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Sample records for mataga tadashi okada

  1. An archival study on the fusion researches in Japan from 1965 to 1986. An interview with Sekiguchi Tadashi

    Energy Technology Data Exchange (ETDEWEB)

    Nisio, Sigeko; Uematsu, Eisui [Nihon Univ., Tokyo (Japan). Coll. of Science and Technology; Obayashi, Haruo [National Inst. for Fusion Science, Toki, Gifu (Japan)] [and others

    2001-12-01

    We here report an archival study undertaken by the method of an interview with Sekiguchi Tadashi, Professor Emeritus at the University of Tokyo. The theme covers the circumstances of the fusion research during the period (1965-1976) when fusion project was launched in Japan, and during the period (1970-1986) when JT-60 was initiated and subsequently developed. This interview was arranged as a part of the collaborative works organized with the Data and Planning Center of NIFS since 1999. (author)

  2. Okadaic acid: the archetypal serine/threonine protein phosphatase inhibitor.

    Science.gov (United States)

    Dounay, A B; Forsyth, C J

    2002-11-01

    As the first recognized member of the "okadaic acid class" of phosphatase inhibitors, the marine natural product okadaic acid is perhaps the most well-known member of a diverse array of secondary metabolites that have emerged as valuable probes for studying the roles of various cellular protein serine/threonine phosphatases. This review provides a historical perspective on the role that okadaic acid has played in stimulating a broad spectrum of modern scientific research as a result of the natural product's ability to bind to and inhibit important classes of protein serine / threonine phosphatases. The relationships between the structure and biological activities of okadaic acid are briefly reviewed, as well as the structural information regarding the particular cellular receptors protein phosphatases 1 (PP1) and 2A. Laboratory syntheses of okadaic acid and its analogs are thoroughly reviewed. Finally, an interpretation of the critical contacts observed between okadaic acid and PP1 by X-ray crystallography is provided, and specific molecular recognition hypotheses that are testable via the synthesis and assay of non-natural analogs of okadaic acid are suggested.

  3. Okadaic acid: more than a diarrheic toxin.

    Science.gov (United States)

    Valdiglesias, Vanessa; Prego-Faraldo, María Verónica; Pásaro, Eduardo; Méndez, Josefina; Laffon, Blanca

    2013-10-31

    Okadaic acid (OA) is one of the most frequent and worldwide distributed marine toxins. It is easily accumulated by shellfish, mainly bivalve mollusks and fish, and, subsequently, can be consumed by humans causing alimentary intoxications. OA is the main representative diarrheic shellfish poisoning (DSP) toxin and its ingestion induces gastrointestinal symptoms, although it is not considered lethal. At the molecular level, OA is a specific inhibitor of several types of serine/threonine protein phosphatases and a tumor promoter in animal carcinogenesis experiments. In the last few decades, the potential toxic effects of OA, beyond its role as a DSP toxin, have been investigated in a number of studies. Alterations in DNA and cellular components, as well as effects on immune and nervous system, and even on embryonic development, have been increasingly reported. In this manuscript, results from all these studies are compiled and reviewed to clarify the role of this toxin not only as a DSP inductor but also as cause of alterations at the cellular and molecular levels, and to highlight the relevance of biomonitoring its effects on human health. Despite further investigations are required to elucidate OA mechanisms of action, toxicokinetics, and harmful effects, there are enough evidences illustrating its toxicity, not related to DSP induction, and, consequently, supporting a revision of the current regulation on OA levels in food.

  4. Okadaic Acid: More than a Diarrheic Toxin

    Directory of Open Access Journals (Sweden)

    Josefina Méndez

    2013-10-01

    Full Text Available Okadaic acid (OA is one of the most frequent and worldwide distributed marine toxins. It is easily accumulated by shellfish, mainly bivalve mollusks and fish, and, subsequently, can be consumed by humans causing alimentary intoxications. OA is the main representative diarrheic shellfish poisoning (DSP toxin and its ingestion induces gastrointestinal symptoms, although it is not considered lethal. At the molecular level, OA is a specific inhibitor of several types of serine/threonine protein phosphatases and a tumor promoter in animal carcinogenesis experiments. In the last few decades, the potential toxic effects of OA, beyond its role as a DSP toxin, have been investigated in a number of studies. Alterations in DNA and cellular components, as well as effects on immune and nervous system, and even on embryonic development, have been increasingly reported. In this manuscript, results from all these studies are compiled and reviewed to clarify the role of this toxin not only as a DSP inductor but also as cause of alterations at the cellular and molecular levels, and to highlight the relevance of biomonitoring its effects on human health. Despite further investigations are required to elucidate OA mechanisms of action, toxicokinetics, and harmful effects, there are enough evidences illustrating its toxicity, not related to DSP induction, and, consequently, supporting a revision of the current regulation on OA levels in food.

  5. An archival study on the nuclear fusion research in Japan later half of 1980's. An interview with SEKIGUCHI Tadashi, Professor Emeritus at the University of Tokyo

    Energy Technology Data Exchange (ETDEWEB)

    Nisio, Sigeko; Uematsu, Eisui [Nihon Univ., College of Science and Technology, Funabashi, Chiba (Japan); Obayashi, Haruo [National Inst. for Fusion Science, Toki, Gifu (Japan)] [and others

    2003-05-01

    An interview record with SEKIGUCHI Tadashi, Professor Emeritus at The University of Tokyo, on the nuclear fusion researches in Japan later half of 1980's is given. The major topics concerned are: activities of Science Council of Japan, the establishment of the Japan Society of Plasma Science and Nuclear Fusion Research, the history of establishing National Institute for Fusion Science, and effects of Grant-in-Aid for Scientific Research, and others. (author)

  6. Identification of Dynamic Changes in Proteins Associated with the Cellular Cytoskeleton after Exposure to Okadaic Acid

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    Peter Roepstorff

    2013-05-01

    Full Text Available Exposure of cells to the diarrhetic shellfish poison, okadaic acid, leads to a dramatic reorganization of cytoskeletal architecture and loss of cell-cell contact. When cells are exposed to high concentrations of okadaic acid (100–500 nM, the morphological rearrangement is followed by apoptotic cell death. Okadaic acid inhibits the broad acting Ser/Thr protein phosphatases 1 and 2A, which results in hyperphosphorylation of a large number of proteins. Some of these hyperphosphorylated proteins are most likely key players in the reorganization of the cell morphology induced by okadaic acid. We wanted to identify these phosphoproteins and searched for them in the cellular lipid rafts, which have been found to contain proteins that regulate cytoskeletal dynamics and cell adhesion. By using stable isotope labeling by amino acids in cell culture cells treated with okadaic acid (400 nM could be combined with control cells before the isolation of lipid rafts. Protein phosphorylation events and translocations induced by okadaic acid were identified by mass spectrometry. Okadaic acid was shown to regulate the phosphorylation status and location of proteins associated with the actin cytoskeleton, microtubules and cell adhesion structures. A large number of these okadaic acid-regulated proteins have previously also been shown to be similarly regulated prior to cell proliferation and migration. Our results suggest that okadaic acid activates general cell signaling pathways that induce breakdown of the cortical actin cytoskeleton and cell detachment.

  7. Identification of dynamic changes in proteins associated with the cellular cytoskeleton after exposure to okadaic acid

    DEFF Research Database (Denmark)

    Opsahl, Jill A; Ljostveit, Sonja; Solstad, Therese

    2013-01-01

    Exposure of cells to the diarrhetic shellfish poison, okadaic acid, leads to a dramatic reorganization of cytoskeletal architecture and loss of cell-cell contact. When cells are exposed to high concentrations of okadaic acid (100-500 nM), the morphological rearrangement is followed by apoptotic c...

  8. Teater peab alati proovima leida uut / Toshiki Okada ; intervjueerinud Evelyn Raudsepp

    Index Scriptorium Estoniae

    Okada, Toshiki

    2011-01-01

    20. aprillist 6. maini Tallinnas toimuva rahvusvahelise etenduskunstide festivali POT kaugema külalise jaapani teatritrupi Chelfitsch looja, dramaturgi ja lavastaja Toshiki Okada mõtteid tööst teatris

  9. Physico-chemical analysis of fish pond water in Okada and its ...

    African Journals Online (AJOL)

    ONOS

    2010-09-06

    Sep 6, 2010 ... African Journal of Biotechnology Vol. 9(36), pp. ... Water samples were collected from concrete and earthen fish ponds in different locations in Okada and its environs, Edo ..... industrial effluent for aquaculture-a case study.

  10. Selection and identification of DNA aptamers against okadaic acid for biosensing application.

    Science.gov (United States)

    Eissa, Shimaa; Ng, Andy; Siaj, Mohamed; Tavares, Ana C; Zourob, Mohammed

    2013-12-17

    This work describes the selection and identification of DNA aptamers that bind with high affinity and specificity to okadaic acid (OA), a lipophilic marine biotoxin that accumulates in shellfish. The aptamers selected using systematic evolution of ligands by exponential enrichment (SELEX) exhibited dissociation constants in the nanomolar range. The aptamer with the highest affinity was then used for the fabrication of a label-free electrochemical biosensor for okadaic acid detection. The aptamer was first immobilized on the gold electrode by a self-assembly approach through Au-S interaction. The binding of okadaic acid to the aptamer immobilized on the electrode surface induces an alteration of the aptamer conformation causing a significant decrease in the electron-transfer resistance monitored by electrochemical impedance spectroscopy. The aptasensor showed a linear range for the concentrations of OA between 100 pg/mL and 60 ng/mL with a detection limit of 70 pg/mL. The dissociation constant of okadaic acid with the aptamer immobilized on the electrode surface showed good agreement with that determined using fluorescence assay in solution. Moreover, the aptasensor did not show cross-reactivity toward toxins with structures similar to okadaic acid such as dinophysis toxin-1 and 2 (DTX-1, DTX-2). Further biosensing applications of the selected aptamers are expected to offer promising alternatives to the traditional analytical and immunological methods for OA detection.

  11. Diverse bacterial PKS sequences derived from okadaic acid-producing dinoflagellates.

    Science.gov (United States)

    Perez, Roberto; Liu, Li; Lopez, Jose; An, Tianying; Rein, Kathleen S

    2008-05-22

    Okadaic acid (OA) and the related dinophysistoxins are isolated from dinoflagellates of the genus Prorocentrum and Dinophysis. Bacteria of the Roseobacter group have been associated with okadaic acid producing dinoflagellates and have been previously implicated in OA production. Analysis of 16S rRNA libraries reveals that Roseobacter are the most abundant bacteria associated with OA producing dinoflagellates of the genus Prorocentrum and are not found in association with non-toxic dinoflagellates. While some polyketide synthase (PKS) genes form a highly supported Prorocentrum clade, most appear to be bacterial, but unrelated to Roseobacter or Alpha-Proteobacterial PKSs or those derived from other Alveolates Karenia brevis or Crytosporidium parvum.

  12. Okadaic acid inhibits cell growth and photosynthetic electron transport in the alga Dunaliella tertiolecta

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    Perreault, Francois; Matias, Marcelo Seleme; Oukarroum, Abdallah [Department of Chemistry, Universite du Quebec a Montreal, 2101, Rue Jeanne Mance, Montreal, QC, Canada H2X 2J6 (Canada); Matias, William Gerson [Department of Chemistry, Universite du Quebec a Montreal, 2101, Rue Jeanne Mance, Montreal, QC, Canada H2X 2J6 (Canada); Laboratorio de Toxicologia Ambiental, LABTOX, Depto. de Engenharia Sanitaria e Ambiental, Universidade Federal de Santa Catarina, Campus Universitario, CEP: 88040-970, Florianopolis, SC (Brazil); Popovic, Radovan, E-mail: popovic.radovan@uqam.ca [Department of Chemistry, Universite du Quebec a Montreal, 2101, Rue Jeanne Mance, Montreal, QC, Canada H2X 2J6 (Canada)

    2012-01-01

    Okadaic acid (OA), which is produced by several dinoflagellate species, is a phycotoxin known to induce a decrease of biomass production in phytoplankton. However, the mechanisms of OA cytotoxicity are still unknown in microalgae. In this study, we exposed the green microalga Dunaliella tertiolecta to OA concentrations of 0.05 to 0.5 {mu}M in order to evaluate its effects on cell division, reactive oxygen species production and photosynthetic electron transport. After 72 h of treatment under continuous illumination, OA concentrations higher than 0.10 {mu}M decreased culture cell density, induced oxidative stress and inhibited photosystem II electron transport capacity. OA effect in D. tertiolecta was strongly light dependent since no oxidative stress was observed when D. tertiolecta was exposed to OA in the dark. In the absence of light, the effect of OA on culture cell density and photosystem II activity was also significantly reduced. Therefore, light appears to have a significant role in the toxicity of OA in microalgae. Our results indicate that the site of OA interaction on photosynthetic electron transport is likely to be at the level of the plastoquinone pool, which can lead to photo-oxidative stress when light absorbed by the light-harvesting complex of photosystem II cannot be dissipated via photochemical pathways. These findings allowed for a better understanding of the mechanisms of OA toxicity in microalgae. - Highlights: Black-Right-Pointing-Pointer Exposition of Dunaliella tertiolecta to okadaic acid in light conditions results in reactive oxygen species formation. Black-Right-Pointing-Pointer Inhibition of photosystem II is dependent on oxidative stress and effects of okadaic acid on the plastoquinone pool. Black-Right-Pointing-Pointer Oxidative stress and inhibition of photosynthesis increase okadaic acid effect on cell density in light conditions. Black-Right-Pointing-Pointer Okadaic acid induces toxicity in algae via both light-dependent and light

  13. Diverse Bacterial PKS Sequences Derived From Okadaic Acid-Producing Dinoflagellates

    Directory of Open Access Journals (Sweden)

    Kathleen S. Rein

    2008-05-01

    Full Text Available Okadaic acid (OA and the related dinophysistoxins are isolated from dinoflagellates of the genus Prorocentrum and Dinophysis. Bacteria of the Roseobacter group have been associated with okadaic acid producing dinoflagellates and have been previously implicated in OA production. Analysis of 16S rRNA libraries reveals that Roseobacter are the most abundant bacteria associated with OA producing dinoflagellates of the genus Prorocentrum and are not found in association with non-toxic dinoflagellates. While some polyketide synthase (PKS genes form a highly supported Prorocentrum clade, most appear to be bacterial, but unrelated to Roseobacter or Alpha-Proteobacterial PKSs or those derived from other Alveolates Karenia brevis or Crytosporidium parvum.

  14. Sulfated diesters of okadaic acid and DTX-1: Self-protective precursors of diarrhetic shellfish poisoning (DSP) toxins.

    Science.gov (United States)

    Hu, Tingmo; LeBlanc, Patricia; Burton, Ian W; Walter, John A; McCarron, Pearse; Melanson, Jeremy E; Strangman, Wendy K; Wright, Jeffrey L C

    2017-03-01

    Many toxic secondary metabolites used for defense are also toxic to the producing organism. One important way to circumvent toxicity is to store the toxin as an inactive precursor. Several sulfated diesters of the diarrhetic shellfish poisoning (DSP) toxin okadaic acid have been reported from cultures of various dinoflagellate species belonging to the genus Prorocentrum. It has been proposed that these sulfated diesters are a means of toxin storage within the dinoflagellate cell, and that a putative enzyme mediated two-step hydrolysis of sulfated diesters such as DTX-4 and DTX-5 initially leads to the formation of diol esters and ultimately to the release of free okadaic acid. However, only one diol ester and no sulfated diesters of DTX-1, a closely related DSP toxin, have been isolated leading some to speculate that this toxin is not stored as a sulfated diester and is processed by some other means. DSP components in organic extracts of two large scale Prorocentrum lima laboratory cultures have been investigated. In addition to the usual suite of okadaic acid esters, as well as the free acids okadaic acid and DTX-1, a group of corresponding diol- and sulfated diesters of both okadaic acid and DTX-1 have now been isolated and structurally characterized, confirming that both okadaic acid and DTX-1 are initially formed in the dinoflagellate cell as the non-toxic sulfated diesters. Copyright © 2017. Published by Elsevier B.V.

  15. Okadaic acid and trifluoperazine enhance Agrobacterium-mediated transformation in eastern white pine.

    Science.gov (United States)

    Tang, Wei; Lin, Jinxing; Newton, Ronald J

    2007-05-01

    Mature zygotic embryos of recalcitrant Christmas tree species eastern white pine (Pinus strobus L.) were used as explants for Agrobacterium tumefaciens strain GV3101-mediated transformation using the uidA (beta-Glucuronidase) gene as a reporter. Influence of the time of sonication and the concentrations of protein phosphatase inhibitor (okadaic acid) and kinase inhibitor (trifluoperazine) on Agrobacterium-mediated transformation have been evaluated. A high transformation frequency was obtained after embryos were sonicated for 45-50 s, or treated with 1.5-2.0 microM okadaic acid or treated with 100-200 microM trifluoperazine, respectively. Protein phosphatase and kinase inhibitors enhance Agrobacterium-mediated transformation in eastern white pine. A 2-3.5-fold higher rate of hygromycin-resistant callus was obtained with an addition of 2 microM okadaic acid or 150 microM trifluoperazine or sonicated embryos for 45 s. Stable integration of the uidA gene in the plant genome of eastern white pine was confirmed by polymerase chain reaction (PCR), Southern and northern blot analyses. These results demonstrated that a stable and enhanced transformation system has been established in eastern white pine and this system would provide an opportunity to transfer economically important genes into this Christmas tree species.

  16. Contribution of mdr1b-type P-glycoprotein to okadaic acid resistance in rat pituitary GH3 cells.

    Science.gov (United States)

    Ritz, V; Marwitz, J; Sieder, S; Ziemann, C; Hirsch-Ernst, K I; Quentin, I; Steinfelder, H J

    1999-08-01

    Okadaic acid as well as other, structurally different, inhibitors of serine/threonine phosphatases 1 and 2A induce apoptosis in pituitary GH3 cells. Incubation with stepwise raised concentrations of okadaic acid resulted in the isolation of cells that were increasingly less sensitive to the cytotoxic effect of this agent. After about 18 months cells were selected that survived at 300 nM okadaic acid, which is about 30 times the initially lethal concentration. This study revealed that a major pharmacokinetic mechanism underlying cell survival was the development of a P-glycoprotein-mediated multidrug resistance (MDR) phenotype. The increase in mRNA levels of the mdr1b P-glycoprotein isoform correlated with the extent of drug resistance. Functional assays revealed that increasing drug resistance was paralleled by a decreased accumulation of rhodamine 123, a fluorescent dye which is a substrate of mdr1-mediated efflux activity. Resistance could be abolished by structurally different chemosensitizers of P-glycoprotein function like verapamil and reserpine but not by the leukotriene receptor antagonist MK571 which is a modulator of the multidrug resistance-associated protein (MRP). Okadaic acid resistance included cross-resistance to other cytotoxic agents that are substrates of mdr1-type P-glycoproteins, like doxorubicin and actinomycin D, but not to non-substrates of mdr1, e.g. cytosine arabinoside. Thus, functional as well as biochemical features support the conclusion that okadaic acid is a substrate of the mdr1-mediated efflux activity in rat pituitary GH3 cells. Maintenance of resistance after withdrawal of okadaic acid as well as metaphase spreads of 100 nM okadaic acid-resistant cells suggested a stable MDR genotype without indications for the occurrence of extrachromosomal amplifications, e.g. double minute chromosomes.

  17. Role of bone marrow mesenchymal stem cells in repair of neural cell injury induced by okadaic acid

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    Jia-jing LIU

    2017-06-01

    Full Text Available Objective To study whether the human bone marrow mesenchymal stem cells (HBMSCs can repair damaged neural cells induced by okadaic acid (OA. Methods Neuroblastoma cell line SH-SY5Y cells were used to incubate with 20nmol/L okadaic acid for 24h, establishing Alzheimer's Disease cell model; Three groups were set up: normal group, okadaic acid -damaged (OA-damaged group, hBMSCs -treatment group. The cells were injured for 24h with 20nmol/L OA in OA-damaged group, and treated with conditioned medium obtaining hBMSCs for 24h after 24h OA injury in the treatment group. Then CCK-8 was used for detecting cell vitality, immune fluorescence dyed microtubules and microfilaments for determining the dendritic cell length and fluorescence intensity, in addition, Western blotting for analyzing the protein level of phosphorylated tau and total tau proteins. Results Okadaic acid damaged SH-SY5Y cells, contributed to shrinkage, collapse, cavitation of the SH-SY5Y cell body, dendritic shortening and fracture, and irregular arrangement of microtubule microfilaments; while BMSCs conditioned medium made SH- SY5Y cell body become round and longer, dendrites restored, and microtubules and microfilaments arranged regularly, fluorescence intensity enhanced. Meanwhile,it also down-regulated the level of OA-induced tau phosphorylation. Conclusion hBMSCs have repair effects on the neural cell damage induced by okadaic acid. DOI: 10.11855/j.issn.0577-7402.2017.05.04

  18. Targets and Effects of Yessotoxin, Okadaic Acid and Palytoxin: A Differential Review

    Directory of Open Access Journals (Sweden)

    Enzo Ottaviani

    2010-03-01

    Full Text Available In this review, we focus on processes, organs and systems targeted by the marine toxins yessotoxin (YTX, okadaic acid (OA and palytoxin (PTX. The effects of YTX and their basis are analyzed from data collected in the mollusc Mytilus galloprovincialis, the annelid Enchytraeus crypticus, Swiss CD1 mice and invertebrate and vertebrate cell cultures. OA and PTX, two toxins with a better established mode of action, are analyzed with regard to their effects on development. The amphibian Xenopus laevis is used as a model, and the Frog Embryo Teratogenesis Assay-Xenopus (FETAX as the experimental protocol.

  19. Stathmin inhibition enhances okadaic acid-induced mitotic arrest: a potential role for stathmin in mitotic exit.

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    Mistry, S J; Atweh, G F

    2001-08-17

    Stathmin is a microtubule-destabilizing phosphoprotein that plays a critical role in the regulation of mitosis. The microtubule-depolymerizing activity of stathmin is lost upon phosphorylation in mitosis. Although the role of phosphorylation of stathmin by p34(cdc2) kinase in the assembly of the mitotic spindle is well established, the role of dephosphorylation of stathmin in mitosis is unknown. In this study, we tested the hypothesis that dephosphorylation of stathmin may be critically important for the depolymerization of the mitotic spindle and the exit from mitosis. We compared the effects of okadaic acid, a specific inhibitor of serine/threonine protein phosphatases, on different parameters of mitotic progression in the presence or absence of stathmin deficiency. Because okadaic acid prevents dephosphorylation of stathmin and results in accumulation of the inactive phosphorylated form, exposure to okadaic acid would be expected to have a more profound effect on mitosis in the presence of relative stathmin deficiency. We found that inhibition of stathmin expression results in increased sensitivity to the antimitotic effects of okadaic acid. This was reflected by increased growth inhibition associated with mitotic arrest. A vast majority of the stathmin-inhibited cells were found to be arrested in late metaphase/anaphase and had severe mitotic spindle abnormalities. Exposure to okadaic acid also resulted in a bigger ratio of polymerized/unpolymerized tubulin in stathmin-inhibited cells relative to control cells. Because the only difference between the control and the stathmin-inhibited cells is the deficiency of stathmin in the latter, the increased susceptibility of the stathmin-inhibited cells to okadaic acid-induced mitotic arrest implies a role for stathmin in the later stages of mitosis.

  20. Use of Okadaic Acid to Identify Relevant Phosphoepitopes in Pathology: A Focus on Neurodegeneration

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    Jesús Avila

    2013-05-01

    Full Text Available Protein phosphorylation is involved in the regulation of a wide variety of physiological processes and is the result of a balance between protein kinase and phosphatase activities. Biologically active marine derived compounds have been shown to represent an interesting source of novel compounds that could modify that balance. Among them, the marine toxin and tumor promoter, okadaic acid (OA, has been shown as an inhibitor of two of the main cytosolic, broad-specificity protein phosphatases, PP1 and PP2A, thus providing an excellent cell-permeable probe for examining the role of protein phosphorylation, and PP1 and PP2A in particular, in any physiological or pathological process. In the present work, we review the use of okadaic acid to identify specific phosphoepitopes mainly in proteins relevant for neurodegeneration. We will specifically highlight those cases of highly dynamic phosphorylation-dephosphorylation events and the ability of OA to block the high turnover phosphorylation, thus allowing the detection of modified residues that could be otherwise difficult to identify. Finally, its effect on tau hyperhosphorylation and its relevance in neurodegenerative pathologies such as Alzheimer’s disease and related dementia will be discussed.

  1. Okadaic acid

    DEFF Research Database (Denmark)

    Danielsen, E Michael; Hansen, Gert H; Severinsen, Mai C K

    2014-01-01

    endosomes (TWEEs) occurred unimpeded in the presence of OA, FM condensed in larger subapical structures by 1 h, implying a perturbed endosomal trafficking/maturation. The fluorescent lysosomotropic agent Lysotracker revealed induction of large lysosomal structures by OA. Endocytosis from the brush border...... was studied at the electron microscopic level using the membrane-impermeable marker Ruthenium Red (RR). Like FM dye, RR was taken up into TWEEs and multivesicular bodies (MVBs). However, OA induced the formation of a large number of lamellar bodies (LBs), a type of lysosome-related organelles. LBs...... are the hallmark of phospholipidosis, a pathological condition characterized by lysosomal phospholipid accumulation. Phospholipidosis is observed in acquired lysosomal storage diseases and is induced by a large number of cationic amphiphilic drugs. Unlike the latter, however, OA does not act by accumulating...

  2. Mass spectrometric analysis of the marine lipophilic biotoxins pectenotoxin-2 and okadaic acid by four different types of mass spectrometers

    NARCIS (Netherlands)

    Gerssen, A.; Mulder, P.P.J.; Rhijn, van J.A.; Boer, de J.

    2008-01-01

    The performances of four different mass spectrometers [triple-quadrupole (TQ), time-of-flight (ToF), quadrupole ToF (Q-ToF) and ion trap (IT)] for the detection of the marine lipophilic toxins pectenotoxin-2 (PTX2) and okadaic acid (OA) were investigated. The spectral data obtained with the differen

  3. Microencapsulation of okadaic acid as a tool for studying the accumulation of DSP toxins in mussels.

    Science.gov (United States)

    Rossignoli, Araceli E; Fernández, David; Acosta, Carmen P; Blanco, Juan

    2011-02-01

    The possibility and effectiveness of microencapsulation of okadaic acid (OA) in gelatin-acacia microcapsules has been studied. The encapsulation efficiency was higher than 33%. The microcapsules were shown to be very stable, not leaching more than 9% of the encapsulated OA in a 20-h period. OA from the microcapsules was absorbed by the mussels very efficiently, accumulating--after 3 days of feeding and one of depuration--65% of the OA in microcapsules and 22% of the total OA used at the beginning of the microencapsulation process. These efficiencies and the possibility of encapsulating single DSP toxins and derivatives constitute a valuable tool for the study of the accumulation and biotransformation of DSP toxins in bivalves.

  4. Identification of okadaic acid binding protein 2 in reconstituted sponge cell clusters from Halichondria okadai and its contribution to the detoxification of okadaic acid.

    Science.gov (United States)

    Konoki, Keiichi; Okada, Kayo; Kohama, Mami; Matsuura, Hiroki; Saito, Kaori; Cho, Yuko; Nishitani, Goh; Miyamoto, Tomofumi; Fukuzawa, Seketsu; Tachibana, Kazuo; Yotsu-Yamashita, Mari

    2015-12-15

    Okadaic acid (OA) and OA binding protein 2 (OABP2) were previously isolated from the marine sponge Halichondria okadai. Because the amino acid sequence of OABP2 is completely different from that of protein phosphatase 2A, a well-known target of OA, we have been investigating the production and function of OABP2. In the present study, we hypothesized that OABP2 plays a role in the detoxification of OA in H. okadai and that the OA concentrations are in proportional to the OABP2 concentrations in the sponge specimens. Based on the OA concentrations and the OABP2 concentrations in the sponge specimens collected in various places and in different seasons, however, we could not determine a positive correlation between OA and OABP2. We then attempted to determine distribution of OA and OABP2 in the sponge specimen. When the mixture of dissociated sponge cells and symbiotic species were separated with various pore-sized nylon meshes, most of the OA and OABP2 was detected from the same 0-10 μm fraction. Next, when sponge cell clusters were prepared from a mixture of dissociated sponge cells and symbiotic species in the presence of penicillin and streptomycin, we identified the 18S rDNA of H. okadai and the gene of OABP2 in the analysis of genomic DNA but could not detect OA by LC-MS/MS. We thus concluded that the sponge cells express OABP2, and that OA was not apparently present in the sponge cells but could be colocalized with OABP2 in the sponge cells at a concentration less than the limit of detection.

  5. Crystal Structure of Okadaic Acid Binding Protein 2.1: A Sponge Protein Implicated in Cytotoxin Accumulation.

    Science.gov (United States)

    Ehara, Haruhiko; Makino, Marie; Kodama, Koichiro; Konoki, Keiichi; Ito, Takuhiro; Sekine, Shun-ichi; Fukuzawa, Seketsu; Yokoyama, Shigeyuki; Tachibana, Kazuo

    2015-07-06

    Okadaic acid (OA) is a marine polyether cytotoxin that was first isolated from the marine sponge Halichondria okadai. OA is a potent inhibitor of protein serine/threonine phosphatases (PP) 1 and 2A, and the structural basis of phosphatase inhibition has been well investigated. However, the role and mechanism of OA retention in the marine sponge have remained elusive. We have solved the crystal structure of okadaic acid binding protein 2.1 (OABP2.1) isolated from H. okadai; it has strong affinity for OA and limited sequence homology to other proteins. The structure revealed that OABP2.1 consists of two α-helical domains, with the OA molecule deeply buried inside the protein. In addition, the global fold of OABP2.1 was unexpectedly similar to that of aequorin, a jellyfish photoprotein. The presence of structural homologues suggested that, by using similar protein scaffolds, marine invertebrates have developed diverse survival systems adapted to their living environments.

  6. Production of a soluble single-chain variable fragment antibody against okadaic acid and exploration of its specific binding.

    Science.gov (United States)

    He, Kuo; Zhang, Xiuyuan; Wang, Lixia; Du, Xinjun; Wei, Dong

    2016-06-15

    Okadaic acid is a lipophilic marine algal toxin commonly responsible for diarrhetic shellfish poisoning (DSP). Outbreaks of DSP have been increasing and are of worldwide public health concern; therefore, there is a growing demand for more rapid, reliable, and economical analytical methods for the detection of this toxin. In this study, anti-okadaic acid single-chain variable fragment (scFv) genes were prepared by cloning heavy and light chain genes from hybridoma cells, followed by fusion of the chains via a linker peptide. An scFv-pLIP6/GN recombinant plasmid was constructed and transformed into Escherichia coli for expression, and the target scFv was identified with IC-CLEIA (chemiluminescent enzyme immunoassay). The IC15 was 0.012 ± 0.02 μg/L, and the IC50 was 0.25 ± 0.03 μg/L. The three-dimensional structure of the scFv was simulated with computer modeling, and okadaic acid was docked to the scFv model to obtain a putative structure of the binding complex. Two predicted critical amino acids, Ser32 and Thr187, were then mutated to verify this theoretical model. Both mutants exhibited significant loss of binding activity. These results help us to understand this specific scFv-antigen binding mechanism and provide guidance for affinity maturation of the antibody in vitro. The high-affinity scFv developed here also has potential for okadaic acid toxin detection.

  7. Combined Effects of Lipophilic Phycotoxins (Okadaic Acid, Azapsiracid-1 and Yessotoxin on Human Intestinal Cells Models

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    Pierre-Jean Ferron

    2016-02-01

    Full Text Available Phycotoxins are monitored in seafood because they can cause food poisonings in humans. Phycotoxins do not only occur singly but also as mixtures in shellfish. The aim of this study was to evaluate the in vitro toxic interactions of binary combinations of three lipophilic phycotoxins commonly found in Europe (okadaic acid (OA, yessotoxin (YTX and azaspiracid-1 (AZA-1 using the neutral red uptake assay on two human intestinal cell models, Caco-2 and the human intestinal epithelial crypt-like cells (HIEC. Based on the cytotoxicity of individual toxins, we studied the interactions between toxins in binary mixtures using the combination index-isobologram equation, a method widely used in pharmacology to study drug interactions. This method quantitatively classifies interactions between toxins in mixtures as synergistic, additive or antagonistic. AZA-1/OA, and YTX/OA mixtures showed increasing antagonism with increasing toxin concentrations. In contrast, the AZA-1/YTX mixture showed increasing synergism with increasing concentrations, especially for mixtures with high YTX concentrations. These results highlight the hazard potency of AZA-1/YTX mixtures with regard to seafood intoxication.

  8. Intracerebroventricular administration of okadaic acid induces hippocampal glucose uptake dysfunction and tau phosphorylation.

    Science.gov (United States)

    Broetto, Núbia; Hansen, Fernanda; Brolese, Giovana; Batassini, Cristiane; Lirio, Franciane; Galland, Fabiana; Dos Santos, João Paulo Almeida; Dutra, Márcio Ferreira; Gonçalves, Carlos-Alberto

    2016-06-01

    Intraneuronal aggregates of neurofibrillary tangles (NFTs), together with beta-amyloid plaques and astrogliosis, are histological markers of Alzheimer's disease (AD). The underlying mechanism of sporadic AD remains poorly understood, but abnormal hyperphosphorylation of tau protein is suggested to have a role in NFTs genesis, which leads to neuronal dysfunction and death. Okadaic acid (OKA), a strong inhibitor of protein phosphatase 2A, has been used to induce dementia similar to AD in rats. We herein investigated the effect of intracerebroventricular (ICV) infusion of OKA (100 and 200ng) on hippocampal tau phosphorylation at Ser396, which is considered an important fibrillogenic tau protein site, and on glucose uptake, which is reduced early in AD. ICV infusion of OKA (at 200ng) induced a spatial cognitive deficit, hippocampal astrogliosis (based on GFAP increment) and increase in tau phosphorylation at site 396 in this model. Moreover, we observed a decreased glucose uptake in the hippocampal slices of OKA-treated rats. In vitro exposure of hippocampal slices to OKA altered tau phosphorylation at site 396, without any associated change in glucose uptake activity. Taken together, these findings further our understanding of OKA neurotoxicity, in vivo and vitro, particularly with regard to the role of tau phosphorylation, and reinforce the importance of the OKA dementia model for studying the neurochemical alterations that may occur in AD, such as NFTs and glucose hypometabolism.

  9. In Vitro Acylation of Okadaic Acid in the Presence of Various Bivalves’ Extracts

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    Mari Yotsu-Yamashita

    2013-01-01

    Full Text Available The dinoflagellate Dinophysis spp. is responsible for diarrhetic shellfish poisoning (DSP. In the bivalves exposed to the toxic bloom of the dinoflagellate, dinophysistoxin 3 (DTX3, the 7-OH acylated form of either okadaic acid (OA or DTX1, is produced. We demonstrated in vitro acylation of OA with palmitoyl CoA in the presence of protein extract from the digestive gland, but not other tissues of the bivalve Mizuhopecten yessoensis. The yield of 7-O-palmitoyl OA reached its maximum within 2 h, was the highest at 37 °C followed by 28 °C, 16 °C and 4 °C and was the highest at pH 8 in comparison with the yields at pH 6 and pH 4. The transformation also proceeded when the protein extract was prepared from the bivalves Corbicula japonica and Crassostrea gigas. The OA binding protein OABP2 identified in the sponge Halichondria okadai was not detected in the bivalve M. yessoensis, the bivalve Mytilus galloprovincialis and the ascidian Halocynthia roretzi, though they are known to accumulate diarrhetic shellfish poisoning toxins. Since DTX3 does not bind to protein phosphatases 1 and 2A, the physiological target for OA and DTXs in mammalian cells, the acylation of DSP toxins would be related to a detoxification mechanism for the bivalve species.

  10. New Invertebrate Vectors for PST, Spirolides and Okadaic Acid in the North Atlantic

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    Luis M. Botana

    2013-06-01

    Full Text Available The prevalence of poisoning events due to harmful algal blooms (HABs has declined during the last two decades through monitoring programs and legislation, implemented mainly for bivalves. However, new toxin vectors and emergent toxins pose a challenge to public health. Several locations on the Portuguese coast were surveyed between 2009 and 2010 for three distinct biotoxin groups [saxitoxin (PST, spirolide (SPX and okadaic acid (OA], in 14 benthic species of mollusks and echinoderms. Our main goals were to detect new vectors and unravel the seasonal and geographical patterns of these toxins. PSTs were analyzed by the Lawrence method, SPXs by LC-MS/MS, and OA by LC-MS/MS and UPLC-MS/MS. We report 16 new vectors for these toxins in the North Atlantic. There were differences in toxin contents among species, but no significant geographical or seasonal patterns were found. Our results suggest that legislation should be adjusted to extend the monitoring of marine toxins to a wider range of species besides edible bivalves.

  11. Cost-effectiveness of extracorporeal shock wave lithotripsy in a poor resource setting: The Okada, Nigeria experience

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    Kenneth C Eze

    2016-01-01

    Full Text Available Background: The first extracorporeal shock wave lithotripsy (ESWL used in Nigeria was at Igbinedion Hospital and Medical Research Centre (IHMRC, Okada in 1992 and it functioned for 6 consecutive years. The objectives of this study were to analyze the cost-effectiveness of the procedure and highlight the associated factors that led to its failure. Methods: A retrospective study of medical records and publications associated with the use of ESWL at IHMRC, Okada, for the period of 1992 to 1998. The study was conducted between January 2003 and November 2008. Unclassified authentic information relating to the use of ESWL and treatment of upper urinary tract stones was obtained from the IHMRC Okada and some government hospitals on hospital bills. Relevant documents in public domains related to the national and international wages and emoluments of medical workers and socioeconomic development of Nigeria within the time the ESWL functioned were studied. Result: A total of 32 patients were treated with 51 treatment sessions which is an average of nine patients per year and an average of two treatment sessions per patient were involved. The reasons for the low patronage were the extremely low stone formation rate of Nigerians, poverty, and out-of-pocket payment system. In addition, each treatment session of ESWL at Okada cost an average of $681.8 compared to $227.3 for open nephrolithotomy in a nearby high profile teaching hospital. The IHMRC, Okada, paid an average annual salary of ₦180,000 ($8,181.8 for each medical consultant compared to ₦120,000 ($5,454.5 paid by federal teaching hospitals in Nigeria within the period. Expatriate consultant doctors from Europe and USA who initially manned the lithotriptor at IHMRC, Okada, were paid much higher salaries. Average annual income of $5,909 for each of the 6 years amounting to a total of $34,771.7 for the six years was realized which could not maintain staff salaries in the hospital leading to staff

  12. Assessment of okadaic acid effects on cytotoxicity, DNA damage and DNA repair in human cells.

    Science.gov (United States)

    Valdiglesias, Vanessa; Méndez, Josefina; Pásaro, Eduardo; Cemeli, Eduardo; Anderson, Diana; Laffon, Blanca

    2010-07-07

    Okadaic acid (OA) is a phycotoxin produced by several types of dinoflagellates causing diarrheic shellfish poisoning (DSP) in humans. Symptoms induced by DSP toxins are mainly gastrointestinal, but the intoxication does not appear to be fatal. Despite this, this toxin presents a potential threat to human health even at concentrations too low to induce acute toxicity, since previous animal studies have shown that OA has very potent tumour promoting activity. However, its concrete action mechanism has not been described yet and the results reported with regard to OA cytotoxicity and genotoxicity are often contradictory. In the present study, the genotoxic and cytotoxic effects of OA on three different types of human cells (peripheral blood leukocytes, HepG2 hepatoma cells, and SHSY5Y neuroblastoma cells) were evaluated. Cells were treated with a range of OA concentrations in the presence and absence of S9 fraction, and MTT test and Comet assay were performed in order to evaluate cytotoxicity and genotoxicity, respectively. The possible effects of OA on DNA repair were also studied by means of the DNA repair competence assay, using bleomycin as DNA damage inductor. Treatment with OA in absence of S9 fraction induced not statistically significant decrease in cell viability and significant increase in DNA damage in all cell types at the highest concentrations investigated. However, only SHSY5Y cells showed OA induced genotoxic and cytotoxic effects in presence of S9 fraction. Furthermore, we found that OA can induce modulations in DNA repair processes when exposure was performed prior to BLM treatment, in co-exposure, or during the subsequent DNA repair process. Copyright 2010 Elsevier B.V. All rights reserved.

  13. Neuroprotective effect of curcumin on okadaic acid induced memory impairment in mice.

    Science.gov (United States)

    Rajasekar, N; Dwivedi, Subhash; Tota, Santosh Kumar; Kamat, Pradeep Kumar; Hanif, Kashif; Nath, Chandishwar; Shukla, Rakesh

    2013-09-05

    Okadaic acid (OKA) has been observed to cause memory impairment in human subjects having seafood contaminated with dinoflagellate (Helicondria okadai). OKA induces tau hyperphosphorylation and oxidative stress leading to memory impairment as our previous study has shown. Curcumin a natural antioxidant has demonstrated neuroprotection in various models of neurodegeneration. However, the effect of curcumin has not been explored in OKA induced memory impairment. Therefore, present study evaluated the effect of curcumin on OKA (100ng, intracerebrally) induced memory impairment in male Swiss albino mice as evaluated in Morris water maze (MWM) and passive avoidance tests (PAT). OKA administration resulted in memory impairment with a decreased cerebral blood flow (CBF) (measured by laser doppler flowmetry), ATP level and increased mitochondrial (Ca(2+))i, neuroinflammation (increased TNF-α, IL-1β, COX-2 and GFAP), oxidative-nitrosative stress, increased Caspase-9 and cholinergic dysfunction (decreased AChE activity/expression and α7 nicotinic acetylcholine receptor expression) in cerebral cortex and hippocampus of mice brain. Oral administration of curcumin (50mg/kg) for 13 days significantly improved memory function in both MWM and PAT along with brain energy metabolism, CBF and cholinergic function. It decreased mitochondrial (Ca(2+))i, and ameliorated neuroinflammation and oxidative-nitrostative stress in different brain regions of OKA treated mice. Curcumin also inhibited astrocyte activation as evidenced by decreased GFAP expression. This neuroprotective effect of curcumin is due to its potent anti-oxidant action thus confirming previous studies. Therefore, use of curcumin should be encouraged in people consuming sea food (contaminated with dinoflagellates) to prevent cognitive impairment.

  14. Generation of Internal-Image Functional Aptamers of Okadaic Acid via Magnetic-Bead SELEX

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    Chao Lin

    2015-12-01

    Full Text Available Okadaic acid (OA is produced by Dinophysis and Prorocentrum dinoflagellates and primarily accumulates in bivalves, and this toxin has harmful effects on consumers and operators. In this work, we first report the use of aptamers as novel non-toxic probes capable of binding to a monoclonal antibody against OA (OA-mAb. Aptamers that mimic the OA toxin with high affinity and selectivity were generated by the magnetic bead-assisted systematic evolution of ligands by exponential enrichment (SELEX strategy. After 12 selection rounds, cloning, sequencing and enzyme-linked immunosorbent assay (ELISA analysis, four candidate aptamers (O24, O31, O39, O40 were selected that showed high affinity and specificity for OA-mAb. The affinity constants of O24, O31, O39 and O40 were 8.3 × 108 M−1, 1.47 × 109 M−1, 1.23 × 109 M−1 and 1.05 × 109 M−1, respectively. Indirect competitive ELISA was employed to determine the internal-image function of the aptamers. The results reveal that O31 has a similar competitive function as free OA toxin, whereas the other three aptamers did not bear the necessary internal-image function. Based on the derivation of the curvilinear equation for OA/O31, the equation that defined the relationship between the OA toxin content and O31 was Y = 2.185X − 1.78. The IC50 of O31 was 3.39 ng·mL−1, which was close to the value predicted by the OA ELISA (IC50 = 4.4 ng·mL−1; the IC10 was 0.33 ng·mL−1. The above data provides strong evidence that internal-image functional aptamers could be applicable as novel probes in a non-toxic assay.

  15. Generation of Internal-Image Functional Aptamers of Okadaic Acid via Magnetic-Bead SELEX.

    Science.gov (United States)

    Lin, Chao; Liu, Zeng-Shan; Wang, Dong-Xu; Li, Lin; Hu, Pan; Gong, Sheng; Li, Yan-Song; Cui, Cheng; Wu, Zong-Cheng; Gao, Yang; Zhou, Yu; Ren, Hong-Lin; Lu, Shi-Ying

    2015-12-17

    Okadaic acid (OA) is produced by Dinophysis and Prorocentrum dinoflagellates and primarily accumulates in bivalves, and this toxin has harmful effects on consumers and operators. In this work, we first report the use of aptamers as novel non-toxic probes capable of binding to a monoclonal antibody against OA (OA-mAb). Aptamers that mimic the OA toxin with high affinity and selectivity were generated by the magnetic bead-assisted systematic evolution of ligands by exponential enrichment (SELEX) strategy. After 12 selection rounds, cloning, sequencing and enzyme-linked immunosorbent assay (ELISA) analysis, four candidate aptamers (O24, O31, O39, O40) were selected that showed high affinity and specificity for OA-mAb. The affinity constants of O24, O31, O39 and O40 were 8.3 × 10⁸ M(-1), 1.47 × 10⁸ M(-1), 1.23 × 10⁸ M(-1) and 1.05 × 10⁸ M(-1), respectively. Indirect competitive ELISA was employed to determine the internal-image function of the aptamers. The results reveal that O31 has a similar competitive function as free OA toxin, whereas the other three aptamers did not bear the necessary internal-image function. Based on the derivation of the curvilinear equation for OA/O31, the equation that defined the relationship between the OA toxin content and O31 was Y = 2.185X - 1.78. The IC50 of O31 was 3.39 ng·mL(-1), which was close to the value predicted by the OA ELISA (IC50 = 4.4 ng·mL(-1)); the IC10 was 0.33 ng·mL(-1). The above data provides strong evidence that internal-image functional aptamers could be applicable as novel probes in a non-toxic assay.

  16. Antibody-based donor-acceptor spatial reconfiguration in decorated lanthanide-doped nanoparticle colloids for the quantification of okadaic acid biotoxin.

    Science.gov (United States)

    Stipić, Filip; Burić, Petra; Jakšić, Željko; Pletikapić, Galja; Dutour Sikirić, Maja; Zgrablić, Goran; Frkanec, Leo; Lyons, Daniel M

    2015-11-01

    With the increasing movement away from the mouse bioassay for the detection of toxins in commercially harvested shellfish, there is a growing demand for the development of new and potentially field-deployable tests in its place. In this direction we report the development of a simple and sensitive nanoparticle-based luminescence technique for the detection of the marine biotoxin okadaic acid. Photoluminescent lanthanide nanoparticles were conjugated with fluorophore-labelled anti-okadaic acid antibodies which, upon binding to okadaic acid, gave rise to luminescence resonance energy transfer from the nanoparticle to the organic fluorophore dye deriving from a reduction in distance between the two. The intensity ratio of the fluorophore: nanoparticle emission peaks was found to correlate with okadaic acid concentration, and the sensor showed a linear response in the 0.37-3.97 μM okadaic acid range with a limit of detection of 0.25 μM. This work may have important implications for the development of new, cheap, and versatile biosensors for a range of biomolecules and that are sufficiently simple to be applied in the field or at point-of-care.

  17. New Invertebrate Vectors of Okadaic Acid from the North Atlantic Waters--Portugal (Azores and Madeira) and Morocco.

    Science.gov (United States)

    Silva, Marisa; Rodriguez, Inés; Barreiro, Aldo; Kaufmann, Manfred; Isabel Neto, Ana; Hassouani, Meryem; Sabour, Brahim; Alfonso, Amparo; Botana, Luis M; Vasconcelos, Vitor

    2015-12-08

    Okadaic acid and its analogues are potent phosphatase inhibitors that cause Diarrheic Shellfish Poisoning (DSP) through the ingestion of contaminated shellfish by humans. This group of toxins is transmitted worldwide but the number of poisoning incidents has declined over the last 20 years due to legislation and monitoring programs that were implemented for bivalves. In the summer of 2012 and 2013, we collected a total of 101 samples of 22 different species that were made up of benthic and subtidal organisms such echinoderms, crustaceans, bivalves and gastropods from Madeira, São Miguel Island (Azores archipelago) and the northwestern coast of Morocco. The samples were analyzed by UPLC-MS/MS. Our main objective was to detect new vectors for these biotoxins. We can report nine new vectors for these toxins in the North Atlantic: Astropecten aranciacus, Arbacia lixula, Echinaster sepositus, Holothuria sanctori, Ophidiaster ophidianus, Onchidella celtica, Aplysia depilans, Patella spp., and Stramonita haemostoma. Differences in toxin contents among the species were found. Even though low concentrations were detected, the levels of toxins that were present, especially in edible species, indicate the importance of these types of studies. Routine monitoring should be extended to comprise a wider number of vectors other than for bivalves of okadaic acid and its analogues.

  18. New Invertebrate Vectors of Okadaic Acid from the North Atlantic Waters—Portugal (Azores and Madeira and Morocco

    Directory of Open Access Journals (Sweden)

    Marisa Silva

    2015-12-01

    Full Text Available Okadaic acid and its analogues are potent phosphatase inhibitors that cause Diarrheic Shellfish Poisoning (DSP through the ingestion of contaminated shellfish by humans. This group of toxins is transmitted worldwide but the number of poisoning incidents has declined over the last 20 years due to legislation and monitoring programs that were implemented for bivalves. In the summer of 2012 and 2013, we collected a total of 101 samples of 22 different species that were made up of benthic and subtidal organisms such echinoderms, crustaceans, bivalves and gastropods from Madeira, São Miguel Island (Azores archipelago and the northwestern coast of Morocco. The samples were analyzed by UPLC-MS/MS. Our main objective was to detect new vectors for these biotoxins. We can report nine new vectors for these toxins in the North Atlantic: Astropecten aranciacus, Arbacia lixula, Echinaster sepositus, Holothuria sanctori, Ophidiaster ophidianus, Onchidella celtica, Aplysia depilans, Patella spp., and Stramonita haemostoma. Differences in toxin contents among the species were found. Even though low concentrations were detected, the levels of toxins that were present, especially in edible species, indicate the importance of these types of studies. Routine monitoring should be extended to comprise a wider number of vectors other than for bivalves of okadaic acid and its analogues.

  19. New Invertebrate Vectors of Okadaic Acid from the North Atlantic Waters—Portugal (Azores and Madeira) and Morocco

    Science.gov (United States)

    Silva, Marisa; Rodriguez, Inés; Barreiro, Aldo; Kaufmann, Manfred; Neto, Ana Isabel; Hassouani, Meryem; Sabour, Brahim; Alfonso, Amparo; Botana, Luis M.; Vasconcelos, Vitor

    2015-01-01

    Okadaic acid and its analogues are potent phosphatase inhibitors that cause Diarrheic Shellfish Poisoning (DSP) through the ingestion of contaminated shellfish by humans. This group of toxins is transmitted worldwide but the number of poisoning incidents has declined over the last 20 years due to legislation and monitoring programs that were implemented for bivalves. In the summer of 2012 and 2013, we collected a total of 101 samples of 22 different species that were made up of benthic and subtidal organisms such echinoderms, crustaceans, bivalves and gastropods from Madeira, São Miguel Island (Azores archipelago) and the northwestern coast of Morocco. The samples were analyzed by UPLC-MS/MS. Our main objective was to detect new vectors for these biotoxins. We can report nine new vectors for these toxins in the North Atlantic: Astropecten aranciacus, Arbacia lixula, Echinaster sepositus, Holothuria sanctori, Ophidiaster ophidianus, Onchidella celtica, Aplysia depilans, Patella spp., and Stramonita haemostoma. Differences in toxin contents among the species were found. Even though low concentrations were detected, the levels of toxins that were present, especially in edible species, indicate the importance of these types of studies. Routine monitoring should be extended to comprise a wider number of vectors other than for bivalves of okadaic acid and its analogues. PMID:26670254

  20. Differentiation, early response gene expression, and apoptosis induction in human breast tumor cells by Okadaic Acid and related inhibitors of protein phosphatases 1 and 2A. Okadaic acid effects on human breast tumor cells

    Energy Technology Data Exchange (ETDEWEB)

    Kiguchi, K.; Giometti, C.; Chubb, C.H.; Huberman, E. [Argonne National Lab., IL (United States); Fujiki, H. [National Cancer Center Research Institute, Tokyo (Japan)

    1992-08-20

    Okadaic acid (OA), a tumor promoter and an inhibitor of protein phosphatases (PPH) 1 and 2A, was tested for its ability to induce events associated with differentiation and apoptosis induction in the human MCF-7, AU-565, and MB-231 breast tumor cells. Differentiation in these cells was characterized by inhibition of cell multiplication, reactivity with monoclonal antibodies to {alpha}-lactalbumin and {beta}-casein, and the appearance of large lipid droplets; apoptosis was characterized by the appearance of cells with segmented and fragmented nuclei. In the MCF-7 cell line, OA at nanomolar concentrations elicited within 5 min an increase in the phosphorylation of a set of cellular proteins, within hours expression of the early response genes, junB, c-jun, and c-fos and within days manifestation of differentiation and apoptosis markers. Differentiation and apoptosis were also induced by dinophysistoxin-1 and calyculin A, two other tumor promoters and inhibitors of PPH 1 and 2A, but not by OA tetramethyl ether, an inactive OA derivative, or microcystin LR, a PPH 1 and 2A inhibitor that penetrates epithelial cells poorly. OA induced both differentiation and apoptosis in MB-231 cells and MCF-7, but only differentiation in AU-565 cells. Phorbol 12-myristate 13-acetate (PMA), a tumor promoter that is not an inhibitor of PPH 1 and 2A but rather an activator of protein kinase C, also induced within minutes the phosphorylation of proteins, within hours the expression of early response genes, and within days differentiation, but not apoptosis; yet PMA was able to attenuate apoptosis induced by the okadaic acid class of tumor promoters. These results indicate that OA and related agents can induce processes that result in tumor breast cell differentiation and apoptosis, and this induction is associated with their ability to inhibit PPH 1 and 2A. Yet apoptosis is not necessarily required for differentiation induction by these agents.

  1. LC-MS/MS analysis of diarrhetic shellfish poisoning (DSP) toxins, okadaic acid and dinophysistoxin analogues, and other lipophilic toxins.

    Science.gov (United States)

    Suzuki, Toshiyuki; Quilliam, Michael A

    2011-01-01

    Diarrhetic shellfish poisoning (DSP) is a severe gastrointestinal illness caused by consumption of shellfish contaminated with DSP toxins that are originally produced by toxic dinoflagellates. Based on their structures, DSP toxins were initially classified into three groups, okadaic acid (OA)/dinophysistoxin (DTX) analogues, pectenotoxins (PTXs), and yessotoxins (YTXs). Because PTXs and YTXs have been subsequently shown to have no diarrhetic activities, PTXs and YTXs have recently been eliminated from the definition of DSP toxins. Mouse bioassay (MBA), which is the official testing method of DSP in Japan and many countries, also detects PTXs and YTXs, and thus alternative testing methods detecting only OA/DTX analogues are required in DSP monitoring. Electrospray ionization (ESI) liquid chromatography-mass spectrometry (LC-MS) is a very powerful tool for the detection, identification and quantification of DSP and other lipophilic toxins. In the present review, application of ESI LC-MS techniques to the analysis of each toxin group is described.

  2. Development of a novel immunobiosensor method for the rapid detection of okadaic acid contamination in shellfish extracts.

    Science.gov (United States)

    Llamas, Nuria M; Stewart, Linda; Fodey, Terry; Higgins, H Cowan; Velasco, María Luisa R; Botana, Luis M; Elliott, Christopher T

    2007-09-01

    The mouse bioassay is the methodology that is most widely used to detect okadaic acid (OA) in shellfish samples. This is one of the best-known toxins, and it belongs to the family of marine biotoxins referred to as the diarrhetic shellfish poisons (DSP). Due to animal welfare concerns, alternative methods of toxin detection are being sought. A rapid and specific biosensor immunoassay method was developed and validated for the detection of OA. An optical sensor instrument based on the surface plasmon resonance (SPR) phenomenon was utilised. A polyclonal antibody to OA was raised against OA-bovine thyroglobulin conjugate and OA-N-hydroxy succinimide ester was immobilised onto an amine sensor chip surface. The assay parameters selected for the analysis of the samples were: antibody dilution, 1/750; ratio of antibody to standard, 1:1; volume of sample injected, 25 microl min(-1); flow rate, 25 microl min(-1). An assay action limit of 126 ng g(-1) was established by analysing of 20 shellfish samples spiked with OA at the critical concentration of 160 ng g(-1), which is the action limit established by the European Union (EU). At this concentration of OA, the assay delivered coefficient of variations (CVs) of biosensor method were compared with the values obtained by LC-MS in contaminated shellfish samples, the correlation between the two analytical methods was found to be highly satisfactory (r(2) = 0.991).

  3. Development of a Novel and Robust Pharmacological Model of Okadaic Acid-induced Alzheimer's Disease in Zebrafish.

    Science.gov (United States)

    Nada, Shadia E; Williams, Frederick E; Shah, Zahoor A

    2016-01-01

    Alzheimer's disease (AD) is the leading neurodegenerative disorder affecting the world's elderly population. Most experimental models of AD are transgenic or pharmacological in nature, and do not simulate the entire pathophysiology. In the present study, we developed a pharmacologically induced AD using the zebrafish, a species that can recapitulate most of the phenotypes of the disease. The pharmacological agent being used, okadaic acid (OKA) has also been utilized to study AD in other species. In this model, the immunohistochemistry of phosphorylated glycogen synthase-3α/β, Aβ, p-tau, tau protein, and senile plaque formation in zebrafish brain were all significantly increased with increasing exposure to OKA. These represent the majority of the histological hallmarks of AD pathophysiology. The observed changes were also accompanied by learning and memory deficits which are also important components in AD pathophysiology. Zebrafish disease models are gaining popularity mostly due to their economic cost and relevance to human disease pathophysiology. Current pharmacological methods of inducing AD in zebrafish are not adequately developed and do not represent all the features of the disease. OKA-induced AD in zebrafish can become a cost efficient model to study drug discovery for AD. It may also be used to unravel the molecular mechanisms underlying the complex pathophysiology that leads to AD using relatively economical species.

  4. Mechanisms of the spatial memory deficits induced by injection of okadaic acid into the Meynert nucleus basalis of rats

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    We previously reported that the injection of okadaic acid(OA)into the Meynert nucleus basalis of rats induced spatial memory deficits.The present study was designed to further explore the underlying mechanisms.We found that the level of acetylcholine(Ach)in the hippocampus significantly decreased 24 h after injection of OA into the Meynert nucleus basalis of rats.Simultaneously,spatial memory deficit,PP-2A inhibition and tau hyperphosphorylation at Ser-198/Ser-199/Ser-202 (Tau-1 epitope)and Ser-396/Ser-404(PHF-1 epitope)were observed.With the restoration of hippocampus Ach to normal levels at 48 and 72 h after the injection,the spatial memory deficits,PP-2A inhibition and tau hyperphosphorylation were reversed.It is suggested that injection of OA into the Meynert nucleus basalis of rats may impair the hippocampus-dependent spatial memory through damaging the cholinergic projection between the Meynert nucleus basalis and the hippocampus and the selective inhibition of PP-2A and tau hyperphosphorylation may be at least part of the underlying mechanisms.

  5. Histone Modification Is Involved in Okadaic Acid (OA Induced DNA Damage Response and G2-M Transition Arrest in Maize.

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    Hao Zhang

    Full Text Available Histone modifications are involved in regulation of chromatin structure. To investigate the relationship between chromatin modification and cell cycle regulation during plant cell proliferation, Okadaic acid (OA, a specific inhibitor of serine/threonine protein phosphatase, was applied in this study. The results showed that OA caused the cell cycle arrest at preprophase, leading to seedling growth inhibition. Western blotting assay revealed that the spatial distribution of phosphorylation of Ser10 histone H3 tails (H3S10ph signals was altered under OA treatment. Reactive oxygen species (ROS was found to be at higher levels and TdT-mediated dUTP nick end labeling (TUNEL assay displayed DNA breaks happened at the chromatin after treatment with OA, companied with an increase in the acetylation of histone H4 at lysine 5 (H4K5ac level. From these observations, we speculated that the alteration of the spatial distribution of H3S10ph and the level of H4K5ac was involved in the procedure that OA induced DNA breaks and G2-M arrested by the accumulation of ROS, and that the histone H3S10ph and H4K5ac might facilitate DNA repair by their association with the chromatin decondensation.

  6. Comparative Analysis of the Cytotoxic Effects of Okadaic Acid-Group Toxins on Human Intestinal Cell Lines

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    Pierre-Jean Ferron

    2014-08-01

    Full Text Available The phycotoxin, okadaic acid (OA and dinophysistoxin 1 and 2 (DTX-1 and -2 are protein phosphatase PP2A and PP1 inhibitors involved in diarrhetic shellfish poisoning (DSP. Data on the toxicity of the OA-group toxins show some differences with respect to the in vivo acute toxicity between the toxin members. In order to investigate whether OA and congeners DTX-1 and -2 may induce different mechanisms of action during acute toxicity on the human intestine, we compared their toxicological effects in two in vitro intestinal cell models: the colorectal adenocarcinoma cell line, Caco-2, and the intestinal muco-secreting cell line, HT29-MTX. Using a high content analysis approach, we evaluated various cytotoxicity parameters, including apoptosis (caspase-3 activation, DNA damage (phosphorylation of histone H2AX, inflammation (translocation of NF-κB and cell proliferation (Ki-67 production. Investigation of the kinetics of the cellular responses demonstrated that the three toxins induced a pro-inflammatory response followed by cell cycle disruption in both cell lines, leading to apoptosis. Our results demonstrate that the three toxins induce similar effects, as no major differences in the cytotoxic responses could be detected. However DTX-1 induced cytotoxic effects at five-fold lower concentrations than for OA and DTX-2.

  7. Single Laboratory Validation of A Ready-to-Use Phosphatase Inhibition Assay for Detection of Okadaic Acid Toxins

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    Luis Mata

    2012-04-01

    Full Text Available A phosphatase inhibition assay for detection of okadaic acid (OA toxins in shellfish, OkaTest, was single laboratory validated according to international recognized guidelines (AOAC, EURACHEM. Special emphasis was placed on the ruggedness of the method and stability of the components. All reagents were stable for more than 6 months and the method was highly robust under normal laboratory conditions. The limit of detection and quantification were 44 and 56 µg/kg, respectively; both below the European legal limit of 160 µg/kg. The repeatability was evaluated with 2 naturally contaminated samples. The relative standard deviation (RSD calculated was 1.4% at a level of 276 µg/kg and 3.9% at 124 µg/kg. Intermediate precision was estimated by testing 10 different samples (mussel and scallop on three different days and ranged between 2.4 and 9.5%. The IC50 values of the phosphatase used in this assay were determined for OA (1.2 nM, DTX-1 (1.6 nM and DTX-2 (1.2 nM. The accuracy of the method was estimated by recovery testing for OA (mussel, 78–101%; king scallop, 98–114%, DTX-1 (king scallop, 79–102% and DTX-2 (king scallop, 93%. Finally, the method was qualitatively compared to the mouse bioassay and LC-MS/MS.

  8. First detection and seasonal variation of lipophilic toxins okadaic acid, dinophysistoxin-1, and yessotoxin in Korean gastropods.

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    Lee, Ka Jeong; Mok, Jong Soo; Song, Ki Cheol; Yu, Hongsik; Lee, Doo Seog; Jung, Jee Hyung; Kim, Ji Hoe

    2012-11-01

    Okadaic acid (OA), dinophysistoxin-1 (DTX1), pectenotoxin-2, and yessotoxin (YTX) are classes of lipophilic toxins found in marine animals. OA and DTX1 accumulation causes diarrhetic shellfish poisoning, a worldwide public health problem. Diarrhetic shellfish poisoning has not previously been reported in gastropods, which are widely consumed in Korea. Seasonal variation in marine lipophilic toxins in gastropods was investigated using liquid chromatography-tandem mass spectrometry. Eighty specimens of Neptunea cumingii, 65 specimens of Rapana venosa, and 95 specimens of Batillus cornutus were collected at the Tongyeong fish market on the southern coast of Korea between May 2009 and December 2010. OA, DTX1, and YTX were detected in meat and digestive glands in all gastropod species studied. Pectenotoxin-2 was not found in any sample tested. Lipophilic toxins were detected in the digestive glands of gastropods; no lipophilic toxin was detected in the salivary glands of the carnivorous gastropods, N. cumingii and R. venosa. The highest concentrations of OA (21.5 ng/g) and DTX1 (8.4 ng/g) were detected in the digestive glands of R. venosa, and the maximum concentration of YTX (13.7 ng/g) was found in the digestive glands of N. cumingii. The maximum toxicities in gastropod tissues were lower than the European standard for acceptable levels. The concentrations of lipophilic toxins in carnivorous gastropods showed a high degree of seasonal variation; lipophilic toxins in carnivorous gastropods were found predominantly in spring and summer. This is the first report of the occurrence of lipophilic toxins in Korean gastropods.

  9. Sulforaphane Ameliorates Okadaic Acid-Induced Memory Impairment in Rats by Activating the Nrf2/HO-1 Antioxidant Pathway.

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    Dwivedi, Subhash; Rajasekar, N; Hanif, Kashif; Nath, Chandishwar; Shukla, Rakesh

    2016-10-01

    Okadaic acid (OKA) causes memory impairment and attenuates nuclear factor erythroid 2-related factor 2 (Nrf2) along with oxidative stress and neuroinflammation in rats. Sulforaphane (dietary isothiocyanate compound), an activator of Nrf2 signaling, exhibits neuroprotective effects. However, the protective effect of sulforaphane in OKA-induced neurotoxicity remains uninvestigated. Therefore, in the present study, the role of sulforaphane in OKA-induced memory impairment in rats was explored. A significant increased Nrf2 expression in the hippocampus and cerebral cortex was observed in trained (Morris water maze) rats, and a significant decreased Nrf2 expression in memory-impaired (OKA, 200 ng icv) rats indicated its involvement in memory function. Sulforaphane administration (5 and 10 mg/kg, ip, days 1 and 2) ameliorates OKA-induced memory impairment in rats. The treatment also restored Nrf2 and its downstream antioxidant protein expression (GCLC, HO-1) and attenuated oxidative stress (ROS, nitrite, GSH), neuroinflammation (NF-κB, TNF-α, IL-10), and neuronal apoptosis in the cerebral cortex and hippocampus of OKA-treated rats. Further, to determine whether modulation of Nrf2 signaling is responsible for the protective effect of sulforaphane, in vitro, Nrf2 siRNA and its downstream HO-1 inhibition studies were carried out in a rat astrocytoma cell line (C6). The protective effects of sulforaphane were abolished with Nrf2 siRNA and HO-1 inhibition in astrocytes. The results suggest that Nrf2-dependent activation of cellular antioxidant machinery results in sulforaphane-mediated protection against OKA-induced memory impairment in rats. Graphical Abstract ᅟ.

  10. Does the marine biotoxin okadaic acid cause DNA fragmentation in the blue mussel and the pacific oyster?

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    McCarthy, Moira; O'Halloran, John; O'Brien, Nora M; van Pelt, Frank F N A M

    2014-10-01

    Two bivalve species of global economic importance: the blue mussel, Mytilus edulis and the pacific oyster, Crassostrea gigas were exposed in vivo, to the diarrhoetic shellfish toxin okadaic acid (OA), and impacts on DNA fragmentation were measured. Shellfish were exposed using two different regimes, the first was a single (24 h) exposure of 2.5 nM OA (∼0.1 μg/shellfish) and algal feed at the beginning of the trial (T0), after which shellfish were only fed algae. The second was daily exposure of shellfish to two different concentrations of OA mixed with the algal feed over 7 days; 1.2 nM OA (∼0.05 μg OA/shellfish/day) and 50 nM OA (∼2 μg OA/shellfish/day). Haemolymph and hepatopancreas cells were extracted following 1, 3 and 7 days exposure. Cell viability was measured using the trypan blue exclusion assay and remained above 85% for both cell types. DNA fragmentation was examined using the single-cell gel electrophoresis (comet) assay. A significant increase in DNA fragmentation was observed in the two cell types from both species relative to the controls. This increase was greater in the pacific oyster at the higher toxin concentration. However, there was no difference in the proportion of damage measured between the two cell types, and a classic dose response was not observed, increasing toxin concentration did not correspond to increased DNA fragmentation. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Identification of differentially expressed genes in SHSY5Y cells exposed to okadaic acid by suppression subtractive hybridization

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    Valdiglesias Vanessa

    2012-01-01

    Full Text Available Abstract Background Okadaic acid (OA, a toxin produced by several dinoflagellate species is responsible for frequent food poisonings associated to shellfish consumption. Although several studies have documented the OA effects on different processes such as cell transformation, apoptosis, DNA repair or embryogenesis, the molecular mechanistic basis for these and other effects is not completely understood and the number of controversial data on OA is increasing in the literature. Results In this study, we used suppression subtractive hybridization in SHSY5Y cells to identify genes that are differentially expressed after OA exposure for different times (3, 24 and 48 h. A total of 247 subtracted clones which shared high homology with known genes were isolated. Among these, 5 specific genes associated with cytoskeleton and neurotransmission processes (NEFM, TUBB, SEPT7, SYT4 and NPY were selected to confirm their expression levels by real-time PCR. Significant down-regulation of these genes was obtained at the short term (3 and 24 h OA exposure, excepting for NEFM, but their expression was similar to the controls at 48 h. Conclusions From all the obtained genes, 114 genes were up-regulated and 133 were down-regulated. Based on the NCBI GenBank and Gene Ontology databases, most of these genes are involved in relevant cell functions such as metabolism, transport, translation, signal transduction and cell cycle. After quantitative PCR analysis, the observed underexpression of the selected genes could underlie the previously reported OA-induced cytoskeleton disruption, neurotransmission alterations and in vivo neurotoxic effects. The basal expression levels obtained at 48 h suggested that surviving cells were able to recover from OA-caused gene expression alterations.

  12. Unbiased high-throughput characterization of mussel transcriptomic responses to sublethal concentrations of the biotoxin okadaic acid

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    Victoria Suarez-Ulloa

    2015-11-01

    Full Text Available Background. Harmful Algal Blooms (HABs responsible for Diarrhetic Shellfish Poisoning (DSP represent a major threat for human consumers of shellfish. The biotoxin Okadaic Acid (OA, a well-known phosphatase inhibitor and tumor promoter, is the primary cause of acute DSP intoxications. Although several studies have described the molecular effects of high OA concentrations on sentinel organisms (e.g., bivalve molluscs, the effect of prolonged exposures to low (sublethal OA concentrations is still unknown. In order to fill this gap, this work combines Next-Generation sequencing and custom-made microarray technologies to develop an unbiased characterization of the transcriptomic response of mussels during early stages of a DSP bloom.Methods. Mussel specimens were exposed to a HAB episode simulating an early stage DSP bloom (200 cells/L of the dinoflagellate Prorocentrum lima for 24 h. The unbiased characterization of the transcriptomic responses triggered by OA was carried out using two complementary methods of cDNA library preparation: normalized and Suppression Subtractive Hybridization (SSH. Libraries were sequenced and read datasets were mapped to Gene Ontology and KEGG databases. A custom-made oligonucleotide microarray was developed based on these data, completing the expression analysis of digestive gland and gill tissues.Results. Our findings show that exposure to sublethal concentrations of OA is enough to induce gene expression modifications in the mussel Mytilus. Transcriptomic analyses revealed an increase in proteasomal activity, molecular transport, cell cycle regulation, energy production and immune activity in mussels. Oppositely, a number of transcripts hypothesized to be responsive to OA (notably the Serine/Threonine phosphatases PP1 and PP2A failed to show substantial modifications. Both digestive gland and gill tissues responded similarly to OA, although expression modifications were more dramatic in the former, supporting the

  13. Simultaneous Effect of Temperature and Irradiance on Growth and Okadaic Acid Production from the Marine Dinoflagellate Prorocentrum belizeanum

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    Lorenzo López-Rosales

    2014-01-01

    Full Text Available Benthic marine dioflagellate microalgae belonging to the genus Prorocentrum are a major source of okadaic acid (OA, OA analogues and polyketides. However, dinoflagellates produce these valuable toxins and bioactives in tiny quantities, and they grow slowly compared to other commercially used microalgae. This hinders evaluation in possible large-scale applications. The careful selection of producer species is therefore crucial for success in a hypothetical scale-up of culture, as are appropriate environmental conditions for optimal growth. A clone of the marine toxic dinoflagellate P. belizeanum was studied in vitro to evaluate its capacities to grow and produce OA as an indicator of general polyketide toxin production under the simultaneous influence of temperature (T and irradiance (I0. Three temperatures and four irradiance levels were tested (18, 25 and 28 °C; 20, 40, 80 and 120 µE·m−2·s−1, and the response variables measured were concentration of cells, maximum photochemical yield of photosystem II (PSII, pigments and OA. Experiments were conducted in T-flasks, since their parallelepipedal geometry proved ideal to ensure optically thin cultures, which are essential for reliable modeling of growth-irradiance curves. The net maximum specific growth rate (µm was 0.204 day−1 at 25 °C and 40 µE·m−2·s−1. Photo-inhibition was observed at I0 > 40 μEm−2s−1, leading to culture death at 120 µE·m−2·s−1 and 28 °C. Cells at I0 ≥ 80 µE·m−2·s−1 were photoinhibited irrespective of the temperature assayed. A mechanistic model for µm-I0 curves and another empirical model for relating µm-T satisfactorily interpreted the growth kinetics obtained. ANOVA for responses of PSII maximum photochemical yield and pigment profile has demonstrated that P. belizeanum is extremely light sensitive. The pool of photoprotective pigments (diadinoxanthin and dinoxanthin and peridinin was not able to regulate the excessive light

  14. Evaluation of the Impact of Mild Steaming and Heat Treatment on the Concentration of Okadaic Acid, Dinophysistoxin-2 and Dinophysistoxin-3 in Mussels

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    Inés Rodríguez

    2016-06-01

    Full Text Available This study explores the effect of laboratory and industrial steaming on mussels with toxin concentrations above and below the legal limit. We used mild conditions for steaming, 100 °C for 5 min in industrial processing, and up to 20 min in small-scale laboratory steaming. Also, we studied the effect of heat on the toxin concentration of mussels obtained from two different locations and the effect of heat on the levels of dinophysistoxins 3 (DTX3 in both the mussel matrix and in pure form (7-O-palmitoyl okadaic ester and 7-O-palmytoleyl okadaic ester. The results show that the loss of water due to steaming was very small with a maximum of 9.5%, that the toxin content remained unchanged with no concentration effect or increase in toxicity, and that dinophysistoxins 3 was hydrolyzed or degraded to a certain extent under heat treatment. The use of liquid-certified matrix showed a 55% decrease of dinophysistoxins 3 after 10 min steaming, and a 50% reduction in total toxicity after treatment with an autoclave (121 °C for 20 min.

  15. Stereochemistry of Complex Marine Natural Products by Quantum Mechanical Calculations of NMR Chemical Shifts: Solvent and Conformational Effects on Okadaic Acid

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    Humberto J. Domínguez

    2014-01-01

    Full Text Available Marine organisms are an increasingly important source of novel metabolites, some of which have already inspired or become new drugs. In addition, many of these molecules show a high degree of novelty from a structural and/or pharmacological point of view. Structure determination is generally achieved by the use of a variety of spectroscopic methods, among which NMR (nuclear magnetic resonance plays a major role and determination of the stereochemical relationships within every new molecule is generally the most challenging part in structural determination. In this communication, we have chosen okadaic acid as a model compound to perform a computational chemistry study to predict 1H and 13C NMR chemical shifts. The effect of two different solvents and conformation on the ability of DFT (density functional theory calculations to predict the correct stereoisomer has been studied.

  16. Construction and application of gold-labeled immunology assay for the detection of okadaic acid%软海绵酸胶体金免疫检测法的建立与应用

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    蔡春尔; 柳俊秀; 胡乐琴; 贾睿; 汪卿; 李春霞; 何培民

    2012-01-01

    Objective To construct and apply gold-labeled immunology assay for the detection of okadaic acid. Methods Gold-labeled immunology testing technology for fast detecting okadaic acid was established and optimized by a series of procedures,inclu-ding purification of monoclonal antibody of okadaic acid, preparation of colloidal gold, label of monoclonalantibody, preparation of strip,simulated sample extraction andspikedrecoverydetection,followed by extraction and testing of exposed shellfish. Results 30 nm colloidal gold particles were used to mark the test strip, the concentration and coated amount of go Id-labeled monoclonal anti-body were 200 μg/mL and 2. 5 μL/cm, respectively, and the concentration of second antibody was 1. 0 mg/mL. The colloidal gold test strip detection in spiked shellfish and exposed shellfish were applied, with detection time of 3 - 5 minutes and detection limit of less than 25 ng/mL. Conclusion Go Id-labeled immunology assay for fast detecting okadaic acid was established, meeting the safe threshold of okadaic acid in shellfish food ruled by many countries and proving technical foundation for detection of okadaic acid in shellfish.%目的 建立并应用软海绵酸(OA)胶体金免疫层析检测法.方法 通过纯化抗OA单抗、制备胶体金、标记单抗、制备胶体金试剂条、样品模拟提取与加标回收检测、贝类染毒提取及检测,建立和优化金标免疫层析法.结果 选择30 nm胶体金颗粒用于单抗标记,金标单抗浓度为200 μg/mL,金标单抗包被量为2.5 μL/cm,二抗包被浓度为1.0 mg/mL,反应时间为3~5 min,对加标贝肉和染毒贝类的检测灵敏度为25 ng/mL.结论 建立了可用于OA检测的胶体金免疫层析检测法,满足规定的贝类OA含量安全阈值,为腹泻性贝毒检测与食品安全检验提供了新的技术方法.

  17. First report of diarrheic shellfish toxins in mollusks from Buenos Aires province (Argentina associated with dinophysis spp.: evidence of okadaic acid, dinophysistoxin-1 and their acylderivatives

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    Eugenia A Sar

    2012-06-01

    Full Text Available In January 2010, the toxin-producing dinoflagellates Dinophysis acuminata and D. caudata (10³ cells·l-1 were detected in Mar Azul during routine plankton monitoring in Buenos Aires Province coastal waters, Argentina. Wild clams Mesodesma mactroides and Donax hanleyanus from Mar Azul intertidal beach, which are part of the diet for local inhabitants and tourists, tested positive with the offcial lipophilic mouse bioassay. This paper focuses on the detection of Diarrhetic Shellfsh Poison (DSP toxins in these samples using a HPLC-FLD pre column derivatization procedure. The data showed that shellfish were contaminated with complex DSP toxin profiles composed of Okadaic Acid (OA, Dinophysistoxin-1 (DTX-1, Acyl-Dinophysistoxin-1 (Acyl-DTX-1 and Acyl-Okadaic Acid (Acyl-OA. The DSP toxins found in this study produce diarrhea symptoms consistent with those experienced by patients who had ingested cooked shellfish in January. This is the first report of Acyl-derivatives in South American Atlantic shellfish samples and of OA in Argentinean shellfish samples.Primer reporte de toxinas diarreicas de moluscos en bivalvos de la Provincia de Buenos Aires (Argentina asociado con Dinophysis spp.: evidencia de Ácido Okadaico, Dinophysistoxina-1 y sus acyl-derivados. En enero de 2010, los dinoflagelados productores de toxinas Dinophysis acuminata y D. caudata (10³ cells·l-1 fueron detectados en Mar Azul durante un monitoreo rutinario de fitoplancton realizado en aguas costeras de la Provincia de Buenos Aires, Argentina. Mesodesma mactroides (almeja amarilla y Donax hanleyanus (berberecho del intermareal de Mar Azul, que son parte de la dieta de los habitantes del lugar y de turistas, dieron resultado positivo para toxinas lipofílicas mediante bioensayo ratón. Este trabajo está focalizado en la detección de Toxinas Diarreicas de Moluscos (DSP en muestras colectadas durante el evento de toxicidad usando un HPLC-FLD con procedimiento de derivatizaci

  18. Quercetin Protects against Okadaic Acid-Induced Injury via MAPK and PI3K/Akt/GSK3β Signaling Pathways in HT22 Hippocampal Neurons

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    Li, Sheng; Zhou, Yue; Shen, Xiu-Yin; He, Feng; Xu, Jie; Wang, Hua-Qiao

    2016-01-01

    Increasing evidence shows that oxidative stress and the hyperphosphorylation of tau protein play essential roles in the progression of Alzheimer’s disease (AD). Quercetin is a major flavonoid that has anti-oxidant, anti-cancer and anti-inflammatory properties. We investigated the neuroprotective effects of quercetin to HT22 cells (a cell line from mouse hippocampal neurons). We found that Okadaic acid (OA) induced the hyperphosphorylation of tau protein at Ser199, Ser396, Thr205, and Thr231 and produced oxidative stress to the HT22 cells. The oxidative stress suppressed the cell viability and decreased the levels of lactate dehydrogenase (LDH), superoxide dismutase (SOD), mitochondria membrane potential (MMP) and Glutathione peroxidase (GSH-Px). It up-regulated malondialdehyde (MDA) production and intracellular reactive oxygen species (ROS). In addition, phosphoinositide 3 kinase/protein kinase B/Glycogen synthase kinase3β (PI3K/Akt/GSK3β) and mitogen activated protein kinase (MAPK) were also involved in this process. We found that pre-treatment with quercetin can inhibited OA-induced the hyperphosphorylation of tau protein and oxidative stress. Moreover, pre-treatment with quercetin not only inhibited OA-induced apoptosis via the reduction of Bax, and up-regulation of cleaved caspase 3, but also via the inhibition of PI3K/Akt/GSK3β, MAPKs and activation of NF-κB p65. Our findings suggest the therapeutic potential of quercetin to treat AD. PMID:27050422

  19. Quercetin Protects against Okadaic Acid-Induced Injury via MAPK and PI3K/Akt/GSK3β Signaling Pathways in HT22 Hippocampal Neurons.

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    Wei Jiang

    Full Text Available Increasing evidence shows that oxidative stress and the hyperphosphorylation of tau protein play essential roles in the progression of Alzheimer's disease (AD. Quercetin is a major flavonoid that has anti-oxidant, anti-cancer and anti-inflammatory properties. We investigated the neuroprotective effects of quercetin to HT22 cells (a cell line from mouse hippocampal neurons. We found that Okadaic acid (OA induced the hyperphosphorylation of tau protein at Ser199, Ser396, Thr205, and Thr231 and produced oxidative stress to the HT22 cells. The oxidative stress suppressed the cell viability and decreased the levels of lactate dehydrogenase (LDH, superoxide dismutase (SOD, mitochondria membrane potential (MMP and Glutathione peroxidase (GSH-Px. It up-regulated malondialdehyde (MDA production and intracellular reactive oxygen species (ROS. In addition, phosphoinositide 3 kinase/protein kinase B/Glycogen synthase kinase3β (PI3K/Akt/GSK3β and mitogen activated protein kinase (MAPK were also involved in this process. We found that pre-treatment with quercetin can inhibited OA-induced the hyperphosphorylation of tau protein and oxidative stress. Moreover, pre-treatment with quercetin not only inhibited OA-induced apoptosis via the reduction of Bax, and up-regulation of cleaved caspase 3, but also via the inhibition of PI3K/Akt/GSK3β, MAPKs and activation of NF-κB p65. Our findings suggest the therapeutic potential of quercetin to treat AD.

  20. Okadaic acid (1 microM) accelerates S phase and mitosis but inhibits heterochromatin replication and metaphase anaphase transition in Vicia faba meristem cells.

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    Polit, Justyna Teresa; Kazmierczak, Andrzej

    2007-01-01

    Protein kinases and phosphatases are the foremost agents which take part in cell cycle regulation in both plants and other eukaryotes. Protein kinases are a very well examined group of proteins with respect to chemical structure and function. Nowadays protein phosphatases, including PP1 and PP2A belonging to the PSP family, are the focus of interest. Okadaic acid (OA) which is a specific inhibitor of protein phosphatase activity is widely used to study them. In the present research, the involvement of OA-sensitive phosphatases in the regulation of progression of the plant cell cycle was analysed (in planta) using Vicia faba root meristems synchronized with hydroxyurea and divided into five series. Each series was treated with 1 muM OA for 3 h for different time periods corresponding to the consecutive cell cycle phases. The results showed that in the OA-treated cells DNA replication and mitosis began earlier than in the control cells, since G(1) and G(2) phases were significantly shorter and the H1 histone kinases activity was higher. Moreover, autoradiography and morphological analyses of mitotic figures revealed that the OA-treated cells entered mitosis before the end of heterochromatin replication. An immunocytochemical search showed that earlier initiation of S phase in the OA-treated cells correlated with more abundant phosphorylation of Rb-like protein in comparison with the control cells. OA also induced significant condensation of metaphase chromosomes and blocked metaphase-anaphase transition.

  1. Production of monoclonal antibody for okadaic acid and its utilization in an ultrasensitive enzyme-linked immunosorbent assay and one-step immunochromatographic strip.

    Science.gov (United States)

    Liu, Biing-Hui; Hung, Chun-Tse; Lu, Chuan-Chen; Chou, Hong-Non; Yu, Feng-Yih

    2014-02-12

    Okadaic acid (OA) is a common marine biotoxin that accumulates in bivalves and causes diarrhetic shellfish poisoning (DSP). This study generated a monoclonal antibody (mAb) specific to OA from a hybridoma cell line, 6B1A3, which was obtained by fusion of myeloma cells (P3/NS1/1-AG4-1) with spleen cells isolated from a BALB/c mouse immunized with OA-γ-globulin. The 6B1A3 mAb belongs to the immunoglobulin G1 (κ chain) isotype. Both competitive direct and indirect enzyme-linked immunosorbent assays (ELISAs) were established for characterization of the antibody. The concentrations causing 50% inhibition of binding of OA-horseradish peroxidase to the antibody by OA were calculated to be 0.077 ng/mL in the cdELISA. A rapid and sensitive mAb-based gold nanoparticle immunochromatographic strip was also established. This proposed strip has a detection limit of 5 ng/mL for OA and can be finished in 10 min. Extensive analyses of 20 seafood samples with ELISA revealed that 10 were slightly contaminated with OA, with a mean concentration of 0.892 ng/g. Analysis of OA in shellfish samples showed that data acquired by the immunochromatographic strip agreed well with those acquired by the ELISA. The mAb-based ELISA and immunochromatographic strip assay developed in this study have adequate sensitivity and accuracy for rapid screening of OA in shellfish samples.

  2. Effect of okadaic acid and calyculin-A, two protein phosphatase inhibitors, on thyrotropin-stimulated triiodothyronine secretion in cultured sheep thyroid cells.

    Science.gov (United States)

    Arufe, M C; Beckett, G J; Durán, R; Alfonso, M

    1999-12-01

    We have studied the effect of two protein phosphatase inhibitors on thyrotropin (TSH)-stimulated triiodothyronine (T3) production by sheep thyroid cells grown in primary culture. Incubation of sheep thyrocytes with okadaic acid (OA) and calyculin-A (CL-A), two potent inhibitors of type 1 (PP1) and type 2A (PP2A) protein phosphatases, resulted in an increase of TSH-stimulated T3 production. This effect was detected using concentrations as low as 0.1 pM with OA and 1 fM with CL-A. An inhibitory effect on T3 production, due to cellular death, was observed with 6 nM OA and 1 nM CL-A. In the absence of TSH, OA or CL-A had no effect on T3 production by thyrocytes. Forskoline (10 microM), an activator of adenylate cyclase, increased the basal and TSH-stimulated T3 release by sheep thyroid cells; this effect was increased by OA in cells grown in the basal state but not in the presence of TSH. These results suggest that the marine toxins OA and CL-A, two potent inhibitors of PP-1 and PP-2A, have significant stimulatory effects on T3 secretion promoted by TSH and FK. These observations indicate that these proteins could be important mediators of thyroid hormone production.

