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Sample records for induces phospholipid turnover

  1. Platelet-activating factor induces phospholipid turnover, calcium flux, arachidonic acid liberation, eicosanoid generation, and oncogene expression in a human B cell line

    Energy Technology Data Exchange (ETDEWEB)

    Schulam, P.G.; Kuruvilla, A.; Putcha, G.; Mangus, L.; Franklin-Johnson, J.; Shearer, W.T. (Baylor College of Medicine, Houston, TX (USA))

    1991-03-01

    Platelet-activating factor is a potent mediator of the inflammatory response. Studies of the actions of platelet-activating factor have centered mainly around neutrophils, monocytes, and platelets. In this report we begin to uncover the influence of platelet-activating factor on B lymphocytes. Employing the EBV-transformed human B cell line SKW6.4, we demonstrate that platelet-activating factor significantly alters membrane phospholipid metabolism indicated by the incorporation of 32P into phosphatidylcholine, phosphatidylinositol, and phosphatidic acid but not significantly into phosphatidylethanolamine at concentrations ranging from 10(-9) to 10(-6) M. The inactive precursor, lyso-platelet-activating factor, at a concentration as high as 10(-7) M had no effect on any of the membrane phospholipids. We also show that platelet-activating factor from 10(-12) to 10(-6) M induced rapid and significant elevation in intracellular calcium levels, whereas lyso-platelet-activating factor was again ineffective. We further demonstrate the impact of platelet-activating factor binding to B cells by measuring platelet-activating factor induced arachidonic acid release and 5-hydroxyeicosatetraenoic acid production. Moreover, platelet-activating factor was capable of inducing transcription of the nuclear proto-oncogenes c-fos and c-jun. Finally we explored the possible role of 5-hydroxyeicosatetraenoic acid as a regulator of arachidonic acid liberation demonstrating that endogenous 5-lipoxygenase activity modulates platelet-activating factor induced arachidonic acid release perhaps acting at the level of phospholipase A2. In summary, platelet-activating factor is shown here to have a direct and profound effect on a pure B cell line.

  2. Phospholipide turnover in microsomal membranes of the pancreas during enzyme secretion.

    Science.gov (United States)

    REDMAN, C M; HOKIN, L E

    1959-10-01

    After incubation of pigeon pancreas slices with P(32) and isolation of various fractions by differential centrifugation the deoxycholate extract of the microsome fraction was found to account for over half of the phospholipide P and over half of the P(32) incorporated into the phospholipides. The remaining phospholipide P and P(32) were fairly evenly distributed in the nuclei, zymogen granules, mitochondria, microsomal ribonucleoprotein particles, and the soluble fraction. When enzyme secretion was stimulated with acetylcholine about two-thirds of the increment in radioactivity in the total phospholipides was found in deoxycholate soluble components of the microsome fraction. The remainder of the increment was distributed in the other fractions. This indicates that the cellular component in which the increase in phospholipide turnover occurs on stimulation of secretion is a membranous structure. Evidence is presented which indicates that the increment in radioactivity in the non-microsomal fractions on stimulation of secretion is due to contamination of these fractions with fragments of the stimulated membranous structure. The distribution of P(32) radioactivity in each of the chromatographically separated phospholipides in the various fractions from unstimulated tissue paralleled the distribution of radioactivity in the total phospholipide fraction, indicating that individual phospholipides are not concentrated in different fractions but are associated together in the membranous structures of the microsome fraction. The major proportion of the stimulation of the turnover of the individual phospholipides also occurred in the microsome fraction. The distribution of radioactivity from glycerol-1-C(14) in the total phospholipides and in the individual phospholipides in the various fractions was similar to the distribution of P(32). In the microsome fraction acetylcholine stimulated the incorporation of glycerol-1-C(14) in each phospholipide which showed a stimulation

  3. Alpha-synuclein gene ablation increases docosahexaenoic acid incorporation and turnover in brain phospholipids

    DEFF Research Database (Denmark)

    Golovko, Mikhail Y; Rosenberger, Thad A; Feddersen, Søren

    2007-01-01

    Previously, we demonstrated that ablation of alpha-synuclein (Snca) reduces arachidonate (20:4n-6) turnover in brain phospholipids through modulation of an endoplasmic reticulum-localized acyl-CoA synthetase (Acsl). The effect of Snca ablation on docosahexaenoic acid (22:6n-3) metabolism is unkno...

  4. The Lantibiotic Nisin Induces Transmembrane Movement of a Fluorescent Phospholipid

    NARCIS (Netherlands)

    Moll, Gert N.; Konings, Wil N.; Driessen, Arnold J.M.

    1998-01-01

    Nisin is a pore-forming antimicrobial peptide. The capacity of nisin to induce transmembrane movement of a fluorescent phospholipid in lipid vesicles was investigated. Unilamellar phospholipid vesicles that contained a fluorescent phospholipid

  5. The Lantibiotic Nisin Induces Transmembrane Movement of a Fluorescent Phospholipid

    NARCIS (Netherlands)

    Moll, Gert N.; Konings, Wil N.; Driessen, Arnold J.M.

    1998-01-01

    Nisin is a pore-forming antimicrobial peptide. The capacity of nisin to induce transmembrane movement of a fluorescent phospholipid in lipid vesicles was investigated. Unilamellar phospholipid vesicles that contained a fluorescent phospholipid (1-acyl-2-{6-[(7-nitro-2-1,3-benzoxadiazol-4-yl)amino]ca

  6. Turnover of phosphocholine and phosphoethanolamine in ether-phospholipids of Krebs II ascite cells

    Energy Technology Data Exchange (ETDEWEB)

    Tamer, A.E.; Record, M.; Chap, H.; Douste-Blazy, L.

    1985-10-01

    Krebs II ascite cells suspended in Eagle medium were incubated at 37 C for up to 6 hr in the presence of (TH) glycerol or (TSP) orthophosphate. After extraction, their lipids were treated with guinea pig phospholipase A1 under conditions where all diacyl-phospholipids (diacyl-PL) became hydrolyzed with 55% recovery of lyso-PL. Using a bidimensional thin layer chromatography (TLC) involving exposure to HCl fumes between the two runs, it then became possible to determine at once the specific radioactivity of the three subclasses present in choline glycerophospholipids (CGP) and ethanolamineglycerophospholipids (EGP). Compared to diacyl-PL, a lower de novo synthesis of ether subclasses was evidenced in both CGP and EGP by (TH) glycerol incorporation. Although the same profile was obtained for CGP with (TSP) orthophosphate, the three EGP subclasses displayed in this case the same specific radioactivity. These data indicate a higher turnover rate of the polar head group of ether-EGP compared to either-CGP. The simple methodology used in the present study might thus prove helpful in developing enzymatic studies dealing with the mechanism of this accelerated renewal.

  7. Decrease in membrane phospholipid unsaturation induces unfolded protein response.

    Science.gov (United States)

    Ariyama, Hiroyuki; Kono, Nozomu; Matsuda, Shinji; Inoue, Takao; Arai, Hiroyuki

    2010-07-16

    Various kinds of fatty acids are distributed in membrane phospholipids in mammalian cells and tissues. The degree of fatty acid unsaturation in membrane phospholipids affects many membrane-associated functions and can be influenced by diet and by altered activities of lipid-metabolizing enzymes such as fatty acid desaturases. However, little is known about how mammalian cells respond to changes in phospholipid fatty acid composition. In this study we showed that stearoyl-CoA desaturase 1 (SCD1) knockdown increased the amount of saturated fatty acids and decreased that of monounsaturated fatty acids in phospholipids without affecting the amount or the composition of free fatty acid and induced unfolded protein response (UPR), evidenced by increased expression of C/EBP homologous protein (CHOP) and glucose-regulated protein 78 (GRP78) mRNAs and splicing of Xbox-binding protein 1 (XBP1) mRNA. SCD1 knockdown-induced UPR was rescued by various unsaturated fatty acids and was enhanced by saturated fatty acid. Lysophosphatidylcholine acyltransferase 3 (LPCAT3), which incorporates preferentially polyunsaturated fatty acids into phosphatidylcholine, was up-regulated in SCD1 knockdown cells. Knockdown of LPCAT3 synergistically enhanced UPR with SCD1 knockdown. Finally we showed that palmitic acid-induced UPR was significantly enhanced by LPCAT3 knockdown as well as SCD1 knockdown. These results suggest that a decrease in membrane phospholipid unsaturation induces UPR.

  8. Drug induced `softening' in phospholipid monolayers

    Science.gov (United States)

    Basak, Uttam Kumar; Datta, Alokmay; Bhattacharya, Dhananjay

    2015-06-01

    Compressibility measurements on Langmuir monolayers of the phospholipid Dimystoryl Phospatidylcholine (DMPC) in pristine form and in the presence of the Non-steroidal Anti-inflammatory Drug (NSAID) Piroxicam at 0.025 drug/lipid (D/L) molecular ratio at different temperatures, show that the monolayer exhibits large increase (and subsequent decrease) in compressibility due to the drug in the vicinity of the Liquid Expanded - Liquid Condensed (LE-LC) phase transition. Molecular dynamics simulations of the lipid monolayer in presence of drug molecules show a disordering of the tail tilt, which is consistent with the above result.

  9. Manganese-induced turnover of TMEM165.

    Science.gov (United States)

    Potelle, Sven; Dulary, Eudoxie; Climer, Leslie; Duvet, Sandrine; Morelle, Willy; Vicogne, Dorothée; Lebredonchel, Elodie; Houdou, Marine; Spriet, Corentin; Krzewinski-Recchi, Marie-Ange; Peanne, Romain; Klein, André; de Bettignies, Geoffroy; Morsomme, Pierre; Matthijs, Gert; Marquardt, Thorsten; Lupashin, Vladimir; Foulquier, François

    2017-04-19

    TMEM165 deficiencies lead to one of the congenital disorders of glycosylation (CDG), a group of inherited diseases where the glycosylation process is altered. We recently demonstrated that the Golgi glycosylation defect due to TMEM165 deficiency resulted from a Golgi manganese homeostasis defect and that Mn(2+) supplementation was sufficient to rescue normal glycosylation. In the present paper, we highlight TMEM165 as a novel Golgi protein sensitive to manganese. When cells were exposed to high Mn(2+) concentrations, TMEM165 was degraded in lysosomes. Remarkably, while the variant R126H was sensitive upon manganese exposure, the variant E108G, recently identified in a novel TMEM165-CDG patient, was found to be insensitive. We also showed that the E108G mutation did not abolish the function of TMEM165 in Golgi glycosylation. Altogether, the present study identified the Golgi protein TMEM165 as a novel Mn(2+)-sensitive protein in mammalian cells and pointed to the crucial importance of the glutamic acid (E108) in the cytosolic ELGDK motif in Mn(2+)-induced degradation of TMEM165. © 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

  10. Herpes simplex virus 1 induces de novo phospholipid synthesis

    Energy Technology Data Exchange (ETDEWEB)

    Sutter, Esther [Electron Microscopy, Institute of Veterinary Anatomy, University of Zuerich (Switzerland); Oliveira, Anna Paula de; Tobler, Kurt [Electron microscopy, Institute of Virology, University of Zuerich (Switzerland); Schraner, Elisabeth M. [Electron Microscopy, Institute of Veterinary Anatomy, University of Zuerich (Switzerland); Sonda, Sabrina [Institute of Parasitology, University of Zuerich (Switzerland); Kaech, Andres [Center for Microscopy and Image Analysis, University of Zuerich (Switzerland); Lucas, Miriam S. [Electron Microscopy ETH Zuerich (EMEZ), Swiss Federal Institute of Technology, Zuerich (Switzerland); Ackermann, Mathias [Electron microscopy, Institute of Virology, University of Zuerich (Switzerland); Wild, Peter, E-mail: pewild@access.uzh.ch [Electron Microscopy, Institute of Veterinary Anatomy, University of Zuerich (Switzerland)

    2012-08-01

    Herpes simplex virus type 1 capsids bud at nuclear membranes and Golgi membranes acquiring an envelope composed of phospholipids. Hence, we measured incorporation of phospholipid precursors into these membranes, and quantified changes in size of cellular compartments by morphometric analysis. Incorporation of [{sup 3}H]-choline into both nuclear and cytoplasmic membranes was significantly enhanced upon infection. [{sup 3}H]-choline was also part of isolated virions even grown in the presence of brefeldin A. Nuclei expanded early in infection. The Golgi complex and vacuoles increased substantially whereas the endoplasmic reticulum enlarged only temporarily. The data suggest that HSV-1 stimulates phospholipid synthesis, and that de novo synthesized phospholipids are inserted into nuclear and cytoplasmic membranes to i) maintain membrane integrity in the course of nuclear and cellular expansion, ii) to supply membrane constituents for envelopment of capsids by budding at nuclear membranes and Golgi membranes, and iii) to provide membranes for formation of transport vacuoles.

  11. Salicylic acid induces vanillin synthesis through the phospholipid signaling pathway in Capsicum chinense cell cultures.

    Science.gov (United States)

    Rodas-Junco, Beatriz A; Cab-Guillén, Yahaira; Muñoz-Sánchez, J Armando; Vázquez-Flota, Felipe; Monforte-González, Miriam; Hernández-Sotomayor, S M Teresa

    2013-10-01

    Signal transduction via phospholipids is mediated by phospholipases such as phospholipase C (PLC) and D (PLD), which catalyze hydrolysis of plasma membrane structural phospholipids. Phospholipid signaling is also involved in plant responses to phytohormones such as salicylic acid (SA). The relationships between phospholipid signaling, SA, and secondary metabolism are not fully understood. Using a Capsicum chinense cell suspension as a model, we evaluated whether phospholipid signaling modulates SA-induced vanillin production through the activation of phenylalanine ammonia lyase (PAL), a key enzyme in the biosynthetic pathway. Salicylic acid was found to elicit PAL activity and consequently vanillin production, which was diminished or reversed upon exposure to the phosphoinositide-phospholipase C (PI-PLC) signaling inhibitors neomycin and U73122. Exposure to the phosphatidic acid inhibitor 1-butanol altered PLD activity and prevented SA-induced vanillin production. Our results suggest that PLC and PLD-generated secondary messengers may be modulating SA-induced vanillin production through the activation of key biosynthetic pathway enzymes.

  12. Carbachol-induced phosphoinositide turnover in NCB-20 cells

    Energy Technology Data Exchange (ETDEWEB)

    Chuang, D.M.; Dillon-Carter, O.

    1986-03-01

    NCB-20 cells (fetal Chinese hamster brain cell x neuroblastoma hybrids) have been shown to contain a variety of neurotransmitter receptors. The authors now report that this cloned cell line also contains acetylcholne receptors which are linked to phospholipase C. Confluent cell cultures were preincubated with /sup 3/H-myo-inositol to label endogenous phosphoinositide (PI) and the accumulation of a PI metabolite, inositol monophosphate (IP/sub 1/), was measured in the presence of LiCl. Carbachol increased IP/sub 1/), accumulation be more than 400% with a EC/sub 50/ of about 50 ..mu..M. Acetylcholine and muscarine were also effective, whereas oxotremorine and McN-A-343 were weak in both potency and efficacy. The carbachol-induced IP/sub 1/ accumulation was completely blocked by atropine (Ki approx. 0.6 nM) and pirenzepine (Ki approx. 15 nM). The presence of KCl was not required for the carbachol-induced effect. The formation of inositol bis- and triphosphate was also increased carbachol; these increases occurred earlier but were of much smaller magnitude. Pretreatment of cells with 4 ..beta..-phorbol dibutyrate or 4 ..beta..-phorbol myristate acetate was found to attenuate the carbachol-induced formation of IP/sub 1/ (IC/sub 50/ in the low nanomolar concentration ranges), however 4 ..beta..-phorbol, the biologically inactive phorbol ester, was ineffective in causing this attenuation. These results suggest a feedback inhibition of PI turnover in NCB-20 cells through the action of protein kinase C.

  13. Aggregation of phospholipid vesicles induced by the ribosome inactivating protein saporin.

    Science.gov (United States)

    Hao, Q; Yan, L; Yang, H; Zhang, Y; Gao, G; Yao, Q; Li, Q

    1996-04-01

    Saporin-S6(SO-6) is a single chain ribosome inactivating protein, which can inhibit protein synthesis by inactivating eukaryotic ribosomes. The interaction of SO-6 with phospholipid model systems was described. SO-6 can specifically interact with negatively-charged phospholipid vesicles and it induces the aggregation of the lipid vesicles. The kinetics of the vesicle aggregation induced by SO-6 was studied. The saturating protein/lipid molar ratio was determined to be 1:100 based on titration experiments. The aggregation is dependent on the temperature in a range that was many times higher than the phase transition temperature of the phospholipid. The effect of pH on the aggregation of the vesicles can not be explained by simple deprotonation of side chain amino groups of the protein, and may be related to conformational changes of the protein. The maintenance of physiological ionic strength was required for the aggregation of SO-6 with vesicles. Finally, the interaction was prompted by Ca2+ ions, and was totally inhibited by EDTA, which suggests that SO-6 may interact with phospholipid vesicles in a Ca(2+)-dependent manner.

  14. Fusion of phospholipid vesicles induced by muscle glyceraldehyde-3-phosphate dehydrogenase in the absence of calcium.

    Science.gov (United States)

    Morero, R D; Viñals, A L; Bloj, B; Farías, R N

    1985-04-01

    Ca2+-induced fusion of phospholipid vesicles (phosphatidylcholine/phosphatidic acid, 9:1 mol/mol) prepared by ethanolic injection was followed by five different procedures: resonance energy transfer, light scattering, electron microscopy, intermixing of aqueous content, and gel filtration through Sepharose 4-B. The five methods gave concordant results, showing that vesicles containing only 10% phosphatidic acid can be induced to fuse by millimolar concentrations of Ca2+. When the fusing capability of several soluble proteins was assayed, it was found that concanavalin A, bovine serum albumin, ribonuclease, and protease were inactive. On the other hand, lysozyme, L-lactic dehydrogenase, and muscle and yeast glyceraldehyde-3-phosphate dehydrogenase were capable of inducing vesicle fusion. Glyceraldehyde-3-phosphate dehydrogenase from rabbit muscle, the most extensively studied protein, proved to be very effective: 0.1 microM was enough to induce complete intermixing of bilayer phospholipid vesicles. Under conditions used in this work, fusion was accompanied by leakage of internal contents. The fusing capability of glyceraldehyde-3-phosphate dehydrogenase was not affected by 5 mM ethylenediaminetetraacetic acid. The Ca2+ concentration in the medium, as determined by atomic absorption spectroscopy, was 5 ppm. Heat-denatured enzyme was incapable of inducing fusion. We conclude that glyceraldehyde-3-phosphate dehydrogenase is a soluble protein inherently endowed with the capability of fusing phospholipid vesicles.

  15. Osmotically induced cell swelling versus cell shrinking elicits specific changes in phospholipid signals in tobacco pollen tubes

    NARCIS (Netherlands)

    L.E. Zonia; T. Munnik

    2004-01-01

    Pollen tube cell volume changes rapidly in response to perturbation of the extracellular osmotic potential. This report shows that specific phospholipid signals are differentially stimulated or attenuated during osmotic perturbations. Hypo-osmotic stress induces rapid increases in phosphatidic acid

  16. Lowering of plasma phospholipid transfer protein activity by acute hyperglycaemia-induced hyperinsulinaemia in healthy men

    NARCIS (Netherlands)

    vanTol, A; Ligtenberg, JJM; Riemens, SC; vanHaeften, TW; Dullaart, RPF

    1997-01-01

    Human plasma contains two lipid transfer proteins involved in the remodelling of plasma lipoproteins: cholesteryl ester transfer protein (CETP) and phospholipid transfer protein (PLTP). CETP mediates the transfer/exchange of cholesterylesters, triglycerides and phospholipids between high-density lip

  17. Salicylic acid induces vanillin synthesis through the phospholipid signaling pathway in Capsicum chinense cell cultures

    Science.gov (United States)

    Rodas-Junco, Beatriz A; Cab-Guillen, Yahaira; Muñoz-Sanchez, J Armando; Vázquez-Flota, Felipe; Monforte-Gonzalez, Miriam; Hérnandez-Sotomayor, S M Teresa

    2013-01-01

    Signal transduction via phospholipids is mediated by phospholipases such as phospholipase C (PLC) and D (PLD), which catalyze hydrolysis of plasma membrane structural phospholipids. Phospholipid signaling is also involved in plant responses to phytohormones such as salicylic acid (SA). The relationships between phospholipid signaling, SA, and secondary metabolism are not fully understood. Using a Capsicum chinense cell suspension as a model, we evaluated whether phospholipid signaling modulates SA-induced vanillin production through the activation of phenylalanine ammonia lyase (PAL), a key enzyme in the biosynthetic pathway. Salicylic acid was found to elicit PAL activity and consequently vanillin production, which was diminished or reversed upon exposure to the phosphoinositide-phospholipase C (PI-PLC) signaling inhibitors neomycin and U73122. Exposure to the phosphatidic acid inhibitor 1-butanol altered PLD activity and prevented SA-induced vanillin production. Our results suggest that PLC and PLD-generated secondary messengers may be modulating SA-induced vanillin production through the activation of key biosynthetic pathway enzymes.

  18. Urea-induced Inactivation and Unfolding of Recombinant Phospholipid Hydroperoxide Glutathione Peroxidase from Oryza sativa

    Institute of Scientific and Technical Information of China (English)

    WANG Feng; ZHOU Hui-ping; KONG Bao-hua; FAN Jing-hua; CHEN Hai-ru; LIU Jin-yuan

    2007-01-01

    Phospholipid hydroperoxide glutathione peroxidase is an antioxidant enzyme that has the highest capability of reducing membrane-bound hydroperoxy lipids as compared to free organic and inorganic hydroperoxides amongst the glutathione peroxidases. In this study, urea-induced effects on the inactivation and unfolding of a recombinant phospholipid hydroperoxide glutathione peroxidase(PHGPx) from Oryza sativa were investigated by means of circular dichroism and fluorescence spectroscopy. With the increase of urea concentration, the residual activity of OsPHGPx decreasea correspondingly. When the urea concentration is above 5.0 mol/L, there was no residual activity. In addition,the observed changes in intrinsic tryptophan fluorescence, the binding of the hydrophobic fluorescence probe ANS,and the far UV CD describe a common dependence on the concentration of urea suggesting that the conformational features of the native OsPHGPx are lost in a highly cooperative single transition. The unfolding process comprises of three zones: the native base-line zone between 0 and 2.5 mol/L urea, the transition zone between 2.5 and 5.5 mol/L urea, and the denatured base-line zone above 5.5 mol/L urea. The transition zone has a midpoint at about 4.0 mol/L urea.

  19. Analysis of the Role of Insulin Signaling in Bone Turnover Induced by Fluoride.

    Science.gov (United States)

    Liu, Qinyi; Liu, Hui; Yu, Xiuhua; Wang, Yan; Yang, Chen; Xu, Hui

    2016-06-01

    The role of insulin signaling on the mechanism underlying fluoride induced osteopathology was studied. We analyzed the expression of genes related with bone turnover and insulin signaling in rats treated by varying dose of fluoride with or without streptozotocin (STZ) in vivo. Furthermore, insulin receptor (InR) expression in MC3T3-E1 cells (pre-osteoblast cell line) was interfered with small interfering RNA (siRNA), and genes related with osteoblastic and osteoclastic differentiation were investigated in cells exposed to fluoride in vitro for 2 days. The in vivo study indicated the possible role of insulin in bone lesion induced by excessive amount of fluoride. Fluoride activated the InR and Insulin-like growth factor 1 (IGF1) signaling, which were involved in the mechanism underlying fluoride induced bone turnover. The TGFβ1 and Wnt10/β-catenin pathway took part in the mechanism of bone lesion induced by fluoride, and insulin probably modulated the TGFβ1 and β-catenin to exert action on bone turnover during the development of bone lesion. The in vitro study showed the concomitant decrease of OPG, osterix and OCN with inhibition of InR expression in osteoblast, and three genes still was low in cells co-treated with fluoride and InR siRNA, which suggested that fluoride probably stimulated the expression of OPG, osterix and OCN through InR signaling. In conclusion, insulin played the important role in bone lesion induced by excessive amount of fluoride through mediating InR receptor signaling, and IGF1 signaling probably exerted action on bone turnover caused by overdose of fluoride.

  20. Lipolysis in lipid turnover, cancer cachexia, and obesity-induced insulin resistance.

    Science.gov (United States)

    Arner, Peter; Langin, Dominique

    2014-05-01

    Triglycerides in adipose tissue are rapidly mobilized during times of energy needs via lipolysis, a catabolic process that plays important role in whole body triglyceride turnover. Lipolysis is regulated through cell surface receptors via neurotransmitters, hormones, and paracrine factors that activate various intracellular pathways. These pathways converge on the lipid droplet, the site of action of lipases and cofactors. Fat cell lipolysis is also involved in the pathogenesis of metabolic disorders, and recent human studies have underscored its role in disease states such as cancer cachexia and obesity-induced insulin resistance. We highlight here topics and findings with physiological and clinical relevance, namely lipid turnover in human fat cells and the role of lipolysis in cancer cachexia and obesity-induced insulin resistance. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. CA2+-INDUCED FUSION OF PHOSPHOLIPID-VESICLES CONTAINING FREE FATTY-ACIDS - MODULATION BY TRANSMEMBRANE PH GRADIENTS

    NARCIS (Netherlands)

    WILSCHUT, J; SCHOLMA, J; EASTMAN, SJ; HOPE, MJ; CULLIS, PR

    1992-01-01

    The influence of a transmembrane pH gradient on the Ca2+-induced fusion of phospholipid vesicles, containing free fatty acids, has been investigated. Large unilamellar vesicles composed of an equimolar mixture of cardiolipin, dioleoylphosphatidylcholine, and cholesterol, containing 20 mol % oleic ac

  2. Arthritis induces early bone high turnover, structural degradation and mechanical weakness.

    Directory of Open Access Journals (Sweden)

    Bruno Vidal

    Full Text Available We have previously found in the chronic SKG mouse model of arthritis that long standing (5 and 8 months inflammation directly leads to high collagen bone turnover, disorganization of the collagen network, disturbed bone microstructure and degradation of bone biomechanical properties. The main goal of the present work was to study the effects of the first days of the inflammatory process on the microarchitecture and mechanical properties of bone.Twenty eight Wistar adjuvant-induced arthritis (AIA rats were monitored during 22 days after disease induction for the inflammatory score, ankle perimeter and body weight. Healthy non-arthritic rats were used as controls for compar-ison. After 22 days of disease progression rats were sacrificed and bone samples were collected for histomorphometrical, energy dispersive X-ray spectroscopical analysis and 3-point bending. Blood samples were also collected for bone turnover markers.AIA rats had an increased bone turnover (as inferred from increased P1NP and CTX1, p = 0.0010 and p = 0.0002, respectively and this was paralleled by a decreased mineral content (calcium p = 0.0046 and phos-phorus p = 0.0046. Histomorphometry showed a lower trabecular thickness (p = 0.0002 and bone volume (p = 0.0003 and higher trabecular sepa-ration (p = 0.0009 in the arthritic group as compared with controls. In addition, bone mechanical tests showed evidence of fragility as depicted by diminished values of yield stress and ultimate fracture point (p = 0.0061 and p = 0.0279, re-spectively in the arthritic group.We have shown in an AIA rat model that arthritis induc-es early bone high turnover, structural degradation, mineral loss and mechanical weak-ness.

  3. Arthritis induces early bone high turnover, structural degradation and mechanical weakness.

    Science.gov (United States)

    Vidal, Bruno; Cascão, Rita; Vale, Ana Catarina; Cavaleiro, Inês; Vaz, Maria Fátima; Brito, José Américo Almeida; Canhão, Helena; Fonseca, João Eurico

    2015-01-01

    We have previously found in the chronic SKG mouse model of arthritis that long standing (5 and 8 months) inflammation directly leads to high collagen bone turnover, disorganization of the collagen network, disturbed bone microstructure and degradation of bone biomechanical properties. The main goal of the present work was to study the effects of the first days of the inflammatory process on the microarchitecture and mechanical properties of bone. Twenty eight Wistar adjuvant-induced arthritis (AIA) rats were monitored during 22 days after disease induction for the inflammatory score, ankle perimeter and body weight. Healthy non-arthritic rats were used as controls for compar-ison. After 22 days of disease progression rats were sacrificed and bone samples were collected for histomorphometrical, energy dispersive X-ray spectroscopical analysis and 3-point bending. Blood samples were also collected for bone turnover markers. AIA rats had an increased bone turnover (as inferred from increased P1NP and CTX1, p = 0.0010 and p = 0.0002, respectively) and this was paralleled by a decreased mineral content (calcium p = 0.0046 and phos-phorus p = 0.0046). Histomorphometry showed a lower trabecular thickness (p = 0.0002) and bone volume (p = 0.0003) and higher trabecular sepa-ration (p = 0.0009) in the arthritic group as compared with controls. In addition, bone mechanical tests showed evidence of fragility as depicted by diminished values of yield stress and ultimate fracture point (p = 0.0061 and p = 0.0279, re-spectively) in the arthritic group. We have shown in an AIA rat model that arthritis induc-es early bone high turnover, structural degradation, mineral loss and mechanical weak-ness.

  4. Lipid asymmetry in plant plasma membranes: phosphate deficiency-induced phospholipid replacement is restricted to the cytosolic leaflet

    DEFF Research Database (Denmark)

    Tjällström, H; Hellgren, Lars; Wieslander, Å;

    2010-01-01

    barrier) and rafts both contain only trace amounts of DGDG, we conclude that this lipid class is not compatible with membrane functions requiring a high degree of lipid order. By not replacing phospholipids site specifically with DGDG, negative functional effects of this lipid in the plasma membrane...... are avoided.-Tjellström, H., Hellgren, L. I., Wieslander, A., Sandelius, A. S. Lipid asymmetry in plant plasma membranes: phosphate deficiency-induced phospholipid replacement is restricted to the cytosolic leaflet.......As in other eukaryotes, plant plasma membranes contain sphingolipids, phospholipids, and free sterols. In addition, plant plasma membranes also contain sterol derivatives and usually 5 mol% DGDG was included. As both the apoplastic plasma membrane leaflet (probably the major water permeability...

  5. Improved mitochondrial function with diet-induced increase in either docosahexaenoic acid or arachidonic acid in membrane phospholipids.

    Directory of Open Access Journals (Sweden)

    Ramzi J Khairallah

    Full Text Available Mitochondria can depolarize and trigger cell death through the opening of the mitochondrial permeability transition pore (MPTP. We recently showed that an increase in the long chain n3 polyunsaturated fatty acids (PUFA docosahexaenoic acid (DHA; 22:6n3 and depletion of the n6 PUFA arachidonic acid (ARA; 20:4n6 in mitochondrial membranes is associated with a greater Ca(2+ load required to induce MPTP opening. Here we manipulated mitochondrial phospholipid composition by supplementing the diet with DHA, ARA or combined DHA+ARA in rats for 10 weeks. There were no effects on cardiac function, or respiration of isolated mitochondria. Analysis of mitochondrial phospholipids showed DHA supplementation increased DHA and displaced ARA in mitochondrial membranes, while supplementation with ARA or DHA+ARA increased ARA and depleted linoleic acid (18:2n6. Phospholipid analysis revealed a similar pattern, particularly in cardiolipin. Tetralinoleoyl cardiolipin was depleted by 80% with ARA or DHA+ARA supplementation, with linoleic acid side chains replaced by ARA. Both the DHA and ARA groups had delayed Ca(2+-induced MPTP opening, but the DHA+ARA group was similar to the control diet. In conclusion, alterations in mitochondria membrane phospholipid fatty acid composition caused by dietary DHA or ARA was associated with a greater cumulative Ca(2+ load required to induced MPTP opening. Further, high levels of tetralinoleoyl cardiolipin were not essential for normal mitochondrial function if replaced with very-long chain n3 or n6 PUFAs.

  6. High bone turnover elevates the risk of denosumab-induced hypocalcemia in women with postmenopausal osteoporosis.

    Science.gov (United States)

    Ishikawa, Koji; Nagai, Takashi; Sakamoto, Keizo; Ohara, Kenji; Eguro, Takeshi; Ito, Hiroshi; Toyoshima, Yoichi; Kokaze, Akatsuki; Toyone, Tomoaki; Inagaki, Katsunori

    2016-01-01

    Hypocalcemia is the most common major adverse event in patients with osteoporosis receiving the bone resorption inhibitor denosumab; however, limited information is available regarding risk factors of hypocalcemia. Therefore, this study aimed to identify the risk factors of hypocalcemia induced by denosumab treatment for osteoporosis. We retrospectively reviewed the records of patients who had received initial denosumab supplemented with activated vitamin D for osteoporosis. Serum levels of the following bone turnover markers (BTMs) were measured at baseline: bone-specific alkaline phosphatase (BAP), total N-terminal propeptide of type 1 procollagen (P1NP), tartrate-resistant acid phosphatase 5b (TRACP-5b), and urinary cross-linked N-telopeptide of type 1 collagen (NTX). Of the 85 denosumab-treated patients with osteoporosis studied, 22 (25.9%) developed hypocalcemia. Baseline serum total P1NP, TRACP-5b, and urinary NTX were significantly higher in patients with hypocalcemia than in those with normocalcemia following denosumab administration (all P76.5 μg/L, TRACP-5b >474 mU/dL, or urinary NTX >49.5 nmol bone collagen equivalent/mmol creatinine had a higher risk of hypocalcemia (Posteoporosis with higher baseline bone turnover than in patients with postmenopausal osteoporosis with normal baseline bone turnover, because maintenance of normal serum calcium in this subgroup is more dependent on bone resorption. Close monitoring of serum calcium levels is strongly recommended for denosumab-treated patients with high bone turnover, despite supplementation with activated vitamin D and oral calcium.

  7. Tip-induced deformation of a phospholipid bilayer: Theoretical perspective of sum frequency generation imaging

    Energy Technology Data Exchange (ETDEWEB)

    Volkov, Victor [Bereozovaya 2A, Konstantinovo, Moscow Region 140207 (Russian Federation)

    2014-10-21

    The paper addresses theory of Sum Frequency Generation imaging of an atomic force microscopy tip-induced deformation of a bilayer phospholipid membrane deposited over a pore: known as a nano-drum system. Image modeling employed nonlinearities of the normal modes specific to hydrocarbon terminal methyls, which are distributed about the deformed surfaces of inner and outer leaflets. The deformed profiles are according to the solutions of shape equation for Canham-Helfrich Hamiltonian accounting properties of four membranes, which differ in elasticity and adhesion. The results indicate that in continuous deformed surfaces, the difference in the curvature of the outer and inner leaflets dominates in the imaged nonlinearity. This is different comparing to the results for a perfect bilayer spherical cap system (the subject of previous study), where nonlinear image response is dominated by the mismatch of the inner and outer leaflets’ surface areas (as projected to the image plane) at the edge of perfectly spherical structure. The results of theoretical studies, here, demonstrate that Sum Frequency Generation imaging in continuous and deformed bilayer surfaces are helpful to address curvature locally and anticipate mechanical properties of membrane. The articles discuss applicability and practical limitations of the approach. Combination of Atomic Force Microscopy and Sum Frequency Generation imaging under controlled tip-induced deformation provides a good opportunity to probe and test membranes physical properties with rigor of adopted theory.

  8. Hepatocyte Turnover in Chronic HCV-Induced Liver Injury and Cirrhosis

    Directory of Open Access Journals (Sweden)

    Nikolaos P. Karidis

    2015-01-01

    Full Text Available Chronic hepatitis C virus (HCV infection may eventually lead to progressive liver fibrosis and cirrhosis through a complex, multistep process involving hepatocyte death and regeneration. Despite common pathogenetic pathways present in all forms of liver cirrhosis irrespective of etiology, hepatocyte turnover and related molecular events in HCV-induced cirrhosis are increasingly being distinguished from even “similar” causes, such as hepatitis B virus- (HBV- related cirrhosis. New insights in HCV-induced hepatocellular injury, differential gene expression, and regenerative pathways have recently revealed a different pattern of progression to irreversible parenchymal liver damage. A shift to the significant role of the host immune response rather than the direct effect of HCV on hepatocytes and the imbalance between antiapoptotic and proapoptotic signals have been investigated in several studies but need to be further elucidated. The present review aims to comprehensively summarize the current evidence on HCV-induced hepatocellular turnover with a view to outline the significant trends of ongoing research.

  9. Phospholipid scramblase expression in the pregnant mouse uterus in LPS-induced preterm delivery.

    Science.gov (United States)

    McLean, Kelley C; Oppenheimer, Karen H; Sweet, Leigh M; Phillippe, Mark

    2012-11-01

    Phospholipid scramblases (PLSCR), stimulated by proinflammatory cytokines, are thought to mediate the loss of lipid asymmetry in cell membranes, allowing for specific reactions in the coagulation cascade. The PLSCR may therefore provide a link between inflammation, coagulation, and, because thrombin is a uterotonic, preterm birth (PTB). To explore the relationship between PLSCR expression and inflammation-related PTB, we utilized reverse transcriptase-polymerase chain reaction and Western blot studies to quantify messenger RNA (mRNA) and protein expression for the 4 PLSCR homologues (PLSCR 1-4). Uteri from day 15 pregnant mice were harvested at several time points after intrauterine lipopolysaccharide (LPS) injection (or normal saline, for controls). Expression of mRNA in all 4 Plscr isoforms was demonstrated. Lipopolysaccharide treatment resulted in increased expression of PLSCR-1 and a decrease in Plscr4 mRNA, thereby demonstrating modulation of PLSCR-1 and PLSCR-4 in LPS-induced PTB. Additionally, protein expression was confirmed for all except PLSCR-4, with increased expression of PLSCR-1 after LPS treatment.

  10. Time resolved studies of interfacial reactions of ozone with pulmonary phospholipid surfactants using field induced droplet ionization mass spectrometry.

    Science.gov (United States)

    Kim, Hugh I; Kim, Hyungjun; Shin, Young Shik; Beegle, Luther W; Goddard, William A; Heath, James R; Kanik, Isik; Beauchamp, J L

    2010-07-29

    Field induced droplet ionization mass spectrometry (FIDI-MS) comprises a soft ionization method to sample ions from the surface of microliter droplets. A pulsed electric field stretches neutral droplets until they develop dual Taylor cones, emitting streams of positively and negatively charged submicrometer droplets in opposite directions, with the desired polarity being directed into a mass spectrometer for analysis. This methodology is employed to study the heterogeneous ozonolysis of 1-palmitoyl-2-oleoyl-sn-phosphatidylglycerol (POPG) at the air-liquid interface in negative ion mode using FIDI mass spectrometry. Our results demonstrate unique characteristics of the heterogeneous reactions at the air-liquid interface. We observe the hydroxyhydroperoxide and the secondary ozonide as major products of POPG ozonolysis in the FIDI-MS spectra. These products are metastable and difficult to observe in the bulk phase, using standard electrospray ionization (ESI) for mass spectrometric analysis. We also present studies of the heterogeneous ozonolysis of a mixture of saturated and unsaturated phospholipids at the air-liquid interface. A mixture of the saturated phospholipid 1,2-dipalmitoyl-sn-phosphatidylglycerol (DPPG) and unsaturated POPG is investigated in negative ion mode using FIDI-MS while a mixture of 1,2-dipalmitoyl-sn-phosphatidylcholine (DPPC) and 1-stearoyl-2-oleoyl-sn-phosphatidylcholine (SOPC) surfactant is studied in positive ion mode. In both cases FIDI-MS shows the saturated and unsaturated pulmonary surfactants form a mixed interfacial layer. Only the unsaturated phospholipid reacts with ozone, forming products that are more hydrophilic than the saturated phospholipid. With extensive ozonolysis only the saturated phospholipid remains at the droplet surface. Combining these experimental observations with the results of computational analysis provides an improved understanding of the interfacial structure and chemistry of a surfactant layer system when

  11. Changes induced by sodium cromoglycate in brain catecholamine turnover in morphine dependent and abstinent mice.

    Science.gov (United States)

    San-Martín-Clark, O; Cuéllar, B; De Alba, J; Leza, J C; Lorenzo, P

    1995-04-01

    The effects of sodium cromoglycate (CRO) were studied in relation to the metabolism of brain catecholamines: dopamine (DA) and noradrenaline (NA), and their metabolites 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 4-hydroxy-3-methoxyphenylethyleneglycol (MHPG). CRO was injected SC in control mice, morphine-tolerant mice (tolerance was induced by SC implantation of a 75 mg morphine pellet; CRO was administered on day 4 of addiction) and 30 min before abstinence (withdrawal was induced by SC injection of naloxone (1 mg/kg) on day 4 of addiction). Brain catecholamines and their metabolites were measured using high performance liquid chromatography coupled with electrochemical detection (HPLC-ECD), for DA, NA, DOPAC and HVA, and coupled with fluorescence detection for MHPG. The ratios of DOPAC + HVA/DA and MHPG/NA were kept as an index of DA and NA turnovers, respectively. CRO administered 30 min before naloxone-precipitated withdrawal diminished significantly NA levels in frontal cortex. CRO increased DA turnover in striatum and frontal cortex in naive animals and significantly diminished DA levels in frontal cortex and DOPAC levels in frontal cortex and midbrain in morphine-dependent mice. These findings are discussed in relation to the protective effects of CRO on opiate withdrawal and the effects of CRO on locomotor activity.

  12. Changes induced by sodium cromoglycate on brain serotonin turnover in morphine dependent and abstinent mice.

    Science.gov (United States)

    San-Martin-Clark, O; Leza, J C; Lizasoain, I; Lorenzo, P

    1993-01-01

    This study was designed to explain the action of sodium cromoglycate (CRO) on the brain serotonergic system in control, morphine tolerant (by SC implantation of a 75 mg morphine pellet), and also in morphine dependent mice just before naloxone-precipitated withdrawal. After SC injections of CRO in control mice, morphine tolerant mice (day 4 of addiction), and 1 h before abstinence (withdrawal was induced by SC injection of 1 mg/kg naloxone on day 4 of addiction), animals were decapitated and various brain areas were rapidly removed. 5HT (Serotonin) and 5HIAA (5-hydroxyindole-3-acetic acid) were measured by high performance liquid chromatography coupled with electrochemical detection (HPLC-ECD). The ratio 5HIAA/5HT provided one index by which the turnover of the indoleamine was measured. CRO increased the turnover of 5HT in most of the brain areas studied in both control and morphine dependent mice. Furthermore, previous administration of CRO prior to naloxone challenge induced a significant increase in the 5HIAA/5HT ratio in the hypothalamus and striatum. These results are discussed as the reason for the preventive effect of CRO on jumping behaviour in morphine abstinent mice.

  13. Development of analytical procedures to study changes in the composition of meat phospholipids caused by induced oxidation.

    Science.gov (United States)

    Cascone, Annunziata; Eerola, Susanna; Ritieni, Alberto; Rizzo, Aldo

    2006-07-07

    Lipid peroxidation affects quality of meat products. The aim of this study was to develop a model system and analytical procedures for evaluating the oxidation level of meat samples, by studying the changes in meat phospholipids (PL) composition and the compounds generated by induced oxidation. Different techniques (liquid-, dry column-, accelerated solvent extraction) were investigated to identify a suitable lipid extraction system for extracting PL from bovine meat and to induce lipid oxidation by using tert-butyl hydroperoxide, 2,2'-azobis(2-amidinopropane) dihydrochloride (ABAP) or Fe(2+) and Cu(2+) salts. Accelerated solvent extraction (ASE) gave results not significantly different from the other extraction methods, but offered the advantage of being a rapid and solvent-saving procedure. The method using a silica column proved to be valid in eluting and separating the components of the phospholipidic fraction and the PL standard mixture. The analytical techniques used to analyse oxidation products of PL included GC-FID, HPLC with corona charged aerosol detector (CAD), MDA determination and the spectrophotometric measurement of peroxide levels (PxL). By means of CAD, PL were quantified and their concentration in the lipid extract was 0.98%+/-0.17 (w/w+/-SD, n=10). The oxidation method induced by ABAP proved to be fast and did not produce any artifacts. Three oxidation times were monitored (0, 90 and 180 min). The oxidation levels after 180 min correlated with a significant increase in the peroxide levels PxL (+71%), MDA (+29%) and aldehydes (+75%), whereas a decrease or even total disappearance of some unsaturated fatty acids was observed. The results obtained demonstrate that the model used in this work is useful for studying oxidation of meat phospholipids. Also, the use of the innovative detector CAD proved to be a good complementary technique in the investigation of lipids.

  14. Cartilage integrity and proteoglycan turnover are comparable in canine experimentally induced and human joint degeneration

    Directory of Open Access Journals (Sweden)

    Femke Intema

    2010-10-01

    Full Text Available The value of experimental models of osteoarthritis (OA largely depends on the ability to translate observations to human OA. Surprisingly, direct comparison of characteristics of human and experimental OA is scarce. In the present study, cartilage integrity and matrix turnover in a canine model of joint degeneration were compared to human clinical OA. In 23 Beagle dogs, joint degeneration was induced in one knee, the contra-lateral knee served as a control. For comparison, human osteoarthritic and healthy knee cartilage were obtained at arthroplasty (n=14 and post-mortem (n=13. Cartilage was analyzed by histology and biochemistry. Values for cartilage integrity and proteoglycan (PG synthesis showed species specific differences; GAG content of healthy cartilage was 2-fold higher in canine cartilage and PG synthesis even 8-fold. However, the relative decrease in PG content between healthy and OA cartilage was similar for humans and canines (-17% vs. -15%, respectively, as was the histological damage (+7.0 vs. +6.1, respectively and the increase of PG synthesis (+100% vs. +70%, respectively. Remarkably, the percentage release of total and of newly formed PGs in human and canine controls was similar, as was the increase due to degeneration (+65% vs. +81% and +91% vs. +52%, respectively. Despite differences in control conditions, the observed changes in characteristics of cartilage integrity and matrix turnover are similar in a canine model of joint degeneration and human clinical OA. The canine Groove model shows that its characteristics reflect those of human OA which makes the model appropriate for studying human OA.

  15. Determination of the phospholipid precursor of anandamide and other N- acylethanolamine phospholipids before and after sodium azide-induced toxicity in cultured neocortical neurons

    DEFF Research Database (Denmark)

    Hansen, H.H.; Schousboe, A.; Hansen, Harald S.;

    2000-01-01

    Phospholipase D-mediated hydrolysis of N-acylethanolamine phospholipids (NAPEs) releases anandamide and other N-acylethanolamines, resulting in different actions at cellular targets in the CNS. Recently, we have demonstrated that these N-acyl lipids accumulate in cultured neocortical neurons...

  16. Gallic acid induces apoptosis in EGFR-mutant non-small cell lung cancers by accelerating EGFR turnover.

    Science.gov (United States)

    Nam, Boas; Rho, Jin Kyung; Shin, Dong-Myung; Son, Jaekyoung

    2016-10-01

    Gallic acid is a common botanic phenolic compound, which is present in plants and foods worldwide. Gallic acid is implicated in various biological processes such as cell growth and apoptosis. Indeed, gallic acid has been shown to induce apoptosis in many cancer types. However, the molecular mechanisms of gallic acid-induced apoptosis in cancer, particularly lung cancer, are still unclear. Here, we report that gallic acid induces apoptosis in EGFR-mutant non-small cell lung cancer (NSCLC) cells, but not in EGFR-WT NSCLC cells. Treatment with gallic acid resulted in a significant reduction in proliferation and induction of apoptosis, only in EGFR-mutant NSCLC cells. Interestingly, treatment with gallic acid led to a robust decrease in EGFR levels, which is critical for NSCLC survival. Treatment with gallic acid had no significant effect on transcription, but induced EGFR turnover. Indeed, treatment with a proteasome inhibitor dramatically reversed gallic acid-induced EGFR downregulation. Moreover, treatment with gallic acid induced EGFR turnover leading to apoptosis in EGFR-TKI (tyrosine kinase inhibitor)-resistant cell lines, which are dependent on EGFR signaling for survival. Thus, these studies suggest that gallic acid can induce apoptosis in EGFR-dependent lung cancers that are dependent on EGFR for growth and survival via acceleration of EGFR turnover.

  17. Prolonged exercise after diuretic-induced hypohydration: effects on substrate turnover and oxidation.

    Science.gov (United States)

    Roy, B D; Green, H J; Burnett, M

    2000-12-01

    To determine the influence of a diuretic-induced reduction in plasma volume (PV) on substrate turnover and oxidation, 10 healthy young males were studied during 60 min of cycling exercise at 61% peak oxygen uptake on two separate occasions > or =1 wk apart. Exercise was performed under control conditions (CON; placebo), and after 4 days of diuretic administration (DIU; Novotriamazide; 100 mg triamterene and 50 mg hydrochlorothiazide). DIU resulted in a calculated reduction of PV by 14.6 +/- 3.3% (P DIU were higher than for CON. No differences were observed in plasma lactate and serum free fatty acid concentrations either at rest or during exercise. Hypohydration led to lower (P DIU than for CON. A similar decline in plasma insulin occurred with exercise in both conditions. These results indicate that diuretic-induced reductions in PV decreases glucose kinetics during moderate-intensity dynamic exercise in the absence of changes in total carbohydrate and fat oxidation. The specific effect on glucose kinetics depends on the duration of the exercise.

  18. Enhanced inositide turnover in brain during bicuculline-induced status epilepticus

    Energy Technology Data Exchange (ETDEWEB)

    Van Rooijen, L.A.; Vadnal, R.; Dobard, P.; Bazan, N.G.

    1986-04-29

    Because brain inositides are enriched in the 1-stearoyl-2-arachidonoyl species, they form a likely source for the tetraenoic free fatty acids (FFA) and diacylglycerols (DG) that are accumulated during seizures. To study inositide turnover during bicuculline-induced seizures, rats were injected intraventricularly and bilaterally with 10-20 microCi /sup 32/P, mechanically ventilated and sacrificed by 6.5 KW head-focused microwave irradiation. Seizure activity was recorded by electroencephalography. Bicuculline-induced seizure activity resulted in: a) almost 50% increase in /sup 32/P labeling of phosphatidic acid (PA); phosphatidylinositol (PI) and phosphatidylinositol 4,5-bisphosphate (PIP2) also increased (24% and 36%, respectively); b) no change in other lipids; and c) water-soluble phosphodiesteratic degradation products, analyzed by high voltage paper electrophoresis, increased 24% in the amount of radiotracer recovered as inositol 1,4-bisphosphate (IP2) and by 44% in the amount recovered as inositol 1,4,5-trisphosphate (IP3). These data indicate that during experimental status epilepticus the cerebral inositide cycle is accelerated: PIP2----(IP3----IP2----IP----I) + DG----PA----PI----PIP----PIP2.

  19. Brain levels of N-acylethanolamine phospholipids in mice during pentylenetetrazol-induced seizure

    DEFF Research Database (Denmark)

    Moesgaard, B.; Hansen, H.H.; Petersen, G.

    2003-01-01

    The N-acylethanolamine phospholipids (NAPE) are precursors for N-acylethanolamines (NAE), including anandamide (20:4-NAE), which is a ligand for the cannabinoid receptors. Previously, NAPE were believed to be found only in injured tissue, e.g., after neurodegenerative insults. Neuronal injury may...... and of N-acyltransferase in brain membrane preparations from adult and 3-d-old mice revealed an enzyme pattern in the adult mice that was favorable for NAE accumulation as opposed to NAPE accumulation. Thus, there was no difference in NAPE levels; at present, however, this does not exclude that NAE may...

  20. Synthetic phosphoethanolamine a precursor of membrane phospholipids reduce tumor growth in mice bearing melanoma B16-F10 and in vitro induce apoptosis and arrest in G2/M phase.

    Science.gov (United States)

    Ferreira, Adilson Kleber; Meneguelo, Renato; Marques, Fabio Luiz Navarro; Radin, Adriano; Filho, Otaviano Mendonça R; Neto, Salvador Claro; Chierice, Gilberto Orivaldo; Maria, Durvanei Augusto

    2012-10-01

    Phosphoethanolamine (Pho-s) is a compound involved in phospholipid turnover, acting as a substrate for many phospholipids of the cell membranes, especially phosphatidylcholine. We recently reported that synthetic Pho-s has potent effects on a wide variety of tumor cells. To determine if Pho-s has a potential antitumor activity, in this study we evaluated the activity of Pho-s against the B16-F10 melanoma both in vitro and in mice bearing a dorsal tumor. The treatment of B16F10 cells with Pho-s resulted in a dose-dependent inhibition of cell proliferation. At low concentrations, this activity appears to be involved in the arrest of the cell cycle at G2/M, while at high concentrations Pho-s induces apoptosis. In accordance with these results, the loss of mitochondrial potential and increased caspase-3 activity suggest that Pho-s has dual antitumor effects; i.e. it induces apoptosis at high concentrations and modulates the cell cycle at lower concentrations. In vivo, we evaluated the effect of Pho-s in mice bearing B16-F10 melanoma. The results show that Pho-s reduces the tumoral volume increasing survival rate. Furthermore, the tumor doubling time and tumor delays were substantially reduced when compared with untreated mice. Histological analyses reveal that Pho-s induces changes in cell morphology, typical characteristics of apoptosis, in addition the large areas of necrosis correlating with a reduction of tumor size. The results presented here support the hypothesis that Pho-s has antitumor effects by the induction of apoptosis as well as the inhibition of cell proliferation by arrest at G2/M. Thus, Pho-s can be regarded as a promising agent for the treatment of melanoma. Published by Elsevier SAS.

  1. Bilobalide, a constituent of Ginkgo biloba, inhibits NMDA-induced phospholipase A2 activation and phospholipid breakdown in rat hippocampus.

    Science.gov (United States)

    Weichel, O; Hilgert, M; Chatterjee, S S; Lehr, M; Klein, J

    1999-12-01

    In rat hippocampal slices superfused with magnesium-free buffer, glutamate (1 mM) caused the release of large amounts of choline due to phospholipid breakdown. This phenomenon was mimicked by N-methyl-D-aspartate (NMDA) in a calcium-sensitive manner and was blocked by NMDA receptor antagonists such as MK-801 and 7-chlorokynurenate. The NMDA-induced release of choline was not caused by activation of phospholipase D but was mediated by phospholipase A2 (PLA2) activation as the release of choline was accompanied by the formation of lyso-phosphatidylcholine (lyso-PC) and glycerophospho-choline (GPCh) and was blocked by 5-[2-(2-carboxyethyl)-4-dodecanoyl-3,5-dimethylpyrrol-1-yl]pentano ic acid, a PLA2 inhibitor. Bilobalide, a constituent of Ginkgo biloba, inhibited the NMDA-induced efflux of choline with an IC50 value of 2.3 microM and also prevented the formation of lyso-PC and GPCh. NMDA also caused a release of choline in vivo when infused into the hippocampus of freely moving rats by retrograde dialysis. Again, the effect was completely inhibited by bilobalide which was administered systemically (20 mg/kg i.p.). Interestingly, convulsions which were observed in the NMDA-treated rats were almost totally suppressed by bilobalide. We conclude that release of choline is a sensitive marker for NMDA-induced phospholipase A2 activation and phospholipid breakdown. Bilobalide inhibited the glutamatergic excitotoxic membrane breakdown both in vitro and in vivo, an effect which may be beneficial in the treatment of brain hypoxia and/or neuronal hyperactivity.

  2. Phospholipid bilayer-perturbing properties underlying lysis induced by pH-sensitive cationic lysine-based surfactants in biomembranes.

    Science.gov (United States)

    Nogueira, Daniele Rubert; Mitjans, Montserrat; Busquets, M Antonia; Pérez, Lourdes; Vinardell, M Pilar

    2012-08-14

    Amino acid-based surfactants constitute an important class of natural surface-active biomolecules with an unpredictable number of industrial applications. To gain a better mechanistic understanding of surfactant-induced membrane destabilization, we assessed the phospholipid bilayer-perturbing properties of new cationic lysine-based surfactants. We used erythrocytes as biomembrane models to study the hemolytic activity of surfactants and their effects on cells' osmotic resistance and morphology, as well as on membrane fluidity and membrane protein profile with varying pH. The antihemolytic capacity of amphiphiles correlated negatively with the length of the alkyl chain. Anisotropy measurements showed that the pH-sensitive surfactants, with the positive charge on the α-amino group of lysine, significantly increased membrane fluidity at acidic conditions. SDS-PAGE analysis revealed that surfactants induced significant degradation of membrane proteins in hypo-osmotic medium and at pH 5.4. By scanning electron microscopy examinations, we corroborated the interaction of surfactants with lipid bilayer. We found that varying the surfactant chemical structure is a way to modulate the positioning of the molecule inside bilayer and, thus, the overall effect on the membrane. Our work showed that pH-sensitive lysine-based surfactants significantly disturb the lipid bilayer of biomembranes especially at acidic conditions, which suggests that these compounds are promising as a new class of multifunctional bioactive excipients for active intracellular drug delivery.

  3. Long-lived reactive species formed on proteins induce changes in protein and lipid turnover.

    Science.gov (United States)

    Davies, Michael

    2014-10-01

    Proteins are major targets for oxidative damage in vivo due to their high abundance and rapid rates of reaction with both one-electron (radical) and two-electron oxidants (e.g. singlet oxygen, hypochlorous acid, peroxynitrous acid, reactive aldehydes). The turnover of both native and modified proteins is critical for maintenance of cell homeostasis, with this occurring via multiple pathways including proteasomes (for cytosolic species), the Lon protease (in mitochondria), and the endo-lysosomal systems (both extra- and intra-cellular species). Evidence has been presented for both enhanced and diminished rates of catabolism of modified proteins, as well as altered turnover of native (unmodified) proteins as a result of damage to these systems, potentially as a result of the accumulation of damaged proteins. In recent studies we have shown that long-lived reactive species forms on proteins (hydroperoxides, chloramines and aldehydes) can modify the activity of proteasomal and lysosomal enzymes. Some of the above species are efficient inhibitors of the tryptic and chymotryptic activities of the 26S proteasome, as well as lysosomal cathepsin and acid lipase activities. These are key species in the turnover of both proteins and lipoproteins. The loss of enzyme activity is accompanied in many cases, by oxidation of critical thiol residues via molecular reactions. For reactive aldehydes (either free or protein-bound) direct enzyme inhibition can occur as well as modulation of protein levels and, in the case of lysosomes, changes in lysosomal numbers. Overall, these data indicate that the formation of reactive species on proteins can modulate cell function by multiple pathways including interference with the turnover of native proteins (including critical cell signalling molecules) and alterations in the rate of clearance of modified proteins. Both pathways may contribute to the development of a number of human pathologies associated with oxidative damage.

  4. Low turnover osteoporosis in sheep induced by hypothalamic-pituitary disconnection.

    Science.gov (United States)

    Beil, Frank Timo; Oheim, Ralf; Barvencik, Florian; Hissnauer, Tim N; Pestka, Jan M; Ignatius, Anita; Rueger, Johannes M; Schinke, Thorsten; Clarke, Iain J; Amling, Michael; Pogoda, Pia

    2012-08-01

    The hypothalamus is of critical importance in regulating bone remodeling. This is underscored by the fact that intracerebroventricular-application of leptin in ewe leads to osteopenia. As a large animal model of osteoporosis, this approach has some limitations, such as high technical expenditure and running costs. Therefore we asked if a surgical ablation of the leptin signaling axis would have the same effects and would thereby be a more useful model. We analyzed the bone phenotype of ewe after surgical hypothalamo-pituitary disconnection (HPD + OVX) as compared to control ewe (OVX) after 3 and 12 months. Analyses included histomorphometric characterization, micro-CT and measurement of bone turnover parameters. Already 3 months after HPD we found osteopenic ewe with a significantly decreased bone formation (69%) and osteoclast activity (49%). After a period of 12 months the HPD group additionally developed an (preclinical) osteoporosis with significant reduction (33%) of femoral cortical thickness, as compared to controls (OVX). Taken together, HPD leads after 12 month to osteoporosis with a reduction in both trabecular and cortical bone caused by a low bone turnover situation, with reduced osteoblast and osteoclast activity, as compared to controls (OVX). The HPD-sheep is a suitable large animal model of osteoporosis. Furthermore our results indicate that an intact hypothalamo-pituitary axis is required for activation of bone turnover.

  5. Quercetin sensitizes pancreatic cancer cells to TRAIL-induced apoptosis through JNK-mediated cFLIP turnover.

    Science.gov (United States)

    Kim, Ji Hye; Kim, Min Joo; Choi, Kyung-Chul; Son, Jaekyoung

    2016-09-01

    Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising anticancer agent that can selectively kill cancer cells. Nonetheless, many cancers are resistant to TRAIL, and the molecular mechanisms of TRAIL resistance in cancer, particularly pancreatic cancer, are still unclear. In this study, we tested the hypothesis that quercetin, a flavonoid, induces apoptosis in TRAIL-resistant pancreatic cancer cells. Although quercetin alone had no significant cytotoxic effect, when combined with TRAIL, it promoted TRAIL-induced apoptosis that required mitochondrial outer membrane permeabilization. A BH3-only protein BID knockdown dramatically attenuated TRAIL/quercetin-induced apoptosis. The expression levels of cellular FLICE-like inhibitory protein (cFLIP) decreased in a dose-dependent manner in the presence of quercetin, and overexpression of cFLIP was able to robustly rescue pancreatic cancer cells from TRAIL/quercetin-induced apoptosis. Additionally, quercetin activated c-Jun N-terminal kinase (JNK) in a dose-dependent manner, which in turn induced the proteasomal degradation of cFLIP, and JNK activation also sensitized pancreatic cancer cells to TRAIL-induced apoptosis. Thus, our results suggest that quercetin induces TRAIL-induced apoptosis via JNK activation-mediated cFLIP turnover. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Effect of Epimedium-derived Phytoestrogen on Bone Turnover and Bone Microarchitecture in OVX-induced Osteoporotic Rats

    Institute of Scientific and Technical Information of China (English)

    Songlin PENG; Renyun XIA; Huang FANG; Feng LI; Anmin CHEN; Ge ZHANG; Ling QIN

    2008-01-01

    To investigate the preventive effect of epimedium-defivod phytoestrogen (PE) on osteoporosis induced by ovariectomy (OVX) in rats, 11-month-old female Wistar rats were randomly di- vided into Sham, OVX and PE groups. One week after OVX, daily oral administration of PE (0.4 g·kg-1·day·-1) started in PE group, and rats in Sham and OVX groups were given vehicle accordingly. The administrations lasted for 12 weeks. The biological markers including serum osteocalcin (OC) and urinary deoxypyridinoline (DPD) for bone turnover were evaluated at the end of the 12th week. On the 13th week, all the rats were sacrificed. The right proximal tibiae were removed, subjected to micro CT for determination of trabeonlar bone structure and then bone histomorphometry was per- formed to assess bone remodeling. The OVX rats were in a high bone turnover status as evidenced by increased bone formation markers and bone resorption markers. Treatment with PE could suppress the high bone turnover rate in OVX rats. Micro CT data revealed that PE treatment could ameliorate the deterioration of the micro-architecture of proximal tibiae induced by OVX, as demonstrated by greater bone volume, increased trabecular thickness and less trahecular separation in PE group in comparison with OVX group. The static and dynamic parameters of bone histomorphometry indi- cated that there were significant increases in bone formation variables and significant decreases in bone resorption variables between PE and OVX groups. The findings suggest that PE has a beneficial effect on trabecular bone in OVX rat model and this effect is possibly associated with stimulation of bone formation as well as inhibition of bone resorption.

  7. Effect of sodium chloride, chlorite, and perchlorate on the hypochlorite-induced peroxidation of phospholipid liposomes.

    Science.gov (United States)

    Panasenko, O M; Arnhold, J; Sergienko, V I

    1997-01-01

    The abilities of sodium hypochlorite (NaClO), chlorite (NaClO2), chlorate (NaClO3), and perchlorate (NaClO4) to initiate lipid peroxidation (LP) in liposomes formed from unsaturated phosphatidylcholine were compared. It was shown that only NaClO induced an intensive accumulation of LP products (thiobarbituric acid-reactive substances and diene conjugates) in the liposomes as a result of their co-incubation. The other oxochlorates produced no similar effects and did not affect the hypochlorite-induced LP. This indicates that the observed hypochlorite-induced LP does not result from the presence of chlorite, chlorate, or perchlorate anion admixtures in the medium.

  8. Small interfering ribonucleic acid induces liquid-to-ripple phase transformation in a phospholipid membrane

    Science.gov (United States)

    Choubey, Amit; Nomura, Ken-ichi; Kalia, Rajiv K.; Nakano, Aiichiro; Vashishta, Priya

    2014-09-01

    Small interfering ribonucleic acid (siRNA) molecules play a pivotal role in silencing gene expression via the RNA interference mechanism. A key limitation to the widespread implementation of siRNA therapeutics is the difficulty of delivering siRNA-based drugs to cells. Here, we examine changes in the structure and dynamics of a dipalmitoylphosphatidylcholine bilayer in the presence of a siRNA molecule and mechanical barriers to siRNA transfection in the bilayer. Our all-atom molecular dynamics simulation shows that siRNA induces a liquid crystalline-to-ripple phase transformation in the bilayer. The ripple phase consists of a major region of non-interdigitated and a minor region of interdigitated lipid molecules with an intervening kink. In the ripple phase, hydrocarbon chains of lipid molecules have large compressive stresses, which present a considerable barrier to siRNA transfection.

  9. Small interfering ribonucleic acid induces liquid-to-ripple phase transformation in a phospholipid membrane

    Energy Technology Data Exchange (ETDEWEB)

    Choubey, Amit; Nomura, Ken-ichi; Kalia, Rajiv K.; Nakano, Aiichiro; Vashishta, Priya [Collaboratory for Advanced Computing and Simulations, Department of Physics and Astronomy, Department of Computer Science, Department of Chemical Engineering and Materials Science, University of Southern California, Los Angeles, California 90089-0242 (United States)

    2014-09-15

    Small interfering ribonucleic acid (siRNA) molecules play a pivotal role in silencing gene expression via the RNA interference mechanism. A key limitation to the widespread implementation of siRNA therapeutics is the difficulty of delivering siRNA-based drugs to cells. Here, we examine changes in the structure and dynamics of a dipalmitoylphosphatidylcholine bilayer in the presence of a siRNA molecule and mechanical barriers to siRNA transfection in the bilayer. Our all-atom molecular dynamics simulation shows that siRNA induces a liquid crystalline-to-ripple phase transformation in the bilayer. The ripple phase consists of a major region of non-interdigitated and a minor region of interdigitated lipid molecules with an intervening kink. In the ripple phase, hydrocarbon chains of lipid molecules have large compressive stresses, which present a considerable barrier to siRNA transfection.

  10. First description of ABCB4 gene deletions in familial low phospholipid-associated cholelithiasis and oral contraceptives-induced cholestasis

    Science.gov (United States)

    Pasmant, Eric; Goussard, Philippe; Baranes, Laetitia; Laurendeau, Ingrid; Quentin, Samuel; Ponsot, Philippe; Consigny, Yann; Farges, Olivier; Condat, Bertrand; Vidaud, Dominique; Vidaud, Michel; Chen, Jian-Min; Parfait, Béatrice

    2012-01-01

    The wide clinical spectrum of the ABCB4 gene (ATP-binding cassette subfamily B member 4) deficiency syndromes in humans includes low phospholipid-associated cholelithiasis (LPAC), intrahepatic cholestasis of pregnancy (ICP), oral contraceptives-induced cholestasis (CIC), and progressive familial intrahepatic cholestasis type 3 (PFIC3). No ABCB4 mutations are found in a significant proportion of patients with these syndromes. In the present study, 102 unrelated adult patients with LPAC (43 patients) or CIC/ICP (59 patients) were screened for ABCB4 mutations using DNA sequencing. Heterozygous ABCB4 point or short insertion/deletion mutations were found in 37% (16/43) of the LPAC patients and in 27% (16/59) of the ICP/CIC patients. High-resolution gene dosage methodologies were used in the 70 negative patients. Here, we describe for the first time ABCB4 partial or complete heterozygous deletions in 7% (3/43) of the LPAC patients, and in 2% (1/59) of the ICP/CIC patients. Our observations urge to systematically test patients with LPAC, ICP/CIC, and also children with PFIC3 for the presence of ABCB4 deletions using molecular tools allowing detection of gross rearrangements. In clinical practice, a comprehensive ABCB4 alteration-screening algorithm will permit the use of ABCB4 genotyping to confirm the diagnosis of LPAC or ICP/CIC, and allow familial testing. An early diagnosis of these biliary diseases may be beneficial because of the preventive effect of ursodeoxycholic acid on biliary complications. Further comparative studies of patients with well-characterized genotypes (including deletions) and phenotypes will help determine whether ABCB4 mutation types influence clinical outcomes. PMID:21989363

  11. PGF2alpha induced differential expression of genes involved in turnover of extracellular matrix in rat decidual cells

    Directory of Open Access Journals (Sweden)

    Callegari Eduardo A

    2005-01-01

    Full Text Available Abstract In the rat, the decidual tissue is an important component for maternal recognition of pregnancy. Decidualization can be induced by either the implantation of the blastocyst or by artificial stimuli. The process of decidua formation or decidualization, is characterized by growth and differentiation of endometrial stromal cells. Prostaglandin F2alpha (PGF2α has been shown to be involved in inhibition of implantation, alteration of embryo development, induction of luteal regression, and the mediation of pregnancy loss induced by microorganism infections. In order to establish a direct role for PGF2α in decidual function, we have evaluated its effects on the expression of an extensive array of genes using primary decidual cell culture. Upon treatment with PGF2α sixty genes were significantly down-regulated whereas only six genes were up-regulated (from a total of 1176 genes studied. Interestingly, the majority of the genes inhibited by PGF2α are either directly or indirectly involved in the turnover of the extracellular matrix (ECM. Genes such as gelatinase A (MMP2, cathepsin L, tissue inhibitor metalloproteinases 2 (TIMP2 and 3 (TIMP3, plasminogen activator inhibitor1 (PAI1, tissue type plasminogen activator (tPA, urokinase plasminogen activator (tPA, endothelin 1, calponin, carboxypeptidase D and calponin acidic were down regulated. The opposite effect was observed for prostromelysin 53 kDa (proMMP3, plasma proteinase I alpha and alpha 1 antiproteinase, all of which were significantly up-regulated by PGF2α. The results strongly suggest that the abortificient role of elevated levels of PGF2α after implantation is due, in large part, to inhibition of genes involved in the normal turnover of the extracellular matrix necessary for decidual formation.

  12. Vegetarian diet-induced increase in linoleic acid in serum phospholipids is associated with improved insulin sensitivity in subjects with type 2 diabetes.

    Science.gov (United States)

    Kahleova, H; Matoulek, M; Bratova, M; Malinska, H; Kazdova, L; Hill, M; Pelikanova, T

    2013-06-17

    Fatty acids are important cellular constituents that may affect many metabolic processes relevant for the development of diabetes and its complications. We showed previously that vegetarian diet leads to greater increase in metabolic clearance rate of glucose (MCR) than conventional hypocaloric diet. The aim of this secondary analysis was to explore the role of changes in fatty acid composition of serum phospholipids in diet- and exercise-induced changes in MCR in subjects with type 2 diabetes (T2D). Subjects with T2D (n=74) were randomly assigned into a vegetarian group (VG, n=37) following vegetarian diet or a control group (CG, n=37) following a conventional diet. Both diets were calorie restricted (-500 kcal day(-1)). Participants were examined at baseline, 12 weeks of diet intervention and 24 weeks (subsequent 12 weeks of diet were combined with aerobic exercise). The fatty acid composition of serum phospholipids was measured by gas liquid chromatography. MCR was measured by hyperinsulinemic isoglycemic clamp. Visceral fat (VF) was measured by magnetic resonance imaging. Linoleic acid (LA; 18:2n6) increased in VG (P=0.04), whereas it decreased in CG (P=0.04) in response to dietary interventions. It did not change significantly after the addition of exercise in either group (group × time Pvegetarian diet might be related to the increased proportion of LA in serum phospholipids.

  13. Training-induced changes in peritendinous type I collagen turnover determined by microdialysis in humans

    DEFF Research Database (Denmark)

    Langberg, Henning; Rosendal, L; Kjaer, M

    2001-01-01

    1. Acute exercise is found to increase collagen type I formation locally in peritendinous connective tissue of the Achilles' tendon in humans, as determined from changes in interstitial concentrations of collagen propeptide (PICP) and a collagen degradation product (ICTP) by the use of microdialy...... in local connective tissue of the peritendinous Achilles' region. Early in the process both synthesis and degradation are elevated, whereas later, the anabolic processes are dominating causing a net synthesis of type I collagen in tendon-related tissue in humans.......1. Acute exercise is found to increase collagen type I formation locally in peritendinous connective tissue of the Achilles' tendon in humans, as determined from changes in interstitial concentrations of collagen propeptide (PICP) and a collagen degradation product (ICTP) by the use...... of microdialysis catheters. However, the local collagen type I turnover response to training is unknown. 2. Nineteen young males were studied before and after 4 and 11 weeks of physical training. Microdialysis catheters with a high molecular mass cut-off value (3000 kDa), allowing the determination of PICP...

