancer cell lines and confocal laser scanning microscopy showed a significant improvement of cell interaction at 6h of incubation. In vivo anticancer activity of GEM-loaded PEG-AcPLA nanocapsules using two xenograft murine models of human solid tumors further supported the efficacy of this nano-drug, thus providing preliminary results about the potential clinical application of this innovative nanotherapeutic. PMID:25460850

  11. Algorithm-development activities

    NASA Technical Reports Server (NTRS)

    Carder, Kendall L.

    1994-01-01

    The task of algorithm-development activities at USF continues. The algorithm for determining chlorophyll alpha concentration, (Chl alpha) and gelbstoff absorption coefficient for SeaWiFS and MODIS-N radiance data is our current priority.

  12. Microglial Activation & Chronic Neurodegeneration

    PubMed Central

    Lull, Melinda E.; Block, Michelle L.

    2010-01-01

    Microglia, the resident innate immune cells in the brain, have long been implicated in the pathology of neurodegenerative diseases. Accumulating evidence points to activated microglia as a chronic source of multiple neurotoxic factors, including TNFα, NO, IL1-β, and reactive oxygen species (ROS), driving progressive neuron damage. Microglia can become chronically activated by either a single stimulus (ex. LPS or neuron damage) or multiple stimuli exposures to result in cumulative neuronal loss over time. While the mechanisms driving these phenomena are just beginning to be understood, reactive microgliosis (the microglial response to neuron damage) and ROS have been implicated as key mechanisms of chronic and neurotoxic microglial activation, particularly in the case of Parkinson’s Disease. Here, we review the mechanisms of neurotoxicity associated with chronic microglial activation and discuss the role of neuronal death and microglial ROS driving the chronic and toxic microglial phenotype. PMID:20880500

  13. Active noise reduction

    NASA Astrophysics Data System (ADS)

    Carter, J.

    1984-01-01

    Active Noise Reduction (ANR) techniques, singly and in combination with passive hearing protectors, offer the potential for increased sound protection, enhanced voice communications and improved wearability features for personnel exposed to unacceptable noise conditions. An enhanced closed loop active noise reduction system was miniaturized and incorporated into a standard Air Force flight helmet (HGU-26/P). This report describes the theory of design and operation, prototype configuration and operation, and electroacoustic performance and specifications for the ANR system. This system is theoretically capable of producing in excess of 30 decibels of active noise reduction. Electroacoustic measurements on a flat plate coupler demonstrated approximately 20 decibels of active noise reduction with the prototype unit. A performance evaluation of the integrated ANR unit will be conducted under laboratory and field conditions by government personnel to determine the feasibility of the system for use in military applications.

  14. Activities in Teaching Weather

    ERIC Educational Resources Information Center

    Tonn, Martin

    1977-01-01

    Presented is a unit composed of activities for teaching weather. Topics include cloud types and formation, simple weather instruments, and the weather station. Illustrations include a weather chart and instruments. A bibliography is given. (MA)

  15. Island Watershed Activity.

    ERIC Educational Resources Information Center

    Benson, Rod

    2003-01-01

    Describes a 90-minute "Island Watershed" activity to help earth science students understand the concept of the water cycle. Introduces a surface waters unit appropriate for students in grades 7-10. Includes watershed project guidelines. (Author/KHR)

  16. Authentic Listening Activities.

    ERIC Educational Resources Information Center

    Porter, Don; Roberts, Jon

    1981-01-01

    Discusses use of authentic listening experiences in second language classroom so that students will become involved in listening process demanded in authentic listening situations. Gives examples of sample classroom activities. (BK)

  17. French space activities

    NASA Technical Reports Server (NTRS)

    Blanc, R.

    1982-01-01

    The four main points of research and development of space programs by France are explained. The National Center of Space Studies is discussed, listing the missions of the Center and describing the activities of the staff.

  18. Creating Art Appreciation Activities.

    ERIC Educational Resources Information Center

    Heidt, Ann H.

    1986-01-01

    The experiences of college students enrolled as majors in elementary education in designing art appreciation activities for use in elementary classrooms are described. The college students had no art background. (RM)

  19. Active terahertz metamaterials

    SciTech Connect

    Chen, Hou-tong

    2009-01-01

    We demonstrate planar terahertz metamaterial devices enabling actively controllable transmission amplitude, phase, or frequency at room temperature via carrier depletion or photoexcitation in the semiconductor substrate or in semiconductor materials incorporated into the metamaterial structure.

  20. Planning activities in space

    NASA Technical Reports Server (NTRS)

    Chang, Kai-Hsiung

    1987-01-01

    Three aspects of planning activities in space are presented. These include generating plans efficiently, coordinating actions among multiple agents, and recovering from plan execution errors. Each aspect is discussed separately.

  1. A Big Gulp Activity.

    ERIC Educational Resources Information Center

    Kelly, Bruce

    1997-01-01

    Explains how to implement an activity in which students measure the volume of their oral cavities. Enables students to develop skills in estimation, measurement, connections, statistics, applying concepts and procedures, and communication. (DDR)

  2. PRESSURE ACTIVATED SEALANT TECHNOLOGY

    SciTech Connect

    Michael A. Romano

    2004-04-01

    The objective of this project is to develop new, efficient, cost effective methods of internally sealing natural gas pipeline leaks through the application of differential pressure activated sealants. In researching the current state of the art for gas pipeline sealing technologies we concluded that if the project was successful, it appeared that pressure activated sealant technology would provide a cost effective alternative to existing pipeline repair technology. From our analysis of current field data for a 13 year period from 1985 to 1997 we were able to identify 205 leaks that were candidates for pressure activated sealant technology, affirming that pressure activated sealant technology is a viable option to traditional external leak repairs. The data collected included types of defects, areas of defects, pipe sizes and materials, incident and operating pressures, ability of pipeline to be pigged and corrosion states. This data, and subsequent analysis, was utilized as a basis for constructing applicable sealant test modeling.

  3. Molecular docking studies and anti-enzymatic activities of Thai mango seed kernel extract against snake venoms.

    PubMed

    Leanpolchareanchai, Jiraporn; Pithayanukul, Pimolpan; Bavovada, Rapepol; Saparpakorn, Patchreenart

    2009-03-31

    The ethanolic extract from seed kernels of Thai mango (MSKE) (Mangifera indica L. cv. 'Fahlun') (Anacardiaceae) and its major phenolic principle (pentagalloyl glucopyranose) exhibited dose-dependent inhibitory effects on enzymatic activities of phospholipase A(2) (PLA(2)), hyaluronidase and L-amino acid oxidase (LAAO) of Calloselasma rhodostoma (CR) and Naja naja kaouthia (NK)venoms by in vitro tests. The anti-hemorrhagic and anti-dermonecrotic activities of MSKE against both venoms were clearly supported by in vivo tests. Molecular docking studies indicated that the phenolic molecules of the MSKE could selectively bind to the active sites or their proximity, or modify conserved residues that are critical for the catalysis of PLA(2), and selectively bind to the LAAO binding pocket of both CR and NK venoms and thereby inhibit their enzymatic activities. The results imply a potential use of MSKE against snake venoms.

  4. Intercreativity: Mapping Online Activism

    NASA Astrophysics Data System (ADS)

    Meikle, Graham

    How do activists use the Internet? This article maps a wide range of activist practice and research by applying and developing Tim Berners-Lee's concept of ‘intercreativity' (1999). It identifies four dimensions of Net activism: intercreative texts, tactics, strategies and networks. It develops these through examples of manifestations of Net activism around one cluster of issues: support campaigns for refugees and asylum seekers.

  5. RMS active damping augmentation

    NASA Technical Reports Server (NTRS)

    Gilbert, Michael G.; Scott, Michael A.; Demeo, Martha E.

    1992-01-01

    The topics are presented in viewgraph form and include: RMS active damping augmentation; potential space station assembly benefits to CSI; LaRC/JSC bridge program; control law design process; draper RMS simulator; MIMO acceleration control laws improve damping; potential load reduction benefit; DRS modified to model distributed accelerations; accelerometer location; Space Shuttle aft cockpit simulator; simulated shuttle video displays; SES test goals and objectives; and SES modifications to support RMS active damping augmentation.

  6. Information Activities in Australia

    NASA Astrophysics Data System (ADS)

    Hanada, Takeyoshi

    The last few years have seen an explosive growth in database and computer networking activities in Australia. At present there are six major information networks in Australia, which carry more than 400 locally produced databases and many others from overseas. AUSINET databases are exemplified. MIDAS (Multi-mode International Data Aquisition System) provides lower cost access to overseas databases than before. The paper also gives brief outline of various bodies which relate to information and library policy in Australia and regional cooperative activities.

  7. RAVEN Quality Assurance Activities

    SciTech Connect

    Cogliati, Joshua Joseph

    2015-09-01

    This report discusses the quality assurance activities needed to raise the Quality Level of Risk Analysis in a Virtual Environment (RAVEN) from Quality Level 3 to Quality Level 2. This report also describes the general RAVEN quality assurance activities. For improving the quality, reviews of code changes have been instituted, more parts of testing have been automated, and improved packaging has been created. For upgrading the quality level, requirements have been created and the workflow has been improved.

  8. Low activation ferritic alloys

    DOEpatents

    Gelles, David S.; Ghoniem, Nasr M.; Powell, Roger W.

    1986-01-01

    Low activation ferritic alloys, specifically bainitic and martensitic stainless steels, are described for use in the production of structural components for nuclear fusion reactors. They are designed specifically to achieve low activation characteristics suitable for efficient waste disposal. The alloys essentially exclude molybdenum, nickel, nitrogen and niobium. Strength is achieved by substituting vanadium, tungsten, and/or tantalum in place of the usual molybdenum content in such alloys.

  9. Low activation ferritic alloys

    DOEpatents

    Gelles, D.S.; Ghoniem, N.M.; Powell, R.W.

    1985-02-07

    Low activation ferritic alloys, specifically bainitic and martensitic stainless steels, are described for use in the production of structural components for nuclear fusion reactors. They are designed specifically to achieve low activation characteristics suitable for efficient waste disposal. The alloys essentially exclude molybdenum, nickel, nitrogen and niobium. Strength is achieved by substituting vanadium, tungsten, and/or tantalum in place of the usual molybdenum content in such alloys.

  10. Tinnitus activities treatment.

    PubMed

    Tyler, Richard S; Gogel, Stephanie A; Gehringer, Anne K

    2007-01-01

    Tinnitus Activities Treatment includes counseling of the whole person, and considers individual differences and needs. We consider four areas: thoughts and emotions, hearing and communication, sleep, and concentration. We typically use Partial Masking Sound Therapy, with a noise or music set to the lowest level that provides relief. A picture-based approach facilitates engagement of the patient, and provides thorough and structured counseling. We engage the patient by including homework and activities to demonstrate understanding and facilitate progress. PMID:17956807

  11. Synthesis and activity of 2-oxoamides containing long chain beta-amino acids.

    PubMed

    Constantinou-Kokotou, Violetta; Peristeraki, Anna; Kokotos, Christoforos G; Six, David A; Dennis, Edward A

    2005-07-01

    2-Oxoamides based on long chain beta-amino acids were synthesized. 1-Benzyl substituted long chain amines, needed for such synthesis, were synthesized starting from Boc-phenylalaninol. The oxidative conversion of a phenyl group to a carboxyl group was used as the key transformation synthetic step. The compounds synthesized were studied for their activity against GIVA PLA(2), and were proven to be weak inhibitors. PMID:15635664

  12. Phytase activity in lichens.

    PubMed

    Higgins, Niall F; Crittenden, Peter D

    2015-10-01

    Phytase activity was investigated in 13 lichen species using a novel assay method. The work tested the hypothesis that phytase is a component of the suite of surface-bound lichen enzymes that hydrolyse simple organic forms of phosphorus (P) and nitrogen (N) deposited onto the thallus surface. Hydrolysis of inositol hexaphosphate (InsP6 , the substrate for phytase) and appearance of lower-order inositol phosphates (InsP5 -InsP1 ), the hydrolysis products, were measured by ion chromatography. Phytase activity in Evernia prunastri was compared among locations with contrasting rates of N deposition. Phytase activity was readily measurable in epiphytic lichens (e.g. 11.3 μmol InsP6 hydrolysed g(-1)  h(-1) in Bryoria fuscescens) but low in two terricolous species tested (Cladonia portentosa and Peltigera membranacea). Phytase and phosphomonoesterase activities were positively correlated amongst species. In E. prunastri both enzyme activities were promoted by N enrichment and phytase activity was readily released into thallus washings. InsP6 was not detected in tree canopy throughfall but was present in pollen leachate. Capacity to hydrolyse InsP6 appears widespread amongst lichens potentially promoting P capture from atmospheric deposits and plant leachates, and P cycling in forest canopies. The enzyme assay used here might find wider application in studies on plant root-fungal-soil systems.

  13. Physical activity and obesity.

    PubMed

    Tremblay, A

    1999-04-01

    The regular practice of physical activity promotes metabolic adaptations that facilitate the regulation of energy and fat balance. These effects are important for a better control of body weight in the obese individual and should enable him or her to involve adipose tissue to a lesser extent in this regulation. Physical activity favours a negative energy and fat balance, particularly if activities are prolonged and vigorous. The achievement of a negative energy and fat balance with physical activity also strongly depends on the nutritional context in which it is performed. In the long term, an active lifestyle and low-fat food habits are expected to induce a substantial body weight loss in the obese. This weight loss is progressively attenuated over time, presumably because of the decreased impact of a reduced adipose tissue mass on the regulation of energy and fat balance. For the obese individual complying with an activity programme and healthy food habits, a body weight loss of 10% is a realistic goal before the occurrence of resistance to further loss of body fat.

  14. ABB: active bandwidth broker

    NASA Astrophysics Data System (ADS)

    Wong, Kason; Law, Eddie

    2001-07-01

    In this paper, we shall discuss a novel design on the policy-based management for the Internet. This design deploys the concept of active networking. As opposed to the traditional network design, active network empowers network node with the ability to manipulate data and program code in packets, and configure the network properties according to the needs of different applications. The policy-based management can control network routers in order to realize end-to-end Quality of Service (QoS), such as differentiated and integrated services, across the Internet. For the moment, the Internet Engineering Task Force (IETF) has defined the framework of the policy-based management. It employs a simple client/server model that uses Common Open Policy Service (COPS) protocol to facilitate policy management and control. Our design of Active Bandwidth Broker (ABB) belongs to an active application. Our goals are to distribute centralized workload of the policy-based management over multiple active nodes in the active networks, introduce mobility of the bandwidth brokers, and allows load sharing to the policy-based management. This results a network-wide intelligent, highly available, and consistent QoS control that allows performance protection for voice, video and Internet business application while reducing costs for growing networks.

  15. Biological and enzymatic activities of Micrurus sp. (Coral) snake venoms.

    PubMed

    Cecchini, Alessandra L; Marcussi, Silvana; Silveira, Lucas B; Borja-Oliveira, Caroline R; Rodrigues-Simioni, Léa; Amara, Susan; Stábeli, Rodrigo G; Giglio, José R; Arantes, Eliane C; Soares, Andreimar M

    2005-01-01

    The venoms of Micrurus lemniscatus carvalhoi, Micrurus frontalis frontalis, Micrurus surinamensis surinamensis and Micrurus nigrocinctus nigrocinctus were assayed for biological activities. Although showing similar liposome disrupting and myotoxic activities, M. frontalis frontalis and M. nigrocinctus nigrocinctus displayed higher anticoagulant and phospholipase A2 (PLA2) activities. The latter induced a higher edema response within 30 min. Both venoms were the most toxic as well. In the isolated chick biventer cervicis preparation, M. lemniscatus carvalhoi venom blocked the indirectly elicited twitch-tension response (85+/-0.6% inhibition after a 15 min incubation at 5 microg of venom/mL) and the response to acetylcholine (ACh; 55 or 110 microM), without affecting the response to KCl (13.4 mM). In mouse phrenic nerve-diaphragm preparation, the venom (5 microg/mL) produced a complete inhibition of the indirectly elicited contractile response after 50 min incubation and did not affect the contractions elicited by direct stimulation. M. lemniscatus carvalhoi inhibited 3H-L-glutamate uptake in brain synaptosomes in a Ca2+-, but not time, dependent manner. The replacement of Ca2+ by Sr2+ and ethylene glycol-bis(beta-aminoethyl ether) (EGTA), or alkylation of the venom with p-bromophenacyl bromide (BPB), inhibited 3H-L-glutamate uptake. M. lemniscatus carvalhoi venom cross-reacted with postsynaptic alpha-neurotoxins short-chain (antineurotoxin-II) and long-chain (antibungarotoxin) antibodies. It also cross-reacted with antimyotoxic PLA2 antibodies from M. nigrocinctus nigrocinctus (antinigroxin). Our results point to the need of catalytic activity for these venoms to exert their neurotoxic activity efficiently and to their components as attractive tools for the study of molecular targets on cell membranes.

  16. Secreted phospholipase A2-IIA-induced a phenotype of activated microglia in BV-2 cells requires epidermal growth factor receptor transactivation and proHB-EGF shedding

    PubMed Central

    2012-01-01

    Background Activation of microglia, the primary component of the innate immune response in the brain, is a hallmark of neuroinflammation in neurodegenerative disorders, including Alzheimer’s disease (AD) and other pathological conditions such as stroke or CNS infection. In response to a variety of insults, microglial cells produce high levels of inflammatory cytokines that are often involved in neuronal injury, and play an important role in the recognition, engulfment, and clearance of apoptotic cells and/or invading microbes. Secreted phospholipase A2-IIA (sPLA2-IIA), an enzyme that interacts with cells involved in the systemic immune/inflammatory response, has been found up-regulated in the cerebrospinal fluid and brain of AD patients. However, despite several approaches, its functions in mediating CNS inflammation remain unknown. In the present study, the role of sPLA2-IIA was examined by investigating its direct effects on microglial cells. Methods Primary and immortalized microglial cells were stimulated by sPLA2-IIA in order to characterize the cytokine-like actions of the phospholipase. The hallmarks of activated microglia analyzed include: mitogenic response, phagocytic capabilities and induction of inflammatory mediators. In addition, we studied several of the potential molecular mechanisms involved in those events. Results The direct exposure of microglial cells to sPLA2-IIA stimulated, in a time- and dose-dependent manner, their phagocytic and proliferative capabilities. sPLA2-IIA also triggered the synthesis of the inflammatory proteins COX-2 and TNFα. In addition, EGFR phosphorylation and shedding of the membrane-anchored heparin-binding EGF-like growth factor (pro-HB-EGF) ectodomain, as well as a rapid activation/phosphorylation of the classical survival proteins ERK, P70S6K and rS6 were induced upon sPLA2-IIA treatment. We further demonstrated that the presence of an EGFR inhibitor (AG1478), a matrix metalloproteinase inhibitor (GM6001), an ADAM

  17. Inhibition of Cytosolic Phospholipase A2α (cPLA2α) by Medicinal Plants in Relation to Their Phenolic Content.

    PubMed

    Arnold, Eva; Benz, Thorsten; Zapp, Cornelia; Wink, Michael

    2015-01-01

    The cytosolic phospholipase A2α(cPLA2α) is one of the potential targets for anti-inflammatory drugs, since this enzyme plays a key role in the inflammation processes seen in health disorders, like asthma, allergic reactions, arthritis and neuronal diseases. In this study, cPLA2α inhibition by 43 methanol extracts from medicinal plants rich in polyphenols was determined. The eight most active extracts were derived from Ribes nigrum (IC50 of 27.7 μg/mL), Ononis spinosa (IC50 of 39.4 μg/mL), Urtica dioica (IC50 of 44.32 μg/mL), Betula sp. (IC50 of 58.02 μg/mL), Sanguisorba officinalis (IC50 of 76.25 μg/mL), Orthosiphon stamineus (IC50 of 78.83 μg/mL), Petasites hybridus (IC50 of 81.02 μg/mL) and Tussilago farfara (IC50 of 123.28 μg/mL). Additionally, the antioxidant activities of these extracts were determined with the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay and their phenolic content with the Folin-Ciocalteu reagent. Antioxidant activity showed a non-linear, positive correlation to the phenolic content, but no correlation of PLA2 inhibition with phenolic content could be established. This study provides evidence that cPLA2α may be a relevant target for anti-inflammatory agents. PMID:26287155

  18. Antitumoral Activity of Snake Venom Proteins: New Trends in Cancer Therapy

    PubMed Central

    Calderon, Leonardo A.; Sobrinho, Juliana C.; Zaqueo, Kayena D.; de Moura, Andrea A.; Grabner, Amy N.; Mazzi, Maurício V.; Marcussi, Silvana; Fernandes, Carla F. C.; Zuliani, Juliana P.; Carvalho, Bruna M. A.; da Silva, Saulo L.; Stábeli, Rodrigo G.; Soares, Andreimar M.

    2014-01-01

    For more than half a century, cytotoxic agents have been investigated as a possible treatment for cancer. Research on animal venoms has revealed their high toxicity on tissues and cell cultures, both normal and tumoral. Snake venoms show the highest cytotoxic potential, since ophidian accidents cause a large amount of tissue damage, suggesting a promising utilization of these venoms or their components as antitumoral agents. Over the last few years, we have studied the effects of snake venoms and their isolated enzymes on tumor cell cultures. Some in vivo assays showed antineoplastic activity against induced tumors in mice. In human beings, both the crude venom and isolated enzymes revealed antitumor activities in preliminary assays, with measurable clinical responses in the advanced treatment phase. These enzymes include metalloproteases (MP), disintegrins, L-amino acid oxidases (LAAOs), C-type lectins, and phospholipases A2 (PLA2s). Their mechanisms of action include direct toxic action (PLA2s), free radical generation (LAAOs), apoptosis induction (PLA2s, MP, and LAAOs), and antiangiogenesis (disintegrins and lectins). Higher cytotoxic and cytostatic activities upon tumor cells than normal cells suggest the possibility for clinical applications. Further studies should be conducted to ensure the efficacy and safety of different snake venom compounds for cancer drug development. PMID:24683541

  19. Comparative studies on the inhibitory activities of selected benzoic acid derivatives against secretory phospholipase A2, a key enzyme involved in the inflammatory pathway.

