Sample records for nah oder fernwirkungstheorie

  1. The plant vacuolar Na+/H+ antiport.

    PubMed

    Barkla, B J; Apse, M P; Manolson, M F; Blumwald, E

    1994-01-01

    Salt stress imposes severe limitations on plant growth, however, the extent of growth reduction depends upon the soil salinity level and the plant species. One of the mechanisms employed by salt tolerant plants is the effective vacuolar compartmentalization of sodium. The sequestration of sodium into the vacuole occurs by the operation of a Na+/H+ antiport located at the tonoplast. Evidence for a plant vacuolar Na+/H+ antiport has been demonstrated in tissues, intact vacuoles and isolated tonoplast vesicles. In sugar beet cell suspensions, the activity of the vacuolar Na+/H+ antiport increased with increasing NaCl concentrations in the growth medium. This increased activity was correlated with the increased synthesis of a 170 kDa tonoplast polypeptide. In vivo labelling of tonoplast proteins showed the enhanced synthesis of the 170 kDa polypeptide not only upon exposure of the cells to salt, but also when the cells were grown in the presence of amiloride. Exposure of the cells to amiloride also resulted in increased vacuolar Na+/H+ antiport activity. Polyclonal antibodies raised against the 170 kDa polypeptide almost completely inhibited the antiport activity, suggesting the association of this protein with the plant vacuolar Na+/H+ antiport. Antibodies against the Na+/H+ antiport-associated polypeptide were used to screen a Beta lambda ZAP expression library. A partial clone of 1.65 kb was sequenced and found to encode a polypeptide with a putative transmembrane domain and a large hydrophilic C terminus. This clone showed no homology to any previously cloned gene at either the nucleic acid or the amino acid level.

  2. ATP Dependence of Na+/H+ Exchange

    PubMed Central

    Demaurex, Nicolas; Romanek, Robert R.; Orlowski, John; Grinstein, Sergio

    1997-01-01

    We studied the ATP dependence of NHE-1, the ubiquitous isoform of the Na+/H+ antiporter, using the whole-cell configuration of the patch-clamp technique to apply nucleotides intracellularly while measuring cytosolic pH (pHi) by microfluorimetry. Na+/H+ exchange activity was measured as the Na+-driven pHi recovery from an acid load, which was imposed via the patch pipette. In Chinese hamster ovary (CHO) fibroblasts stably transfected with NHE-1, omission of ATP from the pipette solution inhibited Na+/H+ exchange. Conversely, ATP perfusion restored exchange activity in cells that had been metabolically depleted by 2-deoxy-d-glucose and oligomycin. In cells dialyzed in the presence of ATP, no “run-down” was observed even after extended periods, suggesting that the nucleotide is the only diffusible factor required for optimal NHE-1 activity. Half-maximal activation of the antiporter was obtained at ∼5 mM Mg-ATP. Submillimolar concentrations failed to sustain Na+/H+ exchange even when an ATP regenerating system was included in the pipette solution. High ATP concentrations are also known to be required for the optimal function of other cation exchangers. In the case of the Na/Ca2+ exchanger, this requirement has been attributed to an aminophospholipid translocase, or “flippase.” The involvement of this enzyme in Na+/H+ exchange was examined using fluorescent phosphatidylserine, which is actively translocated by the flippase. ATP depletion decreased the transmembrane uptake of NBD-labeled phosphatidylserine (NBD-PS), indicating that the flippase was inhibited. Diamide, an agent reported to block the flippase, was as potent as ATP depletion in reducing NBD-PS uptake. However, diamide had no effect on Na+/H+ exchange, implying that the effect of ATP is not mediated by changes in lipid distribution across the plasma membrane. K-ATP and ATPγS were as efficient as Mg-ATP in sustaining NHE-1 activity, while AMP-PNP and AMP-PCP only partially substituted for ATP. In

  3. Effect of azathioprine on Na(+)/H(+) exchanger activity in dendritic cells.

    PubMed

    Bhandaru, Madhuri; Pasham, Venkanna; Yang, Wenting; Bobbala, Diwakar; Rotte, Anand; Lang, Florian

    2012-01-01

    Azathioprine is a powerful immunosuppressive drug, which is partially effective by interfering with the maturation and function of dendritic cells (DCs), antigen-presenting cells linking innate and adaptive immunity. DCs are stimulated by bacterial lipopolysaccharides (LPS), which trigger the formation of reactive oxygen species (ROS), paralleled by activation of the Na(+)/H(+) exchanger. The carrier is involved in the regulation of cytosolic pH, cell volume and migration. The present study explored whether azathioprine influences Na(+)/H(+) exchanger activity in DCs. DCs were isolated from murine bone marrow, cytosolic pH (pH(i)) was estimated utilizing 2',7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein (BCECF-AM) fluorescence, Na(+)/H(+) exchanger activity from the Na(+)-dependent realkalinization following an ammonium pulse, cell volume from forward scatter in FACS analysis, ROS production from 2',7'-dichlorodihydrofluorescein diacetate (DCFDA) fluorescence, TNFα release utilizing ELISA, and migration utilizing transwell migration assays. Exposure of DCs to lipopolysaccharide (LPS, 1 μg/ml) led to a transient increase of Na(+)/H(+) exchanger activity, an effect paralleled by ROS formation, increased cell volume, TNFα production and stimulated migration. Azathioprine (10 μM) did not significantly alter the Na(+)/H(+) exchanger activity, cell volume and ROS formation prior to LPS exposure but significantly blunted the LPS-induced stimulation of Na(+)/H(+) exchanger activity, ROS formation, cell swelling, TNFα production and cell migration. In conclusion, azathioprine interferes with the activation of dendritic cell Na(+)/H(+) exchanger by bacterial lipopolysaccharides, an effect likely participating in the anti-inflammatory action of the drug. Copyright © 2012 S. Karger AG, Basel.

  4. Na+/H+ exchange activity in the plasma membrane of Arabidopsis.

    PubMed

    Qiu, Quan-Sheng; Barkla, Bronwyn J; Vera-Estrella, Rosario; Zhu, Jian-Kang; Schumaker, Karen S

    2003-06-01

    In plants, Na+/H+ exchangers in the plasma membrane are critical for growth in high levels of salt, removing toxic Na+ from the cytoplasm by transport out of the cell. The molecular identity of a plasma membrane Na+/H+ exchanger in Arabidopsis (SOS1) has recently been determined. In this study, immunological analysis provided evidence that SOS1 localizes to the plasma membrane of leaves and roots. To characterize the transport activity of this protein, purified plasma membrane vesicles were isolated from leaves of Arabidopsis. Na+/H+ exchange activity, monitored as the ability of Na to dissipate an established pH gradient, was absent in plants grown without salt. However, exchange activity was induced when plants were grown in 250 mm NaCl and increased with prolonged salt exposure up to 8 d. H+-coupled exchange was specific for Na, because chloride salts of other monovalent cations did not dissipate the pH gradient. Na+/H+ exchange activity was dependent on Na (substrate) concentration, and kinetic analysis indicated that the affinity (apparent Km) of the transporter for Na+ is 22.8 mm. Data from two experimental approaches supports electroneutral exchange (one Na+ exchanged for one proton): (a) no change in membrane potential was measured during the exchange reaction, and (b) Na+/H+ exchange was unaffected by the presence or absence of a membrane potential. Results from this research provide a framework for future studies into the regulation of the plant plasma membrane Na+/H+ exchanger and its relative contribution to the maintenance of cellular Na+ homeostasis during plant growth in salt.

  5. [Nah-plasmids of IncP-9 group from natural strains of Pseudomonas].

    PubMed

    Levchuk, A A; Bulyga, I M; Izmalkova, T Iu; Sevast'ianovich, Ia R; Kosheleva, I A; Thomas, C M; Titok, M A

    2006-01-01

    Use of polymerase chain reaction helped to establish that the most frequent among naphthalene utilizing bacteria, isolated on the territory of Belarus, are Nah-plasmids of IncP-9 incompatibility group and those with indefinite systematic belonging. With the help of classical test of incompatibility, restriction and sequence analyses three new subgroups within the IncP-9 group were discovered (zeta, eta and IncP-9-like replicons). Conducting of restriction analysis for amplification products of nahG and nahAc genes allowed us to reveal, in addition to known sequences of stated determinants, two new types of nahG gene. Restriction analysis performed on amplification products of 16S RNA genes (ARDRA method) showed that native hosts of Nah-plasmids of IncP-9 group are not only fluorescent bacteria from genus Pseudomonas (P. fluorescens, P. putida, P. aeruginosa, P. species), but also non-fluorescent bacteria with indefinite specific belonging.

  6. Na+/H+ Exchange Activity in the Plasma Membrane of Arabidopsis1

    PubMed Central

    Qiu, Quan-Sheng; Barkla, Bronwyn J.; Vera-Estrella, Rosario; Zhu, Jian-Kang; Schumaker, Karen S.

    2003-01-01

    In plants, Na+/H+ exchangers in the plasma membrane are critical for growth in high levels of salt, removing toxic Na+ from the cytoplasm by transport out of the cell. The molecular identity of a plasma membrane Na+/H+ exchanger in Arabidopsis (SOS1) has recently been determined. In this study, immunological analysis provided evidence that SOS1 localizes to the plasma membrane of leaves and roots. To characterize the transport activity of this protein, purified plasma membrane vesicles were isolated from leaves of Arabidopsis. Na+/H+ exchange activity, monitored as the ability of Na to dissipate an established pH gradient, was absent in plants grown without salt. However, exchange activity was induced when plants were grown in 250 mm NaCl and increased with prolonged salt exposure up to 8 d. H+-coupled exchange was specific for Na, because chloride salts of other monovalent cations did not dissipate the pH gradient. Na+/H+ exchange activity was dependent on Na (substrate) concentration, and kinetic analysis indicated that the affinity (apparent Km) of the transporter for Na+ is 22.8 mm. Data from two experimental approaches supports electroneutral exchange (one Na+ exchanged for one proton): (a) no change in membrane potential was measured during the exchange reaction, and (b) Na+/H+ exchange was unaffected by the presence or absence of a membrane potential. Results from this research provide a framework for future studies into the regulation of the plant plasma membrane Na+/H+ exchanger and its relative contribution to the maintenance of cellular Na+ homeostasis during plant growth in salt. PMID:12805632

  7. Na+/H+ antiport is essential for Yersinia pestis virulence.

    PubMed

    Minato, Yusuke; Ghosh, Amit; Faulkner, Wyatt J; Lind, Erin J; Schesser Bartra, Sara; Plano, Gregory V; Jarrett, Clayton O; Hinnebusch, B Joseph; Winogrodzki, Judith; Dibrov, Pavel; Häse, Claudia C

    2013-09-01

    Na(+)/H(+) antiporters are ubiquitous membrane proteins that play a central role in the ion homeostasis of cells. In this study, we examined the possible role of Na(+)/H(+) antiport in Yersinia pestis virulence and found that Y. pestis strains lacking the major Na(+)/H(+) antiporters, NhaA and NhaB, are completely attenuated in an in vivo model of plague. The Y. pestis derivative strain lacking the nhaA and nhaB genes showed markedly decreased survival in blood and blood serum ex vivo. Complementation of either nhaA or nhaB in trans restored the survival of the Y. pestis nhaA nhaB double deletion mutant in blood. The nhaA nhaB double deletion mutant also showed inhibited growth in an artificial serum medium, Opti-MEM, and a rich LB-based medium with Na(+) levels and pH values similar to those for blood. Taken together, these data strongly suggest that intact Na(+)/H(+) antiport is indispensable for the survival of Y. pestis in the bloodstreams of infected animals and thus might be regarded as a promising noncanonical drug target for infections caused by Y. pestis and possibly for those caused by other blood-borne bacterial pathogens.

  8. Silicon dynamics in the Oder estuary, Baltic Sea

    NASA Astrophysics Data System (ADS)

    Pastuszak, Marianna; Conley, Daniel J.; Humborg, Christoph; Witek, Zbigniew; Sitek, Stanisław

    2008-10-01

    Studies on dissolved silicate (DSi) and biogenic silica (BSi) dynamics were carried out in the Oder estuary, Baltic Sea in 2000-2005. The Oder estuary proved to be an important component of the Oder River-Baltic Sea continuum where very intensive seasonal DSi uptake during spring and autumn, but also BSi regeneration during summer take place. Owing to the regeneration process annual DSi patterns in the river and the estuary distinctly differed; the annual patterns of DSi in the estuary showed two maxima and two minima in contrast to one maximum- and one minimum-pattern in the Oder River. DSi concentrations in the river and in the estuary were highest in winter (200-250 μmol dm - 3 ) and lowest (often less than 1 μmol dm - 3 ) in spring, concomitant with diatom growth; such low values are known to be limiting for new diatom growth. Secondary DSi summer peaks at the estuary exit exceeded 100 μmol dm - 3 , and these maxima were followed by autumn minima coinciding with the autumn diatom bloom. Seasonal peaks in BSi concentrations (ca. 100 μmol dm - 3 ) occurred during the spring diatom bloom in the Oder River. Mass balance calculations of DSi and BSi showed that DSi + BSi import to the estuary over a two year period was 103.2 kt and that can be compared with the DSi export of 98.5 kt. The difference between these numbers gives room for ca. 2.5 kt BSi to be annually exported to the Baltic Sea. Sediment cores studies point to BSi annual accumulation on the level of 2.5 kt BSi. BSi import to the estuary is on the level of ca. 10.5 kt, thus ca. 5 kt of BSi is annually converted into the DSi, increasing the pool of DSi that leaves the system. BSi concentrations being ca. 2 times higher at the estuary entrance than at its exit remain in a good agreement with the DSi and BSi budgeting presented in the paper.

  9. The mechanisms of brush border Na+/H+ exchanger activation by corticosteroids.

    PubMed

    Zallocchi, Marisa; Igarreta, Pilar; Calvo, Juan Carlos; Reboucas, Nancy Amaral; Damasco, María Christina

    2003-02-01

    Previously we showed that corticosterone and aldosterone increased proton fluxes in proximal tubule, by micropuncture and stationary microperfusion. Since the Na+/H+ exchanger is responsible for the main proximal proton secretion, we have now evaluated the effects aldosterone on Na+/H+ exchange activity in brush border vesicles. In order to evaluate the mechanism of action of glucocorticoids and mineralocorticoids, we studied the comparative effects of corticosterone and aldosterone on the abundance of NHE3 and NHE2 isoforms. We isolated renal brush border vesicles from rats by differential centrifugation in sham-operated, adrenalectomized, and adrenalectomized-aldosterone treated (ADX + aldosterone) animals. We measured the kinetics of H+ transport in response to increasing concentrations of Sodium Gluconate by fluorimetry using acridine orange. For Na+/H+ exchanger abundance we used Western blot analysis of brush border proteins in the above groups and in adrenalectomized-corticosterone treated rats. The Vmax in adrenalectomized animals was 22,162+/-1828 fluorescence units/min; in sham animals, 37,020+/-2722; and in ADX + aldosterone, 42,344+/-3044 (p<0.01 adrenalectomized vs others). No differences in Km were observed. Adrenalectomy decreased NHE3 abundance over Sham by 32% without modifying NHE2. Corticosterone-replacement enhanced NHE3 abundance by 76% and failed to increase NHE2. Aldosterone enhanced NHE2 abundance by 75% and did not increase NHE3. Mineralocorticoids enhance Na+/H+ exchange activity by increasing NHE2 abundance; glucocorticoids, by increasing NHE3 abundance.

  10. Role of the Na+/H+ antiporter in rat proximal tubule bicarbonate absorption.

    PubMed Central

    Preisig, P A; Ives, H E; Cragoe, E J; Alpern, R J; Rector, F C

    1987-01-01

    Amiloride and the more potent amiloride analog, 5-(N-t-butyl) amiloride (t-butylamiloride), were used to examine the role of the Na+/H+ antiporter in bicarbonate absorption in the in vivo microperfused rat proximal convoluted tubule. Bicarbonate absorption was inhibited 29, 46, and 47% by 0.9 mM or 4.3 mM amiloride, or 1 mM t-butylamiloride, respectively. Sensitivity of the Na+/H+ antiporter to these compounds in vivo was examined using fluorescent measurements of intracellular pH with (2', 7')-bis(carboxyethyl)-(5,6)-carboxyfluorescein (BCECF). Amiloride and t-butylamiloride were shown to be as potent against the antiporter in vivo as in brush border membrane vesicles. A model of proximal tubule bicarbonate absorption was used to correct for changes in the luminal profiles for pH and inhibitor concentration, and for changes in luminal flow rate in the various series. We conclude that the majority of apical membrane proton secretion involved in transepithelial bicarbonate absorption is mediated by the Na+-dependent, amiloride-sensitive Na+H+ antiporter. However, a second mechanism of proton secretion contributes significantly to bicarbonate absorption. This mechanism is Na+-independent and amiloride-insensitive. PMID:2888788

  11. Structural and Kinetic Properties of the Aldehyde Dehydrogenase NahF, a Broad Substrate Specificity Enzyme for Aldehyde Oxidation.

    PubMed

    Coitinho, Juliana B; Pereira, Mozart S; Costa, Débora M A; Guimarães, Samuel L; Araújo, Simara S; Hengge, Alvan C; Brandão, Tiago A S; Nagem, Ronaldo A P

    2016-09-27

    The salicylaldehyde dehydrogenase (NahF) catalyzes the oxidation of salicylaldehyde to salicylate using NAD(+) as a cofactor, the last reaction of the upper degradation pathway of naphthalene in Pseudomonas putida G7. The naphthalene is an abundant and toxic compound in oil and has been used as a model for bioremediation studies. The steady-state kinetic parameters for oxidation of aliphatic or aromatic aldehydes catalyzed by 6xHis-NahF are presented. The 6xHis-NahF catalyzes the oxidation of aromatic aldehydes with large kcat/Km values close to 10(6) M(-1) s(-1). The active site of NahF is highly hydrophobic, and the enzyme shows higher specificity for less polar substrates than for polar substrates, e.g., acetaldehyde. The enzyme shows α/β folding with three well-defined domains: the oligomerization domain, which is responsible for the interlacement between the two monomers; the Rossmann-like fold domain, essential for nucleotide binding; and the catalytic domain. A salicylaldehyde molecule was observed in a deep pocket in the crystal structure of NahF where the catalytic C284 and E250 are present. Moreover, the residues G150, R157, W96, F99, F274, F279, and Y446 were thought to be important for catalysis and specificity for aromatic aldehydes. Understanding the molecular features responsible for NahF activity allows for comparisons with other aldehyde dehydrogenases and, together with structural information, provides the information needed for future mutational studies aimed to enhance its stability and specificity and further its use in biotechnological processes.

  12. NaHS Protects against the Impairments Induced by Oxygen-Glucose Deprivation in Different Ages of Primary Hippocampal Neurons

    PubMed Central

    Yu, Qian; Wang, Binrong; Zhao, Tianzhi; Zhang, Xiangnan; Tao, Lei; Shi, Jinshan; Sun, Xude; Ding, Qian

    2017-01-01

    Brain ischemia leads to poor oxygen supply, and is one of the leading causes of brain damage and/or death. Neuroprotective agents are thus in great need for treatment purpose. Using both young and aged primary cultured hippocampal neurons as in vitro models, we investigated the effect of sodium hydrosulfide (NaHS), an exogenous donor of hydrogen sulfide, on oxygen-glucose deprivation (OGD) damaged neurons that mimick focal cerebral ischemia/reperfusion (I/R) induced brain injury. NaHS treatment (250 μM) protected both young and aged hippocampal neurons, as indicated by restoring number of primary dendrites by 43.9 and 68.7%, number of dendritic end tips by 59.8 and 101.1%, neurite length by 36.8 and 66.7%, and spine density by 38.0 and 58.5% in the OGD-damaged young and aged neurons, respectively. NaHS treatment inhibited growth-associated protein 43 downregulation, oxidative stress in both young and aged hippocampal neurons following OGD damage. Further studies revealed that NaHS treatment could restore ERK1/2 activation, which was inhibited by OGD-induced protein phosphatase 2 (PP2A) upregulation. Our results demonstrated that NaHS has potent protective effects against neuron injury induced by OGD in both young and aged hippocampal neurons. PMID:28326019

  13. Calcineurin homologous protein as an essential cofactor for Na+/H+ exchangers.

    PubMed

    Pang, T; Su, X; Wakabayashi, S; Shigekawa, M

    2001-05-18

    The Na+/H+ exchangers (NHEs) comprise a family of transporters that catalyze cell functions such as regulation of the pH and volume of a cell and epithelial absorption of Na+ and bicarbonate. Ubiquitous calcineurin B homologous protein (CHP or p22) is co-localized and co-immunoprecipitated with expressed NHE1, NHE2, or NHE3 independently of its myristoylation and Ca2+ binding, and its binding site was identified as the juxtamembrane region within the carboxyl-terminal cytoplasmic domain of exchangers. CHP binding-defective mutations of NHE1-3 or CHP depletion by injection of the competitive CHP-binding region of NHE1 into Xenopus oocytes resulted in a dramatic reduction (>90%) in the Na+/H+ exchange activity. The data suggest that CHP serves as an essential cofactor, which supports the physiological activity of NHE family members.

  14. Identification of a 170-kDa protein associated with the vacuolar Na+/H+ antiport of Beta vulgaris.

    PubMed Central

    Barkla, B J; Blumwald, E

    1991-01-01

    The effect of the addition of amiloride to the growth medium was tested on the Na+/H+ antiport activity of tonoplast vesicles isolated from sugar beet (beta vulgaris L.) cell suspensions. Cells grown in the presence of NaCl and amiloride displayed an increased antiport activity. Analysis of the kinetic data showed that while the affinity of the antiport for Na+ ions did not change, the maximal velocity of the Na+/H+ exchange increased markedly. These results suggest the addition of more antiport molecules to the tonoplast and/or an increase in the turnover rate of the Na+/H+ exchange. The increase in activity of the antiport by the presence of amiloride was correlated with the enhanced synthesis of a tonoplast 170-kDa polypeptide. The increased synthesis of this polypeptide was detected not only upon exposure of the cells to amiloride but also when the cells were exposed to high NaCl concentrations. Polyclonal antibodies against the 170-kDa polypeptide almost completely inhibited the antiport activity. These results suggest the association of the 170-kDa polypeptide with the vacuolar Na+/H+ antiport. Images PMID:1662387

  15. Identification of a 170-kDa protein associated with the vacuolar Na+/H+ antiport of Beta vulgaris.

    PubMed

    Barkla, B J; Blumwald, E

    1991-12-15

    The effect of the addition of amiloride to the growth medium was tested on the Na+/H+ antiport activity of tonoplast vesicles isolated from sugar beet (beta vulgaris L.) cell suspensions. Cells grown in the presence of NaCl and amiloride displayed an increased antiport activity. Analysis of the kinetic data showed that while the affinity of the antiport for Na+ ions did not change, the maximal velocity of the Na+/H+ exchange increased markedly. These results suggest the addition of more antiport molecules to the tonoplast and/or an increase in the turnover rate of the Na+/H+ exchange. The increase in activity of the antiport by the presence of amiloride was correlated with the enhanced synthesis of a tonoplast 170-kDa polypeptide. The increased synthesis of this polypeptide was detected not only upon exposure of the cells to amiloride but also when the cells were exposed to high NaCl concentrations. Polyclonal antibodies against the 170-kDa polypeptide almost completely inhibited the antiport activity. These results suggest the association of the 170-kDa polypeptide with the vacuolar Na+/H+ antiport.

  16. Jak2 and Ca2+/calmodulin are key intermediates for bradykinin B2 receptor-mediated activation of Na+/H+ exchange in KNRK and CHO cells.

    PubMed

    Lefler, David; Mukhin, Yurii V; Pettus, Tobiah; Leeb-Lundberg, L M Fredrik; Garnovskaya, Maria N; Raymond, John R

    2003-04-01

    Na(+)/H(+) exchangers are ubiquitous in mammalian cells, carrying out key functions, such as cell volume defense, acid-base homeostasis, and regulation of the cytoskeleton. We used two screening technologies (FLIPR and microphysiometry) to characterize the signal transduction pathway used by the bradykinin B(2) receptor to activate Na(+)/H(+) exchange in two cell lines, KNRK and CHO. In both cell types, B(2) receptor activation resulted in rapid increases in the rate of proton extrusion that were sodium-dependent and could be blocked by the Na(+)/H(+) exchange inhibitors EIPA and MIA or by replacing extracellular sodium with TMA. Activation of Na(+)/H(+) exchange by bradykinin was concentration-dependent and could be blocked by the selective B(2) receptor antagonist HOE140, but not by the B(1) receptor antagonist des-Arg10-HOE140. Inhibitors of Jak2 tyrosine kinase (genistein and AG490) and of CAM (W-7 and calmidazolium) attenuated bradykinin-induced activation of Na(+)/H(+) exchange. Bradykinin induced formation of a complex between CAM and Jak2, supporting a regulatory role for Jak2 and CAM in the activation of Na(+)/H(+) exchange in KNRK and CHO cells. We propose that this pathway (B(2) receptor --> Jak2 --> CAM --> Na(+)/H(+) exchanger) is a fundamental regulator of Na(+)/H(+) exchange activity.

  17. Salicylate and catechol levels are maintained in nahG transgenic poplar

    Treesearch

    Alison M. Morse; Timothy J. Tschaplinski; Christopher Dervinis; Paula M. Pijut; Eric A. Schmelz; Wendy Day; John M. Davis

    2007-01-01

    Metabolic profiling was used to investigate the molecular phenotypes of a transgenic Populus tremula × P. alba hybrid expressing the nahG transgene, a bacterial gene encoding salicylate hydroxylase that converts salicylic acid to catechol. Despite the efficacy of this transgenic approach to reduce...

  18. Observation of double-well potential of NaH C 1Σ+ state: Deriving the dissociation energy of its ground state

    NASA Astrophysics Data System (ADS)

    Chu, Chia-Ching; Huang, Hsien-Yu; Whang, Thou-Jen; Tsai, Chin-Chun

    2018-03-01

    Vibrational levels (v = 6-42) of the NaH C 1Σ+ state including the inner and outer wells and the near-dissociation region were observed by pulsed optical-optical double resonance fluorescence depletion spectroscopy. The absolute vibrational quantum number is identified by comparing the vibrational energy difference of this experiment with the ab initio calculations. The outer well with v up to 34 is analyzed using the Dunham expansion and a Rydberg-Klein-Rees (RKR) potential energy curve is constructed. A hybrid double-well potential combined with the RKR potential, the ab initio calculation, and a long-range potential is able to describe the whole NaH C 1Σ+ state including the higher vibrational levels (v = 35-42). The dissociation energy of the NaH C 1Σ+ state is determined to be De(C) = 6595.10 ± 5 cm-1 and then the dissociation energy of the NaH ground state De(X) = 15 807.87 ± 5 cm-1 can be derived.

  19. Tanzendes Tier oder exzentrische Positionalität - Philosophische Anthropologie zwischen Darwinismus und Kulturalismus

    NASA Astrophysics Data System (ADS)

    Fischer, Joachim

    Zunächst kurz vorweg zu den Formeln im Titel: "exzentrische Positionalität“ ist der Kategorienvorschlag der Philosophischen Anthropologie (genauer: von Helmuth Plessner) für den Menschen, für seine "Sonderstellung“ unter den Lebewesen - ich werde diesen Begriff erläutern. So viel kann man sagen: Der Terminus ist nicht schwieriger als "Transzendentalität“ oder das "Apriori“ oder "Autopoiesis“, also Begriffe, mit deren Orientierungswert in der intellektuellen Öffentlichkeit bereits gespielt wird, bietet aber möglicherweise mehr Erschließungskraft als die Kunstbegriffe z. B. von Kant, Maturana oder Luhmann. Und "tanzendes Tier“ ist ein glücklicher Anschauungsbegriff, eine Art Übersetzung für "exzentrische Positionalität“ - also ein "verrücktes“ Lebewesen, eine Verrückung im evolutionären Leben, die dieses Lebewesen von Natur aus zu einer bestimmten Art von Lebensführung, nämlich Kultur nötigt. Die Absicht des Beitrages ist es, die Philosophische Anthropologie als eine spezifische Theorietechnik zu präsentieren, um einen adäquaten Begriff des Menschen zu erreichen, und zwar eine Theoriestrategie angesichts des cartesianischen Dualismus - also des Dualismus zwischen Naturalismus und Kulturalismus.

  20. Contribution of the amiloride-sensitive component and the Na+/H+ exchanger to renal responsiveness to vasoconstrictors.

    PubMed

    Vargas, Pablo; Wangensteen, Rosemary; Rodríguez-Gómez, Isabel; Perez-Abud, Rocío; Osuna, Antonio; Quesada, Andrés; Vargas, Félix

    2011-01-01

    This study analyzed the role of the amiloride-sensitive component and the participation of the Na(+)/H(+) exchanger in renal responsiveness to vasoconstrictors in the isolated perfused rat kidney. The renal responses to vasoconstrictors (angiotensin II, phenylephrine, vasopressin and KCl) were studied under baseline conditions and after the administration of amiloride (10 and 100 μmol/l) or the specific Na(+)/H(+) exchange inhibitor ethylisopropylamiloride (EIPA, 10 μmol/l). The effects of amiloride and EIPA on renal responsiveness to vasoconstrictors were also analyzed in endothelium-denuded preparations. Amiloride reduced renal responsiveness to all vasoconstrictors in a dose-related manner, whereas EIPA did not affect the renal pressor response to KCl. The inhibitory effects of amiloride and EIPA on renal responsiveness to vasoconstrictors persisted after endothelium removal. These results indicate that the amiloride-sensitive component and the Na(+)/H(+) exchanger play an important role in responsiveness to the main endogenous vasoconstrictors in the renal vasculature. These results also suggest that amiloride might be useful as an inhibitor of renal vasoconstriction, even in diseases with endothelial dysfunction. Copyright © 2011 S. Karger AG, Basel.

  1. Effects of electron doping on the stability of the metal hydride NaH

    NASA Astrophysics Data System (ADS)

    Olea-Amezcua, M. A.; Rivas-Silva, J. F.; de la Peña-Seaman, O.; Heid, R.; Bohnen, K. P.

    2017-04-01

    Alkali and alkali-earth metal hydrides have high volumetric and gravimetric hydrogen densities, but due to their high thermodynamic stability, they possess high dehydrogenation temperatures which may be reduced by transforming these compounds into less stable states/configurations. We present a systematic computational study of the electron doping effects on the stability of the alkali metal hydride NaH substituted with Mg, using the self-consistent version of the virtual crystal approximation to model the alloy Na1-x Mg x H. The phonon dispersions were studied paying special attention to the crystal stability and the correlations with the electronic structure taking into account the zero point energy contribution. We found that substitution of Na by Mg in the hydride invokes a reduction of the frequencies, leading to dynamical instabilities for Mg content of 25%. The microscopic origin of these instabilities could be related to the formation of ellipsoidal Fermi surfaces centered at the L point due to the metallization of the hydride by the Mg substitution. Applying the quasiharmonic approximation, thermodynamic properties like heat capacities, vibrational entropies and vibrational free energies as a function of temperature at zero pressure are obtained. These properties determine an upper temperature for the thermodynamic stability of the hydride, which decreases from 600 K for NaH to 300 K at 20% Mg concentration. This significant reduction of the stability range indicates that dehydrogenation could be favoured by electron doping of NaH.

  2. Response of Polish rivers (Vistula, Oder) to reduced pressure from point sources and agriculture during the transition period (1988-2008)

    NASA Astrophysics Data System (ADS)

    Pastuszak, Marianna; Stålnacke, Per; Pawlikowski, Krzysztof; Witek, Zbigniew

    2012-06-01

    The Vistula and Oder Rivers, two out of the seven largest rivers in the Baltic drainage basin, were responsible for 25% of total riverine nitrogen (TN) and 37% of total riverine phosphorus (TP) input to the Baltic Sea in 2000. The aim of this paper is to evaluate the response of these two rivers to changes that took place in Polish economy during the transition period (1988-2008). The economic changes encompassed: construction of nearly 900 waste water treatment plants in 1999-2008, modernization or closure of obsolete factories, economizing in water consumption, closure or change of ownership of State-owned farms, a drop in fertilizer application, and a decline in livestock stocking. More intensive agriculture and higher point source emissions in the Oder than in the Vistula basin resulted in higher concentrations of TN, nitrate (NO3-N), and TP in the Oder waters in the entire period of our studies. In both rivers, nutrient concentrations and loads showed significant declining trends in the period 1988-2008. TN loads decreased by ca. 20% and 25% in the Vistula and Oder; TP loads dropped by ca. 15% and 65% in the Vistula and Oder. The reduction in phosphorus loads was particularly pronounced in the Oder basin, which was characterized by efficient management systems aiming at mitigation of nutrient emission from the point sources and greater extent of structural changes in agricultural sector during the transition period. The trends in riverine loads are discussed in the paper in relation to socio-economical changes during the transition period, and with respect to physiographic features.

  3. H(+)/solute-induced intracellular acidification leads to selective activation of apical Na(+)/H(+) exchange in human intestinal epithelial cells.

    PubMed

    Thwaites, D T; Ford, D; Glanville, M; Simmons, N L

    1999-09-01

    The intestinal absorption of many nutrients and drug molecules is mediated by ion-driven transport mechanisms in the intestinal enterocyte plasma membrane. Clearly, the establishment and maintenance of the driving forces - transepithelial ion gradients - are vital for maximum nutrient absorption. The purpose of this study was to determine the nature of intracellular pH (pH(i)) regulation in response to H(+)-coupled transport at the apical membrane of human intestinal epithelial Caco-2 cells. Using isoform-specific primers, mRNA transcripts of the Na(+)/H(+) exchangers NHE1, NHE2, and NHE3 were detected by RT-PCR, and identities were confirmed by sequencing. The functional profile of Na(+)/H(+) exchange was determined by a combination of pH(i), (22)Na(+) influx, and EIPA inhibition experiments. Functional NHE1 and NHE3 activities were identified at the basolateral and apical membranes, respectively. H(+)/solute-induced acidification (using glycylsarcosine or beta-alanine) led to Na(+)-dependent, EIPA-inhibitable pH(i) recovery or EIPA-inhibitable (22)Na(+) influx at the apical membrane only. Selective activation of apical (but not basolateral) Na(+)/H(+) exchange by H(+)/solute cotransport demonstrates that coordinated activity of H(+)/solute symport with apical Na(+)/H(+) exchange optimizes the efficient absorption of nutrients and Na(+), while maintaining pH(i) and the ion gradients involved in driving transport.

  4. Proximal bicarbonate absorption independent of Na+-H+ exchange: effect of bicarbonate load.

    PubMed

    Bank, N; Aynedjian, H S; Mutz, B F

    1989-04-01

    To study proximal tubule bicarbonate absorption that is not due to the neutral Na+-H+ antiporter, mid to late proximal convolutions of the rat kidney were microperfused in vivo with a sodium-free choline solution containing 10(-3) M amiloride. The average sodium concentration resulting from sodium influx was 12 mM. At such low intraluminal [Na+], 10(-3) M amiloride should have inhibited the Na+-H+ antiporter by greater than 95%. When 25 mM HCO3- was in the perfusion fluid, measured total CO2 absorption was 100 pmol.mm-1.min-1. When luminal [HCO3-] was raised to 50 mM, and blood [HCO3-] was also raised to approximately 50 mM to avoid a transepithelial HCO3- concentration gradient, total CO2 absorption increased to greater than 300 pmol.mm-1.min-1. Thus raising intraluminal HCO3- concentration caused a marked increase in total CO2 absorption even though intraluminal [Na+] was low and amiloride was present. Control perfusions containing 140 mM Na+ yielded total CO2 absorption that was approximately 100 pmol.mm-1.min-1 higher than with the respective sodium-free perfusion solutions. In additional experiments, either DCCD or NEM was added to sodium-free perfusion solutions to inhibit H+-ATPase. These inhibitors reduced Na+-H+ independent total CO2 absorption markedly. Our observations suggest that under physiological acid-base conditions, sodium-independent H+ secretion can account for approximately 50% of total HCO3- absorption in mid to late proximal convolutions. This mechanism is stimulated by an increase in ambient HCO(-3) concentration to a degree that might account for the load-dependency of proximal HCO(-3) absorption in these segments of the proximal tubule.(ABSTRACT TRUNCATED AT 250 WORDS)

  5. Restoration of normal pH triggers ischemia-reperfusion injury in lung by Na+/H+ exchange activation.

    PubMed

    Moore, T M; Khimenko, P L; Taylor, A E

    1995-10-01

    The effects of acidotic extracellular pH and Na+/H+ exchange inhibition on ischemia-reperfusion (I/R)-induced microvascular injury were studied in the isolated, buffer-perfused rat lung. When lungs were subjected to 45 min of ischemia followed by 30 min of reperfusion, the capillary filtration coefficient (Kfc) increased significantly, resulting in a change in Kfc (delta Kfc) of 0.360 +/- 0.09 ml.min-1.cmH2O-1.100 g-1. Addition of hydrochloric acid to the perfusate before ischemia at a concentration sufficient to reduce perfusate pH from 7.38 +/- 0.03 to 7.09 +/- 0.04 completely prevented the increase in Kfc associated with I/R (delta Kfc = 0.014 +/- 0.034 ml.min-1.cmH2O-1.100 g-1). Addition of a Na+/H+ exchange inhibitor, 5-(N,N-dimethyl)-amiloride, to the perfusate either before ischemia or at reperfusion also prevented the I/R-induced permeability increase (delta Kfc = 0.01 +/- 0.02 and -0.001 +/- 0.02 ml.min-1.cmH2O-1.100 g-1, respectively). We conclude that restoration of flow at physiological pH to the postischemic lung activates the Na+/H+ exchange system, which may represent the "triggering mechanism" responsible for initiating reperfusion-induced microvascular injury.

  6. Hydrogen sulfide from a NaHS source attenuates dextran sulfate sodium (DSS)-induced inflammation via inhibiting nuclear factor-κB

    PubMed Central

    Chen, Xi; Liu, Xi-shuang

    2016-01-01

    This study investigated the alleviating effects of hydrogen sulfide (H2S), derived from sodium hydrosulfide (NaHS), on inflammation induced by dextran sulfate sodium (DSS) in both in vivo and in vitro models. We found that NaHS injection markedly decreased rectal bleeding, diarrhea, and histological injury in DSS-challenged mice. NaHS (20 μmol/L) reversed DSS-induced inhibition in cell viability in Caco-2 cells and alleviated pro-inflammation cytokine expression in vivo and in vitro, indicating an anti-inflammatory function for H2S. It was also found that H2S may regulate cytokine expression by inhibiting the nuclear factor-κB (NF-κB) signaling pathway. In conclusion, our results demonstrated that H2S alleviated DSS-induced inflammation in vivo and in vitro and that the signal mechanism might be associated with the NF-κB signaling pathway. PMID:26984841

  7. Response of bacterial pdo1, nah, and C12O genes to aged soil PAH pollution in a coke factory area.

    PubMed

    Han, Xue-Mei; Liu, Yu-Rong; Zheng, Yuan-Ming; Zhang, Xiao-Xia; He, Ji-Zheng

    2014-01-01

    Soil pollution caused by polycyclic aromatic hydrocarbons (PAHs) is threatening human health and environmental safety. Investigating the relative prevalence of different PAH-degrading genes in PAH-polluted soils and searching for potential bioindicators reflecting the impact of PAH pollution on microbial communities are useful for microbial monitoring, risk evaluation, and potential bioremediation of soils polluted by PAHs. In this study, three functional genes, pdo1, nah, and C12O, which might be involved in the degradation of PAHs from a coke factory, were investigated by real-time quantitative PCR (qPCR) and clone library approaches. The results showed that the pdo1 and C12O genes were more abundant than the nah gene in the soils. There was a significantly positive relationship between the nah or pdo1 gene abundances and PAH content, while there was no correlation between C12O gene abundance and PAH content. Analyses of clone libraries showed that all the pdo1 sequences were grouped into Mycobacterium, while all the nah sequences were classified into three groups: Pseudomonas, Comamonas, and Polaromonas. These results indicated that the abundances of nah and pdo1 genes were positively influenced by levels of PAHs in soil and could be potential microbial indicators reflecting the impact of soil PAH pollution and that Mycobacteria were one of the most prevalent PAHs degraders in these PAH-polluted soils. Principal component analysis (PCA) and correlation analyses between microbial parameters and environmental factors revealed that total carbon (TC), total nitrogen (TN), and dissolved organic carbon (DOC) had positive effects on the abundances of all PAH-degrading genes. It suggests that increasing TC, TN, and DOC inputs could be a useful way to remediate PAH-polluted soils.

  8. A North American Hydroclimate Synthesis (NAHS) of the Common Era

    NASA Astrophysics Data System (ADS)

    Rodysill, Jessica R.; Anderson, Lesleigh; Cronin, Thomas M.; Jones, Miriam C.; Thompson, Robert S.; Wahl, David B.; Willard, Debra A.; Addison, Jason A.; Alder, Jay R.; Anderson, Katherine H.; Anderson, Lysanna; Barron, John A.; Bernhardt, Christopher E.; Hostetler, Steven W.; Kehrwald, Natalie M.; Khan, Nicole S.; Richey, Julie N.; Starratt, Scott W.; Strickland, Laura E.; Toomey, Michael R.; Treat, Claire C.; Wingard, G. Lynn

    2018-03-01

    This study presents a synthesis of century-scale hydroclimate variations in North America for the Common Era (last 2000 years) using new age models of previously published multiple proxy-based paleoclimate data. This North American Hydroclimate Synthesis (NAHS) examines regional hydroclimate patterns and related environmental indicators, including vegetation, lake water elevation, stream flow and runoff, cave drip rates, biological productivity, assemblages of living organisms, and salinity. Centennial-scale hydroclimate anomalies are obtained by iteratively sampling the proxy data on each of thousands of age model realizations and determining the fractions of possible time series indicating that the century-smoothed data was anomalously wet or dry relative to the 100 BCE to 1900 CE mean. Results suggest regionally asynchronous wet and dry periods over multidecadal to centennial timescales and frequent periods of extended regional drought. Most sites indicate drying during previously documented multicentennial periods of warmer Northern Hemisphere temperatures, particularly in the western U.S., central U.S., and Canada. Two widespread droughts were documented by the NAHS: from 50 BCE to 450 CE and from 800 to 1100 CE. Major hydroclimate reorganizations occurred out of sync with Northern Hemisphere temperature variations and widespread wet and dry anomalies occurred during both warm and cool periods. We present a broad assessment of paleoclimate relationships that highlights the potential influences of internal variability and external forcing and supports a prominent role for Pacific and Atlantic Ocean dynamics on century-scale continental hydroclimate.

  9. High sodium intake increases HCO3− absorption in medullary thick ascending limb through adaptations in basolateral and apical Na+/H+ exchangers

    PubMed Central

    George, Thampi; Watts, Bruns A.

    2011-01-01

    A high sodium intake increases the capacity of the medullary thick ascending limb (MTAL) to absorb HCO3−. Here, we examined the role of the apical NHE3 and basolateral NHE1 Na+/H+ exchangers in this adaptation. MTALs from rats drinking H2O or 0.28 M NaCl for 5–7 days were perfused in vitro. High sodium intake increased HCO3− absorption rate by 60%. The increased HCO3− absorptive capacity was mediated by an increase in apical NHE3 activity. Inhibiting basolateral NHE1 with bath amiloride eliminated 60% of the adaptive increase in HCO3− absorption. Thus the majority of the increase in NHE3 activity was dependent on NHE1. A high sodium intake increased basolateral Na+/H+ exchange activity by 89% in association with an increase in NHE1 expression. High sodium intake increased apical Na+/H+ exchange activity by 30% under conditions in which basolateral Na+/H+ exchange was inhibited but did not change NHE3 abundance. These results suggest that high sodium intake increases HCO3− absorptive capacity in the MTAL through 1) an adaptive increase in basolateral NHE1 activity that results secondarily in an increase in apical NHE3 activity; and 2) an adaptive increase in NHE3 activity, independent of NHE1 activity. These studies support a role for NHE1 in the long-term regulation of renal tubule function and suggest that the regulatory interaction whereby NHE1 enhances the activity of NHE3 in the MTAL plays a role in the chronic regulation of HCO3− absorption. The adaptive increases in Na+/H+ exchange activity and HCO3− absorption in the MTAL may play a role in enabling the kidneys to regulate acid-base balance during changes in sodium and volume balance. PMID:21613418

  10. Lysine 300 is essential for stability but not for electrogenic transport of the Escherichia coli NhaA Na+/H+ antiporter

    PubMed Central

    Călinescu, Octavian; Dwivedi, Manish; Patiño-Ruiz, Miyer; Padan, Etana; Fendler, Klaus

    2017-01-01

    Na+/H+ antiporters are located in the cytoplasmic and intracellular membranes and play crucial roles in regulating intracellular pH, Na+, and volume. The NhaA antiporter of Escherichia coli is the best studied member of the Na+/H+ exchanger family and a model system for all related Na+/H+ exchangers, including eukaryotic representatives. Several amino acid residues are important for the transport activity of NhaA, including Lys-300, a residue that has recently been proposed to carry one of the two H+ ions that NhaA exchanges for one Na+ ion during one transport cycle. Here, we sought to characterize the effects of mutating Lys-300 of NhaA to amino acid residues containing side chains of different polarity and length (i.e. Ala, Arg, Cys, His, Glu, and Leu) on transporter stability and function. Salt resistance assays, acridine-orange fluorescence dequenching, solid supported membrane-based electrophysiology, and differential scanning fluorometry were used to characterize Na+ and H+ transport, charge translocation, and thermal stability of the different variants. These studies revealed that NhaA could still perform electrogenic Na+/H+ exchange even in the absence of a protonatable residue at the Lys-300 position. However, all mutants displayed lower thermal stability and reduced ion transport activity compared with the wild-type enzyme, indicating the critical importance of Lys-300 for optimal NhaA structural stability and function. On the basis of these experimental data, we propose a tentative mechanism integrating the functional and structural role of Lys-300. PMID:28330875

  11. Molecular characterization and expression analysis of the Na+/H+ exchanger gene family in Medicago truncatula

    USDA-ARS?s Scientific Manuscript database

    One important mechanism plants use to cope with salinity is keeping the cytosolic Na+ concentration low by sequestering Na+ in vacuoles, a process facilitated by Na+/H+ exchangers (NHX). There are eight NHX genes (NHX1 through NHX8) identified and characterized in Arabidopsis. Bioinformatic analysis...

  12. Solving the Mechanism of Na+/H+ Antiporters Using Molecular Dynamics Simulations

    NASA Astrophysics Data System (ADS)

    Dotson, David L.

    Na+/H+ antiporters are vital membrane proteins for cell homeostasis, transporting Na+ ions in exchange for H+ across the lipid bilayer. In humans, dysfunction of these transporters are implicated in hypertension, heart failure, epilepsy, and autism, making them well-established drug targets. Although experimental structures for bacterial homologs of the human Na+/H+ have been obtained, the detailed mechanism for ion transport is still not well-understood. The most well-studied of these transporters, Escherichia coli NhaA, known to transport 2 H+ for every Na+ extruded, was recently shown to bind H+ and Na+ at the same binding site, for which the two ion species compete. Using molecular dynamics simulations, the work presented in this dissertation shows that Na+ binding disrupts a previously-unidentified salt bridge between two conserved residues, suggesting that one of these residues, Lys300, may participate directly in transport of H+. This work also demonstrates that the conformational change required for ion translocation in a homolog of NhaA, Thermus thermophilus NapA, thought by some to involve only small helical movements at the ion binding site, is a large-scale, rigid-body movement of the core domain relative to the dimerization domain. This elevator-like transport mechanism translates a bound Na+ up to 10 A across the membrane. These findings constitute a major shift in the prevailing thought on the mechanism of these transporters, and serve as an exciting launchpad for new developments toward understanding that mechanism in detail.

  13. A role for Na+/H+ exchange in contraction of guinea pig airways by endothelin-1 in vitro.

    PubMed

    Battistini, B; Filep, J G; Cragoe, E J; Fournier, A; Sirois, P

    1991-03-15

    Endothelin-1-induced contractions of guinea pig tracheal and bronchial strips were dose-dependently attenuated by the amiloride analogues 5-(N-ethyl-N-isopropyl)amiloride (EIPA, 1-10 microM) and 5-(N,N-hexamethylene)amiloride (HMA, 1-10 microM). The calculated Ki values for EIPA and HMA were 0.11 +/- 0.02 microM and 0.06 +/- 0.02 microM in the trachea, and 0.28 +/- 0.11 microM and 0.70 +/- 0.25 microM in the bronchus, respectively. These values are in the same order of magnitude as those reported for inhibition of the Na+/H+ exchange in cells. Amiloride (1-10 microM) was ineffective. These data suggest that activation of the Na+/H+ exchange by ET-1 may be involved in mediating its myotropic action in guinea pig airway smooth muscle.

  14. Integrating mass spectrometry with MD simulations reveals the role of lipids in Na+/H+ antiporters

    NASA Astrophysics Data System (ADS)

    Landreh, Michael; Marklund, Erik G.; Uzdavinys, Povilas; Degiacomi, Matteo T.; Coincon, Mathieu; Gault, Joseph; Gupta, Kallol; Liko, Idlir; Benesch, Justin L. P.; Drew, David; Robinson, Carol V.

    2017-01-01

    Na+/H+ antiporters are found in all kingdoms of life and exhibit catalysis rates that are among the fastest of all known secondary-active transporters. Here we combine ion mobility mass spectrometry and molecular dynamics simulations to study the conformational stability and lipid-binding properties of the Na+/H+ exchanger NapA from Thermus thermophilus and compare this to the prototypical antiporter NhaA from Escherichia coli and the human homologue NHA2. We find that NapA and NHA2, but not NhaA, form stable dimers and do not selectively retain membrane lipids. By comparing wild-type NapA with engineered variants, we show that the unfolding of the protein in the gas phase involves the disruption of inter-domain contacts. Lipids around the domain interface protect the native fold in the gas phase by mediating contacts between the mobile protein segments. We speculate that elevator-type antiporters such as NapA, and likely NHA2, use a subset of annular lipids as structural support to facilitate large-scale conformational changes within the membrane.

  15. Lifetimes and energetics of the first electronically excited states of NaH2O from time-resolved photoelectron imaging

    NASA Astrophysics Data System (ADS)

    Gartmann, Thomas E.; Yoder, Bruce L.; Chasovskikh, Egor; Signorell, Ruth

    2017-09-01

    The energetics and lifetimes of the first electronically excited states (;3p-states;) of NaH2O and NaD2O have been measured by pump-probe (740/780 and 400 nm) photoelectron imaging. The photoelectron spectra of NaH2O show two bands at an electron kinetic energy of 0.14 and 0.38 eV, respectively. We assign the former to excitation via the two energetically close lying ;pπ-states; with flat potential curves in the intermolecular degrees of freedom, and the latter to the excitation via the ;pσ-state; characterized by significantly steeper potential curves. The relaxation of all ;p-states; follows a double exponential decay with a lifetime around 110 ps for the dominant fast component.

  16. Photolabeling of tonoplast from sugar beet cell suspensions by [h]5-(N-methyl-N-isobutyl)-amiloride, an inhibitor of the vacuolar na/h antiport.

    PubMed

    Barkla, B J; Charuk, J H; Cragoe, E J; Blumwald, E

    1990-07-01

    The effects of 5-(N-methyl-N-isobutyl)-amiloride (MIA), an amiloride analog, was tested on the Na(+)/H(+) antiport activity of intact vacuoles and tonoplast vesicles isolated from sugar beet (Beta vulgaris L.) cell suspension cultures. MIA inhibited Na(+)/H(+) exchange in a competitive manner with a K(i) of 2.5 and 5.9 micromolar for DeltapH-dependent (22)Na(+) influx in tonoplast vesicles and Na(+)-dependent H(+) efflux in intact vacuoles, respectively. Scatchard analysis of the binding of [(3)H]MIA to tonoplast membranes revealed a high affinity binding component with a K(d) of 1.3 micromolar. The close relationship between the dissociation constant value obtained and the constants of inhibition for MIA obtained by fluorescence quenching and isotope exchange suggests that the high affinity component represents a class of sites associated with the tonoplast Na(+)/H(+) antiport. Photolabeling of the tonoplast with [(3)H]MIA revealed two sets of polypeptides with a different affinity to amiloride and its analog.

  17. Reduced Epithelial Na+/H+ Exchange Drives Gut Microbial Dysbiosis and Promotes Inflammatory Response in T Cell-Mediated Murine Colitis

    PubMed Central

    Midura-Kiela, Monica T.; Ramalingam, Rajalakshmy; Larmonier, Claire B.; Chase, John H.; Caporaso, J. Gregory; Besselsen, David G.; Ghishan, Fayez K.; Kiela, Pawel R.

    2016-01-01

    Inflammatory bowel diseases (IBD) are associated with functional inhibition of epithelial Na+/H+ exchange. In mice, a selective disruption of NHE3 (Slc9a3), a major apical Na+/H+ exchanger, also promotes IBD-like symptoms and gut microbial dysbiosis. We hypothesized that disruption of Na+/H+ exchange is necessary for the development of dysbiosis, which promotes an exacerbated mucosal inflammatory response. Therefore, we performed a temporal analysis of gut microbiota composition, and mucosal immune response to adoptive T cell transfer was evaluated in Rag2-/- and NHE3-/-/Rag2-/- (DKO) mice with and without broad-spectrum antibiotics. Microbiome (16S profiling), colonic histology, T cell and neutrophil infiltration, mucosal inflammatory tone, and epithelial permeability were analyzed. In adoptive T cell transfer colitis model, Slc9a3 status was the most significant determinant of gut microbial community. In DKO mice, NHE3-deficiency and dysbiosis were associated with dramatically accelerated and exacerbated disease, with rapid body weight loss, increased mucosal T cell and neutrophil influx, increased mucosal cytokine expression, increased permeability, and expansion of CD25-FoxP3+ Tregs; this enhanced susceptibility was alleviated by oral broad-spectrum antibiotics. Based on these results and our previous work, we postulate that epithelial electrolyte homeostasis is an important modulator in the progression of colitis, acting through remodeling of the gut microbial community. PMID:27050757

  18. Nearfield acoustic holography. I - Theory of generalized holography and the development of NAH

    NASA Technical Reports Server (NTRS)

    Maynard, J. D.; Williams, E. G.; Lee, Y.

    1985-01-01

    Because its underlying principles are so fundamental, holography has been studied and applied in many areas of science. Recently, a technique has been developed which takes the maximum advantage of the fundamental principles and extracts much more information from a hologram than is customarily associated with such a measurement. In this paper the fundamental principles of holography are reviewed, and a sound radiation measurement system, called nearfield acoustic holography (NAH), which fully exploits the fundamental principles, is described.

  19. Molecular analysis of the Na+/H+ exchanger gene family and its role in salt stress in Medicago truncatula

    USDA-ARS?s Scientific Manuscript database

    High salinity in irrigation water is detrimental to plant growth and productivity. Plants develop various mechanisms and strategies to cope with salinity. One important mechanism is keeping the cytosolic Na+ concentration low by sequestering Na+ in vacuoles, a process facilitated by Na+/H+ exchanger...

  20. Risk assessment of virus infections in the Oder estuary (southern Baltic) on the basis of spatial transport and virus decay simulations.

    PubMed

    Schernewski, G; Jülich, W D

    2001-05-01

    The large Oder (Szczecin) Lagoon (687 km2) at the German-Polish border, close to the Baltic Sea, suffers from severe eutrophication and water quality problems due to high discharge of water, nutrients and pollutants by the river Oder. Sewage treatment around the lagoon has been very much improved during the last years, but large amounts of sewage still enter the Oder river. Human pathogenic viruses generally can be expected in all surface waters that are affected by municipal sewage. There is an increasing awareness that predisposed persons can be infected by a few infective units or even a single active virus. Another new aspect is, that at least polioviruses attached to suspended particles can be infective for weeks and therefore be transported over long distances. Therefore, the highest risk of virus inputs arise from the large amounts of untreated sewage of the city of Szczecin (Poland), which are released into the river Oder and transported to the lagoon and the Baltic Sea. Summer tourism is the most important economical factor in this coastal region and further growth is expected. Human pathogenic viruses might be a serious problem for bathing water quality and sustainable summer tourism. The potential hazard of virus infections along beaches and shores of the Oder lagoon and adjacent parts of the Baltic Sea is evaluated on the basis of model simulations and laboratory results. We used two scenarios for the Older Lagoon considering free viruses and viruses attached to suspended particle matter. The spatial impact of the average virus release in the city of Szczecin during summer (bathing period) was simulated with a hydrodynamic and particle tracking model. Simulations suggest that due to fast inactivation, free viruses in the water represent a risk only in the river and near the river mouth. On the other hand, viruses attached to suspended matter can affect large areas of the eastern, Polish part of the lagoon (Grosses Haff). At the same time the

  1. Na+/H+ and Na+/NH4+ exchange activities of zebrafish NHE3b expressed in Xenopus oocytes

    PubMed Central

    Ito, Yusuke; Kato, Akira; Hirata, Taku; Hirose, Shigehisa

    2014-01-01

    Zebrafish Na+/H+ exchanger 3b (zNHE3b) is highly expressed in the apical membrane of ionocytes where Na+ is absorbed from ion-poor fresh water against a concentration gradient. Much in vivo data indicated that zNHE3b is involved in Na+ absorption but not leakage. However, zNHE3b-mediated Na+ absorption has not been thermodynamically explained, and zNHE3b activity has not been measured. To address this issue, we overexpressed zNHE3b in Xenopus oocytes and characterized its activity by electrophysiology. Exposure of zNHE3b oocytes to Na+-free media resulted in significant decrease in intracellular pH (pHi) and intracellular Na+ activity (aNai). aNai increased significantly when the cytoplasm was acidified by media containing CO2-HCO3− or butyrate. Activity of zNHE3b was inhibited by amiloride or 5-ethylisopropyl amiloride (EIPA). Although the activity was accompanied by a large hyperpolarization of ∼50 mV, voltage-clamp experiments showed that Na+/H+ exchange activity of zNHE3b is electroneutral. Exposure of zNHE3b oocytes to medium containing NH3/NH4+ resulted in significant decreases in pHi and aNai and significant increase in intracellular NH4+ activity, indicating that zNHE3b mediates the Na+/NH4+ exchange. In low-Na+ (0.5 mM) media, zNHE3b oocytes maintained aNai of 1.3 mM, and Na+-influx was observed when pHi was decreased by media containing CO2-HCO3− or butyrate. These results provide thermodynamic evidence that zNHE3b mediates Na+ absorption from ion-poor fresh water by its Na+/H+ and Na+/NH4+ exchange activities. PMID:24401990

  2. Gene amplification at a locus encoding a putative Na+/H+ antiporter confers sodium and lithium tolerance in fission yeast.

    PubMed Central

    Jia, Z P; McCullough, N; Martel, R; Hemmingsen, S; Young, P G

    1992-01-01

    We have identified a new locus, sodium 2 (sod2) based on selection for increased LiCl tolerance in fission yeast, Schizosaccharomyces pombe. Tolerant strains have enhanced pH-dependent Na+ export capacity and sodium transport experiments suggest that the gene encodes an Na+/H+ antiport. The predicted sod2 gene product can be placed in the broad class of transporters which possess 12 hydrophobic transmembrane domains. The protein shows some sequence similarity to the human and bacterial Na+/H+ antiporters. Overexpression of sod2 increased Na+ export capacity and conferred sodium tolerance. Osmotolerance was not affected and sod2 cells were unaffected for growth in K+. In a sod2 disruption strain cells were incapable of exporting sodium. They were hypersensitive to Na+ or Li+ and could not grow under conditions that approximate pH7. The sod2 gene amplification could be selected stepwise and the degree of such amplification correlated with the level of Na+ or Li+ tolerance. Images PMID:1314171

  3. Photolabeling of Tonoplast from Sugar Beet Cell Suspensions by [3H]5-(N-Methyl-N-Isobutyl)-Amiloride, an Inhibitor of the Vacuolar Na+/H+ Antiport 1

    PubMed Central

    Barkla, Bronwyn J.; Charuk, Jeffrey H. M.; Cragoe, Edward J.; Blumwald, Eduardo

    1990-01-01

    The effects of 5-(N-methyl-N-isobutyl)-amiloride (MIA), an amiloride analog, was tested on the Na+/H+ antiport activity of intact vacuoles and tonoplast vesicles isolated from sugar beet (Beta vulgaris L.) cell suspension cultures. MIA inhibited Na+/H+ exchange in a competitive manner with a Ki of 2.5 and 5.9 micromolar for ΔpH-dependent 22Na+ influx in tonoplast vesicles and Na+-dependent H+ efflux in intact vacuoles, respectively. Scatchard analysis of the binding of [3H]MIA to tonoplast membranes revealed a high affinity binding component with a Kd of 1.3 micromolar. The close relationship between the dissociation constant value obtained and the constants of inhibition for MIA obtained by fluorescence quenching and isotope exchange suggests that the high affinity component represents a class of sites associated with the tonoplast Na+/H+ antiport. Photolabeling of the tonoplast with [3H]MIA revealed two sets of polypeptides with a different affinity to amiloride and its analog. Images Figure 7 PMID:16667602

  4. NaHS restores mitochondrial function and inhibits autophagy by activating the PI3K/Akt/mTOR signalling pathway to improve functional recovery after traumatic brain injury.

    PubMed

    Xu, Kebin; Wu, Fangfang; Xu, Ke; Li, Zhengmao; Wei, Xiaojie; Lu, Qi; Jiang, Ting; Wu, Fenzan; Xu, Xinlong; Xiao, Jian; Chen, Daqing; Zhang, Hongyu

    2018-04-25

    Traumatic brain injury (TBI) is one of the most serious public health problems in the world. TBI causes neurological deficits by triggering secondary injuries. Hydrogen sulfide (H 2 S), a gaseous mediator, has been reported to exert neuroprotective effects in central nervous system diseases, such as TBI. However, the molecular mechanisms involved in this effect are still unclear. The present study was designed to explore the ability of NaHS, a H 2 S donor, to provide neuroprotection in a mouse model of TBI and to discover the associated molecular mechanisms of these protective effects. Here, we found that administration of NaHS not only maintained the integrity of the blood brain barrier (BBB), protected neurons from apoptosis, and promoted remyelination and axonal reparation but also protected mitochondrial function. In addition, we found that autophagy was inhibited after treatment with NaHS following TBI, an effect that was induced by activation of the PI3K/AKT/mTOR signalling pathway. Our study indicated that H 2 S treatment is beneficial for TBI, pointing to H 2 S as a potential therapeutic target for treating TBI. Copyright © 2018. Published by Elsevier B.V.

  5. Salicylic acid deficiency in NahG transgenic lines and sid2 mutants increases seed yield in the annual plant Arabidopsis thaliana

    PubMed Central

    Abreu, Maria Elizabeth; Munné-Bosch, Sergi

    2009-01-01

    Salicylic acid-deficient NahG transgenic lines and sid2 mutants were used to evaluate the role of this compound in the development of the short-lived, annual plant Arabidopsis thaliana, with a particular focus on the interplay between salicylic acid and other phytohormones. Low salicylic acid levels led to increased growth, as well as to smaller abscisic acid levels and reduced damage to PSII (as indicated by Fv/Fm ratios) during the reproductive stages in rosette leaves of NahG transgenic lines and sid2 mutants, compared with wild-type plants. Furthermore, salicylic acid deficiency highly influenced seed yield and composition. Seed production increased by 4.4-fold and 3.5-fold in NahG transgenic lines and sid2 mutants, respectively, compared to the wild type. Salicylic acid deficiency also improved seed composition in terms of antioxidant vitamin concentrations, seeds of salicylic acid-deficient plants showing higher levels of α- and γ-tocopherol (vitamin E) and β-carotene (pro-vitamin A) than seeds of wild-type plants. Seeds of salicylic acid-deficient plants also showed higher nitrogen concentrations than seeds of wild-type plants. It is concluded that (i) the sid2 gene, which encodes for isochorismate synthase, plays a central role in salicylic acid biosynthesis during plant development in A. thaliana, (ii) salicylic acid plays a role in the regulation of growth, senescence, and seed production, (iii) there is a cross-talk between salicylic acid and other phytohormones during plant development, and (iv) the concentrations of antioxidant vitamins in seeds may be influenced by the endogenous levels of salicylic acid in plants. PMID:19188277

  6. Differential Effects of Mutations on the Transport Properties of the Na+/H+ Antiporter NhaA from Escherichia coli*

    PubMed Central

    Mager, Thomas; Braner, Markus; Kubsch, Bastian; Hatahet, Lina; Alkoby, Dudu; Rimon, Abraham; Padan, Etana; Fendler, Klaus

    2013-01-01

    Na+/H+ antiporters show a marked pH dependence, which is important for their physiological function in eukaryotic and prokaryotic cells. In NhaA, the Escherichia coli Na+/H+ antiporter, specific single site mutations modulating the pH profile of the transporter have been described in the past. To clarify the mechanism by which these mutations influence the pH dependence of NhaA, the substrate dependence of the kinetics of selected NhaA variants was electrophysiologically investigated and analyzed with a kinetic model. It is shown that the mutations affect NhaA activity in quite different ways by changing the properties of the binding site or the dynamics of the transporter. In the first case, pK and/or KDNa are altered, and in the second case, the rate constants of the conformational transition between the inside and the outside open conformation are modified. It is shown that residues as far apart as 15–20 Å from the binding site can have a significant impact on the dynamics of the conformational transitions or on the binding properties of NhaA. The implications of these results for the pH regulation mechanism of NhaA are discussed. PMID:23836890

  7. The Na+/H+ Exchanger NHE6 Modulates Endosomal pH to Control Processing of Amyloid Precursor Protein in a Cell Culture Model of Alzheimer Disease*

    PubMed Central

    Prasad, Hari; Rao, Rajini

    2015-01-01

    Early intervention may be key to safe and effective therapies in patients with Alzheimer disease. Endosomal dysfunction is an early step in neurodegeneration. Endosomes are a major site of production of Aβ peptide from the processing of amyloid precursor protein (APP) by clipping enzymes (β- and γ-secretases). The β-secretase enzyme BACE1 requires acidic lumen pH for optimum function, and acid pH promotes Aβ aggregation. The Na+/H+ exchanger NHE6 provides a leak pathway for protons, limiting luminal acidification by proton pumps. Like APP, NHE6 expression was induced upon differentiation of SH-SY5Y neuroblastoma cells and localized to an endosomal compartment. Therefore, we investigated whether NHE6 expression altered APP localization and processing in a stably transfected cell culture model of human APP expression. We show that co-expression with NHE6 or treatment with the Na+/H+ ionophore monensin shifted APP away from the trans-Golgi network into early and recycling endosomes in HEK293 cells. NHE6 alkalinized the endosomal lumen, similar to monensin, and significantly attenuated APP processing and Aβ secretion. In contrast, Aβ production was elevated upon NHE6 knockdown. We show that NHE6 transcript and protein levels are lowered in Alzheimer brains relative to control. These findings, taken together with emerging genetic evidence linking endosomal Na+/H+ exchangers with Alzheimer disease, suggest that proton leak pathways may regulate Aβ generation and contribute to disease etiology. PMID:25561733

  8. The intracellular Na(+)/H(+) exchanger NHE7 effects a Na(+)-coupled, but not K(+)-coupled proton-loading mechanism in endocytosis.

    PubMed

    Milosavljevic, Nina; Monet, Michaël; Léna, Isabelle; Brau, Frédéric; Lacas-Gervais, Sandra; Feliciangeli, Sylvain; Counillon, Laurent; Poët, Mallorie

    2014-05-08

    Vesicular H(+)-ATPases and ClC-chloride transporters are described to acidify intracellular compartments, which also express the highly conserved Na(+)/H(+) exchangers NHE6, NHE7, and NHE9. Mutations of these exchangers cause autism-spectrum disorders and neurodegeneration. NHE6, NHE7, and NHE9 are hypothesized to exchange cytosolic K(+) for H(+) and alkalinize vesicles, but this notion has remained untested in K(+) because their intracellular localization prevents functional measurements. Using proton-killing techniques, we selected a cell line that expresses wild-type NHE7 at the plasma membrane, enabling measurement of the exchanger's transport parameters. We found that NHE7 transports Li(+) and Na(+), but not K(+), is nonreversible in physiological conditions and is constitutively activated by cytosolic H(+). Therefore, NHE7 acts as a proton-loading transporter rather than a proton leak. NHE7 mediates an acidification of intracellular vesicles that is additive to that of V-ATPases and that accelerates endocytosis. This study reveals an unexpected function for vesicular Na(+)/H(+) exchangers and provides clues for understanding NHE-linked neurological disorders. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  9. The Na+/H+ exchanger NHE6 modulates endosomal pH to control processing of amyloid precursor protein in a cell culture model of Alzheimer disease.