  14. Glucose turnover and hormonal changes during insulin-induced hypoglycemia in trained humans

    DEFF Research Database (Denmark)

    Kjær, Michael; Mikines, K J; Christensen, N J

    1984-01-01

    Eight athletes (T), studied the third morning after the last exercise session, and seven sedentary males (C) (maximal O2 consumption 65 +/- 4 vs. 49 +/- 4 (SE) ml X kg-1 X min-1, for T and C men, respectively) had insulin infused until plasma glucose, at an insulin level of 1,600 pmol X l-1, was ...... of heart rate, free fatty acid, and glycerol was faster. Responses of norepinephrine, cortisol, C-peptide, and lactate were similar in the two groups. Training radically changes hormonal responses but not glucose kinetics in insulin hypoglycemia.......Eight athletes (T), studied the third morning after the last exercise session, and seven sedentary males (C) (maximal O2 consumption 65 +/- 4 vs. 49 +/- 4 (SE) ml X kg-1 X min-1, for T and C men, respectively) had insulin infused until plasma glucose, at an insulin level of 1,600 pmol X l-1, was 1.......9 mmol X l-1. Glucose turnover was determined by primed constant rate infusion of 3-[3H]glucose. Basal C-peptide (0.46 +/- 0.04 vs. 0.73 +/- 0.06 pmol X ml-1) and glucagon (4 +/- 0.4 vs. 10 +/- 2 pmol X l-1) were lower (P less than 0.05) and epinephrine higher (0.30 +/- 0.06 vs. 0.09 +/- 0.03 nmol X l-1...

  15. Mammary cell turnover and expression of lipogenic genes in response to silage induced CLA and diet energy density in lactating cows

    DEFF Research Database (Denmark)

    Nørgaard, J V; Baumgard, L H; Nielsen, T Skau

    2008-01-01

    The objective of this experiment was to investigate possible effects of silage induced differences in milk conjugated linoleic acids (CLA) and diet energy density on cell turnover and production capacity in the mammary gland. Cows were given high levels of canola fat and fed either grass or maize...... silage at either a high or a low diet energy density....

  16. Is gastrectomy-induced high turnover of bone with hyperosteoidosis and increase of mineralization a typical osteomalacia?

    Directory of Open Access Journals (Sweden)

    Takashi Ueyama

    Full Text Available Gastrectomy (GX is thought to result in osteomalacia due to deficiencies in Vitamin D and Ca. Using a GX rat model, we showed that GX induced high turnover of bone with hyperosteoidosis, prominent increase of mineralization and increased mRNA expression of both osteoclast-derived tartrate-resistant acid phosphatase 5b and osteocalcin. The increased 1, 25(OH2D3 level and unchanged PTH and calcitonin levels suggested that conventional bone and Ca metabolic pathways were not involved or changed in compensation. Thus, GX-induced bone pathology was different from a typical osteomalacia. Gene expression profiles through microarray analysis and data mining using Ingenuity Pathway Analysis indicated that 612 genes were up-regulated and 1,097 genes were down-regulated in the GX bone. These genes were related functionally to connective tissue development, skeletal and muscular system development and function, Ca signaling and the role of osteoblasts, osteoclasts and chondrocytes. Network analysis indicated 9 genes (Aldehyde dehydrogenase 1 family, member A1; Aquaporin 9; Interleukin 1 receptor accessory protein; Very low density lipoprotein receptor; Periostin, osteoblast specific factor; Aggrecan; Gremlin 1; Angiopoietin-like 4; Wingless-type MMTV integration site family, member 10B were hubs connected with tissue development and immunological diseases. These results suggest that chronic systemic inflammation might underlie the GX-induced pathological changes in bone.

  17. Pegvisomant-induced serum insulin-like growth factor-I normalization in patients with acromegaly returns elevated markers of bone turnover to normal

    DEFF Research Database (Denmark)

    Parkinson, C; Kassem, M; Heickendorff, Lene

    2003-01-01

    Active acromegaly is associated with increased biochemical markers of bone turnover. Pegvisomant is a GH receptor antagonist that normalizes serum IGF-I in 97% of patients with active acromegaly. We evaluated the effects of pegvisomant-induced serum IGF-I normalization on biochemical markers...... of bone and soft tissue turnover, as well as levels of PTH and vitamin D metabolites, in 16 patients (nine males; median age, 52 yr; range, 28-78 yr) with active acromegaly (serum IGF-I at least 30% above upper limit of an age-related reference range). Serum procollagen III amino-terminal propeptide...

  18. High fat diet-induced changes in mouse muscle mitochondrial phospholipids do not impair mitochondrial respiration despite insulin resistance.

    Directory of Open Access Journals (Sweden)

    Joris Hoeks

    Full Text Available BACKGROUND: Type 2 diabetes mellitus and muscle insulin resistance have been associated with reduced capacity of skeletal muscle mitochondria, possibly as a result of increased intake of dietary fat. Here, we examined the hypothesis that a prolonged high-fat diet consumption (HFD increases the saturation of muscle mitochondrial membrane phospholipids causing impaired mitochondrial oxidative capacity and possibly insulin resistance. METHODOLOGY: C57BL/6J mice were fed an 8-week or 20-week low fat diet (10 kcal%; LFD or HFD (45 kcal%. Skeletal muscle mitochondria were isolated and fatty acid (FA composition of skeletal muscle mitochondrial phospholipids was analyzed by thin-layer chromatography followed by GC. High-resolution respirometry was used to assess oxidation of pyruvate and fatty acids by mitochondria. Insulin sensitivity was estimated by HOMA-IR. PRINCIPAL FINDINGS: At 8 weeks, mono-unsaturated FA (16∶1n7, 18∶1n7 and 18∶1n9 were decreased (-4.0%, p<0.001, whereas saturated FA (16∶0 were increased (+3.2%, p<0.001 in phospholipids of HFD vs. LFD mitochondria. Interestingly, 20 weeks of HFD descreased mono-unsaturated FA while n-6 poly-unsaturated FA (18∶2n6, 20∶4n6, 22∶5n6 showed a pronounced increase (+4.0%, p<0.001. Despite increased saturation of muscle mitochondrial phospholipids after the 8-week HFD, mitochondrial oxidation of both pyruvate and fatty acids were similar between LFD and HFD mice. After 20 weeks of HFD, the increase in n-6 poly-unsaturated FA was accompanied by enhanced maximal capacity of the electron transport chain (+49%, p = 0.002 and a tendency for increased ADP-stimulated respiration, but only when fuelled by a lipid-derived substrate. Insulin sensitivity in HFD mice was reduced at both 8 and 20 weeks. CONCLUSIONS/INTERPRETATION: Our findings do not support the concept that prolonged HF feeding leads to increased saturation of skeletal muscle mitochondrial phospholipids resulting in a decrease in

  19. Inhibition by oxytocin of methamphetamine-induced hyperactivity related to dopamine turnover in the mesolimbic region in mice.

    Science.gov (United States)

    Qi, Jia; Yang, Jing-Yu; Song, Ming; Li, Yan; Wang, Fang; Wu, Chun-Fu

    2008-02-01

    Accumulated data have shown the neuroactive properties of oxytocin (OT), a neurohypophyseal neuropeptide, and its capability of reducing the abuse potential of drugs. The present study investigated the effect of OT on methamphetamine (MAP)-induced hyperactivity in mice and its possible mechanism of action. Locomotor activity was measured after administered with MAP using an infrared sensor. High-performance liquid chromatography with electrochemical detection (HPLC-ECD) was used to detect the content of monoamines and their metabolites in the striatum and accumbens and prefrontal cortex in mice after the behavioral test. OT (0.1, 0.5, and 2.5 microg/mouse, i.c.v.) had no effect on locomotor activity in naïve mice, but inhibited, in a dose-dependent manner, the hyperactivity induced by acute administration of MAP. Atosiban (Ato) (2.0 microg/mouse, i.c.v.), the selective inhibitor of OT receptor, attenuated the inhibitory effect of OT on MAP. A marked reduction of the ratios of 3, 4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) to dopamine (DA) was observed in the striatum and accumbens of mice after acute administration of MAP. OT (2.5 microg, i.c.v.) significantly inhibited the reduction of DOPAC/DA and HVA/DA ratios. However, Ato decreased the ratio of DOPAC/DA significantly in mice compared with OT (2.5 microg) in combination with MAP. There was no significant change in serotonin (5-HT) metabolism in mice after a single administration of MAP. These results suggested that OT inhibited the MAP-induced hyperactivity by altering the DA turnover in the mesolimbic region of mice.

  20. The physical chemistry of the enigmatic phospholipid diacylglycerol pyrophosphate.

    Science.gov (United States)

    Strawn, Liza; Babb, Amy; Testerink, Christa; Kooijman, Edgar Eduard

    2012-01-01

    Phosphatidic acid (PA) is a lipid second messenger that is formed transiently in plants in response to different stress conditions, and plays a role in recruiting protein targets, ultimately enabling an adequate response. Intriguingly, this increase in PA concentration in plants is generally followed by an increase in the phospholipid diacylglycerolpyrophosphate (DGPP), via turnover of PA. Although DGPP has been shown to induce stress-related responses in plants, it is unclear to date what its molecular function is and how it exerts its effect. Here, we describe the physicochemical properties, i.e., effective molecular shape and charge, of DGPP. We find that unlike PA, which imparts a negative curvature stress to a (phospho)lipid bilayer, DGPP stabilizes the bilayer phase of phosphatidylethanolamine (PE), similar to the effect of phosphatidylcholine (PC). DGPP thus has zero curvature. The pKa(2) of the phosphomonoester of DGPP is 7.44 ± 0.02 in a PC bilayer, compared to a pKa(2) of 7.9 for PA. Replacement of half of the PC with PE decreases the pKa(2) of DGPP to 6.71 ± 0.02, similar to the behavior previously described for PA and summarized in the electrostatic-hydrogen bond switch model. Implications for the potential function of DGPP in biomembranes are discussed.

  1. The physical chemistry of the enigmatic phospholipid diacylglycerolpyrophosphate

    Directory of Open Access Journals (Sweden)

    Liza eStrawn

    2012-03-01

    Full Text Available Phosphatidic acid (PA is a lipid second messenger that is formed transiently in plants in response to different stress conditions, and plays a role in recruiting protein targets, ultimately enabling an adequate response. Intriguingly, this increase in PA concentration in plants is generally followed by an increase in the phospholipid diacylglycerolpyrophosphate (DGPP, via turnover of PA. Although DGPP has been shown to induce stress-related responses in plants, it is unclear to date what its molecular function is and how it exerts its effect. Here, we describe the physicochemical properties, i.e. effective molecular shape and charge, of DGPP. We find that unlike PA, which imparts a negative curvature stress to a (phospholipid bilayer, DGPP stabilizes the bilayer phase of phosphatidylethanolamine (PE, similar to the effect of phosphatidylcholine (PC. DGPP thus has zero curvature. The pKa2 of the phosphomonoester of DGPP is 7.44 ± 0.02 in a PC bilayer, compared to a pKa2 of 7.9 for PA. Replacement of half of the PC with PE decreases the pKa2 of DGPP to 6.71 ± 0.02, similar to the behavior previously described for PA and summarized in the electrostatic-hydrogen bond switch model. Implications for the potential function of DGPP in biomembranes are discussed.

  2. The relationship between calcium and the metabolism of plasma membrane phospholipids in hemolysis induced by brown spider venom phospholipase-D toxin.

    Science.gov (United States)

    Chaves-Moreira, Daniele; Souza, Fernanda N; Fogaça, Rosalvo T H; Mangili, Oldemir C; Gremski, Waldemiro; Senff-Ribeiro, Andrea; Chaim, Olga M; Veiga, Silvio S

    2011-09-01

    -mediated rather than leak-promoted because the influx was inhibited by L-type calcium channel inhibitors but not by a T-type calcium channel blocker, sodium channel inhibitor or a specific inhibitor of calcium activated potassium channels. Finally, this inhibition of hemolysis following recombinant phospholipase-D treatment occurred in a concentration-dependent manner in the presence of L-type calcium channel blockers such as nifedipine and verapamil. The data provided herein, suggest that the brown spider venom phospholipase-D-induced hemolysis of human erythrocytes is dependent on the metabolism of membrane phospholipids, such as SM and LPC, generating bioactive products that stimulate a calcium influx into red blood cells mediated by the L-type channel.

  3. Tillage-induced short-term soil organic matter turnover and respiration

    Science.gov (United States)

    Fiedler, Sebastian Rainer; Leinweber, Peter; Jurasinski, Gerald; Eckhardt, Kai-Uwe; Glatzel, Stephan

    2016-09-01

    Tillage induces decomposition and mineralisation of soil organic matter (SOM) by the disruption of macroaggregates and may increase soil CO2 efflux by respiration, but these processes are not well understood at the molecular level. We sampled three treatments (mineral fertiliser: MF; biogas digestate: BD; unfertilised control: CL) of a Stagnic Luvisol a few hours before and directly after tillage as well as 4 days later from a harvested maize field in northern Germany and investigated these samples by means of pyrolysis-field ionisation mass spectrometry (Py-FIMS) and hot-water extraction. Before tillage, the Py-FIMS mass spectra revealed differences in relative ion intensities of MF and CL compared to BD most likely attributable to the cattle manure used for the biogas feedstock and to relative enrichments during anaerobic fermentation. After tillage, the CO2 effluxes were increased in all treatments, but this increase was less pronounced in BD. We explain this by restricted availability of readily biodegradable carbon compounds and possibly an inhibitory effect of sterols from digestates. Significant changes in SOM composition were observed following tillage. In particular, lignin decomposition and increased proportions of N-containing compounds were detected in BD. In MF, lipid proportions increased at the expense of ammonia, ammonium, carbohydrates and peptides, indicating enhanced microbial activity. SOM composition in CL was unaffected by tillage. Our analyses provide strong evidence for significant short-term SOM changes due to tillage in fertilised soils.

  4. Leishmania mexicana infection induces IgG to parasite surface glycoinositol phospholipids that can induce IL-10 in mice and humans.

    Directory of Open Access Journals (Sweden)

    Laurence U Buxbaum

    Full Text Available Infection with the intracellular protozoan parasite Leishmania mexicana causes chronic disease in C57BL/6 mice, in which cutaneous lesions persist for many months with high parasite burdens (10(7-10(8 parasites. This chronic disease process requires host IL-10 and FcγRIII. When Leishmania amastigotes are released from cells, surface-bound IgG can induce IL-10 and suppress IL-12 production from macrophages. These changes decrease IFN-γ from T cells and nitric oxide production in infected cells, which are both required for Leishmania control. However, antibodies targets and the kinetics of antibody production are unknown. Several groups have been unsuccessful in identifying amastigote surface proteins that bind IgG. We now show that glycoinositol phospholipids (GIPLs of L. mexicana are recognized by mouse IgG1 by 6 weeks of infection, with a rapid increase between 12 and 16 weeks, consistent with the timing of chronic disease in C57BL/6 mice vs. healing in FcγRIII-deficient mice. A single prominent spot on TLC is recognized by IgG, and the glycolipid is a glycosyl phosphatidylinositol containing a branched mannose structure. We show that the lipid structure of the GIPL (the sn-2 fatty acid is required for antibody recognition. This GIPL is abundant in L. mexicana amastigotes, rare in stationary-phase promastigotes, and absent in L. major, consistent with a role for antibodies to GIPLs in chronic disease. A mouse monoclonal anti-GIPL IgG recognizes GIPLs on the parasite surface, and induces IL-10 from macrophages. The current work also extends this mouse analysis to humans, finding that L. mexicana-infected humans with localized and diffuse cutaneous leishmaniasis have antibodies that recognize GIPLs, can bind to the surface of amastigotes, and can induce IL-10 from human monocytes. Further characterization of the target glycolipids will have important implications for drug and vaccine development and will elucidate the poorly understood role of

  5. Shock-induced poration, cholesterol flip-flop and small interfering RNA transfection in a phospholipid membrane: Multimillion atom, microsecond molecular dynamics simulations

    Science.gov (United States)

    Choubey, Amit

    Biological cell membranes provide mechanical stability to cells and understanding their structure, dynamics and mechanics are important biophysics problems. Experiments coupled with computational methods such as molecular dynamics (MD) have provided insight into the physics of membranes. We use long-time and large-scale MD simulations to study the structure, dynamics and mechanical behavior of membranes. We investigate shock-induced collapse of nanobubbles in water using MD simulations based on a reactive force field. We observe a focused jet at the onset of bubble shrinkage and a secondary shock wave upon bubble collapse. The jet length scales linearly with the nanobubble radius, as observed in experiments on micron-to-millimeter size bubbles. Shock induces dramatic structural changes, including an ice-VII-like structural motif at a particle velocity of 1 km/s. The incipient ice VII formation and the calculated Hugoniot curve are in good agreement with experimental results. We also investigate molecular mechanisms of poration in lipid bilayers due to shock-induced collapse of nanobubbles. Our multimillion-atom MD simulations reveal that the jet impact generates shear flow of water on bilayer leaflets and pressure gradients across them. This transiently enhances the bilayer permeability by creating nanopores through which water molecules translocate rapidly across the bilayer. Effects of nanobubble size and temperature on the porosity of lipid bilayers are examined. The second research project focuses on cholesterol (CHOL) dynamics in phospholipid bilayers. Several experimental and computational studies have been performed on lipid bilayers consisting of dipalmitoylphosphatidylcholine (DPPC) and CHOL molecules. CHOL interleaflet transport (flip-flop) plays an important role in interleaflet coupling and determining CHOL flip-flop rate has been elusive. Various studies report that the rate ranges between milliseconds to seconds. We calculate CHOL flip-flop rates by

  6. Development of quercetin-phospholipid complex to improve the bioavailability and protection effects against carbon tetrachloride-induced hepatotoxicity in SD rats.

    Science.gov (United States)

    Zhang, Kexia; Zhang, Meiyu; Liu, Ziying; Zhang, Yuanyuan; Gu, Liqiang; Hu, Gaosheng; Chen, Xiaohui; Jia, Jingming

    2016-09-01

    Quercetin (QT) is a natural flavonoid with various biological activities and pharmacological actions. However, the bioavailability of QT is relatively low due to its low solubility which severely limits its use. In this study, we intended to improve the bioavailability of QT by preparing quercetin-phospholipid complex (QT-PC) and investigate the protective effect of QT-PC against carbon tetrachloride (CCl4) induced acute liver damage in Sprague-Dawley (SD) rats. The physicochemical properties of QT-PC were characterized in terms of infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), powder X-ray diffraction (XRPD) and water/n-octanol solubility. FTIR, DSC and XRPD data confirmed the formation of QT-PC. The water solubility of QT was improved significantly in the prepared complex, indicating its increased hydrophilicity. Oral bioavailability of QT and QT-PC was evaluated in SD rats, and the plasma QT was estimated by HPLC-MS. QT-PC exhibited higher Cmax (1.58±0.11 vs. 0.67±0.08μg/mL), increased AUC0-∞ (8.60±1.25 vs. 2.41±0.51mg/Lh) and t1/2z (7.76±1.09 vs. 4.81±0.87h) when compared to free QT. The greater absorption of QT-PC group suggested the improved bioavailability. Moreover, biochemical changes and histopathological observations revealed that QT-PC provided better protection to rat liver than free QT at the same dose. Thus, phospholipid complexation might be one of the suitable approaches to improve the oral bioavailability of QT and obtain better protective effects against CCl4 induced acute liver damage in SD rats than free QT at the same dose level.

  7. Alterations in phospholipid catabolism in Mycobacterium tuberculosis lysX mutant

    Directory of Open Access Journals (Sweden)

    Erin A Maloney

    2011-02-01

    Full Text Available Mycobacterium tuberculosis lysX mutant, defective for production of lysinylated phosphatidylglycerol (L-PG, is sensitive to cationic antimicrobial peptides, is not proficient for proliferation in mice lungs and exhibits altered membrane potential [1]. In the present study we show that a lysX complement strain expressing lysX from inducible tet promoter is proficient in restoring lysX phenotypes confirming that the observed phenotypes are specific to lysX. To evaluate the correlation between changes in membrane potential and lysX activity, we visualized regions of cardiolipin (CL, one of the abundant phospholipids of mycobacteria, by staining with fluorescent dye 10-N-nonyl-acridine orange (NAO and found that CL is localized as bright spots at septal regions and poles of actively dividing cells, but not in stationary phase cells. lysX mutants were elongated and showed more numerous and brighter CL staining at both midcell and quarter cell septa, compared with wild type, indicating a defect in the cell division process. Evaluation of 14C-acetic acid incorporation into major phospholipids such as CL, phosphatidylethanolamine (PE, phosphatidylinositol and their degradation between lysX mutant and its parent revealed differences in the turnover of PE and PI. Our results favor a hypothesis that alterations in phospholipid metabolism could be contributing to changes in membrane potential, hence the observed phenotype of lysX mutant.

  8. Effect of acute thioacetamide administration on rat brain phospholipid metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Osada, J.; Aylagas, H.; Miro-Obradors, M.J.; Arce, C.; Palacios-Alaiz, E.; Cascales, M. (Tufs Univ., Boston, MA (USA))

    1990-09-01

    Brain phospholipid composition and the ({sup 32}P)orthophosphate incorporation into brain phospholipids of control and rats treated for 3 days with thioacetamide were studied. Brain phospholipid content, phosphatidylcholine, phosphatidylethanolamine, lysolecithin and phosphatidic acid did not show any significant change by the effect of thioacetamide. In contrast, thioacetamide induced a significant decrease in the levels of phosphatidylserine, sphingomyelin, phosphatidylinositol and diphosphatidylglycerol. After 75 minutes of intraperitoneal label injection, specific radioactivity of all the above phospholipids with the exception of phosphatidylethanolamine and phosphatidylcholine significantly increased. After 13 hours of isotope administration the specific radioactivity of almost all studied phospholipid classes was elevated, except for phosphatidic acid, the specific radioactivity of which did not change and for diphosphatidylglycerol which showed a decrease in specific radioactivity. These results suggest that under thioacetamide treatment brain phospholipids undergo metabolic transformations that may contribute to the hepatic encephalopathy induced by thioacetamide.

  9. Laser-induced europium(III) luminescence as a probe of the metal ion mediated association of human prothrombin with phospholipid.

    Science.gov (United States)

    Rhee, M J; Horrocks, W D; Kosow, D P

    1982-09-14

    7F0 leads to 5D0 excitation spectroscopy of Eu(III) has been used to investigate the Eu(III) and phospholipid binding properties of human prothrombin. The results indicate that human prothrombin contains four high-affinity Eu(III) binding sites which are distributed into two classes of binding sites. When 4 equiv of Eu(III) is bound to prothrombin, the prothrombin is capable of binding to phospholipid vesicles. The deuterium isotope effect on the lifetime of the Eu(III)-prothrombin complex and the Eu(III)-prothrombin-phospholipid complex was used to determine the number of water molecules coordinated to the Eu(III). In both complexes, each of the Eu(III)'s coordinated to 2.5 +/- 0.5 water molecules. These results indicate that the binding of the Eu(III)-prothrombin complex to the phospholipid does not require the formation of a prothrombin-Eu(III)-phospholipid bridge.

  10. Circulating biologically active oxidized phospholipids show on-going and increased oxidative stress in older male mice

    Directory of Open Access Journals (Sweden)

    Jinbo Liu

    2013-01-01

    Significance: Oxidatively modified phospholipids are increased in the circulation during common, mild oxidant stresses of aging, or in male compared to female animals. Turnover of these biologically active phospholipids by rapid transport into liver and kidney is unchanged, so circulating levels reflect continuously increased production.

  11. Bryostatin, an activator of the calcium phospholipid-dependent protein kinase, blocks phorbol ester-induced differentiation of human promyelocytic leukemia cells HL-60

    Energy Technology Data Exchange (ETDEWEB)

    Kraft, A.S.; Smith, J.B.; Berkow, R.L.

    1986-03-01

    Phorbol esters bind to and activate a calcium phospholipid-dependent protein kinase (C kinase). Some researchers believe that activation of C kinase is necessary for the induction of phorbol ester biologic effects. The authors' research indicates that bryostatin, a macrocyclic lactone that binds to the phorbol ester receptor in human polymorphonuclear leukocytes, also binds to this receptor in the human promyelocytic leukemia cell line, HL-60. Bryostatin activates partially purified C kinase from HL-60 cells in vitro, and when applied to HL-60 cells in vivo, it decreases measurable cytoplasmic C kinase activity. Unlike the phorbol esters, bryostatin is unable to induce a macrophage-like differentiation of HL-60 cells; however, bryostatin, in a dose-dependent fashion, blocks phorbol ester-induced differentiation of HL-60 cells and, if applied within 48 hr of phorbol esters, halts further differentiation. These results suggest that activation of the C kinase by some agents is not sufficient for induction of HL-60 cell differentiation and imply that some of the biologic effects of phorbol esters may occur through a more complex mechanism than previously thought.

  12. Effect of dietary fat saturation on lipid metabolism, arachidonic acid turnover and peritoneal macrophage oxidative stress in mice

    Directory of Open Access Journals (Sweden)

    L.B. Oliveros

    2004-03-01

    Full Text Available We investigated the effects of a saturated fat diet on lipid metabolism and arachidonic acid (AA turnover in mouse resident peritoneal macrophages. The pro-oxidative effect of this diet was also studied. Female C57BL/6 mice were weaned at 21 days of age and assigned to either the experimental diet containing coconut oil (COCO diet, or the control diet containing soybean oil as fat source (10 mice per group. The fat content of each diet was 15% (w/w. Mice were fed for 6 weeks and then sacrificed. The concentration of total lipids, triglycerides, (LDL + VLDL-cholesterol, thiobarbituric acid-reactive substances (TBARS and reduced glutathione were increased in the plasma of mice fed the COCO diet, without changes in phospholipid or total cholesterol concentrations compared to control. The concentrations of total cholesterol, free and esterified cholesterol, triglycerides, and TBARS were increased in the macrophages of COCO-fed mice, while the content of total phospholipids did not change. The phospholipid composition showed an increase of phosphatidylcholine and a decrease of phosphatidylethanolamine. The [³H]-AA distribution in the phospholipid classes showed an increase in phosphatidylcholine and phosphatidylethanolamine. Incorporation of [³H]-cholesterol into the macrophages of COCO-fed mice and into the cholesterol ester fraction was increased. The COCO diet did not affect [³H]-AA uptake but induced an increase in [³H]-AA release. The COCO diet also enhanced AA mobilization induced by lipopolysaccharide. These results indicate that the COCO diet, high in saturated fatty acids, alters the lipid metabolism and AA turnover of peritoneal macrophages in female mice and also produces a significant degree of oxidative stress.

  13. Effect of Age-Related Cartilage Turnover on Serum C-Telopeptide of Collagen Type II and Osteocalcin Levels in Growing Rabbits with and without Surgically Induced Osteoarthritis

    Directory of Open Access Journals (Sweden)

    Chung-Cheng Huang

    2014-01-01

    Full Text Available This study aims to determine the effect of age-related cartilage turnover on the serum C-telopeptide of type II collagen (CTX-II and osteocalcin (OC levels in growing rabbits with and without surgically induced osteoarthritis. Twenty-four New Zealand male 3-month-old rabbits were randomized into three operated groups (n = 6 per group, with surgically induced osteroarthritis in the right knee; after blood sampling, the knees were harvested following euthanization at 2, 3, and 6 months after surgery and a control group (n = 6, blood samples were obtained monthly between 3 and 15 months. Histomorphologically, the medial femoral condyles, particularly the central parts, harbored the most severe osteoarthritic changes among the operated rabbits. The serum levels of CTX-II and OC decreased in the controls from 3 to 11 months and then remained stable. No significant differences in the serum CTX-II and OC levels between the osteoarthritic rabbits and controls were observed. The osteoarthritic-to-normal ratios (ONRs, the ratios of serum CTX-II or OC levels in osteoarthritic rabbits to those of the controls at same ages enabled an overall assessment of osteoarthritis and age-related cartilage turnover. Elevated CTX-II ONRs were observed in rabbits with mild to advanced osteoarthritis. However, the OC ONRs were unhelpful in assessing osteoarthritic growing rabbits.

  14. Lipidomics investigation of reversal effect of glycyrrhizin (GL) towards lithocholic acid (LCA)-induced alteration of phospholipid profiles.

    Science.gov (United States)

    Han, Jing-Chun; Yu, Jian; Gao, Ya-Jie

    2014-12-01

    Glycyrrhizin (GL), the major ingredient isolated from licorice, exerts multiple pharmacological activities. To elucidate the protective mechanism of GL towards lithocholic acid (LCA)-induced liver toxicity using lipidomics. GL (200 mg/kg) dissolved in corn oil was treated intraperitoneally for 7 d. On the 4th day, 200 mg/kg LCA was used to treat mice (i.p., twice daily) for another 4 d. The protective role of GL towards LCA-induced liver toxicity was investigated through evaluating the liver histology and the activity of alanine transaminase (ALT). The complete lipid profile was employed using UFLC-Triple TOF MS-based lipidomics. Intraperitoneal (i.p.) administration of 200 mg/kg GL can significantly protect LCA-induced liver damage, indicated by alleviated histology alteration and prevention of the ALT elevation. Lipidomics analysis can well separate the control group from LCA-treated group, and three lipid components were major contributors, including LPC 16:0, LPC 18:0, and LPC 18:2. GL treatment can significantly prevent LCA-induced reduction of these three lipid compounds, providing a new explanation for GL's protection mechanism towards LCA-induced liver toxicity. The recent study highlights the importance of lipidomics in elucidating the therapeutic mechanism of herbs.

  15. Human stem cell osteoblastogenesis mediated by novel glycogen synthase kinase 3 inhibitors induces bone formation and a unique bone turnover biomarker profile in rats

    Energy Technology Data Exchange (ETDEWEB)

    Gilmour, Peter S., E-mail: Peter.Gilmour@astrazeneca.com [New Opportunities Innovative Medicines group, AstraZeneca R and D, Alderley Park, Cheshire SK10 4TF (United Kingdom); O' Shea, Patrick J.; Fagura, Malbinder [New Opportunities Innovative Medicines group, AstraZeneca R and D, Alderley Park, Cheshire SK10 4TF (United Kingdom); Pilling, James E. [Discovery Sciences, AstraZeneca R and D, Alderley Park, Cheshire SK10 4TF (United Kingdom); Sanganee, Hitesh [New Opportunities Innovative Medicines group, AstraZeneca R and D, Alderley Park, Cheshire SK10 4TF (United Kingdom); Wada, Hiroki [R and I IMed, AstraZeneca R and D, Molndal (Sweden); Courtney, Paul F. [DMPK, AstraZeneca R and D, Alderley Park, Cheshire SK10 4TF (United Kingdom); Kavanagh, Stefan; Hall, Peter A. [Safety Assessment, AstraZeneca R and D, Alderley Park, Cheshire SK10 4TF (United Kingdom); Escott, K. Jane [New Opportunities Innovative Medicines group, AstraZeneca R and D, Alderley Park, Cheshire SK10 4TF (United Kingdom)

    2013-10-15

    Wnt activation by inhibiting glycogen synthase kinase 3 (GSK-3) causes bone anabolism in rodents making GSK-3 a potential therapeutic target for osteoporotic and osteolytic metastatic bone disease. To understand the wnt pathway related to human disease translation, the ability of 3 potent inhibitors of GSK-3 (AZD2858, AR79, AZ13282107) to 1) drive osteoblast differentiation and mineralisation using human adipose-derived stem cells (hADSC) in vitro; and 2) stimulate rat bone formation in vivo was investigated. Bone anabolism/resorption was determined using clinically relevant serum biomarkers as indicators of bone turnover and bone formation assessed in femurs by histopathology and pQCT/μCT imaging. GSK-3 inhibitors caused β-catenin stabilisation in human and rat mesenchymal stem cells, stimulated hADSC commitment towards osteoblasts and osteogenic mineralisation in vitro. AZD2858 produced time-dependent changes in serum bone turnover biomarkers and increased bone mass over 28 days exposure in rats. After 7 days, AZD2858, AR79 or AZ13282107 exposure increased the bone formation biomarker P1NP, and reduced the resorption biomarker TRAcP-5b, indicating increased bone anabolism and reduced resorption in rats. This biomarker profile was differentiated from anabolic agent PTH{sub 1–34} or the anti-resorptive Alendronate-induced changes. Increased bone formation in cortical and cancellous bone as assessed by femur histopathology supported biomarker changes. 14 day AR79 treatment increased bone mineral density and trabecular thickness, and decreased trabecular number and connectivity assessed by pQCT/μCT. GSK-3 inhibition caused hADSC osteoblastogenesis and mineralisation in vitro. Increased femur bone mass associated with changes in bone turnover biomarkers confirmed in vivo bone formation and indicated uncoupling of bone formation and resorption. - Highlights: • Wnt modulation with 3 novel GSK-3 inhibitors alters bone growth. • Human stem cell osteoblastogenesis

  16. Prenatal stress induces long-term effects in cell turnover in the hippocampus-hypothalamus-pituitary axis in adult male rats.

    Directory of Open Access Journals (Sweden)

    Eva Baquedano

    Full Text Available Subchronic gestational stress leads to permanent modifications in the hippocampus-hypothalamus-pituitary-adrenal axis of offspring probably due to the increase in circulating glucocorticoids known to affect prenatal programming. The aim of this study was to investigate whether cell turnover is affected in the hippocampus-hypothalamus-pituitary axis by subchronic prenatal stress and the intracellular mechanisms involved. Restraint stress was performed in pregnant rats during the last week of gestation (45 minutes; 3 times/day. Only male offspring were used for this study and were sacrificed at 6 months of age. In prenatally stressed adults a decrease in markers of cell death and proliferation was observed in the hippocampus, hypothalamus and pituitary. This was associated with an increase in insulin-like growth factor-I mRNA levels, phosphorylation of CREB and calpastatin levels and inhibition of calpain -2 and caspase -8 activation. Levels of the anti-apoptotic protein Bcl-2 were increased and levels of the pro-apoptotic factor p53 were reduced. In conclusion, prenatal restraint stress induces a long-term decrease in cell turnover in the hippocampus-hypothalamus-pituitary axis that might be at least partly mediated by an autocrine-paracrine IGF-I effect. These changes could condition the response of this axis to future physiological and pathophysiological situations.

  17. Prenatal Stress Induces Long-Term Effects in Cell Turnover in the Hippocampus-Hypothalamus-Pituitary Axis in Adult Male Rats

    Science.gov (United States)

    Baquedano, Eva; García-Cáceres, Cristina; Diz-Chaves, Yolanda; Lagunas, Natalia; Calmarza-Font, Isabel; Azcoitia, Iñigo; Garcia-Segura, Luis M.; Argente, Jesús; Chowen, Julie A.; Frago, Laura M.

    2011-01-01

    Subchronic gestational stress leads to permanent modifications in the hippocampus-hypothalamus-pituitary-adrenal axis of offspring probably due to the increase in circulating glucocorticoids known to affect prenatal programming. The aim of this study was to investigate whether cell turnover is affected in the hippocampus-hypothalamus-pituitary axis by subchronic prenatal stress and the intracellular mechanisms involved. Restraint stress was performed in pregnant rats during the last week of gestation (45 minutes; 3 times/day). Only male offspring were used for this study and were sacrificed at 6 months of age. In prenatally stressed adults a decrease in markers of cell death and proliferation was observed in the hippocampus, hypothalamus and pituitary. This was associated with an increase in insulin-like growth factor-I mRNA levels, phosphorylation of CREB and calpastatin levels and inhibition of calpain -2 and caspase -8 activation. Levels of the anti-apoptotic protein Bcl-2 were increased and levels of the pro-apoptotic factor p53 were reduced. In conclusion, prenatal restraint stress induces a long-term decrease in cell turnover in the hippocampus-hypothalamus-pituitary axis that might be at least partly mediated by an autocrine-paracrine IGF-I effect. These changes could condition the response of this axis to future physiological and pathophysiological situations. PMID:22096592

  18. Time pattern of exercise-induced changes in type I collagen turnover after prolonged endurance exercise in humans

    DEFF Research Database (Denmark)

    Langberg, Henning; Skovgaard, D; Asp, S;

    2000-01-01

    Type I collagen is known to adapt to physical activity, and biomarkers of collagen turnover indicate that synthesis can be influenced by a single intense exercise bout, but the exact time pattern of these latter changes are largely undescribed. In the present study, 17 healthy young males had...... indicate that type I collagen synthesis is accelerated in response to prolonged strenuous exercise, reaching a peak after 3 days and returning to preexercising levels 5 days after the completion of a marathon run....... their plasma concentrations of the carboxyterminal propeptide of type I procollagen (PICP), a marker of collagen formation, and the immunoactive carboxyterminal cross-linked telopeptide (ICTP), a marker of collagen resorption, measured before and immediately postexercise, as well as 1, 2, 3, 4, 5, and 6 days...

  19. Role of phospholipids of subunit III in the regulation of structural rearrangements in cytochrome c oxidase of Rhodobacter sphaeroides.

    Science.gov (United States)

    Alnajjar, Khadijeh S; Cvetkov, Teresa; Prochaska, Lawrence

    2015-02-03

    Subunit III of cytochrome c oxidase possesses structural domains that contain conserved phospholipid binding sites. Mutations within these domains induce a loss of phospholipid binding, coinciding with decreased electron transfer activity. Functional and structural roles for phospholipids in the enzyme from Rhodobacter sphaeroides have been investigated. Upon the removal of intrinsic lipids using phospholipase A2, electron transfer activity was decreased 30-50%. Moreover, the delipidated enzyme exhibited turnover-induced, suicide inactivation, which was reversed by the addition of exogenous lipids, most specifically by cardiolipin. Cardiolipin exhibited two sites of interaction with the delipidated enzyme, a high-affinity site (Km = 0.14 μM) and a low-affinity site (Km = 26 μM). Subunit I of the delipidated enzyme exhibited a faster digestion rate when it was treated with α-chymotrypsin compared to that of the wild-type enzyme, suggesting that lipid removal induces a conformational change to expose the digestion sites further. Upon reaction of subunit III of the enzyme with a fluorophore (AEDANS), fluorescence anisotropy showed an increased rotational rate of the fluorophore in the absence of lipids, indicating increased flexibility of subunit III within the enzyme's tertiary structure. Additionally, Förster resonance energy transfer between AEDANS and a fluorescently labeled cardiolipin revealed that cardiolipin binds in the v-shaped cleft of subunit III in the delipidated enzyme and that it moves closer to the active site in subunit I upon a change in the redox state of the enzyme. In conclusion, these results show that the phospholipids regulate events occurring during electron transfer activity by maintaining the structural integrity of the enzyme at the active site.

  20. The aminosterol antibiotic squalamine permeabilizes large unilamellar phospholipid vesicles.

    Science.gov (United States)

    Selinsky, B S; Zhou, Z; Fojtik, K G; Jones, S R; Dollahon, N R; Shinnar, A E

    1998-03-13

    The ability of the shark antimicrobial aminosterol squalamine to induce the leakage of polar fluorescent dyes from large unilamellar phospholipid vesicles (LUVs) has been measured. Micromolar squalamine causes leakage of carboxyfluorescein (CF) from vesicles prepared from the anionic phospholipids phosphatidylglycerol (PG), phosphatidylserine (PS), and cardiolipin. Binding analyses based on the leakage data show that squalamine has its highest affinity to phosphatidylglycerol membranes, followed by phosphatidylserine and cardiolipin membranes. Squalamine will also induce the leakage of CF from phosphatidylcholine (PC) LUVs at low phospholipid concentrations. At high phospholipid concentrations, the leakage of CF from PC LUVs deviates from a simple dose-response relationship, and it appears that some of the squalamine can no longer cause leakage. Fluorescent dye leakage generated by squalamine is graded, suggesting the formation of a discrete membrane pore rather than a generalized disruption of vesicular membranes. By using fluorescently labeled dextrans of different molecular weight, material with molecular weight squalamine, but material with molecular weight >/=10,000 is retained. Negative stain electron microscopy of squalamine-treated LUVs shows that squalamine decreases the average vesicular size in a concentration-dependent manner. Squalamine decreases the size of vesicles containing anionic phospholipid at a lower squalamine/lipid molar ratio than pure PC LUVs. In a centrifugation assay, squalamine solubilizes phospholipid, but only at significantly higher squalamine/phospholipid ratios than required for either dye leakage or vesicle size reduction. Squalamine solubilizes PC at lower squalamine/phospholipid ratios than PG. We suggest that squalamine complexes with phospholipid to form a discrete structure within the bilayers of LUVs, resulting in the transient leakage of small encapsulated molecules. At higher squalamine/phospholipid ratios, these

  1. Pegvisomant-induced serum insulin-like growth factor-I normalization in patients with acromegaly returns elevated markers of bone turnover to normal

    DEFF Research Database (Denmark)

    Parkinson, C; Kassem, M; Heickendorff, Lene

    2003-01-01

    cross-linked N-telopeptide/creatinine ratio, and urinary calcium (24 h collection) were measured (single-batch analysis) at study entry and after IGF-I normalization, along with sera from 32 age- and sex-matched controls. Compared with controls, PIIINP, OC, and CTx were significantly elevated......Active acromegaly is associated with increased biochemical markers of bone turnover. Pegvisomant is a GH receptor antagonist that normalizes serum IGF-I in 97% of patients with active acromegaly. We evaluated the effects of pegvisomant-induced serum IGF-I normalization on biochemical markers...... (PIIINP) and type I procollagen amino-terminal propeptide, osteocalcin (OC), bone-related alkaline phosphatase, C-terminal cross-linked telopeptide of type I collagen (CTx), albumin-corrected calcium, intact PTH, 25-hydroxy vitamin D, 1,25-dihydroxy vitamin D [1,25-(OH)(2) vit D], urinary type 1 collagen...

  2. Altered synaptic phospholipid signaling in PRG-1 deficient mice induces exploratory behavior and motor hyperactivity resembling psychiatric disorders.

    Science.gov (United States)

    Schneider, Patrick; Petzold, Sandra; Sommer, Angela; Nitsch, Robert; Schwegler, Herbert; Vogt, Johannes; Roskoden, Thomas

    2017-08-24

    Plasticity related gene 1 (PRG-1) is a neuron specific membrane protein located at the postsynaptic density of glutamatergic synapses. PRG-1 modulates signaling pathways of phosphorylated lipid substrates such as lysophosphatidic acid (LPA). Deletion of PRG-1 increases presynaptic glutamate release probability leading to neuronal over-excitation. However, due to its cortical expression, PRG-1 deficiency leading to increased glutamatergic transmission is supposed to also affect motor pathways. We therefore analyzed the effects of PRG-1 function on exploratory and motor behavior using homozygous PRG-1 knockout (PRG-1(-/-)) mice and PRG-1/LPA2-receptor double knockout (PRG-1(-/-)/LPA2(-/-)) mice in two open field settings of different size and assessing motor behavior in the Rota Rod test. PRG-1(-/-) mice displayed significantly longer path lengths and higher running speed in both open field conditions. In addition, PRG-1(-/-) mice spent significantly longer time in the larger open field and displayed rearing and self-grooming behavior. Furthermore PRG-1(-/-) mice displayed stereotypical behavior resembling phenotypes of psychiatric disorders in the smaller sized open field arena. Altogether, this behavior is similar to the stereotypical behavior observed in animal models for psychiatric disease of autistic spectrum disorders which reflects a disrupted balance between glutamatergic and GABAergic synapses. These differences indicate an altered excitation/inhibition balance in neuronal circuits in PRG-1(-/-) mice as recently shown in the somatosensory cortex [38]. In contrast, PRG-1(-/-)/LPA2(-/-) did not show significant changes in behavior in the open field suggesting that these specific alterations were abolished when the LPA2-receptor was lacking. Our findings indicate that PRG-1 deficiency led to over-excitability caused by an altered LPA/LPA2-R signaling inducing a behavioral phenotype typically observed in animal models for psychiatric disorders. Copyright

  3. Nature of the charged headgroup determines the fusogenic potential and membrane properties of lithocholic acid phospholipids.

    Science.gov (United States)

    Bhargava, Priyanshu; Singh, Manish; Sreekanth, Vedagopuram; Bajaj, Avinash

    2014-08-07

    Phospholipids play a crucial role in many cellular processes ranging from selective membrane permeability, to membrane fission and fusion, to cellular signaling. Headgroups of phospholipids determine the membrane properties and fusogenicity of these lipids with target cell membranes. We studied the fusogenic and membrane properties of phospholipids possessing unnatural charged headgroups with model membranes using laurdan based membrane hydration studies, DPH based membrane fluidity, and differential scanning calorimetry. We unravel that fusogenicity, membrane hydration, and fluidity of membranes are strongly contingent on the nature of the phospholipid charged headgroup. Our studies unraveled that introduction of bulky headgroups like dimethylamino pyridine induces maximum membrane hydration and perturbations with high fusogenicity as compared to small headgroup based phospholipids. These phospholipids also have the capability of high retention in DPPC membranes. Hydration and fluidity of these phospholipid-doped DPPC membranes are contingent on the nature of the charged headgroup. This study would help in future design of phospholipid based nanomaterials for effective drug delivery.

  4. D1 protein turnover is involved in protection of Photosystem II against UV-B induced damage in the cyanobacterium Arthrospira (Spirulina) platensis.

    Science.gov (United States)

    Wu, Hongyan; Abasova, Leyla; Cheregi, Otilia; Deák, Zsuzsanna; Gao, Kunshan; Vass, Imre

    2011-01-01

    By using two strains of Arthrospira (Spirulina)platensis, an economically important filamentous cyanobacterium, we compared the impairment of PSII activity and loss of D1 protein content under UV-B radiation. Our study showed that UV-B radiation induced a gradual loss of the oxygen-evolving activity to about 56% after 180 min UV-B irradiation both in strains 439 and D-0083, which have been kept under indoor and an outdoor culturing conditions, respectively for a prolonged period of time. The loss of oxygen evolution was accelerated in both strains in the presence of lincomycin, an inhibitor of protein synthesis, and the amount of D1 protein showed a decrease comparable to that of oxygen evolution during the UV-B exposure. However, the UV-B induced loss of oxygen-evolving activity and D1 protein amount was largely prevented when A. platensis cells were exposed to UV-B irradiance supplemented with visible light. Comparison of the two strains also showed a smaller extent of D1 protein synthesis dependent PSII repair in the indoor strain. Our results show that turnover of the D1 protein is an important defense mechanism to counteract the UV-B induced damage of PSII in A. platensis, and also that visible light plays an important role in maintaining the function of PSII under simultaneous exposure to UV-B and visible light.

  5. Screening for the drug-phospholipid interaction: correlation to phospholipidosis

    DEFF Research Database (Denmark)

    Alakoskela, Juha-Matti; Vitovic, Pavol; Kinnunen, Paavo K J

    2009-01-01

    Phospholipid bilayers represent a complex, anisotropic environment fundamentally different from bulk oil or octanol, for instance. Even "simple" drug association to phospholipid bilayers can only be fully understood if the slab-of-hydrocarbon approach is abandoned and the complex, anisotropic pro...... of these interactions in PLD in particular. We also focus on a potential causal connection between drug-induced PLD and steatohepatitis, which is induced by some cationic amphiphilic drugs....

  6. 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) induce hepatic expression of the phospholipid translocase mdr2 in rats

    NARCIS (Netherlands)

    Hooiveld, GJEJ; Vos, TA; Scheffer, GL; Van Goor, H; Bloks, Vincent; Loot, AE; Meijer, DKF; Jansen, PLM; Kuipers, F; Muller, M

    1999-01-01

    Background & Aims: Biliary cholesterol secretion is coupled to that of phospholipids in a process controlled by mdr2 P-glycoprotein activity and bile salt secretion. Statins, the 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, have been shown to affect hepatobiliary lipid secre

  7. Different oxidized phospholipid molecules unequally affect bilayer packing.

    Science.gov (United States)

    Megli, Francesco M; Russo, Luciana

    2008-01-01

    The aim of this study was to gain more detailed knowledge about the effect of the presence of defined oxidized phospholipid molecules in phospholipid bilayers. After chromatographic and mass spectrometry analysis, the previously used product of the Fenton reaction with unsaturated lecithins proved to consist of a plethora of oxidatively modified lecithins, useless either for the detailed study of the effects brought about in the bilayer or as the source of defined oxidized phospholipid molecules. The latter, particularly 2-(omega-carboxyacyl)- and 2-(n-hydroperoxyacyl)-lecithins, can be more conveniently prepared by chemical or enzymatic synthesis rather than by chemical or physical oxidation. The effect of those molecules and of commercially available 12-hydroxy-stearic and dodecanedioic acid was studied in planar supported phospholipid bilayers (SPBs) by use of EPR spectrometry. The SPBs also contained 2-(5-doxylstearoyl)-lecithin as the spin probe, and the EPR spectral anisotropy loss, indicative of bilayer disordering, was measured as a function of the molar percentage of oxidized lipid. Most oxidized lipid molecules examined in this study were able to induce bilayer disordering, while hydroperoxyl group-bearing acyl chains appeared to be much less effective. It is concluded that the effects of different oxidized phospholipids on phospholipid bilayer structure cannot be generalized, as happens with batch-oxidized phospholipids, and that the use of defined oxidized phospholipid molecular species for membrane oxidative stress guarantees a more reliable and detailed response.

  8. Phospholipids and sports performance

    Directory of Open Access Journals (Sweden)

    Purpura Martin

    2007-07-01

    Full Text Available Abstract Phospholipids are essential components of all biological membranes. Phosphatidylcholine (PC and Phosphatidylserine (PS are Phosphatidyl-phospholipids that are required for normal cellular structure and function. The participation in physical activity often challenges a variety of physiological systems; consequently, the ability to maintain normal cellular function during activity can determine sporting performance. The participation in prolonged intense exercise has been shown to reduce circulatory choline concentrations in some individuals. As choline is a pre-cursor to the neurotransmitter Acetylcholine, this finding has encouraged researchers to investigate the hypothesis that supplementation with PC (or choline salts could enhance sporting performance. Although the available data that evaluates the effects of PC supplementation on performance are equivocal, acute oral supplementation with PC (~0.2 g PC per kg body mass has been demonstrated to improve performance in a variety of sporting activities where exercise has depleted circulatory choline concentrations. Short term oral supplementation with soy-derived PS (S-PS has been reported to attenuate circulating cortisol concentrations, improve perceived well-being, and reduce perceived muscle soreness after exercise. More recently, short term oral supplementation (750 mg per day of S-PS for 10 days has been demonstrated to improve exercise capacity during high intensity cycling and tended to increase performance during intermittent running. Although more research is warranted to determine minimum dietary Phospholipid requirements for optimal sporting performance, these findings suggest that some participants might benefit from dietary interventions that increase the intakes of PC and PS.

  9. Analyzing Plant Signaling Phospholipids Through (32)P i-Labeling and TLC

    NARCIS (Netherlands)

    Munnik, T.; Zarza, X.

    2013-01-01

    Lipidomic analyses through LC-, GC-, and ESI-MS/MS can detect numerous lipid species based on headgroup and fatty acid compositions but usually miss the minor phospholipids involved in cell signaling because of their low chemical abundancy. Due to their high turnover, these signaling lipids are,

  10. Egg yolk phospholipids enriched with 1-O-octadecyl-2-oleoyl-sn-glycero-3-phospho-(N-palmitoyl) ethanolamine inhibit development of experimentally induced tumours.

    Science.gov (United States)

    Karafiát, V; Veselý, P; Dvořák, M

    2014-01-01

    Dietary phospholipids (PLs) and their derivatives have proved active in suppression of various health problems and conditions including cancer. In this work we compared the effect of dietary phospholipids from hen egg yolk enriched with N-acyl ether-phosphatidyl ethanolamine (NAEPE) termed bioactive phospholipids (BAP+ preparation) with PLs lacking NAEPE (BAP- preparation) on the growth of transformed cells in vitro and on the promotion and progression of experimental tumours in vivo. For the in vivo experiments we used the chicken model in which liver, lung, and kidney tumours arose via natural selection from single cells initiated by experimentally introduced somatic mutations caused by insertional mutagenesis. Mutagenized animals were fed BAP+ or BAP- diet in various regimens. We observed that BAP+ at low concentrations killed cells of various tumour cell lines in culture but did not compromise viability of non-transformed cells. Oral administration of the BAP+ preparation efficiently reduced progression of all tumour types. However, it did not significantly reduce the number of already initiated tumours and their growth when BAP+ was discontinued. Our data suggest that NAEPE combined with hen egg PLs significantly interferes with tumour progression, possibly through the inhibition of tumour cell viability.

  11. Neutral phospholipids stimulate Na,K-ATPase activity: a specific lipid-protein interaction.

    Science.gov (United States)

    Haviv, Haim; Habeck, Michael; Kanai, Ryuta; Toyoshima, Chikashi; Karlish, Steven J D

    2013-04-05

    Membrane proteins interact with phospholipids either via an annular layer surrounding the transmembrane segments or by specific lipid-protein interactions. Although specifically bound phospholipids are observed in many crystal structures of membrane proteins, their roles are not well understood. Na,K-ATPase is highly dependent on acid phospholipids, especially phosphatidylserine, and previous work on purified detergent-soluble recombinant Na,K-ATPase showed that phosphatidylserine stabilizes and specifically interacts with the protein. Most recently the phosphatidylserine binding site has been located between transmembrane segments of αTM8-10 and the FXYD protein. This paper describes stimulation of Na,K-ATPase activity of the purified human α1β1 or α1β1FXYD1 complexes by neutral phospholipids, phosphatidylcholine, or phosphatidylethanolamine. In the presence of phosphatidylserine, soy phosphatidylcholine increases the Na,K-ATPase turnover rate from 5483 ± 144 to 7552 ± 105 (p phospholipids shows that the stimulatory effect is structurally selective for neutral phospholipids with polyunsaturated fatty acyl chains, especially dilinoleoyl phosphatidylcholine or phosphatidylethanolamine. By contrast to phosphatidylserine, phosphatidylcholine or phosphatidylethanolamine destabilizes the Na,K-ATPase. Structural selectivity for stimulation of Na,K-ATPase activity and destabilization by neutral phospholipids distinguish these effects from the stabilizing effects of phosphatidylserine and imply that the phospholipids bind at distinct sites. A re-examination of electron densities of shark Na,K-ATPase is consistent with two bound phospholipids located between transmembrane segments αTM8-10 and TMFXYD (site A) and between TM2, -4, -6, -and 9 (site B). Comparison of the phospholipid binding pockets in E2 and E1 conformations suggests a possible mechanism of stimulation of Na,K-ATPase activity by the neutral phospholipid.

  12. Several RNase T2 enzymes function in induced tRNA and rRNA turnover in the ciliate Tetrahymena

    DEFF Research Database (Denmark)

    Andersen, Kasper Langebjerg; Collins, Kathleen

    2012-01-01

    RNase T2 enzymes are produced by a wide range of organisms and have been implicated to function in diverse cellular processes, including stress-induced anticodon loop cleavage of mature tRNAs to generate tRNA halves. Here we describe a family of eight RNase T2 genes (RNT2A-RNT2H) in the ciliate...... Tetrahymena thermophila. We constructed strains lacking individual or combinations of these RNT2 genes that were viable but had distinct cellular and molecular phenotypes. In strains lacking only one Rnt2 protein or lacking a subfamily of three catalytically inactive Rnt2 proteins, starvation-induced tRNA...... fragments continued to accumulate, with only a minor change in fragment profile in one strain. We therefore generated strains lacking pairwise combinations of the top three candidates for Rnt2 tRNases. Each of these strains showed a distinct starvation-specific profile of tRNA and rRNA fragment accumulation...

  13. Phospholipidic Monolayers on Formamide

    Science.gov (United States)

    Graner, François; Perez-Oyarzun, Santiago; Saint-Jalmes, Arnaud; Flament, Cyrille; Gallet, François

    1995-02-01

    We report the first phase diagram of a Langmuir film at the air-formamide interface. Stable films of phospholipids such as DPPC or DSPC undergo phase transitions observed on isotherms or by fluorescence microscopy. They display bidimensional gas, liquid and solid phases, as well as two mesophases; the latter coexist with liquid on a sharp first-order transition plateau. We compare these observations with known results on films on water. Nous présentons le premier diagramme de phase d'un film de Langmuir à l'interface air-formamide. On observe, sur des isothermes et par microscopie de fluorescence, des transitions de phase dans des films stables de phospholipides comme le DPPC ou le DSPC. Cinq phases bidimensionnelles sont mises en évidence : gaz, liquide, solide, ainsi que deux mésophases ; ces deux dernières coexistent avec le liquide sur un plateau très marqué de transition du premier ordre. Nous comparons ces observations avec les résultats connus pour les films sur l'eau.

  14. Measurement of a MMP-2 degraded Titin fragment in serum reflects changes in muscle turnover induced by atrophy

    DEFF Research Database (Denmark)

    Sun, S; Henriksen, K; Karsdal, M A;

    2014-01-01

    used to assess biological and clinical relevance. RESULTS: A technically robust ELISA measuring the Titin fragment was developed against a Titin peptide fragment identified in human urine. The fragment was shown to be produced primarily by MMP-2 cleavage of Titin. In the rat muscle DEX induced atrophy...... model, Titin-MMP2 fragment was decreased in the beginning of DEX treatment, and then significantly increased later on during DEX administration. In the human bed rest study, the Titin-MMP2 fragment was initially decreased 11.9 (±3.7) % after 1day of bed rest, and then gradually increased ending up...... at a 16.4 (±4.6) % increase at day 47. CONCLUSIONS: We developed a robust ELISA measuring a muscle derived MMP-2 generated Titin degradation fragment in rat and human serum. Importantly, the fragment can be measured in serum and that these levels are related to induction of skeletal muscle atrophy....

  15. Synthesis of Photoactivatable Phospholipidic Probes

    Institute of Scientific and Technical Information of China (English)

    Qing PENG; Fan Qi QU; Yi XIA; Jie Hua ZHOU; Qiong You WU; Ling PENG

    2005-01-01

    We synthesized and characterized photoactivatable phospholipidic probes 1-3. These probes have the perfluorinated aryl azide function at the polar head of phospholipid. They are stable in dark and become highly reactive upon photoirradiation. The preliminary results suggest that they are promising tools to study the topology of membrane proteins and protein-lipid interactions using photolabeling approach.

  16. Bioactive oxidatively truncated phospholipids in inflammation and apoptosis: formation, targets, and inactivation.

    Science.gov (United States)

    McIntyre, Thomas M

    2012-10-01

    This report reviews structurally related phospholipid oxidation products that are biologically active where molecular mechanisms have been defined. Phospholipids containing polyunsaturated fatty acyl residues are chemically or enzymatically oxidized to phospholipid hydroperoxides, which may fragment on either side of the newly introduced peroxy function to form phospholipids with a truncated sn-2 residue. These truncated phospholipids not subject to biologic control of their production and, depending on the sn-2 residue length and structure, can stimulate the plasma membrane receptor for PAF. Alternatively, these chemically formed products can be internalized by a transport system to either stimulate the lipid activated nuclear transcription factor PPARγ or at higher levels interact with mitochondria to initiate the intrinsic apoptotic cascade. Intracellular PAF acetylhydrolases specifically hydrolyze truncated phospholipids, and not undamaged, biosynthetic phospholipids, to protect cells from oxidative death. Truncated phospholipids are also formed within cells where they couple cytokine stimulation to mitochondrial damage and apoptosis. The relevance of intracellular truncated phospholipids is shown by the complete protection from cytokine induced apoptosis by PAF acetylhydrolase expression. This protection shows truncated phospholipids are the actual effectors of cytokine mediated toxicity. This article is part of a Special Issue entitled: Oxidized phospholipids-their properties and interactions with proteins.

  17. Cortical actin networks induce spatio-temporal confinement of phospholipids in the plasma membrane - a minimally invasive investigation by STED-FCS

    Science.gov (United States)

    Andrade, Débora M.; Clausen, Mathias P.; Keller, Jan; Mueller, Veronika; Wu, Congying; Bear, James E.; Hell, Stefan W.; Lagerholm, B. Christoffer; Eggeling, Christian

    2015-06-01

    Important discoveries in the last decades have changed our view of the plasma membrane organisation. Specifically, the cortical cytoskeleton has emerged as a key modulator of the lateral diffusion of membrane proteins. Cytoskeleton-dependent compartmentalised lipid diffusion has been proposed, but this concept remains controversial because this phenomenon has thus far only been observed with artefact-prone probes in combination with a single technique: single particle tracking. In this paper, we report the first direct observation of compartmentalised phospholipid diffusion in the plasma membrane of living cells using a minimally invasive, fluorescent dye labelled lipid analogue. These observations were made using optical STED nanoscopy in combination with fluorescence correlation spectroscopy (STED-FCS), a technique which allows the study of membrane dynamics on a sub-millisecond time-scale and with a spatial resolution of down to 40 nm. Specifically, we find that compartmentalised phospholipid diffusion depends on the cortical actin cytoskeleton, and that this constrained diffusion is directly dependent on the F-actin branching nucleator Arp2/3. These findings provide solid evidence that the Arp2/3-dependent cortical actin cytoskeleton plays a pivotal role in the dynamic organisation of the plasma membrane, potentially regulating fundamental cellular processes.

  18. Alveolar bone grafting in association with polyostotic fibrous dysplasia and bisphosphonate-induced abnormal bone turnover in a bilateral cleft lip and palate patient: a case report.

    Science.gov (United States)

    Kodama, Yasumitsu; Ogose, Akira; Oguri, Yoshimitsu; Ubaidus, Sobhan; Iizuka, Tateyuki; Takagi, Ritsuo

    2012-09-01

    A case is presented of extensive alveolar bone grafting in a patient with bilateral cleft lip and palate and polyostotic fibrous dysplasia. The patient previously underwent bisphosphonate therapy. Because of an abnormal and often decreased bone turnover caused by the fibrous dysplasia and the bisphosphonate therapy, bone grafting in such a patient poses several potential difficulties. In addition, the histomorphometric analysis of the bone grafts showed markedly decreased bone turnover. However, alveolar bone grafting using the iliac crest was performed successfully. Sufficient occlusion was achieved by postoperative low-loading orthodontic treatment.

  19. The role of C/EBPβ phosphorylation in modulating membrane phospholipids repairing in LPS-induced human lung/bronchial epithelial cells.

    Science.gov (United States)

    Shu, Shiyu; Xu, Yan; Xie, Ling; Ouyang, Yufang

    2017-09-20

    Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is a common critical emergency with high mortality in clinical practice. The key mechanism of ALI/ARDS is that the excessive inflammatory response damages the integrity of alveolar and bronchial cell membrane and thus affects their basic function. Phospholipids are the main component of cell membranes. Phospholipase A2 (PLA2), which catalyzes the cleavage of membrane phospholipids, is the most important inflammatory mediator of ALI. However, clara cell secretory protein 1 (CCSP1), an endogenous PLA2 inhibitor can increase the self-defense of membrane phospholipids. Thus, CCSP1 up-regulation and PLA2 inhibition constitutes an effective method for ensuring the stability of membrane phospholipids and for the treatment of ALI/ARDS. In the present study, we developed an in vitro model of ALI via lipopolysaccharide (LPS) stimulation of a human bronchial epithelial cell line, BEAS-2B, and assessed the mRNA and protein levels of CCSP1 and PLA2 in the model cells. The results demonstrated LPS induction inhibited the transcription and protein expression of CCSP1, but only the protein level of membrane associated PLA2 was increased, suggesting that in the in vitro ALI model, abnormally regulated CCSP1 transcription plays a crucial role in the damage of cell membrane. To find out the reason that CCSP1 expression was decreased in the ALI model, we predicted, by means of bioinformatics, putative transcription factors which would bind to CCSP1 promoter, examined their background and expression, and found that a transcription factor, CCAAT/enhancer binding protein β (C/EBP β), was correlated with the transcription of CCSP1 in the in vitro ALI model, and its phosphorylation in the model was decreased. CHIP-PCR and luciferase reporter assay revealed that C/EBP β bound to CCSP1 promoter and facilitated its transcription. Therefore, we conclude that there is a C/EBP β/CCSP1/PLA2 pathway in the in vitro ALI model. The

  20. Cell signalling and phospholipid metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Boss, W.F.

    1990-01-01

    These studies explored whether phosphoinositide (PI) has a role in plants analogous to its role in animal cells. Although no parallel activity of PI in signal transduction was found in plant cells, activity of inositol phospholipid kinase was found to be modulated by light and by cell wall degrading enzymes. These studies indicate a major role for inositol phospholipids in plant growth and development as membrane effectors but not as a source of second messengers.

  1. Relationship between analgesia and turnover of brain biogenic amines.

    Science.gov (United States)

    Bensemana, D; Gascon, A L

    1978-10-01

    The analgesic activity of morphine, delta9THC, and sodium salicylate was studied concomitantly with changes in brainstem and cortex turnover of dopamine (DA), noradrenaline (NA), and serotonin (5HT). The results show that a correlation exists between the presence of analgesia and the increased turnover rates of the three biogenic amines. Morphine and sodium salicylate induced analgesia is accompanied by an increased turnover rate of all three biogenic amines; delta9THC-induced analgesia is accompanied by an increased turnover rate of DA and 5HT only. There is, however, no consistent relationship between the degree of analgesia and the degree of change in the turnover rates. The existence of the endogenous morphine-like substances, endorphines, may explain why morphine analgesia is distinct from that of delta9THC and sodium salicylate. The possible relationship between this morphine-like substance and biogenic amines is discussed.

  2. A diet high in α-linolenic acid and monounsaturated fatty acids attenuates hepatic steatosis and alters hepatic phospholipid fatty acid profile in diet-induced obese rats.

    Science.gov (United States)

    Hanke, Danielle; Zahradka, Peter; Mohankumar, Suresh K; Clark, Jaime L; Taylor, Carla G

    2013-01-01

    This study investigated the efficacy of the plant-based n-3 fatty acid, α-linolenic acid (ALA), a dietary precursor of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), for modulating hepatic steatosis. Rats were fed high fat (55% energy) diets containing high oleic canola oil, canola oil, a canola/flax oil blend (C/F, 3:1), safflower oil, soybean oil, or lard. After 12 weeks, C/F and weight-matched (WM) groups had 20% less liver lipid. Body mass, liver weight, glucose and lipid metabolism, inflammation and molecular markers of fatty acid oxidation, synthesis, desaturation and elongation did not account for this effect. The C/F group had the highest total n-3 and EPA in hepatic phospholipids (PL), as well as one of the highest DHA and lowest arachidonic acid (n-6) concentrations. In conclusion, the C/F diet with the highest content of the plant-based n-3 ALA attenuated hepatic steatosis and altered the hepatic PL fatty acid profile.

  3. Mitochondrial Biogenesis and Turnover

    OpenAIRE

    Diaz, Francisca; Moraes, Carlos T.

    2008-01-01

    Mitochondrial biogenesis is a complex process involving the coordinated expression of mitochondrial and nuclear genes, the import of the products of the latter into the organelle and turnover. The mechanisms associated with these events have been intensively studied in the last twenty years and our understanding of their details is much improved. Mitochondrial biogenesis requires the participation of calcium signaling that activates a series of calcium dependent protein kinases that in turn a...

  4. Interactions of amelogenin with phospholipids.

    Science.gov (United States)

    Lokappa, Sowmya Bekshe; Chandrababu, Karthik Balakrishna; Dutta, Kaushik; Perovic, Iva; Evans, John Spencer; Moradian-Oldak, Janet

    2015-02-01

    Amelogenin protein has the potential to interact with other enamel matrix proteins, mineral, and cell surfaces. We investigated the interactions of recombinant amelogenin rP172 with small unilamellar vesicles as model membranes, toward the goal of understanding the mechanisms of amelogenin-cell interactions during amelogenesis. Dynamic light scattering (DLS), fluorescence spectroscopy, circular dichroism (CD), and nuclear magnetic resonance (NMR) were used. In the presence of phospholipid vesicles, a blue shift in the Trp fluorescence emission maxima of rP172 was observed (∼334 nm) and the Trp residues of rP172 were inaccessible to the aqueous quencher acrylamide. DLS studies indicated complexation of rP172 and phospholipids, although the possibility of fusion of phospholipids following amelogenin addition cannot be ruled out. NMR and CD studies revealed a disorder-order transition of rP172 in a model membrane environment. Strong fluorescence resonance energy transfer from Trp in rP172 to DNS-bound-phospholipid was observed, and fluorescence polarization studies indicated that rP172 interacted with the hydrophobic core region of model membranes. Our data suggest that amelogenin has ability to interact with phospholipids and that such interactions may play key roles in enamel biomineralization as well as reported amelogenin signaling activities.

  5. Oxidative stability of marine phospholipids

    DEFF Research Database (Denmark)

    Lu, Henna Fung Sieng; Nielsen, Nina Skall; Baron, Caroline Pascale

    prepared in the form of emulsions by high pressure homogenizer. Then, the oxidative and hydrolytic stability of phospholipids was investigated by measurement of simple chemical analyses such as Peroxide Value and Free Fatty Acids, and 31PNMR after 32 days storage at 2ºC. The oxidative stability of MPL...

  6. Maternal deprivation induces a rapid decline in circulating leptin levels and sexually dimorphic modifications in hypothalamic trophic factors and cell turnover.

    Science.gov (United States)

    Viveros, María-Paz; Díaz, Francisca; Mateos, Beatriz; Rodríguez, Noé; Chowen, Julie A

    2010-04-01

    Pathological outcomes, including metabolic and endocrine disturbances, of maternal deprivation (MD) in Wistar rats depend on gender and the timing of deprivation during development. We analyzed the effect of MD between postnatal days 9 and 10, a critical period in hypothalamic development, on circulating hormones and local production of trophic factors involved in this process, as well as on markers of cell turnover and maturation. Males and females were studied 12 and 24 h after MD and 12 h (MD36) after returning the dam to her pups. Circulating corticosterone levels were increased and glucose and leptin levels decreased throughout the study in both sexes. Hypothalamic mRNA levels of leptin receptor increased significantly at MD24 in both sexes, normalizing in females at MD36, but not in males. In male rats insulin-like growth factor mRNA levels were significantly decreased at MD24 and brain derived neurotrophic factor mRNA levels decreased at MD12 and MD24, with both trophic factors unaffected in females. In males cell proliferation was significantly decreased at MD36, as were the glial structural proteins, glial fibrillary acidic protein and vimentin. In females, nestin levels decreased significantly at MD24. These results indicate that MD differently affects trophic factors and cell-turnover in the hypothalamus of males and females, which may underlie the sex differences seen in the endocrine and metabolic outcome.

  7. Bacterial phospholipide antigens and their taxonomic significance.

    Science.gov (United States)

    Karalnik, B V; Razbash, M P; Akhmetova, E A

    1981-01-01

    The investigation of interrelationships between the phospholipides of various microorganisms (33 strains of corynebacteria, mycobacteria and staphylococci) using crossed antibody neutralization reactions with phospholipide antigenic erythrocyte diagnostic was used for the assessment of the degree of antigenic propinquity and antigenic differences between the phospholipides of bacteria of the same species, genus, and of different genera. The role of the determinants of the corresponding (their own) and "foreign" genera in the antigenic differences between the phospholipides of the microorganisms investigated was established. On the basis of the results obtained the conclusion has been drawn that the method of assessment of antigenic interrelationships between phospholipides can be used for the study of some taxonomic problems.

  8. Phospholipids in foods: prooxidants or antioxidants?

    Science.gov (United States)

    Cui, Leqi; Decker, Eric A

    2016-01-15

    Lipid oxidation is one of the major causes of quality deterioration in natural and processed foods and thus a large economic concern in the food industry. Phospholipids, especially lecithins, are already widely used as natural emulsifiers and have been gaining increasing interest as natural antioxidants to control lipid oxidation. This review summarizes the fatty acid composition and content of phospholipids naturally occurring in several foods. The role of phospholipids as substrates for lipid oxidation is discussed, with a focus on meats and dairy products. Prooxidant and antioxidant mechanisms of phospholipids are also discussed to get a better understanding of the possible opportunities for using phospholipids as food antioxidants.

  9. Quantification of isotopic turnover in agricultural systems

    Science.gov (United States)

    Braun, A.; Auerswald, K.; Schnyder, H.

    2012-04-01

    additional change in nutrition induces changes in physiology that are likely to bias the estimation of the isotopic turnover. We designed an experiment with lactating cows which were successively exposed to the diet's natural isotopic variation and a diet-switch. We examined whether the same turnover information can be obtained from the natural (uncontrolled, short-term) isotopic variation as from the diet-switch experiment. Statistical methods to retrieve the turnover characteristics comprised multi-pool compartmental modeling for the diet-switch experiment as well as correlation analysis to perform wiggle-matching and quantification of autocorrelation (geostatistics) for the analysis of the natural variation. All three methods yielded similar results but differed in their strengths and weaknesses that will be highlighted. Combining the strengths of the new methods can make this tool even more advantageous than diet-switch experiments in many cases. In particular, the new approach empowers studying isotope turnover under a wider range of keepings, wildlife conditions and species, yielding turnover estimates that are not biased by changes in nutrition.

