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Sample records for segregated sarcoplasmic reticulum

  1. Biochemical and morphological characterization of light and heavy sarcoplasmic reticulum vesicles

    Energy Technology Data Exchange (ETDEWEB)

    Campbell, K.P.

    1978-01-01

    Light and heavy sarcoplasmic reticulum vesicles isolated from rabbit leg muscle have been used in a study of chloride-induced calcium release. The biochemical and morphological data indicate that light sarcoplasmic reticulum vesicles are derived from the longitudinal reticulum and heavy sarcoplasmic reticulum vesicles are derived from the terminal cisternae of the sarcoplasmic reticulum. The light and heavy sarcoplasmic reticulum vesicles were both able to accumulate calcium in the presence of ATP to amounts greater than 100 nmoles Ca/sup + +/ per mg of protein in less than one minute. Light and heavy sarcoplasmic reticulum vesicles each had a biphasic time course of calcium uptake. The initial uptake was followed by a rapid release after approximately one minute, of 30 to 40% of the accumulated calcium, which was then followed by a slower phase of calcium accumulation. Results indicate that the chloride induced release of calcium may be acting by two mechanisms, osmotic swelling and depolarization. The release of calcium from the light SR vesicles is probably due to osmotic swelling and the release of calcium from the heavy SR vesicles is probably due to depolarization.

  2. Biochemical and morphological characterization of light and heavy sarcoplasmic reticulum vesicles

    Energy Technology Data Exchange (ETDEWEB)

    Campbell, Kevin Peter [Univ. of Rochester, NY (United States)

    1978-01-01

    Light (30 to 32.5% sucrose) and heavy (38.5 to 42% sucrose) sarcoplasmic reticulum vesicles (LSR,HSR) were isolated from rabbit leg muscle using a combination of differential centrifugation and isopycnic zonal ultracentrifugation. Thin-section electron microscopy of LSR vesicles reveals empty vesicles of various sizes and shapes whereas the HSR vesicles appear as rounded vesicles of uniform size filled with electron dense material, similar to that seen in the terminal cisternae of the sarcoplasmic reticulum. The sucrose HSR vesicles have an additional morphological feature which appears as membrane projections that resemble the SR feet. The freeze-fracture morphology of either type of SR reveals an asymmetric distribution of intramembraneous particles in the same orientation and distribution as the sarcoplasmic reticulum in vivo. Biochemical studies were made on the content of Ca, Mg, ATPase, and protein of the vesicles and phosphorylation of the vesicles. The biochemical and morphological data indicate that the LSR is derived from the longitudinal sarcoplasmic reticulum and the HSR is derived from the terminal cisternae of the sarcoplasmic reticulum, contains junctional SR membrane and has three unique proteins (calsequestrin, an intrinsic 30,000 dalton protein and a 9000 dalton proteolipid).

  3. Porcine malignant hyperthermia susceptibility: hypersensitive calcium-release mechanism of skeletal muscle sarcoplasmic reticulum.

    Science.gov (United States)

    O'Brien, P J

    1986-01-01

    This study tested the hypothesis that calcium-release from sarcoplasmic reticulum isolated from malignant hyperthermia swine had abnormal concentration-dependency on release modulators. Halothane stimulated half-maximal calcium-release at similar concentrations for malignant hyperthermia and control sarcoplasmic reticulum (0.10 +/- 0.04 mM). However, concentrations causing half-maximal calcium-release were lower for malignant hyperthermia sarcoplasmic reticulum (P less than 0.001) by an order of magnitude for Ca2+ (28.1 +/- 8.3 versus 1.23 +/- 0.45 nM), adenosine triphosphate (0.33 +/- 0.09 versus 0.023 +/- 0.014 mM) and caffeine (7.79 +/- 1.56 versus 0.80 +/- 0.44 mM). Half-maximal inhibition by Mg2+ occurred at threefold higher concentrations for malignant hyperthermia sarcoplasmic reticulum (0.23 +/- 0.02 versus 0.78 +/- 0.17 mM). The Ca2+-sensitivity curves for calcium-release by sarcoplasmic reticulum isolated from heterozygotes for the malignant hyperthermia-defect were indistinguishable from the averages of the curves for controls and malignant hyperthermia-homozygotes. Results of this study suggest that malignant hyperthermia is initiated due to a hypersensitive calcium-release mechanism which is inherited in an autosomal, codominant pattern and may be diagnosed using calcium-release sensitivity-tests on isolated sarcoplasmic reticulum. Images Fig. 1. PMID:3742367

  4. Cardiac sarcoplasmic reticulum

    International Nuclear Information System (INIS)

    Jacobson, M.S.; Ambudkar, I.S.; Young, E.P.; Naseem, S.M.; Heald, F.P.; Shamoo, A.E.

    1985-01-01

    The effect on the cardiac sarcoplasmic reticulum of an atherogenic (1% cholesterol) diet fed during the neonatal vs the juvenile period of life was studied in Yorkshire swine. Male piglets were randomly assigned at birth to 1 of 4 groups: group I (control), group II (lactation feeding), group III (juvenile period feeding) and group IV (lactation and juvenile feeding). All animals were killed at 55 weeks of age and cardiac sarcoplasmic reticulum (SR) isolated for assay of calcium uptake, Ca 2+ -Mg 2+ ATPase activity, and lipid analysis by thin-layer chromatography and gas chromatography. The amount of cholesterol/mg SR protein and the cholesterol/phospholipid ratio were higher in the animals fed during lactation (groups II and IV) and lower in those fed only during the juvenile period (group III). Phospholipid fatty acid patterns as measured by gas chromatography were unaltered in any group. Calcium uptake was markedly diminished in all experimental conditions: group II 47%, group III 65% and group IV 96%. Compared to the observed changes in calcium transport, the ATP hydrolytic activity was relatively less affected. Only in group IV a significant decrease (41%) was seen. Groups II and III show no change in ATP hydrolytic activity. The decrease in calcium uptake and altered cholesterol/phospholipid ratio without effect on ATP hydrolytic activity is consistent with an uncoupling of calcium transport related to the atherogenic diet in early life. (author)

  5. Sarcoplasmic reticulum function in slow- and fast-twitch skeletal muscles from mdx mice.

    Science.gov (United States)

    Divet, Alexandra; Huchet-Cadiou, Corinne

    2002-08-01

    The aim of the present study was to establish whether alterations in sarcoplasmic reticulum function are involved in the abnormal Ca(2+) homeostasis of skeletal muscle in mice with muscular dystrophy ( mdx). The properties of the sarcoplasmic reticulum and contractile proteins of fast- and slow-twitch muscles were therefore investigated in chemically skinned fibres isolated from the extensor digitorum longus (EDL) and soleus muscles of normal (C57BL/10) and mdx mice at 4 and 11 weeks of development. Sarcoplasmic reticulum Ca(2+) uptake, estimated by the Ca(2+) release following exposure to caffeine, was significantly slower in mdx mice, while the maximal Ca(2+) quantity did not differ in either type of skeletal muscle at either stage of development. In 4-week-old mice spontaneous sarcoplasmic reticulum Ca(2+) leakage was observed in EDL and soleus fibres and this was more pronounced in mdx mice. In addition, the maximal Ca(2+)-activated tension was smaller in mdx than in normal fibres, while the Ca(2+) sensitivity of the contractile apparatus was not significantly different. These results indicate that mdx hindlimb muscles are affected differently by the disease process and suggest that a reduced ability of the Ca(2+)-ATPase to load Ca(2+) and a leaky sarcoplasmic reticulum membrane may be involved in the altered intracellular Ca(2+) homeostasis.

  6. Calcium uptake by sarcoplasmic reticulum in the presence of organophosphorus insecticide methyl-parathion

    International Nuclear Information System (INIS)

    Blasiak, J.

    1995-01-01

    Using an isotope labelling technique it has been shown that an organophosphorus insecticide methyl parathion (0,0-diethyl 0-4-nitrophenyl phosphorothionate) depressed calcium uptake by sarcoplasmic reticulum isolated from rabbit hind leg muscle. The effect was significant for insecticide concentrations of 50 and 100 μM and was dose-dependent. The insecticide exerted a more pronounced effect on calcium uptake in the presence of ATP in the reticulum environment than in the absence of ATP. The inhibitory action of methyl parathion on Ca 2+ accumulation by sarcoplasmic reticulum can cause a rise in myoplasmic free Ca 2+ , the essential prerequisite for contracture activation. Because methyl parathion, as well as other organophosphorus insecticides, is primarily neurotoxic, evidence of non-specific effect could be important for assessing its environmental safety. (author). 20 refs, 2 figs

  7. Purification of a sarcoplasmic reticulum protein that binds Ca2+ and plasma lipoproteins

    International Nuclear Information System (INIS)

    Hofmann, S.L.; Brown, M.S.; Lee, E.; Pathak, R.K.; Anderson, R.G.; Goldstein, J.L.

    1989-01-01

    A protein in the sarcoplasmic reticulum of rabbit skeletal and cardiac muscle was identified because of its ability to bind 125I-labeled low density lipoprotein (LDL) with high affinity after sodium dodecyl sulfate-polyacrylamide gel electrophoresis. This protein, referred to as the 165-kDa protein, is restricted to striated muscle. It was not detected in 14 other tissues, including several that contain smooth muscle, but it appears in rat L6 myoblasts when they differentiate into myocytes. Immunofluorescence and immunoelectron microscopic studies revealed that the protein is present throughout the sarcoplasmic reticulum and the terminal cisternae. It binds 45Ca2+ on nitrocellulose blots and stains metachromatically with Stains-all, a cationic dye that stains Ca2+-binding proteins. It does not appear to be a glycoprotein, and it appears slightly larger than the 160-kDa glycoprotein previously described in sarcoplasmic reticulum. The 165-kDa protein binds LDL, beta-migrating very low density lipoprotein, and a cholesterol-induced high density lipoprotein particle that contains apoprotein E as its sole apoprotein with much higher affinity than it binds high density lipoprotein. The protein is stable to boiling and to treatment with sodium dodecyl sulfate, but it becomes sensitive to these treatments when its cystine residues are reduced and alkylated. The protein was purified 1300-fold to apparent homogeneity from rabbit skeletal muscle membranes. It differs from the cell surface LDL receptor in that (1) its apparent molecular weight is not changed by reduction and alkylation; (2) it is present in Watanabe-heritable hyperlipidemic rabbits, which lack functional LDL receptors; (3) binding of lipoproteins is not inhibited by EDTA; and (4) it is located within the lumen of the sarcoplasmic reticulum where it has no access to plasma lipoproteins

  8. Structural role of lipids in mitochondrial and sarcoplasmic reticulum membranes: freeze-fracture electron microscopy studies

    Energy Technology Data Exchange (ETDEWEB)

    Packer, L; Mehard, C W; Meissner, G; Zahler, W L; Fleischer, S

    1974-01-01

    The role of phospholipid in the structure of the membranes of beef heart mitochondria and of the sarcoplasmic reticulum membranes from rabbit skeletal muscle has been investigated by freeze-fracture electron microscopy. Progressive removal of membrane phospholipids, by phospholipase A treatment or detergent treatment, or by organic solvent extraction, results in loss of the smooth background seen in membrane fracture faces and decreased ability of membrane to undergo freeze fracture to yield fracture faces. Instead cross-sections of vesicles or particle clusters are observed. Sarcoplasmic reticulum vesicles have a 9 to 1 asymmetry in the distribution of particles between the convex and concave fracture faces. There is also a wide range of particle size distribution in both of these fracture faces with 85-A particles in greatest number. The removal of membrane associated proteins by detergent extraction does not appreciably change the distribution in particle size. Sarcoplasmic reticulum vesicles were dissolved with detergent and reassembled to form membrane vesicles containing mainly one protein (approx. 90%), i.e., the Ca/sup 2 +/ pump protein, and with a ratio of lipid to protein similar to the original membrane. The reconstituted vesicles readily underwent freeze fracture but the asymmetric particle distribution between the fracture faces was no longer observed. The size distribution of particles in the reconstituted membrane, consisting mainly of Ca/sup 2 +/ pump protein, and phospholipid, was similar in heterogeneity to the original sarcoplasmic reticulum membrane. Thus the heterogeneity in particle size could reflect variation in the orientation of the Ca/sup 2 +/ pump protein within the membrane.

  9. Effect of ionizing radiation on catalytic properties of Ca2+-ATP-ase from sarcoplasmic reticulum of skeletal muscle

    International Nuclear Information System (INIS)

    Bagel', I.M.; Shafranovskaya, E.V.; Gorokh, G.A.; Markova, A.G.

    1999-01-01

    It was studied kinetic and thermodynamic characteristics of Ca 2+ -ATP-ase of rat skeletal muscle (membranes of sarcoplasmic reticulum) after irradiation in doses 0,5, 4,0 and 8,0 Gy. It was shown that external gamma-irradiation at different doses changed kinetic and thermodynamic characteristics of the enzyme of sarcoplasmic reticulum membranes of skeletal muscle. These alterations probably correlate with disbalance of hormonal regulation of intracellular calcium metabolism and changes in membrane structure and functions

  10. Investigation of function similarities between the sarcoplasmic reticulum and platelet calcium-dependent adenosinetriphosphatases with the inhibitors quercetin and calmidazolium

    International Nuclear Information System (INIS)

    Fischer, T.H.; Campbell, K.P.; White, G.C. II

    1987-01-01

    The platelet and skeletal sarcoplasmic reticulum calcium-dependent adenosinetriphosphatases (Ca 2+ -ATPases) were functionally compared with respect to substrate activation by steady-state kinetic methods using the inhibitors quercetin and calmidazolium. Quercetin inhibited platelet and sarcoplasmic reticulum Ca 2+ -ATPase activities in a dose-dependent manner with IC 50 values of 25 and 10 μM, respectively. Calmidazolium also inhibited platelet and sarcoplasmic reticulum Ca 2+ -ATPase activities, with half-maximal inhibition measured at 5 and 4 μM, respectively. Both inhibitors also affected the [ 45 Ca] calcium transport activity of intact platelet microsomes at concentrations similar to those which reduced Ca 2+ -ATPase activity. These inhibitors were then used to examine substrate ligation by the platelet and sarcoplasmic reticulum calcium pump proteins. For both Ca 2+ -ATPase proteins, quercetin has an affinity for the E-Ca 2 (fully ligated with respect to calcium at the exterior high-affinity calcium binding sites, unligated with respect to ATP) conformational state of the protein that is approximately 10-fold grater than for other conformational states in the hydrolytic cycle. Quercetin can thus be considered a competitive inhibitor of the calcium pump proteins with respect to ATP. In contrast to the effect of quercetin, calmidazolium interacts with the platelet and sarcoplasmic reticulum Ca 2+ -ATPases in an uncompetitive manner. The dissociation constants for this inhibitor for the different conformational states of the calcium pump proteins were similar, indicating that calmidazolium has equal affinity for all of the reaction intermediates probed. These observations indicate that the substrate ligation processes are similar for the two pump proteins. This supports the concept that the hydrolytic cycles of the two proteins are comparable

  11. Molecular cloning and expression of cDNA encoding a lumenal calcium binding glycoprotein from sarcoplasmic reticulum

    International Nuclear Information System (INIS)

    Leberer, E.; Charuk, J.H.M.; MacLennan, D.H.; Green, N.M.

    1989-01-01

    Antibody screening was used to isolate a cDNA encoding the 160-kDa glycoprotein of rabbit skeletal muscle sarcoplasmic reticulum. The cDNA is identical to that encoding the 53-kDa glycoprotein except that it contains an in-frame insertion of 1,308 nucleotides near its 5' end, apparently resulting from alternative splicing. The protein encoded by the cDNA would contain a 19-residue NH 2 -terminal signal sequence and a 453-residue COOH-terminal sequence identical to the 53-kDa glycoprotein. It would also contain a 436-amino acid insert between these sequences. This insert would be highly acidic, suggesting that it might bind Ca 2+ . The purified 160-kDa glycoprotein and the glycoprotein expressed in COS-1 cells transfected with cDNA encoding the 160-kDa glycoprotein were shown to bind 45 C 2+ in a gel overlay assay. The protein was shown to be located in the lumen of the sarcoplasmic reticulum and to be associated through Ca 2+ with the membrane. The authors propose that this lumenal Ca 2+ binding glycoprotein of the sarcoplasmic reticulum be designated sarcalumenin

  12. Effects of inorganic phosphate and ADP on calcium handling by the sarcoplasmic reticulum in rat skinned cardiac muscles.

    Science.gov (United States)

    Xiang, J Z; Kentish, J C

    1995-03-01

    The aim was to investigate whether, and how, increases in inorganic phosphate (Pi) and ADP, similar to those occurring intracellularly during early myocardial ischaemia, affect the calcium handling of the sarcoplasmic reticulum. Rat ventricular trabeculae were permeabilised with saponin. The physiological process of calcium induced calcium release (CICR) from the muscle sarcoplasmic reticulum was triggered via flash photolysis of the "caged Ca2+", nitr-5. Alternatively, calcium release was induced by rapid application of caffeine to give an estimate of sarcoplasmic reticular calcium loading. The initial rate of sarcoplasmic reticular calcium pumping was also assessed by photolysis of caged ATP at saturating [Ca2+]. Myoplasmic [Ca2+] (using fluo-3) and isometric force were measured. Pi (2-20 mM) significantly depressed the magnitude of CICR and the associated force transient. Sarcoplasmic reticular calcium loading was inhibited even more than CICR by Pi, suggesting that reduced calcium loading could account for all of the inhibitory effect of Pi on CICR and that Pi may slightly activate the calcium release mechanism. The reduced sarcoplasmic reticular calcium loading seemed to be due to a fall in the free energy of ATP hydrolysis (delta GATP) available for the calcium pump, since equal decreases in delta GATP produced by adding both Pi and ADP in various ratios caused similar falls in the calcium loading of the sarcoplasmic reticulum. The caged ATP experiments indicated that Pi (20 mM) did not affect the rate constant of sarcoplasmic reticular calcium uptake. ADP (10 mM) alone, or with 1 mM Pi, inhibited calcium loading. In spite of this, ADP (10 mM) did not alter CICR and, when 1 mM Pi was added, ADP increased CICR above control. An increase in intracellular Pi reduces sarcoplasmic reticular calcium loading and thus depresses the CICR. This could be an important contributing factor in the hypoxic or ischaemic contractile failure of the myocardium. However the

  13. Dynamic Changes in Sarcoplasmic Reticulum Structure in Ventricular Myocytes

    Directory of Open Access Journals (Sweden)

    Amanda L. Vega

    2011-01-01

    sarcoplasmic reticulum (SR and the sarcolemma where Ca2+ release is activated. Here, we tested the hypothesis that the SR is a structurally inert organelle in ventricular myocytes. Our data suggest that rather than being static, the SR undergoes frequent dynamic structural changes. SR boutons expressing functional ryanodine receptors moved throughout the cell, approaching or moving away from the sarcolemma of ventricular myocytes. These changes in SR structure occurred in the absence of changes in [Ca2+] during EC coupling. Microtubules and the molecular motors dynein and kinesin 1(Kif5b were important regulators of SR motility. These findings support a model in which the SR is a motile organelle capable of molecular motor protein-driven structural changes.

  14. Disturbances of the sarcoplasmic reticulum and transverse tubular system in 24-h electrostimulated fast-twitch skeletal muscle

    DEFF Research Database (Denmark)

    Frías, J A; Cadefau, J A; Prats, C

    2005-01-01

    Chronic low-frequency stimulation of rabbit tibialis anterior muscle over a 24-h period induces a conspicuous loss of isometric tension that is unrelated to muscle energy metabolism (J.A. Cadefau, J. Parra, R. Cusso, G. Heine, D. Pette, Responses of fatigable and fatigue-resistant fibres of rabbit...... muscle to low-frequency stimulation, Pflugers Arch. 424 (1993) 529-537). To assess the involvement of sarcoplasmic reticulum and transverse tubular system in this force impairment, we isolated microsomal fractions from stimulated and control (contralateral, unstimulated) muscles on discontinuous sucrose...... of muscles stimulated for 24 h underwent acute changes in the pattern of protein bands. First, light fractions from longitudinal sarcoplasmic reticulum, enriched in Ca2+-ATPase activity, R1 and R2, were greatly reduced (67% and 51%, respectively); this reduction was reflected in protein yield of crude...

  15. Methods for Creating and Animating a Computer Model Depicting the Structure and Function of the Sarcoplasmic Reticulum Calcium ATPase Enzyme.

    Science.gov (United States)

    Chen, Alice Y.; McKee, Nancy

    1999-01-01

    Describes the developmental process used to visualize the calcium ATPase enzyme of the sarcoplasmic reticulum which involves evaluating scientific information, consulting scientists, model making, storyboarding, and creating and editing in a computer medium. (Author/CCM)

  16. [ACTIVITY OF Ca2+,Mg(2+)-ATPase OF SARCOPLASMIC RETICULUM AND CONTRACTION STRENGTH OF THE FROG SKELETAL MUSCLES UNDER THE EFFECT OF ORGANOPHOSPHORUS INSECTICIDES].

    Science.gov (United States)

    Nozdrenko, D M; Korchinska, L V; Soroca, V M

    2015-01-01

    The results of an experimental study of organophosphorus insecticides, including pirimiphosmethyl, diazinon and chlorpyrifos caused a decline of the contraction properties in m. tibialis anterior fiber bundles of Rana temporaria, as well as sarcoplasmic reticulum Ca2+, Mg(2+)-ATPase enzymatic activity reduction are outlined in this paper. Concentration-dependent strengths response diminishing in isolated skeletal muscle fiber bundles as a result of non-cholinergic influence of organophosphorus insecticides were found. A decrease of Ca2+, Mg(2+)-ATPase enzymatic activity in sarcoplasmic reticulum was observed after administration of each insecticide. The most significant inhibition of this enzyme was observed when using chlorpyrifos.

  17. Effects of exercise training and exhaustion on 45Ca uptake by rat skeletal muscle mitochondria and sarcoplasmic reticulum

    International Nuclear Information System (INIS)

    Bonner, H.W.; Leslie, S.W.; Combs, A.B.; Tate, C.A.

    1976-01-01

    Mitochondrial and sarcoplasmic reticular 45 Ca 2+ uptake and Ca 2+ -ATPase activity were determined in skeletal muscle from exercise trained and non-trained rats at rest or following short-term exhaustive exercise. In trained rats exercised to exhaustion, mitochondrial 45 Ca 2+ uptake was significantly depressed when compared to non-trained rats at rest. Ca 2+ -ATPase activity of sarcoplasmic reticulum from trained rats exercised to exhaustion was significantly increased as compared to trained rats at rest. These data suggest that the disruptive influence of Ca 2+ accumulation in mitochondria isolated following exhaustive exercise may be diminished as a result of training

  18. Detection, Properties, and Frequency of Local Calcium Release from the Sarcoplasmic Reticulum in Teleost Cardiomyocytes

    OpenAIRE

    Llach, Anna; Molina, Cristina E.; Alvarez Lacalle, Enrique; Tort, Lluis; Benítez, Raul; Hove, Leif

    2011-01-01

    Calcium release from the sarcoplasmic reticulum (SR) plays a central role in the regulation of cardiac contraction and rhythm in mammals and humans but its role is controversial in teleosts. Since the zebrafish is an emerging model for studies of cardiovascular function and regeneration we here sought to determine if basic features of SR calcium release are phylogenetically conserved. Confocal calcium imaging was used to detect spontaneous calcium release (calcium sparks and waves) from...

  19. Activity of Ca(2+,Mg(2+-ATPase of sarcoplasmic reticulum and contraction strength of the frog skeletal muscles under the effect of organophosphorus insecticides

    Directory of Open Access Journals (Sweden)

    D. M. Nozdrenko

    2015-08-01

    Full Text Available The results of an experimental study of organo­phosphorus insecticides, including pirimiphosmethyl, diazinon and chlorpyrifos caused a decline of the contraction properties in m. tibialis anterior fiber bundles of Rana temporaria, as well as sarcoplasmic reticulum Ca2+,Mg2+-ATPase enzymatic activity reduction are outlined in this paper. Concentration-dependent strengths response diminishing in isolated skeletal muscle fiber bundles as a result of non-cholinergic influence of organophosphorus insecticides were found. A decrease of Ca2+,Mg2+-ATPase enzymatic activity in sarcoplasmic reticulum was observed after administration of each insecticide. The most significant inhibition of this enzyme was observed when using chlorpyrifos.

  20. Cardiac sarcoplasmic reticulum. Effects of an atherogenic diet during the neonatal and juvenile period

    Energy Technology Data Exchange (ETDEWEB)

    Jacobson, M S; Ambudkar, I S; Young, E P; Naseem, S M; Heald, F P; Shamoo, A E [Maryland Univ., College Park (USA). School of Medicine

    1985-04-01

    The effect on the cardiac sarcoplasmic reticulum of an atherogenic (1% cholesterol) diet fed during the neonatal vs the juvenile period of life was studied in Yorkshire swine. Male piglets were randomly assigned at birth to 1 of 4 groups: group I (control), group II (lactation feeding), group III (juvenile period feeding) and group IV (lactation and juvenile feeding). All animals were killed at 55 weeks of age and cardiac sarcoplasmic reticulum (SR) isolated for assay of calcium uptake, Ca/sup 2 +/-Mg/sup 2 +/ ATPase activity, and lipid analysis by thin-layer chromatography and gas chromatography. The amount of cholesterol/mg SR protein and the cholesterol/phospholipid ratio were higher in the animals fed during lactation (groups II and IV) and lower in those fed only during the juvenile period (group III). Phospholipid fatty acid patterns as measured by gas chromatography were unaltered in any group. Calcium uptake was markedly diminished in all experimental conditions: group II 47%, group III 65% and group IV 96%. Compared to the observed changes in calcium transport, the ATP hydrolytic activity was relatively less affected. Only in group IV a significant decrease (41%) was seen. Groups II and III show no change in ATP hydrolytic activity. The decrease in calcium uptake and altered cholesterol/phospholipid ratio without effect on ATP hydrolytic activity is consistent with an uncoupling of calcium transport related to the atherogenic diet in early life.

  1. Different thermostabilities of sarcoplasmic reticulum (Ca2+ + Mg2+)-ATPases from rabbit and trout muscles.

    Science.gov (United States)

    de Toledo, F G; Albuquerque, M C; Goulart, B H; Chini, E N

    1995-05-01

    Trout and rabbit (Ca2+ + Mg2+)-ATPases from sarcoplasmic reticulum were compared for differences in thermal inactivation and susceptibility to trypsin digestion. The trout ATPase is more heat-sensitive than the rabbit ATPase and is stabilized by Ca2+, Na+, K+ and nucleotides. Solubilization of both ATPases shows that the two ATPases have different protein-intrinsic inactivation kinetics. When digested by trypsin, the two ATPases display different cleavage patterns. The present results indicate that the trout and rabbit ATPases have dissimilarities in protein structure that may explain the differences in thermal inactivation kinetics.

  2. Biochemical and morphological characterization of light and heavy sarcoplasmic reticulum vesicles. Volume I

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    Campbell, Kevin Peter [Univ. of Rochester, NY (United States)

    1978-01-01

    Light (30 to 32.5% sucrose) and heavy (38.5 to 42% sucrose) sarcoplasmic reticulum vesicles (LSR, HSR) were isolated from rabbit leg muscle. They were then diluted and washed with sucrose or KCl and referred to as sucrose or KCl washed vesicles. Thin-section electron microscopy of LSR vesicles reveals empty vesicles of various sizes and shapes where as the HSR vesicles appear as rounded vesicles of uniform size filled with electron dense material. The LSR consists of predominantly Ca2+ + Mg2+ ATPase (80 to 90%), a small amount of the high affinity Ca binding protein (5%), and a 5000 dalton proteolipid. The sucrose HSR vesicles contain the Ca2+ + Mg2+ ATPase (50%), Calsequestrin (25%), high affinity Ca binding protein (5%), one extrinsic 34,000 dalton protein (3%), one intrinsic 30,000 dalton protein (3%), a 9000 dalton proteolipid, and a 5000 dalton proteolipid. The sucrose--washed HSR vesicles contain greater than three times the calcium content of the sucrose washed LSR vesicles where as the KCl--washed vesicles contain less than 15 nmoles Ca2+ mg of protein each. The light and heavy sarcoplasmic reticulum vesicles were both able to accumulate calcium in the presence of ATP. Exchange of methanesulfonate for chloride resulted in the release of calcium from both the light and heavy SR vesicles. Sucrose causes a slight inhibition of chloride--induced calcium release from the heavy SR vesicles but it greatly reduces the release of calcium from the light SR vesicles. Sodium dantrolene (20 uM) has no effect on the release of calcium from the light SR vesicles but it inhibits the release of calcium from the heavy SR vesicles. The results indicate that the chloride--induced release of calcium may be acting by two mechanisms, osmotic swelling and depolarization.

  3. Biochemical and morphological characterization of light and heavy sarcoplasmic reticulum vesicles. Volume I

    International Nuclear Information System (INIS)

    Campbell, K.P.

    1978-01-01

    Light (30 to 32.5% sucrose) and heavy (38.5 to 42% sucrose) sarcoplasmic reticulum vesicles (LSR, HSR) were isolated from rabbit leg muscle. They were then diluted and washed with sucrose or KCl and referred to as sucrose or KCl washed vesicles. Thin-section electron microscopy of LSR vesicles reveals empty vesicles of various sizes and shapes where as the HSR vesicles appear as rounded vesicles of uniform size filled with electron dense material. The LSR consists of predominantly Ca 2+ + Mg 2+ ATPase (80 to 90%), a small amount of the high affinity Ca binding protein (5%), and a 5000 dalton proteolipid. The sucrose HSR vesicles contain the Ca 2+ + Mg 2+ ATPase (50%), Calsequestrin (25%), high affinity Ca binding protein (5%), one extrinsic 34,000 dalton protein (3%), one intrinsic 30,000 dalton protein (3%), a 9000 dalton proteolipid, and a 5000 dalton proteolipid. The sucrose--washed HSR vesicles contain greater than three times the calcium content of the sucrose washed LSR vesicles where as the KCl--washed vesicles contain less than 15 nmoles Ca 2+ /mg of protein each. The light and heavy sarcoplasmic reticulum vesicles were both able to accumulate calcium in the presence of ATP. Exchange of methanesulfonate for chloride resulted in the release of calcium from both the light and heavy SR vesicles. Sucrose causes a slight inhibition of chloride--induced calcium release from the heavy SR vesicles but it greatly reduces the release of calcium from the light SR vesicles. Sodium dantrolene (20 uM) has no effect on the release of calcium from the light SR vesicles but it inhibits the release of calcium from the heavy SR vesicles. The results indicate that the chloride--induced release of calcium may be acting by two mechanisms, osmotic swelling and depolarization

  4. Specific protein-protein interactions of calsequestrin with junctional sarcoplasmic reticulum of skeletal muscle

    International Nuclear Information System (INIS)

    Damiani, E.; Margreth, A.

    1990-01-01

    Minor protein components of triads and of sarcoplasmic reticulum (SR) terminal cisternae (TC), i.e. 47 and 37 kDa peptides and 31-30 kDa and 26-25 kDa peptide doublets, were identified from their ability to bind 125 I calsequestrin (CS) in the presence of EGTA. The CS-binding peptides are specifically associated with the junctional membrane of TC, since they could not be detected in junctional transverse tubules and in longitudinal SR fragments. The 31-30 kDa peptide doublet, exclusively, did not bind CS in the presence of Ca 2+ . Thus, different types of protein-protein interactions appear to be involved in selective binding of CS to junctional TC

  5. The influence of ionizing radiation on the structure of Ca-ATPase hydrophobic fragment of skeletal muscle sarcoplasmic reticulum

    International Nuclear Information System (INIS)

    Vojtsitskij, V.M.; Fedorov, A.N.; Lugovskoj, Eh.B.; Derzskaya, S.G.; Khizhnyak, S.V.; Kurskij, M.D.; Kucherenko, N.E.

    1990-01-01

    Early (1 and 24 h) after X-irradiation with a dose of 0.21 C/kg changes occurred in the acceptibility of the polypeptide chain parts of sarcoplasmic reticulum Ca-ATPase for the effect of trypsin. The analysis of the results of studying the structural and functional properties of a hydrophobic fragment of this enzyme in the control and after irradiation permitted to define the part of the Ca-ATPase polypeptide chain that provided ion selectivity of the fragment

  6. Vanilloid receptor expressed in the sarcoplasmic reticulum of rat skeletal muscle

    International Nuclear Information System (INIS)

    Xin Hong; Tanaka, Hideyuki; Yamaguchi, Maki; Takemori, Shigeru; Nakamura, Akio; Kohama, Kazuhiro

    2005-01-01

    Vanilloid receptor subtype 1 (VR1) was cloned as a capsaicin receptor from neuronal cells of dorsal root ganglia. VR1 was subsequently found in a few non-neuronal tissues, including skeletal muscle [Onozawa et al., Tissue distribution of capsaicin receptor in the various organs of rats, Proc. Jpn. Acad. Ser. B 76 (2000) 68-72]. We confirmed the expression of VR1 in muscle cells using the RT-PCR method and Western blot analysis. Immunostaining studies with a confocal microscope and an electron microscope indicated that VR1 was present in the sarcoplasmic reticulum (SR), a store of Ca 2+ . The SR releases Ca 2+ to cause a contraction when a muscle is excited. However, SR still releases a small amount of Ca 2+ under relaxed conditions. We found that this leakage was enhanced by capsaicin and was antagonized by capsazepine, a capsaicin blocker, indicating that leakage of Ca 2+ occurs through a channel composed of VR1

  7. Specific binding of [3H]LY186126, an analogue of indolidan (LY195115), to cardiac membranes enriched in sarcoplasmic reticulum vesicles

    International Nuclear Information System (INIS)

    Kauffman, R.F.; Utterback, B.G.; Robertson, D.W.

    1989-01-01

    LY186126 was found to be a potent inhibitor of type IV cyclic AMP phosphodiesterase located in the sarcoplasmic reticulum of canine cardiac muscle. This compound, a close structural analogue of indolidan (LY195115), was prepared in high specific activity, tritiated form to study the positive inotropic receptor(s) for cardiotonic phosphodiesterase inhibitors such as indolidan and milrinone. A high-affinity binding site for [ 3 H]LY186126 was observed (Kd = 4 nM) in purified preparations of canine cardiac sarcoplasmic reticulum vesicles. Binding was proportional to vesicle protein, was inactivated by subjecting membranes to proteolysis or boiling, and was dependent on added Mg2+. Scatchard analysis suggested the presence of a single class of binding sites in the membrane preparation. Indolidan, milrinone, and LY186126 (all at 1 microM) produced essentially complete displacement of bound [ 3 H]LY186126, while nifedipine, propranolol, and prazosin had little or no effect at this concentration. This represents the first reported use of a radioactive analogue to label the inotropic receptor for cardiotonic phosphodiesterase inhibitors. The results suggest that [ 3 H]LY186126 is a useful radioligand for examining the subcellular site(s) responsible for positive inotropic effects of these drugs

  8. Characterization of sarcoplasmic reticulum Ca(2+) ATPase pumps in muscle of patients with myotonic dystrophy and with hypothyroid myopathy.

    Science.gov (United States)

    Guglielmi, V; Oosterhof, A; Voermans, N C; Cardani, R; Molenaar, J P; van Kuppevelt, T H; Meola, G; van Engelen, B G; Tomelleri, G; Vattemi, G

    2016-06-01

    Sarcoplasmic/endoplasmic reticulum Ca(2+) ATPase (SERCA) pumps play the major role in lowering cytoplasmic calcium concentration in skeletal muscle by catalyzing the ATP-dependent transport of Ca(2+) from the cytosol to the lumen of the sarcoplasmic reticulum (SR). Although SERCA abnormalities have been hypothesized to contribute to the dysregulation of intracellular Ca(2+) homeostasis and signaling in muscle of patients with myotonic dystrophy (DM) and hypothyroid myopathy, the characterization of SERCA pumps remains elusive and their impairment is still unclear. We assessed the activity of SR Ca(2+)-ATPase, expression levels and fiber distribution of SERCA1 and SERCA2, and oligomerization of SERCA1 protein in muscle of patients with DM type 1 and 2, and with hypothyroid myopathy. Our data provide evidence that SR Ca(2+) ATPase activity, protein levels and muscle fiber distribution of total SERCA1 and SERCA2, and SERCA1 oligomerization pattern are similar in patients with both DM1 and DM2, hypothyroid myopathy and in control subjects. We prove that SERCA1b, the neonatal isoform of SERCA1, is expressed at protein level in muscle of patients with DM2 and, in lower amount, of patients with DM1. Our present study demonstrates that SERCA function is not altered in muscle of patients with DM and with hypothyroid myopathy. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Preparation of a highly concentrated, completely monomeric, active sarcoplasmic reticulum Ca2+-ATPase.

    Science.gov (United States)

    Lüdi, H; Hasselbach, W

    1985-11-21

    Sarcoplasmic reticulum vesicles from fast skeletal muscle were partially delipidated with sodium cholate at high ionic strength and sedimented in a discontinuous sucrose gradient. Phospholipid content was reduced from 0.777 mumol/mg protein to 0.242 mumol/mg protein. As judged from gel electrophoresis and high pressure liquid gel chromatography, accessory proteins were removed during centrifugation and the Ca2+-ATPase was obtained in an almost pure form. Addition of myristoylglycerophosphocholine (1 mg/mg protein) reactivates ATPase and dinitrophenylphosphatase activity to the same degree obtained with native vesicles. Using the analytical ultracentrifuge it could be demonstrated that the reactivated Ca2+-ATPase was present exclusively in a monomeric state. These results were obtained at high and low ionic strength and up to a protein concentration of 10 mg/ml. Therefore this preparation should be very useful to investigate differences between oligomeric and monomeric Ca2+-ATPase.

  10. Modulation of sarcoplasmic reticulum calcium release by calsequestrin in cardiac myocytes

    Directory of Open Access Journals (Sweden)

    SANDOR GYÖRKE

    2004-01-01

    Full Text Available Calsequestrin (CASQ2 is a high capacity Ca-binding protein expressed inside the sarcoplasmic reticulum (SR. Mutations in the cardiac calsequestrin gene (CASQ2 have been linked to arrhythmias and sudden death induced by exercise and emotional stress. We have studied the function of CASQ2 and the consequences of arrhythmogenic CASQ2 mutations on intracellular Ca signalling using a combination of approaches of reverse genetics and cellular physiology in adult cardiac myocytes. We have found that CASQ2 is an essential determinant of the ability of the SR to store and release Ca2+ in cardiac muscle. CASQ2 serves as a reservoir for Ca2+ that is readily accessible for Ca2+-induced Ca2+ release (CICR and also as an active Ca2+ buffer that modulates the local luminal Ca-dependent closure of the SR Ca2+ release channels. At the same time, CASQ2 stabilizes the CICR process by slowing the functional recharging of SR Ca2+ stores. Abnormal restitution of the Ca2+ release channels from a luminal Ca-dependent refractory state could account for ventricular arrhythmias associated with mutations in the CASQ2 gene.

  11. Specific binding of (/sup 3/H)LY186126, an analogue of indolidan (LY195115), to cardiac membranes enriched in sarcoplasmic reticulum vesicles

    Energy Technology Data Exchange (ETDEWEB)

    Kauffman, R.F.; Utterback, B.G.; Robertson, D.W.

    1989-05-01

    LY186126 was found to be a potent inhibitor of type IV cyclic AMP phosphodiesterase located in the sarcoplasmic reticulum of canine cardiac muscle. This compound, a close structural analogue of indolidan (LY195115), was prepared in high specific activity, tritiated form to study the positive inotropic receptor(s) for cardiotonic phosphodiesterase inhibitors such as indolidan and milrinone. A high-affinity binding site for (/sup 3/H)LY186126 was observed (Kd = 4 nM) in purified preparations of canine cardiac sarcoplasmic reticulum vesicles. Binding was proportional to vesicle protein, was inactivated by subjecting membranes to proteolysis or boiling, and was dependent on added Mg2+. Scatchard analysis suggested the presence of a single class of binding sites in the membrane preparation. Indolidan, milrinone, and LY186126 (all at 1 microM) produced essentially complete displacement of bound (/sup 3/H)LY186126, while nifedipine, propranolol, and prazosin had little or no effect at this concentration. This represents the first reported use of a radioactive analogue to label the inotropic receptor for cardiotonic phosphodiesterase inhibitors. The results suggest that (/sup 3/H)LY186126 is a useful radioligand for examining the subcellular site(s) responsible for positive inotropic effects of these drugs.

  12. Size of the plasma membrane H+-ATPase from Neurospora crassa determined by radiation inactivation and comparison with the sarcoplasmic reticulum Ca2+-ATPase from skeletal muscle

    International Nuclear Information System (INIS)

    Bowman, B.J.; Berenski, C.J.; Jung, C.Y.

    1985-01-01

    Using radiation inactivation, the authors have measured the size of the H + -ATPase in Neurospora crassa plasma membranes. Membranes were exposed to either high energy electrons from a Van de Graaff generator or to gamma irradiation from 60 Co. Both forms of radiation caused an exponential loss of ATPase activity in parallel with the physical destruction of the Mr = 104,000 polypeptide of which this enzyme is composed. By applying target theory, the size of the H + -ATPase in situ was found to be approximately 2.3 X 10(5) daltons. They also used radiation inactivation to measure the size of the Ca 2+ -ATPase of sarcoplasmic reticulum and got a value of approximately 2.4 X 10(5) daltons, in agreement with previous reports. By irradiating a mixture of Neurospora plasma membranes and rabbit sarcoplasmic reticulum, they directly compared the sizes of these two ATPases and found them to be essentially the same. The authors conclude that both H + -ATPase and Ca 2+ -ATPase are oligomeric enzymes, most likely composed of two approximately 100,000-dalton polypeptides

  13. Biphasic decay of the Ca transient results from increased sarcoplasmic reticulum Ca leak

    Science.gov (United States)

    Sankaranarayanan, Rajiv; Li, Yatong; Greensmith, David J.; Eisner, David A.

    2016-01-01

    Key points Ca leak from the sarcoplasmic reticulum through the ryanodine receptor (RyR) reduces the amplitude of the Ca transient and slows its rate of decay.In the presence of β‐adrenergic stimulation, RyR‐mediated Ca leak produces a biphasic decay of the Ca transient with a fast early phase and a slow late phase.Two forms of Ca leak have been studied, Ca‐sensitising (induced by caffeine) and non‐sensitising (induced by ryanodine) and both induce biphasic decay of the Ca transient.Only Ca‐sensitising leak can be reversed by traditional RyR inhibitors such as tetracaine.Ca leak can also induce Ca waves. At low levels of leak, waves occur. As leak is increased, first biphasic decay and then slowed monophasic decay is seen. The level of leak has major effects on the shape of the Ca transient. Abstract In heart failure, a reduction in Ca transient amplitude and contractile dysfunction can by caused by Ca leak through the sarcoplasmic reticulum (SR) Ca channel (ryanodine receptor, RyR) and/or decreased activity of the SR Ca ATPase (SERCA). We have characterised the effects of two forms of Ca leak (Ca‐sensitising and non‐sensitising) on calcium cycling and compared with those of SERCA inhibition. We measured [Ca2+]i with fluo‐3 in voltage‐clamped rat ventricular myocytes. Increasing SR leak with either caffeine (to sensitise the RyR to Ca activation) or ryanodine (non‐sensitising) had similar effects to SERCA inhibition: decreased systolic [Ca2+]i, increased diastolic [Ca2+]i and slowed decay. However, in the presence of isoproterenol, leak produced a biphasic decay of the Ca transient in the majority of cells while SERCA inhibition produced monophasic decay. Tetracaine reversed the effects of caffeine but not of ryanodine. When caffeine (1 mmol l−1) was added to a cell which displayed Ca waves, the wave frequency initially increased before waves disappeared and biphasic decay developed. Eventually (at higher caffeine concentrations), the

  14. Impaired sarcoplasmic reticulum Ca(2+) release rate after fatiguing stimulation in rat skeletal muscle

    DEFF Research Database (Denmark)

    Ørtenblad, Niels; Sjøgaard, G; Madsen, Klavs

    2000-01-01

    during the first 0.5-1 h the metabolic state recovered to resting levels, and a slow phase from 1-3 h characterized by a rather slow recovery of the mechanical properties. The recovery of SR Ca(2+) release rate was closely correlated to +dF/dt during the slow phase of recovery (r(2) = 0.51; P ... to 66% that persisted for 1 h, followed by a gradual recovery to 87% of prefatigue release rate at 3 h recovery. Tetanic force and rate of force development (+dF/dt) and relaxation (-dF/dt) were depressed by approximately 80% after stimulation. Recovery occurred in two phases: an initial phase, in which......The purpose of the study was to characterize the sarcoplasmic reticulum (SR) function and contractile properties before and during recovery from fatigue in the rat extensor digitorum longus muscle. Fatiguing contractions (60 Hz, 150 ms/s for 4 min) induced a reduction of the SR Ca(2+) release rate...

  15. Calcium uptake by sarcoplasmic reticulum isolated from hearts of septic rats

    International Nuclear Information System (INIS)

    McDonough, K.H.

    1988-01-01

    Myocardial sarcoplasmic reticulum (SR) plays a critical role in the regulation of the cytosolic calcium fluctuations that occur during the cardiac cycle. One function of the SR is to lower the calcium concentration so that myocardial relaxation and thus ventricular filling can occur. The aim of the present study was to determine if hyperdynamic sepsis induced a decrease in the capacity of SR to take up calcium. This defect would result in decreased ventricular filling and thus decreased cardiac output, as has previously been shown in isolated perfused working hearts removed from septic rats. Therefore, rats were anesthetized with ether, and sepsis was induced by the injection of an aliquot of a fecal homogenate into the peritoneal cavity. Control animals either underwent surgery and received an aliquot of sterilized fecal inoculum (sham) or were untreated (no surgery). On day 2 after surgery, animals were anesthetized with pentobarbital, and hearts were removed, weighted, and SR isolated. The rate of uptake of 45 Ca 2+ by SR from septic rats was not depressed compared to controls but in fact was elevated. Maximum 45 Ca 2+ accumulated by the SR and Ca 2+ -stimulated ATPase activity were similar in SR from control and septic hearts. These results suggest that the contractile dysfunction noted in the myocardium in early sepsis is probably not due to inadequate SR removal of Ca 2+ during diastole

  16. Hofmeister effect of anions on calcium translocation by sarcoplasmic reticulum Ca2+-ATPase

    Science.gov (United States)

    Tadini-Buoninsegni, Francesco; Moncelli, Maria Rosa; Peruzzi, Niccolò; Ninham, Barry W.; Dei, Luigi; Nostro, Pierandrea Lo

    2015-10-01

    The occurrence of Hofmeister (specific ion) effects in various membrane-related physiological processes is well documented. For example the effect of anions on the transport activity of the ion pump Na+, K+-ATPase has been investigated. Here we report on specific anion effects on the ATP-dependent Ca2+ translocation by the sarcoplasmic reticulum Ca2+-ATPase (SERCA). Current measurements following ATP concentration jumps on SERCA-containing vesicles adsorbed on solid supported membranes were carried out in the presence of different potassium salts. We found that monovalent anions strongly interfere with ATP-induced Ca2+ translocation by SERCA, according to their increasing chaotropicity in the Hofmeister series. On the contrary, a significant increase in Ca2+ translocation was observed in the presence of sulphate. We suggest that the anions can affect the conformational transition between the phosphorylated intermediates E1P and E2P of the SERCA cycle. In particular, the stabilization of the E1P conformation by chaotropic anions seems to be related to their adsorption at the enzyme/water and/or at the membrane/water interface, while the more kosmotropic species affect SERCA conformation and functionality by modifying the hydration layers of the enzyme.

  17. Reduced sarcoplasmic reticulum content of releasable Ca2+ in rat soleus muscle fibres after eccentric contractions

    DEFF Research Database (Denmark)

    Nielsen, J S; Sahlin, K; Ørtenblad, N

    2007-01-01

    AIM: The purpose was to evaluate the effects of fatiguing eccentric contractions (EC) on calcium (Ca2+) handling properties in mammalian type I muscles. We hypothesized that EC reduces both endogenous sarcoplasmic reticulum (SR) content of releasable Ca2+ (eSRCa2+) and myofibrillar Ca2+ sensitivity....... METHODS: Isolated rat soleus muscles performed 30 EC bouts. Single fibres were isolated from the muscle and after mechanical removal of sarcolemma used to measure eSRCa2+, rate of SR Ca2+ loading and myofibrillar Ca2+ sensitivity. RESULTS: Following EC maximal force in whole muscle was reduced by 30......% and 16/100 Hz force ratio by 33%. The eSRCa2+ in fibres from non-stimulated muscles was 45 +/- 5% of the maximal loading capacity. After EC, eSRCa2+ per fibre CSA decreased by 38% (P = 0.05), and the maximal capacity of SR Ca2+ loading was depressed by 32%. There were no effects of EC on either...

  18. The amino-terminal 200 amino acids of the plasma membrane Na+,K+-ATPase alpha subunit confer ouabain sensitivity on the sarcoplasmic reticulum Ca(2+)-ATPase.

    OpenAIRE

    Ishii, T; Takeyasu, K

    1993-01-01

    Cardiac glycosides such as G-strophanthin (ouabain) bind to and inhibit the plasma membrane Na+,K(+)-ATPase but not the sarcoplasmic reticulum (SR) Ca(2+)-ATPase, whereas thapsigargin specifically blocks the SR Ca(2+)-ATPase. The chimera [n/c]CC, in which the amino-terminal amino acids Met1 to Asp162 of the SR Ca(2+)-ATPase (SERCA1) were replaced with the corresponding portion of the Na+,K(+)-ATPase alpha 1 subunit (Met1 to Asp200), retained thapsigargin- and Ca(2+)-sensitive ATPase activity,...

  19. Nandrolone decanoate treatment affects sarcoplasmic reticulum Ca(2+) ATPase function in skinned rat slow- and fast-twitch fibres.

    Science.gov (United States)

    Bouhlel, Aicha; Joumaa, Wissam H; Léoty, Claude

    2003-09-01

    The effects of anabolic-androgenic steroid administration on the function of the sarcoplasmic reticulum (SR) pump were investigated in chemically skinned fibres from the extensor digitorum longus (EDL) and soleus muscles of sedentary rats. Twenty male rats were divided into two groups, one group received an intramuscular injection of nandrolone decanoate (15 mg x kg(-1)) weekly for 8 weeks, the second received similar weekly doses of vehicle (sterile peanut oil). Compared with control muscles, nandrolone decanoate treatment reduced SR Ca(2+) loading in EDL and soleus fibres by 49% and 29%, respectively. In control and treated muscles, the rate of Ca(2+) leakage depended on the quantity of Ca(2+) loaded. Furthermore, for similar SR Ca(2+) contents, the Ca(2+) leakage rate was not significantly modified by nandrolone decanoate treatment. Nandrolone decanoate treatment thus affects Ca (2+) uptake by the SR in a fibre-type dependent manner.

  20. Patterns of proteolytic cleavage and carbodiimide derivatization in sarcoplasmic reticulum adenosinetriphosphatase

    International Nuclear Information System (INIS)

    de Ancos, J.G.; Inesi, G.

    1988-01-01

    Two series of experiments were carried out to characterize (a) peptide fragments of sarcoplasmic reticulum (SR) ATPase, based on proteolysis with different enzymes and distribution of known labels, and (b) specific labeling and functional inactivation patterns, following ATPase derivatization with dicyclohexylcarbodiimide (DCCD) under various conditions. Digestion with trypsin or chymotrypsin results in the initial cleavage of the SR ATPase in two fragments of similar size and then into smaller fragments, while subtilisin and thermolysin immediately yield smaller fragments. Peptide fragments were assigned to segments of the protein primary structure and to functionally relevant domains, such as those containing the 32 P at the active site and the fluorescein isothiocyanate at the nucleotide site. ATPase derivatization with [ 14 C]DCCD under mild conditions produced selective inhibition of ATPase hydrolytic catalysis without significant incorporation of the 14 C radioactive label. This effect is attributed to blockage of catalytically active residues by reaction of the initial DCCD adduct with endogenous or exogenous nucleophiles. ATPase derivatization with [ 14 C]DCCD under more drastic conditions produced inhibition of calcium binding, 14 C radioactive labeling of tryptic fragments A 1 and A 2 (but not of B), and extensive cross-linking. The presence of calcium during derivatization prevented functional inactivation, radioactive labeling of fragment A 2 , and internal cross-linking of fragment A 1 . It is proposed that both A 1 and A 2 fragments participate in formation of the calcium binding domain and that the labeled residues of fragment A 2 are directly involved in calcium complexation. A diagram is constructed, representing the relative positions of labels and functional domains within the ATPase protein

  1. Temperature and Ca2+-dependence of the sarcoplasmic reticulum Ca2(+)-ATPase in haddock, salmon, rainbow trout and zebra cichlid

    DEFF Research Database (Denmark)

    Godiksen, Helene; Jessen, Flemming

    2002-01-01

    Temperature dependence of Ca2+-ATPase from the sarcoplasmic reticulum (SR) in rabbit muscle has been widely studied, and it is generally accepted that a break point in Arrhenius plot exist at approximately 20 degreesC. Whether the break point arises as a result of temperature dependent changes......+- ATPase activity. The temperature range of the plateau was 14-21 and 18-25 degreesC in salmon and rainbow trout, respectively. Ca2+-dependence in the four different fish species investigated was very similar with half maximal activation (K-0.5) between 0.2 and 0.6 muM and half maximal inhibition (I-0.......5) between 60 and 250 muM. Results indicated that interaction between SR Ca2+-ATPase and its lipid environment may play an important role for the different Arrhenius plot of the different types of fish species investigated. (C) 2002 Elsevier Science Inc. All rights reserved....

  2. Uncoupling of sarcoplasmic reticulum Ca²⁺-ATPase by N-arachidonoyl dopamine. Members of the endocannabinoid family as thermogenic drugs

    DEFF Research Database (Denmark)

    Mahmmoud, Yasser Ahmed; Gaster, Michel

    2013-01-01

    BACKGROUND AND PURPOSE: The sarcoplasmic reticulum Ca²⁺-ATPase (SERCA) plays a role in thermogenesis. The exogenous compound capsaicin increased SERCA-mediated ATP hydrolysis not coupled to Ca²⁺ transport. Here, we have sought to identify endogenous compounds that may function as SERCA uncoupling...... agents. EXPERIMENTAL APPROACH: Using isolated SR vesicles from rabbits, we have screened for endogenous compounds that uncouple SERCA. We have also studied their ability to deplete cytoplasmic ATP from human skeletal muscle cells in culture. KEY RESULTS: Studies on SR vesicles showed that the endogenous......, regardless of the presence of glucose. CONCLUSIONS AND IMPLICATIONS: NADA is an endogenous molecule that may function as SERCA uncoupling agent in vivo. Members of the endocannabinoid family exert concerted actions on several Ca²⁺-handling proteins. Uncoupling of SERCA by exogenous compounds could be a novel...

  3. pH-modulation of chloride channels from the sarcoplasmic reticulum of skeletal muscle.

    Science.gov (United States)

    Kourie, J I

    1999-01-01

    The understanding of the role of cytoplasmic pH in modulating sarcoplasmic reticulum (SR) ion channels involved in Ca2+ regulation is important for the understanding of the function of normal and adversely affected muscles. The dependency of the SR small chloride (SCl) channel from rabbit skeletal muscle on cytoplasmic pH (pHcis) and luminal pH (pHtrans) was investigated using the lipid bilayer-vesicle fusion technique. Low pHcis 6.75-4.28 modifies the operational mode of this multiconductance channel (conductance levels between 5 and 75 pS). At pHcis 7.26-7.37 the channel mode is dominated by the conductance and kinetics of the main conductance state (65-75 pS) whereas at low pHcis 6.75-4.28 the channel mode is dominated by the conductance and kinetics of subconductance states (5-40 pS). Similarly, low pHtrans 4.07, but not pHtrans 6.28, modified the activity of SCl channels. The effects of low pHcis are pronounced at 10(-3) and 10(-4) M [Ca2+]cis but are not apparent at 10(-5) M [Ca2+]cis, where the subconductances of the channel are already prominent. Low pHcis-induced mode shift in the SCl channel activity is due to modification of the channel proteins that cause the uncoupling of the subconductance states. The results in this study suggest that low pHcis can modify the functional properties of the skeletal SR ion channels and hence contribute, at least partly, to the malfunction in the contraction-relaxation mechanism in skeletal muscle under low cytoplasmic pH levels.

  4. Roles of phosphorylation and nucleotide binding domains in calcium transport by sarcoplasmic reticulum adenosinetriphosphatase

    International Nuclear Information System (INIS)

    Teruel, J.A.; Inesi, G.

    1988-01-01

    The roles of the phosphorylation (phosphorylated enzyme intermediate) and nucleotide binding domains in calcium transport were studied by comparing acetyl phosphate and ATP as substrates for the Ca 2+ -ATPase of sarcoplasmic reticulum vesicles. The authors found that the maximal level of phosphoenzyme obtained with either substrate is approximately 4 nmol/mg of protein, corresponding to the stoichiometry of catalytic sites in their preparation. The initial burst of phosphoenzyme formation observed in the transient state, following addition of either substrate, is accompanied by internalization of 2 mol of calcium per mole of phosphoenzyme. The internalized calcium is then translocated with a sequential pattern, independent of the substrate used. Following a rate-limiting step, the phosphoenzyme undergoes hydrolytic cleavage and proceeds to the steady-state activity which is soon back inhibited by the rise of Ca 2+ concentration in the lumen of the vesicles. When the back inhibition is released by the addition of oxalate, substrate utilization and calcium transport occur with a ratio of 1:2, independent of the substrate and its concentration. When the nucleotide binding site is derivatized with FITP, the enzyme can still utilize acetyl phosphate (but not ATP) for calcium transport. These observations demonstrate that the basic coupling mechanism of catalysis and calcium transport involves the phosphorylation and calcium binding domains, and not the nucleotide binding domain. On the other hand, occupancy of the FITC-sensitive nucleotide site is involved in kinetic regulation not only with respect to utilization of substrate for the phosphoryl transfer reaction but also for subsequent steps related to calcium translocation and phosphoenzyme turnover

  5. Characterization of detergent-solubilized sarcoplasmic reticulum Ca2+-ATPase by high-performance liquid chromatography

    International Nuclear Information System (INIS)

    Andersen, J.P.; Vilsen, B.; Nielsen, H.; Moller, J.V.

    1986-01-01

    Sarcoplasmic reticulum Ca 2+ -ATPase solubilized by the nonionic detergent octaethylene glycol monododecyl ether was studied by molecular sieve high-performance liquid chromatography (HPLC) and analytical ultracentrifugation. Significant irreversible aggregation of soluble Ca 2+ -ATPase occurred within a few hours in the presence of ≤ 50 μM Ca 2+ . The aggregates were inactive and were primarily held together by hydrophobic forces. In the absence of reducing agent, secondary formation of disulfide bonds occurred. The stability of the inactive dimer upon dilution permitted unambiguous assignment of its elution position and sedimentation coefficient. At high 45 Ca 2+ concentration (500 μM), monomeric Ca 2+ -ATPase was stable for several house. Reversible self-association induced by variation in protein, detergent, and lipid concentrations was studied by large-zone HPLC. The association constant for dimerization of active Ca 2+ -ATPase was found to be 10 5 -10 6 M -1 depending on the detergent concentration. More detergent was bound to monomeric than to dimeric Ca 2+ -ATPase, even above the critical micellar concentration of the detergent. Binding of Ca 2+ and 48 V vanadate as well as ATP-dependent phosphorylation was studied in monomeric and in reversibly associated dimeric preparations. In both forms, two high-affinity Ca 2+ binding sites per phosphorylation site existed. The delipidated monomer purified by HPLC was able to form ADP-insensitive phosphoenzyme and to bind ATP and vanadate simultaneously. The results suggest that formation of Ca 2+ -ATPase oligomers in the membrane is governed by nonspecific forces (low affinity) and that each polypeptide chain constitutes a functional unit

  6. Comparison of the calcium release channel of cardiac and skeletal muscle sarcoplasmic reticulum by target inactivation analysis

    International Nuclear Information System (INIS)

    McGrew, S.G.; Inui, Makoto; Chadwick, C.C.; Boucek, R.J. Jr.; Jung, C.Y.; Fleischer, S.

    1989-01-01

    The calcium release channel of sarcoplasmic reticulum which triggers muscle contraction in excitation-contraction coupling has recently been isolated. The channel has been found to be morphologically identical with the feet structures of the junctional face membrane of terminal cisternae and consists of an oligomer of a unique high molecular weight polypeptide. In this study, the authors compare the target size of the calcium release channel from heart and skeletal muscle using target inactivation analysis. The target molecular weights of the calcium release channel estimated by measuring ryanodine binding after irradiation are similar for heart (139,000) and skeletal muscle (143,000) and are smaller than the monomeric unit (estimated to be about 360,000). The target size, estimated by measuring polypeptide remaining after irradiation, was essentially the same for heart and skeletal muscle, 1,061,000 and 1,070,000, respectively, indicating an oligomeric association of protomers. Thus, the calcium release channel of both cardiac and skeletal muscle reacts uniquely with regard to target inactivation analysis in that (1) the size by ryanodine binding is smaller than the monomeric unit and (2) a single hit leads to destruction of more than one polypeptide, by measuring polypeptide remaining. The target inactivation analysis studies indicate that heart and skeletal muscle receptors are structurally very similar

  7. Effect of triorganotin compounds on calcium transport mechanisms in rat cardiac sarcoplasmic reticulum

    International Nuclear Information System (INIS)

    Cameron, J.A.; Kodavanti, P.R.S.; Yallapragada, P.R.; Desaiah, D.

    1990-01-01

    Although organotin compounds, in general, are neurotoxicants, recent studies indicate that these tin compounds affect heme metabolism as well as cardiovascular system. Sarcoplasmic reticulum (SR) calcium pump together with phosphorylation of phospholamban has an important role in myocardial contraction and relaxation. Since organotin compounds interfere with cardiovascular system, we have studied the in vitro as well as in vivo effects of tributyltin bromide (TBT), triethyltin bromide (TET) and trimethyltin chloride (TMT) on cardiac SR Ca 2+ -pump activity, in order to know the relative potency of these tin compounds. SR was isolated from heart ventricles of male Sprague-Dawley rats and used for in vitro studies. For in vivo studies, rats were treated orally in corn oil for 6 days with different doses of TET (0.5, 1.0 and 1.5 mg/kg/d), TMT (0.75, 1.5 and 2.5 mg/kg/d) and TBT (0.75, 1.5 and 2.5 mg/kg/d). Rats were sacrificed 24 hr after the last dosage and cardiac SR was prepared. Cardiac SR Ca 2+ -ATPase and 45 Ca-uptake were measured. All the three tin compounds inhibited Ca 2+ -ATPase and 45 Ca-uptake in vitro in a concentration dependent manner. The order of potency for Ca 2+ -ATPase as determined IC 50 , is TBT (2 uM) > TET (63 uM) > TMT (280 uM). For 45 Ca-uptake, if followed the same order i.e., TBT (0.35 uM) > TET (10 uM) > TMT (440 uM). In agreement with in vitro results, both SR Ca 2+ -ATPase and 45 Ca-uptake were significantly inhibited in rats treated with these tin compounds. These studies indicate that triorganotin compounds affect Ca 2+ -pumping mechanisms and thereby alter cardiac contraction-relaxation process

  8. N-acetylcysteine fails to modulate the in vitro function of sarcoplasmic reticulum of diaphragm in the final phase of fatigue.

    Science.gov (United States)

    Mishima, T; Yamada, T; Matsunaga, S; Wada, M

    2005-07-01

    In the present study, we tested the hypothesis whether N-acetylcysteine (NAC), a non-specific antioxidant, might influence fatigue by modulating Ca2+-handling capacity by the sarcoplasmic reticulum (SR). In the presence (10 mm) or absence of NAC, bundles of rat diaphragm were stimulated with tetanic trains (350 ms, 30-40 Hz) at 1 train every 2 s for 300 s. SR functions, as assessed by SR Ca2+-uptake and release rates and SR Ca2+-ATPase activity, were measured in vitro on muscle homogenates. Following the 300-s stimulation, the force developed by NAC-treated muscles is approximately 1.8-fold higher (P depression in SR function (P < 0.05). Despite the differing degrees of fatigue between NAC-treated and non-treated muscles, SR functions in these muscles were reduced to similar extents. These results suggest that modulation of SR function measured in vitro may not be a major contributor to inhibition of diaphragmic fatigue with antioxidant, at least, in the final phase of fatigue where force output is remarkably reduced.

  9. Presence of a Ca2+-sensitive CDPdiglyceride-inositol transferase in canine cardiac sarcoplasmic reticulum

    International Nuclear Information System (INIS)

    Kasinathan, C.; Kirchberger, M.A.

    1988-01-01

    Sarcoplasmic reticulum (SR) and plasma membranes from canine left ventricle were used to evaluate the presence of the enzyme CDPdiglyceride-inositol transferase in these membranes. (K + ,-Ca 2+ )-ATPase activity, a marker for SR, was 79.2 +/- 5.0 (SE) and 11.2 +/- 2.0 μmol x mg -1 x h -1 in SR and plasma membrane preparations, respectively, and (Na + , K + )-ATPase activity, a marker for plasma membranes, was 5.6 +/- 1.2 and 99.2 +/- 8.0 μmol x mg -1 x h -1 , respectively. Contamination of SR and plasma membrane preparations by mitochondria was estimated to be 2% and 8%, respectively, and by Golgi membranes, 0.9% and 1.8%, respectively. The transferase activity detected in the plasma membrane preparation could be accounted for largely, but not entirely, by contaminating SR membranes. The pH optimum for the SR transferase activity was between 8.0 and 9.0. Ca 2+ inhibited the enzyme, half-maximal inhibition occurring at about 10 μM Ca 2+ . No loss of [ 3 H]PtdIns could be detected when membranes were incubated in the presence or absence of Ca 2+ . The Ca 2+ inhibition of the transferase was noncompetitive with respect to CDP-dipalmitin while that with respect to myo-inositol was slightly noncompetitive at low [Ca 2+ ] and became uncompetitive at higher [Ca 2+ ]. It is concluded that CDPdiglyceride-inositol transferase is present on SR membranes and is sensitive to micromolar Ca 2+ . The data are consistent with a putative role for the inhibition of the SR transferase by Ca 2+ and acidic pH in the protection of the SR against calcium overload in ischemic myocardium

  10. Inhibition of sarcoplasmic reticulum Ca(2+)-ATPase decreases atrioventricular node-paced heart rate in rabbits.

    Science.gov (United States)

    Cheng, Hongwei; Smith, Godfrey L; Orchard, Clive H; Hancox, Jules C; Burton, Francis L

    2012-10-01

    Recent data indicate that Ca(2+) cycling in isolated atrioventricular node (AVN) cells contributes to setting spontaneous rate. The aim of the present study was to extend this observation to the intact AVN in situ, by evaluating the effects of inhibiting sarcoplasmic reticulum Ca(2+) uptake with cyclopiazonic acid (CPA) on intact AVN spontaneous activity and its response to isoprenaline. A model of the AVN-paced heart was produced to investigate intact AVN automaticity, by surgical ablation of the sino-atrial node (SAN) in the rabbit Langendorff-perfused heart. Electrograms were recorded from a site close to the AVN (triangle of Koch), an atrial site above the AVN, the left atrium and right ventricle, enabling AVN pacing of the preparation to be confirmed. Before SAN ablation, the heart rate was 166.8 ± 5.4 beats min(-1). Ablation of the SAN was clearly indicated by a sudden and significant decrease of heart rate to 108.6 ± 9.6 beats min(-1) (P AVN rate to 187.8 ± 12.0 beats min(-1) after 1 min of application (P AVN rate to 81.6 ± 4.8 (n = 9) and 77.4 ± 6.0 beats min(-1) (n = 7), respectively [P AVN rate increase in response to isoprenaline from 78.8 ± 10.0 to 46.8 ± 6.8 and 26.7 ± 5.3%, respectively (P AVN rate and its response to isoprenaline indicate that Ca(2+) cycling is important to the intact AVN spontaneous activity and its acceleration during sympathetic stimulation.

  11. Crosstalk between mitochondrial and sarcoplasmic reticulum Ca2+ cycling modulates cardiac pacemaker cell automaticity.

    Directory of Open Access Journals (Sweden)

    Yael Yaniv

    Full Text Available Mitochondria dynamically buffer cytosolic Ca(2+ in cardiac ventricular cells and this affects the Ca(2+ load of the sarcoplasmic reticulum (SR. In sinoatrial-node cells (SANC the SR generates periodic local, subsarcolemmal Ca(2+ releases (LCRs that depend upon the SR load and are involved in SANC automaticity: LCRs activate an inward Na(+-Ca(2+ exchange current to accelerate the diastolic depolarization, prompting the ensemble of surface membrane ion channels to generate the next action potential (AP.To determine if mitochondrial Ca(2+ (Ca(2+ (m, cytosolic Ca(2+ (Ca(2+ (c-SR-Ca(2+ crosstalk occurs in single rabbit SANC, and how this may relate to SANC normal automaticity.Inhibition of mitochondrial Ca(2+ influx into (Ru360 or Ca(2+ efflux from (CGP-37157 decreased [Ca(2+](m to 80 ± 8% control or increased [Ca(2+](m to 119 ± 7% control, respectively. Concurrent with inhibition of mitochondrial Ca(2+ influx or efflux, the SR Ca(2+ load, and LCR size, duration, amplitude and period (imaged via confocal linescan significantly increased or decreased, respectively. Changes in total ensemble LCR Ca(2+ signal were highly correlated with the change in the SR Ca(2+ load (r(2 = 0.97. Changes in the spontaneous AP cycle length (Ru360, 111 ± 1% control; CGP-37157, 89 ± 2% control in response to changes in [Ca(2+](m were predicted by concurrent changes in LCR period (r(2 = 0.84.A change in SANC Ca(2+ (m flux translates into a change in the AP firing rate by effecting changes in Ca(2+ (c and SR Ca(2+ loading, which affects the characteristics of spontaneous SR Ca(2+ release.

  12. Altered sarco(endo)plasmic reticulum calcium adenosine triphosphatase 2a content: Targets for heart failure therapy.

    Science.gov (United States)

    Liu, Gang; Li, Si Qi; Hu, Ping Ping; Tong, Xiao Yong

    2018-05-01

    Sarco(endo)plasmic reticulum calcium adenosine triphosphatase is responsible for transporting cytosolic calcium into the sarcoplasmic reticulum and endoplasmic reticulum to maintain calcium homeostasis. Sarco(endo)plasmic reticulum calcium adenosine triphosphatase is the dominant isoform expressed in cardiac tissue, which is regulated by endogenous protein inhibitors, post-translational modifications, hormones as well as microRNAs. Dysfunction of sarco(endo)plasmic reticulum calcium adenosine triphosphatase is associated with heart failure, which makes sarco(endo)plasmic reticulum calcium adenosine triphosphatase a promising target for heart failure therapy. This review summarizes current approaches to ameliorate sarco(endo)plasmic reticulum calcium adenosine triphosphatase function and focuses on phospholamban, an endogenous inhibitor of sarco(endo)plasmic reticulum calcium adenosine triphosphatase, pharmacological tools and gene therapies.