  3. The Prevalence of Antibiotic and Toothpaste Sensitivity found in Oral Streptococcal Isolates in Healthy Individuals in the Okada Community of Nigeria

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    Maureen U Okwu

    2017-04-01

    Full Text Available Background: This study aimed to determine the prevalence, antibiotic, and toothpaste sensitivity of oral streptococcal isolates in healthy individuals in the Okada community of Nigeria. Methods: Oral samples were collected from 230 volunteers and were subjected to standard microbiological tests. Antibacterial sensitivity tests were carried out on the streptococcal isolates that were obtained using a disk diffusion technique, and eight kinds of toothpaste (A-H were screened for their antibacterial effects on Streptococcus mutans (S. mutans. Results: The prevalence of oral streptococci found in this study was 26.1% and the predominant species was S. salivarius (13.9%. S. salivarius was highly resistant to cloxacillin (100% and Augmentin (96.9%, whilst resistance to gentamicin and erythromycin was low at 21.9% and 3.1% respectively. S. mutans were completely sensitive to gentamicin whilst resistance to erythromycin was 33.3%. The entire Streptococcus species showed the lowest resistance to erythromycin (20.0%, followed by gentamicin (31.7%. At 100 mg/mL all toothpaste samples had antibacterial effects on S. mutans. At 50 mg/mL all samples except toothpastes G and H inhibited the bacterium. Toothpastes A and E had the lowest minimum inhibitory concentration of 25 mg/mL. Conclusions: Toothpastes A and E were the most effective toothpastes of the eight assessed in this study.

  4. In Vitro Analysis of Early Genotoxic and Cytotoxic Effects of Okadaic Acid in Different Cell Types of the Mussel Mytilus galloprovincialis.

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    Prego-Faraldo, María Verónica; Valdiglesias, Vanessa; Laffon, Blanca; Eirín-López, José M; Méndez, Josefina

    2015-01-01

    Okadaic acid (OA) is the predominant biotoxin responsible for diarrhetic shellfish poisoning (DSP) syndrome in humans. While its harmful effects have been extensively studied in mammalian cell lines, the impact on marine organisms routinely exposed to OA is still not fully known. Few investigations available on bivalve molluscs suggest less genotoxic and cytotoxic effects of OA at high concentrations during long exposure times. In contrast, no apparent information is available on how sublethal concentrations of OA affect these organisms over short exposure times. In order to fill this gap, this study addressed for the first time in vitro analysis of early genotoxic and cytotoxic effects attributed to OA in two cell types of the mussel Mytilus galloprovincialis. Accordingly, hemocytes and gill cells were exposed to low OA concentrations (10, 50, 100, 200, or 500 nM) for short periods of time (1 or 2 h). The resulting DNA damage, as apoptosis and necrosis, was subsequently quantified using the comet assay and flow cytometry, respectively. Data demonstrated that (1) mussel hemocytes seem to display a resistance mechanism against early genotoxic and cytotoxic OA-induced effects, (2) mussel gill cells display higher sensitivity to early OA-mediated genotoxicity than hemocytes, and (3) mussel gill cells constitute more suitable systems to evaluate the genotoxic effect of low OA concentrations in short exposure studies. Taken together, this investigation provides evidence supporting the more reliable suitability of mussel gill cells compared to hemocytes to evaluate the genotoxic effect of low short-duration exposure to OA.

  5. The CHROMEVALOA Database: A Resource for the Evaluation of Okadaic Acid Contamination in the Marine Environment Based on the Chromatin-Associated Transcriptome of the Mussel Mytilus galloprovincialis

    Directory of Open Access Journals (Sweden)

    José M. Eirín-López

    2013-03-01

    Full Text Available Okadaic Acid (OA constitutes the main active principle in Diarrhetic Shellfish Poisoning (DSP toxins produced during Harmful Algal Blooms (HABs, representing a serious threat for human consumers of edible shellfish. Furthermore, OA conveys critical deleterious effects for marine organisms due to its genotoxic potential. Many efforts have been dedicated to OA biomonitoring during the last three decades. However, it is only now with the current availability of detailed molecular information on DNA organization and the mechanisms involved in the maintenance of genome integrity, that a new arena starts opening up for the study of OA contamination. In the present work we address the links between OA genotoxicity and chromatin by combining Next Generation Sequencing (NGS technologies and bioinformatics. To this end, we introduce CHROMEVALOAdb, a public database containing the chromatin-associated transcriptome of the mussel Mytilus galloprovincialis (a sentinel model organism in response to OA exposure. This resource constitutes a leap forward for the development of chromatin-based biomarkers, paving the road towards the generation of powerful and sensitive tests for the detection and evaluation of the genotoxic effects of OA in coastal areas.

  6. β-Secretase inhibitor increases amyloid-β precursor protein level in rat brain cortical primary neurons induced by okadaic acid

    Institute of Scientific and Technical Information of China (English)

    YU Chun-Jiang; WANG Wei-zhi; LIU Wei

    2008-01-01

    Background Senile plaques and neurofibrillary tangles (NFTs) represent two of the major histopathological hallmarks of Alzheimer's disease (AD). The plaques are primarily composed of aggregated amyloid β (Aβ) peptides. The processing of amyloid-β precursor protein (AβPP) in okadaic acid (OA)-induced tau phosphorylation primary neurons was studied.Methods Primary cultures of rat brain cortical neurons were treated with OA and β-secretase inhibitor. Neurons' viability was measured. AβPP processing was examined by immunocytochemistry and Western blotting with specific antibodies against the AβPP-N-terminus (NT) and AβPP-C-terminus (CT).Results Ten nrnol/L OA had a time-dependent suppression effect on primary neurons' viability. The suppression effect was alleviated markedly by pretreatment with β-secretase inhibitor. After OA treatment, both AβPP and β-C-terminal fragment (βCTF) were significantly increased in neurons. AβPP level was increased further in neurons pretreated with β-secretase inhibitor.Conclusions In OA-induced tau phosphorylation cell model, inhibition of β-secretase may protect neurons from death induced by OA. Because of increased accumulation of AβPP in neurons after OA treatment, more AβPP turns to be cleaved by β-secretase, producing neurotoxic βCTF. As a potential effective therapeutic target, β-secretase is worth investigating further.

  7. Inhibitory effect of polyunsaturated fatty acids on apoptosis induced by etoposide, okadaic acid and AraC in Neuro2a cells

    Directory of Open Access Journals (Sweden)

    Tomizawa,Kazuhito

    2007-06-01

    Full Text Available Neuronal apoptosis is involved in neurodegenerative diseases such as Alzheimer's disease and Parkinson.s disease. An efficient means of preventing it remains to be found. Some n-3 polyunsaturated fatty acids (PUFAs such as docosahexaenoic acid (DHA, 22 : 6n-3 and eicosapentaenoic acid (EPA, 20 : 5n-3 have been reported to be protective against the neuronal apoptosis and neuronal degeneration seen after spinal cord injury (SCI [1]. However, it is unclear which kinds of PUFAs have the most potent ability to inhibit neuronal apoptosis and whether the simultaneous treatment of PUFAs inhibits the apoptosis. In the present study, we compared the abilities of various n-3- and n-6- PUFAs to inhibit the apoptosis induced after the administration of different apoptotic inducers, etoposide, okadaic acid, and AraC, in mouse neuroblastoma cells (Neuro2a. Preincubation with DHA (22 : 6n-3, eicosapentaenoic acid (EPA, 20 : 5n-3, alpha-linolenic acid (alpha-LNA, 18 : 3n-3, linoleic acid (LA, 18 : 2n-6, arachidonic acid (AA, 20 : 4n-3, and gamma-linolenic acid (gamma-LNA, 18 : 3n-6 significantly inhibited caspase-3 activity and LDH leakage but simultaneous treatment with the PUFAs had no effect on the apoptosis of Neuro2a cells. There were no significant differences of the anti-apoptotic eff ect among the PUFAs. These results suggest that PUFAs may not be effective for inhibiting neuronal cell death after acute and chronic neurodegenerative disorders. However, dietary supplementation with PUFAs may be beneficial as a potential means to delay the onset of the diseases and/or their rate of progression.

  8. Algal toxins and reverse osmosis desalination operations: laboratory bench testing and field monitoring of domoic acid, saxitoxin, brevetoxin and okadaic acid.

    Science.gov (United States)

    Seubert, Erica L; Trussell, Shane; Eagleton, John; Schnetzer, Astrid; Cetinić, Ivona; Lauri, Phil; Jones, Burton H; Caron, David A

    2012-12-01

    The occurrence and intensity of harmful algal blooms (HABs) have been increasing globally during the past few decades. The impact of these events on seawater desalination facilities has become an important topic in recent years due to enhanced societal interest and reliance on this technology for augmenting world water supplies. A variety of harmful bloom-forming species of microalgae occur in southern California, as well as many other locations throughout the world, and several of these species are known to produce potent neurotoxins. These algal toxins can cause a myriad of human health issues, including death, when ingested via contaminated seafood. This study was designed to investigate the impact that algal toxin presence may have on both the intake and reverse osmosis (RO) desalination process; most importantly, whether or not the naturally occurring algal toxins can pass through the RO membrane and into the desalination product. Bench-scale RO experiments were conducted to explore the potential of extracellular algal toxins contaminating the RO product. Concentrations exceeding maximal values previously reported during natural blooms were used in the laboratory experiments, with treatments comprised of 50 μg/L of domoic acid (DA), 2 μg/L of saxitoxin (STX) and 20 μg/L of brevetoxin (PbTx). None of the algal toxins used in the bench-scale experiments were detectable in the desalinated product water. Monitoring for intracellular and extracellular concentrations of DA, STX, PbTx and okadaic acid (OA) within the intake and desalinated water from a pilot RO desalination plant in El Segundo, CA, was conducted from 2005 to 2009. During the five-year monitoring period, DA and STX were detected sporadically in the intake waters but never in the desalinated water. PbTx and OA were not detected in either the intake or desalinated water. The results of this study demonstrate the potential for HAB toxins to be inducted into coastal RO intake facilities, and the

  9. Algal toxins and reverse osmosis desalination operations: Laboratory bench testing and field monitoring of domoic acid, saxitoxin, brevetoxin and okadaic acid

    KAUST Repository

    Seubert, Erica L.

    2012-12-01

    The occurrence and intensity of harmful algal blooms (HABs) have been increasing globally during the past few decades. The impact of these events on seawater desalination facilities has become an important topic in recent years due to enhanced societal interest and reliance on this technology for augmenting world water supplies. A variety of harmful bloom-forming species of microalgae occur in southern California, as well as many other locations throughout the world, and several of these species are known to produce potent neurotoxins. These algal toxins can cause a myriad of human health issues, including death, when ingested via contaminated seafood. This study was designed to investigate the impact that algal toxin presence may have on both the intake and reverse osmosis (RO) desalination process; most importantly, whether or not the naturally occurring algal toxins can pass through the RO membrane and into the desalination product. Bench-scale RO experiments were conducted to explore the potential of extracellular algal toxins contaminating the RO product. Concentrations exceeding maximal values previously reported during natural blooms were used in the laboratory experiments, with treatments comprised of 50 μg/L of domoic acid (DA), 2 μg/L of saxitoxin (STX) and 20 μg/L of brevetoxin (PbTx). None of the algal toxins used in the bench-scale experiments were detectable in the desalinated product water. Monitoring for intracellular and extracellular concentrations of DA, STX, PbTx and okadaic acid (OA) within the intake and desalinated water from a pilot RO desalination plant in El Segundo, CA, was conducted from 2005 to 2009. During the five-year monitoring period, DA and STX were detected sporadically in the intake waters but never in the desalinated water. PbTx and OA were not detected in either the intake or desalinated water. The results of this study demonstrate the potential for HAB toxins to be inducted into coastal RO intake facilities, and the

  10. The Research of Biosensor and Bionic e-Eye for Rapid Detection of Okadaic Acid on-Site%现场快速检测大田软海绵酸的传感器与仪器的研究

    Institute of Scientific and Technical Information of China (English)

    邱先鑫; 苏凯麒; 田玉兰; 邹瞿超; 方佳如; 李蓉; 王平

    2016-01-01

    Based onEnzyme-linked immunosorbent assay(ELISA),test kit,namely,enzyme sensor and the corre-sponding instrument was prepared,Bionic e-Eye for rapid,effective and quantitative detection of okadaic acid(OA) on-site. The detection limit of the kit is 0.19μg/L and the range is among 0.2μg/L and 5μg/L. The recovery rate is among 75%and 125%and the accuracy is within±15%. The performance of Bionic e-Eye is consistent with micro-plate reader and high performance liquid chromatography(HPLC). In addition,without artificial calculation,the instrument can show the results directly on the screen,which is very suitable for rapid detection,and will be a new technology for rapid and quantitative detection of OA on site.%研究并建立针对大田软海绵酸OA(okadaic acid)快速、有效的酶联免疫吸附试验ELISA(Enzyme-Linked Immunosorbent Assay)定量检测方法,制备了定量检测试剂盒-生物酶传感器,并研发配套的现场快速检测仪器-仿生电子眼(Bionic e-Eye),实现对OA的快速检测.对标准样品的参数进行测定,该OA试剂盒的检测限为0.19μg/L,检测范围为0.2μg/L~5μg/L;样品回收率为75%~125%,精密度在±15%以内.将Bionic e-Eye的检测结果和酶标仪及高效液相色谱HPLC(high performance liquid chromatog-raphy)所测数据的结果进行了比较,结果表明,Bionic e-Eye的性能与酶标仪的检测结果一致.此外,该仪器可以直接得出检测结果,不需要人工计算处理,适用于现场的快速检测,将是一种新的现场快速定量检测OA的技术手段.

  11. 秘鲁鱿鱼和日本海鱿鱼营养成分分析与评价%Analysis and Evaluation of Nutritional Compositions of Dosidicus gigas and Onychoteuthis borealijaponicus okada

    Institute of Scientific and Technical Information of China (English)

    杨宪时; 王丽丽; 李学英; 黄洪亮; 迟海

    2013-01-01

    以秘鲁鱿鱼(Dosidicus gigas)和日本海鱿鱼(Onychoteuthis borealijaponicus okada)为原料,对其胴体的营养成分进行了分析比较与评价.研究表明,秘鲁鱿鱼和日本海鱿鱼都是低脂肪高蛋白食品,两者的蛋白质、脂肪、灰分含量均相近,水分含量前者显著高于后者(P<0.05).两者的磷P、锌Zn、铜Cu含量没有显著性差别,日本海鱿鱼钙Ca的含量为(2.31‰)高于秘鲁鱿鱼(1.64‰).秘鲁鱿鱼的氨基酸总量、∑EAA/∑AA均高于日本海鱿鱼,按照FAO/WHO建议的氨基酸评分标准模式,两者均属于优质蛋白质.两种鱿鱼含量最高的氨基酸均为谷氨酸,以AAS模式来看,虽然两种鱿鱼必须氨基酸指数不同,但都大于0.5,说明鱿鱼胴体营养丰富且符合人体对氨基酸的需求.秘鲁鱿鱼含有10种不饱和脂肪酸,日本海鱿鱼含有7种.与其他海产品相比较,鱿鱼的DHA含量较高,营养丰富,是具有较高开发前景的优质海产品.

  12. Tadashi Tanabe. Diffusion of the Greek gesture of touching another’s chin with raised hand in the East

    OpenAIRE

    Messina, Vito

    2016-01-01

    The gesture of touching or grasping another person’s chin with one hand supposedly originated in Greece. It was widespread in the ancient Near and Far East during the Hellenistic period, and survived for a long time even though it apparently became sporadic. Several scholars have speculated on this gesture’s meaning, which is still obscure. No exhaustive survey has been made of its diffusion in Asia. This article comments on several documents from ancient Persia and Gandhara that present this...

  13. Detecção de ácido ocadaico em cultivo de mexilhões Perna perna, Angra dos Reis, RJ Okadaic acid detection in mussel cultivation Perna perna, Angra dos Reis, RJ

    Directory of Open Access Journals (Sweden)

    Geisi Ferreira Mariné

    2010-02-01

    Full Text Available A ficotoxina ácido ocadaico (AO é produzida por um grupo de microalgas conhecidas como dinoflagelados. Os mexilhões, ao se alimentarem dessas microalgas, acumulam a toxina em sua glândula digestiva, desencadeando a Síndrome ou Envenenamento Diarreico por Moluscos (EDM no ser humano. Os sintomas se apresentam em torno de 30 minutos após o consumo do molusco contaminado, variando entre náuseas, dores abdominais, vômitos e diarreia. Quando a ingestão da toxina acontece em quantidades inferiores a 48µg g-1, os sintomas não se desenvolvem, porém seu consumo continuado favorece o surgimento de tumores no trato gastrointestinal em razão do poder carcinogênico do AO. Este estudo pretendeu detectar e quantificar a toxina diarreica AO em mexilhões Perna perna coletados entre os meses de maio e outubro de 2006. A detecção do AO nos mexilhões foi realizada por Cromatografia Líquida de Alta Eficiência com Detecção Fluorimétrica (CLAE-DF. Os resultados cromatográficos indicaram a presença da toxina AO em baixas concentrações, em todas as amostras de mexilhões obtidas de maio a outubro de 2006. Os resultados indicam a necessidade da elaboração e aplicação efetiva de um programa de controle higiênico-sanitário dos moluscos, assim como o monitoramento do ambiente aquático, objetivando, acima de tudo, a segurança da saúde pública.Okadaic acid (OA is a phycotoxin produced by a group of microalgae known as Dino-flagellates. When mussels feed themselves from this micro seaweed the toxin accumulates in their hepatopancreas, triggering the Syndrome or Diarrhetic Shellfish Poisoning (DSP in the human being. The symptoms appear around 30 minutes after the consumption of contaminated mussels and include abdominal nauseas, pains, vomits and diarrhea. When the toxin ingestion happens in amounts lower than 48µg g-1, the above described symptoms do not develop. However, the continued consumption favors the emergence of tumors in the

  14. 白细胞介素-10对冈田酸诱导的阿尔茨海默病模型大鼠的保护作用%Interleukin-10 prevents rats from okadaic acid-induced Alzheimer's disease

    Institute of Scientific and Technical Information of China (English)

    李冰; 毛丰; 方小霞; 邱一华

    2013-01-01

    Objective:To explore the protective effects of interleukin-10 (IL-10) pretreatment on the behavioral and molecular biochemical changes of Alzheimer'disease (AD) rat models and its possible mechanism.Methods:Okadaic acid (OA) was microinjected into the hippocampus of rats to establish the AD rat models.The escape latency of rats was tested by water maze.Western-blot method was used to detect the expression of protein phosphatase 2A (PP2A) and amyloid precursor protein (APP) in the hippocampus.Simultaneously,the ratio of CD4+ cells to the CD8+ cells in the mesenteric lymph node cells was examined by flowcytometry.Results:The latent period in water maze of rats that were injected with OA in the hippocampus was significantly increased,and the latent period of the rats with high concentration of OA injection was longer than that of the rats with low concentration of OA injection.The PP2A protein expression in hippocampus after the OA injection was down-regulated,and the inhibitory effect of OA on PP2A protein expression was enhanced as the OA concentrations increased.Conversely,APP protein expression in hippocampus was increased with the elevated concentrations of OA injected in the hippocampus.After IL-10 and OA were injected into the rat hippocampus respectively,the latent period of water maze was significantly lower than that of the AD rats only with the OA injection.IL-10 reversed the inhibitory effect of OA on PP2A expression and alleviated the augument of APP;furthermore,IL-10 reversed the increasing of CD4+/CD8+ induced by OA and caused the CD4+/CD8+ return to the control level.Conclusion:AD-like changes can be induced by the microinjection of OA into the hippocampus.IL-10 can reverse the AD-like changes induced by OA,and the effects of IL-10 are dose-dependent and also closely related to its inhibition of inflammatory reaction.%目的:观察细胞因子白细胞介素-10(IL-10)预处理对阿尔茨海默病(Alzheimer' disease,AD)模型鼠行为学和分子生

  15. 人参皂苷Rg1对冈田酸所致大鼠脑片tau蛋白磷酸化的影响%Effects of gensenoside Rg1 on tau protein phosphorylation induced by okadaic acid in rat brain slices

    Institute of Scientific and Technical Information of China (English)

    李玺; 刘颖; 袁海峰; 权乾坤

    2010-01-01

    目的:观察人参皂苷 Rg1 对阿尔茨海默病(Alzheimer's disease,AD)样 tau 蛋白磷酸化大鼠脑片模型中磷酸化 tau 蛋白(phosphorylated tau protein,P-tau)、蛋白磷酸酶 2A(protein phosphatase 2A,PP2A)及 tau 蛋白表达的影响,以研究其对 tau 蛋白磷酸化的抑制作用机制.方法:将 5 周龄雄性 Wistar 大鼠脑片(含皮层和海马)随机分为空白对照组、模型组和低、中、高浓度人参皂苷 Rg1 组,每组 10 张脑片.脑片置于人工脑脊液中培养.人参皂苷 Rg1 组培养液中首先加入人参皂苷Rg1 使其浓度分别为 60、120 和 240 μmol/L,作用 2 h.模型组和 3 个浓度人参皂苷 Rg1 组培养液中分别加入冈田酸(okadaic acid,OA),使其浓度分别为 1 μmol/L,作用 3 h,空白对照组不加任何处理.采用免疫组织化学染色、图像分析技术等方法,检测皮层和海马 P-tau、PP2A 和 tau 蛋白的表达水平.结果:与空白对照组比较,模型组 P-tau 蛋白的表达增加(P<0.01),PP2A 和 tau 蛋白的表达水平降低(P<0.01,P<0.05);3个浓度人参皂苷 Rg1 组与模型组比较,P-tau 蛋白的表达减少(P<0.01),PP2A 和 tau 蛋白的表达增加(P<0.01,P<0.05),其中以高浓度人参皂苷 Rg1 效果最佳.结论:人参皂苷Rg1 可以上调 AD 样 tau 蛋白磷酸化大鼠脑片模型中 PP2A 的表达从而促进 P-tau 的去磷酸化,以此途径抑制 tau 蛋白磷酸化.

  16. Saxitoxins and okadaic acid group: accumulation and distribution in invertebrate marine vectors from Southern Chile.

    Science.gov (United States)

    García, Carlos; Pérez, Francisco; Contreras, Cristóbal; Figueroa, Diego; Barriga, Andrés; López-Rivera, Américo; Araneda, Oscar F; Contreras, Héctor R

    2015-01-01

    Harmful algae blooms (HABs) are the main source of marine toxins in the aquatic environment surrounding the austral fjords in Chile. Huichas Island (Aysén) has an history of HABs spanning more than 30 years, but there is limited investigation of the bioaccumulation of marine toxins in the bivalves and gastropods from the Region of Aysén. In this study, bivalves (Mytilus chilenses, Choromytilus chorus, Aulacomya ater, Gari solida, Tagelus dombeii and Venus antiqua) and carnivorous gastropods (Argobuccinum ranelliformes and Concholepas concholepas) were collected from 28 sites. Researchers analysed the accumulation of STX-group toxins using a LC with a derivatisation post column (LC-PCOX), while lipophilic toxins (OA-group, azapiracids, pectenotoxins and yessotoxins) were analysed using LC-MS/MS with electrospray ionisation (+/-) in visceral (hepatopancreas) and non-visceral tissues (mantle, adductor muscle, gills and foot). Levels of STX-group and OA-group toxins varied among individuals from the same site. Among all tissue samples, the highest concentrations of STX-group toxins were noted in the hepatopancreas in V. antiqua (95 ± 0.1 μg STX-eq 100 g(-1)), T. dombeii (148 ± 1.4 μg STX-eq 100 g(-1)) and G. solida (3232 ± 5.2 μg STX-eq 100 g(-1); p mantle > adductor muscle for the STX-group toxins and foot > digestive gland for the OA-group toxins. These results gave a better understanding of the variability and compartmentalisation of STX-group and OA-group toxins in different bivalve and gastropod species from the south of Chile, and the analyses determined that tissues could play an important role in the biotransformation of STX-group toxins and the retention of OA-group toxins.

  17. Preliminary study of the effects of Okadaic Acid in the intestinal tract of mouse

    Directory of Open Access Journals (Sweden)

    Diego Alberto Fernández

    2014-06-01

    Our results support the little morphological effect of OA on intestinal cells. However, more interdisciplinary research is needed to obtain precise and reliable data to clarify the effects of OA in the intestinal epithelium and its relation with the diarrhea.

  18. 2 obras del arquitecto Shin'Ichi Okada – Japón

    Directory of Open Access Journals (Sweden)

    Editorial, Equipo

    1973-11-01

    Full Text Available Niigata school of odontology. The five buildings that currently make up the school, although handled in the same way with the same materials, have different shapes and heights, depending on the function; nevertheless, they form a harmonious whole. They are arranged in the shape of an L at one end of which the hospital was located with its various clinical sections and rooms for classes and lectures. Directly joined to the hospital is the main building in which the administrative area, offices, library and reading rooms are distributed. The other three buildings, for practical and theoretical classes, have been linked together by means of outside hall and corridors. The complex is completed with sports facilities and gardened areas which help to create an environment pleasing to the students. Gymnasium of the odontological university of Chiyoda (Tokyo. The premise that guided the project was that the large architectural mass needed would not clash with the smaller surrounding buildings. To this end glass walls were used which reflect the images of its surroundings. The gymnasium, with a rectangular base, has two large blocks of reinforced concrete at its ends which serve as the structural support and service nuclei. The total volume is divided into three well-differentiated spaces: the base, open, which is used as a parking lot; the main gymnasium; and the training hall. Between the latter two, the dressing rooms have been located. The technical stations were situated in the basement.Facultad de odontología de Niigata. Los cinco edificios que actualmente constituyen ia Facultad, aunque tratados de la misma manera y con los mismos materiales, son de distintas formas y alturas, de acuerdo con su función, formando, sin embargo, un conjunto armónico. En su disposición adoptan la forma de una L, en uno de cuyos extremos se situó el hospital, con sus distintas secciones clínicas y aulas para clases y conferencias. Unido directamente a éste se encuentra el edificio principal, en el que se distribuyen la zona de administración, oficinas, biblioteca, y salas de lectura. Enlazados mediante pasillos y corredores exteriores se han dispuesto los otros tres edificios, destinados a clases prácticas y teóricas. El conjunto se completa con instalaciones deportivas y zonas ajardinadas, que contribuyen a la consecución de un ambiente agradable para los estudiantes. Gimnasio de la universidad odontológica de Chiyoda (Tokio. La premisa que dirigió el proyecto fue que la gran mole edificada necesaria no desentonara con los edificios circundantes, de tamaño más reducido. Con este fin se emplearon paredes de vidrio que reflejan las imágenes de los alrededores. El gimnasio, de planta rectangular, tiene en sus extremos dos grandes bloques de hormigón armado, que constituyen el sostén estructural y sirven como núcleos de servicio. El volumen total se divide en tres espacios bien diferenciados: la base, abierta, que se utiliza como aparcamiento; el gimnasio principal, y el salón de entrenamiento. Entre estos dos últimos se han situado los vestuarios. Los locales técnicos se ubicaron en el sótano.

  19. The molecular basis for the high photosensitivity of rhodopsin.

    Science.gov (United States)

    Liu, Robert S H; Colmenares, Leticia U

    2003-12-09

    Based on structural information derived from the F NMR data of labeled rhodopsins, rhodopsin crystal structure, and excited-state properties of model polyenes, we propose a molecular mechanism that accounts specifically for the causes of the well-known enhanced photoreactivity of rhodopsin (increased rates and quantum yield of isomerization). It involves the key features of close proximity of C-187 to H-12 and chromophore bond lengthening upon light absorption. The resultant "sudden punch" to H-12 triggers dual processes of decay of the Franck-Condon-excited rhodopsin, a productive directed photoisomerization and a nonproductive decay returning to the ground state as two separate molecular pathways [based on real-time fluorescence results of Chosrowjan, H., Mataga, N., Shibata, Y., Tachibanaki, S., Kandori, H., Shichida, Y., Okada, T. & Kouyama, T. (1998) J. Am. Chem. Soc. 120, 9706-9707]. The two processes are controlled by the local protein structure: an empty space provided by the intradiscal loop connecting transmembrane helices 4 and 5 and a protein wall composed of amino acid units in transmembrane 3. Suggestions, involving retinal analogs and rhodopsin mutants, to improve the unusually high photosensitivity of rhodopsin are proposed.

  20. Accumulation and depuration of okadaic acid esters in the European green crab ( Carcinus maenas ) during a feeding study

    DEFF Research Database (Denmark)

    Jørgensen, Kevin; Cold, Ulrik; Fischer, Knud

    2008-01-01

    Soft shell crab is a seafood delicacy in many parts of the world. In Denmark, it has been investigated whether a commercial production of soft shell European green crabs (Carcinus maenas) would be feasible. In relation to this, a feeding study was performed to examine if occurrence of DSP toxins ...

  1. Behaviors of sea water studied with chemical transient tracers. Lecture by the member awarded the Okada prize of the Oceanographic Society of Japan for 1996

    Energy Technology Data Exchange (ETDEWEB)

    Watanabe, Y.W. [National Inst. for Resources and Environment, Tsukuba, Ibaraki (Japan)

    1997-02-01

    Chemical tracers are useful tools for clarifying the behaviors of sea water in the ocean. The present article reviews my works concerning chemical tracers. Based on my chemical tracers data, it was concluded that the turnover time of the Japan Sea deep water and the residence time of water within the Japan Sea were about 100 years and 1000 years, respectively, and that the exchange coefficient of CO{sub 2} in the Japan Sea was smaller than that in the North Pacific. Furthermore, chemical tracers and carbonate species data set in the North Pacific suggested that the production rate of intermediate water in the North Pacific was about 24 Sv and that the North Pacific subpolar region was an important sink of CO{sub 2} released from human activities after the industrial era. (author)

  2. Expanding Possibilities of Periodicals for Children in Asia and the Pacific. Report of the 1997 Training Course on Production of Periodicals for Children (Tokyo, October 1-15, 1997).

    Science.gov (United States)

    Asia/Pacific Cultural Centre for UNESCO, Tokyo (Japan).

    Following the proceedings of the training course on children's periodicals held in 1997 in Tokyo, this report contains the following articles: (1) "Children's Life and Magazines" (Jiro Saito); (2) "Periodical Picture Books to Develop Reading Skills of Children" (Tadashi Matsui); (3) "How to Produce Attractive Educational…

  3. Diarrhetic shellfish poisoning toxin esters in Danish blue mussels and surf clams

    DEFF Research Database (Denmark)

    Jørgensen, Kevin; Scanlon, Sine Hedegaard; Jensen, L.B.

    2005-01-01

    Until recently, little focus was given to the presence of diarrhetic shellfish poisoning ( DSP) toxin esters in seafood products. However, during the last few years, the occurrence of a high percentage of esters of the total amount of DSP toxins present in some seafood products has been observed....... Samples of Danish surf clams ( Spisola spp.) and blue mussels ( Mytilus edulis) from 1999 - 2004 were analysed by liquid chromatography coupled with tandem mass spectrometry ( LC/ MS/ MS) for the presence of DSP toxin esters. The samples contained only okadaic acid and esters of okadaic acid. The level...... of okadaic acid esters of the total okadaic acid equivalents ranged from 21 to 86%, mean 59%. The probability of a high percentage of okadaic acid esters seems to increase with higher amounts of total okadaic acid equivalents in the bivalves. The large prevalence of DSP toxin esters are of particular...

  4. A Combined Thermodynamic/Kinetic Modeling Approach to Predict SiC Recession Due to SiO2 Scale Volatility Under Combustion Environments

    Science.gov (United States)

    2010-02-01

    1987. 70(10): p. 750-759. 23. Okada, K., Otsuka , N., Change in Chemical-Composition of Mullite Formed from 2SiO2.3Al2O3 Xerogel During the...Pask, 1972 Aramaki and Roy, 1962 Aksay and Pask, 1975 Konopicky, 1956 Toropov and galakhov, 1951 Okada and Otsuka , 1987 Hamano, 1986 Klug, 1987 Prochazka

  5. Identity Politics in Women's Performance in Japan

    OpenAIRE

    2012-01-01

    In Japan, it was in the mid-1970s when women artists started to create their own professional theatre companies. This period also saw the development of the women's liberation movement in Japan, but there was no exchange between women theatre artists and activists. While the women artists explored a variety of issues in their work, with some few exceptions feminism was not their primary concern. This trend continues to this day, and accounts for why Tadashi Uchino argues that there has been n...

  6. Psychoactive substance use/abuse among students in Igbinedion ...

    African Journals Online (AJOL)

    ... use/abuse among students in Igbinedion University, Okada, Nigeria-new challenges. ... Journal Home > Vol 9, No 2 (2011) > ... Efforts must be made to regulate the sales of even some apparently harmless across the counter medications.

  7. African Journal of Biotechnology - Vol 8, No 12 (2009)

    African Journals Online (AJOL)

    Potential use of gas sensors in beef manure nutrient content estimations · EMAIL FREE ... Assessment of heavy metal accumulation and their translocation in plant ... Effect of cassava effluent on Okada natural water · EMAIL FREE FULL TEXT ...

  8. Protective Effect of Vitamin E on Nicotine Induced Reproductive ...

    African Journals Online (AJOL)

    1Igbinedion University, Department of Physiology, School of Basic Medical Sciences, Okada, Edo State, Nigeria ... nicotine on reproductive functions in male rats. .... The experiment was conducted in accordance ..... Male infertility, clinical ...

  9. ORIGINAL ARTICLE 230

    African Journals Online (AJOL)

    boaz

    aDepartment of Medical Laboratory Science, College of Health Science, Igbinedion University Okada, ... Further analysis of the malaria parasite density on pregnancy according to their ..... compared to the report ofDicko (31), who observed.

  10. Ainult kaks küsimust / Evelyn Raudsepp

    Index Scriptorium Estoniae

    Raudsepp, Evelyn

    2011-01-01

    Rahvusvahelise etenduskunstide festivali POT sotsiaalmeedia juht Evelyn Raudsepp festivali vastukajadest, populaarsematest etendustest, Toshiki Okada lavastusest "Hot Pepper, Air Conditioner, and the Farewell Speech", Kornél Mundruczó lavastusest "Hard To Be A God"

  11. Ainult kaks küsimust / Evelyn Raudsepp

    Index Scriptorium Estoniae

    Raudsepp, Evelyn

    2011-01-01

    Rahvusvahelise etenduskunstide festivali POT sotsiaalmeedia juht Evelyn Raudsepp festivali vastukajadest, populaarsematest etendustest, Toshiki Okada lavastusest "Hot Pepper, Air Conditioner, and the Farewell Speech", Kornél Mundruczó lavastusest "Hard To Be A God"

  12. Stemcell Information: SKIP000812 [SKIP Stemcell Database[Archive

    Lifescience Database Archive (English)

    Full Text Available pes. Yamashita A, Morioka M, Kishi H, Kimura T, Yahara Y, Okada M, Fujita K, Sawai H, Ikegawa S, Tsumaki N Nature 2014 513 7519 507-11 http://www.ncbi.nlm.nih.gov/pubmed/25231866 ...

  13. New blue emissive conjugated small molecules with low lying HOMO energy levels for optoelectronic applications

    Science.gov (United States)

    Trupthi Devaiah, C.; Hemavathi, B.; Ahipa, T. N.

    2017-03-01

    Versatile conjugated small molecules bearing cyanopyridone core (CP1-5), composed of various donor/acceptor moieties at position - 4 and - 6 have been designed, developed and characterized. Their solvatochromic studies were conducted and analyzed using Lippert-Mataga, Kamlet-Taft and Catalan solvent scales and interesting results were obtained. The polarizability/dipolarity of the solvent greatly influenced the spectra. The electrochemical studies were carried out using cyclic voltammetry to calculate the HOMO-LUMO energy levels. The study revealed that the synthesized conjugated small molecules possess low lying HOMO energy levels which can be exploited for application in various fields of optoelectronics.

  14. A Computationally Efficient Filter for Reducing Shot Noise in Low S/N Data.

    Directory of Open Access Journals (Sweden)

    Mami Okada

    Full Text Available Functional multineuron calcium imaging (fMCI provides a useful experimental platform to simultaneously capture the spatiotemporal patterns of neuronal activity from a large cell population in situ. However, fMCI often suffers from low signal-to-noise ratios (S/N. The main factor that causes the low S/N is shot noise that arises from photon detectors. Here, we propose a new denoising procedure, termed the Okada filter, which is designed to reduce shot noise under low S/N conditions, such as fMCI. The core idea of the Okada filter is to replace the fluorescence intensity value of a given frame time with the average of two values at the preceding and following frames unless the focused value is the median among these three values. This process is iterated serially throughout a time-series vector. In fMCI data of hippocampal neurons, the Okada filter rapidly reduces background noise and significantly improves the S/N. The Okada filter is also applicable for reducing shot noise in electrophysiological data and photographs. Finally, the Okada filter can be described using a single continuous differentiable equation based on the logistic function and is thus mathematically tractable.

  15. A case of traumatic intracranial vertebral artery injury presenting with life-threatening symptoms

    Directory of Open Access Journals (Sweden)

    Kishi S

    2012-04-01

    Full Text Available Seiji Kishi1, Kenji Kanaji2, Toshio Doi1, Tadashi Matsumura21Department of Nephrology, Tokushima University Hospital, Kuramoto-cho Tokushima, 2Department of General Internal Medicine, Rakuwakai Otowa Hospital, Otowachinji-cho Yamashina-ku Kyoto, JapanAbstract: Traumatic intracranial vertebral artery injury is a relatively rare but potentially fatal disease. We present a case of a 63-year-old man who presented with sudden onset of loss of consciousness after hitting his head. After immediate resuscitation, he showed quadriplegia and absence of spontaneous breathing. Brain and cervical spine magnetic resonance imaging revealed an atlantoaxial subluxation, fractured C2 odontoid process, left vertebral artery occlusion, and bilateral extensive ischemia in the medulla oblongata and high cervical spinal cord. Digital subtraction angiography demonstrated left vertebral artery dissection just below the level of vertebral body C2.Keywords: vertebral artery dissection, brainstem infarction, bilateral spinal cord infarction, neck trauma

  16. Cellular and molecular mechanisms underlying the action of ginsenoside Rg1 against Alzheimer's disease

    Institute of Scientific and Technical Information of China (English)

    Xi Li; Ming Li; Yuan Li; Qiankun Quan; Juan Wang

    2012-01-01

    Ginsenoside Rg1 inhibits oxidation, aging and cell apoptosis, and improves cognitive function. In this study, we pretreated rat brain tissue sections with ginsenoside Rg1, and established brain slice models of Alzheimer's disease induced by okadaic acid. The results revealed that ginsenoside Rg1 pretreatment suppressed the increase in phosphorylated Tau protein expression induced by incubation with okadaic acid, and reduced brain-derived neurotrophic factor expression. These results suggest that ginsenoside Rg1 upregulates brain-derived neurotrophic factor expression and inhibits Tau protein phosphorylation in brain slices from a rat model of Alzheimer's disease.

  17. EARNINGS FROM COMMERCIAL MOTORCYCLE OPERATIONS IN ...

    African Journals Online (AJOL)

    UDS-CAPTURED

    research gap seems obvious in these and other studies. ... that are willing-to-pay for okada services in exchange for rides by those who are willing-to- .... and to control for other factors such as gender, race, location and employment sectors.

  18. Management of Bottom Sediments Containing Toxic Substances: Proceedings of the U.S./Japan Experts Meeting (10th) Held at Kyoto, Japan on 30-31 October 1984.

    Science.gov (United States)

    1985-10-01

    Agency, Corvallis, 29. Okada, M., and Sudo, R. 1981. " Dissolved Oxygen Consumption in Lake Sediments," Management of Bottom Sediments Containing Toxic...in summer. b. Removal of the bottom sediment high in organic and nutrient concen- tration, along with the resultant reduction of dissolved oxygen consumption , will

  19. Lab-on-a-Chip Sensor for Monitoring Perchlorate in Ground and Surface Water

    Science.gov (United States)

    2012-02-01

    Detection with Microchip Electrophoresis Using a Bubble Cell.” Analytical Chemistry 80 (19): 7624-7630. Okada, T. 1997. “ Micellar Chromatography of...Electrophoresis .............................................................................................................. 9 2.5 Chromatography ...uses zwitterionic surfactants was immobilized on either a conventional or membrane-based stationary phase (electrostatic ion chromatography ) em

  20. Reliability-Based Shape Optimization using Stochastic Finite Element Methods

    DEFF Research Database (Denmark)

    Enevoldsen, Ib; Sørensen, John Dalsgaard; Sigurdsson, G.

    1991-01-01

    Application of first-order reliability methods FORM (see Madsen, Krenk & Lind [8)) in structural design problems has attracted growing interest in recent years, see e.g. Frangopol [4), Murotsu, Kishi, Okada, Yonezawa & Taguchi [9) and Sørensen [14). In probabilistically based optimal design...

  1. Reseña: "Crónica del pájaro que da cuerda al mundo" de Haruki Murakami

    OpenAIRE

    Falero Folgoso, Alfonso

    2000-01-01

    Protagonista: Okada Toru, varón de edad mediana, casado felizmente y con una posición laboral un tanto mediocre pero estable. Hemos de celebrar la feliz convergencia de estos dúos de japonés/española (o viceversa) que traducen del original con precisión y soltura. Reseña

  2. 1983-IJBCS-Article-Ehiaghe F.A

    African Journals Online (AJOL)

    hp

    Effect of academic stress on serum cortisol level and CD4 cell count in young male postgraduate students in Okada, ... 5Department of Medical Laboratory Science, University of Benin, Benin City, Nigeria. ... Those who abuse alcohol were excluded. ▫ Young male less ... Young male on performance enhancing drugs were ...

  3. The p38 MAP kinase inhibitor SB203580 enhances nuclear factor-kappa B transcriptional activity by a non-specific effect upon the ERK pathway

    NARCIS (Netherlands)

    Birkenkamp, KU; Tuyt, LML; Lummen, C; Wierenga, LTJ; Kruijer, W; Vellenga, E

    2000-01-01

    1 In the present study we investigated a possible role for the p38 mitogen-activated protein (MAP) kinase pathway in mediating nuclear factor-kappa B (NF-kappa B) transcriptional activity in the erythroleukaemic cell line TF-1. 2 TF-1 cells stimulated with the phosphatase inhibitor okadaic acid (OA)

  4. weSPOT: A Personal and Social Approach to Inquiry-Based Learning

    NARCIS (Netherlands)

    Mikroyannidis, Alexander; Okada, Alexandra; Scott, Peter; Rusman, Ellen; Specht, Marcus; Stefanov, Krassen; Boytchev, Pavel; Protopsaltis, Aristidis; Held, Paul; Hetzner, Sonia; Kikis-Papadakis, Kathy; Chaimala, Foteini

    2013-01-01

    Mikroyannidis, A., Okada, A., Scott, P., Rusman, E., Specht, M., Stefanov, K., Boytchev, P., Protopsaltis, A., Held, P., Hetzner, S., Kikis-Papadakis, K., & Chaimala, F. (in press). weSPOT: A Personal and Social Approach to Inquiry-Based Learning, Journal of Universal Computer Science Special Issue

  5. Entry into mitosis without Cdc2 kinase activation.

    Science.gov (United States)

    Gowdy, P M; Anderson, H J; Roberge, M

    1998-11-01

    Mouse FT210 cells at 39 degreesC cannot enter mitosis but arrest in G2 phase, because they lack Cdc2 kinase activity as a result of a temperature-sensitive lesion in the cdc2 gene. Incubation of arrested cells with the protein phosphatase 1 and 2A inhibitor okadaic acid induces morphologically normal chromosome condensation. We now show that okadaic acid also induces two other landmark events of early mitosis, nuclear lamina depolymerization and centrosome separation, in the absence of Cdc2 kinase activity. Okadaic acid-induced entry into mitosis is accompanied by partial activation of Cdc25C and may be prevented by tyrosine phosphatase inhibitors and by the protein kinase inhibitor staurosporine, suggesting that Cdc25C and kinases distinct from Cdc2 are required for these mitotic events. Using in-gel assays, we show that a 45-kDa protein kinase normally activated at mitosis is also activated by okadaic acid independently of Cdc2 kinase. The 45-kDa kinase can utilize GTP, is stimulated by spermine and is inhibited by heparin. These properties are characteristic of the kinase CK2, but immunoprecipitation studies indicate that it is not CK2. The data underline the importance of a tyrosine phosphatase, possibly Cdc25C, and of kinases other than Cdc2 in the structural changes the cell undergoes at mitosis, and indicate that entry into mitosis involves the activation of multiple kinases working in concert with Cdc2 kinase.

  6. weSPOT: A Personal and Social Approach to Inquiry-Based Learning

    NARCIS (Netherlands)

    Mikroyannidis, Alexander; Okada, Alexandra; Scott, Peter; Rusman, Ellen; Specht, Marcus; Stefanov, Krassen; Boytchev, Pavel; Protopsaltis, Aristidis; Held, Paul; Hetzner, Sonia; Kikis-Papadakis, Kathy; Chaimala, Foteini

    2013-01-01

    Mikroyannidis, A., Okada, A., Scott, P., Rusman, E., Specht, M., Stefanov, K., Boytchev, P., Protopsaltis, A., Held, P., Hetzner, S., Kikis-Papadakis, K., & Chaimala, F. (in press). weSPOT: A Personal and Social Approach to Inquiry-Based Learning, Journal of Universal Computer Science Special Issue

  7. Stemcell Information: SKIP001098 [SKIP Stemcell Database[Archive

    Lifescience Database Archive (English)

    Full Text Available formation ... No ... Minoru Okada 岡田 稔 Center for iPS Cell Research and Application..., Kyoto University 京都大学iPS細胞研究所 ... Information Only Center for iPS Cell Research and Application,Kyo

  8. Stemcell Information: SKIP000798 [SKIP Stemcell Database[Archive

    Lifescience Database Archive (English)

    Full Text Available cation, Kyoto University 京都大学iPS細胞研究所 ... Information Only Center for iPS Cell Research and Application...lysis Yes ... Yes Teratoma formation ... No ... Minoru Okada 岡田 稔 Center for iPS Cell Research and Appli

  9. Stemcell Information: SKIP001096 [SKIP Stemcell Database[Archive

    Lifescience Database Archive (English)

    Full Text Available ion ... No ... Minoru Okada 岡田 稔 Center for iPS Cell Research and Application..., Kyoto University 京都大学iPS細胞研究所 ... Information Only Center for iPS Cell Research and Application,Kyoto Uni

  10. Stemcell Information: SKIP001100 [SKIP Stemcell Database[Archive

    Lifescience Database Archive (English)

    Full Text Available formation ... No ... Minoru Okada 岡田 稔 Center for iPS Cell Research and Application..., Kyoto University 京都大学iPS細胞研究所 ... Information Only Center for iPS Cell Research and Application,Kyo

  11. Stemcell Information: SKIP001097 [SKIP Stemcell Database[Archive

    Lifescience Database Archive (English)

    Full Text Available ion ... No ... Minoru Okada 岡田 稔 Center for iPS Cell Research and Application..., Kyoto University 京都大学iPS細胞研究所 ... Information Only Center for iPS Cell Research and Application,Kyoto Uni

  12. Spectroscopic studies of biologically active coumarin laser dye: Evaluation of dipole moments by solvatochromic shift method

    Science.gov (United States)

    Koppal, V. V.; Muddapur, G. V.; Patil, N. R.; Melavanki, R. M.

    2016-05-01

    In this paper we attempted to record absorption and emission spectra of 2-acetyl-3H-benzo[f]chromen-3-one [2AHBC] laser dye in different solvents of varying polarities to investigate its solvatochromic behavior. The two electronic states dipole moments of 2AHBC are calculated using solvatochromic spectral shifts which are correlated with dielectric constant (ɛ) refractive index (n) of various solvents. A systematic approach is made to estimate ground and excited state dipole moments on the basis of different solvent correlation methods like Bilot-Kawski equations, Lippert-Mataga, Bakhsheiv, Kawaski-Chamma-Viallet and Reichardt methods. Dipole moments in the excited state was found to be higher than the ground state by confirming π→π* transition.

  13. 3-/3,5-Pyrrole-substituted BODIPY derivatives and their photophysical and electrochemical studies

    Indian Academy of Sciences (India)

    KARTHIKA J KADASSERY; AKANKSHA NIMESH; SANOJ RAJ; NEERAJ AGARWAL

    2016-09-01

    Nucleophilic substitution on 3-bromo/3,5-dibromo-4,4'-difluoro-8-(aryl)-4-bora-3a,4a-diaza-sindacene (BODIPY), substituted with anisyl or thienyl at meso positions, with neat pyrrole afforded the mono and di-pyrrole substituted BODIPYs 1–4 in good yields. Large bathochromic shifts, upto ∼180 nm in absorption maxima (581–682 nm), and fluorescence maxima (606–695 nm) were observed for these BODIPYs. Absorption and fluorescence properties were studied in different solvents to compare the effect of mono and di substitution on BODIPY. The Lippert-Mataga equations were used which predict strong polarization of monosubstituted BODIPYs. Electrochemical studies were carried out to find the oxidation potential and HOMO energy levels were calculated. Theoretical studies of 1–4 provide the insight on the electron density distribution in 1–4. Theoretical and experimental photo-physical studies in different solvents were correlated to findthe substituent effects on BODIPY.

  14. Dipole moment determination of 4-[N-(5,6,7,8-tetrahydroisoquinolinium-5-ylidene)methyl]-N,N-dialkylaniline iodides in solution.

    Science.gov (United States)

    Jędrzejewska, Beata; Pietrzak, Marek

    2011-09-01

    Electronic absorption and fluorescence spectra of eight hemicyanine dyes were recorded at room temperature in several solvents of different polarity. The spectral data were analyzed using the theory of solvatochromism, based on a dielectric continuum description of the solvent and the classical Onsager cavity model. They were used to evaluate the excited state dipole moment using methods applied by McRae, Lippert, Mataga and Bakhshiev. DFT calculations were carried out to estimate the ground state dipole moment and Onsager cavity radius. The difference in the excited and ground state dipole moments (μe-μg) of the molecule under study is positive. It means that the excited states of the dyes are more polar than the ground state. The increase in dipole moments upon excitation is explained in terms of the nature of the excited state and its resonance structures.

  15. A novel Love Wave biosensor for rapid and sensitive detection of marine toxins.

    Science.gov (United States)

    Zhang, Xi; Fang, Jiaru; Zou, Yingchang; Zou, Ling; Hu, Ning; Wang, Ping

    2015-01-01

    Marine toxins are produced by plankton and do a great harm to human through food chain by accumulating in shellfishes and fishes. It is highly required and favorable to develop novel methods for the rapid and efficient detection of marine toxins to avoid the poisoning cases that have occurred frequently in many countries. This study presents a real-time Love Wave biosensor for the rapid detection of okadaic acid (OA), which used HepG2 cell lines as the sensing elements. The results indicate that this cell-based biosensor can provide real-time information of cellular activities induced by okadaic acid and has a higher sensitivity than the conventional cell-based assay. It is suggested that this cell-based biosensor can be used as a convenient and efficient method for marine toxin detection, which has a great potential to contribute to avoid the harmful effects of marine toxins on the human health.

  16. Biosynthetic Studies on Water-Soluble Derivative 5c (DTX5c

    Directory of Open Access Journals (Sweden)

    José J. Fernández

    2012-10-01

    Full Text Available The dinoflagellate Prorocentrum belizeanum is responsible for the production of several toxins involved in the red tide phenomenon known as Diarrhetic Shellfish Poisoning (DSP. In this paper we report on the biosynthetic origin of an okadaic acid water-soluble ester derivative, DTX5c, on the basis of the spectroscopical analysis of 13C enriched samples obtained by addition of labelled sodium [l-13C], [2-13C] acetate to artificial cultures of this dinoflagellate.

  17. Ionizing Radiation Alters the Properties of Sodium Channels in Rat Brain Synaptosomes

    Science.gov (United States)

    1986-01-01

    Okada, 1970). The reactive products of water can concentration of BTX or veratridine, and 50 mM H EPES then interact with membrane lipids or proteins...action potential, Received October 18, 1985; accepted February 14, 1986. Abbreviations used: BTX , batrachotoxin DPH, 1.6-diphenyl- Address correspondence...structure and function of neuronal cubated for 2 min at 36’C. BTX or veratridine was then membranes may be the site of action. The interac- added, and the

  18. An Image Secret Sharing Method

    Science.gov (United States)

    2006-07-01

    M. E. Hellman, “On secret sharing systems,” vol. IT-29, no. 1, pp. 35–41, Jan. 1983. [10] K. Kurosawa , K. Okada, K. Sakano, W. Ogata, and S. Tsujii...Ed., Berlin, Germany, 1994, pp. 1–12. [14] W. Ogata and K. Kurosawa , “Some ba- sic properties of general nonperfect secret sharing schemes,” J.UCS

  19. Numerical Investigation for the Microstructural Effects on the Crack Growth Behavior of Particulate Composite Materials

    Science.gov (United States)

    2006-07-26

    When the damage constitutive law is adopted in an analysis, we perform an incremental analysis, just like the case of elastoplasticity (see Okada...isotropic elastoplasticity . 2.4 Some other issues associated with the damage constitutive law-initiation of nonlinear deformation Material...ABSTRACT In present investigation, analyses for the damage evolution behavior of particulate composite materials by using the finite element method

  20. A Crisis-Tempered Relationship

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    China and Japan cement their bonds in an effort to promote joint economic recovery On August 28,the third China Japan highlevel economic dialogue was held in Beijing. Chinese Vice Premier Wang Qishan and Japanese Foreign Minister Katsuya Okada co-chaired the dialogue.The two sides discussed promoting the economic recovery,as well as regional and global cooperation,and reached a series of agreements.

  1. Severe brain atrophy in the elderly as a risk factor for lower respiratory tract infection

    Directory of Open Access Journals (Sweden)

    Okada R

    2012-11-01

    Full Text Available Rieko Okada,1 Takashi Okada,2 Akira Okada,2 Hideyuki Muramoto,3 Masahisa Katsuno,4 Gen Sobue,4 Nobuyuki Hamajima11Department of Preventive Medicine, Nagoya University Graduate School of Medicine, 2Okada Medical Clinic, 3Muramoto Clinic, 4Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, JapanBackground: The purpose of this study is to determine whether elderly subjects with severe brain atrophy, which is associated with neurodegeneration and difficulty swallowing (dysphagia, are more susceptible to lower respiratory tract infections (LRTI, including pneumonia.Methods: The severity of brain atrophy was assessed by computed tomography in 51 nursing home residents aged 60–96 years. The incidence of LRTI, defined by body temperature ≥ 38.0°C, presence of two or more respiratory symptoms, and use of antibiotics, was determined over 4 years. The incidence of LRTI was compared according to the severity and type of brain atrophy.Results: The incidence rate ratio of LRTI was significantly higher (odds ratio 4.60, 95% confidence interval 1.18–17.93, fully adjusted P = 0.028 and the time to the first episode of LRTI was significantly shorter (log-rank test, P = 0.019 in subjects with severe brain atrophy in any lobe. Frontal and parietal lobe atrophy was associated with a significantly increased risk of LRTI, while temporal lobe atrophy, ventricular dilatation, and diffuse white matter lesions did not influence the risk of LRTI.Conclusion: Elderly subjects with severe brain atrophy are more susceptible to LRTI, possibly as a result of neurodegeneration causing dysphagia and silent aspiration. Assessing the severity of brain atrophy might be useful to identify subjects at increased risk of respiratory infections in a prospective manner.Keywords: brain atrophy, dysphagia, elderly, pneumonia, respiratory infection, white matter lesions

  2. Discovering a new analogue of thalidomide which may be used as a potent modulator of TNF-alpha production.

    Science.gov (United States)

    Fernández Braña, Miguel; Acero, Nuria; Añorbe, Loreto; Muñoz Mingarro, Dolores; Llinares, Francisco; Domínguez, Gema

    2009-09-01

    A new series of imide derivatives related to thalidomide were synthesized and evaluated as modulators of TNF-alpha production. These derivatives enhance TNF-alpha production using human leukemia HL-60 cells induced with 12-O-tetradecanoylphorbol 13-acetate (TPA), while inhibiting TNF-alpha production induced with okadaic acid (OA) in the same cell line. The diphenylmaleimide derivative 2f, was found to be the most active product, producing a strong modulation of the cytokine level.

  3. Use of pharmacist blood pressure telemonitoring systems in diagnosis of nocturnal hypertension in a young healthy male

    Directory of Open Access Journals (Sweden)

    Mizuno T

    2014-09-01

    Full Text Available Tomohiro Mizuno,1,* Chizuru Matsumoto,1,* Nobuko Nabetani,2 Yoshinari Yasuda,3 Tadashi Nagamatsu,1 Norimasa Umemura2 1Department of Analytical Pharmacology, Faculty of Pharmacy, Meijo University, Nagoya, Japan; 2Haruka Community Pharmacy, Nagoya, Japan; 3Department of Chronic Kidney Disease Initiatives, Nagoya University Graduate School of Medicine, Nagoya, Japan *These authors contributed equally to this work Abstract: Blood pressure (BP telemonitoring systems and pharmacist management programs were introduced into Haruka Community Pharmacy. A 22-year-old healthy male came to the community pharmacy, although he was not in a diseased state, he had been informed previously that he had a moderately high BP during a routine examination. He continued home BP telemonitoring for 28 days. A pharmacist intervention was conducted at 2 week intervals. His average nighttime systolic BP was higher than the daytime systolic BP. The pharmacist consulted a doctor based on the BP telemonitoring results, and ambulatory blood pressure monitoring (ABPM was initiated. The doctor detected nocturnal hypertension based on the results of ABPM monitoring. BP telemonitoring systems have been introduced into a small percentage of pharmacies in Japan, and this is the first case report for the usefulness of these systems in a community pharmacy. Keywords: community pharmacy, management, ambulatory blood pressure monitoring

  4. COPD is frequent in conditions of comorbidity in patients treated with various diseases in a university hospital

    Directory of Open Access Journals (Sweden)

    Akira Yamasaki

    2010-09-01

    Full Text Available Akira Yamasaki, Kiyoshi Hashimoto, Yasuyuki Hasegawa, Ryota Okazaki, Miki Yamamura, Tomoya Harada, Shizuka Ito, Soichiro Ishikawa, Hiroki Takami, Masanari Watanabe, Tadashi Igishi, Yuji Kawasaki, Eiji ShimizuDivision of Medical Oncology and Molecular Respirology, Department of Multidisciplinary Internal Medicine, Faculty of Medicine, Tottori University, JapanBackground: Chronic obstructive pulmonary disease (COPD is one of the leading causes of death and loss of disability-adjusted life-years. However, many COPD patients are not diagnosed because of underrecognition or underdiagnosis of this disease among many patients and physicians. One possible reason is underrecognition of spirometry. In this study, we examined the prevalence of airflow limitation and underlying disease in patients with airflow limitation.Methodology: From April 2006 to March 2008, patients who had spirometry performed were examined. The original disease of patients, pulmonary function tests, smoking status, and respiratory symptoms were surveyed from their medical records.Results: Of all patients who had spirometry performed, 15.8% showed airflow limitation (FEV1/FVC < 0.7. A variety of diseases were observed in patients with airflow limitation. Among all diseases, cardiovascular disease was the highest and gastrointestinal malignant disease had the second highest prevalence in patients with airflow limitation.Conclusion: COPD might be frequent in conditions of comorbidity in patients treated for various diseases. Attention should be paid to the possibility of co-existence of COPD and the influence of COPD on these patients.Keywords: airflow limitation, chronic obstructive pulmonary disease, comorbidity, spirometry, prevalence

  5. A case of cholestatic hepatitis associated with histologic features of acute cholangitis

    Directory of Open Access Journals (Sweden)

    Takeuchi H

    2011-11-01

    Full Text Available Hajime Takeuchi1, Toru Kaneko1, Toshikazu Otsuka1, Kumiko Tahara1, Tadashi Motoori2, Makoto Ohbu3, Masaya Oda4, Hiroaki Yokomori11Department of Internal Medicine; 2Division of Pathology, Kitasato Medical Center Hospital, Kitasato University, Saitama; 3Department of Pathology, School of Allied Health Sciences, Kitasato University, Sagamihara, Kanagawa; 4Department of Internal Medicine, Saitama Social Insurance Hospital, Saitama; 5Organized Center of Clinical Medicine, International University of Health and Welfare, Sanno Hospital, Tokyo, JapanAbstract: This report describes a case showing histologic features of acute cholangitis with an over-the-counter drug. A 48-year-old woman was diagnosed with general malaise and progressive jaundice. A thorough review of her medical history revealed that the patient had taken an over-the-counter drug, Pabron Gold®, which she had used previously, that may have caused liver injury. Laboratory investigations revealed jaundice and liver dysfunction. Endoscopic retrograde cholangiography detected no extrahepatic biliary duct dilatation or stones. Liver biopsy indicated acute cholangitis involving neutrophils and eosinophils. Electron microscopy revealed fragmented nuclei, indicating that the degenerative bile duct-related epithelial cells were in an apoptotic process.Keywords: liver injury, over-the-counter drug, histologic features, acute cholangitis, electron microscopy, Pabron Gold

  6. The Colonial and Transnational Production of "Suicide Squad at the Watchtower" and "Love and the Vow"

    Directory of Open Access Journals (Sweden)

    Naoki Watanabe

    2012-12-01

    Full Text Available This article places two Japan-Korea collaboration films produced during the Pacific War—"Suicide Squad at the Watchtower" (Bōrō no kesshitai, 1943 and "Love and the Vow" (Ai to chikai, 1945—within the broader colonial and transnational context of filmmaking. Specifically, it focuses on the relationship of these films to the careers of their co-directors, Imai Tadashi (1912–1991 and Ch’oe In-gyu (1911–1950?. At the same time, the article shows how cinematic and cultural conventions such as the bildungsroman and the “Victorian empire film,” which are more commonly associated with cultural production in the modern West, can, with appropriate adjustments, be fruitfully used to understand the power and entertainment value of these films. "Suicide Squad at the Watchtower" portrays a joint Japanese-Korean police squad controlling the border between Manchuria and Korea and its service to the Japanese empire; "Love and the Vow" is a story about a Korean orphan boy who, after interviewing the family of a kamikaze pilot, is inspired to become an imperial soldier himself. These two films were joint projects between Tōhō Film in Japan, where Imai was employed, and the Korean Motion Picture Production Corporation, the only film production company in colonial Korea (and the company into which all Korean film production companies had been absorbed during the war.

  7. Doxorubicin-resistant LoVo adenocarcinoma cells display resistance to apoptosis induction by some but not all inhibitors of ser/thr phosphatases 1 and 2A.

    Science.gov (United States)

    Sieder, S; Richter, E; Becker, K; Heins, R; Steinfelder, H J

    1999-06-15

    LoVo adenocarcinoma cells are fairly sensitive to cytostatic drugs, e.g. doxorubicin, but can develop drug resistance by expression of a P-glycoprotein-mediated MDR1 phenotype. LoVo cells respond with apoptosis to nanomolar concentrations of okadaic acid and micromolar concentrations of cantharidic acid. Interestingly, LoVoDx cells which had become about 10-fold less sensitive to doxorubicin by incubation in increasing concentrations of this cytostatic drug were also less sensitive to the toxicity of okadaic acid. Resistance to both agents was lost or significantly reduced by incubation in drug-free medium for about 4 months. On the other hand, LoVoDx cells did not lose responsiveness to the structurally different phosphatase inhibitor cantharidic acid but were about twofold more sensitive to the cytotoxic effect of this agent. Thus, MDR expression protects LoVo cells from the toxicity of phosphatase inhibitors that presumably are substrates of the P-glycoprotein, e.g. okadaic acid and its derivatives but not cantharidic acid, despite the fact that both agents are potent inducers of apoptotic cell death via ser/thr phosphatase inhibition.

  8. Significance of downregulation of renal organic cation transporter (SLC47A1 in cisplatin-induced proximal tubular injury

    Directory of Open Access Journals (Sweden)

    Mizuno T

    2015-07-01

    Full Text Available Tomohiro Mizuno,1–3 Waichi Sato,2,3 Kazuhiro Ishikawa,4 Yuki Terao,1 Kazuo Takahashi,2 Yukihiro Noda,5 Yukio Yuzawa,2 Tadashi Nagamatsu1 1Department of Analytical Pharmacology, Meijo University Faculty of Pharmacy, Nagoya, 2Department of Nephrology, School of Medicine, Fujita Health University, Toyoake, 3Department of Nephrology, Nagoya University School of Medicine, Nagoya, 4Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, Nagoya, 5Division of Clinical Sciences and Neuropsychopharmacology, Meijo University Faculty of Pharmacy, Nagoya, Japan Background/aim: To elucidate the mechanism responsible for developing acute kidney injury in patients with diabetes mellitus, we also evaluated the issue of whether advanced glycation endproducts (AGEs influence the expressions of multi antimicrobial extrusion protein (MATE1/SLC47A1 in tubular cells. Materials and methods: To detect changing expression of MATE1/SLC47A1 in dose- and time-dependent manners, human proximal tubular epithelial cells were incubated with AGE-aggregated-human serum albumin. As a function assay for MATE1/SLC47A1, human proximal tubular epithelial cells were incubated with cisplatin or carboplatin. Results: On incubation with AGEs, the expressions of MATE1/SLC47A1 were decreased in tubular cells. In addition, the toxicities of cisplatin were increased in tubular cells that had been pretreated with AGEs. However, the toxicities of carboplatin were smaller than that of cisplatin in proximal tubular epithelial cells. Conclusion: The expression of the MATE1/SLC47A1 is decreased by AGEs, which increases the risk for proximal tubular injury. Keywords: advanced glycation endproducts, cisplatin, SLC47A1, diabetes mellitus, acute kidney injury

  9. Tipepidine in adolescent patients with depression: a 4 week, open-label, preliminary study

    Directory of Open Access Journals (Sweden)

    Sasaki T

    2014-05-01

    Full Text Available Tsuyoshi Sasaki,1,2 Kenji Hashimoto,3 Masumi Tachibana,1 Tsutomu Kurata,1 Hiroshi Kimura,2 Hideki Komatsu,2 Masatomo Ishikawa,2 Tadashi Hasegawa,2 Akihiro Shiina,1 Tasuku Hashimoto,2 Nobuhisa Kanahara,4 Tetsuya Shiraishi,2 Masaomi Iyo1–41Department of Child Psychiatry, Chiba University Hospital, 2Department of Psychiatry, Chiba University Graduate School of Medicine, 3Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, 4Division of Medical Treatment and Rehabilitation, Chiba University Center for Forensic Mental Health, Inohana, Chiba, JapanDepression in children and adolescents is a common, recurrent, and debilitating condition associated with increased psychosocial, and medical morbidity and mortality.1The global prevalence of depression in children and adolescents is 1%–2% and 3%–8%, respectively.2 Depressive symptoms are also associated with significant functional impairment in school and the work place (often requiring legal interventions,1–5 and an increased risk for substance abuse and suicide.6–9 Clinical guidelines suggest the use of two selective serotonin reuptake inhibitors (SSRI, namely fluoxetine and escitalopram, both of which are effective with generally acceptable safety profiles in the treatment of adolescent depression.10 Additionally, combination treatment with an SSRI and psychotherapy, typically cognitive behavioral therapy (CBT, has shown benefit in this cohort.10 However, caution is warranted since antidepressants therapy in children and adolescents is associated with increased rates of suicidal ideation11–13 and adverse effects, characterized by excessive emotional arousal or behavioral activation.14 These results highlight the need for new therapies in adolescent patients with depression, particularly therapies with fewer side effects.View original paper by Brent and Maalouf.

  10. PREFACE: International Conference on High Pressure Science and Technology, Joint AIRAPT-22 & HPCJ-50

    Science.gov (United States)

    Viña, Luis; Tejedor, Carlos; Calleja, José M.

    2010-01-01

    The International Joint AIRAPT-22 & HPCJ-50 Conference was held in Odaiba, Tokyo, on 26-31 July 2009. About 480 scientists from 24 countries attended the conference and 464 papers, including 3 plenary lectures, 39 invited talks, and 156 oral presentations, were presented. It is my great pleasure to present this proceedings volume, which is based on the high quality scientific works presented at the conference. The International AIRAPT conference has been held every two years in various countries around the world since 1965, while High Pressure Conference of Japan (HPCJ) has been held annually since 1959 in various Japanese cities. Pressure is a fundamental parameter to control the property of matter. As a result, both AIRAPT and HPCJ have become highly multidisciplinary, and cover Physics, Chemistry, Materials Science, Earth and Planetary Sciences, Biosciences, Food Science, and Technology. Although each discipline has a unique target, they all have high-pressure research in common. This proceedings volume includes about 200 papers of state-of-the-art studies from numerous fields. I hope this proceedings volume provides excellent pieces of information in various fields to further advance high-pressure research. Conference logo Takehiko Yagi Conference Chairman Institute for Solid State Physics The University of Tokyo 7 December 2009 Conference photograph Participants at the conference venue, Tokyo International Exchange Center, Odaiba, Tokyo, Japan. Editor in Chief TAKEMURA Kenichi National Institute for Materials Science, Japan Editorial board Tadashi KONDO Osaka University, Japan Hitoshi MATSUKI The University of Tokushima, Japan Nobuyuki MATUBAYASI Kyoto University, Japan Yoshihisa MORI Okayama University of Science, Japan Osamu OHTAKA Osaka University, Japan Chihiro SEKINE Muroran Institute of Technology, Japan

  11. 恢复完整的身体——读铃木忠志《文化就是身体》

    Institute of Scientific and Technical Information of China (English)

    周夏奏

    2011-01-01

    在《文化就是身体》中,铃木忠志指出现代文明已经肢解了人类的身体,人类已愈发难以通过身体本能来认识彼此,遑论培养更深入密切的人际关系。在他看来,戏剧在很多方面都应该与现代文明背道而驰,除大量采用动物性能源、让观众透过可见之物“看见”不可见之物外,还应该容许、乃至倡导可能性。因此,他力图在戏剧的脉络下恢复完整的人类身体;以此为目标,其身体戏剧论述主要涉及三个方面:语言的身体性、身体与空间的关系以及“足的文法”。%In Culture is the Body, Suzuki Tadashi held that modernization has dismembered the human body. As a consequence, it is difficult for people to know each other through their bodies, let alone building better interpersonal relationship. Suzuki held that theatre should resist modernization in more than one ways, and proposed some methods to achieve the goal, such as heavily using animal-energy, letting the audience see the invisible through the visible, and admitting, or even better, encouraging possibility. In that way, Suzuki has been striving to restore the wholeness of human body in performance. His discussion of the physical theatre can be divided into three parts: the physicality of dialogue, the relations between body and space, and "the grammar of feet".

  12. Preliminary analysis of surface temperature anomalies that preceded the two major Emilia 2012 earthquakes (Italy

    Directory of Open Access Journals (Sweden)

    Kai Qin

    2012-10-01

    Full Text Available In the 1980's, from an analysis of satellite images, Russian scientists reported on a short-term thermal infrared radiation enhancement that occurred before some medium-to-large earthquakes in central Asia [Gorny et al. 1988]. Since then, many researchers have been studying earthquake thermal anomalies with satellite remote sensing data [Qiang et al. 1991, Tronin 1996, Tramutoli et al. 2001, Ouzounov and Freund 2004, Saraf and Choudhury 2004, Aliano et al. 2008, Blackett et al. 2011]. Recently, abnormal surface latent heat flux [Dey and Singh 2003, Cervone et al. 2005, Qin et al. 2009, Qin et al. 2011, Qin et al. 2012], outgoing long-wave radiation [Ouzounov et al. 2007] and microwave radiation [Takashi and Tadashi 2010] have also been shown to precede earthquakes. To investigate the possible physical mechanisms of such satellite thermal anomalies, some studies conducted a series of detecting experiments on rock loaded to fracturing [Wu et al. 2000, Freund 2002, Wu et al. 2002, Wu et al. 2006a, Wu et al. 2006b, Freund et al. 2007], and some hypotheses have been proposed. These have included: leaking of pore-gas, and hence the resulting greenhouse effect [Qiang et al. 1995]; activating and recombining of p-holes during rock deformation [Freund 2002]; release of latent heat due to near-surface air ionization [Pulinets et al. 2006], and stress-induced thermal effects due to friction and fluids [Wu and Liu 2009]. […] In this study, the long-term temperature data from both satellite and ground (with greater emphasis on the satellite data have been used to determine whether there were thermal anomalies associated with this Emilia 2012 seismic sequence. In particular, the next section will be dedicated to describing both the data and the method of analysis. In Section 3, we provide the more significant results, which we discuss in Section 4, together with the main conclusions. […

  13. Association of an overlap syndrome of autoimmune hepatitis and primary biliary cirrhosis with cytomegalovirus infection

    Directory of Open Access Journals (Sweden)

    Toyoda-Akui M

    2011-05-01

    Full Text Available Megumi Toyoda-Akui1,4, Hiroaki Yokomori1, Fumihiko Kaneko1,4, Yuki Shimizu1, Hajime Takeuchi1, Kumiko Tahara1, Hide Yoshida1, Hirobumi Kondo1, Tadashi Motoori2, Makoto Ohbu3, Masaya Oda5, Toshifumi Hibi61Department of Internal Medicine, 2Division of Pathology, Kitasato Medical Center Hospital, Kitasato University, Saitama; 3Department of Pathology, School of Allied Health Sciences, Kitasato University, Sagamihara, Kanagawa; 4Department of Internal Medicine, Saitama Social Insurance Hospital, Saitama; 5Organized Center of Clinical Medicine, International University of Health and Welfare, Tokyo; 6Division of Gastroenterology, Department of Internal Medicine, School of Medicine, Keio University, Tokyo, JapanAbstract: A 63-year-old woman, who presented with severe jaundice and elevated serum conjugated bilirubin level, denied alcohol and drug use and showed no evidence of viral hepatitis. Based on clinical and laboratory features, she was diagnosed with autoimmune hepatitis with primary biliary cirrhosis. Hematological and immunochemical assays, radiographic imaging, clinical examination, and liver biopsy were conducted. Laboratory results were the following: negative for fluorescence antinuclear antibody, negative for antismooth muscle antibodies but positive for antinuclear antibody (enzyme-linked immunosorbent assay and antimitochondrial M2 antibody, high titers of serum globulin, and positive for cytomegalovirus IgM. Liver biopsy showed submassive lobular necrosis, inflammation with broad areas of parenchymal collapse, and chronic nonsuppurative destructive cholangitis. The patient responded well to corticosteroid therapy. This case might illustrate an association between cytomegalovirus infection and the occurrence of autoimmune hepatitis.Keywords: autoimmune hepatitis, fluorescence antinuclear antibody, enzyme linked immuno sorbent assay, primary biliary cirrhosis, cytomegalovirus infection

  14. Tumor-promoting phorbol ester transiently down-modulates the p53 level and blocks the cell cycle

    DEFF Research Database (Denmark)

    Skouv, J; Jensen, P O; Forchhammer, J

    1994-01-01

    Activation of the protein kinase C signaling pathway by tumor-promoting phorbol esters, such as 4 beta-phorbol 12-myristate 13-acetate (PMA), induced a decrease in the level of p53 mRNA in several serum-starved human cell lines. Also, the tumor-promoting phosphatase inhibitor okadaic acid induced...... rate or the p53 mRNA stability. The protein synthesis inhibitor cycloheximide completely abolished the PMA-induced down-modulation of the p53 mRNA, suggesting that a short-lived protein was involved in the down-modulation. Flow cytometric cell cycle analysis showed that the phorbol ester treatment...

  15. Asymmetric dark matter in braneworld cosmology

    Energy Technology Data Exchange (ETDEWEB)

    Meehan, Michael T.; Whittingham, Ian B., E-mail: Michael.Meehan@my.jcu.edu.au, E-mail: Ian.Whittingham@jcu.edu.au [School of Engineering and Physical Sciences, James Cook University, Townsville, 4811 Australia (Australia)

    2014-06-01

    We investigate the effect of a braneworld expansion era on the relic density of asymmetric dark matter. We find that the enhanced expansion rate in the early universe predicted by the Randall-Sundrum II (RSII) model leads to earlier particle freeze-out and an enhanced relic density. This effect has been observed previously by Okada and Seto (2004) for symmetric dark matter models and here we extend their results to the case of asymmetric dark matter. We also discuss the enhanced asymmetric annihilation rate in the braneworld scenario and its implications for indirect detection experiments.

  16. Stemcell Information: SKIP000517 [SKIP Stemcell Database[Archive

    Lifescience Database Archive (English)

    Full Text Available ... Yohei Okada 岡田 洋平 Department of Physiology, Keio University School of Medicine 慶應義塾大学 医学部... 生理学教室 Department of Physiology, Keio University School of Medicine 慶應義塾大学 医学部 生理学教室 Hideyuki Okan...o 岡野 栄之 Information Only Department of Physiology, Keio University School of Medicine 慶應義塾大学 医学部 生理学教室 ...

  17. Stemcell Information: SKIP000516 [SKIP Stemcell Database[Archive

    Lifescience Database Archive (English)

    Full Text Available ... Yohei Okada 岡田 洋平 Department of Physiology, Keio University School of Medicine 慶應義塾大学 医学部... 生理学教室 Department of Physiology, Keio University School of Medicine 慶應義塾大学 医学部 生理学教室 Hideyuki Oka...no 岡野 栄之 Information Only Department of Physiology, Keio University School of Medicine 慶應義塾大学 医学部 生理学教室 ...

  18. Stemcell Information: SKIP000518 [SKIP Stemcell Database[Archive

    Lifescience Database Archive (English)

    Full Text Available ... Yohei Okada 岡田 洋平 Department of Physiology, Keio University School of Medicine 慶應義塾大学 医学部... 生理学教室 Department of Physiology, Keio University School of Medicine 慶應義塾大学 医学部 生理学教室 Hideyuki O...kano 岡野 栄之 Information Only Department of Physiology, Keio University School of Medicine 慶應義塾大学 医学部 生理学教室 ...

  19. Stemcell Information: SKIP000520 [SKIP Stemcell Database[Archive

    Lifescience Database Archive (English)

    Full Text Available ... Yohei Okada 岡田 洋平 Department of Physiology, Keio University School of Medicine 慶應義塾大学 医学部... 生理学教室 Department of Physiology, Keio University School of Medicine 慶應義塾大学 医学部 生理学教室 Hideyuki O...kano 岡野 栄之 Information Only Department of Physiology, Keio University School of Medicine 慶應義塾大学 医学部 生理学教室 ...

  20. Stemcell Information: SKIP000519 [SKIP Stemcell Database[Archive

    Lifescience Database Archive (English)

    Full Text Available ... Yohei Okada 岡田 洋平 Department of Physiology, Keio University School of Medicine 慶應義塾大学 医学部... 生理学教室 Department of Physiology, Keio University School of Medicine 慶應義塾大学 医学部 生理学教室 Hideyuki O...kano 岡野 栄之 Information Only Department of Physiology, Keio University School of Medicine 慶應義塾大学 医学部 生理学教室 ...

  1. Stemcell Information: SKIP000515 [SKIP Stemcell Database[Archive

    Lifescience Database Archive (English)

    Full Text Available ... Yohei Okada 岡田 洋平 Department of Physiology, Keio University School of Medicine 慶應義塾大学 医学部... 生理学教室 Department of Physiology, Keio University School of Medicine 慶應義塾大学 医学部 生理学教室 Hideyuki Okan...o 岡野 栄之 Information Only Department of Physiology, Keio University School of Medicine 慶應義塾大学 医学部 生理学教室 ...

  2. The Effects of Optical Feedback on Polarization of Vertical Cavity Surface Emitting Lasers

    Science.gov (United States)

    1993-12-01

    most puzzling item is the size of the circular components. There is no theoretical reason or experimental precedent for circular polarized light from...Mori, K., T. Asaka, H. lwano, M. Ogura, S. Fujii, T. Okada, and S. Mukai. "Effect, of Cavity Size on Lasing Characteristics of a Distributed Bragg...Hill, NC 27514 52 REPORT DOCUMENTATION PAGE [ oI Punk fftVmog &,Fw Wo ins :omectoom of ,nmonmator -% W..at" to sageq n, .vW a"? ’- A tei t,. flo to" M

  3. Targeting Neuroendocrine Differentiation for Prostate Cancer Radiosensitization

    Science.gov (United States)

    2014-10-01

    Shibatohge, M., Kariya, K., Liao, Y., Hu, C.D., Watari , Y., Goshima, M., Shima, F., and Kataoka, T. Identification of PLC210, a C. elegans homolog of...Hokaido University Medical Library Series, 37, 141-146 (1998). 14. Watari , Y., Kariya, K., Shibatohge, M., Liao, Y., Hu, C.D., Goshima, M., Tamada...mediated adhesion of T cells. J. Immunol., 163, 6209-6216 (1999). 18. Liao, Y., Kariya, K., Hu, C.D., Shibatohge, M., Goshima, M., Okada, T., Watari , Y

  4. The Electron/Muon Specific Two Higgs Doublet Model at e+ e- Colliders

    OpenAIRE

    Johansen, Aria R.; Sher, Marc

    2015-01-01

    Recently, Kajiyama, Okada and Yagyu (KOY) proposed an electron/muon specific two Higgs doublet model. In this model, an S3 symmetry suppresses flavor changing neutral currents instead of a Z2 symmetry. In the "Type I" version of the model, the heavy Higgs bosons have a greatly enhanced coupling to electrons and muons. KOY studied the phenomenology of the heavy Higgs bosons at the LHC. In this paper, the phenomenology at electron-positron colliders is studied. For the heavy Higgs mass range be...

  5. The MAP kinase pathway is required for entry into mitosis and cell survival.

    Science.gov (United States)

    Liu, Xiaoqi; Yan, Shi; Zhou, Tianhua; Terada, Yasuhiko; Erikson, Raymond L

    2004-01-22

    In this communication, we examined the role of the MAP kinase pathway in the G2/M phase of the cell cycle. Activation of the Plk1 and MAP kinase pathways was initially evaluated in FT210 cells, which arrest at G2 phase at the restrictive temperature (39 degrees C), due to a mutation in the cdc2 gene. Previous studies had shown that these cells enter mitosis at the nonpermissive temperature upon incubation with okadaic acid, a protein phosphatase 1 and 2A inhibitor. We show that treatment of FT210 cells at 39 degrees C with okadaic acid activated Plk1, as shown by hyperphosphorylation and elevated protein kinase activity, and also induced activation of the MAP kinase pathway. The specific Mek inhibitor PD98059 antagonized the okadaic acid-induced activation of both Plk1 and MAP kinases. This suggests that activation of the MAP kinase pathway may contribute to the okadaic acid-induced activation of Plk1 in FT210 cells at 39 degrees C. We also found that PD98059 strongly attenuated progression of HeLa cells through mitosis, and active Mek colocalizes with Plk1 at mitotic structures. To study the potential function of the MAP kinase pathway during mitosis, RNAi was used to specifically deplete five members of this pathway (Raf1, Mek1/2, Erk1/2). Each of these five protein kinases is required for cell proliferation and survival, and depletion of any of these proteins eventually leads to apoptosis. Treatment with Mek inhibitors also inhibited cell proliferation and caused apoptosis. A dramatic increase of Plk1 activities and a moderate increase of Cdc2 activities in Raf1-depleted cells indicate that Raf1-depleted cells arrest in the late G2 or M phase. Mek1 and Erk1 depletion also caused cell cycle arrest at G2, suggesting that these enzymes are required for the G2/M transition, whereas the loss of Mek2 or Erk2 caused arrest at G1.

  6. Monitoring and inversion on land subsidence over mining area with InSAR technique

    Science.gov (United States)

    Wang, Y.; Zhang, Q.; Zhao, C.; Lu, Zhiming; Ding, X.

    2011-01-01

    The Wulanmulun town, located in Inner Mongolia, is one of the main mining areas of Shendong Company such as Shangwan coal mine and Bulianta coal mine, which has been suffering serious mine collapse with the underground mine withdrawal. We use ALOS/PALSAR data to extract land deformation under these regions, in which Small Baseline Subsets (SBAS) method was applied. Then we compared InSAR results with the underground mining activities, and found high correlations between them. Lastly we applied Distributed Dislocation (Okada) model to invert the mine collapse mechanism. ?? 2011 Copyright Society of Photo-Optical Instrumentation Engineers (SPIE).

  7. Short term memory bowing effect is consistent with presentation rate dependent decay

    OpenAIRE

    Tarnow, Eugen

    2010-01-01

    I reanalyze the free recall data of Murdock, J Exp Psychol 64(5):482–488 (1962) and Murdock and Okada, J Verbal Learn and Verbal Behav 86:263–267 (1970) which show the famous bowing effect in which initial and recent items are recalled better than intermediate items (primacy and recency effects). Recent item recall probabilities follow a logarithmic decay with time of recall consistent with the tagging/retagging theory. The slope of the decay increases with increasing presentation rate. The i...

  8. The first determination of DNA sequence of a specific gene.

    Science.gov (United States)

    Inouye, Masayori

    2016-05-10

    How and when the first DNA sequence of a gene was determined? In 1977, F. Sanger came up with an innovative technology to sequence DNA by using chain terminators, and determined the entire DNA sequence of the 5375-base genome of bacteriophage φX 174 (Sanger et al., 1977). While this Sanger's achievement has been recognized as the first DNA sequencing of genes, we had determined DNA sequence of a gene, albeit a partial sequence, 11 years before the Sanger's DNA sequence (Okada et al., 1966).

  9. Heterogeneous Solvatochromism of Fluorescent DNA-Stabilized Silver Clusters Precludes Use of Simple Onsager-Based Stokes Shift Models.

    Science.gov (United States)

    Copp, Stacy M; Faris, Alexis; Swasey, Steven M; Gwinn, Elisabeth G

    2016-02-18

    The diverse optical and chemical properties of DNA-stabilized silver clusters (AgN-DNAs) have challenged the development of a common model for these sequence-tunable fluorophores. Although correlations between cluster geometry and fluorescence color have begun to shed light on how the optical properties of AgN-DNAs are selected, the exact mechanisms responsible for fluorescence remain unknown. To explore these mechanisms, we study four distinct purified AgN-DNAs in ethanol-water and methanol-water mixtures and find that the solvatochromic behavior of AgN-DNAs varies widely among different cluster species and differs markedly from prior results on impure material. Placing AgN-DNAs within the context of standard Lippert-Mataga solvatochromism models based on the Onsager reaction field, we show that such nonspecific solvent models are not universally applicable to AgN-DNAs. Instead, alcohol-induced solvatochromism of AgN-DNAs may be governed by changes in hydration of the DNA template, with spectral shifts resulting from cluster shape changes and/or dielectric changes in the local vicinity of the cluster.

  10. Donor-acceptor substituted phenylethynyltriphenylenes – excited state intramolecular charge transfer, solvatochromic absorption and fluorescence emission

    Directory of Open Access Journals (Sweden)

    Ritesh Nandy

    2010-10-01

    Full Text Available Several 2-(phenylethynyltriphenylene derivatives bearing electron donor and acceptor substituents on the phenyl rings have been synthesized. The absorption and fluorescence emission properties of these molecules have been studied in solvents of different polarity. For a given derivative, solvent polarity had minimal effect on the absorption maxima. However, for a given solvent the absorption maxima red shifted with increasing conjugation of the substituent. The fluorescence emission of these derivatives was very sensitive to solvent polarity. In the presence of strongly electron withdrawing (–CN and strongly electron donating (–NMe2 substituents large Stokes shifts (up to 130 nm, 7828 cm−1 were observed in DMSO. In the presence of carbonyl substituents (–COMe and –COPh, the largest Stokes shift (140 nm, 8163 cm−1 was observed in ethanol. Linear correlation was observed for the Stokes shifts in a Lippert–Mataga plot. Linear correlation of Stokes shift was also observed with ET(30 scale for protic and aprotic solvents but with different slopes. These results indicate that the fluorescence emission arises from excited state intramolecular charge transfer in these molecules where the triphenylene chromophore acts either as a donor or as an acceptor depending upon the nature of the substituent on the phenyl ring. HOMO–LUMO energy gaps have been estimated from the electrochemical and spectral data for these derivatives. The HOMO and LUMO surfaces were obtained from DFT calculations.