  10. 13C- and 15N-Labeling Strategies Combined with Mass Spectrometry Comprehensively Quantify Phospholipid Dynamics in C. elegans.

    Directory of Open Access Journals (Sweden)

    Blair C R Dancy

    Full Text Available Membranes define cellular and organelle boundaries, a function that is critical to all living systems. Like other biomolecules, membrane lipids are dynamically maintained, but current methods are extremely limited for monitoring lipid dynamics in living animals. We developed novel strategies in C. elegans combining 13C and 15N stable isotopes with mass spectrometry to directly quantify the replenishment rates of the individual fatty acids and intact phospholipids of the membrane. Using multiple measurements of phospholipid dynamics, we found that the phospholipid pools are replaced rapidly and at rates nearly double the turnover measured for neutral lipid populations. In fact, our analysis shows that the majority of membrane lipids are replaced each day. Furthermore, we found that stearoyl-CoA desaturases (SCDs, critical enzymes in polyunsaturated fatty acid production, play an unexpected role in influencing the overall rates of membrane maintenance as SCD depletion affected the turnover of nearly all membrane lipids. Additionally, the compromised membrane maintenance as defined by LC-MS/MS with SCD RNAi resulted in active phospholipid remodeling that we predict is critical to alleviate the impact of reduced membrane maintenance in these animals. Not only have these combined methodologies identified new facets of the impact of SCDs on the membrane, but they also have great potential to reveal many undiscovered regulators of phospholipid metabolism.

  11. Mitochondrial biogenesis and turnover.

    Science.gov (United States)

    Diaz, Francisca; Moraes, Carlos T

    2008-07-01

    Mitochondrial biogenesis is a complex process involving the coordinated expression of mitochondrial and nuclear genes, the import of the products of the latter into the organelle and turnover. The mechanisms associated with these events have been intensively studied in the last 20 years and our understanding of their details is much improved. Mitochondrial biogenesis requires the participation of calcium signaling that activates a series of calcium-dependent protein kinases that in turn activate transcription factors and coactivators such as PGC-1alpha that regulates the expression of genes coding for mitochondrial components. In addition, mitochondrial biogenesis involves the balance of mitochondrial fission-fusion. Mitochondrial malfunction or defects in any of the many pathways involved in mitochondrial biogenesis can lead to degenerative diseases and possibly play an important part in aging.

  12. How Employee Turnover Affects Productivity

    DEFF Research Database (Denmark)

    Eriksen, Bo

    Research on employee turnover suggests that turnover results in negative organization-level outcomes. This paper provides a firm-level analysis of the impact of the in- and outflows of human resources on productivity and how the presence of organizational slack resources moderates the effects...

  13. Surface Modification of a Titanium Alloy with a Phospholipid Polymer Prepared by a Plasma-Induced Grafting Technique to Improve Surface Thromboresistance

    OpenAIRE

    Ye, Sang Ho; Johnson, Carl A.; Woolley, Joshua R.; Oh, Heung-Il; Gamble, Lara J.; Ishihara, Kazuhiko; Wagner, William R.

    2009-01-01

    To improve the thromboresistance of a titanium alloy (TiAl6V4) surface which is currently utilized in several ventricular assist devices (VADs), a plasma-induced graft polymerization of 2-methacryloyloxyethyl phosphorylcholine (MPC) was carried out and poly(MPC) (PMPC) chains were covalently attached onto a TiAl6V4 surface by a plasma induced technique. Cleaned TiAl6V4 surfaces were pretreated with H2O-vapor-plasma and silanated with 3-methacryloylpropyltrimethoxysilane (MPS). Next, a plasma-...

  14. Short duration small sided football and to a lesser extent whole body vibration exercise induce acute changes in markers of bone turnover

    DEFF Research Database (Denmark)

    Bowtell, Joanna L.; Jackman, Sarah R; Scott, Suzanne

    2016-01-01

    We aimed to study whether short-duration vibration exercise or football sessions of two different durations acutely changed plasma markers of bone turnover and muscle strain. Inactive premenopausal women (n = 56) were randomized to complete a single bout of short (FG15) or long duration (FG60......) small sided football or low magnitude whole body vibration training (VIB). Procollagen type 1 amino-terminal propeptide (P1NP) was increased during exercise for FG15 (51.6 ± 23.0 to 56.5 ± 22.5 μg·L(-1), mean ± SD, P ... in response to a single session of vibration exercise, both short and longer durations of small sided football acutely increased plasma P1NP, osteocalcin, and creatine kinase. This may contribute to favorable effects of chronic training on musculoskeletal health....

  15. Mammalian P4-ATPases and ABC transporters and their role in phospholipid transport.

    Science.gov (United States)

    Coleman, Jonathan A; Quazi, Faraz; Molday, Robert S

    2013-03-01

    Transport of phospholipids across cell membranes plays a key role in a wide variety of biological processes. These include membrane biosynthesis, generation and maintenance of membrane asymmetry, cell and organelle shape determination, phagocytosis, vesicle trafficking, blood coagulation, lipid homeostasis, regulation of membrane protein function, apoptosis, etc. P(4)-ATPases and ATP binding cassette (ABC) transporters are the two principal classes of membrane proteins that actively transport phospholipids across cellular membranes. P(4)-ATPases utilize the energy from ATP hydrolysis to flip aminophospholipids from the exocytoplasmic (extracellular/lumen) to the cytoplasmic leaflet of cell membranes generating membrane lipid asymmetry and lipid imbalance which can induce membrane curvature. Many ABC transporters play crucial roles in lipid homeostasis by actively transporting phospholipids from the cytoplasmic to the exocytoplasmic leaflet of cell membranes or exporting phospholipids to protein acceptors or micelles. Recent studies indicate that some ABC proteins can also transport phospholipids in the opposite direction. The importance of P(4)-ATPases and ABC transporters is evident from the findings that mutations in many of these transporters are responsible for severe human genetic diseases linked to defective phospholipid transport. This article is part of a Special Issue entitled Phospholipids and Phospholipid Metabolism.

  16. How Employee Turnover Affects Productivity

    DEFF Research Database (Denmark)

    Eriksen, Bo

    Research on employee turnover suggests that turnover results in negative organization-level outcomes. This paper provides a firm-level analysis of the impact of the in- and outflows of human resources on productivity and how the presence of organizational slack resources moderates the effects...... of employee turnover. Drawing on a unique longitudinal dataset of 2,926 Danish manufacturing firms that combine individual-level data with firm-level data, the paper shows that job turnover has a substantial negative effect on total productivity but that the firm’s size, its capital intensity, and its age...... moderate this effect so that the negative consequences of employee turnover are less severe for larger, older and capital intensive firms. These moderating variables indicate the presence of slack resources in the firm, and thus that the accumulation of slack reduces the efficiency losses from employee...

  17. How Employee Turnover Affects Productivity

    DEFF Research Database (Denmark)

    Eriksen, Bo

    Research on employee turnover suggests that turnover results in negative organization-level outcomes. This paper provides a firm-level analysis of the impact of the in- and outflows of human resources on productivity and how the presence of organizational slack resources moderates the effects...... of employee turnover. Drawing on a unique longitudinal dataset of 2,926 Danish manufacturing firms that combine individual-level data with firm-level data, the paper shows that job turnover has a substantial negative effect on total productivity but that the firm’s size, its capital intensity, and its age...... moderate this effect so that the negative consequences of employee turnover are less severe for larger, older and capital intensive firms. These moderating variables indicate the presence of slack resources in the firm, and thus that the accumulation of slack reduces the efficiency losses from employee...

  18. Collagen turnover after tibial fractures

    DEFF Research Database (Denmark)

    Joerring, S; Krogsgaard, M; Wilbek, H

    1994-01-01

    Collagen turnover after tibial fractures was examined in 16 patients with fracture of the tibial diaphysis and in 8 patients with fracture in the tibial condyle area by measuring sequential changes in serological markers of turnover of types I and III collagen for up to 26 weeks after fracture...... collagen. A group comparison showed characteristic sequential changes in the turnover of types I and III collagen in fractures of the tibial diaphysis and tibial condyles. The turnover of type III collagen reached a maximum after 2 weeks in both groups. The synthesis of type I collagen reached a maximum...... after 2 weeks in the diaphyseal fractures and after 6 weeks in the condylar fractures. The degradation of type I collagen increased after 4 days and reached a maximum at 2 weeks in both groups. The interindividual variation was wide. On a group basis, the turnover of types I and III collagen had...

  19. Nanomechanics of electrospun phospholipid fiber

    Energy Technology Data Exchange (ETDEWEB)

    Mendes, Ana C., E-mail: anac@food.dtu.dk, E-mail: ioach@food.dtu.dk; Chronakis, Ioannis S., E-mail: anac@food.dtu.dk, E-mail: ioach@food.dtu.dk [Technical University of Denmark, DTU-Food, Søltofts Plads B227, DK-2800, Kgs. Lyngby (Denmark); Nikogeorgos, Nikolaos; Lee, Seunghwan [Department of Mechanical Engineering, Technical University of Denmark, DK-2800 Kgs. Lyngby (Denmark)

    2015-06-01

    Electrospun asolectin phospholipid fibers were prepared using isooctane as a solvent and had an average diameter of 6.1 ± 2.7 μm. Their mechanical properties were evaluated by nanoindentation using Atomic Force Microscopy, and their elastic modulus was found to be approximately 17.2 ± 1 MPa. At a cycle of piezo expansion-retraction (loading-unloading) of a silicon tip on a fiber, relatively high adhesion was observed during unloading. It is proposed that this was primarily due to molecular rearrangements at the utmost layers of the fiber caused by the indentation of the hydrophilic tip. The phospholipid fibers were shown to be stable in ambient conditions, preserving the modulus of elasticity up to 24 h.

  20. [Bile phospholipids; function and significance].

    Science.gov (United States)

    Salvioli, G; Salati, R

    1977-09-19

    The part played by phospholipides in the genesis of cholesterol gallstone considered. This is present in patients who frequently present a lecithin synthesis defect at hepatic level since precursors are used for forming triglycerides. Nevertheless polyunsaturated phosphatidicholine has a negative influence on the SB + PL/C ratio in the bile of T-tube subjects receiving 2 g of substance i.v. for 5 days.

  1. Managing voluntary turnover through challenging assignments

    NARCIS (Netherlands)

    Preenen, P.T.Y.; Pater, I.E. de; Vianen, A.E.M. van; Keijzer, L.

    2011-01-01

    This study examines employees' challenging assignments as manageable means to reduce turnover intentions, job search behaviors, and voluntary turnover. Results indicate that challenging assignments are negatively related to turnover intentions and job search behaviors and that these relationships

  2. Biomass turnover time in terrestrial ecosystems halved by land use

    Science.gov (United States)

    Erb, Karl-Heinz; Fetzel, Tamara; Plutzar, Christoph; Kastner, Thomas; Lauk, Christian; Mayer, Andreas; Niedertscheider, Maria; Körner, Christian; Haberl, Helmut

    2016-09-01

    The terrestrial carbon cycle is not well quantified. Biomass turnover time is a crucial parameter in the global carbon cycle, and contributes to the feedback between the terrestrial carbon cycle and climate. Biomass turnover time varies substantially in time and space, but its determinants are not well known, making predictions of future global carbon cycle dynamics uncertain. Land use--the sum of activities that aim at enhancing terrestrial ecosystem services--alters plant growth and reduces biomass stocks, and is hence expected to affect biomass turnover. Here we explore land-use-induced alterations of biomass turnover at the global scale by comparing the biomass turnover of the actual vegetation with that of a hypothetical vegetation state with no land use under current climate conditions. We find that, in the global average, biomass turnover is 1.9 times faster with land use. This acceleration affects all biomes roughly equally, but with large differences between land-use types. Land conversion, for example from forests to agricultural fields, is responsible for 59% of the acceleration; the use of forests and natural grazing land accounts for 26% and 15% respectively. Reductions in biomass stocks are partly compensated by reductions in net primary productivity. We conclude that land use significantly and systematically affects the fundamental trade-off between carbon turnover and carbon stocks.

  3. Enteropathogenic Escherichia coli infection triggers host phospholipid metabolism perturbations.

    Science.gov (United States)

    Wu, Y; Lau, B; Smith, S; Troyan, K; Barnett Foster, D E

    2004-12-01

    Enteropathogenic Escherichia coli (EPEC) specifically recognizes phosphatidylethanolamine (PE) on the outer leaflet of host epithelial cells. EPEC also induces apoptosis in epithelial cells, which results in increased levels of outer leaflet PE and increased bacterial binding. Consequently, it is of interest to investigate whether EPEC infection perturbs host cell phospholipid metabolism and whether the changes play a role in the apoptotic signaling. Our findings indicate that EPEC infection results in a significant increase in the epithelial cell PE level and a corresponding decrease in the phosphatidylcholine (PC) level. PE synthesis via both the de novo pathway and the serine decarboxylation pathway was enhanced, and de novo synthesis of phosphatidylcholine via CDP-choline was reduced. The changes were transitory, and the maximum change was noted after 4 to 5 h of infection. Addition of exogenous PC or CDP-choline to epithelial cells prior to infection abrogated EPEC-induced apoptosis, suggesting that EPEC infection inhibits the CTP-phosphocholine cytidylyltransferase step in PC synthesis, which is reportedly inhibited during nonmicrobially induced apoptosis. On the other hand, incorporation of exogenous PE by the host cells enhanced EPEC-induced apoptosis and necrosis without increasing bacterial adhesion. This is the first report that pathogen-induced apoptosis is associated with significant changes in PE and PC metabolism, and the results suggest that EPEC adhesion to a host membrane phospholipid plays a role in disruption of host phospholipid metabolism.

  4. An antioxidant-like action for non-peroxidisable phospholipids using ferrous iron as a peroxidation initiator.

    Science.gov (United States)

    Cortie, Colin H; Else, Paul L

    2015-06-01

    The degradation of phospholipids containing polyunsaturated fatty acids, termed peroxidation, poses a constant challenge to membranes lipid composition and function. Phospholipids with saturated (e.g. PC 16:0/16:0) and monounsaturated fatty acids (e.g. PC 16:0/18:1) are some of the most common phospholipids found in membranes and are generally not peroxidisable. The present experiments show that these non-peroxidisable phospholipids, when present in liposomes with peroxidisable phospholipids (i.e. those containing polyunsaturated fatty acids) such as PC 16:0/18:2 and Soy PC, produce an inhibitory effect on rates of peroxidation induced by ferrous-iron. This inhibitory effect acts to extend the duration of the lag phase by several-fold. If present in natural systems, this action could enhance the capacity of conventional antioxidant mechanisms in membranes. The results of this preliminary work suggest that non-peroxidisable phospholipids may exert an antioxidant-like action in membranes.

  5. Surface modification of a titanium alloy with a phospholipid polymer prepared by a plasma-induced grafting technique to improve surface thromboresistance.

    Science.gov (United States)

    Ye, Sang Ho; Johnson, Carl A; Woolley, Joshua R; Oh, Heung-Il; Gamble, Lara J; Ishihara, Kazuhiko; Wagner, William R

    2009-11-01

    To improve the thromboresistance of a titanium alloy (TiAl(6)V(4)) surface which is currently utilized in several ventricular assist devices (VADs), a plasma-induced graft polymerization of 2-methacryloyloxyethyl phosphorylcholine (MPC) was carried out and poly(MPC) (PMPC) chains were covalently attached onto a TiAl(6)V(4) surface by a plasma induced technique. Cleaned TiAl(6)V(4) surfaces were pretreated with H(2)O-vapor-plasma and silanated with 3-methacryloylpropyltrimethoxysilane (MPS). Next, a plasma-induced graft polymerization with MPC was performed after the surfaces were pretreated with Ar plasma. Surface compositions were verified by X-ray photoelectron spectroscopy (XPS). In vitro blood biocompatibility was evaluated by contacting the modified surfaces with ovine blood under continuous mixing. Bulk phase platelet activation was quantified by flow cytometric analysis, and surfaces were observed with scanning electron microscopy after blood contact. XPS data demonstrated successful modification of the TiAl(6)V(4) surfaces with PMPC as evidenced by increased N and P on modified surfaces. Platelet deposition was markedly reduced on the PMPC grafted surfaces and platelet activation in blood that contacted the PMPC-grafted samples was significantly reduced relative to the unmodified TiAl(6)V(4) and polystyrene control surfaces. Durability studies under continuously mixed water suggested no change in surface modification over a 1-month period. This modification strategy shows promise for further investigation as a means to reduce the thromboembolic risk associated with the metallic blood-contacting surfaces of VADs and other cardiovascular devices under development.

  6. 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.

    Science.gov (United States)

    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.

  7. Anticancer effects of saponin and saponin-phospholipid complex of Panax notoginseng grown in Vietnam

    Institute of Scientific and Technical Information of China (English)

    Thu Dang Kim; Hai Nguyen Thanh; Duong Nguyen Thuy; Loi Vu Duc; Thu Vu Thi; Hung Vu Manh; Patcharee Boonsiri; Tung Bui Thanh

    2016-01-01

    Objective: To evaluate the antitumor activity both in vitro and in vivo of saponin–phospholipid complex of Panax notoginseng. Methods: The in vitro cytotoxic effect of saponins extract and saponin–phospholipid complex against human lung cancer NCI-H460 and breast cancer cell lines BT474 was examined using MTS assay. For in vivo evaluation of antitumor potential, saponin and saponin–phospholipid complex were administered orally in rats induced mammary carcinogenesis by 7,12-dimethylbenz(a)anthracene, for 30 days. Results: Our data showed that saponin–phospholipid complex had stronger anticancer effect compared to saponin extract. The IC50 values of saponin–phospholipid complex and saponin extract for NCI-H460 cell lines were 28.47μg/mL and 47.97μg/mL, respectively and these values for BT474 cells were 53.18μg/mL and 86.24μg/mL, respectively. In vivo experiments, administration of saponin, saponin–phospholipid complex and paclitaxel (positive control) effectively suppressed 7,12-dimethylbenz(a) anthracene-induced breast cancer evidenced by a decrease in tumor volume, the reduction of lipid peroxidation level and increase in the body weight, and elevated the enzymatic antioxidant activities of su-peroxide dismutase, catalase, glutathione peroxidase in rat breast tissue. Conclusions: Our study suggests that saponin extract from Panax notoginseng and saponin–phospholipid complex have potential to prevent cancer, especially breast cancer.

  8. Water level changes affect carbon turnover and microbial community composition in lake sediments.

    Science.gov (United States)

    Weise, Lukas; Ulrich, Andreas; Moreano, Matilde; Gessler, Arthur; Kayler, Zachary E; Steger, Kristin; Zeller, Bernd; Rudolph, Kristin; Knezevic-Jaric, Jelena; Premke, Katrin

    2016-05-01

    Due to climate change, many lakes in Europe will be subject to higher variability of hydrological characteristics in their littoral zones. These different hydrological regimes might affect the use of allochthonous and autochthonous carbon sources. We used sandy sediment microcosms to examine the effects of different hydrological regimes (wet, desiccating, and wet-desiccation cycles) on carbon turnover. (13)C-labelled particulate organic carbon was used to trace and estimate carbon uptake into bacterial biomass (via phospholipid fatty acids) and respiration. Microbial community changes were monitored by combining DNA- and RNA-based real-time PCR quantification and terminal restriction fragment length polymorphism (T-RFLP) analysis of 16S rRNA. The shifting hydrological regimes in the sediment primarily caused two linked microbial effects: changes in the use of available organic carbon and community composition changes. Drying sediments yielded the highest CO2 emission rates, whereas hydrological shifts increased the uptake of allochthonous organic carbon for respiration. T-RFLP patterns demonstrated that only the most extreme hydrological changes induced a significant shift in the active and total bacterial communities. As current scenarios of climate change predict an increase of drought events, frequent variations of the hydrological regimes of many lake littoral zones in central Europe are anticipated. Based on the results of our study, this phenomenon may increase the intensity and amplitude in rates of allochthonous organic carbon uptake and CO2 emissions.

  9. Phosphatidate phosphatase regulates membrane phospholipid synthesis via phosphatidylserine synthase.

    Science.gov (United States)

    Carman, George M; Han, Gil-Soo

    2017-08-16

    The yeast Saccharomyces cerevisiae serves as a model eukaryote to elucidate the regulation of lipid metabolism. In exponentially growing yeast, a diverse set of membrane lipids are synthesized from the precursor phosphatidate via the liponucleotide intermediate CDP-diacylglycerol. As cells exhaust nutrients and progress into the stationary phase, phosphatidate is channeled via diacylglycerol to the synthesis of triacylglycerol. The CHO1-encoded phosphatidylserine synthase, which catalyzes the committed step in membrane phospholipid synthesis via CDP-diacylglycerol, and the PAH1-encoded phosphatidate phosphatase, which catalyzes the committed step in triacylglycerol synthesis are regulated throughout cell growth by genetic and biochemical mechanisms to control the balanced synthesis of membrane phospholipids and triacylglycerol. The loss of phosphatidate phosphatase activity (e.g., pah1Δ mutation) increases the level of phosphatidate and its conversion to membrane phospholipids by inducing Cho1 expression and phosphatidylserine synthase activity. The regulation of the CHO1 expression is mediated through the inositol-sensitive upstream activation sequence (UASINO), a cis-acting element for the phosphatidate-controlled Henry (Ino2-Ino4/Opi1) regulatory circuit. Consequently, phosphatidate phosphatase activity regulates phospholipid synthesis through the transcriptional regulation of the phosphatidylserine synthase enzyme. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Anticancer effects of saponin and saponin–phospholipid complex of Panax notoginseng grown in Vietnam

    OpenAIRE

    Thu Dang Kim; Hai Nguyen Thanh; Duong Nguyen Thuy; Loi Vu Duc; Thu Vu Thi; Hung Vu Manh; Patcharee Boonsiri; Tung Bui Thanh

    2016-01-01

    Objective: To evaluate the antitumor activity both in vitro and in vivo of saponin–phospholipid complex of Panax notoginseng. Methods: The in vitro cytotoxic effect of saponins extract and saponin–phospholipid complex against human lung cancer NCI-H460 and breast cancer cell lines BT474 was examined using MTS assay. For in vivo evaluation of antitumor potential, saponin and saponin–phospholipid complex were administered orally in rats induced mammary carcinogenesis by 7,12-dimethylbenz(a)a...

  11. Liposome Model Systems to Study the Endosomal Escape of Cell-Penetrating Peptides: Transport across Phospholipid Membranes Induced by a Proton Gradient

    Directory of Open Access Journals (Sweden)

    Fatemeh Madani

    2011-01-01

    Full Text Available Detergent-mediated reconstitution of bacteriorhodopsin (BR into large unilamellar vesicles (LUVs was investigated, and the effects were carefully characterized for every step of the procedure. LUVs were prepared by the extrusion method, and their size and stability were examined by dynamic light scattering. BR was incorporated into the LUVs using the detergent-mediated reconstitution method and octyl glucoside (OG as detergent. The result of measuring pH outside the LUVs suggested that in the presence of light, BR pumps protons from the outside to the inside of the LUVs, creating acidic pH inside the vesicles. LUVs with 20% negatively charged headgroups were used to model endosomes with BR incorporated into the membrane. The fluorescein-labeled cell-penetrating peptide penetratin was entrapped inside these BR-containing LUVs. The light-induced proton pumping activity of BR has allowed us to observe the translocation of fluorescein-labeled penetratin across the vesicle membrane.

  12. Short Duration Small Sided Football and to a Lesser Extent Whole Body Vibration Exercise Induce Acute Changes in Markers of Bone Turnover

    Science.gov (United States)

    Bowtell, J. L.; Jackman, S. R.; Scott, S.; Connolly, L. J.; Ermidis, G.; Julian, R.; Yousefian, F.; Helge, E. W.; Jørgensen, N. R.; Fulford, J.; Knapp, K. M.

    2016-01-01

    We aimed to study whether short-duration vibration exercise or football sessions of two different durations acutely changed plasma markers of bone turnover and muscle strain. Inactive premenopausal women (n = 56) were randomized to complete a single bout of short (FG15) or long duration (FG60) small sided football or low magnitude whole body vibration training (VIB). Procollagen type 1 amino-terminal propeptide (P1NP) was increased during exercise for FG15 (51.6 ± 23.0 to 56.5 ± 22.5 μg·L−1, mean ± SD, P 0.05). An increase in osteocalcin was observed 48 h after exercise (P < 0.05), which did not differ between exercise groups. C-terminal telopeptide of type 1 collagen was not affected by exercise. Blood lactate concentration increased during exercise for FG15 (0.6 ± 0.2 to 3.4 ± 1.2 mM) and FG60 (0.6 ± 0.2 to 3.3 ± 2.0 mM), but not for VIB (0.6 ± 0.2 to 0.8 ± 0.4 mM) (P < 0.05). Plasma creatine kinase increased by 55 ± 63% and 137 ± 119% 48 h after FG15 and FG60 (P < 0.05), but not after VIB (26 ± 54%, NS). In contrast to the minor elevation in osteocalcin in response to a single session of vibration exercise, both short and longer durations of small sided football acutely increased plasma P1NP, osteocalcin, and creatine kinase. This may contribute to favorable effects of chronic training on musculoskeletal health. PMID:28025642

  13. Short Duration Small Sided Football and to a Lesser Extent Whole Body Vibration Exercise Induce Acute Changes in Markers of Bone Turnover

    Directory of Open Access Journals (Sweden)

    J. L. Bowtell

    2016-01-01

    Full Text Available We aimed to study whether short-duration vibration exercise or football sessions of two different durations acutely changed plasma markers of bone turnover and muscle strain. Inactive premenopausal women (n=56 were randomized to complete a single bout of short (FG15 or long duration (FG60 small sided football or low magnitude whole body vibration training (VIB. Procollagen type 1 amino-terminal propeptide (P1NP was increased during exercise for FG15 (51.6±23.0 to 56.5±22.5 μg·L−1, mean ± SD, P0.05. An increase in osteocalcin was observed 48 h after exercise (P<0.05, which did not differ between exercise groups. C-terminal telopeptide of type 1 collagen was not affected by exercise. Blood lactate concentration increased during exercise for FG15 (0.6±0.2 to 3.4±1.2 mM and FG60 (0.6±0.2 to 3.3±2.0 mM, but not for VIB (0.6±0.2 to 0.8±0.4 mM (P<0.05. Plasma creatine kinase increased by 55±63% and 137±119% 48 h after FG15 and FG60 (P<0.05, but not after VIB (26±54%, NS. In contrast to the minor elevation in osteocalcin in response to a single session of vibration exercise, both short and longer durations of small sided football acutely increased plasma P1NP, osteocalcin, and creatine kinase. This may contribute to favorable effects of chronic training on musculoskeletal health.

  14. Drought history affects grassland plant and microbial carbon turnover during and after a subsequent drought event.

    Science.gov (United States)

    Fuchslueger, Lucia; Bahn, Michael; Hasibeder, Roland; Kienzl, Sandra; Fritz, Karina; Schmitt, Michael; Watzka, Margarete; Richter, Andreas

    2016-09-01

    Drought periods are projected to become more severe and more frequent in many European regions. While effects of single strong droughts on plant and microbial carbon (C) dynamics have been studied in some detail, impacts of recurrent drought events are still little understood.We tested whether the legacy of extreme experimental drought affects responses of plant and microbial C and nitrogen (N) turnover to further drought and rewetting. In a mountain grassland, we conducted a (13)C pulse-chase experiment during a naturally occurring drought and rewetting event in plots previously exposed to experimental droughts and in ambient controls (AC). After labelling, we traced (13)C below-ground allocation and incorporation into soil microbes using phospholipid fatty acid biomarkers.Drought history (DH) had no effects on the standing shoot and fine root plant biomass. However, plants with experimental DH displayed decreased shoot N concentrations and increased fine root N concentrations relative to those in AC. During the natural drought, plants with DH assimilated and allocated less (13)C below-ground; moreover, fine root respiration was reduced and not fuelled by fresh C compared to plants in AC.Regardless of DH, microbial biomass remained stable during natural drought and rewetting. Although microbial communities initially differed in their composition between soils with and without DH, they responded to the natural drought and rewetting in a similar way: gram-positive bacteria increased, while fungal and gram-negative bacteria remained stable. In soils with DH, a strongly reduced uptake of recent plant-derived (13)C in microbial biomarkers was observed during the natural drought, pointing to a smaller fraction of active microbes or to a microbial community that is less dependent on plant C. Synthesis. Drought history can induce changes in above- vs. below-ground plant N concentrations and affect the response of plant C turnover to further droughts and rewetting by

  15. Phospholipid barrier to fibrinolysis: role for the anionic polar head charge and the gel phase crystalline structure.

    Science.gov (United States)

    Váradi, Balázs; Kolev, Krasimir; Tenekedjiev, Kiril; Mészáros, Gyöngyi; Kovalszky, Ilona; Longstaff, Colin; Machovich, Raymund

    2004-09-17

    The massive presence of phospholipids is demonstrated in frozen sections of human arterial thrombi. Purified platelet phospholipids and synthetic phospholipids retard in vitro tissue-type plasminogen activator (tPA)-induced fibrinolysis through effects on plasminogen activation and plasmin function. The inhibition of plasminogen activation on the surface of fibrin correlates with the fraction of anionic phospholipid. The phospholipids decrease the amount of tPA penetrating into the clot by 75% and the depth of the reactive surface layer occupied by the activator by up to 30%, whereas for plasmin both of these parameters decrease by approximately 50%. The phospholipids are not only a diffusion barrier, they also bind the components of the fibrinolytic system. Isothermal titration calorimetry shows binding characterized with dissociation constants in the range 0.35-7.64 microm for plasmin and tPA (lower values with more negative phospholipids). The interactions are endothermic and thermodynamically driven by an increase in entropy, probably caused by the rearrangements in the ordered gel structure of the phospholipids (in line with the stronger inhibition at gel phase temperatures compared with liquid crystalline phase temperatures). These findings show a phospholipid barrier, which should be overcome during lysis of arterial thrombi.

  16. Phospholipid liposomes functionalized by protein

    Science.gov (United States)

    Glukhova, O. E.; Savostyanov, G. V.; Grishina, O. A.

    2015-03-01

    Finding new ways to deliver neurotrophic drugs to the brain in newborns is one of the contemporary problems of medicine and pharmaceutical industry. Modern researches in this field indicate the promising prospects of supramolecular transport systems for targeted drug delivery to the brain which can overcome the blood-brain barrier (BBB). Thus, the solution of this problem is actual not only for medicine, but also for society as a whole because it determines the health of future generations. Phospholipid liposomes due to combination of lipo- and hydrophilic properties are considered as the main future objects in medicine for drug delivery through the BBB as well as increasing their bioavailability and toxicity. Liposomes functionalized by various proteins were used as transport systems for ease of liposomes use. Designing of modification oligosaccharide of liposomes surface is promising in the last decade because it enables the delivery of liposomes to specific receptor of human cells by selecting ligand and it is widely used in pharmacology for the treatment of several diseases. The purpose of this work is creation of a coarse-grained model of bilayer of phospholipid liposomes, functionalized by specific to the structural elements of the BBB proteins, as well as prediction of the most favorable orientation and position of the molecules in the generated complex by methods of molecular docking for the formation of the structure. Investigation of activity of the ligand molecule to protein receptor of human cells by the methods of molecular dynamics was carried out.

  17. The use of natural and synthetic phospholipids as pharmaceutical excipients*

    Science.gov (United States)

    van Hoogevest, Peter; Wendel, Armin

    2014-01-01

    In pharmaceutical formulations, phospholipids obtained from plant or animal sources and synthetic phospholipids are used. Natural phospholipids are purified from, e.g., soybeans or egg yolk using non-toxic solvent extraction and chromatographic procedures with low consumption of energy and minimum possible waste. Because of the use of validated purification procedures and sourcing of raw materials with consistent quality, the resulting products differing in phosphatidylcholine content possess an excellent batch to batch reproducibility with respect to phospholipid and fatty acid composition. The natural phospholipids are described in pharmacopeias and relevant regulatory guidance documentation of the Food and Drug Administration (FDA) and European Medicines Agency (EMA). Synthetic phospholipids with specific polar head group, fatty acid composition can be manufactured using various synthesis routes. Synthetic phospholipids with the natural stereochemical configuration are preferably synthesized from glycerophosphocholine (GPC), which is obtained from natural phospholipids, using acylation and enzyme catalyzed reactions. Synthetic phospholipids play compared to natural phospholipid (including hydrogenated phospholipids), as derived from the number of drug products containing synthetic phospholipids, a minor role. Only in a few pharmaceutical products synthetic phospholipids are used. Natural phospholipids are used in oral, dermal, and parenteral products including liposomes. Natural phospholipids instead of synthetic phospholipids should be selected as phospholipid excipients for formulation development, whenever possible, because natural phospholipids are derived from renewable sources and produced with more ecologically friendly processes and are available in larger scale at relatively low costs compared to synthetic phospholipids. Practical applications: For selection of phospholipid excipients for pharmaceutical formulations, natural phospholipids are preferred

  18. Business Ethics & Employee Turnover: CAFE Matrix

    OpenAIRE

    Sapovadia, Vrajlal; Patel, Sweta

    2013-01-01

    Abstract: Business ethics is in discussion for its importance universally, so is the employee turnover in business. Unethical practices are unwanted, so is the high employee turnover. Unethical practices and high employee turnover in business is ubiquitous. No consensus exists on defining ethics. Employee turnover is well defined, but there is no consensus on when employee turnover is disadvantageous for the company. The Golden Rule or ethic of reciprocity, a maxim states that either ...

  19. The low levels of eicosapentaenoic acid in rat brain phospholipids are maintained via multiple redundant mechanisms.

    Science.gov (United States)

    Chen, Chuck T; Domenichiello, Anthony F; Trépanier, Marc-Olivier; Liu, Zhen; Masoodi, Mojgan; Bazinet, Richard P

    2013-09-01

    Brain eicosapentaenoic acid (EPA) levels are 250- to 300-fold lower than docosahexaenoic acid (DHA), at least partly, because EPA is rapidly β-oxidized and lost from brain phospholipids. Therefore, we examined if β-oxidation was necessary for maintaining low EPA levels by inhibiting β-oxidation with methyl palmoxirate (MEP). Furthermore, because other metabolic differences between DHA and EPA may also contribute to their vastly different levels, this study aimed to quantify the incorporation and turnover of DHA and EPA into brain phospholipids. Fifteen-week-old rats were subjected to vehicle or MEP prior to a 5 min intravenous infusion of (14)C-palmitate, (14)C-DHA, or (14)C-EPA. MEP reduced the radioactivity of brain aqueous fractions for (14)C-palmitate-, (14)C-EPA-, and (14)C-DHA-infused rats by 74, 54, and 23%, respectively; while it increased the net rate of incorporation of plasma unesterified palmitate into choline glycerophospholipids and phosphatidylinositol and EPA into ethanolamine glycerophospholipids and phosphatidylserine. MEP also increased the synthesis of n-3 docosapentaenoic acid (n-3 DPA) from EPA. Moreover, the recycling of EPA into brain phospholipids was 154-fold lower than DHA. Therefore, the low levels of EPA in the brain are maintained by multiple redundant pathways including β-oxidation, decreased incorporation from plasma unesterified FA pool, elongation/desaturation to n-3 DPA, and lower recycling within brain phospholipids.

  20. Microbial carbon turnover in the plant-rhizosphere-soil continuum

    Science.gov (United States)

    Malik, Ashish; Dannert, Helena; Griffiths, Robert; Thomson, Bruce; Gleixner, Gerd

    2014-05-01

    Soil microbial biomass contributes significantly to maintenance of soil organic matter (SOM). It is well known that biochemical fractions of soil microorganisms have varying turnover and therefore contribute differentially to soil C storage. Here we compare the turnover rates of different microbial biochemical fractions using a pulse chase 13CO2 plant labelling experiment. The isotope signal was temporally traced into rhizosphere soil microorganisms using the following biomarkers: DNA, RNA, fatty acids and chloroform fumigation extraction derived microbial biomass size classes. C flow into soil microbial functional groups was assessed through phospholipid and neutral lipid fatty acid (PLFA/NLFA) analyses. Highest 13C enrichment was seen in the low molecular weight (LMW) size class of microbial biomass (Δδ13C =151) and in nucleic acids (DNA: 38o RNA: 66) immediately after the pulse followed by a sharp drop. The amount of 13C in the high molecular weight (HMW) microbial biomass (17-81) and total fatty acids (32-54) was lower initially and stayed relatively steady over the 4 weeks experimental period. We found significant differences in turnover rates of different microbial biochemical and size fractions. We infer that LMW cytosolic soluble compounds are rapidly metabolized and linked to respiratory C fluxes, whereas mid-sized products of microbial degradation and HMW polymeric compounds have lower renewal rate in that order. The turnover of cell wall fatty acids was also very slow. DNA and RNA showed faster turnover rate; and as expected RNA renewal was the fastest due to its rapid production by active microorganisms independent of cell replication. 13C incorporation into different functional groups confirmed that mutualistic arbuscular mycorrhizal fungi rely on root C and are important in the initial plant C flux. We substantiated through measurements of isotope incorporation into bacterial RNA that rhizosphere bacteria are also important in the initial C conduit

  1. Effect of lead on lipid peroxidation, phospholipids composition, and methylation in erythrocyte of human.

    Science.gov (United States)

    Shafiq-ur-Rehman

    2013-09-01

    Lead (Pb) is one of the most abundant heavy metals on earth considered as number one environmental persistent toxin and health hazard affecting millions of people in all age groups. After entering bloodstream, 99% of Pb is accumulated in erythrocytes and causes poisoning. Toxic Pb effects on erythrocytes membrane's composition of phosphatidyl serine (PS), phosphatidyl ethanolamine (PE), phosphatidyl choline (PC), and sphingomyelin (SM), and phospholipids transmethylation were determined. Lipid peroxidation in Pb-exposed erythrocytes was evaluated as malondialdehyde (MDA) formation in presence of Fe and vitamin E to understand severity of Pb toxicity and its mitigation. Pb (0.5-5.0 μM) degraded PS (12 to 31%, P phospholipids in membranes (34, 41, and 50%, respectively, with 0.5, 2.5, and 5.0 μM). Pb-induced dose-related MDA production (P phospholipids, inhibition of transmethylation, and exasperated phospholipid peroxidative damage are the active phenomena of Pb toxicity in erythrocytes.

  2. Light and phospholipid driven structural transitions in nematic microdroplets

    Energy Technology Data Exchange (ETDEWEB)

    Dubtsov, A. V., E-mail: alexanderdubtsov@gmail.com; Pasechnik, S. V.; Shmeliova, D. V. [Moscow State University of Instrument Engineering and Computer Science, Stromynka 20, Moscow 107996 (Russian Federation); Kralj, Samo [Condensed Matter Physics Department, Jožef Stefan Institute, Jamova 39, 1000 Ljubljana (Slovenia); FNM, University of Maribor, Koroska 160, 2000 Maribor (Slovenia)

    2014-10-13

    We studied the UV-irradiation and phospholipid driven bipolar-radial structural transitions within azoxybenzene nematic liquid crystal (LC) droplets dispersed in water. It was found that the UV-irradiation induced trans-cis isomerisation of LC molecules could enable structural transitions into radial-type configurations at a critical UV-irradiation time t{sub c}. In particular, we show that under appropriate conditions, a value of t{sub c} could sensitively fingerprint the concentration of phospholipid molecules present in LC-water dispersions. This demonstrated proof-of-principle mechanism could be exploited for development of sensitive detectors for specific nanoparticles (NPs), where value of t{sub c} reveals concentration of NPs.

  3. Molecular Dynamic Analysis of Hyaluronic Acid and Phospholipid Interaction in Tribological Surgical Adjuvant Design for Osteoarthritis.

    Science.gov (United States)

    Siódmiak, Jacek; Bełdowski, Piotr; Augé, Wayne K; Ledziński, Damian; Śmigiel, Sandra; Gadomski, Adam

    2017-09-04

    Tribological surgical adjuvants constitute a therapeutic discipline made possible by surgical advances in the treatment of damaged articular cartilage beyond palliative care. The purpose of this study is to analyze interactions between hyaluronic acid and phospholipid molecules, and the formation of geometric forms, that play a role in the facilitated lubrication of synovial joint organ systems. The analysis includes an evaluation of the pathologic state to detail conditions that may be encountered by adjuvants during surgical convalescence. The synovial fluid changes in pH, hyaluronic acid polydispersity, and phospholipid concentration associated with osteoarthritis are presented as features that influence the lubricating properties of adjuvant candidates. Molecular dynamic simulation studies are presented, and the Rouse model is deployed, to rationalize low molecular weight hyaluronic acid behavior in an osteoarthritic environment of increased pH and phospholipid concentration. The results indicate that the hyaluronic acid radius of gyration time evolution is both pH- and phospholipid concentration-dependent. Specifically, dipalmitoylphosphatidylcholine induces hydrophobic interactions in the system, causing low molecular weight hyaluronic acid to shrink and at high concentration be absorbed into phospholipid vesicles. Low molecular weight hyaluronic acid appears to be insufficient for use as a tribological surgical adjuvant because an increased pH and phospholipid concentration induces decreased crosslinking that prevents the formation of supramolecular lubricating forms. Dipalmitoylphosphatidylcholine remains an adjuvant candidate for certain clinical situations. The need to reconcile osteoarthritic phenotypes is a prerequisite that should serve as a framework for future adjuvant design and subsequent tribological testing.

  4. Phospholipid Vesicles in Materials Science

    Energy Technology Data Exchange (ETDEWEB)

    Granick, Steve [Univ. of Illinois, Champaign, IL (United States)

    2016-05-11

    The objective of this research was to develop the science basis needed to deploy phospholipid vesicles as functional materials in energy contexts. Specifically, we sought to: (1) Develop an integrated molecular-level understanding of what determines their dynamical shape, spatial organization, and responsiveness to complex, time-varying environments; and (2) Develop understanding of their active transportation in crowded environments, which our preliminary measurements in cells suggest may hold design principles for targeting improved energy efficiency in new materials systems. The methods to do this largely involved fluorescence imaging and other spectroscopy involving single particles, vesicles, particles, DNA, and endosomes. An unexpected importance outcome was a new method to image light-emitting diodes during actual operation using super-resolution spectroscopy.

  5. Connexin channels and phospholipids: association and modulation

    Directory of Open Access Journals (Sweden)

    Harris Andrew L

    2009-08-01

    Full Text Available Abstract Background For membrane proteins, lipids provide a structural framework and means to modulate function. Paired connexin hemichannels form the intercellular channels that compose gap junction plaques while unpaired hemichannels have regulated functions in non-junctional plasma membrane. The importance of interactions between connexin channels and phospholipids is poorly understood. Results Endogenous phospholipids most tightly associated with purified connexin26 or connexin32 hemichannels or with junctional plaques in cell membranes, those likely to have structural and/or modulatory effects, were identified by tandem electrospray ionization-mass spectrometry using class-specific interpretative methods. Phospholipids were characterized by headgroup class, charge, glycerol-alkyl chain linkage and by acyl chain length and saturation. The results indicate that specific endogenous phospholipids are uniquely associated with either connexin26 or connexin32 channels, and some phospholipids are associated with both. Functional effects of the major phospholipid classes on connexin channel activity were assessed by molecular permeability of hemichannels reconstituted into liposomes. Changes to phospholipid composition(s of the liposome membrane altered the activity of connexin channels in a manner reflecting changes to the surface charge/potential of the membrane and, secondarily, to cholesterol content. Together, the data show that connexin26 and connexin32 channels have a preference for tight association with unique anionic phospholipids, and that these, independent of headgroup, have a positive effect on the activity of both connexin26 and connexin32 channels. Additionally, the data suggest that the likely in vivo phospholipid modulators of connexin channel structure-function that are connexin isoform-specific are found in the cytoplasmic leaflet. A modulatory role for phospholipids that promote negative curvature is also inferred. Conclusion

  6. Chk1 regulates the S phase checkpoint by coupling the physiological turnover and ionizing radiation-induced accelerated proteolysis of Cdc25A

    DEFF Research Database (Denmark)

    Sørensen, Claus Storgaard; Syljuåsen, Randi G; Falck, Jacob

    2003-01-01

    Chk1 kinase coordinates cell cycle progression and preserves genome integrity. Here, we show that chemical or genetic ablation of human Chk1 triggered supraphysiological accumulation of the S phase-promoting Cdc25A phosphatase, prevented ionizing radiation (IR)-induced degradation of Cdc25A...

  7. CEO Turnover and Market Reaction in Indonesia

    Directory of Open Access Journals (Sweden)

    Doddy Setiawan

    2013-07-01

    Full Text Available This research examines Chief Executive Officer (CEO turnover and market reaction in Indonesia. The sample of this research consists of 213 CEO turnover announcements for Indonesia Stock Exchange during 2000–2010 period. T-tests were used to investigate the effect of CEO turnover announcement on abnormal stock return during the event windows periods. The results of this research show that there is positive reaction on the CEO turnover announcements. This research considers both routine and non routine CEO turnover processes. This research finds that both turnover processes have information content to investor. This research also finds positive reaction on the announcements of outsider incoming CEO, while investors do not react on the announcement of insider incoming CEO. Thus, this research provides evidence that CEO turnover announcement have information content.   Keywords: CEO turnover, stock price, turnover process, the origin of incoming CEO

  8. The role of zinc deficiency-induced changes in the phospholipid-protein balance of blood serum in animal depression model by Raman, FTIR and UV-vis spectroscopy.

    Science.gov (United States)

    Depciuch, J; Sowa-Kućma, M; Nowak, G; Szewczyk, B; Doboszewska, U; Parlinska-Wojtan, M

    2017-05-01

    Depression is a serious mental illness. To study the mechanisms of diseases and search for new, more effective therapies, animal models are used. Unfortunately, none of the available models does reflect all symptoms of depression. Zinc deficiency is proposed as a new animal model of depression. However, it has not been yet validated in a detailed manner. Recently, spectroscopic techniques are increasingly being used both in clinical and preclinical studies. Here we examined the effect of zinc deficiency and amitryptyline treatment on the phospholipid - protein balance in the blood serum of rats using Raman, Fourier Transform Infra Red (FTIR) and UV-vis technique. Male Sprague Dawley rats were fed with a zinc ample diet (ZnA, 50mg Zn/kg) or a zinc deficient diet (ZnD, 3mg Zn/kg) for 4 weeks. Then amitriptyline administration (AMI, 10mg/kg, i.p.) was started. After injecting the drug for 2-weeks, blood samples were collected and analyzed. It was found that zinc deficiency decreases both the level of phospholipids and proteins and also causes structural changes in their structures. In the ZnD group amitriptyline treatment influenced the protein level and structure. UV-vis spectroscopy combined with the second derivative calculated from the FTIR spectra provided information that the proteins in blood serum of rat fed with a low Zn diet regain their intact structure after amitriptyline medication. Simultaneously, the antidepressant therapy did not have any effect on the level of phospholipids in this group of rats. Additionally, our results show, that amitriptyline administration can change the structure of phospholipids in rats subjected to zinc ample diet. This altered structure of phospholipids was identified as shortening of carbon chains. Our findings indicate that the decreased level of zinc may be the cause of depressive disorders, as it leads to changes in the phospholipid-protein balance necessary for the proper functioning of the body. This study also shows

  9. Job turnover and labor turnover : a taxonomy of employment dynamics

    NARCIS (Netherlands)

    Hassink, Wolter H.J.; Hamermesh, Daniel S.

    1994-01-01

    We present an organized set of stylized facts on the relations among flows of workers,changes in employment and changes in the numer of jobs at the firm level. Job turnover isusually measured by comparing stocks of employment in each firm at two points in time andadding up the absolute employment ch

  10. Mitochondrial phospholipids: role in mitochondrial function.

    Science.gov (United States)

    Mejia, Edgard M; Hatch, Grant M

    2016-04-01

    Mitochondria are essential components of eukaryotic cells and are involved in a diverse set of cellular processes that include ATP production, cellular signalling, apoptosis and cell growth. These organelles are thought to have originated from a symbiotic relationship between prokaryotic cells in an effort to provide a bioenergetic jump and thus, the greater complexity observed in eukaryotes (Lane and Martin 2010). Mitochondrial processes are required not only for the maintenance of cellular homeostasis, but also allow cell to cell and tissue to tissue communication (Nunnari and Suomalainen 2012). Mitochondrial phospholipids are important components of this system. Phospholipids make up the characteristic outer and inner membranes that give mitochondria their shape. In addition, these membranes house sterols, sphingolipids and a wide variety of proteins. It is the phospholipids that also give rise to other characteristic mitochondrial structures such as cristae (formed from the invaginations of the inner mitochondrial membrane), the matrix (area within cristae) and the intermembrane space (IMS) which separates the outer mitochondrial membrane (OMM) and inner mitochondrial membrane (IMM). Phospholipids are the building blocks that make up these structures. However, the phospholipid composition of the OMM and IMM is unique in each membrane. Mitochondria are able to synthesize some of the phospholipids it requires, but the majority of cellular lipid biosynthesis takes place in the endoplasmic reticulum (ER) in conjunction with the Golgi apparatus (Fagone and Jackowski 2009). In this review, we will focus on the role that mitochondrial phospholipids play in specific cellular functions and discuss their biosynthesis, metabolism and transport as well as the differences between the OMM and IMM phospholipid composition. Finally, we will focus on the human diseases that result from disturbances to mitochondrial phospholipids and the current research being performed to help

  11. Nonphotochemical quenching of excitation energy in photosystem II. A picosecond time-resolved study of the low yield of chlorophyll a fluorescence induced by single-turnover flash in isolated spinach thylakoids.

    Science.gov (United States)

    Vasil'ev, S; Bruce, D

    1998-08-04

    Chlorophyll a fluorescence emission is widely used as a noninvasive measure of a number of parameters related to photosynthetic efficiency in oxygenic photosynthetic organisms. The most important component for the estimation of photochemistry is the relative increase in fluorescence yield between dark-adapted samples which have a maximal capacity for photochemistry and a minimal fluorescence yield (F0) and light-saturated samples where photochemistry is saturated and fluorescence yield is maximal (Fm). However, when photosynthesis is saturated with a short (less than 50 micro(s)) flash of light, which induces only one photochemical turnover of photosystem II, the maximal fluorescence yield is significantly lower (Fsat) than when saturation is achieved with a millisecond duration multiturnover flash (Fm). To investigate the origins of the difference in fluorescence yield between these two conditions, our time-resolved fluorescence apparatus was modified to allow collection of picosecond time-resolved decay kinetics over a short time window immediately following a saturating single-turnover flash (Fsat) as well as after a multiturnover saturating pulse (Fm). Our data were analyzed with a global kinetic model based on an exciton radical pair equilibrium model for photosystem II. The difference between Fm and Fsat was modeled well by changing only the rate constant for quenching of excitation energy in the antenna of photosystem II. An antenna-based origin for the quenching was verified experimentally by the observation that addition of the antenna quencher 5-hydroxy-1,4-naphthoquinone to thylakoids under Fm conditions resulted in decay kinetics and modeled kinetic parameters very similar to those observed under Fsat conditions in the absence of added quinone. Our data strongly support the origin of low fluorescence yield at Fsat to be an antenna-based nonphotochemical quenching of excitation energy in photosystem II which has not usually been considered explicitly in

  12. Lipid peroxidation generates biologically active phospholipids including oxidatively N-modified phospholipids.

    Science.gov (United States)

    Davies, Sean S; Guo, Lilu

    2014-07-01

    Peroxidation of membranes and lipoproteins converts "inert" phospholipids into a plethora of oxidatively modified phospholipids (oxPL) that can act as signaling molecules. In this review, we will discuss four major classes of oxPL: mildly oxygenated phospholipids, phospholipids with oxidatively truncated acyl chains, phospholipids with cyclized acyl chains, and phospholipids that have been oxidatively N-modified on their headgroups by reactive lipid species. For each class of oxPL we will review the chemical mechanisms of their formation, the evidence for their formation in biological samples, the biological activities and signaling pathways associated with them, and the catabolic pathways for their elimination. We will end by briefly highlighting some of the critical questions that remain about the role of oxPL in physiology and disease.

  13. Biochemical markers of bone turnover

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Deog Yoon [College of Medicine, Kyunghee Univ., Seoul (Korea, Republic of)

    1999-08-01

    Biochemical markers of bone turnover has received increasing attention over the past few years, because of the need for sensitivity and specific tool in the clinical investigation of osteoporosis. Bone markers should be unique to bone, reflect changes of bone less, and should be correlated with radiocalcium kinetics, histomorphometry, or changes in bone mass. The markers also should be useful in monitoring treatment efficacy. Although no bone marker has been established to meet all these criteria, currently osteocalcin and pyridinium crosslinks are the most efficient markers to assess the level of bone turnover in the menopausal and senile osteoporosis. Recently, N-terminal telopeptide (NTX), C-terminal telopeptide (CTX) and bone specific alkaline phosphatase are considered as new valid markers of bone turnover. Recent data suggest that CTX and free deoxypyridinoline could predict the subsequent risk of hip fracture of elderly women. Treatment of postmenopausal women with estrogen, calcitonin and bisphosphonates demonstrated rapid decrease of the levels of bone markers that correlated with the long-term increase of bone mass. Factors such as circadian rhythms, diet, age, sex, bone mass and renal function affect the results of biochemical markers and should be appropriately adjusted whenever possible. Each biochemical markers of bone turnover may have its own specific advantages and limitations. Recent advances in research will provide more sensitive and specific assays.

  14. Effect of pineapple peel extract on total phospholipids and lipid peroxidation in brain tissues of rats

    Institute of Scientific and Technical Information of China (English)

    Erukainure OL; Ajiboye JA; Adejobi RO; Okafor OY; Kosoko SB; Owolabi FO

    2011-01-01

    Objective:To investigate the ability of the methanolic extract of pineapple peel to attenuate alcohol-induced changes in total phospholipids and lipid peroxidation in brain tissues. Methods:Oxidative stress was induced by oral administration of ethanol (20%w/v) at a dosage of 5 mL/kg bw in rats. After 28 days of treatment, the rats were fasted overnight and sacrificed by cervical dislocation. Brain tissues were assayed for total phospholipid (TP) content and malondialdehyde (MDA). Results:Administration of alcohol significantly caused a reduction in TP content. Treatment with pineapple peel extract significantly increased the TP content. Significant high levels of MDA was observed in alcohol-fed rats, treatment with pineapple peel extract significantly reduced the MDA levels. Conclusions:Results obtained from this study indicates that pineapple peel extract protects against alcohol-induced changes in total phospholipids and lipid peroxidation in brain tissues.

  15. Penetration of surfactin into phospholipid monolayers: nanoscale interfacial organization.

    Science.gov (United States)

    Eeman, M; Berquand, A; Dufrêne, Y F; Paquot, M; Dufour, S; Deleu, M

    2006-12-19

    Atomic force microscopy (AFM) combined with surface pressure-area isotherms were used to probe the interfacial behavior of phospholipid monolayers following penetration of surfactin, a cyclic lipopeptide produced by Bacillus subtilis strains. Prior to penetration experiments, interfacial behavior of different surfactin molecules (cyclic surfactins with three different aliphatic chain lengths--S13, S14, and S15--and a linear surfactin obtained by chemical cleavage of the cycle of the surfactin S15) has been investigated. A more hydrophobic aliphatic chain induces greater surface-active properties of the lipopeptide. The opening of the peptide ring reduces the surface activity. The effect of phospholipid acyl chain length (dimyristoylphosphatidylcholine, dipalmitoylphosphatidylcholine- (DPPC), and distearoylphosphatidylcholine) and phospholipid polar head (DPPC, dipalmitoylphosphatidylethanolamine and dipalmitoylphosphatidylserine) on monolayer penetration properties of the surfactin S15 has been explored. Results showed that while the lipid monolayer thickness and the presence of electrostatic repulsions from the interfacial film do not significantly influence surfactin insertion, these parameters strongly modulate the ability of the surfactin to alter the nanoscale organization of the lipid films. We also probed the effect of surfactin structure (influence of the aliphatic chain length and of the cyclic structure of the peptide ring) on the behavior of DPPC monolayers. AFM images and isotherms showed that surfactin penetration is promoted by longer lipopeptide chain length and a cyclic polar head. This indicates that hydrophobic interactions are of main importance for the penetration power of surfactin molecules.

  16. Peroxidase activation of cytoglobin by anionic phospholipids: Mechanisms and consequences.

    Science.gov (United States)

    Tejero, Jesús; Kapralov, Alexandr A; Baumgartner, Matthew P; Sparacino-Watkins, Courtney E; Anthonymutu, Tamil S; Vlasova, Irina I; Camacho, Carlos J; Gladwin, Mark T; Bayir, Hülya; Kagan, Valerian E

    2016-05-01

    Cytoglobin (Cygb) is a hexa-coordinated hemoprotein with yet to be defined physiological functions. The iron coordination and spin state of the Cygb heme group are sensitive to oxidation of two cysteine residues (Cys38/Cys83) and/or the binding of free fatty acids. However, the roles of redox vs lipid regulators of Cygb's structural rearrangements in the context of the protein peroxidase competence are not known. Searching for physiologically relevant lipid regulators of Cygb, here we report that anionic phospholipids, particularly phosphatidylinositolphosphates, affect structural organization of the protein and modulate its iron state and peroxidase activity both conjointly and/or independently of cysteine oxidation. Thus, different anionic lipids can operate in cysteine-dependent and cysteine-independent ways as inducers of the peroxidase activity. We establish that Cygb's peroxidase activity can be utilized for the catalysis of peroxidation of anionic phospholipids (including phosphatidylinositolphosphates) yielding mono-oxygenated molecular species. Combined with the computational simulations we propose a bipartite lipid binding model that rationalizes the modes of interactions with phospholipids, the effects on structural re-arrangements and the peroxidase activity of the hemoprotein.

  17. Maternal Baicalin Treatment Increases Fetal Lung Surfactant Phospholipids in Rats

    Directory of Open Access Journals (Sweden)

    Chung-Ming Chen

    2011-01-01

    Full Text Available Baicalin is a flavonoid compound purified from the medicinal plant Scutellaria baicalensis Georgi and has been reported to stimulate surfactant protein (SP-A gene expression in human lung epithelial cell lines (H441. The aims of this study were to determine whether maternal baicalin treatment could increase lung surfactant production and induce lung maturation in fetal rats. This study was performed with timed pregnant Sprague-Dawley rats. One-day baicalin group mothers were injected intraperitoneally with baicalin (5 mg/kg/day on Day 18 of gestation. Two-day baicalin group mothers were injected intraperitoneally with baicalin (5 mg/kg/day on Days 17 and 18 of gestation. Control group mothers were injected with vehicle alone on Day 18 of gestation. On Day 19 of gestation, fetuses were delivered by cesarean section. Maternal treatment with 2-day baicalin significantly increased saturated phospholipid when compared with control group and total phospholipid in fetal lung tissue when compared with control and 1-day baicalin groups. Antenatal treatment with 2-day baicalin significantly increased maternal growth hormone when compared with control group. Fetal lung SP-A mRNA expression and maternal serum corticosterone levels were comparable among the three experimental groups. Maternal baicalin treatment increases pulmonary surfactant phospholipids of fetal rat lungs and the improvement was associated with increased maternal serum growth hormone. These results suggest that antenatal baicalin treatment might accelerate fetal rat lung maturation.

  18. Qualitative and quantitative changes in phospholipids and proteins investigated by spectroscopic techniques in animal depression model

    Science.gov (United States)

    Depciuch, J.; Sowa-Kucma, M.; Nowak, G.; Papp, M.; Gruca, P.; Misztak, P.; Parlinska-Wojtan, M.

    2017-04-01

    Depression becomes nowadays a high mortality civilization disease with one of the major causes being chronic stress. Raman, Fourier Transform Infra Red (FTIR) and Ultraviolet-Visible (UV-vis) spectroscopies were used to determine the changes in the quantity and structure of phospholipids and proteins in the blood serum of rats subjected to chronic mild stress, which is a common animal depression model. Moreover, the efficiency of the imipramine treatment was evaluated. It was found that chronic mild stress not only damages the structure of the phospholipids and proteins, but also decreases their level in the blood serum. A 5 weeks imipramine treatment did increase slightly the quantity of proteins, leaving the damaged phospholipids unchanged. Structural information from phospholipids and proteins was obtained by UV-vis spectroscopy combined with the second derivative of the FTIR spectra. Indeed, the structure of proteins in blood serum of stressed rats was normalized after imipramine therapy, while the impaired structure of phospholipids remained unaffected. These findings strongly suggest that the depression factor, which is chronic mild stress, may induce permanent (irreversible) damages into the phospholipid structure identified as shortened carbon chains. This study shows a possible new application of spectroscopic techniques in the diagnosis and therapy monitoring of depression.

  19. Cell signalling and phospholipid metabolism. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Boss, W.F.

    1990-12-31

    These studies explored whether phosphoinositide (PI) has a role in plants analogous to its role in animal cells. Although no parallel activity of PI in signal transduction was found in plant cells, activity of inositol phospholipid kinase was found to be modulated by light and by cell wall degrading enzymes. These studies indicate a major role for inositol phospholipids in plant growth and development as membrane effectors but not as a source of second messengers.

  20. Phospholipids as Biomarkers for Excessive Alcohol Use

    Science.gov (United States)

    2013-10-01

    S.T., Bauman, K.E., & Foshee, V. A. (2005). Neighborhood Influences on Adolescent Cigarette and Alcohol Use: Mediating Effects through Parent and...AWARD NUMBER: W81XWH-12-1-0497 TITLE: Phospholipids as Biomarkers for Excessive Alcohol Use...NUMBER Phospholipids as Biomarkers for Excessive Alcohol Use 5b. GRANT NUMBER W81XWH-12-1-0497 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S

  1. Enzymatic modification of phospholipids forfunctional applications and human nutrition

    DEFF Research Database (Denmark)

    Guo, Zheng; Vikbjerg, Anders / Falk; Xu, Xuebing

    2005-01-01

    Rapid progress in biochemistry of phospholipids and evolution of modern bioengineering has brought forth a number of novel concepts and technical advancements in the modification of phospholipids for industrial applications and human nutrition. Highlights cover preparation of novel phospholipid...... analogs based on the latest understanding of pivotal role of phospholipids in manifold biological processes, exploration of remarkable application potentials of phospholipids in meliorating human health, as well as development of new chemical and biotechnological approaches applied to the modification...

  2. Gravimetric determination of phospholipid concentration.

    Science.gov (United States)

    Tejera-Garcia, Roberto; Connell, Lisa; Shaw, Walter A; Kinnunen, Paavo K J

    2012-09-01

    Accurate determination of lipid concentrations is an obligatory routine in a research laboratory engaged in studies using this class of biomaterials. For phospholipids, this is frequently accomplished using the phosphate assay (Bartlett, G.R. Phosphorus Assay in Column Chromatography. J. Biol. Chem. 234, 466-468, 1959). Given the purity of the currently commercially available synthetic and isolated natural lipids, we have observed that determination of the dry weight of lipid stock solutions provides the fastest, most accurate, and generic method to assay their concentrations. The protocol described here takes advantage of the high resolution and accuracy obtained by modern weighing technology. We assayed by this technique the concentrations of a number of phosphatidylcholine samples, with different degrees of acyl chain saturation and length, and in different organic solvents. The results were compared with those from Bartlett assay, (31)P NMR, and Langmuir compression isotherms. The data obtained show that the gravimetric assay yields lipid concentrations with a resolution similar or better than obtained by the other techniques.

  3. How Teacher Turnover Harms Student Achievement

    Science.gov (United States)

    Ronfeldt, Matthew; Loeb, Susanna; Wyckoff, James

    2013-01-01

    Researchers and policymakers often assume that teacher turnover harms student achievement, though recent studies suggest this may not be the case. Using a unique identification strategy that employs school-by-grade level turnover and two classes of fixed-effects models, this study estimates the effects of teacher turnover on over 850,000 New York…

  4. A literature review of nursing turnover costs.

    Science.gov (United States)

    Li, Yin; Jones, Cheryl B

    2013-04-01

    To report the findings of a literature review of studies examining nursing staff turnover costs published between 1990 and 2010. Nurse turnover is a global concern that is both costly for health-care organizations and, in the context of the work environment, affects quality and safety. We reviewed past literature and describe the conceptualization of nurse turnover, evaluate the methodologies and calculation of costs, identify the reported range of turnover costs and provide suggestions for future study. We report inconsistencies in past studies in terms of the conceptualization and measurement of nurse turnover and turnover rates, the methodologies for gathering data and the data sources used, the approaches for calculating turnover costs and the resulting nursing staff turnover costs estimated. Past studies reached different conclusions about nurse turnover. We still need to explore the actual costs and benefits of nurse turnover and retention. This study should be helpful for nurse executives as they build a business case to address nurse turnover in their organizations, and for policy-makers as they develop policies about turnover. © 2012 Blackwell Publishing Ltd.

  5. Measuring Staff Turnover in Nursing Homes

    Science.gov (United States)

    Castle, Nicholas G.

    2006-01-01

    Purpose: In this study the levels of staff turnover reported in the nursing home literature (1990-2003) are reviewed, as well as the definitions of turnover used in these prior studies. With the use of primary data collected from 354 facilities, the study addresses the various degrees of bias that result, depending on how staff turnover is defined…

  6. Using Turnover as a Recruitment Strategy

    Science.gov (United States)

    Duncan, Sandra

    2009-01-01

    Teacher turnover is notoriously high in the field of early childhood education with an estimated 33% of staff exiting the workplace each year. Turnover is costly. Not only do high levels of turnover negatively impact children's growth and development, it also erodes the program's economic stability and wherewithal to provide effective operations…

  7. Ginkgolide B Reduces the Degradation of Membrane Phospholipids to Prevent Ischemia/Reperfusion Myocardial Injury in Rats.

    Science.gov (United States)

    Pei, Hong-Xia; Hua, Rong; Guan, Cha-Xiang; Fang, Xiang

    2015-01-01

    Platelet-activating factor (PAF), a bioactive phospholipid, plays an important role in the integrity of the cellular membrane structure, and is involved in the pathogenesis of myocardial ischemia/reperfusion (IR) injuries. In this study, we tested the hypothesis that blockage of PAF receptor by BN 52021 (Ginkgolide B) can prevent IR-induced degradation of the myocardial membrane phospholipid, and deterioration of the cardiac function. Rat hearts in situ were subjected to 5 min ischemia and followed by 10 min reperfusion. Cardiac performances during periods of ischemia and reperfusion were monitored, and the amount of membrane phospholipids was analyzed. Myocardial total phospholipids, phosphatidylcholine, and phosphatidylethanolamine were decreased significantly in ischemia-reperfusion rat hearts compared with those of sham-operated rat hearts. Degradation of the membrane phospholipid was accompanied by the deterioration of cardiac functions and increase in serum lactate dehydrogenase (LDH) activity. BN 52021 (15 mg/kg), given by intravenous infusion 10 min prior to the left anterior descending coronary artery occlusion, reduced IR-related degradation of the myocardial phospholipids, the activity of serum LDH, and was concomitant with improvement of cardiac function. Furthermore, we demonstrated that the production of PAF was increased and BN 52021 decreased cellular damage in cultured anoxic cardiomyocytes. These results indicated that PAF antagonist BN 52021 has a protective effect against IR-induced myocardial dysfunction and degradation of the membrane phospholipids.

  8. Membrane phospholipid augments cytochrome P4501a enzymatic activity by modulating structural conformation during detoxification of xenobiotics.

    Directory of Open Access Journals (Sweden)

    Manik C Ghosh

    Full Text Available Cytochrome P450 is a superfamily of membrane-bound hemoprotein that gets involved with the degradation of xenobiotics and internal metabolites. Accumulated body of evidence indicates that phospholipids play a crucial role in determining the enzymatic activity of cytochrome P450 in the microenvironment by modulating its structure during detoxification; however, the structure-function relationship of cytochrome P4501A, a family of enzymes responsible for degrading lipophilic aromatic hydrocarbons, is still not well defined. Inducibility of cytochrome P4501A in cultured catfish hepatocytes in response to carbofuran, a widely used pesticide around the world, was studied earlier in our laboratory. In this present investigation, we observed that treating catfish with carbofuran augmented total phospholipid in the liver. We examined the role of phospholipid on the of cytochrome P4501A-marker enzyme which is known as ethoxyresorufin-O-deethylase (EROD in the context of structure and function. We purified the carbofuran-induced cytochrome P4501A protein from catfish liver. Subsequently, we examined the enzymatic activity of purified P4501A protein in the presence of phospholipid, and studied how the structure of purified protein was influenced in the phospholipid environment. Membrane phospholipid appeared to accelerate the enzymatic activity of EROD by changing its structural conformation and thus controlling the detoxification of xenobiotics. Our study revealed the missing link of how the cytochrome P450 restores its enzymatic activity by changing its structural conformation in the phospholipid microenvironment.

  9. Turnover: strategies for staff retention.

    Science.gov (United States)

    SnowAntle, S

    1990-01-01

    This discussion has focused on a number of areas where organizations may find opportunities for more effectively managing employee retention. Given the multitude of causes and consequences, there is no one quick fix. Effective management of employee retention requires assessment of the entire human resources process, that is, recruitment, selection, job design, compensation, supervision, work conditions, etc. Regular and systematic diagnosis of turnover and implementation of multiple strategies and evaluation are needed (Mobley, 1982).

  10. Health effects of dietary phospholipids

    Directory of Open Access Journals (Sweden)

    Küllenberg Daniela

    2012-01-01

    Full Text Available Abstract Beneficial effects of dietary phospholipids (PLs have been mentioned since the early 1900's in relation to different illnesses and symptoms, e.g. coronary heart disease, inflammation or cancer. This article gives a summary of the most common therapeutic uses of dietary PLs to provide an overview of their approved and proposed benefits; and to identify further investigational needs. From the majority of the studies it became evident that dietary PLs have a positive impact in several diseases, apparently without severe side effects. Furthermore, they were shown to reduce side effects of some drugs. Both effects can partially be explained by the fact that PL are highly effective in delivering their fatty acid (FA residues for incorporation into the membranes of cells involved in different diseases, e.g. immune or cancer cells. The altered membrane composition is assumed to have effects on the activity of membrane proteins (e.g. receptors by affecting the microstructure of membranes and, therefore, the characteristics of the cellular membrane, e.g. of lipid rafts, or by influencing the biosynthesis of FA derived lipid second messengers. However, since the FAs originally bound to the applied PLs are increased in the cellular membrane after their consumption or supplementation, the FA composition of the PL and thus the type of PL is crucial for its effect. Here, we have reviewed the effects of PL from soy, egg yolk, milk and marine sources. Most studies have been performed in vitro or in animals and only limited evidence is available for the benefit of PL supplementation in humans. More research is needed to understand the impact of PL supplementation and confirm its health benefits.

  11. Nonenzymatic Reactions above Phospholipid Surfaces of Biological Membranes: Reactivity of Phospholipids and Their Oxidation Derivatives.

    Science.gov (United States)

    Solís-Calero, Christian; Ortega-Castro, Joaquín; Frau, Juan; Muñoz, Francisco

    2015-01-01

    Phospholipids play multiple and essential roles in cells, as components of biological membranes. Although phospholipid bilayers provide the supporting matrix and surface for many enzymatic reactions, their inherent reactivity and possible catalytic role have not been highlighted. As other biomolecules, phospholipids are frequent targets of nonenzymatic modifications by reactive substances including oxidants and glycating agents which conduct to the formation of advanced lipoxidation end products (ALEs) and advanced glycation end products (AGEs). There are some theoretical studies about the mechanisms of reactions related to these processes on phosphatidylethanolamine surfaces, which hypothesize that cell membrane phospholipids surface environment could enhance some reactions through a catalyst effect. On the other hand, the phospholipid bilayers are susceptible to oxidative damage by oxidant agents as reactive oxygen species (ROS). Molecular dynamics simulations performed on phospholipid bilayers models, which include modified phospholipids by these reactions and subsequent reactions that conduct to formation of ALEs and AGEs, have revealed changes in the molecular interactions and biophysical properties of these bilayers as consequence of these reactions. Then, more studies are desirable which could correlate the biophysics of modified phospholipids with metabolism in processes such as aging and diseases such as diabetes, atherosclerosis, and Alzheimer's disease.

  12. Detection and biological activities of carboxyethylpyrrole ethanolamine phospholipids (CEP-EPs).

    Science.gov (United States)

    Wang, Hua; Guo, Junhong; West, Xiaoxia Z; Bid, Hemant K; Lu, Liang; Hong, Li; Jang, Geeng-Fu; Zhang, Lei; Crabb, John W; Linetsky, Mikhail; Salomon, Robert G

    2014-12-15

    Oxidation of docosahexaenoate phospholipids produces 4-hydroxy-7-oxo-hept-5-eonyl phospholipids (HOHA-PLs) that react with protein lysyl ε-amino residues to generate 2-ω-carboxyethylpyrrole (CEP) derivatives, endogenous factors that induce angiogenesis in the retina and tumors. It seemed likely, but remained unproven, that HOHA-PLs react with ethanolamine phospholipids (EPs) in vivo to generate CEP-EPs. We now show that CEP-EPs are present in human blood at 4.6-fold higher levels in age-related macular degeneration plasma than in normal plasma. We also show that CEP-EPs are pro-angiogenic, inducing tube formation by human umbilical vein endothelial cells by activating Toll-like receptor 2. CEP-EP levels may be a useful biomarker for clinical assessment of AMD risk and CEP-associated tumor progression and a tool for monitoring the efficacy of therapeutic interventions.