  13. Interaction between endoplasmic/sarcoplasmic reticulum stress (ER/SR stress), mitochondrial signaling and Ca(2+) regulation in airway smooth muscle (ASM).

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    Delmotte, Philippe; Sieck, Gary C

    2015-02-01

    Airway inflammation is a key aspect of diseases such as asthma. Several inflammatory cytokines (e.g., TNFα and IL-13) increase cytosolic Ca(2+) ([Ca(2+)]cyt) responses to agonist stimulation and Ca(2+) sensitivity of force generation, thereby enhancing airway smooth muscle (ASM) contractility (hyper-reactive state). Inflammation also induces ASM proliferation and remodeling (synthetic state). In normal ASM, the transient elevation of [Ca(2+)]cyt induced by agonists leads to a transient increase in mitochondrial Ca(2+) ([Ca(2+)]mito) that may be important in matching ATP production with ATP consumption. In human ASM (hASM) exposed to TNFα and IL-13, the transient increase in [Ca(2+)]mito is blunted despite enhanced [Ca(2+)]cyt responses. We also found that TNFα and IL-13 induce reactive oxidant species (ROS) formation and endoplasmic/sarcoplasmic reticulum (ER/SR) stress (unfolded protein response) in hASM. ER/SR stress in hASM is associated with disruption of mitochondrial coupling with the ER/SR membrane, which relates to reduced mitofusin 2 (Mfn2) expression. Thus, in hASM it appears that TNFα and IL-13 result in ROS formation leading to ER/SR stress, reduced Mfn2 expression, disruption of mitochondrion-ER/SR coupling, decreased mitochondrial Ca(2+) buffering, mitochondrial fragmentation, and increased cell proliferation.

  14. Ryanodine receptor fragmentation and sarcoplasmic reticulum Ca2+ leak after one session of high-intensity interval exercise.

    Science.gov (United States)

    Place, Nicolas; Ivarsson, Niklas; Venckunas, Tomas; Neyroud, Daria; Brazaitis, Marius; Cheng, Arthur J; Ochala, Julien; Kamandulis, Sigitas; Girard, Sebastien; Volungevičius, Gintautas; Paužas, Henrikas; Mekideche, Abdelhafid; Kayser, Bengt; Martinez-Redondo, Vicente; Ruas, Jorge L; Bruton, Joseph; Truffert, Andre; Lanner, Johanna T; Skurvydas, Albertas; Westerblad, Håkan

    2015-12-15

    High-intensity interval training (HIIT) is a time-efficient way of improving physical performance in healthy subjects and in patients with common chronic diseases, but less so in elite endurance athletes. The mechanisms underlying the effectiveness of HIIT are uncertain. Here, recreationally active human subjects performed highly demanding HIIT consisting of 30-s bouts of all-out cycling with 4-min rest in between bouts (≤3 min total exercise time). Skeletal muscle biopsies taken 24 h after the HIIT exercise showed an extensive fragmentation of the sarcoplasmic reticulum (SR) Ca(2+) release channel, the ryanodine receptor type 1 (RyR1). The HIIT exercise also caused a prolonged force depression and triggered major changes in the expression of genes related to endurance exercise. Subsequent experiments on elite endurance athletes performing the same HIIT exercise showed no RyR1 fragmentation or prolonged changes in the expression of endurance-related genes. Finally, mechanistic experiments performed on isolated mouse muscles exposed to HIIT-mimicking stimulation showed reactive oxygen/nitrogen species (ROS)-dependent RyR1 fragmentation, calpain activation, increased SR Ca(2+) leak at rest, and depressed force production due to impaired SR Ca(2+) release upon stimulation. In conclusion, HIIT exercise induces a ROS-dependent RyR1 fragmentation in muscles of recreationally active subjects, and the resulting changes in muscle fiber Ca(2+)-handling trigger muscular adaptations. However, the same HIIT exercise does not cause RyR1 fragmentation in muscles of elite endurance athletes, which may explain why HIIT is less effective in this group.

  15. Ryanodine receptor fragmentation and sarcoplasmic reticulum Ca2+ leak after one session of high-intensity interval exercise

    Science.gov (United States)

    Place, Nicolas; Ivarsson, Niklas; Venckunas, Tomas; Neyroud, Daria; Brazaitis, Marius; Cheng, Arthur J.; Ochala, Julien; Kamandulis, Sigitas; Girard, Sebastien; Volungevičius, Gintautas; Paužas, Henrikas; Mekideche, Abdelhafid; Kayser, Bengt; Martinez-Redondo, Vicente; Bruton, Joseph; Truffert, Andre; Lanner, Johanna T.; Skurvydas, Albertas; Westerblad, Håkan

    2015-01-01

    High-intensity interval training (HIIT) is a time-efficient way of improving physical performance in healthy subjects and in patients with common chronic diseases, but less so in elite endurance athletes. The mechanisms underlying the effectiveness of HIIT are uncertain. Here, recreationally active human subjects performed highly demanding HIIT consisting of 30-s bouts of all-out cycling with 4-min rest in between bouts (≤3 min total exercise time). Skeletal muscle biopsies taken 24 h after the HIIT exercise showed an extensive fragmentation of the sarcoplasmic reticulum (SR) Ca2+ release channel, the ryanodine receptor type 1 (RyR1). The HIIT exercise also caused a prolonged force depression and triggered major changes in the expression of genes related to endurance exercise. Subsequent experiments on elite endurance athletes performing the same HIIT exercise showed no RyR1 fragmentation or prolonged changes in the expression of endurance-related genes. Finally, mechanistic experiments performed on isolated mouse muscles exposed to HIIT-mimicking stimulation showed reactive oxygen/nitrogen species (ROS)-dependent RyR1 fragmentation, calpain activation, increased SR Ca2+ leak at rest, and depressed force production due to impaired SR Ca2+ release upon stimulation. In conclusion, HIIT exercise induces a ROS-dependent RyR1 fragmentation in muscles of recreationally active subjects, and the resulting changes in muscle fiber Ca2+-handling trigger muscular adaptations. However, the same HIIT exercise does not cause RyR1 fragmentation in muscles of elite endurance athletes, which may explain why HIIT is less effective in this group. PMID:26575622

  16. Altered calcium pump and secondary deficiency of γ-sarcoglycan and microspan in sarcoplasmic reticulum membranes isolated from δ-sarcoglycan knockout mice

    Science.gov (United States)

    Solares-Pérez, Alhondra; Álvarez, Rocío; Crosbie, Rachelle H.; Vega-Moreno, Jesús; Medina-Monares, Joel; Estrada, Francisco J.; Ortega, Alicia; Coral-Vazquez, Ramón

    2016-01-01

    Sarcoglycans (SGs) and sarcospan (SSPN) are transmembrane proteins of the dystrophin-glycoprotein complex. Mutations in the genes encoding SGs cause many inherited forms of muscular dystrophy. In this study, using purified membranes of wild-type (WT) and δ-SG knockout (KO) mice, we found the specific localization of the SG-SSPN isoforms in transverse tubules (TT) and sarcoplasmic reticulum (SR) membranes. Immunoblotting revealed that the absence of δ-SG isoforms in TT and SR results in a secondary deficiency of γ-SG and µSPN. Our results showed augmented ATP hydrolytic activity, ATP-dependent calcium uptake and passive calcium efflux, probably through SERCA1 in KO compared to WT mice. Furthermore, we found a conformational change in SERCA1 isolated from KO muscle as demonstrated by calorimetric analysis. Following these alterations with mechanical properties, we found an increase in force in KO muscle with the same rate of fatigue but with a decreased fatigue recovery compared to WT. Together our observations suggest, for the first time, that the δ-SG isoforms may stabilize the expression of γ-SG and µSPN in the TT and SR membranes and that this possible complex may play a role in the maintenance of a stable level of resting cytosolic calcium concentration in skeletal muscle. PMID:20638123

  17. Phospholipid alterations in cardiac sarcoplasmic reticulum induced by xanthine oxidase: contamination of commercial preparations of xanthine oxidase by phospholipase A2

    International Nuclear Information System (INIS)

    Gamache, D.A.; Kornberg, L.J.; Bartolf, M.; Franson, R.C.

    1986-01-01

    Incubation of cardiac sarcoplasmic reticulum with xanthine oxidase alone at pH 7.0 resulted in a loss of lipid phosphorus that was potentiated by the addition of xanthine. Using autoclaved E.coli with 1- 14 C-oleate in the 2-acyl position of membrane phospholipids, the authors demonstrate that many, but not all, commercial preparations of xanthine oxidase contain significant phospholipase A 2 (PLA 2 ) activity (64.3-545.6 nmols/min/mg). The PLA 2 was maximally active in the neutral-alkaline pH range, was Ca 2+ -dependent, and was unaffected by the addition of xanthine. PLA 2 activity was totally inhibited by 1mM EDTA whereas radical production by optimal concentrations of xanthine/xanthine oxidase (X/XO) was unaffected by EDTA. Chromatographically purified xanthine oxidase (Sigma Grade III) contained high levels of PLA 2 activity (64.3 nmols/min/mg) compared to endogenous levels of neutral-active, Ca 2+ -dependent PLA 2 measured in various tissue homogenates (≤ 0.5 nmols/ min/mg). Because X/XO mixtures are used extensively to study oxygen free radical-induced cell injury and membrane phospholipid alterations, the presence of a potent extracellular PLA 2 may have influenced previously published reports, and such studies should be interpreted cautiously

  18. Decrease in sarcoplasmic reticulum calcium content, not myofilament function, contributes to muscle twitch force decline in isolated cardiac trabeculae

    Science.gov (United States)

    Milani-Nejad, Nima; Brunello, Lucia; Gyorke, Sándor; Janssen, Paul M.L.

    2014-01-01

    We set out to determine the factors responsible for twitch force decline in isolated intact rat cardiac trabeculae. The contractile force of trabeculae declined over extended periods of isometric twitch contractions. The force-frequency relationship within the frequency range of 4–8 Hz, at 37 °C, became more positive and the frequency optimum shifted to higher rates with this decline in baseline twitch tensions. The post-rest potentiation (37 °C), a phenomenon highly dependent on calcium handling mechanisms, became more pronounced with decrease in twitch tensions. We show that the main abnormality during muscle run-down was not due to a deficit in the myofilaments; maximal tension achieved using a K+ contracture protocol was either unaffected or only slightly decreased. Conversely, the sarcoplasmic reticulum (SR) calcium content, as assessed by rapid cooling contractures (from 27 °C to 0 °C), decreased, and had a close association with the declining twitch tensions (R2 ~ 0.76). SR Ca2+-ATPase, relative to Na+/Ca2+ exchanger activity, was not altered as there was no significant change in paired rapid cooling contracture ratios. Furthermore, confocal microscopy detected no abnormalities in the overall structure of the cardiomyocytes and t-tubules in the cardiac trabeculae (~23 °C). Overall, the data indicates that the primary mechanism responsible for force run-down in multi-cellular cardiac preparations is a decline in the SR calcium content and not the maximal tension generation capability of the myofilaments. PMID:25056841

  19. Dynamic measurement of the calcium buffering properties of the sarcoplasmic reticulum in mouse skeletal muscle.

    Science.gov (United States)

    Manno, Carlo; Sztretye, Monika; Figueroa, Lourdes; Allen, Paul D; Ríos, Eduardo

    2013-01-15

    The buffering power, B, of the sarcoplasmic reticulum (SR), ratio of the changes in total and free [Ca(2+)], was determined in fast-twitch mouse muscle cells subjected to depleting membrane depolarization. Changes in total SR [Ca(2+)] were measured integrating Ca(2+) release flux, determined with a cytosolic [Ca(2+)] monitor. Free [Ca(2+)](SR) was measured using the cameleon D4cpv-Casq1. In 34 wild-type (WT) cells average B during the depolarization (ON phase) was 157 (SEM 26), implying that of 157 ions released, 156 were bound inside the SR. B was significantly greater when BAPTA, which increases release flux, was present in the cytosol. B was greater early in the pulse - when flux was greatest - than at its end, and greater in the ON than in the OFF. In 29 Casq1-null cells, B was 40 (3.6). The difference suggests that 75% of the releasable calcium is normally bound to calsequestrin. In the nulls the difference in B between ON and OFF was less than in the WT but still significant. This difference and the associated decay in B during the ON were not artifacts of a slow SR monitor, as they were also found in the WT when [Ca(2+)](SR) was tracked with the fast dye fluo-5N. The calcium buffering power, binding capacity and non-linear binding properties of the SR measured here could be accounted for by calsequestrin at the concentration present in mammalian muscle, provided that its properties were substantially different from those found in solution. Its affinity should be higher, or K(D) lower than the conventionally accepted 1 mm; its cooperativity (n in a Hill fit) should be higher and the stoichiometry of binding should be at the higher end of the values derived in solution. The reduction in B during release might reflect changes in calsequestrin conformation upon calcium loss.

  20. Matching of sarcoplasmic reticulum and contractile properties in rat fast- and slow-twitch muscle fibres.

    Science.gov (United States)

    Trinh, Huong H; Lamb, Graham D

    2006-07-01

    1. The twitch characteristics (fast-twitch or slow-twitch) of skeletal muscle fibres are determined not only by the contractile apparatus properties of the fibre, but also by the time-course of Ca2+ release and re-uptake by the sarcoplasmic reticulum (SR). The present study examined, in individual fibres from non-transforming muscle of the rat, whether particular SR properties are matched to the contractile apparatus properties of the fibre, in particular in the case of fibres with fast-twitch contractile apparatus located in a slow-twitch muscle, namely the soleus. 2. Force was recorded in single, mechanically skinned fibres from extensor digitorum longus (EDL), gastrocnemius, peroneus longus and soleus muscles. Using repeated cycles in which the SR was emptied of all releasable Ca2+ and then reloaded, it was possible to determine the relative amount of Ca2+ present in the SR endogenously, the maximum SR capacity and the rate of Ca2+ loading. The sensitivity of the contractile apparatus to Ca2+ and Sr2+ was used to classify the fibres as fast-twitch (FT), slow-twitch (ST) or mixed (fibres examined) and thereby identify the likely troponin C and myosin heavy chain types present. 3. There was no significant difference in SR properties between the groups of FT fibres obtained from the four different muscles, including soleus. Despite some overlap in the SR properties of individual fibres between the FT and ST groups, the properties of the FT fibres in all four muscles studied were significantly different from those of the ST and mixed fibres. 4. In general, in FT fibres the SR had a larger capacity and the endogenous Ca2+ content was a relatively lower percentage of maximum compared with ST fibres. Importantly, in terms of their SR properties, FT fibres from soleus muscle more closely resembled FT fibres from other muscles than they did ST fibres from soleus muscle.

  1. The protein phosphatase-1/inhibitor-2 complex differentially regulates GSK3 dephosphorylation and increases sarcoplasmic/endoplasmic reticulum calcium ATPase 2 levels

    International Nuclear Information System (INIS)

    King, Taj D.; Gandy, Johanna C.; Bijur, Gautam N.

    2006-01-01

    The ubiquitously expressed protein glycogen synthase kinase-3 (GSK3) is constitutively active, however its activity is markedly diminished following phosphorylation of Ser21 of GSK3α and Ser9 of GSK3β. Although several kinases are known to phosphorylate Ser21/9 of GSK3, for example Akt, relatively much less is known about the mechanisms that cause the dephosphorylation of GSK3 at Ser21/9. In the present study KCl-induced plasma membrane depolarization of SH-SY5Y cells, which increases intracellular calcium concentrations caused a transient decrease in the phosphorylation of Akt at Thr308 and Ser473, and GSK3 at Ser21/9. Overexpression of the selective protein phosphatase-1 inhibitor protein, inhibitor-2, increased basal GSK3 phosphorylation at Ser21/9 and significantly blocked the KCl-induced dephosphorylation of GSK3β, but not GSK3α. The phosphorylation of Akt was not affected by the overexpression of inhibitor-2. GSK3 activity is known to affect sarcoplasmic/endoplasmic reticulum calcium ATPase 2 (SERCA2) levels. Overexpression of inhibitor-2 or treatment of cells with the GSK3 inhibitors lithium and SB216763 increased the levels of SERCA2. These results indicate that the protein phosphatase-1/inhibitor-2 complex differentially regulates GSK3 dephosphorylation induced by KCl and that GSK3 activity regulates SERCA2 levels

  2. The role of the sarcoplasmic reticulum in the generation of high heart rates and blood pressures in reptiles.

    Science.gov (United States)

    Galli, Gina L J; Gesser, Hans; Taylor, Edwin W; Shiels, Holly A; Wang, Tobias

    2006-05-01

    The functional significance of the sarcoplasmic reticulum (SR) in the generation of high heart rates and blood pressures was investigated in four species of reptile; the turtle, Trachemys scripta; the python, Python regius, the tegu lizard, Tupinanvis merianae, and the varanid lizard, Varanus exanthematicus. Force-frequency trials and imposed pauses were performed on ventricular and atrial tissue from each species with and without the SR inhibitor ryanodine, and in the absence and presence of adrenaline. In all species, an imposed pause of 1 or 5 min caused a post-rest decay of force, and a negative force-frequency response was observed in all species within their in vivo frequency range of heart rates. These relationships were not affected by either ryanodine or adrenaline. In ventricular strips from varanid lizards and pythons, ryanodine caused significant reductions in twitch force within their physiologically relevant frequency range. In atrial tissue from the tegu and varanid lizards, SR inhibition reduced twitch force across the whole of their physiological frequency range. In contrast, in the more sedentary species, the turtle and the python, SR inhibition only decreased twitch force at stimulation frequencies above maximal in vivo heart rates. Adrenaline caused an increase in twitch force in all species studied. In ventricular tissue, this positive inotropic effect was sufficient to overcome the negative effects of ryanodine. In atrial tissue however, adrenaline could only ameliorate the negative effects of ryanodine at the lower pacing frequencies. Our results indicate that reptiles recruit Ca2+ from the SR for force development in a frequency and tissue dependent manner. This is discussed in the context of the development of high reptilian heart rates and blood pressures.

  3. Effects of dantrolene and its derivatives on Ca2+ release from the sarcoplasmic reticulum of mouse skeletal muscle fibres

    Science.gov (United States)

    Ikemoto, Takaaki; Hosoya, Takamitsu; Aoyama, Hiroshi; Kihara, Yasutaka; Suzuki, Masaaki; Endo, Makoto

    2001-01-01

    We analysed the effect of dantrolene (Dan) and five newly synthesized derivatives (GIFs) on Ca2+ release from the sarcoplasmic reticulum (SR) of mouse skeletal muscle.In intact muscles, GIF-0185 reduced the size of twitch contraction induced by electrical stimulation to the same extent as Dan. GIF-0082, an azido-functionalized Dan derivative, also inhibited twitch contraction, although the extent of inhibition was less than that of Dan and of GIF-0185.In skinned fibres, Dan inhibited Ca2+-induced Ca2+ release (CICR) under Mg2+-free conditions at room temperature. In contrast, GIF-0082 and GIF-0185 showed no inhibitory effect on CICR under the same conditions.Dan-induced inhibition of CICR was not affected by the presence of GIF-0082, whereas it was diminished in the presence of GIF-0185.GIF-0082 and GIF-0185 significantly inhibited clofibric acid (Clof)-induced Ca2+ release, as did Dan.Several Dan derivatives other than GIF-0082 and GIF-0185 showed an inhibitory effect on twitch tension but not on the CICR mechanism. All of these derivatives inhibited Clof-induced Ca2+ release.The magnitudes of inhibition of Clof-induced Ca2+ release by all Dan derivatives were well correlated with those of twitch inhibition. This supports the notion that the mode of Clof-induced opening of the RyR-Ca2+ release channel may be similar to that of physiological Ca2+ release (PCR).These results indicate that the difference in opening modes of the RyR-Ca2+ release channel is recognized by certain Dan derivatives. PMID:11606312

  4. Sarcoplasmic reticulum calcium release compared in slow-twitch and fast-twitch fibres of mouse muscle.

    Science.gov (United States)

    Baylor, S M; Hollingworth, S

    2003-08-15

    Experiments were carried out to compare the amplitude and time course of Ca2+ release from the sarcoplasmic reticulum (SR) in intact slow-twitch and fast-twitch mouse fibres. Individual fibres within small bundles were injected with furaptra, a low-affinity, rapidly responding Ca2+ indicator. In response to a single action potential at 16 degrees C, the peak amplitude and half-duration of the change in myoplasmic free [Ca2+] (Delta[Ca2+]) differed significantly between fibre types (slow-twitch: peak amplitude, 9.4 +/- 1.0 microM (mean +/- S.E.M.); half-duration, 7.7 +/- 0.6 ms; fast-twitch: peak amplitude 18.5 +/- 0.5 microM; half-duration, 4.9 +/- 0.3 ms). SR Ca2+ release was estimated from Delta[Ca2+] with a computational model that calculated Ca2+ binding to the major myoplasmic Ca2+ buffers (troponin, ATP and parvalbumin); buffer concentrations and reaction rate constants were adjusted to reflect fibre-type differences. In response to an action potential, the total concentration of released Ca2+ (Delta[CaT]) and the peak rate of Ca2+ release ((d/dt)Delta[CaT]) differed about 3-fold between the fibre types (slow-twitch: Delta[CaT], 127 +/- 7 microM; (d/dt)Delta[CaT], 70 +/- 6 microM ms-1; fast-twitch: Delta[CaT], 346 +/- 6 microM; (d/dt)Delta[CaT], 212 +/- 4 microM ms-1). In contrast, the half-duration of (d/dt)Delta[CaT] was very similar in the two fibre types (slow-twitch, 1.8 +/- 0.1 ms; fast-twitch, 1.6 +/- 0.0 ms). When fibres were stimulated with a 5-shock train at 67 Hz, the peaks of (d/dt)Delta[CaT] in response to the second and subsequent shocks were much smaller than that due to the first shock; the later peaks, expressed as a fraction of the amplitude of the first peak, were similar in the two fibre types (slow-twitch, 0.2-0.3; fast-twitch, 0.1-0.3). The results support the conclusion that individual SR Ca2+ release units function similarly in slow-twitch and fast-twitch mammalian fibres.

  5. Properties of Ca2+ release induced by clofibric acid from the sarcoplasmic reticulum of mouse skeletal muscle fibres

    Science.gov (United States)

    Ikemoto, Takaaki; Endo, Makoto

    2001-01-01

    To characterize the effect of clofibric acid (Clof) on the Ca2+ release mechanism in the sarcoplasmic reticulum (SR) of skeletal muscle, we analysed the properties of Clof-induced Ca2+ release under various conditions using chemically skinned skeletal muscle fibres of the mouse.Clof (>0.5 mM) released Ca2+ from the SR under Ca2+-free conditions buffered with 10 mM EGTA (pCa >8).Co-application of ryanodine and Clof at pCa >8 but not ryanodine alone reduced the Ca2+ uptake capacity of the SR. Thus, Ca2+ release induced by Clof at pCa >8 must be a result of the activation of the ryanodine receptor (RyR).At pCa >8, (i) Clof-induced Ca2+ release was inhibited by adenosine monophosphate (AMP), (ii) the inhibitory effect of Mg2+ on the Clof-induced Ca2+ release was saturated at about 1 mM, and (iii) Clof-induced Ca2+ release was not inhibited by procaine (10 mM). These results indicate that Clof may activate the RyR-Ca2+ release channels in a manner different from Ca2+-induced Ca2+ release (CICR).In addition to this unique mode of opening, Clof also enhanced the CICR mode of opening of RyR-Ca2+ release channels.Apart from CICR, a high concentration of Ca2+ might also enhance the unique mode of opening by Clof.These results suggest that some features of Ca2+ release activated by Clof are similar to those of physiological Ca2+ release (PCR) in living muscle cells and raise the possibility that Clof may be useful in elucidating the mechanism of PCR in skeletal muscle. PMID:11606311

  6. Role of sarcoplasmic reticulum calcium in development of secondary calcium rise and early afterdepolarizations in long QT syndrome rabbit model.

    Directory of Open Access Journals (Sweden)

    Po-Cheng Chang

    Full Text Available L-type calcium current reactivation plays an important role in development of early afterdepolarizations (EADs and torsades de pointes (TdP. Secondary intracellular calcium (Cai rise is associated with initiation of EADs.To test whether inhibition of sarcoplasmic reticulum (SR Ca2+ cycling suppresses secondary Cai rise and genesis of EADs.Langendorff perfusion and dual voltage and Cai optical mapping were conducted in 10 rabbit hearts. Atrioventricular block (AVB was created by radiofrequency ablation. After baseline studies, E4031, SR Ca2+ cycling inhibitors (ryanodine plus thapsigargin and nifedipine were then administrated subsequently, and the protocols were repeated.At baseline, there was no spontaneous or pacing-induced TdP. After E4031 administration, action potential duration (APD was significantly prolonged and the amplitude of secondary Cai rise was enhanced, and 7 (70% rabbits developed spontaneous or pacing-induced TdP. In the presence of ryanodine plus thapsigargin, TdP inducibility was significantly reduced (2 hearts, 20%, p = 0.03. Although APD was significantly prolonged (from 298 ± 30 ms to 457 ± 75 ms at pacing cycle length of 1000 m, p = 0.007 by ryanodine plus thapsigargin, the secondary Cai rise was suppressed (from 8.8 ± 2.6% to 1.2 ± 0.9%, p = 0.02. Nifedipine inhibited TdP inducibility in all rabbit hearts.In this AVB and long QT rabbit model, inhibition of SR Ca2+ cycyling reduces the inducibility of TdP. The mechanism might be suppression of secondary Cai rise and genesis of EADs.

  7. Determination of the separate lipid and protein profile structures derived from the total membrane profile structure or isolated sarcoplasmic reticulum via x-ray and neutron diffraction

    International Nuclear Information System (INIS)

    Herbette, L.; Blasie, J.K.

    1984-01-01

    Sarcoplasmic reticulum (SR) membranes were prepared to contain biosynthetically deuterated SR phospholipids utilizing specific and general phospholipid exchange proteins (PLEP). Functional measurements and freeze fracture on SR dispersions and x-ray diffraction of hydrated oriented membrane multilayers revealed that the exchanged SR membranes were very similar to unexchanged SR membranes. Low resolution (28-A) neutron diffraction studies utilizing SR membranes exchanged with either protonated or perdeuterated SR phospholipids allowed direct determination of the lipid profile within the isolated SR membrane at two different unit cell repeat distances. These lipid profile structures were found to be highly asymmetric regarding the conformation of the fatty acid chain extents and compositional distribution of phospholipid molecules in the inner vs. outer monolayer of the SR membrane bilayer. The relatively high resolution (11-A) electron-density profile from x-ray diffraction was decomposed by utilizing the asymmetry in the number of phospholipid molecules residing in the inner vs. outer monolayer of the SR lipid bilayer as obtained from the neutron diffraction study. To our knowledge, this represents the first direct determination of a lipid bilayer profile structure within an isolated membrane system

  8. Interaction between neuronal nitric oxide synthase signaling and temperature influences sarcoplasmic reticulum calcium leak: role of nitroso-redox balance.

    Science.gov (United States)

    Dulce, Raul A; Mayo, Vera; Rangel, Erika B; Balkan, Wayne; Hare, Joshua M

    2015-01-02

    Although nitric oxide (NO) signaling modulates cardiac function and excitation-contraction coupling, opposing results because of inconsistent experimental conditions, particularly with respect to temperature, confound the ability to elucidate NO signaling pathways. Here, we show that temperature significantly modulates NO effects. To test the hypothesis that temperature profoundly affects nitroso-redox equilibrium, thereby affecting sarcoplasmic reticulum (SR) calcium (Ca(2+)) leak. We measured SR Ca(2+) leak in cardiomyocytes from wild-type (WT), NO/redox imbalance (neuronal nitric oxide synthase-deficient mice-1 [NOS1(-/-)]), and hyper S-nitrosoglutathione reductase-deficient (GSNOR(-/-)) mice. In WT cardiomyocytes, SR Ca(2+) leak increased because temperature decreased from 37°C to 23°C, whereas in NOS1(-/-) cells, the leak suddenly increased when the temperature surpassed 30°C. GSNOR(-/-) cardiomyocytes exhibited low leak throughout the temperature range. Exogenously added NO had a biphasic effect on NOS1(-/-) cardiomyocytes; reducing leak at 37°C but increasing it at subphysiological temperatures. Oxypurinol and Tempol diminished the leak in NOS1(-/-) cardiomyocytes. Cooling from 37°C to 23°C increased reactive oxygen species generation in WT but decreased it in NOS1(-/-) cardiomyocytes. Oxypurinol further reduced reactive oxygen species generation. At 23°C in WT cells, leak was decreased by tetrahydrobiopterin, an essential NOS cofactor. Cooling significantly increased SR Ca(2+) content in NOS1(-/-) cells but had no effect in WT or GSNOR(-/-). Ca(2+) leak and temperature are normally inversely proportional, whereas NOS1 deficiency reverses this effect, increasing leak and elevating reactive oxygen species production because temperature increases. Reduced denitrosylation (GSNOR deficiency) eliminates the temperature dependence of leak. Thus, temperature regulates the balance between NO and reactive oxygen species which in turn has a major effect on SR

  9. Effect of phospholipid, detergent and protein-protein interaction on stability and phosphoenzyme isomerization of soluble sarcoplasmic reticulum Ca-ATPase.

    Science.gov (United States)

    Vilsen, B; Andersen, J P

    1987-12-30

    The purpose of the present study was to elucidate the separate roles of lipid, detergent and protein-protein interaction for stability and catalytic properties of sarcoplasmic reticulum Ca-ATPase solubilized in the non-ionic detergent octa(ethylene glycol) monododecyl ether (C12E8). The use of large-zone high-performance liquid chromatography permitted us to define the self-association state of Ca-ATPase peptide at various detergent, phospholipid and protein concentrations, and also during enzymatic turnover with ATP. Conditions were established for monomerization of Ca-ATPase in the presence of a high concentration of phospholipid relative to detergent. The lipid-saturated monomeric preparation was relatively resistant to inactivation in the absence of Ca2+, whereas delipidated enzyme in monomeric or in oligomeric form was prone to inactivation. Kinetics of phosphoenzyme turnover were examined in the presence and absence of Mg2+. Dephosphorylation rates were sensitive to Mg2+, irrespective of whether the peptide was present in soluble monomeric form or was membrane-bound. C12E8-solubilized monomer without added phospholipid was, however, characterized by a fast initial phase of dephosphorylation in the absence of Mg2+. This was not observed with monomer saturated with phospholipid or with monomer solubilized in myristoylglycerophosphocholine or deoxycholate. The mechanism underlying this difference was shown to be a C12E8-induced acceleration of conversion of ADP-sensitive phosphoenzyme (E1P) to ADP-insensitive phosphoenzyme (E2P). The phosphoenzyme isomerization rate was also found to be enhanced by low-affinity binding of ATP. This was demonstrated both in membrane-bound and in soluble monomeric Ca-ATPase. Our results indicate that a single peptide chain constitutes the target for modulation of phosphoenzyme turnover by Mg2+ and ATP, and that detergent effects, distinct from those arising from disruption of protein-protein contacts, are the major determinants of

  10. Impact of sarcoplasmic reticulum calcium release on calcium dynamics and action potential morphology in human atrial myocytes: a computational study.

    Directory of Open Access Journals (Sweden)

    Jussi T Koivumäki

    Full Text Available Electrophysiological studies of the human heart face the fundamental challenge that experimental data can be acquired only from patients with underlying heart disease. Regarding human atria, there exist sizable gaps in the understanding of the functional role of cellular Ca²+ dynamics, which differ crucially from that of ventricular cells, in the modulation of excitation-contraction coupling. Accordingly, the objective of this study was to develop a mathematical model of the human atrial myocyte that, in addition to the sarcolemmal (SL ion currents, accounts for the heterogeneity of intracellular Ca²+ dynamics emerging from a structurally detailed sarcoplasmic reticulum (SR. Based on the simulation results, our model convincingly reproduces the principal characteristics of Ca²+ dynamics: 1 the biphasic increment during the upstroke of the Ca²+ transient resulting from the delay between the peripheral and central SR Ca²+ release, and 2 the relative contribution of SL Ca²+ current and SR Ca²+ release to the Ca²+ transient. In line with experimental findings, the model also replicates the strong impact of intracellular Ca²+ dynamics on the shape of the action potential. The simulation results suggest that the peripheral SR Ca²+ release sites define the interface between Ca²+ and AP, whereas the central release sites are important for the fire-diffuse-fire propagation of Ca²+ diffusion. Furthermore, our analysis predicts that the modulation of the action potential duration due to increasing heart rate is largely mediated by changes in the intracellular Na+ concentration. Finally, the results indicate that the SR Ca²+ release is a strong modulator of AP duration and, consequently, myocyte refractoriness/excitability. We conclude that the developed model is robust and reproduces many fundamental aspects of the tight coupling between SL ion currents and intracellular Ca²+ signaling. Thus, the model provides a useful framework for future

  11. Influence of the sarcoplasmic reticulum on the inotropic responses of the rat myocardium resulting from changes in rate and rhythm.

    Science.gov (United States)

    Mill, J G; Vassallo, D V; Leite, C M; Campagnaro, P

    1994-06-01

    1. The role of the sarcoplasmic reticulum (SR) in the inotropic responses produced by changes in stimulation rate and rhythm and resting tension was investigated in the rat myocardium. 2. Rat papillary muscles contracting isometrically (basic stimulation rate = 30/min) were superfused in vitro with normal Krebs solution and after addition of ryanodine (1 microM). Post-rest potentiation was obtained after pauses of 5, 10, 15, 30, 60 and 120 s, and the stimulation rate was changed from 6 to 90 bpm. Post-extrasystolic potentiation was induced by interpolating an extra stimulus after an interval of 413 +/- 15 ms. NiCl2 (2 mM) was used to confirm that contractions obtained after SR blockade with ryanodine were activated only by sarcolemmal calcium influx. 3. In the presence of ryanodine, the post-rest potentiation phenomenon disappears and the force-frequency relationship changes from the typical force decrease produced by rate increase to force increase. Under the effect of ryanodine, resting tension increased with the increase in stimulation rate. This behavior was enhanced by reducing extracellular KCl from 5.4 mM to 1 mM. This maneuver decreases Na(+)-K(+)-ATPase and increases intracellular Na+ activity, which reduces Ca2+ extrusion through the Na(+)-Ca2+ exchange mechanism. 4. SR participation in the post-extrasystolic potentiation phenomenon is also suggested because ryanodine treatment reversed the extrasystolic force depression into potentiation. In the presence of ryanodine, blockade of Ca2+ influx with NiCl2 (2 mM) abolished isometric contractions indicating that after SR blockade contractions are mainly dependent on sarcolemmal Ca2+ influx. 5. The results suggest that the SR is involved in the genesis of post-rest potentiation and contributes to the typical force-frequency relationship of the rat myocardium and to the post-extrasystolic potentiation phenomenon. Moreover, SR activity seems to be important for the maintenance of low resting tension in the

  12. Nitric oxide-dependent activation of CaMKII increases diastolic sarcoplasmic reticulum calcium release in cardiac myocytes in response to adrenergic stimulation.

    Science.gov (United States)

    Curran, Jerry; Tang, Lifei; Roof, Steve R; Velmurugan, Sathya; Millard, Ashley; Shonts, Stephen; Wang, Honglan; Santiago, Demetrio; Ahmad, Usama; Perryman, Matthew; Bers, Donald M; Mohler, Peter J; Ziolo, Mark T; Shannon, Thomas R

    2014-01-01

    Spontaneous calcium waves in cardiac myocytes are caused by diastolic sarcoplasmic reticulum release (SR Ca(2+) leak) through ryanodine receptors. Beta-adrenergic (β-AR) tone is known to increase this leak through the activation of Ca-calmodulin-dependent protein kinase (CaMKII) and the subsequent phosphorylation of the ryanodine receptor. When β-AR drive is chronic, as observed in heart failure, this CaMKII-dependent effect is exaggerated and becomes potentially arrhythmogenic. Recent evidence has indicated that CaMKII activation can be regulated by cellular oxidizing agents, such as reactive oxygen species. Here, we investigate how the cellular second messenger, nitric oxide, mediates CaMKII activity downstream of the adrenergic signaling cascade and promotes the generation of arrhythmogenic spontaneous Ca(2+) waves in intact cardiomyocytes. Both SCaWs and SR Ca(2+) leak were measured in intact rabbit and mouse ventricular myocytes loaded with the Ca-dependent fluorescent dye, fluo-4. CaMKII activity in vitro and immunoblotting for phosphorylated residues on CaMKII, nitric oxide synthase, and Akt were measured to confirm activity of these enzymes as part of the adrenergic cascade. We demonstrate that stimulation of the β-AR pathway by isoproterenol increased the CaMKII-dependent SR Ca(2+) leak. This increased leak was prevented by inhibition of nitric oxide synthase 1 but not nitric oxide synthase 3. In ventricular myocytes isolated from wild-type mice, isoproterenol stimulation also increased the CaMKII-dependent leak. Critically, in myocytes isolated from nitric oxide synthase 1 knock-out mice this effect is ablated. We show that isoproterenol stimulation leads to an increase in nitric oxide production, and nitric oxide alone is sufficient to activate CaMKII and increase SR Ca(2+) leak. Mechanistically, our data links Akt to nitric oxide synthase 1 activation downstream of β-AR stimulation. Collectively, this evidence supports the hypothesis that CaMKII is

  13. A novel artificial microRNA expressing AAV vector for phospholamban silencing in cardiomyocytes improves Ca2+ uptake into the sarcoplasmic reticulum.

    Directory of Open Access Journals (Sweden)

    Tobias Gröβl

    Full Text Available In failing rat hearts, post-transcriptonal inhibition of phospholamban (PLB expression by AAV9 vector-mediated cardiac delivery of short hairpin RNAs directed against PLB (shPLBr improves both impaired SERCA2a controlled Ca2+ cycling and contractile dysfunction. Cardiac delivery of shPLB, however, was reported to cause cardiac toxicity in canines. Thus we developed a new AAV vector, scAAV6-amiR155-PLBr, expressing a novel engineered artificial microRNA (amiR155-PLBr directed against PLB under control of a heart-specific hybrid promoter. Its PLB silencing efficiency and safety were compared with those of an AAV vector expressing shPLBr (scAAV6-shPLBr from an ubiquitously active U6 promoter. Investigations were carried out in cultured neonatal rat cardiomyocytes (CM over a period of 14 days. Compared to shPLBr, amiR155-PLBr was expressed at a significantly lower level, resulting in delayed and less pronounced PLB silencing. Despite decreased knockdown efficiency of scAAV6-amiR155-PLBr, a similar increase of the SERCA2a-catalyzed Ca2+ uptake into sarcoplasmic reticulum (SR vesicles was observed for both the shPLBr and amiR155-PLBr vectors. Proteomic analysis confirmed PLB silencing of both therapeutic vectors and revealed that shPLBr, but not the amiR155-PLBr vector, increased the proinflammatory proteins STAT3, STAT1 and activated STAT1 phosphorylation at the key amino acid residue Tyr701. Quantitative RT-PCR analysis detected alterations in the expression of several cardiac microRNAs after treatment of CM with scAAV6-shPLBr and scAAV6-amiR155-PLBr, as well as after treatment with its related amiR155- and shRNAs-expressing control AAV vectors. The results demonstrate that scAAV6-amiR155-PLBr is capable of enhancing the Ca2+ transport function of the cardiac SR PLB/SERCA2a system as efficiently as scAAV6-shPLBr while offering a superior safety profile.

  14. Calsequestrin content and SERCA determine normal and maximal Ca2+ storage levels in sarcoplasmic reticulum of fast- and slow-twitch fibres of rat.

    Science.gov (United States)

    Murphy, Robyn M; Larkins, Noni T; Mollica, Janelle P; Beard, Nicole A; Lamb, Graham D

    2009-01-15

    Whilst calsequestrin (CSQ) is widely recognized as the primary Ca2+ buffer in the sarcoplasmic reticulum (SR) in skeletal muscle fibres, its total buffering capacity and importance have come into question. This study quantified the absolute amount of CSQ isoform 1 (CSQ1, the primary isoform) present in rat extensor digitorum longus (EDL) and soleus fibres, and related this to their endogenous and maximal SR Ca2+ content. Using Western blotting, the entire constituents of minute samples of muscle homogenates or segments of individual muscle fibres were compared with known amounts of purified CSQ1. The fidelity of the analysis was proven by examining the relative signal intensity when mixing muscle samples and purified CSQ1. The CSQ1 contents of EDL fibres, almost exclusively type II fibres, and soleus type I fibres [SOL (I)] were, respectively, 36 +/- 2 and 10 +/- 1 micromol (l fibre volume)(-1), quantitatively accounting for the maximal SR Ca2+ content of each. Soleus type II [SOL (II)] fibres (approximately 20% of soleus fibres) had an intermediate amount of CSQ1. Every SOL (I) fibre examined also contained some CSQ isoform 2 (CSQ2), which was absent in every EDL and other type II fibre except for trace amounts in one case. Every EDL and other type II fibre had a high density of SERCA1, the fast-twitch muscle sarco(endo)plasmic reticulum Ca2+-ATPase isoform, whereas there was virtually no SERCA1 in any SOL (I) fibre. Maximal SR Ca2+ content measured in skinned fibres increased with CSQ1 content, and the ratio of endogenous to maximal Ca2+ content was inversely correlated with CSQ1 content. The relative SR Ca2+ content that could be maintained in resting cytoplasmic conditions was found to be much lower in EDL fibres than in SOL (I) fibres (approximately 20 versus >60%). Leakage of Ca2+ from the SR in EDL fibres could be substantially reduced with a SR Ca2+ pump blocker and increased by adding creatine to buffer cytoplasmic [ADP] at a higher level, both results

  15. 3-Bromopyruvate inhibits calcium uptake by sarcoplasmic reticulum vesicles but not SERCA ATP hydrolysis activity.

    Science.gov (United States)

    Jardim-Messeder, Douglas; Camacho-Pereira, Juliana; Galina, Antonio

    2012-05-01

    3-Bromopyruvate (3BrPA) is an antitumor agent that alkylates the thiol groups of enzymes and has been proposed as a treatment for neoplasias because of its specific reactivity with metabolic energy transducing enzymes in tumor cells. In this study, we show that the sarco/endoplasmic reticulum calcium (Ca(2+)) ATPase (SERCA) type 1 is one of the target enzymes of 3BrPA activity. Sarco/endoplasmic reticulum vesicles (SRV) were incubated in the presence of 1mM 3BrPA, which was unable to inhibit the ATPase activity of SERCA. However, Ca(2+)-uptake activity was significantly inhibited by 80% with 150 μM 3BrPA. These results indicate that 3BrPA has the ability to uncouple the ATP hydrolysis from the calcium transport activities. In addition, we observed that the inclusion of 2mM reduced glutathione (GSH) in the reaction medium with different 3BrPA concentrations promoted an increase in 40% in ATPase activity and protects the inhibition promoted by 3BrPA in calcium uptake activity. This derivatization is accompanied by a decrease of reduced cysteine (Cys), suggesting that GSH and 3BrPA increases SERCA activity and transport by pyruvylation and/or S-glutathiolation mediated by GSH at a critical Cys residues of the SERCA. Copyright © 2012 Elsevier Ltd. All rights reserved.

  16. The sarcolipin-bound calcium pump stabilizes calcium sites exposed to the cytoplasm

    DEFF Research Database (Denmark)

    Winther, Anne-Marie Lund; Bublitz, Maike; Karlsen, Jesper Lykkegaard

    2013-01-01

    The contraction and relaxation of muscle cells is controlled by the successive rise and fall of cytosolic Ca(2+), initiated by the release of Ca(2+) from the sarcoplasmic reticulum and terminated by re-sequestration of Ca(2+) into the sarcoplasmic reticulum as the main mechanism of Ca(2+) removal...

  17. Cannabinoid signalling inhibits sarcoplasmic Ca2+ release and regulates excitation–contraction coupling in mammalian skeletal muscle

    Science.gov (United States)

    Oláh, Tamás; Bodnár, Dóra; Tóth, Adrienn; Vincze, János; Fodor, János; Reischl, Barbara; Kovács, Adrienn; Ruzsnavszky, Olga; Dienes, Beatrix; Szentesi, Péter; Friedrich, Oliver

    2016-01-01

    Key points Marijuana was found to cause muscle weakness, although the exact regulatory role of its receptors (CB1 cannabinoid receptor; CB1R) in the excitation–contraction coupling (ECC) of mammalian skeletal muscle remains unknown.We found that CB1R activation or its knockout did not affect muscle force directly, whereas its activation decreased the Ca2+‐sensitivity of the contractile apparatus and made the muscle fibres more prone to fatigue.We demonstrate that CB1Rs are not connected to the inositol 1,4,5‐trisphosphate pathway either in myotubes or in adult muscle fibres.By contrast, CB1Rs constitutively inhibit sarcoplasmic Ca2+ release and sarcoplasmic reticulum Ca2+ ATPase during ECC in a Gi/o protein‐mediated way in adult skeletal muscle fibres but not in myotubes.These results help with our understanding of the physiological effects and pathological consequences of CB1R activation in skeletal muscle and may be useful in the development of new cannabinoid drugs. Abstract Marijuana was found to cause muscle weakness, although it is unknown whether it affects the muscles directly or modulates only the motor control of the central nervous system. Although the presence of CB1 cannabinoid receptors (CB1R), which are responsible for the psychoactive effects of the drug in the brain, have recently been demonstrated in skeletal muscle, it is unclear how CB1R‐mediated signalling affects the contraction and Ca²⁺ homeostasis of mammalian skeletal muscle. In the present study, we demonstrate that in vitro CB1R activation increased muscle fatigability and decreased the Ca2+‐sensitivity of the contractile apparatus, whereas it did not alter the amplitude of single twitch contractions. In myotubes, CB1R agonists neither evoked, nor influenced inositol 1,4,5‐trisphosphate (IP3)‐mediated Ca2+ transients, nor did they alter excitation–contraction coupling. By contrast, in isolated muscle fibres of wild‐type mice, although CB1R agonists did not evoke IP3

  18. Cannabinoid signalling inhibits sarcoplasmic Ca2+ release and regulates excitation-contraction coupling in mammalian skeletal muscle.

    Science.gov (United States)

    Oláh, Tamás; Bodnár, Dóra; Tóth, Adrienn; Vincze, János; Fodor, János; Reischl, Barbara; Kovács, Adrienn; Ruzsnavszky, Olga; Dienes, Beatrix; Szentesi, Péter; Friedrich, Oliver; Csernoch, László

    2016-12-15

    Marijuana was found to cause muscle weakness, although the exact regulatory role of its receptors (CB1 cannabinoid receptor; CB1R) in the excitation-contraction coupling (ECC) of mammalian skeletal muscle remains unknown. We found that CB1R activation or its knockout did not affect muscle force directly, whereas its activation decreased the Ca 2+ -sensitivity of the contractile apparatus and made the muscle fibres more prone to fatigue. We demonstrate that CB1Rs are not connected to the inositol 1,4,5-trisphosphate pathway either in myotubes or in adult muscle fibres. By contrast, CB1Rs constitutively inhibit sarcoplasmic Ca 2+ release and sarcoplasmic reticulum Ca 2+ ATPase during ECC in a G i/o protein-mediated way in adult skeletal muscle fibres but not in myotubes. These results help with our understanding of the physiological effects and pathological consequences of CB1R activation in skeletal muscle and may be useful in the development of new cannabinoid drugs. Marijuana was found to cause muscle weakness, although it is unknown whether it affects the muscles directly or modulates only the motor control of the central nervous system. Although the presence of CB1 cannabinoid receptors (CB1R), which are responsible for the psychoactive effects of the drug in the brain, have recently been demonstrated in skeletal muscle, it is unclear how CB1R-mediated signalling affects the contraction and Ca²⁺ homeostasis of mammalian skeletal muscle. In the present study, we demonstrate that in vitro CB1R activation increased muscle fatigability and decreased the Ca 2+ -sensitivity of the contractile apparatus, whereas it did not alter the amplitude of single twitch contractions. In myotubes, CB1R agonists neither evoked, nor influenced inositol 1,4,5-trisphosphate (IP 3 )-mediated Ca 2+ transients, nor did they alter excitation-contraction coupling. By contrast, in isolated muscle fibres of wild-type mice, although CB1R agonists did not evoke IP 3 -mediated Ca 2

  19. Muscle Glycogen Content Modifies SR Ca2 + Release Rate in Elite Endurance Athletes

    DEFF Research Database (Denmark)

    Gejl, Kasper Degn; Hvid, Lars G; Frandsen, Ulrik

    2014-01-01

    The aim of the present study was to investigate the influence of muscle glycogen content on sarcoplasmic reticulum (SR) function and peak power output (Wpeak) in elite endurance athletes.......The aim of the present study was to investigate the influence of muscle glycogen content on sarcoplasmic reticulum (SR) function and peak power output (Wpeak) in elite endurance athletes....

  20. Calsequestrin 2 deletion causes sinoatrial node dysfunction and atrial arrhythmias associated with altered sarcoplasmic reticulum calcium cycling and degenerative fibrosis within the mouse atrial pacemaker complex1

    Science.gov (United States)

    Glukhov, Alexey V.; Kalyanasundaram, Anuradha; Lou, Qing; Hage, Lori T.; Hansen, Brian J.; Belevych, Andriy E.; Mohler, Peter J.; Knollmann, Björn C.; Periasamy, Muthu; Györke, Sandor; Fedorov, Vadim V.

    2015-01-01

    Aims Loss-of-function mutations in Calsequestrin 2 (CASQ2) are associated with catecholaminergic polymorphic ventricular tachycardia (CPVT). CPVT patients also exhibit bradycardia and atrial arrhythmias for which the underlying mechanism remains unknown. We aimed to study the sinoatrial node (SAN) dysfunction due to loss of CASQ2. Methods and results In vivo electrocardiogram (ECG) monitoring, in vitro high-resolution optical mapping, confocal imaging of intracellular Ca2+ cycling, and 3D atrial immunohistology were performed in wild-type (WT) and Casq2 null (Casq2−/−) mice. Casq2−/− mice exhibited bradycardia, SAN conduction abnormalities, and beat-to-beat heart rate variability due to enhanced atrial ectopic activity both at baseline and with autonomic stimulation. Loss of CASQ2 increased fibrosis within the pacemaker complex, depressed primary SAN activity, and conduction, but enhanced atrial ectopic activity and atrial fibrillation (AF) associated with macro- and micro-reentry during autonomic stimulation. In SAN myocytes, CASQ2 deficiency induced perturbations in intracellular Ca2+ cycling, including abnormal Ca2+ release, periods of significantly elevated diastolic Ca2+ levels leading to pauses and unstable pacemaker rate. Importantly, Ca2+ cycling dysfunction occurred not only at the SAN cellular level but was also globally manifested as an increased delay between action potential (AP) and Ca2+ transient upstrokes throughout the atrial pacemaker complex. Conclusions Loss of CASQ2 causes abnormal sarcoplasmic reticulum Ca2+ release and selective interstitial fibrosis in the atrial pacemaker complex, which disrupt SAN pacemaking but enhance latent pacemaker activity, create conduction abnormalities and increase susceptibility to AF. These functional and extensive structural alterations could contribute to SAN dysfunction as well as AF in CPVT patients. PMID:24216388

  1. Temperature dependence of the kinetics of isometric myocardium relaxation

    Energy Technology Data Exchange (ETDEWEB)

    Izakov, V.Ya.; Bykov, B.L.; Kimmelman, I.Ya.

    1981-11-01

    The dependence of the exponential decay constant expressing the isometric relaxation of the myocardium on temperature is investigated in animals with various specific contents of myocardial sarcoplasmic reticulum. Experiments were performed on cardiac ventricles and atria isolated from rabbits, frogs and turtles and electrically stimulated to produce maximal contraction at temperatures from 10 to 35 C. Arrhenius plots derived from the data are found to be linear in the myocardia of the rabbit and frog, with a greater activation energy for the relaxation found in the rabbit. The Arrhenius plot for the turtle, which has a sarcoplasmic reticulum content intermediate between those of the frog and rabbit, corresponds to two straight lines with different activation energies. Results thus support the hypothesis of two separate mechanisms of calcium removal, involving the sarcoplasmic reticulum and cellular membrane, in muscle relaxation.

  2. Nanospan, an alternatively spliced isoform of sarcospan, localizes to the sarcoplasmic reticulum in skeletal muscle and is absent in limb girdle muscular dystrophy 2F.

    Science.gov (United States)

    Peter, Angela K; Miller, Gaynor; Capote, Joana; DiFranco, Marino; Solares-Pérez, Alhondra; Wang, Emily L; Heighway, Jim; Coral-Vázquez, Ramón M; Vergara, Julio; Crosbie-Watson, Rachelle H

    2017-06-06

    Sarcospan (SSPN) is a transmembrane protein that interacts with the sarcoglycans (SGs) to form a tight subcomplex within the dystrophin-glycoprotein complex that spans the sarcolemma and interacts with laminin in the extracellular matrix. Overexpression of SSPN ameliorates Duchenne muscular dystrophy in murine models. Standard cloning approaches were used to identify nanospan, and nanospan-specific polyclonal antibodies were generated and validated. Biochemical isolation of skeletal muscle membranes and two-photon laser scanning microscopy were used to analyze nanospan localization in muscle from multiple murine models. Duchenne muscular dystrophy biopsies were analyzed by immunoblot analysis of protein lysates as well as indirect immunofluorescence analysis of muscle cryosections. Nanospan is an alternatively spliced isoform of sarcospan. While SSPN has four transmembrane domains and is a core component of the sarcolemmal dystrophin-glycoprotein complex, nanospan is a type II transmembrane protein that does not associate with the dystrophin-glycoprotein complex. We demonstrate that nanospan is enriched in the sarcoplasmic reticulum (SR) fractions and is not present in the T-tubules. SR fractions contain membranes from three distinct structural regions: a region flanking the T-tubules (triadic SR), a SR region across the Z-line (ZSR), and a longitudinal SR region across the M-line (LSR). Analysis of isolated murine muscles reveals that nanospan is mostly associated with the ZSR and triadic SR, and only minimally with the LSR. Furthermore, nanospan is absent from the SR of δ-SG-null (Sgcd -/- ) skeletal muscle, a murine model for limb girdle muscular dystrophy 2F. Analysis of skeletal muscle biopsies from Duchenne muscular dystrophy patients reveals that nanospan is preferentially expressed in type I (slow) fibers in both control and Duchenne samples. Furthermore, nanospan is significantly reduced in Duchenne biopsies. Alternative splicing of proteins from the SG

  3. Picture frame fibres in a carrier of the trait for malignant hyperpyrexia

    Energy Technology Data Exchange (ETDEWEB)

    Isaacs, H; Badenhorst, M [University of the Witwatersrand, Johannesburg (South Africa). Department of Physiology; Heffron, J J.A. [University of the Witwatersrand, Johannesburg (South Africa). Department of Physiological Chemistry

    1975-11-01

    A member of a family which was known to be susceptible to malignant hyperpyrexia, who was identified as a carrier by the presence of an elevated serum creatinephosphokinase, has been investigated further. Muscle was examined biochemically, and the study included the sarcoplasmic ATPase-activity, actinomycin, Mg2+ ATPase activity, ATP, phosphocreatine and glucose-6-phosphate. In addition, the calcium uptake by the sarcoplasmic reticulum was studied. The histochemical analysis of the muscle revealed the presence of a new fibre type characterized by a dense rim of ATPase activity, which gives the impression of a 'picture-frame'. Ultramicroscopic study revealed changes in the mitochondria and areas of myofibrillar disruption with swelling of the sarcoplasmic reticulum.

  4. Picture frame fibres in a carrier of the trait for malignant hyperpyrexia

    International Nuclear Information System (INIS)

    Isaacs, H.; Badenhorst, M.; Heffron, J.J.A.

    1975-01-01

    A member of a family which was known to be susceptible to malignant hyperpyrexia, who was identified as a carrier by the presence of an elevated serum creatinephosphokinase, has been investigated further. Muscle was examined biochemically, and the study included the sarcoplasmic ATPase-activity, actinomycin, Mg2+ ATPase activity, ATP, phosphocreatine and glucose-6-phosphate. In addition, the calcium uptake by the sarcoplasmic reticulum was studied. The histochemical analysis of the muscle revealed the presence of a new fibre type characterized by a dense rim of ATPase activity, which gives the impression of a 'picture-frame'. Ultramicroscopic study revealed changes in the mitochondria and areas of myofibrillar disruption with swelling of the sarcoplasmic reticulum

  5. A low-dose β1-blocker in combination with milrinone improves intracellular Ca2+ handling in failing cardiomyocytes by inhibition of milrinone-induced diastolic Ca2+ leakage from the sarcoplasmic reticulum.

    Directory of Open Access Journals (Sweden)

    Shigeki Kobayashi

    Full Text Available OBJECTIVES: The purpose of this study was to investigate whether adding a low-dose β1-blocker to milrinone improves cardiac function in failing cardiomyocytes and the underlying cardioprotective mechanism. BACKGROUND: The molecular mechanism underlying how the combination of low-dose β1-blocker and milrinone affects intracellular Ca(2+ handling in heart failure remains unclear. METHODS: We investigated the effect of milrinone plus landiolol on intracellular Ca(2+ transient (CaT, cell shortening (CS, the frequency of diastolic Ca(2+ sparks (CaSF, and sarcoplasmic reticulum Ca(2+ concentration ({Ca(2+}SR in normal and failing canine cardiomyocytes and used immunoblotting to determine the phosphorylation level of ryanodine receptor (RyR2 and phospholamban (PLB. RESULTS: In failing cardiomyocytes, CaSF significantly increased, and peak CaT and CS markedly decreased compared with normal myocytes. Administration of milrinone alone slightly increased peak CaT and CS, while CaSF greatly increased with a slight increase in {Ca(2+}SR. Co-administration of β1-blocker landiolol to failing cardiomyocytes at a dose that does not inhibit cardiomyocyte function significantly decreased CaSF with a further increase in {Ca(2+}SR, and peak CaT and CS improved compared with milrinone alone. Landiolol suppressed the hyperphosphorylation of RyR2 (Ser2808 in failing cardiomyocytes but had no effect on levels of phosphorylated PLB (Ser16 and Thr17. Low-dose landiolol significantly inhibited the alternans of CaT and CS under a fixed pacing rate (0.5 Hz in failing cardiomyocytes. CONCLUSION: A low-dose β1-blocker in combination with milrinone improved cardiac function in failing cardiomyocytes, apparently by inhibiting the phosphorylation of RyR2, not PLB, and subsequent diastolic Ca(2+ leak.

  6. A low-dose β1-blocker in combination with milrinone improves intracellular Ca2+ handling in failing cardiomyocytes by inhibition of milrinone-induced diastolic Ca2+ leakage from the sarcoplasmic reticulum.

    Science.gov (United States)

    Kobayashi, Shigeki; Susa, Takehisa; Ishiguchi, Hironori; Myoren, Takeki; Murakami, Wakako; Kato, Takayoshi; Fukuda, Masakazu; Hino, Akihiro; Suetomi, Takeshi; Ono, Makoto; Uchinoumi, Hitoshi; Tateishi, Hiroki; Mochizuki, Mamoru; Oda, Tetsuro; Okuda, Shinichi; Doi, Masahiro; Yamamoto, Takeshi; Yano, Masafumi

    2015-01-01

    The purpose of this study was to investigate whether adding a low-dose β1-blocker to milrinone improves cardiac function in failing cardiomyocytes and the underlying cardioprotective mechanism. The molecular mechanism underlying how the combination of low-dose β1-blocker and milrinone affects intracellular Ca(2+) handling in heart failure remains unclear. We investigated the effect of milrinone plus landiolol on intracellular Ca(2+) transient (CaT), cell shortening (CS), the frequency of diastolic Ca(2+) sparks (CaSF), and sarcoplasmic reticulum Ca(2+) concentration ({Ca(2+)}SR) in normal and failing canine cardiomyocytes and used immunoblotting to determine the phosphorylation level of ryanodine receptor (RyR2) and phospholamban (PLB). In failing cardiomyocytes, CaSF significantly increased, and peak CaT and CS markedly decreased compared with normal myocytes. Administration of milrinone alone slightly increased peak CaT and CS, while CaSF greatly increased with a slight increase in {Ca(2+)}SR. Co-administration of β1-blocker landiolol to failing cardiomyocytes at a dose that does not inhibit cardiomyocyte function significantly decreased CaSF with a further increase in {Ca(2+)}SR, and peak CaT and CS improved compared with milrinone alone. Landiolol suppressed the hyperphosphorylation of RyR2 (Ser2808) in failing cardiomyocytes but had no effect on levels of phosphorylated PLB (Ser16 and Thr17). Low-dose landiolol significantly inhibited the alternans of CaT and CS under a fixed pacing rate (0.5 Hz) in failing cardiomyocytes. A low-dose β1-blocker in combination with milrinone improved cardiac function in failing cardiomyocytes, apparently by inhibiting the phosphorylation of RyR2, not PLB, and subsequent diastolic Ca(2+) leak.

  7. Time Course of the Response of Myofibrillar and Sarcoplasmic Protein Metabolism to Unweighting of the Soleus Muscle

    Science.gov (United States)

    Munoz, Kathryn A.; Satarug, Soisungwan; Tischler, Marc E.

    1993-01-01

    Contributions of altered in vivo protein synthesis and degradation to unweighting atrophy of the soleus muscle in tail-suspended young female rats were analyzed daily for up to 6 days. Specific changes in myofibrillar and sarcoplasmic proteins were also evaluated to assess their contributions to the loss of total protein. Synthesis of myofibrillar and sarcoplasmic proteins was estimated by intramuscular (IM) injection and total protein by intraperitoneal (IP) injection of flooding doses of H-3-phenylaianine. Total protein loss was greatest during the first 3 days following suspension and was a consequence of the loss of myofibrillar rather than sarcoplasmic proteins. However, synthesis of total myofibrillar and sarcoplasmic proteins diminished in parallel beginning in the first 24 hours. Therefore sarcoplasmic proteins must be spared due to a decrease in their degradation. In contrast, myofibrillar protein degradation increased, thus explaining the elevated degradation of the total pool. Following 72 hours of suspension, protein synthesis remained low, but the rate of myofibrillar protein loss diminished, suggesting a slowing of degradation. These various results show acute loss of protein during unweighting atrophy is a consequence of decreased synthesis and increased degradation of myofibrillar proteins, and sarcoplasmic proteins are spared due to slower degradation, likely explaining the sparing of plasma membrane receptors. Based on other published data, we propose that the slowing of atrophy after the initial response may be attributed to an increased effect of insulin.

  8. A model of propagating calcium-induced calcium release mediated by calcium diffusion

    NARCIS (Netherlands)

    Backx, P. H.; de Tombe, P. P.; van Deen, J. H.; Mulder, B. J.; ter Keurs, H. E.

    1989-01-01

    The effect of sudden local fluctuations of the free sarcoplasmic [Ca++]i in cardiac cells on calcium release and calcium uptake by the sarcoplasmic reticulum (SR) was calculated with the aid of a simplified model of SR calcium handling. The model was used to evaluate whether propagation of calcium

  9. Contractile properties and sarcoplasmic reticulum calcium content in type I and type II skeletal muscle fibres in active aged humans.

    Science.gov (United States)

    Lamboley, C R; Wyckelsma, V L; Dutka, T L; McKenna, M J; Murphy, R M; Lamb, G D

    2015-06-01

    Muscle weakness in old age is due in large part to an overall loss of skeletal muscle tissue, but it remains uncertain how much also stems from alterations in the properties of the individual muscle fibres. This study examined the contractile properties and amount of stored intracellular calcium in single muscle fibres of Old (70 ± 4 years) and Young (22 ± 3 years) adults. The maximum level of force production (per unit cross-sectional area) in fast twitch fibres in Old subjects was lower than in Young subjects, and the fibres were also less sensitive to activation by calcium. The amount of calcium stored inside muscle fibres and available to trigger contraction was also lower in both fast- and slow-twitch muscle fibres in the Old subjects. These findings indicate that muscle weakness in old age stems in part from an impaired capacity for force production in the individual muscle fibres. This study examined the contractile properties and sarcoplasmic reticulum (SR) Ca(2+) content in mechanically skinned vastus lateralis muscle fibres of Old (70 ± 4 years) and Young (22 ± 3 years) humans to investigate whether changes in muscle fibre properties contribute to muscle weakness in old age. In type II fibres of Old subjects, specific force was reduced by ∼17% and Ca(2+) sensitivity was also reduced (pCa50 decreased ∼0.05 pCa units) relative to that in Young. S-Glutathionylation of fast troponin I (TnIf ) markedly increased Ca(2+) sensitivity in type II fibres, but the increase was significantly smaller in Old versus Young (+0.136 and +0.164 pCa unit increases, respectively). Endogenous and maximal SR Ca(2+) content were significantly smaller in both type I and type II fibres in Old subjects. In fibres of Young, the SR could be nearly fully depleted of Ca(2+) by a combined caffeine and low Mg(2+) stimulus, whereas in fibres of Old the amount of non-releasable Ca(2+) was significantly increased (by > 12% of endogenous Ca(2+) content). Western

  10. Solution-blown nanofiber mats from fish sarcoplasmic protein

    DEFF Research Database (Denmark)

    Sett, S.; Boutrup Stephansen, Karen; Yarin, A.L.

    2016-01-01

    In the present work, solution-blowing was adopted to form nanofibers from fish sarcoplasmic proteins (FSPs). Nanofiber mats containing different weight ratios (up to 90/10) of FSP in the FSP/nylon 6 blended nanofibers were formed from formic acid solutions, and compared to electrospun fibers made...... that the production rate of solution-blowing was increased 30-fold in relation to electrospinning. Overall, this study reveals FSP as an interesting biopolymeric alternative to synthetic polymers, and the introduction of FSP to nylon 6 provides a composite with controlled properties....

  11. Comparative profiling of sarcoplasmic phosphoproteins in ovine muscle with different color stability.

    Science.gov (United States)

    Li, Meng; Li, Zheng; Li, Xin; Xin, Jianzeng; Wang, Ying; Li, Guixia; Wu, Liguo; Shen, Qingwu W; Zhang, Dequan

    2018-02-01

    The phosphorylation of sarcoplasmic proteins in postmortem muscles was investigated in relationship to color stability in the present study. Although no difference was observed in the global phosphorylation level of sarcoplasmic proteins, difference was determined in the phosphorylation levels of individual protein bands from muscles with different color stability. Correlation analysis and liquid chromatography - tandem mass spectrometry (LC-MS/MS) identification of phosphoproteins showed that most of the color stability-related proteins were glycolytic enzymes. Interestingly, the phosphorylation level of myoglobin was inversely related to meat color stability. As the phosphorylation of myoglobin increased, color stability based on a ∗ value decreased and metMb content increased. In summary, the study revealed that protein phosphorylation might play a role in the regulation of meat color stability probably by regulating glycolysis and the redox stability of myoglobin, which might be affected by the phosphorylation of myoglobin. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Source Segregation and Collection of Source-Segregated Waste

    DEFF Research Database (Denmark)

    Christensen, Thomas Højlund; Matsufuji, Y.

    2011-01-01

    of optimal handling of the waste. But in a few cases, the waste must also be separated at source, for example removing the protective plastic cover from a commercial advertisement received by mail, prior to putting the advertisement into the waste collection bin for recyclable paper. These issues are often...... in wastes segregation addressing: - Purpose of source segregation. - Segregation criteria and guidance. - Segregation potentials and efficiencies. - Systems for collecting segregated fraction....

  13. Is contraction-stimulated glucose transport feedforward regulated by Ca2+?

    DEFF Research Database (Denmark)

    Jensen, Thomas Elbenhardt; Angin, Yeliz; Sylow, Lykke

    2014-01-01

    cell types. The literature is contrasted against our recent findings suggesting that SR Ca(2+) release is neither essential nor adequate to stimulate glucose transport in muscle. Instead, feedback signals through AMPK and mechanical stress are likely to account for most of contraction......In many cell types, Ca(2+) signals to increase the movement and surface membrane insertion of vesicles. In skeletal muscle, Ca(2+) is predominantly released from the sarcoplasmic reticulum (SR) to initiate contraction. Sarcoplasmic reticulum Ca(2+) release is widely believed to be a direct......-stimulated glucose transport. A revised working model is proposed, in which muscle glucose transport during contraction is not directly regulated by SR Ca(2+) release but rather responds exclusively to feedback signals activated secondary to cross-bridge cycling and tension development....

  14. ALUMINUM CHLORIDE EFFECT ON Ca2+,Mg(2+)-ATPase ACTIVITY AND DYNAMIC PARAMETERS OF SKELETAL MUSCLE CONTRACTION.

    Science.gov (United States)

    Nozdrenko, D M; Abramchuk, O M; Soroca, V M; Miroshnichenko, N S

    2015-01-01

    We studied enzymatic activity and measured strain-gauge contraction properties of the frog Rana temporaria m. tibialis anterior muscle fascicles during the action of aluminum chloride solution. It was shown that AlCl3 solutions did not affect the dynamic properties of skeletal muscle preparation in concentrations less than 10(-4) M Increasing the concentration of AlCl3 to 10(-2) M induce complete inhibition of muscle contraction. A linear correlation between decrease in Ca2+,Mg(2+)-ATPase activity of sarcoplasmic reticulum and the investigated concentrations range of aluminum chloride was observed. The reduction in the dynamic contraction performance and the decrease Ca2+,Mg(2+)-ATPase activity of the sarcoplasmic reticulum under the effect of the investigated AlCl3 solution were minimal in pre-tetanus period of contraction.

  15. Aluminum chloride effect on Ca(2+,Mg(2+-ATPase activity and dynamic parameters of skeletal muscle contraction

    Directory of Open Access Journals (Sweden)

    D. M. Nozdrenko

    2015-10-01

    Full Text Available We studied enzymatic activity and measured strain-gauge contraction properties of the frog Rana temporaria m. tibialis anterior muscle fascicles during the action of aluminum chloride solution. It was shown that AlCl3 solutions did not affect the dynamic properties of skeletal muscle preparation in concentrations less than 10-4 M. Increasing the concentration of AlCl3 to 10-2 M induce complete inhibition of muscle contraction. A linear correlation between decrease in Ca2+,Mg2+-ATPase activity of sarcoplasmic reticulum and the investigated concentrations range of aluminum chloride was observed. The reduction in the dynamic contraction performance and the decrease Ca2+,Mg2+-ATPase activity of the sarcoplasmic reticulum under the effect of the investigated AlCl3 solution were minimal in pre-tetanus period of contraction.

