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Sample records for calcium entry pathway

  1. Mechanism of store-operated calcium entry

    Indian Academy of Sciences (India)

    Devkanya Dutta

    2000-12-01

    Activation of receptors coupled to the phospholipase C/IP3 signalling pathway results in a rapid release of calcium from its intracellular stores, eventually leading to depletion of these stores. Calcium store depletion triggers an influx of extracellular calcium across the plasma membrane, a mechanism known as the store-operated calcium entry or capacitative calcium entry. Capacitative calcium current plays a key role in replenishing calcium stores and activating various physiological processes. Despite considerable efforts, very little is known about the molecular nature of the capacitative channel and the signalling pathway that activates it. This review summarizes our current knowledge about store operated calcium entry and suggests possible hypotheses for its mode of activation.

  2. Calcium paradox and calcium entry blockers

    NARCIS (Netherlands)

    Ruigrok, T.J.C.; Slade, A.M.; Nayler, W.G.; Meijler, F.L.

    1984-01-01

    Reperfusion of isolated hearts with calcium-containing solution after a short period of calcium-free perfusion results in irreversible cell damage (calcium paradox). This phenomenon is characterized by an excessive influx of calcium into the cells, the rapid onset of myocardial contracture, exhausti

  3. Calcium entry into guinea-pig jejunum cells after calcium stores depletion.

    Science.gov (United States)

    Pacaud, P; Bolton, T B

    1991-01-01

    1) Membrane currents were recorded under voltage-clamp from cells using patch-clamp pipettes. Cells were dialysed with potassium-free caesium solution to block any Ca-activated K-current. The pipette solution contained Indo-1 and the ratio of the emissions from this dye at 480 and 405 nm was used to estimate the free calcium concentration in the cell. 2) Carbachol applied to the cell evoked at -50 mV an initial increase in the intracellular calcium concentration (Cai) followed by a smaller sustained rise (plateau); the changes in inward cationic current (ICarb) closely followed changes in Cai. Calcium entry blockers did not affect these responses. 3) The initial peak in Cai produced by carbachol was due to calcium store release: it was present in calcium-free solution, and unchanged at +50 mV, but it was abolished by prior application of caffeine (10 mM) to the cell or by inclusion of heparin (which blocks D-myoinositol 1,4,5-trisphosphate receptors) in the pipette. 4) The sustained rise (plateau) in Cai produced by carbachol was due to the entry of calcium into the cell down its electrochemical gradient as it was affected by changing the cell membrane potential or the calcium concentration in the bathing solution. As the sustained rise in Cai produced by caffeine had similar properties it was suggested that depletion of calcium stores can evoke an increased calcium entry into the cell through some pathway. PMID:1665265

  4. Dual pathways of calcium entry in spike and plateau phases of luteinizing hormone release from chicken pituitary cells: sequential activation of receptor-operated and voltage-sensitive calcium channels by gonadotropin-releasing hormone

    International Nuclear Information System (INIS)

    It has previously been shown that, in pituitary gonadotrope cells, the initial rise in cytosolic Ca2+ induced by GnRH is due to a Ca2+ mobilization from intracellular stores. This raises the possibility that the initial transient spike phase of LH release might be fully or partially independent of extracellular Ca2+. We have therefore characterized the extracellular Ca2+ requirements, and the sensitivity to Ca2+ channel blockers, of the spike and plateau phases of secretion separately. In the absence of extracellular Ca2+ the spike and plateau phases were inhibited by 65 +/- 4% and 106 +/- 3%, respectively. Both phases exhibited a similar dependence on concentration of extracellular Ca2+. However, voltage-sensitive Ca2+ channel blockers D600 and nifedipine had a negligible effect on the spike phase, while inhibiting the plateau phase by approximately 50%. In contrast, ruthenium red, Gd3+ ions, and Co2+ ions inhibited both spike and plateau phases to a similar extent as removal of extracellular Ca2+. A fraction (35 +/- 4%) of spike phase release was resistant to removal of extracellular Ca2+. This fraction was abolished after calcium depletion of the cells by preincubation with EGTA in the presence of calcium ionophore A23187, indicating that it depends on intracellular Ca2+ stores. Neither absence of extracellular Ca2+, nor the presence of ruthenium red or Gd3+ prevented mobilization of 45Ca2+ from intracellular stores by GnRH. We conclude that mobilization of intracellular stored Ca2+ is insufficient by itself to account for full spike phase LH release

  5. Dual pathways of calcium entry in spike and plateau phases of luteinizing hormone release from chicken pituitary cells: sequential activation of receptor-operated and voltage-sensitive calcium channels by gonadotropin-releasing hormone

    Energy Technology Data Exchange (ETDEWEB)

    Davidson, J.S.; Wakefield, I.K.; King, J.A.; Mulligan, G.P.; Millar, R.P.

    1988-04-01

    It has previously been shown that, in pituitary gonadotrope cells, the initial rise in cytosolic Ca2+ induced by GnRH is due to a Ca2+ mobilization from intracellular stores. This raises the possibility that the initial transient spike phase of LH release might be fully or partially independent of extracellular Ca2+. We have therefore characterized the extracellular Ca2+ requirements, and the sensitivity to Ca2+ channel blockers, of the spike and plateau phases of secretion separately. In the absence of extracellular Ca2+ the spike and plateau phases were inhibited by 65 +/- 4% and 106 +/- 3%, respectively. Both phases exhibited a similar dependence on concentration of extracellular Ca2+. However, voltage-sensitive Ca2+ channel blockers D600 and nifedipine had a negligible effect on the spike phase, while inhibiting the plateau phase by approximately 50%. In contrast, ruthenium red, Gd3+ ions, and Co2+ ions inhibited both spike and plateau phases to a similar extent as removal of extracellular Ca2+. A fraction (35 +/- 4%) of spike phase release was resistant to removal of extracellular Ca2+. This fraction was abolished after calcium depletion of the cells by preincubation with EGTA in the presence of calcium ionophore A23187, indicating that it depends on intracellular Ca2+ stores. Neither absence of extracellular Ca2+, nor the presence of ruthenium red or Gd3+ prevented mobilization of 45Ca2+ from intracellular stores by GnRH. We conclude that mobilization of intracellular stored Ca2+ is insufficient by itself to account for full spike phase LH release.

  6. Outward potassium current oscillations in macrophage polykaryons: extracellular calcium entry and calcium-induced calcium release

    Directory of Open Access Journals (Sweden)

    Saraiva R.M.

    1997-01-01

    Full Text Available Outward current oscillations associated with transient membrane hyperpolarizations were induced in murine macrophage polykaryons by membrane depolarization in the absence of external Na+. Oscillations corresponded to a cyclic activation of Ca2+-dependent K+ currents (IKCa probably correlated with variations in intracellular Ca2+ concentration. Addition of external Na+ (8 mM immediately abolished the outward current oscillations, suggesting that the absence of the cation is necessary not only for their induction but also for their maintenance. Oscillations were completely blocked by nisoldipine. Ruthenium red and ryanodine reduced the number of outward current cycles in each episode, whereas quercetin prolonged the hyperpolarization 2- to 15-fold. Neither low molecular weight heparin nor the absence of a Na+ gradient across the membrane had any influence on oscillations. The evidence suggests that Ca2+ entry through a pathway sensitive to Ca2+ channel blockers is elicited by membrane depolarization in Na+-free medium and is essential to initiate oscillations, which are also dependent on the cyclic release of Ca2+ from intracellular Ca2+-sensitive stores; Ca2+ ATPase acts by reducing intracellular Ca2+, thus allowing slow deactivation of IKCa. Evidence is presented that neither a Na+/Ca2+ antiporter nor Ca2+ release from IP3-sensitive Ca2+ stores participate directly in the mechanism of oscillation

  7. INHIBITING MAP KINASE ACTIVITY PREVENTS CALCIUM TRANSIENTS AND MITOSIS ENTRY IN EARLY SEA URCHIN EMBRYOS

    OpenAIRE

    Philipova, Rada; Larman, Mark G.; Leckie, Calum P.; Harrison, Patrick K.; Groigno, Laurence; Whitaker, Michael

    2005-01-01

    A transient calcium increase triggers nuclear envelope breakdown (mitosis entry) in sea urchin embryos. Cdk1/cyclin B kinase activation is also known to be required for mitosis entry. More recently MAP kinase activity has also been shown to increase during mitosis. In sea urchin embryos both kinases show a similar activation profile, peaking at the time of mitosis entry.

  8. T-type calcium channel: a privileged gate for calcium entry and control of adrenal steroidogenesis

    Directory of Open Access Journals (Sweden)

    Michel Florian Rossier

    2016-05-01

    -type channels have been described yet to affect cortisol secretion or to be linked to the development of Cushing syndrome, but several evidences suggest that the function of T channels is also crucial in fasciculata cells. Putative molecular mechanisms and cellular structural organization making T channels a privileged entry for the steroidogenic calcium are also discussed.

  9. Multiple oxygen entry pathways in globin proteins revealed by intrinsic pathway identification method

    Science.gov (United States)

    Takayanagi, Masayoshi; Kurisaki, Ikuo; Nagaoka, Masataka

    2015-12-01

    Each subunit of human hemoglobin (HbA) stores an oxygen molecule (O2) in the binding site (BS) cavity near the heme group. The BS is buried in the interior of the subunit so that there is a debate over the O2 entry pathways from solvent to the BS; histidine gate or multiple pathways. To elucidate the O2 entry pathways, we executed ensemble molecular dynamics (MD) simulations of T-state tetramer HbA in high concentration O2 solvent to simulate spontaneous O2 entry from solvent into the BS. By analyzing 128 independent 8 ns MD trajectories by intrinsic pathway identification by clustering (IPIC) method, we found 141 and 425 O2 entry events into the BS of the α and β subunits, respectively. In both subunits, we found that multiple O2 entry pathways through inside cavities play a significant role for O2 entry process of HbA. The rate constants of O2 entry estimated from the MD trajectories correspond to the experimentally observed values. In addition, by analyzing monomer myoglobin, we verified that the high O2 concentration condition can reproduce the ratios of each multiple pathway in the one-tenth lower O2 concentration condition. These indicate the validity of the multiple pathways obtained in our MD simulations.

  10. Progesterone suppressed vasoconstriction in human umbilical vein via reducing calcium entry.

    Science.gov (United States)

    He, Yun; Gao, Qinqin; Han, Bing; Zhu, Xiaolin; Zhu, Di; Tao, Jianying; Chen, Jie; Xu, Zhice

    2016-04-01

    The aim of this study was to evaluate the actions of progesterone on human umbilical vein (HUV) from normal pregnancies and the possible underlying mechanisms involved. HUV rings were suspended in organ baths and exposed to progesterone followed by phenylephrine (PE) or serotonin (5-HT). Progesterone suppressed PE- or 5-HT-induced vasoconstriction in HUV rings. The inhibitory effect induced by progesterone was not influenced by nitric oxide syntheses inhibitor, prostaglandins syntheses blocker, the integrity of endothelium, selective progesterone receptor or potassium channel antagonists. Further testing showed that progesterone and nifedipine (a blocker for L-type calcium channels) produced similar inhibitory effects on PE-, 5-HT-, Bay-k8644-, KCl-induced vasoconstriction in Krebs solution as well as CaCl2-induced vasoconstriction in Ca(2+)-free Krebs solution. But the inhibitory effect of mibefradil (mibe, a blocker for L-type (CaV1.2) and T-type calcium channels (CaV3.2)) on PE-, 5-HT-induced vasoconstriction was significantly greater than progesterone or nifedipine in Krebs solution. Furthermore, progesterone did not affect the vasoconstriction caused by PE, 5-HT, or caffeine in Ca(2+)-free Krebs solution. In addition, incubation HUV with progesterone did not change CaV1.2 and progesterone receptor (PR) expressions. The results gained demonstrated that progesterone could suppress multiple agonist-induced vasoconstrictions in HUV, mainly due to a reduction of calcium entry through L-type calcium channels, not endothelium-dependent vascular relaxation pathways, potassium channels, or Ca(2+) release from intracellular stores, providing new information important to further understanding the contribution of progesterone in the regulation of the placental-fetal circulation. PMID:26875775

  11. Differential regulation of calcium signalling pathways by components of Piper methysticum (‘Awa)

    Science.gov (United States)

    Shimoda, L.M.N; Showman, A.; Baker, J.D.; Lange, I.; Koomoa, D.L.; Stokes, A.J.; Borris, R.P.; Turner, H.

    2015-01-01

    Kava is a soporific, anxiolytic and relaxant in widespread ritual and recreational use throughout the Pacific. Traditional uses of kava by indigenous Pacific Island peoples reflect a complex pharmacopeia, centered on GABA-ergic effects of the well-characterized kavalactones. However, peripheral effects of kava suggest active components other than the CNS-targeted kavalactones. We have previously shown that immunocytes exhibit calcium mobilization in response to traditionally-prepared kava extracts, and that the kavalactones do not induce these calcium responses. Here, we characterize the complex calcium-mobilizing activity of traditionally-prepared and partially HPLC-purified kava extracts, noting induction of both calcium entry and store release pathways. Kava components activate intracellular store depletion of thapsigargin-sensitive and –insensitive stores that are coupled to the calcium release activated (CRAC) current, and cause calcium entry through non-store-operated pathways. Together with the pepper-like potency reported by kava users, these studies lead us to hypothesize that kava extracts contain one or more ligands for the transient receptor potential (TRP) family of ion channels. Indeed, TRP-like conductances are observed in kava-treated cells under patch clamp. Thus TRP-mediated cellular effects may be responsible for some of the reported pharmacology of kava. PMID:25640812

  12. Modularized study of human calcium signalling pathway

    Indian Academy of Sciences (India)

    Losiana Nayak; Rajat K De

    2007-08-01

    Signalling pathways are complex biochemical networks responsible for reg ulation of numerous cellular functions. These networks function by serial and successive interactions among a large number of vital biomolecules and chemical compounds. For deciphering and analysing the underlying mechanism of such networks, a modularized study is quite helpful. Here we propose an algorithm for modularization of calcium signalling pathway of H. sapiens. The idea that ``a node whose function is dependant on maximum number of other nodes tends to be the center of a sub network” is used to divide a large signalling network into smaller sub networks. Inclusion of node(s) into sub networks(s) is dependant on the outdegree of the node(s). Here outdegree of a node refers to the number of re lations of the considered node lying outside the constructed sub network. Node(s) having more than c relations lying outside the expanding subnetwork have to be excluded from it. Here is a specified variable based on user preference, which is finally fixed during adjustments of created subnetworks, so that certain biological significance can be conferred on them.

  13. Role of AQP2 in activation of calcium entry by hypotonicity: implications in cell volume regulation.

    Science.gov (United States)

    Galizia, L; Flamenco, M P; Rivarola, V; Capurro, C; Ford, P

    2008-03-01

    We previously reported in a rat cortical collecting duct cell line (RCCD(1)) that the presence of aquaporin 2 (AQP2) in the cell membrane is critical for the rapid activation of regulatory volume decrease mechanisms (RVD) (Ford et al. Biol Cell 97: 687-697, 2005). The aim of our present work was to investigate the signaling pathway that links AQP2 to this rapid RVD activation. Since it has been previously described that hypotonic conditions induce intracellular calcium ([Ca(2+)](i)) increases in different cell types, we tested the hypothesis that AQP2 could have a role in activation of calcium entry by hypotonicity and its implication in cell volume regulation. Using a fluorescent probe technique, we studied [Ca(2+)](i) and cell volume changes in response to a hypotonic shock in WT-RCCD(1) (not expressing aquaporins) and in AQP2-RCCD(1) (transfected with AQP2) cells. We found that after a hypotonic shock only AQP2-RCCD(1) cells exhibit a substantial increase in [Ca(2+)](i). This [Ca(2+)](i) increase is strongly dependent on extracellular Ca(2+) and is partially inhibited by thapsigargin (1 muM) indicating that the rise in [Ca(2+)](i) reflects both influx from the extracellular medium and release from intracellular stores. Exposure of AQP2-RCCD(1) cells to 100 muM gadolinium reduced the increase in [Ca(2+)](i) suggesting the involvement of a mechanosensitive calcium channel. Furthermore, exposure of cells to all of the above described conditions impaired rapid RVD. We conclude that the expression of AQP2 in the cell membrane is critical to produce the increase in [Ca(2+)](i) which is necessary to activate RVD in RCCD(1) cells. PMID:18094031

  14. Tyrosine phosphorylation modulates store-operated calcium entry in cultured rat epididymal basal cells.

    Science.gov (United States)

    Zuo, Wu-Lin; Du, Jian-Yang; Huang, Jie-Hong; Li, Sheng; Zhang, Geng; Chen, Si-Liang; Ruan, Ye-Chun; Cheng, Christopher H K; Zhou, Wen-Liang

    2011-04-01

    Store-operated calcium entry (SOCE) is essential for many cellular processes. In this study, we investigated modulation of SOCE by tyrosine phosphorylation in rat epididymal basal cells. The intracellular Ca(2+) ([Ca(2+)]i) measurement showed that SOCE occurred in rat epididymal basal cells by pretreating the cells with thapsigargin (Tg), the inhibitor of sarco-endoplasmic reticulum Ca(2+)-ATPase. To identify the role of Ca(2+) channels in this response, we examined the effects of transient receptor potential canonical channel blockers 2-aminoethoxydiphenyl borate (2-APB), 1-[β-[3-(4-methoxyphenyl)pro-poxy]-4-methoxyphenethyl]-1H-imidazole hydrochloride(SKF96365), Gd(3+), and non-selective cation channel blocker Ni(2+) respectively on SOCE and found that these blockers could inhibit the Ca(2+) influx to different extent. Furthermore, we studied the regulation of SOCE by tyrosine kinase pathway. The inhibitor of tyrosine kinase genistein remarkably suppressed the SOCE response, whereas sodium orthovanadate, the inhibitor of tyrosine phosphatase, greatly enhanced it. The results suggest that tyrosine kinase pathway plays a significant role in the initiation of SOCE and positively modulates SOCE in epididymal basal cells. PMID:20857412

  15. Two chromogranin a-derived peptides induce calcium entry in human neutrophils by calmodulin-regulated calcium independent phospholipase A2.

    Directory of Open Access Journals (Sweden)

    Dan Zhang

    Full Text Available BACKGROUND: Antimicrobial peptides derived from the natural processing of chromogranin A (CgA are co-secreted with catecholamines upon stimulation of chromaffin cells. Since PMNs play a central role in innate immunity, we examine responses by PMNs following stimulation by two antimicrobial CgA-derived peptides. METHODOLOGY/PRINCIPAL FINDINGS: PMNs were treated with different concentrations of CgA-derived peptides in presence of several drugs. Calcium mobilization was observed by using flow cytometry and calcium imaging experiments. Immunocytochemistry and confocal microscopy have shown the intracellular localization of the peptides. The calmodulin-binding and iPLA2 activating properties of the peptides were shown by Surface Plasmon Resonance and iPLA2 activity assays. Finally, a proteomic analysis of the material released after PMNs treatment with CgA-derived peptides was performed by using HPLC and Nano-LC MS-MS. By using flow cytometry we first observed that after 15 s, in presence of extracellular calcium, Chromofungin (CHR or Catestatin (CAT induce a concentration-dependent transient increase of intracellular calcium. In contrast, in absence of extra cellular calcium the peptides are unable to induce calcium depletion from the stores after 10 minutes exposure. Treatment with 2-APB (2-aminoethoxydiphenyl borate, a store operated channels (SOCs blocker, inhibits completely the calcium entry, as shown by calcium imaging. We also showed that they activate iPLA2 as the two CaM-binding factors (W7 and CMZ and that the two sequences can be aligned with the two CaM-binding domains reported for iPLA2. We finally analyzed by HPLC and Nano-LC MS-MS the material released by PMNs following stimulation by CHR and CAT. We characterized several factors important for inflammation and innate immunity. CONCLUSIONS/SIGNIFICANCE: For the first time, we demonstrate that CHR and CAT, penetrate into PMNs, inducing extracellular calcium entry by a CaM-regulated i

  16. Molecular modulators of store-operated calcium entry.

    Science.gov (United States)

    Lopez, Jose J; Albarran, Letizia; Gómez, Luis J; Smani, Tarik; Salido, Gines M; Rosado, Juan A

    2016-08-01

    Three decades ago, store-operated Ca(2+) entry (SOCE) was identified as a unique mechanism for Ca(2+) entry through plasma membrane (PM) Ca(2+)-permeable channels modulated by the intracellular Ca(2+) stores, mainly the endoplasmic reticulum (ER). Extensive analysis of the communication between the ER and the PM leads to the identification of the protein STIM1 as the ER-Ca(2+) sensor that gates the Ca(2+) channels in the PM. Further analysis on the biophysical, electrophysiological and biochemical properties of STIM1-dependent Ca(2+) channels has revealed the presence of a highly Ca(2+)-selective channel termed Ca(2+) release-activated Ca(2+) channel (CRAC), consisting of Orai1 subunits, and non-selective cation channels named store-operated channels (SOC), including both Orai1 and TRPC channel subunits. Since the identification of the key elements of CRAC and SOC channels a number of intracellular modulators have been reported to play essential roles in the stabilization of STIM-Orai interactions, collaboration with STIM1 conformational changes or mediating slow Ca(2+)-dependent inactivation. Here, we review our current understanding of some of the key modulators of STIM1-Orai1 interaction, including the proteins CRACR2A, STIMATE, SARAF, septins, golli and ORMDL3. PMID:27130253

  17. Second Messenger-Operated Calcium Entry Through TRPC6.

    Science.gov (United States)

    Bouron, Alexandre; Chauvet, Sylvain; Dryer, Stuart; Rosado, Juan A

    2016-01-01

    Canonical transient receptor potential 6 (TRPC6) proteins assemble into heteromultimeric structures forming non-selective cation channels. In addition, many TRPC6-interacting proteins have been identified like some enzymes, channels, pumps, cytoskeleton-associated proteins, immunophilins, or cholesterol-binding proteins, indicating that TRPC6 are engaged into macromolecular complexes. Depending on the cell type and the experimental conditions used, TRPC6 activity has been reported to be controlled by diverse modalities. For instance, the second messenger diacylglycerol, store-depletion, the plant extract hyperforin or H2O2 have all been shown to trigger the opening of TRPC6 channels. A well-characterized consequence of TRPC6 activation is the elevation of the cytosolic concentration of Ca(2+). This latter response can reflect the entry of Ca(2+) through open TRPC6 channels but it can also be due to the Na(+)/Ca(2+) exchanger (operating in its reverse mode) or voltage-gated Ca(2+) channels (recruited in response to a TRPC6-mediated depolarization). Although TRPC6 controls a diverse array of biological functions in many tissues and cell types, its pathophysiological functions are far from being fully understood. This chapter covers some key features of TRPC6, with a special emphasis on their biological significance in kidney and blood cells. PMID:27161231

  18. Calcium influx pathways in rat pancreatic ducts

    DEFF Research Database (Denmark)

    Hug, M J; Pahl, C; Novak, I

    1996-01-01

    A number of agonists increase intracellular Ca2+ activity, [Ca2+]i, in pancreatic ducts, but the influx/efflux pathways and intracellular Ca2+ stores in this epithelium are unknown. The aim of the present study was to characterise the Ca2+ influx pathways, especially their pH sensitivity, in nati...

  19. On the molecular basis and regulation of cellular capacitative calcium entry: Roles for Trp proteins

    OpenAIRE

    Birnbaumer, Lutz; Zhu, Xi; Jiang, Meisheng; Boulay, Guylain; Peyton, Michael; Vannier, Brigitte; Brown, Darren; Platano, Daniela; Sadeghi, Hamid; Stefani, Enrico; Birnbaumer, Mariel

    1996-01-01

    During the last 2 years, our laboratory has worked on the elucidation of the molecular basis of capacitative calcium entry (CCE) into cells. Specifically, we tested the hypothesis that CCE channels are formed of subunits encoded in genes related to the Drosophila trp gene. The first step in this pursuit was to search for mammalian trp genes. We found not one but six mammalian genes and cloned several of their cDNAs, some in their full length. As assayed in mammalia...

  20. Chlorpromazine inhibits store-operated calcium entry and subsequent noradrenaline secretion in PC12 cells

    OpenAIRE

    Choi, Se-Young; Kim, Yong-Hyun; Lee, Yong-kyu; Kim, Kyong-Tai

    2001-01-01

    The effect of chlorpromazine on the store-operated Ca2+ entry activated via the phospholipase C signalling pathway was investigated in PC12 cells.Chlorpromazine inhibited the sustained increase after the initial peak in the intracellular Ca2+ concentration produced by bradykinin while having no effect on the initial transient response. The inhibition was lowered by the removal of extracellular free Ca2+. However, chlorpromazine did not inhibit bradykinin-induced inositol 1,4,5-trisphosphate p...

  1. Endocytic Pathways Involved in Filovirus Entry: Advances, Implications and Future Directions

    Directory of Open Access Journals (Sweden)

    Suchita Bhattacharyya

    2012-12-01

    Full Text Available Detailed knowledge of the host-virus interactions that accompany filovirus entry into cells is expected to identify determinants of viral virulence and host range, and to yield targets for the development of antiviral therapeutics. While it is generally agreed that filovirus entry into the host cytoplasm requires viral internalization into acidic endosomal compartments and proteolytic cleavage of the envelope glycoprotein by endo/lysosomal cysteine proteases, our understanding of the specific endocytic pathways co-opted by filoviruses remains limited. This review addresses the current knowledge on cellular endocytic pathways implicated in filovirus entry, highlights the consensus as well as controversies, and discusses important remaining questions.

  2. The Inositol Trisphosphate/Calcium Signaling Pathway in Health and Disease.

    Science.gov (United States)

    Berridge, Michael J

    2016-10-01

    Many cellular functions are regulated by calcium (Ca(2+)) signals that are generated by different signaling pathways. One of these is the inositol 1,4,5-trisphosphate/calcium (InsP3/Ca(2+)) signaling pathway that operates through either primary or modulatory mechanisms. In its primary role, it generates the Ca(2+) that acts directly to control processes such as metabolism, secretion, fertilization, proliferation, and smooth muscle contraction. Its modulatory role occurs in excitable cells where it modulates the primary Ca(2+) signal generated by the entry of Ca(2+) through voltage-operated channels that releases Ca(2+) from ryanodine receptors (RYRs) on the internal stores. In carrying out this modulatory role, the InsP3/Ca(2+) signaling pathway induces subtle changes in the generation and function of the voltage-dependent primary Ca(2+) signal. Changes in the nature of both the primary and modulatory roles of InsP3/Ca(2+) signaling are a contributory factor responsible for the onset of a large number human diseases. PMID:27512009

  3. The cell surface expressed nucleolin is a glycoprotein that triggers calcium entry into mammalian cells

    International Nuclear Information System (INIS)

    Nucleolin is an ubiquitous nucleolar phosphoprotein involved in fundamental aspects of transcription regulation, cell proliferation and growth. It has also been described as a shuttling molecule between nucleus, cytosol and the cell surface. Several studies have demonstrated that surface nucleolin serves as a receptor for various extracellular ligands implicated in cell proliferation, differentiation, adhesion, mitogenesis and angiogenesis. Previously, we reported that nucleolin in the extranuclear cell compartment is a glycoprotein containing N- and O-glycans. In the present study, we show that glycosylation is an essential requirement for surface nucleolin expression, since it is prevented when cells are cultured in the presence of tunicamycin, an inhibitor of N-glycosylation. Accordingly, surface but not nuclear nucleolin is radioactively labeled upon metabolic labeling of cells with [3H]glucosamine. Besides its well-demonstrated role in the internalization of specific ligands, here we show that ligand binding to surface nucleolin could also induce Ca2+ entry into cells. Indeed, by flow cytometry, microscopy and patch-clamp experiments, we show that the HB-19 pseudopeptide, which binds specifically surface nucleolin, triggers rapid and intense membrane Ca2+ fluxes in various types of cells. The use of several drugs then indicated that Store-Operated Ca2+ Entry (SOCE)-like channels are involved in the generation of these fluxes. Taken together, our findings suggest that binding of an extracellular ligand to surface nucleolin could be involved in the activation of signaling pathways by promoting Ca2+ entry into cells

  4. How antibodies alter the cell entry pathway of dengue virus particles in macrophages

    Science.gov (United States)

    Ayala-Nunez, Nilda V.; Hoornweg, Tabitha E.; van de Pol, Denise P.I.; Sjollema, Klaas A.; Flipse, Jacky; van der Schaar, Hilde M.; Smit, Jolanda M.

    2016-01-01

    Antibody-dependent enhancement of dengue virus (DENV) infection plays an important role in the exacerbation of DENV-induced disease. To understand how antibodies influence the fate of DENV particles, we explored the cell entry pathway of DENV in the absence and presence of antibodies in macrophage-like P388D1 cells. Recent studies unraveled that both mature and immature DENV particles contribute to ADE, hence, both particles were studied. We observed that antibody-opsonized DENV enters P388D1 cells through a different pathway than non-opsonized DENV. Antibody-mediated DENV entry was dependent on FcγRs, pH, Eps15, dynamin, actin, PI3K, Rab5, and Rab7. In the absence of antibodies, DENV cell entry was FcγR, PI3K, and Rab5-independent. Live-cell imaging of fluorescently-labeled particles revealed that actin-mediated membrane protrusions facilitate virus uptake. In fact, actin protrusions were found to actively search and capture antibody-bound virus particles distantly located from the cell body, a phenomenon that is not observed in the absence of antibodies. Overall, similar results were seen for antibody-opsonized standard and antibody-bound immature DENV preparations, indicating that the maturation status of the virus does not control the entry pathway. Collectively, our findings suggest that antibodies alter the cell entry pathway of DENV and trigger a novel mechanism of initial virus-cell contact. PMID:27385443

  5. Defective Store-Operated Calcium Entry Causes Partial Nephrogenic Diabetes Insipidus.

    Science.gov (United States)

    Mamenko, Mykola; Dhande, Isha; Tomilin, Viktor; Zaika, Oleg; Boukelmoune, Nabila; Zhu, Yaming; Gonzalez-Garay, Manuel L; Pochynyuk, Oleh; Doris, Peter A

    2016-07-01

    Store-operated calcium entry (SOCE) is the mechanism by which extracellular signals elicit prolonged intracellular calcium elevation to drive changes in fundamental cellular processes. Here, we investigated the role of SOCE in the regulation of renal water reabsorption, using the inbred rat strain SHR-A3 as an animal model with disrupted SOCE. We found that SHR-A3, but not SHR-B2, have a novel truncating mutation in the gene encoding stromal interaction molecule 1 (STIM1), the endoplasmic reticulum calcium (Ca(2+)) sensor that triggers SOCE. Balance studies revealed increased urine volume, hypertonic plasma, polydipsia, and impaired urinary concentrating ability accompanied by elevated circulating arginine vasopressin (AVP) levels in SHR-A3 compared with SHR-B2. Isolated, split-open collecting ducts (CD) from SHR-A3 displayed decreased basal intracellular Ca(2+) levels and a major defect in SOCE. Consequently, AVP failed to induce the sustained intracellular Ca(2+) mobilization that requires SOCE in CD cells from SHR-A3. This effect decreased the abundance of aquaporin 2 and enhanced its intracellular retention, suggesting impaired sensitivity of the CD to AVP in SHR-A3. Stim1 knockdown in cultured mpkCCDc14 cells reduced SOCE and basal intracellular Ca(2+) levels and prevented AVP-induced translocation of aquaporin 2, further suggesting the effects in SHR-A3 result from the expression of truncated STIM1. Overall, these results identify a novel mechanism of nephrogenic diabetes insipidus and uncover a role of SOCE in renal water handling. PMID:26574044

  6. Binding of Adenovirus Capsid to Dipalmitoyl Phosphatidylcholine Provides a Novel Pathway for Virus Entry

    OpenAIRE

    Balakireva, Larissa; Schoehn, Guy; Thouvenin, Eric; Chroboczek, Jadwiga

    2003-01-01

    Adenovirus (Ad) is an airborne, nonenveloped virus infecting respiratory epithelium. To study the mechanism of Ad entry, we used alveolar adenocarcinoma A549 cells, which have retained the ability of alveolar epithelial type II cells to synthesize the major component of pulmonary surfactant, disaturated phosphatidylcholine. Stimulation of phosphatidylcholine secretion by calcium ionophore or phorbol ester augmented the susceptibility of these cells to Ad. Both Ad infection and recombinant-Ad-...

  7. Pathways for entry of livestock arboviruses into Great Britain: assessing the strength of evidence.

    Science.gov (United States)

    Gale, P; Kelly, L; Snary, E L

    2015-04-01

    The emergence of bluetongue virus and Schmallenberg virus in Great Britain (GB) during the last decade has highlighted the need for understanding the relative importance of the various pathways of the entry of livestock arboviruses so as to help focus surveillance and mitigation. This study summarizes what is known for the main routes of entry and assesses the strength of the current evidence for and against. Entry through infected arthropod vectors is considered at the level of each life cycle stage for tick-, biting midge- and mosquito-borne viruses, and while there is evidence that this could happen through most tick and mosquito stages, strong evidence that only exists for entry through adult midges. There is also strong evidence that entry through immature midge stages could not happen. The weight of supporting evidence is strongest for importation of viraemic livestock including horses. While there is some indication of a common pathway for midge-borne viruses from sub-Saharan Africa to GB via Continental Europe, other factors such as maternal transmission in dogs and sheep need to be considered in the light of recent findings. PMID:25580655

  8. Inhibition of Store-Operated Calcium Entry Protects Endothelial Progenitor Cells from H2O2-Induced Apoptosis.

    Science.gov (United States)

    Wang, Yan-Wei; Zhang, Ji-Hang; Yu, Yang; Yu, Jie; Huang, Lan

    2016-07-01

    Store-operated calcium entry (SOCE), a major mode of extracellular calcium entry, plays roles in a variety of cell activities. Accumulating evidence indicates that the intracellular calcium ion concentration and calcium signaling are critical for the responses induced by oxidative stress. The present study was designed to investigate the potential effect of SOCE inhibition on H2O2-induced apoptosis in endothelial progenitor cells (EPCs), which are the predominant cells involved in endothelial repair. The results showed that H2O2-induced EPC apoptosis was reversed by SOCE inhibition induced either using the SOCE antagonist ML-9 or via silencing of stromal interaction molecule 1 (STIM1), a component of SOCE. Furthermore, SOCE inhibition repressed the increases in intracellular reactive oxygen species (ROS) levels and endoplasmic reticulum (ER) stress and ameliorated the mitochondrial dysfunction caused by H2O2. Our findings provide evidence that SOCE inhibition exerts a protective effect on EPCs in response to oxidative stress induced by H2O2 and may serve as a potential therapeutic strategy against vascular endothelial injury. PMID:27169819

  9. Calcium sensing receptor suppresses human pancreatic tumorigenesis through a novel NCX1/Ca(2+)/β-catenin signaling pathway.

    Science.gov (United States)

    Tang, Bo; Chow, Jimmy Y C; Dong, Tobias Xiao; Yang, Shi-Ming; Lu, De-Sheng; Carethers, John M; Dong, Hui

    2016-07-10

    The calcium sensing receptor (CaSR) is functionally expressed in normal human pancreases, but its pathological role in pancreatic tumorigenesis is currently unknown. We sought to investigate the role of CaSR in pancreatic cancer (PC) and the underlying molecular mechanisms. We revealed that the expression of CaSR was consistently downregulated in the primary cancer tissues from PC patients, which was correlated with tumor size, differentiation and poor survival of the patients. CaSR activation markedly suppressed pancreatic tumorigenesis in vitro and in vivo likely through the Ca(2+) entry mode of Na(+)/Ca(2+) exchanger 1 (NCX1) to induce Ca(2+) entry into PC cells. Moreover, NCX1-mediated Ca(2+) entry resulted in Ca(2+)-dependent inhibition of β-catenin signaling in PC cells, eventually leading to the inhibition of pancreatic tumorigenesis. Collectively, we demonstrate for the first time that CaSR exerts a suppressive function in pancreatic tumorigenesis through a novel NCX1/Ca(2+)/β-catenin signaling pathway. Targeting this specific signaling pathway could be a potential therapeutic strategy for PC. PMID:27108064

  10. SARS coronavirus entry into host cells through a novel clathrin- and caveolae-independent endocytic pathway

    Institute of Scientific and Technical Information of China (English)

    Hongliang Wang; Peng Yang; Kangtai Liu; Feng Guo; Yanli Zhang; Gongyi Zhang; Chengyu Jiang

    2008-01-01

    While severe acute respiratory syndrome coronavirus (SARS-CoV)fwas initially thought to enter cells through direct fusion with the plasma membrane, more recent evidence suggests that virus entry may also involve endocytosis. We have found that SARS-CoV enters cells via pH- and receptor-dependent endocytosis. Treatment of cells with either SARS-CoV spike protein or spike-bearing pseudoviruses resulted in the translocation of angiotensin-converting enzyme 2 (ACE2), the functional receptor of SARS-CoV, from the cell surface to endosomes. In addition, the spike-bearing pseudoviruses and early endosome antigen 1 were found to colocalize in endosomes. Further analyses using specific endocytic pathway inhibitors and dominant-negative Eps15 as well as caveolin-1 colocalization study suggested that virus entry was mediated by a clathrin- and caveolae-independent mechanism. Moreover, cholesterol- and sphingolipid-rich lipid raft microdomains in the plasma membrane, which have been shown to act as platforms for many physiological signaling pathways, were shown to be involved in virus entry. Endocytic entry of SARS-CoV may expand the cellular range of SARS-CoV infection, and our findings here contribute to the understanding of SARS-CoV pathogenesis, providing new information for anti-viral drug research.

  11. PDGF receptor-α does not promote HCMV entry into epithelial and endothelial cells but increased quantities stimulate entry by an abnormal pathway.

    Directory of Open Access Journals (Sweden)

    Adam L Vanarsdall

    2012-09-01

    Full Text Available Epidermal growth factor receptor (EGFR and platelet-derived growth factor receptor-α (PDGFRα were reported to mediate entry of HCMV, including HCMV lab strain AD169. AD169 cannot assemble gH/gL/UL128-131, a glycoprotein complex that is essential for HCMV entry into biologically important epithelial cells, endothelial cells, and monocyte-macrophages. Given this, it appeared incongruous that EGFR and PDGFRα play widespread roles in HCMV entry. Thus, we investigated whether PDGFRα and EGFR could promote entry of wild type HCMV strain TR. EGFR did not promote HCMV entry into any cell type. PDGFRα-transduction of epithelial and endothelial cells and several non-permissive cells markedly enhanced HCMV TR entry and surprisingly, promoted entry of HCMV mutants lacking gH/gL/UL128-131 into epithelial and endothelial cells. Entry of HCMV was not blocked by a panel of PDGFRα antibodies or the PDGFR ligand in fibroblasts, epithelial, or endothelial cells or by shRNA silencing of PDGFRα in epithelial cells. Moreover, HCMV glycoprotein induced cell-cell fusion was not increased when PDGFRα was expressed in cells. Together these results suggested that HCMV does not interact directly with PDGFRα. Instead, the enhanced entry produced by PDGFRα resulted from a novel entry pathway involving clathrin-independent, dynamin-dependent endocytosis of HCMV followed by low pH-independent fusion. When PDGFRα was expressed in cells, an HCMV lab strain escaped endosomes and tegument proteins reached the nucleus, but without PDGFRα virions were degraded. By contrast, wild type HCMV uses another pathway to enter epithelial cells involving macropinocytosis and low pH-dependent fusion, a pathway that lab strains (lacking gH/gL/UL128-131 cannot follow. Thus, PDGFRα does not act as a receptor for HCMV but increased PDGFRα alters cells, facilitating virus entry by an abnormal pathway. Given that PDGFRα increased infection of some cells to 90%, PDGFRα may be very

  12. Externalizing Symptoms among Children of Alcoholic Parents: Entry Points for an Antisocial Pathway to Alcoholism

    OpenAIRE

    Hussong, A.M.; Wirth, R. J.; Edwards, M. C.; Curran, P. J.; Chassin, L.A.; Zucker, R.A.

    2007-01-01

    We examined heterogeneity in risk for externalizing symptoms in children of alcoholic parents as it may inform the search for entry points into an antisocial pathway to alcoholism. Specifically, we tested whether the number of alcoholic parents in a family, the comorbid subtype of parent alcoholism, and the gender of the child predicted trajectories of externalizing symptoms over the early life course as assessed in high-risk samples of children of alcoholic parents and matched controls. Thro...

  13. Lymphocytic choriomeningitis virus uses a novel endocytic pathway for infectious entry via late endosomes

    International Nuclear Information System (INIS)

    The endocytic entry of lymphocytic choriomeningitis virus (LCMV) into host cells was compared to the entry of viruses known to exploit clathrin or caveolae/raft-dependent pathways. Pharmacological inhibitors, expression of pathway-specific dominant-negative constructs, and siRNA silencing of clathrin together with electron and light microscopy provided evidence that although a minority population followed a classical clathrin-mediated mechanism of entry, the majority of these enveloped RNA viruses used a novel endocytic route to late endosomes. The pathway was clathrin, dynamin-2, actin, Arf6, flotillin-1, caveolae, and lipid raft independent but required membrane cholesterol. Unaffected by perturbation of Rab5 or Rab7 and apparently without passing through Rab5/EEA1-positive early endosomes, the viruses reached late endosomes and underwent acid-induced penetration. This membrane trafficking route between the plasma membrane and late endosomes may function in the turnover of a select group of surface glycoproteins such as the dystroglycan complex, which serves as the receptor of LCMV

  14. Genome-wide association study knowledge-driven pathway analysis of alcohol dependence implicates the calcium signaling pathway

    Institute of Scientific and Technical Information of China (English)

    Li Danni; Li Jinming; Guo Yanfang

    2014-01-01

    Background Alcohol dependence (AD) is a serious and common public health problem.The identification of genes that contribute to the AD variation will improve our understanding of the genetic mechanism underlying this complex disease.Previous genome-wide association studies (GWAS) and candidate gene genetic association studies identified individual genes as candidates for alcohol phenotypes,but efforts to generate an integrated view of accumulative genetic variants and pathways under alcohol drinking are lacking.Methods We applied enrichment gene set analysis to existing genetic association results to identify pertinent pathways to AD in this study.A total of 1 438 SNPs (P <1.0×10-3) associated to alcohol drinking related traits have been collected from 31 studies (10 candidate gene association studies,19 GWAS of SNPs,and 2 GWAS of copy number variants).Results Among all of the KEGG pathways,the calcium signaling pathway (hsa04020) showed the most significant enrichment of associations (21 genes) to alcohol consumption phenotypes (P=5.4×10-5).Furthermore,the calcium signaling pathway is the only pathway that turned out to be significant after multiple test adjustments,achieving Bonferroni P value of 0.8×10-3 and FDR value of 0.6×10-2,respectively.Interestingly,the calcium signaling pathway was previously found to be essential to regulate brain function,and genes in this pathway link to a depressive effect of alcohol consumption on the body.Conclusions Our findings,together with previous biological evidence,suggest the importance of gene polymorphisms of calcium signaling pathway to AD susceptibility.Still,further investigations are warranted to uncover the role of this pathway in AD and related traits.

  15. The Ebola virus glycoprotein mediates entry via a non-classical dynamin-dependent macropinocytic pathway

    International Nuclear Information System (INIS)

    Ebola virus (EBOV) has been reported to enter cultured cell lines via a dynamin-2-independent macropinocytic pathway or clathrin-mediated endocytosis. The route(s) of productive EBOV internalization into physiologically relevant cell types remain unexplored, and viral-host requirements for this process are incompletely understood. Here, we use electron microscopy and complementary chemical and genetic approaches to demonstrate that the viral glycoprotein, GP, induces macropinocytic uptake of viral particles into cells. GP's highly-glycosylated mucin domain is dispensable for virus-induced macropinocytosis, arguing that interactions between other sequences in GP and the host cell surface are responsible. Unexpectedly, we also found a requirement for the large GTPase dynamin-2, which is proposed to be dispensable for several types of macropinocytosis. Our results provide evidence that EBOV uses an atypical dynamin-dependent macropinocytosis-like entry pathway to enter Vero cells, adherent human peripheral blood-derived monocytes, and a mouse dendritic cell line.

  16. Dihydropyridines as inhibitors of capacitative calcium entry in leukemic HL-60 cells

    Science.gov (United States)

    Harper, Jacquie L.; Camerini-Otero, Carol S.; Li, An-Hu; Kim, Soon-Ai; Jacobson, Kenneth A.; Daly, John W.

    2016-01-01

    A series of 1,4-dihydropyridines (DHPs) were investigated as inhibitors of capacitative calcium influx through store-operated calcium (SOC) channels. Such channels activate after ATP-elicited release of inositol trisphosphate (IP3)-sensitive calcium stores in leukemia HL-60 cells. The most potent DHPs were those containing a 4-phenyl group with an electron-withdrawing substituent, such as m- or p-nitro- or m-trifluoromethyl (IC50 values: 3–6 μM). Benzyl esters, corresponding to the usual ethyl/methyl esters of the DHPs developed as L-type calcium channel blockers, retained potency at SOC channels, as did N-substituted DHPs. N-Methylation reduced by orders of magnitude the potency at L-type channels resulting in DHPs nearly equipotent at SOC and L-type channels. DHPs with N-ethyl, N-allyl, and N-propargyl groups also had similar potencies at SOC and L-type channels. Replacement of the usual 6-methyl group of DHPs with larger groups, such as cyclobutyl or phenyl, eliminated activity at the SOC channels; such DHPs instead elicited formation of inositol phosphates and release of IP3-sensitive calcium stores. Other DHPs also caused a release of calcium stores, but usually at significantly higher concentrations than those required for the inhibition of capacitative calcium influx. Certain DHPs appeared to cause an incomplete blockade of SOC channel-dependent elevations of calcium, suggesting the presence of more than one class of such channels in HL-60 cells. N-Methylnitrendipine (IC50 2.6 μM, MRS 1844) and N-propargylnifrendipine (IC50 1.7 μM, MRS 1845) represent possible lead compounds for the development of selective SOC channel inhibitors. PMID:12527326

  17. Plasma membrane calcium ATPase proteins as novel regulators of signal transduction pathways

    Institute of Scientific and Technical Information of China (English)

    Mary; Louisa; Holton; Michael; Emerson; Ludwig; Neyses; Angel; L; Armesilla

    2010-01-01

    Emerging evidence suggests that plasma membrane calcium ATPases (PMCAs) play a key role as regulators of calcium-triggered signal transduction pathways via interaction with partner proteins. PMCAs regulate these pathways by targeting specific proteins to cellular sub-domains where the levels of intracellular freecalcium are kept low by the calcium ejection properties of PMCAs. According to this model, PMCAs have been shown to interact functionally with the calcium-sensitive proteins neuronal nitric oxide synthase, calmodulindependent serine protein kinase, calcineurin and endothelial nitric oxidase synthase. Transgenic animals with altered expression of PMCAs are being used to evaluate the physiological significance of these interactions. To date, PMCA interactions with calcium-dependent partner proteins have been demonstrated to play a crucial role in the pathophysiology of the cardiovascular system via regulation of the nitric oxide and calcineurin/nuclear factor of activated T cells pathways. This new evidence suggests that PMCAs play a more sophisticated role than the mere ejection of calcium from the cells, by acting as modulators of signaling transduction pathways.

  18. Mycoparasitism of arbuscular mycorrhizal fungi: a pathway for the entry of saprotrophic fungi into roots.

    Science.gov (United States)

    De Jaeger, Nathalie; Declerck, Stéphane; de la Providencia, Ivan E

    2010-08-01

    Within the rhizosphere, arbuscular mycorrhizal (AM) fungi interact with a cohort of microorganisms, among which is the biological control agent, Trichoderma spp. This fungus parasitizes a wide range of phytopathogenic fungi, a phenomenon also reported in the extraradical mycelium (ERM) of AM fungi. Here, we question whether the mycoparasitism of the ERM could be extended to the intraradical mycelium (IRM), thus representing a pathway for the entry of Trichoderma harzianum within the root. Microcosm experiments allowing interactions between Glomus sp. MUCL 41833 placed in a clade that contains the recently described species Glomus irregulare and T. harzianum were set up under in vitro autotrophic culture conditions using potato as a host. A microscope camera-imaging system, coupled with succinate dehydrogenase staining, was used to assess the mycoparasitism in the ERM and IRM. Trichoderma harzianum colonized the ERM of the AM fungus and spread into the IRM, before exiting into the root cells. Intrahyphal growth of T. harzianum caused protoplasm degradation, decreasing the ERM and IRM viability. ERM of the AM fungus represented a pathway for the entry of T. harzianum into the roots of potato. It further sets off the debate on the susceptibility of the AM fungi of being infected by microorganisms from the rhizosphere. PMID:20533946

  19. Relationship between calcium entry and ACh release in K+ -stimulated rat brain synaptosomes

    International Nuclear Information System (INIS)

    This paper examines the pattern of Ca++ entry-dependent ACh release in relation to the kinetics of Ca++ entry, and its inactivation in rat brain synaptosomes exposed to 50 mM K0+ for short and prolonged durations. Intrasynaptosomal ACh was radiolabeled from tritium-choline in the presence of 20 um Paraoxon to inhibit the acetylcholinesterase activity. The release of tritium-ACh was studied in superfused synaptosomal beds formed on glass microfiber filters and by rapid filtration. The intermittent stimulation of superfused synaptosomal beds by 3-min pulses of 50 mM K+ evoked decremental output of tritium-ACh which reached nearly undetectable levels after the fifth stimulus

  20. Different effects of R 56865 and calcium entry blockers on K+- and noradrenaline-induced contractions and45Ca uptake in rat aorta

    NARCIS (Netherlands)

    Koch, P.; Wilhelm, D.; Wermelskirchen, D.; Nebel, U.; Wilffert, B.; Peters, Thies

    1988-01-01

    The effects of R 56865, nifedipine, verapamil, diltiazem and flunarizine on K+- and NA-induced contractions and K+-induced45Ca uptake were compared in the isolated rat aorta. The calcium entry blockers concentration dependently inhibited the K+-induced contraction and45Ca uptake over the same dose-r

  1. Different sensitivities for four calcium entry blockers of serotonin-, but not K+-induced contractions of isolated jugular vein and aorta of the rat

    NARCIS (Netherlands)

    Gouw, M.A.M.; Wilffert, B.; Van Zwieten, P.A.

    1989-01-01

    We investigated the inhibitory effect of the calcium entry blockers (CEBs) nifedipine, diltiazem, flunarizine and gallopamil on K+- and serotonin (5-HT)-induced contractions of the rat jugular vein and aorta in vitro. In both tissues all four CEBs inhibited K+-induced contractions concentration-depe

  2. Deciphering the plasma membrane hallmarks of apoptotic cells: Phosphatidylserine transverse redistribution and calcium entry

    Directory of Open Access Journals (Sweden)

    Martínez M Carmen

    2001-10-01

    Full Text Available Abstract Background During apoptosis, Ca2+-dependent events participate in the regulation of intracellular and morphological changes including phosphatidylserine exposure in the exoplasmic leaflet of the cell plasma membrane. The occurrence of phosphatidylserine at the surface of specialized cells, such as platelets, is also essential for the assembly of the enzyme complexes of the blood coagulation cascade, as demonstrated by hemorrhages in Scott syndrome, an extremely rare genetic deficiency of phosphatidylserine externalization, without other apparent pathophysiologic consequences. We have recently reported a reduced capacitative Ca2+ entry in Scott cells which may be part of the Scott phenotype. Results Taking advantage of these mutant lymphoblastoid B cells, we have studied the relationship between this mode of Ca2+ entry and phosphatidylserine redistribution during apoptosis. Ca2+ ionophore induced apoptosis in Scott but not in control cells. However, inhibition of store-operated Ca2+ channels led to caspase-independent DNA fragmentation and decrease of mitochondrial membrane potential in both control and Scott cells. Inhibition of cytochrome P450 also reduced capacitative Ca2+ entry and induced apoptosis at comparable extents in control and Scott cells. During the apoptotic process, both control and more markedly Scott cells externalized phosphatidylserine, but in the latter, this membrane feature was however dissociated from several other intracellular changes. Conclusions The present results suggest that different mechanisms account for phosphatidylserine transmembrane migration in cells undergoing stimulation and programmed death. These observations testify to the plasticity of the plasma membrane remodeling process, allowing normal apoptosis even when less fundamental functions are defective.

  3. Actin filaments as the fast pathways for calcium ions involved in auditory processes

    Indian Academy of Sciences (India)

    Miljko V Sataric; Dalibor L Sekulic; Bogdan M Sataric

    2015-09-01

    We investigated the polyelectrolyte properties of actin filaments which are in interaction with myosin motors, basic participants in mechano-electrical transduction in the stereocilia of the inner ear. Here, we elaborated a model in which actin filaments play the role of guides or pathways for localized flow of calcium ions. It is well recognized that calcium ions are implicated in tuning of actin-myosin cross-bridge interaction, which controls the mechanical property of hair bundle. Actin filaments enable much more efficient delivery of calcium ions and faster mechanism for their distribution within the stereocilia. With this model we were able to semiquantitatively explain experimental evidences regarding the way of how calcium ions tune the mechanosensitivity of hair cells.

  4. Effect of dendroaspis natriuretic peptide (DNP) on L-type calcium channel current and its pathway.

    Science.gov (United States)

    Zhang, Shu-Ying; Cai, Zheng-Xu; Li, Ping; Cai, Chun-Yu; Qu, Cheng-Long; Guo, Hui-Shu

    2010-09-24

    Dendroaspis natriuretic peptide (DNP), a newly-described natriuretic peptide, relaxes gastrointestinal smooth muscle. L-type calcium channel currents play an important role in regulating smooth muscle contraction. The effect of DNP on L-type calcium channel currents in gastrointestinal tract is still unclear. This study was designed to investigate the effect of DNP on barium current (I(Ba)) through the L-type calcium channel in gastric antral myocytes of guinea pigs and cGMP-pathway mechanism. The whole-cell patch-clamp technique was used to record L-type calcium channel currents. The content of cGMP in guinea pig gastric antral smooth muscle and perfusion solution was measured using radioimmunoassay. DNP markedly enhanced cGMP levels in gastric antral smooth muscle tissue and in perfusion medium. DNP concentration-dependently inhibited I(Ba) in freshly isolated guinea pig gastric antral circular smooth muscle cells (SMCs) of guinea pigs. DNP-induced inhibition of I(Ba) was partially blocked by LY83583, an inhibitor of guanylate cyclase. KT5823, a cGMP-dependent protein kinase (PKG) inhibitor, almost completely blocked DNP-induced inhibition of I(Ba). However, DNP-induced inhibition of I(Ba) was potentiated by zaprinast, an inhibitor of cGMP-sensitive phosphodiesterase. Taken together, DNP inhibits L-type calcium channel currents via pGC-cGMP-PKG-dependent signal pathway in gastric antral myocytes of guinea pigs. PMID:20594955

  5. Downregulation of ACE2/Ang-(1-7)/Mas axis promotes breast cancer metastasis by enhancing store-operated calcium entry.

    Science.gov (United States)

    Yu, Changhui; Tang, Wei; Wang, Yuhao; Shen, Qiang; Wang, Bin; Cai, Chunqing; Meng, Xiaojing; Zou, Fei

    2016-07-01

    The renin-angiotensin system (RAS) is an important component of the tumor microenvironment and plays a key role in promoting cancer cell proliferation, angiogenesis, metabolism, migration and invasion. Meanwhile, the arm of angiotensin-converting enzyme (ACE)2/angiotensin-(1-7) [Ang-(1-7)]/Mas axis in connection with RAS is associated with anti-proliferative, vasodilatory and anti-metastatic properties. Previous studies have shown that Ang-(1-7) reduces the proliferation of orthotopic human breast tumor growth by inhibiting cancer-associated fibroblasts. However, the role of ACE/Ang-(1-7)/Mas axis in the metastasis of breast cancer cells is still unknown. In the present study, we found that ACE2 protein level is negatively correlated with the metastatic ability of breast cancer cells and breast tumor grade. Upregulation of ACE2/Ang-(1-7)/Mas axis inhibits breast cancer cell migration and invasion in vivo and in vitro. Mechanistically, ACE2/Ang-(1-7)/Mas axis activation inhibits store-operated calcium entry (SOCE) and PAK1/NF-κB/Snail1 pathways, and induces E-cadherin expression. In summary, our results demonstrate that downregulation of ACE2/Ang-(1-7)/Mas axis stimulates breast cancer metastasis through the activation of SOCE and PAK1/NF-κB/Snail1 pathways. These results provide new mechanisms by which breast cancer develop metastasis and shed light on developing novel anti-metastasis therapeutics for metastatic breast cancer by modulating ACE2/Ang-(1-7)/Mas axis. PMID:27063099

  6. Role of Scaffolding Proteins in the Regulation of TRPC-Dependent Calcium Entry.

    Science.gov (United States)

    Constantin, Bruno

    2016-01-01

    Plasma membrane ion channels, and in particular TRPC channels need a specific membrane environment and association with scaffolding, signaling, and cytoskeleton proteins in order to play their important functional role. The molecular composition of TRPC channels is an important factor in determining channel activation mechanisms. TRPC proteins are incorporated in macromolecular complexes including several key Ca(2 +) signaling proteins as well as proteins involved in vesicle trafficking, cytoskeletal interactions, and scaffolding. Evidence has been provided for association of TRPC with calmodulin (CaM), IP3R, PMCA, Gq/11, RhoA, and a variety of scaffolding proteins. The interaction between TRPC channels with adaptor proteins, determines their mode of regulation as well as their cellular localization and function. Adaptor proteins do not display any enzymatic activity but act as scaffold for the building of signaling complexes. The scaffolding proteins are involved in the assembling of these Ca(2+) signaling complexes, the correct sub-cellular localization of protein partners, and the regulation of the TRPC channelosome. In particular, these proteins, via their multiple protein-protein interaction motifs, can interact with various ion channels involved in the transmembrane potential, and membrane excitability. Scaffolding proteins are key components for the functional organization of TRPC channelosomes that serves as a platform regulating slow Ca(2+) entry, spatially and temporally controlled [Ca(2+)]i signals and Ca(2+) -dependent cellular functions. PMID:27161237

  7. Allergens stimulate store-operated calcium entry and cytokine production in airway epithelial cells.

    Science.gov (United States)

    Jairaman, Amit; Maguire, Chelsea H; Schleimer, Robert P; Prakriya, Murali

    2016-01-01

    Aberrant immune responses to environmental allergens including insect allergens from house dust mites and cockroaches contribute to allergic inflammatory diseases such as asthma in susceptible individuals. Airway epithelial cells (AECs) play a critical role in this process by sensing the proteolytic activity of allergens via protease-activated receptors (PAR2) to initiate inflammatory and immune responses in the airway. Elevation of cytosolic Ca(2+) is an important signaling event in this process, yet the fundamental mechanism by which allergens induce Ca(2+) elevations in AECs remains poorly understood. Here we find that extracts from dust mite and cockroach induce sustained Ca(2+) elevations in AECs through the activation of Ca(2+) release-activated Ca(2+) (CRAC) channels encoded by Orai1 and STIM1. CRAC channel activation occurs, at least in part, through allergen mediated stimulation of PAR2 receptors. The ensuing Ca(2+) entry then activates NFAT/calcineurin signaling to induce transcriptional production of the proinflammatory cytokines IL-6 and IL-8. These findings highlight a key role for CRAC channels as regulators of allergen induced inflammatory responses in the airway. PMID:27604412

  8. Angiotensin II activates different calcium signaling pathways in adipocytes.

    Science.gov (United States)

    Dolgacheva, Lyudmila P; Turovskaya, Maria V; Dynnik, Vladimir V; Zinchenko, Valery P; Goncharov, Nikolay V; Davletov, Bazbek; Turovsky, Egor A

    2016-03-01

    Angiotensin II (Ang II) is an important mammalian neurohormone involved in reninangiotensin system. Ang II is produced both constitutively and locally by RAS systems, including white fat adipocytes. The influence of Ang II on adipocytes is complex, affecting different systems of signal transduction from early Са(2+) responses to cell proliferation and differentiation, triglyceride accumulation, expression of adipokine-encoding genes and adipokine secretion. It is known that white fat adipocytes express all RAS components and Ang II receptors (АТ1 and АТ2). The current work was carried out with the primary white adipocytes culture, and Са(2+) signaling pathways activated by Ang II were investigated using fluorescent microscopy. Са(2+)-oscillations and transient responses of differentiated adipocytes to Ang II were registered in cells with both small and multiple lipid inclusions. Using inhibitory analysis and selective antagonists, we now show that Ang II initiates periodic Са(2+)-oscillations and transient responses by activating АТ1 and АТ2 receptors and involving branched signaling cascades:In these cascades, AT1 receptors play the leading role. The results of the present work open a perspective of using Ang II for correction of signal resistance of adipocytes often observed during obesity and type 2diabetes. PMID:26850364

  9. Blockade of store-operated calcium entry alleviates ethanol-induced hepatotoxicity via inhibiting apoptosis

    International Nuclear Information System (INIS)

    Extracellular Ca2+ influx has been suggested to play a role in ethanol-induced hepatocyte apoptosis and necrosis. Previous studies indicated that store-operated Ca2+ entry (SOCE) was involved in liver injury induced by ethanol in HepG2 cells. However, the mechanisms underlying liver injury caused by SOCE remain unclear. We aimed to investigate the effects and mechanism of SOCE inhibition on liver injury induced by ethanol in BRL cells and Sprague–Dawley rats. Our data demonstrated that ethanol (0–400 mM) dose-dependently increased hepatocyte injury and 100 mM ethanol significantly upregulated the mRNA and protein expression of SOC for at least 72 h in BRL cells. Blockade of SOCE by pharmacological inhibitors and sh-RNA knockdown of STIM1 and Orai1 attenuated intracellular Ca2+ overload, restored the mitochondrial membrane potential (MMP), decreased cytochrome C release and inhibited ethanol-induced apoptosis. STIM1 and Orai1 expression was greater in ethanol-treated than control rats, and the SOCE inhibitor corosolic acid ameliorated the histopathological findings and alanine transaminase and aspartate transaminase activity as well as decreased cytochrome C release and inhibited alcohol-induced cell apoptosis. These findings suggest that SOCE blockade could alleviate alcohol-induced hepatotoxicity via inhibiting apoptosis. SOCE might be a useful therapeutic target in alcoholic liver diseases. - Highlights: • Blockade of SOCE alleviated overload of Ca2+ and hepatotoxicity after ethanol application. • Blockade of SOCE inhibited mitochondrial apoptosis after ethanol application. • SOCE might be a useful therapeutic target in alcoholic liver diseases

  10. Blockade of store-operated calcium entry alleviates ethanol-induced hepatotoxicity via inhibiting apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Cui, Ruibing [Department of Hepatology and Gastroenterology, Qilu Hospital of Shandong University, Jinan, Shandong Province 250012 (China); Yan, Lihui [Shandong Normal University, Jinan, Shandong Province 250012 (China); Luo, Zheng; Guo, Xiaolan [Department of Hepatology and Gastroenterology, Qilu Hospital of Shandong University, Jinan, Shandong Province 250012 (China); Yan, Ming, E-mail: ymylh@163.com [Department of Hepatology and Gastroenterology, Qilu Hospital of Shandong University, Jinan, Shandong Province 250012 (China)

    2015-08-15

    Extracellular Ca{sup 2+} influx has been suggested to play a role in ethanol-induced hepatocyte apoptosis and necrosis. Previous studies indicated that store-operated Ca{sup 2+} entry (SOCE) was involved in liver injury induced by ethanol in HepG2 cells. However, the mechanisms underlying liver injury caused by SOCE remain unclear. We aimed to investigate the effects and mechanism of SOCE inhibition on liver injury induced by ethanol in BRL cells and Sprague–Dawley rats. Our data demonstrated that ethanol (0–400 mM) dose-dependently increased hepatocyte injury and 100 mM ethanol significantly upregulated the mRNA and protein expression of SOC for at least 72 h in BRL cells. Blockade of SOCE by pharmacological inhibitors and sh-RNA knockdown of STIM1 and Orai1 attenuated intracellular Ca{sup 2+} overload, restored the mitochondrial membrane potential (MMP), decreased cytochrome C release and inhibited ethanol-induced apoptosis. STIM1 and Orai1 expression was greater in ethanol-treated than control rats, and the SOCE inhibitor corosolic acid ameliorated the histopathological findings and alanine transaminase and aspartate transaminase activity as well as decreased cytochrome C release and inhibited alcohol-induced cell apoptosis. These findings suggest that SOCE blockade could alleviate alcohol-induced hepatotoxicity via inhibiting apoptosis. SOCE might be a useful therapeutic target in alcoholic liver diseases. - Highlights: • Blockade of SOCE alleviated overload of Ca{sup 2+} and hepatotoxicity after ethanol application. • Blockade of SOCE inhibited mitochondrial apoptosis after ethanol application. • SOCE might be a useful therapeutic target in alcoholic liver diseases.