    PubMed

    Prasad, Hari; Rao, Rajini

    2015-02-27

    Early intervention may be key to safe and effective therapies in patients with Alzheimer disease. Endosomal dysfunction is an early step in neurodegeneration. Endosomes are a major site of production of Aβ peptide from the processing of amyloid precursor protein (APP) by clipping enzymes (β- and γ-secretases). The β-secretase enzyme BACE1 requires acidic lumen pH for optimum function, and acid pH promotes Aβ aggregation. The Na(+)/H(+) exchanger NHE6 provides a leak pathway for protons, limiting luminal acidification by proton pumps. Like APP, NHE6 expression was induced upon differentiation of SH-SY5Y neuroblastoma cells and localized to an endosomal compartment. Therefore, we investigated whether NHE6 expression altered APP localization and processing in a stably transfected cell culture model of human APP expression. We show that co-expression with NHE6 or treatment with the Na(+)/H(+) ionophore monensin shifted APP away from the trans-Golgi network into early and recycling endosomes in HEK293 cells. NHE6 alkalinized the endosomal lumen, similar to monensin, and significantly attenuated APP processing and Aβ secretion. In contrast, Aβ production was elevated upon NHE6 knockdown. We show that NHE6 transcript and protein levels are lowered in Alzheimer brains relative to control. These findings, taken together with emerging genetic evidence linking endosomal Na(+)/H(+) exchangers with Alzheimer disease, suggest that proton leak pathways may regulate Aβ generation and contribute to disease etiology. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  10. A hydrophobic filter confers the cation selectivity of Zygosaccharomyces rouxii plasma-membrane Na+/H+ antiporter.

    PubMed

    Kinclova-Zimmermannova, Olga; Falson, Pierre; Cmunt, Denis; Sychrova, Hana

    2015-04-24

    Na(+)/H(+) antiporters may recognize all alkali-metal cations as substrates but may transport them selectively. Plasma-membrane Zygosaccharomyces rouxii Sod2-22 antiporter exports Na(+) and Li(+), but not K(+). The molecular basis of this selectivity is unknown. We combined protein structure modeling, site-directed mutagenesis, phenotype analysis and cation efflux measurements to localize and characterize the cation selectivity region. A three-dimensional model of the ZrSod2-22 transmembrane domain was generated based on the X-ray structure of the Escherichia coli NhaA antiporter and primary sequence alignments with homologous yeast antiporters. The model suggested a close proximity of Thr141, Ala179 and Val375 from transmembrane segments 4, 5 and 11, respectively, forming a hydrophobic hole in the putative cation pathway's core. A series of mutagenesis experiments verified the model and showed that structural modifications of the hole resulted in altered cation selectivity and transport activity. The triple ZrSod2-22 mutant T141S-A179T-V375I gained K(+) transport capacity. The point mutation A179T restricted the antiporter substrate specificity to Li(+) and reduced its transport activity, while serine at this position preserved the native cation selectivity. The negative effect of the A179T mutation can be eliminated by introducing a second mutation, T141S or T141A, in the preceding transmembrane domain. Our experimental results confirm that the three residues found through modeling play a central role in the determination of cation selectivity and transport activity in Z. rouxii Na(+)/H(+) antiporter and that the cation selectivity can be modulated by repositioning a single local methyl group. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. [Old medical dissertations in the field of obstetrics and gynaecology at the University Frankfurt-on-Oder (Viadrina), 1700-1811].

    PubMed

    Rummler, Siegbert

    2008-01-01

    Based on an analysis of the medical dissertations which have survived from the University of Frankfurt-on-Oder (Viadrina), this paper illustrates the importance of old medical dissertations as historical sources. For 389 out of 570 medical students who received their medical doctorate at the Viadrina between the years 1700 and 1811, the topics of their dissertations have been ascertained. 15 dissertations on obstetrical and gynaecological topics are more closely analysed.

  12. Differential Stimulation of the Na+/H+ Exchanger Determines Chloroquine Uptake in Plasmodium falciparum

    PubMed Central

    Wünsch, Stefan; Sanchez, Cecilia P.; Gekle, Michael; Große-Wortmann, Lars; Wiesner, Jochen; Lanzer, Michael

    1998-01-01

    Here we describe the identification and characterization of a physiological marker that is associated with the chloroquine-resistant (CQR) phenotype in the human malarial parasite Plasmodium falciparum. Single cell in vivo pH measurements revealed that CQR parasites consistently have an elevated cytoplasmic pH compared to that of chloroquine-sensitive (CQS) parasites because of a constitutively activated Na+/H+ exchanger (NHE). Together, biochemical and physiological data suggest that chloroquine activates the plasmodial NHE of CQS parasites, resulting in a transitory phase of rapid sodium/hydrogen ion exchange during which chloroquine is taken up by this protein. The constitutively stimulated NHE of CQR parasites are capable of little or no further activation by chloroquine. We propose that the inability of chloroquine to stimulate its own uptake through the constitutively activated NHE of resistant parasites constitutes a minimal and necessary event in the generation of the chloroquine-resistant phenotype. PMID:9442109

  13. Tonoplast Na+/H+ Antiport Activity and Its Energization by the Vacuolar H+-ATPase in the Halophytic Plant Mesembryanthemum crystallinum L.

    PubMed Central

    Barkla, B. J.; Zingarelli, L.; Blumwald, E.; Smith, JAC.

    1995-01-01

    Tonoplast vesicles were isolated from leaf mesophyll tissue of the inducible Crassulacean acid metabolism plant Mesembryanthemum crystallinum to investigate the mechanism of vacuolar Na+ accumulation in this halophilic species. In 8-week-old plants exposed to 200 mM NaCl for 2 weeks, tonoplast H+-ATPase activity was approximately doubled compared with control plants of the same age, as determined by rates of both ATP hydrolysis and ATP-dependent H+ transport. Evidence was also obtained for the presence of an electroneutral Na+/H+ antiporter at the tonoplast that is constitutively expressed, since extravesicular Na+ was able to dissipate a pre-existing transmembrane pH gradient. Initial rates of H+ efflux showed saturation kinetics with respect to extravesicular Na+ concentration and were 2.1-fold higher from vesicles of salt-treated plants compared with the controls. Na+-dependent H+ efflux also showed a high selectivity for Na+ over K+, was insensitive to the transmembrane electrical potential difference, and was more than 50% inhibited by 200 [mu]M N-amidino-3,5-diamino-6-chloropyrazinecarboxamide hydrochloride. The close correlation between increased Na+/H+ antiport and H+-ATPase activities in response to salt treatment suggests that accumulation of the very high concentrations of vacuolar Na+ found in M. crystallinum is energized by the H+ electrochemical gradient across the tonoplast. PMID:12228611

  14. Tonoplast Na+/H+ Antiport Activity and Its Energization by the Vacuolar H+-ATPase in the Halophytic Plant Mesembryanthemum crystallinum L.

    PubMed

    Barkla, B. J.; Zingarelli, L.; Blumwald, E.; Smith, JAC.

    1995-10-01

    Tonoplast vesicles were isolated from leaf mesophyll tissue of the inducible Crassulacean acid metabolism plant Mesembryanthemum crystallinum to investigate the mechanism of vacuolar Na+ accumulation in this halophilic species. In 8-week-old plants exposed to 200 mM NaCl for 2 weeks, tonoplast H+-ATPase activity was approximately doubled compared with control plants of the same age, as determined by rates of both ATP hydrolysis and ATP-dependent H+ transport. Evidence was also obtained for the presence of an electroneutral Na+/H+ antiporter at the tonoplast that is constitutively expressed, since extravesicular Na+ was able to dissipate a pre-existing transmembrane pH gradient. Initial rates of H+ efflux showed saturation kinetics with respect to extravesicular Na+ concentration and were 2.1-fold higher from vesicles of salt-treated plants compared with the controls. Na+-dependent H+ efflux also showed a high selectivity for Na+ over K+, was insensitive to the transmembrane electrical potential difference, and was more than 50% inhibited by 200 [mu]M N-amidino-3,5-diamino-6-chloropyrazinecarboxamide hydrochloride. The close correlation between increased Na+/H+ antiport and H+-ATPase activities in response to salt treatment suggests that accumulation of the very high concentrations of vacuolar Na+ found in M. crystallinum is energized by the H+ electrochemical gradient across the tonoplast.

  15. Na/H and k/h antiport in root membrane vesicles isolated from the halophyte atriplex and the glycophyte cotton.

    PubMed

    Hassidim, M; Braun, Y; Lerner, H R; Reinhold, L

    1990-12-01

    Proton fluxes have been followed into and out of membrane vesicles isolated from the roots of the halophyte Atriplex nummularia and the glycophyte Gossypium hirsutum, with the aid of the DeltapH probe [(14)C]methylamine. Evidence is presented for the operation of Na(+)/H(+) and K(+)/H(+) antiporters in the membranes of both plants. Cation supply after a pH gradient has been set up across the vesicle membrane (either as a result of providing ATP to the H(+)-ATPase or by imposing an artificial pH gradient) brings about dissipation of the DeltapH, but does not depolarize the membrane potential as observed in similar experiments, but in the absence of Cl(-), using the DeltaPsi probe SCN(-). Cation/H(+) exchange is thus indicated. This exchange is not due to nonspecific electric coupling, nor to competition for anionic adsorption sites on the membrane, nor to inhibition of the H(+)-ATPase; coupling of the opposed cation and H(+) fluxes by a membrane component is the most likely explanation. Saturation kinetics have been observed for both Na(+)/H(+) and K(+)/H(+) antiport in Atriplex. Moreover, additive effects are obtained when Na(+) is supplied together with saturating concentrations of K(+), and vice versa, suggesting that separate antiporters for Na(+) and for K(+) may be operating. In the case of both Atriplex and Gossypium evidence was obtained suggesting the presence of antiporters in both plasmalemma and tonoplast.

  16. Na+/H+ and K+/H+ Antiport in Root Membrane Vesicles Isolated from the Halophyte Atriplex and the Glycophyte Cotton 1

    PubMed Central

    Hassidim, Miriam; Braun, Yael; Lerner, Henri R.; Reinhold, Leonora

    1990-01-01

    Proton fluxes have been followed into and out of membrane vesicles isolated from the roots of the halophyte Atriplex nummularia and the glycophyte Gossypium hirsutum, with the aid of the ΔpH probe [14C]methylamine. Evidence is presented for the operation of Na+/H+ and K+/H+ antiporters in the membranes of both plants. Cation supply after a pH gradient has been set up across the vesicle membrane (either as a result of providing ATP to the H+-ATPase or by imposing an artificial pH gradient) brings about dissipation of the ΔpH, but does not depolarize the membrane potential as observed in similar experiments, but in the absence of Cl−, using the ΔΨ probe SCN−. Cation/H+ exchange is thus indicated. This exchange is not due to nonspecific electric coupling, nor to competition for anionic adsorption sites on the membrane, nor to inhibition of the H+-ATPase; coupling of the opposed cation and H+ fluxes by a membrane component is the most likely explanation. Saturation kinetics have been observed for both Na+/H+ and K+/H+ antiport in Atriplex. Moreover, additive effects are obtained when Na+ is supplied together with saturating concentrations of K+, and vice versa, suggesting that separate antiporters for Na+ and for K+ may be operating. In the case of both Atriplex and Gossypium evidence was obtained suggesting the presence of antiporters in both plasmalemma and tonoplast. PMID:16667918

  17. Functional Characterization of Na+/H+ Exchangers of Intracellular Compartments Using Proton-killing Selection to Express Them at the Plasma Membrane

    PubMed Central

    Monet, Michael; Birgy-Barelli, Eléonore; Léna, Isabelle; Counillon, Laurent

    2015-01-01

    Endosomal acidification is critical for a wide range of processes, such as protein recycling and degradation, receptor desensitization, and neurotransmitter loading in synaptic vesicles. This acidification is described to be mediated by proton ATPases, coupled to ClC chloride transporters. Highly-conserved electroneutral protons transporters, the Na+/H+ exchangers (NHE) 6, 7 and 9 are also expressed in these compartments. Mutations in their genes have been linked with human cognitive and neurodegenerative diseases. Paradoxically, their roles remain elusive, as their intracellular localization has prevented detailed functional characterization. This manuscript shows a method to solve this problem. This consists of the selection of mutant cell lines, capable of surviving acute cytosolic acidification by retaining intracellular NHEs at the plasma membrane. It then depicts two complementary protocols to measure the ion selectivity and activity of these exchangers: (i) one based on intracellular pH measurements using fluorescence video microscopy, and (ii) one based on the fast kinetics of lithium uptake. Such protocols can be extrapolated to measure other non-electrogenic transporters. Furthermore, the selection procedure presented here generates cells with an intracellular retention defective phenotype. Therefore these cells will also express other vesicular membrane proteins at the plasma membrane. The experimental strategy depicted here may therefore constitute a potentially powerful tool to study other intracellular proteins that will be then expressed at the plasma membrane together with the vesicular Na+/H+ exchangers used for the selection. PMID:25867523

  18. Functional characterization of Na+/H+ exchangers of intracellular compartments using proton-killing selection to express them at the plasma membrane.

    PubMed

    Milosavljevic, Nina; Poët, Mallorie; Monet, Michael; Birgy-Barelli, Eléonore; Léna, Isabelle; Counillon, Laurent

    2015-03-30

    Endosomal acidification is critical for a wide range of processes, such as protein recycling and degradation, receptor desensitization, and neurotransmitter loading in synaptic vesicles. This acidification is described to be mediated by proton ATPases, coupled to ClC chloride transporters. Highly-conserved electroneutral protons transporters, the Na+/H+ exchangers (NHE) 6, 7 and 9 are also expressed in these compartments. Mutations in their genes have been linked with human cognitive and neurodegenerative diseases. Paradoxically, their roles remain elusive, as their intracellular localization has prevented detailed functional characterization. This manuscript shows a method to solve this problem. This consists of the selection of mutant cell lines, capable of surviving acute cytosolic acidification by retaining intracellular NHEs at the plasma membrane. It then depicts two complementary protocols to measure the ion selectivity and activity of these exchangers: (i) one based on intracellular pH measurements using fluorescence video microscopy, and (ii) one based on the fast kinetics of lithium uptake. Such protocols can be extrapolated to measure other non-electrogenic transporters. Furthermore, the selection procedure presented here generates cells with an intracellular retention defective phenotype. Therefore these cells will also express other vesicular membrane proteins at the plasma membrane. The experimental strategy depicted here may therefore constitute a potentially powerful tool to study other intracellular proteins that will be then expressed at the plasma membrane together with the vesicular Na+/H+ exchangers used for the selection.

  19. Rapamycin Inhibition of mTOR Reduces Levels of the Na+/H+ Exchanger 3 in Intestines of Mice and Humans, Leading to Diarrhea

    PubMed Central

    Yang, Jun; Zhao, Xiaofeng; Patel, Archana; Potru, Rachana; Azizi-Ghannad, Sadra; Dolinger, Michael; Mazurkiewicz, Joseph; Conti, David; Jones, David; Huang, Yunfei; Zhu, Xinjun

    2016-01-01

    Background & Aims The immunosuppressant rapamycin frequently causes non-infectious diarrhea in recipients of organ transplants. We investigated the mechanisms of this process. Methods We performed a retrospective analysis of renal transplant recipients treated with rapamycin from 2003 through 2010 at Albany Medical College, collecting data on serum levels of rapamycin. Levels of the Na+/H+ exchanger 3 (NHE3) were measured in human ileal biopsies from patients who did and did not receive rapamycin (controls), in ileum tissues from rats or mice given rapamycin, and in mice with intestine-specific disruption of Mtor (mTORf/f:Villin-cre mice) or Atg7 (Atg7flox/flox; Villin-Cre). Exchange activity and intestinal water absorption were measured using a pH-sensitive dye and small intestine perfusion, respectively. Results Episodes of non-infectious diarrhea occurred in organ recipients following increases in serum levels of rapamycin. Expression of NHE3 was reduced in the ileal brush border of patients with diarrhea. In rats and mice, continuous administration of low doses of rapamycin reduced levels of NHE3 in intestinal tissues; this effect was not observed in mice with intestinal deletion of ATG7, indicating that autophagy is required for the reduction. Administration of single high doses of rapamycin to mice, to model the spikes in rapamycin levels that occur in patients with severe diarrheal episodes, resulted in reduced phosphorylation of S6 and AKT in ileal tissues, indicating inhibition of the mTOR complex (mTORC1 and mTORC2). Intestines of mice with intestine-specific deletion of mTOR were dilated and contained large amount of liquid stools; they also had reduced levels of total NHE3 and NHERF1, compared with control mice. We observed a significant reduction in Na+/H+ exchange activity in ileum tissues from these mice. Conclusions Rapamycin inhibition of mTOR reduces levels of NHE3 and Na+/H+ exchange activity in intestinal tissues of patients and rodents. This

  20. Rapamycin Inhibition of mTOR Reduces Levels of the Na+/H+ Exchanger 3 in Intestines of Mice and Humans, Leading to Diarrhea.

    PubMed

    Yang, Jun; Zhao, Xiaofeng; Patel, Archana; Potru, Rachana; Azizi-Ghannad, Sadra; Dolinger, Michael; Cao, James; Bartholomew, Catherine; Mazurkiewicz, Joseph; Conti, David; Jones, David; Huang, Yunfei; Zhu, Xinjun Cindy

    2015-07-01

    The immunosuppressant rapamycin frequently causes noninfectious diarrhea in organ transplant recipients. We investigated the mechanisms of this process. We performed a retrospective analysis of renal transplant recipients treated with rapamycin from 2003 through 2010 at Albany Medical College, collecting data on serum levels of rapamycin. Levels of the Na+/H+ exchanger 3 (NHE3) were measured in human ileal biopsy specimens from patients who did and did not receive rapamycin (controls), in ileum tissues from rats or mice given rapamycin, and in mice with intestine-specific disruption of mammalian target of rapamycin (Mtor) (mTOR(f/f):Villin-cre mice) or Atg7 (Atg7(flox/flox); Villin-Cre). Exchange activity and intestinal water absorption were measured using a pH-sensitive dye and small intestine perfusion, respectively. Episodes of noninfectious diarrhea occurred in organ recipients after increases in serum levels of rapamycin. The expression of NHE3 was reduced in the ileal brush border of patients with diarrhea. In rats and mice, continuous administration of low doses of rapamycin reduced levels of NHE3 in intestinal tissues; this effect was not observed in mice with intestinal deletion of ATG7, indicating that autophagy is required for the reduction. Administration of single high doses of rapamycin to mice, to model the spikes in rapamycin levels that occur in patients with severe diarrheal episodes, resulted in reduced phosphorylation of S6 and AKT in ileal tissues, indicating inhibition of the mTOR complex (mTORC1 and mTORC2). The intestines of mice with intestine-specific deletion of mTOR were dilated and contained large amounts of liquid stools; they also had reduced levels of total NHE3 and NHERF1 compared with control mice. We observed a significant reduction in Na(+)/H(+) exchange activity in ileum tissues from these mice. Rapamycin inhibition of mTOR reduces levels of NHE3 and Na(+)/H(+) exchange activity in intestinal tissues of patients and rodents

  1. Hyper-polyhedron model applied to molecular screening of guanidines as Na/H exchange inhibitors.

    PubMed

    Bao, Xin-Hua; Lu, Wen-Cong; Liu, Liang; Chen, Nian-Yi

    2003-05-01

    To investigate structure-activity relationships of N-(3-Oxo-3,4-dihydro-2H-benzo[1,4]oxazine-6-carbonyl) guanidines in Na/H exchange inhibitory activities and probe into a new method of the computer-aided molecular screening. The hyper-polyhedron model (HPM) was proposed in our lab. The samples with probably higher activities could be determined in such a way that their representing points should be in the hyper-polyhedron region where all known samples with high activities were distributed. And the predictive ability of different methods available was tested by the cross-validation experiment. The accurate rate of molecular screening of N-(3-Oxo-3,4-dihydro-2H-benzo[1,4]oxazine-6-carbonyl) guanidines by HPM was much higher than that obtained by PCA (principal component analysis) and Fisher methods for the data set available here. Therefore, HPM could be used as a powerful tool for screening new compounds with probably higher activities.

  2. Analysis of cardiovascular responses to the H2S donors Na2S and NaHS in the rat

    PubMed Central

    Yoo, Daniel; Jupiter, Ryan C.; Pankey, Edward A.; Reddy, Vishwaradh G.; Edward, Justin A.; Swan, Kevin W.; Peak, Taylor C.; Mostany, Ricardo

    2015-01-01

    Hydrogen sulfide (H2S) is an endogenous gaseous molecule formed from L-cysteine in vascular tissue. In the present study, cardiovascular responses to the H2S donors Na2S and NaHS were investigated in the anesthetized rat. The intravenous injections of Na2S and NaHS 0.03–0.5 mg/kg produced dose-related decreases in systemic arterial pressure and heart rate, and at higher doses decreases in cardiac output, pulmonary arterial pressure, and systemic vascular resistance. H2S infusion studies show that decreases in systemic arterial pressure, heart rate, cardiac output, and systemic vascular resistance are well-maintained, and responses to Na2S are reversible. Decreases in heart rate were not blocked by atropine, suggesting that the bradycardia was independent of parasympathetic activation and was mediated by an effect on the sinus node. The decreases in systemic arterial pressure were not attenuated by hexamethonium, glybenclamide, Nw-nitro-l-arginine methyl ester hydrochloride, sodium meclofenamate, ODQ, miconazole, 5-hydroxydecanoate, or tetraethylammonium, suggesting that ATP-sensitive potassium channels, nitric oxide, arachidonic acid metabolites, cyclic GMP, p450 epoxygenase metabolites, or large conductance calcium-activated potassium channels are not involved in mediating hypotensive responses to the H2S donors in the rat and that responses are not centrally mediated. The present data indicate that decreases in systemic arterial pressure in response to the H2S donors can be mediated by decreases in vascular resistance and cardiac output and that the donors have an effect on the sinus node independent of the parasympathetic system. The present data indicate that the mechanism of the peripherally mediated hypotensive response to the H2S donors is uncertain in the intact rat. PMID:26071540

  3. Na+/H+ exchange activity during phagocytosis in human neutrophils: role of Fcgamma receptors and tyrosine kinases

    PubMed Central

    1996-01-01

    In neutrophils, binding and phagocytosis facilitate subsequent intracellular killing of microorganisms. Activity of Na+/H+ exchangers (NHEs) participates in these events, especially in regulation of intracellular pH (pHi) by compensating for the H+ load generated by the respiratory burst. Despite the importance of these functions, comparatively little is known regarding the nature and regulation of NHE(s) in neutrophils. The purpose of this study was to identify which NHE(s) are expressed in neutrophils and to elucidate the mechanisms regulating their activity during phagocytosis. Exposure of cells to the phagocytic stimulus opsonized zymosan (OpZ) induced a transient cytosolic acidification followed by a prolonged alkalinization. The latter was inhibited in Na+-free medium and by amiloride analogues and therefore was due to activation of Na+/H+ exchange. Reverse transcriptase PCR and cDNA sequencing demonstrated that mRNA for the NHE-1 but not for NHE-2, 3, or 4 isoforms of the exchanger was expressed. Immunoblotting of purified plasma membranes with isoform- specific antibodies confirmed the presence of NHE-1 protein in neutrophils. Since phagocytosis involves Fcgamma (FcgammaR) and complement receptors such as CR3 (a beta2 integrin) which are linked to pathways involving alterations in intracellular [Ca2+]i and tyrosine phosphorylation, we studied these pathways in relation to activation of NHE-1. Cross-linking of surface bound antibodies (mAb) directed against FcgammaRs (FcgammaRII > FcgammaRIII) but not beta2 integrins induced an amiloride-sensitive cytosolic alkalinization. However, anti-beta2 integrin mAb diminished OpZ-induced alkalinization suggesting that NHE- 1 activation involved cooperation between integrins and FcgammaRs. The tyrosine kinase inhibitors genistein and herbimycin blocked cytosolic alkalinization after OpZ or FcgammaR cross-linking suggesting that tyrosine phosphorylation was involved in NHE-I activation. An increase in [Ca2+]i was not

  4. Genes encoding the vacuolar Na+/H+ exchanger and flower coloration.

    PubMed

    Yamaguchi, T; Fukada-Tanaka, S; Inagaki, Y; Saito, N; Yonekura-Sakakibara, K; Tanaka, Y; Kusumi, T; Iida, S

    2001-05-01

    Vacuolar pH plays an important role in flower coloration: an increase in the vacuolar pH causes blueing of flower color. In the Japanese morning glory (Ipomoea nil or Pharbitis nil), a shift from reddish-purple buds to blue open flowers correlates with an increase in the vacuolar pH. We describe details of the characterization of a mutant that carries a recessive mutation in the Purple (Pr) gene encoding a vacuolar Na+/H+ exchanger termed InNHX1. The genome of I. nil carries one copy of the Pr (or InNHX1) gene and its pseudogene, and it showed functional complementation to the yeast nhx1 mutation. The mutant of I. nil, called purple (pr), showed a partial increase in the vacuolar pH during flower-opening and its reddish-purple buds change into purple open flowers. The vacuolar pH in the purple open flowers of the mutant was significantly lower than that in the blue open flowers. The InNHX1 gene is most abundantly expressed in the petals at around 12 h before flower-opening, accompanying the increase in the vacuolar pH for the blue flower coloration. No such massive expression was observed in the petunia flowers. Since the NHX1 genes that promote the transport of Na+ into the vacuoles have been regarded to be involved in salt tolerance by accumulating Na+ in the vacuoles, we can add a new biological role for blue flower coloration in the Japanese morning glory by the vacuolar alkalization.

  5. High Capacity Na+/H+ Exchange Activity in Mineralizing Osteoblasts

    PubMed Central

    Liu, Li; Schlesinger, Paul H.; Slack, Nicole M.; Friedman, Peter A.; Blair, Harry C.

    2015-01-01

    Osteoblasts synthesize bone in polarized groups of cells sealed by tight junctions. Large amounts of acid are produced as bone mineral is precipitated. We addressed the mechanism by which cells manage this acid load by measuring intracellular pH (pHi) in non-transformed osteoblasts in response to weak acid or bicarbonate loading. Basal pHi in mineralizing osteoblasts was ∼7.3 and decreased by ∼ 1.4 units upon replacing extracellular Na+ with N-methyl-d-glucamine. Loading with 40 mM acetic or propionic acids, in normal extracellular Na+, caused only mild cytosolic acidification. In contrast, in Na+-free solutions, weak acids reduced pHi dramatically. After Na+ reintroduction, pHi recovered rapidly, in keeping with Na+/H+exchanger (NHE) activity. Sodium-dependent pHi recovery from weak acid loading was inhibited by amiloride with the Ki consistent with NHEs. NHE1 and NHE6 were expressed strongly, and expression was upregulated highly, by mineralization, in human osteoblasts. Antibody labeling of mouse bone showed NHE1 on basolateral surfaces of all osteoblasts. NHE6 occurred on basolateral surfaces of osteoblasts mainly in areas of mineralization. Conversely, elevated HCO3- alkalinized osteoblasts, and pH recovered in medium containing CI-, with or without Na+, in keeping with Na+-independent CI-/HCO3- exchange. The exchanger AE2 also occurred on the basolateral surface of osteoblasts, consistent with CI-/HCO3- exchange for elimination of metabolic carbonate. Overexpression of NHE6 or knockdown of NHE1 in MG63 human osteosarcoma cells confirmed roles of NHE1 and NHE6 in maintaining pHi. We conclude that in mineralizing osteoblasts, slightly basic basal pHi is maintained, and external acid load is dissipated, by high-capacity Na+/H+ exchange via NHE1 and NHE6. PMID:21413028

  6. Revealing isomerism in sodium-water clusters: Photoionization spectra of Na(H2O)n (n = 2-90)

    NASA Astrophysics Data System (ADS)

    Dierking, Christoph W.; Zurheide, Florian; Zeuch, Thomas; Med, Jakub; Parez, Stanislav; Slavíček, Petr

    2017-06-01

    Soft ionization of sodium tagged polar clusters is increasingly used as a powerful technique for sizing and characterization of small aerosols with possible application, e.g., in atmospheric chemistry or combustion science. Understanding the structure and photoionization of the sodium doped clusters is critical for such applications. In this work, we report on measurements of photoionization spectra for sodium doped water clusters containing 2-90 water molecules. While most of the previous studies focused on the ionization threshold of the Na(H2O)n clusters, we provide for the first time full photoionization spectra, including the high-energy region, which are used as reference for a comparison with theory. As reported in previous work, we have seen an initial drop of the appearance ionization energy with cluster size to values of about 3.2 eV for n <5 . In the size range from n = 5 to n = 15, broad ion yield curves emerge; for larger clusters, a constant range between signal appearance (˜2.8 eV) and signal saturation (˜4.1 eV) has been observed. The measurements are interpreted with ab initio calculations and ab initio molecular dynamics simulations for selected cluster sizes (n ≤ 15). The simulations revealed theory shortfalls when aiming at quantitative agreement but allowed us identifying structural motifs consistent with the observed ionization energy distributions. We found a decrease in the ionization energy with increasing coordination of the Na atom and increasing delocalization of the Na 3s electron cloud. The appearance ionization energy is determined by isomers with fully solvated sodium and a highly delocalized electron cloud, while both fully and incompletely solvated isomers with localized electron clouds can contribute to the high energy part of the photoionization spectrum. Simulations at elevated temperatures show an increased abundance of isomers with low ionization energies, an entropic effect enabling size selective infrared action

  7. Revealing isomerism in sodium-water clusters: Photoionization spectra of Na(H2O)n (n = 2-90).

    PubMed

    Dierking, Christoph W; Zurheide, Florian; Zeuch, Thomas; Med, Jakub; Parez, Stanislav; Slavíček, Petr

    2017-06-28

    Soft ionization of sodium tagged polar clusters is increasingly used as a powerful technique for sizing and characterization of small aerosols with possible application, e.g., in atmospheric chemistry or combustion science. Understanding the structure and photoionization of the sodium doped clusters is critical for such applications. In this work, we report on measurements of photoionization spectra for sodium doped water clusters containing 2-90 water molecules. While most of the previous studies focused on the ionization threshold of the Na(H 2 O) n clusters, we provide for the first time full photoionization spectra, including the high-energy region, which are used as reference for a comparison with theory. As reported in previous work, we have seen an initial drop of the appearance ionization energy with cluster size to values of about 3.2 eV for n<5. In the size range from n = 5 to n = 15, broad ion yield curves emerge; for larger clusters, a constant range between signal appearance (∼2.8 eV) and signal saturation (∼4.1 eV) has been observed. The measurements are interpreted with ab initio calculations and ab initio molecular dynamics simulations for selected cluster sizes (n≤ 15). The simulations revealed theory shortfalls when aiming at quantitative agreement but allowed us identifying structural motifs consistent with the observed ionization energy distributions. We found a decrease in the ionization energy with increasing coordination of the Na atom and increasing delocalization of the Na 3s electron cloud. The appearance ionization energy is determined by isomers with fully solvated sodium and a highly delocalized electron cloud, while both fully and incompletely solvated isomers with localized electron clouds can contribute to the high energy part of the photoionization spectrum. Simulations at elevated temperatures show an increased abundance of isomers with low ionization energies, an entropic effect enabling size selective infrared action

  8. Purification and Functional Reconstitution of a Seven-Subunit Mrp-Type Na+/H+ Antiporter

    PubMed Central

    Morino, Masato; Suzuki, Toshiharu; Ito, Masahiro

    2014-01-01

    Mrp antiporters and their homologues in the cation/proton antiporter 3 family of the Membrane Transporter Database are widely distributed in bacteria. They have major roles in supporting cation and cytoplasmic pH homeostasis in many environmental, extremophilic, and pathogenic bacteria. These antiporters require six or seven hydrophobic proteins that form hetero-oligomeric complexes, while most other cation/proton antiporters require only one membrane protein for their activity. The resemblance of three Mrp subunits to membrane-embedded subunits of the NADH:quinone oxidoreductase of respiratory chains and to subunits of several hydrogenases has raised interest in the evolutionary path and commonalities of their proton-translocating domains. In order to move toward a greater mechanistic understanding of these unusual antiporters and to rigorously demonstrate that they function as secondary antiporters, powered by an imposed proton motive force, we established a method for purification and functional reconstitution of the seven-subunit Mrp antiporter from alkaliphilic Bacillus pseudofirmus OF4. Na+/H+ antiporter activity was demonstrated by a fluorescence-based assay with proteoliposomes in which the Mrp complex was coreconstituted with a bacterial FoF1-ATPase. Proton pumping by the ATPase upon addition of ATP generated a proton motive force across the membranes that powered antiporter activity upon subsequent addition of Na+. PMID:24142251

  9. Purification and functional reconstitution of a seven-subunit mrp-type na+/h+ antiporter.

    PubMed

    Morino, Masato; Suzuki, Toshiharu; Ito, Masahiro; Krulwich, Terry Ann

    2014-01-01

    Mrp antiporters and their homologues in the cation/proton antiporter 3 family of the Membrane Transporter Database are widely distributed in bacteria. They have major roles in supporting cation and cytoplasmic pH homeostasis in many environmental, extremophilic, and pathogenic bacteria. These antiporters require six or seven hydrophobic proteins that form hetero-oligomeric complexes, while most other cation/proton antiporters require only one membrane protein for their activity. The resemblance of three Mrp subunits to membrane-embedded subunits of the NADH:quinone oxidoreductase of respiratory chains and to subunits of several hydrogenases has raised interest in the evolutionary path and commonalities of their proton-translocating domains. In order to move toward a greater mechanistic understanding of these unusual antiporters and to rigorously demonstrate that they function as secondary antiporters, powered by an imposed proton motive force, we established a method for purification and functional reconstitution of the seven-subunit Mrp antiporter from alkaliphilic Bacillus pseudofirmus OF4. Na(+)/H(+) antiporter activity was demonstrated by a fluorescence-based assay with proteoliposomes in which the Mrp complex was coreconstituted with a bacterial FoF1-ATPase. Proton pumping by the ATPase upon addition of ATP generated a proton motive force across the membranes that powered antiporter activity upon subsequent addition of Na(+).

  10. A mechanism for the activation of the Na/H exchanger NHE-1 by cytoplasmic acidification and mitogens

    PubMed Central

    Lacroix, Jérôme; Poët, Mallorie; Maehrel, Céline; Counillon, Laurent

    2004-01-01

    Eukaryotic cells constantly have to fight against internal acidification. In mammals, this task is mainly performed by the ubiquitously expressed electroneutral Na+/H+ exchanger NHE-1, which activates in a cooperative manner when cells become acidic. Despite its biological importance, the mechanism of this activation is still poorly understood, the most commonly accepted hypothesis being the existence of a proton-sensor site on the internal face of the transporter. This work uncovers mutations that lead to a nonallosteric form of the exchanger and demonstrates that NHE-1 activation is best described by a Monod–Wyman–Changeux concerted mechanism for a dimeric transporter. During intracellular acidification, a low-affinity form of NHE-1 is converted into a form possessing a higher affinity for intracellular protons, with no requirement for an additional proton-sensor site on the protein. This new mechanism also explains the activation of the exchanger by growth signals, which shift the equilibrium towards the high-affinity form. PMID:14710192

  11. Cevimeline-induced monophasic salivation from the mouse submandibular gland: decreased Na+ content in saliva results from specific and early activation of Na+/H+ exchange.

    PubMed

    Kondo, Yusuke; Nakamoto, Tetsuji; Mukaibo, Taro; Kidokoro, Manami; Masaki, Chihiro; Hosokawa, Ryuji

    2011-04-01

    Cevimeline and pilocarpine are muscarinic agonists used clinically to treat dry mouth. In this study, we explored fluid secretion from mouse submandibular glands to determine the mechanism of cevimeline, pilocarpine, and an experimentally used agent carbachol. Cevimeline evoked almost the same amount of secretion at concentrations from 30 μM to 1 mM. Pilocarpine also induced secretion at a concentration as low as 1 μM and was the most powerful secretagogue at 10 μM. Secretion was induced by carbachol at 0.1 μM, with maximum secretion at 1.0 μM. Cevimeline induced monophasic secretion at all concentrations tested, whereas higher concentrations of pilocarpine and carbachol induced secretion with variable kinetics, i.e., an initial transient high flow rate, followed by decreased secretion after 2 to 3 min. In the presence of an epithelial Na(+) channel blocker, amiloride, neither carbachol nor pilocarpine affected the Na(+) level of secreted saliva; however, it significantly increased the Na(+) content of cevimeline-induced saliva. The intracellular Ca(2+) response of acinar cells was almost identical among all three agents, although recovery after drug removal was slower for cevimeline and pilocarpine. A profound decrease in intracellular pH was observed during pilocarpine and carbachol treatment, whereas intracellular acidification induced by cevimeline was only seen in the presence of a Na(+)/H(+) exchange inhibitor. When external HCO(3)(-) was removed, cevimeline-induced saliva significantly decreased. These findings suggest that cevimeline specifically activates Na(+)/H(+) exchange and may promote Na(+) reabsorption by stabilizing epithelial sodium channel activity.

  12. An exogenous hydrogen sulphide donor, NaHS, inhibits the apoptosis signaling pathway to exert cardio-protective effects in a rat hemorrhagic shock model.

    PubMed

    Xu, Yanjie; Dai, Xiongwei; Zhu, Danxia; Xu, Xiaoli; Gao, Cao; Wu, Changping

    2015-01-01

    Hydrogen sulfide (H2S) has been reported to be interwined in multiple systems, specifically in the cardiovascular system. However, the mechanisms underlying remain controversial. In the present study, we assessed the cardio-protective effects of H2S in the rat hemorrhagic shock model. Hemorrhagic shock was induced in adult male Sprague-Dawley rats by drawing blood from the femoral artery to maintain the mean arterial pressure at 35-40 mmHg for 1.5 h. The rats were assigned to four groups and the H2S donor, NaHS (28 μmol/kg, i.p.), was injected before the resuscitation in certain groups. After resuscitation the animals were observed and then killed to harvest the hearts. The morphological investigation and ultrastructural analyses were done and apoptotic cells were detected. The levels of relevant proteins were examined using Western blotting and immunohistochemical analyses. Resuscitated hemorrhagic shock induced heart injury and significantly increased the levels of serum myocardial enzymes, creatine kinase (CK) and lactate dehydrogenase (LDH) levels. Furthermore, it caused marked increase of apoptotic cells in heart tissue. Moreover, the expression of death receptor Fas and Fas-ligand, as well as the expression of apoptosis-relevant proteins active-caspase 3 and active-caspase 8 were markedly increased. Administration of NaHS significantly ameliorated hemorrhagic shock caused hemodynamic deterioration, decreased myocardial enzymes elevation, protected myocardial ultrastructure, and inhibited the expression of apoptosis-relevant proteins. It suggested that H2S might exert its cardio-protective roles via both the extrinsic Fas/FasL/caspase-8/caspase-3 pathway and the intrinsic mitochondria-involved pathways.

  13. Protective effects of vitamin B6 alone and in combination with L-cysteine and NaHS on ethanol and indomethacin-induced gastric lesions in mice.

    PubMed

    Mard, Seyyed Ali; Ashabi, Ardeshir; Badavi, Mohammad; Dianat, Mahin

    2015-03-01

    This study was undertaken to investigate the protective effects of vitamin B6, cofactor for cystathionine-γ lyase and cystathionine-β synthase (producers of H2S), alone and in combination with L-cysteine, H2S precursor, on indomethacin-, and ethanol-induced gastric lesions in male NMRI mice. Fasted male NMRI mice were randomly assigned into 12 groups (7 in each). The gastroprotective activity of vitamin B6 alone and in combination with L-cysteine and sodium hydrosulfate (NaHS) was evaluated against ethanol-, and indomethacin-induced gastric lesions. The animals were received vehicle, vitamin B6, L-cysteine, L-cysteine+vitamin B6, NaHS or NaHS+B6 before the induction of gastric lesions by ethanol (50%, 0.5 ml/25 g of body weight, orally) or indomethacin (40 mg/kg, orally). One and five hours after the administration of ethanol and indomethacin, respectively, the animals were sacrificed using anesthetics. The stomachs were removed, rinsed with normal saline and assessed for gastric wall mucus changes. Pretreatment with L-cysteine, sodium hydrosulfate, and vitamin B6 significantly decreased the total area of gastric lesions (P<0.01). The mucus production in L-cysteine-, sodium hydrosulfate-, and vitamin B6-treated animals were significantly higher than in control rats P<0.05). The gastroprotective activity of L-cysteine and sodium hydrosulfate in combination with vitamin B6 were higher than when administered alone (P<0.05). The result of this survey showed that the protective activity of L-cysteine and sodium hydrosulfate enhances in the presence of vitamin B6.

  14. Emerging roles of Na+/H+ exchangers in epilepsy and developmental brain disorders

    PubMed Central

    Falgoust, Lindsay; Pan, Jullie W.; Sun, Dandan; Zhang, Zhongling

    2016-01-01

    Epilepsy is a common central nervous system (CNS) disease characterized by recurrent transient neurological events occurring due to abnormally excessive or synchronous neuronal activity in the brain. The CNS is affected by systemic acid–base disorders, and epileptic seizures are sensitive indicators of underlying imbalances in cellular pH regulation. Na+/H+ exchangers (NHEs) are a family of membrane transporter proteins actively involved in regulating intracellular and organellar pH by extruding H+ in exchange for Na+ influx. Altering NHE function significantly influences neuronal excitability and plays a role in epilepsy. This review gives an overview of pH regulatory mechanisms in the brain with a special focus on the NHE family and the relationship between epilepsy and dysfunction of NHE isoforms. We first discuss how cells translocate acids and bases across the membrane and establish pH homeostasis as a result of the concerted effort of enzymes and ion transporters. We focus on the specific roles of the NHE family by detailing how the loss of NHE1 in two NHE mutant mice results in enhanced neuronal excitability in these animals. Furthermore, we highlight new findings on the link between mutations of NHE6 and NHE9 and developmental brain disorders including epilepsy, autism, and attention deficit hyperactivity disorder (ADHD). These studies demonstrate the importance of NHE proteins in maintaining H+ homeostasis and their intricate roles in the regulation of neuronal function. A better understanding of the mechanisms underlying NHE1, 6, and 9 dysfunctions in epilepsy formation may advance the development of new epilepsy treatment strategies. PMID:26965387

  15. Evidence that Na+/H+ exchanger 1 is an ATP-binding protein.

    PubMed

    Shimada-Shimizu, Naoko; Hisamitsu, Takashi; Nakamura, Tomoe Y; Wakabayashi, Shigeo

    2013-03-01

    Na(+)/H(+) exchanger (NHE) 1 is a member of the solute carrier superfamily, which regulates intracellular ionic homeostasis. NHE1 is known to require cellular ATP for its activity, despite there being no requirement for energy input from ATP hydrolysis. In this study, we investigated whether NHE1 is an ATP-binding protein. We designed a baculovirus vector carrying both epitope-tagged NHE1 and its cytosolic subunit CHP1, and expressed the functional NHE1-CHP1 complex on the surface of Sf9 insect cells. Using the purified complex protein consisting of NHE1 and CHP1 from Sf9 cells, we examined a photoaffinity labeling reaction with 8-azido-ATP-biotin. UV irradiation promoted the incorporation of 8-azido-ATP into NHE1, but not into CHP1, with an apparent Kd of 29.1 µM in the presence of Mg(2+). The nonlabeled nucleotides ATP, GTP, TTP and CTP all inhibited this crosslinking. However, ATP had the strongest inhibitory effect, with an apparent inhibition constant (IC50) for ATP of 2.2 mM, close to the ATP concentration giving the half-maximal activation of NHE1 activity. Importantly, crosslinking was more strongly inhibited by ATP than by ADP, suggesting that ATP is dissociated from NHE1 upon ATP hydrolysis. Limited proteolysis with thrombin and deletion mutant analysis revealed that the 8-azido-ATP-binding site is within the C-terminal cytoplasmic domain of NHE1. Equilibrium dialysis with NHE1-derived peptides provided evidence that ATP directly binds to the proximal cytoplasmic region (Gly542-Pro598), which is critical for ATP-dependent regulation of NHE1. These findings suggest that NHE1 is an ATP-binding transporter. Thus, ATP may serve as a direct activator of NHE1. © 2013 The Authors Journal compilation © 2013 FEBS.

  16. The cleaved FAS ligand activates the Na(+)/H(+) exchanger NHE1 through Akt/ROCK1 to stimulate cell motility.

    PubMed

    Monet, Michael; Poët, Mallorie; Tauzin, Sébastien; Fouqué, Amélie; Cophignon, Auréa; Lagadic-Gossmann, Dominique; Vacher, Pierre; Legembre, Patrick; Counillon, Laurent

    2016-06-15

    Transmembrane CD95L (Fas ligand) can be cleaved to release a promigratory soluble ligand, cl-CD95L, which can contribute to chronic inflammation and cancer cell dissemination. The motility signaling pathway elicited by cl-CD95L remains poorly defined. Here, we show that in the presence of cl-CD95L, CD95 activates the Akt and RhoA signaling pathways, which together orchestrate an allosteric activation of the Na(+)/H(+) exchanger NHE1. Pharmacologic inhibition of Akt or ROCK1 independently blocks the cl-CD95L-induced migration. Confirming these pharmacologic data, disruption of the Akt and ROCK1 phosphorylation sites on NHE1 decreases cell migration in cells exposed to cl-CD95L. Together, these findings demonstrate that NHE1 is a novel molecular actor in the CD95 signaling pathway that drives the cl-CD95L-induced cell migration through both the Akt and RhoA signaling pathways.

  17. The cleaved FAS ligand activates the Na+/H+ exchanger NHE1 through Akt/ROCK1 to stimulate cell motility

    PubMed Central

    Monet, Michael; Poët, Mallorie; Tauzin, Sébastien; Fouqué, Amélie; Cophignon, Auréa; Lagadic-Gossmann, Dominique; Vacher, Pierre; Legembre, Patrick; Counillon, Laurent

    2016-01-01

    Transmembrane CD95L (Fas ligand) can be cleaved to release a promigratory soluble ligand, cl-CD95L, which can contribute to chronic inflammation and cancer cell dissemination. The motility signaling pathway elicited by cl-CD95L remains poorly defined. Here, we show that in the presence of cl-CD95L, CD95 activates the Akt and RhoA signaling pathways, which together orchestrate an allosteric activation of the Na+/H+ exchanger NHE1. Pharmacologic inhibition of Akt or ROCK1 independently blocks the cl-CD95L-induced migration. Confirming these pharmacologic data, disruption of the Akt and ROCK1 phosphorylation sites on NHE1 decreases cell migration in cells exposed to cl-CD95L. Together, these findings demonstrate that NHE1 is a novel molecular actor in the CD95 signaling pathway that drives the cl-CD95L-induced cell migration through both the Akt and RhoA signaling pathways. PMID:27302366

  18. Excerpt from Medicinische Psychologie oder Physiologie der Seele by Dr Rudolph Hermann Lotze.

    PubMed

    Berrios, G E

    2005-03-01

    Hermann Lotze (1817-81) is a neglected figure in the history of psychiatry although it has been claimed that his early views were influential, for example, on the young Griesinger. Trained as a physician, psychologist and philosopher he saw better than many the impending epistemological crisis that was to affect disciplines such as psychology and medical psychology as they were being taken over by the natural sciences. The problem he endeavoured to resolve was double-headed. On the one hand, Lotze believed that the mechanisms proposed by physiology and other relevant natural sciences were essential to the explanation of human behaviour provided that its meaning and context were respected; on the other, he wanted to do away with the mysterious (metaphysical) explanations such as 'vital force' which in his time were still popular in biology. The solutions he eventually offered can understandably be seen as a weak compromise and one which statisfied no one. Materialists à outrance such as Vogt, Büchner, Lange and Ribot though he was too 'metaphysical'; spiritualist philosophers believed that he had surrendered too much to biology. It is likely that Lotze remained, in fact, a metaphysician as can be ascertained by studying his concept of Seele (soul, mind) into which he packed enough furniture to make many believe that he was an idealist thinker. This paper discusses some of these issues and justifies the choice of classic text, namely, Lotze's illuminating Introduction to his book Medicinische Psychologie oder Physiologie der Seele.

  19. Inhibition of Na+/H+ exchanger 1 by cariporide reduces burn-induced intestinal barrier breakdown.

    PubMed

    Yang, Xuekang; Chen, Ji; Bai, Hua; Tao, Ke; Zhou, Qin; Hou, Hongyi; Hu, Dahai

    2013-12-01

    Severe burns initiate an inflammatory cascade within the gut, which leads to intestinal mucosal injury. Although Na(+)/H(+) exchanger 1 (NHE1) is recognised as a pivotal player in several inflammatory processes, its role in burn-induced intestinal injury is relatively unknown. We hypothesised that NHE1 might be involved in the increased intestinal permeability and barrier breakdown after severe burns. Thus, we here investigate whether the inhibition of NHE1 has a protective effect on burn-induced intestinal injury. Mice were subjected to a 30% total body surface area (TBSA) full-thickness steam burn. Cariporide was used to assess the function of NHE1 in mice with burn-induced intestinal injury by fluorescence spectrophotometry, Western blotting and enzyme linked immunosorbent assay (ELISA). We found that severe burn increased intestinal permeability, associated with the up-regulation of NHE1 and raised inflammatory cytokine levels. Mice treated with the NHE1 inhibitor cariporide had significantly attenuated burn-induced intestinal permeability and a reduced inflammatory response. NHE1 inhibition also reduced nuclear factor-κB (NF-κB) activation and attenuated p38 mitogen-activated protein kinase (MAPK) phosphorylation. Our study suggests that NHE1 plays an important role in burn-induced intestinal permeability through the regulation of the inflammatory response. Inhibition of NHE1 may be adopted as a potential therapeutic strategy for attenuating intestinal barrier breakdown. Copyright © 2013 Elsevier Ltd and ISBI. All rights reserved.

  20. A neural network potential energy surface for the NaH2 system and dynamics studies on the H(2S) + NaH(X1Σ+) → Na(2S) + H2(X1Σg+) reaction.

    PubMed

    Wang, Shufen; Yuan, Jiuchuang; Li, Huixing; Chen, Maodu

    2017-08-02

    In order to study the dynamics of the reaction H( 2 S) + NaH(X 1 Σ + ) → Na( 2 S) + H 2 (X 1 Σ g + ), a new potential energy surface (PES) for the ground state of the NaH 2 system is constructed based on 35 730 ab initio energy points. Using basis sets of quadruple zeta quality, multireference configuration interaction calculations with Davidson correction were carried out to obtain the ab initio energy points. The neural network method is used to fit the PES, and the root mean square error is very small (0.00639 eV). The bond lengths, dissociation energies, zero-point energies and spectroscopic constants of H 2 (X 1 Σ g + ) and NaH(X 1 Σ + ) obtained on the new NaH 2 PES are in good agreement with the experiment data. On the new PES, the reactant coordinate-based time-dependent wave packet method is applied to study the reaction dynamics of H( 2 S) + NaH(X 1 Σ + ) → Na( 2 S) + H 2 (X 1 Σ g + ), and the reaction probabilities, integral cross-sections (ICSs) and differential cross-sections (DCSs) are obtained. There is no threshold in the reaction due to the absence of an energy barrier on the minimum energy path. When the collision energy increases, the ICSs decrease from a high value at low collision energy. The DCS results show that the angular distribution of the product molecules tends to the forward direction. Compared with the LiH 2 system, the NaH 2 system has a larger mass and the PES has a larger well at the H-NaH configuration, which leads to a higher ICS value in the H( 2 S) + NaH(X 1 Σ + ) → Na( 2 S) + H 2 (X 1 Σ g + ) reaction. Because the H( 2 S) + NaH(X 1 Σ + ) → Na( 2 S) + H 2 (X 1 Σ g + ) reaction releases more energy, the product molecules can be excited to a higher vibrational state.

  1. Expression of Na(+)/H(+) exchanger isoforms 1, 2, 3, and 4 in bovine endometrium and the influence of uterine pH at time of fixed-time AI of pregnancy success.

    PubMed

    Bolzenius, Jennifer K; Cushman, Robert A; Perry, George A

    2016-08-01

    Cows that exhibit estrus prior to fixed-time AI had increased sperm transport to the site of fertilization, and improved embryo quality on d 6 after insemination. Sperm transport is influenced by uterine pH, and research has reported that uterine pH decreased at onset of estrus, but must return to normal prior to ovulation. Therefore, the objectives of these studies were to investigate a possible mechanism for the regulation of uterine pH around the onset of estrus, and to determine if uterine pH at time of fixed-time AI influenced pregnancy success. In experiment 1, Angus-cross beef cows (n=40 and 28 in rep. 1 and 2, respectively) were synchronized with the PG 6-day CIDR protocol (PGF2α on d -9, GnRH and insertion of a CIDR on d -6, and PGF2α and CIDR removal on d 0). Cows were blocked by follicle size at time of CIDR removal, and uterine biopsies were collected at 0, 12, 24, 36, 48, 60 (Rep. 1), 72, 84, or 96h (Rep2) after CIDR removal, and total cellular RNA was extracted from all biopsies. Estrus was monitored by the HeatWatch Estrous Detection System. In experiment 2, 223 postpartum beef cows in 2 herds were synchronized with a fixed-time AI protocol (herd 1: n=97; CO-Synch plus CIDR protocol; herd 2: n=126; Co-synch protocol). Uterine pH was determined at time of AI (n=80 and 63 for herd 1 and 2, respectively), and estrus was monitored by visual estrus detection with the aid of an ESTROTECT estrous detection patches, and pregnancy was determined by transrectal ultrasonography. In experiment 1, there was a significant (P<0.01), quadratic relationship in expression of Na(+)/H(+) exchanger isoforms 1, 2, and 3 among animals that exhibited estrus, with expression greatest at time of CIDR removal, decreasing to the onset of estrus, and then increasing again following the onset of estrus. Among cows that did not exhibit estrus, the preceding relationship did not exist (P>0.46). In experiment 2, cows that had initiated estrus prior to fixed-time AI had decreased

  2. Regulation of intracellular pH in LLC-PK1 cells by Na+/H+ exchange.

    PubMed

    Montrose, M H; Murer, H

    1986-01-01

    Suspensions of LLC-PK1 cells (a continuous epitheliod cell line with renal characteristics) are examined for mechanisms of intracellular pH regulation using the fluorescent probe BCECF. Initial experiments determine suitable calibration procedures for use of the BCECF fluorescent signal. They also determine that the cell suspension contains cells which (after 4 hr in suspension) have Na+ and K+ gradients comparable to those of cells in monolayer culture. The steady-state intracellular pH (7.05 +/- 0.01, n = 5) of cells which have recovered in (pH 7.4) Na+-containing medium is not affected over several minutes by addition of 100 microM amiloride or removal of extracellular Na+ (Na+o less than 1 mM). In contrast, when the cells recover from an acid load (caused by NH4 preincubation and removal), the recovery is largely Na+ dependent and is sensitive to 100 microM amiloride. These results suggest that with resting pH near neutrality, both Na+o/H+i and Na+i/H+o exchange reactions are functionally inactive (compared to cellular buffering capacity). In contrast, Na+o/H+i exchange is activated by an increased cellular acid load. This activation may be observed directly either as a stimulation of net H+ efflux or net Na+ influx with decreasing intracellular pH. The extrapolation of this latter data suggests a "set point" of Na+/H+ exchange of approximately pH 7.0, consistent with the observed resting intracellular pH of approximately 7.05.

  3. Functional characterization of Na(+)/H(+) exchangers in primary cultures of prairie dog gallbladder.

    PubMed

    Narins, S C; Park, E H; Ramakrishnan, R; Garcia, F U; Diven, J N; Balin, B J; Hammond, C J; Sodam, B R; Smith, P R; Abedin, M Z

    2004-01-15

    Gallbladder Na(+) absorption is linked to gallstone formation in prairie dogs. We previously reported Na(+)/H(+) exchanger (NHE1-3) expression in native gallbladder tissues. Here we report the functional characterization of NHE1, NHE2 and NHE3 in primary cultures of prairie dog gallbladder epithelial cells (GBECs). Immunohistochemical studies showed that GBECs grown to confluency are homogeneous epithelial cells of gastrointestinal origin. Electron microscopic analysis of GBECs demonstrated that the cells form polarized monolayers characterized by tight junctions and apical microvilli. GBECs grown on Snapwells exhibited polarity and developed transepithelial short-circuit current, I(sc), (11.6 +/- 0.5 microA. cm(-2)), potential differences, V(t) (2.1 +/- 0.2 mV), and resistance, R(t) (169 +/- 12 omega. cm(2)). NHE activity in GBECs assessed by measuring dimethylamiloride-inhibitable (22)Na(+) uptake under a H(+) gradient was the same whether grown on permeable Snapwells or plastic wells. The basal rate of (22)Na(+) uptake was 21.4 +/- 1.3 nmol x mg prot(-1) x min(-1), of which 9.5 +/- 0.7 (approximately 45%) was mediated through apically-restricted NHE. Selective inhibition with HOE-694 revealed that NHE1, NHE2 and NHE3 accounted for approximately 6%, approximately 66% and approximately 28% of GBECs' total NHE activity, respectively. GBECs exhibited saturable NHE kinetics ( V(max) 9.2 +/- 0.3 nmol x mg prot(-1) x min(-1); K(m) 11.4 +/- 1.4 m M Na(+)). Expression of NHE1, NHE2 and NHE3 mRNAs was confirmed by RT-PCR analysis. These results demonstrate that the primary cultures of GBECs exhibit Na(+) transport characteristics similar to native gallbladder tissues, suggesting that these cells can be used as a tool for studying the mechanisms of gallbladder ion transport both under physiologic conditions and during gallstone formation.

  4. Combined Therapy of Septicemia with Ofloxacin and/or Synthetic Trehalose Dicorynomycolate (S-TDCM) in Irradiated and Wounded Mice (Die Kombinierte Therapie der Septikaemie mit Ofloxacin und/oder Synthetischem Trehalose- Dicorynomycolat (S-TDCM) bei Bestrahlten und Verwundeten Maeusen)

    DTIC Science & Technology

    1989-01-01

    COMBINED THERAPY OF SEPTICEMIA WITH OFLOXACIN AND/OR SYNTHETIC TREHALOSE DICORYNOMYCOLATE (S-TDCM)IN IRRADIATED AND WOUNDED MICE * DIE KOMBINIERTE THERAPIE...DER SEPTIKAMIE MIT OFLOXACIN UND ’ODER SYNTHETISCHEM TREHALOSE -DICORYNOMYCOLAT (S-TDCM) BEI BESTRAHLTEN UND VERWUNDETEN MAUSEN GARY S. M4ADONNA. MARY...ceptibility to bacterial infection from either endogenous or exogenous origin. Treatment with ofloxacin or synthetic trehalose dicorynemycolate (S

  5. Flow cytometric kinetic assay of the activity of Na+/H+ antiporter in mammalian cells.

    PubMed

    Dolz, María; O'Connor, José-Enrique; Lequerica, Juan L

    2004-10-01

    The Na(+)/H(+) exchanger (NHE) of mammalian cells is an integral membrane protein that extrudes H(+) ion in exchange for extracellular Na(+) and plays a crucial role in the regulation of intracellular pH (pHi). Thus, when pHi is lowered, NHE extrudes protons at a rate depending of pHi that can be expressed as pH units/s. To abolish the activity of other cellular pH-restoring systems, cells were incubated in bicarbonate-free Dulbecco's modified Eagle's medium buffered with HEPES. Flow cytometry was used to determine pHi with 2',7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein acetoxymethyl ester or 5-(and-6)-carboxy SNARF-1 acetoxymethyl ester acetate, and the appropriate fluorescence ratios were measured. The calibration of fluorescence ratios versus pHi was established by using ionophore nigericin. The activity of NHE was calculated by a kinetic flow cytometric assay as the slope at time 0 of the best-fit curve of pHi recovery versus time after intracellular acidification with a pulse of exogenous sodium propionate. The kinetic method allowed determination of the pHi-dependent activity of NHE in cell lines and primary cell cultures. NHE activity values were demonstrated to be up to 0.016 pH units/s within the pHi range of 7.3 to 6.3. The inhibition of NHE activity by the specific inhibitor ethyl isopropyl amiloride was easily detected by this method. The assay conditions can be used to relate variations in pHi with the activity of NHE and provide a standardized method to compare between different cells, inhibitors, models of ischemia by acidification, and other relevant experimental or clinical situations.

  6. Differential Association of the Na+/H+ Exchanger Regulatory Factor (NHERF) Family of Adaptor Proteins with the Raft-and the Non-Raft Brush Border Membrane Fractions of NHE3

    PubMed Central

    Sultan, Ayesha; Luo, Min; Yu, Qin; Riederer, Brigitte; Xia, Weiliang; Chen, Mingmin; Lissner, Simone; Gessner, Johannes E.; Donowitz, Mark; Yun, C. Chris; deJonge, Hugo; Lamprecht, Georg; Seidler, Ursula

    2014-01-01

    Background/Aims Trafficking, brush border membrane (BBM) retention, and signal-specific regulation of the Na+/H+ exchanger NHE3 is regulated by the Na+/H+ Exchanger Regulatory Factor (NHERF) family of PDZ-adaptor proteins, which enable the formation of multiprotein complexes. It is unclear, however, what determines signal specificity of these NHERFs. Thus, we studied the association of NHE3, NHERF1 (EBP50), NHERF2 (E3KARP), and NHERF3 (PDZK1) with lipid rafts in murine small intestinal BBM. Methods Detergent resistant membranes (“lipid rafts”) were isolated by floatation of Triton X-incubated small intestinal BBM from a variety of knockout mouse strains in an Optiprep step gradient. Acid-activated NHE3 activity was measured fluorometrically in BCECF-loaded microdissected villi, or by assessment of CO2/HCO3− mediated increase in fluid absorption in perfused jejunal loops of anethetized mice. Results NHE3 was found to partially associate with lipid rafts in the native BBM, and NHE3 raft association had an impact on NHE3 transport activity and regulation in vivo. NHERF1, 2 and 3 were differentially distributed to rafts and non-rafts, with NHERF2 being most raft-associated and NHERF3 entirely non-raft associated. NHERF2 expression enhanced the localization of NHE3 to membrane rafts. The use of acid sphingomyelinase-deficient mice, which have altered membrane lipid as well as lipid raft composition, allowed us to test the validity of the lipid raft concept in vivo. Conclusions The differential association of the NHERFs with the raft-associated and the non-raft fraction of NHE3 in the brush border membrane is one component of the differential and signal-specific NHE3 regulation by the different NHERFs. PMID:24297041

  7. Differential association of the Na+/H+ Exchanger Regulatory Factor (NHERF) family of adaptor proteins with the raft- and the non-raft brush border membrane fractions of NHE3.

    PubMed

    Sultan, Ayesha; Luo, Min; Yu, Qin; Riederer, Brigitte; Xia, Weiliang; Chen, Mingmin; Lissner, Simone; Gessner, Johannes E; Donowitz, Mark; Yun, C Chris; deJonge, Hugo; Lamprecht, Georg; Seidler, Ursula

    2013-01-01

    Trafficking, brush border membrane (BBM) retention, and signal-specific regulation of the Na+/H+ exchanger NHE3 is regulated by the Na+/H+ Exchanger Regulatory Factor (NHERF) family of PDZ-adaptor proteins, which enable the formation of multiprotein complexes. It is unclear, however, what determines signal specificity of these NHERFs. Thus, we studied the association of NHE3, NHERF1 (EBP50), NHERF2 (E3KARP), and NHERF3 (PDZK1) with lipid rafts in murine small intestinal BBM. Detergent resistant membranes ("lipid rafts") were isolated by floatation of Triton X-incubated small intestinal BBM from a variety of knockout mouse strains in an Optiprep step gradient. Acid-activated NHE3 activity was measured fluorometrically in BCECF-loaded microdissected villi, or by assessment of CO2/HCO3(-) mediated increase in fluid absorption in perfused jejunal loops of anethetized mice. NHE3 was found to partially associate with lipid rafts in the native BBM, and NHE3 raft association had an impact on NHE3 transport activity and regulation in vivo. NHERF1, 2 and 3 were differentially distributed to rafts and non-rafts, with NHERF2 being most raft-associated and NHERF3 entirely non-raft associated. NHERF2 expression enhanced the localization of NHE3 to membrane rafts. The use of acid sphingomyelinase-deficient mice, which have altered membrane lipid as well as lipid raft composition, allowed us to test the validity of the lipid raft concept in vivo. The differential association of the NHERFs with the raft-associated and the non-raft fraction of NHE3 in the brush border membrane is one component of the differential and signal-specific NHE3 regulation by the different NHERFs. © 2013 S. Karger AG, Basel.

  8. Glioma-mediated microglial activation promotes glioma proliferation and migration: roles of Na+/H+ exchanger isoform 1

    PubMed Central

    Zhu, Wen; Carney, Karen E.; Pigott, Victoria M.; Falgoust, Lindsay M.; Clark, Paul A.; Kuo, John S.; Sun, Dandan

    2016-01-01

    Microglia play important roles in extracellular matrix remodeling, tumor invasion, angiogenesis, and suppression of adaptive immunity in glioma. Na+/H+ exchanger isoform 1 (NHE1) regulates microglial activation and migration. However, little is known about the roles of NHE1 in intratumoral microglial activation and microglia–glioma interactions. Our study revealed up-regulation of NHE1 protein expression in both glioma cells and tumor-associated Iba1+ microglia in glioma xenografts and glioblastoma multiforme microarrays. Moreover, we observed positive correlation of NHE1 expression with Iba1 intensity in microglia/macrophages. Glioma cells, via conditioned medium or non-contact glioma-microglia co-cultures, concurrently upregulated microglial expression of NHE1 protein and other microglial activation markers (iNOS, arginase-1, TGF-β, IL-6, IL-10 and the matrix metalloproteinases MT1-MMP and MMP9). Interestingly, glioma-stimulated microglia reciprocally enhanced glioma proliferation and migration. Most importantly, inhibition of microglial NHE1 activity via small interfering RNA (siRNA) knockdown or the potent NHE1-specific inhibitor HOE642 significantly attenuated microglial activation and abolished microglia-stimulated glioma migration and proliferation. Taken together, our findings provide the first evidence that NHE1 function plays an important role in glioma–microglia interactions, enhancing glioma proliferation and invasion by stimulating microglial release of soluble factors. NHE1 upregulation is a novel marker of the glioma-associated microglial activation phenotype. Inhibition of NHE1 represents a novel glioma therapeutic strategy by targeting tumor-induced microglial activation. PMID:27287871

  9. Inhibition of Na+/H+ Exchanger Isoform 1 Is Neuroprotective in Neonatal Hypoxic Ischemic Brain Injury

    PubMed Central

    Kleman, Neil; Uluc, Kutluay; Kendigelen, Pinar; Hagemann, Tracy; Akture, Erinc; Messing, Albee; Ferrazzano, Peter; Sun, Dandan

    2011-01-01

    Abstract We investigated the role of Na+/H+ exchanger isoform 1 (NHE-1) in neonatal hypoxia/ischemia (HI). HI was induced by unilateral ligation of the left common carotid artery in postnatal day 9 (P9) mice, and subsequent exposure of animals to 8% O2 for 55 min. A pre/posttreatment group received a selective and potent NHE-1 inhibitor HOE 642 (0.5 mg/kg, intraperitoneally) 5 min before HI, then at 24 and 48 h after HI. A posttreatment group received HOE 642 (0.5 mg/kg) at 10 min, 24 h, and 48 h after HI. Saline injections were used as vehicle controls. The vehicle-control brains at 72 h after HI exhibited neuronal degeneration in the ipsilateral hippocampus, striatum, and thalamus, as identified with Fluoro-Jade C positive staining and loss of microtubule-associated protein 2 (MAP2) expression. NHE-1 protein was upregulated in glial fibrillary acidic protein–positive reactive astrocytes. In HOE 642–treated brains, the morphologic hippocampal structures were better preserved and displayed less neurodegeneration and a higher level of MAP2 expression. Motor-learning deficit was detected at 4 weeks of age after HI in the vehicle control group. Inhibition of NHE-1 in P9 mice not only reduced neurodegeneration during the acute stage of HI but also improved the striatum-dependent motor learning and spatial learning at 8 weeks of age after HI. These findings suggest that NHE-1–mediated disruption of ionic homeostasis contributes to striatal and CA1 pyramidal neuronal injury after neonatal HI. Antioxid. Redox Signal. 14, 1803–1813. PMID:20712402

  10. Molecular detection and immunological localization of gill Na+/H+ exchanger in the dogfish (Squalus acanthias).

    PubMed

    Claiborne, James B; Choe, Keith P; Morrison-Shetlar, Alison I; Weakley, Jill C; Havird, Justin; Freiji, Abe; Evans, David H; Edwards, Susan L

    2008-03-01

    The dogfish (Squalus acanthias) can make rapid adjustments to gill acid-base transfers to compensate for internal acidosis/alkalosis. Branchial Na+/H+ exchange (NHE) has been postulated as one mechanism driving the excretion of H+ following acidosis. We have cloned gill cDNA that includes an open reading frame coding for a 770-residue protein most homologous (approximately 71%) to mammalian NHE2. RT-PCR revealed NHE2 transcripts predominantly in gill, stomach, rectal gland, intestine, and kidney. In situ hybridization with an antisense probe against NHE2 in gill sections revealed a strong mRNA signal from a subset of interlamellar and lamellae cells. We developed dogfish-specific polyclonal antibodies against NHE2 that detected a approximately 70-kDa protein in Western blots and immunologically recognized branchial cells having two patterns of protein expression. Cytoplasmic and apical NHE2 immunoreactivity were observed in cells coexpressing basolateral Na+-K+-ATPase. Other large ovoid cells more generally staining for NHE2 also were strongly positive for basolateral H+-ATPase. Gill mRNA levels for NHE2 and H+-ATPase did not change following systemic acidosis (as measured by quantitative PCR 2 h after a 1- or 2-meq/kg acid infusion). These data indicate that posttranslational adjustments of NHE2 and other transport systems (e.g., NHE3) following acidosis may be of importance in the short-term pH adjustment and net branchial H+ efflux observed in vivo. NHE2 may play multiple roles in the gills, involved with H+ efflux from acid-secreting cells, basolateral H+ reabsorption for pHi regulation, and in parallel with H+-ATPase for the generation of HCO3(-) in base-secreting cells.