  16. Subcellular distribution of glycogen and decreased tetanic Ca2+ in fatigued single intact mouse muscle fibres

    DEFF Research Database (Denmark)

    Nielsen, Joachim; Cheng, Arthur J; Ørtenblad, Niels

    2014-01-01

    In skeletal muscle fibres, glycogen has been shown to be stored at different subcellular locations: (i) between the myofibrils (intermyofibrillar); (ii) within the myofibrils (intramyofibrillar); and (iii) subsarcolemmal. Of these, intramyofibrillar glycogen has been implied as a critical regulator...... of sarcoplasmic reticulum Ca(2+) release. The aim of the present study was to test directly how the decrease in cytoplasmic free Ca(2+) ([Ca(2+)]i) during repeated tetanic contractions relates to the subcellular glycogen distribution. Single fibres of mouse flexor digitorum brevis muscles were fatigued with 70 Hz...... in tetanic [Ca(2+)]i, and hence force, is accompanied by major reductions in inter- and intramyofibrillar glycogen. The stronger correlation between decreased tetanic [Ca(2+)]i and reduced intramyofibrillar glycogen implies that sarcoplasmic reticulum Ca(2+) release critically depends on energy supply from...

  17. SR calcium handling and calcium after-transients in a rabbit model of heart failure

    NARCIS (Netherlands)

    Baartscheer, Antonius; Schumacher, Cees A.; Belterman, Charly N. W.; Coronel, Ruben; Fiolet, Jan W. T.

    2003-01-01

    Objective: After-depolarization associated arrhythmias are frequently observed in heart failure and associated with spontaneous calcium release from sarcoplasmic reticulum (SR), calcium after-transients. We hypothesize that disturbed SR calcium handling underlies calcium after-transients in heart

  18. Polarity and reorganization of the endoplasmic reticulum during fertilization and ooplasmic segregation in the ascidian egg

    OpenAIRE

    1993-01-01

    During the first cell cycle of the ascidian egg, two phases of ooplasmic segregation create distinct cytoplasmic domains that are crucial for later development. We recently defined a domain enriched in ER in the vegetal region of Phallusia mammillata eggs. To explore the possible physiological and developmental function of this ER domain, we here investigate its organization and fate by labeling the ER network in vivo with DiIC16(3), and observing its distribution before and after fertilizati...

  19. Intracellular calcium leak due to FKBP12.6 deficiency in mice facilitates the inducibility of atrial fibrillation

    NARCIS (Netherlands)

    Sood, Subeena; Chelu, Mihail G.; van Oort, Ralph J.; Skapura, Darlene; Santonastasi, Marco; Dobrev, Dobromir; Wehrens, Xander H. T.

    2008-01-01

    BACKGROUND: Although defective Ca(2+) homeostasis may contribute to arrhythmogenesis in atrial fibrillation (AF), the underlying molecular mechanisms remain poorly understood. Studies in patients with AF revealed that impaired diastolic closure of sarcoplasmic reticulum (SR) Ca(2+)-release channels

  20. Genetics Home Reference: Brody myopathy

    Science.gov (United States)

    ... 1 (SERCA1). The SERCA1 enzyme is found in skeletal muscle cells, specifically in the membrane of a structure called the sarcoplasmic reticulum . This structure plays a major role in muscle contraction and relaxation by storing and releasing positively charged ...

  1. Waste segregation

    International Nuclear Information System (INIS)

    Clark, D.E.; Colombo, P.

    1982-01-01

    A scoping study has been undertaken to determine the state-of-the-art of waste segregation technology as applied to the management of low-level waste (LLW). Present-day waste segregation practices were surveyed through a review of the recent literature and by means of personal interviews with personnel at selected facilities. Among the nuclear establishments surveyed were Department of Energy (DOE) laboratories and plants, nuclear fuel cycle plants, public and private laboratories, institutions, industrial plants, and DOE and commercially operated shallow land burial sites. These survey data were used to analyze the relationship between waste segregation practices and waste treatment/disposal processes, to assess the developmental needs for improved segregation technology, and to evaluate the costs and benefits associated with the implementation of waste segregation controls. This task was planned for completion in FY 1981. It should be noted that LLW management practices are now undergoing rapid change such that the technology and requirements for waste segregation in the near future may differ significantly from those of the present day. 8 figures

  2. [Changes induced by hypertonic solutions in the transportation of calcium by the cardiac reticular sarcoplasma].

    Science.gov (United States)

    Sierra, M; Holguín, J A

    1979-01-01

    In the sarcoplasmic reticulum of the myocardium, celular organell which function is to regulate the cytoplasmic concentration of calcium in contraction and relaxation, we have studied the effect of hypertonic solutions of sucrose between 1 and 6.96 times the normal tonicity in order to observe the behavior of the internal linked or free calcium of this structure, as well as to prove the hypothesis that hypertonic solutions encourage the calcium exit of the sarcoplasmatic reticulum with the resulting signs of contractures. The following results were obtained: 1. The ATP hydrolisis and calcium transport rate are 14% and 90% respectively of the maximum speeds of 10(-5) M in calcium, while for concentrations of 10(-7) M or ess of the said cation, the transport rates and the ATPase do not reach 5% of the maximum values. 2. Between 1 and 2.54 times of the normal tonicity the calcium uptake remains between 400 and 500 nmoles of calcium/mg protein/min, the transported amount of calcium varies between 14 and 16 nmoles/mg protein and the rate of the ATP hydrolysis increases a 37% to 0.4 M in sucrose. 3. Between 0.4 and 1.2 M in sucrose of 2.54 to 6.96 times the isotonicity, the calcium transport rate velocity as well as the ATP hydrolisis are strongly inhibited. The vesicles volume minimizes and the amount of linked calcium remains within the control values, proving that the capacity of linking this cathion is independent from sarcoplasmic reticulum volume. These results show that the sarcoplasmic reticulum is involved in the contractures induced by hypertonic solutions in intact cells, since the osmolarity increase produces changes of volume which results in a decrease of the calcium transportation velocity or in an increase of the exit of said cathion.

  3. Effects of Preslaughter Stress Levels on the Post-mortem Sarcoplasmic Proteomic Profile of Gilthead Seabream Muscle

    DEFF Research Database (Denmark)

    Silva, Tomé Santos; Cordeiro, Odete D; Matos, Elisabete D.

    2012-01-01

    identification was performed by MALDI-TOF-TOF MS. Analysis of the results indicates changes on several cellular pathways, with some of these changes being attributable to oxidative and proteolytic activity on sarcoplasmic proteins, together with leaking of myofibrillar proteins. These processes appear to have...

  4. Design and characterization of self-assembled fish sarcoplasmic protein-alginate nanocomplexes

    DEFF Research Database (Denmark)

    Boutrup Stephansen, Karen; Mattebjerg, Maria Ahlm; Wattjes, Jasper

    2015-01-01

    Macrostructures based on natural polymers are subject to large attention, as the application range is wide within the food and pharmaceutical industries. In this study we present nanocomplexes (NCXs) made from electrostatic self-assembly between negatively charged alginate and positively charged...... fish sarcoplasmic proteins (FSP), prepared by bulk mixing. A concentration screening revealed that there was a range of alginate and FSP concentrations where stable NCXs with similar properties were formed, rather than two exact concentrations. The size of the NCXs was 293 +/- 3 nm, and the zeta...

  5. Endoplasmic reticulum stress in lung disease

    Directory of Open Access Journals (Sweden)

    Stefan J. Marciniak

    2017-06-01

    Full Text Available Exposure to inhaled pollutants, including fine particulates and cigarette smoke is a major cause of lung disease in Europe. While it is established that inhaled pollutants have devastating effects on the genome, it is now recognised that additional effects on protein folding also drive the development of lung disease. Protein misfolding in the endoplasmic reticulum affects the pathogenesis of many diseases, ranging from pulmonary fibrosis to cancer. It is therefore important to understand how cells respond to endoplasmic reticulum stress and how this affects pulmonary tissues in disease. These insights may offer opportunities to manipulate such endoplasmic reticulum stress pathways and thereby cure lung disease.

  6. Redox regulation of calcium release in skeletal and cardiac muscle

    Directory of Open Access Journals (Sweden)

    CECILIA HIDALGO

    2002-01-01

    Full Text Available In skeletal and cardiac muscle cells, specific isoforms of the Ryanodine receptor channels mediate Ca2+ release from the sarcoplasmic reticulum. These channels are highly susceptible to redox modifications, which regulate channel activity. In this work, we studied the effects of Ca2+ (endogenous agonist and Mg2+ (endogenous inhibitor on the kinetics of Ca2+ release from sarcoplasmic reticulum vesicles isolated from skeletal or cardiac mammalian muscle. Native skeletal vesicles exhibited maximal stimulation of release kinetics by 10-20 µM [Ca2+], whereas in native cardiac vesicles, maximal stimulation of release required only 1 µM [Ca2+]. In 10 µM [Ca2+], free [Mg2+] < 0.1 mM produced marked inhibition of release from skeletal vesicles but free [Mg2+] ­ 0.8 mM did not affect release from cardiac vesicles. Incubation of skeletal or cardiac vesicles with the oxidant thimerosal increased their susceptibility to stimulation by Ca2+ and decreased the inhibitory effect of Mg2+ in skeletal vesicles. Sulfhydryl-reducing agents fully reversed the effects of thimerosal. The endogenous redox species, glutathione disulfide and S-nitrosoglutathione, also stimulated release from skeletal sarcoplasmic reticulum vesicles. In 10 µM [Ca2+], 35S-nitrosoglutathione labeled a protein fraction enriched in release channels through S-glutathiolation. Free [Mg2+] 1 mM or decreasing free [Ca2+] to the nM range prevented this reaction. Possible physiological and pathological consequences of redox modification of release channels on Ca2+ signaling in heart and muscle cells are discussed

  7. Localization and in-vivo characterization of thapsia garganica CYP76AE2 indicates a role in thapsigargin biosynthesis

    DEFF Research Database (Denmark)

    Andersen, Trine Bundgaard; Martinez-Swatson, Karen Agatha; Rasmussen, Silas Anselm

    2017-01-01

    The Mediterranean plant Thapsia garganica (dicot, Apiaceae), also known as deadly carrot, produces the highly toxic compound thapsigargin. This compound is a potent inhibitor of the sarcoplasmic-endoplasmic reticulum Ca2+ -ATPase calcium pump in mammals and is of industrial importance as the active...

  8. The structural basis of calcium transport by the calcium pump

    DEFF Research Database (Denmark)

    Olesen, Claus; Picard, Martin; Winther, Anne-Marie Lund

    2007-01-01

    The sarcoplasmic reticulum Ca2+-ATPase, a P-type ATPase, has a critical role in muscle function and metabolism. Here we present functional studies and three new crystal structures of the rabbit skeletal muscle Ca2+-ATPase, representing the phosphoenzyme intermediates associated with Ca2+ binding,...

  9. Brody disease: insights into biochemical features of SERCA1 and identification of a novel mutation.

    NARCIS (Netherlands)

    Vattemi, G.; Gualandi, F.; Oosterhof, A.; Marini, M.; Tonin, P.; Rimessi, P.; Neri, M.; Guglielmi, V.; Russignan, A.; Poli, C.; Kuppevelt, A.H.M.S.M. van; Ferlini, A.; Tomelleri, G.

    2010-01-01

    Brody disease is an inherited disorder of skeletal muscle function characterized by increasing impairment of relaxation during exercise. The autosomal recessive form can be caused by mutations in the ATP2A1 gene, which encodes for the sarcoplasmic/endoplasmic reticulum Ca-ATPase 1 (SERCA1) protein.

  10. MicroRNAs and cardiac sarcoplasmic reticulum calcium ATPase-2 in human myocardial infarction: expression and bioinformatic analysis.

    Science.gov (United States)

    Boštjančič, Emanuela; Zidar, Nina; Glavač, Damjan

    2012-10-15

    Cardiac sarco(endo)plasmic reticulum calcium ATPase-2 (SERCA2) plays one of the central roles in myocardial contractility. Both, SERCA2 mRNA and protein are reduced in myocardial infarction (MI), but the correlation has not been always observed. MicroRNAs (miRNAs) act by targeting 3'-UTR mRNA, causing translational repression in physiological and pathological conditions, including cardiovascular diseases. One of the aims of our study was to identify miRNAs that could influence SERCA2 expression in human MI. The protein SERCA2 was decreased and 43 miRNAs were deregulated in infarcted myocardium compared to corresponding remote myocardium, analyzed by western blot and microRNA microarrays, respectively. All the samples were stored as FFPE tissue and in RNAlater. miRNAs binding prediction to SERCA2 including four prediction algorithms (TargetScan, PicTar, miRanda and mirTarget2) identified 213 putative miRNAs. TAM and miRNApath annotation of deregulated miRNAs identified 18 functional and 21 diseased states related to heart diseases, and association of the half of the deregulated miRNAs to SERCA2. Free-energy of binding and flanking regions (RNA22, RNAfold) was calculated for 10 up-regulated miRNAs from microarray analysis (miR-122, miR-320a/b/c/d, miR-574-3p/-5p, miR-199a, miR-140, and miR-483), and nine miRNAs deregulated from microarray analysis were used for validation with qPCR (miR-21, miR-122, miR-126, miR-1, miR-133, miR-125a/b, and miR-98). Based on qPCR results, the comparison between FFPE and RNAlater stored tissue samples, between Sybr Green and TaqMan approaches, as well as between different reference genes were also performed. Combing all the results, we identified certain miRNAs as potential regulators of SERCA2; however, further functional studies are needed for verification. Using qPCR, we confirmed deregulation of nine miRNAs in human MI, and show that qPCR normalization strategy is important for the outcome of miRNA expression analysis in human MI.

  11. Surface Segregation in YSZ

    DEFF Research Database (Denmark)

    Bay, Lasse; Zachau-Christiansen, Birgit; Jacobsen, Torben

    1998-01-01

    The space charge layer formed due to segregation of yttria and oxygen ion vacancies in YSZ is described by a simple model. Effects of impurities segregation are omitted.......The space charge layer formed due to segregation of yttria and oxygen ion vacancies in YSZ is described by a simple model. Effects of impurities segregation are omitted....

  12. Ca2+ handling abnormalities in early-onset muscle diseases: Novel concepts and perspectives.

    NARCIS (Netherlands)

    Treves, S.; Jungbluth, H.; Voermans, N.C.; Muntoni, F.; Zorzato, F.

    2017-01-01

    The physiological process by which Ca2+ is released from the sarcoplasmic reticulum is called excitation-contraction coupling; it is initiated by an action potential which travels deep into the muscle fiber where it is sensed by the dihydropyridine receptor, a voltage sensing L-type Ca2+channel

  13. [3H]Azidodantrolene photoaffinity labeling, synthetic domain peptides and monoclonal antibody reactivity identify the dantrolene binding sequence on RyR1

    Energy Technology Data Exchange (ETDEWEB)

    Paul-Pletzer, Kalanethee; Yamamoto, Takeshi; Bhat, Manju B.; Ma, Jianjie; Ikemoto, Noriaki; Jimenez, Leslie S.; Morimoto, Hiromi; Williams, Philip G.; Parness, Jerome

    2002-06-14

    Dantrolene is a drug that suppresses intracellular Ca2+ release from sarcoplasmic reticulum in normal skeletal muscle and is used as a therapeutic agent in individuals susceptible to malignant hyperthermia. Though its precise mechanism of action has not been elucidated, we have identified the N-terminal region (amino acids 1-1400) of the skeletal muscle isoform of the ryanodine receptor (RyR1), the primary Ca2+ release channel in sarcoplasmic reticulum, as a molecular target for dantrolene using the photoaffinity analog [3H]azidodantrolene(1). Here, we demonstrate that heterologously expressed RyR1 retains its capacity to be specifically labeled with [3H]azidodantrolene,indicating that muscle specific factors are not required for this ligand-receptor interaction. Synthetic domain peptides of RyR1, previously shown to affect RyR1 function in vitro and in vivo, were exploited as potential drug binding site mimics and used in photoaffinity labeling experiments. Only DP1 and DP1-2, peptide s containing the amino acid sequence corresponding to RyR1 residues 590-609, were specifically labeled by [3H]azidodantrolene. A monoclonal anti-RyR1 antibody which recognizes RyR1 and its 1400 amino acid N-terminal fragment, recognizes DP1 and DP1-2 in both Western blots and immunoprecipitation assays, and specifically inhibits [3H]azidodantrolene photolabeling of RyR1 and its N-terminal fragment in sarcoplasmic reticulum. Our results indicate that synthetic domain peptides can mimic a native, ligand binding conformation in vitro, and that the dantrolene binding site and the epitope for the monoclonal antibody on RyR1 are equivalent and composed of amino-acids 590-609.

  14. Regulatory effects of phospholamban on cardiac sarcoplasmic reticulum function

    International Nuclear Information System (INIS)

    Kim, Hae Won.

    1989-01-01

    In this thesis, the author reports the effect of phospholamban on: (a) Ca 2+ release by cardiac SR and (b) the Ca 2+ -ATPase activity in a purified reconstituted system. Phosphorylation of phospholamban by Ca 2+ · calmodulin-dependent protein kinase had no appreciable effect on the initial rates of Ca 2+ release from cardiac SR vesicles loaded under passive conditions and on the apparent 45 Ca 2+ - 40 Ca 2+ exchange from cardiac SR vesicles loaded under active conditions. us, it appears that Ca 2+ · calmodulin-dependent phosphorylation of phospholamban is not involved in the regulation of Ca 2+ release and 45 Ca 2+-40 Ca 2+ exchange. To determine the molecular mechanism by which phospholamban regulates the Ca 2+ pump, a reconstituted system was developed, using a freeze-thaw sonication procedure. The Ca 2+ -ATPase was purified by a method which yields an active enzyme preparation essentially free of phospholamban. The best rates of Ca 2+ uptake were obtained when cholate and phosphatidylcholine (PC) were used at a ratio of cholate/PC/Ca 2 + -ATPase of 2/80/1. The maximal rates of Ca 2+ Uptake were 700 nmol/min/mg reconstituted vesicles compared to 800 nmol/min/mg SR vesicles. The EC 50 values for Ca 2+ were 0.05 μM for both Ca 2+ uptake and Ca 2+ -ATPase activity in the reconstituted vesicles compared to 0.63 μM Ca 2+ in native SR vesicles. To determine the effect of phospholamban on the Ca + -ATPase activity in the reconstituted vesicles, purified phospholamban was added to the cholate/Ca 2+ -ATPase mixture prior to combining it with liposomes

  15. The role of the endoplasmic reticulum stress response following cerebral ischemia.

    Science.gov (United States)

    Hadley, Gina; Neuhaus, Ain A; Couch, Yvonne; Beard, Daniel J; Adriaanse, Bryan A; Vekrellis, Kostas; DeLuca, Gabriele C; Papadakis, Michalis; Sutherland, Brad A; Buchan, Alastair M

    2018-06-01

    Background Cornu ammonis 3 (CA3) hippocampal neurons are resistant to global ischemia, whereas cornu ammonis (CA1) 1 neurons are vulnerable. Hamartin expression in CA3 neurons mediates this endogenous resistance via productive autophagy. Neurons lacking hamartin demonstrate exacerbated endoplasmic reticulum stress and increased cell death. We investigated endoplasmic reticulum stress responses in CA1 and CA3 regions following global cerebral ischemia, and whether pharmacological modulation of endoplasmic reticulum stress or autophagy altered neuronal viability . Methods In vivo: male Wistar rats underwent sham or 10 min of transient global cerebral ischemia. CA1 and CA3 areas were microdissected and endoplasmic reticulum stress protein expression quantified at 3 h and 12 h of reperfusion. In vitro: primary neuronal cultures (E18 Wistar rat embryos) were exposed to 2 h of oxygen and glucose deprivation or normoxia in the presence of an endoplasmic reticulum stress inducer (thapsigargin or tunicamycin), an endoplasmic reticulum stress inhibitor (salubrinal or 4-phenylbutyric acid), an autophagy inducer ([4'-(N-diethylamino) butyl]-2-chlorophenoxazine (10-NCP)) or autophagy inhibitor (3-methyladenine). Results In vivo, decreased endoplasmic reticulum stress protein expression (phospho-eIF2α and ATF4) was observed at 3 h of reperfusion in CA3 neurons following ischemia, and increased in CA1 neurons at 12 h of reperfusion. In vitro, endoplasmic reticulum stress inducers and high doses of the endoplasmic reticulum stress inhibitors also increased cell death. Both induction and inhibition of autophagy also increased cell death. Conclusion Endoplasmic reticulum stress is associated with neuronal cell death following ischemia. Neither reduction of endoplasmic reticulum stress nor induction of autophagy demonstrated neuroprotection in vitro, highlighting their complex role in neuronal biology following ischemia.

  16. A novel heterozygous mutation of the WFS1 gene leading to constitutive endoplasmic reticulum stress is the cause of Wolfram syndrome.

    Science.gov (United States)

    Morikawa, Shuntaro; Tajima, Toshihiro; Nakamura, Akie; Ishizu, Katsura; Ariga, Tadashi

    2017-12-01

    Wolfram syndrome (WS) is a disorder characterized by the association of insulin-dependent diabetes mellitus (DM), diabetes insipidus, deafness, and optic nerve atrophy. WS is caused by WFS1 mutations encoding WFS1 protein expressed in endoplasmic reticulum (ER). During ER protein synthesis, misfolded and unfolded proteins accumulate, known as "ER stress". This is attenuated by the unfolded protein response (UPR), which recovers and maintains ER functions. Because WFS1 is a UPR component, mutant WFS1 might cause unresolvable ER stress conditions and cell apoptosis, the major causes underlying WS symptoms. We encountered an 11-month-old Japanese female WS patient with insulin-dependent DM, congenital cataract and severe bilateral hearing loss. Analyze the WFS1 and functional consequence of the patient WFS1 in vitro. The patient WFS1 contained a heterozygous 4 amino acid in-frame deletion (p.N325_I328del). Her mutant WFS1 increased GRP78 and ATF6α promoter activities in the absence of thapsigargin, indicating constitutive ER stress and nuclear factor of activated T-cell reporter activity, reflecting elevated cytosolic Ca 2+ signals. Mutant transfection into cells reduced mRNA expression levels of sarcoplasmic/endoplasmic reticulum Ca 2+ transport ATPase 2b (SERCA2b) compared with wild type. Because SERCA2b is required for ER and cytoplasmic Ca 2+ homeostasis, decreased SERCA2b expression might affect ER Ca 2+ efflux, causing cell apoptosis. A novel heterozygous mutation of WFS1 induced constitutive ER stress through ATF6α activation and ER Ca 2+ efflux, resulting in cell apoptosis. These results provide new insights into the roles of WFS1 in UPR and mechanism of monogenic DM. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  17. Gender Segregation Small Firms

    OpenAIRE

    Kenneth R Troske; William J Carrington

    1992-01-01

    This paper studies interfirm gender segregation in a unique sample of small employers. We focus on small firms because previous research on interfirm segregation has studied only large firms and because it is easier to link the demographic characteristics of employers and employees in small firms. This latter feature permits an assessment of the role of employer discrimination in creating gender segregation. Our first finding is that interfirm segregation is prevalent among small employers. I...

  18. Location matters: the endoplasmic reticulum and protein trafficking in dendrites

    Directory of Open Access Journals (Sweden)

    Omar A Ramírez

    2011-01-01

    Full Text Available Neurons are highly polarized, but the trafficking mechanisms that operate in these cells and the topological organization of their secretory organelles are still poorly understood. Particularly incipient is our knowledge of the role of the neuronal endoplasmic reticulum. Here we review the current understanding of the endoplasmic reticulum in neurons, its structure, composition, dendritic distribution and dynamics. We also focus on the trafficking of proteins through the dendritic endoplasmic reticulum, emphasizing the relevance of transport, retention, assembly of multi-subunit protein complexes and export. We additionally discuss the roles of the dendritic endoplasmic reticulum in synaptic plasticity.

  19. Morphological and Biochemical Characterization of Bovine Congenital Psudomyotonia

    OpenAIRE

    Dorotea, Tiziano

    2015-01-01

    The Ca2+-ATPase of sarco(endo)plasmic reticulum (SERCA) is a protein of about 110 kDa member of the P-type ATPases family. SERCA pumps utilize the energy derived from the hydrolysis of a molecule of ATP to transport two Ca2+ ions across the Sarcoplasmic Reticulum (SR) membrane to decrease the Ca2+ concentration in the cytosol. SERCA isoform 1a (SERCA1a) is the mainly expressed isoform in adult fast-twitch muscle fibre and it is both structurally and functionally the best characterized member ...

  20. Plasmid segregation mechanisms

    DEFF Research Database (Denmark)

    Ebersbach, G.; Gerdes, Kenn

    2005-01-01

    Bacterial plasmids encode partitioning (par) loci that ensure ordered plasmid segregation prior to cell division. par loci come in two types: those that encode actin-like ATPases and those that encode deviant Walker-type ATPases. ParM, the actin-like ATPase of plasmid R1, forms dynamic filaments...... that segregate plasmids paired at mid-cell to daughter cells. Like microtubules, ParM filaments exhibit dynamic instability (i.e., catastrophic decay) whose regulation is an important component of the DNA segregation process. The Walker box ParA ATPases are related to MinD and form highly dynamic, oscillating...... filaments that are required for the subcellular movement and positioning of plasmids. The role of the observed ATPase oscillation is not yet understood. However, we propose a simple model that couples plasmid segregation to ParA oscillation. The model is consistent with the observed movement...

  1. Applied Thermodynamics: Grain Boundary Segregation

    Directory of Open Access Journals (Sweden)

    Pavel Lejček

    2014-03-01

    Full Text Available Chemical composition of interfaces—free surfaces and grain boundaries—is generally described by the Langmuir–McLean segregation isotherm controlled by Gibbs energy of segregation. Various components of the Gibbs energy of segregation, the standard and the excess ones as well as other thermodynamic state functions—enthalpy, entropy and volume—of interfacial segregation are derived and their physical meaning is elucidated. The importance of the thermodynamic state functions of grain boundary segregation, their dependence on volume solid solubility, mutual solute–solute interaction and pressure effect in ferrous alloys is demonstrated.

  2. C[sub 10]-O[sub eq]-N-(4-azido-5-[sup 125]iodo salicyloyl)-[beta]-alanyl-[beta] alanyl ryanodine (Az-[beta]AR), a novel photo-affinity ligand for the ryanodine binding site

    Energy Technology Data Exchange (ETDEWEB)

    Bidasee, K.R.; Besch, H.R. Jr.; Kwon, Sangyeol; Emmick, J.T.; Besch, K.T.; Gerzon, Koert; Humerickhouse, R.A. (Indiana Univ., Indianapolis, IN (United States). School of Medicine)

    1994-01-01

    A high affinity, photoactivatable, radio-iodinated ligand for the ryanodine binding site(s) of the sarcoplasmic reticulum calcium-release channel, C[sub 10]-O[sub e]-N-(4-azido-5-[sup 125]iodo salicyloyl)-[beta]-alanyl-[beta]-alanyl ryanodine (Az-[beta]AR), was synthesized at a specific activity of 1400mCi/mmol. (Author).

  3. Chromosome segregation in plant meiosis

    Directory of Open Access Journals (Sweden)

    Linda eZamariola

    2014-06-01

    Full Text Available Faithful chromosome segregation in meiosis is essential for ploidy stability over sexual life cycles. In plants, defective chromosome segregation caused by gene mutations or other factors leads to the formation of unbalanced or unreduced gametes creating aneuploid or polyploid progeny, respectively. Accurate segregation requires the coordinated execution of conserved processes occurring throughout the two meiotic cell divisions. Synapsis and recombination ensure the establishment of chiasmata that hold homologous chromosomes together allowing their correct segregation in the first meiotic division, which is also tightly regulated by cell-cycle dependent release of cohesin and monopolar attachment of sister kinetochores to microtubules. In meiosis II, bi-orientation of sister kinetochores and proper spindle orientation correctly segregate chromosomes in four haploid cells. Checkpoint mechanisms acting at kinetochores control the accuracy of kinetochore-microtubule attachment, thus ensuring the completion of segregation. Here we review the current knowledge on the processes taking place during chromosome segregation in plant meiosis, focusing on the characterization of the molecular factors involved.

  4. A conformation-specific interhelical salt bridge in the K+ binding site of gastric H,K-ATPase

    NARCIS (Netherlands)

    Koenderink, J.B.; Swarts, H.G.P.; Willems, P.H.G.M.; Krieger, E.; Pont, J.J.H.H.M. de

    2004-01-01

    Homology modeling of gastric H, K-ATPase based on the E-2 model of sarcoplasmic reticulum Ca2+-ATPase (Toyoshima, C., and Nomura, H. (2002) Nature 392, 835-839) revealed the presence of a single high-affinity binding site for K+ and an E-2 form-specific salt bridge between Glu(820) (M6) and Lys(791)

  5. A conformation-specific interhelical salt bridge in the K+ binding site of gastric H,K-ATPase.

    NARCIS (Netherlands)

    Koenderink, J.B.; Swarts, H.G.P.; Willems, P.H.G.M.; Krieger, E.; Pont, J.J.H.H.M. de

    2004-01-01

    Homology modeling of gastric H,K-ATPase based on the E2 model of sarcoplasmic reticulum Ca2+-ATPase (Toyoshima, C., and Nomura, H. (2002) Nature 392, 835-839) revealed the presence of a single high-affinity binding site for K+ and an E2 form-specific salt bridge between Glu820 (M6) and Lys791 (M5).

  6. Understanding Segregation Processes

    Science.gov (United States)

    Bruch, Elizabeth

    There is growing consensus that living in neighborhoods of concentrated poverty increases the likelihood of social problems such as teenage parenthood, drug and alcohol use, crime victimization, and chronic unemployment. Neighborhood inequality is also implicated in studies of enduring race/ethnic health disparities, and there are recent moves to broaden the definition of health care policy to policies targeting social inequality (Mechanic 2007). Residential segregation affects health outcomes in several different ways. First, income, education, and occupation are all strongly related to health (Adler and Newman 2002). Segregation is a key mechanism through which socioeconomic inequality is perpetuated and reinforced, as it hinders the upward mobility of disadvantaged groups by limiting their educational and employment opportunities. Second, segregation increases minority exposure to unhealthy neighborhood environments. Residential segregation creates areas with concentrated poverty and unemployment, both of which are key factors that predict violence and create racial differences in homicide (Samson and Wilson 1995). Neighborhood characteristics, such as exposure to environmental hazards, fear of violence, and access to grocery stores, affect health risks and health behaviors (Cheadle et al. 1991). Tobacco and alcohol industries also advertise their products disproportionately in poor, minority areas (Moore, Williams, and Qualls 1996). Finally, residential segregation leads to inequalitie in health care resources, which contributes to disparities in quality of treatment (Smedley, Stith, and Nelson 2002).

  7. Conditions for spatial segregation: some European perspectives.

    NARCIS (Netherlands)

    Musterd, S.; de Winter, M.

    1998-01-01

    Evaluates some theses on the theme of spatial segregation in Europe. Spatial segregation as an important issue on the political agendas of European nations; Two views of segregation in Europe; Strategies of European nations to deal with segregation; Segregation in European cities

  8. Segregation and Hispanic Homicide

    Directory of Open Access Journals (Sweden)

    Michael G. Bisciglia

    2014-01-01

    Full Text Available As the overall population of Hispanics within the United States has eclipsed that of African Americans, a mounting concern has developed regarding the rise in Hispanic lethal violence as a result of social and economic inequality. One means to measure this inequality is in the form of segregation. Research indicates that in many Hispanic communities, their levels of segregation from the White non-Hispanic population are similar to that of African Americans. Although a multitude of previous studies have looked at the impact of segregation among African Americans, the literature remains under-represented in terms of multi-city macro-level analyses among Hispanics. This current study extends the analysis of segregation’s effects on lethal violence to this population. To this end, two measures of segregation were used, the index of dissimilarity and exposure. Using data from the census and the Centers for Disease Control (CDC mortality files, negative binominal regression models were created using a sample of 236 U.S. cities. The results indicated that both measures of segregation show a strong positive influence on rates of Hispanic homicides.

  9. 1H nuclear magnetic resonance studies of sarcoplasmic oxygenation in the red cell-perfused rat heart

    OpenAIRE

    Jelicks, L.A.; Wittenberg, B.A.

    1995-01-01

    The proximal histidine N delta H proton of deoxymyoglobin experiences a large hyperfine shift resulting in its 1H nuclear magnetic resonance (NMR) signal appearing at approximately 76 ppm (at 35 degrees C), downfield of the diamagnetic spectral region. 1H NMR of this proton is used to monitor sarcoplasmic oxygen pressure in isolated perfused rat heart. This method monitors intracellular oxygenation in the whole heart and does not reflect oxygenation in a limited region. The deoxymyoglobin res...

  10. Waste segregation procedures and benefits

    International Nuclear Information System (INIS)

    Fish, J.D.; Massey, C.D.; Ward, S.J.

    1990-01-01

    Segregation is a critical first step in handling hazardous and radioactive materials to minimize the generation of regulated wastes. In addition, segregation can significantly reduce the complexity and the total cost of managing waste. Procedures at Sandia National Laboratories, Albuquerque require that wastes be segregated, first, by waste type (acids, solvents, low level radioactive, mixed, classified, etc.). Higher level segregation requirements, currently under development, are aimed at enhancing the possibilities for recovery, recycle and reapplication; reducing waste volumes; reducing waste disposal costs, and facilitating packaging storage, shipping and disposal. 2 tabs

  11. Prediction of endoplasmic reticulum resident proteins using fragmented amino acid composition and support vector machine

    Directory of Open Access Journals (Sweden)

    Ravindra Kumar

    2017-09-01

    Full Text Available Background The endoplasmic reticulum plays an important role in many cellular processes, which includes protein synthesis, folding and post-translational processing of newly synthesized proteins. It is also the site for quality control of misfolded proteins and entry point of extracellular proteins to the secretory pathway. Hence at any given point of time, endoplasmic reticulum contains two different cohorts of proteins, (i proteins involved in endoplasmic reticulum-specific function, which reside in the lumen of the endoplasmic reticulum, called as endoplasmic reticulum resident proteins and (ii proteins which are in process of moving to the extracellular space. Thus, endoplasmic reticulum resident proteins must somehow be distinguished from newly synthesized secretory proteins, which pass through the endoplasmic reticulum on their way out of the cell. Approximately only 50% of the proteins used in this study as training data had endoplasmic reticulum retention signal, which shows that these signals are not essentially present in all endoplasmic reticulum resident proteins. This also strongly indicates the role of additional factors in retention of endoplasmic reticulum-specific proteins inside the endoplasmic reticulum. Methods This is a support vector machine based method, where we had used different forms of protein features as inputs for support vector machine to develop the prediction models. During training leave-one-out approach of cross-validation was used. Maximum performance was obtained with a combination of amino acid compositions of different part of proteins. Results In this study, we have reported a novel support vector machine based method for predicting endoplasmic reticulum resident proteins, named as ERPred. During training we achieved a maximum accuracy of 81.42% with leave-one-out approach of cross-validation. When evaluated on independent dataset, ERPred did prediction with sensitivity of 72.31% and specificity of 83

  12. Cardiac function improved by sarcoplasmic reticulum Ca2+-ATPase overexpression in a heart failure model induced by chronic myocardial ischemia

    Directory of Open Access Journals (Sweden)

    Wei XIN

    2011-04-01

    Full Text Available Objective Chronic myocardial ischemia(CMI has become an important cause of heart failure(HF.The aim of present study was to examine the effects of Sarco-endoplasmic reticulum calcium ATPase(SERCA2a gene transfer in HF model in large animal induced by CMI.Methods HF was reproduced in minipigs by ligating the initial segment of proximal left anterior descending(LAD coronary artery with an ameroid constrictor to produce progressive vessel occlusion and ischemia.After confirmation of myocardial perfusion defect and cardiac function impairment by SPECT and echocardiography in the model,animals were divided into 4 groups: HF group;HF+enhanced green fluorescent protein(EGFP group;HF+SERCA2a group;and sham operation group as control.rAAV1-EGFP and rAAV1-SERCA2a(1×1012 vg for each animal were directly and intramyocardially injected to the animals of HF+EGFP and HF+SERCA2a groups.Sixty days after the gene transfer,the expression of SERCA2a at the protein level was examined by Western blotting and immunohistochemistry,the changes in cardiac function were determined by echocardiographic and hemodynamic analysis,and the changes in serum inflammatory and neuro-hormonal factors(including BNP,TNF-a,IL-6,ET-1 and Ang II were determined by radioimmunoassay.Results Sixty days after gene transfer,LVEF,Ev/Av and ±dp/dtmax increased significantly(P < 0.05,along with an increase of SERCA2a protein expression in the ischemic myocardium(PP < 0.05,accompanied by a significant decrease of inflammatory and neural-hormonal factors(PP < 0.05 in HF+SERCA2a group as compared with HF/HF+EGFP group.Conclusions Overexpression of SERCA2a may significantly improve the cardiac function of the ischemic myocardium of HF model induced by CMI and reverse the activation of neural-hormonal factors,implying that it has a potential therapeutic significance in CMI related heart failure.

  13. Racial Residential Segregation: Measuring Location Choice Attributes of Environmental Quality and Self-Segregation

    Directory of Open Access Journals (Sweden)

    Zhaohua Zhang

    2018-04-01

    Full Text Available Both sorting on public goods and tastes for segregation contribute to the persistence of segregation in America. Incorporating Schelling’s (1969, 1971 concept of “neighborhood tipping” into a two-stage equilibrium sorting model, in which both neighborhood demographic composition and public goods (e.g., environmental quality affect households’ residential location choice, this study investigates how preferences for neighborhood demographic composition could obscure the role of exogenous public goods on segregation. The results reveal that non-white households face higher level of exposure to air pollution, suggesting the presence of environmental injustice in Franklin County, OH. Using a counterfactual scenario of switching off heterogeneous taste for environmental quality, this study identifies that sorting on Toxic Release Inventory (TRI emissions drives little correlations between emissions and demographics. However, when taste parameters of the interactions between neighborhood demographic composition and household race are eliminated, segregation (as measured by over-exposure to households of the same race of black and white households decreases by 7.63% and 16.36%, respectively, and own-race neighbor preferences contribute to segregation differently according to household income. These results may help explain some recent puzzles in the relationship between environmental quality and demographics.

  14. Calcium release-dependent inactivation precedes formation of the tubular system in developing rat cardiac myocytes.

    Science.gov (United States)

    Macková, Katarina; Zahradníková, Alexandra; Hoťka, Matej; Hoffmannová, Barbora; Zahradník, Ivan; Zahradníková, Alexandra

    2017-12-01

    Developing cardiac myocytes undergo substantial structural and functional changes transforming the mechanism of excitation-contraction coupling from the embryonic form, based on calcium influx through sarcolemmal DHPR calcium channels, to the adult form, relying on local calcium release through RYR calcium channels of sarcoplasmic reticulum stimulated by calcium influx. We characterized day-by-day the postnatal development of the structure of sarcolemma, using techniques of confocal fluorescence microscopy, and the development of the calcium current, measured by the whole-cell patch-clamp in isolated rat ventricular myocytes. We characterized the appearance and expansion of the t-tubule system and compared it with the appearance and progress of the calcium current inactivation induced by the release of calcium ions from sarcoplasmic reticulum as structural and functional measures of direct DHPR-RYR interaction. The release-dependent inactivation of calcium current preceded the development of the t-tubular system by several days, indicating formation of the first DHPR-RYR couplons at the surface sarcolemma and their later spreading close to contractile myofibrils with the growing t-tubules. Large variability of both of the measured parameters among individual myocytes indicates uneven maturation of myocytes within the growing myocardium.

  15. Segregation and civic virtue

    NARCIS (Netherlands)

    Merry, M.S.

    2012-01-01

    In this essay Michael Merry defends the following prima facie argument: that civic virtue is not dependent on integration and in fact may be best fostered under conditions of segregation. He demonstrates that civic virtue can and does take place under conditions of involuntary segregation, but that

  16. Gender Differences in the Effect of Residential Segregation on Workplace Segregation among Newly Arrived Immigrants

    OpenAIRE

    Tammaru, Tiit; Strömgren, Magnus; van Ham, Maarten; Danzer, Alexander M.

    2015-01-01

    Contemporary cities are becoming more and more diverse in population as a result of immigration. Research also shows that within cities residential neighborhoods are becoming ethnically more diverse, but that residential segregation has remained persistently high. High levels of segregation are often seen as negative, preventing integration of immigrants in their host society and having a negative impact on people's lives. Segregation research often focuses on residential neighborhoods, but i...

  17. Income Segregation between Schools and School Districts

    Science.gov (United States)

    Owens, Ann; Reardon, Sean F.; Jencks, Christopher

    2016-01-01

    Although trends in the racial segregation of schools are well documented, less is known about trends in income segregation. We use multiple data sources to document trends in income segregation between schools and school districts. Between-district income segregation of families with children enrolled in public school increased by over 15% from…

  18. Inhibition of sarcoplasmic Ca2+-ATPase increases caffeine- and halothane-induced contractures in muscle bundles of malignant hyperthermia susceptible and healthy individuals

    Directory of Open Access Journals (Sweden)

    Roewer Norbert

    2005-06-01

    Full Text Available Abstract Background Malignant hyperthermia (MH is triggered by halogenated anaesthetics and depolarising muscle relaxants, leading to an uncontrolled hypermetabolic state of skeletal muscle. An uncontrolled sarcoplasmic Ca2+ release is mediated via the ryanodine receptor. A compensatory mechanism of increased sarcoplasmic Ca2+-ATPase activity was described in pigs and in transfected cell lines. We hypothesized that inhibition of Ca2+ reuptake via the sarcoplasmic Ca2+-ATPase (SERCA enhances halothane- and caffeine-induced muscle contractures in MH susceptible more than in non-susceptible skeletal muscle. Methods With informed consent, surplus muscle bundles of 7 MHS (susceptible, 7 MHE (equivocal and 16 MHN (non-susceptible classified patients were mounted to an isometric force transducer, electrically stimulated, preloaded and equilibrated. Following 15 min incubation with cyclopiazonic acid (CPA 25 μM, the European MH standard in-vitro-contracture test protocol with caffeine (0.5; 1; 1.5; 2; 3; 4 mM and halothane (0.11; 0.22; 0.44; 0.66 mM was performed. Data as median and quartiles; Friedman- and Wilcoxon-test for differences with and without CPA; p Results Initial length, weight, maximum twitch height, predrug resting tension and predrug twitch height of muscle bundles did not differ between groups. CPA increased halothane- and caffeine-induced contractures significantly. This increase was more pronounced in MHS and MHE than in MHN muscle bundles. Conclusion Inhibition of the SERCA activity by CPA enhances halothane- and caffeine-induced contractures especially in MHS and MHE skeletal muscle and may help for the diagnostic assignment of MH susceptibility. The status of SERCA activity may play a significant but so far unknown role in the genesis of malignant hyperthermia.

  19. 36 CFR 254.6 - Segregative effect.

    Science.gov (United States)

    2010-07-01

    ... 36 Parks, Forests, and Public Property 2 2010-07-01 2010-07-01 false Segregative effect. 254.6... ADJUSTMENTS Land Exchanges § 254.6 Segregative effect. (a) If a proposal is made to exchange Federal lands... segregative effect terminates as follows: (1) Automatically, upon issuance of a patent or other document of...

  20. Grain boundary segregation and intergranular failure

    International Nuclear Information System (INIS)

    White, C.L.

    1980-01-01

    Trace elements and impurities often segregate strongly to grain boundaries in metals and alloys. Concentrations of these elements at grain boundaries are often 10 3 to 10 5 times as great as their overall concentration in the alloy. Because of such segregation, certain trace elements can exert a disproportionate influence on material properties. One frequently observed consequence of trace element segregation to grain boundaries is the occurrence of grain boundary failure and low ductility. Less well known are incidences of improved ductility and inhibition of grain boundary fracture resulting from trace element segregation to grain boundaries in certain systems. An overview of trace element segregation and intergranular failure in a variety of alloy systems as well as preliminary results from studies on Al 3% Li will be presented

  1. Progressive segregation of the Escherichia coli chromosome

    DEFF Research Database (Denmark)

    Nielsen, Henrik Jørck; Youngren, Brenda; Hansen, Flemming G.

    2006-01-01

    We have followed the fate of 14 different loci around the Escherichia coli chromosome in living cells at slow growth rate using a highly efficient labelling system and automated measurements. Loci are segregated as they are replicated, but with a marked delay. Most markers segregate in a smooth...... temporal progression from origin to terminus. Thus, the overall pattern is one of continuous segregation during replication and is not consistent with recently published models invoking extensive sister chromosome cohesion followed by simultaneous segregation of the bulk of the chromosome. The terminus......, and a region immediately clockwise from the origin, are exceptions to the overall pattern and are subjected to a more extensive delay prior to segregation. The origin region and nearby loci are replicated and segregated from the cell centre, later markers from the various positions where they lie...

  2. Altered Elementary Calcium Release Events and Enhanced Calcium Release by Thymol in Rat Skeletal Muscle

    OpenAIRE

    Szentesi, Péter; Szappanos, Henrietta; Szegedi, Csaba; Gönczi, Monika; Jona, István; Cseri, Julianna; Kovács, László; Csernoch, László

    2004-01-01

    The effects of thymol on steps of excitation-contraction coupling were studied on fast-twitch muscles of rodents. Thymol was found to increase the depolarization-induced release of calcium from the sarcoplasmic reticulum, which could not be attributed to a decreased calcium-dependent inactivation of calcium release channels/ryanodine receptors or altered intramembrane charge movement, but rather to a more efficient coupling of depolarization to channel opening. Thymol increased ryanodine bind...

  3. Recovery of Action Potentials and Twitches after K-contractures in Frog Skeletal Muscle(Physiology)

    OpenAIRE

    Atsuko, Suzuki; Ibuki, Shirakawa; Kazunari, Noguchi; Hirohiko, Kishi; Haruo, Sugi; Department of Physiology, School of Medicine, Teikyo University:(Present office)Department of Physical Therapy, Health Science University; Department of Physiology, School of Medicine, Teikyo University; Department of Physiology, School of Medicine, Teikyo University; Department of Physiology, School of Medicine, Teikyo University; Department of Physiology, School of Medicine, Teikyo University

    2004-01-01

    To give information about intracellular Ca^ translocation during and after K-contractures in vertebrate skeletal muscle fibers, we examined recovery of action potentials and twitches after interruption and spontaneous relaxation of K-contractures at low temperature (3℃) that greatly reduced the rate of Ca^ reuptake by the sarcoplasmic reticulum. On membrane repolarization interrupting K-contractures, the amplitude of both action potentials and twitches recovered quickly, while the falling pha...

  4. A protein interaction mechanism for suppressing the mechanosensitive Piezo channels

    OpenAIRE

    Zhang, Tingxin; Chi, Shaopeng; Jiang, Fan; Zhao, Qiancheng; Xiao, Bailong

    2017-01-01

    Piezo proteins are bona fide mammalian mechanotransduction channels for various cell types including endothelial cells. The mouse Piezo1 of 2547 residues forms a three-bladed, propeller-like homo-trimer comprising a central pore-module and three propeller-structures that might serve as mechanotransduction-modules. However, the mechanogating and regulation of Piezo channels remain unclear. Here we identify the sarcoplasmic /endoplasmic-reticulum Ca2+ ATPase (SERCA), including the widely expres...

  5. Segregation and Hispanic Homicide

    OpenAIRE

    Michael G. Bisciglia

    2014-01-01

    As the overall population of Hispanics within the United States has eclipsed that of African Americans, a mounting concern has developed regarding the rise in Hispanic lethal violence as a result of social and economic inequality. One means to measure this inequality is in the form of segregation. Research indicates that in many Hispanic communities, their levels of segregation from the White non-Hispanic population ar...

  6. Mechanisms of time-based figure-ground segregation.

    Science.gov (United States)

    Kandil, Farid I; Fahle, Manfred

    2003-11-01

    Figure-ground segregation can rely on purely temporal information, that is, on short temporal delays between positional changes of elements in figure and ground (Kandil, F.I. & Fahle, M. (2001) Eur. J. Neurosci., 13, 2004-2008). Here, we investigate the underlying mechanisms by measuring temporal segregation thresholds for various kinds of motion cues. Segregation can rely on monocular first-order motion (based on luminance modulation) and second-order motion cues (contrast modulation) with a high temporal resolution of approximately 20 ms. The mechanism can also use isoluminant motion with a reduced temporal resolution of 60 ms. Figure-ground segregation can be achieved even at presentation frequencies too high for human subjects to inspect successive frames individually. In contrast, when stimuli are presented dichoptically, i.e. separately to both eyes, subjects are unable to perceive any segregation, irrespective of temporal frequency. We propose that segregation in these displays is detected by a mechanism consisting of at least two stages. On the first level, standard motion or flicker detectors signal local positional changes (flips). On the second level, a segregation mechanism combines the local activities of the low-level detectors with high temporal precision. Our findings suggest that the segregation mechanism can rely on monocular detectors but not on binocular mechanisms. Moreover, the results oppose the idea that segregation in these displays is achieved by motion detectors of a higher order (motion-from-motion), but favour mechanisms sensitive to short temporal delays even without activation of higher-order motion detectors.

  7. Aggregation and retention of human urokinase type plasminogen activator in the yeast endoplasmic reticulum

    Directory of Open Access Journals (Sweden)

    Smirnov Vladimir N

    2002-10-01

    Full Text Available Abstract Background Secretion of recombinant proteins in yeast can be affected by their improper folding in the endoplasmic reticulum and subsequent elimination of the misfolded molecules via the endoplasmic reticulum associated protein degradation pathway. Recombinant proteins can also be degraded by the vacuolar protease complex. Human urokinase type plasminogen activator (uPA is poorly secreted by yeast but the mechanisms interfering with its secretion are largely unknown. Results We show that in Hansenula polymorpha overexpression worsens uPA secretion and stimulates its intracellular aggregation. The absence of the Golgi modifications in accumulated uPA suggests that aggregation occurs within the endoplasmic reticulum. Deletion analysis has shown that the N-terminal domains were responsible for poor uPA secretion and propensity to aggregate. Mutation abolishing N-glycosylation decreased the efficiency of uPA secretion and increased its aggregation degree. Retention of uPA in the endoplasmic reticulum stimulates its aggregation. Conclusions The data obtained demonstrate that defect of uPA secretion in yeast is related to its retention in the endoplasmic reticulum. Accumulation of uPA within the endoplasmic reticulum disturbs its proper folding and leads to formation of high molecular weight aggregates.

  8. Continuum modelling of segregating tridisperse granular chute flow

    Science.gov (United States)

    Deng, Zhekai; Umbanhowar, Paul B.; Ottino, Julio M.; Lueptow, Richard M.

    2018-03-01

    Segregation and mixing of size multidisperse granular materials remain challenging problems in many industrial applications. In this paper, we apply a continuum-based model that captures the effects of segregation, diffusion and advection for size tridisperse granular flow in quasi-two-dimensional chute flow. The model uses the kinematics of the flow and other physical parameters such as the diffusion coefficient and the percolation length scale, quantities that can be determined directly from experiment, simulation or theory and that are not arbitrarily adjustable. The predictions from the model are consistent with experimentally validated discrete element method (DEM) simulations over a wide range of flow conditions and particle sizes. The degree of segregation depends on the Péclet number, Pe, defined as the ratio of the segregation rate to the diffusion rate, the relative segregation strength κij between particle species i and j, and a characteristic length L, which is determined by the strength of segregation between smallest and largest particles. A parametric study of particle size, κij, Pe and L demonstrates how particle segregation patterns depend on the interplay of advection, segregation and diffusion. Finally, the segregation pattern is also affected by the velocity profile and the degree of basal slip at the chute surface. The model is applicable to different flow geometries, and should be easily adapted to segregation driven by other particle properties such as density and shape.

  9. Shaping Segregation: Convexity vs. concavity

    NARCIS (Netherlands)

    Gonzalez Briones, Sebastián; Windows-Yule, Kit; Luding, Stefan; Parker, D.J.; Thornton, Anthony Richard

    2014-01-01

    Controlling segregation is both a practical and a theoretical challenge. In this Letter we demonstrate a manner in which rotation-induced segregation may be controlled by altering the geometry of the rotating containers in which granular systems are housed. Using a novel drum design comprising

  10. Endoplasmic reticulum stress in pathogenesis of diabetic retinopathy and effect of calcium dobesilate

    Institute of Scientific and Technical Information of China (English)

    Yu-Min Gui; Ming Zhao; Jie Ding

    2016-01-01

    Objective:To study the mechanism of endoplasmic reticulum stress in the pathogenesis of diabetic retinopathy and effect of calcium dobesilate.Methods:A total of 120 diabetic retinopathy patients treated in our hospital from January 2010 to September 2015 were enrolled in this article. The serum endoplasmic reticulum stress protein and interleukin protein expression levels were analyzed before and after calcium dobesilate treatment. A total of 55 cases of healthy subjects receiving physical examination in our hospital during the same period were taken as control group.Results:Serum endoplasmic reticulum stress proteins PERK, CHOP and IRE as well as interleukin proteins IL1, IL2, IL6 and IL10 expression significantly increased, serum MDA level significantly increased while SOD, CAT and GSHpx levels significantly decreased in diabetic retinopathy patients, and compared with control group (P<0.01); after calcium dobesilate treatment, above factors were significantly restored (P<0.01).Conclusions: Diabetic retinopathy is closely related to endoplasmic reticulum stress and calcium dobesilate treatment may improve diabetic retinopathy by inhibiting endoplasmic reticulum stress.

  11. Image segregation in strabismic amblyopia.

    Science.gov (United States)

    Levi, Dennis M

    2007-06-01

    Humans with naturally occurring amblyopia show deficits thought to involve mechanisms downstream of V1. These include excessive crowding, abnormal global image processing, spatial sampling and symmetry detection and undercounting. Several recent studies suggest that humans with naturally occurring amblyopia show deficits in global image segregation. The current experiments were designed to study figure-ground segregation in amblyopic observers with documented deficits in crowding, symmetry detection, spatial sampling and counting, using similar stimuli. Observers had to discriminate the orientation of a figure (an "E"-like pattern made up of 17 horizontal Gabor patches), embedded in a 7x7 array of Gabor patches. When the 32 "background" patches are vertical, the "E" pops-out, due to segregation by orientation and performance is perfect; however, if the background patches are all, or mostly horizontal, the "E" is camouflaged, and performance is random. Using a method of constant stimuli, we varied the number of "background" patches that were vertical and measured the probability of correct discrimination of the global orientation of the E (up/down/left/right). Surprisingly, amblyopes who showed strong crowding and deficits in symmetry detection and counting, perform normally or very nearly so in this segregation task. I therefore conclude that these deficits are not a consequence of abnormal segregation of figure from background.

  12. Observation of endoplasmic reticulum tubules via TOF-SIMS tandem mass spectrometry imaging of transfected cells.

    Science.gov (United States)

    Chini, Corryn E; Fisher, Gregory L; Johnson, Ben; Tamkun, Michael M; Kraft, Mary L

    2018-02-26

    Advances in three-dimensional secondary ion mass spectrometry (SIMS) imaging have enabled visualizing the subcellular distributions of various lipid species within individual cells. However, the difficulty of locating organelles using SIMS limits efforts to study their lipid compositions. Here, the authors have assessed whether endoplasmic reticulum (ER)-Tracker Blue White DPX ® , which is a commercially available stain for visualizing the endoplasmic reticulum using fluorescence microscopy, produces distinctive ions that can be used to locate the endoplasmic reticulum using SIMS. Time-of-flight-SIMS tandem mass spectrometry (MS 2 ) imaging was used to identify positively and negatively charged ions produced by the ER-Tracker stain. Then, these ions were used to localize the stain and thus the endoplasmic reticulum, within individual human embryonic kidney cells that contained higher numbers of endoplasmic reticulum-plasma membrane junctions on their surfaces. By performing MS 2 imaging of selected ions in parallel with the precursor ion (MS 1 ) imaging, the authors detected a chemical interference native to the cell at the same nominal mass as the pentafluorophenyl fragment from the ER-Tracker stain. Nonetheless, the fluorine secondary ions produced by the ER-Tracker stain provided a distinctive signal that enabled locating the endoplasmic reticulum using SIMS. This simple strategy for visualizing the endoplasmic reticulum in individual cells using SIMS could be combined with existing SIMS methodologies for imaging intracellular lipid distribution and to study the lipid composition within the endoplasmic reticulum.

  13. Endoplasmic Reticulum Stress and Associated ROS

    Directory of Open Access Journals (Sweden)

    Hafiz Maher Ali Zeeshan

    2016-03-01

    Full Text Available The endoplasmic reticulum (ER is a fascinating network of tubules through which secretory and transmembrane proteins enter unfolded and exit as either folded or misfolded proteins, after which they are directed either toward other organelles or to degradation, respectively. The ER redox environment dictates the fate of entering proteins, and the level of redox signaling mediators modulates the level of reactive oxygen species (ROS. Accumulating evidence suggests the interrelation of ER stress and ROS with redox signaling mediators such as protein disulfide isomerase (PDI-endoplasmic reticulum oxidoreductin (ERO-1, glutathione (GSH/glutathione disuphide (GSSG, NADPH oxidase 4 (Nox4, NADPH-P450 reductase (NPR, and calcium. Here, we reviewed persistent ER stress and protein misfolding-initiated ROS cascades and their significant roles in the pathogenesis of multiple human disorders, including neurodegenerative diseases, diabetes mellitus, atherosclerosis, inflammation, ischemia, and kidney and liver diseases.

  14. 41 CFR 60-1.8 - Segregated facilities.

    Science.gov (United States)

    2010-07-01

    ... 41 Public Contracts and Property Management 1 2010-07-01 2010-07-01 true Segregated facilities. 60...; Compliance Reports § 60-1.8 Segregated facilities. To comply with its obligations under the Order, a contractor must ensure that facilities provided for employees are provided in such a manner that segregation...

  15. Membrane defect in procine malignant hyperthermia

    International Nuclear Information System (INIS)

    O'Brien, P.J.

    1985-01-01

    Malignant hyperthermia (MH) has been proposed to result from abnormal calcium-homeostasis in skeletal muscle. This study tested the hypothesis that calcium-sequestration or calcium-release by sarcoplasmic reticulum was abnormal in MH-susceptible swine. A heavy sarcoplasmic reticulum fraction (HSR), enriched in terminal cisternae, was isolated from MH and control muscle using differential and density-gradient centrifugation. Calcium transport was studied using 45 Ca radioisotope and Millipore filtration. Enzymatic activities, cholesterol, phospholipid, and protein composition were determined using spectrophotometric techniques and polyacrylamide gel electrophoresis. Properties of calcium-sequestration by MH and control HSR were indistinguishable, although Ca 2+ -ATPase and calsequestrin content were 100% increased in MH HSR. However when muscle homogenate pH was decreased due to MH, calcium-uptake activity was depressed to <5% of control values. Results of this study indicate a model for the etiopathogenesis of MH, and for the inheritance and diagnosis of susceptibility to MH. Malignant hyperthermia is initiated due to a hypersensitive HSR calcium-release mechanism and propagated by a loss of calcium-sequestering function as acidosis develops. Susceptibility is inherited in an autosomal, codominant pattern and may be diagnosed most definitively and sensitively on the basis of calcium-release sensitivity-tests, performed on isolated HSR

  16. Are segregated sports classes scientifically justified?

    OpenAIRE

    Lawson, Sian; Hall, Edward

    2014-01-01

    School sports classes are a key part of physical and mental development, yet in many countries these classes are gender segregated. Before institutionalised segregation can be condoned it is important to tackle assumptions and check for an evidence-based rationale. This presentation aims to analyse the key arguments for segregation given in comment-form response to a recent media article discussing mixed school sports (Lawson, 2013).\\ud \\ud The primary argument given was division for strength...

  17. Integrated schools, segregated curriculum: effects of within-school segregation on adolescent health behaviors and educational aspirations.

    Science.gov (United States)

    Walsemann, Katrina M; Bell, Bethany A

    2010-09-01

    We examined the extent to which within-school segregation, as measured by unevenness in the distribution of Black and White adolescents across levels of the English curriculum (advanced placement-international baccalaureate-honors, general, remedial, or no English), was associated with smoking, drinking, and educational aspirations, which previous studies found are related to school racial/ethnic composition. We analyzed data from wave 1 of the National Longitudinal Study of Adolescent Health, restricting our sample to non-Hispanic Blacks (n=2731) and Whites (n=4158) who from 1994 to 1995 attended high schools that enrolled Black and White students. White female students had higher predicted probabilities of smoking or drinking than did Black female students; the largest differences were in schools with high levels of within-school segregation. Black male students had higher predicted probabilities of high educational aspirations than did White male students in schools with low levels of within-school segregation; this association was attenuated for Black males attending schools with moderate or high levels of within-school segregation. Our results provide evidence that within-school segregation may influence both students' aspirations and their behaviors.

  18. Segregation in handling processes of blended industrial coal

    Energy Technology Data Exchange (ETDEWEB)

    Jones, M.G.; Marjanovic, P.; McGlinchy, D.; McLaren, R. [Glasgow Caledonian University, Glasgow (United Kingdom). Department of Physical Sciences, Centre for Industrial Bulk Solids Handling

    1998-09-01

    A comparison was made between two belt blending methods; using either a compartment hopper or feeder belts. The results indicated that in this case the system with feeder belts gave a more consistent proportioning of materials. Coal when formed into a heap was shown to segregate dependent on size fraction. The level of segregation for each size fraction was quantified using ANOVA statistics. Any measure taken to mitigate this segregation could then be properly assessed. Some aspects of the segregation evident in the heap arose in previous handling steps showing that such effects are transmittable along a process stream. Singles coal when pneumatically conveyed in dilute phase will segregate in the conveying pipeline. Segregation in the direction of travel was minimal in dense phase conveying although the materials tested separated through the depth of the pipe. A full scale experimental programme investigating segregation in both dense and dilute phase is currently underway. 7 refs., 2 figs., 4 tabs.

  19. Rapid mass segregation in small stellar clusters

    Science.gov (United States)

    Spera, Mario; Capuzzo-Dolcetta, Roberto

    2017-12-01

    In this paper we focus our attention on small-to-intermediate N-body systems that are, initially, distributed uniformly in space and dynamically `cool' (virial ratios Q=2T/|Ω| below ˜0.3). In this work, we study the mass segregation that emerges after the initial violent dynamical evolution. At this scope, we ran a set of high precision N-body simulations of isolated clusters by means of HiGPUs, our direct summation N-body code. After the collapse, the system shows a clear mass segregation. This (quick) mass segregation occurs in two phases: the first shows up in clumps originated by sub-fragmentation before the deep overall collapse; this segregation is partly erased during the deep collapse to re-emerge, abruptly, during the second phase, that follows the first bounce of the system. In this second stage, the proper clock to measure the rate of segregation is the dynamical time after virialization, which (for cold and cool systems) may be significantly different from the crossing time evaluated from initial conditions. This result is obtained for isolated clusters composed of stars of two different masses (in the ratio mh/ml=2), at varying their number ratio, and is confirmed also in presence of a massive central object (simulating a black hole of stellar size). Actually, in stellar systems starting their dynamical evolution from cool conditions, the fast mass segregation adds to the following, slow, secular segregation which is collisionally induced. The violent mass segregation is an effect persistent over the whole range of N (128 ≤ N ≤1,024) investigated, and is an interesting feature on the astronomical-observational side, too. The semi-steady state reached after virialization corresponds to a mass segregated distribution function rather than that of equipartition of kinetic energy per unit mass as it should result from violent relaxation.

  20. Radiation-induced segregation in Cu-Au alloys

    International Nuclear Information System (INIS)

    Hashimoto, T.; Rehn, L.E.; Okamoto, P.R.

    1987-01-01

    Radiation-induced segregation in a Cu-lat.% Au alloy was investigated using in-situ Rutherford backscattering spectrometry. Irradiation with 1.8-MeV helium produced nonequilibrium gold atom depletion in the near surface region. The amount of segregation was measured as a function of dose, dose rate, and temperature. Segregation was observed in the temperature range between about 300 and 500 0 C. For a calculated dose rate of 3.9 x 10/sup -5/ dpa/s, the radiation-induced segregation rate peaked near 400 0 C. Theoretical analysis based on the Johnson-Lam model predicted that the amount of segregation would be directly proportional to dose at the early stage of irradiation, would deviate from linearity with a continuously decreasing slope of intermediate doses, and finally approach a constant value after high doses. The analysis also predicted that the segregation rate would vary as the - 1/4th power of the dose rate at constant dose in the low temperature region. These predictions were all verified experimentally. A procedure for extracting relative defect production efficiencies from similar measurements is discussed

  1. Auditory stream segregation using amplitude modulated bandpass noise

    Directory of Open Access Journals (Sweden)

    Yingjiu eNie

    2015-08-01

    Full Text Available The purpose of this study was to investigate the roles of spectral overlap and amplitude modulation (AM rate for stream segregation for noise signals, as well as to test the build-up effect based on these two cues. Segregation ability was evaluated using an objective paradigm with listeners’ attention focused on stream segregation. Stimulus sequences consisted of two interleaved sets of bandpass noise bursts (A and B bursts. The A and B bursts differed in spectrum, AM-rate, or both. The amount of the difference between the two sets of noise bursts was varied. Long and short sequences were studied to investigate the build-up effect for segregation based on spectral and AM-rate differences. Results showed the following: 1. Stream segregation ability increased with greater spectral separation. 2. Larger AM-rate separations were associated with stronger segregation abilities. 3. Spectral separation was found to elicit the build-up effect for the range of spectral differences assessed in the current study. 4. AM-rate separation interacted with spectral separation suggesting an additive effect of spectral separation and AM-rate separation on segregation build-up. The findings suggest that, when normal-hearing listeners direct their attention toward segregation, they are able to segregate auditory streams based on reduced spectral contrast cues that vary by the amount of spectral overlap. Further, regardless of the spectral separation they were able to use AM-rate difference as a secondary/weaker cue. Based on the spectral differences, listeners can segregate auditory streams better as the listening duration is prolonged—i.e. sparse spectral cues elicit build-up segregation; however, AM-rate differences only appear to elicit build-up when in combination with spectral difference cues.

  2. Toxicologic and Analytical Studies with T-2 and Related Trichothecene Mycotoxins

    Science.gov (United States)

    1985-08-20

    damaged myocytes, hypercontraction bands with myofibrillar, lysis or marked distension of sarcoplasmic reticulum with myofibrillar ly Is. * ’was...the increased activity of AST in both groups may suggest toxic or ischemic damage ’to visceral or muscular tissues. In the low dose group, systemic...pig. If there is a sudden change In the respiratory requirements, th? air accessory hose (Figure 3) can be used to rapidly add air to the distensible

  3. Ryanodine receptor 1 and associated pathologies

    OpenAIRE

    Fauré , Julien; Lunardi , Joël; Monnier , Nicole; Marty , Isabelle

    2014-01-01

    In skeletal muscle a rise in the cytosolic calcium concentration is the first trigger able to initiate the contraction of the sarcomere. Intracellular calcium levels are tightly controlled by channels and pumps, and it is not surprising that many inherited skeletal muscle disorders arise from mutations altering the players regulating calcium ions concentration (Betzenhauser et al., 2010). In this chapter, we will focus on the pathologies linked to the sarcoplasmic reticulum calcium channel-Ry...

  4. Ab-initio study of surface segregation in aluminum alloys

    Energy Technology Data Exchange (ETDEWEB)

    Qin, Yifa, E-mail: yfqin10s@imr.ac.cn; Wang, Shaoqing

    2017-03-31

    Highlights: • A thorough study of surface segregation energies of 41 elements in Al is performed. • Segregation energies vary periodically with the atomic numbers of impurities. • 41 elements are classified into 3 groups according to the signs of segregation energies. • The results are validated by the surface/total concentration ratio in Al alloys. - Abstract: We have calculated surface segregation energies of 41 impurities by means of density functional theory calculations. An interesting periodical variation tendency was found for surface segregation energies derived. For the majority of main group elements, segregation energies are negative which means solute elements enrichment at Al surface is energetically more favorable than uniformly dissolution. Half of transition elements possess positive segregation energies and the energies are sensitive to surface crystallographic orientations. A strong correlation is found between the segregation energies at the Al surface and the surface energ of solute elements.

  5. Osteochondritis dissecans (OCD), an endoplasmic reticulum storage disease?

    DEFF Research Database (Denmark)

    Skagen, Peter Storgaard; Horn, T; Kruse, H A

    2011-01-01

    Osteochondritis dissecans (OCD) fragments, cartilage and blood from four patients were used for morphological and molecular analysis. Controls included articular cartilage and blood samples from healthy individuals. Light microscopy and transmission electron microscopy (TEM) showed abnormalities...... in chondrocytes and extracellular matrix of cartilage from OCD patients. Abnormal type II collagen heterofibrils in "bundles" and chondrocytes with abnormal accumulation of matrix proteins in distended rough endoplasmic reticulum were typical findings. Further, Von Kossa staining and TEM showed empty lacunae...... polymorphism was found within the COL2A1 gene for one patient. We suggest that OCD lesions are caused by an alteration in chondrocyte matrix synthesis causing an endoplasmic reticulum storage disease phenotype, which disturbs or abrupts endochondral ossification....

  6. Segregation-mobility feedback for bidisperse shallow granular flows: Towards understanding segregation in geophysical flows

    Science.gov (United States)

    Thornton, A.; Denissen, I.; Weinhart, T.; Van der Vaart, K.

    2017-12-01

    The flow behaviour of shallow granular chute flows for uniform particles is well-described by the hstop-rheology [1]. Geophysical flows, however, are often composed of highly non-uniform particles that differ in particle (size, shape, composition) or contact (friction, dissipation, cohesion) properties. The flow behaviour of such mixtures can be strongly influenced by particle segregation effects. Here, we study the influence of particle size-segregation on the flow behaviour of bidisperse flows using experiments and the discrete particle method. We use periodic DPM to derive hstop-rheology for the bi-dispersed granular shallow layer equations, and study their dependence on the segregation profile. In the periodic box simulations, size-segregation results in an upward coarsening of the size distribution with the largest grains collecting at the top of the flow. In geophysical flows, the fact the flow velocity is greatest at the top couples with the vertical segregation to preferentially transported large particles to the front. The large grains may be overrun, resegregated towards the surface and recirculated before being shouldered aside into lateral levees. Theoretically it has been suggested this process should lead to a breaking size-segregation (BSS) wave located between a large-particle-rich front and a small-particle-rich tail [2,3]. In the BSS wave large particles that have been overrun rise up again to the free-surface while small particles sink to the bed. We present evidence for the existences of the BSS wave. This is achieved through the study of three-dimensional bidisperse granular flows in a moving-bed channel. Our analysis demonstrates a relation between the concentration of small particles in the flow and the amount of basal slip, in which the structure of the BSS wave plays a key role. This leads to a feedback between the mean bulk flow velocity and the process of size-segregation. Ultimately, these findings shed new light on the recirculation of

  7. From particle segregation to the granular clock

    International Nuclear Information System (INIS)

    Lambiotte, R.; Salazar, J.M.; Brenig, L.