    PubMed

    Dileep, K V; Remya, C; Cerezo, J; Fassihi, A; Pérez-Sánchez, H; Sadasivan, C

    2015-07-01

    Inflammation is considered to be a key factor in major diseases like cancer, Alzheimer's disease, Parkinson's disease, etc. For the past few decades, pharmaceutical companies have explored new effective medications against inflammation. As a part of their detailed studies, many drug targets and drugs have been introduced against inflammation. In the present study, the inhibiting capacities of selected benzoic acid derivatives like gallic acid, vannilic acid, syringic acid and protocatechuic acid against secretory phospholipase A2 (sPLA2), a major enzyme involved in the inflammatory pathway, have been investigated. The detailed in vitro, biophysical and in silico studies carried out on these benzoic acid derivatives revealed that all the selected compounds have a uniform mode of binding in the active site of sPLA2 and are inhibitory in micromolar concentrations. The study also focuses on the non-selective inhibitory activity of an NSAID, aspirin, against sPLA2.

  20. Antimutagenic activity of spearmint.

    PubMed

    Yu, Tian-Wei; Xu, Meirong; Dashwood, Roderick H

    2004-01-01

    The antimutagenic activity of spearmint (Mentha spicata), a popular food flavoring agent, was studied in the Salmonella assay. Spearmint leaves were brewed in hot water for 5 min at concentrations up to 5% (w/v), and the water extracts were tested against the direct-acting mutagens 4-nitro-1,2-phenylenediamine (NPD) and 2-hydroxyamino-3-methyl-3H-imidazo[4,5-f]quinoline (N-OH-IQ) using Salmonella typhimurium strain TA98. Nontoxic concentrations of spearmint extract inhibited the mutagenic activity of N-OH-IQ in a concentration-dependent fashion, but had no effect against NPD. These experiments by design focused on the water extract consumed commonly as an herbal tea, but chloroform and methanol extracts of spearmint also possessed antimutagenic activity against N-OH-IQ. Water extract of spearmint inhibited the mutagenic activity of the parent compound, 2-amino-3-methyl-3H-imidazo[4,5-f]quinoline (IQ), in the presence of rat liver S9; however, the concentration for 50% inhibition (IC50) against IQ was approximately 10-fold higher than in assays with N-OH-IQ minus S9. At concentrations similar to those used in the Salmonella assays, spearmint extract inhibited two of the major enzymes that play a role in the metabolic activation of IQ, namely, cytochromes P4501A1 and 1A2, based on ethoxyresorufin O-deethylase and methoxyresorufin O-demethylase assays in vitro. In vivo, rats were given spearmint water extract (2%; w/v) as the sole source of drinking fluid before, during, and after 2-week treatment with IQ; colonic aberrant crypt foci were inhibited significantly at 8 weeks (P < 0.05, compared with rats given IQ alone). Collectively, these findings suggest that spearmint tea protects against IQ and possibly other heterocyclic amines through inhibition of carcinogen activation and via direct effects on the activated metabolite(s).

  1. PLA-PEG-PLA and its electroactive tetraaniline copolymer as multi-interactive injectable hydrogels for tissue engineering.

    PubMed

    Cui, Haitao; Shao, Jun; Wang, Yu; Zhang, Peibiao; Chen, Xuesi; Wei, Yen

    2013-06-10

    Injectable hydrogels have served as biomimic scaffolds that provide a three-dimensional (3D) structure for tissue engineering or carriers for cell encapsulation in the biomedical field. In this study, the injectable electroactive hydrogels (IEHs) were prepared by introducing electrical properties into the injectable materials. Carboxyl-capped tetraaniline (CTA) as functional group was coupled with enantiomeric polylactide-poly(ethylene glycol)-polylactide (PLA-PEG-PLA), and the electroactive hydrogels were obtained by mixing the enantiomeric copolymers of CTA-PLLA-PEG-PLLA-CTA and CTA-PDLA-PEG-PDLA-CTA aqueous solutions. ultraviolet-visible spectroscopy (UV-vis) and cyclic voltammetry (CV) of the complex solution showed good electroactive properties. The gelation mechanism and intermolecular multi-interactions such as stereocomplextion, hydrogen bonding, and π-π stacking were studied by Fourier transform infrared spectroscopy (FT-IR), UV-vis, and wide-angle X-ray diffraction (WAXD). Gelation properties of the complexes were also studied by rheometer. The encapsulated cells remained highly viable in the gel matrices, suggesting that the hydrogels have excellent cytocompatibility. After subcutaneous injection, the gels were formed in situ in the subcutaneous layer, and hematoxylin-eosin (H&E) staining suggested acceptable biocompatibility of our materials in vivo. Moreover, these injectable materials, when treated with pulsed electrical stimuli, were shown to be functionally active and to accelerate the proliferation of encapsulated fibroblasts, cardiomyocytes, and osteoblasts. Hence, the IEHs possessing these excellent properties would be potentially used as in vivo materials for tissue engineering scaffold. PMID:23611017

  2. Walkability and Physical Activity

    PubMed Central

    Reis, Rodrigo Siqueira; Hino, Adriano Akira Ferreira; Rech, Cassiano Ricardo; Kerr, Jacqueline; Hallal, Pedro Curi

    2013-01-01

    Background Evidence from developing countries is limited on how income level for a given neighborhood is related to physical activity among its residents. Purpose The goal of the study was to examine the association between walkability and physical activity outcomes, and the effect of income on the relationship between walkability and physical activity in adults. Methods The Spaces for Physical Activity in Adults Study (ESPACOS Project) took place in Curitiba, Brazil. Data were collected in 2010 in 32 census tracts selected to vary in income and walkability, as measured by GIS. Participants were 697 individuals aged 18–65 years (52.0% were women) randomly sampled from the selected neighborhoods. The International Physical Activity Questionnaire was used to measure physical activity. All analyses were conducted in 2012. Results The proportion of those who walked for transportation for ≥150 minutes/week was 21.1% in low-walkability areas, and ranged from 33.5% to 35.0% in high-walkability areas. A total of 12.6% of residents were found to walk for leisure for ≥150 minutes/week; this result did not vary across quadrants of walkability and income level. The prevalence of leisure-time moderate-to-vigorous physical activity (MVPA) was 7.1–10.5 percentage points higher in high-compared to low-walkability areas. After adjusting for all individual confounders, walkability showed an independent association with walking for transport (OR=2.10, 95% CI=1.31, 3.37, p=0.002) and leisure-time MVPA (OR=1.57; 95% CI=1.06, 2.32; p=0.024). Neighborhood income level was independently associated with leisure-time MVPA (OR=1.70; 95% CI=1.06, 2.74, p=0.029). No association was found between walkability and walking for leisure. No interaction was found between walkability and neighborhood income level. Conclusions This study, among adults living in Curitiba, Brazil, confirms findings from studies of high-income countries showing that walkability is positively associated with

  3. Mechanochemically Active Soft Robots.

    PubMed

    Gossweiler, Gregory R; Brown, Cameron L; Hewage, Gihan B; Sapiro-Gheiler, Eitan; Trautman, William J; Welshofer, Garrett W; Craig, Stephen L

    2015-10-14

    The functions of soft robotics are intimately tied to their form-channels and voids defined by an elastomeric superstructure that reversibly stores and releases mechanical energy to change shape, grip objects, and achieve complex motions. Here, we demonstrate that covalent polymer mechanochemistry provides a viable mechanism to convert the same mechanical potential energy used for actuation in soft robots into a mechanochromic, covalent chemical response. A bis-alkene functionalized spiropyran (SP) mechanophore is cured into a molded poly(dimethylsiloxane) (PDMS) soft robot walker and gripper. The stresses and strains necessary for SP activation are compatible with soft robot function. The color change associated with actuation suggests opportunities for not only new color changing or camouflaging strategies, but also the possibility for simultaneous activation of latent chemistry (e.g., release of small molecules, change in mechanical properties, activation of catalysts, etc.) in soft robots. In addition, mechanochromic stress mapping in a functional robotic device might provide a useful design and optimization tool, revealing spatial and temporal force evolution within the robot in a way that might be coupled to autonomous feedback loops that allow the robot to regulate its own activity. The demonstration motivates the simultaneous development of new combinations of mechanophores, materials, and soft, active devices for enhanced functionality.

  4. Photon-activation therapy

    SciTech Connect

    Fairchild, R.G.; Bond, V.P.

    1982-01-01

    Photon Activation Therapy (PAT) is a technique in which radiation dose to tumor is enhanced via introduction of stable /sup 127/I in the form of iodinated deoxyuridine (IdUrd). Stimulation of cytotoxic effects from IdUrd is accomplished by activation with external (or implanted) radiation sources. Thus, accumulations of this nucleoside in actively competing cellpools do not preclude therapy in so far as such tissues can be excluded from the radiation field. Calculations show that 5% replacement of thymidine (Tyd) in tumor DNA should enhance the biological effectiveness of a given photon radiotherapy dose by a factor of approx. 3. Proportionally higher gains would result from higher replacements of Tyd and IdUrd. In addition, biological response is enhanced by chemical sensitization with IdUrd. The data indicate that damage from photon activation as well as chemical sensitization does not repair. Thus, at low dose rates, a further increase in therapeutic gain should accrue as normal tissues are allowed to repair and regenerate. A samarium-145 source has been developed for PAT, with activating x-ray energies of from 38 to 45 keV. Favorable clinical results can be expected through the use of IdUrd and protracted irradiations with low energy x-rays. In particular, PAT may provide unique advantages at selected sites such as brain, or head and neck tumors. (ERB)

  5. Mechanochemically Active Soft Robots.

    PubMed

    Gossweiler, Gregory R; Brown, Cameron L; Hewage, Gihan B; Sapiro-Gheiler, Eitan; Trautman, William J; Welshofer, Garrett W; Craig, Stephen L

    2015-10-14

    The functions of soft robotics are intimately tied to their form-channels and voids defined by an elastomeric superstructure that reversibly stores and releases mechanical energy to change shape, grip objects, and achieve complex motions. Here, we demonstrate that covalent polymer mechanochemistry provides a viable mechanism to convert the same mechanical potential energy used for actuation in soft robots into a mechanochromic, covalent chemical response. A bis-alkene functionalized spiropyran (SP) mechanophore is cured into a molded poly(dimethylsiloxane) (PDMS) soft robot walker and gripper. The stresses and strains necessary for SP activation are compatible with soft robot function. The color change associated with actuation suggests opportunities for not only new color changing or camouflaging strategies, but also the possibility for simultaneous activation of latent chemistry (e.g., release of small molecules, change in mechanical properties, activation of catalysts, etc.) in soft robots. In addition, mechanochromic stress mapping in a functional robotic device might provide a useful design and optimization tool, revealing spatial and temporal force evolution within the robot in a way that might be coupled to autonomous feedback loops that allow the robot to regulate its own activity. The demonstration motivates the simultaneous development of new combinations of mechanophores, materials, and soft, active devices for enhanced functionality. PMID:26390078

  6. 20(S)-Protopanaxatriol inhibits release of inflammatory mediators in immunoglobulin E-mediated mast cell activation

    PubMed Central

    Kim, Dae Yong; Ro, Jai Youl; Lee, Chang Ho

    2014-01-01

    Background Antiallergic effect of 20(S)-protopanaxatriol (PPT), an intestinal metabolite of ginseng saponins, was investigated in guinea pig lung mast cells and mouse bone marrow-derived mast cells activated by a specific antigen/antibody reaction. Methods Increasing concentrations of PPT were pretreated 5 min prior to antigen stimulation, and various inflammatory mediator releases and their relevant cellular signaling events were measured in those cells. Results PPT dose-dependently reduced the release of histamine and leukotrienes in both types of mast cells. Especially, in activated bone marrow-derived mast cells, PPT inhibited the expression of Syk protein, cytokine mRNA, cyclooxygenase-1/2, and phospholipase A2 (PLA2), as well as the activities of various protein kinase C isoforms, mitogen-activated protein kinases, PLA2, and transcription factors (nuclear factor-κB and activator protein-1). Conclusion PPT reduces the release of inflammatory mediators via inhibiting multiple cellular signaling pathways comprising the Ca2+ influx, protein kinase C, and PLA2, which are propagated by Syk activation upon allergic stimulation of mast cells. PMID:26199549

  7. Prenucleosomes and Active Chromatin

    PubMed Central

    Khuong, Mai T.; Fei, Jia; Ishii, Haruhiko; Kadonaga, James T.

    2016-01-01

    Chromatin consists of nucleosomes as well as nonnucleosomal histone-containing particles. Here we describe the prenucleosome, which is a stable conformational isomer of the nucleosome that associates with ~80 bp DNA. Prenucleosomes are formed rapidly upon the deposition of histones onto DNA and can be converted into canonical nucleosomes by an ATP-driven chromatin assembly factor such as ACF. Different lines of evidence reveal that there are prenucleosome-sized DNA-containing particles with histones in the upstream region of active promoters. Moreover, p300 acetylates histone H3K56 in prenucleosomes but not in nucleosomes, and H3K56 acetylation is found at active promoters and enhancers. These findings therefore suggest that there may be prenucleosomes or prenucleosome-like particles in the upstream region of active promoters. More generally, we postulate that prenucleosomes or prenucleosome-like particles are present at dynamic chromatin, whereas canonical nucleosomes are at static chromatin. PMID:26767995

  8. [Physical activity and obesity].

    PubMed

    Winkler, S; Hebestreit, A; Ahrens, W

    2012-01-01

    One reason for the high prevalence of overweight and obesity might be the differences in lifestyle compared to earlier decades, called the "obesogenic environment." With this, the decline in physical activity (PA) in favor of a sedentary lifestyle is assumed to play an important role. Physical activity or inactivity has a major impact on the development of overweight and obesity as well as on certain metabolic disorders. This review summarizes current scientific knowledge regarding the association between PA and overweight/obesity. The term "physical activity" is defined and different methods of its assessment are introduced. In addition, certain methods for the evaluation/operationalization of collected PA data are described. Finally, some epidemiological studies dealing with the associations between PA and overweight/obesity in children/adolescents as well as in adults are presented.

  9. Shared Activity Coordination

    NASA Technical Reports Server (NTRS)

    Clement, Bradley J.; Barrett, Anthony C.

    2003-01-01

    Interacting agents that interleave planning and execution must reach consensus on their commitments to each other. In domains where agents have varying degrees of interaction and different constraints on communication and computation, agents will require different coordination protocols in order to efficiently reach consensus in real time. We briefly describe a largely unexplored class of real-time, distributed planning problems (inspired by interacting spacecraft missions), new challenges they pose, and a general approach to solving the problems. These problems involve self-interested agents that have infrequent communication but collaborate on joint activities. We describe a Shared Activity Coordination (SHAC) framework that provides a decentralized algorithm for negotiating the scheduling of shared activities in a dynamic environment, a soft, real-time approach to reaching consensus during execution with limited communication, and a foundation for customizing protocols for negotiating planner interactions. We apply SHAC to a realistic simulation of interacting Mars missions and illustrate the simplicity of protocol development.

  10. In Vitro Antiplasmodial Activity of Phospholipases A2 and a Phospholipase Homologue Isolated from the Venom of the Snake Bothrops asper

    PubMed Central

    Castillo, Juan Carlos Quintana; Vargas, Leidy Johana; Segura, Cesar; Gutiérrez, José María; Pérez, Juan Carlos Alarcón

    2012-01-01

    The antimicrobial and antiparasite activity of phospholipase A2 (PLA2) from snakes and bees has been extensively explored. We studied the antiplasmodial effect of the whole venom of the snake Bothrops asper and of two fractions purified by ion-exchange chromatography: one containing catalytically-active phospholipases A2 (PLA2) (fraction V) and another containing a PLA2 homologue devoid of enzymatic activity (fraction VI). The antiplasmodial effect was assessed on in vitro cultures of Plasmodium falciparum. The whole venom of B. asper, as well as its fractions V and VI, were active against the parasite at 0.13 ± 0.01 µg/mL, 1.42 ± 0.56 µg/mL and 22.89 ± 1.22 µg/mL, respectively. Differences in the cytotoxic activity on peripheral blood mononuclear cells between the whole venom and fractions V and VI were observed, fraction V showing higher toxicity than total venom and fraction VI. Regarding toxicity in mice, the whole venom showed the highest lethal effect in comparison to fractions V and VI. These results suggest that B. asper PLA2 and its homologue have antiplasmodial potential. PMID:23242318

  11. In vitro antiplasmodial activity of phospholipases A2 and a phospholipase homologue isolated from the venom of the snake Bothrops asper.

    PubMed

    Castillo, Juan Carlos Quintana; Vargas, Leidy Johana; Segura, Cesar; Gutiérrez, José María; Pérez, Juan Carlos Alarcón

    2012-12-01

    The antimicrobial and antiparasite activity of phospholipase A(2) (PLA(2)) from snakes and bees has been extensively explored. We studied the antiplasmodial effect of the whole venom of the snake Bothrops asper and of two fractions purified by ion-exchange chromatography: one containing catalytically-active phospholipases A(2) (PLA(2)) (fraction V) and another containing a PLA(2) homologue devoid of enzymatic activity (fraction VI). The antiplasmodial effect was assessed on in vitro cultures of Plasmodium falciparum. The whole venom of B. asper, as well as its fractions V and VI, were active against the parasite at 0.13 ± 0.01 µg/mL, 1.42 ± 0.56 µg/mL and 22.89 ± 1.22 µg/mL, respectively. Differences in the cytotoxic activity on peripheral blood mononuclear cells between the whole venom and fractions V and VI were observed, fraction V showing higher toxicity than total venom and fraction VI. Regarding toxicity in mice, the whole venom showed the highest lethal effect in comparison to fractions V and VI. These results suggest that B. asper PLA(2) and its homologue have antiplasmodial potential. PMID:23242318

  12. Stochastic optical active rheology

    NASA Astrophysics Data System (ADS)

    Lee, Hyungsuk; Shin, Yongdae; Kim, Sun Taek; Reinherz, Ellis L.; Lang, Matthew J.

    2012-07-01

    We demonstrate a stochastic based method for performing active rheology using optical tweezers. By monitoring the displacement of an embedded particle in response to stochastic optical forces, a rapid estimate of the frequency dependent shear moduli of a sample is achieved in the range of 10-1-103 Hz. We utilize the method to probe linear viscoelastic properties of hydrogels at varied cross-linker concentrations. Combined with fluorescence imaging, our method demonstrates non-linear changes of bond strength between T cell receptors and an antigenic peptide due to force-induced cell activation.

  13. SCOR announces new activities

    NASA Astrophysics Data System (ADS)

    Urban, Edward R., Jr.

    Roger Revelle had many good ideas during his long and productive career. One of them came to fruition in 1957 in the form of the Scientific Committee on Oceanic Research (SCOR), which the International Council for Science created as its first interdisciplinary body, to promote international activities in oceanography. Revelle served as SCOR's first president from 1957 to 1960. SCOR offers opportunities for scientists from different countries to cooperate in planning and executing international programs in ocean sciences. Over its 44 years in existence, SCOR has sponsored 120 working groups and has actively participated in many of the major international oceanographic projects. Thirty-six nations presently participate as SCOR members.

  14. Active cleaning technique device

    NASA Technical Reports Server (NTRS)

    Shannon, R. L.; Gillette, R. B.

    1973-01-01

    The objective of this program was to develop a laboratory demonstration model of an active cleaning technique (ACT) device. The principle of this device is based primarily on the technique for removing contaminants from optical surfaces. This active cleaning technique involves exposing contaminated surfaces to a plasma containing atomic oxygen or combinations of other reactive gases. The ACT device laboratory demonstration model incorporates, in addition to plasma cleaning, the means to operate the device as an ion source for sputtering experiments. The overall ACT device includes a plasma generation tube, an ion accelerator, a gas supply system, a RF power supply and a high voltage dc power supply.

  15. Cosmogenic activation of materials

    SciTech Connect

    Amare, J.; Beltran, B.; Carmona, J.M.; Cebrian, S.; Garcia, E.; Irastorza, I.G.; Gomez, H.; Luzon, G.; Martinez, M.; Morales, J.; Ortiz de Solorzano, A.; Pobes, C.; Puimedon, J.; Rodriguez, A.; Ruz, J.; Sarsa, M. L.; Torres, L.; Villar, J.A.; Capelli, S.; Capozzi, F.

    2005-09-08

    The problem of cosmogenic activation produced at sea level in materials typically used in underground experiments looking for rare events is being studied. Several nuclear data libraries have been screened looking for relevant isotope production cross-sections and different codes which can be applied to activation studies have been reviewed. The excitation functions for some problems of interest like production of 60Co and 68Ge in germanium and production of 60Co in tellurium have been obtained taking into account both measurements and calculations and a preliminary estimate of the corresponding rates of production at sea level has been performed.

  16. Optical activity and evolution.

    PubMed

    Khasanov, M M; Gladyshev, G P

    1980-09-01

    It is noted that the chemical reactions occurring in rarefied cosmic clouds (molecular concentration less than or approximately to 10(2) cm-3) differ from similar laboratory reactions by the much greater effect on the outcome of external force fields. In this light it is hypothesized that the synthesis of optically active substances may occur in the outer space under the conjoint stereospecific effect of a magnetic and other molecule-orienting field. It is further conjectured that the optically active substances of the Solar System had been produced in the course of its formation out of the primal rarefield cloud.

  17. Activated carbon material

    DOEpatents

    Evans, A. Gary

    1978-01-01

    Activated carbon particles for use as iodine trapping material are impregnated with a mixture of selected iodine and potassium compounds to improve the iodine retention properties of the carbon. The I/K ratio is maintained at less than about 1 and the pH is maintained at above about 8.0. The iodine retention of activated carbon previously treated with or coimpregnated with triethylenediamine can also be improved by this technique. Suitable flame retardants can be added to raise the ignition temperature of the carbon to acceptable standards.

  18. Inflammasomes and Their Activation

    PubMed Central

    Khare, Sonal; Luc, Nancy; Dorfleutner, Andrea; Stehlik, Christian

    2011-01-01

    The innate immune system relies on the recognition of pathogens by pattern recognition receptors as a first line of defense and to initiate the adaptive immune response. Substantial progress has been made in defining the role of Nod (nucleotide-binding oligimerization domain)-like receptors and AIM2 (absent in melanoma 2) as pattern recognition receptors that activate inflammasomes in macrophages. Inflammasomes are protein platforms essential for the activation of inflammatory caspases and subsequent maturation of their pro-inflammatory cytokine substrates and induction of pyroptosis. This paper summarizes recent developments regarding the function of Nod-like receptors in immunity and disease. PMID:21083527

  19. Space construction activities

    NASA Technical Reports Server (NTRS)

    1991-01-01

    The Center for Space Construction at the University of Colorado at Boulder was established in 1988 as a University Space Engineering Research Center. The mission of the Center is to conduct interdisciplinary engineering research which is critical to the construction of future space structures and systems and to educate students who will have the vision and technical skills to successfully lead future space construction activities. The research activities are currently organized around two central projects: Orbital Construction and Lunar Construction. Summaries of the research projects are included.