  11. Highly Soluble Monoamino-Substituted Perylene Tetracarboxylic Dianhydrides: Synthesis, Optical and Electrochemical Properties

    Directory of Open Access Journals (Sweden)

    Kew-Yu Chen

    2014-12-01

    Full Text Available Three dialkylamino-substituted perylene tetracarboxylic dianhydrides with different n-alkyl chain lengths (n = 6, 12 or 18, 1a–1c, were synthesized under mild conditions in high yields and were characterized by 1H NMR, 13C NMR and high resolution mass spectroscopy. Their optical and electrochemical properties were measured using UV-Vis and emission spectroscopic techniques, as well as cyclic voltammetry (CV. This is the first time that the structures and the properties of monoamino-substituted perylene tetracarboxylic dianhydrides have been reported. These molecules show a deep green color in both solution and the solid state and are soluble in most organic solvents. They all show a unique charge transfer emission in the near-infrared region, and the associated peaks exhibit solvatochromism. The dipole moments of the compounds have been estimated using the Lippert-Mataga equation, and upon excitation, they show slightly larger dipole moment changes than those of corresponding perylene diimides, 2a–2c. Additionally, Compounds 1a–1c undergo two quasi-reversible one-electron oxidations and two quasi-reversible one-electron reductions in dichloromethane at modest potentials. Complementary density functional theory calculations performed on these chromophores are reported in order to gain more insight into their molecular structures and optical properties.

  12. Green Perylene Bisimide Dyes: Synthesis, Photophysical and Electrochemical Properties

    Directory of Open Access Journals (Sweden)

    Che-Wei Chang

    2014-07-01

    Full Text Available Three asymmetric amino-substituted perylene bisimide dyes with different n-alkyl chain lengths (n = 6, 12, or 18, 1-(N,N-dialkylaminoperylene bisimides (1a–1c, were synthesized under mild condition in high yields and were characterized by 1H NMR, 13C NMR (nuclear magnetic resonance, HRMS (High Resolution Mass Spectrometer, UV-Vis and fluorescence spectra, as well as cyclic voltammetry (CV. These molecules show intense green color in both solution and solid state and are highly soluble in dichloromethane and even in nonpolar solvents, such as hexane. The shapes of the absorption spectra of 1a–1c in solid state and in solution were found to be virtually the same, indicating that the long alkyl chains could efficiently prevent aggregation. They exhibit a unique charge transfer emission in the near-infrared region, of which the peak wavelengths show strong solvatochromism. The dipole moments of the compounds have been estimated using the Lippert-Mataga equation, and upon excitation, they show larger dipole moment changes than that of 1-aminoperylene bisimide (2. Furthermore, all of the compounds exhibit two quasi-reversible one-electron oxidations and two quasi-reversible one-electron reductions in dichloromethane at modest potentials. Complementary density functional theory (DFT calculations performed on these dyes are reported in order to rationalize their molecular structures and electronic properties.

  13. 1,7-Bis-(N,N-dialkylaminoperylene Bisimides: Facile Synthesis and Characterization as Near-Infrared Fluorescent Dyes

    Directory of Open Access Journals (Sweden)

    Kew-Yu Chen

    2014-11-01

    Full Text Available Three symmetric alkylamino-substituted perylene bisimides with different n-alkyl chain lengths (n = 6, 12, or 18, 1,7-bis-(N,N-dialkylaminoperylene bisimides (1a–1c, were synthesized under mild condition and were characterized by 1H NMR, 13C NMR and high resolution mass spectroscopy. Their optical and electrochemical properties were measured using UV-Vis and emission spectroscopic techniques as well as cyclic voltammetry (CV. These compounds show deep green color in both solution and solid state, and are highly soluble in dichloromethane and even in nonpolar solvents such as hexane. The shapes of the absorption spectra of 1a–1c in the solution and solid state were found to be almost the same, indicating that the long alkyl chains could efficiently prevent intermolecular contact and aggregation. They show a unique charge transfer emission in the near-infrared region, of which the peak wavelengths exhibit strong solvatochromism. The dipole moments of the molecules have been estimated using the Lippert–Mataga equation, and upon excitation, they show larger dipole moment changes than that of 1,7-diaminoperylene bisimide (2. Moreover, all the dyes exhibit two irreversible one-electron oxidations and two quasi-reversible one-electron reductions in dichloromethane at modest potentials. Complementary density functional theory calculations performed on these chromophores are reported in order to rationalize their electronic structure and optical properties.

  14. Structural and photophysical properties of alkylamino substituted 2-arylidene and 2,5-diarylidene cyclopentanone dyes

    Science.gov (United States)

    Zoto, Christopher A.; Ucak-Astarlioglu, Mine G.; MacDonald, John C.; Connors, Robert E.

    2016-05-01

    A series of alkylamino substituted 2-arylidene and 2,5-diarylidene cyclopentanone compounds were synthesized. Spectroscopic and photophysical properties of these compounds have been measured in a variety of solvents. Absorption and fluorescence maxima have been correlated with the Empirical Scale of Solvent Polarity (ET(30)). Theoretical TD-DFT spectral calculations and Lippert-Mataga analysis support the internal charge transfer (ICT) nature of the S0 → S1 excitation for these compounds, with higher degrees of ICT depicted for the alkylamino substituted 2,5-diarylidene cyclopentanones. Photophysical properties consisted of measuring the fluorescence quantum yields (Φf) and lifetimes (τf) in a variety of solvents. Radiative and nonradiative decay constants have been determined from the Φf and τf data. Variation with solvent in the nonradiative rate of decay is interpreted in terms of a competition between internal conversion and intersystem crossing. Lastly, two compounds presented have been shown to undergo excited state protonation in glacial acetic acid.

  15. Synthesis and fluorescent properties of poly(arylpyrazoline)'s for organic-electronics

    Science.gov (United States)

    Vandana, T.; Ramkumar, V.; Kannan, P.

    2016-08-01

    The present work focuses on the synthesis and characterization of poly(arylchalcone)'s (PCH I-IV) by reacting acetone with various dialdehydes for the first time at below ambient temperature followed by cyclization with phenylhydrazinehydrochloride to yield luminescent poly(arylpyrazoline)'s (PPY I-IV). The synthesized polymers were characterized by standard techniques such as, GPC, SEM, TGA, FT-IR, 1H NMR, UV-Vis absorption and fluorescence spectroscopy, and electrochemical studies by cyclic voltammetry analyses. The Pyrazoline group hooked with different aryl donors such as benzene, thiophene, carbazole, triphenylamine, thus results a series of blue and green emitting materials. The obtained optical bandgap energy of the polymers (PPY I-IV) were 2.53, 3.41, 3.07, 3.10 eV respectively, suggest that all the polymers belongs to semiconducting category. The solvent effect of polymers was thoroughly studied and explained by Lippert-Mataga equation. The polymers I & IV display large degree of intra-molecular charge transfer in excited state evidenced from solvatochromic shift on the emission spectra. The obtained results demonstrate that they are promising materials for organic electronics applications.

  16. Estimation of ground and excited-state dipole moments of 1, 2-diazines by solvatochromic method and quantum-chemical calculation

    DEFF Research Database (Denmark)

    Manohara, S.R.; Kumar, V. Udaya; Shivakumaraiah;

    2013-01-01

    Using the theory of solvatochromism, the difference in the excited-state (μe) and ground-state (μg) dipole moments was determined from Lippert–Mataga, Bakhshiev, Kawski–Chamma–Viallet, and McRae equations for three 1,2-diazines (pyrrolo-pyridazine derivatives). All of these equations are based...... on the variation of Stokes shift with solvent's relative permittivity and refractive index. Further, the change in dipole moment value (Δμ) was also calculated using the variation of Stokes shift with the molecular-microscopic empirical solvent polarity parameter. Theoretical μg values were evaluated by quantum...... chemical calculations using the DFT method by adopting B3LYP/6-31G* level of theory (Gaussian 03) and using the AM1 method (Chem3D Ultra 8.0). It was observed that, dipole moments of diazines in the excited-state (μe) were greater than the corresponding ground-state values (μg), indicating a substantial...

  17. Quinazolinone derivative: Model compound for determination of dipole moment, solvatochromism and metal ion sensing

    Science.gov (United States)

    Al-Sehemi, Abdullah G.; Pannipara, Mehboobali; Kalam, Abul

    2017-01-01

    A dihydroquinazolinone derivative 2-(2,4-Dimethoxy-phenyl)-2,3-dihydro-1H-quinazolin-4-one (1) was synthesized and characterized by 1H NMR, 13C NMR and FT-IR and its spectral, photophysical, intramolecular charge transfer characteristics were studied by absorption and emission spectroscopy. The compound exhibits significant changes in their photophysical properties depending on the solvent polarity. The observed bathochromic emission band and difference in Stokes shift on changing the polarity of the solvents clearly demonstrate the highly polar character of the excited state, which is also supported by the enhancement of dipole moment of the molecule upon photoexcitation. Solvatochromic shift methods based on Lippert-Mataga, Bakhshiev-Kawski and Reichardt's correlations were applied to calculate the ground, excited and change in dipole moments. The effect of solute-solvent interactions on compound 1 was studied using multi-parameter solvent polarity scales proposed by Kamlet-Taft and Catalan. The interactions of various metal ions on compound 1 were also studied using steady state fluorescence measurements. The emission profile reveals that it acts as on-off type fluorescent chemosensor for selective and sensitive detection of Hg2 + ions. Complexation stoichiometry and mechanism of quenching were determined from Benesi-Hildebrand and Stern-Volmer plot.

  18. UV-Vis spectroscopy and density functional study of solvent effect on the charge transfer band of the n → σ* complexes of 2-Methylpyridine and 2-Chloropyridine with molecular iodine

    Science.gov (United States)

    Gogoi, Pallavi; Mohan, Uttam; Borpuzari, Manash Protim; Boruah, Abhijit; Baruah, Surjya Kumar

    2017-03-01

    UV-Vis spectroscopy has established that Pyridine substitutes form n→σ* charge transfer (CT) complexes with molecular Iodine. This study is a combined approach of purely experimental UV-Vis spectroscopy, Multiple linear regression theory and Computational chemistry to analyze the effect of solvent upon the charge transfer band of 2-Methylpyridine-I2 and 2-Chloropyridine-I2 complexes. Regression analysis verifies the dependence of the CT band upon different solvent parameters. Dielectric constant and refractive index are considered among the bulk solvent parameters and Hansen, Kamlet and Catalan parameters are taken into consideration at the molecular level. Density Functional Theory results explain well the blue shift of the CT bands in polar medium as an outcome of stronger donor acceptor interaction. A logarithmic relation between the bond length of the bridging atoms of the donor and the acceptor with the dielectric constant of the medium is established. Tauc plot and TDDFT study indicates a non-vertical electronic transition in the complexes. Buckingham and Lippert Mataga equations are applied to check the Polarizability effect on the CT band.

  19. Theoretical Study on Electron Transfer Matrix Element in Oxidation of α—Amino Carbon—Centered Radical by O2

    Institute of Scientific and Technical Information of China (English)

    刘继凤; 朱权; 李象远; 杨胜勇

    2002-01-01

    As a successive work of our previous paper,1the electron transfer matrix element(Vrp)in the oxidation of the simplified model molecule of α-amino carbon-centered radical by O2 has been investigated with ab initio calculation at the level of UHF/6-31 G**.Based on the optimized geometries of the reactgant and the ion-pair complex obtained previously,the reaction heat and the iuner reorganization energy have been obtained by constructing the potential energy curves of reactant and product states considering the solvent effect with the conductor-like screening model(COSMO).The solvent reorganization energy has been estimated using Lippert-Mataga relationship.The calculated results show that the value of Vrp is several times larger than that of RT,which means that the model reaction is an adiabatic one.Theoretical investigation indicates that the solvent effect on the direct electron transfer (ET) process of oxidation of α-amino carbon-centered radical by oxygen is remarkable.

  20. Solvent effects on the photophysical properties of poly[1,4-dihydroxyanthraquinoneimine-1,3-bis(phenylene-ester-methylene)tetramethyldisiloxane].

    Science.gov (United States)

    Dorneanu, Petronela Pascariu; Homocianu, Mihaela; Tigoianu, Ionut Radu; Airinei, Anton; Zaltariov, Mirela; Cazacu, Maria

    2015-01-05

    Absorption and fluorescence spectra of a polyquinoneimine, PQI, built on 1,4-dihydroxyanthraquinone and a siloxane diamine, 1,3-bis(amino-phenylene-ester-methylene)tetramethyldisiloxane, have been investigated in solvents of different polarities. The effect of solvents on the spectral properties was investigated using Lippert-Mataga and Bakhshiev polarity functions and Catalán's multiple linear regression approach. Absorption and fluorescence spectra in studied solvents exhibit hypsochromic and bathochromic shifts, respectively. The polarity of the solvent was the main parameter which changes the spectral properties of PQI. Also, the binary mixtures of chloroform with methanol and dimethyl sulfoxide were used to analyze the intermolecular interactions and preferential solvation. The preferential solvation parameters (local mole fraction (X₂(L)), excess function (δs₂) and preferential solvation constant (KPS)) were calculated from spectral data and discussed as a function of cosolvent content. The values of quantum yield, decreased linearly with increasing solvent polarity (for non-polar and polar solvents).

  1. Theoretical Study on Electron Transfer Matrix Element in Oxidation of a-Amino Carbon-Centered Radical by O2

    Institute of Scientific and Technical Information of China (English)

    LIU,Ji-Feng(刘继凤); ZHU,Quan(朱权); LI,Xiang-Yuan(李象远); YANG,Sheng-Yong(杨胜勇)

    2002-01-01

    As a successive work of our previous paper, 1 the electron transfer matrix element ( Vrp) in the oxidation of the simplified model molecule of α-amino carbon-centered radical by O2 has been investigated with ab initio calculation at the level of UHF/6-31 + + G * * . Based on the optimized geometries of the reactant and the ion-pair complex obtained previously, the reaction heat and the inner reorganization energy have been obrained by constructing the potential energy curves of reactant and product states considering the solvent effect with the conductor-like screening model (COSMO). The solvent reorganization energy has been estimated using Lippert-Mataga relationship. The calculated results show that the value of Vrp is several times larger than that of RT, which means that the model reaction is an adiabatic one. Theoretical investigation indicates that the solvent effect on the direct electron transfer (ET) process of oxidation of α-amino carbon-centered radical by oxygen is remarkable.

  2. Synthesis, spectral behaviour and photophysics of donor-acceptor kind of chalcones: Excited state intramolecular charge transfer and fluorescence quenching studies

    Science.gov (United States)

    Pannipara, Mehboobali; Asiri, Abdullah M.; Alamry, Khalid A.; Arshad, Muhammad N.; El-Daly, Samy A.

    2015-02-01

    The spectral and photophysical properties of two chalcones containing electron donating and accepting groups with intramolecular charge transfer characteristics were synthesized and characterized by 1H NMR, 13C NMR and X-ray crystallography. Both compounds show very strong solvent polarity dependent changes in their photophysical characteristics, namely, remarkable red shift in the emission spectra with increasing solvent polarity, large change in Stokes shift, significant reduction in the fluorescence quantum yield; indicating that the fluorescence states of these compounds are of intramolecular charge transfer (ICT) character. The solvent effect on the photophysical parameters such as singlet absorption, molar absorptivity, oscillator strength, dipole moment, fluorescence spectra, and fluorescence quantum yield of both compounds have been investigated comprehensively. For both dyes, Lippert-Mataga and Reichardt's correlations were used to estimate the difference between the excited and ground state dipole moments (Δμ). The interactions of dyes with colloidal silver nanoparticles (Ag NPs) were also studied in ethanol using steady state fluorescence quenching measurements. The fluorescence quenching data reveal that dynamic quenching and energy transfer play a major role in the fluorescence quenching of dyes by Ag NPs.

  3. O problema de caminho mínimo com incertezas e restrições de tempo

    Directory of Open Access Journals (Sweden)

    Fábio Hernandes

    2009-08-01

    Full Text Available O problema de caminho mínimo em grafos com parâmetros incertos é um importante problema da programação matemática, visto que possui aplicações nas mais diversas áreas da Computação e da Engenharia, como: redes de computadores, telecomunicações, transportes, manufaturas, dentre outros. Porém, devido à sua alta complexidade computacional, poucos são os algoritmos existentes na literatura. Neste trabalho é proposto um algoritmo, baseado no algoritmo de Okada & Soper, que utiliza dois parâmetros incertos nos arcos, custo e tempo, com restrições de tempo nos nós. As incertezas são abordadas utilizando a teoria dos conjuntos fuzzy.The shortest path problem in graphs with uncertainties in the parameters is an important problem in the mathematical programming, since it has a wide range of applications in different areas of Computation and Engineering, such as: computer networks, telecommunications, transportation, manufacturing, etc. However, due to its high computational complexity, there are few algorithms in the literature. In this paper is proposed an algorithm, based on Okada and Soper algorithm, which uses two uncertainty parameters, cost and time, with time restrictions in the nodes. The uncertainties are discussed using the fuzzy set theory.

  4. Experimental Basis for the High Oral Toxicity of Dinophysistoxin 1: A Comparative Study of DSP

    Directory of Open Access Journals (Sweden)

    Diego A. Fernández

    2014-01-01

    Full Text Available Okadaic acid (OA and its analogues, dinophysistoxin 1 (DTX1 and dinophysistoxin 2 (DTX2, are lipophilic and heat-stable marine toxins produced by dinoflagellates, which can accumulate in filter-feeding bivalves. These toxins cause diarrheic shellfish poisoning (DSP in humans shortly after the ingestion of contaminated seafood. Studies carried out in mice indicated that DSP poisonous are toxic towards experimental animals with a lethal oral dose 2–10 times higher than the intraperitoneal (i.p. lethal dose. The focus of this work was to study the absorption of OA, DTX1 and DTX2 through the human gut barrier using differentiated Caco-2 cells. Furthermore, we compared cytotoxicity parameters. Our data revealed that cellular viability was not compromised by toxin concentrations up to 1 μM for 72 h. Okadaic acid and DTX2 induced no significant damage; nevertheless, DTX1 was able to disrupt the integrity of Caco-2 monolayers at concentrations above 50 nM. In addition, confocal microscopy imaging confirmed that the tight-junction protein, occludin, was affected by DTX1. Permeability assays revealed that only DTX1 was able to significantly cross the intestinal epithelium at concentrations above 100 nM. These data suggest a higher oral toxicity of DTX1 compared to OA and DTX2.

  5. Experimental basis for the high oral toxicity of dinophysistoxin 1: a comparative study of DSP.

    Science.gov (United States)

    Fernández, Diego A; Louzao, M Carmen; Fraga, María; Vilariño, Natalia; Vieytes, Mercedes R; Botana, Luis M

    2014-01-03

    Okadaic acid (OA) and its analogues, dinophysistoxin 1 (DTX1) and dinophysistoxin 2 (DTX2), are lipophilic and heat-stable marine toxins produced by dinoflagellates, which can accumulate in filter-feeding bivalves. These toxins cause diarrheic shellfish poisoning (DSP) in humans shortly after the ingestion of contaminated seafood. Studies carried out in mice indicated that DSP poisonous are toxic towards experimental animals with a lethal oral dose 2-10 times higher than the intraperitoneal (i.p.) lethal dose. The focus of this work was to study the absorption of OA, DTX1 and DTX2 through the human gut barrier using differentiated Caco-2 cells. Furthermore, we compared cytotoxicity parameters. Our data revealed that cellular viability was not compromised by toxin concentrations up to 1 μM for 72 h. Okadaic acid and DTX2 induced no significant damage; nevertheless, DTX1 was able to disrupt the integrity of Caco-2 monolayers at concentrations above 50 nM. In addition, confocal microscopy imaging confirmed that the tight-junction protein, occludin, was affected by DTX1. Permeability assays revealed that only DTX1 was able to significantly cross the intestinal epithelium at concentrations above 100 nM. These data suggest a higher oral toxicity of DTX1 compared to OA and DTX2.

  6. Carcinogenic Aspects of Protein Phosphatase 1 and 2A Inhibitors

    Science.gov (United States)

    Fujiki, Hirota; Suganuma, Masami

    Okadaic acid is functionally a potent tumor promoter working through inhibition of protein phosphatases 1 and 2A (PP1 and PP2A), resulting in sustained phosphorylation of proteins in cells. The mechanism of tumor promotion with oka-daic acid is thus completely different from that of the classic tumor promoter phorbol ester. Other potent inhibitors of PP1 and PP2A - such as dinophysistoxin-1, calyculins A-H, microcystin-LR and its derivatives, and nodularin - were isolated from marine organisms, and their structural features including the crystal structure of the PP1-inhibitor complex, tumor promoting activities, and biochemical and biological effects, are here reviewed. The compounds induced tumor promoting activity in three different organs, including mouse skin, rat glandular stomach and rat liver, initiated with three different carcinogens. The results indicate that inhibition of PP1 and PP2A is a general mechanism of tumor promotion applicable to various organs. This study supports the concept of endogenous tumor promoters in human cancer development.

  7. Crystal structures of spinel-type Na2MoO4 and Na2WO4 revisited using neutron powder diffraction

    Directory of Open Access Journals (Sweden)

    A. Dominic Fortes

    2015-06-01

    Full Text Available Time-of-flight neutron powder diffraction data have been collected from Na2MoO4 and Na2WO4 to a resolution of sin (θ/λ = 1.25 Å−1, which is substantially better than the previous analyses using Mo Kα X-rays, providing roughly triple the number of measured reflections with respect to the previous studies [Okada et al. (1974. Acta Cryst. B30, 1872–1873; Bramnik & Ehrenberg (2004. Z. Anorg. Allg. Chem. 630, 1336–1341]. The unit-cell parameters are in excellent agreement with literature data [Swanson et al. (1962. NBS Monograph No. 25, sect. 1, pp. 46–47] and the structural parameters for the molybdate agree very well with those of Bramnik & Ehrenberg (2004. However, the tungstate structure refinement of Okada et al. (1974 stands apart as being conspicuously inaccurate, giving significantly longer W—O distances, 1.819 (8 Å, and shorter Na—O distances, 2.378 (8 Å, than are reported here or in other simple tungstates. As such, this work represents an order-of-magnitude improvement in precision for sodium molybdate and an equally substantial improvement in both accuracy and precision for sodium tungstate. Both compounds adopt the spinel structure type. The Na+ ions have site symmetry .-3m and are in octahedral coordination while the transition metal atoms have site symmetry -43m and are in tetrahedral coordination.

  8. Global Economic Crisis and Career Aspirations among ‘Okada’ Riders in Nigeria: The Influence of Apprenticeship Skills Training

    Directory of Open Access Journals (Sweden)

    Oluranti I. Ogunrinola

    2011-07-01

    Full Text Available In spite of their usefulness as fast movers of passengers and goods in urban traffic congestion, the motor-cycle taxis have been noted for high rate of road traffic crashes inflicting injuries to many and death in some cases. Thus, a number of operators are in the occupation for other purposes rather than making it a lifetime career. This study is therefore aimed at examining such other purposes and future career aspirations of riders. It is also aimed at testing the hypothesis of the probabilistic migration model as propounded by Todaro. The data for the study is from a survey of 777 okada riders in two states of South West Nigeria. Using binary logit regression approach, the determinants of career choice among respondents are examined. The findings of the study shows employment as okada riders are for raising start-up capital in most cases, and that education, current earnings level and apprenticeship skills training among others are statistically significant variables affecting career aspiration among the respondents. Provision of commensurate employment for the educated youths and relaxing capital constraints for those with previous skills training are some of the policy implications of findings.

  9. Influence of fault asymmetric dislocation on the gravity changes

    Directory of Open Access Journals (Sweden)

    Duan Hurong

    2014-08-01

    Full Text Available A fault is a planar fracture or discontinuity in a volume of rock, across which there has been significant displacement along the fractures as a result of earth movement. Large faults within the Earth’s crust result from the action of plate tectonic forces, with the largest forming the boundaries between the plates, energy release associated with rapid movement on active faults is the cause of most earthquakes. The relationship between unevenness dislocation and gravity changes was studied on the theoretical thought of differential fault. Simulated observation values were adopted to deduce the gravity changes with the model of asymmetric fault and the model of Okada, respectively. The characteristic of unevennes fault momentum distribution is from two end points to middle by 0 according to a certain continuous functional increase. However, the fault momentum distribution in the fault length range is a constant when the Okada model is adopted. Numerical simulation experiments for the activities of the strike-slip fault, dip-slip fault and extension fault were carried out, respectively, to find that both the gravity contours and the gravity variation values are consistent when either of the two models is adopted. The apparent difference lies in that the values at the end points are 17. 97% for the strike-slip fault, 25. 58% for the dip-slip fault, and 24. 73% for the extension fault.

  10. RESISTENCIA AL TIZÓN TARDÍO (Phytophthora infestans EN CLONES PROMISORIOS DE PAPA EN COSTA RICA

    Directory of Open Access Journals (Sweden)

    Miguel Barquero

    2005-01-01

    Full Text Available Se determinó la resistencia al tizón tardío presente en 83 genotipos de papa, provenientes de diferentes cruces y fusión de protoplastos de líneas de mejoramiento con las especies silves- tres Solanum bulbocastanum, S. circaeifolium, S. okadae, S. laxissimum, S. berthaultii, S. pinnatisectum y S. commersonii. Los materiales fueron evaluados en el campo, y en el labora- torio se realizó pruebas de foliolos separados, utilizando como inóculo una raza compleja (1- 11 de P. infestans. Los genotipos provenientes de las hibridaciones somáticas o cruces con las especies silvestres S. bulbocastanum, S. circaei-folium y S. okadae fueron los que presentaron los valores más bajos del área bajo la curva de desarrollo de la enfermedad: 60, 80 y 79, res- pectivamente. Las variedades Alpha, Waych'a,Pimpernell y Granola, utilizadas como testigos, presentaron los valores más altos del área bajo la curva 477, 474, 466 y 427, respectivamente.

  11. KCl stimulation increases norepinephrine transporter function in PC12 cells.

    Science.gov (United States)

    Mandela, Prashant; Ordway, Gregory A

    2006-09-01

    The norepinephrine transporter (NET) plays a pivotal role in terminating noradrenergic signaling and conserving norepinephrine (NE) through the process of re-uptake. Recent evidence suggests a close association between NE release and regulation of NET function. The present study evaluated the relationship between release and uptake, and the cellular mechanisms that govern these processes. KCl stimulation of PC12 cells robustly increased [3H]NE uptake via the NET and simultaneously increased [3H]NE release. KCl-stimulated increases in uptake and release were dependent on Ca2+. Treatment of cells with phorbol-12-myristate-13-acetate (PMA) or okadaic acid decreased [3H]NE uptake but did not block KCl-stimulated increases in [3H]NE uptake. In contrast, PMA increased [3H]NE release and augmented KCl-stimulated release, while okadaic acid had no effects on release. Inhibition of Ca2+-activated signaling cascades with KN93 (a Ca2+ calmodulin-dependent kinase inhibitor), or ML7 and ML9 (myosin light chain kinase inhibitors), reduced [3H]NE uptake and blocked KCl-stimulated increases in uptake. In contrast, KN93, ML7 and ML9 had no effect on KCl-stimulated [3H]NE release. KCl-stimulated increases in [3H]NE uptake were independent of transporter trafficking to the plasma membrane. While increases in both NE release and uptake mediated by KCl stimulation require Ca2+, different intracellular mechanisms mediate these two events.

  12. A study of Cs-137 spatial distribution in soil thin sections by digital autoradiography

    Science.gov (United States)

    Korobova, Elena; Dogadkin, Nikolay; Shiryaev, Andrey; Kolotov, Vladimir; Turkov, Victor

    2013-04-01

    Recent studies have proved autoradiography to have high potential in detection of radiation in particles including geological objects [1-3]. We applied digital autoradiography based on usage of image plates to study Cs-137 microdistribution in thin sections of the podzolic sandy soil typical for the Chernobyl remote impact zone 25 years after the accident. The zone is noted for contamination of the so-called condensation type where the contribution of the "hot" fuel particles has been comparatively low. The initial 137Cs contamination level of the study plot approximated 40 Ci/km2. According to the soil core data twenty five years after the accident the main portion of cesium radioisotopes is still concentrated in the 10-20 cm thick surface layer. Thin sections have been prepared from the top 0-10 cm soil layer of the soil profile located on the shoulder of the relatively steep northern slope of the forested hill formed on the Iput river terrace ca 20 km to the east of the town of Novozybkov, Bryansk region. Undisturbed soil sample was impregnated with epoxy resin, then dissected in vertical triplicates and polished to obtain open surface. Autoradiography of the thin sections has clearly shown different patterns of Cs-137 distribution related to its concentration in organic material and on the surface of soil particles. High sensitivity and resolution of the applied technique enables to reveal concentration and dispersion zones on microscale level. Soil micro-morphology has shown to be helpful in deciphering soil components and properties responsible for Cs-137 retention in the soil top layer. References 1. Mihoko Hareyama, Noriyoshi Tsuchiya, Masahiro Takebe and Tadashi Chida. Two-dimensional measurement of natural radioactivity of granitic rocks by photostimulated luminescence technique Geochemical Journal, 2000, 34, 1- 9. 2. Zeissler C. J., R. M. Lindstrom, J. P. McKinley. Radioactive particle analysis by digital autoradiography. Journal of Radioanalytical and

  13. Efficacy of a trunk orthosis with joints providing resistive force on low-back load in elderly persons during static standing

    Directory of Open Access Journals (Sweden)

    Katsuhira J

    2015-09-01

    Full Text Available Junji Katsuhira,1 Ko Matsudaira,2 Tadashi Yasui,3 Shinno Iijima,4 Akihiro Ito4 1Department of Nursing and Rehabilitation Science at Odawara, International University of Health and Welfare, Odawara, Kanagawa, 2Department of Medical Research and Management for Musculoskeletal Pain, 22nd Century Medical and Research Center, The University of Tokyo, Tokyo, 3Kawamura-Gishi Company, Ltd., Daito-shi, Osaka, 4Graduate School of International University of Health and Welfare, Otawara, Tochigi, Japan Purpose: Postural alignment of elderly people becomes poor due to aging, possibly leading to low-back pain and spinal deformity. Although there are several interventions for treating these conditions, no previous study has reported the effectiveness of a spinal orthosis or lumbosacral orthosis (LSO in healthy elderly people without specific spinal deformity. We therefore developed a trunk orthosis to decrease low-back muscle activity while training good postural alignment through resistive force provided by joints with springs (here, called the ORF, which stands for orthosis with joints providing resistive force as a preventive method against abnormal posture and low-back pain in healthy elderly persons. Patients and methods: Fifteen community-dwelling elderly men participated in this study. Participants stood freely for 10 seconds in a laboratory setting under three conditions: without an orthosis, with the ORF, and with an LSO. The Damen corset LSO was selected as it is frequently prescribed for patients with low-back pain. Postural alignment during static standing was recorded using a three-dimensional motion capture system employing infrared cameras. Two force plates were used to record center of pressure. Electromyograms were obtained for bilateral erector spinae (ES, left internal abdominal oblique, and right gluteus medius muscles. Results: Pelvis forward tilt angle tended to increase while wearing the ORF and decrease while wearing the LSO, but these

  14. Occupational safety among dental health-care workers

    Directory of Open Access Journals (Sweden)

    Shigehiro Shimoji

    2010-10-01

    Full Text Available Shigehiro Shimoji1, Kohji Ishihama1,2, Hidefumi Yamada1, Masaki Okayama1, Kouichi Yasuda1,3, Tohru Shibutani3,4, Tadashi Ogasawara2,5, Hiroo Miyazawa2,3, Kiyofumi Furusawa11Department of Oral and Maxillofacial Surgery, Matsumoto Dental University, Shiojiri, Japan; 2Infection Control Team, 3Risk Management Working Team, Matsumoto Dental University Hospital, Shiojiri, Japan; 4Department of Dental Anesthesiology, 5Department of Special Care Dentistry, Matsumoto Dental University, Shiojiri, JapanAbstract: Compared to other health-care workers, dental health-care workers come in close contact with patients and use a variety of sharp and high-speed rotating instruments. It is important to understand the characteristics of the occupational accidents that occur. We reviewed incident reports from April 1, 2005, to March 31, 2010, at Matsumoto Dental University Hospital. In addition, questionnaires dealing with identification of occupational safety issues, especially splash exposures, were conducted for dentists, dental hygienists, and nurses. Thirty-two occupational injuries were reported during the study period, including 23 sharp instrument injuries (71.9%, 6 splash exposures (18.8%, and 3 others. Of the six splash exposures, only two cases involved potential contamination with blood or other potentially infectious patient material. Of the 66 workers who experienced sharps injuries, 20 workers (30.3%, 20/66 reported them to the hospital work safety team. The questionnaire revealed high incident of splash exposures and conjunctiva exposures: 87.9% (51/58 and 60.3% (35/58 in dentists and 88.6% (39/44 and 61.4% (27/44 in dental hygienists. The compliance rate for routine use of protective eyewear was 60.3% (35/58 for dentists and 34.1% (15/44 for hygienists. Of the presented informational items included in the questionnaire, those that strongly persuaded respondents to use protective eyewear were ‘splatters from the patient’s mouth contain blood

  15. Inflammatory cytokines regulate endothelial cell survival and tissue repair functions via NF-κB signaling

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    Kanaji N

    2011-09-01

    Full Text Available Nobuhiro Kanaji1, Tadashi Sato2, Amy Nelson3, Xingqi Wang3, YingJi Li4, Miok Kim5, Masanori Nakanishi6, Hesham Basma3, Joel Michalski3, Maha Farid3, Michael Chandler3, William Pease3, Amol Patil3, Stephen I Rennard3, Xiangde Liu31Division of Hematology, Rheumatology and Respiratory Medicine, Kagawa University, Kagawa, Japan; 2Department of Respiratory Medicine, Juntendo University School of Medicine, Tokyo, Japan; 3Pulmonary and Critical Care Medicine, University of Nebraska Medical Center, Omaha, Nebraska; 4Department of Hygiene and Public Health, Nippon Medical School, Tokyo, Japan; 5Third Department of Internal Medicine, Wakayama Medical University School of Medicine, Wakayama, Japan; 6Department of Internal Medicine, Jeju Medical College, Jeju, Republic of KoreaAbstract: Inflammation contributes to the development of fibrotic and malignant diseases. We assessed the ability of inflammatory cytokines to modulate endothelial cell survival and functions related to tissue repair/remodeling. Treatment with interleukin (IL-1ß or tumor necrosis factor (TNF-α (2 ng/mL led to human pulmonary artery endothelial cells becoming spindle-shaped fibroblast-like cells. However, immunoblot and DNA microarray showed no change in most endothelial and mesenchymal markers. In the presence of IL-1ß or TNF-α, cells were resistant to apoptosis induced by deprivation of serum and growth factor, and were more migratory. In addition, cells treated with IL-1ß or TNF-α contracted collagen gels more robustly. In contrast, transforming growth factor-ß1 did not induce these responses. RNA interference targeting nuclear factor (NF- κB p65 blocked the effects of IL-1ß or TNF-α on cell morphologic change, survival, migration, and collagen gel contraction. These results suggest that endothelial cells may contribute to tissue repair/remodeling via the NF-κB signaling in a milieu of airway inflammation.Keywords: NF-κB, IL-1ß, TNF-α, apoptosis, tissue repair

  16. Travoprost with sofZia® preservative system lowered intraocular pressure of Japanese normal tension glaucoma with minimal side effects

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    Mizoue S

    2014-02-01

    Full Text Available Shiro Mizoue,1 Tadashi Nakano,2 Nobuo Fuse,3 Aiko Iwase,4 Shun Matsumoto,5 Keiji Yoshikawa6 On behalf of the IOP CHANGE Study Group7 1Department of Ophthalmology, Ehime University Graduate School of Medicine, Ehime, Japan; 2Department of Ophthalmology, Jikei University School of Medicine, Tokyo, Japan; 3Department of Integrative Genomics, Tohoku Medical Megabank Organization, Miyagi, Japan; 4Tajimi Iwase Eye Clinic, Gifu, Japan; 5Department of Ophthalmology, Tokyo Teishin Hospital, 6Yoshikawa Eye Clinic, Tokyo, Japan; 7IOP CHecked and Assessed in Normal tension Glaucoma by Exceptional Glaucomatologists Study Group, Japan Background: This study aimed to evaluate the effect of travoprost with sofZia® preservative system for lowering the intraocular pressure (IOP of Japanese normal tension glaucoma (NTG patients. Methods: In this prospective, multicenter, open-label study, Japanese NTG patients with baseline IOPs <20 mmHg were enrolled after three consecutive time measurements taken at screening and baseline visits. Travoprost with sofZia® was instilled once daily. Lowering effect on IOP, conjunctival hyperemia, superficial punctate keratopathy, and adverse events were examined at week 4, 8, and 12 after drug instillation. Results: One-hundred and three of the 107 enrolled patients (baseline IOP =15.2±2.0 mmHg [mean ± standard deviation] completed the study. The mean IOP value as well as percent reduction was significantly reduced at each visit after travoprost with sofZia® initiation (P<0.0001. The conjunctival hyperemia score was 1 or less throughout the study, though it increased significantly over time. No significant change was observed in superficial punctate keratopathy. The cumulative incidence of side effects such as eyelash changes, eyelid pigmentation, and deepening of the upper lid was 47.6%, 27.2%, and 16.5%, respectively. Conclusion: Travoprost preserved with sofZia® effectively lowered the IOP of Japanese NTG patients. It was

  17. An angle encoder for super-high resolution and super-high accuracy using SelfA

    Science.gov (United States)

    Watanabe, Tsukasa; Kon, Masahito; Nabeshima, Nobuo; Taniguchi, Kayoko

    2014-06-01

    Angular measurement technology at high resolution for applications such as in hard disk drive manufacturing machines, precision measurement equipment and aspherical process machines requires a rotary encoder with high accuracy, high resolution and high response speed. However, a rotary encoder has angular deviation factors during operation due to scale error or installation error. It has been assumed to be impossible to achieve accuracy below 0.1″ in angular measurement or control after the installation onto the rotating axis. Self-calibration (Lu and Trumper 2007 CIRP Ann. 56 499; Kim et al 2011 Proc. MacroScale; Probst 2008 Meas. Sci. Technol. 19 015101; Probst et al Meas. Sci. Technol. 9 1059; Tadashi and Makoto 1993 J. Robot. Mechatronics 5 448; Ralf et al 2006 Meas. Sci. Technol. 17 2811) and cross-calibration (Probst et al 1998 Meas. Sci. Technol. 9 1059; Just et al 2009 Precis. Eng. 33 530; Burnashev 2013 Quantum Electron. 43 130) technologies for a rotary encoder have been actively discussed on the basis of the principle of circular closure. This discussion prompted the development of rotary tables which achieve reliable and high accuracy angular verification. We apply these technologies for the development of a rotary encoder not only to meet the requirement of super-high accuracy but also to meet that of super-high resolution. This paper presents the development of an encoder with 221 = 2097 152 resolutions per rotation (360°), that is, corresponding to a 0.62″ signal period, achieved by the combination of a laser rotary encoder supplied by Magnescale Co., Ltd and a self-calibratable encoder (SelfA) supplied by The National Institute of Advanced Industrial Science & Technology (AIST). In addition, this paper introduces the development of a rotary encoder to guarantee ±0.03″ accuracy at any point of the interpolated signal, with respect to the encoder at the minimum resolution of 233, that is, corresponding to a 0.0015″ signal period after

  18. Milnacipran treatment and potential biomarkers in depressed patients following an initial SSRI treatment failure: a prospective, open-label, 24-week study

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    Hashimoto T

    2015-12-01

    Full Text Available Tasuku Hashimoto,1,2 Daiji Sakurai,1 Yasunori Oda,1 Tadashi Hasegawa,3 Nobuhisa Kanahara,4 Tsuyoshi Sasaki,3 Hideki Komatsu,3,5 Junpei Takahashi,1,5 Takahiro Oiwa,6 Yoshimoto Sekine,4,5 Hiroyuki Watanabe,1 Masaomi Iyo1,3 1Department of Psychiatry, Chiba University Graduate School of Medicine, 2Sodegaura Satsukidai Hospital, 3Department of Psychiatry, Chiba University Hospital, 4Division of Medical Treatment and Rehabilitation, Centre for Forensic Mental Health, Chiba University, 5Choshi Kokoro Clinic, 6Mobara Shinkeika Hospital, Chiba, Japan Background: We assessed the effect of switching patients with major depressive disorder to milnacipran following an initial selective serotonin reuptake inhibitor treatment failure, and explored potential biomarkers in their blood.Methods: We conducted a prospective, open-label, 24-week trial. Depression was assessed with the 17-item Hamilton Depression Rating Scale. Patients showing a ≥50% reduction in Hamilton Depression Rating Scale scores from baseline to final visit were considered responders. Regarding adverse effects (AEs, moderate-to-severe AEs were specifically identified as effects that required any medical treatment or that induced treatment withdrawals. We also measured blood levels of various molecules including inflammatory cytokines.Results: Of the 30 participants who enrolled, 17 completed this study. The responder rate was 30% (n=10. Baseline serum levels of interleukin-6 (Z=-2.155; P=0.031 and interleukin-8 (Z=-2.616; P=0.009 were significantly higher when moderate-to-severe AEs were present (n=13 patients with moderate-to-severe AEs. Serum levels of macrophage inflammatory protein-1β showed a significant continuous decrease from the baseline level (Friedman’s test: χ2=23.9, df=4, P<0.001 only in non-responders.Conclusion: These results demonstrate that serum levels of interleukin-6, interleukin-8, and macrophage inflammatory protein-1β as potential blood biomarkers could be utilized

  19. Efficacy and safety of febuxostat in elderly female patients

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    Mizuno T

    2014-09-01

    Full Text Available Tomohiro Mizuno,1,2 Takahiro Hayashi,3 Sayo Hikosaka,1 Yuka Shimabukuro,1 Maho Murase,1 Kazuo Takahashi,2 Hiroki Hayashi,2 Yukio Yuzawa,2 Tadashi Nagamatsu,1 Shigeki Yamada3 1Department of Analytical Pharmacology, Graduate School of Pharmacy, Meijo University, Nagoya, Japan; 2Department of Nephrology, School of Medicine, Fujita Health University, Toyoake, Japan; 3Department of Clinical Pharmacy, School of Medicine, Fujita Health University, Toyoake, Japan Background: Maintenance of low serum urate levels is important for the management of gout. Achieving the recommended serum urate levels of less than 6.0 mg/dL is difficult in elderly (65 years of age or older patients with renal impairment. Xanthine oxidase inhibitors allopurinol and febuxostat are used for this purpose. Although febuxostat had been shown to be efficacious in elderly patients, its safety and efficacy in elderly female patients with hyper­uricemia remain unclear.Objective: The aim of this study was to assess the efficacy and safety of febuxostat in elderly female patients.Methods: We studied a retrospective cohort study. The study included elderly Japanese patients (65 years of age or older who were treated with febuxostat at Fujita Health University Hospital from January 2012 to December 2013. The treatment goal was defined as achievement of serum urate levels of 6.0 mg/dL or lower within 16 weeks; this was the primary endpoint in the present study. Adverse events of febuxostat were defined as more than twofold increases in Common Terminology Criteria for adverse events scores from baseline. Results: We evaluated 82 patients treated with febuxostat during the observation period and classified them into male (n=53 and female (n=29 groups. The mean time to achievement of the treatment goal was significantly shorter in the female group (53 days than in the male group (71 days. There were no significant differences in adverse events between the 2 groups.Conclusion: Our

  20. Tipepidine in children with attention deficit/hyperactivity disorder: a 4-week, open-label, preliminary study

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    Sasaki T

    2014-01-01

    Full Text Available Tsuyoshi Sasaki,1,2 Kenji Hashimoto,3 Masumi Tachibana,1 Tsutomu Kurata,1 Keiko Okawada,1 Maki Ishikawa,1 Hiroshi Kimura,2 Hideki Komatsu,2 Masatomo Ishikawa,2 Tadashi Hasegawa,2 Akihiro Shiina,1 Tasuku Hashimoto,2 Nobuhisa Kanahara,3 Tetsuya Shiraishi,2 Masaomi Iyo1–31Department of Child Psychiatry, Chiba University Hospital, 2Department of Psychiatry, Chiba University Graduate School of Medicine, 3Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, JapanBackground: Tipepidine (3-[di-2-thienylmethylene]-1-methylpiperidine has been used solely as a nonnarcotic antitussive in Japan since 1959. The safety of tipepidine in children and adults has already been established. It is reported that tipepidine inhibits G-protein-coupled inwardly rectifying potassium (GIRK-channel currents. The inhibition of GIRK channels by tipepidine is expected to modulate the level of monoamines in the brain. We put forward the hypothesis that tipepidine can improve attention deficit/hyperactivity disorder (ADHD symptoms by modulating monoaminergic neurotransmission through the inhibition of GIRK channels. The purpose of this open-label trial was to confirm whether treatment with tipepidine can improve symptoms in pediatric patients with ADHD.Subjects and methods: This was a 4-week, open-label, proof-of-efficacy pilot study for pediatric subjects with ADHD. Ten pediatric ADHD subjects (70% male; mean age, 9.9 years; combined [inattentive and hyperactive/impulsive] subtype, n=7; inattentive subtype, n=3; hyperimpulsive subtype, n=0 received tipepidine hibenzate taken orally at 30 mg/day for 4 weeks. All subjects were assessed using the ADHD Rating Scale IV (ADHD-RS, Japanese version, and the Das–Naglieri Cognitive Assessment System (DN-CAS, Japanese version.Results: A comparison of baseline scores and 4-week end-point scores showed that all the ADHD-RS scores (total scores, hyperimpulsive subscores, and inattentive subscores

  1. Antistress effects of Kampo medicine "Yokukansan" via regulation of orexin secretion

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    Katahira H

    2017-03-01

    Full Text Available Haruto Katahira,1 Masataka Sunagawa,1 Daishi Watanabe,1,2 Yasuaki Kanada,1,3 Ayami Katayama,1 Risa Yamauchi,1 Masashi Takashima,4 Shintaro Ishikawa,1 Tadashi Hisamitsu1 1Department of Physiology, 2Department of Neurology, School of Medicine, Showa University, 3Department of Surgery, Showa University Koto Toyosu Hospital, Tokyo, 4Department of Orthopaedic Surgery, Showa University Fujigaoka Hospital, Kanagawa, Japan Objective: Various stressors induce stress responses through the hypothalamic–pituitary–adrenal and the sympathetic–adrenal–medullary axes, which are regulated, in part, by orexin. For example, secretion of orexin in the hypothalamus is increased in rats exposed to the stress of social isolation for 1 week. In this study, the antistress effects of Kampo medicine Yokukansan (YKS via the regulation of orexin secretion were investigated using a rat model.Methods and results: The administration of 300 mg/kg per day of YKS to rats for 1 week significantly decreased the plasma orexin levels compared with non-treated rats, whereas the administration of 1,000 mg/kg of YKS had no effect on orexin levels. Therefore, 300 mg/kg of YKS was an effective dose for controlling orexin secretion. Subsequently, rats were divided into group-housed control (Con, individually housed stress (Stress, and individually housed YKS (300 mg/kg-treated stress (Stress + YKS groups. After 1 week, a resident–intruder aggression test was performed, and the plasma levels of orexin and corticosterone were measured. In the Stress group, aggressive behavior and the levels of corticosterone and orexin significantly increased compared with the Con group; however, these effects were inhibited in the Stress + YKS group. Further, an orexin receptor antagonist (TCS 1102; 10 mg/kg was intraperitoneally administered to rats exposed to isolation stress to determine whether orexin was involved in stress responses. Under these conditions, aggressive behavior and the

  2. Experimental and theoretical studies of the influence of solvent polarity on the spectral properties of two push-pull oxazol-5-(4H)-one compounds.

    Science.gov (United States)

    Jędrzejewska, Beata; Krawczyk, Przemysław; Józefowicz, Marek

    2017-01-15

    Spectral and photophysical properties of two derivatives of the 2-phenyl-1,3-oxazol-5(4H)-ones were studied in 17 solvents of different polarity. These compounds have either push-pull non-centrosymmetric or C3-symmetric structures with electron-withdrawing groups (2-phenyl-oxazolone) introduced onto the triphenylamine. It has been found that their spectral and photophysical properties depend on the structure of the compounds and on the solvent polarity. The non-radiative relaxation process is facilitated by an increase of the solvent polarity. The changes in the electronic absorption and fluorescence maximum positions with solvent polarity were analyzed applying different solvent polarity parameters based on Lippert-Mataga, McRae, Bakhshiev and Kawski theories or ET(N) scale. The long-wavelength absorption band positions exhibit a slight dependence on the solvent, whereas the fluorescence spectra demonstrate substantial positive solvatochromism. It was found that the position of the electronic absorption band depends mainly on the solute polarizability (related to the solvent refraction index function f(n(2))=(n(2)-1)/(2n(2)+1)), whereas the solvent polarity influences the position of the fluorescence band. Quantum chemical calculations of the transition energies and dipole moments at the DFT level have been also performed. The difference between the first excited and ground state dipole moments was found experimentally to be 10.8 D and 13.0 D according to Bakhshiev's model. The experimental values of Δμ were compared to that one obtained from theoretical calculations for various solvents.

  3. 1,6- and 1,7-Regioisomers of Highly Soluble Amino-Substituted Perylene Tetracarboxylic Dianhydrides: Synthesis, Optical and Electrochemical Properties

    Directory of Open Access Journals (Sweden)

    Kew-Yu Chen

    2015-08-01

    Full Text Available 1,6- and 1,7-regioisomers of diamino-substituted perylene tetracarboxylic dianhydrides (PTCDs with different n-alkyl chain lengths (n = 6, 12 or 18 were synthesized and characterized by NMR spectroscopy and high-resolution mass spectrometry. These dyes are highly soluble in most organic solvents and even in nonpolar solvents, such as hexane. To the best of our knowledge, this is the first time the 1,6-diamino-substituted PTCDs (2a–2c have been obtained in pure form. The regioisomers 1a–1c (1,7- and 2a–2c (1,6- exhibit significant differences in their optical characteristics. In addition to the longest wavelength absorption band at around 674 nm, 2a–2c exhibit another shoulder band at ca. 600 nm, and consequently, cover a large part of the visible region relative to those of 1a–1c. Upon excitation, 2a–2c also show larger dipole moment changes than those of 1a–1c; the dipole moments of all compounds have been estimated using Lippert–Mataga equation. Moreover, all the dyes show a unique charge transfer emission in the near-infrared region, of which the peak wavelengths exhibit strong solvatochromism. They all exhibit one irreversible one-electron oxidation and two quasi-reversible one-electron reductions in dichloromethane at modest potentials. Complementary density functional theory calculations performed on these chromophores are reported in order to rationalize their electronic structure and optical properties.

  4. Phenazine containing indeno-furan based colorimetric and “on–off” fluorescent sensor for the detection of Cu{sup 2+} and Pb{sup 2+}

    Energy Technology Data Exchange (ETDEWEB)

    Aggarwal, Komal; Khurana, Jitender M., E-mail: jmkhurana1@yahoo.co.in

    2015-11-15

    A new fluorescent sensor 10a,15a-dihydroxy-10aH-benzo[a]indeno[2′,1′:4,5]furo[2,3-c]phenazin-15 (15aH)-one (1) based on the combination of phenazine and indenofuran moieties was designed and synthesized. Structure of the synthesized sensor has been confirmed by X-ray crystallographic analysis. Absorption and emission spectra of 1 has been studied in solvents of different polarity. The solvent effect on the spectral properties of 1 has been investigated by using the Lippert–Mataga and Reichardt–Dimroth methods. It exhibits high sensitivity and selectivity towards Cu{sup 2+} and Pb{sup 2+} ions over other metal ions by fluorescence quenching. Sensor 1 exhibited a visible color change from light orange to pink, and yellow in the presence of Cu{sup 2+} and Pb{sup 2+}, respectively. The fluorescence of the 1-Cu{sup 2+}/Pb{sup 2+} complexes can be reversibly restored to that of the uncomplexed ligand by using EDTA. Binding stoichiometry and mechanism of Cu{sup 2+} and Pb{sup 2+} ions detection have been investigated. The linear range for the synthesized sensor was found to be 1×10{sup −6}–6.31×10{sup −5} M with detection limit of 1.3×10{sup −6} M. Theoretical calculations were employed to understand the sensing mechanism of the sensors towards Cu{sup 2+}. - Highlights: • A new indeno-furan based “on–off” sensor for detection of Cu{sup 2+} and Pb{sup 2+} has been synthesized. • 1 shows naked-eye visible color changes upon interaction with Cu{sup 2+} and Pb{sup 2+}. • The complex formation of 1 with Cu{sup 2+} and Pb{sup 2+} could be reversed by addition of EDTA.

  5. The spectral properties of (--epigallocatechin 3-O-gallate (EGCG fluorescence in different solvents: dependence on solvent polarity.

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    Vladislav Snitsarev

    Full Text Available (--Epigallocatechin 3-O-gallate (EGCG a molecule found in green tea and known for a plethora of bioactive properties is an inhibitor of heat shock protein 90 (HSP90, a protein of interest as a target for cancer and neuroprotection. Determination of the spectral properties of EGCG fluorescence in environments similar to those of binding sites found in proteins provides an important tool to directly study protein-EGCG interactions. The goal of this study is to examine the spectral properties of EGCG fluorescence in an aqueous buffer (AB at pH=7.0, acetonitrile (AN (a polar aprotic solvent, dimethylsulfoxide (DMSO (a polar aprotic solvent, and ethanol (EtOH (a polar protic solvent. We demonstrate that EGCG is a highly fluorescent molecule when excited at approximately 275 nm with emission maxima between 350 and 400 nm depending on solvent. Another smaller excitation peak was found when EGCG is excited at approximately 235 nm with maximum emission between 340 and 400 nm. We found that the fluorescence intensity (FI of EGCG in AB at pH=7.0 is significantly quenched, and that it is about 85 times higher in an aprotic solvent DMSO. The Stokes shifts of EGCG fluorescence were determined by solvent polarity. In addition, while the emission maxima of EGCG fluorescence in AB, DMSO, and EtOH follow the Lippert-Mataga equation, its fluorescence in AN points to non-specific solvent effects on EGCG fluorescence. We conclude that significant solvent-dependent changes in both fluorescence intensity and fluorescence emission shifts can be effectively used to distinguish EGCG in aqueous solutions from EGCG in environments of different polarity, and, thus, can be used to study specific EGCG binding to protein binding sites where the environment is often different from aqueous in terms of polarity.

  6. Estimation of Ground-State and Singlet Excited-State Dipole Moments of Substituted Schiff Bases Containing Oxazolidin-2-one Moiety through Solvatochromic Methods.

    Science.gov (United States)

    Kumari, Rekha; Varghese, Anitha; George, Louis

    2017-01-01

    Absorption and fluorescence studies on novel Schiff bases (E)-4-(4-(4-nitro benzylideneamino)benzyl)oxazolidin-2-one (NBOA) and (E)-4-(4-(4-chlorobenzylidene amino)benzyl)oxazolidin-2-one (CBOA) were recorded in a series of twelve solvents upon increasing polarity at room temperature. Large Stokes shift indicates bathochromic fluorescence band for both the molecules. The photoluminescence properties of Schiff bases containing electron withdrawing and donating substituents were analyzed. Intramolecular charge transfer behavior can be studied based on the influence of different substituents in Schiff bases. Changes in position and intensity of absorption and fluorescence spectra are responsible for the stabilization of singlet excited-states of Schiff base molecules with different substituents, in polar solvents. This is attributed to the Intramolecular charge transfer (ICT) mechanism. In case of electron donating (-Cl) substituent, ICT contributes largely to positive solvatochromism when compared to electron withdrawing (-NO2) substituent. Ground-state and singlet excited-state dipole moments of NBOA and CBOA were calculated experimentally using solvent polarity function approaches given by Lippert-Mataga, Bakhshiev, Kawskii-Chamma-Viallet and Reichardt. Due to considerable π- electron density redistribution, singlet excited-state dipole moment was found to be greater than ground-state dipole moment. Ground-state dipole moment value which was determined by quantum chemical method was used to estimate excited-state dipole moment using solvatochromic correlations. Kamlet-Abboud-Taft and Catalan multiple linear regression approaches were used to study non-specific solute-solvent interaction and hydrogen bonding interactions in detail. Optimized geometry and HOMO-LUMO energies of NBOA and CBOA have been determined by DFT and TD-DFT/PCM (B3LYP/6-311G (d, p)). Mulliken charges and molecular electrostatic potential have also been evaluated from DFT calculations.

  7. Synthesis, Spectral Characteristics and DFT Studies of the New Dye 2,7-diacetyl-9-((dimethylamino)methylene)-9H-fluorene (DMMF) in Different Solvents.

    Science.gov (United States)

    Asiri, Abdullah M; Ahmed, Saleh A; El-Daly, Samy A; Hussein, Mahmoud A; Al-Soliemy, Amerah M; Osman, Osman I; Shaaban, Mohamed R; Althagafi, Ismail I

    2015-09-01

    The photophysical parameters such as electronic absorption spectra, molar absorptivity(ε), fluorescence spectra and fluorescence quantum yield (φf) of a new dye namely 2,7-diacetyl-9-((dimethylamino)methylene)-9H-fluorene (DMMF) were determined in different solvents. The electronic absorption are less sensitive to medium polarity. A bathochromic shift was observed in emission spectra(ca. 50 nm) upon increase of solvent polarity, which indicates that the singlet excited state (S1) of DMMF is more polar than the singlet ground state (So). Solid crystals of DMMF exhibit intense yellow fluorescence maximum at 550 nm with bandwidth equal 64 nm upon excitation at wavelength 365 nm. The change in dipole moment value (Δμ) was calculated by using the variation of Stokes shift with solvent polarizability (Δf) (Lippert - Mataga plot) and was found to be 7.22 and 5.5 Debye for higher and lower energy of So - S1 (π-π*) H-1 → L and So - S1 (π-π*) H → L, respectively. These results show that, the excited state is more polar than the ground state. The net photochemical quantum yields of photodecomposition of DMMF (φc) were calculated as 7.2 × 10(-5), 1.14 × 10(-4), 1.44 × 10(-4) and 2.11 × 10(-4) in different solvents such as MeOH, CH2Cl2, CHCl3 and CCl4, respectively. DFT/TD-DFT methods were used to study the geometric and electronic structures of DMMF in different solvents. A good agreement was found between the experimental and theoretical results.

  8. Investigation of solvent effect and cyclodextrins on fluorescence properties of ochratoxin A

    Science.gov (United States)

    Hashemi, Javad; Alizadeh, Naader

    2009-07-01

    Fluorescence properties of ochratoxin A (OTA) solutions depend on the pH, solvent polarity and can be influenced by the presence of cyclodextrins (CDs). In this work, the effect of b-cyclodextrin (b-CD) and heptakis-2,6-dimethyl-o-b-cyclodextrin (ome-CD), on fluorescence properties of OTA in aqueous solutions has been investigated by means of steady-state fluorescence at different pHs (range 2-10). Binding constants of OTA/CDs inclusion complexes have been determined by applying by non-linear regression analysis. A 1:1 stoichiometry of OTA/CDs complexes has been observed at all tested pHs. The use of ome-CD generally resulted in the greatest fluorescence intensity. The effects of solvent and pH on the positions of λmax (excitation) and λmax (emission) of OTA was determined. Correlations between the excitation and emission wavelength of OTA (monoanion and dianionic forms) and the solvent parameters were analysed with Lippert-Mataga plots. Results show that the peak position is affected mainly by specific and non-specific types of interactions between the solvent and solute. The fluorescence quenching of OTA by chloroform (aprotic) and water (protic) were studied in methanol as solvent at room temperature. The quenching was found to be appreciable and a non-linear curve with downward curvature was obtained in the Stern-Volmer (SV) plot for the water in the concentration range studied. The quenching efficiency is related to hydrogen bond-donating capacity of the quencher molecule. It was inferred that non-linearity can be attributed to fractional accessibility of fluorophore to quencher. The quenching constant was calculated from the modified SV equation.

  9. Experimental and theoretical studies of the influence of solvent polarity on the spectral properties of two push-pull oxazol-5-(4H)-one compounds

    Science.gov (United States)

    Jędrzejewska, Beata; Krawczyk, Przemysław; Józefowicz, Marek

    2017-01-01

    Spectral and photophysical properties of two derivatives of the 2-phenyl-1,3-oxazol-5(4H)-ones were studied in 17 solvents of different polarity. These compounds have either push-pull non-centrosymmetric or C3-symmetric structures with electron-withdrawing groups (2-phenyl-oxazolone) introduced onto the triphenylamine. It has been found that their spectral and photophysical properties depend on the structure of the compounds and on the solvent polarity. The non-radiative relaxation process is facilitated by an increase of the solvent polarity. The changes in the electronic absorption and fluorescence maximum positions with solvent polarity were analyzed applying different solvent polarity parameters based on Lippert-Mataga, McRae, Bakhshiev and Kawski theories or ETN scale. The long-wavelength absorption band positions exhibit a slight dependence on the solvent, whereas the fluorescence spectra demonstrate substantial positive solvatochromism. It was found that the position of the electronic absorption band depends mainly on the solute polarizability (related to the solvent refraction index function f(n2) = (n2-1) / (2n2 + 1)), whereas the solvent polarity influences the position of the fluorescence band. Quantum chemical calculations of the transition energies and dipole moments at the DFT level have been also performed. The difference between the first excited and ground state dipole moments was found experimentally to be 10.8 D and 13.0 D according to Bakhshiev's model. The experimental values of Δμ were compared to that one obtained from theoretical calculations for various solvents.

  10. Synthesis, characterization and photophysical studies of a novel schiff base bearing 1, 2, 4-Triazole scaffold

    Science.gov (United States)

    Alphonse, Roshmy; Varghese, Anitha; George, Louis

    2016-06-01

    A novel Schiff base derivative containing 1, 2, 4-triazole nucleus (TMPIMP) was synthesized from 4- [1,2,4] triazol-1-ylmethyl-phenylamine and salicylaldehyde in the presence of glacial acetic acid in an ethanolic medium. The synthesized compound was characterized by 1H-NMR, IR and UV spectral analysis. The excitation and emission spectra of triazolyl methyl phenyl imino methyl phenol (abbreviated as TMPIMP) were recorded in various solvents to investigate their solvatochromic behaviour. Dipole moments of the two electronic states of TMPIMP were calculated from solvatochromic spectral shifts. These were correlated with refractive index (η) and dielectric constant (ε) of various solvents. Theoretical calculations were performed to estimate the excited state dipole moment on the basis of different solvent correlation methods, like the Bilot-Kawski, Bakhshiev, Lippert-Mataga, Kawski-Chamma-Viallet and Reichardt methods. The dipole moment in the excited state was found to be higher than that in the ground state due to a substantial redistribution of electron densities and charges. Using a multiple regression analysis, the solvent-solute interactions were determined by means of Kamlet Taft parameters (α, β, π*). Computational studies were performed by Gaussian 09 W software using a time-dependent density functional theory (TD-DFT) in order to calculate the atomic charges and frontier molecular orbital energies in the solvent phase. The calculations indicated that the dipole moment of the molecule in an excited state is much higher than that in a ground state. The chemical stability of TMPIMP was determined by means of chemical hardness (η) using HOMO-LUMO energies. The reactive centers in the molecule were also identified by molecular electrostatic potential (MESP) 3D plots as a result of TD-DFT computational analysis.

  11. Functional study of the effect of phosphatase inhibitors on KCNQ4 channels expressed in Xenopus oocytes

    Institute of Scientific and Technical Information of China (English)

    Tzu-rong SU; Cay-huyen CHEN; Shih-jen HUANG; Chun-yi LEE; Mao-chang SU; Gwan-hong CHEN; Shuan-yow LI; Jiann-jou YANG; Min-jon LIN

    2009-01-01

    Aim: KCNQ4 channels play an important part in adjusting the function of cochlear outer hair cells. The aim of this study was to investigate the effects of ser/thr phosphatase inhibitors on human KCNQ4 channels expressed in Xenopus laevis oocytes. Methods: Synthetic cRNA encoding human KCNQ4 channels was injected into Xenopus oocytes. We used a two-electrode voltage clamp to measure the ion currents in the oocytes. Results: Wild-type KCNQ4 expressed in Xenopus oocytes showed the typical properties of slow activation kinetics and low threshold activation. The outward K~+ current was almost completely blocked by a KCNQ4 blocker, linopirdine (0.25 mmol/L). BIMI (a PKC inhibitor) prevented the effects of PMA (a PKC activator) on the KCNQ4 current, indicating that PKC may be involved in the regulation of KCNQ4 expressed in the Xenopus oocyte system. Treatment with the ser/thr phosphatase inhibitors, cyclosporine (2 μmoVL), calyculin A (2 μmol/L) or okadaic acid (1 μmol/L), caused a significant positive shift in V_(1/2) and a decrease in the conductance of KCNQ4 chan-nels. The V_(1/2) was shifted from-14.6±0.5 to-6.4±0.4 mV by cyclosporine, -18.8±0.5 to-9.2±0.4 mV by calyculin A, and-14.1±0.5 to -0.7±0.6 mV by okadaic acid. Moreover, the effects of these phosphatase inhibitors (okadaic acid or calyculin A) on the induction of a positive shift of V_(1/2) were augmented by further addition of PMA. Conclusion: These results indicate that ser/thr phosphatase inhibitors can induce a shift to more positive potentials of the activation curve of the KCNQ4 current. It is highly likely that the phosphatase functions to balance the phosphorylated state of substrate protein and thus has an important role in the regulation of human KCNQ4 channels expressed in Xenopus oocytes.

  12. Earth and Moon Observations by Thermal Infrared Imager TIR on Hayabusa2 and Applications to Asteroid 162173 Ryugu

    Science.gov (United States)

    Okada, Tatsuaki

    2016-04-01

    The Earth and the Moon were imaged by the thermal infrared imager TIR on Hayabusa2 during the Earth swing-by operation to change the trajectory of the spacecraft with a gravity assist of the Earth's mass. Hayabusa2 is the second sample-return from a near-Earth asteroid organized by Japan Aerospace Exploration Agency, and will visit and explore C-type small asteroid 162173 Ryugu, collect samples from the surface of the asteroid, and return them to the Earth [1-3]. TIR is a thermal infrared imager based on uncooled micro-bolometer array. It covers the temperature range from 150 to 460 K, and resolves the surface by 16° x 12° with 328 x 248 pixels with 0.05° per pixel [4, 5]. After the launch on 3 December 2014, TIR has been proven to work well by function tests, and its operation temperature has been adjusted by using the in-flight deep sky images. On 14 October 2015, TIR has detected the Earth and the Moon simultaneously from the distance of 2 x 107 km, and the alignment of -Z axis between TIR and the spacecraft attitude control system was checked. Afterwards, the Earth-Moon system were imaged many times and we could determine the alignment more precisely. Just after the Earth swing-by, TIR observed the Earth on 4 December 2015 and the Moon on the next day. We compared those thermal images with the calculated temperatures on the Earth and the Moon. It was a good opportunity to check the performance of thermal radiometry of this instrument, because there is no known calibration target before arrival at Ryugu. We found the temperature pattern on the Earth and the Moon are almost equal to the theoretical estimates [6]. The point spread feature shows that a point is imaged as a point, just the same as taken during the pre-flight tests. More detailed results will be presented. References: [1] Tsuda Y. et al. (2013) Acta. Astronautica, 91, 356-362. [2] Tachibana S. et al. (2014) Geochemical Journal, 48, 571-587. [3] Okada T. (2014) Proc. Intl. CJMT-1 workshop on

  13. Spatial Memory Deficit and Tau Hyperphosphorylation Induced by Inhibiting PP2A in Rat Brain

    Institute of Scientific and Technical Information of China (English)

    TIAN Qing; ZHENG Hong-yun; CHEN Juan; LI Hong-lian; GONG Cheng-xin; WANG Jian-zhi

    2005-01-01

    Hyperphosphorylation of Tau in Alzheimer's disease (AD) brain appears to be caused by a down-regulation of protein phosphatase 2A (PP2A). In this study, we selectively inhibited PP2A by injection of okadaic acid (OA) into the Meynert nucleus basalis of rats and found that 0.4 pmol of OA injection induced approximately 60% inhibition of PP2A 24 h after injection, 13% inhibition 48 h after injection and no obvious inhibition 72 h after injection. Hyperphosphorylation of Tau at Ser-198/Ser-199/Ser-202 and Ser-396/Ser-404 and spatial memory deficit of rats were induced 24 h after 0.4 pmol of OA injection. This study suggests that a down-regulation of PP2A may underlie abnormal hyperphosphorylation of cytoskeletal proteins leading to neurofibrillary degeneration in AD.

  14. Relaxation incisions of venomous snake "Japanese mamushi" bites to the hand

    Directory of Open Access Journals (Sweden)

    Sugamata A

    2011-12-01

    Full Text Available Akira Sugamata, Naoki Yoshizawa, Takahiro OkadaDepartment of Plastic and Reconstructive Surgery, Tokyo Medical University Hachioji Medical Center, Tokyo, JapanAbstract: Gloydius blomhoffii, commonly known as Japanese mamushi, is a venomous viper species found widely in Japan. The most frequently bitten regions are the fingers and toes, and severe swelling causes compression of peripheral arteries and/or compartment syndrome of the extremities. We experienced four cases of mamushi bites to the hand, and undertook relaxation incision in the hands of three of these patients. As a result, the patients who underwent relaxation incision did not show any skin necrosis or permanent sensory disturbance in the affected fingers. Relaxation incision can be useful to not only decompress subcutaneous and compartment pressure of the hand, but also to wash out the venom from the bitten region by improving venous and lymphatic drainage.Keywords: mamushi, snakebite, viper, relaxation incision

  15. [Effect of inhibitors serine/threonine protein kinases and protein phosphatases on mitosis progression of synchronized tobacco by-2 cells].

    Science.gov (United States)

    Sheremet, Ia A; Emets, A I; Azmi, A; Vissenberg, K; Verbelen, J-P; Blium, Ia B

    2012-01-01

    In order to investigate the role of various serine/ threonine protein kinases and protein phosphatases in the regulation of mitosis progression in plant cells the influence of cyclin-dependent (olomoucine) and Ca2+ -calmodulin-dependent (W7) protein kinases inhibitors, as well as protein kinase C inhibitors (H7 and staurosporine) and protein phosphatases inhibitor (okadaic acid) on mitosis progression in synchronized tobacco BY-2 cells has been studied. It was found that BY-2 culture treatment with inhibitors of cyclin dependent protein kinases and protein kinase C causes prophase delay, reduces the mitotic index and displaces of mitotic peak as compare with control cells. Inhibition of Ca2+ -calmodulin dependent protein kinases enhances the cell entry into prophase and delays their exit from mitosis. Meanwhile inhibition of serine/threonine protein phosphatases insignificantly enhances of synchronized BY-2 cells entering into all phases of mitosis.

  16. Preparation on a Simple Rat Model of Alzheimer's Disease%拟Alzheimer病简易大鼠模型的制备

    Institute of Scientific and Technical Information of China (English)

    高凤花; 张生林; 张毅; 杨晓娟

    2009-01-01

    目的:制备拟Alzheimer病的简易大鼠模型.方法:大鼠海马CA1区微量注射冈田酸(Okadaic acid OA)隔日1次,共4次,采用Morris水迷宫测试大鼠空间学习记忆能力,免疫组化法观察大鼠海马过度磷酸化tau蛋白的表达,并与正常对照组比较.结果:与对照组比较,模型组大鼠学习记忆能力下降,海马磷酸化tau蛋白表达显著增强.结论:大鼠海马CA1区多次微量注射OA可制备简易拟Alzheimer病大鼠模型.

  17. Postsynaptic Signals Mediating Induction of Long-Term Synaptic Depression in the Entorhinal Cortex

    Directory of Open Access Journals (Sweden)

    Saïd Kourrich

    2008-01-01

    Full Text Available The entorhinal cortex receives a large projection from the piriform cortex, and synaptic plasticity in this pathway may affect olfactory processing. In vitro whole cell recordings have been used here to investigate postsynaptic signalling mechanisms that mediate the induction of long-term synaptic depression (LTD in layer II entorhinal cortex cells. To induce LTD, pairs of pulses, using a 30-millisecond interval, were delivered at 1 Hz for 15 minutes. Induction of LTD was blocked by the NMDA receptor antagonist APV and by the calcium chelator BAPTA, consistent with a requirement for calcium influx via NMDA receptors. Induction of LTD was blocked when the FK506 was included in the intracellular solution to block the phosphatase calcineurin. Okadaic acid, which blocks activation of protein phosphatases 1 and 2a, also prevented LTD. Activation of protein phosphatases following calcium influx therefore contributes to induction of LTD in layer II of the entorhinal cortex.

  18. Use of Biosensors as Alternatives to Current Regulatory Methods for Marine Biotoxins

    Directory of Open Access Journals (Sweden)

    Luis M. Botana

    2009-11-01

    Full Text Available Marine toxins are currently monitored by means of a bioassay that requires the use of many mice, which poses a technical and ethical problem in many countries. With the exception of domoic acid, there is a legal requirement for the presence of other toxins (yessotoxin, saxitoxin and analogs, okadaic acid and analogs, pectenotoxins and azaspiracids in seafood to be controlled by bioassay, but other toxins, such as palytoxin, cyclic imines, ciguatera and tetrodotoxin are potentially present in European food and there are no legal requirements or technical approaches available to identify their presence. The need for alternative methods to the bioassay is clearly important, and biosensors have become in recent years a feasible alternative to animal sacrifice. This review will discuss the advantages and disadvantages of using biosensors as alternatives to animal assays for marine toxins, with particular focus on surface plasmon resonance (SPR technology.

  19. Surveillance guidelines for toxic algal species of Italian sea and lake waters; Indicazioni per il controllo delle specie algali tossiche delle acque marine e lacustri italiane: Studio delle coste e di un lago del Lazio: 1994-1995

    Energy Technology Data Exchange (ETDEWEB)

    Bruno, Milena; Congestri, Roberta; Buzzelli, Elena [Istituot Superiore di Sanita`, Rome (Italy). Lab. di Igiene Ambientale

    1997-09-01

    The health conditions of the coasts of the Rome district and of a large lake in the northern area of the Latium Region were examined to evaluate the toxic algal species, during a 14-month study carried on in cooperation with the Region and the local prevention units of the Region. The study shows the existence of a mesotrophic state in the coastal waters of the lake Bolsena, and a trophic level increased in last years, along the sea coasts of the Rome district. alga populations of genus Dinophysis, harmless to bathing activities, but able to contaminate the edible molluscs with toxins of the okadaic acid group, have been found. The technical occurrences of this study points out the operators`need of a taxonomic atlas, collecting all the toxic algal species known in the Mediterranean basin. This report includes a number of drawings of all the signaled species, each one followed by a fried schedule with the main taxonomic characteristics.

  20. Proteomic profile in Perna viridis after exposed to Prorocentrum lima, a dinoflagellate producing DSP toxins.

    Science.gov (United States)

    Huang, Lu; Zou, Ying; Weng, Hui-wen; Li, Hong-Ye; Liu, Jie-Sheng; Yang, Wei-Dong

    2015-01-01

    In the current study, we compared protein profiles in gills of Perna viridis after exposure to Prorocentrumlima, a dinoflagellate producing DSP toxins, and identified the differential abundances of protein spots using 2D-electrophoresis. After exposure to P. lima, the level of okadaic acid (a main component of DSP toxins) in gills of P. viridis significantly increased at 6 h, but mussels were all apparently healthy without death. Among the 28 identified protein spots by MALDI TOF/TOF-MS, 12 proteins were up-regulated and 16 were down-regulated in the P. lima-exposed mussels. These identified proteins were involved in various biological activities, such as metabolism, cytoskeleton, signal transduction, response to oxidative stress and detoxification. Taken together, our results indicated that the presence of P. lima caused DSP toxins accumulation in mussel gill, and might consequently induce cytoskeletonal disorganization,oxidative stress, a dysfunction in metabolism and ubiquitination/proteasome activity.

  1. [Validation Study for Analytical Method of Diarrhetic Shellfish Poisons in 9 Kinds of Shellfish].

    Science.gov (United States)

    Yamaguchi, Mizuka; Yamaguchi, Takahiro; Kakimoto, Kensaku; Nagayoshi, Haruna; Okihashi, Masahiro; Kajimura, Keiji

    2016-01-01

    A method was developed for the simultaneous determination of okadaic acid, dinophysistoxin-1 and dinophysistoxin-2 in shellfish using ultra performance liquid chromatography with tandem mass spectrometry. Shellfish poisons in spiked samples were extracted with methanol and 90% methanol, and were hydrolyzed with 2.5 mol/L sodium hydroxide solution. Purification was done on an HLB solid-phase extraction column. This method was validated in accordance with the notification of Ministry of Health, Labour and Welfare of Japan. As a result of the validation study in nine kinds of shellfish, the trueness, repeatability and within-laboratory reproducibility were 79-101%, less than 12 and 16%, respectively. The trueness and precision met the target values of notification.

  2. Postsynaptic Signals Mediating Induction of Long-Term Synaptic Depression in the Entorhinal Cortex

    Science.gov (United States)

    Kourrich, Saïd; Glasgow, Stephen D.; Caruana, Douglas A.; Chapman, C. Andrew

    2008-01-01

    The entorhinal cortex receives a large projection from the piriform cortex, and synaptic plasticity in this pathway may affect olfactory processing. In vitro whole cell recordings have been used here to investigate postsynaptic signalling mechanisms that mediate the induction of long-term synaptic depression (LTD) in layer II entorhinal cortex cells. To induce LTD, pairs of pulses, using a 30-millisecond interval, were delivered at 1 Hz for 15 minutes. Induction of LTD was blocked by the NMDA receptor antagonist APV and by the calcium chelator BAPTA, consistent with a requirement for calcium influx via NMDA receptors. Induction of LTD was blocked when the FK506 was included in the intracellular solution to block the phosphatase calcineurin. Okadaic acid, which blocks activation of protein phosphatases 1 and 2a, also prevented LTD. Activation of protein phosphatases following calcium influx therefore contributes to induction of LTD in layer II of the entorhinal cortex. PMID:18670611

  3. Finite element modelling of the 1969 Portuguese tsunami

    Science.gov (United States)

    Guesmia, M.; Heinrich, Ph.; Mariotti, C.

    1996-03-01

    On the 28 th February 1969, the coasts of Portugal, Spain and Morocco were affected by water waves generated by a submarine earthquake (Ms=7.3) with epicenter located off Portugal. The propagation of this tsunami has been simulated by a finite element numerical model solving the Boussinesq equations. These equations have been discretized using the finite element Galerkin method and a Crank-Nicholson scheme in time. The 2-D simulation of the 1969 tsunami is carried out using the hydraulic source calculated from the geophysical model of Okada and seismic parameters of Fukao. The modeled waves are compared with the recorded waves with respect to the travel times, the maximum amplitudes, the periods of the signal. Good agreement is found for most of the studied gauges. The comparison between Boussinesq and shallow-water models shows that the effects of frequency dispersion are minor using Fukao's seismic parameters.

  4. Inversion of SAR data in active volcanic areas by optimization techniques

    Directory of Open Access Journals (Sweden)

    G. Nunnari

    2005-01-01

    Full Text Available The inversion problem concerns the identification of parameters of a volcanic source causing observable changes in ground deformation data recorded in volcanic areas. In particular, this paper deals with the inversion of ground deformation measured by using SAR (Synthetic Aperture Radar interferometry and an inversion approach formulated in terms of an optimization problem is proposed. Based on this inversion scheme, it is shown that the problem of inverting ground deformation data in terms of a single source, of Mogi or Okada type, is numerically well conditioned. In the paper, two case studies of inverting actual SAR data recorded on Mt. Etna during eruptions occurring in 1998 and 2001 are investigated, showing the suitability of the proposed technique.

  5. Short term memory bowing effect is consistent with presentation rate dependent decay.

    Science.gov (United States)

    Tarnow, Eugen

    2010-12-01

    I reanalyze the free recall data of Murdock, J Exp Psychol 64(5):482-488 (1962) and Murdock and Okada, J Verbal Learn and Verbal Behav 86:263-267 (1970) which show the famous bowing effect in which initial and recent items are recalled better than intermediate items (primacy and recency effects). Recent item recall probabilities follow a logarithmic decay with time of recall consistent with the tagging/retagging theory. The slope of the decay increases with increasing presentation rate. The initial items, with an effectively low presentation rate, decay with the slowest logarithmic slope, explaining the primacy effect. The finding that presentation rate limits the duration of short term memory suggests a basis for memory loss in busy adults, for the importance of slow music practice, for long term memory deficiencies for people with attention deficits who may be artificially increasing the presentation rates of their surroundings. A well-defined, quantitative measure of the primacy effect is introduced.

  6. The potential role of natural tumor promoters in marine turtle fibropapillomatosis

    Science.gov (United States)

    Landsberg, J.H.; Balazs, G.H.; Steidinger, K.A.; Baden, D.G.; Work, T.M.; Russel, D.J.

    1999-01-01

    Fibropapillomatosis (FP) in green turtles Chelonia mydas is a debilitating, neoplastic disease that has reached worldwide epizootic levels. The etiology of FP is unknown but has been linked to oncogenic viruses. Toxic benthic dinoflagellates (Prorocentrum spp.) are not typically considered tumorigenic agents, yet they have a worldwide distribution and produce a tumor promoter, okadaic acid (OA). Prorocentrum spp. are epiphytic on macroalgae and seagrasses that are normal components of green turtle diets. Here we show that green turtles in the Hawaiian Islands consume Prorocentrum and that high-risk FP areas are associated with areas where P. lima and P. concavum are both highly prevalent and abundant. The presence of presumptive OA in the tissues of Hawaiian green turtles further suggests exposure and a potential role for this tumor promoter in the etiology of FP.

  7. Trafficking of Na,K-ATPase fused to enhanced green fluorescent protein is mediated by protein kinase A or C

    DEFF Research Database (Denmark)

    Kristensen, B; Birkelund, Svend; Jørgensen, PL

    2003-01-01

    . Responses of similar magnitude were seen after inhibition of protein phosphatase by okadaic acid. Reduction of the amount of Na,K-ATPase in surface plasma membranes through internalization in recycling endosomes may thus in part explain a decrease in Na,K-pump activity following protein kinase activation......Fusion of enhanced green fluorescent protein (EGFP) to the C-terminal of rat Na,K-ATPase a1-subunit is introduced as a novel procedure for visualizing trafficking of Na,K-pumps in living COS-1 renal cells in response to PKA or PKC stimulation. Stable, functional expression of the fluorescent...... along the plasma membrane of COS cells. In unstimulated COS cells, Na,K-EGFP was also present in lysosomes and in vesicles en route from the endoplasmic reticulum to the plasma membrane, but it was almost absent from recycling endosomes labelled with fluorescent transferrin. After activation of protein...

  8. Stemcell Information: SKIP000797 [SKIP Stemcell Database[Archive

    Lifescience Database Archive (English)

    Full Text Available pe II (ACG2) ... 200610 ... Fetus Female ... Yes No ACG II(GM07892)-specific iPS cells 軟骨無発症患者線維芽細胞(GM07892)由来iPS細胞...PS Cell Research and Application, Kyoto University 京都大学iPS細胞研究所 ... Information Only Center for iPS Cell Res...earch and Application,Kyoto University 京都大学iPS細胞研究所 CiRA https://www.cira.kyoto-u.ac.jp/e/index.html ... 251...irected conversion and induced pluripotent stem cells. Okada M, Ikegawa S, Morioka M, Yamashita A, Saito A,

  9. Stemcell Information: SKIP001099 [SKIP Stemcell Database[Archive

    Lifescience Database Archive (English)

    Full Text Available line derived from a neonate.(789013 KURABO)| 新生児皮膚繊維芽細胞(789013 KURABO)由来iPS細胞 human ES-like Res...ication, Kyoto University 京都大学iPS細胞研究所 ... Information Only Center for iPS Cell Research and Application,Kyoto University 京都大学iPS細胞... SKIP001099 ... Normal WT-2-#32 WT-2-#32 ... 0-9 Male ... -- No Nomal human iPS cell... Modeling type II collagenopathy skeletal dysplasia by directed conversion and in...duced pluripotent stem cells. Okada M, Ikegawa S, Morioka M, Yamashita A, Saito A, Sawai H, Murotsuki J, Oha

  10. Stemcell Information: SKIP000801 [SKIP Stemcell Database[Archive

    Lifescience Database Archive (English)

    Full Text Available type II (ACG2) ... 200610 ... 0-9 Male ... Yes No ACG II(S2011-46)-specific iPS cells. Ⅱ型コラーゲン異常症患者線維芽細胞(S2011-46)由来iPS細胞... for iPS Cell Research and Application, Kyoto University 京都大学iPS細胞研究所 ... Information Only Center for iPS Ce...ll Research and Application,Kyoto University 京都大学iPS細胞研究所 CiRA https://www.cira.kyoto-u.ac.jp/e/index.html ... ...a by directed conversion and induced pluripotent stem cells. Okada M, Ikegawa S, Morioka M, Yamashita A, Sai

  11. The Electron/Muon Specific Two Higgs Doublet Model at e+ e- Colliders

    CERN Document Server

    Johansen, Aria R

    2015-01-01

    Recently, Kajiyama, Okada and Yagyu (KOY) proposed an electron/muon specific two Higgs doublet model. In this model, an S3 symmetry suppresses flavor changing neutral currents instead of a Z2 symmetry. In the "Type I" version of the model, the heavy Higgs bosons have a greatly enhanced coupling to electrons and muons. KOY studied the phenomenology of the heavy Higgs bosons at the LHC. In this paper, the phenomenology at electron-positron colliders is studied. For the heavy Higgs mass range between 150 and 210 GeV, bounds from LEP-200 are stronger than those from the LHC. The model allows for the interesting possibility that muon pair production at the ILC can be mediated by s-channel Higgs exchange. This requires an energy scan. The scanning rate and necessary resolution are discussed.

  12. Cell Death Inducing Microbial Protein Phosphatase Inhibitors—Mechanisms of Action

    Directory of Open Access Journals (Sweden)

    Rune Kleppe

    2015-10-01

    Full Text Available Okadaic acid (OA and microcystin (MC as well as several other microbial toxins like nodularin and calyculinA are known as tumor promoters as well as inducers of apoptotic cell death. Their intracellular targets are the major serine/threonine protein phosphatases. This review summarizes mechanisms believed to be responsible for the death induction and tumor promotion with focus on the interdependent production of reactive oxygen species (ROS and activation of Ca2+/calmodulin kinase II (CaM-KII. New data are presented using inhibitors of specific ROS producing enzymes to curb nodularin/MC-induced liver cell (hepatocyte death. They indicate that enzymes of the arachidonic acid pathway, notably phospholipase A2, 5-lipoxygenase, and cyclooxygenases, may be required for nodularin/MC-induced (and presumably OA-induced cell death, suggesting new ways to overcome at least some aspects of OA and MC toxicity.

  13. New series of potent delta-opioid antagonists containing the H-Dmt-Tic-NH-hexyl-NH-R motif.

    Science.gov (United States)

    Li, Tingyou; Shiotani, Kimitaka; Miyazaki, Anna; Fujita, Yoshio; Tsuda, Yuko; Ambo, Akihiro; Sasaki, Yusuke; Jinsmaa, Yunden; Marczak, Ewa; Bryant, Sharon D; Lazarus, Lawrence H; Okada, Yoshio

    2005-12-15

    Heterodimeric compounds H-Dmt-Tic-NH-hexyl-NH-R (R=Dmt, Tic, and Phe) exhibited high affinity to delta- (K(i)delta=0.13-0.89nM) and mu-opioid receptors (K(i)mu=0.38-2.81nM) with extraordinary potent delta antagonism (pA(2)=10.2-10.4). These compounds represent the prototype for a new class of structural homologues lacking mu-opioid receptor-associated agonism (IC(50)=1.6-5.8muM) based on the framework of bis-[H-Dmt-NH]-alkyl (Okada, Y.; Tsuda, Y.; Fujita, Y.; Yokoi, T.; Sasaki, Y.; Ambo, A.; Konishi, R.; Nagata, M.; Salvadori, S.; Jinsmaa, Y.; Bryant, S. D.; Lazarus, L. H. J. Med. Chem.2003, 46, 3201), which exhibited both high mu affinity and bioactivity.