  13. Quantification of phospholipids classes in human milk.

    Science.gov (United States)

    Giuffrida, Francesca; Cruz-Hernandez, Cristina; Flück, Brigitte; Tavazzi, Isabelle; Thakkar, Sagar K; Destaillats, Frédéric; Braun, Marcel

    2013-10-01

    Phospholipids are integral constituents of the milk fat globule membranes and they play a central role in infants' immune and inflammatory responses. A methodology employing liquid chromatography coupled with evaporative light scattering detector has been optimized and validated to quantify the major phospholipids classes in human milk. Phospholipids were extracted using chloroform and methanol and separated on C18 column. Repeatability, intermediate reproducibility, and recovery values were calculated and a large sample set of human milk analyzed. In human milk, phospholipid classes were quantified at concentrations of 0.6 mg/100 g for phosphatidylinositol; 4.2 mg/100 g for phosphatidylethanolamine, 0.4 mg/100 g for phosphatidylserine, 2.8 mg/100 g for phosphatidylcholine, and 4.6 mg/100 g for sphingomyelin. Their relative standard deviation of repeatability and intermediate reproducibility values ranging between 0.8 and 13.4 % and between 2.4 and 25.7 %, respectively. The recovery values ranged between 67 and 112 %. Finally, the validated method was used to quantify phospholipid classes in human milk collected from 50 volunteers 4 weeks postpartum providing absolute content of these lipids in a relatively large cohort. The average content of total phospholipids was 23.8 mg/100 g that corresponds to an estimated mean intake of 140 mg phospholipids/day in a 4-week old infant when exclusively breast-fed.

  14. Supervisory turnover in outpatient substance abuse treatment.

    Science.gov (United States)

    Knight, Danica K; Broome, Kirk M; Edwards, Jennifer R; Flynn, Patrick M

    2011-01-01

    Staff turnover is a significant issue within substance abuse treatment, with implications for service delivery and organizational health. This study examined factors associated with turnover among supervisors in outpatient substance abuse treatment. Turnover was conceptualized as being an individual response to organizational-level influences, and predictors represent aggregate program measures. Participants included 532 staff (including 467 counselors and 65 clinical/program directors) from 90 programs in four regions of the USA. Using logistic regression, analyses of structural factors indicated that programs affiliated with a parent organization and those providing more counseling hours to clients had higher turnover rates. When measures of job attitudes were included, only parent affiliation and collective appraisal of satisfaction were related to turnover. Subsequent analyses identified a trend toward increased supervisory turnover when satisfaction was low following the departure of a previous supervisor. These findings suggest that organizational-level factors can be influential in supervisory turnover.

  15. Kinetics of the activation of human prothrombin by human coagulation factor Xa. Initial rate studies in the presence of Ca2+ and phospholipid.

    Science.gov (United States)

    Kosow, D P; Orthner, C L

    1979-10-10

    Steady state kinetic studies have been performed to investigate the formation of thrombin from prothrombin by human coagulation Factor Xa in the presence of Ca2+ and phospholipid. The concentration of ligand which gives 50% of the maximum velocity (K0.5) is 2.3 mM for Ca2+, 7.4 microM for phospholipid, and 0.006 microM for prothrombin. Hill plots of the Ca2+ enhancement of the reaction give a Hill coefficient of 3.1, indicating positive cooperativity. The initial velocity patterns are consistent with an ordered addition of reactants with phospholipid as the second reactant to bind to the enzyme. Although our results do not differentiate between Ca2+ or the prothrombin substrate as the first reactant to bind to Factor Xa, it is established that Ca2+ can bind to Factor Xa in the absence of the other reactants. Thus, the most probable order of addition of reactants is Ca2+, phospholipid, and the prothrombin substrate. Plots of (v)-1 versus (prothrombin)-1 or (v)-1 versus [(Ca2+)3]-1 at several constant concentrations of phospholipid indicate that the major effect of phospholipid is to increase the turnover number of Factor Xa.

  16. Interaction of fluorescent phospholipids with cyclodextrins.

    Science.gov (United States)

    Denz, Manuela; Haralampiev, Ivan; Schiller, Sabine; Szente, Lajos; Herrmann, Andreas; Huster, Daniel; Müller, Peter

    2016-01-01

    Fluorescent analogs of phospholipids are often employed to investigate the structure and dynamics of lipids in membranes. Some of those studies have used cyclodextrins e.g., to modulate the lipid phase. However, the role of the fluorescence moiety of analogs for the interaction between cyclodextrins and fluorescent lipids has not been investigated so far in detail. Therefore, in the present study the interaction of various fluorescent phospholipid analogs with methylated α-, β- and γ- cyclodextrins was investigated. The analogs differed in their structure, in the length of the fatty acyl chain, in the position of the fluorescence group, and in the attached fluorescence moiety (7-nitrobenz-2-oxa-1,3-diazol-4-yl (NBD) or dipyrrometheneboron difluoride (BODIPY)). In aqueous buffer, cyclodextrins bind fluorescent lipids disturbing the organization of the analogs. When incorporated into lipid vesicles, analogs are selectively extracted from the membrane upon addition of cyclodextrins. The results show that the interaction of cyclodextrins with fluorescent phospholipids depends on the cyclodextrin species, the fluorescence moiety and the phospholipid structure. The presented data should be of interest for studies using fluorescent phospholipids and cyclodextrins, since the interaction between the fluorescence group and the cyclodextrin may interfere with the process(es) under study.

  17. Degradation of cholesterol crystals in phospholipids

    Science.gov (United States)

    Koren, Eugen; Koscec, Mirna; Fugate, Robert D.

    1993-02-01

    Based on previous studies from the laboratory that demonstrated degradation of cholesterol crystals ingested by macrophages in a cell culture system and indicated that intracellular phospholipids could play an important role in mobilization of crystalline cholesterol, the role of each of the three major intracellular phospholipid species in degradation of crystals is further explored. Fluorescently labeled cholesterol crystals are incubated with phospholipids over a period of 5 d. Morphological changes in crystals are monitored using digital imaging fluorescence microscopy, fluorescence redistribution after photobleaching, confocal microscopy, and epifluorescent and phase contrast microscopy. Results clearly demonstrate that all three phospholipids are able to mobilize crystalline cholesterol. However, the mechanisms by which they exert mobilization are different. Sphingomyelin and phosphatidylchloline are found to cause gradual and uniform dissolution of crystals, more or less preserving their original shape. Phosphatidylethanolamine appear to penetrate into the crystal, causing its fragmentation and solubilization. In the mixture of all three phospholipids representing the composition found in macrophages, both of the described mechanisms are working simultaneously.

  18. Hybrid, Nanoscale Phospholipid/Block Copolymer Vesicles

    Directory of Open Access Journals (Sweden)

    Bo Liedberg

    2013-09-01

    Full Text Available Hybrid phospholipid/block copolymer vesicles, in which the polymeric membrane is blended with phospholipids, display interesting self-assembly behavior, incorporating the robustness and chemical versatility of polymersomes with the softness and biocompatibility of liposomes. Such structures can be conveniently characterized by preparing giant unilamellar vesicles (GUVs via electroformation. Here, we are interested in exploring the self-assembly and properties of the analogous nanoscale hybrid vesicles (ca. 100 nm in diameter of the same composition prepared by film-hydration and extrusion. We show that the self-assembly and content-release behavior of nanoscale polybutadiene-b-poly(ethylene oxide (PB-PEO/1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine (POPC hybrid phospholipid/block copolymer vesicles can be tuned by the mixing ratio of the amphiphiles. In brief, these hybrids may provide alternative tools for drug delivery purposes and molecular imaging/sensing applications and clearly open up new avenues for further investigation.

  19. Storage stability of marine phospholipids emulsions

    DEFF Research Database (Denmark)

    Lu, Henna Fung Sieng; Nielsen, Nina Skall; Baron, Caroline Pascale

    Marine phospholipids (MPL) are believed to provide more advantages than fish oil from the same source. They are considered to have a better bioavailability, a better resistance towards oxidation and a higher content of polyunsaturated fatty acids such as eicosapentaenoic (EPA) and docosahexaenoic...... of secondary volatile compounds by Solid Phase Microextraction at several time intervals at 2°C storage. Preliminary results showed that marine phospholipids emulsion has a good oxidative stability....... acids (DHA) than oily triglycerides (fish oil). Therefore, the objective of this study is to explore the feasibility of using marine phospholipids emulsions as delivery system through investigation of the physical, oxidative and hydrolytic stability of MPL emulsions with or without addition of fish oil...

  20. Mechanics and dynamics of triglyceride-phospholipid model membranes: Implications for cellular properties and function

    DEFF Research Database (Denmark)

    Pakkanen, Kirsi I.; Duelund, Lars; Qvortrup, Klaus

    2011-01-01

    We demonstrate here that triolein alters the mechanical properties of phospholipid membranes and induces extraordinary conformational dynamics. Triolein containing membranes exhibit fluctuations up to size range of 100µm and with the help of these are e.g. able to squeeze through narrow passages ...

  1. Mechanics and dynamics of triglyceride-phospholipid model membranes: Implications for cellular properties and function

    DEFF Research Database (Denmark)

    Pakkanen, Kirsi I.; Duelund, Lars; Qvortrup, Klaus

    2011-01-01

    We demonstrate here that triolein alters the mechanical properties of phospholipid membranes and induces extraordinary conformational dynamics. Triolein containing membranes exhibit fluctuations up to size range of 100µm and with the help of these are e.g. able to squeeze through narrow passages ...

  2. Guide to good practices for operations turnover

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1998-12-01

    This Guide to Good Practices is written to enhance understanding of, and provide direction for, Operations Turnover, Chapter XII of Department of Energy (DOE) Order 5480.19, Conduct of Operations Requirements for DOE Facilities. The practices in this guide should be considered when planning or reviewing operations turnover programs. Contractors are advised to adopt procedures that meet the intent of DOE Order 5480.19. Operations Turnover is an element of an effective Conduct of Operations program. The complexity and array of activities performed in DOE facilities dictate the necessity for a formal operations turnover program to promote safe and efficient operations.

  3. The costs of turnover in nursing homes

    Science.gov (United States)

    Mukamel, Dana B.; Spector, William D.; Limcangco, Rhona; Wang, Ying; Feng, Zhanlian; Mor, Vincent

    2009-01-01

    Background Turnover rates in nursing homes have been persistently high for decades, ranging upwards of 100%. Objectives To estimate the net costs associated with turnover of direct care staff in nursing homes. Data and sample 902 nursing homes in California in 2005. Data included Medicaid cost reports, the Minimum Data Set (MDS), Medicare enrollment files, Census and Area Resource File (ARF). Research Design We estimated total cost functions, which included in addition to exogenous outputs and wages, the facility turnover rate. Instrumental variable (IV) limited information maximum likelihood techniques were used for estimation to deal with the endogeneity of turnover and costs. Results The cost functions exhibited the expected behavior, with initially increasing and then decreasing returns to scale. The ordinary least square estimate did not show a significant association between costs and turnover. The IV estimate of turnover costs was negative and significant (p=0.039). The marginal cost savings associated with a 10 percentage point increase in turnover for an average facility was $167,063 or 2.9% of annual total costs. Conclusion The net savings associated with turnover offer an explanation for the persistence of this phenomenon over the last decades, despite the many policy initiatives to reduce it. Future policy efforts need to recognize the complex relationship between turnover and costs. PMID:19648834

  4. The costs of turnover in nursing homes.

    Science.gov (United States)

    Mukamel, Dana B; Spector, William D; Limcangco, Rhona; Wang, Ying; Feng, Zhanlian; Mor, Vincent

    2009-10-01

    Turnover rates in nursing homes have been persistently high for decades, ranging upwards of 100%. To estimate the net costs associated with turnover of direct care staff in nursing homes. DATA AND SAMPLE: Nine hundred two nursing homes in California in 2005. Data included Medicaid cost reports, the Minimum Data Set, Medicare enrollment files, Census, and Area Resource File. We estimated total cost functions, which included in addition to exogenous outputs and wages, the facility turnover rate. Instrumental variable limited information maximum likelihood techniques were used for estimation to deal with the endogeneity of turnover and costs. The cost functions exhibited the expected behavior, with initially increasing and then decreasing returns to scale. The ordinary least square estimate did not show a significant association between costs and turnover. The instrumental variable estimate of turnover costs was negative and significant (P = 0.039). The marginal cost savings associated with a 10% point increase in turnover for an average facility was $167,063 or 2.9% of annual total costs. The net savings associated with turnover offer an explanation for the persistence of this phenomenon over the last decades, despite the many policy initiatives to reduce it. Future policy efforts need to recognize the complex relationship between turnover and costs.

  5. Separation and identification of phospholipid peroxidation products.

    Science.gov (United States)

    Milne, G L; Porter, N A

    2001-11-01

    The molecular species in mixtures of phospholipid hydroperoxides are difficult to separate and identify by typical chromatographic and mass spectrometric techniques. As reported by Havrilla and coworkers, silver ion coordination ion-spray mass spectrometry (CIS-MS) has proven to be a powerful technique for the identification of mixtures of hydroperoxides. This ionization technique, which involves the formation of Ag+ adducts of the hydroperoxides, provides valuable, unambiguous structural information about the hydroperoxides. Herein, we report a method for the analysis and identification of phospholipid hydroperoxides using CIS-MS. We also report an improved method for the separation of phospholipid hydroperoxides by reversed-phase high-performance liquid chromatography (RP-HPLC), which, for the first time, separates some of the hydroperoxide isomers. CIS-MS can be coupled with this RP-HPLC method by the addition of AgBF4 to the mobile phase or to the HPLC effluent postcolumn, thus allowing powerful HPLC-MS techniques to be used to identify complex mixtures of phospholipid hydroperoxides.

  6. Pseudocritical Behavior and Unbinding of Phospholipid Bilayers

    DEFF Research Database (Denmark)

    Lemmich, Jesper; Mortensen, Kell; Ipsen, John Hjorth;

    1995-01-01

    The temperature dependence of the small-angle neutron scattering from fully hydrated multilamellar phospholipid bilayers near the main phase transition is analyzed by means of a simple geometric model which yields both the lamellar repeat distance as well as the hydrophobic thickness of the bilayer...

  7. Computer simulations of phospholipid - membrane thermodynamic fluctuations

    DEFF Research Database (Denmark)

    Pedersen, U.R.; Peters, Günther H.j.; Schröder, T.B.

    2008-01-01

    This paper reports all-atom computer simulations of five phospholipid membranes, DMPC, DPPC, DMPG, DMPS, and DMPSH, with a focus on the thermal equilibrium fluctuations of volume, energy, area, thickness, and order parameter. For the slow fluctuations at constant temperature and pressure (defined...

  8. The effect of N-stearoylethanolamine on liver phospholipid composition of rats with insulin resistance caused by alimentary obesity

    Directory of Open Access Journals (Sweden)

    O. V. Onopchenko

    2014-02-01

    Full Text Available We used alimentary obesity-induced insulin resistance (IR model in rats to investigate the influence of N-stearoylethanolamine on the content of phospholipids and their fatty acid composition. Our results show that prolonged high-fat diet triggers considerable aberrations in the composition of main phospholipids in the liver and can be one of the causes of IR in rats. In particular, the increase of phosphatidylcholine, phosphatidylethanolamine and significant decrease of other phospholipids: lysophosphatidylcholine, lysophosphatidylethanolamine, sphingomyelin, phosphatidylinositol, phosphatidylserine and diphosphaglicerol were observed. The levels of monounsaturated (erucic, nervonic, oleic and polyunsaturated (eicosatrienoic, docosatrienoic, arachidonic fatty acids were increased; meanwhile the content of diunsaturated acids was decreased. The NSE administration (50 mg/kg of body weight caused restoration of the phospholipids content in the liver of rats with diet-induced IR that highly correlated with the decrease in plasma insulin level and the improvement of insulin sensitivity. Moreover, the effect of NSE was accompanied by the normalization of fatty acids composition of phospholipids that could be related to modulating influen­ce of NSE on the activity of the main fatty acid desaturases. It is known that the imbalance in phospholipid composition of the rat liver causes substantial metabolic alterations that are associated with the development of IR. Accordingly, the compensations of the imbalance by NSE can help to restore insulin sensitivity, inhibit the development of obesity, IR and type 2 diabetes.

  9. Blood clotting reactions on nanoscale phospholipid bilayers.

    Science.gov (United States)

    Morrissey, James H; Pureza, Vincent; Davis-Harrison, Rebecca L; Sligar, Stephen G; Ohkubo, Y Zenmei; Tajkhorshid, Emad

    2008-01-01

    Blood clotting reactions, such as those catalyzed by the tissue factor:factor VIIa complex (TF:FVIIa), assemble on membrane surfaces containing anionic phospholipids such as phosphatidylserine (PS). In fact, membrane binding is critical for the function of most of the steps in the blood clotting cascade. In spite of this, our understanding of how the membrane contributes to catalysis, or even how these proteins interact with phospholipids, is incomplete. Making matters more complicated, membranes containing mixtures of PS and neutral phospholipids are known to spontaneously form PS-rich membrane microdomains in the presence of plasma concentrations of calcium ions, and it is likely that blood-clotting proteases such as TF:FVIIa partition into these PS-rich microdomains. Unfortunately, little is known about how membrane microdomain composition influences the activity of blood-clotting proteases, which is typically not under experimental control even in "simple" model membranes. Our laboratories have developed and applied new technologies for studying membrane proteins to gain insights into how blood-clotting protease-cofactor pairs assemble and function on membrane surfaces. This includes using a novel, nanoscale bilayer system (Nanodiscs) that permits assembling blood-clotting protease-cofactor pairs on stable bilayers containing from 65 to 250 phospholipid molecules per leaflet. We have used this system to investigate how local (nanometer-scale) changes in phospholipid bilayer composition modulate TF:FVIIa activity. We have also used detailed molecular-dynamics simulations of nanoscale bilayers to provide atomic-scale predictions of how the membrane-binding domain of factor VIIa interacts with PS in membranes.

  10. Synthesis and function of phospholipids in Staphylococcus aureus.

    Science.gov (United States)

    Kuhn, Sebastian; Slavetinsky, Christoph J; Peschel, Andreas

    2015-02-01

    Phospholipids are the major components of bacterial membranes, and changes in phospholipid composition affect important cellular processes such as metabolism, stress response, antimicrobial resistance, and virulence. The most prominent phospholipids in Staphylococcus aureus are phosphatidylglycerol, lysyl-phosphatidylglycerol, and cardiolipin, whose biosynthesis is mediated by a complex protein machinery. Phospholipid composition of the staphylococcal membrane has to be continuously adjusted to changing external conditions, which is achieved by a series of transcriptional and biochemical regulatory mechanisms. This mini-review outlines the current state of knowledge concerning synthesis, regulation, and function of the major staphylococcal phospholipids.

  11. Structure and organization of phospholipid/polysaccharide nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Gerelli, Y; Bari, M T Di; Deriu, A [Dipartimento di Fisica and CNISM, Universita degli Studi di Parma and CRS SOFT, INFM-CNR (Italy); Cantu, L [Dipartimento di Chimica, Biochimica e Biotecnologie per la Medicina-LITA, Universita di Milano (Italy); Colombo, P; Como, C; Motta, S; Sonvico, F [Dipartimento Farmaceutico, Universita degli Studi di Parma (Italy); May, R [Institut Laue-Langevin, Grenoble (France)], E-mail: Antonio.Deriu@fis.unipr.it

    2008-03-12

    In recent years nanoparticles and microparticles composed of polymeric or lipid material have been proposed as drug carriers for improving the efficacy of encapsulated drugs. For the production of these systems different materials have been proposed, among them phospholipids and polysaccharides due to their biocompatibility, biodegradability, low cost and safety. We report here a morphological and structural investigation, performed using cryo-TEM, static light scattering and small angle neutron and x-ray scattering, on phospholipid/saccharide nanoparticles loaded with a lipophilic positively charged drug (tamoxifen citrate) used in breast cancer therapy. The lipid component was soybean lecithin; the saccharide one was chitosan that usually acts as an outer coating increasing vesicle stability. The microscopy and scattering data indicate the presence of two distinct nanoparticle families: uni-lamellar vesicles with average radius 90 A and multi-lamellar vesicles with average radius 440 A. In both families the inner core is occupied by the solvent. The presence of tamoxifen gives rise to a multi-lamellar structure of the lipid outer shell. It also induces a positive surface charge into the vesicles, repelling the positively charged chitosan molecules which therefore do not take part in nanoparticle formation.

  12. Influence of silybin on biophysical properties of phospholipid bilayers

    Institute of Scientific and Technical Information of China (English)

    Olga WESO(L)OWSKA; Krystyna MICHALAK; Barbara (L)ANIA-PIETRZAK; Micha(l) KU(Z)D(Z)A(L); Kamila STA(N)CZAK; Daniela MOSI(A)DZ; Piotr DOBRYSZYCKI; Andrzej O(Z)YHAR; Ma(l)gorzata KOMOROWSKA; Andrzej B HENDRICH

    2007-01-01

    Aim: Silybin (silibinin)is major biologically active flavonolignan extracted from milk thistle (Sylibum marianum). Its biological activities include hepato-protection, anticancer properties, and antioxidant- and membrane-stabilizing functions. Al-though membranes are postulated to be one of the cellular targets for silybin, little is known about its interaction with phospholipid bilayers. Methods: In the present work, the interactions of silybin with phosphatidylcholine bilayers were studied in detail using fluorescence spectroscopy, microcalorimetry and electron spin resonance techniques. Results: The results showed that silybin interacted with the surface of lipid bilayers. It affected the generalized polarization of the fluores-cent probe Prodan, while not influencing the more deeplylocated Laurdan. Silybin lowered the main phospholipid phase transition temperature as judged by microcalorimetry, and caused the immobilization of spin probe Tempo-palmitate located on the surface of membranes. The mobility of spin probes 5-and 16-doxylstearic acid was not affected by silybin. Silybin-induced quenching of 1,6-diphe-nyl-1,3,5-hexatriene fluorescence indicated that some flavonoid molecules parti-tioned into the hydrophobic region of membranes, which did not change signifi-cantly the biophysical properties of the deeper membrane regions. Conclusion: Such a behavior of silybin in membranes is in accordance with its postulated biological functions and neglectable side effects of therapies using silybin.

  13. Metformin Decouples Phospholipid Metabolism in Breast Cancer Cells.

    Directory of Open Access Journals (Sweden)

    Tim A D Smith

    Full Text Available The antidiabetic drug metformin, currently undergoing trials for cancer treatment, modulates lipid and glucose metabolism both crucial in phospholipid synthesis. Here the effect of treatment of breast tumour cells with metformin on phosphatidylcholine (PtdCho metabolism which plays a key role in membrane synthesis and intracellular signalling has been examined.MDA-MB-468, BT474 and SKBr3 breast cancer cell lines were treated with metformin and [3H-methyl]choline and [14C(U]glucose incorporation and lipid accumulation determined in the presence and absence of lipase inhibitors. Activities of choline kinase (CK, CTP:phosphocholine cytidylyl transferase (CCT and PtdCho-phospholipase C (PLC were also measured. [3H] Radiolabelled metabolites were determined using thin layer chromatography.Metformin-treated cells exhibited decreased formation of [3H]phosphocholine but increased accumulation of [3H]choline by PtdCho. CK and PLC activities were decreased and CCT activity increased by metformin-treatment. [14C] incorporation into fatty acids was decreased and into glycerol was increased in breast cancer cells treated with metformin incubated with [14C(U]glucose.This is the first study to show that treatment of breast cancer cells with metformin induces profound changes in phospholipid metabolism.

  14. Can transformational managers control turnover intention?

    Directory of Open Access Journals (Sweden)

    Massad A. Alatawi

    2017-01-01

    Full Text Available Orientation and research purpose: Employee turnover is a complex phenomenon that has negative consequences for organisations. The purpose of this study was to measure the correlation between transformational leadership style and turnover intention to control the employee turnover rate in organisations.Research method: This study utilised a two-stage clustering method and web-based survey research with a correlational design to collect the data. A total of 356 responses were collected from 14 clusters in Southern California; however, the final selected data for analysis came from 210 subjects with a cluster-sampling design of (14 × 15.Main findings and managerial implications: This study concluded that the transformational leadership style has a negative correlation with turnover intention. Managers who adopt this style of leadership can expect lower rates of turnover; thus, they can stay competitive in an unstable economy and achieve enhanced productivity, improved performance and reduction in expenses.

  15. Predictors of turnover intention in nurse faculty.

    Science.gov (United States)

    Gormley, Denise K; Kennerly, Susan

    2011-04-01

    Turnover of nurse faculty is an increasingly important issue in nursing as the available number of qualified faculty continues to decrease. Understanding the factors that contribute to turnover is important to academic administrators to retain and recruit qualified nursing faculty. The purpose of this study was to examine predictors of turnover intention in nurse faculty working in departments and schools of nursing in Carnegie Doctoral/Research Universities-Extensive, public and private, not-for-profit institutions. The multidimensional model of organizational commitment was used to frame this study. The predictor variables explored were organizational climate, organizational commitment, work role balance, role ambiguity, and role conflict. The work roles examined were research, teaching, and service. Logistical regression was performed to examine the predictors of turnover intention. Organizational climate intimacy and disengagement, affective and continuance organizational commitment, and role ambiguity were shown to predict turnover intention in nurse faculty. Copyright 2011, SLACK Incorporated.

  16. Chronic Teacher Turnover in Urban Elementary Schools

    Directory of Open Access Journals (Sweden)

    Kacey Guin

    2004-08-01

    Full Text Available This study examines the characteristics of elementary schools that experience chronic teacher turnover and the impacts of turnover on a school’s working climate and ability to effectively function. Based on evidence from staff climate surveys and case studies, it is clear that high turnover schools face significant organizational challenges. Schools with high teacher turnover rates have difficulty planning and implementing a coherent curriculum and sustaining positive working relationships among teachers. The reality of these organizational challenges is particularly alarming, given that high turnover schools are more likely to serve low-income and minority students. The negative relationship between teacher turnover and school functioning, and the fact that turbulent schools are disproportionately likely to serve lowincome and minority students have important implications for both district and school-level policies. Specifically: Teacher turnover rates are one indicator of school health, which school districts should consider when focusing on school improvements. Districts need to begin by developing the means to identify individual schools that experience high levels of teacher turnover. Current district policies in implementing professional development for teachers in low-performing schools are inefficient when teachers do not remain in the schools in which they are trained. In order for low-performing schools to improve, districts need to consider providing incentive programs so that high quality teachers apply for, and remain in, these schools. Future research is needed to address the causal link between turnover, organizational functioning and student outcomes. Additionally, there is a need for research examining district policies that may facilitate teacher turnover within a district, including how districts place and transfer teachers, as well as how teachers’ salaries are budgeted.

  17. Inhibition of keratinocyte proliferation by phospholipid-conjugates of a TLR7 ligand in a Myc-induced hyperplastic actinic keratosis model in the absence of systemic side effects

    Science.gov (United States)

    CRAIN, Brian; YAO, Shiyin; KEOPHILAONE, Vina; PROMESSI, Victor; KANG, McNancy; BARBERIS, Alcide; MAJ, Roberto; MURA, Emanuela; PASSINI, Nadia; HOLLDACK, Johanna; OCHOA, Ricardo; COTTAM, Howard B.; CARSON, Dennis A.; HAYASHI, Tomoko

    2014-01-01

    Background The Toll-like receptor 7 (TLR7) activator imiquimod (IMQ) is safe and effective in treating actinic keratosis; however, an intermittent treatment regimen is necessary because of excessive local reactions. Objectives To evaluate in vitro potency, pharmacodynamics/pharmacokinetics, toxicity and efficacy in vivo of the newly developed TLR7 ligand-phospholipid conjugate, TMX-202, in a gel formulation. Material and Methods The effects of TMX-202 were assessed both in vitro on a murine macrophage cell line and in primary bone marrow-derived dendritic cells and in vivo on mice (C57BL/6-wild type, Myd88−/− and Tlr7−/−). Results TMX-202 was more potent than IMQ in vitro using murine and human cells. In contrast, in vivo it showed less systemic pro-inflammatory activity and better safety than IMQ. Moreover, the TMX-202 gel formulation exhibited at least comparable efficacy to Aldara in a mouse model for skin proliferative diseases. Conclusion TMX-202 is safe and efficacious without causing excessive adverse effects, suggesting that it may be an alternative to Aldara for the treatment of proliferative skin conditions. PMID:24225049

  18. Slow Phospholipid Exchange between a Detergent-Solubilized Membrane Protein and Lipid-Detergent Mixed Micelles Brominated Phospholipids as Tools to Follow Its Kinetics

    DEFF Research Database (Denmark)

    Montigny, Cédric; Dieudonné, Thibaud; Orlowski, Stéphane

    2017-01-01

    Membrane proteins are largely dependent for their function on the phospholipids present in their immediate environment, and when they are solubilized by detergent for further study, residual phospholipids are critical, too. Here, brominated phosphatidylcholine, a phospholipid which behaves as an ...

  19. Interaction of isopropylthioxanthone with phospholipid liposomes.

    Science.gov (United States)

    Momo, Federico; Fabris, Sabrina; Stevanato, Roberto

    2007-04-01

    Isopropylthioxanthone (ITX) is a highly lipophilic molecule which can be released in foods and beverages from the packages, where it is present as photoinitiator of inks in printing processes. Recently it was found in babies milk, and its toxicity cannot be excluded. The structure of the molecule suggests a possible strong interaction with the lipid moiety of biological membranes, and this is the first study of its effects on phospholipid organization, using differential scanning calorimetry (DSC) and spin labelling techniques. The data obtained with multilamellar liposomes of saturated phospholipids of different length, with and without cholesterol, point out that the molecule changes the lipid structure; in particular, in the gel state, behaving like a disordering agent it increases the mobility of the bilayer, while, in the fluid state, tends to rigidify the membrane, in a cholesterol like way. This behavior supports the hypothesis that ITX experiences a relocation process when the lipid matrix passes from the gel to the fluid state.

  20. Planar bilayer membranes from photoactivable phospholipids.

    Science.gov (United States)

    Borle, F; Sänger, M; Sigrist, H

    1991-07-22

    Planar bilayer membranes formed from photoactivable phospholipids have been characterized by low frequency voltametry. Cyclic voltametric measurements were applied for simultaneous registration of planar membrane conductivity and capacitance. The procedure has been utilized to characterize the formation and stability of planar bilayer membranes. Bilayer membranes were formed from N'-(1,2-dimyristoyl-sn-glycero-3-phosphoethyl)-N-((m-3- trifluoromethyldiazirine)phenyl)thiourea (C14-PED), a head-group photosensitive phospholipid. In situ photoactivation of C14-PED at wavelengths greater than or equal to 320 nm altered neither the mean conductivity nor the capacitance of the bilayer. Ionophore (valinomycin) and ion channel (gramicidin) activities were not impaired upon photoactivation. In contrast, bilayer membranes formed from 1,2-bis(hexadeca-2,4-dienoyl)-sn- glycero-3-phosphocholine (C16-DENPC) revealed short life times. In situ photopolymerization of the diene fatty acids significantly increased the membrane conductivity or led to membrane rupture.

  1. Molecular phospholipid films on solid supports

    DEFF Research Database (Denmark)

    Czolkos, Ilja; Jesorka, Aldo; Orwar, Owe

    2011-01-01

    Phospholipid membranes are versatile structures for mimicking biological surfaces. Bilayer and monolayer membranes can be formed on solid supports, leading to enhanced stability and accessibility of the biomimetic molecular film. This has facilitated functional studies of membrane proteins...... stable lipid membranes. In this review, the current state of the art of molecularly thin lipid layer fabrication is presented with an emphasis on support materials, film formation mechanisms, characterisation methods, and applications....

  2. Phospholipids as Biomarkers for Excessive Alcohol Use

    Science.gov (United States)

    2016-10-01

    is designed to evaluate the utility of levels of two phospholipids in serum as a marker of past drinking behavior across month- level time horizons...in an attempt to improve ability to measure alcohol quantity consumed and associated damage better than can be done with ethyl alcohol level measures...and other existing tests that only measure very recent exposure and poorly reflect quantity consumed . This will be achieved by correlating detailed

  3. Annexin-Phospholipid Interactions. Functional Implications

    Directory of Open Access Journals (Sweden)

    Javier Turnay

    2013-01-01

    Full Text Available Annexins constitute an evolutionary conserved multigene protein superfamily characterized by their ability to interact with biological membranes in a calcium dependent manner. They are expressed by all living organisms with the exception of certain unicellular organisms. The vertebrate annexin core is composed of four (eight in annexin A6 homologous domains of around 70 amino acids, with the overall shape of a slightly bent ring surrounding a central hydrophilic pore. Calcium- and phospholipid-binding sites are located on the convex side while the N-terminus links domains I and IV on the concave side. The N-terminus region shows great variability in length and amino acid sequence and it greatly influences protein stability and specific functions of annexins. These proteins interact mainly with acidic phospholipids, such as phosphatidylserine, but differences are found regarding their affinity for lipids and calcium requirements for the interaction. Annexins are involved in a wide range of intra- and extracellular biological processes in vitro, most of them directly related with the conserved ability to bind to phospholipid bilayers: membrane trafficking, membrane-cytoskeleton anchorage, ion channel activity and regulation, as well as antiinflammatory and anticoagulant activities. However, the in vivo physiological functions of annexins are just beginning to be established.

  4. Empirical Prediction of Turnovers in NFL Football

    Directory of Open Access Journals (Sweden)

    Joel R. Bock

    2016-12-01

    Full Text Available Turnovers in the National Football League (NFL occur whenever a team loses possession of the ball due to a fumble, or an interception. Turnovers disrupt momentum of the offensive team, and represent lost opportunities to advance downfield and score. Teams with a positive differential turnover margin in a given game win 70 % of the time. Turnovers are statistically rare events, occurring apparently randomly. These characteristics make them difficult to predict. This investigation advances the hypothesis that turnovers are predictable in NFL football. Machine learning models are developed to learn the concept: At any point within a football game, what is the likelihood that a turnover will be observed on the next play from scrimmage? NFL play-by-play data for 32 teams spanning seven full seasons were used to train the models. Results presented suggest evidence to support the working hypothesis. Under certain conditions, both fumbles and interceptions can be anticipated at low false discovery rates (less than 15 % . When a turnover is predicted on the impending play from scrimmage, a high degree of confidence is associated with that prediction. The ability to anticipate catastrophic in-game events may lead to their management and control, ultimately improving the performance of individual athletes and their teams. This investigation contributes to the sports science literature by demonstrating the predictability of in-game events often considered to be essentially random in their occurrence. To the author’s knowledge, direct prediction of turnovers has not previously appeared in the literature, which has focused on retrospective statistical analyses of turnover margin in football games.

  5. Nursing home spending, staffing, and turnover.

    Science.gov (United States)

    Kash, Bita A; Castle, Nicholas G; Phillips, Charles D

    2007-01-01

    Recent work on nursing home staffing and turnover has stressed the importance of ownership and resources. However, few studies have examined spending behaviors, which might also influence staffing levels and staff turnover rates. This study investigates whether spending behaviors measured by financial ratios are associated with staffing levels and staff turnover in nursing homes. We analyzed cross-sectional data from 1,014 Texas homes. Data were from the 2002 Texas Nursing Facility Medicaid Cost Report and the 2003 Area Resource File. First, we examined differences in financial ratios by ownership type. Next, the effect of 10 financial ratios on staffing levels and turnover rates for registered nurses, licensed vocational nurses, and certified nursing assistants was examined using robust regression models. Descriptive data indicated that expense ratios related to resident care activities and staff development were significantly higher among not-for-profit than for-profit homes. Higher profits were associated with lower staffing levels, but not higher turnover rates. Administrative expenses (a measure of management capacity) had a negative impact both on staffing levels and staff turnover for licensed vocational nurses and certified nursing assistants, but they did not affect registered nurse staffing. Employee benefit expenses exhibited a positive impact on registered nurse and licensed vocational nurse staffing levels. The addition of information on financial ratios to models predicting staffing indicators reduced the effect of ownership on these indicators. Solutions to the staffing and turnover problem should focus on more effective management practices. Certain levels of administrative and staff benefit expenses may be necessary to improve professional staff recruitment and reduce both staffing and turnover costs. Differences in these financial ratios may partially explain the role played by ownership in determining staffing levels and turnover.

  6. Hepatic Bel-7402 Cell Proliferation on Different Phospholipid Surfaces

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    Phospholipids are believed to be important biomaterials.However, limited information is available on their cytocompatibilities.The objective of this study is to evaluate the effects of different phospholipids on the proliferation of hepatic Bel-7402 cells by comparing the adhesion, viability and proliferation of Bel-7402 cells cultured on different phospholipid surfaces.The cell adhesion, determined by counting the number of adhered cells to the surface, indicated that the cell adhesion was enhanced on charged phospolipid membranes.The cell viability evaluated by MTT[3 (4,5-dimethylthiazole-2-yl)-2,5-diphenyl tetrazolium-bromide] showed that cells cultured on charged phospholipids have greater viability than those cultured on the control, while cells cultured on neutral phospholipids showed lower viability.The cell cycle analysis using flow cytometry demonstrated that S phase entry increased on charged phospholipids, while S phase entry decreased on neutral phospholipids.The results suggested that charged phospholipids, especially positively charged phospholipids, show better cytocompatibilities than neutral phospholipids to hepatic Bel-7402 cell.

  7. The validation of the turnover intention scale

    Directory of Open Access Journals (Sweden)

    Chris F.C. Bothma

    2013-01-01

    Full Text Available Orientation: Turnover intention as a construct has attracted increased research attention in the recent past, but there are seemingly not many valid and reliable scales around to measure turnover intention.Research purpose: This study focused on the validation of a shortened, six-item version of the turnover intention scale (TIS-6.Motivation for the study: The research question of whether the TIS-6 is a reliable and a valid scale for measuring turnover intention and for predicting actual turnover was addressed in this study.Research design, approach and method: The study was based on a census-based sample (n= 2429 of employees in an information, communication and technology (ICT sector company (N= 23 134 where the TIS-6 was used as one of the criterion variables. The leavers (those who left the company in this sample were compared with the stayers (those who remained in the employ of the company in this sample in respect of different variables used in the study.Main findings: It was established that the TIS-6 could measure turnover intentions reliably (α= 0.80. The TIS-6 could significantly distinguish between leavers and stayers (actual turnover, thereby confirming its criterion-predictive validity. The scale also established statistically significant differences between leavers and stayers in respect of a number of the remaining theoretical variables used in the study, thereby also confirming its differential validity. These comparisons were conducted for both the 4-month and the 4-year period after the survey was conducted.Practical/managerial implications: Turnover intention is related to a number of variables in the study which necessitates a reappraisal and a reconceptualisation of existing turnover intention models.Contribution/value-add: The TIS-6 can be used as a reliable and valid scale to assess turnover intentions and can therefore be used in research to validly and reliably assess turnover intentions or to

  8. AN ECONOMETRIC APPROACH ABOUT VOLUNTARY TURNOVER

    Directory of Open Access Journals (Sweden)

    ADALET EREN

    2013-06-01

    Full Text Available This study analyzes individual and organizational variables that affect voluntary turnover are determined in the special defence and security companies. A binomial logistic regression model is used to estimate voluntary turnover.  Binomial Logistic regression, reliability test (scale alfa, variance (ANOVA, Post-hoc/Tukey, correlation (Pearson and other basic statistical techniques  with SPSS 13 statistical packet program was used in the analyzes ofresearch data. The study finds that; situation of suppose working, number of child, number of death child, number of home’s moving, support of rent, total monthly income of household, last work’s region, number of prizes, affect voluntary turnover are determined.

  9. Improvements to Kramers Turnover Theory

    CERN Document Server

    Pollak, Eli

    2013-01-01

    The Kramers turnover problem, that is obtaining a uniform expression for the rate of escape of a particle over a barrier for any value of the external friction was solved in the eighties. Two formulations were given, one by Melnikov and Meshkov (MM) (J. Chem. Phys. 85, 1018 (1986)), which was based on a perturbation expansion for the motion of the particle in the presence of friction. The other, by Pollak, Grabert and Haenggi (PGH) (J. Chem. Phys. 91, 4073 (1989)), valid also for memory friction, was based on a perturbation expansion for the motion along the collective unstable normal mode of the particle. Both theories did not take into account the temperature dependence of the average energy loss to the bath. Increasing the bath temperature will reduce the average energy loss. In this paper, we analyse this effect, using a novel perturbation theory. We find that within the MM approach, the thermal energy gained from the bath diverges, the average energy gain becomes infinite, implying an essential failure o...

  10. The longitudinal study of turnover and the cost of turnover in EMS

    Science.gov (United States)

    Patterson, P. Daniel; Jones, Cheryl B.; Hubble, Michael W.; Carr, Matthew; Weaver, Matthew D.; Engberg, John; Castle, Nicholas

    2010-01-01

    Purpose Few studies have examined employee turnover and associated costs in emergency medical services (EMS). The purpose of this study was to quantify the mean annual rate of turnover, total median cost of turnover, and median cost per termination in a diverse sample of EMS agencies. Methods A convenience sample of 40 EMS agencies was followed over a 6 month period. Internet, telephone, and on-site data collection methods were used to document terminations, new hires, open positions, and costs associated with turnover. The cost associated with turnover was calculated based on a modified version of the Nursing Turnover Cost Calculation Methodology (NTCCM). The NTCCM identified direct and indirect costs through a series of questions that agency administrators answered monthly during the study period. A previously tested measure of turnover to calculate the mean annual rate of turnover was used. All calculations were weighted by the size of the EMS agency roster. The mean annual rate of turnover, total median cost of turnover, and median cost per termination were determined for 3 categories of agency staff mix: all paid staff, mix of paid and volunteer (mixed), and all-volunteer. Results The overall weighted mean annual rate of turnover was 10.7%. This rate varied slightly across agency staffing mix: (all-paid=10.2%, mixed=12.3%, all-volunteer=12.4%). Among agencies that experienced turnover (n=25), the weighted median cost of turnover was $71,613.75, which varied across agency staffing mix: (all-paid=$86,452.05, mixed=$9,766.65, and all-volunteer=$0). The weighted median cost per termination was $6,871.51 and varied across agency staffing mix: (all-paid=$7,161.38, mixed=$1,409.64, and all-volunteer=$0). Conclusions Annual rates of turnover and costs associated with turnover vary widely across types of EMS agencies. The study’s mean annual rate of turnover was lower than expected based on information appearing in the news media and EMS trade magazines. Findings

  11. The longitudinal study of turnover and the cost of turnover in emergency medical services.

    Science.gov (United States)

    Patterson, P Daniel; Jones, Cheryl B; Hubble, Michael W; Carr, Matthew; Weaver, Matthew D; Engberg, John; Castle, Nicholas

    2010-01-01

    Few studies have examined employee turnover and associated costs in emergency medical services (EMS). To quantify the mean annual rate of turnover, total median cost of turnover, and median cost per termination in a diverse sample of EMS agencies. A convenience sample of 40 EMS agencies was followed over a six-month period. Internet, telephone, and on-site data-collection methods were used to document terminations, new hires, open positions, and costs associated with turnover. The cost associated with turnover was calculated based on a modified version of the Nursing Turnover Cost Calculation Methodology (NTCCM). The NTCCM identified direct and indirect costs through a series of questions that agency administrators answered monthly during the study period. A previously tested measure of turnover to calculate the mean annual rate of turnover was used. All calculations were weighted by the size of the EMS agency roster. The mean annual rate of turnover, total median cost of turnover, and median cost per termination were determined for three categories of agency staff mix: all-paid staff, mix of paid and volunteer (mixed) staff, and all-volunteer staff. The overall weighted mean annual rate of turnover was 10.7%. This rate varied slightly across agency staffing mix (all-paid = 10.2%, mixed = 12.3%, all-volunteer = 12.4%). Among agencies that experienced turnover (n = 25), the weighted median cost of turnover was $71,613.75, which varied across agency staffing mix (all-paid = $86,452.05, mixed = $9,766.65, and all-volunteer = $0). The weighted median cost per termination was $6,871.51 and varied across agency staffing mix (all-paid = $7,161.38, mixed = $1,409.64, and all-volunteer = $0). Annual rates of turnover and costs associated with turnover vary widely across types of EMS agencies. The study's mean annual rate of turnover was lower than expected based on information appearing in the news media and EMS trade magazines. Findings provide estimates of two key

  12. The herpes simplex virus 1 U{sub S}3 regulates phospholipid synthesis

    Energy Technology Data Exchange (ETDEWEB)

    Wild, Peter, E-mail: pewild@access.uzh.ch [Institute of Veterinary Anatomy, University of Zuerich (Switzerland); Institute of Virology, University of Zuerich (Switzerland); Oliveira, Anna Paula de [Institute of Virology, University of Zuerich (Switzerland); Sonda, Sabrina [Institute for Parasitology, University of Zuerich (Switzerland); Schraner, Elisabeth M. [Institute of Veterinary Anatomy, University of Zuerich (Switzerland); Institute of Virology, University of Zuerich (Switzerland); Ackermann, Mathias; Tobler, Kurt [Institute of Virology, University of Zuerich (Switzerland)

    2012-10-25

    Herpes simplex virus type 1 capsids bud at nuclear and Golgi membranes for envelopment by phospholipid bilayers. In the absence of U{sub S}3, nuclear membranes form multiple folds harboring virions that suggests disturbance in membrane turnover. Therefore, we investigated phospholipid metabolism in cells infected with the U{sub S}3 deletion mutant R7041({Delta}U{sub S}3), and quantified membranes involved in viral envelopment. We report that (i) [{sup 3}H]-choline incorporation into nuclear membranes and cytoplasmic membranes was enhanced peaking at 12 or 20 h post inoculation with wild type HSV-1 and R7041({Delta}U{sub S}3), respectively, (ii) the surface area of nuclear membranes increased until 24 h of R7041({Delta}U{sub S}3) infection forming folds that equaled {approx}45% of the nuclear surface, (iii) the surface area of viral envelopes between nuclear membranes equaled {approx}2400 R7041({Delta}U{sub S}3) virions per cell, and (iv) during R7041({Delta}U{sub S}3) infection, the Golgi complex expanded dramatically. The data indicate that U{sub S}3 plays a significant role in regulation of membrane biosynthesis.

  13. Glycoxidized HDL, HDL enriched with oxidized phospholipids and HDL from diabetic patients inhibit platelet function

    Science.gov (United States)

    Lê, Quang Huy; El Alaoui, Meddy; Véricel, Evelyne; Ségrestin, Bérénice; Soulère, Laurent; Guichardant, Michel; Lagarde, Michel; Moulin, Philippe; Calzada, Catherine

    2015-01-01

    Context High-density lipoproteins (HDL) possess atheroprotective properties including anti-thrombotic and antioxidant effects. Very few studies relate to the functional effects of oxidized HDL on platelets in type 2 diabetes (T2D). Objective The objective of our study was to investigate the effects of in vitro glycoxidized HDL, and HDL from T2D patients on platelet aggregation and arachidonic acid signaling cascade. At the same time, the contents of hydroxylated fatty acids were assessed in HDL. Results Compared to control HDL, in vitro glycoxidized HDL had decreased proportions of linoleic (LA) and arachidonic (AA) acids in phospholipids and cholesteryl esters, and increased concentrations of hydroxy-octadecadienoic acids (9-HODE and 13-HODE) and 15-hydroxy-eicosatetraenoic acid (15-HETE), derived from LA and AA respectively, especially hydroxy derivatives esterified in phospholipids. Glycoxidized HDL dose-dependently decreased collagen-induced platelet aggregation by binding to SR-BI. Glycoxidized HDL prevented collagen-induced increased phosphorylation of platelet p38 MAPK and cytosolic phospholipase A2, as well as intracellular calcium mobilization. HDL enriched with oxidized phospholipids, namely PC(16:0/13-HODE) dose-dependently inhibited platelet aggregation. Increased concentrations of 9-HODE, 13-HODE and 15-HETE in phospholipids (2.1, 2.1 and 2.4-fold increase respectively) were found in HDL from patients with T2D, and these HDL also inhibited platelet aggregation via SR-BI. Conclusions Altogether, our results indicate that in vitro glycoxidized HDL as well as HDL from T2D patients inhibit platelet aggregation, and suggest that oxidized LA-containing phospholipids may contribute to the anti-aggregatory effects of glycoxidized HDL and HDL from T2D patients. PMID:25794249

  14. Empirical Prediction of Turnovers in NFL Football

    National Research Council Canada - National Science Library

    Bock, Joel

    ... are predictable in NFL football. Machine learning models are developed to learn the concept: At any point within a football game, what is the likelihood that a turnover will be observed on the next p...

  15. Phospholipids and protein adaptation of Pseudomonas sp. to the xenoestrogen tributyltin chloride (TBT).

    Science.gov (United States)

    Bernat, Przemysław; Siewiera, Paulina; Soboń, Adrian; Długoński, Jerzy

    2014-09-01

    A tributyltin (TBT)-resistant strain of Pseudomonas sp. isolated from an overworked car filter was tested for its adaptation to TBT. The isolate was checked for organotin degradation ability, as well as membrane lipid and cellular protein composition in the presence of TBT. The phospholipid profiles of bacteria, grown with and without increased amounts of TBT, were characterized using liquid chromatography/electrospray ionization/mass spectrometry. The strain reacted to the biocide by changing the composition of its phospholipids. TBT induced a twofold decline in the amounts of many molecular species of phosphatidylglycerol and an increase in the levels of phosphatidic acid (by 58%) and phosphatidylethanolamine (by 70%). An increase in the degree of saturation of phospholipid fatty acids of TBT exposed Pseudomonas sp. was observed. These changes in the phospholipid composition and concentration reflect the mechanisms which support optimal lipid ordering in the presence of toxic xenobiotic. In the presence of TBT the abundances of 16 proteins, including TonB-dependent receptors, porins and peroxidases were modified, which could indicate a contribution of some enzymes to TBT resistance.

  16. Regulation of endoplasmic reticulum turnover by selective autophagy.

    Science.gov (United States)

    Khaminets, Aliaksandr; Heinrich, Theresa; Mari, Muriel; Grumati, Paolo; Huebner, Antje K; Akutsu, Masato; Liebmann, Lutz; Stolz, Alexandra; Nietzsche, Sandor; Koch, Nicole; Mauthe, Mario; Katona, Istvan; Qualmann, Britta; Weis, Joachim; Reggiori, Fulvio; Kurth, Ingo; Hübner, Christian A; Dikic, Ivan

    2015-06-18

    The endoplasmic reticulum (ER) is the largest intracellular endomembrane system, enabling protein and lipid synthesis, ion homeostasis, quality control of newly synthesized proteins and organelle communication. Constant ER turnover and modulation is needed to meet different cellular requirements and autophagy has an important role in this process. However, its underlying regulatory mechanisms remain unexplained. Here we show that members of the FAM134 reticulon protein family are ER-resident receptors that bind to autophagy modifiers LC3 and GABARAP, and facilitate ER degradation by autophagy ('ER-phagy'). Downregulation of FAM134B protein in human cells causes an expansion of the ER, while FAM134B overexpression results in ER fragmentation and lysosomal degradation. Mutant FAM134B proteins that cause sensory neuropathy in humans are unable to act as ER-phagy receptors. Consistently, disruption of Fam134b in mice causes expansion of the ER, inhibits ER turnover, sensitizes cells to stress-induced apoptotic cell death and leads to degeneration of sensory neurons. Therefore, selective ER-phagy via FAM134 proteins is indispensable for mammalian cell homeostasis and controls ER morphology and turnover in mice and humans.

  17. Neuronal glucoprivation enhances hypothalamic histamine turnover in rats.

    Science.gov (United States)

    Oohara, A; Yoshimatsu, H; Kurokawa, M; Oishi, R; Saeki, K; Sakata, T

    1994-08-01

    Histamine (HA) turnover in the rat hypothalamus following insufficient energy supply due to glucoprivation was examined after administration of insulin or 2-deoxy-D-glucose (2-DG). HA turnover was assessed by accumulation of tele-methylhistamine (t-MH), a major metabolite of brain HA, following administration of pargyline. Intraperitoneal injection of 1, 2, and 4 U/kg of insulin, which had no influence on steady-state levels of HA and t-MH, increased pargyline-induced accumulation of t-MH. Accumulation of t-MH due to pargyline was inversely related to the concomitant plasma glucose concentration after different doses of insulin. The level of t-MH accumulated by pargyline did not change compared with that of controls, when a euglycemic condition was maintained or insulin at a dose of 6 mU per rat was infused into the third cerebroventricle. Intracerebroventricular infusion of 24 mumol per rat of 2-DG, which had no influence on steady-state levels of HA and t-MH, increased the level of t-MH enhanced by pargyline. The results indicate that an increase in hypothalamic HA turnover in response to glucoprivation may be involved in homeostatic regulation of energy metabolism in the brain.

  18. The costs of nurse turnover, part 2: application of the Nursing Turnover Cost Calculation Methodology.

    Science.gov (United States)

    Jones, Cheryl Bland

    2005-01-01

    This is the second article in a 2-part series focusing on nurse turnover and its costs. Part 1 (December 2004) described nurse turnover costs within the context of human capital theory, and using human resource accounting methods, presented the updated Nursing Turnover Cost Calculation Methodology. Part 2 presents an application of this method in an acute care setting and the estimated costs of nurse turnover that were derived. Administrators and researchers can use these methods and cost information to build a business case for nurse retention.

  19. Multi-Reservoir Phospholipid Shell Encapsulating Protamine Nanocapsules for Co-Delivery of Letrozole and Celecoxib in Breast Cancer Therapy.

    Science.gov (United States)

    Elzoghby, Ahmed O; Mostafa, Shaimaa K; Helmy, Maged W; ElDemellawy, Maha A; Sheweita, Salah A

    2017-09-01

    In the current work, we propose a combined delivery nanoplatform for letrozole (LTZ) and celecoxib (CXB). Multi-reservoir nanocarriers were developed by enveloping protamine nanocapsules (PRM-NCs) within drug-phospholipid complex bilayer. Encapsulation of NCs within phospholipid bilayer was confirmed by both size increase from 109.7 to 179.8 nm and reduction of surface charge from +19.0 to +7.78 mV. The multi-compartmental core-shell structure enabled biphasic CXB release with initial fast release induced by complexation with phospholipid shell followed by prolonged release from oily core. Moreover, phospholipid coating provided protection for cationic PRM-NCs against interaction with RBCs and serum proteins enabling their systemic administration. Pharmacokinetic analysis demonstrated prolonged circulation and delayed clearance of both drugs after intravenous administration into rats. The superior anti-tumor efficacy of multi-reservoir NCs was manifested as powerful cytotoxicity against MCF-7 breast cancer cells and marked reduction in the mammary tumor volume in Ehrlich ascites bearing mice compared with free LTZ-CXB combination. Moreover, the NCs induced apoptotic caspase activation and marked inhibition of aromatase expression and angiogenic marker, VEGF as well as inhibition of both NFκB and TNFα. Multi-reservoir phospholipid shell coating PRM-NCs could serve as a promising nanocarrier for parenteral combined delivery of LTZ and CXB.

  20. Huntingtin interactions with membrane phospholipids: strategic targets for therapeutic intervention?

    Science.gov (United States)

    Kegel-Gleason, Kimberly B

    2013-01-01

    The Huntington's disease gene encodes the protein huntingtin (Htt), a soluble protein that largely distributes to the cytoplasm where about half the protein is found in association with membranes. Early studies on Huntington's disease patients suggested changes in membrane phospholipids. Furthermore, changes in phospholipid biosynthetic enzymes have been found in HD cell models using genetic methods. Recent investigations prove that Htt associates with membranes by direct interactions with phospholipids in membranes. Htt contains at least two membrane binding domains, which may work in concert with each other, to target to the appropriate intracellular membranes for diverse functions. Htt has a particular affinity for a specific class of phospholipids called phosphatidylinositol phosphates; individual species of these phospholipids propagate signals promoting cell survival and regulating changes in morphology. Mutant Htt fragments can disrupt synthetic phospholipid bilayers and full-length mutant Htt shows increased binding to numerous phospholipids, supporting the idea that mutant Htt can introduce pathology at the level of phospholipid interactions. There is a great potential to develop therapeutic agents since numerous enzymes regulate the both the biosynthesis/metabolism of lipids and the post-translational modifications of Htt that direct membrane interactions. Understanding the relationship of Htt with membrane phospholipids, and the impact of mutant Htt on membrane-related functions and lipid metabolism, may help identify new modes of therapeutic intervention for Huntington's disease.

  1. Factors Involved in Extracellular Matrix Turnover in Human Derived Cardiomyocytes

    Directory of Open Access Journals (Sweden)

    Gregori Casals

    2013-11-01

    Full Text Available Background: The molecular mechanisms by which myocardial ischemia translates into ventricular remodeling remain unclear. Methods: We investigated whether hypoxia and proinflammatory cytokines are specific inducers of remodeling signals in an in vitro model of cultured adult human ventricular myocytes (AC16 cells. Results:Hypoxia modified the ratio of matrix remodeling factors by increasing the aminoterminal propeptide of type III procollagen (PIIINP and reducing tissue inhibitor of matrix metalloproteinase type 1 (TIMP-1 secretion in AC16 cells. These effects, however, were not associated with either modifications in expression of matrix metalloproteinase type 2, collagen-I or metalloproteinase activity. Hypoxia does, actually increase the production of the cardiac antifibrogenic growth factors, Apelin and VEGF, through an Hypoxia Inducible Factor type 1-dependent mechanism. Concerning proinflammatory signaling pathways, IL1β emerged as a powerful inducer of matrix turnover, since it significantly enhanced PIIINP, TIMP-1 and hyaluronic acid production and increased metalloproteinase activity. In contrast, TNFα did not modify matrix turnover but markedly induced the production of Apelin and VEGF. Conclusion: Hypoxia and increased TNFα activity likely exert cardioprotective actions by activating the cardiac antifibrogenic factors Apelin and VEGF. In contrast, IL1β is a strong promoter of interstitial collagen remodeling that may contribute to ventricular dilation and heart failure in the ischemic myocardium.

  2. Protein-phospholipid interactions in blood clotting.

    Science.gov (United States)

    Morrissey, James H; Davis-Harrison, Rebecca L; Tavoosi, Narjes; Ke, Ke; Pureza, Vincent; Boettcher, John M; Clay, Mary C; Rienstra, Chad M; Ohkubo, Y Zenmei; Pogorelov, Taras V; Tajkhorshid, Emad

    2010-04-01

    Most steps of the blood clotting cascade require the assembly of a serine protease with its specific regulatory protein on a suitable phospholipid bilayer. Unfortunately, the molecular details of how blood clotting proteins bind to membrane surfaces remain poorly understood, owing to a dearth of techniques for studying protein-membrane interactions at high resolution. Our laboratories are tackling this question using a combination of approaches, including nanoscale membrane bilayers, solid-state NMR, and large-scale molecular dynamics simulations. These studies are now providing structural insights at atomic resolution into clotting protein-membrane interactions. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

  3. Motional Coherence in Fluid Phospholipid Membranes

    CERN Document Server

    Rheinstadter, Maikel C; Flenner, Elijah J; Bruening, Beate; Seydel, Tilo; Kosztin, Ioan

    2008-01-01

    We report a high energy-resolution neutron backscattering study, combined with in-situ diffraction, to investigate slow molecular motions on nanosecond time scales in the fluid phase of phospholipid bilayers of 1,2-dimyristoyl-sn-glycero-3-phoshatidylcholine (DMPC) and DMPC/40% cholesterol (wt/wt). A cooperative structural relaxation process was observed. From the in-plane scattering vector dependence of the relaxation rates in hydrogenated and deuterated samples, combined with results from a 0.1 microsecond long all atom molecular dynamics simulation, it is concluded that correlated dynamics in lipid membranes occurs over several lipid distances, spanning a time interval from pico- to nanoseconds.

  4. Hyaluronan and phospholipid association in biolubrication

    DEFF Research Database (Denmark)

    Wang, Min; Liu, Chao; Thormann, Esben

    2013-01-01

    load bearing capacity. With DPPC as the last adsorbed component, a friction coefficient of 0.01 was found up to pressures significantly above what is encountered in healthy synovial joints. Hyaluronan as the last added component increases the friction coefficient to 0.03 and decreases the load bearing...... capacity somewhat (but still above what is needed in the synovial joint). Our data demonstrate that self-assembly structures formed by hyaluronan and phospholipids at interfaces are efficient aqueous lubricants, and it seems plausible that such self-assembly structures contribute to the exceptional...

  5. Addressing employee turnover and retention: keeping your valued performers.

    Science.gov (United States)

    McConnell, Charles R

    2011-01-01

    Employee turnover and employee retention are inextricably linked; to control turnover is to enhance retention. Turnover is a relatively simple concept; however, considerable confusion often results when addressing turnover because of differences in how it is defined; that is, what is counted, how it is counted, and how the turnover rates are expressed. Turnover is also costly, although not enough attention is paid to its cost because so much of it is indirect and thus not readily visible. There are a variety of causes of turnover, some that can be corrected and some that cannot be avoided. Reducing or otherwise controlling turnover requires continuing management attention to its causes and constant recognition of what can and should be controlled and what cannot be controlled. Ongoing attention to turnover is an essential part of the department manager's role; every improvement in turnover is a direct improvement in retention, with eventual positive effects on the bottom line.

  6. Inhibitory effect of some triterpenes from cacti on 32Pi-incorporation into phospholipids of HeLa cells promoted by 12-O-tetradecanoylphorbol-13-acetate.

    Science.gov (United States)

    Kinoshita, K; Yang, Y; Koyama, K; Takahashi, K; Nishino, H

    1999-05-01

    Seventeen triterpenes isolated from cacti and the 10 derivatives were examined for the inhibition of tumor promoter-induced effects in vitro, such as stimulation of 32Pi-incorporation into phospholipids of cultured cells. Betulinic acid (1), cochalic acid (15), erythrodiol (16), oleanolic acid (21) and queretaroic acid (24) inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA) stimulated 32Pi-incorporation into phospholipids of the cultured cells.

  7. A Study On Employee Turnover At Prime Star Fashions, Tirupur

    OpenAIRE

    SHEELAVATHY, R.; HEMALATHA, Mrs.

    2015-01-01

    Employee turnover means number of incoming and outgoing worker from an organization or company. In other words we can say when a new employee takes place of old employee it is called employee turnover in a period of time. The main objective of perusing the study is to assess the main reasons for employee turnover, to know the retention techniques to avoid the employee turnover, to know about the effectiveness of supervising at Prime Star Fashions, Tirupur. The reason for the employee turnover...

  8. A Study On Employee Turnover At Prime Star Fashions, Tirupur

    OpenAIRE

    2015-01-01

    Employee turnover means number of incoming and outgoing worker from an organization or company. In other words we can say when a new employee takes place of old employee it is called employee turnover in a period of time. The main objective of perusing the study is to assess the main reasons for employee turnover, to know the retention techniques to avoid the employee turnover, to know about the effectiveness of supervising at Prime Star Fashions, Tirupur. The reason for the employee turnover...

  9. Protein kinase C interaction with calcium: a phospholipid-dependent process.

    LENUS (Irish Health Repository)

    Bazzi, M D

    1990-08-21

    The calcium-binding properties of calcium- and phospholipid-dependent protein kinase C (PKC) were investigated by equilibrium dialysis in the presence and the absence of phospholipids. Calcium binding to PKC displayed striking and unexpected behavior; the free proteins bound virtually no calcium at intracellular calcium concentrations and bound limited calcium (about 1 mol\\/mol of PKC) at 200 microM calcium. However, in the presence of membranes containing acidic phospholipids, PKC bound at least eight calcium ions per protein. The presence of 1 microM phorbol dibutyrate (PDBu) in the dialysis buffer had little effect on these calcium-binding properties. Analysis of PKC-calcium binding by gel filtration under equilibrium conditions gave similar results; only membrane-associated PKC bound significant amounts of calcium. Consequently, PKC is a member of what may be a large group of proteins that bind calcium in a phospholipid-dependent manner. The calcium concentrations needed to induce PKC-membrane binding were similar to those needed for calcium binding (about 40 microM calcium at the midpoint). However, the calcium concentration required for PKC-membrane binding was strongly influenced by the phosphatidylserine composition of the membranes. Membranes with higher percentages of phosphatidylserine required lower concentrations of calcium. These properties suggested that the calcium sites may be generated at the interface between PKC and the membrane. Calcium may function as a bridge between PKC and phospholipids. These studies also suggested that calcium-dependent PKC-membrane binding and PKC function could be regulated by a number of factors in addition to calcium levels and diacylglycerol content of the membrane.

  10. Tombusviruses upregulate phospholipid biosynthesis via interaction between p33 replication protein and yeast lipid sensor proteins during virus replication in yeast

    Energy Technology Data Exchange (ETDEWEB)

    Barajas, Daniel; Xu, Kai; Sharma, Monika; Wu, Cheng-Yu; Nagy, Peter D., E-mail: pdnagy2@uky.edu

    2014-12-15

    Positive-stranded RNA viruses induce new membranous structures and promote membrane proliferation in infected cells to facilitate viral replication. In this paper, the authors show that a plant-infecting tombusvirus upregulates transcription of phospholipid biosynthesis genes, such as INO1, OPI3 and CHO1, and increases phospholipid levels in yeast model host. This is accomplished by the viral p33 replication protein, which interacts with Opi1p FFAT domain protein and Scs2p VAP protein. Opi1p and Scs2p are phospholipid sensor proteins and they repress the expression of phospholipid genes. Accordingly, deletion of OPI1 transcription repressor in yeast has a stimulatory effect on TBSV RNA accumulation and enhanced tombusvirus replicase activity in an in vitro assay. Altogether, the presented data convincingly demonstrate that de novo lipid biosynthesis is required for optimal TBSV replication. Overall, this work reveals that a (+)RNA virus reprograms the phospholipid biosynthesis pathway in a unique way to facilitate its replication in yeast cells. - Highlights: • Tombusvirus p33 replication protein interacts with FFAT-domain host protein. • Tombusvirus replication leads to upregulation of phospholipids. • Tombusvirus replication depends on de novo lipid synthesis. • Deletion of FFAT-domain host protein enhances TBSV replication. • TBSV rewires host phospholipid synthesis.

  11. Climate change induces shifts in abundance and activity pattern of bacteria and archaea catalyzing major transformation steps in nitrogen turnover in a soil from a mid-European beech forest.

    Directory of Open Access Journals (Sweden)

    Silvia Gschwendtner

    Full Text Available Ongoing climate change will lead to more extreme weather events, including severe drought periods and intense drying rewetting cycles. This will directly influence microbial nitrogen (N turnover rates in soil by changing the water content and the oxygen partial pressure. Therefore, a space for time climate change experiment was conducted by transferring intact beech seedling-soil mesocosms from a northwest (NW exposed site, representing today's climatic conditions, to a southwest (SW exposed site, providing a model climate for future conditions with naturally occurring increased soil temperature (+0.8°C in average. In addition, severe drought and intense rainfall was simulated by a rainout shelter at SW and manual rewetting after 39 days drought, respectively. Soil samples were taken in June, at the end of the drought period (August, 24 and 72 hours after rewetting (August and after a regeneration period of four weeks (September. To follow dynamics of bacterial and archaeal communities involved in N turnover, abundance and activity of nitrifiers, denitrifiers, N2-fixing microbes and N-mineralizers was analyzed based on marker genes and the related transcripts by qPCR from DNA and RNA directly extracted from soil. Abundance of the transcripts was reduced under climate change with most pronounced effects for denitrification. Our results revealed that already a transfer from NW to SW without further treatment resulted in decreased cnor and nosZ transcripts, encoding for nitric oxide reductase and nitrous oxide reductase, respectively, while nirK transcripts, encoding for nitrite reductase, remained unaffected. Severe drought additionally led to reduced nirK and cnor transcripts at SW. After rewetting, nirK transcripts increased rapidly at both sites, while cnor and nosZ transcripts increased only at NW. Our data indicate that the climate change influences activity pattern of microbial communities involved in denitrification processes to a

  12. Climate change induces shifts in abundance and activity pattern of bacteria and archaea catalyzing major transformation steps in nitrogen turnover in a soil from a mid-European beech forest.

    Science.gov (United States)

    Gschwendtner, Silvia; Tejedor, Javier; Bimüller, Carolin; Bimueller, Carolin; Dannenmann, Michael; Kögel-Knabner, Ingrid; Knabner, Ingrid Kögel; Schloter, Michael

    2014-01-01

    Ongoing climate change will lead to more extreme weather events, including severe drought periods and intense drying rewetting cycles. This will directly influence microbial nitrogen (N) turnover rates in soil by changing the water content and the oxygen partial pressure. Therefore, a space for time climate change experiment was conducted by transferring intact beech seedling-soil mesocosms from a northwest (NW) exposed site, representing today's climatic conditions, to a southwest (SW) exposed site, providing a model climate for future conditions with naturally occurring increased soil temperature (+0.8°C in average). In addition, severe drought and intense rainfall was simulated by a rainout shelter at SW and manual rewetting after 39 days drought, respectively. Soil samples were taken in June, at the end of the drought period (August), 24 and 72 hours after rewetting (August) and after a regeneration period of four weeks (September). To follow dynamics of bacterial and archaeal communities involved in N turnover, abundance and activity of nitrifiers, denitrifiers, N2-fixing microbes and N-mineralizers was analyzed based on marker genes and the related transcripts by qPCR from DNA and RNA directly extracted from soil. Abundance of the transcripts was reduced under climate change with most pronounced effects for denitrification. Our results revealed that already a transfer from NW to SW without further treatment resulted in decreased cnor and nosZ transcripts, encoding for nitric oxide reductase and nitrous oxide reductase, respectively, while nirK transcripts, encoding for nitrite reductase, remained unaffected. Severe drought additionally led to reduced nirK and cnor transcripts at SW. After rewetting, nirK transcripts increased rapidly at both sites, while cnor and nosZ transcripts increased only at NW. Our data indicate that the climate change influences activity pattern of microbial communities involved in denitrification processes to a different extend

  13. Predictors of Staff Turnover and Turnover Intentions within Addiction Treatment Settings: Change Over Time Matters

    Science.gov (United States)

    Garner, Bryan R; Hunter, Brooke D

    2014-01-01

    This study examined the extent to which changes over time in clinicians’ responses to measures of work attitude (eg, job satisfaction) and psychological climate (eg, supervisor support) could predict actual turnover and turnover intentions above and beyond absolute levels of these respective measures. Longitudinal data for this study were collected from a sample of clinicians (N = 96) being trained to implement an evidence-based treatment for adolescent substance use disorders. Supporting findings from a recent staff turnover study, we found job satisfaction change was able to predict actual turnover above and beyond average levels of job satisfaction. Representing new contributions to the staff turnover literature, we also found that change over time in several other key measures (eg, job satisfaction, role manageability, role clarity) explained a significant amount of variance in turnover intentions above and beyond the absolute level of each respective measure. A key implication of the current study is that organizations seeking to improve their ability to assess risk for staff turnover may want to consider assessing staff at multiple points in time in order to identify systematic changes in key employee attitudes like turnover intentions and job satisfaction. PMID:25336960

  14. Lithocholic acid disrupts phospholipid and sphingolipid homeostasis leading to cholestasis

    Science.gov (United States)

    Matsubara, Tsutomu; Tanaka, Naoki; Patterson, Andrew D.; Cho, Joo-Youn; Krausz, Kristopher W.; Gonzalez, Frank J.

    2011-01-01

    Lithocholic acid (LCA) is an endogenous compound associated with hepatic toxicity during cholestasis. LCA exposure in mice resulted in decreased serum lysophosphatidylcholine (LPC) and sphingomyelin levels due to elevated lysophosphatidylcholine acyltransferase (LPCAT) and sphingomyelin phosphodiesterase (SMPD) expression. Global metabolome analysis indicated significant decreases in serum palmitoyl-, stearoyl-, oleoyl- and linoleoyl-LPC levels after LCA exposure. LCA treatment also resulted in decreased serum sphingomyelin levels and increased hepatic ceramide levels, and induction of LPCAT and SMPD mRNAs. Transforming growth factor-β TGF-β) induced Lpcat2/4 and Smpd3 gene expression in primary hepatocytes and the induction was diminished by pretreatment with the SMAD3 inhibitor SIS3. Furthermore, alteration of the LPC metabolites and Lpcat1/2/4 and Smpd3 expression was attenuated in LCA-treated farnesoid X receptor-null mice that are resistant to LCA-induced intrahepatic cholestasis. This study revealed that LCA induced disruption of phospholipid/sphingolipid homeostasis through TGF-β signaling and that serum LPC is a biomarker for biliary injury. PMID:21480330

  15. Phospholipid imprinted polymers as selective endotoxin scavengers

    Science.gov (United States)

    Sulc, Robert; Szekely, Gyorgy; Shinde, Sudhirkumar; Wierzbicka, Celina; Vilela, Filipe; Bauer, David; Sellergren, Börje

    2017-03-01

    Herein we explore phospholipid imprinting as a means to design receptors for complex glycolipids comprising the toxic lipopolysaccharide endotoxin. A series of polymerizable bis-imidazolium and urea hosts were evaluated as cationic and neutral hosts for phosphates and phosphonates, the latter used as mimics of the phospholipid head groups. The bis-imidazolium hosts interacted with the guests in a cooperative manner leading to the presence of tight and well defined 1:2 ternary complexes. Optimized monomer combinations were subsequently used for imprinting of phosphatidic acid as an endotoxin dummy template. Presence of the aforementioned ternary complexes during polymerization resulted in imprinting of lipid dimers - the latter believed to crudely mimic the endotoxin Lipid A motif. The polymers were characterized with respect to template rebinding, binding affinity, capacity and common structural properties, leading to the identification of polymers which were thereafter subjected to an industrially validated endotoxin removal test. Two of the polymers were capable of removing endotoxin down to levels well below the accepted threshold (0.005 EU/mg API) in pharmaceutical production.