  20. Active seismic experiment

    NASA Technical Reports Server (NTRS)

    Kovach, R. L.; Watkins, J. S.; Talwani, P.

    1972-01-01

    The Apollo 16 active seismic experiment (ASE) was designed to generate and monitor seismic waves for the study of the lunar near-surface structure. Several seismic energy sources are used: an astronaut-activated thumper device, a mortar package that contains rocket-launched grenades, and the impulse produced by the lunar module ascent. Analysis of some seismic signals recorded by the ASE has provided data concerning the near-surface structure at the Descartes landing site. Two compressional seismic velocities have so far been recognized in the seismic data. The deployment of the ASE is described, and the significant results obtained are discussed.

  1. [Adolescents' physical activity].

    PubMed

    Pagaeva, E K; Misho, P -A; Zhanin, A; Chanturishvili, T P; Pagaeva, K I

    2006-01-01

    The paper defines the parameters reflecting the physical activity of adolescents and their correlation with health and a risk of behavioral disorders, bad habits, and cravings. A total of 9499 Georgian adolescents aged 14-18 years, the senior (9th-llth-form) pupils, selected through two-step cluster sampling were surveyed. The pupils anonymously filled in special questionnaires. This yielded the parameters reflecting the intensity of physical activity of the adolescents and the latter's going in for sports. The parameters were shown to have a beneficial effect on health, including mental health, and on the magnitude of unhealthy behavior.

  2. EPAct Transportation Regulatory Activities

    SciTech Connect

    2011-11-21

    The U.S. Department of Energy's (DOE) Vehicle Technologies Program manages several transportation regulatory activities established by the Energy Policy Act of 1992 (EPAct), as amended by the Energy Conservation Reauthorization Act of 1998, EPAct 2005, and the Energy Independence and Security Act of 2007 (EISA).

  3. Active-bridge oscillator

    DOEpatents

    Wessendorf, Kurt O.

    2001-01-01

    An active bridge oscillator is formed from a differential amplifier where positive feedback is a function of the impedance of one of the gain elements and a relatively low value common emitter resistance. This use of the nonlinear transistor parameter h stabilizes the output and eliminates the need for ALC circuits common to other bridge oscillators.

  4. Antifungal activity of diethyldithiocarbamate.

    PubMed

    Allerberger, F; Reisinger, E C; Söldner, B; Dierich, M P

    1989-10-01

    Sodium diethyldithiocarbamate (DTC) was evaluated for its ability to combat four different species of fungi in vitro. Using a microtiter-broth-dilution method we were able to demonstrate an antifungal activity against Candida albicans, Cryptococcus neoformans, Aspergillus fumigatus and Mucor mucedo in doses achievable by intravenous administration in man.

  5. Activities of the ILO.

    ERIC Educational Resources Information Center

    Labour Education, 1986

    1986-01-01

    Discusses the Workers' Education Branch of the ILO (International Labour Organisation), which has been developing workers' education activities in Africa, Asia, and Latin America for the purpose of assisting rural workers' organizations in identifying and developing plans to overcome their own major organizational and financial problems. (CT)

  6. Activities of the ILO.

    ERIC Educational Resources Information Center

    Enevoldsen, Niels; And Others

    1981-01-01

    A series of articles reviews educational activities of the International Labour Organisation (ILO), including international seminars on workers' education, a study of women workers, trade union training courses at the ILO Turin Centre, and the importance of information dissemination to trade unions. (SK)

  7. Valuing Families. Activity Guide.

    ERIC Educational Resources Information Center

    Glashagel, Jerry; Glashagel, Char

    Developed as a resource for family life education, this activity guide can be used to lead experiential learning situations for intergenerational groups by a counselor, in a course, in a family organization like the YMCA, or in the home. The goals of this guide are to increase the self-esteem of each person and to strengthen the family as a human…

  8. Classroom Speaking Activities.

    ERIC Educational Resources Information Center

    Shuying, Yang

    1999-01-01

    Because most language teaching in China is focused on national tests, language is treated as a knowledge subject and development of communicative abilities is often ignored. This article describes activities that one English-as-a-Foreign-Language teacher used to teach oral English to university students in China. (Author/VWL)

  9. Ocean Drilling Simulation Activity.

    ERIC Educational Resources Information Center

    Telese, James A.; Jordan, Kathy

    The Ocean Drilling Project brings together scientists and governments from 20 countries to explore the earth's structure and history as it is revealed beneath the oceans' basins. Scientific expeditions examine rock and sediment cores obtained from the ocean floor to learn about the earth's basic processes. The series of activities in this…

  10. Physical Education Activities

    ERIC Educational Resources Information Center

    Russo, Letty P.

    1978-01-01

    Described are three physical activity games designed to help young children develop a sense of mastery over their bodies: (which will in turn improve their self concepts): a poem to be acted out, Simon Says, and a story play to be acted out. (DLS)

  11. Sexual activity and aging.

    PubMed

    Ni Lochlainn, Mary; Kenny, Rose Anne

    2013-08-01

    Sexuality is an important component of emotional and physical intimacy that men and women experience throughout their lives. Research suggesting that a high proportion of men and women remain sexually active well into later life refutes the prevailing myth that aging and sexual dysfunction are inexorably linked. Age-related physiological changes do not render a meaningful sexual relationship impossible or even necessarily difficult. Many of these physiological changes are modifiable. There are various therapeutic options available to patients to achieve maximum sexual capacity in old age. This article reviews the prevalence of sexual activity among older adults, the problems these adults encounter with sexual activity, and the role of the health care professional in addressing these problems. The physiological sex-related changes that occur as part of the normal aging process in men and women are reviewed, as well as the effect of age-related physical and psychological illness on sexual function. The attitudes and perceptions of the media and general public toward sexual activity and aging are summarized. An understanding of the sexual changes that accompany the aging process may help general practitioners and other doctors to give practical and useful advice on sexuality as well as refute the misconception that aging equates to celibacy. A thorough awareness of this aspect of older people's quality of life can raise meaningful expectations for aging patients. PMID:23540950

  12. Discovering Columbus: Classroom Activities.

    ERIC Educational Resources Information Center

    Moulden, Rick

    1992-01-01

    Presents learning activities concerning Christopher Columbus and his voyages. Includes lessons requiring students to (1) write a pledge of allegiance to the world; (2) examine the Americas before Columbus; (3) prepare a newscast on Columbus' arrival in the Americas; (4) imagine being a Native American encountering Columbus; and (5) explore what…

  13. Nutrition. Learning Activity Package.

    ERIC Educational Resources Information Center

    Lee, Carolyn

    This learning activity package on nutrition is one of a series of 12 titles developed for use in health occupations education programs. Materials in the package include objectives, a list of materials needed, a list of definitions, information sheets, reviews (self evaluations) of portions of the content, and answers to reviews. These topics are…

  14. Highlights of 1978 activities

    NASA Technical Reports Server (NTRS)

    1978-01-01

    General highlights of NASA's activities for 1978 are presented. The highlights are categorized into topics such as space science, space transportation systems, space and terrestrial applications, environment, technology utilization, aeronautics, space research and technology, energy programs, and international. A list of the 1978 launches including: (1) launch date; (2) payload designation; (3) launch vehicle; (4) launch site and (5) mission remarks is also presented.

  15. Arsenic activation neutron detector

    DOEpatents

    Jacobs, E.L.

    1980-01-28

    A detector of bursts of neutrons from a deuterium-deuteron reaction includes a quantity of arsenic adjacent a gamma detector such as a scintillator and photomultiplier tube. The arsenic is activated by the 2.5-MeV neutrons to release gamma radiation which is detected to give a quantitative representation of detected neutrons.

  16. Arsenic activation neutron detector

    DOEpatents

    Jacobs, Eddy L.

    1981-01-01

    A detector of bursts of neutrons from a deuterium-deuteron reaction includes a quantity of arsenic adjacent a gamma detector such as a scintillator and photomultiplier tube. The arsenic is activated by the 2.5 Mev neutrons to release gamma radiation which is detected to give a quantitative representation of detected neutrons.

  17. Activating silent argonautes.

    PubMed

    Kidwell, Mary Anne; Doudna, Jennifer A

    2013-07-01

    Multiple Argonaute proteins are implicated in gene silencing by RNA interference (RNAi), but only one is known to be an endonuclease that can cleave target mRNAs. Chimeric Argonaute proteins now reveal an unexpected mechanism by which mutations distal to the catalytic center can unmask intrinsic catalytic activity, results hinting at structurally mediated regulation. PMID:23984440

  18. Highlights of 1976 activities

    NASA Technical Reports Server (NTRS)

    Fitzpatrick, M.

    1976-01-01

    Highlights of NASA's 1976 activities are summarized. Sixteen successful launches were made. Two landings of Viking spacecraft on Mars and rollout of the space shuttle orbiter are reviewed. Applications of aerospace science to education, health care, and community services are also discussed.

  19. Educating for Political Activity

    ERIC Educational Resources Information Center

    Chitty, Clyde

    2010-01-01

    The term "political activity" can be interpreted in a myriad of different ways, but in this paper, it is taken to mean involvement in a variety of campaigns around issues affecting the way we live and the sort of society we want to live in. At a time when support for the main political parties has never been weaker, it is essential that teachers…

  20. Geology: The Active Earth.

    ERIC Educational Resources Information Center

    Braus, Judy, Ed.

    1987-01-01

    Ranger Rick's NatureScope is a creative education series dedicated to inspiring in children an understanding and appreciation of the natural world while developing the skills they will need to make responsible decisions about the environment. The topic of this issue is "Geology: The Active Earth." Contents are organized into the following…

  1. Environmental Chemistry Activities.

    ERIC Educational Resources Information Center

    Jackland, Thomas; And Others

    The authors of this curriculum supplement believe in a laboratory approach to chemistry and express the feeling that environmental chemistry provides the students an opportunity to apply theoretical chemistry to important practical problems. There are eighteen activities presented, each accompanied with behavioral objectives, one or more suggested…

  2. Regional Activities Division. Papers.

    ERIC Educational Resources Information Center

    International Federation of Library Associations, The Hague (Netherlands).

    Papers on library network activities in Canada, the Third World, Japan, Malaysia, Brazil, and Sweden which were presented at the 1982 International Federation of Library Associations (IFLA) conference include: (1) "Canada: A Voluntary and Flexible Network," a review by Guy Sylvestre of the political, social, and economic structures affecting…

  3. Classification of Physical Activity

    PubMed Central

    Turksoy, Kamuran; Paulino, Thiago Marques Luz; Zaharieva, Dessi P.; Yavelberg, Loren; Jamnik, Veronica; Riddell, Michael C.; Cinar, Ali

    2015-01-01

    Physical activity has a wide range of effects on glucose concentrations in type 1 diabetes (T1D) depending on the type (ie, aerobic, anaerobic, mixed) and duration of activity performed. This variability in glucose responses to physical activity makes the development of artificial pancreas (AP) systems challenging. Automatic detection of exercise type and intensity, and its classification as aerobic or anaerobic would provide valuable information to AP control algorithms. This can be achieved by using a multivariable AP approach where biometric variables are measured and reported to the AP at high frequency. We developed a classification system that identifies, in real time, the exercise intensity and its reliance on aerobic or anaerobic metabolism and tested this approach using clinical data collected from 5 persons with T1D and 3 individuals without T1D in a controlled laboratory setting using a variety of common types of physical activity. The classifier had an average sensitivity of 98.7% for physiological data collected over a range of exercise modalities and intensities in these subjects. The classifier will be added as a new module to the integrated multivariable adaptive AP system to enable the detection of aerobic and anaerobic exercise for enhancing the accuracy of insulin infusion strategies during and after exercise. PMID:26443291

  4. Physical Activities for Preschool.

    ERIC Educational Resources Information Center

    Adkins, Dorothy C.; And Others

    The underlying premise of the University of Hawaii Physical Activities for Preschool curriculum is that important contributions to a positive self-concept are made by motor independence and a realistic body image. Program objectives include: (1) the development of strength, endurance, and flexibility in skills that involve the muscles,…

  5. Shark Tagging Activities.

    ERIC Educational Resources Information Center

    Current: The Journal of Marine Education, 1998

    1998-01-01

    In this group activity, children learn about the purpose of tagging and how scientists tag a shark. Using a cut-out of a shark, students identify, measure, record data, read coordinates, and tag a shark. Includes introductory information about the purpose of tagging and the procedure, a data sheet showing original tagging data from Tampa Bay, and…

  6. Communication Systems. Laboratory Activities.

    ERIC Educational Resources Information Center

    Sutherland, Barbara, Ed.

    This communication systems guide provides teachers with learning activities for secondary students. Introductory materials include an instructional planning outline and worksheet, an outline of essential elements, a list of objectives, a course description, and a content outline. The guide contains 32 modules on the following topics: story…

  7. Activity: Computer Talk.

    ERIC Educational Resources Information Center

    Clearing: Nature and Learning in the Pacific Northwest, 1985

    1985-01-01

    Presents an activity in which students create a computer program capable of recording and projecting paper use at school. Includes instructional strategies and background information such as requirements for pounds of paper/tree, energy needs, water consumption, and paper value at the recycling center. A sample program is included. (DH)

  8. Grooming. Learning Activity Package.

    ERIC Educational Resources Information Center

    Stark, Pamela

    This learning activity package on grooming for health workers is one of a series of 12 titles developed for use in health occupations education programs. Materials in the package include objectives, a list of materials needed, information sheets, reviews (self evaluations) of portions of the content, and answers to reviews. These topics are…

  9. Dissemination Activities Report

    ERIC Educational Resources Information Center

    Barclay, Hanna; Batatia, Hudj; Bauters, Merja; Ben Ami, Zvi; Drachman, Raul; Flouris, Giorgos; Jadin, Tanja; Jalonen, Satu; Karlgren, Klas; Karpati, Andrea; Kotzinos, Dimitris; Lakkala, Minna; Lallimo, Jiri; Moen, Anne; Nygard, Kathrine; Paavola, Sami; Padiglia, Sheila; Scapolla, Marina; Sins, Patrick; Vasileva, Tania

    2008-01-01

    In the first 24 months of the project, KP-Lab members were highly dedicated to dissemination and were engaged in various dissemination activities that contributed to the prime objective of the KP-Lab dissemination efforts which is "to make the project widely known to a variety of prospective users and, at a later stage, to promote the…

  10. Engineers and Active Responsibility.

    PubMed

    Pesch, Udo

    2015-08-01

    Knowing that technologies are inherently value-laden and systemically interwoven with society, the question is how individual engineers can take up the challenge of accepting the responsibility for their work? This paper will argue that engineers have no institutional structure at the level of society that allows them to recognize, reflect upon, and actively integrate the value-laden character of their designs. Instead, engineers have to tap on the different institutional realms of market, science, and state, making their work a 'hybrid' activity combining elements from the different institutional realms. To deal with this institutional hybridity, engineers develop routines and heuristics in their professional network, which do not allow societal values to be expressed in a satisfactory manner. To allow forms of 'active' responsibility, there have to be so-called 'accountability forums' that guide moral reflections of individual actors. The paper will subsequently look at the methodologies of value-sensitive design (VSD) and constructive technology assessment (CTA) and explore whether and how these methodologies allow engineers to integrate societal values into the design technological artifacts and systems. As VSD and CTA are methodologies that look at the process of technological design, whereas the focus of this paper is on the designer, they can only be used indirectly, namely as frameworks which help to identify the contours of a framework for active responsibility of engineers.

  11. TI-73 Calculator Activities

    ERIC Educational Resources Information Center

    Phillips-Bey, Carol K.

    2004-01-01

    This article describes TI-73 calculator activities appropriate for middle school students. It was found that the use of the calculator allowed for higher-level thinking and a richer exploration of mathematical ideas by students. [Included with this article are "Dice Roll Worksheet" and "Transforming Tree Worksheet".] (Contains 9 figures.)

  12. 85 Engaging Movement Activities.

    ERIC Educational Resources Information Center

    Weikart, Phyllis S.; Carlton, Elizabeth B.

    This book presents activities to keep K-6 students moving in a variety of ways as they learn. The movement experiences are planned around key curriculum concepts in movement and music as well as in academic curriculum areas. The experiences develop students' basic timing, language abilities, vocabulary, concentration, planning skills, and…

  13. Bonus Activity Book.

    ERIC Educational Resources Information Center

    Learning, 1993

    1993-01-01

    Elementary level activity book presents suggestions for teaching students about endangered and threatened species worldwide. Students learn about what is causing the rapid extinction rate and what needs to be done. They also discover the value of rainforests and why conservationists are fighting to save them. (SM)

  14. Production Systems. Laboratory Activities.

    ERIC Educational Resources Information Center

    Gallaway, Ann, Ed.

    This production systems guide provides teachers with learning activities for secondary students. Introductory materials include an instructional planning outline and worksheet, an outline of essential elements, domains and objectives, a course description, and a content outline. The guide contains 30 modules on the following topics: production…

  15. Earthfest. Activity Book.

    ERIC Educational Resources Information Center

    Weilbacher, Mike

    1991-01-01

    An activity book to help elementary teachers and students explore the environment offers information and questions about spaceships; an ecology primer and poster with questions; information on animal adaptation with poster and questions; ecological and dramatic arts projects; a script for performance; and suggestions to make Earth Day celebrations…

  16. Antimalarial activity of cedronin.

    PubMed

    Moretti, C; Deharo, E; Sauvain, M; Jardel, C; David, P T; Gasquet, M

    1994-06-01

    Cedronin was isolated from Simaba cedron Planchon (Simaroubaceae), a species popularly believed in South America to have antimalarial properties. It was examined for in vitro and in vivo antimalarial activities and for cytotoxicity against KB cells. Experimental results showed that cedronin was active against chloroquine-sensitive and resistant strain, with an IC50 of 0.25 micrograms/ml (0.65 mumol/ml). It was also found to be active in vivo against Plasmodium vinkei with an IC50 of 1.8 mg/kg (4.7 nM/kg) in the classic 4-day test. Cedronin belongs to the small group of quassinoids with a C19 basic skeleton and shows a rather low cytotoxicity against KB cells (IC50 = 4 micrograms/ml, 10.4 microM) as compared with C20 biologically active quassinoids; however its toxic/therapeutic ratio (10/1.8) remains lower than chloroquine (10/0.5).

  17. Active rejector filter

    SciTech Connect

    Kuchinskii, A.G.; Pirogov, S.G.; Savchenko, V.M.; Yakushev, A.K.

    1985-01-01

    This paper describes an active rejector filter for suppressing noise signals in the frequency range 50-100 Hz and for extracting a vlf information signal. The filter has the following characteristics: a high input impedance, a resonant frequency of 75 Hz, a Q of 1.25, and an attenuation factor of 53 dB at resonant frequency.

  18. [Problem Solving Activities.

    ERIC Educational Resources Information Center

    Wisconsin Univ. - Stout, Menomonie. Center for Vocational, Technical and Adult Education.

    The teacher directed problem solving activities package contains 17 units: Future Community Design, Let's Build an Elevator, Let's Construct a Catapult, Let's Design a Recreational Game, Let's Make a Hand Fishing Reel, Let's Make a Wall Hanging, Let's Make a Yo-Yo, Marooned in the Past, Metrication, Mousetrap Vehicles, The Multi System…

  19. Commission 10: Solar Activity

    NASA Astrophysics Data System (ADS)

    van Driel-Gesztelyi, Lidia; Schrijver, Carolus J.; Klimchuk, James A.; Charbonneau, Paul; Fletcher, Lyndsay; Hasan, S. Sirajul; Hudson, Hugh S.; Kusano, Kanya; Mandrini, Cristina H.; Peter, Hardi; Vršnak, Bojan; Yan, Yihua

    2012-04-01

    Commission 10 of the International Astronomical Union has more than 650 members who study a wide range of activity phenomena produced by our nearest star, the Sun. Solar activity is intrinsically related to solar magnetic fields and encompasses events from the smallest energy releases (nano- or even picoflares) to the largest eruptions in the Solar System, coronal mass ejections (CMEs), which propagate into the Heliosphere reaching the Earth and beyond. Solar activity is manifested in the appearance of sunspot groups or active regions, which are the principal sources of activity phenomena from the emergence of their magnetic flux through their dispersion and decay. The period 2008-2009 saw an unanticipated extended solar cycle minimum and unprecedentedly weak polar-cap and heliospheric field. Associated with that was the 2009 historical maximum in galactic cosmic rays flux since measurements begun in the middle of the 20th Century. Since then Cycle 24 has re-started solar activity producing some spectacular eruptions observed with a fleet of spacecraft and ground-based facilities. In the last triennium major advances in our knowledge and understanding of solar activity were due to continuing success of space missions as SOHO, Hinode, RHESSI and the twin STEREO spacecraft, further enriched by the breathtaking images of the solar atmosphere produced by the Solar Dynamic Observatory (SDO) launched on 11 February 2010 in the framework of NASA's Living with a Star program. In August 2012, at the time of the IAU General Assembly in Beijing when the mandate of this Commission ends, we will be in the unique position to have for the first time a full 3-D view of the Sun and solar activity phenomena provided by the twin STEREO missions about 120 degrees behind and ahead of Earth and other spacecraft around the Earth and ground-based observatories. These new observational insights are continuously posing new questions, inspiring and advancing theoretical analysis and

  20. Interdisciplinary Astronomy Activities

    NASA Astrophysics Data System (ADS)

    Nerantzis, Nikolaos; Mitrouda, Aikaterini; Reizopoulou, Ioanna; Sidiropoulou, Eirini; Hatzidimitriou, Antonios

    2016-04-01

    On November 9th, 2015, three didactical hours were dedicated to Interdisciplinary Astronomy Activities (http://wp.me/p6Hte2-1I). Our students and their teachers formed three groups and in rotation, were engaged with the following activities: (a) viewing unique images of the Cosmos in the mobile planetarium STARLAB (http://www.planitario.gr/tholos-starlab-classic-standard.html), (b) watching the following videos: Journey to the end of the universe (https://youtu.be/Ufl_Nwbl8xs), Rosetta update (https://youtu.be/nQ9ivd7wv30), The Solar System (https://youtu.be/d66dsagrTa0), Ambition the film (https://youtu.be/H08tGjXNHO4) in the school's library. Students and teachers were informed about our solar system, the Rosetta mission, the universe, etc. and (c) tactile activities such as Meet our home and Meet our neighbors (http://astroedu.iau.org, http://nuclio.org/astroneighbours/resources) and the creation of planets' 3D models (Geology-Geography A' Class Student's book, pg.15). With the activities above we had the pleasure to join the Cosmic Light Edu Kit / International Year of Light 2015 program. After our Interdisciplinary Astronomy Activities, we did a "small" research: our students had to fill an evaluation about their educational gains and the results can be found here http://wp.me/p6Hte2-2q. Moreover, we discussed about Big Ideas of Science (http://wp.me/p3oRiZ-dm) and through the "big" impact of the Rosetta mission & the infinity of our universe, we print posters with relevant topics and place them to the classrooms. We thank Rosa Doran (Nuclio - President of the Executive Council) for her continuous assistance and support on innovative science teaching proposals. She is an inspiration.