  11. Modeled microgravity suppressed invasion and migration of human glioblastoma U87 cells through downregulating store-operated calcium entry

    International Nuclear Information System (INIS)

    Glioblastoma is the most common brain tumor and is characterized with robust invasion and migration potential resulting in poor prognosis. Previous investigations have demonstrated that modeled microgravity (MMG) could decline the cell proliferation and attenuate the metastasis potential in several cell lines. In this study, we studied the effects of MMG on the invasion and migration potentials of glioblastoma in human glioblastoma U87 cells. We found that MMG stimulation significantly attenuated the invasion and migration potentials, decreased thapsigargin (TG) induced store-operated calcium entry (SOCE) and downregulated the expression of Orai1 in U87 cells. Inhibition of SOCE by 2-APB or stromal interaction molecule 1 (STIM1) downregulation both mimicked the effects of MMG on the invasion and migration potentials in U87 cells. Furthermore, upregulation of Orai1 significantly weakened the effects of MMG on the invasion and migration potentials in U87 cells. Therefore, these findings indicated that MMG stimulation inhibited the invasion and migration potentials of U87 cells by downregulating the expression of Orai1 and sequentially decreasing the SOCE, suggesting that MMG might be a new potential therapeutic strategy in glioblastoma treatment in the future. - Highlights: • Modeled microgravity (MMG) suppressed migration and invasion in U87 cells. • MMG downregulated the SOCE and the expression of Orai1. • SOCE inhibition mimicked the effects of MMG on migration and invasion potentials. • Restoration of SOCE diminished the effects of MMG on migration and invasion

  12. Modeled microgravity suppressed invasion and migration of human glioblastoma U87 cells through downregulating store-operated calcium entry

    Energy Technology Data Exchange (ETDEWEB)

    Shi, Zi-xuan [Department of Traditional Chinese Medicine, Xijing Hospital, Fourth Military Medical University, Xi' an, 710032 (China); Rao, Wei [Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi' an, 710032 (China); Wang, Huan [Department of Dermatology, Tangdu Hospital, Fourth Military Medical University, Xi' an, 710032 (China); Wang, Nan-ding [Department of Cardiology, Xi' an Traditional Chinese Medicine Hospital, Xi' an, 710032 (China); Si, Jing-Wen; Zhao, Jiao; Li, Jun-chang [Department of Traditional Chinese Medicine, Xijing Hospital, Fourth Military Medical University, Xi' an, 710032 (China); Wang, Zong-ren, E-mail: zongren@fmmu.edu.cn [Department of Traditional Chinese Medicine, Xijing Hospital, Fourth Military Medical University, Xi' an, 710032 (China)

    2015-02-13

    Glioblastoma is the most common brain tumor and is characterized with robust invasion and migration potential resulting in poor prognosis. Previous investigations have demonstrated that modeled microgravity (MMG) could decline the cell proliferation and attenuate the metastasis potential in several cell lines. In this study, we studied the effects of MMG on the invasion and migration potentials of glioblastoma in human glioblastoma U87 cells. We found that MMG stimulation significantly attenuated the invasion and migration potentials, decreased thapsigargin (TG) induced store-operated calcium entry (SOCE) and downregulated the expression of Orai1 in U87 cells. Inhibition of SOCE by 2-APB or stromal interaction molecule 1 (STIM1) downregulation both mimicked the effects of MMG on the invasion and migration potentials in U87 cells. Furthermore, upregulation of Orai1 significantly weakened the effects of MMG on the invasion and migration potentials in U87 cells. Therefore, these findings indicated that MMG stimulation inhibited the invasion and migration potentials of U87 cells by downregulating the expression of Orai1 and sequentially decreasing the SOCE, suggesting that MMG might be a new potential therapeutic strategy in glioblastoma treatment in the future. - Highlights: • Modeled microgravity (MMG) suppressed migration and invasion in U87 cells. • MMG downregulated the SOCE and the expression of Orai1. • SOCE inhibition mimicked the effects of MMG on migration and invasion potentials. • Restoration of SOCE diminished the effects of MMG on migration and invasion.

  13. IgE receptor-activated calcium permeability pathway in rat basophilic leukemia cells

    International Nuclear Information System (INIS)

    When antigen-stimulated 45Ca uptake is measured in RBL cells loaded with > 3 mM quin2, re-extrusion of 45Ca is minimized and the initial rate of 45Ca uptake reflects the true unidirectional influx of Ca. This influx correlates more closely with secretion than with the number of IgE receptors aggregated by antigen. The antigen-induced permeability pathway is saturable, having a Km of about 0.7 mM and a Vmax of 0.9 nmol Ca/106 cells/min and it persists for at least an hour provided that receptor aggregation is maintained. The negatively charged fluorescent probe bis-oxonol is insensitive to changes in the mitochondrial membrane potential and is, therefore, a useful plasma membrane potential indicator. Antigen-stimulation of RBL cells equilibrated with bis-oxonol causes a rapid depolarization that peaks within 2-3 minutes and persists until receptor aggregates are disrupted. Antigen-induced depolarization is seen in the absence of extracellular calcium, but is almost completely abolished when both sodium and calcium are replaced by glucose. Addition of calcium restores this response even when sodium is absent. This suggests that the IgE receptor-activated permeability pathway has a similar conductance for sodium and calcium ions

  14. Molecular dissection of prethymic progenitor entry into the T lymphocyte developmental pathway

    Energy Technology Data Exchange (ETDEWEB)

    Fung, Elizabeth-sharon [Los Alamos National Laboratory

    2008-01-01

    Notch signaling activates T lineage differentiation from hemopoietic progenitors, but relatively few regulators that initiate this program have been identified, e.g., GATA3 and T cell factor-I (TCF-1) (gene name Tcli). To identify additional regulators of T cell specification, a cDNA libnlrY from mouse Pro-T cells was screened for genes that are specifically up-regulated in intrathymic T cell precursors as compared with myeloid progenitors. Over 90 genes of interest were identified, and 35 of 44 tested were confirmed to be more highly expressed in T lineage precursors relative to precursors of B and/or myeloid lineage. To a remarkable extent, however, expression of these T lineage-enriched genes, including zinc finger transcription factor, helicase, and signaling adaptor genes, was also shared by stem cells (Lin{sup -}Sca-1{sup +}Kit{sup +}CD27{sup -}) and multipotent progenitors (Lin{sup -}Sca-l{sup +}Kit{sup +}CD27{sup +}), although down-regulated in other lineages. Thus, a major fraction of these early T lineage genes are a regulatory legacy from stem cells. The few genes sharply up-regulated between multipotent progenitors and Pro-T cell stages included those encoding transcription factors Bclllb, TCF-I (Tcli), and HEBalt, Notch target Deltexl, Deltex3L, Fkbp5, Eval, and Tmem13l. Like GATA3 and Deltexl, Bclllb, Fkbp5, and Eval were dependent on Notch/Delta signaling for induction in fetal liver precursors, but only BcIlI band HEBalt were up-regulated between the first two stages of intrathymic T cell development (double negative I and double negative 2) corresponding to T lineage specification. Bclllb was uniquely T lineage restricted and induced by NotchlDelta signaling specifically upon entry into the T lineage differentiation pathway.

  15. Fyn kinase controls Fc{epsilon}RI receptor-operated calcium entry necessary for full degranulation in mast cells

    Energy Technology Data Exchange (ETDEWEB)

    Sanchez-Miranda, Elizabeth; Ibarra-Sanchez, Alfredo [Departamento de Farmacobiologia, Centro de Investigacion y de Estudios Avanzados (Cinvestav), Sede Sur, Calzada de los Tenorios 235, Col. Granjas Coapa, CP 14330 Mexico City (Mexico); Gonzalez-Espinosa, Claudia, E-mail: cgonzal@cinvestav.mx [Departamento de Farmacobiologia, Centro de Investigacion y de Estudios Avanzados (Cinvestav), Sede Sur, Calzada de los Tenorios 235, Col. Granjas Coapa, CP 14330 Mexico City (Mexico)

    2010-01-22

    IgE-antigen-dependent crosslinking of the high affinity IgE receptor (Fc{epsilon}RI) on mast cells leads to degranulation, leukotriene synthesis and cytokine production. Calcium (Ca{sup 2+}) mobilization is a sine qua non requisite for degranulation, allowing the rapid secretion of stored pro-inflammatory mediators responsible for allergy symptoms. Fyn is a Src-family kinase that positively controls Fc{epsilon}RI-induced mast cell degranulation. However, our understanding of the mechanism connecting Fyn activation to secretion of pre-synthesized mediators is very limited. We analyzed Fc{epsilon}RI-dependent Ca{sup 2+} mobilization in bone marrow-derived mast cells (BMMCs) differentiated from WT and Fyn -/- knock out mice. Fyn -/- BMMCs showed a marked defect in extracellular Ca{sup 2+} influx after Fc{epsilon}RI crosslinking but not after thapsigargin addition. High concentrations of Gadolinium (Gd{sup 3+}) partially blocked Fc{epsilon}RI-induced Ca{sup 2+} influx in WT cells but, in contrast, completely inhibited Ca{sup 2+} mobilization in Fyn -/- cells. Low concentrations of an inhibitor of the canonical transient receptor potential (TRPC) Ca{sup 2+} channels (2-aminoethoxyphenyl-borane, 2-APB) blocked Fc{epsilon}RI-induced maximal Ca{sup 2+} rise in WT but not in Fyn -/- cells. Ca{sup 2+} entry through Fyn-controlled, 2-APB sensitive channels was found to be important for full degranulation and IL-2 mRNA accumulation in WT cells. Immunoprecipitation assays showed that Fyn kinase interacts with TRPC 3/6/7 channels after IgE-antigen stimulation, but its association is not related to protein tyrosine phosphorylation. Results indicate Fyn kinase mediates the receptor-dependent activation of TRPC channels that contribute to degranulation in Fc{epsilon}RI-stimulated mast cells.

  16. Fyn kinase controls FcεRI receptor-operated calcium entry necessary for full degranulation in mast cells

    International Nuclear Information System (INIS)

    IgE-antigen-dependent crosslinking of the high affinity IgE receptor (FcεRI) on mast cells leads to degranulation, leukotriene synthesis and cytokine production. Calcium (Ca2+) mobilization is a sine qua non requisite for degranulation, allowing the rapid secretion of stored pro-inflammatory mediators responsible for allergy symptoms. Fyn is a Src-family kinase that positively controls FcεRI-induced mast cell degranulation. However, our understanding of the mechanism connecting Fyn activation to secretion of pre-synthesized mediators is very limited. We analyzed FcεRI-dependent Ca2+ mobilization in bone marrow-derived mast cells (BMMCs) differentiated from WT and Fyn -/- knock out mice. Fyn -/- BMMCs showed a marked defect in extracellular Ca2+ influx after FcεRI crosslinking but not after thapsigargin addition. High concentrations of Gadolinium (Gd3+) partially blocked FcεRI-induced Ca2+ influx in WT cells but, in contrast, completely inhibited Ca2+ mobilization in Fyn -/- cells. Low concentrations of an inhibitor of the canonical transient receptor potential (TRPC) Ca2+ channels (2-aminoethoxyphenyl-borane, 2-APB) blocked FcεRI-induced maximal Ca2+ rise in WT but not in Fyn -/- cells. Ca2+ entry through Fyn-controlled, 2-APB sensitive channels was found to be important for full degranulation and IL-2 mRNA accumulation in WT cells. Immunoprecipitation assays showed that Fyn kinase interacts with TRPC 3/6/7 channels after IgE-antigen stimulation, but its association is not related to protein tyrosine phosphorylation. Results indicate Fyn kinase mediates the receptor-dependent activation of TRPC channels that contribute to degranulation in FcεRI-stimulated mast cells.

  17. Microsecond Molecular Simulations Reveal a Transient Proton Pathway in the Calcium Pump.

    Science.gov (United States)

    Espinoza-Fonseca, L Michel; Ramírez-Salinas, G Lizbeth

    2015-06-10

    The calcium pump sarcoplasmic reticulum Ca(2+)-ATPase (SERCA) counter-transports Ca(2+) and H(+) at the expense of ATP hydrolysis. SERCA uses separate proton and metal ion pathways during active transport to neutralize the highly charged transport site, thus preserving SERCA's structural stability during active Ca(2+) transport. Although separate metal ion and proton pathways have been identified during slow (millisecond) structural transitions of SERCA, the existence of simultaneous metal and proton pathways during fast (microsecond) structural transitions remains unknown. We have analyzed microsecond-long trajectories of E1·H(+)771, a protonated intermediate of the pump populated during SERCA regulation. We found a transiently established hydrophobic pore in the luminal side of the transmembrane helices 6, 8, and 9. This narrow (0.5-0.6 nm) pore connects the transport sites to the sarcoplasmic reticulum lumen through a chain of water molecules. Protein pKa calculations of the transport site residues and structural analysis of the water molecules showed that this pore is suitable for proton transport. This transient proton pathway ensures neutralization of the transport sites during the rapid structural transitions associated with regulation of the pump. We conclude that this transient proton pathway plays a central role in optimizing active Ca(2+) transport by SERCA. Our discovery provides insight into ion-exchange mechanisms through transient hydrophobic pores in P-type ATPases. PMID:26028459

  18. Calcium effect on the metabolic pathway of phosphorus accumulating organisms in enhanced biological phosphorus removal systems.

    Science.gov (United States)

    Zhang, Hai-Ling; Sheng, Guo-Ping; Fang, Wei; Wang, Yong-Peng; Fang, Cai-Yun; Shao, Li-Min; Yu, Han-Qing

    2015-11-01

    Phosphorus accumulating organisms (PAOs) have been found to act as glycogen-accumulating organisms (GAOs) under certain conditions, thus, the deterioration in the performance of enhanced biological phosphorus removal systems is not always attributed to the proliferation of GAOs. In this work, the effects of calcium on the metabolic pathway of PAOs were explored. It was found that when the influent Ca(2+) concentration was elevated, the tendency and extent of extracellular calcium phosphate precipitation increased, and the intracellular inert Ca-bound polyphosphate was synthesized, while the microbial population remained almost unchanged. The changes in the ratios of phosphorus released/acetate uptaken, the glycogen degraded/acetate uptaken and the poly-β-hydroxyalkanoates synthesized/acetate uptaken during the anaerobic period confirm that, as the influent Ca(2+) concentration was increased, the polyphosphate-accumulating metabolism was partially shifted to the glycogen-accumulating metabolism. At an influent Ca(2+) around 50 mg/L, in addition to the extracellular calcium phosphate precipitation, the intracellular inert Ca-bound polyphosphate synthesis might also be involved in the metabolic change of PAOs. The results of the present work would be beneficial to better understand the biochemical metabolism of PAOs in enhanced biological phosphorus removal systems. PMID:26233656

  19. Dissecting the Cell Entry Pathway of Dengue Virus by Single-Particle Tracking in Living Cells

    NARCIS (Netherlands)

    van der Schaar, Hilde M.; Rust, Michael J.; Chen, Chen; van der Ende-Metselaar, Heidi; Wilschut, Jan; Zhuang, Xiaowei; Smit, Jolanda M.

    2008-01-01

    Dengue virus (DENV) is an enveloped RNA virus that causes the most common arthropod-borne infection worldwide. The mechanism by which DENV infects the host cell remains unclear. In this work, we used live-cell imaging and single-virus tracking to investigate the cell entry, endocytic trafficking, an

  20. Inhibition of a store-operated Ca2+ entry pathway in human endothelial cells by the isoquinoline derivative LOE 908.

    Science.gov (United States)

    Encabo, A; Romanin, C; Birke, F W; Kukovetz, W R; Groschner, K

    1996-10-01

    1. The novel cation channel blocker, LOE 908, was tested for its effects on Ca2+ entry and membrane currents activated by depletion of intracellular Ca2+ stores in human endothelial cells. 2. LOE 908 inhibited store-operated Ca2+ entry induced by direct depletion of Ca2+ stores with 100 nM thapsigargin or 100 nM ionomycin with an EC50 of 2 microM and 4 microM, respectively. 3. LOE 908 did not affect thapsigargin- or ionomycin-induced Ca2+ release from intracellular stores up to concentrations of 3 microM. 4. LOE 908 reversibly suppressed thapsigargin- as well as ionomycin-induced whole-cell membrane currents. 5. The LOE 908-sensitive membrane conductance corresponded to a cation permeability of 5.5 and 6.9 fold selectivity for Ca2+ over K+ in the presence of thapsigargin and ionomycin, respectively. 6. Our results suggest that the isoquinoline, LOE 908 is a novel, potent inhibitor of the store-operated (capacitive) Ca2+ entry pathway in endothelial cells. PMID:8904644

  1. Coronavirus cell entry occurs through the endo-/lysosomal pathway in a proteolysis-dependent manner.

    Directory of Open Access Journals (Sweden)

    Christine Burkard

    2014-11-01

    Full Text Available Enveloped viruses need to fuse with a host cell membrane in order to deliver their genome into the host cell. While some viruses fuse with the plasma membrane, many viruses are endocytosed prior to fusion. Specific cues in the endosomal microenvironment induce conformational changes in the viral fusion proteins leading to viral and host membrane fusion. In the present study we investigated the entry of coronaviruses (CoVs. Using siRNA gene silencing, we found that proteins known to be important for late endosomal maturation and endosome-lysosome fusion profoundly promote infection of cells with mouse hepatitis coronavirus (MHV. Using recombinant MHVs expressing reporter genes as well as a novel, replication-independent fusion assay we confirmed the importance of clathrin-mediated endocytosis and demonstrated that trafficking of MHV to lysosomes is required for fusion and productive entry to occur. Nevertheless, MHV was shown to be less sensitive to perturbation of endosomal pH than vesicular stomatitis virus and influenza A virus, which fuse in early and late endosomes, respectively. Our results indicate that entry of MHV depends on proteolytic processing of its fusion protein S by lysosomal proteases. Fusion of MHV was severely inhibited by a pan-lysosomal protease inhibitor, while trafficking of MHV to lysosomes and processing by lysosomal proteases was no longer required when a furin cleavage site was introduced in the S protein immediately upstream of the fusion peptide. Also entry of feline CoV was shown to depend on trafficking to lysosomes and processing by lysosomal proteases. In contrast, MERS-CoV, which contains a minimal furin cleavage site just upstream of the fusion peptide, was negatively affected by inhibition of furin, but not of lysosomal proteases. We conclude that a proteolytic cleavage site in the CoV S protein directly upstream of the fusion peptide is an essential determinant of the intracellular site of fusion.

  2. Human herpesvirus-6 entry into the central nervous system through the olfactory pathway

    OpenAIRE

    Harberts, Erin; Yao, Karen; Wohler, Jillian E.; Maric, Dragan; Ohayon, Joan; Henkin, Robert; Jacobson, Steven

    2011-01-01

    Viruses have been implicated in the development of neurodegenerative diseases, such as Alzheimer's, Parkinson’s, and multiple sclerosis. Human herpesvirus-6 (HHV-6) is a neurotropic virus that has been associated with a wide variety of neurologic disorders, including encephalitis, mesial temporal lobe epilepsy, and multiple sclerosis. Currently, the route of HHV-6 entry into the CNS is unknown. Using autopsy specimens, we found that the frequency of HHV-6 DNA in the olfactory bulb/tract regio...

  3. Integration of light signals by the retinoblastoma pathway in the control of S phase entry in the picophytoplanktonic cell Ostreococcus.

    Directory of Open Access Journals (Sweden)

    Mickael Moulager

    2010-05-01

    Full Text Available Although the decision to proceed through cell division depends largely on the metabolic status or the size of the cell, the timing of cell division is often set by internal clocks such as the circadian clock. Light is a major cue for circadian clock entrainment, and for photosynthetic organisms it is also the main source of energy supporting cell growth prior to cell division. Little is known about how light signals are integrated in the control of S phase entry. Here, we present an integrated study of light-dependent regulation of cell division in the marine green alga Ostreococcus. During early G1, the main genes of cell division were transcribed independently of the amount of light, and the timing of S phase did not occur prior to 6 hours after dawn. In contrast S phase commitment and the translation of a G1 A-type cyclin were dependent on the amount of light in a cAMP-dependent manner. CyclinA was shown to interact with the Retinoblastoma (Rb protein during S phase. Down-regulating Rb bypassed the requirement for CyclinA and cAMP without altering the timing of S phase. Overexpression of CyclinA overrode the cAMP-dependent control of S phase entry and led to early cell division. Therefore, the Rb pathway appears to integrate light signals in the control of S phase entry in Ostreococcus, though differential transcriptional and posttranscriptional regulations of a G1 A-type cyclin. Furthermore, commitment to S phase depends on a cAMP pathway, which regulates the synthesis of CyclinA. We discuss the relative involvements of the metabolic and time/clock signals in the photoperiodic control of cell division.

  4. Regulation of intracellular calcium in resting and stimulated rat basophilic leukemia cells

    International Nuclear Information System (INIS)

    Intracellular calcium regulation was studied in a cell line of mast cells, the rat basophilic leukemia (RBL) cells with the purpose of determining (1) The properties of the plasma membrane calcium permeability pathway and (2) The role of intracellular calcium stores. The first set of experiments showed that depolarization did not induce calcium entry or secretion in resting cells and did inhibit antigen-stimulated calcium uptake and secretion. In the second set of experiments the ionic basis of antigen-induced depolarization was studied using the fluorescent potential-sensitive probe bis-oxonol. The properties of the calcium entry pathway were more consistent with a calcium channel than a calcium transport mechanism such as Na:Ca exchange. The third set of experiments examined the effects of the proton ionophore carbonyl cyanide m-chlorophenylhydrazone (CCCP) on RBL cells. CCCP inhibited antigen-stimulated 45Ca uptake and secretion by depolarizing the plasma membrane

  5. Activation of intracellular calcium by multiple Wnt ligands and translocation of β-catenin into the nucleus: a convergent model of Wnt/Ca2+ and Wnt/β-catenin pathways.

    Science.gov (United States)

    Thrasivoulou, Christopher; Millar, Michael; Ahmed, Aamir

    2013-12-13

    Ca(2+) and β-catenin, a 92-kDa negatively charged transcription factor, transduce Wnt signaling via the non-canonical, Wnt/Ca(2+) and canonical, Wnt/β-catenin pathways independently. The nuclear envelope is a barrier to large protein entry, and this process is regulated by intracellular calcium [Ca(2+)]i and trans-nuclear potential. How β-catenin traverses the nuclear envelope is not well known. We hypothesized that Wnt/Ca(2+) and Wnt/β-catenin pathways act in a coordinated manner and that [Ca(2+)]i release facilitates β-catenin entry into the nucleus in mammalian cells. In a live assay using calcium dyes in PC3 prostate cancer cells, six Wnt peptides (3A, 4, 5A, 7A, 9B, and 10B) mobilized [Ca(2+)]i but Wnt11 did not. Based upon dwell time (range = 15-30 s) of the calcium waveform, these Wnts could be classified into three classes: short, 3A and 5A; long, 7A and 10B; and very long, 4 and 9B. Wnt-activated [Ca(2+)]i release was followed by an increase in intranuclear calcium and the depolarization of both the cell and nuclear membranes, determined by using FM4-64. In cells treated with Wnts 5A, 9B, and 10B, paradigm substrates for each Wnt class, increased [Ca(2+)]i was followed by β-catenin translocation into the nucleus in PC3, MCF7, and 253J, prostate, breast, and bladder cancer cell lines; both the increase in Wnt 5A, 9B, and 10B induced [Ca(2+)]i release and β-catenin translocation are suppressed by thapsigargin in PC3 cell line. We propose a convergent model of Wnt signaling network where Ca(2+) and β-catenin pathways may act in a coordinated, interdependent, rather than independent, manner. PMID:24158438

  6. Multiple signaling pathways mediated by dopamine and calcium ionophore A23187 in human platelets

    International Nuclear Information System (INIS)

    This study was undertaken to investigate the mechanism(s) of platelet aggregation induced by the synergistic action of dopamine (DA) and a Ca/sup +2/-ionophore, A23187. DA showed non significant effect on platelet aggregation over a wide range of concentrations (up to 500 micro M), but did potentiate the aggregation response of A23187. Aggregation induced by A23187 was inhibited by calcium channel blockers (diltiazem and verpamil), receptor blockers (chlorpromazine and haloperidol) and a cyclo-oxygenase inhibitor (indomethacin). However, the inhibitory effect of these blockers was more pronounced (with a selectivity ratio of 1.5-28) in the aggregation induced by synergistic effect of A23187 and DA. A phosphatidylinositol 3-kinase (P1 3-Kinase) inhibitor, wortmanin (1C/sub 50/. 25-30 nM), inhibited aggregation induced by either A23187 or DA and act synergistically. This synergistic effect on platelet aggregation is mediated through multiple signaling pathways. (author)

  7. The pore-forming toxin listeriolysin O mediates a novel entry pathway of L. monocytogenes into human hepatocytes.

    Directory of Open Access Journals (Sweden)

    Stephen Vadia

    2011-11-01

    Full Text Available Intracellular pathogens have evolved diverse strategies to invade and survive within host cells. Among the most studied facultative intracellular pathogens, Listeria monocytogenes is known to express two invasins-InlA and InlB-that induce bacterial internalization into nonphagocytic cells. The pore-forming toxin listeriolysin O (LLO facilitates bacterial escape from the internalization vesicle into the cytoplasm, where bacteria divide and undergo cell-to-cell spreading via actin-based motility. In the present study we demonstrate that in addition to InlA and InlB, LLO is required for efficient internalization of L. monocytogenes into human hepatocytes (HepG2. Surprisingly, LLO is an invasion factor sufficient to induce the internalization of noninvasive Listeria innocua or polystyrene beads into host cells in a dose-dependent fashion and at the concentrations produced by L. monocytogenes. To elucidate the mechanisms underlying LLO-induced bacterial entry, we constructed novel LLO derivatives locked at different stages of the toxin assembly on host membranes. We found that LLO-induced bacterial or bead entry only occurs upon LLO pore formation. Scanning electron and fluorescence microscopy studies show that LLO-coated beads stimulate the formation of membrane extensions that ingest the beads into an early endosomal compartment. This LLO-induced internalization pathway is dynamin-and F-actin-dependent, and clathrin-independent. Interestingly, further linking pore formation to bacteria/bead uptake, LLO induces F-actin polymerization in a tyrosine kinase-and pore-dependent fashion. In conclusion, we demonstrate for the first time that a bacterial pathogen perforates the host cell plasma membrane as a strategy to activate the endocytic machinery and gain entry into the host cell.

  8. All-trans retinoic acid promotes neural lineage entry by pluripotent embryonic stem cells via multiple pathways

    Directory of Open Access Journals (Sweden)

    Fang Bo

    2009-07-01

    Full Text Available Abstract Background All-trans retinoic acid (RA is one of the most important morphogens with pleiotropic actions. Its embryonic distribution correlates with neural differentiation in the developing central nervous system. To explore the precise effects of RA on neural differentiation of mouse embryonic stem cells (ESCs, we detected expression of RA nuclear receptors and RA-metabolizing enzymes in mouse ESCs and investigated the roles of RA in adherent monolayer culture. Results Upon addition of RA, cell differentiation was directed rapidly and exclusively into the neural lineage. Conversely, pharmacological interference with RA signaling suppressed this neural differentiation. Inhibition of fibroblast growth factor (FGF signaling did not suppress significantly neural differentiation in RA-treated cultures. Pharmacological interference with extracellular signal-regulated kinase (ERK pathway or activation of Wnt pathway effectively blocked the RA-promoted neural specification. ERK phosphorylation was enhanced in RA-treated cultures at the early stage of differentiation. Conclusion RA can promote neural lineage entry by ESCs in adherent monolayer culture systems. This effect depends on RA signaling and its crosstalk with the ERK and Wnt pathways.

  9. The caveolae-mediated sv40 entry pathway bypasses the golgi complex en route to the endoplasmic reticulum

    Directory of Open Access Journals (Sweden)

    Kuksin Dmitry

    2005-04-01

    Full Text Available Abstract Background Simian virus 40 (SV40 enters cells via an atypical caveolae-mediated endocytic pathway, which delivers the virus to a new intermediary compartment, the caveosome. The virus then is believed to go directly from the caveosome to the endoplasmic reticulum. Cholera toxin likewise enters via caveolae and traffics to caveosomes. But, in contrast to SV40, cholera toxin is transported from caveosomes to the endoplasmic reticulum via the Golgi. For that reason, and because the caveosome and Golgi may have some common markers, we revisited the issue of whether SV40 might access the endoplasmic reticulum via the Golgi. Results We confirmed our earlier finding that SV40 co localizes with the Golgi marker β-COP. However, we show that the virus does not co localize with the more discriminating Golgi markers, golgin 97 and BODIPY-ceramide. Conclusion The caveolae-mediated SV40 entry pathway does not intersect the Golgi. SV40 is seen to co localize with β-COP because that protein is a marker for caveosomes as well as the Golgi. Moreover, these results are consistent with the likelihood that the caveosome is a sorting organelle. In addition, there are at least two distinct but related routes by which a ligand might traffic from the caveosome to the ER; one route involving transport through the Golgi, and another pathway that does not involve the Golgi.

  10. Entry and exit pathways of CO2 in rat liver mitochondria respiring in a bicarbonate buffer system.

    Science.gov (United States)

    Balboni, E; Lehninger, A L

    1986-03-15

    The dynamics and pathways of CO2 movements across the membranes of mitochondria respiring in vitro in a CO2/HCO-3 buffer at concentrations close to that in intact rat tissues were continuously monitored with a gas-permeable CO2-sensitive electrode. O2 uptake and pH changes were monitored simultaneously. Factors affecting CO2 entry were examined under conditions in which CO2 uptake was coupled to electrophoretic influx of K+ (in the presence of valinomycin) or Ca2+. The role of mitochondrial carbonic anhydrase (EC 4.2.1.1) in CO2 entry was evaluated by comparison of CO2 uptake by rat liver mitochondria, which possess carbonic anhydrase, versus rat heart mitochondria, which lack carbonic anhydrase. Such studies showed that matrix carbonic anhydrase activity is essential for rapid net uptake of CO2 with K+ or Ca2+. Studies with acetazolamide (Diamox), a potent inhibitor of carbonic anhydrase, confirmed the requirement of matrix carbonic anhydrase for net CO2 uptake. It was shown that at pH 7.2 the major species leaving respiring mitochondria is dissolved CO2, rather than HCO-3 or H2CO3 suggested by earlier reports. Efflux of endogenous CO2/HCO-3 is significantly inhibited by inhibitors of the dicarboxylate and tricarboxylate transport systems of the rat liver inner membrane. The possibility that these anion carriers mediate outward transport of HCO-3 is discussed. PMID:3081508

  11. Effect of calcium on strawberry fruit flavonoid pathway gene expression and anthocyanin accumulation.

    Science.gov (United States)

    Xu, Wenping; Peng, Hui; Yang, Tianbao; Whitaker, Bruce; Huang, Luhong; Sun, Jianghao; Chen, Pei

    2014-09-01

    Two diploid woodland strawberry (Fragaria vesca) inbred lines, Ruegen F7-4 (red fruit-bearing) and YW5AF7 (yellow fruit-bearing) were used to study the regulation of anthocyanin biosynthesis in fruit. Ruegen F7-4 fruit had similar total phenolics and anthocyanin contents to commercial octoploid (F. × ananassa) cultivar Seascape, while YW5AF7 exhibited relatively low total phenolics content and no anthocyanin accumulation. Foliar spray of CaCl2 boosted fruit total phenolics content, especially anthocyanins, by more than 20% in both Seascape and RF7-4. Expression levels of almost all the flavonoid pathway genes were comparable in Ruegen F7-4 and YW5AF7 green-stage fruit. However, at the turning and ripe stages, key anthocyanin structural genes, including flavanone 3-hydroxylase (F3H1), dihydroflavonol 4-reductase (DFR2), anthocyanidin synthase (ANS1), and UDP-glucosyltransferase (UGT1), were highly expressed in Ruegen F7-4 compared with YW5AF7 fruit. Calcium treatment further stimulated the expression of those genes in Ruegen F7-4 fruit. Anthocyanins isolated from petioles of YW5AF7 and Ruegen F-7 had the same HPLC-DAD profile, which differed from that of Ruegen F-7 fruit anthocyanins. All the anthocyanin structural genes except FvUGT1 were detected in petioles of YW5AF7 and Ruegen F-7. Taken together, these results indicate that the "yellow" gene in YW5AF7 is a fruit specific regulatory gene(s) for anthocyanin biosynthesis. Calcium can enhance accumulation of anthocyanins and total phenolics in fruit possibly via upregulation of anthocyanin structural genes. Our results also suggest that the anthocyanin biosynthesis machinery in petioles is different from that in fruit. PMID:25036468

  12. Preparing nano-calcium phosphate particles via a biologically friendly pathway

    Energy Technology Data Exchange (ETDEWEB)

    Hu Qinghong; Xu Xurong; Tang Ruikang [Department of Chemistry and Centre of Biopathways and Biomaterials, Zhejiang University, Hangzhou, Zhejang 310027 (China); Ji Huijiao; Liu Yukan; Zhang Ming, E-mail: rtang@zju.edu.c [Department of Biology, Zhejiang University, Hangzhou, Zhejiang 310058 (China)

    2010-08-01

    It is widely agreed that nano-calcium phosphates (CaP) play an important role in tissue engineering and medical application due to their unique biological characteristics. However, the properties of nano-CaP, including bioactivity, biocompatibility and mechanical properties, are tailored over wide ranges by controlling the size and morphology of particles. Therefore, it is important to develop synthesis methods which can control the particle size distribution and shape uniformly. In this study, we report that polyacrylic acid (PAA) can act as an efficient agent to modulate nano-CaP formation. The dimension of the resultant sphere-like nanoparticles (5-60 nm) can readily be regulated by changing PAA concentrations (75-200 {mu}g ml{sup -1}). In contrast to other additives, PAA is a water-soluble polymer that has already been used as an excellent biocompatible implant material in vivo. Our in vitro proliferation experiments of bone marrow mesenchymal stem cells (BMSCs) demonstrate that the involvement of PAA does not change the bioactivity of the resultant nano-CaP. In contrast, the nano-CaP fabricated by using another typical control agent, hexadecyl (cetyl) trimethyl ammonium bromide, suppressed the cell proliferation of BMSCs. Thus, we suggest that the biopolymer, PAA, can provide a more biologically friendly pathway to prepare biological nano-CaP for biomedical application. (communication)

  13. Preparing nano-calcium phosphate particles via a biologically friendly pathway

    International Nuclear Information System (INIS)

    It is widely agreed that nano-calcium phosphates (CaP) play an important role in tissue engineering and medical application due to their unique biological characteristics. However, the properties of nano-CaP, including bioactivity, biocompatibility and mechanical properties, are tailored over wide ranges by controlling the size and morphology of particles. Therefore, it is important to develop synthesis methods which can control the particle size distribution and shape uniformly. In this study, we report that polyacrylic acid (PAA) can act as an efficient agent to modulate nano-CaP formation. The dimension of the resultant sphere-like nanoparticles (5-60 nm) can readily be regulated by changing PAA concentrations (75-200 μg ml-1). In contrast to other additives, PAA is a water-soluble polymer that has already been used as an excellent biocompatible implant material in vivo. Our in vitro proliferation experiments of bone marrow mesenchymal stem cells (BMSCs) demonstrate that the involvement of PAA does not change the bioactivity of the resultant nano-CaP. In contrast, the nano-CaP fabricated by using another typical control agent, hexadecyl (cetyl) trimethyl ammonium bromide, suppressed the cell proliferation of BMSCs. Thus, we suggest that the biopolymer, PAA, can provide a more biologically friendly pathway to prepare biological nano-CaP for biomedical application. (communication)

  14. Oxethazaine inhibits hepatitis B virus capsid assembly by blocking the cytosolic calcium-signalling pathway.

    Science.gov (United States)

    Zhang, Lin; Liu, Chunlan; Xiao, Yu; Chen, Xulin

    2016-05-01

    Chronic hepatitis B virus (HBV) infection is a serious public health problem and may progress to liver fibrosis, cirrhosis and hepatocellular carcinoma. It is currently treated with PEGylated IFN-α2a and nucleoside/nucleotide analogues (NAs). However, PEGylated IFN treatment has problems of high cost, low efficiency and side effects. Long-term administration of NAs is necessary to avoid virus relapse, which can cause drug resistance and side effects. New efforts are now being directed to develop novel anti-HBV drugs targeting either additional viral targets other than viral DNA polymerase or host targets to improve the treatment of chronic hepatitis B. In this study, we discovered that oxethazaine, approved for clinic use in a few countries such as Japan, India, South Africa and Brazil, can dose-dependently reduce the levels of HBV envelope antigen, extracellular HBV DNA in supernatants and intracellular HBV total DNA. However, the levels of HBV cccDNA and HBV RNAs were not affected by oxethazaine treatment. Further study confirmed that oxethazaine acts on the virus assembly stage of the HBV life cycle. A study of the mechanisms of oxethazaine suggested that this drug inhibits HBV replication and capsid assembly by blocking the cytosolic calcium-signalling pathway. Moreover, oxethazaine could inhibit the replication of lamivudine/entecavir-dual-resistant and adefovir-resistant HBV mutants. In conclusion, our study suggests that oxethazaine may serve as a promising drug, or could be used as a starting point for anti-HBV drug discovery. PMID:26838678

  15. TRPV1 mediates cell death in rat synovial fibroblasts through calcium entry-dependent ROS production and mitochondrial depolarization

    International Nuclear Information System (INIS)

    Synoviocyte hyperplasia is critical for rheumatoid arthritis, therefore, potentially an important target for therapeutics. It was found in this work that a TRPV1 agonist capsaicin, and acidic solution (pH 5.5) induced increases in cytosolic calcium concentration ([Ca2+]c) and reactive oxygen species (ROS) production in synoviocytes isolated from a rat model of collagen-induced arthritis. The increases in both [Ca2+]c and ROS production were completely abolished in calcium-free buffer or by a TRPV1 antagonist capsazepine. Further experiments revealed that capsaicin and pH 5.5 solution caused mitochondrial membrane depolarization and reduction in cell viability; such effects were inhibited by capsazepine, or the NAD(P)H oxidase inhibitor diphenylene iodonium. Both capsaicin and pH 5.5 buffer induced apoptosis as shown by nuclear condensation and fragmentation. Furthermore, RT-PCR readily detected TRPV1 mRNA expression in the isolated synoviocytes. Taken together, these data indicated that TRPV1 activation triggered synoviocyte death by [Ca2+]c elevation, ROS production, and mitochondrial membrane depolarization

  16. High glucose enhances transient receptor potential channel canonical type 6-dependent calcium influx in human platelets via phosphatidylinositol 3-kinase-dependent pathway

    DEFF Research Database (Denmark)

    Liu, Daoyan; Maier, Alexandra; Scholze, Alexandra; Rauch, Ursula; Boltzen, Ulrike; Zhao, Zhigang; Zhu, Zhiming; Tepel, Martin

    2008-01-01

    Transient receptor potential canonical type 6 (TRPC6) channels mediating 1-oleoyl-2-acetyl-sn-glycerol (OAG)-induced calcium entry have been identified on human platelets. In the present study we tested the hypothesis that hyperglycemia increases the expression of TRPC6 channels....

  17. Disruption of the vacuolar calcium-ATPases in arabidopsis results in the activation of a salicylic acid-dependent programmed cell death pathway

    Science.gov (United States)

    Calcium (Ca2+) signals regulate many aspects of plant development, including the Hypersensitive Response (HR) that triggers a programmed cell death response to protect a plant from a pathogen. A transient increase in cytosolic Ca2+ ([Ca2+]cyt ) results from Ca2+ entry from the apoplast or release fr...

  18. Preventive effects of imperatorin on perfluorohexanesulfonate-induced neuronal apoptosis via inhibition of intracellular calcium-mediated ERK pathway.

    Science.gov (United States)

    Lee, Eunkyung; Choi, So-Young; Yang, Jae-Ho; Lee, Youn Ju

    2016-07-01

    Early life neuronal exposure to environmental toxicants has been suggested to be an important etiology of neurodegenerative disease development. Perfluorohexanesulfonate (PFHxS), one of the major perfluoroalkyl compounds, is widely distributed environmental contaminants. We have reported that PFHxS induces neuronal apoptosis via ERK-mediated pathway. Imperatorin is a furanocoumarin found in various edible plants and has a wide range of pharmacological effects including neuroprotection. In this study, the effects of imperatorin on PFHxS-induced neuronal apoptosis and the underlying mechanisms are examined using cerebellar granule cells (CGC). CGC were isolated from seven-day old rats and were grown in culture for seven days. Caspase-3 activity and TUNEL staining were used to determine neuronal apoptosis. PFHxS-induced apoptosis of CGC was significantly reduced by imperatorin and PD98059, an ERK pathway inhibitor. PFHxS induced a persistent increase in intracellular calcium, which was significantly blocked by imperatorin, NMDA receptor antagonist, MK801 and the L-type voltage-dependent calcium channel blockers, diltiazem and nifedipine. The activation of caspase-3 by PFHxS was also inhibited by MK801, diltiazem and nifedipine. PFHxS-increased ERK activation was inhibited by imperatorin, MK801, diltiazem and nifedipine. Taken together, imperatorin protects CGC against PFHxS-induced apoptosis via inhibition of NMDA receptor/intracellular calcium-mediated ERK pathway. PMID:27382356

  19. Facilitation of plateau potentials in turtle motoneurones by a pathway dependent on calcium and calmodulin

    DEFF Research Database (Denmark)

    Perrier, J F; Mejia-Gervacio, S; Hounsgaard, J

    2000-01-01

    1. The involvement of intracellular calcium and calmodulin in the modulation of plateau potentials in motoneurones was investigated using intracellular recordings from a spinal cord slice preparation. 2. Chelation of intracellular calcium with BAPTA-AM or inactivation of calmodulin with W-7 or tr...

  20. Mitochondrial calcium uniporter MCU supports cytoplasmic Ca2+ oscillations, store-operated Ca2+ entry and Ca2+-dependent gene expression in response to receptor stimulation.

    Directory of Open Access Journals (Sweden)

    Krishna Samanta

    Full Text Available Ca2+ flux into mitochondria is an important regulator of cytoplasmic Ca2+ signals, energy production and cell death pathways. Ca2+ uptake can occur through the recently discovered mitochondrial uniporter channel (MCU but whether the MCU is involved in shaping Ca2+ signals and downstream responses to physiological levels of receptor stimulation is unknown. Here, we show that modest stimulation of leukotriene receptors with the pro-inflammatory signal LTC4 evokes a series of cytoplasmic Ca2+ oscillations that are rapidly and faithfully propagated into mitochondrial matrix. Knockdown of MCU or mitochondrial depolarisation, to reduce the driving force for Ca2+ entry into the matrix, prevents the mitochondrial Ca2+ rise and accelerates run down of the oscillations. The loss of cytoplasmic Ca2+ oscillations appeared to be a consequence of enhanced Ca2+-dependent inactivation of InsP3 receptors, which arose from the loss of mitochondrial Ca2+ buffering. Ca2+ dependent gene expression in response to leukotriene receptor activation was suppressed following knockdown of the MCU. In addition to buffering Ca2+ release, mitochondria also sequestrated Ca2+ entry through store-operated Ca2+ channels and this too was prevented following loss of MCU. MCU is therefore an important regulator of physiological pulses of cytoplasmic Ca2+.

  1. Calcium Signaling Pathway Genes RUNX2 and CACNA1C Are Associated With Calcific Aortic Valve Disease

    Science.gov (United States)

    Guauque-Olarte, Sandra; Messika-Zeitoun, David; Droit, Arnaud; Lamontagne, Maxime; Tremblay-Marchand, Joël; Lavoie-Charland, Emilie; Gaudreault, Nathalie; Arsenault, Benoit J.; Dubé, Marie-Pierre; Tardif, Jean-Claude; Body, Simon C.; Seidman, Jonathan G.; Boileau, Catherine; Mathieu, Patrick; Pibarot, Philippe; Bossé, Yohan

    2016-01-01

    Background Calcific aortic valve stenosis (AS) is a life-threatening disease with no medical therapy. The genetic architecture of AS remains elusive. This study combines genome-wide association studies, gene expression, and expression quantitative trait loci mapping in human valve tissues to identify susceptibility genes of AS. Methods and Results A meta-analysis was performed combining the results of 2 genome-wide association studies in 474 and 486 cases from Quebec City (Canada) and Paris (France), respectively. Corresponding controls consisted of 2988 and 1864 individuals with European ancestry from the database of genotypes and phenotypes. mRNA expression levels were evaluated in 9 calcified and 8 normal aortic valves by RNA sequencing. The results were integrated with valve expression quantitative trait loci data obtained from 22 AS patients. Twenty-five single-nucleotide polymorphisms had Pmeta-analysis. The calcium signaling pathway was the top gene set enriched for genes mapped to moderately AS-associated single-nucleotide polymorphisms. Genes in this pathway were found differentially expressed in valves with and without AS. Two single-nucleotide polymorphisms located in RUNX2 (runt-related transcription factor 2), encoding an osteogenic transcription factor, demonstrated some association with AS (genome-wide association studies P=5.33×10−5). The mRNA expression levels of RUNX2 were upregulated in calcified valves and associated with eQTL-SNPs. CACNA1C encoding a subunit of a voltage-dependent calcium channel was upregulated in calcified valves. The eQTL-SNP with the most significant association with AS located in CACNA1C was associated with higher expression of the gene. Conclusions This integrative genomic study confirmed the role of RUNX2 as a potential driver of AS and identified a new AS susceptibility gene, CACNA1C, belonging to the calcium signaling pathway. PMID:26553695

  2. Elevating calcium in Th2 cells activates multiple pathways to induce IL-4 transcription and mRNA stabilization

    OpenAIRE

    Guo, Liying; Joseph F. Urban; Zhu, Jinfang; Paul, William E.

    2008-01-01

    PMA and ionomycin cause T cell cytokine production. We report that ionomycin alone induces IL-4 and IFNγ, but not IL-2, from in vivo and in vitro generated murine Th2 and Th1 cells. Ionomycin-induced cytokine production requires nuclear factor of activated T cells (NFAT), p38; and calmodulin-dependent kinase IV (CaMKIV). Ionomycin induces p38 phosphorylation through a calcium-dependent, cyclosporine A-inhibitable pathway. “Knocking-down” apoptosis signal-regulating kinase 1 (ASK1) inhibits io...

  3. Source identification and entry pathways of banned antibiotics nitrofuran and chloramphenicol in shrimp value chain of Bangladesh

    Directory of Open Access Journals (Sweden)

    M. Jakiul Islam

    2014-11-01

    Full Text Available Background: Contamination with residues of banned carcinogenic antibiotic drugs like nitrofuran metabolites and chloramphenicol (CAP in frozen shrimp products has become a major concern of food safety for exporting countries. In the present study an approach was taken to identify the sources of such harmful antibiotics in the shrimp value chain of Bangladesh, one of the major shrimp countries. Materials and Methods: Inputs of farms and hatchery systems including feed, feed additives, feed ingredients and therapeutic agents were thought to be the sources of contagion. Fish and shrimp feed, feed ingredients, sediment and water samples of shrimp hatcheries and farms were, therefore, analyzed for 3-Amino-5-morpholinomethyl-2-oxazolidinone (AMOZ, 3-Amino-2-oxazolidinone (AOZ, 1-Amino-hydantoin (AHD, Semicarbazide (SEM and chloramphenicol (CAP to identify their source and entry pathways. About 500 g of each 160 feed and feed ingredients were collected in pyrogens free polyethylene sealed bag and transported to Fish Inspection and Quality Control (FIQC laboratory, Dhaka, Bangladesh. Whereas 500 mL of each 250 soils and water sample were collected from hatcheries. Sample preparation and residual metabolites analysis were conducted using validated liquid chromatography-tandem mass spectrometry (LC-MS/MS analytical assays on an Waters Alliance 2695 series HPLC and Quattro Micro, API mass spectrometer instrumentation (Waters Corporation, USA. Results: Among the analyzed 160 feed samples, 38 were found contaminated with CAP and/or nitrofuran metabolites (AMOZ, AOZ, AHD and SEM, where 11, 10, 8, and 9 samples were for shrimp feed, fish feed, poultry feed and feed ingredients. Imported feed ingredients contained with protein concentrates of improper quality were found contaminate with higher level of SEM. Although hatcheries were found free from contamination, whereas sediment and water samples of many shrimp farms were found contaminated with high levels of

  4. Maturation of calcium-dependent GABA, glycine, and glutamate release in the glycinergic MNTB-LSO pathway.

    Directory of Open Access Journals (Sweden)

    Javier Alamilla

    Full Text Available The medial nucleus of the trapezoid body (MNTB is a key nucleus in high-fidelity temporal processing that underlies sound localization in the auditory brainstem. While the glycinergic principal cells of the MNTB project to all primary nuclei of the superior olive, during development the projection from MNTB to the lateral superior olive (LSO is of interest because this immature inhibitory projection is known to undergo tonotopic refinement during an early postnatal period, and because during this period individual MNTB terminals in the LSO transiently release glycine GABA and glutamate. Developmental changes in calcium-dependent release are understood to be required to allow various auditory nuclei to follow high frequency activity; however, little is known about maturation of calcium-dependent release in the MNTB-LSO pathway, which has been presumed to have less stringent requirements for high-fidelity temporal following. In acute brainstem slices of rats age postnatal day 1 to 15 we recorded whole-cell responses in LSO principal neurons to electrical stimulation in the MNTB in order to measure sensitivity to external calcium, the contribution of different voltage-gated calcium channel subtypes to vesicular release, and the maturation of these measures for both GABA/glycine and glutamate transmission. Our results establish that release of glutamate at MNTB-LSO synapses is calcium-dependent. Whereas no significant developmental changes were evident for glutamate release, GABA/glycine release underwent substantial changes over the first two postnatal weeks: soon after birth L-type, N-type, and P/Q-type voltage-gated calcium channels (VGCCs together mediated release, but after hearing onset P/Q-type VGCCs predominated. Blockade of P/Q-type VGCCs reduced the estimated quantal number for GABA/gly and glutamate transmission at P5-8 and the frequency of evoked miniature glycinergic events at P12-15, without apparent effects on spontaneous release of

  5. Identification of a Calcium Signalling Pathway of S-[6]-Gingerol in HuH-7 Cells

    Directory of Open Access Journals (Sweden)

    Xiao-Hong Li

    2013-01-01

    Full Text Available Calcium signals in hepatocytes control cell growth, proliferation, and death. Members of the transient receptor potential (TRP cation channel superfamily are candidate calcium influx channels. NFκB activation strictly depends on calcium influx and often induces antiapoptotic genes favouring cell survival. Previously, we reported that S-[6]-gingerol is an efficacious agonist of the transient receptor potential cation channel subfamily V member 1 (TRPV1 in neurones. In this study, we tested the effect of S-[6]-gingerol on HuH-7 cells using the Fluo-4 calcium assay, RT-qPCR, transient cell transfection, and luciferase measurements. We found that S-[6]-gingerol induced a transient rise in [Ca2+]i in HuH-7 cells. The increase in [Ca2+]i induced by S-[6]-gingerol was abolished by preincubation with EGTA and was also inhibited by the TRPV1 channel antagonist capsazepine. Expression of TRPV1 in HuH-7 cells was confirmed by mRNA analysis as well as a test for increase of [Ca2+]i by TRPV1 agonist capsaicin and its inhibition by capsazepine. We found that S-[6]-gingerol induced rapid NFκB activation through TRPV1 in HuH-7 cells. Furthermore, S-[6]-gingerol-induced NFκB activation was dependent on the calcium gradient and TRPV1. The rapid NFκB activation by S-[6]-gingerol was associated with an increase in mRNA levels of NFκB-target genes: cIAP-2, XIAP, and Bcl-2 that encode antiapoptotic proteins.

  6. Inhibition of a store-operated Ca2+ entry pathway in human endothelial cells by the isoquinoline derivative LOE 908.

    OpenAIRE

    Encabo, A.; Romanin, C; Birke, F. W.; Kukovetz, W. R.; Groschner, K

    1996-01-01

    1. The novel cation channel blocker, LOE 908, was tested for its effects on Ca2+ entry and membrane currents activated by depletion of intracellular Ca2+ stores in human endothelial cells. 2. LOE 908 inhibited store-operated Ca2+ entry induced by direct depletion of Ca2+ stores with 100 nM thapsigargin or 100 nM ionomycin with an EC50 of 2 microM and 4 microM, respectively. 3. LOE 908 did not affect thapsigargin- or ionomycin-induced Ca2+ release from intracellular stores up to concentrations...

  7. Pharmacologic study of calcium influx pathways in rabbit aortic smooth muscle

    International Nuclear Information System (INIS)

    Functional characteristics and pharmacologic domains of receptor-operated and potential-sensitive calcium (Ca2+) channels (ROCs and PSCs, respectively) were derived via measurements of 45Ca2+ influx (M/sup Ca/) during activation by the neurotransmitters norepinephrine (NE), histamine (HS), and serotonin (5-HT) and by elevated extracellular potassium (K+) in the individual or combined presence of organic Ca2+ channel antagonists (CAts), calmodulin antagonists (Calm-ants), lanthanum (La3+), and agents that increase intracellular levels of cyclic AMP

  8. Cross-Talk between Signaling Pathways Can Generate Robust Oscillations in Calcium and cAMP

    OpenAIRE

    Siso-Nadal, Fernando; Fox, Jeffrey J.; Laporte, Stéphane A.; Hébert, Terence E.; Swain, Peter S

    2009-01-01

    Background To control and manipulate cellular signaling, we need to understand cellular strategies for information transfer, integration, and decision-making. A key feature of signal transduction is the generation of only a few intracellular messengers by many extracellular stimuli. Methodology/Principal Findings Here we model molecular cross-talk between two classic second messengers, cyclic AMP (cAMP) and calcium, and show that the dynamical complexity of the response of both messengers inc...

  9. Calcium-containing phosphopeptides pave the secretory pathway for efficient protein traffic and secretion in fungi

    OpenAIRE

    Martín, Juan F.

    2014-01-01

    Casein phosphopeptides (CPPs) containing chelated calcium drastically increase the secretion of extracellular homologous and heterologous proteins in filamentous fungi. Casein phosphopeptides released by digestion of alpha − and beta-casein are rich in phosphoserine residues (SerP). They stimulate enzyme secretion in the gastrointestinal tract and enhance the immune response in mammals, and are used as food supplements. It is well known that casein phosphopeptides transport Ca2+ across the me...

  10. Cross-talk between signaling pathways can generate robust oscillations in calcium and cAMP.

    Directory of Open Access Journals (Sweden)

    Fernando Siso-Nadal

    Full Text Available BACKGROUND: To control and manipulate cellular signaling, we need to understand cellular strategies for information transfer, integration, and decision-making. A key feature of signal transduction is the generation of only a few intracellular messengers by many extracellular stimuli. METHODOLOGY/PRINCIPAL FINDINGS: Here we model molecular cross-talk between two classic second messengers, cyclic AMP (cAMP and calcium, and show that the dynamical complexity of the response of both messengers increases substantially through their interaction. In our model of a non-excitable cell, both cAMP and calcium concentrations can oscillate. If mutually inhibitory, cross-talk between the two second messengers can increase the range of agonist concentrations for which oscillations occur. If mutually activating, cross-talk decreases the oscillation range, but can generate 'bursting' oscillations of calcium and may enable better filtering of noise. CONCLUSION: We postulate that this increased dynamical complexity allows the cell to encode more information, particularly if both second messengers encode signals. In their native environments, it is unlikely that cells are exposed to one stimulus at a time, and cross-talk may help generate sufficiently complex responses to allow the cell to discriminate between different combinations and concentrations of extracellular agonists.

  11. A history of stress alters drought calcium signalling pathways in Arabidopsis.

    Science.gov (United States)

    Knight, H; Brandt, S; Knight, M R

    1998-12-01

    Environmental stresses commonly encountered by plants lead to rapid transient elevations in cytosolic free calcium concentration ([Ca2+]cyt) (Bush, 1995; Knight et al., 1991). These cellular calcium (Ca2+) signals lead ultimately to the increased expression of stress-responsive genes, including those encoding proteins of protective function (Knight et al., 1996; Knight et al., 1997). The kinetics and magnitude of the Ca2+ signal, or 'calcium signature', differ between different stimuli and are thought to contribute to the specificity of the end response (Dolmetsch et al., 1997; McAinsh and Hetherington, 1998). We measured [Ca2+]cyt changes during treatment with mannitol (to mimic drought stress) in whole intact seedlings of Arabidopsis thaliana. The responses of plants which were previously exposed to osmotic and oxidative stresses were compared to those of control plants. We show here that osmotic stress-induced Ca2+ responses can be markedly altered by previous encounters with either osmotic or oxidative stress. The nature of the alterations in Ca2+ response depends on the identity and severity of the previous stress: oxidative stress pre-treatment reduced the mannitol-induced [Ca2+]cyt response whereas osmotic stress pretreatment increased the [Ca2+]cyt response. Therefore, our data show that different combinations of environmental stress can produce novel Ca2+ signal outputs. These alterations are accompanied by corresponding changes in the patterns of osmotic stress-induced gene expression and, in the case of osmotic stress pre-treatment, the acquisition of stress-tolerance. This suggests that altered Ca2+ responses encode a 'memory' of previous stress encounters and thus may perhaps be involved in acclimation to environmental stresses. PMID:10069075

  12. G-protein- and cAMP-dependent L-channel gating modulation: a manyfold system to control calcium entry in neurosecretory cells.

    Science.gov (United States)

    Carbone, E; Carabelli, V; Cesetti, T; Baldelli, P; Hernández-Guijo, J M; Giusta, L

    2001-09-01

    Voltage-gated Ca2+ channels are crucial to the control of Ca2+ entry in neurosecretory cells. In the chromaffin cells of adrenal medulla, paracrinally or autocrinally released neurotransmitters induce profound changes in Ca2+ channel gating and Ca2+-dependent events controlling catecholamine secretion and cell activity. The generally held view of these processes is that neurotransmitter-induced modulation of the most widely expressed Ca2+ channels in these cells (N-, P/Q- and L-type) follows two distinct pathways: a direct membrane-delimited Gi/o-protein-induced inhibition of N- and P/Q-type and a remote cAMP-mediated facilitation of L-channels. Both actions depend on voltage, although with remarkably different molecular and kinetic aspects. Recent findings, however, challenge this simple scheme and suggest that L-channels do not require strong pre-pulses to be recruited or facilitated. They are available during normal depolarizations and may be tonically inhibited by Gi/o proteins activated by the released neurotransmitters. Like the N- and P/Q-channels, this autocrine modulation is localized to membrane microareas. Unlike N- and P/Q-channels, however, the inhibition of L-channels is largely independent of voltage and develops in parallel with cAMP-mediated potentiation of channel gating. As L-channels play a crucial role in the control of catecholamine release in chromaffin cells, the two opposite modulations mediated by Gi/o proteins and cAMP may represent an effective way to broaden the dynamic range of Ca2+ signals controlling exocytosis. Here, we review the basic features of this novel L-type channel inhibition comparing it to the well-established forms of L-channel potentiation and voltage-dependent facilitation. PMID:11680611

  13. VSNL1 Co-expression networks in aging include calcium signaling, synaptic plasticity, and Alzheimer’s disease pathways

    Directory of Open Access Journals (Sweden)

    C W Lin

    2015-03-01

    Full Text Available The Visinin-like 1 (VSNL1 gene encodes Visinin-like protein 1, a peripheral biomarker for Alzheimer disease (AD. Little is known, however, about normal VSNL1 expression in brain and the biologic networks in which it participates. Frontal cortex gray matter from 209 subjects without neurodegenerative or psychiatric illness, ranging in age from 16–91, were processed on Affymetrix GeneChip 1.1 ST and Human SNP Array 6.0. VSNL1 expression was unaffected by age and sex, and not significantly associated with SNPs in cis or trans. VSNL1 was significantly co-expressed with genes in pathways for Calcium Signaling, AD, Long Term Potentiation, Long Term Depression, and Trafficking of AMPA Receptors. The association with AD was driven, in part, by correlation with amyloid precursor protein (APP expression. These findings provide an unbiased link between VSNL1 and molecular mechanisms of AD, including pathways implicated in synaptic pathology in AD. Whether APP may drive increased VSNL1 expression, VSNL1 drives increased APP expression, or both are downstream of common pathogenic regulators will need to be evaluated in model systems.

  14. Pathways and Subcellular Compartmentation of NAD Biosynthesis in Human Cells: FROM ENTRY OF EXTRACELLULAR PRECURSORS TO MITOCHONDRIAL NAD GENERATION*

    OpenAIRE

    Nikiforov, Andrey; Dölle, Christian; Niere, Marc; Ziegler, Mathias

    2011-01-01

    NAD is a vital redox carrier, and its degradation is a key element of important regulatory pathways. NAD-mediated functions are compartmentalized and have to be fueled by specific biosynthetic routes. However, little is known about the different pathways, their subcellular distribution, and regulation in human cells. In particular, the route(s) to generate mitochondrial NAD, the largest subcellular pool, is still unknown. To visualize organellar NAD changes in cells, we targeted poly(ADP-ribo...

  15. Conditions and constraints for astrocyte calcium signaling in the hippocampal mossy fiber pathway

    OpenAIRE

    Haustein, Martin D.; Kracun, Sebastian; Lu, Xiao-Hong; Shih, Tiffany; Jackson-Weaver, Olan; Tong, Xiaoping; Xu, Ji; Yang, X William; O'Dell, Thomas J.; Marvin, Jonathan S.; Ellisman, Mark H.; Bushong, Eric A.; Looger, Loren L.; Khakh, Baljit S.