  11. Herpes simplex virus internalization into epithelial cells requires Na+/H+ exchangers and p21-activated kinases but neither clathrin- nor caveolin-mediated endocytosis.

    PubMed

    Devadas, Deepika; Koithan, Thalea; Diestel, Randi; Prank, Ute; Sodeik, Beate; Döhner, Katinka

    2014-11-01

    Herpes simplex virus 1 (HSV-1) is an alphaherpesvirus that has been reported to infect some epithelial cell types by fusion at the plasma membrane but others by endocytosis. To determine the molecular mechanisms of productive HSV-1 cell entry, we perturbed key endocytosis host factors using specific inhibitors, RNA interference (RNAi), or overexpression of dominant negative proteins and investigated their effects on HSV-1 infection in the permissive epithelial cell lines Vero, HeLa, HEp-2, and PtK2. HSV-1 internalization required neither endosomal acidification nor clathrin- or caveolin-mediated endocytosis. In contrast, HSV-1 gene expression and internalization were significantly reduced after treatment with 5-(N-ethyl-N-isopropyl)amiloride (EIPA). EIPA blocks the activity of Na(+)/H(+) exchangers, which are plasma membrane proteins implicated in all forms of macropinocytosis. HSV-1 internalization furthermore required the function of p21-activated kinases that contribute to macropinosome formation. However, in contrast to some forms of macropinocytosis, HSV-1 did not enlist the activities of protein kinase C (PKC), tyrosine kinases, C-terminal binding protein 1, or dynamin to activate its internalization. These data suggest that HSV-1 depends on Na(+)/H(+) exchangers and p21-activated kinases either for macropinocytosis or for local actin rearrangements required for fusion at the plasma membrane or subsequent passage through the actin cortex underneath the plasma membrane. After initial replication in epithelial cells, herpes simplex viruses (HSVs) establish latent infections in neurons innervating these regions. Upon primary infection and reactivation from latency, HSVs cause many human skin and neurological diseases, particularly in immunocompromised hosts, despite the availability of effective antiviral drugs. Many viruses use macropinocytosis for virus internalization, and many host factors mediating this entry route have been identified, although the

  12. Drug Transporters and Na+/H+ Exchange Regulatory Factor PSD-95/Drosophila Discs Large/ZO-1 Proteins

    PubMed Central

    Walsh, Dustin R.; Nolin, Thomas D.

    2015-01-01

    Drug transporters govern the absorption, distribution, and elimination of pharmacologically active compounds. Members of the solute carrier and ATP binding-cassette drug transporter family mediate cellular drug uptake and efflux processes, thereby coordinating the vectorial movement of drugs across epithelial barriers. To exert their physiologic and pharmacological function in polarized epithelia, drug transporters must be targeted and stabilized to appropriate regions of the cell membrane (i.e., apical versus basolateral). Despite the critical importance of drug transporter membrane targeting, the mechanisms that underlie these processes are largely unknown. Several clinically significant drug transporters possess a recognition sequence that binds to PSD-95/Drosophila discs large/ZO-1 (PDZ) proteins. PDZ proteins, such as the Na+/H+ exchanger regulatory factor (NHERF) family, act to stabilize and organize membrane targeting of multiple transmembrane proteins, including many clinically relevant drug transporters. These PDZ proteins are normally abundant at apical membranes, where they tether membrane-delimited transporters. NHERF expression is particularly high at the apical membrane in polarized tissue such as intestinal, hepatic, and renal epithelia, tissues important to drug disposition. Several recent studies have highlighted NHERF proteins as determinants of drug transporter function secondary to their role in controlling membrane abundance and localization. Mounting evidence strongly suggests that NHERF proteins may have clinically significant roles in pharmacokinetics and pharmacodynamics of several pharmacologically active compounds and may affect drug action in cancer and chronic kidney disease. For these reasons, NHERF proteins represent a novel class of post-translational mediators of drug transport and novel targets for new drug development. PMID:26092975

  13. Diversities and similarities in pH dependency among bacterial NhaB-like Na+/H+ antiporters.

    PubMed

    Kiriyama, Wakako; Honma, Kei; Hiratsuka, Tomoaki; Takahashi, Itsuka; Nomizu, Takahiro; Takashima, Yuta; Ohtsuka, Masataka; Takahashi, Daiki; Moriyama, Kazuya; Mori, Sayoko; Nishiyama, Shiho; Fukuhara, Masahiro; Nakamura, Tatsunosuke; Shigematsu, Toru; Yamaguchi, Toshio

    2013-10-01

    NhaB-like antiporters were the second described class of Na(+)/H(+) antiporters, identified in bacteria more than 20 years ago. While nhaB-like gene sequences have been found in a number of bacterial genomes, only a few of the NhaB-like antiporters have been functionally characterized to date. Although earlier studies have identified a few pH-sensitive and -insensitive NhaB-like antiporters, the mechanisms that determine their pH responses still remain elusive. In this study, we sought to investigate the diversities and similarities among bacterial NhaB-like antiporters, with particular emphasis on their pH responsiveness. Our phylogenetic analysis of NhaB-like antiporters, combined with pH profile analyses of activities for representative members of several phylogenetic groups, demonstrated that NhaB-like antiporters could be classified into three distinct types according to the degree of their pH dependencies. Interestingly, pH-insensitive NhaB-like antiporters were only found in a limited proportion of enterobacterial species, which constitute a subcluster that appears to have diverged relatively recently among enterobacterial NhaB-like antiporters. Furthermore, kinetic property analyses of NhaB-like antiporters at different pH values revealed that the degree of pH sensitivity of antiport activities was strongly correlated with the magnitude of pH-dependent change in apparent Km values, suggesting that the dramatic pH sensitivities observed for several NhaB-like antiporters might be mainly due to the significant increases of apparent Km at lower pH. These results strongly suggested the possibility that the loss of pH sensitivity of NhaB-like antiporters had occurred relatively recently, probably via accumulation of the mutations that impair pH-dependent change of Km in the course of molecular evolution.

  14. Endogenous flow-induced superoxide stimulates Na/H exchange activity via PKC in thick ascending limbs

    PubMed Central

    Garvin, Jeffrey L.

    2014-01-01

    Luminal flow stimulates Na reabsorption along the nephron and activates protein kinase C (PKC) which enhances endogenous superoxide (O2−) production by thick ascending limbs (TALs). Exogenously-added O2− augments TAL Na reabsorption, a process also dependent on PKC. Luminal Na/H exchange (NHE) mediates NaHCO3 reabsorption. However, whether flow-stimulated, endogenously-produced O2− enhances luminal NHE activity and the signaling pathway involved are unclear. We hypothesized that flow-induced production of endogenous O2− stimulates luminal NHE activity via PKC in TALs. Intracellular pH recovery was measured as an indicator of NHE activity in isolated, perfused rat TALs. Increasing luminal flow from 5 to 20 nl/min enhanced total NHE activity from 0.104 ± 0.031 to 0.167 ± 0.036 pH U/min, 81%. The O2− scavenger tempol decreased total NHE activity by 0.066 ± 0.011 pH U/min at 20 nl/min but had no significant effect at 5 nl/min. With the NHE inhibitor EIPA in the bath to block basolateral NHE, tempol reduced flow-enhanced luminal NHE activity by 0.029 ± 0.010 pH U/min, 30%. When experiments were repeated with staurosporine, a nonselective PKC inhibitor, tempol had no effect. Because PKC could mediate both induction of O2− by flow and the effect of O2− on luminal NHE activity, we used hypoxanthine/xanthine oxidase to elevate O2−. Hypoxanthine/xanthine oxidase increased luminal NHE activity by 0.099 ± 0.020 pH U/min, 137%. Staurosporine and the PKCα/β1-specific inhibitor Gö6976 blunted this effect. We conclude that flow-induced O2− stimulates luminal NHE activity in TALs via PKCα/β1. This accounts for part of flow-stimulated bicarbonate reabsorption by TALs. PMID:25080525

  15. New naphthalene whole-cell bioreporter for measuring and assessing naphthalene in polycyclic aromatic hydrocarbons contaminated site.

    PubMed

    Sun, Yujiao; Zhao, Xiaohui; Zhang, Dayi; Ding, Aizhong; Chen, Cheng; Huang, Wei E; Zhang, Huichun

    2017-11-01

    A new naphthalene bioreporter was designed and constructed in this work. A new vector, pWH1274_Nah, was constructed by the Gibson isothermal assembly fused with a 9 kb naphthalene-degrading gene nahAD (nahAa nahAb nahAc nahAd nahB nahF nahC nahQ nahE nahD) and cloned into Acinetobacter ADPWH_lux as the host, capable of responding to salicylate (the central metabolite of naphthalene). The ADPWH_Nah bioreporter could effectively metabolize naphthalene and evaluate the naphthalene in natural water and soil samples. This whole-cell bioreporter did not respond to other polycyclic aromatic hydrocarbons (PAHs; pyrene, anthracene, and phenanthrene) and demonstrated a positive response in the presence of 0.01 μM naphthalene, showing high specificity and sensitivity. The bioluminescent response was quantitatively measured after a 4 h exposure to naphthalene, and the model simulation further proved the naphthalene metabolism dynamics and the salicylate-activation mechanisms. The ADPWH_Nah bioreporter also achieved a rapid evaluation of the naphthalene in the PAH-contaminated site after chemical spill accidents, showing high consistency with chemical analysis. The engineered Acinetobacter variant had significant advantages in rapid naphthalene detection in the laboratory and potential in situ detection. The state-of-the-art concept of cloning PAHs-degrading pathway in salicylate bioreporter hosts led to the construction and assembly of high-throughput PAH bioreporter array, capable of crude oil contamination assessment and risk management. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Compensatory regulation of Na+ absorption by Na+/H+ exchanger and Na+-Cl- cotransporter in zebrafish (Danio rerio)

    PubMed Central

    2013-01-01

    Introduction In mammals, internal Na+ homeostasis is maintained through Na+ reabsorption via a variety of Na+ transport proteins with mutually compensating functions, which are expressed in different segments of the nephrons. In zebrafish, Na+ homeostasis is achieved mainly through the skin/gill ionocytes, namely Na+/H+ exchanger (NHE3b)-expressing H+-ATPase rich (HR) cells and Na+-Cl- cotransporter (NCC)-expressing NCC cells, which are functionally homologous to mammalian proximal and distal convoluted tubular cells, respectively. The present study aimed to investigate whether or not the functions of HR and NCC ionocytes are differentially regulated to compensate for disruptions of internal Na+ homeostasis and if the cell differentiation of the ionocytes is involved in this regulation pathway. Results Translational knockdown of ncc caused an increase in HR cell number and a resulting augmentation of Na+ uptake in zebrafish larvae, while NHE3b loss-of-function caused an increase in NCC cell number with a concomitant recovery of Na+ absorption. Environmental acid stress suppressed nhe3b expression in HR cells and decreased Na+ content, which was followed by up-regulation of NCC cells accompanied by recovery of Na+ content. Moreover, knockdown of ncc resulted in a significant decrease of Na+ content in acid-acclimated zebrafish. Conclusions These results provide evidence that HR and NCC cells exhibit functional redundancy in Na+ absorption, similar to the regulatory mechanisms in mammalian kidney, and suggest this functional redundancy is a critical strategy used by zebrafish to survive in a harsh environment that disturbs body fluid Na+ homeostasis. PMID:23924428

  17. Gene inactivation of Na+/H+ exchanger isoform 1 attenuates apoptosis and mitochondrial damage following transient focal cerebral ischemia

    PubMed Central

    Wang, Yanping; Luo, Jing; Chen, Xinzhi; Chen, Hai; Cramer, Sam W.; Sun, Dandan

    2010-01-01

    We investigated mechanisms underlying the Na+/H+ exchanger isoform 1 (NHE1)-mediated neuronal damage in transient focal ischemia. Physiological parameters, body and tympanic temperatures, and regional cerebral blood flow during 30 min middle cerebral artery occlusion (MCAO) were similar in wild-type NHE1 (NHE1+/+) and NHE1 heterozygous (NHE1+/−) mice. NHE1+/+ mice developed infarct volume of 57.3 ± 8.8 mm3 at 24 h reperfusion (Rp), which progressed to 86.1 ± 10.0 mm3 at 72 h Rp. This delayed cell death was preceded by release of mitochondrial cytochrome c (Cyt. C), nuclear translocation of apoptosis-inducing factor (AIF), activation of caspase-3, and TUNEL-positive staining and chromatin condensation in the ipsilateral hemispheres of NHE1+/+ brains. In contrast, NHE1+/− mice had a significantly smaller infarct volume and improved neurological function. A similar neuroprotection was obtained with NHE1 inhibitor HOE 642. The number of apoptotic cells, release of AIF and Cyt. C or levels of active caspase-3 was significantly reduced in NHE1+/− brains. These data imply that NHE1 activity may contribute to ischemic apoptosis. Ischemic brains did not exhibit changes of NHE1 protein expression. In contrast, up-regulation of NHE1 expression was found in NHE1+/+ neurons after in vitro ischemia. These data suggest that NHE1 activation following cerebral ischemia contributes to mitochondrial damage and ischemic apoptosis. PMID:18662334

  18. Endosomal acidification by Na+/H+ exchanger NHE5 regulates TrkA cell-surface targeting and NGF-induced PI3K signaling

    PubMed Central

    Diering, Graham H.; Numata, Yuka; Fan, Steven; Church, John; Numata, Masayuki

    2013-01-01

    To facilitate polarized vesicular trafficking and signal transduction, neuronal endosomes have evolved sophisticated mechanisms for pH homeostasis. NHE5 is a member of the Na+/H+ exchanger family and is abundantly expressed in neurons and associates with recycling endosomes. Here we show that NHE5 potently acidifies recycling endosomes in PC12 cells. NHE5 depletion by plasmid-based short hairpin RNA significantly reduces cell surface abundance of TrkA, an effect similar to that observed after treatment with the V-ATPase inhibitor bafilomycin. A series of cell-surface biotinylation experiments suggests that anterograde trafficking of TrkA from recycling endosomes to plasma membrane is the likeliest target affected by NHE5 depletion. NHE5 knockdown reduces phosphorylation of Akt and Erk1/2 and impairs neurite outgrowth in response to nerve growth factor (NGF) treatment. Of interest, although both phosphoinositide 3-kinase–Akt and Erk signaling are activated by NGF-TrkA, NGF-induced Akt-phosphorylation appears to be more sensitively affected by perturbed endosomal pH. Furthermore, NHE5 depletion in rat cortical neurons in primary culture also inhibits neurite formation. These results collectively suggest that endosomal pH modulates trafficking of Trk-family receptor tyrosine kinases, neurotrophin signaling, and possibly neuronal differentiation. PMID:24006492

  19. Azilsartan Improves Salt Sensitivity by Modulating the Proximal Tubular Na+-H+ Exchanger-3 in Mice.

    PubMed

    Hatanaka, Masaki; Kaimori, Jun-Ya; Yamamoto, Satoko; Matsui, Isao; Hamano, Takayuki; Takabatake, Yoshitsugu; Ecelbarger, Carolyn M; Takahara, Shiro; Isaka, Yoshitaka; Rakugi, Hiromi

    2016-01-01

    A potent angiotensin II type-1 receptor blocker, azilsartan, has been reported to reduce blood pressure more effectively than candesartan. Interestingly, azilsartan can also restore the circadian rhythm of blood pressure. We hypothesized that azilsartan could also improve salt sensitivity; thus, we examined the effect of azilsartan on sodium handling in renal tubules. Subtotal nephrectomized C57BL/6 mice received azilsartan (1.0 mg/kg/day), candesartan (0.3 mg/kg/day), or vehicle via the oral route in conjunction with a normal- (0.3%) or high-salt (8.0%) diet. Two weeks later, the azilsartan group showed significantly lower blood pressure during the light period than the candesartan and vehicle groups (azilsartan: 103.1 ± 1.0; candesartan: 111.7 ± 2.7; vehicle: 125.5 ± 2.5 mmHg; P < 0.05; azilsartan or candesartan vs. vehicle). The azilsartan group also showed higher urinary fractional excretion of sodium during the dark period than the candesartan and vehicle groups (azilsartan: 21.37 ± 3.69%; candesartan: 14.17 ± 1.42%; vehicle: 13.85 ± 5.30%; P < 0.05 azilsartan vs. candesartan or vehicle). A pressure-natriuresis curve demonstrated that azilsartan treatment restored salt sensitivity. Immunofluorescence and western blotting showed lower levels of Na+-H+ exchanger-3 (NHE3) protein (the major sodium transporter in renal proximal tubules) in the azilsartan group, but not in the candesartan or vehicle groups. However, azilsartan did not affect NHE3 transcription levels. Interestingly, we did not observe increased expression of downstream sodium transporters, which would have compensated for the increased flow of sodium and water due to non-absorption by NHE3. We also confirmed the mechanism stated above using cultured opossum kidney proximal tubular cells. Results revealed that a proteasomal inhibitor (but not a lysosomal inhibitor) blocked the azilsartan-induced decrease in NHE3 protein expression, suggesting that azilsartan increases NHE3 ubiquitination. In

  20. Azilsartan Improves Salt Sensitivity by Modulating the Proximal Tubular Na+-H+ Exchanger-3 in Mice

    PubMed Central

    Hatanaka, Masaki; Kaimori, Jun-Ya; Yamamoto, Satoko; Matsui, Isao; Hamano, Takayuki; Takabatake, Yoshitsugu; Ecelbarger, Carolyn M.; Takahara, Shiro; Isaka, Yoshitaka; Rakugi, Hiromi

    2016-01-01

    A potent angiotensin II type-1 receptor blocker, azilsartan, has been reported to reduce blood pressure more effectively than candesartan. Interestingly, azilsartan can also restore the circadian rhythm of blood pressure. We hypothesized that azilsartan could also improve salt sensitivity; thus, we examined the effect of azilsartan on sodium handling in renal tubules. Subtotal nephrectomized C57BL/6 mice received azilsartan (1.0 mg/kg/day), candesartan (0.3 mg/kg/day), or vehicle via the oral route in conjunction with a normal- (0.3%) or high-salt (8.0%) diet. Two weeks later, the azilsartan group showed significantly lower blood pressure during the light period than the candesartan and vehicle groups (azilsartan: 103.1 ± 1.0; candesartan: 111.7 ± 2.7; vehicle: 125.5 ± 2.5 mmHg; P < 0.05; azilsartan or candesartan vs. vehicle). The azilsartan group also showed higher urinary fractional excretion of sodium during the dark period than the candesartan and vehicle groups (azilsartan: 21.37 ± 3.69%; candesartan: 14.17 ± 1.42%; vehicle: 13.85 ± 5.30%; P < 0.05 azilsartan vs. candesartan or vehicle). A pressure—natriuresis curve demonstrated that azilsartan treatment restored salt sensitivity. Immunofluorescence and western blotting showed lower levels of Na+-H+ exchanger-3 (NHE3) protein (the major sodium transporter in renal proximal tubules) in the azilsartan group, but not in the candesartan or vehicle groups. However, azilsartan did not affect NHE3 transcription levels. Interestingly, we did not observe increased expression of downstream sodium transporters, which would have compensated for the increased flow of sodium and water due to non-absorption by NHE3. We also confirmed the mechanism stated above using cultured opossum kidney proximal tubular cells. Results revealed that a proteasomal inhibitor (but not a lysosomal inhibitor) blocked the azilsartan-induced decrease in NHE3 protein expression, suggesting that azilsartan increases NHE3 ubiquitination. In

  1. The administration of hydrogen sulphide prior to ischemic reperfusion has neuroprotective effects in an acute stroke model

    PubMed Central

    Kim, Kyung-Won; Kim, Jeong-Kon; Jeon, Sang-Beom; Jung, Seung-Chae; Choi, Choong-Gon; Kim, Sang-Tae; Kim, Jinil; Ham, Su Jeong; Shim, Woo-Hyun; Sung, Yu Sub; Ha, Hyun Kwon; Choi, Yoonseok

    2017-01-01

    Emerging evidence has suggested that hydrogen sulfide (H2S) may alleviate the cellular damage associated with cerebral ischemia/reperfusion (I/R) injury. In this study, we assessed using 1H-magnetic resonance imaging/magnetic resonance spectroscopy (1H-MRI/MRS) and histologic analysis whether H2S administration prior to reperfusion has neuroprotective effects. We also evaluated for differences in the effects of H2S treatment at 2 time points. 1H-MRI/MRS data were obtained at baseline, and at 3, 9, and 24 h after ischemia from 4 groups: sham, control (I/R injury), sodium hydrosulfide (NaHS)-30 and NaHS-1 (NaHS delivery at 30 and 1 min before reperfusion, respectively). The total infarct volume and the midline shift at 24 h post-ischemia were lowest in the NaHS-1, followed by the NaHS-30 and control groups. Peri-infarct volume was significantly lower in the NaHS-1 compared to NaHS-30 and control animals. The relative apparent diffusion coefficient (ADC) in the peri-infarct region showed that the NaHS-1 group had significantly lower values compared to the NaHS-30 and control animals and that NaHS-1 rats showed significantly higher relative T2 values in the peri-infarct region compared to the controls. The relative ADC value, relative T2 value, levels of N-acetyl-L-aspartate (NAA), and the NAA, glutamate, and taurine combination score (NGT) in the ischemic core region at 24 h post-ischemia did not differ significantly between the 2 NaHS groups and the control except that the NAA and NGT values were higher in the peri-infarct region of the NaHS-1 animals at 9 h post-ischemia. In the ischemic core and peri-infarct regions, the apoptosis rate was lowest in the NaHS-1 group, followed by the NaHS-30 and control groups. Our results suggest that H2S treatment has neuroprotective effects on the peri-infarct region during the evolution of I/R injury. Furthermore, our findings indicate that the administration of H2S immediately prior to reperfusion produces the highest

  2. A new global analytical potential energy surface of NaH2+ system and dynamical calculation for H(2S) + NaH+(X2Σ+) → Na+(1S) + H2(X1Σg+) reaction

    NASA Astrophysics Data System (ADS)

    Yuan, Meiling; Li, Wentao; Yuan, Jiuchuang

    2018-05-01

    A new global potential energy surface (PES) of the NaH2+ system is constructed by fitting 27,621 ab initio energy points with the neural network method. The root mean square error of the new PES is only 4.1609 × 10-4 eV. Based on the new PES, dynamical calculations have been performed using the time-dependent quantum wave packet method. These results are then compared with the H(2S) + LiH+(X2Σ+) → Li+(1S) + H2(X1Σg+) reaction. The direct abstract mechanism is found to play an important role in the reaction because only forward scattering signals on the differential cross section results for all calculated collision energies.

  3. Protective effect of HOE642, a selective blocker of Na+-H+ exchange, against the development of rigor contracture in rat ventricular myocytes.

    PubMed

    Ruiz-Meana, M; Garcia-Dorado, D; Juliá, M; Inserte, J; Siegmund, B; Ladilov, Y; Piper, M; Tritto, F P; González, M A; Soler-Soler, J

    2000-01-01

    The objective of this study was to investigate the effect of Na+-H+ exchange (NHE) and HCO3--Na+ symport inhibition on the development of rigor contracture. Freshly isolated adult rat cardiomyocytes were subjected to 60 min metabolic inhibition (MI) and 5 min re-energization (Rx). The effects of perfusion of HCO3- or HCO3--free buffer with or without the NHE inhibitor HOE642 (7 microM) were investigated during MI and Rx. In HCO3--free conditions, HOE642 reduced the percentage of cells developing rigor during MI from 79 +/- 1% to 40 +/- 4% (P < 0.001) without modifying the time at which rigor appeared. This resulted in a 30% reduction of hypercontracture during Rx (P < 0.01). The presence of HCO3- abolished the protective effect of HOE642 against rigor. Cells that had developed rigor underwent hypercontracture during Rx independently of treatment allocation. Ratiofluorescence measurement demonstrated that the rise in cytosolic Ca2+ (fura-2) occurred only after the onset of rigor, and was not influenced by HOE642. NHE inhibition did not modify Na+ rise (SBFI) during MI, but exaggerated the initial fall of intracellular pH (BCEFC). In conclusion, HOE642 has a protective effect against rigor during energy deprivation, but only when HCO3--dependent transporters are inhibited. This effect is independent of changes in cytosolic Na+ or Ca2+ concentrations.

  4. Endogenous flow-induced nitric oxide reduces superoxide-stimulated Na/H exchange activity via PKG in thick ascending limbs

    PubMed Central

    Garvin, Jeffrey L.

    2014-01-01

    Luminal flow stimulates endogenous nitric oxide (NO) and superoxide (O2−) production by renal thick ascending limbs (TALs). The delicate balance between these two factors regulates Na transport in TALs; NO enhances natriuresis, whereas O2− augments Na absorption. Endogenous, flow-stimulated O2− enhances Na/H exchange (NHE). Flow-stimulated NO reduces flow-induced O2−, a process mediated by cGMP-dependent protein kinase (PKG). However, whether flow-stimulated, endogenously-produced NO diminishes O2−-stimulated NHE activity and the signaling pathway involved are unknown. We hypothesized that flow-induced NO reduces the stimulation of NHE activity caused by flow-induced O2− via PKG in TALs. Intracellular pH recovery after an acid load was measured as an indicator of NHE activity in isolated, perfused rat TALs. l-Arginine, the NO synthase substrate, decreased NHE activity by 34 ± 5% (n = 5; P < 0.04). The O2− scavenger tempol decreased NHE activity by 46 ± 8% (n = 6; P < 0.004) in the absence of NO. In the presence of l-arginine, the inhibitory effect of tempol on NHE activity was reduced to −19 ± 6% (n = 6; P < 0.03). The soluble guanylate cyclase inhibitor LY-83583 blocked the effect of l-arginine thus restoring tempol's effect on NHE activity to −42 ± 4% (n = 6; P < 0.0005). The PKG inhibitor KT-5823 also inhibited l-arginine's effect on tempol-reduced NHE activity (−43 ± 5%; n = 5; P < 0.03). We conclude that flow-induced NO reduces the stimulatory effect of endogenous, flow-induced O2− on NHE activity in TALs via an increase in cGMP and PKG activation. PMID:25503735

  5. Differences in the effects of Na+-H+ exchange inhibitors on cardiac function and apoptosis in guinea-pig ischemia-reperfused hearts.

    PubMed

    Hotta, Yoshihiro; Nishimaki, Haruaki; Takeo, Tomohiro; Itoh, Gen; Yajima, Michio; Otsuka-Murakami, Hidetsugu; Ishikawa, Naohisa; Kawai, Norio; Huang, Lei; Yamada, Kazuto; Yamamoto, Setsuko; Matsui, Kazuki; Ohashi, Naohito

    2004-10-25

    The protective effects of the Na+-H+ exchange (NHE) inhibitors SM-198110 (2-[[(aminoiminomethyl) amino] carbonyl]-4-chloro-1H-indole-1-propanesulfonic acid monohydrate) and SM-197378 (N-(aminoiminomethyl)-1-methyl-7-(sulfooxy)-4-(trifluoromethyl)-1H-indole-2-carboxamide monohydrate) were investigated in perfused Langendorff guinea-pig hearts subjected to ischemia (40 min) and reperfusion (40 min). The recovery of left ventricular developed pressure (LVDP) from ischemia by reperfusion was 39.0% in the control, while in the hearts pretreated with SM-198110 or SM-197378 (10(-7) M), it was about 100%. The ATP level, monitored simultaneously by (31)P-nuclear magnetic resonance spectrometry, was already higher than the control value at the end of the ischemic period, and the elevation in Na+ or Ca2+ fluorometric signals induced during ischemia was suppressed. In post-treated hearts, the LVDP recovery rate was significantly higher with SM-198110 than with SM-197378. By in vitro electron paramagnetic resonance spectrometry, SM-197378 was found to directly quench the active oxygen radical, whereas SM-198110 had no effect. Numbers of apoptotic cardiomyocytes after ischemia (1 h) followed by reperfusion (5 h) were significantly lower in SM-197378-treated than in SM-198110-treated hearts, consistent with the level of activity of caspase-3. These results suggest that the antioxidant effects of NHE inhibitors have an important role in apoptosis during ischemia-reperfusion, but apoptosis is not a major manifestation of cardiac function during postischemic recovery, and that NHE-sensitive mechanisms of reperfusion injury promote both necrotic and apoptotic processes death.

  6. Enhanced salt resistance in apple plants overexpressing a Malus vacuolar Na+/H+ antiporter gene is associated with differences in stomatal behavior and photosynthesis.

    PubMed

    Li, Chao; Wei, Zhiwei; Liang, Dong; Zhou, Shasha; Li, Yonghong; Liu, Changhai; Ma, Fengwang

    2013-09-01

    High salinity is a major abiotic factor that limits crop production. The dwarfing apple rootstock M.26 is sensitive to such stress. To obtain an apple that is adaptable to saline soils, we transformed this rootstock with a vacuolar Na(+)/H(+) antiporter, MdNHX1. Differences in salt tolerance between transgenic and wild-type (WT) rootstocks were examined under field conditions. We also compared differences when 'Naganofuji No. 2' apple was grafted onto these transgenic or WT rootstocks. Plants on the transgenic rootstocks grew well during 60 d of mild stress (100 mM NaCl) while the WT exhibited chlorosis, inhibited growth and even death. Compared with the untreated control, the stomatal density was greater in both non-grafted and grafted WT plants exposed to 200 mM NaCl. In contrast, that density was significantly decreased in leaves from grafted transgenic plants. At 200 mM NaCl, net photosynthesis, stomatal conductance, intercellular CO2 concentration, and chlorophyll contents were markedly reduced in the WT, whereas the declines in those values were only minor in similarly stressed transgenic plants. Therefore, we conclude that overexpressing plants utilize a better protective mechanism for retaining higher photosynthetic capacity. Furthermore, this contrast in tolerance and adaptability to stress is linked to differences in stomatal behavior and photosynthetic rates. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  7. Vasoconstriction triggered by hydrogen sulfide: Evidence for Na+,K+,2Cl-cotransport and L-type Ca2+ channel-mediated pathway.

    PubMed

    Orlov, Sergei N; Gusakova, Svetlana V; Smaglii, Liudmila V; Koltsova, Svetlana V; Sidorenko, Svetalana V

    2017-12-01

    This study examined the dose-dependent actions of hydrogen sulfide donor sodium hydrosulphide (NaHS) on isometric contractions and ion transport in rat aorta smooth muscle cells (SMC). Isometric contraction was measured in ring aortas segments from male Wistar rats. Activity of Na + /K + -pump and Na + ,K + ,2Cl - cotransport was measured in cultured endothelial and smooth muscle cells from the rat aorta as ouabain-sensitive and ouabain-resistant, bumetanide-sensitive components of the 86 Rb influx, respectively. NaHS exhibited the bimodal action on contractions triggered by modest depolarization ([K + ] o =30 mM). At 10 -4 M, NaHS augmented contractions of intact and endothelium-denuded strips by ~ 15% and 25%, respectively, whereas at concentration of 10 -3  M it decreased contractile responses by more than two-fold. Contractions evoked by 10 -4  M NaHS were completely abolished by bumetanide, a potent inhibitor of Na + ,K + ,2Cl - cotransport, whereas the inhibition seen at 10 -3  M NaHS was suppressed in the presence of K + channel blocker TEA. In cultured SMC, 5×10 -5  M NaHS increased Na + ,K + ,2Cl - - cotransport without any effect on the activity of this carrier in endothelial cells. In depolarized SMC, 45 Ca influx was enhanced in the presence of 10 -4  M NaHS and suppressed under elevation of [NaHS] up to 10 -3  M. 45 Ca influx triggered by 10 -4  M NaHS was abolished by bumetanide and L-type Ca 2+ channel blocker nicardipine. Our results strongly suggest that contractions of rat aortic rings triggered by low doses of NaHS are mediated by activation of Na + ,K + ,2Cl - cotransport and Ca 2+ influx via L-type channels.

  8. Proline residues in transmembrane segment IV are critical for activity, expression and targeting of the Na+/H+ exchanger isoform 1.

    PubMed Central

    Slepkov, Emily R; Chow, Signy; Lemieux, M Joanne; Fliegel, Larry

    2004-01-01

    NHE1 (Na+/H+ exchanger isoform 1) is a ubiquitously expressed integral membrane protein that regulates intracellular pH in mammalian cells. Proline residues within transmembrane segments have unusual properties, acting as helix breakers and increasing flexibility of membrane segments, since they lack an amide hydrogen. We examined the importance of three conserved proline residues in TM IV (transmembrane segment IV) of NHE1. Pro167 and Pro168 were mutated to Gly, Ala or Cys, and Pro178 was mutated to Ala. Pro168 and Pro178 mutant proteins were expressed at levels similar to wild-type NHE1 and were targeted to the plasma membrane. However, the mutants P167G (Pro167-->Gly), P167A and P167C were expressed at lower levels compared with wild-type NHE1, and a significant portion of P167G and P167C were retained intracellularly, possibly indicating induced changes in the structure of TM IV. P167G, P167C, P168A and P168C mutations abolished NHE activity, and P167A and P168G mutations caused markedly decreased activity. In contrast, the activity of the P178A mutant was not significantly different from that of wild-type NHE1. The results indicate that both Pro167 and Pro168 in TM IV of NHE1 are required for normal NHE activity. In addition, mutation of Pro167 affects the expression and membrane targeting of the exchanger. Thus both Pro167 and Pro168 are strictly required for NHE function and may play critical roles in the structure of TM IV of the NHE. PMID:14680478

  9. Clinical and Experimental Evidences of Hydrogen Sulfide Involvement in Lead-Induced Hypertension

    PubMed Central

    Possomato-Vieira, José Sérgio; do Nascimento, Regina Aparecida; Wandekin, Rodrigo Roldão; Caldeira-Dias, Mayara; Chimini, Jessica Sabbatine; da Silva, Maria Luiza Santos

    2018-01-01

    Lead- (Pb-) induced hypertension has been shown in humans and experimental animals and cardiovascular effects of hydrogen sulfide (H2S) have been reported previously. However, no studies examined involvement of H2S in Pb-induced hypertension. We found increases in diastolic blood pressure and mean blood pressure in Pb-intoxicated humans followed by diminished H2S plasmatic levels. In order to expand our findings, male Wistar rats were divided into four groups: Saline, Pb, NaHS, and Pb + NaHS. Pb-intoxicated animals received intraperitoneally (i.p.) 1st dose of 8 μg/100 g of Pb acetate and subsequent doses of 0.1 μg/100 g for seven days and sodium hydrosulfide- (NaHS-) treated animals received i.p. NaHS injections (50 μmol/kg/twice daily) for seven days. NaHS treatment blunted increases in systolic blood pressure, increased H2S plasmatic levels, and diminished whole-blood lead levels. Treatment with NaHS in Pb-induced hypertension seems to induce a protective role in rat aorta which is dependent on endothelium and seems to promote non-NO-mediated relaxation. Pb-intoxication increased oxidative stress in rats, while treatment with NaHS blunted increases in plasmatic MDA levels and increased antioxidant status of plasma. Therefore, H2S pathway may be involved in Pb-induced hypertension and treatment with NaHS exerts antihypertensive effect, promotes non-NO-mediated relaxation, and decreases oxidative stress in rats with Pb-induced hypertension. PMID:29789795

  10. Does menopause influence nocturnal awakening with headache?

    PubMed

    Lucchesi, L M; Hachul, H; Yagihara, F; Santos-Silva, R; Tufik, S; Bittencourt, L

    2013-06-01

    The aim of the present study was to assess whether menopausal status influences the occurrence of nocturnal awakening with headache (NAH) in the female population of Sao Paulo, Brazil. We also examined the relationship of this complaint to sociodemographic determinants, hot flushes, sleep quality and parameters, anxiety and depressive symptoms, somnolence and fatigue according to menopausal status. The female population of the Sao Paulo Epidemiologic Sleep Study (EPISONO) (n = 576) was divided according to menopausal status (pre-, peri-, early and late menopause) based on questionnaires and hormonal blood measures. The complaint of waking up because of a headache at least once a week was assessed by the UNIFESP Sleep questionnaire. Additionally, hot flushes, sleep complaints, anxiety and depressive symptoms, somnolence and fatigue were assessed by specific questionnaires. A full-night polysomnography assessed sleep parameters. The prevalence of NAH in women in the Sao Paulo population was 13.3%. Perimenopause was associated with a higher risk of having NAH (odds ratio 13.9; 95% confidence interval 4.3-45.2). More complaints of NAH were observed in obese women. All the groups with NAH showed more hot flushes, worse subjective sleep quality, more complaints of insomnia, anxiety symptoms and fatigue. We observed a constellation of symptoms in women according to menopausal status and NAH that included hot flushes, sleep complaints, more anxiety symptoms and fatigue. Moreover, some of these symptoms were more frequent in perimenopausal women with NAH. Therefore, we concluded that menopausal status influences NAH and the women in perimenopause presented a high risk of having this complaint.

  11. Role of Na+ conductance, Na+-H+ exchange, and Na+-K+-2Cl− symport in the regulatory volume increase of rat hepatocytes

    PubMed Central

    Wehner, Frank; Tinel, Hanna

    1998-01-01

    In rat hepatocytes under hypertonic stress, the entry of Na+ (which is thereafter exchanged for K+ via Na+-K+-ATPase) plays the key role in regulatory volume increase (RVI).In the present study, the contributions of Na+ conductance, Na+-H+ exchange and Na+-K+-2Cl− symport to this process were quantified in confluent primary cultures by means of intracellular microelectrodes and cable analysis, microfluorometric determinations of cell pH and buffer capacity, and measurements of frusemide (furosemide)/bumetanide-sensitive 86Rb+ uptake, respectively. Osmolarity was increased from 300 to 400 mosmol l−1 by addition of sucrose.The experiments indicate a relative contribution of approximately 4:1:1 to hypertonicity-induced Na+ entry for the above-mentioned transporters and the overall Na+ yield equalled 51 mmol l−1 (10 min)−1.This Na+ gain is in good agreement with the stimulation of Na+ extrusion via Na+-K+-ATPase plus the actual increase in cell Na+, namely 55 mmol l−1 (10 min)−1, as was determined on the basis of ouabain-sensitive 86Rb+ uptake and by means of Na+-sensitive microelectrodes, respectively.The overall increase in Na+ and K+ activity plus the expected concomitant increase in cell Cl− equalled 68 mmol l−1, which fits well with the increase in osmotic activity expected to occur from an initial cell shrinkage to 87.5 % and a RVI to 92.6 % of control, namely 53 mosmol l−1.The prominent role of Na+ conductance in the RVI of rat hepatocytes could be confirmed on the basis of the pharmacological profile of this process, which was characterized by means of confocal laser-scanning microscopy. PMID:9481677

  12. Expression of a novel isoform of Na+/H+ exchanger 3 in the kidney and intestine of banded houndshark, Triakis scyllium

    PubMed Central

    Li, Shanshan; Takabe, Souichirou; Chen, An-Ping; Romero, Michael F.; Umezawa, Takahiro; Nakada, Tsutomu; Hyodo, Susumu; Hirose, Shigehisa

    2013-01-01

    Na+/H+ exchanger 3 (NHE3) provides one of the major Na+ absorptive pathways of the intestine and kidney in mammals, and recent studies of aquatic vertebrates (teleosts and elasmobranchs) have demonstrated that NHE3 is expressed in the gill and plays important roles in ion and acid-base regulation. To understand the role of NHE3 in elasmobranch osmoregulatory organs, we analyzed renal and intestinal expressions and localizations of NHE3 in a marine elasmobranch, Japanese banded houndshark (Triakis scyllium). mRNA for Triakis NHE3 was most highly expressed in the gill, kidney, spiral intestine, and rectum. The kidney and intestine expressed a transcriptional isoform of NHE3 (NHE3k/i), which has a different amino terminus compared with that of NHE3 isolated from the gill (NHE3g), suggesting that NHE3k/i and NHE3g arise from a single gene by alternative promoter usage. Immunohistochemical analyses of the Triakis kidney demonstrated that NHE3k/i is expressed in the apical membrane of a part of the proximal and late distal tubules in the sinus zone. In the bundle zone of the kidney, NHE3k/i was expressed in the apical membrane of the early distal tubules known as the diluting segment. In the spiral intestine and rectum, NHE3k/i was localized toward the apical membrane of the epithelial cells. The transcriptional levels of NHE3k/i were increased in the kidney when Triakis was acclimated in 130% seawater, whereas those in the spiral intestine were increased in fish acclimated in diluted seawater. These results suggest that NHE3 is involved in renal Na+ reabsorption, urine acidification, and intestinal Na+ absorption in elasmobranchs. PMID:23485868

  13. Intracellular pH regulatory mechanism in human atrial myocardium: functional evidence for Na(+)/H(+) exchanger and Na(+)/HCO(3)(-) symporter.

    PubMed

    Loh, Shih-Hurng; Chen, Wei-Hwa; Chiang, Cheng-Hsien; Tsai, Chien-Sung; Lee, Guo-Chen; Jin, Jong-Shiaw; Cheng, Tzu-Hurng; Chen, Jin-Jer

    2002-01-01

    Intracellular pH (pH(i)) exerts considerable influence on cardiac contractility and rhythm. Over the last few years, extensive progress has been made in understanding the system that controls pH(i) in animal cardiomyocytes. In addition to the housekeeping Na(+)-H(+) exchanger (NHE), the Na(+)-HCO(3)(-) symporter (NHS) has been demonstrated in animal cardiomyocytes as another acid extruder. However, whether the NHE and NHS functions exist in human atrial cardiomyocytes remains unclear. We therefore investigated the mechanism of pH(i) recovery from intracellular acidosis (induced by NH(4)Cl prepulse) using intracellular 2',7'-bis(2-carboxethyl)-5(6)-carboxy-fluorescein fluorescence in human atrial myocardium. In HEPES (nominally HCO(3)(-)-free) Tyrode solution, pH(i) recovery from induced intracellular acidosis could be blocked completely by 30 microM 3-methylsulfonyl-4-piperidinobenzoyl, guanidine hydrochloride (HOE 694), a specific NHE inhibitor, or by removing extracellular Na(+). In 3% CO(2)-HCO(3)(-) Tyrode solution, HOE 694 only slowed the pH(i) recovery, while addition of HOE 694 together with 4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid (an NHS inhibitor) or removal of extracellular Na(+) inhibited the acid extrusion entirely. Therefore, in the present study, we provided evidence that two acid extruders involved in acid extrusion in human atrial myocytes, one which is HCO(3)(-) independent and one which is HCO(3)(-) dependent, are mostly likely NHE and NHS, respectively. When we checked the percentage of contribution of these two carriers to pH(i) recovery following induced acidosis, we found that the activity of NHE increased steeply in the acid direction, while that of NHS did not change. Our present data indicate for the first time that two acid extruders, NHE and NHS, exist functionally and pH(i) dependently in human atrial cardiomyocytes. Copyright 2002 National Science Council, ROC and S. Karger AG, Basel

  14. Distinct mechanisms underlie adaptation of proximal tubule Na+/H+ exchanger isoform 3 in response to chronic metabolic and respiratory acidosis.

    PubMed

    Silva, Pedro Henrique Imenez; Girardi, Adriana Castello Costa; Neri, Elida Adalgisa; Rebouças, Nancy Amaral

    2012-04-01

    The Na(+/)H(+) exchanger isoform 3 (NHE3) is essential for HCO(3)(-) reabsorption in renal proximal tubules. The expression and function of NHE3 must adapt to acid-base conditions. The goal of this study was to elucidate the mechanisms responsible for higher proton secretion in proximal tubules during acidosis and to evaluate whether there are differences between metabolic and respiratory acidosis with regard to NHE3 modulation and, if so, to identify the relevant parameters that may trigger these distinct adaptive responses. We achieved metabolic acidosis by lowering HCO(3)(-) concentration in the cell culture medium and respiratory acidosis by increasing CO(2) tension in the incubator chamber. We found that cell-surface NHE3 expression was increased in response to both forms of acidosis. Mild (pH 7.21 ± 0.02) and severe (6.95 ± 0.07) metabolic acidosis increased mRNA levels, at least in part due to up-regulation of transcription, whilst mild (7.11 ± 0.03) and severe (6.86 ± 0.01) respiratory acidosis did not up-regulate NHE3 expression. Analyses of the Nhe3 promoter region suggested that the regulatory elements sensitive to metabolic acidosis are located between -466 and -153 bp, where two consensus binding sites for SP1, a transcription factor up-regulated in metabolic acidosis, were localised. We conclude that metabolic acidosis induces Nhe3 promoter activation, which results in higher mRNA and total protein level. At the plasma membrane surface, NHE3 expression was increased in metabolic and respiratory acidosis alike, suggesting that low pH is responsible for NHE3 displacement to the cell surface.

  15. Artificial Turbulence for Imaging and Wave Propagation. Volume 3432

    DTIC Science & Technology

    1998-07-01

    zunehmenden Maße Möglichkeiten gesucht, lokale Unscharfen in dem Objektbild eines Fernrohres oder einer Kamera , welche beispielsweise durch...Verwendung von Kameras oder Fernrohren zur Beobachtung von Objekten innerhalb der Erdatmosphäre oder durch diese hindurch treten lokale Unscharfen in dem...Trägerschicht aufgebracht sind. Die Einrichtung wird in den Strahlengang des betreffenden Beobachtungsgerätes, beispielsweise einer Kamera oder eines

  16. Neuroprotective effects of sodium hydrosulfide against β-amyloid-induced neurotoxicity

    PubMed Central

    Li, Xiao-Hui; Deng, Yuan-Yuan; Li, Fei; Shi, Jing-Shan; Gong, Qi-Hai

    2016-01-01

    Alzheimer's disease (AD) is known to be caused by the accumulation of amyloid-β peptide (Aβ). The accumulation of Aβ has been shown to cause learning and memory impairment in rats, and it has been shown that hydrogen sulfide donors, such as sodium hydrosulfide (NaHS) can attenuate these effects. However, the underlying mechanisms have not yet been fully eludicated. This study was designed to investigate whether NaHS attenuates the inflammation and apoptosis induced by Aβ. We demonstrated that NaHS attenuated Aβ25–35-induced neuronal reduction and apoptosis, and inhibited the activation of pro-caspase-3. It also decreased the protein expresion of phosphodiesterase 5 (PDE5) in the hippocampus of the rats. In addition, NaHS upregulated the expression of peroxisome proliferator-activated receptor (PPAR)-α and PPAR-γ, but it did not affect the expression of PPAR-β. Moreover, the Aβ25–35-exposed rats exhibited a decrease in IκB-α degradation and an increase in nuclear factor-κB (NF-κB) p65 phosphorylation levels, whereas these effects were attenuated by NaHS. Our data suggest that NaHS prevents Aβ-induced neurotoxicity via the upregulation of PPAR-α and PPAR-γ and the inhibition of PDE5. Hence NaHS may prove to be beneficial in the treatment of AD. PMID:27511125

  17. Enteral administration of monosodium phosphate, monopotassium phosphate and monocalcium phosphate for the treatment of hypophosphataemia in lactating dairy cattle.

    PubMed

    Idink, M J; Grünberg, W

    2015-05-09

    Hypohosphataemia is a frequent finding in early lactating and anorectic dairy cows. Sodium phosphate is commonly used for oral phosphorus (P) supplementation, although other phosphate salts may present useful treatment alternatives. Objectives of this study were to compare the efficacy of monopotassium phosphate (KH2PO4) and monocalcium phosphate (Ca(H2PO4)2) to monosodium phosphate (NaH2PO4) in P-depleted cows. Furthermore, the effect of concentrated NaH2PO4 on the reticular groove reflex was studied. Six healthy but P-depleted dairy cows underwent four treatments in randomised order. Treatments consisted of intraruminal administration of NaH2PO4, KH2PO4 and Ca(H2PO4)2 providing the equivalent of 60 g P. A fourth treatment consisting of concentrated NaH2PO4 combined with acetaminophen as a marker substance was administered orally to determine whether the reticular groove reflex could be induced. Intraruminal administration of NaH2PO4 and KH2PO4 resulted in similar increases in plasma Pi concentrations ([Pi]) while intraruminal Ca(H2PO4)2 resulted in lower increases in plasma [Pi]. Oral and intraruminal administration of NaH2PO4 resulted in similar times to peak plasma [Pi] and acetaminophen concentration, indicating that concentrated NaH2PO4 administered orally did not trigger the reticular groove reflex. These results suggest that oral administration of KH2PO4 is equally effective as NaH2PO4. Oral administration of Ca(H2PO4)2 in contrast has a less pronounced effect on the plasma [Pi]. British Veterinary Association.

  18. A universal mechanism for transport and regulation of CPA sodium proton exchangers.

    PubMed

    Călinescu, Octavian; Fendler, Klaus

    2015-09-01

    Recent studies performed on a series of Na+/H+ exchangers have led us to postulate a general mechanism for Na+/H+ exchange in the monovalent cation/proton antiporter superfamily. This simple mechanism employs a single binding site for which both substrates compete. The developed kinetic model is self-regulatory, ensuring down-regulation of transport activity at extreme pH, and elegantly explains the pH-dependent activity of Na+/H+ exchangers. The mechanism was experimentally verified and shown to describe both electrogenic and electroneutral exchangers. Using a small number of parameters, exchanger activity can be modeled under different conditions, providing insights into the physiological role of Na+/H+ exchangers.

  19. National AIDS Hotline: HIV and AIDS information service through a toll-free telephone system.

    PubMed Central

    Waller, R R; Lisella, L W

    1991-01-01

    The National AIDS Hotline (NAH), a service of the Centers for Disease Control (CDC), is an information resource for the population of the United States, its Territories, and Puerto Rico concerning the human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS). Since its inception in 1983, NAH has grown to be the world's largest health-related hotline service. NAH has received an average of more than 1.4 million calls per year since October 1987. Services of NAH include responding to the public's questions about HIV and AIDS and providing referrals to State and local resources. All services, including HIV and AIDS publications, are provided free of charge. The public contacts NAH 24 hours a day, 7 days a week, through a toll-free telephone system. Services are available to English-speaking, Spanish-speaking, and deaf populations. Each service has its own telephone number--English-speaking, 1-800-342-2437; Spanish-speaking, 1-800-344-7432; TTY service for the deaf, 1-800-243-7889. NAH employs approximately 170 information specialists to answer calls. The facility uses modern telecommunications technology to effectively manage and direct calls to 43 work stations. Each work station is supported by a personal computer that allows access to CDC's National AIDS Clearinghouse data bases for referrals and publication ordering. NAH ensures that information provided to the public is current, accurate, and consistent with approved government policy. Quality assurance reviews address call management, delivery of information, and content of calls. PMID:1659708

  20. Hydrogen sulfide upregulates heme oxygenase-1 expression in rats with volume overload-induced heart failure

    PubMed Central

    ZHANG, CHAO-YING; LI, XIAO-HUI; ZHANG, TING; FU, JIN; CUI, XIAO-DAI

    2013-01-01

    The present study investigated the role of hydrogen sulfide (H2S), a novel gaseous transmitter, in chronic heart failure (CHF) induced by left-to-right shunt, leading to volume overload. Thirty male Sprague-Dawley rats were randomly divided into four groups: the shunt group, the sham group, the shunt + sodium hydrosulfide (NaHS) group and the sham + NaHS group. CHF was induced in the rats by abdominal aorta-inferior vena cava shunt operation. Rats in the shunt + NaHS and sham + NaHS groups were injected intraperitoneally with NaHS (H2S donor). Haemodynamic parameters were measured 8 weeks after surgery. In addition, left ventricular heme oxygenase (HO)-1 mRNA expression was measured by real-time PCR. Protein expression of HO-1 was evaluated by western blot analysis. Eight weeks after surgery, compared to the sham group, the left ventricular systolic pressure (LVSP) and left ventricular peak rate of contraction and relaxation (LV±dp/dtmax) were significantly reduced; the left ventricular end-diastolic pressure (LVEDP) was significantly increased in the shunt group (all P<0.05). However, NaHS increased LVSP and LV±dp/dtmax (all P<0.05) and decreased LVEDP (P<0.05). Protein expression of HO-1 was significantly decreased in the shunt group compared to that in the sham group (P<0.05). NaHS increased protein expression of HO-1 compared to that in the shunt group (P<0.05). HO-1 mRNA expression was significantly increased in the shunt + NaHS group compared to that in the shunt group (P<0.01). The present study demonstrated that H2S may play a protective role in volume overload-induced CHF by upregulating protein and mRNA expression of HO-1. PMID:24648967

  1. Effects of hydrogen sulfide on inflammation in caerulein-induced acute pancreatitis

    PubMed Central

    2009-01-01

    Background Hydrogen sulfide (H2S), a gaseous mediator plays an important role in a wide range of physiological and pathological processes. H2S has been extensively studied for its various roles in cardiovascular and neurological disorders. However, the role of H2S in inflammation is still controversial. The current study was aimed to investigate the therapeutic potential of sodium hydrosulfide (NaHS), an H2S donor in in vivo model of acute pancreatitis in mice. Methods Acute pancreatitis was induced in mice by hourly caerulein injections (50 μg/kg) for 10 hours. Mice were treated with different dosages of NaHS (5 mg/kg, 10 mg/kg or 15 mg/kg) or with vehicle, distilled water (DW). NaHS or DW was administered 1 h before induction of pancreatitis. Mice were sacrificed 1 h after the last caerulein injection. Blood, pancreas and lung tissues were collected and were processed to measure the plasma amylase, myeloperoxidase (MPO) activities in pancreas and lung and chemokines and adhesion molecules in pancreas and lung. Results It was revealed that significant reduction of inflammation, both in pancreas and lung was associated with NaHS 10 mg/kg. Further the anti-inflammatory effects of NaHS 10 mg/kg were associated with reduction of pancreatic and pulmonary inflammatory chemokines and adhesion molecules. NaHS 5 mg/kg did not cause significant improvement on inflammation in pancreas and associated lung injury and NaHS 15 mg/kg did not further enhance the beneficial effects seen with NaHS 10 mg/kg. Conclusion In conclusion, these data provide evidence for anti-inflammatory effects of H2S based on its dosage used. PMID:20040116

  2. The protective effect of hydrogen sulfide (H2S) on traumatic brain injury (TBI) induced memory deficits in rats.

    PubMed

    Karimi, Seyed Asaad; Hosseinmardi, Narges; Janahmadi, Mahyar; Sayyah, Mohammad; Hajisoltani, Razieh

    2017-09-01

    Traumatic brain injury (TBI), as an expanding public health epidemic, is a common cause of death among youth. TBI is associated with cognitive deficits and memory impairment. Hydrogen sulfide (H 2 S), a novel gaseous mediator, has been recognized as an important neuromodulator and neuroprotective agent in the central nervous system. In the present study the potential neuroprotective role of sodium hydrosulfide (NaHS), an H 2 S donor on TBI induced memory deficit in a rat model of controlled cortical impact (CCI) injury was investigated. CCI model was used to induce TBI. Male rats were randomly assigned into the following groups: control, sham, sham treated with NaHS, TBI, and TBI treated with NaHS (3 and 5mg/kg). NaHS was injected intraperitoneally 5min before TBI induction. Learning and memory were assessed using Morris water maze (MWM) on days 8-12 following injury. CCI resulted in MWM deficits. Injured animals showed a slower rate of acquisition with respect to the sham-operated animals [F (1, 24)=13.97, P<0.01, two-way ANOVA]. NaHS improved spatial memory impairment of injured rats. Treatment with NaHS (5 mg/kg) decreased the escape latency [F (1, 24)=7.559, P<0.05, two-way ANOVA] and traveled distance [F (1, 12)=6.398, P<0.05, Two way ANOVA)]. In probe test, injured animals spent less time in target zone (P<0.05, unpaired t-test) and NaHS did not have any effect on this parameter (p>0.05, one way ANOVA). These findings suggest that NaHS has a neuroprotective effect on TBI-induced memory impairment in rats. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Beschallungstechnik, Beschallungsplanung und Simulation

    NASA Astrophysics Data System (ADS)

    Ahnert, Wolfgang; Goertz, Anselm

    Die primäre Aufgabe einer Lautsprecheranlage ist es, Musik, Sprache oder auch Signaltöne und Geräusche wiederzugeben. Diese können von einem Tonträger kommen (CD, Sprachspeicher), von einem anderen Ort übertragen (Zuspielung über Radio, TV, Telefon) oder vor Ort erzeugt werden. Letzteres umfasst Konzerte, Ansprachen, Durchsagen oder künstlerische Darbietungen, bei denen es meist darum geht, eine bereits vorhandene Quelle einer größeren oder weiter verteilten Anzahl von Personen zugänglich zu machen.

  4. Activity and protein expression of the Na+/H+ exchanger is reduced in syncytiotrophoblast microvillous plasma membranes isolated from preterm intrauterine growth restriction pregnancies.

    PubMed

    Johansson, M; Glazier, J D; Sibley, C P; Jansson, T; Powell, T L

    2002-12-01

    Regulation of syncytiotrophoblast intracellular pH is critical to optimum enzymatic and transport functions of the placenta. Previous studies of Na(+)/H(+) exchanger (NHE) activity in the placenta from pregnancies complicated by intrauterine growth restriction (IUGR) have produced conflicting results. The possible role of altered placental pH regulation in the development of acidosis in some fetuses subjected to IUGR remains to be fully established. We investigated the activity and protein expression of the NHE in syncytiotrophoblast microvillous (MVM) plasma membranes isolated from preterm and term placentas obtained from uncomplicated and IUGR pregnancies. Western blotting showed that the expression of NHE isoforms 1, 2, and 3 was approximately 10-fold greater in MVM than in basal plasma membrane (BM). Immunohistochemistry localized NHE-1 and NHE-2 to MVM and BM and NHE-3 to the MVM, BM, and cytoplasm of the syncytiotrophoblast. NHE-1 expression in MVM from preterm IUGR placentas was reduced by 55%, compared with gestational age-matched controls (P < 0.05, n = 6 and n = 16, respectively), whereas NHE-1 expression was unaltered in term IUGR placentas (n = 8). The activity (amiloride-sensitive Na(+) uptake) of NHE in MVM from IUGR preterm placentas was reduced by 48% (P < 0.05, n = 6). In contrast, MVM NHE activity was unchanged in term IUGR (n = 7). Using Northern blotting, no difference could be demonstrated in NHE-1 mRNA expression between IUGR and control groups. The reduced activity and expression of NHE in MVM of preterm IUGR placentas may compromise placental function and may contribute to the development of fetal acidosis in preterm IUGR fetuses.

  5. Inhibition of Na+/H+ exchanger enhances low pH-induced L-selectin shedding and β2-integrin surface expression in human neutrophils

    PubMed Central

    Kaba, Nubia K.; Schultz, Joanne; Law, Foon-Yee; Lefort, Craig T.; Martel-Gallegos, Guadalupe; Kim, Minsoo; Waugh, Richard E.; Arreola, Jorge; Knauf, Philip A.

    2008-01-01

    Ischemia-reperfusion injury is a common pathological occurrence causing tissue damage in heart attack and stroke. Entrapment of neutrophils in the vasculature during ischemic events has been implicated in this process. In this study, we examine the effects that lactacidosis and consequent reductions in intracellular pH (pHi) have on surface expression of adhesion molecules on neutrophils. When human neutrophils were exposed to pH 6 lactate, there was a marked decrease in surface L-selectin (CD62L) levels, and the decrease was significantly enhanced by inclusion of Na+/H+ exchanger (NHE) inhibitor 5-(N,N-hexamethylene)amiloride (HMA). Similar effects were observed when pHi was reduced while maintaining normal extracellular pH, by using an NH4Cl prepulse followed by washes and incubation in pH 7.4 buffer containing NHE inhibitors [HMA, cariporide, or 5-(N,N-dimethyl)amiloride (DMA)]. The amount of L-selectin shedding induced by different concentrations of NH4Cl in the prepulse correlated with the level of intracellular acidification with an apparent pK of 6.3. In contrast, β2-integrin (CD11b and CD18) was only slightly upregulated in the low-pHi condition and was enhanced by NHE inhibition to a much lesser extent. L-selectin shedding was prevented by treating human neutrophils with inhibitors of extracellular metalloproteases (RO-31-9790 and KD-IX-73-4) or with inhibitors of intracellular signaling via p38 MAP kinase (SB-203580 and SB-239063), implying a transmembrane effect of pHi. Taken together, these data suggest that the ability of NHE inhibitors such as HMA to reduce ischemia-reperfusion injury may be related to the nearly complete removal of L-selectin from the neutrophil surface. PMID:18829897

  6. Transplantate und Implantate im Mittelohrbereich - Teil 1 (Stand 2002)

    NASA Astrophysics Data System (ADS)

    Kempf, Hans-Georg; Lenarz, Thomas; Eckert, Karl-Ludwig

    In Deutschland leben ungefähr 12 Millionen Menschen, die an einer ein- oder beidseitigen Schwerhörigkeit leiden. Diese kann angeboren oder im Laufe des Lebens erworben sein. Klinisch und therapeutisch wichtig ist die Unterscheidung, ob die Ursache der Schwerhörigkeit im Bereich des Mittelohres, d. h. der Schallübertragung, oder im Bereich des Innenohres, der Hörnerven und der zentralen Hörbahnabschnitte, d. h. der Schallempfindung, liegt. 2,5 Millionen Schwerhörige haben dabei das Problem der Schallübertragung, d.h. die Störung liegt im Mittelohrbereich, und hier kann man in der Regel mit operativen, mikrochirurgisch durchgeführten Massnahmen helfen [1, 2]. Im Vordergrund steht als Ursache hier die chronische Mittelohrentzündung, die sich als Perforation des Trommelfells, als Defekt oder Unterbrechung der Gehörknöchelchen oder auch als Cholesteatom, einer sogenannte Knocheneiterung äussern kann [3]. Therapeutisch und damit als Prinzip der operativen Hörverbesserung steht primär der Verschluss des Trommelfells oder eine Rekonstruktion der Gehörknöchelchen an.

  7. Distinctly Different Glass Transition Behaviors of Trehalose Mixed with Na2HPO 4 or NaH 2PO 4: Evidence for its Molecular Origin.

    PubMed

    Weng, Lindong; Elliott, Gloria D

    2015-07-01

    The present study is aimed at understanding how the interactions between sugar molecules and phosphate ions affect the glass transition temperature of their mixtures, and the implications for pharmaceutical formulations. The glass transition temperature (Tg) and the α-relaxation temperature (Tα) of dehydrated trehalose/sodium phosphate mixtures (monobasic or dibasic) were determined by differential scanning calorimetry and dynamic mechanical analysis, respectively. Molecular dynamics simulations were also conducted to investigate the microscopic interactions between sugar molecules and phosphate ions. The hydrogen-bonding characteristics and the self-aggregation features of these mixtures were quantified and compared. Thermal analysis measurements demonstrated that the addition of NaH2PO4 decreased both the glass transition temperature and the α-relaxation temperature of the dehydrated trehalose/NaH2PO4 mixture compared to trehalose alone while both Tg and Tα were increased by adding Na2HPO4 to pure trehalose. The hydrogen-bonding interactions between trehalose and HPO4(2-) were found to be stronger than both the trehalose-trehalose hydrogen bonds and those formed between trehalose and H2PO4(-). The HPO4(2-) ions also aggregated into smaller clusters than H2PO4(-) ions. The trehalose/Na2HPO4 mixture yielded a higher T g than pure trehalose because marginally self-aggregated HPO4(2-) ions established a strengthened hydrogen-bonding network with trehalose molecules. In contrast H2PO4(-) ions served only as plasticizers, resulting in a lower Tg of the mixtures than trehalose alone, creating large-sized ionic pockets, weakening interactions, and disrupting the original hydrogen-bonding network amongst trehalose molecules.

  8. Distinctly Different Glass Transition Behaviors of Trehalose Mixed with Na2HPO4 or NaH2PO4: Evidence for its Molecular Origin

    PubMed Central

    Weng, Lindong; Elliott, Gloria D.

    2015-01-01

    Purpose The present study is aimed at understanding how the interactions between sugar molecules and phosphate ions affect the glass transition temperature of their mixtures, and the implications for pharmaceutical formulations. Methods The glass transition temperature (Tg) and the α-relaxation temperature (Tα) of dehydrated trehalose/sodium phosphate mixtures (monobasic or dibasic) were determined by differential scanning calorimetry and dynamic mechanical analysis, respectively. Molecular dynamics simulations were also conducted to investigate the microscopic interactions between sugar molecules and phosphate ions. The hydrogen-bonding characteristics and the self-aggregation features of these mixtures were quantified and compared. Results Thermal analysis measurements demonstrated that the addition of NaH2PO4 decreased both the glass transition temperature and the α-relaxation temperature of the dehydrated trehalose/NaH2PO4 mixture compared to trehalose alone while both Tg and Tα were increased by adding Na2HPO4 to pure trehalose. The hydrogen-bonding interactions between trehalose and HPO42− were found to be stronger than both the trehalose-trehalose hydrogen bonds and those formed between trehalose and H2PO4−. The HPO42− ions also aggregated into smaller clusters than H2PO4− ions. Conclusions The trehalose/Na2HPO4 mixture yielded a higher Tg than pure trehalose because marginally self-aggregated HPO42− ions established a strengthened hydrogen-bonding network with trehalose molecules. In contrast H2PO4− ions served only as plasticizers, resulting in a lower Tg of the mixtures than trehalose alone, creating large-sized ionic pockets, weakening interactions, and disrupting the original hydrogen-bonding network amongst trehalose molecules. PMID:25537342

  9. E6 and E7 from Human Papillomavirus Type 16 Cooperate To Target the PDZ Protein Na/H Exchange Regulatory Factor 1 ▿

    PubMed Central

    Accardi, Rosita; Rubino, Rosa; Scalise, Mariafrancesca; Gheit, Tarik; Shahzad, Naveed; Thomas, Miranda; Banks, Lawrence; Indiveri, Cesare; Sylla, Bakary S.; Cardone, Rosa A.; Reshkin, Stephan J.; Tommasino, Massimo

    2011-01-01

    Previous studies have shown that the PDZ-binding motif of the E6 oncoprotein from the mucosal high-risk (HR) human papillomavirus (HPV) types plays a key role in HPV-mediated cellular transformation in in vitro and in vivo experimental models. HR HPV E6 oncoproteins have the ability to efficiently degrade members of the PDZ motif-containing membrane-associated guanylate kinase (MAGUK) family; however, it is possible that other PDZ proteins are also targeted by E6. Here, we describe a novel interaction of HPV type 16 (HPV16) E6 with a PDZ protein, Na+/H+ exchange regulatory factor 1 (NHERF-1), which is involved in a number of cellular processes, including signaling and transformation. HPV16 E6 associates with and promotes the degradation of NHERF-1, and this property is dependent on the C-terminal PDZ-binding motif of E6. Interestingly, HPV16 E7, via the activation of the cyclin-dependent kinase complexes, promoted the accumulation of a phosphorylated form of NHERF-1, which is preferentially targeted by E6. Thus, both oncoproteins appear to cooperate in targeting NHERF-1. Notably, HPV18 E6 is not able to induce NHERF-1 degradation, indicating that this property is not shared with E6 from all HR HPV types. Downregulation of NHERF-1 protein levels was also observed in HPV16-positive cervical cancer-derived cell lines, such as SiHa and CaSki, as well as HPV16-positive cervical intraepithelial neoplasia (CIN). Finally, our data show that HPV16-mediated NHERF-1 degradation correlates with the activation of the phosphatidylinositol-3′-OH kinase (PI3K)/AKT signaling pathway, which is known to play a key role in carcinogenesis. PMID:21680517

  10. Antecedent hydrogen sulfide elicits an anti-inflammatory phenotype in postischemic murine small intestine: role of BK channels

    PubMed Central

    Zuidema, Mozow Y.; Yang, Yan; Wang, Meifang; Kalogeris, Theodore; Liu, Yajun; Meininger, Cynthia J.; Hill, Michael A.; Davis, Michael J.