  1. Asteroseismic stellar activity relations

    NASA Astrophysics Data System (ADS)

    Bonanno, A.; Corsaro, E.; Karoff, C.

    2014-11-01

    Context. In asteroseismology an important diagnostic of the evolutionary status of a star is the small frequency separation which is sensitive to the gradient of the mean molecular weight in the stellar interior. It is thus interesting to discuss the classical age-activity relations in terms of this quantity. Moreover, as the photospheric magnetic field tends to suppress the amplitudes of acoustic oscillations, it is important to quantify the importance of this effect by considering various activity indicators. Aims: We propose a new class of age-activity relations that connects the Mt. Wilson S index and the average scatter in the light curve with the small frequency separation and the amplitude of the p-mode oscillations. Methods: We used a Bayesian inference to compute the posterior probability of various empirical laws for a sample of 19 solar-like active stars observed by the Kepler telescope. Results: We demonstrate the presence of a clear correlation between the Mt. Wilson S index and the relative age of the stars as indicated by the small frequency separation, as well as an anti-correlation between the S index and the oscillation amplitudes. We argue that the average activity level of the stars shows a stronger correlation with the small frequency separation than with the absolute age that is often considered in the literature. Conclusions: The phenomenological laws discovered in this paper have the potential to become new important diagnostics to link stellar evolution theory with the dynamics of global magnetic fields. In particular we argue that the relation between the Mt. Wilson S index and the oscillation amplitudes is in good agreement with the findings of direct numerical simulations of magneto-convection.

  2. New immunization protocol to produce crotalic antivenom combining Crotalus durissus terrificus venom and its PLA2.

    PubMed

    Fusco, Luciano Sebastián; Rodríguez, Juan Pablo; Teibler, Pamela; Maruñak, Silvana; Acosta, Ofelia; Leiva, Laura

    2015-01-01

    Antivenoms are usually obtained by animal immunization with successive inoculations of increasing sublethal amounts of venom, which may impair the animal health. The high lethality of venom requires prolonged immunization plans with small amounts of venom. Thus, we propose an alternative plan that includes a pre-immunization of the animal with phospholipase A2, the main crotoxin component, which is responsible for the whole venom lethality. For comparison, three different immunization schemes were designed: high dose protocol (HDP; 0.5-27 mg of venom), low dose protocol (LDP; 0.1-7 mg of venom) and Mix protocol (MP; preimmunization 0.1-1.2 mg of crotalic PLA2, and then 4.5-8 mg of venom). Antibody titers were determined by ELISA, in blood plasma obtained from the marginal vein of the ear. The neutralizing ability of the different sera obtained by all protocols (HDS, LDS and MS) was tested against the most important pharmacological activities of whole venom: PLA2 activity, myotoxicity, thrombin like activity and lethality. MS showed the best neutralizing efficacy and at the same time, it was obtained by an immunization protocol that takes account of animal health care, since it requires low quantities of venoms in comparison to traditional protocols.

  3. Inhibition of sPLA2-IIA, C-reactive protein or complement: new therapy for patients with acute myocardial infarction?

    PubMed

    Krijnen, Paul A J; Meischl, Christof; Nijmeijer, Remco; Visser, Cees A; Hack, C Erik; Niessen, Hans W M

    2006-06-01

    Reperfusion of ischemic myocardium after acute myocardial infarction (AMI) induces a local activation of inflammatory reactions that results in ischemia/reperfusion (I/R)-injury. I/R-injury contributes considerably to the total cell damage in the heart after AMI. Secretory phospolipase A2-IIA (sPLA2-IIA), C-reactive protein (CRP) and complement are inflammatory mediators that have been demonstrated to play key roles in I/R injury. From studies by us and others a mechanism emerged in which sPLA2-IIA binds to reversibly damaged cardiomyocytes and subsequently induces cell death, partly by potentiating binding of CRP and subsequent complement activation. Next to this, sPLA2-IIA also has a direct toxic effect, independent of CRP or complement. Therefore, these studies indicate a crucial role of inflammatory mediators in ischemia/reperfusion injury. This review will focus on the pathogenic effects of sPLA2-IIA, CRP and complement and on the putative therapeutic effects of inhibitors of these inflammatory mediators in acute myocardial infarction.

  4. Ras activation and symmetry breaking during Dictyostelium chemotaxis.

    PubMed

    Kortholt, Arjan; Keizer-Gunnink, Ineke; Kataria, Rama; Van Haastert, Peter J M

    2013-10-01

    Central to chemotaxis is the molecular mechanism by which a shallow spatial gradient of chemoattractant induces symmetry breaking of activated signaling molecules. Previously, we have used Dictyostelium mutants to investigate the minimal requirements for chemotaxis, and identified a basal signaling module providing activation of Ras and F-actin at the leading edge. Here, we show that Ras activation after application of a pipette releasing the chemoattractant cAMP has three phases, each depending on specific guanine-nucleotide-exchange factors (GEFs). Initially a transient activation of Ras occurs at the entire cell boundary, which is proportional to the local cAMP concentrations and therefore slightly stronger at the front than in the rear of the cell. This transient Ras activation is present in gα2 (gpbB)-null cells but not in gβ (gpbA)-null cells, suggesting that Gβγ mediates the initial activation of Ras. The second phase is symmetry breaking: Ras is activated only at the side of the cell closest to the pipette. Symmetry breaking absolutely requires Gα2 and Gβγ, but not the cytoskeleton or four cAMP-induced signaling pathways, those dependent on phosphatidylinositol (3,4,5)-triphosphate [PtdIns(3,4,5)P3], cGMP, TorC2 and PLA2. As cells move in the gradient, the crescent of activated Ras in the front half of the cell becomes confined to a small area at the utmost front of the cell. Confinement of Ras activation leads to cell polarization, and depends on cGMP formation, myosin and F-actin. The experiments show that activation, symmetry breaking and confinement of Ras during Dictyostelium chemotaxis uses different G-protein subunits and a multitude of Ras GEFs and GTPase-activating proteins (GAPs).

  5. Deficiency of iPLA2β Primes Immune Cells for Proinflammation: Potential Involvement in Age-Related Mesenteric Lymph Node Lymphoma

    PubMed Central

    Inhoffen, Johannes; Tuma-Kellner, Sabine; Straub, Beate; Stremmel, Wolfgang; Chamulitrat, Walee

    2015-01-01

    Proinflammation can predispose the body to autoimmunity and cancer. We have reported that iPLA2β−/− mice are susceptible to autoimmune hepatitis and colitis. Here we determined whether cytokine release by immune cells could be affected by iPLA2β deficiency alone or combined with CD95/FasL-antibody treatment in vivo. We also determined whether cancer risk could be increased in aged mutant mice. Immune cells were isolated from 3-month old male WT and iPLA2β−/− mice, and some were injected with anti-CD95/FasL antibody for 6 h. Kupffer cells (KC) or splenocytes and liver lymphocytes were stimulated in vitro by lipopolysaccharide or concanavalinA, respectively. Whole-body iPLA2β deficiency caused increased apoptosis in liver, spleen, and mesenteric lymph node (MLN). KC from mutant mice showed suppressed release of TNFα and IL-6, while their splenocytes secreted increased levels of IFNγ and IL-17a. Upon CD95/FasL activation, the mutant KC in turn showed exaggerated cytokine release, this was accompanied by an increased release of IFNγ and IL-17a by liver lymphocytes. Aged iPLA2β−/− mice did not show follicular MLN lymphoma commonly seen in aged C57/BL6 mice. Thus, iPLA2β deficiency renders M1- and Th1/Th17-proinflammation potentially leading to a reduction in age-related MLN lymphoma during aging. PMID:26690222

  6. The Reactivation of Main-Belt Comet 324P/La Sagra (P/2010 R2)

    NASA Astrophysics Data System (ADS)

    Hsieh, Henry H.; Sheppard, Scott

    2015-11-01

    We present observations using the Baade Magellan and Canada-France-Hawaii telescopes showing that main-belt comet 324P/La Sagra, formerly known as P/2010 R2, has become active again for the first time since originally observed to be active in 2010-2011. The object appears point-source-like in March and April 2015 as it approached perihelion (true anomaly of ν~300 deg), but was ~1 mag brighter than expected if inactive, suggesting the presence of unresolved dust emission. Activity was confirmed by observations of a cometary dust tail in May and June 2015. We find an apparent net dust production rate of <0.1 kg/s during these observations. 324P is now the fourth main-belt comet confirmed to be recurrently active, a strong indication that its activity is driven by sublimation. It now has the largest confirmed active range of all likely main-belt comets, and also the most distant confirmed inbound activation point at R~2.8 AU. Further observations during the current active period will allow direct comparisons of activity strength with 324P’s 2010 activity.

  7. The reactivation of main-belt Comet 324P/La Sagra (P/2010 R2)

    NASA Astrophysics Data System (ADS)

    Hsieh, H. H.; Sheppard, S. S.

    2015-11-01

    We present observations using the Baade Magellan and Canada-France-Hawaii telescopes showing that main-belt comet 324P/La Sagra, formerly known as P/2010 R2, has become active again for the first time since originally observed to be active in 2010-2011. The object appears point-source-like in 2015 March and April as it approached perihelion (true anomaly of ν ˜ 300°), but was ˜1 mag brighter than expected if inactive, suggesting the presence of unresolved dust emission. Activity was confirmed by observations of a cometary dust tail in 2015 May and June. We find an apparent net dust production rate of {dot{M}_d}≲ 0.1 kg s-1 during these observations. 324P is now the fourth main-belt comet confirmed to be recurrently active, a strong indication that its activity is driven by sublimation. It now has the largest confirmed active range of all likely main-belt comets, and also the most distant confirmed inbound activation point at R ˜ 2.8 au. Further observations during the current active period will allow direct comparisons of activity strength with 324P's 2010 activity.

  8. Activation of satellite cells and the regeneration of human skeletal muscle are expedited by ingestion of nonsteroidal anti-inflammatory medication.

    PubMed

    Mackey, Abigail L; Rasmussen, Lotte K; Kadi, Fawzi; Schjerling, Peter; Helmark, Ida C; Ponsot, Elodie; Aagaard, Per; Durigan, João Luiz Q; Kjaer, Michael

    2016-06-01

    With this study we investigated the role of nonsteroidal anti-inflammatory drugs (NSAIDs) in human skeletal muscle regeneration. Young men ingested NSAID [1200 mg/d ibuprofen (IBU)] or placebo (PLA) daily for 2 wk before and 4 wk after an electrical stimulation-induced injury to the leg extensor muscles of one leg. Muscle biopsies were collected from the vastus lateralis muscles before and after stimulation (2.5 h and 2, 7, and 30 d) and were assessed for satellite cells and regeneration by immunohistochemistry and real-time RT-PCR, and we also measured telomere length. After injury, and compared with PLA, IBU was found to augment the proportion of ActiveNotch1(+) satellite cells at 2 d [IBU, 29 ± 3% vs. PLA, 19 ± 2% (means ± sem)], satellite cell content at 7 d [IBU, 0.16 ± 0.01 vs. PLA, 0.12 ± 0.01 (Pax7(+) cells/fiber)], and to expedite muscle repair at 30 d. The PLA group displayed a greater proportion of embryonic myosin(+) fibers and a residual ∼2-fold increase in mRNA levels of matrix proteins (all P < 0.05). Endomysial collagen was also elevated with PLA at 30 d. Minimum telomere length shortening was not observed. In conclusion, ingestion of NSAID has a potentiating effect on Notch activation of satellite cells and muscle remodeling during large-scale regeneration of injured human skeletal muscle.-Mackey, A. L., Rasmussen, L. K., Kadi, F., Schjerling, P., Helmark, I. C., Ponsot, E., Aagaard, P., Durigan, J. L. Q., Kjaer, M. Activation of satellite cells and the regeneration of human skeletal muscle are expedited by ingestion of nonsteroidal anti-inflammatory medication. PMID:26936358

  9. Lysine-tagged peptide coupling onto polylactide nanoparticles coated with activated ester-based amphiphilic copolymer: a route to highly peptide-functionalized biodegradable carriers.

    PubMed

    Handké, Nadège; Ficheux, Damien; Rollet, Marion; Delair, Thierry; Mabrouk, Kamel; Bertin, Denis; Gigmes, Didier; Verrier, Bernard; Trimaille, Thomas

    2013-03-01

    Efficient biomolecule conjugation to the surface of biodegradable colloidal carriers is crucial for their targeting efficiency in drug/vaccine delivery applications. We here propose a potent strategy to drastically improve peptide immobilization on biodegradable polylactide (PLA) nanoparticles (NPs). Our approach particularly relies on the use of an amphiphilic block copolymer PLA-b-poly(N-acryloxysuccinimide-co-N-vinylpyrrolidone) (PLA-b-P(NAS-co-NVP)) as NP surface modifier, whose the N-succinimidyl (NS) ester functions of the NAS units along the polymer chain ensure N-terminal amine peptide coupling. The well-known immunostimulatory peptide sequence derived from the human interleukin 1β (IL-1β), VQGEESNDK, was coupled on the NPs of 169 nm mean diameter in phosphate buffer (pH 8, 10 mM). A maximum amount of 2 mg immobilized per gram of NPs (i.e. 0.042 peptidenm(-2)) was obtained. Introduction of a three lysine tag at the peptide N-terminus (KKKVQGEESNDK) resulted in a dramatic improvement of the immobilized peptide amounts (27.5 mg/g NP, i.e. 0.417 peptidenm(-2)). As a comparison, the density of tagged peptide achievable on surfactant free PLA NPs of similar size (140 nm), through classical EDC or EDC/NHS activation of the surface PLA carboxylic end-groups, was found to be 6 mg/g NP (i.e. 0.075 peptidenm(-2)), showing the decisive impact of the P(NAS-co-NVP)-based hairy corona for high peptide coupling. These results demonstrate that combined use of lysine tag and PLA-b-P(NAS-co-NVP) surfactant represents a valuable platform to tune and optimize surface bio-functionalization of PLA-based biodegradable carriers.

  10. Production of natural antimicrobial compound D-phenyllactic acid using Leuconostoc mesenteroides ATCC 8293 whole cells involving highly active D-lactate dehydrogenase.

    PubMed

    Li, L; Shin, S-Y; Lee, K W; Han, N S

    2014-10-01

    Phenyllactic acid (PLA) is an antimicrobial compound naturally synthesized in various fermented foods and its D-form of PLA is known to be more active than the L-isomer. In this study, Leuconostoc mesenteroides ATCC 8293 cells, elaborating D-lactate dehydrogenase (D-ldh) were used to produce D-PLA from phenylpyruvic acid (PPA). When cultured in the presence of PPA (≤50 mmol l(-1)), growing cells produced a maximum yield of 35 mmol l(-1) of D-PLA, and the yields were between 75·2 and 83·3%. Higher conversion yields were obtained at pH 6·0-7·0 when growing cells were used, while the optimum pH range was broader for resting cells. The time required for the complete conversion of PPA into PLA could be shortened to 3 h using resting cells. D-ldh, an enzyme encoded by the LEUM_1756 gene of Leuc. mesenteroides ATCC 8293, was found to be responsible for the conversion of PPA into PLA. The Km and kcat values of the enzyme for PPA were found to be 15·4 mmol l(-1) and 5645 s(-1), respectively. The conditions required for the efficient production of D-PLA were optimized for both growing and resting cells of Leuc. mesenteroides, with special emphasis on achieving high stereoselectivity and conversion yield. Significance and impact of the study: This is the first study on the production of D-phenyllactic acid, which is a natural antimicrobial compound, from phenylpyruvate using Leuconostoc mesenteroides cells. The strain, ATCC 8293, that was used in the study, possesses high stereoselectivity and delivers a high yield. Therefore, it might be a promising candidate for use in large-scale production facilities and in fermented foods.

  11. Group IVA Cytosolic Phospholipase A2 Regulates the G2-to-M Transition by Modulating the Activity of Tumor Suppressor SIRT2

    PubMed Central

    Movahedi Naini, Said; Sheridan, Alice M.; Force, Thomas; Shah, Jagesh V.

    2015-01-01

    The G2-to-M transition (or prophase) checkpoint of the cell cycle is a critical regulator of mitotic entry. SIRT2, a tumor suppressor gene, contributes to the control of this checkpoint by blocking mitotic entry under cellular stress. However, the mechanism underlying both SIRT2 activation and regulation of the G2-to-M transition remains largely unknown. Here, we report the formation of a multiprotein complex at the G2-to-M transition in vitro and in vivo. Group IVA cytosolic phospholipase A2 (cPLA2α) acts as a bridge in this complex to promote binding of SIRT2 to cyclin A-Cdk2. Cyclin A-Cdk2 then phosphorylates SIRT2 at Ser331. This phosphorylation reduces SIRT2 catalytic activity and its binding affinity to centrosomes and mitotic spindles, promoting G2-to-M transition. We show that the inhibitory effect of cPLA2α on SIRT2 activity impacts various cellular processes, including cellular levels of histone H4 acetylated at K16 (Ac-H4K16) and Ac-α-tubulin. This regulatory effect of cPLA2α on SIRT2 defines a novel function of cPLA2α independent of its phospholipase activity and may have implications for the impact of SIRT2-related effects on tumorigenesis and age-related diseases. PMID:26303530

  12. Is Enhanced Physical Activity Possible Using Active Videogames?

    PubMed

    Baranowski, Tom; Baranowski, Janice; O'Connor, Teresia; Lu, Amy Shirong; Thompson, Debbe

    2012-06-01

    Our research indicated that 10-12-year-old children receiving two active Wii(™) (Nintendo(®); Nintendo of America, Inc., Redmond, WA) console videogames were no more physically active than children receiving two inactive videogames. Research is needed on how active videogames may increase physical activity.

  13. 101 Environmental Education Activities. Booklet 6--Social Studies Activities.

    ERIC Educational Resources Information Center

    Whitney, Helen, Comp.

    Based on the environment and directed at elementary and intermediate level students, 5 field trips are a significant part of the 12 social studies activities in the sixth booklet by the Upper Mississippi River ECO-Center outlining environmental and outdoor education activities. Most of the activities include objectives, activity description,…

  14. Is Enhanced Physical Activity Possible Using Active Videogames?

    PubMed Central

    Baranowski, Janice; O'Connor, Teresia; Lu, Amy Shirong; Thompson, Debbe

    2012-01-01

    Abstract Our research indicated that 10–12-year-old children receiving two active Wii™ (Nintendo®; Nintendo of America, Inc., Redmond, WA) console videogames were no more physically active than children receiving two inactive videogames. Research is needed on how active videogames may increase physical activity. PMID:24416640

  15. Integration of Active Video Games in Extracurricular Activity at Schools

    ERIC Educational Resources Information Center

    Lee, Jung Eun; Huang, Charles; Pope, Zachary; Gao, Zan

    2015-01-01

    Active video games require players to be physically active. Dance Dance Revolution (DDR) is an interactive dancing game that requires fast-foot movement coordinated with energetic music and visuals. The Wii and Xbox Kinect games have also become good active video games for the promotion of physical activity participation. These games are much more…

  16. Myofilament length dependent activation

    SciTech Connect

    de Tombe, Pieter P.; Mateja, Ryan D.; Tachampa, Kittipong; Mou, Younss Ait; Farman, Gerrie P.; Irving, Thomas C.

    2010-05-25

    The Frank-Starling law of the heart describes the interrelationship between end-diastolic volume and cardiac ejection volume, a regulatory system that operates on a beat-to-beat basis. The main cellular mechanism that underlies this phenomenon is an increase in the responsiveness of cardiac myofilaments to activating Ca{sup 2+} ions at a longer sarcomere length, commonly referred to as myofilament length-dependent activation. This review focuses on what molecular mechanisms may underlie myofilament length dependency. Specifically, the roles of inter-filament spacing, thick and thin filament based regulation, as well as sarcomeric regulatory proteins are discussed. Although the 'Frank-Starling law of the heart' constitutes a fundamental cardiac property that has been appreciated for well over a century, it is still not known in muscle how the contractile apparatus transduces the information concerning sarcomere length to modulate ventricular pressure development.

  17. Sulfur activation in Hiroshima

    SciTech Connect

    Kerr, G.D.; Pace, J.V. III

    1987-01-01

    In 1979, we attempted to establish the validity of source terms for the Hiroshima and Nagasaki bombs using experimental data on sulfur activation. Close agreement was observed between measured and calculated values for test firings of Nagasaki-type bombs. The calculated values were based on source terms developed by W.E. Preeg at the Los Alamos National Laboratory (LANL). A discrepancy was found, however, when we compared calculated values for the two bombs because a 1956 report by R.R. Wilson stated that sulfur acitvation by fast neutrons in Hiroshima was approximately three times greater than in Nagasaki. Our calculations based on Preeg's source-term data predicted about equal sulfur activation in the two cities.