    2005-01-01

    Recently several authors studied the segregation of particles for a system composed of mono-dispersed inelastic spheres contained in a box divided by a wall in the middle. The system exhibited a symmetry breaking leading to an overpopulation of particles in one side of the box. Here we study the segregation of a mixture of particles composed of inelastic hard spheres and fluidized by a vibrating wall. Our numerical simulations show a rich phenomenology: horizontal segregation and periodic behavior. We also propose an empirical system of ODEs representing the proportion of each type of particles and the segregation flux of particles. These equations reproduce the major features observed by the simulations

  8. From particle segregation to the granular clock

    Energy Technology Data Exchange (ETDEWEB)

    Lambiotte, R. [Physique Statistique, Plasmas et Optique Non-lineaire, Universite Libre de Bruxelles, Campus Plaine, Boulevard du Triomphe, Code Postal 231, 1050 Brussels (Belgium)]. E-mail: rlambiot@ulb.ac.be; Salazar, J.M. [Universite De Bougogne-LRRS UMR-5613 CNRS, Faculte des Sciences Mirande, 9 Av. Alain Savary, 21078 Dijon Cedex (France)]. E-mail: jmarcos@u-bourgogne.fr; Brenig, L. [Physique Statistique, Plasmas et Optique Non-lineaire, Universite Libre de Bruxelles, Campus Plaine, Boulevard du Triomphe, Code Postal 231, 1050 Brussels (Belgium)]. E-mail: lbrenig@ulb.ac.be

    2005-08-01

    Recently several authors studied the segregation of particles for a system composed of mono-dispersed inelastic spheres contained in a box divided by a wall in the middle. The system exhibited a symmetry breaking leading to an overpopulation of particles in one side of the box. Here we study the segregation of a mixture of particles composed of inelastic hard spheres and fluidized by a vibrating wall. Our numerical simulations show a rich phenomenology: horizontal segregation and periodic behavior. We also propose an empirical system of ODEs representing the proportion of each type of particles and the segregation flux of particles. These equations reproduce the major features observed by the simulations.

  9. Acyl-CoA-binding protein (ACBP) localizes to the endoplasmic reticulum and Golgi in a ligand-dependent manner in mammalian cells

    DEFF Research Database (Denmark)

    Hansen, Jesper S; Færgeman, Nils J; Kragelund, Birthe B

    2008-01-01

    showed that ACBP targeted to the ER (endoplasmic reticulum) and Golgi in a ligand-binding-dependent manner. A variant Y28F/K32A-FACI-50, which is unable to bind acyl-CoA, did no longer show association with the ER and became segregated from the Golgi, as analysed by intensity correlation calculations....... Depletion of fatty acids from cells by addition of FAFBSA (fatty-acid-free BSA) significantly decreased FACI-50 association with the Golgi, whereas fatty acid overloading increased Golgi association, strongly supporting that ACBP associates with the Golgi in a ligand-dependent manner. FRAP (fluorescence...... recovery after photobleaching) showed that the fatty-acid-induced targeting of FACI-50 to the Golgi resulted in a 5-fold reduction in FACI-50 mobility. We suggest that ACBP is targeted to the ER and Golgi in a ligand-binding-dependent manner in living cells and propose that ACBP may be involved...

  10. Asymmetric strand segregation: epigenetic costs of genetic fidelity?

    Directory of Open Access Journals (Sweden)

    Diane P Genereux

    2009-06-01

    Full Text Available Asymmetric strand segregation has been proposed as a mechanism to minimize effective mutation rates in epithelial tissues. Under asymmetric strand segregation, the double-stranded molecule that contains the oldest DNA strand is preferentially targeted to the somatic stem cell after each round of DNA replication. This oldest DNA strand is expected to have fewer errors than younger strands because some of the errors that arise on daughter strands during their synthesis fail to be repaired. Empirical findings suggest the possibility of asymmetric strand segregation in a subset of mammalian cell lineages, indicating that it may indeed function to increase genetic fidelity. However, the implications of asymmetric strand segregation for the fidelity of epigenetic information remain unexplored. Here, I explore the impact of strand-segregation dynamics on epigenetic fidelity using a mathematical-modelling approach that draws on the known molecular mechanisms of DNA methylation and existing rate estimates from empirical methylation data. I find that, for a wide range of starting methylation densities, asymmetric -- but not symmetric -- strand segregation leads to systematic increases in methylation levels if parent strands are subject to de novo methylation events. I found that epigenetic fidelity can be compromised when enhanced genetic fidelity is achieved through asymmetric strand segregation. Strand segregation dynamics could thus explain the increased DNA methylation densities that are observed in structured cellular populations during aging and in disease.

  11. Housing Systems and Ethnic Spatial Segregation

    DEFF Research Database (Denmark)

    Andersen, Hans Skifter; Andersson, Roger; Wessel, Terje

    Residential spatial segregation is related to housing markets and housing policies. In this paper, ethnic segregation is compared across four Nordic capitals and explanations for the differences are examined by comparing the housing markets and housing policies of the countries. The housing markets...

  12. Study on segregation of aluminium-uranium alloys

    International Nuclear Information System (INIS)

    Lima, Rui Marques de

    1979-01-01

    The relations between alloy solidification and solute segregation were considered. The solidification structure and the solute redistribution during the solidification of alloys with dendritic micro morphology were studied. The macro and micro segregation theories were reviewed. The mechanisms that could change the solidification structure were taken into account in the context of more homogeneous alloy production. Aluminum alloys solidification structures and segregation were studied experimentally in the 13 to 45% uranium range, usually considering solidification in static molds. The uranium alloys with up to 20% uranium were studied both for solidification in ingot molds and for controlled directional solidification. It was verified that these alloy compositions had structures similar to those of hipoeutectic alloys, showing an a phase with dendritic morphology and inter dendritic eutectic. For the alloys with more than 25% uranium, it was observed the formation of UAl 3 and UAl 4 phases with dendritic morphology. The dendritic UAl 3 , phase morphology was affected both by the solute concentration in the alloy and by the growth rate. The dendritic UAl 3 phase non-singular aspect could be destroyed with decrease of the alloy solute concentration. In the alloys obtained with higher cooling rates it was found a tendency for the formation of substantial quantities of equi axial crystals of the solute enriched phases in the central regions of the ingot upper half. In the more external regions it was observed dendritic growth of these phases, for alloy compositions with over 25% uranium. An adequate reduction in the cooling rate changed the solidification structure form and distribution, as well as the segregation type and intensity. The uranium content in the solidified macro structures is presented as a function of: cooling rate, superheating, mold size, mold form and its temperature, number of remelting and time for the melt homogenization and agitation. It was

  13. Granular Segregation by an Oscillating Ratchet Mechanism

    International Nuclear Information System (INIS)

    Igarashi, A.; Horiuchi, Ch.

    2004-01-01

    We report on a method to segregate granular mixtures which consist of two kinds of particles by an oscillating ''ratchet'' mechanism. The segregation system has an asymmetrical sawtooth-shaped base which is vertically oscillating. Such a ratchet base produces a directional current of particles owing to its transport property. It is a counterintuitive and interesting phenomenon that a vertically vibrated base transports particles horizontally. This system is studied with numerical simulations, and it is found that we can apply such a system to segregation of mixtures of particles with different properties (radius or mass). Furthermore, we find out that an appropriate inclination of the ratchet-base makes the quality of segregation high. (author)

  14. PICH promotes mitotic chromosome segregation

    DEFF Research Database (Denmark)

    Nielsen, Christian Thomas Friberg; Hickson, Ian D

    2016-01-01

    PICH is an SNF2-family DNA translocase that appears to play a role specifically in mitosis. Characterization of PICH in human cells led to the initial discovery of "ultra-fine DNA bridges" (UFBs) that connect the 2 segregating DNA masses in the anaphase of mitosis. These bridge structures, which...... further the role of PICH in the timely segregation of the rDNA locus....

  15. Endoplasmic Reticulum Stress and Obesity.

    Science.gov (United States)

    Yilmaz, Erkan

    2017-01-01

    In recent years, the world has seen an alarming increase in obesity and closely associated with insulin resistance which is a state of low-grade inflammation, the latter characterized by elevated levels of proinflammatory cytokines in blood and tissues. A shift in energy balance alters systemic metabolic regulation and the important role that chronic inflammation, endoplasmic reticulum (ER) dysfunction, and activation of the unfolded protein response (UPR) play in this process.Why obesity is so closely associated with insulin resistance and inflammation is not understood well. This suggests that there are probably other causes for obesity-related insulin resistance and inflammation. One of these appears to be endoplasmic reticulum (ER) stress.The ER is a vast membranous network responsible for the trafficking of a wide range of proteins and plays a central role in integrating multiple metabolic signals critical in cellular homeostasis. Conditions that may trigger unfolded protein response activation include increased protein synthesis, the presence of mutant or misfolded proteins, inhibition of protein glycosylation, imbalance of ER calcium levels, glucose and energy deprivation, hypoxia, pathogens or pathogen-associated components and toxins. Thus, characterizing the mechanisms contributing to obesity and identifying potential targets for its prevention and treatment will have a great impact on the control of associated conditions, particularly T2D.

  16. Analysis of Minor Component Segregation in Ternary Powder Mixtures

    Directory of Open Access Journals (Sweden)

    Asachi Maryam

    2017-01-01

    Full Text Available In many powder handling operations, inhomogeneity in powder mixtures caused by segregation could have significant adverse impact on the quality as well as economics of the production. Segregation of a minor component of a highly active substance could have serious deleterious effects, an example is the segregation of enzyme granules in detergent powders. In this study, the effects of particle properties and bulk cohesion on the segregation tendency of minor component are analysed. The minor component is made sticky while not adversely affecting the flowability of samples. The segregation extent is evaluated using image processing of the photographic records taken from the front face of the heap after the pouring process. The optimum average sieve cut size of components for which segregation could be reduced is reported. It is also shown that the extent of segregation is significantly reduced by applying a thin layer of liquid to the surfaces of minor component, promoting an ordered mixture.

  17. Stochastic correlative firing for figure-ground segregation.

    Science.gov (United States)

    Chen, Zhe

    2005-03-01

    Segregation of sensory inputs into separate objects is a central aspect of perception and arises in all sensory modalities. The figure-ground segregation problem requires identifying an object of interest in a complex scene, in many cases given binaural auditory or binocular visual observations. The computations required for visual and auditory figure-ground segregation share many common features and can be cast within a unified framework. Sensory perception can be viewed as a problem of optimizing information transmission. Here we suggest a stochastic correlative firing mechanism and an associative learning rule for figure-ground segregation in several classic sensory perception tasks, including the cocktail party problem in binaural hearing, binocular fusion of stereo images, and Gestalt grouping in motion perception.

  18. Segregation in quasi-two-dimensional granular systems

    International Nuclear Information System (INIS)

    Rivas, Nicolas; Cordero, Patricio; Soto, Rodrigo; Risso, Dino

    2011-01-01

    Segregation for two granular species is studied numerically in a vertically vibrated quasi-two-dimensional (quasi-2D) box. The height of the box is smaller than two particle diameters so that particles are limited to a submonolayer. Two cases are considered: grains that differ in their density but have equal size, and grains that have equal density but different diameters, while keeping the quasi-2D condition. It is observed that in both cases, for vibration frequencies beyond a certain threshold-which depends on the density or diameter ratios-segregation takes place in the lateral directions. In the quasi-2D geometry, gravity does not play a direct role in the in-plane dynamics and gravity does not point to the segregation directions; hence, several known segregation mechanisms that rely on gravity are discarded. The segregation we observe is dominated by a lack of equipartition between the two species; the light particles exert a larger pressure than the heavier ones, inducing the latter to form clusters. This energy difference in the horizontal direction is due to the existence of a fixed point characterized by vertical motion and hence vanishing horizontal energy. Heavier and bigger grains are more rapidly attracted to the fixed point and the perturbations are less efficient in taking them off the fixed point when compared to the lighter grains. As a consequence, heavier and bigger grains have less horizontal agitation than lighter ones. Although limited by finite size effects, the simulations suggest that the two cases we consider differ in the transition character: one is continuous and the other is discontinuous. In the cases where grains differ in mass on varying the control parameter, partial segregation is first observed, presenting many clusters of heavier particles. Eventually, a global cluster is formed with impurities; namely lighter particles are present inside. The transition looks continuous when characterized by several segregation order

  19. Sound segregation via embedded repetition is robust to inattention.

    Science.gov (United States)

    Masutomi, Keiko; Barascud, Nicolas; Kashino, Makio; McDermott, Josh H; Chait, Maria

    2016-03-01

    The segregation of sound sources from the mixture of sounds that enters the ear is a core capacity of human hearing, but the extent to which this process is dependent on attention remains unclear. This study investigated the effect of attention on the ability to segregate sounds via repetition. We utilized a dual task design in which stimuli to be segregated were presented along with stimuli for a "decoy" task that required continuous monitoring. The task to assess segregation presented a target sound 10 times in a row, each time concurrent with a different distractor sound. McDermott, Wrobleski, and Oxenham (2011) demonstrated that repetition causes the target sound to be segregated from the distractors. Segregation was queried by asking listeners whether a subsequent probe sound was identical to the target. A control task presented similar stimuli but probed discrimination without engaging segregation processes. We present results from 3 different decoy tasks: a visual multiple object tracking task, a rapid serial visual presentation (RSVP) digit encoding task, and a demanding auditory monitoring task. Load was manipulated by using high- and low-demand versions of each decoy task. The data provide converging evidence of a small effect of attention that is nonspecific, in that it affected the segregation and control tasks to a similar extent. In all cases, segregation performance remained high despite the presence of a concurrent, objectively demanding decoy task. The results suggest that repetition-based segregation is robust to inattention. (c) 2016 APA, all rights reserved).

  20. Residential Segregation in Texas in 1980.

    Science.gov (United States)

    Hwang, Sean-Shong; Murdock, Steve H.

    1982-01-01

    Between 1970 and 1980 racial and ethnic segregation for major Texas cities declined for all groups, but declines were small between Anglo and Spanish groups. Segregation is unaffected by variation in size of city, percent of population that is Spanish or Black, or central city status. (Author/AM)

  1. Sex Segregation in Undergraduate Engineering Majors

    Science.gov (United States)

    Litzler, Elizabeth

    2010-01-01

    Gender inequality in engineering persists in spite of women reaching parity in college enrollments and degrees granted. To date, no analyses of educational sex segregation have comprehensively examined segregation within one discipline. To move beyond traditional methods of studying the long-standing stratification by field of study in higher…

  2. Losing Ground: School Segregation in Massachuestts

    Science.gov (United States)

    Ayscue, Jennifer B.; Greenberg, Alyssa

    2013-01-01

    Though once a leader in school integration, Massachusetts has regressed over the last two decades as its students of color have experienced intensifying school segregation. This report investigates trends in school segregation in Massachusetts by examining concentration, exposure, and evenness measures by both race and class. First, the report…

  3. Administrative Segregation for Mentally Ill Inmates

    Science.gov (United States)

    O'Keefe, Maureen L.

    2007-01-01

    Largely the result of prison officials needing to safely and efficiently manage a volatile inmate population, administrative segregation or supermax facilities are criticized as violating basic human needs, particularly for mentally ill inmates. The present study compared Colorado offenders with mental illness (OMIs) to nonOMIs in segregated and…

  4. Interface segregation behavior in thermal aged austenitic precipitation strengthened stainless steel

    Energy Technology Data Exchange (ETDEWEB)

    Li, Hui [Key Laboratory for Microstructures, Shanghai University, Shanghai 200444 (China); Technical Department, Jiuli Hi-Tech Metals Co., Ltd., Huzhou 313008 (China); Song, Hui [Key Laboratory for Microstructures, Shanghai University, Shanghai 200444 (China); Liu, Wenqing, E-mail: wqliu@staff.shu.edu.cn [Key Laboratory for Microstructures, Shanghai University, Shanghai 200444 (China); Institute of Materials, Shanghai University, Shanghai 200072 (China); Xia, Shuang; Zhou, Bangxin [Institute of Materials, Shanghai University, Shanghai 200072 (China); Su, Cheng; Ding, Wenyan [Technical Department, Jiuli Hi-Tech Metals Co., Ltd., Huzhou 313008 (China)

    2015-12-15

    The segregation of various elements at grain boundaries, precipitate/matrix interfaces were analyzed using atom probe tomography in an austenitic precipitation strengthened stainless steel aged at 750 °C for different time. Segregation of P, B and C at all types of interfaces in all the specimens were observed. However, Si segregated at all types of interfaces only in the specimen aged for 16 h. Enrichment of Ti at grain boundaries was evident in the specimen aged for 16 h, while Ti did not segregate at other interfaces. Mo varied considerably among interface types, e.g. from segregated at grain boundaries in the specimens after all the aging time to never segregate at γ′/γ phase interfaces. Cr co-segregated with C at grain boundaries, although carbides still did not nucleate at grain boundaries yet. Despite segregation tendency variations in different interface types, the segregation tendency evolution variation of different elements depending aging time were analyzed among all types of interfaces. Based on the experimental results, the enrichment factors, Gibbs interface excess and segregation free energies of segregated elements were calculated and discussed. - Highlights: • Solute atoms segregated at interfaces were analyzed in an austenitic stainless steel. • The comparison of segregation in different interfaces was studied by APT. • The evolution of interface segregation during aging treatment was discussed.

  5. Endoplasmic reticulum stress in wake-active neurons progresses with aging.

    Science.gov (United States)

    Naidoo, Nirinjini; Zhu, Jingxu; Zhu, Yan; Fenik, Polina; Lian, Jie; Galante, Ray; Veasey, Sigrid

    2011-08-01

    Fragmentation of wakefulness and sleep are expected outcomes of advanced aging. We hypothesize that wake neurons develop endoplasmic reticulum dyshomeostasis with aging, in parallel with impaired wakefulness. In this series of experiments, we sought to more fully characterize age-related changes in wakefulness and then, in relevant wake neuronal populations, explore functionality and endoplasmic reticulum homeostasis. We report that old mice show greater sleep/wake transitions in the active period with markedly shortened wake periods, shortened latencies to sleep, and less wake time in the subjective day in response to a novel social encounter. Consistent with sleep/wake instability and reduced social encounter wakefulness, orexinergic and noradrenergic wake neurons in aged mice show reduced c-fos response to wakefulness and endoplasmic reticulum dyshomeostasis with increased nuclear translocation of CHOP and GADD34. We have identified an age-related unfolded protein response injury to and dysfunction of wake neurons. It is anticipated that these changes contribute to sleep/wake fragmentation and cognitive impairment in aging. © 2011 The Authors. Aging Cell © 2011 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland.

  6. Gender Segregation in Nursery School: Predictors and Outcomes.

    Science.gov (United States)

    Maccoby, Eleanor E.; Jacklin, Carol Nagy

    Sex segregation is a powerful phenomenon in childhood. It occurs universally whenever children have a choice of playmates and is found in sub-human primates too. Adults are not directly responsible for sex segregation. Data do not support the hypothesis that the most ladylike girls and the most rough and active boys first form the segregated play…

  7. Applied thermodynamics: Grain boundary segregation

    Czech Academy of Sciences Publication Activity Database

    Lejček, Pavel; Zheng, L.; Hofmann, S.; Šob, Mojmír

    2014-01-01

    Roč. 16, č. 3 (2014), s. 1462-1484 ISSN 1099-4300 R&D Projects: GA ČR(CZ) GAP108/12/0311; GA ČR GAP108/12/0144; GA MŠk(CZ) ED1.1.00/02.0068 Institutional support: RVO:68378271 ; RVO:68081723 Keywords : interfacial segregation * Gibbs energy of segregation * enthalpy * entropy * volume * grain boundaries * iron Subject RIV: BM - Solid Matter Physics ; Magnetism Impact factor: 1.502, year: 2014

  8. Inhibition of NAPDH Oxidase 2 (NOX2 Prevents Oxidative Stress and Mitochondrial Abnormalities Caused by Saturated Fat in Cardiomyocytes.

    Directory of Open Access Journals (Sweden)

    Leroy C Joseph

    Full Text Available Obesity and high saturated fat intake increase the risk of heart failure and arrhythmias. The molecular mechanisms are poorly understood. We hypothesized that physiologic levels of saturated fat could increase mitochondrial reactive oxygen species (ROS in cardiomyocytes, leading to abnormalities of calcium homeostasis and mitochondrial function. We investigated the effect of saturated fat on mitochondrial function and calcium homeostasis in isolated ventricular myocytes. The saturated fatty acid palmitate causes a decrease in mitochondrial respiration in cardiomyocytes. Palmitate, but not the monounsaturated fatty acid oleate, causes an increase in both total cellular ROS and mitochondrial ROS. Palmitate depolarizes the mitochondrial inner membrane and causes mitochondrial calcium overload by increasing sarcoplasmic reticulum calcium leak. Inhibitors of PKC or NOX2 prevent mitochondrial dysfunction and the increase in ROS, demonstrating that PKC-NOX2 activation is also required for amplification of palmitate induced-ROS. Cardiomyocytes from mice with genetic deletion of NOX2 do not have palmitate-induced ROS or mitochondrial dysfunction. We conclude that palmitate induces mitochondrial ROS that is amplified by NOX2, causing greater mitochondrial ROS generation and partial depolarization of the mitochondrial inner membrane. The abnormal sarcoplasmic reticulum calcium leak caused by palmitate could promote arrhythmia and heart failure. NOX2 inhibition is a potential therapy for heart disease caused by diabetes or obesity.

  9. Altered elementary calcium release events and enhanced calcium release by thymol in rat skeletal muscle.

    Science.gov (United States)

    Szentesi, Péter; Szappanos, Henrietta; Szegedi, Csaba; Gönczi, Monika; Jona, István; Cseri, Julianna; Kovács, László; Csernoch, László

    2004-03-01

    The effects of thymol on steps of excitation-contraction coupling were studied on fast-twitch muscles of rodents. Thymol was found to increase the depolarization-induced release of calcium from the sarcoplasmic reticulum, which could not be attributed to a decreased calcium-dependent inactivation of calcium release channels/ryanodine receptors or altered intramembrane charge movement, but rather to a more efficient coupling of depolarization to channel opening. Thymol increased ryanodine binding to heavy sarcoplasmic reticulum vesicles, with a half-activating concentration of 144 micro M and a Hill coefficient of 1.89, and the open probability of the isolated and reconstituted ryanodine receptors, from 0.09 +/- 0.03 to 0.22 +/- 0.04 at 30 micro M. At higher concentrations the drug induced long-lasting open events on a full conducting state. Elementary calcium release events imaged using laser scanning confocal microscopy in the line-scan mode were reduced in size, 0.92 +/- 0.01 vs. 0.70 +/- 0.01, but increased in duration, 56 +/- 1 vs. 79 +/- 1 ms, by 30 micro M thymol, with an increase in the relative proportion of lone embers. Higher concentrations favored long events, resembling embers in control, with duration often exceeding 500 ms. These findings provide direct experimental evidence that the opening of a single release channel will generate an ember, rather than a spark, in mammalian skeletal muscle.

  10. (-)-Epicatechin-induced relaxation of isolated human saphenous vein: Roles of K+ and Ca2+ channels.

    Science.gov (United States)

    Marinko, Marija; Jankovic, Goran; Nenezic, Dragoslav; Milojevic, Predrag; Stojanovic, Ivan; Kanjuh, Vladimir; Novakovic, Aleksandra

    2018-02-01

    In this study, we aimed to investigate relaxant effect of flavanol (-)-epicatechin on the isolated human saphenous vein (HSV), as a part of its cardioprotective action, and to define the mechanisms underlying this vasorelaxation. (-)-Epicatechin induced a concentration-dependent relaxation of HSV pre-contracted by phenylephrine. Among K + channel blockers, 4-aminopyridine, margatoxin, and iberiotoxin significantly inhibited relaxation of HSV, while glibenclamide considerably reduced effects of the high concentrations of (-)-epicatechin. Additionally, (-)-epicatechin relaxed contraction induced by 80 mM K + , whereas in the presence of nifedipine produced partial relaxation of HSV rings pre-contracted by phenylephrine. In Ca 2+ -free solution, (-)-epicatechin relaxed contraction induced by phenylephrine, but had no effect on contraction induced by caffeine. A sarcoplasmic reticulum Ca 2+ -ATPase inhibitor, thapsigargin, significantly reduced relaxation of HSV produced by (-)-epicatechin. These results demonstrate that (-)-epicatechin produces endothelium-independent relaxation of isolated HSV rings. Vasorelaxation to (-)-epicatechin probably involves activation of 4-aminopyridine- and margatoxin-sensitive K V channels, BK Ca channels, and at least partly, K ATP channels. In addition, not only the inhibition of extracellular Ca 2+ influx, but regulation of the intracellular Ca 2+ release, via inositol-trisphosphate receptors and reuptake into sarcoplasmic reticulum, via stimulation of Ca 2+ -ATPase, as well, most likely participate in (-)-epicatechin-induced relaxation of HSV. Copyright © 2017 John Wiley & Sons, Ltd.

  11. The endoplasmic reticulum stress response in disease ...

    African Journals Online (AJOL)

    Rafael Vincent M. Manalo

    2017-07-12

    Jul 12, 2017 ... Review. The endoplasmic reticulum stress response in disease pathogenesis and pathophysiology .... This is an open access article under the CC BY-NC-ND license ... chain binding protein (BIP); however, ER stress permits the release, .... drugs designed to alleviate it often cause more harm long-term.

  12. Interface segregation behavior in thermal aged austenitic precipitation strengthened stainless steel.

    Science.gov (United States)

    Li, Hui; Song, Hui; Liu, Wenqing; Xia, Shuang; Zhou, Bangxin; Su, Cheng; Ding, Wenyan

    2015-12-01

    The segregation of various elements at grain boundaries, precipitate/matrix interfaces were analyzed using atom probe tomography in an austenitic precipitation strengthened stainless steel aged at 750 °C for different time. Segregation of P, B and C at all types of interfaces in all the specimens were observed. However, Si segregated at all types of interfaces only in the specimen aged for 16 h. Enrichment of Ti at grain boundaries was evident in the specimen aged for 16 h, while Ti did not segregate at other interfaces. Mo varied considerably among interface types, e.g. from segregated at grain boundaries in the specimens after all the aging time to never segregate at γ'/γ phase interfaces. Cr co-segregated with C at grain boundaries, although carbides still did not nucleate at grain boundaries yet. Despite segregation tendency variations in different interface types, the segregation tendency evolution variation of different elements depending aging time were analyzed among all types of interfaces. Based on the experimental results, the enrichment factors, Gibbs interface excess and segregation free energies of segregated elements were calculated and discussed. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Element segregation behavior of aluminum-copper alloy ZL205A

    Directory of Open Access Journals (Sweden)

    Fan Li

    2014-11-01

    Full Text Available In aluminum-copper alloy, the segregation has a severe bad effect on the alloying degree, strength and corrosion resistance. A deeper understanding of element segregation behavior will have a great significance on the prevention of segregation. In the study, the element segregation behavior of ZL205A aluminum-copper alloy was investigated by examining isothermally solidified samples using scanning electron microscopy and energy dispersive spectroscopy. The calculated results of segregation coefficients show that Cu and Mn are negative segregation elements; while Ti, V and Zr are positive segregation elements. The sequence of element segregation degree from the greatest to the least in ZL205A alloy is Cu, Mn, V, Ti, Zr and Al. The density of residual liquid is expected to increase with a decrease in the quenching temperature ranging from 630 ºC to 550 ºC. The calculated results confirm that the quenching temperature has an insignificant effect on the liquid density; and the variation of density is mainly due to element segregation. Consequently, segregations of Al, Cu and Mn lead to an increase in density, but Ti, V and Zr present the opposite effect. The contribution of each element to the variation of the liquid density was analyzed. The sequence of contributions of alloying elements to the variation of total liquid density is Cu﹥Al﹥Mn﹥V﹥Ti﹥Zr.

  14. Habitat segregation in fish assemblages

    OpenAIRE

    Ibbotson, A.T.

    1990-01-01

    The segregation of habitats of fish assemblages found in the chalk streams and rivers within the Wessex, South West and Southern Water Authority boundaries in southern England have been examined. Habitat segregation is the most frequent type of resource partitioning in natural communities. The habitat of individual fish species will be defined in order to determine the following: (1) the requirements of each species in terms of depth, current velocity, substrate, cover etc.; (2) identify the ...

  15. Segregation in a Galton Board

    International Nuclear Information System (INIS)

    Benito, J G; Vidales, A M; Ippolito, I

    2009-01-01

    This work deals with a numerical study of the problem of separation of particles with different elastic properties. The separation procedure uses a Galton Board which consist in a bidimensional system of obstacles arranged in a triangular lattice. Disks of equal diameters but different elastic properties are launched from the top of the device. The Galton Board is commonly used for mixing particles, but here, we intend to find special conditions under which one can use it as a segregating device. We introduce a mixture of particles and generate, through simulations, different conditions to favor the segregation process based on the different elastic coefficients of the particles. We inspect which is the best configuration of size, density of obstacles and wall separation to favor the separations of particles. Our results prove that the Galton Board can be used as a segregation device under certain conditions.

  16. Micro and Macro Segregation in Alloys Solidifying with Equiaxed Morphology

    Science.gov (United States)

    Stefanescu, Doru M.; Curreri, Peter A.; Leon-Torres, Jose; Sen, Subhayu

    1996-01-01

    To understand macro segregation formation in Al-Cu alloys, experiments were run under terrestrial gravity (1g) and under low gravity during parabolic flights (10(exp -2) g). Alloys of two different compositions (2% and 5% Cu) were solidified at two different cooling rates. Systematic microscopic and SEM observations produced microstructural and segregation maps for all samples. These maps may be used as benchmark experiments for validation of microstructure evolution and segregation models. As expected, the macro segregation maps are very complex. When segregation was measured along the central axis of the sample, the highest macro segregation for samples solidified at 1g was obtained for the lowest cooling rate. This behavior is attributed to the longer time available for natural convection and shrinkage flow to affect solute redistribution. In samples solidified under low-g, the highest macro-segregation was obtained at the highest cooling rate. In general, low-gravity solidification resulted in less segregation. To explain the experimental findings, an analytical (Flemings-Nereo) and a numerical model were used. For the numerical model, the continuum formulation was employed to describe the macroscopic transports of mass, energy, and momentum, associated with the microscopic transport phenomena, for a two-phase system. The model proposed considers that liquid flow is driven by thermal and solutal buoyancy, and by solidification shrinkage. The Flemings-Nereo model explains well macro segregation in the initial stages of low-gravity segregation. The numerical model can describe the complex macro segregation pattern and the differences between low- and high-gravity solidification.

  17. Sex segregation in undergraduate engineering majors

    Science.gov (United States)

    Litzler, Elizabeth

    Gender inequality in engineering persists in spite of women reaching parity in college enrollments and degrees granted. To date, no analyses of educational sex segregation have comprehensively examined segregation within one discipline. To move beyond traditional methods of studying the long-standing stratification by field of study in higher education, I explore gender stratification within one field: engineering. This dissertation investigates why some engineering disciplines have a greater representation of women than other engineering disciplines. I assess the individual and institutional factors and conditions associated with women's representation in certain engineering departments and compare the mechanisms affecting women's and men's choice of majors. I use national data from the Engineering Workforce Commission, survey data from 21 schools in the Project to Assess Climate in Engineering study, and Carnegie Foundation classification information to study sex segregation in engineering majors from multiple perspectives: the individual, major, institution, and country. I utilize correlations, t-tests, cross-tabulations, log-linear modeling, multilevel logistic regression and weighted least squares regression to test the relative utility of alternative explanations for women's disproportionate representation across engineering majors. As a whole, the analyses illustrate the importance of context and environment for women's representation in engineering majors. Hypotheses regarding hostile climate and discrimination find wide support across different analyses, suggesting that women's under-representation in certain engineering majors is not a question of choice or ability. However, individual level factors such as having engineering coursework prior to college show an especially strong association with student choice of major. Overall, the analyses indicate that institutions matter, albeit less for women, and women's under-representation in engineering is not

  18. 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

  19. 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

  20. Is the Ca2+-ATPase from sarcoplasmic reticulum also a heat pump?

    Science.gov (United States)

    Kjelstrup, Signe; de Meis, Leopoldo; Bedeaux, Dick; Simon, Jean-Marc

    2008-11-01

    We calculate, using the first law of thermodynamics, the membrane heat fluxes during active transport of Ca(2+) in the Ca(2+)-ATPase in leaky and intact vesicles, during ATP hydrolysis or synthesis conditions. The results show that the vesicle interior may cool down during hydrolysis and Ca(2+)-uptake, and heat up during ATP synthesis and Ca(2+)-efflux. The heat flux varies with the SERCA isoform. Electroneutral processes and rapid equilibration of water were assumed. The results are consistent with the second law of thermodynamics for the overall processes. The expression for the heat flux and experimental data, show that important contributions come from the enthalpy of hydrolysis for the medium in question, and from proton transport between the vesicle interior and exterior. The analysis give quantitative support to earlier proposals that certain, but not all, Ca(2+)-ATPases, not only act as Ca(2+)-pumps, but also as heat pumps. It can thus help explain why SERCA 1 type enzymes dominate in tissues where thermal regulation is important, while SERCA 2 type enzymes, with their lower activity and better ability to use the energy from the reaction to pump ions, dominate in tissues where this is not an issue.

  1. Direct measurement of newly synthesized ATP dissociation kinetics in sarcoplasmic reticulum ATPase

    International Nuclear Information System (INIS)

    Teruel-Puche, J.; Kurzmack, M.; Inesi, G.

    1987-01-01

    Incubation of SR vesicles with Ca 2+ and ( 32 P)acetylphosphate, yields steady state levels of ( 32 P)phosphorylated enzyme (ATPase) intermediate and high concentrations of Ca 2+ in the lumen of the vesicles. At this time, addition of ADP (and EGTA to lower the Ca 2+ concentration in the medium outside the vesicles) results in single cycle formation of (γ- 32 P)ATP by transfer of ( 32 P)phosphate from the enzyme intermediate to ADP. The phosphoenzyme decay and ATP formation exhibit a fast component within the first 20 msec following addition of ADP, and a slower component reaching an asymptote in approximately 100 msec. They have now measured by a rapid filtration method the fraction of newly synthesized ATP which is bound to the enzyme, as opposed to the fraction dissociated into the medium. They find that nearly all the ATP formed during the initial burst is still bound to the enzyme within the initial 20 msec of reaction. Dissociation of newly synthesized ATP occurs then with approximately 13 sec -1 rate constant, permitting reequilibration of the system and further formation of ATP. The rate limiting effect of ATP dissociation and other partial reactions on the slow component of single cycle ATP synthesis is evaluated by appropriate kinetic simulations

  2. Gender Segregation in the Spanish Labor Market: An Alternative Approach

    Science.gov (United States)

    del Rio, Coral; Alonso-Villar, Olga

    2010-01-01

    The aim of this paper is to study occupational segregation by gender in Spain, which is a country where occupational segregation explains a large part of the gender wage gap. As opposed to previous studies, this paper measures not only overall segregation, but also the segregation of several population subgroups. For this purpose, this paper uses…

  3. Calcium and Mitosis

    Science.gov (United States)

    Hepler, P.

    1983-01-01

    Although the mechanism of calcium regulation is not understood, there is evidence that calcium plays a role in mitosis. Experiments conducted show that: (1) the spindle apparatus contains a highly developed membrane system that has many characteristics of sarcoplasmic reticulum of muscle; (2) this membrane system contains calcium; and (3) there are ionic fluxes occurring during mitosis which can be seen by a variety of fluorescence probes. Whether the process of mitosis can be modulated by experimentally modulating calcium is discussed.

  4. Evidence that the effects of phospholipids on the activity of the Ca(2+)-ATPase do not involve aggregation.

    OpenAIRE

    Starling, A P; East, J M; Lee, A G

    1995-01-01

    The Ca(2+)-ATPase of skeletal-muscle sarcoplasmic reticulum, solubilized in monomeric from in C12E8, has been reconstituted by dialysis into sealed vesicles of dioleoyl phosphatidylcholine [di(C18:1)PC], dimyristoleoyl phosphatidylcholine [di(C14:1)PC], dinervonyl phosphatidylcholine [di(C24:1)PC] or dipalmitoyl phosphatidylcholine [di(C16:0)PC] in the gel phase, at a phospholipid/ATPase molar ratio of 10,000: 1. Cross-linking experiments show that ATPase molecules are present in these recons...

  5. Radiation induced phosphorus segregation in austenitic and ferritic alloys

    International Nuclear Information System (INIS)

    Brimhall, J.L.; Baer, D.R.; Jones, R.H.

    1984-01-01

    The radiation induced surface segregation (RIS) of phosphorus in stainless steel attained a maximum at a dose of 0.8 dpa then decreased continually with dose. This decrease in the surface segregation of phosphorus at high dose levels has been attributed to removal of the phosphorus layer by ion sputtering. Phosphorus is not replenished since essentially all of the phosphorus within the irradiation zone has been segregated to the surface. Sputter removal can explain the previously reported absence of phosphorus segregation in ferritic alloys irradiated at high dosessup(1,2) (>1 dpa) since irradiation of ferritic alloys to low doses has shown measurable RIS. This sputtering phenomenon places an inherent limitation to the heavy ion irradiation technique for the study of surface segregation of impurity elements. The magnitude of the segregation in ferritics is still much less than in stainless steel which can be related to the low damage accumulation in these alloys. (orig.)

  6. Improvement in dry active waste segregation and processing

    International Nuclear Information System (INIS)

    Hillmer, T.P.; Anderson, K.D.; Dahlen, D.E.

    1989-01-01

    At the Palo Verde Nuclear Generating Station (PVNGS) the majority of dry active waste (DAW) volume reduction activities are performed in the site's new DAW processing and storage facility. This facility houses an interim storage area for a five year volume of compacted DAW, a shredder/compactor, and a DAW segregation area. The DAW segregation program locates and separates non-radioactive and reusable materials from DAW generated at the three unit PVNGS site. This program has saved more than 24,000 cubic feet of burial space and has reclaimed more than $1,000,000 worth of materials. Palo Verde has made numerous changes to the DAW segregation program since its inception. To ensure that the DAW segregation program remained cost effective and in compliance with applicable regulatory guidance, segregation techniques were revised and new equipment was evaluated and procured. This paper details that effort and summarizes the operational data that has been collected

  7. How Segregation Makes Us Fat: Food Behaviors and Food Environment as Mediators of the Relationship Between Residential Segregation and Individual Body Mass Index

    Directory of Open Access Journals (Sweden)

    Melody Goodman

    2018-03-01

    Full Text Available ObjectivesRacial residential segregation affects food landscapes that dictate residents’ food environments and is associated with obesity risk factors, including individual dietary patterns and behaviors. We examine if food behaviors and environments mediate the association between segregation and body mass index (BMI.MethodsNon-Hispanic Whites and Blacks living in the St. Louis and Kansas City metro regions from 2012 to 2013 were surveyed on dietary behaviors, food environment, and BMI (n = 1,412. These data were combined with the CDC’s modified retail food environment index and 2012 American Community Survey data to calculate racial segregation using various evenness and exposure indices. Multi-level mediation analyses were conducted to determine if dietary behavior and food environment mediate the association between racial residential segregation and individual BMI.ResultsThe positive association between racial segregation and individual BMI is partially mediated by dietary behaviors and fully mediated by food environments.ConclusionRacial segregation (evenness and exposure is associated with BMI, mediated by dietary behaviors and food environment. Elements of the food environment, which form the context for dietary behaviors, are potential targets for interventions to reduce obesity in residentially segregated areas.

  8. Prokaryotic DNA segregation by an actin-like filament

    DEFF Research Database (Denmark)

    Møller-Jensen, Jakob; Bugge Jensen, Rasmus; Löwe, Jan

    2002-01-01

    The mechanisms responsible for prokaryotic DNA segregation are largely unknown. The partitioning locus (par) encoded by the Escherichia coli plasmid R1 actively segregates its replicon to daughter cells. We show here that the ParM ATPase encoded by par forms dynamic actin-like filaments with prop...... point for ParM polymerization. Hence, we provide evidence for a simple prokaryotic analogue of the eukaryotic mitotic spindle apparatus.......The mechanisms responsible for prokaryotic DNA segregation are largely unknown. The partitioning locus (par) encoded by the Escherichia coli plasmid R1 actively segregates its replicon to daughter cells. We show here that the ParM ATPase encoded by par forms dynamic actin-like filaments...

  9. Sound source localization and segregation with internally coupled ears

    DEFF Research Database (Denmark)

    Bee, Mark A; Christensen-Dalsgaard, Jakob

    2016-01-01

    to their correct sources (sound source segregation). Here, we review anatomical, biophysical, neurophysiological, and behavioral studies aimed at identifying how the internally coupled ears of frogs contribute to sound source localization and segregation. Our review focuses on treefrogs in the genus Hyla......, as they are the most thoroughly studied frogs in terms of sound source localization and segregation. They also represent promising model systems for future work aimed at understanding better how internally coupled ears contribute to sound source localization and segregation. We conclude our review by enumerating...

  10. Texture segregation, surface representation and figure-ground separation.

    Science.gov (United States)

    Grossberg, S; Pessoa, L

    1998-09-01

    A widespread view is that most texture segregation can be accounted for by differences in the spatial frequency content of texture regions. Evidence from both psychophysical and physiological studies indicate, however, that beyond these early filtering stages, there are stages of 3-D boundary segmentation and surface representation that are used to segregate textures. Chromatic segregation of element-arrangement patterns--as studied by Beck and colleagues--cannot be completely explained by the filtering mechanisms previously employed to account for achromatic segregation. An element arrangement pattern is composed of two types of elements that are arranged differently in different image regions (e.g. vertically on top and diagonally on the bottom). FACADE theory mechanisms that have previously been used to explain data about 3-D vision and figure-ground separation are here used to simulate chromatic texture segregation data, including data with equiluminant elements on dark or light homogeneous backgrounds, or backgrounds composed of vertical and horizontal dark or light stripes, or horizontal notched stripes. These data include the fact that segregation of patterns composed of red and blue squares decreases with increasing luminance of the interspaces. Asymmetric segregation properties under 3-D viewing conditions with the equiluminant elements close or far are also simulated. Two key model properties are a spatial impenetrability property that inhibits boundary grouping across regions with non-collinear texture elements and a boundary-surface consistency property that uses feedback between boundary and surface representations to eliminate spurious boundary groupings and separate figures from their backgrounds.

  11. "E Pluribus"... Separation: Deepening Double Segregation for More Students

    Science.gov (United States)

    Orfield, Gary; Kucsera, John; Siegel-Hawley, Genevieve

    2012-01-01

    This report shows segregation has increased dramatically across the country for Latino students, who are attending more intensely segregated and impoverished schools than they have for generations. The segregation increases have been the most dramatic in the West. The typical Latino student in the region attends a school where less than a quarter…

  12. Occupational Segregation by Sex: Determinants and Changes.

    Science.gov (United States)

    Beller, Andrea H.

    1982-01-01

    This study found that occupational sex segregation began to diminish during the 1970s, in conjunction with enforcement of the equal employment opportunity laws against sex discrimination in employment. The success of these laws suggests that discrimination was originally a determinant of occupational segregation. (Author/SK)

  13. Monte Carlo simulations of adsorption-induced segregation

    DEFF Research Database (Denmark)

    Christoffersen, Ebbe; Stoltze, Per; Nørskov, Jens Kehlet

    2002-01-01

    Through the use of Monte Carlo simulations we study the effect of adsorption-induced segregation. From the bulk composition, degree of dispersion and the partial pressure of the gas phase species we calculate the surface composition of bimetallic alloys. We show that both segregation and adsorption...

  14. Solute segregation during irradiation

    International Nuclear Information System (INIS)

    Wiedersich, H.; Okamoto, P.R.; Lam, N.Q.

    1977-01-01

    Irradiation at elevated temperature induces redistribution of the elements in alloys on a microstructural level. This phenomenon is caused by differences in the coupling of the various alloy constituents to the radiation-induced defect fluxes. A simple model of the segregation process based on coupled reaction-rate and diffusion equations is discussed. The model gives a good description of the experimentally observed consequences of radiation-induced segregation, including enrichment or depletion of solute elements near defect sinks such as surfaces, voids and dislocations; precipitation of second phases in solid solutions; precipitate redistribution in two-phase alloys; and effects of defect-production rates on void-swelling rates in alloys with minor solute additions

  15. Dynamics of Escherichia coli Chromosome Segregation during Multifork Replication

    DEFF Research Database (Denmark)

    Nielsen, Henrik Jørck; Youngren, Brenda; Hansen, Flemming G.

    2007-01-01

    Slowly growing Escherichia coli cells have a simple cell cycle, with replication and progressive segregation of the chromosome completed before cell division. In rapidly growing cells, initiation of replication occurs before the previous replication rounds are complete. At cell division, the chro......Slowly growing Escherichia coli cells have a simple cell cycle, with replication and progressive segregation of the chromosome completed before cell division. In rapidly growing cells, initiation of replication occurs before the previous replication rounds are complete. At cell division......, the chromosomes contain multiple replication forks and must be segregated while this complex pattern of replication is still ongoing. Here, we show that replication and segregation continue in step, starting at the origin and progressing to the replication terminus. Thus, early-replicated markers on the multiple......-branched chromosomes continue to separate soon after replication to form separate protonucleoids, even though they are not segregated into different daughter cells until later generations. The segregation pattern follows the pattern of chromosome replication and does not follow the cell division cycle. No extensive...

  16. Segregation by onset asynchrony.

    Science.gov (United States)

    Hancock, P J B; Walton, L; Mitchell, G; Plenderleith, Y; Phillips, W A

    2008-08-05

    We describe a simple psychophysical paradigm for studying figure-ground segregation by onset asynchrony. Two pseudorandom arrays of Gabor patches are displayed, to left and right of fixation. Within one array, a subset of elements form a figure, such as a randomly curving path, that can only be reliably detected when their onset is not synchronized with that of the background elements. Several findings are reported. First, for most participants, segregation required an onset asynchrony of 20-40 ms. Second, detection was no better when the figure was presented first, and thus by itself, than when the background elements were presented first, even though in the latter case the figure could not be detected in either of the two successive displays alone. Third, asynchrony segregated subsets of randomly oriented elements equally well. Fourth, asynchronous onsets aligned with the path could be discriminated from those lying on the path but not aligned with it. Fifth, both transient and sustained neural activity contribute to detection. We argue that these findings are compatible with neural signaling by synchronized rate codes. Finally, schizophrenic disorganization is associated with reduced sensitivity. Thus, in addition to bearing upon basic theoretical issues, this paradigm may have clinical utility.

  17. Grain Boundary Segregation in Metals

    CERN Document Server

    Lejcek, Pavel

    2010-01-01

    Grain boundaries are important structural components of polycrystalline materials used in the vast majority of technical applications. Because grain boundaries form a continuous network throughout such materials, their properties may limit their practical use. One of the serious phenomena which evoke these limitations is the grain boundary segregation of impurities. It results in the loss of grain boundary cohesion and consequently, in brittle fracture of the materials. The current book deals with fundamentals of grain boundary segregation in metallic materials and its relationship to the grain boundary structure, classification and other materials properties.

  18. Two critical periods in early visual cortex during figure–ground segregation

    Science.gov (United States)

    Wokke, Martijn E; Sligte, Ilja G; Steven Scholte, H; Lamme, Victor A F

    2012-01-01

    The ability to distinguish a figure from its background is crucial for visual perception. To date, it remains unresolved where and how in the visual system different stages of figure–ground segregation emerge. Neural correlates of figure border detection have consistently been found in early visual cortex (V1/V2). However, areas V1/V2 have also been frequently associated with later stages of figure–ground segregation (such as border ownership or surface segregation). To causally link activity in early visual cortex to different stages of figure–ground segregation, we briefly disrupted activity in areas V1/V2 at various moments in time using transcranial magnetic stimulation (TMS). Prior to stimulation we presented stimuli that made it possible to differentiate between figure border detection and surface segregation. We concurrently recorded electroencephalographic (EEG) signals to examine how neural correlates of figure–ground segregation were affected by TMS. Results show that disruption of V1/V2 in an early time window (96–119 msec) affected detection of figure stimuli and affected neural correlates of figure border detection, border ownership, and surface segregation. TMS applied in a relatively late time window (236–259 msec) selectively deteriorated performance associated with surface segregation. We conclude that areas V1/V2 are not only essential in an early stage of figure–ground segregation when figure borders are detected, but subsequently causally contribute to more sophisticated stages of figure–ground segregation such as surface segregation. PMID:23170239

  19. Two critical periods in early visual cortex during figure-ground segregation.

    Science.gov (United States)

    Wokke, Martijn E; Sligte, Ilja G; Steven Scholte, H; Lamme, Victor A F

    2012-11-01

    The ability to distinguish a figure from its background is crucial for visual perception. To date, it remains unresolved where and how in the visual system different stages of figure-ground segregation emerge. Neural correlates of figure border detection have consistently been found in early visual cortex (V1/V2). However, areas V1/V2 have also been frequently associated with later stages of figure-ground segregation (such as border ownership or surface segregation). To causally link activity in early visual cortex to different stages of figure-ground segregation, we briefly disrupted activity in areas V1/V2 at various moments in time using transcranial magnetic stimulation (TMS). Prior to stimulation we presented stimuli that made it possible to differentiate between figure border detection and surface segregation. We concurrently recorded electroencephalographic (EEG) signals to examine how neural correlates of figure-ground segregation were affected by TMS. Results show that disruption of V1/V2 in an early time window (96-119 msec) affected detection of figure stimuli and affected neural correlates of figure border detection, border ownership, and surface segregation. TMS applied in a relatively late time window (236-259 msec) selectively deteriorated performance associated with surface segregation. We conclude that areas V1/V2 are not only essential in an early stage of figure-ground segregation when figure borders are detected, but subsequently causally contribute to more sophisticated stages of figure-ground segregation such as surface segregation.

  20. Current status of low-level-waste-segregation technology

    International Nuclear Information System (INIS)

    Clark, D.E.; Colombo, P.; Sailor, V.L.

    1982-01-01

    The adoption of improved waste segregation practices by waste generators and burial sites will result in the improved disposal of low-level wastes (LLW) in the future. Many of the problems connected with this disposal mode are directly attributable to or aggravated by the indiscriminate mixing of various waste types in burial trenches. Thus, subsidence effects, contact with ground fluids, movement of radioactivity in the vapor phase, migration of radionuclides due to the presence of chelating agents or products of biological degradation, deleterious chemical reactions, and other problems have occurred. Regulations are currently being promulgated which will require waste segregation to a high degree at LLW burial sites. The state-of-the-art of LLW segregation technology and current practices in the USA have been surveyed at representative facilities. Favorable experience has been reported at various sites following the application of segregation controls. This paper reports on the state-of-the-art survey and addresses current and projected LLW segregation practices and their relationship to other waste management activities

  1. Class, Kinship Density, and Conjugal Role Segregation.

    Science.gov (United States)

    Hill, Malcolm D.

    1988-01-01

    Studied conjugal role segregation in 150 married women from intact families in working-class community. Found that, although involvement in dense kinship networks was associated with conjugal role segregation, respondents' attitudes toward marital roles and phase of family cycle when young children were present were more powerful predictors of…

  2. Dysfunctional MreB inhibits chromosome segregation in Escherichia coli

    DEFF Research Database (Denmark)

    Kruse, Thomas; Møller-Jensen, Jakob; Løbner-Olesen, Anders

    2003-01-01

    The mechanism of prokaryotic chromosome segregation is not known. MreB, an actin homolog, is a shape-determining factor in rod-shaped prokaryotic cells. Using immunofluorescence microscopy we found that MreB of Escherichia coli formed helical filaments located beneath the cell surface. Flow...... cytometric and cytological analyses indicated that MreB-depleted cells segregated their chromosomes in pairs, consistent with chromosome cohesion. Overexpression of wild-type MreB inhibited cell division but did not perturb chromosome segregation. Overexpression of mutant forms of MreB inhibited cell...... that MreB filaments participate in directional chromosome movement and segregation....

  3. Racial segregation patterns in selective universities

    OpenAIRE

    Peter Arcidiacono; Esteban M. Aucejo; Andrew Hussey; Kenneth Spenner

    2013-01-01

    This paper examines sorting into interracial friendships at selective universities. We show significant friendship segregation, particularly for blacks. Indeed, blacks' friendships are no more diverse in college than in high school, despite the fact that the colleges that blacks attend have substantially smaller black populations. We demonstrate that the segregation patterns occur in part because affirmative action results in large differences in the academic backgrounds of students of differ...

  4. 4-Phenylbutyric Acid Reveals Good Beneficial Effects on Vital Organ Function via Anti-Endoplasmic Reticulum Stress in Septic Rats.

    Science.gov (United States)

    Liu, Liangming; Wu, Huiling; Zang, JiaTao; Yang, Guangming; Zhu, Yu; Wu, Yue; Chen, Xiangyun; Lan, Dan; Li, Tao

    2016-08-01

    Sepsis and septic shock are the common complications in ICUs. Vital organ function disorder contributes a critical role in high mortality after severe sepsis or septic shock, in which endoplasmic reticulum stress plays an important role. Whether anti-endoplasmic reticulum stress with 4-phenylbutyric acid is beneficial to sepsis and the underlying mechanisms are not known. Laboratory investigation. State Key Laboratory of Trauma, Burns and Combined Injury. Sprague-Dawley rats. Using cecal ligation and puncture-induced septic shock rats, lipopolysaccharide-treated vascular smooth muscle cells, and cardiomyocytes, effects of 4-phenylbutyric acid on vital organ function and the relationship with endoplasmic reticulum stress and endoplasmic reticulum stress-mediated inflammation, apoptosis, and oxidative stress were observed. Conventional treatment, including fluid resuscitation, vasopressin, and antibiotic, only slightly improved the hemodynamic variable, such as mean arterial blood pressure and cardiac output, and slightly improved the vital organ function and the animal survival of septic shock rats. Supplementation of 4-phenylbutyric acid (5 mg/kg; anti-endoplasmic reticulum stress), especially administered at early stage, significantly improved the hemodynamic variables, vital organ function, such as liver, renal, and intestinal barrier function, and animal survival in septic shock rats. 4-Phenylbutyric acid application inhibited the endoplasmic reticulum stress and endoplasmic reticulum stress-related proteins, such as CCAAT/enhancer-binding protein homologous protein in vital organs, such as heart and superior mesenteric artery after severe sepsis. Further studies showed that 4-phenylbutyric acid inhibited endoplasmic reticulum stress-mediated cytokine release, apoptosis, and oxidative stress via inhibition of nuclear factor-κB, caspase-3 and caspase-9, and increasing glutathione peroxidase and superoxide dismutase expression, respectively. Anti

  5. The residential segregation patterns of whites by socioeconomic status, 2000-2011.

    Science.gov (United States)

    Sharp, Gregory; Iceland, John

    2013-07-01

    In light of increasing racial and ethnic diversity, a recent housing crisis, and deep economic recession, arguments pertaining to the role of socioeconomic status (SES) in shaping patterns of racial/ethnic segregation remain salient. Using data from the 2000 decennial census and the 2007-2011 American Community Survey, we provide new evidence on the residential segregation patterns of whites from minorities by SES (income, education, and poverty). Results from our comprehensive analyses indicate that SES matters for the segregation patterns of whites from minorities. In particular, we find that whites as a whole are less segregated from higher-SES minority group members than lower-SES ones. Among whites, those of higher SES are more segregated from blacks and Hispanics as a whole and less segregated from Asians, indicating the importance of SES differentials across racial/ethnic groups in shaping residential patterns. We also find that during the 2000s, white-black segregation remained stable or declined, while whites became more segregated from Hispanics and Asians by all SES indicators. Fixed-effects models indicate that increasing white-minority SES segregation was fueled in part by increases in a metropolitan area's immigrant and elderly populations, minority poverty rate, and home values, while declining segregation was associated with rising education levels and new housing construction. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. Segregation and Socialization: Academic Segregation and Citizenship Attitudes of Adolescents in Comparative Perspective?

    Directory of Open Access Journals (Sweden)

    Dimokritos Kavadias

    2017-07-01

    Full Text Available Purpose: There is a tendency to assess educational systems in terms of their efficiency in gaining high scores on cognitive skills. Schools perform, however, also a socializing function. The whole policy debate tends to ignore the impact of educational systems on attitudes or democratic values. This contribution focuses on the impact of the organization of education in European societies on the civic attitudes of adolescents. Design/methodology/approach: We explore the impact of academic segregation – the practice of segregating children on the basis of their scholastic achievement – on attitudes of adolescents living in different educational systems. We use the International Civic and Citizenship Education Study (2009 relying on multilevel models. Findings: Pupils differ in their outlook on fellow citizens, according to the ways in which educational systems select and differentiate throughout school careers. More specifically, there is a negative impact of academic segregation on the attitudes towards immigrants and ethnic minorities. Research limitations/implications: The experience of adolescents based on their educational achievement seems to affect how they perceive other people. We have not answered the question why this is the case. We hope to have provided a minimal indication of the impact of inequality on social outcomes.

  7. Racial Segregation and the American Foreclosure Crisis

    Science.gov (United States)

    Rugh, Jacob S.; Massey, Douglas S.

    2013-01-01

    Although the rise in subprime lending and the ensuing wave of foreclosures was partly a result of market forces that have been well-identified in the literature, in the United States it was also a highly racialized process. We argue that residential segregation created a unique niche of poor minority clients who were differentially marketed risky subprime loans that were in great demand for use in mortgage-backed securities that could be sold on secondary markets. We test this argument by regressing foreclosure actions in the top 100 U.S. metropolitan areas on measures of black, Hispanic, and Asian segregation while controlling for a variety of housing market conditions, including average creditworthiness, the extent of coverage under the Community Reinvestment Act, the degree of zoning regulation, and the overall rate of subprime lending. We find that black residential dissimilarity and spatial isolation are powerful predictors of foreclosures across U.S. metropolitan areas. In order to isolate subprime lending as the causal mechanism whereby segregation influences foreclosures, we estimate a two-stage least squares model that confirms the causal effect of black segregation on the number and rate of foreclosures across metropolitan areas. In the United States segregation was an important contributing cause of the foreclosure crisis, along with overbuilding, risky lending practices, lax regulation, and the bursting of the housing price bubble. PMID:25308973

  8. Racial Segregation and the American Foreclosure Crisis.

    Science.gov (United States)

    Rugh, Jacob S; Massey, Douglas S

    2010-10-01

    Although the rise in subprime lending and the ensuing wave of foreclosures was partly a result of market forces that have been well-identified in the literature, in the United States it was also a highly racialized process. We argue that residential segregation created a unique niche of poor minority clients who were differentially marketed risky subprime loans that were in great demand for use in mortgage-backed securities that could be sold on secondary markets. We test this argument by regressing foreclosure actions in the top 100 U.S. metropolitan areas on measures of black, Hispanic, and Asian segregation while controlling for a variety of housing market conditions, including average creditworthiness, the extent of coverage under the Community Reinvestment Act, the degree of zoning regulation, and the overall rate of subprime lending. We find that black residential dissimilarity and spatial isolation are powerful predictors of foreclosures across U.S. metropolitan areas. In order to isolate subprime lending as the causal mechanism whereby segregation influences foreclosures, we estimate a two-stage least squares model that confirms the causal effect of black segregation on the number and rate of foreclosures across metropolitan areas. In the United States segregation was an important contributing cause of the foreclosure crisis, along with overbuilding, risky lending practices, lax regulation, and the bursting of the housing price bubble.

  9. Requirements for the evaluation of computational speech segregation systems

    DEFF Research Database (Denmark)

    May, Tobias; Dau, Torsten

    2014-01-01

    Recent studies on computational speech segregation reported improved speech intelligibility in noise when estimating and applying an ideal binary mask with supervised learning algorithms. However, an important requirement for such systems in technical applications is their robustness to acoustic...... associated with perceptual attributes in speech segregation. The results could help establish a framework for a systematic evaluation of future segregation systems....

  10. Growth Conditions Regulate the Requirements for Caulobacter Chromosome Segregation

    DEFF Research Database (Denmark)

    Shebelut, Conrad W.; Jensen, Rasmus Bugge; Gitai, Zemer

    2009-01-01

    Growth environments are important metabolic and developmental regulators. Here we demonstrate a growth environment-dependent effect on Caulobacter chromosome segregation of a small-molecule inhibitor of the MreB bacterial actin cytoskeleton. Our results also implicate ParAB as important segregation...... determinants, suggesting that multiple distinct mechanisms can mediate Caulobacter chromosome segregation and that their relative contributions can be environmentally regulated....

  11. Segregation analysis of microsatellite (SSR) markers in sugarcane polyploids.

    Science.gov (United States)

    Lu, X; Zhou, H; Pan, Y-B; Chen, C Y; Zhu, J R; Chen, P H; Li, Y-R; Cai, Q; Chen, R K

    2015-12-28

    No information is available on segregation analysis of DNA markers involving both pollen and self-progeny. Therefore, we used capillary electrophoresis- and fluorescence-based DNA fingerprinting together with single pollen collection and polymerase chain reaction (PCR) to investigate simple sequence repeat (SSR) marker segregation among 964 single pollens and 288 self-progenies (S1) of sugarcane cultivar LCP 85-384. Twenty SSR DNA fragments (alleles) were amplified by five polymorphic SSR markers. Only one non-parental SSR allele was observed in 2392 PCRs. SSR allele inheritance was in accordance with Mendelian laws of segregation and independent assortment. Highly significant correlation coefficients were found between frequencies of observed and expected genotypes in pollen and S1 populations. Within the S1 population, the most frequent genotype of each SSR marker was the parental genotype of the same marker. The number of genotypes was higher in pollen than S1 population. PIC values of the five SSR markers were greater in pollen than S1 populations. Eleven of 20 SSR alleles (55%) were segregated in accordance with Mendelian segregation ratios expected from pollen and S1 populations of a 2n = 10x polyploid. Six of 20 SSR alleles were segregated in a 3:1 (presence:absence) ratio and were simplex markers. Four and one alleles were segregated in 77:4 and 143:1 ratios and considered duplex and triplex markers, respectively. Segregation ratios of remaining alleles were unexplainable. The results provide information about selection of crossing parents, estimation of seedling population optimal size, and promotion of efficient selection, which may be valuable for sugarcane breeders.

  12. Segregation effects and phase developments during solidification of alloy 625

    DEFF Research Database (Denmark)

    Højerslev, Christian; Tiedje, Niels Skat; Hald, John

    2006-01-01

    contained gamma-phase, Laves phase and, if carbon was dissolved in the liquid, niobium rich carbides formed. Molybdenum and niobium showed strong tendencies to segregate. Their segregation was balanced by inverse segregation of nickel and iron. The chromium concentration remained almost constant in gamma...

  13. Segregation practices in the management of low-level radioactive wastes

    International Nuclear Information System (INIS)

    Clark, D.E.; Colombo, P.

    1981-10-01

    A scoping study has been undertaken to determine the state-of-the-art of waste segregation technology as applied to the management of low-level waste (LLW). Present-day waste segregation practices were surveyed through a review of the recent literature and by means of personal interviews with personnel at selected facilities. Among the nuclear establishments surveyed were Department of Energy (DOE) laboratories and plants, nuclear fuel cycle plants, public and private laboratories, institutions, industrial plants, and DOE and commercially operated shallow land burial sites. These survey data were used to analyze the relationship between waste segregation practices and waste treatment/disposal processes, to assess the developmental needs for improved segregation technology, and to evaluate the costs and benefits associated with the implementation of waste segregation controls. For improved processing and disposal of LLW, it is recommended that waste segregation be practiced wherever it is technically feasible and cost-effective to do so. It is noted that LLW management practices are now undergoing rapid change such that the technology and requirements for waste segregation in the near future may differ significantly from those of the present day

  14. Radiation-induced segregation in binary and ternary alloys

    International Nuclear Information System (INIS)

    Okamoto, P.R.; Rehn, L.E.

    1979-01-01

    A review is given of our current knowledge of radiation-induced segregation of major and minor elements in simple binary and ternary alloys as derived from experimental techniques such as Auger electron spectroscopy, secondary-ion mass spectroscopy, ion-backscattering, infrared emissivity measurements and transmission electron microscopy. Measurements of the temperature, dose and dose-rate dependences as well as of the effects of such materials variables as solute solubility, solute misfit and initial solute concentration has proved particularly valuable in understanding the mechanisms of segregation. The interpretation of these data in terms of current theoretical models which link solute segregation behavior to defect-solute binding interactions and/or to the relative diffusion rates of solute and solvent atoms the interstitial and vacancy migration mechanisms has, in general, been fairly successful and has provided considerable insight into the highly interrelated phenomena of solute-defect trapping, solute segregation, phase stability and void swelling. Specific examples in selected fcc, bcc and hcp alloy systems are discussed with particular emphasis given to the effects of radiation-induced segregation on the phase stability of single-phase and two-phase binary alloys and simple Fe-Cr-Ni alloys. (Auth.)

  15. Correlates of figure-ground segregation in fMRI.

    Science.gov (United States)

    Skiera, G; Petersen, D; Skalej, M; Fahle, M

    2000-01-01

    We investigated which correlates of figure-ground-segregation can be detected by means of functional magnetic resonance imaging (fMRI). Five subjects were scanned with a Siemens Vision 1.5 T system. Motion, colour, and luminance-defined checkerboards were presented with alternating control conditions containing one of the two features of the checkerboard. We find a segregation-specific activation in V1 for all subjects and all stimuli and conclude that neural mechanisms exist as early as in the primary visual cortex that are sensitive to figure-ground segregation.

  16. Bayesian linkage and segregation analysis: factoring the problem.

    Science.gov (United States)

    Matthysse, S

    2000-01-01

    Complex segregation analysis and linkage methods are mathematical techniques for the genetic dissection of complex diseases. They are used to delineate complex modes of familial transmission and to localize putative disease susceptibility loci to specific chromosomal locations. The computational problem of Bayesian linkage and segregation analysis is one of integration in high-dimensional spaces. In this paper, three available techniques for Bayesian linkage and segregation analysis are discussed: Markov Chain Monte Carlo (MCMC), importance sampling, and exact calculation. The contribution of each to the overall integration will be explicitly discussed.

  17. A sexy spin on nonrandom chromosome segregation.

    Science.gov (United States)

    Charville, Gregory W; Rando, Thomas A

    2013-06-06

    Nonrandom chromosome segregation is an intriguing phenomenon linked to certain asymmetric stem cell divisions. In a recent report in Nature, Yadlapalli and Yamashita (2013) observe nonrandom segregation of X and Y chromosomes in Drosophila germline stem cells and shed light on the complex mechanisms of this fascinating process. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. Gender Segregation in the Retail Industry

    OpenAIRE

    Lynch, Samantha

    2002-01-01

    This paper examines the phenomenon of occupational gender segregation in the retail industry, with a particular focus on part time working. The empirical data was gathered through a series of 59 interviews, and a small survey of employees, with store level managers in three UK retail organisations. The paper illustrates the extent of occupational gender segregation and considers the impact of such stereotyping on the gender pay gap, training and career development.\\ud \\ud Occupational gender ...

  19. Figure-ground segregation in a recurrent network architecture

    NARCIS (Netherlands)

    Lamme, V.A.F.; Roelfsema, P.R.; Spekreijse, H.; Bosch, H.

    2002-01-01

    Proposes a model of how the visual brain segregate textured scenes into figures and background. During texture segregation, locations where the properties of texture elements change abruptly are assigned to boundaries, whereas image regions that are relatively homogeneous are grouped together

  20. Towards deep learning with segregated dendrites.

    Science.gov (United States)

    Guerguiev, Jordan; Lillicrap, Timothy P; Richards, Blake A

    2017-12-05

    Deep learning has led to significant advances in artificial intelligence, in part, by adopting strategies motivated by neurophysiology. However, it is unclear whether deep learning could occur in the real brain. Here, we show that a deep learning algorithm that utilizes multi-compartment neurons might help us to understand how the neocortex optimizes cost functions. Like neocortical pyramidal neurons, neurons in our model receive sensory information and higher-order feedback in electrotonically segregated compartments. Thanks to this segregation, neurons in different layers of the network can coordinate synaptic weight updates. As a result, the network learns to categorize images better than a single layer network. Furthermore, we show that our algorithm takes advantage of multilayer architectures to identify useful higher-order representations-the hallmark of deep learning. This work demonstrates that deep learning can be achieved using segregated dendritic compartments, which may help to explain the morphology of neocortical pyramidal neurons.

  1. In Vivo and In Silico Investigation Into Mechanisms of Frequency Dependence of Repolarization Alternans in Human Ventricular Cardiomyocytes.

    Science.gov (United States)

    Zhou, Xin; Bueno-Orovio, Alfonso; Orini, Michele; Hanson, Ben; Hayward, Martin; Taggart, Peter; Lambiase, Pier D; Burrage, Kevin; Rodriguez, Blanca

    2016-01-22

    Repolarization alternans (RA) are associated with arrhythmogenesis. Animal studies have revealed potential mechanisms, but human-focused studies are needed. RA generation and frequency dependence may be determined by cell-to-cell variability in protein expression, which is regulated by genetic and external factors. To characterize in vivo RA in human and to investigate in silico using human models, the ionic mechanisms underlying the frequency-dependent differences in RA behavior identified in vivo. In vivo electrograms were acquired at 240 sites covering the epicardium of 41 patients at 6 cycle lengths (600-350 ms). In silico investigations were conducted using a population of biophysically detailed human models incorporating variability in protein expression and calibrated using in vivo recordings. Both in silico and in vivo, 2 types of RA were identified, with Fork- and Eye-type restitution curves, based on RA persistence or disappearance, respectively, at fast pacing rates. In silico simulations show that RA are strongly correlated with fluctuations in sarcoplasmic reticulum calcium, because of strong release and weak reuptake. Large L-type calcium current conductance is responsible for RA disappearance at fast frequencies in Eye-type (30% larger in Eye-type versus Fork-type; Psilico, 2 types of RA are identified, with RA persistence/disappearance as frequency increases. In silico, L-type calcium current and Na(+)/Ca(2+) exchanger current determine RA human cell-to-cell differences through intracellular and sarcoplasmic reticulum calcium regulation. © 2015 The Authors.

  2. Effects of chronic administration of clenbuterol on contractile properties and calcium homeostasis in rat extensor digitorum longus muscle.

    Science.gov (United States)

    Sirvent, Pascal; Douillard, Aymerick; Galbes, Olivier; Ramonatxo, Christelle; Py, Guillaume; Candau, Robin; Lacampagne, Alain

    2014-01-01

    Clenbuterol, a β2-agonist, induces skeletal muscle hypertrophy and a shift from slow-oxidative to fast-glycolytic muscle fiber type profile. However, the cellular mechanisms of the effects of chronic clenbuterol administration on skeletal muscle are not completely understood. As the intracellular Ca2+ concentration must be finely regulated in many cellular processes, the aim of this study was to investigate the effects of chronic clenbuterol treatment on force, fatigue, intracellular calcium (Ca2+) homeostasis and Ca2+-dependent proteolysis in fast-twitch skeletal muscles (the extensor digitorum longus, EDL, muscle), as they are more sensitive to clenbuterol-induced hypertrophy. Male Wistar rats were chronically treated with 4 mg.kg-1 clenbuterol or saline vehicle (controls) for 21 days. Confocal microscopy was used to evaluate sarcoplasmic reticulum Ca2+ load, Ca2+-transient amplitude and Ca2+ spark properties. EDL muscles from clenbuterol-treated animals displayed hypertrophy, a shift from slow to fast fiber type profile and increased absolute force, while the relative force remained unchanged and resistance to fatigue decreased compared to control muscles from rats treated with saline vehicle. Compared to control animals, clenbuterol treatment decreased Ca2+-transient amplitude, Ca2+ spark amplitude and frequency and the sarcoplasmic reticulum Ca2+ load was markedly reduced. Conversely, calpain activity was increased by clenbuterol chronic treatment. These results indicate that chronic treatment with clenbuterol impairs Ca2+ homeostasis and this could contribute to the remodeling and functional impairment of fast-twitch skeletal muscle.