    2010-01-01

    The objectives of this study were to determine the role of calcium-activated, small (SK), intermediate (IK), and large (BK) conductance potassium channels in initiating the development of an anti-inflammatory phenotype elicited by preconditioning with an exogenous hydrogen sulfide (H2S) donor, sodium hydrosulfide (NaHS). Intravital microscopy was used to visualize rolling and firmly adherent leukocytes in vessels of the small intestine of mice preconditioned with NaHS (in the absence and presence of SK, IK, and BK channel inhibitors, apamin, TRAM-34, and paxilline, respectively) or SK/IK (NS-309) or BK channel activators (NS-1619) 24 h before ischemia-reperfusion (I/R). I/R induced marked increases in leukocyte rolling and adhesion, effects that were largely abolished by preconditioning with NaHS, NS-309, or NS-1619. The postischemic anti-inflammatory effects of NaHS-induced preconditioning were mitigated by BKB channel inhibitor treatment coincident with NaHS, but not by apamin or TRAM-34, 24 h before I/R. Confocal imaging and immunohistochemistry were used to demonstrate the presence of BKα subunit staining in both endothelial and vascular smooth muscle cells of isolated, pressurized mesenteric venules. Using patch-clamp techniques, we found that BK channels in cultured endothelial cells were activated after exposure to NaHS. Bath application of the same concentration of NaHS used in preconditioning protocols led to a rapid increase in a whole cell K+ current; specifically, the component of K+ current blocked by the selective BK channel antagonist iberiotoxin. The activation of BK current by NaHS could also be demonstrated in single channel recording mode where it was independent of a change in intracellular Ca+ concentration. Our data are consistent with the concept that H2S induces the development of an anti-adhesive state in I/R in part mediated by a BK channel-dependent mechanism. PMID:20833953

  11. Early growth hormone treatment start in childhood growth hormone deficiency improves near adult height: analysis from NordiNet® International Outcome Study.

    PubMed

    Polak, Michel; Blair, Jo; Kotnik, Primoz; Pournara, Effie; Pedersen, Birgitte Tønnes; Rohrer, Tilman R

    2017-11-01

    To investigate the effect of age at growth hormone (GH) treatment start on near adult height (NAH) in children with isolated GH deficiency (GHD). NordiNet® International Outcome Study (IOS) (Nbib960128), a non-interventional, multicentre study, evaluates the long-term effectiveness and safety of Norditropin® (somatropin) (Novo Nordisk A/S) in the real-life clinical setting. Patients ( n  = 172) treated to NAH (height at ≥18 years, or height velocity <2 cm/year at ≥16 (boys) or ≥15 (girls) years) were grouped by age (years) at treatment start (early (girls, <8; boys, <9), intermediate (girls, 8-10; boys, 9-11) or late (girls, >10; boys, >11)) and GHD severity (<3 ng/mL or 3 to ≤10 ng/mL). Multiple regression analysis was used to evaluate the effect of age at treatment start (as a categorical and continuous variable) on NAH standard deviation score (SDS). Age at treatment start had a marked effect on NAH SDS; NAH SDS achieved by patients starting treatment early ( n  = 40 (boys, 70.0%); least squares mean (standard error) -0.76 (0.14)) exceeded that achieved by those starting later (intermediate, n  = 42 (boys, 57.1%); -1.14 (0.15); late, n  = 90 (boys, 68.9%); -1.21 (0.10)). Multiple regression analysis showed a significant association between NAH SDS and age at treatment start ( P  < 0.0242), baseline height SDS (HSDS) ( P  < 0.0001), target HSDS ( P  < 0.0001), and GHD severity ( P  = 0.0012). Most (78.5%) patients achieved a normal NAH irrespective of age at treatment start. Early initiation of GH treatment in children with isolated GHD improves their chance of achieving their genetic height potential. © 2017 The authors.

  12. Hydrogen sulfide promotes autophagy of hepatocellular carcinoma cells through the PI3K/Akt/mTOR signaling pathway.

    PubMed

    Wang, Shanshan S; Chen, Yuhan H; Chen, Ning; Wang, Lijun J; Chen, Dexi X; Weng, Honglei L; Dooley, Steven; Ding, Huiguo G

    2017-03-23

    Hydrogen sulfide (H 2 S), in its gaseous form, plays an important role in tumor carcinogenesis. This study investigated the effects of H 2 S on the cell biological functions of hepatocellular carcinoma (HCC). HCC cell lines, HepG2 and HLE, were treated with NaHS, a donor of H 2 S, and rapamycin, a classic autophagy inducer, for different lengths of time. Western blotting, immunofluorescence, transmission electron microscopy (TEM), scratch assay, CCK-8 and flow cytometric analysis were carried out to examine the effects of H 2 S on HCC autophagy, cell behavior and PI3K/Akt/mTOR signaling. Treatment with NaHS upregulated expression of LC3-II and Atg5, two autophagy-related proteins, in HepG2 and HLE cells. TEM revealed increased numbers of intracellular double-membrane vesicles in those cells treated with NaHS. Like rapamycin, NaHS also significantly inhibited expression of p-PI3K, p-Akt and mTOR proteins in HCC cells. Interestingly, the expression of LC3-II was further increased when the cells were treated with NaHS together with rapamycin. In addition, NaHS inhibited HCC cell migration, proliferation and cell division. These findings show that H 2 S can induce HCC cell apoptosis. The biological function of the gasotransmitter H 2 S in HCC cells was enhanced by the addition of rapamycin. Hydrogen sulfide influences multiple biological functions of HCC cells through inhibiting the PI3K/Akt/mTOR signaling pathway.

  13. Salicylic Acid Is Involved in the Basal Resistance of Tomato Plants to Citrus Exocortis Viroid and Tomato Spotted Wilt Virus

    PubMed Central

    López-Gresa, M. Pilar; Lisón, Purificación; Yenush, Lynne; Conejero, Vicente; Rodrigo, Ismael; Bellés, José María

    2016-01-01

    Tomato plants expressing the NahG transgene, which prevents accumulation of endogenous salicylic acid (SA), were used to study the importance of the SA signalling pathway in basal defence against Citrus Exocortis Viroid (CEVd) or Tomato Spotted Wilt Virus (TSWV). The lack of SA accumulation in the CEVd- or TSWV-infected NahG tomato plants led to an early and dramatic disease phenotype, as compared to that observed in the corresponding parental Money Maker. Addition of acibenzolar-S-methyl, a benzothiadiazole (BTH), which activates the systemic acquired resistance pathway downstream of SA signalling, improves resistance of NahG tomato plants to CEVd and TSWV. CEVd and TSWV inoculation induced the accumulation of the hydroxycinnamic amides p-coumaroyltyramine, feruloyltyramine, caffeoylputrescine, and feruloylputrescine, and the defence related proteins PR1 and P23 in NahG plants earlier and with more intensity than in Money Maker plants, indicating that SA is not essential for the induction of these plant defence metabolites and proteins. In addition, NahG plants produced very high levels of ethylene upon CEVd or TSWV infection when compared with infected Money Maker plants, indicating that the absence of SA produced additional effects on other metabolic pathways. This is the first report to show that SA is an important component of basal resistance of tomato plants to both CEVd and TSWV, indicating that SA-dependent defence mechanisms play a key role in limiting the severity of symptoms in CEVd- and TSWV-infected NahG tomato plants. PMID:27893781

  14. Translation, cross-cultural adaptation and validation of the Brazilian version of the Nonarthritic Hip Score.

    PubMed

    Del Castillo, Letícia Nunes Carreras; Leporace, Gustavo; Cardinot, Themis Moura; Levy, Roger Abramino; Oliveira, Liszt Palmeira de

    2013-01-01

    CONTEXT AND OBJECTIVE The Nonarthritic Hip Score (NAHS) is a clinical evaluation questionnaire that was developed in the English language to evaluate hip function in young and physically active patients. The aims of this study were to translate this questionnaire into the Brazilian Portuguese language, to adapt it to Brazilian culture and to validate it. DESIGN AND SETTING Cohort study conducted between 2008 and 2010, at Universidade do Estado do Rio de Janeiro (UERJ). METHODS Questions about physical activities and household chores were modified to better fit Brazilian culture. Reproducibility, internal consistency and validity (correlations with the Algofunctional Lequesne Index and the Western Ontario and McMaster Universities Arthritis Index [WOMAC]) were tested. The NAHS-Brazil, Lequesne and WOMAC questionnaires were applied to 64 young and physically active patients (mean age, 40.9 years; 31 women). RESULTS The intraclass correlation coefficient (which measures reproducibility) was 0.837 (P < 0.001). Bland-Altman plots revealed a mean error in the difference between the two measurements of 0.42. The internal consistency was confirmed through a Cronbach alpha of 0.944. The validity between NAHS-Brazil and Lequesne and between NAHS-Brazil and WOMAC showed high correlations, r = 0.7340 and r = 0.9073, respectively. NAHS-Brazil showed good validity with no floor or ceiling effects. CONCLUSION The NAHS was translated into the Brazilian Portuguese language and was cross-culturally adapted to Brazilian culture. It was shown to be a useful tool in clinical practice for assessing the quality of life of young and physically active patients with hip pain.

  15. An experimental comparison of various methods of nearfield acoustic holography

    DOE PAGES

    Chelliah, Kanthasamy; Raman, Ganesh; Muehleisen, Ralph T.

    2017-05-19

    An experimental comparison of four different methods of nearfield acoustic holography (NAH) is presented in this study for planar acoustic sources. The four NAH methods considered in this study are based on: (1) spatial Fourier transform, (2) equivalent sources model, (3) boundary element methods and (4) statistically optimized NAH. Two dimensional measurements were obtained at different distances in front of a tonal sound source and the NAH methods were used to reconstruct the sound field at the source surface. Reconstructed particle velocity and acoustic pressure fields presented in this study showed that the equivalent sources model based algorithm along withmore » Tikhonov regularization provided the best localization of the sources. Reconstruction errors were found to be smaller for the equivalent sources model based algorithm and the statistically optimized NAH algorithm. Effect of hologram distance on the performance of various algorithms is discussed in detail. The study also compares the computational time required by each algorithm to complete the comparison. Four different regularization parameter choice methods were compared. The L-curve method provided more accurate reconstructions than the generalized cross validation and the Morozov discrepancy principle. Finally, the performance of fixed parameter regularization was comparable to that of the L-curve method.« less

  16. An experimental comparison of various methods of nearfield acoustic holography

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Chelliah, Kanthasamy; Raman, Ganesh; Muehleisen, Ralph T.

    An experimental comparison of four different methods of nearfield acoustic holography (NAH) is presented in this study for planar acoustic sources. The four NAH methods considered in this study are based on: (1) spatial Fourier transform, (2) equivalent sources model, (3) boundary element methods and (4) statistically optimized NAH. Two dimensional measurements were obtained at different distances in front of a tonal sound source and the NAH methods were used to reconstruct the sound field at the source surface. Reconstructed particle velocity and acoustic pressure fields presented in this study showed that the equivalent sources model based algorithm along withmore » Tikhonov regularization provided the best localization of the sources. Reconstruction errors were found to be smaller for the equivalent sources model based algorithm and the statistically optimized NAH algorithm. Effect of hologram distance on the performance of various algorithms is discussed in detail. The study also compares the computational time required by each algorithm to complete the comparison. Four different regularization parameter choice methods were compared. The L-curve method provided more accurate reconstructions than the generalized cross validation and the Morozov discrepancy principle. Finally, the performance of fixed parameter regularization was comparable to that of the L-curve method.« less

  17. Effects of hydrogen sulfide on hemodynamics, inflammatory response and oxidative stress during resuscitated hemorrhagic shock in rats

    PubMed Central

    2010-01-01

    Introduction Hydrogen sulfide (H2S) has been shown to improve survival in rodent models of lethal hemorrhage. Conversely, other authors have reported that inhibition of endogenous H2S production improves hemodynamics and reduces organ injury after hemorrhagic shock. Since all of these data originate from unresuscitated models and/or the use of a pre-treatment design, we therefore tested the hypothesis that the H2S donor, sodium hydrosulfide (NaHS), may improve hemodynamics in resuscitated hemorrhagic shock and attenuate oxidative and nitrosative stresses. Methods Thirty-two rats were mechanically ventilated and instrumented to measure mean arterial pressure (MAP) and carotid blood flow (CBF). Animals were bled during 60 minutes in order to maintain MAP at 40 ± 2 mm Hg. Ten minutes prior to retransfusion of shed blood, rats randomly received either an intravenous bolus of NaHS (0.2 mg/kg) or vehicle (0.9% NaCl). At the end of the experiment (T = 300 minutes), blood, aorta and heart were harvested for Western blot (inductible Nitric Oxyde Synthase (iNOS), Nuclear factor-κB (NF-κB), phosphorylated Inhibitor κB (P-IκB), Inter-Cellular Adhesion Molecule (I-CAM), Heme oxygenase 1(HO-1), Heme oxygenase 2(HO-2), as well as nuclear respiratory factor 2 (Nrf2)). Nitric oxide (NO) and superoxide anion (O2-) were also measured by electron paramagnetic resonance. Results At the end of the experiment, control rats exhibited a decrease in MAP which was attenuated by NaHS (65 ± 32 versus 101 ± 17 mmHg, P < 0.05). CBF was better maintained in NaHS-treated rats (1.9 ± 1.6 versus 4.4 ± 1.9 ml/minute P < 0.05). NaHS significantly limited shock-induced metabolic acidosis. NaHS also prevented iNOS expression and NO production in the heart and aorta while significantly reducing NF-kB, P-IκB and I-CAM in the aorta. Compared to the control group, NaHS significantly increased Nrf2, HO-1 and HO-2 and limited O2- release in both aorta and heart (P < 0.05). Conclusions NaHS is

  18. Sarcolemmal localisation of Na+/H+ exchange and Na+–HCO3− co-transport influences the spatial regulation of intracellular pH in rat ventricular myocytes

    PubMed Central

    Garciarena, Carolina D; Ma, Yu-ling; Swietach, Pawel; Huc, Laurence; Vaughan-Jones, Richard D

    2013-01-01

    Membrane acid extrusion by Na+/H+ exchange (NHE1) and Na+–HCO3− co-transport (NBC) is essential for maintaining a low cytoplasmic [H+] (∼60 nm, equivalent to an intracellular pH (pHi) of 7.2). This protects myocardial function from the high chemical reactivity of H+ ions, universal end-products of metabolism. We show here that, in rat ventricular myocytes, fluorescent antibodies map the NBC isoforms NBCe1 and NBCn1 to lateral sarcolemma, intercalated discs and transverse tubules (t-tubules), while NHE1 is absent from t-tubules. This unexpected difference matches functional measurements of pHi regulation (using AM-loaded SNARF-1, a pH fluorophore). Thus, myocyte detubulation (by transient exposure to 1.5 m formamide) reduces global acid extrusion on NBC by 40%, without affecting NHE1. Similarly, confocal pHi imaging reveals that NBC stimulation induces spatially uniform pHi recovery from acidosis, whereas NHE1 stimulation induces pHi non-uniformity during recovery (of ∼0.1 units, for 2–3 min), particularly at the ends of the cell where intercalated discs are commonly located, and where NHE1 immunostaining is prominent. Mathematical modelling shows that this induction of local pHi microdomains is favoured by low cytoplasmic H+ mobility and long H+ diffusion distances, particularly to surface NHE1 transporters mediating high membrane flux. Our results provide the first evidence for a spatial localisation of [H+]i regulation in ventricular myocytes, suggesting that, by guarding pHi, NHE1 preferentially protects gap junctional communication at intercalated discs, while NBC locally protects t-tubular excitation–contraction coupling. PMID:23420656

  19. Escherichia coli Heat-Stable Enterotoxin Mediates Na+/H+ Exchanger 4 Inhibition Involving cAMP in T84 Human Intestinal Epithelial Cells.

    PubMed

    Beltrán, Ana R; Carraro-Lacroix, Luciene R; Bezerra, Camila N A; Cornejo, Marcelo; Norambuena, Katrina; Toledo, Fernando; Araos, Joaquín; Pardo, Fabián; Leiva, Andrea; Sanhueza, Carlos; Malnic, Gerhard; Sobrevia, Luis; Ramírez, Marco A

    2015-01-01

    The enterotoxigenic Escherichia coli strains lead to diarrhoea in humans due to heat-labile and heat-stable (STa) enterotoxins. STa increases Cl-release in intestinal cells, including the human colonic carcinoma T84 cell line, involving increased cGMP and membrane alkalization due to reduced Na+/H+ exchangers (NHEs) activity. Since NHEs modulate intracellular pH (pHi), and NHE1, NHE2, and NHE4 are expressed in T84 cells, we characterized the STa role as modulator of these exchangers. pHi was assayed by the NH4Cl pulse technique and measured by fluorescence microscopy in BCECF-preloaded cells. pHi recovery rate (dpHi/dt) was determined in the absence or presence of 0.25 μmol/L STa (30 minutes), 25 μmol/L HOE-694 (concentration inhibiting NHE1 and NHE2), 500 μmol/L sodium nitroprusside (SNP, spontaneous nitric oxide donor), 100 μmol/L dibutyryl cyclic GMP (db-cGMP), 100 nmol/L H89 (protein kinase A inhibitor), or 10 μmol/L forskolin (adenylyl cyclase activator). cGMP and cAMP were measured in cell extracts by radioimmunoassay, and buffering capacity (ßi) and H+ efflux (JH+) was determined. NHE4 protein abundance was determined by western blotting. STa and HOE-694 caused comparable reduction in dpHi/dt and JH+ (~63%), without altering basal pHi (range 7.144-7.172). STa did not alter ßi value in a range of 1.6 pHi units. The dpHi/dt and JH+ was almost abolished (~94% inhibition) by STa + HOE-694. STa effect was unaltered by db-cGMP or SNP. However, STa and forskolin increased cAMP level. STa-decreased dpHi/dt and JH+ was mimicked by forskolin, and STa + HOE-694 effect was abolished by H89. Thus, incubation of T84 cells with STa results in reduced NHE4 activity leading to a lower capacity of pHi recovery requiring cAMP, but not cGMP. STa effect results in a causal phenomenon (STa/increased cAMP/increased PKA activity/reduced NHE4 activity) ending with intracellular acidification that could have consequences in the gastrointestinal cells function promoting human

  20. Escherichia coli Heat-Stable Enterotoxin Mediates Na+/H+ Exchanger 4 Inhibition Involving cAMP in T84 Human Intestinal Epithelial Cells

    PubMed Central

    Beltrán, Ana R.; Carraro-Lacroix, Luciene R.; Bezerra, Camila N. A.; Cornejo, Marcelo; Norambuena, Katrina; Toledo, Fernando; Araos, Joaquín; Pardo, Fabián; Leiva, Andrea; Sanhueza, Carlos; Malnic, Gerhard; Sobrevia, Luis; Ramírez, Marco A.

    2015-01-01

    The enterotoxigenic Escherichia coli strains lead to diarrhoea in humans due to heat-labile and heat-stable (STa) enterotoxins. STa increases Cl-release in intestinal cells, including the human colonic carcinoma T84 cell line, involving increased cGMP and membrane alkalization due to reduced Na+/H+ exchangers (NHEs) activity. Since NHEs modulate intracellular pH (pHi), and NHE1, NHE2, and NHE4 are expressed in T84 cells, we characterized the STa role as modulator of these exchangers. pHi was assayed by the NH4Cl pulse technique and measured by fluorescence microscopy in BCECF–preloaded cells. pHi recovery rate (dpHi/dt) was determined in the absence or presence of 0.25 μmol/L STa (30 minutes), 25 μmol/L HOE-694 (concentration inhibiting NHE1 and NHE2), 500 μmol/L sodium nitroprusside (SNP, spontaneous nitric oxide donor), 100 μmol/L dibutyryl cyclic GMP (db-cGMP), 100 nmol/L H89 (protein kinase A inhibitor), or 10 μmol/L forskolin (adenylyl cyclase activator). cGMP and cAMP were measured in cell extracts by radioimmunoassay, and buffering capacity (ßi) and H+ efflux (J H +) was determined. NHE4 protein abundance was determined by western blotting. STa and HOE-694 caused comparable reduction in dpHi/dt and J H + (~63%), without altering basal pHi (range 7.144–7.172). STa did not alter ßi value in a range of 1.6 pHi units. The dpHi/dt and J H + was almost abolished (~94% inhibition) by STa + HOE-694. STa effect was unaltered by db-cGMP or SNP. However, STa and forskolin increased cAMP level. STa–decreased dpHi/dt and J H + was mimicked by forskolin, and STa + HOE-694 effect was abolished by H89. Thus, incubation of T84 cells with STa results in reduced NHE4 activity leading to a lower capacity of pHi recovery requiring cAMP, but not cGMP. STa effect results in a causal phenomenon (STa/increased cAMP/increased PKA activity/reduced NHE4 activity) ending with intracellular acidification that could have consequences in the gastrointestinal cells function

  1. Hydrogen sulfide protects endothelial nitric oxide function under conditions of acute oxidative stress in vitro.

    PubMed

    Al-Magableh, Mohammad R; Kemp-Harper, Barbara K; Ng, Hooi H; Miller, Alyson A; Hart, Joanne L

    2014-01-01

    The aim of this study was to examine the ability of H2S, released from NaHS to protect vascular endothelial function under conditions of acute oxidative stress by scavenging superoxide anions (O2(-)) and suppressing vascular superoxide anion production. O2(-) was generated in Krebs' solution by reacting hypoxanthine with xanthine oxidase (Hx-XO) or with the O2(-) generator pyrogallol to model acute oxidative stress in vitro. O2(-) generation was measured by lucigenin-enhanced chemiluminescence. Functional responses in mouse aortic rings were assessed using a small vessel myograph. NaHS scavenged O2(-) in a concentration-dependent manner. Isolated aortic rings exposed to either Hx-XO or pyrogallol displayed significantly attenuated maximum vasorelaxation responses to the endothelium-dependent vasodilator acetylcholine, and significantly reduced NO bioavailability, which was completely reversed if vessels were pre-incubated with NaHS (100 μM). NADPH-stimulated aortic O2(-) production was significantly attenuated by the NADPH oxidase inhibitor diphenyl iodonium. Prior treatment of vessels with NaHS (100 nM-100 μM; 30 min) inhibited NADPH-stimulated aortic O2(-) production in a concentration-dependent manner. This effect persisted when NaHS was washed out prior to measuring NADPH-stimulated O2(-) production. These data show for the first time that NaHS directly scavenges O2(-) and suppresses vascular NADPH oxidase-derived O2(-) production in vitro. Furthermore, these properties protect endothelial function and NO bioavailability in an in vitro model of acute oxidative stress. These results suggest that H2S can elicit vasoprotection by both scavenging O2(-) and by reducing vascular NADPH oxidase-derived O2(-) production.

  2. Effects of hydrogen sulphide on motility patterns in the rat colon

    PubMed Central

    Gil, V; Parsons, SP; Gallego, D; Huizinga, JD; Jimenez, M

    2013-01-01

    Background and Purpose Hydrogen sulphide (H2S) is an endogenous gaseous signalling molecule with putative functions in gastrointestinal motility regulation. Characterization of H2S effects on colonic motility is crucial to establish its potential use as therapeutic agent in the treatment of colonic disorders. Experimental Approach H2S effects on colonic motility were characterized using video recordings and construction of spatio-temporal maps. Microelectrode and muscle bath studies were performed to investigate the mechanisms underlying H2S effects. NaHS was used as the source of H2S. Key Results Rhythmic propulsive motor complexes (RPMCs) and ripples were observed in colonic spatio-temporal maps. Serosal addition of NaHS concentration-dependently inhibited RPMCs. In contrast, NaHS increased amplitude of the ripples without changing their frequency. Therefore, ripples became the predominant motor pattern. Neuronal blockade with lidocaine inhibited RPMCs, which were restored after administration of carbachol. Subsequent addition of NaHS inhibited RPMCs. Luminal addition of NaHS did not modify motility patterns. NaHS inhibited cholinergic excitatory junction potentials, carbachol-induced contractions and hyperpolarized smooth muscle cells, but did not modify slow wave activity. Conclusions and Implications H2S modulated colonic motility inhibiting propulsive contractile activity and enhancing the amplitude of ripples, promoting mixing. Muscle hyperpolarization and inhibition of neurally mediated cholinergic responses contributed to the inhibitory effect on propulsive activity. H2S effects were not related to changes in the frequency of slow wave activity originating in the network of interstitial cells of Cajal located near the submuscular plexus. Luminal H2S did not modify colonic motility probably because of epithelial detoxification. PMID:23297830

  3. Hydrogen sulfide inhibits high glucose-induced NADPH oxidase 4 expression and matrix increase by recruiting inducible nitric oxide synthase in kidney proximal tubular epithelial cells.

    PubMed

    Lee, Hak Joo; Lee, Doug Yoon; Mariappan, Meenalakshmi M; Feliers, Denis; Ghosh-Choudhury, Goutam; Abboud, Hanna E; Gorin, Yves; Kasinath, Balakuntalam S

    2017-04-07

    High-glucose increases NADPH oxidase 4 (NOX4) expression, reactive oxygen species generation, and matrix protein synthesis by inhibiting AMP-activated protein kinase (AMPK) in renal cells. Because hydrogen sulfide (H 2 S) inhibits high glucose-induced matrix protein increase by activating AMPK in renal cells, we examined whether H 2 S inhibits high glucose-induced expression of NOX4 and matrix protein and whether H 2 S and NO pathways are integrated. High glucose increased NOX4 expression and activity at 24 h in renal proximal tubular epithelial cells, which was inhibited by sodium hydrosulfide (NaHS), a source of H 2 S. High glucose decreased AMPK phosphorylation and activity, which was restored by NaHS. Compound C, an AMPK inhibitor, prevented NaHS inhibition of high glucose-induced NOX4 expression. NaHS inhibition of high glucose-induced NOX4 expression was abrogated by N (ω)-nitro-l-arginine methyl ester, an inhibitor of NOS. NaHS unexpectedly augmented the expression of inducible NOS (iNOS) but not endothelial NOS. iNOS siRNA and 1400W, a selective iNOS inhibitor, abolished the ameliorative effects of NaHS on high glucose-induced NOX4 expression, reactive oxygen species generation, and, matrix laminin expression. Thus, H 2 S recruits iNOS to generate NO to inhibit high glucose-induced NOX4 expression, oxidative stress, and matrix protein accumulation in renal epithelial cells; the two gasotransmitters H 2 S and NO and their interaction may serve as therapeutic targets in diabetic kidney disease. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  4. Hydrogen Sulfide Preconditioning Protects Rat Liver against Ischemia/Reperfusion Injury by Activating Akt-GSK-3β Signaling and Inhibiting Mitochondrial Permeability Transition

    PubMed Central

    Zhang, Hao; Xu, Fengying; Zou, Zui; Liu, Meng; Wang, Quanxing; Miao, Mingyong; Shi, Xueyin

    2013-01-01

    Hydrogen sulfide (H2S) is the third most common endogenously produced gaseous signaling molecule, but its impact on hepatic ischemia/reperfusion (I/R) injury, especially on mitochondrial function, remains unclear. In this study, rats were randomized into Sham, I/R, ischemia preconditioning (IPC) or sodium hydrosulfide (NaHS, an H2S donor) preconditioning groups. To establish a model of segmental (70%) warm hepatic ischemia, the hepatic artery, left portal vein and median liver lobes were occluded for 60 min and then unclamped to allow reperfusion. Preconditioning with 12.5, 25 or 50 μmol/kg NaHS prior to the I/R insult significantly increased serum H2S levels, and, similar to IPC, NaHS preconditioning decreased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in the plasma and prevented hepatocytes from undergoing I/R-induced necrosis. Moreover, a sub-toxic dose of NaHS (25 μmol/kg) did not disrupt the systemic hemodynamics but dramatically inhibited mitochondrial permeability transition pore (MPTP) opening and thus prevented mitochondrial-related cell death and apoptosis. Mechanistic studies revealed that NaHS preconditioning markedly increased the expression of phosphorylated protein kinase B (p-Akt), phosphorylated glycogen synthase kinase-3 beta (p-GSK-3β) and B-cell lymphoma-2 (Bcl-2) and decreased the release of mitochondrial cytochrome c and cleaved caspase-3/9 levels. Therefore, NaHS administration prior to hepatic I/R ameliorates mitochondrial and hepatocellular damage through the inhibition of MPTP opening and the activation of Akt-GSK-3β signaling. Furthermore, this study provides experimental evidence for the clinical use of H2S to reduce liver damage after perioperative I/R injury. PMID:24058562

  5. Hydrogen Sulfide Treatment Promotes Glucose Uptake by Increasing Insulin Receptor Sensitivity and Ameliorates Kidney Lesions in Type 2 Diabetes

    PubMed Central

    Xue, Rong; Hao, Dan-Dan; Sun, Ji-Ping; Li, Wen-Wen; Zhao, Man-Man; Li, Xing-Hui; Chen, Ying; Zhu, Jian-Hua; Ding, Ying-Jiong; Liu, Jun

    2013-01-01

    Abstract Aims: To examine if hydrogen sulfide (H2S) can promote glucose uptake and provide amelioration in type 2 diabetes. Results: Treatment with sodium hydrosulfide (NaHS, an H2S donor) increased glucose uptake in both myotubes and adipocytes. The H2S gas solution showed similar effects. The NaHS effects were blocked by an siRNA-mediated knockdown of the insulin receptor (IR). NaHS also increased phosphorylation of the IR, PI3K, and Akt. In Goto-Kakizaki (GK) diabetic rats, chronic NaHS treatment (30 μmol·kg−1·day−1) decreased fasting blood glucose, increased insulin sensitivity, and increased glucose tolerance with increased phosphorylation of PI3K and Akt in muscles. Similar insulin-sensitizing effects of NaHS treatment were also observed in Wistar rats. Moreover, glucose uptake was reduced in the cells with siRNA-mediated knockdown of the H2S-generating enzyme cystathionine γ-lyase in the presence or absence of exogenous H2S. Moreover, chronic NaHS treatment reduced oxygen species and the number of crescentic glomeruli in the kidney of GK rats. Innovation and Conclusion: This study provides the first piece of evidence for the insulin-sensitizing effect of NaHS/H2S in the both in vitro and in vivo models of insulin resistance. Rebound Track: This work was rejected during a standard peer review and rescued by the Rebound Peer Review (Antoxid Redox Signal 16: 293–296, 2012) with the following serving as open reviewers: Jin-Song Bian, Samuel Dudley, Hideo Kimura, and Xian Wang. Antioxid. Redox Signal. 19, 5–23. PMID:23293908

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

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Rivera, Alicia; De Franceschi, Lucia; Peters, Luanne L.

    2006-06-02

    Moderate hemolytic anemia, abnormal erythrocyte morphology(spherocytosis), and decreased membrane stability are observed in micewith complete deficiency of all erythroid protein 4.1 protein isoforms(4.1-/-; Shi TS et al., J. Clin. Invest. 103:331,1999). We have examinedthe effects of erythroid protein 4.1 (4.1R) deficiency on erythrocytecation transport and volume regulation. 4.1-/- mice exhibited erythrocytedehydration that was associated with reduced cellular K and increased Nacontent. Increased Na permeability was observed in these mice, mostlymediated by Na/H exchange with normal Na-K pump and Na-K-2Cl cotransportactivities. The Na/H exchange of 4.1-/- erythrocytes was markedlyactivated by exposure to hypertonic conditions (18.2+- 3.2 in 4.1 -/- vs.9.8 +-more » 1.3 mmol/1013 cell x h in control mice), with an abnormaldependence on osmolarity, (K0.5=417 +- 42 in 4.1 -/- vs. 460 +- 35 mOsmin control mice) suggestive of an up-regulated functional state. Whilethe affinity for 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 91.47Moderatehemolytic anemia, abnormal erythrocyte morphology (spherocytosis), anddecreased membrane stability are observed in mice with completedeficiency of all erythroid protein 4.1 protein isoforms (4.1-/-; Shi TSet al., J. Clin. Invest. 103:331,1999). We have examined the effects oferythroid protein 4.1 (4.1R) deficiency on erythrocyte cation transportand volume regulation. 4.1-/- mice exhibited erythrocyte dehydration thatwas associated with reduced cellular K and increased Na content.Increased Na permeability was observed in these mice, mostly mediated byNa/H exchange with normal Na-K pump and Na-K-2Cl cotransport activities.The Na/H exchange of 4.1-/- erythrocytes was markedly activated byexposure to hypertonic conditions (18.2 +- 3.2 in 4.1 -/- vs. 9.8 +- 1.3mmol/1013 cell x h in control mice

  7. Increased Na+/H+ exchanger activity on the apical surface of a cilium-deficient cortical collecting duct principal cell model of polycystic kidney disease

    PubMed Central

    Olteanu, Dragos; Liu, Xiaofen; Liu, Wen; Roper, Venus C.; Sharma, Neeraj; Yoder, Bradley K.; Satlin, Lisa M.; Schwiebert, Erik M.

    2012-01-01

    Pathophysiological anomalies in autosomal dominant and recessive forms of polycystic kidney disease (PKD) may derive from impaired function/formation of the apical central monocilium of ductal epithelia such as that seen in the Oak Ridge polycystic kidney or orpk (Ift88Tg737Rpw) mouse and its immortalized cell models for the renal collecting duct. According to a previous study, Na/H exchanger (NHE) activity may contribute to hyperabsorptive Na+ movement in cilium-deficient (“mutant”) cortical collecting duct principal cell monolayers derived from the orpk mice compared with cilium-competent (“rescued”) monolayers. To examine NHE activity, we measured intracellular pH (pHi) by fluorescence imaging with the pH-sensitive dye BCECF, and used a custom-designed perfusion chamber to control the apical and basolateral solutions independently. Both mutant and rescued monolayers exhibited basolateral Na+-dependent acid-base transporter activity in the nominal absence of CO2/HCO3−. However, only the mutant cells displayed appreciable apical Na+-induced pHi recoveries from NH4+ prepulse-induced acid loads. Similar results were obtained with isolated, perfused collecting ducts from orpk vs. wild-type mice. The pHi dependence of basolateral cariporide/HOE-694-sensitive NHE activity under our experimental conditions was similar in both mutant and rescued cells, and 3.5- to 4.5-fold greater than apical HOE-sensitive NHE activity in the mutant cells (pHi 6.23–6.68). Increased apical NHE activity correlated with increased apical NHE1 expression in the mutant cells, and increased apical localization in collecting ducts of kidney sections from orpk vs. control mice. A kidney-specific conditional cilium-knockout mouse produced a more acidic urine compared with wild-type littermates and became alkalotic by 28 days of age. This study provides the first description of altered NHE activity, and an associated acid-base anomaly in any form of PKD. PMID:22301060

  8. An experimental study of Pb and Zn as a function of HCl at 300 and 500°C

    NASA Astrophysics Data System (ADS)

    Rock, M.; Frank, M. R.

    2017-12-01

    Hydrothermal galena (PbS) and sphalerite (ZnS) deposits are important sources of Pb and Zn and can be related to low-temperature Mississippi Valley (MVT), moderate temperature massive sulfides (VMS), and higher-temperature porphyry type deposits). Lead and Zn are thought to complex with chloride (PbCl2 and ZnCl2) in the hydrothermal fluid and can precipitate through a decrease in temperature, an increase in pH, or through the addition of reduce sulfur. There is, however, a dearth of data on the solubility of galena and sphalerite in acidic and sulfur-rich hydrothermal fluids over a range temperature that spans the MVT to porphyry systems The experiments were conducted in René 41 cold-seal pressure vessels at 300 and 500°C and 100 MPa to determine the concentrations of Pb and Zn in hydrothermal fluids as a function of HCl. Platinum capsules were loaded with natural galena and sphalerite and an aqueous fluid of 13-15 wt.% NaCl (eq.) containing HCl + NaCl. The [Na/H] of the aqueous fluid was varied from 1.75 to 340. The aqueous fluids were captured at the conclusion of the experiment and Pb and Zn concentrations were determined by using AA and ICP-OES. The data illustrate that the concentration of Pb and Zn in the fluid increased directly with temperature and total chloride while indirectly with [Na/H]. Lead and Zn concentrations at 300°C were highest at a [Na/H] of 1.75 with concentrations of 84 μg/g and 2200 ± 600 μg/g, respectively, and decreased to 4 μg/g and 241 μg/g, respectively, at a [Na/H] of 295. At 500°C, lead concentrations were 7600 ± 1600 μg/g at a [Na/H] of 1.75 and decreased to 1170 μg/g at a [Na/H] of 340. Zinc concentrations at 500°C were 1700 μg/g at a [Na/H] of 30 and 640 μg/g at a [Na/H] of 100. Decreasing acidity (increasing [Na/H]) and temperature are especially efficient at inducing the precipitation of galena and sphalerite and could produce variable Pb:Zn values in a given system depending on if temperature or acidity was more

  9. Statistische Physik

    NASA Astrophysics Data System (ADS)

    Fließbach, Torsten

    In der Statistischen Physik befassen wir uns mit Systemen aus sehr vielen Teilchen. Beispiele hierfür sind die Atome eines Gases oder einer Flüssigkeit, die Phononen eines Festkörpers oder die Photonen in einem Plasma. Die Gesetze für die Bewegung einzelner Teilchen sind durch die Mechanik oder die Quantenmechanik gegeben. Aufgrund der großen Zahl der Teilchen (zum Beispiel N = 6 • 1023 für ein Mol eines Gases) sind die Bewegungsgleichungen jedoch nicht auswertbar. Das Ergebnis einer solchen Auswertung, also etwa die Bahnen von 6•1023 Teilchen, wäre auch uninteressant und irrelevant. Die Behandlung dieser Systeme erfolgt daher statistisch, das heißt auf der Grundlage von Annahmen über dieWahrscheinlichkeit verschiedener Bahnen oder Zustände.

  10. Hydrogen sulfide ameliorates aging-associated changes in the kidney.

    PubMed

    Lee, Hak Joo; Feliers, Denis; Barnes, Jeffrey L; Oh, Sae; Choudhury, Goutam Ghosh; Diaz, Vivian; Galvan, Veronica; Strong, Randy; Nelson, James; Salmon, Adam; Kevil, Christopher G; Kasinath, Balakuntalam S

    2018-04-01

    Aging is associated with replacement of normal kidney parenchyma by fibrosis. Because hydrogen sulfide (H 2 S) ameliorates kidney fibrosis in disease models, we examined its status in the aging kidney. In the first study, we examined kidney cortical H 2 S metabolism and signaling pathways related to synthesis of proteins including matrix proteins in young and old male C57BL/6 mice. In old mice, increase in renal cortical content of matrix protein involved in fibrosis was associated with decreased H 2 S generation and AMPK activity, and activation of insulin receptor (IR)/IRS-2-Akt-mTORC1-mRNA translation signaling axis that can lead to increase in protein synthesis. In the second study, we randomized 18-19 month-old male C57BL/6 mice to receive 30 μmol/L sodium hydrosulfide (NaHS) in drinking water vs. water alone (control) for 5 months. Administration of NaHS increased plasma free sulfide levels. NaHS inhibited the increase in kidney cortical content of matrix proteins involved in fibrosis and ameliorated glomerulosclerosis. NaHS restored AMPK activity and inhibited activation of IR/IRS-2-Akt-mTORC1-mRNA translation axis. NaHS inhibited age-related increase in kidney cortical content of p21, IL-1β, and IL-6, components of the senescence-associated secretory phenotype. NaHS abolished increase in urinary albumin excretion seen in control mice and reduced serum cystatin C levels suggesting improved glomerular clearance function. We conclude that aging-induced changes in the kidney are associated with H 2 S deficiency. Administration of H 2 S ameliorates aging-induced kidney changes probably by inhibiting signaling pathways leading to matrix protein synthesis.

  11. Patch nearfield acoustic holography combined with sound field separation technique applied to a non-free field

    NASA Astrophysics Data System (ADS)

    Bi, ChuanXing; Jing, WenQian; Zhang, YongBin; Xu, Liang

    2015-02-01

    The conventional nearfield acoustic holography (NAH) is usually based on the assumption of free-field conditions, and it also requires that the measurement aperture should be larger than the actual source. This paper is to focus on the problem that neither of the above-mentioned requirements can be met, and to examine the feasibility of reconstructing the sound field radiated by partial source, based on double-layer pressure measurements made in a non-free field by using patch NAH combined with sound field separation technique. And also, the sensitivity of the reconstructed result to the measurement error is analyzed in detail. Two experiments involving two speakers in an exterior space and one speaker inside a car cabin are presented. The experimental results demonstrate that the patch NAH based on single-layer pressure measurement cannot obtain a satisfied result due to the influences of disturbing sources and reflections, while the patch NAH based on double-layer pressure measurements can successfully remove these influences and reconstruct the patch sound field effectively.

  12. Enhanced Reactive Oxygen Species Production, Acidic Cytosolic pH and Upregulated Na+/H+ Exchanger (NHE) in Dicer Deficient CD4+ T Cells.

    PubMed

    Singh, Yogesh; Zhou, Yuetao; Zhang, Shaqiu; Abdelazeem, Khalid N M; Elvira, Bernat; Salker, Madhuri S; Lang, Florian

    2017-01-01

    MicroRNAs (miRNAs) negatively regulate gene expression at a post-transcriptional level. Dicer, a cytoplasmic RNase III enzyme, is required for the maturation of miRNAs from precursor miRNAs. Dicer, therefore, is a critical enzyme involved in the biogenesis and processing of miRNAs. Several biological processes are controlled by miRNAs, including the regulation of T cell development and function. T cells generate reactive oxygen species (ROS) with parallel H+ extrusion accomplished by the Na+/H+-exchanger 1 (NHE1). The present study explored whether ROS production, as well as NHE1 expression and function are sensitive to the lack of Dicer (miRNAs deficient) and could be modified by individual miRNAs. CD4+ T cells were isolated from CD4 specific Dicer deficient (DicerΔ/Δ) mice and the respective control mice (Dicerfl/fl). Transcript and protein levels were quantified with RT-PCR and Western blotting, respectively. For determination of intracellular pH (pHi) cells were incubated with the pH sensitive dye bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein (BCECF) and Na+/H+ exchanger (NHE) activity was calculated from re-alkalinization after an ammonium pulse. Changes in cell volume were measured using the forward scatter in flow cytometry, and ROS production utilizing 2',7' -dichlorofluorescin diacetate (DCFDA) fluorescence. Transfection of miRNA-control and mimics in T cells was performed using DharmaFECT3 reagent. ROS production, cytosolic H+ concentration, NHE1 transcript and protein levels, NHE activity, and cell volume were all significantly higher in CD4+ T cells from DicerΔ/Δ mice than in CD4+ T cells from Dicerfl/fl mice. Furthermore, individual miR-200b and miR-15b modify pHi and NHE activity in Dicerfl/fl and DicerΔ/Δ CD4+ T cells, respectively. Lack of Dicer leads to oxidative stress, cytosolic acidification, upregulated NHE1 expression and activity as well as swelling of CD4+ T cells, functions all reversed by miR-15b or miR-200b. © 2017 The Author

  13. Involvement of ERK in NMDA receptor-independent cortical neurotoxicity of hydrogen sulfide

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kurokawa, Yuko; Sekiguchi, Fumiko; Kubo, Satoko

    2011-11-04

    Highlights: Black-Right-Pointing-Pointer Hydrogen sulfide causes NMDA receptor-independent neurotoxicity in mouse fetal cortical neurons. Black-Right-Pointing-Pointer Activation of ERK mediates the toxicity of hydrogen sulfide. Black-Right-Pointing-Pointer Apoptotic mechanisms are involved in the hydrogen-induced cell death. -- Abstract: Hydrogen sulfide (H{sub 2}S), a gasotransmitter, exerts both neurotoxicity and neuroprotection, and targets multiple molecules including NMDA receptors, T-type calcium channels and NO synthase (NOS) that might affect neuronal viability. Here, we determined and characterized effects of NaHS, an H{sub 2}S donor, on cell viability in the primary cultures of mouse fetal cortical neurons. NaHS caused neuronal death, as assessed by LDH release and trypanmore » blue staining, but did not significantly reduce the glutamate toxicity. The neurotoxicity of NaHS was resistant to inhibitors of NMDA receptors, T-type calcium channels and NOS, and was blocked by inhibitors of MEK, but not JNK, p38 MAP kinase, PKC and Src. NaHS caused prompt phosphorylation of ERK and upregulation of Bad, followed by translocation of Bax to mitochondria and release of mitochondrial cytochrome c, leading to the nuclear condensation/fragmentation. These effects of NaHS were suppressed by the MEK inhibitor. Our data suggest that the NMDA receptor-independent neurotoxicity of H{sub 2}S involves activation of the MEK/ERK pathway and some apoptotic mechanisms.« less

  14. Osteogenic Differentiation of Human and Ovine Bone Marrow Stromal Cells in response to β-Glycerophosphate and Monosodium Phosphate.

    PubMed

    Bottagisio, Marta; Lovati, Arianna B; Lopa, Silvia; Moretti, Matteo

    2015-08-01

    Bone defects are severe burdens in clinics, and thus cell therapy offers an alternative strategy exploiting the features of bone marrow stromal cells (BMSCs). Sheep are a suitable orthopedic preclinical model for similarities with humans. This study compares the influence of two phosphate sources combined with bone morphogenetic protein-2 (BMP-2) on the osteogenic potential of human and ovine BMSCs. β-Glycerophosphate (β-GlyP) and monosodium phosphate (NaH2PO4) were used as organic and inorganic phosphate sources. Osteogenic differentiation of the BMSCs was assessed by calcified matrix, alkaline phosphatase (ALP) activity, and gene expression analysis. A higher calcified matrix deposition was detected in BMSCs cultured with NaH2PO4. Although no significant differences were detected among media for human BMSCs, β-GlyP with or without BMP-2 determined a positive trend in ALP levels compared to NaH2PO4. In contrast, NaH2PO4 had a positive effect on ALP levels in ovine BMSCs. β-GlyP better supported the expression of COL1A1 in human BMSCs, whereas all media enhanced RUNX2 and SPARC expression. Ovine BMSCs responded poorly to any media for RUNX2, COL1A1, and SPARC expression. NaH2PO4 improved calcified matrix deposition without upregulating the transcriptional expression of osteogenic markers. A further optimization of differentiation protocols needs to be performed to translate the procedures from preclinical to clinical models.

  15. Genetic disruption of the pHi-regulating proteins Na+/H+ exchanger 1 (SLC9A1) and carbonic anhydrase 9 severely reduces growth of colon cancer cells.

    PubMed

    Parks, Scott K; Cormerais, Yann; Durivault, Jerome; Pouyssegur, Jacques

    2017-02-07

    Hypoxia and extracellular acidosis are pathophysiological hallmarks of aggressive solid tumors. Regulation of intracellular pH (pHi) is essential for the maintenance of tumor cell metabolism and proliferation in this microenvironment and key proteins involved in pHi regulation are of interest for therapeutic development. Carbonic anhydrase 9 (CA9) is one of the most robustly regulated proteins by the hypoxia inducible factor (HIF) and contributes to pHi regulation. Here, we have investigated for the first time, the role of CA9 via complete genomic knockout (ko) and compared its impact on tumor cell physiology with the essential pHi regulator Na+/H+ exchanger 1 (NHE1). Initially, we established NHE1-ko LS174 cells with inducible CA9 knockdown. While increased sensitivity to acidosis for cell survival in 2-dimensions was not observed, clonogenic proliferation and 3-dimensional spheroid growth in particular were greatly reduced. To avoid potential confounding variables with use of tetracycline-inducible CA9 knockdown, we established CA9-ko and NHE1/CA9-dko cells. NHE1-ko abolished recovery from NH4Cl pre-pulse cellular acid loading while both NHE1 and CA9 knockout reduced resting pHi. NHE1-ko significantly reduced tumor cell proliferation both in normoxia and hypoxia while CA9-ko dramatically reduced growth in hypoxic conditions. Tumor xenografts revealed substantial reductions in tumor growth for both NHE1-ko and CA9-ko. A notable induction of CA12 occurred in NHE1/CA9-dko tumors indicating a potential means to compensate for loss of pH regulating proteins to maintain growth. Overall, these genomic knockout results strengthen the pursuit of targeting tumor cell pH regulation as an effective anti-cancer strategy.

  16. Genetic disruption of the pHi-regulating proteins Na+/H+ exchanger 1 (SLC9A1) and carbonic anhydrase 9 severely reduces growth of colon cancer cells

    PubMed Central

    Parks, Scott K.; Cormerais, Yann; Durivault, Jerome; Pouyssegur, Jacques

    2017-01-01

    Hypoxia and extracellular acidosis are pathophysiological hallmarks of aggressive solid tumors. Regulation of intracellular pH (pHi) is essential for the maintenance of tumor cell metabolism and proliferation in this microenvironment and key proteins involved in pHi regulation are of interest for therapeutic development. Carbonic anhydrase 9 (CA9) is one of the most robustly regulated proteins by the hypoxia inducible factor (HIF) and contributes to pHi regulation. Here, we have investigated for the first time, the role of CA9 via complete genomic knockout (ko) and compared its impact on tumor cell physiology with the essential pHi regulator Na+/H+ exchanger 1 (NHE1). Initially, we established NHE1-ko LS174 cells with inducible CA9 knockdown. While increased sensitivity to acidosis for cell survival in 2-dimensions was not observed, clonogenic proliferation and 3-dimensional spheroid growth in particular were greatly reduced. To avoid potential confounding variables with use of tetracycline-inducible CA9 knockdown, we established CA9-ko and NHE1/CA9-dko cells. NHE1-ko abolished recovery from NH4Cl pre-pulse cellular acid loading while both NHE1 and CA9 knockout reduced resting pHi. NHE1-ko significantly reduced tumor cell proliferation both in normoxia and hypoxia while CA9-ko dramatically reduced growth in hypoxic conditions. Tumor xenografts revealed substantial reductions in tumor growth for both NHE1-ko and CA9-ko. A notable induction of CA12 occurred in NHE1/CA9-dko tumors indicating a potential means to compensate for loss of pH regulating proteins to maintain growth. Overall, these genomic knockout results strengthen the pursuit of targeting tumor cell pH regulation as an effective anti-cancer strategy. PMID:28055960

  17. Close Association of Carbonic Anhydrase (CA2a and CA15a), Na+/H+ Exchanger (Nhe3b), and Ammonia Transporter Rhcg1 in Zebrafish Ionocytes Responsible for Na+ Uptake

    PubMed Central

    Ito, Yusuke; Kobayashi, Sayako; Nakamura, Nobuhiro; Miyagi, Hisako; Esaki, Masahiro; Hoshijima, Kazuyuki; Hirose, Shigehisa

    2013-01-01

    Freshwater (FW) fishes actively absorb salt from their environment to tolerate low salinities. We previously reported that vacuolar-type H+-ATPase/mitochondrion-rich cells (H-MRCs) on the skin epithelium of zebrafish larvae (Danio rerio) are primary sites for Na+ uptake. In this study, in an attempt to clarify the mechanism for the Na+ uptake, we performed a systematic analysis of gene expression patterns of zebrafish carbonic anhydrase (CA) isoforms and found that, of 12 CA isoforms, CA2a and CA15a are highly expressed in H-MRCs at larval stages. The ca2a and ca15a mRNA expression were salinity-dependent; they were upregulated in 0.03 mM Na+ water whereas ca15a but not ca2a was down-regulated in 70 mM Na+ water. Immunohistochemistry demonstrated cytoplasmic distribution of CA2a and apical membrane localization of CA15a. Furthermore, cell surface immunofluorescence staining revealed external surface localization of CA15a. Depletion of either CA2a or CA15a expression by Morpholino antisense oligonucleotides resulted in a significant decrease in Na+ accumulation in H-MRCs. An in situ proximity ligation assay demonstrated a very close association of CA2a, CA15a, Na+/H+ exchanger 3b (Nhe3b), and Rhcg1 ammonia transporter in H-MRC. Our findings suggest that CA2a, CA15a, and Rhcg1 play a key role in Na+uptake under FW conditions by forming a transport metabolon with Nhe3b. PMID:23565095

  18. Loss of PDZ-adaptor protein NHERF2 affects membrane localization and cGMP- and [Ca2+]- but not cAMP-dependent regulation of Na+/H+ exchanger 3 in murine intestine

    PubMed Central

    Chen, Mingmin; Sultan, Ayesha; Cinar, Ayhan; Yeruva, Sunil; Riederer, Brigitte; Singh, Anurag Kumar; Li, Junhua; Bonhagen, Janina; Chen, Gang; Yun, Chris; Donowitz, Mark; Hogema, Boris; deJonge, Hugo; Seidler, Ursula

    2010-01-01

    Trafficking and regulation of the epithelial brush border membrane (BBM) Na+/H+ exchanger 3 (NHE3) in the intestine involves interaction with four different members of the NHERF family in a signal-dependent and possibly segment-specific fashion. The aim of this research was to study the role of NHERF2 (E3KARP) in intestinal NHE3 BBM localization and second messenger-mediated and receptor-mediated inhibition of NHE3. Immunolocalization of NHE3 in WT mice revealed predominant microvillar localization in jejunum and colon, a mixed distribution in the proximal ileum but localization near the terminal web in the distal ileum. The terminal web localization of NHE3 in the distal ileum correlated with reduced acid-activated NHE3 activity (fluorometrically assessed). NHERF2 ablation resulted in a shift of NHE3 to the microvilli and higher basal fluid absorption rates in the ileum, but no change in overall NHE3 protein or mRNA expression. Forskolin-induced NHE3 inhibition was preserved in the absence of NHERF2, whereas Ca2+ ionophore- or carbachol-mediated inhibition was abolished. Likewise, Escherichia coli heat stable enterotoxin peptide (STp) lost its inhibitory effect on intestinal NHE3. It is concluded that in native murine intestine, the NHE3 adaptor protein NHERF2 plays important roles in tethering NHE3 to a position near the terminal web and in second messenger inhibition of NHE3 in a signal- and segment-specific fashion, and is therefore an important regulator of intestinal fluid transport. PMID:20962002

  19. Quantitative EEG and low resolution electromagnetic tomography (LORETA) imaging of patients with persistent auditory hallucinations.

    PubMed

    Lee, Seung-Hwan; Wynn, Jonathan K; Green, Michael F; Kim, Hyun; Lee, Kang-Joon; Nam, Min; Park, Joong-Kyu; Chung, Young-Cho

    2006-04-01

    Electrophysiological studies have demonstrated gamma and beta frequency oscillations in response to auditory stimuli. The purpose of this study was to test whether auditory hallucinations (AH) in schizophrenia patients reflect abnormalities in gamma and beta frequency oscillations and to investigate source generators of these abnormalities. This theory was tested using quantitative electroencephalography (qEEG) and low-resolution electromagnetic tomography (LORETA) source imaging. Twenty-five schizophrenia patients with treatment refractory AH, lasting for at least 2 years, and 23 schizophrenia patients with non-AH (N-AH) in the past 2 years were recruited for the study. Spectral analysis of the qEEG and source imaging of frequency bands of artifact-free 30 s epochs were examined during rest. AH patients showed significantly increased beta 1 and beta 2 frequency amplitude compared with N-AH patients. Gamma and beta (2 and 3) frequencies were significantly correlated in AH but not in N-AH patients. Source imaging revealed significantly increased beta (1 and 2) activity in the left inferior parietal lobule and the left medial frontal gyrus in AH versus N-AH patients. These results imply that AH is reflecting increased beta frequency oscillations with neural generators localized in speech-related areas.

  20. Enhancement of Population Size of a Biological Control Agent and Efficacy in Control of Bacterial Speck of Tomato through Salicylate and Ammonium Sulfate Amendments

    PubMed Central

    Ji, Pingsheng; Wilson, Mark

    2003-01-01

    Sodium salicylate and ammonium sulfate were applied to leaf surfaces along with suspensions of the biological control agents Pseudomonas syringae Cit7(pNAH7), which catabolizes salicylate, and Cit7, which does not catabolize salicylate, to determine whether enhanced biological control of bacterial speck of tomato could be achieved. Foliar amendment with salicylate alone significantly enhanced the population size and the efficacy of Cit7(pNAH7), but not of Cit7, on tomato leaves. Application of ammonium sulfate alone did not result in enhanced population size or biological control efficacy of either Cit7(pNAH7) or Cit7; however, when foliar amendments with both sodium salicylate and ammonium sulfate were applied, a trend toward further increases in population size and biological control efficacy of Cit7(pNAH7) was observed. This study demonstrates the potential of using a selective carbon source to improve the efficacy of a bacterial biological control agent in the control of a bacterial plant disease and supports previous conclusions that the growth of P. syringae in the phyllosphere is primarily carbon limited and secondarily nitrogen limited. PMID:12571060

  1. Perfusion of isolated carotid sinus with hydrogen sulfide attenuated the renal sympathetic nerve activity in anesthetized male rats.

    PubMed

    Guo, Q; Wu, Y; Xue, H; Xiao, L; Jin, S; Wang, R

    2016-07-18

    The purpose of the present study was to define the indirect central effect of hydrogen sulfide (H(2)S) on baroreflex control of sympathetic outflow. Perfusing the isolated carotid sinus with sodium hydrosulfide (NaHS), a H(2)S donor, the effect of H(2)S was measured by recording changes of renal sympathetic nerve activity (RSNA) in anesthetized male rats. Perfusion of isolated carotid sinus with NaHS (25, 50, 100 micromol/l) dose and time-dependently inhibited sympathetic outflow. Preconditioning of glibenclamide (20 micromol/l), a ATP-sensitive K(+) channels (K(ATP)) blocker, the above effect of NaHS was removed. With 1, 4-dihydro-2, 6-dimethyl-5-nitro-4-(2-[trifluoromethyl] phenyl) pyridine-3-carboxylic acid methyl ester (Bay K8644, 500 nmol/l) pretreatment, which is an agonist of L-calcium channels, the effect of NaHS was eliminated. Perfusion of cystathionine gamma-lyase (CSE) inhibitor, DL-propargylglycine (PPG, 200 micromol/l), increased sympathetic outflow. The results show that exogenous H(2)S in the carotid sinus inhibits sympathetic outflow. The effect of H(2)S is attributed to opening K(ATP) channels and closing the L-calcium channels.

  2. Quantenwelt im Nanozylinder: Elektronische Eigenschaften von Kohlenstoff-Nanoröhrchen

    NASA Astrophysics Data System (ADS)

    Strunk, Christoph

    2005-07-01

    Kohlenstoff-Nanoröhren sind einzelne oder mehrfach ineinander gesteckte molekulare Hohlzylinder. In ihnen bilden Kohlenstoffatome ein Graphit ähnliches Kristallgitter. Diese Fullerene zeichnen sich durch eine außerordentlich hohe Elastizität und Zugfestigkeit aus. In ihren elektronischen Eigenschaften verhalten sie sich entweder wie Halbleiter oder wie metallische Leiter. Aus halbleitenden Nanoröhren konnten bereits winzige Feldeffekttransistoren hergestellt werden, ein erster Schritt hin zu einer molekularen Elektronik. Die Grundlagenforscher interessiert vor allem das Verhalten metallischer Nanoröhren bei tiefen Temperaturen. An ihren elektronischen Systemen lassen sich zum Beispiel Quanteninterferenzphänomene oder Elektron-Elektron-Wechselwirkungen untersuchen.

  3. Alleviation of Drought Stress by Hydrogen Sulfide Is Partially Related to the Abscisic Acid Signaling Pathway in Wheat.

    PubMed

    Ma, Dongyun; Ding, Huina; Wang, Chenyang; Qin, Haixia; Han, Qiaoxia; Hou, Junfeng; Lu, Hongfang; Xie, Yingxin; Guo, Tiancai

    2016-01-01

    Little information is available describing the effects of exogenous H2S on the ABA pathway in the acquisition of drought tolerance in wheat. In this study, we investigated the physiological parameters, the transcription levels of several genes involved in the abscisic acid (ABA) metabolism pathway, and the ABA and H2S contents in wheat leaves and roots under drought stress in response to exogenous NaHS treatment. The results showed that pretreatment with NaHS significantly increased plant height and the leaf relative water content of seedlings under drought stress. Compared with drought stress treatment alone, H2S application increased antioxidant enzyme activities and reduced MDA and H2O2 contents in both leaves and roots. NaHS pretreatment increased the expression levels of ABA biosynthesis and ABA reactivation genes in leaves; whereas the expression levels of ABA biosynthesis and ABA catabolism genes were up-regulated in roots. These results indicated that ABA participates in drought tolerance induced by exogenous H2S, and that the responses in leaves and roots are different. The transcription levels of genes encoding ABA receptors were up-regulated in response to NaHS pretreatment under drought conditions in both leaves and roots. Correspondingly, the H2S contents in leaves and roots were increased by NaHS pretreatment, while the ABA contents of leaves and roots decreased. This implied that there is complex crosstalk between these two signal molecules, and that the alleviation of drought stress by H2S, at least in part, involves the ABA signaling pathway.

  4. Plant Hormone Salicylic Acid Produced by a Malaria Parasite Controls Host Immunity and Cerebral Malaria Outcome.

    PubMed

    Matsubara, Ryuma; Aonuma, Hiroka; Kojima, Mikiko; Tahara, Michiru; Andrabi, Syed Bilal Ahmad; Sakakibara, Hitoshi; Nagamune, Kisaburo

    2015-01-01

    The apicomplexan parasite Toxoplasma gondii produces the plant hormone abscisic acid, but it is unclear if phytohormones are produced by the malaria parasite Plasmodium spp., the most important parasite of this phylum. Here, we report detection of salicylic acid, an immune-related phytohormone of land plants, in P. berghei ANKA and T. gondii cell lysates. However, addition of salicylic acid to P. falciparum and T. gondii culture had no effect. We transfected P. falciparum 3D7 with the nahG gene, which encodes a salicylic acid-degrading enzyme isolated from plant-infecting Pseudomonas sp., and established a salicylic acid-deficient mutant. The mutant had a significantly decreased concentration of parasite-synthesized prostaglandin E2, which potentially modulates host immunity as an adaptive evolution of Plasmodium spp. To investigate the function of salicylic acid and prostaglandin E2 on host immunity, we established P. berghei ANKA mutants expressing nahG. C57BL/6 mice infected with nahG transfectants developed enhanced cerebral malaria, as assessed by Evans blue leakage and brain histological observation. The nahG-transfectant also significantly increased the mortality rate of mice. Prostaglandin E2 reduced the brain symptoms by induction of T helper-2 cytokines. As expected, T helper-1 cytokines including interferon-γ and interleukin-2 were significantly elevated by infection with the nahG transfectant. Thus, salicylic acid of Plasmodium spp. may be a new pathogenic factor of this threatening parasite and may modulate immune function via parasite-produced prostaglandin E2.

  5. Growth hormone in combination with leuprorelin in pubertal children with idiopathic short stature

    PubMed Central

    Benabbad, Imane; Rosilio, Myriam; Tauber, Maité; Paris, Emmanuel; Paulsen, Anne; Berggren, Lovisa; Patel, Hiren; Carel, Jean-Claude

    2018-01-01

    Objective There is a scarcity of data from randomised controlled trials on the association of growth hormone (GH) with gonadotrophin-releasing hormone agonists in idiopathic short stature (ISS), although this off-label use is common. We aimed to test whether delaying pubertal progression could increase near-adult height (NAH) in GH-treated patients with ISS. Methods Patients with ISS at puberty onset were randomised to GH with leuprorelin (combination, n = 46) or GH alone (n = 45). NAH standard deviation score (SDS) was the primary outcome measure. The French regulatory authority requested premature discontinuation of study treatments after approximately 2.4 years; patients from France were followed for safety. Results Mean (s.d.) baseline height SDS was −2.5 (0.5) in both groups, increasing at 2 years to −2.3 (0.6) with combination and −1.8 (0.7) with GH alone. NAH SDS was −1.8 (0.5) with combination (n = 19) and −1.9 (0.8) with GH alone (n = 16). Treatment-emergent adverse events and bone fractures occurred more frequently with combination than GH alone. Conclusion Due to premature discontinuation of treatments, statistical comparison of NAH SDS between the two cohorts was not possible. During the first 2–3 years of treatment, patients treated with the combination grew more slowly than those receiving GH alone. However, mean NAH SDS was similar in the two groups. No new GH-related safety concerns were revealed. A potentially deleterious effect of combined treatment on bone fracture incidence was identified. PMID:29669803

  6. Alleviation of Drought Stress by Hydrogen Sulfide Is Partially Related to the Abscisic Acid Signaling Pathway in Wheat

    PubMed Central

    Wang, Chenyang; Qin, Haixia; Han, Qiaoxia; Hou, Junfeng; Lu, Hongfang; Xie, Yingxin; Guo, Tiancai

    2016-01-01

    Little information is available describing the effects of exogenous H2S on the ABA pathway in the acquisition of drought tolerance in wheat. In this study, we investigated the physiological parameters, the transcription levels of several genes involved in the abscisic acid (ABA) metabolism pathway, and the ABA and H2S contents in wheat leaves and roots under drought stress in response to exogenous NaHS treatment. The results showed that pretreatment with NaHS significantly increased plant height and the leaf relative water content of seedlings under drought stress. Compared with drought stress treatment alone, H2S application increased antioxidant enzyme activities and reduced MDA and H2O2 contents in both leaves and roots. NaHS pretreatment increased the expression levels of ABA biosynthesis and ABA reactivation genes in leaves; whereas the expression levels of ABA biosynthesis and ABA catabolism genes were up-regulated in roots. These results indicated that ABA participates in drought tolerance induced by exogenous H2S, and that the responses in leaves and roots are different. The transcription levels of genes encoding ABA receptors were up-regulated in response to NaHS pretreatment under drought conditions in both leaves and roots. Correspondingly, the H2S contents in leaves and roots were increased by NaHS pretreatment, while the ABA contents of leaves and roots decreased. This implied that there is complex crosstalk between these two signal molecules, and that the alleviation of drought stress by H2S, at least in part, involves the ABA signaling pathway. PMID:27649534

  7. Plant Hormone Salicylic Acid Produced by a Malaria Parasite Controls Host Immunity and Cerebral Malaria Outcome

    PubMed Central

    Matsubara, Ryuma; Aonuma, Hiroka; Kojima, Mikiko; Tahara, Michiru; Andrabi, Syed Bilal Ahmad; Sakakibara, Hitoshi; Nagamune, Kisaburo

    2015-01-01

    The apicomplexan parasite Toxoplasma gondii produces the plant hormone abscisic acid, but it is unclear if phytohormones are produced by the malaria parasite Plasmodium spp., the most important parasite of this phylum. Here, we report detection of salicylic acid, an immune-related phytohormone of land plants, in P. berghei ANKA and T. gondii cell lysates. However, addition of salicylic acid to P. falciparum and T. gondii culture had no effect. We transfected P. falciparum 3D7 with the nahG gene, which encodes a salicylic acid-degrading enzyme isolated from plant-infecting Pseudomonas sp., and established a salicylic acid-deficient mutant. The mutant had a significantly decreased concentration of parasite-synthesized prostaglandin E2, which potentially modulates host immunity as an adaptive evolution of Plasmodium spp. To investigate the function of salicylic acid and prostaglandin E2 on host immunity, we established P. berghei ANKA mutants expressing nahG. C57BL/6 mice infected with nahG transfectants developed enhanced cerebral malaria, as assessed by Evans blue leakage and brain histological observation. The nahG-transfectant also significantly increased the mortality rate of mice. Prostaglandin E2 reduced the brain symptoms by induction of T helper-2 cytokines. As expected, T helper-1 cytokines including interferon-γ and interleukin-2 were significantly elevated by infection with the nahG transfectant. Thus, salicylic acid of Plasmodium spp. may be a new pathogenic factor of this threatening parasite and may modulate immune function via parasite-produced prostaglandin E2. PMID:26466097

  8. Verbindungsprogrammierte Steuerung

    NASA Astrophysics Data System (ADS)

    Linke, Petra

    Verbindungsprogrammierte Steuerungen werden eingesetzt, wenn die Anzahl der Verknüpfungsfunktionen gering ist oder spezifische Funktionen es erfordern. Nachteilig gegenüber Speicherprogrammierbaren Steuerungen sind die geringere Flexibilität, ein geringerer Funktionsumfang und die Tatsache, dass sich analoge oder digitale Daten praktisch nicht verarbeiten lassen.