  18. LANSCE Activity Report

    SciTech Connect

    Amy Robinson; Audrey Archuleta; Barbara Maes; Dan Strottman; Earl Hoffman; Garth Tietjen; Gene Farnum; Geoff Greene; Joyce Roberts; Ken Johnson; Paul Lewis; Roger Pynn; Stan Schriber; Steve Sterbenz; Steve Wender; Sue Harper

    1999-02-01

    The Los Alamos Neutron Science Center Activity Report describes scientific and technological progress and achievements in LANSCE Division during the period of 1995 to 1998. This report includes a message from the Division Director, an overview of LANSCE, sponsor overviews, research highlights, advanced projects and facility upgrades achievements, experimental and user program accomplishments, news and events, and a list of publications. The research highlights cover the areas of condensed-matter science and engineering, accelerator science, nuclear science, and radiography. This report also contains a compact disk that includes an overview, the Activity Report itself, LANSCE operations progress reports for 1996 and 1997, experiment reports from LANSCE users, as well as a search capability.

  19. Active microchannel heat exchanger

    DOEpatents

    Tonkovich, Anna Lee Y [Pasco, WA; Roberts, Gary L [West Richland, WA; Call, Charles J [Pasco, WA; Wegeng, Robert S [Richland, WA; Wang, Yong [Richland, WA

    2001-01-01

    The present invention is an active microchannel heat exchanger with an active heat source and with microchannel architecture. The microchannel heat exchanger has (a) an exothermic reaction chamber; (b) an exhaust chamber; and (c) a heat exchanger chamber in thermal contact with the exhaust chamber, wherein (d) heat from the exothermic reaction chamber is convected by an exothermic reaction exhaust through the exhaust chamber and by conduction through a containment wall to the working fluid in the heat exchanger chamber thereby raising a temperature of the working fluid. The invention is particularly useful as a liquid fuel vaporizer and/or a steam generator for fuel cell power systems, and as a heat source for sustaining endothermic chemical reactions and initiating exothermic reactions.

  20. Active region seismology

    NASA Technical Reports Server (NTRS)

    Bogdan, Tom; Braun, D. C.

    1995-01-01

    Active region seismology is concerned with the determination and interpretation of the interaction of the solar acoustic oscillations with near-surface target structures, such as magnetic flux concentration, sunspots, and plage. Recent observations made with a high spatial resolution and a long temporal duration enabled measurements of the scattering matrix for sunspots and solar active regions to be carried out as a function of the mode properties. Based on this information, the amount of p-mode absorption, partial-wave phase shift, and mode mixing introduced by the sunspot, could be determined. In addition, the possibility of detecting the presence of completely submerged magnetic fields was raised, and new procedures for performing acoustic holography of the solar interior are being developed. The accumulating evidence points to the mode conversion of p-modes to various magneto-atmospheric waves within the magnetic flux concentration as being the unifying physical mechanism responsible for these diverse phenomena.

  1. Finsler Active Contours

    PubMed Central

    Melonakos, John; Pichon, Eric; Angenent, Sigurd; Tannenbaum, Allen

    2009-01-01

    In this paper, we propose an image segmentation technique based on augmenting the conformal (or geodesic) active contour framework with directional information. In the isotropic case, the euclidean metric is locally multiplied by a scalar conformal factor based on image information such that the weighted length of curves lying on points of interest (typically edges) is small. The conformal factor that is chosen depends only upon position and is in this sense isotropic. Although directional information has been studied previously for other segmentation frameworks, here, we show that if one desires to add directionality in the conformal active contour framework, then one gets a well-defined minimization problem in the case that the factor defines a Finsler metric. Optimal curves may be obtained using the calculus of variations or dynamic programming-based schemes. Finally, we demonstrate the technique by extracting roads from aerial imagery, blood vessels from medical angiograms, and neural tracts from diffusion-weighted magnetic resonance imagery. PMID:18195436

  2. Active gel physics

    NASA Astrophysics Data System (ADS)

    Prost, J.; Jülicher, F.; Joanny, J.-F.

    2015-02-01

    The mechanical behaviour of cells is largely controlled by a structure that is fundamentally out of thermodynamic equilibrium: a network of crosslinked filaments subjected to the action of energy-transducing molecular motors. The study of this kind of active system was absent from conventional physics and there was a need for both new theories and new experiments. The field that has emerged in recent years to fill this gap is underpinned by a theory that takes into account the transduction of chemical energy on the molecular scale. This formalism has advanced our understanding of living systems, but it has also had an impact on research in physics per se. Here, we describe this developing field, its relevance to biology, the novelty it conveys to other areas of physics and some of the challenges in store for the future of active gel physics.

  3. Endocrine activation in tachycardias.

    PubMed

    Lukac, P; Lukacova, S; Vigas, M; Hatala, R

    2001-01-01

    This article reviews the complex character of neuroendocrine response to paroxysmal tachycardia. While the endocrine influences in arrhythmogenesis are well perceived by the cardiologists, less attention has been paid to influence of tachycardia on neuroendocrine activation. However, this may significantly alter the clinical course of tachycardias and its responses to pharmacotherapeutic interventions. Main characteristics of hormones with direct relationship to cardiovascular system (ANP, AVP, catecholamines, angiotensin and others) are listed with description of regulation of their secretion and main biological effects, especially with regard to regulation of circulation. Changes in hemodynamics during tachycardia with accompanying changes in ANP, AVP renin-angiotensin-aldosterone system, sympatho-neural and sympatho-adrenal activation are reviewed. Further research and understanding require more complex approach and concentration on interrelationship of different regulatory hormones in tachycardia. (Fig. 2, Ref. 96.) PMID:11763674

  4. Apheresis activity in Venezuela.

    PubMed

    Saltiel, Christiane

    2005-07-01

    Interest for apheresis activity has been growing in Venezuela. In 1976 there were only a few devices; in 2003, 80 apheresis machines performed 27,675 donor apheresis procedures and 547 therapeutic procedures countrywide. We report the activity at the Metropolitan Blood Bank (the largest one of the country) in the period 1999-2003: 597 therapeutic procedures were performed in 171 patients, during 212 crisis episodes. The average age was 38 +/- 16 years, 65% male and 35% female. Most of the therapeutic procedures were therapeutic plasma exchange for hematology diseases (mainly thrombotic thrombocitopenic purpura and hemophilia inhibitors), including 184 therapeutic procedures with the Autopheresis-C (Baxter Healthcare Corp., Deerfield, IL). Most common adverse effects (3.9%) were hypotension and allergic reactions to the plasma.

  5. Environmental health program activities

    NASA Technical Reports Server (NTRS)

    Bergtholdt, C. P.

    1969-01-01

    Activities reported include studies on toxic air contaminants, excessive noise, poor lighting, food sanitation, water pollution, and exposure to nonionizing radiation as health hazards. Formulations for a radiological health manual provide guidance to personnel in the procurement and safe handling of radiation producing equipment and Apollo mission planning. A literature search and development of a water analysis laboratory are outlined to obtain information regarding microbiological problems involving potable water, waste management, and personal hygiene.

  6. Ongoing Space Nuclear Activities

    NASA Technical Reports Server (NTRS)

    Houts, Michael G.

    2007-01-01

    Most ongoing US activities related to space nuclear power and propulsion are sponsored by NASA. NASA-spons0red space nuclear work is currently focused on evaluating potential fission surface power (FSP) systems and on radioisotope power systems (RPS). In addition, significant efforts related to nuclear thermal propulsion (NTP) systems have been completed and will provide a starting point for potential future NTP work.

  7. European Neutron Activation System.

    2013-01-11

    Version 03 EASY-2010 (European Activation System) consists of a wide range of codes, data and documentation all aimed at satisfying the objective of calculating the response of materials irradiated in a neutron flux. The main difference from the previous version is the upper energy limit, which has increased from 20 to 60 MeV. It is designed to investigate both fusion devices and accelerator based materials test facilities that will act as intense sources of high-energymore » neutrons causing significant activation of the surrounding materials. The very general nature of the calculational method and the data libraries means that it is applicable (with some reservations) to all situations (e.g. fission reactors or neutron sources) where materials are exposed to neutrons below 60 MeV. EASY can be divided into two parts: data and code development tools and user tools and data. The former are required to develop the latter, but EASY users only need to be able to use the inventory code FISPACT and be aware of the contents of the EAF library (the data source). The complete EASY package contains the FISPACT-2007 inventory code, the EAF-2003, EAF-2005, EAF-2007 and EAF-2010 libraries, and the EASY User Interface for the Window version. The activation package EASY-2010 is the result of significant development to extend the upper energy range from 20 to 60 MeV so that it is capable of being used for IFMIF calculations. The EAF-2010 library contains 66,256 reactions, almost five times more than in EAF-2003 (12,617). Deuteron-induced and proton-induced cross section libraries are also included, and can be used with EASY to enable calculations of the activation due to deuterons and proton [2].« less

  8. Proposed SOLCOST maintenance activities

    SciTech Connect

    1980-01-01

    This document provides a short description of work that has been accomplished to date and work in progress. A discussion of the program status as it is currently configured follows and finally proposed work by Solar Environmental Engineering Company (SEEC) in its most recently signed contract with the Department of Energy (DOE) is given. Early statements are designed to give the reader a good background so that the suggested SOLCOST maintenance activities will be more easily understood.

  9. Semiconductor active plasmonics

    NASA Astrophysics Data System (ADS)

    Mendach, Stefan; Nötzel, Richard

    2013-12-01

    Plasmonics is a research area in nanophotonics attracting increasing interest due to the potential applications in sensing and detecting, sub-wavelength confinement of light, integrated circuits, and many others. In particular, when plasmonic structures such as metal nanostructures or highly doped semiconductor particles are combined with active semiconductor materials and nanostructures, novel exciting physics and applications arise. This special section on semiconductor active plasmonics covers several of the most important and complementary directions in the field. First is the modification of the optical properties of a semiconductor nanostructure due to the close proximity of a metallic film or nanostructure. These arise from the formation hybrid plasmon/exciton states and may lead to enhanced spontaneous emission rates, directional far field emission patterns, strong coupling phenomena, and many more. Second is the realization of sub-wavelength scale nanolasers by coupling a semiconductor gain medium with a plasmonic metallic cavity. Particular emphasis is given on the major technical challenges in the fabrication of these nanolasers, such as device patterning, surface passivation, and metal deposition. While the above topics address mainly active structures and devices operating in the visible or near-infrared wavelength region, in the third, the enhanced THz extinction by periodic arrays of semiconductor particles is discussed. This is based on the build-up of surface plasmon resonances in the doped semiconductor particles which can be resonantly coupled and widely tuned by the carrier density in the semiconductor. We believe these highly diverse aspects give insight into the wide variety of new physics and applications that semiconductor active plasmonics is offering. Finally, we would like to thank the IOP editorial staff, in particular Alice Malhador, for their support, and we would also like to thank the contributors for their efforts and participation

  10. Prebiotic activation processes.

    NASA Technical Reports Server (NTRS)

    Lohrmann, R.; Orgel, L. E.

    1973-01-01

    Questions regarding the combination of amino acids and ribonucleotides to polypeptides and polynucleotides are investigated. Each of the reactions considered occurs in the solid state in plausible prebiotic conditions. Together they provide the basis for a unified scheme of amino acid and nucleotide activation. Urea, imidazole and Mg(++) are essential catalytic components of the reaction mixtures. However, these compounds could probably be replaced by other organic molecules.

  11. Active quantum plasmonics

    PubMed Central

    Marinica, Dana Codruta; Zapata, Mario; Nordlander, Peter; Kazansky, Andrey K.; M. Echenique, Pedro; Aizpurua, Javier; Borisov, Andrei G.

    2015-01-01

    The ability of localized surface plasmons to squeeze light and engineer nanoscale electromagnetic fields through electron-photon coupling at dimensions below the wavelength has turned plasmonics into a driving tool in a variety of technological applications, targeting novel and more efficient optoelectronic processes. In this context, the development of active control of plasmon excitations is a major fundamental and practical challenge. We propose a mechanism for fast and active control of the optical response of metallic nanostructures based on exploiting quantum effects in subnanometric plasmonic gaps. By applying an external dc bias across a narrow gap, a substantial change in the tunneling conductance across the junction can be induced at optical frequencies, which modifies the plasmonic resonances of the system in a reversible manner. We demonstrate the feasibility of the concept using time-dependent density functional theory calculations. Thus, along with two-dimensional structures, metal nanoparticle plasmonics can benefit from the reversibility, fast response time, and versatility of an active control strategy based on applied bias. The proposed electrical manipulation of light using quantum plasmonics establishes a new platform for many practical applications in optoelectronics. PMID:26824066

  12. THE ACTIVE ASTEROIDS

    SciTech Connect

    Jewitt, David

    2012-03-15

    Some asteroids eject dust, unexpectedly producing transient, comet-like comae and tails. First ascribed to the sublimation of near-surface water ice, mass-losing asteroids (also called 'main-belt comets') can in fact be driven by a surprising diversity of mechanisms. In this paper, we consider 11 dynamical asteroids losing mass, in nine of which the ejected material is spatially resolved. We address mechanisms for producing mass loss including rotational instability, impact ejection, electrostatic repulsion, radiation pressure sweeping, dehydration stresses, and thermal fracture, in addition to the sublimation of ice. In two objects (133P and 238P) the repetitive nature of the observed activity leaves ice sublimation as the only reasonable explanation, while in a third ((596) Scheila), a recent impact is the cause. Another impact may account for activity in P/2010 A2, but this tiny object can also be explained as having shed mass after reaching rotational instability. Mass loss from (3200) Phaethon is probably due to cracking or dehydration at extreme ({approx}1000 K) perihelion temperatures, perhaps aided by radiation pressure sweeping. For the other bodies, the mass-loss mechanisms remain unidentified, pending the acquisition of more and better data. While the active asteroid sample size remains small, the evidence for an astonishing diversity of mass-loss processes in these bodies is clear.

  13. Determining activated carbon performance

    SciTech Connect

    Naylor, W.F.; Rester, D.O.

    1995-07-01

    This article discusses the key elements involved in evaluating a system`s performance. Empty bed contact time (EBCT) is a term used to describe the length of time a liquid stream being treated is in contact with a granular activated carbon bed. The EBCT is the time required for a fluid to pass through the volume equivalent of the media bed, without the media being present. In a bed of granular activated carbon, the void volume or space between particles is usually about 45 percent. Therefore, the EBCT is about twice the true or actual time of contact between the fluid being treated and the GAC particles. The EBCT plays an important role in determining the effectiveness and longevity of granular activated carbon (GAC) used to treat liquids in a fixed-bed adsorber. Factors that influence and are influenced by EBCT, and their relationship to GAC performance in a treatment scheme include: adsorption, mass transfer zone, impurity concentration, adsorption affinity, flow rate and system design considerations.

  14. Active quantum plasmonics.

    PubMed

    Marinica, Dana Codruta; Zapata, Mario; Nordlander, Peter; Kazansky, Andrey K; M Echenique, Pedro; Aizpurua, Javier; Borisov, Andrei G

    2015-12-01

    The ability of localized surface plasmons to squeeze light and engineer nanoscale electromagnetic fields through electron-photon coupling at dimensions below the wavelength has turned plasmonics into a driving tool in a variety of technological applications, targeting novel and more efficient optoelectronic processes. In this context, the development of active control of plasmon excitations is a major fundamental and practical challenge. We propose a mechanism for fast and active control of the optical response of metallic nanostructures based on exploiting quantum effects in subnanometric plasmonic gaps. By applying an external dc bias across a narrow gap, a substantial change in the tunneling conductance across the junction can be induced at optical frequencies, which modifies the plasmonic resonances of the system in a reversible manner. We demonstrate the feasibility of the concept using time-dependent density functional theory calculations. Thus, along with two-dimensional structures, metal nanoparticle plasmonics can benefit from the reversibility, fast response time, and versatility of an active control strategy based on applied bias. The proposed electrical manipulation of light using quantum plasmonics establishes a new platform for many practical applications in optoelectronics.

  15. Cooperative nonproliferation activities

    SciTech Connect

    Ystesund, K.; Furaus, J.; Lucero, R.

    1997-08-01

    Sandia National Laboratories (SNL) under DOE sponsorship is engaged in nuclear nonproliferation activities with the Power Reactor and Nuclear Fuel Development Corporation (PNC) of Japan. From 1995 to the present SNL and PNC have been participating in a cooperative project to implement and assess the use of remote monitoring to achieve nuclear nonproliferation objectives. Implementation of remote monitoring at the PNC Joyo facility took place during 1996 and continues to date. An International Fellowship began in the Fall of 1995 and has complemented the nonproliferation study. Plans are underway to extend the Fellowship and to upgrade the existing Remote Monitoring System to include another area at the Joyo facility. SNL and PNC are currently exploring the possibility of exchanging experts with the objective of promoting regional confidence building in Northeast Asia, possibly using some of the same remote monitoring technologies. This paper will provide an overview of these activities and report on the status of cooperative nonproliferation activities being conducted by PNC and SNL.

  16. Active quantum plasmonics.

    PubMed

    Marinica, Dana Codruta; Zapata, Mario; Nordlander, Peter; Kazansky, Andrey K; M Echenique, Pedro; Aizpurua, Javier; Borisov, Andrei G

    2015-12-01

    The ability of localized surface plasmons to squeeze light and engineer nanoscale electromagnetic fields through electron-photon coupling at dimensions below the wavelength has turned plasmonics into a driving tool in a variety of technological applications, targeting novel and more efficient optoelectronic processes. In this context, the development of active control of plasmon excitations is a major fundamental and practical challenge. We propose a mechanism for fast and active control of the optical response of metallic nanostructures based on exploiting quantum effects in subnanometric plasmonic gaps. By applying an external dc bias across a narrow gap, a substantial change in the tunneling conductance across the junction can be induced at optical frequencies, which modifies the plasmonic resonances of the system in a reversible manner. We demonstrate the feasibility of the concept using time-dependent density functional theory calculations. Thus, along with two-dimensional structures, metal nanoparticle plasmonics can benefit from the reversibility, fast response time, and versatility of an active control strategy based on applied bias. The proposed electrical manipulation of light using quantum plasmonics establishes a new platform for many practical applications in optoelectronics. PMID:26824066

  17. Sesterterpenoids with Anticancer Activity

    PubMed Central

    Evidente, Antonio; Kornienko, Alexander; Lefranc, Florence; Cimmino, Alessio; Dasari, Ramesh; Evidente, Marco; Mathieu, Véronique; Kiss, Robert

    2016-01-01

    Terpenes have received a great deal of attention in the scientific literature due to complex, synthetically challenging structures and diverse biological activities associated with this class of natural products. Based on the number of C5 isoprene units they are generated from, terpenes are classified as hemi- (C5), mono- (C10), sesqui- (C15), di- (C20), sester- (C25), tri (C30), and tetraterpenes (C40). Among these, sesterterpenes and their derivatives known as sesterterpenoids, are ubiquitous secondary metabolites in fungi, marine organisms, and plants. Their structural diversity encompasses carbotricyclic ophiobolanes, polycyclic anthracenones, polycyclic furan-2-ones, polycyclic hydroquinones, among many other carbon skeletons. Furthermore, many of them possess promising biological activities including cytotoxicity and the associated potential as anticancer agents. This review discusses the natural sources that produce sesterterpenoids, provides sesterterpenoid names and their chemical structures, biological properties with the focus on anticancer activities and literature references associated with these metabolites. A critical summary of the potential of various sesterterpenoids as anticancer agents concludes the review. PMID:26295461

  18. Carbohydrate in the mouth enhances activation of brain circuitry involved in motor performance and sensory perception.

    PubMed

    Turner, Clare E; Byblow, Winston D; Stinear, Cathy M; Gant, Nicholas

    2014-09-01

    The presence of carbohydrate in the human mouth has been associated with the facilitation of motor output and improvements in physical performance. Oral receptors have been identified as a potential mode of afferent transduction for this novel form of nutrient signalling that is distinct from taste. In the current study oral exposure to carbohydrate was combined with a motor task in a neuroimaging environment to identify areas of the brain involved in this phenomenon. A mouth-rinsing protocol was conducted whilst carbohydrate (CHO) and taste-matched placebo (PLA) solutions were delivered and recovered from the mouths of 10 healthy volunteers within a double-blind, counterbalanced design. This protocol eliminates post-oral factors and controls for the perceptual qualities of solutions. Functional magnetic resonance imaging of the brain was used to identify cortical areas responsive to oral carbohydrate during rest and activity phases of a hand-grip motor task. Mean blood-oxygen-level dependent signal change experienced in the contralateral primary sensorimotor cortex was larger for CHO compared with PLA during the motor task when contrasted with a control condition. Areas of activation associated with CHO exclusively were observed over the primary taste cortex and regions involved in visual perception. Regions in the limbic system associated with reward were also significantly more active with CHO. This is the first demonstration that oral carbohydrate signalling can increase activation within the primary sensorimotor cortex during physical activity and enhance activation of neural networks involved in sensory perception.

  19. The Marine-Derived Kinase Inhibitor Fascaplysin Exerts Anti-Thrombotic Activity

    PubMed Central

    Ampofo, Emmanuel; Später, Thomas; Müller, Isabelle; Eichler, Hermann; Menger, Michael D.; Laschke, Matthias W.