    2014-01-01

    The spatiotemporal activities of astrocyte Ca2+ signaling in mature neuronal circuits remain unclear. We used genetically encoded Ca2+ and glutamate indicators as well as pharmacogenetic and electrical control of neurotransmitter release to explore astrocyte activity in the hippocampal mossy fiber pathway. Our data revealed numerous localised spontaneous Ca2+ signals in astrocyte branches and territories, but these were not driven by neuronal activity or glutamate. Moreover, evoked astrocyte ...

  16. Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.

    Science.gov (United States)

    Arking, Dan E; Pulit, Sara L; Crotti, Lia; van der Harst, Pim; Munroe, Patricia B; Koopmann, Tamara T; Sotoodehnia, Nona; Rossin, Elizabeth J; Morley, Michael; Wang, Xinchen; Johnson, Andrew D; Lundby, Alicia; Gudbjartsson, Daníel F; Noseworthy, Peter A; Eijgelsheim, Mark; Bradford, Yuki; Tarasov, Kirill V; Dörr, Marcus; Müller-Nurasyid, Martina; Lahtinen, Annukka M; Nolte, Ilja M; Smith, Albert Vernon; Bis, Joshua C; Isaacs, Aaron; Newhouse, Stephen J; Evans, Daniel S; Post, Wendy S; Waggott, Daryl; Lyytikäinen, Leo-Pekka; Hicks, Andrew A; Eisele, Lewin; Ellinghaus, David; Hayward, Caroline; Navarro, Pau; Ulivi, Sheila; Tanaka, Toshiko; Tester, David J; Chatel, Stéphanie; Gustafsson, Stefan; Kumari, Meena; Morris, Richard W; Naluai, Åsa T; Padmanabhan, Sandosh; Kluttig, Alexander; Strohmer, Bernhard; Panayiotou, Andrie G; Torres, Maria; Knoflach, Michael; Hubacek, Jaroslav A; Slowikowski, Kamil; Raychaudhuri, Soumya; Kumar, Runjun D; Harris, Tamara B; Launer, Lenore J; Shuldiner, Alan R; Alonso, Alvaro; Bader, Joel S; Ehret, Georg; Huang, Hailiang; Kao, W H Linda; Strait, James B; Macfarlane, Peter W; Brown, Morris; Caulfield, Mark J; Samani, Nilesh J; Kronenberg, Florian; Willeit, Johann; Smith, J Gustav; Greiser, Karin H; Meyer Zu Schwabedissen, Henriette; Werdan, Karl; Carella, Massimo; Zelante, Leopoldo; Heckbert, Susan R; Psaty, Bruce M; Rotter, Jerome I; Kolcic, Ivana; Polašek, Ozren; Wright, Alan F; Griffin, Maura; Daly, Mark J; Arnar, David O; Hólm, Hilma; Thorsteinsdottir, Unnur; Denny, Joshua C; Roden, Dan M; Zuvich, Rebecca L; Emilsson, Valur; Plump, Andrew S; Larson, Martin G; O'Donnell, Christopher J; Yin, Xiaoyan; Bobbo, Marco; D'Adamo, Adamo P; Iorio, Annamaria; Sinagra, Gianfranco; Carracedo, Angel; Cummings, Steven R; Nalls, Michael A; Jula, Antti; Kontula, Kimmo K; Marjamaa, Annukka; Oikarinen, Lasse; Perola, Markus; Porthan, Kimmo; Erbel, Raimund; Hoffmann, Per; Jöckel, Karl-Heinz; Kälsch, Hagen; Nöthen, Markus M; den Hoed, Marcel; Loos, Ruth J F; Thelle, Dag S; Gieger, Christian; Meitinger, Thomas; Perz, Siegfried; Peters, Annette; Prucha, Hanna; Sinner, Moritz F; Waldenberger, Melanie; de Boer, Rudolf A; Franke, Lude; van der Vleuten, Pieter A; Beckmann, Britt Maria; Martens, Eimo; Bardai, Abdennasser; Hofman, Nynke; Wilde, Arthur A M; Behr, Elijah R; Dalageorgou, Chrysoula; Giudicessi, John R; Medeiros-Domingo, Argelia; Barc, Julien; Kyndt, Florence; Probst, Vincent; Ghidoni, Alice; Insolia, Roberto; Hamilton, Robert M; Scherer, Stephen W; Brandimarto, Jeffrey; Margulies, Kenneth; Moravec, Christine E; del Greco M, Fabiola; Fuchsberger, Christian; O'Connell, Jeffrey R; Lee, Wai K; Watt, Graham C M; Campbell, Harry; Wild, Sarah H; El Mokhtari, Nour E; Frey, Norbert; Asselbergs, Folkert W; Mateo Leach, Irene; Navis, Gerjan; van den Berg, Maarten P; van Veldhuisen, Dirk J; Kellis, Manolis; Krijthe, Bouwe P; Franco, Oscar H; Hofman, Albert; Kors, Jan A; Uitterlinden, André G; Witteman, Jacqueline C M; Kedenko, Lyudmyla; Lamina, Claudia; Oostra, Ben A; Abecasis, Gonçalo R; Lakatta, Edward G; Mulas, Antonella; Orrú, Marco; Schlessinger, David; Uda, Manuela; Markus, Marcello R P; Völker, Uwe; Snieder, Harold; Spector, Timothy D; Ärnlöv, Johan; Lind, Lars; Sundström, Johan; Syvänen, Ann-Christine; Kivimaki, Mika; Kähönen, Mika; Mononen, Nina; Raitakari, Olli T; Viikari, Jorma S; Adamkova, Vera; Kiechl, Stefan; Brion, Maria; Nicolaides, Andrew N; Paulweber, Bernhard; Haerting, Johannes; Dominiczak, Anna F; Nyberg, Fredrik; Whincup, Peter H; Hingorani, Aroon D; Schott, Jean-Jacques; Bezzina, Connie R; Ingelsson, Erik; Ferrucci, Luigi; Gasparini, Paolo; Wilson, James F; Rudan, Igor; Franke, Andre; Mühleisen, Thomas W; Pramstaller, Peter P; Lehtimäki, Terho J; Paterson, Andrew D; Parsa, Afshin; Liu, Yongmei; van Duijn, Cornelia M; Siscovick, David S; Gudnason, Vilmundur; Jamshidi, Yalda; Salomaa, Veikko; Felix, Stephan B; Sanna, Serena; Ritchie, Marylyn D; Stricker, Bruno H; Stefansson, Kari; Boyer, Laurie A; Cappola, Thomas P; Olsen, Jesper V; Lage, Kasper; Schwartz, Peter J; Kääb, Stefan; Chakravarti, Aravinda; Ackerman, Michael J; Pfeufer, Arne; de Bakker, Paul I W; Newton-Cheh, Christopher

    2014-08-01

    The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD. PMID:24952745

  17. Odontogenic differentiation of human dental pulp cells by calcium silicate materials stimulating via FGFR/ERK signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Chao-Hsin [School of Dentistry, Chung Shan Medical University, Taichung City, Taiwan (China); Hung, Chi-Jr; Huang, Tsui-Hsien [School of Dentistry, Chung Shan Medical University, Taichung City, Taiwan (China); Department of Dentistry, Chung Shan Medical University Hospital, Taichung City, Taiwan (China); Lin, Chi-Chang [Department of Chemical and Materials Engineering, Tunghai University, Taichung City, Taiwan (China); Kao, Chia-Tze [School of Dentistry, Chung Shan Medical University, Taichung City, Taiwan (China); Department of Dentistry, Chung Shan Medical University Hospital, Taichung City, Taiwan (China); Shie, Ming-You, E-mail: eviltacasi@gmail.com [Department of Chemical and Materials Engineering, Tunghai University, Taichung City, Taiwan (China)

    2014-10-01

    Bone healing needs a complex interaction of growth factors that establishes an environment for efficient bone formation. We examine how calcium silicate (CS) and tricalcium phosphate (β-TCP) cements influence the behavior of human dental pulp cells (hDPCs) through fibroblast growth factor receptor (FGFR) and active MAPK pathways, in particular ERK. The hDPCs are cultured with β-TCP and CS, after which the cells' viability and odontogenic differentiation markers are determined by using PrestoBlue® assay and western blot, respectively. The effect of small interfering RNA (siRNA) transfection targeting FGFR was also evaluated. The results showed that CS promoted cell proliferation and enhances FGFR expression. It was also found that CS increases ERK and p38 activity in hDPCs, and furthermore, raises the expression and secretion of DSP, and DMP-1. Additionally, statistically significant differences (p < 0.05) have been found in the calcium deposition in si-FGFR transfection and ERK inhibitor between CS and β-TCP; these variations indicated that ERK/MAPK signaling is involved in the silicon-induced odontogenic differentiation of hDPCs. The current study shows that CS substrates play a key role in odontoblastic differentiation of hDPCs through FGFR and modulate ERK/MAPK activation. - Highlights: • CS influences the behavior of hDPCs through fibroblast growth factor receptor. • CS increases ERK and p38 activity in hDPCs. • ERK/MAPK signaling is involved in the Si-induced odontogenic differentiation of hDPCs. • Ca staining shows that FGFR regulates hDPC differentiation on CS, but not on β-TCP.

  18. Odontogenic differentiation of human dental pulp cells by calcium silicate materials stimulating via FGFR/ERK signaling pathway

    International Nuclear Information System (INIS)

    Bone healing needs a complex interaction of growth factors that establishes an environment for efficient bone formation. We examine how calcium silicate (CS) and tricalcium phosphate (β-TCP) cements influence the behavior of human dental pulp cells (hDPCs) through fibroblast growth factor receptor (FGFR) and active MAPK pathways, in particular ERK. The hDPCs are cultured with β-TCP and CS, after which the cells' viability and odontogenic differentiation markers are determined by using PrestoBlue® assay and western blot, respectively. The effect of small interfering RNA (siRNA) transfection targeting FGFR was also evaluated. The results showed that CS promoted cell proliferation and enhances FGFR expression. It was also found that CS increases ERK and p38 activity in hDPCs, and furthermore, raises the expression and secretion of DSP, and DMP-1. Additionally, statistically significant differences (p < 0.05) have been found in the calcium deposition in si-FGFR transfection and ERK inhibitor between CS and β-TCP; these variations indicated that ERK/MAPK signaling is involved in the silicon-induced odontogenic differentiation of hDPCs. The current study shows that CS substrates play a key role in odontoblastic differentiation of hDPCs through FGFR and modulate ERK/MAPK activation. - Highlights: • CS influences the behavior of hDPCs through fibroblast growth factor receptor. • CS increases ERK and p38 activity in hDPCs. • ERK/MAPK signaling is involved in the Si-induced odontogenic differentiation of hDPCs. • Ca staining shows that FGFR regulates hDPC differentiation on CS, but not on β-TCP

  19. Stimulation of Odontogenesis and Angiogenesis via Bioactive Nanocomposite Calcium Phosphate Cements Through Integrin and VEGF Signaling Pathways.

    Science.gov (United States)

    Lee, Sang-Im; Lee, Eui-Suk; El-Fiqi, Ahmed; Lee, So-Youn; Eun-Cheol Kim; Kim, Hae-Won

    2016-05-01

    Formulating self-setting calcium phosphate cements (CPCs) with secondary phases particularly in the nanoscale order holds great promise to improve biological properties. Here, we focus on the effect that bioactive glass nanoparticles (BGN) incorporated in CPC compositions can have on the proliferation, odontogenic differentiation, and angiogenic stimulation of stem cells derived from human dental pulp (HDPSCs). These odontogenic and angiogenic events are of special importance in the dentin-pulp regeneration processes. In comparison to pure CPCs, nanocomposite cements exhibit a significantly improved proliferation of HDPSCs, and the improvement is more significant as the BGN content increases. The nanocomposite cements substantially enhance the adhesion of cells, and significantly up-regulate odontogenic differentiation, including alkaline phosphatase (ALP) activity and the expressions of odontogenic genes (sialophosphoprotein, dentin matrix protein I, ALP, osteopontin and osteocalcin). Furthermore, the use of nanocomposite cements result in stimulation of angiogenic gene expression (VEGF, FGF-2, VEGFRs, PECAM-1, and VE-cadherin) and protein production (VEGF, VEGFR-1). The angiogenic stimulation by the HDPSCs significantly affects the endothelial cell behaviors, that is, the endothelial cell migration and the tubular network formation are substantially improved when treated with HDPSC-conditioned medium, particularly with the help of nanocomposite cements. The integrin and VEGF signaling pathways are reasoned for the stimulation of the odontogenesis and angiogenesis of cells, where the nanocomposite cements up-regulate the integrin subsets α1, α2, α3, and β1, and activate the integrin downstream signal pathways, such as p-FAK, p-Akt, p-paxillin, JNK, EK, and NF-κB, as well as other nuclear transcriptional factors, including CREB, STAT-3, and ELK-1. The current results indicate that the new formulation of the nanocomposite self-setting cements might provide some

  20. The genetic background affects the vascular response in T-type calcium channels 3.2 deficient mice

    DEFF Research Database (Denmark)

    Svenningsen, Per; Hansen, Pernille B L

    2016-01-01

    -type channels are the dominant Ca(2+) entry pathway in vascular smooth muscle cells, however, T-type calcium channels are also expressed in the cardiovascular system where they play a functional role in the regulation of both contraction and vasodilation in (Chen et al. 2003; Hansen et al. 2001). This article......Voltage-gated calcium channels (Cav ) are important regulators of vascular tone and are attractive targets for pharmacological treatment of hypertension. The clinical used calcium blockers are often not selective for one channel but affect several types of calcium channels (Hansen 2015). L...

  1. Effect of calcium entry blockers on blood pressure and vasoconstrictor responses to alpha-1 adrenoceptor stimulation in conscious spontaneously hypertensive rats

    International Nuclear Information System (INIS)

    In order to investigate whether vascular alpha-1 adrenoceptor antagonism plays a role in the antihypertensive effect of verapamil, tiapamil, and nifedipine, we studied their potencies to inhibit K(+)-induced 45Ca2+ influx in rat isolated aorta and [3H]prazosin binding in rat brain membranes in vitro as well as their antihypertensive effect and functional alpha-1 adrenoceptor blockade in conscious spontaneously hypertensive rats (SHR) in vivo. Tiapamil proved 70 times less potent than verapamil in inhibiting calcium influx, but was equipotent in displacing [3H]prazosin. Nifedipine proved 10 times more potent than verapamil as calcium channel blocker but displayed negligible affinity for alpha-1 adrenoceptors in vitro. In conscious SHR, the three calcium channel blockers dose-dependently reduced mean arterial pressure after oral administration. Only at maximal anti-hypertensive doses, the increases in diastolic pressure to intravenous injection of the selective alpha-1 adrenoceptor agonist cirazoline were temporarily suppressed by nifedipine, verapamil, and tiapamil. No relationship existed between the relative potencies as calcium channel blocker and affinities for alpha-1 adrenoceptor binding sites in vitro with functional vascular alpha-1 adrenoceptor blockade in vivo. The data do not support the hypothesis that vascular alpha-1 adrenoceptor blockade plays a significant role in the anti-hypertensive effect of verapamil and related calcium channel blockers

  2. Ginsenoside Rb1 Attenuates Agonist-Induced Contractile Response via Inhibition of Store-Operated Calcium Entry in Pulmonary Arteries of Normal and Pulmonary Hypertensive Rats

    Directory of Open Access Journals (Sweden)

    Rui-Xing Wang

    2015-03-01

    Full Text Available Background: Pulmonary hypertension (PH is characterized by sustained vasoconstriction, enhanced vasoreactivity and vascular remodeling, which leads to right heart failure and death. Despite several treatments are available, many forms of PH are still incurable. Ginsenoside Rb1, a principle active ingredient of Panax ginseng, exhibits multiple pharmacological effects on cardiovascular system, and suppresses monocrotaline (MCT-induced right heart hypertrophy. However, its effect on the pulmonary vascular functions related to PH is unknown. Methods: We examined the vasorelaxing effects of ginsenoside Rb1 on endothelin-1 (ET-1 induced contraction of pulmonary arteries (PAs and store-operated Ca2+ entry (SOCE in pulmonary arterial smooth muscle cells (PASMCs from chronic hypoxia (CH and MCT-induced PH. Results: Ginsenoside Rb1 elicited concentration-dependent relaxation of ET-1-induced PA contraction. The vasorelaxing effect was unaffected by nifedipine, but abolished by the SOCE blocker Gd3+. Ginsenoside Rb1 suppressed cyclopiazonic acid (CPA-induced PA contraction, and CPA-activated cation entry and Ca2+ transient in PASMCs. ET-1 and CPA-induced contraction, and CPA-activated cation entry and Ca2+ transients were enhanced in PA and PASMCs of CH and MCT-treated rats; the enhanced responses were abolished by ginsenoside Rb1. Conclusion: Ginsenoside Rb1 attenuates ET-1-induced contractile response via inhibition of SOCE, and it can effectively antagonize the enhanced pulmonary vasoreactivity in PH.

  3. Calcium binding protein-mediated regulation of voltage-gated calcium channels linked to human diseases

    Institute of Scientific and Technical Information of China (English)

    Nasrin NFJATBAKHSH; Zhong-ping FENG

    2011-01-01

    Calcium ion entry through voltage-gated calcium channels is essential for cellular signalling in a wide variety of cells and multiple physiological processes. Perturbations of voltage-gated calcium channel function can lead to pathophysiological consequences. Calcium binding proteins serve as calcium sensors and regulate the calcium channel properties via feedback mechanisms. This review highlights the current evidences of calcium binding protein-mediated channel regulation in human diseases.

  4. A nonsense mutation of Stim1 identified in stroke-prone spontaneously hypertensive rats decreased the store-operated calcium entry in astrocytes.

    Science.gov (United States)

    Ohara, Hiroki; Nabika, Toru

    2016-08-01

    We previously identified a nonsense mutation in the stromal interaction molecule-1 (Stim1) resulting in expression of a truncated STIM1 in the stroke-prone spontaneously hypertensive rat (SHRSP). In this study, we evaluated activity of the store-operated Ca(2+)-entry (SOCE) regulated by STIM1 to clarify putative functional abnormalities of the truncated STIM1. As a result, reduced SOCE activity resulting in suppression of cyclooxygenase-2 expression induced by SOCE was found in cultured astrocytes with the truncated STIM1 when compared with those with the wild-type. Our results indicated that the truncated STIM1 impaired Ca(2+) signaling regulated by SOCE and that the impaired SOCE activity might be responsible for pathological phenotypes in SHRSP. PMID:27237974

  5. Calmodulin activation by calcium transients in the postsynaptic density of dendritic spines.

    Directory of Open Access Journals (Sweden)

    Daniel X Keller

    Full Text Available The entry of calcium into dendritic spines can trigger a sequence of biochemical reactions that begins with the activation of calmodulin (CaM and ends with long-term changes to synaptic strengths. The degree of activation of CaM can depend on highly local elevations in the concentration of calcium and the duration of transient increases in calcium concentration. Accurate measurement of these local changes in calcium is difficult because the spaces are so small and the numbers of molecules are so low. We have therefore developed a Monte Carlo model of intracellular calcium dynamics within the spine that included calcium binding proteins, calcium transporters and ion channels activated by voltage and glutamate binding. The model reproduced optical recordings using calcium indicator dyes and showed that without the dye the free intracellular calcium concentration transient was much higher than predicted from the fluorescent signal. Excitatory postsynaptic potentials induced large, long-lasting calcium gradients across the postsynaptic density, which activated CaM. When glutamate was released at the synapse 10 ms before an action potential occurred, simulating activity patterns that strengthen hippocampal synapses, the calcium gradient and activation of CaM in the postsynaptic density were much greater than when the order was reversed, a condition that decreases synaptic strengths, suggesting a possible mechanism underlying the induction of long-term changes in synaptic strength. The spatial and temporal mechanisms for selectivity in CaM activation demonstrated here could be used in other signaling pathways.

  6. Characterization of branchial transepithelial calcium fluxes in freshwater trout, Salmo gairdneri

    International Nuclear Information System (INIS)

    Experiments were performed to determine whether gill transepithelial calcium fluxes in the freshwater trout (Salmo gairdneri) are passive or require active transport and to characterize the mechanism involved. A comparison of the in vivo unidirectional flux ratios with the flux ratios calculated according to the transepithelial electrochemical gradients revealed that calcium uptake from the water requires active transport of Ca2+. The inhibition of calcium uptake by external lanthanum, the specific deposition of lanthanum on the apical surface of chloride cells, and the favorable electrochemical gradient for calcium across the apical membrane suggest that the initial step in branchial calcium uptake is the passive entry of calcium into the cytosol of chloride cells through apical channels that are permeable to calcium. The study of gill basolateral plasma membrane vesicles demonstrated the existence of a high-affinity calmodulin-dependent calcium-transporting system. This system actively transports calcium from the cytosol of chloride cells into the plasma against a sizeable electrochemical gradient, thereby completing the transepithelial uptake of calcium. Calcium efflux occurs passively through paracellular pathways between chloride cells and adjacent pavement cells or between neighboring pavement cells

  7. The secretory pathway calcium ATPase PMR-1/SPCA1 has essential roles in cell migration during Caenorhabditis elegans embryonic development.

    Directory of Open Access Journals (Sweden)

    Vida Praitis

    2013-05-01

    Full Text Available Maintaining levels of calcium in the cytosol is important for many cellular events, including cell migration, where localized regions of high calcium are required to regulate cytoskeletal dynamics, contractility, and adhesion. Studies show inositol-trisphosphate receptors (IP3R and ryanodine receptors (RyR, which release calcium into the cytosol, are important regulators of cell migration. Similarly, proteins that return calcium to secretory stores are likely to be important for cell migration. The secretory protein calcium ATPase (SPCA is a Golgi-localized protein that transports calcium from the cytosol into secretory stores. SPCA has established roles in protein processing, metal homeostasis, and inositol-trisphosphate signaling. Defects in the human SPCA1/ATP2C1 gene cause Hailey-Hailey disease (MIM# 169600, a genodermatosis characterized by cutaneous blisters and fissures as well as keratinocyte cell adhesion defects. We have determined that PMR-1, the Caenorhabditis elegans ortholog of SPCA1, plays an essential role in embryogenesis. Pmr-1 strains isolated from genetic screens show terminal phenotypes, such as ventral and anterior enclosure failures, body morphogenesis defects, and an unattached pharynx, which are caused by earlier defects during gastrulation. In Pmr-1 embryos, migration rates are significantly reduced for cells moving along the embryo surface, such as ventral neuroblasts, C-derived, and anterior-most blastomeres. Gene interaction experiments show changing the activity of itr-1/IP3R and unc-68/RyR modulates levels of embryonic lethality in Pmr-1 strains, indicating pmr-1 acts with these calcium channels to regulate cell migration. This analysis reveals novel genes involved in C. elegans cell migration, as well as a new role in cell migration for the highly conserved SPCA gene family.

  8. Anti-tumor Necrosis Factor Alpha (Infliximab) Attenuates Apoptosis, Oxidative Stress, and Calcium Ion Entry Through Modulation of Cation Channels in Neutrophils of Patients with Ankylosing Spondylitis.

    Science.gov (United States)

    Ugan, Yunus; Nazıroğlu, Mustafa; Şahin, Mehmet; Aykur, Mehmet

    2016-08-01

    Ankylosing Spondylitis (AS) is known to be associated with increased neutrophil activation and oxidative stress, however, the mechanism of neutrophil activation is still unclear. We have hypothesized that the antioxidant and anti-tumor necrosis factor properties of infliximab may affect intracellular Ca(2+) concentration in the neutrophils of AS patients. The objective of this study was to investigate the effects of infliximab on calcium signaling, oxidative stress, and apoptosis in neutrophils of AS patients. Neutrophils collected from ten patients with AS and ten healthy controls were used in the study. In a cell viability test, the ideal non-toxic dose and incubation time of infliximab were found as 100 μM and 1 h, respectively. In some experiments, the neutrophils were incubated with the voltage-gated calcium channel (VGCC) blockers verapamil + diltiazem (V + D) and the TRPM2 channel blocker 2-aminoethyl diphenylborinate (2-APB). Intracellular Ca(2+) concentration, lipid peroxidation, apoptosis, caspase 3, and caspase 9 values were high in neutrophils of AS patients and were reduced with infliximab treatment. Reduced glutathione level and glutathione peroxidase activity were low in the patients and increased with infliximab treatment. The intracellular Ca(2+) concentrations were low in 2-APB and V + D groups. In conclusion, the current study suggests that infliximab is useful against apoptotic cell death and oxidative stress in neutrophils of patients with AS, which seem to be dependent on increased levels of intracellular Ca(2+) through activation of TRPM2 and VGCC. PMID:26956056

  9. Calcium signaling and T-type calcium channels in cancer cell cycling

    Institute of Scientific and Technical Information of China (English)

    James T Taylor; Xiang-Bin Zeng; Jonathan E Pottle; Kevin Lee; Alun R Wang; Stephenie G Yi; Jennifer A S Scruggs; Suresh S Sikka; Ming Li

    2008-01-01

    Regulation of intracellular calcium is an important signaling mechanism for cell proliferation in both normal and cancerous cells. In normal epithelial cells,free calcium concentration is essential for cells to enter and accomplish the S phase and the M phase of the cell cycle. In contrast, cancerous cells can pass these phases of the cell cycle with much lower cytoplasmic free calcium concentrations, indicating an alternative mechanism has developed for fulfilling the intracellular calcium requirement for an increased rate of DNA synthesis and mitosis of fast replicating cancerous cells. The detailed mechanism underlying the altered calcium loading pathway remains unclear;however, there is a growing body of evidence that suggests the T-type Ca2+ channel is abnormally expressed in cancerous cells and that blockade of these channels may reduce cell proliferation in addition to inducing apoptosis. Recent studies also show that the expression of T-type Ca2+ channels in breast cancer cells is proliferation state dependent, i.e. the channels are expressed at higher levels during the fast-replication period, and once the cells are in a non-proliferation state, expression of this channel isminimal. Therefore, selectively blocking calcium entry into cancerous cells may be a valuable approach for preventing tumor growth. Since T-type Ca2+ channels are not expressed in epithelial cells, selective T-type Ca2+ channel blockers may be useful in the treatment of certain types of cancers.

  10. Antinociceptive Effect of Vardenafil on Carrageenan-Induced Hyperalgesia in Rat: involvement of Nitric Oxide/Cyclic Guanosine Monophosphate/Calcium Channels Pathway.

    Science.gov (United States)

    Gediz, Ezgi İkiz; Nacitarhan, Cahit; Minareci, Edibe; Sadan, Gulay

    2015-01-01

    In this study, we aimed to investigate the peripheral antinociception effects of specific phosphodiesterase 5 (PDE-5) inhibitor vardenafil on carrageenan-induced nociception in rats, and the role of calcium besides the L-arginine- nitric oxide (NO)- cyclic guanosine monophophate (cGMP) pathway in these effects. Hyperalgesia was induced by the intraplantar injection of 0.1 mL fresh carrageenan solution to right hind-paw whereas, saline as a vehicle of carrageenan was injected to the left paw. This procedure was used for measuring mechanic nociception pressure via an analgesimeter. Pressure which produced nociception was measured before (0 minute) and after(15, 30, 60 and 120 minutes) carrageenan injection. Local administration of vardenafil produced a dose-dependent antinociceptive effect. Pretreatment with N(W)-nitro-L-arginine methyl ester (L-NAME, nitric oxide synthase inhibitor), oxadiazolo (4, 3, a) quinoxalin -1-one (ODQ, inhibitor of guanylyl cyclase) or A23187 (calcium ionophore) decreased the effect of vardenafil. In contrast, L-arginine (nitric oxide donor) seemed to potentiate the vardenafil-induced antinociception. Our results suggest that phosphodiesterase type-5 inhibitor vardenafil may offer a new therapeutic tool to treat pain. It's effect was probably result from L-arginine/NO-cGMP pathway activation and Ca + 2 channels are also involved. PMID:26664380

  11. Adenosine A{sub 2A} receptor-dependent proliferation of pulmonary endothelial cells is mediated through calcium mobilization, PI3-kinase and ERK1/2 pathways

    Energy Technology Data Exchange (ETDEWEB)

    Ahmad, Aftab, E-mail: Aftab.Ahmad@UCDenver.edu [Pediatric Airway Research Center, Department of Pediatrics, Aurora, CO (United States); Schaack, Jerome B. [Department of Microbiology, University of Colorado Denver, Aurora, CO (United States); White, Carl W.; Ahmad, Shama [Pediatric Airway Research Center, Department of Pediatrics, Aurora, CO (United States)

    2013-05-10

    Highlights: •A{sub 2A} receptor-induced pulmonary endothelial growth is mediated by PI3K and ERK1/2. •Cytosolic calcium mobilization is also critical for pulmonary endothelial growth. •Effectors of A{sub 2A} receptor, like tyrosine kinases and cAMP increase PI3K/Akt signaling. •Activation of A{sub 2A} receptor can contribute to vascular remodeling. -- Abstract: Hypoxia and HIF-2α-dependent A{sub 2A} receptor expression and activation increase proliferation of human lung microvascular endothelial cells (HLMVECs). This study was undertaken to investigate the signaling mechanisms that mediate the proliferative effects of A{sub 2A} receptor. A{sub 2A} receptor-mediated proliferation of HLMVECs was inhibited by intracellular calcium chelation, and by specific inhibitors of ERK1/2 and PI3-kinase (PI3K). The adenosine A{sub 2A} receptor agonist CGS21680 caused intracellular calcium mobilization in controls and, to a greater extent, in A{sub 2A} receptor-overexpressing HLMVECs. Adenoviral-mediated A{sub 2A} receptor overexpression as well as receptor activation by CGS21680 caused increased PI3K activity and Akt phosphorylation. Cells overexpressing A{sub 2A} receptor also manifested enhanced ERK1/2 phosphorylation upon CGS21680 treatment. A{sub 2A} receptor activation also caused enhanced cAMP production. Likewise, treatment with 8Br-cAMP increased PI3K activity. Hence A{sub 2A} receptor-mediated cAMP production and PI3K and Akt phosphorylation are potential mediators of the A{sub 2A}-mediated proliferative response of HLMVECs. Cytosolic calcium mobilization and ERK1/2 phosphorylation are other critical effectors of HLMVEC proliferation and growth. These studies underscore the importance of adenosine A{sub 2A} receptor in activation of survival and proliferative pathways in pulmonary endothelial cells that are mediated through PI3K/Akt and ERK1/2 pathways.

  12. Effects of ethanol on calcium transport across the liver cell plasma membrane

    International Nuclear Information System (INIS)

    The effect of ethanol on calcium transport by the liver cell was studied by using a rat liver slice preparation. Ethanol was shown to decrease by about 30% the rate constant for 45Ca efflux from the intracellular compartment. This inhibitory effect of ethanol was not observed in the absence of Ca2+ or Na+ from the incubation medium. Ethanol was also shown to greatly increase non-insulin calcium uptake by liver slices. This effect of ethanol appeared to be dose dependent and was not observed in the absence of Na+ from the incubation medium. The ability of ethanol to increase calcium uptake by the hepatocyte was completely blocked by 1 mM Amiloride. Amiloride, however, did not affect the increased entry of either Na+ or Ca2+ produced by 10 mM Ouabain, a specific inhibitor of the sodium pump. Carbon tetrachloride (CCl4), a well known hepatotoxin, also increased calcium uptake by the hepatocyte. Amiloride, however, was not able to block the CCl4-induced calcium uptake. These results suggest that ethanol activates a Na+ entry pathway, probably represented by a Na+/H+ exchanger, which in turn stimulates an entry of Ca2+ through a Na+/Ca2+ exchange mechanism located in the plasma membrane of the hepatocyte

  13. 17β-estradiol rapidly activates calcium release from intracellular stores via the GPR30 pathway and MAPK phosphorylation in osteocyte-like MLO-Y4 cells

    KAUST Repository

    Ren, Jian

    2012-03-06

    Estrogen regulates critical cellular functions, and its deficiency initiates bone turnover and the development of bone mass loss in menopausal females. Recent studies have demonstrated that 17β-estradiol (E 2) induces rapid non-genomic responses that activate downstream signaling molecules, thus providing a new perspective to understand the relationship between estrogen and bone metabolism. In this study, we investigated rapid estrogen responses, including calcium release and MAPK phosphorylation, in osteocyte-like MLO-Y4 cells. E 2 elevated [Ca 2+] i and increased Ca 2+ oscillation frequency in a dose-dependent manner. Immunolabeling confirmed the expression of three estrogen receptors (ERα, ERβ, and G protein-coupled receptor 30 [GPR30]) in MLO-Y4 cells and localized GPR30 predominantly to the plasma membrane. E 2 mobilized calcium from intracellular stores, and the use of selective agonist(s) for each ER showed that this was mediated mainly through the GPR30 pathway. MAPK phosphorylation increased in a biphasic manner, with peaks occurring after 7 and 60 min. GPR30 and classical ERs showed different temporal effects on MAPK phosphorylation and contributed to MAPK phosphorylation sequentially. ICI182,780 inhibited E 2 activation of MAPK at 7 min, while the GPR30 agonist G-1 and antagonist G-15 failed to affect MAPK phosphorylation levels. G-1-mediated MAPK phosphorylation at 60 min was prevented by prior depletion of calcium stores. Our data suggest that E 2 induces the non-genomic responses Ca 2+ release and MAPK phosphorylation to regulate osteocyte function and indicate that multiple receptors mediate rapid E 2 responses. © 2012 Springer Science+Business Media, LLC.

  14. 17β-estradiol rapidly activates calcium release from intracellular stores via the GPR30 pathway and MAPK phosphorylation in osteocyte-like MLO-Y4 cells.

    Science.gov (United States)

    Ren, Jian; Wu, Jun Hua

    2012-05-01

    Estrogen regulates critical cellular functions, and its deficiency initiates bone turnover and the development of bone mass loss in menopausal females. Recent studies have demonstrated that 17β-estradiol (E(2)) induces rapid non-genomic responses that activate downstream signaling molecules, thus providing a new perspective to understand the relationship between estrogen and bone metabolism. In this study, we investigated rapid estrogen responses, including calcium release and MAPK phosphorylation, in osteocyte-like MLO-Y4 cells. E(2) elevated [Ca(2+)]( i ) and increased Ca(2+) oscillation frequency in a dose-dependent manner. Immunolabeling confirmed the expression of three estrogen receptors (ERα, ERβ, and G protein-coupled receptor 30 [GPR30]) in MLO-Y4 cells and localized GPR30 predominantly to the plasma membrane. E(2) mobilized calcium from intracellular stores, and the use of selective agonist(s) for each ER showed that this was mediated mainly through the GPR30 pathway. MAPK phosphorylation increased in a biphasic manner, with peaks occurring after 7 and 60 min. GPR30 and classical ERs showed different temporal effects on MAPK phosphorylation and contributed to MAPK phosphorylation sequentially. ICI182,780 inhibited E(2) activation of MAPK at 7 min, while the GPR30 agonist G-1 and antagonist G-15 failed to affect MAPK phosphorylation levels. G-1-mediated MAPK phosphorylation at 60 min was prevented by prior depletion of calcium stores. Our data suggest that E(2) induces the non-genomic responses Ca(2+) release and MAPK phosphorylation to regulate osteocyte function and indicate that multiple receptors mediate rapid E(2) responses. PMID:22392527

  15. Relation between muscarinic receptor cationic current and internal calcium in guinea-pig jejunal smooth muscle cells.

    Science.gov (United States)

    Pacaud, P; Bolton, T B

    1991-09-01

    1. The action of carbachol, which activates muscarinic receptors, was studied in single patch-clamped cells where free internal calcium concentration in the cell (Cai2+) was estimated using the emission from the dye Indo-1. Cells were dialysed with potassium-free caesium solution to block any Ca(2+)-activated K(+)-current. 2. Carbachol applied to the cell evoked an initial peak in Cai2+ followed by a smaller sustained rise (plateau) upon which several oscillations in Cai2+ were often superimposed; the changes in inward, cationic current (icarb) followed changes in Cai2+ closely. Calcium entry blocker did not affect these responses. 3. The initial peak in Cai2+ produced by carbachol was due to calcium store release: it was essentially unchanged at +50 mV, and abolished by prior application of caffeine (10 mM) to the cell or by inclusion of heparin (which blocks D-myoinositol 1,4,5-trisphosphate receptors) in the pipette. In contrast, the rise in Cai2+ produced by ATP in rabbit ear artery smooth muscle cells was unaffected by caffeine or heparin as it was due to calcium entry into the cell. 4. The later sustained rise (plateau) in Cai2+ produced by carbachol was due to the entry of calcium into the cell down its electrochemical gradient as it was affected by changing the cell membrane potential or the calcium concentration of the bathing solution. As the sustained rise in Cai2+ produced by caffeine had similar properties, it was suggested that depletion of calcium stores can evoke an increased calcium entry into the cell through some pathway. 5. The cationic current evoked by carbachol was strongly dependent on Cai2+. It was small if any rise in Cai2+ due to calcium store release was prevented by the inclusion of heparin in the pipette solution and increased greatly if calcium entry was provoked through voltage-dependent channels by applying a depolarizing pulse or if calcium was released from stores by caffeine. 6. In the longitudinal muscle of guinea-pig small

  16. Calcium Dysregulation Induces Apoptosis-inducing Factor Release: Cross-talk Between PARP-1- and Calpain- Signaling Pathways

    OpenAIRE

    Vosler, Peter S.; Sun, Dandan; Wang, Suping; Gao, Yanqin; Kintner, Douglas B.; Signore, Armando P.; Cao, Guodong; Chen, Jun

    2009-01-01

    Recent discoveries show that caspase-independent cell death pathways are a pervasive mechanism in neurodegenerative diseases, and apoptosis-inducing factor (AIF) is an important effector of this mode of neuronal death. There are currently two known mechanisms underlying AIF release following excitotoxic stress, PARP-1 and calpain. To test whether there is an interaction between PARP-1 and calpain in triggering AIF release, we used the NMDA toxicity model in rat primary cortical neurons. Expos...

  17. Store-operated calcium channels and pro-inflammatory signals

    Institute of Scientific and Technical Information of China (English)

    Wei-chiao CHANG

    2006-01-01

    In non-excitable cells such as T lymphocytes,hepatocytes,mast cells,endothelia and epithelia,the major pathway for calcium(Ca2+)entry is through store-operated Ca2+ channels in the plasma membrane.These channels are activated by the emptying of intracellular Ca2+ stores,however,neither the gating mechanism nor the downstream targets of these channels has been clear established.Here,I review some of the proposed gating mechanisms of store-operated Ca2+ channels and the functional implications in regulating pro-inflammatory signals.

  18. Calcium-Sensing Receptor in Human Peripheral Blood T Lymphocytes Is Involved in the AMI Onset and Progression through the NF-κB Signaling Pathway.

    Science.gov (United States)

    Zeng, Jing-Ya; Du, Jing-Jing; Pan, Ying; Wu, Jian; Bi, Hai-Liang; Cui, Bao-Hong; Zhai, Tai-Yu; Sun, Yong; Sun, Yi-Hua

    2016-01-01

    Acute myocardial infarction (AMI) is a condition triggered by an inflammatory process that seriously affects human health. Calcium-sensing receptor (CaSR) in T lymphocytes is involved during the inflammation reaction. However, the relationship between them is not very clear. In this study, we collected human peripheral blood T lymphocytes from patients with AMI and in different stages of percutaneous coronary intervention (PCI) (at the onset of AMI, the first day after PCI (PCI-1), PCI-3, and PCI-5) to study the CaSR and NF-κB pathway protein expression, cytokine release and T cell apoptosis. The results showed that the expressions of CaSR, P-p65, Caspase-12, and the secretions of Th-1 and Th-2 type cytokines were increased at the onset of AMI, especially on the PCI-1. Meanwhile, the apoptosis rate of CD(3+), CD(4+) and CD(8+) T lymphocytes also increased. However, from PCI-3, all the indicators began to decline. In addition, we also found that positive CaSR small interfering RNA (siRNA) transfection in T lymphocytes and NF-κB pathway blocker Bay-11-7082 reversed the increased expressions of CaSR, P-p65, Caspase-12, reduced the secretions of Th-1 and Th-2 type cytokines, and decreased T lymphocytes apoptosis rate not only in the AMI patients but also in the normal controls. All of these results indicated that CaSR in the human peripheral blood T lymphocytes were involved in the AMI onset and progression, which probably was related to the NF-κB pathway. Our study demonstrated the relationship between AMI and CaSR, and will provide new effective prevention theory and new targets for drug treatment. PMID:27563892

  19. Mitochondrial response and calcium ion change in apoptotic insect cells induced by SfaMNPV

    Institute of Scientific and Technical Information of China (English)

    XIU Meihong; PENG Jianxin; HONG Huazhu

    2005-01-01

    Mitochondrial responses and changes of calcium ions in apoptotic insect SL-1 cells induced by Syngrapha falcifera multiple nuclear polyhedrosis virus (SfaMNPV) are reported in this paper. By using Rhodamine 123 as a fluorescent labeling probe, flow cytometry analysis and confocal laser scanning microscope observation we observed that the mitochondrial transmembrane potential (△Ψm) began to decrease in SL-1 cells at 4 h post infection and △Ψm reduced continuously with the extension of virus infection. Western blotting indicated that the Bcl-2 level in the mitochondria gradually declined and was down- regulated. Cells undergoing apoptosis were found to have an elevation of cytochrome c in the cytosol and a corresponding decrease in the mitochondria, which indicated that cytochrome c was released from mitochondria into cytosol. These results suggest that mitochondrion-mediated apoptotic signal transduction pathway exists in apoptotic insect cell induced by SfaMNPV. Cytosolic free calcium ([Ca2+]i) concentration rapidly increased after SfaMNPV infection and the elevated calcium was tested to come partly from extracelllular calcium ion influx. Flow cytometry analysis indicated that the apoptosis in SL-1 cells was not influenced by established cytosolic calcium clamped conditions and the EGTA inhibiting calcium influx. Therefore, neither the elevation of cytosolic calcium ion nor extracellular calcium entry was the inducing factor of apoptosis, which hinted that the depletion of ER Ca2+ store contributed to SL-1 cell apoptosis induced by SfaMNPV.

  20. An endogenous calcium-dependent, caspase-independent intranuclear degradation pathway in thymocyte nuclei: Antagonism by physiological concentrations of K+ ions

    International Nuclear Information System (INIS)

    Calcium ions have been implicated in apoptosis for many years, however the precise role of this ion in the cell death process remains incomplete. We have extensively examined the role of Ca2+ on nuclear degradation in vitro using highly purified nuclei isolated from non-apoptotic rat thymocytes. We show that these nuclei are devoid of CAD (caspase-activated DNase), and DNA degradation occurs independent of caspase activity. Serine proteases rather than caspase-3 appear necessary for this Ca2+-dependent DNA degradation in nuclei. We analyzed nuclei treated with various concentrations of Ca2+ in the presence of both a physiological (140 mM) and apoptotic (40 mM) concentration of KCl. Our results show that a 5-fold increase in Ca2+ is required to induce DNA degradation at the physiological KCl concentration compared to the lower, apoptotic concentration of the cation. Ca2+-induced internucleosomal DNA degradation was also accompanied by the release of histones, however the apoptotic-specific phosphorylation of histone H2B does not occur in these isolated nuclei. Interestingly, physiological concentrations of K+ inhibit both Ca2+-dependent DNA degradation and histone release suggesting that a reduction of intracellular K+ is necessary for this apoptosis-associated nuclear degradation in cells. Together, these data define an inherent caspase-independent catabolic pathway in thymocyte nuclei that is sensitive to physiological concentrations of intracellular cations

  1. Human cytomegalovirus entry into dendritic cells occurs via a macropinocytosis-like pathway in a pH-independent and cholesterol-dependent manner.

    Directory of Open Access Journals (Sweden)

    Fabienne Haspot

    Full Text Available Human cytomegalovirus (HCMV is a ubiquitous herpesvirus that is able to infect fibroblastic, epithelial, endothelial and hematopoietic cells. Over the past ten years, several groups have provided direct evidence that dendritic cells (DCs fully support the HCMV lytic cycle. We previously demonstrated that the C-type lectin dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN has a prominent role in the docking of HCMV on monocyte-derived DCs (MDDCs. The DC-SIGN/HCMV interaction was demonstrated to be a crucial and early event that substantially enhanced infection in trans, i.e., from one CMV-bearing cell to another non-infected cell (or trans-infection, and rendered susceptible cells fully permissive to HCMV infection. Nevertheless, nothing is yet known about how HCMV enters MDDCs. In this study, we demonstrated that VHL/E HCMV virions (an endothelio/dendrotropic strain are first internalized into MDDCs by a macropinocytosis-like process in an actin- and cholesterol-dependent, but pH-independent, manner. We observed the accumulation of virions in large uncoated vesicles with endosomal features, and the virions remained as intact particles that retained infectious potential for several hours. This trans-infection property was specific to MDDCs because monocyte-derived macrophages or monocytes from the same donor were unable to allow the accumulation of and the subsequent transmission of the virus. Together, these data allowed us to delineate the early mechanisms of the internalization and entry of an endothelio/dendrotropic HCMV strain into human MDDCs and to propose that DCs can serve as a "Trojan horse" to convey CMV from entry sites to other locations that may favor the occurrence of either latency or acute infection.

  2. Calcium - urine

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/003603.htm Calcium - urine To use the sharing features on this ... enable JavaScript. This test measures the amount of calcium in urine. All cells need calcium in order ...

  3. Calcium supplements

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/007477.htm Calcium supplements To use the sharing features on this page, please enable JavaScript. WHO SHOULD TAKE CALCIUM SUPPLEMENTS? Calcium is an important mineral for the ...

  4. Expression of Vibrio harveyi Acyl-ACP Synthetase Allows Efficient Entry of Exogenous Fatty Acids into the Escherichia coli Fatty Acid and Lipid A Synthetic Pathways

    Science.gov (United States)

    Jiang, Yanfang; Morgan-Kiss, Rachael M.; Campbell, John W.; Chan, Chi Ho; Cronan, John E.

    2010-01-01

    Although the Escherichia coli fatty acid synthesis (FAS) pathway is the best studied type II fatty acid synthesis system, a major experimental limitation has been the inability to feed intermediates into the pathway in vivo because exogenously-supplied free fatty acids are not efficiently converted to the acyl-acyl carrier protein (ACP) thioesters required by the pathway. We report that expression of Vibrio harveyi acyl-ACP synthetase (AasS), a soluble cytosolic enzyme that ligates free fatty acids to ACP to form acyl-ACPs, allows exogenous fatty acids to enter the E. coli fatty acid synthesis pathway. The free fatty acids are incorporated intact and can be elongated or directly incorporated into complex lipids by acyltransferases specific for acyl-ACPs. Moreover, expression of AasS strains and supplementation with the appropriate fatty acid restored growth to E. coli mutant strains that lack essential fatty acid synthesis enzymes. Thus, this strategy provides a new tool for circumventing the loss of enzymes essential for FAS function. PMID:20028080

  5. Calcium Oscillations

    OpenAIRE

    Dupont, Geneviève; Combettes, Laurent; Bird, Gary S.; Putney, James W.

    2011-01-01

    Calcium signaling results from a complex interplay between activation and inactivation of intracellular and extracellular calcium permeable channels. This complexity is obvious from the pattern of calcium signals observed with modest, physiological concentrations of calcium-mobilizing agonists, which typically present as sequential regenerative discharges of stored calcium, a process referred to as calcium oscillations. In this review, we discuss recent advances in understanding the underlyin...

  6. A novel receptor – ligand pathway for entry of Francisella tularensis in monocyte-like THP-1 cells: interaction between surface nucleolin and bacterial elongation factor Tu

    Directory of Open Access Journals (Sweden)

    Charbit Alain

    2008-09-01

    Full Text Available Abstract Background Francisella tularensis, the causative agent of tularemia, is one of the most infectious human bacterial pathogens. It is phagocytosed by immune cells, such as monocytes and macrophages. The precise mechanisms that initiate bacterial uptake have not yet been elucidated. Participation of C3, CR3, class A scavenger receptors and mannose receptor in bacterial uptake have been already reported. However, contribution of an additional, as-yet-unidentified receptor for F. tularensis internalization has been suggested. Results We show here that cell-surface expressed nucleolin is a receptor for Francisella tularensis Live Vaccine Strain (LVS and promotes LVS binding and infection of human monocyte-like THP-1 cells. The HB-19 pseudopeptide that binds specifically carboxy-terminal RGG domain of nucleolin inhibits LVS binding and infection of monocyte-like THP-1 cells. In a pull-down assay, elongation factor Tu (EF-Tu, a GTP-binding protein involved in protein translation, usually found in cytoplasm, was recovered among LVS bacterial membrane proteins bound on RGG domain of nucleolin. A specific polyclonal murine antibody was raised against recombinant LVS EF-Tu. By fluorescence and electron microscopy experiments, we found that a fraction of EF-Tu could be detected at the bacterial surface. Anti-EF-Tu antibodies reduced LVS binding to monocyte-like THP-1 cells and impaired infection, even in absence of complement and complement receptors. Interaction between EF-Tu and nucleolin was illustrated by two different pull-down assays using recombinant EF-Tu proteins and either RGG domain of nucleolin or cell solubilized nucleolin. Discussion Altogether, our results demonstrate that the interaction between surface nucleolin and its bacterial ligand EF-Tu plays an important role in Francisella tularensis adhesion and entry process and may therefore facilitate invasion of host tissues. Since phagosomal escape and intra-cytosolic multiplication of

  7. A membrane model for cytosolic calcium oscillations. A study using Xenopus oocytes.

    OpenAIRE

    Jafri, M S; Vajda, S.; Pasik, P; Gillo, B.

    1992-01-01

    Cytosolic calcium oscillations occur in a wide variety of cells and are involved in different cellular functions. We describe these calcium oscillations by a mathematical model based on the putative electrophysiological properties of the endoplasmic reticulum (ER) membrane. The salient features of our membrane model are calcium-dependent calcium channels and calcium pumps in the ER membrane, constant entry of calcium into the cytosol, calcium dependent removal from the cytosol, and buffering ...

  8. Foot-and-Mouth Disease Virus Induces Autophagosomes during Cell Entry via a Class III Phosphatidylinositol 3-Kinase-Independent Pathway

    OpenAIRE

    Berryman, Stephen; Brooks, Elizabeth; Burman, Alison; Hawes, Philippa; Roberts, Rebecca; Netherton, Christopher; Monaghan, Paul; Whelband, Matthew; Cottam, Eleanor; Elazar, Zvulun; Jackson, Terry; Wileman, Thomas

    2012-01-01

    Autophagy is an intracellular pathway that can contribute to innate antiviral immunity by delivering viruses to lysosomes for degradation or can be beneficial for viruses by providing specialized membranes for virus replication. Here, we show that the picornavirus foot-and-mouth disease virus (FMDV) induces the formation of autophagosomes. Induction was dependent on Atg5, involved processing of LC3 to LC3II, and led to a redistribution of LC3 from the cytosol to punctate vesicles indicative o...

  9. A contribution of budding yeast to unravel aging. Entry into quiescence relies on the transceptor Mtl1 by sensing nutrients and regulation of signaling pathways

    OpenAIRE

    Sundaram, Venkatraghavan

    2015-01-01

    Saccharomyces cerevisiae is a premier model system to study ageing in post mitotic cells. In this study, we show that Mtl1, member of the Cell Wall Integrity pathway (CWI), plays a positive role in Chronological Life Span (CLS). The absence of Mtl1 shortens CLS whereas its overexpression extends it. In mtl1 cells, we observe mitochondrial dysfunction during diauxic shift that is reflected in i) increase in uncoupled respiration associated to low oxygen consumption; ii) signific...

  10. Structure and Function of a Genetically Engineered Mimic of a Nonenveloped Virus Entry Intermediate

    Energy Technology Data Exchange (ETDEWEB)

    Banerjee, Manidipa; Speir, Jeffrey A.; Kwan, Maggie H.; Huang, Rick; Aryanpur, Peyman P.; Bothner, Brian; Johnson, John E. (UCSD); (Montana)

    2010-04-07

    Divalent metal ions are components of numerous icosahedral virus capsids. Flock House virus (FHV), a small RNA virus of the family Nodaviridae, was utilized as an accessible model system with which to address the effects of metal ions on capsid structure and on the biology of virus-host interactions. Mutations at the calcium-binding sites affected FHV capsid stability and drastically reduced virus infectivity, without altering the overall architecture of the capsid. The mutations also altered the conformation of gamma, a membrane-disrupting, virus-encoded peptide usually sequestered inside the capsid, by increasing its exposure under neutral pH conditions. Our data demonstrate that calcium binding is essential for maintaining a pH-based control on gamma exposure and host membrane disruption, and they reveal a novel rationale for the metal ion requirement during virus entry and infectivity. In the light of the phenotypes displayed by a calcium site mutant of FHV, we suggest that this mutant corresponds to an early entry intermediate formed in the endosomal pathway.

  11. Virus and calcium: an unexpected tandem to optimize insecticide efficacy.

    Science.gov (United States)

    Apaire-Marchais, Véronique; Ogliastro, Mylène; Chandre, Fabrice; Pennetier, Cédric; Raymond, Valérie; Lapied, Bruno

    2016-04-01

    The effective control of insect pests is based on the rational use of the most efficient and safe insecticide treatments. To increase the effects of classical insecticides and to avoid the ability of certain pest insects to develop resistance, it is essential to propose novel strategies. Previous studies have shown that calcium-dependent phosphorylation/dephosphorylation is now considered as a new cellular mechanism for increasing the target sensitivity to insecticides. Because it is known that virus entry is correlated with intracellular calcium concentration rise, this report attempts to present the most important data relevant to the feasibility of combining an insect virus such as baculovirus or densovirus with an insecticide. In this case, the insect virus is not used as a bioinsecticide but acts as a synergistic agent able to trigger calcium rise and to activate calcium-dependent intracellular signalling pathways involved in the increase of the membrane receptors and/or ion channels sensitivity to insecticides. This virus-insecticide mixture represents a promising alternative to optimize the efficacy of insecticides against insect pests while reducing the doses. PMID:26743399

  12. Role of Calcium Signaling in B Cell Activation and Biology.

    Science.gov (United States)

    Baba, Yoshihiro; Kurosaki, Tomohiro

    2016-01-01

    Increase in intracellular levels of calcium ions (Ca2+) is one of the key triggering signals for the development of B cell response to the antigen. The diverse Ca2+ signals finely controlled by multiple factors participate in the regulation of gene expression, B cell development, and effector functions. B cell receptor (BCR)-initiated Ca2+ mobilization is sourced from two pathways: one is the release of Ca2+ from the intracellular stores, endoplasmic reticulum (ER), and other is the prolonged influx of extracellular Ca2+ induced by depleting the stores via store-operated calcium entry (SOCE) and calcium release-activated calcium (CRAC) channels. The identification of stromal interaction molecule 1(STIM1), the ER Ca2+ sensor, and Orai1, a key subunit of the CRAC channel pore, has now provided the tools to understand the mode of Ca2+ influx regulation and physiological relevance. Herein, we discuss our current understanding of the molecular mechanisms underlying BCR-triggered Ca2+ signaling as well as its contribution to the B cell biological processes and diseases. PMID:26369772

  13. Do calcium-mediated cellular signalling pathways, prostaglandin E2 (PGE2), estrogen or progesterone receptor antagonists, or bacterial endotoxins affect bovine placental function in vitro?

    Science.gov (United States)

    Weems, Y S; Randel, R D; Carstens, G E; Welsh, T H; Weems, C W

    2004-04-01

    .05). Concentrations of PGE2 in media at 4 and 8 h were lower (P or = 0.05). PGF2alpha was increased (P < or = 0.05) by RU-486 at 8h and no other treatment affected PGF2alpha at 4 or 8 h (P < or = 0.05). In conclusion, modulators of cellular calcium signalling pathways given alone do not affect bovine placental progesterone secretion at the days studied and progesterone receptor-mediated events appear to suppress placental progesterone, PGF2alpha, and PGE2 secretion in cattle. In addition, PGE2 does not appear to regulate bovine placental progesterone secretion when the corpus luteum is functional and bacterial endotoxin does not appear to affect bovine placental secretion of PGF2alpha or PGE2. PMID:15287156

  14. Calcium ion channel and epilepsy

    Institute of Scientific and Technical Information of China (English)

    Yudan Lü; Weihong Lin; Dihui Ma

    2006-01-01

    OBJECTIVE: To review the relationship between calcium ion channel and epilepsy for well investigating the pathogenesis of epilepsy and probing into the new therapeutic pathway of epilepsy.DATA SOURCES: A computer-based online research Calcium ion channel and epilepsy related articles published between January 1994 and December 2006 in the CKNI and Wanfang database with the key words of "calcium influxion, epilepsy, calcium-channel blocker". The language was limited to Chinese. At the same time,related articles published between January 1993 and December 2006 in Pubmed were searched for on online with the key words of "calcium influxion, epilepsy" in English.STUDY SELECTION: The materials were selected firstly. Inclusive criteria: ① Studies related to calcium ion channel and the pat1hogenesis of epilepsy. ② Studies on the application of calcium ion channel blocker in the treatment of epilepsy. Exclusive criteria: repetitive or irrelated studies.DATA EXTRACTION: According to the criteria, 123 articles were retrieved and 93 were excluded due to repetitive or irrelated studies. Altogether 30 articles met the inclusive criteria, 11 of them were about the structure and characters of calcium ion channel, 10 about calcium ion channel and the pathogenesis of epilepsy and 9 about calcium blocker and the treatment of epilepsy.DATA SYNTHESIS: Calcium ion channels mainly consist of voltage dependent calcium channel and receptor operated calcium channel. Depolarization caused by voltage gating channel-induced influxion is the pathological basis of epileptic attack, and it is found in many studies that many anti-epileptic drugs have potential and direct effect to rivalizing voltage-dependent calcium ion channel.CONCLUSION: Calcium influxion plays an important role in the seizure of epilepsy. Some calcium antagonists seen commonly are being tried in the clinical therapy of epilepsy that is being explored, not applied in clinical practice. If there are enough evidences to

  15. 5-Hydroxytryptamino-induced calcium sparks in cultured rat stomach fundus smooth muscle cells

    Institute of Scientific and Technical Information of China (English)

    张小玲; 阎宏涛; 闫炀

    2003-01-01

    With a new fluorescence probe of Ca2+, STDIn-AM, 5-hydroxytryptamino (5-HT)-induced spontaneous calcium release events (calcium sparks) in cultured rat stomach fundus smooth muscle cells (SFSMC) are investigated by laser scanning confocal microscope. The mechanisms of initiation of Ca2+ sparks, propagating Ca2+ waves and their relation to E-C coupling are discussed. After the extracellular [Ca2+] is increased to 10 mmol/L, addition of 5-HT causes hot spots throughout the cytoplasm, which is brighter near the plasmalemma. The amplitude of the event is at least two times greater than the standard deviation of fluorescence intensity fluctuations measured in the neighboring region and the duration of the Ca2+ signal is over 100 ms. The results suggest that 5-HT acts by the way of 5-HT2 receptors on SFSMC, then through 5-HT2 receptors couples IP3/Ca2+ and DG/PKC double signal transduction pathways to cause Ca2+ release from intracellular Ca2+ stores and followed Ca2+ influx possibly through calcium release-activated calcium influx. The acceptor of activated 5-HT2 can also cause membrane depolarization, which then stimulates the L-type Ca2+ channels leading to Ca2+ influx. Thenthe local Ca2+ entry mentioned above activates ryanodine-sensitive Ca2+ releasechannels (RyR) on sarcoplasmic reticulum (SR) to cause local Ca2+ release events (Ca2+ sparks) through calcium-induced calcium release (CICR).

  16. Entry and incumbent innovation

    OpenAIRE

    Weinschenk, Philipp

    2010-01-01

    We explore how the threat of entry influences the innovation activity of an incumbent. We show that the incumbent’s investment is hump-shaped in the entry threat. When the entry threat is small and increases, the incumbent invests more to deter entry, or to make it unlikely. This is due to the entry deterrence effect. However, when the threat becomes huge, entry can no longer profitably be deterred or made unlikely and the investment becomes small. Then the Schumpeterian effect dominates. The...

  17. Entry Modes of Starbucks

    OpenAIRE

    Santamaría Sotillo, Beatriz; Ni, Shuang

    2008-01-01

    Topic:When an MNC seeks to enter a foreign country, it must choose the most appropriate entry mode for that specific market, such as exporting, licensing, a turnkey project, franchising, joint ventures or wholly-owned subsidiaries. There are many factors which affect the choice of entry modes. Influential factors contributing to the entry mode decision can have different degrees of impact for each particular country. As a consequence, an MNC has to use different entry modes in order to adapt ...

  18. Calcium Signaling Pathway Is Associated with the Long-Term Clinical Response to Selective Serotonin Reuptake Inhibitors (SSRI) and SSRI with Antipsychotics in Patients with Obsessive-Compulsive Disorder

    Science.gov (United States)

    Umehara, Hidehiro; Numata, Shusuke; Tajima, Atsushi; Nishi, Akira; Nakataki, Masahito; Imoto, Issei; Sumitani, Satsuki; Ohmori, Tetsuro

    2016-01-01

    Background Selective serotonin reuptake inhibitors (SSRI) are established first-line pharmacological treatments for obsessive-compulsive disorder (OCD), while antipsychotics are used as an augmentation strategy for SSRI in OCD patients who have either no response or a partial response to SSRI treatment. The goal of the present study was to identify genetic variants and pathways that are associated with the long-term clinical response of OCD patients to SSRI or SSRI with antipsychotics. Methods We first performed a genome-wide association study of 96 OCD patients to examine genetic variants contributing to the response to SSRI or SSRI with antipsychotics. Subsequently, we conducted pathway-based analyses by using Improved Gene Set Enrichment Analysis for Genome-wide Association Study (i-GSEA4GWAS) to examine the combined effects of genetic variants on the clinical response in OCD. Results While we failed to detect specific genetic variants associated with clinical responses to SSRI or to SSRI with an atypical antipsychotic at genome-wide levels of significance, we identified 8 enriched pathways for the SSRI treatment response and 5 enriched pathways for the treatment response to SSRI with an antipsychotic medication. Notably, the calcium signaling pathway was identified in both treatment responses. Conclusions Our results provide novel insight into the molecular mechanisms underlying the variability in clinical response to SSRI and SSRI with antipsychotics in OCD patients. PMID:27281126

  19. Fruit Calcium: Transport and Physiology

    Science.gov (United States)

    Hocking, Bradleigh; Tyerman, Stephen D.; Burton, Rachel A.; Gilliham, Matthew

    2016-01-01

    -regulated signaling pathways that control ripening would assist in addressing calcium deficiency disorders and improving fruit pathogen resistance. PMID:27200042

  20. Fruit Calcium: Transport and Physiology.

    Science.gov (United States)

    Hocking, Bradleigh; Tyerman, Stephen D; Burton, Rachel A; Gilliham, Matthew

    2016-01-01

    -regulated signaling pathways that control ripening would assist in addressing calcium deficiency disorders and improving fruit pathogen resistance. PMID:27200042

  1. Localization of large conductance calcium-activated potassium channels and their effect on calcitonin gene-related peptide release in the rat trigemino-neuronal pathway

    DEFF Research Database (Denmark)

    Wulf-Johansson, H.; Amrutkar, D.V.; Hay-Schmidt, Anders;

    2010-01-01

    Large conductance calcium-activated potassium (BK(Ca)) channels are membrane proteins contributing to electrical propagation through neurons. Calcitonin gene-related peptide (CGRP) is a neuropeptide found in the trigeminovascular system (TGVS). Both BK(Ca) channels and CGRP are involved in migraine...