  16. Low phospholipid-associated cholestasis and cholelithiasis.

    Science.gov (United States)

    Erlinger, Serge

    2012-09-01

    Low phospholipid-associated cholestasis and cholelithiasis (LPAC) is a genetic disorder characterized by cholesterol gallbladder and intrahepatic stones. It is caused by a mutation of the gene ABCB4, which encodes the canalicular protein ABCB4/MDR3, a flippase that plays an essential role in the secretion of phosphatidylcholine into bile. Failure of this protein leads to secretion of bile that is poor in phospholipids and, hence, highly lithogenic, with potent detergent properties. This, in turn, leads to cholangiocyte luminal membrane injury and biliary lesions causing cholestasis. The diagnosis should be suspected when at least two of the following criteria are present: onset of symptoms before the age of 40 years; recurrence of biliary symptoms (biliary colic, jaundice, cholangitis, acute pancreatitis) after cholecystectomy; presence of echogenic foci within the liver indicative of intrahepatic stones or biliary sludge; previous episode(s) of intrahepatic cholestasis of pregnancy; and family history of gallstones in first-degree relatives. Intrahepatic stones can be demonstrated by ultrasonography with color Doppler examination, computed tomography and magnetic resonance imaging with magnetic resonance cholangiography, and the diagnosis confirmed by ABCB4 genotyping. Therapy with ursodeoxycholic acid offers prompt relief of symptoms and usually prevents complications. In some cases, however, surgery may be necessary. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  17. Phospholipid imprinted polymers as selective endotoxin scavengers

    Science.gov (United States)

    Sulc, Robert; Szekely, Gyorgy; Shinde, Sudhirkumar; Wierzbicka, Celina; Vilela, Filipe; Bauer, David; Sellergren, Börje

    2017-01-01

    Herein we explore phospholipid imprinting as a means to design receptors for complex glycolipids comprising the toxic lipopolysaccharide endotoxin. A series of polymerizable bis-imidazolium and urea hosts were evaluated as cationic and neutral hosts for phosphates and phosphonates, the latter used as mimics of the phospholipid head groups. The bis-imidazolium hosts interacted with the guests in a cooperative manner leading to the presence of tight and well defined 1:2 ternary complexes. Optimized monomer combinations were subsequently used for imprinting of phosphatidic acid as an endotoxin dummy template. Presence of the aforementioned ternary complexes during polymerization resulted in imprinting of lipid dimers – the latter believed to crudely mimic the endotoxin Lipid A motif. The polymers were characterized with respect to template rebinding, binding affinity, capacity and common structural properties, leading to the identification of polymers which were thereafter subjected to an industrially validated endotoxin removal test. Two of the polymers were capable of removing endotoxin down to levels well below the accepted threshold (0.005 EU/mg API) in pharmaceutical production. PMID:28303896

  18. Phospholipids as inhibitors of amyloid fibril formation

    Directory of Open Access Journals (Sweden)

    K. O. Vus

    2016-11-01

    Full Text Available Amyloid fibrils are the protein aggregates, whose formation is involved in the pathogenesis of Alzheimer’s disease, systemic amyloidosis, etc. Since there is no effective ways to treat these diseases, developing the new anti-amyloid drugs is of great importance. In this study a series of phospholipids have been tested for their ability to inhibit lysozyme and insulin amyloid fibril formation at acidic or neutral pH and elevated temperature.  The lag time, elongation rate and fibrillization extent were estimated using Thioflavin T fluorescence assay. It is found that the oxidized and charged phospholipids, included into the liposomes, were the most effective inhibitors of the protein fibrillization. By comparing the magnitude and direction of the lipid effect in different lipid-protein systems it was concluded that the reduction of the amyloid fibril formation is governed by hydrophobic and specific liposome-protein interactions. It is hypothesized that the presence of the surface formed by the lipid polar heads is critical for reducing the protein fibrillization extent.

  19. Thin-layer chromatography immunostaining in detecting anti-phospholipid antibodies in seronegative anti-phospholipid syndrome

    Science.gov (United States)

    Conti, F; Alessandri, C; Sorice, M; Capozzi, A; Longo, A; Garofalo, T; Misasi, R; Bompane, D; Hughes, G R V; Khamashta, M A; Valesini, G

    2012-01-01

    In clinical practice it is possible to find patients with clinical signs suggestive of anti-phospholipid syndrome (APS) who are persistently negative for the routinely used anti-phospholipid antibodies (aPL). Therefore, the term proposed for these cases was seronegative APS (SN-APS). We investigated the clinical usefulness of thin-layer chromatography (TLC) immunostaining in detecting serum aPL in patients presenting clinical features of SN-APS. Sera from 36 patients with SN-APS, 19 patients with APS, 18 patients with systemic lupus erythematosus (SLE), 20 anti-hepatitis C virus (HCV)-positive subjects and 32 healthy controls were examined for aPL using TLC immunostaining. Anti-β2-glycoprotein-I, anti-annexin II, anti-annexin V and anti-prothrombin antibodies were tested by enzyme-linked immunosorbent assays (ELISA). Eahy926, a human-derived endothelial cell line, was incubated with immunoglobulin (Ig)G fraction from SN-APS patients and analysis of phospho-interleukin (IL)-1 receptor-associated kinase (IRAK) and phospho-nuclear factor (NF)-κB was performed by Western blot, vascular cell adhesion molecule 1 (VCAM-1) expression by cytofluorimetric analysis and supernatants tissue factor (TF) levels by ELISA. TLC immunostaining showed aPL in 58·3% of SN-APS patients: anti-cardiolipin in 47·2%, anti-lyso(bis)phosphatidic acid in 41·7% and anti-phosphatidylethanolamine in 30·5%. Six of 36 patients showed anti-annexin II. Incubation of Eahy926 cells with IgG from SN-APS induced IRAK phosphorylation, NF-κB activation, VCAM-1 surface expression and TF cell release. TLC immunostaining could identify the presence of aPL in patients with SN-APS. Moreover, the results suggest the proinflammatory and procoagulant effects in vitro of these antibodies. PMID:22288586

  20. Turnover of microbial groups and cell components in soil: 13C analysis of cellular biomarkers

    Science.gov (United States)

    Gunina, Anna; Dippold, Michaela; Glaser, Bruno; Kuzyakov, Yakov

    2017-01-01

    Microorganisms regulate the carbon (C) cycle in soil, controlling the utilization and recycling of organic substances. To reveal the contribution of particular microbial groups to C utilization and turnover within the microbial cells, the fate of 13C-labelled glucose was studied under field conditions. Glucose-derived 13C was traced in cytosol, amino sugars and phospholipid fatty acid (PLFA) pools at intervals of 3, 10 and 50 days after glucose addition into the soil. 13C enrichment in PLFAs ( ˜ 1.5 % of PLFA C at day 3) was an order of magnitude greater than in cytosol, showing the importance of cell membranes for initial C utilization. The 13C enrichment in amino sugars of living microorganisms at day 3 accounted for 0.57 % of total C pool; as a result, we infer that the replacement of C in cell wall components is 3 times slower than that of cell membranes. The C turnover time in the cytosol (150 days) was 3 times longer than in PLFAs (47 days). Consequently, even though the cytosol pool has the fastest processing rates compared to other cellular compartments, intensive recycling of components here leads to a long C turnover time. Both PLFA and amino-sugar profiles indicated that bacteria dominated in glucose utilization. 13C enrichment decreased with time for bacterial cell membrane components, but it remained constant or even increased for filamentous microorganisms. 13C enrichment of muramic acid was the 3.5 times greater than for galactosamine, showing a more rapid turnover of bacterial cell wall components compared to fungal. Thus, bacteria utilize a greater proportion of low-molecular-weight organic substances, whereas filamentous microorganisms are responsible for further C transformations. Thus, tracing 13C in cellular compounds with contrasting turnover rates elucidated the role of microbial groups and their cellular compartments in C utilization and recycling in soil. The results also reflect that microbial C turnover is not restricted to the death or

  1. On gigahertz spectral turnovers in pulsars

    CERN Document Server

    Rajwade, Kaustubh; Anderson, Loren D

    2015-01-01

    Pulsars are known to emit non-thermal radio emission that is generally a power-law function of frequency. In some cases, a turnover is seen at frequencies around 100~MHz. Kijak et al. have reported the presence of a new class of ''Gigahertz Peaked Spectrum'' (GPS) pulsars that show spectral turnovers at frequencies around 1 GHz. We apply a model based on free-free thermal absorption to explain these turnovers in terms of surrounding material such as the dense environments found in HII regions, Pulsar Wind Nebulae (PWNe), or in cold, partially ionized molecular clouds. We show that the turnover frequency depends on the electron temperature of the environment close to the pulsar, as well as the emission measure along the line of sight. We fitted this model to the radio fluxes of known GPS pulsars and show that it can replicate the GHz turnover. From the thermal absorption model, we demonstrate that normal pulsars would exhibit a GPS-like behaviour if they were in a dense environment. We discuss the application ...

  2. Predicting nursing turnover with catastrophe theory.

    Science.gov (United States)

    Wagner, Cheryl M

    2010-09-01

    This paper is a report of a study comparing an innovative nonlinear model and a traditional linear model for accuracy in prediction of nursing turnover. An international, sustained nursing shortage creates a need to target accurately the staff population at risk for turnover. Existing linear methodology is cumbersome with the number of variables needed, while producing inadequate results. Nonlinear modelling methods offer increased simplicity and accuracy in predictability. A correlational survey with a longitudinal cohort prospective study was carried out in 2005-2006 with a convenience sample of 1033 Registered Nurses from the Midwest region of the United States of America. At time 1, 756 usable questionnaires were returned and 496 at time 2. Data analysis included analyses of a cusp catastrophe model, a cube-shaped four-dimensional figure with a top that provided a down-turning slope area (the catastrophe/cusp zone). This fluid, dynamic cusp version employed the smallest number of control and dependent variables. The exceedingly small turnover sample preempted the use of the computerized program Cuspfit; a proven quasi-quantitative methodology demonstrated 80.4% predictability in the cusp catastrophe model overall and 53.6% correct predictions of actual terminations, particularly in nurses with turnover were accurate predictor variables; job tension was not. Catastrophe models are useful in predicting nursing turnover. Future nursing researchers should act on this evidence to benefit forthcoming studies and the profession.

  3. Synthetic phosphoethanolamine induces cell cycle arrest and apoptosis in human breast cancer MCF-7 cells through the mitochondrial pathway.

    Science.gov (United States)

    Ferreira, Adilson Kleber; Meneguelo, Renato; Pereira, Alexandre; Filho, Otaviano Mendonça R; Chierice, Gilberto Orivaldo; Maria, Durvanei Augusto

    2013-07-01

    Phosphoethanolamine (Pho-s) is a compound involved in phospholipid turnover, acting as a substrate for many phospholipids of the cell membranes. In a recent study, we showed that Pho-s has antitumor effect in the several tumor cells. In this study we evaluated the antitumor activity of synthetic Pho-s on MCF-7 breast cancer cells. Here we demonstrate that Pho-s is cytotoxic to MCF-7 cells in a dose-dependent manner, while it is cytotoxic to MCF10 only at higher concentrations. In addition, Pho-s induces a disruption in mitochondrial membrane potential (Δψm). Furthermore, Pho-s induces mitochondria aggregates in the cytoplasm and DNA fragmentation of MCF-7 cells visualized by confocal microscopy. In agreement with the reduction on Δψm, we showed that Pho-s induces apoptosis followed by an increase in cytochrome c expression and capase-3-like activity in MCF-7 cells. Our results demonstrate that Pho-s induces a cell cycle arrest in the G1 phase through an inhibition of cyclin D1 and stimulates p53. An additional highlight of this study is the finding that Pho-s inhibits Bcl-2, inducing apoptosis through the mitochondrial pathway. Taken together, these results show that Pho-s is a promising compound in the fight against cancer. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  4. INTERACTION OF CLATHRIN WITH LARGE UNILAMELLAR PHOSPHOLIPID-VESICLES AT NEUTRAL PH - LIPID DEPENDENCE AND PROTEIN PENETRATION

    NARCIS (Netherlands)

    SEPPEN, J; RAMALHOSANTOS, J; DECARVALHO, AP; TERBEEST, M; KOK, JW; DELIMA, MCP; HOEKSTRA, D

    1992-01-01

    The interaction of clathrin with large unilamellar vesicles of various lipid compositions has been examined at neutral pH. Clathrin induces leakage of contents of vesicles that contain the acidic phospholipid phosphatidylserine. Leakage is greatly enhanced by the presence of a relatively minor

  5. Co-assembly of chitosan and phospholipids into hybrid hydrogels

    DEFF Research Database (Denmark)

    Mendes, Ana Carina Loureiro; Shekarforoush, Elhamalsadat; Engwer, Christoph

    2016-01-01

    Novel hybrid hydrogels were formed by adding chitosan (Ch) to phospholipids (P) self-assembled particles in lactic acid. The effect of the phospholipid concentration on the hydrogel properties was investigated and was observed to affect the rate of hydrogel formation and viscoelastic properties...

  6. Depletion of acidic phospholipids influences chromosomal replication in Escherichia coli.

    Science.gov (United States)

    Fingland, Nicholas; Flåtten, Ingvild; Downey, Christopher D; Fossum-Raunehaug, Solveig; Skarstad, Kirsten; Crooke, Elliott

    2012-12-01

    In Escherichia coli, coordinated activation and deactivation of DnaA allows for proper timing of the initiation of chromosomal synthesis at the origin of replication (oriC) and assures initiation occurs once per cell cycle. In vitro, acidic phospholipids reactivate DnaA, and in vivo depletion of acidic phospholipids, results in growth arrest. Growth can be restored by the expression of a mutant form of DnaA, DnaA(L366K), or by oriC-independent DNA synthesis, suggesting acidic phospholipids are required for DnaA- and oriC-dependent replication. We observe here that when acidic phospholipids were depleted, replication was inhibited with a concomitant reduction of chromosomal content and cell mass prior to growth arrest. This global shutdown of biosynthetic activity was independent of the stringent response. Restoration of acidic phospholipid synthesis resulted in a resumption of DNA replication prior to restored growth, indicating a possible cell-cycle-specific growth arrest had occurred with the earlier loss of acidic phospholipids. Flow cytometry, thymidine uptake, and quantitative polymerase chain reaction data suggest that a deficiency in acidic phospholipids prolonged the time required to replicate the chromosome. We also observed that regardless of the cellular content of acidic phospholipids, expression of mutant DnaA(L366K) altered the DNA content-to-cell mass ratio.

  7. Influence of the fatty acid composition of high-density lipoprotein phospholipids on the cholesterol efflux from cultured fibroblasts.

    Science.gov (United States)

    Esteva, O; Baudet, M F; Lasserre, M; Jacotot, B

    1986-02-12

    The purpose of this work was to determine whether the changes induced by dietary manipulations in the chemical composition of high-density lipoproteins (HDL) (particularly phospholipid fatty acid composition) modified their capacity to promote [3H]cholesterol efflux from cultured fibroblasts. Plasma HDL were obtained from subjects fed for six successive long periods on diets consisting of one predominant fat: peanut oil, corn oil, olive oil, soybean oil, low erucic acid rapeseed oil or milk fats. The [3H]cholesterol efflux from cells in the presence of plasma HDL was studied by means of normal adult human fibroblasts in culture. The [3H]cholesterol efflux from fibroblasts appeared to be independent of the overall composition of HDL and of the degree of saturation of the HDL phospholipid fatty acids, but it was correlated with the phospholipid fatty acid chain length. The [3H]cholesterol efflux from fibroblasts is highly and positively correlated with the sum of the HDL phospholipid C20, C22, C24 fatty acids, and negatively correlated with the sum of the HDL phospholipid C18 fatty acids.

  8. Role of phospholipids in endocytosis, phagocytosis, and macropinocytosis.

    Science.gov (United States)

    Bohdanowicz, Michal; Grinstein, Sergio

    2013-01-01

    Endocytosis, phagocytosis, and macropinocytosis are fundamental processes that enable cells to sample their environment, eliminate pathogens and apoptotic bodies, and regulate the expression of surface components. While a great deal of effort has been devoted over many years to understanding the proteins involved in these processes, the important contribution of phospholipids has only recently been appreciated. This review is an attempt to collate and analyze the rapidly emerging evidence documenting the role of phospholipids in clathrin-mediated endocytosis, phagocytosis, and macropinocytosis. A primer on phospholipid biosynthesis, catabolism, subcellular distribution, and transport is presented initially, for reference, together with general considerations of the effects of phospholipids on membrane curvature and charge. This is followed by a detailed analysis of the critical functions of phospholipids in the internalization processes and in the maturation of the resulting vesicles and vacuoles as they progress along the endo-lysosomal pathway.

  9. Does Judge Turnover Affect Judicial Performance?

    DEFF Research Database (Denmark)

    Guerra, Alice; Tagliapietra, Claudio

    2017-01-01

    Italy is among the countries with the highest litigation rate and those with the highest duration of trials. This article shows that judge turnover contributes negatively to delays in Italian courts and outlines possible policies for improvement. In Italy, judges can voluntarily move from one...... office to another after three years of mandate, and the law prescribes their transfer after ten years to guarantee their independence. Flaws in the process managing the backlog of outbound judges and the existence of asynchrony between outbound and inbound transfers produce a chain of delays...... to the disposition of court cases. Using a novel dataset on Court of Appeal Districts in Italy (2008–2012), we provide evidence of a strong negative relation between high turnover rates and judicial performance. We find that marginal increases in judge turnover rates lead to a statistically significant decrease...

  10. Nursing home staffing, turnover, and case mix.

    Science.gov (United States)

    Harrington, Charlene; Swan, James H

    2003-09-01

    This study examined the predictors of total nurse and registered nurse (RN) staffing hours per resident day separately in all free-standing California nursing homes (1,555), using staffing data from state cost reports in 1999. This study used a two-stage least squares model, taking into account nursing turnover rates, resident case mix levels, and other factors. As expected, total nurse and RN staffing hours were negatively associated with nurse staff turnover rates and positively associated with resident case mix. Facilities were resource dependent in that a high proportion of Medicare residents predicted higher staffing hours, and a higher proportion of Medicaid residents predicted lower staffing hours and higher turnover rates. Nursing assistant wages were positively associated with total nurse staffing hours. For-profit facilities and high-occupancy rate facilities had lower total nurse and RN staffing hours. Medicaid reimbursement rates and multifacility organizations were positively associated with RN staffing hours.

  11. Analysis of epoxyeicosatrienoic and monohydroxyeicosatetraenoic acids esterified to phospholipids in human red blood cells by electrospray tandem mass spectrometry.

    Science.gov (United States)

    Nakamura, T; Bratton, D L; Murphy, R C

    1997-08-01

    Electrospray ionization (ESI) and tandem mass spectrometry (MS/MS) were used to analyze epoxyeicosatrienoic acids (EETs) and monohydroxyeicosatetraenoic acids (HETEs) isolated from human red blood cell membranes following base hydrolysis. ESI results in the formation of an abundant isobaric carboxylate anion at m/z 319 for both of these oxidized metabolites of arachidonic acid. The product ion spectra from the collision-induced dissociation of this carboxylate anion could be used to identify each of the isomeric eicosanoids from the unique fragment ions of each eicosanoid. The observed product ion spectra were identical with those previously obtained by fast atom bombardment ionization; however, ESI required less EET and HETE for analysis. Both EET and HETE phospholipids were present in human red blood cells (RBCs) and their abundance could be substantially increased by treatment under conditions that would induce free radical oxidation of membrane phospholipids. Following incubation of human RBCs with tert-butyl hydroperoxide (tBuOOH), phospholipids were extracted and purified by normal-phase high-performance liquid chromatography (HPLC) as to glycerophospholipid class containing ethanolamine (GPE), serine (GPS) and choline (GPC) as the polar head group. Each class of phospholipid was hydrolyzed to yield the free carboxylic acid prior to on-line HPLC/ESI-MS/MS analysis. The formation of oxidized arachidonic acid esterified to phospholipids in treated RBCs was found to increase significantly for both esterified EETs in GPE, GPS and GPC which increased 49-, 34- and 59-fold, respectively, and also for esterified HETEs in GPE, GPS and GPC which increased 3-, 4- and 11-fold, respectively, compared with untreated RBCs. These results provide the first characterization of EETs formed non-enzymatically as intact phospholipids in a lipid peroxidation model system.

  12. The impact of phospholipids and phospholipid removal on bioanalytical method performance.

    Science.gov (United States)

    Carmical, Jennifer; Brown, Stacy

    2016-05-01

    Phospholipids (PLs) are a component of cellmembranes, biological fluids and tissues. These compounds are problematic for the bioanalytical chemist, especially when PLs are not the analytes of interest. PL interference with bioanalysis highly impacts reverse-phase chromatographic methods coupled with mass spectrometric detection. Phospholipids are strongly retained on hydrophobic columns, and can cause significant ionization suppression in the mass spectrometer, as they outcompete analyte molecules for ionization. Strategies for improving analyte detection in the presence of PLs are reviewed, including in-analysis modifications and sample preparation strategies. Removal of interfering PLs prior to analysis seems to be most effective atmoderating thematrix effects fromthese endogenous cellular components, and has the potential to simplify chromatography and improve column lifetime. Products targeted at PL removal for sample pre-treatment, as well as products that combine multiplemodes of sample preparation (i.e. Hybrid SPE), show significant promise inmediating the effect on PL interference in bioanalysis.

  13. Allosteric Activation of the Phosphoinositide Phosphatase Sac1 by Anionic Phospholipids

    Science.gov (United States)

    2012-01-01

    Sac family phosphoinositide phosphatases comprise an evolutionarily conserved family of enzymes in eukaryotes. Our recently determined crystal structure of the Sac phosphatase domain of yeast Sac1, the founding member of the Sac family proteins, revealed a unique conformation of the catalytic P-loop and a large positively charged groove at the catalytic site. We now report a unique mechanism for the regulation of its phosphatase activity. Sac1 is an allosteric enzyme that can be activated by its product phosphatidylinositol or anionic phospholipid phosphatidylserine. The activation of Sac1 may involve conformational changes of the catalytic P-loop induced by direct binding with the regulatory anionic phospholipids in the large cationic catalytic groove. These findings highlight the fact that lipid composition of the substrate membrane plays an important role in the control of Sac1 function. PMID:22452743

  14. Dietary DHA supplementation causes selective changes in phospholipids from different brain regions in both wild type mice and the Tg2576 mouse model of Alzheimer's disease.

    Science.gov (United States)

    Bascoul-Colombo, Cécile; Guschina, Irina A; Maskrey, Benjamin H; Good, Mark; O'Donnell, Valerie B; Harwood, John L

    2016-06-01

    Alzheimer's disease (AD) is of major concern in ageing populations and we have used the Tg2576 mouse model to understand connections between brain lipids and amyloid pathology. Because dietary docosahexaenoic acid (DHA) has been identified as beneficial, we compared mice fed with a DHA-supplemented diet to those on a nutritionally-sufficient diet. Major phospholipids from cortex, hippocampus and cerebellum were separated and analysed. Each phosphoglyceride had a characteristic fatty acid composition which was similar in cortex and hippocampus but different in the cerebellum. The biggest changes on DHA-supplementation were within ethanolamine phospholipids which, together with phosphatidylserine, had the highest proportions of DHA. Reciprocal alterations in DHA and arachidonate were found. The main diet-induced alterations were found in ethanolamine phospholipids, (and included their ether derivatives), as were the changes observed due to genotype. Tg mice appeared more sensitive to diet with generally lower DHA percentages when on the standard diet and higher relative proportions of DHA when the diet was supplemented. All four major phosphoglycerides analysed showed age-dependent decreases in polyunsaturated fatty acid contents. These data provide, for the first time, a detailed evaluation of phospholipids in different brain areas previously shown to be relevant to behaviour in the Tg2576 mouse model for AD. The lipid changes observed with genotype are consistent with the subtle alterations found in AD patients, especially for the ethanolamine phospholipid molecular species. They also emphasise the contrasting changes in fatty acid content induced by DHA supplementation within individual phospholipid classes.

  15. Choline Phospholipid Metabolites of Human Vascular Endothelial Cells Altered by Cyclooxygenase Inhibition, Growth Factor Depletion, and Paracrine Factors Secreted by Cancer Cells

    Directory of Open Access Journals (Sweden)

    Noriko Mori

    2003-04-01

    Full Text Available Magnetic resonance studies have previously shown that solid tumors and cancer cells in culture typically exhibit high phosphocholine and total choline. Treatment of cancer cells with the anti-inflammatory agent, indomethacin (INDO, reverted the phenotype of choline phospholipid metabolites in cancer cells towards a less malignant phenotype. Since endothelial cells form a key component of tumor vasculature, in this study, we used MR spectroscopy to characterize the phenotype of choline phospholipid metabolites in human umbilical vein endothelial cells (HUVECs. We determined the effect of growth factors, the anti-inflammatory agent INDO, and conditioned media obtained from a malignant cell line, on choline phospholipid metabolites. Growth factor depletion or treatment with INDO induced similar changes in the choline phospholipid metabolites of HUVECs. Treatment with conditioned medium obtained from MDA-MB-231 cancer cells induced changes similar to the presence of growth factor supplements. These results suggest that cancer cells secrete growth factors and/or other molecules that influence the choline phospholipid metabolism of HUVECs. The ability of INDO to alter choline phospholipid metabolism in the presence of growth factor supplements suggests that the inflammatory response pathways of HUVECs may play a role in cancer cell-HUVEC interaction and in the response of HUVECs to growth factors.

  16. Packing of ganglioside-phospholipid monolayers

    DEFF Research Database (Denmark)

    Majewski, J.; Kuhl, T.L.; Kjær, K.

    2001-01-01

    DPPE monolayer and does not distort the hexagonal in-plane unit cell or out-of-plane two-dimensional (2-D) packing compared with a pure DPPE monolayer. The oligosaccharide headgroups were found to extend normally from the monolayer surface, and the incorporation of these glycolipids into DPPE...... monolayers did not affect hydrocarbon tail packing (fluidization or condensation of the hydrocarbon region). This is in contrast to previous investigations of lipopolymer-lipid mixtures, where the packing structure of phospholipid monolayers was greatly altered by the inclusion of lipids bearing hydrophilic...... polymer groups. Indeed, the lack of packing disruptions by the oligosaccharide groups indicates that protein-GM, interactions, including binding, insertion, chain fluidization, and domain formation (lipid rafts), can be studied in 2-D monolayers using scattering techniques....

  17. Lessons from the "Euro-Phospholipid" project.

    Science.gov (United States)

    Cervera, Ricard

    2008-01-01

    The "Euro-Phospholipid" project started in 1999 with a multicentre, consecutive and prospective design. A total cohort of 1000 patients with antiphospholipid syndrome (APS), derived from 13 countries (Belgium, Bulgaria, Denmark, France, Germany, Greece, Hungary, Israel, Italy, the Netherlands, Portugal, Spain and United Kingdom), has been followed since then by a European consortium that was created as part of the network promoted by the "European Forum on Antiphospholipid Antibodies", a study group devoted to the development of multicentre projects with large populations of APS patients. This project allowed the identification of the prevalence and characteristics of the main clinical and immunological manifestations at the onset and during the evolution of APS and demonstrated that it is possible to recognize more homogeneous subsets of clinical significance.

  18. Food enrichment with marine phospholipid emulsions

    DEFF Research Database (Denmark)

    Lu, Henna Fung Sieng; Nielsen, Nina Skall; Baron, Caroline P.

    Many studies have shown that marine phospholipids (PL) provide more advantages than fish oil. They seem to have better bioavailability, better resistance towards oxidation and higher content of eicosapentaenoic acids and docosahexaenoic acids than fish oil, which essentially contains triglycerides...... marine PL emulsions with and without addition of fish oil. The oxidative stability of marine PL emulsions was significantly influenced by the chemical composition of marine PL used for emulsions preparation. For instance, emulsions with good oxidative stability could be obtained when using raw materials...... with high purity, low fish oil content and high PL, cholesterol and α-tocopherol content. In addition, non-enzymatic browning reactions may also affect the oxidative stability of the marine PL emulsion. These reactions included Strecker degradation and pyrrolization, and their occurrence were due...

  19. Anionic phospholipids modulate peptide insertion into membranes.

    Science.gov (United States)

    Liu, L P; Deber, C M

    1997-05-06

    While the insertion of a hydrophobic peptide or membrane protein segment into the bilayer can be spontaneous and driven mainly by the hydrophobic effect, anionic lipids, which comprise ca. 20% of biological membranes, provide a source of electrostatic attractions for binding of proteins/peptides into membranes. To unravel the interplay of hydrophobicity and electrostatics in the binding of peptides into membranes, we designed peptides de novo which possess the typical sequence Lys-Lys-Ala-Ala-Ala-X-Ala-Ala-Ala-Ala-Ala-X-Ala-Ala-Trp-Ala-Ala-X-Ala-Al a-Ala-Lys-Lys-Lys-Lys-amide, where X residues correspond to "guest" residues which encompass a range of hydrophobicity (Leu, Ile, Gly, and Ser). Circular dichroism spectra demonstrated that peptides were partially (40-90%) random in aqueous buffer but were promoted to form 100% alpha-helical structures by anionic lipid micelles. In neutral lipid micelles, only the relatively hydrophobic peptides (X = L and I) spontaneously adopted the alpha-helical conformation, but when 25% of negatively charged lipids were mixed in to mimic the content of anionic lipids in biomembranes, the less hydrophobic (X = S and G) peptides then formed alpha-helical conformations. Consistent with these findings, fluorescence quenching by the aqueous-phase quencher iodide indicated that in anionic (dimyristoylphosphatidylglycerol) vesicles, the peptide Trp residue was buried in the lipid vesicle hydrophobic core, while in neutral (dimyristoylphosphatidylcholine) vesicles, only hydrophobic (X = L and I) peptides were shielded from the aqueous solution. Trp emission spectra of peptides in the presence of phospholipids doxyl-labeled at the 5-, 7-, 10-, 12-, and 16-fatty acid positions implied not only a transbilayer orientation for inserted peptides but also that mixed peptide populations (transbilayer + surface-associated) may arise. Overall results suggest that for hydrophobic peptides with segmental threshold hydrophobicity below that which

  20. Conformation and Orientation of Phospholipid Molecule in Pure Phospholipid Monolayer During Compressing

    Institute of Scientific and Technical Information of China (English)

    XUE Weilan; WANG Dan; ZENG Zuoxiang; GAO Xuechao

    2013-01-01

    On the basis of energy conservation law and surface pressure isotherm,the conformation energy changes of dipalmitoylphosphatidylcholine(DPPC)and dipalmitoylphosphatidylglycerol(DPPG)in pure phospholipid monolayer at the air/water interface during compression are derived.The optimized conformations of phospholipids at absolute freedom state are simulated by Gaussian 98 software.Based on following assumptions:(1)the conformation energy change is mainly caused by the rotation of one special bond;(2)the atoms of glycerol near the water surface are active;(3)the rotation is motivated by hydrogen-bond action;(4)the rotation of bond is inertial,one simplified track of conformational change is suggested and the conformations of DPPC and DPPG at different states are determined by the plots of conformation energy change vs.dihedral angle.The thickness of the simulated phospholipid monolayer is consistent with published experimental result.According to molecular areas at different states,the molecular orientations in the compressing process are also developed.

  1. Glycoxidized HDL, HDL enriched with oxidized phospholipids and HDL from diabetic patients inhibit platelet function.

    Science.gov (United States)

    Lê, Quang Huy; El Alaoui, Meddy; Véricel, Evelyne; Ségrestin, Bérénice; Soulère, Laurent; Guichardant, Michel; Lagarde, Michel; Moulin, Philippe; Calzada, Catherine

    2015-05-01

    High-density lipoproteins (HDL) possess atheroprotective properties including anti-thrombotic and antioxidant effects. Very few studies relate to the functional effects of oxidized HDL on platelets in type 2 diabetes (T2D). The objective of our study was to investigate the effects of in vitro glycoxidized HDL and HDL from patients with T2D on platelet aggregation and arachidonic acid signaling cascade. At the same time, the contents of hydroxylated fatty acids were assessed in HDL. Compared with control HDL, in vitro glycoxidized HDL had decreased proportions of linoleic (LA) and arachidonic (AA) acids in phospholipids and cholesteryl esters, and increased concentrations of hydroxy-octadecadienoic acids (9-HODE and 13-HODE) and 15-hydroxy-eicosatetraenoic acid (15-HETE), derived from LA and AA respectively, especially hydroxy derivatives esterified in phospholipids. Glycoxidized HDL dose-dependently decreased collagen-induced platelet aggregation by binding to scavenger receptor BI (SR-BI). Glycoxidized HDL prevented collagen-induced increased phosphorylation of platelet p38 MAPK and cytosolic phospholipase A2, as well as intracellular calcium mobilization. HDL enriched with oxidized phosphatidylcholine (PC), namely PC(16:0/13-HODE) dose-dependently inhibited platelet aggregation. Increased concentrations of 9-HODE, 13-HODE, and 15-HETE in phospholipids (2.1-, 2.1-, and 2.4-fold increase, respectively) were found in HDL from patients with T2D, and these HDL also inhibited platelet aggregation via SR-BI. Our results suggest that in vitro glycoxidized HDL as well as HDL from patients with T2D inhibit platelet aggregation, and suggest that oxidized LA-containing phospholipids may contribute to the anti-aggregatory effects of glycoxidized HDL and HDL from patients with T2D.

  2. Comparative evaluation of labelling patterns and turnover of lipids, tagged by 15 (p-/sup 123/I-phenyl-)pentadecanoic and 1-/sup 14/C-palmitic acid

    Energy Technology Data Exchange (ETDEWEB)

    Reske, S.N.; Sauer, W.; Reichmann, K.; Winkler, C. (Bonn Univ. (Germany, F.R.). Inst. fuer Klinische und Experimentelle Nuklearmedizin); Machulla, H.J.; Knust, E.J. (Essen Univ. (Germany, F.R.). Inst. fuer Medizinische Strahlenphysik und Strahlenbiologie)

    1984-06-15

    Uptake and turnover of chloroform/methanol extractable tissue lipids labelled in vivo simultaneously with 15(p-/sup 123/I-phenyl-)pentadecanoic and 1-/sup 14/C-palmitic acid were compared. Lipid turnover studies were performed in fasted pentobarbital-anaesthetized Wistar rats in tissues with highly varying free fatty acid turnover rates. In all tissues investigated, i.e. heart, lung, liver, spleen and kidney, both tracers labelled nearly identical lipid fractions. The main tracer uptake was found in free fatty acids, phospholipids, diglycerides and triglycerides. A highly significant correlation of uptake and turnover in main tissue lipid fractions indicated an essentially identical metabolic pathway of both tracers in intermediary tissue lipid metabolism. Concordant tracer uptake and turnover patterns in tissue of lipids with highly varying fatty acid metabolic rates suggested that intrinsic metabolic activity of the tissue and respective lipid fraction was the major determinant of metabolic handling of both iodophenyl fatty- and palmitic acid. Thus, the feasibility of iodophenylpentadecanoic acid as free fatty acid tracer for studying tissue lipid metabolism is demonstrated. 21 refs.

  3. Employee Development and Turnover Intention: Theory Validation

    Science.gov (United States)

    Rahman, Wali; Nas, Zekeriya

    2013-01-01

    Purpose: This study aims to examine the pattern of behavior of turnover intentions in developing countries "vis-a-vis" the one in advanced countries through the empirical data from public universities in Khyber Pakhtunkhwa, Pakistan. The study provides empirical evidence from academia in Pakistan, thereby enriching the understanding of…

  4. A Turnover Model for the Mexican Maquiladoras.

    Science.gov (United States)

    Maertz, Carl P.; Stevens, Michael J.; Campion, Michael A.

    2003-01-01

    From interviews with 47 Mexican maquiladora workers, a model of voluntary turnover was created and compared with models from the United States, Canada, England, and Australia. Despite similarities, the cultural and economic environment affected the precise content of antecedents in the Mexican model. (Contains 63 references.) (SK)

  5. Costing Child Protective Services Staff Turnover.

    Science.gov (United States)

    Graef, Michelle I.; Hill, Erick L.

    2000-01-01

    Details process of determining a child welfare agency's actual dollar costs directly attributed to protective services staff turnover, using the agency's human resources database and interviews with administrative personnel. Provides formulas and process for calculating specific cost elements due to employee separation, replacement, and training.…

  6. Building Muscles, Keeping Muscles: Protein Turnover During Space Flight

    Science.gov (United States)

    Ferrando, Arny; Bloomberg, Jacob; Lee, Angie (Technical Monitor)

    2002-01-01

    As we age we lose muscle mass and strength. The problem is a matter of use it or lose it and more - a fact to which any active senior can attest. An imbalance in the natural cycle of protein turnover may be a contributing factor to decreased muscle mass. But the answer is not so simple, since aging is associated with changes in hormones, activity levels, nutrition, and often, disease. The human body constantly uses amino acids to build muscle protein, which then breaks down and must be replaced. When protein turnover gets out of balance, so that more protein breaks down than the body can replace, the result is muscle loss. This is not just the bane of aging, however. Severely burned people may have difficulty building new muscle long after the burned skin has been repaired. Answers to why we lose muscle mass and strength - and how doctors can fix it - may come from space. Astronauts usually eat a well-balanced diet and maintain an exercise routine to stay in top health. During long-duration flight, they exercise regularly to reduce the muscle loss that results from being in a near-weightless environment. Despite these precautions, astronauts lose muscle mass and strength during most missions. They quickly recover after returning to Earth - this is a temporary condition in an otherwise healthy population. Members of the STS-107 crew are participating in a study of the effects of space flight, hormone levels, and stress on protein turnover. When we are under stress, the body responds with a change in hormone levels. Researchers hypothesize that this stress-induced change in hormones along with the near-weightlessness might result in the body synthesizing less muscle protein, causing muscles to lose their strength and size. Astronauts, who must perform numerous duties in a confined and unusual environment, experience some stress during their flight, making them excellent candidates for testing the researchers' hypothesis.

  7. Hybrid electrospun chitosan-phospholipids nanofibers for transdermal drug delivery

    DEFF Research Database (Denmark)

    Mendes, Ana Carina Loureiro; Gorzelanny, Christian; Halter, Natalia

    2016-01-01

    Chitosan (Ch) polysaccharide was mixed with phospholipids (P) to generate electrospun hybrid nanofibers intended to be used as platforms for transdermal drug delivery. Ch/P nanofibers exibithed average diameters ranging from 248 +/- 94 nm to 600 +/- 201 nm, depending on the amount of phospholipids...... used. Fourier Transformed Infra-Red (FTIR) spectroscopy and Dynamic Light Scattering (DLS) data suggested the occurrence of electrostatic interactions between amine groups of chitosan with the phospholipid counterparts. The nanofibers were shown to be stable for at least 7 days in Phosphate Buffer...

  8. Nanoporous Silicified Phospholipids and Application to Controlled Glycolic Acid Release

    Directory of Open Access Journals (Sweden)

    Kang SangHwa

    2008-01-01

    Full Text Available Abstract This work demonstrates the synthesis and characterization of novel nanoporous silicified phospholipid bilayers assembled inorganic powders. The materials are obtained by silicification process with silica precursor at the hydrophilic region of phospholipid bilayers. This process involves the co-assembly of a chemically active phospholipids bilayer within the ordered porosity of a silica matrix and holds promise as a novel application for controlled drug release or drug containers with a high level of specificity and throughput. The controlled release application of the synthesized materials was achieved to glycolic acid, and obtained a zero-order release pattern due to the nanoporosity.

  9. Phospholipid remodeling and eicosanoid signaling in colon cancer cells.

    Science.gov (United States)

    Das, Siddhartha; Martinez, Leobarda Robles; Ray, Suparna

    2014-12-01

    Phospholipid remodeling and eicosanoid synthesis are central to lipid-based inflammatory reactions. Studies have revealed that membrane phospholipid remodeling by fatty acids through deacylation/reacylation reactions increases the risk of colorectal cancers (CRC) by allowing the cells to produce excess inflammatory eicosanoids, such as prostaglandins, thromboxanes and leukotrienes. Over the years, efforts have been made to understand the lipid remodeling pathways and to design anti-cancer drugs targeting the enzymes of eicosanoid biosynthesis. Here, we discuss the recent progress in phospholipid remodeling and eicosanoid biosynthesis in CRC.

  10. Staff turnover: occasional friend, frequent foe, and continuing frustration.

    Science.gov (United States)

    McConnell, C R

    1999-09-01

    Turnover appears to be a relatively simple concept. However, considerable confusion results when discussing turnover because of differences in how it is defined--what is counted, how it is counted, and how the rate of turnover is expressed. Turnover is also costly, although not enough attention is paid to turnover's cost because so much of it is indirect and thus not readily visible. There are a variety of causes of turnover, some which can be corrected and some which cannot be avoided. Reducing or otherwise controlling turnover requires continuing management attention to its causes and constant recognition of what can and should be controlled and what cannot be controlled. Ongoing attention to turnover is an essential part of the department manager's role.

  11. Imaging the oxidation effects of the Fenton reaction on phospholipids at the interface between aqueous phase and thermotropic liquid crystals.

    Science.gov (United States)

    Zhang, Minmin; Jang, Chang-Hyun

    2015-08-01

    The lipid peroxidation process has attracted much attention because of the growing evidence of its involvement in the pathogenesis of age-related diseases. Herein, we report a simple, label-free method to study the oxidation of phospholipids by the Fenton reaction at the interface between an aqueous phase and immiscible liquid crystals (LCs). The different images produced by the orientation of 4-cyano-4'-pentylbiphenyl (5CB) corresponded to the presence or absence of oxidized 1,2-dioleoyl-sn-glycero-3-phospho-rac-(1-glycerol) sodium salt (DOPG). The oxidation effects of the Fenton reaction on DOPG were evaluated by monitoring the orientational response of liquid crystals upon contact with the oxidized DOPG solutions. DOPG was oxidized into chain-changed products containing hydroxy, carbonyl, or aldehyde groups, resulting in the rearrangement of the phospholipid layer. This induced the orientational transition of LCs from homeotropic to planar states; therefore, a dark to bright optical shift was observed. This shift was due to the Fenton reaction preventing DOPG to induce the orientational alignment of LCs at the aqueous/LC interface. We also used an ultraviolet spectrophotometer to confirm the effects of oxidation on phospholipids by the Fenton reaction. Using this simple method, a new approach for investigating phospholipid oxidation was established with high resolution and easy accessibility.

  12. Turnover of regulated nurses in long-term care facilities.

    Science.gov (United States)

    Chu, Charlene H; Wodchis, Walter P; McGilton, Katherine S

    2014-07-01

    To describe the relationship between nursing staff turnover in long-term care (LTC) homes and organisational factors consisting of leadership practices and behaviours, supervisory support, burnout, job satisfaction and work environment satisfaction. The turnover of regulated nursing staff [Registered Nurses (RNs) and Registered Practical Nurses (RPNs)] in LTC facilities is a pervasive problem, but there is a scarcity of research examining this issue in Canada. The study was conceptualized using a Stress Process model. Distinct surveys were distributed to administrators to measure organisational factors and to regulated nurses to measure personal and job-related sources of stress and workplace support. In total, 324 surveys were used in the linear regression analysis to examine factors associated with high turnover rates. Higher leadership practice scores were associated with lower nursing turnover; a one score increase in leadership correlated with a 49% decrease in nursing turnover. A significant inverse relationship between leadership turnover and nurse turnover was found: the higher the administrator turnover the lower the nurse turnover rate. Leadership practices and administrator turnover are significant in influencing regulated nurse turnover in LTC. Long-term care facilities may want to focus on building good leadership and communication as an upstream method to minimize nurse turnover. © 2013 John Wiley & Sons Ltd.

  13. 41 CFR 109-27.5002 - Stores inventory turnover ratio.

    Science.gov (United States)

    2010-07-01

    ....5002 Stores inventory turnover ratio. Comparison of investment in stores inventories to annual issues... inventory) or in the average number of month's supply on hand. Turnover or number of month's supply is calculated only on current-use inventory. Performance goals, i.e., a six months investment or a turnover...

  14. Superintendent Turnover in Kentucky. Issues & Answers. REL 2011-No. 113

    Science.gov (United States)

    Johnson, Jerry; Huffman, Tyler; Madden, Karen; Shope, Shane

    2011-01-01

    This study examines superintendent turnover in Kentucky public school districts for 1998/99-2007/08, looking at how turnover varies by rural status, Appalachian and non-Appalachian region, and 2007/08 school district characteristics. Key findings include: (1) Kentucky school districts averaged one superintendent turnover during 1998/99-2007/08;…

  15. Anisotropic metal growth on phospholipid nanodiscs via lipid bilayer expansion

    Science.gov (United States)

    Oertel, Jana; Keller, Adrian; Prinz, Julia; Schreiber, Benjamin; Hübner, René; Kerbusch, Jochen; Bald, Ilko; Fahmy, Karim

    2016-05-01

    Self-assembling biomolecules provide attractive templates for the preparation of metallic nanostructures. However, the intuitive transfer of the “outer shape” of the assembled macromolecules to the final metallic particle depends on the intermolecular forces among the biomolecules which compete with interactions between template molecules and the metal during metallization. The shape of the bio-template may thus be more dynamic than generally assumed. Here, we have studied the metallization of phospholipid nanodiscs which are discoidal particles of ~10 nm diameter containing a lipid bilayer ~5 nm thick. Using negatively charged lipids, electrostatic adsorption of amine-coated Au nanoparticles was achieved and followed by electroless gold deposition. Whereas Au nanoparticle adsorption preserves the shape of the bio-template, metallization proceeds via invasion of Au into the hydrophobic core of the nanodisc. Thereby, the lipidic phase induces a lateral growth that increases the diameter but not the original thickness of the template. Infrared spectroscopy reveals lipid expansion and suggests the existence of internal gaps in the metallized nanodiscs, which is confirmed by surface-enhanced Raman scattering from the encapsulated lipids. Interference of metallic growth with non-covalent interactions can thus become itself a shape-determining factor in the metallization of particularly soft and structurally anisotropic biomaterials.

  16. Looking Beyond Structure: Membrane Phospholipids of Skeletal Muscle Mitochondria.

    Science.gov (United States)

    Heden, Timothy D; Neufer, P Darrell; Funai, Katsuhiko

    2016-08-01

    Skeletal muscle mitochondria are highly dynamic and are capable of tremendous expansion to meet cellular energetic demands. Such proliferation in mitochondrial mass requires a synchronized supply of enzymes and structural phospholipids. While transcriptional regulation of mitochondrial enzymes has been extensively studied, there is limited information on how mitochondrial membrane lipids are generated in skeletal muscle. Herein we describe how each class of phospholipids that constitute mitochondrial membranes are synthesized and/or imported, and summarize genetic evidence indicating that membrane phospholipid composition represents a significant modulator of skeletal muscle mitochondrial respiratory function. We also discuss how skeletal muscle mitochondrial phospholipids may mediate the effect of diet and exercise on oxidative metabolism. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Structure and mechanism of ATP-dependent phospholipid transporters

    DEFF Research Database (Denmark)

    Lopez Marques, Rosa Laura; Poulsen, Lisbeth Rosager; Bailly, Aurélien

    2015-01-01

    Background ATP-binding cassette (ABC) transporters and P4-ATPases are two large and seemingly unrelated families of primary active pumps involved in moving phospholipids from one leaflet of a biological membrane to the other. Scope of review This review aims to identify common mechanistic features...... in the way phospholipid flipping is carried out by two evolutionarily unrelated families of transporters. Major conclusions Both protein families hydrolyze ATP, although they employ different mechanisms to use it, and have a comparable size with twelve transmembrane segments in the functional unit. Further......, despite differences in overall architecture, both appear to operate by an alternating access mechanism and during transport they might allow access of phospholipids to the internal part of the transmembrane domain. The latter feature is obvious for ABC transporters, but phospholipids and other hydrophobic...

  18. The enteric bacterial metabolite propionic acid alters brain and plasma phospholipid molecular species: further development of a rodent model of autism spectrum disorders

    Directory of Open Access Journals (Sweden)

    Thomas Raymond H

    2012-07-01

    Full Text Available Abstract Gastrointestinal symptoms and altered blood phospholipid profiles have been reported in patients with autism spectrum disorders (ASD. Most of the phospholipid analyses have been conducted on the fatty acid composition of isolated phospholipid classes following hydrolysis. A paucity of information exists on how the intact phospholipid molecular species are altered in ASD. We applied ESI/MS to determine how brain and blood intact phospholipid species were altered during the induction of ASD-like behaviors in rats following intraventricular infusions with the enteric bacterial metabolite propionic acid. Animals were infused daily for 8 days, locomotor activity assessed, and animals killed during the induced behaviors. Propionic acid infusions increased locomotor activity. Lipid analysis revealed treatment altered 21 brain and 30 blood phospholipid molecular species. Notable alterations were observed in the composition of brain SM, diacyl mono and polyunsaturated PC, PI, PS, PE, and plasmalogen PC and PE molecular species. These alterations suggest that the propionic acid rat model is a useful tool to study aberrations in lipid metabolism known to affect membrane fluidity, peroxisomal function, gap junction coupling capacity, signaling, and neuroinflammation, all of which may be associated with the pathogenesis of ASD.

  19. Kappa opioid receptors stimulate phosphoinositide turnover in rat brain

    Energy Technology Data Exchange (ETDEWEB)

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

    1990-01-01

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

  20. Regional distribution of phospholipids in porcine vitreous humor.

    Science.gov (United States)

    Schnepf, Abigail; Yappert, Marta Cecilia; Borchman, Douglas

    2017-07-01

    This project explores the regional phospholipid distribution in porcine vitreous humor, retina, and lens. Matrix-assisted laser desorption mass spectrometry has been used previously to image lipids, proteins, and other metabolites in retinas and lenses. However, the regional composition of phospholipids in vitreous humors is not known. To address this issue, we have applied this mass spectral method to explore the regional phospholipid distribution in porcine vitreous humor both ex-situ and in-vitro. To establish the possible source(s) of phospholipids in the vitreous humor, compositional studies of the lens and retina were also pursued. Due to the overall low levels of phospholipids in vitreous humor, it was necessary to optimize the experimental approaches for ex-situ and in-vitro studies. The sensitivity observed in the spectra of methanol extracts from the lens and retina was higher than that for methanol:chloroform extracts, but the compositional trends were the same. A fourfold improvement in sensitivity was observed in the analysis of vitreous humor extracts obtained with the Bligh and Dyer protocol relative to the other two extraction methods. For ex-situ studies, the 'stamp method' with para-nitroaniline as the matrix was chosen. Throughout the vitreous humor, phosphatidylcholines were the most abundant phospholipids. In-vitro results showed higher relative levels of phospholipids compared to the 'stamp' method. However, more details in the regional phospholipid distribution were provided by the ex-situ approach. Both in-vitro and ex-situ results indicated higher levels of phospholipids in the posterior vitreous region, followed by the anterior and central regions. The posterior region contained more unsaturated species whereas more saturated phospholipids were detected in the anterior region. The observed trends suggest that the phospholipids detected in the posterior vitreous humor migrate from the retina and associated vasculature while those present in

  1. Rhizosphere bacterial carbon turnover is higher in nucleic acids than membrane lipids: implications for understanding soil carbon cycling

    Directory of Open Access Journals (Sweden)

    Ashish A. Malik

    2015-04-01

    Full Text Available Using a pulse-chase 13CO2 plant labeling experiment we compared the flow of plant carbon into macromolecular fractions of root-associated soil microorganisms. Time dependent 13C dilution patterns in microbial cellular fractions were used to calculate their turnover time. The turnover times of microbial biomolecules were found to vary: microbial RNA (19 h and DNA (30 h turned over fastest followed by chloroform fumigation extraction-derived soluble cell lysis products (14 d, while phospholipid fatty acids (PLFAs had the slowest turnover (42 d. PLFA/NLFA 13C analyses suggest that both mutualistic arbuscular mycorrhizal and saprophytic fungi are dominant in initial plant carbon uptake. In contrast, high initial 13C enrichment in RNA hints at bacterial importance in initial C uptake due to the dominance of bacterial derived RNA in total extracts of soil RNA. To explain this discrepancy, we observed low renewal rate of bacterial lipids, which may therefore bias lipid fatty acid based interpretations of the role of bacteria in soil microbial food webs. Based on our findings, we question current assumptions regarding plant-microbe carbon flux and suggest that the rhizosphere bacterial contribution to plant assimilate uptake could be higher. This highlights the need for more detailed quantitative investigations with nucleic acid biomarkers to further validate these findings.

  2. Phospholipid synthesis rates in the eastern subtropical South Pacific Ocean

    Directory of Open Access Journals (Sweden)

    B. A. S. Van Mooy

    2008-02-01

    Full Text Available Membrane lipid molecules are a major component of planktonic organisms and this is particularly true of the microbial picoplankton that dominate the open ocean; with their high surface-area to volume ratios, the synthesis of membrane lipids places a major demand on their overall cell metabolism. Specifically, the synthesis of cell membrane phospholipids creates a demand for the nutrient phosphorus, and we sought to refine our understanding of the role of phospholipids in the upper ocean phosphorus cycle. We measured the rates of phospholipid synthesis in a transect of the eastern subtropical South Pacific from Easter Island to Concepcion, Chile as part of the BIOSOPE program. Our approach combined standard phosphorus radiotracer incubations and lipid extraction methods. We found that phospholipid synthesis rates varied from less than 1 to greater than 200 pmol P L−1 h−1, and that phospholipid synthesis contributed between less than 5% to greater than 22% of the total PO43− incorporation rate. Changes in the percentage that phospholipid synthesis contributed to total PO43− uptake were strongly correlated with the ratio of primary production to bacterial production, which supported our hypothesis that heterotrophic bacteria were the primary agents of phospholipid synthesis. The spatial variation in phospholipid synthesis rates underscored the importance of heterotrophic bacteria in the phosphorus cycle of the eastern subtropical South Pacific, particularly the hyperoligotrophic South Pacific subtropical gyre.

  3. Organizational-level study of the impact of past turnover on future turnover in the Sultanate of Oman

    Directory of Open Access Journals (Sweden)

    Ruqaiya Mohamed Al Balushi

    2013-10-01

    Full Text Available Turnover phenomena attracted researchers from all over the world for generations. Most of this research was directed towards turnover antecedents with a few scattered conceptual and empirical studies related to turnover consequences. The purpose of this study is to investigate the impact of past turnover on future turnover in public organizations, in addition to test the mediation role of organizational climate in this relationship. Public schools as separate identities were the best choice as the study sample. Data were collected through questionnaires from 142 public schools in all educational regions in Oman. Two-step structural equation modeling approach, and nested model comparison were used for data analysis. The results revealed that: (1 past turnover predicts future turnover, significantly; (2 organizational climate fails to mediate this relationship. The study added to the body of knowledge by confirming Staw’s hypothesis relating past turnover to future turnover in the Omani context. Human resource professionals and educational administration practitioners may play an important role in decreasing future turnover by tackling and decreasing past turnover, in addition to improving the relationship climate in schools. The study is limited to public schools in Oman and further studies about turnover consequences in the Arabic context are needed to affirm the results.

  4. Molecular Insights into Phospholipid -- NSAID Interactions

    Science.gov (United States)

    Babu Boggara, Mohan; Krishnamoorti, Ramanan

    2007-03-01

    Non steroidal anti inflammatory drugs (NSAIDs) e.g. Aspirin and Ibuprofen, with chronic usage cause gastro intestinal (GI) toxicity. It has been shown experimentally that NSAIDs pre-associated with phospholipids reduce the GI toxicity and also increase the therapeutic activity of these drugs compared to the unmodified ones. Using all atomistic simulations and two different methodologies, we studied the partitioning behavior of two model NSAIDs (Aspirin and Ibuprofen) as a function of pH and drug loading. The results from two methodologies are consistent in describing the equilibrium drug distribution in the bilayers. Additionally, the heterogeneity in density and polarity of the bilayer in the normal direction along with the fact that NSAIDs are amphiphilic (all of them have a carboxylic acid group and a non-polar part consisting of aromatic moieties), indicate that the diffusion mechanism in the bilayer is far different compared to the same in a bulk medium. This study summarizes the various effects of NSAIDs and their behavior inside the lipid bilayer both as a function of pH and drug concentration.

  5. Enhancement by cytidine of membrane phospholipid synthesis

    Science.gov (United States)

    G-Coviella, I. L.; Wurtman, R. J.

    1992-01-01

    Cytidine, as cytidine 5'-diphosphate choline, is a major precursor in the synthesis of phosphatidylcholine in cell membranes. In the present study, we examined the relationships between extracellular levels of cytidine, the conversion of [14C]choline to [14C]phosphatidylcholine, and the net syntheses of phosphatidylcholine and phosphatidylethanolamine by PC12 cells. The rate at which cytidine (as [3H]cytidine) was incorporated into the PC12 cells followed normal Michaelis-Menten kinetics (Km = 5 microM; Vmax = 12 x 10(-3) mmol/mg of protein/min) when the cytidine concentrations in the medium were below 50 microM; at higher concentrations, intracellular [3H]cytidine nucleotide levels increased linearly. Once inside the cell, cytidine was converted mainly into cytidine triphosphate. In pulse-chase experiments, addition of cytidine to the medium caused a time- and dose-dependent increase (by up to 30%) in the incorporation of [14C]choline into membrane [14C]-phosphatidylcholine. When the PC12 cells were supplemented with both cytidine and choline for 14 h, small but significant elevations (p less than 0.05) were observed in their absolute contents of membrane phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine, all increasing by 10-15% relative to their levels in cells incubated with choline alone. Exogenous cytidine, acting via cytidine triphosphate, can thus affect the synthesis and levels of cell membrane phospholipids.

  6. Biomimetic surface modification of polyurethane with phospholipids grafted carbon nanotubes.

    Science.gov (United States)

    Tan, Dongsheng; Liu, Liuxu; Li, Zhen; Fu, Qiang

    2015-08-01

    To improve blood compatibility of polyurethane (PU), phospholipids grafted carbon nanotubes (CNTs) were prepared through zwitterion-mediated cycloaddition reaction and amide condensation, and then were added to the PU as fillers via solution mixing to form biomimetic surface. The properties of phospholipids grafted CNTs (CNT-PC) were investigated by thermal gravimetric analysis (TGA), X-ray photoelectron spectroscopy (XPS) and proton nuclear magnetic resonance ((1) H NMR). The results indicated that the phospholipids were grafted onto CNTs in high efficiency, and the hydrophilicity and dispersibility of the modified CNTs were improved effectively. The structures and properties of composites containing CNT-PC were investigated by optical microscope, XPS, and water contact angles. The results indicated that phospholipids were enriched on the surface with addition of 0.1 wt % of CNT-PC, which significantly reduced protein adsorption and platelet adhesion. The method of carrying phospholipids on the nanofiller to modify polymers has provided a promising way of constructing biomimetic phospholipid membrane on the surface to improve blood compatibility.

  7. Phospholipid Synthesis in Sindbis Virus-Infected Cells

    Science.gov (United States)

    Waite, Marilynn R. F.; Pfefferkorn, E. R.

    1970-01-01

    We investigated the metabolic requirements for the decrease in phospholipid synthesis previously observed by Pfefferkorn and Hunter in primary cultures of chick embryo fibroblasts infected with Sindbis virus. The incorporation of 32PO4 into all classes of phospholipids was found to decline at the same rate and to the same extent; thus, incorporation of 14C-choline into acid-precipitable form provided a convenient measure of phospholipid synthesis that was used in subsequent experiments. Experiments with temperature-sensitive mutants suggested that some viral ribonucleic acid (RNA) synthesis was essential for the inhibition of choline incorporation, but that functional viral structural proteins were not required. The reduction in phospholipid synthesis was probably a secondary effect of infection resulting from viral inhibition of the cellular RNA and protein synthesis. All three inhibitory effects required about the same amount of viral RNA synthesis; the inhibition of host RNA and protein synthesis began sooner than the decline in phospholipid synthesis; and both actinomycin D and cycloheximide inhibited 14C-choline incorporation in uninfected cells. In contrast, incorporation of 14C-choline into BHK-21 cells was not decreased by 10 hr of exposure to actinomycin D and declined only slowly after cycloheximide treatment. Growth of Sindbis virus in BHK cells did not cause the marked stimulation of phospholipid synthesis seen in picornavirus infections of other mammalian cells; however, inhibition was seen only late in infection. PMID:5530011

  8. Regulation of phospholipid synthesis in Saccharomyces cerevisiae by zinc.

    Science.gov (United States)

    Iwanyshyn, Wendy M; Han, Gil-Soo; Carman, George M

    2004-05-21

    Zinc is an essential nutrient required for the growth and metabolism of eukaryotic cells. In this work, we examined the effects of zinc depletion on the regulation of phospholipid synthesis in the yeast Saccharomyces cerevisiae. Zinc depletion resulted in a decrease in the activity levels of the CDP-diacylglycerol pathway enzymes phosphatidylserine synthase, phosphatidylserine decarboxylase, phosphatidylethanolamine methyltransferase, and phospholipid methyltransferase. In contrast, the activity of phosphatidylinositol synthase was elevated in response to zinc depletion. The level of Aut7p, a marker for the induction of autophagy, was also elevated in zinc-depleted cells. For the CHO1-encoded phosphatidylserine synthase, the reduction in activity in response to zinc depletion was controlled at the level of transcription. This regulation was mediated through the UAS(INO) element and by the transcription factors Ino2p, Ino4p, and Opi1p that are responsible for the inositol-mediated regulation of UAS(INO)-containing genes involved in phospholipid synthesis. Analysis of the cellular composition of the major membrane phospholipids showed that zinc depletion resulted in a 66% decrease in phosphatidylethanolamine and a 29% increase in phosphatidylinositol. A zrt1Delta zrt2Delta mutant (defective in the plasma membrane zinc transporters Zrt1p and Zrt2p) grown in the presence of zinc exhibited a phospholipid composition similar to that of wild type cells depleted for zinc. These results indicated that a decrease in the cytoplasmic levels of zinc was responsible for the alterations in phospholipid composition.

  9. Occupational turnover intentions among substance abuse counselors.

    Science.gov (United States)

    Rothrauff, Tanja C; Abraham, Amanda J; Bride, Brian E; Roman, Paul M

    2011-01-01

    This study examined predictor, moderator, and mediator variables of occupational turnover intention (OcTI) among substance abuse counselors. Data were obtained via questionnaires from 929 counselors working in 225 private substance abuse treatment (SAT) programs across the United States. Hierarchical multiple regression models were conducted to assess predictor, moderator, and mediator variables of OcTI. OcTI scores were relatively low on a 7-point scale, indicating that very few counselors definitely intended to leave the SAT field. Age, certification, positive perceptions of procedural and distributive justice, and hospital-based status negatively predicted OcTI. Counselors' substance use disorder-impacted history moderated the association between organizational commitment and OcTI. Organizational turnover intention partially mediated the link between organizational commitment and OcTI. Workforce stability might be achieved by promoting perceptions of advantages to working in a particular treatment program, having organizational commitment, showing appreciation for counselors' work, and valuing employees from diverse backgrounds.

  10. Review of nursing turnover research, 1977-1996.

    Science.gov (United States)

    Tai, T W; Bame, S I; Robinson, C D

    1998-12-01

    Turnover represents a major problem for health care services in terms of cost and quality of care given. As a result, turnover has been the subject of a large number of investigations. However, the variety of study populations, research methodologies, and inconsistent definitions and measurements of turnover lead to difficulties when attempting to compare studies. The purpose of this paper is to present: (1) a summary of turnover study methods and procedures, and (2) a summary of socio-demographic, organizational, and social support factors associated with turnover of nursing staff.

  11. Measuring temporal turnover in ecological communities

    OpenAIRE

    Shimadzu, Hideyasu; Dornelas, Maria; Magurran, Anne

    2015-01-01

    The authors acknowledge support from the European Research Council (project BioTIME 250189) and the Royal Society. MD acknowledges funding from the Marine Alliance for Science and Technology Scotland (MASTS). MASTS is funded by the Scottish Funding Council (grant reference HR09011) and contributing institutions. 1.Range migrations in response to climate change, invasive species and the emergence of novel ecosystems highlight the importance of temporal turnover in community composition as a...

  12. High bone turnover in Irish professional jockeys.

    LENUS (Irish Health Repository)

    Waldron-Lynch, F

    2012-02-01

    SUMMARY: Professional jockeys are routinely exposed to high impact trauma and sustain fractures frequently. We found that jockeys restrict their caloric intake in order to maintain regulation weights, and that bone turnover is high. There are significant health and safety implications for the racing industry. INTRODUCTION: Professional jockeys routinely sustain fractures from high impact falls. Jockeys maintain a low percentage body fat and a low body mass index (BMI) to achieve low weight targets in order to race. We evaluated dietary habits and bone metabolism in jockeys. METHODS: Bone mineral density (BMD) was measured in 27 male jockeys of the 144 jockeys licensed in Ireland. Fourteen (52%) had BMD T score below -1.0, of whom 12 consented to clinical review, nutritional survey, endocrine studies, and bone turnover markers (BTM). BTM were compared to age- and sex-matched controls (n = 16). RESULTS: BMI was 20.6 +\\/- 1.7 kg\\/m(2); previous fracture frequency was 3.2 +\\/- 2.0 per rider. All had normal endocrine axes. The jockeys\\' diet as determined by a 7-day dietary recall was deficient in energy, calcium, and vitamin D intake. Compared with the control group, the jockey group had evidence of increased bone turnover. CONCLUSIONS: A substantial proportion of the professional jockeys in Ireland have low-normal BMD, low BMI, and high bone turnover that may result from weight and dietary restrictions. These factors seem to have a deleterious effect on their bone health and predispose the jockeys to a high fracture risk that should be remediated.

  13. Stock Option Compensation and Managerial Turnover

    OpenAIRE

    Raluca Georgiana NASTASESCU

    2009-01-01

    This study examines the association between managerial turnover and equity-based compensation. I investigate whether stock options act to bond executives to their firms and whether retention of managers is a motivation of companies in designing CEO incentive contracts. The results show that stock options do negatively influence the probability of a CEO leaving the company. The monetary cost of losing the value of equity-based compensation package keeps the manager with his company. I also fin...

  14. Quantitative analysis of protein turnover in plants.

    Science.gov (United States)

    Nelson, Clark J; Li, Lei; Millar, A Harvey

    2014-03-01

    Proteins are constantly being synthesised and degraded as plant cells age and as plants grow, develop and adapt the proteome. Given that plants develop through a series of events from germination to fruiting and even undertake whole organ senescence, an understanding of protein turnover as a fundamental part of this process in plants is essential. Both synthesis and degradation processes are spatially separated in a cell across its compartmented structure. The majority of protein synthesis occurs in the cytosol, while synthesis of specific components occurs inside plastids and mitochondria. Degradation of proteins occurs in both the cytosol, through the action of the plant proteasome, and in organelles and lytic structures through different protease classes. Tracking the specific synthesis and degradation rate of individual proteins can be undertaken using stable isotope feeding and the ability of peptide MS to track labelled peptide fractions over time. Mathematical modelling can be used to follow the isotope signature of newly synthesised protein as it accumulates and natural abundance proteins as they are lost through degradation. Different technical and biological constraints govern the potential for the use of (13)C, (15)N, (2)H and (18)O for these experiments in complete labelling and partial labelling strategies. Future development of quantitative protein turnover analysis will involve analysis of protein populations in complexes and subcellular compartments, assessing the effect of PTMs and integrating turnover studies into wider system biology study of plants.

  15. PERAN STRES KERJA DAN KEPUASAN KERJA UNTUK MENGURANGI TURNOVER INTENTION

    Directory of Open Access Journals (Sweden)

    Syarifah Nazenin

    2014-09-01

    Full Text Available Tujuan penelitian ini untuk menguji pengaruh variabel stres kerja dan kepuasan kerja pada turnover intention karyawan tetap bagian produksi. Sampel penelitian ini adalah 86 responden, menggunakan metode Slovin dengan teknik probability sampling dengan jenis proportionate random sampling. Berdasarkan hasil penelitian, menunjukkan bahwa stres kerja berpengaruh positif signifikan pada turnover intention. Kemudian, kepuasan kerja berpengaruh negatif signifikan. Penelitian ini menyimpulkan, bahwa stres kerja berpengaruh positif dan signifikan pada turnover intention karyawan dan kepuasan kerja berpengaruh negatif dan signifikan terhadap turnover intention karyawan. Implikasi manajerial yang bisa dilakukan adalah dengan pengurangan tingkat stres karyawan dan membuat program untuk tujuan menekan turnover intention, seperti kesempatan promosi dan meningkatkan reward karyawan. The purpose of this study conducted to examine the effect of work stress and job satisfaction on turnover intention of employee in production department. The sample was 86 respondent, using Slovin method with proportionate random sampling technique. The result showed that job stress has a positive effect on turnover intention while job satisfaction has a negative effect on turnover intention. This study conclude that job stress has positive and significant impact on employee turnover intention and job satisfaction significantly and negatively related to turnover intention of employees. Therefore, it is recommended to managerial level people to reduce stress levels in employees and to create a program for pressing turnover intention, such as promotional opportunities and improve employee rewards.

  16. PERAN STRES KERJA DAN KEPUASAN KERJA UNTUK MENGURANGI TURNOVER INTENTION

    Directory of Open Access Journals (Sweden)

    Syarifah Nazenin

    2014-09-01

    Full Text Available Tujuan penelitian ini untuk menguji pengaruh variabel stres kerja dan kepuasan kerja pada turnover intention karyawan tetap bagian produksi. Sampel penelitian ini adalah 86 responden, menggunakan metode Slovin dengan teknik probability sampling dengan jenis proportionate random sampling. Berdasarkan hasil penelitian, menunjukkan bahwa stres kerja berpengaruh positif signifikan pada turnover intention. Kemudian, kepuasan kerja berpengaruh negatif signifikan. Penelitian ini menyimpulkan, bahwa stres kerja berpengaruh positif dan signifikan pada turnover intention karyawan dan kepuasan kerja berpengaruh negatif dan signifikan terhadap turnover intention karyawan. Implikasi manajerial yang bisa dilakukan adalah dengan pengurangan tingkat stres karyawan dan membuat program untuk tujuan menekan turnover intention, seperti kesempatan promosi dan meningkatkan reward karyawan. The purpose of this study conducted to examine the effect of work stress and job satisfaction on turnover intention of employee in production department. The sample was 86 respondent, using Slovin method with proportionate random sampling technique. The result showed that job stress has a positive effect on turnover intention while job satisfaction has a negative effect on turnover intention. This study conclude that job stress has positive and significant impact on employee turnover intention and job satisfaction significantly and negatively related to turnover intention of employees. Therefore, it is recommended to managerial level people to reduce stress levels in employees and to create a program for pressing turnover intention, such as promotional opportunities and improve employee rewards.

  17. Turnover rate of blood glucose in diabetic KK mice.

    Science.gov (United States)

    Fujimoto, K; Sakaguchi, T; Ui, M

    1981-07-01

    Metabolic rate constants for blood glucose turnover were estimated based on the decay of [U-14C, 6-3H]glucose injected intravenously in genetically diabetic KK mice. Comparison was made with the rate constants similarly obtained with non-diabetic and streptozotocin-induced diabetic ICR mice. Recycling of blood glucose via the Cori cycle, as estimated from the difference in the decay rate between 14C and 3H, was more active in KK mice than in non-diabetic and diabetic ICR mice. The Cori cycle activity was reduced by beta-adrenergic blockade in KK mice and was enhanced by alpha-blockade in ICR mice. It is concluded that predominance of beta-adrenergic functions in KK mice is responsible for activation of the Cori cycle as one of the mechanisms for metabolic resistance to endogenous insulin.

  18. Treatment staff turnover in organizations implementing evidence-based practices: turnover rates and their association with client outcomes.