    2015-01-01

    Background: The marine-derived kinase inhibitor fascaplysin down-regulates the PI3K pathway in cancer cells. Since this pathway also plays an essential role in platelet signaling, we herein investigated the effect of fascaplysin on thrombosis. Methods: Fascaplysin effects on platelet activation, platelet aggregation and platelet-leukocyte aggregates (PLA) formation were analyzed by flow cytometry. Mouse dorsal skinfold chambers were used to determine in vivo the effect of fascaplysin on photochemically induced thrombus formation and tail-vein bleeding time. Results: Pre-treatment of platelets with fascaplysin reduced the activation of glycoprotein (GP)IIb/IIIa after protease-activated receptor-1-activating peptide (PAR-1-AP), adenosine diphosphate (ADP) and phorbol-12-myristate-13-acetate (PMA) stimulation, but did not markedly affect the expression of P-selectin. This was associated with a decreased platelet aggregation. Fascaplysin also decreased PLA formation after PMA but not PAR-1-AP and ADP stimulation. This may be explained by an increased expression of CD11b on leukocytes in PAR-1-AP- and ADP-treated whole blood. In the dorsal skinfold chamber model of photochemically induced thrombus formation, fascaplysin-treated mice revealed a significantly extended complete vessel occlusion time when compared to controls. Furthermore, fascaplysin increased the tail-vein bleeding time. Conclusion: Fascaplysin exerts anti-thrombotic activity, which represents a novel mode of action in the pleiotropic activity spectrum of this compound. PMID:26569265

  20. Metabolomics reveal 1-palmitoyl lysophosphatidylcholine production by peroxisome proliferator-activated receptor α.

    PubMed

    Takahashi, Haruya; Goto, Tsuyoshi; Yamazaki, Yota; Kamakari, Kosuke; Hirata, Mariko; Suzuki, Hideyuki; Shibata, Daisuke; Nakata, Rieko; Inoue, Hiroyasu; Takahashi, Nobuyuki; Kawada, Teruo

    2015-02-01

    PPARα is well known as a master regulator of lipid metabolism. PPARα activation enhances fatty acid oxidation and decreases the levels of circulating and cellular lipids in obese diabetic patients. Although PPARα target genes are widely known, little is known about the alteration of plasma and liver metabolites during PPARα activation. Here, we report that metabolome analysis-implicated upregulation of many plasma lysoGP species during bezafibrate (PPARα agonist) treatment. In particular, 1-palmitoyl lysophosphatidylcholine [LPC(16:0)] is increased by bezafibrate treatment in both plasma and liver. In mouse primary hepatocytes, the secretion of LPC(16:0) increased on PPARα activation, and this effect was attenuated by PPARα antagonist treatment. We demonstrated that Pla2g7 gene expression levels in the murine hepatocytes were increased by PPARα activation, and the secretion of LPC(16:0) was suppressed by Pla2g7 siRNA treatment. Interestingly, LPC(16:0) activates PPARα and induces the expression of PPARα target genes in hepatocytes. Furthermore, we showed that LPC(16:0) has the ability to recover glucose uptake in adipocytes induced insulin resistance. These results reveal that LPC(16:0) is induced by PPARα activation in hepatocytes; LPC(16:0) contributes to the upregulation of PPARα target genes in hepatocytes and the recovery of glucose uptake in insulin-resistant adipocytes. PMID:25510248

  1. Multilayer Active Shell Mirrors

    NASA Astrophysics Data System (ADS)

    Steeves, John

    This thesis presents a novel active mirror technology based on carbon fiber composites and replication manufacturing processes. Multiple additional layers are implemented into the structure in order to provide the reflective layer, actuation capabilities and electrode routing. The mirror is thin, lightweight, and has large actuation capabilities. These features, along with the associated manufacturing processes, represent a significant change in design compared to traditional optics. Structural redundancy in the form of added material or support structures is replaced by thin, unsupported lightweight substrates with large actuation capabilities. Several studies motivated by the desire to improve as-manufactured figure quality are performed. Firstly, imperfections in thin CFRP laminates and their effect on post-cure shape errors are studied. Numerical models are developed and compared to experimental measurements on flat laminates. Techniques to mitigate figure errors for thicker laminates are also identified. A method of properly integrating the reflective facesheet onto the front surface of the CFRP substrate is also presented. Finally, the effect of bonding multiple initially flat active plates to the backside of a curved CFRP substrate is studied. Figure deformations along with local surface defects are predicted and characterized experimentally. By understanding the mechanics behind these processes, significant improvements to the overall figure quality have been made. Studies related to the actuation response of the mirror are also performed. The active properties of two materials are characterized and compared. Optimal active layer thicknesses for thin surface-parallel schemes are determined. Finite element simulations are used to make predictions on shape correction capabilities, demonstrating high correctabiliity and stroke over low-order modes. The effect of actuator saturation is studied and shown to significantly degrade shape correction performance. The

  2. Structural and Functional Studies of a Bothropic Myotoxin Complexed to Rosmarinic Acid: New Insights into Lys49-PLA2 Inhibition

    PubMed Central

    dos Santos, Juliana I.; Cardoso, Fábio F.; Soares, Andreimar M.; dal Pai Silva, Maeli; Gallacci, Márcia; Fontes, Marcos R. M.

    2011-01-01

    Snakebite envenoming is an important public health problem in many tropical and subtropical countries, and is considered a neglected tropical disease by the World Health Organization. Most severe cases are inflicted by species of the families Elapidae and Viperidae, and lead to a number of systemic and local effects in the victim. One of the main problems regarding viperidic accidents is prominent local tissue damage whose pathogenesis is complex and involves the combined actions of a variety of venom components. Phospholipases A2 (PLA2s) are the most abundant muscle-damaging components of these venoms. Herein, we report functional and structural studies of PrTX-I, a Lys49-PLA2 from Bothops pirajai snake venom, and the influence of rosmarinic acid (RA) upon this toxin's activities. RA is a known active component of some plant extracts and has been reported as presenting anti-myotoxic properties related to bothopic envenomation. The myotoxic activity of Lys49-PLA2s is well established in the literature and although no in vivo neurotoxicity has been observed among these toxins, in vitro neuromuscular blockade has been reported for some of these proteins. Our in vitro studies show that RA drastically reduces both the muscle damage and the neuromuscular blockade exerted by PrTX-I on mice neuromuscular preparations (by ∼80% and ∼90%, respectively). These results support the hypothesis that the two effects are closely related and lead us to suggest that they are consequences of the muscle membrane-destabilizing activity of the Lys49-PLA2. Although the C-terminal region of these proteins has been reported to comprise the myotoxic site, we demonstrate by X-ray crystallographic studies that RA interacts with PrTX-I in a different region. Consequently, a new mode of Lys49-PLA2 inhibition is proposed. Comparison of our results with others in the literature suggests possible new ways to inhibit bothropic snake venom myotoxins and improve serum therapy. PMID:22205953

  3. Changing Conceptions of Activation Energy.

    ERIC Educational Resources Information Center

    Pacey, Philip D.

    1981-01-01

    Provides background material which relates to the concept of activation energy, fundamental in the study of chemical kinetics. Compares the related concepts of the Arrhenius activation energy, the activation energy at absolute zero, the enthalpy of activation, and the threshold energy. (CS)

  4. Science Activities in Energy: Conservation.

    ERIC Educational Resources Information Center

    Oak Ridge Associated Universities, TN.

    Presented is a science activities in energy package which includes 14 activities relating to energy conservation. Activities are simple, concrete experiments for fourth, fifth and sixth grades, which illustrate principles and problems relating to energy. Each activity is outlined on a simple card which is introduced by a question. A teacher's…

  5. Metric Activities, Grades K-6.

    ERIC Educational Resources Information Center

    Draper, Bob, Comp.

    This pamphlet presents worksheets for use in fifteen activities or groups of activities designed for teaching the metric system to children in grades K through 6. The approach taken in several of the activities is one of conversion between metric and English units. The majority of the activities concern length, area, volume, and capacity. A…

  6. [Fernbank Science Center Environmental Activities].

    ERIC Educational Resources Information Center

    Shelton, Lewis

    This document is a compilation of environmental activities related directly to the environment in Georgia. A description of the physiographic characteristics of Georgia is presented upon which the activities that follow are based. These activities include soil, stream and forest investigations; meteorology activities; and plant and animal studies.…

  7. Epsiodic Activity in Radio Galaxies

    SciTech Connect

    Saikia, D.J.; Konar, C.; Jamrozy, M.; Machalski, J.; Gupta, Neeraj; Stawarz, L.; Mack, K.-H.; Siemiginowska, A.; /Harvard-Smithsonian Ctr. Astrophys.

    2007-10-15

    One of the interesting issues in our understanding of active galactic nuclei is the duration of their active phase and whether such activity is episodic. In this paper we summarize our recent results on episodic activity in radio galaxies obtained with the GMRT and the VLA.

  8. Neurotoxicity and other pharmacological activities of the snake venom phospholipase A2 OS2: The N-terminal region is more important than enzymatic activity

    PubMed Central

    Rouault, Morgane; Rash, Lachlan D.; Escoubas, Pierre; Boilard, Eric; Bollinger, James; Lomonte, Bruno; Maurin, Thomas; Guillaume, Carole; Canaan, Stéphane; Deregnaucourt, Christiane; Schrével, Joseph; Doglio, Alain; Gutiérrez, José María; Lazdunski, Michel; Gelb, Michael H.; Lambeau, Gérard

    2009-01-01

    Several snake venom secreted phospholipases A2 (sPLA2s) including OS2 exert a variety of pharmacological effects ranging from central neurotoxicity to anti-HIV activity by mechanisms that are not yet fully understood. To conclusively address the role of enzymatic activity and map the key structural elements of OS2 responsible for its pharmacological properties, we have prepared single point OS2 mutants at the catalytic site and large chimeras between OS2 and OS1, an homologous but non toxic sPLA2. Most importantly, we found that the enzymatic activity of the active site mutant H48Q is 500-fold lower than that of the wild-type protein, while central neurotoxicity is only 16-fold lower, providing convincing evidence that catalytic activity is at most a minor factor that determines central neurotoxicity. The chimera approach has identified the N-terminal region (residues 1–22) of OS2, but not the central one (residues 58–89), as crucial for both enzymatic activity and pharmacological effects. The C-terminal region of OS2 (residues 102–119) was found to be critical for enzymatic activity, but not for central neurotoxicity and anti-HIV activity, allowing us to further dissociate enzymatic activity and pharmacological effects. Finally, direct binding studies with the C-terminal chimera which poorly binds to phospholipids while it is still neurotoxic, led to the identification of a subset of brain N-type receptors which may be directly involved in central neurotoxicity. PMID:16669624

  9. The Reactivation of Main-Belt Comet 324P/La Sagra

    NASA Astrophysics Data System (ADS)

    Hsieh, H. H.

    2015-12-01

    We present observations using the Baade Magellan and Canada-France-Hawaii telescopes showing that main-belt comet 324P/La Sagra, also known as P/2010 R2, has become active again for the first time since originally observed to be active in 2010-2011. The object appears point-source-like in March and April 2015 as it approached perihelion (true anomaly of ν~300 deg), but was ~0.8-1.1 mag brighter than expected if inactive, suggesting the presence of unresolved dust emission. Activity was confirmed by observations of a cometary dust tail in May and June 2015. We find an apparent net dust production rate of M_d ~ 0.2 kg/s during these observations. 324P is now the fourth main-belt comet confirmed to be recurrently active, a strong indication that its activity is driven by sublimation. It now has the largest confirmed active range of all likely main-belt comets, and also the most distant confirmed inbound activation point at R~2.8 AU. We will also discuss the implications of the growing number of main-belt comets with confirmed recurrent activity and opportunities for confirming recurrent activity in other suspected main-belt comets.

  10. Activated human platelets induce factor XIIa-mediated contact activation.

    PubMed

    Bäck, Jennie; Sanchez, Javier; Elgue, Graciela; Ekdahl, Kristina Nilsson; Nilsson, Bo

    2010-01-01

    Earlier studies have shown that isolated platelets in buffer systems can promote activation of FXII or amplify contact activation, in the presence of a negatively charge substance or material. Still proof is lacking that FXII is activated by platelets in a more physiological environment. In this study we investigate if activated platelets can induce FXII-mediated contact activation and whether this activation affects clot formation in human blood. Human platelets were activated with a thrombin receptor-activating peptide, SFLLRN-amide, in platelet-rich plasma or in whole blood. FXIIa and FXIa in complex with preferentially antithrombin (AT) and to some extent C1-inhibitor (C1INH) were generated in response to TRAP stimulation. This contact activation was independent of surface-mediated contact activation, tissue factor pathway or thrombin. In clotting whole blood FXIIa-AT and FXIa-AT complexes were specifically formed, demonstrating that AT is a potent inhibitor of FXIIa and FXIa generated by platelet activation. Contact activation proteins were analyzed by flow cytometry and FXII, FXI, high-molecular weight kininogen, and prekallikrein were detected on activated platelets. Using chromogenic assays, enzymatic activity of platelet-associated FXIIa, FXIa, and kallikrein were demonstrated. Inhibition of FXIIa in non-anticoagulated blood also prolonged the clotting time. We conclude that platelet activation triggers FXII-mediated contact activation on the surface and in the vicinity of activated platelets. This leads specifically to generation of FXIIa-AT and FXIa-AT complexes, and contributes to clot formation. Activated platelets may thereby constitute an intravascular locus for contact activation, which may explain the recently reported importance of FXII in thrombus formation. PMID:19878657

  11. Lack of metabolic activation and predominant formation of an excreted metabolite of nontoxic platynecine-type pyrrolizidine alkaloids.

    PubMed

    Ruan, Jianqing; Liao, Cangsong; Ye, Yang; Lin, Ge

    2014-01-21

    Pyrrolizidine alkaloid (PA) poisoning is well-known because of the intake of PA-containing plant-derived natural products and PA-contaminated foodstuffs. Based on different structures of the necine bases, PAs are classified into three types: retronecine, otonecine, and platynecine type. The former two type PAs possessing an unsaturated necine base with a 1,2-double bond are hepatotoxic due to the P450-mediated metabolic activation to generate reactive pyrrolic ester, which interacts with cellular macromolecules leading to toxicity. With a saturated necine base, platynecine-type PAs are reported to be nontoxic and their nontoxicity was hypothesized to be due to the absence of metabolic activation; however, the metabolic pathway responsible for their nontoxic nature is largely unknown. In the present study, to prove the absence of metabolic activation in nontoxic platynecine-type PAs, hepatic metabolism of platyphylline (PLA), a representative platynecine-type PA, was investigated and directly compared with the representatives of two toxic types of PAs in parallel. By determining the pyrrolic ester-derived glutathione conjugate, our results confirmed that the major metabolic pathway of PLA did not lead to formation of the reactive pyrrolic ester. More interestingly, having a metabolic rate similar to that of toxic PAs, PLA also underwent oxidative metabolisms mediated by P450s, especially P450 3A4, the same enzyme that catalyzes metabolic activation of two toxic types of PAs. However, the predominant oxidative dehydrogenation pathway of PLA formed a novel metabolite, dehydroplatyphylline carboxylic acid, which was water-soluble, readily excreted, and could not interact with cellular macromolecules. In conclusion, our study confirmed that the saturated necine bases determine the absence of metabolic activation and thus govern the metabolic pathway responsible for the nontoxic nature of platynecine-type PAs. PMID:24308637

  12. Positional specificity of a phospholipase A activity induced by wounding, systemin, and oligosaccharide elicitors in tomato leaves

    PubMed Central

    Narvaez-Vasquez, J; Florin-Christensen, J; Ryan, CA

    1999-01-01

    Phospholipase A (PLA) activity, as measured by the accumulation of (14)C-lysophosphatidylcholine in leaves of tomato plants, increased rapidly and systemically in response to wounding. The increase in PLA activity in the systemic unwounded leaves was biphasic in wild-type tomato plants, peaking at 15 min and again at 60 min, but the second peak of activity was absent in transgenic prosystemin antisense plants. Supplying young excised tomato plants with the polypeptide hormone systemin also caused (14)C-lysophosphatidylcholine to increase to levels similar to those induced by wounding, but the increase in activity persisted for >2 hr. Antagonists of systemin blocked both the release of (14)C-lysophosphatidylcholine and the accumulation of defense proteins in response to systemin. (14)C-lysophosphatidylcholine levels did not increase in response to jasmonic acid. Chemical acylation of the lysophosphatidylcholine produced by wounding, systemin, and oligosaccharide elicitors followed by enzymatic hydrolysis with lipases of known specificities demostrated that the lysophosphatidylcholine is generated by a PLA with specificity for the sn-2 position. PMID:10559447

  13. The active asteroids

    NASA Astrophysics Data System (ADS)

    Jewitt, D.

    2014-07-01

    Active asteroids simultaneously possess the orbits of main-belt asteroids and the physical appearances of comets; they show transient dust comae and solar-radiation pressure-swept tails. Apart from the shear surprise at finding such strange objects in the asteroid belt, the active asteroids are scientifically interesting for several reasons. Although we are limited to scarcely more than a dozen examples, the active asteroids already reveal the distinct action of different physical processes, each previously unobserved and carrying big-picture importance for understanding the solar system. 1. IMPACT. An unambiguous asteroid-asteroid impact was observed in 2010, when a 30-m scale body struck 100-km diameter (596) Scheila. Direct observations of impacts hold scientific importance both by sampling this natural process at full scale (compared with laboratory impacts conducted at tiny scales) and because impact statistics will allow us to assess the erosion rate in the asteroid belt and the contribution of asteroid dust to the interplanetary medium. 2. CRITICAL ROTATION. Several objects have been observed in which the best explanation seems to lie with spin-up to critical periods, presumably (but not certainly) caused by YORP. Examples of both likely mass-shedding (P/2010 A2, P/2013 P5) and full break-up (P/2013 R3, shown below) exist. It has been suggested that, at sub-kilometer sizes, spin-up disruption rates may surpass impact disruption rates. Future observations will show whether or not this is true, and may ultimately lead to an improved understanding of the physics of break-up. 3. THERMAL DISINTEGRATION. Geminid parent (3200) Phaethon shows on-going mass-loss at perihelion, driven by the 1000-K surface temperatures found there. The mechanisms appear to be some combination of thermal fracture and desiccation stress. 4. SUBLIMATION. Two objects have shown repeated activity that appears to be correlated with position in the orbit. The best example is 133P, which has

  14. Advances in Activity Cliff Research.

    PubMed

    Dimova, Dilyana; Bajorath, Jürgen

    2016-05-01

    Activity cliffs, i.e. similar compounds with large potency differences, are of interest from a chemical and informatics viewpoint; as a source of structure-activity relationship information, for compound optimization, and activity prediction. Herein, recent highlights of activity cliff research are discussed including studies that have further extended our understanding of activity cliffs, yielded unprecedented insights, or paved the way for practical applications.

  15. Advances in Activity Cliff Research.

    PubMed

    Dimova, Dilyana; Bajorath, Jürgen

    2016-05-01

    Activity cliffs, i.e. similar compounds with large potency differences, are of interest from a chemical and informatics viewpoint; as a source of structure-activity relationship information, for compound optimization, and activity prediction. Herein, recent highlights of activity cliff research are discussed including studies that have further extended our understanding of activity cliffs, yielded unprecedented insights, or paved the way for practical applications. PMID:27492084

  16. Toxicity and mAChRs binding activity of Cassiopea xamachana venom from Puerto Rican coasts.

    PubMed

    Radwan, Faisal F Y; Román, Laura G; Baksi, Krishna; Burnett, Joseph W

    2005-01-01

    A separation of toxic components from the upside down jellyfish Cassiopea xamachana (Cx) was carried out to study their cytotoxic effects and examine whether these effects are combined with a binding activity to cell membrane receptors. Nematocysts containing toxins were isolated from the autolysed tentacles, ruptured by sonication, and the crude venom (CxTX) was separated from the pellets by ultracentrifugation. For identifying its bioactive components, CxTX was fractionated by gel filtration chromatography into six fractions (named fraction I-VI). The toxicity of CxTX and fractions was tested on mice; however, the hemolytic activity was tested on saline washed human erythrocytes. The LD50 of CxTX was 0.75 microg/g of mouse body and for fraction III, IV and VI were 0.28, 0.25 and 0.12 microg/g, respectively. Fractions I, II and V were not lethal at doses equivalent to LD50 1 microg/g. The hemolytic and phospholipase A2 (PLA2) activities of most fractions were well correlated with their mice toxicity. However, fraction VI, which contains the low molecular mass protein components (< or =10 kDa), has shown no PLA2 activity but highest toxicity to mice, highest hemolytic activity, and bound significantly to the acetylcholine muscarinic receptors (mAChRs) isolated from rat brain. The results suggested that fraction VI contains proteinaceous components contributing to most of cytolysis as well as membrane binding events. Meanwhile, fraction IV has shown high PLA2 that may contribute to the venom lethality and paralytic effects. PMID:15581689

  17. Metadata Activities in Biology

    SciTech Connect

    Inigo, Gil San; HUTCHISON, VIVIAN; Frame, Mike; Palanisamy, Giri

    2010-01-01

    The National Biological Information Infrastructure program has advanced the biological sciences ability to standardize, share, integrate and synthesize data by making the metadata program a core of its activities. Through strategic partnerships, a series of crosswalks for the main biological metadata specifications have enabled data providers and international clearinghouses to aggregate and disseminate tens of thousands of metadata sets describing petabytes of data records. New efforts at the National Biological Information Infrastructure are focusing on better metadata creation and curation tools, semantic mediation for data discovery and other curious initiatives.

  18. ASTP RBCC Activities

    NASA Technical Reports Server (NTRS)

    Nelson, Karl W.; McArthur, Craig; Leopard, Larry (Technical Monitor)

    2000-01-01

    This presentation reviews the activities of the Advanced Space Transportation Program (ASTP) in the development of Rocket-Based Combined Cycle (RBCC)technology. The document consist of the presentation slides for a talk scheduled to be given to the World Aviation Congress and Exhibit of SAE. Included in the review is discussion of recent accomplishments in the area of Advanced Reusable technologies (ART), which includes work in flowpath testing, and system studies of the various vehicle/engine combinations including RBCC, Turbine Based Combined Cycle (TBCC) and Pulsed Detonation Engine (PDE). Pictures of the proposed RBCC Flowpaths are included. The next steps in the development process are reviewed.

  19. GPS Activities at SLAC

    SciTech Connect

    Behrend, Dirk

    2002-11-19

    The Alignment Engineering Group of the Stanford Linear Accelerator Center (SLAC) started to use RTK (real-time kinematic) GPS equipment in order to perform structure mapping and GIS-related tasks on the SLAC campus. In a first step a continuously observing GPS station (SLAC M40) was set up. This station serves as master control station for all differential GPS activities on site and its coordinates have been determined in the well-defined global geodetic datum ITRF2000 at a given reference epoch. Some trials have been performed to test the RTK method. The tests have proven RTK to be very fast and efficient.

  20. Monitoring international nuclear activity

    SciTech Connect

    Firestone, R.B.

    2006-05-19

    The LBNL Table of Isotopes website provides primary nuclearinformation to>150,000 different users annually. We have developedthe covert technology to identify users by IP address and country todetermine the kinds of nuclear information they are retrieving. Wepropose to develop pattern recognition software to provide an earlywarning system to identify Unusual nuclear activity by country or regionSpecific nuclear/radioactive material interests We have monitored nuclearinformation for over two years and provide this information to the FBIand LLNL. Intelligence is gleaned from the website log files. Thisproposal would expand our reporting capabilities.