  2. ATP stimulates calcium influx in primary astrocyte cultures

    International Nuclear Information System (INIS)

    The effect of ATP and other purines on 45Ca uptake was studied in primary cultures of rat astrocytes. Treatment of the cells with ATP for 1 to 30 min brought about an increase in cellular 45Ca. Stimulation of calcium influx by ATP was investigated using a 90 sec exposure to 45Ca and over a concentration range of 0.1 nM to 3 mM; a biphasic dose-response curve was obtained with EC50 values of 0.3 nM and 9 uM, indicating the presence of low and high affinity purinergic binding sites. Similar levels of 45Ca influx at 90 sec were observed with ATP, ADP and adenosine (all at 100 uM). Prior treatment of the cultures with LaCl3 blocked the purine-induced 45Ca influx. These findings indicate that one pathway for calcium entry in astrocytes involves purinergic receptor-operated, calcium channels

  3. Signaling pathways in ascidian oocyte maturation: the roles of cAMP/Epac, intracellular calcium levels, and calmodulin kinase in regulating GVBD.

    Science.gov (United States)

    Lambert, Charles C

    2011-01-01

    Most mature ascidian oocytes undergo germinal vesicle breakdown (GVBD) when released by the ovary into sea water (SW). Acidic SW blocks this but they can be stimulated by raising the pH, increasing intracellular cAMP levels by cell permeant forms, inhibiting its breakdown or causing synthesis. Boltenia villosa oocytes undergo GVBD in response to these drugs. However, the cAMP receptor protein kinase A (PKA) does not appear to be involved, as oocytes are not affected by the kinase inhibitor H-89. Also, the PKA independent Epac agonist 8CPT-2Me-cAMP stimulates GVBD in acidic SW. GVBD is inhibited in calcium free sea water (CaFSW). The intracellular calcium chelator BAPTA-AM blocks GVBD at 10 µM. GVBD is also inhibited when the ryanodine receptors (RYR) are blocked by tetracaine or ruthenium red but not by the IP(3) inhibitor D-609. However, dimethylbenzanthracene (DMBA), a protein kinase activator, stimulates GVBD in BAPTA, tetracaine or ruthenium red blocked oocytes. The calmodulin kinase inhibitor KN-93 blocks GVBD at 10 µM. This and preceding papers support the hypothesis that the maturation inducing substance (MIS) produced by the follicle cells in response to increased pH causes activation of a G protein which triggers cAMP synthesis. The cAMP then activates an Epac molecule, which causes an increase in intracellular calcium from the endoplasmic reticulum ryanodine receptor. The increased intracellular calcium subsequently activates calmodulin kinase, which causes an increase in cdc25 phosphatase activity, activating MPF and the progression of the oocyte into meiosis. PMID:21774024

  4. Effectiveness of a multidisciplinary critical pathway based on a computerised physician order entry system for ST-segment elevation myocardial infarction management in the emergency department: a retrospective observational study

    Science.gov (United States)

    Park, Yoo Seok; Chung, Sung Phil; You, Je Sung; Kim, Min Joung; Chung, Hyun Soo; Hong, Jung Hwa; Lee, Hye Sun; Wang, Jinwon; Park, Incheol

    2016-01-01

    Objectives The purpose of this study was to investigate whether a multidisciplinary organised critical pathway (CP) for ST-segment elevation myocardial infarction (STEMI) management can significantly attenuate differences in the duration from emergency department (ED) arrival to evaluation and treatment, regardless of the arrival time, by eliminating off-hour and weekend effects. Design Retrospective observational cohort study. Setting 2 tertiary academic hospitals. Participants Consecutive patients in the Fast Interrogation Rule for STEMI (FIRST) program. Interventions A study was conducted on patients in the FIRST program, which uses a computerised physician order entry (CPOE) system. The patient demographics, time intervals and clinical outcomes were analysed based on the arrival time at the ED: group 1, normal working hours on weekdays; group 2, off-hours on weekdays; group 3, normal working hours on weekends; and group 4, off-hours on weekends. Primary and secondary outcome measures Clinical outcomes categorised according to 30-day mortality, in-hospital mortality and the length of stay. Results The duration from door-to-data or FIRST activation did not differ significantly among the 4 groups. The median duration between arrival and balloon placement during percutaneous coronary intervention did not significantly exceed 90 min, and the proportions (89.6–95.1%) of patients with door-to-balloon times within 90 min did not significantly differ among the 4 groups, regardless of the ED arrival time (p=0.147). Moreover, no differences in the 30-day (p=0.8173) and in-hospital mortality (p=0.9107) were observed in patients with STEMI. Conclusions A multidisciplinary CP for STEMI based on a CPOE system can effectively decrease disparities in the door-to-data duration and proportions of patients with door-to-balloon times within 90 min, regardless of the ED arrival time. The application of a multidisciplinary CP may also help attenuate off-hour and weekend

  5. Calcium Carbonate

    Science.gov (United States)

    ... before being swallowed; do not swallow them whole. Drink a full glass of water after taking either the regular or chewable tablets or capsules. Some liquid forms of calcium carbonate must be shaken well before use.Do not ...

  6. Calcium Electroporation

    DEFF Research Database (Denmark)

    Frandsen, Stine Krog; Gibot, Laure; Madi, Moinecha;

    2015-01-01

    BACKGROUND: Calcium electroporation describes the use of high voltage electric pulses to introduce supraphysiological calcium concentrations into cells. This promising method is currently in clinical trial as an anti-cancer treatment. One very important issue is the relation between tumor cell kill...... efficacy-and normal cell sensitivity. METHODS: Using a 3D spheroid cell culture model we have tested the effect of calcium electroporation and electrochemotherapy using bleomycin on three different human cancer cell lines: a colorectal adenocarcinoma (HT29), a bladder transitional cell carcinoma (SW780......), and a breast adenocarcinoma (MDA-MB231), as well as on primary normal human dermal fibroblasts (HDF-n). RESULTS: The results showed a clear reduction in spheroid size in all three cancer cell spheroids three days after treatment with respectively calcium electroporation (p<0.0001) or...

  7. Calcium Calculator

    Science.gov (United States)

    ... Latvia - Lebanon - Libya - Lithuania - Luxembourg - Macedonia, Republic of - Malaysia - Malta - Mexico - Moldova - Morocco - Netherlands - New Zealand - Nigeria - ... and Statistics Popular content Calcium content of common foods What is Osteoporosis? The Board Introduction to Bone ...

  8. High-Yield Method for Isolation and Culture of Endothelial Cells from Rat Coronary Blood Vessels Suitable for Analysis of Intracellular Calcium and Nitric Oxide Biosynthetic Pathways

    Science.gov (United States)

    Nistri, Silvia; Mazzetti, Luca; Failli, Paola

    2002-01-01

    We describe here a method for isolating endothelial cells from rat heart blood vessels by means of coronary microperfusion with collagenase. This methods makes it possible to obtain high amounts of endothelial cells in culture which retain the functional properties of their in vivo counterparts, including the ability to uptake fluorescently-labeled acetylated low-density lipoproteins and to respond to vasoactive agents by modulating intracellular calcium and by upregulating intrinsic nitric oxide generation. The main advantages of our technique are: (i) good reproducibility, (ii) accurate sterility that can be maintained throughout the isolation procedure and (iii) high yield of pure endothelial cells, mainly due to microperfusion and temperature-controlled incubation with collagenase which allow an optimal distribution of this enzyme within the coronary vascular bed. PMID:12734571

  9. A Differential Role for Macropinocytosis in Mediating Entry of the Two Forms of Vaccinia Virus into Dendritic Cells

    Science.gov (United States)

    Sandgren, Kerrie J.; Wilkinson, John; Miranda-Saksena, Monica; McInerney, Gerald M.; Byth-Wilson, Karen; Robinson, Phillip J.; Cunningham, Anthony L.

    2010-01-01

    Vaccinia virus (VACV) is being developed as a recombinant viral vaccine vector for several key pathogens. Dendritic cells (DCs) are specialised antigen presenting cells that are crucial for the initiation of primary immune responses; however, the mechanisms of uptake of VACV by these cells are unclear. Therefore we examined the binding and entry of both the intracellular mature virus (MV) and extracellular enveloped virus (EV) forms of VACV into vesicular compartments of monocyte-derived DCs. Using a panel of inhibitors, flow cytometry and confocal microscopy we have shown that neither MV nor EV binds to the highly expressed C-type lectin receptors on DCs that are responsible for capturing many other viruses. We also found that both forms of VACV enter DCs via a clathrin-, caveolin-, flotillin- and dynamin-independent pathway that is dependent on actin, intracellular calcium and host-cell cholesterol. Both MV and EV entry were inhibited by the macropinocytosis inhibitors rottlerin and dimethyl amiloride and depended on phosphotidylinositol-3-kinase (PI(3)K), and both colocalised with dextran but not transferrin. VACV was not delivered to the classical endolysosomal pathway, failing to colocalise with EEA1 or Lamp2. Finally, expression of early viral genes was not affected by bafilomycin A, indicating that the virus does not depend on low pH to deliver cores to the cytoplasm. From these collective results we conclude that VACV enters DCs via macropinocytosis. However, MV was consistently less sensitive to inhibition and is likely to utilise at least one other entry pathway. Definition and future manipulation of these pathways may assist in enhancing the activity of recombinant vaccinia vectors through effects on antigen presentation. PMID:20421949

  10. A differential role for macropinocytosis in mediating entry of the two forms of vaccinia virus into dendritic cells.

    Directory of Open Access Journals (Sweden)

    Kerrie J Sandgren

    2010-04-01

    Full Text Available Vaccinia virus (VACV is being developed as a recombinant viral vaccine vector for several key pathogens. Dendritic cells (DCs are specialised antigen presenting cells that are crucial for the initiation of primary immune responses; however, the mechanisms of uptake of VACV by these cells are unclear. Therefore we examined the binding and entry of both the intracellular mature virus (MV and extracellular enveloped virus (EV forms of VACV into vesicular compartments of monocyte-derived DCs. Using a panel of inhibitors, flow cytometry and confocal microscopy we have shown that neither MV nor EV binds to the highly expressed C-type lectin receptors on DCs that are responsible for capturing many other viruses. We also found that both forms of VACV enter DCs via a clathrin-, caveolin-, flotillin- and dynamin-independent pathway that is dependent on actin, intracellular calcium and host-cell cholesterol. Both MV and EV entry were inhibited by the macropinocytosis inhibitors rottlerin and dimethyl amiloride and depended on phosphotidylinositol-3-kinase (PI(3K, and both colocalised with dextran but not transferrin. VACV was not delivered to the classical endolysosomal pathway, failing to colocalise with EEA1 or Lamp2. Finally, expression of early viral genes was not affected by bafilomycin A, indicating that the virus does not depend on low pH to deliver cores to the cytoplasm. From these collective results we conclude that VACV enters DCs via macropinocytosis. However, MV was consistently less sensitive to inhibition and is likely to utilise at least one other entry pathway. Definition and future manipulation of these pathways may assist in enhancing the activity of recombinant vaccinia vectors through effects on antigen presentation.

  11. Calcium in plant cells

    Directory of Open Access Journals (Sweden)

    V. V. Schwartau

    2014-04-01

    connect ion conformationally rearranged, thus passing the signal through the chain of intermediaries. The most important function of calcium is its participation in many cell signaling pathways. Channels, pumps, gene expression, synthesis of alkaloids, protective molecules, NO etc. respond to changes in [Ca2+]cyt, while transductors are represented by a number of proteins. The universality of calcium is evident in the study in connection with other signaling systems, such as NO, which is involved in the immune response and is able to control the feedback activity of protein activators channels, producing nitric oxide. Simulation of calcium responses can determine the impact of key level and their regulation, and also depends on the type of stimulus and the effector protein that specifically causes certain changes. Using spatiotemporal modeling, scientists showed that the key components for the formation of Ca2+ bursts are the internal and external surfaces of the nucleus membrane. The research was aimed at understanding of the mechanisms of influence of Ca2+-binding components on Ca2+ oscillations. The simulation suggests the existence of a calcium depot EPR with conjugated lumen of the nucleus which releases its contents to nucleoplasm. With these assumptions, the mathematical model was created and confirmed experimentally. It describes the oscillation of nuclear calcium in root hairs of Medicago truncatula at symbiotic relationship of plants and fungi (rhizobia. Calcium oscillations are present in symbiotic relationships of the cortical layer of plant root cells. Before penetration of bacteria into the cells, slow oscillations of Ca2+ are observed, but with their penetration into the cells the oscillation frequency increases. These processes take place by changing buffer characteristics of the cytoplasm caused by signals from microbes, such as Nod-factor available after penetration of bacteria through the cell wall. Thus, the basic known molecular mechanisms for

  12. A mathematical model of T lymphocyte calcium dynamics derived from single transmembrane protein properties

    Directory of Open Access Journals (Sweden)

    Christine Dorothee Schmeitz

    2013-09-01

    Full Text Available Fate decision processes of T lymphocytes are crucial for health and disease. Whether a T lymphocyte is activated, divides, gets anergic or initiates apoptosis depends on extracellular triggers and intracellular signalling. Free cytosolic calcium dynamics plays an important role in this context. The relative contributions of store-derived calcium entry and calcium entry from extracellular space to T lymphocyte activation are still a matter of debate. Here we develop a quantitative mathematical model of T lymphocyte calcium dynamics in order to establish a tool which allows to disentangle cause-effect relationships between ion fluxes and observed calcium time courses. The model is based on single transmembrane protein characteristics which have been determined in independent experiments. This reduces the number of unknown parameters in the model to a minimum and ensures the predictive power of the model. Simulation results are subsequently used for an analysis of whole cell calcium dynamics measured under various experimental conditions. The model accounts for a variety of these conditions, which supports the suitability of the modelling approach. The simulation results suggest a model in which calcium dynamics dominantly relies on the opening of channels in calcium stores while calcium entry through calcium-release activated channels (CRAC is more associated with the maintenance of the T lymphocyte calcium levels and prevents the cell from calcium depletion. Our findings indicate that CRAC guarantees a long-term stable calcium level which is required for cell survival and sustained calcium enhancement.

  13. Influence of reactive oxygen species and RhoA/ROCK pathway on calcium concentration and calcium sensitivity of vascular smooth muscle cells%活性氧与 RhoA/ROCK 信号通路对血管平滑肌细胞钙浓度及钙敏感性的影响

    Institute of Scientific and Technical Information of China (English)

    闫莹; 杨朝; 汪涛

    2015-01-01

    Reactive oxygen species (ROS)is an important class of second messengers in vivo,and can be induced greatly by ischemia and hypoxia.Hypoxia signal can trigger the contraction of vascular smooth muscle cells by regulating the cytoplasmic free calcium concentration via ROS,hypoxia may also activate RhoA/ROCK signaling pathway by ROS and then regulate the calcium sensitivity.Deep research on ROS and RhoA/ROCK pathway will illustrate the pathogenesis of hypoxic pulmonary vasoconstriction and pulmonary hypertension,providing new ideas for the treatment of hypoxic pulmonary hypertension.%活性氧(ROS)是体内一类重要的第二信使,能在缺血缺氧的诱导下大量产生。缺氧信号能通过 ROS 调节血管平滑肌细胞内的钙浓度,从而引起其收缩反应;缺氧还有可能通过 ROS 激活 RhoA/ROCK 信号通路,对钙敏感性进行调节。对 ROS 以及 RhoA/ROCK 信号通路进行深入的研究,可以阐明缺氧性肺血管收缩以及肺动脉高压的发病机制,为缺氧性肺动脉高压的治疗提供新的思路。

  14. Lobbying on Entry

    OpenAIRE

    Perotti, E.C.; Volpin, P.

    2004-01-01

    We develop a model of endogenous lobby formation in which wealth inequality and political accountability undermine entry and financial development. Incumbents seek a low level of effective investor protection to prevent potential entrants from raising capital. They succeed because they can promise larger political contributions than the entrants due to the higher rents earned with less competition. Entry and investor protection improve when wealth distribution becomes less unequal, and the po...

  15. Entry Threat in Duopoly

    OpenAIRE

    Peitz, Martin

    1996-01-01

    Abstract: An oligopolistic market with vertical product differentiation is parametrized in cost parameters. This allows me to study the impact of the technology of the firms (cost parameters) on market structure, conduct, and performance. Firms which differ only by the order of the sequential move to choose a quality use sophisticated entry deterring or entry accomodating strategies. I show that infinitesimal changes in the cost parameters can generate discontinuities in market profits. In pa...

  16. Calcium pyrophosphate arthritis

    Science.gov (United States)

    Calcium pyrophosphate dihydrate deposition disease; CPPD disease; Acute CPPD arthritis; Pseudogout ... Calcium pyrophosphate arthritis is caused by the collection of salt called calcium pyrophosphate dihydrate (CPPD). The buildup ...

  17. Calcium and bones

    Science.gov (United States)

    Bone strength and calcium ... calcium (as well as phosphorus) to make healthy bones. Bones are the main storage site of calcium in ... your body does not absorb enough calcium, your bones can get weak or will not grow properly. ...

  18. Get Enough Calcium

    Science.gov (United States)

    ... Calcium Print This Topic En español Get Enough Calcium Browse Sections The Basics Overview Foods and Vitamins ... 2 of 4 sections Take Action! Take Action: Calcium Sources Protect your bones – get plenty of calcium ...

  19. Calcium carbonate overdose

    Science.gov (United States)

    Tums overdose; Calcium overdose ... Calcium carbonate can be dangerous in large amounts. ... Some products that contain calcium carbonate are certain: ... and mineral supplements Other products may also contain calcium ...

  20. The role of voltage-gated calcium channels in neurotransmitter phenotype specification: Coexpression and functional analysis in Xenopus laevis

    OpenAIRE

    Lewis, Brittany B.; Miller, Lauren E.; Herbst, Wendy A; Saha, Margaret S.

    2014-01-01

    Calcium activity has been implicated in many neurodevelopmental events, including the specification of neurotransmitter phenotypes. Higher levels of calcium activity lead to an increased number of inhibitory neural phenotypes, whereas lower levels of calcium activity lead to excitatory neural phenotypes. Voltage-gated calcium channels (VGCCs) allow for rapid calcium entry and are expressed during early neural stages, making them likely regulators of activity-dependent neurotransmitter phenoty...

  1. Structures of apicomplexan calcium-dependent protein kinases reveal mechanism of activation by calcium

    Energy Technology Data Exchange (ETDEWEB)

    Wernimont, Amy K; Artz, Jennifer D.; Jr, Patrick Finerty; Lin, Yu-Hui; Amani, Mehrnaz; Allali-Hassani, Abdellah; Senisterra, Guillermo; Vedadi, Masoud; Tempel, Wolfram; Mackenzie, Farrell; Chau, Irene; Lourido, Sebastian; Sibley, L. David; Hui, Raymond (Toronto); (WU-MED)

    2010-09-21

    Calcium-dependent protein kinases (CDPKs) have pivotal roles in the calcium-signaling pathway in plants, ciliates and apicomplexan parasites and comprise a calmodulin-dependent kinase (CaMK)-like kinase domain regulated by a calcium-binding domain in the C terminus. To understand this intramolecular mechanism of activation, we solved the structures of the autoinhibited (apo) and activated (calcium-bound) conformations of CDPKs from the apicomplexan parasites Toxoplasma gondii and Cryptosporidium parvum. In the apo form, the C-terminal CDPK activation domain (CAD) resembles a calmodulin protein with an unexpected long helix in the N terminus that inhibits the kinase domain in the same manner as CaMKII. Calcium binding triggers the reorganization of the CAD into a highly intricate fold, leading to its relocation around the base of the kinase domain to a site remote from the substrate binding site. This large conformational change constitutes a distinct mechanism in calcium signal-transduction pathways.

  2. Time card entry system

    Energy Technology Data Exchange (ETDEWEB)

    Montierth, B.S.

    1996-05-01

    The Time Card Entry System was developed to interface with the DOE Headquarters Electronic Time and Attendance (ETA) system. It features pop-up window pick lists for Work Breakdown Structure Numbers and Hour Codes and has extensive processing that ensures that time and attendance reported by the employee fulfills US Government/OMB requirements before Timekeepers process the data at the end of the two week payroll cycle using ETA. Tours of Duty (e.g. ten hour day, four day week with Friday through Sunday off), established in the ETA system, are imported into the Time Card Entry System by the Timekeepers. An individual`s Tour of Duty establishes the basis for validation of time of day and number of hours worked per day. At the end of the two week cycle, data is exported by the Timekeepers from the Time Card Entry System into ETA data files.

  3. Computational study of a calcium release-activated calcium channel

    Science.gov (United States)

    Talukdar, Keka; Shantappa, Anil

    2016-05-01

    The naturally occurring proteins that form hole in membrane are commonly known as ion channels. They play multiple roles in many important biological processes. Deletion or alteration of these channels often leads to serious problems in the physiological processes as it controls the flow of ions through it. The proper maintenance of the flow of ions, in turn, is required for normal health. Here we have investigated the behavior of a calcium release-activated calcium ion channel with pdb entry 4HKR in Drosophila Melanogaster. The equilibrium energy as well as molecular dynamics simulation is performed first. The protein is subjected to molecular dynamics simulation to find their energy minimized value. Simulation of the protein in the environment of water and ions has given us important results too. The solvation energy is also found using Charmm potential.

  4. Reduced levels of intracellular calcium releasing in spermatozoa from asthenozoospermic patients

    Directory of Open Access Journals (Sweden)

    García Juan F

    2009-02-01

    Full Text Available Abstract Background Asthenozoospermia is one of the most common findings present in infertile males characterized by reduced or absent sperm motility, but its aetiology remains unknown in most cases. In addition, calcium is one of the most important ions regulating sperm motility. In this study we have investigated the progesterone-evoked intracellular calcium signal in ejaculated spermatozoa from men with normospermia or asthenozoospermia. Methods Human ejaculates were obtained from healthy volunteers and asthenospermic men by masturbation after 4–5 days of abstinence. For determination of cytosolic free calcium concentration, spermatozoa were loaded with the fluorescent ratiometric calcium indicator Fura-2. Results Treatment of spermatozoa from normospermic men with 20 micromolar progesterone plus 1 micromolar thapsigargin in a calcium free medium induced a typical transient increase in cytosolic free calcium concentration due to calcium release from internal stores. Similar results were obtained when spermatozoa were stimulated with progesterone alone. Subsequent addition of calcium to the external medium evoked a sustained elevation in cytosolic free calcium concentration indicative of capacitative calcium entry. However, when progesterone plus thapsigargin were administered to spermatozoa from patients with asthenozoospermia, calcium signal and subsequent calcium entry was much smaller compared to normospermic patients. As expected, pretreatment of normospermic spermatozoa with both the anti-progesterone receptor c262 antibody and with progesterone receptor antagonist RU-38486 decreased the calcium release induced by progesterone. Treatment of spermatozoa with cytochalasin D or jasplakinolide decreased the calcium entry evoked by depletion of internal calcium stores in normospermic patients, whereas these treatments proved to be ineffective at modifying the calcium entry in patients with asthenozoospermia. Conclusion Our results suggest

  5. Exclusive Dealing and Entry

    OpenAIRE

    João Leão

    2008-01-01

    This paper examines the use of exclusive dealing agreements to prevent the entry of rival firms. An exclusive dealing agreement is a contract between a buyer and a seller where the buyer commits to buy a good exclusively from the seller. One main concern of the literature is to explain how an incumbent seller is able to persuade the buyers to sign an exclusive dealing agreement that deters the entry of a more efficient rival seller. We propose a new explanation when the buyers are downstream ...

  6. Expression of TRPC3 in Chinese Hamster Ovary Cells Results in Calcium-activated Cation Currents Not Related to Store Depletion

    OpenAIRE

    Zitt, Christof; Obukhov, Alexander G.; Strübing, Carsten; Zobel, Andrea; Kalkbrenner, Frank; Lückhoff, Andreas; Schultz, Günter

    1997-01-01

    TRPC3 (or Htrp3) is a human member of the trp family of Ca2+-permeable cation channels. Since expression of TRPC3 cDNA results in markedly enhanced Ca2+ influx in response to stimulation of membrane receptors linked to phospholipase C (Zhu, X., J. Meisheng, M. Peyton, G. Bouley, R. Hurst, E. Stefani, and L. Birnbaumer. 1996. Cell. 85:661–671), we tested whether TRPC3 might represent a Ca2+ entry pathway activated as a consequence of depletion of intracellular calcium stores. CHO cells express...

  7. Targeting HCV Entry For Development of Therapeutics

    Directory of Open Access Journals (Sweden)

    Jeffrey F. McKelvy

    2010-08-01

    Full Text Available Recent progress in defining the molecular mechanisms of Hepatitis C Virus (HCV entry affords the opportunity to exploit new viral and host targets for therapeutic intervention. Entry inhibitors would limit the expansion of the infected cell reservoir, and would complement the many replication inhibitors now under development. The current model for the pathway of entry involves the initial docking of the virus onto the cell surface through interactions of virion envelope and associated low density lipoproteins (LDL with cell surface glycosaminoglycans and lipoprotein receptors, followed by more specific utilization with other hepatocyte membrane proteins: Scavenger Receptor Class B type 1 (SR-BI, CD81, Claudin 1 (CLDN1 and Occludin (OCLN. The use of blockers of these interactions, e.g. specific antibodies, suggests that inhibition of any one step in the entry pathway can inhibit infection. Despite this knowledge base, the tools for compound screening, HCV pseudoparticles (HCVpp and cell culture virus (HCVcc, and the ability to adapt them to industrial use are only recently available and as a result drug discovery initiatives are in their infancy. Several therapies aiming at modulating the virus envelope to prevent host cell binding are in early clinical testing. The first test case for blocking a cellular co-receptor is an SR-BI modulator. ITX 5061, an orally active small molecule, targets SR-BI and has shown potent antiviral activity against HCVpp and HCVcc. ITX 5061 has exhibited good safety in previous clinical studies, and is being evaluated in the clinic in chronic HCV patients and patients undergoing liver transplantation. Entry inhibitors promise to be valuable players in the future development of curative therapy against HCV.

  8. Calcium-mediated increased expression of fibroblast growth factor-2 acts through NF-κB and PGE2/EP4 receptor signaling pathways in cementoblasts.

    Science.gov (United States)

    Kanaya, Sousuke; Nemoto, Eiji; Sakisaka, Yukihiko; Shimauchi, Hidetoshi

    2013-10-01

    We reported previously that cementoblasts are provided with sensing mechanisms for extracellular Ca2+ and that elevated extracellular Ca2+ increases fibroblast growth factor-2 (FGF-2) gene and protein expression levels via a cyclic AMP/protein kinase A (PKA) dependent pathway. In the present study, we found that stimulation of murine cementoblasts with 10 mM CaCl2 induced cyclooxygenase-2 (COX-2) gene expression and prostaglandin E2 (PGE2) biosynthesis. NS-398, a COX-2 inhibitor, significantly reduced CaCl2-induced increase in Fgf-2 gene expression, indicating that PGE2 synthesized by COX-2 may be involved in FGF-2 induction. The inhibitory effect of NS-398 was restored completely by the addition of PGE2 receptor 4 (E-prostanoid receptor 4, called EP4) agonist, but not agonists for EP1, EP2, and EP3. Furthermore, EP4 antagonist significantly reduced CaCl2-induced Fgf-2 induction, suggesting that it is mediated by EP4 activation. However, stimulation with EP4 agonist alone in the absence of CaCl2 had no effect on the Fgf-2 induction, indicating that EP4 signaling alone is not sufficient. CaCl2 also upregulated gene expression levels of Ep4 and Cox-2, as well as Fgf-2 and induction of these genes was abolished by pretreatment with BMS-345541, a nuclear factor-κB (NF-κB) inhibitor, indicating that NF-κB signaling triggered by CaCl2 is indispensable for FGF-2 induction. Furthermore, CaCl2-induced Fgf-2 induction was synergistically enhanced by the addition of EP4 agonist. This indicates that the signaling triggered via CaCl2 and its combination with EP4 agonist may be useful as a novel strategy for periodontal regeneration. PMID:23851295

  9. Deployable Entry-system Project

    Data.gov (United States)

    National Aeronautics and Space Administration — The Deployable Entry-system ProjecT (ADEPT) will develop requirements for the ADEPT flight test.  Prior entry systems used high mass thermal protection...

  10. Analyzing Modes of Foreign Entry

    OpenAIRE

    Müller, Thomas

    2001-01-01

    This paper studies the entry decision of a multinational enterprise into a foreign market. Two alternative entry modes for a foreign direct investment are considered: Greenfield investment versus acquisition. In contrast to existing approaches, the acquisition price and the profits under both entry modes are endogenously determined. Interestingly, we find that the optimal entry mode decision is a ected by the competition intensity in the market in a non-monotonic way. When markets are very mu...

  11. Auranofin, an Anti-Rheumatic Gold Compound, Modulates Apoptosis by Elevating the Intracellular Calcium Concentration ([Ca2+]i) in MCF-7 Breast Cancer Cells

    International Nuclear Information System (INIS)

    Auranofin, a transition metal complex is used for the treatment of rheumatoid arthritis but is also an effective anti-cancer drug. We investigate the effects of Auranofin in inducing cell death by apoptosis and whether these changes are correlated to changes of intracellular calcium concentration ([Ca2+]i) in breast cancer cells (MCF-7). Cytotoxicity of Auranofin was evaluated using MTS assay and the Trypan blue dye exclusion method. With fluorescent dyes SR-FLICA and 7-AAD apoptotic death and necrotic death were differentiated by Flow cytometry. A concentration dependent decrease in the viability occurred and cells were shifted to the apoptotic phase. Intracellular calcium ([Ca2+]i) was recorded using florescence microscopy and a calcium sensitive dye (Fluo-4 AM) with a strong negative correlation (r = −0.713) to viability. Pharmacological modulators 2-APB (50 μM), Nimodipine (10 μM), Caffeine (10 mM), SKF 96365(20 μM) were used to modify calcium entry and release. Auranofin induced a sustained increase of [Ca2+]i in a concentration and time dependent manner. The use of different blockers of calcium channels did not reveal the source for the rise of [Ca2+]i. Overall, elevation of [Ca2+]i by Auranofin might be crucial for triggering Ca2+-dependent apoptotic pathways. Therefore, in anti-cancer therapy, modulating [Ca2+]i should be considered as a crucial factor for the induction of cell death in cancer cells

  12. Auranofin, an Anti-Rheumatic Gold Compound, Modulates Apoptosis by Elevating the Intracellular Calcium Concentration ([Ca2+]i in MCF-7 Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Elizabeth Varghese

    2014-11-01

    Full Text Available Auranofin, a transition metal complex is used for the treatment of rheumatoid arthritis but is also an effective anti-cancer drug. We investigate the effects of Auranofin in inducing cell death by apoptosis and whether these changes are correlated to changes of intracellular calcium concentration ([Ca2+]i in breast cancer cells (MCF-7. Cytotoxicity of Auranofin was evaluated using MTS assay and the Trypan blue dye exclusion method. With fluorescent dyes SR-FLICA and 7-AAD apoptotic death and necrotic death were differentiated by Flow cytometry. A concentration dependent decrease in the viability occurred and cells were shifted to the apoptotic phase. Intracellular calcium ([Ca2+]i was recorded using florescence microscopy and a calcium sensitive dye (Fluo-4 AM with a strong negative correlation (r = −0.713 to viability. Pharmacological modulators 2-APB (50 μM, Nimodipine (10 μM, Caffeine (10 mM, SKF 96365(20 μM were used to modify calcium entry and release. Auranofin induced a sustained increase of [Ca2+]i in a concentration and time dependent manner. The use of different blockers of calcium channels did not reveal the source for the rise of [Ca2+]i. Overall, elevation of [Ca2+]i by Auranofin might be crucial for triggering Ca2+-dependent apoptotic pathways. Therefore, in anti-cancer therapy, modulating [Ca2+]i should be considered as a crucial factor for the induction of cell death in cancer cells.

  13. Paclitaxel Induces Apoptosis in Breast Cancer Cells through Different Calcium—Regulating Mechanisms Depending on External Calcium Conditions

    Directory of Open Access Journals (Sweden)

    Zhi Pan

    2014-02-01

    Full Text Available Previously, we reported that endoplasmic reticulum calcium stores were a direct target for paclitaxel initiation of apoptosis. Furthermore, the actions of paclitaxel attenuated Bcl-2 resistance to apoptosis through endoplasmic reticulum-mediated calcium release. To better understand the calcium-regulated mechanisms of paclitaxel-induced apoptosis in breast cancer cells, we investigated the role of extracellular calcium, specifically; whether influx of extracellular calcium contributed to and/or was necessary for paclitaxel-induced apoptosis. Our results demonstrated that paclitaxel induced extracellular calcium influx. This mobilization of extracellular calcium contributed to subsequent cytosolic calcium elevation differently, depending on dosage. Under normal extracellular calcium conditions, high dose paclitaxel induced apoptosis-promoting calcium influx, which did not occur in calcium-free conditions. In the absence of extracellular calcium an “Enhanced Calcium Efflux” mechanism in which high dose paclitaxel stimulated calcium efflux immediately, leading to dramatic cytosolic calcium decrease, was observed. In the absence of extracellular calcium, high dose paclitaxel’s stimulatory effects on capacitative calcium entry and apoptosis could not be completely restored. Thus, normal extracellular calcium concentrations are critical for high dose paclitaxel-induced apoptosis. In contrast, low dose paclitaxel mirrored controls, indicating that it occurs independent of extracellular calcium. Thus, extracellular calcium conditions only affect efficacy of high dose paclitaxel-induced apoptosis.

  14. Corruption, Entry and Pollution

    OpenAIRE

    Eleni Stathopoulou; Dimitrios Varvarigos

    2013-01-01

    We model an economy where imperfectly competitive firms choose whether to employ a dirty technology and pay an emission tax or employ a clean technology and incur the cost of its adoption. Bureaucrats who are entrusted with the task of monitoring the emissions of each firm, are corruptible in the sense that they may accept bribes in order to mislead authorities on the firms’ actual emissions. Market entry is an important element in the relation between corruption and pollution. Particularly, ...

  15. Intracellular calcium ions as regulators of renal tubular sodium transport.

    Science.gov (United States)

    Windhager, E; Frindt, G; Yang, J M; Lee, C O

    1986-09-15

    This review addresses the putative role of intracellular calcium ions in the regulation of sodium transport by renal tubules. Cytoplasmic calcium-ion activities in proximal tubules of Necturus are less than 10(-7) M and can be increased by lowering the electrochemical potential gradient for sodium ions across the peritubular cell membrane, or by addition of quinidine or ionomycin to peritubular fluid. Whereas lowering of the peritubular Na concentration increases cytosolic [Ca++] and [H+], ionomycin, a calcium ionophore, raises intracellular [Ca++] without decreasing pHi. The intracellular calcium-ion level is maintained by transport processes in the plasma membrane and membranes of intracellular organelles, as well as by calcium-binding proteins. Calcium ions inhibit net transport of sodium by reducing the rate of sodium entry across the luminal cell membrane. In the collecting tubule this inhibition is caused, at least in part, by an indirect reduction in the activity of the amiloride-sensitive sodium channel. PMID:2430134

  16. Calcium and bones (image)

    Science.gov (United States)

    Calcium is one of the most important minerals for the growth, maintenance, and reproduction of the human ... body, are continually being re-formed and incorporate calcium into their structure. Calcium is essential for the ...

  17. Coronary Calcium Scan

    Science.gov (United States)

    ... the NHLBI on Twitter. What Is a Coronary Calcium Scan? A coronary calcium scan is a test ... you have calcifications in your coronary arteries. Coronary Calcium Scan Figure A shows the position of the ...

  18. Calcium hydroxide poisoning

    Science.gov (United States)

    Hydrate - calcium; Lime milk; Slaked lime ... Calcium hydroxide ... These products contain calcium hydroxide: Cement Limewater Many industrial solvents and cleaners (hundreds to thousands of construction products, flooring strippers, brick cleaners, cement ...

  19. Calcium source (image)

    Science.gov (United States)

    Getting enough calcium to keep bones from thinning throughout a person's life may be made more difficult if that person has ... as a tendency toward kidney stones, for avoiding calcium-rich food sources. Calcium deficiency also effects the ...

  20. Calcium in diet

    Science.gov (United States)

    Diet - calcium ... Calcium is one of the most important minerals for the human body. It helps form and maintain healthy teeth and bones. A proper level of calcium in the body over a lifetime can help ...

  1. Calcium Pyrophosphate Deposition (CPPD)

    Science.gov (United States)

    ... Patient / Caregiver Diseases & Conditions Calcium Pyrophosphate Deposition (CPPD) Calcium Pyrophosphate Deposition (CPPD) Fast Facts The risk of ... young people, too. Proper diagnosis depends on detecting calcium pyrophosphate crystals in the fluid of an affected ...

  2. Synthesis of calcium hydroxyapatite from calcium carbonate and different orthophosphate sources: A comparative study

    International Nuclear Information System (INIS)

    Highlights: ► Calcium hydroxyapatite was synthesized from CaCO3 and four orthophosphates. ► Only H3PO4 led to the complete precipitation of orthophosphate species. ► H3PO4 was also the most efficient for calcium dissolution. ► Reaction pathway was dissolution-precipitation accompanied by agglomeration step. - Abstract: The synthesis of calcium hydroxyapatite (Ca-HA) starting from calcium carbonate and different orthophosphate sources, including orthophosphoric acid, potassium, sodium and ammonium dihydrogen orthophosphates, was investigated under ambient conditions. The reaction started with calcium carbonate dissolution in an acid medium, followed by rapid precipitation of calcium cations with orthophosphate species to form calcium phosphate based particles which were in the size range of 0.4–1 μm. These particles then agglomerated into much larger ones, up to 350 μm in diameter (aggregates). These aggregates possessed an unstable porous structure which was responsible for the porosity of the final products. The highest specific surface area and pore volume were obtained with potassium dihydrogen orthophosphate. On the other hand, orthophosphoric acid led to the highest dissolution of calcium carbonate and the complete precipitation of orthophosphate species. Under ambient conditions, calcium phosphate based solid products of low crystallinity were formed. Different intermediates were identified and a reaction pathway proposed.

  3. P12 - PTHC1: A Continuing Cell Line Expressing PTH and Genes Involved in Calcium Homeostasis

    OpenAIRE

    Fabbri, S.; Mazzotta, C.; Ciuffi, S.; Mavilia, C.; Galli, G.; Zonefrati, R; Strigoli, D.; Cavalli, L.; Cavalli, T.; Brandi, M.L.

    2010-01-01

    The main organs regulating serum levels of ionised calcium (Ca2+) are the parathyroids, which are composed of two different cell types: chief cells and oxyphil cells. Chief cells, through the calcium sensing receptor (CaSR), are affected by changes in calcium concentration, modifying PTH secretion in proportion to calcium levels. Current understanding of calcium regulation mechanisms connected to PTH and of the signalling pathways involved derive from in vitro studies carried out on primary c...

  4. HIV Nuclear Entry: Clearing the Fog

    OpenAIRE

    Shah, Vaibhav B.; Christopher Aiken

    2010-01-01

    HIV-1 and other lentiviruses have the unusual capability of infecting nondividing cells, but the mechanism by which they cross an intact nuclear membrane is mysterious. Recent work, including a new study (Lee, K.; Ambrose, Z.; Martin, T.D.; Oztop, I.; Mulky, A.; Julias, J.G.; Vandergraaff, N.; Baumann, J.G.; Wang, R.; Yuen, W. et al. Flexible use of nuclear import pathways by HIV-1. Cell Host Microbe 2010,7, 221-233) confirms that the viral capsid plays a key role in HIV-1 nuclear entry in bo...

  5. Glial calcium signaling in physiology and pathophysioilogy

    Institute of Scientific and Technical Information of China (English)

    Alexei VERKHRASKY

    2006-01-01

    Neuronal-glial circuits underlie integrative processes in the nervous system.Function of glial syncytium is,to a very large extent,regulated by the intracellular calcium signaling system.Glial calcium signals are triggered by activation of multiple receptors,expressed in glial membrane,which regulate both Ca2+ entry and Ca2+ release from the endoplasmic reticulum.The endoplasmic reticulum also endows glial cells with intracellular excitable media,which is able to produce and maintain long-ranging signaling in a form of propagating Ca2+ waves.In pathological conditions,calcium signals regulate glial response to injury,which might have both protective and detrimental effects on the nervous tissue.

  6. Sport entries and qualification manual

    OpenAIRE

    2014-01-01

    This manual is designed to provide National Olympic Committees (NOCs) with the Olympic Sport Entries process, relevant policies, and instructions for completing the online registration for athletes participating in the Sochi 2014 Olympic Winter Games and to assist NOCs in using the online Sport Entries and Qualification (eSEQ) system to complete the entries of their athletes to the Sochi 2014 Olympic Winter Games.

  7. Calcium and Vitamin D

    Science.gov (United States)

    ... Home › Patients › Treatment › Calcium/Vitamin D Calcium/Vitamin D Getting enough calcium and vitamin D is essential ... counter medications and calcium supplements. What is Vitamin D and What Does it Do? Vitamin D plays ...

  8. Entry deterrence and experimentation under demand uncertainty

    OpenAIRE

    Jain, N

    2011-01-01

    We examine the effect of a threat of entry on experimentation about demand by an incumbent monopolist when there is a fixed cost of entry. We show that experimentation may itself be used as a tool for entry deterrence and derive conditions under which experimentation reduces the probability of entry. These conditions depend on the entry rule which in turn depends on entry costs. We show that if experimentation does not deter entry, the monopolist incumbent experiments less. We also characteri...

  9. Importance of Calcium

    OpenAIRE

    TANDOĞAN, Berivan; ULUSU, N. Nuray

    2005-01-01

    Calcium is the most abundant mineral in the body. Calcium regulates many cellular processes and has important structural roles in living organisms. Skeletal muscle structure and function, polymerisation of fibrin and the conduction of impulses in the nervous system are regulated by calcium. Calcium is an important intracellular messenger in protozoa, plants, and animals. Calcium-transporting systems which are located in the plasma membrane and in the organelles, regulate the ionic concentrati...

  10. Store-operated channels regulate intracellular calcium in mammalian rods.

    Science.gov (United States)

    Molnar, Tünde; Barabas, Peter; Birnbaumer, Lutz; Punzo, Claudio; Kefalov, Vladimir; Križaj, David

    2012-08-01

    Exposure to daylight closes cyclic nucleotide-gated (CNG) and voltage-operated Ca(2+) -permeable channels in mammalian rods. The consequent lowering of the cytosolic calcium concentration ([Ca(2+)](i)), if protracted, can contribute to light-induced damage and apoptosis in these cells. We here report that mouse rods are protected against prolonged lowering of [Ca(2+)](i) by store-operated Ca(2+) entry (SOCE). Ca(2+) stores were depleted in Ca(2+)-free saline supplemented with the endoplasmic reticulum (ER) sequestration blocker cyclopiazonic acid. Store depletion elicited [Ca(2+)](i) signals that exceeded baseline [Ca(2+)](i) by 5.9 ± 0.7-fold and were antagonized by an inhibitory cocktail containing 2-APB, SKF 96365 and Gd(3+). Cation influx through SOCE channels was sufficient to elicit a secondary activation of L-type voltage-operated Ca2+ entry. We also found that TRPC1, the type 1 canonical mammalian homologue of the Drosophila photoreceptor TRP channel, is predominantly expressed within the outer nuclear layer of the retina. Rod loss in Pde6b(rdl) (rd1), Chx10/Kip1(-/-rdl) and Elovl4(TG2) dystrophic models was associated with ∼70% reduction in Trpc1 mRNA content whereas Trpc1 mRNA levels in rodless cone-full Nrl(-/-) retinas were decreased by ∼50%. Genetic ablation of TRPC1 channels, however, had no effect on SOCE, the sensitivity of the rod phototransduction cascade or synaptic transmission at rod and cone synapses. Thus, we localized two new mechanisms, SOCE and TRPC1, to mammalian rods and characterized the contribution of SOCE to Ca(2+) homeostasis. By preventing the cytosolic [Ca(2+)](i) from dropping too low under sustained saturating light conditions, these signalling pathways may protect Ca(2+)-dependent mechanisms within the ER and the cytosol without affecting normal rod function. PMID:22674725

  11. Calcium-sensing receptor regulates stomatal closure through hydrogen peroxide and nitric oxide in response to extracellular calcium in Arabidopsis

    OpenAIRE

    Wang, Wen-Hua; Yi, Xiao-Qian; Han, Ai-Dong; Liu, Ting-Wu; Chen, Juan; Wu, Fei-Hua; Dong, Xue-Jun; He, Jun-Xian; Pei, Zhen-Ming; Zheng, Hai-Lei

    2011-01-01

    The Arabidopsis calcium-sensing receptor CAS is a crucial regulator of extracellular calcium-induced stomatal closure. Free cytosolic Ca2+ (Ca2+ i) increases in response to a high extracellular calcium (Ca2+ o) level through a CAS signalling pathway and finally leads to stomatal closure. Multidisciplinary approaches including histochemical, pharmacological, fluorescent, electrochemical, and molecular biological methods were used to discuss the relationship of hydrogen peroxide (H2O2) and nitr...

  12. PDGF-mediated protection of SH-SY5Y cells against Tat toxin involves regulation of extracellular glutamate and intracellular calcium

    International Nuclear Information System (INIS)

    The human immunodeficiency virus (HIV-1) protein Tat has been implicated in mediating neuronal apoptosis, one of the hallmark features of HIV-associated dementia (HAD). Mitigation of the toxic effects of Tat could thus be a potential mechanism for reducing HIV toxicity in the brain. In this study we demonstrated that Tat-induced neurotoxicity was abolished by NMDA antagonist-MK801, suggesting the role of glutamate in this process. Furthermore, we also found that pretreatment of SH-SY5Y cells with PDGF exerted protection against Tat toxicity by decreasing extracellular glutamate levels. We also demonstrated that extracellular calcium chelator EGTA was able to abolish PDGF-mediated neuroprotection, thereby underscoring the role of calcium signaling in PDGF-mediated neuroprotection. We also showed that Erk signaling pathway was critical for PDGF-mediated protection of cells. Additionally, blocking calcium entry with EGTA resulted in suppression of PDGF-induced Erk activation. These findings thus underscore the role of PDGF-mediated calcium signaling and Erk phosphorylation in the protection of cells against HIV Tat toxicity.

  13. Calcium signals and calcium channels in osteoblastic cells

    Science.gov (United States)

    Duncan, R. L.; Akanbi, K. A.; Farach-Carson, M. C.

    1998-01-01

    Calcium (Ca2+) channels are present in non-excitable as well as in excitable cells. In bone cells of the osteoblast lineage, Ca2+ channels play fundamental roles in cellular responses to external stimuli including both mechanical forces and hormonal signals. They are also proposed to modulate paracrine signaling between bone-forming osteoblasts and bone-resorbing osteoclasts at local sites of bone remodeling. Calcium signals are characterized by transient increases in intracellular Ca2+ levels that are associated with activation of intracellular signaling pathways that control cell behavior and phenotype, including patterns of gene expression. Development of Ca2+ signals is a tightly regulated cellular process that involves the concerted actions of plasma membrane and intracellular Ca2+ channels, along with Ca2+ pumps and exchangers. This review summarizes the current state of knowledge concerning the structure, function, and role of Ca2+ channels and Ca2+ signals in bone cells, focusing on the osteoblast.

  14. Membrane associated complexes in calcium dynamics modelling

    International Nuclear Information System (INIS)

    Mitochondria not only govern energy production, but are also involved in crucial cellular signalling processes. They are one of the most important organelles determining the Ca2+ regulatory pathway in the cell. Several mathematical models explaining these mechanisms were constructed, but only few of them describe interplay between calcium concentrations in endoplasmic reticulum (ER), cytoplasm and mitochondria. Experiments measuring calcium concentrations in mitochondria and ER suggested the existence of cytosolic microdomains with locally elevated calcium concentration in the nearest vicinity of the outer mitochondrial membrane. These intermediate physical connections between ER and mitochondria are called MAM (mitochondria-associated ER membrane) complexes. We propose a model with a direct calcium flow from ER to mitochondria, which may be justified by the existence of MAMs, and perform detailed numerical analysis of the effect of this flow on the type and shape of calcium oscillations. The model is partially based on the Marhl et al model. We have numerically found that the stable oscillations exist for a considerable set of parameter values. However, for some parameter sets the oscillations disappear and the trajectories of the model tend to a steady state with very high calcium level in mitochondria. This can be interpreted as an early step in an apoptotic pathway. (paper)

  15. Calcium's Role in Mechanotransduction during Muscle Development

    Directory of Open Access Journals (Sweden)

    Tatiana Benavides Damm

    2014-01-01

    Full Text Available Mechanotransduction is a process where cells sense their surroundings and convert the physical forces in their environment into an appropriate response. Calcium plays a crucial role in the translation of such forces to biochemical signals that control various biological processes fundamental in muscle development. The mechanical stimulation of muscle cells may for example result from stretch, electric and magnetic stimulation, shear stress, and altered gravity exposure. The response, mainly involving changes in intracellular calcium concentration then leads to a cascade of events by the activation of downstream signaling pathways. The key calcium-dependent pathways described here include the nuclear factor of activated T cells (NFAT and mitogen-activated protein kinase (MAPK activation. The subsequent effects in cellular homeostasis consist of cytoskeletal remodeling, cell cycle progression, growth, differentiation, and apoptosis, all necessary for healthy muscle development, repair, and regeneration. A deregulation from the normal process due to disuse, trauma, or disease can result in a clinical condition such as muscle atrophy, which entails a significant loss of muscle mass. In order to develop therapies against such diseased states, we need to better understand the relevance of calcium signaling and the downstream responses to mechanical forces in skeletal muscle. The purpose of this review is to discuss in detail how diverse mechanical stimuli cause changes in calcium homeostasis by affecting membrane channels and the intracellular stores, which in turn regulate multiple pathways that impart these effects and control the fate of muscle tissue.

  16. Transgenic plants with increased calcium stores

    Science.gov (United States)

    Wyatt, Sarah (Inventor); Tsou, Pei-Lan (Inventor); Robertson, Dominique (Inventor); Boss, Wendy (Inventor)

    2004-01-01

    The present invention provides transgenic plants over-expressing a transgene encoding a calcium-binding protein or peptide (CaBP). Preferably, the CaBP is a calcium storage protein and over-expression thereof does not have undue adverse effects on calcium homeostasis or biochemical pathways that are regulated by calcium. In preferred embodiments, the CaBP is calreticulin (CRT) or calsequestrin. In more preferred embodiments, the CaBP is the C-domain of CRT, a fragment of the C-domain, or multimers of the foregoing. In other preferred embodiments, the CaBP is localized to the endoplasmic reticulum by operatively associating the transgene encoding the CaBP with an endoplasmic reticulum localization peptide. Alternatively, the CaBP is targeted to any other sub-cellular compartment that permits the calcium to be stored in a form that is biologically available to the plant. Also provided are methods of producing plants with desirable phenotypic traits by transformation of the plant with a transgene encoding a CaBP. Such phenotypic traits include increased calcium storage, enhanced resistance to calcium-limiting conditions, enhanced growth and viability, increased disease and stress resistance, enhanced flower and fruit production, reduced senescence, and a decreased need for fertilizer production. Further provided are plants with enhanced nutritional value as human food or animal feed.

  17. GOCE Re-Entry Campaign

    Science.gov (United States)

    Bastida, B.; Flohrer, T.; Lemmens, S.; Krag, H.

    2015-03-01

    Every year ESA, through the Space Debris Office, participates to an Inter-Agency Space Debris Coordination Committee (IADC) Re-entry Test Campaign.. For the campaign of 2013, ESA’s proposal to select GOCE's re-entry was accepted. The campaign opened on the 21st October 2013 after fuel depletion of the drag-compensating ion propulsion. GOCE was expected to enter into a phase of attitude-controlled fine-pointing mode (FPM) until the attitude controllers would be unable to cope with the atmospheric torques and then the satellite would enter in a phase of fully uncontrolled flight. In this paper, we present the evolution of ESA’s daily predictions on the re-entry epoch using different sources of orbital information. The uncertainties on the spacecraft operability (i.e. the physical limits of the attitude controller) led to a non-standard re-entry scenario were different attitudes had to be considered (instead of the commonly assumed random tumbling mode case that is used whenever no information on the physical properties of a re-entering object is available). A daily assessment of the status, in coordination with the flight control team, was required and implied a continuous update on the predicted failure point of the attitude controller. This in turn imposed the need for considering an asymmetric re-entry window. These operation-bound uncertainties were simulated to predict the attitude evolution after failure at different altitudes and their effects evaluated to be taken into account for the re-entry predictions. We present ESA’s re-entry prediction activities for GOCE, internally, and within the IADC, and address specific technical aspects and challenges for re-entry predictions, which are related to the expected and occurred attitude of GOCE during the final re-entry phase.

  18. Escape from Human Immunodeficiency Virus Type 1 (HIV-1 Entry Inhibitors

    Directory of Open Access Journals (Sweden)

    Carol D. Weiss

    2012-12-01

    Full Text Available The human immunodeficiency virus (HIV enters cells through a series of molecular interactions between the HIV envelope protein and cellular receptors, thus providing many opportunities to block infection. Entry inhibitors are currently being used in the clinic, and many more are under development. Unfortunately, as is the case for other classes of antiretroviral drugs that target later steps in the viral life cycle, HIV can become resistant to entry inhibitors. In contrast to inhibitors that block viral enzymes in intracellular compartments, entry inhibitors interfere with the function of the highly variable envelope glycoprotein as it continuously adapts to changing immune pressure and available target cells in the extracellular environment. Consequently, pathways and mechanisms of resistance for entry inhibitors are varied and often involve mutations across the envelope gene. This review provides a broad overview of entry inhibitor resistance mechanisms that inform our understanding of HIV entry and the design of new inhibitors and vaccines.

  19. Brownfield Entry in Emerging Markets

    OpenAIRE

    Meyer, Klaus E.; Saul Estrin

    2001-01-01

    This paper focuses on the brown-field entry mode, as a special case of acquisition, in which the resources transferred by the investor dominate over those provided by the acquired firm. We see this mode as having particular relevance for entry strategies in emerging markets. The choice of entry mode is analyzed on the basis of a framework utilizing both resource-based and transaction-cost theories. The resource requirements have to be matched with resources available to the investor through a...

  20. Financial Intermediation and Entry Deterrence

    OpenAIRE

    Jain, Neelam; Thomas D. Jeitschko; Mirman, Leonard J.

    2001-01-01

    In this paper, we analyze the interaction between an incumbent firm's financial contract with abank and its product market decisions in the face of the threat of entry, in a dynamic model.The main results of the paper are: there exists a separating equilibrium with no limit pricing; thelow-cost incumbent repays more to the bank in the first period, due to the threat of entry; andthere are parameter values for which the bank makes more profits with the threat of entry thanwithout.

  1. Entry Threat and Entry Deterrence: The Timing of Broadband Rollout

    OpenAIRE

    Mo Xiao; Orazem, Peter F.

    2007-01-01

    Past empirical literature provides strong evidence that competition increases when new firms enter a market. However, rarely have economists been able to examine how competition changes with the threat of entry. This paper uses the evolution of the zip code level market structure of facilities-based broadband providers from 1999 to 2004 to investigate how a firm adjusts its entry strategy when facing the threat of additional entrants. We identify the potential entrant into a local market as t...

  2. Calcium in diet

    Science.gov (United States)

    ... best source. Milk and dairy products such as yogurt, cheeses, and buttermilk contain a form of calcium ... the amount of calcium in a dairy product. Yogurt, most cheeses, and buttermilk are excellent sources of ...

  3. Fenoprofen calcium overdose

    Science.gov (United States)

    Fenoprofen calcium is a type of medicine called a nonsteroidal anti-inflammatory drug. It is a prescription pain medicine used to relieve symptoms of arthritis . Fenoprofen calcium overdose occurs when someone takes more than the ...

  4. Calcium channel blocker overdose

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/002580.htm Calcium channel blocker overdose To use the sharing features on this page, please enable JavaScript. Calcium channel blockers are a type of medicine used ...

  5. Fenoprofen calcium overdose

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/002649.htm Fenoprofen calcium overdose To use the sharing features on this page, please enable JavaScript. Fenoprofen calcium is a type of medicine called a nonsteroidal ...

  6. Calcium and magnesium disorders.

    Science.gov (United States)

    Goff, Jesse P

    2014-07-01

    Hypocalcemia is a clinical disorder that can be life threatening to the cow (milk fever) and predisposes the animal to various other metabolic and infectious disorders. Calcium homeostasis is mediated primarily by parathyroid hormone, which stimulates bone calcium resorption and renal calcium reabsorption. Parathyroid hormone stimulates the production of 1,25-dihydroxyvitamin D to enhance diet calcium absorption. High dietary cation-anion difference interferes with tissue sensitivity to parathyroid hormone. Hypomagnesemia reduces tissue response to parathyroid hormone. PMID:24980727

  7. 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.

  8. Calcium en cardioplegie

    NARCIS (Netherlands)

    Ruigrok, T.J.C.; Meijler, F.L.

    1985-01-01

    Coronary perfusion with a calcium-free solution, followed by reperfusion with a calcium containing solution, may result in acute myocardial cell death and in irreversible loss of the e1ectrical and mechanical activity of the heart. This phenomenon is known as the calcium paradox. A number of cardiop

  9. Diagram of Calcium Movement in the Human Body

    Science.gov (United States)

    2002-01-01

    This diagram shows the normal pathways of calcium movement in the body and indicates changes (green arrows) seen during preliminary space flight experiments. Calcium plays a central role because 1) it gives strength and structure to bone and 2) all types of cells require it to function normally. To better understand how and why weightlessness induces bone loss, astronauts have participated in a study of calcium kinetics -- that is, the movement of calcium through the body, including absorption from food, and its role in the formation and breakdown of bone.

  10. Reduced calcium-dependent mitochondrial damage underlies the reduced vulnerability of excitotoxicity-tolerant hippocampal neurons.

    Science.gov (United States)

    Pivovarova, Natalia B; Stanika, Ruslan I; Watts, Charlotte A; Brantner, Christine A; Smith, Carolyn L; Andrews, S Brian

    2008-03-01

    In central neurons, over-stimulation of NMDA receptors leads to excessive mitochondrial calcium accumulation and damage, which is a critical step in excitotoxic death. This raises the possibility that low susceptibility to calcium overload-induced mitochondrial damage might characterize excitotoxicity-resistant neurons. In this study, we have exploited two complementary models of preconditioning-induced excitotoxicity resistance to demonstrate reduced calcium-dependent mitochondrial damage in NMDA-tolerant hippocampal neurons. We have further identified adaptations in mitochondrial calcium handling that account for enhanced mitochondrial integrity. In both models, enhanced tolerance was associated with improved preservation of mitochondrial membrane potential and structure. In the first model, which exhibited modest neuroprotection, mitochondria-dependent calcium deregulation was delayed, even though cytosolic and mitochondrial calcium loads were quantitatively unchanged, indicating that enhanced mitochondrial calcium capacity accounts for reduced injury. In contrast, the second model, which exhibited strong neuroprotection, displayed further delayed calcium deregulation and reduced mitochondrial damage because downregulation of NMDA receptor surface expression depressed calcium loading. Reducing calcium entry also modified the chemical composition of the calcium-buffering precipitates that form in calcium-loaded mitochondria. It thus appears that reduced mitochondrial calcium loading is a major factor underlying the robust neuroprotection seen in highly tolerant cells. PMID:18036152

  11. Entry, Descent, Landing Animation (Animation)

    Science.gov (United States)

    2005-01-01

    [figure removed for brevity, see original site] Click on the image for Entry, Descent, Landing animation This animation illustrates the path the Stardust return capsule will follow once it enters Earth's atmosphere.

  12. Tactile Data Entry System Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Building on our successful Phase I Tactile Data Entry program, Barron Associates proposes development of a Glove-Enabled Computer Operations (GECO) system to permit...

  13. Corporate Author Entries. Revision 5

    International Nuclear Information System (INIS)

    This reference authority has been created and is maintained to provide standard forms for recording the names of organizations consistently in bibliographic citations. This revision includes approximately 42,000 entries established since 1973

  14. Orion Entry Handling Qualities Assessments

    Science.gov (United States)

    Bihari, B.; Tiggers, M.; Strahan, A.; Gonzalez, R.; Sullivan, K.; Stephens, J. P.; Hart, J.; Law, H., III; Bilimoria, K.; Bailey, R.

    2011-01-01

    The Orion Command Module (CM) is a capsule designed to bring crew back from the International Space Station (ISS), the moon and beyond. The atmospheric entry portion of the flight is deigned to be flown in autopilot mode for nominal situations. However, there exists the possibility for the crew to take over manual control in off-nominal situations. In these instances, the spacecraft must meet specific handling qualities criteria. To address these criteria two separate assessments of the Orion CM s entry Handling Qualities (HQ) were conducted at NASA s Johnson Space Center (JSC) using the Cooper-Harper scale (Cooper & Harper, 1969). These assessments were conducted in the summers of 2008 and 2010 using the Advanced NASA Technology Architecture for Exploration Studies (ANTARES) six degree of freedom, high fidelity Guidance, Navigation, and Control (GN&C) simulation. This paper will address the specifics of the handling qualities criteria, the vehicle configuration, the scenarios flown, the simulation background and setup, crew interfaces and displays, piloting techniques, ratings and crew comments, pre- and post-fight briefings, lessons learned and changes made to improve the overall system performance. The data collection tools, methods, data reduction and output reports will also be discussed. The objective of the 2008 entry HQ assessment was to evaluate the handling qualities of the CM during a lunar skip return. A lunar skip entry case was selected because it was considered the most demanding of all bank control scenarios. Even though skip entry is not planned to be flown manually, it was hypothesized that if a pilot could fly the harder skip entry case, then they could also fly a simpler loads managed or ballistic (constant bank rate command) entry scenario. In addition, with the evaluation set-up of multiple tasks within the entry case, handling qualities ratings collected in the evaluation could be used to assess other scenarios such as the constant bank angle

  15. Stackelberg competition with endogenous entry

    OpenAIRE

    Etro, F.

    2007-01-01

    This paper analyzes market structures where leaders have a first mover advantage and entry by the followers is endogenous. The strategy of the leaders is always more aggressive than the strategy of the followers independently from strategic substitutability or complementarity. Under quantity competition, the leader produces more than any other firm and I determine the conditions for entry deterrence to be optimal (high substitutability and constant or decreasing marginal costs). Under price c...