    Science.gov (United States)

    Garner, Bryan R; Hunter, Brooke D; Modisette, Kathryn C; Ihnes, Pamela C; Godley, Susan H

    2012-03-01

    High staff turnover has been described as a problem for the substance use disorder treatment field. This assertion is based primarily on the assumption that staff turnover adversely impacts treatment delivery and effectiveness. This assumption, however, has not been empirically tested. In this study, we computed annualized rates of turnover for treatment staff (N = 249) participating in an evidence-based practice implementation initiative and examined the association between organizational-level rates of staff turnover and client-level outcomes. Annualized rates of staff turnover were 31% for clinicians and 19% for clinical supervisors. In addition, multilevel analyses did not reveal the expected relationship between staff turnover and poorer client-level outcomes. Rather, organizational-level rates of staff turnover were found to have a significant positive association with two measures of treatment effectiveness: less involvement in illegal activity and lower social risk. Possible explanations for these findings are discussed. Copyright © 2012 Elsevier Inc. All rights reserved.

  19. Fish Oil Supplementation in Humans: Effects on Platelet Responses, Phospholipid Composition and Metabolism.

    Science.gov (United States)

    Skeaff, Clark Murray

    Platelets are believed to play a significant role in the development of occlusive vascular diseases. Epidemiological reports have correlated the high intake of marine foods, rich in omega3 fatty acids, with diminished platelet responses and a low incidence of arterial thrombosis and myocardial infarction. The activation of platelet responses is mediated by the accelerated metabolism of membrane phospholipid; therefore, it was of interest to examine, in human volunteers, the effect of a dietary fish oil concentrate (MaxEPA), enriched in omega 3 polyunsaturated fatty acids, on platelet aggregation and phospholipid composition/metabolism. For the complete separation of cellular phospholipids, a one-dimensional thin-layer chromatography system using silica-gel pre-coated glass plates was developed. The solvent system consisted of CHCl_3/CH_3OH/CH _3COOH/H_2O (50/37.5/3.5/2.0, by vol), required approximately 90-120 minutes for full phospholipid separation, and was highly reproducible even under conditions of variable humidity and temperature. The consumption of a fish oil concentrate (MaxEPA) for 6 weeks (3.6 g of 20:5omega 3 and 2.4 g of 22:6omega3 per day) diminished both the collagen- and platelet activating factor-induced maximum aggregation responses in washed human platelet suspensions by 50.1% and 27.2%, respectively, as compared to initial unsupplemented baseline responses. Thrombin -induced aggregation remained unchanged. Thrombin stimulation of intact human platelets produced a significant decrease in the mass of phosphatidylinositol in plasma membrane. In platelets pre-labelled with (2-^3H) glycerol and stimulated with either thrombin or low-dose collagen, the loss of (^3H) phosphatidylinositol did not differ between those subjects consuming olive oil or fish oil. Likewise, the thrombin-stimulated accumulation of diacylglycerol, an activator of protein kinase C, was unaffected by fish oil consumption. The ratio of collagen -induced increase in radioactivity

  20. Structural Insights into the Phospholipid Binding Specificity of Human Evectin-2

    Science.gov (United States)

    Okazaki, Seiji; Kato, Ryuichi; Wakatsuki, Soichi; Uchida, Yasunori; Taguchi, Tomohiko; Arai, Hiroyuki

    Evectin-2 is a recycling endosomal protein and plays an essential role in retrograde transport from recycling endosomes to the trans-Golgi network. The pleckstrin homology (PH) domain of Evectin-2 can specifically binds to phosphatidylserine (PS), which is enriched in recycling endosomes. To elucidate the molecular mechanism how it specifically binds to PS, we solved the crystal structures of human Evectin-2 PH domain for apo and O-phospho-L-serine complexed forms at 1.75 and 1.00 Å resolution, respectively. These structural analyses clearly show that PS-induced conformational change of Evectin-2 PH domain effectively explains the strict phospholipid binding specificity.

  1. Turnover in health care: the mediating effects of employee engagement.

    Science.gov (United States)

    Collini, Stevie A; Guidroz, Ashley M; Perez, Lisa M

    2015-03-01

    This study aimed to understand the interaction between interpersonal respect, diversity climate, mission fulfilment and engagement to better predict turnover in health care. Registered nurse turnover has averaged 14% and current nursing shortages are expected to spread. Few studies have studied employee engagement as a mediator between organisational context and turnover. Study participants were employees working within 185 departments across ten hospitals within a large healthcare organisation in the USA. Although a total of 5443 employees work in these departments, employee opinion survey responses were aggregated by department before being linked to turnover rates gathered from company records. Engagement fully mediated the relationship between respect and turnover and the relationship between mission fulfilment and turnover. Diversity climate was not related to turnover. Turnover in health care poses a significant threat to the mission of creating a healing environment for patients and these results demonstrate that workplace respect and connection to the mission affect turnover by decreasing engagement. The findings demonstrated that to increase engagement, and improve turnover rates in health care, it would be beneficial for organisations, and nurse management to focus on improving mission fulfilment and interpersonal relationships. © 2013 John Wiley & Sons Ltd.

  2. Perforin rapidly induces plasma membrane phospholipid flip-flop.

    Directory of Open Access Journals (Sweden)

    Sunil S Metkar

    Full Text Available The cytotoxic cell granule secretory pathway is essential for host defense. This pathway is fundamentally a form of intracellular protein delivery where granule proteases (granzymes from cytotoxic lymphocytes are thought to diffuse through barrel stave pores generated in the plasma membrane of the target cell by the pore forming protein perforin (PFN and mediate apoptotic as well as additional biological effects. While recent electron microscopy and structural analyses indicate that recombinant PFN oligomerizes to form pores containing 20 monomers (20 nm when applied to liposomal membranes, these pores are not observed by propidium iodide uptake in target cells. Instead, concentrations of human PFN that encourage granzyme-mediated apoptosis are associated with pore structures that unexpectedly favor phosphatidylserine flip-flop measured by Annexin-V and Lactadherin. Efforts that reduce PFN mediated Ca influx in targets did not reduce Annexin-V reactivity. Antigen specific mouse CD8 cells initiate a similar rapid flip-flop in target cells. A lipid that augments plasma membrane curvature as well as cholesterol depletion in target cells enhance flip-flop. Annexin-V staining highly correlated with apoptosis after Granzyme B (GzmB treatment. We propose the structures that PFN oligomers form in the membrane bilayer may include arcs previously observed by electron microscopy and that these unusual structures represent an incomplete mixture of plasma membrane lipid and PFN oligomers that may act as a flexible gateway for GzmB to translocate across the bilayer to the cytosolic leaflet of target cells.

  3. Magainin 2a - Induced Permeabilization of Phospholipid Vesicles

    Science.gov (United States)

    1991-01-02

    Dr. Hao- Chia Chen Dr. Robert W. Williams Dr. Noreen Williams for his guidance, advice, positive approach to research, and detailed review of...study the interaction of magainin peptides with membranes. An assay which measures the release of the fluores - cent dye, 6CF from 6CF-loaded SUVs

  4. Phospholipid dynamics in graphene of different topologies: predictive modeling

    Science.gov (United States)

    Glukhova, O. E.; Slepchenkov, M. M.

    2017-02-01

    The subject of our scientific interest is the dynamics of the phospholipid molecules into a corrugated graphene sheet. According to our assumption by changing the topology of graphene properly it is possible to find the ways for management of the selective localization of phospholipid molecules to form the desired configuration of these structures. We considered DPPC (dipalmitoylphosphatidylcholine) phospholipids, which are the part of cell membranes and lipoproteins. We investigated the behavior of the phospholipids on the graphene sheet consisting of 1710 atoms with the size of 6.9 nm along the zigzag edge and 6.25 nm along the armchair edge. The numerical experiment was carried out using the original AMBER/AIREBO hybrid method with Lennard-Jones potential to describe the interaction between unbound atoms of different structures. The temperature was maintained at 300 K during the numerical experiment. All numerical experiments were performed using KVAZAR software system. We considered several cases of corrugated graphene with different width and dept of the corrugation. Special attention in our work was paid to the orientation of the phospholipids in the plane of graphene sheet.

  5. Erythrocyte phospholipid and polyunsaturated fatty acid composition in diabetic retinopathy.

    Directory of Open Access Journals (Sweden)

    Philippe Koehrer

    Full Text Available Long chain polyunsaturated fatty acids (LCPUFAs including docosahexaenoic acid and arachidonic acid are suspected to play a key role in the pathogenesis of diabetes. LCPUFAs are known to be preferentially concentrated in specific phospholipids termed as plasmalogens. This study was aimed to highlight potential changes in the metabolism of phospholipids, and particularly plasmalogens, and LCPUFAs at various stages of diabetic retinopathy in humans.We performed lipidomic analyses on red blood cell membranes from controls and mainly type 2 diabetes mellitus patients with or without retinopathy. The fatty acid composition of erythrocytes was determined by gas chromatography and the phospholipid structure was determined by liquid chromatography equipped with an electrospray ionisation source and coupled with a tandem mass spectrometer (LC-ESI-MS/MS. A significant decrease in levels of docosahexaenoic acid and arachidonic acid in erythrocytes of diabetic patients with or without retinopathy was observed. The origin of this decrease was a loss of phosphatidyl-ethanolamine phospholipids esterified with these LCPUFAs. In diabetic patients without retinopathy, this change was balanced by an increase in the levels of several phosphatidyl-choline species. No influence of diabetes nor of diabetic retinopathy was observed on the concentrations of plasmalogen-type phospholipids.Diabetes and diabetic retinopathy were associated with a reduction of erythrocyte LCPUFAs in phosphatidyl-ethanolamines. The increase of the amounts of phosphatidyl-choline species in erythrocytes of diabetic patients without diabetic retinopathy might be a compensatory mechanism for the loss of LC-PUFA-rich phosphatidyl-ethanolamines.

  6. Degradation of cholesterol crystals in macrophages: the role of phospholipids

    Science.gov (United States)

    Koren, Eugen; Koscec, Mirna; Fugate, Robert D.

    1991-05-01

    Previous studies from this laboratory demonstrated degradation of cholesterol crystals ingested by macrophages in a cell culture system. Those studies also indicated that intracellular phospholipids could play an important role in mobilization of crystalline cholesterol. The purpose of this study was to further explore the role of each of the three major intracellular phospholipid species in degradation of crystals. Fluorescently labeled cholesterol crystals were incubated with phospholipids over a period of 5 days. Morphological changes in crystals were monitored by the use of digital imaging fluorescence microscopy, fluorescence redistribution after photobleaching, confocal microscopy, as well as epifluorescent and phase contrast microscopy. Results clearly demonstrated that all three phospholipids were able to mobilize crystalline cholesterol; however, mechanisms by which they exerted mobilization were different. Sphingomyelin and phosphatidylcholine were found to cause gradual and uniform dissolution of crystals, more or less preserving their original shape. Phosphatidylethanolamine appeared to penetrate into the crystal, causing its fragmentation and solubilization. In the mixture of all three phospholipids representing the composition found in macrophages, both of the described mechanisms were working simultaneously.

  7. Biochemical Markers of Joint Tissue Turnover

    DEFF Research Database (Denmark)

    Bay-Jensen, Anne-Christine; Sondergaard, Bodil Cecilie; Christiansen, Claus;

    2009-01-01

    Recent disappointments in late stage developments of anti-osteoarthritic drugs have reinforced efforts to develop better biomarkers for application in both the drug development process as well as in the routine management of these patients. Here we provide a brief review of biochemical tests...... available for the study of tissue turnover in each of the three compartments of the articular joint, that is the bone, the cartilage, and the synovium. Finally, we provide some perspective to future developments in biomarker discovery and discuss the potential impact such technologies could have on the drug...

  8. Effects of Dimethyl Sulfoxide on Surface Water near Phospholipid Bilayers.

    Science.gov (United States)

    Lee, Yuno; Pincus, Philip A; Hyeon, Changbong

    2016-12-06

    Despite much effort to probe the properties of dimethyl sulfoxide (DMSO) solution, the effects of DMSO on water, especially near plasma membrane surfaces, still remain elusive. By performing molecular dynamics simulations at varying DMSO concentrations (XDMSO), we study how DMSO affects structural and dynamical properties of water in the vicinity of phospholipid bilayers. As proposed by a number of experiments, our simulations confirm that DMSO induces dehydration from bilayer surfaces and disrupts the H-bond structure of water. However, DMSO-enhanced water diffusivity at solvent-bilayer interfaces, an intriguing discovery reported by a spin-label measurement, is not confirmed in our simulations. To resolve this discrepancy, we examine the location of the spin label (Tempo) relative to the solvent-bilayer interface. In accord with the evidence in the literature, our simulations, which explicitly model Tempo-phosphatidylcholine, find that the Tempo moiety is equilibrated at ∼8-10 Å below the bilayer surface. Furthermore, the DMSO-enhanced surface-water diffusion is confirmed only when water diffusion is analyzed around the Tempo moiety that is immersed below the bilayer surface, which implies that the experimentally detected signal of water using Tempo stems from the interior of bilayers, not from the interface. Our analysis finds that the increase of water diffusion below the bilayer surface is coupled to the increase of area per lipid with an increasing XDMSO(≲10mol%). Underscoring the hydrophobic nature of the Tempo moiety, our study calls for careful re-evaluation of the use of Tempo in measurements on lipid bilayer surfaces. Copyright © 2016 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  9. [Tracheal phospholipid composition and respiratory distress syndrome of the newborn].

    Science.gov (United States)

    Obladen, M

    1979-03-01

    Tracheal or pharyngeal aspirates were collected in 50 newborn infants with and without respiratory distress syndrome (RDS). After lipid extraction the phospholipids were analyzed with 2-dimensional thin layer chromatography. Surface-active are lecithin (PC), phosphatidylglycerol (PG), and phosphatidylinositol (PI). Newborn infants with RDS always have a complete lack of PG, which makes up to 11% of phospholipid-phosphors in mature newborns. In all infants with and without RDS, a sharp increase of PC occurs in the lung effluent after birth. The recovery from RDS is characterized by marked changes of PI: this phospholipid rises up to twice its initial value if the infants survive. The PI-increase parallels the clinical improvement and reaches its maximum usually on the 5th day of life. At the time of the PI-peak, the infants' surfactant function is sufficient to maintain alveolar stability with spontaneous breathing. In infants dying from RDS the PI-increase was not observed.

  10. Possible mechanism of adhesion in a mica supported phospholipid bilayer

    Energy Technology Data Exchange (ETDEWEB)

    Pertsin, Alexander, E-mail: ig3@ix.urz.uni-heidelberg.de [Angewandte Physikalische Chemie, Universität Heidelberg, Im Neuenheimer Feld 253, 69120 Heidelberg (Germany); Institute of Organo-Element Compounds, Russian Academy of Sciences, Vavilov Str. 28, 117991 Moscow (Russian Federation); Grunze, Michael [Angewandte Physikalische Chemie, Universität Heidelberg, Im Neuenheimer Feld 253, 69120 Heidelberg (Germany); Institute for Functional Interfaces, Karlsruhe Institute of Technology, Hermann-von- Helmholtz-Platz 1, 76344 Eggenstein-Leopoldshafen (Germany)

    2014-05-14

    Phospholipid bilayers supported on hydrophilic solids like silica and mica play a substantial role in fundamental studies and technological applications of phospholipid membranes. In both cases the molecular mechanism of adhesion between the bilayer and the support is of primary interest. Since the possibilities of experimental methods in this specific area are rather limited, the methods of computer simulation acquire great importance. In this paper we use the grand canonical Monte Carlo technique and an atomistic force field to simulate the behavior of a mica supported phospholipid bilayer in pure water as a function of the distance between the bilayer and the support. The simulation reveals a possible adhesion mechanism, where the adhesion is due to individual lipid molecules that protrude from the bilayer and form widely spaced links with the support. Simultaneously, the bilayer remains separated from the bilayer by a thin water interlayer which maintains the bilayer fluidity.

  11. Neutron diffraction studies of amphipathic helices in phospholipid bilayers

    Energy Technology Data Exchange (ETDEWEB)

    Bradshaw, J.P.; Gilchrist, P.J. [Univ. of Edinburgh (United Kingdom); Duff, K.C. [Univ. of Edinburgh Medical School (United Kingdom); Saxena, A.M. [Brookhaven National Laboratory, Upton, NY (United States)

    1994-12-31

    The structural feature which is thought to facilitate the interaction of many peptides with phospholipid bilayers is the ability to fold into an amphipathic helix. In most cases the exact location and orientation of this helix with respect to the membrane is not known, and may vary with factors such as pH and phospholipid content of the bilayer. The growing interest in this area is stimulated by indications that similar interactions can contribute to the binding of certain hormones to their cell-surface receptors. We have been using the techniques of neutron diffraction from stacked phospholipid bilayers in an attempt to investigate this phenomenon with a number of membrane-active peptides. Here we report some of our findings with three of these: the bee venom melittin; the hormone calcitonin; and a synthetic peptide representing the ion channel fragment of influenza A M2 protein.

  12. Pitfalls in quantifying species turnover: the residency effect

    OpenAIRE

    Kevin Chase Burns

    2014-01-01

    The composition of ecological communities changes continuously through time and space. Understanding this turnover in species composition is a central goal in biogeography, but quantifying species turnover can be problematic. Here, I describe an underappreciated source of bias in quantifying species turnover, namely ‘the residency effect’, which occurs when the contiguous distributions of species across sampling domains are small relative to census intervals. I present the results of a simula...

  13. NMR analyses of deuterated phospholipids isolated from Pichia angusta

    Science.gov (United States)

    Massou, S.; Augé, S.; Tropis, M.; Lindley, N. D.; Milon, A.

    1998-02-01

    The phospholipid composition of methylotrophic yeasts grown on deuterated and hydrogenated media has been determined by proton and phosphorus NMR. By using a line narrowing solvent, we could obtain linewidth lower than 2 Hz, and all the resonances could be resolved. Phospholipids were identified on the basis of their chemical shift and by 31P - H correlations (HMQC - HOHAHA gradient enhanced experiments). We have thus analysed qualitatively and quantitatively lipids mixtures directly after chloroform-methanol extraction. The lipid composition is deeply modified after growth in deuterated medium were phosphatidyl Inositol (PI) becomes the major lipid, instead of a PC, PS, PI mixture in hydrogenated conditions. La composition en phospholipides de levures méthylotrophes ayant poussé sur des milieux de cultures hydrogénés et deutériés a été déterminée par RMN du proton et du phosphore31. L'utilisation d'un solvant d'affinement a permis d'obtenir des largeurs de raies inférieures à 2Hz et de résoudre toutes les classes de phospholipides. Ils sont ensuite identifiés par leur déplacement chimique et par des corrélations phosphore - proton spécifiques (expériences HMQC-HOHAHA gradients). Cette approche a permis une analyse qualitative et quantitative de mélanges de phospholipides directement après extraction au chloroforme-méthanol. La composition en phospholipides est profondément modifiée lors de la croissance en milieu perdeutérié où l'on observe un lipide majoritaire, le phosphatidyl Inositol (PI), au lieu d'un mélange PC, PS PI en milieu hydrogéné.

  14. Fat lowers fat: purified phospholipids as emerging therapies for dyslipidemia.

    Science.gov (United States)

    Sahebkar, Amirhossein

    2013-04-01

    Dyslipidemia is a major coronary heart disease (CHD) risk factor. In spite of the proven efficacy of statin drugs in reducing CHD burden, there is still much room for the discovery of novel therapeutic agents to address the considerable residual cardiovascular risk that remains after treatment with currently available medications. In particular, there is an urgent demand for drugs capable of boosting the concentration and/or function of high-density lipoprotein (HDL) and apolipoprotein A-I (apo A-I), thereby promoting reverse cholesterol transport. Phospholipids are naturally occurring fats that play indispensible role in human health via their structural, energy storage, signal transduction and metabolic functions. Supplementation with either purified or mixed preparations of bioactive phospholipids has been reported to ameliorate a range of nutritional and cardiovascular disorders. Moreover, several lines of evidence have supported the efficacy of dietary phospholipids in reducing serum and hepatic contents of cholesterol and triglycerides, while increasing HDL-C and apo A-I levels. These beneficial effects of phospholipids could be attributed to their ability in reducing intestinal cholesterol absorption, enhancing biliary cholesterol excretion and modulating the expression and activity of transcriptional factors and enzymes that are involved in lipoprotein metabolism. Given their extreme safety and biocompatibility, dietary supplementation with phospholipid preparations, in particular phosphatidylinositol, appears as a novel and effective strategy that could be used as an alternative or adjunctive therapy to the current medications. The present review outlines the in-vitro, in-vivo and clinical findings on the anti-dyslipidemic effects of three most abundant phospholipids in the human body and diet namely phosphatidylcholine, phosphatidylethanolamine and phosphatidylinositol.

  15. Membrane potential modulates plasma membrane phospholipid dynamics and K-Ras signaling

    Science.gov (United States)

    Zhou, Yong; Wong, Ching-On; Cho, Kwang-jin; van der Hoeven, Dharini; Liang, Hong; Thakur, Dhananiay P.; Luo, Jialie; Babic, Milos; Zinsmaier, Konrad E.; Zhu, Michael X.; Hu, Hongzhen; Venkatachalam, Kartik; Hancock, John F.

    2015-01-01

    Plasma membrane depolarization can trigger cell proliferation, but how membrane potential influences mitogenic signaling is uncertain. Here, we show that plasma membrane depolarization induces nanoscale reorganization of phosphatidylserine and phosphatidylinositol 4,5-bisphosphate but not other anionic phospholipids. K-Ras, which is targeted to the plasma membrane by electrostatic interactions with phosphatidylserine, in turn undergoes enhanced nanoclustering. Depolarization-induced changes in phosphatidylserine and K-Ras plasma membrane organization occur in fibroblasts, excitable neuroblastoma cells, and Drosophila neurons in vivo and robustly amplify K-Ras–dependent mitogen-activated protein kinase (MAPK) signaling. Conversely, plasma membrane repolarization disrupts K-Ras nanoclustering and inhibits MAPK signaling. By responding to voltage-induced changes in phosphatidylserine spatiotemporal dynamics, K-Ras nanoclusters set up the plasma membrane as a biological field-effect transistor, allowing membrane potential to control the gain in mitogenic signaling circuits. PMID:26293964

  16. Endogenous Turnover of Cyanogenic Glycosides in Plants

    DEFF Research Database (Denmark)

    Picmanova, Martina

    Amongst the vast multitude of plant secondary metabolites, cyanogenic glycosides (CNglcs) occupy an important place as sophisticated defence compounds, releasing toxic hydrogen cyanide (HCN) upon herbivore attack – a process known as cyanogenesis. Beside this wellestablished function, there is st......Amongst the vast multitude of plant secondary metabolites, cyanogenic glycosides (CNglcs) occupy an important place as sophisticated defence compounds, releasing toxic hydrogen cyanide (HCN) upon herbivore attack – a process known as cyanogenesis. Beside this wellestablished function...... through the formation of β- cyanoalanine, or, potentially, in an alternative endogenous turnover pathway circumventing the release of HCN. The investigation of the latter is the primary focus of this PhD project. Scattered data from the literature indicated that CNglcs co-occur in plants...... revealed the formation of glycosides of amides, carboxylic acids and "anitriles", including their di- and triglycosides, evidently derived from CNglcs. Based on results common to the three phylogenetically unrelated plant species, a recycling endogenous turnover pathway for CNglcs was suggested in which...

  17. Dynamics of Adipocyte Turnover in Humans

    Energy Technology Data Exchange (ETDEWEB)

    Spalding, K; Arner, E; Westermark, P; Bernard, S; Buchholz, B; Bergmann, O; Blomqvist, L; Hoffstedt, J; Naslund, E; Britton, T; Concha, H; Hassan, M; Ryden, M; Frisen, J; Arner, P

    2007-07-16

    Obesity is increasing in an epidemic fashion in most countries and constitutes a public health problem by enhancing the risk for cardiovascular disease and metabolic disorders such as type 2 diabetes. Owing to the increase in obesity, life expectancy may start to decrease in developed countries for the first time in recent history. The factors determining fat mass in adult humans are not fully understood, but increased lipid storage in already developed fat cells is thought to be most important. We show that adipocyte number is a major determinant for the fat mass in adults. However, the number of fat cells stays constant in adulthood in lean and obese and even under extreme conditions, indicating that the number of adipocytes is set during childhood and adolescence. To establish the dynamics within the stable population of adipocytes in adults, we have measured adipocyte turnover by analyzing the integration of {sup 14}C derived from nuclear bomb tests in genomic DNA. Approximately 10% of fat cells are renewed annually at all adult ages and levels of body mass index. Neither adipocyte death nor generation rate is altered in obesity, suggesting a tight regulation of fat cell number that is independent of metabolic profile in adulthood. The high turnover of adipocytes establishes a new therapeutic target for pharmacological intervention in obesity.

  18. Endocrine and pharmacological suppressors of bone turnover protect against osteopenia in ovariectomized rats.

    Science.gov (United States)

    Wronski, T J; Dann, L M; Scott, K S; Crooke, L R

    1989-08-01

    This study was designed to test the hypothesis that endocrine and pharmacological suppressors of bone turnover prevent the development of osteopenia during estrogen deficiency. Sham-operated control and ovariectomized (OVX) rats were treated intermittently with vehicle alone, estrogen, or the diphosphonate compounds etidronate disodium (EHDP) and NE-58095 [2-(3-pyridinyl)2-hydroxyethylidene-1,1-bisphosphonate disodium] for 35 or 70 days after surgery. Their proximal tibiae were processed undecalcified for quantitative bone histomorphometry. Vehicle-treated OVX rats were characterized by decreased cancellous bone volume and 3- to 4-fold increases in osteoblast surface, osteoclast surface, bone formation rate, and bone resorption rate. Treatment of OVX rats with estrogen and NE-58095 provided complete protection against bone loss and significantly depressed all of the above indices of bone turnover. OVX rats treated with EHDP exhibited at least partial protection against bone loss and decreased bone turnover. EHDP induced a mild mineralization defect, as indicated by a prolonged mineralization lag time at the tibial endocortical surface. The new diphosphonate compound NE-58095 did not impair bone mineralization. Our results indicate that endocrine and pharmacological suppressors of bone turnover prevent the development of osteopenia during the early stages of estrogen deficiency. If confirmed by clinical trials in humans, diphosphonate compounds may prove to be an alternative to estrogen for the prevention of postmenopausal bone loss.

  19. Impact of reticulated platelets on antiplatelet response to thienopyridines is independent of platelet turnover.

    Science.gov (United States)

    Stratz, Christian; Nührenberg, Thomas; Amann, Michael; Cederqvist, Marco; Kleiner, Pascal; Valina, Christian M; Trenk, Dietmar; Neumann, Franz-Josef; Hochholzer, Willibald

    2016-10-28

    Reticulated platelets are associated with impaired antiplatelet response to thienopyridines. It is uncertain whether this interaction is caused by a decreased drug exposure due to high platelet turnover reflected by elevated levels of reticulated platelets or by intrinsic properties of reticulated platelets. This study sought to investigate if the impact of reticulated platelets on early antiplatelet response to thienopyridines is mainly caused by platelet turnover as previously suggested. Elective patients undergoing coronary intervention were randomised to loading with clopidogrel 600 mg or prasugrel 60 mg (n=200). Adenosine diphosphate (ADP)-induced platelet reactivity was determined by impedance aggregometry before, at 30, 60, 90, and 120 minutes and at day 1 after loading. Immature platelet count was assessed as marker of reticulated platelets by flow cytometry. Platelet reactivity increased with rising levels of immature platelet count in both groups. This effect was more distinctive in patients on clopidogrel as compared to patients on prasugrel. Overall, immature platelet count correlated well with on-treatment platelet reactivity at all time-points (p < 0.001). These correlations did not change over time in the entire cohort as well as in patients treated with clopidogrel or prasugrel indicating an effect independent of platelet turnover (comparison of correlations 120 minutes/day 1: p = 0.64). In conclusion, the association of immature platelet count with impaired antiplatelet response to thienopyridines is similar early and late after loading. This finding suggests as main underlying mechanism another effect of reticulated platelets on thienopyridines than platelet turnover.

  20. Strategies for adapting to high rates of employee turnover.

    Science.gov (United States)

    Mowday, R T

    1984-01-01

    For many organizations facing high rates of employee turnover, strategies for increasing employee retention may not be practical because employees leave for reasons beyond the control of management or the costs of reducing turnover exceed the benefits to be derived. In this situation managers need to consider strategies that can minimize or buffer the organization from the negative consequences that often follow from turnover. Strategies organizations can use to adapt to uncontrollably high employee turnover rates are presented in this article. In addition, suggestions are made for how managers should make choices among the alternative strategies.

  1. Role of inositol phospholipid signaling in natural killer cell biology

    Directory of Open Access Journals (Sweden)

    Matthew eGumbleton

    2013-03-01

    Full Text Available Natural Killer (NK cells are important in the host defense against malignancy and infection. At a cellular level NK cells are activated when signals from activating receptors exceed signaling from inhibitory receptors. At a molecular level NK cells undergo an education process to prevent autoimmunity. Mouse models have shown important roles for inositol phospholipid signaling in lymphocytes. NK cells from mice with deletion in different members of the PI3K signaling pathway have defective development, natural killer cell repertoire expression (NKRR and effector function. Here we review the role of inositol phospholipid signaling in NK cell biology.

  2. Genetic Analysis of Digestive Physiology Using Fluorescent Phospholipid Reporters

    Science.gov (United States)

    Farber, Steven A.; Pack, Michael; Ho, Shiu-Ying; Johnson, Iain D.; Wagner, Daniel S.; Dosch, Roland; Mullins, Mary C.; Hendrickson, H. Stewart; Hendrickson, Elizabeth K.; Halpern, Marnie E.

    2001-05-01

    Zebrafish are a valuable model for mammalian lipid metabolism; larvae process lipids similarly through the intestine and hepatobiliary system and respond to drugs that block cholesterol synthesis in humans. After ingestion of fluorescently quenched phospholipids, endogenous lipase activity and rapid transport of cleavage products results in intense gall bladder fluorescence. Genetic screening identifies zebrafish mutants, such as fat free, that show normal digestive organ morphology but severely reduced phospholipid and cholesterol processing. Thus, fluorescent lipids provide a sensitive readout of lipid metabolism and are a powerful tool for identifying genes that mediate vertebrate digestive physiology.

  3. Regulation of inositol phospholipid binding and signaling through syndecan-4

    DEFF Research Database (Denmark)

    Couchman, John R; Vogt, Susan; Lim, Ssang-Taek

    2002-01-01

    inositol phospholipids. In turn, lipid binding stabilizes the syndecan in oligomeric form, with subsequent binding and activation of protein kinase C. The specificity of phospholipid binding and its potential regulation are investigated here. Highest affinity of the syndecan-4 cytoplasmic domain was seen......-regulator of syndecan-4 signaling. Similarly, phosphorylation of serine 183 in syndecan-4 cytoplasmic domain reduced PtdIns(4,5)P(2) binding affinity by over 100-fold, although interaction could still be detected by nuclear magnetic resonance spectroscopy. Only protein kinase Calpha was up-regulated in activity...

  4. Turnover intentions and voluntary turnover: the moderating roles of self-monitoring, locus of control, proactive personality, and risk aversion.

    Science.gov (United States)

    Allen, David G; Weeks, Kelly P; Moffitt, Karen R

    2005-09-01

    This article explores moderators of the relationship between turnover intentions and turnover behavior to better explain why some employees translate intentions into behavior and other employees do not. Individual differences in self-monitoring, locus of control, proactive personality, and risk aversion were examined. Results indicate that self-monitoring and risk aversion moderate the intentions-turnover link. Specifically, the relationship between turnover intentions and turnover is stronger for low self-monitors and those lower in risk aversion. Locus of control moderated the relationship in 1 of 2 samples such that the relationship was stronger for those with an internal locus of control. Proactive personality, however, did not directly moderate the relationship between intentions and turnover behaviors.

  5. Biosynthetic labeling and two-color imaging of phospholipids in cells.

    Science.gov (United States)

    Jao, Cindy Y; Roth, Mary; Welti, Ruth; Salic, Adrian

    2015-02-09

    Phospholipids with a choline head group are abundant components of all biological membranes, performing critical functions in cellular structure, metabolism, and signaling. In spite of their importance, our ability to visualize choline phospholipids in vivo remains very limited. We present a simple and robust chemical strategy to image choline phospholipids, based on the metabolic incorporation of azidocholine analogues, that accurately reflects the normal biosynthetic incorporation of choline into cellular phospholipids. Azidocholine-labeled phospholipids can be imaged in cells with high sensitivity and resolution, following derivatization with fluorophores, by bio-orthogonal chemical reactions compatible with live-cell imaging. We used this method to visualize the subcellular localization of choline phospholipids. We also demonstrate that double metabolic labeling with azidocholine and propargylcholine allows sensitive two-color imaging of choline phospholipids. Our method represents a powerful approach to directly image phospholipids, and to study their dynamics in cells and tissues.

  6. Estrogen regulates the rate of bone turnover but bone balance in ovariectomized rats is modulated by prevailing mechanical strain

    Science.gov (United States)

    Westerlind, K. C.; Wronski, T. J.; Ritman, E. L.; Luo, Z. P.; An, K. N.; Bell, N. H.; Turner, R. T.

    1997-01-01

    Estrogen deficiency induced bone loss is associated with increased bone turnover in rats and humans. The respective roles of increased bone turnover and altered balance between bone formation and bone resorption in mediating estrogen deficiency-induced cancellous bone loss was investigated in ovariectomized rats. Ovariectomy resulted in increased bone turnover in the distal femur. However, cancellous bone was preferentially lost in the metaphysis, a site that normally experiences low strain energy. No bone loss was observed in the epiphysis, a site experiencing higher strain energy. The role of mechanical strain in maintaining bone balance was investigated by altering the strain history. Mechanical strain was increased and decreased in long bones of ovariectomized rats by treadmill exercise and functional unloading, respectively. Functional unloading was achieved during orbital spaceflight and following unilateral sciatic neurotomy. Increasing mechanical loading reduced bone loss in the metaphysis. In contrast, decreasing loading accentuated bone loss in the metaphysis and resulted in bone loss in the epiphysis. Finally, administration of estrogen to ovariectomized rats reduced bone loss in the unloaded and prevented loss in the loaded limb following unilateral sciatic neurotomy in part by reducing indices of bone turnover. These results suggest that estrogen regulates the rate of bone turnover, but the overall balance between bone formation and bone resorption is influenced by prevailing levels of mechanical strain.

  7. Combined effect of sesamin and soybean phospholipid on hepatic fatty acid metabolism in rats

    OpenAIRE

    Ide, Takashi

    2014-01-01

    We studied the combined effect of sesamin (1:1 mixture of sesamin and episesamine) and soybean phospholipid on lipid metabolism in rats. Male rats were fed diets supplemented with 0 or 2 g/kg sesamin, and containing 0 or 50 g/kg soybean phospholipid, for 19 days. Sesamin and soybean phospholipid decreased serum triacylglycerol concentrations and the combination of these compounds further decreased the parameter in an additive fashion. Soybean phospholipid but not sesamin reduced the hepatic c...

  8. 一种独特的仿生磷脂--Phospholipid(R)CDM%Unique biomimetic phospholipid complex--Phospholipid (R) CDM

    Institute of Scientific and Technical Information of China (English)

    周华隆

    2005-01-01

    Phospholipid(R)CDM是来源于椰子油的一种多功能的仿生磷脂产品,具有温和的清洁性、良好的亲和性以及防腐增效作用,甚至可用作无防腐剂产品中,在个人护理品中用途广泛.

  9. Development of polyherbal antidiabetic formulation encapsulated in the phospholipids vesicle system

    Directory of Open Access Journals (Sweden)

    Vinod Kumar Gauttam

    2013-01-01

    Full Text Available Multifactorial metabolic diseases, for instance diabetes develop several complications like hyperlipidemia, hepatic toxicity, immunodeficiency etc., Hence, instead of mono-drug therapy the management of the disease requires the combination of herbs. Marketed herbal drugs comprise of irrational combinations, which makes their quality control more difficult. Phytoconstituents, despite having excellent bioactivity in vitro demonstrate less or no in vivo actions due to their poor lipid solubility, resulting in high therapeutic dose regimen; phospholipids encapsulation can overcome this problem. Hence, present study was designed to develop a phospholipids encapsulated polyherbal anti-diabetic formulation. In the present study, polyherbal formulation comprises of lyophilized hydro-alcoholic (50% v/v extracts of Momordica charantia, Trigonella foenum-graecum and Withania somnifera 2:2:1, respectively, named HA, optimized based on oral glucose tolerance test model in normal Wistar rats. The optimized formulation (HA entrapped in the phosphatidylcholine and cholesterol (8:2 vesicle system is named HA lipids (HAL. The vesicles were characterized for shape, morphology, entrapment efficiency, polar-dispersity index and release profile in the gastric pH. The antidiabetic potential of HA, marketed polyherbal formulation (D-fit and HAL was compared in streptozotocin-induced diabetic rat model of 21 days study. The parameters evaluated were behavioral changes, body weight, serum glucose level, lipid profile and oxidative stress. The antidiabetic potential of HA (1000 mg/kg was at par with the D-fit (1000 mg/kg. However, the potential was enhanced by phospholipids encapsulation; as HAL (500 mg/kg has shown more significant (P < 0.05 potential in comparison to HA (1000 mg/kg and at par with metformin (500 mg/kg.

  10. Phosphocreatine interacts with phospholipids, affects membrane properties and exerts membrane-protective effects.

    Directory of Open Access Journals (Sweden)

    Malgorzata Tokarska-Schlattner

    Full Text Available A broad spectrum of beneficial effects has been ascribed to creatine (Cr, phosphocreatine (PCr and their cyclic analogues cyclo-(cCr and phospho-cyclocreatine (PcCr. Cr is widely used as nutritional supplement in sports and increasingly also as adjuvant treatment for pathologies such as myopathies and a plethora of neurodegenerative diseases. Additionally, Cr and its cyclic analogues have been proposed for anti-cancer treatment. The mechanisms involved in these pleiotropic effects are still controversial and far from being understood. The reversible conversion of Cr and ATP into PCr and ADP by creatine kinase, generating highly diffusible PCr energy reserves, is certainly an important element. However, some protective effects of Cr and analogues cannot be satisfactorily explained solely by effects on the cellular energy state. Here we used mainly liposome model systems to provide evidence for interaction of PCr and PcCr with different zwitterionic phospholipids by applying four independent, complementary biochemical and biophysical assays: (i chemical binding assay, (ii surface plasmon resonance spectroscopy (SPR, (iii solid-state (31P-NMR, and (iv differential scanning calorimetry (DSC. SPR revealed low affinity PCr/phospholipid interaction that additionally induced changes in liposome shape as indicated by NMR and SPR. Additionally, DSC revealed evidence for membrane packing effects by PCr, as seen by altered lipid phase transition. Finally, PCr efficiently protected against membrane permeabilization in two different model systems: liposome-permeabilization by the membrane-active peptide melittin, and erythrocyte hemolysis by the oxidative drug doxorubicin, hypoosmotic stress or the mild detergent saponin. These findings suggest a new molecular basis for non-energy related functions of PCr and its cyclic analogue. PCr/phospholipid interaction and alteration of membrane structure may not only protect cellular membranes against various insults

  11. Role of phospholipids in the pathophysiology of the gut-liver axis

    NARCIS (Netherlands)

    Petruzzelli, M.

    2010-01-01

    Phospholipids represent essential components of bile. Together with bile acids and cholesterol, phospholipids form “mixed micelles”. If sufficient amounts of phospholipids are available, no simple bile acid micelles are present, with prevention of bile acid toxicity and cholesterol crystallization.

  12. Role of phospholipids in the pathophysiology of the gut-liver axis

    NARCIS (Netherlands)

    Petruzzelli, M.

    2010-01-01

    Phospholipids represent essential components of bile. Together with bile acids and cholesterol, phospholipids form “mixed micelles”. If sufficient amounts of phospholipids are available, no simple bile acid micelles are present, with prevention of bile acid toxicity and cholesterol crystallization.

  13. Advances in studies of phospholipids as carriers in skin topical application

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective:This article provides an overview of characteristics of phospholipids,the characteristics and influential factors of liposome and microemulsion as carriers for skin delivery of drugs,and the latest advances of the phospholipids carriers in transdermal delivery systems.The perspective is that phospholipids carriers may be capable of a wide range of applications in the transdermal defivery system.

  14. Dynamic phospholipid signaling by G protein-coupled receptors

    NARCIS (Netherlands)

    Weernink, Paschal A. Oude; Han, Li; Jakobs, Karl H.; Schmidt, Martina

    2007-01-01

    G protein-coupled receptors (GPCRs) control a variety of fundamental cellular processes by regulating phospholipid signaling pathways. Essential for signaling by a large number of receptors is the hydrolysis of the membrane phosphoinositide PIP2 by phospholipase C (PLC) into the second messengers IP

  15. Characterization of associated proteins and phospholipids in natural rubber latex.

    Science.gov (United States)

    Sansatsadeekul, Jitlada; Sakdapipanich, Jitladda; Rojruthai, Porntip

    2011-06-01

    Non-rubber components present in natural rubber (NR) latex, such as proteins and phospholipids, are presumed to be distributed in the serum fraction as well as surrounding the rubber particle surface. The phospholipid-protein layers covering the rubber particle surface are especially interesting due to their ability to enhance the colloidal stability of NR latex. In this study, we have characterized the components surrounding the NR particle surface and investigated their role in the colloidal stability of NR particles. Proteins from the cream fraction were proteolytically removed from the NR latex and compare to those from the serum fractions using SDS-polyacrylamide gel electrophoresis revealing that both fractions contained similar proteins in certain molecular weights such as 14.5, 25 and 27 kDa. Phospholipids removed from latex by treatment with NaOH were analyzed using (1)H-NMR spectroscopy and several major signals were assignable to -(CH(2))(n)-, -CH(2)OP, -CH(2)OC═O and -OCH(2)CH(2)NH-. These signals are important evidence that indicates phospholipids associate with the rubber chain. The colloidal behavior of rubber lattices before and after removal of protein-lipid membrane was evaluated by zeta potential analysis and scanning electron microscope (SEM). The lowest zeta potential value of NR particles was observed at pH 10, consequently leading to the highest stability of rubber particles. Additionally, SEM micrographs clearly displayed a gray ring near the particle surface corresponding to the protein-lipid membrane layer.

  16. Phospholipid bilayer formation at a bare Si surface

    DEFF Research Database (Denmark)

    Gutberlet, T.; Steitz, R.; Fragneto, G.

    2004-01-01

    Neutron reflectivity was applied to monitor in situ the adsorption of small unilamellar phospholipid vesicles on a solid bare hydrophilic Si interface. The obtained reflectivity curves are consistent with the rupture and fusion model for the adsorption of phosphatidylcholine vesicles to solid...

  17. Phospholipid organization in monkey erythrocytes upon Plasmodium knowlesi infection

    NARCIS (Netherlands)

    Schaft, P.H. van der; Beaumelle, B.; Vial, H.; Roelofsen, B.; Kamp, J.A.F. op den; Deenen, L.L.M. van

    1987-01-01

    The phospholipid organization in monkey erythrocytes upon Plasmodium knowlesi infection has been studied. Parasitized and nonparasitized erythrocytes from malaria-infected blood were separated and pure erythrocyte membranes from parasitized cells were isolated using Affi-Gel beads. In this way, the

  18. Evaluation of phospholipid transfer protein as a therapeutic target

    NARCIS (Netherlands)

    Vergeer, Menno; Dallinga-Thie, Gessje M.; Dullaart, Robin P. F.; Van Tol, Arie

    2008-01-01

    Phospholipid transfer protein (PLTP) plays an essential role in lipoprotein metabolism. Deficiency or overexpression of PUP in animal models results in modulation of the atherosclerotic process. Moreover, PUP has also been implicated in obesity and diabetes, underscoring its versatile nature and its

  19. Evaluation of phospholipid transfer protein as a therapeutic target

    NARCIS (Netherlands)

    M. Vergeer (Menno); G.M. Dallinga-Thie (Geesje); R.P.F. Dullaart (Robin); A. van Tol (Arie)

    2008-01-01

    textabstractPhospholipid transfer protein (PLTP) plays an essential role in lipoprotein metabolism. Deficiency or overexpression of PLTP in animal models results in modulation of the atherosclerotic process. Moreover, PLTP has also been implicated in obesity and diabetes, underscoring its versatile

  20. Enzyme catalysed production of phospholipids with modified fatty acid profile

    DEFF Research Database (Denmark)

    Vikbjerg, Anders Falk

    2006-01-01

    Phospholipider har stor anvendelse i levnedsmiddel-, kosmetik-, og farmaceutiske produkter for blandt andet deres emulgerende egenskaber samt evne til at danne liposomer. Interessen for at ændre på phospholipidernes struktur er stigende. Strukturændringer resulterer i ændret funktionalitet. Ved u...

  1. PHOSPHOLIPIDS OF FIVE PSEUDOMONAD ARCHETYPES FOR DIFFERENT TOLUENE DEGRADATION PATHWAYS

    Science.gov (United States)

    Liquid chromatography/electrospray ionization/mass spectrometry (LC/ESI/MS) was used to determine phospholipid profiles for five reference pseudomonad strains harboring distinct toluene catabolic pathways: Pseudomonas putida mt-2, Pseudomonas putida F1, Burkholderia cepacia G4, B...

  2. Membrane Phospholipid Redistribution in Cytokinesis: A Theoretical Model

    Institute of Scientific and Technical Information of China (English)

    Mei-Wen AN; Wen-Zhou WU; Wei-Yi CHEN

    2005-01-01

    In cell mitosis, cytokinesis is a major deformation process, during which the site of the contractile ring is determined by the biochemical stimulus from asters of the mitotic apparatus, actin and myosin assembly is related to the motion of membrane phospholipids, and local distribution and arrangement of the microfilament cytoskeleton are different at different cytokinesis stages. Based on the Zinemanas-Nir model, a new model is proposed in this study to simulate the entire process by coupling the biochemical stimulus with the mechanical actions. There were three assumptions in this model: the movements of phospholipid proteins are driven by gradients of biochemical stimulus on the membrane surface; the local assembly of actin and myosin filament depends on the amount of phospholipid proteins at the same location;and the surface tension includes membrane tensions due to both the passive deformation of the membrane and the active contraction of actin filament, which is determined by microfilament redistribution and rearrangement. This model could explain the dynamic movement of microfilaments during cytokinesis and predict cell deformation. The calculated results from this model demonstrated that the reorientation of phospholipid proteins and the redistribution and reorientation of microfilaments may play a crucial role in cell division. This model may better represent the cytokinesis process by the introduction of biochemical stimulus.

  3. Phospholipid signaling responses in salt-stressed rice leaves

    NARCIS (Netherlands)

    Darwish, E.; Testerink, C.; Khalil, M.; El-Shihy, O.; Munnik, T.

    2009-01-01

    Salinity is one of the major environmental factors limiting growth and productivity of rice plants. In this study, the effect of salt stress on phospholipid signaling responses in rice leaves was investigated. Leaf cuts were radiolabeled with 32 P-orthophosphate and the lipids extracted and analyzed

  4. Mechanisms of anti-phospholipid antibody formation and action

    NARCIS (Netherlands)

    de Groot, Philip G.

    2011-01-01

    The antiphospholipid syndrome is an autoimmune disease characterised by the clinical features of recurrent thrombosis in the venous or arterial circulation and foetal losses in combination with circulating anti-phospholipid antibodies in the blood of the afflicted patients. Over the last 25 years nu

  5. 21 CFR 862.1575 - Phospholipid test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Phospholipid test system. 862.1575 Section 862.1575 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... treatment of disorders involving lipid (fat) metabolism. (b) Classification. Class I (general controls)....

  6. Dynamic combinatorial chemistry at the phospholipid bilayer interface

    NARCIS (Netherlands)

    Mansfeld, Friederike M.; Au-Yeung, Ho Yu; Sanders, Jeremy K.M.; Otto, Sijbren

    2010-01-01

    Background: Molecular recognition at the environment provided by the phospholipid bilayer interface plays an important role in biology and is subject of intense investigation. Dynamic combinatorial chemistry is a powerful approach for exploring molecular recognition, but has thus far not been

  7. Phospholipid Complex Technique for Superior Bioavailability of Phytoconstituents

    Directory of Open Access Journals (Sweden)

    Kattamanchi Gnananath

    2017-04-01

    Full Text Available Phytoconstituents have been utilized as medicines for thousands of years, yet their application is limited owing to major hurdles like deficit lipid solubility, large molecular size and degradation in the gastric environment of gut. Recently, phospholipid-complex technique has unveiled in addressing these stumbling blocks either by enhancing the solubilizing capacity or its potentiating ability to pass through the biological membranes and it also protects the active herbal components from degradation. Hence, this phospholipid-complex-technique can enable researchers to deliver the phytoconstituents into systemic circulation by using certain conventional dosage forms like tablets and capsules. This review highlights the unique property of phospholipids in drug delivery, their role as adjuvant in health benefits, and their application in the herbal medicine systems to improve the bioavailability of active herbal components. Also we summarize the prerequisites for phytosomes preparation like the selection of type of phytoconstituents, solvents used, various methods employed in phytosomal preparation and its characterization. Further we discuss the key findings of recent research work conducted on phospholipid-based delivery systems which can enable new directions and advancements to the development of herbal dosage forms.

  8. Prostaglandin phospholipid conjugates with unusual biophysical and cytotoxic properties

    DEFF Research Database (Denmark)

    Pedersen, Palle Jacob; Adolph, Sidsel K.; Andresen, Thomas Lars;

    2010-01-01

    The synthesis of two secretory phospholipase A(2) IIA sensitive 15-deoxy-Delta(12,14)-prostaglandin J(2) phospholipid conjugates is described and their biophysical and biological properties are reported. The conjugates spontaneously form particles in the liposome size region upon dispersion in an...

  9. Multi-isotope imaging mass spectrometry reveals slow protein turnover in hair-cell stereocilia.

    Science.gov (United States)

    Zhang, Duan-Sun; Piazza, Valeria; Perrin, Benjamin J; Rzadzinska, Agnieszka K; Poczatek, J Collin; Wang, Mei; Prosser, Haydn M; Ervasti, James M; Corey, David P; Lechene, Claude P

    2012-01-15

    Hair cells of the inner ear are not normally replaced during an animal's life, and must continually renew components of their various organelles. Among these are the stereocilia, each with a core of several hundred actin filaments that arise from their apical surfaces and that bear the mechanotransduction apparatus at their tips. Actin turnover in stereocilia has previously been studied by transfecting neonatal rat hair cells in culture with a β-actin-GFP fusion, and evidence was found that actin is replaced, from the top down, in 2-3 days. Overexpression of the actin-binding protein espin causes elongation of stereocilia within 12-24 hours, also suggesting rapid regulation of stereocilia lengths. Similarly, the mechanosensory 'tip links' are replaced in 5-10 hours after cleavage in chicken and mammalian hair cells. In contrast, turnover in chick stereocilia in vivo is much slower. It might be that only certain components of stereocilia turn over quickly, that rapid turnover occurs only in neonatal animals, only in culture, or only in response to a challenge like breakage or actin overexpression. Here we quantify protein turnover by feeding animals with a (15)N-labelled precursor amino acid and using multi-isotope imaging mass spectrometry to measure appearance of new protein. Surprisingly, in adult frogs and mice and in neonatal mice, in vivo and in vitro, the stereocilia were remarkably stable, incorporating newly synthesized protein at hair cells expressing β-actin-GFP we bleached fiducial lines across hair bundles, but they did not move in 6 days. When we stopped expression of β- or γ-actin with tamoxifen-inducible recombination, neither actin isoform left the stereocilia, except at the tips. Thus, rapid turnover in stereocilia occurs only at the tips and not by a treadmilling process.

  10. Bone mass and turnover in fibromyalgia

    DEFF Research Database (Denmark)

    Jacobsen, Søren; Gam, A; Egsmose, C

    1993-01-01

    Physical inactivity accelerates bone loss. Since patients with fibromyalgia are relatively physically inactive, bone mass and markers of bone metabolism were determined in 12 premenopausal women with fibromyalgia and in healthy age matched female control subjects. No differences were found...... in lumbar bone mineral density, femoral neck bone mineral density, serum levels of alkaline phosphatase, osteocalcin, ionized calcium and phosphate. The urinary excretion of both hydroxyproline and calcium relative to urinary creatinine excretion was significantly higher in patients with fibromyalgia, p = 0.......01. This was linked to lower urinary creatinine excretion (p = 0.02) probably reflecting lower physical activity in the patients with fibromyalgia. We conclude that bone mass and turnover are generally not affected in premenopausal women with fibromyalgia....

  11. Performance and turnover intentions: a social exchange perspective

    NARCIS (Netherlands)

    Biron, M.; Boon, C.

    2013-01-01

    Purpose - Prior research has yielded mixed results regarding the relationship between performance and turnover intentions. Drawing from social exchange theory, the purpose of this paper is to propose that the performance-turnover intentions association may be contingent upon individuals' exchange re

  12. Re-Examining the Relationship between Age and Voluntary Turnover

    Science.gov (United States)

    Ng, Thomas W. H.; Feldman, Daniel C.

    2009-01-01

    In their quantitative review of the literature, Healy, Lehman, and McDaniel [Healy, M. C., Lehman, M., & McDaniel, M. A. (1995). Age and voluntary turnover: A quantitative review. "Personnel Psychology, 48", 335-345] concluded that age is only weakly related to voluntary turnover (average r = -0.08). However, with the significant changes in…

  13. The Link between Training Satisfaction, Work Engagement and Turnover Intention

    Science.gov (United States)

    Memon, Mumtaz Ali; Salleh, Rohani; Baharom, Mohamed Noor Rosli

    2016-01-01

    Purpose: The purpose of this paper is to examine the casual relationship between training satisfaction, work engagement (WE) and turnover intention and the mediating role of WE between training satisfaction and turnover intention. Design/methodology/approach: Data were collected from 409 oil and gas professionals using an email survey…

  14. Organisational commitment and turnover intentions in humanitarian organisations

    NARCIS (Netherlands)

    Wijnmaalen, Julia; Heyse, Liesbet; Voordijk, Hans

    2016-01-01

    Unwanted staff turnover is a prominent HRM problem in humanitarian organisations. In the profit sector, HRM tools such as pay, benefits, socialisation and training have proven to be effective in increasing organisational commitment and decreasing staff turnover. This study explores whether such tool

  15. Organizational Characteristics Associated with Staff Turnover in Nursing Homes

    Science.gov (United States)

    Castle, Nicholas G.; Engberg, John

    2006-01-01

    Purpose: The association between certified nurse aide, licensed practical nurse, and registered nurse turnover and the organizational characteristics of nursing homes are examined. Design and Methods: Hypotheses for eight organizational characteristics are examined (staffing levels, top management turnover, resident case mix, facility quality,…

  16. Organizational commitment and turnover intentions in humanitarian organizations

    NARCIS (Netherlands)

    Wijnmalen, Julia; Heyse, Liesbet; Voordijk, Hans

    2016-01-01

    Unwanted staff turnover is a prominent HRM problem in humanitarian organisations. In the profit sector, HRM tools such as pay, benefits, socialisation and training have proven to be effective in increasing organisational commitment and decreasing staff turnover. This study explores whether such

  17. Organisational commitment and turnover intentions in humanitarian organisations

    NARCIS (Netherlands)

    Wijnmaalen, Julia; Heyse, Liesbet; Voordijk, Johannes T.

    2016-01-01

    Unwanted staff turnover is a prominent HRM problem in humanitarian organisations. In the profit sector, HRM tools such as pay, benefits, socialisation and training have proven to be effective in increasing organisational commitment and decreasing staff turnover. This study explores whether such

  18. Reducing staff turnover: a case study of dialysis facilities.

    Science.gov (United States)

    Tai, T W; Robinson, C D

    1998-01-01

    A multivariate logistic analysis of 42 Texas dialysis facilities indicated that younger, white, short tenure, an LVN/LPN, with less support from family and friends for emotional concerns, and less supervisor support significantly increased the likelihood of turnover (p staff turnover of these dialysis facilities increases costs and impedes the delivery of quality patient care. Managerial strategies to increase staff retention are suggested.

  19. Permeability of phospholipid membrane for small polar molecules determined from osmotic swelling of giant phospholipid vesicles

    CERN Document Server

    Peterlin, Primoz; Diamant, Haim; Haleva, Emir

    2012-01-01

    A method for determining permeability of phospholipid bilayer based on the osmotic swelling of micrometer-sized giant unilamellar vesicles (GUVs) is presented as an alternative to the two established techniques, dynamic light scattering on liposome suspension, and electrical measurements on planar lipid bilayers. In the described technique, an individual GUV is transferred using a micropipette from a sucrose/glucose solution into an isomolar solution containing the solute under investigation. Throughout the experiment, vesicle cross-section is monitored and recorded using a digital camera mounted on a phase-contrast microscope. Using a least-squares procedure for circle fitting, vesicle radius R is computed from the recorded images of vesicle cross-section. Two methods for determining membrane permeability from the obtained R(t) dependence are described: the first one uses the slope of R(t) for a spherical GUV, and the second one the R(t) dependence around the transition point at which a flaccid vesicle trans...

  20. Pitfalls in quantifying species turnover: the residency effect

    Directory of Open Access Journals (Sweden)

    Kevin Chase Burns

    2014-03-01

    Full Text Available The composition of ecological communities changes continuously through time and space. Understanding this turnover in species composition is a central goal in biogeography, but quantifying species turnover can be problematic. Here, I describe an underappreciated source of bias in quantifying species turnover, namely ‘the residency effect’, which occurs when the contiguous distributions of species across sampling domains are small relative to census intervals. I present the results of a simulation model that illustrates the problem theoretically and then I demonstrate the problem empirically using a long-term dataset of plant species turnover on islands. Results from both exercises indicate that empirical estimates of species turnover may be susceptible to significant observer bias, which may potentially cloud a better understanding of how the composition of ecological communities changes through time.

  1. Regulatory mechanisms of skeletal muscle protein turnover during exercise

    DEFF Research Database (Denmark)

    Rose, Adam John; Richter, Erik

    2009-01-01

    Skeletal muscle protein turnover is a relatively slow metabolic process that is altered by various physiological stimuli such as feeding/fasting and exercise. During exercise, catabolism of amino acids contributes very little to ATP turnover in working muscle. With regards to protein turnover......, there is now consistent data from tracer studies in rodents and humans showing that global protein synthesis is blunted in working skeletal muscle. Whether there is altered skeletal muscle protein breakdown during exercise remains unclear. The blunting of protein synthesis is believed to be mediated...... downstream of changes in intracellular Ca(2+) and energy turnover. In particular, a signaling cascade involving Ca(2+)-calmodulin-eEF2 kinase-eEF2 is implicated. The possible functional significance of altered protein turnover in working skeletal muscle during exercise is discussed. Further work...

  2. Effects of Silica on Serum Phospholipid,Lipid Peroxide and Morphological Characteristics of Rat Lung

    Institute of Scientific and Technical Information of China (English)

    GUOWEI-XIN; LIGUO-HUA; 等

    1995-01-01

    The effects of instilled silica have been studied on the serum-phospholipid(PL).lipid peroxide(LPO)and histopathology of rat lung up to 140 days from the first day of instillation.Silica induced relatively higher serum-PL throunghout the experiment.The level of LPO also increased appreciably.They presented positive linear correlation.The early lesion was acute alveolitis with silica particles.These lesions became silicotic nodules on the 30th day,which then were enlargen gradually and fused by fibrosis.Alveolar macrophages(AM)were activated and surface structure was damaged.These results indicate that instilled silica can induce lipid peroxidation of cell membrane and selective accumulation of lung PL.

  3. How Serious of a Problem is Staff Turnover in Substance Abuse Treatment? A Longitudinal Study of Actual Turnover1

    Science.gov (United States)

    Eby, Lillian T.; Burk, Hannah; Maher, Charleen P.

    2010-01-01

    In the substance abuse treatment field, the annual turnover rate is cited as being anywhere between 19 and 50 percent (Johnson & Roman, 2002; Gallon, Gabriel, & Knudsen, 2003; Knudsen et al., 2003; McLellan et al., 2003). However, no research to date has evaluated these claims by tracking turnover longitudinally using organizational turnover data from substance abuse treatment centers. This research presents the results of a longitudinal study designed to systematically examine actual turnover among counselors and clinical supervisors. Twenty-seven geographically dispersed treatment organizations, serving a wide range of clients in the public and private sector, provided data for the study over a two year time span (2008–2009). The annual turnover rate was 33.2% for counselors and 23.4% for clinical supervisors. For both groups the majority of turnover was voluntary (employee-initiated). Specific reasons for turnover were largely consistent across the two groups, with the most common reason being a new job or new opportunity. The findings are discussed in terms of the unique employment context of substance abuse treatment. Practical recommendations are also discussed to help stem the tide of turnover in the field of substance abuse treatment. PMID:20675097

  4. How serious of a problem is staff turnover in substance abuse treatment? A longitudinal study of actual turnover.

    Science.gov (United States)

    Eby, Lillian T; Burk, Hannah; Maher, Charleen P

    2010-10-01

    In the substance abuse treatment field, the annual turnover rate is cited as being anywhere between 19% and 50% (J.A. Johnson & P.M. Roman, 2002; S.L. Gallon, R.M. Gabriel, J.R.W. Knudsen, 2003; H.K. Knudsen, J.A. Johnson, & P.M. Roman, 2003; A.T. McLellan, D. Carise, & H.D. Kleber, 2003). However, no research to date has evaluated these claims by tracking turnover longitudinally using organizational turnover data from substance abuse treatment centers. This research presents the results of a longitudinal study designed to systematically examine actual turnover among counselors and clinical supervisors. Twenty-seven geographically dispersed treatment organizations, serving a wide range of clients in the public and private sector, provided data for the study over a 2-year time span (2008-2009). The annual turnover rate was 33.2% for counselors and 23.4% for clinical supervisors. For both groups, the majority of turnover was voluntary (employee-initiated). Specific reasons for turnover were largely consistent across the two groups, with the most common reason being a new job or new opportunity. The findings are discussed in terms of the unique employment context of substance abuse treatment. Practical recommendations are also discussed to help stem the tide of turnover in the field of substance abuse treatment. Copyright (c) 2010 Elsevier Inc. All rights reserved.

  5. Differential challenge stressor-hindrance stressor relationships with job attitudes, turnover intentions, turnover, and withdrawal behavior: a meta-analysis.

    Science.gov (United States)

    Podsakoff, Nathan P; LePine, Jeffery A; LePine, Marcie A

    2007-03-01

    In this article, a 2-dimensional work stressor framework is used to explain inconsistencies in past research with respect to stressor relationships with retention-related criteria. Results of meta-analyses of 183 independent samples indicated that whereas hindrance stressors had dysfunctional relationships with these criteria (negative relationships with job satisfaction and organizational commitment and positive relationships with turnover intentions, turnover, and withdrawal behavior), relationships with challenge stressors were generally the opposite (positive relationships with job satisfaction and organizational commitment and negative relationships with turnover intentions and turnover). Results also suggested that the differential relationships between challenge stressors and hindrance stressors and the more distal criteria (withdrawal behavior and turnover) were due, in part, to the mediating effects of job attitudes. (c) 2007 APA, all rights reserved.

  6. A model for modulation of neuronal synchronization by D4 dopamine receptor-mediated phospholipid methylation.

    Science.gov (United States)

    Kuznetsova, Anna Y; Deth, Richard C

    2008-06-01

    We describe a new molecular mechanism of dopamine-induced membrane protein modulation that can tune neuronal oscillation frequency to attention-related gamma rhythm. This mechanism is based on the unique ability of D4 dopamine receptors (D4R) to carry out phospholipid methylation (PLM) that may affect the kinetics of ion channels. We show that by deceasing the inertia of the delayed rectifier potassium channel, a transition to 40 Hz oscillations can be achieved. Decreased potassium channel inertia shortens spike duration and decreases the interspike interval via its influence on the calcium-dependent potassium current. This mechanism leads to a transition to attention-related gamma oscillations in a pyramidal cell-interneuron network. The higher frequency and better synchronization is observed with PLM affecting pyramidal neurons only, and recurrent excitation between pyramidal neurons is important for synchronization. Thus dopamine-stimulated methylation of membrane phospholipids may be an important mechanism for modulating firing activity, while impaired methylation can contribute to disorders of attention.

  7. Coupling of the fusion and budding of giant phospholipid vesicles containing macromolecules.

    Science.gov (United States)

    Terasawa, Hidetoshi; Nishimura, Kazuya; Suzuki, Hiroaki; Matsuura, Tomoaki; Yomo, Tetsuya

    2012-04-17

    Mechanisms that enabled primitive cell membranes to self-reproduce have been discussed based on the physicochemical properties of fatty acids; however, there must be a transition to modern cell membranes composed of phospholipids [Budin I, Szostak JW (2011) Proc Natl Acad Sci USA 108:5249-5254]. Thus, a growth-division mechanism of membranes that does not depend on the chemical nature of amphiphilic molecules must have existed. Here, we show that giant unilamellar vesicles composed of phospholipids can undergo the coupled process of fusion and budding transformation, which mimics cell growth and division. After gaining excess membrane by electrofusion, giant vesicles spontaneously transform into the budded shape only when they contain macromolecules (polymers) inside their aqueous core. This process is a result of the vesicle maximizing the translational entropy of the encapsulated polymers (depletion volume effect). Because the cell is a lipid membrane bag containing highly concentrated biopolymers, this coupling process that is induced by physical and nonspecific interactions may have a general importance in the self-reproduction of the early cellular compartments.

  8. Effect of vasoactive intestinal peptide on pulmonary surfactants phospholipid synthesis in lung explants

    Institute of Scientific and Technical Information of China (English)

    Lian LI; Zi-qiang LUO; Fu-wen ZHOU; Dan-dan FENG; Cha-xiang GUAN; Chang-qing ZHANG; Xiu-hong SUN

    2004-01-01

    AIM: To investigate the effect of vasoactive intestinal peptide (VIP) on pulmonary surfactants (PS) phospholipid synthesis in cultured lung explants. METHODS: Lung explants were cultured with serum-free medium, [methyl-3H]choline incorporation, total phospholipid, phosphatidylcholine, activity of choline-phosphate cytidylyltransferase (CCT) and CCTα mRNA level in lung explants were determined. RESULTS: (1) VIP (10-10-10-7 mol/L) for 16 h promoted [methyl-3H]choline incorporation in dose dependence and VIP (10-8 mol/L) for 2 h-16 h promoted [methylz3H]choline incorporation in time dependence. (2) VIP (10-8 mol/L) enhanced the contents of total phospholipidsand phosphatidylcholine in lung explants. (3) VIP (10-10-10-7 mol/L) elevated microsomal CCT activity of lung explants in dose dependence. (4) VIP (10-8 mol/L) increased expression of CCTα mRNA in lung explants and alveolar type Ⅱ cells (ATII). (5) [D-P-Cl-Phe(6)-Leu(17)]-VIP (10-6 mol/L), a VIP receptors antagonist, abolished the increase of [3H]choline incorporation, microsomal CCT activity and CCTα mRNA level induced by VIP (10-8 mol/L) in lung explants. CONCLUSION: VIP could enhance synthesis of phosphatidylcholine, the major component of pulmonary surfactants by enhancing microsomal CCT activity and CCTα mRNA level via VIP receptormediated pathway.

  9. Calcium-dependent phospholipid catabolism and arachidonic acid mobilization in cerebral minces

    Energy Technology Data Exchange (ETDEWEB)

    Damron, D.S.; Dorman, R.V. (Kent State Univ., OH (USA))

    1990-06-01

    Cerebral minces were used to investigate the role of calcium influx on trauma-induced alterations of brain lipid metabolism. Cerebral phospholipids, nonpolar lipids, and free fatty acids were radiolabeled in vivo with ({sup 3}H)arachidonic acid. Tissue incubation stimulated the time-dependent catabolism of choline and inositol glycerophospholipids, and resulted in the accumulation of ({sup 3}H)free fatty acids. These effects were attenuated in Ca{sup 2}{sup +}-free incubations, and when EGTA or verapamil were present. The inhibition of calcium influx also reduced the labeling of diglycerides, whereas ethanolamine and serine glycerophospholipids were not affected by incubation or treatments. Replacing Ca{sup 2}{sup +} with other cations also attenuated the incubation-dependent alterations in lipid metabolism. However, only cadmium was able to compete with calcium and reduce the accumulation of ({sup 3}H)free fatty acids. It appeared that about half of the observed phospholipid catabolism was dependent on Ca{sup 2}{sup +} influx and that at least 80% of the ({sup 3}H)free fatty acid accumulation required calcium.

  10. Effects of Stretching Speed on Mechanical Rupture of Phospholipid/Cholesterol Bilayers: Molecular Dynamics Simulation

    Science.gov (United States)

    Shigematsu, Taiki; Koshiyama, Kenichiro; Wada, Shigeo

    2015-01-01

    Rupture of biological cell membrane under mechanical stresses is critical for cell viability. It is triggered by local rearrangements of membrane molecules. We investigated the effects of stretching speed on mechanical rupture of phospholipid/cholesterol bilayers using unsteady molecular dynamics simulations. We focused on pore formation, the trigger of rupture, in a 40 mol% cholesterol-including bilayer. The unsteady stretching was modeled by proportional and temporal scaling of atom positions at stretching speeds from 0.025 to 30 m/s. The effects of the stretching speed on the critical areal strain, where the pore forms, is composed of two regimes. At low speeds (stretching speeds, which qualitatively agrees with available experimental data. Transient recovery of the cholesterol and phospholipid molecular orientations was evident at lower speeds, suggesting the formation of a stretch-induced interdigitated gel-like phase. However, this recovery was not confirmed at higher speeds or for the pure bilayer. The different responses of the molecular orientations may help explain the two regimes for the effect of stretching speed on pore formation. PMID:26471872

  11. Effects of Stretching Speed on Mechanical Rupture of Phospholipid/Cholesterol Bilayers: Molecular Dynamics Simulation.

    Science.gov (United States)

    Shigematsu, Taiki; Koshiyama, Kenichiro; Wada, Shigeo

    2015-10-16

    Rupture of biological cell membrane under mechanical stresses is critical for cell viability. It is triggered by local rearrangements of membrane molecules. We investigated the effects of stretching speed on mechanical rupture of phospholipid/cholesterol bilayers using unsteady molecular dynamics simulations. We focused on pore formation, the trigger of rupture, in a 40 mol% cholesterol-including bilayer. The unsteady stretching was modeled by proportional and temporal scaling of atom positions at stretching speeds from 0.025 to 30 m/s. The effects of the stretching speed on the critical areal strain, where the pore forms, is composed of two regimes. At low speeds (stretching speeds, which qualitatively agrees with available experimental data. Transient recovery of the cholesterol and phospholipid molecular orientations was evident at lower speeds, suggesting the formation of a stretch-induced interdigitated gel-like phase. However, this recovery was not confirmed at higher speeds or for the pure bilayer. The different responses of the molecular orientations may help explain the two regimes for the effect of stretching speed on pore formation.

  12. Phospholipid dysregulation contributes to ApoE4-associated cognitive deficits in Alzheimer's disease pathogenesis.

    Science.gov (United States)

    Zhu, Li; Zhong, Minghao; Elder, Gregory A; Sano, Mary; Holtzman, David M; Gandy, Sam; Cardozo, Christopher; Haroutunian, Vahram; Robakis, Nikolaos K; Cai, Dongming

    2015-09-22

    The apolipoprotein E4 (ApoE4) allele is the strongest genetic risk factor for developing sporadic Alzheimer's disease (AD). However, the mechanisms underlying the pathogenic nature of ApoE4 are not well understood. In this study, we have found that ApoE proteins are critical determinants of brain phospholipid homeostasis and that the ApoE4 isoform is dysfunctional in this process. We have found that the levels of phosphoinositol biphosphate (PIP2) are reduced in postmortem human brain tissues of ApoE4 carriers, in the brains of ApoE4 knock-in (KI) mice, and in primary neurons expressing ApoE4 alleles compared with those levels in ApoE3 counterparts. These changes are secondary to increased expression of a PIP2-degrading enzyme, the phosphoinositol phosphatase synaptojanin 1 (synj1), in ApoE4 carriers. Genetic reduction of synj1 in ApoE4 KI mouse models restores PIP2 levels and, more important, rescues AD-related cognitive deficits in these mice. Further studies indicate that ApoE4 behaves similar to ApoE null conditions, which fails to degrade synj1 mRNA efficiently, unlike ApoE3 does. These data suggest a loss of function of ApoE4 genotype. Together, our data uncover a previously unidentified mechanism that links ApoE4-induced phospholipid changes to the pathogenic nature of ApoE4 in AD.