  14. 19th Himalaya-Karakoram-Tibet Workshop

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    The 19th Himalaya-Karakoram-Tibet Workshop (HKT19), as an annual international workshop devoted to presentations of new research findings in the Earth sciences and related disciplines from the Himalaya-Karakoram-Tibet (HKT) region and discussion on the burning issues, was held in Niseko, a famous ski resort in Hokkaido,Japan. The HKT19 Organizing Committee hosted the workshop together with two 21st Century Center of Excellence Programs,namely, COE for the “Neo-Science of Natural History” (Hokkaido University, Project Leader: H. Okada), COE for “Dynamics of the Sun-Earth-Life Interactive System”,(Nagoya University, Project Leader: T.Yasunari), and the Division of Earth and Planetary Sciences, Hokkaido University,

  15. Chemical Diversity, Origin, and Analysis of Phycotoxins

    DEFF Research Database (Denmark)

    Rasmussen, Silas Anselm; Andersen, Aaron John Christian; Andersen, Nikolaj Gedsted;

    2016-01-01

    Microalgae, particularly those from the lineage Dinoflagellata, are very well-known for their ability to produce phycotoxins that may accumulate in the marine food chain and eventually cause poisoning in humans. This includes toxins accumulating in shellfish, such as saxitoxin, okadaic acid......, yessotoxins, azaspiracids, brevetoxins, and pinnatoxins. Other toxins, such as ciguatoxins and maitotoxins, accumulate in fish, where, as is the case for the latter compounds, they can be metabolized to even more toxic metabolites. On the other hand, much less is known about the chemical nature of compounds...... complex natural compounds known to mankind, with chemical structures that show no resemblance to what has been characterized from plants, fungi, or bacteria. In addition, it will summarize algal species known to be related to fish-killing blooms, but from which ichthyotoxins are yet to be characterized....

  16. Demixing and effective volatility of molten alkali carbonate melts in MCFCs

    Energy Technology Data Exchange (ETDEWEB)

    Brenscheidt, T.; Wendt, H. [Institut fuer Chemische Technologie, Darmstadt (Germany)

    1996-12-31

    Since the early investigation of A. Klemm, the demixing of the cations of molten binary salt mixtures with a common anion due to the different mobilities of two different cations had been investigated in numerous experiments and the respective results interpreted in terms of structural features of the melts. 1-1 electrolytes had been preferentially investigated. Okada also reported investigations on lithium carbonate/potassium carbonate mixtures in the temperature range from 980 to 1070 K. From this investigation it is known that the heavier potassium cation is faster than lithium in mixtures which are more concentrated in potassium than x{sub K2CO3} = 0,32 (Chemla effect) whereas below this isotachic concentration lithium is faster. This paper investigates demixing in molten carbonate fuel cells.

  17. Graphene oxide-assisted non-immobilized SELEX of okdaic acid aptamer and the analytical application of aptasensor

    Science.gov (United States)

    Gu, Huajie; Duan, Nuo; Wu, Shijia; Hao, Liling; Xia, Yu; Ma, Xiaoyuan; Wang, Zhouping

    2016-02-01

    Okadaic acid (OA) is a low-molecular-weight marine toxin from shellfish that causes abdominal pain, vomiting and diarrhea, i.e., diarrheic shellfish poisoning. In this study, a ssDNA aptamer that specifically binds to OA with high affinity was obtained via Systematic Evolution of Ligands by Exponential Enrichment (SELEX) assisted by graphene oxide (GO). This aptamer was then applied to fabricate a novel direct competitive enzyme-linked aptamer assay (ELAA). At the optimized conditions, this ELAA method showed a low detection limit (LOD of 0.01 ng/mL), wide linear range (from 0.025 to 10 ng/mL), good recovery rate (92.86-103.34% in OA-spiked clam samples) and repeatability (RSD of 2.28-4.53%). The proposed method can be used to detect OA in seafood products with high sensitivity and can potentially be adapted for the determination of other small molecular analytes.

  18. UV irradiation-induced apoptosis leads to activation of a 36-kDa myelin basic protein kinase in HL-60 cells

    Energy Technology Data Exchange (ETDEWEB)

    Lu, M.L.; Sato, Mitsuhiro; Cao, Boliang; Richie, J.P. [Harvard Medical School, Boston, MA (United States)

    1996-08-20

    UV irradiation induces apoptosis (or programmed cell death) in HL-60 promyelocytic leukemia cells within 3 h. UV-induced apoptosis is accompanied by activation of a 36-kDa myelin basic protein kinase (p36 MBP kinase). This kinase is also activated by okadaic acid and retinoic acid-induced apoptosis. Irrespective of the inducing agent, p36 MBP kinase activation is restricted to the subpopulation of cells actually undergoing apoptosis. Activation of p36 MBP kinase occurs in enucleated cytoplasts, indicating no requirements for a nucleus or fragmented DNA in signaling. We also demonstrate the activation of p36 kinase in tumor necrosis factor-{alpha}-and serum starvation-induced cell death using the human prostatic tumor cell line LNCap and NIH 3T3 fibroblasts, respectively. We postulate that p36 MBP kinase is a common component in diverse signaling pathways leading to apoptosis. 40 refs., 5 figs.

  19. Nodal domains on isospectral quantum graphs: the resolution of isospectrality?

    Energy Technology Data Exchange (ETDEWEB)

    Band, Ram [Department of Physics of Complex Systems, Weizmann Institute of Science, Rehovot 76100 (Israel); Shapira, Talia [Department of Physics of Complex Systems, Weizmann Institute of Science, Rehovot 76100 (Israel); Smilansky, Uzy [Department of Physics of Complex Systems, The Weizmann Institute of Science, Rehovot 76100 (Israel)

    2006-11-10

    We present and discuss isospectral quantum graphs which are not isometric. These graphs are the analogues of the isospectral domains in R{sup 2} which were introduced recently in Gordon et al (1992 Bull. Am. Math. Soc. 27 134-8), Chapman (1995 Am. Math. Mon. 102 124), Buser et al (1994 Int. Math. Res. Not. 9 391-400), Okada and Shudo (2001 J. Phys. A: Math. Gen. 34 5911-22), Jakobson et al (2006 J. Comput. Appl. Math. 194 141-55) and Levitin et al (2006 J. Phys. A: Math. Gen. 39 2073-82)) all based on Sunada's construction of isospectral domains (Sunada T 1985 Ann. Math. 121 196-86). After presenting some of the properties of these graphs, we discuss a few examples which support the conjecture that by counting the nodal domains of the corresponding eigenfunctions one can resolve the isospectral ambiguity.

  20. Is replenishment of the readily releasable pool associated with vesicular movement?

    Science.gov (United States)

    Bui, Loc; Glavinović, Mladen I

    2014-04-01

    At the excitatory synapse of rat hippocampus the short-term synaptic depression observed during long high-frequency stimulation is associated with slower replenishment of the readily-releasable pool. Given that the replenishment rate is also not [Ca(++)]o sensitive this puts into question a widely held notion that the vesicles-constrained by the cytoskeleton and rendered free from such constraints by Ca(++) entry that renders them more mobile-are important in the replenishment of the readily-releasable pool. This raises a question-Is vesicular replenishment of the readily releasable pool associated with significant movement? To answer this question we evaluated how okadaic acid and staurosporine (compounds known to affect vesicular mobility) influence the replenishment rate. We used patterned stimulation on the Schaffer collateral fiber pathway and recorded the excitatory post-synaptic currents (EPSCs) from rat CA1 neurons, in the absence and presence of these drugs. The parameters of a circuit model with two vesicular pools were estimated by minimizing the squared difference between the ESPC amplitudes and simulated model output. [Ca(2+)]o did not influence the progressive decrease of the replenishment rate during long, high frequency stimulation. Okadaic acid did not significantly affect any parameters of the vesicular storage and release system, including the replenishment rate. Staurosporine reduced the replenishment coupling, but not the replenishment rate, and this is owing to the fact that it also reduces the ability of the readily releasable pool to contain quanta. Moreover, these compounds were ineffective in influencing how the replenishment rate decreases during long, high frequency stimulation. In conclusion at the excitatory synapses of rat hippocampus the replenishment of the readily releasable pool does not appear to be associated with a significant vesicular movement, and during long high frequency stimulation [Ca(++)]o does not influence the

  1. Insect peptide CopA3-induced protein degradation of p27Kip1 stimulates proliferation and protects neuronal cells from apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Nam, Seung Taek; Kim, Dae Hong; Lee, Min Bum; Nam, Hyo Jung; Kang, Jin Ku; Park, Mi Jung; Lee, Ik Hwan [Department of Life Science, College of Natural Science, Daejin University, Pocheon, Gyeonggido 487-711 (Korea, Republic of); Seok, Heon [Department of Biomedical Science, Jungwon University, Goesan, Chungcheongbukdo 367-700 (Korea, Republic of); Lee, Dong Gun [School of Life Sciences and Biotechnology, College of Natural Sciences, Kyungpook National University, Daegu 702-701 (Korea, Republic of); Hwang, Jae Sam [Department of Agricultural Biology, National Academy of Agricultural Science, RDA, Suwon 441-707 (Korea, Republic of); Kim, Ho, E-mail: hokim@daejin.ac.kr [Department of Life Science, College of Natural Science, Daejin University, Pocheon, Gyeonggido 487-711 (Korea, Republic of)

    2013-07-19

    Highlights: •CopA3 peptide isolated from the Korean dung beetle has antimicrobial activity. •Our study reported that CopA3 has anticancer and immunosuppressive effects. •We here demonstrated that CopA3 has neurotropic and neuroprotective effects. •CopA3 degrades p27Kip1 protein and this mediates effects of CopA3 on neuronal cells. -- Abstract: We recently demonstrated that the antibacterial peptide, CopA3 (a D-type disulfide dimer peptide, LLCIALRKK), inhibits LPS-induced macrophage activation and also has anticancer activity in leukemia cells. Here, we examined whether CopA3 could affect neuronal cell proliferation. We found that CopA3 time-dependently increased cell proliferation by up to 31 ± 2% in human neuroblastoma SH-SY5Y cells, and up to 29 ± 2% in neural stem cells isolated from neonatal mouse brains. In both cell types, CopA3 also significantly inhibited the apoptosis and viability losses caused by 6-hydroxy dopamine (a Parkinson disease-mimicking agent) and okadaic acid (an Alzheimer’s disease-mimicking agent). Immunoblotting revealed that the p27Kip1 protein (a negative regulator of cell cycle progression) was markedly degraded in CopA3-treated SH-SY5Y cells. Conversely, an adenovirus expressing p27Kip1 significantly inhibited the antiapoptotic effects of CopA3 against 6-hydroxy dopamine- and okadaic acid-induced apoptosis, and decreased the neurotropic effects of CopA3. These results collectively suggest that CopA3-mediated protein degradation of p27Kip1 may be the main mechanism through which CopA3 exerts neuroprotective and neurotropic effects.

  2. A mollusk VDR/PXR/CAR-like (NR1J) nuclear receptor provides insight into ancient detoxification mechanisms

    Energy Technology Data Exchange (ETDEWEB)

    Cruzeiro, Catarina, E-mail: catarinarcruzeiro@hotmail.com [ICBAS - Institute of Biomedical Sciences Abel Salazar, U. Porto - University of Porto (Portugal); CIIMAR/CIMAR - Interdisciplinary Center of Marine and Environmental Research, U. Porto (Portugal); Lopes-Marques, Mónica, E-mail: monicaslm@hotmail.com [ICBAS - Institute of Biomedical Sciences Abel Salazar, U. Porto - University of Porto (Portugal); CIIMAR/CIMAR - Interdisciplinary Center of Marine and Environmental Research, U. Porto (Portugal); Ruivo, Raquel, E-mail: ruivo.raquel@gmail.com [CIIMAR/CIMAR - Interdisciplinary Center of Marine and Environmental Research, U. Porto (Portugal); Rodrigues-Oliveira, Nádia, E-mail: nadia.oliveira@ciimar.up.pt [CIIMAR/CIMAR - Interdisciplinary Center of Marine and Environmental Research, U. Porto (Portugal); Santos, Miguel M., E-mail: santos@ciimar.up.pt [CIIMAR/CIMAR - Interdisciplinary Center of Marine and Environmental Research, U. Porto (Portugal); FCUP - Faculty of Sciences, Department of Biology, U. Porto (Portugal); Rocha, Maria João, E-mail: mjsrocha@netcabo.pt [ICBAS - Institute of Biomedical Sciences Abel Salazar, U. Porto - University of Porto (Portugal); CIIMAR/CIMAR - Interdisciplinary Center of Marine and Environmental Research, U. Porto (Portugal); Rocha, Eduardo, E-mail: erocha@icbas.up.pt [ICBAS - Institute of Biomedical Sciences Abel Salazar, U. Porto - University of Porto (Portugal); CIIMAR/CIMAR - Interdisciplinary Center of Marine and Environmental Research, U. Porto (Portugal); Castro, L. Filipe C., E-mail: filipe.castro@ciimar.up.pt [CIIMAR/CIMAR - Interdisciplinary Center of Marine and Environmental Research, U. Porto (Portugal); FCUP - Faculty of Sciences, Department of Biology, U. Porto (Portugal)

    2016-05-15

    Highlights: • A nuclear receptor orthologue of the NR1J group is isolated from a mollusc. • The molluscan NR1J transactivates gene expression upon exposure to okadaic acid but not a pesticide, esfenvarelate and triclosan. • Lineage specific gene duplications and gene loss have occurred in the NR1J of protostomes with likely impacts on detoxification mechanisms. - Abstract: The origin and diversification of the metazoan endocrine systems represents a fundamental research issue in biology. Nuclear receptors are critical components of these systems. A particular group named VDR/PXR/CAR (NR1I/J) is central in the mediation of detoxification responses. While orthologues have been thoroughly characterized in vertebrates, a sparse representation is currently available for invertebrates. Here, we provide the first isolation and characterization of a lophotrochozoan protostome VDR/PXR/CAR nuclear receptor (NR1J), in the estuarine bivalve the peppery furrow shell (Scrobicularia plana). Using a reporter gene assay, we evaluated the xenobiotic receptor plasticity comparing the human PXR with the S. plana NR1Jβ. Our results show that the molluscan receptor responds to a natural toxin (okadaic acid) in a similar fashion to that reported for other invertebrates. In contrast, the pesticide esfenvalerate displayed a unique response, since it down regulated transactivation at higher concentrations, while for triclosan no response was observed. Additionally, we uncovered lineage specific gene duplications and gene loss in the gene group encoding NRs in protostomes with likely impacts on the complexity of detoxification mechanisms across different phyla. Our findings pave the way for the development of multi-specific sensor tools to screen xenobiotic compounds acting via the NR1I/J group.

  3. Sensitivity of Tsunami Waves and Coastal Inundation/Runup to Seabed Displacement Models: Application to the Cascadia Subduction zone

    Science.gov (United States)

    Jalali Farahani, R.; Fitzenz, D. D.; Nyst, M.

    2015-12-01

    Major components of tsunami hazard modeling include earthquake source characterization, seabed displacement, wave propagation, and coastal inundation/run-up. Accurate modeling of these components is essential to identify the disaster risk exposures effectively, which would be crucial for insurance industry as well as policy makers to have tsunami resistant design of structures and evacuation planning (FEMA, 2008). In this study, the sensitivity and variability of tsunami coastal inundation due to Cascadia megathrust subduction earthquake are studied by considering the different approaches for seabed displacement model. The first approach is the analytical expressions that were proposed by Okada (1985, 1992) for the surface displacements and strains of rectangular sources. The second approach was introduced by Meade (2006) who introduced analytical solutions for calculating displacements, strains, and stresses on triangular sources. In this study, the seabed displacement using triangular representation of geometrically complex fault surfaces is compared with the Okada rectangular representations for the Cascadia subduction zone. In the triangular dislocation algorithm, the displacement is calculated using superposition of two angular dislocations for each of the three triangle legs. The triangular elements could give a better and gap-free representation of the fault surfaces. In addition, the rectangular representation gives large unphysical vertical displacement along the shallow-depth fault edge that generates unrealistic short-wavelength waves. To study the impact of these two different algorithms on the final tsunami inundation, the initial tsunami wave as well as wave propagation and the coastal inundation are simulated. To model the propagation of tsunami waves and coastal inundation, 2D shallow water equations are modeled using the seabed displacement as the initial condition for the numerical model. Tsunami numerical simulation has been performed on high

  4. Cyclic Equibiaxial Tensile Strain Alters Gene Expression of Chondrocytes via Histone Deacetylase 4 Shuttling.

    Directory of Open Access Journals (Sweden)

    Chongwei Chen

    Full Text Available This paper aims to investigate whether equibiaxial tensile strain alters chondrocyte gene expression via controlling subcellular localization of histone deacetylase 4 (HDAC4.Murine chondrocytes transfected with GFP-HDAC4 were subjected to 3 h cyclic equibiaxial tensile strain (CTS, 6% strain at 0.25 Hz by a Flexcell® FX-5000™ Tension System. Fluorescence microscope and western blot were used to observe subcellular location of HDAC4. The gene expression was analyzed by real-time RT-PCR. The concentration of Glycosaminoglycans in culture medium was quantified by bimethylmethylene blue dye; Collagen II protein was evaluated by western blot. Cells phenotype was identified by immunohistochemistry. Cell viability was evaluated by live-dead cell detect kit. Okadaic acid, an inhibitor of HDAC4 nuclear relocation, was used to further validate whether HDAC4 nuclear relocation plays a role in gene expression in response to tension stimulation.87.5% of HDAC4 was located in the cytoplasm in chondrocytes under no loading condition, but it was relocated to the nucleus after CTS. RT-PCR analysis showed that levels of mRNA for aggrecan, collagen II, LK1 and SOX9 were all increased in chondrocytes subjected to CTS as compared to no loading control chondrocytes; in contrast, the levels of type X collagen, MMP-13, IHH and Runx2 gene expression were decreased in the chondrocytes subjected to CTS as compared to control chondrocytes. Meanwhile, CTS contributed to elevation of glycosaminoglycans and collagen II protein, but did not change collagen I production. When Okadaic acid blocked HDAC4 relocation from the cytoplasm to nucleus, the changes of the chondrocytes induced by CTS were abrogated. There was no chondrocyte dead detected in this study in response to CTS.CTS is able to induce HDAC4 relocation from cytoplasm to nucleus. Thus, CTS alters chondrocytes gene expression in association with the relocation of HDAC4 induced by CTS.

  5. Malaria and Anemia among Children in a Low Resource Setting In Nigeria

    Directory of Open Access Journals (Sweden)

    AA Onifade

    2012-09-01

    Full Text Available Background: This study aimed at determining the prevalence of malaria and anemia among child­ren in rural community of Okada, Edo State Nigeria, as well as to assess the level of use of Insecti­cide treated bed nets and its impact on prevalence of malaria and anemia among study population. Methods: Thick blood films from 226 children with signs and symptoms of malaria in Okada commu­nity were stained and examined for presence of malaria parasites. Hemoglobin concentra­tion of all children was also determined using standard method. Result: A total of 185 (81.9% children were infected with malaria parasite. Malaria parasitaemia was significantly affected by age (P =0.003. A significantly higher number of positive cases of malaria and anemia was observed in rainy season as compared to dry season (P<0.05. The prevalence of anemia in children was 47.3%. Malaria was a risk factor for development of anemia in children (OR=2.551; 95% CI=1.227, 5.305; P=0.015. Use of insecticide treated bed nets was recorded in 11(4.9% of children studied, and did not significantly reduce the prevalence of malaria and anemia. However among malaria parasite infected children, its use significantly reduced the prevalence of anemia (OR=0.126; 95%CI = 0.015, 1.047; P= 0.031. Conclusion: Malaria and anemia among children was high malaria intervention progammes by rele­vant agencies is strongly advocated.

  6. Risk associated with toxic blooms of marine phytoplankton functional groups on Artemia franciscana

    Institute of Scientific and Technical Information of China (English)

    Ana Dors; Mara Carmen Bartolom; Sebastin Snchez-Fortn

    2014-01-01

    Objective:To study mortality of copepod Artemia franciscana against the occurrence of harmful marine algae and possible toxicological changes exhibited by binary and tertiary combinations of these harmful algae toxins. Methods:Tweenty four hours acute toxicity assays were performed with selected concentrations of Alexandrium minutum, Prorocentrum lima and Nitzschia N1c1 living cells. Additionally, the results were analyzed using the median-effect/combination index (CI)-isobologram equation to assess possible changes in the toxic effect induced by phytoplankton functional groups. Results:Biotoxin equivalent values obtained by immunodetection were (2.12±0.10), (8.60±1.30) and (4.32±1.67) pg/cell for saxitoxin, okadaic acid and domoic acid, respectively. The 24-h LC50 values estimated to saxitoxin and okadaic acid equivalents were 4.06 and 6.27 µg/L, significantly below the value obtained for Nitzschia N1c1, which was established at 467.33 µg/L. CI analysis applied on phytoplankton assemblages showed that both ternary mixture as the binary combinations exhibited antagonic action on toxic effects in Artemia nauplii, which were significantly lower than the toxic effect exhibited by each species studied. Conclusions:These results show that, although these harmful algae represent a serious risk to estuarine zooplankton community, the presence of phytoplankton functional groups within the same bloom can reduce the potential risk compared to the expected risk when each of the phytoplankton groups are evaluated individually.

  7. Modeling tsunamis from earthquake sources near Gorringe Bank southwest of Portugal

    Science.gov (United States)

    Gjevik, B.; Pedersen, G.; Dybesland, E.; Harbitz, C. B.; Miranda, P. M. A.; Baptista, M. A.; Mendes-Victor, L.; Heinrich, P.; Roche, R.; Guesmia, M.

    1997-12-01

    The Azores-Gibraltar fracture zone with the huge bathymetric reliefs in the area southwest of Portugal is believed to have been the source of large historic tsunami events. This report describes simulations of tsunami generation and propagation from sources near the Gorringe Bank. The well-documented 1969 tsunami event is examined both with a ray-tracing technique and with finite difference models based on various shallow water equations. Both methods show that the most likely source location is southeast of the Gorringe Bank near the epicenter location determined from seismic data. The tsunami source is calculated by formulas given by Okada [1985] for surface deformation of an elastic half-space caused by faulting. Observed wave amplitude and travel time and values computed from an initial wave field according to Okada [1985] formulas show acceptable agreement for most stations along the coast of Portugal and Spain. However, in order to explain a large primary wave with downward displacement observed on the coast of Morocco, an alternative source model with a larger area of downward displacement has been introduced. This also leads to a better overall fit with observed travel time. Implications for disastrous events, as the one in 1755, are also discussed. Linear hydrostatic shallow water models are used for most of the simulations, but the importance of nonlinearity and dispersion is examined with the Boussinesq equations. The sensitivity of the solution to changes in the location and the strength of the source is discussed, and a series of grid refinement studies are performed in order to assess the accuracy of the simulations.

  8. Role of VASP phosphorylation for the regulation of microglia chemotaxis via the regulation of focal adhesion formation/maturation.

    Science.gov (United States)

    Lee, S; Chung, C Y

    2009-12-01

    Microglia activation and migration are known to play crucial roles for the response to brain injuries. Extracellular ADP was reported to induce microglia chemotaxis and membrane ruffles through P2Y12 receptor. In this study, we examined the role of VASP phosphorylation in ADP-induced microglia chemotaxis and membrane ruffle formation. ADP stimulation transiently increased intracellular cAMP level, VASP phosphorylation at Ser153, membrane ruffle formation, and chemotaxis. PKA inhibitor effectively inhibited VASP phosphorylation and chemotaxis, indicating that P2Y12-mediated activation of PKA and subsequent VASP phosphorylation are involved in the regulation of microglia chemotaxis. Forskolin and okadaic acid induced sustained VASP phosphorylation at a high level, causing a significant reduction of the retraction of membrane ruffles and chemotaxis. In forskolin- or okadaic acid-treated cells, phosphorylated VASP remained at the membrane cortex, and size and number of mature focal adhesions were not increased, indicating that prolonged phosphorylation of VASP could inhibit transformation of focal complexes into focal adhesions. VASP knockdown cells showed markedly reduced frequency and distance of membrane ruffling upon ADP stimulation, reinforcing the idea that VASP is required for the ruffle formation. Cells expressing GFP-VASP(S153A) also showed a significant reduction of protrusion distance during ruffle formation, but the frequency and the distance of retraction were not affected by FSK at all. This result suggests that dephosphorylation of VASP might be required for the growth of adhesion strength during membrane retraction. Our results suggest that VASP phosphorylation by PKA plays an important role in membrane ruffle formation and chemotaxis via the regulation of focal adhesion formation/maturation.

  9. Study on Alzheimer's disease model

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    It is well known that the main brain lesion in Alzheimer's disease (AD) brain is neurofibrillary tangles (NFT) and senile plaques (SP). The amount of NFT is positively correlated with clinical degree of dementia in AD. It is also well studied that the major component of NFT is abnormally hyperphosphorylated microtubule associated protein tau that is caused by an imbalance of protein kinase and protein phosphatase (PP). To reconstitute a specific AD model based on the above hypothesis, we have injected separately calcium calmodulin dependent protein kinase (CaMKKII) activator, bradykinin and PP-2B inhibitor, cyclosporin A into rat hippocampus in the present study. The results showed that the injection of bradykinin caused learning and memory deficient in rats as well as Alzheimer-like tau phosphorylation, including Ser-262/356, Thr-231/235 and Ser-396/404. On the other hand, the injection of cyclosporin A induced the same phosphorylation sites as above except Ser-262/356, however, it did not mimic rat behavior abnormality as bradykinin injection did. The data suggested that activating of CaMKII and the phosphorylation of Ser-262/356 at tau might responsible for the lesion of learning and memory in our model rats. We also incubated PP-2A and PP-1 inhibitor, okadaic acid with human neuroblastoma cell line (SH-SY5Y), and found that (1) inhibition of above PPs induced Alzheimer-like phosphorylation and accumulation of neurofilaments, and Alzheimer-like microtubule disruption, (2) melatonin showed certain protection of the cell from okadaic acid toxicity. The data obtained from this study is significant in AD specific model study.

  10. Diarrhetic Shellfish Toxins and Other Lipophilic Toxins of Human Health Concern in Washington State

    Directory of Open Access Journals (Sweden)

    Bich-Thuy L. Eberhart

    2013-05-01

    Full Text Available The illness of three people in 2011 after their ingestion of mussels collected from Sequim Bay State Park, Washington State, USA, demonstrated the need to monitor diarrhetic shellfish toxins (DSTs in Washington State for the protection of human health. Following these cases of diarrhetic shellfish poisoning, monitoring for DSTs in Washington State became formalized in 2012, guided by routine monitoring of Dinophysis species by the SoundToxins program in Puget Sound and the Olympic Region Harmful Algal Bloom (ORHAB partnership on the outer Washington State coast. Here we show that the DSTs at concentrations above the guidance level of 16 μg okadaic acid (OA + dinophysistoxins (DTXs/100 g shellfish tissue were widespread in sentinel mussels throughout Puget Sound in summer 2012 and included harvest closures of California mussel, varnish clam, manila clam and Pacific oyster. Concentrations of toxins in Pacific oyster and manila clam were often at least half those measured in blue mussels at the same site. The primary toxin isomer in shellfish and plankton samples was dinophysistoxin-1 (DTX-1 with D. acuminata as the primary Dinophysis species. Other lipophilic toxins in shellfish were pectenotoxin-2 (PTX-2 and yessotoxin (YTX with azaspiracid-2 (AZA-2 also measured in phytoplankton samples. Okadaic acid, azaspiracid-1 (AZA-1 and azaspiracid-3 (AZA-3 were all below the levels of detection by liquid chromatography tandem mass spectrometry (LC-MS/MS. A shellfish closure at Ruby Beach, Washington, was the first ever noted on the Washington State Pacific coast due to DSTs. The greater than average Fraser River flow during the summers of 2011 and 2012 may have provided an environment conducive to dinoflagellates and played a role in the prevalence of toxigenic Dinophysis in Puget Sound.

  11. Geodetic imaging of thermal deformation in geothermal reservoirs - production, depletion and fault reactivation

    Science.gov (United States)

    Im, Kyungjae; Elsworth, Derek; Guglielmi, Yves; Mattioli, Glen S.

    2017-05-01

    We investigate thermally induced surface deformation in geothermal systems. To define source mechanisms at depth, we assess the mechanical process of subsurface deformation by assuming a spherically cooled fractured reservoir in an infinite medium and derive relations that define magnitudes of thermal contraction, stress change and permeability evolution. The magnitude of thermal deformation in typical geothermal system is larger than anticipated and suggests two different modalities of surface subsidence - thermal contraction and fault reactivation. Here, surface deformation (vertical displacement, surface tilt and horizontal strain) induced by the two different modalities are assessed with Mogi (contraction) and Okada (slip) models and compared with instrumental sensitivity of high precision surface geodetic tools. We show that 1 year of geothermal operation at 10 MW with a power plant conversion efficiency of 12% can yield 3.0 × 104 m3 of subsurface volume change. For a reservoir at 2000 m depth, this induces 1.7 mm of vertical surface displacement, 800 nano-radians of surface tilt and 900 nano-strains of surface strain. This result implies that typically observed magnitudes of surface subsidence (order of cm/year) are naturally expected in massive (100 MW scale) geothermal operations and observed surface subsidence may largely be the result of thermal contraction. Conversely, thermal unloading can trigger fault reactivation. Analysis with an Okada slip model shows these shear offsets on pre-existing faults can also result in surface deformations of considerable magnitude. Our analysis of field operational data from various geothermal projects suggests that both thermal contraction and slow fault reactivation may contribute to the observed large surface deformation. Comparison of predicted deformation with instrumental sensitivity of high precision surface tools confirms that geodetic signals, especially tilt and strain, are indeed sufficiently large to

  12. Solvatochromism and linear solvation energy relationship of the kinase inhibitor SKF86002

    Science.gov (United States)

    Khattab, Muhammad; Van Dongen, Madeline; Wang, Feng; Clayton, Andrew H. A.

    2017-01-01

    We studied the spectroscopic characteristics of SKF86002, an anti-inflammatory and tyrosine kinase inhibitor drug candidate. Two conformers SKF86002A and SKF86002B are separated by energy barriers of 19.68 kJ·mol- 1 and 6.65 kJ·mol- 1 due to H-bonds, and produce the three major UV-Vis absorption bands at 325 nm, 260 nm and 210 nm in cyclohexane solutions. This environment-sensitive fluorophore exhibited emission in the 400-500 nm range with a marked response to changes in environment polarity. By using twenty-two solvents for the solvatochromism study, it was noticed that solvent polarity, represented by dielectric constant, was well correlated with the emission wavelength maxima of SKF86002. Thus, the SKF86002 fluorescence peak red shifted in aprotic solvents from 397.5 nm in cyclohexane to 436 nm in DMSO. While the emission maximum in hydrogen donating solvents ranged from 420 nm in t-butanol to 446 nm in N-methylformamide. Employing Lippert-Mataga, Bakhshiev and Kawski models, we found that one linear correlation provided a satisfactory description of polarity effect of 18 solvents on the spectral changes of SKF86002 with R2 values 0.78, 0.80 and 0.80, respectively. Additionally, the multicomponent linear regression analysis of Kamlet-Taft (R2 = 0.94) revealed that solvent acidity, basicity and polarity accounted for 31%, 24% and 45% of solvent effects on SKF86002 emission, respectively. While Catalán correlation (R2 = 0.92) revealed that solvatochromic change of SKF86002 emission was attributed to changes in solvent dipolarity (71%), solvent polarity (12%), solvent acidity (11%) and solvent basicity (6%). Plot of Reichardt transition energies and emission energies of SKF86002 in 18 solvents showed also a linear correlation with R2 = 0.90. The dipole moment difference between excited and ground state was calculated to be 3.4-3.5 debye.

  13. Photophysical properties of oligophenylene ethynylenes modified by donor and/or acceptor groups.

    Science.gov (United States)

    Yamaguchi, Yoshihiro; Shimoi, Yukihiro; Ochi, Takanori; Wakamiya, Tateaki; Matsubara, Yoshio; Yoshida, Zen-ichi

    2008-06-12

    To create highly fluorescent organic compounds in longer wavelength regions, and to gain physical chemistry insight into the photophysical characteristics, we investigated photophysical properties (Phi(f), lambda(em), tau, lambda(abs), epsilon, k(r), and k(d)) and their controlling factor dependence of the following pi-conjugated molecular rods consisting of p-phenyleneethynylene units modified by donor (OMe) and/or acceptor (CN): (1) side-donor modification systems (SD systems), (2) side-acceptor modification systems (SA systems), and (3) systems consisting of donor block and acceptor block (BL systems). As a result, very high Phi(f) values (>0.95) were obtained for BL systems. Bathochromic shifts of lambd(em) in the same pi conjugation length were largest for BL systems. Thus we succeeded in the creation of highly efficient light emitters in the longer wavelength region by block modification (e.g., Phi(f) = 0.97, lambda(em) = 464 nm for BL-9), contrary to expectation from energy gap law. Considerably intense solid emission (Phi(f) approximately 0.5) in the longer wavelength region (500-560 nm) was also found for BL systems, presumably because of molecular orientation that hinders the self-quenching of fluorescence in solids. From (1) a Lippert-Mataga plot, (2) density functional theory (DFT) and time-dependent DFT (TD-DFT) calculations, and (3) the positive linear relationship between the optical transition energy (nu(em)) and the difference between the highest occupied molecular orbital of the donor and the lowest unoccupied molecular orbital of the acceptor (HOMO(D)-LUMO(A) difference), it is elucidated that the excited singlet (S1) state of BL systems has a high charge transfer nature. The number (n) of energetically equivalent dipolar structure (EEDS) units in the oligoarylene ethynylenes is shown to be a measure of the effective pi conjugation length in the S1 state. The S1 state planarity increases with n values of EEDS units and by the introduction of

  14. Anti-inflammatory effects of budesonide in human lung fibroblasts are independent of histone deacetylase 2

    Directory of Open Access Journals (Sweden)

    Wang X

    2013-08-01

    Full Text Available Xingqi Wang,1 Amy Nelson,1 Zachary M Weiler,1 Amol Patil,1 Tadashi Sato,1 Nobuhiro Kanaji,1 Masanori Nakanishi,1 Joel Michalski,1 Maha Farid,1 Hesham Basma,1 Tricia D LeVan,1 Anna Miller-Larsson,2 Elisabet Wieslander,2 Kai-Christian Muller,3 Olaf Holz,3 Helgo Magnussen,3 Klaus F Rabe,3 Xiangde Liu,1 Stephen I Rennard1 1Pulmonary, Critical Care, Sleep and Allergy Division, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, USA; 2AstraZeneca R&D Molndal, Molndal, Sweden; 3Hospital Grosshansdorf, Center for Pneumology and Thoracic Surgery, Grosshansdorf, Germany Objective and design: Reduced expression of histone deacetylase 2 (HDAC2 in alveolar macrophages and epithelial cells may account for reduced response of chronic obstructive pulmonary disease (COPD patients to glucocorticoids. HDAC2 expression and its role in mediating glucocorticoid effects on fibroblast functions, however, has not been fully studied. This study was designed to investigate whether HDAC2 mediates glucocorticoid effects on release of inflammatory cytokines and matrix metalloproteinases (MMPs from human lung fibroblasts. Methods: Human lung fibroblasts (HFL-1 cells were stimulated with interleukin (IL-1β plus tumor necrosis factor (TNF-α in the presence or absence of the glucocorticoid budesonide. Cytokines (IL-6 and IL-8 were quantified by enzyme linked immunosorbent assay (ELISA and MMPs (MMP-1 and MMP-3 by immunoblotting in culture medium. The role of HDAC2 was investigated using a pharmacologic inhibitor as well as a small interfering ribonucleic acid (siRNA targeting HDAC2. Results: We have demonstrated that budesonide concentration-dependently (10-10–10-7 M inhibited IL-6, IL-8, MMP-1, and MMP-3 release by HFL-1 cells in response to IL-1β plus TNF-a. While an HDAC inhibitor significantly blocked the inhibitory effect of budesonide on human bronchial epithelial cells (HBECs and monocytes (THP-1 cells, it did not block the inhibitory

  15. Efficacy and safety of febuxostat in the treatment of hyperuricemia in stable kidney transplant recipients

    Directory of Open Access Journals (Sweden)

    Sofue T

    2014-02-01

    Full Text Available Tadashi Sofue,1 Masashi Inui,2 Taiga Hara,1 Yoko Nishijima,1 Kumiko Moriwaki,1 Yushi Hayashida,3 Nobufumi Ueda,3 Akira Nishiyama,4 Yoshiyuki Kakehi,3 Masakazu Kohno1 1Division of Nephrology and Dialysis, Department of Cardiorenal and Cerebrovascular Medicine, Kagawa University, Kagawa, 2Department of Urology, Tokyo Women's Medical University, Tokyo, 3Department of Urology, 4Department of Pharmacology, Kagawa University, Kagawa, Japan Background: Post-transplant hyperuricemia (PTHU, defined as serum uric acid concentration ≥7.0 mg/dL or need for treatment with allopurinol or benzbromarone, reduces long-term allograft survival in kidney transplant recipients. Febuxostat, a new nonpurine selective xanthine oxidase inhibitor, is well tolerated in patients with moderate renal impairment. However, its efficacy and safety in kidney recipients with PTHU is unclear. We therefore assessed the efficacy and safety of febuxostat in stable kidney transplant recipients with PTHU. Methods: Of 93 stable adult kidney transplant recipients, 51 were diagnosed with PTHU (PTHU group and 42 were not (NPTHU group. Of the 51 patients with PTHU, 26 were treated with febuxostat (FX group and 25 were not (NFX group, at the discretion of each attending physician. One-year changes in serum uric acid concentrations, rates of achievement of target uric acid (<6.0 mg/dL, estimated glomerular filtration rates in allografts, and adverse events were retrospectively analyzed in the FX, NFX, and NPTHU groups. Results: The FX group showed significantly greater decreases in serum uric acid (-2.0±1.1 mg/dL versus 0.0±0.8 mg/dL per year, P<0.01 and tended to show a higher rate of achieving target uric acid levels (50% versus 24%; odds ratio 3.17 [95% confidence interval 0.96–10.5], P=0.08 than the NFX group. Although baseline allograft estimated glomerular filtration rates tended to be lower in the FX group than in the NFX group (40±14 mL/min/1.73 m2 versus 47±19 mL/min/1.73 m2

  16. Modulation of neurite branching by protein phosphorylation in cultured rat hippocampal neurons.

    Science.gov (United States)

    Audesirk, G; Cabell, L; Kern, M

    1997-09-20

    phosphatases (okadaic acid, cyclosporin A and FK506) and stimulators of PKA (SP-cAMPS) or PKC (phorbol 12-myristate 13-acetate), increased dendrite branching. Only FK506 and phorbol 12-myristate 13-acetate stimulated axon branching. A subset of these agents was tested to confirm their effects on protein phosphorylation in this preparation. Okadaic acid, FK506 and SP-cAMPS all increased protein phosphorylation; KT5720 and KN62 decreased protein phosphorylation. On Western blots, the position of MAP2c extracted from cultures exposed to okadaic acid was slightly shifted toward higher molecular weight, suggesting greater phosphorylation, while the position of MAP2c from cultures exposed to KT5720 and KN62 was slightly shifted toward lower molecular weight, suggesting less phosphorylation. We conclude that protein phosphorylation modulates both dendrite branching and axon branching, but with differences in sensitivity to phosphorylation and/or dephosphorylation by specific kinases and phosphatases.

  17. Determination of the variability of both hydrophilic and lipophilic toxins in endemic wild bivalves and carnivorous gastropods from the southern part of Chile.

    Science.gov (United States)

    Zamorano, Ruben; Marín, Michelle; Cabrera, Fabiola; Figueroa, Diego; Contreras, Cristóbal; Barriga, Andrés; Lagos, Néstor; García, Carlos

    2013-01-01

    The aim of this study was to analyse and determine the composition of paralytic shellfish poisoning (PSP) toxins and lipophilic toxins in the Region of Aysén, Chile, in wild endemic mussels (Mytilus chilensis, Venus antiqua, Aulacomya ater, Choromytilus chorus, Tagelus dombeii and Gari solida) and in two endemic carnivorous molluscs species (Concholepas concholepas and Argobuccinum ranelliforme). PSP-toxin contents were determined by using HPLC with fluorescence detection, while lipophilic toxins were determined by using LC-MS/MS. Mean concentrations for the total of PSP toxins were in the range 55-2505 μg saxitoxin-equivalent/100 g. The two most contaminated samples for PSP toxicity were bivalve Gari solida and carnivorous Argobuccinum ranelliforme with 2505 ± 101 and 1850 ± 137 μg saxitoxin-equivalent/100 g, respectively (p < 0.05). The lipophilic toxins identified were okadaic acid, dinophysistoxin-1 (DTX-1), azaspiracid-1 (AZA-1), pectenotoxin-2 (PTX-2) and yessotoxins (YTX). All analysed molluscs contained lipophilic toxins at levels ranging from 56 ± 4.8 to 156.1 ± 8.2 μg of okadaic acid-equivalent/kg shellfish together with YTX at levels ranging from 1.0 ± 0.1 to 18 ± 0.9 μg of YTX-equivalent/kg shellfish and AZA at levels ranging from 3.6 ± 0.2 to 31 ± 2.1 μg of AZA-equivalent/kg shellfish. Furthermore, different bivalves and gastropods differ in their capacity of retention of lipophilic toxins, as shown by the determination of their respective lipophilic toxins levels. In all the evaluated species, the presence of lipophilic toxins associated with biotransformation in molluscs and carnivorous gastropods was not identified, in contrast to the identification of PSP toxins, where the profiles identified in the different species are directly related to biotransformation processes. Thus, this study provides evidence that the concentration of toxins in the food intake of the evaluated species (Bivalvia and Gastropoda class) determines the degree of

  18. Dark matter relic density in Gauss-Bonnet braneworld cosmology

    Energy Technology Data Exchange (ETDEWEB)

    Meehan, Michael T.; Whittingham, Ian B., E-mail: Michael.Meehan@my.jcu.edu.au, E-mail: Ian.Whittingham@jcu.edu.au [College of Science, Technology and Engineering, James Cook University, 1 James Cook Dr., Townsville 4811 (Australia)

    2014-12-01

    The relic density of symmetric and asymmetric dark matter in a Gauss-Bonnet (GB) modified Randall-Sundrum (RS) type II braneworld cosmology is investigated. The existing study of symmetric dark matter in a GB braneworld (Okada and Okada, 2009) found that the expansion rate was reduced compared to that in standard General Relativity (GR), thereby delaying particle freeze-out and resulting in relic abundances which are suppressed by up to O(10{sup −2}). This is in direct contrast to the behaviour observed in RS braneworlds where the expansion rate is enhanced and the final relic abundance boosted. However, this finding that relic abundances are suppressed in a GB braneworld is based upon a highly contrived situation in which the GB era evolves directly into a standard GR era, rather than passing through a RS era as is the general situation. This collapse of the RS era requires equating the mass scale m{sub α} of the GB modification and the mass scale m{sub σ} of the brane tension. However, if the GB contribution is to be considered as the lowest order correction from string theory to the RS action, we would expect m{sub α} > m{sub σ}. We investigate the effect upon the relic abundance of choosing more realistic values for the ratio R{sub m} ≡ m{sub α}/m{sub σ} and find that the relic abundance can be either enhanced or suppressed by more than two orders of magnitude. However, suppression only occurs for a small range of parameter choices and, overwhelmingly, the predominant situation is that of enhancement as we recover the usual Randall-Sundrum type behaviour in the limit R{sub m} >> 1. We use the latest observational bound Ω{sub DM}h{sup 2} = 0.1187 ± 0.0017 to constrain the various model parameters and briefly discuss the implications for direct/indirect dark matter detection experiments as well as dark matter particle models.

  19. Relate the earthquake parameters to the maximum tsunami runup

    Science.gov (United States)

    Sharghivand, Naeimeh; Kânoǧlu, Utku

    2016-04-01

    Considering the 1 September 1992 Nicaraguan tsunami manifested itself with an initial shoreline recession, there was paradigm shift from solitary wave to an N-wave (Tadepalli and Synolakis, 1994, Proc. R. Soc. A: Math. Phys. Eng. Sci., 445, 99-112) to define the initial waveform of tsunamis (Kanoglu et al., 2015, Phil. Trans. R. Soc. A, 373: 20140369). The N-wave initial waveform shows specific features, which might enhance maximum runup at a target coastline. Tadepalli & Synolakis (1994) showed that the leading depression N-wave (LEN) run up higher than its mirror image, the leading elevation N-wave (LEN). Later, Kanoglu et al. (2013, Proc. R. Soc. A: Math. Phys. Eng. Sci., 469, 20130015) considered two-dimensional propagation of a finite crest length N-wave over a flat bottom and showed that focusing effect of an N-wave in the direction of leading depression, which enhance the runup. Recently, Kanoglu (2016, EGU Abstract)'s preliminary results suggest that later waves could be higher on the leading depression side for an N-wave, i.e., sequencing defined by Okal and Synolakis (2016, Geophys. J. Int. 204, 719-735) is more pronounced on the leading depression side. Here, we consider submarine earthquakes and estimate the initial ocean surface profiles through Okada's formulation (1985, Bull. Seismol. Soc. Am. 75, 1135-1040). We parameterize earthquake source parameters, such as the length and the width of the fault, the focal depth, the rake (slip) and the dip angles, and the slip amount. Then, we relate ocean surface profiles calculated through Okada (1985) to the generalized N-wave profile defined by Tadepalli and Synolakis (1994) and identify N-wave parameters. Since, for an N-wave type initial condition, Tadepalli and Synolakis (1994) presented maximum runup for a canonical problem -wave propagating over a constant depth segment first and then over a sloping beach- and Kanoglu (2004, J. Fluid Mech., 513, 363-372) for a sloping beach their results allow us to

  20. Acute simvastatin inhibits K ATP channels of porcine coronary artery myocytes.

    Directory of Open Access Journals (Sweden)

    Sai Wang Seto

    Full Text Available BACKGROUND: Statins (3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA reductase inhibitors consumption provides beneficial effects on cardiovascular systems. However, effects of statins on vascular KATP channel gatings are unknown. METHODS: Pig left anterior descending coronary artery and human left internal mammary artery were isolated and endothelium-denuded for tension measurements and Western immunoblots. Enzymatically-dissociated/cultured arterial myocytes were used for patch-clamp electrophysiological studies and for [Ca(2+]i, [ATP]i and [glucose]o uptake measurements. RESULTS: The cromakalim (10 nM to 10 µM- and pinacidil (10 nM to 10 µM-induced concentration-dependent relaxation of porcine coronary artery was inhibited by simvastatin (3 and 10 µM. Simvastatin (1, 3 and 10 µM suppressed (in okadaic acid (10 nM-sensitive manner cromakalim (10 µM- and pinacidil (10 µM-mediated opening of whole-cell KATP channels of arterial myocytes. Simvastatin (10 µM and AICAR (1 mM elicited a time-dependent, compound C (1 µM-sensitive [(3H]-2-deoxy-glucose uptake and an increase in [ATP]i levels. A time (2-30 min- and concentration (0.1-10 µM-dependent increase by simvastatin of p-AMPKα-Thr(172 and p-PP2A-Tyr(307 expression was observed. The enhanced p-AMPKα-Thr(172 expression was inhibited by compound C, ryanodine (100 µM and KN93 (10 µM. Simvastatin-induced p-PP2A-Tyr(307 expression was suppressed by okadaic acid, compound C, ryanodine, KN93, phloridzin (1 mM, ouabain (10 µM, and in [glucose]o-free or [Na(+]o-free conditions. CONCLUSIONS: Simvastatin causes ryanodine-sensitive Ca(2+ release which is important for AMPKα-Thr(172 phosphorylation via Ca(2+/CaMK II. AMPKα-Thr(172 phosphorylation causes [glucose]o uptake (and an [ATP]i increase, closure of KATP channels, and phosphorylation of AMPKα-Thr(172 and PP2A-Tyr(307 resulted. Phosphorylation of PP2A-Tyr(307 occurs at a site downstream of AMPKα-Thr(172 phosphorylation.

  1. ERK1/2 map kinase metabolic pathway is responsible for phosphorylation of translation initiation factor eIF4E during in vitro maturation of pig oocytes.

    Science.gov (United States)

    Ellederová, Zdenka; Cais, Ondrej; Susor, Andrej; Uhlírová, Katka; Kovárová, Hana; Jelínková, Lucie; Tomek, Wolfgang; Kubelka, Michal

    2008-02-01

    Eukaryotic initiation factor 4E (eIF4E) plays an important role in mRNA translation by binding the 5'-cap structure of the mRNA and facilitating the recruitment to the mRNA of other translation factors and the 40S ribosomal subunit. eIF4E undergoes regulated phosphorylation on Ser-209 and this phosphorylation is believed to be important for its binding to mRNA and to other initiation factors. The findings showing that the translation initiation factor eIF4E becomes gradually phosphorylated during in vitro maturation (IVM) of pig oocytes with a maximum in metaphase II (M II) stage oocytes have been documented by us recently (Ellederova et al., 2006). The aim of this work was to study in details the metabolic pathways involved in this process. Using inhibitors of cyclin-dependent kinases, Butyrolactone I (BL I) and protein phosphatases, okadaic acid (OA) we show that ERK1/2 MAP kinase pathway is involved in this phosphorylation. We also demonstrate that activation and phosphorylation of ERK1/2 MAP kinase and eIF4E is associated with the activating phosphorylation of Mnk1 kinase, one of the two main kinases phosphorylating eIF4E in somatic cells.

  2. Study of Adsorption and Flocculation Properties of Natural Clays to Remove Prorocentrum lima.

    Science.gov (United States)

    Louzao, Maria Carmen; Abal, Paula; Fernández, Diego A; Vieytes, Mercedes R; Legido, José Luis; Gómez, Carmen P; Pais, Jesus; Botana, Luis M

    2015-09-29

    High accumulations of phytoplankton species that produce toxins are referred to as harmful algal blooms (HABs). HABs represent one of the most important sources of contamination in marine environments, as well as a serious threat to public health, fisheries, aquaculture-based industries, and tourism. Therefore, methods effectively controlling HABs with minimal impact on marine ecology are required. Marine dinoflagellates of the genera Dinophysis and Prorocentrum are representative producers of okadaic acid (OA) and dinophysistoxins responsible for the diarrhetic shellfish poisoning (DSP) which is a human intoxication caused by the consumption of shellfish that bioaccumulate those toxins. In this work we explore the use of natural clay for removing Prorocentrum lima. We evaluate the adsorption properties of clays in seawater containing the dinoflagellates. The experimental results confirmed the cell removal through the flocculation of algal and mineral particles leading to the formation of aggregates, which rapidly settle and further entrain cells during their descent. Moreover, the microscopy images of the samples enable one to observe the clays in aggregates of two or more cells where the mineral particles were bound to the outer membranes of the dinoflagellates. Therefore, this preliminary data offers promising results to use these clays for the mitigation of HABs.

  3. Propofol Anesthesia Is Reduced in Phospholipase C-Related Inactive Protein Type-1 Knockout Mice.

    Science.gov (United States)

    Nikaido, Yoshikazu; Furukawa, Tomonori; Shimoyama, Shuji; Yamada, Junko; Migita, Keisuke; Koga, Kohei; Kushikata, Tetsuya; Hirota, Kazuyoshi; Kanematsu, Takashi; Hirata, Masato; Ueno, Shinya

    2017-06-01

    The GABA type A receptor (GABAA-R) is a major target of intravenous anesthetics. Phospholipase C-related inactive protein type-1 (PRIP-1) is important in GABAA-R phosphorylation and membrane trafficking. In this study, we investigated the role of PRIP-1 in general anesthetic action. The anesthetic effects of propofol, etomidate, and pentobarbital were evaluated in wild-type and PRIP-1 knockout (PRIP-1 KO) mice by measuring the latency and duration of loss of righting reflex (LORR) and loss of tail-pinch withdrawal response (LTWR). The effect of pretreatment with okadaic acid (OA), a protein phosphatase 1/2A inhibitor, on propofol- and etomidate-induced LORR was also examined. PRIP-1 deficiency provided the reduction of LORR and LTWR induced by propofol but not by etomidate or pentobarbital, indicating that PRIP-1 could determine the potency of the anesthetic action of propofol. Pretreatment with OA recovered the anesthetic potency induced by propofol in PRIP-1 KO mice. OA injection enhanced phosphorylation of cortical the GABAA-R β3 subunit in PRIP-1 KO mice. These results suggest that PRIP-1-mediated GABAA-R β3 subunit phosphorylation might be involved in the general anesthetic action induced by propofol but not by etomidate or pentobarbital. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

  4. Vasoinhibins prevent retinal vasopermeability associated with diabetic retinopathy in rats via protein phosphatase 2A-dependent eNOS inactivation.

    Science.gov (United States)

    García, Celina; Aranda, Jorge; Arnold, Edith; Thébault, Stéphanie; Macotela, Yazmín; López-Casillas, Fernando; Mendoza, Valentín; Quiroz-Mercado, Hugo; Hernández-Montiel, Hebert Luis; Lin, Sue-Hwa; de la Escalera, Gonzalo Martínez; Clapp, Carmen

    2008-06-01

    Increased retinal vasopermeability contributes to diabetic retinopathy, the leading cause of blindness in working-age adults. Despite clinical progress, effective therapy remains a major need. Vasoinhibins, a family of peptides derived from the protein hormone prolactin (and inclusive of the 16-kDa fragment of prolactin), antagonize the proangiogenic effects of VEGF, a primary mediator of retinal vasopermeability. Here, we demonstrate what we believe to be a novel function of vasoinhibins as inhibitors of the increased retinal vasopermeability associated with diabetic retinopathy. Vasoinhibins inhibited VEGF-induced vasopermeability in bovine aortic and rat retinal capillary endothelial cells in vitro. In vivo, vasoinhibins blocked retinal vasopermeability in diabetic rats and in response to intravitreous injection of VEGF or of vitreous from patients with diabetic retinopathy. Inhibition by vasoinhibins was similar to that achieved following immunodepletion of VEGF from human diabetic retinopathy vitreous or blockage of NO synthesis, suggesting that vasoinhibins inhibit VEGF-induced NOS activation. We further showed that vasoinhibins activate protein phosphatase 2A (PP2A), leading to eNOS dephosphorylation at Ser1179 and, thereby, eNOS inactivation. Moreover, intravitreous injection of okadaic acid, a PP2A inhibitor, blocked the vasoinhibin effect on endothelial cell permeability and retinal vasopermeability. These results suggest that vasoinhibins have the potential to be developed as new therapeutic agents to control the excessive retinal vasopermeability observed in diabetic retinopathy and other vasoproliferative retinopathies.

  5. Vasoinhibins prevent retinal vasopermeability associated with diabetic retinopathy in rats via protein phosphatase 2A–dependent eNOS inactivation

    Science.gov (United States)

    García, Celina; Aranda, Jorge; Arnold, Edith; Thébault, Stéphanie; Macotela, Yazmín; López-Casillas, Fernando; Mendoza, Valentín; Quiroz-Mercado, Hugo; Hernández-Montiel, Hebert Luis; Lin, Sue-Hwa; de la Escalera, Gonzalo Martínez; Clapp, Carmen

    2008-01-01

    Increased retinal vasopermeability contributes to diabetic retinopathy, the leading cause of blindness in working-age adults. Despite clinical progress, effective therapy remains a major need. Vasoinhibins, a family of peptides derived from the protein hormone prolactin (and inclusive of the 16-kDa fragment of prolactin), antagonize the proangiogenic effects of VEGF, a primary mediator of retinal vasopermeability. Here, we demonstrate what we believe to be a novel function of vasoinhibins as inhibitors of the increased retinal vasopermeability associated with diabetic retinopathy. Vasoinhibins inhibited VEGF-induced vasopermeability in bovine aortic and rat retinal capillary endothelial cells in vitro. In vivo, vasoinhibins blocked retinal vasopermeability in diabetic rats and in response to intravitreous injection of VEGF or of vitreous from patients with diabetic retinopathy. Inhibition by vasoinhibins was similar to that achieved following immunodepletion of VEGF from human diabetic retinopathy vitreous or blockage of NO synthesis, suggesting that vasoinhibins inhibit VEGF-induced NOS activation. We further showed that vasoinhibins activate protein phosphatase 2A (PP2A), leading to eNOS dephosphorylation at Ser1179 and, thereby, eNOS inactivation. Moreover, intravitreous injection of okadaic acid, a PP2A inhibitor, blocked the vasoinhibin effect on endothelial cell permeability and retinal vasopermeability. These results suggest that vasoinhibins have the potential to be developed as new therapeutic agents to control the excessive retinal vasopermeability observed in diabetic retinopathy and other vasoproliferative retinopathies. PMID:18497878

  6. Ceramide inhibits PKCθ by regulating its phosphorylation and translocation to lipid rafts in Jurkat cells.

    Science.gov (United States)

    Hage-Sleiman, Rouba; Hamze, Asmaa B; El-Hed, Aimée F; Attieh, Randa; Kozhaya, Lina; Kabbani, Sarah; Dbaibo, Ghassan

    2016-08-01

    Protein kinase C theta (PKCθ) is a novel, calcium-independent member of the PKC family of kinases that was identified as a central player in T cell signaling and proliferation. Upon T cell activation by antigen-presenting cells, PKCθ gets phosphorylated and activated prior to its translocation to the immunological synapse where it couples with downstream effectors. PKCθ may be regulated by ceramide, a crucial sphingolipid that is known to promote differentiation, growth arrest, and apoptosis. To further investigate the mechanism, we stimulated human Jurkat T cells with either PMA or anti-CD3/anti-CD28 antibodies following induction of ceramide accumulation by adding exogenous ceramide, bacterial sphingomyelinase, or Fas ligation. Our results suggest that ceramide regulates the PKCθ pathway through preventing its critical threonine 538 (Thr538) phosphorylation and subsequent activation, thereby inhibiting the kinase's translocation to lipid rafts. Moreover, this inhibition is not likely to be a generic effect of ceramide on membrane reorganization. Other lipids, namely dihydroceramide, palmitate, and sphingosine, did not produce similar effects on PKCθ. Addition of the phosphatase inhibitors okadaic acid and calyculin A reversed the inhibition exerted by ceramide, and this suggests involvement of a ceramide-activated protein phosphatase. Such previously undescribed mechanism of regulation of PKCθ raises the possibility that ceramide, or one of its derivatives, and may prove valuable in novel therapeutic approaches for disorders involving autoimmunity or excessive inflammation-where PKCθ plays a critical role.

  7. Suggested Involvement of PP1/PP2A Activity and De Novo Gene Expression in Anhydrobiotic Survival in a Tardigrade, Hypsibius dujardini, by Chemical Genetic Approach.

    Directory of Open Access Journals (Sweden)

    Koyuki Kondo

    Full Text Available Upon desiccation, some tardigrades enter an ametabolic dehydrated state called anhydrobiosis and can survive a desiccated environment in this state. For successful transition to anhydrobiosis, some anhydrobiotic tardigrades require pre-incubation under high humidity conditions, a process called preconditioning, prior to exposure to severe desiccation. Although tardigrades are thought to prepare for transition to anhydrobiosis during preconditioning, the molecular mechanisms governing such processes remain unknown. In this study, we used chemical genetic approaches to elucidate the regulatory mechanisms of anhydrobiosis in the anhydrobiotic tardigrade, Hypsibius dujardini. We first demonstrated that inhibition of transcription or translation drastically impaired anhydrobiotic survival, suggesting that de novo gene expression is required for successful transition to anhydrobiosis in this tardigrade. We then screened 81 chemicals and identified 5 chemicals that significantly impaired anhydrobiotic survival after severe desiccation, in contrast to little or no effect on survival after high humidity exposure only. In particular, cantharidic acid, a selective inhibitor of protein phosphatase (PP 1 and PP2A, exhibited the most profound inhibitory effects. Another PP1/PP2A inhibitor, okadaic acid, also significantly and specifically impaired anhydrobiotic survival, suggesting that PP1/PP2A activity plays an important role for anhydrobiosis in this species. This is, to our knowledge, the first report of the required activities of signaling molecules for desiccation tolerance in tardigrades. The identified inhibitory chemicals could provide novel clues to elucidate the regulatory mechanisms underlying anhydrobiosis in tardigrades.

  8. Suggested Involvement of PP1/PP2A Activity and De Novo Gene Expression in Anhydrobiotic Survival in a Tardigrade, Hypsibius dujardini, by Chemical Genetic Approach.

    Science.gov (United States)

    Kondo, Koyuki; Kubo, Takeo; Kunieda, Takekazu

    2015-01-01

    Upon desiccation, some tardigrades enter an ametabolic dehydrated state called anhydrobiosis and can survive a desiccated environment in this state. For successful transition to anhydrobiosis, some anhydrobiotic tardigrades require pre-incubation under high humidity conditions, a process called preconditioning, prior to exposure to severe desiccation. Although tardigrades are thought to prepare for transition to anhydrobiosis during preconditioning, the molecular mechanisms governing such processes remain unknown. In this study, we used chemical genetic approaches to elucidate the regulatory mechanisms of anhydrobiosis in the anhydrobiotic tardigrade, Hypsibius dujardini. We first demonstrated that inhibition of transcription or translation drastically impaired anhydrobiotic survival, suggesting that de novo gene expression is required for successful transition to anhydrobiosis in this tardigrade. We then screened 81 chemicals and identified 5 chemicals that significantly impaired anhydrobiotic survival after severe desiccation, in contrast to little or no effect on survival after high humidity exposure only. In particular, cantharidic acid, a selective inhibitor of protein phosphatase (PP) 1 and PP2A, exhibited the most profound inhibitory effects. Another PP1/PP2A inhibitor, okadaic acid, also significantly and specifically impaired anhydrobiotic survival, suggesting that PP1/PP2A activity plays an important role for anhydrobiosis in this species. This is, to our knowledge, the first report of the required activities of signaling molecules for desiccation tolerance in tardigrades. The identified inhibitory chemicals could provide novel clues to elucidate the regulatory mechanisms underlying anhydrobiosis in tardigrades.

  9. Bayesian inference of earthquake parameters from buoy data using a polynomial chaos-based surrogate

    KAUST Repository

    Giraldi, Loic

    2017-04-07

    This work addresses the estimation of the parameters of an earthquake model by the consequent tsunami, with an application to the Chile 2010 event. We are particularly interested in the Bayesian inference of the location, the orientation, and the slip of an Okada-based model of the earthquake ocean floor displacement. The tsunami numerical model is based on the GeoClaw software while the observational data is provided by a single DARTⓇ buoy. We propose in this paper a methodology based on polynomial chaos expansion to construct a surrogate model of the wave height at the buoy location. A correlated noise model is first proposed in order to represent the discrepancy between the computational model and the data. This step is necessary, as a classical independent Gaussian noise is shown to be unsuitable for modeling the error, and to prevent convergence of the Markov Chain Monte Carlo sampler. Second, the polynomial chaos model is subsequently improved to handle the variability of the arrival time of the wave, using a preconditioned non-intrusive spectral method. Finally, the construction of a reduced model dedicated to Bayesian inference is proposed. Numerical results are presented and discussed.

  10. Radioimmunoassay for the teleocidins using 26 (2'-aminoethylthio)-tetrahydroteleocidin A-2 as hapten

    Energy Technology Data Exchange (ETDEWEB)

    Levine, L.; Gjika, H.B.; Vunakis, H. van; Fujiki, Hirota; Sakai, Shin-ichiro

    1988-09-01

    To obtain antibodies, 26 (2'-aminoethylthio)-tetrahydroteleocidin A-2 was covalently linked to bovine albumin with a carbodiimide and the resulting conjugate used for immunization of rabbits. Antibodies directed toward teleocidin were produced as measured by neutralization of teleocidin's capacity to stimulate arachidonic acid metabolism in rat liver cells (the C-9 cell line). An /sup 125/I-labeled ligand was prepared by reaction of the same derivative with radiolabeled Bolton-Hunter reagent. The antibodies bound this radiolabeled hapten, and the binding increased progressively with repeated immunizations. After absorption of the rabbit IgG with a goat anti-rabbit IgG, binding was reduced > 95%. The serologic specificity of the antiserum was characterized by measuring the inhibition of binding by several teleocidins of varying structure as well as by other tumor promoters and toxins. The rank order of inhibitory activity expressed as concentration required for 50% inhibition (IC/sub 50/) was for 26 (2'-aminoethylthio)-tetrahydroteleocidin A-2 (0.56 pmol) > teleocidin A-1 (6.5 pmol) greater than or equal to teleocidin A-2 (7.3 pmol) > (-)-indolactam-V (3.7 nmol) > teleocidin B-4 (13 nmol). Maitotoxin, aplysiatoxin, palytoxin, mezerein, okadaic acid and 12-O-tetradecanoylphorbol-13-acetate did not inhibit at the levels tested.

  11. Ultrafast superresolution fluorescence imaging with spinning disk confocal microscope optics.

    Science.gov (United States)

    Hayashi, Shinichi; Okada, Yasushi

    2015-05-01

    Most current superresolution (SR) microscope techniques surpass the diffraction limit at the expense of temporal resolution, compromising their applications to live-cell imaging. Here we describe a new SR fluorescence microscope based on confocal microscope optics, which we name the spinning disk superresolution microscope (SDSRM). Theoretically, the SDSRM is equivalent to a structured illumination microscope (SIM) and achieves a spatial resolution of 120 nm, double that of the diffraction limit of wide-field fluorescence microscopy. However, the SDSRM is 10 times faster than a conventional SIM because SR signals are recovered by optical demodulation through the stripe pattern of the disk. Therefore a single SR image requires only a single averaged image through the rotating disk. On the basis of this theory, we modified a commercial spinning disk confocal microscope. The improved resolution around 120 nm was confirmed with biological samples. The rapid dynamics of micro-tubules, mitochondria, lysosomes, and endosomes were observed with temporal resolutions of 30-100 frames/s. Because our method requires only small optical modifications, it will enable an easy upgrade from an existing spinning disk confocal to a SR microscope for live-cell imaging. © 2015 Hayashi and Okada. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  12. Common European harmful algal blooms affect the viability and innate immune responses of Mytilus edulis larvae.

    Science.gov (United States)

    De Rijcke, M; Vandegehuchte, M B; Vanden Bussche, J; Nevejan, N; Vanhaecke, L; De Schamphelaere, K A C; Janssen, C R

    2015-11-01

    Like marine diseases, harmful algal blooms (HABs) are globally increasing in frequency, severity and geographical scale. As a result, bivalves will have to face the combined threat of toxic algae and marine pathogens more frequently in the (near) future. These stressors combined may further affect the recruitment of ecologically and economically important bivalve species as HABs can affect the growth, viability and development of their larvae. To date, little is known on the specific effects of HABs on the innate immune system of bivalve larvae. This study therefore investigates whether two common harmful algae can influence the larval viability, development and immunological resilience of the blue mussel Mytilus edulis. Embryos of this model organism were exposed (48 h) to five densities of Pseudo-nitzschia multiseries or Prorocentrum lima cells. In addition, the effect of six concentrations of their respective toxins: domoic acid (DA) and okadaic acid (OA) were assessed. OA was found to significantly reduce larval protein phosphatase activity (p larval viability (p < 0.01) at concentrations as low as 37.8 μg l(-1). P. multiseries (1400 cells ml(-1)), P. lima (150 cells ml(-1)) and DA (dosed five times higher than typical environmental conditions i.e. 623.2 μg l(-1)) increased the phenoloxidase (PO) innate immune activity of the mussel larvae. These results suggest that the innate immune response of even the earliest life stages of bivalves is susceptible to the presence of HABs.

  13. Occurrence of lipophilic marine toxins in shellfish from Galicia (NW of Spain) and synergies among them.

    Science.gov (United States)

    Rodríguez, Laura P; González, Virginia; Martínez, Aníbal; Paz, Beatriz; Lago, Jorge; Cordeiro, Victoria; Blanco, Lucía; Vieites, Juan Manuel; Cabado, Ana G

    2015-03-25

    Lipophilic marine toxins pose a serious threat for consumers and an enormous economic problem for shellfish producers. Synergistic interaction among toxins may play an important role in the toxicity of shellfish and consequently in human intoxications. In order to study the toxic profile of molluscs, sampled during toxic episodes occurring in different locations in Galicia in 2014, shellfish were analyzed by liquid chromatography tandem mass spectrometry (LC-MS/MS), the official method for the detection of lipophilic toxins. The performance of this procedure was demonstrated to be fit for purpose and was validated in house following European guidelines. The vast majority of toxins present in shellfish belonged to the okadaic acid (OA) group and some samples from a particular area contained yessotoxin (YTX). Since these toxins occur very often with other lipophilic toxins, we evaluated the potential interactions among them. A human neuroblastoma cell line was used to study the possible synergies of OA with other lipophilic toxins. Results show that combination of OA with dinophysistoxin 2 (DTX2) or YTX enhances the toxicity triggered by OA, decreasing cell viability and cell proliferation, depending on the toxin concentration and incubation time. The effects of other lipophilic toxins as 13-desmethyl Spirolide C were also evaluated in vitro.

  14. Gli spazi di negoziazione dell'appartenenza religiosa in Sukyo Mahikari: un'analisi etnografica

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    Andrea Molle

    2009-04-01

    Full Text Available Sukyo Mahikari (nel prosieguo Mahikari è un nuovo movimento religioso non buddhista che ha origine dal Sekai Mahikari Bunmei Kyodan, fondato in Giappone da Okada Yoshikazu nel 1963. Il centro della dottrina e delle attività di Mahikari è il rituale di purificazione detto di ‘trasmissione della luce divina’ (okiyome, mentre il nome stesso del movimento sottintende la sua natura di organizzazione dedita alla trasmissione della ‘vera luce’ (ma hikari e alla diffusione di insegnamenti sovra religiosi (sukyo. Registrando un tasso di crescita relativamente elevato (saldo netto tra iniziazioni e uscite registrate, Mahikari viene oggi considerato dagli studiosi un nuovo movimento religioso giapponese tra i più interessanti. In Italia il movimento è presente dal 1974, a seguito dell'apertura di un primo centro di pratica (dojo nella città di Milano. I centri di pratica aderenti alla Federazione Italiana Sukyo Mahikari si concentrano maggiormente in Lombardia e in Veneto, ma con buoni tassi di crescita anche nelle altre regioni. La mia ricerca etnografica, della durata complessiva tre anni e svolta prevalentemente nei centri di Milano, Lussemburgo e Takayama (Giappone, si è concentrata sull'analisi di quegli elementi organizzativi del sistema simbolico di Mahikari che garantiscono l'integrazione del movimento in diversi contesti geografici nonostante lo spiccato esotismo delle sue dottrine.

  15. 蛋白磷酸酯酶-1和-2A抑制剂对NG108-15细胞tau蛋白磷酸化的影响%EFFECT OF PROTEIN PHOSPHATASE-1 AND 2A INHIBITOR ON TAU PROTEIN PHOSPHORYLATION OF NG108-14 CELL

    Institute of Scientific and Technical Information of China (English)

    朱粹青; 曹小定

    2002-01-01

    Alzheimer痴呆(AD)的主要脑病理变化之一为由超磷酸化的tau蛋白组成的神经原纤维缠结(Neurofibrillary tangle,NFT).AD的Tau蛋白异常磷酸化与蛋白磷酸酯酶(PP)-2A和-1缺陷有关.本文首先用免疫印迹法显示NG含两大组分的tau蛋白.MTT方法观察到PP-2A和PP-1抑制剂冈田酸(Okadaic acid,OA)处理NG108-14细胞能导致细胞代谢明显下降,同时免疫印迹法显示OA能导致的NG细胞Tau蛋白磷酸化.该研究为建立AD样蛋白磷酸酯酶缺陷引起的tau蛋白磷酸化的细胞模型奠定了基础.

  16. The key molecular events during Macrobrachium rosenbergii nodavirus (MrNV) infection and replication in Sf9 insect cells.

    Science.gov (United States)

    Somrit, Monsicha; Watthammawut, Atthaboon; Chotwiwatthanakun, Charoonroj; Weerachatyanukul, Wattana

    2016-09-02

    In this study we demonstrated that Macrobrachium rosenbergii nodavirus (MrNV) was able to internalize and replicate in Sf9 insect cells, with levels of infection altered by substances affecting the caveolin-(CAV) mediated endocytosis pathway. The use of Sf9 cells for efficient MrNV replication and propagation was demonstrated by confocal microscopy and PCR amplification, through which early viral binding and internalization were initially detectable at 30min post-infection; whereas at 72h, the distinguishable sign of late-MrNV infection was observable as the gradual accumulation of a cytopathic effect (CPE) in the cells, ultimately resulting in cellular disruption. Moreover, during the early period of infection, the MrNV signals were highly co-localized with CAV1 signals of the CAV-mediated endocytosis pathway. The use of genistein as an inhibitor of the CAV-mediated endocytosis pathway significantly reduced MrNV and CAV1 co-localization, and also reduced the levels of MrNV infection in Sf9 cells as shown by PCR and ELISA. Moreover, the addition of the pathway agonist okadaic acid not only recovered but also augmented both the levels of MrNV co-localization with CAV1 and of Sf9 infection in the presence of genistein inhibition; therefore demonstrating that MrNV infection in Sf9 cells was associated with the CAV-mediated endocytosis pathway machinery.

  17. Preparation of anti-ciguatoxin monoclonal antibodies using synthetic haptens: sandwich ELISA detection of ciguatoxins.

    Science.gov (United States)

    Tsumuraya, Takeshi; Fujii, Ikuo; Hirama, Masahiro

    2014-01-01

    Ciguatera fish poisoning (CFP) is a form of food poisoning caused by the consumption of fish that have accumulated a type of sodium channel activator toxin called ciguatoxins (CTXs), which are produced by dinoflagellates of the genus Gambierdiscus through the food chain. CFP affects more than 50000 people each year. The extremely low level of CTXs in tainted fish has hampered the development of antibodies for the detection of these toxins. Monoclonal antibodies (mAbs) specific against major congeners of CTX3C, 51-hydroxyCTX3C, CTX1B, and 54-deoxyCTX1B were prepared by immunization of mice with protein conjugates of rationally designed synthetic haptens in place of the natural toxins. We found that haptenic groups possessing a surface area larger than 400 angstroms2 were required to produce mAbs that can bind strongly to CTXs. Direct sandwich ELISA utilizing two different monoclonal antibodies that bind specifically to one of the two wings of a CTX were established to detect CTXs. No cross-reactivity was observed against the other marine toxins tested, including brevetoxin A, brevetoxin B, okadaic acid, and maitotoxin.

  18. Application of Hectorite-Coated Silica Gel Particles as a Packing Material for Chromatographic Resolution.

    Science.gov (United States)

    Okada, Tomohiko; Kumasaki, Aisaku; Shimizu, Kei; Yamagishi, Akihiko; Sato, Hisako

    2016-08-01

    A new type of clay column particles was prepared, in which a hectorite layer (∼0.1 µm thickness) covered uniformly the surface of amorphous silica particles with an average radius of 5 µm (ref. Okada et al., The Journal of Physical Chemistry C, 116, 21864-21869 (2012)). The hectorite layer was fully ion-exchanged with Δ-[Ru(phen)3](2+) (phen = 1,10-phenanthroline) ions by being immersed in a methanol solution of Δ-[Ru(phen)3](ClO4)2 (1 mM). The modified silica gel particles thus prepared were packed into a stainless steel tube (4 mm (i.d.) × 25 cm) as a high-performance liquid chromatography column. Optical resolution was achieved when the racemic mixtures of several metal complexes or organic molecules were eluted with methanol. In the case of tris(acetylacetonato)ruthenium(III) ([Ru(acac)3]), for example, the Λ- and Δ-enantiomers gave an elution volume of 2.6 and 3.0 mL, respectively, with the separation factor of 1.2. The total elution volume (5 mL) was nearly one-tenth for the previously reported column of the same size (RU-1 (Shiseido Co., Ltd.)) packed with the spray-dried particles of synthetic hectorite (average radius 5 µm) ion-exchanged by the same Ru(II) complexes.

  19. Global coseismic deformations, GNSS time series analysis, and earthquake scaling laws

    Science.gov (United States)

    Métivier, Laurent; Collilieux, Xavier; Lercier, Daphné; Altamimi, Zuheir; Beauducel, François

    2014-12-01

    We investigate how two decades of coseismic deformations affect time series of GPS station coordinates (Global Navigation Satellite System) and what constraints geodetic observations give on earthquake scaling laws. We developed a simple but rapid model for coseismic deformations, assuming different earthquake scaling relations, that we systematically applied on earthquakes with magnitude larger than 4. We found that coseismic displacements accumulated during the last two decades can be larger than 10 m locally and that the cumulative displacement is not only due to large earthquakes but also to the accumulation of many small motions induced by smaller earthquakes. Then, investigating a global network of GPS stations, we demonstrate that a systematic global modeling of coseismic deformations helps greatly to detect discontinuities in GPS coordinate time series, which are still today one of the major sources of error in terrestrial reference frame construction (e.g., the International Terrestrial Reference Frame). We show that numerous discontinuities induced by earthquakes are too small to be visually detected because of seasonal variations and GPS noise that disturb their identification. However, not taking these discontinuities into account has a large impact on the station velocity estimation, considering today's precision requirements. Finally, six groups of earthquake scaling laws were tested. Comparisons with our GPS time series analysis on dedicated earthquakes give insights on the consistency of these scaling laws with geodetic observations and Okada coseismic approach.

  20. Dinophysis caudata generated lipophilic shellfish toxins in bivalves from the Nanji Islands, East China Sea

    Science.gov (United States)

    Jiang, Tao; Xu, Yixiao; Li, Yang; Qi, Yuzao; Jiang, Tianjiu; Wu, Feng; Zhang, Fan

    2014-01-01

    A 12-month program of monitoring potentially toxic microalgae (that produce lipophilic shellfish toxins; LSTs) and their toxins in bivalves was conducted from April 2006 to March 2007 in the Nanji Islands, East China Sea. Two Dinophysis species, D. caudata and D. acuminata, were identified, and D. caudata was found to be the dominant species. D. caudata was detected in water samples between April and June 2006, and between February and March 2007. It reached its highest abundances in May, with a mean abundance of 1.38×102 cells/L in surface water and 1.25×102 cells/L in bottom water (cultured bivalves sampled between April and June were contaminated with LSTs, with an average toxicity of 85 μg okadaic acid (OA) eq./100 g meat, which was four times higher than the Chinese regulatory limit (20 μg OA eq./100 g meat). Ten out of fifteen wild samples (66.7%) collected during the same period were positive for LSTs, and contained an average LST toxicity of 45 μg OA eq./100 g meat (more than twice the regulatory value). Cultured Patinopecten yessoensis collected on 15 May 2006 had the highest toxicity, 320 μg OA eq./100 g meat, and relatively high toxicities (80 to 160 μg OA eq./100 g meat) were found in bivalves until the end of July.

  1. Occurrence of diarrhetic shellfish poisoning (DSP) toxins in clams (Ruditapes decussatus) from Tunis north lagoon.

    Science.gov (United States)

    Armi, Zina; Turki, Souad; Trabelsi, Elbahri; Ceredi, Alfiero; Riccardi, Elena; Milandri, Anna

    2012-08-01

    The main diarrhetic shellfish toxins, okadaic acid (OA) and dinophysistoxin-1, 2 (DTX-2, 2) were detected by liquid chromatography-tandem mass spectrometry (LC-MS/MS) as pyrenacyl esters in clams (Ruditapes decussatus) collected in Tunis north lagoon from January 2007 to June 2008. Sample analyses by LC-MS/MS displayed OA and related congeners (DTX-2, 2) with a highest detected level of 21 μg OA eq/kg shellfish meat for the samples of January 2007. Nevertheless, all samples were MBA negative. During the study period, potentially toxic dinoflagellate Dinophysis sacculus was recorded all year, blooming at different times. Highest concentrations were recorded during January 2007 with 4.6 × 10(4) cells per liter and 4.10(4) cells per liter in the northern and southern districts, respectively. Results show that there is no significant correlation between D. sacculus densities in water column and diarrhetic shellfish poisoning (DSP) toxins concentrations unregistered in clams. These data reveal that DSP toxicity in clams of Tunis north lagoon is low according to European regulatory limit (160 μg OA eq/kg shellfish meat). However, a potential threat, in this area, is represented by DSP toxic species as D. sacculus and provides grounds for widen and reinforcing sanitary control of the phycotoxin measures in the region.

  2. Lipophilic toxin profile in Mytilus galloprovincialis during episodes of diarrhetic shellfish poisoning (DSP) in the N.E. Adriatic Sea in 2006.

    Science.gov (United States)

    Nincevic Gladan, Zivana; Ujevic, Ivana; Milandri, Anna; Marasovic, Ivona; Ceredi, Alfiero; Pigozzi, Silvia; Arapov, Jasna; Skejic, Sanda

    2011-01-21

    Dinophysis spp. blooms and related shellfish toxicity events of diarrhetic shellfish poisoning (DSP) have been the most reported toxicity event through the Croatian National monitoring program. With the aim to characterize the DSP toxin profile in shellfish farmed in Croatia, for the first time a complete analysis of the toxin profile of Croatian mussels has been carried out using the LC-MS/MS technique. The obtained results showed okadaic acid (OA) as the main toxin contaminating Croatian mussels at that time. The maximum concentration of OA in shellfish tissue was recorded 12 days after the Dinophysis fortii bloom, thus suggesting that rapid growth of the toxin level in the shellfish occurred in the first week after the bloom while it was slower in the second week. Furthermore, the presence of only OA at concentrations which could endanger human health suggests D. fortii as the main organism responsible for the toxic event that occurred in Lim Bay. The presence of gymnodimine and spirolides in Croatian mussel has been detected for the first time, while the presence of yessotoxin and pectenotoxin-2 is confirmed.

  3. Acute Cardiotoxicity Evaluation of the Marine Biotoxins OA, DTX-1 and YTX

    Directory of Open Access Journals (Sweden)

    Sara F. Ferreiro

    2015-03-01

    Full Text Available Phycotoxins are marine toxins produced by phytoplankton that can get accumulated in filter feeding shellfish. Human intoxication episodes occur due to contaminated seafood consumption. Okadaic acid (OA and dynophysistoxins (DTXs are phycotoxins responsible for a severe gastrointestinal syndrome called diarrheic shellfish poisoning (DSP. Yessotoxins (YTXs are marine toxins initially included in the DSP class but currently classified as a separated group. Food safety authorities from several countries have regulated the content of DSPs and YTXs in shellfish to protect human health. In mice, OA and YTX have been associated with ultrastructural heart damage in vivo. Therefore, this study explored the potential of OA, DTX-1 and YTX to cause acute heart toxicity. Cardiotoxicity was evaluated in vitro by measuring hERG (human èter-a-go-go gene channel activity and in vivo using electrocardiogram (ECG recordings and cardiac damage biomarkers. The results demonstrated that these toxins do not exert acute effects on hERG channel activity. Additionally, in vivo experiments showed that these compounds do not alter cardiac biomarkers and ECG in rats acutely. Despite the ultrastructural damage to the heart reported for these toxins, no acute alterations of heart function have been detected in vivo, suggesting a functional compensation in the short term.

  4. Distribution of Marine Lipophilic Toxins in Shellfish Products Collected from the Chinese Market

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    Haiyan Wu

    2015-07-01

    Full Text Available To investigate the prevalence of lipophilic marine biotoxins in shellfish from the Chinese market, we used hydrophilic interaction liquid chromatography-tandem mass spectrometry (LC-MS/MS to measure levels of okadaic acid (OA, azaspiracid (AZA1, pectenotoxin (PTX2, gymnodimine (GYM, and spirolide (SPX1. We collected and analyzed 291 shellfish samples from main production sites along a wide latitudinal transect along the Chinese coastline from December 2008 to December 2009. Results revealed a patchy distribution of the five toxins and highlighted the specific geographical distribution and seasonal and species variation of the putative toxigenic organisms. All five lipophilic marine biotoxins were found in shellfish samples. The highest concentrations of OA, AZA1, PTX2, GYM, and SPX1 were 37.3, 5.90, 16.4, 14.4, and 8.97 μg/kg, respectively. These values were much lower than the legislation limits for lipophilic shellfish toxins. However, the value might be significantly underestimated for the limited detection toxins. Also, these toxins were found in most coastal areas of China and were present in almost all seasons of the year. Thus, these five toxins represent a potential threat to human health. Consequently, studies should be conducted and measures should be taken to ensure the safety of the harvested product.

  5. Aβ induces acute depression of excitatory glutamatergic synaptic transmission through distinct phosphatase-dependent mechanisms in rat CA1 pyramidal neurons.

    Science.gov (United States)

    Yao, Wen; Zou, Hao-Jun; Sun, Da; Ren, Si-Qiang

    2013-06-17

    Beta-amyloid peptide (Aβ) has a causal role in the pathophysiology of Alzheimer's disease (AD). Recent studies indicate that Aβ can disrupt excitatory glutamatergic synaptic function at synaptic level. However, the underlying mechanisms remain obscure. In this study, we recorded evoked and spontaneous EPSCs in hippocampal CA1 pyramidal neurons via whole-cell voltage-clamping methods and found that 1 μM Aβ can induce acute depression of basal glutamatergic synaptic transmission through both presynaptic and postsynaptic dysfunction. Moreover, we also found that Aβ-induced both presynaptic and postsynaptic dysfunction can be reversed by the inhibitor of protein phosphatase 2B (PP2B), FK506, whereas only postsynaptic disruption can be ameliorated by the inhibitor of PP1/PP2A, Okadaic acid (OA). These results indicate that PP1/PP2A and PP2B have overlapping but not identical functions in Aβ-induced acute depression of excitatory glutamatergic synaptic transmission of hippocampal CA1 pyramidal neurons.

  6. Identification and Biochemical Characterization of Protein Phosphatase 5 from the Cantharidin-Producing Blister Beetle, Epicauta chinensis

    Directory of Open Access Journals (Sweden)

    Xi'en Chen

    2013-12-01

    Full Text Available Protein phosphatase 5 (PP5 is a unique member of serine/threonine phosphatases which has been recognized in regulation of diverse cellular processes. A cDNA fragment encoding PP5 (EcPP5 was cloned and characterized from the cantharidin-producing blister beetle, E. chinensis. EcPP5 contains an open reading frame of 1500 bp that encodes a protein of 56.89 kDa. The deduced amino acid sequence shares 88% and 68% identities to the PP5 of Tribolium castaneum and humans, respectively. Analysis of the primary sequence shows that EcPP5 has three TPR (tetratricopeptide repeat motifs at its N-terminal region and contains a highly conserved C-terminal catalytic domain. RT-PCR reveals that EcPP5 is expressed in all developmental stages and in different tissues. The recombinant EcPP5 (rEcPP5 was produced in Escherichia coli and purified to homogeneity. The purified protein exhibited phosphatase activity towards pNPP (p-nitrophenyl phosphate and phosphopeptides, and its activity can be enhanced by arachidonic acid. In vitro inhibition study revealed that protein phosphatase inhibitors, okadaic acid, cantharidin, norcantharidin and endothall, inhibited its activity. Further, protein phosphatase activity of total soluble protein extract from E. chinensis adults could be impeded by these inhibitors suggesting there might be some mechanism to protect this beetle from being damaged by its self-produced cantharidin.

  7. Zanthoxylum avicennae extracts induce cell apoptosis through protein phosphatase 2A activation in HA22T human hepatocellular carcinoma cells and block tumor growth in xenografted nude mice.