  16. Autonomous gliding entry guidance with

    OpenAIRE

    Guo Jie; Wu Xuzhong; Tang Shengjing

    2015-01-01

    This paper presents a novel three-dimensional autonomous entry guidance for relatively high lift-to-drag ratio vehicles satisfying geographic constraints and other path constraints. The guidance is composed of onboard trajectory planning and robust trajectory tracking. For trajectory planning, a longitudinal sub-planner is introduced to generate a feasible drag-versus-energy profile by using the interpolation between upper boundary and lower boundary of entry corridor to get the desired traje...

  17. Network Competition and Entry Deterrence

    OpenAIRE

    Calzada, Joan; Valletti, Tommaso

    2005-01-01

    We develop a model of logit demand that extends to a multi-firm industry the traditional duopoly framework of network competition with access charges. Firstly, we show that, when incumbents do not face the threat of entry and compete in prices, they inefficiently establish the reciprocal access charge below cost. This inefficiency disappears if incumbents compete in utilities instead of prices. Secondly, we study how incumbents change their choices under the threat of entry when they determin...

  18. Re-entry flight clearance

    OpenAIRE

    Juliana, S.

    2006-01-01

    The objective of the research was to identify and evaluate promising mathematical techniques for re-entry flight clearance. To fulfil this objective, two mathematical methods were investigated and developed: μ analysis for linear models and interval analysis for both linear and non-linear models. The stability of re-entry vehicles in the presence of model uncertainties was chosen as the clearance criterion, which is represented by two mathematical criteria: worst-case eigenvalues (linear...

  19. Calcium regulates caveolin-1 expression at the transcriptional level

    International Nuclear Information System (INIS)

    Highlights: ► Caveolin-1 expression is regulated by calcium signaling at the transcriptional level. ► An inhibitor of or siRNA to L-type calcium channel suppressed caveolin-1 expression. ► Cyclosporine A or an NFAT inhibitor markedly reduced caveolin-1 expression. ► Caveolin-1 regulation by calcium signaling is observed in several mouse cell lines. -- Abstract: Caveolin-1, an indispensable component of caveolae serving as a transformation suppressor protein, is highly expressed in poorly metastatic mouse osteosarcoma FBJ-S1 cells while highly metastatic FBJ-LL cells express low levels of caveolin-1. Calcium concentration is higher in FBJ-S1 cells than in FBJ-LL cells; therefore, we investigated the possibility that calcium signaling positively regulates caveolin-1 in mouse FBJ-S1 cells. When cells were treated with the calcium channel blocker nifedipine, cyclosporin A (a calcineurin inhibitor), or INCA-6 (a nuclear factor of activated T-cells [NFAT] inhibitor), caveolin-1 expression at the mRNA and protein levels decreased. RNA silencing of voltage-dependent L-type calcium channel subunit alpha-1C resulted in suppression of caveolin-1 expression. This novel caveolin-1 regulation pathway was also identified in mouse NIH 3T3 cells and Lewis lung carcinoma cells. These results indicate that caveolin-1 is positively regulated at the transcriptional level through a novel calcium signaling pathway mediated by L-type calcium channel/Ca2+/calcineurin/NFAT.

  20. Productive Entry of Foot-and-Mouth Disease Virus via Macropinocytosis Independent of Phosphatidylinositol 3-Kinase.

    Science.gov (United States)

    Han, Shi-Chong; Guo, Hui-Chen; Sun, Shi-Qi; Jin, Ye; Wei, Yan-Quan; Feng, Xia; Yao, Xue-Ping; Cao, Sui-Zhong; Xiang Liu, Ding; Liu, Xiang-Tao

    2016-01-01

    Virus entry is an attractive target for therapeutic intervention. Here, using a combination of electron microscopy, immunofluorescence assay, siRNA interference, specific pharmacological inhibitors, and dominant negative mutation, we demonstrated that the entry of foot-and-mouth disease virus (FMDV) triggered a substantial amount of plasma membrane ruffling. We also found that the internalization of FMDV induced a robust increase in fluid-phase uptake, and virions internalized within macropinosomes colocalized with phase uptake marker dextran. During this stage, the Rac1-Pak1 signaling pathway was activated. After specific inhibition on actin, Na(+)/H(+) exchanger, receptor tyrosine kinase, Rac1, Pak1, myosin II, and protein kinase C, the entry and infection of FMDV significantly decreased. However, inhibition of phosphatidylinositol 3-kinase (PI3K) did not reduce FMDV internalization but increased the viral entry and infection to a certain extent, implying that FMDV entry did not require PI3K activity. Results showed that internalization of FMDV exhibited the main hallmarks of macropinocytosis. Moreover, intracellular trafficking of FMDV involves EEA1/Rab5-positive vesicles. The present study demonstrated macropinocytosis as another endocytic pathway apart from the clathrin-mediated pathway. The findings greatly expand our understanding of the molecular mechanisms of FMDV entry into cells, as well as provide potential insights into the entry mechanisms of other picornaviruses. PMID:26757826

  1. 19 CFR 142.16 - Entry summary documentation.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 2 2010-04-01 2010-04-01 false Entry summary documentation. 142.16 Section 142.16... TREASURY (CONTINUED) ENTRY PROCESS Entry Summary Documentation § 142.16 Entry summary documentation. (a) Entry summary not filed at time of entry. When the entry documentation is filed before the entry...

  2. Neural stem cell-derived exosomes mediate viral entry

    Directory of Open Access Journals (Sweden)

    Sims B

    2014-10-01

    Full Text Available Brian Sims,1,2,* Linlin Gu,3,* Alexandre Krendelchtchikov,3 Qiana L Matthews3,4 1Division of Neonatology, Department of Pediatrics, 2Department of Cell, Developmental, and Integrative Biology, 3Division of Infectious Diseases, Department of Medicine, 4Center for AIDS Research, University of Alabama at Birmingham, Birmingham, AL, USA *These authors contributed equally to this work Background: Viruses enter host cells through interactions of viral ligands with cellular receptors. Viruses can also enter cells in a receptor-independent fashion. Mechanisms regarding the receptor-independent viral entry into cells have not been fully elucidated. Exosomal trafficking between cells may offer a mechanism by which viruses can enter cells.Methods: To investigate the role of exosomes on cellular viral entry, we employed neural stem cell-derived exosomes and adenovirus type 5 (Ad5 for the proof-of-principle study. Results: Exosomes significantly enhanced Ad5 entry in Coxsackie virus and adenovirus receptor (CAR-deficient cells, in which Ad5 only had very limited entry. The exosomes were shown to contain T-cell immunoglobulin mucin protein 4 (TIM-4, which binds phosphatidylserine. Treatment with anti-TIM-4 antibody significantly blocked the exosome-mediated Ad5 entry.Conclusion: Neural stem cell-derived exosomes mediated significant cellular entry of Ad5 in a receptor-independent fashion. This mediation may be hampered by an antibody specifically targeting TIM-4 on exosomes. This set of results will benefit further elucidation of virus/exosome pathways, which would contribute to reducing natural viral infection by developing therapeutic agents or vaccines. Keywords: neural stem cell-derived exosomes, adenovirus type 5, TIM-4, viral entry, phospholipids

  3. Dopamine receptor activation increases HIV entry into primary human macrophages.

    Directory of Open Access Journals (Sweden)

    Peter J Gaskill

    Full Text Available Macrophages are the primary cell type infected with HIV in the central nervous system, and infection of these cells is a major component in the development of neuropathogenesis and HIV-associated neurocognitive disorders. Within the brains of drug abusers, macrophages are exposed to increased levels of dopamine, a neurotransmitter that mediates the addictive and reinforcing effects of drugs of abuse such as cocaine and methamphetamine. In this study we examined the effects of dopamine on HIV entry into primary human macrophages. Exposure to dopamine during infection increased the entry of R5 tropic HIV into macrophages, irrespective of the concentration of the viral inoculum. The entry pathway affected was CCR5 dependent, as antagonizing CCR5 with the small molecule inhibitor TAK779 completely blocked entry. The effect was dose-dependent and had a steep threshold, only occurring above 108 M dopamine. The dopamine-mediated increase in entry required dopamine receptor activation, as it was abrogated by the pan-dopamine receptor antagonist flupenthixol, and could be mediated through both subtypes of dopamine receptors. These findings indicate that the effects of dopamine on macrophages may have a significant impact on HIV pathogenesis. They also suggest that drug-induced increases in CNS dopamine may be a common mechanism by which drugs of abuse with distinct modes of action exacerbate neuroinflammation and contribute to HIV-associated neurocognitive disorders in infected drug abusers.

  4. CCN3 and calcium signaling

    Directory of Open Access Journals (Sweden)

    Li Chang Long

    2003-08-01

    Full Text Available Abstract The CCN family of genes consists presently of six members in human (CCN1-6 also known as Cyr61 (Cystein rich 61, CTGF (Connective Tissue Growth Factor, NOV (Nephroblastoma Overexpressed gene, WISP-1, 2 and 3 (Wnt-1 Induced Secreted Proteins. Results obtained over the past decade have indicated that CCN proteins are matricellular proteins, which are involved in the regulation of various cellular functions, such as proliferation, differentiation, survival, adhesion and migration. The CCN proteins have recently emerged as regulatory factors involved in both internal and external cell signaling. CCN3 was reported to physically interact with fibulin-1C, integrins, Notch and S100A4. Considering that, the conformation and biological activity of these proteins are dependent upon calcium binding, we hypothesized that CCN3 might be involved in signaling pathways mediated by calcium ions. In this article, we review the data showing that CCN3 regulates the levels of intracellular calcium and discuss potential models that may account for the biological effects of CCN3.

  5. HIV Nuclear Entry: Clearing the Fog.

    Science.gov (United States)

    Shah, Vaibhav B; Aiken, Christopher

    2010-05-01

    HIV-1 and other lentiviruses have the unusual capability of infecting nondividing cells, but the mechanism by which they cross an intact nuclear membrane is mysterious. Recent work, including a new study (Lee, K.; Ambrose, Z.; Martin, T.D.; Oztop, I.; Mulky, A.; Julias, J.G.; Vandergraaff, N.; Baumann, J.G.; Wang, R.; Yuen, W. et al. Flexible use of nuclear import pathways by HIV-1. Cell Host Microbe2010, 7, 221-233) confirms that the viral capsid plays a key role in HIV-1 nuclear entry in both dividing and nondividing cells. The identification of mutations in the viral capsid that alter the virus's dependence on host cell nucleoporins represents an important advance in this poorly understood stage of the virus life cycle. PMID:21994675

  6. HIV Nuclear Entry: Clearing the Fog

    Directory of Open Access Journals (Sweden)

    Vaibhav B. Shah

    2010-05-01

    Full Text Available HIV-1 and other lentiviruses have the unusual capability of infecting nondividing cells, but the mechanism by which they cross an intact nuclear membrane is mysterious. Recent work, including a new study (Lee, K.; Ambrose, Z.; Martin, T.D.; Oztop, I.; Mulky, A.; Julias, J.G.; Vandergraaff, N.; Baumann, J.G.; Wang, R.; Yuen, W. et al. Flexible use of nuclear import pathways by HIV-1. Cell Host Microbe 2010,7, 221-233 confirms that the viral capsid plays a key role in HIV-1 nuclear entry in both dividing and nondividing cells. The identification of mutations in the viral capsid that alter the virus’s dependence on host cell nucleoporins represents an important advance in this poorly understood stage of the virus life cycle.

  7. HIV Nuclear Entry: Clearing the Fog

    Science.gov (United States)

    Shah, Vaibhav B.; Aiken, Christopher

    2010-01-01

    HIV-1 and other lentiviruses have the unusual capability of infecting nondividing cells, but the mechanism by which they cross an intact nuclear membrane is mysterious. Recent work, including a new study (Lee, K.; Ambrose, Z.; Martin, T.D.; Oztop, I.; Mulky, A.; Julias, J.G.; Vandergraaff, N.; Baumann, J.G.; Wang, R.; Yuen, W. et al. Flexible use of nuclear import pathways by HIV-1. Cell Host Microbe 2010, 7, 221–233) confirms that the viral capsid plays a key role in HIV-1 nuclear entry in both dividing and nondividing cells. The identification of mutations in the viral capsid that alter the virus’s dependence on host cell nucleoporins represents an important advance in this poorly understood stage of the virus life cycle. PMID:21994675

  8. Entry Mode Choice of Multinational Banks

    OpenAIRE

    Lehner, Maria

    2008-01-01

    When expanding abroad, a multinational bank faces a trade-off between accessing a foreign country via cross border lending or a financial foreign direct investment, i.e. greenfield or acquisition entry. We analyze the entry mode choice of multinational banks and explicitly derive the entry mode pattern in the banking industry. Moreover, we show that in less developed banking markets, a trend towards cross border lending and acquisition entry exists. Greenfield entry prevails in more developed...

  9. The Timothy syndrome mutation differentially affects voltage- and calcium-dependent inactivation of CaV1.2 L-type calcium channels

    OpenAIRE

    Barrett, Curtis F.; Tsien, Richard W.

    2008-01-01

    Calcium entry into excitable cells is an important physiological signal, supported by and highly sensitive to the activity of voltage-gated Ca2+ channels. After membrane depolarization, Ca2+ channels first open but then undergo various forms of negative feedback regulation including voltage- and calcium-dependent inactivation (VDI and CDI, respectively). Inactivation of Ca2+ channel activity is perturbed in a rare yet devastating disorder known as Timothy syndrome (TS), whose features include...

  10. Expression patterns of intestinal calcium transport factors and ex-vivo absorption of calcium in horses

    OpenAIRE

    Sprekeler Nele; Müller Tobias; Kowalewski Mariusz P; Liesegang Annette; Boos Alois

    2011-01-01

    Abstract Background In many species, the small intestine is the major site of calcium (Ca2+) absorption. The horse differs considerably from most other species with regard to the physiology of its Ca2+ metabolism and digestion. Thus, this study was performed to get more information about the transcellular Ca2+ absorption in the horse. Two mechanisms of intestinal Ca2+ absorption are described: the passive paracellular pathway and the active, vitamin D-dependent transcellular pathway. The latt...

  11. Autonomous gliding entry guidance with

    Directory of Open Access Journals (Sweden)

    Guo Jie

    2015-10-01

    Full Text Available This paper presents a novel three-dimensional autonomous entry guidance for relatively high lift-to-drag ratio vehicles satisfying geographic constraints and other path constraints. The guidance is composed of onboard trajectory planning and robust trajectory tracking. For trajectory planning, a longitudinal sub-planner is introduced to generate a feasible drag-versus-energy profile by using the interpolation between upper boundary and lower boundary of entry corridor to get the desired trajectory length. The associated magnitude of the bank angle can be specified by drag profile, while the sign of bank angle is determined by lateral sub-planner. Two-reverse mode is utilized to satisfy waypoint constraints and dynamic heading error corridor is utilized to satisfy no-fly zone constraints. The longitudinal and lateral sub-planners are iteratively employed until all of the path constraints are satisfied. For trajectory tracking, a novel tracking law based on the active disturbance rejection control is introduced. Finally, adaptability tests and Monte Carlo simulations of the entry guidance approach are performed. Results show that the proposed entry guidance approach can adapt to different entry missions and is able to make the vehicle reach the prescribed target point precisely in spite of geographic constraints.

  12. Calcium absorption and achlorhydria

    International Nuclear Information System (INIS)

    Defective absorption of calcium has been thought to exist in patients with achlorhydria. The author compared absorption of calcium in its carbonate form with that in a pH-adjusted citrate form in a group of 11 fasting patients with achlorhydria and in 9 fasting normal subjects. Fractional calcium absorption was measured by a modified double-isotope procedure with 0.25 g of calcium used as the carrier. Mean calcium absorption (+/- S.D.) in the patients with achlorhydria was 0.452 +/- 0.125 for citrate and 0.042 +/- 0.021 for carbonate (P less than 0.0001). Fractional calcium absorption in the normal subjects was 0.243 +/- 0.049 for citrate and 0.225 +/- 0.108 for carbonate (not significant). Absorption of calcium from carbonate in patients with achlorhydria was significantly lower than in the normal subjects and was lower than absorption from citrate in either group; absorption from citrate in those with achlorhydria was significantly higher than in the normal subjects, as well as higher than absorption from carbonate in either group. Administration of calcium carbonate as part of a normal breakfast resulted in completely normal absorption in the achlorhydric subjects. These results indicate that calcium absorption from carbonate is impaired in achlorhydria under fasting conditions. Since achlorhydria is common in older persons, calcium carbonate may not be the ideal dietary supplement

  13. EXERCISE ENHANCING CALCIUM ABSORPTION MECHANISM

    OpenAIRE

    Muliani

    2013-01-01

    Calcium has important role in many biological processes therefore calcium homeostasis should be maintained. Imbalance in calcium homeostasis would affects the bone metabolism, neuromuscular function, blood coagulation, cell proliferation and signal transduction. Homeostasis of calcium is maintained by three major organs: gastrointestinal tract, bone and kidney. Intestinal calcium absorption is the sole mechanism to supply calcium to the body. Calcium absorption controlled by calcitropic hormo...

  14. Dengue and Calcium

    OpenAIRE

    Shivanthan, Mitrakrishnan C; Rajapakse, Senaka

    2014-01-01

    Dengue is potentially fatal unless managed appropriately. No specific treatment is available and the mainstay of treatment is fluid management with careful monitoring, organ support, and correction of metabolic derangement. Evidence with regards to the role of calcium homeostasis in dengue is limited. Low blood calcium levels have been demonstrated in dengue infection and hypocalcemia maybe more pronounced in more severe forms. The cause of hypocalcemia is likely to be multifactorial. Calcium...

  15. Measurements of intracellular calcium

    International Nuclear Information System (INIS)

    Intracellular calcium concentration ([Ca2+]i) has been measured in cultured cells by using Fura-2 load cells and a computer-controlled Perkin Elmer LS-5B spectrofluorometer. Increased [Ca2+]i in cells exposed to extracellular bilirubin was observed both with and without extracellular calcium. However, the increase was considerable larger with extracellular calcium. The enhancement of [Ca2+]i became smaller with decreasing bilirubin/BSA (bovine serum albumine) ratio. 5 refs., 5 figs

  16. Partitioning of 222Rn entry into a structure surrounded by soil

    International Nuclear Information System (INIS)

    This paper describes the entry rate of 222Rn into a basement structure surrounded by a sandy clay loam soil. The highest indoor radon concentrations occurred when the rate of entry was lowest. Data from in-situ measurements were used to identify the entry pathways and also the origins of the radon during periods when the entry rate was low. Results indicated that 25% of the radon entered through the floor-wall joint and 75% through the floor and walls. About 30% of the radon originated in the concrete. Diffusion was the primary transport mechanism. However, radon entry through the floor-wall joint was a combination of diffusion and a convective flow between the subslab region and the interior of the structure. 18 refs., 7 figs., 4 tabs

  17. Duration differences of corticostriatal responses in striatal projection neurons depend on calcium activated potassium currents

    Directory of Open Access Journals (Sweden)

    Mario Alberto Arias-García

    2013-10-01

    Full Text Available The firing of striatal projection neurons (SPNs exhibits afterhyperpolarizing potentials (AHPs that determine discharge frequency. They are in part generated by Ca2+-activated K+-currents involving BK and SK components. It has previously been shown that suprathreshold corticostriatal responses are more prolonged and evoke more action potentials in direct pathway SPNs (dSPNs than in indirect pathway SPNs (iSPNs. In contrast, iSPNs generate dendritic autoregenerative responses. Using whole cell recordings in brain slices, we asked whether the participation of Ca2+-activated K+-currents plays a role in these responses. Secondly, we asked if these currents may explain some differences in synaptic integration between dSPNs and iSPNs. Neurons obtained from BAC D1 and D2 GFP mice were recorded. We used charybdotoxin and apamin to block BK and SK channels, respectively. Both antagonists increased the depolarization and delayed the repolarization of suprathreshold corticostriatal responses in both neuron classes. We also used NS 1619 and NS 309 (CyPPA, to enhance BK and SK channels, respectively. Current enhancers hyperpolarized and accelerated the repolarization of corticostriatal responses in both neuron classes. These drugs made evident that the contribution of Ca2+-activated K+-currents was different in dSPNs as compared to iSPNs: in dSPNs their activation was slower as though calcium took a diffusion delay to activate them. In contrast, their activation was fast and then sustained in iSPNs as though calcium flux activates them at the moment of entry. The blockade of Ca2+-activated K+-currents made iSPNs to look as dSPNs. Conversely, their enhancement made dSPNs to look as iSPNs. It is concluded that Ca2+-activated K+-currents are a main intrinsic determinant causing the differences in synaptic integration between corticostriatal polysynaptic responses between dSPNs and iSPNs.

  18. Auranofin, an Anti-Rheumatic Gold Compound, Modulates Apoptosis by Elevating the Intracellular Calcium Concentration ([Ca{sup 2+}]{sub i}) in MCF-7 Breast Cancer Cells

    Energy Technology Data Exchange (ETDEWEB)

    Varghese, Elizabeth; Büsselberg, Dietrich, E-mail: dib2015@qatar-med.cornell.edu [Weil Cornell Medical College in Qatar, Qatar Foundation-Education City, P.O. Box 24144 Doha (Qatar)

    2014-11-06

    Auranofin, a transition metal complex is used for the treatment of rheumatoid arthritis but is also an effective anti-cancer drug. We investigate the effects of Auranofin in inducing cell death by apoptosis and whether these changes are correlated to changes of intracellular calcium concentration ([Ca{sup 2+}]{sub i}) in breast cancer cells (MCF-7). Cytotoxicity of Auranofin was evaluated using MTS assay and the Trypan blue dye exclusion method. With fluorescent dyes SR-FLICA and 7-AAD apoptotic death and necrotic death were differentiated by Flow cytometry. A concentration dependent decrease in the viability occurred and cells were shifted to the apoptotic phase. Intracellular calcium ([Ca{sup 2+}]{sub i}) was recorded using florescence microscopy and a calcium sensitive dye (Fluo-4 AM) with a strong negative correlation (r = −0.713) to viability. Pharmacological modulators 2-APB (50 μM), Nimodipine (10 μM), Caffeine (10 mM), SKF 96365(20 μM) were used to modify calcium entry and release. Auranofin induced a sustained increase of [Ca{sup 2+}]{sub i} in a concentration and time dependent manner. The use of different blockers of calcium channels did not reveal the source for the rise of [Ca{sup 2+}]{sub i}. Overall, elevation of [Ca{sup 2+}]{sub i} by Auranofin might be crucial for triggering Ca{sup 2+}-dependent apoptotic pathways. Therefore, in anti-cancer therapy, modulating [Ca{sup 2+}]{sub i} should be considered as a crucial factor for the induction of cell death in cancer cells.

  19. The pace of MNEs’ sequential entries: Cumulative entry experience and the dynamic process

    OpenAIRE

    Gerald Yong Gao; Yigang Pan

    2010-01-01

    This study examines the pace with which multinational enterprises undertake sequential entries in a foreign market. We focus on learning effects from cumulative entry experience of different modes within a host market. Moreover, we investigate the dynamic process of entry mode switch, and how cumulative entry experience reduces the expansion constraint. Using a dataset of sequential entries by US firms in China during 1979–2002, we find that the impact of cumulative entry experience on the pa...

  20. Human SCARB2-mediated entry and endocytosis of EV71.

    Directory of Open Access Journals (Sweden)

    Yi-Wen Lin

    Full Text Available Enterovirus (EV 71 infection is known to cause hand-foot-and-mouth disease (HFMD and in severe cases, induces neurological disorders culminating in fatality. An outbreak of EV71 in South East Asia in 1997 affected over 120,000 people and caused neurological disorders in a few individuals. The control of EV71 infection through public health interventions remains minimal and treatments are only symptomatic. Recently, human scavenger receptor class B, member 2 (SCARB2 has been reported to be a cellular receptor of EV71. We expressed human SCARB2 gene in NIH3T3 cells (3T3-SCARB2 to study the mechanisms of EV71 entry and infection. We demonstrated that human SCARB2 serves as a cellular receptor for EV71 entry. Disruption of expression of SCARB2 using siRNAs can interfere EV71 infection and subsequent inhibit the expression of viral capsid proteins in RD and 3T3-SCARB2 but not Vero cells. SiRNAs specific to clathrin or dynamin or chemical inhibitor of clathrin-mediated endocytosis were all capable of interfering with the entry of EV71 into 3T3-SCARB2 cells. On the other hand, caveolin specific siRNA or inhibitors of caveolae-mediated endocytosis had no effect, confirming that only clathrin-mediated pathway was involved in EV71 infection. Endocytosis of EV71 was also found to be pH-dependent requiring endosomal acidification and also required intact membrane cholesterol. In summary, the mechanism of EV71 entry through SCARB2 as the receptor for attachment, and its cellular entry is through a clathrin-mediated and pH-dependent endocytic pathway. This study on the receptor and endocytic mechanisms of EV71 infection is useful for the development of effective medications and prophylactic treatment against the enterovirus.

  1. Simultaneous analysis of large-scale RNAi screens for pathogen entry

    OpenAIRE

    Rämö, Pauli; Drewek, Anna; Arrieumerlou, Cécile; Beerenwinkel, Niko; Ben-Tekaya, Houchaima; Cardel, Bettina; Casanova, Alain; Conde-Alvarez, Raquel; Cossart, Pascale; Csúcs, Gábor; Eicher, Simone; Emmenlauer, Mario; Greber, Urs; Hardt, Wolf-Dietrich; Helenius, Ari

    2014-01-01

    Background Large-scale RNAi screening has become an important technology for identifying genes involved in biological processes of interest. However, the quality of large-scale RNAi screening is often deteriorated by off-targets effects. In order to find statistically significant effector genes for pathogen entry, we systematically analyzed entry pathways in human host cells for eight pathogens using image-based kinome-wide siRNA screens with siRNAs from three vendors. We propose a Parallel M...

  2. Poxvirus entry and membrane fusion

    International Nuclear Information System (INIS)

    The study of poxvirus entry and membrane fusion has been invigorated by new biochemical and microscopic findings that lead to the following conclusions: (1) the surface of the mature virion (MV), whether isolated from an infected cell or by disruption of the membrane wrapper of an extracellular virion, is comprised of a single lipid membrane embedded with non-glycosylated viral proteins; (2) the MV membrane fuses with the cell membrane, allowing the core to enter the cytoplasm and initiate gene expression; (3) fusion is mediated by a newly recognized group of viral protein components of the MV membrane, which are conserved in all members of the poxvirus family; (4) the latter MV entry/fusion proteins are required for cell to cell spread necessitating the disruption of the membrane wrapper of extracellular virions prior to fusion; and furthermore (5) the same group of MV entry/fusion proteins are required for virus-induced cell-cell fusion. Future research priorities include delineation of the roles of individual entry/fusion proteins and identification of cell receptors

  3. Delayed School Entry in Uganda

    Science.gov (United States)

    Moyi, Peter

    2011-01-01

    Since 1997 Uganda has seen a large increase in school enrolment. Despite this increased enrolment, universal education has remained elusive. Many children enrol in school, but not at the recommended age, and they drop out before completing school. This article focuses on one of these problems--delayed school entry. What household factors are…

  4. Calcium D-saccharate

    DEFF Research Database (Denmark)

    Garcia, André Castilho; Hedegaard, Martina Vavrusova; Skibsted, Leif Horsfelt

    2016-01-01

    Molar conductivity of saturated aqueous solutions of calcium d-saccharate, used as a stabilizer of beverages fortified with calcium d-gluconate, increases strongly upon dilution, indicating complex formation between calcium and d-saccharate ions, for which, at 25 °C, Kassoc = 1032 ± 80, ΔHassoc......° = -34 ± 6 kJ mol-1, and ΔSassoc° = -55 ± 9 J mol-1 K-1, were determined electrochemically. Calcium d-saccharate is sparingly soluble, with a solubility product, Ksp, of (6.17 ± 0.32) × 10-7 at 25 °C, only moderately increasing with the temperature: ΔHsol° = 48 ± 2 kJ mol-1, and ΔSassoc° = 42 ± 7 J mol-1...... K-1. Equilibria in supersaturated solutions of calcium d-saccharate seem only to adjust slowly, as seen from calcium activity measurements in calcium d-saccharate solutions made supersaturated by cooling. Solutions formed by isothermal dissolution of calcium d-gluconate in aqueous potassium d...

  5. Serum Calcium Level in Hypertension

    OpenAIRE

    Hazari, Mohammed Abdul Hannan; Arifuddin, Mehnaaz Sameera; Muzzakar, Syed; Reddy, Vontela Devender

    2012-01-01

    Background: The alterations in extracellular calcium level may influence intracellular calcium level and possibly play a role in the pathogenesis of essential hypertension. Aim: The purpose was to find out the association between serum calcium levels and hypertension; and to compare the serum calcium levels between normotensive controls, hypertensive subjects on calcium channel blockers, and hypertensive subjects on antihypertensive medication other than calcium channel blockers. Materials an...

  6. Bi-weekly waterfowl survey data entry

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — Data sheet for the entry of bi-weekly waterfowl survey data from the state of Kansas. This Excel file contains the data entry sheet and a chart displaying waterfowl...

  7. Venezuelan equine encephalitis virus entry mechanism requires late endosome formation and resists cell membrane cholesterol depletion

    International Nuclear Information System (INIS)

    Virus envelope proteins determine receptor utilization and host range. The choice of receptor not only permits specific targeting of cells that express it, but also directs the virus into specific endosomal trafficking pathways. Disrupting trafficking can result in loss of virus infectivity due to redirection of virions to non-productive pathways. Identification of the pathway or pathways used by a virus is, thus, important in understanding virus pathogenesis mechanisms and for developing new treatment strategies. Most of our understanding of alphavirus entry has focused on the Old World alphaviruses, such as Sindbis and Semliki Forest virus. In comparison, very little is known about the entry route taken by more pathogenic New World alphaviruses. Here, we use a novel contents mixing assay to identify the cellular requirements for entry of a New World alphavirus, Venezuelan equine encephalitis virus (VEEV). Expression of dominant negative forms of key endosomal trafficking genes shows that VEEV must access clathrin-dependent endocytic vesicles for membrane fusion to occur. Unexpectedly, the exit point is different from Old World alphaviruses that leave from early endosomes. Instead, VEEV also requires functional late endosomes. Furthermore, unlike the Old World viruses, VEEV entry is insensitive to cholesterol sequestration from cell membranes and may reflect a need to access an endocytic compartment that lacks cholesterol. This indicates fundamental differences in the entry route taken by VEEV compared to Old World alphaviruses

  8. Sunk Costs and Antitrust Barriers to Entry

    OpenAIRE

    SCHMALENSEE, Richard

    2004-01-01

    US antitrust policy takes as its objective consumer welfare, not total economic welfare. With that objective, Joe Bain's definition of entry barriers is more useful than George Stigler's or definitions based on economic welfare. It follows that economies of scale that involve sunk costs may create antitrust barriers to entry. A simple model shows that sunk costs without scale economies may discourage entry without creating an antitrust entry barrier.

  9. Predicting the Diversity of Foreign Entry Modes

    OpenAIRE

    Hashai, Niron; Asmussen, Christian G.; Benito, Gabriel R. G.; Petersen, Bent

    2007-01-01

    This paper expands entry mode literature by referring to multiple modes exerted in different value chain activities within and across host markets, rather than to a single entry mode at the host market level. Scale of operations and knowledge intensity are argued to affect firms’ entry mode diversity across value chain activities and host markets. Analyzing a sample of Israeli based firms we show that larger firms exhibit a higher degree of entry mode diversity both across value chain activit...

  10. Endogenous Market Structure and Foreign Market Entry

    OpenAIRE

    Markusen, James R.; Frank Stähler

    2009-01-01

    Models dealing with cross-border acquisitions versus greenfield investment usually assume that the entry of a foreign firm into a market has effects on the outputs of all domestic firms in that market, but exit or entry of local firms is not considered. The purpose of this paper is to re-examine the acquisition versus greenfield versus exporting question under fixed versus free entry assumptions for local firms. Our finding is that greenfield entry and exporting options are more attractive re...

  11. HYPERTHERMIA, INTRACELLULAR FREE CALCIUM AND CALCIUM IONOPHORES

    NARCIS (Netherlands)

    STEGE, GJJ; WIERENGA, PK; KAMPINGA, HH; KONINGS, AWT

    1993-01-01

    It is shown that heat-induced increase of intracellular calcium does not correlate with hyperthermic cell killing. Six different cell lines were investigated; in four (EAT, HeLa S3, L5178Y-R and L5178Y-S) heat treatments killing 90% of the cells did not affect the levels of intracellular free calciu

  12. Limonin, a Component of Dictamni Radicis Cortex, Inhibits Eugenol-Induced Calcium and cAMP Levels and PKA/CREB Signaling Pathway in Non-Neuronal 3T3-L1 Cells

    Directory of Open Access Journals (Sweden)

    Yeo Cho Yoon

    2015-12-01

    Full Text Available Limonin, one of the major components in dictamni radicis cortex (DRC, has been shown to play various biological roles in cancer, inflammation, and obesity in many different cell types and tissues. Recently, the odorant-induced signal transduction pathway (OST has gained attention not only because of its function in the perception of smell but also because of its numerous physiological functions in non-neuronal cells. However, little is known about the effects of limonin and DRC on the OST pathway in non-neuronal cells. We investigated odorant-stimulated increases in Ca2+ and cAMP, major second messengers in the OST pathway, in non-neuronal 3T3-L1 cells pretreated with limonin and ethanol extracts of DRC. Limonin and the extracts significantly decreased eugenol-induced Ca2+ and cAMP levels and upregulated phosphorylation of CREB and PKA. Our results demonstrated that limonin and DRC extract inhibit the OST pathway in non-neuronal cells by modulating Ca2+ and cAMP levels and phosphorylation of CREB.

  13. Calmidazolium evokes high calcium fluctuations in Plasmodium falciparum.

    Science.gov (United States)

    Budu, Alexandre; Gomes, Mayrim M; Melo, Pollyana M; El Chamy Maluf, Sarah; Bagnaresi, Piero; Azevedo, Mauro F; Carmona, Adriana K; Gazarini, Marcos L

    2016-03-01

    Calcium and calmodulin (CaM) are important players in eukaryote cell signaling. In the present study, by using a knockin approach, we demonstrated the expression and localization of CaM in all erythrocytic stages of Plasmodium falciparum. Under extracellular Ca(2+)-free conditions, calmidazolium (CZ), a potent CaM inhibitor, promoted a transient cytosolic calcium ([Ca(2+)]cyt) increase in isolated trophozoites, indicating that CZ mobilizes intracellular sources of calcium. In the same extracellular Ca(2+)-free conditions, the [Ca(2+)]cyt rise elicited by CZ treatment was ~3.5 fold higher when the endoplasmic reticulum (ER) calcium store was previously depleted ruling out the mobilization of calcium from the ER by CZ. The effects of the Ca(2+)/H(+) ionophore ionomycin (ION) and the Na(+)/H(+) ionophore monensin (MON) suggest that the [Ca(2+)]cyt-increasing effect of CZ is driven by the removal of Ca(2+) from at least one Ca(2+)-CaM-related (CaMR) protein as well as by the mobilization of Ca(2+) from intracellular acidic calcium stores. Moreover, we showed that the mitochondrion participates in the sequestration of the cytosolic Ca(2+) elicited by CZ. Finally, the modulation of membrane Ca(2+) channels by CZ and thapsigargin (THG) was demonstrated. The opened channels were blocked by the unspecific calcium channel blocker Co(2+) but not by 2-APB (capacitative calcium entry inhibitor) or nifedipine (L-type Ca(2+) channel inhibitor). Taken together, the results suggested that one CaMR protein is an important modulator of calcium signaling and homeostasis during the Plasmodium intraerythrocytic cell cycle, working as a relevant intracellular Ca(2+) reservoir in the parasite. PMID:26689736

  14. Sport entries and qualification manual: Nanjing 2014

    OpenAIRE

    2014-01-01

    Sport entries constitute an important part of the delegation registration process of the Nanjing 2014 Summer Youth Olympic Games. This manual aims to introduce to NOCs the process, relevant policies and requirements regarding sport entries so as to ensure that NOCs can successfully complete the entries for their athletes to the Nanjing 2014 Youth Olympic Games.

  15. 19 CFR 122.42 - Aircraft entry.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 1 2010-04-01 2010-04-01 false Aircraft entry. 122.42 Section 122.42 Customs... AIR COMMERCE REGULATIONS Aircraft Entry and Entry Documents; Electronic Manifest Requirements for Passengers, Crew Members, and Non-Crew Members Onboard Commercial Aircraft Arriving In, Continuing...

  16. Architecture of the mitochondrial calcium uniporter.

    Science.gov (United States)

    Oxenoid, Kirill; Dong, Ying; Cao, Chan; Cui, Tanxing; Sancak, Yasemin; Markhard, Andrew L; Grabarek, Zenon; Kong, Liangliang; Liu, Zhijun; Ouyang, Bo; Cong, Yao; Mootha, Vamsi K; Chou, James J

    2016-05-12

    Mitochondria from many eukaryotic clades take up large amounts of calcium (Ca(2+)) via an inner membrane transporter called the uniporter. Transport by the uniporter is membrane potential dependent and sensitive to ruthenium red or its derivative Ru360 (ref. 1). Electrophysiological studies have shown that the uniporter is an ion channel with remarkably high conductance and selectivity. Ca(2+) entry into mitochondria is also known to activate the tricarboxylic acid cycle and seems to be crucial for matching the production of ATP in mitochondria with its cytosolic demand. Mitochondrial calcium uniporter (MCU) is the pore-forming and Ca(2+)-conducting subunit of the uniporter holocomplex, but its primary sequence does not resemble any calcium channel studied to date. Here we report the structure of the pore domain of MCU from Caenorhabditis elegans, determined using nuclear magnetic resonance (NMR) and electron microscopy (EM). MCU is a homo-oligomer in which the second transmembrane helix forms a hydrophilic pore across the membrane. The channel assembly represents a new solution of ion channel architecture, and is stabilized by a coiled-coil motif protruding into the mitochondrial matrix. The critical DXXE motif forms the pore entrance, which features two carboxylate rings; based on the ring dimensions and functional mutagenesis, these rings appear to form the selectivity filter. To our knowledge, this is one of the largest membrane protein structures characterized by NMR, and provides a structural blueprint for understanding the function of this channel. PMID:27135929

  17. 76 FR 66875 - Informal Entry Limit and Removal of a Formal Entry Requirement

    Science.gov (United States)

    2011-10-28

    ... increasing the informal entry limit to $2,500 will save the trade community approximately $11 million in... informal entry from $2,000 to $2,500. Unless exempt under a free trade agreement and in addition to any..., 143, 145, and 148 RIN 1515-AD69 Informal Entry Limit and Removal of a Formal Entry Requirement...

  18. STIM1 Controls Endothelial Barrier Function Independently of Orai1 and Ca2+ Entry

    OpenAIRE

    Shinde, Arti V.; Motiani, Rajender K.; Zhang, Xuexin; Abdullaev, Iskandar F.; Adam, Alejandro P.; González-Cobos, José C.; Zhang, Wei; Matrougui, Khalid; Vincent, Peter A.; Trebak, Mohamed

    2013-01-01

    Endothelial barrier function is critical for tissue fluid homeostasis and its disruption contributes to various pathologies, including inflammation and sepsis. Thrombin is an endogenous agonist that impairs endothelial barrier function. Here, we showed that the thrombin-induced decrease in transendothelial electric resistance of cultured human endothelial cells required the endoplasmic reticulum-localized, calcium-sensing protein STIM1, but was independent of Ca2+ entry across the plasma memb...

  19. Developing the Brand Entry Strategy

    OpenAIRE

    Gupta, Pramesh

    2004-01-01

    With more than two decades of experience in the flashlight industry, Vinpol is all set to launch the flashlights, under their brand name, into the market. This dissertation describes a process of generating a brand entry strategy for Vinpol. A model is proposed that adapts the approach of 4Ps and Relationship Marketing. The rationale for this report has come about due to initial secondary research which shows that there will be constant growth in the flashlight industry. Some factors that nee...

  20. Marketing Mix Reactions to Entry

    OpenAIRE

    Robinson, William T.

    1988-01-01

    Initial product, distribution, marketing expenditure, and price reactions by incumbents are examined for 115 entrants into oligopolistic markets. The most common reaction pattern is either no reaction or only a single reaction. It is very unusual for entrants to face reactions across the entire marketing mix. Reactions in the first two years after entry are explained as a function of the entrant's strategy, incumbent characteristics, and industry characteristics. The explanation provides insi...

  1. Bargaining agenda, timing, and entry

    OpenAIRE

    Fanti, Luciano; Buccella, Domenico

    2015-01-01

    In a unionised Cournot duopoly, the present paper extensively re-examines the subject of the bargaining scope between firms and unions. It investigates the endogenous equilibrium agenda (Right-to-Manage vs Efficient Bargaining) that can arise under three timing specification of the bargaining game both for a given duopoly and monopoly with threat of entry. A novel result is that, in sequential negotiations, Efficient Bargaining emerges in equilibrium for a range of the unions’ power larger th...

  2. SPANISH COMPANY FOREIGN MARKET ENTRY

    OpenAIRE

    Francisco J. Más; Felipe Ruiz Moreno

    2003-01-01

    The aim of this paper is to analyse the determinants of diversification mode (acquisition versus greenfield) through foreign direct investment considering various theories, such as those of mergers and acquisitions, transaction costs, the learning organisation, the institutional context of the company and the cultural environment of the host country, and to analyse the determinants of entry mode combining diversification mode with ownership structure decision (greenfield wholly-owned subsidia...

  3. Filamin and phospholipase C-ε are required for calcium signaling in the Caenorhabditis elegans spermatheca.

    Directory of Open Access Journals (Sweden)

    Ismar Kovacevic

    2013-05-01

    Full Text Available The Caenorhabditis elegans spermatheca is a myoepithelial tube that stores sperm and undergoes cycles of stretching and constriction as oocytes enter, are fertilized, and exit into the uterus. FLN-1/filamin, a stretch-sensitive structural and signaling scaffold, and PLC-1/phospholipase C-ε, an enzyme that generates the second messenger IP3, are required for embryos to exit normally after fertilization. Using GCaMP, a genetically encoded calcium indicator, we show that entry of an oocyte into the spermatheca initiates a distinctive series of IP3-dependent calcium oscillations that propagate across the tissue via gap junctions and lead to constriction of the spermatheca. PLC-1 is required for the calcium release mechanism triggered by oocyte entry, and FLN-1 is required for timely initiation of the calcium oscillations. INX-12, a gap junction subunit, coordinates propagation of the calcium transients across the spermatheca. Gain-of-function mutations in ITR-1/IP3R, an IP3-dependent calcium channel, and loss-of-function mutations in LFE-2, a negative regulator of IP3 signaling, increase calcium release and suppress the exit defect in filamin-deficient animals. We further demonstrate that a regulatory cassette consisting of MEL-11/myosin phosphatase and NMY-1/non-muscle myosin is required for coordinated contraction of the spermatheca. In summary, this study answers long-standing questions concerning calcium signaling dynamics in the C. elegans spermatheca and suggests FLN-1 is needed in response to oocyte entry to trigger calcium release and coordinated contraction of the spermathecal tissue.

  4. Evidence for a possible calcium flux dependent cardiomyopathy in hyperthyroidism

    International Nuclear Information System (INIS)

    This study was designed to test the hypothesis that the impaired functional cardiac reserve to exercise in hyperthyroidism is related to alterations in the regulation of calcium transport. In 2l hyperthyroid patients, the left ventricular ejection fraction (LVEF) was measured using equilibrium gated radionuclide angiocardiography at rest and during supine dynamic exercise. After a recovery period, the patients performed a second exercise study after random administration of Verapamil, a calcium entry blocker (11 pts), or propanolol, a beta adrenergic antagonist (10 pts) for comparison. The results showed i) normal resting LVEF with no significant change during exercise before any medication, ii) resting LVEF significantly decreased after Propanolol, and no significantly changed after Verapamil, iii) during exercise, significant increase of LVEF after Verapamil, and no significant change after Propanolol. These results are consistent with previous studies showing that abnormal change in LVEF during exercise in hyperthyroidism seems independent of beta adrenergic activation, and suggest a reversible functional cardiomyopathy dependent of calcium transporting systems

  5. Predicting the Diversity of Foreign Entry Modes

    DEFF Research Database (Denmark)

    Hashai, Niron; Geisler Asmussen, Christian; Benito, Gabriel;

    2007-01-01

    This paper expands entry mode literature by referring to multiple modes exerted in different value chain activities within and across host markets, rather than to a single entry mode at the host market level. Scale of operations and knowledge intensity are argued to affect firms' entry mode...... diversity across value chain activities and host markets. Analyzing a sample of Israeli based firms we show that larger firms exhibit a higher degree of entry mode diversity both across value chain activities and across host markets. Higher levels of knowledge intensity are also associated with more...... diversity in firms' entry modes across both dimensions....

  6. Neuronal calcium sparks and intracellular calcium “noise”

    OpenAIRE

    Melamed-Book, Naomi; Kachalsky, Sylvia G.; Kaiserman, Igor; Rahamimoff, Rami

    1999-01-01

    Intracellular calcium ions are involved in many forms of cellular function. To accommodate so many control functions, a complex spatiotemporal organization of calcium signaling has developed. In both excitable and nonexcitable cells, calcium signaling was found to fluctuate. Sudden localized increases in the intracellular calcium concentration—or calcium sparks—were found in heart, striated and smooth muscle, Xenopus Laevis oocytes, and HeLa and P12 cells. In the nervous system, intracellular...

  7. Calcium addition in straw gasification

    DEFF Research Database (Denmark)

    Risnes, H.; Fjellerup, Jan Søren; Henriksen, Ulrik Birk;

    2003-01-01

    The present work focuses on the influence of calcium addition in gasification. The inorganic¿organic element interaction as well as the detailed inorganic¿inorganic elements interaction has been studied. The effect of calcium addition as calcium sugar/molasses solutions to straw significantly...... affected the ash chemistry and the ash sintering tendency but much less the char reactivity. Thermo balance test are made and high-temperature X-ray diffraction measurements are performed, the experimental results indicate that with calcium addition major inorganic¿inorganic reactions take place very late...... calcium binds silicon primarily as calcium silicates and less as potassium calcium silicates....

  8. Atmospheric Entry Experiments at IRS

    Science.gov (United States)

    Auweter-Kurtz, M.; Endlich, P.; Herdrich, G.; Kurtz, H.; Laux, T.; Löhle, S.; Nazina, N.; Pidan, S.

    2002-01-01

    Entering the atmosphere of celestial bodies, spacecrafts encounter gases at velocities of several km/s, thereby being subjected to great heat loads. The thermal protection systems and the environment (plasma) have to be investigated by means of computational and ground facility based simulations. For more than a decade, plasma wind tunnels at IRS have been used for the investigation of TPS materials. Nevertheless, ground tests and computer simulations cannot re- place space flights completely. Particularly, entry mission phases encounter challenging problems, such as hypersonic aerothermodynamics. Concerning the TPS, radiation-cooled materials used for reuseable spacecrafts and ablator tech- nologies are of importance. Besides the mentioned technologies, there is the goal to manage guidance navigation, con- trol, landing technology and inflatable technologies such as ballutes that aim to keep vehicles in the atmosphere without landing. The requirement to save mass and energy for planned interplanetary missions such as Mars Society Balloon Mission, Mars Sample Return Mission, Mars Express or Venus Sample Return mission led to the need for manoeuvres like aerocapture, aero-breaking and hyperbolic entries. All three are characterized by very high kinetic vehicle energies to be dissipated by the manoeuvre. In this field flight data are rare. The importance of these manoeuvres and the need to increase the knowledge of required TPS designs and behavior during such mission phases point out the need of flight experiments. As result of the experience within the plasma diagnostic tool development and the plasma wind tunnel data base, flight experiments like the PYrometric RE-entry EXperiment PYREX were developed, fully qualified and successfully flown. Flight experiments such as the entry spectrometer RESPECT and PYREX on HOPE-X are in the conceptual phase. To increase knowledge in the scope of atmospheric manoeuvres and entries, data bases have to be created combining both

  9. 17beta-estradiol rapidly mobilizes intracellular calcium from ryanodine-receptor-gated stores via a PKC-PKA-Erk-dependent pathway in the human eccrine sweat gland cell line NCL-SG3.

    LENUS (Irish Health Repository)

    Muchekehu, Ruth W

    2008-09-01

    We describe a novel rapid non-genomic effect of 17beta-estradiol (E2) on intracellular Ca2+ ([Ca2+]i) signalling in the eccrine sweat gland epithelial cell line NCL-SG3. E2 had no observable effect on basal [Ca2+]i, however exposure of cells to E2 in the presence of the microsomal Ca2+ ATPase pump inhibitor, thapsigargin, produced a secondary, sustained increase in [Ca2+]i compared to thapsigargin treatment alone, where cells responded with a transient single spike-like increase in [Ca2+]i. The E2-induced increase in [Ca2+]i was not dependent on the presence of extracellular calcium and was completely abolished by ryanodine (100 microM). The estrogen receptor antagonist ICI 182,780 (1 microM) prevented the E2-induced effects suggesting a role for the estrogen receptor in the release of [Ca2+]i from ryanodine-receptor-gated stores. The E2-induced effect on [Ca2+]i could also be prevented by the protein kinase C delta (PKCdelta)-specific inhibitor rottlerin (10 microM), the protein kinase A (PKA) inhibitor Rp-adenosine 3\\

  10. Calcium binding by dietary fibre

    International Nuclear Information System (INIS)

    Dietary fibre from plants low in phytate bound calcium in proportion to its uronic-acid content. This binding by the non-cellulosic fraction of fibre reduces the availability of calcium for small-intestinal absorption, but the colonic microbial digestion of uronic acids liberates the calcium. Thus the ability to maintain calcium balance on high-fibre diets may depend on the adaptive capacity on the colon for calcium. (author)

  11. [Calcium suppletion for patients who use gastric acid inhibitors: calcium citrate or calcium carbonate?].

    NARCIS (Netherlands)

    Jonge, H.J. de; Gans, R.O.; Huls, G.A.

    2012-01-01

    Various calcium supplements are available for patients who have an indication for calcium suppletion. American guidelines and UpToDate recommend prescribing calcium citrate to patients who use antacids The rationale for this advice is that water-insoluble calcium carbonate needs acid for adequate ab

  12. M3R介导的cAMP-PKA信号途径对L-型钙通道的调控作用研究%Effects of M3 Receptor on L-type Calcium Channels by cAMP-PKA Signal Pathway

    Institute of Scientific and Technical Information of China (English)

    栾海蓉; 董琦; 王得利; 李海林; 吴红

    2012-01-01

    Objective To investigate the effects of M3 receptor agonist choline on L-type calcium channels by cAMP-PKA signal pathway. Methods Whole cell patch clamp technique was used to record L-type calcium current. Laser scanning confocal microscope( LSCM )was employed to measure the concentration of intracellular free calcium. Results The application of choline reduced the density of peak Ica-L from( 9.07 ±0. 68)pA/pf to(5.58 ±0.62 )pA/pP( n =4,vs control,P <0.01 ),H89 with choline reduced the density of peak Ica-L to( 7.68 ±0.75 )pA/pF,whose amplitude was higher than that of choline group( n =4,vs choline, P< 0.01 ). LSCM recorded that KC1 induced determined by used[ Ca2 + ]I increasing could be depressed by choline, and also depressed by H89 with choline, whose amplitude is higher than that of choline group( n=30,vs choline,P<0.05 ). Conclusion Choline reduces[ Ca2 + ]I via inhibition of cAMP-PKA signal pathway of L-type calcium channel, which is possibly involved in the mechanism of its protective effects on myocardial injury.%目的 研究M3受体激动剂通过cAMP-PKA信号途径对L-型钙通道的影响.方法 应用全细胞膜片钳技术记录M3受体激动剂胆碱对大鼠单个心室肌细胞L-型钙通道电流(ICa-L)的影响;采用激光扫描共聚焦技术观察细胞内钙离子的变化.结果 胆碱使大鼠心室肌细胞ICa-L密度从(9.07±0.68)pA/pF减少至(5.58 ±0.62)pA/pF(n=4,与对照组相比,P<0.01),H89加胆碱组使ICa-L电流密度减少至(7.68±0.75),幅度明显高于胆碱组(n=4,与胆碱组相比,P<0.01).胆碱抑制KCl除极诱导的心肌细胞[Ca2+]i的升高,从(2.83±0.08)降至(1.17±0.09)FI/FI0(n=30,与KCl组相比,P<0.01),胆碱与H89组可使[Ca2+]i降至(1.65±0.17)FI/FI0,幅度高于胆碱组(n=30,与胆碱组相比,P<0.05).结论 M3受体激动剂胆碱通过抑制PKA活性调控L-型钙通道,使外钙内流减少,降低细胞[Ca2+]i,从而发挥抗心肌保护作用.

  13. Calcium regulates caveolin-1 expression at the transcriptional level

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Xiao-Yan; Huang, Cheng-Cheng; Kan, Qi-Ming [Laboratory of Tumor Biology and Glycobiology, Department of Life Sciences, Shenyang Pharmaceutical University, Shenyang 110016, People' s Republic of China (China); Li, Yan [Experimental Animal Center, Department of Life Sciences, Shenyang Pharmaceutical University, Shenyang 110016, People' s Republic of China (China); Liu, Dan; Zhang, Xue-Cheng [Laboratory of Tumor Biology and Glycobiology, Department of Life Sciences, Shenyang Pharmaceutical University, Shenyang 110016, People' s Republic of China (China); Sato, Toshinori [Department of Biosciences and Informatics, Keio University, Hiyoshi, Yokohama 223-8522 (Japan); Yamagata, Sadako [Laboratory of Tumor Biology and Glycobiology, Department of Life Sciences, Shenyang Pharmaceutical University, Shenyang 110016, People' s Republic of China (China); Yamagata, Tatsuya, E-mail: tcyamagata@gmail.com [Laboratory of Tumor Biology and Glycobiology, Department of Life Sciences, Shenyang Pharmaceutical University, Shenyang 110016, People' s Republic of China (China)

    2012-09-28

    Highlights: Black-Right-Pointing-Pointer Caveolin-1 expression is regulated by calcium signaling at the transcriptional level. Black-Right-Pointing-Pointer An inhibitor of or siRNA to L-type calcium channel suppressed caveolin-1 expression. Black-Right-Pointing-Pointer Cyclosporine A or an NFAT inhibitor markedly reduced caveolin-1 expression. Black-Right-Pointing-Pointer Caveolin-1 regulation by calcium signaling is observed in several mouse cell lines. -- Abstract: Caveolin-1, an indispensable component of caveolae serving as a transformation suppressor protein, is highly expressed in poorly metastatic mouse osteosarcoma FBJ-S1 cells while highly metastatic FBJ-LL cells express low levels of caveolin-1. Calcium concentration is higher in FBJ-S1 cells than in FBJ-LL cells; therefore, we investigated the possibility that calcium signaling positively regulates caveolin-1 in mouse FBJ-S1 cells. When cells were treated with the calcium channel blocker nifedipine, cyclosporin A (a calcineurin inhibitor), or INCA-6 (a nuclear factor of activated T-cells [NFAT] inhibitor), caveolin-1 expression at the mRNA and protein levels decreased. RNA silencing of voltage-dependent L-type calcium channel subunit alpha-1C resulted in suppression of caveolin-1 expression. This novel caveolin-1 regulation pathway was also identified in mouse NIH 3T3 cells and Lewis lung carcinoma cells. These results indicate that caveolin-1 is positively regulated at the transcriptional level through a novel calcium signaling pathway mediated by L-type calcium channel/Ca{sup 2+}/calcineurin/NFAT.

  14. Replication of Alphaviruses: A Review on the Entry Process of Alphaviruses into Cells

    Directory of Open Access Journals (Sweden)

    Jason Yat-Sing Leung

    2011-01-01

    Full Text Available Alphaviruses are small, enveloped viruses, ~70 nm in diameter, containing a single-stranded, positive-sense, RNA genome. Viruses belonging to this genus are predominantly arthropod-borne viruses, known to cause disease in humans. Their potential threat to human health was most recently exemplified by the 2005 Chikungunya virus outbreak in La Reunion, highlighting the necessity to understand events in the life-cycle of these medically important human pathogens. The replication and propagation of viruses is dependent on entry into permissive cells. Viral entry is initiated by attachment of virions to cells, leading to internalization, and uncoating to release genetic material for replication and propagation. Studies on alphaviruses have revealed entry via a receptor-mediated, endocytic pathway. In this paper, the different stages of alphavirus entry are examined, with examples from Semliki Forest virus, Sindbis virus, Chikungunya virus, and Venezuelan equine encephalitis virus described.

  15. Interaction of KSHV with Host Cell Surface Receptors and Cell Entry

    Directory of Open Access Journals (Sweden)

    Mohanan Valiya Veettil

    2014-10-01

    Full Text Available Virus entry is a complex process characterized by a sequence of events. Since the discovery of KSHV in 1994, tremendous progress has been made in our understanding of KSHV entry into its in vitro target cells. KSHV entry is a complex multistep process involving viral envelope glycoproteins and several cell surface molecules that is utilized by KSHV for its attachment and entry. KSHV has a broad cell tropism and the attachment and receptor engagement on target cells have an important role in determining the cell type-specific mode of entry. KSHV utilizes heparan sulfate, integrins and EphrinA2 molecules as receptors which results in the activation of host cell pre-existing signal pathways that facilitate the subsequent cascade of events resulting in the rapid entry of virus particles, trafficking towards the nucleus followed by viral and host gene expression. KSHV enters human fibroblast cells by dynamin dependant clathrin mediated endocytosis and by dynamin independent macropinocytosis in dermal endothelial cells. Once internalized into endosomes, fusion of the viral envelope with the endosomal membranes in an acidification dependent manner results in the release of capsids which subsequently reaches the nuclear pore vicinity leading to the delivery of viral DNA into the nucleus. In this review, we discuss the principal mechanisms that enable KSHV to interact with the host cell surface receptors as well as the mechanisms that are required to modulate cell signaling machinery for a successful entry.

  16. Dissociation of Ca sup 2+ entry and Ca sup 2+ mobilization responses to angiotensin II in bovine adrenal chromaffin cells

    Energy Technology Data Exchange (ETDEWEB)

    Stauderman, K.A.; Pruss, R.M. (Merrell Dow Research Institute, Cincinnati, OH (USA))

    1989-11-05

    In fura-2-loaded bovine adrenal chromaffin cells, 0.5 microM angiotensin II (AII) stimulated a 185 +/- 19 nM increase of intracellular-free calcium (( Ca2+)i) approximately 3 s after addition. The time from the onset of the response until achieving 50% recovery (t 1/2) was 67 +/- 10 s. Concomitantly, AII stimulated both the release of 45Ca2+ from prelabeled cells, and a 4-5-fold increase of (3H)inositol 1,4,5-trisphosphate (( 3H)Ins(1,4,5)P3) levels. In the presence of 50 microM LaCl3, or when extracellular-free Ca2+ (( Ca2+)o) was less than 100 nM, AII still rapidly increased (Ca2+)i by 95-135 nM, but the t 1/2 for recovery was then only 23-27 s. In medium with 1 mM MnCl2 present, AII also stimulated a small amount of Mn2+ influx, as judged by quenching of the fura-2 signal. When (Ca2+)o was normal (1.1 mM) or low (less than 60 nM), 1-2 microM ionomycin caused (Ca2+)i to increase 204 +/- 26 nM, while also releasing 45-55% of bound 45Ca2+. With low (Ca2+)o, ionomycin pretreatment abolished both the (Ca2+)i increase and 45Ca2+ release stimulated by AII. However, after ionomycin pretreatment in normal medium, AII produced a La3+-inhibitable increase of (Ca2+)i (103 +/- 13 nM) with a t 1/2 of 89 +/- 8 s, but no 45Ca2+ release. No pretreatment condition altered AII-induced formation of (3H)Ins(1,4,5)P3. We conclude that AII increased (Ca2+)i via rapid and transient Ca2+ mobilization from Ins(1,4,5)P3- and ionomycin-sensitive stores, accompanied (and/or followed) by Ca2+ entry through a La3+-inhibitable divalent cation pathway. Furthermore, the ability of AII to activate Ca2+ entry in the absence of Ca2+ mobilization (i.e. after ionomycin pretreatment) suggests a receptor-linked stimulus other than Ca2+ mobilization initiates Ca2+ entry.

  17. Functional separation of deep cytoplasmic calcium from subplasmalemmal space calcium in cultured human uterine smooth muscle cells.

    Science.gov (United States)

    Young, Roger C; Zhang, PeiSheng

    2004-07-01

    For smooth muscle, two important functions of free intracellular calcium (Ca(2+)(i)) are modulation of plasma membrane excitability properties and modulation of the contractile apparatus. As proposed by van Breemen, Ca(2+)(i) can be divided into the subplasmalemmal space (Ca(2+)(sps)) and the deep cytosol (Ca(2+)(d)) by the superficial calcium buffer barrier. Using these distinctions, Ca(2+)(sps) activates the large conductance calcium-activated potassium channel (BK), and Ca(2+)(d) binds calcium-dependent fluorescent probes in the cytoplasm. We present here combined fluorescence-patch clamp experiments designed to simultaneously assess Ca(2+)(d) and Ca(2+)(sps) in cultured human uterine smooth muscle cells. Open probabilities (P(o)) of the BK channel were measured using the cell-attached patch clamp technique. P(o) was used to approximate changes of [Ca(2+)(sps)]. Relative concentrations of Ca(2+)(d) were approximated by observing fluorescence of Calcium green-1 (F). Under control conditions, we found similar time courses for rises of P(o) and F following 10nM oxytocin (OT) addition. In parallel experiments, but with lanthanum (La(3+)) added to the bath to block transmembrane calcium flux, P(o) was only slightly affected, but F increases were delayed and blunted. These data paradoxically indicate that following OT stimulation, the primary source of calcium for Ca(2+)(sps) is internal stores, and calcium entry from the extracellular space is required to raise Ca(2+)(d). When cells were exposed to cyclopiazonic acid (CPA) to release SR calcium stores, P(o) increased slowly, then persisted at large values. The persistence of P(o) rises suggests that removal of calcium from the subplasmalemmal space is primarily via reuptake into the SR. In the presence of La(3+), OT-induced rises of F were slightly prolonged, suggesting that transmembrane calcium flux contributes to decreasing Ca(2+)(d), but is not the primary mechanism. In summary, these data demonstrate that Ca(2

  18. Multiscale Vision Model Highlights Spontaneous Glial Calcium Waves Recorded by 2-Photon Imaging in Brain Tissue

    DEFF Research Database (Denmark)

    Brazhe, Alexey; Mathiesen, Claus; Lauritzen, Martin

    2013-01-01

    Intercellular glial calcium waves constitute a signaling pathway which can be visualized by fluorescence imaging of cytosolic Ca2+ changes. However, there is a lack of procedures for sensitive and reliable detection of calcium waves in noisy multiphoton imaging data. Here we extend multiscale vis...