  13. The effect of acute exercise on collagen turnover in human tendons

    DEFF Research Database (Denmark)

    Mørch, Lina Steinrud; Pingel, Jessica; Boesen, Mikael;

    2013-01-01

    Mechanical loading of human tendon stimulates collagen synthesis, but the relationship between acute loading responses and training status of the tendon is not clear. We tested the effect of prolonged load deprivation on the acute loading-induced collagen turnover in human tendons, by applying...... and compared to values obtained by 72-h post-exercise. Power Doppler was used to monitor alterations in intratendinous blood flow velocity of the Achilles tendon and MRI used to quantitate changes in tendon cross-section area. Acute loading resulted in an increased collagen synthesis 72 h after the run in both...... the contra-lateral leg was used habitually. Following the procedure both Achilles tendons and calf muscles were loaded with the same absolute load during a 1-h treadmill run. Tissue collagen turnover was measured by microdialysis performed post-immobilization but pre-exercise around both Achilles tendons...

  14. A review on phospholipids and their main applications in drug delivery systems

    Directory of Open Access Journals (Sweden)

    Jing Li

    2015-04-01

    Full Text Available Phospholipids have the characteristics of excellent biocompatibility and a especial amphiphilicity. These unique properties make phospholipids most appropriate to be employed as important pharmaceutical excipients and they have a very wide range of applications in drug delivery systems. The aim of this review is to summarize phospholipids and some of their related applications in drug delivery systems, and highlight the relationship between the properties and applications, and the effect of the species of phospholipids on the efficiency of drug delivery. We refer to some relevant literatures, starting from the structures, main sources and properties of phospholipids to introduce their applications in drug delivery systems. The present article focuses on introducing five types of carriers based on phospholipids, including liposomes, intravenous lipid emulsions, micelles, drug-phospholipids complexes and cochleates.

  15. Staff turnover in statewide implementation of ACT: relationship with ACT fidelity and other team characteristics.

    Science.gov (United States)

    Rollins, Angela L; Salyers, Michelle P; Tsai, Jack; Lydick, Jennifer M

    2010-09-01

    Staff turnover on assertive community treatment (ACT) teams is a poorly understood phenomenon. This study examined annual turnover and fidelity data collected in a statewide implementation of ACT over a 5-year period. Mean annual staff turnover across all observations was 30.0%. Turnover was negatively correlated with overall fidelity at Year 1 and 3. The team approach fidelity item was negatively correlated with staff turnover at Year 3. For 13 teams with 3 years of follow-up data, turnover rates did not change over time. Most ACT staff turnover rates were comparable or better than other turnover rates reported in the mental health and substance abuse literature.

  16. Organizational culture, job satisfaction, and clinician turnover in primary care.

    Science.gov (United States)

    Hall, Charles B; Brazil, Kevin; Wakefield, Dorothy; Lerer, Trudy; Tennen, Howard

    2010-04-01

    The purpose of this study is to examine how organizational culture and job satisfaction affect clinician turnover in primary care pediatric practices. One hundred thirty clinicians from 36 primary care pediatric practices completed the Primary Care Organizational Questionnaire (PCOQ), which evaluates interactions among members of the practice and job-related attributes measuring 8 organizational factors, along with a separate 3-item instrument measuring job satisfaction. Random effects logistic models were used to assess the associations between job satisfaction, the organizational factors from the PCOQ, and clinician turnover over the subsequent year. All 8 measured organizational factors from the PCOQ, particularly perceived effectiveness, were associated with job satisfaction. Five of the 8 organizational factors were also associated with clinician turnover. The effects of the organizational factors on turnover were substantially reduced in a model that included job satisfaction; only 1 organizational factor, communication between clinicians and nonclinicians, remained significant (P = .05). This suggests that organizational culture affects subsequent clinician turnover primarily through its effect on job satisfaction. Organizational culture, in particular perceived effectiveness and communication, affects job satisfaction, which in turn affects clinician turnover in primary care pediatric practices. Strategies to improve job satisfaction through changes in organizational culture could potentially reduce clinician turnover.

  17. Turnover of sex chromosomes induced by sexual conflict

    NARCIS (Netherlands)

    van Doorn, G. S.; Kirkpatrick, Mark

    2007-01-01

    Sex-determination genes are among the most fluid features of the genome in many groups of animals(1,2). In some taxa the master sex-determining gene moves frequently between chromosomes, whereas in other taxa different genes have been recruited to determine the sex of the zygotes. There is a well

  18. Increased hypothalamic serotonin turnover in inflammation-induced anorexia

    OpenAIRE

    Dwarkasing, J.T.; Witkamp, R F; Boekschoten, M.V.; Laak, ter, H.J.; Heins, M.S.; Norren, van, K.

    2016-01-01

    Background Anorexia can occur as a serious complication of disease. Increasing evidence suggests that inflammation plays a major role, along with a hypothalamic dysregulation characterized by locally elevated serotonin levels. The present study was undertaken to further explore the connections between peripheral inflammation, anorexia and hypothalamic serotonin metabolism and signaling pathways. First, we investigated the response of two hypothalamic neuronal cell lines to TNFα, IL-6 and LPS....

  19. Increased hypothalamic serotonin turnover in inflammation-induced anorexia

    NARCIS (Netherlands)

    Dwarkasing, J.T.; Witkamp, R.F.; Boekschoten, M.V.; Laak, ter M.C.; Heins, M.S.; Norren, van K.

    2016-01-01

    Background: Anorexia can occur as a serious complication of disease. Increasing evidence suggests that inflammation plays a major role, along with a hypothalamic dysregulation characterized by locally elevated serotonin levels. The present study was undertaken to further explore the connections b

  20. Turnover of sex chromosomes induced by sexual conflict

    NARCIS (Netherlands)

    van Doorn, G. S.; Kirkpatrick, Mark

    2007-01-01

    Sex-determination genes are among the most fluid features of the genome in many groups of animals(1,2). In some taxa the master sex-determining gene moves frequently between chromosomes, whereas in other taxa different genes have been recruited to determine the sex of the zygotes. There is a well de

  1. The effect of phospholipid transfer protein on cigarette smoke extract induced epithelial-mesenchymal transition of rat alveolar type Ⅱ cells%磷脂转运蛋白在烟草诱导RLE-6TN细胞株发生上皮间质转化中的作用

    Institute of Scientific and Technical Information of China (English)

    巫凤苹; 陈亚娟; 余秀英; 廖科; 李丹丹; 陈虹

    2016-01-01

    Objective To investigate the effect of phospholipid transfer protein(PLTP) on cigarette smoke extract(CSE) induced epithelial-mesenchymal transition(EMT) in rat alveolar Type Ⅱ cells (RLE-6TN).Methods CSE of different concentrations (0%,0.25%,0.5% and 1%) was co-cultured for 2 or 3days with RLE-6TN,either pre-treated or not pre-treated with siRNA-PLTP for 6 h.Expression levels of E-cadherin mRNA and Vimentin mRNA were examined by RT-PCR,while expression levels of PLTP,E-cadherin,N-cadherin and Vimentin were examined by Western blot.Results Our results showed that the expression of E-cadherin mRNA decreased in CSE-treated groups:1.01 ± 0.05,0.74 ± 0.05,0.65 ± 0.03,0.30 ±0.08 respectively at different concentrations of CSE (0 %,0.25%,0.5 %,and 1.0%);while the level of Vimentin mRNA increased significantly in 1% CSE treated cells (1.88 ± O.49),compared with control cells (1.01 ±0.20).Treatment with CSE at different concentrations (0%,0.25%,0.5% and 1%) showed that the protein levels of PLTP were 0.42 ± 0.02,0.89 ± 0.25,1.08 ± 0.18,1.61 ± 0.06 respectively;those of E-cadherin were 1.61 ± 0.04,1.08 ± 0.10,0.62 ± 0.08,0.68 ± 0.17,respectively;those of N-cadherin were 0.60 ± 0.14,0.57 ± 0.26,0.88 ± 0.30,1.94 ± 0.54,respectively;and those of Vimentin were 0.61 ± 0.05,0.98 ± 0.16,1.07 ± 0.14,1.34 ± 0.19,respectively;all P < 0.05 when the 1% CSE group was compared with the control group.EMT induced by CSE was significantly inhibited by siRNA-PLTP.Conclusion PLTP may be involved in CSE induced EMT of rat alveolar cells.%目的 探讨磷脂转运蛋白(PLTP)在烟草提取物(CSE)诱导大鼠Ⅱ型肺泡上皮细胞株RLE-6TN发生上皮间质转化(EMT)中的作用.方法 体外培养RLE-6TN细胞株24 h,分为4组,每组3孔,分别加入0%、0.25%、0.5%和1% CSE培养2d,检测E-钙黏蛋白和波形蛋白mRNA表达以及细胞和CSE共培养3d检测PLTP、EMT相关蛋白(E-钙黏蛋白、N-钙黏蛋白和波形

  2. Inhibition of biliary cholesterol and phospholipid secretion by cefmetazole. The role of vesicular transport and of canalicular events.

    Science.gov (United States)

    Cava, F; Gonzalez, J; Gonzalez-Buitrago, J M; Muriel, C; Jimenez, R

    1991-01-01

    A number of organic anions selectively inhibit the biliary secretion of cholesterol and phospholipids without affecting bile acid secretion. We studied the effect of cefmetazole, a third-generation cephalosporin, on biliary lipid secretion in the rat. Injection of cefmetazole at a dose of 200 mumol/kg body wt. induced a choleretic effect and a significant decrease in the biliary output of cholesterol and phospholipid, without changes in bile acid secretion. The decrease was more marked for cholesterol than for phospholipid secretion, with a significant decrease in their molar ratio in bile. The effects were apparently unrelated to an inhibition of intracellular vesicular transport because, after injection of horseradish peroxidase, both the time course and total amount secreted of the protein did not significantly differ between control animals and those receiving cefmetazole. The secretory rate of the lysosomal marker acid phosphatase was not affected by cefmetazole administration. Biliary outputs of the plasma-membrane enzymes alkaline phosphatase and gamma-glutamyltransferase were significantly decreased by the antibiotic. These results point to an effect of cefmetazole at the level of the canalicular membrane. PMID:1674860

  3. The curvilinear effect of work engagement on employees' turnover intentions.

    Science.gov (United States)

    Caesens, Gaëtane; Stinglhamber, Florence; Marmier, Virginie

    2016-04-01

    Numerous studies have shown the positive consequences of work engagement for both organisations and employees experiencing it. For instance, research has demonstrated that work-engaged employees have lower levels of turnover intentions than non-engaged employees. However, in this research, we examined whether there is a dark side of work engagement. More precisely, we investigated whether the relationship between work engagement and employees' turnover intentions might be non-linear. Based on two different samples, our results indicated that the relationship between work engagement and employees' turnover intentions is curvilinear. The theoretical and practical implications of these results are discussed.

  4. Turnover Rate of Popularity Charts in Neutral Models

    CERN Document Server

    Evans, T S

    2011-01-01

    It has been shown recently that in many different cultural phenomena the turnover rate on the most popular artefacts in a population exhibit some regularities. A very simple expression for this turnover rate has been proposed by Bentley et al. and its validity in two simple models for copying and innovation is investigated in this paper. It is found that Bentley's formula is an approximation of the real behaviour of the turnover rate in the Wright-Fisher model, while it is not valid in the Moran model.

  5. Employee turnover and productivity among small business entities in Nigeria

    Directory of Open Access Journals (Sweden)

    John N. N. Ugoani

    2016-12-01

    Full Text Available This study was designed to evaluate the problems of employee turnover on productivity among small business entities in Nigeria, and recommend remedial actions. Employee turnover is the separation of employees from employers and replacement with other employees. Productive manpower is a critical element for the economic survival of any small business entity. The survey research design was used for the study. The sample comprised of 320 respondents. Data generated were analyzed by using descriptive, and Z-test statistical techniques. It was found that employee turnover adversely affects productivity in small business entities.

  6. Endocytic turnover of Rab8 controls cell polarization

    Science.gov (United States)

    Vidal-Quadras, Maite; Holst, Mikkel R.; Larsson, Elin; Hachimi, Mariam; Yau, Wai-Lok; Peränen, Johan; Martín-Belmonte, Fernando

    2017-01-01

    ABSTRACT Adaptation of cell shape and polarization through the formation and retraction of cellular protrusions requires balancing of endocytosis and exocytosis combined with fine-tuning of the local activity of small GTPases like Rab8. Here, we show that endocytic turnover of the plasma membrane at protrusions is directly coupled to surface removal and inactivation of Rab8. Removal is induced by reduced membrane tension and mediated by the GTPase regulator associated with focal adhesion kinase-1 (GRAF1, also known as ARHGAP26), a regulator of clathrin-independent endocytosis. GRAF1-depleted cells were deficient in multi-directional spreading and displayed elevated levels of GTP-loaded Rab8, which was accumulated at the tips of static protrusions. Furthermore, GRAF1 depletion impaired lumen formation and spindle orientation in a 3D cell culture system, indicating that GRAF1 activity regulates polarity establishment. Our data suggest that GRAF1-mediated removal of Rab8 from the cell surface restricts its activity during protrusion formation, thereby facilitating dynamic adjustment of the polarity axis. PMID:28137756

  7. Hsp90 inhibition decreases mitochondrial protein turnover.

    Directory of Open Access Journals (Sweden)

    Daciana H Margineantu

    Full Text Available BACKGROUND: Cells treated with hsp90 inhibitors exhibit pleiotropic changes, including an expansion of the mitochondrial compartment, accompanied by mitochondrial fragmentation and condensed mitochondrial morphology, with ultimate compromise of mitochondrial integrity and apoptosis. FINDINGS: We identified several mitochondrial oxidative phosphorylation complex subunits, including several encoded by mtDNA, that are upregulated by hsp90 inhibitors, without corresponding changes in mRNA abundance. Post-transcriptional accumulation of mitochondrial proteins observed with hsp90 inhibitors is also seen in cells treated with proteasome inhibitors. Detailed studies of the OSCP subunit of mitochondrial F1F0-ATPase revealed the presence of mono- and polyubiquitinated OSCP in mitochondrial fractions. We demonstrate that processed OSCP undergoes retrotranslocation to a trypsin-sensitive form associated with the outer mitochondrial membrane. Inhibition of proteasome or hsp90 function results in accumulation of both correctly targeted and retrotranslocated mitochondrial OSCP. CONCLUSIONS: Cytosolic turnover of mitochondrial proteins demonstrates a novel connection between mitochondrial and cytosolic compartments through the ubiquitin-proteasome system. Analogous to defective protein folding in the endoplasmic reticulum, a mitochondrial unfolded protein response may play a role in the apoptotic effects of hsp90 and proteasome inhibitors.

  8. Osteocalcin: an emerging biomarker for bone turnover

    Directory of Open Access Journals (Sweden)

    Brijesh Rathore

    2016-09-01

    Full Text Available Osteocalcin (OC is produced by osteoblasts during bone formation. OC is excreted into urine by glomerular filtration and can be found as fragments in urine. The presence of three vitamin K-dependent and #947;-carboxyglutamic acid residues is critical for osteocalcin's structure, which appears to regulate the maturation of bone mineral. Recent bone biology research have highlighted the importance of bone not only as a structural scaffold to support the human body, but also as a regulator of a metabolic processes that are independent of mineral metabolism. Circulating osteocalcin is present either as carboxylated or as undercarboxylated forms. Increased serum level of osteocalcin is linked with increased bone mineral density. The importance of the bone and ndash;kidney relation in physiologic regulation of mineral ion has also been extensively studied and documented. Several workers have uncovered the role of insulin as an additional factor involved in the skeletal remodelling process. Evidences are available which shows that osteoblastic insulin signalling is important for glucose metabolism. The measurement of OC in urine samples could be used as an index of bone turnover in monitoring bone metabolism. In this review, we have tried to explain different roles of OC, however further studies are required to elucidate the metabolic and hormonal role of OC in human body. [Int J Res Med Sci 2016; 4(9.000: 3670-3674

  9. Effect of engineered TiO2 and ZnO nanoparticles on erythrocytes, platelet-rich plasma and giant unilamelar phospholipid vesicles

    Directory of Open Access Journals (Sweden)

    Šimundić Metka

    2013-01-01

    Full Text Available Abstract Background Massive industrial production of engineered nanoparticles poses questions about health risks to living beings. In order to understand the underlying mechanisms, we studied the effects of TiO2 and ZnO agglomerated engineered nanoparticles (EPs on erythrocytes, platelet-rich plasma and on suspensions of giant unilamelar phospholipid vesicles. Results Washed erythrocytes, platelet-rich plasma and suspensions of giant unilamelar phospholipid vesicles were incubated with samples of EPs. These samples were observed by different microscopic techniques. We found that TiO2 and ZnO EPs adhered to the membrane of washed human and canine erythrocytes. TiO2 and ZnO EPs induced coalescence of human erythrocytes. Addition of TiO2 and ZnO EPs to platelet-rich plasma caused activation of human platelets after 24 hours and 3 hours, respectively, while in canine erythrocytes, activation of platelets due to ZnO EPs occurred already after 1 hour. To assess the effect of EPs on a representative sample of giant unilamelar phospholipid vesicles, analysis of the recorded populations was improved by applying the principles of statistical physics. TiO2 EPs did not induce any notable effect on giant unilamelar phospholipid vesicles within 50 minutes of incubation, while ZnO EPs induced a decrease in the number of giant unilamelar phospholipid vesicles that was statistically significant (p  Conclusions These results indicate that TiO2 and ZnO EPs cause erythrocyte aggregation and could be potentially prothrombogenic, while ZnO could also cause membrane rupture.

  10. Interactions Mode of Amphoteric Molecules with Ordered Phospholipid Membrane

    Institute of Scientific and Technical Information of China (English)

    SUNJin; CHENGGang; HEZhong-gui; WANGshu-jun; CHENJi-min

    2003-01-01

    Aim:To explore interaction mode between amphoteric molecules with the ordered phospholipid membrane.Methods:Membrane interactions were determined by immobilized artificial membrane(IAM) chromatography and solutes hydroph9obicity was measured by n-octanol/buffer system.Results:The ampholytes,similar to bases,generally exhibited higher membrane affinity than expected from their hydrophobicity,resulting from the attractive polar interaction with phospholipid membrane.Furthermore,the strength of additional polar interaction with membrane(Δlg kLAM) was then calculat ed.The Δlg KIAMvalues were far greater for bases and ampholytes ranging from 0.50-1.39,than those for acids and neutrals with the scope from-0.55-0.44.Conclusion :Considering the microspecies distribution of amphoteric molecules,it was assumed that not only neutral and positive but also zwitterionic microspecies are capable of partitioning into ordered amphoteric lipid membrane with complementarily conformational and energetically favorable interactions.

  11. Training affects muscle phospholipid fatty acid composition in humans

    DEFF Research Database (Denmark)

    Helge, Jørn Wulff; Wu, B J; Willer, Mette

    2001-01-01

    Training improves insulin sensitivity, which in turn may affect performance by modulation of fuel availability. Insulin action, in turn, has been linked to specific patterns of muscle structural lipids in skeletal muscle. This study investigated whether regular exercise training exerts an effect...... on the muscle membrane phospholipid fatty acid composition in humans. Seven male subjects performed endurance training of the knee extensors of one leg for 4 wk. The other leg served as a control. Before, after 4 days, and after 4 wk, muscle biopsies were obtained from the vastus lateralis. After 4 wk......, the phospholipid fatty acid contents of oleic acid 18:1(n-9) and docosahexaenoic acid 22:6(n-3) were significantly higher in the trained (10.9 +/- 0.5% and 3.2 +/- 0.4% of total fatty acids, respectively) than the untrained leg (8.8 +/- 0.5% and 2.6 +/- 0.4%, P

  12. Study on Phospholipid Composition of Erythrocyte Membrane in Hypophosphatemic Cows

    Institute of Scientific and Technical Information of China (English)

    SHI Fa-qing; XUAN Da-wei; XU Shi-Wen; WANG Zhen-yong

    2002-01-01

    The phospholipid constituents of the erythrocyte membrane of cows in hypophosophorus were detected with the field cases and the group comparison. The cows were divided into three groups: the hemoglobinuria group (HN), the hypophosphatemia group (HP) and the control group (CK). The content of the phospholipid constituent in HN and HP obviously changed: phosphatidylethaanolamine (PE) content in HN was significantly lower than that in HP and CK; but sphingomyline (SM) and phosphatidycholine (PC)+ phosphatidylserine (PS) content in HN were significantly higher than that in the two other groups; in comparison between HP and CK, PC + PS content was lower and SM content was higher in HP; significant positive correlation and negative correlation were observed between serum phosphorus and PE content, serum phosphorus and SM content respectively.

  13. Interaction of SynaptotagminⅠ with Phospholipid Membrane: A Monolayer Study

    Institute of Scientific and Technical Information of China (English)

    贺雨虹; 隋森芳

    2002-01-01

    Synaptotagmin Ⅰ(sytⅠ) is an abundant integral membrane protein of the synaptic vesicle and the C2A domain is an important functional domain in the cytoplasmic part of sytⅠ. C2A prefers to interact with plasmic membranes of neuron cells in vivo and such interaction is closely related to the sytⅠ physiological function as a Ca2+ sensor in the Ca2+-regulated neurotransmitter release. However, the interaction nature between C2A and phospholipids is not well understood. Monolayers at an air/water interface were used to study the interaction between C2A and a phospholipid membrane. The results show that C2A preferentially inserts into the negatively charged phosphatidylserine monolayer and Ca2+ ions are required for the interaction. Electrostatic force is mostly responsible for the insertion of C2A into dipalmitoyl phosphatidylserine monolayers.

  14. Elliptical structure of phospholipid bilayer nanodiscs encapsulated by scaffold proteins

    DEFF Research Database (Denmark)

    Skar-Gislinge, Nicholas; Simonsen, Jens Bæk; Mortensen, Kell

    2010-01-01

    -angle neutron scattering in combination with variable-temperature studies of synchrotron small-angle X-ray scattering on nanodiscs in solution, we show that the fundamental nanodisc unit, consisting of a lipid bilayer surrounded by amphiphilic scaffold proteins, possesses intrinsically an elliptical shape....... The temperature dependence of the curvature of the nanodiscs prepared with two different phospholipid types (DLPC and POPC) shows that it is the scaffold protein that determines the overall elliptical shape and that the nanodiscs become more circular with increasing temperature. Our data also show...... that the hydrophobic bilayer thickness is, to a large extent, dictated by the scaffolding protein and adjusted to minimize the hydrophobic mismatch between protein and phospholipid. Our conclusions result from a new comprehensive and molecular-based model of the nanodisc structure and the use of this to analyze...

  15. A Novel High Mechanical Property PLGA Composite Matrix Loaded with Nanodiamond-Phospholipid Compound for Bone Tissue Engineering.

    Science.gov (United States)

    Zhang, Fan; Song, Qingxin; Huang, Xuan; Li, Fengning; Wang, Kun; Tang, Yixing; Hou, Canglong; Shen, Hongxing

    2016-01-20

    A potential bone tissue engineering material was produced from a biodegradable polymer, poly(lactic-co-glycolic acid) (PLGA), loaded with nanodiamond phospholipid compound (NDPC) via physical mixing. On the basis of hydrophobic effects and physical absorption, we modified the original hydrophilic surface of the nanodiamond (NDs) with phospholipids to be amphipathic, forming a typical core-shell structure. The ND-phospholipid weight ratio was optimized to generate sample NDPC50 (i.e., ND-phospholipid weight ratio of 100:50), and NDPC50 was able to be dispersed in a PLGA matrix at up to 20 wt %. Compared to a pure PLGA matrix, the introduction of 10 wt % of NDPC (i.e., sample NDPC50-PF10) resulted in a significant improvement in the material's mechanical and surface properties, including a decrease in the water contact angle from 80 to 55°, an approximately 100% increase in the Young's modulus, and an approximate 550% increase in hardness, thus closely resembling that of human cortical bone. As a novel matrix supporting human osteoblast (hFOB1.19) growth, NDPC50-PFs with different amounts of NDPC50 demonstrated no negative effects on cell proliferation and osteogenic differentiation. Furthermore, we focused on the behaviors of NDPC-PFs implanted into mice for 8 weeks and found that NDPC-PFs induced acceptable immune response and can reduce the rapid biodegradation of PLGA matrix. Our results represent the first in vivo research on ND (or NDPC) as nanofillers in a polymer matrix for bone tissue engineering. The high mechanical properties, good in vitro and in vivo biocompatibility, and increased mineralization capability suggest that biodegradable PLGA composite matrices loaded with NDPC may potentially be useful for a variety of biomedical applications, especially bone tissue engineering.

  16. Yeast PAH1-encoded phosphatidate phosphatase controls the expression of CHO1-encoded phosphatidylserine synthase for membrane phospholipid synthesis.

    Science.gov (United States)

    Han, Gil-Soo; Carman, George M

    2017-08-11

    The PAH1-encoded phosphatidate phosphatase (PAP), which catalyzes the committed step for the synthesis of triacylglycerol in Saccharomyces cerevisiae, exerts a negative regulatory effect on the level of phosphatidate used for the de novo synthesis of membrane phospholipids. This raises the question whether PAP thereby affects the expression and activity of enzymes involved in phospholipid synthesis. Here, we examined the PAP-mediated regulation of CHO1-encoded phosphatidylserine synthase (PSS), which catalyzes the committed step for the synthesis of major phospholipids via the CDP-diacylglycerol pathway. The lack of PAP in the pah1Δ mutant highly elevated PSS activity, exhibiting a growth-dependent up-regulation from the exponential to the stationary phase of growth. Immunoblot analysis showed that the elevation of PSS activity results from an increase in the level of the enzyme encoded by CHO1 Truncation analysis and site-directed mutagenesis of the CHO1 promoter indicated that Cho1 expression in the pah1Δ mutant is induced through the inositol-sensitive upstream activation sequence (UASINO), a cis-acting element for the phosphatidate-controlled Henry (Ino2-Ino4/Opi1) regulatory circuit. The abrogation of Cho1 induction and PSS activity by a CHO1 UASINO mutation suppressed pah1Δ effects on lipid synthesis, nuclear/endoplasmic reticulum membrane morphology, and lipid droplet formation, but not on growth at elevated temperature. Loss of the DGK1-encoded diacylglycerol kinase, which converts diacylglycerol to phosphatidate, partially suppressed the pah1Δ-mediated induction of Cho1 and PSS activity. Collectively, these data showed that PAP activity controls the expression of PSS for membrane phospholipid synthesis. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  17. Equilibrium insertion of nanoscale objects into phospholipid bilayers

    CERN Document Server

    Pogodin, Sergey

    2011-01-01

    Certain membrane proteins, peptides, nanoparticles and nanotubes have rigid structure and fixed shape. They are often viewed as spheres and cylinders with certain surface properties. Single Chain Mean Field theory is used to model the equilibrium insertion of nanoscale spheres and rods into the phospholipid bilayer. The equilibrium structures and the resulting free energies of the nano-objects in the bilayer allow to distinguish different orientations in the bilayer and estimate the energy barrier of insertion.

  18. Differential intrahepatic phospholipid zonation in simple steatosis and nonalcoholic steatohepatitis.

    Directory of Open Access Journals (Sweden)

    Julia Wattacheril

    Full Text Available Nonalcoholic fatty liver disease (NAFLD occurs frequently in a setting of obesity, dyslipidemia and insulin resistance, but the etiology of the disease, particularly the events favoring progression to nonalcoholic steatohepatitis (NASH as opposed to simple steatosis (SS, are not fully understood. Based on known zonation patterns in protein, glucose and lipid metabolism, coupled with evidence that phosphatidylcholine may play a role in NASH pathogenesis, we hypothesized that phospholipid zonation exists in liver and that specific phospholipid abundance and distribution may be associated with histologic disease. A survey of normal hepatic protein expression profiles in the Human Protein Atlas revealed pronounced zonation of enzymes involved in lipid utilization and storage, particularly those facilitating phosphatidylcholine (PC metabolism. Immunohistochemistry of obese normal, SS and NASH liver specimens with anti-phosphatidylethanomine N-methyltransferase (PEMT antibodies showed a progressive decrease in the zonal distribution of this PC biosynthetic enzyme. Phospholipid quantitation by liquid chromatography mass spectrometry (LC-MS in hepatic extracts of Class III obese patients with increasing NAFLD severity revealed that most PC species with 32, 34 and 36 carbons as well as total PC abundance was decreased with SS and NASH. Matrix assisted laser desorption ionization-imaging mass spectrometry (MALDI-IMS imaging revealed strong zonal distributions for 32, 34 and 36 carbon PCs in controls (minimal histologic findings and SS that was lost in NASH specimens. Specific lipid species such as PC 34:1 and PC 36:2 best illustrated this phenomenon. These findings suggest that phospholipid zonation may be associated with the presence of an intrahepatic proinflammatory phenotype and thus have broad implications in the etiopathogenesis of NASH.

  19. Effect of dipolar-angle on phospholipid assembly

    CERN Document Server

    Paul, Tanay

    2016-01-01

    We report the effect of lipid head-group dipole orientation on phase behaviour of phospholipid assembly. The work explains molecular-scale mechanism of ion-lipid, anesthetic-lipid interactions where reorientation of dipoles play important role in membrane potential modification. Molecular Dynamics simulations are performed to analyse structure-property relationship and dynamical behaviour of lipid biomembranes considering coarse-grained model interactions.

  20. Nonenzymatic biomimetic remodeling of phospholipids in synthetic liposomes.

    Science.gov (United States)

    Brea, Roberto J; Rudd, Andrew K; Devaraj, Neal K

    2016-08-02

    Cell membranes have a vast repertoire of phospholipid species whose structures can be dynamically modified by enzymatic remodeling of acyl chains and polar head groups. Lipid remodeling plays important roles in membrane biology and dysregulation can lead to disease. Although there have been tremendous advances in creating artificial membranes to model the properties of native membranes, a major obstacle has been developing straightforward methods to mimic lipid membrane remodeling. Stable liposomes are typically kinetically trapped and are not prone to exchanging diacylphospholipids. Here, we show that reversible chemoselective reactions can be harnessed to achieve nonenzymatic spontaneous remodeling of phospholipids in synthetic membranes. Our approach relies on transthioesterification/acyl shift reactions that occur spontaneously and reversibly between tertiary amides and thioesters. We demonstrate exchange and remodeling of both lipid acyl chains and head groups. Using our synthetic model system we demonstrate the ability of spontaneous phospholipid remodeling to trigger changes in vesicle spatial organization, composition, and morphology as well as recruit proteins that can affect vesicle curvature. Membranes capable of chemically exchanging lipid fragments could be used to help further understand the specific roles of lipid structure remodeling in biological membranes.

  1. The local phospholipid environment modulates the activation of blood clotting.

    Science.gov (United States)

    Shaw, Andrew W; Pureza, Vincent S; Sligar, Stephen G; Morrissey, James H

    2007-03-02

    Examples abound of membrane-bound enzymes for which the local membrane environment plays an important role, including the ectoenzyme that triggers blood clotting, the plasma serine protease, factor VIIa, bound to the integral membrane protein, tissue factor. The activity of this enzyme complex is markedly influenced by lipid bilayer composition and further by tissue factor partitioning into membrane microdomains on some cell surfaces. Unfortunately, little is known about how membrane microdomain composition controls factor VIIa-tissue factor activity, as reactions catalyzed by membrane-tethered enzymes are typically studied under conditions in which the experimenter cannot control the composition of the membrane in the immediate vicinity of the enzyme. To overcome this problem, we used a nanoscale approach that afforded complete control over the membrane environment surrounding tissue factor by assembling the factor VIIa.tissue factor complex on stable bilayers containing 67 +/- 1 phospholipid molecules/leaflet (Nanodiscs). We investigated how local changes in phospholipid bilayer composition modulate the activity of the factor VIIa.tissue factor complex. We also addressed whether this enzyme requires a pool of membrane-bound protein substrate (factor X) for efficient catalysis, or alternatively if it could efficiently activate factor X, which binds directly to the membrane nanodomain adjacent to tissue factor. We have shown that full proteolytic activity of the factor VIIa.tissue factor complex requires extremely high local concentrations of anionic phospholipids and further that a large pool of membrane-bound factor X is not required to support sustained catalysis.

  2. The cation content of phospholipides from swine erythrocytes.

    Science.gov (United States)

    KIRSCHNER, L B

    1958-11-20

    Phospholipides from swine erythrocytes were isolated and separated into four reproducible fractions. One of the fractions seems to be pure phosphatidylserine. The others are almost certainly not single compounds, although the analytical data indicate that they represent mixtures considerably simpler than the parent mixture extracted from the cells. All four fractions contained Na(+) and K(+), but very little Ca(2+). Sodium was the predominant cation in two of the fractions under all conditions although the major intracellular cation was potassium. In the other two fractions the ratio Na/K varied with the extraction procedure largely because the quantity of K(+) seemed to depend on the solvent system used. There appear to be reasons to believe that the entire system of phospholipides binds Na(+) preferentially. In addition, it was observed that the quantity of Na(+) found in the lipide extracts varied when the extrusion of Na(+) from the cells was made to vary. Both of these observations are consistent with the possibility that the phospholipides play some part in the extrusion of Na(+) from these cells.

  3. Phospholipid and Respiratory Quinone Analyses From Extreme Environments

    Science.gov (United States)

    Pfiffner, S. M.

    2008-12-01

    Extreme environments on Earth have been chosen as surrogate sites to test methods and strategies for the deployment of space craft in the search for extraterrestrial life. Surrogate sites for many of the NASA astrobiology institutes include the South African gold mines, Canadian subpermafrost, Atacama Desert, and acid rock drainage. Soils, sediments, rock cores, fracture waters, biofilms, and service and drill waters represent the types of samples collected from these sites. These samples were analyzed by gas chromatography mass spectrometry for phospholipid fatty acid methyl esters and by high performance liquid chromatography atmospheric pressure chemical ionization tandem mass spectrometry for respiratory quinones. Phospholipid analyses provided estimates of biomass, community composition, and compositional changes related to nutritional limitations or exposure to toxic conditions. Similar to phospholipid analyses, respiratory quinone analyses afforded identification of certain types of microorganisms in the community based on respiration and offered clues to in situ redox conditions. Depending on the number of samples analyzed, selected multivariate statistical methods were applied to relate membrane lipid results with site biogeochemical parameters. Successful detection of life signatures and refinement of methodologies at surrogate sites on Earth will be critical for the recognition of extraterrestrial life. At this time, membrane lipid analyses provide useful information not easily obtained by other molecular techniques.

  4. The micromethod for determination of cholesterol, cholesteryl esters and phospholipids

    Directory of Open Access Journals (Sweden)

    Okabe,Akinobu

    1974-12-01

    Full Text Available We examined the method for determining microquantities of lipids, including cholesterol, cholesteryl esters and phospholipids. A standard colorimetric procedure of cholesteryl esters was modified to accommodate a quantitative thin-layer chromatography. This method involved the following steps. (1 Separation of lipids by a thin-layer chromatography: Lipids were applied to Silica gel G plates. Plates were developed with petroleum ether-diethyl etheracetic acid (82: 18: 2, vIvIv. (2 Elution of cholesterol and its esters from scraped silica gel: After scraping the silica gel with adhered cholesterol and its esters, they were eluted with chloroform-methanol (4: 1, v,tv. In the case of phspholipids, the silica gel was calcified. (3 Colorimetric determination of the lipids: Cholesterol and its esters eluted from the silica gel were determined by the method of ZAK with ROSENTHAL'S color reagent directly and after saponification, respectively. Phospholipids were calculated from the phosphorous content determined by the method of KATES. On the basis of examination of recovery and analyses of lipids extracted from tissue, it was concluded that this method permitted a reliable estimation of microquantities of cholesterol, its esters and phospholipids from small amounts of biological materials.

  5. Antioxidant effect of lutein towards phospholipid hydroperoxidation in human erythrocytes.

    Science.gov (United States)

    Nakagawa, Kiyotaka; Kiko, Takehiro; Hatade, Keijiro; Sookwong, Phumon; Arai, Hiroyuki; Miyazawa, Teruo

    2009-11-01

    Peroxidised phospholipid-mediated cytotoxity is involved in the pathophysiology of many diseases; for example, phospholipid hydroperoxides (PLOOH) are abnormally increased in erythrocytes of dementia patients. Dietary carotenoids (especially xanthophylls, polar carotenoids such as lutein) have gained attention as potent inhibitors against erythrocyte phospholipid hydroperoxidation, thereby making them plausible candidates for preventing diseases (i.e. dementia). To evaluate these points, we investigated whether orally administered lutein is distributed to human erythrocytes, and inhibits erythrocyte PLOOH formation. Six healthy subjects took one capsule of food-grade lutein (9.67 mg lutein per capsule) once per d for 4 weeks. Before and during the supplementation period, carotenoids and PLOOH in erythrocytes and plasma were determined by our developed HPLC technique. The administered lutein was incorporated into human erythrocytes, and erythrocyte PLOOH level decreased after the ingestion for 2 and 4 weeks. The antioxidative effect of lutein was confirmed on erythrocyte membranes, but not in plasma. These results suggest that lutein has the potential to act as an important antioxidant molecule in erythrocytes, and it thereby may contribute to the prevention of dementia. Therefore future biological and clinical studies will be required to evaluate the efficacy as well as safety of lutein in models of dementia with a realistic prospect of its use in human therapy.

  6. Influence of Ibuprofen on Phospholipid Membranes

    CERN Document Server

    Jaksch, Sebastian; Koutsioubas, Alexandros; Mattauch, Stefan; Holderer, Olaf; Ivanova, Oxana; Frielinghaus, Henrich; Hertrich, Samira; Nickel, Bert

    2014-01-01

    Basic understanding of biological membranes is of paramount importance as these membranes comprise the very building blocks of life itself. Cells depend in their function on a range of properties of the membrane, which are important for the stability and function of the cell, information and nutrient transport, waste disposal and finally the admission of drugs into the cell and also the deflection of bacteria and viruses. We have investigated the influence of ibuprofen on the structure and dynamics of L-alpha-phosphatidylcholine (SoyPC) membranes by means of grazing incidence small-angle neutron scattering (GISANS), neutron reflectometry and grazing incidence neutron spin echo spectroscopy (GINSES). From the results of these experiments we were able to determine that ibuprofen induces a two-step structuring behavior in the SoyPC films, where the structure evolves from the purely lamellar phase for pure SoyPC over a superposition of two hexagonal phases to a purely hexago- nal phase at high concentrations. Add...

  7. Accelerated extracellular matrix turnover during exacerbations of COPD

    DEFF Research Database (Denmark)

    Sand, Jannie M B; Knox, Alan J; Lange, Peter

    2015-01-01

    BACKGROUND: Exacerbations of chronic obstructive pulmonary disease (COPD) contribute significantly to disease progression. However, the effect on tissue structure and turnover is not well described. There is an urgent clinical need for biomarkers of disease activity associated with disease...... progression. Extracellular matrix (ECM) turnover reflects activity in tissues and consequently assessment of ECM turnover may serve as biomarkers of disease activity. We hypothesized that the turnover of lung ECM proteins were altered during exacerbations of COPD. METHODS: 69 patients with COPD hospitalised......, respectively), and degradation of elastin (ELM7 and EL-NE) and versican (VCANM). RESULTS: Circulating levels of C3M, C4M, C6M, ELM7, and EL-NE were elevated during an exacerbation of COPD as compared to follow-up (all P

  8. Work-life balance, job satisfaction and turnover intention amongst ...

    African Journals Online (AJOL)

    Work-life balance, job satisfaction and turnover intention amongst information ... AFRICAN JOURNALS ONLINE (AJOL) · Journals · Advanced Search · USING ... White employees had signifi cantly stronger experiences of job satisfaction and ...

  9. Achilles tendinosis: Changes in biochemical composition and collagen turnover rate

    NARCIS (Netherlands)

    Mos, M. de; El, B. van; Groot, J. de; Jahr, H.; Schie, H.T.M. van; Arkel, E.R. van; Tol, H.; Heijboer, R.; Osch, G.J.V.M. van; Verhaar, J.A.N.

    2007-01-01

    Background: Understanding biochemical and structural changes of the extracellular matrix in Achilles tendinosis might be important for developing mechanism-based therapies. Hypothesis: In Achilles tendinosis, changes occur in biochemical composition and collagen turnover rate. Study Design: Descript

  10. Achilles tendinosis - Changes in biochemical composition and collagen turnover rate

    NARCIS (Netherlands)

    de Mos, Marieke; van El, Benno; DeGroot, Jeroen; Jahr, Holger; van Schie, Hans T. M.; van Arkel, Ewoud R.; Tol, Hans; Heijboer, Rien; van Osch, Gerjo J. V. M.; Verhaar, Jan A. N.

    2007-01-01

    Background: Understanding biochemical and structural changes of the extracellular matrix in Achilles tendinosis might be important for developing mechanism-based therapies. Hypothesis: In Achilles tendinosis, changes occur in biochemical composition and collagen turnover rate. Study Design: Descript

  11. Exposure to negative acts and risk of turnover

    DEFF Research Database (Denmark)

    Clausen, Thomas; Hansen, Jørgen V.; Høgh (Hogh), Annie;

    2016-01-01

    -year (instead of a 1-year) follow-up period the association between bullying and turnover remained statistically significant in office workers even after adjusting for depressive symptoms (OR 2.10, 95 % CI 1.17-3.76). We found no statistically significant associations between threats of violence......PURPOSE: To investigate whether self-reported exposure to negative acts in the workplace (bullying and threats of violence) predicted turnover in three occupational groups (human service and sales workers, office workers and manual workers). METHODS: Survey data on 2766 respondents were combined...... exposure to negative acts (bullying and threats of violence) and risk of turnover. When participants were stratified by occupational group and analyses were adjusted for age, gender, tenure and psychosocial working conditions, we found that exposure to bullying predicted risk of turnover in office workers...

  12. Regulation of endoplasmic reticulum turnover by selective autophagy

    NARCIS (Netherlands)

    Khaminets, Aliaksandr; Heinrich, Theresa; Mari, Muriel; Grumati, Paolo; Huebner, Antje K.; Akutsu, Masato; Liebmann, Lutz; Stolz, Alexandra; Nietzsche, Sandor; Koch, Nicole; Mauthe, Mario; Katona, Istvan; Qualmann, Britta; Weis, Joachim; Reggiori, Fulvio; Kurth, Ingo; Huebner, Christian A.; Dikic, Ivan

    2015-01-01

    The endoplasmic reticulum (ER) is the largest intracellular endomembrane system, enabling protein and lipid synthesis, ion homeostasis, quality control of newly synthesized proteins and organelle communication(1). Constant ER turnover and modulation is needed to meet different cellular requirements

  13. DAMPAK WORK FAMILY CONFLICT PEKERJA WANITA TERHADAP ABSEN DAN TURNOVER

    Directory of Open Access Journals (Sweden)

    Gendut Sukarno

    2005-01-01

    Full Text Available Penelitian ini bertujuan untuk menganalisis Model Konseptual Work Family Conflict dalam kaitannya dengan absen dan Turnover. Diharapkan dapat membantu Pimpinan perusahaan dalam mengelola konflik antar kepentingan perusahaan dan keluarga, agar tidak berdampak terhadap meningkatnya absensi dan turnover . Sampel dalam penelitian ini adalah karyawan wanita yang bekerja di 20 bank swasta di Surabaya sebagai responden sebanyak 150 orang. Teknik analisis yang digunakan  adalah Structural Equation Modeling [SEM] dengan program AMOS 4,0. Hasil pengujian menunjukkan bahwa faktor work-family conflict berpengaruh terhadap faktor absen tidak dapat diterima. Faktor work-family conflict berpengaruh terhadap faktor turnover tidak dapat diterima, serta faktor absen berpengaruh terhadap faktor turnover dapat diterima.

  14. Regulation of endoplasmic reticulum turnover by selective autophagy

    NARCIS (Netherlands)

    Khaminets, Aliaksandr; Heinrich, Theresa; Mari, Muriel; Grumati, Paolo; Huebner, Antje K; Akutsu, Masato; Liebmann, Lutz; Stolz, Alexandra; Nietzsche, Sandor; Koch, Nicole; Mauthe, Mario; Katona, Istvan; Qualmann, Britta; Weis, Joachim; Reggiori, Fulvio; Kurth, Ingo; Hübner, Christian A; Dikic, Ivan

    2015-01-01

    The endoplasmic reticulum (ER) is the largest intracellular endomembrane system, enabling protein and lipid synthesis, ion homeostasis, quality control of newly synthesized proteins and organelle communication. Constant ER turnover and modulation is needed to meet different cellular requirements and

  15. Regulation of endoplasmic reticulum turnover by selective autophagy

    NARCIS (Netherlands)

    Khaminets, Aliaksandr; Heinrich, Theresa; Mari, Muriel; Grumati, Paolo; Huebner, Antje K.; Akutsu, Masato; Liebmann, Lutz; Stolz, Alexandra; Nietzsche, Sandor; Koch, Nicole; Mauthe, Mario; Katona, Istvan; Qualmann, Britta; Weis, Joachim; Reggiori, Fulvio; Kurth, Ingo; Huebner, Christian A.; Dikic, Ivan

    2015-01-01

    The endoplasmic reticulum (ER) is the largest intracellular endomembrane system, enabling protein and lipid synthesis, ion homeostasis, quality control of newly synthesized proteins and organelle communication(1). Constant ER turnover and modulation is needed to meet different cellular requirements

  16. Achilles tendinosis: Changes in biochemical composition and collagen turnover rate

    NARCIS (Netherlands)

    Mos, M. de; El, B. van; Groot, J. de; Jahr, H.; Schie, H.T.M. van; Arkel, E.R. van; Tol, H.; Heijboer, R.; Osch, G.J.V.M. van; Verhaar, J.A.N.

    2007-01-01

    Background: Understanding biochemical and structural changes of the extracellular matrix in Achilles tendinosis might be important for developing mechanism-based therapies. Hypothesis: In Achilles tendinosis, changes occur in biochemical composition and collagen turnover rate. Study Design:

  17. Achilles tendinosis - Changes in biochemical composition and collagen turnover rate

    NARCIS (Netherlands)

    de Mos, Marieke; van El, Benno; DeGroot, Jeroen; Jahr, Holger; van Schie, Hans T. M.; van Arkel, Ewoud R.; Tol, Hans; Heijboer, Rien; van Osch, Gerjo J. V. M.; Verhaar, Jan A. N.

    Background: Understanding biochemical and structural changes of the extracellular matrix in Achilles tendinosis might be important for developing mechanism-based therapies. Hypothesis: In Achilles tendinosis, changes occur in biochemical composition and collagen turnover rate. Study Design:

  18. Report: Remedial Project Manager Turnover at Superfund Sites

    Science.gov (United States)

    Report #2001-M-000015, June 15, 2001. We determined that EPA Region III did not have formal procedures in place to mitigate continuity problems caused by turnover of EPA personnel in the Superfund program.

  19. Achilles tendinosis - Changes in biochemical composition and collagen turnover rate

    NARCIS (Netherlands)

    de Mos, Marieke; van El, Benno; DeGroot, Jeroen; Jahr, Holger; van Schie, Hans T. M.; van Arkel, Ewoud R.; Tol, Hans; Heijboer, Rien; van Osch, Gerjo J. V. M.; Verhaar, Jan A. N.

    2007-01-01

    Background: Understanding biochemical and structural changes of the extracellular matrix in Achilles tendinosis might be important for developing mechanism-based therapies. Hypothesis: In Achilles tendinosis, changes occur in biochemical composition and collagen turnover rate. Study Design: Descript

  20. Achilles tendinosis: Changes in biochemical composition and collagen turnover rate

    NARCIS (Netherlands)

    Mos, M. de; El, B. van; Groot, J. de; Jahr, H.; Schie, H.T.M. van; Arkel, E.R. van; Tol, H.; Heijboer, R.; Osch, G.J.V.M. van; Verhaar, J.A.N.

    2007-01-01

    Background: Understanding biochemical and structural changes of the extracellular matrix in Achilles tendinosis might be important for developing mechanism-based therapies. Hypothesis: In Achilles tendinosis, changes occur in biochemical composition and collagen turnover rate. Study Design: Descript

  1. Electron paramagnetic resonance studies of magnetically aligned phospholipid bilayers utilizing a phospholipid spin label: the effect of cholesterol.

    Science.gov (United States)

    Dave, Paresh C; Nusair, Nisreen A; Inbaraj, Johnson J; Lorigan, Gary A

    2005-08-15

    X-band EPR spectroscopy has been employed to study the dynamic properties of magnetically aligned phospholipid bilayers (bicelles) utilizing a variety of phosphocholine spin labels (n-PCSL) as a function of cholesterol content. The utilization of both perpendicular and parallel aligned bicelles in EPR spectroscopy provides a more detailed structural and orientational picture of the phospholipid bilayers. The magnetically aligned EPR spectra of the bicelles and the hyperfine splitting values reveal that the addition of cholesterol increases the phase transition temperature and alignment temperature of the DMPC/DHPC bicelles. The corresponding molecular order parameter, Smol, of the DMPC/DHPC bicelles increased upon addition of cholesterol. Cholesterol also decreased the rotational motion and increased the degree of anisotropy in the interior region of the bicelles. This report reveals that the dynamic properties of DMPC/DHPC bicelles agree well with other model membrane systems and that the magnetically aligned bicelles are an excellent model membrane system.

  2. Liquid Crystal Gel Reduces Age Spots by Promoting Skin Turnover

    OpenAIRE

    Mina Musashi; Ariella Coler-Reilly; Teruaki Nagasawa; Yoshiki Kubota; Satomi Kato; Yoko Yamaguchi

    2014-01-01

    Studies have shown that liquid crystals structurally resembling the intercellular lipids in the stratum corneum can beneficially affect the skin when applied topically by stimulating the skin’s natural regenerative functions and accelerating epidermal turnover. In the present study, the effects of applying low concentrations of a liquid crystal gel of our own creation were evaluated using epidermal thickening in mouse skin as an assay for effective stimulation of epidermal turnover. A liquid ...

  3. Employee turnover in a financial institution / van Zyl M.

    OpenAIRE

    Van Zyl, Marie-Antoinette

    2011-01-01

    With recognition of turnover as a financial issue increasing, companies are searching for strategies to confront the problem in ways that generate a good return on investment. Successfully managing turnover is a matter of understanding its costs, causes and cures. In service–oriented industries such as banking, people are considered among the most important assets of a firm. Forward–thinking banks are looking for ways to leverage people, along with processes and technology, to achieve their o...

  4. Quantifying Assemblage Turnover and Species Contributions at Ecologic Boundaries

    OpenAIRE

    Hayek,Lee-Ann C.; Brent Wilson

    2013-01-01

    Not all boundaries, whether stratigraphical or geographical, are marked by species-level changes in community composition. For example, paleodata for some sites do not show readily discernible glacial-interglacial contrasts. Rather, the proportional abundances of species can vary subtly between glacials and interglacials. This paper presents a simple quantitative measure of assemblage turnover (assemblage turnover index, ATI) that uses changes in species' proportional abundances to identify i...

  5. Diabetes, Biochemical Markers of Bone Turnover, Diabetes Control, and Bone

    OpenAIRE

    Starup-Linde, Jakob

    2013-01-01

    Diabetes mellitus is known to have late complications including micro vascular and macro vascular disease. This review focuses on another possible area of complication regarding diabetes; bone. Diabetes may affect bone via bone structure, bone density, and biochemical markers of bone turnover. The aim of the present review is to examine in vivo from humans on biochemical markers of bone turnover in diabetics compared to non-diabetics. Furthermore, the effect of glycemic control on bone marker...

  6. Increased Concentration of Polyvalent Phospholipids in the Adsorption Domain of a Charged Protein

    CERN Document Server

    Haleva, E; Diamant, H; Haleva, Emir; Ben-Tal, Nir; Diamant, Haim

    2004-01-01

    We studied the adsorption of a charged protein onto an oppositely charged membrane, composed of mobile phospholipids of differing valence, using a statistical-thermodynamical approach. A two-block model was employed, one block corresponding to the protein-affected region on the membrane, referred to as the adsorption domain, and the other to the unaffected remainder of the membrane. We calculated the protein-induced lipid rearrangement in the adsorption domain as arising from the interplay between the electrostatic interactions in the system and the mixing entropy of the lipids. Equating the electrochemical potentials of the lipids in the two blocks yields an expression for the relations among the various lipid fractions in the adsorption domain, indicating a sensitive (exponential) dependence on lipid valence. This expression is a result of the two-block picture but does not depend on further details of the protein-membrane interaction. We subsequently calculated the lipid fractions themselves using the Pois...

  7. Mechanics and dynamics of triglyceride-phospholipid model membranes: Implications for cellular properties and function.

    Science.gov (United States)

    Pakkanen, Kirsi I; Duelund, Lars; Qvortrup, Klaus; Pedersen, Jan S; Ipsen, John H

    2011-08-01

    We demonstrate here that triolein alters the mechanical properties of phospholipid membranes and induces extraordinary conformational dynamics. Triolein containing membranes exhibit fluctuations up to size range of 100μm and with the help of these are e.g. able to squeeze through narrow passages between neighbouring structures. Triolein-phosphatidylcholine membranes were found to have bending rigidity significantly lower than that of corresponding pure phosphatidylcholine membrane. Moreover, the triolein containing membranes were found to be reluctant to fuse, which is in good accordance with larger lamellar distances observed in the TOPOPC membranes. These findings suggest repulsion between adjacent membranes. We provide a comprehensive discussion on the possible explanations for the observed mechanics and dynamics in the TOPOPC system and on their potential cellular implications. Copyright © 2011 Elsevier B.V. All rights reserved.

  8. Interference of a short-chain phospholipid with ion transport pathways in frog skin

    DEFF Research Database (Denmark)

    Unmack, M A; Frederiksen, O; Willumsen, N J

    1997-01-01

    The effects of mucosal application of the short-chain phospholipid didecanoyl-L-alpha-phosphatidylcholine (DDPC; with two saturated 10-carbon acyl chains) on active Na+ transport and transepithelial conductance (G) in the frog skin (Rana temporaria) were investigated. Active Na+ transport...... was measured as the amiloride-sensitive short-circuit current (ISC) and G was determined from transepithelial voltage-clamp pulses under short-circuit conditions. DDPC dose-dependently inhibited ISC with an ID50 of about 0.05% (w/v) and a maximal effect ( approximately 55%) at >/= 1% DDPC. G increased...... in G by DDPC, these results suggest that the DDPC-induced increase in G represents an increase in the paracellular shunt conductance. The effects of mucosal DDPC were almost fully reversible within 8 h. The results indicate that DDPC inhibits amiloride-sensitive Na+ channels in the apical membrane...

  9. Aqueous solutions at the interface with phospholipid bilayers.

    Science.gov (United States)

    Berkowitz, Max L; Vácha, Robert

    2012-01-17

    In a sense, life is defined by membranes, because they delineate the barrier between the living cell and its surroundings. Membranes are also essential for regulating the machinery of life throughout many interfaces within the cell's interior. A large number of experimental, computational, and theoretical studies have demonstrated how the properties of water and ionic aqueous solutions change due to the vicinity of membranes and, in turn, how the properties of membranes depend on the presence of aqueous solutions. Consequently, understanding the character of aqueous solutions at their interface with biological membranes is critical to research progress on many fronts. The importance of incorporating a molecular-level description of water into the study of biomembrane surfaces was demonstrated by an examination of the interaction between phospholipid bilayers that can serve as model biological membranes. The results showed that, in addition to well-known forces, such as van der Waals and screened Coulomb, one has to consider a repulsion force due to the removal of water between surfaces. It was also known that physicochemical properties of biological membranes are strongly influenced by the specific character of the ions in the surrounding aqueous solutions because of the observation that different anions produce different effects on muscle twitch tension. In this Account, we describe the interaction of pure water, and also of aqueous ionic solutions, with model membranes. We show that a symbiosis of experimental and computational work over the past few years has resulted in substantial progress in the field. We now better understand the origin of the hydration force, the structural properties of water at the interface with phospholipid bilayers, and the influence of phospholipid headgroups on the dynamics of water. We also improved our knowledge of the ion-specific effect, which is observed at the interface of the phospholipid bilayer and aqueous solution, and its

  10. Effects of Fructus Ligustri Lucidi extract on bone turnover and calcium balance in ovariectomized rats.

    Science.gov (United States)

    Zhang, Yan; Lai, Wan-Ping; Leung, Ping-Chung; Wu, Chun-Fu; Yao, Xin-Sheng; Wong, Man-Sau

    2006-02-01

    The aim of this study was to evaluate the effect of Fructus Ligustri Lucidi (FLL), a kidney-tonifying Chinese herbal medicine, on the biochemical markers of bone turnover, calcium metabolism and balance in osteoporotic rat model developed by ovariectomy. Four weeks after surgical operation, animals were randomly assigned to one of the four treatments for 14 weeks: sham-operated control treated with vehicle (sham, n=8), ovariectomized group treated with vehicle (OVX, n=8), OVX group treated with 17beta-estradiol (E(2), n=10, 2 microg/kg/d) and OVX group treated with FLL extracts (FLL, n=10, 550 mg/kg/d). Serum osteocalcin and urinary deoxypyridinoline levels were upregulated in rats in response to OVX, suggesting that the bone turnover rate was accelerated in these animals. Treatment of OVX rats with FLL extract could prevent OVX-induced increase in bone turnover by suppression of both serum osteocalcin (pcalcium in rats by increasing the intestinal calcium absorption rate (pcalcium content (pcalcium balance in OVX rats and it might be a potential candidate for prevention and treatment of postmenopausal osteoporosis.

  11. Reduced cell turnover in lymphocytic monkeys infected by human T-lymphotropic virus type 1.

    Science.gov (United States)

    Debacq, Christophe; Héraud, Jean-Michel; Asquith, Becca; Bangham, Charles; Merien, Fabrice; Moules, Vincent; Mortreux, Franck; Wattel, Eric; Burny, Arsène; Kettmann, Richard; Kazanji, Mirdad; Willems, Luc

    2005-11-17

    Understanding cell dynamics in animal models have implications for therapeutic strategies elaborated against leukemia in human. Quantification of the cell turnover in closely related primate systems is particularly important for rare and aggressive forms of human cancers, such as adult T-cell leukemia. For this purpose, we have measured the death and proliferation rates of the CD4+ T lymphocyte population in squirrel monkeys (Saimiri sciureus) infected by human T-lymphotropic virus type 1 (HTLV-1). The kinetics of in vivo bromodeoxyuridine labeling revealed no modulation of the cell turnover in HTLV-1-infected monkeys with normal CD4 cell counts. In contrast, a substantial decrease in the proliferation rate of the CD4+ T population was observed in lymphocytic monkeys (e.g. characterized by excessive proportions of CD4+ T lymphocytes and by the presence of abnormal flower-like cells). Unexpectedly, onset of HTLV-associated leukemia thus occurs in the absence of increased CD4+ T-cell proliferation. This dynamics significantly differs from the generalized activation of the T-cell turnover induced by other primate lymphotropic viruses like HIV and SIV.

  12. Plant species persistence and turnover on small Bahamian islands.

    Science.gov (United States)

    Morrison, Lloyd W

    2003-06-01

    I conducted surveys of the plant species occupying 136 small islands in the Exuma Cays and 58 small islands near Andros, Bahamas. Most species occurred on relatively few islands, and most islands contained relatively few species. Identities of the most common species differed between the two archipelagos. Comparisons with earlier surveys revealed species extinctions and immigrations. Turnover was relatively low on both a per island and a per species basis on both archipelagos, although significant spatial variation in turnover rates between archipelagos was found. Most islands experienced no turnover; islands on which turnover did occur were larger and had higher species richness. Likewise, most species did not turnover, although much variation existed in turnover rates among those that did. Experimental introductions of two species to very small islands naturally devoid of vegetation revealed that these islands could support plant life. One species survived on eight of ten islands for >9 years, including the effects of a moderate (class 2) hurricane. This hurricane caused substantial damage and loss of plant biomass, but resulted in no species extinctions on 30 small islands. Data for the small islands in this region, now spanning almost a decade, reveal that most populations are persistent over periods of years to decades, rarely going extinct or immigrating. Even moderate hurricanes seem to have little impact on species compositions.

  13. Long-period astronomical forcing of mammal turnover.

    Science.gov (United States)

    van Dam, Jan A; Abdul Aziz, Hayfaa; Alvarez Sierra, M Angeles; Hilgen, Frederik J; van den Hoek Ostende, Lars W; Lourens, Lucas J; Mein, Pierre; van der Meulen, Albert J; Pelaez-Campomanes, Pablo

    2006-10-12

    Mammals are among the fastest-radiating groups, being characterized by a mean species lifespan of the order of 2.5 million years (Myr). The basis for this characteristic timescale of origination, extinction and turnover is not well understood. Various studies have invoked climate change to explain mammalian species turnover, but other studies have either challenged or only partly confirmed the climate-turnover hypothesis. Here we use an exceptionally long (24.5-2.5 Myr ago), dense, and well-dated terrestrial record of rodent lineages from central Spain, and show the existence of turnover cycles with periods of 2.4-2.5 and 1.0 Myr. We link these cycles to low-frequency modulations of Milankovitch oscillations, and show that pulses of turnover occur at minima of the 2.37-Myr eccentricity cycle and nodes of the 1.2-Myr obliquity cycle. Because obliquity nodes and eccentricity minima are associated with ice sheet expansion and cooling and affect regional precipitation, we infer that long-period astronomical climate forcing is a major determinant of species turnover in small mammals and probably other groups as well.

  14. Synthesis of sn-1 functionalized phospholipids as substrates for secretory phospholipase A2

    DEFF Research Database (Denmark)

    Linderoth, Lars; Peters, Günther H.J.; Jørgensen, K.;

    2007-01-01

    Secretory phospholipase A2 (sPLA2) represents a family of small water-soluble enzymes that catalyze the hydrolysis of phospholipids in the sn-2 position liberating free fatty acids and lysophospholipids. Herein we report the synthesis of two new phospholipids (1 and 2) with bulky allyl......-substituents attached to the sn-1 position of the glycerol backbone. The synthesis of phospholipids 1 and 2 is based upon the construction of a key aldehyde intermediate 3 which locks the stereochemistry in the sn-2 position of the final phospholipids. The aldehyde functionality serves as the site for insertion...... of the allyl-substituents by a zinc mediated allylation. Small unilamellar liposomes composed of phospholipids 1 and 2 were subjected to sPLA2 activity measurements. Our results show that only phospholipid 1 is hydrolyzed by the enzyme. Molecular dynamics simulations revealed that the lack of hydrolysis...

  15. Composition and fatty acid distribution of bovine milk phospholipids from processed milk products.

    Science.gov (United States)

    Gallier, Sophie; Gragson, Derek; Cabral, Charles; Jiménez-Flores, Rafael; Everett, David W

    2010-10-13

    The aim of this work was to assess the accuracy of different extraction methods of phospholipids and to measure the effect that processing has on phospholipid composition. Four methods of extracting phospholipids from buttermilk powder were compared to optimize recovery of sphingomyelin. Using the optimal method, the phospholipid profile of four dairy products (raw milk, raw cream, homogenized and pasteurized milk, and buttermilk powder) was determined. A total lipid extraction by the Folch method followed by a solid-phase extraction using the Bitman method was the most efficient technique to recover milk sphingomyelin. Milk processing (churning, centrifuging, homogenization, spray-drying) affected the profile of milk phospholipids, leading to a loss of sphingomyelin and phosphatidylcholine after centrifugation for cream separation. A corresponding decrease in the saturation content of the raw cream phospholipids and a loss of phosphatidylethanolamine after spray-drying to produce buttermilk powder were also observed.

  16. Lipin-1 regulation of phospholipid synthesis maintains endoplasmic reticulum homeostasis and is critical for triple-negative breast cancer cell survival.

    Science.gov (United States)

    He, Jingquan; Zhang, Feng; Tay, Li Wei Rachel; Boroda, Salome; Nian, Weiqi; Levental, Kandice R; Levental, Ilya; Harris, Thurl E; Chang, Jeffrey T; Du, Guangwei

    2017-03-27

    Cancer cells reprogram their metabolism to increase the synthesis of macromolecules for rapid proliferation. Compared to fatty acids, much less is known about the synthesis of phospholipids, which is essential for membrane biogenesis in cancer cells. We found that LPIN1, which encodes lipin-1, a phosphatidic acid phosphatase (PAP) controlling the rate-limiting step in the phospholipid synthesis pathway, is highly up-regulated in basal-like triple-negative breast cancer (TNBC). Moreover, high LPIN1 expression correlates with the poor prognosis of these patients. Knockdown of LPIN1 increases apoptosis in basal-like TNBC cell lines, whereas it has minimal or less effect on normal human mammary gland epithelial cells (HMECs) and estrogen receptor-positive breast cancer cell lines. Fatty acid incorporation and lipidomics analyses showed that LPIN1 knockdown blocks phospholipid synthesis and changes membrane lipid compositions that ultimately induce the activation of 1 of the 3 branches of unfolded protein responses, the inositol-requiring enzyme-1α pathway. We also show for the first time, to our knowledge, that lipin-1 knockdown significantly inhibits tumor growth in vivo using an orthotopic xenograft breast mouse model. Our results suggest that lipin-1 is a potential target for cancer therapy.-He, J., Zhang, F., Tay, L. W. R., Boroda, S., Nian, W., Levental, K. R., Levental, I., Harris, T. E., Chang, J. T., Du, G. Lipin-1 regulation of phospholipid synthesis maintains endoplasmic reticulum homeostasis and is critical for triple-negative breast cancer cell survival.

  17. A review on phospholipids and their main applications in drug delivery systems

    OpenAIRE

    Jing Li; Xuling Wang; Ting Zhang; Chunling Wang; Zhenjun Huang; Xiang Luo; Yihui Deng

    2015-01-01

    Phospholipids have the characteristics of excellent biocompatibility and a especial amphiphilicity. These unique properties make phospholipids most appropriate to be employed as important pharmaceutical excipients and they have a very wide range of applications in drug delivery systems. The aim of this review is to summarize phospholipids and some of their related applications in drug delivery systems, and highlight the relationship between the properties and applications, and the effect of t...

  18. Update on anti-phospholipid antibodies in SLE: the Hopkins' Lupus Cohort.

    Science.gov (United States)

    Petri, M

    2010-04-01

    Anti-phospholipid antibodies are common in patients in the Hopkins' Lupus Cohort: 47% have anti-cardiolipin, 32.5% anti-beta(2)-glycoprotein I and 26% lupus anticoagulant (by dRVVT confirmatory testing). Systemic lupus erythematosus patients with the lupus anticoagulant at baseline have a 50% chance of a deep venous thrombosis/pulmonary embolus in the next 20 years. Anti-phospholipid antibodies differ in their association with thrombosis: the lupus anticoagulant is most strongly associated with arterial and venous thrombosis and is the only anti-phospholipid antibody associated with myocardial infarction. Anti-phospholipid antibodies are not associated with atherosclerosis.

  19. Formation of oil-in-water emulsions from natural emulsifiers using spontaneous emulsification: sunflower phospholipids.

    Science.gov (United States)

    Komaiko, Jennifer; Sastrosubroto, Ashtri; McClements, David Julian

    2015-11-18

    This study examined the possibility of producing oil-in-water emulsions using a natural surfactant (sunflower phospholipids) and a low-energy method (spontaneous emulsification). Spontaneous emulsification was carried out by titrating an organic phase (oil and phospholipid) into an aqueous phase with continuous stirring. The influence of phospholipid composition, surfactant-to-oil ratio (SOR), initial phospholipids location, storage time, phospholipid type, and preparation method was tested. The initial droplet size depended on the nature of the phospholipid used, which was attributed to differences in phospholipid composition. Droplet size decreased with increasing SOR and was smallest when the phospholipid was fully dissolved in the organic phase rather than the aqueous phase. The droplets formed using spontaneous emulsification were relatively large (d > 10 μm), and so the emulsions were unstable to gravitational separation. At low SORs (0.1 and 0.5), emulsions produced with phospholipids had a smaller particle diameter than those produced with a synthetic surfactant (Tween 80), but at a higher SOR (1.0), this trend was reversed. High-energy methods (microfluidization and sonication) formed significantly smaller droplets (d < 10 μm) than spontaneous emulsification. The results from this study show that low-energy methods could be utilized with natural surfactants for applications for which fine droplets are not essential.

  20. Comprehensive approach to the quantitative analysis of mitochondrial phospholipids by HPLC-MS.

    Science.gov (United States)

    Kim, Junhwan; Hoppel, Charles L

    2013-01-01

    A normal-phase HPLC-MS method was established to analyze mitochondrial phospholipids quantitatively as well as qualitatively. An efficient extraction procedure and chromatographic conditions were developed using twelve standardized phospholipids and lysophospholipids. The chromatographic conditions provided physical separation of phospholipids by class, and efficient ionization allowed detection of low abundance phospholipids such as phosphatidylglycerol and monolysocardiolipin. The chromatographic separation of each class of phospholipid permitted qualitative identification of molecular species without interference from other classes. This is advantageous for mitochondrial lipidomics because the composition of mitochondrial phospholipids varies depending on tissue source, pathological condition, and nutrition. Using the method, seven classes of phospholipids (phosphatidylethanolamine, phosphatidylcholine, phosphatidylglycerol, phosphatidylinositol, phosphatidylserine, cardiolipin, and monolysocardiolipin) were detected in rat heart and skeletal muscle mitochondria and all but phosphatidylserine were quantified. The concentration was calculated using standard curves with an internal standard generated for each class of phospholipid. The method was validated for intraday and interday variation and showed excellent reproducibility and accuracy. This new method, with each step documented, provides a powerful tool for accurate quantitation of phospholipids, a basic structural component of mitochondrial membranes.

  1. Type VI collagen turnover-related peptides—novel serological biomarkers of muscle mass and anabolic response to loading in young men

    DEFF Research Database (Denmark)

    Nedergaard, Anders; Sun, Shu; Karsdal, Morten A

    2013-01-01

    Immobilization-induced loss of muscle mass is a complex phenomenon with several parallels to sarcopenic and cachectic muscle loss. Muscle is a large organ with a protein turnover that is orders of magnitude larger than most other tissues. Thus, we hypothesize that muscle loss and regain is reflec......Immobilization-induced loss of muscle mass is a complex phenomenon with several parallels to sarcopenic and cachectic muscle loss. Muscle is a large organ with a protein turnover that is orders of magnitude larger than most other tissues. Thus, we hypothesize that muscle loss and regain...... is reflected by peptide biomarkers derived from type VI collagen processing released in the circulation....

  2. Lignin as a molecular marker of land management impacts on soil C storage and turnover

    Science.gov (United States)

    Panettieri, Marco; Rumpel, Cornelia; Dignac, Marie-France; Billiou, Daniel; Chabbi, Abad

    2017-04-01

    Implementation of temporary grassland on cropped lands may be a sustainable option to enhance the carbon storage via the accumulation of soil organic matter (SOM). However, carbon storage is not only a matter of quantity, since higher inputs of labile carbon may stimulate soil microbial and fungal communities and induce the degradation of the formerly stabilized SOM, through the so-called priming effect. Therefore, targeted strategies for carbon storage need to consider the stability of newly added SOM at long term. Recently, soil ecologist emphasized the huge spatial variability of soil structure and properties, and the fact that many ecosystem functions of SOM are only achieved if it decomposes. Thus, more attention must be paid to fluxes of carbon rather than to the quantities accumulated. The present study aims to cope with the listed problems. The aim of the study was to use lignin as a molecular marker of plant C turnover, to assess carbon storage provided by a temporary (ley) grassland system situated at the long term experimental observatory in Lusignan (http://www.soere-acbb.com/). Our conceptual approach included plots under permanent grassland, permanent cropland and bare fallow as controls. A soil fractionation into water stable aggregates has been chosen as a strategy to overcome spatial complexity, and compound specific analyses were focused on lignin phenols within the aggregates. The hypothesis of this work is that lignin turnovers may be influenced by land uses, lignin localisation within soil compartments, the nature of litter input (above vs. belowground biomass), aggregate distribution, and plant cover characteristics (crop vs. grass). To test the hypothesis, cycles of storage and degradation of lignin were studied using compound specific stable isotope probing, taking advantage of in situ labelling provided by the switches from C3 to C4 plants (i.e. grassland to continuous maize) in the experimental area. Lignin monophenols were extracted and

  3. A case study into labour turnover within an NHS Trust.

    Science.gov (United States)

    Bamford, David; Hall, Catherine

    2007-02-01

    This paper investigates turnover in a British NHS Trust, to find out why staff left and whether factors identified in the literature with regards to improving turnover were pertinent to the organization. The research also investigated staff groups with high turnover--staff with less than 12 months service, and the unqualified nursing staff group--to ascertain whether there were any reasons for leaving or areas of dissatisfaction particular to these groups. The outcomes of the research complied with much of the published research with some interesting differences. The main reasons for leaving were identified as moving house, promotion or career development and taking up education and training opportunities elsewhere. There was no evidence of 'level of pay', commonly given as a significant influence behind turnover, as a reason for leaving. It was also found that the retention strategies identified in the published research were mainly applicable to the research, with evidence to support the improvement of line management skills, training and development, career development, appraisal, communications and induction in order to reduce turnover. There was less evidence for introducing work-life balance policies, improving communications, pay and working relationships as retention strategies. Recommendations for future management of labour turnover within the NHS Trust and elsewhere are made, with observations about the validity of some existing models. The core contribution of this research is in adding to the body of knowledge about labour turnover issues. This is of value to those working in the UK health-care and wider public sector. Specific recommendations for future research are made.