  9. Increasing Pragmatic Awareness: Die Vagheit der Sprache "und so"

    ERIC Educational Resources Information Center

    Overstreet, Maryann; Tran, Jennie; Zietze, Sylvia

    2006-01-01

    This article presents a description of some pragmatic expressions ("oder so," "und so," "oder wie") rarely found in textbooks, but common in everyday conversation. Though often treated as vague or superfluous, these expressions perform important functions in interpersonal communication. Focusing on these easily identifiable phrases can help…

  10. Hydrogen sulfide alleviates toxic effects of arsenate in pea seedlings through up-regulation of the ascorbate-glutathione cycle: Possible involvement of nitric oxide.

    PubMed

    Singh, Vijay Pratap; Singh, Samiksha; Kumar, Jitendra; Prasad, Sheo Mohan

    2015-06-01

    In plants, hydrogen sulfide (H2S) is an emerging novel signaling molecule that is involved in growth regulation and abiotic stress responses. However, little is known about its role in the regulation of arsenate (As(V)) toxicity. Therefore, hydroponic experiments were conducted to investigate whether sodium hydrosulfide (NaHS; a source of H2S) is involved in the regulation of As(V) toxicity in pea seedlings. Results showed that As(V) caused decreases in growth, photosynthesis (measured as chlorophyll fluorescence) and nitrogen content, which was accompanied by the accumulation of As. As(V) treatment also reduced the activities of cysteine desulfhydrase and nitrate reductase, and contents of H2S and nitric oxide (NO). However, addition of NaHS ameliorated As(V) toxicity in pea seedlings, which coincided with the increased contents of H2S and NO. The cysteine level was higher under As(V) treatment in comparison to all other treatments (As-free; NaHS; As(V)+NaHS). The content of reactive oxygen species (ROS) and damage to lipids, proteins and membranes increased by As(V) while NaHS alleviated these effects. Enzymes of the ascorbate-glutathione cycle (AsA-GSH cycle) showed inhibition of their activities following As(V) treatment while their activities were increased by application of NaHS. The redox status of ascorbate and glutathione was disturbed by As(V) as indicated by a steep decline in their reduced/oxidized ratios. However, simultaneous NaHS application restored the redox status of the ascorbate and glutathione pools. The results of this study demonstrated that H2S and NO might both be involved in reducing the accumulation of As and triggering up-regulation of the AsA-GSH cycle to counterbalance ROS-mediated damage to macromolecules. Furthermore, the results suggest a crucial role of H2S in plant priming, and in particular for pea seedlings in mitigating As(V) stress. Copyright © 2015 Elsevier GmbH. All rights reserved.

  11. Effect of hydrogen sulfide on inflammatory cytokines in acute myocardial ischemia injury in rats

    PubMed Central

    LIU, FANG; LIU, GUANG-JIE; LIU, NA; ZHANG, GANG; ZHANG, JIAN-XIN; LI, LAN-FANG

    2015-01-01

    Hydrogen sulfide (H2S) is believed to be involved in numerous physiological and pathophysiological processes, and now it is recognized as the third endogenous signaling gasotransmitter, following nitric oxide and carbon monoxide; however, the effects of H2S on inflammatory factors in acute myocardial ischemia injury in rats have not been clarified. In the present study, sodium hydrosulfide (NaHS) was used as the H2S donor. Thirty-six male Sprague Dawley rats were randomly divided into five groups: Sham, ischemia, ischemia + low-dose (0.78 mg/kg) NaHS, ischemia + medium-dose (1.56 mg/kg) NaHS, ischemia + high-dose (3.12 mg/kg) NaHS and ischemia + propargylglycine (PPG) (30 mg/kg). The rats in each group were sacrificed 6 h after the surgery for sample collection. Compared with the ischemia group, the cardiac damage in the rats in the ischemia + NaHS groups was significantly reduced, particularly in the high-dose group; in the ischemia + PPG group, the myocardial injury was aggravated compared with that in the ischemia group. Compared with the ischemia group, the levels of interleukin (IL)-1β, IL-6 and tumor necrosis factor-α (TNF-α) in the serum of rats in the ischemia + medium- and high-dose NaHS groups were significantly reduced, and the expression of intercellular adhesion molecule-1 (ICAM-1) mRNA and nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) protein in the myocardial tissues of rats was significantly reduced. In the ischemia + PPG group, the TNF-α, IL-1β and IL-6 levels in the serum were significantly increased, the expression of ICAM-1 mRNA was increased, although without a significant difference, and the expression of NF-κB was increased. The findings of the present study provide novel evidence for the dual effects of H2S on acute myocardial ischemia injury via the modulation of inflammatory factors. PMID:25667680

  12. H2S improves renal fibrosis in STZ-induced diabetic rats by ameliorating TGF-β1 expression.

    PubMed

    Li, Yan; Li, Lin; Zeng, Ou; Liu, Jun Mao; Yang, Jun

    2017-11-01

    Nephropathy develops in many patients with type 1 diabetes mellitus (T1DM). However, the specific mechanisms and therapies remain unclear. For this purpose we investigated the effects of hydrogen sulfide (H 2 S) on renal fibrosis in streptozotocin (STZ) induced diabetic rats and its underlying mechanisms. Experimental rats were randomly divided into four groups: Control group (normal rats), DM group (diabetes rats), DM + NaHS group [diabetes rats treated with sodium hydrosulfide (NaHS)], and NaHS group (normal rats treated with NaHS). The diabetic models were established by intraperitoneal injection of STZ. The NaHS-treated rats were injected with NaHS as an exogenous donor of H 2 S. At the same time, control group and DM group were administrated with equal doses of normal saline (NS). After eight weeks, the rats' urine samples were collected to measure the renal hydroxyproline content by basic hydrolysis method with a hydroxyproline detection kit. Collagen I and III content was detected by immunohistochemical method, and the pathology morphology of kidney was analyzed by Masson staining. Protein expressions of transforming growth factor beta 1 (TGF-β1), ERK1/2, TIMP1, TIMP2, MMP-2, MMP-7, MMP-8, MMP-11, and MMP-14 were assessed by western blotting. The results showed that significant fibrosis occurred in the kidney of diabetes rats. NaHS treatment downregulated TGF-β1, ERK1/2, TIMP1, TIMP2, MMP-2, MMP-7, MMP-8, MMP-11, and MMP-14 expressions in the kidney of these diabetes rats (p<.01). This result suggests that NaHS treatment could attenuate renal fibrosis by TGF-β1 signaling, and its mechanisms may be correlated with ERK1/2 expression and modulation of MMPs/TIMPs expression. Therefore, H 2 S may provide a promising option for defensing against diabetic renal fibrosis through TGF-β1 signaling, equilibrating the balance between profibrotic and antifibrotic mediators.

  13. Increased height standard deviation scores in response to growth hormone therapy to near-adult height in older children with delayed skeletal maturation: results from the ANSWER Program.

    PubMed

    Ross, Judith L; Lee, Peter A; Gut, Robert; Germak, John

    2015-01-01

    A primary goal of recombinant human growth hormone therapy (GHT) in children is attaining normal adult height. In this study, children with growth hormone deficiency (GHD) (including isolated idiopathic growth hormone deficiency [IGHD] and multiple pituitary hormone deficiency [MPHD]), idiopathic short stature (ISS), and Turner syndrome (TS) were evaluated for near-adult height (NAH) and percent achieving NAH within the normal range after approximately 4 years of GHT. Data from the American Norditropin® Web-Enabled Research (ANSWER) Program were analyzed for NAH from age at treatment start (ATS) (i.e., referral age as defined by age at enrollment in the study) to last clinic visit using one of the following two criteria: 1) age ≥18 years, or 2) if male: ≥16 years and height velocity (HV) <2 cm/year; if female: ≥15 years and HV <2 cm/year. All patients had a baseline height standard deviation score (HSDS) ≤ -2, and either GHD (n = 201), ISS (n = 19), or TS (n = 41). The main outcome measures included HSDS and corrected HSDS (HSDS-target HSDS) in response to GH treatment, and correlation of ATS with NAH HSDS. Mean (± SD) chronological and bone ages at baseline were 14.0 ± 2.1 years and 11.7 ± 2.0 years, respectively, and mean GHT duration was 4.0 ± 1.6 years. Mean HSDS (baseline to NAH; GHD: -2.7 to -1.0; ISS: -2.8 to -1.4; TS: -3.0 to -1.8) and mean corrected HSDS (baseline to NAH; GHD: -2.1 to -0.3; ISS: -2.1 to -0.6; TS: -1.8 to -0.6) increased across diagnostic indications. Percentages of patients reaching near-adult HSDS > -2 were GHD: 87.6%; ISS: 78.9%; TS: 65.8%. Significant negative correlations were found between ATS and NAH HSDS when analyzed by sex. Despite a relatively advanced childhood age, the majority of GH-treated patients attained mean near-adult HSDS within the normal range (HSDS > -2). Negative correlations of ATS with near-adult HSDS indicate that an earlier age at treatment start would

  14. Kunststoffe (Polymere)

    NASA Astrophysics Data System (ADS)

    Weißbach, Wolfgang

    Polymere bestehen aus Riesen- oder Makromolekülen, die durch chemische Reaktionen aus einfachen, niedermolekularen Verbindungen entstehen, den Monomeren. Ausgangsstoffe sind überwiegend Kohlenwasserstoffe (KW), die größte Gruppe der C-Verbindungen. Sie müssen reaktionsfähige Stellen besitzen, das sind OH-Gruppen oder Dopppelbindungen.

  15. Implantate im Mittelohrbereich - Teil 2 (Ergänzungen 2007)

    NASA Astrophysics Data System (ADS)

    Stieve, M.; Lenarz, Thomas

    In Deutschland leben ca. 12 Millionen Menschen, die an einer ein- oder beidseitigen Schwerhörigkeit leiden. Diese kann angeboren oder im Laufe des Lebens erworben sein. Klinisch und therapeutisch wichtig ist die Unterscheidung hinsichtlich des Schädigungsortes im Bereich des Mittelohres, d. h. eine Schalleitungsschwerhörigkeit, oder im Bereich des Innenohres, d. h. eine Schallempfindungsschwerhörigkeit, wobei hier der Schädigungsort auch am Hörnerven oder in den zentralen Hörabschnitten liegen kann. Therapeutisch lassen sich sowohl Schwerhörigkeiten im Bereich des Mittelohres als auch im Innenohr und sogar im Hirnstammbereich (Hirnstammimplantat) behandeln. 1,9 Millionen Schwerhörige haben eine Erkrankung im Mittelohrbereich, d. h. der Schall kann nur ungenügend auf das Innenohr übertragen werden. Die Ursache besteht meist in einer chronischen Mittelohrentzündung, die zu einer Zerstörung des Trommelfells und der Gehörknöchelchenkette geführt haben. Therapeutisch und damit als Prinzip der operativen Hörverbesserung steht primär der Verschluß des Trommelfells oder eine Rekonstruktion der Gehörknöchelchen. Mittelohroperationen werden mikrochirurgisch unter dem Operationsmikroskop durchgeführt, wobei zunächst durch eine sanierende Operation der Entzündungsprozeß entfernt wird und nach einer Ausheilungszeit die Gehörknöchelchenkette durch künstliche Prothesen rekonstruiert werden kann.

  16. Variations of body composition, physical activity and caloric intake in schoolchildren during national holidays.

    PubMed

    Cristi-Montero, Carlos; Munizaga, Cristian; Tejos, Constanza; Ayala, Raquel; Henríquez, Raúl; Solís-Urra, Patricio; Rodríguez-Rodríguez, Fernando

    2016-06-01

    Scientific literature has described that a significant body weight increase in schoolchildren occurs during some holiday periods (summer, winter, and thanksgiving holidays), harming their health. In this regard, it is thought that this phenomenon is mainly due to changes in eating habits and the variation in levels of physical activity; however, this approach has not yet been explored during national holidays (NAH) in Chile. To determine any changes in body composition, physical activity and caloric intake during NAH. A total of 46 schoolchildren (24 boys, age 10.5 ± 0.5; BMI 21.7 ± 4.7) participated. Measurements were performed 2 days before and after the NAH (9 days). Weight was measured and fat percentage was established using the Slaughter formula. Levels of physical activity were measured with accelerometers, validating 3 weekdays and 1 weekend; caloric intake was established through a 24-h recall. Weight, percentage of fat and caloric intake increased significantly (250 g, 2.2 % and 733.3 kcal, respectively; p < 0.05); however, none of the variables of physical activity showed significant changes. The change in caloric intake seems to be the main cause of weight and fat gain during the NAH.

  17. The Characterization of Military Aircraft Jet Noise Using Near-Field Acoustical Holography Methods

    NASA Astrophysics Data System (ADS)

    Wall, Alan Thomas

    The noise emissions of jets from full-scale engines installed on military aircraft pose a significant hearing loss risk to military personnel. Noise reduction technologies and the development of operational procedures that minimize noise exposure to personnel are enhanced by the accurate characterization of noise sources within a jet. Hence, more than six decades of research have gone into jet noise measurement and prediction. In the past decade, the noise-source visualization tool near-field acoustical holography (NAH) has been applied to jets. NAH fits a weighted set of expansion wave functions, typically planar, cylindrical, or spherical, to measured sound pressures in the field. NAH measurements were made of a jet from an installed engine on a military aircraft. In the present study, the algorithm of statistically optimized NAH (SONAH) is modified to account for the presence of acoustic reflections from the concrete surface over which the jet was measured. The three dimensional field in the jet vicinity is reconstructed, and information about sources is inferred from reconstructions at the boundary of the turbulent jet flow. Then, a partial field decomposition (PFD) is performed, which represents the total field as the superposition of multiple, independent partial fields. This is the most direct attempt to equate partial fields with independent sources in a jet to date.

  18. Complex conductivity response to microbial growth and biofilm formation on phenanthrene spiked medium

    NASA Astrophysics Data System (ADS)

    Albrecht, Remy; Gourry, Jean Christophe; Simonnot, Marie-Odile; Leyval, Corinne

    2011-11-01

    Several laboratory studies have recently demonstrated the utility of geophysical methods for the investigation of microbial-induced changes over contaminated sites. However, it remains difficult to distinguish the effects due to the new physical properties imparted by microbial processes, to bacterial growth, or to the development of bacterial biofilm. We chose to study the influence of biofilm formation on geophysical response using complex conductivity measurements (0.1-1000 Hz) in phenanthrene-contaminated media. Biotic assays were conducted with two phenanthrene (PHE) degrading bacterial strains: Burkholderia sp (NAH1), which produced biofilm and Stenophomonas maltophilia (MATE10), which did not, and an abiotic control. Results showed that bacterial densities for NAH1 and MATE10 strains continuously increased at the same rate during the experiment. However, the complex conductivity signature showed noticeable differences between the two bacteria, with a phase shift of 50 mrad at 4 Hz for NAH1, which produced biofilm. Biofilm volume was quantified by Scanning Confocal Laser Microscopy (SCLM). Significant correlations were established between phase shift decrease and biofilm volume for NAH1 assays. Results suggest that complex conductivity measurements, specifically phase shift, can be a useful indicator of biofilm formation inside the overall signal of microbial activity on contaminated sites.

  19. Synthesis of sodium polyhydrides at high pressures

    DOE PAGES

    Struzhkin, Viktor V.; Kim, Duck Young; Stavrou, Elissaios; ...

    2016-07-28

    Archetypal ionic NaH is the only known compound of sodium and hydrogen. Application of high pressure is known to promote states with higher atomic coordination, but extensive searches for polyhydrides with unusual stoichiometry have had only limited success in spite of several theoretical predictions. Here we report the first observation of the formation of polyhydrides of Na (NaH 3 and NaH 7) above 40 GPa and 2,000 K. Moreover, we combine synchrotron X-ray diffraction and Raman spectroscopy in a laser-heated diamond anvil cell and theoretical random structure searching, which both agree on the stable structures and compositions. Our results supportmore » the formation of multicenter bonding in a material with unusual stoichiometry. These results are applicable to the design of new energetic solids and high-temperature superconductors based on hydrogen-rich materials.« less

  20. Synthesis of sodium polyhydrides at high pressures

    NASA Astrophysics Data System (ADS)

    Struzhkin, Viktor V.; Kim, Duck Young; Stavrou, Elissaios; Muramatsu, Takaki; Mao, Ho-Kwang; Pickard, Chris J.; Needs, Richard J.; Prakapenka, Vitali B.; Goncharov, Alexander F.

    2016-07-01

    The only known compound of sodium and hydrogen is archetypal ionic NaH. Application of high pressure is known to promote states with higher atomic coordination, but extensive searches for polyhydrides with unusual stoichiometry have had only limited success in spite of several theoretical predictions. Here we report the first observation of the formation of polyhydrides of Na (NaH3 and NaH7) above 40 GPa and 2,000 K. We combine synchrotron X-ray diffraction and Raman spectroscopy in a laser-heated diamond anvil cell and theoretical random structure searching, which both agree on the stable structures and compositions. Our results support the formation of multicenter bonding in a material with unusual stoichiometry. These results are applicable to the design of new energetic solids and high-temperature superconductors based on hydrogen-rich materials.

  1. Kommunikation mit Mitarbeitern

    NASA Astrophysics Data System (ADS)

    Spychala, Anne; Fleischmann, Jürgen

    Kommunikation ist der Austausch von Nachrichten und Informationen zwischen Mitarbeitern eines Unternehmens (O'Hair et al. 1997). Dieser Austausch kann persönlich, aber z.B. auch per Telefon, E-Mail oder durch Computersysteme erfolgen. In diesem Kapitel betrachten wir die persönliche Kommunikation zwischen Vorgesetzten und Mitarbeitern. Zur persönlichen Kommunikation mit Mitarbeitern zählen sowohl formelle Gespräche mit Mitarbeitern als auch eher informelle Gespräche zwischen Tür und Angel. Die Gespräche können dabei mit einzelnen Mitarbeitern (z.B. jährliches Mitarbeitergespräch) oder mit Gruppen von Mitarbeitern (z.B. regelmäßige Projekt- oder Teambesprechungen) stattfinden.

  2. High-mobility group box 1 inhibits HCO3− absorption in the medullary thick ascending limb through RAGE-Rho-ROCK-mediated inhibition of basolateral Na+/H+ exchange

    PubMed Central

    Watts, Bruns A.; George, Thampi; Badalamenti, Andrew

    2016-01-01

    High-mobility group box 1 (HMGB1) is a nuclear protein released extracellularly in response to infection or injury, where it activates immune responses and contributes to the pathogenesis of kidney dysfunction in sepsis and sterile inflammatory disorders. Recently, we demonstrated that HMGB1 inhibits HCO3− absorption in perfused rat medullary thick ascending limbs (MTAL) through a basolateral receptor for advanced glycation end products (RAGE)-dependent pathway that is additive to Toll-like receptor 4 (TLR4)-ERK-mediated inhibition by LPS (Good DW, George T, Watts BA III. Am J Physiol Renal Physiol 309: F720–F730, 2015). Here, we examined signaling and transport mechanisms that mediate inhibition by HMGB1. Inhibition of HCO3− absorption by HMGB1 was eliminated by the Rho-associated kinase (ROCK) inhibitor Y27632 and by a specific inhibitor of Rho, the major upstream activator of ROCK. HMGB1 increased RhoA and ROCK1 activity. HMGB1-induced ROCK1 activation was eliminated by the RAGE antagonist FPS-ZM1 and by inhibition of Rho. The Rho and ROCK inhibitors had no effect on inhibition of HCO3− absorption by bath LPS. Inhibition of HCO3− absorption by HMGB1 was eliminated by bath amiloride, 0 Na+ bath, and the F-actin stabilizer jasplakinolide, three conditions that selectively prevent inhibition of MTAL HCO3− absorption mediated through NHE1. HMGB1 decreased basolateral Na+/H+ exchange activity through activation of ROCK. We conclude that HMGB1 inhibits HCO3− absorption in the MTAL through a RAGE-RhoA-ROCK1 signaling pathway coupled to inhibition of NHE1. The HMGB1-RAGE-RhoA-ROCK1 pathway thus represents a potential target to attenuate MTAL dysfunction during sepsis and other inflammatory disorders. HMGB1 and LPS inhibit HCO3− absorption through different receptor signaling and transport mechanisms, which enables these pathogenic mediators to act directly and independently to impair MTAL function. PMID:27358052

  3. Strahlen-und kinetische Waffen: Neue Waffentechniken und Rüstungskontrolle

    NASA Astrophysics Data System (ADS)

    Neuneck, Götz

    Laserstrahlen, Mikrowellen oder elektromagnetische Beschleuniger lassen sich nicht nur für zivile, sondern für militärische Zwecke einsetzen. Die Aufgabe einer vorbeugenden Rüstungskontrolle wäre es, diese wie andere künftige Waffentechnologien auf ihren destabilisierenden Charakter hin zu untersuchen und ihre Stationierung zu beschränken oder zu verhindern.

  4. Aspartate Carbamyltransferase : Site of End-Product Inhibition of the Orotate Pathway in Intact Cells of Cucurbita pepo.

    PubMed

    Lovatt, C J; Cheng, A H

    1984-07-01

    Lovatt et al. (1979 Plant Physiol 64: 562-569) have previously demonstrated that end-product inhibition functions as a mechanism regulating the activity of the orotic acid pathway in intact cells of roots excised from 2-day-old squash plants (Cucurbita pepo L. cv Early Prolific Straightneck). Uridine (0.5 millimolar final concentration) or one of its metabolites inhibited the incorporation of NaH(14)CO(3), but not [(14)C]carbamylaspartate or [(14)C]orotic acid, into uridine nucleotides (SigmaUMP). Thus, regulation of de novo pyrimidine biosynthesis was demonstrated to occur at one or both of the first two reactions of the orotic acid pathway, those catalyzed by carbamylphosphate synthetase (CPSase) and aspartate carbamyltransferase (ACTase). The results of the present study provide evidence that ACTase alone is the site of feedback control by added uridine or one of its metabolites. Evidence demonstrating regulation of the orotic acid pathway by end-product inhibition at ACTase, but not at CPSase, includes the following observations: (a) addition of uridine (0.5 millimolar final concentration) inhibited the incorporation of NaH(14)CO(3) into SigmaUMP by 80% but did not inhibit the incorporation of NaH(14)CO(3) into arginine; (b) inhibition of the orotate pathway by added uridine was not reversed by supplying exogenous ornithine (5 millimolar final concentration), while the incorporation of NaH(14)CO(3) into arginine was stimulated more than 15-fold when both uridine and ornithine were added; (c) incorporation of NaH(14)CO(3) into arginine increased, with or without added ornithine when the de novo pyrimidine pathway was inhibited by added uridine; and (d) in assays employing cell-free extracts prepared from 2-day-old squash roots, the activity of ACTase, but not CPSase, was inhibited by added pyrimidine nucleotides.

  5. Hydrogen sulphide decreases IL-1β-induced activation of fibroblast-like synoviocytes from patients with osteoarthritis

    PubMed Central

    Sieghart, Daniela; Liszt, Melissa; Wanivenhaus, Axel; Bröll, Hans; Kiener, Hans; Klösch, Burkhard; Steiner, Günter

    2015-01-01

    Balneotherapy employing sulphurous thermal water is still applied to patients suffering from diseases of musculoskeletal system like osteoarthritis (OA) but evidence for its clinical effectiveness is scarce. Since the gasotransmitter hydrogen sulphide (H2S) seems to affect cells involved in degenerative joint diseases, it was the objective of this study to investigate the effects of exogenous H2S on fibroblast-like synoviocytes (FLS), which are key players in OA pathogenesis being capable of producing pro-inflammatory cytokines and matrix degrading enzymes. To address this issue primary FLS derived from OA patients were stimulated with IL-1β and treated with the H2S donor NaHS. Cellular responses were analysed by ELISA, quantitative real-time PCR, phospho-MAPkinase array and Western blotting. Treatment-induced effects on cellular structure and synovial architecture were investigated in three-dimensional extracellular matrix micromasses. NaHS treatment reduced both spontaneous and IL-1β-induced secretion of IL-6, IL-8 and RANTES in different experimental settings. In addition, NaHS treatment reduced the expression of matrix metallo-proteinases MMP-2 and MMP-14. IL-1β induced the phosphorylation of several MAPkinases. NaHS treatment partially reduced IL-1β-induced activation of several MAPK whereas it increased phosphorylation of pro-survival factor Akt1/2. When cultured in spherical micromasses, FLS intentionally established a synovial lining layer-like structure; stimulation with IL-1β altered the architecture of micromasses leading to hyperplasia of the lining layer which was completely inhibited by concomitant exposure to NaHS. These data suggest that H2S partially antagonizes IL-1β stimulation via selective manipulation of the MAPkinase and the PI3K/Akt pathways which may encourage development of novel drugs for treatment of OA. PMID:25312962

  6. Hydrogen sulfide regulates the levels of key metabolites and antioxidant defense system to counteract oxidative stress in pepper (Capsicum annuum L.) plants exposed to high zinc regime.

    PubMed

    Kaya, Cengiz; Ashraf, Muhammad; Akram, Nudrat Aisha

    2018-05-01

    In the present experiment, we aimed to test the impact of hydrogen sulfide (H 2 S) on growth, key oxidant such as hydrogen peroxide, mineral elements, and antioxidative defense in Capia-type red sweet pepper (Capsicum annuum L.) plants subjected to high concentration of zinc (Zn). A factorial experiment was designed with two Zn levels (0.05 and 0.5 mM) and 0.2 mM sodium hydrosulfide (NaHS) as a donor of H 2 S supplied in combination plus nutrient solution through the root zone. High level of Zn led to reduce dry mass, chlorophyll pigments, fruit yield, leaf maximum fluorescence, and relative water content, but enhanced endogenous hydrogen peroxide (H 2 O 2 ), free proline, malondialdehyde (MDA), electrolyte leakage (EL), H 2 S, as well as the activities of peroxidase (POD), catalase (CAT), and superoxide dismutase (SOD) enzymes. Exogenously applied NaHS significantly enhanced plant growth, fruit yield, water status, the levels of H 2 S and proline as well as the activities of different antioxidant enzymes, while it significantly suppressed EL, MDA, and H 2 O 2 contents in the pepper plants receiving low level Zn. NaHS application to the control plants did not significantly change all these parameters tested except the dry matter which increased significantly. High Zn regime led to increase intrinsic Zn levels in the leaves and roots, but it lowered leaf nitrogen (N), phosphorus (P), and iron (Fe) concentrations. However, NaHS reduces the Zn conc. and enhances Fe and N in leaf and root organs. It can be concluded that NaHS can mitigate the harmful effects of Zn on plant growth particularly by lowering the concentrations of H 2 O 2 , Zn, EL, and MDA, and enhancing the activities of enzymatic antioxidants and levels of essential nutrients in pepper plants.

  7. Hydrogen sulphide inhibits carbachol-induced contractile responses in β-escin permeabilized guinea-pig taenia caecum.

    PubMed

    Denizalti, Merve; Durlu-Kandilci, N Tugba; Bozkurt, T Emrah; Sahin-Erdemli, Inci

    2011-05-11

    Hydrogen sulphide (H(2)S) is an endogenous mediator producing a potent relaxation response in vascular and non-vascular smooth muscles. While ATP-sensitive potassium channels are mainly involved in this relaxant effect in vascular smooth muscle, the mechanism in other smooth muscles has not been revealed yet. In the present study, we investigated how H(2)S relaxes non-vascular smooth muscle by using intact and β-escin permeabilized guinea-pig taenia caecum. In intact tissues, concentration-dependent relaxation response to H(2)S donor NaHS in carbachol-precontracted preparations did not change in the presence of a K(ATP) channel blocker glibenclamide, adenylate cyclase inhibitor SQ-22536, guanylate cyclase inhibitor ODQ, protein kinase A inhibitor KT-5720, protein kinase C inhibitor H-7, tetrodotoxin, apamin/charybdotoxin, NOS inhibitor L-NAME and cyclooxygenase inhibitor indomethacin. We then studied how H(2)S affected carbachol- or Ca(2+)-induced contractions in permeabilized tissues. When Ca(2+) was clamped to a constant value (pCa6), a further contraction could be elicited by carbachol that was decreased by NaHS. This decrease in contraction was reversed by catalase but not by superoxide dismutase or N-acetyl cysteine. The sarcoplasmic reticulum Ca(2+)-ATPase pump inhibitor, cyclopiazonic acid, also decreased the carbachol-induced contraction that was further inhibited by NaHS. Mitochondrial proton pump inhibitor carbonyl cyanide p-trifluromethoxyphenylhydrazone also decreased the carbachol-induced contraction but this was not additionally changed by NaHS. The carbachol-induced Ca(2+) sensitization, calcium concentration-response curves, IP(3)- and caffeine-induced contractions were not affected by NaHS. In conclusion, we propose that hydrogen peroxide and mitochondria may have a role in H(2)S-induced relaxation response in taenia caecum. Copyright © 2011 Elsevier B.V. All rights reserved.

  8. Response of PAH-degrading genes to PAH bioavailability in the overlying water, suspended sediment, and deposited sediment of the Yangtze River.

    PubMed

    Xia, Xinghui; Xia, Na; Lai, Yunjia; Dong, Jianwei; Zhao, Pujun; Zhu, Baotong; Li, Zhihuang; Ye, Wan; Yuan, Yue; Huang, Junxiong

    2015-06-01

    The degrading genes of hydrophobic organic compounds (HOCs) serve as indicators of in situ HOC degradation potential, and the existing forms and bioavailability of HOCs might influence the distribution of HOC-degrading genes in natural waters. However, little research has been conducted to study the relationship between them. In the present study, nahAc and nidA genes, which act as biomarkers for naphthalene- and pyrene-degrading bacteria, were selected as model genotypes to investigate the response of polycyclic aromatic hydrocarbon (PAH)-degrading genes to PAH bioavailability in the overlying water, suspended sediment (SPS), and deposited sediment of the Yangtze River. The freely dissolved concentration, typically used to reflect HOC bioavailability, and total dissolved, as well as sorbed concentrations of PAHs were determined. Phylogenetic analysis showed that all the PAH-ring hydroxylating dioxygenase gene sequences of Gram-negative bacteria (PAH-RHD[GN]) were closely related to nahAc, nagAc, nidA, and uncultured PAH-RHD genes. The PAH-RHD[GN] gene diversity as well as nahAc and nidA gene copy numbers decreased in the following order: deposited sediment>SPS>overlying water. The nahAc and nidA gene abundance was not significantly correlated with environmental parameters but was significantly correlated with the bioavailable existing forms of naphthalene and pyrene in the three phases. The nahAc gene copy numbers in the overlying water and deposited sediment were positively correlated with freely dissolved naphthalene concentrations in the overlying and pore water phases, respectively, and so were nidA gene copy numbers. This study suggests that the distribution and abundance of HOC-degrading bacterial population depend on the HOC bioavailability in aquatic environments. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. H2S-induced HCO3- secretion in the rat stomach--involvement of nitric oxide, prostaglandins, and capsaicin-sensitive sensory neurons.

    PubMed

    Takeuchi, Koji; Ise, Fumitaka; Takahashi, Kento; Aihara, Eitaro; Hayashi, Shusaku

    2015-04-30

    Hydrogen sulfide (H2S) is known to be an important gaseous mediator that affects various functions under physiological and pathological conditions. We examined the effects of NaHS, a H2S donor, on HCO3(-) secretion in rat stomachs and investigated the mechanism involved in this response. Under urethane anesthesia, rat stomachs were mounted on an ex vivo chamber and perfused with saline. Acid secretion had been inhibited by omeprazole. The secretion of HCO3(-) was measured at pH 7.0 using a pH-stat method and by the addition of 10 mM HCl. NaHS (0.5-10 mM) was perfused in the stomach for 5 min. Indomethacin or L-NAME was administered s.c. before NaHS treatment, while glibenclamide (a KATP channel blocker), ONO-8711 (an EP1 antagonist), or propargylglycine (a cystathionine γ-lyase inhibitor) was given i.p. before. The mucosal perfusion of NaHS dose-dependently increased the secretion of HCO3(-), and this effect was significantly attenuated by indomethacin, L-NAME, and sensory deafferentation, but not by glibenclamide or ONO-8711. The luminal output of nitric oxide, but not the mucosal production of prostaglandin E2, was increased by the perfusion of NaHS. Mucosal acidification stimulated HCO3(-) secretion, and this response was inhibited by sensory deafferentation, indomethacin, L-NAME, and ONO-8711, but not by propargylglycine. These results suggested that H2S increased HCO3(-) secretion in the stomach, and this effect was mediated by capsaicin-sensitive afferent neurons and dependent on nitric oxide and prostaglandins, but not ATP-sensitive K(+) channels. Further study is needed to define the role of endogenous H2S in the mechanism underlying acid-induced gastric HCO3(-) secretion. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Role of silent information regulator 1 in the protective effect of hydrogen sulfide on homocysteine-induced cognitive dysfunction: Involving reduction of hippocampal ER stress.

    PubMed

    Tang, Yi-Yun; Wang, Ai-Ping; Wei, Hai-Jun; Li, Man-Hong; Zou, Wei; Li, Xiang; Wang, Chun-Yan; Zhang, Ping; Tang, Xiao-Qing

    2018-04-16

    Homocysteine (Hcy) causes cognitive deficits and hippocampal endoplasmic reticulum (ER) stress. Our previous study has confirmed that Hydrogen sulfide (H 2 S) attenuates Hcy-induced cognitive dysfunction and hippocampal ER stress. Silent information regulator 1 (Sirt-1) is indispensable in the formation of learning and memory. Therefore, the aim of this study was to explore the role of Sirt-1 in the protective effect of H 2 S against Hcy-induced cognitive dysfunction. We found that NaHS (a donor of H 2 S) markedly up-regulated the expression of Sirt-1 in the hippocampus of Hcy-exposed rats. Sirtinol, a specific inhibitor of Sirt-1, reversed the improving role of NaHS in the cognitive function of Hcy-exposed rats, as evidenced by that sirtinol increased the escape latency and the swim distance in the acquisition trial of morris water maze (MWM) test, decreased the times crossed through and the time spent in the target quadrant in the probe trail of MWM test, and reduced the discrimination index in the novel object recognition test (NORT) in the rats cotreated with NaHS and Hcy. We also found that sirtinol reversed the protection of NaHS against Hcy-induced hippocampal ER-stress, as evidenced by up-regulating the expressions of GRP78, CHOP, and cleaved caspase-12 in the hippocampus of rats cotreated with NaHS and Hcy. These results suggested the contribution of upregulation of hippocampal Sirt-1 to the improving role of H 2 S in the cognitive function of Hcy-exposed rats, which involves suppression of hippocampal ER stress. Our finding provides a new insight into the mechanism underlying the inhibitory role of H 2 S in Hcy-induced cognitive dysfunction. Copyright © 2018 Elsevier B.V. All rights reserved.

  11. H{sub 2}S induces vasoconstriction of rat cerebral arteries via cAMP/adenylyl cyclase pathway

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Li, Sen; Ping, Na-na; Cao, Lei, E-mail: leicao@mail.xjtu.edu.cn

    2015-12-15

    Hydrogen sulfide (H{sub 2}S), traditionally known for its toxic effects, is now involved in regulating vascular tone. Here we investigated the vasoconstrictive effect of H{sub 2}S on cerebral artery and the underlying mechanism. Sodium hydrosulfide (NaHS), a donor of H{sub 2}S, concentration-dependently induced vasoconstriction on basilar artery, which was enhanced in the presence of isoprenaline, a β-adrenoceptor agonist or forskolin, an adenylyl cyclase activator. Administration of NaHS attenuated the vasorelaxant effects of isoprenaline or forskolin. Meanwhile, the NaHS-induced vasoconstriction was diminished in the presence of 8B-cAMP, an analog of cAMP, but was not affected by Bay K-8644, a selective L-typemore » Ca{sup 2+} channel agonist. These results could be explained by the revised effects of NaHS on isoprenaline-induced cAMP elevation and forskolin-stimulated adenylyl cyclase activity. Additionally, NaHS-induced vasoconstriction was enhanced by removing the endothelium or in the presence of L-NAME, an inhibitor of nitric oxide synthase. L-NAME only partially attenuated the effect of NaHS which was given together with forskolin on the pre-contracted artery. In conclusion, H{sub 2}S induces vasoconstriction of cerebral artery via, at least in part, cAMP/adenylyl cyclase pathway. - Highlights: • The vasoactivity effect of NaHS, a donor of H{sub 2}S, was studied on rat cerebral arteries. • H{sub 2}S induces a constriction, not a relaxant effect on basilar arteries. • The vasoconstrictive effect is invovled in inhibiting adenylyl cyclase to reduce cAMP levels. • The vasoconstriction is partially antagonized by NO, and does not necessarily act via NO pathway.« less

  12. A Single Bout of High-Intensity Interval Training Reduces Awareness of Subsequent Hypoglycemia in Patients With Type 1 Diabetes.

    PubMed

    Rooijackers, Hanne M; Wiegers, Evita C; van der Graaf, Marinette; Thijssen, Dick H; Kessels, Roy P C; Tack, Cees J; de Galan, Bastiaan E

    2017-07-01

    High-intensity interval training (HIIT) has gained increasing popularity in patients with diabetes. HIIT acutely increases plasma lactate levels. This may be important, since the administration of lactate during hypoglycemia suppresses symptoms and counterregulation while preserving cognitive function. We tested the hypothesis that, in the short term, HIIT reduces awareness of hypoglycemia and attenuates hypoglycemia-induced cognitive dysfunction. In a randomized crossover trial, patients with type 1 diabetes and normal awareness of hypoglycemia (NAH), patients with impaired awareness of hypoglycemia (IAH), and healthy participants ( n = 10 per group) underwent a hyperinsulinemic-hypoglycemic (2.6 mmol/L) clamp, either after a HIIT session or after seated rest. Compared with rest, HIIT reduced symptoms of hypoglycemia in patients with NAH but not in healthy participants or patients with IAH. HIIT attenuated hypoglycemia-induced cognitive dysfunction, which was mainly driven by changes in the NAH subgroup. HIIT suppressed cortisol and growth hormone responses, but not catecholamine responses to hypoglycemia. The present findings demonstrate that a single HIIT session rapidly reduces awareness of subsequent hypoglycemia in patients with type 1 diabetes and NAH, but does not in patients with IAH, and attenuates hypoglycemia-induced cognitive dysfunction. The role of exercise-induced lactate in mediating these effects, potentially serving as an alternative fuel for the brain, should be further explored. © 2017 by the American Diabetes Association.

  13. Protective effects of hydrogen sulfide on chronic kidney disease by reducing oxidative stress, inflammation and apoptosis

    PubMed Central

    Askari, Hassan; Seifi, Behjat; Kadkhodaee, Mehri; Sanadgol, Nima; Elshiekh, Mohammed; Ranjbaran, Mina; Ahghari, Parisa

    2018-01-01

    The current study aimed to examine the renoprotective effects of long-term treatment with sodium hydrosulfide (NaHS), a prominent hydrogen sulfide donor, in 5/6 nephrectomy animal model. Twenty-four rats were randomly divided into 3 groups including sham-operated group (Sham), 5/6-nephrectomized group (5/6 Nx), and NaHS-treated group (5/6Nx+NaHS). NaHS (30 micromol/l) was added twice daily into the drinking water and renal failure was induced by 5/6 nephrectomy. Twelve weeks after surgical procedure, blood pressure, creatinine clearance (CCr), urine concentration of neutrophil gelatinase associated lipocalin (NGAL) and tissue concentration of malondialdehyde (MDA), superoxide dismutase (SOD), as well as renal morphological changes, apoptosis (cleaved caspase-3) and inflammation (p-NF-κB) were measured. Five-sixth nephrectomy induced severe renal damage as indicated by renal dysfunction, hypertension and significant histopathological injury which were associated with increased NGAL and MDA levels, oxidant/antioxidant imbalance, decreased SOD activity and CCr and also overexpression of p-NF-κB and cleaved caspase-3 proteins. Instead, NaHS treatment attenuated renal dysfunction through reduction of NGAL concentration, hypertension, CCr, oxidant/antioxidant imbalance, inflammation and apoptosis. These findings suggest that long term NaHS treatment can be useful in preventing the progression of CKD by improving oxidant/antioxidant balance and reducing inflammation and apoptosis in the kidney. PMID:29383015

  14. Hydrogen sulfide ameliorates subarachnoid hemorrhage-induced neuronal apoptosis via the ROS-MST1 pathway

    PubMed Central

    Shi, Ligen; Lei, Jianwei; Xu, Hangzhe; Zheng, Jingwei; Wang, Yan; Peng, Yucong; Yu, Jun; Zhang, Jianmin

    2017-01-01

    Background Hydrogen sulfide (H2S) has shown a neuroprotective role in several cerebrovascular diseases. This study aimed to explore the underlying mechanisms of H2S in early brain injury after subarachnoid hemorrhage (SAH). Methods One hundred seventy-seven male Sprague-Dawley rats were employed in this study. Sodium hydrosulfide (NaHS), a donor of H2S, was injected intraperitoneally at 60 min after SAH was induced by endovascular perforation. Western blot analysis determined the expression of several proteins of interest, and an immunofluorescence assay was used to examine neuronal apoptosis. Results Exogenous NaHS markedly improved neurological scores, attenuated brain edema, and ameliorated neuronal apoptosis at 24 h after SAH induction. The underlying mechanisms of H2S in ameliorating neuronal apoptosis might be executed through inhibition of the activity of mammalian sterile 20-like kinase 1 (MST1) protein. Western blot analysis demonstrated that exogenous NaHS decreased cleaved MST1 (cl-MST1) while increasing full-length MST1 expression. This anti-apoptotic effect of H2S could be reversed by chelerythrine, which could activate MST1 via caspase-dependent cleavage. Conclusions Exogenous NaHS, as a donor of H2S, could ameliorate early brain injury after SAH by inhibiting neuronal apoptosis by reducing the activity of the MST1 protein. PMID:29088725

  15. Effects of hydrogen sulfide on high glucose-induced glomerular podocyte injury in mice

    PubMed Central

    Liu, Ye; Zhao, Huichen; Qiang, Ye; Qian, Guanfang; Lu, Shengxia; Chen, Jicui; Wang, Xiangdong; Guan, Qingbo; Liu, Yuantao; Fu, Yuqin

    2015-01-01

    The aim of this study was to assess the effects of hydrogen sulfide on high glucose-induced mouse podocyte (MPC) injury and the underlying mechanisms. Mouse podocytes were randomly divided into 4 groups, including high glucose (HG), normal glucose (NG), normal glucose + DL-propargylglycine (PPG), and high glucose + NaHS (HG + NaHS) groups for treatment. Then, ZO-2, nephrin, β-catenin, and cystathionine γ-lyase (CSE) protein expression levels were determined by western blot. We found that high glucose significantly reduced nephrin, ZO-2, and CSE expression levels (P<0.05), and overtly elevated β-catenin amounts (P<0.05), in a time-dependent manner. Likewise, PPG at different concentrations in normal glucose resulted in significantly lower CSE, ZO-2, and nephrin levels (P<0.05), and increased β-catenin amounts (P<0.05). Interestingly, significantly increased ZO-2 and nephrin levels, and overtly reduced β-catenin amounts were observed in the HG + NaHS group compared with HG treated cells (P<0.01). Compared with NG treated cells, decreased ZO-2 and nephrin levels and higher β-catenin amounts were obtained in the HG + NaHS group. In conclusion,CSE downregulation contributes to hyperglycemia induced podocyte injury, which is alleviated by exogenous H2S possibly through ZO-2 upregulation and the subsequent suppression of Wnt/β-catenin pathway. PMID:26261567

  16. Abscisic acid induction of vacuolar H+-ATPase activity in mesembryanthemum crystallinum is developmentally regulated

    PubMed

    Barkla; Vera-Estrella; Maldonado-Gama; Pantoja

    1999-07-01

    Abscisic acid (ABA) has been implicated as a key component in water-deficit-induced responses, including those triggered by drought, NaCl, and low- temperature stress. In this study a role for ABA in mediating the NaCl-stress-induced increases in tonoplast H+-translocating ATPase (V-ATPase) and Na+/H+ antiport activity in Mesembryanthemum crystallinum, leading to vacuolar Na+ sequestration, were investigated. NaCl or ABA treatment of adult M. crystallinum plants induced V-ATPase H+ transport activity, and when applied in combination, an additive effect on V-ATPase stimulation was observed. In contrast, treatment of juvenile plants with ABA did not induce V-ATPase activity, whereas NaCl treatment resulted in a similar response to that observed in adult plants. Na+/H+ antiport activity was induced in both juvenile and adult plants by NaCl, but ABA had no effect at either developmental stage. Results indicate that ABA-induced changes in V-ATPase activity are dependent on the plant reaching its adult phase, whereas NaCl-induced increases in V-ATPase and Na+/H+ antiport activity are independent of plant age. This suggests that ABA-induced V-ATPase activity may be linked to the stress-induced, developmentally programmed switch from C3 metabolism to Crassulacean acid metabolism in adult plants, whereas, vacuolar Na+ sequestration, mediated by the V-ATPase and Na+/H+ antiport, is regulated through ABA-independent pathways.

  17. Hydrogen Sulfide Recruits Macrophage Migration by Integrin β1-Src-FAK/Pyk2-Rac Pathway in Myocardial Infarction

    NASA Astrophysics Data System (ADS)

    Miao, Lei; Xin, Xiaoming; Xin, Hong; Shen, Xiaoyan; Zhu, Yi-Zhun

    2016-03-01

    Myocardial infarction (MI) triggers an inflammatory reaction, in which macrophages are of key importance for tissue repairing. Infiltration and/or migration of macrophages into the infarct area early after MI is critical for infarct healing, vascularization, and cardiac function. Hydrogen sulfide (H2S) has been demonstrated to possess cardioprotective effects post MI and during the progress of cardiac remodeling. However, the specific molecular and cellular mechanisms involved in macrophage recruitment by H2S remain to be identified. In this study, the NaHS (exogenous sources of H2S) treatment exerted an increased infiltration of macrophages into the infarcted myocardium at early stage of MI cardiac tissues in both wild type (WT) and cystathionine-γ-lyase-knockout (CSE-KO) mice. And NaHS accelerated the migration of macrophage cells in vitro. While, the inhibitors not only significantly diminished the migratory ability in response to NaHS, but also blocked the activation of phospho-Src, -Pyk2, -FAK397, and -FAK925. Furthermore, NaHS induced the internalization of integrin β1 on macrophage surface, but, integrin β1 silencing inhibited macrophage migration and Src signaling activation. These results indicate that H2S may have the potential as an anti-infarct of MI by governing macrophage migration, which was achieved by accelerating internalization of integrin β1 and activating downstream Src-FAK/Pyk2-Rac pathway.

  18. Vermittlungstechnik

    NASA Astrophysics Data System (ADS)

    Plaßmann, Wilfried

    In einem vorhandenen Nachrichtennetz sorgt die Vermittlungstechnik dafür, dass Informationen zu jeder Zeit von einem beliebigen Zugangspunkt zu einem beliebigen anderen Zugangspunkt übertragen werden können. Der gesamte Vorgang wird mit Vermittlung bezeichnet. Das größte weltweit vorhandene Nachrichtennetz ist das kombinierte Internet-Telefonnetz. Die Zugangspunkte sind die Anschlusspunkte (ortsfeste Anschlussdosen) für die Endgeräte, wie z. B. Rechner, Telefonapparate, Faxgeräte oder Modems, oder aber ortsveränderliche Endgeräte wie Laptops, schnurlose Telefone oder Funktelefone ("Handys"). Die Vermittlungsstelle klassischer Art mit hierarchischem Aufbau ist nahezu vollständig durch komplexe rechnergesteuerte national arbeitende Anlagen ersetzt worden. In diesem Kapitel werden deshalb grundlegende Eigenschaften dargestellt. Stichworte: Grundbegriffe; Vermittlung; Verkehrstheorie; Endgeräte.

  19. Grundlegende Steuerungsverfahren im heterogenen Logistiknetz mit Kanban

    NASA Astrophysics Data System (ADS)

    Dickmann, Eva; Dickmann, Philipp; Lödding, Hermann; Möller, Niklas; Rücker, Thomas; Schneider, Herfried M.; Zäh, Michael F.

    In vielen Unternehmen werden heterogene (verschiedene) Steuerungen in einem abgestimmten Konzept kombiniert. Je nach Anwendungsfall und Rahmenbedingungen werden Kombinationen allgemein bekannter Steuerungen oder Steuerungsvarianten gemischt eingesetzt, um eine optimale Steuerung für unterschiedliche Fälle zu erreichen. Hierbei stehen neben den bekannten und weit verbreiteten Methoden, wie Material Requirements Planning (MRP) oder Kanban, auch weniger bekannte oder neue Methoden zur Auswahl, wie die Produktionssteuerung mit dezentraler, bestandsorientierter Fertigungsregelung (DBF). Kanban ist ein simples und effizientes Steuerungskonzept, das in der klassischen Form für spezifische einfache Anwendungsfälle umsetzbar ist. Hochentwickelte Steuerungsalgorithmen können helfen, komplexe Abläufe optimal abzubilden. Mit einer grundlegenden Vereinfachung der Abläufe kann allerdings in vielen Fällen ein wesentlich stärkerer und umfassender Verbesserungseffekt erzielt werden. Die wesentliche Fragestellung sollte folglich lauten: Warum ist der Ablauf nicht mit einer einfachen Steuerung wie Kanban abzubilden? Um die Vorteile des Konzepts auch in untypischen Bereichen anwenden zu können, sind jedoch verschiedene Varianten oder Kanban-ähnliche Steuerungsmethoden entstanden. Darüber hinaus sind in der Praxis hybride Steuerungen im Einsatz, welche so kombiniert werden, dass die Zusammensetzung anspruchsvolle Eigenschaftsbilder noch exakt abbildet. In der Praxis basieren die Steuerungsentscheidungen nur zu einem kleinen Teil auf den eigentlichen Steuerungsalgorithmen, wie sie uns das MRP-System zur Verfügung stellt. Moderne Steuerungswelten" schließen alle relevanten Informationsquellen in eine heterogene Entscheidungsmatrix mit ein. Letztlich zählt nicht, ob die Entscheidung auf den Informationen aus dem MRP-System oder auf Softfacts basierend getroffen wurde, sondern nur, ob die Entscheidung erfolgreich war.

  20. PVD-Beschichtungstechnologie

    NASA Astrophysics Data System (ADS)

    Lake, Markus K.

    Die PVD-Technologie umfasst eine Reihe von Beschichtungsverfahren zur Abscheidung von Metallen, Legierungen oder chemischen Verbindungen durch Zufuhr von thermischer Energie oder durch Teilchenbeschuss im Hochvakuum. PVDVerfahren gestatten u. a. die Beschichtung bei niedrigen Prozesstemperaturen, so dass thermisch sensible Substrate, z. B. wärmebehandelte Stähle oder ausgewählte Kunststoffe, beschichtet werden können. Insbesondere mit dem Magnetron Sputter Ion Plating-Verfahren (MSIP-Verfahren) und mit dem Arc Ion Plating-Verfahren (AIP-Verfahren) ist es möglich, thermisch vorbehandelte Werkstoffe zu beschichten, ohne den eingestellten Wärmebehandlungszustand (Härte, Spannungszustand) zu verändern. Ferner können endbearbeitete Bauteile mit der PVD-Technologie beschichtet werden, da die eingesetzten PVD-Verfahren die Ausgangsoberfläche konturgetreu abbilden, ohne dass eine Nachbearbeitung erforderlich wird.

  1. Critical periods in the variation in body composition in school children.

    PubMed

    Cristi-Montero, Carlos; Bresciani, Guilherme; Alvarez, Ana; Arriagada, Valentina; Beneventi, Angelo; Canepa, Valentina; Espinoza, Paula; Parraguez, Melisa; Toledo, Carlos; Valencia, Consuelo; Rodriguez-Rodriguez, Fernando

    2014-10-01

    To identify critical periods in the variation in body composition during a school year and determine possible causes. A total of 363 boys and girls aged between 10 and 14 years participated in the study. Before and after the Winter Holidays (WIH) and National Holidays (NAH) (July and September, respectively), measurements were taken of body weight, body fat percentage, waist perimeter, time spent on physical activity and hours of sleep in order to determine the variations. The normality of the data was confirmed and the means were compared with an alpha significance level of p<0.05. The school children increased in weight by 600 g and 510 g in the NAH and WIH, respectively (p<0.0001), and their body fat percentage was significantly increased during both periods (0.51%); however, the waist perimeter measurement saw no significant changes. It can also be seen that in NAH physical activity dropped by an important amount (-41 min, p<0.0001), though this did not occur in WIH. A significant increase in hours of sleep was also seen during the two holiday periods (~1 to 2 hours/day). It is concluded that both NAH and WIH can be considered critical periods due to the sharp increase in body weight and body fat percentage in the school children, where a possible cause is the reduction in time spent on physical activity. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

  2. Reactions of tobacco genotypes with different antioxidant capacities to powdery mildew and Tobacco mosaic virus infections.

    PubMed

    Gullner, Gábor; Juhász, Csilla; Németh, Adél; Barna, Balázs

    2017-10-01

    The interactions of powdery mildew (Golovinomyces orontii) and Tobacco mosaic virus (TMV) with tobacco lines having down or upregulated antioxidants were investigated. Xanthi-nc, its salicylic acid-deficient NahG mutant, a paraquat-sensitive Samsun (PS) and its paraquat tolerant (PT) mutant were used. Cell membrane damage caused by H 2 O 2 was significantly higher in NahG than Xanthi, whereas it was lower in PT than in PS. Leakage of ions from PT was reduced by the powdery mildew infection. On the other hand TMV inoculation led to a 6-fold and 2-fold elevation of ion leakage from hypersensitive resistant NahG and Xanthi leaves, respectively, whereas ion leakage increased slightly from susceptible PS leaves. G. orontii infection induced ribonuclease (RNase) enzyme activity in extracts from Xanthi and NahG (about 200-250% increase) and weakly (about 20-30% increase) from PS and PT lines. Pre-treatment with protein kinase inhibitor staurosporine or protein phosphatase inhibitor okadaic acid very strongly inhibited mildew development on tobacco lines. Our experiments suggest that protein kinases inhibited by staurosporine seem to be important factors, while protein phosphatases inhibited by okadaic acid play less significant role in TMV-induced lesion development. Both powdery mildew and TMV infections up-regulated the expression of PR-1b, PR-1c and WRKY12 genes in all tobacco lines to various extents. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  3. Abscisic Acid Induction of Vacuolar H+-ATPase Activity in Mesembryanthemum crystallinum Is Developmentally Regulated1

    PubMed Central

    Barkla, Bronwyn J.; Vera-Estrella, Rosario; Maldonado-Gama, Minerva; Pantoja, Omar

    1999-01-01

    Abscisic acid (ABA) has been implicated as a key component in water-deficit-induced responses, including those triggered by drought, NaCl, and low- temperature stress. In this study a role for ABA in mediating the NaCl-stress-induced increases in tonoplast H+-translocating ATPase (V-ATPase) and Na+/H+ antiport activity in Mesembryanthemum crystallinum, leading to vacuolar Na+ sequestration, were investigated. NaCl or ABA treatment of adult M. crystallinum plants induced V-ATPase H+ transport activity, and when applied in combination, an additive effect on V-ATPase stimulation was observed. In contrast, treatment of juvenile plants with ABA did not induce V-ATPase activity, whereas NaCl treatment resulted in a similar response to that observed in adult plants. Na+/H+ antiport activity was induced in both juvenile and adult plants by NaCl, but ABA had no effect at either developmental stage. Results indicate that ABA-induced changes in V-ATPase activity are dependent on the plant reaching its adult phase, whereas NaCl-induced increases in V-ATPase and Na+/H+ antiport activity are independent of plant age. This suggests that ABA-induced V-ATPase activity may be linked to the stress-induced, developmentally programmed switch from C3 metabolism to Crassulacean acid metabolism in adult plants, whereas, vacuolar Na+ sequestration, mediated by the V-ATPase and Na+/H+ antiport, is regulated through ABA-independent pathways. PMID:10398716

  4. Hydrogen sulfide enhances salt tolerance through nitric oxide-mediated maintenance of ion homeostasis in barley seedling roots

    PubMed Central

    Chen, Juan; Wang, Wen-Hua; Wu, Fei-Hua; He, En-Ming; Liu, Xiang; Shangguan, Zhou-Ping; Zheng, Hai-Lei

    2015-01-01

    Hydrogen sulfide (H2S) and nitric oxide (NO) are emerging as messenger molecules involved in the modulation of plant physiological processes. Here, we investigated a signalling network involving H2S and NO in salt tolerance pathway of barley. NaHS, a donor of H2S, at a low concentration of either 50 or 100 μM, had significant rescue effects on the 150 mM NaCl-induced inhibition of plant growth and modulated the K+/Na+ balance by decreasing the net K+ efflux and increasing the gene expression of an inward-rectifying potassium channel (HvAKT1) and a high-affinity K+ uptake system (HvHAK4). H2S and NO maintained the lower Na+ content in the cytoplast by increasing the amount of PM H+-ATPase, the transcriptional levels of PM H+-ATPase (HvHA1) and Na+/H+ antiporter (HvSOS1). H2S and NO modulated Na+ compartmentation into the vacuoles with up-regulation of the transcriptional levels of vacuolar Na+/H+ antiporter (HvVNHX2) and H+-ATPase subunit β (HvVHA-β) and increased in the protein expression of vacuolar Na+/H+ antiporter (NHE1). H2S mimicked the effect of sodium nitroprusside (SNP) by increasing NO production, whereas the function was quenched with the addition of NO scavenger. These results indicated that H2S increased salt tolerance by maintaining ion homeostasis, which were mediated by the NO signal. PMID:26213372

  5. Single gene deletions of mrpA to mrpG and mrpE point mutations affect activity of the Mrp Na+/H+ antiporter of alkaliphilic Bacillus and formation of hetero-oligomeric Mrp complexes.

    PubMed

    Morino, Masato; Natsui, Shinsuke; Swartz, Talia H; Krulwich, Terry A; Ito, Masahiro

    2008-06-01

    Mrp antiporters catalyze secondary Na(+)(Li(+))/H(+) antiport and/or K(+)/H(+) antiport that is physiologically important in diverse bacteria. An additional capacity for anion flux has been observed for a few systems. Mrp is unique among antiporters in that it requires all six or seven hydrophobic gene products (MrpA to MrpG) of the mrp operon for full antiporter activity, but MrpE has been reported to be dispensable. Here, the membrane complexes formed by Mrp proteins were examined using a cloned mrp operon from alkaliphilic Bacillus pseudofirmus OF4. The operon was engineered so that the seven Mrp proteins could be detected in single samples. Membrane extracts of an antiporter-deficient Escherichia coli strain expressing this construct were analyzed by blue native-sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Mrp complexes of two sizes were identified containing all seven Mrp proteins. Studies of the single nonpolar mrp gene deletions in the construct showed that a subcomplex of MrpA, MrpB, MrpC, and MrpD was formed in the absence of MrpE, MrpF, or MrpG. By contrast, MrpE, MrpF, and MrpG were not observed in membranes lacking MrpA, MrpB, MrpC, or MrpD. Although MrpA and MrpD have been hypothesized to be the antiporter proteins, the MrpA-to-D complex was inactive. Every Mrp protein was required for an activity level near that of the wild-type Na(+)/H(+) antiporter, but a very low activity level was observed in the absence of MrpE. The introduction of an MrpE(P114G) mutation into the full Mrp complex led to antiport activity with a greatly increased apparent K(m) value for Na(+). The results suggested that interactions among the proteins of heterooligomeric Mrp complexes strongly impact antiporter properties.

  6. Praktische Festigkeitsberechnungen im Maschinenbau

    NASA Astrophysics Data System (ADS)

    Böge, Gert; Böge, Wolfgang

    Ziel aller Festigkeitsberechnungen ist die Ermittlung der vorhandenen Spannung und der Nachweis, dass ein konstruiertes Bauteil mit Sicherheit "hält". Seine geforderte oder erwartete Tragfähigkeit muss unter allen denkbaren Umständen gewährleistet sein, es darf z. B. auch bei Dauerbelastung in der vorgeschriebenen Lebensdauer nicht brechen oder seine Form bleibend so verändern, dass es seine Funktion nicht mehr ausreichend erfüllt.

  7. A cluster ion chemistry for the mesospheric sodium layer

    NASA Technical Reports Server (NTRS)

    Richter, E. S.; Sechrist, C. F., Jr.

    1979-01-01

    A cluster ion chemistry for sodium is developed which relates the Na(+) profile to the Na profile using reactions involving Na(+).N2, Na(+).CO2, and Na(+).H2O. Removal of sodium from the mesosphere is accomplished by the formation of higher order clusters of the form Na(+).(H2O)n which presumably precipitate to the lower atmosphere. This sink is most effective in the 80-85 km altitude range. The chemical equilibrium model is applied to experimental observations of the Na and Na(+) layers.

  8. Hydrogen sulfide epigenetically attenuates homocysteine-induced mitochondrial toxicity mediated through NMDA receptor in mouse brain endothelial (bEnd3) cells†

    PubMed Central

    Kamat, Pradip K.; Kalani, Anuradha; Tyagi, Suresh C.; Tyagi, Neetu

    2014-01-01

    Previously we have showed that homocysteine (Hcy) caused oxidative stress and altered mitochondrial function. Hydrogen sulphide (H2S) has potent anti-inflammatory, anti-oxidative and anti-apoptotic effects. Therefore, in the present study we examined whether H2S ameliorates Hcy-induced mitochondrial toxicity which led to endothelial dysfunction in part, by epigenetic alterations in mouse brain endothelial cells (bEnd3). The bEnd3 cells were exposed to 100μM Hcy treatment in the presence or absence of 30μM NaHS (donor of H2S) for 24hrs. Hcy-activate NMDA receptor and induced mitochondrial toxicity by increased levels of Ca2+, NADPH-oxidase-4 (NOX-4) expression, mitochondrial dehydrogenase activity and decreased the level of nitrate, superoxide dismutase (SOD-2) expression, mitochondria membrane potentials, ATP production. To confirm the role of epigenetic, 5′-azacitidine (an epigenetic modulator) treatment was given to the cells. Pretreatment with NaHS (30μM) attenuated the Hcy-induced increased expression of DNMT1, DNMT3a, Ca2+ and decreased expression of DNMT3b in bEND3 cells. Furthermore, NaHS treatment also enhanced mitochondrial oxidative stress (NOX4, ROS, and NO) and restored ATP that indicates its protective effects against mitochondrial toxicity. Additional, NaHS significantly alleviated Hcy-induced LC3-I/II, CSE, Atg3/7 and low p62 expression which confirm its effect on mitophagy. Likewise, NaHS also restored level of eNOS, CD31, VE-Cadherin and ET-1 and maintains endothelial function in Hcy treated cells. Molecular inhibition of NMDA receptor by using small interfering RNA showed protective effect whereas inhibition of H2S production by propargylglycine (PG) (inhibitor of enzyme CSE) showed mitotoxic effect. Taken together, results demonstrate that, administration of H2S protected the cells from HHcy-induced mitochondrial toxicity and endothelial dysfunction. PMID:25056869

  9. Hydrogen Sulfide Epigenetically Attenuates Homocysteine-Induced Mitochondrial Toxicity Mediated Through NMDA Receptor in Mouse Brain Endothelial (bEnd3) Cells.

    PubMed

    Kamat, Pradip K; Kalani, Anuradha; Tyagi, Suresh C; Tyagi, Neetu

    2015-02-01

    Previously we have shown that homocysteine (Hcy) caused oxidative stress and altered mitochondrial function. Hydrogen sulfide (H2S) has potent anti-inflammatory, anti-oxidative, and anti-apoptotic effects. Therefore, in the present study we examined whether H2S ameliorates Hcy-induced mitochondrial toxicity which led to endothelial dysfunction in part, by epigenetic alterations in mouse brain endothelial cells (bEnd3). The bEnd3 cells were exposed to 100 μM Hcy treatment in the presence or absence of 30 μM NaHS (donor of H2S) for 24 h. Hcy-activate NMDA receptor and induced mitochondrial toxicity by increased levels of Ca(2+), NADPH-oxidase-4 (NOX-4) expression, mitochondrial dehydrogenase activity and decreased the level of nitrate, superoxide dismutase (SOD-2) expression, mitochondria membrane potentials, ATP production. To confirm the role of epigenetic, 5'-azacitidine (an epigenetic modulator) treatment was given to the cells. Pretreatment with NaHS (30 μM) attenuated the Hcy-induced increased expression of DNMT1, DNMT3a, Ca(2+), and decreased expression of DNMT3b in bEND3 cells. Furthermore, NaHS treatment also mitigated mitochondrial oxidative stress (NOX4, ROS, and NO) and restored ATP that indicates its protective effects against mitochondrial toxicity. Additional, NaHS significantly alleviated Hcy-induced LC3-I/II, CSE, Atg3/7, and low p62 expression which confirm its effect on mitophagy. Likewise, NaHS also restored level of eNOS, CD31, VE-cadherin and ET-1 and maintains endothelial function in Hcy treated cells. Molecular inhibition of NMDA receptor by using small interfering RNA showed protective effect whereas inhibition of H2S production by propargylglycine (PG) (inhibitor of enzyme CSE) showed mitotoxic effect. Taken together, results demonstrate that, administration of H2S protected the cells from HHcy-induced mitochondrial toxicity and endothelial dysfunction. © 2014 Wiley Periodicals, Inc.