    Science.gov (United States)

    Dung, Tran Duc; Chang, Hsien-Cheh; Chen, Chung-Yu; Peng, Wen-Huang; Tsai, Chang-Hai; Tsai, Fuu-Jen; Kuo, Wei-Wen; Chen, Li-Mien; Huang, Chih-Yang

    2011-12-01

    The use of herbs as alternative cancer therapies has attracted a great deal of attention owing to their lower toxicity. Whether Zanthoxylum avicennae (Ying Bu Bo, YBB) induces liver cancer cell apoptosis remains unclear. In this study, we investigated the effect of YBB extracts (YBBEs) on HA22T human hepatocellular carcinoma cells in vitro and in an in vivo mouse xenograft model. HA22T cells were treated with different concentrations of YBBEs and analyzed with Western blot analysis, TUNEL, JC-1 staining and siRNA transfection assays. Additionally, the HA22T-implanted xenograft nude mice model was applied to confirm the cellular effects. YBBEs-induced apoptosis, up-regulated death receptor apoptotic pathway markers as well as mitochondrial proteins, and suppressed the survival proteins in a dose-dependent manner. Pro-survival Bcl-2 family proteins were inhibited and the pro-apoptotic ones were increased. Protein phosphatase 2A (PP2A) siRNA or okadaic acid reversed the YBBEs effects, confirming the role of PP2A in YBBEs-induced HA22T apoptosis. All our experimental evidence indicates that YBBEs significantly promote HA22T apoptosis and reduce tumor sizes in xenograft nude mice via PP2A in a dose-dependent manner.

  8. Effect of seawater salinity on pore-size distribution on a poly(styrene)-based HP20 resin and its adsorption of diarrhetic shellfish toxins.

    Science.gov (United States)

    Fan, Lin; Sun, Geng; Qiu, Jiangbing; Ma, Qimin; Hess, Philipp; Li, Aifeng

    2014-12-19

    In the present study, okadaic acid (OA) and dinophysistoxin-1 (DTX1) were spiked into artificial seawater at low, medium and high estuarine salinities (9‰, 13.5‰ and 27‰). Passive samplers (HP20 resin) used for solid phase adsorption toxin tracking (SPATT) technology were exposed in these seawaters for 12-h periods. Adsorption curves well fitted a pseudo-secondary kinetics model. The highest initial sorption rates of both toxins occurred in the seawater of medium salinity, followed by seawater of low and high estuarine salinity. Pore volumes of micropores (salinity but not in seawater at medium salinity, which demonstrated that the toxin molecules entered into micropores and mesopores (below 10nm in size) in seawaters of high and low salinity. More toxin or other matrix agglomerates were displayed on the surface of resin deployed in the seawater of medium salinity. Taking into consideration the pore-size distribution and surface images, it appears that intra-particle diffusion governs toxin adsorption in seawater at high salinity while film diffusion mainly controls the adsorption process in seawater at medium salinity. This is the first study to confirm that molecules of OA and DTX1 are able to enter into micropores (salinity (∼27‰).

  9. Distinct regulation of activity-dependent transcription of immediate early genes in cultured rat cortical neurons.

    Science.gov (United States)

    Fukuchi, Mamoru; Sanabe, Tomofumi; Watanabe, Toshifumi; Kubota, Takane; Tabuchi, Akiko; Tsuda, Masaaki

    2017-08-26

    The activity-regulated expression of immediate early genes (IEGs) contributes to long-lasting neuronal functions underlying long-term memory. However, their response properties following neuronal activity are unique and remain poorly understood. To address this knowledge gap, here we further investigated the response properties of two representative IEGs, c-fos and brain-derived neurotrophic factor (Bdnf). Treatment of cultured cortical cells with KCl produces a depolarization process that results in the increase of intracellular calcium concentration in a KCl concentration-dependent manner. Consistent with this increase, c-fos expression was induced in a KCl concentration-dependent manner. In contrast, however, Bdnf expression was optimally activated by both 25 and 50 mM concentration of KCl. Similar results were observed when the cells were treated with okadaic acid, which inhibits protein phosphatases and elicits the hyper-phosphorylation of signaling molecules. Thus, Bdnf expression is strictly regulated by a neuronal activity threshold in an all or nothing manner, whereas c-fos expression is activated in a neuronal activity-dependent manner. Our findings also suggest that these differential responses might be due to the presence or absence of a TATA box. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. SCOP/PHLPP and its functional role in the brain.

    Science.gov (United States)

    Shimizu, Kimiko; Mackenzie, Scott M; Storm, Daniel R

    2010-01-01

    SCOP (suprachiasmatic nucleus (SCN) circadian oscillatory protein) was originally identified in 1999 in a differential display screen of the rat SCN for genes whose expression were regulated in a circadian manner (K. Shimizu, M. Okada, A. Takano and K. Nagai, FEBS Lett., 1999, 458, 363-369). The SCN is the principle pacemaker of the circadian clock, and expression of SCOP protein in the SCN was found to oscillate, increasing during the subjective night, even when animals were housed in constant darkness. SCOP interacts with and inhibits multiple proteins important for intracellular signaling, either by directly binding to K-Ras or by dephosphorylating p-Akt and p-PKC. Since the functions of K-Ras, Akt, and PKC are considerably divergent, SCOP may have several roles. We recently discovered that SCOP participates in the formation of long-term hippocampus-dependent memories, and other investigators have examined its role in cell proliferation and survival. In this review, we introduce SCOP from its molecular structure to its physiological functions, focusing mainly on its role in ERK1/2 activation and memory consolidation.

  11. Persistent Contamination of Octopuses and Mussels with Lipophilic Shellfish Toxins during Spring Dinophysis Blooms in a Subtropical Estuary

    Directory of Open Access Journals (Sweden)

    Luiz L. Mafra

    2015-06-01

    Full Text Available This study investigates the occurrence of diarrhetic shellfish toxins (DSTs and their producing phytoplankton species in southern Brazil, as well as the potential for toxin accumulation in co-occurring mussels (Perna perna and octopuses (Octopus vulgaris. During the spring in 2012 and 2013, cells of Dinophysis acuminata complex were always present, sometimes at relatively high abundances (max. 1143 cells L−1, likely the main source of okadaic acid (OA in the plankton (max. 34 ng L−1. Dinophysis caudata occurred at lower cell densities in 2013 when the lipophilic toxins pectenotoxin-2 (PTX-2 and PTX-2 seco acid were detected in plankton and mussel samples. Here, we report for the first time the accumulation of DSTs in octopuses, probably linked to the consumption of contaminated bivalves. Perna perna mussels were consistently contaminated with different DSTs (max. 42 µg kg−1, and all octopuses analyzed (n = 5 accumulated OA in different organs/tissues: digestive glands (DGs > arms > gills > kidneys > stomach + intestine. Additionally, similar concentrations of 7-O-palmytoyl OA and 7-O-palmytoly dinophysistoxin-1 (DTX-1 were frequently detected in the hepatopancreas of P. perna and DGs of O. vulgaris. Therefore, octopuses can be considered a potential vector of DSTs to both humans and top predators such as marine mammals.

  12. [Can solar/geomagnetic activity restrict the occurrence of some shellfish poisoning outbreaks? The example of PSP caused by Gymnodinium catenatum at the Atlantic Portuguese coast].

    Science.gov (United States)

    Vale, P

    2013-01-01

    Cyclic outbreaks of accumulation of paralytic shellfish poisoning (PSP) toxins in mussels attributed to Gymnodinium catenatum blooms displayed several of the highest inter-annual maxima coincidental with minima of the 11-year solar sunspot number (SSN) cycle. The monthly distribution of PSP was associated with low levels of the solar radio flux, a more quantitative approach than SSN for fluctuations in solar activity. A comparison between monthly distribution of PSP and other common biotoxins (okadaic acid (OA), dinophysistoxin-2 (DTX2) and amnesic shellfish poisoning (ASP) toxins) demonstrated that only PSP was significantly associated with low levels of radio flux (p radiation associated with the seasonal change in solar declination, and might play an additional role in seasonal signal-triggering. PSP distribution was also associated with low levels of the geomagnetic index Aa. A comparison between monthly distribution of PSP and other common biotoxins, also demonstrated that only PSP was significantly associated with low levels of the Aa index (p < 0.01). In some years of SSN minima no significant PSP-outbreaks in mussels were detected. This was attributed to a steady rise in geomagnetic activity that could disrupt the triggering signal. Global distribution patterns show that hotspots for G. catenatum blooms are regions with deficient crustal magnetic anomalies. In addition to the variable magnetic field mostly of solar origin, static fields related to magnetized rocks in the crust and upper mantle might play a role in restricting worldwide geographic distribution.

  13. A modality-specific neuromagnetic P3

    Energy Technology Data Exchange (ETDEWEB)

    Flynn, E.R.; Lewine, J.D.; Oakley, M.T.; Roeder, S.B.; Arthur, D.L.; Aine, C.J.; George, J.S.

    1989-01-01

    Several studies indicate that in cases of psychopathology and alcoholism the amplitude and/or latency of endogenous, scalp-recorded P3 potentials elicited by rare events are abnormal. The P3 complex may normally be a valuable index of the brain's work-load and identification of the neural generator(s) of this late positive component would thus provide valuable insight into the substrates of both normal and abnormal information processes. Okada and his colleagues have recorded magnetic field correlates of P3 potentials evoked by visual and auditory stimuli. Data from a mapping study of a visually evoked magnetic P3 were consistent with a hippocampal source, but attempts to localize the generator(s) of the auditory magnetic P3 were unsuccessful. In an effort to independently confirm, extend, and clarify these results, the surface topographies of magnetic P3-like complexes evoked during the performance of auditory and visual detection tasks were examined. 6 refs., 2 figs.

  14. Glucose-induced binding of the polypyrimidine tract-binding protein (PTB) to the 3'-untranslated region of the insulin mRNA (ins-PRS) is inhibited by rapamycin.

    Science.gov (United States)

    Tillmar, Linda; Welsh, Nils

    2004-05-01

    Despite considerable knowledge on the regulation of insulin gene transcription, little is known about the post-transcriptional control mechanisms of this gene. We have recently reported glucose- and hypoxia-regulated binding of the polypyrimidine tract-binding protein (PTB) to the pyrimidine-rich sequence of the 3'-untranslated insulin mRNA (ins-PRS), an event which may control insulin mRNA stability. The present aim was to probe for the signaling pathways that control this binding activity. Rat islets were exposed to pharmacological inhibitors against several molecules, previously shown to be involved in glucose signaling. The inhibitors used were; LY 294002 (PI3 kinase), Rp-cAMP triatylamine (the cAMP-dependent protein kinase PKA), bisindolylmaleimide I hydrochloride (PKC), PD 098059 (ERK1/ERK2), SB 203580 (p38/SAPK2a), rapamycin (mTOR) and okadaic acid (PP1/2A). PTB-binding activity to the ins-PRS was then analyzed by elecrophoretic mobility shift assay (EMSA). The glucose-induced PTB-binding was only inhibited by the mTOR inhibitor rapamycin. Rapamycin also reduced glucose-induced insulin mRNA expression. Thus, our results suggest an involvement of mTOR in glucose-induced PTB/ins-PRS binding and insulin mRNA stability.

  15. Masoprocol decreases rat lipolytic activity by decreasing the phosphorylation of HSL.

    Science.gov (United States)

    Gowri, M S; Azhar, R K; Kraemer, F B; Reaven, G M; Azhar, S

    2000-09-01

    Masoprocol (nordihydroguaiaretic acid), a lipoxygenase inhibitor isolated from the creosote bush, has been shown to decrease adipose tissue lipolytic activity both in vivo and in vitro. The present study was initiated to test the hypothesis that the decrease in lipolytic activity by masoprocol resulted from modulation of adipose tissue hormone-sensitive lipase (HSL) activity. The results indicate that oral administration of masoprocol to rats with fructose-induced hypertriglyceridemia significantly decreased their serum free fatty acid (FFA; P HSL activity were significantly lower (P HSL protein. Incubation of masoprocol with adipocytes from chow-fed rats significantly inhibited isoproterenol-induced lipolytic activity and HSL activity, associated with a decrease in the ability of isoproterenol to phosphorylate HSL. Masoprocol had no apparent effect on adipose tissue phosphatidylinositol 3-kinase activity, but okadaic acid, a serine/threonine phosphatase inhibitor, blocked the antilipolytic effect of masoprocol. The results of these in vitro and in vivo experiments suggest that the antilipolytic activity of masoprocol is secondary to its ability to inhibit HSL phosphorylation, possibly by increasing phosphatase activity. As a consequence, masoprocol administration results in lower serum FFA and TG concentrations in hypertriglyceridemic rodents.

  16. Theoretical and experimental investigations of electron emission in C{sup 6+} + H{sub 2}O collisions

    Energy Technology Data Exchange (ETDEWEB)

    Dal Cappello, C. [Universite Paul Verlaine-Metz, Laboratoire de Physique Moleculaire et des Collisions (LPMC), Institut Jean Barriol (FR2843), Institut de Physique de Metz, 1 Boulevard Arago, 57078 Metz Cedex 3 (France); Champion, C. [Universite Paul Verlaine-Metz, Laboratoire de Physique Moleculaire et des Collisions (LPMC), Institut Jean Barriol (FR2843), Institut de Physique de Metz, 1 Boulevard Arago, 57078 Metz Cedex 3 (France)], E-mail: champion@univ-metz.fr; Boudrioua, O.; Lekadir, H. [Universite Paul Verlaine-Metz, Laboratoire de Physique Moleculaire et des Collisions (LPMC), Institut Jean Barriol (FR2843), Institut de Physique de Metz, 1 Boulevard Arago, 57078 Metz Cedex 3 (France); Sato, Y. [Gunma University, Research Center for Heavy-Ion Medicine, Gunma (Japan); Ohsawa, D. [Kyoto University, Radioisotope Research Center, Kyoto (Japan)

    2009-03-15

    Theoretical differential and total cross sections for the direct ionization process of water vapour by 6 MeV/u C{sup 6+} ions are compared to new experimental measurements performed by the dedicated apparatus already used for measuring the energy and angular distributions of secondary electrons emitted from water vapour by fast heavy-ion impact [D. Ohsawa, H. Kawauchi, M. Hirabayashi, Y. Okada, T. Homma, A. Higashi, S. Amano, Y. Hashimoto, F. Soga, Y. Sato, Nucl. Instr. and Meth. B 227 (2005) 431]. In the present work, ab initio calculations have been carried out in the first Born approximation by using an accurate molecular wave function for describing the initial bound state of the target. The calculated cross sections exhibit good agreement with the present experimental measurements and compare relatively well to the existing semi-empirical results over the entire angular and energy ranges investigated here. Free from any adjustable parameter, the proposed theoretical approach describes in detail the complete kinematics of the water molecule ionization process by highly energetic carbon ions, and could therefore be easily used for modelling the heavy charged-particle transport in the biological matter.

  17. Exposure of PC12 cells to NGF/ethanol results in accelerated differentiation and altered gene expression

    Energy Technology Data Exchange (ETDEWEB)

    White, K.R.; Wooten, M.W. (Auburn Univ., AL (United States))

    1991-03-11

    The role of alcohols in affecting neuromorphogenesis was investigated in the pheochromocytoma cell line, PC12. The effect of ethanol at physiological concentrations in this system leads to accelerated neurite extension in the presence of suboptimal concentrations of NGF. Accelerated morphological differentiation was dependent upon the side chain length of the alcohol and not inhibited by pyrazole. Ethanol/NGF induced neurite extension can be blocked with 50nM of K252a, but not sphingozine, H7, H89, genistein or okadaic acid. Changes in the expression of 17 NGF-induced and/or neuronal transcripts were examined in relationship to time of NGF/ethanol exposure; dose of NGF/ethanol; and side-chain length of NFG/alcohol. The authors studies indicate that ethanol potentiates the effects of NFG and subsequent neurogenesis through both protein kinase C and cAMP-independent pathways. In addition, these data show that ethanol is capable of altering gene expression in a specific manner.

  18. Toxicity and Growth Assessments of Three Thermophilic Benthic Dinoflagellates (Ostreopsis cf. ovata, Prorocentrum lima and Coolia monotis) Developing in the Southern Mediterranean Basin

    Science.gov (United States)

    Ben-Gharbia, Hela; Yahia, Ons Kéfi-Daly; Amzil, Zouher; Chomérat, Nicolas; Abadie, Eric; Masseret, Estelle; Sibat, Manoella; Zmerli Triki, Habiba; Nouri, Habiba; Laabir, Mohamed

    2016-01-01

    Harmful benthic dinoflagellates, usually developing in tropical areas, are expanding to temperate ecosystems facing water warming. Reports on harmful benthic species are particularly scarce in the Southern Mediterranean Sea. For the first time, three thermophilic benthic dinoflagellates (Ostreopsis cf. ovata, Prorocentrum lima and Coolia monotis) were isolated from Bizerte Bay (Tunisia, Mediterranean) and monoclonal cultures established. The ribotyping confirmed the morphological identification of the three species. Maximum growth rates were 0.59 ± 0.08 d−1 for O. cf. ovata, 0.35 ± 0.01 d−1 for C. monotis and 0.33 ± 0.04 d−1 for P. lima. Toxin analyses revealed the presence of ovatoxin-a and ovatoxin-b in O. cf. ovata cells. Okadaic acid and dinophysistoxin-1 were detected in P. lima cultures. For C. monotis, a chromatographic peak at 5.6 min with a mass m/z = 1061.768 was observed, but did not correspond to a mono-sulfated analogue of the yessotoxin. A comparison of the toxicity and growth characteristics of these dinoflagellates, distributed worldwide, is proposed. PMID:27754462

  19. Numerical Investigation of Plasma Detachment in Magnetic Nozzle Experiments

    Science.gov (United States)

    Sankaran, Kamesh; Polzin, Kurt A.

    2008-01-01

    At present there exists no generally accepted theoretical model that provides a consistent physical explanation of plasma detachment from an externally-imposed magnetic nozzle. To make progress towards that end, simulation of plasma flow in the magnetic nozzle of an arcjet experiment is performed using a multidimensional numerical simulation tool that includes theoretical models of the various dispersive and dissipative processes present in the plasma. This is an extension of the simulation tool employed in previous work by Sankaran et al. The aim is to compare the computational results with various proposed magnetic nozzle detachment theories to develop an understanding of the physical mechanisms that cause detachment. An applied magnetic field topology is obtained using a magnetostatic field solver (see Fig. I), and this field is superimposed on the time-dependent magnetic field induced in the plasma to provide a self-consistent field description. The applied magnetic field and model geometry match those found in experiments by Kuriki and Okada. This geometry is modeled because there is a substantial amount of experimental data that can be compared to the computational results, allowing for validation of the model. In addition, comparison of the simulation results with the experimentally obtained plasma parameters will provide insight into the mechanisms that lead to plasma detachment, revealing how they scale with different input parameters. Further studies will focus on modeling literature experiments both for the purpose of additional code validation and to extract physical insight regarding the mechanisms driving detachment.

  20. Study of Adsorption and Flocculation Properties of Natural Clays to Remove Prorocentrum lima

    Directory of Open Access Journals (Sweden)

    Maria Carmen Louzao

    2015-09-01

    Full Text Available High accumulations of phytoplankton species that produce toxins are referred to as harmful algal blooms (HABs. HABs represent one of the most important sources of contamination in marine environments, as well as a serious threat to public health, fisheries, aquaculture-based industries, and tourism. Therefore, methods effectively controlling HABs with minimal impact on marine ecology are required. Marine dinoflagellates of the genera Dinophysis and Prorocentrum are representative producers of okadaic acid (OA and dinophysistoxins responsible for the diarrhetic shellfish poisoning (DSP which is a human intoxication caused by the consumption of shellfish that bioaccumulate those toxins. In this work we explore the use of natural clay for removing Prorocentrum lima. We evaluate the adsorption properties of clays in seawater containing the dinoflagellates. The experimental results confirmed the cell removal through the flocculation of algal and mineral particles leading to the formation of aggregates, which rapidly settle and further entrain cells during their descent. Moreover, the microscopy images of the samples enable one to observe the clays in aggregates of two or more cells where the mineral particles were bound to the outer membranes of the dinoflagellates. Therefore, this preliminary data offers promising results to use these clays for the mitigation of HABs.

  1. Determination of the toxic variability of lipophilic biotoxins in marine bivalve and gastropod tissues treated with an industrial canning process.

    Science.gov (United States)

    García, Carlos; Oyaneder-Terrazas, Javiera; Contreras, Cristóbal; Del Campo, Miguel; Torres, Rafael; Contreras, Héctor R

    2016-11-01

    Contamination of shellfish with lipophilic marine biotoxins (LMB), pectenotoxins (PTXs), yessotoxins (YTXs) and okadaic acid (OA) toxin groups in southern Chile is a constant challenge for the development of miticulture considering the high incidence of toxic episodes that tend to occur. This research is focused on using methodologies for assessing the decrease in toxins of natural resources in Chile with high value, without altering the organoleptic properties of the shellfish. The species were processed through steaming (1 min at 121°C) and subsequent canning (5 min at 121°C). Changes in the profiles of toxins and total toxicity levels of LMB in endemic bivalves and gastropods were determined using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The total reduction of toxicity (≈ 15%) was not related to the destruction of the toxin, but rather to the loss of LMB on removing the shells and packing media of canned products (***p < 0.001). Industrial processing of shellfish reduces LMB contents by up to 15% of the total initial contents, concomitant only with the interconversion of PTX-group toxins into PTX-2sa. In soft bottom-dwelling species with toxicities beyond the standard for safe human consumption (≥ 160 μg OA-eq kg(-)(1)), toxicity can be reduced to safe levels through industrial preparation procedures.

  2. Archaeal signal transduction: impact of protein phosphatase deletions on cell size, motility, and energy metabolism in Sulfolobus acidocaldarius.

    Science.gov (United States)

    Reimann, Julia; Esser, Dominik; Orell, Alvaro; Amman, Fabian; Pham, Trong Khoa; Noirel, Josselin; Lindås, Ann-Christin; Bernander, Rolf; Wright, Phillip C; Siebers, Bettina; Albers, Sonja-Verena

    2013-12-01

    In this study, the in vitro and in vivo functions of the only two identified protein phosphatases, Saci-PTP and Saci-PP2A, in the crenarchaeal model organism Sulfolobus acidocaldarius were investigated. Biochemical characterization revealed that Saci-PTP is a dual-specific phosphatase (against pSer/pThr and pTyr), whereas Saci-PP2A exhibited specific pSer/pThr activity and inhibition by okadaic acid. Deletion of saci_pp2a resulted in pronounced alterations in growth, cell shape and cell size, which could be partially complemented. Transcriptome analysis of the three strains (Δsaci_ptp, Δsaci_pp2a and the MW001 parental strain) revealed 155 genes that were differentially expressed in the deletion mutants, and showed significant changes in expression of genes encoding the archaella (archaeal motility structure), components of the respiratory chain and transcriptional regulators. Phosphoproteome studies revealed 801 unique phosphoproteins in total, with an increase in identified phosphopeptides in the deletion mutants. Proteins from most functional categories were affected by phosphorylation, including components of the motility system, the respiratory chain, and regulatory proteins. In the saci_pp2a deletion mutant the up-regulation at the transcript level, as well as the observed phosphorylation pattern, resembled starvation stress responses. Hypermotility was also observed in the saci_pp2a deletion mutant. The results highlight the importance of protein phosphorylation in regulating essential cellular processes in the crenarchaeon S. acidocaldarius.

  3. Effect of the industrial canning on the toxicity of mussels contaminated with diarrhetic shellfish poisoning (DSP) toxins.

    Science.gov (United States)

    Blanco, Juan; Arévalo, Fabiola; Correa, Jorge; Porro, M Corina; Cabado, Ana G; Vieites, Juan M; Moroño, Angeles

    2016-03-15

    The effect of canning in pickled sauce and autoclaving on weight, toxin content, toxin concentration and toxicity of steamed mussels was studied. Weight decreased by 25.5%. Okadaic acid (OA) and DTX2 content of mussel meat decreased by 24.1 and 42.5%, respectively. The estimated toxicity of the mussel remained nearly unchanged (increased by 2.9%). A part of the toxins lost by the mussels was leached to the sauce but the remaining part should have been thermally degraded. DTX2 underwent more degradation than OA and, in both toxins, free forms more than conjugated ones. This process, therefore, cannot be responsible for the large increments of toxicity of processed mussels -relative to the raw ones-sometimes detected by food processing companies. The final product could be monitored in several ways, but analysing the whole can content or the mussel meat once rehydrated seems to be the most equivalents to the raw mussel controls. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. A protein phosphatase methylesterase (PME-1) is one of several novel proteins stably associating with two inactive mutants of protein phosphatase 2A.

    Science.gov (United States)

    Ogris, E; Du, X; Nelson, K C; Mak, E K; Yu, X X; Lane, W S; Pallas, D C

    1999-05-14

    Carboxymethylation of proteins is a highly conserved means of regulation in eukaryotic cells. The protein phosphatase 2A (PP2A) catalytic (C) subunit is reversibly methylated at its carboxyl terminus by specific methyltransferase and methylesterase enzymes which have been purified, but not cloned. Carboxymethylation affects PP2A activity and varies during the cell cycle. Here, we report that substitution of glutamine for either of two putative active site histidines in the PP2A C subunit results in inactivation of PP2A and formation of stable complexes between PP2A and several cellular proteins. One of these cellular proteins, herein named protein phosphatase methylesterase-1 (PME-1), was purified and microsequenced, and its cDNA was cloned. PME-1 is conserved from yeast to human and contains a motif found in lipases having a catalytic triad-activated serine as their active site nucleophile. Bacterially expressed PME-1 demethylated PP2A C subunit in vitro, and okadaic acid, a known inhibitor of the PP2A methylesterase, inhibited this reaction. To our knowledge, PME-1 represents the first mammalian protein methylesterase to be cloned. Several lines of evidence indicate that, although there appears to be a role for C subunit carboxyl-terminal amino acids in PME-1 binding, amino acids other than those at the extreme carboxyl terminus of the C subunit also play an important role in PME-1 binding to a catalytically inactive mutant.

  5. Phosphatase-dependent regulation of epithelial mitogen-activated protein kinase responses to toxin-induced membrane pores.

    Directory of Open Access Journals (Sweden)

    Jorge L Aguilar

    Full Text Available Diverse bacterial species produce pore-forming toxins (PFT that can puncture eukaryotic cell membranes. Host cells respond to sublytic concentrations of PFT through conserved intracellular signaling pathways, including activation of mitogen-activated protein kinases (MAPK, which are critical to cell survival. Here we demonstrate that in respiratory epithelial cells p38 and JNK MAPK were phosphorylated within 30 min of exposure to pneumolysin, the PFT from Streptococcus pneumoniae. This activation was tightly regulated, and dephosphorylation of both MAPK occurred within 60 min following exposure. Pretreatment of epithelial cells with inhibitors of cellular phosphatases, including sodium orthovanadate, calyculin A, and okadaic acid, prolonged and intensified MAPK activation. Specific inhibition of MAPK phosphatase-1 did not affect the kinetics of MAPK activation in PFT-exposed epithelial cells, but siRNA-mediated knockdown of serine/threonine phosphatases PP1 and PP2A were potent inhibitors of MAPK dephosphorylation. These results indicate an important role for PP1 and PP2A in termination of epithelial responses to PFT and only a minor contribution of dual-specificity phosphatases, such as MAPK phosphatase-1, which are the major regulators of MAPK signals in other cell types. Epithelial regulation of MAPK signaling in response to membrane disruption involves distinct pathways and may require different strategies for therapeutic interventions.

  6. Structure of Protein Phosphatase 2A Core Enzyme Bound to Tumor-Inducing Toxins

    Energy Technology Data Exchange (ETDEWEB)

    Xing,Y.; Xu, Y.; Chen, Y.; Jeffrey, P.; Chao, Y.; Lin, Z.; Li, Z.; Strack, S.; Stock, J.; Shi, Y.

    2006-01-01

    The serine/threonine phosphatase protein phosphatase 2A (PP2A) plays an essential role in many aspects of cellular functions and has been shown to be an important tumor suppressor. The core enzyme of PP2A comprises a 65 kDa scaffolding subunit and a 36 kDa catalytic subunit. Here we report the crystal structures of the PP2A core enzyme bound to two of its inhibitors, the tumor-inducing agents okadaic acid and microcystin-LR, at 2.6 and 2.8 {angstrom} resolution, respectively. The catalytic subunit recognizes one end of the elongated scaffolding subunit by interacting with the conserved ridges of HEAT repeats 11-15. Formation of the core enzyme forces the scaffolding subunit to undergo pronounced structural rearrangement. The scaffolding subunit exhibits considerable conformational flexibility, which is proposed to play an essential role in PP2A function. These structures, together with biochemical analyses, reveal significant insights into PP2A function and serve as a framework for deciphering the diverse roles of PP2A in cellular physiology.

  7. A mollusk VDR/PXR/CAR-like (NR1J) nuclear receptor provides insight into ancient detoxification mechanisms.

    Science.gov (United States)

    Cruzeiro, Catarina; Lopes-Marques, Mónica; Ruivo, Raquel; Rodrigues-Oliveira, Nádia; Santos, Miguel M; Rocha, Maria João; Rocha, Eduardo; Castro, L Filipe C

    2016-05-01

    The origin and diversification of the metazoan endocrine systems represents a fundamental research issue in biology. Nuclear receptors are critical components of these systems. A particular group named VDR/PXR/CAR (NR1I/J) is central in the mediation of detoxification responses. While orthologues have been thoroughly characterized in vertebrates, a sparse representation is currently available for invertebrates. Here, we provide the first isolation and characterization of a lophotrochozoan protostome VDR/PXR/CAR nuclear receptor (NR1J), in the estuarine bivalve the peppery furrow shell (Scrobicularia plana). Using a reporter gene assay, we evaluated the xenobiotic receptor plasticity comparing the human PXR with the S. plana NR1Jβ. Our results show that the molluscan receptor responds to a natural toxin (okadaic acid) in a similar fashion to that reported for other invertebrates. In contrast, the pesticide esfenvalerate displayed a unique response, since it down regulated transactivation at higher concentrations, while for triclosan no response was observed. Additionally, we uncovered lineage specific gene duplications and gene loss in the gene group encoding NRs in protostomes with likely impacts on the complexity of detoxification mechanisms across different phyla. Our findings pave the way for the development of multi-specific sensor tools to screen xenobiotic compounds acting via the NR1I/J group.

  8. Mouse pachytene checkpoint 2 (trip13 is required for completing meiotic recombination but not synapsis.

    Directory of Open Access Journals (Sweden)

    Xin Chenglin Li

    2007-08-01

    Full Text Available In mammalian meiosis, homologous chromosome synapsis is coupled with recombination. As in most eukaryotes, mammalian meiocytes have checkpoints that monitor the fidelity of these processes. We report that the mouse ortholog (Trip13 of pachytene checkpoint 2 (PCH2, an essential component of the synapsis checkpoint in Saccharomyces cerevisiae and Caenorhabditis elegans, is required for completion of meiosis in both sexes. TRIP13-deficient mice exhibit spermatocyte death in pachynema and loss of oocytes around birth. The chromosomes of mutant spermatocytes synapse fully, yet retain several markers of recombination intermediates, including RAD51, BLM, and RPA. These chromosomes also exhibited the chiasmata markers MLH1 and MLH3, and okadaic acid treatment of mutant spermatocytes caused progression to metaphase I with bivalent chromosomes. Double mutant analysis demonstrated that the recombination and synapsis genes Spo11, Mei1, Rec8, and Dmc1 are all epistatic to Trip13, suggesting that TRIP13 does not have meiotic checkpoint function in mice. Our data indicate that TRIP13 is required after strand invasion for completing a subset of recombination events, but possibly not those destined to be crossovers. To our knowledge, this is the first model to separate recombination defects from asynapsis in mammalian meiosis, and provides the first evidence that unrepaired DNA damage alone can trigger the pachytene checkpoint response in mice.

  9. Early Genotoxic and Cytotoxic Effects of the Toxic Dinoflagellate Prorocentrum lima in the Mussel Mytilus galloprovincialis

    Science.gov (United States)

    Prego-Faraldo, María Verónica; Valdiglesias, Vanessa; Laffon, Blanca; Mendez, Josefina; Eirin-Lopez, Jose M.

    2016-01-01

    Okadaic acid (OA) and dinophysistoxins (DTXs) are the main toxins responsible for diarrhetic shellfish poisoning (DSP) intoxications during harmful algal blooms (HABs). Although the genotoxic and cytotoxic responses to OA have been evaluated in vitro, the in vivo effects of these toxins have not yet been fully explored. The present work fills this gap by evaluating the in vivo effects of the exposure to the DSP-toxin-producing dinoflagellate Prorocentrum lima during the simulation of an early HAB episode in the mussel Mytilus galloprovincialis. The obtained results revealed that in vivo exposure to this toxic microalgae induced early genotoxicity in hemocytes, as a consequence of oxidative DNA damage. In addition, the DNA damage observed in gill cells seems to be mainly influenced by exposure time and P. lima concentration, similarly to the case of the oxidative damage found in hemocytes exposed in vitro to OA. In both cell types, the absence of DNA damage at low toxin concentrations is consistent with the notion suggesting that this level of toxicity does not disturb the antioxidant balance. Lastly, in vivo exposure to growing P. lima cell densities increased apoptosis but not necrosis, probably due to the presence of a high number of protein apoptosis inhibitors in molluscs. Overall, this work sheds light into the in vivo genotoxic and cytotoxic effects of P. lima. In doing so, it also demonstrates for the first time the potential of the modified (OGG1) comet assay for assessing oxidative DNA damage caused by marine toxins in marine invertebrates. PMID:27231936

  10. Early Genotoxic and Cytotoxic Effects of the Toxic Dinoflagellate Prorocentrum lima in the Mussel Mytilus galloprovincialis

    Directory of Open Access Journals (Sweden)

    María Verónica Prego-Faraldo

    2016-05-01

    Full Text Available Okadaic acid (OA and dinophysistoxins (DTXs are the main toxins responsible for diarrhetic shellfish poisoning (DSP intoxications during harmful algal blooms (HABs. Although the genotoxic and cytotoxic responses to OA have been evaluated in vitro, the in vivo effects of these toxins have not yet been fully explored. The present work fills this gap by evaluating the in vivo effects of the exposure to the DSP-toxin-producing dinoflagellate Prorocentrum lima during the simulation of an early HAB episode in the mussel Mytilus galloprovincialis. The obtained results revealed that in vivo exposure to this toxic microalgae induced early genotoxicity in hemocytes, as a consequence of oxidative DNA damage. In addition, the DNA damage observed in gill cells seems to be mainly influenced by exposure time and P. lima concentration, similarly to the case of the oxidative damage found in hemocytes exposed in vitro to OA. In both cell types, the absence of DNA damage at low toxin concentrations is consistent with the notion suggesting that this level of toxicity does not disturb the antioxidant balance. Lastly, in vivo exposure to growing P. lima cell densities increased apoptosis but not necrosis, probably due to the presence of a high number of protein apoptosis inhibitors in molluscs. Overall, this work sheds light into the in vivo genotoxic and cytotoxic effects of P. lima. In doing so, it also demonstrates for the first time the potential of the modified (OGG1 comet assay for assessing oxidative DNA damage caused by marine toxins in marine invertebrates.

  11. Biochemical and histological alterations of Mytilus galloprovincialis digestive gland

    Directory of Open Access Journals (Sweden)

    R Auriemma

    2004-11-01

    Full Text Available Electrophoretical and histological analysis were performed on Mytilus galloprovincialis digestivegland samples, in order to detect the presence of a previously identified protein ca 30 kDa MW,synthesized during Dinophysis spp. blooms, and assess a possible correlation between the occurrenceof this protein and okadaic acid (OA exposure by ingestion. Mussels were sampled monthly from July2000 to November 2001 in the Gulf of Trieste (upper Adriatic Sea and immediately processed. Parallelsamples were maintained in sea water plastic tanks and fed with marine invertebrate feed mixed withOA and derivatives at different concentration of toxins for each experimental group (25 mg, 50 mg, 100mg. In tank reared mussels fed with OA, degeneration of digestive cells and appearance of 24.6 kDaprotein were observed, while in wild mussels, neither histological alterations nor presence of a 24.6kDa protein, were detected. A correlation between the toxins concentration and time of appearancewas highlighted, to demonstrate this protein is synthesized in response to OA and derivativesexposure. About the identity of 24.6 kDa protein, it could be an enzyme involved in detoxificationreactions, probably Glyoxalase I.

  12. Yessotoxins, a Group of Marine Polyether Toxins: an Overview

    Directory of Open Access Journals (Sweden)

    José J. Fernández

    2008-05-01

    Full Text Available Yessotoxin (YTX is a marine polyether toxin that was first isolated in 1986 from the scallop Patinopecten yessoensis. Subsequently, it was reported that YTX is produced by the dinoflagellates Protoceratium reticulatum, Lingulodinium polyedrum and Gonyaulax spinifera. YTXs have been associated with diarrhetic shellfish poisoning (DSP because they are often simultaneously extracted with DSP toxins, and give positive results when tested in the conventional mouse bioassay for DSP toxins. However, recent evidence suggests that YTXs should be excluded from the DSP toxins group, because unlike okadaic acid (OA and dinophyisistoxin-1 (DTX-1, YTXs do not cause either diarrhea or inhibition of protein phosphatases . In spite of the increasing number of molecular studies focused on the toxicity of YTX, the precise mechanism of action is currently unknown. Since the discovery of YTX, almost forty new analogues isolated from both mussels and dinoflagellates have been characterized by NMR or LC-MS/MS techniques. These studies indicate a wide variability in the profile and the relative abundance of YTXs in both, bivalves and dinoflagellates. This review covers current knowledge on the origin, producer organisms and vectors, chemical structures, metabolism, biosynthetic origin, toxicological properties, potential risks to human health and advances in detection methods of YTXs.

  13. Modulation of the delayed rectifier K+ current in neurons by an angiotensin II type 2 receptor fragment.

    Science.gov (United States)

    Kang, J; Richards, E M; Posner, P; Sumners, C

    1995-01-01

    Angiotensin II (ANG II) stimulates the delayed rectifier K+ current (IK) in neurons cultured from rat hypothalamus and brain stem via AT2 receptors, and this effect involves activation of a Gi protein and protein phosphatase 2A (PP2A). However, there was no evidence that the AT2 receptor involved in this response was the same as the recently cloned AT2 receptor. In the present study, intracellular injection of a 22-amino acid peptide (PEP-22) corresponding to the putative third intracellular loop of the cloned AT2 receptor elicited an increase in IK in cultured neurons that was similar to the effect produced by ANG II. Furthermore, this effect of PEP-22 was abolished by pertussis toxin (200 ng/ml, 24 h) pretreatment and also by superfusion of the PP2A inhibitor okadaic acid (10 nM), suggesting the involvement of Gi protein and PP2A, respectively. Intracellular injection of a random peptide or normal pipette solution did not affect neuronal IK. This is direct evidence to link the cloned AT2 receptor to a defined response elicited by ANG II.

  14. Radiative Generation of Lepton Masses with the $U(1)'$ Gauge Symmetry

    CERN Document Server

    Okada, Hiroshi

    2014-01-01

    We revisit our previous model proposed in Ref. \\cite{Okada:2013iba}, in which lepton masses except the tauon mass are generated at the one-loop level in a TeV scale physics. Although in the previous work, rather large Yukawa couplings constants; i.e., greater than about 3, are required to reproduce the muon mass, we do not need to introduce such a large but ${\\cal O}$(1) couplings. In our model, masses for neutrinos (charged-leptons) are generated by a dimension five effective operator with two isospin triplet (singlet and doublet) scalar fields. Thus, the mass hierarchy between neutrinos and charged-leptons can be naturally described by the difference in the number of vacuum expectation values (VEVs) of the triplet fields which must be much smaller than the VEV of the doublet field due to the constraint from the electroweak rho parameter. Furthermore, the discrepancy in the measured muon anomalous magnetic moment ($g-2$) from the prediction in the standard model are explained by one-loop contributions from v...

  15. Complex regulation of Arabidopsis AGR1/PIN2-mediated root gravitropic response and basipetal auxin transport by cantharidin-sensitive protein phosphatases

    Science.gov (United States)

    Shin, Heungsop; Shin, Hwa-Soo; Guo, Zibiao; Blancaflor, Elison B.; Masson, Patrick H.; Chen, Rujin

    2005-01-01

    Polar auxin transport, mediated by two distinct plasma membrane-localized auxin influx and efflux carrier proteins/complexes, plays an important role in many plant growth and developmental processes including tropic responses to gravity and light, development of lateral roots and patterning in embryogenesis. We have previously shown that the Arabidopsis AGRAVITROPIC 1/PIN2 gene encodes an auxin efflux component regulating root gravitropism and basipetal auxin transport. However, the regulatory mechanism underlying the function of AGR1/PIN2 is largely unknown. Recently, protein phosphorylation and dephosphorylation mediated by protein kinases and phosphatases, respectively, have been implicated in regulating polar auxin transport and root gravitropism. Here, we examined the effects of chemical inhibitors of protein phosphatases on root gravitropism and basipetal auxin transport, as well as the expression pattern of AGR1/PIN2 gene and the localization of AGR1/PIN2 protein. We also examined the effects of inhibitors of vesicle trafficking and protein kinases. Our data suggest that protein phosphatases, sensitive to cantharidin and okadaic acid, are likely involved in regulating AGR1/PIN2-mediated root basipetal auxin transport and gravitropism, as well as auxin response in the root central elongation zone (CEZ). BFA-sensitive vesicle trafficking may be required for the cycling of AGR1/PIN2 between plasma membrane and the BFA compartment, but not for the AGR1/PIN2-mediated root basipetal auxin transport and auxin response in CEZ cells.

  16. Increased recombination frequency showing evidence of loss of interference is associated with abnormal testicular histopathology.

    Science.gov (United States)

    Varmuza, Susannah; Ling, Ling

    2003-04-01

    Nondisjunction leading to aneuploid gametes has been linked genetically to both increases and decreases in recombination frequency on the aneuploid chromosome. In the present study, we present physical evidence of increased frequency of recombination nodules as measured by Mut-S-like homologue-1 (MLH1) foci on pachytene chromosomes from sterile male mice homozygous for a mutation in the protein phosphatase 1cgamma (PP1cgamma) gene. The pattern of elevated recombination frequency in PP1cgamma mutant spermatocytes is consistent with a loss of interference. Previous studies demonstrated: (1) spermiogenesis is impaired starting at step 8 with a severe reduction in elongating and condensed spermatids; (2) spermatids and sperm exhibit elevated rates of DNA fragmentation; and (3) haploid gametes exhibit elevated levels of aneuploidy. Morphometric analysis of developing testes revealed that the first wave of meiosis proceeds at a normal rate in mutant testes, a surprising result given that the PP1 inhibitor okadaic acid has been shown to accelerate progression of spermatocytes from pachytene to the first meiotic division (MI). Evidence of abnormal testicular histopathology is apparent at 3 weeks, before the appearance of haploid gametes, eliminating the possibility that the mutant phenotype is caused by the presence of abnormal spermatids, but coincident with the appearance of the first set of mid to late pachytene spermatocytes. These observations lead us to conclude that the PP1cgamma mutation causes a complex phenotype, including subtle adverse effects on meiosis, possibly mediated by defective signaling between germ cells and Sertoli cells.

  17. A low molecular weight protein tyrosine phosphatase from Synechocystis sp. strain PCC 6803: enzymatic characterization and identification of its potential substrates

    Science.gov (United States)

    Mukhopadhyay, Archana; Kennelly, Peter J.

    2011-01-01

    The predicted protein product of open reading frame slr0328 from Synechocystis sp. PCC 6803, SynPTP, possesses significant amino acid sequence similarity with known low molecular weight protein tyrosine phosphatases (PTPs). To determine the functional properties of this hypothetical protein, open reading frame slr0328 was expressed in Escherichia coli. The purified recombinant protein, SynPTP, displayed its catalytic phosphatase activity towards several tyrosine, but not serine, phosphorylated exogenous protein substrates. The protein phosphatase activity of SynPTP was inhibited by sodium orthovanadate, a known inhibitor of tyrosine phosphatases, but not by okadaic acid, an inhibitor for many serine/threonine phosphatases. Kinetic analysis indicated that the Km and Vmax values for SynPTP towards p-nitrophenyl phosphate are similar to those of other known bacterial low molecular weight PTPs. Mutagenic alteration of the predicted catalytic cysteine of PTP, Cys7, to serine abolished enzyme activity. Using a combination of immunodetection, mass spectrometric analysis and mutagenically altered Cys7SerAsp125Ala-SynPTP, we identified PsaD (photosystem I subunit II), CpcD (phycocyanin rod linker protein) and phycocyanin-α and -β subunits as possible endogenous substrates of SynPTP in this cyanobacterium. These results indicate that SynPTP might be involved in the regulation of photosynthesis in Synechocystis sp. PCC 6803. PMID:21288886

  18. Joint FAO/WHO/IOC activities to provide scientific advice on marine biotoxins (research report).

    Science.gov (United States)

    Toyofuku, Hajime

    2006-12-01

    The Joint FAO/WHO/IOC ad hoc Expert Consultation on Biotoxins in Molluscan Bivalves performed risk assessments for a number of biotoxins present in bivalve molluscs. For performing risk assessments, the Expert Consultation categorized the biotoxins into eight distinct groups based on chemical structure. The Expert Consultation established LOAELs for the azaspiracid (AZA), okadaic acid (OA), saxitoxin (STX), and domoic acid (DA) toxin groups. The derived provisional acute RfDs for the AZA, OA, STX, and DA toxin groups were 0.04 microg/kg bw, 0.33 microg/kg bw, 0.7 microg/kg bw, and 100 microg/kg bw, respectively. For the yessotoxin (YTX) group, a NOAEL was established, based on animal studies. Applying a safety factor of 100, a provisional acute RfD of 50 microg/kg bw was suggested for the YTX group. The Expert Consultation considered that the database for cyclic imines, brevetoxins, and pectenotoxins was insufficient to establish provisional acute RfDs for these three toxin groups.

  19. Operational tsunami warning: A search for the ad hoc source parameters of rapid/normal/slow sources for tsunami forecast.

    Science.gov (United States)

    Reymond, Dominique; Jamelot, Anthony; Hyvernaud, Olivier; Rivera, Luis

    2017-04-01

    Tsunami modeling involves, as the first requirement, a realistic estimation of the initial coseismic displacement field; in the tsunami warning context, this latter is essentially calculated using Okada, 1992 formulae, that depend on the source dimensions, the focal geometry, the focal depth, and the medium rigidity. While the focal geometry and depth are routinely estimated from inversions of the seismic data, the source dimensions and the coseismic slip are the worst unknowns, because they are entirely lying on scaling and similarities laws between seismic moment and aspect ratio of the source. Our approach will use supplementary parameters given by source duration and its slowness parameter to infer abnormal rupture velocity, and consequently an abnormal rigidity modulus and fault length: a better estimation of the couple (µ, L) will lead to a better estimation of the coseimic slip. Numerical models of the tsunamis generated by the known and well identified slow/rapid sources will be compared to the available observations, showing the importance to take the slowness of the source into account during tsunami warning context.

  20. Sodium arsenite induces chromosome endoreduplication and inhibits protein phosphatase activity in human fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Rong-Nan Huang; I-Ching Ho; Ling-Hui Yih [Institute of Biomedical Sciences, Taiwan (China)] [and others

    1995-08-01

    Arsenic, strongly associated with increased risks of human cancers, is a potent clastogen in a variety of mammalian cell systems. The effect of sodium arsenite (a trivalent arsenic compound) on chromatid separation was studied in human skin fibroblasts (HFW). Human fibroblasts were arrested in S phase by the aid of serum starvation and aphidicolin blocking and then these cells were allowed to synchronously progress into G2 phase. Treatment of the G2-enriched HFW cells with sodium arsenite (0-200 {mu}M) resulted in arrest of cells in the G2 phase, interference with mitotic division, inhibition of spindle assembly, and induction of chromosome endoreduplication in their second mitosis. Sodium arsenite treatment also inhibited the activities of serine/threonine protein phosphatases and enhanced phosphorylation levels of a small heat shock protein (HSP27). These results suggest that sodium arsenite may mimic okadaic acid to induce chromosome endoreduplication through its inhibitory effect on protein phosphatase activity. 61 refs., 6 figs., 2 tabs.

  1. Slow motility in hair cells of the frog amphibian papilla: myosin light chain-mediated shape change.

    Science.gov (United States)

    Farahbakhsh, Nasser A; Narins, Peter M

    2008-07-01

    Using video, fluorescence and confocal microscopy, quantitative analysis and modeling, we investigated intracellular processes mediating the calcium/calmodulin (Ca(2+)/CaM)-dependent slow motility in hair cells dissociated from the rostral region of amphibian papilla, one of the two auditory organs in frogs. The time course of shape changes in these hair cells during the period of pretreatment with several specific inhibitors, as well as their response to the calcium ionophore, ionomycin, were recorded and compared. These cells respond to ionomycin with a tri-phasic shape change: an initial phase of iso-volumetric length decrease; a period of concurrent shortening and swelling; and the final phase of increase in both length and volume. We found that both the myosin light chain kinase inhibitor, ML-7, and antagonists of the multifunctional Ca(2+)/CaM-dependent kinases, KN-62 and KN-93, inhibit the iso-volumetric shortening phase of the response to ionomycin. The type 1 protein phosphatase inhibitors, calyculin A and okadaic acid induce minor shortening on their own, but do not significantly alter phase 1 response. However, they appear to counter effects of the inhibitors of Ca(2+)/CaM-dependent kinases. We hypothesize that an active actomyosin-based process mediates the iso-volumetric shortening in the frog rostral amphibian papillar hair cells.

  2. Development of Certified Reference Materials for Diarrhetic Shellfish Poisoning Toxins, Part 1: Calibration Solutions.

    Science.gov (United States)

    Beach, Daniel G; Crain, Sheila; Lewis, Nancy; LeBlanc, Patricia; Hardstaff, William R; Perez, Ruth A; Giddings, Sabrina D; Martinez-Farina, Camilo F; Stefanova, Roumiana; Burton, Ian W; Kilcoyne, Jane; Melanson, Jeremy E; Quilliam, Michael A; McCarron, Pearse

    2016-09-01

    Okadaic acid (OA) and its analogs dinophysistoxins-1 (DTX1) and -2 (DTX2) are lipophilic polyethers produced by marine dinoflagellates. These toxins accumulate in shellfish and cause diarrhetic shellfish poisoning (DSP) in humans. Regulatory testing of shellfish is essential to safeguard public health and for international trade. Certified reference materials (CRMs) play a key role in analytical monitoring programs. This paper presents an overview of the interdisciplinary work that went into the planning, production, and certification of calibration-solution CRMs for OA, DTX1, and DTX2. OA and DTX1 were isolated from large-scale algal cultures and DTX2 from naturally contaminated mussels. Toxins were isolated by a combination of extraction and chromatographic steps with processes adapted to suit the source and concentration of each toxin. New 19-epi-DSP toxin analogs were identified as minor impurities. Once OA, DTX1, and DTX2 were established to be of suitable purity, solutions were prepared and dispensed into flame-sealed glass ampoules. Certification measurements were carried out using quantitative NMR spectroscopy and LC-tandem MS. Traceability of measurements was established through certified external standards of established purity. Uncertainties were assigned following standards and guidelines from the International Organization for Standardization, with components from the measurement, stability, and homogeneity studies being propagated into final combined uncertainties.

  3. Failure to recall.

    Science.gov (United States)

    Laming, Donald

    2009-01-01

    Mathematical analysis shows that if the pattern of rehearsal in free-recall experiments (of necessity, the pattern observed when participants rehearse aloud) be continued without any further interruption by stimuli (as happens during recall), it terminates with the retrieval of the same 1 word over and over again. Such a terminal state is commonly reached before some of the words in the list have been retrieved even once; those words are not recalled. The 1 minute frequently allowed for recall in free-recall experiments is ample time for retrieval to seize up in this way. The author proposes a model that represents the essential features of the pattern of rehearsal; validates that model by reference to the overt rehearsal data from B. B. Murdock, Jr., and J. Metcalfe (1978) and the recall data from B. B. Murdock, Jr., and R. Okada (1970); demonstrates the long-term properties of continued sequences of retrievals and, also, a fundamental relation linking recall to the total time of presentation; and, finally, compares failure to recall in free-recall experiments with forgetting in general.

  4. Cleavage of Tau by calpain in Alzheimer's disease: the quest for the toxic 17 kD fragment.

    Science.gov (United States)

    Garg, Sarika; Timm, Thomas; Mandelkow, Eva-Maria; Mandelkow, Eckhard; Wang, Yipeng

    2011-01-01

    The amyloid cascade hypothesis of Alzheimer's disease (AD) posits that the generation of β-amyloid (Aβ) triggers Tau neurofibrillary pathology. Recently a "17 kD" calpain-induced Tau fragment, comprising residues 45-230 (molecular weight [MW], 18.7 kD), was proposed to mediate Aβ-induced toxicity. Here, we demonstrate that the "17 kD" fragment is actually much smaller, containing residues 125-230 (molecular weight, 10.7 kD). Inducing Tau phosphorylation by okadaic acid or mimicking phosphorylation by Glu mutations at the epitopes of Alzheimer-diagnostic antibodies AT100/AT8/PHF1 could not prevent the generation of this fragment. The fragment can be induced not only by Aβ oligomers, but also by other cell stressors, e.g., thapsigargin (a Ca(2+)-ATPase inhibitor) or glutamate (an excitatory neurotransmitter). However, overexpression of neither Tau(45-230) nor Tau(125-230) fragment is toxic to Chinese hamster ovary (CHO) cells, neuroblastoma cells (N2a) or primary hippocampal neurons. Finally, the calpain-induced fragment can be observed both in Alzheimer's disease brains and in control normal human brains. We conclude that the 17 kD Tau fragment is not a mediator of Aβ-induced toxicity, leaving open the possibility that upstream calpain activation might cause both Tau fragmentation and toxicity.

  5. Relaxing action of adrenergic β2-agonists on guinea-pig skinned tracheal muscle

    Directory of Open Access Journals (Sweden)

    Kayo Nemoto

    1999-01-01

    Full Text Available Although adrenergic β2-agonist-induced smooth muscle relaxation has been attributed to increased intracellular cyclic AMP (cAMP, a relaxation response has been observed at low β2-agonist concentrations that do not cause increased cAMP To elucidate the mechanism of tracheal muscle relaxation induced by low concentrations of β2-agonists, we used a guinea-pig skinned tracheal smooth muscle preparation to examine the effects on the contractile protein system. The isotonic contraction of β-escin-treated skinned tracheal muscle from guinea-pig was measured. When the intracellular Ca2+ concentration was maintained at 1 μmol/L in the presence of guanosine 5′-triphosphate (GTP; 100 μmol/L, neither isoproterenol (10nmol/L nor salbutamol (60 nmol/L affected Ca2+ sensitivity, but a significant decrease in Ca2+ sensitivity was observed in the presence of okadaic acid (1 μmol/L. The decrease in Ca2+ sensitivity was a slow response and was blocked by pretreatment with propranolol (1 μmol/L. Forskolin (1 μmol/L did not affect Ca2+ sensitivity. These results suggest that adrenergic b 2-agonists may activate protein phosphatase through an unknown pathway involving the β2-receptor, which enhances dephosphorylation of the myosin light chain and/or thin filament proteins, resulting in relaxation of the tracheal smooth muscle.

  6. Suggested Involvement of PP1/PP2A Activity and De Novo Gene Expression in Anhydrobiotic Survival in a Tardigrade, Hypsibius dujardini, by Chemical Genetic Approach

    Science.gov (United States)

    Kondo, Koyuki; Kubo, Takeo; Kunieda, Takekazu

    2015-01-01

    Upon desiccation, some tardigrades enter an ametabolic dehydrated state called anhydrobiosis and can survive a desiccated environment in this state. For successful transition to anhydrobiosis, some anhydrobiotic tardigrades require pre-incubation under high humidity conditions, a process called preconditioning, prior to exposure to severe desiccation. Although tardigrades are thought to prepare for transition to anhydrobiosis during preconditioning, the molecular mechanisms governing such processes remain unknown. In this study, we used chemical genetic approaches to elucidate the regulatory mechanisms of anhydrobiosis in the anhydrobiotic tardigrade, Hypsibius dujardini. We first demonstrated that inhibition of transcription or translation drastically impaired anhydrobiotic survival, suggesting that de novo gene expression is required for successful transition to anhydrobiosis in this tardigrade. We then screened 81 chemicals and identified 5 chemicals that significantly impaired anhydrobiotic survival after severe desiccation, in contrast to little or no effect on survival after high humidity exposure only. In particular, cantharidic acid, a selective inhibitor of protein phosphatase (PP) 1 and PP2A, exhibited the most profound inhibitory effects. Another PP1/PP2A inhibitor, okadaic acid, also significantly and specifically impaired anhydrobiotic survival, suggesting that PP1/PP2A activity plays an important role for anhydrobiosis in this species. This is, to our knowledge, the first report of the required activities of signaling molecules for desiccation tolerance in tardigrades. The identified inhibitory chemicals could provide novel clues to elucidate the regulatory mechanisms underlying anhydrobiosis in tardigrades. PMID:26690982

  7. Apoptosis in barley aleurone during germination and its inhibition by abscisic acid.

    Science.gov (United States)

    Wang, M; Oppedijk, B J; Lu, X; Van Duijn, B; Schilperoort, R A

    1996-12-01

    During germination of barley grains, DNA fragmentation was observed in the aleurone. The appearance of DNA fragmentation in the aleurone layer, observed by TUNEL staining in aleurone sections, started near the embryo and extended to the aleurone cells far from the embryo in a time dependent manner. The same spatial temporal activities of hydrolytic enzymes such as alpha-amylase were observed in aleurone. DNA fragmentation could also be seen in vitro under osmotic stress, in isolated aleurone. During aleurone protoplast isolation, a very enhanced and strong DNA fragmentation occurred which was not seen in protoplast preparations of tobacco leaves. ABA was found to inhibit DNA fragmentation occurring in barley aleurone under osmotic stress condition and during protoplast isolation, while the plant growth regulator gibberellic acid counteracted the effect of ABA. Addition of auxin or cytokinin had no significant effect on DNA fragmentation in these cells. To study the role of phosphorylation in ABA signal transduction leading to control of DNA fragmentation (apoptosis), the effects of the phosphatase inhibitor okadaic acid and of phenylarisine oxide on apoptosis were studied. We hypothesize that the regulation of DNA fragmentation in aleurone plays a very important role in spatial and temporal control of aleurone activities during germination. The possible signal transduction pathway of ABA leading to the regulation of DNA fragmentation is discussed.

  8. COMPARATIVE NUMERICAL SIMULATION OF THE TOHOKU 2011 TSUNAMI

    Directory of Open Access Journals (Sweden)

    Baranova N.A.

    2015-10-01

    Full Text Available The comparative numerical simulation of generation and propagation of tsunami waves generated by the source of the catastrophic 2011 Tohoku earthquake in Japan was performed based on the Okada model and the dynamic keyboard block model. The initial model is connected with the choice of orientation of longitudinal and transverse ruptures within the source region and the values of displacements along the main fault. A subsequent model is based on the premise that the initial stress distribution along the fault zone affects essentially the character of movements around the earthquake source and takes into account the stress-strain state of keyboard blocks. In the first case of the present study, the earthquake source was designated and constructed based on the parameters of the ten largest aftershocks within a finite time interval, while in the second case the source used included all aftershocks on the first day following the main event. Based on such comparative source simulations and far-field tsunami wave measurements, the results with both models were determined to have close similarities. However, in the near-field zone, the agreement with observable data was not as good. That can be attributed to inaccuracies in the placement of virtual tide gauges relative to real ones, as well as to features of bottom relief near the coast.

  9. Analytic crack solutions for tilt fields around hydraulic fractures

    Energy Technology Data Exchange (ETDEWEB)

    Warpinski, N.R.

    2000-01-05

    The recent development of downhole tiltmeter arrays for monitoring hydraulic fractures has provided new information on fracture growth and geometry. These downhole arrays offer the significant advantages of being close to the fracture (large signal) and being unaffected by the free surface. As with surface tiltmeter data, analysis of these measurements requires the inversion of a crack or dislocation model. To supplement the dislocation models of Davis [1983], Okada [1992] and others, this work has extended several elastic crack solutions to provide tilt calculations. The solutions include constant-pressure 2D, penny-shaped, and 3D-elliptic cracks and a 2D-variable-pressure crack. Equations are developed for an arbitrary inclined fracture in an infinite elastic space. Effects of fracture height, fracture length, fracture dip, fracture azimuth, fracture width and monitoring distance on the tilt distribution are given, as well as comparisons with the dislocation model. The results show that the tilt measurements are very sensitive to the fracture dimensions, but also that it is difficult to separate the competing effects of the various parameters.

  10. Sugar-mediated semidian oscillation of gene expression in the cassava storage root regulates starch synthesis

    Energy Technology Data Exchange (ETDEWEB)

    Jansson, Christer; Baguma, Yona; Sun, Chuanxin; Boren, Mats; Olsson, Helena; Rosenqvist, Sara; Mutisya, Joel; Rubaihayo, Patrick R.; Jansson, Christer

    2008-01-15

    Starch branching enzyme (SBE) activity in the cassava storage root exhibited a diurnal fluctuation, dictated by a transcriptional oscillation of the corresponding SBE genes. The peak of SBE activity coincided with the onset of sucrose accumulation in the storage, and we conclude that the oscillatory mechanism keeps the starch synthetic apparatus in the storage root sink in tune with the flux of sucrose from the photosynthetic source. When storage roots were uncoupled from the source, SBE expression could be effectively induced by exogenous sucrose. Turanose, a sucrose isomer that cannot be metabolized by plants, mimicked the effect of sucrose, demonstrating that downstream metabolism of sucrose was not necessary for signal transmission. Also glucose and glucose-1-P induced SBE expression. Interestingly, induction by sucrose, turanose and glucose but not glucose-1-P sustained an overt semidian (12-h) oscillation in SBE expression and was sensitive to the hexokinase (HXK) inhibitor glucosamine. These results suggest a pivotal regulatory role for HXK during starch synthesis. Abscisic acid (ABA) was another potent inducer of SBE expression. Induction by ABA was similar to that of glucose-1-P in that it bypassed the semidian oscillator. Both the sugar and ABA signaling cascades were disrupted by okadaic acid, a protein phosphatase inhibitor. Based on these findings, we propose a model for sugar signaling in regulation of starch synthesis in the cassava storage root.

  11. The Mechanism of Diarrhetic Shellfish Poisoning Toxin Production in Prorocentrum spp.: Physiological and Molecular Perspectives

    Directory of Open Access Journals (Sweden)

    Thomas Chun-Hung Lee

    2016-09-01

    Full Text Available Diarrhetic shellfish poisoning (DSP is a gastrointestinal disorder caused by the consumption of seafood contaminated with okadaic acid (OA and dinophysistoxins (DTXs. OA and DTXs are potent inhibitors of protein phosphatases 2A, 1B, and 2B, which may promote cancer in the human digestive system. Their expression in dinoflagellates is strongly affected by nutritional and environmental factors. Studies have indicated that the level of these biotoxins is inversely associated with the growth of dinoflagellates at low concentrations of nitrogen or phosphorus, or at extreme temperature. However, the presence of leucine or glycerophosphate enhances both growth and cellular toxin level. Moreover, the presence of ammonia and incubation in continuous darkness do not favor the toxin production. Currently, studies on the mechanism of this biotoxin production are scant. Full genome sequencing of dinoflagellates is challenging because of the massive genomic size; however, current advanced molecular and omics technologies may provide valuable insight into the biotoxin production mechanism and novel research perspectives on microalgae. This review presents a comprehensive analysis on the effects of various nutritional and physical factors on the OA and DTX production in the DSP toxin-producing Prorocentrum spp. Moreover, the applications of the current molecular technologies in the study on the mechanism of DSP toxin production are discussed.

  12. The Computation of Global Viscoelastic Co- and Post-seismic Displacement in a Realistic Earth Model by Straightforward Numerical Inverse Laplace Integration

    Science.gov (United States)

    Tang, H.; Sun, W.

    2016-12-01

    The theoretical computation of dislocation theory in a given earth model is necessary in the explanation of observations of the co- and post-seismic deformation of earthquakes. For this purpose, computation theories based on layered or pure half space [Okada, 1985; Okubo, 1992; Wang et al., 2006] and on spherically symmetric earth [Piersanti et al., 1995; Pollitz, 1997; Sabadini & Vermeersen, 1997; Wang, 1999] have been proposed. It is indicated that the compressibility, curvature and the continuous variation of the radial structure of Earth should be simultaneously taken into account for modern high precision displacement-based observations like GPS. Therefore, Tanaka et al. [2006; 2007] computed global displacement and gravity variation by combining the reciprocity theorem (RPT) [Okubo, 1993] and numerical inverse Laplace integration (NIL) instead of the normal mode method [Peltier, 1974]. Without using RPT, we follow the straightforward numerical integration of co-seismic deformation given by Sun et al. [1996] to present a straightforward numerical inverse Laplace integration method (SNIL). This method is used to compute the co- and post-seismic displacement of point dislocations buried in a spherically symmetric, self-gravitating viscoelastic and multilayered earth model and is easy to extended to the application of geoid and gravity. Comparing with pre-existing method, this method is relatively more straightforward and time-saving, mainly because we sum associated Legendre polynomials and dislocation love numbers before using Riemann-Merlin formula to implement SNIL.

  13. A novel sensitive cell-based Love Wave biosensor for marine toxin detection.

    Science.gov (United States)

    Zhang, Xi; Fang, Jiaru; Zou, Ling; Zou, Yingchang; Lang, Lang; Gao, Fan; Hu, Ning; Wang, Ping

    2016-03-15

    A novel HepG2 cell-based biosensor using Love Wave sensor was developed to implement the real-time and sensitive detection of a diarrheic shellfish poisoning (DSP) toxin, Okadaic acid (OA). Detachable Love Wave sensor unit and miniaturized 8-channel recording instrument were designed for the convenient experimental preparation and sensor response signal measurement. The Love Wave sensor, whose synchronous frequency is around 160 MHz, was fabricated with ST-cut quartz substrate. To establish a cell-based biosensor, HepG2 cells as sensing elements were cultured onto the Love Wave sensor surface, and the cell attachment process was recorded by this biosensor. Results showed this sensor could monitor the cell attachment process in real time and response signals were related to the initial cell seeding densities. Furthermore, cell-based Love Wave sensor was treated with OA toxin. This biosensor presented a good performance to various OA concentrations, with a wide linear detection range (10-100 μg/L). Based on the ultrasensitive acoustic wave platform, this cell-based biosensor will be a promising tool for real-time and convenient OA screening.

  14. Invoking Emotions in a Dialog System based on Word-Impressions

    Science.gov (United States)

    Mera, Kazuya; Ichimura, Takumi; Aizawa, Teruaki; Yamashita, Toshiyuki

    There have been some studies about spoken natural language dialog,and most of them have successfully been developed within the speci ed task domains. However,current human-computer interfaces only get the data to process their programs.If the dialog processing has emotion comprehensive faculties, it should lead us to more human-like performance.In this paper,we present a method for constructing an emotion-handling dialog system in order to facilitate more confortable interaction with the users. We describe how to calculate emotions from the utterances,focusing on the similarities between the grammar structures and the semantic structures within the case frame.We made emotion generating calculations(EGC)to generate pleasure/displeasure emotion from an event.We also calculate the degree of the pleasure/displeasure from an opposite angle's length of the rectangular parallelepiped consisting of the all the terms in the EGC.EGC uses 8 type calculations for 12 event classi ed type by Okada. Word impressions about like/dislike are used for their calculations.Furthermore,we apply these calculations to the negatives and the noun phrases.To verify the e ectiveness of the proposed method,we tested some conversations using WWW-based health service system for elderly. We applied our method to 80 event in the conversations and calculated emotions almost corresponded to human-generating emotions.

  15. LibHalfSpace: A C++ object-oriented library to study deformation and stress in elastic half-spaces

    Science.gov (United States)

    Ferrari, Claudio; Bonafede, Maurizio; Belardinelli, Maria Elina

    2016-11-01

    The study of deformation processes in elastic half-spaces is widely employed for many purposes (e.g. didactic, scientific investigation of real processes, inversion of geodetic data, etc.). We present a coherent programming interface containing a set of tools designed to make easier and faster the study of processes in an elastic half-space. LibHalfSpace is presented in the form of an object-oriented library. A set of well known and frequently used source models (Mogi source, penny shaped horizontal crack, inflating spheroid, Okada rectangular dislocation, etc.) are implemented to describe the potential usage and the versatility of the library. The common interface given to library tools enables us to switch easily among the effects produced by different deformation sources that can be monitored at the free surface. Furthermore, the library also offers an interface which simplifies the creation of new source models exploiting the features of object-oriented programming (OOP). These source models can be built as distributions of rectangular boundary elements. In order to better explain how new models can be deployed some examples are included in the library.

  16. Simultaneous 1H PFG-NMR and Confocal Microscopy of Monolayer Cell Cultures: Effects of Apoptosis and Necrosis on Water Diffusion and Compartmentalization

    Energy Technology Data Exchange (ETDEWEB)

    Minard, Kevin R.; Holtom, Gary R.; Kathmann, Loel E.; Majors, Paul D.; Thrall, Brian D.; Wind, Robert A.

    2004-09-01

    Apoptosis and necrosis is induced in monolayer cultures of Chinese hamster ovary cells using okadaic acid and hydrogen peroxide (H2O2) respectively, and the effect on water diffusion and compartmentalization is examined using pulsed-field-gradient (PFG) 1H-NMR and simultaneous confocal microscopy. In PFG experiments characterized by a fixed diffusion time (< 4.7 msec) and variable b-values (0-27,000 s/mm2) 1H-NMR data collected with untreated cells exhibits multi-exponential behavior. Analysis using a slow-exchange model reveals two distinct cellular water compartments with different apparent diffusion coefficients (0.56, 0.06 x 10-3 mm2/sec) and volume fractions (0.96, 0.04). During the first 12 hours of either necrosis or apoptosis the amount of water in the smallest compartment increases two-fold prior to significant changes in cell density or plasma membrane integrity. Over the same period water content in the largest compartment decreases by over a factor of two in apoptotic cells, in accordance with observed cell shrinkage, and changes little in necrotic counterparts where only slight swelling is evident. PFG 1H-NMR therefore serves as a sensitive indicator of early cell death in monolayer cultures and can distinguish apoptosis from necrosis. Measurements of restricted diffusion and water exchange are also presented to elucidate compartment origins and justify model assumptions.

  17. [Frontier of mycobacterium research--host vs. mycobacterium].

    Science.gov (United States)

    Okada, Masaji; Shirakawa, Taro

    2005-09-01

    During the past decade, we have observed advance in tuberculosis research including novel vaccines, innate immunity (TLR), SNIP analysis and molecular mechanism of drug resistance. Worldwide genome project enabled the whole genome sequence of host resistant against tuberculosis as well as the whole genome sequence of M. tuberculosis H37Rv. DNA technology has also provided a great impact on the development of novel vaccine against TB. In this symposium, we have invited leading researchers in the field of the frontier study of Mycobacterium research in order to provide general overview of the cutting edge of frontier research. Molecular mechanism of drug resistance of M. tuberculosis has been clarified. On the other hand, molecular mechanism of host-defence (insusceptibility of host) against M. tuberculosis has not yet elucidated. Dr. Taro Shirakawa (Kyoto University) reviewed the susceptibility genes of host in TB infection and presented candidate genes associated with multi-drug resistant tuberculosis. Dr. Naoto Keicho (International Medical Center of Japan) tried to identify host genetic factors involved in susceptibility to pulmonary Mycobacterium avium complex (MAC) infection by candidate gene approach and genome-wide approach. In Japan, Dr. Masaji Okada (National Hospital Organization Kinki-Chuo Chest Medical Center) has been engaged actively in the development of new tuberculosis vaccines (HVJ-liposome/Hsp65 DNA + IL-12 DNA vaccine and recombinant 72f BCG vaccine). He showed basic strategy for construction of new candidate vaccines and also showed significant efficacy on the protection of tuberculosis infection using cynomolgus monkeys, which are very similar to human tuberculosis. Dr. Hatsumi Taniguchi (University of Occupational and Environmental Health) presented that M. tuberculosis mIHF and the neighbor genes went into a dormacy-like state of M. smegmatis in J774 macrophage cells. This study might provide a weapon for elucidating the mechanism of dormacy

  18. Phycotoxins.

    Science.gov (United States)

    Quilliam, M A

    1999-01-01

    sardines, a common food source of sea lions. This is reminiscent of an incident of mass bird mortality in 1992 in the same region. Toxicological studies of domoic acid continue with one investigation on the effect of pH on toxicity in the mouse assay and others examining toxic effects in rats and cynomolgus monkeys. A study on the uptake and depuration of domoic acid in the Dungeness crab was reported. On October 20, 1997, EU (European Union) directive CE97/61 established a regulatory limit of 20 ppm for domoic acid in European shellfish, the same level as in North America. A detailed study on the oral toxicity of DSP toxins in mice was reported. Recent work by several researchers has revealed the genotoxic potential of okadaic acid and other DSP toxins. Previous work had clearly demonstrated the tumor-promoting potential of DSP toxins, but this recent evidence, which shows mutations in the progeny of okadaic acid-treated cells and the formation of DNA-adducts, increases concerns over the hazards associated with DSP-contaminated shellfish. The toxicology of yessotoxin was evaluated by Ogino et al. The toxin showed weak cytotoxicity, but was not orally lethal to mice at 10 mg/kg, and did not cause intestinal fluid accumulation, inhibition of protein phosphatase 2A (PP2A), or hemolytic effects. Similarly, Tubaro et al. saw no evidence for diarrheogenicity of homoyessotoxin isolated from mussels and from the proposed planktonic producer, Lingulodinium polyedrum. All this provides further evidence that yessotoxin should not be classed as a DSP toxin. A number of new toxins have been detected and identified. Two analogues of yessotoxin, homoyessotoxin, and 45-hydroxyhomoyessotoxin were isolated from mussels of the Adriatic Sea and identified by Satake et al. A recent DSP event in Ireland associated with cultured mussels led to the identification of azaspiracid, a unique marine toxin with spiro ring assemblies. (ABSTRACT TRUNCATED)

  19. Integrated bio-magnetostratigraphy of ODP Site 709 (equatorial Indian Ocean).

    Science.gov (United States)

    Villa, Giuliana; Fioroni, Chiara; Florindo, Fabio

    2015-04-01

    Over the last decade, calcareous nannofossil biostratigraphy of the lower Eocene-Oligocene sediments has shown great potential, through identification of several new nannofossil species and bioevents (e.g. Fornaciari et al., 2010; Bown and Dunkley Jones, 2012; Toffanin et al., 2013). These studies formed the basis for higher biostratigraphic resolution leading to definition of a new nannofossil biozonation (Agnini et al., 2014). In this study, we investigate the middle Eocene-lower Oligocene sediments from ODP Hole 709C (ODP Leg 115) by means of calcareous nannofossils and magnetostratigraphy. Ocean Drilling Program (ODP) Site 709 was located in the equatorial Indian Ocean and biostratigraphy has been investigated in the nineties (Okada, 1990; Fornaciari et al., 1990) while paleomagnetic data from the Initial Report provided only a poorly constrained magnetostratigraphic interpretation, thus the cored succession was dated only by means of biostratigraphy. Our goal is to test the reliability in the Indian Ocean of the biohorizons recently identified at Site 711 (Fioroni et al., in press), by means of high resolution sampling, new taxonomic updates, quantitative analyses on calcareous nannofossils allowed to increase the number of useful bioevents and to compare their reliability and synchroneity. The new magnetostratigraphic analyses and integrated stratigraphy allow also to achieve an accurate biochronology of the time interval spanning Chrons C20 (middle Eocene) and C12 (early Oligocene). In addition, this equatorial site represents an opportunity to study the carbonate accumulation history and the large fluctuations of the carbonate compensation depth (CCD) during the Eocene (e.g. Pälike et al., 2012). The investigated interval encompasses the Middle Eocene Climatic Optimum (MECO), and the long cooling trend that leads to the Oligocene glacial state. By means of our new bio-magnetostratigraphic data and paleoecological results we provide further insights on

  20. Effect of complete protein 4.1R deficiency on ion transportproperties of murine erythrocytes

    Energy Technology Data Exchange (ETDEWEB)

    Rivera, Alicia; De Franceschi, Lucia; Peters, Luanne L.; Gascard,Philippe; Mohandas, Narla; Brugnara, Carlo

    2006-06-02

    abnormal dependence onosmolarity, (K0.5=417 +- 42 in 4.1 -/- vs. 460 +- 35 mOsm in controlmice) suggestive of an up-regulated functional state. While the affinityfor internal protons was not altered (K0.5= 489.7 +- 0.7 vs. 537.0 +-0.56 nM in control mice), the Vmax of the H-induced Na/H exchangeactivity was markedly elevated in 4.1-/- erythrocytes (Vmax 91.47+-7.2compared to 46.52+-5.4 mmol/1013 cell x h in control mice). Na/H exchangeactivation by okadaic acid was absent in 4.1-/- erythrocytes. Altogether,these results suggest that erythroid protein 4.1 plays a major role involume regulation and physiologically down-regulates Na/H exchange inmouse erythrocytes. Up-regulation of the Na/H exchange is an importantcontributor to the elevated cell Na content of 4.1 -/- erythrocytes.-7.2compared to 46.52+-5.4 mmol/1013 cell x h in control mice). Na/H exchangeactivation by okadaic acid was absent in 4.1-/- erythrocytes. Altogether,these results suggest that erythroid protein 4.1 plays a major role involume regulation and physiologically down-regulates Na/H exchange inmouse erythrocytes. Up-regulation of the Na/H exchange is an importantcontributor to the elevated cell Na content of 4.1 -/-erythrocytes.

  1. Tamanho de amostra para avaliação de caracteres de cenoura em sistemas de cultivo agroecológico Sample size for evaluation of carrot traits in agroecologic cultivation systems

    Directory of Open Access Journals (Sweden)

    Giovani Olegário da Silva

    2009-06-01

    Full Text Available O correto dimensionamento de experimentos deve ser utilizado para que se possa reduzir o erro experimental e com isso, maximizar a precisão das informações obtidas. O objetivo deste trabalho foi estimar o número mínimo de famílias e de plantas por parcela para avaliação de caracteres de raiz em uma população de cenoura cultivada em sistema agroecológico. Os ensaios foram conduzidos no verão de 2006/2007 em duas propriedades com cultivo agroecológico em Brasília: Associação Mokiti Okada, que segue modelo de Agricultura Natural em Brazlândia-DF e Núcleo Rural Taguatinga, seguindo modelo de Agricultura Orgânica em Taguatinga-DF. Foram avaliadas 100 famílias de meio-irmãos de cenoura dispostas em delineamento de blocos casualizados com duas repetições e parcelas de 1 m². Foram colhidas 20 plantas competitivas por parcela e avaliadas individualmente para os caracteres comprimento de raiz, diâmetro da raiz, massa da raiz, diâmetro do xilema da raiz, relação diâmetro do xilema/diâmetro da raiz, tipo de ponta da raiz, tipo de ombro da raiz, parâmetro a* para os tecidos xilema e floema. Foi realizada análise de variância conjunta e para cada sistema, com informação entre e dentro de parcelas. Foram realizadas ainda análises de representatividade do número mínimo de famílias e de plantas para representar uma população de cenoura. Foi verificado que uma amostra de 18 plantas competitivas/parcela coletadas em ensaios com 2 repetições, bem como de 74 famílias, são suficientes para garantir uma adequada avaliação de famílias meio-irmãos de cenoura para os caracteres estudados.The correct experiment design should be used to reduce the experimental error and, with that, maximize the precision of the information obtained. The objective of this work was to estimate the minimum number of families and of plants per plot for evaluation of root traits in a carrot population cultivated in agroecologic systems. The

  2. COMMON BEAN CULTIVARS BEHAVIOR IN CONVERSION AREAS TO ORGANIC PRODUCTION SYSTEM IN THE BRAZILIAN SAVANNAH COMPORTAMENTO DE CULTIVARES DE FEIJOEIRO EM ÁREAS DE CONVERSÃO PARA O SISTEMA ORGÂNICO DE PRODUÇÃO NO CERRADO

    Directory of Open Access Journals (Sweden)

    Wellington Pereira de Carvalho

    2007-09-01

    Full Text Available

    The objective of this study was to evaluate the performance of common bean (Phaseolus vulgaris cultivars in a low fertility area cultivated for more than two years with Brachiaria brizantha pasture. These conditions are similar to those of farmers who choose to join the organic system without the necessity of passing through the conversion period. A randomized complete block design with four replications was used. The study was conducted as a local evaluation test with cultivars Aporé, BRS Marfim, BRS Vereda, Pérola, BRS Timbó, Xamego, Jalo Precoce, Diamante Negro, BRS Talismã, BRS Valente, and BRS Radiante as treatments. Two experiments were carried out during 2003, one in the dry season under irrigation, and the other in the rainy season, in organic farming system and following principles and technical norms of Mokiti Okada Certifier. Under irrigation, there were no yield differences between cultivars. In the rainy season, the cultivars BRS Radiante, Jalo Precoce, and BRS Valente showed significant higher yields as compared with the remaining cultivars.The angular leaf spot (Phaeoisariopsis griseola was the most severe disease, and the most susceptible cultivar to this attack was Pérola, in the rainy season.

    KEY-WORDS: Phaseolus vulgaris; yield; cultivar evaluation; organic farming.

    Este trabalho teve por objetivo estudar o desempenho de cultivares de feijão (Phaseolus vulgaris em área cultivada há mais de dois anos com pastagem de Brachiaria brizantha, de baixa fertilidade. Esta situação é semelhante a de produtores que optam por iniciar-se no sistema orgânico, sem a necessidade de passar pelo período de conversão. Utilizou-se o

  3. Seleccion de híbridos de especies de papa por resistencia a Phytophthora infestans (Mont de Bary, fertilidad masculina y potencial productivo Hybrid selection of potatoe species for resistance to Phytophthora infestans (Mont de Bary, male fertility and productive potential

    Directory of Open Access Journals (Sweden)

    Ñustez L. Carlos Eduardo

    1990-12-01

    Full Text Available En la Universidad Nacional de Colombia en Mosquera durante los años 1988 y 1989 se realizó una investigación, donde se evaluó bajo condiciones de invernadero la resistencia a P. infestans de las progenies de 51 cruzamientos (F1 y avanzados. que inclu ían en su pedigree especies silvestres,
    primitivas y/o cultivadas de papa. Luego de un primer ciclo de selección los genotipos escogidos se evaluaron en campo por
    resistencia a la enfermedad, fertilidad masculina y potencial productivo (kg/planta. En invernadero se encontró buena resistencia a razas no específicas de P. infestans en las progenies de los cruzamientos simples con phureja, que incluían las especies silvestres polyadenium, stoloniferum, iopetslum, . avilesii y okadae y susceptibilidad en los que
    tenían las silvestres -dodsii, abancayense, embosinum, canasense, gandarillasii, pampasense, marinasense yalandiae. Al final del segundo ciclo de evaluación
    en campo se seleccionaron 27 genotipos: 5 de cruzamientos simples, 9 de cruzamientos triples y 2 de cruzamientos múltiples que incluyen especies silvestres en su pedigree
    (avilesii, brachycarpum, stotontterum, iopetalum, hougasii, eceule y los 11 restantes incluyen genotipos primitivos y/o avanzados. Un excelente potencial productivo se encontró
    en genotipos del cruzamiento interéspecífico avílesíi x phureja, y en genotipos de cruzamientos triples que incluyen las especies hougasii o acaule. La fertilidad masculina
    de los genotipo evaluados osciló desde esterilidad hasta alta fertilidad.An experiment was carriet out in one of the greenhouses of the Natíonal University of Colombia located in Bogotá, between 1988 and 1989. The objetive was to evaluate. the resistance to P. infestans of the progenies of 51 crosses (F1 and advanced that included in their pedigree wild, primitive specias and/or cultivated potatoes. Then after a first cycle of selection the chosen genotypes were evaluated in

  4. Multi Hazard Assessment: The Azores Archipelagos (PT) case

    Science.gov (United States)

    Aifantopoulou, Dorothea; Boni, Giorgio; Cenci, Luca; Kaskara, Maria; Kontoes, Haris; Papoutsis, Ioannis; Paralikidis, Sideris; Psichogyiou, Christina; Solomos, Stavros; Squicciarino, Giuseppe; Tsouni, Alexia; Xerekakis, Themos

    2016-04-01

    ) and earthquake (475 years return period) was used. Topography, lithology, soil moisture and LU/LC were also accounted for. Soil erosion risk was assessed through the empirical model RUSLE (Renard et al. 1991b). Rainfall erosivity, topography and vegetation cover are the main parameters which were used for predicting the proneness to soil loss. Expected, maximum tsunami wave heights were estimated for a specific earthquake scenario at designated forecast points along the coasts. Deformation at the source was calculated by utilizing the Okada code (Okada, 1985). Tsunami waves' generation and propagation is based on the SWAN model (JRC/IPSC modification). To estimate the wave height (forecast points) the Green's Law function was used (JRC Tsunami Analysis Tool). Storm tracks' historical data indicate a return period of 17 /41 years for H1 /H2 hurricane categories respectively. NOAA WAVEWATCH III model hindcast reanalysis was used to estimate the maximum significant wave height (wind and swell) along the coastline during two major storms. The associated storm-surge risk assessment accounted also for the coastline morphology. Seven empirical (independent) indicators were used to express the erosion susceptibility of the coasts. Each indicator is evaluated according to a semi?quantitative score that represents low, medium and high level of erosion risk or impact. The estimation of the coastal erosion hazard was derived through aggregating the indicators in a grid scale.

  5. Complementarity of phosphorylated histones H2AX and H3 quantification in different cell lines for genotoxicity screening.

    Science.gov (United States)

    Khoury, Laure; Zalko, Daniel; Audebert, Marc

    2016-08-01

    The in vitro micronucleus assay is broadly used, but is not per se able to discriminate aneugenic from clastogenic compounds, and cytotoxicity can be a confounding factor. In vitro genotoxicity assays generally rely on cell lines with limited metabolic capabilities. Recently, the use of histone H2AX and H3 phosphorylation markers (γH2AX and p-H3) was proposed to discriminate aneugenic from clastogenic chemicals. The aim of the present study was to develop a new genotoxic screening strategy based on the use of the γH2AX and p-H3 biomarkers in combination with cell lines with distinct biotransformation properties. First, we tested a training set of 20 model chemicals comprised of 10 aneugens, five clastogens and five cytotoxics on three human cell lines (HepG2, LS-174T and ACHN). Our data confirm the robustness of these two biomarkers to discriminate efficiently clastogens, aneugens and misleading cytotoxic chemicals in HepG2 cells. Aneugenic compounds induced either an increase or a decrease in p-H3 depending on their mode of action. Clastogens induced γH2AX, and cytotoxic compounds generated a marked decrease in these two biomarkers. Moreover, the use of different cell lines permits to discriminate direct from bioactivated genotoxins without the need of an exogenous metabolic activation system. Finally, we further evaluated this strategy using a test set of 13 chemicals with controversial genotoxic potential. The resulting data demonstrate that the combined analysis of γH2AX and p-H3 is an efficient strategy. Notably, we demonstrated that three compounds (fisetin, hydroquinone and okadaic acid) display both aneugenic and clastogenic properties.

  6. Distribution, occurrence and biotoxin composition of the main shellfish toxin producing microalgae within European waters: A comparison of methods of analysis.

    Science.gov (United States)

    McNamee, Sara E; Medlin, Linda K; Kegel, Jessica; McCoy, Gary R; Raine, Robin; Barra, Lucia; Ruggiero, Maria Valeria; Kooistra, Wiebe H C F; Montresor, Marina; Hagstrom, Johannes; Blanco, Eva Perez; Graneli, Edna; Rodríguez, Francisco; Escalera, Laura; Reguera, Beatriz; Dittami, Simon; Edvardsen, Bente; Taylor, Joe; Lewis, Jane M; Pazos, Yolanda; Elliott, Christopher T; Campbell, Katrina

    2016-05-01

    Harmful algal blooms (HABs) are a natural global phenomena emerging in severity and extent. Incidents have many economic, ecological and human health impacts. Monitoring and providing early warning of toxic HABs are critical for protecting public health. Current monitoring programmes include measuring the number of toxic phytoplankton cells in the water and biotoxin levels in shellfish tissue. As these efforts are demanding and labour intensive, methods which improve the efficiency are essential. This study compares the utilisation of a multitoxin surface plasmon resonance (multitoxin SPR) biosensor with enzyme-linked immunosorbent assay (ELISA) and analytical methods such as high performance liquid chromatography with fluorescence detection (HPLC-FLD) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) for toxic HAB monitoring efforts in Europe. Seawater samples (n=256) from European waters, collected 2009-2011, were analysed for biotoxins: saxitoxin and analogues, okadaic acid and dinophysistoxins 1/2 (DTX1/DTX2) and domoic acid responsible for paralytic shellfish poisoning (PSP), diarrheic shellfish poisoning (DSP) and amnesic shellfish poisoning (ASP), respectively. Biotoxins were detected mainly in samples from Spain and Ireland. France and Norway appeared to have the lowest number of toxic samples. Both the multitoxin SPR biosensor and the RNA microarray were more sensitive at detecting toxic HABs than standard light microscopy phytoplankton monitoring. Correlations between each of the detection methods were performed with the overall agreement, based on statistical 2×2 comparison tables, between each testing platform ranging between 32% and 74% for all three toxin families illustrating that one individual testing method may not be an ideal solution. An efficient early warning monitoring system for the detection of toxic HABs could therefore be achieved by combining both the multitoxin SPR biosensor and RNA microarray. Copyright © 2016 Elsevier B

  7. Molecular Genetics of Root Thigmoresponsiveness in Arabidopsis thaliana

    Science.gov (United States)

    Masson, Patrick H.