  4. Metabolic activity and collagen turnover in human tendon in response to physical activity

    DEFF Research Database (Denmark)

    Kjaer, M; Langberg, H; Miller, B F

    2005-01-01

    Connective tissue of the human tendon plays an important role in force transmission. The extracellular matrix turnover of tendon is influenced by physical activity. Blood flow, oxygen demand, and the level of collagen synthesis and matrix metalloproteinases increase with mechanical loading. Gene ...... of overuse tendon injuries occurring during sport, work or leisure-related activities....... as of extracellular matrix formation. These changes may contribute to training-induced adaptation of biomechanical properties consisting of altered resistance to loading and enhanced tolerance to strenuous exercise. Understanding of such changes is a pre-requisite in the development of measures aimed at prevention...

  5. Slow Phospholipid Exchange between a Detergent-Solubilized Membrane Protein and Lipid-Detergent Mixed Micelles: Brominated Phospholipids as Tools to Follow Its Kinetics

    Science.gov (United States)

    Montigny, Cédric; Dieudonné, Thibaud; Orlowski, Stéphane; Vázquez-Ibar, José Luis; Gauron, Carole; Georgin, Dominique; Lund, Sten; le Maire, Marc; Møller, Jesper V.; Champeil, Philippe

    2017-01-01

    Membrane proteins are largely dependent for their function on the phospholipids present in their immediate environment, and when they are solubilized by detergent for further study, residual phospholipids are critical, too. Here, brominated phosphatidylcholine, a phospholipid which behaves as an unsaturated phosphatidylcholine, was used to reveal the kinetics of phospholipid exchange or transfer from detergent mixed micelles to the environment of a detergent-solubilized membrane protein, the paradigmatic P-type ATPase SERCA1a, in which Trp residues can experience fluorescence quenching by bromine atoms present on phospholipid alkyl chains in their immediate environment. Using dodecylmaltoside as the detergent, exchange of (brominated) phospholipid was found to be much slower than exchange of detergent under the same conditions, and also much slower than membrane solubilization, the latter being evidenced by light scattering changes. The kinetics of this exchange was strongly dependent on temperature. It was also dependent on the total concentration of the mixed micelles, revealing the major role for such exchange of the collision of detergent micelles with the detergent-solubilized protein. Back-transfer of the brominated phospholipid from the solubilized protein to the detergent micelle was much faster if lipid-free DDM micelles instead of mixed micelles were added for triggering dissociation of brominated phosphatidylcholine from the solubilized protein, or in the additional presence of C12E8 detergent during exchange, also emphasizing the role of the chemical nature of the micelle/protein interface. This protocol using brominated lipids appears to be valuable for revealing the possibly slow kinetics of phospholipid transfer to or from detergent-solubilized membrane proteins. Independently, continuous recording of the activity of the protein can also be used in some cases to correlate changes in activity with the exchange of a specific phospholipid, as shown here

  6. Sphingophosphonolipids, phospholipids, and fatty acids from Aegean jellyfish Aurelia aurita.

    Science.gov (United States)

    Kariotoglou, D M; Mastronicolis, S K

    2001-11-01

    The goal of this study is to elucidate and identify several sphingophosphonolipids from Aurelia aurita, an abundant but harmless Aegean jellyfish, in which they have not previously been described. Total lipids of A. aurita were 0.031-0.036% of fresh tissue, and the lipid phosphorus content was 1.3-1.7% of total lipids. Phosphonolipids were 21.7% of phospholipids and consisted of a major ceramide aminoethylphosphonate (CAEP-I; 18.3%), as well as three minor CAEP (II, III, IV) methyl analogs at 1.3, 1.1, and 1.0%, respectively. The remaining phospholipid composition was: phosphatidylcholine, 44.5%, including 36.2% glycerylethers; phosphatidylethanolamine, 18.6%, including 4.5% glycerylethers; cardiolipin, 5.6%; phosphatidylinositol, 2.6%; and lysophosphatidylcholine, 5.0%. In CAEP-I, saturated fatty acids of 14-18 carbon chain length were 70.8% and were combined with 57.3% dihydroxy bases and 23.4% trihydroxy bases. The suite of the three minor CAEP methyl analogs were of the same lipid class based on the head group, but they separated into three different components because of their polarity as follows: CAEP-II and CAEP-III differentiation from the major CAEP-I was mainly due to the increased fatty acid unsaturation and not to a different long-chain base, but the CAEP-IV differentiation from CAEP-I, apart from fatty acid unsaturation, was due to the increased content of hydroxyl groups originated from both hydroxy fatty acids and trihydroxy long-chain bases. Saturated fatty acids were predominant in total (76.7%), polar (83.0%), and neutral lipids (67.6%) of A. aurita. The major phospholipid components of A. aurita were comparable to those previously found in a related organism (Pelagia noctiluca), which can injure humans.

  7. Phospholipid and Hydrocarbon Interactions with a Charged Electrode Interface.

    Science.gov (United States)

    Levine, Zachary A; DeNardis, Nadica Ivošević; Vernier, P Thomas

    2016-03-22

    Using a combination of molecular dynamics simulations and experiments we examined the interactions of alkanes and phospholipids at charged interfaces in order to understand how interfacial charge densities affect the association of these two representative molecules with electrodes. Consistent with theory and experiment, these model systems reveal interfacial associations mediated through a combination of Coulombic and van der Waals forces. van der Waals forces, in particular, mediate rapid binding of decane to neutral electrodes. No decane binding was observed at high surface charge densities because of interfacial water polarization, which screens hydrophobic attractions. The positively charged choline moiety of the phospholipid palmitoyloleoylphosphatidylcholine (POPC) is primarily responsible for POPC attraction by a moderately negatively charged electrode. The hydrocarbon tails of POPC interact with the hydrophobic electrode interface similarly to decane. Previously reported electrochemical results confirm these findings by demonstrating bipolar displacement currents from PC vesicles adhering to moderately negatively charged interfaces, originating from the choline interactions observed in simulations. At more negatively charged interfaces, choline-to-surface binding was stronger. In both simulations and experiments the maximal interaction of anionic PS occurs with a positively charged interface, provided that the electrostatic forces outweigh local Lennard-Jones interactions. Direct comparisons between the binding affinities measured in experiments and those obtained in simulations reveal previously unobserved atomic interactions that facilitate lipid vesicle adhesion to charged interfaces. Moreover, the implementation of a charged interface in molecular dynamics simulations provides an alternative method for the generation of large electric fields across phospholipid bilayers, especially for systems with periodic boundary conditions, and may be useful for

  8. Magnetic field alignable domains in phospholipid vesicle membranes containing lanthanides.

    Science.gov (United States)

    Beck, Paul; Liebi, Marianne; Kohlbrecher, Joachim; Ishikawa, Takashi; Rüegger, Heinz; Zepik, Helmut; Fischer, Peter; Walde, Peter; Windhab, Erich

    2010-01-14

    Magnetic fields were applied as a structuring force on phospholipid-based vesicular systems, using paramagnetic lanthanide ions as magnetic handles anchored to the vesicle membrane. Different vesicle formulations were investigated using small angle neutron scattering (SANS) in a magnetic field of up to 8 T, cryo-transmission electron microscopy (cryo-TEM), (31)P NMR spectroscopy, dynamic light scattering (DLS), and permeability measurements with a fluorescent water-soluble marker (calcein). The investigated vesicle formulations consisted usually of 80 mol % of the phospholipid 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and 20 mol % of a chelator lipid (DMPE-DTPA; 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine-diethylenetriaminepentaacetate) with complexed lanthanide ions (Tm(3+), Dy(3+), or La(3+)), and the total lipid concentration was 15 mM. Vesicles containing the paramagnetic lanthanide Tm(3+) or Dy(3+) exhibited a temperature-dependent response to magnetic fields, which can be explained by considering the formation of lipid domains, which upon reaching a critical size become alignable in a magnetic field. The features of this "magnetic field alignable domain model" are as follows: with decreasing temperature (from 30 to 2.5 degrees C) solid domains, consisting mainly of the higher melting phospholipid (DMPE-DTPA.lanthanide), begin to form and grow in size. The domains assemble the large magnetic moments conferred by the lanthanides and orient in magnetic fields. The direction of alignment depends on the type of lanthanide used. The domains orient with their normal parallel to the magnetic field with thulium (Tm(3+)) and perpendicular with dysprosium (Dy(3+)). No magnetic field alignable domains were observed if DMPE-DTPA is replaced either by POPE-DTPA (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine-diethylenetriamine-pentaacetate) or by DMPC (1,2-dimyristoyl-sn-glycero-3-phosphocholine).

  9. N-acylethanolamines and precursor phospholipids - Relation to cell injury

    DEFF Research Database (Denmark)

    Hansen, Harald S.; Moesgaard, B.; Hansen, H.H.

    2000-01-01

    mitochondria, and direct inhibition of ceramidase. Anandamide (20:4-NAE) is formed as a minor component along with other NAEs during cell injury. Whether 20:4-NAE has a separate physiological role is at present not known, but some data suggest that 20:4-NAE may be formed, e.g. in the uterus, by a more......The present review focuses on the relationship between formation of N-acylethanolamine phospholipids (NAPEs) and N-acyletransferase (NAEs) catalyzed by N-acyltranferase and NAPE-hydrolyzing phospholipase D, respectively, and cell injury in tissues like brain, heart, and testis. A number...

  10. Antibodies to Phospholipids and Liposomes: Binding of Antibodies to Cells

    Science.gov (United States)

    1987-01-01

    LIPOSOMES: BINDING OF ANTIBODIES TO CELLS 12. PERSONAL AUTHOR(S) W.E. FOGLER , G. M. SWARTZ, AND C.R. ALVING 13a TYPE OF REPORT 13b. TIME COVERED 14. DATE...Elsevier BBA 73693 Antibodies to phospholipids and liposomes: binding of antibodies to cells William E. Fogler *, Glenn M. Swartz, Jr. and Carl R. Alving...Immunol. 21. Research Associateship from the U.S. National 12863-86812Hall. T. and Esser, K. (1984) 3. Immunol. 132. 2059-2063 Research Council. 13 Fogler

  11. Lysophosphatidic acid as a phospholipid mediator: pathways of synthesis.

    Science.gov (United States)

    Gaits, F; Fourcade, O; Le Balle, F; Gueguen, G; Gaigé, B; Gassama-Diagne, A; Fauvel, J; Salles, J P; Mauco, G; Simon, M F; Chap, H

    1997-06-23

    From very recent studies, including molecular cloning of cDNA coding for membrane receptors, lysophosphatidic acid (LPA) reached the status of a novel phospholipid mediator with various biological activities. Another strong argument supporting this view was the discovery that LPA is secreted from activated platelets, resulting in its appearance in serum upon blood coagulation. The metabolic pathways as well as the enzymes responsible for LPA production are poorly characterized. However, a survey of literature data indicates some interesting issues which might be used as the basis for further molecular characterization of phospholipases A able to degrade phosphatidic acid.

  12. Directional Self-assembly in Archaerhodopsin-Reconstituted Phospholipid Liposomes

    Institute of Scientific and Technical Information of China (English)

    吴佳; 黄力; 刘坚; 明明; 李庆国; 丁建东

    2005-01-01

    This paper reports, for the first time, that Archaerhodopsin-4 (AR4) could be reconstituted into phospholipid liposomes by self-assembly. AR4 is a new membrane protein isolated from halobacteria H.sp. xz515 in a salt lake of Tibet, China. This is a bacteriorhodopsin (bR) like protein, function as a light-driven proton pump. Experimental measurements verified that similar to bR, AR not only remains its biological activity in pmteoliposome, but also keeps a preferred orientation in self-assembly.

  13. Kinetics of the Bicelle to Lamellae Transition in Phospholipid Mixtures

    Science.gov (United States)

    Wang, Howard; Nieh, Mu-Ping; Hobbie, Erik K.; Glinka, Charles J.; Katsaras, John

    2002-03-01

    The kinetics of the bicelle to lamellae transition in phospholipid mixtures of DMPC/DHPC is investigated using time-resolved small-angle neutron scattering. The data suggest that ordering in these mixtures is a multi-stage process, initiated by the coalescence of bicelles into stacked membrane layers, and limited at late time by the coarsening and swelling of stacks and pinning due to defects. The time evolution of the ordering process is quantified via structural scaling of the non-equilibrium structure factor.

  14. Phospholipid bilayer formation at a bare Si surface

    DEFF Research Database (Denmark)

    Gutberlet, T.; Steitz, R.; Fragneto, G.;

    2004-01-01

    Neutron reflectivity was applied to monitor in situ the adsorption of small unilamellar phospholipid vesicles on a solid bare hydrophilic Si interface. The obtained reflectivity curves are consistent with the rupture and fusion model for the adsorption of phosphatidylcholine vesicles to solid...... interfaces. The results show details of the adsorbed bilayer system at ångström resolution and indicate the presence of a thin ∼6 Å thick water leaflet that separates the bilayer from the Si surface. The resolved structural details provide the basis for further investigation of processes such as adsorption...

  15. Priming and turnover of soil microbial biomass C and N

    Science.gov (United States)

    Voroney, Paul; Paul, Eldor

    2015-04-01

    Priming is the altered rate of mineralization of native soil organic matter (SOM) induced by an organic substrate and, depending on the nature of the amendment, can be either positive or negative. Coupled with the use of tracer (14C, 13C, 15N) techniques, measurements of the rates of CO2 evolution and organic N mineralization are typically used to assess priming effects. In this study priming was also assessed from measurements of soil microbial biomass. Soil was amended with 14C-glucose and 15N-nitrate and incubated for 42 d during which unlabelled and labelled microbial biomass C and N were measured using the chloroform-incubation method. All of the 14C-glucose was metabolized within 24-30 h at a C-use efficiency of ~60%, and resulted in a labelled biomass C:N of 9. After this period of rapid microbial growth, labelled microbial biomass C decayed at a rate of 19.3 x 10-3 d-1. Unlabelled microbial biomass C in the amended treatment decayed at 8.6 x 10-3 d-1 whereas in the unamended soil microbial biomass C decayed at half this rate (4.9 x 10-3 d-1). These data suggest that ~25% of the native microbial biomass C responded to the addition of glucose-C and when it was depleted the newly formed microbial biomass, comprised of both labelled and unlabelled- C, collapsed and subsequently was mineralized. The period of rapid microbial biomass decay coincided with an increased evolution of soil (unlabelled) CO2 and accumulation of (unlabelled) mineral N compared to that in the unamended soil. Thus, the apparent priming of soil C and N following addition of glucose can be attributed to biological recycling and increased turnover of native microbial biomass C and N. There was no evidence of priming of native soil organic matter during the first 21 days of the incubation.

  16. Myofibrillar protein turnover: the proteasome and the calpains.

    Science.gov (United States)

    Goll, D E; Neti, G; Mares, S W; Thompson, V F

    2008-04-01

    Metabolic turnover of myofibrillar proteins in skeletal muscle requires that, before being degraded to AA, myofibrillar proteins be removed from the myofibril without disrupting the ability of the myofibril to contract and develop tension. Skeletal muscle contains 4 proteolytic systems in amounts such that they could be involved in metabolic protein turnover: 1) the lysosomal system, 2) the caspase system, 3) the calpain system, and 4) the proteasome. The catheptic proteases in lysosomes are not active at the neutral pH of the cell cytoplasm, so myofibrillar proteins would have to be degraded inside lysosomes if the lysosomal system were involved. Lysosomes could not engulf a myofibril without destroying it, so the lysosomal system is not involved to a significant extent in metabolic turnover of myofibrillar proteins. The caspases are not activated until initiation of apoptosis, and, therefore, it is unlikely that the caspases are involved to a significant extent in myofibrillar protein turnover. The calpains do not degrade proteins to AA or even to small peptides and do not catalyze bulk degradation of the sarcoplasmic proteins, so they cannot be the only proteolytic system involved in myofibrillar protein turnover. Research during the past 20 yr has shown that the proteasome is responsible for 80 to 90% of total intracellular protein turnover, but the proteasome degrades peptide chains only after they have been unfolded, so that they can enter the catalytic chamber of the proteasome. Thus, although the proteasome can degrade sarcoplasmic proteins, it cannot degrade myofibrillar proteins until they have been removed from the myofibril. It remains unclear how this removal is done. The calpains degrade those proteins that are involved in keeping the myofibrillar proteins assembled in myofibrils, and it was proposed over 30 yr ago that the calpains initiated myofibrillar protein turnover by disassembling the outer layer of proteins from the myofibril and releasing

  17. Effects of phosphonium-based ionic liquids on phospholipid membranes studied by small-angle X-ray scattering.

    Science.gov (United States)

    Kontro, Inkeri; Svedström, Kirsi; Duša, Filip; Ahvenainen, Patrik; Ruokonen, Suvi-Katriina; Witos, Joanna; Wiedmer, Susanne K

    2016-12-01

    The effects of ionic liquids on model phospholipid membranes were studied by small-angle X-ray scattering, dynamic light scattering (DLS) and zeta potential measurements. Multilamellar 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine liposomes and large unilamellar vesicles composed of l-α-phosphatidylcholine (eggPC) and l-α-phosphatidylglycerol (eggPG) (80:20mol%) or eggPC, eggPG, and cholesterol (60:20:20mol%) were used as biomimicking membrane models. The effects of the phosphonium-based ionic liquids: tributylmethylphosphonium acetate, trioctylmethylphosphonium acetate, tributyl(tetradecyl)-phosphonium acetate, and tributyl(tetradecyl)-phosphonium chloride, were compared to those of 1-ethyl-3-methyl-imidazolium acetate. With multilamellar vesicles, the ionic liquids that did not disrupt liposomes decreased the lamellar spacing as a function of concentration. The magnitude of the effect depended on concentration for all studied ionic liquids. Using large unilamellar vesicles, first a slight decrease in the vesicle size, then aggregation of vesicles was observed by DLS for increasing ionic liquid concentrations. At concentrations just below those that caused aggregation of liposomes, large unilamellar vesicles were coated by ionic liquid cations, evidenced by a change in their zeta potential. The ability of phosphonium-based ionic liquids to affect liposomes is related to the length of the hydrocarbon chains in the cation. Generally, the ability of ionic liquids to disrupt liposomes goes hand in hand with inducing disorder in the phospholipid membrane. However, trioctylmethylphosphonium acetate selectively extracted and induced a well-ordered lamellar structure in phospholipids from disrupted cholesterol-containing large unilamellar vesicles. This kind of effect was not seen with any other combination of ionic liquids and liposomes.

  18. Effect of temperature, water content and free fatty acid on reverse micelle formation of phospholipids in vegetable oil.

    Science.gov (United States)

    Lehtinen, Olli-Pekka; Nugroho, Robertus Wahyu N; Lehtimaa, Tuula; Vierros, Sampsa; Hiekkataipale, Panu; Ruokolainen, Janne; Sammalkorpi, Maria; Österberg, Monika

    2017-09-22

    The self-assembly of phospholipids in oil, specifically lecithin in rapeseed oil, was investigated by combining experimental and computational methods The influence of temperature, water, and free fatty acids on the onset of lecithin aggregation in the rapeseed oil was determined using the 7,7,8,8 -tetracyanoquinodimethane dye (TCNQ) solubilization method and the size and shape of the self-assembled lecithin structures were investigated by small-angle X-ray scattering and cryogenic transmission electron microscopy. In the absence of excess water in the system (0.03wt-% water in oil), stable cylindrical lecithin reverse micelles were observed above the critical micelle concentration (CMC). Comparing the aggregation response in room temperature and at 70°C revealed that CMC decreased with increasing temperature. Furthermore, already a modest amount of added water (0.3wt-% water in oil) was sufficient to induce the formation of lamellar lecithin structures, that phase separated from the oil. In low water content, oleic acid suppressed the formation of lecithin reverse micelles whereas in the presence of more water, the oleic acid stabilized the reverse micelles. Consequently, more water was needed to induce phase separation in the presence of oleic acid. Molecular dynamics simulations indicated that the stabilizing effect of oleic acid resulted from oleic acid enhancing phospholipid solubilization in the oil by forming a solvating shell around the phosphate head group. The findings showed that the response of the mixed surfactant system is a delicate interplay of the different components and variables. The significance of the observations is that multiple parameters need to be controlled for desired system response, for example towards vegetable oil purification or phospholipid based microemulsions. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Turnover of recently assimilated carbon in arctic bryophytes.

    Science.gov (United States)

    Street, L E; Subke, J A; Sommerkorn, M; Heinemeyer, A; Williams, M

    2011-10-01

    Carbon (C) allocation and turnover in arctic bryophytes is largely unknown, but their response to climatic change has potentially significant impacts on arctic ecosystem C budgets. Using a combination of pulse-chase experiments and a newly developed model of C turnover in bryophytes, we show significant differences in C turnover between two contrasting arctic moss species (Polytrichum piliferum and Sphagnum fuscum). (13)C abundance in moss tissues (measured up to 1 year) and respired CO(2) (traced over 5 days) were used to parameterise the bryophyte C model with four pools representing labile and structural C in photosynthetic and stem tissue. The model was optimised using an Ensemble Kalman Filter to ensure a focus on estimating the confidence intervals (CI) on model parameters and outputs. The ratio of aboveground NPP:GPP in Polytrichum piliferum was 23% (CI 9-35%), with an average turnover time of 1.7 days (CI 1.1-2.5 days). The aboveground NPP:GPP ratio in Sphagnum fuscum was 43% (CI 19-65%) with an average turnover time of 3.1 days (CI 1.6-6.1 days). These results are the first to show differences in C partitioning between arctic bryophyte species in situ and highlight the importance of modelling C dynamics of this group separately from vascular plants for a realistic representation of vegetation in arctic C models.

  20. [Cost of nursing turnover in a Teaching Hospital].

    Science.gov (United States)

    Ruiz, Paula Buck de Oliveira; Perroca, Marcia Galan; Jericó, Marli de Carvalho

    2016-02-01

    To map the sub processes related to turnover of nursing staff and to investigate and measure the nursing turnover cost. This is a descriptive-exploratory study, classified as case study, conducted in a teaching hospital in the southeastern, Brazil, in the period from May to November 2013. The population was composed by the nursing staff, using Nursing Turnover Cost Calculation Methodology. The total cost of turnover was R$314.605,62, and ranged from R$2.221,42 to R$3.073,23 per employee. The costs of pre-hire totaled R$101.004,60 (32,1%), and the hiring process consumed R$92.743,60 (91.8%) The costs of post-hire totaled R$213.601,02 (67,9%), for the sub process decreased productivity, R$199.982,40 (93.6%). The study identified the importance of managing the cost of staff turnover and the financial impact of the cost of the employee termination, which represented three times the average salary of the nursing staff.

  1. Cost of nursing turnover in a Teaching Hospital

    Directory of Open Access Journals (Sweden)

    Paula Buck de Oliveira Ruiz

    2016-02-01

    Full Text Available Abstract OBJECTIVE To map the sub processes related to turnover of nursing staff and to investigate and measure the nursing turnover cost. METHOD This is a descriptive-exploratory study, classified as case study, conducted in a teaching hospital in the southeastern, Brazil, in the period from May to November 2013. The population was composed by the nursing staff, using Nursing Turnover Cost Calculation Methodology. RESULTS The total cost of turnover was R$314.605,62, and ranged from R$2.221,42 to R$3.073,23 per employee. The costs of pre-hire totaled R$101.004,60 (32,1%, and the hiring process consumed R$92.743,60 (91.8% The costs of post-hire totaled R$213.601,02 (67,9%, for the sub process decreased productivity, R$199.982,40 (93.6%. CONCLUSION The study identified the importance of managing the cost of staff turnover and the financial impact of the cost of the employee termination, which represented three times the average salary of the nursing staff.

  2. Deposition and aggregation of aspirin molecules on a phospholipid bilayer pattern.

    Science.gov (United States)

    Mao, Guangzhao; Chen, Dongzhong; Handa, Hitesh; Dong, Wenfei; Kurth, Dirk G; Möhwald, Helmuth

    2005-01-18

    Aspirin and 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine (DMPE) are deposited from their alcoholic mixed solution onto highly oriented pyrolytic graphite (HOPG) by spin coating. The film structure and morphology are characterized by atomic force microscopy (AFM). The barely soluble DMPE forms a highly oriented stripe phase as a result of its one-dimensional epitaxy with the HOPG lattice. The bilayer stripe pattern exposes the cross section of the lipid bilayer lamellae and enables the direct visualization of the molecular interactions of drug or biological molecules with either the hydrophobic or the hydrophilic part of the phospholipid bilayer. The bilayer pattern affects the aspirin molecular deposition and aggregation. AFM shows that the aspirin molecules prefer to deposit and aggregate along the aliphatic interior part of the bilayer pattern, giving rise to parallel dimer rods in registry with the underlying pattern. The nonpolar interactions between aspirin and the phospholipid bilayer are consistent with the lipophilic nature of aspirin. The bilayer pattern not only stabilizes the rodlike aggregate structure of aspirin at low aspirin concentration but also inhibits crystallization of aspirin at high aspirin concentration. Molecular models show that the width of the DMPE aliphatic chain interior can accommodate no more than two aspirin dimers. The bilayer confinement may prevent aspirin from reaching its critical nucleus size. This study illustrates a general method to induce a metastable or amorphous form of an active pharmaceutical ingredient (API) by chemical confinement under high undercooling conditions. Metastable and amorphous solids often display better solubility and bioavailability than the stable crystalline form of the API.

  3. Milk-based phospholipids increase morning cortisol availability and improve memory in chronically stressed men.

    Science.gov (United States)

    Schubert, Melanie; Contreras, Carina; Franz, Nadin; Hellhammer, Juliane

    2011-06-01

    Phospholipids (PLs) have been shown to dampen the activity and reactivity of the hypothalamic-pituitary-adrenal axis (HPAA). To further investigate stress protective effects of PL, 75 chronically stressed men aged 30 to 51 years were enrolled in a randomized and placebo-controlled trial. The subjects received a bovine milk drink with either 0.5% PL, 1% PL, or a placebo for 42 days to test the hypothesis that supplementation with specific phospholipids would normalize the cortisol response of the HPAA. For determining HPAA activity, the cortisol awakening response was studied before and after treatment. In addition, participants were exposed to an acute stressor, the Trier Social Stress Test, to assess treatment effects on stress reactivity and stress-related memory impairment. After receiving PL-enriched milk, both PL groups showed a delayed decline from peak levels in morning salivary cortisol, suggesting a prolonged availability of free cortisol. Treatment with 0.5% PL additionally resulted in a stronger increase of cortisol after awakening, whereas no such differences could be observed in the 1% PL group and the placebo group, respectively. The acute stress response did not significantly differ among placebo and PL groups. An exploratory data analysis further revealed that elderly participants receiving the higher PL dosage had a significant better memory performance after the Trier Social Stress Test as compared with elderly participants from the placebo and low-PL dosage group; no such difference was observed at baseline. Our results suggest that PL may increase the availability of cortisol in chronically stressed men and may attenuate stress-induced memory impairments. Results of the present study are discussed within the context of previous research and current state of knowledge. Copyright © 2011 Elsevier Inc. All rights reserved.

  4. Developmental changes in polyunsaturated fetal plasma phospholipids and feto-maternal plasma phospholipid ratios and their association with bronchopulmonary dysplasia.

    Science.gov (United States)

    Bernhard, Wolfgang; Raith, Marco; Koch, Vera; Maas, Christoph; Abele, Harald; Poets, Christian F; Franz, Axel R

    2016-10-01

    Docosahexaenoic (C22:6) and arachidonic acid (C20:4) are long-chain polyunsaturated fatty acids (LC-PUFA), essential to fetal development, and preferentially transported by plasma phospholipids. To characterize fetal and maternal plasma phospholipid changes during gestation, and to investigate whether LC-PUFA phospholipid profiles are associated with bronchopulmonary dysplasia (BPD). Cord plasma and parturient serum from N = 108 pregnancies [24-42 week postmenstrual age (PMA)] were collected. Phosphatidylcholine (PC) and phosphatidylethanolamine (PE) were analyzed with tandem mass spectrometry. PMA-associated changes were quantified, and break point analyses served to describe nonlinear changes during gestation. PC and PE were lower in cord than in parturient samples. In parturients, PC decreased until 33 week PMA, but then re-increased, whereas in cord plasma, concentrations linearly decreased. Fetal PC and PC sub-group values correlated with maternal values. C20:4-PC was twofold higher in cord than in maternal samples throughout gestation. C22:6-PC values, however, exceeded maternal values only beyond 33 week PMA. Consequently, early preterm C20:4-PC-to-C22:6-PC ratio largely exceeded term infant values. In infants born before 28 week PMA, a low C20:4-PC-to-C22:6-PC ratio was associated with BPD severity. Fetal plasma LC-PUFA-PC composition correlates with maternal values. Fetal C20:4-PC exceeds maternal values throughout gestation, whereas C22:6-PC exceeds maternal values only beyond 33 week PMA, resulting in a low fetal C20:4-PC/C22:6-PC ratio only toward end gestation. A low C20:4-PC/C22:6-PC ratio before 28 week PMA is associated with BPD severity. These data point to a concept of PMA-adjusted ARA and DHA supplementation and, potentially, cord plasma phospholipid analysis for BPD prediction.

  5. Reduced Bone Turnover in Mice Lacking the P2Y13 Receptor of ADP

    Science.gov (United States)

    Wang, Ning; Robaye, Bernard; Agrawal, Ankita; Skerry, Timothy M.; Boeynaems, Jean-Marie

    2012-01-01

    Osteoporosis is a condition of excessive and uncoupled bone turnover, in which osteoclastic resorption exceeds osteoblastic bone formation, resulting in an overall net bone loss, bone fragility, and morbidity. Although numerous treatments have been developed to inhibit bone loss by blocking osteoclastic bone resorption, understanding of the mechanisms behind bone loss is incomplete. The purinergic signaling system is emerging to be a pivotal regulator of bone homeostasis, and extracellular ADP has previously been shown to be a powerful osteolytic agent in vitro. We report here that deletion of the P2Y13 receptor, a G protein-coupled receptor for extracellular ADP, leads to a 40% reduction in trabecular bone mass, 50% reduction in osteoblast and osteoclast numbers in vivo, as well as activity in vitro, and an overall 50% reduction in the rate of bone remodeling in mice in vivo. Down-regulation of RhoA/ROCK I signaling and a reduced ratio of receptor activator of nuclear factor κB ligand/osteoprotegerin observed in osteoblasts from P2Y13R−/− mice might explain this bone phenotype. Furthermore, because one of the main causes of osteoporosis in older women is lack of estrogen, we examined the effect of ovariectomy of the P2Y13R−/− mice and found them to be protected from ovariectomy-induced bone loss by up to 65%. These data confirm a role of purinergic ADP signaling in the skeleton, whereby deletion of the P2Y13 receptor leads to reduced bone turnover rates, which provide a protective advantage in conditions of accelerated bone turnover such as oestrogen deficiency-induced osteoporosis. PMID:22108801

  6. Presenilin 1 regulates epidermal growth factor receptor turnover and signaling in the endosomal-lysosomal pathway.

    Science.gov (United States)

    Repetto, Emanuela; Yoon, Il-Sang; Zheng, Hui; Kang, David E

    2007-10-26

    Mutations in the gene encoding presenilin 1 (PS1) cause the most aggressive form of early-onset familial Alzheimer disease. In addition to its well established role in Abeta production and Notch proteolysis, PS1 has been shown to mediate other physiological activities, such as regulation of the Wnt/beta-catenin signaling pathway, modulation of phosphatidylinositol 3-kinase/Akt and MEK/ERK signaling, and trafficking of select membrane proteins and/or intracellular vesicles. In this study, we present evidence that PS1 is a critical regulator of a key signaling receptor tyrosine kinase, epidermal growth factor receptor (EGFR). Specifically, EGFR levels were robustly increased in fibroblasts deficient in both PS1 and PS2 (PS(-/-)) due to delayed turnover of EGFR protein. Stable transfection of wild-type PS1 but not PS2 corrected EGFR to levels comparable to PS(+/+) cells, while FAD PS1 mutations showed partial loss of activity. The C-terminal fragment of PS1 was sufficient to fully reduce EGFR levels. In addition, the rapid ligand-induced degradation of EGFR was markedly delayed in PS(-/-) cells, resulting in prolonged signal activation. Despite the defective turnover of EGFR, ligand-induced autophosphorylation, ubiquitination, and endocytosis of EGFR were not affected by the lack of PS1. Instead, the trafficking of EGFR from early endosomes to lysosomes was severely delayed by PS1 deficiency. Elevation of EGFR was also seen in brains of adult mice conditionally ablated in PS1 and in skin tumors associated with the loss of PS1. These findings demonstrate a critical role of PS1 in the trafficking and turnover of EGFR and suggest potential pathogenic effects of elevated EGFR as well as perturbed endosomal-lysosomal trafficking in cell cycle control and Alzheimer disease.

  7. Analysis of Quil A-phospholipid mixtures using drift spectroscopy.

    Science.gov (United States)

    Demana, Patrick H; Davies, Nigel M; Hook, Sarah; Rades, Thomas

    2007-09-05

    The aim of this study was to investigate molecular interactions between Quil A and phosphatidylcholine in the solid state using diffuse reflectance infrared Fourier-transform spectroscopy (DRIFTS). Analysis of the interactions was characterized on the different regions of phosphatidylcholine: hydrophobic chain, interfacial and headgroup regions. The spectra of the hydrocarbon region of phosphatidylcholine alone compared to that for the binary mixture of Quil A and phosphatidylcholine were similar. These findings suggest that Quil A did not cause conformational disorder of the fatty acyl chains of the phospholipid. In contrast, a shift in the wavenumber of the choline group and a broad band in this moiety indicate a modification of the phospholipid in the headgroup region due to interaction between Quil A and phosphatidylcholine. These results suggest possibly ionic interactions between the negatively charged glucuronic acid moiety of the Quil A molecule with the positively charged choline group. The findings could also be the result of conformational changes in the choline group because of the intercalation of sugar moieties in Quil A between the choline and phosphate groups due to hydrogen bonding. Shift of wavenumbers to lower values on the carbonyl group was observed suggesting hydrogen bonding between Quil A and phosphatidylcholine. The difference in degrees of wavenumber shift (choline>phosphate>carbonyl group) and observed broad bands indicated that Quil A preferentially interacted with phosphatidylcholine on the hydrophilic headgroup. Cholesterol influenced such interactions at relatively high concentration (60%, w/w).

  8. Spontaneous structural transition in phospholipid-inspired aromatic phosphopeptide nanostructures.

    Science.gov (United States)

    Pellach, Michal; Atsmon-Raz, Yoav; Simonovsky, Eyal; Gottlieb, Hugo; Jacoby, Guy; Beck, Roy; Adler-Abramovich, Lihi; Miller, Yifat; Gazit, Ehud

    2015-01-01

    Phospholipid membranes could be considered a prime example of the ability of nature to produce complex yet ordered structures, by spontaneous and efficient self-assembly. Inspired by the unique properties and architecture of phospholipids, we designed simple amphiphilic decapeptides, intended to fold in the center of the peptide sequence, with a phosphorylated serine "head" located within a central turn segment, and two hydrophobic "tails". The molecular design also included the integration of the diphenylalanine motif, previously shown to facilitate self-assembly and increase nanostructure stability. Secondary structure analysis of the peptides indeed indicated the presence of stabilized conformations in solution, with a central turn connecting two hydrophobic "tails", and interactions between the hydrophobic strands. The mechanisms of assembly into supramolecular structures involved structural transitions between different morphologies, which occurred over several hours, leading to the formation of distinctive nanostructures, including half-elliptical nanosheets and curved tapes. The phosphopeptide building blocks appear to self-assemble via a particular combination of aromatic, hydrophobic and ionic interactions, as well as hydrogen bonding, as demonstrated by proposed constructed simulated models of the peptides and self-assembled nanostructures. Molecular dynamics simulations also gave insight into mechanisms of structural transitions of the nanostructures at a molecular level. Because of the biocompatibility of peptides, the phosphopeptide assemblies allow for expansion of the library of biomolecular nanostructures available for future design and application of biomedical devices.

  9. Phospholipid Polymer Biointerfaces for Lab-on-a-Chip Devices.

    Science.gov (United States)

    Xu, Yan; Takai, Madoka; Ishihara, Kazuhiko

    2010-06-01

    This review summarizes recent achievements and progress in the development of various functional 2-methacryloyloxyethyl phosphorylcholine (MPC) polymer biointerfaces for lab-on-a-chip devices and applications. As phospholipid polymers, MPC polymers can form cell-membrane-like surfaces by surface chemistry and physics and thereby provide biointerfaces capable of suppressing protein adsorption and many subsequent biological responses. In order to enable application to microfluidic devices, a number of MPC polymers with diverse functions have been specially designed and synthesized by incorporating functional units such as charge and active ester for generating the microfluidic flow and conjugating biomolecules, respectively. Furthermore, these polymers were incorporated with silane or hydrophobic moiety to construct stable interfaces on various substrate materials such as glass, quartz, poly(methyl methacrylate), and poly(dimethylsiloxane), via a silane-coupling reaction or hydrophobic interactions. The basic interfacial properties of these interfaces have been characterized from multiple aspects of chemistry, physics, and biology, and the suppression of nonspecific bioadsorption and control of microfluidic flow have been successfully achieved using these biointerfaces on a chip. Further, many chip-based biomedical applications such as immunoassays and DNA separation have been accomplished by integrating these biointerfaces on a chip. Therefore, functional phospholipid polymer interfaces are promising and useful for application to lab-on-a-chip devices in biomedicine.

  10. Cell separation in microcanal coated with electrically charged phospholipid polymers.

    Science.gov (United States)

    Ito, Tomomi; Iwasaki, Yasuhiko; Narita, Tadashi; Akiyoshi, Kazunari; Ishihara, Kazuhiko

    2005-03-25

    To separate the cell population in whole blood using microcanal, the surface was covered with a polyion complex (PIC) composed of electrically charged phospholipid polymers. The phospholipids polymers were prepared by the polymerization of 2-methacryloyloxyethyl phosphorylcholine (MPC) and n-butyl methacrylate with 3-(methacryloyloxypropyl)-trimethyl ammonium iodide as the cationic unit or potassium 3-methacryloyloxypropyl sulfonate as the anionic unit. The PIC was formed at the solid-liquid interface, that is, first, the cationic polymer was coated on the substrate and an aqueous solution containing the anionic polymer with different concentrations was applied to the polymer-coated substrate. The formation of the PIC was followed using a quartz crystal microbalance (QCM), and the PIC surfaces were analyzed by both zeta-potential measurement and X-ray photoelectron spectroscopic measurement. The surface electrical potential on the PIC was controllable from +40 to -40 mV by increasing the amount of the adsorbed anionic polymer. The PIC surface was prepared in microcanal. The surface electrical potential was sequentially changed. When the whole blood was introduced into the microcanal, the cells adhered on the positively charged surface, but could not adhere to the negatively charged surface. Even when the cells adhere to the surface, the morphology of cells was maintained. This is due to MPC units at the surface, which show a good biocompatibility. These results indicated that the change in the surface electrical potential will be a useful method to separate the cells from whole blood.

  11. Characterization of phospholipid mixed micelles by translational diffusion.

    Science.gov (United States)

    Chou, James J; Baber, James L; Bax, Ad

    2004-07-01

    The concentration dependence of the translational self diffusion rate, D (s), has been measured for a range of micelle and mixed micelle systems. Use of bipolar gradient pulse pairs in the longitudinal eddy current delay experiment minimizes NOE attenuation and is found critical for optimizing sensitivity of the translational diffusion measurement of macromolecules and aggregates. For low volume fractions Phi (Phi\\\\ le 15% v/v) of the micelles, experimental measurement of the concentration dependence, combined with use of the D (s)= D (o)(1-3.2lambdaPhi) relationship, yields the hydrodynamic volume. For proteins, the hydrodynamic volume, derived from D (s) at infinitely dilute concentration, is found to be about 2.6 times the unhydrated molecular volume. Using the data collected for hen egg white lysozyme as a reference, diffusion data for dihexanoyl phosphatidylcholine (DHPC) micelles indicate approximately 27 molecules per micelle, and a critical micelle concentration of 14 mM. Differences in translational diffusion rates for detergent and long chain phospholipids in mixed micelles are attributed to rapid exchange between free and micelle-bound detergent. This difference permits determination of the free detergent concentration, which, for a high detergent to long chain phospholipid molar ratio, is found to depend strongly on this ratio. The hydrodynamic volume of DHPC/POPC bicelles, loaded with an M2 channel peptide homolog, derived from translational diffusion, predicts a rotational correlation time that slightly exceeds the value obtained from peptide (15)N relaxation data.

  12. Characterization of Phospholipid Mixed Micelles by Translational Diffusion

    Energy Technology Data Exchange (ETDEWEB)

    Chou, James J. [Harvard Medical School, Department of Biological Chemistry and Molecular Pharmacology (United States); Baber, James L.; Bax, Ad [National Institutes of Health, Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases (United States)], E-mail: bax@nih.gov

    2004-07-15

    The concentration dependence of the translational self diffusion rate, D{sub s}, has been measured for a range of micelle and mixed micelle systems. Use of bipolar gradient pulse pairs in the longitudinal eddy current delay experiment minimizes NOE attenuation and is found critical for optimizing sensitivity of the translational diffusion measurement of macromolecules and aggregates. For low volume fractions {phi} ({phi} {<=} 15% v/v) of the micelles, experimental measurement of the concentration dependence, combined with use of the D{sub s}=D{sub o}(1-3.2{lambda}{phi}) relationship, yields the hydrodynamic volume. For proteins, the hydrodynamic volume, derived from D{sub s} at infinitely dilute concentration, is found to be about 2.6 times the unhydrated molecular volume. Using the data collected for hen egg white lysozyme as a reference, diffusion data for dihexanoyl phosphatidylcholine (DHPC) micelles indicate approximately 27 molecules per micelle, and a critical micelle concentration of 14 mM. Differences in translational diffusion rates for detergent and long chain phospholipids in mixed micelles are attributed to rapid exchange between free and micelle-bound detergent. This difference permits determination of the free detergent concentration, which, for a high detergent to long chain phospholipid molar ratio, is found to depend strongly on this ratio. The hydrodynamic volume of DHPC/POPC bicelles, loaded with an M2 channel peptide homolog, derived from translational diffusion, predicts a rotational correlation time that slightly exceeds the value obtained from peptide {sup 15}N relaxation data.

  13. Phospholipid homeostasis and lipotoxic cardiomyopathy: a matter of balance.

    Science.gov (United States)

    Lim, Hui-Ying; Bodmer, Rolf

    2011-01-01

    Obesity has reached pandemic proportions globally and is often associated with lipotoxic heart diseases. In the obese state, caloric surplus is accommodated in the adipocytes as triglycerides. As the storage capacity of adipocytes is exceeded or malfunctioning, lipids begin to infiltrate and accumulate in non-adipose tissues, including the myocardium of the heart, leading to organ dysfunction. While the disruption of caloric homeostasis has been widely viewed as a principal mechanism in contributing to peripheral tissue steatosis and lipotoxicity, our recent studies in Drosophila have led to the novel finding that deregulation of phospholipid homeostasis may also significantly contribute to the pathogenesis of lipotoxic cardiomyopathy. Fly mutants that bear perturbations in phosphatidylethanolamine (PE) biosynthesis, such as the easily-shocked (eas) mutants defective in ethanolamine kinase, incurred aberrant activation of the sterol regulatory element binding protein (SREBP) pathway, thereby causing chronic lipogenesis and cardiac steatosis that culminates in the development of lipotoxic cardiomyopathy. Here, we describe the potential relationship between SREBP and other eas-associated phenotypes, such as neuronal excitability defects. We will further discuss the additional implications presented by our work toward the effects of altered lipid metabolism on cellular growth and/or proliferation in response to defective phospholipid homeostasis.

  14. Inositol depletion restores vesicle transport in yeast phospholipid flippase mutants.

    Science.gov (United States)

    Yamagami, Kanako; Yamamoto, Takaharu; Sakai, Shota; Mioka, Tetsuo; Sano, Takamitsu; Igarashi, Yasuyuki; Tanaka, Kazuma

    2015-01-01

    In eukaryotic cells, type 4 P-type ATPases function as phospholipid flippases, which translocate phospholipids from the exoplasmic leaflet to the cytoplasmic leaflet of the lipid bilayer. Flippases function in the formation of transport vesicles, but the mechanism remains unknown. Here, we isolate an arrestin-related trafficking adaptor, ART5, as a multicopy suppressor of the growth and endocytic recycling defects of flippase mutants in budding yeast. Consistent with a previous report that Art5p downregulates the inositol transporter Itr1p by endocytosis, we found that flippase mutations were also suppressed by the disruption of ITR1, as well as by depletion of inositol from the culture medium. Interestingly, inositol depletion suppressed the defects in all five flippase mutants. Inositol depletion also partially restored the formation of secretory vesicles in a flippase mutant. Inositol depletion caused changes in lipid composition, including a decrease in phosphatidylinositol and an increase in phosphatidylserine. A reduction in phosphatidylinositol levels caused by partially depleting the phosphatidylinositol synthase Pis1p also suppressed a flippase mutation. These results suggest that inositol depletion changes the lipid composition of the endosomal/TGN membranes, which results in vesicle formation from these membranes in the absence of flippases.

  15. [Plasma lipoproteins as drug carriers. Effect of phospholipid formulations].

    Science.gov (United States)

    Torkhovskaia, T I; Ipatova, O M; Medvedeva, N V; Ivanov, V S; Ivanova, L I

    2010-01-01

    The extensive development of nanotechnologies in the last two decades has brought about new understanding of plasma lipoproteins (LP) as natural drug nanocarriers that escape interaction with immune and reticuloendothelial systems. Drugs bound to LP (especially LDL) can more actively penetrate into cells of many cancer and inflammation tissues with enhanced expression or/and dysregulation of B,E receptors or possibly scavenger SR-BI receptors. Relevant studies are focused on the development of new dosage forms by conjugating lipophilic drugs either with isolated plasma LP or with their model formulations, such as nanoemulsions, mimetics, lipid nanospheres, etc. Some authors include in these particles serum or recombinant apoproteins, peptides, and modified polymer products. As shown recently, protein-free lipid nanoemulsions in plasma take up free apoA and apoE. Complexes with various LP also form after direct administration of lypophilic drugs into blood especially those enclosed in phospholipid formulations, e.g. liposomes. Results of evaluation of some lipophilic dugs (mainly cytostatics, amphotericin B, cyclosporine A, etc.) are discussed. Original data are presented on the influence of phospholipid formulations on the distribution of doxorubicin and indomethacin between LP classes after in vitro incubation in plasma. On the whole, the review illustrates the importance of research on LP and phospholi pid forms as drug nanocarriers to be used to enhance effect of therapy.

  16. Cationic Polyene Phospholipids as DNA Carriers for Ocular Gene Therapy

    Directory of Open Access Journals (Sweden)

    Susana Machado

    2014-01-01

    Full Text Available Recent success in the treatment of congenital blindness demonstrates the potential of ocular gene therapy as a therapeutic approach. The eye is a good target due to its small size, minimal diffusion of therapeutic agent to the systemic circulation, and low immune and inflammatory responses. Currently, most approaches are based on viral vectors, but efforts continue towards the synthesis and evaluation of new nonviral carriers to improve nucleic acid delivery. Our objective is to evaluate the efficiency of novel cationic retinoic and carotenoic glycol phospholipids, designated C20-18, C20-20, and C30-20, to deliver DNA to human retinal pigmented epithelium (RPE cells. Liposomes were produced by solvent evaporation of ethanolic mixtures of the polyene compounds and coformulated with 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE or cholesterol (Chol. Addition of DNA to the liposomes formed lipoplexes, which were characterized for binding, size, biocompatibility, and transgene efficiency. Lipoplex formulations of suitable size and biocompatibility were assayed for DNA delivery, both qualitatively and quantitatively, using RPE cells and a GFP-encoding plasmid. The retinoic lipoplex formulation with DOPE revealed a transfection efficiency comparable to the known lipid references 3β-[N-(N′,N′-dimethylaminoethane-carbamoyl]-cholesterol (DC-Chol and 1,2-dioleoyl-sn-glycero-3-ethylphosphocholine (EPC and GeneJuice. The results demonstrate that cationic polyene phospholipids have potential as DNA carriers for ocular gene therapy.

  17. Firm-level innovation activity, employee turnover and HRM practices

    DEFF Research Database (Denmark)

    Eriksson, Tor; Qin, Zhihua; Wang, Wenjing

    2014-01-01

    This paper examines the relationship between employee turnover, HRM practices and innovation in Chinese firms in five high technology sectors. We estimate hurdle negative binomial models for count data on survey data allowing for analyses of the extensive as well as intensive margins of firms....... Innovating firms are more likely to have adopted high performance HRM practices, and the impact of employee turnover varies with the number of HRM practices implemented by the firm......' innovation activities. Innovation is measured both by the number of ongoing projects and new commercialized products. The results show that higher R&D employee turnover is associated with a higher probability of being innovative, but decreases the intensity of innovation activities in innovating firms...

  18. Decay times in turnover statistics of single enzymes

    CERN Document Server

    Lindén, Martin

    2008-01-01

    The first passage times for enzymatic turnovers in non-equilibrium steady state display a statistical symmetry property related to non-equilibrium fluctuation theorems, that makes it possible to extract the chemical driving force from single molecule trajectories in non-equilibrium steady state. Below, we show that this system violates the general expectation that the number of decay constants needed to fit a first passage time distribution reflects the number of states in the escape problem. In fact, the structure of the kinetic mechanism makes half of the decay times vanish identically from the turnover time distribution. The terms that cancel out correspond to the eigenvalues of a certain sub-matrix of the master equation matrix for the first exit time problem. We discuss how these results make modeling and data analysis easier for such systems, and how the turnovers can be measured.

  19. No turnover in lens lipids for the entire human lifespan.

    Science.gov (United States)

    Hughes, Jessica R; Levchenko, Vladimir A; Blanksby, Stephen J; Mitchell, Todd W; Williams, Alan; Truscott, Roger J W

    2015-03-11

    Lipids are critical to cellular function and it is generally accepted that lipid turnover is rapid and dysregulation in turnover results in disease (Dawidowicz 1987; Phillips et al., 2009; Liu et al., 2013). In this study, we present an intriguing counter-example by demonstrating that in the center of the human ocular lens, there is no lipid turnover in fiber cells during the entire human lifespan. This discovery, combined with prior demonstration of pronounced changes in the lens lipid composition over a lifetime (Hughes et al., 2012), suggests that some lipid classes break down in the body over several decades, whereas others are stable. Such substantial changes in lens cell membranes may play a role in the genesis of age-related eye disorders. Whether long-lived lipids are present in other tissues is not yet known, but this may prove to be important in understanding the development of age-related diseases.

  20. Estimation of Employee Turnover with Competing Risks Models

    Directory of Open Access Journals (Sweden)

    Grzenda Wioletta

    2015-12-01

    Full Text Available Employee turnover accompanies every business organization, regardless of the industry and size. Nowadays, many companies struggle with problems related to the lack of sufficient information about the nature of employee turnover processes. Therefore, comprehensive analysis of these processes is necessary. This article aims to examine the turnover of employees from a big manufacturing company using competing risks models with covariates and without covariates. This technique allows to incorporate the information about the type of employment contract termination. Moreover, Cox proportional hazard model enables the researcher to analyse simultaneously multiple factors that affect employment duration. One of the major observations is that employee remuneration level differentiates most strongly the risk of job resignation.

  1. Quality of Working Life: An Antecedent to Employee Turnover Intention

    Science.gov (United States)

    Mosadeghrad, Ali Mohammad

    2013-01-01

    Background: The purpose of this study was to measure the level of quality of work life (QWL) among hospital employees in Iran. Additionally, it aimed to identify the factors that are critical to employees’ QWL. It also aimed to test a theoretical model of the relationship between employees’ QWL and their intention to leave the organization. Methods: A survey study was conducted based on a sample of 608 hospital employees using a validated questionnaire. Face, content and construct validity were conducted on the survey instrument. Results: Hospital employees reported low QWL. Employees were least satisfied with pay, benefits, job promotion, and management support. The most important predictor of QWL was management support, followed by job proud, job security and job stress. An inverse relationship was found between employees QWL and their turnover intention. Conclusion: This study empirically examined the relationships between employees’ QWL and their turnover intention. Managers can take appropriate actions to improve employees’ QWL and subsequently reduce employees’ turnover. PMID:24596835

  2. Human turnover dynamics during sleep: Statistical behavior and its modeling

    Science.gov (United States)

    Yoneyama, Mitsuru; Okuma, Yasuyuki; Utsumi, Hiroya; Terashi, Hiroo; Mitoma, Hiroshi

    2014-03-01

    Turnover is a typical intermittent body movement while asleep. Exploring its behavior may provide insights into the mechanisms and management of sleep. However, little is understood about the dynamic nature of turnover in healthy humans and how it can be modified in disease. Here we present a detailed analysis of turnover signals that are collected by accelerometry from healthy elderly subjects and age-matched patients with neurodegenerative disorders such as Parkinson's disease. In healthy subjects, the time intervals between consecutive turnover events exhibit a well-separated bimodal distribution with one mode at ⩽10 s and the other at ⩾100 s, whereas such bimodality tends to disappear in neurodegenerative patients. The discovery of bimodality and fine temporal structures (⩽10 s) is a contribution that is not revealed by conventional sleep recordings with less time resolution (≈30 s). Moreover, we estimate the scaling exponent of the interval fluctuations, which also shows a clear difference between healthy subjects and patients. We incorporate these experimental results into a computational model of human decision making. A decision is to be made at each simulation step between two choices: to keep on sleeping or to make a turnover, the selection of which is determined dynamically by comparing a pair of random numbers assigned to each choice. This decision is weighted by a single parameter that reflects the depth of sleep. The resulting simulated behavior accurately replicates many aspects of observed turnover patterns, including the appearance or disappearance of bimodality and leads to several predictions, suggesting that the depth parameter may be useful as a quantitative measure for differentiating between normal and pathological sleep. These findings have significant clinical implications and may pave the way for the development of practical sleep assessment technologies.

  3. Public schools’ characteristics and teacher turnover in Oman

    Directory of Open Access Journals (Sweden)

    Khairuddin Idris

    2013-10-01

    Full Text Available Teachers are the backbone of the educational systems and their turnover may threaten the whole educational system in any country. In Oman, teacher turnover is a neglected area of study and this article may help in shedding some light on teacher turnover phenomenon in Oman. The purpose of this study is to investigate the influence of school characteristics (e.g., school size, gender, time-shift, education type, and school location on the turnover intentions of teachers in public schools in Oman. Survey questionnaires were used to collect data from 214 public schools in Oman. 142 schools from all educational regions in Oman were participated in this study. Data analyses tools for this study were descriptive statistics such as mean and standard deviation, in addition to independents t-test and analysis of variance. The study revealed that teacher intentions to transfer to other schools are influenced by almost all the studied school characteristics. Policy makers and human resource recruiters in Ministry of Education should be aware of teachers’ preferences for certain schools to avoid teachers’ shortage in non-preferred schools. Further studies about the influence of school time-shift and teachers’ intentions to quit or transfer are needed to affirm the results in this study. This is the first study about the influence of school characteristics on teacher turnover in public schools in Oman. Thus, the value of this study stems from the uniqueness of this study which may serve as an eye opening indicator about teacher turnover in Oman.

  4. Human turnover dynamics during sleep: statistical behavior and its modeling.

    Science.gov (United States)

    Yoneyama, Mitsuru; Okuma, Yasuyuki; Utsumi, Hiroya; Terashi, Hiroo; Mitoma, Hiroshi

    2014-03-01

    Turnover is a typical intermittent body movement while asleep. Exploring its behavior may provide insights into the mechanisms and management of sleep. However, little is understood about the dynamic nature of turnover in healthy humans and how it can be modified in disease. Here we present a detailed analysis of turnover signals that are collected by accelerometry from healthy elderly subjects and age-matched patients with neurodegenerative disorders such as Parkinson's disease. In healthy subjects, the time intervals between consecutive turnover events exhibit a well-separated bimodal distribution with one mode at ⩽10 s and the other at ⩾100 s, whereas such bimodality tends to disappear in neurodegenerative patients. The discovery of bimodality and fine temporal structures (⩽10 s) is a contribution that is not revealed by conventional sleep recordings with less time resolution (≈30 s). Moreover, we estimate the scaling exponent of the interval fluctuations, which also shows a clear difference between healthy subjects and patients. We incorporate these experimental results into a computational model of human decision making. A decision is to be made at each simulation step between two choices: to keep on sleeping or to make a turnover, the selection of which is determined dynamically by comparing a pair of random numbers assigned to each choice. This decision is weighted by a single parameter that reflects the depth of sleep. The resulting simulated behavior accurately replicates many aspects of observed turnover patterns, including the appearance or disappearance of bimodality and leads to several predictions, suggesting that the depth parameter may be useful as a quantitative measure for differentiating between normal and pathological sleep. These findings have significant clinical implications and may pave the way for the development of practical sleep assessment technologies.

  5. Work climate perception and turnover intention among Korean hospital staff.

    Science.gov (United States)

    Hwang, J-I; Chang, H

    2009-03-01

    To examine the impact of work climate perception (WCP) on turnover intention among public hospital personnel in Korea. With increased competition and high staff turnover in hospitals, managers focus on human resource management. Positive work climate is considered as a strategy to retain valued staff, but previous studies have shown occupationally different relationships between turnover intention and work environment characteristics as perceived by staff. A cross-sectional questionnaire survey was conducted of employees (n = 852) in four public hospitals in Korea to gather information about WCP, intention to leave and demographics. The work climate was measured by 32 items categorized into 13 factors in five dimensions. For each occupation, logistic regression analyses were performed to determine the significant factors of WCP that influenced turnover intention. Positive WCP inversely influenced turnover intention. For all occupations, the most significant factor was 'workgroup friendliness and warmth' (OR = 0.01-0.21). For the nursing group, an additional significant factor was 'adherence to job standard' (OR = 0.63). In contrast, there were different significant factors for other hospital staff: 'workgroup esprit de corps' (OR = 0.16) and 'role clarity' (OR = 0.19) for physicians, 'adherence to job standard' (OR = 3.08) and 'role adaptation' (OR = 2.23) for paramedicals, and 'flexibility and innovation' (OR = 0.14) and 'interdepartmental cooperation' (OR = 0.19) for administrators. Nurses with perceptions of work climate emphasizing 'workgroup friendliness and warmth' and 'adherence to job standard' had lower turnover intention. Physicians, paramedicals and administrators have different WCPs. To retain qualified personnel, hospitals should focus on human relations, maintaining a consideration for occupation-specific characteristics.

  6. Nonlicensed employee turnover in a long-term care facility.

    Science.gov (United States)

    Gaddy, T; Bechtel, G A

    1995-06-01

    The purpose of this study was to analyze nonlicensed employee turnover in a long-term care facility using Maslow's hierarchy of needs as a framework. During exit interviews, a convenience sample of 34 employees completed an attitudes and beliefs survey regarding their work environment. Findings were mixed; 39.6 percent of the employees stated positive personal relationships were a strength of the organization, although 24.3 percent resigned because of personal/staff conflicts. Financial concerns were not a major factor in their resignations. The study suggests that decreasing nonlicensed employee stress and increasing their personal satisfaction with patient care may decrease employee turnover.

  7. Combined effect of sesamin and soybean phospholipid on hepatic fatty acid metabolism in rats.

    Science.gov (United States)

    Ide, Takashi

    2014-05-01

    We studied the combined effect of sesamin (1:1 mixture of sesamin and episesamine) and soybean phospholipid on lipid metabolism in rats. Male rats were fed diets supplemented with 0 or 2 g/kg sesamin, and containing 0 or 50 g/kg soybean phospholipid, for 19 days. Sesamin and soybean phospholipid decreased serum triacylglycerol concentrations and the combination of these compounds further decreased the parameter in an additive fashion. Soybean phospholipid but not sesamin reduced the hepatic concentration of triacylglycerol. The combination failed to cause a strong decrease in hepatic triacylglycerol concentration, presumably due to the up-regulation of Cd36 by sesamin. Combination of sesamin and soybean phospholipid decreased the activity and mRNA levels of hepatic lipogenic enzymes in an additive fashion. Sesamin strongly increased the parameters of hepatic fatty acid oxidation enzymes. Soybean phospholipid increased hepatic activity of 3-hydroxyacyl-CoA dehydrogenase although it failed to affect the activity of other enzymes involved in fatty acid oxidation. Sesamin strongly increased hepatic concentration of carnitine. Sesamin and soybean phospholipid combination further increased this parameter, accompanying a parallel increase in mRNA expression of carnitine transporter. These changes can account for the strong decrease in serum triacylglycerol in rats fed a diet containing both sesamin and soybean phospholipid.

  8. Continuous Production of Structured Phospholipids in a Packed Red Reactor with Lipase from Thermomyces lanuginosa

    DEFF Research Database (Denmark)

    Vikbjerg, Anders Falk; Peng, Lifeng; Mu, Huiling;

    2005-01-01

    The possibilities of producing structured phospholipids by lipase-catalyzed acidolysis between soybean phospholipids and caprylic acid were examined in continuous packed bed enzyme reactors. Acidolysis reactions were performed in both a solvent system and a solvent-free system with the commercial...

  9. An efficient hydrophilic interaction liquid chromatography separation of 7 phospholipid classes based on a diol column

    NARCIS (Netherlands)

    Zhu, C.; Dane, A.; Spijksma, G.; Wang, M.; Greef, J. van der; Luo, G.; Hankemeier, T.; Vreeken, R.J.

    2012-01-01

    A hydrophilic interaction liquid chromatography (HILIC) - ion trap mass spectrometry method was developed for separation of a wide range of phospholipids. A diol column which is often used with normal phase chromatography was adapted to separate different phospholipid classes in HILIC mode using a m

  10. STRUCTURAL DETERMINATION AND QUANTITATIVE ANALYSIS OF BACTERIAL PHOSPHOLIPIDS USING LIQUID CHROMATOGRAPHY/ELECTROSPRAY IONIZATION/MASS SPECTROMETRY

    Science.gov (United States)

    This report presents a comprehensive spectral analysis of common bacterial phospholipids using electrospray/mass spectrometry (ESI/MS) under both negative and positive ionization conditions. Phospholipids under positive ionization yield sodium-adduct molecular ions which are mos...

  11. Elevation of plasma phospholipid transfer protein increases the risk of atherosclerosis despite lower apolipoprotein B-containing lipoproteins.

    NARCIS (Netherlands)

    J. Lie (Jessica); M.P.G. de Crom (Rini); T. van Gent (Teus); M.J. van Haperen (Rien); L. Scheek (Leo); F. Sadeghi-Niaraki (Farah); A. van Tol (Arie)

    2004-01-01

    textabstractPlasma phospholipid transfer protein (PLTP) transfers phospholipids between lipoproteins and mediates HDL conversion. PLTP-overexpressing mice have increased atherosclerosis. However, mice do not express cholesteryl ester transfer protein (CETP), which is involved in

  12. Substance abuse-specific knowledge transfer or loss? Treatment program turnover versus professional turnover among substance abuse clinicians.

    Science.gov (United States)

    Eby, Lillian T; Laschober, Tanja C; Curtis, Sara L

    2014-01-01

    This longitudinal study investigated the extent to which substance abuse (SA) clinician turnover is associated with SA-specific knowledge loss due to change in professions (professional turnover) versus SA-specific knowledge transfer due to movement from one SA clinical setting to another (treatment program turnover). For this study, clinicians had to have voluntarily left their current treatment program. Eligible clinicians completed a quantitative survey while employed and a qualitative post-employment exit interview 1 year later. Compared to those that exited the SA profession (n = 99), clinicians who changed treatment programs (n = 120) had greater SA-specific formal knowledge and were more likely to be personally in recovery. No differences were found between the two groups in terms of SA-specific practical knowledge.

  13. Recent Advances in Phospholipids from Colostrum, Milk and Dairy By-Products

    Directory of Open Access Journals (Sweden)

    Vito Verardo

    2017-01-01

    Full Text Available Milk is one of the most important foods for mammals, because it is the first form of feed providing energy, nutrients and immunological factors. In the last few years, milk lipids have attracted the attention of researchers due to the presence of several bioactive components in the lipid fraction. The lipid fraction of milk and dairy products contains several components of nutritional significance, such as ω-3 and ω-6 polyunsaturated fatty acids, CLA, short chain fatty acids, gangliosides and phospholipids. Prospective cohort evidence has shown that phospholipids play an important role in the human diet and reinforce the possible relationship between their consumption and prevention of several chronic diseases. Because of these potential benefits of phospholipids in the human diet, this review is focused on the recent advances in phospholipids from colostrum, milk and dairy by-products. Phospholipid composition, its main determination methods and the health activities of these compounds will be addressed.

  14. Recent Advances in Phospholipids from Colostrum, Milk and Dairy By-Products

    Science.gov (United States)

    Verardo, Vito; Gómez-Caravaca, Ana Maria; Arráez-Román, David; Hettinga, Kasper

    2017-01-01

    Milk is one of the most important foods for mammals, because it is the first form of feed providing energy, nutrients and immunological factors. In the last few years, milk lipids have attracted the attention of researchers due to the presence of several bioactive components in the lipid fraction. The lipid fraction of milk and dairy products contains several components of nutritional significance, such as ω-3 and ω-6 polyunsaturated fatty acids, CLA, short chain fatty acids, gangliosides and phospholipids. Prospective cohort evidence has shown that phospholipids play an important role in the human diet and reinforce the possible relationship between their consumption and prevention of several chronic diseases. Because of these potential benefits of phospholipids in the human diet, this review is focused on the recent advances in phospholipids from colostrum, milk and dairy by-products. Phospholipid composition, its main determination methods and the health activities of these compounds will be addressed. PMID:28106745

  15. Theoretical Assessment of Fluorinated Phospholipids in the Design of Liposomal Drug-Delivery Systems

    DEFF Research Database (Denmark)

    Madsen, Jesper J.united st; Fristrup, Peter; Peters, Günther H.J.

    2016-01-01

    Fluorinated phospholipid analogues are investigated as potential substrates for phospholipase A(2) (PLA(2)) using classical molecular dynamics simulations and quantum mechanics/density functional theory calculations. The fluorinated phospholipid analogues are a-fluoro (HF-ProAEL) and alpha......,alpha-difluoro (F-2-ProAEL) conjugates of (R)-1-O-hexadecyl-2-palmitoyl-sn-glycero-3-phoshocholineglycerol (ProAEL). Our results provide a theoretical assessment of the potential usefulness of these fluorinated lipids in the rational design of liposomal drug-delivery systems. The a-fluorine-substituted phospholipid...... at a progressively faster rate; the more electronegative substituent at the a-position effectively lowers the energy barrier for hydrolysis. We conclude that the partially fluorinated phospholipid analogues facilitate rational design of liposomal vesicles of phospholipid mixtures with desirable physicochemical...

  16. Effect of long-term aluminum feeding on lipid/phospholipid profiles of rat brain myelin

    Directory of Open Access Journals (Sweden)

    Dave Kunjan R

    2004-06-01

    Full Text Available Abstract Effect of long-term (90–100 days exposure of rats to soluble salt of aluminum (AlCl3 on myelin lipid profile was examined. The long-term exposure to AlCl3 resulted in a 60 % decrease in the total phospholipid (TPL content while the cholesterol (CHL content increased by 55 %. Consequently the TPL / CHL molar ratio decreased significantly by 62 %. The phospholipid composition of the myelin membrane changed drastically; the proportion of practically all the phospholipid classes decreased by 32 to 60 % except for phosphatidylcholine (PC and phosphatidylethanolamine (PE. Of the latter two, proportion of PC was unchanged while PE increased in proportion by 47 %. Quantitatively, all phospholipid classes decreased by from 42 to 76% with no change in the PE content. However the membrane fluidity was not altered in Al-treated rats. Many of the changes we observe here show striking similarities with the reported phospholipid profiles of Alzheimer brains.

  17. Phospholipid Membrane Protection by Sugar Molecules during Dehydration—Insights into Molecular Mechanisms Using Scattering Techniques

    Science.gov (United States)

    Garvey, Christopher J.; Lenné, Thomas; Koster, Karen L.; Kent, Ben; Bryant, Gary

    2013-01-01

    Scattering techniques have played a key role in our understanding of the structure and function of phospholipid membranes. These techniques have been applied widely to study how different molecules (e.g., cholesterol) can affect phospholipid membrane structure. However, there has been much less attention paid to the effects of molecules that remain in the aqueous phase. One important example is the role played by small solutes, particularly sugars, in protecting phospholipid membranes during drying or slow freezing. In this paper, we present new results and a general methodology, which illustrate how contrast variation small angle neutron scattering (SANS) and synchrotron-based X-ray scattering (small angle (SAXS) and wide angle (WAXS)) can be used to quantitatively understand the interactions between solutes and phospholipids. Specifically, we show the assignment of lipid phases with synchrotron SAXS and explain how SANS reveals the exclusion of sugars from the aqueous region in the particular example of hexagonal II phases formed by phospholipids. PMID:23584028

  18. Phospholipid Membrane Protection by Sugar Molecules during Dehydration-Insights into Molecular Mechanisms Using Scattering Techniques

    Energy Technology Data Exchange (ETDEWEB)

    Garvey, Christopher J.; Lenné, Thomas; Koster, Karen L.; Kent, Ben; Bryant, Gary [ANSTO; (USD); (ANU); (RMIT)

    2014-09-24

    Scattering techniques have played a key role in our understanding of the structure and function of phospholipid membranes. These techniques have been applied widely to study how different molecules (e.g., cholesterol) can affect phospholipid membrane structure. However, there has been much less attention paid to the effects of molecules that remain in the aqueous phase. One important example is the role played by small solutes, particularly sugars, in protecting phospholipid membranes during drying or slow freezing. In this paper, we present new results and a general methodology, which illustrate how contrast variation small angle neutron scattering (SANS) and synchrotron-based X-ray scattering (small angle (SAXS) and wide angle (WAXS)) can be used to quantitatively understand the interactions between solutes and phospholipids. Specifically, we show the assignment of lipid phases with synchrotron SAXS and explain how SANS reveals the exclusion of sugars from the aqueous region in the particular example of hexagonal II phases formed by phospholipids.

  19. Effect of Vesicle-to-Micelle Transition on the Interactions of Phospholipid/Sodium Cholate Mixed Systems with Curcumin in Aqueous Solution.

    Science.gov (United States)

    Zhang, Sha; Wang, Xiaoyong

    2016-08-01

    The role of vesicle-to-micelle transition has been investigated in the interactions of phospholipid vesicles, phospholipid/sodium cholate (NaC) mixed vesicles, and phospholipid/NaC mixed micelles with curcumin in aqueous solution. The addition of NaC causes phospholipid vesicles to transit into phospholipid/NaC mixed vesicles and phospholipid/NaC mixed micelles. Turbidity measurement reveals that the presence of curcumin increases the NaC concentration for the solubilization of phospholipid vesicles, which indicates that the bound curcumin tends to suppress the vesicle-to-micelle transition. The pyrene polarity index and curcumin fluorescence anisotropy measurements suggest that phospholipid/NaC mixed micelles have a more compact structure than that of phospholipid vesicles and phospholipid/NaC mixed vesicles. Curcumin associated with phospholipid vesicles, phospholipid/NaC mixed vesicles, and phospholipid/NaC mixed micelles often results in higher intensities of absorption and fluorescence than those of free curcumin. However, phospholipid/NaC mixed vesicles lead to the highest values of absorption and fluorescence intensities, binding constant, and radical-scavenging capacity with curcumin. The different structures in the phospholipid bilayer of phospholipid/NaC mixed vesicles and the hydrophobic part of phospholipid/NaC mixed micelles where curcumin located are discussed to explain the interaction behaviors of phospholipid/NaC mixed systems with curcumin.

  20. Biochemical Bone Turnover Markers and Osteoporosis in Older Men: Where Are We?

    Directory of Open Access Journals (Sweden)

    Pawel Szulc

    2011-01-01

    Full Text Available In men aged less than 60, the association of serum and urinary levels of biochemical bone turnover markers (BTMs and bone mineral density (BMD is weak or not significant. After this age, higher BTM levels are correlated weakly, but significantly, with lower BMD and faster bone loss. Limited data from the cohort studies suggest that BTM measurement does not improve the prediction of fragility fractures in older men in comparison with age, BMD, history of falls and fragility fractures. Testosterone replacement therapy (TRT decreases bone resorption. During TRT, bone formation markers slightly increase (direct effect on osteoblasts, then decrease (slowdown of bone turnover. Bisphosphonates (alendronate, risedronate, ibandronate, zoledronate induce a rapid decrease in bone resorption followed by a milder decrease in bone formation. In men receiving antiresorptive therapy for prostate cancer, zoledronate, denosumab and toremifene decrease significantly levels of bone resorption and bone formation markers. Teriparatide induced a rapid increase in serum concentrations of bone formation markers followed by an increase in bone resorption. We need more studies on the utility of BTM measurement for the improvement of the persistence and adherence to the anti-osteoporotic treatment in men.