  10. Negative Effect of Ellagic Acid on Cytosolic pH Regulation and Glycolytic Flux in Human Endometrial Cancer Cells.

    PubMed

    Abdelazeem, Khalid N M; Singh, Yogesh; Lang, Florian; Salker, Madhuri S

    2017-01-01

    Key properties of tumor cells include enhanced glycolytic flux with excessive consumption of glucose and formation of lactate. As glycolysis is highly sensitive to cytosolic pH, maintenance of glycolysis requires export of H+ ions, which is in part accomplished by Na+/H+ exchangers, such as NHE1. The carrier is sensitive to oxidative stress. Growth of tumor cells could be suppressed by the polyphenol Ellagic acid, which is found in various fruits and vegetables. An effect of Ellagic acid on transport processes has, however, never been reported. The present study thus elucidated an effect of Ellagic acid on cytosolic pH (pHi), NHE1 transcript levels, NHE1 protein abundance, Na+/H+ exchanger activity, and lactate release. Experiments were performed in Ishikawa cells without or with prior Ellagic acid (20 µM) treatment. NHE1 transcript levels were determined by qRT-PCR, NHE1 protein abundance by Western blotting, pHi utilizing (2',7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein [BCECF] fluorescence, Na+/H+ exchanger activity from Na+ dependent realkalinization after an ammonium pulse, cell volume from forward scatter in flow cytometry, reactive oxygen species (ROS) from 2',7'-dichlorodihydrofluorescein fluorescence, glucose uptake utilizing 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose, and lactate concentration in the supernatant utilizing a colorimetric (570 nm)/ fluorometric enzymatic assay. A 48 hour treatment with Ellagic acid (20 µM) significantly decreased NHE1 transcript levels by 75%, NHE1 protein abundance by 95%, pHi from 7.24 ± 0.01 to 7.02 ± 0.01, Na+/H+ exchanger activity by 77%, forward scatter by 10%, ROS by 82%, glucose uptake by 58%, and lactate release by 15%. Ellagic acid (20µM) markedly down-regulates ROS formation and NHE1 expression leading to decreased Na+/H+ exchanger activity, pHi, glucose uptake and lactate release in endometrial cancer cells. Those effects presumably contribute to reprogramming and growth

  11. The role of sodium hydrosulfide in attenuating the aging process via PI3K/AKT and CaMKKβ/AMPK pathways.

    PubMed

    Chen, Xubo; Zhao, Xueyan; Cai, Hua; Sun, Haiying; Hu, Yujuan; Huang, Xiang; Kong, Wen; Kong, Weijia

    2017-08-01

    Age-related dysfunction of the central auditory system, known as central presbycusis, is characterized by defects in speech perception and sound localization. It is important to determine the pathogenesis of central presbycusis in order to explore a feasible and effective intervention method. Recent work has provided fascinating insight into the beneficial function of H 2 S on oxidative stress and stress-related disease. In this study, we investigated the pathogenesis of central presbycusis and tried to explore the mechanism of H 2 S action on different aspects of aging by utilizing a mimetic aging rat and senescent cellular model. Our results indicate that NaHS decreased oxidative stress and apoptosis levels in an aging model via CaMKKβ and PI3K/AKT signaling pathways. Moreover, we found that NaHS restored the decreased activity of antioxidants such as GSH, SOD and CAT in the aging model in vivo and in vitro by regulating CaMKKβ and PI3K/AKT. Mitochondria function was preserved by NaHS, as indicated by the following: DNA POLG and OGG-1, the base excision repair enzymes in mitochondrial, were upregulated; OXPHOS activity was downregulated; mitochondrial membrane potential was restored; ATP production was increased; and mtDNA damage, indicated by the common deletion (CD), declined. These effects were also achieved by activating CaMKKβ/AMPK and PI3K/AKT signaling pathways. Lastly, protein homeostasis, indicated by HSP90 alpha, was strengthened by NaHS via CaMKKβ and PI3K/AKT. Our findings demonstrate that the ability to resist oxidative stress and mitochondria function are both decreased as aging developed; however, NaHS, a novel free radical scavenger and mitochondrial protective agent, precludes the process of oxidative damage by activating CaMKKβ and PI3K/AKT. This study might provide a therapeutic target for aging and age-related disease. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  12. Protective Effects of Hydrogen Sulfide in Hypoxic Human Umbilical Vein Endothelial Cells: A Possible Mitochondria-Dependent Pathway

    PubMed Central

    Shen, Yaqi; Guo, Wei; Wang, Zhijun; Zhang, Yuchen; Zhong, Liangjie; Zhu, Yizhun

    2013-01-01

    The aim of the study was to investigate the protective effects of sodium hydrosulfide (NaHS), a H2S donor, against hypoxia-induced injury in human umbilical vein endothelial cells (HUVECs) and also to look into the possible mechanisms by which H2S exerts this protective effect. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and scratch wound healing assay were chosen to measure the cell viability and migration-promoting effects. The fluorescent probe, DCFH-DA and 5,5′,6,6′-Tetrachloro-1,1′,3,3′-tetraethyl-imidacarbocyanine iodide (JC-1) were applied to detect the reactive oxygen species (ROS) level and mitochondrial membrane potential (ΔΨm). Furthermore, western blots were used to measure the expressions of the apoptosis-related proteins. Under hypoxic conditions, 300 μM and 600 μM of H2S could protect HUVECs against hypoxia-induced injury, as determined by MTT assay. Following the treatment of 60 μM NaHS for 18 h, scratch wound healing assays indicated that the scratch became much narrower than control group. After treatment with 60 μM, 120 μM, and 600 μM NaHS, and hypoxia for 30 min, flow cytometry demonstrated that the ROS concentrations decreased to 95.08% ± 5.52%, 73.14% ± 3.36%, and 73.51% ± 3.05%, respectively, compared with the control group. In addition, the JC-1 assay showed NaHS had a protective effect on mitochondria damage. Additionally, NaHS increased Bcl-2 expression and decreased the expression of Bax, Caspase-3 and Caspase-9 in a dose-dependent way. Our results suggest that H2S can protect endothelial cells and promote migration under hypoxic condition in HUVECs. These effects are partially associated with the preservation of mitochondrial function mediated by regulating the mitochondrial-dependent apoptotic pathway. PMID:23799362

  13. A human intervention study with foods containing natural Ah-receptor agonists does not significantly show AhR-mediated effects as measured in blood cells and urine.

    PubMed

    de Waard, Pim W J; Peijnenburg, Ad A C M; Baykus, Hakan; Aarts, Jac M M J G; Hoogenboom, Ron L A P; van Schooten, Frederik J; de Kok, Theo M C M

    2008-10-22

    Binding and activation of the aryl hydrocarbon receptor (AhR) is thought to be an essential step in the toxicity of the environmental pollutants dioxins and dioxin-like PCBs. However, also a number of natural compounds, referred to as NAhRAs (natural Ah-receptor agonists), which are present in, for example, fruits and vegetables, can bind and activate this receptor. To study their potential effects in humans, we first investigated the effect of the prototypical AhR agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on gene expression in ex vivo exposed freshly isolated human lymphocytes, and compared the resulting gene expression profile with those caused by the well-known NAhRA indolo[3,2-b]carbazole (ICZ), originating from cruciferous vegetables, and by a hexane extract of NAhRA-containing grapefruit juice (GJE). Only ICZ induced a gene expression profile similar to TCDD in the lymphocytes, and both significantly up-regulated CYP1B1 and TIPARP (TCDD-inducible poly (ADP-ribose) polymerase) mRNA. Next, we performed a human intervention study with NAhRA-containing cruciferous vegetables and grapefruit juice. The expression of the prototypical AhR-responsive genes CYP1A1, CYP1B1 and NQO1 in whole blood cells and in freshly isolated lymphocytes was not significantly affected. Also enzyme activities of CYP1A2, CYP2A6, N-acetyltransferase 2 (NAT2) and xanthine oxidase (XO), as judged by caffeine metabolites in urine, were unaffected, except for a small down-regulation of NAT2 activity by grapefruit juice. Examination of blood plasma with DR CALUX showed a 12% increased AhR agonist activity 3 and 24 h after consumption of cruciferous vegetables, but did not show a significant effect of grapefruit juice consumption. We conclude that intake of NAhRAs from food may result in minor AhR-related effects measurable in human blood and urine.

  14. Molecular characterization of the Na+/H+-antiporter NhaA from Salmonella Typhimurium.

    PubMed

    Lentes, Christopher J; Mir, Syed H; Boehm, Marc; Ganea, Constanta; Fendler, Klaus; Hunte, Carola

    2014-01-01

    Na+/H+ antiporters are integral membrane proteins that are present in almost every cell and in every kingdom of life. They are essential for the regulation of intracellular pH-value, Na+-concentration and cell volume. These secondary active transporters exchange sodium ions against protons via an alternating access mechanism, which is not understood in full detail. Na+/H+ antiporters show distinct species-specific transport characteristics and regulatory properties that correlate with respective physiological functions. Here we present the characterization of the Na+/H+ antiporter NhaA from Salmonella enterica serovar Thyphimurium LT2, the causing agent of food-born human gastroenteritis and typhoid like infections. The recombinant antiporter was functional in vivo and in vitro. Expression of its gene complemented the Na+-sensitive phenotype of an E. coli strain that lacks the main Na+/H+ antiporters. Purified to homogeneity, the antiporter was a dimer in solution as accurately determined by size-exclusion chromatography combined with multi-angle laser-light scattering and refractive index monitoring. The purified antiporter was fully capable of electrogenic Na+(Li+)/H+-antiport when reconstituted in proteoliposomes and assayed by solid-supported membrane-based electrophysiological measurements. Transport activity was inhibited by 2-aminoperimidine. The recorded negative currents were in agreement with a 1Na+(Li+)/2H+ stoichiometry. Transport activity was low at pH 7 and up-regulation above this pH value was accompanied by a nearly 10-fold decrease of KmNa (16 mM at pH 8.5) supporting a competitive substrate binding mechanism. K+ does not affect Na+ affinity or transport of substrate cations, indicating that selectivity of the antiport arises from the substrate binding step. In contrast to homologous E. coli NhaA, transport activity remains high at pH values above 8.5. The antiporter from S. Typhimurium is a promising candidate for combined structural and

  15. Molecular Characterization of the Na+/H+-Antiporter NhaA from Salmonella Typhimurium

    PubMed Central

    Lentes, Christopher J.; Mir, Syed H.; Boehm, Marc; Ganea, Constanta; Fendler, Klaus; Hunte, Carola

    2014-01-01

    Na+/H+ antiporters are integral membrane proteins that are present in almost every cell and in every kingdom of life. They are essential for the regulation of intracellular pH-value, Na+-concentration and cell volume. These secondary active transporters exchange sodium ions against protons via an alternating access mechanism, which is not understood in full detail. Na+/H+ antiporters show distinct species-specific transport characteristics and regulatory properties that correlate with respective physiological functions. Here we present the characterization of the Na+/H+ antiporter NhaA from Salmonella enterica serovar Thyphimurium LT2, the causing agent of food-born human gastroenteritis and typhoid like infections. The recombinant antiporter was functional in vivo and in vitro. Expression of its gene complemented the Na+-sensitive phenotype of an E. coli strain that lacks the main Na+/H+ antiporters. Purified to homogeneity, the antiporter was a dimer in solution as accurately determined by size-exclusion chromatography combined with multi-angle laser-light scattering and refractive index monitoring. The purified antiporter was fully capable of electrogenic Na+(Li+)/H+-antiport when reconstituted in proteoliposomes and assayed by solid-supported membrane-based electrophysiological measurements. Transport activity was inhibited by 2-aminoperimidine. The recorded negative currents were in agreement with a 1Na+(Li+)/2H+ stoichiometry. Transport activity was low at pH 7 and up-regulation above this pH value was accompanied by a nearly 10-fold decrease of Km Na (16 mM at pH 8.5) supporting a competitive substrate binding mechanism. K+ does not affect Na+ affinity or transport of substrate cations, indicating that selectivity of the antiport arises from the substrate binding step. In contrast to homologous E. coli NhaA, transport activity remains high at pH values above 8.5. The antiporter from S. Typhimurium is a promising candidate for combined structural and

  16. Suitability of oral administration of monosodium phosphate, disodium phosphate, and magnesium phosphate for the rapid correction of hypophosphatemia in cattle.

    PubMed

    Cohrs, Imke; Grünberg, Walter

    2018-05-01

    Hypophosphatemia is commonly associated with disease and decreased productivity in dairy cows particularly in early lactation. Oral supplementation with phosphate salts is recognized as suitable for the rapid correction of hypophosphatemia. Little information is available about the differences in efficacy between salts used for oral phosphorus supplementation. Comparison of efficacy of oral administration of NaH 2 PO 4 , Na 2 HPO 4 , and MgHPO 4 in treating hypophosphatemia in cattle. 12 healthy dairy cows in the fourth week of lactation in their second to fifth lactation. Randomized clinical study. Phosphorus deficient, hypophosphatemic cows underwent a sham treatment and were afterwards assigned to 1 of 3 treatments-NaH 2 PO 4 , Na 2 HPO 4 , or MgHPO 4 (each provided the equivalent of 60 g of phosphorus). Blood samples were obtained immediately before and repeatedly after treatment. Treatment with NaH 2 PO 4 and Na 2 HPO 4 resulted in rapid and sustained increases of plasma phosphate concentrations ([Pi]). Significant effects were apparent within 1 hour (NaH 2 PO 4 : P = .0044; Na 2 HPO 4 : P = .0077). Peak increments of plasma [Pi] of 5.33 mg/dL [5.26-5.36] and 4.30 mg/dL [3.59-4.68] (median and interquartile range) were reached after 7 and 6 hours in animals treated with NaPH 2 PO 4 and Na 2 HPO 4 , respectively, whereas treatment with MgHPO 4 led to peak increments 14 hours after treatment (3.19 mg/dL [2.11-4.04]). NaH 2 PO 4 and Na 2 HPO 4 are suitable to rapidly correct hypophosphatemia in cattle. Because of the protracted and weaker effect, MgHPO 4 cannot be recommended for this purpose. Despite important differences in solubility of NaH 2 PO 4 and Na 2 HPO 4 only small plasma [Pi] differences were observed after treatment. Copyright © 2018 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  17. Vernarbende Alopezien.

    PubMed

    Kanti, Varvara; Röwert-Huber, Joachim; Vogt, Annika; Blume-Peytavi, Ulrike

    2018-04-01

    Primär vernarbende Alopezien (PVA) werden nach der Klassifikation der North American Hair Research Society nach ihrem prominenten entzündlichen Infiltrat in vier Gruppen eingeteilt: PVA mit lymphozytärem, neutrophilem, gemischtzelligem oder unspezifischem Entzündungsmuster. Der Haarausfall kann subklinisch beginnen und langsam fortschreiten, so dass der genaue Erkrankungsbeginn oft schwer nachzuvollziehen ist. Die Diagnose wird häufig verzögert gestellt. Während die meisten vernarbenden Alopezien bei vollständiger Ausprägung anhand des klinischen Bildes klar zugeordnet werden können, ist die Diagnosestellung in der Frühphase oder im Endstadium häufig schwierig. Bei Erstvorstellung sollte eine ausführliche Anamnese und dermatologische Ganzkörperuntersuchung, inklusive Trichoskopie durchgeführt werden. In klinisch unklaren Fällen sollte eine Biopsie erfolgen. Aufgrund der Seltenheit der PVA gibt es bisher nur eine niedrige Evidenz über die Wirksamkeiten der Vielzahl der verschiedenen angewandten Therapien. Ziele der Therapie einer PVA sind, den Haarausfall zu stoppen oder zumindest zu verzögern, die klinischen Entzündungszeichen zu reduzieren, weitere Vernarbung zu verhindern sowie die subjektiven Symptome zu lindern. Ein Nachwachsen in bereits vernarbten Arealen sollte nicht erwartet werden. Eine antientzündliche Therapie mit topischen Kortikosteroiden der Klasse III-IV und/oder mit intrakutanen intraläsionalen Triamcinolonacetonid-Injektionen kommt bei den meisten PVA in Betracht. Die Wahl der systemischen Therapie hängt von der Art des prädominierenden entzündlichen Infiltrates ab und umfasst antimikrobielle/antibiotische oder immunmodulatorische/immunsuppressive Ansätze. Psychologische Unterstützung und Camouflage-Techniken sollten den Patienten angeboten werden. © 2018 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

  18. Niederschlag

    NASA Astrophysics Data System (ADS)

    Kunz, Michael; Mohr, Susanna; Werner, Peter C.

    Niederschlag kann in flüssiger Form als Niesel oder Regen oder in gefrorener, fester Form als Graupel, Hagel oder Schnee fallen. Durch die globale Erwärmung intensiviert sich der Wasserkreislauf, was zu einer Veränderung der Niederschlagsmuster führt. Außerdem ist zu erwarten, dass sich im Zuge des Klimawandels auch die Häufigkeit bestimmter Wetterlagen ändern wird, die das Niederschlagsgeschehen grundsätzlich bestimmen. Bereits heute ist in Deutschland eine Änderung der Niederschlagsaktivität zu beobachten. Das Kapitel beschäftigt sich neben den sommerlichen und winterlichen Starkniederschlagsereignissen auch mit Hagelereignissen und dem Schneefall. Neben einer Zusammenfassung der bereits beobachteten Änderungen dieser Niederschlagsformen in der Vergangenheit wird auch der Frage nachgegangen, inwieweit man für diese Ereignisse belastbare Aussagen für die Zukunft treffen kann.

  19. In vitro susceptibility to quinine and microsatellite variations of the Plasmodium falciparum Na+/H+ exchanger (Pfnhe-1) gene: the absence of association in clinical isolates from the Republic of Congo

    PubMed Central

    2011-01-01

    Background Quinine is still recommended as an effective therapy for severe cases of Plasmodium falciparum malaria, but the parasite has developed resistance to the drug in some cases. Investigations into the genetic basis for quinine resistance (QNR) suggest that QNR is complex and involves several genes, with either an additive or a pairwise effect. The results obtained when assessing one of these genes, the plasmodial Na+/H+ exchanger, Pfnhe-1, were found to depend upon the geographic origin of the parasite strain. Most of the associations identified have been made in Asian strains; in contrast, in African strains, the influence of Pfnhe on QNR is not apparent. However, a recent study carried out in Kenya did show a significant association between a Pfnhe polymorphism and QNR. As genetic differences may exist across the African continent, more field data are needed to determine if this association exists in other African regions. In the present study, association between Pfnhe and QNR is investigated in a series of isolates from central Africa. Methods The sequence analysis of the polymorphisms at the Pfnhe-1 ms4760 microsatellite and the evaluation of in vitro quinine susceptibility (by isotopic assay) were conducted in 74 P. falciparum isolates from the Republic of Congo. Results Polymorphisms in the number of DNNND or NHNDNHNNDDD repeats in the Pfnhe-1 ms4760 microsatellite were not associated with quinine susceptibility. Conclusions The polymorphism in the microsatellite ms4760 in Pfnhe-1 that cannot be used to monitor quinine response in the regions of the Republic of Congo, where the isolates came from. This finding suggests that there exists a genetic background associated with geographic area for the association that will prevent the use of Pfnhe as a molecular marker for QNR. The contribution of Pfnhe to the in vitro response to quinine remains to be assessed in other regions, including in countries with different levels of drug pressure. PMID:21314947

  20. Propionate induces cell swelling and K+ accumulation in shark rectal gland

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Feldman, G.M.; Ziyadeh, F.N.; Mills, J.W.

    1989-08-01

    Small organic anions have been reported to induce cell solute accumulation and swelling. To investigate the mechanism of swelling, we utilized preparations of rectal gland cells from Squalus acanthias incubated in medium containing propionate. Propionate causes cells to swell by diffusing across membranes in its nonionic form, acidifying cell contents, and activating the Na+-H+ antiporter. The Na+-H+ exchange process tends to correct intracellular pH (pHi), and thus it maintains a favorable gradient for propionic acid diffusion and allows propionate to accumulate. Activation of the Na+-H+ antiport also facilitates Na+ entry into the cell and Nai accumulation. At the same timemore » Na+-K+-ATPase activity, unaffected by propionate, replaces Nai with Ki, whereas the K+ leak rate, decreased by propionate, allows Ki to accumulate. As judged by {sup 86}Rb+ efflux, the reduction in K+ leak was not due to propionate-induced cell acidification or reduction in Cli concentration. Despite inducing cell swelling, propionate did not disrupt cell structural elements and F actin distribution along cell membranes.« less

  1. Hydrogen Sulfide Attenuates the Recruitment of CD11b+Gr-1+ Myeloid Cells and Regulates Bax/Bcl-2 Signaling in Myocardial Ischemia Injury

    PubMed Central

    Zhang, Youen; Li, Hua; Zhao, Gang; Sun, Aijun; Zong, Nobel C.; Li, Zhaofeng; Zhu, Hongming; Zou, Yunzeng; Yang, Xiangdong; Ge, Junbo

    2014-01-01

    Hydrogen sulfide, an endogenous signaling molecule, plays an important role in the physiology and pathophysiology of the cardiovascular system. Using a mouse model of myocardial infarction, we investigated the anti-inflammatory and anti-apoptotic effects of the H2S donor sodium hydrosulfide (NaHS). The results demonstrated that the administration of NaHS improved survival, preserved left ventricular function, limited infarct size, and improved H2S levels in cardiac tissue to attenuate the recruitment of CD11b+Gr-1+ myeloid cells and to regulate the Bax/Bcl-2 pathway. Furthermore, the cardioprotective effects of NaHS were enhanced by inhibiting the migration of CD11b+Gr-1+ myeloid cells from the spleen into the blood and by attenuating post-infarction inflammation. These observations suggest that the novel mechanism underlying the cardioprotective function of H2S is secondary to a combination of attenuation the recruitment of CD11b+Gr-1+ myeloid cells and regulation of the Bax/Bcl-2 apoptotic signaling. PMID:24758901

  2. Depolarizing Actions of Hydrogen Sulfide on Hypothalamic Paraventricular Nucleus Neurons

    PubMed Central

    Khademullah, C. Sahara; Ferguson, Alastair V.

    2013-01-01

    Hydrogen sulfide (H2S) is a novel neurotransmitter that has been shown to influence cardiovascular functions as well and corticotrophin hormone (CRH) secretion. Since the paraventricular nucleus of the hypothalamus (PVN) is a central relay center for autonomic and endocrine functions, we sought to investigate the effects of H2S on the neuronal population of the PVN. Whole cell current clamp recordings were acquired from the PVN neurons and sodium hydrosulfide hydrate (NaHS) was bath applied at various concentrations (0.1, 1, 10, and 50 mM). NaHS (1, 10, and 50 mM) elicited a concentration-response relationship from the majority of recorded neurons, with almost exclusively depolarizing effects following administration. Cells responded and recovered from NaHS administration quickly and the effects were repeatable. Input differences from baseline and during the NaHS-induced depolarization uncovered a biphasic response, implicating both a potassium and non-selective cation conductance. The results from the neuronal population of the PVN shed light on the possible physiological role that H2S has in autonomic and endocrine function. PMID:23691233

  3. Adsorption of phenanthrene on activated carbon increases mineralization rate by specific bacteria.

    PubMed

    Leglize, Pierre; Alain, Saada; Jacques, Berthelin; Corinne, Leyval

    2008-03-01

    Bioavailability of polycyclic aromatic hydrocarbons (PAH) in soil is affected by PAH sorption to solid phase. We studied the influence of activated carbon (AC) on phenanthrene (PHE) mineralization by five degrading bacterial strains isolated from contaminated soil. PHE adsorption on AC was important and reduced PHE aqueous concentration up to 90%. PHE degradation was improved in the presence of activated carbon with three of the bacterial strains, named NAH1, MATE3 and MATE7, which produced biofilms, whereas it was not improved with the two other ones, which did not produce biofilms, MATE10 and MATE12. Monitoring PHE distribution during incubation showed that aqueous PHE concentration was significantly higher with the biofilm-producing NAH1 than with MATE10. Bacterial adhesion on AC was also investigated. The precoating of AC with PHE increased NAH1 and MATE3 adhesion to the solid surface (>16 and >13%, respectively). Bacterial properties, such as biofilm production and adhesion to AC capacity seemed to be related to their ability to optimize PHE degradation by improving PHE diffusion and reducing diffusion path length.

  4. Comparison of modal analysis results of laser vibrometry and nearfield acoustical holography measurements of an aluminum plate

    NASA Astrophysics Data System (ADS)

    Potter, Jennifer L.

    2011-12-01

    Noise and vibration has long been sought to be reduced in major industries: automotive, aerospace and marine to name a few. Products must be tested and pass certain levels of federally regulated standards before entering the market. Vibration measurements are commonly acquired using accelerometers; however limitations of this method create a need for alternative solutions. Two methods for non-contact vibration measurements are compared: Laser Vibrometry, which directly measures the surface velocity of the aluminum plate, and Nearfield Acoustic Holography (NAH), which measures sound pressure in the nearfield, and using Green's Functions, reconstructs the surface velocity at the plate. The surface velocity from each method is then used in modal analysis to determine the comparability of frequency, damping and mode shapes. Frequency and mode shapes are also compared to an FEA model. Laser Vibrometry is a proven, direct method for determining surface velocity and subsequently calculating modal analysis results. NAH is an effective method in locating noise sources, especially those that are not well separated spatially. Little work has been done in incorporating NAH into modal analysis.

  5. Intracellular pH regulation in hepatocytes isolated from three teleost species.

    PubMed

    Furimsky, M; Moon, T W; Perry, S F

    1999-09-01

    The mechanisms of intracellular pH (pH(i)) regulation were studied in hepatocytes isolated from three species of teleost: rainbow trout (Oncorhynchus mykiss), black bullhead (Ameiurus melas) and American eel (Anguilla rostrata). Intracellular pH was monitored over time using the pH-sensitive fluorescent dye BCECF in response to acid loading under control conditions and in different experimental media containing either low Na(+) or Cl(-) concentrations, the Na(+)-H(+) exchanger blocker amiloride or the blocker of the V-type H(+)-ATPase, bafilomycin A(1). In trout and bullhead hepatocytes, recovery to an intracellular acid load occurred principally by way of a Na(+)-dependent amiloride-sensitive Na(+)-H(+) exchanger. In eel hepatocytes, the Na(+)-H(+) exchanger did not contribute to recovery to an acid load though evidence suggests that it is present on the cell membrane and participates in the maintenance of steady-state pH(i). The V-type H(+)-ATPase did not participate in recovery to an acid load in any species. A Cl(-)-HCO(3)(-) exchanger may play a role in recovery to an acid load in eel hepatocytes by switching off and retaining base that would normally be tonically extruded. Thus, it is clear that hepatocytes isolated from the three species are capable of regulating pH(i), principally by way of a Na(+)-H(+) exchanger and a Cl(-)-HCO(3)(-) exchanger, but do not exploit identical mechanisms for pH(i) recovery. J. Exp. Zool. 284:361-367, 1999. Copyright 1999 Wiley-Liss, Inc.

  6. Patient-Reported Outcome questionnaires for hip arthroscopy: a systematic review of the psychometric evidence

    PubMed Central

    2011-01-01

    Background Hip arthroscopies are often used in the treatment of intra-articular hip injuries. Patient-reported outcomes (PRO) are an important parameter in evaluating treatment. It is unclear which PRO questionnaires are specifically available for hip arthroscopy patients. The aim of this systematic review was to investigate which PRO questionnaires are valid and reliable in the evaluation of patients undergoing hip arthroscopy. Methods A search was conducted in Pubmed, Medline, CINAHL, the Cochrane Library, Pedro, EMBASE and Web of Science from 1931 to October 2010. Studies assessing the quality of PRO questionnaires in the evaluation of patients undergoing hip arthroscopy were included. The quality of the questionnaires was evaluated by the psychometric properties of the outcome measures. The quality of the articles investigating the questionnaires was assessed by the COSMIN list. Results Five articles identified three questionnaires; the Modified Harris Hip Score (MHHS), the Nonarthritic Hip Score (NAHS) and the Hip Outcome Score (HOS). The NAHS scored best on the content validity, whereas the HOS scored best on agreement, internal consistency, reliability and responsiveness. The quality of the articles describing the HOS scored highest. The NAHS is the best quality questionnaire. The articles describing the HOS are the best quality articles. Conclusions This systematic review shows that there is no conclusive evidence for the use of a single patient-reported outcome questionnaire in the evaluation of patients undergoing hip arthroscopy. Based on available psychometric evidence we recommend using a combination of the NAHS and the HOS for patients undergoing hip arthroscopy. PMID:21619610

  7. Craniota, Wirbel- oder Schädeltiere

    NASA Astrophysics Data System (ADS)

    Schultze, Hans-Peter

    Zu den Craniota zählen alle Chordatiere, die eine dreiteilige Regionalisierung des Körpers in Kopf, Rumpf und Schwanz aufweisen. Der Kopf umfasst (1) das Neurocranium mit Gehirn und komplexen Sinnesorganen zur Wahrnehmung der Umgebung, (2) das Viscerocranium zur Nahrungsaufnahme und zur Ventilation der Kiemen bei den primär wasserlebenden Craniota und (3) das Dermatocranium (S. 38). Letzteres entsteht durch Verknöcherungen im Bindegewebe des Integuments, es dient dem Schutz des Kopfes und trägt im Mundbreich die Zähne. Zusammen bilden die drei Skelettstrukturen die funktionelle Einheit Schädel (Cranium). Außer der (somatischen) Rumpfmuskulatur und dem Axialskelett liegen im Rumpf Kreislauf-, Atmungs-, Verdauungs-, Exkretions- und Fortpflanzungsorgane. Der Schwanz, der Abschnitt hinter der Afteröffnung, die das Ende der Leibeshöhle markiert, dient mit Muskeln und Schwanzflosse der Fortbewegung.

  8. Interior near-field acoustical holography in flight.

    PubMed

    Williams, E G; Houston, B H; Herdic, P C; Raveendra, S T; Gardner, B

    2000-10-01

    In this paper boundary element methods (BEM) are mated with near-field acoustical holography (NAH) in order to determine the normal velocity over a large area of a fuselage of a turboprop airplane from a measurement of the pressure (hologram) on a concentric surface in the interior of the aircraft. This work represents the first time NAH has been applied in situ, in-flight. The normal fuselage velocity was successfully reconstructed at the blade passage frequency (BPF) of the propeller and its first two harmonics. This reconstructed velocity reveals structure-borne and airborne sound-transmission paths from the engine to the interior space.

  9. Exogenous hydrogen sulfide promotes hepatocellular carcinoma cell growth by activating the STAT3-COX-2 signaling pathway

    PubMed Central

    Zhen, Yulan; Wu, Qiaomei; Ding, Yiqian; Zhang, Wei; Zhai, Yuansheng; Lin, Xiaoxiong; Weng, Yunxia; Guo, Ruixian; Zhang, Ying; Feng, Jianqiang; Lei, Yiyan; Chen, Jingfu

    2018-01-01

    The effects of hydrogen sulfide (H2S) on cancer are controversial. Our group previously demonstrated that exogenous H2S promotes the development of cancer via amplifying the activation of the nuclear factor-κB signaling pathway in hepatocellular carcinoma (HCC) cells (PLC/PRF/5). The present study aimed to further investigate the hypothesis that exogenous H2S promotes PLC/PRF/5 cell proliferation and migration, and inhibits apoptosis by activating the signal transducer and activator of transcription 3 (STAT3)-cyclooxygenase-2 (COX-2) signaling pathway. PLC/PRF/5 cells were treated with 500 µmol/l NaHS (a donor of H2S) for 24 h. The expression levels of phosphorylated (p)-STAT3, STAT3, cleaved caspase-3 and COX-2 were measured by western blot assay. Cell viability was detected by Cell Counting kit-8 assay. Apoptotic cells were observed by Hoechst 33258 staining. The expression of STAT3 and COX-2 messenger RNA (mRNA) was detected by semiquantitative reverse transcription-polymerase chain reaction. The production of vascular endothelial growth factor (VEGF) was evaluated by ELISA. The results indicated that treatment of PLC/PRF/5 cells with 500 µmol/l NaHS for 24 h markedly increased the expression levels of p-STAT3 and STAT3 mRNA, leading to COX-2 and COX-2 mRNA overexpression, VEGF induction, decreased cleaved caspase-3 production, increased cell viability and migration, and decreased number of apoptotic cells. However, co-treatment of PLC/PRF/5 cells with 500 µmol/l NaHS and 30 µmol/l AG490 (an inhibitor of STAT3) or 20 µmol/l NS-398 (an inhibitor of COX-2) for 24 h significantly reverted the effects induced by NaHS. Furthermore, co-treatment of PLC/PRF/5 cells with 500 µmol/l NaHS and 30 µmol/l AG490 markedly decreased the NaHS-induced increase in the expression level of COX-2. By contrast, co-treatment of PLC/PRF/5 cells with 500 µmol/l NaHS and 20 µmol/l NS-398 inhibited the NaHS-induced increase in the expression level of p-STAT3. In conclusion, the

  10. [Sodium hydrosulfide improves cardiac functions and structures in rats with chronic heart failure].

    PubMed

    Li, Xiao-hui; Zhang, Chao-ying; Zhang, Ting

    2011-11-22

    To explore the effects of sodium hydrosulfide (NaHS), a hydrogen sulphide (H(2)S) donor, on cardiac functions and structures in rats with chronic heart failure induced by volume overload and examine its influence on cardiac remodelling. A total of 47 SD rats (120 - 140 g) were randomly divided into 5 groups:shunt group (n = 11), sham group (n = 8), shunt + NaHS group (n = 10), sham + NaHS group (n = 8) and shunt + phentolamine group (n = 10). The rat model of chronic heart failure was induced by abdominal aorta-inferior vena cava puncture. At Week 8 post-operation, hemodynamic parameters, microstructures and ultrastructures of myocardial tissues were analyzed. Extracellular collagen content in myocardial tissues was analyzed after Sirius red staining. Right ventricular hydroxyproline concentration was determined and compared. At Week 8 post-operation, compared with the sham operation and shunt + NaHS groups, the shunt group showed significantly increased right ventricular systolic pressure (RVSP) and right ventricular end diastolic pressure (RVEDP) (mm Hg: 35.2 ± 3.9 vs 21.4 ± 3.7 and 28.1 ± 2.7, 32 ± 5 vs 21 ± 4 and 26 ± 4, all P < 0.05, 1 mm Hg = 0.133 kPa). The RV peak rate of contraction and relaxation markedly decreased (RV ± dp/dt max) (mm Hg/s: 1528 ± 113 vs 2336 ± 185 and 1835 ± 132, 1331 ± 107 vs 2213 ± 212 and 1768 ± 116, all P < 0.05). It was found microscopically that myocardial fibers in the shunt group were irregularly arranged, partially cytolysis and infiltrated by inflammatory cells. Electron microscopy revealed that myocardial fibers thickened non-uniformly in the shunt group, some fiber mitochondria were highly swollen and contained vacuoles. And sarcoplasmic reticulum appeared slightly dilated. Polarized microscopy indicated that, collagen content (particularly type-I collagen) increased in the shunt group compared with the sham operation group. Additionally, compared with the shunt group, the shunt and NaHS treatment groups showed

  11. Elastolysen und Hauterkrankungen mit Verlust der elastischen Fasern.

    PubMed

    Tronnier, Michael

    2018-02-01

    Die elastischen Fasern sind neben den kollagenen Fasern der wichtigste Bestandteil des Bindegewebsgerüstes der Haut. Eine Verminderung oder ein Verlust der elastischen Fasern ist bei einer Vielzahl von klinisch sich unterschiedlich präsentierenden Erkrankungen, hereditär oder erworben, beschrieben. Bei den Erkrankungen, die mit einer Entzündung einhergehen ist die Elastophagozytose ein wichtiges histologisches Merkmal. Die Therapie der Erkrankungen dieser Gruppe ist grundsätzlich schwierig. © 2018 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

  12. Supply Chain Management (SCM) mit Kanban

    NASA Astrophysics Data System (ADS)

    Beer, Anja; Dickmann, Eva; Dickmann, Philipp; Gerth, Wolf-Michael; Graßy, Mario; Herron, Colin; Schmidt, Peter; Seidl, Florian; Wittmann, Claus-Eduard

    Nach Schätzungen von Mercer Management Consulting und dem Fraunhofer Institut wird der Wertschöpfungsanteil in der Automobilindustrie von durchschnittlich 35 % im Jahr 2002 auf 23 % im Jahr 2015 sinken [Merc 04]. Der Trend, die Produktionstiefe oder allgemeiner, die Wertschöpfungstiefe, zu reduzieren, hat zur Folge, dass die Kaufteile den größeren Teil der Wertschöpfung einnehmen. Die Optimierungspotentiale und der Einfluss auf die Kosten wandern immer mehr zu den Lieferanten, vor allem bei größeren Unternehmen oder Konzernen. Lieferanten-Philosophien, die auf oberflächlichen Verbindungen zu Lieferanten aufbauen, um immer optimal und schnell den günstigsten Teilepreis zu erhalten, haben sich in vielen Sparten oder Produktbereichen, z. B. im Maschinenbau, im besten Fall als kurzfristig erfolgreich erwiesen. Kooperative und nachhaltige Strategien sind der erfolgversprechendere Weg, zumindest mittelbis langfristig. In der Realität wird sehr wenig in Supply Chain-Konzepte investiert und die Umsetzungen sind daher vielmals oberflächlich.

  13. Cross-talk between hydrogen sulfide and carbon monoxide in the mechanism of experimental gastric ulcers healing, regulation of gastric blood flow and accompanying inflammation.

    PubMed

    Magierowski, Marcin; Magierowska, Katarzyna; Hubalewska-Mazgaj, Magdalena; Surmiak, Marcin; Sliwowski, Zbigniew; Wierdak, Mateusz; Kwiecien, Slawomir; Chmura, Anna; Brzozowski, Tomasz

    2018-03-01

    Hydrogen sulfide (H 2 S) and carbon monoxide (CO) exert gastroprotection against acute gastric lesions. We determined the cross-talk between H 2 S and CO in gastric ulcer healing process and regulation of gastric blood flow (GBF) at ulcer margin. Male Wistar rats with acetic acid-induced gastric ulcers were treated i.g. throughout 9 days with vehicle (control), NaHS (0.1-10 mg/kg) +/- zinc protoporphyrin (ZnPP, 10 mg/kg), d,l-propargylglycine (PAG, 30 mg/kg), CO-releasing CORM-2 (2.5 mg/kg) +/- PAG. GBF was assessed by laser flowmetry, ulcer area was determined by planimetry/histology. Gastric mucosal H 2 S production was analysed spectrophotometrically. Protein and/or mRNA expression at ulcer margin for vascular endothelial growth factor (VEGF)A, epidermal growth factor receptor (EGFr), cystathionine-γ-lyase (CSE), cystathionine-β-synthase (CBS), 3-mercaptopyruvate sulfurtransferase (3-MST), heme oxygenases (HOs), nuclear factor (erythroid-derived 2)-like 2 (Nrf-2), cyclooxygenase (COX)-2, inducible nitric oxide synthase (iNOS), IL-1β, TNF-α and hypoxia inducible factor (HIF)-1α were determined by real-time PCR or western blot. IL-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, IL-13, IFN-γ, TNF-α, GM-CSF plasma concentration was assessed using Luminex platform. NaHS dose-dependently decreased ulcer area and increased GBF but ZnPP attenuated these effects. PAG decreased H 2 S production but failed to affect CORM-2-mediated ulcer healing and vasodilation. NaHS increased Nrf-2, EGFr, VEGFA and decreased pro-inflammatory markers expression and IL-1β, IL-2, IL-13, TNF-α, GM-CSF plasma concentration. CORM-2 decreased IL-1β and GM-CSF plasma levels. We conclude that NaHS accelerates gastric ulcer healing increasing microcirculation and Nrf-2, EGFr, VEGFA expression. H 2 S-mediated ulcer healing involves endogenous CO activity while CO does not require H 2 S. NaHS decreases systemic inflammation more effectively than CORM-2. Copyright © 2017

  14. Crystal Structures of Apo and Liganded 4-Oxalocrotonate Decarboxylase Uncover a Structural Basis for the Metal-Assisted Decarboxylation of a Vinylogous β-Keto Acid.

    PubMed

    Guimarães, Samuel L; Coitinho, Juliana B; Costa, Débora M A; Araújo, Simara S; Whitman, Christian P; Nagem, Ronaldo A P

    2016-05-10

    The enzymes in the catechol meta-fission pathway have been studied for more than 50 years in several species of bacteria capable of degrading a number of aromatic compounds. In a related pathway, naphthalene, a toxic polycyclic aromatic hydrocarbon, is fully degraded to intermediates of the tricarboxylic acid cycle by the soil bacteria Pseudomonas putida G7. In this organism, the 83 kb NAH7 plasmid carries several genes involved in this biotransformation process. One enzyme in this route, NahK, a 4-oxalocrotonate decarboxylase (4-OD), converts 2-oxo-3-hexenedioate to 2-hydroxy-2,4-pentadienoate using Mg(2+) as a cofactor. Efforts to study how 4-OD catalyzes this decarboxylation have been hampered because 4-OD is present in a complex with vinylpyruvate hydratase (VPH), which is the next enzyme in the same pathway. For the first time, a monomeric, stable, and active 4-OD has been expressed and purified in the absence of VPH. Crystal structures for NahK in the apo form and bonded with five substrate analogues were obtained using two distinct crystallization conditions. Analysis of the crystal structures implicates a lid domain in substrate binding and suggests roles for specific residues in a proposed reaction mechanism. In addition, we assign a possible function for the NahK N-terminal domain, which differs from most of the other members of the fumarylacetoacetate hydrolase superfamily. Although the structural basis for metal-dependent β-keto acid decarboxylases has been reported, this is the first structural report for that of a vinylogous β-keto acid decarboxylase and the first crystal structure of a 4-OD.

  15. Exogenous hydrogen sulfide exerts proliferation, anti-apoptosis, migration effects and accelerates cell cycle progression in multiple myeloma cells via activating the Akt pathway.

    PubMed

    Zheng, Dong; Chen, Ziang; Chen, Jingfu; Zhuang, Xiaomin; Feng, Jianqiang; Li, Juan

    2016-10-01

    Hydrogen sulfide (H2S), regarded as the third gaseous transmitter, mediates and induces various biological effects. The present study investigated the effects of H2S on multiple myeloma cell progression via amplifying the activation of Akt pathway in multiple myeloma cells. The level of H2S produced in multiple myeloma (MM) patients and healthy subjects was measured using enzyme-linked immunosorbent assay (ELISA). MM cells were treated with 500 µmol/l NaHS (a donor of H2S) for 24 h. The expression levels of phosphorylated-Akt (p-Akt), Bcl-2 and caspase-3 were measured by western blot assay. Cell viability was detected by Cell Counting Kit 8 (CCK-8). The cell cycle was analyzed by flow cytometry. Our results show that the concentration of H2S was higher in MM patients and that it increased in parallel with disease progression. Treating MM cells with 500 µmol/l NaHS for 24 h markedly increased the expression level of Bcl-2 and the activation of p-Akt, however, the expression level of caspase-3 was decreased, cell viability was increased, and cell cycle progression was accelerated in MM cells. NaHS also induced migration in MM cells in transwell migration assay. Furthermore, co-treatment of MM cells with 500 µmol/l NaHS and 50 µmol/l LY294002 for 24 h significantly overset these effects. In conclusion, our findings demonstrate that the Akt pathway contributes to NaHS-induced cell proliferation, migration and acceleration of cell cycle progression in MM cells.

  16. Strategy of Pseudomonas pseudoalcaligenes C70 for effective degradation of phenol and salicylate

    PubMed Central

    Heinaru, Eeva; Naanuri, Eve; Mehike, Maris; Leito, Ivo; Heinaru, Ain

    2017-01-01

    Phenol- and naphthalene-degrading indigenous Pseudomonas pseudoalcaligenes strain C70 has great potential for the bioremediation of polluted areas. It harbours two chromosomally located catechol meta pathways, one of which is structurally and phylogenetically very similar to the Pseudomonas sp. CF600 dmp operon and the other to the P. stutzeri AN10 nah lower operon. The key enzymes of the catechol meta pathway, catechol 2,3-dioxygenase (C23O) from strain C70, PheB and NahH, have an amino acid identity of 85%. The metabolic and regulatory phenotypes of the wild-type and the mutant strain C70ΔpheB lacking pheB were evaluated. qRT-PCR data showed that in C70, the expression of pheB- and nahH-encoded C23O was induced by phenol and salicylate, respectively. We demonstrate that strain C70 is more effective in the degradation of phenol and salicylate, especially at higher substrate concentrations, when these compounds are present as a mixture; i.e., when both pathways are expressed. Moreover, NahH is able to substitute for the deleted PheB in phenol degradation when salicylate is also present in the growth medium. The appearance of a yellow intermediate 2-hydroxymuconic semialdehyde was followed by the accumulation of catechol in salicylate-containing growth medium, and lower expression levels and specific activities of the C23O of the sal operon were detected. However, the excretion of the toxic intermediate catechol to the growth medium was avoided when the growth medium was supplemented with phenol, seemingly due to the contribution of the second meta pathway encoded by the phe genes. PMID:28257519

  17. Studies on the mechanisms underlying amiloride enhancement of 3,4-methylenedioxymethamphetamine-induced serotonin depletion in rats.

    PubMed

    Goñi-Allo, Beatriz; Puerta, Elena; Hervias, Isabel; Di Palma, Richard; Ramos, Maria; Lasheras, Berta; Aguirre, Norberto

    2007-05-21

    Amiloride and several of its congeners known to block the Na(+)/Ca(2+) and/or Na(+)/H(+) antiporters potentiate methamphetamine-induced neurotoxicity without altering methamphetamine-induced hyperthermia. We now examine whether amiloride also exacerbates 3,4-methylenedioxymethamphetamine (MDMA)-induced long-term serotonin (5-HT) loss in rats. Amiloride (2.5 mg/kg, every 2 h x 3, i.p.) given at ambient temperature 30 min before MDMA (5 mg/kg, every 2 h x 3, i.p.), markedly exacerbated long-term 5-HT loss. However, in contrast to methamphetamine, amiloride also potentiated MDMA-induced hyperthermia. Fluoxetine (10 mg/kg i.p.) completely protected against 5-HT depletion caused by the MDMA/amiloride combination without significantly altering the hyperthermic response. By contrast, the calcium channel antagonists flunarizine or diltiazem did not afford any protection. Findings with MDMA and amiloride were extended to the highly selective Na(+)/H(+) exchange inhibitor dimethylamiloride, suggesting that the potentiating effects of amiloride are probably mediated by the blockade of Na(+)/H(+) exchange. When the MDMA/amiloride combination was administered at 15 degrees C hyperthermia did not develop and brain 5-HT concentrations remained unchanged 7 days later. Intrastriatal perfusion of MDMA (100 microM for 8 h) in combination with systemic amiloride caused a small depletion of striatal 5-HT content in animals made hyperthermic but not in the striatum of normothermic rats. These data suggest that enhancement of MDMA-induced 5-HT loss caused by amiloride or dimethylamiloride depends on their ability to enhance MDMA-induced hyperthermia. We hypothesise that blockade of Na(+)/H(+) exchange could synergize with hyperthermia to render 5-HT terminals more vulnerable to the toxic effects of MDMA.

  18. Hydrogen Sulfide Suppresses Oxidized Low-density Lipoprotein (Ox-LDL)-stimulated Monocyte Chemoattractant Protein 1 generation from Macrophages via the Nuclear Factor κB (NF-κB) Pathway*

    PubMed Central

    Du, Junbao; Huang, Yaqian; Yan, Hui; Zhang, Qiaoli; Zhao, Manman; Zhu, Mingzhu; Liu, Jia; Chen, Stella X.; Bu, Dingfang; Tang, Chaoshu; Jin, Hongfang

    2014-01-01

    This study was designed to examine the role of hydrogen sulfide (H2S) in the generation of oxidized low-density lipoprotein (ox-LDL)-stimulated monocyte chemoattractant protein 1 (MCP-1) from macrophages and possible mechanisms. THP-1 cells and RAW macrophages were pretreated with sodium hydrosulfide (NaHS) and hexyl acrylate and then treated with ox-LDL. The results showed that ox-LDL treatment down-regulated the H2S/cystathionine-β-synthase pathway, with increased MCP-1 protein and mRNA expression in both THP-1 cells and RAW macrophages. Hexyl acrylate promoted ox-LDL-induced inflammation, whereas the H2S donor NaHS inhibited it. NaHS markedly suppressed NF-κB p65 phosphorylation, nuclear translocation, DNA binding activity, and recruitment to the MCP-1 promoter in ox-LDL-treated macrophages. Furthermore, NaHS decreased the ratio of free thiol groups in p65, whereas the thiol reductant DTT reversed the inhibiting effect of H2S on the p65 DNA binding activity. Most importantly, site-specific mutation of cysteine 38 to serine in p65 abolished the effect of H2S on the sulfhydration of NF-κB and ox-LDL-induced NF-κB activation. These results suggested that endogenous H2S inhibited ox-LDL-induced macrophage inflammation by suppressing NF-κB p65 phosphorylation, nuclear translocation, DNA binding activity, and recruitment to the MCP-1 promoter. The sulfhydration of free thiol group on cysteine 38 in p65 served as a molecular mechanism by which H2S inhibited NF-κB pathway activation in ox-LDL-induced macrophage inflammation. PMID:24550391

  19. Increased Endothelin Activity Mediates Augmented Distal Nephron Acidification Induced by Dietary Protein

    PubMed Central

    Khanna, Apurv; Simoni, Jan; Hacker, Callenda; Duran, Marie-Josée; Wesson, Donald E

    2005-01-01

    We tested the hypothesis that increased dietary protein augments distal nephron acidification through an endothelin-dependent mechanism. Munich-Wistar rats ate minimum electrolyte diets of 50% (HiPro) and 20% (CON) casein-provided protein, the latter comparable to standard chow. HiPro vs. CON had higher distal nephron H+ secretion (41.3 ± 4.0 vs. 23.0 ± 2.1 pmol/mm.min, p < 0.002) mediated by augmented Na+/H+ exchange and H+-ATPase activity. Renal cortex of HiPro vs. CON had higher ET-1 addition to microdialysate and higher ET-1 mRNA, consistent with increased renal ET-1 production. Bosentan, an endothelin A/B receptor antagonist, decreased HiPro distal nephron H+ secretion (28.4 ± 2.4 vs. 41.3 ± 4.0 pmol/mm.min, p < 0.016) through decreased Na+/H+ exchange and decreased H+-ATPase activity. Increased dietary protein augments distal nephron acidification through an endothelin-sensitive increase in Na+/H+ exchange and H+-ATPase activity, supporting an endothelin role in the distal nephron response to this common challenge to acid-base status. PMID:16555618

  20. Grundlagen des Tissue Engineering

    NASA Astrophysics Data System (ADS)

    Mayer, Jörg; Blum, Janaki; Wintermantel, Erich

    Die Organtransplantation stellt eine verbreitete Therapie dar, um bei krankheitsoder unfallbedingter Schädigung eines Organs die Gesamtheit seiner Funktionen wieder herzustellen, indem es durch ein Spenderorgan ersetzt wird. Organtransplantationen werden für die Leber, die Niere, die Lunge, das Herz oder bei schweren grossflächigen Verbrennungen der Haut vorgenommen. Der grosse apparative, personelle und logistische Aufwand und die Risiken der Transplantationschirurgie (Abstossungsreaktionen) sowie die mangelnde Verfügbarkeit von immunologisch kompatiblen Spenderorganen führen jedoch dazu, dass der Bedarf an Organtransplantaten nur zu einem sehr geringen Teil gedeckt werden kann. Sind Spenderorgane nicht verfügbar, können in einzelnen Fällen lebenswichtige Teilfunktionen, wie beispielsweise die Filtrationsfunktion der Niere durch die Blutreinigung mittels Dialyse ersetzt oder, bei mangelnder Funktion der Bauchspeicheldrüse (Diabetes), durch die Verabreichung von Insulin ein normaler Zustand des Gesamtorganismus auch über Jahre hinweg erhalten werden. Bei der notwendigen lebenslangen Anwendung apparativer oder medikamentöser Therapie können für den Patienten jedoch häufig schwerwiegende, möglicherweise lebensverkürzende Nebenwirkungen entstehen. Daher werden in der Forschung Alternativen gesucht, um die Funktionen des ausgefallenen Organs durch die Implantation von Zellen oder in vitro gezüchteten Geweben möglichst umfassend wieder herzustellen. Dies erfordert biologisch aktive Implantate, welche die für den Stoffwechsel des Organs wichtigen Zellen enthalten und einen organtypischen Stoffwechsel entfalten.

  1. Significance of hydrogen sulfide in sepsis-induced myocardial injury in rats

    PubMed Central

    Li, Xiaoqing; Cheng, Qinghong; Li, Jianhua; He, Yonglai; Tian, Peigang; Xu, Chao

    2017-01-01

    Sepsis-induced myocardial injury is a detrimental disorder for intensive care medicine due to its high rates of morbidity and mortality. Data suggest that nuclear factor (NF)-κB serves a critical role in the pathogenesis of myocardial injury. Hydrogen sulfide (H2S) serves an important role in the physiology and pathophysiology of regulatory mechanisms, particularly during an inflammatory reaction. However, the relationship between NF-κB and H2S in sepsis-induced myocardial injury is not well understood, and the underlying mechanisms remain unclear. In the present study, 60 male Sprague Dawley rats were randomly divided into the following six groups: A sham group, cecal ligation and puncture (CLP) group, sham + propargylglycine (PAG) group, CLP + PAG group, sham + sodium hydrosulfide (NaHS) group and CLP + NaHS group, with 10 rats in each group. The rats in all groups were sacrificed 12 h after surgery for sample collection. Compared with the sham group, it was observed that the concentrations of Creatine Kinase-MB (CK-MB) and cardiac troponin I (cTnI) in the serum, and pathological scores of myocardial tissue were significantly increased in the CLP, CLP + NaHS and CLP + PAG groups (P<0.05). The pathological scores and concentrations of CK-MB and cTnI were significantly higher in the CLP + PAG group (P<0.05) and significantly lower in the CLP + NaHS group (P<0.05) when compared with the CLP group. The expression of cystathionine-γ-lyase (CSE) mRNA and content of interleukin (IL)-10 were significantly higher in the CLP group compared with the CLP + PAG group (P<0.05), while the expression of myocardial NF-κB and content of tumor necrosis factor (TNF)-α in the CLP group were significantly lowered compared with the CLP + PAG group (P<0.05). The expression of NF-κB and content of TNF-α were significantly increased in the CLP group when compared with the CLP + NaHS group (P<0.05), while the content of myocardial IL-10 in the CLP group was significantly lower than

  2. Funkmesstechnik

    NASA Astrophysics Data System (ADS)

    Plaßmann, Wilfried

    Ein Hauptgebiet der Funkmesstechnik ist durch den Begriff RADAR (radio detection and ranging gekennzeichnet. Bei diesem Verfahren werden impulsförmige elektromagnetische Wellen von einer Antenne ausgesendet und an Körpern oder Stoffverteilungen (Wolken) reflektiert. Die Sendeantenne wird auf Empfang umgeschaltet, und anhand des Echos sind Rückschlüsse auf die Lage und die Beschaffenheit der Körper oder der Stoffverteilungen möglich. Angewendet wird die Radartechnik bei der Kontrolle und der Sicherung des Land-, Wasser- und Flugverkehrs, in der Meteorologie zur Wetterprognose, in der Astrologie und im militärischen Bereich.

  3. Inhibition of Hydrogen Sulfide-induced Angiogenesis and Inflammation in Vascular Endothelial Cells: Potential Mechanisms of Gastric Cancer Prevention by Korean Red Ginseng.

    PubMed

    Choi, Ki-Seok; Song, Heup; Kim, Eun-Hee; Choi, Jae Hyung; Hong, Hua; Han, Young-Min; Hahm, Ki Baik

    2012-04-01

    Previously, we reported that Helicobacter pylori-associated gastritis and gastric cancer are closely associated with increased levels of hydrogen sulfide (H2S) and that Korean red ginseng significantly reduced the severity of H. pylori-associated gastric diseases by attenuating H2S generation. Because the incubation of endothelial cells with H2S has been known to enhance their angiogenic activities, we hypothesized that the amelioration of H2S-induced gastric inflammation or angiogenesis in human umbilical vascular endothelial cells (HUVECs) might explain the preventive effect of Korean red ginseng on H. pylori-associated carcinogenesis. The expression of inflammatory mediators, angiogenic growth factors, and angiogenic activities in the absence or presence of Korean red ginseng extracts (KRGE) were evaluated in HUVECs stimulated with the H2S generator sodium hydrogen sulfide (NaHS). KRGE efficiently decreased the expression of cystathionine β-synthase and cystathionine γ-lyase, enzymes that are essential for H2S synthesis. Concomitantly, a significant decrease in the expression of inflammatory mediators, including cyclooxygenase-2 and inducible nitric oxide synthase, and several angiogenic factors, including interleukin (IL)-8, hypoxia inducible factor-1a, vascular endothelial growth factor, IL-6, and matrix metalloproteinases, was observed; all of these factors are normally induced after NaHS. An in vitro angiogenesis assay demonstrated that NaHS significantly increased tube formation in endothelial cells, whereas KRGE pretreatment significantly attenuated tube formation. NaHS activated p38 and Akt, increasing the expression of angiogenic factors and the proliferation of HUVECs, whereas KRGE effectively abrogated this H2S-activated angiogenesis and the increase in inflammatory mediators in vascular endothelial cells. In conclusion, KRGE was able to mitigate H2S-induced angiogenesis, implying that antagonistic action against H2S-induced angiogenesis may be the

  4. Hydrogen Sulfide Attenuates Neurodegeneration and Neurovascular Dysfunction Induced by Intracerebral Administered Homocysteine in Mice

    PubMed Central

    Kamat, Pradip K.; Kalani, Anuradha; Givvimani, Srikanth; Sathnur, PB; Tyagi, Suresh C.; Tyagi, Neetu

    2014-01-01

    High levels of homocysteine (Hcy), known as hyperhomocysteinemia (HHcy) are associated with neurovascular diseases. H2S, a metabolite of Hcy, has a potent anti-oxidant and anti-inflammatory activity; however, the effect of H2S has not been explored in Hcy (IC) induced neurodegeneration and neurovascular dysfunction in mice. Therefore, the present study was designed to explore the neuroprotective role of H2S on Hcy induced neurodegeneration and neurovascular dysfunction. To test this hypothesis we employed wild type (WT) males ages 8–10 weeks, WT+ artificial cerebrospinal fluid (aCSF), WT+ Hcy (0.5μmol/μl) intracerebral injection (I.C., one time only prior to NaHS treatment), WT+Hcy +NaHS (sodium hydrogen sulfide, precursor of H2S, 30 μmol/kg, body weight). NaHS was injected intra-peritoneally (I.P.) once daily for the period of 7 days after the Hcy (IC) injection. Hcy treatment significantly increased MDA, nitrite level, acetylcholinestrase activity, TNFα, IL1β, GFAP, iNOS, eNOS and decreased glutathione level indicating oxidative-nitrosative stress and neuroinflammation as compared to control and aCSF treated groups. Further, increased expression of NSE, S100B and decreased expression of (PSD95, SAP97) synaptic protein indicated neurodegeneration. Brain sections of Hcy treated mice showed damage in the cortical area and periventricular cells. TUNEL positive cells and Fluro Jade-C staining indicated apoptosis and neurodegeneration. The increased expression of MMP9, MMP2 and decreased expression of TIMP-1, TIMP-2, tight junction proteins (ZO1, Occuldin) in Hcy treated group indicate neurovascular remodeling. Interestingly, NaHS treatment significantly attenuated Hcy induced oxidative stress, memory deficit, neurodegeneration, neuroinflammation and cerebrovascular remodeling. The results indicate that H2S is effective in providing protection against neurodegeneration and neurovascular dysfunction. PMID:23912038

  5. Weight gain in Turner Syndrome: association to puberty induction? - longitudinal analysis of KIGS data.

    PubMed

    Reinehr, Thomas; Lindberg, Anders; Toschke, Christina; Cara, Jose; Chrysis, Dionisis; Camacho-Hübner, Cecilia

    2016-07-01

    Girls with Turner Syndrome (TS) treated or not treated with growth hormone (GH) are prone to overweight. Therefore, we hypothesize that puberty induction in TS is associated with weight gain. We analyzed weight changes (BMI-SDS) between onset of GH treatment and near adult height (NAH) in 887 girls with TS enrolled in KIGS (Pfizer International Growth Database). Puberty was induced with estrogens in 646 (72·8%) girls with TS. Weight status did not change significantly between GH treatment start and 1 year later (mean difference -0·02 BMI-SDS), but increased significantly (P < 0·001) until NAH (+0·40 BMI-SDS). The BMI-SDS increased +0·21 until start of puberty (P < 0·001). Girls with spontaneous and induced puberty showed similar BMI-SDS changes. Puberty induction at ≥12 years was associated with a significant (P < 0·001) less increase of BMI-SDS (+0·7 BMI-SDS) between baseline and NAH compared to puberty induction at <12 year (+1·0 BMI-SDS). In multiple linear regression analyses changes of BMI-SDS between baseline and NAH were negatively associated with baseline BMI-SDS (P < 0·001), GH doses (P = 0·015), and age at puberty induction (P < 0·001), positively with years on GH treatment (P = 0·004), while duration and dose of estrogens, its route of administration (transdermal/oral), changes of height-SDS, thyroxin and oxandrolone treatment, and karyotype did not correlate significantly to changes of BMI-SDS in this time period. Puberty does not seem to play a major role in weight gain in girls with TS since the majority of the increases in BMI-SDS occurred before puberty. However, late puberty induction seems to decrease the risk of weight gain. © 2016 John Wiley & Sons Ltd.

  6. Hydrogen sulfide attenuates carbon tetrachloride-induced hepatotoxicity, liver cirrhosis and portal hypertension in rats.

    PubMed

    Tan, Gang; Pan, Shangha; Li, Jie; Dong, Xuesong; Kang, Kai; Zhao, Mingyan; Jiang, Xian; Kanwar, Jagat R; Qiao, Haiquan; Jiang, Hongchi; Sun, Xueying

    2011-01-01

    Hydrogen sulfide (H(2)S) displays vasodilative, anti-oxidative, anti-inflammatory and cytoprotective activities. Impaired production of H(2)S contributes to the increased intrahepatic resistance in cirrhotic livers. The study aimed to investigate the roles of H(2)S in carbon tetrachloride (CCl(4))-induced hepatotoxicity, cirrhosis and portal hypertension. Sodium hydrosulfide (NaHS), a donor of H(2)S, and DL-propargylglycine (PAG), an irreversible inhibitor of cystathionine γ-lyase (CSE), were applied to the rats to investigate the effects of H(2)S on CCl(4)-induced acute hepatotoxicity, cirrhosis and portal hypertension by measuring serum levels of H(2)S, hepatic H(2)S producing activity and CSE expression, liver function, activity of cytochrome P450 (CYP) 2E1, oxidative and inflammatory parameters, liver fibrosis and portal pressure. CCl(4) significantly reduced serum levels of H(2)S, hepatic H(2)S production and CSE expression. NaHS attenuated CCl(4)-induced acute hepatotoxicity by supplementing exogenous H(2)S, which displayed anti-oxidative activities and inhibited the CYP2E1 activity. NaHS protected liver function, attenuated liver fibrosis, inhibited inflammation, and reduced the portal pressure, evidenced by the alterations of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), hyaluronic acid (HA), albumin, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6 and soluble intercellular adhesion molecule (ICAM)-1, liver histology, hepatic hydroxyproline content and α-smooth muscle actin (SMA) expression. PAG showed opposing effects to NaHS on most of the above parameters. Exogenous H(2)S attenuates CCl(4)-induced hepatotoxicity, liver cirrhosis and portal hypertension by its multiple functions including anti-oxidation, anti-inflammation, cytoprotection and anti-fibrosis, indicating that targeting H(2)S may present a promising approach, particularly for its prophylactic effects, against liver cirrhosis and portal hypertension.

  7. Effect of TPA on ion fluxes and DNA synthesis in vascular smooth muscle cells

    PubMed Central

    1985-01-01

    Previous reports have suggested that phorbol esters can decrease the affinity of epidermal growth factor (EGF) for its cellular receptors. Investigations of the consequences of the interaction between phorbol esters and EGF, however, have been limited to EGF-stimulated Na/H exchange in A431 cells (Whitely, B., D. Cassel, Y.-X. Zuang, and L. Glaser, 1984, J. Cell Biol., 99:1162-1166). In the present study, the effect of the phorbol ester 12-O-tetradecanoyl phorbol-13-acetate (TPA) on EGF-stimulated ion transport and DNA synthesis was determined in cultured vascular smooth muscle cells (A7r5). It was found that TPA stimulated Na/H exchange when added alone (half-maximal stimulatory concentration, 25 nM). However, when cells were pretreated with TPA and then challenged with EGF, TPA significantly inhibited EGF-stimulated Na/H exchange (78%; half-maximal inhibition [Ki] at 2.5 nM). Subsequently the effects of TPA on Na/K/Cl co-transport were measured. TPA was observed to inhibit Na/K/Cl co-transport (half-maximal inhibitory concentration, 50 nM) and also to inhibit EGF-stimulated Na/K/Cl co-transport (100%; Ki at 5 nM). Finally, the effects of TPA on DNA synthesis were assessed. TPA had a modest stimulatory effect on DNA synthesis (half-maximal stimulatory concentration, 6 nM), but had a significant inhibitory effect on EGF-stimulated DNA synthesis (56%; Ki at 5 nM). These findings suggest that the inhibitory effect of TPA on EGF-receptor functions goes beyond previously reported effects on Na/H exchange in A431 cells and extends to EGF-stimulation of Na/K/Cl co- transport and DNA synthesis in vascular smooth muscle cells. PMID:2410432

  8. Hydrogen Sulfide Alleviates Aluminum Toxicity via Decreasing Apoplast and Symplast Al Contents in Rice

    PubMed Central

    Zhu, Chun Q.; Zhang, Jun H.; Sun, Li M.; Zhu, Lian F.; Abliz, Buhailiqem; Hu, Wen J.; Zhong, Chu; Bai, Zhi G.; Sajid, Hussain; Cao, Xiao C.; Jin, Qian Y.

    2018-01-01

    Hydrogen sulfide (H2S) plays a vital role in Al3+ stress resistance in plants, but the underlying mechanism is unclear. In the present study, pretreatment with 2 μM of the H2S donor NaHS significantly alleviated the inhibition of root elongation caused by Al toxicity in rice roots, which was accompanied by a decrease in Al contents in root tips under 50 μM Al3+ treatment. NaHS pretreatment decreased the negative charge in cell walls by reducing the activity of pectin methylesterase and decreasing the pectin and hemicellulose contents in rice roots. This treatment also masked Al-binding sites in the cell wall by upregulating the expression of OsSATR1 and OsSTAR2 in roots and reduced Al binding in the cell wall by stimulating the expression of the citrate acid exudation gene OsFRDL4 and increasing the secretion of citrate acid. In addition, NaHS pretreatment decreased the symplasmic Al content by downregulating the expression of OsNRAT1, and increasing the translocation of cytoplasmic Al to the vacuole via upregulating the expression of OsALS1. The increment of antioxidant enzyme [superoxide dismutase (SOD), ascorbate peroxidase (APX), catalase (CAT), and peroxidase (POD)] activity with NaHS pretreatment significantly decreased the MDA and H2O2 content in rice roots, thereby reducing the damage of Al3+ toxicity on membrane integrity in rice. H2S exhibits crosstalk with nitric oxide (NO) in response to Al toxicity, and through reducing NO content in root tips to alleviate Al toxicity. Together, this study establishes that H2S alleviates Al toxicity by decreasing the Al content in the apoplast and symplast of rice roots. PMID:29559992

  9. Exogenous H2S facilitating ubiquitin aggregates clearance via autophagy attenuates type 2 diabetes-induced cardiomyopathy

    PubMed Central

    Wu, Jichao; Tian, Zhiliang; Sun, Yu; Lu, Cuicui; Liu, Ning; Gao, Zhaopeng; Zhang, Linxue; Dong, Shiyun; Yang, Fan; Zhong, Xin; Xu, Changqing; Lu, Fanghao; Zhang, Weihua

    2017-01-01

    Diabetic cardiomyopathy (DCM) is a serious complication of diabetes. Hydrogen sulphide (H2S), a newly found gaseous signalling molecule, has an important role in many regulatory functions. The purpose of this study is to investigate the effects of exogenous H2S on autophagy and its possible mechanism in DCM induced by type II diabetes (T2DCM). In this study, we found that sodium hydrosulphide (NaHS) attenuated the augment in left ventricular (LV) mass and increased LV volume, decreased reactive oxygen species (ROS) production and ameliorated H2S production in the hearts of db/db mice. NaHS facilitated autophagosome content degradation, reduced the expression of P62 (a known substrate of autophagy) and increased the expression of microtubule-associated protein 1 light chain 3 II. It also increased the expression of autophagy-related protein 7 (ATG7) and Beclin1 in db/db mouse hearts. NaHS increased the expression of Kelch-like ECH-associated protein 1 (Keap-1) and reduced the ubiquitylation level in the hearts of db/db mice. 1,4-Dithiothreitol, an inhibitor of disulphide bonds, increased the ubiquitylation level of Keap-1, suppressed the expression of Keap-1 and abolished the effects of NaHS on ubiquitin aggregate clearance and ROS production in H9C2 cells treated with high glucose and palmitate. Overall, we concluded that exogenous H2S promoted ubiquitin aggregate clearance via autophagy, which might exert its antioxidative effect in db/db mouse myocardia. Moreover, exogenous H2S increased Keap-1 expression by suppressing its ubiquitylation, which might have an important role in ubiquitin aggregate clearance via autophagy. Our findings provide new insight into the mechanisms responsible for the antioxidative effects of H2S in the context of T2DCM. PMID:28796243

  10. A salting out system for improving the efficiency of the headspace solid-phase microextraction of short and medium chain free fatty acids.