  3. Figure-ground segregation in a recurrent network architecture

    NARCIS (Netherlands)

    Roelfsema, Pieter R.; Lamme, Victor A. F.; Spekreijse, Henk; Bosch, Holger

    2002-01-01

    Here we propose a model of how the visual brain segregates textured scenes into figures and background. During texture segregation, locations where the properties of texture elements change abruptly are assigned to boundaries, whereas image regions that are relatively homogeneous are grouped

  4. Effects of ginger extract on smooth muscle activity of sheep reticulum and rumen

    Directory of Open Access Journals (Sweden)

    Amin Mamaghani

    2013-06-01

    Full Text Available Reticulorumen hypomotility leads to the impaired physiologic functions of the digestive tract. Prokinetic action of ginger has been demonstrated in the laboratory animals and human. The aim of this study was to evaluate the effect of hydroalcoholic extract of ginger on contraction and motility of reticulum and rumen of ruminants. Collected samples of reticulum and rumen from eight sheep were investigated in vitro. The extract at the concentration of 0.1 and 1.0 mg L-1 had no effect on any preparations. Contraction of reticulum and rumen preparations was occurred at 10.0 and 100 mg L-1 concentrations (p < 0.05. Concentration of 1000 mg L-1 caused a relaxation in preparations contracted with 10.0 and 100 mg L-1. Likewise, the concentration of 1000 mg L-1 significantly (p < 0.05 inhibited ACh-induced contraction in both tissues. Six sheep were involved in electromyographic study. Administration of 40 mg kg-1 of the extract increased the overall frequency of contractions of the reticulum and rumen at the subsequent three days with the prominent increase at the second day (p < 0.05. Results of in vitro study indicated that hydroalcoholic extract of ginger contained spasmogenic and spasmolytic constituents. The results in vivo study represented evidences that the extract may have stimulant effect on reticulorumen motility in 40 mg kg-1 concentration.

  5. Endoplasmic reticulum stress and diabetic retinopathy

    Directory of Open Access Journals (Sweden)

    Toshiyuki Oshitari

    2008-02-01

    Full Text Available Toshiyuki Oshitari1,2, Natsuyo Hata1, Shuichi Yamamoto11Department of Ophthalmology and Visual Science, Chiba University Graduate School of Medicine, Chiba City, Chiba, Japan; 2Department of Ophthalmology, Kimitsu Central Hospital, Kisarazu City, Chiba, JapanAbstract: Endoplasmic reticulum (ER stress is involved in the pathogenesis of several diseases including Alzheimer disease and Parkinson disease. Many recent studies have shown that ER stress is related to the pathogenesis of diabetes mellitus, and with the death of pancreatic β-cells, insulin resistance, and the death of the vascular cells in the retina. Diabetic retinopathy is a major complication of diabetes and results in death of both neural and vascular cells. Because the death of the neurons directly affects visual function, the precise mechanism causing the death of neurons in early diabetic retinopathy must be determined. The ideal therapy for preventing the onset and the progression of diabetic retinopathy would be to treat the factors involved with both the vascular and neuronal abnormalities in diabetic retinopathy. In this review, we present evidence that ER stress is involved in the death of both retinal neurons and vascular cells in diabetic eyes, and thus reducing or blocking ER stress may be a potential therapy for preventing the onset and the progression of diabetic retinopathy.Keywords: endoplasmic reticulum stress, diabetic retinopathy, vascular cell death, neuronal cell death

  6. Segregation in ternary alloys: an interplay of driving forces

    International Nuclear Information System (INIS)

    Luyten, J.; Helfensteyn, S.; Creemers, C.

    2003-01-01

    Monte Carlo (MC) simulations combined with the constant bond energy (CBE) model are set up to explore and understand the general segregation behaviour in ternary alloys as a function of composition and more in particular the segregation to Cu-Ni-Al (1 0 0) surfaces. Besides its simplicity, allowing swift simulations, which are necessary for a first general survey over all possible compositions, one of the advantages of the CBE model lies in the possibility to clearly identify the different driving forces for segregation. All simulations are performed in the Grand Canonical Ensemble, using a new algorithm to determine the chemical potential of the components. Notwithstanding the simplicity of the CBE model, one extra feature is evidenced: depending on the values of the interatomic interaction parameters, in some regions of the ternary diagram, a single solid solution becomes thermodynamically unstable, leading to demixing into two conjugate phases. The simulations are first done for three hypothetical systems that are however representative for real alloy systems. The three systems are characterised by different sets of interatomic interaction parameters. These extensive simulations over the entire composition range of the ternary alloy yield a 'topographical' segregation map, showing distinct regions where different species segregate. These distinct domains originate from a variable interplay between the driving forces for segregation and attractive/repulsive interactions in the bulk of the alloy. The results on these hypothetical systems are very helpful for a better understanding of the segregation behaviour in Cu-Ni-Al and other ternary alloys

  7. Charles J. McMahon Interfacial Segregation and Embrittlement Symposium

    National Research Council Canada - National Science Library

    Vitek, Vaclav

    2003-01-01

    .... McMahon Interfacial Segregation and Embrittlement Symposium: Grain Boundary Segregation and Fracture in Steels was sponsored by ASM International, Materials Science Critical Technology Sector, Structural Materials Division, Materials Processing...

  8. Residential segregation of socioeconomic variables and health indices in Iran

    Directory of Open Access Journals (Sweden)

    Seyed Saeed Hashemi Nazari

    2013-01-01

    Conclusions: Correlation of segregation of determinants of socioeconomic status with segregation of health indices is an indicator of existence of hot zones of health problems across some provinces. Further studies using multilevel modeling and individual data in health outcomes at individual level and segregation measures at appropriate geographic levels are required to confirm these relations.

  9. Multi-Contextual Segregation and Environmental Justice Research: Toward Fine-Scale Spatiotemporal Approaches.

    Science.gov (United States)

    Park, Yoo Min; Kwan, Mei-Po

    2017-10-10

    Many environmental justice studies have sought to examine the effect of residential segregation on unequal exposure to environmental factors among different social groups, but little is known about how segregation in non-residential contexts affects such disparity. Based on a review of the relevant literature, this paper discusses the limitations of traditional residence-based approaches in examining the association between socioeconomic or racial/ethnic segregation and unequal environmental exposure in environmental justice research. It emphasizes that future research needs to go beyond residential segregation by considering the full spectrum of segregation experienced by people in various geographic and temporal contexts of everyday life. Along with this comprehensive understanding of segregation, the paper also highlights the importance of assessing environmental exposure at a high spatiotemporal resolution in environmental justice research. The successful integration of a comprehensive concept of segregation, high-resolution data and fine-grained spatiotemporal approaches to assessing segregation and environmental exposure would provide more nuanced and robust findings on the associations between segregation and disparities in environmental exposure and their health impacts. Moreover, it would also contribute to significantly expanding the scope of environmental justice research.

  10. Multi-Contextual Segregation and Environmental Justice Research: Toward Fine-Scale Spatiotemporal Approaches

    Directory of Open Access Journals (Sweden)

    Yoo Min Park

    2017-10-01

    Full Text Available Many environmental justice studies have sought to examine the effect of residential segregation on unequal exposure to environmental factors among different social groups, but little is known about how segregation in non-residential contexts affects such disparity. Based on a review of the relevant literature, this paper discusses the limitations of traditional residence-based approaches in examining the association between socioeconomic or racial/ethnic segregation and unequal environmental exposure in environmental justice research. It emphasizes that future research needs to go beyond residential segregation by considering the full spectrum of segregation experienced by people in various geographic and temporal contexts of everyday life. Along with this comprehensive understanding of segregation, the paper also highlights the importance of assessing environmental exposure at a high spatiotemporal resolution in environmental justice research. The successful integration of a comprehensive concept of segregation, high-resolution data and fine-grained spatiotemporal approaches to assessing segregation and environmental exposure would provide more nuanced and robust findings on the associations between segregation and disparities in environmental exposure and their health impacts. Moreover, it would also contribute to significantly expanding the scope of environmental justice research.

  11. Phase-oriented surface segregation in an aluminium casting alloy

    International Nuclear Information System (INIS)

    Nguyen, Chuong L.; Atanacio, Armand; Zhang, Wei; Prince, Kathryn E.; Hyland, Margaret M.; Metson, James B.

    2009-01-01

    There have been many reports of the surface segregation of minor elements, especially Mg, into surface layers and oxide films on the surface of Al alloys. LM6 casting alloy (Al-12%Si) represents a challenging system to examine such segregation as the alloy features a particularly inhomogeneous phase structure. The very low but mobile Mg content (approximately 0.001 wt.%), and the surface segregation of modifiers such as Na, mean the surface composition responds in a complex manner to thermal treatment conditions. X-ray photoelectron spectroscopy (XPS) has been used to determine the distribution of these elements within the oxide film. Further investigation by dynamic secondary ion mass spectrometry (DSIMS) confirmed a strong alignment of segregated Na and Mg into distinct phases of the structure.

  12. Tributyltin induces apoptotic signaling in hepatocytes through pathways involving the endoplasmic reticulum and mitochondria

    International Nuclear Information System (INIS)

    Grondin, Melanie; Marion, Michel; Denizeau, Francine; Averill-Bates, Diana A.

    2007-01-01

    Tri-n-butyltin is a widespread environmental toxicant, which accumulates in the liver. This study investigates whether tri-n-butyltin induces pro-apoptotic signaling in rat liver hepatocytes through pathways involving the endoplasmic reticulum and mitochondria. Tri-n-butyltin activated the endoplasmic reticulum pathway of apoptosis, which was demonstrated by the activation of the protease calpain, its translocation to the plasma membrane, followed by cleavage of the calpain substrates, cytoskeletal protein vinculin, and caspase-12. Caspase-12 is localized to the cytoplasmic side of the endoplasmic reticulum and is involved in apoptosis mediated by the endoplasmic reticulum. Tri-n-butyltin also caused translocation of the pro-apoptotic proteins Bax and Bad from the cytosol to mitochondria, as well as changes in mitochondrial membrane permeability, events which can activate the mitochondrial death pathway. Tri-n-butyltin induced downstream apoptotic events in rat hepatocytes at the nuclear level, detected by chromatin condensation and by confocal microscopy using acridine orange. We investigated whether the tri-n-butyltin-induced pro-apoptotic events in hepatocytes could be linked to perturbation of intracellular calcium homeostasis, using confocal microscopy. Tri-n-butyltin caused changes in intracellular calcium distribution, which were similar to those induced by thapsigargin. Calcium was released from a subcellular compartment, which is likely to be the endoplasmic reticulum, into the cytosol. Cytosolic acidification, which is known to trigger apoptosis, also occurred and involved the Cl - /HCO 3 - exchanger. Pro-apoptotic events in hepatocytes were inhibited by the calcium chelator, Bapta-AM, and by a calpain inhibitor, which suggests that changes in intracellular calcium homeostasis are involved in tri-n-butyltin-induced apoptotic signaling in rat hepatocytes

  13. Liquid Segregation Phenomenological Behaviors of Ti14 Alloy during Semisolid Deformation

    Directory of Open Access Journals (Sweden)

    Y. N. Chen

    2014-05-01

    Full Text Available The liquid segregation phenomenon and its effect on deformation mechanism of Ti14 alloy in semisolid metal processing were investigated by thermal simulation test. Microstructure of depth profile was determined by cross-section quantitative metallography, and liquid segregation phenomenon was described by Darcy's law. The results show that segregation phenomenon was affected by solid fraction, strain rate, and deformation rate. More liquid segregated from center to edge portion with high strain rate and/or deformation ratio as well as low solid fraction, which caused different distribution of dominating deformation mechanism. The relationship between liquid segregation and main deformation mechanism was also discussed by phenomenological model.

  14. Intracellular signalling pathways in the vasoconstrictor response of mouse afferent arterioles to adenosine

    DEFF Research Database (Denmark)

    Hansen, Pernille B. Lærkegaard; Friis, Ulla Glenert; Uhrenholt, Torben Rene

    2007-01-01

    of calcium from the sarcoplasmic reticulum (SR), stimulated presumably by IP(3), is involved in the adenosine contraction mechanism of the afferent arteriole. In agreement with this notion is the observation that 2 aminoethoxydiphenyl borate (100 microM) blocked the adenosine-induced constriction whereas...... was abolished by IAA-94. Furthermore, the vasoconstriction caused by adenosine was significantly inhibited by 5 microM nifedipine (control 8.3 +/- 0.2 microM, ado 3.6 +/- 0.6 microM, ado + nifedipine 6.8 +/- 0.2 microM) suggesting involvement of voltage-dependent calcium channels. CONCLUSION: We conclude...

  15. Localization and in-vivo characterization of thapsia garganica CYP76AE2 indicates a role in thapsigargin biosynthesis

    DEFF Research Database (Denmark)

    Andersen, Trine Bundgaard; Martinez-Swatson, Karen Agatha; Rasmussen, Silas Anselm

    2017-01-01

    The Mediterranean plant Thapsia garganica (dicot, Apiaceae), also known as deadly carrot, produces the highly toxic compound thapsigargin. This compound is a potent inhibitor of the sarcoplasmic-endoplasmic reticulum Ca2+ -ATPase calcium pump in mammals and is of industrial importance as the active...... in Nicotiana benthamiana, converts epikunzeaol into epidihydrocostunolide. Furthermore, we show that thapsigargin is likely to be stored in secretory ducts in the roots. Transcripts from TgTPS2 (epikunzeaol synthase) and TgCYP76AE2 in roots were found only in the epithelial cells lining these secretory ducts...

  16. Relaxant mechanisms of 3, 5, 7, 30, 40-pentamethoxyflavone on isolated human cavernosum

    DEFF Research Database (Denmark)

    Jansakul, Chaweewan; Tachanaparuksa, Kuldej; Mulvany, Michael J.

    2012-01-01

    We have investigated effects and mechanisms responsible for the activity of 3, 5, 7, 30, 40-pentamethoxyflavone (PMF) on isolated human cavernosum. PMF is the major flavone isolated from Kaempferia parviflora claimed to act as an aphrodisiac. PMF caused relaxation of phenylephrine precontracted...... Krebs solution with nifedipine (blocker of L-type Ca2þ channels), or in Ca2þ-free Krebs solution, PMF caused a further inhibition of human cavernosum contracted with phenylephrine. In human cavernosum treated with thapsigargin (inhibitor of sarcoplasmic reticulum Ca2þ-ATPase) in Ca2þ-free medium, PMF...

  17. Somatically segregating clone of apomictic maize-tripsacum hybrid

    International Nuclear Information System (INIS)

    Yudin, B.F.; Lukina, L.A.

    1988-01-01

    The results of further study on clone AM-5, isolated in the progeny of γ-irradiated plants of the apomictic hybrid of maize with tripsacum (2n = 38) are reported. The variegated-leaf seedlings of the clone segregate somatically and produce variegated, mottled, green (phenotypically normal) plants in different ratios in the apomictic progenies. The variegated, and to a lesser degree, green segregants segregate further. The mottled apomictics as well as mottled branches of variegated seedlings maintain their phenotype on transplantation, however, these is a progressive enhancement of the characters of vegetative lethality. Lethals of two extra maize genomes to the AM-5 nucleus does not affect significantly the scope and nature of segregation. At the same time, the loss of tripsacum genome restores normal phenotype. Clone AM-5 is an example of hybrid apomictic form causing significant morphological variability, which is, nevertheless, not related with apomictic and reversion to the sexual process

  18. The residential segregation patterns of whites by socioeconomic status, 2000–2011

    Science.gov (United States)

    Sharp, Gregory; Iceland, John

    2013-01-01

    In light of increasing racial and ethnic diversity, a recent housing crisis, and deep economic recession, arguments pertaining to the role of socioeconomic status (SES) in shaping patterns of racial/ethnic segregation remain salient. Using data from the 2000 decennial census and the 2007–2011 American Community Survey, we provide new evidence on the residential segregation patterns of whites from minorities by SES (income, education, and poverty). Results from our comprehensive analyses indicate that SES matters for the segregation patterns of whites from minorities. In particular, we find that whites as a whole are less segregated from higher-SES minority group members than lower-SES ones. Among whites, those of higher SES are more segregated from blacks and Hispanics as a whole and less segregated from Asians, indicating the importance of SES differentials across racial/ethnic groups in shaping residential patterns. We also find that during the 2000s, white-black segregation remained stable or declined, while whites became more segregated from Hispanics and Asians by all SES indicators. Fixed-effects models indicate that increasing white-minority SES segregation was fueled in part by increases in a metropolitan area’s immigrant and elderly populations, minority poverty rate, and home values, while declining segregation was associated with rising education levels and new housing construction. PMID:23721673

  19. Racial Residential Segregation of School-Age Children and Adults: The Role of Schooling as a Segregating Force

    Directory of Open Access Journals (Sweden)

    Ann Owens

    2017-02-01

    Full Text Available Neighborhoods are critical contexts for children’s well-being, but differences in neighborhood inequality among children and adults are understudied. I document racial segregation between neighborhoods among school-age children and adults in 2000 and 2010 and find that though the racial composition of children’s and adults’ neighborhoods is similar, exposure to own-age neighbors varies. Compared with adults’ exposure to other adults, children are exposed to fewer white and more minority, particularly Hispanic, children. This is due in part to compositional differences, but children are also more unevenly sorted across neighborhoods by race than adults. One explanation for higher segregation among children is that parents consider school options when making residential choices. Consistent with this hypothesis, I find that school district boundaries account for a larger proportion of neighborhood segregation among children than among adults. Future research on spatial inequality must consider the multiple contexts differentially contributing to inequality among children and adults.

  20. Segregation in cast products

    Indian Academy of Sciences (India)

    Unknown

    The agreement with experimental data is mostly qualitative. The paper also ... For example, a high degree of positive segregation in the central region .... solute in a cast product, important ones being: size of casting, rate of solidification, mode.

  1. Opposing dorsal/ventral stream dynamics during figure-ground segregation.

    Science.gov (United States)

    Wokke, Martijn E; Scholte, H Steven; Lamme, Victor A F

    2014-02-01

    The visual system has been commonly subdivided into two segregated visual processing streams: The dorsal pathway processes mainly spatial information, and the ventral pathway specializes in object perception. Recent findings, however, indicate that different forms of interaction (cross-talk) exist between the dorsal and the ventral stream. Here, we used TMS and concurrent EEG recordings to explore these interactions between the dorsal and ventral stream during figure-ground segregation. In two separate experiments, we used repetitive TMS and single-pulse TMS to disrupt processing in the dorsal (V5/HMT⁺) and the ventral (lateral occipital area) stream during a motion-defined figure discrimination task. We presented stimuli that made it possible to differentiate between relatively low-level (figure boundary detection) from higher-level (surface segregation) processing steps during figure-ground segregation. Results show that disruption of V5/HMT⁺ impaired performance related to surface segregation; this effect was mainly found when V5/HMT⁺ was perturbed in an early time window (100 msec) after stimulus presentation. Surprisingly, disruption of the lateral occipital area resulted in increased performance scores and enhanced neural correlates of surface segregation. This facilitatory effect was also mainly found in an early time window (100 msec) after stimulus presentation. These results suggest a "push-pull" interaction in which dorsal and ventral extrastriate areas are being recruited or inhibited depending on stimulus category and task demands.

  2. Effective search for stable segregation configurations at grain boundaries with data-mining techniques

    Science.gov (United States)

    Kiyohara, Shin; Mizoguchi, Teruyasu

    2018-03-01

    Grain boundary segregation of dopants plays a crucial role in materials properties. To investigate the dopant segregation behavior at the grain boundary, an enormous number of combinations have to be considered in the segregation of multiple dopants at the complex grain boundary structures. Here, two data mining techniques, the random-forests regression and the genetic algorithm, were applied to determine stable segregation sites at grain boundaries efficiently. Using the random-forests method, a predictive model was constructed from 2% of the segregation configurations and it has been shown that this model could determine the stable segregation configurations. Furthermore, the genetic algorithm also successfully determined the most stable segregation configuration with great efficiency. We demonstrate that these approaches are quite effective to investigate the dopant segregation behaviors at grain boundaries.

  3. The role of temporal coherence in auditory stream segregation

    DEFF Research Database (Denmark)

    Christiansen, Simon Krogholt

    The ability to perceptually segregate concurrent sound sources and focus one’s attention on a single source at a time is essential for the ability to use acoustic information. While perceptual experiments have determined a range of acoustic cues that help facilitate auditory stream segregation......, it is not clear how the auditory system realizes the task. This thesis presents a study of the mechanisms involved in auditory stream segregation. Through a combination of psychoacoustic experiments, designed to characterize the influence of acoustic cues on auditory stream formation, and computational models...... of auditory processing, the role of auditory preprocessing and temporal coherence in auditory stream formation was evaluated. The computational model presented in this study assumes that auditory stream segregation occurs when sounds stimulate non-overlapping neural populations in a temporally incoherent...

  4. Quality-by-design (QbD): effects of testing parameters and formulation variables on the segregation tendency of pharmaceutical powder measured by the ASTM D 6940-04 segregation tester.

    Science.gov (United States)

    Xie, Lin; Wu, Huiquan; Shen, Meiyu; Augsburger, Larry L; Lyon, Robbe C; Khan, Mansoor A; Hussain, Ajaz S; Hoag, Stephen W

    2008-10-01

    The objective of this study was to examine the effects of testing parameters and formulation variables on the segregation tendency of pharmaceutical powders measured by the ASTM D 6940-04 segregation tester using design of experiments (DOE) approaches. The test blends consisted of 4% aspirin (ASP) and 96% microcrystalline cellulose (MCC) with and without magnesium stearate (MgS). The segregation tendency of a blend was determined by measuring the last/first (L/F) ratio, the ratio of aspirin concentrations between the first and last samples discharged from the tester. A 2(2) factorial design was used to determine the effects of measurement parameters [amount of material loaded (W), number of segregation cycles] with number of replicates 6. ANOVA showed that W was a critical parameter for segregation testing. The L/F value deviated further from 1 (greater segregation tendency) with increasing W. A 2(3) full factorial design was used to assess the effects of formulation variables: grade of ASP (unmilled, milled), grade of MCC, and amount of lubricant, MgS. MLR and ANOVA showed that the grade of ASP was the main effect contributing to segregation tendency. Principal Component Regression Analysis established a correlation between L/F and the physical properties of the blend related to ASP and MCC, the ASP/MCC particle size ratio (PSR) and powder cohesion. The physical properties of the blend related to density and flow were not influenced by the grade of ASP and were not related to the segregation tendency of the blend. The direct relationship between L/F and PSR was determined by univariate analysis. Segregation tendency increased as the ASP to MCC particle size increased. This study highlighted critical test parameters for segregation testing and identified critical physical properties of the blends that influence segregation tendency. (c) 2008 Wiley-Liss, Inc. and the American Pharmacists Association

  5. The Emergence of Gender Segregation in Toddler Playgroups.

    Science.gov (United States)

    Serbin, Lisa A.; And Others

    1994-01-01

    A naturalistic study of toddler playgroups examined factors that might encourage gender segregation. Results revealed that play in same-sex contexts facilitates social interaction, whereas in mixed-sex contexts, play leads to passive social relations. Toddlers who segregated were more behaviorally sex-typed. Preferences for sex-typed toys did not…

  6. Student Mobility, Segregation, and Achievement Gaps: Evidence from Clark County, Nevada

    Science.gov (United States)

    Welsh, Richard O.

    2018-01-01

    Student mobility and school segregation are two important issues with significant equity implications for urban school districts that are often addressed separately. This article examines the relationship between student mobility and school segregation. The findings indicate that more segregated schools typically have smaller within-school…

  7. Plasma membrane—endoplasmic reticulum contact sites regulate phosphatidylcholine synthesis

    NARCIS (Netherlands)

    Tavassoli, S.; Chao, J.T.; Young, B.P.; Cox, R.C.; Prinz, W.A.; de Kroon, A.I.P.M.; Loewen, C.I.R.

    2013-01-01

    Synthesis of phospholipids, sterols and sphingolipids is thought to occur at contact sites between the endoplasmic reticulum (ER) and other organelles because many lipid-synthesizing enzymes are enriched in these contacts. In only a few cases have the enzymes been localized to contacts in vivo and

  8. Chromosome and cell wall segregation in Streptococcus faecium ATCC 9790

    International Nuclear Information System (INIS)

    Higgins, M.L.; Glaser, D.; Dicker, D.T.; Zito, E.T.

    1989-01-01

    Segregation was studied by measuring the positions of autoradiographic grain clusters in chains formed from single cells containing on average less than one radiolabeled chromosome strand. The degree to which chromosomal and cell wall material cosegregated was quantified by using the methods of S. Cooper and M. Weinberger, dividing the number of chains labeled at the middle. This analysis indicated that in contrast to chromosomal segregation in Escherichia coli and, in some studies, to that in gram-positive rods, chromosomal segregation in Streptococcus faecium was slightly nonrandom and did not vary with growth rate. Results were not significantly affected by strand exchange. In contrast, labeled cell wall segregated predominantly nonrandomly

  9. Sodium Butyrate Induces Endoplasmic Reticulum Stress and Autophagy in Colorectal Cells: Implications for Apoptosis.

    Directory of Open Access Journals (Sweden)

    Jintao Zhang

    Full Text Available Butyrate, a short-chain fatty acid derived from dietary fiber, inhibits proliferation and induces cell death in colorectal cancer cells. However, clinical trials have shown mixed results regarding the anti-tumor activities of butyrate. We have previously shown that sodium butyrate increases endoplasmic reticulum stress by altering intracellular calcium levels, a well-known autophagy trigger. Here, we investigated whether sodium butyrate-induced endoplasmic reticulum stress mediated autophagy, and whether there was crosstalk between autophagy and the sodium butyrate-induced apoptotic response in human colorectal cancer cells.Human colorectal cancer cell lines (HCT-116 and HT-29 were treated with sodium butyrate at concentrations ranging from 0.5-5mM. Cell proliferation was assessed using MTT tetrazolium salt formation. Autophagy induction was confirmed through a combination of Western blotting for associated proteins, acridine orange staining for acidic vesicles, detection of autolysosomes (MDC staining, and electron microscopy. Apoptosis was quantified by flow cytometry using standard annexinV/propidium iodide staining and by assessing PARP-1 cleavage by Western blot.Sodium butyrate suppressed colorectal cancer cell proliferation, induced autophagy, and resulted in apoptotic cell death. The induction of autophagy was supported by the accumulation of acidic vesicular organelles and autolysosomes, and the expression of autophagy-associated proteins, including microtubule-associated protein II light chain 3 (LC3-II, beclin-1, and autophagocytosis-associated protein (Atg3. The autophagy inhibitors 3-methyladenine (3-MA and chloroquine inhibited sodium butyrate induced autophagy. Furthermore, sodium butyrate treatment markedly enhanced the expression of endoplasmic reticulum stress-associated proteins, including BIP, CHOP, PDI, and IRE-1a. When endoplasmic reticulum stress was inhibited by pharmacological (cycloheximide and mithramycin and genetic

  10. 7 CFR 58.332 - Segregation of raw material.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 3 2010-01-01 2010-01-01 false Segregation of raw material. 58.332 Section 58.332... Specifications for Dairy Plants Approved for USDA Inspection and Grading Service 1 Operations and Operating Procedures § 58.332 Segregation of raw material. The milk and cream received at the dairy plant shall meet...

  11. Induction of cortical endoplasmic reticulum by dimerization of a coatomer-binding peptide anchored to endoplasmic reticulum membranes

    OpenAIRE

    Lavieu, Grégory; Orci, Lelio; Shi, Lei; Geiling, Michael; Ravazzola, Mariella; Wieland, Felix; Cosson, Pierre; Rothman, James E.

    2010-01-01

    Cortical endoplasmic reticulum (cER) is a permanent feature of yeast cells but occurs transiently in most animal cell types. Ist2p is a transmembrane protein that permanently localizes to the cER in yeast. When Ist2 is expressed in mammalian cells, it induces abundant cER containing Ist2. Ist2 cytoplasmic C-terminal peptide is necessary and sufficient to induce cER. This peptide sequence resembles classic coat protein complex I (COPI) coatomer protein-binding KKXX signals, and indeed the dime...

  12. Role of endoplasmic reticulum stress in the loss of retinal ganglion cells in diabetic retinopathy

    Institute of Scientific and Technical Information of China (English)

    Liping Yang; Lemeng Wu; Dongmei Wang; Ying Li; Hongliang Dou; Mark OMTso; Zhizhong Ma

    2013-01-01

    Endoplasmic reticulum stress is closely involved in the early stage of diabetic retinopathy. In the present study, a streptozotocin-induced diabetic animal model was given an intraperitoneal injection of tauroursodeoxycholic acid. Results from immunofluorescent co-localization experiments showed that both caspase-12 protein and c-Jun N-terminal kinase 1 phosphorylation levels significantly in-creased, which was associated with retinal ganglion celldeath in diabetic retinas. The C/ERB ho-mologous protein pathway directly contributed to glial reactivity, and was subsequently responsible for neuronal loss and vascular abnormalities in diabetic retinopathy. Our experimental findings in-dicate that endoplasmic reticulum stress plays an important role in diabetes-induced retinal neu-ronal loss and vascular abnormalities, and that inhibiting the activation of the endoplasmic reticulum stress pathway provides effective protection against diabetic retinopathy.

  13. Irradiation-induced segregation in multi-component alloys

    International Nuclear Information System (INIS)

    Chen, I.W.

    1983-01-01

    A unified analysis of irradiation-induced segregation in multi-component alloys is developed using the formulation of irreversible thermodynamics. Three distinct mechanisms for segregation, namely the inverse Kirkendall effect, the vacancy-wind effect, and the solute drag of interstitials, are identified. In particular, the inverse Kirkendall effect due to interstitials arises only if a solute-interstitial interaction or a mutual conversion among interstitials via lattice atom intermediaries operates simultaneously. In the limit of fast conversion a para-equilibrium state may be reached between interstitials and lattice atoms, and the interstitial mechanism becomes formally analogous to the vacancy mechanism. Although the past treatment of rate phenomena in this field was apparently limited to the latter case, the importance of the consideration of separate chemical potentials for interstitials of different species, in segregation and other irradiation effects, is emphasized. (orig.)

  14. School Segregation and Racial Academic Achievement Gaps

    Directory of Open Access Journals (Sweden)

    Sean F. Reardon

    2016-09-01

    Full Text Available Although it is clear that racial segregation is linked to academic achievement gaps, the mechanisms underlying this link have been debated since James Coleman published his eponymous 1966 report. In this paper, I examine sixteen distinct measures of segregation to determine which is most strongly associated with academic achievement gaps. I find clear evidence that one aspect of segregation in particular—the disparity in average school poverty rates between white and black students’ schools—is consistently the single most powerful correlate of achievement gaps, a pattern that holds in both bivariate and multivariate analyses. This implies that high-poverty schools are, on average, much less effective than lower-poverty schools and suggests that strategies that reduce the differential exposure of black, Hispanic, and white students to poor schoolmates may lead to meaningful reductions in academic achievement gaps.

  15. Comparing the influence of spectro-temporal integration in computational speech segregation

    DEFF Research Database (Denmark)

    Bentsen, Thomas; May, Tobias; Kressner, Abigail Anne

    2016-01-01

    The goal of computational speech segregation systems is to automatically segregate a target speaker from interfering maskers. Typically, these systems include a feature extraction stage in the front-end and a classification stage in the back-end. A spectrotemporal integration strategy can...... be applied in either the frontend, using the so-called delta features, or in the back-end, using a second classifier that exploits the posterior probability of speech from the first classifier across a spectro-temporal window. This study systematically analyzes the influence of such stages on segregation...... metric that comprehensively predicts computational segregation performance and correlates well with intelligibility. The outcome of this study could help to identify the most effective spectro-temporal integration strategy for computational segregation systems....

  16. Post-Slavery? Post-Segregation? Post-Racial? A History of the Impact of Slavery, Segregation, and Racism on the Education of African Americans

    Science.gov (United States)

    Span, Christopher M.

    2015-01-01

    This chapter details how slavery, segregation, and racism impacted the educational experiences of African Americans from the colonial era to the present. It argues that America has yet to be a truly post-slavery and post-segregation society, let alone a post-racial society.

  17. Kinetics of radiation-induced segregation in ternary alloys

    International Nuclear Information System (INIS)

    Lam, N.O.; Kumar, A.; Wiedersich, H.

    1982-01-01

    Model calculations of radiation-induced segregation in ternary alloys have been performed, using a simple theory. The theoretical model describes the coupling between the fluxes of radiation-induced defects and alloying elements in an alloy A-B-C by partitioning the defect fluxes into those occurring via A-, B-, and C-atoms, and the atom fluxes into those taking place via vacancies and interstitials. The defect and atom fluxes can be expressed in terms of concentrations and concentration gradients of all the species present. With reasonable simplifications, the radiation-induced segregation problem can be cast into a system of four coupled partial-differential equations, which can be solved numerically for appropriate initial and boundary conditions. Model calculations have been performed for ternary solid solutions intended to be representative of Fe-Cr-Ni and Ni-Al-Si alloys under various irradiation conditions. The dependence of segregation on both the alloy properties and the irradiation variables, e.g., temperature and displacement rate, was calculated. The sample calculations are in good qualitative agreement with the general trends of radiation-induced segregation observed experimentally

  18. Flow Induced segregation in full scale castings with SCC

    DEFF Research Database (Denmark)

    Thrane, Lars Nyholm; Stang, Henrik; Geiker, Mette Rica

    2007-01-01

    induced segregation is a major risk during casting and it is not yet clear how this phenomenon should be modelled. In this paper testing and numerical simulations of full-scale wall castings are compared. Two different SCCs and three different filling methods were applied resulting in different flow...... patterns during form filling. Results show that the flow patterns have a major influence on the risk of flow induced segregation and the surface finish of the hardened concrete. A hypothesis for the mechanism of flow induced segregation is put forth....

  19. Auditory Figure-Ground Segregation is Impaired by High Visual Load

    OpenAIRE

    Lavie, Nilli; Chait, Maria; Molloy, Katharine

    2017-01-01

    Figure-ground segregation is fundamental to listening in complex acoustic environments. An ongoing debate pertains to whether segregation requires attention or is 'automatic' and pre-attentive. In this magnetoencephalography (MEG) study we tested a prediction derived from Load Theory of attention (1) that segregation requires attention, but can benefit from the automatic allocation of any 'leftover' capacity under low load. Complex auditory scenes were modelled with Stochastic Figure Ground s...

  20. Framing Hostilities: Analysis of Mission Statements from Segregated Chicana/o Schools

    Science.gov (United States)

    Orozco, Richard

    2012-01-01

    This study examined discourses used in mission statements from segregated Chicana/o and White schools. The words and phrases used in segregated Chicana/o school mission statements produce negatively oriented frames that make transparent low expectations and negative attitudes compared to those used in segregated White schools. These frames become…

  1. Particle segregation in pneumatic conveying lines

    Energy Technology Data Exchange (ETDEWEB)

    McGlinchey, D.; Marjanovic, P.; Cook, S.; Jones, M.G. [Glasgow Caledonian University, Glasgow (United Kingdom). Centre for Industrial Bulk Solids Handling

    2000-07-01

    This investigation studied segregation of particles during pneumatic transport from a theoretical and experimental perspective. Dilute phase or suspension flow and dense phase (non-suspension flow) were both considered. A computer model was generated based on the conservation equations to investigate dilute phase conditions; an initial qualitative investigation of material behaviour being conveyed in dense phase was made with plastic pellets and salt as a segregating mixture in a small test rig and the results from a full scale test rig conveying two grades of coal of different size distributions are discussed. 11 refs., 9 figs., 1 tab.

  2. Comparisons between different techniques for measuring mass segregation

    Science.gov (United States)

    Parker, Richard J.; Goodwin, Simon P.

    2015-06-01

    We examine the performance of four different methods which are used to measure mass segregation in star-forming regions: the radial variation of the mass function {M}_MF; the minimum spanning tree-based ΛMSR method; the local surface density ΣLDR method; and the ΩGSR technique, which isolates groups of stars and determines whether the most massive star in each group is more centrally concentrated than the average star. All four methods have been proposed in the literature as techniques for quantifying mass segregation, yet they routinely produce contradictory results as they do not all measure the same thing. We apply each method to synthetic star-forming regions to determine when and why they have shortcomings. When a star-forming region is smooth and centrally concentrated, all four methods correctly identify mass segregation when it is present. However, if the region is spatially substructured, the ΩGSR method fails because it arbitrarily defines groups in the hierarchical distribution, and usually discards positional information for many of the most massive stars in the region. We also show that the ΛMSR and ΣLDR methods can sometimes produce apparently contradictory results, because they use different definitions of mass segregation. We conclude that only ΛMSR measures mass segregation in the classical sense (without the need for defining the centre of the region), although ΣLDR does place limits on the amount of previous dynamical evolution in a star-forming region.

  3. A new principle of figure-ground segregation : The accentuation

    NARCIS (Netherlands)

    Pinna, Baingio; Reeves, Adam; Koenderink, Jan; van Doorn, Andrea; Deiana, Katia

    2018-01-01

    The problem of perceptual organization was studied by Gestalt psychologists in terms of figure-ground segregation. In this paper we explore a new principle of figure-ground segregation: accentuation. We demonstrate the effectiveness of accentuation relative to other Gestalt principles, and also

  4. Titanium Dioxide Nanoparticles Induce Endoplasmic Reticulum Stress-Mediated Autophagic Cell Death via Mitochondria-Associated Endoplasmic Reticulum Membrane Disruption in Normal Lung Cells

    Science.gov (United States)

    Yu, Kyeong-Nam; Chang, Seung-Hee; Park, Soo Jin; Lim, Joohyun; Lee, Jinkyu; Yoon, Tae-Jong; Kim, Jun-Sung; Cho, Myung-Haing

    2015-01-01

    Nanomaterials are used in diverse fields including food, cosmetic, and medical industries. Titanium dioxide nanoparticles (TiO2-NP) are widely used, but their effects on biological systems and mechanism of toxicity have not been elucidated fully. Here, we report the toxicological mechanism of TiO2-NP in cell organelles. Human bronchial epithelial cells (16HBE14o-) were exposed to 50 and 100 μg/mL TiO2-NP for 24 and 48 h. Our results showed that TiO2-NP induced endoplasmic reticulum (ER) stress in the cells and disrupted the mitochondria-associated endoplasmic reticulum membranes (MAMs) and calcium ion balance, thereby increasing autophagy. In contrast, an inhibitor of ER stress, tauroursodeoxycholic acid (TUDCA), mitigated the cellular toxic response, suggesting that TiO2-NP promoted toxicity via ER stress. This novel mechanism of TiO2-NP toxicity in human bronchial epithelial cells suggests that further exhaustive research on the harmful effects of these nanoparticles in relevant organisms is needed for their safe application. PMID:26121477

  5. Income Segregation between Schools and School Districts. CEPA Working Paper No. 16-04

    Science.gov (United States)

    Owens, Ann; Reardon, Sean F.; Jencks, Christopher

    2016-01-01

    Although trends in the racial segregation of schools are well documented, less is known about trends in "income" segregation. We use multiple data sources to document trends in income segregation between schools and school districts. Between-district income segregation of families with children enrolled in public school increased by over…

  6. Preimplantation genetic diagnosis outcomes and meiotic segregation analysis of robertsonian translocation carriers.

    Science.gov (United States)

    Ko, Duck Sung; Cho, Jae Won; Lee, Hyoung-Song; Kim, Jin Yeong; Kang, Inn Soo; Yang, Kwang Moon; Lim, Chun Kyu

    2013-04-01

    To investigate the meiotic segregation patterns of cleavage-stage embryos from robertsonian translocation carriers and aneuploidy of chromosome 18 according to meiotic segregation patterns. Retrospective study. Infertility center and laboratory of reproductive biology and infertility. Sixty-two couples with robertsonian translocation carriers. One blastomere was biopsied from embryos and diagnosed with the use of fluorescence in situ hybridization (FISH). Translocation chromosomes were analyzed with the use of locus-specific and subtelomeric FISH probes. Aneuploidy of chromosome 18 was assessed simultaneously with translocation chromosomes. Preimplantation genetic diagnosis (PGD) outcomes, meiotic segregation patterns of robertsonian translocation, and aneuploidy of chromosome 18 depending on meiotic segregation patterns. Two hundred seventy embryos of 332 transferrable embryos were transferred in 113 cycles, and 27 healthy babies were born. The alternate segregation was significantly higher in male carriers than in female carriers (43.9% vs. 29.9%, respectively), and adjacent segregation was higher in female carriers than in male carriers (44.7% vs. 38.7%, respectively). Aneuploidy of chromosome 18 was significantly increased in 3:0-segregated or chaotic embryos. Forty-seven alternate embryos were excluded from embryo replacement owing to aneuploidy of chromosome 18. In carriers of robertsonian translocation, meiotic segregation showed differences between men and women. Frequent meiotic errors caused by premature predivision or nondisjunction and less stringent checkpoint in women might cause such differences between sexes. Aneuploidy of chromosome 18 might be influenced by meiotic segregation of translocation chromosomes. Factors that cause malsegregation, such as 3:0 or chaotic segregation, seem to play a role in aneuploidy of chromosome 18. Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  7. Ghrelin Ameliorates Asthma by Inhibiting Endoplasmic Reticulum Stress.

    Science.gov (United States)

    Fu, Tian; Wang, Lei; Zeng, Qingdi; Zhang, Yan; Sheng, Baowei; Han, Liping

    2017-12-01

    This study aimed to confirm the ameliorative effect of ghrelin on asthma and investigate its mechanism. The murine model of asthma was induced by ovalbumin (OVA) treatment and assessed by histological pathology and airway responsiveness to methacholine. The total and differential leukocytes were counted. Tumor necrosis factor α, interferon γ, interleukin-5 and interleukin-13 levels in bronchoalveolar lavage fluid were quantified by commercial kits. The protein levels in pulmonary tissues were measured by Western blot analysis. Ghrelin ameliorated the histological pathology and airway hyperresponsiveness in the OVA-induced asthmatic mouse model. Consistently, OVA-increased total and differential leukocytes and levels of tumor necrosis factor α, interferon γ, interleukin-5 and interleukin-13 in bronchoalveolar lavage fluid were significantly attenuated by ghrelin. Ghrelin prevented the increased protein levels of the endoplasmic reticulum stress markers glucose regulated protein 78 and CCAAT/enhancer binding protein homologous protein and reversed the reduced levels of p-Akt in asthmatic mice. Ghrelin might prevent endoplasmic reticulum stress activation by stimulating the Akt signaling pathway, which attenuated inflammation and ameliorated asthma in mice. Ghrelin might be a new target for asthma therapy. Copyright © 2017. Published by Elsevier Inc.

  8. Endoplasmic reticulum stress causes EBV lytic replication

    OpenAIRE

    Taylor, Gwen Marie; Raghuwanshi, Sandeep K.; Rowe, David T.; Wadowsky, Robert M.; Rosendorff, Adam

    2011-01-01

    Endoplasmic reticulum (ER) stress triggers a homeostatic cellular response in mammalian cells to ensure efficient folding, sorting, and processing of client proteins. In lytic-permissive lymphoblastoid cell lines (LCLs), pulse exposure to the chemical ER-stress inducer thapsigargin (TG) followed by recovery resulted in the activation of the EBV immediate-early (BRLF1, BZLF1), early (BMRF1), and late (gp350) genes, gp350 surface expression, and virus release. The protein phosphatase 1 a (PP1a)...

  9. Capturing the two dimensions of residential segregation at the neighborhood level for health research

    Directory of Open Access Journals (Sweden)

    Masayoshi eOka

    2014-08-01

    Full Text Available Two conceptual and methodological foundations of segregation studies are that (i segregation involves more than one group, and (ii segregation measures need to quantify how different population groups are distributed across space. Therefore, percentage of population belonging to a group is not an appropriate measure of segregation because it does not describe how populations are spread across different areal units or neighborhoods. In principle, evenness and isolation are the two distinct dimensions of segregation that capture the spatial patterns of population groups. To portray people’s daily environment more accurately, segregation measures need to account for the spatial relationships between areal units and to reflect the situations at the neighborhood scale. For these reasons, the use of local spatial entropy-based diversity index (SHi and local spatial isolation index (Si to capture the evenness and isolation dimensions of segregation, respectively, are preferable. However, these two local spatial segregation indexes have rarely been incorporated into health research. Rather ineffective and insufficient segregation measures have been used in previous studies. Hence, this paper empirically demonstrates how the two measures can reflect the two distinct dimensions of segregation at the neighborhood level, and argues conceptually and set the stage for their future use to effectively and meaningfully examine the relationships between residential segregation and health.

  10. Segregation of granular binary mixtures by a ratchet mechanism.

    Science.gov (United States)

    Farkas, Zénó; Szalai, Ferenc; Wolf, Dietrich E; Vicsek, Tamás

    2002-02-01

    We report on a segregation scheme for granular binary mixtures, where the segregation is performed by a ratchet mechanism realized by a vertically shaken asymmetric sawtooth-shaped base in a quasi-two-dimensional box. We have studied this system by computer simulations and found that most binary mixtures can be segregated using an appropriately chosen ratchet, even when the particles in the two components have the same size and differ only in their normal restitution coefficient or friction coefficient. These results suggest that the components of otherwise nonsegregating granular mixtures may be separated using our method.

  11. Surface, segregation profile for Ni50Pd50(100)

    DEFF Research Database (Denmark)

    Christensen, Asbjørn; Ruban, Andrei; Skriver, Hans Lomholt

    1997-01-01

    A recent dynamical LEED study [G.N. Derry, C.B. McVey, P.J. Rous, Surf. Sci. 326 (1995) 59] reported an oscillatory surface segregation profile in the Ni50Pd50(100) system with the surface layer enriched by Pd. We have performed ab-initio total-energy calculations for the surface of this alloy...... system using the coherent potential approximation and obtain an oscillatory segregation profile, in agreement with experiments. We discuss the energetic origin of the oscillatory segregation profile in terms of effective cluster interactions. We include relaxation effects by means of the semi...

  12. Analysis of endoplasmic reticulum of tobacco cells using confocal microscopy

    Czech Academy of Sciences Publication Activity Database

    Radochová, Barbora; Janáček, Jiří; Schwarzerová, K.; Demjénová, E.; Tomori, Z.; Karen, Petr; Kubínová, Lucie

    2005-01-01

    Roč. 24, č. 11 (2005), s. 181-185 ISSN 1580-3139 R&D Projects: GA AV ČR(CZ) KJB6011309 Institutional research plan: CEZ:AV0Z50110509 Keywords : confocal microscopy * endoplasmic reticulum * image analysis Subject RIV: EA - Cell Biology

  13. Purely temporal figure-ground segregation.

    Science.gov (United States)

    Kandil, F I; Fahle, M

    2001-05-01

    Visual figure-ground segregation is achieved by exploiting differences in features such as luminance, colour, motion or presentation time between a figure and its surround. Here we determine the shortest delay times required for figure-ground segregation based on purely temporal features. Previous studies usually employed stimulus onset asynchronies between figure- and ground-containing possible artefacts based on apparent motion cues or on luminance differences. Our stimuli systematically avoid these artefacts by constantly showing 20 x 20 'colons' that flip by 90 degrees around their midpoints at constant time intervals. Colons constituting the background flip in-phase whereas those constituting the target flip with a phase delay. We tested the impact of frequency modulation and phase reduction on target detection. Younger subjects performed well above chance even at temporal delays as short as 13 ms, whilst older subjects required up to three times longer delays in some conditions. Figure-ground segregation can rely on purely temporal delays down to around 10 ms even in the absence of luminance and motion artefacts, indicating a temporal precision of cortical information processing almost an order of magnitude lower than the one required for some models of feature binding in the visual cortex [e.g. Singer, W. (1999), Curr. Opin. Neurobiol., 9, 189-194]. Hence, in our experiment, observers are unable to use temporal stimulus features with the precision required for these models.

  14. Chemical segregation and self polarisation in ferroelectrics

    Directory of Open Access Journals (Sweden)

    Bernard E. Watts

    2009-06-01

    Full Text Available Chemical partitioning or segregation is commonly encountered in solid-state syntheses. It is driven by compositional, thermal and electric field gradients. These phenomena can be quite extreme in thin films and lead to notable effects on the electrical properties of ferroelectrics. The segregation in ferroelectric thin films will be illustrated and the mechanisms explained in terms of diffusion processes driven by a potential gradient of the oxygen. The hypothesis can also explain self polarisation and imprint in ferroelectric hysteresis.

  15. Radiation-induced segregation and phase stability in ferritic-martensitic alloy T 91

    Energy Technology Data Exchange (ETDEWEB)

    Wharry, Janelle P.; Jiao Zhijie; Shankar, Vani [University of Michigan, 2355 Bonisteel Blvd, Ann Arbor, MI 48109-2104 (United States); Busby, Jeremy T. [Oak Ridge National Laboratory, 1 Bethel Valley Rd, Oak Ridge, TN 37831 (United States); Was, Gary S., E-mail: gsw@umich.edu [University of Michigan, 2355 Bonisteel Blvd, Ann Arbor, MI 48109-2104 (United States)

    2011-10-01

    Radiation-induced segregation in ferritic-martensitic alloy T 91 was studied to understand the behavior of solutes as a function of dose and temperature. Irradiations were conducted using 2 MeV protons to doses of 1, 3, 7 and 10 dpa at 400 deg. C. Radiation-induced segregation at prior austenite grain boundaries was measured, and various features of the irradiated microstructure were characterized, including grain boundary carbide coverage, the dislocation microstructure, radiation-induced precipitation and irradiation hardening. Results showed that Cr, Ni and Si segregate to prior austenite grain boundaries at low dose, but segregation ceases and redistribution occurs above 3 dpa. Grain boundary carbide coverage mirrors radiation-induced segregation. Irradiation induces formation of Ni-Si-Mn and Cu-rich precipitates that account for the majority of irradiation hardening. Radiation-induced segregation behavior is likely linked to the evolution of the precipitate and dislocation microstructures.

  16. Patterns of Residential Segregation.

    Directory of Open Access Journals (Sweden)

    Rémi Louf

    Full Text Available The spatial distribution of income shapes the structure and organisation of cities and its understanding has broad societal implications. Despite an abundant literature, many issues remain unclear. In particular, all definitions of segregation are implicitely tied to a single indicator, usually rely on an ambiguous definition of income classes, without any consensus on how to define neighbourhoods and to deal with the polycentric organization of large cities. In this paper, we address all these questions within a unique conceptual framework. We avoid the challenge of providing a direct definition of segregation and instead start from a definition of what segregation is not. This naturally leads to the measure of representation that is able to identify locations where categories are over- or underrepresented. From there, we provide a new measure of exposure that discriminates between situations where categories co-locate or repel one another. We then use this feature to provide an unambiguous, parameter-free method to find meaningful breaks in the income distribution, thus defining classes. Applied to the 2014 American Community Survey, we find 3 emerging classes-low, middle and higher income-out of the original 16 income categories. The higher-income households are proportionally more present in larger cities, while lower-income households are not, invalidating the idea of an increased social polarisation. Finally, using the density-and not the distance to a center which is meaningless in polycentric cities-we find that the richer class is overrepresented in high density zones, especially for larger cities. This suggests that density is a relevant factor for understanding the income structure of cities and might explain some of the differences observed between US and European cities.

  17. Thermoelectric SQUID method for the detection of segregations

    Science.gov (United States)

    Hinken, Johann H.; Tavrin, Yury

    2000-05-01

    Aero engine turbine discs are most critical parts. Material inhomogeneities can cause disc fractures during the flight with fatal air disasters. Nondestructive testing (NDT) of the discs in various machining steps is necessary and performed as well as possible. Conventional NDT methods, however, like eddy current testing and ultrasonic testing have unacceptable limits. For example, subsurface segregations often cannot be detected directly but only indirectly in such cases when cracks already have developed from them. This may be too late. A new NDT method, which we call the Thermoelectric SQUID Method, has been developed. It allows for the detection of metallic inclusions within non-ferromagnetic metallic base material. This paper describes the results of a feasibility study on aero engine turbine discs made from Inconel® 718. These contained segregations that had been detected before by anodic etching. With the Thermoelectric SQUID Method, these segregations were detected again, and further segregations below the surfaces have been found, which had not been detected before. For this new NDT method the disc material is quasi-transparent. The Thermoelectric SQUID Method is also useful to detect distributed and localized inhomogeneities in pure metals like niobium sheets for particle accelerators.

  18. Segregating photoelastic particles in free-surface granular flows

    Science.gov (United States)

    Thomas, Amalia; Vriend, Nathalie; Environmental; Industrial Fluid Dynamics Team

    2017-11-01

    We present results from a novel experimental set-up creating 2D avalanches of photoelastic discs. Two distinct hoppers supply either monodisperse or bidisperse particles at adjustable flow-rates into a 2 meter long, narrow acrylic chute inclined at 20°. For 20-40 seconds the avalanche maintains a steady-state that accelerates and thins downstream. The chute basal roughness is variable, allowing for different flow profiles. Using a set of polarizers and a high-speed camera, we visualize and quantify the forces due to dynamic interactions between the discs using photoelastic theory. Velocity and density profiles are derived from particle tracking at different distances from the discharge point and are coarse-grained to obtain continuous fields. With the access to both force information and dynamical properties via particle-tracking, we can experimentally validate existing mu(I) and non-local rheologies. As an extension, we probe the effect of granular segregation in bimodal mixtures by using the two separate inflow hoppers. We derive the state of segregation along the avalanche channel and measure the segregation velocities of each species. This provides insight in, and a unique validation of, the fundamental physical processes that drive segregation in avalanching geometries.

  19. Associations of neighborhood-level racial residential segregation with adverse pregnancy outcomes.

    Science.gov (United States)

    Salow, Arturo D; Pool, Lindsay R; Grobman, William A; Kershaw, Kiarri N

    2018-03-01

    Previous analyses utilizing birth certificate data have shown environmental factors such as racial residential segregation may contribute to disparities in adverse pregnancy outcomes. However, birth certificate data are ill equipped to reliably differentiate among small for gestational age, spontaneous preterm birth, and medically indicated preterm birth. We sought to utilize data from electronic medical records to determine whether residential segregation among Black women is associated with an increased risk of adverse pregnancy outcomes. The study population was composed of 4770 non-Hispanic Black women who delivered during the years 2009 through 2013 at a single urban medical center. Addresses were geocoded at the level of census tract, and this tract was used to determine the degree of residential segregation for an individual's neighborhood. Residential segregation was measured using the Gi* statistic, a z-score that measures the extent to which the neighborhood racial composition deviates from the composition of the larger surrounding area. The Gi* statistic z-scores were categorized as follows: low (z  1.96). Adverse pregnancy outcomes included overall preterm birth, spontaneous preterm birth, medically indicated preterm birth, and small for gestational age. Hierarchical logistic regression models accounting for clustering by census tract and repeated births among mothers were used to estimate odds ratios of adverse pregnancy outcomes associated with segregation. In high segregation areas, the prevalence of overall preterm birth was significantly higher than that in low segregation areas (15.5% vs 10.7%, respectively; P < .001). Likewise, the prevalence of spontaneous preterm birth and medically indicated preterm birth were higher in high (9.5% and 6.0%) vs low (6.2% and 4.6%) segregation neighborhoods (P < .001 and P = .046, respectively). The associations of high segregation with overall preterm birth (odds ratio, 1.31; 95% confidence interval, 1

  20. Regulation of calcium release from the endoplasmic reticulum by the serine hydrolase ABHD2.

    Science.gov (United States)

    Yun, Bogeon; Lee, HeeJung; Powell, Roger; Reisdorph, Nichole; Ewing, Heather; Gelb, Michael H; Hsu, Ku-Lung; Cravatt, Benjamin F; Leslie, Christina C

    2017-09-02

    The serine hydrolase inhibitors pyrrophenone and KT195 inhibit cell death induced by A23187 and H 2 O 2 by blocking the release of calcium from the endoplasmic reticulum and mitochondrial calcium uptake. The effect of pyrrophenone and KT195 on these processes is not due to inhibition of their known targets, cytosolic phospholipase A 2 and α/β-hydrolase domain-containing (ABHD) 6, respectively, but represent off-target effects. To identify targets of KT195, fibroblasts were treated with KT195-alkyne to covalently label protein targets followed by click chemistry with biotin azide, enrichment on streptavidin beads and tryptic peptide analysis by mass spectrometry. Although several serine hydrolases were identified, α/β-hydrolase domain-containing 2 (ABHD2) was the only target in which both KT195 and pyrrophenone competed for binding to KT195-alkyne. ABHD2 is a serine hydrolase with a predicted transmembrane domain consistent with its pull-down from the membrane proteome. Subcellular fractionation showed localization of ABHD2 to the endoplasmic reticulum but not to mitochondria or mitochondrial-associated membranes. Knockdown of ABHD2 with shRNA attenuated calcium release from the endoplasmic reticulum, mitochondrial calcium uptake and cell death in fibroblasts stimulated with A23187. The results describe a novel mechanism for regulating calcium transfer from the endoplasmic reticulum to mitochondria that involves the serine hydrolase ABHD2. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Self-organized Segregation on the Grid

    Science.gov (United States)

    Omidvar, Hamed; Franceschetti, Massimo

    2018-02-01

    We consider an agent-based model with exponentially distributed waiting times in which two types of agents interact locally over a graph, and based on this interaction and on the value of a common intolerance threshold τ , decide whether to change their types. This is equivalent to a zero-temperature ising model with Glauber dynamics, an asynchronous cellular automaton with extended Moore neighborhoods, or a Schelling model of self-organized segregation in an open system, and has applications in the analysis of social and biological networks, and spin glasses systems. Some rigorous results were recently obtained in the theoretical computer science literature, and this work provides several extensions. We enlarge the intolerance interval leading to the expected formation of large segregated regions of agents of a single type from the known size ɛ >0 to size ≈ 0.134. Namely, we show that for 0.433sites can be observed within any sufficiently large region of the occupied percolation cluster. The exponential bounds that we provide also imply that complete segregation, where agents of a single type cover the whole grid, does not occur with high probability for p=1/2 and the range of intolerance considered.

  2. Acrolein Induces Endoplasmic Reticulum Stress and Causes Airspace Enlargement

    Science.gov (United States)

    Hanaoka, Masayuki; Natarajan, Ramesh; Kraskauskas, Donatas; Voelkel, Norbert F.

    2012-01-01

    Background Given the relative abundance and toxic potential of acrolein in inhaled cigarette smoke, it is surprising how little is known about the pulmonary and systemic effects of acrolein. Here we test the hypothesis whether systemic administration of acrolein could cause endoplasmic reticulum (ER) stress, and lung cell apoptosis, leading to the enlargement of the alveolar air spaces in rats. Methods Acute and chronic effects of intraperitoneally administered acrolein were tested. Mean alveolar airspace area was measured by using light microscopy and imaging system software. TUNEL staining and immunohistochemistry (IHC) for active caspase 3 and Western blot analysis for active caspase 3, and caspase 12 were performed to detect apoptosis. The ER-stress related gene expression in the lungs was determined by Quantitative real-time PCR analysis. Acrolein-protein adducts in the lung tissue were detected by IHC. Results Acute administration of acrolein caused a significant elevation of activated caspase 3, upregulation of VEGF expression and induced ER stress proteins in the lung tissue. The chronic administration of acrolein in rats led to emphysematous lung tissue remodeling. TUNEL staining and IHC for cleaved caspase 3 showed a large number of apoptotic septal cells in the acrolein-treated rat lungs. Chronic acrolein administration cause the endoplasmic reticulum stress response manifested by significant upregulation of ATF4, CHOP and GADd34 expression. In smokers with COPD there was a considerable accumulation of acrolein-protein adducts in the inflammatory, airway and vascular cells. Conclusions Systemic administration of acrolein causes endoplasmic reticulum stress response, lung cell apoptosis, and chronic administration leads to the enlargement of the alveolar air spaces and emphysema in rats. The substantial accumulation of acrolein-protein adducts in the lungs of COPD patients suggest a role of acrolein in the pathogenesis of emphysema. PMID:22675432

  3. Study of the Formation Mechanism of A-Segregation Based on Microstructural Morphology

    Science.gov (United States)

    Zhang, Zhao; Bao, Yuchong; Liu, Lin; Pian, Song; Li, Ri

    2018-04-01

    A model that combines a cellular automaton (CA) and lattice Boltzmann method (LBM) is presented. The mechanism of A-segregation in an Fe-0.34 wt pct C alloy ingot is analyzed on the basis of microstructural morphology calculations. The CA is used to capture the solid/liquid interface, while the LBM is used to calculate the transport phenomena. (1) The solidification of global columnar dendrites was simulated, and two obvious A-segregation bands appeared in the middle-radius region between the ingot wall surface and the centerline. In addition, the angle of deflection to the centerline increased with the increasing heat dissipation rate of the wall surface. When natural convection was ignored, the A-segregation disappeared, and only positive segregation was present in the center and bottom corner of the ingot. (2) Mixed columnar-equiaxed solidification was simulated. Many A-segregation bands appeared in the ingot. (3) Global equiaxed solidification was simulated, and no A-segregation bands were found. The results show that the upward movement of the high-concentration melt is the key to the formation of A-segregation bands, and remelting and the emergence of equiaxed grains are not necessary conditions to develop these bands. However, the appearance of equiaxed grains accelerates the formation of vortexes; thus, many A-segregation bands appear during columnar-equiaxed solidification.

  4. The role of temporal resolution in modulation-based speech segregation

    DEFF Research Database (Denmark)

    May, Tobias; Bentsen, Thomas; Dau, Torsten

    2015-01-01

    speech and noise activity on the basis of individual time-frequency (T-F) units. One important parameter of the segregation system is the window duration of the analysis-synthesis stage, which determines the lower limit of modulation frequencies that can be represented but also the temporal acuity...... with which the segregation system can manipulate individual T-F units. To clarify the consequences of this trade-off on modulation-based speech segregation performance, the influence of the window duration was systematically investigated...

  5. Membrane depolarization increases ryanodine sensitivity to Ca2+ release to the cytosol in L6 skeletal muscle cells: Implications for excitation-contraction coupling.

    Science.gov (United States)

    Pitake, Saumitra; Ochs, Raymond S

    2016-04-01

    The dihydropyridine receptor in the plasma membrane and the ryanodine receptor in the sarcoplasmic reticulum are known to physically interact in the process of excitation-contraction coupling. However, the mechanism for subsequent Ca(2+) release through the ryanodine receptor is unknown. Our lab has previously presented evidence that the dihydropyridine receptor and ryanodine receptor combine as a channel for the entry of Ca(2+) under resting conditions, known as store operated calcium entry. Here, we provide evidence that depolarization during excitation-contraction coupling causes the dihydropyridine receptor to disengage from the ryanodine receptor. The newly freed ryanodine receptor can then transport Ca(2+) from the sarcoplasmic reticulum to the cytosol. Experimentally, this should more greatly expose the ryanodine receptor to exogenous ryanodine. To examine this hypothesis, we titrated L6 skeletal muscle cells with ryanodine in resting and excited (depolarized) states. When L6 muscle cells were depolarized with high potassium or exposed to the dihydropyridine receptor agonist BAYK-8644, known to induce dihydropyridine receptor movement within the membrane, ryanodine sensitivity was enhanced. However, ryanodine sensitivity was unaffected when Ca(2+) was elevated without depolarization by the ryanodine receptor agonist chloromethylcresol, or by increasing Ca(2+) concentration in the media. Ca(2+) entry currents (from the extracellular space) during excitation were strongly inhibited by ryanodine, but Ca(2+) entry currents in the resting state were not. We conclude that excitation releases the ryanodine receptor from occlusion by the dihydropyridine receptor, enabling Ca(2+) release from the ryanodine receptor to the cytosol. © 2015 by the Society for Experimental Biology and Medicine.

  6. Immune responsiveness and incidence of reticulum cell sarcoma in long-term syngeneic radiation chimeras

    International Nuclear Information System (INIS)

    Adorini, L.; Gorini, G.; Covelli, V.; Ballardin, E.; di Michele, A.; Bassani, B.; Metalli, P.; Doria, G.

    1976-01-01

    Long-term syngeneic radiation chimeras displayed a very low incidence of reticulum cell sarcoma as compared with control mice. Immune reactivity of these animals was studied in vivo by anti-dinitrophenyl antibody titer and affinity and in vitro by mitotic responsiveness to phytohemagglutinin, concanavalin A and lipopolysaccharide. Antibody titer and affinity as well as the response to T lectins were found to be increased in chimeras. These results were attributed to increased function of mature T2 cells, which could explain the reduced incidence of reticulum cell sarcoma in chimeras

  7. Micro segregation and homogenization treatments of uranium-niobium alloys (U-Nb)

    International Nuclear Information System (INIS)

    Leal, Jose Fernando

    1988-01-01

    In the following sections micro segregation results in 0-3,6 wt% Nb and U-6,1 wt% Nb alloys casted in no consumable electrode arc furnace are presented. The micro segregation is studied qualitatively by optical microscopy and quantitatively by electron microprobe. The degree of homogenization has been measured after 800 and 850 deg C heat treatments in tubular resistive furnace. The microstructures after heat treatments are quantitatively analysed to check effects on the casting structures, mainly the variations in solute along the dendrite arm spacing. Some solidification phenomena are then discussed on reference to theoretical models of dendritic solidification , including microstructure and micro segregation. The experimental results are compared to theoretical on basis of initial and residual micro segregation after homogenization treatments. The times required for homogenization of the alloys are also discussed in function of the micro segregation from casting structures and the temperatures of the treatments. (author)

  8. Measures of social segregation in the context of Warsaw, Berlin and Paris metropolitan areas

    Directory of Open Access Journals (Sweden)

    Grzegorczyk Anna

    2015-09-01

    Full Text Available Social segregation is a subject common in contemporary studies of metropolitan areas. Until recently, studies of segregation focused on the distribution of ethnic groups, immigrants, and the poor. Today, they also cover additional indicators such as demographic properties, education, and affiliation with social and professional categories, which can also serve to determine the causes of the segregation (including the self-segregation of the rich. This article aims to point out the measures of segregation that present the segregation levels in the most complete manner, along with their application in the context of three European metropolitan areas: Warsaw, Berlin, and Paris. The first part of the article is a review of the existing approaches to segregation measures, followed by the selection of research method, presentation of the analysis’ results, and evaluation of the applied methods; presenting the opportunities and limitations in research of the social segregation phenomenon.

  9. Quantification of interfacial segregation by analytical electron microscopy

    CERN Document Server

    Muellejans, H

    2003-01-01

    The quantification of interfacial segregation by spatial difference and one-dimensional profiling is presented in general where special attention is given to the random and systematic uncertainties. The method is demonstrated for an example of Al-Al sub 2 O sub 3 interfaces in a metal-ceramic composite material investigated by energy-dispersive X-ray spectroscopy and electron energy loss spectroscopy in a dedicated scanning transmission electron microscope. The variation of segregation measured at different interfaces by both methods is within the uncertainties, indicating a constant segregation level and interfacial phase formation. The most important random uncertainty is the counting statistics of the impurity signal whereas the specimen thickness introduces systematic uncertainties (via k factor and effective scan width). The latter could be significantly reduced when the specimen thickness is determined explicitly. (orig.)

  10. Chlorhexidine-induced apoptosis or necrosis in L929 fibroblasts: A role for endoplasmic reticulum stress

    International Nuclear Information System (INIS)

    Faria, Gisele; Cardoso, Cristina R.B.; Larson, Roy E.; Silva, Joao S.; Rossi, Marcos A.

    2009-01-01

    Chlorhexidine (CHX), widely used as antiseptic and therapeutic agent in medicine and dentistry, has a toxic effect both in vivo and in vitro. The intrinsic mechanism underlying CHX-induced cytotoxicity in eukaryotic cells is, however, still unknown. A recent study from our laboratory has suggested that CHX may induce death in cultured L929 fibroblasts via endoplasmic reticulum (ER) stress. This hypothesis was further tested by means of light and electron microscopy, quantification of apoptosis and necrosis by flow cytometry, fluorescence visualization of the cytoskeleton and endoplasmic reticulum, and evaluation of the expression of 78-kDa glucose-regulated protein 78 (Grp78), a marker of activation of the unfolded protein response (UPR) in cultured L929 fibroblasts. Our finding showing increased Grp 78 expression in CHX-treated cells and the results of flow cytometry, cytoskeleton and endoplasmic reticulum fluorescence visualization, and scanning and transmission electron microscopy allowed us to suggest that CHX elicits accumulation of proteins in the endoplasmic reticulum, which causes ER overload, resulting in ER stress and cell death either by necrosis or apoptosis. It must be pointed out, however, that this does not necessarily mean that ER stress is the only way that CHX kills L929 fibroblasts, but rather that ER stress is an important target or indicator of cell death induced by this drug

  11. Segregation effect of radiation induced crosslinking of HDPE: morphology change

    International Nuclear Information System (INIS)

    Deng Pengyang; Zhong Xiaoguang

    2000-01-01

    Scanning Electronic Microscopy has been used to study morphology of pure gel; sol-gel blend and sol-gel segregation samples of radiation induced crosslinking of HDPE. The results show that the morphology of segregation sample is the same as that of pure gel and different from that of sol-gel blend. This kind of morphology change proves that the sol-gel blend have occurred a liquid---solid phase segregation in the melting state. The liquid phase (sol) will naturally immersed in the network of the gel. (author)

  12. Atomic scale study of grain boundary segregation before carbide nucleation in Ni-Cr-Fe Alloys

    Science.gov (United States)

    Li, Hui; Xia, Shuang; Liu, Wenqing; Liu, Tingguang; Zhou, Bangxin

    2013-08-01

    Three dimensional chemical information concerning grain boundary segregation before carbide nucleation was characterized by atom probe tomography in two Ni-Cr-Fe alloys which were aged at 500 °C for 0.5 h after homogenizing treatment. B, C and Si atoms segregation at grain boundary in Alloy 690 was observed. B, C, N and P atoms segregation at grain boundary in 304 austenitic stainless steel was observed. C atoms co-segregation with Cr atoms at the grain boundaries both in Alloy 690 and 304 austenitic stainless steel was found, and its effect on the carbide nucleation was discussed. The amount of each segregated element at grain boundaries in the two Ni-Cr-Fe alloys were analyzed quantitatively. Comparison of the grain boundary segregation features of the two Ni-Cr-Fe alloys were carried out based on the experimental results. The impurity and solute atoms segregate inhomogeneously in the same grain boundary both in 304 SS and Alloy 690. The grain boundary segregation tendencies (Sav) are B (11.8 ± 1.4) > P (5.4 ± 1.4) > N (4.7 ± 0.3) > C (3.7 ± 0.4) in 304 SS, and B (6.9 ± 0.9) > C (6.7 ± 0.4) > Si (1.5 ± 0.2) in Alloy 690. Cr atoms may co-segregate with C atoms at grain boundaries before carbide nucleation at the grain boundaries both in 304 SS and Alloy 690. Ni atoms generally deplete at grain boundary both in 304 SS and Alloy 690. The literature shows that the Ni atoms may co-segregate with P atoms at grain boundaries [28], but the P atoms segregation do not leads to Ni segregation in the current study. In the current study, Fe atoms may segregate or deplete at grain boundary in Alloy 690. But Fe atoms generally deplete at grain boundary in 304 SS. B atoms have the strongest grain boundary segregation tendency both in 304 SS and Alloy 690. The grain boundary segregation tendency and Gibbs free energy of B in 304 SS is higher than in Alloy 690. C atoms are easy to segregate at grain boundaries both in 304 SS and Alloy 690. The grain boundary segregation

  13. Degrees of Difference: Gender Segregation of U.S. Doctorates by Field and Program Prestige

    Directory of Open Access Journals (Sweden)

    Kim A. Weeden

    2017-02-01

    Full Text Available Women earn nearly half of doctoral degrees in research fields, yet doctoral education in the United States remains deeply segregated by gender. We argue that in addition to the oft-noted segregation of men and women by field of study, men and women may also be segregated across programs that differ in their prestige. Using data on all doctorates awarded in the United States from 2003 to 2014, field-specific program rankings, and field-level measures of math and verbal skills, we show that (1 "net" field segregation is very high and strongly associated with field-level math skills; (2 "net" prestige segregation is weaker than field segregation but still a nontrivial form of segregation in doctoral education; (3 women are underrepresented among graduates of the highest-and to a lesser extent, the lowest-prestige programs; and (4 the strength and pattern of prestige segregation varies substantially across fields, but little of this variation is associated with field skills.