  19. PACAP signaling to DREAM: a cAMP-dependent pathway that regulates cortical astrogliogenesis.

    Science.gov (United States)

    Vallejo, Mario

    2009-04-01

    Astrocytes constitute a very abundant cell type in the mammalian central nervous system and play critical roles in brain function. During development, astrocytes are generated from neural progenitor cells only after these cells have generated neurons. This so called gliogenic switch is tightly regulated by intrinsic factors that inhibit the generation of astrocytes during the neurogenic period. Once neural progenitors acquire gliogenic competence, they differentiate into astrocytes in response to specific extracellular signals. Some of these signals are delivered by neurotrophic cytokines via activation of the gp130-JAK-signal transducer and activator of transcription system, whereas others depend on the activity of pituitary adenylate cyclase-activating polypeptide (PACAP) on specific PAC1 receptors that stimulate the production of cAMP. This results in the activation of the small GTPases Rap1 and Ras, and in the cAMP-dependent entry of extracellular calcium into the cell. Calcium, in turn, stimulates the transcription factor downstream regulatory element antagonist modulator (DREAM), which is bound to specific sites of the promoter of the glial fibrillary acidic protein gene, stimulating its expression during astrocyte differentiation. Lack of DREAM in vivo results in alterations in the number of neurons and astrocytes generated during development. Thus, the PACAP-cAMP-Ca(2+)-DREAM signaling cascade constitutes an important pathway to activate glial-specific gene expression during astrocyte differentiation. PMID:19238593

  20. Lipid body accumulation alters calcium signaling dynamics in immune cells

    Science.gov (United States)

    Greineisen, William E.; Speck, Mark; Shimoda, Lori M.N.; Sung, Carl; Phan, Nolwenn; Maaetoft-Udsen, Kristina; Stokes, Alexander J.; Turner, Helen

    2014-01-01

    Summary There is well-established variability in the numbers of lipid bodies (LB) in macrophages, eosinophils, and neutrophils. Similarly to the steatosis observed in adipocytes and hepatocytes during hyperinsulinemia and nutrient overload, immune cell LB hyper-accumulate in response to bacterial and parasitic infection and inflammatory presentations. Recently we described that hyperinsulinemia, both in vitro and in vivo, drives steatosis and phenotypic changes in primary and transformed mast cells and basophils. LB reach high numbers in these steatotic cytosols, and here we propose that they could dramatically impact the transcytoplasmic signaling pathways. We compared calcium release and influx responses at the population and single cell level in normal and steatotic model mast cells. At the population level, all aspects of FcεRI-dependent calcium mobilization, as well as activation of calcium-dependent downstream signalling targets such as NFATC1 phosphorylation are suppressed. At the single cell level, we demonstrate that LB are both sources and sinks of calcium following FcεRI cross-linking. Unbiased analysis of the impact of the presence of LB on the rate of trans-cytoplasmic calcium signals suggest that LB enrichment accelerates calcium propagation, which may reflect a Bernoulli effect. LB abundance thus impacts this fundamental signalling pathway and its downstream targets. PMID:25016314

  1. Inhibition of parathyroid hormone release by maitotoxin, a calcium channel activator

    International Nuclear Information System (INIS)

    Maitotoxin, a toxin derived from a marine dinoflagellate, is a potent activator of voltage-sensitive calcium channels. To further test the hypothesis that inhibition of PTH secretion by calcium is mediated via a calcium channel we studied the effect of maitotoxin on dispersed bovine parathyroid cells. Maitotoxin inhibited PTH release in a dose-dependent fashion, and inhibition was maximal at 1 ng/ml. Chelation of extracellular calcium by EGTA blocked the inhibition of PTH by maitotoxin. Maitotoxin enhanced the effects of the dihydropyridine calcium channel agonist (+)202-791 and increased the rate of radiocalcium uptake in parathyroid cells. Pertussis toxin, which ADP-ribosylates and inactivates a guanine nucleotide regulatory protein that interacts with calcium channels in the parathyroid cell, did not affect the inhibition of PTH secretion by maitotoxin. Maitotoxin, by its action on calcium channels allows entry of extracellular calcium and inhibits PTH release. Our results suggest that calcium channels are involved in the release of PTH. Inhibition of PTH release by maitotoxin is not sensitive to pertussis toxin, suggesting that maitotoxin may act distal to the site interacting with a guanine nucleotide regulatory protein, or maitotoxin could interact with other ions or second messengers to inhibit PTH release

  2. Formation and actions of calcium-mobilizing messenger, inositol 1,4,5-trisphosphate

    International Nuclear Information System (INIS)

    A variety of surface membrane receptors can activate a phospholipase C, which degrades phosphatidylinositol 4,5-bisphosphate liberating a calcium mobilizing second messenger, inositol 1,4,5-trisphosphate [(1,4,5)IP3]. The coupling of surface receptors to the phospholipase C involves one or more quanine nucleotide-dependent regulatory proteins that are similar but not identical to those that regulate adenylate cyclase. (1,4,5)IP3 has been shown to release Ca2+ from a portion of the endoplasmic reticulum and is believed responsible for the initial phase of Ca2+ mobilization ascribed to internal Ca2+ release. (1,4,5)IP3 acts by binding to a specific receptor that either is a component of, or regulates, a Ca2+ ion channel. The release of Ca2+ from the (1,4,5)IP3-sensitive component of the endoplasmic reticulum may secondarily activate the second phase of Ca2+ mobilization, which involves Ca2+ entry. (1,4,5)IP3 is metabolized by two pathways. One involves the action of a 5-phosphatase that degrades (1,4,5)IP3 to inositol 1,4-bisphosphate, whereas the other involves a 3-kinase that phosphorylates (1,4,5)IP3 to produce inositol 1,3,4,5-tetrakisphosphate. The significance of this dual metabolism is not known, but it may be important in rapidly extinguishing the Ca2+-releasing activity (1,4,5)IP3

  3. Who Benefits from Store Brand Entry?

    OpenAIRE

    Koen Pauwels; Shuba Srinivasan

    2004-01-01

    Store brand entry has become a key issue in marketing as it may structurally change the performance of and the interactions among all market players. Based on their multivariate time-series analysis, the authors demonstrate permanent performance effects of store brand entry, typically benefiting the retailer, the consumers, and premium-brand manufacturers, while harming second-tier brand manufacturers. For the , they consistently find two of store brand entry: . This increase in unit margins ...

  4. Entry Strategies, Welfare Analysis and Firms’ Behaviors

    OpenAIRE

    Wang Xun; Luo Ting

    2007-01-01

    Before serving a new market, a multinational enterprise (MNE) has several entry strategies, which include foreign direct investment (FDI), joint venture (JV) and exclusive licensing (EL). Entry cost, market size of the host country, and the discount rate are the main determinants when the MNE chooses its optimal entry strategy. At a certain level of ownership share that the MNE holds, JV will generate the highest social welfare. If firms can choose between competition and collusion, at differ...

  5. Arachidonic acid and calcium metabolism in rnelittin stimulated neutrophils

    Directory of Open Access Journals (Sweden)

    Ole H. Nielsen

    1992-01-01

    Full Text Available Melittin, the predominant fraction of bee venom proteins, was studied in an experimental model of human neutrophil granulocytes to reveal its influence on eicosanoid release, metabolism and receptor function in relation to intracellular calcium metabolism. Melittin (2 μmol/l was as potent as the calcium ionophore A23187 (10 μmol/l for activation of 5-lipoxygenase, releasing arachidonate only from phosphatidyl-choline and phosphatidyl-ethanolamine of cellular membranes, as judged from the decreases in radioactivity by 15.4% and 30.5%, respectively. The mechanism responsible for the release of arachidonate from cellular membranes is closely coupled to cellular calcium metabolism, and melittin was found to promote calcium entry through receptor gated calcium channels, probably due to an activation of phospholipase A2. Furthermore, a down-regulation of leukotriene B4 receptors was seen. The maximal number of binding sites per cell was reduced from a median of 1520 to 950 with melittin (1 μmol/l. The study has revealed some factors important for the inflammatory mechanisms mediated by melittin.

  6. Osteoclast cytosolic calcium, regulated by voltage-gated calcium channels and extracellular calcium, controls podosome assembly and bone resorption

    Science.gov (United States)

    Miyauchi, A.; Hruska, K. A.; Greenfield, E. M.; Duncan, R.; Alvarez, J.; Barattolo, R.; Colucci, S.; Zambonin-Zallone, A.; Teitelbaum, S. L.; Teti, A.

    1990-01-01

    The mechanisms of Ca2+ entry and their effects on cell function were investigated in cultured chicken osteoclasts and putative osteoclasts produced by fusion of mononuclear cell precursors. Voltage-gated Ca2+ channels (VGCC) were detected by the effects of membrane depolarization with K+, BAY K 8644, and dihydropyridine antagonists. K+ produced dose-dependent increases of cytosolic calcium ([Ca2+]i) in osteoclasts on glass coverslips. Half-maximal effects were achieved at 70 mM K+. The effects of K+ were completely inhibited by dihydropyridine derivative Ca2+ channel blocking agents. BAY K 8644 (5 X 10(-6) M), a VGCC agonist, stimulated Ca2+ entry which was inhibited by nicardipine. VGCCs were inactivated by the attachment of osteoclasts to bone, indicating a rapid phenotypic change in Ca2+ entry mechanisms associated with adhesion of osteoclasts to their resorption substrate. Increasing extracellular Ca2+ ([Ca2+]e) induced Ca2+ release from intracellular stores and Ca2+ influx. The Ca2+ release was blocked by dantrolene (10(-5) M), and the influx by La3+. The effects of [Ca2+]e on [Ca2+]i suggests the presence of a Ca2+ receptor on the osteoclast cell membrane that could be coupled to mechanisms regulating cell function. Expression of the [Ca2+]e effect on [Ca2+]i was similar in the presence or absence of bone matrix substrate. Each of the mechanisms producing increases in [Ca2+]i, (membrane depolarization, BAY K 8644, and [Ca2+]e) reduced expression of the osteoclast-specific adhesion structure, the podosome. The decrease in podosome expression was mirrored by a 50% decrease in bone resorptive activity. Thus, stimulated increases of osteoclast [Ca2+]i lead to cytoskeletal changes affecting cell adhesion and decreasing bone resorptive activity.

  7. Gravimetric Determination of Calcium as Calcium Carbonate Hydrate.

    Science.gov (United States)

    Henrickson, Charles H.; Robinson, Paul R.

    1979-01-01

    The gravimetric determination of calcium as calcium carbonate is described. This experiment is suitable for undergraduate quantitative analysis laboratories. It is less expensive than determination of chloride as silver chloride. (BB)

  8. Binding of [125I]iodipine to parathyroid cell membranes: Evidence of a dihydropyridine-sensitive calcium channel

    International Nuclear Information System (INIS)

    The parathyroid cell is unusual, in that an increase in extracellular calcium concentrations inhibits PTH release. Calcium channels are glycoproteins that span cell membranes and allow entry of extracellular calcium into cells. We have demonstrated that the calcium channel agonist (+)202-791, which opens calcium channels, inhibits PTH release and that the antagonist (-)202-791, which closes calcium channels, stimulates PTH release. To identify the calcium channels responsible for these effects, we used a radioligand that specifically binds to calcium channels. Bovine parathyroid cell membranes were prepared and incubated under reduced lighting with [125I] iodipine (SA, 2000 Ci/mmol), which recognizes 1,4-dihydropyridine-sensitive calcium channels. Bound ligand was separated from free ligand by rapid filtration through Whatman GF/B filters. Nonspecific binding was measured by the inclusion of nifedipine at 10 microM. Specific binding represented approximately 40% of the total binding. The optimal temperature for [125I] iodipine binding was 4 C, and binding reached equilibrium by 30 min. The equilibrium dissociation constant (Kd) was approximately 550 pM, and the maximum number of binding sites was 780 fmol/mg protein. Both the calcium channel agonist (+)202-791 and antagonist (-)202-791 competitively inhibited [125I] iodipine binding, with 50% inhibition concentrations of 20 and 300 nM, respectively. These data indicate the presence of dihydropyridine-sensitive calcium channels on parathyroid cell membranes

  9. Dissection of the insulin signaling pathway via quantitative phosphoproteomics

    DEFF Research Database (Denmark)

    Krüger, Marcus; Kratchmarova, Irina; Blagoev, Blagoy;

    2008-01-01

    spectrum of the tyrosine phosphorylation cascade, we have defined the tyrosine-phosphoproteome of the insulin signaling pathway, using high resolution mass spectrometry in combination with phosphotyrosine immunoprecipitation and stable isotope labeling by amino acids in cell culture (SILAC) in...... calcium transporting ATPase SERCA2, supporting a connection to calcium signaling. The combination of quantitative phosphoproteomics with cell culture models provides a powerful strategy to dissect the insulin signaling pathways in intact cells....

  10. CALCIUM SOAP LUBRICANTS

    OpenAIRE

    Alaz, Izer; Tugce, Nefise; Devrim, Balköse

    2014-01-01

    The article studies the properties of calcium stearate (CaSt2) and lubricants produced on its basis. These lubricants were prepared using sodium stearate and calcium chloride by subsidence from aqueous solutions. The CaSt2 and the light fraction of crude oil were mixed together to obtain lubricating substances. The article shows that CaSt2 had the melting temperature of 142.8 C that is higher than the melting temperature of crude oil (128 C). The compositions of obtained lubricants were stu...

  11. A Calcium-Dependent Protein Kinase Interactswith and Activates A Calcium Channel toRequlate Pollen Tube Growth

    Institute of Scientific and Technical Information of China (English)

    2014-01-01

    ABSTRACT Calcium, as a ubiquitous second messenger, plays essential roles in tip-growing cells, such as animal neu-rons, plant pollen tubes, and root hairs. However, little is known concerning the regulatory mechanisms that code anddecode Ca2+ signals in plants. The evidence presented here indicates that a calcium-dependent protein kinase, CPK32,controls polar growth of pollen tubes. Overexpression of CPK32 disrupted the polar growth along with excessive Ca2+accumulation in the tip. A search of downstream effector molecules for CPK32 led to identification of a cyclic nucleotide-gated channel, CNGC18, as an interacting partner for CPK32. Co-expression of CPK32 and CNGC18 resulted in activationof CNGC18 in Xenopus oocytes where expression of CNGC18 alone did not exhibit significant calcium channel activity.Overexpression of CNGC18 produced a growth arrest phenotype coupled with accumulation of calcium in the tip, simi-lar to that induced by CPK32 overexpression. Co-expression of CPK32 and CNGC18 had a synergistic effect leading tomore severe depolarization of pollen tube growth. These results provide a potential feed-forward mechanism in whichcalcium-activated CPK32 activates CNGC18, further promoting calcium entry during the elevation phase of Ca2+ oscilla-tions in the polar growth of pollen tubes.

  12. Caspase-dependent inhibition of store-operated Ca{sup 2+} entry into apoptosis-committed Jurkat cells

    Energy Technology Data Exchange (ETDEWEB)

    Onopiuk, Marta; Wierzbicka, Katarzyna; Brutkowski, Wojciech; Szczepanowska, Joanna [Department of Biochemistry, The Nencki Institute of Experimental Biology, Warsaw (Poland); Zablocki, Krzysztof, E-mail: k.zablocki@nencki.gov.pl [Department of Biochemistry, The Nencki Institute of Experimental Biology, Warsaw (Poland)

    2010-08-20

    Activation of T-cells triggers store-operated Ca{sup 2+} entry, which begins a signaling cascade leading to induction of appropriate gene expression and eventually lymphocyte proliferation and differentiation. The simultaneous enhancement of Fas ligand gene expression in activated cells allows the immune response to be limited by committing the activated cells to apoptosis. In apoptotic cells the store-operated calcium entry is significantly inhibited. It has been documented that moderate activation of Fas receptor may cause reversible inhibition of store-operated channels by ceramide released from hydrolyzed sphingomyelin. Here we show that activation of Fas receptor in T-cells results in caspase-dependent decrease of cellular STIM1 and Orai1 protein content. This effect may be responsible for the substantial inhibition of Ca{sup 2+} entry into Jurkat cells undergoing apoptosis. In turn, this inhibition might prevent overloading of cells with calcium and protect them against necrosis. -- Research highlights: {yields} Fas activation reduces STIM1 and Orai1 protein content in caspase dependent manner. {yields} Fas activation partially reduces mitochondrial potential in caspase dependent manner. {yields} Fas stimulation inhibits of store-operated Ca{sup 2+} entry in caspase dependent manner. {yields} Inhibition of Ca{sup 2+} entry in apoptotic cells may protect them from secondary necrosis.

  13. Foreign market entry strategies and post-entry growth: Acquisitions vs greenfield investments

    OpenAIRE

    Danchi Tan

    2009-01-01

    We examine the relationship between the foreign market entry strategy and the subsequent growth of a subsidiary. We build upon the Penrose theory of firm growth, and on the organizational economics, international management, and foreign market entry strategy literatures. We hypothesize that the post-entry growth of acquisitions is positively associated with weak and codifiable interdependence within the multinational enterprise network, whereas the post-entry growth of greenfield investments ...

  14. Macropinocytosis is the Entry Mechanism of Amphotropic Murine Leukemia Virus

    DEFF Research Database (Denmark)

    Rasmussen, Izabela; Vilhardt, Frederik

    2015-01-01

    infection. Understanding how pathogens and toxins exploit or divert endocytosis pathways has advanced our understanding of membrane trafficking pathways, which benefits development of new therapeutical schemes and methods of drug delivery. We show here that Murine Leukemia Virus (A-MLV) pseudotyped with the......, or NIH-3T3 cells knocked-down for caveolin expression, was unaffected. Conversely, A-MLV infection of NIH-3T3 and HeLa cells was sensitive to amiloride analogues and actin-depolymerizing drugs that interfere with macropinocytosis. Further manipulation of the actin cytoskeleton through conditional...... amphotropic (expands the host range to many mammalian cells) envelope protein gains entry into host cells by macropinocytosis. Macropinosomes form as large, fluid-filled vacuoles (up to 10 μm) following collapse of cell surface protrusions and membrane scission. We use drugs or introduction of mutant proteins...

  15. Productive infection of human immunodeficiency virus type 1 in dendritic cells requires fusion-mediated viral entry

    International Nuclear Information System (INIS)

    Human immunodeficiency virus type 1 (HIV-1) enters dendritic cells (DCs) through endocytosis and viral receptor-mediated fusion. Although endocytosis-mediated HIV-1 entry can generate productive infection in certain cell types, including human monocyte-derived macrophages, productive HIV-1 infection in DCs appears to be dependent on fusion-mediated viral entry. It remains to be defined whether endocytosed HIV-1 in DCs can initiate productive infection. Using HIV-1 infection and cellular fractionation assays to measure productive viral infection and entry, here we show that HIV-1 enters monocyte-derived DCs predominately through endocytosis; however, endocytosed HIV-1 cannot initiate productive HIV-1 infection in DCs. In contrast, productive HIV-1 infection in DCs requires fusion-mediated viral entry. Together, these results provide functional evidence in understanding HIV-1 cis-infection of DCs, suggesting that different pathways of HIV-1 entry into DCs determine the outcome of viral infection

  16. CALCIUM-INDUCED SUPRAMOLECULAR STRUCTURES IN THE CALCIUM CASEINATE SYSTEM

    Science.gov (United States)

    The molecular details deciphering the spontaneous calcium-induced protein aggregation process in the calcium caseinate system remain obscure. Understanding this complex process could lead to potential new applications of this important food ingredient. In this work, we studied calcium-induced supra...

  17. A sensor for calcium uptake

    OpenAIRE

    Collins, Sean; Meyer, Tobias

    2010-01-01

    Mitochondria — the cell’s power plants — increase their energy production in response to calcium signals in the cytoplasm. A regulator of the elusive mitochondrial calcium channel has now been identified.

  18. Children's Bone Health and Calcium

    Science.gov (United States)

    ... Trials Resources and Publications Children's Bone Health and Calcium: Condition Information Skip sharing on social media links ... straight, walk, run, and lead an active life. Calcium is one of the key dietary building blocks ...

  19. Specification of the Model 3 Entry Lexicon.

    Science.gov (United States)

    Rhode, Mary

    The Model 3 communication skills lexicon consists of three lists of words developed by the Southwest Regional Laboratory (SWRL) for use in communication skills instruction in K-6. This report documents the procedures followed in compiling the entry lexicon, the first component of the Model 3 communication skills lexicon. The entry lexicon is…

  20. Entry Mode and Performance of Nordic Firms

    DEFF Research Database (Denmark)

    Wulff, Jesper

    2015-01-01

    market entries made by Norwegian, Danish and Swedish firms suggests that the association between equity mode choice and non-location bound international experience diminishes in the presence of higher levels of multinational experience. Furthermore, firms whose entry mode choice is predicted by the model...

  1. Solar Imagery - Chromosphere - Calcium

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This dataset consists of full-disk images of the sun in Calcium (Ca) II K wavelength (393.4 nm). Ca II K imagery reveal magnetic structures of the sun from about...

  2. Expression of TRPC3 in Chinese hamster ovary cells results in calcium-activated cation currents not related to store depletion.

    Science.gov (United States)

    Zitt, C; Obukhov, A G; Strübing, C; Zobel, A; Kalkbrenner, F; Lückhoff, A; Schultz, G

    1997-09-22

    TRPC3 (or Htrp3) is a human member of the trp family of Ca2+-permeable cation channels. Since expression of TRPC3 cDNA results in markedly enhanced Ca2+ influx in response to stimulation of membrane receptors linked to phospholipase C (Zhu, X., J. Meisheng, M. Peyton, G. Bouley, R. Hurst, E. Stefani, and L. Birnbaumer. 1996. Cell. 85:661-671), we tested whether TRPC3 might represent a Ca2+ entry pathway activated as a consequence of depletion of intracellular calcium stores. CHO cells expressing TRPC3 after intranuclear injection of cDNA coding for TRPC3 were identified by fluorescence from green fluorescent protein. Expression of TRPC3 produced cation currents with little selectivity for Ca2+ over Na+. These currents were constitutively active, not enhanced by depletion of calcium stores with inositol-1,4,5-trisphosphate or thapsigargin, and attenuated by strong intracellular Ca2+ buffering. Ionomycin led to profound increases of currents, but this effect was strictly dependent on the presence of extracellular Ca2+. Likewise, infusion of Ca2+ into cell through the patch pipette increased TRPC3 currents. Therefore, TRPC3 is stimulated by a Ca2+-dependent mechanism. Studies on TRPC3 in inside-out patches showed cation-selective channels with 60-pS conductance and short (ionomycin to cells increased channel activity in cell-attached patches. Increasing the Ca2+ concentration on the cytosolic side of inside-out patches (from 0 to 1 and 30 microM), however, failed to stimulate channel activity, even in the presence of calmodulin (0.2 microM). We conclude that TRPC3 codes for a Ca2+-permeable channel that supports Ca2+-induced Ca2+-entry but should not be considered store operated. PMID:9298988

  3. 19 CFR 141.91 - Entry without required invoice.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 2 2010-04-01 2010-04-01 false Entry without required invoice. 141.91 Section 141... THE TREASURY (CONTINUED) ENTRY OF MERCHANDISE Invoices § 141.91 Entry without required invoice. If a required invoice is not available in proper form at the time the entry or entry summary documentation...

  4. Recent advances in host–virus interactomics during entry and infection

    Directory of Open Access Journals (Sweden)

    Bhattacharjee S

    2015-12-01

    Full Text Available Soumen BhattacharjeeCell and Molecular Biology Laboratory, Department of Zoology, University of North Bengal, Siliguri, Darjeeling, West Bengal, IndiaAbstract: Viral infections and pandemics result in millions of deaths worldwide each year. Viruses exploit host cellular processes, not only to gain entry and to deliver their genetic cargo, but also to counteract and use host immune defenses. To this end, a variety of ingenious strategies have evolved in viruses that involve fusion between virus and host membranes, channel formation through the host plasma membranes, disruption of the membrane vesicles, or a combination of these events. The entry and infection pathways of virus are thus largely defined by the interactions between virus particles and their cell surface and cytoplasmic receptors. A thorough analysis of virus–host interactomes may reveal novel mechanisms in virus entry, virus infection, and pathogenic strategies to modulate host metabolic pathways. The study of viral entry, infection, and pathogenesis has evolved over a long period. A host of next-generation technological advancements in this field has been discussed in this review.Keywords: RNA interference, high-throughput, bioinformatics, viral entry, viral infection, virus–host interactions

  5. Impregnating Coal With Calcium Carbonate

    Science.gov (United States)

    Sharma, Pramod K.; Voecks, Gerald E.; Gavalas, George R.

    1991-01-01

    Relatively inexpensive process proposed for impregnating coal with calcium carbonate to increase rates of gasification and combustion of coal and to reduce emission of sulfur by trapping sulfur in calcium sulfide. Process involves aqueous-phase reactions between carbon dioxide (contained within pore network of coal) and calcium acetate. Coal impregnated with CO2 by exposing it to CO2 at high pressure.

  6. Acidosis and Urinary Calcium Excretion

    DEFF Research Database (Denmark)

    Alexander, R Todd; Cordat, Emmanuelle; Chambrey, Régine;

    2016-01-01

    Metabolic acidosis is associated with increased urinary calcium excretion and related sequelae, including nephrocalcinosis and nephrolithiasis. The increased urinary calcium excretion induced by metabolic acidosis predominantly results from increased mobilization of calcium out of bone and...... renal tubule and then discuss why not all gene defects that cause renal tubular acidosis are associated with hypercalciuria and nephrocalcinosis....

  7. Direct Imaging of Hippocampal Epileptiform Calcium Motifs Following Kainic Acid Administration in Freely Behaving Mice.

    Science.gov (United States)

    Berdyyeva, Tamara K; Frady, E Paxon; Nassi, Jonathan J; Aluisio, Leah; Cherkas, Yauheniya; Otte, Stephani; Wyatt, Ryan M; Dugovic, Christine; Ghosh, Kunal K; Schnitzer, Mark J; Lovenberg, Timothy; Bonaventure, Pascal

    2016-01-01

    Prolonged exposure to abnormally high calcium concentrations is thought to be a core mechanism underlying hippocampal damage in epileptic patients; however, no prior study has characterized calcium activity during seizures in the live, intact hippocampus. We have directly investigated this possibility by combining whole-brain electroencephalographic (EEG) measurements with microendoscopic calcium imaging of pyramidal cells in the CA1 hippocampal region of freely behaving mice treated with the pro-convulsant kainic acid (KA). We observed that KA administration led to systematic patterns of epileptiform calcium activity: a series of large-scale, intensifying flashes of increased calcium fluorescence concurrent with a cluster of low-amplitude EEG waveforms. This was accompanied by a steady increase in cellular calcium levels (>5 fold increase relative to the baseline), followed by an intense spreading calcium wave characterized by a 218% increase in global mean intensity of calcium fluorescence (n = 8, range [114-349%], p wave had no consistent EEG phenotype and occurred before the onset of motor convulsions. Similar changes in calcium activity were also observed in animals treated with 2 different proconvulsant agents, N-methyl-D-aspartate (NMDA) and pentylenetetrazol (PTZ), suggesting the measured changes in calcium dynamics are a signature of seizure activity rather than a KA-specific pathology. Additionally, despite reducing the behavioral severity of KA-induced seizures, the anticonvulsant drug valproate (VA, 300 mg/kg) did not modify the observed abnormalities in calcium dynamics. These results confirm the presence of pathological calcium activity preceding convulsive motor seizures and support calcium as a candidate signaling molecule in a pathway connecting seizures to subsequent cellular damage. Integrating in vivo calcium imaging with traditional assessment of seizures could potentially increase translatability of pharmacological intervention, leading to

  8. Extracellular Ca2+ is a danger signal activating the NLRP3 inflammasome through G protein-coupled calcium sensing receptors

    DEFF Research Database (Denmark)

    Rossol, Manuela; Pierer, Matthias; Raulien, Nora; Quandt, Dagmar; Meusch, Undine; Rothe, Kathrin; Schubert, Kristin; Schöneberg, Torsten; Schaefer, Michael; Krügel, Ute; Smajilovic, Sanela; Bräuner-Osborne, Hans; Baerwald, Christoph; Wagner, Ulf

    2012-01-01

    calcium activates the NLRP3 inflammasome via stimulation of G protein-coupled calcium sensing receptors. Activation is mediated by signalling through the calcium-sensing receptor and GPRC6A via the phosphatidyl inositol/Ca(2+) pathway. The resulting increase in the intracellular calcium concentration...... this effect was inhibited in GPRC6A(-/-) mice. Our results demonstrate that G-protein-coupled receptors can activate the inflammasome, and indicate that increased extracellular calcium has a role as a danger signal and amplifier of inflammation....

  9. Role of Proteolipid Protein in HSV-1 Entry in Oligodendrocytic Cells

    Science.gov (United States)

    Bello-Morales, Raquel; Crespillo, Antonio Jesús; Praena, Beatriz; Tabarés, Enrique; Revilla, Yolanda; García, Elena; Fraile-Ramos, Alberto; Baron, Wia; Krummenacher, Claude; López-Guerrero, José Antonio

    2016-01-01

    Herpes simplex virus type 1 (HSV-1) has the ability to enter many different hosts and cell types by several strategies. This highly prevalent alphaherpesvirus can enter target cells using different receptors and different pathways: fusion at a neutral pH, low-pH-dependent and low-pH-independent endocytosis. Several cell receptors for viral entry have been described, but several observations suggest that more receptors for HSV-1 might exist. In this work, we propose a novel role for the proteolipid protein (PLP) in HSV-1 entry into the human oligodendrocytic cell line HOG. Cells transfected with PLP-EGFP showed an increase in susceptibility to HSV-1. Furthermore, the infection of HOG and HOG-PLP transfected cells with the R120vGF virus–unable to replicate in ICP4-defficient cells- showed an increase in viral signal in HOG-PLP, suggesting a PLP involvement in viral entry. In addition, a mouse monoclonal antibody against PLP drastically inhibited HSV-1 entry into HOG cells. PLP and virions colocalized in confocal immunofluorescence images, and in electron microscopy images, which suggest that PLP acts at the site of entry into HOG cells. Taken together these results suggest that PLP may be involved in HSV-1 entry in human oligodendrocytic cells. PMID:26807581

  10. Hydrogen sulfide raises cytosolic calcium in neurons through activation of L-type Ca2+ channels.

    Science.gov (United States)

    García-Bereguiaín, Miguel Angel; Samhan-Arias, Alejandro Khalil; Martín-Romero, Francisco Javier; Gutiérrez-Merino, Carlos

    2008-01-01

    Hydrogen sulfide (H(2)S) concentration can be maintained in cell cultures within the range reported for rat brain by repetitive pulses of sodium hydrogen sulfide. Less than 2 h exposure to H(2)S concentrations within 50 and 120 microM (i.e., within the upper segment of the reported physiological range of H(2)S in rat brain), produces a large shift of the intracellular calcium homeostasis in cerebellar granule neurons (CGN) in culture, leading to a large and sustained increase of cytosolic calcium concentration. Only 1 h exposure to H(2)S concentrations within 100 and 300 microM raises intracellular calcium to the neurotoxic range, with nearly 50% cell death after 2 h. L-type Ca(2+) channels antagonists nimodipine and nifedipine block both the H(2)S-induced rise of cytosolic calcium and cell death. The N-methyl-D-aspartate receptor antagonists (+)-MK-801 and DL-2-amino-5-phosphonovaleric acid afforded a nearly complete protection against H(2)S-induced CGN death and largely attenuated the rise of cytosolic calcium. Thus, H(2)S-induced rise of cytosolic calcium eventually reaches the neurotoxic cytosolic calcium range, leading to glutamate-induced excitotoxic CGN death. The authors conclude that H(2)S is a major modulator of calcium homeostasis in neurons as it induces activation of Ca(2+) entry through L-type Ca(2+) channels, and thereby of neuronal activity. PMID:17956188

  11. Modeling late entry bias in survival analysis.

    Science.gov (United States)

    Matsuura, Masaaki; Eguchi, Shinto

    2005-06-01

    In a failure time analysis, we sometimes observe additional study subjects who enter during the study period. These late entries are treated as left-truncated data in the statistical literature. However, with real data, there is a substantial possibility that the delayed entries may have extremely different hazards compared to the other standard subjects. We focus on a situation in which such entry bias might arise in the analysis of survival data. The purpose of the present article is to develop an appropriate methodology for making inference about data including late entries. We construct a model that includes parameters for the effect of delayed entry bias having no specification for the distribution of entry time. We also discuss likelihood inference based on this model and derive the asymptotic behavior of estimates. A simulation study is conducted for a finite sample size in order to compare the analysis results using our method with those using the standard method, where independence between entry time and failure time is assumed. We apply this method to mortality analysis among atomic bomb survivors defined in a geographical study region. PMID:16011705

  12. The role of Ca pathway in Cd uptake and translocation by the hyperaccumulator Sedum alfredii.

    Science.gov (United States)

    Lu, Lingli; Tian, Shengke; Zhang, Min; Zhang, Jie; Yang, Xiaoe; Jiang, Hong

    2010-11-15

    Effect of Ca on plant growth, Cd uptake and translocation in the hyperaccumulator Sedum alfredii was investigated, as to reveal the possible pathway of Cd entry into the plants system. High Ca increased plant growth under Cd stress after 7 d, and significantly affected the total Cd influx and translocation rate. Short-term kinetics of (109)Cd influx performed using radiotracers confirmed a significant inhibition of (109)Cd influx into the roots induced by high Ca. Under exposure of 5.0 mM Ca, K(m) of (109)Cd influx into roots was 2-fold higher in the hyperaccumulator, although the V(max) value remained at similar level, when compared with the treatments of 0.5 mM Ca. Calcium concentrations in xylem sap of the hyperaccumulator decreased with the increasing Cd levels and significant negative correlationship between the two elements was observed. However, increased xylem loading of Cd was observed in the hyperaccumulator in response to the increasing exogenous Ca level from 0.5 to 4.0 mM, but reverse effect was observed when higher Ca levels (8-32 mM) were presented in the solutions. These results suggest that Cd uptake and translocation in the hyperaccumulator S. alfredii plants is positively associated with Ca pathway. PMID:20674155

  13. The role of Ca pathway in Cd uptake and translocation by the hyperaccumulator Sedum alfredii

    Energy Technology Data Exchange (ETDEWEB)

    Lu Lingli, E-mail: linglilulu@gmail.com [MOE Key Laboratory of Environment Remediation and Ecosystem Health, College of Environmental and Resources Science, Zhejiang University, Huajiachi Campus, Hangzhou 310029 (China); Tian Shengke; Zhang Min; Zhang Jie [MOE Key Laboratory of Environment Remediation and Ecosystem Health, College of Environmental and Resources Science, Zhejiang University, Huajiachi Campus, Hangzhou 310029 (China); Yang Xiaoe, E-mail: xyang571@yahoo.com [MOE Key Laboratory of Environment Remediation and Ecosystem Health, College of Environmental and Resources Science, Zhejiang University, Huajiachi Campus, Hangzhou 310029 (China); Jiang Hong [MOE Key Laboratory of Environment Remediation and Ecosystem Health, College of Environmental and Resources Science, Zhejiang University, Huajiachi Campus, Hangzhou 310029 (China)

    2010-11-15

    Effect of Ca on plant growth, Cd uptake and translocation in the hyperaccumulator Sedum alfredii was investigated, as to reveal the possible pathway of Cd entry into the plants system. High Ca increased plant growth under Cd stress after 7 d, and significantly affected the total Cd influx and translocation rate. Short-term kinetics of {sup 109}Cd influx performed using radiotracers confirmed a significant inhibition of {sup 109}Cd influx into the roots induced by high Ca. Under exposure of 5.0 mM Ca, K{sub m} of {sup 109}Cd influx into roots was 2-fold higher in the hyperaccumulator, although the V{sub max} value remained at similar level, when compared with the treatments of 0.5 mM Ca. Calcium concentrations in xylem sap of the hyperaccumulator decreased with the increasing Cd levels and significant negative correlationship between the two elements was observed. However, increased xylem loading of Cd was observed in the hyperaccumulator in response to the increasing exogenous Ca level from 0.5 to 4.0 mM, but reverse effect was observed when higher Ca levels (8-32 mM) were presented in the solutions. These results suggest that Cd uptake and translocation in the hyperaccumulator S. alfredii plants is positively associated with Ca pathway.

  14. A sophisticated network of signaling pathways regulates stomatal defenses to bacterial pathogens.

    Science.gov (United States)

    Arnaud, Dominique; Hwang, Ildoo

    2015-04-01

    Guard cells are specialized cells forming stomatal pores at the leaf surface for gas exchanges between the plant and the atmosphere. Stomata have been shown to play an important role in plant defense as a part of the innate immune response. Plants actively close their stomata upon contact with microbes, thereby preventing pathogen entry into the leaves and the subsequent colonization of host tissues. In this review, we present current knowledge of molecular mechanisms and signaling pathways implicated in stomatal defenses, with particular emphasis on plant-bacteria interactions. Stomatal defense responses begin from the perception of pathogen-associated molecular patterns (PAMPs) and activate a signaling cascade involving the production of secondary messengers such as reactive oxygen species, nitric oxide, and calcium for the regulation of plasma membrane ion channels. The analyses on downstream molecular mechanisms implicated in PAMP-triggered stomatal closure have revealed extensive interplays among the components regulating hormonal signaling pathways. We also discuss the strategies deployed by pathogenic bacteria to counteract stomatal immunity through the example of the phytotoxin coronatine. PMID:25661059

  15. Optimal firm growth under the threat of entry

    OpenAIRE

    Peter M. Kort; Wrzaczek, Stefan

    2015-01-01

    The paper studies the incumbent-entrant problem in a fully dynamic setting. We find that under an open-loop information structure the incumbent anticipates entry by overinvesting, whereas in the Markov perfect equilibrium the incumbent slightly underinvests in the period before the entry. The entry cost level where entry accommodation passes into entry deterrence is lower in the Markov perfect equilibrium. Further we find that the incumbent’s capital stock level needed to deter entry is hump ...

  16. Regulation of Arterial Tone by Activation of Calcium-Dependent Potassium Channels

    Science.gov (United States)

    Brayden, Joseph E.; Nelson, Mark T.

    1992-04-01

    Blood pressure and tissue perfusion are controlled in part by the level of intrinsic (myogenic) vascular tone. However, many of the molecular determinants of this response are unknown. Evidence is now presented that the degree of myogenic tone is regulated in part by the activation of large-conductance calcium-activated potassium channels in arterial smooth muscle. Tetraethylammonium ion (TEA^+) and charybdotoxin (CTX), at concentrations that block calcium-activated potassium channels in smooth muscle cells isolated from cerebral arteries, depolarized and constricted pressurized cerebral arteries with myogenic tone. Both TEA^+ and CTX had little effect on arteries when intracellular calcium was reduced by lowering intravascular pressure or by blocking calcium channels. Elevation of intravascular pressure through membrane depolarization and an increase in intracellular calcium may activate calcium-activated potassium channels. Thus, these channels may serve as a negative feedback pathway to control the degree of membrane depolarization and vasoconstriction.

  17. Individual aggregates of amyloid beta induce temporary calcium influx through the cell membrane of neuronal cells

    Science.gov (United States)

    Drews, Anna; Flint, Jennie; Shivji, Nadia; Jönsson, Peter; Wirthensohn, David; De Genst, Erwin; Vincke, Cécile; Muyldermans, Serge; Dobson, Chris; Klenerman, David

    2016-01-01

    Local delivery of amyloid beta oligomers from the tip of a nanopipette, controlled over the cell surface, has been used to deliver physiological picomolar oligomer concentrations to primary astrocytes or neurons. Calcium influx was observed when as few as 2000 oligomers were delivered to the cell surface. When the dosing of oligomers was stopped the intracellular calcium returned to basal levels or below. Calcium influx was prevented by the presence in the pipette of the extracellular chaperone clusterin, which is known to selectively bind oligomers, and by the presence a specific nanobody to amyloid beta. These data are consistent with individual oligomers larger than trimers inducing calcium entry as they cross the cell membrane, a result supported by imaging experiments in bilayers, and suggest that the initial molecular event that leads to neuronal damage does not involve any cellular receptors, in contrast to work performed at much higher oligomer concentrations. PMID:27553885

  18. Astrocyte glycogenolysis is triggered by store-operated calcium entry and provides metabolic energy for cellular calcium homeostasis

    DEFF Research Database (Denmark)

    Müller, Margit S; Fox, Rebecca; Schousboe, Arne;

    2014-01-01

    Astrocytic glycogen, the only storage form of glucose in the brain, has been shown to play a fundamental role in supporting learning and memory, an effect achieved by providing metabolic support for neurons. We have examined the interplay between glycogenolysis and the bioenergetics of astrocytic...... glycogenolysis. We also provide first evidence for a new functional role of brain glycogen, in providing local ATP to SERCA, thus establishing the bioenergetic basis for astrocytic Ca(2+) signaling. This mechanism could offer a novel explanation for the impact of glycogen on learning and memory. GLIA 2014;62:526-534....

  19. Calcium and calcitonin responses to calcium infusion in type I diabetes mellitus.

    OpenAIRE

    Amado, J. A.; C. Gomez; Obaya, S.; Otero, M; Gonzalez-Macias, J

    1987-01-01

    We studied calcium and calcium and calcitonin responses to intravenous calcium infusion (3 mg of elemental calcium/kg of body weight in 10 minutes) in 21 type I diabetic males and 17 age-matched normal males. Baseline total calcium, parathyroid hormone and calcitonin levels were normal in the diabetic group, but ionized calcium was lowered. Cortical bone status and osteocalcin levels were normal, suggesting a normal osteoblastic function. Total calcium and ionized calcium responses to calcium...

  20. Calcium and ROS: A mutual interplay.

    Science.gov (United States)

    Görlach, Agnes; Bertram, Katharina; Hudecova, Sona; Krizanova, Olga

    2015-12-01

    Calcium is an important second messenger involved in intra- and extracellular signaling cascades and plays an essential role in cell life and death decisions. The Ca(2+) signaling network works in many different ways to regulate cellular processes that function over a wide dynamic range due to the action of buffers, pumps and exchangers on the plasma membrane as well as in internal stores. Calcium signaling pathways interact with other cellular signaling systems such as reactive oxygen species (ROS). Although initially considered to be potentially detrimental byproducts of aerobic metabolism, it is now clear that ROS generated in sub-toxic levels by different intracellular systems act as signaling molecules involved in various cellular processes including growth and cell death. Increasing evidence suggests a mutual interplay between calcium and ROS signaling systems which seems to have important implications for fine tuning cellular signaling networks. However, dysfunction in either of the systems might affect the other system thus potentiating harmful effects which might contribute to the pathogenesis of various disorders. PMID:26296072

  1. DISTILLATION OF CALCIUM

    Science.gov (United States)

    Barton, J.

    1954-07-27

    This invention relates to an improvement in the process for the purification of caicium or magnesium containing an alkali metal as impurity, which comprises distiiling a batch of the mixture in two stages, the first stage distillation being carried out in the presence of an inert gas at an absolute pressure substantially greater than the vapor pressure of calcium or maguesium at the temperature of distillation, but less than the vaper pressure at that temperature of the alkali metal impurity so that only the alkali metal is vaporized and condensed on a condensing surface. A second stage distilso that substantially only the calcium or magnesium distills under its own vapor pressure only and condenses in solid form on a lower condensing surface.

  2. Advances in spacecraft atmospheric entry guidance

    Science.gov (United States)

    Benito Manrique, Joel

    In order to advance entry guidance technology two different research areas have been explored with the objective of increasing the reachable landing area and the landing accuracy for future Mars missions. Currently only the northern hemisphere of Mars is available for landing due to its low elevation. Only low elevation landing sites have the necessary atmospheric density to allow landing using current Entry, Descent and Landing (EDL) technology. In order to reach most of the Ancient Highlands, the majority of the southern hemisphere, advanced EDL technology is needed in multiple fields, including entry guidance. The first research area is the definition and applications of reachable and controllable sets for entry. The definition of the reachable and controllable sets provides a framework for the study of the capabilities of an entry vehicle in a given planet. Reachable and controllable sets can be used to comprehensively characterize the envelope of trajectories that a vehicle can fly, the sites it can reach and the entry states that can be accommodated. The sets can also be used for the evaluation of trajectory planning algorithms and to assist in the selection of the entry or landing sites. In essence, the reachable and controllable sets offer a powerful vehicle and trajectory analysis and design framework that allows for better mission design choices. In order to illustrate the use of the sets, they are computed for a representative Mars mission using two different vehicle configurations. The sets characterize the impact of the vehicle configuration on the entry capability. Furthermore, the sets are used to find the best skip-entry trajectory for a return from the Moon mission, highlighting the utility of the sets in atmospheric maneuvers other than entry. The second research area is the development of the components of an entry guidance algorithm that allow high elevation landing and provide as well high landing accuracy. The approach taken follows the

  3. Foreign Entry and Heterogeneous Growth of Firms

    DEFF Research Database (Denmark)

    Deng, Paul Duo; Jefferson, Gary H.

    We adopt the framework of Schumpeterian creative destruction formalized by Aghion et al. (2009) to analyze the impact of foreign entry on the productivity growth of domestic firms. In the face of foreign entry, domestic firms exhibit heterogeneous patterns of growth depending on their technological...... distance from foreign firms. Domestic firms with smaller technological distance from their foreign counterparts tend to experience faster productivity growth, while firms with larger technological distance tend to lag further behind. We test this hypothesis using a unique firm-level data of Chinese...... manufacturing. Our empirical results confirm that foreign entry indeed generates strong heterogeneous growth patterns among domestic firms....

  4. Physical security workshop summary: entry control

    International Nuclear Information System (INIS)

    Entry control hardware has been used extensively in the past to assist security forces in separating the authorized from the unauthorized at the plant perimeter. As more attention is being focused on the insider threat, these entry control elements are being used to extend the security inspectors' presence into the plant by compartmentalizing access and monitoring vital components. This paper summarizes the experiences expressed by the participants at the March 16 to 19, 1982 INMM Physical Protection Workshop in utilizing access control and contraband detection hardware for plant wide entry control applications

  5. Entry Regulation under Asymmetric Information about Demand

    Directory of Open Access Journals (Sweden)

    Paula Sarmento

    2010-01-01

    Full Text Available We investigate how an incumbent firm can use the regulatory policy about entry and the informational advantage to protect his market position. This question is studied through the construction of a signalling game where we assume that the regulator has less information about demand than the firms. We conclude that there is a pooling equilibrium and partially separating equilibria in which entry is deterred and, if demand is high, there will be insufficient entry. The final effect on welfare depends on the tradeoff between short-run benefits (lower price and long-run losses (weaker competition.

  6. Texting while driving: is speech-based text entry less risky than handheld text entry?

    Science.gov (United States)

    He, J; Chaparro, A; Nguyen, B; Burge, R J; Crandall, J; Chaparro, B; Ni, R; Cao, S

    2014-11-01

    Research indicates that using a cell phone to talk or text while maneuvering a vehicle impairs driving performance. However, few published studies directly compare the distracting effects of texting using a hands-free (i.e., speech-based interface) versus handheld cell phone, which is an important issue for legislation, automotive interface design and driving safety training. This study compared the effect of speech-based versus handheld text entries on simulated driving performance by asking participants to perform a car following task while controlling the duration of a secondary text-entry task. Results showed that both speech-based and handheld text entries impaired driving performance relative to the drive-only condition by causing more variation in speed and lane position. Handheld text entry also increased the brake response time and increased variation in headway distance. Text entry using a speech-based cell phone was less detrimental to driving performance than handheld text entry. Nevertheless, the speech-based text entry task still significantly impaired driving compared to the drive-only condition. These results suggest that speech-based text entry disrupts driving, but reduces the level of performance interference compared to text entry with a handheld device. In addition, the difference in the distraction effect caused by speech-based and handheld text entry is not simply due to the difference in task duration. PMID:25089769

  7. Models of calcium signalling

    CERN Document Server

    Dupont, Geneviève; Kirk, Vivien; Sneyd, James

    2016-01-01

    This book discusses the ways in which mathematical, computational, and modelling methods can be used to help understand the dynamics of intracellular calcium. The concentration of free intracellular calcium is vital for controlling a wide range of cellular processes, and is thus of great physiological importance. However, because of the complex ways in which the calcium concentration varies, it is also of great mathematical interest.This book presents the general modelling theory as well as a large number of specific case examples, to show how mathematical modelling can interact with experimental approaches, in an interdisciplinary and multifaceted approach to the study of an important physiological control mechanism. Geneviève Dupont is FNRS Research Director at the Unit of Theoretical Chronobiology of the Université Libre de Bruxelles;Martin Falcke is head of the Mathematical Cell Physiology group at the Max Delbrück Center for Molecular Medicine, Berlin;Vivien Kirk is an Associate Professor in the Depar...

  8. Reverse calcium affinity purification of Fab with calcium derivatized hydroxyapatite

    OpenAIRE

    Gagnon, Pete; Cheung, Chia-wei; Yazaki, Paul J.

    2009-01-01

    This study introduces the application of calcium-derivatized hydroxyapatite for purification of Fab. Fab binds to native hydroxyapatite but fails to bind to the calcium derivatized form. IgG, Fc, and most other protein contaminants bind to the calcium form. This supports Fab purification by a simple flow-through method that achieves greater than 95% purity from papain digests and mammalian cell culture supernatants. Alternatively, Fab can be concentrated on native hydroxyapatite then eluted s...

  9. The Effects of Entry in Bilateral Oligopoly

    Directory of Open Access Journals (Sweden)

    Alex Dickson

    2013-06-01

    Full Text Available The purpose of this paper is to study the effects of entry into the market for a single commodity in which both sellers and buyers are permitted to interact strategically. With the inclusion of an additional seller, the market is quasi-competitive: the price falls and volume of trade increases, as expected. However, contrary to the conventional wisdom, existing sellers’ payoffs may increase. The conditions under which entry by new sellers raises the equilibrium payoffs of existing sellers are derived. These depend in an intuitive way on the elasticity of a strategic analog of demand and the market share of existing sellers, and encompass entirely standard economic environments. Similar results are derived relating to the entry of additional buyers and the effects of entry on both sides of the market are investigated.

  10. Entry tank calibration in TOR pilot plant

    International Nuclear Information System (INIS)

    The objective of this communication is the description of calibration measurements used for determining the uranium and plutonium mass entry in the fast neutron fuel reprocessing pilot plant (TOR) of Marcoule

  11. Adaptive Text Entry for Mobile Devices

    DEFF Research Database (Denmark)

    Proschowsky, Morten Smidt

    for mobile devices and a framework for adaptive context-aware language models. Based on analysis of current text entry methods, the requirements to the new text entry methods are established. Transparent User guided Prediction (TUP) is a text entry method for devices with one dimensional touch input....... It can be touch sensitive wheels, sliders or similar input devices. The interaction design of TUP is done with a combination of high level task models and low level models of human motor behaviour. Three prototypes of TUP are designed and evaluated by more than 30 users. Observations from the...... evaluations are used to improve the models of human motor behaviour. TUP-Key is a variant of TUP, designed for 12 key phone keyboards. It is introduced in the thesis but has not been implemented or evaluated. Both text entry methods support adaptive context-aware language models. YourText is a framework for...

  12. Aerocapture Inflatable Decelerator for Planetary Entry

    Science.gov (United States)

    Reza, Sajjad; Hund, Richard; Kustas, Frank; Willcockson, William; Songer, Jarvis; Brown, Glen

    2007-01-01

    Forward Attached Inflatable Decelerators, more commonly known as inflatable aeroshells, provide an effective, cost efficient means of decelerating spacecrafts by using atmospheric drag for aerocapture or planetary entry instead of conventional liquid propulsion deceleration systems. Entry into planetary atmospheres results in significant heating and aerodynamic pressures which stress aeroshell systems to their useful limits. Incorporation of lightweight inflatable decelerator surfaces with increased surface-area footprints provides the opportunity to reduce heat flux and induced temperatures, while increasing the payload mass fraction. Furthermore, inflatable aeroshell decelerators provide the needed deceleration at considerably higher altitudes and Mach numbers when compared with conventional rigid aeroshell entry systems. Inflatable aeroshells also provide for stowage in a compact space, with subsequent deployment of a large-area, lightweight heatshield to survive entry heating. Use of a deployable heatshield decelerator enables an increase in the spacecraft payload mass fraction and may eliminate the need for a spacecraft backshell.

  13. Market entry strategies into the BRIC countries

    DEFF Research Database (Denmark)

    Boyd, Britta; Dyhr Ulrich, Anna Marie

    2014-01-01

    Based on a sample of 177 exporting SMEs, this study investigates what market entry strategy is used by Danish family and non-family businesses. From a resource-based view, three critical internal factors (risk, flexibility and control) affecting the entry mode choice into the BRIC markets...... compared to non-family firms. Furthermore, the Danish exporters regarded China as being the most established of the four BRIC markets which could be seen in their willingness to use high control entry modes in China. Finally, non-family firms are more concerned about higher flexibility and lower control...... when entering the BRIC markets. In contrast, family firms choose high commitment entry modes which involve high risk and low flexibility when entering the BRIC markets. Further implications discuss the suitability of export strategies to BRIC markets for managers of Danish family and non-family firms....

  14. Border Crossing/Entry Data - Boarder Crossing

    Data.gov (United States)

    Department of Transportation — Border Crossing/Entry Data provides summary statistics for incoming crossings at the U.S.-Canadian and the U.S.-Mexican border at the port level. Data are available...

  15. Predecessors of Double-Entry Accounting

    OpenAIRE

    Mykhaylo Kuter; Maryna Gurskaya; Artem Musaelyan

    2013-01-01

    The article covers analysis of some historically significant issues of accounting development in the home-country of contemporary accounting made with reference to the archived materials found in Italy. In particular, the issue of purpose and order of taking entries in the book titled 'RICORDANZE' ('Memorials') has been considered. Resulting from the analysis done, the significance has been grounded for keeping accounting records which do not subject to double-entry principle thus being busin...

  16. Developing Quantitative Models for Auditing Journal Entries

    OpenAIRE

    Argyrou, Argyris

    2013-01-01

    The thesis examines how the auditing of journal entries can detect and prevent financial statement fraud. Financial statement fraud occurs when an intentional act causes financial statements to be materially misstated. Although it is not a new phenomenon, financial statement fraud has attracted much publicity in the wake of numerous cases of financial malfeasance (e.g. ENRON, WorldCom). Existing literature has provided limited empirical evidence on the link between auditing journal entrie...

  17. Entry and exit decisions under uncertainty

    DEFF Research Database (Denmark)

    Kongsted, Hans Christian

    1996-01-01

    This paper establishes the general deterministic limit that corresponds to Dixit's model of entry and exit decisions under uncertainty. The interlinked nature of decisions is shown to be essential also in the deterministic limit. A numerical example illustrates the result......This paper establishes the general deterministic limit that corresponds to Dixit's model of entry and exit decisions under uncertainty. The interlinked nature of decisions is shown to be essential also in the deterministic limit. A numerical example illustrates the result...

  18. Market Structure and Entry: Where's the Beef?.

    OpenAIRE

    Toivanen, O.; Waterson, M

    2001-01-01

    We study the effects of market structure on entry using data from the UK fast food (counter-service burger)industry over the years 1991-1995. Over this period, the market can be characterized as a duopoly. We find that market structure matters greatly: for both firms, rival presence increases the probability of entry. We control for market specific time-invariant unobservable and their correlation with existing outlets of both firms through a variety of methods.

  19. Entry Modes for British MNCs into China

    OpenAIRE

    Phillips, Alexander

    2013-01-01

    China has undergone massive economic reforms and institutional changes over the last 3 decades. Increasingly liberalized government regulations and the opening up of the Chinese market have attracted British MNCs to enter into this ‘dream market’. This paper seeks to primarily explore the factors that affect the entry mode selection of British MNCs. It will also seek to investigate how the current institutional environment affects entry mode selection. This paper uses a case study method to a...

  20. Entry and Exit in a Liberalised Market

    OpenAIRE

    Maria José Gil-Moltó; Claudio A. Piga

    2007-01-01

    We analyse the entry and exit activity in the UK airline markets in the post-liberalisation period and study the differential traits between traditional and low cost carriers. Alongside with the characteristics traditionally highlighted as determinants of entry (e.g., airport presence and network economies), we find that the existence of charter or seasonal operators, product differentiation opportunities and the level of quality provided by the incumbents are also relevant in explaining entr...

  1. Global Strategy and Multinationals' Entry Mode Choice

    OpenAIRE

    W. Chan Kim; Peter Hwang

    1992-01-01

    This paper makes a case directed towards establishing the importance of global strategic considerations in choosing multinationals' entry mode. Specifically, it is our contention that beyond the environmental and transaction-specific factors well established in the literature to affect the entry mode decision, we should also consider the strategic relationship a multinational envisages between its operations across borders in reaching this decision. After incorporating various global strategi...

  2. Entry modes of European firms in Vietnam

    OpenAIRE

    Daniel Simonet

    2012-01-01

    Purpose: The purpose of the paper is to explore the entry modes of EU firms setting up operations in Vietnam. Design/methodology/approach: we use a case study approach on Haymarket, Cadbury, Creative Education, Fairchild, Aventis and Artemisinin and Farming International using interviews from managerial professionals in Vietnam. Findings: Despite the fact that Vietnam has been opening up for more than 20 years, licensing is the preferred entry mode because of the risks involved in ventur...

  3. Double Entry in Accounting of Small Businesses

    OpenAIRE

    Gogol Tatyana A.

    2013-01-01

    The article states that a separate category of small businesses (starting from 2011) acquired the right to conduct simplified accounting of income and expenses without application of the plan of accounts and method of double entry. Analysis of literature sources allowed drawing a conclusion that it is impossible to imagine development of accounting without the use of the method of double entry and appearance of various theories regarding the reasons of its appearance. Having analysed methods ...

  4. Glycochenodeoxycholic acid inhibits calcium phosphate precipitation in vitro by preventing the transformation of amorphous calcium phosphate to calcium hydroxyapatite.

    OpenAIRE

    Qiu, S M; Wen, G.; Hirakawa, N; Soloway, R D; Hong, N K; Crowther, R S

    1991-01-01

    Calcium hydroxyapatite can be a significant component of black pigment gallstones. Diverse molecules that bind calcium phosphate inhibit hydroxyapatite precipitation. Because glycine-conjugated bile acids, but not their taurine counterparts, bind calcium phosphate, we studied whether glycochenodeoxycholic acid inhibits calcium hydroxyapatite formation. Glycochenodeoxycholic acid (2 mM) totally inhibited transformation of amorphous calcium phosphate microprecipitates to macroscopic crystalline...

  5. Strontium and calcium determination in sea fishes in neighborhood of Angra nuclear power plant

    International Nuclear Information System (INIS)

    Strontium-90 is an important radionuclide present in the liquid effluents of the Angra Nuclear Power Plant, located in the coastline of Rio de Janeiro State. It has a long effective half-life, easy entry into food chain due to its chemical similarity to calcium and stays for a long time in solution. With the aim of calculating the concentration factor (CF) for 90 Sr and observed ratio (OR) in the most abundant local fish, it was determined the strontium and calcium content in the edible fraction of nine species and in sea water by atomic absorption spectrophotometry. (author)

  6. Cytosolic organelles shape calcium signals and exo-endocytotic responses of chromaffin cells.

    Science.gov (United States)

    García, Antonio G; Padín, Fernando; Fernández-Morales, José C; Maroto, Marcos; García-Sancho, Javier

    2012-01-01

    The concept of stimulus-secretion coupling was born from experiments performed in chromaffin cells 50 years ago. Stimulation of these cells with acetylcholine enhances calcium (Ca(2+)) entry and this generates a transient elevation of the cytosolic Ca(2+) concentration ([Ca(2+)](c)) that triggers the exocytotic release of catecholamines. The control of the [Ca(2+)](c) signal is complex and depends on various classes of plasmalemmal calcium channels, cytosolic calcium buffers, the uptake and release of Ca(2+) from cytoplasmic organelles, such as the endoplasmic reticulum, mitochondria, chromaffin vesicles and the nucleus, and Ca(2+) extrusion mechanisms, such as the plasma membrane Ca(2+)-stimulated ATPase, and the Na(+)/Ca(2+) exchanger. Computation of the rates of Ca(2+) fluxes between the different cell compartments support the proposal that the chromaffin cell has developed functional calcium tetrads formed by calcium channels, cytosolic calcium buffers, the endoplasmic reticulum, and mitochondria nearby the exocytotic plasmalemmal sites. These tetrads shape the Ca(2+) transients occurring during cell activation to regulate early and late steps of exocytosis, and the ensuing endocytotic responses. The different patterns of catecholamine secretion in response to stress may thus depend on such local [Ca(2+)](c) transients occurring at different cell compartments, and generated by redistribution and release of Ca(2+) by cytoplasmic organelles. In this manner, the calcium tetrads serve to couple the variable energy demands due to exo-endocytotic activities with energy production and protein synthesis. PMID:22209033

  7. Calcium – how and why?

    Indian Academy of Sciences (India)

    J K Jaiswal

    2001-09-01

    Calcium is among the most commonly used ions, in a multitude of biological functions, so much so that it is impossible to imagine life without calcium. In this article I have attempted to address the question as to how calcium has achieved this status with a brief mention of the history of calcium research in biology. It appears that during the origin and early evolution of life the Ca2+ ion was given a unique opportunity to be used in several biological processes because of its unusual physical and chemical properties.

  8. Calcium addition in straw gasification

    DEFF Research Database (Denmark)

    Risnes, H.; Fjellerup, Jan Søren; Henriksen, Ulrik Birk; Moilanen, A.; Norby, P.; Papadakis, K.; Posselt, D.; Sørensen, L. H.

    2003-01-01

    The present work focuses on the influence of calcium addition in gasification. The inorganic¿organic element interaction as well as the detailed inorganic¿inorganic elements interaction has been studied. The effect of calcium addition as calcium sugar/molasses solutions to straw significantly...... affected the ash chemistry and the ash sintering tendency but much less the char reactivity. Thermo balance test are made and high-temperature X-ray diffraction measurements are performed, the experimental results indicate that with calcium addition major inorganic¿inorganic reactions take place very late...

  9. Calcium Phosphate Biomaterials: An Update

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    Current calcium phosphate (CaP) biomaterials for bone repair, substitution, augmentation and regeneration include hydroxyapatite ( HA ) from synthetic or biologic origin, beta-tricalcium phosphate ( β-TCP ) , biphasic calcium phosphate (BCP), and are available as granules, porous blocks, components of composites (CaP/polymer) cements, and as coatings on orthopedic and dental implants. Experimental calcium phosphate biomaterials include CO3- and F-substituted apatites, Mg-and Zn-substituted β-TCP, calcium phosphate glasses. This paper is a brief review of the different types of CaP biomaterials and their properties such as bioactivity, osteoconductivity, osteoinductivity.