    PubMed

    Fiorini, Dennis; Pacetti, Deborah; Gabbianelli, Rosita; Gabrielli, Serena; Ballini, Roberto

    2015-08-28

    Given the importance of short and medium chain free fatty acids (FFAs) in several fields, this study sought to improve the extraction efficiency of the solid-phase microextraction (SPME) of FFAs by evaluating salting out agents that appear promising for this application. The salts ammonium sulfate ((NH4)2SO4) and sodium dihydrogen phosphate (NaH2PO4) were tried on their own and in combination (3.7/1), in four different total amounts, as salting out agents in the headspace-SPME-gas chromatographic (HS-SPME-GC) analysis of the FFAs from acetic acid (C2) to decanoic acid (C10). Their performance in a model system of an aqueous standard mixture of FFAs at a pH of 3.5 was compared to that of the more commonly used sodium chloride (NaCl) and sodium sulfate (Na2SO4). All of the salts and salt systems evaluated, in proper amount, gave improved results compared to NaCl (saturated), which instead gave interesting results only for the least volatile FFAs C8 and C10. For C2-C6, the salt system that gave the best results compared to NaCl was (NH4)2SO4/NaH2PO4, in the highest of the four amounts evaluated, with factor increases between 1.2 and 4.1-fold, and NaH2PO4, between 1.0 and 4.3-fold. The SPME extraction efficiency given by the mixture (NH4)2SO4/NaH2PO4 was also assessed on biological and food samples, confirming that overall it performed better than NaCl. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. A New Slow Releasing, H2S Generating Compound, GYY4137 Relaxes Spontaneous and Oxytocin-Stimulated Contractions of Human and Rat Pregnant Myometrium

    PubMed Central

    Robinson, Hayley; Wray, Susan

    2012-01-01

    Better tocolytics are required to help prevent preterm labour. The gaseotransmitter Hydrogen sulphide (H2S) has been shown to reduce myometrial contractility and thus is of potential interest. However previous studies used NaHS, which is toxic and releases H2S as a non-physiological bolus and thus alternative H2S donors are sought. GYY4137 has been developed to slowly release H2S and hence better reflect endogenous physiological release. We have examined its effects on spontaneous and oxytocin-stimulated contractility and compared them to NaHS, in human and rat myometrium, throughout gestation. The effects on contractility in response to GYY4137 (1 nM–1 mM) and NaHS (1 mM) were examined on myometrial strips from, biopsies of women undergoing elective caesarean section or hysterectomy, and from non-pregnant, 14, 18, 22 day (term) gestation or labouring rats. In pregnant rat and human myometrium dose-dependent and significant decreases in spontaneous contractions were seen with increasing concentrations of GYY4137, which also reduced underlying Ca transients. GYY4137 and NaHS significantly reduced oxytocin-stimulated and high-K depolarised contractions as well as spontaneous activity. Their inhibitory effects increased as gestation advanced, but were abruptly reversed in labour. Glibenclamide, an inhibitor of ATP-sensitive potassium (KATP) channels, abolished the inhibitory effect of GYY4137. These data suggest (i) H2S contributes to uterine quiescence from mid-gestation until labor, (ii) that H2S affects L-type calcium channels and KATP channels reducing Ca entry and thereby myometrial contractions, (iii) add to the evidence that H2S plays a physiological role in relaxing myometrium, and thus (iv) H2S is an attractive target for therapeutic manipulation of human myometrial contractility. PMID:23029460

  12. Hydrogen Sulfide Alleviates Aluminum Toxicity via Decreasing Apoplast and Symplast Al Contents in Rice.

    PubMed

    Zhu, Chun Q; Zhang, Jun H; Sun, Li M; Zhu, Lian F; Abliz, Buhailiqem; Hu, Wen J; Zhong, Chu; Bai, Zhi G; Sajid, Hussain; Cao, Xiao C; Jin, Qian Y

    2018-01-01

    Hydrogen sulfide (H 2 S) plays a vital role in Al 3+ stress resistance in plants, but the underlying mechanism is unclear. In the present study, pretreatment with 2 μM of the H 2 S donor NaHS significantly alleviated the inhibition of root elongation caused by Al toxicity in rice roots, which was accompanied by a decrease in Al contents in root tips under 50 μM Al 3+ treatment. NaHS pretreatment decreased the negative charge in cell walls by reducing the activity of pectin methylesterase and decreasing the pectin and hemicellulose contents in rice roots. This treatment also masked Al-binding sites in the cell wall by upregulating the expression of OsSATR1 and OsSTAR2 in roots and reduced Al binding in the cell wall by stimulating the expression of the citrate acid exudation gene OsFRDL4 and increasing the secretion of citrate acid. In addition, NaHS pretreatment decreased the symplasmic Al content by downregulating the expression of OsNRAT1 , and increasing the translocation of cytoplasmic Al to the vacuole via upregulating the expression of OsALS1 . The increment of antioxidant enzyme [superoxide dismutase (SOD), ascorbate peroxidase (APX), catalase (CAT), and peroxidase (POD)] activity with NaHS pretreatment significantly decreased the MDA and H 2 O 2 content in rice roots, thereby reducing the damage of Al 3+ toxicity on membrane integrity in rice. H 2 S exhibits crosstalk with nitric oxide (NO) in response to Al toxicity, and through reducing NO content in root tips to alleviate Al toxicity. Together, this study establishes that H 2 S alleviates Al toxicity by decreasing the Al content in the apoplast and symplast of rice roots.

  13. Hydrogen sulfide accelerates the recovery of kidney tubules after renal ischemia/reperfusion injury.

    PubMed

    Han, Sang Jun; Kim, Jee In; Park, Jeen-Woo; Park, Kwon Moo

    2015-09-01

    Progression of acute kidney injury to chronic kidney disease (CKD) is associated with inadequate recovery of damaged kidney. Hydrogen sulfide (H2S) regulates a variety of cellular signals involved in cell death, differentiation and proliferation. This study aimed to identify the role of H2S and its producing enzymes in the recovery of kidney following ischemia/reperfusion (I/R) injury. Mice were subjected to 30 min of bilateral renal ischemia. Some mice were administered daily NaHS, an H2S donor, and propargylglycine (PAG), an inhibitor of the H2S-producing enzyme cystathionine gamma-lyase (CSE), during the recovery phase. Cell proliferation was assessed via 5'-bromo-2'-deoxyuridine (BrdU) incorporation assay. Ischemia resulted in decreases in CSE and cystathionine beta-synthase (CBS) expression and activity, and H2S level in the kidney. These decreases did not return to sham level until 8 days after ischemia when kidney had fibrotic lesions. NaHS administration to I/R-injured mice accelerated the recovery of renal function and tubule morphology, whereas PAG delayed that. Furthermore, PAG increased mortality after ischemia. NaHS administration to I/R-injured mice accelerated tubular cell proliferation, whereas it inhibited interstitial cell proliferation. In addition, NaHS treatment reduced post-I/R superoxide formation, lipid peroxidation, level of GSSG/GSH and Nox4 expression, whereas it increased catalase and MnSOD expression. Our findings demonstrate that H2S accelerates the recovery of I/R-induced kidney damage, suggesting that the H2S-producing transsulfuration pathway plays an important role in kidney repair after acute injury. © The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

  14. Separation, concentration and determination of trace chloramphenicol in shrimp from different waters by using polyoxyethylene lauryl ether-salt aqueous two-phase system coupled with high-performance liquid chromatography.

    PubMed

    Lu, Yang; Yao, Hui; Li, Chuang; Han, Juan; Tan, Zhenjiang; Yan, Yongsheng

    2016-02-01

    Polyoxyethylene lauryl ether (POELE10)-NaH2PO4 aqueous two-phase extraction system (ATPES) is coupled with HPLC to analyze chloramphenicol (CAP) in aquatic product. Response surface methodology (RSM) was adopted in the multi-factor experiment to determine the optimized conditions. The extraction efficiency of CAP (E%) is up to 99.42% under the optimal conditions, namely, the concentration of NaH2PO4, the concentration of POELE10, pH and temperature were 0.186 g · mL(-1), 0.033 g · mL(-1), 3.8 and 25 °C respectively. The optimal value of enrichment factor of CAP (F) was 22.56 when the concentration of NaH2PO4 was 0.192 g · mL(-1), the concentration of POELE10 was 0.024 g/ml, pH was 4.2 and temperature was 30 °C. The limit of detection (LOD) and limit of quantification (LOQ) of this method are 0.8 μg · kg(-1) and 1 μg · kg(-1), which meet the needs of determining trace or ultratrace CAP in food. The E% and F of this technique are much better than other extraction methods. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. H2S protects against methionine-induced oxidative stress in brain endothelial cells.

    PubMed

    Tyagi, Neetu; Moshal, Karni S; Sen, Utpal; Vacek, Thomas P; Kumar, Munish; Hughes, William M; Kundu, Soumi; Tyagi, Suresh C

    2009-01-01

    Homocysteine (Hcy) causes cerebrovascular dysfunction by inducing oxidative stress. However, to date, there are no strategies to prevent Hcy-induced oxidative damage. Hcy is an H2S precursor formed from methionine (Met) metabolism. We aimed to investigate whether H2S ameliorated Met-induced oxidative stress in mouse brain endothelial cells (bEnd3). The bEnd3 cells were exposed to Met treatment in the presence or absence of NaHS (donor of H2S). Met-induced cell toxicity increased the levels of free radicals in a concentration-dependent manner. Met increased NADPH-oxidase-4 (NOX-4) expression and mitigated thioredxion-1(Trx-1) expression. Pretreatment of bEnd3 with NaHS (0.05 mM) attenuated the production of free radicals in the presence of Met and protected the cells from oxidative damage. Furthermore, NaHS enhanced inhibitory effects of apocynin, N-acetyl-l-cysteine (NAC), reduced glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), Nomega-nitro-l-arginine methyl ester (L-NAME) on ROS production and redox enzymes levels induced by Met. In conclusion, the administration of H2S protected the cells from oxidative stress induced by hyperhomocysteinemia (HHcy), which suggested that NaHS/H2S may have therapeutic potential against Met-induced oxidative stress.

  16. Protective Effects of Hydrogen Sulfide in the Ageing Kidney.

    PubMed

    Hou, Cui-Lan; Wang, Ming-Jie; Sun, Chen; Huang, Yong; Jin, Sheng; Mu, Xue-Pan; Chen, Ying; Zhu, Yi-Chun

    2016-01-01

    Aims . The study aimed to examine whether hydrogen sulfide (H 2 S) generation changed in the kidney of the ageing mouse and its relationship with impaired kidney function. Results . H 2 S levels in the plasma, urine, and kidney decreased significantly in ageing mice. The expression of two known H 2 S-producing enzymes in kidney, cystathionine γ -lyase (CSE) and cystathionine- β -synthase (CBS), decreased significantly during ageing. Chronic H 2 S donor (NaHS, 50  μ mol/kg/day, 10 weeks) treatment could alleviate oxidative stress levels and renal tubular interstitial collagen deposition. These protective effects may relate to transcription factor Nrf2 activation and antioxidant proteins such as HO-1, SIRT1, SOD1, and SOD2 expression upregulation in the ageing kidney after NaHS treatment. Furthermore, the expression of H 2 S-producing enzymes changed with exogenous H 2 S administration and contributed to elevated H 2 S levels in the ageing kidney. Conclusions . Endogenous hydrogen sulfide production in the ageing kidney is insufficient. Exogenous H 2 S can partially rescue ageing-related kidney dysfunction by reducing oxidative stress, decreasing collagen deposition, and enhancing Nrf2 nuclear translocation. Recovery of endogenous hydrogen sulfide production may also contribute to the beneficial effects of NaHS treatment.

  17. Hydrogen sulfide protects cardiomyocytes from hypoxia/reoxygenation-induced apoptosis by preventing GSK-3beta-dependent opening of mPTP.

    PubMed

    Yao, Ling-Ling; Huang, Xiao-Wei; Wang, Yong-Gang; Cao, Yin-Xiang; Zhang, Cai-Cai; Zhu, Yi-Chun

    2010-05-01

    Hydrogen sulfide (H(2)S) is an endogenously generated gaseous transmitter, which has recently been suggested to regulate cardiovascular functions. The present study aims to clarify the mechanisms underlying the cardioprotective effects of H(2)S. Signaling elements were examined in cardiomyocytes cultured under hypoxia/reoxygenation conditions and in a rat model of ischemia-reperfusion. In cultured cardiomyocytes, sodium hydrosulfide (NaHS; 10, 30, and 50 mumol/l) showed concentration-dependent inhibitory effects on cardiomyocyte apoptosis induced by hypoxia/reoxygenation. These effects were associated with an increase in phosphorylation of glycogen synthase kinase-3beta (GSK-3beta) (Ser9) and a decrease in Bax translocation, caspase-3 activation, and mitochondrial permeability transition pore (mPTP) opening. Transfection of a phosphorylation-resistant mutant of GSK-3beta at Ser9 attenuated the effects of NaHS in reducing cardiomyocyte apoptosis, Bax translocation, caspase-3 activation, and mPTP opening. In a rat model of ischemia-reperfusion, NaHS administration reduced myocardial infarct size and increased the phosphorylation of GSK-3beta (Ser9) at a dose of 30 mumol/kg. In conclusion, the H(2)S donor prevents cardiomyocyte apoptosis by inducing phosphorylation of GSK-3beta (Ser9) and subsequent inhibition of mPTP opening.

  18. Hip arthroscopy versus open surgical dislocation for femoroacetabular impingement

    PubMed Central

    Zhang, Dagang; Chen, Long; Wang, Guanglin

    2016-01-01

    Abstract Background: This meta-analysis aims to evaluate the efficacy and safety of hip arthroscopy versus open surgical dislocation for treating femoroacetabular impingement (FAI) through published clinical trials. Methods: We conducted a comprehensive literature search using PUBMED, EMBASE, and the Cochrane Central Register of Controlled Trials databases for relevant studies on hip arthroscopy and open surgical dislocation as treatment options for FAI. Results: Compared with open surgical dislocation, hip arthroscopy resulted in significantly higher Nonarthritic Hip Scores (NAHS) at 3- and 12-month follow-ups, a significant improvement in NAHS from preoperation to 3 months postoperation, and a significantly lower reoperation rate. Open surgical dislocation resulted in a significantly improved alpha angle by the Dunn view in patients with cam osteoplasty from preoperation to postoperation, compared with hip arthroscopy. This meta-analysis demonstrated no significant differences in the modified Harris Hip Score, Hip Outcome Score-Activities of Daily Living, or Hip Outcome Score-Sport Specific Subscale at 12 months of follow-up, or in complications (including nerve damage, wound infection, and wound dehiscence). Conclusion: Hip arthroscopy resulted in higher NAHS and lower reoperation rates, but had less improvement in alpha angle in patients with cam osteoplasty, than open surgical dislocation. PMID:27741133

  19. Disinhibition of the ammonium nitrogen in autothermal thermophilic aerobic digestion for sewage sludge by chemical precipitation.

    PubMed

    Yuan, Haiping; Xu, Changwen; Zhu, Nanwen

    2014-10-01

    Magnesium ammonium phosphate (MAP) precipitation was introduced to remove ammonium nitrogen (NH4(+)-N) in autothermal thermophilic aerobic digestion (ATAD) in this study by addition of MgCl2 · 6H2O and NaH2PO4 · 2H2O. The results showed that the lowest NH4(+)-N concentration was found in the D2 digester after 2nd day dosing treatment and 38.12% of VS removal efficiency was obtained after 15 days ATAD treatment. Sludge stabilization was achieved in the D2 digester 6 days earlier than the non-dosing digester when 8.7 g/L MgCl2 · 6H2O and 6.7 g/L NaH2PO4 · 2H2O were added into the digester. Furthermore, the highest VS removal efficiency of 40.03% was observed after 21 days digestion in D2 digesters. Therefore, MAP precipitation was an effective method for the ammonium nitrogen disinhibition when 8.7 g/L MgCl2 · 6H2O and 6.7 g/L NaH2PO4 · 2H2O were added into on the 2nd day after the digester startup. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Optical response of the sodium alanate system: GW0-BSE calculations and thin film measurements

    NASA Astrophysics Data System (ADS)

    van Setten, M. J.; Gremaud, R.; Brocks, G.; Dam, B.; Kresse, G.; de Wijs, G. A.

    2011-01-01

    We calculate from first principles the optical spectra of the hydrides in the sodium alanate hydrogen storage system: NaH, NaAlH4, and Na3AlH6. In particular we study the effects of systematic improvements of the theoretical description. To benchmark the calculations we also measure the optical response of a thin film of NaH. The simplest calculated dielectric functions are based upon independent electrons and holes, whose spectrum is obtained at the G0W0 level. Successive improvements consist of including partial self-consistency (so-called GW0) and account for excitonic effects, using the Bethe-Salpeter equation (BSE). Each improvement gives a sizable blue shift or red shift of the dielectric functions, but conserves the trend in the optical gap among different materials. Whereas these shifts partially cancel at the highest (GW0-BSE) level of approximation, the shape of the dielectric functions is strongly modified by excitonic effects. Calculations at the GW0-BSE level give a good agreement with the dielectric function of NaH extracted from the measurements. It demonstrates that the approach can be used for a quantitative interpretation of spectra in novel hydrogen storage materials obtained via, e.g., hydrogenography.

  1. Molekulare Diagnostik von Hautinfektionen am Paraffinmaterial - Übersicht und interdisziplinärer Konsensus.

    PubMed

    Sunderkötter, Cord; Becker, Karsten; Kutzner, Heinz; Meyer, Thomas; Blödorn-Schlicht, Norbert; Reischl, Udo; Nenoff, Pietro; Geißdörfer, Walter; Gräser, Yvonne; Herrmann, Mathias; Kühn, Joachim; Bogdan, Christian

    2018-02-01

    Nukleinsäure-Amplifikations-Techniken (NAT), wie die PCR, sind hochsensitiv sowie selektiv und stellen in der mikrobiologischen Diagnostik wertvolle Ergänzungen zur kulturellen Anzucht und Serologie dar. Sie bergen aber gerade bei formalinfixiertem und in Paraffin eingebettetem Gewebe ein Risiko für sowohl falsch negative als auch falsch positive Resultate, welches nicht immer richtig eingeschätzt wird. Daher haben Vertreter der Deutschen Gesellschaft für Hygiene und Mikrobiologie (DGHM) und der Deutschen Dermatologischen Gesellschaft (DDG) einen Konsensus in Form einer Übersichtsarbeit erarbeitet, wann eine NAT am Paraffinschnitt angezeigt und sinnvoll ist und welche Punkte dabei in der Präanalytik und Befundinterpretation beachtet werden müssen. Da bei Verdacht auf eine Infektion grundsätzlich Nativgewebe genutzt werden soll, ist die PCR am Paraffinschnitt ein Sonderfall, wenn beispielsweise bei erst nachträglichaufgekommenem Verdacht auf eine Infektion kein Nativmaterial zur Verfügung steht und nicht mehr gewonnen werden kann. Mögliche Indikationen sind der histologisch erhobene Verdacht auf eine Leishmaniose, eine Infektion durch Bartonellen oder Rickettsien, oder ein Ecthyma contagiosum. Nicht sinnvoll ist oder kritisch gesehen wird eine NAT am Paraffinschnitt zum Beispiel bei Infektionen mit Mykobakterien oder RNA-Viren. Die Konstellation für eine NAT aus Paraffingewebe sollte jeweils benannt werden, die erforderliche Prä-Analytik, die jeweiligen Grenzen des Verfahrens und die diagnostischen Alternativen bekannt sein. Der PCR-Befund sollte entsprechend kommentiert werden, um Fehleinschätzungen zu vermeiden. © 2018 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

  2. Koedukation oder Geschlechtertrennung = Coeducation or Gender Segregation.

    ERIC Educational Resources Information Center

    Baumert, Jurgen

    1992-01-01

    Presents study results examining recruitment practice differences between coeducational and gender segregated secondary schools in Germany. Discusses the impact of organizational form on teacher judgments, achievement in specific subjects, school subject-related interests, and school commitment. Reports that under conditions of free school choice,…

  3. Einleitung

    NASA Astrophysics Data System (ADS)

    Ha, Suk-Woo

    Der Einsatz von Implantaten zielt auf die Unterstützung oder den Ersatz von Zelloder Gewebefunktionen im menschlichen Körper. Die Werkstoffauswahl für diese Implantate hängt dabei von der Art und der Funktion des zu ersetzenden Gewebes ab. Die Anforderungen an den Implantatwerkstoff bezüglich Eigenschaften und Struktur können je nach Implantationsort und Funktionalität ganz unterschiedlich sein. Implantate, die im Knochengewebe Funktionen der Lasteinleitung und -überleitung ausüben, sind hohen mechanischen Anforderungen (optimale Bauteilsteifigkeit, Dauerfestigkeit) unterworfen, während bei Blutgefässimplantaten die Werkstoffoberfläche, primär in ihrer chemischen Zusammensetzung derart gestaltet sein muss, dass eine minimale Thrombogenität resultiert. Für den Erfolg des Implantatwerkstoffes oder -bauteils sind folgende drei Faktoren relevant: (a) Biokompatibilität, (b) Gesundheitszustand des Patienten und (c) Verlauf der Operation und der nachfolgenden Therapie. Bei Vorliegen einer Erkrankung, wie z. B. die allergische Sensibilisierung gegenüber Metallionen (Nickelallergie) oder Osteoporose im Fall der Verankerung von Hüftprothesen, ist der Implantatwerkstoff höheren Anforderungen bezüglich der Biokompatibilität unterworfen als bei organisch gesunden Patienten.

  4. Enhanced Salt Tolerance Conferred by the Complete 2.3 kb cDNA of the Rice Vacuolar Na+/H+ Antiporter Gene Compared to 1.9 kb Coding Region with 5′ UTR in Transgenic Lines of Rice

    PubMed Central

    Amin, U. S. M.; Biswas, Sudip; Elias, Sabrina M.; Razzaque, Samsad; Haque, Taslima; Malo, Richard; Seraj, Zeba I.

    2016-01-01

    Soil salinity is one of the most challenging problems that restricts the normal growth and production of rice worldwide. It has therefore become very important to produce more saline tolerant rice varieties. This study shows constitutive over-expression of the vacuolar Na+/H+ antiporter gene (OsNHX1) from the rice landrace (Pokkali) and attainment of enhanced level of salinity tolerance in transgenic rice plants. It also shows that inclusion of the complete un-translated regions (UTRs) of the alternatively spliced OsNHX1 gene provides a higher level of tolerance to the transgenic rice. Two separate transformation events of the OsNHX1 gene, one with 1.9 kb region containing the 5′ UTR with CDS and the other of 2.3 kb, including 5′ UTR, CDS, and the 3′ UTR regions were performed. The transgenic plants with these two different constructs were advanced to the T3 generation and physiological and molecular screening of homozygous plants was conducted at seedling and reproductive stages under salinity (NaCl) stress. Both transgenic lines were observed to be tolerant compared to WT plants at both physiological stages. However, the transgenic lines containing the CDS with both the 5′ and 3′ UTR were significantly more tolerant compared to the transgenic lines containing OsNHX1 gene without the 3′ UTR. At the seedling stage at 12 dS/m stress, the chlorophyll content was significantly higher (P < 0.05) and the electrolyte leakage significantly lower (P < 0.05) in the order 2.3 kb > 1.9 kb > and WT lines. Yield in g/plant in the best line from the 2.3 kb plants was significantly more (P < 0.01) compared, respectively, to the best 1.9 kb line and WT plants at stress of 6 dS/m. Transformation with the complete transcripts rather than the CDS may therefore provide more durable level of tolerance. PMID:26834778

  5. Acidic pH and short-chain fatty acids activate Na+ transport but differentially modulate expression of Na+/H+ exchanger isoforms 1, 2, and 3 in omasal epithelium.

    PubMed

    Lu, Zhongyan; Yao, Lei; Jiang, Zhengqian; Aschenbach, Jörg R; Martens, Holger; Shen, Zanming

    2016-01-01

    Low sodium content in feed and large amounts of salivary sodium secretion are essential requirements to efficient sodium reabsorption in the dairy cow. It is already known that Na(+)/H(+) exchange (NHE) of the ruminal epithelium plays a key role in Na(+) absorption, and its function is influenced by the presence of short-chain fatty acids (SCFA) and mucosal pH. By contrast, the functional role and regulation of NHE in omasal epithelium have not been completely understood. In the present study, we used model studies in small ruminants (sheep and goats) to investigate NHE-mediated Na(+) transport and the effects of pH and SCFA on NHE activity in omasal epithelium and on the expression of NHE isoform in omasal epithelial cells. Conventional Ussing chamber technique, primary cell culture, quantitative PCR, and Western blot were used. In native omasal epithelium of sheep, the Na(+) transport was electroneutral, and it was inhibited by the specific NHE3 inhibitor 3-[2-(3-guanidino-2-methyl-3-oxo-propenyl)-5-methyl-phenyl]-N-isopropylidene-2-methyl-acrylamide dihydrochloride, which decreased mucosal-to-serosal, serosal-to-mucosal, and net flux rates of Na(+) by 80% each. The application of low mucosal pH (6.4 or 5.8) in the presence of SCFA activated the Na(+) transport across omasal epithelium of sheep compared with that at pH 7.4. In cultured omasal epithelial cells of goats, mRNA and protein of NHE1, NHE2, and NHE3 were detected. The application of SCFA increased NHE1 mRNA and protein expression, which was most prominent when the culture medium pH decreased from 7.4 to 6.8. At variance, the mRNA and protein expression of NHE2 and NHE3 were decreased with low pH and SCFA, which was contrary to the published data from ruminal epithelial studies. In conclusion, this paper shows that (1) NHE1, NHE2, and NHE3 are expressed in omasal epithelium; (2) NHE3 mediates the major portion of transepithelial Na(+) transport in omasal epithelium; and (3) SCFA and acidic pH acutely

  6. Exogenous application of hydrogen sulfide donor sodium hydrosulfide enhanced multiple abiotic stress tolerance in bermudagrass (Cynodon dactylon (L). Pers.).

    PubMed

    Shi, Haitao; Ye, Tiantian; Chan, Zhulong

    2013-10-01

    As a gaseous molecule, hydrogen sulfide (H2S) has been recently found to be involved in plant responses to multiple abiotic stress. In this study, salt (150 and 300 mM NaCl), osmotic (15% and 30% PEG6000) and cold (4 °C) stress treatments induced accumulation of endogenous H2S level, indicating that H2S might play a role in bermudagrass responses to salt, osmotic and cold stresses. Exogenous application of H2S donor (sodium hydrosulfide, NaHS) conferred improved salt, osmotic and freezing stress tolerances in bermudagrass, which were evidenced by decreased electrolyte leakage and increased survival rate under stress conditions. Additionally, NaHS treatment alleviated the reactive oxygen species (ROS) burst and cell damage induced by abiotic stress, via modulating metabolisms of several antioxidant enzymes [catalase (CAT), peroxidase (POD) and GR (glutathione reductase)] and non-enzymatic glutathione antioxidant pool and redox state. Moreover, exogenous NaHS treatment led to accumulation of osmolytes (proline, sucrose and soluble total sugars) in stressed bermudagrass plants. Taken together, all these data indicated the protective roles of H2S in bermudagrass responses to salt, osmotic and freezing stresses, via activation of the antioxidant response and osmolyte accumulation. These findings might be applicable to grass and crop engineering to improve abiotic stress tolerance. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  7. H2S Protects Against Methionine–Induced Oxidative Stress in Brain Endothelial Cells

    PubMed Central

    Tyagi, Neetu; Moshal, Karni S.; Sen, Utpal; Vacek, Thomas P.; Kumar, Munish; Hughes, William M.; Kundu, Soumi

    2009-01-01

    Abstract Homocysteine (Hcy) causes cerebrovascular dysfunction by inducing oxidative stress. However, to date, there are no strategies to prevent Hcy-induced oxidative damage. Hcy is an H2S precursor formed from methionine (Met) metabolism. We aimed to investigate whether H2S ameliorated Met-induced oxidative stress in mouse brain endothelial cells (bEnd3). The bEnd3 cells were exposed to Met treatment in the presence or absence of NaHS (donor of H2S). Met-induced cell toxicity increased the levels of free radicals in a concentration-dependent manner. Met increased NADPH-oxidase-4 (NOX-4) expression and mitigated thioredxion-1(Trx-1) expression. Pretreatment of bEnd3 with NaHS (0.05 mM) attenuated the production of free radicals in the presence of Met and protected the cells from oxidative damage. Furthermore, NaHS enhanced inhibitory effects of apocynin, N-acetyl-l-cysteine (NAC), reduced glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), Nω-nitro-l-arginine methyl ester (L-NAME) on ROS production and redox enzymes levels induced by Met. In conclusion, the administration of H2S protected the cells from oxidative stress induced by hyperhomocysteinemia (HHcy), which suggested that NaHS/H2S may have therapeutic potential against Met-induced oxidative stress. Antioxid. Redox Signal. 11, 25–33. PMID:18837652

  8. Protective role of hydrogen sulfide against noise-induced cochlear damage: a chronic intracochlear infusion model.

    PubMed

    Li, Xu; Mao, Xiao-Bo; Hei, Ren-Yi; Zhang, Zhi-Bin; Wen, Li-Ting; Zhang, Peng-Zhi; Qiu, Jian-Hua; Qiao, Li

    2011-01-01

    A reduction in cochlear blood flow plays an essential role in noise-induced hearing loss (NIHL). The timely regulation of cochlear perfusion determines the progression and prognosis of NIHL. Hydrogen sulfide (H(2)S) has attracted increasing interest as a vasodilator in cardiovascular systems. This study identified the role of H(2)S in cochlear blood flow regulation and noise protection. The gene and protein expression of the H(2)S synthetase cystathionine-γ-lyase (CSE) in the rat cochlea was examined using immunofluorescence and real-time PCR. Cochlear CSE mRNA levels varied according to the duration of noise exposure. A chronic intracochlear infusion model was built and artificial perilymph (AP), NaHS or DL-propargylglycine (PPG) were locally administered. Local sodium hydrosulfide (NaHS) significantly increased cochlear perfusion post-noise exposure. Cochlear morphological damage and hearing loss were alleviated in the NaHS group as measured by conventional auditory brainstem response (ABR), cochlear scanning electron microscope (SEM) and outer hair cell (OHC) count. The highest percentage of OHC loss occurred in the PPG group. Our results suggest that H(2)S plays an important role in the regulation of cochlear blood flow and the protection against noise. Further studies may identify a new preventive and therapeutic perspective on NIHL and other blood supply-related inner ear diseases.

  9. Salicylic acid is required for Mi-1-mediated resistance of tomato to whitefly Bemisia tabaci, but not for basal defense to this insect pest.

    PubMed

    Rodríguez-Álvarez, C I; López-Climent, M F; Gómez-Cadenas, A; Kaloshian, I; Nombela, G

    2015-10-01

    Plant defense to pests or pathogens involves global changes in gene expression mediated by multiple signaling pathways. A role for the salicylic acid (SA) signaling pathway in Mi-1-mediated resistance of tomato (Solanum lycopersicum) to aphids was previously identified and its implication in the resistance to root-knot nematodes is controversial, but the importance of SA in basal and Mi-1-mediated resistance of tomato to whitefly Bemisia tabaci had not been determined. SA levels were measured before and after B. tabaci infestation in susceptible and resistant Mi-1-containing tomatoes, and in plants with the NahG bacterial transgene. Tomato plants of the same genotypes were also screened with B. tabaci (MEAM1 and MED species, before known as B and Q biotypes, respectively). The SA content in all tomato genotypes transiently increased after infestation with B. tabaci albeit at variable levels. Whitefly fecundity or infestation rates on susceptible Moneymaker were not significantly affected by the expression of NahG gene, but the Mi-1-mediated resistance to B. tabaci was lost in VFN NahG plants. Results indicated that whiteflies induce both SA and jasmonic acid accumulation in tomato. However, SA has no role in basal defense of tomato against B. tabaci. In contrast, SA is an important component of the Mi-1-mediated resistance to B. tabaci in tomato.

  10. Chronic aerobic exercise training alleviates myocardial fibrosis in aged rats through restoring bioavailability of hydrogen sulfide.

    PubMed

    Ma, Ning; Liu, Hong-Mei; Xia, Ting; Liu, Jian-Dong; Wang, Xiao-Ze

    2018-06-02

    Age-related fibrosis is attenuated by aerobic exercise; however, little is known concerning the underlying molecular mechanism. To address this question, aged rats were given moderate-intensity exercise for 12 weeks. After exercise in aged rats, hydrogen sulfide (H2S) levels in plasma and heart increased 39.8% and 90.9%, respectively. Exercise upregulated expression of cystathionine γ-lyase (CSE) and 3-mercaptopyruvate sulfurtransferase (3-MST) in heart of aged rats. Furthermore, aged rats were given moderate-intensity exercise for 12 weeks or treated with NaHS (intraperitoneal injection of 0.1 ml/kg/day of 0.28 mol/l NaHS). After exercise in aged rats, Masson-trichrome staining area decreased 34.8% and myocardial hydroxyproline levels decreased 29.6%. Exercise downregulated expression of collagen-I and α-SMA in heart of aged rats. Exercise in aged rats reduced malondialdehyde levels in plasma and heart and 3-nitrotyrosine in heart. Exercise in aged rats reduced mRNA and protein expression of CHOP, GRP78, and XBP1. Exercise also reduced mRNA and protein expression of IL-6 and MCP-1 and suppressed activation of JNK in aging heart. Similar effects were demonstrated in aged rats treated with NaHS. Collectively, exercise restored bioavailability of hydrogen sulfide in the heart of aged rats, which partly explained the benefits of exercise against myocardial fibrosis of aged population.

  11. Organisationsaspekte in der Umsetzung

    NASA Astrophysics Data System (ADS)

    Balck, Henning; Bungard, Walter; Hofmann, Karsten; Ganz, Walter; Schwenker, Burkhard; Hanßen, Dirk; Meindl, Rudolf; Schloske, Alexander; Thieme, Paul; Teufel, Peter

    Strukturbrüche sind eine der Hauptursachen für die Schwierigkeiten vieler Unternehmen, ihre Organisationsform zu modernisieren und vor allem turbulenten Marktbedingungen anzupassen. Klassische Beispiele für Strukturbrüche finden sich in der Spaltung von Aufbau- und Ablauforganisation, der Spaltung von Produktion und Dienstleistung oder der Spaltung von Planung und Ausführung. Ein wirkungsvoller Ansatz zur Überwindung solcher Spaltungen ist eine Art Versöhnungsmuster: die Polare Organisation. Wesentliche Elemente dieser Organisationsform sind ihr Netzwerkcharakter, kooperatives Zusammenwirken, eine hohe Kommunikationsintensität und eine polare Koppelung der kommunizierenden Partner oder - in abstrahierter Form - die organisierte Balance erfolgskritischer Gegensätze, wie Kosten und Qualität.

  12. Hydrogen sulfide (H2S) attenuates uranium-induced acute nephrotoxicity through oxidative stress and inflammatory response via Nrf2-NF-κB pathways.

    PubMed

    Zheng, Jifang; Zhao, Tingting; Yuan, Yan; Hu, Nan; Tang, Xiaoqing

    2015-12-05

    As an endogenous gaseous mediator, H2S exerts anti-oxidative, anti-inflammatory and cytoprotective effects in kidneys. This study was designed to investigate the protective effect of H2S against uranium-induced nephrotoxicity in adult SD male rats after in vivo effect of uranium on endogenous H2S formation was explored in kidneys. The levels of endogenous H2S and H2S-producing enzymes (CBS and CSE) were measured in renal homogenates from rats intoxicated by an intraperitoneally (i.p.) injection of uranyl acetate at a single dose of 2.5, 5 or 10 mg/kg. In rats injected i.p. with uranyl acetate (5 mg/kg) or NaHS (an H2S donor, 28 or 56 μmol/kg) alone or in combination, we determined biochemical parameters and histopathological alteration to assess kidney function, examined oxidative stress markers, and investigated Nrf2 and NF-κB pathways in kidney homogenates. The results suggest that uranium intoxication in rats decreased endogenous H2S generation as well as CBS and CSE protein expression. NaHS administration in uranium-intoxicated rats ameliorated the renal biochemical indices and histopathological effects, lowered MDA accumulation, and restored GSH level and anti-oxidative enzymes activities like SOD, CAT, GPx and GST. NaHS treatment in uranium-intoxicated rats activated uranium-inhibited protein expression and nuclear translocation of transcription factor Nrf2, which increased protein expression of downstream target-Nrf2 genes HO-1, NQO-1, GCLC, and TXNRD-1. NaHS administration in uranium-intoxicated rats inhibited uranium-induced nuclear translocation and phosphorylation of transcription factor κB/p65, which decreased protein expression of target-p65 inflammatory genes TNF-α, iNOS, and COX-2. Taken together, these data implicate that H2S can afford protection to rat kidneys against uranium-induced adverse effects through induction of antioxidant defense by activating Nrf2 pathway and reduction of inflammatory response by suppressing NF-κB pathway

  13. Extreme floods in central Europe over the past 500 years: Role of cyclone pathway ``Zugstrasse Vb''

    NASA Astrophysics Data System (ADS)

    Mudelsee, M.; BöRngen, M.; Tetzlaff, G.; Grünewald, U.

    2004-12-01

    Anthropogenically induced climate change has been hypothesized to add to the risk of extreme river floods because a warmer atmosphere can carry more water. In the case of the central European rivers Elbe and Oder, another possibility that has been considered is a more frequent occurrence of a weather situation of the type "Zugstrasse Vb," where a low-pressure system travels from the Adriatic region northeastward, carrying moist air and bringing orographic rainfall in the mountainous catchment areas (Erzgebirge, Sudeten, and Beskids). Analysis of long, homogeneous records of past floods allows us to test such ideas. M. Mudelsee and co-workers recently presented flood records for the middle parts of the Elbe and Oder, which go continuously back to A.D. 1021 and A.D. 1269, respectively. Here we review the reconstruction and assess the data quality of the records, which are based on combining documentary data from the interval up to 1850 and measurements thereafter, finding both the Elbe and Oder records to provide reliable information on heavy floods at least since A.D. 1500. We explain that the statistical method of kernel occurrence rate estimation can overcome deficiencies of techniques previously used to investigate trends in the occurrence of climatic extremes, because it (1) allows nonmonotonic trends, (2) imposes no parametric restrictions, and (3) provides confidence bands, which are essential for evaluating whether observed trends are real or came by chance into the data. We further give a hypothesis test that can be used to evaluate monotonic trends. On the basis of these data and methods, we find for both the Elbe and Oder rivers (1) significant downward trends in winter flood risk during the twentieth century, (2) no significant trends in summer flood risk in the twentieth century, and (3) significant variations in flood risk during past centuries, with notable differences between the Elbe and Oder. The observed trends are shown to be both robust against

  14. Enhanced uridine 5'-monophosphate production by whole cell of Saccharomyces cerevisiae through rational redistribution of metabolic flux.

    PubMed

    Liu, Dong; Chen, Yong; Li, An; Xie, Jingjing; Xiong, Jian; Bai, Jianxin; Chen, Xiaochun; Niu, Huanqing; Zhou, Tao; Ying, Hanjie

    2012-06-01

    A whole-cell biocatalytic process for uridine 5'-monophosphate (UMP) production from orotic acid by Saccharomyces cerevisiae was developed. To rationally redistribute the metabolic flux between glycolysis and pentose phosphate pathway, statistical methods were employed first to find out the critical factors in the process. NaH(2)PO(4), MgCl(2) and pH were found to be the important factors affecting UMP production significantly. The levels of these three factors required for the maximum production of UMP were determined: NaH(2)PO(4) 22.1 g/L; MgCl(2) 2.55 g/L; pH 8.15. An enhancement of UMP production from 6.12 to 8.13 g/L was achieved. A significant redistribution of metabolic fluxes was observed and the underlying mechanism was discussed.

  15. Redetermination of the borax structure from laboratory X-ray data at 145 K

    PubMed Central

    Gainsford, Graeme J.; Kemmitt, Tim; Higham, Caleb

    2008-01-01

    The title compound, sodium tetraborate decahydrate (mineral name: borax), Na2[B4O5(OH)4]·8H2O, has been studied previously using X-ray [Morimoto (1956). Miner. J. 2, 1–18] and neutron [Levy & Lisensky (1978). Acta Cryst. B34, 3502–3510] diffraction data. The structure contains tetra­borate anions [B4O5(OH)4]2− with twofold rotation symmetry, which form hydrogen-bonded chains, and [Na(H2O)6] octa­hedra that form zigzag chains [Na(H2O)4/2(H2O)2/1]. The O—H bond distances obtained from the present redetermination at 145 K are shorter than those in the neutron study by an average of 0.127 (19) Å. PMID:21202161

  16. Salicylate effects on proton gradient dissipation by isolated gastric mucosal surface cells.

    PubMed

    Olender, E J; Woods, D; Kozol, R; Fromm, D

    1986-11-01

    The effects of salicylate were examined on Na+/H+ exchange by isolated gastric mucosal surface cells loaded with H+ and resuspended in a buffered medium. Choline salicylate (pH 7.4) increases the dissipation of an intracellular proton gradient which was measured using acridine orange. The exchange of extracellular Na+ with intracellular H+ by surface cells not only remains intact but also is enhanced upon exposure to salicylate. This was confirmed by cellular uptake of 22Na and titration of cellular H+ efflux. Salicylate increases Na+/H+ exchange via a pathway predominantly sensitive to amiloride. However, the data also suggest that salicylate dissipates an intracellular proton gradient by an additional mechanism. The latter is independent of extracellular Na+ and not due to a generalized increase in cellular permeability.

  17. A general radiation model for sound fields and nearfield acoustical holography in wedge propagation spaces.

    PubMed

    Hoffmann, Falk-Martin; Fazi, Filippo Maria; Williams, Earl G; Fontana, Simone

    2017-09-01

    In this work an expression for the solution of the Helmholtz equation for wedge spaces is derived. Such propagation spaces represent scenarios for many acoustical problems where a free field assumption is not eligible. The proposed sound field model is derived from the general solution of the wave equation in cylindrical coordinates, using sets of orthonormal basis functions. The latter are modified to satisfy several boundary conditions representing the reflective behaviour of wedge-shaped propagation spaces. This formulation is then used in the context of nearfield acoustical holography (NAH) and to obtain the expression of the Neumann Green function. The model and its suitability for NAH is demonstrated through both numerical simulations and measured data, where the latter was acquired for the specific case of a loudspeaker on a hemi-cylindrical rigid baffle.

  18. Syntheses, crystal structures, and magnetic properties of the oxalato-bridged mixed-valence complexes (FeII(bpm)3]2[FeIII2(ox)5].8H2O and FeII(bpm)3Na(H2O)2Fe(ox)(3).4H2O (bpm = 2,2'-bipyrimidine).

    PubMed

    Armentano, D; De Munno, G; Faus, J; Lloret, F; Julve, M

    2001-02-12

    The preparation and crystal structures of two oxalato-bridged FeII-FeIII mixed-valence compounds, [FeII(bpm)3]2[FeIII2(ox)5].8H2O (1) and FeII(bpm)3Na(H2O)2FeIII(ox)(3).4H2O (2) (bpm = 2,2'-bipyrimidine; ox = oxalate dianion) are reported here. Complex 1 crystallizes in the triclinic system, space group P1, with a = 10.998(2) A, b = 13.073(3) A, c = 13.308(3) A, alpha = 101.95(2) degrees, beta = 109.20(2) degrees, gamma = 99.89(2) degrees, and Z = 1. Complex 2 crystallizes in the monoclinic system, space group P2(1)/c, with a = 12.609(2) A, b = 19.670(5) A, c = 15.843(3) A, beta = 99.46(1) degrees, and Z = 4. The structure of complex 1 consists of centrosymmetric oxalato-bridged dinuclear high-spin iron(III) [Fe2(ox)5]2- anions, tris-chelated low-spin iron(II) [Fe(bpm)3]2+ cations, and lattice water molecules. The iron atoms are hexacoordinated: six oxygen atoms (iron(III)) from two bidentate and one bisbidentate oxalato ligands and six nitrogen atoms (iron(II)) from three bidentate bpm groups. The Fe(III)-O(ox) and Fe(II)-N(bpm) bond distances vary in the ranges 1.967(3)-2.099(3) and 1.967(4)-1.995(3) A, respectively. The iron(III)-iron(III) separation across the bridging oxalato is 5.449(2) A, whereas the shortest intermolecular iron(III)-iron(II) distance is 6.841(2) A. The structure of complex 2 consists of neutral heterotrinuclear Fe(bpm)2Na(H2O)2Fe(ox)3 units and water molecules of crystallization. The tris-chelated low-spin iron(II) ([Fe(bpm)3]2+) and high-spin iron(III) ([Fe(ox)3]3-) entities act as bidentate ligands (through two bpm-nitrogen and two oxalato-oxygen atoms, respectively) toward the univalent sodium cation, yielding the trinuclear (bpm)2Fe(II)-bpm-Na(I)-ox-Fe(III)(ox)2 complex. Two cis-coordinated water molecules complete the distorted octahedral surrounding of the sodium atom. The ranges of the Fe(II)-N(bpm) and Fe(III)-O(ox) bond distances [1.968(6)-1.993(5) and 1.992(6)-2.024(6) A, respectively] compare well with those observed in 1. The Na

  19. Luftqualität

    NASA Astrophysics Data System (ADS)

    Schultz, Martin G.; Klemp, Dieter; Wahner, Andreas

    Die Qualität der Luft beeinflusst in besonderer Weise die menschliche Gesundheit und hat auch Auswirkungen auf die Landwirtschaft und Ökosysteme. Viele Luftschadstoffe absorbieren oder streuen zudem die Sonnen- oder Wärmestrahlung und sind daher klimawirksam. Luftchemische Prozesse hängen, ebenso wie die Emissionen, von klimatischen Faktoren wie Sonneneinstrahlung, Temperatur und Niederschlag ab. Deshalb ist zu erwarten, dass die projizierten Klimaänderungen für Deutschland auch die Luftschadstoffkonzentrationen beeinflussen werden, auch wenn dieser Zusammenhang noch nicht gut erforscht ist. Dieses Kapitel vermittelt einen Überblick über die Zusammenhänge und weist zumindest qualitativ auf mögliche künftige Entwicklungen hin. Im Vordergrund stehen die Entwicklungen bei Feinstaub und Ozon.

  20. Einleitung

    NASA Astrophysics Data System (ADS)

    Ha, Suk-Woo; Wintermantel, Erich

    Der Aufbau des menschlichen Körpers ist derart komplex, dass die vollständige funktionelle Substitution seiner Strukturen mit künstlichen Werkstoffen und Bauteilen unwahrscheinlich ist. Die meisten heute klinisch eingesetzten Implantate ersetzen in der Regel einfache mechanische oder andere physikalische Funktionen des menschlichen Körpers, die aufgrund eines singulären Defektes im Gewebe oder als Ergebnis einer chronischen Erkrankung substituiert werden müssen. Gelenkprothesen beispielsweise übertragen Lasten, eine künstliche intraokulare Linse ermöglicht Lichttransmission und eine künstliche Arterie sorgt für die Aufrechterhaltung der Blutversorgung. Neben der Funktionserfüllung müssen die medizinisch eingesetzten Werkstoffe zusätzlich den Anforderungen der Körperverträglichkeit genügen, die die vollständige und dauerhafte Aufnahme des Implantates im Körper zum Ziel hat. Die Erkenntnisse der Werkstoffwissenschaft und deren Umsetzung in neue Produkte hat die Entwicklung und Fortschritte in der Medizin und in der Chirurgie entscheidend geprägt. Werkstoffe stehen in ihrem klinischen Einsatz als Temporärimplantate (z. B. Kathetersysteme) sowie als Langzeitimplantate (z. B. Hüftgelenksimplantate oder Herzschrittmacher) in direktem Kontakt mit den Geweben des Körpers und müssen deshalb biokompatibel sein.

  1. Wissenschaft, die unsere Kultur verändert. Tiefenschichten des Streits um die Evolutionstheorie

    NASA Astrophysics Data System (ADS)

    Patzelt, Werner J.

    Die Evolutionstheorie ist eine der erfolgreichsten wissenschaftlichen Theorien. Sie erlaubt es, unsere Herkunft zu verstehen und riskante Merkmale gerade der menschlichen Spezies zu begreifen. Zugleich ist die Evolutionstheorie eine der umstrittensten Theorien. Das liegt nicht an ihrer empirischen Tragfähigkeit, sondern an ihrem Gegenstand. Sie handelt nämlich nicht nur - wie Hunderte andere wissenschaftliche Theorien - von der "Welt da draußen“, sondern vor allem auch von uns selbst und von unserem Platz in dieser Welt. Den einen gilt sie obendrein als Überwinderin religiösen Aberglaubens, den anderen als neuer Zugang zu Gott und seinem Wirken in der Welt. Ferner sehen die einen in der Evolution eine unbezweifelbare Tatsache gleich der Schwerkraft oder dem Holocaust, die anderen aber eine - noch oder dauerhaft - unbewiesene Hypothese oder gar eine falsche Schöpfungslehre. Und während die meisten Streitfragen solcher Art nach wechselseitig akzeptierten Regeln ‚normaler Wissenschaft‘ geklärt werden, wird bei der Frage nach dem Woher unserer Spezies und Kultur die intellektuelle Zuständigkeit von Wissenschaft mitunter überhaupt bezweifelt. Anscheinend geht es schon um recht tiefe Schichten unserer Kultur und nicht nur der wissenschaftlichen, wenn - wie seit 150 Jahren - um die Evolutionstheorie gestritten wird. Wie sehen diese Schichten aus?

  2. Nitric oxide-activated hydrogen sulfide is essential for cadmium stress response in bermudagrass (Cynodon dactylon (L). Pers.).

    PubMed

    Shi, Haitao; Ye, Tiantian; Chan, Zhulong

    2014-01-01

    Nitric oxide (NO) and hydrogen sulfide (H2S) are important gaseous molecules, serving as important secondary messengers in plant response to various biotic and abiotic stresses. However, the interaction between NO and H2S in plant stress response was largely unclear. In this study, endogenous NO and H2S were evidently induced by cadmium stress treatment in bermudagrass, and exogenous applications of NO donor (sodium nitroprusside, SNP) or H2S donor (sodium hydrosulfide, NaHS) conferred improved cadmium stress tolerance. Additionally, SNP and NaHS treatments alleviated cadmium stress-triggered plant growth inhibition, cell damage and reactive oxygen species (ROS) burst, partly via modulating enzymatic and non-enzymatic antioxidants. Moreover, SNP and NaHS treatments also induced the productions of both NO and H2S in the presence of Cd. Interestingly, combined treatments with inhibitors and scavengers of NO and H2S under cadmium stress condition showed that NO signal could be blocked by both NO and H2S inhibitors and scavengers, while H2S signal was specifically blocked by H2S inhibitors and scavengers, indicating that NO-activated H2S was essential for cadmium stress response. Taken together, we assigned the protective roles of endogenous and exogenous NO and H2S in bermudagrass response to cadmium stress, and speculated that NO-activated H2S might be essential for cadmium stress response in bermudagrass. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  3. Hydrogen sulfide facilities production of nitric oxide via the Akt/endothelial nitric oxide synthases signaling pathway to protect human umbilical vein endothelial cells from injury by angiotensin II.

    PubMed

    Cui, Jiasen; Zhuang, Shunjiu; Qi, Shaohong; Li, Li; Zhou, Junwen; Zhang, Wan; Zhao, Yun; Qi, Ning; Yin, Yangjun; Huang, Lu

    2017-11-01

    Angiotensin II (Ang II) has been reported as key in inducing endothelial cell injury, and endothelial cells may produce nitric oxide (NO) to protect themselves. However, the underlying mechanism remains elusive. Human umbilical vein endothelial cells (HUVECs) were divided into five treatment groups as follows: Normal control, Ang II, Ang II + sodium hydrosulfide [NaHS; hydrogen sulfide (H2S) donor], Ang II + Akt inhibitors + NaHS, and Ang II + endothelial nitric oxide synthases (eNOS) inhibitors + NaHS. Subsequently, cell viability, apoptosis, migration, proliferation and adhesion ability were determined. In addition, tubular structure formation was observed, and the NO and phosphorylation levels of Akt and eNOS were evaluated. Compared with the normal control group, Ang II treatment reduced the viability of HUVECs and increased the level of cell apoptosis (P<0.05). Furthermore, Ang II treatment inhibited the phosphorylation level of eNOS and Akt, as well as the generation of NO (P<0.05). H2S reversed the above‑mentioned effects significantly and increased cell proliferation, adhesion ability and promoted tubular structure formation (P<0.05); however, H2S did not reverse the impact of eNOS and Akt phosphorylation levels after being processed with Akt and eNOS inhibitors, which indicates that H2S is capable of protecting HUVECs via the eNOS/Akt signaling pathway (P<0.05). Thus, H2S stimulates the production of NO and protects HUVECs via inducing the Akt/eNOS signaling pathway.

  4. Proanthocyanidin-containing polyphenol extracts from fruits prevent the inhibitory effect of hydrogen sulfide on human colonocyte oxygen consumption.

    PubMed

    Andriamihaja, Mireille; Lan, Annaïg; Beaumont, Martin; Grauso, Marta; Gotteland, Martin; Pastene, Edgar; Cires, Maria Jose; Carrasco-Pozo, Catalina; Tomé, Daniel; Blachier, François

    2018-06-01

    Hydrogen sulfide (H 2 S), a metabolic end product synthesized by the microbiota from L-cysteine, has been shown to act at low micromolar concentration as a mineral oxidative substrate in colonocytes while acting as an inhibitor of oxygen consumption at higher luminal concentrations (65 µM and above). From the previous works showing that polyphenols can bind volatile sulfur compounds, we hypothesized that different dietary proanthocyanidin-containing polyphenol (PACs) plant extracts might modulate the inhibitory effect of H 2 S on colonocyte respiration. Using the model of human HT-29 Glc-/+ cell colonocytes, we show here that pre-incubation of 65 µM of the H 2 S donor NaHS with the different polyphenol extracts markedly reduced the inhibitory effect of NaHS on colonocyte oxygen consumption. Our studies on HT-29 Glc-/+ cell respiration performed in the absence or the presence of PACs reveal rapid binding of H 2 S with the sulfide-oxidizing unit and slower binding of H 2 S to the cytochrome c oxidase (complex IV of the respiratory chain). Despite acute inhibition of colonocyte respiration, no measurable effect of NaHS on paracellular permeability was recorded after 24 h treatment using the Caco-2 colonocyte monolayer model. The results are discussed in the context of the binding of excessive bacterial metabolites by unabsorbed dietary compounds and of the capacity of colonocytes to adapt to changing luminal environment.

  5. Hydrogen sulfide improves diabetic wound healing in ob/ob mice via attenuating inflammation.

    PubMed

    Zhao, Huichen; Lu, Shengxia; Chai, Jiachao; Zhang, Yuchao; Ma, Xiaoli; Chen, Jicui; Guan, Qingbo; Wan, Meiyan; Liu, Yuantao

    2017-09-01

    The proposed mechanisms of impaired wound healing in diabetes involve sustained inflammation, excess oxidative stress and compromised agiogenesis. Hydrogen sulfide (H 2 S) has been reported to have multiple biological activities. We aim to investigate the role of H 2 S in impaired wound healing in ob/ob mice and explore the possible mechanisms involved. Full-thickness skin dorsal wounds were created on ob/ob mice and C57BL/6 mice. Cystathionine-γ-lyase (CSE) expression and H 2 S production were determined in granulation tissues of the wounds. Effects of NaHS on wound healing were evaluated. Inflammation and angiogenesis in granulation tissues of the wounds were examined. CSE expression, and H 2 S content were significantly reduced in granulation tissues of wounds in ob/ob mice compared with control mice. NaHS treatment significantly improved wound healing in ob/ob mice, which was associated with reduced neutrophil and macrophage infiltration, decreased production of tumor necrosis factor (TNF)-α, interleukin (IL)-6. NaHS treatment decreased metalloproteinase (MMP)-9, whereas increased collagen deposition and vascular-like structures in granulation tissues of wounds in ob/ob mice. CSE down-regulation may play a role in the pathogenesis of diabetic impaired wound healing. Exogenous H 2 S could be a potential agent to improve diabetic impaired wound healing by attenuating inflammation and increasing angiogenesis. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Cadmium-Induced Hydrogen Sulfide Synthesis Is Involved in Cadmium Tolerance in Medicago sativa by Reestablishment of Reduced (Homo)glutathione and Reactive Oxygen Species Homeostases

    PubMed Central

    Cui, Weiti; Chen, Huiping; Zhu, Kaikai; Jin, Qijiang; Xie, Yanjie; Cui, Jin; Xia, Yan; Zhang, Jing; Shen, Wenbiao

    2014-01-01

    Until now, physiological mechanisms and downstream targets responsible for the cadmium (Cd) tolerance mediated by endogenous hydrogen sulfide (H2S) have been elusive. To address this gap, a combination of pharmacological, histochemical, biochemical and molecular approaches was applied. The perturbation of reduced (homo)glutathione homeostasis and increased H2S production as well as the activation of two H2S-synthetic enzymes activities, including L-cysteine desulfhydrase (LCD) and D-cysteine desulfhydrase (DCD), in alfalfa seedling roots were early responses to the exposure of Cd. The application of H2S donor sodium hydrosulfide (NaHS), not only mimicked intracellular H2S production triggered by Cd, but also alleviated Cd toxicity in a H2S-dependent fashion. By contrast, the inhibition of H2S production caused by the application of its synthetic inhibitor blocked NaHS-induced Cd tolerance, and destroyed reduced (homo)glutathione and reactive oxygen species (ROS) homeostases. Above mentioned inhibitory responses were further rescued by exogenously applied glutathione (GSH). Meanwhile, NaHS responses were sensitive to a (homo)glutathione synthetic inhibitor, but reversed by the cotreatment with GSH. The possible involvement of cyclic AMP (cAMP) signaling in NaHS responses was also suggested. In summary, LCD/DCD-mediated H2S might be an important signaling molecule in the enhancement of Cd toxicity in alfalfa seedlings mainly by governing reduced (homo)glutathione and ROS homeostases. PMID:25275379

  7. Sodium hydrosulfide induces systemic thermotolerance to strawberry plants through transcriptional regulation of heat shock proteins and aquaporin

    PubMed Central

    2014-01-01

    Background Temperature extremes represent an important limiting factor to plant growth and productivity. The present study evaluated the effect of hydroponic pretreatment of strawberry (Fragaria x ananassa cv. ‘Camarosa’) roots with an H2S donor, sodium hydrosulfide (NaHS; 100 μM for 48 h), on the response of plants to acute heat shock treatment (42°C, 8 h). Results Heat stress-induced phenotypic damage was ameliorated in NaHS-pretreated plants, which managed to preserve higher maximum photochemical PSII quantum yields than stressed plants. Apparent mitigating effects of H2S pretreatment were registered regarding oxidative and nitrosative secondary stress, since malondialdehyde (MDA), H2O2 and nitric oxide (NO) were quantified in lower amounts than in heat-stressed plants. In addition, NaHS pretreatment preserved ascorbate/glutathione homeostasis, as evidenced by lower ASC and GSH pool redox disturbances and enhanced transcription of ASC (GDH) and GSH biosynthetic enzymes (GS, GCS), 8 h after heat stress imposition. Furthermore, NaHS root pretreatment resulted in induction of gene expression levels of an array of protective molecules, such as enzymatic antioxidants (cAPX, CAT, MnSOD, GR), heat shock proteins (HSP70, HSP80, HSP90) and aquaporins (PIP). Conclusion Overall, we propose that H2S root pretreatment activates a coordinated network of heat shock defense-related pathways at a transcriptional level and systemically protects strawberry plants from heat shock-induced damage. PMID:24499299

  8. Hydrogen Sulfide Improves Endothelial Dysfunction via Downregulating BMP4/COX-2 Pathway in Rats with Hypertension.

    PubMed

    Xiao, Lin; Dong, Jing-Hui; Jin, Sheng; Xue, Hong-Mei; Guo, Qi; Teng, Xu; Wu, Yu-Ming

    2016-01-01

    Aims. We object to elucidate that protective effect of H2S on endothelium is mediated by downregulating BMP4 (bone morphogenetic protein 4)/cyclooxygenase- (COX-) 2 pathway in rats with hypertension. Methods and Results. The hypertensive rat model induced by two-kidney one-clip (2K1C) model was used. Exogenous NaHS administration (56 μmol/kg/day, intraperitoneally once a day) reduced mean arterial pressure (MAP) of 2K1C rats from 199.9 ± 3.312 mmHg to 159.4 ± 5.434 mmHg, while NaHS did not affect the blood pressure in the Sham rats and ameliorated endothelium-dependent contractions (EDCs) of renal artery in 2K1C rats. 2K1C reduced CSE level twofold, decreased plasma levels of H2S about 6-fold, increased BMP4, Nox2, and Nox4 levels 2-fold and increased markers of oxidative stress MDA and nitrotyrosine 1.5-fold, upregulated the expression of phosphorylation-p38 MAPK 2-fold, and increased protein levels of COX-2 1.5-fold, which were abolished by NaHS treatment. Conclusions. Our results demonstrate that H2S prevents activation of BMP4/COX-2 pathway in hypertension, which may be involved in the ameliorative effect of H2S on endothelial impairment. These results throw light on endothelial protective effect of H2S and provide new target for prevention and therapy of hypertension.

  9. Detection and identification of glycoyessotoxin A in a culture of the dinoflagellate Protoceratium reticulatum.

    PubMed

    Paz, Beatriz; Riobó, Pilar; Souto, María L; Gil, Laura V; Norte, Manuel; Fernández, José J; Franco, José M

    2006-11-01

    The toxin composition of a culture of the dinoflagellate Protoceratium reticulatum was investigated using LC-FLD, after derivatization with DMEQ-TAD (4-(2-(6,7-dimethoxy-4-methyl-3-oxo-3,4-dihydroquinoxalimylethyl)-1,2,4-triazoline-3,5-dione)). Besides yessotoxin (YTX), the new YTX analogue, glycoyessotoxin A (G-YTXA) was detected in culture medium as well as in cells. The conditions for extraction were optimized and the production profile established. Retention time of the resulting fluorescent G-YTXA adduct was identified by comparison of the appropriate standard. Additionally, both G-YTXA and the DMEQ-TAD-G-YTXA adduct were confirmed by LC-MS showing ion peaks at m/z 1273 [M-2Na+H](-) and m/z 1618 [M-2Na+H](-), respectively. The LC-MS(n) displayed a fragmentation pattern similar to that of the YTX series.

  10. 78 FR 12794 - Notice of Determinations Regarding Eligibility To Apply for Worker Adjustment Assistance

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-25

    ... Brands Black River, NY.... November 19, 2011. Corporation (IBC), Hostess Brands, Inc. 82,165D Interstate... Verizon Business San Antonio, TX.... Networks Services, Inc., Senior Coordinator-Oder Management, Voice...

  11. Na+-H+ exchange activity in taste receptor cells.

    PubMed

    Vinnikova, Anna K; Alam, Rammy I; Malik, Shahbaz A; Ereso, Glenn L; Feldman, George M; McCarty, John M; Knepper, Mark A; Heck, Gerard L; DeSimone, John A; Lyall, Vijay

    2004-03-01

    mRNA for two Na(+)-H(+)-exchanger isoforms 1 and 3 (NHE-1 and NHE-3) was detected by RT-PCR in fungiform and circumvallate taste receptor cells (TRCs). Anti-NHE-1 antibody binding was localized to the basolateral membranes, and the anti-NHE-3 antibody was localized in the apical membranes of fungiform and circumvallate TRCs. In a subset of TRCs, NHE-3 immunoreactivity was also detected in the intracellular compartment. For functional studies, an isolated lingual epithelium containing a single fungiform papilla was mounted with apical and basolateral sides isolated and perfused with nominally CO(2)/HCO(3)(-)-free physiological media (pH 7.4). The TRCs were monitored for changes in intracellular pH (pH(i)) and Na(+) ([Na(+)](i)) using fluorescence ratio imaging. At constant external pH, 1) removal of basolateral Na(+) reversibly decreased pH(i) and [Na(+)](i); 2) HOE642, a specific blocker, and amiloride, a nonspecific blocker of basolateral NHE-1, attenuated the decrease in pH(i) and [Na(+)](i); 3) exposure of TRCs to basolateral NH(4)Cl or sodium acetate pulses induced transient decreases in pH(i) that recovered spontaneously to baseline; 4) pH(i) recovery was inhibited by basolateral amiloride, 5-(N-methyl-N-isobutyl)-amiloride (MIA), 5-(N-ethyl-N-isopropyl)-amiloride (EIPA), HOE642, and by Na(+) removal; 5) HOE642, MIA, EIPA, and amiloride inhibited pH(i) recovery with K(i) values of 0.23, 0.46, 0.84, and 29 microM, respectively; and 6) a decrease in apical or basolateral pH acidified TRC pH(i) and inhibited spontaneous pH(i) recovery. The results indicate the presence of a functional NHE-1 in the basolateral membranes of TRCs. We hypothesize that NHE-1 is involved in sour taste transduction since its activity is modulated during acid stimulation.

  12. Interaction between endogenous carbon monoxide and hydrogen sulfide in the mechanism of gastroprotection against acute aspirin-induced gastric damage.

    PubMed

    Magierowski, Marcin; Magierowska, Katarzyna; Hubalewska-Mazgaj, Magdalena; Adamski, Juliusz; Bakalarz, Dominik; Sliwowski, Zbigniew; Pajdo, Robert; Kwiecien, Slawomir; Brzozowski, Tomasz

    2016-12-01

    Acetylsalicylic acid (ASA) is mainly recognized as painkiller or anti-inflammatory drug. However, ASA causes serious side effects towards gastrointestinal (GI) tract which limits its usefulness. Carbon monoxide (CO) and hydrogen sulfide (H 2 S) have been described to act as important endogenous messengers and mediators of gastroprotection but whether they can interact in gastroprotection against acute ASA-induced gastric damage remains unknown. In this study male Wistar rats were pretreated with 1) vehicle (saline, i.g.), 2) tricarbonyldichlororuthenium (II) dimer (CORM-2, 5mg/kg i.g.), 3) sodium hydrosulfide (NaHS, 5mg/kg i.g.), 4) zinc protoporphyrin (ZnPP, 10mg/kg i.p.), 5) D,L-propargylglycine (PAG, 30mg/kg i.g.), 6) ZnPP combined with NaHS, 7) PAG combined with CORM-2 or 8) 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 10mg/kg i.p.) combined with CORM-2 or NaHS and 30min later ASA was administered i.g. in a single dose of 125mg/kg. After 1h, gastric blood flow (GBF) was determined by H 2 gas clearance technique and gastric lesions were assessed by planimetry and histology. CO content in gastric mucosa and COHb concentration in blood were determined by gas chromatography and H 2 S production was assessed in gastric mucosa using methylene blue method. Protein and/or mRNA expression for cystathionine-γ-lyase (CSE), cystathionine-β-synthase (CBS), 3-mercaptopyruvate sulfurtransferase (3-MST), heme oxygenase (HO)-1, HO-2, hypoxia inducible factor-alpha (HIF)-1α, nuclear factor (erythroid-derived 2)-like 2 (Nrf-2), cyclooxygenase (COX)-1 and COX-2, inducible nitric oxide synthase (iNOS) and interleukin (IL)-1β were determined by Western blot or real-time PCR, respectively. ASA caused hemorrhagic gastric mucosal damage and significantly decreased GBF, H 2 S production, CO content, mRNA or protein expression for CSE, 3-MST, HO-2 and increased mRNA and/or protein expression for CBS, HO-1, Nrf-2, HIF-1α, iNOS, IL-1β, COX-2 in gastric mucosa and COHb

  13. Extrusion & Compoundierung

    NASA Astrophysics Data System (ADS)

    Collin, Heinz; Schulze, Verena

    Unter Extrusion wird das kontinuierliche Fördern von formbaren Massen verstanden. Dies können Kunststoffe, Teigwaren in der Lebensmittelindustrie oder auch keramische Massen sein. In der chemischen Industrie werden ebenfalls hochviskose (schwerfließende) Stoffe oder Pasten dosiert, gefördert und extrudiert. Früher waren vorzugsweise Kolbenstrangpressen im Einsatz, bis sich ab 1950 in steigendem Maße die Schneckenmaschinen durchgesetzt haben. Der weltweite Siegeszug der Kunststoffe ist zu einem erheblichen Teil auf die stetige technologische Weiterentwicklung im Bereich der Extrusionstechnik zurückzuführen. Der Markt der weltweit produzierten Maschinen für die Kunststoffverarbeitung erreichte im Jahr 2006 einen Wert von 20 Milliarden Euro und somit zählt dieser Bereich mittlerweile zu einem der großen Industriezweige [1].