  14. Microstructural characterization and formation mechanism of abnormal segregation band of hot rolled ferrite/pearlite steel

    Energy Technology Data Exchange (ETDEWEB)

    Feng, Rui [School of Materials Science and Engineering, Shandong University, Jinan 250061 (China); Engineering Research Center of Large Size Alloy Structural Steel Bars of Shandong Province, Jinan 250061 (China); School of Materials Science and Engineering, Shandong University of Technology, Zibo 255049 (China); Li, Shengli, E-mail: lishengli@sdu.edu.cn [School of Materials Science and Engineering, Shandong University, Jinan 250061 (China); Engineering Research Center of Large Size Alloy Structural Steel Bars of Shandong Province, Jinan 250061 (China); Zhu, Xinde [School of Materials Science and Engineering, Shandong University, Jinan 250061 (China); Ao, Qing [School of Materials Science and Engineering, Shandong University, Jinan 250061 (China); Engineering Research Center of Large Size Alloy Structural Steel Bars of Shandong Province, Jinan 250061 (China)

    2015-10-15

    In order to further reveal the microstructural characterization and formation mechanism of abnormal segregation band of hot rolled ferrite/pearlite steel, the microstructure of this type steel was intensively studied with Scanning Auger Microprobe (SAM), etc. The results show that severe C–Mn segregation exists in the abnormal segregation band region at the center of hot rolled ferrite/pearlite steel, which results from the Mn segregation during solidification process of the continuous casting slab. The C–Mn segregation causes relative displacement of pearlite transformation curve and bainite transformation curve of C curve in the corresponding region, leading to bay-like shaped C curve. The bay-like shaped C curve creates conditions for the transformation from supercooling austenite to bainite at relatively lower cooling rate in this region. The Fe–Mn–C Atomic Segregation Zone (FASZ) caused by C–Mn segregation can powerfully retard the atomic motion, and increase the lattice reconstruction resistance of austenite transformation. These two factors provide thermodynamic and kinetic conditions for the bainite transformation, and result in the emergence of granular bainitic abnormal segregation band at the center of steel plate, which leads to lower plasticity and toughness of this region, and induces the layered fracture. - Highlights: • Scanning Auger Microprobe (SAM) is applied in the fracture analysis. • The abnormal segregation band region appears obvious C–Mn segregation. • The C–Mn segregation leads to bay-like shaped C curve. • The C–Mn segregation leads to Fe–Mn–C Atomic Segregation Zone.

  15. Particle-size segregation and diffusive remixing in shallow granular avalanches

    Science.gov (United States)

    Gray, J. M. N. T.; Chugunov, V. A.

    2006-12-01

    Segregation and mixing of dissimilar grains is a problem in many industrial and pharmaceutical processes, as well as in hazardous geophysical flows, where the size-distribution can have a major impact on the local rheology and the overall run-out. In this paper, a simple binary mixture theory is used to formulate a model for particle-size segregation and diffusive remixing of large and small particles in shallow gravity-driven free-surface flows. This builds on a recent theory for the process of kinetic sieving, which is the dominant mechanism for segregation in granular avalanches provided the density-ratio and the size-ratio of the particles are not too large. The resulting nonlinear parabolic segregation remixing equation reduces to a quasi-linear hyperbolic equation in the no-remixing limit. It assumes that the bulk velocity is incompressible and that the bulk pressure is lithostatic, making it compatible with most theories used to compute the motion of shallow granular free-surface flows. In steady-state, the segregation remixing equation reduces to a logistic type equation and the ‘S’-shaped solutions are in very good agreement with existing particle dynamics simulations for both size and density segregation. Laterally uniform time-dependent solutions are constructed by mapping the segregation remixing equation to Burgers equation and using the Cole Hopf transformation to linearize the problem. It is then shown how solutions for arbitrary initial conditions can be constructed using standard methods. Three examples are investigated in which the initial concentration is (i) homogeneous, (ii) reverse graded with the coarse grains above the fines, and, (iii) normally graded with the fines above the coarse grains. Time-dependent two-dimensional solutions are also constructed for plug-flow in a semi-infinite chute.

  16. Grain-size segregation and levee formation in geophysical mass flows

    Science.gov (United States)

    Johnson, C.G.; Kokelaar, B.P.; Iverson, Richard M.; Logan, M.; LaHusen, R.G.; Gray, J.M.N.T.

    2012-01-01

    Data from large-scale debris-flow experiments are combined with modeling of particle-size segregation to explain the formation of lateral levees enriched in coarse grains. The experimental flows consisted of 10 m3 of water-saturated sand and gravel, which traveled ∼80 m down a steeply inclined flume before forming an elongated leveed deposit 10 m long on a nearly horizontal runout surface. We measured the surface velocity field and observed the sequence of deposition by seeding tracers onto the flow surface and tracking them in video footage. Levees formed by progressive downslope accretion approximately 3.5 m behind the flow front, which advanced steadily at ∼2 m s−1during most of the runout. Segregation was measured by placing ∼600 coarse tracer pebbles on the bed, which, when entrained into the flow, segregated upwards at ∼6–7.5 cm s−1. When excavated from the deposit these were distributed in a horseshoe-shaped pattern that became increasingly elevated closer to the deposit termination. Although there was clear evidence for inverse grading during the flow, transect sampling revealed that the resulting leveed deposit was strongly graded laterally, with only weak vertical grading. We construct an empirical, three-dimensional velocity field resembling the experimental observations, and use this with a particle-size segregation model to predict the segregation and transport of material through the flow. We infer that coarse material segregates to the flow surface and is transported to the flow front by shear. Within the flow head, coarse material is overridden, then recirculates in spiral trajectories due to size-segregation, before being advected to the flow edges and deposited to form coarse-particle-enriched levees.

  17. Aversive Racism and Intergroup Contact Theories: Cultural Competence in a Segregated World

    Science.gov (United States)

    Rodenborg, Nancy A.; Boisen, Laura A.

    2013-01-01

    The United States remains highly segregated, and social work students are likely to live and work in segregated contexts. What implications does this have for their cultural competence? Does segregation affect social workers' ability to serve diverse clients without bias? This article reviews two social psychology theories, aversive racism…

  18. Maximal voluntary contraction force, SR function and glycogen resynthesis during the first 72 h after a high-level competitive soccer game

    DEFF Research Database (Denmark)

    Krustrup, Peter; Ørtenblad, Niels; Nielsen, Joachim

    2011-01-01

    The aim of this study was to examine maximal voluntary knee-extensor contraction force (MVC force), sarcoplasmic reticulum (SR) function and muscle glycogen levels in the days after a high-level soccer game when players ingested an optimised diet. Seven high-level male soccer players had a vastus...... lateralis muscle biopsy and a blood sample collected in a control situation and at 0, 24, 48 and 72 h after a competitive soccer game. MVC force, SR function, muscle glycogen, muscle soreness and plasma myoglobin were measured. MVC force sustained over 1 s was 11 and 10% lower (P ...

  19. Surface segregation energies in transition-metal alloys

    DEFF Research Database (Denmark)

    Ruban, Andrei; Skriver, Hans Lomholt; Nørskov, Jens Kehlet

    1999-01-01

    We present a database of 24 x 24 surface segregation energies of single transition metal impurities in transition-metal hosts obtained by a Green's-function linear-muffin-tin-orbitals method in conjunction with the coherent potential and atomic sphere approximations including a multipole correction...... to the electrostatic potential and energy. We use the database to establish the major factors which govern surface segregation in transition metal alloys. We find that the calculated trends are well described by Friedel's rectangular state density model and that the few but significant deviations from the simple...

  20. Proteomic study of muscle sarcoplasmic proteins using AUT-PAGE/SDS-PAGE as two-dimensional gel electrophoresis.

    Science.gov (United States)

    Picariello, Gianluca; De Martino, Alessandra; Mamone, Gianfranco; Ferranti, Pasquale; Addeo, Francesco; Faccia, Michele; Spagnamusso, Salvatore; Di Luccia, Aldo

    2006-03-20

    In the present study, an alternative procedure for two-dimensional (2D) electrophoretic analysis in proteomic investigation of the most represented basic muscle water-soluble proteins is suggested. Our method consists of Acetic acid-Urea-Triton polyacrylamide gel (AUT-PAGE) analysis in the first dimension and standard sodium dodecyl sulphate polyacrylamide gel (SDS-PAGE) in the second dimension. Although standard two-dimensional Immobilized pH Gradient-Sodium Dodecyl-Sulphate (2D IPG-SDS) gel electrophoresis has been successfully used to study these proteins, most of the water-soluble proteins are spread on the alkaline part of the 2D map and are poorly focused. Furthermore, the similarity in their molecular weights impairs resolution of the classical approach. The addition of Triton X-100, a non-ionic detergent, into the gel induces a differential electrophoretic mobility of proteins as a result of the formation of mixed micelles between the detergent and the hydrophobic moieties of polypeptides, separating basic proteins with a criterion similar to reversed phase chromatography based on their hydrophobicity. The acid pH induces positive net charges, increasing with the isoelectric point of proteins, thus allowing enhanced resolution in the separation. By using 2D AUT-PAGE/SDS electrophoresis approach to separate water-soluble proteins from fresh pork and from dry-cured products, we could spread proteins over a greater area, achieving a greater resolution than that obtained by IPG in the pH range 3-10 and 6-11. Sarcoplasmic proteins undergoing proteolysis during the ripening of products were identified by Matrix Assisted Laser Desorption/Ionization-Time of Flight (MALDI-ToF) mass spectrometry peptide mass fingerprinting in a easier and more effective way. Two-dimensional AUT-PAGE/SDS electrophoresis has allowed to simplify separation of sarcoplasmic protein mixtures making this technique suitable in the defining of quality of dry-cured pork products by immediate

  1. The impact of exploiting spectro-temporal context in computational speech segregation

    DEFF Research Database (Denmark)

    Bentsen, Thomas; Kressner, Abigail Anne; Dau, Torsten

    2018-01-01

    Computational speech segregation aims to automatically segregate speech from interfering noise, often by employing ideal binary mask estimation. Several studies have tried to exploit contextual information in speech to improve mask estimation accuracy by using two frequently-used strategies that (1...... for measured intelligibility. The findings may have implications for the design of speech segregation systems, and for the selection of a cost function that correlates with intelligibility....

  2. Sphingosine inhibits the sarco(endo)plasmic reticulum Ca"2"+-ATPase (SERCA) activity

    International Nuclear Information System (INIS)

    Benaim, Gustavo; Pimentel, Adriana A.; Felibertt, Pimali; Mayora, Adriana; Colman, Laura; Sojo, Felipe; Rojas, Héctor; De Sanctis, Juan B.

    2016-01-01

    The increase in the intracellular Ca"2"+ concentration ([Ca"2"+]_i) is the key variable for many different processes, ranging from regulation of cell proliferation to apoptosis. In this work we demonstrated that the sphingolipid sphingosine (Sph) increases the [Ca"2"+]_i by inhibiting the sarco(endo)plasmic reticulum Ca"2"+-ATPase (SERCA), in a similar manner to thapsigargin (Tg), a specific inhibitor of this Ca"2"+ pump. The results showed that addition of sphingosine produced a release of Ca"2"+ from the endoplasmic reticulum followed by a Ca"2"+ entrance from the outside mileu. The results presented in this work support that this sphingolipid could control the activity of the SERCA, and hence sphingosine may participate in the regulation of [Ca"2"+]_I in mammalian cells.

  3. Whole-exome sequencing of a pedigree segregating asthma

    Directory of Open Access Journals (Sweden)

    DeWan Andrew T

    2012-10-01

    Full Text Available Abstract Background Despite the success of genome-wide association studies for asthma, few, if any, definitively causal variants have been identified and there is still a substantial portion of the heritability of the disease yet to be discovered. Some of this “missing heritability” may be accounted for by family-specific coding variants found to be segregating with asthma. Methods To identify family-specific variants segregating with asthma, we recruited one family from a previous study of asthma as reporting multiple asthmatic and non-asthmatic children. We performed whole-exome sequencing on all four children and both parents and identified coding variants segregating with asthma that were not found in other variant databases. Results Ten novel variants were identified that were found in the two affected offspring and affected mother, but absent in the unaffected father and two unaffected offspring. Of these ten, variants in three genes (PDE4DIP, CBLB, and KALRN were deemed of particular interest based on their functional prediction scores and previously reported function or asthma association. We did not identify any common risk variants segregating with asthma, however, we did observe an increase in the number of novel, nonsynonymous variants in asthma candidate genes in the asthmatic children compared to the non-asthmatic children. Conclusions This is the first report applying exome sequencing to identify asthma susceptibility variants. Despite having sequenced only one family segregating asthma, we have identified several potentially functional variants in interesting asthma candidate genes. This will provide the basis for future work in which more families will be sequenced to identify variants across families that cluster within genes.

  4. Increased spontaneous mitotic segregation in MMS-sensitive mutants of Saccharomyces cerevisiae

    International Nuclear Information System (INIS)

    Prakash, S.; Prakash, L.

    1977-01-01

    Methyl methanesulfonate (MMS)-sensitive mutants of Saccharomyces cerevisiae belonging to four different complementation groups, when homozygous, increase the rate of spontaneous mitotic segregation to canavanine resistance from heterozygous sensitive (can/sup r//+) diploids by 13- to 170-fold. The mms8-1 mutant is MMS and x-ray sensitive and increases the rate of spontaneous mitotic segregation 170-fold. The mms9-1 and mms13-1 mutants are sensitive to x rays and uv, respectively, in addition to MMS, and increase the rate of spontaneous mitotic segregation by 13-fold and 85-fold, respectively. The mutant mms21-1 is sensitive to MMS, x rays and uv and increases the rate of spontaneous mitotic segregation 23-fold

  5. Effect of geometric base roughness on size segregation

    Directory of Open Access Journals (Sweden)

    Jing L.

    2017-01-01

    Full Text Available The geometric roughness at boundaries has a profound impact on the dynamics of granular flows. For a bumpy base made of fixed particles, two major factors have been separately studied in the literature, namely, the size and spatial distribution of base particles. A recent work (Jing et al. 2016 has proposed a roughness indicator Ra, which combines both factors for any arbitrary bumpy base comprising equally-sized spheres. It is shown in mono-disperse flows that as Ra increases, a transition occurs from slip (Ra 0.62 conditions. This work focuses on such a phase transition in bi-disperse flows, in which Ra can be a function of time. As size segregation takes place, large particles migrate away from the bottom, leading to a variation of size ratio between flow- and base-particles. As a result, base roughness Ra evolves with the progress of segregation. Consistent with the slip/non-slip transition in mono-disperse flows, basal sliding arises at low values of Ra and the development of segregation might be affected; when Ra increases to a certain level (Ra > 0.62, non-slip condition is respected. This work extends the validity of Ra to bi-disperse flows, which can be used to understand the geometric boundary effect during segregation.

  6. Standardized Testing and School Segregation: Like Tinder for Fire?

    Science.gov (United States)

    Knoester, Matthew; Au, Wayne

    2017-01-01

    Recent research suggests that high-stakes standardized testing has played a negative role in the segregation of children by race and class in schools. In this article we review research on the overall effects of segregation, the positive and negative aspects of how desegregation plans were carried out following the 1954 Supreme Court decision…

  7. Gel-based phosphoproteomics analysis of sarcoplasmic proteins in postmortem porcine muscle with pH decline rate and time differences

    DEFF Research Database (Denmark)

    Huang, Honggang; Larsen, Martin Røssel; Karlsson, Anders H

    2011-01-01

    phosphorylation in sarcoplasmic proteins from three groups of pigs with different pH decline rates from PM 1 to 24¿h. Globally, the fast pH decline group had the highest phosphorylation level at PM 1¿h, but lowest at 24¿h, whereas the slow pH decline group showed the reverse case. The same pattern was also...... observed in most individual bands in 1-DE. The protein phosphorylation levels of 12 bands were significantly affected by the synergy effects of pH and time (p......Meat quality development is highly influenced by the pH decline caused by the postmortem (PM) glycolysis. Protein phosphorylation is an important mechanism in regulating the activity of glycometabolic enzymes. Here, a gel-based phosphoproteomic study was performed to analyze the protein...

  8. Control of segregation in squeeze cast Al-4.5Cu binary alloy

    Energy Technology Data Exchange (ETDEWEB)

    Durrant, G. [Oxford Univ. (United Kingdom). Dept. of Materials; Gallerneault, M. [Alcan International Ltd., Kingston, ON (Canada); Cantor, B. [Oxford Univ. (United Kingdom). Dept. of Materials

    1997-10-01

    The high pressure applied in squeeze casting allows Al alloys of wrought composition to be cast to near net-shape, although their long freezing range leads to the segregation of alloying elements. In this paper we present results on the squeeze casting and gravity casting of a model Al-4.5 wt%Cu alloy. Squeeze cast Al-4.5Cu has a normal segregation pattern with eutectic macrosegregates towards the centre of the billet, whereas gravity cast material has a typical inverse segregation pattern. Normal segregation in squeeze cast Al-4.5Cu is due to large temperature gradients during solidification. Segregation can be minimized by releasing the applied pressure during solidification to allow backflow of the interdendritic fluid, or by the addition of grain refiner to remove the large columnar dendritic growth structure. (orig.)

  9. Neural Dynamics of Feedforward and Feedback Processing in Figure-Ground Segregation

    OpenAIRE

    Oliver W. Layton; Ennio eMingolla; Arash eYazdanbakhsh

    2014-01-01

    Determining whether a region belongs to the interior or exterior of a shape (figure-ground segregation) is a core competency of the primate brain, yet the underlying mechanisms are not well understood. Many models assume that figure-ground segregation occurs by assembling progressively more complex representations through feedforward connections, with feedback playing only a modulatory role. We present a dynamical model of figure-ground segregation in the primate ventral stream wherein feedba...

  10. Minimization and segregation of radioactive wastes

    International Nuclear Information System (INIS)

    1992-07-01

    The report will serve as one of a series of technical manuals providing reference material and direct know-how to staff in radioisotope user establishments and research centres in Member States without nuclear power and the associated range of complex waste management operations. Considerations are limited to the minimization and segregation of wastes, these being initial steps on which the efficiency of the whole waste management system depends. The minimization and segregation operations are examined in the context of the restricted quantities and predominantly shorter lived activities of wastes from nuclear research, production and usage of radioisotopes. Liquid and solid wastes only are considered in the report. Gaseous waste minimization and treatment are specialized subjects and are not examined in this document. Gaseous effluent treatment in facilities handling low and intermediate level radioactive materials has been already the subject of a detailed IAEA report. Management of spent sealed sources has specifically been covered in a previous manual. Conditioned sealed sources must be taken into account in segregation arrangements for interim storage and disposal where there are exceptional long lived highly radiotoxic isotopes, particularly radium or americium. These are unlikely ever to be suitable for shallow land burial along with the remaining wastes. 30 refs, 5 figs, 8 tabs

  11. Audiovisual segregation in cochlear implant users.

    Directory of Open Access Journals (Sweden)

    Simon Landry

    Full Text Available It has traditionally been assumed that cochlear implant users de facto perform atypically in audiovisual tasks. However, a recent study that combined an auditory task with visual distractors suggests that only those cochlear implant users that are not proficient at recognizing speech sounds might show abnormal audiovisual interactions. The present study aims at reinforcing this notion by investigating the audiovisual segregation abilities of cochlear implant users in a visual task with auditory distractors. Speechreading was assessed in two groups of cochlear implant users (proficient and non-proficient at sound recognition, as well as in normal controls. A visual speech recognition task (i.e. speechreading was administered either in silence or in combination with three types of auditory distractors: i noise ii reverse speech sound and iii non-altered speech sound. Cochlear implant users proficient at speech recognition performed like normal controls in all conditions, whereas non-proficient users showed significantly different audiovisual segregation patterns in both speech conditions. These results confirm that normal-like audiovisual segregation is possible in highly skilled cochlear implant users and, consequently, that proficient and non-proficient CI users cannot be lumped into a single group. This important feature must be taken into account in further studies of audiovisual interactions in cochlear implant users.

  12. Figure-ground segregation: A fully nonlocal approach.

    Science.gov (United States)

    Dimiccoli, Mariella

    2016-09-01

    We present a computational model that computes and integrates in a nonlocal fashion several configural cues for automatic figure-ground segregation. Our working hypothesis is that the figural status of each pixel is a nonlocal function of several geometric shape properties and it can be estimated without explicitly relying on object boundaries. The methodology is grounded on two elements: multi-directional linear voting and nonlinear diffusion. A first estimation of the figural status of each pixel is obtained as a result of a voting process, in which several differently oriented line-shaped neighborhoods vote to express their belief about the figural status of the pixel. A nonlinear diffusion process is then applied to enforce the coherence of figural status estimates among perceptually homogeneous regions. Computer simulations fit human perception and match the experimental evidence that several cues cooperate in defining figure-ground segregation. The results of this work suggest that figure-ground segregation involves feedback from cells with larger receptive fields in higher visual cortical areas. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Multigenerational Brazilian family with malignant hyperthermia and a novel mutation in the RYR1 gene.

    Science.gov (United States)

    Matos, A R; Sambuughin, N; Rumjanek, F D; Amoedo, N D; Cunha, L B P; Zapata-Sudo, G; Sudo, R T

    2009-12-01

    Malignant hyperthermia (MH) is a pharmacogenetic disease triggered in susceptible individuals by the administration of volatile halogenated anesthetics and/or succinylcholine, leading to the development of a hypermetabolic crisis, which is caused by abnormal release of Ca2+ from the sarcoplasmic reticulum, through the Ca2+ release channel ryanodine receptor 1 (RyR1). Mutations in the RYR1 gene are associated with MH in the majority of susceptible families. Genetic screening of a 5-generation Brazilian family with a history of MH-related deaths and a previous MH diagnosis by the caffeine halothane contracture test (CHCT) in some individuals was performed using restriction and sequencing analysis. A novel missense mutation, Gly4935Ser, was found in an important functional and conserved locus of this gene, the transmembrane region of RyR1. In this family, 2 MH-susceptible individuals previously diagnosed with CHCT carry this novel mutation and another 24 not previously diagnosed members also carry it. However, this same mutation was not found in another MH-susceptible individual whose CHCT was positive to the test with caffeine but not to the test with halothane. None of the 5 MH normal individuals of the family, previously diagnosed by CHCT, carry this mutation, nor do 100 controls from control Brazilian and USA populations. The Gly4932Ser variant is a candidate mutation for MH, based on its co-segregation with disease phenotype, absence among controls and its location within the protein.

  14. Figure-ground segregation can rely on differences in motion direction.

    Science.gov (United States)

    Kandil, Farid I; Fahle, Manfred

    2004-12-01

    If the elements within a figure move synchronously while those in the surround move at a different time, the figure is easily segregated from the surround and thus perceived. Lee and Blake (1999) [Visual form created solely from temporal structure. Science, 284, 1165-1168] demonstrated that this figure-ground separation may be based not only on time differences between motion onsets, but also on the differences between reversals of motion direction. However, Farid and Adelson (2001) [Synchrony does not promote grouping in temporally structured displays. Nature Neuroscience, 4, 875-876] argued that figure-ground segregation in the motion-reversal experiment might have been based on a contrast artefact and concluded that (a)synchrony as such was 'not responsible for the perception of form in these or earlier displays'. Here, we present experiments that avoid contrast artefacts but still produce figure-ground segregation based on purely temporal cues. Our results show that subjects can segregate figure from ground even though being unable to use motion reversals as such. Subjects detect the figure when either (i) motion stops (leading to contrast artefacts), or (ii) motion directions differ between figure and ground. Segregation requires minimum delays of about 15 ms. We argue that whatever the underlying cues and mechanisms, a second stage beyond motion detection is required to globally compare the outputs of local motion detectors and to segregate figure from ground. Since analogous changes take place in both figure and ground in rapid succession, this second stage has to detect the asynchrony with high temporal precision.

  15. Chromosomal organization and segregation in Pseudomonas aeruginosa.

    Directory of Open Access Journals (Sweden)

    Isabelle Vallet-Gely

    2013-05-01

    Full Text Available The study of chromosomal organization and segregation in a handful of bacteria has revealed surprising variety in the mechanisms mediating such fundamental processes. In this study, we further emphasized this diversity by revealing an original organization of the Pseudomonas aeruginosa chromosome. We analyzed the localization of 20 chromosomal markers and several components of the replication machinery in this important opportunistic γ-proteobacteria pathogen. This technique allowed us to show that the 6.3 Mb unique circular chromosome of P. aeruginosa is globally oriented from the old pole of the cell to the division plane/new pole along the oriC-dif axis. The replication machinery is positioned at mid-cell, and the chromosomal loci from oriC to dif are moved sequentially to mid-cell prior to replication. The two chromosomal copies are subsequently segregated at their final subcellular destination in the two halves of the cell. We identified two regions in which markers localize at similar positions, suggesting a bias in the distribution of chromosomal regions in the cell. The first region encompasses 1.4 Mb surrounding oriC, where loci are positioned around the 0.2/0.8 relative cell length upon segregation. The second region contains at least 800 kb surrounding dif, where loci show an extensive colocalization step following replication. We also showed that disrupting the ParABS system is very detrimental in P. aeruginosa. Possible mechanisms responsible for the coordinated chromosomal segregation process and for the presence of large distinctive regions are discussed.

  16. Sexual orientation, prejudice and segregation

    NARCIS (Netherlands)

    Plug, E.; Webbink, D.; Martin, N.

    2014-01-01

    This article examines whether gay and lesbian workers sort into tolerant occupations. With information on sexual orientation, prejudice, and occupational choice taken from Australian Twin Registers, we find that gays and lesbians shy away from prejudiced occupations. We show that our segregation

  17. Declining Segregation of Same-Sex Partners: Evidence from Census 2000 and 2010

    Science.gov (United States)

    2013-01-01

    Despite recent media and scholarly attention describing the “disappearance” of traditionally gay neighborhoods, urban scholars have yet to quantify the segregation of same-sex partners and determine whether declining segregation from different-sex partners is a wide-spread trend. Focusing on the 100 most populous places in the United States, I use data from the 2000 and 2010 Decennial Census to examine the segregation of same-sex partners over time and its place-level correlates. I estimate linear regression models to examine the role of four place characteristics in particular: average levels of education, aggregate trends in the family life cycle of same-sex partners, violence and social hostility motivated by sexual orientation bias, and representation of same-sex partners in the overall population. On average, same-sex partners were less segregated from different-sex partners in 2010 than in 2000, and the vast majority of same-sex partners lived in environments of declining segregation. Segregation was lower and declined more rapidly in places that had a greater percentage of graduate degree holders. In addition, segregation of female partners was lower in places that had a greater share of female partner households with children. These findings suggest that sexual orientation should be considered alongside economic status, race, and ethnicity as an important factor that contributes to neighborhood differentiation and urban spatial inequality. PMID:24187412

  18. Surface segregation of low-Z elements on plasma-facing materials

    International Nuclear Information System (INIS)

    Qian Jiapu; Liu Xiang

    1994-10-01

    Surface segregation behavior of low-Z elements, e.g., lithium and beryllium on ternary alloy Al-Li-Mg and Binary alloy Cu-Be has been observed. The experiments were performed by means of Secondary Ion Mass Spectroscopy (SIMS) and Auger Electron Spectroscopy (AEA). The experimental results of Al-Li-Mg alloy indicated that lithium concentration on the specimen surface reached approximately 100% in the temperature range of 150 to 300 degree C, which can be explained by Gibbsian segregation theory. The depth profile of Li showed that there was some broadening resulting from recoil implantation by high energy Ar ion bombardment. When the specimen temperature exceeded 360 degree C, beryllium, the impurity element in the alloy was found to segregate to the surface. For this reason, another experiment on surface segregation of Cu-Be alloy was carried out by SIMS and AES, the surface analysis utilizing in-situ AES analysis revealed that the surface was enriched by Be and O at elevated temperature, considering the chemical affinity of Be and O, the principal driving force of segregation was attributed to the oxygen partial pressure in the atmosphere. The depth profile of Be in the alloy was also investigated. (9 figs.)

  19. The Consequences of Chromosome Segregation Errors in Mitosis and Meiosis

    Directory of Open Access Journals (Sweden)

    Tamara Potapova

    2017-02-01

    Full Text Available Mistakes during cell division frequently generate changes in chromosome content, producing aneuploid or polyploid progeny cells. Polyploid cells may then undergo abnormal division to generate aneuploid cells. Chromosome segregation errors may also involve fragments of whole chromosomes. A major consequence of segregation defects is change in the relative dosage of products from genes located on the missegregated chromosomes. Abnormal expression of transcriptional regulators can also impact genes on the properly segregated chromosomes. The consequences of these perturbations in gene expression depend on the specific chromosomes affected and on the interplay of the aneuploid phenotype with the environment. Most often, these novel chromosome distributions are detrimental to the health and survival of the organism. However, in a changed environment, alterations in gene copy number may generate a more highly adapted phenotype. Chromosome segregation errors also have important implications in human health. They may promote drug resistance in pathogenic microorganisms. In cancer cells, they are a source for genetic and phenotypic variability that may select for populations with increased malignance and resistance to therapy. Lastly, chromosome segregation errors during gamete formation in meiosis are a primary cause of human birth defects and infertility. This review describes the consequences of mitotic and meiotic errors focusing on novel concepts and human health.

  20. Study of surface segregation of Si on palladium silicide using Auger electron spectroscopy

    International Nuclear Information System (INIS)

    Abhaya, S; Amarendra, G; Gopalan, Padma; Reddy, G L N; Saroja, S

    2004-01-01

    The transformation of Pd/Si to Pd 2 Si/Si is studied using Auger electron spectroscopy over a wide temperature range of 370-1020 K. The Pd film gets totally converted to Pd 2 Si upon annealing at 520 K, and beyond 570 K, Si starts segregating on the surface of silicide. It is found that the presence of surface oxygen influences the segregation of Si. The time evolution study of Si segregation reveals that segregation kinetics is very fast and the segregated Si concentration increases as the temperature is increased. Scanning electron microscopy measurements show that Pd 2 Si is formed in the form of islands, which grow as the annealing temperature is increased

  1. Electrophysiological correlates of purely temporal figure-ground segregation.

    Science.gov (United States)

    Kandil, Farid I; Fahle, Manfred

    2003-11-01

    Inhomogenous displays, in contrast to homogenous ones, evoke a specific potential in the VEP (tsVEP) which appears across different classical visual stimulus dimensions defining figure-ground segregation, such as luminance, orientation, (first-order) motion, and stereoscopic depth. This negative potential has a peak latency of about 200-300 ms and a peak amplitude of about -3 to -10 microV [Doc Ophthalmol. 95 (1998) 335]. Previously, we demonstrated that human subjects reliably segregate figure from ground, even in the absence of the classical cues, leaving time of change as the only cue for segregation. The results of the present study demonstrate that also purely temporally defined checkerboards evoke a tsVEP resembling the motion-defined tsVEP regarding polarity (negative), latency (two peaks at 180 and 270 ms, respectively), amplitude of the first negativity (-5.6 microV), and overall form of its components.

  2. Atomic scale study of grain boundary segregation before carbide nucleation in Ni–Cr–Fe Alloys

    Energy Technology Data Exchange (ETDEWEB)

    Li, Hui, E-mail: huili@shu.edu.cn [Key Laboratory for Microstructures, Shanghai University, Shanghai 200444 (China); Institute of Materials, Shanghai University, Shanghai 200072 (China); Xia, Shuang [Institute of Materials, Shanghai University, Shanghai 200072 (China); Liu, Wenqing [Key Laboratory for Microstructures, Shanghai University, Shanghai 200444 (China); Liu, Tingguang; Zhou, Bangxin [Institute of Materials, Shanghai University, Shanghai 200072 (China)

    2013-08-15

    Highlights: • Impurities segregated at grain boundaries were observed by atom probe tomography. • The comparison of segregation features in two Ni–Cr–Fe alloys was studied by APT. • C and Cr atoms co-segregated at grain boundaries before carbide precipitation. -- Abstract: Three dimensional chemical information concerning grain boundary segregation before carbide nucleation was characterized by atom probe tomography in two Ni–Cr–Fe alloys which were aged at 500 °C for 0.5 h after homogenizing treatment. B, C and Si atoms segregation at grain boundary in Alloy 690 was observed. B, C, N and P atoms segregation at grain boundary in 304 austenitic stainless steel was observed. C atoms co-segregation with Cr atoms at the grain boundaries both in Alloy 690 and 304 austenitic stainless steel was found, and its effect on the carbide nucleation was discussed. The amount of each segregated element at grain boundaries in the two Ni–Cr–Fe alloys were analyzed quantitatively. Comparison of the grain boundary segregation features of the two Ni–Cr–Fe alloys were carried out based on the experimental results.

  3. Atomic-scale investigations of grain boundary segregation in astrology with a three dimensional atom-probe

    Energy Technology Data Exchange (ETDEWEB)

    Blavette, D. [Rouen Univ., 76 - Mont-Saint-Aignan (France). Lab. de Microscopie Electronique]|[Institut Universitaire de France (France); Letellier, L. [Rouen Univ., 76 - Mont-Saint-Aignan (France). Lab. de Microscopie Electronique; Duval, P. [Rouen Univ., 76 - Mont-Saint-Aignan (France). Lab. de Microscopie Electronique; Guttmann, M. [Rouen Univ., 76 - Mont-Saint-Aignan (France). Lab. de Microscopie Electronique]|[Institut de Recherches de la Siderurgie Francaise (IRSID), 57 - Maizieres-les-Metz (France)

    1996-08-01

    Both conventional and 3D atom-probes were applied to the investigation of grain-boundary (GB) segregation phenomena in two-phase nickel base superalloys Astroloy. 3D images as provided by the tomographic atom-probe reveal the presence of a strong segregation of both boron and molybdenum at grain-boundaries. Slight carbon enrichment is also detected. Considerable chromium segregation is exhibited at {gamma}`-{gamma}` grain-boundaries. All these segregants are distributed in a continuous manner along the boundary over a width close to 0.5 nm. Experiments show that segregation occurs during cooling and more probably between 1000 C and 800 C. Boron and molybdenum GB enrichments are interpreted as due to an equilibrium type-segregation while chromium segregation is thought to be induced by {gamma}` precipitation at GB`s and stabilised by the presence of boron. No segregation of zirconium is detected. (orig.)

  4. Strand-seq : A unifying tool for studies of chromosome segregation

    NARCIS (Netherlands)

    Falconer, Ester; Lansdorp, Peter M.

    2013-01-01

    Non random segregation of sister chromatids has been implicated to help specify daughter cell fate (the Silent Sister Hypothesis [1]) or to protect the genome of long-lived stem cells (the Immortal Strand Hypothesis [2]). The idea that sister chromatids are non-randomly segregated into specific

  5. Segregation effects in welded stainless steels

    International Nuclear Information System (INIS)

    Akhter, J.I.; Shoaid, K.A.; Ahmed, M.; Malik, A.Q.

    1987-01-01

    Welding of steels causes changes in the microstructure and chemical composition which could adversely affect the mechanical and corrosion properties. The report describes the experimental results of an investigation of segregation effects in welded austenitic stainless steels of AISI type 304, 304L, 316 and 316L using the techniques of scanning electron microscopy and electron probe microanalysis. Considerable enhancement of chromium and carbon has been observed in certain well-defined zones on the parent metal and on composition, particularly in the parent metal, in attributed to the formation of (M 23 C 6 ) precipitates. The formation of geometrically well-defined segregation zones is explained on the basis of the time-temperature-precipitation curve of (M 23 C 6 ). (author)

  6. Non-uniform Solute Segregation at Semi-Coherent Metal/Oxide Interfaces

    Science.gov (United States)

    Choudhury, Samrat; Aguiar, Jeffery A.; Fluss, Michael J.; Hsiung, Luke L.; Misra, Amit; Uberuaga, Blas P.

    2015-08-01

    The properties and performance of metal/oxide nanocomposites are governed by the structure and chemistry of the metal/oxide interfaces. Here we report an integrated theoretical and experimental study examining the role of interfacial structure, particularly misfit dislocations, on solute segregation at a metal/oxide interface. We find that the local oxygen environment, which varies significantly between the misfit dislocations and the coherent terraces, dictates the segregation tendency of solutes to the interface. Depending on the nature of the solute and local oxygen content, segregation to misfit dislocations can change from attraction to repulsion, revealing the complex interplay between chemistry and structure at metal/oxide interfaces. These findings indicate that the solute chemistry at misfit dislocations is controlled by the dislocation density and oxygen content. Fundamental thermodynamic concepts - the Hume-Rothery rules and the Ellingham diagram - qualitatively predict the segregation behavior of solutes to such interfaces, providing design rules for novel interfacial chemistries.

  7. Multi-way multi-group segregation and diversity indices.

    Science.gov (United States)

    Gorelick, Root; Bertram, Susan M

    2010-06-01

    How can we compute a segregation or diversity index from a three-way or multi-way contingency table, where each variable can take on an arbitrary finite number of values and where the index takes values between zero and one? Previous methods only exist for two-way contingency tables or dichotomous variables. A prototypical three-way case is the segregation index of a set of industries or departments given multiple explanatory variables of both sex and race. This can be further extended to other variables, such as disability, number of years of education, and former military service. We extend existing segregation indices based on Euclidean distance (square of coefficient of variation) and Boltzmann/Shannon/Theil index from two-way to multi-way contingency tables by including multiple summations. We provide several biological applications, such as indices for age polyethism and linkage disequilibrium. We also provide a new heuristic conceptualization of entropy-based indices. Higher order association measures are often independent of lower order ones, hence an overall segregation or diversity index should be the arithmetic mean of the normalized association measures at all orders. These methods are applicable when individuals self-identify as multiple races or even multiple sexes and when individuals work part-time in multiple industries. The policy implications of this work are enormous, allowing people to rigorously test whether employment or biological diversity has changed.

  8. Two critical periods in early visual cortex during figure–ground segregation

    OpenAIRE

    Wokke, Martijn E; Sligte, Ilja G; Steven Scholte, H; Lamme, Victor A F

    2012-01-01

    .The ability to distinguish a figure from its background is crucial for visual perception. To date, it remains unresolved where and how in the visual system different stages of figure-ground segregation emerge. Neural correlates of figure border detection have consistently been found in early visual cortex (V1/V2). However, areas V1/V2 have also been frequently associated with later stages of figure-ground segregation (such as border ownership or surface segregation). To causally link activit...

  9. The endoplasmic reticulum is a hub to sort proteins toward unconventional traffic pathways and endosymbiotic organelles.

    Science.gov (United States)

    Bellucci, Michele; De Marchis, Francesca; Pompa, Andrea

    2017-12-18

    The discovery that much of the extracellular proteome in eukaryotic cells consists of proteins lacking a signal peptide, which cannot therefore enter the secretory pathway, has led to the identification of alternative protein secretion routes bypassing the Golgi apparatus. However, proteins harboring a signal peptide for translocation into the endoplasmic reticulum can also be transported along these alternative routes, which are still far from being well elucidated in terms of the molecular machineries and subcellular/intermediate compartments involved. In this review, we first try to provide a definition of all the unconventional protein secretion pathways in eukaryotic cells, as those pathways followed by proteins directed to an 'external space' bypassing the Golgi, where 'external space' refers to the extracellular space plus the lumen of the secretory route compartments and the inner space of mitochondria and plastids. Then, we discuss the role of the endoplasmic reticulum in sorting proteins toward unconventional traffic pathways in plants. In this regard, various unconventional pathways exporting proteins from the endoplasmic reticulum to the vacuole, plasma membrane, apoplast, mitochondria, and plastids are described, including the short routes followed by the proteins resident in the endoplasmic reticulum. © The Author(s) 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  10. Residential segregation and overweight/obesity among African-American adults: A critical review

    Directory of Open Access Journals (Sweden)

    Irma eCorral

    2015-07-01

    Full Text Available The relationship between residential segregation and overweight/obesity among African-American adults remains unclear. Elucidating that relationship is relevant to efforts to prevent and to reduce racial disparities in obesity. This article provides a critical review of the 11 empirical studies of segregation and overweight/obesity among African-American adults. Results revealed that most studies did not use a valid measure of segregation, many did not use a valid measure of overweight/obesity, and many did not control for neighborhood poverty. Only four (36% of the studies used valid measures of both segregation and overweight/obesity and also controlled for area-poverty. Those four studies suggest that segregation contributes to overweight and obesity among African-American adults, but that conclusion cannot be drawn with any certainty in light of the considerable methodological problems in this area of research. Suggestions for improving research on this topic are provided.

  11. Do measures matter? Comparing surface-density-derived and census-tract-derived measures of racial residential segregation

    Directory of Open Access Journals (Sweden)

    Waller Lance A

    2010-06-01

    Full Text Available Abstract Background Racial residential segregation is hypothesized to affect population health by systematically patterning health-relevant exposures and opportunities according to individuals' race or income. Growing interest into the association between residential segregation and health disparities demands more rigorous appraisal of commonly used measures of segregation. Most current studies rely on census tracts as approximations of the local residential environment when calculating segregation indices of either neighborhoods or metropolitan areas. Because census tracts are arbitrary in size and shape, reliance on this geographic scale limits understanding of place-health associations. More flexible, explicitly spatial derivations of traditional segregation indices have been proposed but have not been compared with tract-derived measures in the context of health disparities studies common to social epidemiology, health demography, or medical geography. We compared segregation measured with tract-derived as well as GIS surface-density-derived indices. Measures were compared by region and population size, and segregation measures were linked to birth record to estimate the difference in association between segregation and very preterm birth. Separate analyses focus on metropolitan segregation and on neighborhood segregation. Results Across 231 metropolitan areas, tract-derived and surface-density-derived segregation measures are highly correlated. However overall correlation obscures important differences by region and metropolitan size. In general the discrepancy between measure types is greatest for small metropolitan areas, declining with increasing population size. Discrepancies in measures are greatest in the South, and smallest in Western metropolitan areas. Choice of segregation index changed the magnitude of the measured association between segregation and very preterm birth. For example among black women, the risk ratio for very

  12. Influence of segregations and hydrogen flakes on the mechanical properties of forged RPV steels

    International Nuclear Information System (INIS)

    Eiselt, C.C.; May, J.; Hein, H.

    2013-01-01

    In the frame of relevant 1970s/80s German research programs (e.g. FKS research program on component safety and others), many investigations on large forgings manufactured from Reactor Pressure Vessel (RPV) materials such as 20 MnMoNi 5 5 and 22 NiMoCr 3 7 have been performed. Lately, after ultrasonic testing hydrogen flakes in connection with segregation zones have been observed in a few RPV forgings. The earlier R and D programs contained a number of special heats, which covered a defined defect state (lower bound heats) with relevance to the recent observations of numerous UT indications in RPV forgings of two PWRs. Therefore, the results of these former research programs were now reviewed. The studies included an evaluation of the effects of macro/micro segregations as well as hydrogen flakes on the mechanical properties. As part of the mechanical technological experiments Charpy impact tests in different orientations (e.g. L-T, T-L and S-T) together with fracture mechanics and large scale tensile tests were carried out in segregated and non segregated material zones. In this context the letters L,T,S indicate the longitudinal, transversal and short transverse (thickness) direction with respect to rolling direction of the forging axis. The first letter indicates the direction of the principal stress, while the second letter stands for the crack propagation direction [1]. Furthermore the irradiation behavior of segregated material regions was analyzed and compared to non segregated material regions. Key results of these analyses indicate that in most cases upper shelf levels are lowered in segregated material parts compared to non segregated areas. In addition the segregations cause a larger scattering of impact energies. A high hydrogen content in combination with segregations has overall detrimental effects on the mechanical properties. However, there seems to be no specific segregation influence on the materials' irradiation reaction.

  13. Seeing Race: Teaching Residential Segregation with the Racial Dot Map

    Science.gov (United States)

    Seguin, Charles; Nierobisz, Annette; Kozlowski, Karen Phelan

    2017-01-01

    Students commonly hold erroneous notions of a "post-racial" world and individualistic worldviews that discount the role of structure in social outcomes. Jointly, these two preconceived beliefs can be powerful barriers to effective teaching of racial segregation: Students may be skeptical that racial segregation continues to exist, and…

  14. Spatial Reorganization of the Endoplasmic Reticulum during Mitosis Relies on Mitotic Kinase Cyclin A in the Early Drosophila Embryo

    Science.gov (United States)

    Bergman, Zane J.; Mclaurin, Justin D.; Eritano, Anthony S.; Johnson, Brittany M.; Sims, Amanda Q.; Riggs, Blake

    2015-01-01

    Mitotic cyclin-dependent kinase with their cyclin partners (cyclin:Cdks) are the master regulators of cell cycle progression responsible for regulating a host of activities during mitosis. Nuclear mitotic events, including chromosome condensation and segregation have been directly linked to Cdk activity. However, the regulation and timing of cytoplasmic mitotic events by cyclin:Cdks is poorly understood. In order to examine these mitotic cytoplasmic events, we looked at the dramatic changes in the endoplasmic reticulum (ER) during mitosis in the early Drosophila embryo. The dynamic changes of the ER can be arrested in an interphase state by inhibition of either DNA or protein synthesis. Here we show that this block can be alleviated by micro-injection of Cyclin A (CycA) in which defined mitotic ER clusters gathered at the spindle poles. Conversely, micro-injection of Cyclin B (CycB) did not affect spatial reorganization of the ER, suggesting CycA possesses the ability to initiate mitotic ER events in the cytoplasm. Additionally, RNAi-mediated simultaneous inhibition of all 3 mitotic cyclins (A, B and B3) blocked spatial reorganization of the ER. Our results suggest that mitotic ER reorganization events rely on CycA and that control and timing of nuclear and cytoplasmic events during mitosis may be defined by release of CycA from the nucleus as a consequence of breakdown of the nuclear envelope. PMID:25689737

  15. Residential segregation and public policies: São Paulo in the 1990's

    Directory of Open Access Journals (Sweden)

    Haroldo da Gama Torres

    2006-01-01

    Full Text Available The article aims at assessing the evolution of residential segregation in the metropolitan area of São Paulo, Brazil, in the 1990's, which saw a significant increase of socioeconomic segregation. In addition to interpreting the phenomenon, the article proposes a discussion on the reasons the residential segregation should be considered a fundamental issue for the formulation of social urban policies.

  16. A Framework for Music-Speech Segregation using Music Fingerprinting and Acoustic Echo Cancellation Principle

    International Nuclear Information System (INIS)

    Hussain, F.; Habib, H. A.; Khan, M. J.

    2015-01-01

    Background interference creates voice intelligibility issue for listerner. This research work considers background music as interference for communication through smart phone in areas with loud background music. This paper proposes a novel framework for background music segregation from human speech using music fingerprinting and acoustic echo cancellation. Initially, background music is searched in the database by music fingerprinting. Identified background music is registered and segregated using acoustic echo cancellation. Proposed approach generates better quality music speech segregation than existing algorithms. The research work is novel and segregates background music completely in comparison to existing approaches where single instruments are segregated successfully. (author)

  17. Sch proteins are localized on endoplasmic reticulum membranes and are redistributed after tyrosine kinase receptor activation

    DEFF Research Database (Denmark)

    Lotti, L V; Lanfrancone, L; Migliaccio, E

    1996-01-01

    area of the cell and mostly associated with the cytosolic side of rough endoplasmic reticulum membranes. Upon epidermal growth factor treatment and receptor tyrosine kinase activation, the immunolabeling became peripheral and was found to be associated with the cytosolic surface of the plasma membrane....... The rough endoplasmic reticulum localization of Shc proteins in unstimulated cells and their massive recruitment to the plasma membrane, endocytic structures, and peripheral cytosol following receptor tyrosine kinase activation could account for multiple putative functions of the adaptor protein....

  18. Left ventricular wall stress and sarcoplasmic reticulum Ca(2+)-ATPase gene expression in renal hypertensive rats: dose-dependent effects of ACE inhibition and AT1-receptor blockade.

    Science.gov (United States)

    Zierhut, W; Studer, R; Laurent, D; Kästner, S; Allegrini, P; Whitebread, S; Cumin, F; Baum, H P; de Gasparo, M; Drexler, H

    1996-05-01

    Cardiac hypertrophy is associated with altered Ca2+ handling and may predispose to the development of LV dysfunction and cardiac failure. At the cellular level, the re-expression of ANF represents a well-established marker of myocyte hypertrophy while the decreased expression of the sarcoplasmatic reticulum (SR) Ca(2+)-ATPase is thought o play a crucial role in the alterations of Ca2+ handling and LV function. We assessed the dose-dependent effect of chronic ACE inhibition or AT1 receptor blockade on cardiac function in relation to the cardiac expression of the SR Ca(2+)-ATPase and ANF. Renal hypertensive rats (2K-1C) were treated for 12 weeks with three different doses of the ACE inhibitor benazepril, the AT1-receptor antagonist valsartan (each drug 0.3, 3, and 10 mg/kg per day i.p.) or placebo. LV dimensions, hypertrophy and wall stress were determined in vivo by magnetic resonance imaging and the gene expressions of ANF and SR Ca(2+)-ATPase were quantified by Northern blot. Low doses of both drugs did not affect blood pressure, hypertrophy, systolic wall stress and the ANF and SR Ca(2+)-ATPase gene expression. High doses of each drug reduced systolic blood pressure, wall stress, and LV hypertrophy to a similar extent and to values comparable to normotensive, age-matched rats. In addition, high dose treatment reduced LV end-systolic and end-diastolic volume as compared to untreated 2K-1C animals and normalized the mRNA levels of both ANF and SR Ca(2+)-ATPase (as compared to normotensive animals). We conclude that in this model, high doses of ACE inhibition and AT1-receptor blockade are necessary to normalize systolic blood pressure, LV hypertrophy and systolic LV wall stress which, in turn, is associated with restoration of a normal cardiac phenotype with respect to SR Ca(2+)-ATPase and ANF and normalization of cardiac function.

  19. Cytoskeletal-assisted dynamics of the mitochondrial reticulum in living cells.

    Science.gov (United States)

    Knowles, Michelle K; Guenza, Marina G; Capaldi, Roderick A; Marcus, Andrew H

    2002-11-12

    Subcellular organelle dynamics are strongly influenced by interactions with cytoskeletal filaments and their associated motor proteins, and lead to complex multiexponential relaxations that occur over a wide range of spatial and temporal scales. Here we report spatio-temporal measurements of the fluctuations of the mitochondrial reticulum in osteosarcoma cells by using Fourier imaging correlation spectroscopy, over time and distance scales of 10(-2) to 10(3) s and 0.5-2.5 microm. We show that the method allows a more complete description of mitochondrial dynamics, through the time- and length-scale-dependent collective diffusion coefficient D(k,tau), than available by other means. Addition of either nocodazole to disrupt microtubules or cytochalasin D to disassemble microfilaments simplifies the intermediate scattering function. When both drugs are used, the reticulum morphology of mitochondria is retained even though the cytoskeletal elements have been de-polymerized. The dynamics of the organelle are then primarily diffusive and can be modeled as a collection of friction points interconnected by elastic springs. This study quantitatively characterizes organelle dynamics in terms of collective cytoskeletal interactions in living cells.

  20. Successful Implementation of Soil Segregation Technology at the Painesville FUSRAP Site - 12281

    Energy Technology Data Exchange (ETDEWEB)

    Buechi, Stephen P.; Andrews, Shawn M. [U.S. Army Corps of Engineers, Buffalo District, Buffalo, New York (United States); Lombardo, Andrew J. [Safety and Ecology Corporation, Beaver, Pennsylvania (United States); Lively, Jeffrey W. [AMEC Environment and Infrastructure, Grand Junction, Colorado (United States)

    2012-07-01

    Typically the highest cost component of the radiological soils remediation of Formerly Utilized Sites Remedial Action Program (FUSRAP) sites is the cost to transport and dispose of the excavated soils, typically contaminated with naturally occurring isotopes of uranium, thorium and radium, at an appropriately permitted off-site disposal facility. The heterogeneous nature of the contamination encountered at these sites makes it difficult to accurately delineate the extent of contaminated soil using the limited, discrete sampling data collected during the investigation phases; and difficult to precisely excavate only the contaminated soil that is above the established cleanup limits using standard in-field scanning and guiding methodologies. This usually results in a conservative guided excavation to ensure cleanup criteria are met, with the attendant transportation and disposal costs for the larger volumes of soil excavated. To address this issue during the remediation of the Painesville FUSRAP Site, located in Painesville, Ohio, the Buffalo District of the U.S. Army Corps of Engineers, and its contractor, Safety and Ecology Corporation (SEC), employed automatic soil segregation technology provided by MACTEC (now AMEC) to reduce the potential for transportation and disposal of soils that met the cleanup limits. This waste minimization technology utilized gamma spectroscopy of conveyor-fed soils to automatically segregate the material into above and below criteria discharge piles. Use of the soil segregation system resulted in cost savings through the significant reduction of the volume of excavated soil that required off-site transportation and disposal, and the reduction of the amount of imported clean backfill required via reuse of 'below criteria' segregated soil as place back material in restoring the excavations. Measurements taken by the soil segregation system, as well as results of quality control sampling of segregated soils, confirmed that soils

  1. Figure-ground segregation in a recurrent network architecture.

    Science.gov (United States)

    Roelfsema, Pieter R; Lamme, Victor A F; Spekreijse, Henk; Bosch, Holger

    2002-05-15

    Here we propose a model of how the visual brain segregates textured scenes into figures and background. During texture segregation, locations where the properties of texture elements change abruptly are assigned to boundaries, whereas image regions that are relatively homogeneous are grouped together. Boundary detection and grouping of image regions require different connection schemes, which are accommodated in a single network architecture by implementing them in different layers. As a result, all units carry signals related to boundary detection as well as grouping of image regions, in accordance with cortical physiology. Boundaries yield an early enhancement of network responses, but at a later point, an entire figural region is grouped together, because units that respond to it are labeled with enhanced activity. The model predicts which image regions are preferentially perceived as figure or as background and reproduces the spatio-temporal profile of neuronal activity in the visual cortex during texture segregation in intact animals, as well as in animals with cortical lesions.

  2. Segregation 2.0: The New Generation of School Segregation in the 21st Century

    Science.gov (United States)

    Thompson Dorsey, Dana N.

    2013-01-01

    Students are more racially segregated in schools today than they were in the late 1960s and prior to the enforcement of court-ordered desegregation in school districts across the country. This special issue addresses the overarching theme of policies, practices, or roles and responsibilities of various stakeholders that may directly or indirectly…

  3. Role of glycogen availability in sarcoplasmic reticulum Ca2+ kinetics in human skeletal muscle

    DEFF Research Database (Denmark)

    Ørtenblad, Niels; Nielsen, Joachim; Saltin, Bengt

    2011-01-01

    Glucose is stored as glycogen in skeletal muscle. The importance of glycogen as a fuel during exercise has been recognized since the 1960s; however, little is known about the precise mechanism that relates skeletal muscle glycogen to muscle fatigue. We show that low muscle glycogen is associated...... with an impairment of muscle ability to release Ca(2+), which is an important signal in the muscle activation. Thus, depletion of glycogen during prolonged, exhausting exercise may contribute to muscle fatigue by causing decreased Ca(2+) release inside the muscle. These data provide indications of a signal...

  4. Integration and segregation in auditory scene analysis

    Science.gov (United States)

    Sussman, Elyse S.

    2005-03-01

    Assessment of the neural correlates of auditory scene analysis, using an index of sound change detection that does not require the listener to attend to the sounds [a component of event-related brain potentials called the mismatch negativity (MMN)], has previously demonstrated that segregation processes can occur without attention focused on the sounds and that within-stream contextual factors influence how sound elements are integrated and represented in auditory memory. The current study investigated the relationship between the segregation and integration processes when they were called upon to function together. The pattern of MMN results showed that the integration of sound elements within a sound stream occurred after the segregation of sounds into independent streams and, further, that the individual streams were subject to contextual effects. These results are consistent with a view of auditory processing that suggests that the auditory scene is rapidly organized into distinct streams and the integration of sequential elements to perceptual units takes place on the already formed streams. This would allow for the flexibility required to identify changing within-stream sound patterns, needed to appreciate music or comprehend speech..

  5. Radiation-induced segregation behavior in random and ordered face-centered cubic materials

    International Nuclear Information System (INIS)

    Bui, T.X.; Robertson, I.M.; Klatt, J.L.; Averback, R.S.; Kirk, M.A.

    1993-01-01

    Radiation-induced segregation has been studied in random solid solution alloys Ni-10%Al and Ni-6%Si, and in the ordered (L1 2 structure) intermetallics Ni 3 Si and Ni 3 Al. These materials were irradiated with 2 MeV He + ions at a temperature between 0.45 and 0.55T m and at an ion dose rate of approximately 1x10 -4 dpa per second. Subsequent Auger Electron Spectroscopy analysis showed that silicon segregated to the surface in the Ni-6% Si and Ni 3 Si alloys, and aluminum segregated away from the near surface region in the Ni-10% Al alloy. The Ni 3 Al samples exhibited no detectable segregation with respect to depth from the sample surface. The mechanisms that may give rise to this resistance to radiation induced segregation will be examined in terms of the mobility of the alloying constituents, ordering energies and atomic sizes. (orig.)

  6. Grain size segregation in debris discs

    Science.gov (United States)

    Thebault, P.; Kral, Q.; Augereau, J.-C.

    2014-01-01

    Context. In most debris discs, dust grain dynamics is strongly affected by stellar radiation pressure. Because this mechanism is size-dependent, we expect dust grains to be spatially segregated according to their sizes. However, because of the complex interplay between radiation pressure, grain processing by collisions, and dynamical perturbations, this spatial segregation of the particle size distribution (PSD) has proven difficult to investigate and quantify with numerical models. Aims: We propose to thoroughly investigate this problem by using a new-generation code that can handle some of the complex coupling between dynamical and collisional effects. We intend to explore how PSDs behave in both unperturbed discs at rest and in discs pertubed by planetary objects. Methods: We used the DyCoSS code to investigate the coupled effect of collisions, radiation pressure, and dynamical perturbations in systems that have reached a steady-state. We considered two setups: a narrow ring perturbed by an exterior planet, and an extended disc into which a planet is embedded. For both setups we considered an additional unperturbed case without a planet. We also investigated the effect of possible spatial size segregation on disc images at different wavelengths. Results: We find that PSDs are always spatially segregated. The only case for which the PSD follows a standard dn ∝ s-3.5ds law is for an unperturbed narrow ring, but only within the parent-body ring itself. For all other configurations, the size distributions can strongly depart from such power laws and have steep spatial gradients. As an example, the geometrical cross-section of the disc is very rarely dominated by the smallest grains on bound orbits, as it is expected to be in standard PSDs in sq with q ≤ -3. Although the exact profiles and spatial variations of PSDs are a complex function of the set-up that is considered, we are still able to derive some reliable results that will be useful for image or SED

  7. Evolutionary dynamics of adult stem cells: comparison of random and immortal-strand segregation mechanisms.

    Science.gov (United States)

    Tannenbaum, Emmanuel; Sherley, James L; Shakhnovich, Eugene I

    2005-04-01

    This paper develops a point-mutation model describing the evolutionary dynamics of a population of adult stem cells. Such a model may prove useful for quantitative studies of tissue aging and the emergence of cancer. We consider two modes of chromosome segregation: (1) random segregation, where the daughter chromosomes of a given parent chromosome segregate randomly into the stem cell and its differentiating sister cell and (2) "immortal DNA strand" co-segregation, for which the stem cell retains the daughter chromosomes with the oldest parent strands. Immortal strand co-segregation is a mechanism, originally proposed by [Cairns Nature (London) 255, 197 (1975)], by which stem cells preserve the integrity of their genomes. For random segregation, we develop an ordered strand pair formulation of the dynamics, analogous to the ordered strand pair formalism developed for quasispecies dynamics involving semiconservative replication with imperfect lesion repair (in this context, lesion repair is taken to mean repair of postreplication base-pair mismatches). Interestingly, a similar formulation is possible with immortal strand co-segregation, despite the fact that this segregation mechanism is age dependent. From our model we are able to mathematically show that, when lesion repair is imperfect, then immortal strand co-segregation leads to better preservation of the stem cell lineage than random chromosome segregation. Furthermore, our model allows us to estimate the optimal lesion repair efficiency for preserving an adult stem cell population for a given period of time. For human stem cells, we obtain that mispaired bases still present after replication and cell division should be left untouched, to avoid potentially fixing a mutation in both DNA strands.

  8. Cost-benefit analysis for waste segregation at Lawrence Livermore National Laboratory

    International Nuclear Information System (INIS)

    1992-02-01

    This report presents a cost-benefit analysis for the segregation of mixed, hazardous, and nonhazardous wastes at Lawrence Livermore National Laboratory (LLNL). The cost-benefit analysis was conducted to determine if current waste segregation practices and additional candidates for waste segregation at LLNL might have the potential for significant waste source reduction and annual savings in treatment and disposal costs. In the following cost-benefit analysis, capital costs and recurring costs of waste segregation practices are compared to the economic benefits of savings in treatment and disposal costs. Indirect or overhead costs associated with these wastes are not available and have not been included. Not considered are additional benefits of waste segregation such as decreased potential for liability to LLNL for adverse environmental effects, improved worker safety, and enhanced LLNL image within the community because of environmental improvement. The economic evaluations in this report are presented on a Lab-wide basis. All hazardous wastes generated by a program are turned over to the Hazardous Waste Management (HWM) group, which is responsible for the storage, treatment, or disposal of these wastes and funded funded directly for this work

  9. Caspase-12 is involved in stretch-induced apoptosis mediated endoplasmic reticulum stress.

    Science.gov (United States)

    Zhang, Qiang; Liu, Jianing; Chen, Shulan; Liu, Jing; Liu, Lijuan; Liu, Guirong; Wang, Fang; Jiang, Wenxin; Zhang, Caixia; Wang, Shuangyu; Yuan, Xiao

    2016-04-01

    It is well recognized that mandibular growth, which is caused by a variety of functional appliances, is considered to be the result of both neuromuscular and skeletal adaptations. Accumulating evidence has demonstrated that apoptosis plays an important role in the adaptation of skeletal muscle function. However, the underlying mechanism of apoptosis that is induced by stretch continues to be incompletely understood. Endoplasmic reticulum stress (ERS), a newly defined signaling pathway, initiates apoptosis. This study seeks to determine if caspase-12 is involved in stretch-induced apoptosis mediated endoplasmic reticulum stress in myoblast and its underlying mechanism. Apoptosis was assessed by Hochest staining, DAPI staining and annexin V binding and PI staining. ER chaperones, such as GRP78, CHOP and caspase-12, were determined by reverse transcription polymerase chain reaction (RT-PCR) and Western blot. Furthermore, caspase-12 inhibitor was used to value the mechanism of the caspase-12 pathway. Apoptosis of myoblast, which is subjected to cyclic stretch, was observed in a time-dependent manner. We found that GRP78 mRNA and protein were significantly increased and CHOP and caspase-12 were activated in myoblast that was exposed to cyclic stretch. Caspase-12 inhibition reduced stretch-induced apoptosis, and caspase-12 activated caspase-3 to induce apoptosis. We concluded that caspase-12 played an important role in stretch-induced apoptosis that is associated by endoplasmic reticulum stress by activating caspase-3.

  10. Dose dependence of radiation-induced segregation in Ni-1 at% Si

    International Nuclear Information System (INIS)

    Rehn, L.E.; Okamoto, P.R.; Wiedersich, H.

    1979-01-01

    Measurements have been made of alloy composition as a function of depth from the external surface in Ni-1 at% Si specimens after irradiation with 3-MeV 58 Ni + ions to several different doses at nominal temperatures of 525 and 600 0 C. Very rapid segregation of Si toward the external surface ocurred during irradiation. Surface concentrations of Si in excess of the 10 at% solubility limit were found at both irradiation temperatures after a dose of only approximately 0.05 dpa. The rate of segregation decreased markedly in the dose range from approximately 1-10 dpa. Qualitative agreement was found between the experimental observations and calculations made using a modified Johnson-Lam segregation mode (1976). The present investigation suggests that radiation-induced segregation may significantly alter the mechanical behavior of irradiated alloys long before the onset of void swelling. (Auth.)

  11. Thermodynamic and Kinetic Modeling on Thermal Segregation of Phosphorus in Iron

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Ying [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2016-03-01

    Radiation induced segregation (RIS) has been frequently reported in structural materials such as austenitic, ferritic, and ferritic-martensitic stainless steels (SS) that have been widely used in light water reactors (LWRs). RIS has been linked to secondary degradation effects in SS including irradiation induced stress corrosion cracking (IASCC). Earlier studies on thermal segregation in Fe based alloys found that metalloids elements such as P, S, Si, Ge, Sn etc. embrittle the materials when enrichment was observed at grain boundaries. RIS of Fe-Cr-Ni based austenitic steels has been modeled in the U.S. 2015 fiscal year (FY2015), which identified the pre-enrichment due to thermal segregation can have an important role on the subsequent RIS. The goal of this work is to develop thermal segregation models for alloying elements in steels for future integration with RIS modeling.

  12. Gibbsian and radiation-induced segregation in Cu--Li and Al--Li alloys

    International Nuclear Information System (INIS)

    Gruen, D.M.; Krauss, A.R.; Susman, S.; Venugopalan, M.; Ron, M.

    1983-01-01

    Previous experiments on segregation in dilute alloys of lithium in aluminum have demonstrated rapid enrichment of lithium in the uppermost monolayer, as well as a slower buildup in the subsurface region as a result of radiation-induced segregation effects during sputtering. Surface and subsurface enrichment of lithium in copper and aluminum alloys has been observed by secondary ion mass spectroscopy (SIMS), Auger electron spectroscopy (AES), and x-ray photoemission spectroscopy (XPS). The activation energies for lithium diffusion in Cu and Al have been measured and segregation kinetics are compared for dilute alloys of Li in Cu and Al, and a high lithium content copper alloy. The results are interpreted in terms of both Gibbsian and radiation-induced segregation effects

  13. New Jersey's Segregated Schools: Trends and Paths Forward

    Science.gov (United States)

    Orfield, Gary; Ee, Jongyeon; Coughlan, Ryan

    2017-01-01

    This report updates earlier research published by the Civil Rights Project in 2013. That report detailed troubling racial and economic segregation trends and patterns from 1989-2010. The latest report includes new data from 2010-2015. The research updates public school enrollment trends and details segregation in the state's schools by race and…

  14. "Brown" at 62: School Segregation by Race, Poverty and State

    Science.gov (United States)

    Orfield, Gary; Ee, Jongyeon; Frankenberg, Erica; Siegel-Hawley, Genevieve

    2016-01-01

    As the anniversary of "Brown v. Board of Education" decision arrives again without any major initiatives to mitigate spreading and deepening segregation in the nation's schools, the Civil Rights Project adds to a growing national discussion with a research brief drawn from a much broader study of school segregation to be published in…

  15. Phase Segregation in Polystyrene?Polylactide Blends

    Energy Technology Data Exchange (ETDEWEB)

    Leung, Bonnie; Hitchcock, Adam; Brash, John; Scholl, Andreas; Doran, Andrew

    2010-06-09

    Spun-cast films of polystyrene (PS) blended with polylactide (PLA) were visualized and characterized using atomic force microscopy (AFM) and synchrotron-based X-ray photoemission electron microscopy (X-PEEM). The composition of the two polymers in these systems was determined by quantitative chemical analysis of near-edge X-ray absorption signals recorded with X-PEEM. The surface morphology depends on the ratio of the two components, the total polymer concentration, and the temperature of vacuum annealing. For most of the blends examined, PS is the continuous phase with PLA existing in discrete domains or segregated to the air?polymer interface. Phase segregation was improved with further annealing. A phase inversion occurred when films of a 40:60 PS:PLA blend (0.7 wt percent loading) were annealed above the glass transition temperature (Tg) of PLA.

  16. The orphan nuclear receptor NR4A1 (Nur77) regulates oxidative and endoplasmic reticulum stress in pancreatic cancer cells.

    Science.gov (United States)

    Lee, Syng-Ook; Jin, Un-Ho; Kang, Jeong Han; Kim, Sang Bae; Guthrie, Aaron S; Sreevalsan, Sandeep; Lee, Ju-Seog; Safe, Stephen

    2014-04-01

    NR4A1 (Nur77, TR3) is an orphan nuclear receptor that is overexpressed in pancreatic cancer and exhibits pro-oncogenic activity. RNA interference of NR4A1 expression in Panc-1 cells induced apoptosis and subsequent proteomic analysis revealed the induction of several markers of endoplasmic reticulum stress, including glucose-related protein 78 (GRP78), CCAAT/enhancer-binding protein-homologous protein (CHOP), and activating transcription factor-4 (ATF-4). Treatment of pancreatic cancer cells with the NR4A1 antagonist 1,1-bis(3'-indolyl)-1-(p-hydroxyphenyl)methane (DIM-C-pPhOH) gave similar results. Moreover, both NR4A1 knockdown and DIM-C-pPhOH induced reactive oxygen species (ROS), and induction of ROS and endoplasmic reticulum stress by these agents was attenuated after cotreatment with antioxidants. Manipulation of NR4A1 expression coupled with gene expression profiling identified a number of ROS metabolism transcripts regulated by NR4A1. Knockdown of one of these transcripts, thioredoxin domain containing 5 (TXNDC5), recapitulated the elevated ROS and endoplasmic reticulum stress; thus, demonstrating that NR4A1 regulates levels of endoplasmic reticulum stress and ROS in pancreatic cancer cells to facilitate cell proliferation and survival. Finally, inactivation of NR4A1 by knockdown or DIM-C-pPhOH decreased TXNDC5, resulting in activation of the ROS/endoplasmic reticulum stress and proapoptotic pathways. The NR4A1 receptor is pro-oncogenic, regulates the ROS/endoplasmic reticulum stress pathways, and inactivation of the receptor represents a novel pathway for inducing cell death in pancreatic cancer. Mol Cancer Res; 12(4); 527-38. ©2014 AACR.