    2002-01-01

    The molecular mechanisms that allow plant roots to use gravity and touch as growth guides are investigated. We are using a molecular genetic strategy in Arabidopsis thaliana to study these processes. When Arabidopsis thaliana seedlings grow on tilted hard-agar surfaces, their roots develop a wavy pattern of growth which appears to derive from a succession of left-handed and right-handed circumnutation-like processes triggered by gravity and touch stimulation (Okada and Shimura, 1990; Rutherford et al., 1998; Rutherford and Masson, 1996). Interestingly, mutations that affect root waving on tilted hard-agar surfaces can be identified and characterized. Some of these mutations affect root gravitropism, while others appear to be responsible for the production of abnormal waves (no waves, compressed or square waves, coils) without affecting gravitropism. The specific objectives of this project were to functionally characterize two genes (WVD2 and WVD6) which are required for root waving on tilted agar surfaces, but not for root gravitropism. Specific objectives included a physiological and cytological analysis of the mutants, and molecular cloning and characterization of the corresponding genes. As summarized in this paper, we have reached these objectives. We have also identified and partially characterized other mutations that affect root skewing on hard-agar surfaces (sku5-1 and ago1), and have completed our work on the root-wave phenotype associated with mutations in genes of the tryptophan biosynthesis pathway (Lynn et al., 1999; Rutherford et al., 1998; Sedbrook et al., 2000, 2002). We briefly describe our progress on the cloning and characterization of WVD6, WVD2 and SKU5, and provide a list of papers (published, or in preparation) that derived from this grant. We also discuss the biological implications of our findings, with special emphasis on the analysis of WVD2.

  8. Plasmid dependence of Pseudomonas sp. strain NK87 enzymes that degrade 6-aminohexanoate-cyclic dimer.

    Science.gov (United States)

    Kanagawa, K; Negoro, S; Takada, N; Okada, H

    1989-06-01

    A bacterial strain, Pseudomonas sp. strain NK87, that can use 6-aminohexanoate-cyclic dimer as the sole source of carbon and nitrogen was newly isolated from wastewater of a factory which produces nylon-6. Two responsible enzymes, 6-aminohexanoate-cyclic-dimer hydrolase (P-EI) and 6-aminohexanoate-dimer hydrolase (P-EII), were found in the NK87 strain, as is the case with Flavobacterium sp. strain KI72, another 6-aminohexanoate-cyclic-dimer-metabolizing bacterium (H. Okada, S. Negoro, H. Kimura, and S. Nakamura, Nature [London] 306:203-206, 1983). The P-EI enzyme is immunologically identical to the 6-aminohexanoate-cyclic-dimer hydrolase of KI72 (F-EI). However, antiserum against the 6-aminohexanoate-dimer hydrolase purified from KI72 (F-EII) did not react with cell extracts of NK87, indicating that the F-EII and P-EII enzymes are immunologically different. Restriction endonuclease analyses show that the NK87 strain harbors at least six plasmids ranging in size from 20 to 80 kilobase pairs (kbp). The P-EI and P-EII genes were cloned in Escherichia coli. Both the P-EI and F-EI probes strongly hybridized with a 23-kbp plasmid in Southern hybridization analyses. The P-EII probe hybridized specifically with an 80-kbp plasmid, but the F-EII probe hybridized with none of the plasmids harbored in NK87. These results indicate that the P-EI gene and P-EII gene are encoded on the 23-kbp and 80-kbp plasmids, respectively.

  9. Surface deformation due to slow slip source considering a non-elastic medium

    Science.gov (United States)

    Voss, N. K.; Malservisi, R.; Dixon, T. H.; Protti, M.

    2016-12-01

    Slow slip events (SSEs) are now recognized as a feature common in many subduction zones. They have been recognized in both the shallow part of subduction interface as well as deeper, beneath the seismogenic zone. While shallow events are difficult to image due to lack of resolution with onshore instrumentation, deep events appear to correlate well with seismic phenomena including tremor and low frequency events. However, uncertainty regarding source properties of the events and their surrounding medium remains high at these depths. Deep slow slip appears to be located between 60 and 25 km depth at many locations worldwide (Schwartz and Rokosky , 2007). This places the events at depths at or near the mantle wedge corner. Serpentinization of the mantle wedge is thought to be one source of fluids commonly attributed as the source of SSEs and tremor (Wada et al., 2008) but also leads to drastic changes in rheology of the down going slab and near by mantle. Traditionally, measured geodetic transients are inverted for slip distributions using a simple elastic "Okada" type models. Often the shape of these transients is attributed to variance in slip rate on the fault. Here we explore the response of the surrounding lithosphere to the transient stress propagation induced by SSE and the effects on observed surface deformation using varying rheologies within a finite element model. Understanding these effects allows a better estimation of the uncertainty in the geodetically derived slip distributions thus is important to consider when evaluating SSEs role in earthquake hazard as well as deciphering the relationship between tremor and slip.

  10. Amsacrine suppresses matrix metalloproteinase-2 (MMP-2)/MMP-9 expression in human leukemia cells.

    Science.gov (United States)

    Liu, Wen-Hsin; Chen, Ying-Jung; Chien, Jen-Hung; Chang, Long-Sen

    2014-05-01

    This study explores the suppression mechanism of amsacrine (4-(9-Acridinylamino)-N-(methanesulfonyl)-m-anisidine hydrochloride) on matrix metalloproteinase-2 (MMP-2) and MMP-9 expression in human leukemia cells. Amsacrine attenuated cell invasion with decreased MMP-2/MMP-9 protein expression and mRNA levels in U937, Jurkat, HL-60, K562, KU812, and MEG-01 cells. Moreover, amsacrine reduced both MMP-2/MMP-9 promoter luciferase activity and MMP-2/MMP-9 mRNA stability in leukemia cells. Studies on amsacrine-treated U937 cells revealed that amsacrine-elicited ROS generation induced JNK and p38 MAPK activation but reduced the phospho-ERK level. Amsacrine-induced ERK inactivation and p38 MAPK/JNK activation were demonstrated to suppress MMP-2/MMP-9 promoter luciferase activity and promote MMP-2/MMP-9 mRNA decay, respectively. p38 MAPK/JNK activation led to up-regulation of protein phosphatase 2A catalytic subunit α (PP2Acα) in amsacrine-treated U937 cells. Okadaic acid (PP2A inhibitor) treatment increased MMP-2/MMP-9 mRNA stability in amsacrine-treated cells, whereas PP2Acα over-expression increased MMP-2/MMP-9 mRNA decay. Amsacrine-induced MMP-2/MMP-9 down-regulation was also related to PP2Acα up-regulation on Jurkat, HL-60, K562, KU812, and MEG-01 cells. Collectively, our data indicate that amsacrine induces MMP-2/MMP-9 down-regulation via simultaneous suppression of genetic transcription and mRNA stability in human leukemia cells.

  11. Lipid rafts regulate PCB153-induced disruption of occludin and brain endothelial barrier function through protein phosphatase 2A and matrix metalloproteinase-2.

    Science.gov (United States)

    Eum, Sung Yong; Jaraki, Dima; András, Ibolya E; Toborek, Michal

    2015-09-15

    Occludin is an essential integral transmembrane protein regulating tight junction (TJ) integrity in brain endothelial cells. Phosphorylation of occludin is associated with its localization to TJ sites and incorporation into intact TJ assembly. The present study is focused on the role of lipid rafts in polychlorinated biphenyl (PCB)-induced disruption of occludin and endothelial barrier function. Exposure of human brain endothelial cells to 2,2',4,4',5,5'-hexachlorobiphenyl (PCB153) induced dephosphorylation of threonine residues of occludin and displacement of occludin from detergent-resistant membrane (DRM)/lipid raft fractions within 1h. Moreover, lipid rafts modulated the reduction of occludin level through activation of matrix metalloproteinase 2 (MMP-2) after 24h PCB153 treatment. Inhibition of protein phosphatase 2A (PP2A) activity by okadaic acid or fostriecin markedly protected against PCB153-induced displacement of occludin and increased permeability of endothelial cells. The implication of lipid rafts and PP2A signaling in these processes was further defined by co-immunoprecipitation of occludin with PP2A and caveolin-1, a marker protein of lipid rafts. Indeed, a significant MMP-2 activity was observed in lipid rafts and was increased by exposure to PCB153. The pretreatment of MMP-2 inhibitors protected against PCB153-induced loss of occludin and disruption of lipid raft structure prevented the increase of endothelial permeability. Overall, these results indicate that lipid raft-associated processes, such as PP2A and MMP-2 activation, participate in PCB153-induced disruption of occludin function in brain endothelial barrier. This study contributes to a better understanding of the mechanisms leading to brain endothelial barrier dysfunction in response to exposure to environmental pollutants, such as ortho-substituted PCBs.

  12. Protein phosphatase 2A regulates central sensitization in the spinal cord of rats following intradermal injection of capsaicin

    Directory of Open Access Journals (Sweden)

    Fang Li

    2006-03-01

    Full Text Available Abstract Background Intradermal injection of capsaicin into the hind paw of rats induces spinal cord central sensititzation, a process in which the responsiveness of central nociceptive neurons is amplified. In central sensitization, many signal transduction pathways composed of several cascades of intracellular enzymes are involved. As the phosphorylation state of neuronal proteins is strictly controlled and balanced by the opposing activities of protein kinases and phosphatases, the involvement of phosphatases in these events needs to be investigated. This study is designed to determine the influence of serine/threonine protein phosphatase type 2A (PP2A on the central nociceptive amplification process, which is induced by intradermal injection of capsaicin in rats. Results In experiment 1, the expression of PP2A protein in rat spinal cord at different time points following capsaicin or vehicle injection was examined using the Western blot method. In experiment 2, an inhibitor of PP2A (okadaic acid, 20 nM or fostriecin, 30 nM was injected into the subarachnoid space of the spinal cord, and the spontaneous exploratory activity of the rats before and after capsaicin injection was recorded with an automated photobeam activity system. The results showed that PP2A protein expression in the spinal cord was significantly upregulated following intradermal injection of capsaicin in rats. Capsaicin injection caused a significant decrease in exploratory activity of the rats. Thirty minutes after the injection, this decrease in activity had partly recovered. Infusion of a phosphatase inhibitor into the spinal cord intrathecal space enhanced the central sensitization induced by capsaicin by making the decrease in movement last longer. Conclusion These findings indicate that PP2A plays an important role in the cellular mechanisms of spinal cord central sensitization induced by intradermal injection of capsaicin in rats, which may have implications in

  13. Crosstalk between the Smad and the Mitogen-Activated Protein Kinase Pathways is Essential for Erythroid Differentiation of Erythroleukemia Cells Induced by TGF-β, Activin, Hydroxyurea and Butyrate.

    Science.gov (United States)

    Akel, Salem; Bertolette, Daniel; Ruscetti, Francis W

    2013-04-22

    The role of crosstalk between the Smad and the MAPK signaling pathways in activin-, transforming growth factor-β (TGF-β)-, hydroxyurea (HU) - and butyrate-dependent erythroid differentiation of K562 leukemic cells was studied. Treatment with all four inducers caused transient phosphorylation of Smad2/3 and MAPK proteins including ERK, p38 and JNK. Use of specific inhibitors of p38, ERK and JNK MAPK proteins, and TGF-β type I receptor indicated that differentiation induced by each of these agents involves activation of Smad2/3 and p38 MAPK, and inhibition of ERK MAPK. Also, treatment of cells with an inhibitor of protein serine/threonine phosphatase, okadaic acid (OA), induced phosphorylation of Smad2/3, and p38 MAPK, coincident with its induction of erythroid differentiation. Specific inhibition of TGF-β type I receptor kinase activity not only abolished TGF-β/activin effects but also prevented Smad2/3 activation and erythroid differentiation induced by OA, HU and butyrate. The TGF-β type I receptor kinase inhibitor blocked OA-induced differentiation but not p38 MAPK phosphorylation demonstrating that signals from both pathways are needed. As previously observed, addition of ERK1/2 MAPK inhibitors upregulated Smad2/3 phosphorylation and enhanced differentiation, but these effects were dependent on signals from the TGF-β type I receptor. These data indicate that activation of both Smad2/3 and p38 MAPK signaling pathways is a prerequisite to induce erythroid differentiation of erythroleukemia cells by activin, TGF-β, HU, OA and butyrate.

  14. Evidence for involvement of cytosolic thioredoxin peroxidase in the excessive resistance of Sf9 Lepidopteran insect cells against radiation-induced apoptosis.

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    Shashank Hambarde

    Full Text Available Lepidopteran insect cells display 50-100 times higher radioresistance compared to human cells, and reportedly have more efficient antioxidant system that can significantly reduce radiation-induced oxidative stress and cell death. However, the antioxidant mechanisms that contribute substantially to this excessive resistance still need to be understood thoroughly. In this study, we investigated the role of thioredoxin peroxidase (TPx in high-dose γ-radiation response of Sf9 cell line derived from Spodoptera frugiperda, the Fall armyworm. We identified a TPx orthologue (Sf-TPx in Spodoptera system, with primarily cytosolic localization. Gamma-irradiation at 500 Gy dose significantly up-regulated Sf-TPx, while higher doses (1000 Gy-2000 Gy had no such effect. G2/M checkpoint induced following 500 Gy was associated with transition of Sf-TPx decamer into enzymatically active dimer. Same effect was observed during G2/M block induced by 5 nM okadaic acid or 10 µM CDK1 (cycline dependent kinase-1 inhibitor roscovitine, thus indicating that radiation-induced Sf-TPx activity is mediated by CDKs. Accumulation of TPx dimer form during G2/M checkpoint might favour higher peroxidase activity facilitating efficient survival at this dose. Confirming this, higher lethal doses (1000 Gy-2000 Gy caused significantly less accumulation of dimer form and induced dose-dependent apoptosis. A ∼50% knock-down of Sf-TPx by siRNA caused remarkable increase in radiation-induced ROS as well as caspase-3 dependent radiation-induced apoptosis, clearly implying TPx role in the radioresistance of Sf9 cells. Quite importantly, our study demonstrates for the first time that thioredoxin peroxidase contributes significantly in the radioresistance of Lepidopteran Sf9 insect cells, especially in their exemplary resistance against radiation-induced apoptosis. This is an important insight into the antioxidant mechanisms existing in this highly stress-resistant model cell system.

  15. Evidence for involvement of cytosolic thioredoxin peroxidase in the excessive resistance of Sf9 Lepidopteran insect cells against radiation-induced apoptosis.

    Science.gov (United States)

    Hambarde, Shashank; Singh, Vijaypal; Chandna, Sudhir

    2013-01-01

    Lepidopteran insect cells display 50-100 times higher radioresistance compared to human cells, and reportedly have more efficient antioxidant system that can significantly reduce radiation-induced oxidative stress and cell death. However, the antioxidant mechanisms that contribute substantially to this excessive resistance still need to be understood thoroughly. In this study, we investigated the role of thioredoxin peroxidase (TPx) in high-dose γ-radiation response of Sf9 cell line derived from Spodoptera frugiperda, the Fall armyworm. We identified a TPx orthologue (Sf-TPx) in Spodoptera system, with primarily cytosolic localization. Gamma-irradiation at 500 Gy dose significantly up-regulated Sf-TPx, while higher doses (1000 Gy-2000 Gy) had no such effect. G2/M checkpoint induced following 500 Gy was associated with transition of Sf-TPx decamer into enzymatically active dimer. Same effect was observed during G2/M block induced by 5 nM okadaic acid or 10 µM CDK1 (cycline dependent kinase-1) inhibitor roscovitine, thus indicating that radiation-induced Sf-TPx activity is mediated by CDKs. Accumulation of TPx dimer form during G2/M checkpoint might favour higher peroxidase activity facilitating efficient survival at this dose. Confirming this, higher lethal doses (1000 Gy-2000 Gy) caused significantly less accumulation of dimer form and induced dose-dependent apoptosis. A ∼50% knock-down of Sf-TPx by siRNA caused remarkable increase in radiation-induced ROS as well as caspase-3 dependent radiation-induced apoptosis, clearly implying TPx role in the radioresistance of Sf9 cells. Quite importantly, our study demonstrates for the first time that thioredoxin peroxidase contributes significantly in the radioresistance of Lepidopteran Sf9 insect cells, especially in their exemplary resistance against radiation-induced apoptosis. This is an important insight into the antioxidant mechanisms existing in this highly stress-resistant model cell system.

  16. A novel tetratricopeptide repeat (TPR containing PP5 serine/threonine protein phosphatase in the malaria parasite, Plasmodium falciparum

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    Adams Brian

    2001-11-01

    Full Text Available Abstract Background The malarial parasite, Plasmodium falciparum (Pf, is responsible for nearly 2 million deaths worldwide. However, the mechanisms of cellular signaling in the parasite remain largely unknown. Recent discovery of a few protein kinases and phosphatases point to a thriving reversible phosphorylation system in the parasite, although their function and regulation need to be determined. Results We provide biochemical and sequence evidence for a protein serine/threonine phosphatase type PP5 in Plasmodium falciparum, and named it PfPP5. The 594-amino acid polypeptide was encoded by a 1785 nucleotide long intronless gene in the parasite. The recombinant protein, expressed in bacteria, was indistinguishable from native PfPP5. Sequencing comparison indicated that the extra-long N-terminus of PfPP5 outside the catalytic core contained four tetratricopeptide repeats (TPRs, compared to three such repeats in other PP5 phosphatases. The PfPP5 N-terminus was required for stimulation of the phosphatase activity by polyunsaturated fatty acids. Co-immunoprecipitation demonstrated an interaction between native PfPP5 and Pf heat shock protein 90 (hsp90. PfPP5 was expressed in all the asexual erythrocytic stages of the parasite, and was moderately sensitive to okadaic acid. Conclusions This is the first example of a TPR-domain protein in the Apicomplexa family of parasites. Since TPR domains play important roles in protein-protein interaction, especially relevant to the regulation of PP5 phosphatases, PfPP5 is destined to have a definitive role in parasitic growth and signaling pathways. This is exemplified by the interaction between PfPP5 and the cognate chaperone hsp90.

  17. Downregulation of lipin-1 induces insulin resistance by increasing intracellular ceramide accumulation in C2C12 myotubes

    Science.gov (United States)

    Huang, Shujuan; Huang, Suling; Wang, Xi; Zhang, Qingli; Liu, Jia; Leng, Ying

    2017-01-01

    Dysregulation of lipid metabolism in skeletal muscle is involved in the development of insulin resistance. Mutations in lipin-1, a key lipid metabolism regulator leads to significant systemic insulin resistance in fld mice. However, the function of lipin-1 on lipid metabolism and insulin sensitivity in skeletal muscle is still unclear. Herein we demonstrated that downregulation of lipin-1 in C2C12 myotubes by siRNA transfection suppressed insulin action, characterized by reduced insulin stimulated Akt phosphorylation and glucose uptake. Correspondingly, decreased lipin-1 expression was observed in palmitate-induced insulin resistance in C2C12 myotubes, suggested that lipin-1 might play a role in the etiology of insulin resistance in skeletal muscle. The insulin resistance induced by lipin-1 downregulation was related to the disturbance of lipid homeostasis. Lipin-1 silencing reduced intracellular DAG and TAG levels, but elevated ceramide accumulation in C2C12 myotubes. Moreover, the impaired insulin stimulated Akt phosphorylation and glucose uptake caused by lipin-1 silencing could be blocked by the pretreatment with SPT inhibitor myriocin, ceramide synthase inhibitor FB1, or PP2A inhibitor okadaic acid, suggested that the increased ceramide accumulation might be responsible for the development of insulin resistance induced by lipin-1 silencing in C2C12 myotubes. Meanwhile, decreased lipin-1 expression also impaired mitochondrial function in C2C12 myotubes. Therefore, our study suggests that lipin-1 plays an important role in lipid metabolism and downregulation of lipin-1 induces insulin resistance by increasing intracellular ceramide accumulation in C2C12 myotubes. These results offer a molecular insight into the role of lipin-1 in the development of insulin resistance in skeletal muscle. PMID:28123341

  18. Ecology of the ciguatera causing dinoflagellates from the Northern Great Barrier Reef: changes in community distribution and coastal eutrophication.

    Science.gov (United States)

    Skinner, Mark P; Lewis, Richard J; Morton, Steve

    2013-12-15

    Ciguatera fish poisoning (CFP) is known to be caused by the ciguatoxins from the dinoflagellate genus Gambierdiscus, however, there is the potential for other toxins such as okadaic acid and dinophysistoxins from the genus Prorocentrum, and palytoxin from the genus Ostreopsis, to contaminate seafood. These genera may also be indicators of ecosystem health and potentially impact on coral reef ecosystems and the role they may play in the succession of coral to macroalgae dominated reefs has not been researched. Sixteen GBR field sites spanning inshore, mid-lagoon and outer lagoon (offshore) regions were studied. Samples were collected from September 2006 to December 2007 and abundance of benthic dinoflagellates on different host macroalgae and concentration of nutrients present in the water column were determined. The maximum abundance of Prorocentrum, Ostreopsis and Gambierdiscus found was 112, 793 and 50 cells per gram wet weight of host macroalgae, respectively. The average level of Dissolved Inorganic Nitrogen (DIN) in the water column across all sites (0.03 mg/L) was found to be more than double the threshold critical value (0.013 mg/L) for healthy coral reefs. Compared to a previous study 1984, there is evidence of a major shift in the distribution and abundance of these dinoflagellates. Inshore reefs have either of Prorocentrum (as at Green Island) or Ostreopsis (as at Magnetic Island) dominating the macroalgal surface niche which was once dominated by Gambierdiscus, whilst at offshore regions Gambierdiscus is still dominant. This succession may be linked to the ongoing eutrophication of the GBR lagoon and have consequences for the sources of toxins for ongoing cases of ciguatera.

  19. G protein-coupled estrogen receptor 1 (GPER1)/GPR30 increases ERK1/2 activity through PDZ motif-dependent and -independent mechanisms.

    Science.gov (United States)

    Gonzalez de Valdivia, Ernesto; Broselid, Stefan; Kahn, Robin; Olde, Björn; Leeb-Lundberg, L M Fredrik

    2017-06-16

    G protein-coupled receptor 30 (GPR30), also called G protein-coupled estrogen receptor 1 (GPER1), is thought to play important roles in breast cancer and cardiometabolic regulation, but many questions remain about ligand activation, effector coupling, and subcellular localization. We showed recently that GPR30 interacts through the C-terminal type I PDZ motif with SAP97 and protein kinase A (PKA)-anchoring protein (AKAP) 5, which anchor the receptor in the plasma membrane and mediate an apparently constitutive decrease in cAMP production independently of Gi/o Here, we show that GPR30 also constitutively increases ERK1/2 activity. Removing the receptor PDZ motif or knocking down specifically AKAP5 inhibited the increase, showing that this increase also requires the PDZ interaction. However, the increase was inhibited by pertussis toxin as well as by wortmannin but not by AG1478, indicating that Gi/o and phosphoinositide 3-kinase (PI3K) mediate the increase independently of epidermal growth factor receptor transactivation. FK506 and okadaic acid also inhibited the increase, implying that a protein phosphatase is involved. The proposed GPR30 agonist G-1 also increased ERK1/2 activity, but this increase was only observed at a level of receptor expression below that required for the constitutive increase. Furthermore, deleting the PDZ motif did not inhibit the G-1-stimulated increase. Based on these results, we propose that GPR30 increases ERK1/2 activity via two Gi/o-mediated mechanisms, a PDZ-dependent, apparently constitutive mechanism and a PDZ-independent G-1-stimulated mechanism. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  20. Thermal Responses of Growth and Toxin Production in Four Prorocentrum Species from the Central Red Sea

    KAUST Repository

    Aynousah, Arwa

    2017-06-01

    Harmful algae studies, in particular toxic dinoflagellates, and their response to global warming in the Red Sea are still limited. This study was aimed to be the first to characterize the identity, thermal responses and toxin production of four Prorocentrum strains isolated from the Central Red Sea, Saudi Arabia. Morphological and molecular phylogenetic analysis identified the strains as P. elegans, P. rhathymum and P. emarginatum. However, the identity of strain P. sp.6 is currently unresolved, albeit sharing close affinity with P. leve. Growth experiments showed that all species could grow at 24-32°C, but only P. sp.6 survived the 34°C treatment. The optimum temperatures (Topt) estimated from the Gaussian model corresponded to 27.17, 29.33, 26.87, and 27.64°C for P. sp.6, P. elegans, P. rhathymum and P. emarginatum, respectively. However, some discrepancy with the Topt derived from the growth performance were observed for P. elegans and P. emarginatum, as thermal responses differed from the typical Gaussian fit. The Prorocentrum species examined showed a sharp decrease after the optimum temperature resulting in very high activation energies for the fall slope, especially for P. elegans and P. emarginatum. The minimum critical temperature limit for growth was not detected within the range of temperatures examined. Subsequently, high performance liquid chromatography coupled with mass spectrometry (HPLC-MS) analysis revealed all species as non okadaic acid (OA, common toxin of the Prorocentrum genus) producers at any temperature treatment. However, other forms of toxin (i.e. fast acting toxins) not examined here could be produced. Therefore, further investigations are required. The results of this study provided significant contribution to our knowledge regarding the presence, thermal response and toxin production of four Prorocentrum species from the Central Red Sea, Saudi Arabia.

  1. A1 demonstrates restricted tissue distribution during embryonic development and functions to protect against cell death.

    Science.gov (United States)

    Carrió, R.; López-Hoyos, M.; Jimeno, J.; Benedict, M. A.; Merino, R.; Benito, A.; Fernández-Luna, J. L.; Núñez, G.; García-Porrero, J. A.; Merino, J.

    1996-01-01

    Members of the bcl-2 gene family are essential regulators of cell survival in a wide range of biological processes. A1, a member of the family, is known to be expressed in certain adult tissues. However, the precise tissue distribution and function of A1 remains poorly understood. We show here that A1 is expressed in multiple tissues during murine embryonic development. In the embryo, A1 was detected first at embryonic day 11.5 in liver, brain, and limbs. At day 13.5 of gestation, A1 expression was observed in the central nervous system, liver, perichondrium, and digital zones of developing limbs in a pattern different from that of bcl-X. In the central nervous system of 15.5-day embryos, A1 was expressed at high levels in the ventricular zone and cortical plate of brain cortex. Significantly, the interdigital zones of limbs and the intermediate region of the developing brain cortex, two sites associated with extensive cell death, were devoid of A1 and bcl-X. The expression of A1 was retained in many adult tissues. To assess the ability of A1 to modulate cell death, stable transfectants expressing different amounts of A1 protein were generated in K562 cells. Expression of A1 was associated with retardation of apoptotic cell death induced by actinomycin D and cycloheximide as well as by okadaic acid. Confocal microscopy showed that the A1 protein was localized to the cytoplasm in a pattern similar to that of Bcl-2. These results demonstrate that the expression of A1 is wider than previously reported in adult tissues. Furthermore, its distribution in multiple tissues of the embryo suggests that A1 plays a role in the regulation of physiological cell death during embryonic development. Images Figure 1 Figure 2 Figure 3 Figure 5 PMID:8952545

  2. Docosahexaenoic acid inhibits vascular endothelial growth factor (VEGF)-induced cell migration via the GPR120/PP2A/ERK1/2/eNOS signaling pathway in human umbilical vein endothelial cells.

    Science.gov (United States)

    Chao, Che-Yi; Lii, Chong-Kuei; Ye, Siou-Yu; Li, Chien-Chun; Lu, Chia-Yang; Lin, Ai-Hsuan; Liu, Kai-Li; Chen, Haw-Wen

    2014-05-07

    Cell migration plays an important role in angiogenesis and wound repair. Vascular endothelial growth factor (VEGF) is an endothelial cell-specific mitogen that is essential for endothelial cell survival, proliferation, and migration. Docosahexaenoic acid (DHA), an n-3 polyunsaturated fatty acid, shows both anti-inflammatory and antioxidant activities in vitro and in vivo. This study investigated the molecular mechanism by which DHA down-regulates VEGF-induced cell migration. HUVECs were used as the study model, and the MTT assay, Western blot, wound-healing assay, and phosphatase activity assay were used to explore the effects of DHA on cell migration. GPR120 is the putative receptor for DHA action. The results showed that DHA, PD98059 (an ERK1/2 inhibitor), and GW9508 (a GPR120 agonist) inhibited VEGF-induced cell migration. In contrast, pretreatment with okadaic acid (OA, a PP2A inhibitor) and S-nitroso-N-acetyl-DL-penicillamine (an NO donor) reversed the inhibition of cell migration by DHA. VEGF-induced cell migration was accompanied by phosphorylation of ERK1/2 and eNOS. Treatment of HUVECs with DHA increased PP2A enzyme activity and decreased VEGF-induced phosphorylation of ERK1/2 and eNOS. However, pretreatment with OA significantly decreased DHA-induced PP2A enzyme activity and reversed the DHA inhibition of VEGF-induced ERK1/2 and eNOS phosphorylation. These results suggest that stimulation of PP2A activity and inhibition of the VEGF-induced ERK1/2/eNOS signaling pathway may be involved in the DHA suppression of VEGF-induced cell migration. Thus, the effect of DHA on angiogenesis and wound repair is at least partly by virtue of its attenuation of cell migration.

  3. Prevalence of HIV and anemia among pregnant women

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    Bankole Henry Oladeinde

    2011-01-01

    Full Text Available Background: Human immunodeficiency virus (HIV prevalence is high among rural dwellers and pregnant women. Aims: This study aims to determine the prevalence of HIV and anemia among pregnant women attending antenatal clinic in rural community of Okada, Edo State, Nigeria. Patients and Methods: Anticoagulated blood and sera samples were obtained from 480 women consisting of 292 pregnant and 188 non-pregnant women. Antibodies to HIV were detected in the sera samples and hemoglobin concentration of the anticoagulated blood specimens were determined using standard techniques. Anemia was defined as hemoglobin concentration <11g/dl for pregnant women and <12g/dl for non-pregnant women. Results: Pregnancy was not a risk factor for acquiring HIV infection (pregnant vs. non-pregnant: 10.2% vs. 13.8%; OR=0.713, 95% CI=0.407, 1.259, P = 0.247. The prevalence of HIV was significantly (P = 0.005 and P = 0.025 higher in the age group 10-20 years and 21 - 30 years among pregnant and non-pregnant women respectively. Pregnancy was a risk factor for acquiring anemia (OR=1.717, 95% CI=1.179, 2.500, P = 0.006. Only the age of pregnant women significantly (P = 0.004 affected the prevalence of anemia inversely. Conclusion: The prevalence of HIV and anemia among pregnant women were 10.2% and 49.3% respectively. Pregnancy was associated with anemia. Interventions by appropriate agencies are advocated to reduce associated sequelae.

  4. Cardiac β2-Adrenergic Receptor Phosphorylation at Ser355/356 Regulates Receptor Internalization and Functional Resensitization.

    Science.gov (United States)

    Fan, Xiaofang; Gu, Xuejiang; Zhao, Ru; Zheng, Qingqing; Li, Lan; Yang, Wenbing; Ding, Lu; Xue, Feng; Fan, Junming; Gong, Yongsheng; Wang, Yongyu

    2016-01-01

    Previous studies have demonstrated that β2-adrenergic receptors (β2ARs) can be phosphorylated by G protein-coupled receptor kinases (GRKs) and protein kinase A (PKA), affecting β2AR internalization and desensitization. However, the exact physiological function of β2ARs in cardiomyocytes is unknown. In this study, we showed that neonatal mouse cardiomyocytes had different contraction and internalization responses to sustained or repeated, transient agonist stimulation. Specifically, short-time stimulation (10 min) with epinephrine or norepinephrine increased the cardiomyocyte contraction rate, reaching a maximum at 5 min, followed by a slow decline. When the agonist was re-added after a 60-min wash-out period, the increase in the cardiomyocyte contraction rate was similar to the initial response. In contrast, when cardiomyocytes were exposed continuously to epinephrine or norepinephrine for 60 min, the second agonist stimulation did not increase the contraction response. These results indicated that continuous β2AR stimulation caused functional desensitization. Phosphorylation of β2ARs at serine (Ser)355/356 GRK phosphorylation sites, but not at Ser345/346 PKA phosphorylation sites increased with continuous epinephrine stimulation for 60 min. Accordingly, β2AR internalization increased. Interestingly, β2AR internalization was blocked by mutations at the GRK phosphorylation sites, but not by mutations at the PKA phosphorylation sites. Furthermore, inhibition of β2AR dephosphorylation by okadaic acid, a phosphatase 2A inhibitor, impaired the recovery of internalized β2ARs and reduced the cardiomyocyte contraction rate in response to epinephrine. Finally, epinephrine treatment induced the physical interaction of β-arrestin with internalized β2ARs in cardiomyocytes. Together, these data revealed the essential role of the Ser355/356 phosphorylation status of β2ARs in regulating receptor internalization and physiological resensitization in neonatal

  5. P-glycoprotein expression in Perna viridis after exposure to Prorocentrum lima, a dinoflagellate producing DSP toxins.

    Science.gov (United States)

    Huang, Lu; Wang, Jie; Chen, Wen-Chang; Li, Hong-Ye; Liu, Jie-Sheng; Tao Jiang; Yang, Wei-Dong

    2014-08-01

    Bivalves naturally exposed to toxic algae have mechanisms to prevent from harmful effects of diarrhetic shellfish poisoning (DSP) toxins. However, quite few studies have examined the mechanisms associated, and the information currently available is still insufficient. Multixenobiotic resistance (MXR) is ubiquitous in aquatic invertebrates and plays an important role in defense against xenobiotics. Here, to explore the roles of P-glycoprotein (P-gp) in the DSP toxins resistance in shellfish, complete cDNA of P-gp gene in the mussel Perna viridis was cloned and analyzed. The accumulation of okadaic acid (OA), a main component of DSP toxins, MXR activity and expression of P-gp in gills of P. viridis were detected after exposure to Prorocentrum lima, a dinoflagellate producing DSP toxins in the presence or absence of P-gp inhibitors PGP-4008, verapamil (VER) and cyclosporin A (CsA). The mussel P. viridis P-gp closely matches MDR/P-gp/ABCB protein from various organisms, having a typical sequence organization as full transporters from the ABCB family. After exposure to P. lima, OA accumulation, MXR activity and P-gp expression significantly increased in gills of P. viridis. The addition of P-gp-specific inhibitors PGP-4008 and VER decreased MXR activity induced by P. lima, but had no effect on the OA accumulation in gills of P. viridis. However, CsA, a broad-spectrum inhibitor of ABC transporter not only decreased MXR activity, but also increased OA accumulation in gills of P. viridis. Together with the ubiquitous presence of other ABC transporters such as MRP/ABCC in bivalves and potential compensatory mechanism in P-gp and MRP-mediated resistance, we speculated that besides P-gp, other ABC transporters, especially MRP might be involved in the resistance mechanisms to DSP toxins.

  6. Accumulation, transformation and breakdown of DSP toxins from the toxic dinoflagellate Dinophysis acuta in blue mussels, Mytilus edulis.

    Science.gov (United States)

    Nielsen, Lasse Tor; Hansen, Per Juel; Krock, Bernd; Vismann, Bent

    2016-07-01

    Okadaic acid (OA), dinophysistoxins (DTX) and pectenotoxins (PTX) produced by the dinoflagellates Dinophysis spp. can accumulate in shellfish and cause diarrhetic shellfish poisoning upon human consumption. Shellfish toxicity is a result of algal abundance and toxicity as well as accumulation and depuration kinetics in mussels. We mass-cultured Dinophysis acuta containing OA, DTX-1b and PTX-2 and fed it to the blue mussel, Mytilus edulis under controlled laboratory conditions for a week to study toxin accumulation and transformation. Contents of OA and DTX-1b in mussels increased linearly with incubation time, and the net toxin accumulation was 66% and 71% for OA and DTX-1b, respectively. Large proportions (≈50%) of both these toxins were transformed to fatty acid esters. Most PTX-2 was transformed to PTX-2 seco-acid and net accumulation was initially high, but decreased progressively throughout the experiment, likely due to esterification and loss of detectability. We also quantified depuration during the subsequent four days and found half-life times of 5-6 days for OA and DTX-1b. Measurements of dissolved toxins revealed that depuration was achieved through excreting rather than metabolizing toxins. This is the first study to construct a full mass balance of DSP toxins during both accumulation and depuration, and we demonstrate rapid toxin accumulation in mussels at realistic in situ levels of Dinophysis. Applying the observed accumulation and depuration kinetics, we model mussel toxicity, and demonstrate that a concentration of only 75 Dinophysis cells l(-1) is enough to make 60 mm long mussels exceed the regulatory threshold for OA equivalents.

  7. Extraction recoveries and stability of diarrhetic shellfish poisoning (DSP) toxins in naturally contaminated samples.

    Science.gov (United States)

    Rodrigues, S M; Vale, P; Botelho, M J; Gomes, S S

    2009-02-01

    During the last few years the occurrence of a high percentage of esters of diarrhetic shellfish poisoning (DSP) toxins has been observed in shellfish from the Portuguese coast. Most of the commercial bivalves contain DSP toxins in ester forms, either acyl derivatives of okadaic acid (OA) or of dinophysistoxin-2 (DTX-2). The stability of these toxins in shellfish tissues and in raw methanol extracts was investigated in two different naturally contaminated species, mussel and carpet shell, over a 4-week period. The results for both species revealed that DSP toxins were more stable in tissue than in raw methanol extracts. Losses of DSP toxins were seen in the first 2 weeks and were more than 30%, but after that a period of stabilization was observed. The decrease was due probably from losses of esters of OA and DTX-2, the free toxins were stable over the period studied. The extraction most commonly used for chemical and biochemical assays relied on methanolic extraction with aqueous 80% methanol. In this work we have tested the extraction solvent on the extractability of DSP toxins from several naturally contaminated species. A single dispersive extraction with methanol, with solvent ratios of 70%, 80%, 90% and 100%, were tested. After alkaline hydrolysis of esterified toxins and clean-up with hexane and dichloromethane, the samples were analysed by liquid chromatography-mass spectrometry (LC-MS). The recovery of DSP toxins increased with increasing percentages of methanol up to 90%. A decrease in recovery with 100% methanol was observed probably due to problems during the liquid-liquid partitioning.

  8. Rapamycin inhibits BAFF-stimulated cell proliferation and survival by suppressing mTOR-mediated PP2A-Erk1/2 signaling pathway in normal and neoplastic B-lymphoid cells.

    Science.gov (United States)

    Zeng, Qingyu; Zhang, Hai; Qin, Jiamin; Xu, Zhigang; Gui, Lin; Liu, Beibei; Liu, Chunxiao; Xu, Chong; Liu, Wen; Zhang, Shuangquan; Huang, Shile; Chen, Long

    2015-12-01

    B-cell activating factor (BAFF) is involved in not only physiology of normal B cells, but also pathophysiology of aggressive B cells related to malignant and autoimmune diseases. Rapamycin, a lipophilic macrolide antibiotic, has recently shown to be effective in the treatment of human lupus erythematosus. However, how rapamycin inhibits BAFF-stimulated B-cell proliferation and survival has not been fully elucidated. Here, we show that rapamycin inhibited human soluble BAFF (hsBAFF)-induced cell proliferation and survival in normal and B-lymphoid (Raji and Daudi) cells by activation of PP2A and inactivation of Erk1/2. Pretreatment with PD98059, down-regulation of Erk1/2, expression of dominant negative MKK1, or overexpression of wild-type PP2A potentiated rapamycin's suppression of hsBAFF-activated Erk1/2 and B-cell proliferation/viability, whereas expression of constitutively active MKK1, inhibition of PP2A by okadaic acid, or expression of dominant negative PP2A attenuated the inhibitory effects of rapamycin. Furthermore, expression of a rapamycin-resistant and kinase-active mTOR (mTOR-T), but not a rapamycin-resistant and kinase-dead mTOR-T (mTOR-TE), conferred resistance to rapamycin's effects on PP2A, Erk1/2 and B-cell proliferation/viability, implying mTOR-dependent mechanism involved. The findings indicate that rapamycin inhibits BAFF-stimulated cell proliferation/survival by targeting mTOR-mediated PP2A-Erk1/2 signaling pathway in normal and neoplastic B-lymphoid cells. Our data highlight that rapamycin may be exploited for preventing excessive BAFF-induced aggressive B-cell malignancies and autoimmune diseases.

  9. Physically-based modelling of the competition between surface uplift and erosion caused by earthquakes and earthquake sequences.

    Science.gov (United States)

    Hovius, Niels; Marc, Odin; Meunier, Patrick

    2016-04-01

    Large earthquakes deform Earth's surface and drive topographic growth in the frontal zones of mountain belts. They also induce widespread mass wasting, reducing relief. Preliminary studies have proposed that above a critical magnitude earthquake would induce more erosion than uplift. Other parameters such as fault geometry or earthquake depth were not considered yet. A new seismologically consistent model of earthquake induced landsliding allow us to explore the importance of parameters such as earthquake depth and landscape steepness. We have compared these eroded volume prediction with co-seismic surface uplift computed with Okada's deformation theory. We found that the earthquake depth and landscape steepness to be the most important parameters compared to the fault geometry (dip and rake). In contrast with previous studies we found that largest earthquakes will always be constructive and that only intermediate size earthquake (Mw ~7) may be destructive. Moreover, with landscapes insufficiently steep or earthquake sources sufficiently deep earthquakes are predicted to be always constructive, whatever their magnitude. We have explored the long term topographic contribution of earthquake sequences, with a Gutenberg Richter distribution or with a repeating, characteristic earthquake magnitude. In these models, the seismogenic layer thickness, that sets the depth range over which the series of earthquakes will distribute, replaces the individual earthquake source depth.We found that in the case of Gutenberg-Richter behavior, relevant for the Himalayan collision for example, the mass balance could remain negative up to Mw~8 for earthquakes with a sub-optimal uplift contribution (e.g., transpressive or gently-dipping earthquakes). Our results indicate that earthquakes have probably a more ambivalent role in topographic building than previously anticipated, and suggest that some fault systems may not induce average topographic growth over their locked zone during a

  10. Sucrose synthase activity and carbohydrates content in relation to phosphorylation status of Vicia faba root meristems during reactivation from sugar depletion.

    Science.gov (United States)

    Polit, Justyna Teresa; Ciereszko, Iwona

    2012-11-01

    Carbohydrate starvation of Vicia faba root meristems leads to readjustment of carbohydrate metabolism and blocks the cell cycle in two principal control points (PCP1/2). The cell cycle reactivation is possible after sucrose provision, although with a delay of about 12h. During this period, the cells are sensitive to 6-dimethylaminopurine (6-DMAP) and okadaic acid (OA), inhibitors of protein kinases and phosphatases, respectively. The aim of the present study was to investigate whether those inhibitors are involved in inhibition of cell cycle revival through interference with the activities of two sucrose-cleaving enzymes: sucrose synthase (SuSy; EC 2.4.1.13) and invertase (INV; EC 3.2.1.26). In sugar-starved cells, the in situ activity of both enzymes decreased significantly. Following supplementation of root meristems with sugar, INV remained inactive, but SuSy activity increased. Despite the lack of INV activity, glucose was present in meristem cells, but its content was low in cells treated with OA. In the latter case, the size of plastids was reduced, they had less starch, and Golgi structures were affected. In sugar-starved cells, SuSy activity was induced more by exogenous sucrose than by glucose. The sucrose-induced activity was strongly inhibited by OA (less by 6-DMAP) at early stages of regeneration, but not at the stages preceding DNA replication or mitotic activities. The results indicate that prolongation of regeneration and a marked decrease in the number of cells resuming proliferation (observed in previous studies) and resulting from the action of inhibitors, are correlated with the process of SuSy activation at the beginning of regeneration from sugar starvation. Copyright © 2012 Elsevier GmbH. All rights reserved.

  11. Structural Basis for the Catalytic Activity of Human Serine/Threonine Protein Phosphatase type 5 (PP5)

    Science.gov (United States)

    Swingle, Mark R.; Ciszak, Ewa M.; Honkanen, Richard E.

    2004-01-01

    Serine/threonine protein phosphatase-5 (PP5) is a member of the PPP-gene family of protein phosphatases that is widely expressed in mammalian tissues and is highly conserved among eukaryotes. PP5 associates with several proteins that affect signal transduction networks, including the glucocorticoid receptor (GR)-heat shock protein-90 (Hsp90)-heterocomplex, the CDC16 and CDC27 subunits of the anaphase-promoting complex, elF2alpha kinase, the A subunit of PP2A, the G12-alpha / G13-alpha subunits of heterotrimeric G proteins and DNA-PK. The catalytic domain of PP5 (PP5c) shares 35-45% sequence identity with the catalytic domains of other PPP-phosphatases, including protein phosphatase-1 (PP1), -2A (PP2A), -2B / calcineurin (PP2B), -4 (PP4), -6 (PP6), and -7 (PP7). Like PP1, PP2A and PP4, PP5 is also sensitive to inhibition by okadaic acid, microcystin, cantharidin, tautomycin, and calyculin A. Here we report the crystal structure of the PP5 catalytic domain (PP5c) at a resolution of 1.6 angstroms. From this structure we propose a mechanism for PP5-mediated hydrolysis of phosphoprotein substrates, which requires the precise positioning of two metal ions within a conserved Asp(sup 271)-M(sub 1):M(sub 2)-W(sup 1)-His(sup 304)-Asp(sup 274) catalytic motif. The structure of PP5c provides a possible structural basis for explaining the exceptional catalytic proficiency of protein phosphatases, which are among the most powerful known catalysts. Resolution of the entire C-terminus revealed a novel subdomain, and the structure of the PP5c should also aid development of type-specific inhibitors.

  12. Update on the diagnosis and management of Behçet’s disease

    Directory of Open Access Journals (Sweden)

    Rokutanda R

    2014-12-01

    Full Text Available Ryo Rokutanda, Mitsumasa Kishimoto, Masato Okada Immuno-Rheumatology Center, St Luke’s International Hospital, Tokyo, Japan Abstract: Behçet’s disease is a multi-organ disorder that is more common in countries around the Silk Road, and manifests as mucosal ulcers and skin lesions, and with ocular involvement. As a systemic disease, it can also involve gastrointestinal organs and the central nervous or cardiovascular systems. Although the etiology of Behçet's disease is not clearly identified, the pathogenesis of the disease is most commonly hypothesized as a profound inflammatory response triggered by an infectious agent in a genetically susceptible host. As there are no single specific manifestations or specific diagnostic tests, various diagnostic criteria have been proposed around the world, and, among them, the International Study Group criteria have been most commonly used. As the clinical expression of Behçet's disease is heterogeneous, the treatment should be individualized based on involved organs, severity of the disease, and patient's background. The choice of therapeutic agents is limited by lack of clinical trials and is based largely on case reports, case series, and several open-label clinical trials. Corticosteroids, colchicine, and traditional immunosuppressive agents, including azathioprine and cyclosporine, have been used for the treatment of Behçet’s disease. Recently, tumor necrosis factor (TNF inhibitors have become available for several rheumatic diseases, and considerable published data suggest that TNF inhibitors represent an important therapeutic advance for patients with severe and resistant disease, as well as for those with contraindications or intolerance to these treatments. Keywords: Behçet’s disease, therapeutic agents, etiology, diagnosis

  13. Development of a new code to solve hydro-mechanical coupling, shear failure and tensile failure due to hydraulic fracturing operations.

    Science.gov (United States)

    María Gómez Castro, Berta; De Simone, Silvia; Carrera, Jesús

    2016-04-01

    Nowadays, there are still some unsolved relevant questions which must be faced if we want to proceed to the hydraulic fracturing in a safe way. How much will the fracture propagate? This is one of the most important questions that have to be solved in order to avoid the formation of pathways leading to aquifer targets and atmospheric release. Will the fracture failure provoke a microseismic event? Probably this is the biggest fear that people have in fracking. The aim of this work (developed as a part of the EU - FracRisk project) is to understand the hydro-mechanical coupling that controls the shear of existing fractures and their propagation during a hydraulic fracturing operation, in order to identify the key parameters that dominate these processes and answer the mentioned questions. This investigation focuses on the development of a new C++ code which simulates hydro-mechanical coupling, shear movement and propagation of a fracture. The framework employed, called Kratos, uses the Finite Element Method and the fractures are represented with an interface element which is zero thickness. This means that both sides of the element lie together in the initial configuration (it seems a 1D element in a 2D domain, and a 2D element in a 3D domain) and separate as the adjacent matrix elements deform. Since we are working in hard, fragile rocks, we can assume an elastic matrix and impose irreversible displacements in fractures when rock failure occurs. The formulation used to simulate shear and tensile failures is based on the analytical solution proposed by Okada, 1992 and it is part of an iterative process. In conclusion, the objective of this work is to employ the new code developed to analyze the main uncertainties related with the hydro-mechanical behavior of fractures derived from the hydraulic fracturing operations.

  14. The implementation of liquid chromatography tandem mass spectrometry for the official control of lipophilic toxins in seafood: single-laboratory validation under four chromatographic conditions.

    Science.gov (United States)

    García-Altares, M; Diogène, J; de la Iglesia, P

    2013-02-01

    We performed a comprehensive study to assess the fit for purpose of four chromatographic conditions for the determination of six groups of marine lipophilic toxins (okadaic acid and dinophysistoxins, pectenotoxins, azaspiracids, yessotoxins, gymnodimine and spirolides) by LC-MS/MS to select the most suitable conditions as stated by the European Union Reference Laboratory for Marine Biotoxins (EURLMB). For every case, the elution gradient has been optimized to achieve a total run-time cycle of 12 min. We performed a single-laboratory validation for the analysis of three relevant matrices for the seafood aquaculture industry (mussels, pacific oysters and clams), and for sea urchins for which no data about lipophilic toxins have been reported before. Moreover, we have compared the method performance under alkaline conditions using two quantification strategies: the external standard calibration (EXS) and the matrix-matched standard calibration (MMS). Alkaline conditions were the only scenario that allowed detection windows with polarity switching in a 3200 QTrap mass spectrometer, thus the analysis of all toxins can be accomplished in a single run, increasing sample throughput. The limits of quantification under alkaline conditions met the validation requirements established by the EURLMB for all toxins and matrices, while the remaining conditions failed in some cases. The accuracy of the method and the matrix effects where generally dependent on the mobile phases and the seafood species. The MMS had a moderate positive impact on method accuracy for crude extracts, but it showed poor trueness for seafood species other than mussels when analyzing hydrolyzed extracts. Alkaline conditions with EXS and recovery correction for OA were selected as the most proper conditions in the context of our laboratory. This comparative study can help other laboratories to choose the best conditions for the implementation of LC-MS/MS according to their own necessities.

  15. Inferring three-dimensional surface displacement field by combining SAR interferometric phase and amplitude information of ascending and descending orbits

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Conventional Interferometric Synthetic Aperture Radar(InSAR) technology can only measure one-dimensional surface displacement(along the radar line-of-sight(LOS) direction).Here we presents a method to infer three-dimensional surface displacement field by combining SAR interferometric phase and amplitude information of ascending and descending orbits.The method is realized in three steps:(1) measuring surface displacements along the LOS directions of both ascending and descending orbits based on interferometric phases;(2) measuring surface displacements along the azimuth directions of both the ascending and descending orbits based on the SAR amplitude data;and(3) estimating the three-dimensional(3D) surface displacement field by combining the above four independent one-dimensional displacements using the method of least squares and Helmert variance component estimation.We apply the method to infer the 3D surface displacement field caused by the 2003 Bam,Iran,earthquake.The results reveal that in the northern part of Bam the ground surface experienced both subsidence and southwestward horizontal movement,while in the southern part uplift and southeastward horizontal movement occurred.The displacement field thus determined matches the location of the fault very well with the maximal displacements reaching 22,40,and 30 cm,respectively in the up,northing and easting directions.Finally,we compare the 3D displacement field with that simulated from the Okada model.The results demonstrate that the method presented here can be used to generate reliable and highly accurate 3D surface displacement fields.

  16. Lipid rafts regulate PCB153-induced disruption of occludin and brain endothelial barrier function through protein phosphatase 2A and matrix metalloproteinase-2

    Science.gov (United States)

    Eum, Sung Yong; Jaraki, Dima; András, Ibolya E.; Toborek, Michal

    2015-01-01

    Occludin is an essential integral transmembrane protein regulating tight junction (TJ) integrity in brain endothelial cells. Phosphorylation of occludin is associated with its localization to TJ sites and incorporation into intact TJ assembly. The present study is focused on the role of lipid rafts in polychlorinated biphenyl (PCB)-induced disruption of occludin and endothelial barrier function. Exposure of human brain endothelial cells to 2,2′,4,4′,5,5′-hexachlorobiphenyl (PCB153) induced dephosphorylation of threonine residues of occludin and displacement of occludin from detergent-resistant membrane (DRM)/lipid raft fractions within 1 h. Moreover, lipid rafts modulated the reduction of occludin level through activation of matrix metalloproteinase 2 (MMP-2) after 24 h h PCB153 treatment. Inhibition of protein phosphatase 2A (PP2A) activity by okadaic acid or fostriecin markedly protected against PCB153-induced displacement of occludin and increased permeability of endothelial cells. The implication of lipid rafts and PP2A signaling in these processes was further defined by co-immunoprecipitation of occludin with PP2A and caveolin-1, a marker protein of lipid rafts. Indeed, a significant MMP-2 activity was observed in lipid rafts and was increased by exposure to PCB153. The pretreatment of MMP-2 inhibitors protected against PCB153-induced loss of occludin and disruption of lipid raft structure prevented the increase of endothelial permeability. Overall, these results indicate that lipid raft-associated processes, such as PP2A and MMP-2 activation, participate in PCB153-induced disruption of occludin function in brain endothelial barrier. This study contributes to a better understanding of the mechanisms leading to brain endothelial barrier dysfunction in response to exposure to environmental pollutants, such as ortho-substituted PCBs. PMID:26080028

  17. GABAA-current rundown of temporal lobe epilepsy is associated with repetitive activation of GABAA “phasic” receptors

    Science.gov (United States)

    Palma, Eleonora; Roseti, Cristina; Maiolino, Francesca; Fucile, Sergio; Martinello, Katiuscia; Mazzuferi, Manuela; Aronica, Eleonora; Manfredi, Mario; Esposito, Vincenzo; Cantore, Gianpaolo; Miledi, Ricardo; Simonato, Michele; Eusebi, Fabrizio

    2007-01-01

    A study was made of the “rundown” of GABAA receptors, microtransplanted to Xenopus oocytes from surgically resected brain tissues of patients afflicted with drug-resistant human mesial temporal lobe epilepsy (mTLE). Cell membranes, isolated from mTLE neocortex specimens, were injected into frog oocytes that rapidly incorporated functional GABAA receptors. Upon repetitive activation with GABA (1 mM), “epileptic” GABAA receptors exhibited a GABAA-current (IGABA) rundown that was significantly enhanced by Zn2+ (≤250 μM), and practically abolished by the high-affinity GABAA receptor inverse agonist SR95531 (gabazine; 2.5–25 μM). Conversely, IGABA generated by “control” GABAA receptors microtransplanted from nonepileptic temporal lobe, lesional TLE, or authoptic disease-free tissues remained stable during repetitive stimulation, even in oocytes treated with Zn2+. We conclude that rundown of mTLE epileptic receptors depends on the presence of “phasic GABAA receptors” that have low sensitivity to antagonism by Zn2+. Additionally, we found that GABAA receptors, microtransplanted from the cerebral cortex of adult rats exhibiting recurrent seizures, caused by pilocarpine-induced status epilepticus, showed greater rundown than control tissue, an event also occurring in patch-clamped rat pyramidal neurons. Rundown of epileptic rat receptors resembled that of human mTLE receptors, being enhanced by Zn2+ (40 μM) and sensitive to the antiepileptic agent levetiracetam, the neurotrophin brain-derived neurotrophic factor, and the phosphatase blocker okadaic acid. Our findings point to the rundown of GABAA receptors as a hallmark of TLE and suggest that modulating tonic and phasic mTLE GABAA receptor activity may represent a useful therapeutic approach to the disease. PMID:18083839

  18. 3-Formylchromone Interacts with Cysteine 38 in p65 Protein and with Cysteine 179 in IκBα Kinase, Leading to Down-regulation of Nuclear Factor-κB (NF-κB)-regulated Gene Products and Sensitization of Tumor Cells*

    Science.gov (United States)

    Yadav, Vivek R.; Prasad, Sahdeo; Gupta, Subash C.; Sung, Bokyung; Phatak, Sharangdhar S.; Zhang, Shuxing; Aggarwal, Bharat B.

    2012-01-01

    3-Formylchromone (3-FC) has been associated with anticancer potential through a mechanism yet to be elucidated. Because of the critical role of NF-κB in tumorigenesis, we investigated the effect of this agent on the NF-κB activation pathway. Whether activated by inflammatory agents (such as TNF-α and endotoxin) or tumor promoters (such as phorbol ester and okadaic acid), 3-FC suppressed NF-κB activation. It also inhibited constitutive NF-κB expressed by most tumor cells. This activity correlated with sequential inhibition of IκBα kinase (IKK) activation, IκBα phosphorylation, IκBα degradation, p65 phosphorylation, p65 nuclear translocation, and reporter gene expression. We found that 3-FC inhibited the direct binding of p65 to DNA, and this binding was reversed by a reducing agent, thus suggesting a role for the cysteine residue. Furthermore, mutation of Cys38 to Ser in p65 abolished this effect of the chromone. This result was confirmed by a docking study. 3-FC also inhibited IKK activation directly, and the reducing agent reversed this inhibition. Furthermore, mutation of Cys179 to Ala in IKK abolished the effect of the chromone. Suppression of NF-κB activation led to inhibition of anti-apoptotic (Bcl-2, Bcl-xL, survivin, and cIAP-1), proliferative (cyclin D1 and COX-2), invasive (MMP-9 and ICAM-1), and angiogenic (VEGF) gene products and sensitization of tumor cells to cytokines. Thus, this study shows that modification of cysteine residues in IKK and p65 by 3-FC leads to inhibition of the NF-κB activation pathway, suppression of anti-apoptotic gene products, and potentiation of apoptosis in tumor cells. PMID:22065587

  19. Phosphatase control of 4E-BP1 phosphorylation state is central for glycolytic regulation of retinal protein synthesis.

    Science.gov (United States)

    Gardner, Thomas W; Abcouwer, Steven F; Losiewicz, Mandy K; Fort, Patrice E

    2015-09-15

    Control of protein synthesis in insulin-responsive tissues has been well characterized, but relatively little is known about how this process is regulated in nervous tissues. The retina exhibits a relatively high protein synthesis rate, coinciding with high basal Akt and metabolic activities, with the majority of retinal ATP being derived from aerobic glycolysis. We examined the dependency of retinal protein synthesis on the Akt-mTOR signaling and glycolysis using ex vivo rat retinas. Akt inhibitors significantly reduced retinal protein synthesis but did not affect glycolytic lactate production. Surprisingly, the glycolytic inhibitor 2-deoxyglucose (2-DG) markedly inhibited Akt1 and Akt3 activities, as well as protein synthesis. The effects of 2-DG, and 2-fluorodeoxyglucose (2-FDG) on retinal protein synthesis correlated with inhibition of lactate production and diminished ATP content, with all these effects reversed by provision of d-mannose. 2-DG treatment was not associated with increased AMPK, eEF2, or eIF2α phosphorylation; instead, it caused rapid dephosphorylation of 4E-BP1. 2-DG reduced total mTOR activity by 25%, but surprisingly, it did not reduce mTORC1 activity, as indicated by unaltered raptor-associated mTOR autophosphorylation and ribosomal protein S6 phosphorylation. Dephosphorylation of 4E-BP1 was largely prevented by inhibition of PP1/PP2A phosphatases with okadaic acid and calyculin A, and inhibition of PPM1 phosphatases with cadmium. Thus, inhibition of retinal glycolysis diminished Akt and protein synthesis coinciding with accelerated dephosphorylation of 4E-BP1 independently of mTORC1. These results demonstrate a novel mechanism regulating protein synthesis in the retina involving an mTORC1-independent and phosphatase-dependent regulation of 4E-BP1.

  20. Gefitinib induces apoptosis in human glioma cells by targeting Bad phosphorylation.

    Science.gov (United States)

    Chang, Cheng-Yi; Shen, Chiung-Chyi; Su, Hong-Lin; Chen, Chun-Jung

    2011-12-01

    Gefitinib, a selective epidermal growth factor receptor tyrosine kinase inhibitor, is under clinical testing and use in cancer patients, including glioma. However, the molecular mechanisms involved in gefitinib-mediated anticancer effects against glioma remain largely uncharacterized. Gefitinib inhibits cell growth and induces apoptosis in human glioma cells. Gefitinib also induces death of H4 cells with characteristics of the intrinsic apoptotic pathway, including Bax mitochondrial translocation, mitochondrial outer membrane permeabilization, cytochrome c cytosolic release, and caspase-9/caspase-3 activation. The importance of Bax in mediating gefitinib-induced apoptosis was confirmed by the attenuation of apoptosis by Bax siRNA and Bax channel blocker. Gefitinib caused Bad dephosphorylation, particularly in serine-112, and increased its binding preference to Bcl-2 and Bcl-xL. The dephosphorylation of Bad in gefitinib-treated cells was accompanied by reduced intracellular cyclic AMP content and protein kinase A (PKA) activity. Adenylyl cyclase activator forskolin attenuated, but PKA inhibitor H89 augmented, gefitinib-induced Bad dephosphorylation, Bax mitochondrial translocation, caspase-9/caspase-3 activation, and viability loss. Intriguingly, a nonselective protein phosphatase inhibitor okadaic acid alleviated gefitinib-induced alterations, except Bad dephosphorylation. In parallel with the higher basal PKA activity, response of U87 cells to gefitinib treatment was delayed and relatively resistant compared with that of H4 and T98G cells. Inactivation of PKA sensitized H4, T98G, and U87 cells to gefitinib cytotoxicity, Bad dephosphorylation in serine-112, and caspase-9/caspase-3 activation. Our findings suggest the involvement of the Bad/Bax signaling pathway in gefitinib-induced glioma apoptosis. Furthermore, the inactivation of PKA was shown to play a role in triggering the proapoptotic function of Bad.

  1. Numerical Investigation of Plasma Flows in Magnetic Nozzles

    Science.gov (United States)

    Sankaran, Kamesh; Polzin, Kurt A.

    2009-01-01

    Magnetic nozzles are used in many laboratory experiments in which plasma flows are to be confined, cooled, accelerated, or directed. At present, however, there is no generally accepted theoretical description that explains the phenomena of plasma expansion in and detachment from an externally-imposed magnetic field. The latter is an especially important problem in the field of plasma propulsion, where the ionized gas must detach from the applied, solenoidal magnetic field to realize thrust production. In this paper we simulate a plasma flowing in the presence of an applied magnetic field using a multidimensional numerical simulation tool that includes theoretical models of the various dispersive and dissipative processes present in the plasma. This is an extension of the simulation tool employed in previous work by Sankaran et al. The new tool employs the same formulation of the governing equation set, but retains the axial and radial components of magnetic field and the azimuthal component of velocity that were neglected. We aim to compare the computational results with the various proposed magnetic nozzle detachment theories to develop an understanding of the physical mechanisms that cause detachment. An applied magnetic field topology is obtained using a magnetostatic field solver, and this field is superimposed on the time-dependent magnetic field induced in the plasma to provide a self-consistent field description. The applied magnetic field and model geometry match those found in experiments by Kuriki and Okada. 4 A schematic showing the setup used in those experiments is shown. We model this geometry because there is a substantial amount of experimental data that can be compared to our computations, allowing for validation of the model. In addition, comparison of the simulation results with the experimentally obtained plasma parameters will provide insight into the mechanisms that lead to plasma detachment, revealing how they scale with different input

  2. Histone H3 phosphorylation in the rat pineal gland: adrenergic regulation and diurnal variation.

    Science.gov (United States)

    Chik, C L; Arnason, T G; Dukewich, W G; Price, D M; Ranger, A; Ho, A K

    2007-04-01

    In this study, we investigated phosphorylation of Ser10 in histone H3 by norepinephrine (NE) in the rat pineal gland. In whole-animal studies, we demonstrated a marked increase in histone H3 phosphorylation in the rat pineal gland during the first half of the dark period. Exposure to light during this period caused a rapid decline in histone H3 phosphorylation with an estimated t1/2 of less than 15 min, indicating a high level of dephosphorylation activity. Corresponding studies in cultured pineal cells revealed that treatment with NE produced an increase in histone H3 phosphorylation that peaked between 2 and 3 h and declined rapidly by 4 h. The NE-induced histone H3 phosphorylation was blocked by cotreatment with propranolol or KT5720, a protein kinase A inhibitor, but not by prazosin or other kinase inhibitors. Moreover, only treatment with dibutyryl cAMP but not other kinase activators mimicked the effect of NE on histone H3 phosphorylation. The NE-stimulated H3 phosphorylation was markedly increased by cotreatment with a serine/threonine phosphatase inhibitor, tautomycin or okadaic acid, supporting a high level of ongoing histone H3 dephosphorylation activity. Together, our results indicate that histone H3 phosphorylation is a naturally occurring event at night in the rat pineal gland that is driven almost exclusively by a NE-->beta-adrenergic-->cAMP/protein kinase A signaling mechanism. This transient histone H3 phosphorylation probably reflects the nocturnal activation of multiple adrenergic-regulated genes in the rat pineal gland.

  3. A new genus of anthophilous drosophilids, Impatiophila (Diptera, Drosophilidae): morphology, DNA barcoding and molecular phylogeny, with descriptions of thirty-nine new species.

    Science.gov (United States)

    Fu, Zhao; Toda, Masanori J; Li, Nan-Nan; Zhang, Ya-Ping; Gao, Jian-Jun

    2016-06-03

    Breeding habits of essential dependence on flowers for larval food resources have evolved repeatedly in separate lineages of the Drosophilidae. However, flowers of Impatiens L. have never been recognized as hosts for drosophilid flies until recently: two Hirtodrosophila species, H. actinia (Okada) and H. yapingi Gao, were found feeding and breeding on Impatiens flowers. During our recent field surveys in central and southern China, a great number of drosophilid flies morphologically resembling the two species were collected, almost exclusively from flowers of Impatiens (family Balsaminaceae) and the family Gesneriaceae. In the present study, these specimens were identified on the basis of morphological characters and/or partial DNA sequences of the mitochondrial COI (cytochrome c oxidase subunit I gene, used as a barcoding marker). As a result, 39 new species were recognized. We then reconstructed the phylogenetic relationships among most of them, based on concatenated DNA sequences (3047 nucleotide sites) of two mitochondrial (COI and COII, i.e., cytochrome c oxidase subunits I and II, respectively) and three nuclear genes (ATPsyn-alpha, alphaTub84B and Hsc70cb, i.e., ATP synthase alpha, alpha-Tubulin at 84B and Hsc70Cb isoform H, respectively). In the resulting Bayesian and ML (maximum likelihood) trees, three well-supported clades were recognized, with a few species having remained uncertain for their phylogenetic positions. We also conducted a cladistic analysis with data of adult morphological characters to investigate the phylogenetic positions of a few species of which DNA sequence data were not available, and to investigate the classification of species groups with definition of their diagnoses. In consequence, we established a new genus, Impatiophila, for the species visiting flowers of Impatiens and Gesneriaceae, described all the new species, and revised the taxonomy of some known species.

  4. OS EFEITOS DO TREINO DE TIRO COM ZARABATANA NA CAPACIDADE RESPIRATÓRIA DE PESSOAS COM TRISSOMIA 21 APÓS UM ANO DE DESTREINO

    Directory of Open Access Journals (Sweden)

    C. Leitão

    2015-05-01

    Full Text Available Em 2011 estimava-se que houvesse entre 12 a 15 mil crianças com Trissomia 21 (Martinho, 2011. A capacidade respiratória está relacionada com a permuta do ar atmosférico com o ar existente no interior dos pulmões (McArdle, Katch & Katch, 2001, sendo que este processo apresenta-se mais dificultado em sujeitos com Trissomia 21 pois exibem valores de pressão expiratória máxima abaixo dos 50% e de pressão inspiratória máxima abaixo dos 60% previstos para a população sedentária saudável (Castoldi, Périco & Grave, 2012. O treino de tiro com zarabatana tem influência no aumento da pressão expiratória máxima e tem um efeito sobre a função respiratória, semelhante ao treino muscular de músculos expiratório em adultos (Nagasaki, Okada, Kai, & Takahashi, 2010. Segundo (Mariñas & Higuchi, 2010 a zarabatana trata-se de um tubo comprido, através do qual são expelidos pequenos projéteis, através do sopro com objetivo de atingir um alvo. A introdução da atividade de tiro com zarabatana surge de modo a minimizar os problemas respiratórios desta população, porque envolve todo o ciclo respiratório e por ser uma atividade lúdica. Objetivo: Comparar os efeitos do treino de tiro com zarabatana na capacidade respiratória de pessoas com trissomia 21 após um ano de destreino.

  5. Pharmacological manipulation of the akt signaling pathway regulates myxoma virus replication and tropism in human cancer cells.

    Science.gov (United States)

    Werden, Steven J; McFadden, Grant

    2010-04-01

    Viruses have evolved an assortment of mechanisms for regulating the Akt signaling pathway to establish a cellular environment more favorable for viral replication. Myxoma virus (MYXV) is a rabbit-specific poxvirus that encodes many immunomodulatory factors, including an ankyrin repeat-containing host range protein termed M-T5 that functions to regulate tropism of MYXV for rabbit lymphocytes and certain human cancer cells. MYXV permissiveness in these human cancer cells is dependent upon the direct interaction between M-T5 and Akt, which has been shown to induce the kinase activity of Akt. In this study, an array of compounds that selectively manipulate Akt signaling was screened and we show that only a subset of Akt inhibitors significantly decreased the ability of MYXV to replicate in previously permissive human cancer cells. Furthermore, reduced viral replication efficiency was correlated with lower levels of phosphorylated Akt. In contrast, the PP2A-specific phosphatase inhibitor okadaic acid promoted increased Akt kinase activation and rescued MYXV replication in human cancer cells that did not previously support viral replication. Finally, phosphorylation of Akt at residue Thr308 was shown to dictate the physical interaction between Akt and M-T5, which then leads to phosphorylation of Ser473 and permits productive MYXV replication in these human cancer cells. The results of this study further characterize the mechanism by which M-T5 exploits the Akt signaling cascade and affirms this interaction as a major tropism determinant that regulates the replication efficiency of MYXV in human cancer cells.

  6. Pph1 from Myxococcus xanthus is a protein phosphatase involved in vegetative growth and development.

    Science.gov (United States)

    Treuner-Lange, A; Ward, M J; Zusman, D R

    2001-04-01

    Myxococcus xanthus is a Gram-negative bacterium with a complex life cycle that includes vegetative swarming on rich medium and, upon starvation, aggregation to form fruiting bodies containing spores. Both of these behaviours require multiple Ser/Thr protein kinases. In this paper, we report the first Ser/Thr protein phosphatase gene, pph1, from M. xanthus. DNA sequence analysis of pph1 indicates that it encodes a protein of 254 residues (Mr = 28 308) with strong homology to eukaryotic PP2C phosphatases and that it belongs to a new group of bacterial protein phosphatases that are distinct from bacterial PP2C phosphatases such as RsbU, RsbX and SpoIIE. Recombinant His-tagged Pph1 was purified from Escherichia coli and shown to have Mn2+ or Mg2+ dependent, okadaic acid-resistant phosphatase activity on a synthetic phosphorylated peptide, RRA(pT)VA, indicating that Pph1 is a PP2C phosphatase. Pph1-expression was observed under both vegetative and developmental conditions, but peaked during early aggregation. A pph1 null mutant showed defects during late vegetative growth, swarming and glycerol spore formation. Under starvation-induced developmental conditions, the mutant showed reduced aggregation and failure to form fruiting bodies with viable spores. Using the yeast two-hybrid system, we have observed a strong interaction between Pph1 and the M. xanthus protein kinase Pkn5, a negative effector of development. These results suggest a functional link between a Pkn2-type protein kinase and a PP2C phosphatase.

  7. Anatomical distribution of diarrhetic shellfish poisoning (DSP) toxins in the mussel Mytilus galloprovincialis.

    Science.gov (United States)

    Blanco, Juan; Mariño, Carmen; Martín, Helena; Acosta, Carmen P

    2007-12-15

    The aim of this work was to shed light on the anatomical distribution of diarrhetic shellfish poisoning (DSP) toxins in the mussel Mytilus galloprovincialis and to determine any possible changes undergone during the depuration process. To this end, the distribution of two DSP toxins--okadaic acid and DTX2--and some of their derivatives were studied by means of HPLC/MS at different stages of the depuration process. Mussels were collected from mussel farms located in the Galician Rías and they were collected under three types of circumstances: (a) while ingesting toxic phytoplankton cells; (b) 1 week after the toxic cells had disappeared from the water; and (c) after ca. 2 months of depuration. Additionally, in case (b), the distribution among tissues was checked every week over a depuration period of 35 days in the laboratory. DSP toxins were only detected in non-visceral tissues when the extracts were concentrated 20-fold and, even in these cases, the concentrations found were very low. When the maximum possible contribution of non-visceral tissues was computed, taking into account the technique's detection limits and tissue weight, no relevant contribution to the toxin burden of non-visceral tissues was found at any stage of depuration, with the maximum possible contributions usually below 7%. The concentrated samples analysed showed that the actual contribution in all the cases studied was, in fact, less than 1% of the total toxin burden. These findings suggest that (1) when analytical methods are used to monitor DSP toxic mussels, non-visceral tissues should be assumed to be free of toxins in order to precisely compute the toxin concentration of the whole mass of edible tissues and (2) when studying the accumulation kinetics of DSP toxins, transference from the digestive gland to other tissues should not be taken into account, as the other tissues do not contain relevant amounts of DSP toxins.

  8. Mutant TDP-43 deregulates AMPK activation by PP2A in ALS models.

    Directory of Open Access Journals (Sweden)

    Nirma D Perera

    Full Text Available Bioenergetic abnormalities and metabolic dysfunctionoccur in amyotrophic lateral sclerosis (ALS patients and genetic mouse models. However, whether metabolic dysfunction occurs earlyin ALS pathophysiology linked to different ALS genes remains unclear.Here, we investigatedAMP-activated protein kinase (AMPK activation, which is a key enzyme induced by energy depletion and metabolic stress, inneuronal cells and mouse models expressing mutantsuperoxide dismutase 1 (SOD1or TAR DNA binding protein 43 (TDP-43 linked to ALS.AMPKphosphorylation was sharply increased in spinal cords of transgenic SOD1G93A mice at disease onset and accumulated incytoplasmic granules in motor neurons, but not in pre-symptomatic mice. AMPK phosphorylation also occurred in peripheraltissues, liver and kidney, in SOD1G93A mice at disease onset, demonstrating that AMPK activation occurs late and is not restricted to motor neurons. Conversely, AMPK activity was drastically diminished in spinal cords and brains of presymptomatic and symptomatictransgenic TDP-43A315T mice and motor neuronal cells expressing different TDP-43 mutants. We show that mutant TDP-43 induction of the AMPK phosphatase,protein phosphatase 2A (PP2A, is associated with AMPK inactivation in these ALS models. Furthermore, PP2A inhibition by okadaic acid reversed AMPK inactivation by mutant TDP-43 in neuronal cells. Our results suggest that mutant SOD1 and TDP-43 exert contrasting effects on AMPK activation which may reflect key differences in energy metabolism and neurodegeneration in spinal cords of SOD1G93A and TDP-43A315T mice. While AMPK activation in motor neurons correlateswith progressionin mutant SOD1-mediated disease, AMPK inactivation mediated by PP2Ais associated withmutant TDP-43-linked ALS.

  9. Mutant TDP-43 deregulates AMPK activation by PP2A in ALS models.

    Directory of Open Access Journals (Sweden)

    Nirma D Perera

    Full Text Available Bioenergetic abnormalities and metabolic dysfunction occur in amyotrophic lateral sclerosis (ALS patients and genetic mouse models. However, whether metabolic dysfunction occurs early in ALS pathophysiology linked to different ALS genes remains unclear. Here, we investigated AMP-activated protein kinase (AMPK activation, which is a key enzyme induced by energy depletion and metabolic stress, in neuronal cells and mouse models expressing mutant superoxide dismutase 1 (SOD1 or TAR DNA binding protein 43 (TDP-43 linked to ALS. AMPK phosphorylation was sharply increased in spinal cords of transgenic SOD1G93A mice at disease onset and accumulated in cytoplasmic granules in motor neurons, but not in presymptomatic mice. AMPK phosphorylation also occurred in peripheral tissues, liver and kidney, in SOD1G93A mice at disease onset, demonstrating that AMPK activation occurs late and is not restricted to motor neurons. Conversely, AMPK activity was drastically diminished in spinal cords and brains of presymptomatic and symptomatic transgenic TDP-43A315T mice and motor neuronal cells expressing different TDP-43 mutants. We show that mutant TDP-43 induction of the AMPK phosphatase, protein phosphatase 2A (PP2A, is associated with AMPK inactivation in these ALS models. Furthermore, PP2A inhibition by okadaic acid reversed AMPK inactivation by mutant TDP-43 in neuronal cells. Our results suggest that mutant SOD1 and TDP-43 exert contrasting effects on AMPK activation which may reflect key differences in energy metabolism and neurodegeneration in spinal cords of SOD1G93A and TDP-43A315T mice. While AMPK activation in motor neurons correlates with progression in mutant SOD1-mediated disease, AMPK inactivation mediated by PP2A is associated with mutant TDP-43-linked ALS.

  10. The Nrf1 CNC-bZIP protein is regulated by the proteasome and activated by hypoxia.

    Science.gov (United States)

    Chepelev, Nikolai L; Bennitz, Joshua D; Huang, Ting; McBride, Skye; Willmore, William G

    2011-01-01

    Nrf1 (nuclear factor-erythroid 2 p45 subunit-related factor 1) is a transcription factor mediating cellular responses to xenobiotic and pro-oxidant stress. Nrf1 regulates the transcription of many stress-related genes through the electrophile response elements (EpREs) located in their promoter regions. Despite its potential importance in human health, the mechanisms controlling Nrf1 have not been addressed fully. We found that proteasomal inhibitors MG-132 and clasto-lactacystin-β-lactone stabilized the protein expression of full-length Nrf1 in both COS7 and WFF2002 cells. Concomitantly, proteasomal inhibition decreased the expression of a smaller, N-terminal Nrf1 fragment, with an approximate molecular weight of 23 kDa. The EpRE-luciferase reporter assays revealed that proteasomal inhibition markedly inhibited the Nrf1 transactivational activity. These results support earlier hypotheses that the 26 S proteasome processes Nrf1 into its active form by removing its inhibitory N-terminal domain anchoring Nrf1 to the endoplasmic reticulum. Immunoprecipitation demonstrated that Nrf1 is ubiquitinated and that proteasomal inhibition increased the degree of Nrf1 ubiquitination. Furthermore, Nrf1 protein had a half-life of approximately 5 hours in COS7 cells. In contrast, hypoxia (1% O(2)) significantly increased the luciferase reporter activity of exogenous Nrf1 protein, while decreasing the protein expression of p65, a shorter form of Nrf1, known to act as a repressor of EpRE-controlled gene expression. Finally, the protein phosphatase inhibitor okadaic acid activated Nrf1 reporter activity, while the latter was repressed by the PKC inhibitor staurosporine. Collectively, our data suggests that Nrf1 is controlled by several post-translational mechanisms, including ubiquitination, proteolytic processing and proteasomal-mediated degradation as well as by its phosphorylation status. © 2011 Chepelev et al.

  11. Rapid tumor necrosis and massive hemorrhage induced by bevacizumab and paclitaxel combination therapy in a case of advanced breast cancer

    Directory of Open Access Journals (Sweden)

    Ono M

    2013-10-01

    Full Text Available Mayu Ono, Tokiko Ito, Toshiharu Kanai, Koichi Murayama, Hiroshi Koyama, Kazuma Maeno, Yasuhiro Mochizuki, Asumi Iesato, Toru Hanamura, Toshihiro Okada, Takayuki Watanabe, Ken-ichi ItoDivision of Breast and Endocrine Surgery, Department of Surgery (II, Shinshu University School of Medicine, Matsumoto, JapanAbstract: Bevacizumab when combined with chemotherapy exerts significant activity against many solid tumors through tumor angiogenesis inhibition; however, it can induce severe side effects. We report the rare case of a 27-year-old premenopausal woman with locally advanced breast cancer that was marked by rapid tumor necrosis followed by massive hemorrhage shortly after bevacizumab and paclitaxel administration. On the basis of histopathological examination of a biopsy specimen and computed tomography findings, she was diagnosed with stage IV estrogen and progesterone receptor-negative and human epidermal growth factor receptor type 2-positive breast cancer with multiple organ metastases when she had entered gestational week 24. Cyclophosphamide, Adriamycin®, fluorouracil therapy was initiated, but multiple liver metastases continued to progress. A healthy fetus was delivered by induced delivery and trastuzumab-based treatment was initiated. Although the multiple liver metastases were controlled successfully by trastuzumab combined with paclitaxel, the primary tumor continued to expand even after subsequent administration of three other treatment regimens including anti-human epidermal growth factor receptor type 2 agents and cytotoxic drugs. To inhibit primary tumor growth, a combination therapy with paclitaxel and bevacizumab was subsequently initiated. Following therapy initiation, however, the large tumor occupying the patient's entire left breast became necrotic and ulcerated rapidly. Furthermore, massive hemorrhage from the tumor occurred 5 weeks after bevacizumab-based therapy initiation. Although hemostasis was achieved by manual

  12. Label-free voltammetric aptasensor for the sensitive detection of microcystin-LR using graphene-modified electrodes.

    Science.gov (United States)

    Eissa, Shimaa; Ng, Andy; Siaj, Mohamed; Zourob, Mohammed

    2014-08-05

    The development of successful biosensing platforms is highly dependent upon the biorecognition properties of the recognition receptor and the sensitivity of the transducer of the binding signal. The integration of the high affinity and specificity of DNA aptamers with the unique properties of the carbon nanomaterial graphene offers an excellent avenue for sensitive and selective biosensing architectures. In this work, a highly sensitive and selective aptasensor which utilizes an unlabeled DNA aptamer assembled on a graphene electrode for microcystin-LR detection was developed. A facile strategy was used for the aptasensor fabrication on the basis of the noncovalent assembly of DNA aptamer on graphene-modified screen printed carbon electrodes. Assembly of the DNA aptamer on the graphene-modified electrodes caused a marked drop in the square wave voltammetric reduction signal of the [Fe(CN)6](4-/3-) redox couple. The presence of microcystin-LR, on the other hand, caused a dose-responsive increase in peak current, allowing the quantification of microcystin-LR through the measurement of peak current change. Under optimal conditions, the detection limit of the developed aptasensor was 1.9 pM in buffer, a concentration much lower than those offered by previously reported biosensors for microcystin-LR. The developed aptasensor also exhibited excellent selectivity for microcystin-LR with no detectable cross-reactivity to okadaic acid, microcystin-LA, and microcystin-YR. Moreover, the proposed aptasensor has been applied for the analysis of spiked tap water and fish samples showing good recovery percentages. This novel, simple, high-performance, and low-cost detection platform would facilitate the routine monitoring of microcystin-LR in real samples.

  13. Light intensity regulation of cab gene transcription is signaled by the redox state of the plastoquinone pool

    Energy Technology Data Exchange (ETDEWEB)

    Escoubas, J.M.; Lomas, M.; LaRoche, J. [Brookhaven National Lab., Upton, NY (United States)] [and others

    1995-10-24

    The eukaryotic green alga Dunaliella tertiolecta acclimates to decreased growth irradiance by increasing cellular levels of light-harvesting chlorophyll protein complex apoproteins associated with photosystem II (LHCIIs), whereas increased growth irradiance elicits the opposite response. Nuclear run-on transcription assays and measurements of cab mRNA stability established that light intensity-dependent changes in LHCII are controlled at the level of transcription. cab gene transcription in high-intensity light was partially enhanced by reducing plastoquinone with 3-(3,4-dichlorophenyl)-1,1-dimethyl urea (DCMU), whereas it was repressed in low-intensity light by partially inhibiting the oxidation of plastoquinol with 2,5-dibromo-3-methyl-6-isopropyl-p-benzoquinone (DBMIB). Uncouplers of photosynthetic electron transport and inhibition of water splitting had no effect on LHCII levels. These results strongly implicate the redox state of the plastoquinone pool in the chloroplast as a photon-sensing system that is coupled to the light-intensity regulation of nuclear-encoded cab gene transcription. The accumulation of cellular chlorophyll at low-intensity light can be blocked by cytoplasmically directed phosphatase inhibitors, such as okadaic acid, microcystin L-R, and tautomycin. Gel mobility-shift assays revealed that cells grown in high-intensity light contained proteins that bind to the promoter region of a cab gene carrying sequences homologous to higher plant light-responsive elements. On the basis of these experimental results, we propose a model for a light intensity signaling system where cab gene expression is reversibly repressed by a phosphorylated factor coupled to the redox status of plastoquinone through a chloroplast protein kinase. 54 refs., 5 figs.

  14. The RCN1-encoded A subunit of protein phosphatase 2A increases phosphatase activity in vivo

    Science.gov (United States)

    Deruere, J.; Jackson, K.; Garbers, C.; Soll, D.; Delong, A.; Evans, M. L. (Principal Investigator)

    1999-01-01

    Protein phosphatase 2A (PP2A), a heterotrimeric serine/threonine-specific protein phosphatase, comprises a catalytic C subunit and two distinct regulatory subunits, A and B. The RCN1 gene encodes one of three A regulatory subunits in Arabidopsis thaliana. A T-DNA insertion mutation at this locus impairs root curling, seedling organ elongation and apical hypocotyl hook formation. We have used in vivo and in vitro assays to gauge the impact of the rcn1 mutation on PP2A activity in seedlings. PP2A activity is decreased in extracts from rcn1 mutant seedlings, and this decrease is not due to a reduction in catalytic subunit expression. Roots of mutant seedlings exhibit increased sensitivity to the phosphatase inhibitors okadaic acid and cantharidin in organ elongation assays. Shoots of dark-grown, but not light-grown seedlings also show increased inhibitor sensitivity. Furthermore, cantharidin treatment of wild-type seedlings mimics the rcn1 defect in root curling, root waving and hypocotyl hook formation assays. In roots of wild-type seedlings, RCN1 mRNA is expressed at high levels in root tips, and accumulates to lower levels in the pericycle and lateral root primordia. In shoots, RCN1 is expressed in the apical hook and the basal, rapidly elongating cells in etiolated hypocotyls, and in the shoot meristem and leaf primordia of light-grown seedlings. Our results show that the wild-type RCN1-encoded A subunit functions as a positive regulator of the PP2A holoenzyme, increasing activity towards substrates involved in organ elongation and differential cell elongation responses such as root curling.

  15. Waveform generation is controlled by phosphorylation and swimming direction is controlled by Ca2+ in sperm from the mosquito Culex quinquefasciatus.