  10. Scientific Opinion on the risk of entry of Aethina tumida and Tropilaelaps spp. in the EU

    Directory of Open Access Journals (Sweden)

    EFSA Panel on Animal Health and Welfare (AHAW

    2013-03-01

    Full Text Available Small hive beetle (SHB and Tropilaelaps are bee diseases considered exotic in the EU. SHBis a flying coleopteran that can be attracted to the odours of bees and bee products. In addition, SHB can survive and reproduce on a variety of ripe fruits. Tropilaelaps is an ectoparasite that does not survive long without honey bee brood and cannot fly by itself. The methodology used to assess the risk of entry of these pests in this scientific opinion was adapted from a pest risk assessment for entry used in the field of plant health. A qualitative risk assessment was performed taking into account current legislation but excluding the implementation of risk reduction options. This approach allowed the assessment of the worst case scenario for each risk factor. The risk pathways with a high risk of pest entry are ‘import of bee products (use in apiculture’ for SHB and ‘accidental import of bees’ (unintended presence of bees in a non-bee consignment for both pests. The other risk pathways are associated with a moderate or low risk of SHB or Tropilaelaps entry into the risk assessment area. Risk reduction options were assessed separately from the risk assessment. Examples of risk reduction options with a high effectiveness and a high technical feasibility are the use of health certificates to guarantee pest freedom of consignments and keeping consignments without honey bee brood. Options with a high effectiveness and technical feasibility were identified in all risk pathways except ‘accidental import of bees’ and ‘dispersal of the pest via natural means and/or flight’. The AHAW Panel identified the need for validated rapid detection methods and for handling and sampling of imported bees in insect-proof environments. Education and training could help to monitor the pest distribution and to prevent pest entry by improving awareness, skills and expertise.

  11. 21 CFR 573.240 - Calcium periodate.

    Science.gov (United States)

    2010-04-01

    ... with calcium hydroxide or calcium oxide to form a substance consisting of not less than 60 percent by... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Calcium periodate. 573.240 Section 573.240 Food... Additive Listing § 573.240 Calcium periodate. The food additive calcium periodate may be safely used...

  12. 21 CFR 573.260 - Calcium silicate.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Calcium silicate. 573.260 Section 573.260 Food and... Listing § 573.260 Calcium silicate. Calcium silicate, including synthetic calcium silicate, may be safely used as an anticaking agent in animal feed, provided that the amount of calcium silicate does...

  13. Calcium measurement methods

    Directory of Open Access Journals (Sweden)

    CarloAlberto Redi

    2010-09-01

    Full Text Available Rightly stressed by prof. Wolfgang Walz in the Preface to the series Neuromethods series, the “careful application of methods is probably the most important step in the process of scientific inquiry”. Thus, I strongly suggest to all those interested in calcium signaling and especially to the new-comers in the hot topic of neuroscience (which has so much space even in science-society debate for its implications in legal issues and in the judge-decision process to take profit from this so well edited book. I am saying this since prof. Verkhratsky and prof. Petersen......

  14. Recent Observations on Australian Bat Lyssavirus Tropism and Viral Entry

    Directory of Open Access Journals (Sweden)

    Dawn L. Weir

    2014-02-01

    Full Text Available Australian bat lyssavirus (ABLV is a recently emerged rhabdovirus of the genus lyssavirus considered endemic in Australian bat populations that causes a neurological disease in people indistinguishable from clinical rabies. There are two distinct variants of ABLV, one that circulates in frugivorous bats (genus Pteropus and the other in insectivorous microbats (genus Saccolaimus. Three fatal human cases of ABLV infection have been reported, the most recent in 2013, and each manifested as acute encephalitis but with variable incubation periods. Importantly, two equine cases also arose recently in 2013, the first occurrence of ABLV in a species other than bats or humans. Similar to other rhabdoviruses, ABLV infects host cells through receptor-mediated endocytosis and subsequent pH-dependent fusion facilitated by its single fusogenic envelope glycoprotein (G. Recent studies have revealed that proposed rabies virus (RABV receptors are not sufficient to permit ABLV entry into host cells and that the unknown receptor is broadly conserved among mammalian species. However, despite clear tropism differences between ABLV and RABV, the two viruses appear to utilize similar endocytic entry pathways. The recent human and horse infections highlight the importance of continued Australian public health awareness of this emerging pathogen.

  15. Calcium-dependent activation of Pyk2 by hypoxia.

    Science.gov (United States)

    Beitner-Johnson, Dana; Ferguson, Tsuneo; Rust, Randy T; Kobayashi, Shuichi; Millhorn, David E

    2002-02-01

    The Pyk2 tyrosine kinase can be activated by both calcium-dependent and calcium-independent mechanisms. Exposure to moderate hypoxia (5% O(2)) induced a rapid and persistent tyrosine phosphorylation of Pyk2 in pheochromocytoma (PC12) cells. Hypoxia and KCl-depolarization increased the phosphotyrosine content of Pyk2 by twofold and fourfold, respectively. Both of these effects were abolished in the absence of extracellular calcium. There was a modest activation of MAPK in parallel with the onset of Pyk2 phosphorylation. However, there was no detectable activation of either JNK or c-src, two other known downstream targets of Pyk2. Thus, exposure to hypoxia may selectively target specific subsets of Pyk2 signalling pathways. PMID:11781137

  16. STIM and calcium channel complexes in cancer.

    Science.gov (United States)

    Jardin, Isaac; Rosado, Juan A

    2016-06-01

    The ion Ca(2+) is a ubiquitous second messenger that mediates a variety of cellular functions. Dysfunction of the mechanisms involved in Ca(2+) homeostasis underlies a number of pathological processes, including cancer. Store-operated Ca(2+) entry (SOCE) is a major mechanism for Ca(2+) entry modulated by the intracellular Ca(2+) stores. The Ca(2+)-selective store-operated current (ICRAC) is mediated by the endoplasmic reticulum (ER) Ca(2+) sensor STIM1 and the store-operated Ca(2+) (SOC) channel Orai1, while other non-selective cation currents (ISOC) involves the participation of members of the canonical transient receptor potential (TRPC) channel family, including TRPC1. Distinct isoforms of the key components of SOCE have been described in mammalian cells, STIM1 and 2, Orai1-3 and TRPC1-7. In cancer cells, SOCE has been reported to play an important role in cell cycle progression and proliferation, migration, metastasis and evasion of apoptosis. Changes in the expression of the key elements of SOCE and Ca(2+) homeostasis remodeling have been account to play important roles in the phenotypic changes observed in transformed cells. Despite there are differences in the expression level of the molecular components of SOCE, as well as in the relevance of the STIM, Orai and TRPC isoforms in SOCE and tumorigenesis among cancer cell types, there is a body of evidence supporting an important role for SOCE underlying the phenotypic modifications of cancer cells that propose STIM and the SOC channels as suitable candidate targets for future prognostic or therapeutic strategies. This article is part of a Special Issue entitled: Calcium and Cell Fate. Guest Editors: Jacques Haiech, Claus Heizmann, Joachim Krebs, Thierry Capiod and Olivier Mignen. PMID:26455959

  17. Extracellular calcium sensing and extracellular calcium signaling

    Science.gov (United States)

    Brown, E. M.; MacLeod, R. J.; O'Malley, B. W. (Principal Investigator)

    2001-01-01

    , localized changes in Ca(o)(2+) within the ECF can originate from several mechanisms, including fluxes of calcium ions into or out of cellular or extracellular stores or across epithelium that absorb or secrete Ca(2+). In any event, the CaR and other receptors/sensors for Ca(o)(2+) and probably for other extracellular ions represent versatile regulators of numerous cellular functions and may serve as important therapeutic targets.

  18. A non-invasive method for studying viral DNA delivery to bacteria reveals key requirements for phage SPP1 DNA entry in Bacillus subtilis cells.

    Science.gov (United States)

    Fernandes, Sofia; Labarde, Audrey; Baptista, Catarina; Jakutytè, Lina; Tavares, Paulo; São-José, Carlos

    2016-08-01

    Bacteriophages use most frequently a tail apparatus to create a channel across the entire bacterial cell envelope to transfer the viral genome to the host cell cytoplasm, initiating infection. Characterization of this critical step remains a major challenge due to the difficulty to monitor DNA entry in the bacterium and its requirements. In this work we developed a new method to study phage DNA entry that has the potential to be extended to many tailed phages. Its application to study genome delivery of bacteriophage SPP1 into Bacillus subtilis disclosed a key role of the host cell membrane potential in the DNA entry process. An energized B. subtilis membrane and a millimolar concentration of calcium ions are shown to be major requirements for SPP1 DNA entry following the irreversible binding of phage particles to the receptor YueB. PMID:27179995

  19. DMPD: Calcium signaling in lymphocytes. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available csml) Open .csml file with CIOPlayer Open .csml file with CIOPlayer - ※CIO Playerのご利用上の注意 Open .csml file with CIO Open .csml file with CIO - ※CIOのご利用上の注意 ...

  20. Compartmentalization of the submembrane calcium activity during calcium influx and its significance in transmitter release.

    OpenAIRE

    Simon, S M; Llinás, R R

    1985-01-01

    Quantitative modeling indicates that, in presynaptic terminals, the intracellular calcium concentration profile during inward calcium current is characterized by discrete peaks of calcium immediately adjacent to the calcium channels. This restriction of intracellular calcium concentration suggests a remarkably well specified intracellular architecture such that calcium, as a second messenger, may regulate particular intracellular domains with a great degree of specificity.

  1. Atmospheric Entry Studies for Venus Missions: 45 Sphere-Cone Rigid Aeroshells and Ballistic Entries

    Science.gov (United States)

    Prabhu, Dinesh K.; Spilker, Thomas R.; Allen, Gary A., Jr.; Hwang, Helen H.; Cappuccio, Gelsomina; Moses, Robert W.

    2013-01-01

    The present study considers direct ballistic entries into the atmosphere of Venus using a 45deg sphere-cone rigid aeroshell, a legacy shape that has been used successfully in the past in the Pioneer Venus Multiprobe Mission. For a number of entry mass and heatshield diameter combinations (i.e., various ballistic coefficients) and entry velocities, the trajectory space in terms of entry flight path angles between skip out and -30deg is explored with a 3DoF trajectory code, TRAJ. From these trajectories, the viable entry flight path angle space is determined through the use of mechanical and thermal performance limits on the thermal protection material and science payload; the thermal protection material of choice is entry-grade carbon phenolic, for which a material thermal response model is available. For mechanical performance, a 200 g limit is placed on the peak deceleration load experienced by the science instruments, and 10 bar is assumed as the pressure limit for entry-grade carbon-phenolic material. For thermal performance, inflection points in the total heat load distribution are used as cut off criteria. Analysis of the results shows the existence of a range of critical ballistic coefficients beyond which the steepest possible entries are determined by the pressure limit of the material rather than the deceleration load limit.

  2. Vitamin D, Calcium, and Bone Health

    Science.gov (United States)

    ... Balance › Vitamin D, Calcium, and Bone Health Vitamin D, Calcium, and Bone Health March 2012 Download PDFs ... helps keep your bones strong. Why are vitamin D and calcium important to bone health? Vitamin D ...

  3. Calcium, vitamin D, and your bones

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/patientinstructions/000490.htm Calcium, vitamin D, and your bones To use the sharing ... and maintain strong bones. How Much Calcium and Vitamin D Do I Need? Amounts of calcium are ...

  4. Autonomous gliding entry guidance with geographic constraints

    Institute of Scientific and Technical Information of China (English)

    Guo Jie; Wu Xuzhong; Tang Shengjing

    2015-01-01

    This paper presents a novel three-dimensional autonomous entry guidance for relatively high lift-to-drag ratio vehicles satisfying geographic constraints and other path constraints. The guidance is composed of onboard trajectory planning and robust trajectory tracking. For trajectory planning, a longitudinal sub-planner is introduced to generate a feasible drag-versus-energy profile by using the interpolation between upper boundary and lower boundary of entry corridor to get the desired trajectory length. The associated magnitude of the bank angle can be specified by drag profile, while the sign of bank angle is determined by lateral sub-planner. Two-reverse mode is utilized to satisfy waypoint constraints and dynamic heading error corridor is utilized to satisfy no-fly zone constraints. The longitudinal and lateral sub-planners are iteratively employed until all of the path constraints are satisfied. For trajectory tracking, a novel tracking law based on the active disturbance rejection control is introduced. Finally, adaptability tests and Monte Carlo simulations of the entry guidance approach are performed. Results show that the proposed entry guidance approach can adapt to different entry missions and is able to make the vehicle reach the prescribed target point precisely in spite of geographic constraints.

  5. Calcium transport in turtle bladder

    International Nuclear Information System (INIS)

    Unidirectional 45Ca fluxes were measured in the turtle bladder under open-circuit and short-circuit conditions. In the open-circuited state net calcium flux (JnetCa) was secretory (serosa to mucosa). Ouabain reversed JnetCa to an absorptive flux. Amiloride reduced both fluxes such that JnetCa was not significantly different from zero. Removal of mucosal sodium caused net calcium absorption; removal of serosal sodium caused calcium secretion. When bladders were short circuited, JnetCa decreased to approximately one-third of control value but remained secretory. When ouabain was added under short-circuit conditions, JnetCa was similar in magnitude and direction to ouabain under open-circuited conditions (i.e., absorptive). Tissue 45Ca content was ≅30-fold lower when the isotope was placed in the mucosal bath, suggesting that the apical membrane is the resistance barrier to calcium transport. The results obtained in this study are best explained by postulating a Ca2+-ATPase on the serosa of the turtle bladder epithelium and a sodium-calcium antiporter on the mucosa. In this model, the energy for calcium movement would be supplied, in large part, by the Na+-K+-ATPase. By increasing cell sodium, ouabain would decrease the activity of the mucosal sodium-calcium exchanger (or reverse it), uncovering active calcium transport across the serosa

  6. An Improved Calcium Flame Test.

    Science.gov (United States)

    Pearson, Robert S.

    1985-01-01

    Indicates that the true red color of calcium can be obtained (using the procedure described by Sorm and Logowski) if the calcium ion solution is mixed with an equal volume of saturated ammonium bromide solution. Suggestions for flame tests of other elements are also noted. (JN)

  7. Optimal R&D investment strategies with quantity competition under the threat of superior entry

    OpenAIRE

    Lukach, R.; Kort, P.M.; Plasmans, J.E.J.

    2005-01-01

    This paper studies R&D investment decisions of a firm facing the threat of new technology entry and subject to technical uncertainty. We distinguish four scenarios: inevitable entry, entry deterrence, entry blockade, and non-credible entry threat. The entry threat stimulates the incumbent to innovate in case entry prevention is possible, but discourages R&D if entry is inevitable. In the case of entry deterrence the incumbent successfully prevents entry by innovating. Greater technical uncert...

  8. Two Dimensional Finite Element Model to Study Calcium Distribution in Oocytes

    Science.gov (United States)

    Naik, Parvaiz Ahmad; Pardasani, Kamal Raj

    2015-06-01

    Cytosolic free calcium concentration is a key regulatory factor and perhaps the most widely used means of controlling cellular function. Calcium can enter cells through different pathways which are activated by specific stimuli including membrane depolarization, chemical signals and calcium depletion of intracellular stores. One of the important components of oocyte maturation is differentiation of the Ca2+ signaling machinery which is essential for egg activation after fertilization. Eggs acquire the ability to produce the fertilization-specific calcium signal during oocyte maturation. The calcium concentration patterns required during different stages of oocyte maturation are still not completely known. Also the mechanisms involved in calcium dynamics in oocyte cell are still not well understood. In view of above a two dimensional FEM model has been proposed to study calcium distribution in an oocyte cell. The parameters such as buffers, ryanodine receptor, SERCA pump and voltage gated calcium channel are incorporated in the model. Based on the biophysical conditions the initial and boundary conditions have been framed. The model is transformed into variational form and Ritz finite element method has been employed to obtain the solution. A program has been developed in MATLAB 7.10 for the entire problem and executed to obtain numerical results. The numerical results have been used to study the effect of buffers, RyR, SERCA pump and VGCC on calcium distribution in an oocyte cell.

  9. Respiratory metabolism and calorie restriction relieve persistent endoplasmic reticulum stress induced by calcium shortage in yeast

    Science.gov (United States)

    Busti, Stefano; Mapelli, Valeria; Tripodi, Farida; Sanvito, Rossella; Magni, Fulvio; Coccetti, Paola; Rocchetti, Marcella; Nielsen, Jens; Alberghina, Lilia; Vanoni, Marco

    2016-01-01

    Calcium homeostasis is crucial to eukaryotic cell survival. By acting as an enzyme cofactor and a second messenger in several signal transduction pathways, the calcium ion controls many essential biological processes. Inside the endoplasmic reticulum (ER) calcium concentration is carefully regulated to safeguard the correct folding and processing of secretory proteins. By using the model organism Saccharomyces cerevisiae we show that calcium shortage leads to a slowdown of cell growth and metabolism. Accumulation of unfolded proteins within the calcium-depleted lumen of the endoplasmic reticulum (ER stress) triggers the unfolded protein response (UPR) and generates a state of oxidative stress that decreases cell viability. These effects are severe during growth on rapidly fermentable carbon sources and can be mitigated by decreasing the protein synthesis rate or by inducing cellular respiration. Calcium homeostasis, protein biosynthesis and the unfolded protein response are tightly intertwined and the consequences of facing calcium starvation are determined by whether cellular energy production is balanced with demands for anabolic functions. Our findings confirm that the connections linking disturbance of ER calcium equilibrium to ER stress and UPR signaling are evolutionary conserved and highlight the crucial role of metabolism in modulating the effects induced by calcium shortage. PMID:27305947

  10. CALCIUM ENHANCES ANTIINFLAMMATORY ACTIVITY OF ASPIRIN

    OpenAIRE

    Choksi Krishna; Shenoy Ashoka M; A. R. Shabharaya; Lala Minaxi

    2011-01-01

    The objective of present study is to evaluate the effects of calcium carbonate and calcium gluconate on acute and subacute inflammation and to study their possible interactions with Aspirin. Calcium carbonate (10 mg/kg) and calcium gluconate (5 mg/kg) were administered individually and also co-administered along with sub therapeutic dose Aspirin (50mg/kg) to study their interaction. The inflammation was induced by carrageenan or a foreign body. Both calcium carbonate and calcium gluconate cou...

  11. Multimodal encoding in a simplified model of intracellular calcium signaling

    OpenAIRE

    De Pitta`, Maurizio; Volman, Vladislav; Levine, Herbert; Ben-Jacob, Eshel

    2009-01-01

    Many cells use calcium signalling to carry information from the extracellular side of the plasma membrane to targets in their interior. Since virtually all cells employ a network of biochemical reactions for Ca2+ signalling, much effort has been devoted to understand the functional role of Ca2+ responses and to decipher how their complex dynamics is regulated by the biochemical network of Ca2+-related signal transduction pathways. Experimental observations show that Ca2+ signals in response t...

  12. Remodeling of Calcium Handling in Human Heart Failure

    OpenAIRE

    Lou, Qing; Janardhan, Ajit; Efimov, Igor R.

    2012-01-01

    Heart failure (HF) is an increasing public health problem accelerated by a rapidly aging global population. Despite considerable progress in managing the disease, the development of new therapies for effective treatment of HF remains a challenge. To identify targets for early diagnosis and therapeutic intervention, it is essential to understand the molecular and cellular basis of calcium handling and the signaling pathways governing the functional remodeling associated with HF in humans. Calc...

  13. Biased agonism of the calcium-sensing receptor

    DEFF Research Database (Denmark)

    Thomsen, Alex Rojas Bie; Hvidtfeldt, Maja; Bräuner-Osborne, Hans

    2012-01-01

    calcium-sensing receptor (CaSR), by looking at 12 well-known orthosteric CaSR agonists in 3 different CaSR signaling pathways: G(q/11) protein, G(i/o) protein, and extracellular signal-regulated kinases 1 and 2 (ERK1/2). Here we show that apart from G(q/11) and G(i/o) signaling, ERK1/2 is activated...

  14. Calcium entry induces mitochondrial oxidant stress in vagal neurons at risk in Parkinson’s disease

    OpenAIRE

    Goldberg, Joshua A.; Guzman, Jaime N.; Estep, Chad M.; Ilijic, Ema; Kondapalli, Jyothisri; Sanchez-Padilla, Javier; Surmeier, D. James

    2012-01-01

    Mitochondrial oxidant stress is widely viewed as critical to pathogenesis in Parkinson’s disease. But the origins of this stress are poorly defined. One possibility is that it arises from the metabolic demands associated with regenerative activity. To test this hypothesis, neurons in the dorsal motor nucleus of the vagus (DMV), a population cholinergic neurons that shows signs of pathology in the early stages of Parkinson’s disease, were characterized in mouse brain slices. DMV neurons were s...

  15. Molecular pathways

    DEFF Research Database (Denmark)

    Cox, Thomas R; Erler, Janine Terra

    2014-01-01

    45% of deaths in the developed world are linked to fibrotic disease. Fibrosis and cancer are known to be inextricably linked; however, we are only just beginning to understand the common and overlapping molecular pathways between the two. Here, we discuss what is known about the intersection of...... fibrosis and cancer, with a focus on cancer metastasis, and highlight some of the exciting new potential clinical targets that are emerging from analysis of the molecular pathways associated with these two devastating diseases. Clin Cancer Res; 20(14); 3637-43. ©2014 AACR....

  16. Complex actions of ionomycin in cultured cerebellar astrocytes affecting both calcium-induced calcium release and store-operated calcium entry

    DEFF Research Database (Denmark)

    Müller, Margit S; Obel, Linea Lykke Frimodt; Waagepetersen, Helle S;

    2013-01-01

    The polyether antibiotic ionomycin is a common research tool employed to raise cytosolic Ca(2+) in almost any cell type. Although initially thought to directly cause physicochemical translocation of extracellular Ca(2+) into the cytosol, a number of studies have demonstrated that the mechanism of...

  17. Limestone reaction in calcium aluminate cement–calcium sulfate systems

    International Nuclear Information System (INIS)

    This paper reports a study of ternary blends composed of calcium aluminate cement, calcium sulfate hemihydrate and limestone. Compressive strength tests and hydration kinetics were studied as a function of limestone and calcium sulfate content. The phase evolution and the total porosity were followed and compared to thermodynamic simulation to understand the reactions involved and the effect of limestone on these binders. The reaction of limestone leads to the formation of hemicarboaluminate and monocarboaluminate. Increasing the ratio between sulfate and aluminate decreases the extent of limestone reaction

  18. Role of calcium in the constriction of isolated cerebral arteries

    International Nuclear Information System (INIS)

    Calcium entry blockers (CEB) have been used in the experimental treatment or prevention of many cerebrovascular disorders including stroke, post-ischemic hypoperfusion after cardiac arrest, cerebral vasospasm after subarachnoid hemorrhage, and migraine headache. However, the mechanism of action of these drugs on the cerebral circulation is poorly understood. This study examined the effects of calcium antagonists, Ca2+-deficient solutions, and vasocostrictors on cerebrovascular tone and 45Ca fluxes, to determine the role of calcium in cerebral arterial constriction. A Scatchard plot of 45Ca binding to BMCA showed that Ca2+ was bound at either low or high affinity binding sties. The four vasoconstrictors (potassium, serotonin, PGF/sub 2 α/, or SQ-26,655) each increased low affinity 45Ca uptake into BMCA. The results demonstrate that: (1) Potassium and serotonin constrict BMCA mainly by promoting Ca2+ influx through CEB-sensitive channels; (2) PGF/sub 2 α/ and SQ-26,655 constrict BMCA in part by promoting Ca2+ influx through CEB-sensitive channels, and in part by releasing Ca2+ from depletable internal stores; (3) The major action of CEB on BMCA is to block vasoconstrictor-induced Ca2+ uptake through both potential-operated (K+-stimulated) and receptor-operated channels

  19. Ca2+ signals induced from calcium stores in pancreatic islet β cells

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    In single rat pancreatic β cells,using fura-2 microfluorometry to measure [Ca2+]i response upon different stimuli,the ways of calcium regulation have been studied.When the extracellular calcium concentration was 2.5 mmol/L,either 60 mmol/L KCl,20 mmol/L D-glucose or 0.1 mmol/L tolbutamide induced increase in [Ca2+]i.Such increase in [Ca2+]i was absent when the same stimuli were applied under zero extracellular calcium.These results indicate that the increase of [Ca2+]i is induced by the activation of voltage-dependent calcium channels in β cells.The manifold forms of [Ca2+]i change induced by glucose imply that the effects of glucose are complex.5 mmol/L caffeine or 5 mmol/L MCh increase the [Ca2+]i ,which is independent of the external calcium,suggesting that [Ca2+]i can be regulated by Ca2+ release from not only the IP3-sensitive but also the ryanodine sensitive calcium stores in β cells.The latency of Ca responses for IP3 pathway (5 s) is faster than that for ryanodine pathway (30 s).It is concluded that there are multiple calcium stores in rat pancreatic β cells.

  20. Effect of Bcl-2 and caspase-3 on calcium distribution in apoptosis of HL-60 cells

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Apoptosis manifests in two major execution programs downstream of the death signal: the caspase pathway and organelle dysfunction. An important antiapoptosis factor, Bcl-2 protein, contributes in caspase pathway of apoptosis. Calcium, an important intracellular signal element in cells, is also observed to have changes during apoptosis, which maybe affected by Bcl2 protein. We have previously reported that in Harringtonine (HT) induced apoptosis of HL-60 cells, there's a change of intracellular calcium distribution, moving from cytoplast especially Golgi's apparatus to nucleus and accumulating there with the highest concentration. We report here that caspase-3 becomes activated in HT-induced apoptosis of HL-60 cells, which can be inhibited by overexpression of Bcl-2 protein. No sign of apoptosis or intracellular calcium movement from Golgi's apparatus to nucleus in HL-60 cells overexpressing Bcl-2 or treated with Ac-DEVD-CHO, a specific inhibitor of caspase-3. The results indicate that activated caspase-3 can promote the movement of intracellular calcium from Golgi's apparatus to nucleus, and the process is inhibited by Ac-DEVD-CHO (inhibitor of caspas-3), and that Bcl-2 can inhibit the movement and accumulation of intracellular calcium in nucleus through its inhibition on caspase3. Calcium relocalization in apoptosis seems to be irreversible, which is different from the intracellular calcium changes caused by growth factor.

  1. Effect of hydrocortisone on total body calcium in rats. [/sup 47/Ca and /sup 85/Sr tracer techniques

    Energy Technology Data Exchange (ETDEWEB)

    Yasumura, S.; Ellis, K.J.; Cohn, S.H.

    1976-11-01

    Administration of 5 mg. of hydrocortisone acetate to rats every other day for 2 weeks resulted in growth retardation and weight loss as indicated by body weights of experimental animals, which averaged 33 percent lower than those of the controls, and a significant decrease in the length of the tibiae and femurs (p less than 0.01 for treated vs controls). However, despite the smaller size of the treated animals, the values for total body calcium (TBCa) and the calcium in the tibia and femur did not differ significantly from control values. Thus, there was more calcium per unit length of bone, resulting in an increase in the skeletal density of treated rats. This finding was confirmed by x-ray examination of these bones. The net intestinal absorption of calcium (rate of initial entry) calculated from plasma levels following an oral and intravenous dose of /sup 47/Ca and /sup 85/Sr, respectively, was not significantly different in hydrocortisone-treated rats compared to controls. This would indicate that the rate of intestinal absorption of calcium is unimpaired despite the administration of massive doses of corticosteroids. When the animals were placed on a calcium-deficient diet, both TBCa and tibia and femur calcium levels were decreased. Subsequent administration of hydrocortisone did not alter the calcium values. The results of this study are compatible with the hypothesis that hydrocortisone promotes weight loss, retards growth, but inhibits the rate of bone resorption.

  2. RTLS entry ranging analysis. [space shuttle reentry trajectory

    Science.gov (United States)

    Crull, T. J.

    1975-01-01

    Definition of the ranging capability of a mission 3A return-to-launch-site entry is reported. The limits on downrange and crossrange are established at the initiation of RTLS entry so that terminal area energy management interface conditions were achieved satisfactorily. The downrange and crossrange limits were defined for both nominal RTLS entry conditions and a composite set of dispersed RTLS entry conditions. The results indicate a wide range of acceptable downrange and crossrange positions are available at RTLS entry initiation for nominal conditions. This is greatly reduced when dispersions are considered. For dispersed RTLS entry conditions, an 18 nautical mile range of acceptable downranges is available at zero crossrange.

  3. Perceptions regarding strategic and structural entry barriers

    NARCIS (Netherlands)

    Lutz, Clemens H. M.; Kemp, Ron G. M.; Dijkstra, S. Gerhard

    2010-01-01

    This article uses factor analysis to identify the underlying dimensions of strategic and structural entry barriers. We find that, in the perception of firms, both types of barriers are important and that the effectiveness of strategic barriers depends on attributes of the market structure. Based on

  4. Duopoly Dynamics with a Barrier to Entry

    NARCIS (Netherlands)

    Abbring, J.H.; Campbell, Jeffrey R.

    2007-01-01

    This paper considers the effects of raising the cost of entry for a potential competitor on infinite-horizon Markov-perfect duopoly dynamics with ongoing demand uncertainty. All entrants serving the model industry incur sunk costs, and exit avoids future fixed costs. We focus on the unique equilibri

  5. Septins regulate bacterial entry into host cells.

    Directory of Open Access Journals (Sweden)

    Serge Mostowy

    Full Text Available BACKGROUND: Septins are conserved GTPases that form filaments and are required in many organisms for several processes including cytokinesis. We previously identified SEPT9 associated with phagosomes containing latex beads coated with the Listeria surface protein InlB. METHODOLOGY/PRINCIPAL FINDINGS: Here, we investigated septin function during entry of invasive bacteria in non-phagocytic mammalian cells. We found that SEPT9, and its interacting partners SEPT2 and SEPT11, are recruited as collars next to actin at the site of entry of Listeria and Shigella. SEPT2-depletion by siRNA decreased bacterial invasion, suggesting that septins have roles during particle entry. Incubating cells with InlB-coated beads confirmed an essential role for SEPT2. Moreover, SEPT2-depletion impaired InlB-mediated stimulation of Met-dependent signaling as shown by FRET. CONCLUSIONS/SIGNIFICANCE: Together these findings highlight novel roles for SEPT2, and distinguish the roles of septin and actin in bacterial entry.

  6. 32 CFR 763.5 - Entry procedures.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 5 2010-07-01 2010-07-01 false Entry procedures. 763.5 Section 763.5 National Defense Department of Defense (Continued) DEPARTMENT OF THE NAVY ISLANDS UNDER NAVY JURISDICTION RULES... penal codes may be prosecuted by the Federal Government and/or barred from any future access to...

  7. 40 CFR 170.112 - Entry restrictions.

    Science.gov (United States)

    2010-07-01

    .... (2) Entry-restricted areas in greenhouses are specified in column D in table 2 under § 170.110(c)(4... at the appropriate address as set forth in 40 CFR 150.17(a) or (b) and must be accompanied by two...; using an alternative to the hand labor tasks, such as machine cultivation; or substituting a...

  8. Flavivirus cell entry and membrane fusion

    NARCIS (Netherlands)

    Smit, Jolanda M.; Moesker, Bastiaan; Rodenhuis-Zybert, Izabela; Wilschut, Jan

    2011-01-01

    Flaviviruses, such as dengue virus and West Nile virus, are enveloped viruses that infect cells through receptor-mediated endocytosis and fusion from within acidic endosomes. The cell entry process of flaviviruses is mediated by the viral E glycoprotein. This short review will address recent advance

  9. Entry modes of European firms in Vietnam

    Directory of Open Access Journals (Sweden)

    Daniel Simonet

    2012-09-01

    Full Text Available Purpose: The purpose of the paper is to explore the entry modes of EU firms setting up operations in Vietnam. Design/methodology/approach: we use a case study approach on Haymarket, Cadbury, Creative Education, Fairchild, Aventis and Artemisinin and Farming International using interviews from managerial professionals in Vietnam. Findings: Despite the fact that Vietnam has been opening up for more than 20 years, licensing is the preferred entry mode because of the risks involved in venturing with local firms; that preference signals a low level commitment and a high perception of risk and state interference. In line with Vietnam transition to state - rather than private market - capitalism, a foreign company opting for a joint-venture will do so with a state-owned rather than privately-owned company. The choice of a subsidiary can be explained by the lack of trust in partners and institutions, not by improvement in the socio-political environment. Limitations: In determining the entry mode strategy, the paper focuses on the Uppsala school’s “psychic distance” (e.g. cultural distance, lack of trust rather than on firm-specific advantages (Rugman, 1980; 2006. Key-words: international entry mode; emerging markets; subsidiary; joint-venture; India; Vietnam

  10. p53 Prevents Entry into Mitosis with Uncapped Telomeres

    Science.gov (United States)

    Thanasoula, Maria; Escandell, Jose Miguel; Martinez, Paula; Badie, Sophie; Muñoz, Purificacion; Blasco, María A.; Tarsounas, Madalena

    2016-01-01

    Summary Telomeres are protected by capping structures consisting of core protein complexes that bind with sequence specificity to telomeric DNA (reviewed in [1]). In their absence, telomeres trigger a DNA damage response, materialized in accumulation at the telomere of damage response proteins, e.g., phosphorylated histone H2AX (γH2AX), into telomere-dysfunction-induced foci [2, 3]. Telomere uncapping occurs transiently in every cell cycle in G2 [4], following DNA replication, but little is known about how protective structures are reassembled or whether this process is controlled by the cell-cycle surveillance machinery. Here, we report that telomere capping is monitored at the G2/M transition by the p53/p21 damage response pathway. Unlike their wild-type counterparts, human and mouse cells lacking p53 or p21 progress into mitosis prematurely with persisting uncapped telomeres. Furthermore, artificially uncapped telomeres delay mitotic entry in a p53- and p21-dependent manner. Uncapped telomeres that persist in mitotic p53-deficient cells are shorter than average and religate to generate end-to-end fusions. These results suggest that a p53-dependent pathway monitors telomere capping after DNA replication and delays G2/M progression in the presence of unprotected telomeres. This mechanism maintains a cell-cycle stage conducive for capping reactions and prevents progression into stages during which uncapped telomeres are prone to deleterious end fusions. PMID:20226664

  11. PRACTITIONER AND FACULTY PERSPECTIVES ON THE CAREER PREPARATION OF ENTRY-LEVEL PUBLIC ACCOUNTANTS

    Directory of Open Access Journals (Sweden)

    Kathryn Simms

    2012-01-01

    Full Text Available Entry-level public accountants in the U.S. must satisfy a litany of historically unparalleled requirements and demands. This unique set of challenges calls forth new questions about how effectively entry-level accountants are navigating the divide between their conceptual educations and the practical rigors of public practice. To examine these questions, we relied on qualitative analysis predicated on a theoretical framework of constructivism and systems theory. Our study confirmed practitioners’ perceptions about the preparation of entry-level accountants that have been documented for nearly a hundred years: Entry-level accountants’ shortcomings often include written and oral communications skills, interpersonal skills and critical thinking skills. However, what is unique to this study is that we also considered faculty perspectives. Faculty concurred with practitioners’ perspectives on entry-level accountants’ strengths and weaknesses-noting considerable growth in most problem areas over the college years. Practitioners and faculty also largely agreed about the pathway to successful and unsuccessful careers in public accounting. We suggest that continuing the historical perspective of extreme separation between academia and the business world is not particularly beneficial to the career preparation of junior accountants. Rather, we recommend that viewing accounting faculty and practitioners as part of the same continuum is likely to be more advantageous to the preparation of entry-level accountants and to the profession as a whole. We also conclude that differences in faculty and practitioner perspectives serve as checks and balances on the accounting profession-although more collaboration might facilitate greater improvements.

  12. Calcium carbonate and calcium sulfate in Martian meteorite EETA79001

    Science.gov (United States)

    Gooding, J. L.; Wentworth, S. J.

    1987-01-01

    Chips of glassy Lithology C of EETA79001 were studied by scanning electron microscopy and energy dispersive X-ray spectroscopy to determine the mineralogy and petrogenesis of the glass that was shown by others to contain trapped Mars-like gases. Calcium carbonite was identified as massive to acicular crystals for which Ca, C, and O were the major elements. Calcium sulfate was identified as prismatic-acicular crystals with Ca and S as the major elements.

  13. Estimation of presynaptic calcium currents and endogenous calcium buffers at the frog neuromuscular junction with two different calcium fluorescent dyes

    OpenAIRE

    Samigullin, Dmitry; Fatikhov, Nijaz; Khaziev, Eduard; Skorinkin, Andrey; Nikolsky, Eugeny; Bukharaeva, Ellya

    2015-01-01

    At the frog neuromuscular junction, under physiological conditions, the direct measurement of calcium currents and of the concentration of intracellular calcium buffers—which determine the kinetics of calcium concentration and neurotransmitter release from the nerve terminal—has hitherto been technically impossible. With the aim of quantifying both Ca2+ currents and the intracellular calcium buffers, we measured fluorescence signals from nerve terminals loaded with the low-affinity calcium dy...

  14. Market Entry Strategies : Case: McDonald's entry on the Russian market

    OpenAIRE

    Karataev, Oleg

    2015-01-01

    The thesis considers the entry strategy and development of the company McDonald's into international markets. The theoretical aspects of the entry strategy of the company into the international markets. Analyzes the key features of the development of McDonald's in Russia. Investigated the prospects of the company in international markets. In theoretic part there was regarded some important aspects of international strategic management, such as: strategic alternatives, elements and levels o...

  15. Variability of calcium absorption

    International Nuclear Information System (INIS)

    Variability in calcium absorption was estimated in three groups of normal subjects in whom Ca absorption was measured by standard isotopic-tracer methods at interstudy intervals ranging from 1 to 4 mo. Fifty absorption tests were performed in 22 subjects. Each was done in the morning after an overnight fast with an identical standard breakfast containing a Ca load of approximately 250 mg. Individual fractional absorption values were normalized to permit pooling of the data. The coefficient of variation (CVs) for absorption for the three groups ranged from 10.57 to 12.79% with the size of the CV increasing with interstudy duration. One other published study presenting replicate absorption values was analyzed in a similar fashion and was found to have a CV of absorption of 9.78%. From these data we estimate that when the standard double-isotope method is used to measure Ca absorption there is approximately 10% variability around any given absorption value within an individual human subject and that roughly two-thirds of this represents real biological variability in absorption

  16. Endolymphatic calcium supply for fish otolith growth takes place via the proximal portion of the otocyst.

    Science.gov (United States)

    Ibsch, M; Anken, R; Beier, M; Rahmann, H

    2004-09-01

    The presence of calcium within the utricle of larval cichlid fish Oreochromis mossambicus was analysed by means of energy-filtering transmission electron microscopy. Electron-spectroscopic imaging and electron energy loss spectra revealed discrete calcium precipitations that were more numerous in the proximal endolymph than in the distal endolymph, clearly indicating a decreasing proximo-distal gradient. This decreasing proximo-distal gradient was also present within the proximal endolymph between the sensory epithelium and the otolith. Further calcium particles covered the peripheral proteinaceous layer of the otolith. They were especially pronounced at the proximal surface of the otolith indicating that otolithic calcium incorporation takes place here. Other calcium precipitates accumulated at the macular junctions clearly supporting an earlier assumption according to which the endolymph is supplied with calcium via a paracellular pathway. The present results clearly show that the apical region of the macular epithelium is involved in the release of calcium and that the calcium supply of the otoliths takes place via the proximal endolymph. PMID:15300493

  17. Swimming behaviour and calcium incorporation into inner ear otoliths of fish after vestibular nerve transection

    Science.gov (United States)

    Edelmann, E.; Anken, R. H.; Rahmann, H.

    2004-01-01

    Previous investigations on neonate swordtail fish (Xiphophorus helleri) revealed that otolithic calcium incorporation (visualized using the calcium tracer alizarin complexone) and thus otolith growth had ceased after nerve transection, supporting a hypothesis according to which the gravity-dependent otolith growth is regulated neuronally. Subsequent investigations on larval cichlid fish (Oreochromis mossambicus) yielded contrasting results, repeatedly depending on the particular batch of cichlids investigated. Like most neonate swordtails, Type I cichlids revealed a stop of calcium incorporation after unilateral vestibular nerve transection. Their behaviour after transection was normal, and the otolithic calcium incorporation in controls of the same batch was symmetric. In Type II cichlids, however, vestibular nerve transection had no effect on otolithic calcium incorporation. They behaved kinetotically after transection (this kind of kinetosis was qualitatively similar to the swimming behaviour exhibited by larval cichlids during microgravity in the course of parabolic aircraft flights). The otolithic calcium incorporation in control animals was asymmetric. These results show that the effects of vestibular nerve transection as well as the efficacy of the mechanism, which regulates otolith growth/otolithic calcium incorporation, are - depending on the particular batch of animals - genetically predispositioned. In conclusion, the regulation of otolithic calcium incorporation is guided neuronally, in part via the vestibular nerve and, in part, via a further pathway, which remains to be addressed in the course of future investigations.

  18. Calcium regulation of EGF-induced ERK5 activation: role of Lad1-MEKK2 interaction.

    Directory of Open Access Journals (Sweden)

    Zhong Yao

    Full Text Available The ERK5 cascade is a MAPK pathway that transmits both mitogenic and stress signals, yet its mechanism of activation is not fully understood. Using intracellular calcium modifiers, we found that ERK5 activation by EGF is inhibited both by the depletion and elevation of intracellular calcium levels. This calcium effect was found to occur upstream of MEKK2, which is the MAP3K of the ERK5 cascade. Co-immunoprecipitation revealed that EGF increases MEKK2 binding to the adaptor protein Lad1, and this interaction was reduced by the intracellular calcium modifiers, indicating that a proper calcium concentration is required for the interactions and transmission of EGF signals to ERK5. In vitro binding assays revealed that the proper calcium concentration is required for a direct binding of MEKK2 to Lad1. The binding of these proteins is not affected by c-Src-mediated phosphorylation on Lad1, but slightly affects the Tyr phosphorylation of MEKK2, suggesting that the interaction with Lad1 is necessary for full Tyr phosphorylation of MEKK2. In addition, we found that changes in calcium levels affect the EGF-induced nuclear translocation of MEKK2 and thereby its effect on the nuclear ERK5 activity. Taken together, these findings suggest that calcium is required for EGF-induced ERK5 activation, and this effect is probably mediated by securing proper interaction of MEKK2 with the upstream adaptor protein Lad1.

  19. Dengue-3 Virus Entry into Vero Cells: Role of Clathrin-Mediated Endocytosis in the Outcome of Infection

    Science.gov (United States)

    Piccini, Luana E.; Castilla, Viviana; Damonte, Elsa B.

    2015-01-01

    The endocytic uptake and intracellular trafficking for penetration of DENV-3 strain H-87 into Vero cells was analyzed by using several biochemical inhibitors and dominant negative mutants of cellular proteins. The results presented show that the infective entry of DENV-3 into Vero cells occurs through a non-classical endocytosis pathway dependent on low pH and dynamin, but non-mediated by clathrin. After uptake, DENV-3 transits through early endosomes to reach Rab 7-regulated late endosomes, and according with the half-time for ammonium chloride resistance viral nucleocapsid is released into the cytosol approximately at 12 min post-infection. Furthermore, the influence of the clathrin pathway in DENV-3 infective entry in other mammalian cell lines of human origin, such as A549, HepG2 and U937 cells, was evaluated demonstrating that variable entry pathways are employed depending on the host cell. Results show for the first time the simultaneous coexistence of infective and non -infective routes for DENV entry into the host cell, depending on the usage of clathrin-mediated endocytosis. PMID:26469784

  20. Dengue-3 Virus Entry into Vero Cells: Role of Clathrin-Mediated Endocytosis in the Outcome of Infection.

    Science.gov (United States)

    Piccini, Luana E; Castilla, Viviana; Damonte, Elsa B

    2015-01-01

    The endocytic uptake and intracellular trafficking for penetration of DENV-3 strain H-87 into Vero cells was analyzed by using several biochemical inhibitors and dominant negative mutants of cellular proteins. The results presented show that the infective entry of DENV-3 into Vero cells occurs through a non-classical endocytosis pathway dependent on low pH and dynamin, but non-mediated by clathrin. After uptake, DENV-3 transits through early endosomes to reach Rab 7-regulated late endosomes, and according with the half-time for ammonium chloride resistance viral nucleocapsid is released into the cytosol approximately at 12 min post-infection. Furthermore, the influence of the clathrin pathway in DENV-3 infective entry in other mammalian cell lines of human origin, such as A549, HepG2 and U937 cells, was evaluated demonstrating that variable entry pathways are employed depending on the host cell. Results show for the first time the simultaneous coexistence of infective and non -infective routes for DENV entry into the host cell, depending on the usage of clathrin-mediated endocytosis. PMID:26469784

  1. Dengue-3 Virus Entry into Vero Cells: Role of Clathrin-Mediated Endocytosis in the Outcome of Infection.

    Directory of Open Access Journals (Sweden)

    Luana E Piccini

    Full Text Available The endocytic uptake and intracellular trafficking for penetration of DENV-3 strain H-87 into Vero cells was analyzed by using several biochemical inhibitors and dominant negative mutants of cellular proteins. The results presented show that the infective entry of DENV-3 into Vero cells occurs through a non-classical endocytosis pathway dependent on low pH and dynamin, but non-mediated by clathrin. After uptake, DENV-3 transits through early endosomes to reach Rab 7-regulated late endosomes, and according with the half-time for ammonium chloride resistance viral nucleocapsid is released into the cytosol approximately at 12 min post-infection. Furthermore, the influence of the clathrin pathway in DENV-3 infective entry in other mammalian cell lines of human origin, such as A549, HepG2 and U937 cells, was evaluated demonstrating that variable entry pathways are employed depending on the host cell. Results show for the first time the simultaneous coexistence of infective and non -infective routes for DENV entry into the host cell, depending on the usage of clathrin-mediated endocytosis.

  2. Entry Location and Entry Timing (ELET Decision Model for International Construction Firms

    Directory of Open Access Journals (Sweden)

    Che Maznah Mat Isa

    2014-09-01

    Full Text Available This paper proposes a model for entry location (EL and entry timing (ET decisions to guide construction firms in accessing targeted international markets.  Neglecting to properly choose the right combination of the entry location and entry timing (ELET decisions can lead to poor performance of the firms’ international ventures.  The sampling frame was from the Malaysian construction firms that have undertaken and completed projects abroad.  Survey questionnaires sent to 115 firms registered with Construction Industry Development Board (CIDB Malaysia, operating in more than 50 countries, achieved a 39.1 per cent response rate. Based on a comprehensive statistical analysis of survey data it was found that the mutually inclusive significant factors that influenced the firms’ ELET decisions were: the firm’s ability to assess market signals and opportunities, international experience, financial capacity, competencies and capabilities (project management, specialist expertise and technology, resources (level of knowledge based on research and development, experience in similar works, financial support from the home country banks, technical complexities of projects and availability of funds for projects.  Hence, the present research builds on and extends the literature on the ELET decisions in a more integrated way. Keywords: Entry location, entry timing, resource-based view, international markets, Malaysian construction firms.

  3. Design and Simulation Tools for Planetary Atmospheric Entry Vehicles Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Atmospheric entry is one of the most critical phases of flight during planetary exploration missions. During the design of an entry vehicle, experimental and...

  4. Adaptive Deployable Entry and Placement Technology (ADEPT) Project

    Data.gov (United States)

    National Aeronautics and Space Administration — The ADEPT Project is developing a mechanically deployable low-ballistic coefficient aeroshell entry system to perform entry descent landing (EDL) functions for...

  5. Calcium-sensitive immunoaffinity chromatography

    DEFF Research Database (Denmark)

    Henriksen, Maiken L; Lindhardt Madsen, Kirstine; Skjoedt, Karsten;

    2014-01-01

    homogeneity may be impossible due to contamination with abundant antigens. In this study, we purified the scarce, complement-associated plasma protein complex, collectin LK (CL-LK, complex of collectin liver 1 and kidney 1), by immunoaffinity chromatography using a calcium-sensitive anti-collectin-kidney-1 m......Ab. This antibody was characterized by binding to CL-LK at hypo- and physiological calcium concentrations and dissociated from CK-LK at hyperphysiological concentrations of calcium. We purified CL-LK from plasma to a purity of 41% and a yield of 38%, resulting in a purification factor of more than 88......,000 in a single step. To evaluate the efficiency of this new purification scheme, we purified CL-LK using the same calcium-sensitive mAb in combination with acidic elution buffer and by using calcium-dependent anti-CL-K1 mAbs in combination with EDTA elution buffer. We found that calcium...

  6. Role of Dickeya dadantii 3937 chemoreceptors in the entry to Arabidopsis leaves through wounds.

    Science.gov (United States)

    Río-Álvarez, Isabel; Muñoz-Gómez, Cristina; Navas-Vásquez, Mariela; Martínez-García, Pedro M; Antúnez-Lamas, María; Rodríguez-Palenzuela, Pablo; López-Solanilla, Emilia

    2015-09-01

    Chemotaxis enables bacteria to move towards an optimal environment in response to chemical signals. In the case of plant-pathogenic bacteria, chemotaxis allows pathogens to explore the plant surface for potential entry sites with the ultimate aim to prosper inside plant tissues and to cause disease. Chemoreceptors, which constitute the sensory core of the chemotaxis system, are usually transmembrane proteins which change their conformation when sensing chemicals in the periplasm and transduce the signal through a kinase pathway to the flagellar motor. In the particular case of the soft-rot pathogen Dickeya dadantii 3937, jasmonic acid released in a plant wound has been found to be a strong chemoattractant which drives pathogen entry into the plant apoplast. In order to identify candidate chemoreceptors sensing wound-derived plant compounds, we carried out a bioinformatics search of candidate chemoreceptors in the genome of Dickeya dadantii 3937. The study of the chemotactic response to several compounds and the analysis of the entry process to Arabidopsis leaves of 10 selected mutants in chemoreceptors allowed us to determine the implications of at least two of them (ABF-0020167 and ABF-0046680) in the chemotaxis-driven entry process through plant wounds. Our data suggest that ABF-0020167 and ABF-0046680 may be candidate receptors of jasmonic acid and xylose, respectively. PMID:25487519

  7. Strategic Advantage and the Optimal Exercise of Entry Options

    OpenAIRE

    Perotti, Enrico C; Rossetto, Silvia

    2001-01-01

    We investigate the timing and the valuation of strategic investment aimed at enhancing entry opportunities in related market segments. As demand is uncertain, entry options should be exercised at the optimal time, trading off the market share gain against the option to wait until more information is revealed, while anticipating competitors' entry behaviour. When the strategic investment grants a strong competitive advantage, the innovator can optimally choose the timing of entry; in case of w...

  8. Model-based guidance and control for atmospheric guided entry

    OpenAIRE

    Canuto, Enrico; Ospina, Jose Alejandro

    2012-01-01

    This paper presents a solution of the translational control for a biconic atmospheric entry capsule using the bank angle as a command. The control algorithm is separated into path planning and reference-path tracking. The path-planning algorithm computes the entry trajectory from the navigated state at the Entry Interface Point until the desired Parachute Deployment Point. The algorithm aims to recover the landing site uncertainty caused by Entry Interface Point dispersions. Atmospheric and a...

  9. RITD - Re-entry: Inflatable Technology Development in Russian Collaboration

    Science.gov (United States)

    Heilimo, J.; Harri, A.-M.; Aleksashkin, S.; Koryanov, V.; Arruego, I.; Schmidt, W.; Haukka, H.; Finchenko, V.; Martynov, M.; Ostresko, B.; Ponomarenko, A.; Kazakovtsev, V.; Martin, S.; Siili, T.

    2014-04-01

    A new generation of inflatable Entry, Descent and Landing System (EDLS) for Mars has been developed. It is used in both the initial atmospheric entry and atmospheric descent before the semi-hard impact of the penetrator into Martian surface. The EDLS applicability to Earth's atmosphere is studied by the EU/RITD [1] project. Project focuses on the analysis and tests of the transonic behaviour of this compact and light weight payload entry system at the Earth re-entry.

  10. Multi entry framework for financial and risk reporting

    OpenAIRE

    Staszkiewicz, Piotr W.

    2011-01-01

    Author challenges one of the oldest accounting double bookkeeping rules, used since 1494, and proposes instead application of the quadruple accounting entry. He presents the concept of the multiply accounting entry for the risk financial statements and risk management. The development gap concept is described and introduces a simplified entry and reporting example. Model is illustrated with a number of financial-risk statements and attributes including the journal entries. The potential co...

  11. Free Entry and Social Inefficiency in Radio Broadcasting

    OpenAIRE

    Steven Berry; Joel Waldfogel

    1996-01-01

    In theory, free entry can lead to social inefficiency. When new products are substitutes for existing products, the business stolen from incumbents places a wedge between private and social benefits of entry. The business stealing effect can be offset if entry reduces prices or increases available product variety. Our study of the radio industry provides one of the first empirical attempts to quantify the inefficiency associated with free entry. Using data on advertising prices, number of sta...

  12. Analyzing Modes of Foreign Entry. Greenfield Investment versus Acquisition

    OpenAIRE

    Müller, Thomas

    2001-01-01

    This paper studies the entry decision of a multinational enterprise into a foreign market. Two alternative entry modes for a foreign direct investment are considered: Greenfield investment versus acquisition. In contrast to existing approaches, the acquisition price and the profits under both entry modes are endogenously determined. Interestingly, we find that the optimal entry mode decision is a ected by the competition intensity in the market in a non-monotonic way. When markets are very mu...

  13. Get Taiwanized! : Swedish Firms' Change of Entry Mode

    OpenAIRE

    Nilsson, Karin; Olofsson, Elisabet; Sennevik, Marie

    2005-01-01

    Expanding to foreign markets is increasingly popular for companies. The company has to decide which organisational structure, entry mode, to use in the new market. Factors affecting the change from one entry mode to another have obtained little attention. This thesis concerns Swedish companies’ changes of entry mode in Taiwan. The purpose is to investigate which factors that serve as triggers respectively barriers for the change of entry modes, to be able to examine which theories that can be...

  14. SMEs entry mode decision making process: Rational or cybernetic?

    OpenAIRE

    Quan, Rose

    2012-01-01

    Entry mode choice is a critical decision when a firm expends its business to foreign markets. By applying rational and cybernetic strategies to international strategic decision-making process, this paper investigates how small and medium sized firms (SMEs) decision makers decide their entry mode choices. By focusing on the entry decision making process, this research distinguishes the prior entry mode studies that emphasize the relationship between influencing factors and their impacts on ent...

  15. Collusion and downstream entry in a vertically integrated industry

    OpenAIRE

    Éric Avenel; Stéphane Caprice

    2012-01-01

    We analyse the impact of an entry threat at the downstream level on the ability of a pair of vertically integrated incumbents to collude. We present an original model of horizontal product differentiation on the final market and characterize the structures of this market for which an entry threat facilitates collusion between incumbents. While the entry threat leaves collusion and deviation profits unchanged, it lowers profits in punishment periods. Consequently, an entry threat discourages d...

  16. Secretory pathway Ca2+/Mn2+-ATPase isoform 2 and lactation: specific localization of plasmalemmal and secretory pathway Ca2+ pump isoforms in the mammary gland

    Energy Technology Data Exchange (ETDEWEB)

    Faddy, Helen M.; Smart, Chanel E.; Xu, Ren; Lee, Genee Y.; Kenny, Paraic A.; Feng, Mingye; Rao, Rajini; Brown, Melissa A.; Bissell, Mina J.; Roberts-Thomson, Sarah J.; Monteith, Gregory R.

    2008-04-09

    The supply of calcium to the developing neonate via milk is an important physiological process. Until recently the mechanism for the enrichment of milk with calcium was thought to be almost entirely mediated via the secretory pathway. However, recent studies suggest that a specific isoform of the plasma membrane calcium ATPase, PMCA2, is the primary mechanism for calcium transport into milk, highlighting a major role for apical calcium transport. We compared the expression of the recently identified secretory calcium ATPase, SPCA2, and SPCA1, in the mouse mammary gland during different stages of development. SPCA2 levels increased over 35 fold during lactation, while SPCA1 increased only a modest two fold. The potential importance of SPCA2 in lactation was also highlighted by its localization to luminal secretory cells of the mammary gland during lactation, while SPCA1 was expressed throughout the cells of the mammary gland. We also observed major differences in the localization of PMCA2 and PMCA1 during lactation. Using the SCp2 mouse mammary epithelial cell 3D culture model, differences in the sub-cellular distribution of PMCA2 and PMCA1 were clear. These studies highlight the likely specific roles of PMCA2 and SPCA2 in lactation, and link the recently characterized SPCA2 calcium pump to the supply of calcium into milk and the regulation of Golgi resident enzymes important in lactation. They also indicate that calcium transport into milk is a complex interplay between apical and secretory pathways.

  17. An activation-repolarization time metric to predict localized regions of high susceptibility to re-entry

    Science.gov (United States)

    Child, Nicholas; Bishop, Martin J.; Hanson, Ben; Coronel, Ruben; Opthof, Tobias; Bourkens, Bastiaan; Walton, Richard; Efimov, Igor; Bostock, Julian; Hill, Yolanda; Rinaldi, Christopher A; Razavi, Reza; Gill, Jaswinder; Taggart, Peter

    2015-01-01

    Background Initiation of re-entrant ventricular tachycardia (VT) involves complex interactions between activation and repolarization wavefronts. Recent experimental work has identified the time interval between S2 repolarization proximal to a line of functional block and the activation at the adjacent distal side, as a critical determinant of re-entry. Objective We hypothesized: (1) an algorithm could be developed which would generate a spatial map of this interval (designated the “re-entry vulnerability index”-RVI); (2) that this would accurately identify a pathway of re-entry as well as rotor formation in animal experiments and in a computational model; and, (3) that it would be possible to generate an RVI map in humans during routine clinical procedures and co-register with anatomical and electrophysiological features. Methods and Results An algorithm was developed which sampled all points on a multielectrode grid and calculated RVI between all pairs of electrodes within a given radius. The algorithm successfully identified the spatial region with increased susceptibility to re-entry in an established Langendorff pig heart model and the site of re-entry and rotor formation in an optically mapped sheep heart model and corresponding computational simulations. The feasibility of RVI mapping was evaluated during a clinical procedure by co-registering with the anatomy and physiology in a patient undergoing a VT ablation. Conclusions We developed an algorithm to calculate a re-entry vulnerability index from intervals between local repolarization and activation times at all adjacent points over a multielectrode grid. The algorithm accurately identified the region of re-entry in two animal models of functional re-entry. The possibility of clinical application was demonstrated in a patient with VT. PMID:25863160

  18. The Double-Entry Journal in Literature Classes.

    Science.gov (United States)

    Nugent, Harold; Nugent, Susan

    The double-entry journal requires students to write affective response statements to literature readings and to compare such entries with those of classmates. Use of the double-entry journal is intended to activate students' prior learning and present feelings, foster collaborative learning, integrate major language skills, and encourage the…

  19. 31 CFR 337.6 - Conversions to book-entry.

    Science.gov (United States)

    2010-07-01

    ... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false Conversions to book-entry. 337.6... HOUSING ADMINISTRATION DEBENTURES Certificated Debentures § 337.6 Conversions to book-entry. Upon implementation of the book-entry debenture system, to be announced in advance by separate public notice, all...

  20. 32 CFR 643.11 - Rights of entry.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 4 2010-07-01 2010-07-01 true Rights of entry. 643.11 Section 643.11 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY (CONTINUED) REAL PROPERTY REAL ESTATE General § 643.11 Rights of entry. Pending the signing of the formal instrument, no right of entry will be granted unless authorized by the...

  1. 50 CFR 91.31 - Return of entries after contest.

    Science.gov (United States)

    2010-10-01

    ... 50 Wildlife and Fisheries 6 2010-10-01 2010-10-01 false Return of entries after contest. 91.31... (CONTINUED) MISCELLANEOUS PROVISIONS MIGRATORY BIRD HUNTING AND CONSERVATION STAMP CONTEST Post-Contest Procedures § 91.31 Return of entries after contest. (a) All entries will be returned by certified mail to...

  2. 19 CFR 143.16 - Substitution of warehouse entry.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 2 2010-04-01 2010-04-01 false Substitution of warehouse entry. 143.16 Section 143.16 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT... warehouse entry. The importer may substitute an entry for warehouse at any time within 1 year from the...

  3. 78 FR 38069 - Expansion of Global Entry to Additional Airports

    Science.gov (United States)

    2013-06-25

    ... Register on February 6, 2012 (77 FR 5681), promulgated the regulation to establish Global Entry as an... FR 17492.) Travelers who wish to participate in Global Entry must apply via the CBP Global Entry Web..., New York (JFK); George Bush Intercontinental Airport, Houston, Texas (IAH); Washington...

  4. Optimal firm growth under the threat of entry

    NARCIS (Netherlands)

    Kort, Peter; Wrzaczek, S.

    2015-01-01

    The paper studies the incumbent-entrant problem in a fully dynamic setting. We find that under an open-loop information structure the incumbent anticipates entry by overinvesting, whereas in the Markov perfect equilibrium the incumbent slightly underinvests in the period before the entry. The entry

  5. 32 CFR 809a.1 - Random installation entry point checks.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 6 2010-07-01 2010-07-01 false Random installation entry point checks. 809a.1... Entry Policy § 809a.1 Random installation entry point checks. The installation commander determines when, where, and how to implement random checks of vehicles or pedestrians. The commander conducts...

  6. 19 CFR 143.23 - Form of entry.

    Science.gov (United States)

    2010-04-01

    ... List of CFR Sections Affected, which appears in the Finding Aids section of the printed volume and on... (CONTINUED) SPECIAL ENTRY PROCEDURES Informal Entry § 143.23 Form of entry. Except for the types of... is prescribed by § 10.1 of this chapter; (c) Personal effects and tools of trade for which...

  7. Calcium-Dependent and Independent Mechanisms of Capsaicin Receptor (TRPV1)-Mediated Cytokine Production and Cell Death in Human Bronchial Epithelial Cells

    OpenAIRE

    Reilly, Christopher A.; Johansen, Mark E.; Lanza, Diane L.; Lee, Jeewoo; Lim, Ju-Ok; Yost, Garold S.

    2005-01-01

    Activation of the capsaicin receptor (VR1 or TRPV1) in bronchial epithelial cells by capsaicinoids and other vanilloids promotes pro-inflammatory cytokine production and cell death. The purpose of this study was to investigate the role of TRPV1-mediated calcium flux from extracellular sources as an initiator of these responses and to define additional cellular pathways that control cell death. TRPV1 antagonists and reduction of calcium concentrations in treatment solutions attenuated calcium ...

  8. Designing pathways

    DEFF Research Database (Denmark)

    Scheuer, John Damm

    2010-01-01

    The theoretical background in this chapter is organizational studies and especially theories about design and design processes in organizations. The concept of design is defined as a particular kind of work aimed at making arrangements in order to change existing situations into desired ones. The...... illustrative case example is the introduction of clinical pathways in a psychiatric department. The contribution to a general core of design research is the development of the concept of design work and a critical discussion of the role of technological rules in design work....

  9. Available hardware for automated entry control

    International Nuclear Information System (INIS)

    Automated entry control has become an increasingly important issue at facilities where budget constraints are limiting options for manned entry control points. Ongoing work at Sandia National Laboratories is attempting to establish a data base for use by facility security managers working the problem of how to maintain security on a limited budget. Sandia National Laboratories conducted a performance test of the following biometric verifiers: (1) voice verifier by Alpha Microsystems of Santa Ana, California; (2) signature dynamics verifier by Autosig Systems of Irving, Texas; (3) voice verifier by Ecco Industries of Danvers, Massachusetts (now International Electronics); (4) retinal pattern verifier by EyeDentify of Portland, Oregon; (5) fingerprint verifier by Identix of Sunnyvale, California; and (6) hand geometry verifier by Recognition Systems of San Jose, California

  10. Summary analysis of the Gemini entry aerodynamics

    Science.gov (United States)

    Whitnah, A. M.; Howes, D. B.