  1. Active terahertz metamaterials

    SciTech Connect

    Chen, Hou-tong; O' Hara, John F; Taylor, Antoinette J

    2009-01-01

    In this paper we present an overview of research in our group in terahertz (THz) metamaterials and their applications. We have developed a series of planar metamaterials operating at THz frequencies, all of which exhibit a strong resonant response. By incorporating natural materials, e.g. semiconductors, as the substrates or as critical regions of metamaterial elements, we are able to effectively control the metamaterial resonance by the application of external stimuli, e.g., photoexcitation and electrical bias. Such actively controllable metamaterials provide novel functionalities for solid-state device applications with unprecedented performance, such as THz spectroscopy, imaging, and many others.

  2. Revitalizing AIDS activism.

    PubMed

    Wolf, M

    1998-12-01

    Maxine Wolf, an activist with ACT UP New York, suggests ways to motivate others in her organization and revitalize AIDS activism. Reach out to the gay and lesbian community, get them involved in grassroots efforts, and gain their input. Participate in discussions on larger issues such as research, funding, and treatment options. Wolf also suggests becoming educated, acting in a more public way, and finding more creative ways to act. Lastly, strive for goals with high expectations that can effect change instead of merely gathering and dispensing information.

  3. Crew Activity Analyzer

    NASA Technical Reports Server (NTRS)

    Murray, James; Kirillov, Alexander

    2008-01-01

    The crew activity analyzer (CAA) is a system of electronic hardware and software for automatically identifying patterns of group activity among crew members working together in an office, cockpit, workshop, laboratory, or other enclosed space. The CAA synchronously records multiple streams of data from digital video cameras, wireless microphones, and position sensors, then plays back and processes the data to identify activity patterns specified by human analysts. The processing greatly reduces the amount of time that the analysts must spend in examining large amounts of data, enabling the analysts to concentrate on subsets of data that represent activities of interest. The CAA has potential for use in a variety of governmental and commercial applications, including planning for crews for future long space flights, designing facilities wherein humans must work in proximity for long times, improving crew training and measuring crew performance in military settings, human-factors and safety assessment, development of team procedures, and behavioral and ethnographic research. The data-acquisition hardware of the CAA (see figure) includes two video cameras: an overhead one aimed upward at a paraboloidal mirror on the ceiling and one mounted on a wall aimed in a downward slant toward the crew area. As many as four wireless microphones can be worn by crew members. The audio signals received from the microphones are digitized, then compressed in preparation for storage. Approximate locations of as many as four crew members are measured by use of a Cricket indoor location system. [The Cricket indoor location system includes ultrasonic/radio beacon and listener units. A Cricket beacon (in this case, worn by a crew member) simultaneously transmits a pulse of ultrasound and a radio signal that contains identifying information. Each Cricket listener unit measures the difference between the times of reception of the ultrasound and radio signals from an identified beacon

  4. ECLSS medical support activities

    NASA Technical Reports Server (NTRS)

    Crump, William J.; Kilgore, Melvin V., Jr.

    1991-01-01

    During the period from April 10, 1990 to April 9, 1991, the Consortium for the Space Life Sciences provided technical assistance to the NASA/MSFC water recovery efforts. This assistance was in the form of literature reviews, technical recommendations, and presentations. This final report summarizes the activities completed during this period and identifies those areas requiring additional efforts. The tasks which the University of Alabama in Huntsville (UAH) water recovery team addressed were either identified by MSFC technical representatives or chosen from those outlined in the subject statement of work.

  5. Physical Activity in Elderly.

    PubMed

    Cvecka, Jan; Tirpakova, Veronika; Sedliak, Milan; Kern, Helmut; Mayr, Winfried; Hamar, Dušan

    2015-08-24

    Aging is a multifactorial irreversible process associated with significant decline in muscle mass and neuromuscular functions. One of the most efficient methods to counteract age-related changes in muscle mass and function is physical exercise. An alternative effective intervention to improve muscle structure and performance is electrical stimulation. In the present work we present the positive effects of physical activity in elderly and a study where the effects of a 8-week period of functional electrical stimulation and strength training with proprioceptive stimulation in elderly are compared. PMID:26913164

  6. Physical Activity in Elderly

    PubMed Central

    Tirpakova, Veronika; Sedliak, Milan; Kern, Helmut; Mayr, Winfried; Hamar, Dušan

    2015-01-01

    Aging is a multifactorial irreversible process associated with significant decline in muscle mass and neuromuscular functions. One of the most efficient methods to counteract age-related changes in muscle mass and function is physical exercise. An alternative effective intervention to improve muscle structure and performance is electrical stimulation. In the present work we present the positive effects of physical activity in elderly and a study where the effects of a 8-week period of functional electrical stimulation and strength training with proprioceptive stimulation in elderly are compared. PMID:26913164

  7. Activities for the classroom

    NASA Astrophysics Data System (ADS)

    Stark, Joyce

    From my research experiences on board the R/V Atlantis, I have developed experiments that can be used in an integrated science program or for biology. These activities reflect life in extreme environments on Earth such as the hydrothermal vents and on other planets and moons in our solar system. Students can learn to map the oceans of Europa and discover how plants grow on Mars. Students have designed research projects from the experimentation that I was involved with through the REVEL program.

  8. Rationales for regulatory activity

    SciTech Connect

    Perhac, R.M.

    1997-02-01

    The author provides an outline which touches on the types of concerns about risk evaluation which are addressed in the process of establishing regulatory guides. Broadly he says regulatory activity serves three broad constituents: (1) Paternalism (private risk); (2) Promotion of social welfare (public risks); (3) Protection of individual rights (public risks). He then discusses some of the major issues encountered in reaching a decision on what is an acceptable level of risk within each of these areas, and how one establishes such a level.

  9. FY 1996 activity summary

    SciTech Connect

    1997-04-01

    The US Department of Energy Office of Nuclear and Facility Safety provides nuclear safety policy, independent technical evaluation, and technical support. A summary of these activities is provided in this report. These include: (1) changing the mission of the former production facilities to storage and waste management; (2) stabilizing nuclear materials not recycled due to production cessation or interruptions; (3) reformulating the authorization basis for existing facilities to convert to a standards based approach for operations consistent with modern expectations; and (4) implementing a modern regulatory framework for nuclear facilities. Enforcement of the Price-Anderson Amendments Act is also reported.

  10. WFIRST Project Science Activities

    NASA Technical Reports Server (NTRS)

    Gehrels, Neil

    2012-01-01

    The WFIRST Project is a joint effort between GSFC and JPL. The project scientists and engineers are working with the community Science Definition Team to define the requirements and initial design of the mission. The objective is to design an observatory that meets the WFIRST science goals of the Astr02010 Decadal Survey for minimum cost. This talk will be a report of recent project activities including requirements flowdown, detector array development, science simulations, mission costing and science outreach. Details of the interim mission design relevant to scientific capabilities will be presented.

  11. Minor meteor shower activity

    NASA Astrophysics Data System (ADS)

    Rendtel, J.

    2016-01-01

    Video meteor observations provide us with data to analyze structures in minor meteor showers or weak features in flux profiles. Samples obtained independently by other techniques allow to calibrate the data sets and to improve the confidence of results as demonstrated with a few results. Both, the confirmation of events predicted by model calculation and the input of observational data to improve the modelling results may help to better understand meteoroid stream evolution processes. Furthermore, calibrated data series can be used for studies of the long-term evolution of meteor shower activity.

  12. Enceladus: Starting Hydrothermal Activity

    NASA Technical Reports Server (NTRS)

    Matson, D. L.; Castillo-Rogez, J. C.; Johnson, T. V.; Lunine, J. I.; Davies, A. G.

    2011-01-01

    We describe a process for starting the hydrothermal activity in Enceladus' South Polar Region. The process takes advantage of fissures that reach the water table, about 1 kilometer below the surface. Filling these fissures with fresh ocean water initiates a flow of water up from an ocean that can be self-sustaining. In this hypothesis the heat to sustain the thermal anomalies and the plumes comes from a slightly warm ocean at depth. The heat is brought to the surface by water that circulates up, through the crust and then returns to the ocean.

  13. Reuse of activated alumina

    SciTech Connect

    Hobensack, J.E.

    1991-12-31

    Activated alumina is used as a trapping media to remove trace quantities of UF{sub 6} from process vent streams. The current uranium recovery method employs concentrated nitric acid which destroys the alumina pellets and forms a sludge which is a storage and disposal problem. A recently developed technique using a distilled water rinse followed by three dilute acid rinses removes on average 97% of the uranium, and leaves the pellets intact with crush strength and surface area values comparable with new material. Trapping tests confirm the effectiveness of the recycled alumina as UF{sub 6} trapping media.

  14. Neutron activation analysis system

    DOEpatents

    Taylor, M.C.; Rhodes, J.R.

    1973-12-25

    A neutron activation analysis system for monitoring a generally fluid media, such as slurries, solutions, and fluidized powders, including two separate conduit loops for circulating fluid samples within the range of radiation sources and detectors is described. Associated with the first loop is a neutron source that emits s high flux of slow and thermal neutrons. The second loop employs a fast neutron source, the flux from which is substantially free of thermal neutrons. Adjacent to both loops are gamma counters for spectrographic determination of the fluid constituents. Other gsmma sources and detectors are arranged across a portion of each loop for deterMining the fluid density. (Official Gazette)

  15. Athena: Assessment Phase Activities

    NASA Astrophysics Data System (ADS)

    Lumb, David; Ayre, Mark

    2015-09-01

    The Athena mission concept has been proposed by the community in response to science themes of the Hot and Energetic Universe. Unlike other, competitive, mission selection exercises this "Large" class observatory mission has essentially been pre-selected. Nevertheless it has to be demonstrated that Athena meets the programmatic constraints of 1Bn euro cost cap, and a readiness level appropriate for formal mission adoption by the end 2019. This should be confirmed through a Phase A study conducted with two parallel industry activities. We describe the technical and programmatic content of these and latest progress in space and ground segment definition.

  16. Bee venom phospholipase A2 ameliorates motor dysfunction and modulates microglia activation in Parkinson's disease alpha-synuclein transgenic mice.

    PubMed

    Ye, Minsook; Chung, Hwan-Suck; Lee, Chanju; Hyun Song, Joo; Shim, Insop; Kim, Youn-Sub; Bae, Hyunsu

    2016-01-01

    α-Synuclein (α-Syn) has a critical role in microglia-mediated neuroinflammation, which leads to the development of Parkinson's disease (PD). Recent studies have shown that bee venom (BV) has beneficial effects on PD symptoms in human patients or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) toxin-induced PD mice. This study investigated whether treatment with BV-derived phospholipase A2 (bvPLA2) would improve the motor dysfunction and pathological features of PD in human A53T α-Syn mutant transgenic (A53T Tg) mice. The motor dysfunction of A53T Tg mice was assessed using the pole test. The levels of α-Syn, microglia and the M1/M2 phenotype in the spinal cord were evaluated by immunofluorescence. bvPLA2 treatment significantly ameliorated motor dysfunction in A53T Tg mice. In addition, bvPLA2 significantly reduced the expression of α-Syn, the activation and numbers of microglia, and the ratio of M1/M2 in A53T Tg mice. These results suggest that bvPLA2 could be a promising treatment option for PD. PMID:27388550

  17. Characterization of Active Packaging Films Made from Poly(Lactic Acid)/Poly(Trimethylene Carbonate) Incorporated with Oregano Essential Oil.

    PubMed

    Liu, Dong; Li, Hongli; Jiang, Lin; Chuan, Yongming; Yuan, Minglong; Chen, Haiyun

    2016-01-01

    Antimicromial and antioxidant bioactive films based on poly(lactic acid)/poly(trimenthylene carbonate) films incorporated with different concentrations of oregano essential oil (OEO) were prepared by solvent casting. The antimicrobial, antioxidant, physical, thermal, microstructural, and mechanical properties of the resulting films were examined. Scanning electron microscopy analysis revealed that the cross-section of films became rougher when OEO was incorporated into PLA/PTMC blends. Differential scanning calorimetry analysis indicated that crystallinity of PLA phase decreased by the addition of OEO, but this did not affect the thermal stability of the films. Water vapor permeability of films slightly increased with increasing concentration of OEO. However, active PLA/PTMC/OEO composite films showed adequate barrier properties for food packaging application. The antimicrobial and antioxidant capacities were significantly improved with the incorporation of OEO (p < 0.05). The results demonstrated that an optimal balance between the mechanical, barrier, thermal, antioxidant, and antimicrobial properties of the films was achieved by the incorporation of 9 wt % OEO into PLA/PTMC blends. PMID:27240336

  18. Delivery of vanillin by poly(lactic-acid) nanoparticles: Development, characterization and in vitro evaluation of antioxidant activity.

    PubMed

    Dalmolin, Luciana Facco; Khalil, Najeh Maissar; Mainardes, Rubiana Mara

    2016-05-01

    Poly(lactic acid) (PLA) nanoparticles containing vanillin were prepared using an emulsion-solvent evaporation technique and were characterized and assessed for their in vitro antioxidant potential. Physicochemical properties of the nanoparticles were characterized by size, polydispersity index, zeta potential, encapsulation efficiency and stability. Solid state and thermal properties were assessed using X-ray diffraction and differential scanning calorimetry, while in vitro drug release profile was also evaluated. Results showed PLA nanoparticles having a characteristic amorphous structure, sizes in the range of 240 nm with high homogeneity in size distribution, zeta potential of -22 mV and vanillin encapsulation efficiency of 41%. In vitro release study showed a slow and sustained release of vanillin governed by diffusion. Nanoparticles were stable over a period of three months. Antioxidant ability of the vanillin-loaded PLA nanoparticles in scavenging the radical 2,2-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) was inferior to free vanillin and due to its prolonged release showed a profile that was both time and concentration dependent, while free vanillin showed concentration-dependent activity. The study concluded that PLA nanoparticles are potential carriers for vanillin delivery. PMID:26952391

  19. Characterization of Active Packaging Films Made from Poly(Lactic Acid)/Poly(Trimethylene Carbonate) Incorporated with Oregano Essential Oil.

    PubMed

    Liu, Dong; Li, Hongli; Jiang, Lin; Chuan, Yongming; Yuan, Minglong; Chen, Haiyun

    2016-01-01

    Antimicromial and antioxidant bioactive films based on poly(lactic acid)/poly(trimenthylene carbonate) films incorporated with different concentrations of oregano essential oil (OEO) were prepared by solvent casting. The antimicrobial, antioxidant, physical, thermal, microstructural, and mechanical properties of the resulting films were examined. Scanning electron microscopy analysis revealed that the cross-section of films became rougher when OEO was incorporated into PLA/PTMC blends. Differential scanning calorimetry analysis indicated that crystallinity of PLA phase decreased by the addition of OEO, but this did not affect the thermal stability of the films. Water vapor permeability of films slightly increased with increasing concentration of OEO. However, active PLA/PTMC/OEO composite films showed adequate barrier properties for food packaging application. The antimicrobial and antioxidant capacities were significantly improved with the incorporation of OEO (p < 0.05). The results demonstrated that an optimal balance between the mechanical, barrier, thermal, antioxidant, and antimicrobial properties of the films was achieved by the incorporation of 9 wt % OEO into PLA/PTMC blends.

  20. Bee venom phospholipase A2 ameliorates motor dysfunction and modulates microglia activation in Parkinson's disease alpha-synuclein transgenic mice

    PubMed Central

    Ye, Minsook; Chung, Hwan-Suck; Lee, Chanju; Hyun Song, Joo; Shim, Insop; Kim, Youn-Sub; Bae, Hyunsu

    2016-01-01

    α-Synuclein (α-Syn) has a critical role in microglia-mediated neuroinflammation, which leads to the development of Parkinson's disease (PD). Recent studies have shown that bee venom (BV) has beneficial effects on PD symptoms in human patients or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) toxin-induced PD mice. This study investigated whether treatment with BV-derived phospholipase A2 (bvPLA2) would improve the motor dysfunction and pathological features of PD in human A53T α-Syn mutant transgenic (A53T Tg) mice. The motor dysfunction of A53T Tg mice was assessed using the pole test. The levels of α-Syn, microglia and the M1/M2 phenotype in the spinal cord were evaluated by immunofluorescence. bvPLA2 treatment significantly ameliorated motor dysfunction in A53T Tg mice. In addition, bvPLA2 significantly reduced the expression of α-Syn, the activation and numbers of microglia, and the ratio of M1/M2 in A53T Tg mice. These results suggest that bvPLA2 could be a promising treatment option for PD. PMID:27388550

  1. Delivery of vanillin by poly(lactic-acid) nanoparticles: Development, characterization and in vitro evaluation of antioxidant activity.

    PubMed

    Dalmolin, Luciana Facco; Khalil, Najeh Maissar; Mainardes, Rubiana Mara

    2016-05-01

    Poly(lactic acid) (PLA) nanoparticles containing vanillin were prepared using an emulsion-solvent evaporation technique and were characterized and assessed for their in vitro antioxidant potential. Physicochemical properties of the nanoparticles were characterized by size, polydispersity index, zeta potential, encapsulation efficiency and stability. Solid state and thermal properties were assessed using X-ray diffraction and differential scanning calorimetry, while in vitro drug release profile was also evaluated. Results showed PLA nanoparticles having a characteristic amorphous structure, sizes in the range of 240 nm with high homogeneity in size distribution, zeta potential of -22 mV and vanillin encapsulation efficiency of 41%. In vitro release study showed a slow and sustained release of vanillin governed by diffusion. Nanoparticles were stable over a period of three months. Antioxidant ability of the vanillin-loaded PLA nanoparticles in scavenging the radical 2,2-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) was inferior to free vanillin and due to its prolonged release showed a profile that was both time and concentration dependent, while free vanillin showed concentration-dependent activity. The study concluded that PLA nanoparticles are potential carriers for vanillin delivery.

  2. Active travel intervention and physical activity behaviour: an evaluation.

    PubMed

    Norwood, Patricia; Eberth, Barbara; Farrar, Shelley; Anable, Jillian; Ludbrook, Anne

    2014-07-01

    A physically active lifestyle is an important contributor to individual health and well-being. The evidence linking higher physical activity levels with better levels of morbidity and mortality is well understood. Despite this, physical inactivity remains a major global risk factor for mortality and, consequently, encouraging individuals to pursue physically active lifestyles has been an integral part of public health policy in many countries. Physical activity promotion and interventions are now firmly on national health policy agendas, including policies that promote active travel such as walking and cycling. This study evaluates one such active travel initiative, the Smarter Choices, Smarter Places programme in Scotland, intended to encourage uptake of walking, cycling and the use of public transport as more active forms of travel. House to house surveys were conducted before and after the programme intervention, in May/June 2009 and 2012 (12,411 surveys in 2009 and 9542 in 2012), for the evaluation of the programme. This paper analyses the physical activity data collected, focussing on what can be inferred from the initiative with regards to adult uptake of physical activity participation and whether, for those who participated in physical activity, the initiative impacted on meeting recommended physical activity guidelines. The results suggest that the initiative impacted positively on the likelihood of physical activity participation and meeting the recommended physical activity guidelines. Individuals in the intervention areas were on average 6% more likely to meet the physical activity guidelines compared to individuals in the non intervention areas. However, the absolute prevalence of physical activity participation declined in both intervention and control areas over time. Our evaluation of this active transport initiative indicates that similar programmes may aid in contributing to achieving physical activity targets and adds to the international

  3. Active travel intervention and physical activity behaviour: an evaluation.

    PubMed

    Norwood, Patricia; Eberth, Barbara; Farrar, Shelley; Anable, Jillian; Ludbrook, Anne

    2014-07-01

    A physically active lifestyle is an important contributor to individual health and well-being. The evidence linking higher physical activity levels with better levels of morbidity and mortality is well understood. Despite this, physical inactivity remains a major global risk factor for mortality and, consequently, encouraging individuals to pursue physically active lifestyles has been an integral part of public health policy in many countries. Physical activity promotion and interventions are now firmly on national health policy agendas, including policies that promote active travel such as walking and cycling. This study evaluates one such active travel initiative, the Smarter Choices, Smarter Places programme in Scotland, intended to encourage uptake of walking, cycling and the use of public transport as more active forms of travel. House to house surveys were conducted before and after the programme intervention, in May/June 2009 and 2012 (12,411 surveys in 2009 and 9542 in 2012), for the evaluation of the programme. This paper analyses the physical activity data collected, focussing on what can be inferred from the initiative with regards to adult uptake of physical activity participation and whether, for those who participated in physical activity, the initiative impacted on meeting recommended physical activity guidelines. The results suggest that the initiative impacted positively on the likelihood of physical activity participation and meeting the recommended physical activity guidelines. Individuals in the intervention areas were on average 6% more likely to meet the physical activity guidelines compared to individuals in the non intervention areas. However, the absolute prevalence of physical activity participation declined in both intervention and control areas over time. Our evaluation of this active transport initiative indicates that similar programmes may aid in contributing to achieving physical activity targets and adds to the international

  4. Clonorchis sinensis lysophospholipase inhibits TGF-β1-induced expression of pro-fibrogenic genes through attenuating the activations of Smad3, JNK2, and ERK1/2 in hepatic stellate cell line LX-2.