    Science.gov (United States)

    Thaler, Catherine D; Miyata, Haruhiko; Haimo, Leah T; Cardullo, Richard A

    2013-12-01

    Most animal sperm are quiescent in the male reproductive tract and become activated after mixing with accessory secretions from the male and/or female reproductive tract. Sperm from the mosquito Culex quinquefasciatus initiate flagellar motility after mixing with male accessory gland components, and the sperm flagellum displays three distinct motility patterns over time: a low amplitude, a long wavelength form (Wave A), a double waveform consisting of two superimposed waveforms over the length of the flagellum (Wave B), and finally, a single helical waveform that propels the sperm at high velocity (Wave C). This flagellar behavior is replicated by treating quiescent sperm with trypsin. When exposed to either broad spectrum or tyrosine kinase inhibitors, sperm activated by accessory gland secretions exhibited motility through Wave B but were unable to progress to Wave C. The MEK1/2 inhibitor UO126 and the ERK1/2 inhibitor FR180204 each blocked the transition from Wave B to Wave C, indicating a role for MAPK activity in the control of waveform and, accordingly, progressive movement. Furthermore, a MAPK substrate antibody stained the flagellum of activated sperm. In the absence of extracellular Ca(2+), a small fraction of sperm swam backwards, whereas most could not be activated by either accessory glands or trypsin and were immotile. However, the phosphatase inhibitor okadaic acid in the absence of extracellular Ca(2+) induced all sperm to swim backwards with a flagellar waveform similar to Wave A. These results indicate that flagellar waveform generation and direction of motility are controlled by protein phosphorylation and Ca(2+) levels, respectively.

  16. Effect of ozonation and γ-irradiation on post-harvest decontamination of mussels (Mytillus galloprovincialis) containing diarrhetic shellfish toxins.

    Science.gov (United States)

    Louppis, A P; Katikou, P; Georgantelis, D; Badeka, A V; Kontominas, M G

    2011-12-01

    Contamination of shellfish with diarrhetic shellfish poisoning (DSP) toxins readily occurs during algal blooms. Such phenomena raise important public health concerns and thus comprise a constant challenge to shellfish farmers, the seafood industry and health services, considering the increasing occurrence of toxic episodes around the world. To avoid the detrimental effects of such episodes, research has focused on the use of various detoxification methodologies that should be rapid, efficient, easy to apply, and will not alter the quality and sensory properties of shellfish. In the present study, both ozonation (15 mg kg(-1) for 6 h) and γ-irradiation (6 kGy) were utilised in order to reduce the toxin content of contaminated shucked mussels, collected during the DSP episodes of 2007 and 2009 in Greece. DSP toxicity was monitored using the mouse bioassay (MBA) whilst the determination of toxin content of the okadaic acid (OA) group (both free and esterified forms) was carried out by LC/MS/MS analysis. Toxin reduction using γ-irradiation was in the range of 12-36%, 8-53% and 10-41% for free OA, OA esters and total OA, respectively. The appearance and texture of irradiated mussels deteriorated, pointing to a low potential for commercial use of this method. Ozonation of mussels resulted in toxin reduction in the range of 6-100%, 25-83% and 21-66% for free OA, OA esters and total OA, respectively. Reduction of OA content was substantially higher in homogenised mussel tissue compared with that of whole shucked mussels. In addition, differences detected with regard to quality parameters (TBA, sensory attributes) between ozonated and control mussels were not considerable. Even though varying percentage reductions in OA and its derivatives were achieved using ozonation under specific experimental conditions tested, it is postulated that upon optimisation ozonation may have the potential for post-harvest commercial DSP detoxification of shucked mussels.

  17. PREFACE: Fourth International Symposium on Atomic Technology

    Science.gov (United States)

    Okada, Shigefumi

    2010-04-01

    The International Symposium on Atomic Technology (ISAT) is held every year. The 4th Symposium (ISAT-4) was held on November 18-19, 2009 at the Seaside Hotel MAIKO VILLA KOBE, Kobe City, Japan presided by the "Atomic Technology Project". The ISAT-4 symposium was intended to offer a forum for the discussion on the latest progress in the atomic technologies. The symposium was attended by 107 delegates. There were 10 invited and 6 oral presentations. The number of poster presentations was 69. From all the contributions, 22 papers selected through review process are contained in this volume. The "Atomic Technology Project" was started in 2006 as a joint project of three institutions; (1) the Center for Atomic and Molecular Technologies, Graduate School of Engineering, Osaka University (CAMT), (2) the Tsukuba Research Center for Interdisciplinary Materials Science, Graduate School of Pure and Applied Sciences, University of Tsukuba (TIMS) and (3) the Polyscale Technology Research Center, Research Institute for Science and Technology, Tokyo University of Science (PTRC), each of which were independently pursuing nano-technologies and was developing atomic scale operation and diagnostics, functional materials, micro processing and device. The project is funded by the Ministry of Education, Culture, Sports, Science and Technology of Japan. The goal of the project is to contribute to the development of atomic-scale science and technologies such as functional molecules, biomaterials, and quantum functions of atomic-scale structures. Shigefumi Okada Conference Chair Center for Atomic and Molecular Technologies, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita-city, Osaka 565-0871, Japan. Conference photograph Kobe photograph

  18. Effects of in vitro exposure to diarrheic toxin producer Prorocentrum lima on gene expressions related to cell cycle regulation and immune response in Crassostrea gigas.

    Directory of Open Access Journals (Sweden)

    Reyna de Jesús Romero-Geraldo

    Full Text Available BACKGROUND: Crassostrea gigas accumulates diarrheic shellfish toxins (DSP associated to Prorocentrum lima of which Okadaic acid (OA causes specific inhibitions of serine and threonine phosphatases 1 and 2A. Its toxic effects have been extensively reported in bivalve mollusks at cellular and physiological levels, but genomic approaches have been scarcely studied. METHODOLOGY/PRINCIPAL FINDINGS: Acute and sub-chronic exposure effects of P. lima were investigated on farmed juvenile C. gigas (3-5 mm. The Pacific oysters were fed with three dinoflagellate concentrations: 0.3, 3, and 30 ×10(3 cells mL-1 along with a nontoxic control diet of Isochrysis galbana. The effects of P. lima on C. gigas were followed by analyzing expression levels of a total of four genes, three involved in cell cycle regulation and one in immune response by polymerase chain reaction and real time quantitative PCR, where changes in time and cell concentration were found. The highest expression levels were found in oysters fed 3 × 10(3 cells mL-1 at 168 h for the cycle regulator p21 protein (9 fold, chromatin assembly factor 1 p55 subunit (8 fold, elongation factor 2 (2 fold, and lipopolysaccharide/β-1, 3 glucan binding protein (13 fold above base line. Additionally, the transcript level of all the genes decreased in oysters fed wich the mixed diet 30 × 10(3 cells mL-1 of dinoflagellate after 72 h and was lowest in the chromatin assembly factor 1 p55 subunit (0.9 fold below baseline. CONCLUSIONS: On C. gigas the whole cell ingestion of P lima caused a clear mRNA modulation expression of the genes involved in cell cycle regulation and immune system. Over-expression could be related to DNA damage, disturbances in cell cycle continuity, probably a genotoxic effect, as well as an activation of its innate immune system as first line of defense.

  19. Participatory diagnostic survey of constraints to youth involvement in cocoa production in Cross River State of Nigeria

    Directory of Open Access Journals (Sweden)

    Adeogun Stephen O.

    2015-01-01

    Full Text Available Youth's roles in cocoa production cannot be undermined considering the need to ensure succession plan, industry success, and guaranteed future. The study diagnosed constraints hindering youth involvement in cocoa production in Cross River State, Nigeria. A simple random sampling technique was used to select 20% of cocoa producing Local Government Areas (LGAs in Cross River State resulting in three LGAs. To obtain a sample for the study, snowball techniques were used to select 45 youths, who are cocoa farmers, per LGA to give sample size of 135 cocoa farmers. The findings revealed that the majority of respondents (95% were male, and between ages 21 and 40 years (82.5%. Regarding educational status, the majority of respondents (66.7% have secondary school education while few (5% realized above 2,500USD/ha from cocoa farm annually. The study revealed that respondents agreed that there are numerous constraints militating against youth involvement in cocoa farming. Eight major constraints identified among these constraints are youth rural-urban migration, high cost of cocoa production due to incidence of pests and diseases and youth interest in commercial motorcycle "Okada" business. Respondents ranked non-availability of basic amenities, rigorous nature of cocoa farming and youth interest in commercial motorcycle business first, second and third respectively. Stakeholders identified during Focus Group Discussion (FGD included STCP/IITA, SOCCODEVI and ADP. STCP/IITA and ADP were however the closest to the cocoa farming community. The study concluded that there are constraints discouraging youth involvement in cocoa farming. Hence, to ensure good succession plans, the study recommended that all stakeholders must make effort to address the various constraints identified by respondents.

  20. Thermal Infrared Imager on Hayabusa2: Science and Development

    Science.gov (United States)

    Okada, Tatsuaki

    2015-04-01

    Thermal Infrared Imager TIR was developed and calibrated for Haya-busa2 asteroid explorer, aiming at the investigation of thermo-physical properties of C-class near-Earth sub-km sized asteroid (162173) 1999JU3. TIR is based on the 2D micro-bolometer array with germani-um lens to image the surface of asteroid in 8 to 12 μm wavelength (1), measuring the thermal emission off the asteroid surface. Its field of view is 16° x 12° with 328 x 248 pixels. At least 40 (up to 100) images will be taken during asteroid rotation once a week, mainly from the Home Position which is about 20km sunward from asteroid surface. Therefore TIR will image the whole asteroid with spatial resolution of scien-tific objectives of TIR include the mapping of asteroid surface condi-tions (regional distribution of thermal inertia), since the surface physical conditions are strongly correlated with thermal inertia. It is so informa-tive on understanding the re-accretion or surface sedimentation process-es of the asteroid to be the current form. TIR data will be used for searching for those sites having the typical particle size of 1mm for best sample collection, and within the proper thermal condition for space-craft safe operation. After launch of Hayabusa2, TIR has been tested successfully, covering from -100 to 150 °C using a single parameter settings (2). This implies that TIR is actually able to map the surface other than the sunlit areas. Performance of TIR was found basically the same as those in the pre-launch test, when the temperature of TIR is well controlled. References: (1) Fukuhara T. et al., (2011) Earth Planet. Space 63, 1009-1018; (2) Okada T. et al., (2015) Lunar Planet. Sci. Conf. 46, #1331.

  1. Scenario Based Approach for Multiple Source Tsunami Hazard Assessment for Sines, Portugal

    Science.gov (United States)

    Wronna, Martin; Omira, Rachid; Baptista, Maria Ana

    2015-04-01

    In this paper, we present a scenario-based approach for tsunami hazard assessment for the city and harbour of Sines, Portugal one the test-sites of project ASTARTE. Sines holds one of the most important deep-water ports which contains oil-bearing, petrochemical, liquid bulk, coal and container terminals. The port and its industrial infrastructures are facing the ocean to the southwest facing the main seismogenic sources. This work considers two different seismic zones: the Southwest Iberian Margin and the Gloria Fault. Within these two regions, a total of five scenarios were selected to assess tsunami impact at the test site. These scenarios correspond to the worst-case credible scenario approach based upon the largest events of the historical and paleo tsunami catalogues. The tsunami simulations from the source area towards the coast is carried out using NSWING a Non-linear Shallow Water Model With Nested Grids. The code solves the non-linear shallow water equations using the discretization and explicit leap-frog finite difference scheme, in a Cartesian or Spherical frame. The initial sea surface displacement is assumed to be equal to the sea bottom deformation that is computed by Okada equations. Both uniform and non-uniform slip conditions are used. The presented results correspond to the models using non-uniform slip conditions. In this study, the static effect of tides is analysed for three different tidal stages MLLW (mean lower low water) MSL (mean sea level) and MHHW (mean higher high water). For each scenario, inundation is described by maximum values of wave height, flow depth, drawdown, run-up and inundation distance. Synthetic waveforms are computed at virtual tide gages at specific locations outside and inside the harbour. The final results consist of Aggregate Scenario Maps presented for the different inundation parameters. This work is funded by ASTARTE - Assessment, Strategy And Risk Reduction for Tsunamis in Europe - FP7-ENV2013 6.4-3, Grant 603839

  2. Lipophilic marine toxins discovered in the Bohai Sea using high performance liquid chromatography coupled with tandem mass spectrometry.

    Science.gov (United States)

    Liu, Yang; Yu, Ren-Cheng; Kong, Fan-Zhou; Li, Chen; Dai, Li; Chen, Zhen-Fan; Zhou, Ming-Jiang

    2017-09-01

    Some dinoflagellates can produce lipophilic marine toxins, which pose potent threats to seafood consumers. In the Bohai Sea, an important semi-closed inland sea with intensive mariculture industry in China, there is little knowledge concerning lipophilic marine toxins and their potential threats. In this study, net-concentrated phytoplankton samples were periodically collected from 5 typical mariculture zones around the Bohai Sea, including Laishan (LS), Laizhou (LZ), Hangu (HG), Qinhuangdao (QHD) and Huludao (HLD) in 2013 and 2014, and a method using high performance liquid chromatography (HPLC) coupled with a Q-Trap mass spectrometer was applied to analyze seven representative lipophilic marine toxins, including okadaic acid (OA), dinophysistoxin-1 (DTX1), pectenotoxin-2 (PTX2), yessotoxin (YTX), azaspiracid-1 (AZA1), gymnodimine (GYM), and 13-desmethyl spirolide C (desMeC). The method had high sensitivity and repeatability, and exhibited satisfactory recoveries for most of the lipophilic marine toxins (92.1-108%) except for AZA1 (65.8-68.9%). Nearly all the lipophilic marine toxins could be detected in phytoplankton samples from the Bohai Sea. OA, DTX1 and PTX2 were predominant components and present in most of the phytoplankton samples. The maximum content of lipophilic marine toxin in phytoplankton samples concentrated from seawater (OA 464 pg L(-1); DTX1 783 pg L(-1); YTX 86.6 pg L(-1); desMeC 15.6 pg L(-1); PTX2 1.11 × 10(3) pg L(-1)) appeared in June 2014. Based on toxins present in phytoplankton samples, it is implied that seafood in the Bohai Sea is more likely to be contaminated by OA group and PTX group toxins, and spring is the high-risk season for toxin contamination. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Occurrence and distribution of marine natural organic pollutants: Lipophilic marine algal toxins in the Yellow Sea and the Bohai Sea, China.

    Science.gov (United States)

    Chen, Junhui; Han, Tongzhu; Li, Xiaotong; He, Xiuping; Wang, Yanlong; Chen, Farong; Song, Xincheng; Zhou, Deshan; Wang, Xiaoru

    2017-09-05

    For the first time, the composition, concentration and distribution characteristics of typical lipophilic marine algal toxins (LMATs) are investigated in surface seawater, suspended particulate matter (SPM) and sediments from the Yellow Sea and the Bohai Sea, China. Pectenotoxin-2 (PTX2) and okadaic acid (OA) were detected in offshore surface seawater samples (n=67) of the Yellow and Bohai Seas, and PTX2 was found in higher concentrations than OA. The concentrations of PTX2 were between 0.49 and 14.14ng/L. OA, dinophysistoxin-1(DTX1), PTX2 and gymnodimine (GYM) were detected in the nearshore surface seawater samples (n=20) of the Haizhou Bay of the Yellow Sea. OA concentrations were between 11.47 and 55.85ng/L. There was a large degree of variation in the concentrations of DTX1, from

  4. Inorganic lead may inhibit neurite development in cultured rat hippocampal neurons through hyperphosphorylation.

    Science.gov (United States)

    Kern, M; Audesirk, G

    1995-09-01

    Inorganic lead inhibits neurite initiation in cultured rat hippocampal neurons at concentrations as low as 100 nM. Conflicting reports suggest that Pb2+ may stimulate or inhibit protein kinase C, adenylyl cyclase, phosphodiesterase, and calmodulin, or increase intracellular free Ca2+ concentrations. Therefore, Pb2+ may alter the activities of Ca2+/calmodulin-dependent protein kinase (CaM kinase) or protein kinases C or A. We cultured rat hippocampal neurons in 100 nM PbCI2 alone or in combination with kinase or calmodulin inhibitors. Inhibiting protein kinase C with calphostin C exacerbated the inhibition of neurite initiation caused by PbCI2, but inhibiting protein kinase A with KT5720, CaM kinase with KN62, or calmodulin with calmidazolium completely reversed the effects of PbCI2. These results indicate that Pb2+ may inhibit neurite initiation by inappropriately stimulating protein phosphorylation by CaM kinase or cyclic AMP-dependent protein kinase (PKA), possibly by stimulating calmodulin. This hypothesis is supported by findings that other treatments that should increase protein phosphorylation (okadaic acid, a protein phosphatase inhibitor, and Sp-cAMPS, a PKA activator) also reduced neurite initiation. Whole-cell intracellular free Ca2+ ion concentrations were not significantly altered by 100 nM PbCI2 at 4, 12, 24, or 48 hr. Therefore, the hypothesized stimulatory effects of Pb2+ exposure on calmodulin, CaM kinase, or PKA are probably not caused by increases in whole-cell intracellular free Ca2+, but may be attributable either to intracellular Pb2+ or to localized increases in [Ca2+]in that are not reflected in whole-cell measurements.

  5. Protein phosphatases decrease their activity during capacitation: a new requirement for this event.

    Directory of Open Access Journals (Sweden)

    Janetti R Signorelli

    Full Text Available There are few reports on the role of protein phosphatases during capacitation. Here, we report on the role of PP2B, PP1, and PP2A during human sperm capacitation. Motile sperm were resuspended in non-capacitating medium (NCM, Tyrode's medium, albumin- and bicarbonate-free or in reconstituted medium (RCM, NCM plus 2.6% albumin/25 mM bicarbonate. The presence of the phosphatases was evaluated by western blotting and the subcellular localization by indirect immunofluorescence. The function of these phosphatases was analyzed by incubating the sperm with specific inhibitors: okadaic acid, I2, endothall, and deltamethrin. Different aliquots were incubated in the following media: 1 NCM; 2 NCM plus inhibitors; 3 RCM; and 4 RCM plus inhibitors. The percent capacitated sperm and phosphatase activities were evaluated using the chlortetracycline assay and a phosphatase assay kit, respectively. The results confirm the presence of PP2B and PP1 in human sperm. We also report the presence of PP2A, specifically, the catalytic subunit and the regulatory subunits PR65 and B. PP2B and PP2A were present in the tail, neck, and postacrosomal region, and PP1 was present in the postacrosomal region, neck, middle, and principal piece of human sperm. Treatment with phosphatase inhibitors rapidly (≤1 min increased the percent of sperm depicting the pattern B, reaching a maximum of ∼40% that was maintained throughout incubation; after 3 h, the percent of capacitated sperm was similar to that of the control. The enzymatic activity of the phosphatases decreased during capacitation without changes in their expression. The pattern of phosphorylation on threonine residues showed a sharp increase upon treatment with the inhibitors. In conclusion, human sperm express PP1, PP2B, and PP2A, and the activity of these phosphatases decreases during capacitation. This decline in phosphatase activities and the subsequent increase in threonine phosphorylation may be an important

  6. A longitudinal, event-related potential pilot study of adult obsessive-compulsive disorder with 1-year follow-up

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    Yamamuro K

    2016-09-01

    Full Text Available Kazuhiko Yamamuro,1 Koji Okada,2 Naoko Kishimoto,1 Toyosaku Ota,1 Junzo Iida,3 Toshifumi Kishimoto1 1Department of Psychiatry, Nara Medical University School of Medicine, 2Department of Psychiatry, Jingumaecocorono-Clinic, 3Faculty of Nursing, Nara Medical University School of Medicine, Kashihara, Japan Aim: Earlier brain imaging research studies have suggested that brain abnormalities in obsessive-compulsive disorder (OCD normalize as clinical symptoms improve. However, although many studies have investigated event-related potentials (ERPs in patients with OCD compared with healthy control subjects, it is currently unknown whether ERP changes reflect pharmacological and psychotherapeutic effects. As such, the current study examined the neurocognitive components of OCD to elucidate the pathophysiological abnormalities involved in the disorder, including the frontal-subcortical circuits.Methods: The Yale-Brown Obsessive-Compulsive Scale was used to evaluate 14 adult patients with OCD. The present study also included ten age-, sex-, and IQ-matched controls. The P300 and mismatch negativity (MMN components during an auditory oddball task at baseline for both groups and after 1 year of treatment for patients with OCD were measured.Results: Compared with controls, P300 amplitude was attenuated in the OCD group at Cz and C4 at baseline. Pharmacotherapy and psychotherapy treatment for 1 year reduced OCD symptomology. P300 amplitude after 1 year of treatment was significantly increased, indicating normalization compared with baseline at Fz, Cz, C3, and C4. We found no differences in P300 latency, MMN amplitude, or MMN latency between baseline and after one year of treatment.Conclusion: ERPs may be a useful tool for evaluating pharmacological and cognitive behavioral therapy in adult patients with OCD. Keywords: obsessive-compulsive disorder, event-related potentials, P300, mismatch negativity, improvement

  7. Aberrant calcium/calmodulin-dependent protein kinase II (CaMKII) activity is associated with abnormal dendritic spine morphology in the ATRX mutant mouse brain.

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    Shioda, Norifumi; Beppu, Hideyuki; Fukuda, Takaichi; Li, En; Kitajima, Isao; Fukunaga, Kohji

    2011-01-05

    In humans, mutations in the gene encoding ATRX, a chromatin remodeling protein of the sucrose-nonfermenting 2 family, cause several mental retardation disorders, including α-thalassemia X-linked mental retardation syndrome. We generated ATRX mutant mice lacking exon 2 (ATRX(ΔE2) mice), a mutation that mimics exon 2 mutations seen in human patients and associated with milder forms of retardation. ATRX(ΔE2) mice exhibited abnormal dendritic spine formation in the medial prefrontal cortex (mPFC). Consistent with other mouse models of mental retardation, ATRX(ΔE2) mice exhibited longer and thinner dendritic spines compared with wild-type mice without changes in spine number. Interestingly, aberrant increased calcium/calmodulin-dependent protein kinase II (CaMKII) activity was observed in the mPFC of ATRX(ΔE2) mice. Increased CaMKII autophosphorylation and activity were associated with increased phosphorylation of the Rac1-guanine nucleotide exchange factors (GEFs) T-cell lymphoma invasion and metastasis 1 (Tiam1) and kalirin-7, known substrates of CaMKII. We confirmed increased phosphorylation of p21-activated kinases (PAKs) in mPFC extracts. Furthermore, reduced protein expression and activity of protein phosphatase 1 (PP1) was evident in the mPFC of ATRX(ΔE2) mice. In cultured cortical neurons, PP1 inhibition by okadaic acid increased CaMKII-dependent Tiam1 and kalirin-7 phosphorylation. Together, our data strongly suggest that aberrant CaMKII activation likely mediates abnormal spine formation in the mPFC. Such morphological changes plus elevated Rac1-GEF/PAK signaling seen in ATRX(ΔE2) mice may contribute to mental retardation syndromes seen in human patients.

  8. Detection of Methicillin-Resistant Staphylococci Isolated from Food Producing Animals: A Public Health Implication

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    Etinosa O. Igbinosa

    2016-07-01

    Full Text Available The emergence of antibiotic-resistant bacteria in food animals is a potential public health concern. Staphylococci are a significant opportunistic pathogen both in humans and dairy cattle. In the present study, the genotypic characterization of methicillin-resistant staphylococcal strains recovered from dairy cattle in a rural community (Okada, Edo State, Nigeria was investigated. A total of 283 samples from cattle (137 milk samples and 146 nasal swabs were assessed between February and April 2015. Antimicrobial susceptibility was performed by Kirby-Bauer disc diffusion method. Polymerase chain reaction (PCR assay was employed for the detection of 16S rRNA, mecA and Panton-Valentine Leucocidinis (PVL genes. The staphylococcal strains were identified through partial 16S ribosomal ribonucleic acids (rRNA nucleotide sequencing, and Basic Local Alignment Search Tool (BLAST analysis of the gene sequence showed that the staphylococcal strains have 96%–100% similarity to Staphylococcus aureus (30, S. epidermidis (17, S. haemolyticus (15, S. saprophyticus (13, S. chromogenes (8, S. simulans (7, S. pseudintermedius (6 and S. xylosus (4. Resistance of 100% was observed in all Staphylococcus spp. against MET, PEN, CLN, CHL and SXT. Multi-drug resistant (MDR bacteria from nasal cavities and raw milk reveals 13 isolates were MDR against METR, PENR, AMXR, CLNR, CHLR, SXTR CLXR, KANR, ERYR, and VANR. Of all isolates, 100% harboured the mecA gene, while 30% of the isolates possess the PVL gene. All S. aureus harboured the PVL gene while other Staphylococcus spp. were negative for the PVL gene. The presence of methicillin-resistant Staphylococcus spp. isolates in dairy cattle is a potential public health risk and thus findings in this study can be used as a baseline for further surveillance.

  9. Notch-1 signaling activates NF-κB in human breast carcinoma MDA-MB-231 cells via PP2A-dependent AKT pathway.

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    Li, Li; Zhang, Jing; Xiong, Niya; Li, Shun; Chen, Yu; Yang, Hong; Wu, Chunhui; Zeng, Hongjuan; Liu, Yiyao

    2016-04-01

    Breast cancer has a high incidence in the world and is becoming a leading cause of death in female patients due to its high metastatic ability. High expression of Notch-1 and its ligand Jagged-1 correlates with poor prognosis in breast cancer. Our previous work has shown that Notch-1 signaling pathway upregulates NF-κB transcriptional activity and induces the adhesion, migration and invasion of human breast cancer cell line MDA-MB-231. However, the role of Notch-1 in NF-κB activation is still poorly understood. Here, we aim to understand the exact mechanism that Notch-1 regulates NF-κB activity. In MDA-MB-231 cells where Notch-1 is constitutively activated, the phosphorylation of p85 and AKT (Tyr308/Ser473) is upregulated, indicating PI3K/AKT pathway is activated. Notch-1 activation caused the increase of PP2A phosphorylation at Tyr307, indicating Notch-1 inhibits PP2A activity. NF-κB transcriptional activity was evaluated by dual-luciferase reporter assay, and the results showed that, while silencing of Notch-1, PP2A activity was upregulated and NF-κB activity was downregulated, whereas PP2A inhibitor okadaic acid (OA) restored NF-κB activity. Immunofluorescence and Western blots showed that OA treatment antagonized the decrease of p65 nuclear translocation caused by Notch-1 silencing. Moreover, OA treatment also upregulated MMP-2, MMP-9 and VEGF mRNA expression levels, indicating OA rescues Notch-1 silencing that caused low cell invasion. Taken together, our results suggest that Notch-1-activating PI3K/AKT/NF-κB pathway is PP2A dependent; PP2A may be a potential therapeutic target in breast cancer.

  10. Changes in visual function and thickness of macula after photodynamic therapy for age-related macular degeneration

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    Kyoko Okada

    2009-09-01

    Full Text Available Kyoko Okada, Mariko Kubota-Taniai, Masayasu Kitahashi, Takayuki Baba, Yoshinori Mitamura, Shuichi YamamotoDepartment of Ophthalmology and Visual Science, Chiba University Graduate School of Medicine, Chiba, JapanPurpose: To determine the correlation between the changes in the central retinal sensitivity and the changes in the foveal thickness (FT after photodynamic therapy (PDT for age-related macular degeneration (AMD.Methods: Nineteen eyes of 19 patients with choroidal neovasularizations (CNVs secondary to AMD were studied. The pretreatment values of the central retinal sensitivity determined by Micro Perimeter 1 (MP1; Nidek Technologies, best-corrected visual acuity (BCVA, and optical coherence tomography (OCT-determined FT were compared to the postoperative values at three and six months after PDT.Results: At six months, the retinal sensitivity within the central 10° was significantly improved (P = 0.02 and the FT was significantly thinner (P = 0.016. The BCVA, however, did not change significantly (P = 0.80. The changes in the retinal sensitivities were significantly correlated with the changes in the decrease in the FT (r = -0.59, P = 0.012 within the central 10° at six months after PDT.Conclusion: Significant improvements in retinal sensitivities within the central 10° and a decrease in FT were observed even though the BCVA was not significantly improved. The measurement of retinal sensitivity by MP1 may be a better method to assess central visual function than the conventional visual acuity after PDT.Keywords: age-related macular degeneration, fundus-related microperimetry, optical coherence tomography, photodynamic therapy

  11. EDITORIAL: Focus on Heavy Ions in Biophysics and Medical Physics FOCUS ON HEAVY IONS IN BIOPHYSICS AND MEDICAL PHYSICS

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    Durante, Marco

    2008-07-01

    include carcinogenesis, late degenerative tissue effects (including damage to the central nervous system), and hereditary effects. For these studies, microbeams represent an essential tool, considering that in space each cell in the human body will not experience more than one heavy-ion traversal. Both NASA and ESA are investing important resources in ground-based space radiation research programs, to reduce risk uncertainty and to develop countermeasures. For both cancer therapy and space radiation protection a better understanding of the effects of energetic heavy ions is needed. Physics should be improved, especially the measurements of nuclear fragmentation cross-sections, and the transport calculations. Biological effects need to be studied in greater detail, and clearly only understanding the mechanisms of heavy-ion induced biological damage will reduce the uncertainty on late effects in humans. This focus issue of New Journal of Physics aims to provide the state-of-the-art of the biophysics of energetic heavy ions and to highlight the areas where more research is urgently needed for therapy and the space program. Focus on Heavy Ions in Biophysics and Medical Physics Contents Heavy ion microprobes: a unique tool for bystander research and other radiobiological applications K O Voss, C Fournier and G Taucher-Scholz Heavy ions light flashes and brain functions: recent observations at accelerators and in spaceflight L Narici Clinical advantages of carbon-ion radiotherapy Hirohiko Tsujii, Tadashi Kamada, Masayuki Baba, Hiroshi Tsuji, Hirotoshi Kato, Shingo Kato, Shigeru Yamada, Shigeo Yasuda, Takeshi Yanagi, Hiroyuki Kato, Ryusuke Hara, Naotaka Yamamoto and Junetsu Mizoe Heavy-ion effects: from track structure to DNA and chromosome damage F Ballarini, D Alloni, A Facoetti and A Ottolenghi Shielding experiments with high-energy heavy ions for spaceflight applications C Zeitlin, S Guetersloh, L Heilbronn, J Miller, N Elkhayari, A Empl, M LeBourgeois, B W Mayes, L Pinsky

  12. Relocation of the Mw 6.4 July 1, 2009 earthquake to the south of Crete and modeling of its associated small tsunami

    Science.gov (United States)

    Bocchini, Gian Maria; Papadopoulos, Gerassimos A.; Novikova, Tatiana; Karastathis, Vassilis K.; Mouzakiotis, Aggelos; Voulgaris, Nikolaos

    2016-04-01

    ) and the interplate (dip ~20°) nature of the event. Okada dislocation modeling for the NNE dipping fault plane from the CMT Harvard solution was selected to run the tsunami simulations. The comparison of synthetic and observed tsunami wave heights provided an additional tool to constrain the best hypocentral solution. This research is a contribution to the EU-FP7 ITN research project ZIP (Zooming In between Plates, grant agreement no: 604713, 2013 and ASTARTE (Assessment, Strategy And Risk Reduction for Tsunamis in Europe), grant agreement no: 603839, 2013.

  13. Results of Satellite Brightness Modeling Using Kringing Optimized Interpolation

    Science.gov (United States)

    Weeden, C.; Hejduk, M.

    At the 2005 AMOS conference, Kriging Optimized Interpolation (KOI) was presented as a tool to model satellite brightness as a function of phase angle and solar declination angle (J.M Okada and M.D. Hejduk). Since November 2005, this method has been used to support the tasking algorithm for all optical sensors in the Space Surveillance Network (SSN). The satellite brightness maps generated by the KOI program are compared to each sensor's ability to detect an object as a function of the brightness of the background sky and angular rate of the object. This will determine if the sensor can technically detect an object based on an explicit calculation of the object's probability of detection. In addition, recent upgrades at Ground-Based Electro Optical Deep Space Surveillance Sites (GEODSS) sites have increased the amount and quality of brightness data collected and therefore available for analysis. This in turn has provided enough data to study the modeling process in more detail in order to obtain the most accurate brightness prediction of satellites. Analysis of two years of brightness data gathered from optical sensors and modeled via KOI solutions are outlined in this paper. By comparison, geo-stationary objects (GEO) were tracked less than non-GEO objects but had higher density tracking in phase angle due to artifices of scheduling. A statistically-significant fit to a deterministic model was possible less than half the time in both GEO and non-GEO tracks, showing that a stochastic model must often be used alone to produce brightness results, but such results are nonetheless serviceable. Within the Kriging solution, the exponential variogram model was the most frequently employed in both GEO and non-GEO tracks, indicating that monotonic brightness variation with both phase and solar declination angle is common and testifying to the suitability to the application of regionalized variable theory to this particular problem. Finally, the average nugget value, or

  14. Role of the nuclear xenobiotic receptors CAR and PXR in induction of cytochromes P450 by non-dioxinlike polychlorinated biphenyls in cultured rat hepatocytes

    Energy Technology Data Exchange (ETDEWEB)

    Gährs, Maike; Roos, Robert [University of Kaiserslautern, Food Chemistry and Toxicology, Erwin-Schroedinger-Str. 52, D-67663 Kaiserslautern (Germany); Andersson, Patrik L. [Umeå University, Department of Chemistry, Linnaeus väg 6, SE-901 87 Umeå (Sweden); Schrenk, Dieter, E-mail: schrenk@rhrk.uni-kl.de [University of Kaiserslautern, Food Chemistry and Toxicology, Erwin-Schroedinger-Str. 52, D-67663 Kaiserslautern (Germany)

    2013-10-01

    Polychlorinated biphenyls (PCBs) are among the most ubiquitously detectable ‘persistent organic pollutants’. In contrast to ‘dioxinlike’ (DL) PCBs, less is known about the molecular mode of action of the larger group of the ‘non-dioxinlike’ (NDL) PCBs. Owing to the life-long exposure of the human population, a carcinogenic, i.e., tumor-promoting potency of NDL-PCBs has to be considered in human risk assessment. A major problem in risk assessment of NDL-PCBs is dioxin-like impurities that can occur in commercially available NDL-PCB standards. In the present study, we analyzed the induction of CYP2B1 and CYP3A1 in primary rat hepatocytes using a number of highly purified NDL-PCBs with various degrees of chlorination and substitution patterns. Induction of these enzymes is mediated by the nuclear xenobiotic receptors CAR (Constitutive androstane receptor) and PXR (Pregnane X receptor). For CYP2B1 induction, concentration–response analysis revealed a very narrow window of EC{sub 50} estimates, being in the range of 1–4 μM for PCBs 28 and 52, and between 0.4 and 1 μM for PCBs 101, 138, 153 and 180. CYP3A1 induction was less sensitive to NDL-PCBs, the most pronounced induction being achieved at 100 μM with the higher chlorinated congeners. Using okadaic acid and small interfering RNAs targeting CAR and PXR, we could demonstrate that CAR plays a major role and PXR a minor role in NDL-PCB-driven induction of CYPs, both effects showing no stringent structure–activity relationship. As the only obvious relevant determinant, the degree of chlorination was found to be positively correlated with the inducing potency of the congeners. - Highlights: • We analyzed six highly purified NDL-PCBs for CYP2B1 and CYP3A1 expression. • CAR plays a major, PXR a minor role in NDL-PCB-driven induction of CYPs. • The degree of chlorination seems to be the major parameter for the inducing potency. • There exists a competition between CAR and PXR. • Activated PXR

  15. A systematic review of nonrandomized controlled trials on the curative effects of aquatic exercise

    Directory of Open Access Journals (Sweden)

    Kamioka H

    2011-03-01

    Full Text Available Hiroharu Kamioka1, Kiichiro Tsutani2, Yoshiteru Mutoh3, Hiroyasu Okuizum4, Miho Ohta5, Shuichi Handa4, Shinpei Okada6, Jun Kitayuguchi7, Masamitsu Kamada7, Nobuyoshi Shiozawa8, Sang-Jun Park4, Takuya Honda4, Shoko Moriyama41Faculty of Regional Environment Science, Tokyo University of Agriculture, Tokyo, Japan; 2Department of Drug Policy and Management, Graduate School of Pharmaceutical Sciences, 3Department of Physical and Health Education, Graduate School of Education, The University of Tokyo, Tokyo, Japan; 4Mimaki Onsen (Spa Clinic, Tomi City, Japan; 5Laboratory of Aqua, Health, and Sports Medicine, 6Physical Education and Medicine Research Foundation, Nagano, Japan; 7Physical Education and Medicine Research Center Unnan, Unnan City, Japan; 8Department of Longevity and Social Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, JapanBackground: The objectives of this review were to integrate the evidence of curative effects through aquatic exercise and assess the quality of studies based on a review of nonrandomized controlled trials (nRCTs.Methods: Study design was a systematic review of nonrandomized controlled trials. Trials were eligible if they were nonrandomized clinical trials. Studies included one treatment group in which aquatic exercise was applied. We searched the following databases from 2000 up to July 20, 2009: MEDLINE via PubMed, CINAHL, and Ichushi-Web.Results: Twenty-one trials met all inclusion criteria. Languages included were English (N = 9, Japanese (N = 11, and Korean (N = 1. Target diseases were knee and/or hip osteoarthritis, poliomyelitis, chronic kidney disease, discomforts of pregnancy, cardiovascular diseases, and rotator cuff tears. Many studies on nonspecific disease (healthy participants were included. All studies reported significant effectiveness in at least one or more outcomes. However results of evaluations with the TREND and CLEAR-NPT checklists generally

  16. New insights on Panarea volcano from terrestrial, marine and airborne data

    Science.gov (United States)

    Anzidei, Marco

    2010-05-01

    sea bottom. Finally, we provide a model constrained by GPS data and Okada formulation, which suggests that the degassing intensity and distribution are strongly influenced by geophysical-geochemical changes within the hydrothermal/geothermal system. These variations may be triggered by changes in the regional stress field as suggested by the geophysical and volcanological events which occurred in 2002 in the Southern Tyrrhenian area.

  17. BicPAMS: software for biological data analysis with pattern-based biclustering.

    Science.gov (United States)

    Henriques, Rui; Ferreira, Francisco L; Madeira, Sara C

    2017-02-02

    Biclustering has been largely applied for the unsupervised analysis of biological data, being recognised today as a key technique to discover putative modules in both expression data (subsets of genes correlated in subsets of conditions) and network data (groups of coherently interconnected biological entities). However, given its computational complexity, only recent breakthroughs on pattern-based biclustering enabled efficient searches without the restrictions that state-of-the-art biclustering algorithms place on the structure and homogeneity of biclusters. As a result, pattern-based biclustering provides the unprecedented opportunity to discover non-trivial yet meaningful biological modules with putative functions, whose coherency and tolerance to noise can be tuned and made problem-specific. To enable the effective use of pattern-based biclustering by the scientific community, we developed BicPAMS (Biclustering based on PAttern Mining Software), a software that: 1) makes available state-of-the-art pattern-based biclustering algorithms (BicPAM (Henriques and Madeira, Alg Mol Biol 9:27, 2014), BicNET (Henriques and Madeira, Alg Mol Biol 11:23, 2016), BicSPAM (Henriques and Madeira, BMC Bioinforma 15:130, 2014), BiC2PAM (Henriques and Madeira, Alg Mol Biol 11:1-30, 2016), BiP (Henriques and Madeira, IEEE/ACM Trans Comput Biol Bioinforma, 2015), DeBi (Serin and Vingron, AMB 6:1-12, 2011) and BiModule (Okada et al., IPSJ Trans Bioinf 48(SIG5):39-48, 2007)); 2) consistently integrates their dispersed contributions; 3) further explores additional accuracy and efficiency gains; and 4) makes available graphical and application programming interfaces. Results on both synthetic and real data confirm the relevance of BicPAMS for biological data analysis, highlighting its essential role for the discovery of putative modules with non-trivial yet biologically significant functions from expression and network data. BicPAMS is the first biclustering tool offering the

  18. Phosphorylation of BK channels modulates the sensitivity to hydrogen sulfide (H2S

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    Guzel F. Sitdikova

    2014-11-01

    Full Text Available Introduction: Gases, such as nitric oxide (NO, carbon monoxide (CO or hydrogen sulfide (H2S, termed gasotransmitters, play an increasingly important role in understanding of how electrical signaling of cells is modulated. H2S is well known to act on various ion channels and receptors. In a previous study we reported that H2S increased calcium-activated potassium (BK channel activity. Aims: The goal of the present study is to investigate the modulatory effect of BK channel phosphorylation on the action of H2S on the channel as well as to recalculate and determine the H2S concentrations in aqueous sodium hydrogen sulfide (NaHS solutions.Methods: Single channel recordings of GH3, GH4 and GH4 STREX cells were used to analyze channel open probability, amplitude and open dwell times. H2S was measured with ananion selective electrode. Results: The concentration of H2S produced from NaHS was recalculated taking pH, temperature salinity of the perfusate and evaporation of H2S into account. The results indicate that from a concentration of 300 µM NaHS, only11-13%, i.e. 34-41 µM is effective as H2S in solution. GH3, GH4 and GH4 STREX cells respond differently to phosphorylation. BK channel open probability (Po of all cells lines used was increased by H2S in ATP containing solutions. PKA prevented the action of H2S on channel Po in GH4 and GH4 STREX, but not in GH3 cells. H2S, high significantly increased Po of all PKG pretreated cells. In the presence of PKC, which lowers channel activity, H2S increased channel Po of GH4 and GH4 STREX, but not those of GH3 cells. H2S increased open dwell times of GH3 cells in the absence of ATP significantly. A significant increase of dwell times with H2S was also observed in the presence of okadaic acid.Conclusions: Our results suggest that phosphorylation by PKG primes the channels for H2S activation and indicate that channel phosphorylation plays an important role in the response to H2S.

  19. Avarol derivatives as competitive AChE inhibitors, non hepatotoxic and neuroprotective agents for Alzheimer's disease.

    Science.gov (United States)

    Tommonaro, Giuseppina; García-Font, Nuria; Vitale, Rosa Maria; Pejin, Boris; Iodice, Carmine; Cañadas, Sixta; Marco-Contelles, José; Oset-Gasque, María Jesús

    2016-10-21

    Avarol is a marine sesquiterpenoid hydroquinone, previously isolated from the marine sponge Dysidea avara Schmidt (Dictyoceratida), with antiinflammatory, antitumor, antioxidant, antiplatelet, anti-HIV, and antipsoriatic effects. Recent findings indicate that some thio-avarol derivatives exhibit acetylcholinesterase (AChE) inhibitory activity. The multiple pharmacological properties of avarol, thio-avarol and/or their derivatives prompted us to continue the in vitro screening, focusing on their AChE inhibitory and neuroprotective effects. Due to the complex nature of Alzheimer's disease (AD), there is a renewed search for new, non hepatotoxic anticholinesterasic compounds. This paper describes the synthesis and in vitro biological evaluation of avarol-3'-thiosalicylate (TAVA) and thiosalycil-prenyl-hydroquinones (TPHs), as non hepatotoxic anticholinesterasic agents, showing a good neuroprotective effect on the decreased viability of SHSY5Y human neuroblastoma cells induced by oligomycin A/rotenone and okadaic acid. A molecular modeling study was also undertaken on the most promising molecules within the series to elucidate their AChE binding modes and in particular the role played by the carboxylate group in enzyme inhibition. Among them, TPH4, bearing a geranylgeraniol substituent, is the most significant Electrophorus electricus AChE (EeAChE) inhibitor (IC50 = 6.77 ± 0.24 μM), also endowed with a moderate serum horse butyrylcholinesterase (eqBuChE) inhibitory activity, being also the least hepatotoxic and the best neuroprotective compound of the series. Thus, TPHs represents a new family of synthetic compounds, chemically related to the natural compound avarol, which has been discovered for the potential treatment of AD. Findings prove the relevance of TPHs as a new possible generation of competitive AChE inhibitors pointing out the importance of the salycilic substituents on the hydroquinone ring. Since these compounds do not belong to the class of

  20. LRRK2 Kinase Activity and Biology are Not Uniformly Predicted by its Autophosphorylation and Cellular Phosphorylation Site Status

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    April eReynolds

    2014-06-01

    Full Text Available Missense mutations in the Leucine Rich Repeat protein Kinase 2 (LRRK2 gene are the most common genetic predisposition to develop Parkinson’s disease (PD LRRK2 is a large multi-domain phosphoprotein with a GTPase domain and a serine/threonine protein kinase domain whose activity is implicated in neuronal toxicity; however the precise mechanism is unknown. LRRK2 autophosphorylates on several serine/threonine residues across the enzyme and is found constitutively phosphorylated on Ser910, Ser935, Ser955 and Ser973, which are proposed to be regulated by upstream kinases. Here we investigate the phosphoregulation at these sites by analyzing the effects of disease-associated mutations Arg1441Cys, Arg1441Gly, Ala1442Pro, Tyr1699Cys, Ile2012Thr, Gly2019Ser, and Ile2020Thr. We also studied alanine substitutions of phosphosite serines 910, 935, 955 and 973 and specific LRRK2 inhibition on autophosphorylation of LRRK2 Ser1292, Thr1491, Thr2483 and phosphorylation at the cellular sites. We found that mutants in the Roc-COR domains, including Arg1441Cys, Arg1441His, Ala1442Pro and Tyr1699Cys, can positively enhance LRRK2 kinase activity while concomitantly inducing the dephosphorylation of the cellular sites. Mutation of the cellular sites individually did not affect LRRK2 intrinsic kinase activity; however, Ser910/935/955/973Ala mutations trended toward increased kinase activity of LRRK2. Increased cAMP levels did not lead to increased LRRK2 cellular site phosphorylation, 14-3-3 binding or kinase activity. In cells, inhibition of LRRK2 kinase activity leads to dephosphorylation of Ser1292 by Calyculin A and okadaic acid sensitive phosphatases, while the cellular sites are dephosphorylated by Calyculin A sensitive phosphatases. These findings indicate that comparative analysis of both Ser1292 and Ser910/935/955/973 phosphorylation sites will provide important and distinct measures of LRRK2 kinase and biological activity in vitro and in vivo.

  1. Protein phosphatase 2A mediates dormancy of glioblastoma multiforme-derived tumor stem-like cells during hypoxia.

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    Christoph P Hofstetter

    Full Text Available PURPOSE: The hypoxic microenvironment of glioblastoma multiforme (GBM is thought to increase resistance to cancer therapies. Recent evidence suggests that hypoxia induces protein phosphatase 2A (PP2A, a regulator of cell cycle and cell death. The effects of PP2A on GBM tumor cell proliferation and survival during hypoxic conditions have not been studied. EXPERIMENTAL DESIGN: Expression of PP2A subunits and HIF-α proteins was measured in 65 high-grade astrocytoma and 18 non-neoplastic surgical brain specimens by western blotting. PP2A activity was measured by an immunoprecipitation assay. For in vitro experiments, GBM-derived tumor stem cell-like cells (TSCs were exposed to severe hypoxia produced by either CoCl₂ or 1% O₂. PP2A activity was inhibited either by okadaic acid or by shRNA depletion of the PP2A C subunit. Effects of PP2A activity on cell cycle progression and cell survival during hypoxic conditions were assessed using flow cytometry. RESULTS: In our patient cohort, PP2A activity was positively correlated with HIF-1∝ protein expression (P = 0.002. Patients with PP2A activity levels above 160 pMP had significantly worse survival compared to patients with levels below this threshold (P = 0.002. PP2A activity was an independent predictor of survival on multivariable analysis (P = 0.009. In our in vitro experiments, we confirmed that severe hypoxia induces PP2A activity in TSCs 6 hours after onset of exposure. PP2A activity mediated G1/S phase growth inhibition and reduced cellular ATP consumption in hypoxic TSCs. Conversely, inhibition of PP2A activity led to increased cell proliferation, exhaustion of intracellular ATP, and accelerated P53-independent cell death of hypoxic TSCs. CONCLUSIONS: Our results suggest that PP2A activity predicts poor survival in GBM. PP2A appears to reduce the metabolic demand of hypoxic TSCs and enhances tumor cell survival. Modulation of PP2A may be a potential target for cancer therapy.

  2. A systematic review of randomized controlled trials on curative and health enhancement effects of forest therapy

    Directory of Open Access Journals (Sweden)

    Kamioka H

    2012-07-01

    Full Text Available Hiroharu Kamioka,1 Kiichiro Tsutani,2 Yoshiteru Mutoh,3 Takuya Honda,4 Nobuyoshi Shiozawa,5 Shinpei Okada,6 Sang-Jun Park,6 Jun Kitayuguchi,7 Masamitsu Kamada,8 Hiroyasu Okuizumi,9 Shuichi Handa91Faculty of Regional Environment Science, Tokyo University of Agriculture, Tokyo, 2Department of Drug Policy and Management, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, 3Todai Policy Alternatives Research Institute, The University of Tokyo, Tokyo, 4Japanese Society for the Promotion of Science, Tokyo, 5Food Labeling Division, Consumer Affairs Agency, Cabinet Office, Government of Japan, Tokyo, 6Physical Education and Medicine Research Foundation, Nagano, 7Physical Education and Medicine Research Center Unnan, Shimane, 8Department of Environmental and Preventive Medicine, Shimane University School of Medicine, Shimane, 9Mimaki Onsen (Spa Clinic, Tomi City, Nagano, JapanObjective: To summarize the evidence for curative and health enhancement effects through forest therapy and to assess the quality of studies based on a review of randomized controlled trials (RCTs.Study design: A systematic review based on RCTs.Methods: Studies were eligible if they were RCTs. Studies included one treatment group in which forest therapy was applied. The following databases – from 1990 to November 9, 2010 – were searched: MEDLINE via PubMed, CINAHL, Web of Science, and Ichushi-Web. All Cochrane databases and Campbell Systematic Reviews were also searched up to November 9, 2010.Results: Two trials met all inclusion criteria. No specific diseases were evaluated, and both studies reported significant effectiveness in one or more outcomes for health enhancement. However, the results of evaluations with the CONSORT (Consolidated Standards of Reporting Trials 2010 and CLEAR NPT (A Checklist to Evaluate a Report of a Nonpharmacological Trial checklists generally showed a remarkable lack of description in the studies. Furthermore, there was a

  3. Transcriptional regulation, stabilization, and subcellular redistribution of multidrug resistance-associated protein 1 (MRP1) by glycogen synthase kinase 3αβ: novel insights on modes of cadmium-induced cell death stimulated by MRP1.

    Science.gov (United States)

    Kim, Hak-Ryul; Lee, Kang-Yo; Lee, Kang-Yoo; Ahn, Sang-Gun; Lee, Byung-Hoon; Jung, Ki-Tae; Yoon, Jung-Hoon; Yoon, Hyo-Eun; Oh, Seon-Hee

    2015-08-01

    Cadmium (Cd) resistance is associated with the suppression of autophagy in H460 lung cancer cells, which is regulated by phospho(p)serine-glycogen synthase kinase (GSK) 3αβ. However, the involvement of multidrug resistance (MDR) in this signaling pathway and its underlying mechanisms remain to be elucidated. In this study, we used Cd-resistant cells (RH460), developed from H460 lung cancer cells, to demonstrate that the induction of MDR-associated protein (MRP1) in response to Cd is enhanced in H460 cells compared to RH460. Treating RH460 cells with Cd induced large cytoplasmic vacuoles, which was inhibited by the autophagy inhibitor 3-methyladenine. MRP1 was detected in the nuclear-rich membrane fractions and redistributed from the perinuclear to the cytoplasmic compartment following exposure to Cd. Cd-induced MRP1, p-Ser/p-Tyr GSK3αβ, and LC3-II were all suppressed by the GSK3 inhibitor SB216763, but increased by lithium. Furthermore, MRP1 was upregulated by the Ser/Thr phosphatase inhibitor okadaic acid and downregulated by the tyrosine phosphatase inhibitor vanadate, suggesting that MRP1 protein was stabilized by p-Ser GSK3αβ. In addition, co-immunoprecipitation and co-localization analyzes revealed a physical interaction between MRP1 and p-Ser GSK3αβ. Genetic knockdown of GSK3β decreased Cd-induced MRP1 mRNA and protein levels, whereas its overexpression upregulated MRP1 protein expression. MRP1 also co-localized with lysosomal membrane protein-2, which may cause lysosomal membrane permeabilization and the subsequent release of cathepsins into the cytosol. In mice chronically injected with Cd, MRP1 localized to the perinuclear region of bronchial and alveolar epithelial cells. Collectively, these data suggest that Cd toxicity is regulated by the transcriptional regulation, stabilization, and subcellular redistribution of MRP1 via the posttranslational modification of GSK3αβ. Therefore, the serine phosphorylation of GSK3αβ plays a critical role in

  4. Sigma-1 receptor concentration in plasma of patients with late-life depression: a preliminary study

    Directory of Open Access Journals (Sweden)

    Shimizu H

    2013-12-01

    Full Text Available Hideyuki Shimizu,1 Minoru Takebayashi,2 Masayuki Tani,1 Hiroaki Tanaka,1 Bun Yamagata,1 Kenzo Kurosawa,1 Hiroki Yamada,1 Mitsugu Hachisu,3 Kazue Hisaoka-Nakashima,2 Mami Okada-Tsuchioka,2 Masaru Mimura,4 Akira Iwanami11Department of Neuropsychiatry, Showa University School of Medicine, Tokyo, Japan; 2Department of Psychiatry and Institute for Clinical Research, National Hospital Organization Kure Medical Center, Kure, Japan; 3Department of Clinical Psychopharmacy, Pharmacy School, Showa University, Tokyo, Japan; 4Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, JapanBackground: Recently, the sigma-1 receptor has been shown to play a significant role in the neural transmission of mood by regulating N-methyl-D-aspartate receptors. Additionally, the sigma-1 receptor has been reported to influence cognitive functions including learning and memory. In this study, we measured plasma sigma-1 receptor concentrations before and after antidepressant treatment in patients with late-life major depressive disorder (MDD and explored whether changes in depressive status are related to sigma-1 receptor concentrations.Methods: The study participants were 12 subjects with late-life MDD diagnosed according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. All of the participants were over 60 years old. Immediately prior to and 8 weeks after the start of treatment, sigma-1 receptor concentration and mental status, including depressive symptoms (Hamilton Depression Rating Scale; HAM-D, were measured. Treatment for depression was performed according to a developed algorithm based on the choice of treatments. We examined the association between changes in sigma-1 receptor concentration and HAM-D scores during antidepressant treatment. For the measurement of plasma sigma-1 receptor concentration, blood plasma samples were separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis. Western

  5. The cyclooxygenase-2 inhibitor celecoxib induces apoptosis by blocking Akt activation in human prostate cancer cells independently of Bcl-2.

    Science.gov (United States)

    Hsu, A L; Ching, T T; Wang, D S; Song, X; Rangnekar, V M; Chen, C S

    2000-04-14

    phosphoinositide 3-kinase activity in vivo and okadaic acid, a protein phosphatase 2A inhibitor, cannot rescue the inhibition. In summary, our data demonstrate that inhibition of Akt activation may play a crucial role in the induction of apoptosis by celecoxib.

  6. Numerical Simulation of Fault Interaction in a Trans-Tensional Setting, the La Paz Los Cabos Region, Baja California, Mexico.

    Science.gov (United States)

    Zielke, O.; Arrowsmith, R. J.

    2006-12-01

    A number of medium to large normal faulting earthquakes occurred in the La Paz-Los Cabos region, at the tip of Baja California, within the last four decades. They (along with the tectonic geomorphology of the fault zones on the Peninsula) demonstrate that the existing structures in the area are active and capable of hazardous earthquakes. The goal of this study is to understand how the individual active faults in this region affect the behavior of the fault system as a whole. What role does fault interaction (i.e., stress transfer) and earthquake triggering play in the La Paz-Los Cabos region? Do we know all the significant, active and therefore hazardous structures that are part of the fault system? Are these structures capable of releasing the tectonically accumulated strain? What role does that fault system play in the regional, trans-tensional setting? To approach these questions we utilize a numerical model, based on derivations by Okada (1992), with which we compute the strain distribution and Coulomb failure stress for a given (frictionless) displacement along a rectangular fault patch and its interactions with other faults of the fault array. Beginning with simple geometric models of the fault system in the La Paz-Los Cabos region, we investigate under what conditions individual earthquakes may have triggered subsequent events. We focused on the M =5.6 event on April 4th 1969 that may have had an effect on the timing of the M=6.2 event on June 30th 1995. The proximity of these two earthquakes (epicenters only 60km apart) supports the idea that stress transfer caused by the 1969 event may have altered the seismic cycle of the fault activated in 1995. Because fault geometry and slip distribution during these two events are not well known, we explore the parameter space to learn under what conditions the 1969 event may have triggered the 1995 event. We apply the empirical relations among magnitude, fault geometry, and displacement, derived by Wells

  7. Slip Updip of Tremor during the 2012 Cascadia ETS Event

    Science.gov (United States)

    Hall, K.; Houston, H.

    2014-12-01

    The interplay between tremor and slow slip during ETS has implications for the slip budget of the Cascadia subduction zone. In particular, it can constrain the downdip edge of the locked zone, which informs the hazard assessments for major cities including Seattle, Tacoma, and Vancouver. As shown by Houston (AGU abstract, 2012), slip inferred from GPS extended updip of the seismically-detected tremor in the 2010 M6.8 ETS event. Following the methods used on the 2010 ETS event, we used the PANGA GPS to measure the displacement vectors for 71 stations to analyze a large ETS event in 2012 that extended from Vancouver Island to Southern Washington. We implemented Principal Component Analysis to automatically select the direction and magnitude of the maximum displacement vector. We then inverted these GPS displacements for slip, using the Okada formulation of buried rectangular faults in a halfspace with a grid of 8 by 8 km subfaults based on the McCrory slab model. We performed inversions with either 0th or 2nd order Tikhonov regularization and found that over the 6 weeks of propagation, the 2012 ETS event released moment corresponding to M6.7, in three high-slip regions. We compared two different inversions, one where slip was allowed on a broad regional grid and a tremor-restricted inversion (TRI) where slip was restricted to grid locations where tremor had been detected in the 2012 ETS. We found that the TRI forced the slip to the updip edge of the grid where it reached above 10 cm, which is physically implausible given that this exceeds the slip that can accumulate in an inter-ETS time period. Additionally, the regional grid inversion indicates that 1 to 2 cm of slip occurred 10's of km updip of the western edge of tremor. This further supports the inference from the 2010 event that in northern Washington, the slow slip during an ETS event extends many kilometers updip of the western edge of tremor.

  8. Spatial and Temporal Comparisons of Tremor and Slow Slip in Cascadia

    Science.gov (United States)

    Hall, K.; Houston, H.; Schmidt, D. A.

    2015-12-01

    Tremor is often thought to be a proxy for slip during ETS events and has been shown to have a relatively abrupt updip boundary, implying an abrupt updip limit of slip. However, as shown by Houston (AGU abstract, 2012) and Hall and Houston (AGU abstract, 2014), slip inferred from GPS extended updip of the seismically-detected tremor in the 2010 M6.8 and 2012 M6.7 ETS events. If slip extending updip of tremor is a persistent phenomena, tremor cannot be directly used as a proxy for slip. Following the methods used on the 2010 and 2012 ETS event, we found that the August 2009 ETS around Portland, OR also showed slip updip of tremor. Principal Component Analysis was implemented to automatically select the direction and magnitude of the maximum displacement vector. Our Green's functions use the Okada formulation of buried rectangular faults in a halfspace for a grid of 8x8 km subfaults based on the McCrory slab model. We then performed static inversions with 2nd order Tikhonov regularization to find slip on the fault surface. We also compared two different inversions for 2009, one where slip was allowed on a broad regional grid and a tremor-restricted inversion (TRI) where slip was restricted to subfaults in which tremor occurred. We found the 2009 ETS event released the equivalent of a M6.8 in slip. We also found that, as in the previous ETSs, the TRI forced up to 10 cm of slip to the updip edge of the grid, which is exceeds the amount of plate convergence expected in the inter-ETS periods and is therefore physically unsustainable over several ETS events. The excess slip along the updip edge in the TRI models also suggests that the geodetic data prefer slip with a larger footprint than the spatial pattern of tremor, and supports our conclusion that tremor does not represent all of the slip during an ETS event. We see consistent and clear spatial relationship between tremor and slip with some slip occurring updip of tremor. Our static inversions show where slip is

  9. Tsunami Hazard in the Algerian Coastline

    Science.gov (United States)

    Amir, L. A.

    2008-05-01

    The Algerian coastline is located at the border between the African and the Eurasian tectonic plates. The collision between these two plates is approximately 4 to 7 mm/yr. The Alps and the tellian Atlas result from this convergence. Historical and present day data show the occurrence of earthquakes with magnitude up to 7 degrees on Richter scale in the northern part of the country. Cities were destroyed and the number of victims reached millions of people. Recently, small seismic waves generated by a destructive earthquake (Epicenter: 36.90N, 3.71E; Mw=6.8; Algeria, 2003, NEIC) were recorded in the French and Spanish coasts. This event raised again the issue of tsunami hazard in western Mediterranean region. For the Algerian study case, the assessment of seismic and tsunami hazard is a matter of great interest because of fast urban development of cities like Algiers. This study aims to provide scientific arguments to help in the elaboration of the Mediterranean tsunami alert program. This is a real complex issue because (1) the western part of the sea is narrow, (2) constructions on the Algerian coastline do not respect safety standards and (3) the seismic hazard is important. The present work is based on a numerical modeling approach. Firstly, a database is created to gather and list information related to seismology, tectonic, abnormal sea level's variations recorded/observed, submarine and coastal topographic data for the western part of the Mediterranean margin. This database helped to propose series of scenario that could trigger tsunami in the Mediterranean sea. Seismic moment, rake and focal depth are the major parameters that constrain the modeling input seismic data. Then, the undersea earthquakes modeling and the seabed deformations are computed with a program adapted from the rngchn code based on Okada's analytic equations. The last task of this work consisted to calculate the initial water surface displacement and simulate the triggered tsunami

  10. Development and application of the PCC biodosimetry method in emergency preparedness

    Energy Technology Data Exchange (ETDEWEB)

    Stricklin, D. (Swedish Defence Research Agency, FOI (Sweden)); Lindholm, C. (Finnish Radiation and Nuclear Safety Authority, STUK (Finland)); Jaworska, A. (Norwegian Radiation Protection Authority, NRPA (Norway))

    2008-07-15

    A method for biological assessment of radiation dose for specific application in emergency preparedness was developed. Premature chromosome condensation (PCC) was investigated to provide a potentially faster means of analysis and the ability to assess higher doses than with the dicentric assay which is routinely applied in biodosimetry today. A review of existing methods was made, followed by experiments determine optimal assay conditions, and evaluations to determination of optimal conditions and the most appropriate endpoints for analyses. Twelve different experimental conditions were examined with four different evaluation approaches. Aspects during optimization such as practicality, speed, and reliability were considered. The conclusion from these studies was a PCC protocol utilizing okadaic acid for induction of PCC cells in stimulated lymphocytes but without the use of colcemid for metaphase arrest with the subsequent evaluation of ring chromosomes. Well-defined criteria were established for evaluation of PCC cells and ring chromosome aberrations. An inter-calibration was made by comparing assessment of ring chromosomes between all three laboratories. Agreement was made to count only rings with observable open spaces or large, obvious rings without open spaces. Finally a dose response curve for the PCC method was prepared and a comparison of the PCC method to the traditional dicentric assay in triage mode was made. The triage method requires a minimal number of evaluations so that categorization of high, medium and low doses may be made in an emergency situation where large numbers of people should be evaluated. The comparison of the PCC method with the dicentric assay triage method indicated that the PCC assay performed superior to the dicentric assay for evaluation of samples at higher doses, however, the dicentric assay appeared to provide more accurate dose assessment at lower doses. This project suggests a PCC assay method for biological dose estimates

  11. Analysis of the displacement of geodetic stations during the Emilia seismic sequence of May 2012

    Directory of Open Access Journals (Sweden)

    Alessandro Caporali

    2012-10-01

    study, we present more detailed estimates of the coseismic offsets at several other stations in the area, including a kinematic solution at 30 s temporal resolution. The coseismic displacements are inverted using the Okada [1985] model and a preliminary model of the two faults is obtained for each of the two main events, taking into account the available synthetic aperture radar (SAR data. […

  12. 液相色谱-串联质谱法检测9种腹泻性贝毒毒素%Determination of 9 kinds of diarrhetic shellfish poisoning toxins by liquid chromatography-tandem mass spectrometry

    Institute of Scientific and Technical Information of China (English)

    吴振兴; 静平; 曹文卿; 鲍蕾; 梁成珠; 宫小明

    2015-01-01

    目的:建立腹泻性贝毒毒素9种代表性化合物:大田软海绵酸、鳍藻毒素、蛤毒素2、扇贝毒素及其衍生物、环亚胺米氏裸甲藻毒素、螺环内酯毒素1和原多甲藻酸的高效液相色谱-电喷雾串联质谱(HPLC-ESI-MS/MS)检测方法。方法以80%甲醇水溶液对贝类组织中的毒素进行提取,再以亲水亲脂平衡柱(HLB)对提取液进行净化,最后以高效液相色谱-电喷雾串联质谱测定。结果 DSP毒素9种代表性化合物在各自浓度范围内线性良好,回收率为68.9%~94.2%,精密度为3.5%~9.5%。结论该方法具有灵敏度高、重现性好、操作简便、准确可靠等特点,适用于贝类中腹泻性贝毒毒素的测定。%Objective To establish a high performance liquid chromatography (HPLC)-electrospray ionization mass spectrometry method for determination of 9 kinds of representative diarrhetic shellfish poisoning (DSP) toxins including okadaic acid(OA), dinophysistoxin1, 2(DTX1, DTX2), pectenotoxin2(PTX2), yessotoxin(YTX), homo-yessotoxin(hYTX), gymnodimine(GYM), spirolide1(SPX1) and azaspiracid1(AZA1) in shellfish. Methods The toxins were extracted with 80%methanol aqueous solution from the shellfish, then cleaned up by hydrophile-lipophile balance columns, at last, the extractive was determined by a reversed phase HPLC gradient program coupled with electrospray ionization mass spectrometry. Results Nine representative diarrhetic shellfish poisoning toxins had a good linear relationship in respective concentration range, the average recoveries were ranged from 68.9%~94.2%, and the precision was in ranged from 3.5%~9.5%. Conclusion The developed method is simple and accurate, which can be applied for determination of DSP toxins in shellfish.

  13. Crustal deformation of Miyakejima volcano, Japan since the eruption of 2000 using dense GPS campaign observation

    Science.gov (United States)

    Fukui, M.; Matsushima, T.; Oikawa, J.; Watanabe, A.; Okuda, T.; Ozawa, T.; Kohno, Y.; Miyagi, Y.

    2013-12-01

    Miyakejima is an active volcanic Island located about 175 km south of Tokyo, Japan. Miyakejima volcano erupted approximately every 20 years in the past 100 years. The latest eruptive activities since 2000 was different from those of the last 100 years, in that the activities included a caldera formation for the first time in 2500 years and gigantic volcanic gas emission that forced islander to evacuate over four and half years. In 2000, a dense GPS observation campaign had detected the magma intrusion in detail (e.g., Irwan et al., 2003; Murase et al., 2006). However, this campaign observation ceased from 2002 to 2010 because a large amount of volcanic gas prevented from entering to the island. Since 2011, we restarted the campaign observation by the dense GPS network, and examined the ongoing magma accumulation process beneath Miyakejima volcano to get insights about the future activity. In this analysis, we combined the data of our campaign observations, the data of the University Union in 2000, and the GEONET data. The observation data were analyzed by RTK-LIB (Takasu et al., 2007) using GPS precise ephemeris from IGS. We estimated the locations and volumes of the pressure sources beneth Miyakejima using an elevation-modified Mogi model (Fukui et al., 2003) and open crack model (Okada, 1992) during the two periods (2000 ~ 2012 and 2011 ~ 2012). We used the software of Magnetic and Geodetic data Computer Analysis Program for Volcano (MaGCAP-V) (Fukui et al., 2010), and estimated the source parameters by trial and error. During 2000 and 2012, a contracting spherical source and contracting dyke were estimated beneath the caldera and at the southwestern part of the island, respectively. In contrast, during 2011 and 2012, an spherical inflation source was estimated a few km beneath the caldera. This result suggest that Miyakejima is now storing new magma for the next eruption. Geospatial Information Authority of Japan (GSI) (2011) suggested that the inflation started

  14. The Mw 6.0 2016 Amatrice (Italy) Earthquake: Source Geometry Inferred from DInSAR Measurements and Geological Data.

    Science.gov (United States)

    Casu, F.; Lavecchia, G.; Castaldo, R.; De Nardis, R.; De Novellis, V.; Ferrarini, F.; Pepe, S.; Brozzetti, F.; Solaro, G.; Cirillo, D.; Bonano, M.; Boncio, P.; de Luca, C.; Lanari, R.; Manunta, M.; Manzo, M.; Pepe, A.; Zinno, I.; Tizzani, P.

    2016-12-01

    On 24 August 2016, at 01:36 UTÇ the intra-Apennine extensional fault system of Central Italy released a destructive earthquake (MW 6.0). It produced widespread damage and fatalities, killing about 300 people and severely destroying the town of Amatrice and surrounding villages. After few hours, the Amatrice earthquake was followed by a significant aftershock (MW 5.5), which nucleated 15 km NW-ward. The epicentral area of the seismic sequence extends in the NNW-SSE direction, for a length of about 25-30 km. It is located at the hanging-wall of the WSW-dipping Vettore-Gorzano active extensional fault system. During the days following the main shock, a significant number of Synthetic Aperture Radar (SAR) data have been acquired from different passes and angles by the L-band ALOS-2, C-band Sentinel-1 and X-band COSMO-SkyMed satellites. This allowed us to map in a very short time the co-seismic ground displacements through the Differential SAR Interferometry (DInSAR) technique, and also to evaluate their Vertical and East-West components with high details. The generated interferometric pattern is characterized by a double-eyed co-seismic shape that spans 20 km along the NNW-SSE direction and that well coincides with the epicentral areas. We modeled the seismic source that well fit the Mw 6.2 event. In particular, for this analysis, we separately applied an analytical Okada approach as well as a 3D Finite Element (FE) numerical modeling, the latter jointly exploiting DInSAR measurements and structural-geological data. The model obtained via the FE approach suggests that the Amatrice 2016 earthquake nucleated at 8 km deep along the intersection line between the Vettoretto-Redentore and the Northern Gorzano faults, and instantly geminated in two rupture patches that radiated with an approximate bilateral symmetry on the two fault planes. The two rupture patches covered differently shaped slip area, with aspect ratio that well recalls the shape of the interferometric lobes

  15. Finite Element analysis of source geometry and slip distribution of the 2016 Amatrice Mw 6.2 earthquake (Central Italy) through the integration of geological and satellite data

    Science.gov (United States)

    Tizzani, Pietro; Castaldo, Raffaele; De Novellis, Vincenzo; Pepe, Susi; Solaro, Giuseppe; Bonano, Manuela; De Luca, Claudio; Casu, Francesco; Manunta, Michele; Lanari, Riccardo; Manzo, Mariarosaria; Pepe, Antonio; Zinno, Ivana; Lavecchia, Giusy; de Nardis, Rita; Ferrarini, Federica; Brozzetti, Francesco; Cirillo, Daniele; Boncio, Paolo

    2017-04-01

    On 24 August 2016 (01:36 UTC) the intra-Apennine extensional fault system of Central Italy released a ML 6.0 destructive earthquake between the towns of Norcia and Amatrice. The main shock produced widespread damages and fatalities, devastating several localities and killing about 300 people. The main event was followed by a significant aftershock (ML 5.4), located 15 km to the NW. After one week, the epicentral area reached a length of about 30 km, in the NNW-SSE direction, largely developing at the hanging-wall of the WSW-dipping active extensional Vettore and Gorzano faults. The reconstructed 3D fault model consists in two major interconnected fault segments, Vettore and Gorzano, which are individual at depth shallower than about 7-8 km and converge into a unified surface at higher depths; the Vettore-Gorzano unified surface has a length of 65 km, dips WSW-ward with an angle of about 45-50° and reaches a depth of 11 km. By inverting the generated interferograms, following a classical Okada analytical approach, the best modelling results account for two sources related to main shock and more energetic aftershock. The time interval between the ascending and descending (31 August 2016) does not discriminate the effects derived from the main 24 August event and by its aftershock, but the low magnitude of the second event can only very marginally contribute to the overall deformation pattern. Through Finite Element modelling that jointly exploits DInSAR deformation measurements and structural-geological data, we reconstruct the 3D source of the Accumoli 2016 normal fault earthquake which fit better a moment Mw 6.2. As results of our modelling, we retrieve (i) the active seismogenic structures responsible for the observed ground deformation, (ii) the spatial distribution of the local stress field in term of volumetric stress and strain. The inversion shows that the co-seismic displacement area was partitioned on two distinct en echelon fault planes, which at the main

  16. Reexamination of the Matuyama-Brunhes Polarity Transition Near Bishop, California

    Science.gov (United States)

    Liddicoat, J.; Kravchinsky, V.

    2012-04-01

    There is half a century of recorded knowledge of the behaviour of the palaeomagnetic field during a polarity transition beginning with Van Zijl et al.'s 1962 report of a transition in Stormberg lavas, and for the Matuyama-Brunhes polarity transition (MBPT) about 0.78 m.y. ago it has been investigated in marine, lacustrine, and volcanic rocks. Among the earliest of the MBPT investigations was a study of bathyal siltstone on the Boso Peninsula in Japan (Niitsuma, 1971; Okada and Niitsuma, 1989). That investigation was preceded by a report that the relative intensity of the palaeomagnetic field as recorded in a marine core is reduced for a longer period of time than is required for the palaeomagnetic directions to reverse polarity (Ninkovich et al., 1966), a discovery that was summarized for other reversals in cored marine sediment (Opdyke, 1973). Nearly 40 years ago, Hillhouse and Cox (1976) followed the palaeomagnetic directions and relative field intensity during the MBPT using exposed Pleistocene Lake Tecopa sediments in southeastern California. They reported a generally smooth path of the Virtual Geomagnetic Poles (VGPs) as the field changed from reverse to normal that does not coincide with the VGP path for the MBPT in Japan, concluding that the transitional field is predominantly the non-dipole field. At Lake Tecopa, as in the marine record, the reduction in field strength occurred sooner and lasted longer by a factor of at least two the time required for the palaeomagnetic directions to reverse polarity, which was confirmed by Valet et al. (1988) at the same locality. Soon thereafter, the MBPT was studied in Pleistocene lacustrine sediments exposed beneath the Bishop Tuff (Dalrymple et al., 1965) near Bishop, California (37.4˚ N, 241.5˚ E) (Liddicoat, 1982; 1993). The data we report are for directional and normalized relative intensity measurements of additional samples from each horizon at the Bishop locality that indicate the time spanned by the reduction

  17. Lipid rafts regulate PCB153-induced disruption of occludin and brain endothelial barrier function through protein phosphatase 2A and matrix metalloproteinase-2

    Energy Technology Data Exchange (ETDEWEB)

    Eum, Sung Yong, E-mail: seum@miami.edu; Jaraki, Dima; András, Ibolya E.; Toborek, Michal

    2015-09-15

    Occludin is an essential integral transmembrane protein regulating tight junction (TJ) integrity in brain endothelial cells. Phosphorylation of occludin is associated with its localization to TJ sites and incorporation into intact TJ assembly. The present study is focused on the role of lipid rafts in polychlorinated biphenyl (PCB)-induced disruption of occludin and endothelial barrier function. Exposure of human brain endothelial cells to 2,2′,4,4′,5,5′-hexachlorobiphenyl (PCB153) induced dephosphorylation of threonine residues of occludin and displacement of occludin from detergent-resistant membrane (DRM)/lipid raft fractions within 1 h. Moreover, lipid rafts modulated the reduction of occludin level through activation of matrix metalloproteinase 2 (MMP-2) after 24 h PCB153 treatment. Inhibition of protein phosphatase 2A (PP2A) activity by okadaic acid or fostriecin markedly protected against PCB153-induced displacement of occludin and increased permeability of endothelial cells. The implication of lipid rafts and PP2A signaling in these processes was further defined by co-immunoprecipitation of occludin with PP2A and caveolin-1, a marker protein of lipid rafts. Indeed, a significant MMP-2 activity was observed in lipid rafts and was increased by exposure to PCB153. The pretreatment of MMP-2 inhibitors protected against PCB153-induced loss of occludin and disruption of lipid raft structure prevented the increase of endothelial permeability. Overall, these results indicate that lipid raft-associated processes, such as PP2A and MMP-2 activation, participate in PCB153-induced disruption of occludin function in brain endothelial barrier. This study contributes to a better understanding of the mechanisms leading to brain endothelial barrier dysfunction in response to exposure to environmental pollutants, such as ortho-substituted PCBs. - Highlights: • PCB153 disturbed human brain endothelial barrier through disruption of occludin. • Lipid raft-associated PP

  18. The 2016 central Italy earthquake sequence: surface effects, fault model and triggering scenarios

    Science.gov (United States)

    Chatzipetros, Alexandros; Pavlides, Spyros; Papathanassiou, George; Sboras, Sotiris; Valkaniotis, Sotiris; Georgiadis, George

    2017-04-01

    The results of fieldwork performed during the 2016 earthquake sequence around the karstic basins of Norcia and La Piana di Castelluccio, at an altitude of 1400 m, on the Monte Vettore (altitude 2476 m) and Vettoretto, as well as the three mapped seismogenic faults, striking NNW-SSW, are presented in this paper. Surface co-seismic ruptures were observed in the Vettore and Vettoretto segment of the fault for several kilometres ( 7 km) in the August earthquakes at high altitudes, and were re-activated and expanded northwards during the October earthquakes. Coseismic ruptures and the neotectonic Mt. Vettore fault zone were modelled in detail using images acquired from specifically planned UAV (drone) flights. Ruptures, typically with displacement of up to 20 cm, were observed after the August event both in the scree and weathered mantle (elluvium), as well as the bedrock, consisting mainly of fragmented carbonate rocks with small tectonic surfaces. These fractures expanded and new ones formed during the October events, typically of displacements of up to 50 cm, although locally higher displacements of up to almost 2 m were observed. Hundreds of rock falls and landslides were mapped through satellite imagery, using pre- and post- earthquake Sentinel 2A images. Several of them were also verified in the field. Based on field mapping results and seismological information, the causative faults were modelled. The model consists of five seismogenic sources, each one associated with a strong event in the sequence. The visualisation of the seismogenic sources follows INGV's DISS standards for the Individual Seismogenic Sources (ISS) layer, while strike, dip and rake of the seismic sources are obtained from selected focal mechanisms. Based on this model, the ground deformation pattern was inferred, using Okada's dislocation solution formulae, which shows that the maximum calculated vertical displacement is 0.53 m. This is in good agreement with the statistical analysis of the

  19. Study of the mechanisms involved in the vasorelaxation induced by (−)-epigallocatechin-3-gallate in rat aorta

    Science.gov (United States)

    Álvarez, Ezequiel; Campos-Toimil, Manuel; Justiniano-Basaran, Hélène; Lugnier, Claire; Orallo, Francisco

    2005-01-01

    This study investigated several mechanisms involved in the vasorelaxant effects of (−)-epigallocatechin-3-gallate (EGCG). EGCG (1 μM–1 mM) concentration dependently relaxed, after a transient increase in tension, contractions induced by noradrenaline (NA, 1 μM), high extracellular KCl (60 mM), or phorbol 12-myristate 13-acetate (PMA, 1 μM) in intact rat aortic rings. In a Ca2+-free solution, EGCG (1 μM–1 mM) relaxed 1 μM PMA-induced contractions, without previous transient contraction. However, EGCG (1 μM–1 mM) did not affect the 1 μM okadaic acid-induced contractions. Removal of endothelium and/or pretreatment with glibenclamide (10 μM), tetraethylammonium (2 mM) or charybdotoxin (100 nM) plus apamin (500 nM) did not modify the vasorelaxant effects of EGCG. In addition, EGCG noncompetitively antagonized the contractions induced by NA (in 1.5 mM Ca2+-containing solution) and Ca2+ (in depolarizing Ca2+-free high KCl 60 mM solution). In rat aortic smooth muscle cells (RASMC), EGCG (100 μM) reduced increases in cytosolic free Ca2+ concentration ([Ca2+]i) induced by angiotensin II (ANG II, 100 nM) and KCl (60 mM) in 1.5 mM CaCl2-containing solution and by ANG II (100 nM) in the absence of extracellular Ca2+. In RASMC, EGCG (100 μM) did not modify basal generation of cAMP or cGMP, but significantly reversed the inhibitory effects of NA (1 μM) and high KCl (60 mM) on cAMP and cGMP production. EGCG inhibited the enzymatic activity of all the cyclic nucleotide PDE isoenzymes present in vascular tissue, being more effective on PDE2 (IC50∼17) and on PDE1 (IC50∼25). Our results suggest that the vasorelaxant effects of EGCG in rat aorta are mediated, at least in part, by an inhibition of PDE activity, and the subsequent increase in cyclic nucleotide levels in RASMC, which, in turn, can reduce agonist- or high KCl concentration-induced increases in [Ca2+]i. PMID:16299547

  20. 液相色谱-质谱法检测水产品中腹泻性贝类毒素%Determination of diarrhetic shellfish poisoning in shellfishes by ultrahigh pressure liquid chromatography coupled with tandem mass spectrometry

    Institute of Scientific and Technical Information of China (English)

    张艳萍; 傅晓航

    2015-01-01

    An ultrahigh pressure liquid chromatography‐triple quadruple tandem mass spectrometric method has been proposed for the determination of a diarrhetic shellfish poisoning ,okadaic acid (OA) .After cleaned up by solid‐phase extraction (SPE) on an Oasis HLB cartridge ,the analytes were analysed on UPLC BEH column . The quantitative and confirmatory determi‐nation of OA was performed by multiple reactions monitoring (MRM) mode .Results indicated that the calibration curve of OA is 1inear in the range of 10‐400 μg/L .The quantification limit of OA is 10 μg/kg .The mean recoveries at spiked concentration of 10 ,50 and 200 μg/kg are 79 .4%‐90 .7% and the relative standard deviations are 8 .21%‐10 .69% (n=6) .%建立了超高效液相色谱‐串联四级杆质谱法检测贝类中腹泻性贝类毒素大田软海绵酸(O A )的方法。样品均质后经85%甲醇水溶液提取,HLB固相萃取柱净化,采用ACQUITY BEH C8(50 mm ×2.1 mm ,1.7μm)色谱柱分离,在多反应监测模式(M RM )下进行串联质谱定性与定量分析和检测。O A在10~400μg/L范围内线性关系良好,在10、50、200μg/kg 添加水平下平均回收率为79.4%~90.7%,相对标准偏差为8.21%~10.69%(n=6),定量检出限为10μg/kg。

  1. Overexpression of PIP2;5 aquaporin alleviates effects of low root temperature on cell hydraulic conductivity and growth in Arabidopsis.

    Science.gov (United States)

    Lee, Seong Hee; Chung, Gap Chae; Jang, Ji Young; Ahn, Sung Ju; Zwiazek, Janusz J

    2012-05-01

    The effects of low root temperature on growth and root cell water transport were compared between wild-type Arabidopsis (Arabidopsis thaliana) and plants overexpressing plasma membrane intrinsic protein 1;4 (PIP1;4) and PIP2;5. Descending root temperature from 25°C to 10°C quickly reduced cell hydraulic conductivity (L(p)) in wild-type plants but did not affect L(p) in plants overexpressing PIP1;4 and PIP2;5. Similarly, when the roots of wild-type plants were exposed to 10°C for 1 d, L(p) was lower compared with 25°C. However, there was no effect of low root temperature on L(p) in PIP1;4- and PIP2;5-overexpressing plants after 1 d of treatment. When the roots were exposed to 10°C for 5 d, L(p) was reduced in wild-type plants and in plants overexpressing PIP1;4, whereas there was still no effect in PIP2;5-overexpressing plants. These results suggest that the gating mechanism in PIP1;4 may be more sensitive to prolonged low temperature compared with PIP2;5. The reduction of L(p) at 10°C in roots of wild-type plants was partly restored to the preexposure level by 5 mm Ca(NO(3))(2) and protein phosphatase inhibitors (75 nm okadaic acid or 1 μm Na(3)VO(4)), suggesting that aquaporin phosphorylation/dephosphorylation processes were involved in this response. The temperature sensitivity of cell water transport in roots was reflected by a reduction in shoot and root growth rates in the wild-type and PIP1;4-overexpressing plants exposed to 10°C root temperature for 5 d. However, low root temperature had no effect on growth in plants overexpressing PIP2;5. These results provide strong evidence for a link between growth at low root temperature and aquaporin-mediated root water transport in Arabidopsis.

  2. [Alkaline phosphatase in Amoeba proteus].

    Science.gov (United States)

    Sopina, V A

    2005-01-01

    In free-living Amoeba proteus (strain B), 3 phosphatase were found after disc-electrophoresis of 10 microg of protein in PAGE and using 1-naphthyl phosphate as a substrate a pH 9.0. These phosphatases differed in their electrophoretic mobilities - "slow" (1-3 bands), "middle" (one band) and "fast" (one band). In addition to 1-naphthyl phosphate, "slow" phosphatases were able to hydrolyse 2-naphthyl phosphate and p-nitrophenyl phosphate. They were slightly activated by Mg2+, completely inhibited by 3 chelators (EDTA, EGTA and 1,10-phenanthroline), L-cysteine, sodium dodecyl sulfate and Fe2+, Zn2+ and Mn2+ (50 mM), considerably inactivated by orthovanadate, molybdate, phosphatase inhibitor cocktail 1, p-nitrophenyl phosphate, Na2HPO4, DL-dithiothreitol and urea and partly inhibited by H2O2, DL-phenylalanine, 2-mercaptoethanol, phosphatase inhibitor cocktail 2 and Ca2+. Imidazole, L-(+)-tartrate, okadaic acid, NaF and sulfhydryl reagents -p-(hydroxy-mercuri)benzoate and N-ethylmaleimide - had no influence on the activity of "slow" phosphatases. "Middle" and "fast" phosphatases, in contrast to "slow" ones, were not inactivated by 3 chelators. The "middle" phosphatase differed from the "fast" one by smaller resistance to urea, Ca2+, Mn2+, phosphates and H2O2 and greater resistance to dithiothreitol and L-(+)-tartrate. In addition, the "fast" phosphatase was inhibited by L-cysteine but the "middle" one was activated by it. Of 5 tested ions (Mg2+, Cu2+, Mn2+, Ca2+ and Zn2+), only Zn2+ reactivated "slow" phosphatases after their inactivation by EDTA treatment. The reactivation of apoenzyme was only partial (about 35 %). Thus, among phosphatases found in amoebae at pH 9.0, only "slow" ones are Zn-metalloenzymes and may be considered as alkaline phosphatases (EC 3.1.3.1). It still remains uncertain, to which particular phosphatase class "middle" and "fast" phosphatases (pH 9.0) may belong.

  3. [Tartrate-resistant acid phosphatase in free-living Amoeba proteus].

    Science.gov (United States)

    Sopina, V A

    2002-01-01

    Tartrate-resistant acid phosphatase (TRAP) of Amoeba proteus (strain B) was represented by 3 of 6 bands (= electromorphs) revealed after disc-electrophoresis in polyacrylamide gels with the use of 2-naphthyl phosphate as a substrate at pH 4.0. The presence of MgCl2, CaCl2 or ZnCl2 (50 mM) in the incubation mixture used for gel staining stimulated activities of all 3 TRAP electromorphs or of two of them (in the case of ZnCl2). When gels were treated with MgCl2, CaCl2 or ZnCl2 (10 and 100 mM, 30 min) before their staining activity of TRAP electromorphs also increased. But unlike 1 M MgCl2 or 1 M CaCl2, 1 M ZnCl2 partly inactivated two of the three TRAP electromorphs. EDTA and EGTA (5 mM), and H2O2 (10 mM) completely inhibited TRAP electromorphs after gel treatment for 10, 20 and 30 min, resp. Of 5 tested ions (Mg2+, Ca2+, Fe2+, Fe3+ and Zn2+), only the latter reactivated the TRAP electromorphs previously inactivated by EDTA or EGTA treatment. In addition, after EDTA inactivation, TRAP electromorphs were reactivated better than after EGTA. The resistance of TRAP electromorphs to okadaic acid and phosphatase inhibitor cocktail 1 used in different concentrations is indicative of the absence of PP1 and PP2A among these electromorphs. Mg2+, Ca2+ and Zn2+ dependence of TRAP activity, and the resistance of its electromorphs to vanadate and phosphatase inhibitor cocktail 2 prevents these electromorphs from being classified as PTP. It is suggested that the active center of A. proteus TRAP contains zinc ion, which is essential for catalytic activity of the enzyme. Thus, TRAP of these amoebae is metallophosphatase showing phosphomonoesterase activity in acidic medium. This metalloenzyme differs from both mammalian tartrate-resistant PAPs and tartrate-resistant metallophosphatase of Rana esculenta.