    1972-01-01

    The aerodynamic data that were derived in 1967 from the analysis of flight-generated data for the Gemini entry module are presented. These data represent the aerodynamic characteristics exhibited by the vehicle during the entry portion of Gemini 2, 3, 5, 8, 10, 11, and 12 missions. For the Gemini, 5, 8, 10, 11, and 12 missions, the flight-generated lift-to-drag ratios and corresponding angles of attack are compared with the wind tunnel data. These comparisons show that the flight generated lift-to-drag ratios are consistently lower than were anticipated from the tunnel data. Numerous data uncertainties are cited that provide an insight into the problems that are related to an analysis of flight data developed from instrumentation systems, the primary functions of which are other than the evaluation of flight aerodynamic performance.

  11. Tactile Data Entry for Extravehicular Activity

    Science.gov (United States)

    Adams, Richard J.; Olowin, Aaron B.; Hannaford, Blake; Sands, O Scott

    2012-01-01

    In the task-saturated environment of extravehicular activity (EVA), an astronaut's ability to leverage suit-integrated information systems is limited by a lack of options for data entry. In particular, bulky gloves inhibit the ability to interact with standard computing interfaces such as a mouse or keyboard. This paper presents the results of a preliminary investigation into a system that permits the space suit gloves themselves to be used as data entry devices. Hand motion tracking is combined with simple finger gesture recognition to enable use of a virtual keyboard, while tactile feedback provides touch-based context to the graphical user interface (GUI) and positive confirmation of keystroke events. In human subject trials, conducted with twenty participants using a prototype system, participants entered text significantly faster with tactile feedback than without (p = 0.02). The results support incorporation of vibrotactile information in a future system that will enable full touch typing and general mouse interactions using instrumented EVA gloves.

  12. Dependency of radon entry on pressure difference

    International Nuclear Information System (INIS)

    Radon levels, ventilation rate and pressure differences were monitored continuously in four apartment houses with different ventilation systems. Two of them were ventilated by mechanical exhaust, one by mechanical supply and exhaust, and one by natural ventilation. The two-storey houses were constructed from concrete elements on a slab and located on a gravel esker. It was surprising to find that increasing the ventilation rate increased levels of radon in the apartments. Increased ventilation caused increased outdoor-indoor pressure difference, which in turn increased the entry rate of radon and counteracted the diluting effect of ventilation. The increase was significant when the outdoor-indoor pressure difference exceeded 5 Pa. Especially in the houses with mechanical exhaust ventilation the pressure difference was the most important factor of radon entry rate, and contributed up to several hundred Bq m-3h-1. (Author)

  13. RTLS entry load relief parameter optimization

    Science.gov (United States)

    Crull, T. J.

    1975-01-01

    The results are presented of a study of a candidate load relief control law for use during the pullup phase of Return-to-Launch-Site (RTLS) abort entries. The control law parameters and cycle time which optimized performance of the normal load factor limiting phase (load relief phase) of an RTLS entry are examined. A set of control law gains, a smoothing parameter, and a normal force coefficient curve fit are established which resulted in good load relief performance considering the possible aerodynamic coefficient uncertainties defined. Also, the examination of various guidance cycle times revealed improved load relief performance with decreasing cycle time. A .5 second cycle provided smooth and adequate load relief in the presence of all the aerodynamic uncertainties examined.

  14. Data entry and error embedding system

    Science.gov (United States)

    Woo, Jr., John (Inventor); Woo, Daniel N. (Inventor)

    1998-01-01

    A data entry and error embedding system in which, first, a document is bitmapped and recorded in a first memory. Then, it is displayed, and portions of it to be replicated by data entry are underlayed by a window, into which window replicated data is entered in location and size such that it is juxtaposed just below that which is replicated, enhancing the accuracy of replication. Second, with this format in place, selected portions of the replicated data are altered by the insertion of character or word substitutions, thus the embedding of errors. Finally, a proofreader would endeavor to correct the error embedded data and a record of his or her changes recorded. In this manner, the skill level of the proofreader and accuracy of the data are computed.

  15. System for histogram entry, retrieval, and plotting

    International Nuclear Information System (INIS)

    This manual describes the systems for producing histograms and dot plots that were designed for use in connection with the Q general-purpose data-acquisition system. These systems allow for the creation of histograms; the entry, retrieval, and plotting of data in the form of histograms; and the dynamic display of scatter plots as data are acquired. Although the systems are designed for use with Q, they can also be used as a part of other applications. 3 figures

  16. Hex: dynamics and probabilistic text entry

    OpenAIRE

    J. Williamson; Murray-Smith, R.

    2005-01-01

    We present a gestural interface for entering text on a mobile device via continuous movements, with control based on feedback from a probabilistic language model. Text is represented by continuous trajectories over a hexagonal tessellation, and entry becomes a manual control task. The language model is used to infer user intentions and provide predictions about future actions, and the local dynamics adapt to reduce effort in entering probable text. This leads to an interface with a stable lay...

  17. Horizontal mergers, entry, and efficiency defences

    OpenAIRE

    Spector, David

    2002-01-01

    This paper addresses the effect of horizontal mergers on prices. It is shown that if firms compete in quantities and marginal costs are nondecreasing, any profitable merger failing to generate technological synergies must harm consumers through higher prices, irrespective of entry conditions in the industry. However this result does not hold if products are differentiated and firms compete in prices. The implications for merger policy are discussed.

  18. Export Discoveries, Diversification and Barriers to Entry

    OpenAIRE

    Klinger, Bailey; Lederman, Daniel

    2011-01-01

    The literature on the relationship between economic diversification and development established that diversification rises with development up to a point. Some have argued that market failures reduce private investments that are necessary to find out whether a new product can be exported profitably, thus implying that the threat of entry can reduce export discoveries and consequently hamper diversification. In parallel, the trade literature on the "extensive margin" of trade has focused on th...

  19. Contingency tables with uniformly bounded entries

    OpenAIRE

    Shapiro, Austin

    2011-01-01

    We consider nonnegative integer matrices with specified row and column sums and upper bounds on the entries. We show that the logarithm of the number of such matrices is approximated by a concave function of the row and column sums. We give efficiently computable estimators for this function, including one suggested by a maximum-entropy random model; we show that these estimators are asymptotically exact as the dimension of the matrices goes to infinity. We finish by showing that, for kappa >...

  20. Analysis of Ebola Virus Entry Into Macrophages

    OpenAIRE

    Dahlmann, F; Biedenkopf, N.; Babler, A; Jahnen-Dechent, W; Karsten, CB; Gnirß, K; Schneider, H; Wrensch, F; O'Callaghan, CA; Bertram, S. (Sabine); Herrler, G; Becker, S.; Pöhlmann, S; Hofmann-Winkler, H

    2015-01-01

    Ebolaviruses constitute a public health threat, particularly in Central and Western Africa. Host cell factors required for spread of ebolaviruses may serve as targets for antiviral intervention. Lectins, TAM receptor tyrosine kinases (Tyro3, Axl, Mer), T cell immunoglobulin and mucin domain (TIM) proteins, integrins, and Niemann-Pick C1 (NPC1) have been reported to promote entry of ebolaviruses into certain cellular systems. However, the factors used by ebolaviruses to invade macrophages, maj...

  1. Protease Inhibitors Targeting Coronavirus and Filovirus Entry

    OpenAIRE

    Zhou, Yanchen; Vedantham, Punitha; Lu, Kai; Agudelo, Juliet; Carrion, Ricardo; Nunneley, Jerritt W.; Barnard, Dale; Pöhlmann, Stefan; McKerrow, James H.; Renslo, Adam R; Simmons, Graham

    2015-01-01

    In order to gain entry into cells, diverse viruses, including Ebola virus, SARS-coronavirus and the emerging MERS-coronavirus, depend on activation of their envelope glycoproteins by host cell proteases. The respective enzymes are thus excellent targets for antiviral intervention. In cell culture, activation of Ebola virus, as well as SARS- and MERS-coronavirus can be accomplished by the endosomal cysteine proteases, cathepsin L (CTSL) and cathepsin B (CTSB). In addition, SARS- and MERS-coron...

  2. Spectrum licensing, policy instruments and market entry

    OpenAIRE

    Madden, Gary; Bohlin, Erik; Tran, Thien; Morey, Aaron

    2013-01-01

    Competition policy attempts to address the potential for market failure by encouraging competition in service markets. Often, in wireless communication service markets, national regulatory authorities seek to encourage entry via the spectrum assignment process. Instruments used include the assignment mode (auction or beauty contest), setting aside licenses and providing bidding (price and quantity) credits for potential entrants, and making more licenses (spectrum blocks) available than incum...

  3. Market Entry into Nigeria : Case study: Uros

    OpenAIRE

    Itoje, Tobore

    2016-01-01

    The purpose of this thesis is to look into the telecommunication market on a business-to-business basis for foreign companies like Uros with partnership. It focuses on the Nigerian telecommunication market and the possibilities for entry. The thesis could also be of help to any foreign companies that wants to enter into the telecommunication market in Nigeria. The main reason for Uros to enter into the Nigerian market is to expand their network, gain more international audience to their pr...

  4. Fixed-fee Pricing and Entry

    OpenAIRE

    Ryoko Oki

    2015-01-01

    This study considers the anti-competitive effect of fixed-fee pricing, such as the one seen in a recent antitrust case in Japan. We show that fixed-fee pricing has stronger exclusionary effect than the per-use pricing's exclusionary effect. However, the restriction on usage of fixed-fee pricing may have a welfare-decreasing effect, although the restriction promotes entry.

  5. Cellular Factors Implicated in Filovirus Entry

    OpenAIRE

    Suchita Bhattacharyya; Hope, Thomas J.

    2013-01-01

    Although filoviral infections are still occurring in different parts of the world, there are no effective preventive or treatment strategies currently available against them. Not only do filoviruses cause a deadly infection, but they also have the potential of being used as biological weapons. This makes it imperative to comprehensively study these viruses in order to devise effective strategies to prevent the occurrence of these infections. Entry is the foremost step in the filoviral replica...

  6. The calcium-signaling toolkit: Updates needed.

    Science.gov (United States)

    Dubois, Charlotte; Prevarskaya, Natalia; Vanden Abeele, Fabien

    2016-06-01

    Here, we review the role of Ca(2+) in apoptosis, namely that ER Ca(2+) depletion or a sustained elevation of cytosolic or mitochondrial Ca(2+) concentration are sufficient to trigger apoptosis. These concepts have emerged by the use of ER stressor agents that decrease the ER Ca(2+) pool by inhibiting SERCA pumps. However, aside from their well-known actions on Ca(2+) homeostasis disruption leading to apoptosis, new evidence show that some ER Ca(2+) modulators have significant implications in other Ca(2+)-mediated or Ca(2+)-independent pathways determining cell fate suggesting a more complex regulation of apoptosis by intracellular Ca(2+). Here, we discuss the crucial interplay between Ca(2+) mediated apoptosis, the Unfold Protein Response and autophagy determining cell fate, and the molecular compounds that have been used to depict these pathways. This review of the literature clearly shows the need for new inhibitors that do not interfere concomitantly with autophagy and Ca(2+) signaling. This article is part of a Special Issue entitled: Calcium and Cell Fate. Guest Editors: Jacques Haiech, Claus Heizmann, Joachim Krebs, Thierry Capiod and Olivier Mignen. PMID:26658643

  7. Combinations of physiologic estrogens with xenoestrogens alter calcium and kinase responses, prolactin release, and membrane estrogen receptor trafficking in rat pituitary cells

    Directory of Open Access Journals (Sweden)

    Watson Cheryl S

    2010-10-01

    Full Text Available Abstract Background Xenoestrogens such as alkylphenols and the structurally related plastic byproduct bisphenol A have recently been shown to act potently via nongenomic signaling pathways and the membrane version of estrogen receptor-α. Though the responses to these compounds are typically measured individually, they usually contaminate organisms that already have endogenous estrogens present. Therefore, we used quantitative medium-throughput screening assays to measure the effects of physiologic estrogens in combination with these xenoestrogens. Methods We studied the effects of low concentrations of endogenous estrogens (estradiol, estriol, and estrone at 10 pM (representing pre-development levels, and 1 nM (representing higher cycle-dependent and pregnancy levels in combinations with the same levels of xenoestrogens in GH3/B6/F10 pituitary cells. These levels of xenoestrogens represent extremely low contamination levels. We monitored calcium entry into cells using Fura-2 fluorescence imaging of single cells. Prolactin release was measured by radio-immunoassay. Extracellular-regulated kinase (1 and 2 phospho-activations and the levels of three estrogen receptors in the cell membrane (ERα, ERβ, and GPER were measured using a quantitative plate immunoassay of fixed cells either permeabilized or nonpermeabilized (respectively. Results All xenoestrogens caused responses at these concentrations, and had disruptive effects on the actions of physiologic estrogens. Xenoestrogens reduced the % of cells that responded to estradiol via calcium channel opening. They also inhibited the activation (phosphorylation of extracellular-regulated kinases at some concentrations. They either inhibited or enhanced rapid prolactin release, depending upon concentration. These latter two dose-responses were nonmonotonic, a characteristic of nongenomic estrogenic responses. Conclusions Responses mediated by endogenous estrogens representing different life stages are

  8. Analysis of Ebola Virus Entry Into Macrophages

    Science.gov (United States)

    Dahlmann, Franziska; Biedenkopf, Nadine; Babler, Anne; Jahnen-Dechent, Willi; Karsten, Christina B.; Gnirß, Kerstin; Schneider, Heike; Wrensch, Florian; O'Callaghan, Christopher A.; Bertram, Stephanie; Herrler, Georg; Becker, Stephan; Pöhlmann, Stefan; Hofmann-Winkler, Heike

    2015-01-01

    Ebolaviruses constitute a public health threat, particularly in Central and Western Africa. Host cell factors required for spread of ebolaviruses may serve as targets for antiviral intervention. Lectins, TAM receptor tyrosine kinases (Tyro3, Axl, Mer), T cell immunoglobulin and mucin domain (TIM) proteins, integrins, and Niemann-Pick C1 (NPC1) have been reported to promote entry of ebolaviruses into certain cellular systems. However, the factors used by ebolaviruses to invade macrophages, major viral targets, are poorly defined. Here, we show that mannose-specific lectins, TIM-1 and Axl augment entry into certain cell lines but do not contribute to Ebola virus (EBOV)-glycoprotein (GP)–driven transduction of macrophages. In contrast, expression of Mer, integrin αV, and NPC1 was required for efficient GP-mediated transduction and EBOV infection of macrophages. These results define cellular factors hijacked by EBOV for entry into macrophages and, considering that Mer and integrin αV promote phagocytosis of apoptotic cells, support the concept that EBOV relies on apoptotic mimicry to invade target cells. PMID:25877552

  9. Orion Entry, Descent, and Landing Simulation

    Science.gov (United States)

    Hoelscher, Brian R.

    2007-01-01

    The Orion Entry, Descent, and Landing simulation was created over the past two years to serve as the primary Crew Exploration Vehicle guidance, navigation, and control (GN&C) design and analysis tool at the National Aeronautics and Space Administration (NASA). The Advanced NASA Technology Architecture for Exploration Studies (ANTARES) simulation is a six degree-of-freedom tool with a unique design architecture which has a high level of flexibility. This paper describes the decision history and motivations that guided the creation of this simulation tool. The capabilities of the models within ANTARES are presented in detail. Special attention is given to features of the highly flexible GN&C architecture and the details of the implemented GN&C algorithms. ANTARES provides a foundation simulation for the Orion Project that has already been successfully used for requirements analysis, system definition analysis, and preliminary GN&C design analysis. ANTARES will find useful application in engineering analysis, mission operations, crew training, avionics-in-the-loop testing, etc. This paper focuses on the entry simulation aspect of ANTARES, which is part of a bigger simulation package supporting the entire mission profile of the Orion vehicle. The unique aspects of entry GN&C design are covered, including how the simulation is being used for Monte Carlo dispersion analysis and for support of linear stability analysis. Sample simulation output from ANTARES is presented in an appendix.

  10. Gated entry into the ciliary compartment.

    Science.gov (United States)

    Takao, Daisuke; Verhey, Kristen J

    2016-01-01

    Cilia and flagella play important roles in cell motility and cell signaling. These functions require that the cilium establishes and maintains a unique lipid and protein composition. Recent work indicates that a specialized region at the base of the cilium, the transition zone, serves as both a barrier to entry and a gate for passage of select components. For at least some cytosolic proteins, the barrier and gate functions are provided by a ciliary pore complex (CPC) that shares molecular and mechanistic properties with nuclear gating. Specifically, nucleoporins of the CPC limit the diffusional entry of cytosolic proteins in a size-dependent manner and enable the active transport of large molecules and complexes via targeting signals, importins, and the small G protein Ran. For membrane proteins, the septin protein SEPT2 is part of the barrier to entry whereas the gating function is carried out and/or regulated by proteins associated with ciliary diseases (ciliopathies) such as nephronophthisis, Meckel–Gruber syndrome and Joubert syndrome. Here, we discuss the evidence behind these models of ciliary gating as well as the similarities to and differences from nuclear gating. PMID:26472341

  11. Analysis of Ebola Virus Entry Into Macrophages.

    Science.gov (United States)

    Dahlmann, Franziska; Biedenkopf, Nadine; Babler, Anne; Jahnen-Dechent, Willi; Karsten, Christina B; Gnirß, Kerstin; Schneider, Heike; Wrensch, Florian; O'Callaghan, Christopher A; Bertram, Stephanie; Herrler, Georg; Becker, Stephan; Pöhlmann, Stefan; Hofmann-Winkler, Heike

    2015-10-01

    Ebolaviruses constitute a public health threat, particularly in Central and Western Africa. Host cell factors required for spread of ebolaviruses may serve as targets for antiviral intervention. Lectins, TAM receptor tyrosine kinases (Tyro3, Axl, Mer), T cell immunoglobulin and mucin domain (TIM) proteins, integrins, and Niemann-Pick C1 (NPC1) have been reported to promote entry of ebolaviruses into certain cellular systems. However, the factors used by ebolaviruses to invade macrophages, major viral targets, are poorly defined. Here, we show that mannose-specific lectins, TIM-1 and Axl augment entry into certain cell lines but do not contribute to Ebola virus (EBOV)-glycoprotein (GP)-driven transduction of macrophages. In contrast, expression of Mer, integrin αV, and NPC1 was required for efficient GP-mediated transduction and EBOV infection of macrophages. These results define cellular factors hijacked by EBOV for entry into macrophages and, considering that Mer and integrin αV promote phagocytosis of apoptotic cells, support the concept that EBOV relies on apoptotic mimicry to invade target cells. PMID:25877552

  12. Mars Exploration Entry, Descent and Landing Challenges

    Science.gov (United States)

    Braun, Robert D.; Manning, Robert M.

    2006-01-01

    The United States has successfully landed five robotic systems on the surface of Mars. These systems all had landed mass below 0.6 metric tons (t), had landed footprints on the order of hundreds of km and landed at sites below -1.4 km MOLA elevation due the need to perform entry, descent and landing operations in an environment with sufficient atmospheric density. At present, robotic exploration systems engineers are struggling with the challenges of increasing landed mass capability to 0.8 t while improving landed accuracy to tens of km and landing at a site as high as +2 km MOLA elevation for the Mars Science Laboratory project. Meanwhile, current plans for human exploration of Mars call for the landing of 40-80 t surface elements at scientifically interesting locations within close proximity (tens of m) of pre-positioned robotic assets. This paper summarizes past successful entry, descent and landing systems and approaches being developed by the robotic Mars exploration program to increased landed performance (mass, accuracy and surface elevation). In addition, the entry, descent and landing sequence for a human exploration system will be reviewed, highlighting the technology and systems advances required.

  13. Nuclear Chk1 prevents premature mitotic entry.

    Science.gov (United States)

    Matsuyama, Makoto; Goto, Hidemasa; Kasahara, Kousuke; Kawakami, Yoshitaka; Nakanishi, Makoto; Kiyono, Tohru; Goshima, Naoki; Inagaki, Masaki

    2011-07-01

    Chk1 inhibits the premature activation of the cyclin-B1-Cdk1. However, it remains controversial whether Chk1 inhibits Cdk1 in the centrosome or in the nucleus before the G2-M transition. In this study, we examined the specificity of the mouse monoclonal anti-Chk1 antibody DCS-310, with which the centrosome was stained. Conditional Chk1 knockout in mouse embryonic fibroblasts reduced nuclear but not centrosomal staining with DCS-310. In Chk1(+/myc) human colon adenocarcinoma (DLD-1) cells, Chk1 was detected in the nucleus but not in the centrosome using an anti-Myc antibody. Through the combination of protein array and RNAi technologies, we identified Ccdc-151 as a protein that crossreacted with DCS-310 on the centrosome. Mitotic entry was delayed by expression of the Chk1 mutant that localized in the nucleus, although forced immobilization of Chk1 to the centrosome had little impact on the timing of mitotic entry. These results suggest that nuclear but not centrosomal Chk1 contributes to correct timing of mitotic entry. PMID:21628425

  14. Cellular factors implicated in filovirus entry.

    Science.gov (United States)

    Bhattacharyya, Suchita; Hope, Thomas J

    2013-01-01

    Although filoviral infections are still occurring in different parts of the world, there are no effective preventive or treatment strategies currently available against them. Not only do filoviruses cause a deadly infection, but they also have the potential of being used as biological weapons. This makes it imperative to comprehensively study these viruses in order to devise effective strategies to prevent the occurrence of these infections. Entry is the foremost step in the filoviral replication cycle and different studies have reported the involvement of a myriad of cellular factors including plasma membrane components, cytoskeletal proteins, endosomal components, and cytosolic factors in this process. Signaling molecules such as the TAM family of receptor tyrosine kinases comprising of Tyro3, Axl, and Mer have also been implicated as putative entry factors. Additionally, filoviruses are suggested to bind to a common receptor and recent studies have proposed T-cell immunoglobulin and mucin domain 1 (TIM-1) and Niemann-Pick C1 (NPC1) as potential receptor candidates. This paper summarizes the existing literature on filoviral entry with a special focus on cellular factors involved in this process and also highlights some fundamental questions. Future research aimed at answering these questions could be very useful in designing novel antiviral therapeutics. PMID:23365575

  15. Cellular Factors Implicated in Filovirus Entry

    Directory of Open Access Journals (Sweden)

    Suchita Bhattacharyya

    2013-01-01

    Full Text Available Although filoviral infections are still occurring in different parts of the world, there are no effective preventive or treatment strategies currently available against them. Not only do filoviruses cause a deadly infection, but they also have the potential of being used as biological weapons. This makes it imperative to comprehensively study these viruses in order to devise effective strategies to prevent the occurrence of these infections. Entry is the foremost step in the filoviral replication cycle and different studies have reported the involvement of a myriad of cellular factors including plasma membrane components, cytoskeletal proteins, endosomal components, and cytosolic factors in this process. Signaling molecules such as the TAM family of receptor tyrosine kinases comprising of Tyro3, Axl, and Mer have also been implicated as putative entry factors. Additionally, filoviruses are suggested to bind to a common receptor and recent studies have proposed T-cell immunoglobulin and mucin domain 1 (TIM-1 and Niemann-Pick C1 (NPC1 as potential receptor candidates. This paper summarizes the existing literature on filoviral entry with a special focus on cellular factors involved in this process and also highlights some fundamental questions. Future research aimed at answering these questions could be very useful in designing novel antiviral therapeutics.

  16. "Caged calcium" in Aplysia pacemaker neurons. Characterization of calcium-activated potassium and nonspecific cation currents

    OpenAIRE

    1989-01-01

    We have studied calcium-activated potassium current, IK(Ca), and calcium-activated nonspecific cation current, INS(Ca), in Aplysia bursting pacemaker neurons, using photolysis of a calcium chelator (nitr-5 or nitr-7) to release "caged calcium" intracellularly. A computer model of nitr photolysis, multiple buffer equilibration, and active calcium extrusion was developed to predict volume-average and front-surface calcium concentration transients. Changes in arsenazo III absorbance were used to...

  17. Effect of Preharvest Calcium Treatments on Sweet Cherry Fruit Quality

    OpenAIRE

    Deniz EROGUL

    2014-01-01

    In this study, the effects of different foliar calcium compounds on fruit cracking and quality of sweet cherry variety ‘0900 Ziraat’ were investigated. Calcium caseinate, calcium chloride, calcium hydroxide and calcium nitrate were used as foliar sprays. Calcium applications reduced the cracking index 38% to 66% compared to cherries that did not receive foliar treatment. The most efficient applications for decreasing cracking were calcium hydroxide and calcium chloride. Calcium chloride and c...

  18. Stochastic Simulation of Cardiac Ventricular Myocyte Calcium Dynamics and Waves

    OpenAIRE

    Tuan, Hoang-Trong Minh; Williams, George S.B.; Chikando, Aristide C.; Sobie, Eric A.; Lederer, W. Jonathan; Jafri, M. Saleet

    2011-01-01

    A three dimensional model of calcium dynamics in the rat ventricular myocyte was developed to study the mechanism of calcium homeostasis and pathological calcium dynamics during calcium overload. The model contains 20,000 calcium release units (CRUs) each containing 49 ryanodine receptors. The model simulates calcium sparks with a realistic spontaneous calcium spark rate. It suggests that in addition to the calcium spark-based leak, there is an invisible calcium leak caused by the stochastic ...

  19. Rapid responses to reverse T₃ hormone in immature rat Sertoli cells: calcium uptake and exocytosis mediated by integrin.

    Directory of Open Access Journals (Sweden)

    Ana Paula Zanatta

    Full Text Available There is increasing experimental evidence of the nongenomic action of thyroid hormones mediated by receptors located in the plasma membrane or inside cells. The aim of this work was to characterize the reverse T₃ (rT₃ action on calcium uptake and its involvement in immature rat Sertoli cell secretion. The results presented herein show that very low concentrations of rT₃ are able to increase calcium uptake after 1 min of exposure. The implication of T-type voltage-dependent calcium channels and chloride channels in the effect of rT₃ was evidenced using flunarizine and 9-anthracene, respectively. Also, the rT₃-induced calcium uptake was blocked in the presence of the RGD peptide (an inhibitor of integrin-ligand interactions. Therefore, our findings suggest that calcium uptake stimulated by rT₃ may be mediated by integrin αvβ₃. In addition, it was demonstrated that calcium uptake stimulated by rT₃ is PKC and ERK-dependent. Furthermore, the outcomes indicate that rT₃ also stimulates cellular secretion since the cells manifested a loss of fluorescence after 4 min incubation, indicating an exocytic quinacrine release that seems to be mediated by the integrin receptor. These findings indicate that rT₃ modulates the calcium entry and cellular secretion, which might play a role in the regulation of a plethora of intracellular processes involved in male reproductive physiology.

  20. Aging and calcium as an environmental factor.

    Science.gov (United States)

    Fujita, T

    1985-12-01

    Calcium deficiency is a constant menace to land-abiding animals, including mammals. Humans enjoying exceptional longevity on earth are especially susceptible to calcium deficiency in old age. Low calcium and vitamin D intake, short solar exposure, decreased intestinal absorption, and falling renal function with insufficient 1,25(OH)2 vitamin D biosynthesis all contribute to calcium deficiency, secondary hyperparathyroidism, bone loss and possibly calcium shift from the bone to soft tissue, and from the extracellular to the intracellular compartment, blunting the sharp concentration gap between these compartments. The consequences of calcium deficiency might thus include not only osteoporosis, but also arteriosclerosis and hypertension due to the increase of calcium in the vascular wall, amyotrophic lateral sclerosis and senile dementia due to calcium deposition in the central nervous system, and a decrease in cellular function, because of blunting of the difference in extracellular-intracellular calcium, leading to diabetes mellitus, immune deficiency and others (Fig. 6). PMID:2943880

  1. Transport of Calcium Ions into Mitochondria.

    Science.gov (United States)

    Xu, Zhaolong; Zhang, Dayong; He, Xiaolan; Huang, Yihong; Shao, Hongbo

    2016-06-01

    To uptake calcium ions of mitochondria is of significant functional connotation for cells, because calcium ions in mitochondria are involved in energy production, regulatory signals transfer, and mitochondrial permeability transition pore opening and even programmed cell death of apoptosis, further playing more roles in plant productivity and quality. Cytoplasmic calcium ions access into outer mitochondrial membrane (OMM) from voltage dependent anion-selective channel (VDAC) and were absorbed into inner mitochondrial membrane (IMM) by mitochondrial calcium uniporter (MCU), rapid mitochondrial calcium uptake (RaM) or mitochondrial ryanodine receptor (mRyR). Although both mitochondria and the mechanisms of calcium transport have been extensively studied, but there are still long-standing or even new challenges. Here we review the history and recent discoveries of the mitochondria calcium ions channel complex involved calcium assimilation, and discuss the role of calcium ions into mitochondria. PMID:27252588

  2. Exporting Complex Digital Products: Motives and Entry Modes

    DEFF Research Database (Denmark)

    Rask, Morten

    When the product is digital, it will most often be distributed directly to the customer through the Internet, and therefore the entry modes, considered in this paper, are different flavors of the entry mode called direct export: Virtual export channel are generally understood as the entry mode for...... digital product providers. However other types of entry modes like what wee call direct digital export with F2F-sales, direct digital export with F2F-support and virtual sales subsidiary are entry modes that respond to a higher degree of pre- and after-sales complexity....

  3. Exporting Complex Digital Products: Motives and Entry Modes

    DEFF Research Database (Denmark)

    Rask, Morten

    2005-01-01

    When the product is digital, it will most often be distributed directly to the customer through the Internet, and therefore, the entry modes, considered in this paper, are different flavors of the entry mode called direct export: virtual export channel is generally understood as the entry mode for...... digital product providers. However, other types of entry modes like what we call direct digital export with F2F-sales, direct digital export with F2F-support, and virtual sales subsidiary are entry modes that respond to a higher degree of pre- and postsales complexity....

  4. Calcium-antagonists and islet function. Pt. 5

    International Nuclear Information System (INIS)

    R33711, a new drug with presumed potent calcium-antagonistic property, was found to suppress the insulinotropic action of glucose und gliclazide but not that of theophylline. A 0.2 μM concentration of R33711 was sufficient to abolish glucose-induced insulin release. At this concentration, R33711 inhibited the net uptake of 45Ca2+ by isolated islets, whether in the absence or presence of either glucose or sulfonylurea. In the isolated islets, R33711 failed to affect the glucose-stimulated production of lactate, the rate of 45Ca2+ efflux, the inhibitory action of glucose upon such an efflux and its increase in response to theophylline. These data are compatible with the view that R33711 inhibits entry of Ca2+ into the B-cell and that integrity of such an inward cationic movement usually plays a permissive role in the maintenance of the Ca2+-dependent insulin secretory process. (orig.)

  5. Molecular structure and pathophysiological roles of the Mitochondrial Calcium Uniporter.

    Science.gov (United States)

    Mammucari, Cristina; Raffaello, Anna; Vecellio Reane, Denis; Rizzuto, Rosario

    2016-10-01

    Mitochondrial Ca(2+) uptake regulates a wide array of cell functions, from stimulation of aerobic metabolism and ATP production in physiological settings, to induction of cell death in pathological conditions. The molecular identity of the Mitochondrial Calcium Uniporter (MCU), the highly selective channel responsible for Ca(2+) entry through the IMM, has been described less than five years ago. Since then, research has been conducted to clarify the modulation of its activity, which relies on the dynamic interaction with regulatory proteins, and its contribution to the pathophysiology of organs and tissues. Particular attention has been placed on characterizing the role of MCU in cardiac and skeletal muscles. In this review we summarize the molecular structure and regulation of the MCU complex in addition to its pathophysiological role, with particular attention to striated muscle tissues. This article is part of a Special Issue entitled: Mitochondrial Channels edited by Pierre Sonveaux, Pierre Maechler and Jean-Claude Martinou. PMID:26968367

  6. Radon entry rate analyses using in situ tracer gas method application

    International Nuclear Information System (INIS)

    Recently, the role of energy savings in indoor air quality deterioration has been extensively emphasised, predominantly in the context of significant air exchange rate reduction as a result of home energy retrofits. In case of refurbishment of existing buildings, the effect of energy-efficient technologies on indoor radon concentration is considerably complex and has to be carefully evaluated with respect to radon entry rate (RER) and air exchange rate alteration. For the purpose of detailed analysis of radon entry pathways, the unique infiltration experiment has been carried out using the tracer gas (N2O) method application in field conditions. Significant amount of experimental works has been done to provide an independent assessment of RER and air-exchange rate facilitating the analysis of fundamental factors influencing the indoor radon variations (e.g. indoor-outdoor pressure difference induced by wind, stack effect, heating, ventilation and operation of air-conditioning systems). (authors)

  7. Identification of entry inhibitors of Ebola virus pseudotyped vectors from a myxobacterial compound library.

    Science.gov (United States)

    Beck, Simon; Henß, Lisa; Weidner, Tatjana; Herrmann, Jennifer; Müller, Rolf; Chao, Yu-Kai; Grimm, Christian; Weber, Christopher; Sliva, Katja; Schnierle, Barbara S

    2016-08-01

    Myxobacteria produce secondary metabolites many of which were described to have various biological effects including anti-fungal, anti-bacterial and anti-viral activity. The majority of these metabolites are novel scaffolds with unique modes-of-action and hence might be potential leads for drug discovery. Here, we tested a myxobacterial natural product library for compounds with inhibitory activity against Ebola virus (EBOV). The assay was performed with a surrogate system using Ebola envelope glycoprotein (GP) pseudotyped lentiviral vectors. EBOV specificity was proven by counter-screening with vesicular stomatitis virus G protein pseudotyped vectors. Two compounds were identified that preferentially inhibited EBOV GP mediated cell entry: Chondramides that act on the actin skeleton but might be too toxic and noricumazole A, a potassium channel inhibitor, which might constitute a novel pathway to inhibit Ebola virus cell entry. PMID:27241689

  8. Optimizing calcium selective fluorimetric nanospheres.

    Science.gov (United States)

    Kisiel, Anna; Kłucińska, Katarzyna; Gniadek, Marianna; Maksymiuk, Krzysztof; Michalska, Agata

    2015-11-01

    Recently it was shown that optical nanosensors based on alternating polymers e.g. poly(maleic anhydride-alt-1-octadecene) were characterized by a linear dependence of emission intensity on logarithm of concentration over a few of orders of magnitude range. In this work we focus on the material used to prepare calcium selective nanosensors. It is shown that alternating polymer nanosensors offer competitive performance in the absence of calcium ionophore, due to interaction of the nanospheres building blocks with analyte ions. The emission increase corresponds to increase of calcium ions contents in the sample within the range from 10(-4) to 10(-1) M. Further improvement in sensitivity (from 10(-6) to 10(-1) M) and selectivity can be achieved by incorporating calcium ionophore in the nanospheres. The optimal results were obtained for core-shell nanospheres, where the core was prepared from poly(styrene-co-maleic anhydride) and the outer layer from poly(maleic anhydride-alt-1-octadecene). Thus obtained chemosensors were showing linear dependence of emission on logarithm of calcium ions concentration within the range from 10(-7) to 10(-1) M. PMID:26452839

  9. Isomorfic Substitutions of Calcium by Strontium in Calcium Hydroxyapatite

    International Nuclear Information System (INIS)

    By means of homogeneous precipitation it has been possible to synthesize crystalline solid solutions of calcium strontium hydroxyapatite from aqueous solutions. The lattice constants for the solid solutions were measured in the range Ca9Sr(PO4)6(OH)2 - CaSr9(PO4)6(OH)2. The investigations show that the discrimination of strontium against calcium is considerably smaller than reported elsewhere (1). Strontium is preferentially built into the c-axis direction of the apatite lattice

  10. Effect of anions or foods on absolute bioavailability of calcium from calcium salts in mice by pharmacokinetics

    OpenAIRE

    Ueda, Yukari; Taira, Zenei

    2013-01-01

    We studied the absolute bioavailability of calcium from calcium L-lactate in mice using pharmacokinetics, and reviewed the absolute bioavailability of calcium from three other calcium salts in mice previously studied: calcium chloride, calcium acetate, and calcium ascorbate. The results showed that calcium metabolism is linear between intravenous administration of 15 mg/kg and 30 mg/kg, and is not affected by anions. Results after oral calcium administration of 150 mg/kg showed that the intes...

  11. Impaired Cellular Bioenergetics Causes Mitochondrial Calcium Handling Defects in MT-ND5 Mutant Cybrids

    Science.gov (United States)

    Duchen, Michael R.

    2016-01-01

    Mutations in mitochondrial DNA (mtDNA) can cause mitochondrial disease, a group of metabolic disorders that affect both children and adults. Interestingly, individual mtDNA mutations can cause very different clinical symptoms, however the factors that determine these phenotypes remain obscure. Defects in mitochondrial oxidative phosphorylation can disrupt cell signaling pathways, which may shape these disease phenotypes. In particular, mitochondria participate closely in cellular calcium signaling, with profound impact on cell function. Here, we examined the effects of a homoplasmic m.13565C>T mutation in MT-ND5 on cellular calcium handling using transmitochondrial cybrids (ND5 mutant cybrids). We found that the oxidation of NADH and mitochondrial membrane potential (Δψm) were significantly reduced in ND5 mutant cybrids. These metabolic defects were associated with a significant decrease in calcium uptake by ND5 mutant mitochondria in response to a calcium transient. Inhibition of glycolysis with 2-deoxy-D-glucose did not affect cytosolic calcium levels in control cybrids, but caused an increase in cytosolic calcium in ND5 mutant cybrids. This suggests that glycolytically-generated ATP is required not only to maintain Δψm in ND5 mutant mitochondria but is also critical for regulating cellular calcium homeostasis. We conclude that the m.13565C>T mutation in MT-ND5 causes defects in both mitochondrial oxidative metabolism and mitochondrial calcium sequestration. This disruption of mitochondrial calcium handling, which leads to defects in cellular calcium homeostasis, may be an important contributor to mitochondrial disease pathogenesis. PMID:27110715

  12. Calcium release-activated calcium current in rat mast cells.

    Science.gov (United States)

    Hoth, M; Penner, R

    1993-06-01

    1. Whole-cell patch clamp recordings of membrane currents and fura-2 measurements of free intracellular calcium concentration ([Ca2+]i) were used to study the biophysical properties of a calcium current activated by depletion of intracellular calcium stores in rat peritoneal mast cells. 2. Calcium influx through an inward calcium release-activated calcium current (ICRAC) was induced by three independent mechanisms that result in store depletion: intracellular infusion of inositol 1,4,5-trisphosphate (InsP3) or extracellular application of ionomycin (active depletion), and intracellular infusion of calcium chelators (ethylene glycol bis-N,N,N',N'-tetraacetic acid (EGTA) or 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA)) to prevent reuptake of leaked-out calcium into the stores (passive depletion). 3. The activation of ICRAC induced by active store depletion has a short delay (4-14 s) following intracellular infusion of InsP3 or extracellular application of ionomycin. It has a monoexponential time course with a time constant of 20-30 s and, depending on the complementary Ca2+ buffer, a mean normalized amplitude (at 0 mV) of 0.6 pA pF-1 (with EGTA) and 1.1 pA pF-1 (with BAPTA). 4. After full activation of ICRAC by InsP3 in the presence of EGTA (10 mM), hyperpolarizing pulses to -100 mV induced an instantaneous inward current that decayed by 64% within 50 ms. This inactivation is probably mediated by [Ca2+]i, since the decrease of inward current in the presence of the fast Ca2+ buffer BAPTA (10 mM) was only 30%. 5. The amplitude of ICRAC was dependent on the extracellular Ca2+ concentration with an apparent dissociation constant (KD) of 3.3 mM. Inward currents were nonsaturating up to -200 mV. 6. The selectivity of ICRAC for Ca2+ was assessed by using fura-2 as the dominant intracellular buffer (at a concentration of 2 mM) and relating the absolute changes in the calcium-sensitive fluorescence (390 nm excitation) with the calcium current integral

  13. Calcium phosphate in catheter encrustation.

    Science.gov (United States)

    Cox, A J; Harries, J E; Hukins, D W; Kennedy, A P; Sutton, T M

    1987-02-01

    Encrusted catheters from nine female patients were the source of samples of deposits which were examined by X-ray diffraction, atomic absorption spectroscopy, infra-red spectroscopy and extended X-ray absorption fine structure (EXAFS) spectroscopy. In eight samples the only crystalline phase which could be clearly distinguished by X-ray diffraction was ammonium magnesium orthophosphate hexahydrate, NH4MgPO4 X 6H2O, which occurs naturally as the mineral struvite. However, atomic absorption spectroscopy revealed an appreciable concentration of calcium in all samples. Calcium phosphates have previously been detected in catheter deposits. Infra-red and EXAFS spectra were consistent with the calcium phosphate being present as a poorly crystalline hydroxyapatite. Thus the deposits appear to consist of a mixture of crystalline struvite and a form of hydroxyapatite which is not fully crystalline. PMID:3030487

  14. Molecular aspects of intestinal calcium absorption.

    Science.gov (United States)

    Diaz de Barboza, Gabriela; Guizzardi, Solange; Tolosa de Talamoni, Nori

    2015-06-21

    Intestinal Ca(2+) absorption is a crucial physiological process for maintaining bone mineralization and Ca(2+) homeostasis. It occurs through the transcellular and paracellular pathways. The first route comprises 3 steps: the entrance of Ca(2+) across the brush border membranes (BBM) of enterocytes through epithelial Ca(2+) channels TRPV6, TRPV5, and Cav1.3; Ca(2+) movement from the BBM to the basolateral membranes by binding proteins with high Ca(2+) affinity (such as CB9k); and Ca(2+) extrusion into the blood. Plasma membrane Ca(2+) ATPase (PMCA1b) and sodium calcium exchanger (NCX1) are mainly involved in the exit of Ca(2+) from enterocytes. A novel molecule, the 4.1R protein, seems to be a partner of PMCA1b, since both molecules co-localize and interact. The paracellular pathway consists of Ca(2+) transport through transmembrane proteins of tight junction structures, such as claudins 2, 12, and 15. There is evidence of crosstalk between the transcellular and paracellular pathways in intestinal Ca(2+) transport. When intestinal oxidative stress is triggered, there is a decrease in the expression of several molecules of both pathways that inhibit intestinal Ca(2+) absorption. Normalization of redox status in the intestine with drugs such as quercetin, ursodeoxycholic acid, or melatonin return intestinal Ca(2+) transport to control values. Calcitriol [1,25(OH)₂D₃] is the major controlling hormone of intestinal Ca(2+) transport. It increases the gene and protein expression of most of the molecules involved in both pathways. PTH, thyroid hormones, estrogens, prolactin, growth hormone, and glucocorticoids apparently also regulate Ca(2+) transport by direct action, indirect mechanism mediated by the increase of renal 1,25(OH)₂D₃ production, or both. Different physiological conditions, such as growth, pregnancy, lactation, and aging, adjust intestinal Ca(2+) absorption according to Ca(2+) demands. Better knowledge of the molecular details of intestinal Ca(2

  15. The effect of variable calcium and very low calcium diets on human calcium metabolism. Ph.D. Thesis. Final Report

    Science.gov (United States)

    Chu, J.

    1971-01-01

    The effects of a very low calcium diet, with variable high and low protein intake, on the dynamics of calcium metabolism and the mechanism of calciuretics, are examined. The experiment, using male subjects, was designed to study the role of intestinal calcium absorption on urinary calcium excretion, and the rate of production of endogeneously secreted calcium in the gastrointestinal tract. The study showed an average of 70% fractional absorption rate during very low calcium intake, and that a decrease in renal tubular reabsorption of calcium is responsible for calciuretic effects of high protein intake. The study also indicates that there is a tendency to develop osteoporosis after long periods of low calcium intake, especially with a concurrent high protein intake.

  16. How to Get Entry-Level Employment at the Top 100 Advertising Agencies.

    Science.gov (United States)

    Donnelly, William J.

    1994-01-01

    Reports on a survey which quantifies the entry-level market in top advertising agencies. Discusses employment projections, entry-level job distribution, source of entry-level employment, college degree of entry-level employees, academic major of entry-level employees, and entry-level assignments by major. Concludes that an advertising major is far…

  17. Entry properties and entry inhibitors of a human H7N9 influenza virus.

    Directory of Open Access Journals (Sweden)

    Youhui Si

    Full Text Available The recently identified human infections with a novel avian influenza H7N9 virus in China raise important questions regarding possible risk to humans. However, the entry properties and tropism of this H7N9 virus were poorly understood. Moreover, neuraminidase inhibitor resistant H7N9 isolates were recently observed in two patients and correlated with poor clinical outcomes. In this study, we aimed to elucidate the entry properties of H7N9 virus, design and evaluate inhibitors for H7N9 virus entry. We optimized and developed an H7N9-pseudotyped particle system (H7N9pp that could be neutralized by anti-H7 antibodies and closely mimicked the entry process of the H7N9 virus. Avian, human and mouse-derived cultured cells showed high, moderate and low permissiveness to H7N9pp, respectively. Based on influenza virus membrane fusion mechanisms, a potent anti-H7N9 peptide (P155-185-chol corresponding to the C-terminal ectodomain of the H7N9 hemagglutinin protein was successfully identified. P155-185-chol demonstrated H7N9pp-specific inhibition of infection with IC50 of 0.19 µM. Importantly, P155-185-chol showed significant suppression of A/Anhui/1/2013 H7N9 live virus propagation in MDCK cells and additive effects with NA inhibitors Oseltamivir and Zanamivir. These findings expand our knowledge of the entry properties of the novel H7N9 viruses, and they highlight the potential for developing a new class of inhibitors targeting viral entry for use in the next pandemic.

  18. Tumoral calcium pyrophosphate deposition disease

    International Nuclear Information System (INIS)

    A report of two patients in which a soft tissue mass, initially regarded as a malignant tumor, was shown to be the result of calcium pyrophosphate deposition disease. The first case, a woman aged 71 years, presented with a mass involving the right fifth finger. In the second case, also a women aged 71 years, the lesion involved the tissues adjacent to the right hip. Each lesion consisted of a mass of highly cellular tissue containing deposits of calcium pyrophosphate dihydrate crystals. The clinical, radiological, and pathological features of the two cases are compared with those of seven similar cases reported in the literature. (orig.)

  19. Effect of extracellular calcium on the additive effect of theophylline on the cardiac response to catecholamine

    Directory of Open Access Journals (Sweden)

    Shamkuwar Prashant

    2008-01-01

    Full Text Available At different extracellular calcium concentrations, the positive inotropic effect of isoproterenol and isoproterenol in combination with theophylline, a phosphodiesterase inhibitor have been evaluated in the isolated frog heart and the isolated guinea pig left atria to investigate whether extracellular calcium produces any effect on the additive effect of the theophylline on the cardiac response to catecholamine. Cumulative dose response study of isoproterenol and isoproterenol in presence of theophylline at different extracellular calcium concentration was performed. The study revealed an increase in additive effect of theophylline on the cardiac response to catecholamine with increase in extracellular calcium concentration, but increase in extracellular calcium concentration decreased the myocardial responsiveness to additive effect of theophylline and isoproterenol combination. The mechanism of positive inotropic effect of isoproterenol and in combination with theophylline involves increase in intracellular cAMP by different pathways and extracellular calcium produces positive inotropic effect by initiating the interaction between the contractile proteins actin and myosin. The study revealed that an increase in the concentration of extracellular calcium increased the additive effect of theophylline and isoproterenol combination, but a decrease in the myocardial responsiveness was observed.

  20. Visualization of Golgia apparatus as an intracellular calcium store by laser scanning confocal microscope

    Institute of Scientific and Technical Information of China (English)

    CUIJIE; YANLI; 等

    1995-01-01

    Using laser scanning confocal microscopy,we have found that the in cells loaded with fluo-3/AM,highest intracellular Ca2+ in the perinuclear region is associated with the Golgi apparatus.The spatiotemporal subcellular distribution of Ca2+ in living human fibroblasts exposing to calcium-free medium in response to agonists has been investigated.PDGF,which releases Ca2+ from intracellular stores by inositol(1,4,5)-trisphosphate pathway ,produced a biphasic transient rise in intracellular calcium.The initial rise was resulted from a direct release of calcium from the golgi apparatus.Calcium could be also released from and reaccumulated into the Golgi apparatus by the stimulation of thapsigargin,an inhibitor of the Ca2+ transport ATPase of intracellular calcium store,Permeablizing the plasma membrane by 10μM digitonin resulted in the calcium release from the Golgi apparatus and depletion of the internal calcium store.These results suggest that the Golgi apparatus plays a role in Ca2+ regulation in signal transduction.

  1. Calcium control of gene regulation in rat hippocampal neuronal cultures.

    Science.gov (United States)

    Pinato, Giulietta; Pegoraro, Silvia; Iacono, Giovanni; Ruaro, Maria Elisabetta; Torre, Vincent

    2009-09-01

    Blockage of GABA-A receptors in hippocampal neuronal cultures triggers synchronous bursts of spikes initiating neuronal plasticity, partly mediated by changes of gene expression. By using specific pharmacological blockers, we have investigated which sources of Ca2+ entry primarily control changes of gene expression induced by 20 microM gabazine applied for 30 min (GabT). Intracellular Ca2+ transients were monitored with Ca2+ imaging while recording electrical activity with patch clamp microelectrodes. Concomitant transcription profiles were obtained using Affymetrix oligonucleotide microarrays and confirmed with quantitative RT-PCR. Blockage of NMDA receptors with 2-amino-5-phosphonovaleric acid (APV) did not reduce significantly somatic Ca2+ transients, which, on the contrary, were reduced by selective blockage of L, N, and P/Q types voltage gated calcium channels (VGCCs). Therefore, we investigated changes of gene expression in the presence of blockers of NMDA receptors and L, N, and P/Q VGCCs. Our results show that: (i) among genes upregulated by GabT, there are genes selectively dependent on NMDA activation, genes selectively dependent on L-type VGCCs and genes dependent on the activation of both channels; (ii) the majority of genes requires the concomitant activation of NMDA receptors and Ca2+ entry through VGCCs; (iii) blockage of N and P/Q VGCCs has an effect similar but not identical to blockage of L-type VGCCs. PMID:19441076

  2. Blockade of L-type calcium channel in myocardium and calcium-induced contractions of vascular smooth muscle by by CPU 86017

    Institute of Scientific and Technical Information of China (English)

    De-zai DAI; Hui-juan HU; Jing ZHAO; Xue-mei HAO; Dong-mei YANG; Pei-ai ZHOU; Cai-hong WU

    2004-01-01

    AIM: To assess the blockade by CPU 86017 on the L-type calcium channels in the myocardium and on the Ca2+related contractions of vascular smooth muscle. METHODS: The whole-cell patch-clamp was applied to investigate the blocking effect of CPU 86017 on the L-type calcium current in isolated guinea pig myocytes and contractions by KC1 or phenylephrine (Phe) of the isolated rat tail arteries were measured. RESULTS: Suppression of the L-type current of the isolated myocytes by CPU 86017 was moderate, in time- and concentration-dependent manner and with no influence on the activation and inactivation curves. The IC50 was 11.5 μmol/L. Suppressive effect of CPU 86017 on vaso-contractions induced by KC1 100 mmol/L, phenylephrine I μmol/Lin KH solution (phase 1),Ca2+ free KH solution ( phase 2), and by addition of CaCI2 into Ca2+-free KH solution (phase 3) were observed. The IC50 to suppress vaso-contractions by calcium entry via the receptor operated channel (ROC) and Voltage-dependent channel (VDC) was 0.324 μmol/L and 16.3 μmol/L, respectively. The relative potency of CPU 86017 to suppress vascular tone by Ca2+ entry through ROC and VDC is 1/187 of prazosin and 1/37 of verapamil, respectively.CONCLUSION: The blocking effects of CPU 86017 on the L-type calcium channel of myocardium and vessel are moderate and non-selective. CPU 86017 is approximately 50 times more potent in inhibiting ROC than VDC.

  3. Spermidine-Induced Improvement of Reconsolidation of Memory Involves Calcium-Dependent Protein Kinase in Rats

    Science.gov (United States)

    Girardi, Bruna Amanda; Ribeiro, Daniela Aymone; Signor, Cristiane; Muller, Michele; Gais, Mayara Ana; Mello, Carlos Fernando; Rubin, Maribel Antonello

    2016-01-01

    In this study, we determined whether the calcium-dependent protein kinase (PKC) signaling pathway is involved in the improvement of fear memory reconsolidation induced by the intrahippocampal administration of spermidine in rats. Male Wistar rats were trained in a fear conditioning apparatus using a 0.4-mA footshock as an unconditioned stimulus.…

  4. MicroRNA-30 family members regulate calcium/calcineurin signaling in podocytes

    Science.gov (United States)

    Wu, Junnan; Zheng, Chunxia; Wang, Xiao; Yun, Shifeng; Zhao, Yue; Liu, Lin; Lu, Yuqiu; Ye, Yuting; Zhu, Xiaodong; Zhang, Changming; Shi, Shaolin; Liu, Zhihong

    2015-01-01

    Calcium/calcineurin signaling is critical for normal cellular physiology. Abnormalities in this pathway cause many diseases, including podocytopathy; therefore, understanding the mechanisms that underlie the regulation of calcium/calcineurin signaling is essential. Here, we showed that critical components of calcium/calcineurin signaling, including TRPC6, PPP3CA, PPP3CB, PPP3R1, and NFATC3, are the targets of the microRNA-30 family (miR-30s). We found that these 5 genes are highly expressed as mRNA, but the level of the proteins is low in normal podocytes. Conversely, protein levels were markedly elevated in podocytes from rats treated with puromycin aminonucleoside (PAN) and from patients with focal segmental glomerulosclerosis (FSGS). In both FSGS patients and PAN-treated rats, miR-30s were downregulated in podocytes. In cultured podocytes, PAN or a miR-30 sponge increased TRPC6, PPP3CA, PPP3CB, PPP3R1, and NFATC3 expression; calcium influx; intracellular Ca2+ concentration; and calcineurin activity. Moreover, NFATC3 nuclear translocation, synaptopodin degradation, integrin β3 (ITGB3) activation, and actin fiber loss, which are downstream of calcium/calcineurin signaling, were induced by miR-30 reduction but blocked by the calcineurin inhibitor FK506. Podocyte-specific expression of the miR-30 sponge in mice increased calcium/calcineurin pathway component protein expression and calcineurin activity. The mice developed podocyte foot process effacement and proteinuria, which were prevented by FK506. miR-30s also regulated calcium/calcineurin signaling in cardiomyocytes. Together, our results identify miR-30s as essential regulators of calcium/calcineurin signaling. PMID:26436650

  5. Precursors and pathways to adolescent prostitution in Taiwan.

    Science.gov (United States)

    Hwang, Shu-Ling; Bedford, Olwen

    2003-05-01

    This paper identifies the major precursors and pathways to prostitution for contemporary Taiwanese girls and the socioeconomic and cultural changes that have facilitated the shift in pathways over the past 10 years. Special attention is paid to the case of Taiwanese aborigines, who have particularly suffered systemic disruption due to prostitution. Analysis of case files and interviews provide quantitative and qualitative data that highlight the role of filial piety and the shift from indenture to runaway as the major pathway in Taiwan. Discussion includes relation of these findings to juvenile entry into prostitution in other countries, directions for future research, and policy recommendations for Taiwan's government. PMID:12908127

  6. Complex formation ions calcium with macromolecules pectin

    International Nuclear Information System (INIS)

    In clause the mechanism of sorption of ions of calcium by macromolecules of pectin is opened. Is shown, that the linkage of ions of calcium descends on acid bunches of pectin, and process carries cooperative character

  7. Dairy Dilemma: Are You Getting Enough Calcium?

    Science.gov (United States)

    ... Dairy Dilemma Dairy Dilemma Are You Getting Enough Calcium? You may be avoiding dairy products because of ... But dairy products are a major source of calcium, vitamin D and other nutrients that are important ...

  8. Calcium, vitamin D, and your bones

    Science.gov (United States)

    ... can break easily, even without an obvious injury. Vitamin D helps your body absorb calcium. Eat foods that provide the right amounts of calcium, vitamin D, and protein. This kind of diet will give ...

  9. Flight Path Characteristics for Re entry Trajectories

    Directory of Open Access Journals (Sweden)

    S. K. Gurtu

    1972-07-01

    Full Text Available Approximate analytical solutions on velocity, range, deceleration, maximum deceleration, distance and time of flight, etc. are obtained for object entry in a planetary atmosphere when (i rate of change of velocity is proportional to the nth power of the velocity, and (ii rate of change of altitude is proportional to the pth power of the velocity. Loh's results for constant deceleration flight and constant rate of change of decent flight are obtained as particular cases. Finally, trajectory characteristics are obtained rate of change of range flight.

  10. Reference pricing with endogenous generic entry

    OpenAIRE

    Brekke, Kurt R.; Canta, Chiara; Straume, Odd Rune

    2015-01-01

    In this paper we study the effect of reference pricing on pharmaceutical prices and ex-penditures when generic entry is endogenously determined. We develop a Salop-type model where a brand-name producer competes with generic producers in terms of prices. In the market there are two types of consumers: (i) brand biased consumers who choose between brand-name and generic drugs, and (ii) brand neutral consumers who choose between the different generic drugs. We find that, for a given number of ...

  11. Radon entry into a simple test structure

    DEFF Research Database (Denmark)

    Andersen, C.E.; Søgaard-Hansen, J.; Majborn, B.

    1992-01-01

    A simple test structure for studies of radon entry into houses has been constructed at a field site at Riso National Laboratory. It consists of a 40 1, stainless-steel cylinder placed in a 0.52 m deep quadratic excavation with a side length of 2.4 m. The excavation is lined with an airtight...... cylinder and in selected locations in the soil. In this paper, the test structure is described, and initial results concerning the transport of soil gas and radon under steady-state conditions are reported. It is found that the soil in the vicinity of the structure is partially depleted with respect to...

  12. About Pascal's tetrahedron with hypercomplex entries

    Science.gov (United States)

    Cruz, C.; Falcão, M. I.; Malonek, H. R.

    2013-10-01

    It is evident, that the properties of monogenic polynomials in (n + 1)-real variables significantly depend on the generators e1,e2,...,en of the underlying 2n-dimensional Clifford algebra Cℓ0,n over R and their interactions under multiplication. The case of n = 3 is studied through the consideration of Pascal's tetrahedron with hypercomplex entries as special case of the general Pascal simplex for arbitrary n, which represents a useful geometric arrangement of all possible products. The different layers Lk of Pascal's tetrahedron (or pyramid) are built by ordered symmetric products contained in the trinomial expansion of (e1+e2+e3)k,k = 0,1,....

  13. Polar fluxes of calcium ions and growth of plant tissues

    International Nuclear Information System (INIS)

    The authors studied the action exerted by auxin transport inhibitors (2,3,5-triiodobenzoic acid, 10-4 M; 1-N-naphthylphthalamic acid, 10-4 M), inhibitors of membrane-bound ATPases (sodium orthovanadate, 10-4 M; diethylstilbestrol, 10-5 M), and a blocker of Ca-channels (verapamil, 1.3 x 10-4 M) on growth processes (lengthwise growth, the gravitropic response) and translocation of 45Ca in segments of corn (Zea mays L.) coleoptiles and pea (Pisum sativum L.) internodes. Calcium in vertically oriented and gravistimulated segments was polarly translocated in a direction opposite the vector of gravitational force. It is hypothesized that the polar fluxes of Ca2+ ions which arise in tissues with a change in position of the plant organism in space are capable of correcting the direction of active basipetal transport of IAA and thereby able to induce polarization of growth processes. In studying transport of Ca2+ ions on plasmalemma vesicles with the aid of chlorotetracycline, it was found that creation of a potassium diffusion potential on the membrane (as a results of valinomycin treatment) induces entry of calcium into the vesicles. Since this effect was removed by verapamil and ruthenium red, it is postulated that potential-dependent Ca-channels are present on the plasma membrane of corn coleoptile cells

  14. Calcium channel blockers and Alzheimer's disease

    Institute of Scientific and Technical Information of China (English)

    Yi Tan; Yulin Deng; Hong Qing

    2012-01-01

    Alzheimer's disease is characterized by two pathological hallmarks: amyloid plaques and neurofi-brillary tangles. In addition, calcium homeostasis is disrupted in the course of human aging. Recent research shows that dense plaques can cause functional alteration of calcium signals in mice with Alzheimer's disease. Calcium channel blockers are effective therapeutics for treating Alzheimer's disease. This review provides an overview of the current research of calcium channel blockers in-volved in Alzheimer's disease therapy.

  15. Calcium channel blockers and Alzheimer's disease★

    OpenAIRE

    Tan, Yi; Deng, Yulin; Qing, Hong

    2012-01-01

    Alzheimer's disease is characterized by two pathological hallmarks: amyloid plaques and neurofibrillary tangles. In addition, calcium homeostasis is disrupted in the course of human aging. Recent research shows that dense plaques can cause functional alteration of calcium signals in mice with Alzheimer's disease. Calcium channel blockers are effective therapeutics for treating Alzheimer's disease. This review provides an overview of the current research of calcium channel blockers involved in...

  16. Teaching Calcium-Induced Calcium Release in Cardiomyocytes Using a Classic Paper by Fabiato

    Science.gov (United States)

    Liang, Willmann

    2008-01-01

    This teaching paper utilizes the materials presented by Dr. Fabiato in his review article entitled "Calcium-induced release of calcium from the cardiac sarcoplasmic reticulum." In the review, supporting evidence of calcium-induced calcium release (CICR) is presented. Data concerning potential objections to the CICR theory are discussed as well. In…

  17. Electrophysical properties of calcium orthovanadate

    International Nuclear Information System (INIS)

    The electron conductivity, dielectric permeability and magnetic susceptibility of calcium orthovanadate are studied. It is shown that structural transformations bring about changes in the nature of electrophysical properties of Ca3(VO4)2 and cause the charge redistribution in VO43- anion groups

  18. Development Challenges of Game-Changing Entry System Technologies From Concept to Mission Infusion

    Science.gov (United States)

    Venkatapathy, Ethiraj; Beck, Robin; Ellerby, Donald; Feldman, Jay; Gage, Peter; Munk, Michelle; Wercinski, Paul

    2016-01-01

    NASA's Space Technology Mission Directorate (STMD) and the Game Changing Development Program (GCDP) were created to develop new technologies. This paper describes four entry system technologies that are funded by the GCDP and summarizes the lessons learned during the development. The investments are already beginning to show success, mission infusion pathways after five years of existence. It is hoped that our experience and observations, drawn from projects supported by the GCD program/STMD, Orion and SMD can help current and future technology development projects. Observations on fostering a culture of success and on constraints that limit greater success are also provided.

  19. 21 CFR 582.1217 - Calcium phosphate.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Calcium phosphate. 582.1217 Section 582.1217 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Additives § 582.1217 Calcium phosphate. (a) Product. Calcium phosphate (mono-, di-, and tribasic)....

  20. 21 CFR 182.1217 - Calcium phosphate.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Calcium phosphate. 182.1217 Section 182.1217 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR... Substances § 182.1217 Calcium phosphate. (a) Product. Calcium phosphate (mono-, di-, and tribasic)....