  17. Si segregation at Fe grain boundaries analyzed by ab initio local energy and local stress

    International Nuclear Information System (INIS)

    Bhattacharya, Somesh Kr; Kohyama, Masanori; Tanaka, Shingo; Shiihara, Yoshinori

    2014-01-01

    Using density-functional theory calculations combined with recent local-energy and local-stress schemes, we studied the effects of Si segregation on the structural, mechanical and magnetic properties of the Σ3(1 1 1) and Σ11(3 3 2) Fe GBs formed by rotation around the [1 1 0] axis. The segregation mechanism was analyzed by the local-energy decomposition of the segregation energy, where the segregation energy is expressed as a sum of the following four terms: the local-energy change of Si atoms from the isolated state in bulk Fe to the GB segregated state, the stabilization of replaced Fe atoms from the GB to the bulk, the local-energy change of neighboring Fe atoms from the pure GB to the segregated GB and the local-energy change of neighboring Fe atoms from the system of an isolated Si atom in the bulk Fe to the pure bulk Fe. The segregation energy and value of each term greatly depends on the segregation site and Si concentration. The segregation at interface Fe sites with higher local energies in the original GB configurations naturally leads to higher segregation-energy gains, while interface sites with lower local energies can lead to larger energy gains if stronger Si–Fe interactions occur locally in the final segregated configurations. The high Si concentration reduces the segregation-energy gain per Si atom due to the local-energy increases of Si atoms neighboring to each other or through the reduction in the number of stabilized Fe atoms per Si atom as observed in a Si dimer in bulk Fe. In the Si-segregated GBs, Si–Fe bonds enhance local Young’s moduli and tend to suppress the interface weakening, while the GB adhesion is slightly reduced. And Fe atoms contacting Si atoms have reduced magnetic moments, due to Si–Fe sp-d hybridization interactions. (paper)

  18. A parametric study of axial segregation in a rotating cylinder.

    Energy Technology Data Exchange (ETDEWEB)

    Bielenberg, J. R. (James R.); Gladysz, G. M. (Gary M.); Graham, Alan L.

    2004-01-01

    When a cylindrical container, partially filled with a binary granular mixture of particles that differ in size or density, is rotated around its axis, a spontaneous segregation of the two granular components may occur. In order to better understand this phenomena, we have carried out an experimental study probing the effect of average particle size and relative size difference between particles on the onset of segregation. The experimental study is followed by a novel scaling analysis that relates the deterministic, convective driving force for particle segregation to the randomizing diffusional driving force present in these systems through the definition of an axial granular Peclet number. This Peclet number based approach will forgo some of the difficulties inherent in full-scale dynamic simulations, but will still allow us to determine the effects of system parameters on the final steady-state that is achieved. Values of this granular Peclet number are shown to successfully correlate with segregation behavior in the present experiment results, as well as in comparable results present in the literature.

  19. 49 CFR 176.83 - Segregation.

    Science.gov (United States)

    2010-10-01

    ... presence of one or more steel bulkheads or decks between them or a combination thereof. Intervening spaces... substance but vary only in their water content (for example, sodium sulfide in Division 4.2 or Class 8) or... applied. (11) Certain exceptions from segregation for waste cyanides or waste cyanide mixtures or...

  20. Protective role of antioxidant vitamin E and catechin on idarubicin-induced cardiotoxicity in rats

    Directory of Open Access Journals (Sweden)

    Kalender S.

    2002-01-01

    Full Text Available Idarubicin is an anthracycline antibiotic extensively used in acute leukemia. In the present study we investigated whether vitamin E and catechin can reduce the toxic effects of idarubicin. Vitamin E (200 IU kg-1 week-1, catechin (200 mg kg-1 week-1, idarubicin (5 mg kg-1 week-1, idarubicin + vitamin E (200 IU kg-1 week-1, and idarubicin + catechin (200 mg kg-1 week-1 combinations were given to male Sprague-Dawley rats weighing 210 to 230 g (N = 6/group. Idarubicin-treated animals exhibited a decrease in body and heart weight, a decrease in myocardial contractility, and changes in ECG parameters (P<0.01. Catechin + idarubicin- and vitamin E + idarubicin-treated groups exhibited similar alterations, but changes were attenuated in comparison to those in cardiac muscle of idarubicin-treated rats (P<0.05. Superoxide dismutase and catalase activity was reduced in the idarubicin-treated group (P<0.05. Glutathione peroxidase levels were decreased in the idarubicin-treated group (P<0.05 and reached maximum concentrations in the catechin- and catechin + idarubicin-treated groups compared to control (P<0.01. Malondialdehyde activity was decreased in the catechin + idarubicin-treated groups compared to control and increased in the other groups, reaching maximum concentrations in the vitamin E-treated group (P<0.01. In electron microscopy studies, swelling of the mitochondria and dilatation of the sarcoplasmic reticulum of myocytes were observed in the idarubicin-treated groups. In groups that were given idarubicin + vitamin E and idarubicin + catechin, the only morphological change was a weak dilatation of the sarcoplasmic reticulum. We conclude that catechin and vitamin E significantly reduce idarubicin-induced cardiotoxicity in rats.

  1. Detection of Sequence-Specific Tyrosine Nitration of Manganese SOD and SERCA in Cardiovascular Disease and Aging

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Shanqin; Ying, Jia; Jiang, Bingbing; Guo, Wei; Adachi, Takeshi; Sharov, Victor; Lazar, Harold; Menzoian, James; Knyushko, Tanya V.; Bigelow, Diana J.; Schoneich, Christian; Cohen, Richard

    2006-06-01

    Nitration of protein tyrosine residues (nY) is a marker of oxidative stress and may alter the biological activity of the modified proteins. The aim of this study was to develop antibodies towards site-specific nY-modified proteins and to use histochemical and immunoblotting to demonstrate protein nitration in tissues. Affinity-purified polyclonal antibodies towards peptides with known nY sites in MnSOD nY-34 and of two adjacent nY in the sarcoplasmic endoplasmic reticulum calcium ATPase (SERCA2 di-nY-294,295) were developed. Kidneys from rats infused with angiotensin II with known MnSOD nY and aorta from atherosclerotic rabbits and aging rat skeletal and cardiac sarcoplasmic reticulum with known SERCA di-nY were used for positive controls. Staining for MnSOD nY-34 was most intense in distal renal tubules and collecting ducts. Staining of atherosclerotic aorta for SERCA2 di-nY was most intense in atherosclerotic plaques. Aging rat skeletal muscle and atherosclerotic aorta and cardiac atrium from human diabetic patients also stained positively. Staining was decreased by sodium dithionite that chemically reduces nitrotyrosine to aminotyrosine, and the antigenic nY-peptide blocked staining for each respective nY site, but not for the other. As previously demonstrated, immunoblotting failed to detect these modified proteins in whole tissue lysates, but did when the proteins were concentrated. Immunohistochemical staining for specific nY-modified tyrosine residues offers the ability to assess the effects of oxidant stress associated with pathological conditions on individual proteins whose function may be affected in specific tissue sites.

  2. Active inhibitor-1 maintains protein hyper-phosphorylation in aging hearts and halts remodeling in failing hearts.

    Science.gov (United States)

    Pritchard, Tracy J; Kawase, Yoshiaki; Haghighi, Kobra; Anjak, Ahmad; Cai, Wenfeng; Jiang, Min; Nicolaou, Persoulla; Pylar, George; Karakikes, Ioannis; Rapti, Kleopatra; Rubinstein, Jack; Hajjar, Roger J; Kranias, Evangelia G

    2013-01-01

    Impaired sarcoplasmic reticulum calcium cycling and depressed contractility are key characteristics in heart failure. Defects in sarcoplasmic reticulum function are characterized by decreased SERCA2a Ca-transport that is partially attributable to dephosphorylation of its regulator phospholamban by increased protein phosphatase 1 activity. Inhibition of protein phosphatase 1 through activation of its endogenous inhibitor-1 has been shown to enhance cardiac Ca-handling and contractility as well as protect from pathological stress remodeling in young mice. In this study, we assessed the long-term effects of inducible expression of constitutively active inhibitor-1 in the adult heart and followed function and remodeling through the aging process, up to 20 months. Mice with inhibitor-1 had normal survival and similar function to WTs. There was no overt remodeling as evidenced by measures of left ventricular end-systolic and diastolic diameters and posterior wall dimensions, heart weight to tibia length ratio, and histology. Higher phosphorylation of phospholamban at both Ser16 and Thr17 was maintained in aged hearts with active inhibitor-1, potentially offsetting the effects of elevated Ser2815-phosphorylation in ryanodine receptor, as there were no increases in arrhythmias under stress conditions in 20-month old mice. Furthermore, long-term expression of active inhibitor-1 via recombinant adeno-associated virus type 9 gene transfer in rats with pressure-overload induced heart failure improved function and prevented remodeling, associated with increased phosphorylation of phospholamban at Ser16 and Thr17. Thus, chronic inhibition of protein phosphatase 1, through increases in active inhibitor-1, does not accelerate age-related cardiomyopathy and gene transfer of this molecule in vivo improves function and halts remodeling in the long term.

  3. FGF-23 dysregulates calcium homeostasis and electrophysiological properties in HL-1 atrial cells.

    Science.gov (United States)

    Kao, Yu-Hsun; Chen, Yao-Chang; Lin, Yung-Kuo; Shiu, Rong-Jie; Chao, Tze-Fan; Chen, Shih-Ann; Chen, Yi-Jen

    2014-08-01

    Fibroblast growth factor (FGF)-23 is a key regulator of phosphate homeostasis. Higher FGF-23 levels are correlated with poor outcomes in cardiovascular diseases. FGF-23 can produce cardiac hypertrophy and increase intracellular calcium, which can change cardiac electrical activity. However, it is not clear whether FGF-23 possesses arrhythmogenic potential through calcium dysregulation. Therefore, the purposes of this study were to evaluate the electrophysiological effects of FGF-23 and identify the underlying mechanisms. Patch clamp, confocal microscope with Fluo-4 fluorescence, and Western blot analyses were used to evaluate the electrophysiological characteristics, calcium homeostasis and calcium regulatory proteins in HL-1 atrial myocytes with and without FGF-23 (10 and 25 ng/mL) incubation for 24 h. FGF-23 (25 ng/mL) increased L-type calcium currents, calcium transient and sarcoplasmic reticulum Ca(2+) contents in HL-1 cells. FGF-23 (25 ng/mL)-treated cells (n = 14) had greater incidences (57%, 17% and 15%, P calcium/calmodulin-dependent protein kinase IIδ and phospholamban (PLB) at threonine 17 but had similar phosphorylation extents of PLB at serine 16, total PLB and sarcoplasmic reticulum Ca(2+) -ATPase protein. Moreover, the FGF receptor inhibitor (PD173074, 10 nM), calmodulin inhibitor (W7, 5 μM) and phospholipase C inhibitor (U73122, 1 μM) attenuated the effects of FGF-23 on calcium/calmodulin-dependent protein kinase II phosphorylation. FGF-23 increases HL-1 cells arrhythmogenesis with calcium dysregulation through modulating calcium-handling proteins. © 2014 Stichting European Society for Clinical Investigation Journal Foundation.

  4. Regulation of basal and reserve cardiac pacemaker function by interactions of cAMP mediated PKA-dependent Ca2+ cycling with surface membrane channels

    Science.gov (United States)

    Vinogradova, Tatiana M.; Lakatta, Edward G.

    2009-01-01

    Decades of intensive research of primary cardiac pacemaker, the sinoatrial node, have established potential roles of specific membrane channels in the generation of the diastolic depolarization, the major mechanism allowing sinoatrial node cells generate spontaneous beating. During the last three decades, multiple studies made either in the isolated sinoatrial node or sinoatrial node cells have demonstrated a pivotal role of Ca2+ and, specifically Ca2+-release from sarcoplasmic reticulum, for spontaneous beating of cardiac pacemaker. Recently, spontaneous, rhythmic local subsarcolemmal Ca2+ releases from ryanodine receptors during late half of the diastolic depolarization have been implicated as a vital factor in the generation of sinoatrial node cells spontaneous firing. Local Ca2+ releases are driven by a unique combination of high basal cAMP production by adenylyl cyclases, high basal cAMP degradation by phosphodiesterases and a high level of cAMP-mediated PKA-dependent phosphorylation. These local Ca2+ releases activate an inward Na+-Ca2+ exchange current which accelerates the terminal diastolic depolarization rate and, thus, controls the spontaneous pacemaker firing. Both the basal primary pacemaker beating rate and its modulation via β-adrenergic receptor stimulation appear to be critically dependent upon intact RyR function and local subsarcolemmal sarcoplasmic reticulum generated Ca2+ releases. This review aspires to integrate the traditional viewpoint that has emphasized the supremacy of the ensemble of surface membrane ion channels in spontaneous firing of the primary cardiac pacemaker, and these novel perspectives of cAMP-mediated PKA-dependent Ca2+ cycling in regulation of the heart pacemaker clock, both in the basal state and during β-adrenergic receptor stimulation. PMID:19573534

  5. Structure-function relation of phospholamban: modulation of channel activity as a potential regulator of SERCA activity.

    Directory of Open Access Journals (Sweden)

    Serena Smeazzetto

    Full Text Available Phospholamban (PLN is a small integral membrane protein, which binds and inhibits in a yet unknown fashion the Ca(2+-ATPase (SERCA in the sarcoplasmic reticulum. When reconstituted in planar lipid bilayers PLN exhibits ion channel activity with a low unitary conductance. From the effect of non-electrolyte polymers on this unitary conductance we estimate a narrow pore with a diameter of ca. 2.2 Å for this channel. This value is similar to that reported for the central pore in the structure of the PLN pentamer. Hence the PLN pentamer, which is in equilibrium with the monomer, is the most likely channel forming structure. Reconstituted PLN mutants, which either stabilize (K27A and R9C or destabilize (I47A the PLN pentamer and also phosphorylated PLN still generate the same unitary conductance of the wt/non-phosphorylated PLN. However the open probability of the phosphorylated PLN and of the R9C mutant is significantly lower than that of the respective wt/non-phosphorylated control. In the context of data on PLN/SERCA interaction and on Ca(2+ accumulation in the sarcoplasmic reticulum the present results are consistent with the view that PLN channel activity could participate in the balancing of charge during Ca(2+ uptake. A reduced total conductance of the K(+ transporting PLN by phosphorylation or by the R9C mutation may stimulate Ca(2+ uptake in the same way as an inhibition of K(+ channels in the SR membrane. The R9C-PLN mutation, a putative cause of dilated cardiomyopathy, might hence affect SERCA activity also via its inherent low open probability.

  6. Molecular Mobility in Phase Segregated Bottlebrush Block Copolymer Melts

    Science.gov (United States)

    Yavitt, Benjamin; Gai, Yue; Song, Dongpo; Winter, H. Henning; Watkins, James

    We investigate the linear viscoelastic behavior of poly(styrene)-block-poly(ethylene oxide) (PS-b-PEO) brush block copolymer (BBCP) materials over a range of vol. fractions and with side chain lengths below the entanglement molecular weights. The high chain mobility of the brush architecture results in rapid micro-phase segregation of the brush copolymer segments, which occurs during thermal annealing at mild temperatures. Master curves of the dynamic moduli were obtained by time-temperature superposition. The reduced degree of chain entanglements leads to a unique liquid-like rheology similar to that of bottlebrush homopolymers, even in the phase segregated state. We also explore the alignment of phase segregated domains at exceptionally low strain amplitudes (γ = 0.01) and mild processing temperatures using small angle X-ray scattering (SAXS). Domain orientation occurred readily at strains within the linear viscoelastic regime without noticeable effect on the moduli. This interplay of high molecular mobility and rapid phase segregation that are exhibited simultaneously in BBCPs is in contrast to the behavior of conventional linear block copolymer (LBCP) analogs and opens up new possibilities for processing BBCP materials for a wide range of nanotechnology applications. NSF Center for Hierarchical Manufacturing at the University of Massachusetts, Amherst (CMMI-1025020).

  7. Radiation-induced grain boundary segregation in austenitic stainless steels

    International Nuclear Information System (INIS)

    Bruemmer, S.M.; Charlot, L.A.; Vetrano, J.S.; Simonen, E.P.

    1994-11-01

    Radiation-induced segregation (RIS) to grain boundaries in Fe-Ni-Cr-Si stainless alloys has been measured as a function of irradiation temperature and dose. Heavy-ion irradiation was used to produce damage levels from 1 to 20 displacements per atom (dpa) at temperatures from 175 to 550 degrees C. Measured Fe, Ni, and Cr segregation increased sharply with irradiation dose (from G to 5 dpa) and temperature (from 175 to about 350 degrees C). However, grain boundary concentrations did not change significantly as dose or temperatures were further increased. Although interfacial compositions were similar, the width of radiation-induced enrichment or depletion profiles increased consistently with increasing dose or temperature. Impurity segregation (Si and P) was also measured, but only Si enrichment appeared to be radiation-induced. Grain boundary Si peaked at levels approaching 10 at% after irradiation doses to 10 dpa at an intermediate temperature of 325 degrees C. No evidence of grain boundary silicide precipitation was detected after irradiation at any temperature. Equilibrium segregation of P was measured in the high-P alloys, but interfacial concentration did not increase with irradiation exposure. Comparisons to reported RIS in neutron-irradiated stainless steels revealed similar grain boundary compositional changes for both major alloying and impurity elements

  8. Evolutionary dynamics of adult stem cells: Comparison of random and immortal strand segregation mechanisms

    OpenAIRE

    Tannenbaum, Emmanuel; Sherley, James L.; Shakhnovich, Eugene I.

    2004-01-01

    This paper develops a point-mutation model describing the evolutionary dynamics of a population of adult stem cells. Such a model may prove useful for quantitative studies of tissue aging and the emergence of cancer. We consider two modes of chromosome segregation: (1) Random segregation, where the daughter chromosomes of a given parent chromosome segregate randomly into the stem cell and its differentiating sister cell. (2) ``Immortal DNA strand'' co-segregation, for which the stem cell reta...

  9. Sexual segregation in marine fish, reptiles, birds and mammals behaviour patterns, mechanisms and conservation implications.

    Science.gov (United States)

    Wearmouth, Victoria J; Sims, David W

    2008-01-01

    Sexual segregation occurs when members of a species separate such that the sexes live apart, either singly or in single-sex groups. It can be broadly categorised into two types: habitat segregation and social segregation. Sexual segregation is a behavioural phenomenon that is widespread in the animal kingdom yet the underlying causes remain poorly understood. Sexual segregation has been widely studied among terrestrial mammals such as ungulates, but it has been less well documented in the marine environment. This chapter clarifies terms and concepts which have emerged from the investigation of sexual segregation in terrestrial ecology and examines how a similar methodological approach may be complicated by differences of marine species. Here we discuss the behavioural patterns of sexual segregation among marine fish, reptile, bird and mammal species. Five hypotheses have been forwarded to account for sexual segregation, largely emerging from investigation of sexual segregation in terrestrial ungulates: the predation risk, forage selection, activity budget, thermal niche-fecundity and social factors hypotheses. These mechanisms are reviewed following careful assessment of their applicability to marine vertebrate species and case studies of marine vertebrates which support each mechanism recounted. Rigorous testing of all hypotheses is lacking from both the terrestrial and marine vertebrate literature and those analyses which have been attempted are often confounded by factors such as sexual body-size dimorphism. In this context, we indicate the value of studying model species which are monomorphic with respect to body size and discuss possible underlying causes for sexual segregation in this species. We also discuss why it is important to understand sexual segregation, for example, by illustrating how differential exploitation of the sexes by humans can lead to population decline.

  10. Residential segregation and birth weight among racial and ethnic minorities in the United States.

    Science.gov (United States)

    Walton, Emily

    2009-12-01

    Racial and ethnic minorities are often residentially segregated from whites in urban settings, a fact which has important health consequences. Research on the relationship between residential segregation and health outcomes lacks national-level investigation of racial and ethnic minority groups other than African Americans. I use multilevel analyses to examine the associations of residential isolation and clustering with birth weight among Asian, black, and Latino Americans using data from the National Center for Health Statistics' Natality Files and the U.S. Census. Findings indicate that segregation has a negative effect on the likelihood of having a low birth weight baby among Asian Americans, suggesting a possible concentration of social and structural resources in highly-segregated communities. On the contrary, segregation marginally increases the odds of low birth weight among African Americans, but only in the presence of higher poverty rates. Segregation does not affect birth weight among Latino Americans.

  11. HMGB1 induces an inflammatory response in endothelial cells via the RAGE-dependent endoplasmic reticulum stress pathway

    International Nuclear Information System (INIS)

    Luo, Ying; Li, Shu-Jun; Yang, Jian; Qiu, Yuan-Zhen; Chen, Fang-Ping

    2013-01-01

    Highlights: •Mechanisms of inflammatory response induced by HMGB1 are incompletely understood. •We found that endoplasmic reticulum stress mediate the inflammatory response induced by HMGB1. •RAGE-mediated ERS pathways are involved in those processes. •We reported a new mechanism for HMGB1 induced inflammatory response. -- Abstract: The high mobility group 1B protein (HMGB1) mediates chronic inflammatory responses in endothelial cells, which play a critical role in atherosclerosis. However, the underlying mechanism is unknown. The goal of our study was to identify the effects of HMGB1 on the RAGE-induced inflammatory response in endothelial cells and test the possible involvement of the endoplasmic reticulum stress pathway. Our results showed that incubation of endothelial cells with HMGB1 (0.01–1 μg/ml) for 24 h induced a dose-dependent activation of endoplasmic reticulum stress transducers, as assessed by PERK and IRE1 protein expression. Moreover, HMGB1 also promoted nuclear translocation of ATF6. HMGB1-mediated ICAM-1 and P-selectin production was dramatically suppressed by PERK siRNA or IRE1 siRNA. However, non-targeting siRNA had no such effects. HMGB1-induced increases in ICAM-1 and P-selectin expression were also inhibited by a specific eIF2α inhibitor (salubrinal) and a specific JNK inhibitor (SP600125). Importantly, a blocking antibody specifically targeted against RAGE (anti-RAGE antibody) decreased ICAM-1, P-selectin and endoplasmic reticulum stress molecule (PERK, eIF2α, IRE1 and JNK) protein expression levels. Collectively, these novel findings suggest that HMGB1 promotes an inflammatory response by inducing the expression of ICAM-1 and P-selectin via RAGE-mediated stimulation of the endoplasmic reticulum stress pathway

  12. Maternal mRNAs of PEM and macho 1, the ascidian muscle determinant, associate and move with a rough endoplasmic reticulum network in the egg cortex.

    Science.gov (United States)

    Sardet, Christian; Nishida, Hiroki; Prodon, Francois; Sawada, Kaichiro

    2003-12-01

    Localization of maternal mRNAs in the egg cortex is an essential feature of polarity in embryos of Drosophila, Xenopus and ascidians. In ascidians, maternal mRNAs such as macho 1, a determinant of primary muscle-cell fate, belong to a class of postplasmic RNAs that are located along the animal-vegetal gradient in the egg cortex. Between fertilization and cleavage, these postplasmic RNAs relocate in two main phases. They further concentrate and segregate in small posterior blastomeres into a cortical structure, the centrosome-attracting body (CAB), which is responsible for unequal cleavages. By using high-resolution, fluorescent, in situ hybridization in eggs, zygotes and embryos of Halocynthia roretzi, we showed that macho 1 and HrPEM are localized on a reticulated structure situated within 2 mum of the surface of the unfertilized egg, and within 8 mum of the surface the vegetal region and then posterior region of the zygote. By isolating cortices from eggs and zygotes we demonstrated that this reticulated structure is a network of cortical rough endoplasmic reticulum (cER) that is tethered to the plasma membrane. The postplasmic RNAs macho 1 and HrPEM were located on the cER network and could be detached from it. We also show that macho 1 and HrPEM accumulated in the CAB and the cER network. We propose that these postplasmic RNAs relocalized after fertilization by following the microfilament- and microtubule-driven translocations of the cER network to the poles of the zygote. We also suggest that the RNAs segregate and concentrate in posterior blastomeres through compaction of the cER to form the CAB. A multimedia BioClip 'Polarity inside the egg cortex' tells the story and can be downloaded at www.bioclips.com/bioclip.html

  13. Thermodynamic effect of elastic stress on grain boundary segregation of phosphorus in a low alloy steel

    International Nuclear Information System (INIS)

    Zheng, Lei; Lejček, Pavel; Song, Shenhua; Schmitz, Guido; Meng, Ye

    2015-01-01

    Grain boundary (GB) segregation of P in 2.25Cr1Mo steel induced by elastic stress shows that the P equilibrium concentration, after reaching the non-equilibrium concentration maximum at critical time, returns to its initial thermal equilibrium level. This finding confirms the interesting phenomenon that the effect of elastic stress on GB segregation of P is significant in kinetics while slight in thermodynamics. Through extending the “pressure” in classical theory of chemical potential to the “elastic stress”, the thermodynamic effect of elastic stress on GB segregation is studied, and the relationship between elastic stress and segregation Gibbs energy is formulated. The formulas reveal that the difference in the segregation Gibbs energy between the elastically-stressed and non-stressed states depends on the excess molar volume of GB segregation and the magnitude of elastic stress. Model calculations in segregation Gibbs energy confirm that the effect of elastic stress on the thermodynamics of equilibrium GB segregation is slight, and the theoretical analyses considerably agree with the experimental results. The confirmation indicates that the nature of the thermodynamic effect is well captured. - Highlights: • GB segregation of P after stress aging returns to its initial thermal equilibrium level. • Relationship between elastic stress and segregation energy is formulated. • Thermodynamic effect relies on excess molar volume and magnitude of elastic stress. • Effect of elastic stress on Gibbs energy of GB segregation is estimated to be slight. • Complete theory of the effect of elastic stress on grain boundary segregation is setup

  14. Radiation use in measurement and control of cement and fine aggregate segregation in mortar

    International Nuclear Information System (INIS)

    Veado, Maria Adelaide Rabelo Vasconcelos.

    1991-09-01

    Segregation of solid particles in a mortar for structural purposes was measured by a nuclear method in which the grains were marked by neutron activation. The influence of vibration time on segregation was studied, and the method was capable of detecting a segregation trend, that is a higher concentration of cement and finer aggregate particles in the upper longer of the specimens. Results were more significant when the finer grains were marked rather than. The coarser ones, due to statistical constraints imposed by the smaller quantities of the latter. The Segregation increased with increasing vibration times. The validity of the proposed nuclear method for segregation measurements has been confirmed. (author). 15 refs., 5 figs., 19 tabs

  15. Grain boundary phosphorus segregation under thermal aging in low alloy steels

    International Nuclear Information System (INIS)

    Nakata, Hayato; Fujii, Katsuhiko; Fukuya, Koji; Shibata, Masaaki; Kasada, Ryuta; Kimura, Akihiko

    2002-01-01

    Intergranular embrittlement due to grain boundary segregation of phosphorus is recognized as one of the potential degradation factors in irradiated reactor pressure vessel steels at high neutron fluences. In this study, investigations on low alloy steels thermally aged at 400-500degC were conducted to evaluate the correlation between phosphorus segregation and intergranular embrittlement. Phosphorus segregation determined using Auger electron spectroscopy increased after aging above 450degC and was in good agreement with the calculated value based on McLean model. No influence of thermal aging was observed in tensile properties. The ductile brittle transition temperature determined using 1/3 size charpy impact tests increased of 12degC after aging at 450degC for 3000 hours. These results indicated that there is a threshold level of phosphorus segregation for non-hardening embrittlement and that the level is around 0.14 for P/Fe peak ratio. (author)

  16. Grain boundary phosphorus segregation under thermal aging in low alloy steels

    Energy Technology Data Exchange (ETDEWEB)

    Nakata, Hayato; Fujii, Katsuhiko; Fukuya, Koji [Inst. of Nuclear Safety System Inc., Mihama, Fukui (Japan); Shibata, Masaaki; Kasada, Ryuta; Kimura, Akihiko [Kyoto Univ. (Japan)

    2002-09-01

    Intergranular embrittlement due to grain boundary segregation of phosphorus is recognized as one of the potential degradation factors in irradiated reactor pressure vessel steels at high neutron fluences. In this study, investigations on low alloy steels thermally aged at 400-500degC were conducted to evaluate the correlation between phosphorus segregation and intergranular embrittlement. Phosphorus segregation determined using Auger electron spectroscopy increased after aging above 450degC and was in good agreement with the calculated value based on McLean model. No influence of thermal aging was observed in tensile properties. The ductile brittle transition temperature determined using 1/3 size charpy impact tests increased of 12degC after aging at 450degC for 3000 hours. These results indicated that there is a threshold level of phosphorus segregation for non-hardening embrittlement and that the level is around 0.14 for P/Fe peak ratio. (author)

  17. Segregation of a binary granular mixture in a vibrating sawtooth base container.

    Science.gov (United States)

    Mobarakabadi, Shahin; Adrang, Neda; Habibi, Mehdi; Oskoee, Ehsan Nedaaee

    2017-09-01

    A granular mixture of identical particles of different densities can be segregated when the system is shaken. We present an efficient method of continuously segregating a flow of randomly mixed identical spherical particles of different densities by shaking them in a quasi-two-dimensional container with a sawtooth-shaped base. Using numerical simulation we study the effect of direction of shaking (horizontal/vertical), geometry of the sawtooth, and the friction coefficient between the grains and the container walls on the segregation quality. Finally by performing experiments on the same system we compare our simulation results with the experimental results. The good agreement between our simulation and experiment indicates the validity of our simulation approach and will provide a practical way for granular segregation in industrial applications.

  18. Ricin A chain reaches the endoplasmic reticulum after endocytosis

    International Nuclear Information System (INIS)

    Liu Qiong; Zhan Jinbiao; Chen Xinhong; Zheng Shu

    2006-01-01

    Ricin is a potent ribosome inactivating protein and now has been widely used for synthesis of immunotoxins. To target ribosome in the mammalian cytosol, ricin must firstly retrograde transport from the endomembrane system to reach the endoplasmic reticulum (ER) where the ricin A chain (RTA) is recognized by ER components that facilitate its membrane translocation to the cytosol. In the study, the fusion gene of enhanced green fluorescent protein (EGFP)-RTA was expressed with the pET-28a (+) system in Escherichia coli under the control of a T7 promoter. The fusion protein showed a green fluorescence. The recombinant protein can be purified by metal chelated affinity chromatography on a column of NTA. The rabbit anti-GFP antibody can recognize the fusion protein of EGFP-RTA just like the EGFP protein. The cytotoxicity of EGFP-RTA and RTA was evaluated by the MTT assay in HeLa and HEP-G2 cells following fluid-phase endocytosis. The fusion protein had a similar cytotoxicity of RTA. After endocytosis, the subcellular location of the fusion protein can be observed with the laser scanning confocal microscopy and the immuno-gold labeling Electro Microscopy. This study provided important evidence by a visualized way to prove that RTA does reach the endoplasmic reticulum

  19. Catenin-dependent cadherin function drives divisional segregation of spinal motor neurons.

    Science.gov (United States)

    Bello, Sanusi M; Millo, Hadas; Rajebhosale, Manisha; Price, Stephen R

    2012-01-11

    Motor neurons that control limb movements are organized as a neuronal nucleus in the developing ventral horn of the spinal cord called the lateral motor column. Neuronal migration segregates motor neurons into distinct lateral and medial divisions within the lateral motor column that project axons to dorsal or ventral limb targets, respectively. This migratory phase is followed by an aggregation phase whereby motor neurons within a division that project to the same muscle cluster together. These later phases of motor neuron organization depend on limb-regulated differential cadherin expression within motor neurons. Initially, all motor neurons display the same cadherin expression profile, which coincides with the migratory phase of motor neuron segregation. Here, we show that this early, pan-motor neuron cadherin function drives the divisional segregation of spinal motor neurons in the chicken embryo by controlling motor neuron migration. We manipulated pan-motor neuron cadherin function through dissociation of cadherin binding to their intracellular partners. We found that of the major intracellular transducers of cadherin signaling, γ-catenin and α-catenin predominate in the lateral motor column. In vivo manipulations that uncouple cadherin-catenin binding disrupt divisional segregation via deficits in motor neuron migration. Additionally, reduction of the expression of cadherin-7, a cadherin predominantly expressed in motor neurons only during their migration, also perturbs divisional segregation. Our results show that γ-catenin-dependent cadherin function is required for spinal motor neuron migration and divisional segregation and suggest a prolonged role for cadherin expression in all phases of motor neuron organization.

  20. The metabolomic signature of Leber's hereditary optic neuropathy reveals endoplasmic reticulum stress.

    Science.gov (United States)

    Chao de la Barca, Juan Manuel; Simard, Gilles; Amati-Bonneau, Patrizia; Safiedeen, Zainab; Prunier-Mirebeau, Delphine; Chupin, Stéphanie; Gadras, Cédric; Tessier, Lydie; Gueguen, Naïg; Chevrollier, Arnaud; Desquiret-Dumas, Valérie; Ferré, Marc; Bris, Céline; Kouassi Nzoughet, Judith; Bocca, Cinzia; Leruez, Stéphanie; Verny, Christophe; Miléa, Dan; Bonneau, Dominique; Lenaers, Guy; Martinez, M Carmen; Procaccio, Vincent; Reynier, Pascal

    2016-11-01

    Leber's hereditary optic neuropathy (MIM#535000), the commonest mitochondrial DNA-related disease, is caused by mutations affecting mitochondrial complex I. The clinical expression of the disorder, usually occurring in young adults, is typically characterized by subacute, usually sequential, bilateral visual loss, resulting from the degeneration of retinal ganglion cells. As the precise action of mitochondrial DNA mutations on the overall cell metabolism in Leber's hereditary optic neuropathy is unknown, we investigated the metabolomic profile of the disease. High performance liquid chromatography coupled with tandem mass spectrometry was used to quantify 188 metabolites in fibroblasts from 16 patients with Leber's hereditary optic neuropathy and eight healthy control subjects. Latent variable-based statistical methods were used to identify discriminating metabolites. One hundred and twenty-four of the metabolites were considered to be accurately quantified. A supervised orthogonal partial least squares discriminant analysis model separating patients with Leber's hereditary optic neuropathy from control subjects showed good predictive capability (Q 2cumulated = 0.57). Thirty-eight metabolites appeared to be the most significant variables, defining a Leber's hereditary optic neuropathy metabolic signature that revealed decreased concentrations of all proteinogenic amino acids, spermidine, putrescine, isovaleryl-carnitine, propionyl-carnitine and five sphingomyelin species, together with increased concentrations of 10 phosphatidylcholine species. This signature was not reproduced by the inhibition of complex I with rotenone or piericidin A in control fibroblasts. The importance of sphingomyelins and phosphatidylcholines in the Leber's hereditary optic neuropathy signature, together with the decreased amino acid pool, suggested an involvement of the endoplasmic reticulum. This was confirmed by the significantly increased phosphorylation of PERK and eIF2α, as well as

  1. Segregation in welded nickel-base alloys

    International Nuclear Information System (INIS)

    Akhtar, J.I.; Shoaib, K.A.; Ahmad, M.; Shaikh, M.A.

    1990-05-01

    Segregation effects have been investigated in nickel-base alloys monel 400, inconel 625, hastelloy C-276 and incoloy 825, test welded under controlled conditions. Deviations from the normal composition have been observed to varying extents in the welded zone of these alloys. Least effect of this type occurred in Monel 400 where the content of Cu increased in some of the areas. Enhancement of Al and Ti has been found over large areas in the other alloys which has been attributed to the formation of low melting slag. Another common feature is the segregation of Cr, Fe or Ti, most likely in the form of carbides. Enrichment of Al, Ti, Nb, Mb, Mo, etc., to different amounts in some of the areas of these materials is in- terpretted in terms of the formation of gamma prime precipitates or of Laves phases. (author)

  2. Kinetic Monte Carlo simulation of surface segregation in Pd–Cu alloys

    International Nuclear Information System (INIS)

    Cheng, Feng; He, Xiang; Chen, Zhao-Xu; Huang, Yu-Gai

    2015-01-01

    The knowledge of surface composition and atomic arrangement is prerequisite for understanding of catalytic properties of an alloy catalyst. Gaining such knowledge is rather difficult, especially for those possessing surface segregation. Pd–Cu alloy is used in many fields and possesses surface segregation. In this paper kinetic Monte Carlo method is used to explore the surface composition and structure and to examine the effects of bulk composition and temperature on the surface segregation of Pd–Cu alloys. It is shown that the segregation basically completes within 900 s at 500 K. Below 900 K and within 20 min the enriched surface Cu atoms mainly come from the top five layers. For the first time we demonstrate that there exists a “bulk-inside flocking” or clustering phenomenon (the same component element congregates in bulk) in Pd–Cu alloys. Our results indicate that for alloys with higher Cu content there are small Pd ensembles like monomers, dimers and trimers with contiguous subsurface Pd atoms. - Highlights: • Kinetic Monte Carlo was first used to study surface segregation of Pd–Cu alloys. • Bulk-inside flocking (the same component element congregates in bulk) was observed. • Small Pd ensembles with contiguous subsurface Pd exist on surfaces of Cu-rich alloys

  3. Unpackaging residential segregation: the importance of scale and informal market processes

    Directory of Open Access Journals (Sweden)

    Peter M. Ward

    2010-06-01

    Full Text Available This paper addresses two principal issues: a the scale at which one examines urban segregation; and b how informality, specifically accessibility to land markets and the process of land appropriation by low-income groups in Latin American cities, influences segregation patterns. Using Mexico City as a case study for Latin America, it shows that macro residential segregation levels are not becoming more polarized as many believe, due to informality of the market place and the weak state intervention through planning and zoning. However, there is a hardening of boundaries between adjacent neighborhoods as people turn to gated communities, largely for security reasons. Case study material from three Mexican cities are presented to examine how the nature of residential land costs and market segmentation contributes to segregation in Latin American cities. In a second case study, data from peri-urban low-income self-build settlements (colonias in Texas cities demonstrate how existing inequality patterns can be reproduced by differential access to land markets. They further argue a case that such isolated (rural settlements serving nearby urban labor market, should also be included in any analysis of urban segregation patterns, even if they do not form part of the contiguous urban area.

  4. Kinetic Monte Carlo simulation of surface segregation in Pd–Cu alloys

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, Feng [Institute of Theoretical and Computational Chemistry, School of Chemistry and Chemical Engineering, Key Laboratory of Mesoscopic Chemistry of MOE, Nanjing University (China); He, Xiang [Nanjing Institute of Geography and Limnology, Chinese Academy of Sciences, Nanjing 210008 (China); Chen, Zhao-Xu, E-mail: zxchen@nju.edu.cn [Institute of Theoretical and Computational Chemistry, School of Chemistry and Chemical Engineering, Key Laboratory of Mesoscopic Chemistry of MOE, Nanjing University (China); Huang, Yu-Gai [Institute of Theoretical and Computational Chemistry, School of Chemistry and Chemical Engineering, Key Laboratory of Mesoscopic Chemistry of MOE, Nanjing University (China); JiangSu Second Normal University, Nanjing (China)

    2015-11-05

    The knowledge of surface composition and atomic arrangement is prerequisite for understanding of catalytic properties of an alloy catalyst. Gaining such knowledge is rather difficult, especially for those possessing surface segregation. Pd–Cu alloy is used in many fields and possesses surface segregation. In this paper kinetic Monte Carlo method is used to explore the surface composition and structure and to examine the effects of bulk composition and temperature on the surface segregation of Pd–Cu alloys. It is shown that the segregation basically completes within 900 s at 500 K. Below 900 K and within 20 min the enriched surface Cu atoms mainly come from the top five layers. For the first time we demonstrate that there exists a “bulk-inside flocking” or clustering phenomenon (the same component element congregates in bulk) in Pd–Cu alloys. Our results indicate that for alloys with higher Cu content there are small Pd ensembles like monomers, dimers and trimers with contiguous subsurface Pd atoms. - Highlights: • Kinetic Monte Carlo was first used to study surface segregation of Pd–Cu alloys. • Bulk-inside flocking (the same component element congregates in bulk) was observed. • Small Pd ensembles with contiguous subsurface Pd exist on surfaces of Cu-rich alloys.

  5. How Segregation Makes Us Fat: Food Behaviors and Food Environment as Mediators of the Relationship Between Residential Segregation and Individual Body Mass Index

    OpenAIRE

    Melody Goodman; Sarah Lyons; Lorraine T. Dean; Cassandra Arroyo; James Aaron Hipp

    2018-01-01

    ObjectivesRacial residential segregation affects food landscapes that dictate residents’ food environments and is associated with obesity risk factors, including individual dietary patterns and behaviors. We examine if food behaviors and environments mediate the association between segregation and body mass index (BMI).MethodsNon-Hispanic Whites and Blacks living in the St. Louis and Kansas City metro regions from 2012 to 2013 were surveyed on dietary behaviors, food environment, and BMI (n =...

  6. Effects of two medicinal plants Psidium guajava L. (Myrtaceae) and Diospyros mespiliformis L. (Ebenaceae) leaf extracts on rat skeletal muscle cells in primary culture

    Science.gov (United States)

    Belemtougri, R.G.; Constantin, B.; Cognard, C.; Raymond, G.; Sawadogo, L.

    2006-01-01

    Crude decoction, aqueous and ethanolic extracts of two medicinal plants (Psidium guajava and Diospyros mespiliformis), widely used in the central plateau of Burkina Faso to treat many diseases were evaluated for their antagonistic effects on caffeine induced calcium release from sarcoplasmic reticulum of rat skeletal muscle cells. These different extracts showed a decrease of caffeine induced calcium release in a dose dependent manner. Comparison of the results showed that Psidium guajava leaf extracts are more active than extracts of Diospyros mespiliformis and that crude decoctions show better inhibitory activity. The observed results could explaine their use as antihypertensive and antidiarrhoeal agents in traditional medicine, by inhibiting intracellular calcium release. PMID:16365927

  7. Ca2+-clock-dependent pacemaking in the sinus node is impaired in mice with a cardiac specific reduction in SERCA2 abundance

    Directory of Open Access Journals (Sweden)

    Sunil Jit Ramamoorthy Jeewanlal Logantha

    2016-06-01

    Full Text Available Background: The sarcoplasmic reticulum Ca2+-ATPase (SERCA2 pump is an important component of the Ca2+-clock pacemaker mechanism that provides robustness and flexibility to sinus node pacemaking. We have developed transgenic mice with reduced cardiac SERCA2 abundance (Serca2 KO as a model for investigating SERCA2’s role in sinus node pacemaking.Methods and Results: In Serca2 KO mice, ventricular SERCA2a protein content measured by Western blotting was 75% (P70% Serca2 downregulation.Conclusions: Serca2 KO mice show a disrupted Ca2+-clock-dependent pacemaker mechanism contributing to impaired sinus node and atrioventricular node function.

  8. The Ca2+ pump inhibitor, thapsigargin, inhibits root gravitropism in Arabidopsis thaliana

    Directory of Open Access Journals (Sweden)

    DANIELA C URBINA

    2006-01-01

    Full Text Available Thapsigargin, a specific inhibitor of most animal intracellular SERCA-type Ca2+ pumps present in the sarcoplasmic/endoplasmic reticulum, was originally isolated from the roots of the Mediterranean plant Thapsia gargancia L. Here, we demonstrate that this root-derived compound is capable of altering root gravitropism in Arabidopsis thaliana. Thapsigargin concentrations as low as 0.1 µM alter root gravitropism whereas under similar conditions cyclopiazonic acid does not. Furthermore, a fluorescently conjugated thapsigargin (BODIPY FL thapsigargin suggests that target sites for thapsigargin are located in intracellular organelles in the root distal elongation zone and the root cap, regions known to regulate root gravitropism

  9. The road to understanding an ion pump

    Science.gov (United States)

    Toyoshima, Chikashi

    2016-04-01

    In the past 25 years or so I have been working almost exclusively on two proteins: the Ca2+-ATPase of muscle sarcoplasmic reticulum, and the Na+, K+-ATPase expressed in all animal cells, both are membrane ion pumps representing P-type ion translocating ATPases. My ambition as a scientist is to completely understand the meaning of their atomic structures. How I became a scientist is described elsewhere (Nuzzo R 2006 Proc. Natl. Acad. Sci. USA 103 1165-7), and focus here is given to my struggle towards a deep understanding of Ca2+-ATPase. This is a long but very fascinating and rewarding journey.

  10. Organellar Calcium Buffers

    Science.gov (United States)

    Prins, Daniel; Michalak, Marek

    2011-01-01

    Ca2+ is an important intracellular messenger affecting many diverse processes. In eukaryotic cells, Ca2+ storage is achieved within specific intracellular organelles, especially the endoplasmic/sarcoplasmic reticulum, in which Ca2+ is buffered by specific proteins known as Ca2+ buffers. Ca2+ buffers are a diverse group of proteins, varying in their affinities and capacities for Ca2+, but they typically also carry out other functions within the cell. The wide range of organelles containing Ca2+ and the evidence supporting cross-talk between these organelles suggest the existence of a dynamic network of organellar Ca2+ signaling, mediated by a variety of organellar Ca2+ buffers. PMID:21421925

  11. A role for recombination junctions in the segregation of mitochondrial DNA in yeast.

    Science.gov (United States)

    Lockshon, D; Zweifel, S G; Freeman-Cook, L L; Lorimer, H E; Brewer, B J; Fangman, W L

    1995-06-16

    In S. cerevisiae, mitochondrial DNA (mtDNA) molecules, in spite of their high copy number, segregate as if there were a small number of heritable units. The rapid segregation of mitochondrial genomes can be analyzed using mtDNA deletion variants. These small, amplified genomes segregate preferentially from mixed zygotes relative to wild-type mtDNA. This segregation advantage is abolished by mutations in a gene, MGT1, that encodes a recombination junction-resolving enzyme. We show here that resolvase deficiency causes a larger proportion of molecules to be linked together by recombination junctions, resulting in the aggregation of mtDNA into a small number of cytological structures. This change in mtDNA structure can account for the increased mitotic loss of mtDNA and the altered pattern of mtDNA segregation from zygotes. We propose that the level of unresolved recombination junctions influences the number of heritable units of mtDNA.

  12. Segregation and the gender wage gaps in the private and the public sector

    DEFF Research Database (Denmark)

    Albæk, Karsten; Larsen, Mona; Stage Thomsen, Lars

    2016-01-01

    This paper examines the relation between segregation and the gender wage gap in the public and the private sectors in Denmark from 2002 to 2012. The analysis shows that male–female differences in the share of females in occupations, industries,establishments and job cells (occupations within...... establishments) constitute 46% of the raw gender wage gap in the private sector, while segregation in t he public sector accounts for as much as 63 %. Segregation thus plays a substantially more important role in accounting for the gender wage gap in the public sector than in the private sector. While...... the importance of segregation for wage formation decreased substantially in the public sector over time, it only decreased slightly in the private sector. Although the remaining gender wage gap, after controlling for segregation, is close to zero in the public sector, a substantial within-job cell differential...

  13. Combined equilibrium and non-equilibrium phosphorus segregation to grain boundaries in a 2.25Cr1Mo steel

    International Nuclear Information System (INIS)

    Song, S.-H.; Shen, D.-D.; Yuan, Z.-X.; Liu, J.; Xu, T.-D.; Weng, L.-Q.

    2003-01-01

    Grain boundary segregation of phosphorus in a P-doped 2.25Cr1Mo steel during ageing at 540 deg. C after quenching from 980 deg. C is examined by Auger electron spectroscopy. The segregation is a combined effect of equilibrium segregation and non-equilibrium segregation. The effect of phosphorus non-equilibrium segregation is to enhance the kinetics of its equilibrium segregation

  14. Dislocation and void segregation in copper during neutron irradiation

    DEFF Research Database (Denmark)

    Singh, Bachu Narain; Leffers, Torben; Horsewell, Andy

    1986-01-01

    ); the irradiation experiments were carried out at 250 degree C. The irradiated specimens were examined by transmission electron microscopy. At both doses, the irradiation-induced structure was found to be highly segregated; the dislocation loops and segments were present in the form of irregular walls and the voids...... density, the void swelling rate was very high (approximately 2. 5% per dpa). The implications of the segregated distribution of sinks for void formation and growth are briefly discussed....

  15. Plasmid and chromosome segregation in prokaryotes

    DEFF Research Database (Denmark)

    Møller-Jensen, Jakob; Bugge Jensen, Rasmus; Gerdes, Kenn

    2000-01-01

    Recent major advances in the understanding of prokaryotic DNA segregation have been achieved by using fluorescence microscopy to visualize the localization of cellular components. Plasmids and bacterial chromosomes are partitioned in a highly dynamic fashion, suggesting the presence of a mitotic...

  16. Positive segregation as a function of buoyancy force during steel ingot solidification

    International Nuclear Information System (INIS)

    Radovic, Zarko; Jaukovic, Nada; Lalovic, Milisav; Tadic, Nebojsa

    2008-01-01

    We analyze theoretically and experimentally solute redistribution in the dendritic solidification process and positive segregation during solidification of steel ingots. Positive segregation is mainly caused by liquid flow in the mushy zone. Changes in the liquid steel velocity are caused by the temperature gradient and by the increase in the solid fraction during solidification. The effects of buoyancy and of the change in the solid fraction on segregation intensity are analyzed. The relationships between the density change, liquid fraction and the steel composition are considered. Such elements as W, Ni, Mo and Cr decrease the effect of the density variations, i.e. they show smaller tendency to segregate. Based on the modeling and experimental results, coefficients are provided controlling the effects of chemical composition, secondary dendrite arm spacing and the solid fraction.

  17. Segregation in Religion Networks

    OpenAIRE

    Hu, Jiantao; Zhang, Qian-Ming; Zhou, Tao

    2018-01-01

    Religious beliefs could facilitate human cooperation [1-6], promote civic engagement [7-10], improve life satisfaction [11-13] and even boom economic development [14-16]. On the other side, some aspects of religion may lead to regional violence, intergroup conflict and moral prejudice against atheists [17-23]. Analogous to the separation of races [24], the religious segregation is a major ingredient resulting in increasing alienation, misunderstanding, cultural conflict and even violence amon...

  18. Segregation of acetylcholine and GABA in the rat superior cervical ganglia: functional correlation.

    Directory of Open Access Journals (Sweden)

    Diana eElinos

    2016-04-01

    Full Text Available Sympathetic neurons have the capability to segregate their neurotransmitters (NTs and co-transmitters to separate varicosities of single axons; furthermore, in culture, these neurons can even segregate classical transmitters. In vivo sympathetic neurons employ acetylcholine (ACh and other classical NTs such as gamma aminobutyric acid (GABA. Herein, we explore whether these neurons in vivo segregate these classical NTs in the superior cervical ganglia of the rat. We determined the topographical distribution of GABAergic varicosities, somatic GABAA receptor, as well as the regional distribution of the segregation of ACh and GABA. We evaluated possible regional differences in efficacy of ganglionic synaptic transmission, in the sensitivity of GABAA receptor to GABA and to the competitive antagonist picrotoxin (PTX. We found that sympathetic preganglionic neurons in vivo do segregate ACh and GABA. GABAergic varicosities and GABAA receptor expression showed a rostro-caudal gradient along ganglia; in contrast, segregation exhibited a caudo-rostral gradient. These uneven regional distributions in expression of GABA, GABAA receptors, and level segregation correlate with stronger synaptic transmission found in the caudal region. Accordingly, GABAA receptors of rostral region show larger sensitivity to GABA and PTX. These results suggest the presence of different types of GABAA receptors in each region that result in a different regional levels of endogenous GABA inhibition. Finally, we discuss a possible correlation of these different levels of GABA modulation and the function of the target organs innervated by rostral and caudal ganglionic neurons.

  19. Ceramide transport from endoplasmic reticulum to Golgi apparatus is not vesicle-mediated

    NARCIS (Netherlands)

    Kok, JW; Babia, T; Klappe, K; Egea, G; Hoekstra, D

    1998-01-01

    Ceramide (Cer) transfer from the endoplasmic reticulum (ER) to the Golgi apparatus was measured under conditions that block vesicle-mediated protein transfer. This was done either in intact cells by reducing the incubation temperature to 15 degrees C, or in streptolysin O-permeabilized cells by

  20. Weak-beam electron microscopy of radiation-induced segregation

    International Nuclear Information System (INIS)

    Saka, H.

    1983-01-01

    The segregation of solute atoms to dislocations during irradiation by 1 MeV electrons in a HVEM was studied by measuring the dissociation width of extended dislocations in Cu-5.1 at.%Si, Cu-5.3 at.%Ge, Ag-9.4 at.% In and Ag-9.6 at.%Al alloys. 'Weak-beam' electron microscopy was used. In Cu-Si (oversized solute), Cu-Ge (oversize) and Ag-Al (undersize), solute enrichment was observed near dislocations, while in Ag-In (oversize) solute depletion was observed. The results are discussed in terms of current mechanisms for radiation-induced segregation. (author)

  1. Marketization, occupational segregation, and gender earnings inequality in urban China.

    Science.gov (United States)

    He, Guangye; Wu, Xiaogang

    2017-07-01

    This article analyzes a large sample of the 2005 population mini-census data and prefecture-level statistics of China to investigate gender earnings inequality in the context of economic marketization, paying special attention to the changing role of occupational segregation in the process. We approximate marketization by employment sectors and also construct an index of marketization at the prefecture level. Results show that, despite the tremendous economic growth, marketization has exacerbated gender earnings inequality in urban China's labor markets. Gender earnings inequality is the smallest in government/public institutions, followed by public enterprises, and then private enterprises. The gender inequality also increases with the prefecture's level of marketization. Multilevel analyses show that occupational segregation plays an important role in affecting gender earnings inequality: the greater the occupational segregation, the more disadvantaged women are relative to men in earnings in a prefecture's labor market. Moreover, the impact of occupational segregation on gender earnings inequality increases with the prefectural level of marketization. These findings contribute to understanding the dynamics of gender earnings inequality and have important implications for policy to promote gender equality in urban China. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Brain bases for auditory stimulus-driven figure-ground segregation.

    Science.gov (United States)

    Teki, Sundeep; Chait, Maria; Kumar, Sukhbinder; von Kriegstein, Katharina; Griffiths, Timothy D

    2011-01-05

    Auditory figure-ground segregation, listeners' ability to selectively hear out a sound of interest from a background of competing sounds, is a fundamental aspect of scene analysis. In contrast to the disordered acoustic environment we experience during everyday listening, most studies of auditory segregation have used relatively simple, temporally regular signals. We developed a new figure-ground stimulus that incorporates stochastic variation of the figure and background that captures the rich spectrotemporal complexity of natural acoustic scenes. Figure and background signals overlap in spectrotemporal space, but vary in the statistics of fluctuation, such that the only way to extract the figure is by integrating the patterns over time and frequency. Our behavioral results demonstrate that human listeners are remarkably sensitive to the appearance of such figures. In a functional magnetic resonance imaging experiment, aimed at investigating preattentive, stimulus-driven, auditory segregation mechanisms, naive subjects listened to these stimuli while performing an irrelevant task. Results demonstrate significant activations in the intraparietal sulcus (IPS) and the superior temporal sulcus related to bottom-up, stimulus-driven figure-ground decomposition. We did not observe any significant activation in the primary auditory cortex. Our results support a role for automatic, bottom-up mechanisms in the IPS in mediating stimulus-driven, auditory figure-ground segregation, which is consistent with accumulating evidence implicating the IPS in structuring sensory input and perceptual organization.

  3. Sex segregation and equality in a multicultural society: inferiority as a standard for legal acceptability

    Directory of Open Access Journals (Sweden)

    Marjolein van den Brink

    2010-06-01

    Full Text Available This contribution explores the legal acceptability of old and new forms of sex segregation, using a multilayered ‘inferiority test’ that can be regarded as a specification of (international equality and non-discrimination standards. The test is applied to a number of topical cases of sex segregation: 1 A traditional case of rather uncontested sex segregation in sports, specifically in amateur football; 2 A more controversial case that seems to be on the rise once again: sex-segregated education; 3 The highly controversial case of sex-segregated integration courses in the Netherlands. The outcome shows that each sex-segregated practice is problematic in the light of one or more criteria of this inferiority test, but not necessarily the same criteria. Specific attention is paid to the merits of the test in a multicultural context. The inferiority test is a useful tool in dealing with multicultural complexity, although not in every respect. It allows the impact of sex segregation on minority women to be taken into account, as well as cultural and religious reasons which women may have in demanding sex-segregation facilities, unless this will result in perpetuating their or other women’s subordination. Our findings suggest that the inferiority test is quite useful as an analytical tool to assess contested practices of sex segregation. However, the multilayered character of the test needs some fine-tuning when the various elements of the test lead to different conclusions.

  4. Hating the Neighbors: The Role of Hate Crime in the Perpetuation of Black Residential Segregation

    Directory of Open Access Journals (Sweden)

    Ami M. Lynch

    2008-06-01

    Full Text Available Grounded in group conflict theory and the defended neighborhoods thesis, this nationwide empirical study of cities and their residential segregation levels examines the occurrence of hate crime using data for all U.S. cities with populations over 95,000 and Uniform Crime Reporting data for hate crime, in conjunction with 2000 census data. Hate crime is any illegal act motivated by pre-formed bias against, in this case, a person’s real or perceived race. This research asks: Do hate crime levels predict white/black segregation levels? How does hate crime predict different measures of white/black segregation? I use the dissimilarity index measure of segregation operationalized as a continuous, binary, and ordinal variable, to explore whether hate crime predicts segrega- tion of blacks from whites. In cities with higher rates of hate crime there was higher dissimilarity between whites and blacks, controlling for other factors. The segregation level was more likely to be “high” in a city where hate crime occurred. Blacks are continually multiply disadvantaged and distinctly affected by hate crime and residential segregation. Prior studies of residential segregation have focused almost exclusively on individual choice, residents’ lack of finances, or discriminatory actions that prevent racial minorities from moving, to explore the correlates of segregation. Notably absent from these studies are measures reflecting the level of hate crime occurring in cities. This study demonstrates the importance of considering hate crime and neighborhood conflict when contemplating the causes of residential segregation.

  5. Segregation of solute elements at grain boundaries in an ultrafine grained Al-Zn-Mg-Cu alloy

    International Nuclear Information System (INIS)

    Sha, Gang; Yao, Lan; Liao, Xiaozhou; Ringer, Simon P.; Chao Duan, Zhi; Langdon, Terence G.

    2011-01-01

    The solute segregation at grain boundaries (GBs) of an ultrafine grained (UFG) Al-Zn-Mg-Cu alloy processed by equal-channel angular pressing (ECAP) at 200 o C was characterised using three-dimensional atom probe. Mg and Cu segregate strongly to the grain boundaries. In contrast, Zn does not always show clear segregation and may even show depletion near the grain boundaries. Trace element Si selectively segregates at some GBs. An increase in the number of ECAP passes leads to a decrease in the grain size but an increase in solute segregation at the boundaries. The significant segregation of alloying elements at the boundaries of ultrafine-grained alloys implies that less solutes will be available in the matrix for precipitation with a decrease in the average grain size. -- Research Highlights: → Atom probe tomography has been employed successfully to reveal unique segregation of solutes at ultrafine grained material. → Mg and Cu elements segregated strongly at the grain boundary of an ultrafine grained Al-Zn-Mg-Cu alloy processed by 4-pass and 8-pass ECAP at 200 o C. Zn frequently depleted at GBs with a Zn depletion region of 7-15 nm in width on one or both sides of the GBs. Only a small fraction (3/13) of GBs were observed with a low level of Zn segregation where the combined Mg and Cu excess is over 3.1 atom/nm 2 . Si appeared selectively segregated at some of the GBs. → The increase in number of ECAP passes from 4 to 8 correlated with the increase in mean level segregation of Mg and Cu for both solute excess and peak concentration. → The change of plane normal of a grain boundary within 30 o only leads to a slight change in the solute segregation level.

  6. Gender Segregation: Separate but Effective?

    Science.gov (United States)

    Holthouse, David

    2010-01-01

    In 2002, only 11 public schools in the United States had gender-segregated classrooms. As of December 2009, there were more than 550. The movement is based on the hypothesis that hard-wired differences in the ways that male and female brains develop and function in childhood through adolescence require classrooms in which boys and girls are not…

  7. The time course of perceptual grouping: the role of segregation and shape formation.

    Science.gov (United States)

    Razpurker-Apfeld, Irene; Kimchi, Ruth

    2007-07-01

    The time course of perceptual grouping was examined in two experiments, using a primed matching task. In different conditions, elements were grouped into columns/rows by common lightness, into a shape (triangle/ arrow or square/cross) by common lightness, and into a shape without segregation of elements. The results showed an early and rapid grouping into columns/rows by common lightness and into a shape when no segregation from other elements was involved. Goodness of shape (i.e., triangle/arrow vs. square/cross) had no influence on how early grouping was evident, but the relatively poorer shapes appeared to consolidate with time. In contrast, grouping into a shape that involved segregation and required resolving figure-ground relations between segregated units, as grouping into a shape by common lightness, consumed time, regardless of shape goodness. These results suggest that the time course of grouping varies as a function of the processes involved in it (e.g., segregation and shape formation) and the conditions prevailing for each process.

  8. The involvement of SMILE/TMTC3 in endoplasmic reticulum stress response.

    Directory of Open Access Journals (Sweden)

    Maud Racapé

    Full Text Available The state of operational tolerance has been detected sporadically in some renal transplanted patients that stopped immunosuppressive drugs, demonstrating that allograft tolerance might exist in humans. Several years ago, a study by Brouard et al. identified a molecular signature of several genes that were significantly differentially expressed in the blood of such patients compared with patients with other clinical situations. The aim of the present study is to analyze the role of one of these molecules over-expressed in the blood of operationally tolerant patients, SMILE or TMTC3, a protein whose function is still unknown.We first confirmed that SMILE mRNA is differentially expressed in the blood of operationally tolerant patients with drug-free long term graft function compared to stable and rejecting patients. Using a yeast two-hybrid approach and a colocalization study by confocal microscopy we furthermore report an interaction of SMILE with PDIA3, a molecule resident in the endoplasmic reticulum (ER. In accordance with this observation, SMILE silencing in HeLa cells correlated with the modulation of several transcripts involved in proteolysis and a decrease in proteasome activity. Finally, SMILE silencing increased HeLa cell sensitivity to the proteasome inhibitor Bortezomib, a drug that induces ER stress via protein overload, and increased transcript expression of a stress response protein, XBP-1, in HeLa cells and keratinocytes.In this study we showed that SMILE is involved in the endoplasmic reticulum stress response, by modulating proteasome activity and XBP-1 transcript expression. This function of SMILE may influence immune cell behavior in the context of transplantation, and the analysis of endoplasmic reticulum stress in transplantation may reveal new pathways of regulation in long-term graft acceptance thereby increasing our understanding of tolerance.

  9. Temporal resolution of orientation-defined texture segregation: a VEP study.

    Science.gov (United States)

    Lachapelle, Julie; McKerral, Michelle; Jauffret, Colin; Bach, Michael

    2008-09-01

    Orientation is one of the visual dimensions that subserve figure-ground discrimination. A spatial gradient in orientation leads to "texture segregation", which is thought to be concurrent parallel processing across the visual field, without scanning. In the visual-evoked potential (VEP) a component can be isolated which is related to texture segregation ("tsVEP"). Our objective was to evaluate the temporal frequency dependence of the tsVEP to compare processing speed of low-level features (e.g., orientation, using the VEP, here denoted llVEP) with texture segregation because of a recent literature controversy in that regard. Visual-evoked potentials (VEPs) were recorded in seven normal adults. Oriented line segments of 0.1 degrees x 0.8 degrees at 100% contrast were presented in four different arrangements: either oriented in parallel for two homogeneous stimuli (from which were obtained the low-level VEP (llVEP)) or with a 90 degrees orientation gradient for two textured ones (from which were obtained the texture VEP). The orientation texture condition was presented at eight different temporal frequencies ranging from 7.5 to 45 Hz. Fourier analysis was used to isolate low-level components at the pattern-change frequency and texture-segregation components at half that frequency. For all subjects, there was lower high-cutoff frequency for tsVEP than for llVEPs, on average 12 Hz vs. 17 Hz (P = 0.017). The results suggest that the processing of feature gradients to extract texture segregation requires additional processing time, resulting in a lower fusion frequency.

  10. Growth mechanism of graphene on platinum: Surface catalysis and carbon segregation

    International Nuclear Information System (INIS)

    Sun, Jie; Lindvall, Niclas; Yurgens, August; Nam, Youngwoo; Cole, Matthew T.; Teo, Kenneth B. K.; Woo Park, Yung

    2014-01-01

    A model of the graphene growth mechanism of chemical vapor deposition on platinum is proposed and verified by experiments. Surface catalysis and carbon segregation occur, respectively, at high and low temperatures in the process, representing the so-called balance and segregation regimes. Catalysis leads to self-limiting formation of large area monolayer graphene, whereas segregation results in multilayers, which evidently “grow from below.” By controlling kinetic factors, dominantly monolayer graphene whose high quality has been confirmed by quantum Hall measurement can be deposited on platinum with hydrogen-rich environment, quench cooling, tiny but continuous methane flow and about 1000 °C growth temperature

  11. A method for the study of surface segregation in multicomponent alloys

    International Nuclear Information System (INIS)

    Gargano, Pablo; Mosca, Hugo; Bozzolo, Guillermo

    2009-01-01

    A simple algorithm for the determination of segregation profiles in multicomponent systems based on a mean field formalism and a quantum approximate method for the energetics is introduced. The method is described and applied to two ternary systems, concentrating on the changes in segregation patterns relative to the corresponding binary cases.

  12. Sources of Segregation in Social Networks : A Novel Approach Using Facebook

    NARCIS (Netherlands)

    Hofstra, B.; Corten, R.; van Tubergen, F.A.; Ellison, Nicole

    2017-01-01

    Most research on segregation in social networks considers small circles of strong ties, and little is known about segregation among the much larger number of weaker ties. This article proposes a novel approach to the study of these more extended networks, through the use of data on personal ties in

  13. Solute grain boundary segregation during high temperature plastic deformation in a Cr-Mo low alloy steel

    International Nuclear Information System (INIS)

    Chen, X.-M.; Song, S.-H.; Weng, L.-Q.; Liu, S.-J.

    2011-01-01

    Highlights: → The segregation of P and Mo is evidently enhanced by plastic deformation. → The boundary concentrations of P and Mo increase with increasing strain. → A model with consideration of site competition in grain boundary segregation in a ternary system is developed. → Model predictions show a reasonable agreement with the observations. - Abstract: Grain boundary segregation of Cr, Mo and P to austenite grain boundaries in a P-doped 1Cr0.5Mo steel is examined using field emission gun scanning transmission electron microscopy for the specimens undeformed and deformed by 10% with a strain rate of 2 x 10 -3 s -1 at 900 deg. C, and subsequently water quenched to room temperature. Before deformation, there is some segregation for Mo and P, but the segregation is considerably increased after deformation. The segregation of Cr is very small and there is no apparent difference between the undeformed and deformed specimens. Since the thermal equilibrium segregation has been attained prior to deformation, the segregation produced during deformation has a non-equilibrium characteristic. A theoretical model with consideration of site competition in grain boundary segregation between two solutes in a ternary alloy is developed to explain the experimental results. Model predictions are made, which show a reasonable agreement with the observations.

  14. State-related functional integration and functional segregation brain networks in schizophrenia.

    Science.gov (United States)

    Yu, Qingbao; Sui, Jing; Kiehl, Kent A; Pearlson, Godfrey; Calhoun, Vince D

    2013-11-01

    Altered topological properties of brain connectivity networks have emerged as important features of schizophrenia. The aim of this study was to investigate how the state-related modulations to graph measures of functional integration and functional segregation brain networks are disrupted in schizophrenia. Firstly, resting state and auditory oddball discrimination (AOD) fMRI data of healthy controls (HCs) and schizophrenia patients (SZs) were decomposed into spatially independent components (ICs) by group independent component analysis (ICA). Then, weighted positive and negative functional integration (inter-component networks) and functional segregation (intra-component networks) brain networks were built in each subject. Subsequently, connectivity strength, clustering coefficient, and global efficiency of all brain networks were statistically compared between groups (HCs and SZs) in each state and between states (rest and AOD) within group. We found that graph measures of negative functional integration brain network and several positive functional segregation brain networks were altered in schizophrenia during AOD task. The metrics of positive functional integration brain network and one positive functional segregation brain network were higher during the resting state than during the AOD task only in HCs. These findings imply that state-related characteristics of both functional integration and functional segregation brain networks are impaired in schizophrenia which provides new insight into the altered brain performance in this brain disorder. © 2013.

  15. Dipeptidyl peptidase-4 inhibitor, vildagliptin, inhibits pancreatic beta cell apoptosis in association with its effects suppressing endoplasmic reticulum stress in db/db mice.

    Science.gov (United States)

    Wu, Yan-ju; Guo, Xin; Li, Chun-jun; Li, Dai-qing; Zhang, Jie; Yang, Yiping; Kong, Yan; Guo, Hang; Liu, De-min; Chen, Li-ming

    2015-02-01

    Vildagliptin promotes beta cell survival by inhibiting cell apoptosis. It has been suggested that chronic ER (endoplasmic reticulum) stress triggers beta cell apoptosis. The objective of the study is to explore whether the pro-survival effect of vildagliptin is associated with attenuation of endoplasmic reticulum stress in islets of db/db mice. Vildagliptin was orally administered to db/db mice for 6 weeks, followed by evaluation of beta cell apoptosis by caspase3 activity and TUNEL staining method. Endoplasmic reticulum stress markers were determined with quantitative RT-PCR, immunohistochemistry and immunoblot analysis. After 6 weeks of treatment, vildagliptin treatment increased plasma active GLP-1 levels (22.63±1.19 vs. 11.69±0.44, Pvildagliptin treatment down-regulated several genes related to endoplasmic reticulum stress including TRIB3 (tribbles homolog 3) (15.9±0.4 vs. 33.3±1.7, ×10⁻³, PVildagliptin promoted beta cell survival in db/db mice in association with down-regulating markers of endoplasmic reticulum stress including TRIB3, ATF-4 as well as CHOP. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  16. Segregation of solid waste from a fish-processing industry: a sustainable action

    Directory of Open Access Journals (Sweden)

    Yeda dos Santos Silva

    2018-05-01

    Full Text Available Segregation techniques represent a sustainable alternative to minimize wastes of raw material in processing industries. This study considered the premise; its purpose was to use segregation techniques to determine the theoretical removal rate of solid compounds present in processing effluents, in order to support the sustainable development of the fish industry. The removal rates obtained for different treatments were evaluated for the parameters: total solids, organic matter and oils and greases, and the efficiency of the segregation of the effluent streams in the different stages of fish processing was evaluated through descriptive statistical analysis. The segregation recovered from 31% to 70% of total solids; from 15% to 97.50% of organic matter, and from 10% to 63% of oils and greases. These results indicates that the raw material can be used in new products, leading to reduced final-effluent concentration.

  17. Diffusion and segregation of substrate copper in electrodeposited Ni-Fe thin films

    International Nuclear Information System (INIS)

    Ahadian, M.M.; Iraji zad, A.; Nouri, E.; Ranjbar, M.; Dolati, A.