    PubMed

    Zhou, Lina; Shang, Mei; Shi, Mengchen; Zhao, Lu; Lin, Zhipeng; Chen, Tingjin; Wu, Yinjuan; Tang, Zeli; Sun, Hengchang; Yu, Jinyun; Huang, Yan; Yu, Xinbing

    2016-02-01

    Liver fibrosis is a wound healing response associated with chronic liver injury. Hepatic stellate cells (HSCs) activation is a key event in the development of liver fibrosis. Since helminths have the ability to live for decades in the host by establishing an adaptive relationship in the interplay with its hosts, we hypothesize that whether Clonochis sinensis LysophospholipaseA (CsLysoPLA), a component of excretory/secretory proteins, can attenuate the fibrogenic response by inhibiting activation of LX-2 cells, thereby balancing the pro-fibrotic and anti-fibrotic response during the Clonochis sinensis (C. sinensis) infection. In the present study, LX-2 cells were stimulated with CsLysoPLA in the presence of TGF-β1, and the expressions of collagen type I (COL1A1), α-smooth muscle actin (α-SMA), and matrix metalloproteinase 2 (MMP2) were decreased. In addition, CsLysoPLA significantly inhibited the proliferation and migration of LX-2 cells stimulated by TGF-β1. Pretreatment of LX-2 cells with CsLysoPLA attenuated the phosphorylation of Smad3 as well as JNK2 and ERK1/2 in response to the stimulation of TGF-β1. For the first time, our results showed an anti-fibrogenic effect of CsLysoPLA by attenuating the response of LX-2 cells to TGF-β1 through inhibiting the activations of Smad3, ERK1/2, and JNK2. PMID:26486942

  5. Novel procedure to enhance PLA surface properties by chitosan irreversible immobilization

    NASA Astrophysics Data System (ADS)

    Stoleru, Elena; Dumitriu, Raluca Petronela; Munteanu, Bogdanel Silvestru; Zaharescu, Traian; Tănase, Elisabeta Elena; Mitelut, Amalia; Ailiesei, Gabriela-Liliana; Vasile, Cornelia

    2016-03-01

    A novel two step procedure was applied for poly(lactic acid) (PLA) functionalization consisting in the exposure to cold radiofrequency plasma in nitrogen atmosphere or to gamma irradiation followed by "grafting to" of a chitosan layer using carbodiimide chemistry. The adhesion and stability of the deposited surface layer was assured by plasma/gamma irradiation treatment while the chitosan layer offers antifungal/antibacterial/antioxidant activities. Chitosan with different viscosities/deacetylation degree was deposited by electrospinning or immersion methods. Correlations between rheological behavior of chitosan solutions and chitosan layer deposition conditions are made. The PLA surface properties were investigated by water contact angle measurements, ATR-FTIR spectroscopy, AFM, chemiluminiscence, etc. It has been established that the surface roughness increases direct proportional with cold plasma duration and gamma irradiation dose and further increases by chitosan coating which at its turn depends on chitosan characteristics (viscosity and deacetylation degree) and method of deposition. Nano-fibers with relatively homogeneous and reproducible features are obtained by electrospinning of highly viscous chitosan while with the other two types of chitosan both microparticles and nano-fibers are formed. The chitosan coating obtained by immersion is more homogenous and compact and has a better antibacterial activity than the electrospun layer as fiber meshes.

  6. Effect of surface fluorination of TiO2 particles on photocatalitytic activity of a hybrid multilayer coating obtained by sol-gel method.

    PubMed

    Zhu, Yunfeng; Piscitelli, Filomena; Buonocore, Giovanna G; Lavorgna, Marino; Amendola, Eugenio; Ambrosio, Luigi

    2012-01-01

    A multilayer photoactive coating containing surface fluorinated TiO(2) nanoparticles and hybrid matrices by sol gel approach based on renewable chitosan was applied on poly(lactic acid) (PLA) film by a step wise spin-coating method. The upper photoactive layer contains nano-sized functionalized TiO(2) particles dispersed in a siloxane based matrix. For the purpose of improving TiO(2) dispersion at the air interface coating surface, TiO(2) nanoparticles were modified by silane coupling agent 1H,1H,2H,2H-perfluorooctyltriethoxysilane (FTS) with fluoro-organic side chains. An additional hybrid material consisting of chitosan (CS) cross-linked with 3-glycidyloxypropyl trimethoxy silane (GOTMS) was applied as interlayer between the PLA substrate and the upper photoactive coating to increase the adhesion and reciprocal affinity. The multilayer TiO(2)/CS-GOTMS coatings on PLA films showed a thickness of ~4-6 μm and resulted highly transparent. Their structure was exhaustively characterized by SEM, optical microscope, UV-vis spectroscopy and contact angle measurements. The photocatalytic activity of the multilayer coatings were investigated using methyl orange (MeO) as a target pollutant; the results showed that PLA films coated with surface fluorinated particles exhibit higher activity than films with neat particles, because of a better dispersion of TiO(2) particles. The mechanical properties of PLA and films coated with fluorinated particles, irradiated by UV light were also investigated; the results showed that the degradation of PLA substrate was markedly suppressed because of the UV adsorptive action of the multilayer coating. PMID:22117597

  7. Tracking dynamic team activity

    SciTech Connect

    Tambe, M.

    1996-12-31

    AI researchers are striving to build complex multi-agent worlds with intended applications ranging from the RoboCup robotic soccer tournaments, to interactive virtual theatre, to large-scale real-world battlefield simulations. Agent tracking - monitoring other agent`s actions and inferring their higher-level goals and intentions - is a central requirement in such worlds. While previous work has mostly focused on tracking individual agents, this paper goes beyond by focusing on agent teams. Team tracking poses the challenge of tracking a team`s joint goals and plans. Dynamic, real-time environments add to the challenge, as ambiguities have to be resolved in real-time. The central hypothesis underlying the present work is that an explicit team-oriented perspective enables effective team tracking. This hypothesis is instantiated using the model tracing technology employed in tracking individual agents. Thus, to track team activities, team models are put to service. Team models are a concrete application of the joint intentions framework and enable an agent to track team activities, regardless of the agent`s being a collaborative participant or a non-participant in the team. To facilitate real-time ambiguity resolution with team models: (i) aspects of tracking are cast as constraint satisfaction problems to exploit constraint propagation techniques; and (ii) a cost minimality criterion is applied to constrain tracking search. Empirical results from two separate tasks in real-world, dynamic environments one collaborative and one competitive - are provided.

  8. Activating Event Knowledge

    PubMed Central

    Hare, Mary; Jones, Michael; Thomson, Caroline; Kelly, Sarah; McRae, Ken

    2009-01-01

    An increasing number of results in sentence and discourse processing demonstrate that comprehension relies on rich pragmatic knowledge about real-world events, and that incoming words incrementally activate such knowledge. If so, then even outside of any larger context, nouns should activate knowledge of the generalized events that they denote or typically play a role in. We used short stimulus onset asynchrony priming to demonstrate that (1) event nouns prime people (sale-shopper) and objects (trip-luggage) commonly found at those events; (2) location nouns prime people/animals (hospital-doctor) and objects (barn-hay) commonly found at those locations; and (3) instrument nouns prime things on which those instruments are commonly used (key-door), but not the types of people who tend to use them (hose-gardener). The priming effects are not due to normative word association. On our account, facilitation results from event knowledge relating primes and targets. This has much in common with computational models like LSA or BEAGLE in which one word primes another if they frequently occur in similar contexts. LSA predicts priming for all six experiments, whereas BEAGLE correctly predicted that priming should not occur for the instrument-people relation but should occur for the other five. We conclude that event-based relations are encoded in semantic memory and computed as part of word meaning, and have a strong influence on language comprehension. PMID:19298961

  9. The Active Solid Earth

    NASA Astrophysics Data System (ADS)

    Ebinger, Cynthia

    2016-04-01

    Dynamic processes in Earth's crust, mantle and core shape Earth's surface and magnetic field over time scales of seconds to millennia, and even longer time scales as recorded in the ca. 4 Ga rock record. Our focus is the earthquake-volcano deformation cycles that occur over human time scales, and their comparison with time-averaged deformation studies, with emphasis on mantle plume provinces where magma and volatile release and vertical tectonics are readily detectable. Active deformation processes at continental and oceanic rift and back arc zones provide critical constraints on mantle dynamics, the role of fluids (volatiles, magma, water), and plate rheology. For example, recent studies of the East African rift zone, which formed above one of Earth's largest mantle upwellings reveal that magma production and volatile release rates are comparable to those of magmatic arcs, the archetypal zones of continental crustal creation. Finite-length faults achieve some plate deformation, but magma intrusion in the form of dikes accommodates extension in continental, back-arc, and oceanic rifts, and intrusion as sills causes permanent uplift that modulates the local time-space scales of earthquakes and volcanoes. Volatile release from magma intrusion may reduce fault friction and permeability, facilitating aseismic slip and creating magma pathways. We explore the implications of active deformation studies to models of the time-averaged structure of plume and extensional provinces in continental and oceanic plate settings.

  10. Active Astronomy Roadshow Haiti

    NASA Astrophysics Data System (ADS)

    Laycock, Silas; Oram, Kathleen; Alabre, Dayana; Douyon, Ralph; UMass Lowell Haiti Development Studies Center

    2016-01-01

    College-age Haitian students working with advisors and volunteers from UMass Lowell in 2015 developed and tested an activity-based K-8 curriculum in astronomy, space, and earth science. Our partner school is located in Les Cayes, Haiti a city where only 65% of children attend school, and only half of those will complete 6th grade. Astronomy provides an accessible and non-intimidating entry into science, and activity-based learning contrasts with the predominant traditional teaching techniques in use in Haiti, to reach and inspire a different cohort of learners. Teachers are predominantly women in Haiti, so part of the effort involves connecting them with scientists, engineers and teacher peers in the US. As a developing nation, it is vital for Haitian (as for all) children to grow up viewing women as leaders in science. Meanwhile in the US, few are aware of the reality of getting an education in a 3rd world nation (i.e. most of the world), so we also joined with teachers in Massachusetts to give US school children a peek at what daily life is like for their peers living in our vibrant but impoverished neighbor. Our Haitian partners are committed to helping their sister-schools with curriculum and educator workshops, so that the overall quality of education can rise, and not be limited to the very few schools with access to resources. We will describe the activites, motivation, and and the lessons learned from our first year of the project.

  11. Active Near Earth Asteroids

    NASA Astrophysics Data System (ADS)

    Jenniskens, Peter

    2015-08-01

    Past activity from Near Earth Asteroids is recorded in the meteoroid streams that cause our meteor showers. Automated meteoroid orbit surveys by photographic, low-light video, specular radar, and head-echo radar reflections are providing the first maps of meteor shower activity at different particle sizes. There are distinct differences in particle size distributions among streams. The underlaying mechanisms that created these streams are illuminated: fragmentation from spin-up or thermal stresses, meteoroid ejection by water vapor drag, and ejection of icy particles by CO and CO2 sublimation. The distribution of the meteoroid orbital elements probe the subsequent evolution by planetary perturbations and sample the range of dynamical processes to which Near Earth Asteroids are exposed. The non-stream "sporadic" meteors probe early stages in the evolution from meteoroid streams into the zodiacal dust cloud. We see that the lifetime of large meteoroids is generally not limited by collisions. Results obtained by the CAMS video survey of meteoroid orbits are compared to those from other orbit surveys. Since October 2010, over 200,000 meteoroid orbits have been measured. First results from an expansion into the southern hemisphere are also presented, as are first results from the measurement of main element compositions. Among the many streams detected so far, the Geminid and Sextantid showers stand out by having a relatively high particle density and derive from parent bodies that appear to have originated in the main belt.

  12. Neutron activation for ITER

    SciTech Connect

    Barnes, C.W.; Loughlin, M.J.; Nishitani, Takeo

    1996-04-29

    There are three primary goals for the Neutron Activation system for ITER: maintain a robust relative measure of fusion power with stability and high dynamic range (7 orders of magnitude); allow an absolute calibration of fusion power (energy); and provide a flexible and reliable system for materials testing. The nature of the activation technique is such that stability and high dynamic range can be intrinsic properties of the system. It has also been the technique that demonstrated (on JET and TFTR) the highest accuracy neutron measurements in DT operation. Since the gamma-ray detectors are not located on the tokamak and are therefore amenable to accurate characterization, and if material foils are placed very close to the ITER plasma with minimum scattering or attenuation, high overall accuracy in the fusion energy production (7--10%) should be achievable on ITER. In the paper, a conceptual design is presented. A system is shown to be capable of meeting these three goals, also detailed design issues remain to be solved.

  13. Active frequency selective surfaces

    NASA Astrophysics Data System (ADS)

    Buchwald, Walter R.; Hendrickson, Joshua; Cleary, Justin W.; Guo, Junpeng

    2013-05-01

    Split ring resonator arrays are investigated for use as active elements for the realization of voltage controllable frequency selective surfaces. Finite difference time domain simulations suggest the absorptive and reflective properties of such surfaces can be externally controlled through modifications of the split ring resonator gap impedance. In this work, such voltage-controlled resonance tuning is obtained through the addition of an appropriately designed high electron mobility transistor positioned across the split ring resonator gap. It is shown that a 0.5μm gate length high electron mobility transistor allows voltage controllable switching between the two resonant conditions associated with a split ring resonator and that of a closed loop geometry when the surface is illuminated with THz radiation. Partial switching between these two resonant conditions is observed at larger gate lengths. Such active frequency selective surfaces are proposed, for example, for use as modulators in THz detection schemes and as RF filters in radar applications when scaled to operate at GHz frequencies.

  14. Active Chiral Plasmonics.

    PubMed

    Yin, Xinghui; Schäferling, Martin; Michel, Ann-Katrin U; Tittl, Andreas; Wuttig, Matthias; Taubner, Thomas; Giessen, Harald

    2015-07-01

    Active control over the handedness of a chiral metamaterial has the potential to serve as key element for highly integrated polarization engineering approaches, polarization sensitive imaging devices, and stereo display technologies. However, this is hard to achieve as it seemingly involves the reconfiguration of the metamolecule from a left-handed into a right-handed enantiomer and vice versa. This type of mechanical actuation is intricate and usually neither monolithically realizable nor viable for high-speed applications. Here, enabled by the phase change material Ge3Sb2Te6 (GST-326), we demonstrate a tunable and switchable mid-infrared plasmonic chiral metamaterial in a proof-of-concept experiment. A large tunability range of the circular dichroism response from λ = 4.15 to 4.90 μm is achieved, and we experimentally demonstrate that the combination of a passive bias-type chiral layer with the active chiral metamaterial allows for switchable chirality, that is, the reversal of the circular dichroism sign, in a fully planar, layered design without the need for geometrical reconfiguration. Because phase change materials can be electrically and optically switched, our designs may open up a path for highly integrated mid-IR polarization engineering devices that can be modulated on ultrafast time scales.

  15. Regulation of inflammasome activation

    PubMed Central

    Man, Si Ming; Kanneganti, Thirumala-Devi

    2015-01-01

    Summary Inflammasome biology is one of the most exciting and rapidly growing areas in immunology. Over the past 10 years, inflammasomes have been recognized for their roles in the host defense against invading pathogens and in the development of cancer, autoinflammatory, metabolic, and neurodegenerative diseases. Assembly of an inflammasome complex requires cytosolic sensing of pathogen-associated molecular patterns or danger-associated molecular patterns by a nucleotide-binding domain and leucine-rich repeat receptor (NLR) or absent in melanoma 2-like receptor (ALR). NLRs and ALRs engage caspase-1, in most cases requiring the adapter protein apoptosis-associated speck-like protein containing a CARD (ASC), to catalyze proteolytic cleavage of pro-interleukin-1β (pro-IL-1β) and pro-IL-18 and drive pyroptosis. Recent studies indicate that caspase-8, caspase-11, IL-1R–associated kinases (IRAK), and receptor-interacting protein (RIP) kinases contribute to inflammasome functions. In addition, post-translational modifications, including ubiquitination, deubiquitination, phosphorylation, and degradation, control almost every aspect of inflammasome activities. Genetic studies indicate that mutations in NLRP1, NLRP3, NLRC4, and AIM2 are linked to the development of autoinflammatory diseases, enterocolitis, and cancer. Overall, these findings transform our understanding of the basic biology and clinical relevance of inflammasomes. In this review, we provide an overview of the latest development of inflammasome research and discuss how inflammasome activities govern health and disease. PMID:25879280

  16. Harmonic active contours.

    PubMed

    Estellers, Virginia; Zosso, Dominique; Bresson, Xavier; Thiran, Jean-Philippe

    2014-01-01

    We propose a segmentation method based on the geometric representation of images as 2-D manifolds embedded in a higher dimensional space. The segmentation is formulated as a minimization problem, where the contours are described by a level set function and the objective functional corresponds to the surface of the image manifold. In this geometric framework, both data-fidelity and regularity terms of the segmentation are represented by a single functional that intrinsically aligns the gradients of the level set function with the gradients of the image and results in a segmentation criterion that exploits the directional information of image gradients to overcome image inhomogeneities and fragmented contours. The proposed formulation combines this robust alignment of gradients with attractive properties of previous methods developed in the same geometric framework: 1) the natural coupling of image channels proposed for anisotropic diffusion and 2) the ability of subjective surfaces to detect weak edges and close fragmented boundaries. The potential of such a geometric approach lies in the general definition of Riemannian manifolds, which naturally generalizes existing segmentation methods (the geodesic active contours, the active contours without edges, and the robust edge integrator) to higher dimensional spaces, non-flat images, and feature spaces. Our experiments show that the proposed technique improves the segmentation of multi-channel images, images subject to inhomogeneities, and images characterized by geometric structures like ridges or valleys.

  17. Active Wollaston polarimetry

    NASA Astrophysics Data System (ADS)

    Neal, R. M.; Dayton, David; Gonglewski, John

    2005-10-01

    Active imaging polarimetry is a unique imaging technique in which a particular scene of interest is illuminated by a laser source with a known polarization state. Changes in the state of polarization of the received light yields information beyond what is available in conventional intensity imaging. This approach has an advantage over passive polarimetry in that one has control over the polarization state of the illumination with the potential of determining all sixteen elements of the associated Mueller matrix. While determining the entire Mueller matrix is the most comprehensive method for describing the polarization changing properties of the scene, for most cases it does not yield significantly more information than simply determining the 4 diagonal elements of the Mueller matrix. The Active Wollaston Polarimeter is based around the ability of the Wollaston prism to split orthogonal polarization states into two beams propagating at slightly different angles allowing two images to be formed on a single camera. The Wollaston prism, combined with a series of liquid crystal variable retarders allows monopulse determination of any polarization contrast image (PCI), which is directly related to a specific Muller matrix element. This technique results in a fast, compact polarization measurement system. This paper presents the continued investigation and analysis of the performance of the polarimeter and possible viability as a practical polarization measurement system.

  18. Chitosan-induced phospholipase A2 activation and arachidonic acid mobilization in P388D1 macrophages.

    PubMed

    Bianco, I D; Balsinde, J; Beltramo, D M; Castagna, L F; Landa, C A; Dennis, E A

    2000-01-28

    We have found that chitosan, a polysaccharide present in fungal cell walls, is able to activate macrophages for enhanced mobilization of arachidonic acid in a dose- and time-dependent manner. Studies aimed at identifying the intracellular effector(s) implicated in chitosan-induced arachidonate release revealed the involvement of the cytosolic Group IV phospholipase A2 (PLA2), as judged by the inhibitory effect of methyl arachidonoyl fluorophosphonate but not of bromoenol lactone. Interestingly, priming of the macrophages with lipopolysaccharide renders the cells more sensitive to a subsequent stimulation with chitosan, and this enhancement is totally blocked by the secretory PLA2 inhibitor 3-(3-acetamide)-1-benzyl-2-ethylindolyl-5-oxy-propanesulfonic acid (LY311727). Collectively, the results of this work establish chitosan as a novel macrophage-activating factor that elicits AA mobilization in P388D1 macrophages by a mechanism involving the participation of two distinct phospholipases A2. PMID:10682846

  19. Mechanical stimulation of skeletal muscle generates lipid-related second messengers by phospholipase activation

    NASA Technical Reports Server (NTRS)

    Vandenburgh, H. H.; Shansky, J.; Karlisch, P.; Solerssi, R. L.

    1993-01-01

    Repetitive mechanical stimulation of cultured avian skeletal muscle increases the synthesis of prostaglandins (PG) E2 and F2 alpha which regulate protein turnover rates and muscle cell growth. These stretch-induced PG increases are reduced in low extracellular calcium medium and by specific phospholipase inhibitors. Mechanical stimulation increases the breakdown rate of 3H-arachidonic acid labelled phospholipids, releasing free 3H-arachidonic acid, the rate-limiting precursor of PG synthesis. Mechanical stimulation also increases 3H-arachidonic acid labelled diacylglycerol formation and intracellular levels of inositol phosphates from myo-[2-3H]inositol labelled phospholipids. Phospholipase A2 (PLA2), phosphatidylinositol-specific phospholipase C (PLC), and phospholipase D (PLD) are all activated by stretch. The stretch-induced increases in PG production, 3H-arachidonic acid labelled phospholipid breakdown, and 3H-arachidonic acid labelled diacylglycerol formation occur independently of cellular electrical activity (tetrodotoxin insensitive) whereas the formation of inositol phosphates from myo-[2-3H]inositol labelled phospholipids is dependent on cellular electrical activity. These results indicate that mechanical stimulation increases the lipid-related second messengers arachidonic acid, diacylglycerol, and PG through activation of specific phospholipases such as PLA2 and PLD, but not by activation of phosphatidylinositol-specific PLC.

  20. Functional Analysis of Two PLA2G2A Variants Associated with Secretory Phospholipase A2-IIA Levels

    PubMed Central

    Exeter, Holly J.; Folkersen, Lasse; Palmen, Jutta; Franco-Cereceda, Anders; Cooper, Jackie A.; Kalea, Anastasia Z.; Hooft, Ferdinand van’t; Eriksson, Per; Humphries, Steve E.; Talmud, Philippa J.

    2012-01-01

    Background Secretory phospholipase A2 group IIA (sPLA2-IIA) has been identified as a biomarker of atherosclerosis in observational and animal studies. The protein is encoded by the PLA2G2A gene and the aim of this study was to test the functionality of two PLA2G2A non-coding SNPs, rs11573156 C>G and rs3767221 T>G where the rare alleles have been previously associated with higher and lower sPLA2-IIA levels respectively. Methodology/Principal Findings Luciferase assays, electrophoretic mobility shift assays (EMSA), and RNA expression by RT-PCR were used to examine allelic differences. For rs3767221 the G allele showed ∼55% lower luciferase activity compared to the T allele (T = 62.1 (95% CI 59.1 to 65.1) G = 27.8 (95% CI 25.0 to 30.6), p = 1.22×10−35, and stronger EMSA binding of a nuclear protein compared to the T-allele. For rs11573156 C >G there were no luciferase or EMSA allelic differences seen. In lymphocyte cell RNA, from individuals of known rs11573156 genotype, there was no allelic RNA expression difference for exons 5 and 6, but G allele carriers (n = 7) showed a trend to lower exon 1–2 expression compared to CC individuals. To take this further, in the ASAP study (n = 223), an rs11573156 proxy (r2 = 0.91) showed ∼25% higher liver expression of PLA2G2A (1.67×10−17) associated with the G allele. However, considering exon specific expression, the association was greatly reduced for exon 2 (4.5×10−5) compared to exons 3–6 (10−10 to 10−20), suggesting rs11573156 G allele-specific exon 2 skipping. Conclusion Both SNPs are functional and provide useful tools for Mendelian Randomisation to determine whether the relationship between sPLA2-IIA and coronary heart disease is causal. PMID:22879865