  4. A Study of Current Interseismic Deformation of San Andreas Fault, San Bernardino Mountain section, using Interferometric Synthetic Aperture Radar

    Science.gov (United States)

    Nee, P.; Funning, G. J.

    2010-12-01

    The San Andreas fault (SAF) system accommodates a significant fraction of the relative movement between the Pacific and North American plates. In the past 250 years, no significant earthquake was recorded on the southernmost section of the SAF, and thus there exists a substantial ongoing earthquake hazard. Estimates of its slip deficit rate, made with various geologic and geodetic observations typically fall in the range 15-25 mm/yr, in the vicinity of the San Bernadino Mountains. Assuming the fault system slips at a constant rate of 20mm/yr, a slip deficit of 5 m would have accumulated since the last event, equivalent to a potential Mw 7.5 or larger earthquake. To understand how much strain is accumulating on the southern SAF system during the current interseismic period, we investigate the surface deformation using radar interferometry. We use the entire catalog of ERS and Envisat Synthetic Aperture Radar (SAR) data from a descending track well oriented for the SAF (track 399). 53 images from ERS spanning 1992 to late 2000, and 50 images from Envisat spanning 2003 to 2010 are used. We perform ratemap inversion (Biggs et al. 2007, GJI) to obtain an estimate of interseismic slip deficit rate, and Persistent Scatterer InSAR (PSI) analysis to investigate the tectonic and non-tectonic surface displacements across the region. The ratemap inversion algorithm involves simultaneous estimation of long wavelength orbital errors, construction of a ratemap by finding the best fitting rate of each pixel, and estimation of slip deficit rate using a half-space elastic dislocation model (Okada 1985, BSSA) calculated from a representative fault model. We constructed and tested different conceptual models based on the SCEC rectangular community fault model (CFM-R). We find that our ERS data are strongly affected by the postseismic deformation of the 1992 Mw 7.3 Landers Earthquake. We therefore estimate the slip rate using the Envisat dataset, which is much less affected by the

  5. A Fault Evolution Model Including the Rupture Dynamic Simulation

    Science.gov (United States)

    Wu, Y.; Chen, X.

    2011-12-01

    We perform a preliminary numerical simulation of seismicity and stress evolution along a strike-slip fault in a 3D elastic half space. Following work of Ben-Zion (1996), the fault geometry is devised as a vertical plane which is about 70 km long and 17 km wide, comparable to the size of San Andreas Fault around Parkfield. The loading mechanism is described by "backslip" method. The fault failure is governed by a static/kinetic friction law, and induced stress transfer is calculated with Okada's static solution. In order to track the rupture propagation in detail, we allow induced stress to propagate through the medium at the shear wave velocity by introducing a distance-dependent time delay to responses to stress changes. Current simulation indicates small to moderate earthquakes following the Gutenberg-Richter law and quasi-periodical characteristic large earthquakes, which are consistent with previous work by others. Next we will consider introducing a more realistic friction law, namely, the laboratory-derived rate- and state- dependent law, which can simulate more realistic and complicated sliding behavior such as the stable and unstable slip, the aseismic sliding and the slip nucleation process. In addition, the long duration of aftershocks is expected to be reproduced due to this time-dependent friction law, which is not available in current seismicity simulation. The other difference from previous work is that we are trying to include the dynamic ruptures in this study. Most previous study on seismicity simulation is based on the static solution when dealing with failure induced stress changes. However, studies of numerical simulation of rupture dynamics have revealed lots of important details which are missing in the quasi-static/quasi- dynamic simulation. For example, dynamic simulations indicate that the slip on the ground surface becomes larger if the dynamic rupture process reaches the free surface. The concentration of stress on the propagating crack

  6. Contribution of large submarine landslide to tsunami potential in the NE Atlantic region: The Gorringe Bank case study

    Science.gov (United States)

    Ramalho, Inês; Omira, Rachid; Baptista, Maria Ana; Miranda, Miguel; Terrinha, Pedro; Batista, Luis; Roque, Cristina

    2015-04-01

    Tsunami is recognized as a natural hazard, and it is now widely accepted that submarine mass-failures are one of possible tsunami sources. Various studies on tsunami-induced by submarine landslides were carried out based on a spontaneous trigger of the mass-failure. In this study we focus on the deep-water submarine landslide in the Gorringe Bank (GB) area, NE Atlantic. In particular, we investigate the contribution of such mass-failure, as an additional source, to tsunami potential. We assume that an initial tsunami is generated by a large earthquake in the south west Iberia margin area that also initiates the failure of the GB landslide. This mass-failure can play the role of a secondary source of tsunami and contribute to tsunami potential. We simulate the tsunami generation as combination between the sea free surface perturbation caused instantaneously by the earthquake and the initial wave generated progressively due to the slide motion. Okada's equations are employed to compute the initial tsunami induced by the earthquake. While, a multi-layers viscous shallow water (VSW) model is used to simulate the flow of the submarine mass failure and the resulting tsunami wave. To model the propagation and coastal impact of the tsunami resulted from a combination of earthquake and landslide, we use a non-linear shallow water model and a nested grid system that allow estimating properly near-shore wave heights and inundation. We consider a 1755-like earthquake of magnitude Mw8.5, and a landslide of an approximate volume of about 60 km3. The characteristics of the landslide come from the analysis of detailed marine geological data including the erosional area (dimensions and scarps) and the seismic profiles. The results are presents in terms of: i) evidences of submarine mass failures in the area of GB; ii) simulations of the slide motion and the resulting tsunami wave; iii) simulations of the tsunami generated by a combination of two triggers: earthquake and landslide

  7. Tsunami hazard assessment in Nice, France, and influence of uncertainties in source parameters

    Science.gov (United States)

    Fontaine, Agathe; Loevenbruck, Anne; Heinrich, Philippe; Gailler, Audrey; Hébert, Hélène

    2015-04-01

    Although the tsunami hazard on the French Mediterranean coast is still poorly known, potential tsunamigenic sources exist in the Western Mediterranean basin. Even though the water heights are moderate, generated waves and currents could reach busy beaches, harbors and other coastal structures. The European project ASTARTE aims at reaching a higher level of tsunami resilience in the North-East Atlantic and Mediterranean region (called NEAM by IOC-UNESCO). In this context, ASTARTE proposes to improve the knowledge of tsunami generation, develop methods for hazard, vulnerability and risk assessment, better understand local coastal effects and enhance tools for early warning system. 9 test sites, including Nice for the French coasts, have been selected all over the NEAM area. Nice is the largest city of the French Riviera and welcomes a very large number of tourists every year, notably for seaside activities. Moreover its waterfront hosts the second French airport and many other facilities. Our work focuses on the tsunami hazard assessment related to seismic sources. This study, based on a worst-case scenarios approach, is carried out using multigrid numerical simulations. Seismic sources are computed through the Okada elastic dislocation model and constrained with the seismological parameters of the rupture. The coseismic deformation provides the initial condition to solve the shallow water equations on which the tsunami propagation simulation is based. Nested computational grids allow taking into account the shoaling effect for the Nice area as well as the potential inundation. The French Litto3D project, led by SHOM (Service Hydrographique et Oceanographique de la Marine) and IGN (Institut National de l'Information Geographique et Forestiere) provides high resolution bathymetric and topographic data (1 to 5 meters of resolution) along the coastline. Our modeling thus gives detailed estimation of the wave impacts on Nice with a particular focus on three critical

  8. As dificuldades ensinam em cursos online

    Directory of Open Access Journals (Sweden)

    José Lauro Martins

    2015-12-01

     ReferênciasALMEIDA, F. Tecnologia e escola: nossas aliadas. In J. A. Valente et al., Formação de professores a distância e integração de mídias. São Paulo: Avercamp, 2007. ALMEIDA, M. E. & Valente, J. A. Tecnologias e Currículo: trajetórias convergentes ou divergentes? São Paulo: Paulus, 2011. BARBERO, J. Heredando el futuro. Pensar la educación desde la comunicación. Rev. Nómadas, Nº 5, 1996. BELLONI, M. Educação à distância. Campinas: Autores associados, 2003. BORGES, M. Apropriação das tecnologias de informação e comunicação pelos gestores educacionais. São Paulo: PUC (Tese de Doutorado em Educação, 2009. HASSMANN, H. Redes digitais e metamorfoses do aprender. Petropolis-RJ: Vozes, 2005. KENSKI, V. M. Educação e Tecnologia: O ritmo da informação. Campinas: Papirus, 2007. LÉVY, P. As Tecnologias da inteligência. São Paulo: Editora 34, 1993. LION, C. Mitos e Realidade da Tecnología Educacional. In E. Litwin, Educação á Distância: Temas para o debate de uma nova agenda educativa. Porto Alegre: Artes Médicas, 1997. MORAN, J., Masetto, M. & Behrens, M. Novas tecnologias e mediações pedagógicas. Campinas: Papirus, 2003. OKADA, A. Memorial reflexivo em cursos on-line: um caminho para avaliação formativa emancipadora. In J. A. Valente et al., Formação de professores a distância e integração de midias. São Paulo: Avercamp, 2007. POSTMAN, N. O fim da educação: Redefinindo o valor da escola. Rio de Janeiro: Graphia, 2002. SANTOS, E. & Alves, L. Praticas pedagógicas e tecnologias digitais. Rio de Janeiro: E-papers, 2006. SILVA, B. Educação e Comunicação. Braga: CEEP - Universidade do Minho, 1998. SILVA, B. A tecnologia é uma estratégia. In Paulo Dias & Varela de Freitas (org.. Actas da II Confer

  9. Phosphorylation of BK channels modulates the sensitivity to hydrogen sulfide (H2S).

    Science.gov (United States)

    Sitdikova, Guzel F; Fuchs, Roman; Kainz, Verena; Weiger, Thomas M; Hermann, Anton

    2014-01-01

    Gases, such as nitric oxide (NO), carbon monoxide (CO), or hydrogen sulfide (H2S), termed gasotransmitters, play an increasingly important role in understanding of how electrical signaling of cells is modulated. H2S is well-known to act on various ion channels and receptors. In a previous study we reported that H2S increased calcium-activated potassium (BK) channel activity. The goal of the present study is to investigate the modulatory effect of BK channel phosphorylation on the action of H2S on the channel as well as to recalculate and determine the H2S concentrations in aqueous sodium hydrogen sulfide (NaHS) solutions. Single channel recordings of GH3, GH4, and GH4 STREX cells were used to analyze channel open probability, amplitude, and open dwell times. H2S was measured with an anion selective electrode. The concentration of H2S produced from NaHS was recalculated taking pH, temperature salinity of the perfusate, and evaporation of H2S into account. The results indicate that from a concentration of 300 μM NaHS, only 11-13%, i.e., 34-41 μM is effective as H2S in solution. GH3, GH4, and GH4 STREX cells respond differently to phosphorylation. BK channel open probability (Po) of all cells lines used was increased by H2S in ATP-containing solutions. PKA prevented the action of H2S on channel Po in GH4 and GH4 STREX, but not in GH3 cells. H2S, high significantly increased Po of all PKG pretreated cells. In the presence of PKC, which lowers channel activity, H2S increased channel Po of GH4 and GH4 STREX, but not those of GH3 cells. H2S increased open dwell times of GH3 cells in the absence of ATP significantly. A significant increase of dwell times with H2S was also observed in the presence of okadaic acid. Our results suggest that phosphorylation by PKG primes the channels for H2S activation and indicate that channel phosphorylation plays an important role in the response to H2S.

  10. Role of RhoA in regulating the pump function of isolated lymphatics from hemorrhagic shock rats.

    Science.gov (United States)

    Si, Yong-Hua; Niu, Chun-Yu; Zhao, Zi-Gang; Zhang, Li-Min; Zhang, Yu-Ping

    2013-07-01

    The aim of this present study was to examine changes in RhoA protein levels and the role in RhoA in lymphatic contractility and reactivity after hemorrhagic shock. Levels of RhoA and phospho-RhoA in lymphatic tissue isolated from hemorrhagic shock rats were measured, and the contractility and reactivity to substance P of lymphatics isolated from control rats and rats subjected to shock 0.5 and 2 h were determined with an isolated lymphatic perfusion system at a transmural pressure of 3 cmH2O. At the same time, lymphatics isolated from rats subjected to shock 0.5 and 2 h were incubated with agonists and antagonists of RhoA/Rho kinase signaling. Contractile frequency, end-diastolic and end-systolic diameter, and passive diameter were recorded and used to calculate lymphatic tonic index, contractile amplitude, and fractional pump flow. After stimulation with a gradient of substance P, the differences between the preadministration and postadministration values of contractile frequency, contractile amplitude, tonic index, and fractional pump flow were calculated to further assess lymphatic reactivity. RhoA protein levels were significantly increased at 0.5 h after shock but decreased at 2 and 3 h after shock; p-Rho levels were initially increased after shock and subsequently decreased. The contractility and reactivity of 0.5-h-shocked lymphatics were significantly reduced by the RhoA antagonist C3 transferase and the Rho kinase antagonist Y-27632. The RhoA agonist U-46619 increased the contractility and reactivity of 2-h-shocked lymphatics, whereas Y-27632 suppressed the effect of U-46619. Okadaic acid, an inhibitor of myosin light-chain phosphatase, had no effect on the contractility of 2-h-shocked lymphatics, but improved lymphatic reactivity. These results suggest that RhoA is involved in the modulation of lymphatic pump function during hemorrhagic shock and that its effects may be mediated by Rho kinase and MLCP.

  11. Two-year outcomes of pro re nata ranibizumab monotherapy for exudative age-related macular degeneration in Japanese patients

    Directory of Open Access Journals (Sweden)

    Yamamoto A

    2013-04-01

    Full Text Available Akiko Yamamoto,1 Annabelle A Okada,1 Atsuhiko Sugitani,1,2 Daisuke Kunita,1 Tosho Rii,1 Reiji Yokota1 1Department of Ophthalmology, Kyorin University School of Medicine, Tokyo, Japan; 2Department of Ophthalmology, Kugayama Hospital, Tokyo, Japan Purpose: To describe outcomes of intravitreal ranibizumab using a pro re nata regimen for treatment-naive exudative age-related macular degeneration (AMD, in Japanese patients over the first 2 years. Methods: Clinical records were retrospectively reviewed of 48 eyes of 48 patients with treatment-naive exudative AMD who underwent intravitreal ranibizumab therapy. After three monthly injections (induction, patients were examined monthly, and subsequent injections were performed as needed (pro re nata for any residual activity, by fundus biomicroscopy and imaging studies, regardless of severity. Results: Twenty-nine (60% of the patients were men, and 19 (40% were women; the mean age was 76.1 years. Of the 48 eyes evaluated, 17 (35% had findings consistent with polypoidal choroidal vasculopathy, and five (10% with retinal angiomatous proliferation. A mean of 6.0 ranibizumab injections were given in the first year, 3.5 in the second year, and 9.5 over the 2-year period. The best-corrected visual acuity (logarithm of minimum angle of resolution improved significantly, from 0.35 at baseline to 0.21 at 12 months (P < 0.01, and remained stable at 0.21 at 24 months (P < 0.01. The mean central macular thickness decreased significantly, from 355.4 µm at baseline to 237.9 µm at 12 months (P < 0.01 and 247.7 µm at 24 months (P < 0.01. Conclusion: Improved visual acuity and decreased central macular thickness were observed and maintained over a 2-year period, in a Japanese population receiving 3 monthly induction injections followed by a pro re nata regimen of ranibizumab for exudative AMD. Keywords: optical coherence tomography, polypoidal choroidal vasculopathy, retinal angiomatous proliferation

  12. 早熟凝集染色体环法在山西太原事故受照射者生物剂量估算中的应用%Biological dose estimation by prematurely condensed chromosomes ring assay for five victims in Shanxi Taiyuan radiation accident

    Institute of Scientific and Technical Information of China (English)

    姚波; 艾辉胜; 李玉芳; 白娟; 周振山; 王军良; 满秋红; 邱丽娟; 刘广贤; 郭梅

    2013-01-01

    OBJECTIVE: To investigate the value of prematurely drug induced condensed chromosomes ring (PCC-R) assay in estimating the biological doses in the victims of radiation accident. METHODS:Samples of peripheral blood were collected from the five victims (subjects 1-5) of the radiation accident of Taiyuan,Shanxi,16 hours after the accident. Bone marrow samples were collected 23 h after and peripheral blood sample 24 h after the accident from subject 1. The frequencies of PCC-R in PCC cells obtained by Okadaic acid (OA) induction were counted. A biological dose estimation was performed by a dose-effect curve of PCC-R (1-20 Gy). The frequencies of the PCC-R for the 4 victims (subjects 2-5) were analyzed 31 days after the accident. The results from PCC-R assay were verified by dicentrics plus centric rings (dic+r),Cytokinesis-block micronuclei (CBMN) assay and physical method. RESULTS:No or rare PCC cells were observed in the peripheral blood cultures from subject 1. However,PCC cells were obtained from bone marrow cultures in subject 1 and in peripheral blood cultures from subject 2-5. The doses estimated for subject 1-5 were 12.4,3.6,3.2,1.7 and 1.5 Gy, respectively. A decrease of PCC-R frequencies were observed 31 days after the accident,and the extent of the decrease were 51%,69%,69% and 44% for the subjects 2-5,respectively,compared with the data 16 h after the accident. The estimated doses were in accordance with those doses estimated by dic+r,CBMN assay,physical method and clinical symptoms. CONCLUSION:Drug induced PCC-R assay is convenient and rapid,and the new curve of PCC-R is accurate and reliable. It is especially suitable for estimating higher dose of irradiation. However,blood samples should be collected as soon as possible and should be done within one month after the accident.%目的:探讨药物诱导的早熟凝集染色体环 (prematurely condensed chromosomes ring,PCC-R)分析方法在辐射事故受照射者生

  13. PREFACE: The 16th International Symposium on Boron, Borides and Related Materials (ISBB 2008)

    Science.gov (United States)

    Tanaka, Takaho

    2009-07-01

    supported by Tokyo University of Science, Suwa and foundations including, the Kajima Foundation, Foundation for Promotion of Material Science and Technology of Japan and Nippon Sheet Glass Foundation for Materials Science and Engineering, as well as companies including JFE Steel Corporation, Shincron Co, Ltd, Toyo Kohan Co, Ltd, Fukuda Metal Foil and Powder Co, Ltd, Japan New Metals Co, Ltd, H C Starck Ltd and Fritsch Japan Co, Ltd. Editors Chair Takaho Tanaka (National Institute for Materials Science, Japan) Vice chairs Koun Shirai (Osaka University, Japan) Kaoru Kimura (The University of Tokyo, Japan) Ken-ichi Takagi (Tokyo City University, Japan) Touetsu Shishido (Tohoku University, Japan) Shigeru Okada (Kokushikan University) Hideaki Itoh (Nagoya University,Japan) Katsumitsu Nakamura (Nihon University, Japan) Organizing committee of ISBB 2008 K Takagi Chairman (Tokyo City University) T Tanaka Program Committee Chairman (National Institute for Materials Science) K Kimura Secretary (The University of Tokyo) J Akimitsu (Aoyama University)K Shirai (Osaka University) H Itoh (Nagoya University)T Shishido (Tohoku University) K Nakamura (Nihon University)K Soga (Tokyo University of Science) K Nishiyama (Tokyo University of Science, Suwa)M Takeda (Nagaoka University of Technology) S Okada (Kokushikan University)Y Yamazaki (Toyo Kohan Co, Ltd) International Scientific Committee 0f ISBB (2008-2011) K Takagi Chairman (Japan) B Albert (Germany) J-F Halet (France) M Takeda (Japan) M Antadze (Georgia) H Hillebrecht (Germany) T Tanaka (Japan) J Bauer (France) W Jung (Germany) R Telle (Germany) I Boustani (Germany) K Kimura (Japan) M Trenary (USA) D Emin (USA) T Mori (Japan) O Tsagareishvili (Georgia) M Engler (Germany) P D Ownby (USA) H Werheit (Germany) N Frage (Israel) P Rogl (Austria) G Will (Germany) Yu Grin (Germany) S Shalamberidze (Georgia) O Yucel (Turkey) V N Gurin (Russia) N Shitsevalova (Ukraine) G Zhang (China)

  14. Tsunami focusing and leading wave height

    Science.gov (United States)

    Kanoglu, Utku

    2016-04-01

    and Synolakis, 1994, Proc. R. Soc. A: Math. Phys. Eng. Sci., 445, 99-112) with a finite crest length, which is most common tsunami initial waveform. We fit earthquake initial waveform calculated through Okada (1985, Bull. Seismol. Soc. Am. 75, 1135-1040) to the N-wave form presented by Tadepalli and Synolakis (1994). First, we investigate focusing phenomena as presented by Kanoglu et al. (2013, Proc. R. Soc. A: Math. Phys. Eng. Sci., 469, 20130015) and compare our results with their non-dispersive and dispersive linear analytical solutions. We confirm focusing phenomena, which amplify the wave height in the leading depression side. We then study sequencing of an N-wave profile with a finite crest length. Our preliminary results show that sequencing is more pronounced on the leading depression side. We perform parametric study to understand sequencing in terms of N-wave, hence earthquake, parameters. We then discuss the results both in terms of tsunami focusing and leading wave amplitude. Acknowledgment: The research leading to these results has received funding from the European Union's Seventh Framework Programme (FP7/2007-2013) under grant agreement no 603839 (Project ASTARTE - Assessment, Strategy and Risk Reduction for Tsunamis in Europe).

  15. Hyperphosphorylation and accumulation of neurofilament proteins in Alzheimer brain and the possible mechanism

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Alzheimer disease (AD) neurofibrillary degeneration is characterized by a disruption of the cytoskeleton. The alteration of microtubule system and the microtubule-associated protein has been extensively investigated in this pathology. In the present study, we decided to explore the role of neurofilament (NF) proteins in AD neurofibrillary degeneration. We first investigated the content and the phosphorylation level of NF proteins in AD brain by using a panel of anti-NF antibodies. It was found by quantitative Western blot that the NF subunits were exclusively detected in an insoluble fraction from AD brain grey matter. The level of phosphorylated (p)-NF-H and (p)-NF-M was increased 1.5 and 1.3 times (P<0.05) respectively at phosphorylation specific antibody SMI31 epitope in AD as compared to neurological controls of Huntington disease (HD). A 1.6 fold elevation (P>0.05) of p-NF-H to another phosphate reactive antibody SMI34 was also seen in AD. The level of non-phosphorylated (np)-NF-H/M recognized by SMI33 was similar before alkaline phosphatase (ALP) treatment, but the total level of NF-H/M was 1.5 and 1.6 times (P<0.01) higher in AD than HD after dephosphorylation. Furthermore, a 1.8 fold increase of NF-M to SMI32 was observed in AD only after ALP treatment, suggesting that the NF-H/M are increased in the phosphorylated form. The amount of NF-L determined by NR-4 was 1.6 fold (P<0.01) higher in AD than HD. To our knowledge, this is the first biochemical data shown definite abnormality of NF subunits in AD brain. To understand the possible mechanism for the abnormal hyperphosphorylation and elevation of NF in AD brain, we treated human SY5Y neuroblastoma cell with protein phosphatase(PP)-2A and PP-1 inhibitor okadaic acid(OA). Then, we determined the relationship between an AD-like PP-A and PP-1 activity deficiency and NF phosphorylation as well as intracellular translocation in modeled cell system. It was demonstrated that p-NF-H/M detected by SMI31 and

  16. A New Method for Detecting Goaf Area of Coal Mine :2D Microtremor Profiling Technique

    Science.gov (United States)

    Xu, P.; Ling, S.; Guo, H.; Shi, W.; Li, S.; Tian, B.

    2012-12-01

    A goaf area is referred to as a cavity where coal has been removed or mined out. These cavities will change the original geostress equilibrium of stratigraphic system and cause local geostress focusing or concentration. Consequently, the surrounding rock of a goaf may be deformed, fractured, displaced and caved resulting from the combined effect of gravity and geostress. In the cases of little or no effective mining control, widespread cracks, fractures and even subsidence of the rock mass above the goaf will not only lead to groundwater depletion, farmland destruction and deterioration of ecological environment, but also present a serious threat to the mining safety, engineering construction, and even people's lives and property. So, it is important to locate the boundary of the goaf and to evaluate its stability in order to provide the basis for comprehensive control in the latter period of mining. This article attempts to explore a new geophysical method - 2D microtremor profiling technique for goaf detection and mapping. 2D microtremor profiling technique is based on the microtremor array theory (Aki, 1957; Ling, 1994; Okada, 2003) utilizing spatial autocorrelation analysis to obtain Rayleigh-wave dispersion curves for apparent S-wave velocity (Vx) calculation (Ling & Miwa, 2006;Xu et al.,2012). A laterally continuous S-wave velocity section can then be obtained through data interpolation. The final result will be used for interpreting lateral changes in lithology and geological structures. Let's take a case study in Henan Province of China as an example. The coal seams in the survey area were about 150 ~ 250m deep. A triple-circular array was adopted for acquiring microtremor data, with the observation radius in 20, 40 and 80m, respectively, and a sampling the interval of 50m. We observed the following characteristics of the goaf area from the microtremor Vx section: (1) obvious low pseudo velocity anomaly corresponding to limestone layer below the goaf; (2

  17. Recent Trends in Marine Phycotoxins from  Australian Coastal Waters

    Directory of Open Access Journals (Sweden)

    Penelope Ajani

    2017-02-01

    Full Text Available Phycotoxins, which are produced by harmful microalgae and bioaccumulate in the  marine food web, are of growing concern for Australia. These harmful algae pose a threat to  ecosystem and human health, as well as constraining the progress of aquaculture, one of the fastest  growing food sectors in the world. With better monitoring, advanced analytical skills and an  increase in microalgal expertise, many phycotoxins have been identified in Australian coastal  waters in recent years. The most concerning of these toxins are ciguatoxin, paralytic shellfish  toxins, okadaic acid and domoic acid, with palytoxin and karlotoxin increasing in significance. The  potential for tetrodotoxin, maitotoxin and palytoxin to contaminate seafood is also of concern,  warranting future investigation. The largest and most significant toxic bloom in Tasmania in 2012  resulted in an estimated total economic loss of~AUD$23M, indicating that there is an imperative to  improve  toxin  and  organism  detection  methods,  clarify  the  toxin  profiles  of  species  of  phytoplankton and carry out both intra‐ and inter‐species toxicity comparisons. Future work also  includes the application of rapid, real‐time molecular assays for the detection of harmful species  and toxin genes. This information, in conjunction with a better understanding of the life histories  and  ecology  of  harmful  bloom  species,  may  lead  to  more  appropriate  management  of  environmental, health and economic resources.

  18. Spontaneous Ventral Spinal Epidural Hematoma in an Infant: An Unusual Presentation

    Directory of Open Access Journals (Sweden)

    Asad ABBAS

    2013-06-01

    disorders of the spinal cord, in Davidoff RA (ed: Handbook of the Spinal Cord.Infections and Cancer, Vol 5. New York: Marcel Dekker, 1986, pp 271-273.8. Blount J, Doughty K, Tubbs RS, Wellons JC, Reddy A, Law C, et al. In utero spontaneous cervical thoracicepidural hematoma imitating spinal cord birth injury. Pediatr Neurosurg 2004;40:23-7.9. Iguchi T, Ito Y, Asai M, Ito J, Okada N, Murakami M. [A case of spontaneous spinal epidural hematoma]. No ToHattatsu 1993;25:267-70. Review. Japanese.10. Nagel MA, Taff IP, Cantos EL, Patel MP, Maytal J, Berman D. Spontaneous spinal epidural hematoma in a7-year-old girl. Diagnostic value of magnetic resonance imaging. Clin Neurol Neurosurg 1989;91:157-60.11. Metzger G, Singbartl G. Spinal epidural hematoma following epidural anesthesia versus spontaneous spinalsubdural hematoma. Two case reports. Acta Anaesthesiol Scand 1991;35:105-7.12. Patel H, Garg BP. Increasing irritability with sudden onset of flaccid weakness. Semin Pediatr Neurol 1996;3:192-7.13. Tewari MK, Tripathi LN, Mathuriya SN, Khandelwal N, Kak VK. Spontaneous spinal extradural hematomain children. Report of three cases and a review of the literature. Childs Nerv Syst 1992;8:53-5. Review.14. Pecha MD, Able AC, Barber DB, Willingham AC. Outcome after spontaneous spinal epidural hematoma in children: case report and review of the literature. Arch Phys Med Rehabil 1998;79:460-3. Review.

  19. Exploring variations in upper ocean structure for the last 2Ma of the Nansha area by means of calcareous nannofossils

    Institute of Scientific and Technical Information of China (English)

    LlU; Chua; nlian

    2001-01-01

    [1]Molfino, B., Mclntyre, A., Precessional forcing of nutricline dynamics in the Equatorial Atlantic, Science, 1990, 249:766-769.[2]Ahagon, N., Tanaka, Y., Ujiie, H., Florisphaera profunda, a possible nannoplankton indicator of late quaternary changes in seawater turbidity at the northwestern margin of the Pacific, Marine Micropaleontology, 1993, 22: 255-273.[3]Cheng, X., Wang, P, Variations in late Quaternary upper ocean structure of Okinawa Trough: A nannofossil approach,Science in China, Ser. D, 1998, 41(3): 290-296.[4]Okada, H., Matsuoka, M., Lower-photic nannoflora as an indicator of the late Quaternary monsoonal palaeo-record in the tropical Indian Ocean, in Micro-fossils and Oceanic Environments (eds. Moguilevsky, A., Whatley, R.), University of Wales, Aberystwyth Press, 1996, 231-245.[5]Beaufort, L., Lancelot, Y., Camberlin, P. et al., Insolation cycles as a major control of equatorial Indian Ocean primary production, Science, 1997, 278: 1451-1454.[6]Bassinot, F. C., Beaufort, L., Vincent, E. et al., Changes in the Dynamics of western Equatorial Atlantic surface current sand biogenic productivity at the “Mid-Pleistocene Revolution“ (930 ka), in Proceedings of the Ocean Drilling Program,Scientific Results (eds. Shackleton, N. J., Curry, W. B., Richter, C.), 1997, 154: 269-284.[7]Castradori, D., Calcareous nannofossils and the origin of eastern Mediterranean sapropels, Paleoceanography, 1993, 8(4):459-471.[8]Baumann, K. H., Cepek, M., Kinkel, H., Coccolithophores as indicators of ocean water masses, surface-water temperature,and paleoproductivity Examples from the South Atlantic, in Use of Proxies in Paleoceanography: Examples from the South Atlantic (eds. Fischer, G., Wefer, G.), Heidelberg: Springer-Verlag, 1999, 111-144.[9]Kinkel, H., Baumann, K. H., Cepek, M., Coccolithophores in the equatorial Atlantic Ocean: Response to seasonal and Late Quaternary surface water variability, Marine Micropaleontology, 2000, 39

  20. Tectonic dynamics of the Lipari-Vulcano islands revealed by geodetic and seismic data

    Science.gov (United States)

    Gambino, S.; Alparone, S.; Bonforte, A.; Gresta, S.; Guglielmino, F.; Obrizzo, F.; Puglisi, G.

    2009-12-01

    the area covered by the Lipari-Vulcano network. Transpressive kinematics of the Lipari-Vulcano volcanic complex, with a main N-S contraction and a minor E-W extension only on the Southern part of Vulcano is revealed. In addition, data inversion was performed using a simple Okada model, inverting the horizontal strain measured on 258 GPS baselines. We prefer using baselines rather than displacement vectors to avoid bias due to the ambiguity in fixing the reference system. The final structural framework defines a main compression with a dextral component of displacement on a NW-SE striking structure. This kinematics agrees with focal mechanisms of the strongest seismic events recorded in this area over the same time span as the GPS surveys. Furthermore, a preliminary analysis shows that the observed tilt fits well with the expected one from the model.

  1. Effectiveness of music therapy: a summary of systematic reviews based on randomized controlled trials of music interventions

    Directory of Open Access Journals (Sweden)

    Kamioka H

    2014-05-01

    Full Text Available Hiroharu Kamioka,1 Kiichiro Tsutani,2 Minoru Yamada,3 Hyuntae Park,4 Hiroyasu Okuizumi,5 Koki Tsuruoka,6 Takuya Honda,7 Shinpei Okada,8 Sang-Jun Park,8 Jun Kitayuguchi,9 Takafumi Abe,9 Shuichi Handa,5 Takuya Oshio,10 Yoshiteru Mutoh111Faculty of Regional Environment Science, Tokyo University of Agriculture, Tokyo, Japan; 2Department of Drug Policy and Management, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan; 3Kyoto University Graduate School Research, Kyoto, Japan; 4Department of Functioning Activation, National Center for Geriatrics and Gerontology, Aichi, Japan; 5Mimaki Onsen (Spa Clinic, Tomi, Nagano, Japan; 6Graduate School of Social Services, Japan College of Social Work, Tokyo, Japan; 7Japanese Society for the Promotion of Science, Tokyo, Japan; 8Physical Education and Medicine Research Foundation, Tomi, Nagano, Japan; 9Physical Education and Medicine Research Center Unnan, Shimane, Japan; 10Social Welfare Service Corporation CARE-PORT MIMAKI, Tomi, Nagano, Japan; 11The Research Institute of Nippon Sport Science University, Tokyo, JapanObjective: The objective of this review was to summarize evidence for the effectiveness of music therapy (MT and to assess the quality of systematic reviews (SRs based on randomized controlled trials (RCTs.Study design: An SR of SRs based on RCTs.Methods: Studies were eligible if they were RCTs. Studies included were those with at least one treatment group in which MT was applied. We searched the following databases from 1995 to October 1, 2012: MEDLINE via PubMed, CINAHL (Cumulative Index of Nursing and Allied Health Literature, Web of Science, Global Health Library, and Ichushi-Web. We also searched all Cochrane Database and Campbell Systematic Reviews up to October 1, 2012. Based on the International Classification of Diseases, 10th revision, we identified a disease targeted for each article.Results: Twenty-one studies met all inclusion criteria. This study included 16

  2. 新疆于田Mw7.2地震3D同震形变场解算与分析%CALCULATION AND ANALYSIS OF THREE-DIMENSIONAL CO-SEISMIC DEFORMATION FIELD CAUSED BY XINJIANG YUTIAN Mw7.2 EARTHQUAKE

    Institute of Scientific and Technical Information of China (English)

    洪顺英; 单新建; 刘智荣; 申旭辉; 戴娅琼; 荆凤

    2013-01-01

    基于OKADA弹性半空间模型和差分干涉测量获取的升、降轨两种不同视角的同震形变场,分析了于田地震三维同震形变场特征.结果表明:在垂直方向上,断层西盘沉降,最大沉降形变量达-109.7 cm,东盘隆升,最大隆升形变量为19.2 cm;在东西方向上,断层西盘以朝西运动为主,最大形变量达-51.4 cm,东盘朝东运动,最大形变量达98.5 cm;在南北方向上,断裂西盘以朝南运动为主,最大形变量达-66.5 cm,断裂东盘朝北运动,最大形变量为25.8 cm;合成后的水平向形变表明,断层具有西盘朝南走滑、东盘朝北走滑的形变特征,揭示出于田地震断层为正断兼左旋走滑的破裂机制.%On the basis of the elastic half-space model of OKADA, and under the constraint of interferograms, We obtained the parameters of three sub-faults and simulative three-dimensional(3D) deformation field of the Yu-tian Mw7. 2 earthquake, Xinjiang. Furthermore, combining the simulative North direction deformation field with the interferograms of ascending and descending oribt, we calculated out the deformation fields in vertical and east direction. At last, we analyzed the characteristics of 3D co-seismic deformation field of the Yutian earthquake. The analysis shows that in the vertical direction, the west wall of the fault subside with maximal value about - 109. 7 cm, but the east wall uplifted with maximum value about 19. 2 cm, and the dominant subsiding deformation feature indicates the mostly normal rupture feature of the earthquake; in the east-west direction, the west wall majorly moved west wards with maximal value about -51.4 cm, but the east wall majorly moved east wards with maximal value about 98.5 cm;in the north-south direction, the west wall majorly moved south wards with maximal value about -66. 5 cm, but the east wall majorly moved north wards with maximal value about 25. 8 cm. The synthetic horizontal deformation field indicates that the west

  3. Epstein-Barr Virus Encephalitis: A Case Report

    Directory of Open Access Journals (Sweden)

    Somayh HASHEMIAN

    2015-01-01

    Full Text Available How to Cite This Article: Hashemian S, Ashrafzadeh F, Akhondian J, Beiraghi Toosi M. Epstein-Barr Virus Encephalitis: A Case Report. Iran J Child Neurol. 2015 Winter;9(1:107-110.  Abstract Many neurologic manifestations of Epstein-Barr virus (EBV infection have been documented, including encephalitis, aseptic meningitis, transverse myelitis, and Guillain-Barre syndrome. These manifestations can occur alone or coincidentally with the clinical picture of infectious mononucleosis. EBV encephalitis is rare and is indicated as a wide range of clinical manifestations. We report a 10-year-old girl presented with fever, gait disturbance, and bizarre behavior for one week. The results of the physical examination were unremarkable. The diagnosis of EBV encephalitis was made by changes in titers of EBV specific antibodies and MRI findings. A cranial MRI demonstrated abnormal high signal intensities in the basal ganglia and the striatal body, especially in the putamen and caudate nucleus. EBV infection should be considered when lesions are localized to the basal ganglia.ReferencesFujimoto H, Asaoka K, Imiazumi T, Ayabe M, Shoji H, Kaji M. Epstein-Barr virus Infections of the Central Nervous System. Intern Med 2003; 42:33-40.Mathew AG, Parvez Y. Fulminant Epstein Barr virus encephalitis. Indian Pediatrics 2013; 50:418-419Kalita J, Maurya PK, Kumar B, Misra UK. Epstein Barr virus encephalitis: Clinical diversity and radiological similarity. Neurol India 2011; 59:605-7Baskin HJ, Hedlund G. Neuroimaging of Herpes Virus Infections in Children. Pediatr Radiol 2007; 37:949-63.Weinberg A, Li SH, Palmer M, Tyler K .Quantitative CSF PCR in Epstein-Barr Virus Infections of the Central Nervous System. Ann Neurol 2002; 52:543-8.Ono J, Shimizu K, Harada k, Mano T, Okada S. Characteristic MR Features of Encephalitis Caused by Epstein-Barr virus. Pediatr Radiol 1998; 28:569-70.Hausler M, Raamaekers T, Doenges M, Shweizer K ,Ritter K. Neurological Complications of Acute

  4. Regional variation of carbonaceous aerosols from space and simulations

    Science.gov (United States)

    Mukai, Sonoyo; Sano, Itaru; Nakata, Makiko; Kokhanovsky, Alexander

    2017-04-01

    effect on carbonaceous aerosols. And then the selected data observed by ADEOS-2/GLI and POLDER in 2003 are treated by using Vector form Method of Successive Order of Scattering (VMSOS) for radiative transfer simulations in the semi-infinite atmosphere [2]. Finally the obtained optical properties of the carbonaceous aerosols are investigated in comparison with the numerical model simulations of SPRINTARS. In spite of the limited case studies, it has been pointed out that NUV-channel data are effective for retrieval of the carbonaceous aerosol properties. Therefore we have to treat with this issue for not only detection of biomass burning plume but also retrieval itself. If that happens, synthetic analysis based on multi-channel and/or polarization measurements become practical, and the proposed procedure and results are available for a feasibility study of coming space missions. [1] Sano, I., Y. Okada, M. Mukai and S. Mukai, "Retrieval algorithm based on combined use of POLDER and GLI data for biomass aerosols," J. RSSJ, vol. 29, no. 1, pp. 54-59, doi:10.11440/rssj.29.54, 2009. [2] Mukai, S., M. Nakata, M. Yasumoto, I. Sano and A. Kokhanovsky, "A study of aerosol pollution episode due to agriculture biomass burning in the east-central China using satellite data," Front. Environ. Sci., vol. 3:57, doi: 10.3389/fenvs.2015.00057, 2015.

  5. Precursor to the Matuyama/Brunhes Polarity Transition 0.78 Million Years Ago at Bishop, CA

    Science.gov (United States)

    Kravchinsky, Vadim; Liddicoat, Joseph

    2013-04-01

    Van Zijl et al.'s 1962 report of a polarity transition in Stormberg lavas was the first of many investigations of the Matuyama/Brunhes polarity transition (MBPT) about 0.78 m.y. ago. Among the earliest of those investigations was a study of bathyal siltstone in the Boso Peninsula in Japan (Niitsuma, 1971; Okada and Niitsuma, 1989). That investigation was preceded by a report that the relative intensity of the palaeomagnetic field as recorded in a marine core is reduced for a longer period of time than is required for the field directions to reverse (Ninkovich et al., 1966), a discovery that was summarized for other reversals in cored marine sediment (Opdyke, 1973). In the U.S., Hillhouse and Cox (1976) documented the field directions and relative intensity during the MBPT using exposed Pleistocene Lake Tecopa sediments in southeastern California. They reported a generally smooth path of the Virtual Geomagnetic Poles (VGPs) as the field changed from reverse to normal that does not coincide with the VGP path for the MBPT in Japan, concluding that the transitional field is predominantly the non-dipole field. At Lake Tecopa, as in the marine record, the reduction in field strength occurred sooner and lasted longer by a factor of at least two the time required for the directions to reverse polarity, which was confirmed by Valet et al. (1988) in a restudy of the Lake Tecopa sediments. The Lake Tecopa study by Hillhouse and Cox (1976) was followed by one of Pleistocene lacustrine sediments exposed beneath the Bishop Tuff (Dalrymple et al., 1965) near Bishop, California (37.4˚ N, 241˚ E) (Liddicoat, 1982, 1993). The data we report are for directional and normalized relative intensity measurements of additional samples from each horizon at the Bishop locality that indicate the time spanned by the reduction in relative intensity for the full transition exceeds by about 20 percent the time during which the palaeomagnetic directions reverse. Although the change in field

  6. Generation of deterministic tsunami hazard maps in the Bay of Cadiz, south-west Spain

    Science.gov (United States)

    Álvarez-Gómez, J. A.; Otero, L.; Olabarrieta, M.; González, M.; Carreño, E.; Baptista, M. A.; Miranda, J. M.; Medina, R.; Lima, V.

    2009-04-01

    free surface elevation, maximum water depth, maximum current speed, maximum Froude number and maximum impact forces (hydrostatic and dynamic forces). The fault rupture and sea bottom displacement has been computed by means of the Okada equations. As result, a set of more than 100 deterministic thematic maps have been created in a GIS environment incorporating geographical data and high resolution orthorectified satellite images. These thematic maps form an atlas of inundation maps that will be distributed to different government authorities and civil protection and emergency agencies. The authors gratefully acknowledge the financial support provided by the EU under the frame of the European Project TRANSFER (Tsunami Risk And Strategies For the European Region), 6th Framework Programme.

  7. Tsunami hazard assessment along the U. S. East Coast

    Science.gov (United States)

    Tajalli Bakhsh, T.; Grilli, S. T.; Harris, J. C.; Kirby, J. T.; Shi, F.; Tehranirad, B.

    2012-12-01

    sources are modeled using the standard Okada method. For landslide tsunamis, we first generate tsunami sources using a three-dimensional Navier-Stokes model (THETIS or NHWAVE). These models feature all relevant physical processes, such as frequency dispersion (very important for landslide sources), nonlinear wave effects during shoaling, and dissipation by bottom friction and wave breaking (via a shock-capturing TVD algorithm). In modeling coastal hazard from various sources, we find that tsunamigenic SMFs, which are the nearest tsunami sources and can potentially cause highly focused coastal runup, may control tsunami hazard for many east coast communities north of the Carolinas. In many cases, however, we find that a wide shallow continental shelf may cause significant dissipation of the shorter waves caused by SMFs and hence offer some protection. The accurate modeling of the delicate balance between nonlinear and dissipative processes governing such situations is currently being researched and will be the object of a separate presentation. Additionally, considerable efforts are being devoted to properly parameterizing extreme SMFs, which are also the object of collaborative work with geologists and marine geotechnical experts (reported independently).

  8. Uncovering deformation processes from surface displacements

    Science.gov (United States)

    Stramondo, Salvatore

    2013-04-01

    geophysical data, such as teleseismic waveforms, strong motion records and GPS, have also been used by geophysicists for improved rupture models. Many models use equations for a uniform elastic half space stemming from the Okada formulation, but improved data constraints and the use of increasingly sophisticated modeling and inverse methods allowed for the exploration of models with variation of elastic properties in layers or more complex representation of fault and lithosphere structure and rheology. In volcanic studies the role of GPS and InSAR lies in the measurement of pre-eruptive inflation, co-eruptive deflation and the post-eruptive response. The spatio-temporal evolution of volcanic processes, the "breathing" of a volcano, can be monitored with temporal series of InSAR interferograms using multitemporal InSAR techniques. The measured deformation can be used as constraints for the formulation of the inverse problem, to retrieve information concerning the depth, size, shape of the magma chamber (and pressure change) and magma supply dynamics. Deformation modeling commonly relies on simple point sources, dikes and sills; or more complex volume-change sources to produce the different surface deformation patterns caused by magma intrusion.

  9. Involvement of the dehydroleucodine alpha-methylene-gamma-lactone function in GVBD inhibition in Bufo arenarum oocytes.

    Science.gov (United States)

    Sánchez Toranzo, G; López, L A; Martínez, J Zapata; Bühler, M C Gramajo; Bühler, M I

    2010-02-01

    Dehydroleucodine (DhL), a sesquiterpenic lactone, was isolated and purified from aerial parts of Artemisia douglasiana Besser, a medicinal herb used in Argentina. DhL is an alpha-methylene butyro-gamma-lactone ring connected to a seven-membered ring fused to an exocyclic alpha,beta-unsaturated cyclopentenone ring. It has been previously shown that DhL selectively induces a dose-dependent transient arrest in G2 of both meristematic cells and vascular smooth muscle cells. Treatment with DhL induces an inhibition of spontaneous and progesterone-induced maturation in a dose-dependent manner in Bufo arenarum fully grown oocytes arrested at G2, at the beginning of meiosis I. However, the nature of the mechanisms involved in the process is still unknown. The aim of this work was to analyse whether DhL's alpha-methylene-gamma-lactone function is responsible for the inhibition effect on meiosis reinitiation of Bufo arenarum oocytes as well as some of the transduction pathways that could be involved in this effect using a derivative of DhL inactivated for alpha-methylenelactone, the 11,13-dihydro-dehydroleucodine (2H-DhL). The use of 2H-DhL in the maturation promoting factor (MPF) amplification experiments by injection of both cytoplasm with active MPF and of germinal vesicle content showed results similar to the ones obtained with DhL, suggesting that the hydrogenated derivative would act in a similar way to DhL. Pretreatment with DhL or 2H-DhL did not affect the percentage of germinal vesicle breakdown (GVBD) induced by H89, a protein kinase A (PKA) inhibitor, which suggests that these lactones would act on another step of the signalling pathway that induces MPF activation. The fact that both DhL and 2H-Dhl inhibit GVBD induced by okadaic acid microinjection suggests that they could act on the activity of the Myt1 kinase. This idea is supported by the experiments of injection of GV contents in which an inhibitory effect of these lactones on GVBD was also observed. Our

  10. Long-term rates and the depth extent of fault creep along the San Andreas Fault system in northern California from alinement arrays and GPS data

    Science.gov (United States)

    Lienkaemper, J. J.; McFarland, F. S.; Simpson, R. W.; Caskey, J.

    2013-12-01

    The dextral San Andreas Fault system (SAFS) in northern California comprises five branches that exhibit considerable variation in the amount and spatial extent of aseismic release or creep. We estimate the depth extent of creep with a forward elastic model using the algorithms of Okada (1992) and boundary value dislocation solutions for creep rate and depth of creeping patches. For purposes of analysis we label branches, from west to east: A (San Gregorio), B (San Andreas), C (Calaveras-Hayward-Rodgers Creek-Maacama), D (Northern Calaveras-Green Valley-Bartlett Springs) and E (Greenville. Since the 1960s alinement arrays have provided one of the most accurate means to estimate the long-term creep rate and these rates have been reasonably well determined for much of the San Francisco Bay area (SFBA) southward. Over the past decade we have been installing alinement arrays along the more remote faults, especially northward of the SFBA, to monitor the extent of creep on branches C and D. We currently monitor about 80 such arrays throughout the northern SAFS. To analyze the depth extent of creep over the entire system, we model 30 fault sections on these five branches, delineated either by geometric discontinuities between them or by distinctly different creeping behaviors. We have removed any significant transient rate changes imposed by large regional earthquakes. We use crustal velocities determined for global-positioning station pairs of survey mode and continuous (SGPS, CGPS or mixed pairs) that are located near each fault to provide additional constraint on average creep rates. We estimate the mean depth of creep from the mean observed surface creep rate for each section and the rate uncertainty allows estimation of a depth uncertainty. Uncertainties are generally much higher where only five years or less of alinement array data are available, but in some cases the addition of CGPS or multiple SGPS station pairs has been essential for a more complete evaluation of

  11. Necessity of using heterogeneous ellipsoidal Earth model with terrain to calculate co-seismic effect

    Science.gov (United States)

    Cheng, Huihong; Zhang, Bei; Zhang, Huai; Huang, Luyuan; Qu, Wulin; Shi, Yaolin

    2016-04-01

    Co-seismic deformation and stress changes, which reflect the elasticity of the earth, are very important in the earthquake dynamics, and also to other issues, such as the evaluation of the seismic risk, fracture process and triggering of earthquake. Lots of scholars have researched the dislocation theory and co-seismic deformation and obtained the half-space homogeneous model, half-space stratified model, spherical stratified model, and so on. Especially, models of Okada (1992) and Wang (2003, 2006) are widely applied in the research of calculating co-seismic and post-seismic effects. However, since both semi-infinite space model and layered model do not take the role of the earth curvature or heterogeneity or topography into consideration, there are large errors in calculating the co-seismic displacement of a great earthquake in its impacted area. Meanwhile, the computational methods of calculating the co-seismic strain and stress are different between spherical model and plane model. Here, we adopted the finite element method which could well deal with the complex characteristics (such as anisotropy, discontinuities) of rock and different conditions. We use the mash adaptive technique to automatically encrypt the mesh at the fault and adopt the equivalent volume force replace the dislocation source, which can avoid the difficulty in handling discontinuity surface with conventional (Zhang et al., 2015). We constructed an earth model that included earth's layered structure and curvature, the upper boundary was set as a free surface and the core-mantle boundary was set under buoyancy forces. Firstly, based on the precision requirement, we take a testing model - - a strike-slip fault (the length of fault is 500km and the width is 50km, and the slippage is 10m) for example. Because of the curvature of the Earth, some errors certainly occur in plane coordinates just as previous studies (Dong et al., 2014; Sun et al., 2012). However, we also found that: 1) the co

  12. Sucrose-mediated transcriptional regulation of sucrose symporter activity in the phloem.

    Energy Technology Data Exchange (ETDEWEB)

    Matt Vaughn Greg Harrington Daniel R Bush

    2002-08-06

    This project was based on our discovery that sucrose acts as a signaling molecule that regulates the activity of a proton-sucrose symporter in sugar beet leaf tissue. A major objective here was determining how sucrose transporter activity is being regulated. When sucrose accumulates in the phloem sucrose transport activity drops dramatically. Western blots of plasma membrane proteins isolated from sucrose treated leaves showed that the loss of sucrose transport activity was proportional to a decline in symporter abundance, demonstrating that sucrose transport is regulated by changes in the amount of BvSUT1 protein. BvSUT1 transcript levels decreased in parallel with the loss of sucrose transport activity. Nuclear run-on experiments demonstrated that BvSUT1 gene transcription was repressed significantly in nuclei from leaves fed 100 mM exogenous sucrose, showing that sucrose-dependent modulation of BvSUT1 mRNA levels is mediated by changes in transcription. To identify which secondary messenger systems might be involved in regulating symporter activity, we used a variety of pharmacological agents to probe for a role of calcium or protein phosphorylation in sucrose signaling. In a detailed analysis, only okadaic acid altered sucrose transport activity. These results suggest a protein phosphatase is involved. We hypothesized that protein kinase inhibitors would have a neutral affect or increase symporter transcription. Transpirational feeding of the protein kinase inhibitor staurosporine had no impact on sucrose transport while calphostin C, an inhibitor of protein kinase C, caused a 60% increase. These data provided good evidence that protein phosphorylation plays a central role in regulating sucrose symporter expression and sucrose transport activity. To determine whether protein phosphorylation is involved in sucrose regulation of proton-sucrose symporter activity, we pre-fed leaves with staurosporine for 4 h and then fed the treated leaves water or 100 mM sucrose

  13. A Bayesian exploration of the distribution of aseismic slip along the creeping section of the San Andreas Fault, California

    Science.gov (United States)

    Jolivet, R.; Agram, P. S.; Simons, M.; Shen, Z.; Zhang, H.

    2013-12-01

    section. We discretize both fault planes into rectangular patches with sizes varying as a function of depth and compute the static displacement Green's functions in a continuous half space using Okada's solution and in a layered space. We use a massively parallel implementation of CATMIP, a bayesian solver optimized for GPUs, to determine the full posterior probability of each parameter, including slip rates on the shallow section of the SAF and CPF and slip rates on deep dislocations to account for the interseimic tectonic loading across the San Andreas fault system. Our results confirm the variable distribution of creep rates along strike and at depth. Maximum slip rate is inferred north of Parkfield, while it decays toward the north. We also highlight a close correlation between the location of micro- and moderate seismicity and patches of high slip rate.

  14. PREFACE AND CONFERENCE INFORMATION: Eighth International Conference on Laser Ablation

    Science.gov (United States)

    Hess, Wayne P.; Herman, Peter R.; Bäuerle, Dieter; Koinuma, Hideomi

    2007-04-01

    enjoy the collection of papers in this proceeding. Also, please join us for COLA 2007, to be held in the Canary Islands, Spain (http://www.io.csic.es/cola07/index.php). Conference on Laser Ablation (COLA'05) September 11-16, 2005 Banff, Canada Supported by University of Toronto, Canada (UT) Pacific Northwest National Laboratory (PNNL) Sponsors Sponsorship from the following companies is gratefully acknowledged and appreciated AMBP Tech Corporation GSI Lumonics Amplitude Systèmes IMRA America, Inc. Andor Technologies Journal of Physics D: Applied Physics North Canadian Institute for Photonic Innovations LUMERA LASER GmbH Clark-MXR, Inc. Pascal Coherent, Lamdbda Physik, TuiLaser PVD Products, Inc. Continuum Staib Instruments, Inc. Cyber Laser Inc. Surface GAM LASER, Inc. International Steering Committee C. Afonso (Spain)W. Husinsky (Austria) D. Bäuerle (Austria)W. Kautek (Germany) I.W. Boyd (UK) H. Koinuma (Japan) E.B. Campbell (Sweden) H.U. Krebs (Germany) J.T. Dickinson (USA) D.H. Lowndes (USA) M. Dinescu (Romania) J.G. Lunney (Ireland) J.J. Dubowski (Canada) W. Marine (France) E. Fogarassy (France) K. Murakami (Japan) C. Fotakis (Greece) T. Okada (Japan) D. Geohegan (USA) R.E. Russo (USA) M. Gower (UK) J. Schou (Denmark) R.H. Haglund Jr. (USA) M. Stuke (Germany) R.R. Herman (Canada) K. Sugioka (Japan) W.P. Hess (USA) F. Traeger (Germany) J.S Horwitz (USA) A. Yabe (Japan) Local Organizing Committee Nikki Avery Pacific Northwest National Laboratory Ken Beck Pacific Northwest National Laboratory Jan J. Dubowski University of Alberta Robert Fedosejevs Université de Sherbrooke Alan Joly Pacific Northwest National Laboratory Michel Meunier École Polytechnique de Montréal Suwas Nikumb National Research Council Canada Ying Tsui University of Alberta Conference photograph.

  15. 液相色谱结合串联质谱方法研究中国沿海贝类中脂溶性藻毒素的种类结构和分布规律%The Lipophilic Phycotoxins Profile and Distribution in Bivalve Shellfish of Chinese Coasts by High Performance Liquid Chromatography Coupled with Mass Spectrometry

    Institute of Scientific and Technical Information of China (English)

    刘仁沿; 梁玉波; 刘磊; 樊东红; 许道艳; 孙茜

    2014-01-01

    A number of marine microalgae are known to produce toxins that can accumulate in shellfish, leading to food poisons and potentially fatal reactions of humans and other mammals consuming the contaminated shellfish. Lipophilic phycotoxins are dissolvable in organic solvents, and easily accumulated in animal adipose tissue. There are six common types lipophilic phycotoxins with variety of structures for each. This paper reported the profiles and distributions of lipophilic phycotoxins in 34 bivalve species from 55 stations along the coasts of China. Multiple types of lipophilic phycotoxins were detected in the bivalves along the coasts of China through the HPLC-MS/MS method, including Okadaic acid (OA), Pectenotoxin (PTXs), Azaspiracid (AZAs), Yessotoxin (YTXs)、Gymnodimine(GYM) and Spiroloides(SPX)etc. GYM was mostly observed in the coastal water of Guangdong, Guangxi and Hainan in South China Sea;YTXs, mainly present in Patinopecten yessoensis and Chlamys farreri, were detected only in Yellow Sea; while PTXs were mostly from the coast of Bohai. We observed three structures of PTXs, among which, the one had highest positive rate of 44% and maximum tissue concentration of 53.2 µg·kg-1 were PTX-2Sa; In terms of positive rate and tissue concentration, GYM (35.3%,39.1 µg·kg-1) followed PTX-2Sa. Similarly, three structures of YTXs were detected. And YTXs were present in the tissues of Patinopecten yessoensis in northern Yellow Sea throughout the year with a peak concentration in September. The geographic distributions of phycotoxins could be depended on the presence of toxic algae, while it was still unclear about the biological source of these three common lipophilic phycotoxins detected in the shellfish in China. Although the level of lipophilic phycotoxins in this study were lower than the regulated limitation for food safety, the work here reported the wide presence of variety of phycotoxins in the shellfish along the coasts of China, posing potential health

  16. 2000年《照明工程学报》总目次

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Chromaticity- Discrimination Ellipses Huan Hui et al.(3-24) Influence of Colour Temperature and Colour Rendering of Lamp on Interior Light Environment Jin Hai et al.(3-27) Colour Standard and Image Display Cui Xianming et al.(3-30) Discussion on the Microwave Leakage of the Sulfur Lamp Chen Yuming et al.(3-33) The Influence of Illuminant/observe Condition on Color Measurement Che Xiaju Ma Yu Zhu Yin(4-4) Research on Power Supply and Light Source of Green Lighting Ma Weishan Zhou Wenjin Yang Shiguang(4-9) The Analyses for the Current Situation of Traffic Light in China Ning Chuwen Zhou Lijiao(4-15) Technical Present State and Prospects on Railway Color Signal Light of Our Country Sun Lifan(4-19) Energy Efficiency Standard, Labeling, Certification and Efficient Lighting Products Gao Fei Liu Hong(4-24) The Application of B-spline in the Design of Automobile Headlamp Zhou Jun Zhou Taiming(4-31) On Large Power Phosphor Electronic Ballast for Linear Fluorescent Lamps Deng Shuxing(4-36) Lighting Design and Application Lighting Landscape Features of Tiananmen Square Li Tienan Xiao Huiqian et al.(1-32) A Discussion of Urban Landscape Lighting in Chongqing He Ying Deng Shenjun et al.(1-36) A New Lighting Planning Method for Small Shop Interiors ——Merchandise Siting Method(Ⅰ) Cai Hongyi(1-41) A New Lighting Planning Method for Small Shop Interiors-Merchandise Siting Method(Ⅱ) Cai Hongyi(2-32) Light Environment in Housing Zhang Yaogen Zhang Shaogang Zheng Jianping(2-39) The Applications of Downlights in Interior Lighting Gu Yiyan Yu Lihua(2-45) Landscape Lighting Planning of Shengnan Avenue Li Tienan Zhu Ningtao(2-49) Lighting of Sports Hall and Auditorium Tadashi Nishimura(2-55) Prelude of New Century Illuminating Realum (2-60) Computer Simulation for the Daylighting Environments of Residential Buildings in Beijing Li Defu et al.(3-38) Primary Research of Classic Building Landscape Lighting Gao Guitai et al.(3-44) A Study on Glare Control in Gumnasium Lighting Luo Hong et al.(3

  17. Influence of presenilin 1 overexpression on endogenous tau phosphorylation in neuroblastoma cells%早老蛋白-1过度表达对神经母细胞瘤NG-108的tau蛋白磷酸化的影响

    Institute of Scientific and Technical Information of China (English)

    陈波; 程敏; 王寅; 孙凤艳; 朱粹青

    2006-01-01

    phorphorylated tau than the control cells. However, MTT test showed no significant difference between mock transfected cells and the wPS1 or mPS1 transfected cells. In addition, after transfection of the constructed PS1-EGFP vector, overexpressed EGFP-PS1 was located at cell surface membrane and subcellular organelles at earlier time at 12 hr, then EGFP-PS1 diffused in cytosol. Immunocytochemical observations demonstrated that some of the PS1-EGFP transfected cells contained more phosphorylated tau protein, which formed aggresome with PS-1-EGFP. When treated with phosphotase inhibitor okadaic acid, in the PS1-EGFP transfected cells accumulated more phosphorylated tau than the un-transfected cells. Conclusions Wild type PS1 is possibly involved in tauopathy in sporadic Alzheimer's disease.

  18. Determination of Two Diarrhetic Shellfish Poisons Residues in Mytilus edulis Linnaeus by High Performance Liquid Chromatography Tandem Mass Spectrometry%高效液相色谱-串联质谱法测定贻贝中腹泻性贝类毒素的含量

    Institute of Scientific and Technical Information of China (English)

    张海琪; 何欣; 郑重莺

    2012-01-01

    Establish the detection method of okadaic acid(OA) and dinophysistoxins(DTX-1) in Mytilus edulis using high performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS).Shellfish sample was extracted by 80% methyl.Shellfish extract solution was clean-up by Sep-pak silica column.A triple-quadrupole tandem mass spectrometer was used as a detector for HPLC to determine OA.As for the MS/MS,the multi-reactions monitoring(MRM) scan type and the negative ion electrospray ionization(-ESI) mode were applied.The precursor ion→product ion(m/z 803.5→m/z 255.1,m/z 803.5→m/z 563.1) was selected as OA quantitate detection ion pair.The precursor ion→product ion(m/z 817.4→m/z 255.1,m/z 817.4→m/z 113.1) was selected as DTX-1 quantitate detection ion pair.The mobile phase of HPLC was the methyl cyanide: 1% methanoic acid-water(vol/vol: 70:30) and the chromatographic column was Zorbax XDB-C18(2.1mm×150mm×5μm).The standard OA and DTX-1,the shellfish being added with OA and DTX-1,the shellfish sample were determine by the HPLC-MS/MS.The standard curve for OA showed good linearity over the concentration range of 5~640 ng/ml,the equation of linear regression was Y =207X-241(Q1/Q3:m/z 803.5→255.1),r was 0.9998,The recovery of sample being added with OA was 79.5%~88.6% and the RSD was 8.43%~10.4%.The standard curve for DTX-1 showed good linearity over the concentration range of 0 ~ 200 ng/ml,the equation of linear regression was Y =141X +3.59×103(Q1 /Q3: m / z817.4→255.1),r was 0.9997,The recovery of sample being added with DTX-1 was83.8%~91.2% and the RSD was 4.22%~6.54%.This HPLC-MS/MS is highly sensitive,fast,and very accurate.So it can be used for detecting the remain of OA and its natural derivative DTX-1 in shellfish.Among the 45 samples from the origin and market,4 samples were detected DSP,the ratio was 8.9%.%采用液相色谱-串联质谱法检测了贻贝中大田软

  19. Strong Coupling Gauge Theories in LHC ERA

    Science.gov (United States)

    Fukaya, H.; Harada, M.; Tanabashi, M.; Yamawaki, K.

    2011-01-01

    AdS/QCD, light-front holography, and the nonperturbative running coupling / Stanley J. Brodsky, Guy de Teramond and Alexandre Deur -- New results on non-abelian vortices - Further insights into monopole, vortex and confinement / K. Konishi -- Study on exotic hadrons at B-factories / Toru Iijima -- Cold compressed baryonic matter with hidden local symmetry and holography / Mannque Rho -- Aspects of baryons in holographic QCD / T. Sakai -- Nuclear force from string theory / K. Hashimoto -- Integrating out holographic QCD back to hidden local symmetry / Masayasu Harada, Shinya Matsuzaki and Koichi Yamawaki -- Holographic heavy quarks and the giant Polyakov loop / Gianluca Grignani, Joanna Karczmarek and Gordon W. Semenoff -- Effect of vector-axial-vector mixing to dilepton spectrum in hot and/or dense matter / Masayasu Harada and Chihiro Sasaki -- Infrared behavior of ghost and gluon propagators compatible with color confinement in Yang-Mills theory with the Gribov horizon / Kei-Ichi Kondo -- Chiral symmetry breaking on the lattice / Hidenori Fukaya [for JLQCD and TWQCD collaborations] -- Gauge-Higgs unification: Stable Higgs bosons as cold dark matter / Yutaka Hosotani -- The limits of custodial symmetry / R. Sekhar Chivukula ... [et al.] -- Higgs searches at the tevatron / Kazuhiro Yamamoto [for the CDF and D[symbol] collaborations] -- The top triangle moose / R. S. Chivukula ... [et al.] -- Conformal phase transition in QCD like theories and beyond / V. A. Miransky -- Gauge-Higgs unification at LHC / Nobuhito Maru and Nobuchika Okada -- W[symbol]W[symbol] scattering in Higgsless models: Identifying better effective theories / Alexander S. Belyaev ... [et al.] -- Holographic estimate of Muon g - 2 / Deog Ki Hong -- Gauge-Higgs dark matter / T. Yamashita -- Topological and curvature effects in a multi-fermion interaction model / T. Inagaki and M. Hayashi -- A model of soft mass generation / J. Hosek -- TeV physics and conformality / Thomas Appelquist -- Conformal

  20. Exogenous Brain-derived Neurotroplic Factor Decreases Cell Apoptosis by Depressing tau Protein Phosphorylation%外源性脑源性神经营养因子通过抑制tau蛋白磷酸化减少细胞凋亡

    Institute of Scientific and Technical Information of China (English)

    徐爱华; 孙永新; 商秀丽

    2013-01-01

    目的 观察外源性脑源性神经营养因子(BDNF)对tau蛋白过磷酸化及神经元凋亡的影响,探讨其可能的作用机制.方法 将培养的人神经母细胞瘤细胞(SH-SY5Y)分为正常对照组;冈田酸(OA)组:浓度为40 nmo/L的OA处理24 h;BDNF组:OA处理24 h后加入浓度为50 ng/mL的BDNF处理15 min;LY294002组:OA处理24 h后加入BDNF(50 ng/mL)及LY294002(40 nmol/L)共同处理15 min;K252a组:OA处理24 h后加入BDNF(50 ng/mL)及K252a (40 nmol/L)共同处理15 min.通过MTT检测细胞存活率、流式细胞仪检测细胞凋亡率、Western blot检测Ser199/202、pSer199/202及bcl-2表达.结果 MTT 实验显示OA组、LY294002组及K252a组细胞存活率较正常对照组及BDNF组明显减低(P<0.01);BDNF组与正常对照组无明显差异(P>0.05).流式细胞仪检测显示OA组、LY294002组及K252a组细胞凋亡率较正常对照组及BDNF组明显增加(P<0.01);BDNF组与正常对照组之间无统计学差异(P>0.05).Western blot显示OA组、LY294002组及K252a组pSer199/202表达较正常对照组及BDNF组明显增多(P<0.01),Ser199/202及bcl-2表达较对照组及BDNF组明显减少(P<0.01),BDNF组与正常对照组比较无统计学差异(P>0.05).结论 外源性BDNF可通过抑制tau蛋白磷酸化减少细胞凋亡.%Objective To observe the effects of exogenous brain-derived neurotrophic factor (BDNF) on tau protein phosphorylation and cell appoptosis,explore the relation between them and it's possible mechanism. Methods Culturaled SH-SY5Y cell was divided into the normal control group,okadaic acid (OA) group:treated with 40 nmol/L OA for 24 h;BDNF group:50 ng/m L BDNF was added after OA treated for 15min;K252a group:40 nmol/L K252a and 50 ng/mL BDNF was added after OA treated for 15 min;and LY294002 group:40 nmol/L LY294002 and 50 ng/mL BDNF was added after OA treated for 15 min. Through MTT to examin the cell survival rate;through flow cytometry to examin the cell appoptosis rate

  1. EDITORIAL: Non-polar and semipolar nitride semiconductors Non-polar and semipolar nitride semiconductors

    Science.gov (United States)

    Han, Jung; Kneissl, Michael

    2012-02-01

    topics including growth and heteroepitaxy, bulk GaN substrates, theory and modelling, optical properties, laser diodes and LEDs as well as transport properties and electronics. Farrell et al review materials and growth issues for high-performance non- and semipolar light-emitting devices, and Scholz provides an overview of heteroepitaxial growth of semipolar GaN. Okada et al review growth mechanisms of non- and semipolar GaN layers on patterned sapphire substrates, and Vennéguès discusses defect reduction methods for heteroepitaxially grown non- and semipolar III-nitride films. Leung et al explain how kinetic Wulff plots can be used to design and control non-polar and semipolar GaN heteroepitaxy, and a contribution by Sawaki et al explores the impurity incorporation in (1-101) GaN grown on Si substrates. In the area of bulk crystal growth Kucharski et al review non- and semipolar GaN substrates by ammonothermal growth, and Chichibu et al discuss the challenges for epitaxial growth of InGaN on free-standing m-plane GaN substrates. Calculation of semipolar orientations for wurtzitic semiconductor heterostructures and their application to nitrides and oxides are reviewed by Bigenwald et al, and Ito et al present an ab initio approach to reconstruction, adsorption, and incorporation on GaN surfaces. Finally, the theoretical description of non-polar and semipolar nitride semiconductor quantum-well structures is presented by Ahn et al. In a discussion of the optical properties, Kisin et al discuss the effect of the quantum well population on the optical characteristics of polar, semipolar and non-polar III-nitride light emitters, and Jönen et al investigate the indium incorporation and optical properties of non- and semipolar GaInN QW structures. Wernicke et al explore the emission wavelength of polar, non-polar, and semipolar InGaN quantum wells and the incorporation of indium. In a contribution by Melo et al, the gain in polar and non-polar/semipolar gallium

  2. Shallow Moho with aseismic upper crust and deep Moho with seismic lower crust beneath the Japanese Islands obtained by seismic tomography using data from dense seismic network

    Science.gov (United States)

    Matsubara, Makoto; Obara, Kazushige

    2015-04-01

    . The Moho discontinuity deepens over 35 km in the collision zone like as Kanto Mountains, the volcanic underplating zone as the Tohoku backbone range, and non-tension region like as Chugoku Mountains. These regions associated with deep Moho are characterized by the crustal seismicity within the depth range from 20 to 30 km. The iso-depth contour of 35 km beneath the southwestern Japan is consistent with that derived from the receiver function method (Shiomi et al. 2006). There are nonvolcanic tremors and short-time slow slip events (SSE) beneath the southwestern Japan (eg. Obara, 2002). Matsubara et al. (2009) consider that the tremors and SSEs occur along the contact zone of Moho discontinuity beneath the Eurasian plate and the subducting Philippine Sea plate beneath southwestern Japan. Our Moho model is consistent with this since they exist along the southern edge of the Moho discontinuity of the continental Eurasian plate. Reference: Hirata, N., Sakai, S., Nakagawa, S., Ishikawa, M., Sato, H., Kasahara, K., Kimura, H. and Honda, R. (2012) A new tomographic image on the Philippine Sea Slab beneath Tokyo - Implication to seismic hazard in the Tokyo metropolitan region, EOS, Transactions, AGU, T11C-06. Kita, S., T. Okada, A. Hasegawa, J. Nakajima, and T. Matsuzawa (2010) Anomalous deepening of a seismic belt in the upper-plane of the double seismic zone in the Pacific slab beneath the Hokkaido corner: Possible evidence for thermal shielding caused by subducted forearc crust materials, Earth Planet. Science Lett., 290, 415-426. Matsubara, M. and K. Obara (2011) The 2011 Off the Pacific Coast of Tohoku earthquake related to a strong velocity gradient with the Pacific plate, Earth Planets Space, 63, 663-667. Matsubara, M., K. Obara, and K. Kasahara (2009) High-Vp/Vs zone accompanying non-volcanic tremors and slow-slip events beneath southwestern Japan, Tectonophysics, 472, 6-17, doi:10.1016/j.tecto.2008.06.013. Obara, K. (2002) Nonvolcanic deep tremor associated with

  3. Study of rat neuronal genes with ordered differential display method

    Institute of Scientific and Technical Information of China (English)

    KANG; Jiansheng; (

    2001-01-01

    expression profiles in PC12 cells before and after nerve growth factor treatment, Proc. Natl. Acad. Sci. USA, 1995, 92: 8303-8307.[14]Tanaka, T., Kuwano, Y., Ishikawa, K. et al., Nucleotide sequence of cloned cDNA specific for rat ribosomal protein S11, J. Biol. Chem., 1985, 260(10): 6329-6333.[15]Muro, Y., Chan, E. K., Landberg, G. et al., A cell-cycle nuclear autoantigen containing WD-40 motifs expressed mainly in S and G2 phase cells, Biochem. Biophys. Res. Commun., 1995, 207(3): 1029-1037.[16]Ohshima, T., Kozak, C. A., Nagle, J. W. et al., Molecular cloning and chromosomal mapping of the mouse gene encoding cyclin-dependent kinase 5 regulatory subunit p35, Genomics, 1996, 35(2): 372-375.[17]Nada, S., Okada, M., MacAuley, A. et al., Cloning of a complementary DNA for a protein-tyrosine kinase that specifically phosphorylates a negative regulatory site of p60c-src, Nature, 1991, 351(6321): 69-72.[18]Watanabe, M., Isobe, T., Okuyama, T. et al., Molecular cloning of cdna to rat 14-3-3 eta chain polypeptide and the neuronal expression of the mRNA in the central nervous system, Brain Res. Mol. Brain Res., 1991, 10(2): 151-158.[19]Sampson, M. J., Lovell, R. S., Craigen, W. J., Isolation, characterization, and mapping of two mouse mitochondrial voltage-dependent anion channel isoforms, Genomics, 1996, 33(2): 283-288.[20]Schriner, J. E., Yi, W., Hofmann, S. L. et al., cDNA and genomic cloning of human palmitoyl-protein thioesterase (PPT), the enzyme defective in infantile neuronal ceroid lipofuscinosis, Genomics, 1996, 34(3): 317-322.[21]Azuma, T., Ao, S., Saito, Y. et al., Human SOX11, an upregulated gene during the neural differentiation, has a long 3' untranslated region, DNA Res., 1999, 6(5): 357-360.[22]Nishiyama, H., Higashitsuji, H., Yokoi, H. et al., Cloning and characterization of human CIRP (cold-inducible RNA-binding protein) cDNA and chromosomal assignment of the gene, Gene, 1997, 204(1-2): 115-120.[23]Ikeda, J., Kaneda, S

  4. Vlasov simulations of electron hole dynamics in inhomogeneous magnetic field

    Science.gov (United States)

    Kuzichev, Ilya; Vasko, Ivan; Agapitov, Oleksiy; Mozer, Forrest; Artemyev, Anton

    2017-04-01

    particular, our simulations suggest that slow EHs (which generation is usually attributed to the Buneman instability) can arise due to slowing down of fast EH generated by electron-beam instability. The estimate of the potential drop along EHs allow to estimate the parallel potential drop provided by EHs in a particular plasma system. 1. Matsumoto, H., H. Kojima, T. Miyatake, Y. Omura, M. Okada, I. Nagano, and M. Tsutsui, Electrotastic Solitary Waves (ESW) in the magnetotail: BEN wave forms observed by GEOTAIL, Geophys. Res. Lett., 21, 2915-2918, doi:10.1029/94GL01284, 1994. 2. Norgren, C., M. Andŕe, A. Vaivads, and Y. V. Khotyaintsev, Slow electron phase space holes: Magnetotail observations, Geophys. Res. Lett., 42, 1654-1661, doi:10.1002/2015GL063218, 2015. 3. Malaspina, D. M., J. R. Wygant, R. E. Ergun, G. D. Reeves, R. M. Skoug, and B. A. Larsen, Electric field structures and waves at plasma boundaries in the inner magnetosphere, Journal of Geophysical Research (Space Physics), 120, 4246-4263, doi:10.1002/2015JA021137, 2015. 4. Franz, J. R., P. M. Kintner, J. S. Pickett, and L.-J. Chen, Properties of small-amplitude electron phase-space holes observed by Polar, Journal of Geophysical Research (Space Physics), 110, A09212, doi:10.1029/2005JA011095, 2005. 5. Cattell, C., C. Neiman, J. Dombeck, J. Crumley, J. Wygant, C. A. Kletzing, W. K. Peterson, F. S. Mozer, and M. André (2003), Large amplitude solitary waves in and near the Earth's magnetosphere, magnetopause and bow shock: Polar and Cluster observations, Nonlinear Processes Geophys., 10, 13-26. 6. Mandrake, L., P. L. Pritchett, and F. V. Coroniti, Electron beam generated solitary structures in a nonuniform plasma system, Geophys. Res. Lett., 27, 2869-2872, doi:10.1029/2000GL003785, 2000. The work of I.K. was supported by Russian Foundation for Basic Research 16-32-00721 mol_a. The work of I.V., O.A. and F.M. was supported by JHU/APL contract 922613 (RBSPEFW).

  5. Geochemical study of boron isotopes in the process of loess weathering

    Institute of Scientific and Technical Information of China (English)

    ZHAO; Zhiqi; (

    2003-01-01

    ., Atmospheric carbon dioxide concentrations over the past 60 million years, Nature, 2000, 406: 695-699.[25]Liu Tungsheng, Loess and Environment (in Chinese), Beijing: Science Press, 1985, 191-302.[26]Gu Zhaoyan, Lal, D., Guo Zhengtang et al., 10Be geochemical characteristics of loess and redclay on the Loess Plateau, Quaternary Research (in Chinese), 2000, 20(5): 409-423.[27]Liu Tungsheng, Loess and Environment (in Chinese), Bejing: Science Pres, 1985, 1-481.[28]Zhao Zhiqi, Liu Congqiang, Xiao Yinkai, Separation of boron in acid-soluble phases in loess and paleosol deposits and its isotopic determination, Geochimica (in Chinese), 2000, 29(4): 351-357.[29]Xiao, Y. K., Beary, E. S., Fassett, J. D., An improved method for the high-precision isotopic measurement of boron by thermal ionization masses spectrometry, Int'l. J. Mass Spect. and Ion Proc., 1988, 85: 203-213.[30]Spivack, A. J., Edmond, J. M., Determination of boron isotope ratios by thermal ionization mass spectrometry of the dicesium metaborate cation, Anal. Chem., 1986, 58: 31-35.[31]Kiss, E., Ion-exchange separation and spectrophotometric determination of boron in geological materials, Anal. Chem. Acta, 1988, 211: 243-256.[32]Liu Tungsheng, Loess and Environment (in Chinese), Beijing: Science Press, 1985, 44-106.[33]Liu Congqiang, Zhao Zhiqi, Xiao Yinkai, Boron isotopic composition of loess and its implication for climatic tracing, Quaternary Research (in Chinese), 2000, 20(4): 394.[34]Taylor, S. R., Mclennan, S. M., Mcculloch, M. T., Geochemistry of loess, continental crustal composition and crustal model age, Geochim. Cosmochim. Acta, 1983, 47: 1897-1905.[35]Liu, C. Q., Masuda, A., Okada, A. et al., A geochemical study of loess and desert sand in northern China: Implications for continental crust weathering and composition, Chemical Geology, 1996, 106: 359-374.[36]Ishikawa, T., Nakamura, E., Boron isotope systematics of marine sediment, Earth Planet Sci. Lett., 1993, 117

  6. 25 years of pulsed laser deposition

    Science.gov (United States)

    Lorenz, Michael; Ramachandra Rao, M. S.

    2014-01-01

    -of-experiment schemes to shorten the optimization effort for new materials is presented at the end of this methodical section. Further, the issue contains original papers on other prominent PLD activities, such as dielectric SrTiO3 films, magnetic and spintronic La1-x Srx MnO3, and multiferroic BiFeO3. The role of cationic and anionic point defects and their control during PLD is discussed based on the examples of the simple perovskite SrMoO3 and the double perovskite Sr2CrWO6. The final paper in this thin-film-related section provides a good account of in situ high-temperature surface smoothing of Ba2TiSi2O8 fresnoite films and growth from glassy fresnoite targets with 100% theoretical density. The flexibility of the PLD technique has resulted in several schemes to grow nanostructures, which is unique in the nature of PLD. Okada's group succeeded in controlling the growth density of ZnO nanowires by varying the thickness of the ZnO buffer layer, and nanowalls could be patterned by interference phenomenon using laser irradiation. PLD-based methods are further used to grow metal nanoparticle plasmonic films with packing densities up to 1011 particles cm-2, and ZnO nanowires from screw dislocation driven two-dimensional hexagonal stacking on diamond substrates. Overall, this special issue provides an up-to-date overview on the current status, potential and the extraordinary success and development of PLD from a simple laboratory growth method to a viable industrial technique for fabrication of advanced oxide thin films. We thank all the authors and reviewers for their contributions to this special issue. We would like to place on record our gratitude for the timely help extended by the editorial team, Dr Olivia Roche, Dean Williams and Colin Adcock. References [1] Dijkkamp D, Venkatesan T, Wu X D, Shaheen S A, Jisrawi N, Min-Lee Y-H, McLean W L and Croft M 1987 Preparation of YBaCu oxide superconductor thin films using pulsed laser evaporation from high T c bulk material Appl. Phys. Lett

  7. The evidences of progressive pressurization of volcanic conduit as driving forces of unrest phenomena analyzed via modelling of multiplatform geodetic measurements: Fernandina (GALAPAGOS) and Maunaloa (HAWAII) case studies

    Science.gov (United States)

    Pepe, Susi; Castaldo, Raffaele; Casu, Francesco; D'Auria, Luca; De Luca, Claudio; De Novellis, Vincenzo; Solaro, Giuseppe; Tizzani, Pietro

    2017-04-01

    -12940. Okada, Y. Surface deformation due to shear and tensile faults in a half-space. Bull. Seism. Soc. Am. 75, 1135-1154 (1985). Sansosti, E., Berardino, P., Bonano, M., Calò, F., Castaldo, R., Casu, F., Manunta, M., Manzo, M., Pepe, A., Pepe, S., Solaro, G., Tizzani, P., Zeni, G., Lanari, R. (2014). How second generation SAR systems are impacting the analysis of ground deformation. International Journal of Applied Earth Observation and Geoinformation, 28, doi:10.1016/j.jag.2013.10.007. Tizzani, P., Battaglia, M., Zeni, G., Atzori, S., Berardino, P., Lanari, R. (2009). Uplift and magma intrusion at Long Valley caldera from InSAR and gravity measurements, Geology, January 2009 37; no.1; p. 63-66; doi:10.1130/G25318A.1 Tizzani, P., Battaglia, M., Castaldo, R., Pepe, A., Zeni, G., Lanari, R. (2015). Magma and fluid migration at Yellowstone Caldera in the last three decades inferred from InSAR, leveling, and gravity measurements. J. Geophys. Res. Solid Earth, 120, 2627-2647. doi: 10.1002/2014JB011502. Yang, X. M., Davis, P. M., and Dieterich, J. H. (1988), Deformation from inflation of a dipping finite prolate spheroid in an elastic half-space as a model for volcanic stressing. Journal of Geophysical Research: Solid Earth (1978-2012), 93(B5), 4249-4257.

  8. Extra-anatomic transplantations in autologous adult cell therapies aiding anatomical regeneration and physiological recovery – An insight and categorization

    Directory of Open Access Journals (Sweden)

    Editorial

    2015-12-01

    ;9(2:40-7. Ebisawa K, Kato R, Okada M, Kamei Y, Mazlyzam AL, Narita Y, Kagami H, Ueda M. Cell therapy for facial anti-aging. Med J Malaysia. 2008;63 Suppl A:41. The editorial team would like to acknowledge with gratitude the inputs from Dr. David W Green (Faculty of Dentistry, The University of Hong Kong & Department of Oral Biology, Yonsei University College of Dentistry, Seoul, Korea and Prof. J. Amalorpavanathan (Convenor, Transplant Authority of Tamil Nadu, India & Reader in Vascular Surgery, Madras Medical College, Chennai, India.

  9. 国外文献速报

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    ,Grakhov E L,Starostenkov M D.铝 中晶格间隙和特殊晶界的相互作用(英).Phys.Met.Metallogr.,1999,83(3):243~248 020115 Yin H,Koster J N.Ga-5%In 合金液凝固中浓度分层和固液界面形态的原位观察(英).J.Cryst.Growth,1999,205(4):590 ~606 020116 Regener D,Wagner I,Schick E.压铸镁合金AE42的 微观组织和力学性能(德).Giesserei Forsch,1999,51(4):154~160 020117 Wjoejead A J.Al-Ti-C型晶粒细化剂— —优点及应用(波).Przegl.Odlew.,2000,50(5):179~182 020118 Aikin J R M,Ramachandran G.挤压铸造A356和半固 态铸造A357铸件的力学性能(英).Die Cast Eng.,1999,43(6):44~57 020119 Evangelista E,Spigarelli S,Cabibbo M.触变成型 制造AZ91镁合金的高温蠕变反应(英).Synth.Lightweight Met.,1999(3):213~219 020120 Devos P,Rives B,Baziard Y.飞机用防腐蚀剂的附 着性和防蚀性的研究(法).Double Liaison-Phys.ChimieEcon Peint Adhes.,1999,(512):4 0~47 020121 相场 满.形状记忆合金的开发和在智能化构造中的 应用(日).日本机械学会年次大会讲演论文集,1999,1:740~741 020122 Schmid-Fetzer R,Pisch A,Grobner J.添加Sc处 理Al合金和Mg合金的计算热化学的应用(英).Mater.Sci.Eng.,A,2000,30(9):80~82 020123 Kawai H,Okada I,Tsuji I.冶金因素对失蜡铸造Co 基超合金力学性能的影响(日).J.High Temp.Soc.Jpn.,1999,25(6):287~294 020124 Goodwin F E.开发改良抗蠕变锌合金(英).Die Cast .Eng.,2000,44(4):32~35 020125 Mitterer C,Trentnjak W,Holler F.通过硬涂层提 高铝铸造用工具的疲劳寿命.Giesseriei,2000,87(3):57~61 020126 Kim M H,Jung C H,Jo H H.Ti和Sr对Ohno连铸工艺 生产Al-11.3%Si合金微观组织的影响(英).Metals and Mater.,20 00,6(3):235~240 020127 Kim S,Hong T,Kim H.失蜡铸造AZ91HP镁合金(英).M etals and Mater.,2000,6(3):275~279 020128 Ando T,Grant N J,Matsuc S.喷射成形AISI1020钢 的晶粒细化和稳定化(英).Mater.Sci.Eng.A,2000,288(1):34~41 020129 Niu Q