    2007-01-01

    The Cu surface segregation is investigated in the electrodeposited Ni-Fe layers using X-ray photoelectron spectroscopy (XPS), Auger electron spectroscopy (AES), secondary ion mass spectroscopy (SIMS) and atomic force microscopy (AFM). The results indicate that Cu segregation and accumulation take place in areated and deareated baths and the amount of segregated copper increases after air exposure. This phenomenon is explained by lower interfacial tension of the Cu in comparison with Ni and Fe. Our results reveal more surface segregation in the electrodeposit than vacuum reported results. This should be due to interface charging and higher surface diffusion in applied potential. The effect of interface charging on the interfacial tension is discussed based on Lippmann equation. Increasing of the Cu accumulation after air exposure is related to selective oxidation in alloys and higher tendency of Cu to surface oxidation

  18. Implementing spatial segregation measures in R.

    Directory of Open Access Journals (Sweden)

    Seong-Yun Hong

    Full Text Available Reliable and accurate estimation of residential segregation between population groups is important for understanding the extent of social cohesion and integration in our society. Although there have been considerable methodological advances in the measurement of segregation over the last several decades, the recently developed measures have not been widely used in the literature, in part due to their complex calculation. To address this problem, we have implemented several newly proposed segregation indices in R, an open source software environment for statistical computing and graphics, as a package called seg. Although there are already a few standalone applications and add-on packages that provide access to similar methods, our implementation has a number of advantages over the existing tools. First, our implementation is flexible in the sense that it provides detailed control over the calculation process with a wide range of input parameters. Most of the parameters have carefully chosen defaults, which perform acceptably in many situations, so less experienced users can also use the implemented functions without too much difficulty. Second, there is no need to export results to other software programs for further analysis. We provide coercion methods that enable the transformation of our output classes into general R classes, so the user can use thousands of standard and modern statistical techniques, which are already available in R, for the post-processing of the results. Third, our implementation does not require commercial software to operate, so it is accessible to a wider group of people.

  19. Grain boundary diffusion and segregation of Ni in Cu

    International Nuclear Information System (INIS)

    Divinski, Sergiy; Ribbe, Jens; Schmitz, Guido; Herzig, Christian

    2007-01-01

    Grain boundary (GB) diffusion of 63 Ni in polycrystalline Cu was investigated by the radiotracer technique in an extended temperature interval from 476 to 1156K. The independent measurements in Harrison's C and B kinetic regimes resulted in direct data of the GB diffusivity D gb and of the so-called triple product P=s.δ.D gb (s and δ are the segregation factor and the diffusional GB width, respectively). Arrhenius-type temperature dependencies for both the D gb and P values were measured, resulting in the pre-exponential factors D gb 0 =6.93x10 -7 m 2 s -1 and P 0 =1.89x10 -16 m 3 s -1 and the activation enthalpies of 90.4 and 73.8kJmol -1 , respectively. Although Ni is completely soluble in Cu, it reveals a distinct but still moderate ability to segregate copper GBs with a segregation enthalpy of about -17kJmol -1

  20. Sphingosine inhibits the sarco(endo)plasmic reticulum Ca{sup 2+}-ATPase (SERCA) activity

    Energy Technology Data Exchange (ETDEWEB)

    Benaim, Gustavo, E-mail: gbenaim@idea.gob.ve [Instituto de Estudios Avanzados (IDEA), Caracas (Venezuela, Bolivarian Republic of); Instituto de Biología Experimental, Facultad de Ciencias, Universidad Central de Venezuela (UCV), Caracas (Venezuela, Bolivarian Republic of); Pimentel, Adriana A., E-mail: adriana.pimentel@ucv.ve [Facultad de Farmacia, Universidad Central de Venezuela (UCV), Caracas (Venezuela, Bolivarian Republic of); Felibertt, Pimali [Facultad de Ciencias, Universidad de Carabobo, Valencia (Venezuela, Bolivarian Republic of); Mayora, Adriana [Instituto de Biología Experimental, Facultad de Ciencias, Universidad Central de Venezuela (UCV), Caracas (Venezuela, Bolivarian Republic of); Colman, Laura [Instituto Pasteur de Montevideo, Montevideo (Uruguay); Sojo, Felipe [Instituto de Biología Experimental, Facultad de Ciencias, Universidad Central de Venezuela (UCV), Caracas (Venezuela, Bolivarian Republic of); Rojas, Héctor [Instituto de Inmunología, Universidad Central de Venezuela (UCV), Caracas (Venezuela, Bolivarian Republic of); Centro de Biofísica y Bioquímica, Instituto Venezolano de Investigaciones Científicas (IVIC), Caracas (Venezuela, Bolivarian Republic of); De Sanctis, Juan B. [Instituto de Inmunología, Universidad Central de Venezuela (UCV), Caracas (Venezuela, Bolivarian Republic of)

    2016-04-29

    The increase in the intracellular Ca{sup 2+} concentration ([Ca{sup 2+}]{sub i}) is the key variable for many different processes, ranging from regulation of cell proliferation to apoptosis. In this work we demonstrated that the sphingolipid sphingosine (Sph) increases the [Ca{sup 2+}]{sub i} by inhibiting the sarco(endo)plasmic reticulum Ca{sup 2+}-ATPase (SERCA), in a similar manner to thapsigargin (Tg), a specific inhibitor of this Ca{sup 2+} pump. The results showed that addition of sphingosine produced a release of Ca{sup 2+} from the endoplasmic reticulum followed by a Ca{sup 2+} entrance from the outside mileu. The results presented in this work support that this sphingolipid could control the activity of the SERCA, and hence sphingosine may participate in the regulation of [Ca{sup 2+}]{sub I} in mammalian cells.

  1. Segregation, Choice Based Letting and Social Housing : How Housing Policy Can Affect the Segregation Process (discussion paper)

    NARCIS (Netherlands)

    Van Ham, M.; Manley, D.J.

    2012-01-01

    In this chapter we investigate the process of ethnic minority segregation in English social housing. Successive governments have expressed a commitment to the contradictory aims of providing greater choice – through the introduction of choice based letting – for households accessing an increasingly

  2. 14 CFR 1206.202 - Deletion of segregable portions of a record.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Deletion of segregable portions of a record... AVAILABILITY OF AGENCY RECORDS TO MEMBERS OF THE PUBLIC Records Available § 1206.202 Deletion of segregable... that indication would harm an interest protected by the exemption in Subpart 3 under which the deletion...

  3. 76 FR 22414 - Amended Proposed Withdrawal, Notice of Public Meetings, Partial Termination of Segregative Effect...

    Science.gov (United States)

    2011-04-21

    ... Withdrawal, Notice of Public Meetings, Partial Termination of Segregative Effect; Arizona, California... the proposed SEZs to include some additional lands. It also terminates the segregative effect as to... proposal is cancelled and the segregative effect established by the June 30, 2009, Notice of Proposed...

  4. Ring-like size segregation in vibrated cylinder with a bottleneck

    International Nuclear Information System (INIS)

    Kong Xiangzhao; Hu Maobin; Wu Qingsong; Wu Yonghong

    2005-01-01

    In this Letter, a ring-like segregation pattern of bi-dispersed granular material in a vibrated bottleneck-cylinder is presented. The driving frequency can greatly affect the strength and structure of the convection roll and segregation pattern. The position and height of the ring (cluster of big beads) can be adjusted by altering the vibration frequency. And a heuristic theory is developed to interpret the ring's position dependence on driving frequency

  5. Auditory stream segregation using bandpass noises: evidence from event-related potentials

    Directory of Open Access Journals (Sweden)

    Yingjiu eNie

    2014-09-01

    Full Text Available The current study measured neural responses to investigate auditory stream segregation of noise stimuli with or without clear spectral contrast. Sequences of alternating A and B noise bursts were presented to elicit stream segregation in normal-hearing listeners. The successive B bursts in each sequence maintained an equal amount of temporal separation with manipulations introduced on the last stimulus. The last B burst was either delayed for 50% of the sequences or not delayed for the other 50%. The A bursts were jittered in between every two adjacent B bursts. To study the effects of spectral separation on streaming, the A and B bursts were further manipulated by using either bandpass-filtered noises widely spaced in center frequency or broadband noises. Event-related potentials (ERPs to the last B bursts were analyzed to compare the neural responses to the delay vs. no-delay trials in both passive and attentive listening conditions. In the passive listening condition, a trend for a possible late mismatch negativity (MMN or late discriminative negativity (LDN response was observed only when the A and B bursts were spectrally separate, suggesting that spectral separation in the A and B burst sequences could be conducive to stream segregation at the pre-attentive level. In the attentive condition, a P300 response was consistently elicited regardless of whether there was spectral separation between the A and B bursts, indicating the facilitative role of voluntary attention in stream segregation. The results suggest that reliable ERP measures can be used as indirect indicators for auditory stream segregation in conditions of weak spectral contrast. These findings have important implications for cochlear implant (CI studies – as spectral information available through a CI device or simulation is substantially degraded, it may require more attention to achieve stream segregation.

  6. Grain boundary phosphorus segregation under thermal aging in low alloy steels

    International Nuclear Information System (INIS)

    Nakata, Hayato; Fujii, Katsuhiko; Fukuya, Koji; Kasada, Ryuta; Kimura, Akihiko

    2007-01-01

    Intergranular embrittlement due to grain boundary segregation of phosphorus is recognized as one of the potential degradation factors in irradiated reactor low alloy steels at high neutron fluence. In this study, low alloy steels thermally aged at 400-500degC were investigated to evaluate the correlation between phosphorus segregation and intergranular embrittlement. Phosphorus segregation determined using Auger electron spectroscopy increased after thermal aging above 450degC and was in good agreement with the calculated value based on McLean's model. No influence of thermal aging on tensile properties or hardness was observed. The ductile brittle transition temperature determined using a one-third size Charpy impact test increased at a P/Fe peak ratio of 0.14. These results indicated that there is a threshold level of phosphorus segregation for non-hardening embrittlement. DBTT increased with the proportion of intergranular fracture, so this result shows that there is a relationship between DBTT and the properties of intergranular fracture. The fracture stress decreases due to non-hardening embrittlement on the thermally aged material with high proportion of intergranular fracture. (author)

  7. The luminosity of galactic components and morphological segregation

    International Nuclear Information System (INIS)

    Solanes, J. M.; Salvador-Sole, E.; Sanroma, M.

    1989-01-01

    The luminosities of the bulge and disk components of disk galaxies are analyzed, and the possible correlation of these luminosities with morphological type and local density is explored. Galaxies of different types are found to be located in distinct bands in the bulge-to-disk luminosity ratio vs total luminosity diagram, allowing the determination of the typical bulge luminosity function of disk galaxies of different types from their respective total luminosity functions, along with a better characterization of morphological segregation among disk galaxies. No evidence for any bulge luminosity segregation is found, and disks appear to be less luminous with increasing local density. 33 refs

  8. Segregation of a binary granular mixture in a vibrating sawtooth base container

    NARCIS (Netherlands)

    Mobarakabadi, Shahin; Adrang, Neda; Habibi, Mehdi; Oskoee, Ehsan Nedaaee

    2017-01-01

    Abstract.: A granular mixture of identical particles of different densities can be segregated when the system is shaken. We present an efficient method of continuously segregating a flow of randomly mixed identical spherical particles of different densities by shaking them in a

  9. CENP-A regulates chromosome segregation during the first meiosis of mouse oocytes.

    Science.gov (United States)

    Li, Li; Qi, Shu-Tao; Sun, Qing-Yuan; Chen, Shi-Ling

    2017-06-01

    Proper chromosome separation in both mitosis and meiosis depends on the correct connection between kinetochores of chromosomes and spindle microtubules. Kinetochore dysfunction can lead to unequal distribution of chromosomes during cell division and result in aneuploidy, thus kinetochores are critical for faithful segregation of chromosomes. Centromere protein A (CENP-A) is an important component of the inner kinetochore plate. Multiple studies in mitosis have found that deficiencies in CENP-A could result in structural and functional changes of kinetochores, leading to abnormal chromosome segregation, aneuploidy and apoptosis in cells. Here we report the expression and function of CENP-A during mouse oocyte meiosis. Our study found that microinjection of CENP-A blocking antibody resulted in errors of homologous chromosome segregation and caused aneuploidy in eggs. Thus, our findings provide evidence that CENP-A is critical for the faithful chromosome segregation during mammalian oocyte meiosis.

  10. Sister chromatid segregation in meiosis II

    Science.gov (United States)

    Wassmann, Katja

    2013-01-01

    Meiotic divisions (meiosis I and II) are specialized cell divisions to generate haploid gametes. The first meiotic division with the separation of chromosomes is named reductional division. The second division, which takes place immediately after meiosis I without intervening S-phase, is equational, with the separation of sister chromatids, similar to mitosis. This meiotic segregation pattern requires the two-step removal of the cohesin complex holding sister chromatids together: cohesin is removed from chromosome arms that have been subjected to homologous recombination in meiosis I and from the centromere region in meiosis II. Cohesin in the centromere region is protected from removal in meiosis I, but this protection has to be removed—deprotected”—for sister chromatid segregation in meiosis II. Whereas the mechanisms of cohesin protection are quite well understood, the mechanisms of deprotection have been largely unknown until recently. In this review I summarize our current knowledge on cohesin deprotection. PMID:23574717

  11. New atom probe approaches to studying segregation in nanocrystalline materials

    International Nuclear Information System (INIS)

    Samudrala, S.K.; Felfer, P.J.; Araullo-Peters, V.J.; Cao, Y.; Liao, X.Z.; Cairney, J.M.

    2013-01-01

    Atom probe is a technique that is highly suited to the study of nanocrystalline materials. It can provide accurate atomic-scale information about the composition of grain boundaries in three dimensions. In this paper we have analysed the microstructure of a nanocrystalline super-duplex stainless steel prepared by high pressure torsion (HPT). Not all of the grain boundaries in this alloy display obvious segregation, making visualisation of the microstructure challenging. In addition, the grain boundaries present in the atom probe data acquired from this alloy have complex shapes that are curved at the scale of the dataset and the interfacial excess varies considerably over the boundaries, making the accurate characterisation of the distribution of solute challenging using existing analysis techniques. In this paper we present two new data treatment methods that allow the visualisation of boundaries with little or no segregation, the delineation of boundaries for further analysis and the quantitative analysis of Gibbsian interfacial excess at boundaries, including the capability of excess mapping. - Highlights: ► New data treatment methods allow delineation of grain boundaries, even without segregation. ► Proxigrams calculated from the surfaces accurately show the extent of segregation. ► Tessellation of the data volume can be used to map the Gibbsian interfacial excess

  12. New atom probe approaches to studying segregation in nanocrystalline materials

    Energy Technology Data Exchange (ETDEWEB)

    Samudrala, S.K.; Felfer, P.J.; Araullo-Peters, V.J. [School of Aerospace, Mechanical and Mechatronic Engineering, University of Sydney, NSW 2006 (Australia); The Australian Centre for Microscopy and Microanalysis, The University of Sydney, NSW 2006 (Australia); Cao, Y.; Liao, X.Z. [School of Aerospace, Mechanical and Mechatronic Engineering, University of Sydney, NSW 2006 (Australia); Cairney, J.M., E-mail: julie.cairney@sydney.edu.au [School of Aerospace, Mechanical and Mechatronic Engineering, University of Sydney, NSW 2006 (Australia); The Australian Centre for Microscopy and Microanalysis, The University of Sydney, NSW 2006 (Australia)

    2013-09-15

    Atom probe is a technique that is highly suited to the study of nanocrystalline materials. It can provide accurate atomic-scale information about the composition of grain boundaries in three dimensions. In this paper we have analysed the microstructure of a nanocrystalline super-duplex stainless steel prepared by high pressure torsion (HPT). Not all of the grain boundaries in this alloy display obvious segregation, making visualisation of the microstructure challenging. In addition, the grain boundaries present in the atom probe data acquired from this alloy have complex shapes that are curved at the scale of the dataset and the interfacial excess varies considerably over the boundaries, making the accurate characterisation of the distribution of solute challenging using existing analysis techniques. In this paper we present two new data treatment methods that allow the visualisation of boundaries with little or no segregation, the delineation of boundaries for further analysis and the quantitative analysis of Gibbsian interfacial excess at boundaries, including the capability of excess mapping. - Highlights: ► New data treatment methods allow delineation of grain boundaries, even without segregation. ► Proxigrams calculated from the surfaces accurately show the extent of segregation. ► Tessellation of the data volume can be used to map the Gibbsian interfacial excess.

  13. Controlling mixing and segregation in time periodic granular flows

    Science.gov (United States)

    Bhattacharya, Tathagata

    Segregation is a major problem for many solids processing industries. Differences in particle size or density can lead to flow-induced segregation. In the present work, we employ the discrete element method (DEM)---one type of particle dynamics (PD) technique---to investigate the mixing and segregation of granular material in some prototypical solid handling devices, such as a rotating drum and chute. In DEM, one calculates the trajectories of individual particles based on Newton's laws of motion by employing suitable contact force models and a collision detection algorithm. Recently, it has been suggested that segregation in particle mixers can be thwarted if the particle flow is inverted at a rate above a critical forcing frequency. Further, it has been hypothesized that, for a rotating drum, the effectiveness of this technique can be linked to the probability distribution of the number of times a particle passes through the flowing layer per rotation of the drum. In the first portion of this work, various configurations of solid mixers are numerically and experimentally studied to investigate the conditions for improved mixing in light of these hypotheses. Besides rotating drums, many studies of granular flow have focused on gravity driven chute flows owing to its practical importance in granular transportation and to the fact that the relative simplicity of this type of flow allows for development and testing of new theories. In this part of the work, we observe the deposition behavior of both mono-sized and polydisperse dry granular materials in an inclined chute flow. The effects of different parameters such as chute angle, particle size, falling height and charge amount on the mass fraction distribution of granular materials after deposition are investigated. The simulation results obtained using DEM are compared with the experimental findings and a high degree of agreement is observed. Tuning of the underlying contact force parameters allows the achievement

  14. The quality control of glycoprotein folding in the endoplasmic reticulum, a trip from trypanosomes to mammals

    Directory of Open Access Journals (Sweden)

    A.J. Parodi

    1998-05-01

    Full Text Available The present review deals with the stages of synthesis and processing of asparagine-linked oligosaccharides occurring in the lumen of the endoplasmic reticulum and their relationship to the acquisition by glycoproteins of their proper tertiary structures. Special emphasis is placed on reactions taking place in trypanosomatid protozoa since their study has allowed the detection of the transient glucosylation of glycoproteins catalyzed by UDP-Glc:glycoprotein glucosyltransferase and glucosidase II. The former enzyme has the unique property of covalently tagging improperly folded conformations by catalyzing the formation of protein-linked Glc1Man7GlcNAc2, Glc1Man8GlcNac2 and Glc1Man9GlcNAc2 from the unglucosylated proteins. Glucosyltransferase is a soluble protein of the endoplasmic reticulum that recognizes protein domains exposed in denatured but not in native conformations (probably hydrophobic amino acids and the innermost N-acetylglucosamine unit that is hidden from macromolecular probes in most native glycoproteins. In vivo, the glucose units are removed by glucosidase II. The influence of oligosaccharides in glycoprotein folding is reviewed as well as the participation of endoplasmic reticulum chaperones (calnexin and calreticulin that recognize monoglucosylated species in the same process. A model for the quality control of glycoprotein folding in the endoplasmic reticulum, i.e., the mechanism by which cells recognize the tertiary structure of glycoproteins and only allow transit to the Golgi apparatus of properly folded species, is discussed. The main elements of this control are calnexin and calreticulin as retaining components, the UDP-Glc:glycoprotein glucosyltransferase as a sensor of tertiary structures and glucosidase II as the releasing agent.

  15. Segregation of a copper-nickel alloy after electron irradiation

    International Nuclear Information System (INIS)

    Wagner, W.

    1979-09-01

    In the present work measurement of diffuse neutron scattering are used to determine short range segregation effects of the alloy Cu 0 sub(.) 414 Ni 0 sub(.) 586 after thermal annealing and 3 MeV electron irradiation in the temperature range between 370 K and 600 K. In addition neutron small angle scattering measurement are performed after irradiation to study possible long range segregation effects. Residual resistivity measurements are performed in parallel in order tp orientate the relatively expensive neutron scattering measurements with respect to the residual changes (orig./KBI) [de

  16. The intergranular segregation of boron in substoichiometric Ni/sub 3/Al

    Energy Technology Data Exchange (ETDEWEB)

    Choudhury, A.

    1987-12-01

    The intermetallic compound Ni/sub 3/Al offers promise as a material for high temperature applications. In addition to its unusual property of increasing strength with temperature (until approx.700/sup 0/C), it has excellent corrosion and oxidation resistance. Microalloying the alloy with boron has been shown to be dramatically effective in improving its inherent intergranular brittleness. This improvement results from the strong tendency of boron to segregate to the grain boundaries of Ni/sub 3/Al. This research deals with the study of the segregation behavior of boron. Auger electron spectroscopy was chosen as the technique adopted to study this segregation. The strong effect of segregant level on the grain boundary strength level can be controlled by thermal history variations and by variations in the level of solute in the bulk. Cathodic hydrogen charging was shown to be a potent tool in opening up other wise cohesive boundaries for analysis. The effective binding energy of boron at the grain boundaries of Ni/sub 3/Al was calculated from experimental data; it was found to vary between 0.2 and 0.45 eV. Kinetics of segregation have been investigated; the present set of kinetic studies were shown to be inadequate to find a diffusion coefficient and that temperatures lower than those studied here need to be used. As an associated investigation, a set of elemental standards were developed for the particular scanning Auger microprobe used in this study. 141 refs., 94 figs., 26 tabs.

  17. Socioeconomic Segregation in Large Cities in France and the United States.

    Science.gov (United States)

    Quillian, Lincoln; Lagrange, Hugues

    2016-08-01

    Past cross-national comparisons of socioeconomic segregation have been undercut by lack of comparability in measures, data, and concepts. Using IRIS data from the French Census of 2008 and the French Ministry of Finance as well as tract data from the American Community Survey (2006-2010) and the U.S. Department of Housing and Urban Development Picture of Subsidized Households, and constructing measures to be as similar as possible, we compare socioeconomic segregation in metropolitan areas with a population of more than 1 million in France and the United States. We find much higher socioeconomic segregation in large metropolitan areas in the United States than in France. We also find (1) a strong pattern of low-income neighborhoods in central cities and high-income neighborhoods in suburbs in the United States, but varying patterns across metropolitan areas in France; (2) that high-income persons are the most segregated group in both countries; (3) that the shares of neighborhood income differences that can be explained by neighborhood racial/ethnic composition are similar in France and the United States; and (4) that government-assisted housing is disproportionately located in the poorest neighborhoods in the United States but is spread across many neighborhood income levels in France. We conclude that differences in government provision of housing assistance and levels of income inequality are likely important contributing factors to the Franco-U.S. difference in socioeconomic segregation.

  18. Uses of AES and RGA to study neutron-irradiation-enhanced segregation to internal surfaces

    International Nuclear Information System (INIS)

    Gessel, G.R.; White, C.L.

    1980-01-01

    The high flux of point defects to sinks during neutron irradiation can result in segregation of impurity or alloy additions to metals. Such segregants can be preexisting or produced by neutron-induced transmutations. This segregation is known to strongly influence swelling and mechanical properties. Over a period of years, facilities have been developed at ORNL incorporating AES and RGA to examine irradiated materials. Capabilities of this system include in situ tensile fracture at elevated temperatures under ultrahigh vacuum 10 -10 torr and helium release monitoring. AES and normal incidence inert ion sputtering are exploited to examine segregation at the fracture surface and chemical gradients near the surface

  19. Operation of arc heating furnace on manufacturing gigantic ingots and segregation of gigantic ingots

    International Nuclear Information System (INIS)

    Niimi, Takayasu; Okamura, Masayoshi

    1976-01-01

    The techniques and procedure for manufacturing gigantic ingots heavier than 200 t are described. Especially, practical results of an arc heating furnace which plays an important role in the procedure and segregation of gigantic ingots are discussed in detail. By appropriate operations of the arc heating furnance, hydrogen and phosphorus are kept unchanged, and oxygen and sulphur decrease to very low levels. Furthermore, the temperature can be accurately controlled. The application of multipour technique reduces segregation and its degree is dependent on kinds of steel. V-segregation and inverted V-segregation in steel deoxidized with carbon in vacuum seem to be very slight. (auth.)

  20. Bulk ordering and surface segregation in Ni50Pt50

    DEFF Research Database (Denmark)

    Pourovskii, L.P.; Ruban, Andrei; Abrikosov, I.A.

    2001-01-01

    in the bulk compare well with experimental data. The surface-alloy compositions for the (111) and (110) facets above the ordering transition temperature are also found to be in a good agreement with experiments. It is demonstrated that the segregation profile at the (110) surface of NiPt is mainly caused...... by the unusually strong segregation of Pt into the second layer and the interlayer ordering due to large chemical nearest-neighbor interactions....

  1. Meiosis I chromosome segregation is established through regulation of microtubule–kinetochore interactions

    Science.gov (United States)

    Miller, Matthew P; Ünal, Elçin; Brar, Gloria A; Amon, Angelika

    2012-01-01

    During meiosis, a single round of DNA replication is followed by two consecutive rounds of nuclear divisions called meiosis I and meiosis II. In meiosis I, homologous chromosomes segregate, while sister chromatids remain together. Determining how this unusual chromosome segregation behavior is established is central to understanding germ cell development. Here we show that preventing microtubule–kinetochore interactions during premeiotic S phase and prophase I is essential for establishing the meiosis I chromosome segregation pattern. Premature interactions of kinetochores with microtubules transform meiosis I into a mitosis-like division by disrupting two key meiosis I events: coorientation of sister kinetochores and protection of centromeric cohesin removal from chromosomes. Furthermore we find that restricting outer kinetochore assembly contributes to preventing premature engagement of microtubules with kinetochores. We propose that inhibition of microtubule–kinetochore interactions during premeiotic S phase and prophase I is central to establishing the unique meiosis I chromosome segregation pattern. DOI: http://dx.doi.org/10.7554/eLife.00117.001 PMID:23275833

  2. Axial segregation of granular media rotated in a drum mixer: Pattern evolution

    International Nuclear Information System (INIS)

    Hill, K.M.; Kakalios, J.; Caprihan, A.

    1997-01-01

    In the traditional axial segregation effect, a homogeneous mixture of different types of granular material rotated in a drum mixer segregates into surface bands of relatively pure single concentrations along the axis of rotation. This effect primarily has been studied with respect to the initial segregation. However, the initial pattern is not stable, but evolves in time with continued rotation through metastable states of fewer and fewer bands. We describe two experimental studies of this evolution that provide a more complete picture of the dynamics involved in the pattern progression. The use of a charge coupled device camera in conjunction with digital analysis techniques provides a quantitative measure of the state of the surface as a function of time, while magnetic resonance imaging techniques provide a noninvasive method for studying the segregation beneath the surface. These methods indicate that the underlying mechanisms for the pattern evolution may originate in the bulk of the material, beneath the avalanching surface. copyright 1997 The American Physical Society

  3. Cardiac Calcium ATPase Dimerization Measured by Cross-Linking and Fluorescence Energy Transfer.

    Science.gov (United States)

    Blackwell, Daniel J; Zak, Taylor J; Robia, Seth L

    2016-09-20

    The cardiac sarco/endoplasmic reticulum calcium ATPase (SERCA) establishes the intracellular calcium gradient across the sarcoplasmic reticulum membrane. It has been proposed that SERCA forms homooligomers that increase the catalytic rate of calcium transport. We investigated SERCA dimerization in rabbit left ventricular myocytes using a photoactivatable cross-linker. Western blotting of cross-linked SERCA revealed higher-molecular-weight species consistent with SERCA oligomerization. Fluorescence resonance energy transfer measurements in cells transiently transfected with fluorescently labeled SERCA2a revealed that SERCA readily forms homodimers. These dimers formed in the absence or presence of the SERCA regulatory partner, phospholamban (PLB) and were unaltered by PLB phosphorylation or changes in calcium or ATP. Fluorescence lifetime data are compatible with a model in which PLB interacts with a SERCA homodimer in a stoichiometry of 1:2. Together, these results suggest that SERCA forms constitutive homodimers in live cells and that dimer formation is not modulated by SERCA conformational poise, PLB binding, or PLB phosphorylation. Copyright © 2016 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  4. Segregation of calcium signalling mechanisms in magnocellular neurones and terminals

    Czech Academy of Sciences Publication Activity Database

    Dayanithi, Govindan; Forostyak, Oksana; Ueta, Y.; Verkhratsky, Alexei; Toescu, E.C.

    2012-01-01

    Roč. 51, 3-4 (2012), s. 293-299 ISSN 0143-4160 R&D Projects: GA ČR(CZ) GAP303/11/0192 Institutional research plan: CEZ:AV0Z50390703 Keywords : Ca2+ stores * Mitochondria * Endoplasmic reticulum Subject RIV: FH - Neurology Impact factor: 4.327, year: 2012

  5. OCCUPATIONAL SEGREGATION BY GENDER - WHERE DOES ROMANIA STAND?

    Directory of Open Access Journals (Sweden)

    Manciu Venera

    2015-07-01

    Full Text Available The issue of occupational segregation is a topic discussed in the foreign economic literature, but on which documents written by Romanian authors are not so numerous. Still, during the last decades, this problem gained attention and began to preoccupy more individuals, especially on the basis of female emancipation process. In the past, various occupations were destined to be developed only by male employees. Women represent more than half of the overall population of the world. Even if prejudices on women are no longer as intense as they were in the past, and the access to education is widely open even in less-developed countries, consequently increasing the number of female workers, there are still several issues regarding occupational segregation and gender inequality that need to be solved. Today, many prejudices are lost, and female employees are more appreciated and manage to occupy traditional positions, as well as the ones that in the past were allocated only for the opposite gender. An assumption met in literature is that a rich country is able to confront more efficiently its problems and that the level of development should lower the gender gaps also. The purpose of this paper is to illustrate the situation of occupational segregation in Romania, through both theoretical and empirical methods. Still, the research is a qualitative one, considering that the available data is limited, at the present moment. The first part illustrates the concept of gender equality and occupational segregation, followed by an interpretation of the official data provided by the reports elaborated by the institutes in the field. The last part consist in a brief analysis of the relationship between the gender equality index and the economic growth, illustrated by the values of GDP.

  6. The acoustic and perceptual cues affecting melody segregation for listeners with a cochlear implant.

    Directory of Open Access Journals (Sweden)

    Jeremy eMarozeau

    2013-11-01

    Full Text Available Our ability to listen selectively to single sound sources in complex auditory environments is termed ‘auditory stream segregation.’ This ability is affected by peripheral disorders such as hearing loss, as well as plasticity in central processing such as occurs with musical training. Brain plasticity induced by musical training can enhance the ability to segregate sound, leading to improvements in a variety of auditory abilities. The melody segregation ability of 12 cochlear-implant recipients was tested using a new method to determine the perceptual distance needed to segregate a simple 4-note melody from a background of interleaved random-pitch distractor notes. In experiment 1, participants rated the difficulty of segregating the melody from distracter notes. Four physical properties of the distracter notes were changed. In experiment 2, listeners were asked to rate the dissimilarity between melody patterns whose notes differed on the four physical properties simultaneously. Multidimensional scaling analysis transformed the dissimilarity ratings into perceptual distances. Regression between physical and perceptual cues then derived the minimal perceptual distance needed to segregate the melody.The most efficient streaming cue for CI users was loudness. For the normal hearing listeners without musical backgrounds, a greater difference on the perceptual dimension correlated to the temporal envelope is needed for stream segregation in CI users. No differences in streaming efficiency were found between the perceptual dimensions linked to the F0 and the spectral envelope.Combined with our previous results in normally-hearing musicians and non-musicians, the results show that differences in training as well as differences in peripheral auditory processing (hearing impairment and the use of a hearing device influences the way that listeners use different acoustic cues for segregating interleaved musical streams.

  7. Study of solute segregation at interfaces using Auger electron spectroscopy

    International Nuclear Information System (INIS)

    White, C.L.

    1984-01-01

    Interfacial segregation, often confined to within a few atomic distances of the interface, can strongly influence the processing and properties of metals and ceramics. The thinness of such solute-enriched regions can cause them to be particularly suitable for study using surface sensitive microanalytical techniques such as Auger electron spectroscopy (AES). The application of AES to studies of interfacial segregation in metals and ceramics is briefly reviewed, and several examples are presented. 43 references, 14 figures

  8. Adsorption-Driven Surface Segregation of the Less Reactive Alloy Component

    DEFF Research Database (Denmark)

    Andersson, Klas Jerker; Calle Vallejo, Federico; Rossmeisl, Jan

    2009-01-01

    Counterintuitive to expectations and all prior observations of adsorbate-induced surface segregation of the more reactive alloy component (the one forming the stronger bond with the adsorbate), we show that CO adsorption at elevated pressures and temperatures pulls the less reactive Cu to the sur......Counterintuitive to expectations and all prior observations of adsorbate-induced surface segregation of the more reactive alloy component (the one forming the stronger bond with the adsorbate), we show that CO adsorption at elevated pressures and temperatures pulls the less reactive Cu...... to the surface of a CuPt near-surface alloy. The Cu surface segregation is driven by the formation of a stable self-organized CO/CuPt surface alloy structure and is rationalized in terms of the radically stronger Pt−CO bond when Cu is present in the first surface layer of Pt. The results, which are expected...

  9. Complex segregation analysis of craniomandibular osteopathy in Deutsch Drahthaar dogs.

    Science.gov (United States)

    Vagt, J; Distl, O

    2018-01-01

    This study investigated familial relationships among Deutsch Drahthaar dogs with craniomandibular osteopathy and examined the most likely mode of inheritance. Sixteen Deutsch Drahthaar dogs with craniomandibular osteopathy were diagnosed using clinical findings, radiography or computed tomography. All 16 dogs with craniomandibular osteopathy had one common ancestor. Complex segregation analyses rejected models explaining the segregation of craniomandibular osteopathy through random environmental variation, monogenic inheritance or an additive sex effect. Polygenic and mixed major gene models sufficiently explained the segregation of craniomandibular osteopathy in the pedigree analysis and offered the most likely hypotheses. The SLC37A2:c.1332C>T variant was not found in a sample of Deutsch Drahthaar dogs with craniomandibular osteopathy, nor in healthy controls. Craniomandibular osteopathy is an inherited condition in Deutsch Drahthaar dogs and the inheritance seems to be more complex than a simple Mendelian model. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Endurance training in the spontaneously hypertensive rat: conversion of pathological into physiological cardiac hypertrophy.

    Science.gov (United States)

    Garciarena, Carolina D; Pinilla, Oscar A; Nolly, Mariela B; Laguens, Ruben P; Escudero, Eduardo M; Cingolani, Horacio E; Ennis, Irene L

    2009-04-01

    The effect of endurance training (swimming 90 min/d for 5 days a week for 60 days) on cardiac hypertrophy was investigated in the spontaneously hypertensive rat (SHR). Sedentary SHRs (SHR-Cs) and normotensive Wistar rats were used as controls. Exercise training enhanced myocardial hypertrophy assessed by left ventricular weight/tibial length (228+/-7 versus 251+/-5 mg/cm in SHR-Cs and exercised SHRs [SHR-Es], respectively). Myocyte cross-sectional area increased approximately 40%, collagen volume fraction decreased approximately 50%, and capillary density increased approximately 45% in SHR-Es compared with SHR-Cs. The mRNA abundance of atrial natriuretic factor and myosin light chain 2 was decreased by the swimming routine (100+/-19% versus 41+/-10% and 100+/-8% versus 61+/-9% for atrial natriuretic factor and myosin light chain 2 in SHR-Cs and SHR-Es, respectively). The expression of sarcoplasmic reticulum Ca(2+) pump was significantly augmented, whereas that of Na(+)/Ca(2+) exchanger was unchanged (93+/-7% versus 167+/-8% and 158+/-13% versus 157+/-7%, sarcoplasmic reticulum Ca(2+) pump and Na(+)/Ca(2+) exchanger in SHR-Cs and SHR-Es, respectively; PEndurance training inhibited apoptosis, as reflected by a decrease in caspase 3 activation and poly(ADP-ribose) polymerase-1 cleavage, and normalized calcineurin activity without inducing significant changes in the phosphatidylinositol 3-kinase/Akt pathway. The swimming routine improved midventricular shortening determined by echocardiography (32.4+/-0.9% versus 36.9+/-1.1% in SHR-Cs and SHR-Es, respectively; Pendurance training to convert pathological into physiological hypertrophy improving cardiac performance. The reduction of myocardial fibrosis and calcineurin activity plus the increase in capillary density represent factors to be considered in determining this beneficial effect.

  11. Cholesterol Removal from Adult Skeletal Muscle impairs Excitation-Contraction Coupling and Aging reduces Caveolin-3 and alters the Expression of other Triadic Proteins

    Directory of Open Access Journals (Sweden)

    Genaro eBarrientos

    2015-04-01

    Full Text Available Cholesterol and caveolin are integral membrane components that modulate the function/location of many cellular proteins. Skeletal muscle fibers, which have unusually high cholesterol levels in transverse tubules, express the caveolin-3 isoform but its association with transverse tubules remains contentious. Cholesterol removal impairs excitation-contraction coupling in amphibian and mammalian fetal skeletal muscle fibers. Here, we show that treating single muscle fibers from adult mice with the cholesterol removing agent methyl-β-cyclodextrin decreased fiber cholesterol by 26%, altered the location pattern of caveolin-3 and of the voltage dependent calcium channel Cav1.1, and suppressed or reduced electrically evoked Ca2+ transients without affecting membrane integrity or causing sarcoplasmic reticulum calcium depletion. We found that transverse tubules from adult muscle and triad fractions that contain ~10% attached transverse tubules, but not sarcoplasmic reticulum membranes, contained caveolin-3 and Cav1.1; both proteins partitioned into detergent-resistant membrane fractions highly enriched in cholesterol. Aging entails significant deterioration of skeletal muscle function. We found that triad fractions from aged rats had similar cholesterol and RyR1 protein levels compared to triads from young rats, but had lower caveolin-3 and glyceraldehyde 3-phosphate dehydrogenase and increased Na+/K+-ATPase protein levels. Both triad fractions had comparable NADPH oxidase (NOX activity and protein content of NOX2 subunits (p47phox and gp91phox, implying that NOX activity does not increase during aging. These findings show that partial cholesterol removal impairs excitation-contraction coupling and alters caveolin-3 and Cav1.1 location pattern, and that aging reduces caveolin-3 protein content and modifies the expression of other triadic proteins. We discuss the possible implications of these findings for skeletal muscle function in young and aged

  12. Role of calpain in eccentric contraction-induced proteolysis of Ca2+-regulatory proteins and force depression in rat fast-twitch skeletal muscle.

    Science.gov (United States)

    Kanzaki, Keita; Watanabe, Daiki; Kuratani, Mai; Yamada, Takashi; Matsunaga, Satoshi; Wada, Masanobu

    2017-02-01

    The aim of this study was to examine the in vivo effects of eccentric contraction (ECC) on calpain-dependent proteolysis of Ca 2+ -regulatory proteins and force production in fast-twitch skeletal muscles. Rat extensor digitorum longus muscles were exposed to 200 repeated ECC in situ and excised immediately [recovery 0 (REC0)] or 3 days [recovery 3 (REC3)] after cessation of ECC. Calpain inhibitor (CI)-treated rats were intraperitoneally injected with MDL-28170 before ECC and during REC3. Tetanic force was markedly reduced at REC0 and remained reduced at REC3. CI treatment ameliorated the ECC-induced force decline but only at REC3. No evidence was found for proteolysis of dihydropyridine receptor (DHPR), junctophilin (JP)1, JP2, ryanodine receptor (RyR), sarcoplasmic reticulum Ca 2+ -ATPase (SERCA)1a, or junctional face protein-45 at REC0. At REC3, ECC resulted in decreases in DHPR, JP1, JP2, RyR, and SERCA1a. CI treatment prevented the decreases in DHPR, JP1, and JP2, whereas it had little effect on RyR and SERCA1a. These findings suggest that DHPR, JP1, and JP2, but not RyR and SERCA1a, undergo calpain-dependent proteolysis in in vivo muscles subjected to ECC and that impaired function of DHPR and/or JP might cause prolonged force deficits with ECC. NEW & NOTEWORTHY Calpain-dependent proteolysis is one of the contributing factors to muscle damage that occurs with eccentric contraction (ECC). It is unclear, however, whether calpains account for proteolysis of Ca 2+ -regulatory proteins in in vivo muscles subjected to ECC. Here, we provide evidence that dihydropyridine receptor and junctophilin, but not ryanodine receptor and sarcoplasmic reticulum Ca 2+ -ATPase, undergo calpain-dependent proteolysis. Copyright © 2017 the American Physiological Society.

  13. Preservation of the positive lusitropic effect of beta-adrenoceptors stimulation in diabetic cardiomyopathy.

    Science.gov (United States)

    Amour, Julien; Loyer, Xavier; Michelet, Pierre; Birenbaum, Aurélie; Riou, Bruno; Heymes, Christophe

    2008-10-01

    In diabetic cardiomyopathy, diastolic dysfunction results in part from sarcoplasmic reticulum abnormalities affecting both phospholamban and sarcoplasmic reticulum Ca2+ uptake (SERCA2a). Consequently, the positive lusitropic effect of beta-adrenoceptors stimulation could be altered, and beta3-adrenoceptor over-expression may play a role, as previously demonstrated with an altered positive inotropic effect. In this study, we tested the hypothesis that the beta-adrenergic positive lusitropic effect is altered in diabetic cardiomyopathy, and that beta3-adrenoceptor over-expression is involved. beta-adrenergic responses were investigated in vivo (dobutamine-echocardiography) and in vitro (papillary muscle preparation) in healthy and diabetic rats killed 4 (4W) and 12 (12W) wk after IV streptozotocin injection. The effect of beta3-adrenoceptor pathway inhibition by S-cyanopindolol (selective beta3-adrenoceptor antagonist) or by NG-nitro-L-arginine-methyl-ester (nonselective nitric oxide synthase inhibitor) on the lusitropic response to isoproterenol (nonselective beta-adrenoceptors agonist) was studied in vitro. Western blots were performed to quantify the protein expressions of beta1- and beta3-adrenoceptors, phospholamban, and SERCA2a. Data are presented as mean percentages of baseline+/-sd. Despite the increased phospholamban/SERCA2a protein ratio and documented diastolic dysfunction, the positive lusitropic effect of beta-adrenoceptors stimulation was preserved in vivo (dobutamine) and in vitro (isoproterenol) in 4W and 12W diabetic, compared with healthy, rats. The beta3-adrenoceptor was up-regulated whereas beta1-adrenoceptor was down-regulated in 4W and 12W diabetic, compared with healthy, rats. Nevertheless, S-cyanopindolol or NG-nitro-L-arginine-methyl-ester had no lusitropic effect. The positive lusitropic effect of beta-adrenoceptor stimulation was preserved in diabetic cardiomyopathy. beta3-adrenoceptor over-expression does not seem to affect this process.

  14. Development of porcine model of chronic tachycardia-induced cardiomyopathy.

    Science.gov (United States)

    Paslawska, Urszula; Gajek, Jacek; Kiczak, Liliana; Noszczyk-Nowak, Agnieszka; Skrzypczak, Piotr; Bania, Jacek; Tomaszek, Alicja; Zacharski, Maciej; Sambor, Izabela; Dziegiel, Piotr; Zysko, Dorota; Banasiak, Waldemar; Jankowska, Ewa A; Ponikowski, Piotr

    2011-11-17

    There are few experimental models of heart failure (HF) in large animals, despite structural and functional similarities to human myocardium. We have developed a porcine model of chronic tachycardia-induced cardiomyopathy. Homogenous siblings of White Large breed swine (n=6) underwent continuous right ventricular (RV) pacing at 170 bpm; 2 subjects served as controls. In the course of RV pacing, animals developed a clinical picture of HF and were presented for euthanasia at subsequent stages: mild, moderate and end-stage HF. Left ventricle (LV) sections were analyzed histologically and relative ANP, BNP, phospholamban and sarcoplasmic reticulum calcium ATPase 2a transcript levels in LV were quantified by real time RT-PCR. In the course of RV pacing, animals demonstrated reduced exercise capacity (time of running until being dyspnoeic: 6.6 ± 0.5 vs. 2.4 ± 1.4 min), LV dilatation (LVEDD: 4.9 ± 0.4 vs. 6.7 ± 0.4 cm), impaired LV systolic function (LVEF: 69 ± 8 vs. 32 ± 7 %), (all baseline vs. before euthanasia, all p<0.001). LV tissues from animals with moderate and end-stage HF demonstrated local foci of interstitial fibrosis, congestion, cardiomyocyte hypertrophy and atrophy, which was not detected in controls and mild HF animals. The up-regulation of ANP and BNP and a reduction in a ratio of sarcoplasmic reticulum calcium ATPase 2a and phospholamban in failing myocardium were observed as compared to controls. In pigs, chronic RV pacing at relatively low rate can be used as an experimental model of HF, as it results in a gradual deterioration of exercise tolerance accompanied by myocardial remodeling confirmed at subcellular level. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  15. Silica segregation in the Ni/YSZ electrode

    DEFF Research Database (Denmark)

    Hauch, Anne; Jensen, Søren Højgaard; Bilde-Sørensen, Jørgen

    2007-01-01

    . These postmortem analyses reveal the reason for the observed passivation, because results from energy-dispersive spectroscopy clearly show evidence that silica-containing impurities have segregated to the hydrogen electrode/electrolyte interface during electrolysis testing. Examples of different microstructures...

  16. THE RESPONSE OF DISSEMINATED RETICULUM CELL SARCOMA TO THE INTRAVENOUS INJECTION OF COLLOIDAL RADIOACTIVE GOLD

    Energy Technology Data Exchange (ETDEWEB)

    Rubin, Philip; Levitt, Seymour H.

    1963-06-15

    Case histories of two patients treated with colloidal radiogold for diffuse reticulum cell sarcoma are presented. Further analysis of the method is suggested by the unusually long survival time of one of the patients. It was concluded that, although external radiotherapy remains the treatment of choice in localized reticulum cell sarcoma, intravenous colloidal radiogold may be a useful agent in lymphosarcomas with diffuse minute neoplastic liver and spleen involvements. Intravenous colloidal radiogold can produce bone marrow depression and thrombocytopenia which can lead to death. This factor tends to argue against therapeutic use of the agent. It is suggested that no more than 50 mC Au/sup 198/ intravenously should be used for treatment of this disease. (R.M.G.)

  17. Methods for monitoring endoplasmic reticulum stress and the unfolded protein response.

    LENUS (Irish Health Repository)

    Samali, Afshin

    2010-01-01

    The endoplasmic reticulum (ER) is the site of folding of membrane and secreted proteins in the cell. Physiological or pathological processes that disturb protein folding in the endoplasmic reticulum cause ER stress and activate a set of signaling pathways termed the Unfolded Protein Response (UPR). The UPR can promote cellular repair and sustained survival by reducing the load of unfolded proteins through upregulation of chaperones and global attenuation of protein synthesis. Research into ER stress and the UPR continues to grow at a rapid rate as many new investigators are entering the field. There are also many researchers not working directly on ER stress, but who wish to determine whether this response is activated in the system they are studying: thus, it is important to list a standard set of criteria for monitoring UPR in different model systems. Here, we discuss approaches that can be used by researchers to plan and interpret experiments aimed at evaluating whether the UPR and related processes are activated. We would like to emphasize that no individual assay is guaranteed to be the most appropriate one in every situation and strongly recommend the use of multiple assays to verify UPR activation.

  18. Methods for Monitoring Endoplasmic Reticulum Stress and the Unfolded Protein Response

    Directory of Open Access Journals (Sweden)

    Afshin Samali

    2010-01-01

    Full Text Available The endoplasmic reticulum (ER is the site of folding of membrane and secreted proteins in the cell. Physiological or pathological processes that disturb protein folding in the endoplasmic reticulum cause ER stress and activate a set of signaling pathways termed the Unfolded Protein Response (UPR. The UPR can promote cellular repair and sustained survival by reducing the load of unfolded proteins through upregulation of chaperones and global attenuation of protein synthesis. Research into ER stress and the UPR continues to grow at a rapid rate as many new investigators are entering the field. There are also many researchers not working directly on ER stress, but who wish to determine whether this response is activated in the system they are studying: thus, it is important to list a standard set of criteria for monitoring UPR in different model systems. Here, we discuss approaches that can be used by researchers to plan and interpret experiments aimed at evaluating whether the UPR and related processes are activated. We would like to emphasize that no individual assay is guaranteed to be the most appropriate one in every situation and strongly recommend the use of multiple assays to verify UPR activation.

  19. Improved polymer thin-film wetting behavior through nanoparticle segregation to interfaces

    International Nuclear Information System (INIS)

    Krishnan, R S; Mackay, M E; Duxbury, P M; Hawker, C J; Asokan, Suba; Wong, Michael S; Goyette, Rick; Thiyagarajan, P

    2007-01-01

    We report a systematic study of improved wetting behavior for thin polymer films containing nanoparticles, as a function of nanoparticle size and concentration, the energy of the substrate and the dielectric properties of the nanoparticles. An enthalpy matched system consisting of polystyrene nanoparticles in linear polystyrene is used to show that nanoparticles are uniformly distributed in the film after spin coating and drying. However, on annealing the film above its bulk glass transition temperature these nanoparticles segregate strongly to the solid substrate. We find that for a wide range of film thicknesses and nanoparticle sizes, a substrate coverage of nanoparticles of approximately a monolayer is required for dewetting inhibition. Cadmium selenide quantum dots also inhibit dewetting of polystyrene thin films, again when a monolayer is present. Moreover, TEM microscopy images indicate that CdSe quantum dots segregate primarily to the air interface. Theoretical interpretation of these phenomena suggests that gain of linear chain configurational entropy promotes segregation of nanoparticles to the solid substrate, as occurs for polystyrene nanoparticles; however, for CdSe nanoparticles this is offset by surface energy or enthalpic terms which promote segregation of the nanoparticles to the air interface

  20. Concurrent Speech Segregation Problems in Hearing Impaired Children

    Directory of Open Access Journals (Sweden)

    Hossein Talebi

    2014-04-01

    Full Text Available Objective: This study was a basic investigation of the ability of concurrent speech segregation in hearing impaired children. Concurrent segregation is one of the fundamental components of auditory scene analysis and plays an important role in speech perception. In the present study, we compared auditory late responses or ALRs between hearing impaired and normal children. Materials & Methods: Auditory late potentials in response to 12 double vowels were recorded in 10 children with moderate to severe sensory neural hearing loss and 10 normal children. Double vowels (pairs of synthetic vowels were presented concurrently and binaurally. Fundamental frequency (F0 of these vowels and the size of the difference in F0 between vowels was 100 Hz and 0.5 semitones respectively. Results: Comparing N1-P2 amplitude showed statistically significant difference in some stimuli between hearing impaired and normal children (P<0.05. This complex indexing the vowel change detection and reflecting central auditory speech representation without active client participation was decreased in hearing impaired children. Conclusion: This study showed problems in concurrent speech segregation in hearing impaired children evidenced by ALRs. This information indicated deficiencies in bottom-up processing of speech characteristics based on F0 and its differences in these children.

  1. Temperature dependence of cardiac sarcoplasmic reticulum and sarcolemma in the ventricle of catfish (Clarias gariepinus

    Directory of Open Access Journals (Sweden)

    El-Sabry Abu-Amra

    2015-10-01

    The sarcolemmal Ca2+ contribution of activator Ca2+ was greater at a test temperature of 30 °C as assessed by verapamil. Whereas the SR-Ca2+ contribution was higher at 20 and 30 °C and a frequency rate of 0.2 and 0.4 Hz as assessed by caffeine and adrenaline, respectively. Bradykinin potentiating factor (BPF7 which was isolated from jelly fish (Cassiopea andromeda decreased the cardiac force developed at a frequency rate of 0.2 Hz and a temperature of 20 °C, whereas it increased the force developed at frequency rates of 0.2 and 0.4 Hz at 30 °C. These results indicate that BPF7 may act like verapamil in reducing the cardiac force through blocking the sarcolemmal Ca2+ channels at low temperature and like adrenaline in an increase of the cardiac force developed at warm temperature and the high frequency rate through stimulation of SR-Ca2+ activator. Therefore, this study indicates that the sarcolemmal Ca2+ influx and the SR-Ca2+ release contributors of activator Ca2+ for cardiac force development in the catfish heart were significantly greater at warm temperature and at the pacing frequency rates of 0.2 and 0.4 Hz as assessed by verapamil, adrenaline, caffeine and BPF7. However, the relative contribution of the sarcolemmal Ca2+ influx in the development of cardiac force in the catfish heart was greater than that of SR-Ca2+ release.

  2. Endoplasmic Reticulum-Plasma Membrane Contact Sites.

    Science.gov (United States)

    Saheki, Yasunori; De Camilli, Pietro

    2017-06-20

    The endoplasmic reticulum (ER) has a broad localization throughout the cell and forms direct physical contacts with all other classes of membranous organelles, including the plasma membrane (PM). A number of protein tethers that mediate these contacts have been identified, and study of these protein tethers has revealed a multiplicity of roles in cell physiology, including regulation of intracellular Ca 2+ dynamics and signaling as well as control of lipid traffic and homeostasis. In this review, we discuss the cross talk between the ER and the PM mediated by direct contacts. We review factors that tether the two membranes, their properties, and their dynamics in response to the functional state of the cell. We focus in particular on the role of ER-PM contacts in nonvesicular lipid transport between the two bilayers mediated by lipid transfer proteins.

  3. Nuclear envelope expansion is crucial for proper chromosomal segregation during a closed mitosis.

    Science.gov (United States)

    Takemoto, Ai; Kawashima, Shigehiro A; Li, Juan-Juan; Jeffery, Linda; Yamatsugu, Kenzo; Elemento, Olivier; Nurse, Paul

    2016-03-15

    Here, we screened a 10,371 library of diverse molecules using a drug-sensitive fission yeast strain to identify compounds which cause defects in chromosome segregation during mitosis. We identified a phosphorium-ylide-based compound Cutin-1 which inhibits nuclear envelope expansion and nuclear elongation during the closed mitosis of fission yeast, and showed that its target is the β-subunit of fatty acid synthase. A point mutation in the dehydratase domain of Fas1 conferred in vivo and in vitro resistance to Cutin-1. Time-lapse photomicrography showed that the bulk of the chromosomes were only transiently separated during mitosis, and nucleoli separation was defective. Subsequently sister chromatids re-associated leading to chromosomal mis-segregation. These segregation defects were reduced when the nuclear volume was increased and were increased when the nuclear volume was reduced. We propose that there needs to be sufficient nuclear volume to allow the nuclear elongation necessary during a closed mitosis to take place for proper chromosome segregation, and that inhibition of fatty acid synthase compromises nuclear elongation and leads to defects in chromosomal segregation. © 2016. Published by The Company of Biologists Ltd.

  4. Should Educators and Parents Encourage Other-Gender Interactions? Gender Segregation and Sexism

    Science.gov (United States)

    Keener, Emily; Mehta, Clare; Strough, JoNell

    2013-01-01

    We investigated gender differences in the association between gender-segregated peer preferences and sexism in adolescents (15-17 years, 60 boys and 85 girls). To assess gender-segregated peer preferences, adolescents nominated peers for interaction in two contexts: "hanging out" at home and working on a school project. The Modern Sexism…

  5. Rayleigh Number Criterion for Formation of A-Segregates in Steel Castings and Ingots

    DEFF Research Database (Denmark)

    Rad, M. Torabi; Kotas, Petr; Beckermann, C.

    2013-01-01

    A Rayleigh number-based criterion is developed for predicting the formation of A-segregates in steel castings and ingots. The criterion is calibrated using available experimental data for ingots involving 27 different steel compositions. The critical Rayleigh number above which A-segregates can b......, the primary reason for this over-prediction is persumed to be the presence of a central zone of equiaxed grains in the casting sections. A-segregates do not form when the grain structure is equiaxed. © The Minerals, Metals & Materials Society and ASM International 2013...

  6. Influence of the primary recoil spectrum on radiation-induced segregation in nickel-silicon

    International Nuclear Information System (INIS)

    Averback, R.S.; Rehn, L.E.; Wiedersich, H.; Cook, R.E.

    1980-01-01

    Radiation induced segregation in Ni-12.7% Si has been examined for 1.5 MeV He, 2.0 MeV Li, and 2.75 MeV Kr irradiations. A method to simultaneously damage and analyze the specimens during light-ion irradiation is described. The amount of segregation was determined by using Rutherford backscattering spectrometry to measure the thickness of the γ' layer which develops at the surface. Substantially less segregation of Si to the surface is observed for the Kr irradiation than for the light-ion irradiations at 520 0 C

  7. Effects of segregation of primary alloying elements on the creep response in magnesium alloys

    DEFF Research Database (Denmark)

    Huang, Y.D.; Dieringa, H.; Hort, N.

    2008-01-01

    The segregation of primary alloying elements deteriorates the high temperature creep resistance of magnesium alloys. Annealing at high temperatures alleviating their segregations can improve the creep resistance. Present investigation on the effect of segregation of primary alloying elements...... on the creep response may provide some useful information about how to improve the creep resistance of magnesium alloys in the future. (c) 2008 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved....

  8. Brain network segregation and integration during an epoch-related working memory fMRI experiment.

    Science.gov (United States)

    Fransson, Peter; Schiffler, Björn C; Thompson, William Hedley

    2018-05-17

    The characterization of brain subnetwork segregation and integration has previously focused on changes that are detectable at the level of entire sessions or epochs of imaging data. In this study, we applied time-varying functional connectivity analysis together with temporal network theory to calculate point-by-point estimates in subnetwork segregation and integration during an epoch-based (2-back, 0-back, baseline) working memory fMRI experiment as well as during resting-state. This approach allowed us to follow task-related changes in subnetwork segregation and integration at a high temporal resolution. At a global level, the cognitively more taxing 2-back epochs elicited an overall stronger response of integration between subnetworks compared to the 0-back epochs. Moreover, the visual, sensorimotor and fronto-parietal subnetworks displayed characteristic and distinct temporal profiles of segregation and integration during the 0- and 2-back epochs. During the interspersed epochs of baseline, several subnetworks, including the visual, fronto-parietal, cingulo-opercular and dorsal attention subnetworks showed pronounced increases in segregation. Using a drift diffusion model we show that the response time for the 2-back trials are correlated with integration for the fronto-parietal subnetwork and correlated with segregation for the visual subnetwork. Our results elucidate the fast-evolving events with regard to subnetwork integration and segregation that occur in an epoch-related task fMRI experiment. Our findings suggest that minute changes in subnetwork integration are of importance for task performance. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  9. Strand-seq: A unifying tool for studies of chromosome segregation

    OpenAIRE

    Falconer, Ester; Lansdorp, Peter M.

    2013-01-01

    Non random segregation of sister chromatids has been implicated to help specify daughter cell fate (the Silent Sister Hypothesis [1]) or to protect the genome of long-lived stem cells (the Immortal Strand Hypothesis [2]). The idea that sister chromatids are non-randomly segregated into specific daughter cells is only marginally supported by data in sporadic and often contradictory studies. As a result, the field has moved forward rather slowly. The advent of being able to directly label and d...

  10. Linking urban sprawl and income segregation : findings from a stylized agent-based model

    NARCIS (Netherlands)

    Guo, C.; Buchmann, C.M.; Schwarz, N.

    2017-01-01

    Urban sprawl and income segregation are two undesired urban patterns that occur during urban development. Empirical studies show that income level and inequality are positively correlated with urban sprawl and income segregation, respectively. However, the relationship between urban sprawl and

  11. The pedogeochemical segregation a few horizons in soils from glass houses

    Science.gov (United States)

    Bulgariu, Dumitru; Rusu, Constantin; Filipov, Feodor; Buzgar, Nicolae; Bulgariu, Laura

    2010-05-01

    Our studies have focused the apparition and manifestation conditions of pedogeochemical segregation phenomena in case of soils from Copou - Iaşi, Bacău and Bârlad (Romania) glass house, and the effects of this on the pedogeochemical and agrochemical characteristics of soils from glass houses cultivated with vegetables. The utilization of intensive cultivation technologies of vegetables in glass houses determined the degradation of morphological, physical and chemical characteristics of soils, by rapid evolution of salted processes (salinization and / or sodization), compaction, carbonatation, eluviation-illuviation, frangipane formation, stagnogleization, gleization etc. Under these conditions, at depth of 30-40 cm is formed a compact and impenetrable horizon - Ahok(x) horizon. In function of exploitation conditions and by the chemical-mineralogical characteristics of soils from glasshouses, the Ahok horizons can have frangipane properties, expressed more or less. These horizons determined a geochemical segregation of soils from glass houses: (i) superior horizons, above Ahok(x) horizon evolve in weak oxidative conditions, weak alkaline pH, higher salinity, humidity and temperature; (ii) inferior horizons, below Ahok(x) horizon evolve in weak reducing conditions weak acid pH, lower salinity, humidity and temperature. Concomitant with the development of Ahok(x) horizons, the rapid degradation of the properties of soils from glasshouses is observed. The aspects about the formation of frangipane horizon in soils from glasshouses are not yet sufficiently know. Whatever of the formation processes, the frangipane horizons determined a sever segregation in pedogeochemical evolution of soils from glass houses, with very important consequences on the agrochemical quality of these soils. The segregation effects are manifested in the differential dynamics of pedogeochemical processes from superior horizons (situated above the segregation horizon), in comparison with the

  12. Segregation and persistence of form in the lateral occipital complex.

    Science.gov (United States)

    Ferber, Susanne; Humphrey, G Keith; Vilis, Tutis

    2005-01-01

    While the lateral occipital complex (LOC) has been shown to be implicated in object recognition, it is unclear whether this brain area is responsive to low-level stimulus-driven features or high-level representational processes. We used scrambled shape-from-motion displays to disambiguate the presence of contours from figure-ground segregation and to measure the strength of the binding process for shapes without contours. We found persisting brain activation in the LOC for scrambled displays after the motion stopped indicating that this brain area subserves and maintains figure-ground segregation processes, a low-level function in the object processing hierarchy. In our second experiment, we found that the figure-ground segregation process has some form of spatial constancy indicating top-down influences. The persisting activation after the motion stops suggests an intermediate role in object recognition processes for this brain area and might provide further evidence for the idea that the lateral occipital complex subserves mnemonic functions mediating between iconic and short-term memory.

  13. Solute partitioning and interfacial segregation in TiAl-based alloys

    International Nuclear Information System (INIS)

    Larson, D.J.; Miller, M.K.

    1999-01-01

    Atom probe microscopy has been used to investigate elemental partitioning and segregation behavior in a TiAl-based alloy with a variety of alloying additions including Cr, Nb, W and B. These results indicate that in a stress-relieved state (2h at 900 C) and a reheated state (2h at 900 C, 2,184h at 800 C and 2h at 1,210 C) chromium, and to a lesser extent tungsten, is partitioned to the α 2 phase. However, in an annealed state (2h at 900 C and 720 h at 800 C), these elements are partitioned to the γ phase. Segregation of chromium and tungsten to lamellar interfaces is observed in the stress-relieved material, but significant segregation was not observed in material subjected to the other heat treatments. A W- and B-enriched precipitate was observed in the reheated material and provides a possible explanation for the low tungsten concentrations measured in the matrix phases

  14. DEM Simulation of Particle Stratification and Segregation in Stockpile Formation

    Directory of Open Access Journals (Sweden)

    Zhang Dizhe

    2017-01-01

    Full Text Available Granular stockpiles are commonly observed in nature and industry, and their formation has been extensively investigated experimentally and mathematically in the literature. One of the striking features affecting properties of stockpiles are the internal patterns formed by the stratification and segregation processes. In this work, we conduct a numerical study based on DEM (discrete element method model to study the influencing factors and triggering mechanisms of these two phenomena. With the use of a previously developed mixing index, the effects of parameters including size ratio, injection height and mass ratio are investigated. We found that it is a void-filling mechanism that differentiates the motions of particles with different sizes. This mechanism drives the large particles to flow over the pile surface and segregate at the pile bottom, while it also pushes small particles to fill the voids between large particles, giving rise to separate layers. Consequently, this difference in motion will result in the observed stratification and segregation phenomena.

  15. Lipid Droplet Formation Is Dispensable for Endoplasmic Reticulum-associated Degradation*

    OpenAIRE

    Olzmann, James A.; Kopito, Ron R.

    2011-01-01

    Proteins that fail to fold or assemble in the endoplasmic reticulum (ER) are destroyed by cytoplasmic proteasomes through a process known as ER-associated degradation. Substrates of this pathway are initially sequestered within the ER lumen and must therefore be dislocated across the ER membrane to be degraded. It has been proposed that generation of bicellar structures during lipid droplet formation may provide an “escape hatch” through which misfolded proteins, toxins, and viruses can exit ...

  16. First-principles study of the effects of segregated Ga on an Al grain boundary

    International Nuclear Information System (INIS)

    Zhang Ying; Lu Guanghong; Wang Tianmin; Deng Shenghua; Shu Xiaolin; Kohyama, Masanori; Yamamoto, Ryoichi

    2006-01-01

    The effects of different amounts of segregated Ga (substitutional) on an Al grain boundary have been investigated by using a first-principles pseudopotential method. The segregated Ga is found to draw charge from the surrounding Al due to the electronegativity difference between Ga and Al, leading to a charge density reduction between Ga and Al as well as along the Al grain boundary. Such an effect can be enhanced by increasing the Ga segregation amount. With further Ga segregated, in addition to the charge-drawing effect that occurs in the Al-Ga interface, a heterogeneous α-Ga-like phase can form in the grain boundary, which greatly alters the boundary structure. These effects are suggested to be responsible for Ga-induced Al intergranular embrittlement

  17. Endoplasmic reticulum: ER stress regulates mitochondrial bioenergetics

    Science.gov (United States)

    Bravo, Roberto; Gutierrez, Tomás; Paredes, Felipe; Gatica, Damián; Rodriguez, Andrea E.; Pedrozo, Zully; Chiong, Mario; Parra, Valentina; Quest, Andrew F.G.; Rothermel, Beverly A.; Lavandero, Sergio

    2014-01-01

    Endoplasmic reticulum (ER) stress activates an adaptive unfolded protein response (UPR) that facilitates cellular repair, however, under prolonged ER stress, the UPR can ultimately trigger apoptosis thereby terminating damaged cells. The molecular mechanisms responsible for execution of the cell death program are relatively well characterized, but the metabolic events taking place during the adaptive phase of ER stress remain largely undefined. Here we discuss emerging evidence regarding the metabolic changes that occur during the onset of ER stress and how ER influences mitochondrial function through mechanisms involving calcium transfer, thereby facilitating cellular adaptation. Finally, we highlight how dysregulation of ER–mitochondrial calcium homeostasis during prolonged ER stress is emerging as a novel mechanism implicated in the onset of metabolic disorders. PMID:22064245

  18. Segregation and integration of auditory streams when listening to multi-part music.

    Directory of Open Access Journals (Sweden)

    Marie Ragert

    Full Text Available In our daily lives, auditory stream segregation allows us to differentiate concurrent sound sources and to make sense of the scene we are experiencing. However, a combination of segregation and the concurrent integration of auditory streams is necessary in order to analyze the relationship between streams and thus perceive a coherent auditory scene. The present functional magnetic resonance imaging study investigates the relative role and neural underpinnings of these listening strategies in multi-part musical stimuli. We compare a real human performance of a piano duet and a synthetic stimulus of the same duet in a prioritized integrative attention paradigm that required the simultaneous segregation and integration of auditory streams. In so doing, we manipulate the degree to which the attended part of the duet led either structurally (attend melody vs. attend accompaniment or temporally (asynchronies vs. no asynchronies between parts, and thus the relative contributions of integration and segregation used to make an assessment of the leader-follower relationship. We show that perceptually the relationship between parts is biased towards the conventional structural hierarchy in western music in which the melody generally dominates (leads the accompaniment. Moreover, the assessment varies as a function of both cognitive load, as shown through difficulty ratings and the interaction of the temporal and the structural relationship factors. Neurally, we see that the temporal relationship between parts, as one important cue for stream segregation, revealed distinct neural activity in the planum temporale. By contrast, integration used when listening to both the temporally separated performance stimulus and the temporally fused synthetic stimulus resulted in activation of the intraparietal sulcus. These results support the hypothesis that the planum temporale and IPS are key structures underlying the mechanisms of segregation and integration of

  19. Segregation and integration of auditory streams when listening to multi-part music.

    Science.gov (United States)

    Ragert, Marie; Fairhurst, Merle T; Keller, Peter E

    2014-01-01

    In our daily lives, auditory stream segregation allows us to differentiate concurrent sound sources and to make sense of the scene we are experiencing. However, a combination of segregation and the concurrent integration of auditory streams is necessary in order to analyze the relationship between streams and thus perceive a coherent auditory scene. The present functional magnetic resonance imaging study investigates the relative role and neural underpinnings of these listening strategies in multi-part musical stimuli. We compare a real human performance of a piano duet and a synthetic stimulus of the same duet in a prioritized integrative attention paradigm that required the simultaneous segregation and integration of auditory streams. In so doing, we manipulate the degree to which the attended part of the duet led either structurally (attend melody vs. attend accompaniment) or temporally (asynchronies vs. no asynchronies between parts), and thus the relative contributions of integration and segregation used to make an assessment of the leader-follower relationship. We show that perceptually the relationship between parts is biased towards the conventional structural hierarchy in western music in which the melody generally dominates (leads) the accompaniment. Moreover, the assessment varies as a function of both cognitive load, as shown through difficulty ratings and the interaction of the temporal and the structural relationship factors. Neurally, we see that the temporal relationship between parts, as one important cue for stream segregation, revealed distinct neural activity in the planum temporale. By contrast, integration used when listening to both the temporally separated performance stimulus and the temporally fused synthetic stimulus resulted in activation of the intraparietal sulcus. These results support the hypothesis that the planum temporale and IPS are key structures underlying the mechanisms of segregation and integration of auditory streams

  20. Digital morphogenesis via Schelling segregation

    Science.gov (United States)

    Barmpalias, George; Elwes, Richard; Lewis-Pye, Andrew

    2018-04-01

    Schelling’s model of segregation looks to explain the way in which particles or agents of two types may come to arrange themselves spatially into configurations consisting of large homogeneous clusters, i.e. connected regions consisting of only one type. As one of the earliest agent based models studied by economists and perhaps the most famous model of self-organising behaviour, it also has direct links to areas at the interface between computer science and statistical mechanics, such as the Ising model and the study of contagion and cascading phenomena in networks. While the model has been extensively studied it has largely resisted rigorous analysis, prior results from the literature generally pertaining to variants of the model which are tweaked so as to be amenable to standard techniques from statistical mechanics or stochastic evolutionary game theory. In Brandt et al (2012 Proc. 44th Annual ACM Symp. on Theory of Computing) provided the first rigorous analysis of the unperturbed model, for a specific set of input parameters. Here we provide a rigorous analysis of the model’s behaviour much more generally and establish some surprising forms of threshold behaviour, notably the existence of situations where an increased level of intolerance for neighbouring agents of opposite type leads almost certainly to decreased segregation.