  14. Identification of New World Quails Susceptible to Infection with Avian Leukosis Virus Subgroup J

    PubMed Central

    Plachý, Jiří; Reinišová, Markéta; Kučerová, Dana; Šenigl, Filip; Stepanets, Volodymyr; Hron, Tomáš; Trejbalová, Kateřina; Elleder, Daniel

    2016-01-01

    ABSTRACT The J subgroup of avian leukosis virus (ALV-J) infects domestic chickens, jungle fowl, and turkeys. This virus enters the host cell through a receptor encoded by the tvj locus and identified as Na+/H+ exchanger 1. The resistance to avian leukosis virus subgroup J in a great majority of galliform species has been explained by deletions or substitutions of the critical tryptophan 38 in the first extracellular loop of Na+/H+ exchanger 1. Because there are concerns of transspecies virus transmission, we studied natural polymorphisms and susceptibility/resistance in wild galliforms and found the presence of tryptophan 38 in four species of New World quails. The embryo fibroblasts of New World quails are susceptible to infection with avian leukosis virus subgroup J, and the cloned Na+/H+ exchanger 1 confers susceptibility on the otherwise resistant host. New World quails are also susceptible to new avian leukosis virus subgroup J variants but resistant to subgroups A and B and weakly susceptible to subgroups C and D of avian sarcoma/leukosis virus due to obvious defects of the respective receptors. Our results suggest that the avian leukosis virus subgroup J could be transmitted to New World quails and establish a natural reservoir of circulating virus with a potential for further evolution. IMPORTANCE Since its spread in broiler chickens in China and Southeast Asia in 2000, ALV-J remains a major enzootic challenge for the poultry industry. Although the virus diversifies rapidly in the poultry, its spillover and circulation in wild bird species has been prevented by the resistance of most species to ALV-J. It is, nevertheless, important to understand the evolution of the virus and its potential host range in wild birds. Because resistance to avian retroviruses is due particularly to receptor incompatibility, we studied Na+/H+ exchanger 1, the receptor for ALV-J. In New World quails, we found a receptor compatible with virus entry, and we confirmed the

  15. APPLICATIONS FOR DNA PROBES IN BIODEGRADATION RESEARCH

    EPA Science Inventory

    The use of DNA:DNA hybridization technology in biodegradation studies is investigated. The rate constants for sediments exposed to synthetic oils could be calculated from the NAH(1+) genotypes and this approach would be useful in predicting the kinetics of aromatic hydrocarbon de...

  16. Erhöhtes Lungenkrebs-Risiko bei Ekzempatienten: eine landesweite Kohortenstudie in Taiwan.

    PubMed

    Juan, Chao-Kuei; Shen, Jui-Lung; Lin, Cheng-Li; Kim, Karen Wang; Chen, Wen-Chi

    2016-09-01

    Der Zusammenhang zwischen Lungenkrebs und Ekzemen bleibt umstritten. Frühere Studien haben zu widersprüchlichen Ergebnissen geführt. Diese retrospektive populationsbasierte Kohortenstudie zielt darauf ab, das Risiko von Lungenkrebs im Zusammenhang mit Ekzemen abzuklären. In der Forschungsdatenbank der taiwanesischen nationalen Krankenversicherung identifizierten wir 43719 Patienten, bei denen in den Jahren 2000 bis 2010 ein Ekzem neu diagnostiziert wurde. Die Vergleichskohorte bildeten 87438 zufällig ausgewählte, altersangepasste Patienten ohne Ekzem. Die Fälle aus diesen beiden Kohorten wurden bis 2011 verfolgt. Zur Kalkulation des Lungenkrebsrisikos bei Ekzempatienten wurde die Cox-Regression verwendet. Die Datenbank enthielt keine Informationen über Raucherstatus, Alkoholkonsum, sozioökonomischen Status oder Familienanamnese. Nach der Bereinigung um Alter und Komorbidität hatte die Population mit Ekzemen ein um 2,80 erhöhtes Risiko für die Entwicklung von Lungenkrebs gegenüber der Vergleichskohorte (bereinigte Hazard-Ratio 2,80, 95 % Konfidenzinterval 2,59-3,03). Ekzempatienten mit Begleiterkrankungen, darunter Asthma, chronisch obstruktive Lungenerkrankungen, alkoholbedingten Leberschäden oder Diabetes, hatten ein höheres Lungenkrebsrisiko als Patienten ohne Ekzeme oder Komorbidität. Ekzeme gehen mit einem höheren Risiko für die Entwicklung von Lungenkrebs einher. Weitere Studien mit umfassenderen Informationen über weitere potentielle Einflussfaktoren sind sinnvoll. © 2016 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

  17. Distribution of hydrogen sulfide (H₂S)-producing enzymes and the roles of the H₂S donor sodium hydrosulfide in diabetic nephropathy.

    PubMed

    Yamamoto, Junichiro; Sato, Waichi; Kosugi, Tomoki; Yamamoto, Tokunori; Kimura, Toshihide; Taniguchi, Shigeki; Kojima, Hiroshi; Maruyama, Shoichi; Imai, Enyu; Matsuo, Seiichi; Yuzawa, Yukio; Niki, Ichiro

    2013-02-01

    Hydrogen sulfide (H(2)S) has recently been found to play beneficial roles in ameliorating several diseases, including hypertension, atherosclerosis and cardiac/renal ischemia-reperfusion injuries. Cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE), the main enzymes in the transsulfuration pathway, catalyze H(2)S production in mammalian tissues. However, the distributions and precise roles of these enzymes in the kidney have not yet been identified. The present study examined the localization of both enzymes in the normal kidney and the effect of the H(2)S donor sodium hydrosulfide (NaHS) in the renal peritubular capillary (PTC) under conditions of diabetic nephropathy, using pancreatic β-cell-specific calmodulin-overexpressing transgenic mice as a model of diabetes. In the normal kidney, we detected expression of both CBS and CSE in the brush border and cytoplasm of the proximal tubules, but not in the glomeruli, distal tubules and vascular endothelial cells of renal PTCs. Administration of NaHS increased PTC diameter and blood flow. We further evaluated whether biosynthesis of H(2)S was altered in a spontaneous diabetic model that developed renal lesions similar to human diabetic nephropathy. CSE expression was markedly reduced under diabetic conditions, whereas CBS expression was unaffected. Progressive diabetic nephropathy showed vasoconstriction and a loss of blood flow in PTCs that was ameliorated by NaHS treatment. These findings suggest that CSE expression in the proximal tubules may also regulate tubulointerstitial microcirculation via H(2)S production. H(2)S may represent a target of treatment to prevent progression of ischemic injury in diabetic nephropathy.

  18. Hydrogen sulfide-induced itch requires activation of Cav3.2 T-type calcium channel in mice

    PubMed Central

    Wang, Xue-Long; Tian, Bin; Huang, Ya; Peng, Xiao-Yan; Chen, Li-Hua; Li, Jun-Cheng; Liu, Tong

    2015-01-01

    The contributions of gasotransmitters to itch sensation are largely unknown. In this study, we aimed to investigate the roles of hydrogen sulfide (H2S), a ubiquitous gasotransmitter, in itch signaling. We found that intradermal injection of H2S donors NaHS or Na2S, but not GYY4137 (a slow-releasing H2S donor), dose-dependently induced scratching behavior in a μ-opioid receptor-dependent and histamine-independent manner in mice. Interestingly, NaHS induced itch via unique mechanisms that involved capsaicin-insensitive A-fibers, but not TRPV1-expressing C-fibers that are traditionally considered for mediating itch, revealed by depletion of TRPV1-expressing C-fibers by systemic resiniferatoxin treatment. Moreover, local application of capsaizapine (TRPV1 blocker) or HC-030031 (TRPA1 blocker) had no effects on NaHS-evoked scratching. Strikingly, pharmacological blockade and silencing of Cav3.2 T-type calcium channel by mibefradil, ascorbic acid, zinc chloride or Cav3.2 siRNA dramatically decreased NaHS-evoked scratching. NaHS induced robust alloknesis (touch-evoked itch), which was inhibited by T-type calcium channels blocker mibefradil. Compound 48/80-induced itch was enhanced by an endogenous precursor of H2S (L-cysteine) but attenuated by inhibitors of H2S-producing enzymes cystathionine γ-lyase and cystathionine β-synthase. These results indicated that H2S, as a novel nonhistaminergic itch mediator, may activates Cav3.2 T-type calcium channel, probably located at A-fibers, to induce scratching and alloknesis in mice. PMID:26602811

  19. [Degradation characteristics of naphthalene with a Pseudomonas aeruginosa strain isolated from soil contaminated by diesel].

    PubMed

    Liu, Wen-Chao; Wu, Bin-Bin; Li, Xiao-Sen; Lu, Dian-Nan; Liu, Yong-Min

    2015-02-01

    Abstract: A naphthalene-degrading bacterium (referred as HD-5) was isolated from the diesel-contaminated soil and was assigned to Pseudomonas aeruginosa according to 16S rDNA sequences analysis. Gene nah, which encodes naphthalene dioxygenase, was identified from strain HD-5 by PCR amplification. Different bioremediation approaches, including nature attenuation, bioaugmentation with strain Pseudomonas aeruginosa, biostimulation, and an integrated degradation by bioaugmentation and biostimulation, were evaluated for their effectiveness in the remediating soil containing 5% naphthalene. The degradation rates of naphthalene in the soil were compared among the different bioremediation approaches, the FDA and dehydrogenase activity in bioremediation process were measured, and the gene copy number of 16S rRNA and nah in soil were dynamically monitored using real-time PCR. It was shown that the naphthalene removal rate reached 71.94%, 62.22% and 83.14% in approaches of bioaugmentation (B), biostimulation(S) and integrated degradation composed of bioaugmentation and biostimulation (BS), respectively. The highest removal rate of naphthalene was achieved by using BS protocol, which also gives the highest FDA and dehydrogenase activity. The gene copy number of 16S rRNA and nah in soil increased by about 2.67 x 10(11) g(-1) and 8.67 x 10(8) g(-1) after 31 days treatment using BS protocol. Above-mentioned results also demonstrated that the screened bacterium, Pseudomonas aeruginosa, could grow well in naphthalene-contaminated soil and effectively degrade naphthalene, which is of fundamental importance for bioremediation of naphthalene-contaminated soil.

  20. Hydrogen Sulfide Up-Regulates the Expression of ATP-Binding Cassette Transporter A1 via Promoting Nuclear Translocation of PPARα.

    PubMed

    Li, Dong; Xiong, Qinghui; Peng, Jin; Hu, Bin; Li, Wanzhen; Zhu, Yizhun; Shen, Xiaoyan

    2016-04-29

    ATP binding cassette transporter A1 (ABCA1) plays a key role in atherogenesis. Hydrogen sulfide (H₂S), a gasotransmitter, has been reported to play an anti-atherosclerotic role. However, the underlying mechanisms are largely unknown. In this study we examined whether and how H₂S regulates ABCA1 expression. The effect of H₂S on ABCA1 expression and lipid metabolism were assessed in vitro by cultured human hepatoma cell line HepG2, and in vivo by ApoE(-/-) mice with a high-cholesterol diet. NaHS (an exogenous H₂S donor) treatment significantly increased the expression of ABCA1, ApoA1, and ApoA2 and ameliorated intracellular lipid accumulation in HepG2 cells. Depletion of the endogenous H₂S generator cystathionine γ-lyase (CSE) by small RNA interference (siRNA) significantly decreased the expression of ABCA1 and resulted in the accumulation of lipids in HepG2 cells. In vivo NaHS treatment significantly reduced the serum levels of total cholesterol (TC), triglycerides (TG), and low-density lipoproteins (LDL), diminished atherosclerotic plaque size, and increased hepatic ABCA1 expression in fat-fed ApoE(-/-) mice. Further study revealed that NaHS upregulated ABCA1 expression by promoting peroxisome proliferator-activated receptor α (PPARα) nuclear translocation. H₂S up-regulates the expression of ABCA1 by promoting the nuclear translocation of PPARα, providing a fundamental mechanism for the anti-atherogenic activity of H₂S. H₂S may be a promising potential drug candidate for the treatment of atherosclerosis.

  1. Microbial characterization and hydrocarbon biodegradation potential of natural bilge waste microflora.

    PubMed

    Olivera, N L; Commendatore, M G; Delgado, O; Esteves, J L

    2003-09-01

    Shipping operations produce oily wastes that must be managed properly to avoid environmental pollution. The aim of this study was to characterize microorganisms occurring in ship bilge wastes placed in open lagoons and, particularly, to assess their potential to degrade polycyclic aromatic hydrocarbons (PAHs). A first-order kinetic was suitable for describing hydrocarbon biodegradation after 17 days of treatment. The calculated rate constants were 0.0668 and 0.0513 day(-1) with a corresponding half-life of 10.3 and 13.5 days for the aliphatic and aromatic hydrocarbon fractions, respectively. At day 17, PAH removal percentages were: acenaphtylene 100, fluorene 95.2, phenanthrene 93.6, anthracene 70.3, and pyrene 71.5. Methyl phenanthrene removals were lower than that of their parent compound (3-methyl phenanthrene 83.6, 2-methyl phenanthrene 80.8, 1-methyl phenanthrene 77.3, 9-methyl phenanthrene 75.1, and 2,7-dimethyl phenanthrene 76.6). Neither pure cultures nor the microbial community from these wastes showed extracellular biosurfactant production suggesting that the addition of an exogenously produced biosurfactant may be important in enhancing hydrocarbon bioavailability and biodegradation. DNA analysis of bilge waste samples revealed a ubiquitous distribution of the nahAc genotype in the dump pools. Although almost all of the isolates grew on naphthalene as sole carbon source, only some of them yielded nahAc amplification under the experimental conditions used. The variety of PAHs in bilge wastes could support bacteria with multiple degradation pathways and a diversity of catabolic genes divergent from the classical nah-like type.

  2. Proximal tubule hydrogen ion transport processes in diuretic-induced metabolic alkalosis.

    PubMed

    Blumenthal, S S; Ware, R A; Kleinman, J G

    1985-07-01

    Transport systems involved in proximal tubule HCO-3 reabsorption were examined in disaggregated renal cortical tubules from rabbits with metabolic alkalosis. The acid-base disorder was induced by first treating the animals with furosemide, and then maintaining them on low Cl--high HCO-3 diets. On this regimen, the rabbits had increases in blood pH and total CO2 values and decreases in serum K+ concentrations. Urine Cl- concentrations were less than 15 mEq/L in all cases. Na+-H+ exchange was evaluated by incubating tubules in rotenone in an Na+-free medium to deplete them of Na+ and adenosine triphosphate. Then the tubules were resuspended in media containing 65 or 12.5 mEq/L Na+ at either pH 7.1 or pH 7.6. The rise in cell pH estimated by dimethadione distribution was taken as a measure of Na+-H+ exchanger activity. At the high incubation pH, Na+-H+ exchanger activity appeared to be the same in tubules taken from alkalotic rabbits compared with those prepared from normal rabbits. At the low incubation pH, the activity of this transport system appeared to be depressed by 40% to 50% in alkalosis, with kinetics that suggested a decreased Vmax for the exchanger. Na+-independent H+ transport, presumably reflecting activity of an H+-adenosine triphosphatase, was evaluated by preincubating tubules in a Na+-free medium in the presence of ouabain, and then sequentially exposing them to and removing them from a solution containing 20 mmol/L NH4Cl.(ABSTRACT TRUNCATED AT 250 WORDS)

  3. Salicylic acid is an indispensable component of the Ny-1 resistance-gene-mediated response against Potato virus Y infection in potato

    PubMed Central

    Baebler, Š.; Witek, K.; Gruden, K.; Hennig, J.

    2014-01-01

    The purpose of the study was to investigate the role of salicylic acid (SA) signalling in Ny-1-mediated hypersensitive resistance (HR) of potato (Solanum tuberosum L.) to Potato virus Y (PVY). The responses of the Ny-1 allele in the Rywal potato cultivar and transgenic NahG-Rywal potato plants that do not accumulate SA were characterized at the cytological, biochemical, transcriptome, and proteome levels. Analysis of noninoculated and inoculated leaves revealed that HR lesions started to develop from 3 d post inoculation and completely restricted the virus spread. At the cytological level, features of programmed cell death in combination with reactive oxygen species burst were observed. In response to PVY infection, SA was synthesized de novo. The lack of SA accumulation in the NahG plants led to the disease phenotype due to unrestricted viral spreading. Grafting experiments show that SA has a critical role in the inhibition of PVY spreading in parenchymal tissue, but not in vascular veins. The whole transcriptome analysis confirmed the central role of SA in orchestrating Ny-1-mediated responses and showed that the absence of SA leads to significant changes at the transcriptome level, including a delay in activation of expression of genes known to participate in defence responses. Moreover, perturbations in the expression of hormonal signalling genes were detected, shown as a switch from SA to jasmonic acid/ethylene signalling. Viral multiplication in the NahG plants was accompanied by downregulation of photosynthesis genes and activation of multiple energy-producing pathways. PMID:24420577

  4. Effects of different agricultural wastes on the dissipation of PAHs and the PAH-degrading genes in a PAH-contaminated soil.

    PubMed

    Han, Xuemei; Hu, Hangwei; Shi, Xiuzhen; Zhang, Limei; He, Jizheng

    2017-04-01

    Land application of agricultural wastes is considered as a promising bioremediation approach for cleaning up soils contaminated by aged polycyclic aromatic hydrocarbons (PAHs). However, it remains largely unknown about how microbial PAH-degraders, which play a key role in the biodegradation of soil PAHs, respond to the amendments of agricultural wastes. Here, a 90-day soil microcosm study was conducted to compare the effects of three agricultural wastes (i.e. WS, wheat stalk; MCSW, mushroom cultivation substrate waste; and CM, cow manure) on the dissipation of aged PAHs and the abundance and community structure of PAH-degrading microorganisms. The results showed that all the three agricultural wastes accelerated the dissipation of aged PAHs and significantly increased abundances of the bacterial 16S rRNA and PAH-degrading genes (i.e. pdo1 and nah). CM and MCSW with lower ratios of C:N eliminated soil PAHs more efficiently than WS with a high ratio of C:N. Low molecular weight PAHs were dissipated more quickly than those with high molecular weight. Phylogenetic analysis revealed that all of the nah and C12O clones were affiliated within Betaproteobacteria and Gammaproteobacteria, and application of agricultural wastes significantly changed the community structure of the microorganisms harboring nah and C12O genes, particularly in the CM treatment. Taken together, our findings suggest that the three tested agricultural wastes could accelerate the degradation of aged PAHs most likely through changing the abundances and community structure of microbial PAH degraders. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Salicylic acid is an indispensable component of the Ny-1 resistance-gene-mediated response against Potato virus Y infection in potato.

    PubMed

    Baebler, Š; Witek, K; Petek, M; Stare, K; Tušek-Žnidarič, M; Pompe-Novak, M; Renaut, J; Szajko, K; Strzelczyk-Żyta, D; Marczewski, W; Morgiewicz, K; Gruden, K; Hennig, J

    2014-03-01

    The purpose of the study was to investigate the role of salicylic acid (SA) signalling in Ny-1-mediated hypersensitive resistance (HR) of potato (Solanum tuberosum L.) to Potato virus Y (PVY). The responses of the Ny-1 allele in the Rywal potato cultivar and transgenic NahG-Rywal potato plants that do not accumulate SA were characterized at the cytological, biochemical, transcriptome, and proteome levels. Analysis of noninoculated and inoculated leaves revealed that HR lesions started to develop from 3 d post inoculation and completely restricted the virus spread. At the cytological level, features of programmed cell death in combination with reactive oxygen species burst were observed. In response to PVY infection, SA was synthesized de novo. The lack of SA accumulation in the NahG plants led to the disease phenotype due to unrestricted viral spreading. Grafting experiments show that SA has a critical role in the inhibition of PVY spreading in parenchymal tissue, but not in vascular veins. The whole transcriptome analysis confirmed the central role of SA in orchestrating Ny-1-mediated responses and showed that the absence of SA leads to significant changes at the transcriptome level, including a delay in activation of expression of genes known to participate in defence responses. Moreover, perturbations in the expression of hormonal signalling genes were detected, shown as a switch from SA to jasmonic acid/ethylene signalling. Viral multiplication in the NahG plants was accompanied by downregulation of photosynthesis genes and activation of multiple energy-producing pathways.

  6. Annual Letter Report on ONR (Office of Naval Research) Contract Number N00014-85-K-0228.

    DTIC Science & Technology

    1985-12-02

    olefination, ".. and thioketalization, are currently under way. Stabilization of these polyketones _ with respect to aldolization is particularly important for...11 NaH High Dilution 67 ..- expected that a knotted polyketone will be especially prone to intramolecular trans-annular reactions. The four-rung THYME

  7. Antimicrobial resistance of Salmonella enterica isolates from bulk tank milk and milk filters in the United States

    USDA-ARS?s Scientific Manuscript database

    Non-typhoid Salmonella is frequently associated with dairy cattle and their environment. Despite well-developed milking hygiene protocols, fecal contamination can occur and Salmonella has often been isolated from bulk milk. Salmonella isolates were recovered from US bulk tank milk as part of the NAH...

  8. Enhanced tolerance to NaC1 and LiC1 stresses by over-expressing Caragana korshinskii sodium/proton exchange 1 (CkNHX1) and the hydrophilic C terminus is required for the activity of CkNHX1 in Atsos3-1 mutant and yeast

    USDA-ARS?s Scientific Manuscript database

    Sodium/proton exchangers (NHX antiporters) play important roles in plant responses to salt stress. Previous research showed that hydrophilic C-terminal region of Arabidopsis AtNHX1 negatively regulates the Na+/H+ transporting activity. In this study, CkNHX1 were isolated from Caragana korshinskii,...

  9. Riparian landscapes: Linking geodiversity with habitat and biodiversity

    NASA Astrophysics Data System (ADS)

    Chmieleski, Jana; Danzeisen, Laura

    2017-04-01

    Keywords: Oder valley, biodiversity, geodiversity River landscapes of all scales originally showed a high diversity of structures and habitats at a small spatial entity, such as the stream beds, terrasses, sand and gravel banks. This variety, with a lot of different elements, patches and patterns, represents not only a variety of geoelements or geomorhological features but also a large biodiversity, both of habitats and species. Riparian landscapes are both, a natural as well as a geoheritage, often even a cultural heritage (sustainabe land use practices). Embankments, utilization for agriculture, constructions for navigation, management measures lead to a strong loss of these structures. This impacts the value of the landscape as well ecosystem functions, not only the biodiversity and the geodiversity but also the recreation function or the aesthetic values. A case study from the National Park Lower Oder Valley in the Northeastern part of Germany, wich is also part of a Geopark („Eiszeitland am Oderrand") presents the connections of the diversity of geomorphological features with biodiversity and shows the loss of features (loss of values) due to intensive utilisation by using GIS-analysis and landscape-metrics. The Northern part of the Oder valley (National Park, transnational protection area of Germany and Poland) have been modified by man since centuries but even so remained in near-natural state that allows semi-(natural) stream dynamics. While the Oder's reparian zone is marked by the stream itself, by its bayous, reed beds, periodically flooded wet meadows and by its natural riparian forest the mineral morainic plateaus are marked by semi-natural forests and dry grasslands. Two areas of different degradation states, a) near-natural and wilderness area and b) grassland area will be compared in order to identify: quantity and extent of features, relation of measure and coverage, connectivity with other features, quantity and types of habitats (with

  10. Die Struktur von schlankem Materialfluss mit Lean Production Kanban und Innovationen

    NASA Astrophysics Data System (ADS)

    Scheid, Wolf-Michael

    In der Literatur wird Materialfluss überwiegend in Spezialdisziplinen betrachtet, etwa der Steuerungslogik, der Logistiktechnik oder dem Supply Chain Management. Ein charakterisierendes Merkmal des Materialflusses ist jedoch, dass er sich aus vielfältigen Einzelbausteinen zusammensetzt, die alle harmonisch abgestimmt sein müssen. Die maximal erreichbare Effizienz wird nicht durch Höchstleistungen in dem einen oder anderen Spezialthema bestimmt, sondern durch das schwächste Glied im gesamten komplexen Netzwerk. Den Schnittstellen zwischen den betroffenen Fachbereichen in einem Unternehmen kommt hier eine ganz besondere Bedeutung zu: Erst ein harmonischer Einklang ermöglicht hohe Effektivität. Dies setzt umfassendes Verständnis für interdisziplinäre Notwendigkeiten, ein hohes Maß an Abstimmung mit den operativen Prozessen und letztlich einen einvernehmlichen Umgang und den Respekt vor den Problemstellungen des Anderen voraus.

  11. Experimental study using Nearfield Acoustical Holography of sound transmission fuselage sidewall structures

    NASA Technical Reports Server (NTRS)

    Maynard, J. D.

    1983-01-01

    This project involves the development of the Nearfield Acoustic Holography (NAH) technique (in particular its extension from single frequency to wideband noise measurement) and its application in a detailed study of the noise radiation characteristics of several samples of aircraft sidewall panels. With the extensive amount of information provided by the NAH technique, the properties of the sound field radiated by the panels may be correlated with their structure, mounting, and excitation (single frequency or wideband, spatially correlated or uncorrelated, structure-borne). The work accomplished at the beginning of this grant period included: (1) Calibration of the 256 microphone array and test of its accuracy. (2) extension of the facility to permit measurements on wideband noise sources. The extensions incuded the addition of high-speed data acquisition hardware and an array processor, and the development of new software. (3) Installation of motion picture graphics for correlating panel motion with structure, mounting, radiation, etc. (4) Development of new holographic data processing techniques.

  12. Energy conservation by oxidation of formate to carbon dioxide and hydrogen via a sodium ion current in a hyperthermophilic archaeon

    PubMed Central

    Lim, Jae Kyu; Mayer, Florian; Kang, Sung Gyun; Müller, Volker

    2014-01-01

    Thermococcus onnurineus NA1 is known to grow by the anaerobic oxidation of formate to CO2 and H2, a reaction that operates near thermodynamic equilibrium. Here we demonstrate that this reaction is coupled to ATP synthesis by a transmembrane ion current. Formate oxidation leads to H+ translocation across the cytoplasmic membrane that then drives Na+ translocation. The ion-translocating electron transfer system is rather simple, consisting of only a formate dehydrogenase module, a membrane-bound hydrogenase module, and a multisubunit Na+/H+ antiporter module. The electrochemical Na+ gradient established then drives ATP synthesis. These data give a mechanistic explanation for chemiosmotic energy conservation coupled to formate oxidation to CO2 and H2. Because it is discussed that the membrane-bound hydrogenase with the Na+/H+ antiporter module are ancestors of complex I of mitochondrial and bacterial electron transport these data also shed light on the evolution of ion transport in complex I-like electron transport chains. PMID:25049407

  13. Energy conservation by oxidation of formate to carbon dioxide and hydrogen via a sodium ion current in a hyperthermophilic archaeon.

    PubMed

    Lim, Jae Kyu; Mayer, Florian; Kang, Sung Gyun; Müller, Volker

    2014-08-05

    Thermococcus onnurineus NA1 is known to grow by the anaerobic oxidation of formate to CO2 and H2, a reaction that operates near thermodynamic equilibrium. Here we demonstrate that this reaction is coupled to ATP synthesis by a transmembrane ion current. Formate oxidation leads to H(+) translocation across the cytoplasmic membrane that then drives Na(+) translocation. The ion-translocating electron transfer system is rather simple, consisting of only a formate dehydrogenase module, a membrane-bound hydrogenase module, and a multisubunit Na(+)/H(+) antiporter module. The electrochemical Na(+) gradient established then drives ATP synthesis. These data give a mechanistic explanation for chemiosmotic energy conservation coupled to formate oxidation to CO2 and H2. Because it is discussed that the membrane-bound hydrogenase with the Na(+)/H(+) antiporter module are ancestors of complex I of mitochondrial and bacterial electron transport these data also shed light on the evolution of ion transport in complex I-like electron transport chains.

  14. Annual Report of the Chief, National Guard Bureau for the Fiscal Year 1970

    DTIC Science & Technology

    1970-06-30

    visited were Alpena . Michigan and Savan- nah, Georgia. National Guard Bureau CEMT surveys of field training sites will be performed on a continuing basis...this training will be acquired and maintained at the ANC Field Training Site. Alpena , Michigan. Survival radios (ACR/RT-10) continue to be in

  15. Incidental Learning in 3D Virtual Environments: Relationships to Learning Style, Digital Literacy and Information Display

    ERIC Educational Resources Information Center

    Thomas, Wayne W.; Boechler, Patricia M.

    2014-01-01

    With teachers taking more interest in utilizing 3D virtual environments for educational purposes, research is needed to understand how learners perceive and process information within virtual environments (Eschenbrenner, Nah, & Siau, 2008). In this study, the authors sought to determine if learning style or digital literacy predict incidental…

  16. Genetic analysis of salt tolerance in Arabidopsis: Evidence for the role of Ca(2+)/H(+) transporter CAX1

    USDA-ARS?s Scientific Manuscript database

    Coordinate regulation of transporters at both the plasma membrane and vacuole contribute to plant cell's ability to adapt to a changing environment and play a key role in the maintenance of the chemiosmotic circuits required for cellular growth. The plasma membrane (PM) Na+/H+ antiporter SOS1 is inv...

  17. Educator Perspectives on Indigenous Cultural Content in an Occupational Therapy Curriculum

    ERIC Educational Resources Information Center

    Melchert, Belinda; Gray, Marion; Miller, Adrian

    2016-01-01

    Health professionals must understand Indigenous perspectives to deliver effective health services. This study set out to determine the amount, type and effectiveness of current Indigenous content in an occupational therapy curriculum at an Australian regional university and the progress in meeting the National Aboriginal Health Strategy (NAHS)…

  18. Congenital Sodium Diarrhea: A Form of Intractable Diarrhea, With a Link to Inflammatory Bowel Disease.

    PubMed

    Janecke, Andreas R; Heinz-Erian, Peter; Müller, Thomas

    2016-08-01

    Congenital diarrheal disorders (CDDs) represent a group of challenging clinical conditions for pediatricians because of the severity of the presentation and the broad range of possible differential diagnoses. CDDs arise from alterations in the transport of nutrients and electrolytes across the intestinal mucosa, from enterocyte and enteroendocrine cell differentiation and/or polarization defects, and from the modulation of the intestinal immune response. Advances were made recently in deciphering the etiology and pathophysiology of one of these disorders, congenital sodium diarrhea (CSD). CSD refers to an intractable diarrhea of intrauterine onset with high fecal sodium loss. CSD is clinically and genetically heterogeneous. A syndromic form of CSD features choanal and intestinal atresias as well as recurrent corneal erosions. Small bowel histology frequently detects an epithelial "tufting" dysplasia. It is autosomal recessively inherited, and caused by SPINT2 mutations. The nonsyndromic form of CSD can be caused by dominant activating mutations in GUCY2C, encoding intestinal receptor guanylate cyclase C (GC-C), and by autosomal recessive SLC9A3 loss-of-function mutations. SLC9A3 encodes Na/H antiporter 3, the major intestinal brush border Na/H exchanger, and a downstream target of GC-C. A number of patients with GUCY2C and SLC9A3 mutations developed inflammatory bowel disease. Both the number of recognized CDD forms as well as the number of underlying disease genes are gradually increasing. Knowledge of these CDD genes enables noninvasive, next-generation gene panel-based testing to facilitate an early diagnosis in CDD. Primary Na/H antiporter 3 and GC-C malfunction is implicated as a predisposition for inflammatory bowel disease in subset of patients.

  19. Hydrogen Sulfide Up-Regulates the Expression of ATP-Binding Cassette Transporter A1 via Promoting Nuclear Translocation of PPARα

    PubMed Central

    Li, Dong; Xiong, Qinghui; Peng, Jin; Hu, Bin; Li, Wanzhen; Zhu, Yizhun; Shen, Xiaoyan

    2016-01-01

    ATP binding cassette transporter A1 (ABCA1) plays a key role in atherogenesis. Hydrogen sulfide (H2S), a gasotransmitter, has been reported to play an anti-atherosclerotic role. However, the underlying mechanisms are largely unknown. In this study we examined whether and how H2S regulates ABCA1 expression. The effect of H2S on ABCA1 expression and lipid metabolism were assessed in vitro by cultured human hepatoma cell line HepG2, and in vivo by ApoE−/− mice with a high-cholesterol diet. NaHS (an exogenous H2S donor) treatment significantly increased the expression of ABCA1, ApoA1, and ApoA2 and ameliorated intracellular lipid accumulation in HepG2 cells. Depletion of the endogenous H2S generator cystathionine γ-lyase (CSE) by small RNA interference (siRNA) significantly decreased the expression of ABCA1 and resulted in the accumulation of lipids in HepG2 cells. In vivo NaHS treatment significantly reduced the serum levels of total cholesterol (TC), triglycerides (TG), and low-density lipoproteins (LDL), diminished atherosclerotic plaque size, and increased hepatic ABCA1 expression in fat-fed ApoE−/− mice. Further study revealed that NaHS upregulated ABCA1 expression by promoting peroxisome proliferator-activated receptor α (PPARα) nuclear translocation. H2S up-regulates the expression of ABCA1 by promoting the nuclear translocation of PPARα, providing a fundamental mechanism for the anti-atherogenic activity of H2S. H2S may be a promising potential drug candidate for the treatment of atherosclerosis. PMID:27136542

  20. Comparison of MALDI-TOF MS, nucleic acid hybridization and the MPT64 immunochromatographic test for the identification of M. tuberculosis and non-tuberculosis Mycobacterium species.

    PubMed

    Şamlı, Asuman; İlki, Arzu

    2016-10-01

    Mycobacteria are an important cause of morbidity in humans. Rapid and accurate mycobacterial identification is important for improving patient outcomes. However, identification of Mycobacterium species is not easy, due to the slow and fastidious growth of mycobacteria. Recently, biochemical, sequencing, and probing methods have come to be used for identification. This study compared the performance of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) for the identification of M.tuberculosis and non-tuberculosis Mycobacteria (NTM) to those of nucleic acid hybridization (NAH) and the MPT64 immunochromatographic test. A total of 69 isolates from Marmara University Hospital, Microbiology Laboratory obtained between 2012 and 2013 were included in our study. All strains were grown on Lowenstein-Jensen and Middlebrook 7H9 medium. Among the 69 isolates, 56 (81%) were isolated as Mycobacterium tuberculosis complex (MTC), and 13 (19%) were isolated as NTM by the MPT64 ICT. NAH was able to identify all isolates to the species level. The isolated NTM included M. intracellulare (n:5), M. lentiflavum (n:3), M. xenopi (n:2), M. malmoense (n:1), M. abscessus (n:1), and M. avium (n:1). MALDI-TOF MS identified 88% of the mycobacterial isolates. All M. tuberculosis strains were identified correctly, but the ratio was 38.5% for NTM. Mycobacterial identification using MALDI-TOF MS takes 45 minutes and costs 3 Euro/test, whereas mycobacterial identification using NAH takes 6-7 hours and costs 30 Euro/test. In conclusion, MALDI-TOF MS has the potential to identify mycobacteria in the clinical laboratory setting by reducing identification turnaround time and laboratory costs for isolate referral.

  1. In vitro germination of zygotic embryos of hybrid BRS Manicoré (E. guineensis X E. oleifera).

    PubMed

    Bonetti, Keila A P; Quoirin, Marguerite; Quisen, Regina C; Lima, Suelen C S

    2016-01-01

    The interspecific oil palm hybrid BRS Manicoré (E. guineensis x E. oleifera) has superior agronomic characteristics. However, the germination rate is low (30%) and the process is slow when the seeds are sown in a conventional form. The purpose of this study was to optimize the in vitro germination of zygotic embryos of this hybrid comparing seed lots. The viability of zygotic embryos was evaluated by the tetrazolium test (0.075%) for 4 h. The embryos were cultured on MS and Y3 culture media, with and without the addition of NaH2PO4, as well as on MS, MS1/2 and N6 medium. In MS medium containing NaH2PO4, the germination rate was increased from 40 to 70% in comparison with the medium without sodium phosphate. The comparison between the culture media MS, MS 1/2, N6 and Y3 showed that 75% of zygotic embryos cultured in the Y3 medium formed whole plants (with roots and shoots defined), a higher percentage than embryos cultured on MS, MS 1/2 and N6 media (46, 35 and 17% respectively). In the same Y3 culture medium, the embryos were larger (36% ≥ 2 cm and 30% ≥ 5 cm) than in the other media. Results obtained by the tetrazolium test were similar to those of germination, showing the effect of the genotype of each seed lot. For the germination and development of plantlets it is essential to add NaH2PO4 to a culture medium containing no phosphate or with a low phosphate concentration.

  2. Sodium hydrosulfide alleviates lung inflammation and cell apoptosis following resuscitated hemorrhagic shock in rats

    PubMed Central

    Xu, Dun-quan; Gao, Cao; Niu, Wen; Li, Yan; Wang, Yan-xia; Gao, Chang-jun; Ding, Qian; Yao, Li-nong; Chai, Wei; Li, Zhi-chao

    2013-01-01

    Aim: To investigate the protective effects of hydrogen sulfide (H2S) against inflammation, oxidative stress and apoptosis in a rat model of resuscitated hemorrhagic shock. Methods: Hemorrhagic shock was induced in adult male SD rats by drawing blood from the femoral artery for 10 min. The mean arterial pressure was maintained at 35–40 mmHg for 1.5 h. After resuscitation the animals were observed for 200 min, and then killed. The lungs were harvested and bronchoalveolar lavage fluid was prepared. The levels of relevant proteins were examined using Western blotting and immunohistochemical analyses. NaHS (28 μmol/kg, ip) was injected before the resuscitation. Results: Resuscitated hemorrhagic shock induced lung inflammatory responses and significantly increased the levels of inflammatory cytokines IL-6, TNF-α, and HMGB1 in bronchoalveolar lavage fluid. Furthermore, resuscitated hemorrhagic shock caused marked oxidative stress in lung tissue as shown by significant increases in the production of reactive oxygen species H2O2 and ·OH, the translocation of Nrf2, an important regulator of antioxidant expression, into nucleus, and the decrease of thioredoxin 1 expression. Moreover, resuscitated hemorrhagic shock markedly increased the expression of death receptor Fas and Fas-ligand and the number apoptotic cells in lung tissue, as well as the expression of pro-apoptotic proteins FADD, active-caspase 3, active-caspase 8, Bax, and decreased the expression of Bcl-2. Injection with NaHS significantly attenuated these pathophysiological abnormalities induced by the resuscitated hemorrhagic shock. Conclusion: NaHS administration protects rat lungs against inflammatory responses induced by resuscitated hemorrhagic shock via suppressing oxidative stress and the Fas/FasL apoptotic signaling pathway. PMID:24122010

  3. Experimental Study of the Effects of EIPA, Losartan, and BQ-123 on Electrophysiological Changes Induced by Myocardial Stretch.

    PubMed

    Chorro, Francisco J; Canto, Irene Del; Brines, Laia; Such-Miquel, Luis; Calvo, Conrado; Soler, Carlos; Zarzoso, Manuel; Trapero, Isabel; Tormos, Álvaro; Such, Luis

    2015-12-01

    Mechanical response to myocardial stretch has been explained by various mechanisms, which include Na(+)/H(+) exchanger activation by autocrine-paracrine system activity. Drug-induced changes were analyzed to investigate the role of these mechanisms in the electrophysiological responses to acute myocardial stretch. Multiple epicardial electrodes and mapping techniques were used to analyze changes in ventricular fibrillation induced by acute myocardial stretch in isolated perfused rabbit hearts. Four series were studied: control (n = 9); during perfusion with the angiotensin receptor blocker losartan (1 μM, n = 8); during perfusion with the endothelin A receptor blocker BQ-123 (0.1 μM, n = 9), and during perfusion with the Na(+)/H(+) exchanger inhibitor EIPA (5-[N-ethyl-N-isopropyl]-amiloride) (1 μM, n = 9). EIPA attenuated the increase in the dominant frequency of stretch-induced fibrillation (control=40.4%; losartan=36% [not significant]; BQ-123=46% [not significant]; and EIPA=22% [P<.001]). During stretch, the activation maps were less complex (P<.0001) and the spectral concentration of the arrhythmia was greater (greater regularity) in the EIPA series: control=18 (3%); EIPA = 26 (9%) (P < .02); losartan=18 (5%) (not significant); and BQ-123=18 (4%) (not significant). The Na(+)/H(+) exchanger inhibitor EIPA attenuated the electrophysiological effects responsible for the acceleration and increased complexity of ventricular fibrillation induced by acute myocardial stretch. The angiotensin II receptor antagonist losartan and the endothelin A receptor blocker BQ-123 did not modify these effects. Copyright © 2014 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

  4. Hydrogen sulfide activates TRPA1 and releases 5-HT from epithelioid cells of the chicken thoracic aorta.

    PubMed

    Delgermurun, Dugar; Yamaguchi, Soichiro; Ichii, Osamu; Kon, Yasuhiro; Ito, Shigeo; Otsuguro, Ken-Ichi

    2016-09-01

    Epithelioid cells in the chicken thoracic aorta are chemoreceptor cells that release 5-HT in response to hypoxia. It is likely that these cells play a role in chemoreception similar to that of glomus cells in the carotid bodies of mammals. Recently, H2S was reported to be a key mediator of carotid glomus cell responses to hypoxia. The aim of the present study was to reveal the mechanism of action of H2S on 5-HT outflow from chemoreceptor cells in the chicken thoracic aorta. The 5-HT outflow induced by NaHS, an H2S donor, and Na2S3, a polysulfide, was measured by using a HPLC equipped with an electrochemical detector. NaHS (0.3-3mM) caused a concentration-dependent increase in 5-HT outflow, which was significantly inhibited by the removal of extracellular Ca(2+). 5-HT outflow induced by NaHS (0.3mM) was also significantly inhibited by voltage-dependent L- and N-type Ca(2+) channel blockers and a selective TRPA1 channel blocker. Cinnamaldehyde, a TRPA1 agonist, mimicked the secretory response to H2S. 5-HT outflow induced by Na2S3 (10μM) was also inhibited by the TRPA1 channel blocker. Furthermore, the expression of TRPA1 was localized to 5-HT-containing chemoreceptor cells in the aortic wall. These findings suggest that the activation of TRPA1 and voltage-dependent Ca(2+) channels is involved in H2S-evoked 5-HT release from chemoreceptor cells in the chicken aorta. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Angiotensin 2 directly increases rabbit renal brush-border membrane sodium transport: Presence of local signal transduction system

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Morduchowicz, G.A.; Sheikh-Hamad, D.; Dwyer, B.E.

    1991-05-01

    In the present study, the authors have examined the direct actions of angiotensin II (AII) in rabbit renal brush border membrane (BBM) where binding sites for AII exist. Addition of AII (10(-11)-10(-7) M) was found to stimulate 22Na+ uptake by the isolated BBM vesicles directly. All did not affect the Na(+)-dependent BBM glucose uptake, and the effect of AII on BBM 22Na+ uptake was inhibited by amiloride, suggesting the involvement of Na+/H+ exchange mechanism. BBM proton permeability as assessed by acridine orange quenching was not affected by AII, indicating the direct effect of AII on Na+/H+ antiport system. In searchmore » of the signal transduction mechanism, it was found that AII activated BBM phospholipase A2 (PLA) and that BBM contains a 42-kDa guanine nucleotide-binding regulatory protein (G-protein) that underwent pertussis toxin (PTX)-catalyzed ADP-ribosylation. Addition of GTP potentiated, while GDP-beta S or PTX abolished, the effects of AII on BBM PLA and 22Na+ uptake, suggesting the involvement of G-protein in AII's actions. On the other hand, inhibition of PLA by mepacrine prevented AII's effect on BBM 22Na+ uptake, and activation of PLA by mellitin or addition of arachidonic acid similarly enhanced BBM 22Na+ uptake, suggesting the role of PLA activation in mediating AII's effect on BBM 22Na+ uptake. In summary, results of the present study show a direct stimulatory effect of AII on BBM Na+/H+ antiport system, and suggest the presence of a local signal transduction system involving G-protein mediated PLA activation.« less

  6. Digitalisierung im Verteilnetz: Evolution oder Revolution anhand konkreter Beispiele

    NASA Astrophysics Data System (ADS)

    Krone, Oliver; Bachmann, Maurus

    Durch die Integration der neuen erneuerbaren Energien steht das Stromnetz vor großen Herausforderungen. Das Energiesystem als Gesamtes und die Verteilnetze im Speziellen werden smart. Anhand konkreter Beispiele wird aufgezeigt, wie die Digitalisierung im Elektrizitätsnetz voranschreitet. Diese Entwicklung ist eine Evolution, nicht aber eine Revolution.

  7. Stein-Schere-Papier

    NASA Astrophysics Data System (ADS)

    Springborn, Boris

    Wie gewinnt man im Spiel? Die Analyse von Strategien bei Gesellschaftsspielen ist ein Thema der mathematischen Spieltheorie. Mit ihren Methoden kann man aber nicht nur Spiele wie Schach oder Skat untersuchen, sondern auch verschiedenste Konfliktsituationen, bei denen das Schicksal jedes einzelnen Akteurs nicht nur vom eigenen Verhalten abhängt, sondern auch vom Verhalten der anderen, die ebenso wie er versuchen, ein für sie selbst möglichst positives Ergebnis herauszuschlagen. Die Spieltheorie hat großen Einfluss in den Wirtschaftswissenschaften. Auch in der Psychologie, Soziologie, Biologie und der Militärwissenschaft findet sie Anwendung. In der folgenden Aufgabe geht es aber tatsächlich um ein Spiel, und zwar um ein sehr einfaches, das jeder kennt. Trotzdem ist die Lösung nicht ganz einfach, und wer sie findet, hat schon die eine oder andere grundlegende Idee der Spieltheorie verstanden.

  8. Milch, Milchprodukte, Analoge und Speiseeis

    NASA Astrophysics Data System (ADS)

    Coors, Ursula

    Die Produktpalette Milch und Erzeugnisse aus Milch beinhaltet Konsummilch, die aus Milch oder Bestandteilen der Milch hergestellten Milcherzeugnisse wie Sauermilch-, Joghurt-, Kefir-, Buttermilch-, Sahne-, Kondensmilch-, Trockenmilch- und Molkenerzeugnisse, Milchmisch- und Molkenmischprodukte (Produkte mit beigegebenen Lebensmitteln), Milchzucker, Milcheiweißerzeugnisse, Milchfette und Käse.

  9. Germany’s Chosen Path: Domestic Security Institutions in the Berlin Republic 1990-97.

    DTIC Science & Technology

    1997-12-01

    wird vom Neorealismusparadigma unterstotzt, hier dargestel It durch Kenneth Waltz. Das liberate Paradigma unterstUtzt die Perspektive der "Kultur von Zur... Paradigma folgen. Urn diesen aktuellen Weg in Richtung Realismus zu andern, mul$ Deutschland bestimmte Institutionen verandern oder abschaffen. In der

  10. Hydrogen sulfide regulates intracellular Ca2+ concentration in endothelial cells from excised rat aorta.

    PubMed

    Moccia, Francesco; Bertoni, Giuseppe; Pla, Alessandra Florio; Dragoni, Silvia; Pupo, Emanuela; Merlino, Annalisa; Mancardi, Daniele; Munaron, Luca; Tanzi, Franco

    2011-09-01

    Hydrogen sulphide (H2S) is a recently discovered gasotransmitter that may regulate a growing number of endothelial functions, including nitric oxide (NO) release, proliferation, adhesion and migration, which are the key steps of angiogenesis. The mechanism whereby H2S impacts on endothelial physiology is still unclear: however, the aforementioned processes are driven by an increase in intracellular Ca2+ concentration ([Ca2+]i). In the present study, we exploited the excised rat aorta to gain insights into the regulation of [Ca2+]i by H2S within in situ endothelial cells (ECs). Sodium hydrosulphide (NaHS), a H2S donor, caused an elevation in [Ca2+]i, which disappeared in absence of extracellular Ca2+. NaHSinduced Ca2+ inflow was sensitive to high doses of Gd3+, but not BTP-2. Inhibition of the reverse-mode of the Na+-Ca2+ exchanger (NCX), with KB-R7943 or upon removal of extracellular Na+, abrogated the Ca2+ response to NaHS. Moreover, NaHS-elicited Ca2+ entry was significantly reduced by TEA and glybenclamide, which hinted at the involvement of ATP-dependent K+ (KATP) channels. Conversely, NaHS-evoked Ca2+ signal was not affected by the reducing agent, dithiothreitol. Acute addition of NaHS hindered both Ca2+ release and Ca2+ entry induced by ATP, a physiological agonist of ECs. Consistently, inhibition of endogenous H2S synthesis with DL-propargylglycine impaired ATP-induced Ca2+ inflow, whereas it did not affect Ca2+ mobilization. These data provide the first evidence that H2S may stimulate Ca2+ influx into ECs by recruiting the reverse-mode of NCX and KATP channels. In addition, they show that such gasotransmitter may modulate the Ca2+ signals elicited by physiological stimuli in intact endothelium.

  11. H₂S protecting against lung injury following limb ischemia-reperfusion by alleviating inflammation and water transport abnormality in rats.

    PubMed

    Qi, Qi Ying Chun; Chen, Wen; Li, Xiao Ling; Wang, Yu Wei; Xie, Xiao Hua

    2014-06-01

    To investigate the effect of H₂S on lower limb ischemia-reperfusion (LIR) induced lung injury and explore the underlying mechanism. Wistar rats were randomly divided into control group, IR group, IR+ Sodium Hydrosulphide (NaHS) group and IR+ DL-propargylglycine (PPG) group. IR group as lung injury model induced by LIR were given 4 h reperfusion following 4 h ischemia of bilateral hindlimbs with rubber bands. NaHS (0.78 mg/kg) as exogenous H₂S donor and PPG (60 mg/kg) which can suppress endogenous H₂S production were administrated before LIR, respectively. The lungs were removed for histologic analysis, the determination of wet-to-dry weight ratios and the measurement of mRNA and protein levels of aquaporin-1 (AQP₁), aquaporin-5 (AQP₅) as indexes of water transport abnormality, and mRNA and protein levels of Toll-like receptor 4 (TLR₄), myeloid differentiation primary-response gene 88 (MyD88) and p-NF-κB as indexes of inflammation. LIR induced lung injury was accompanied with upregulation of TLR₄-Myd88-NF-κB pathway and downregulation of AQP1/AQP₅. NaHS pre-treatment reduced lung injury with increasing AQP₁/AQP₅ expression and inhibition of TLR₄-Myd88-NF-κB pathway, but PPG adjusted AQP₁/AQP₅ and TLR4 pathway to the opposite side and exacerbated lung injury. Endogenous H₂S, TLR₄-Myd88-NF-κB pathway and AQP₁/AQP₅ were involved in LIR induced lung injury. Increased H₂S would alleviate lung injury and the effect is at least partially depend on the adjustment of TLR₄-Myd88-NF-κB pathway and AQP₁/AQP₅ expression to reduce inflammatory reaction and lessen pulmonary edema. Copyright © 2014 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

  12. Clinical Outcomes of Hip Arthroscopy in Patients 60 or Older: A Minimum of 2-Year Follow-up.

    PubMed

    Capogna, Brian M; Ryan, Michael K; Begly, John P; Chenard, Kristofer E; Mahure, Siddharth A; Youm, Thomas

    2016-12-01

    To examine clinical outcomes and survivorship in patients aged 60 years or older who underwent hip arthroscopy for management of hip pain. Prospectively collected data for patients 60 or older undergoing hip arthroscopy were obtained. All patients were indicated for hip arthroscopy based on standard preoperative examination as well as routine and advanced imaging. Demographic data, diagnosis, and details regarding operative procedures were collected. Baseline preoperative modified Harris Hip Scores (mHHS) and Non-arthritic Hip Scores (NAHS) were compared to mHHS and NAHS at the 2-year follow-up. Survivorship was assessed to determine failure rates, with failure defined as any subsequent ipsilateral revision arthroscopic surgery and/or hip arthroplasty. Forty-two patients met inclusion criteria. Mean age (standard deviation) and body mass index were 65.8 years (4.5 years) and 26.1 (4.7), respectively. Baseline mean mHHS and NAHS for all patients improved from 47.8 (±12.5) and 47.3 (±13.6) to 75.6 (±17.6) and 78.3 (±18.6), respectively (P < .001 for both). Five patients (11.9%) met failure criteria and underwent additional surgery at an average of 14.8 (8-30) months. Three underwent conversion to total hip arthroplasty (7.1%), whereas 2 had revision arthroscopy with cam/pincer resection and labral repair for recurrent symptoms (4.7%). One- and 2-year survival rates were 95.2% and 88.9%, respectively. Our results suggest that in patients 60 or older with Tonnis grade 0 or 1 osteoarthritic changes on initial radiographs-treatment with hip arthroscopy can lead to reliable improvement in early outcomes. As use of hip arthroscopy for treatment of mechanical hip pain increases, additional studies with long-term follow-up are needed. Level IV, therapeutic case series. Copyright © 2016 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

  13. Hydrogen sulfide triggers late-phase preconditioning in postischemic small intestine by an NO- and p38 MAPK-dependent mechanism

    PubMed Central

    Yusof, Mozow; Kamada, Kazuhiro; Kalogeris, Theodore; Gaskin, F. Spencer; Korthuis, Ronald J.

    2009-01-01

    Hydrogen sulfide (H2S) is one of three endogenous gases, along with carbon monoxide (CO) and nitric oxide (NO), that exert a variety of important vascular actions in vivo. Although it has been demonstrated that CO or NO can trigger the development of a preconditioned phenotype in postischemic tissues, it is unclear whether H2S may also induce protection in organs subsequently exposed to ischemia-reperfusion (I/R). In light of these observations, we postulated that preconditioning with the exogenous H2S donor sodium hydrosulfide (NaHS-PC) would inhibit leukocyte rolling (LR) and adhesion (LA) induced by I/R. We used intravital microscopic techniques to demonstrate that NaHS-PC 24 h, but not 1 h, before I/R causes postcapillary venules to shift to an anti-inflammatory phenotype in wild-type (WT) mice such that these vessels fail to support LR and LA during reperfusion. The protective effect of NaHS-PC on LR was largely abolished by coincident pharmacological inhibition of NO synthase (NOS) in WT animals and was absent in endothelial NOS-deficient (eNOS−/−) mice. A similar pattern of response was noted in WT mice treated concomitantly with NaHS plus p38 mitogen-activated protein kinase (MAPK) inhibitors (SB 203580 or SK-86002). Whereas the reduction in LA induced by antecedent NaHS was attenuated by pharmacological inhibition of NOS or p38 MAPK in WT mice, the antiadhesive effect of NaHS was still evident in eNOS−/− mice. Thus NaHS-PC prevents LR and LA by triggering the activation of an eNOS- and p38 MAPK-dependent mechanism. However, the role of eNOS in the antiadhesive effect of NaHS-PC was less prominent than its effect to reduce LR. PMID:19168723

  14. Evidence for the role of a Na(+)/HCO(3)(-) cotransporter in trout hepatocyte pHi regulation.

    PubMed

    Furimsky, M; Moon, T W; Perry, S F

    2000-07-01

    The mechanisms of intracellular pH (pHi) regulation were examined in hepatocytes of the rainbow trout Oncorhynchus mykiss. pHi was monitored using the pH-sensitive fluorescent dye BCECF, and the effects of various media and pharmacological agents were examined for their influence on baseline pHi and recovery rates from acid and base loading. Rates of Na(+) uptake were measured using (22)Na, and changes in membrane potential were examined using the potentiometric fluorescent dye Oxonol VI. The rate of proton extrusion following acid loading was diminished by the blockade of either Na(+)/H(+) exchange (using amiloride) or anion transport (using DIDS). The removal of external HCO(3)(-) and the abolition of outward K(+) diffusion by the channel blocker Ba(2+) also decreased the rate of proton extrusion following acid load. Depolarization of the cell membrane with 50 mmol l(-)(1) K(+), however, did not affect pHi. The rate of recovery from base loading was significantly diminished by the blockade of anion transport, removal of external HCO(3)(-) and, to a lesser extent, by blocking Na(+)/H(+) exchange. The blockade of K(+) conductance had no effect. The decrease in Na(+) uptake rate observed in the presence of the anion transport blocker DIDS and the DIDS-sensitive hyperpolarization of membrane potential during recovery from acid loading suggest that a Na(+)-dependent electrogenic transport system is involved in the restoration of pHi after intracellular acidification. The effects on baseline pHi indicate that the different membrane exchangers are tonically active in the maintenance of steady-state pHi. This study confirms the roles of a Na(+)/H(+) exchanger and a Cl(-)/HCO(3)(-) exchanger in the regulation of trout hepatocyte pHi and provides new evidence that a Na(+)/HCO(3)(-) cotransporter contributes to pHi regulation.

  15. Inhibition of RhoA/Rho kinase pathway and smooth muscle contraction by hydrogen sulfide.

    PubMed

    Nalli, Ancy D; Wang, Hongxia; Bhattacharya, Sayak; Blakeney, Bryan A; Murthy, Karnam S

    2017-10-01

    Hydrogen sulfide (H 2 S) plays an important role in smooth muscle relaxation. Here, we investigated the expression of enzymes in H 2 S synthesis and the mechanism regulating colonic smooth muscle function by H 2 S. Expression of cystathionine-γ-lyase (CSE), but not cystathionine-β-synthase (CBS), was identified in the colonic smooth muscle of rabbit, mouse, and human. Carbachol (CCh)-induced contraction in rabbit muscle strips and isolated muscle cells was inhibited by l-cysteine (substrate of CSE) and NaHS (an exogenous H 2 S donor) in a concentration-dependent fashion. H 2 S induced S-sulfhydration of RhoA that was associated with inhibition of RhoA activity. CCh-induced Rho kinase activity also was inhibited by l-cysteine and NaHS in a concentration-dependent fashion. Inhibition of CCh-induced contraction by l-cysteine was blocked by the CSE inhibitor, dl-propargylglycine (DL-PPG) in dispersed muscle cells. Inhibition of CCh-induced Rho kinase activity by l-cysteine was blocked by CSE siRNA in cultured cells and DL-PPG in dispersed muscle cells. Stimulation of Rho kinase activity and muscle contraction in response to CCh was also inhibited by l-cysteine or NaHS in colonic muscle cells from mouse and human. Collectively, our studies identified the expression of CSE in colonic smooth muscle and determined that sulfhydration of RhoA by H 2 S leads to inhibition of RhoA and Rho kinase activities and muscle contraction. The mechanism identified may provide novel therapeutic approaches to mitigate gastrointestinal motility disorders. © 2017 The Authors. Pharmacology Research & Perspectives published by John Wiley & Sons Ltd, British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics.

  16. Hydrogen sulphide facilitates exocytosis by regulating the handling of intracellular calcium by chromaffin cells.

    PubMed

    de Pascual, Ricardo; Baraibar, Andrés M; Méndez-López, Iago; Pérez-Ciria, Martín; Polo-Vaquero, Ignacio; Gandía, Luis; Ohia, Sunny E; García, Antonio G; de Diego, Antonio M G

    2018-05-02

    Gasotransmitter hydrogen sulphide (H 2 S) has emerged as a regulator of multiple physiological and pathophysiological processes throughout. Here, we have investigated the effects of NaHS (fast donor of H 2 S) and GYY4137 (GYY, slow donor of H 2 S) on the exocytotic release of catecholamines from fast-perifused bovine adrenal chromaffin cells (BCCs) challenged with sequential intermittent pulses of a K + -depolarizing solution. Both donors caused a concentration-dependent facilitation of secretion. This was not due to an augmentation of Ca 2+ entry through voltage-activated Ca 2+ channels (VACCs) because, in fact, NaHS and GYY caused a mild inhibition of whole-cell Ca 2+ currents. Rather, the facilitation of exocytosis seemed to be associated to an augmented basal [Ca 2+ ] c and the K + -elicited [Ca 2+ ] c transients; such effects of H 2 S donors are aborted by cyclopiazonic acid (CPA), that causes endoplasmic reticulum (ER) Ca 2+ depletion through sarcoendoplasmic reticulum Ca2+ ATPase inhibition and by protonophore carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone (FCCP), that impedes the ability of mitochondria to sequester cytosolic Ca 2+ during cell depolarization. Inasmuch as CPA and FCCP reversed the facilitation of secretion triggered by K + in the presence of NaHS and GYY, is seems that such facilitation is tightly coupled to Ca 2+ handling by the ER and mitochondria. On the basis of these results, we propose that H 2 S regulates catecholamine secretory responses triggered by K + in BCCs by (i) mobilisation of ER Ca 2+ and (ii) interference with mitochondrial Ca 2+ circulation. In so doing, the clearance of the [Ca 2+ ] c transient will be delayed and the Ca 2+ -dependent trafficking of secretory vesicles will be enhanced to overfill the secretory machinery with new vesicles to enhance exocytosis.

  17. Acid extrusion via blood–brain barrier causes brain alkalosis and seizures after neonatal asphyxia

    PubMed Central

    Helmy, Mohamed M.; Ruusuvuori, Eva; Watkins, Paul V.; Voipio, Juha; Kanold, Patrick O.; Kaila, Kai

    2012-01-01

    Birth asphyxia is often associated with a high seizure burden that is predictive of poor neurodevelopmental outcome. The mechanisms underlying birth asphyxia seizures are unknown. Using an animal model of birth asphyxia based on 6-day-old rat pups, we have recently shown that the seizure burden is linked to an increase in brain extracellular pH that consists of the recovery from the asphyxia-induced acidosis, and of a subsequent plateau level well above normal extracellular pH. In the present study, two-photon imaging of intracellular pH in neocortical neurons in vivo showed that pH changes also underwent a biphasic acid–alkaline response, resulting in an alkaline plateau level. The mean alkaline overshoot was strongly suppressed by a graded restoration of normocapnia after asphyxia. The parallel post-asphyxia increase in extra- and intracellular pH levels indicated a net loss of acid equivalents from brain tissue that was not attributable to a disruption of the blood–brain barrier, as demonstrated by a lack of increased sodium fluorescein extravasation into the brain, and by the electrophysiological characteristics of the blood–brain barrier. Indeed, electrode recordings of pH in the brain and trunk demonstrated a net efflux of acid equivalents from the brain across the blood–brain barrier, which was abolished by the Na/H exchange inhibitor, N-methyl-isobutyl amiloride. Pharmacological inhibition of Na/H exchange also suppressed the seizure activity associated with the brain-specific alkalosis. Our findings show that the post-asphyxia seizures are attributable to an enhanced Na/H exchange-dependent net extrusion of acid equivalents across the blood–brain barrier and to consequent brain alkalosis. These results suggest targeting of blood–brain barrier-mediated pH regulation as a novel approach in the prevention and therapy of neonatal seizures. PMID:23125183

  18. Intracellular pH changes in human aortic smooth muscle cells in response to fluid shear stress

    NASA Technical Reports Server (NTRS)

    Stamatas, G. N.; Patrick, C. W. Jr; McIntire, L. V.

    1997-01-01

    The smooth muscle cell (SMC) layers of human arteries may be exposed to blood flow after endothelium denudation, for example, following balloon angioplasty treatment. These SMCs are also constantly subjected to pressure driven transmural fluid flow. Flow-induced shear stress can alter SMC growth and metabolism. Signal transduction mechanisms involved in these flow effects on SMCs are still poorly understood. In this work, the hypothesis that shear stress alters the intracellular pH (pHi) of SMC is examined. When exposed to venous and arterial levels of shear stress, human aortic smooth muscle cells (hASMC) undergo alkalinization. The alkalinization plateau persisted even after 20 min of cell exposure to flow. Addition of amiloride (10 micromoles) or its 5-(N-ethyl-N-isopropyl) analog (EIPA, 10 micromoles), both Na+/H+ exchanger inhibitors, attenuated intracellular alkalinization, suggesting the involvement of the Na+/H+ exchanger in this response. The same concentrations of these inhibitors did not show an effect on pHi of hASMCs in static culture. 4-Acetamido-4'-isothio-cyanatostilbene-2,2'-disulfonic acid (SITS, 1 mM), a Cl-/HCO3- exchange inhibitor, affected the pHi of hASMCs both in static and flow conditions. Our results suggest that flow may perturb the Na+/H+ exchanger leading to an alkalinization of hASMCs, a different response from the flow-induced acidification seen with endothelial cells at the same levels of shear stress. Understanding the flow-induced signal transduction pathways in the vascular cells is of great importance in the tissue engineering of vascular grafts. In the case of SMCs, the involvement of pHi changes in nitric oxide production and proliferation regulation highlights further the significance of such studies.

  19. The metabolic response in fish to mildly elevated water temperature relates to species-dependent muscular concentrations of imidazole compounds and free amino acids.

    PubMed

    Geda, Fikremariam; Declercq, Annelies M; Remø, Sofie C; Waagbø, Rune; Lourenço, Marta; Janssens, Geert P J

    2017-04-01

    Fish species show distinct differences in their muscular concentrations of imidazoles and free amino acids (FAA). This study was conducted to investigate whether metabolic response to mildly elevated water temperature (MEWT) relates to species-dependent muscular concentrations of imidazoles and FAA. Thirteen carp and 17 Nile tilapia, housed one per aquarium, were randomly assigned to either acclimation (25°C) or MEWT (30°C) for 14 days. Main muscular concentrations were histidine (HIS; P<0.001) in carp versus N-α-acetylhistidine (NAH; P<0.001) and taurine (TAU; P=0.001) in tilapia. Although the sum of imidazole (HIS+NAH) and TAU in muscle remained constant over species and temperatures (P>0.05), (NAH+HIS)/TAU ratio was markedly higher in carp versus tilapia, and decreased with MEWT only in carp (P<0.05). Many of the muscular FAA concentrations were higher in carp than in tilapia (P<0.05). Plasma acylcarnitine profile suggested a higher use of AA and fatty acids in carp metabolism (P<0.05). On the contrary, the concentration of 3-hydroxyisovalerylcarnitine, a sink of leucine catabolism, (P=0.009) pointed to avoidance of leucine use in tilapia metabolism. Despite a further increase of plasma longer-chain acylcarnitines in tilapia at MEWT (P=0.009), their corresponding beta-oxidation products (3-hydroxy-longer-chain acylcarnitines) remained constant. Together with higher plasma non-esterified fatty acids (NEFA) in carp (P=0.001), the latter shows that carp, being a fatter fish, more readily mobilises fat than tilapia at MEWT, which coincides with more intensive muscular mobilization of imidazoles. This study demonstrates that fish species differ in their metabolic response to MEWT, which is associated with species-dependent changes in muscle imidazole to taurine ratio. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. FOLDING OF DIPHTHERIA TOXIN T-DOMAIN IN THE PRESENCE OF AMPHIPOLS AND FLUORINATED SURFACTANTS: TOWARD THERMODYNAMIC MEASUREMENTS OF MEMBRANE PROTEIN FOLDING

    PubMed Central

    Kyrychenko, Alexander; Rodnin, Mykola V.; Vargas-Uribe, Mauricio; Sharma, Shivaji K.; Durand, Grégory; Pucci, Bernard; Popot, Jean-Luc; Ladokhin, Alexey S.

    2011-01-01

    Solubilizing membrane proteins for functional, structural and thermodynamic studies is usually achieved with the help of detergents, which tend to destabilize them, however. Several classes of non-detergent surfactants have been designed as milder substitutes for detergents, most prominently amphipathic polymers called 'amphipols' and fluorinated surfactants. Here we test the potential usefulness of these compounds for thermodynamic studies by examining their effect on conformational transitions of the diphtheria toxin T-domain. The advantage of the T-domain as a model system is that it exists as a soluble globular protein at neutral pH yet is converted into a membrane-competent form by acidification and inserts into the lipid bilayer as part of its physiological action. We have examined the effects of various surfactants on two conformational transitions of the T-domain, thermal unfolding and pH-induced transition to a membrane-competent form. All tested detergent and non-detergent surfactants lowered the cooperativity of the thermal unfolding of the T-domain. The dependence of enthalpy of unfolding on surfactant concentration was found to be least for fluorinated surfactants, thus making them useful candidates for thermodynamic studies. Circular dichroism measurements demonstrate that non-ionic homo-polymeric amphipols (NAhPols), unlike any other surfactants, can actively cause a conformational change of the T-domain. NAhPol-induced structural rearrangements are different from those observed during thermal denaturation and are suggested to be related to the formation of the membrane-competent form of the T-domain. Measurements of vesicle content leakage indicate that interaction with NAhPols not only does not prevent the T-domain from inserting into the bilayer, but it can make bilayer permeabilization even more efficient, whereas the pH-dependence of membrane permeabilization becomes more cooperative. PMID:21945883

  1. Comparison of adhesive properties of water- and phosphate-buffer-washed cottonseed meals with cottonseed protein isolate on maple and poplar veneers

    USDA-ARS?s Scientific Manuscript database

    Water- and phosphate buffer (35 mM Na2HPO4/NaH2PO4, pH 7.5)-washed cottonseed meals (abbreviated as WCM and BCM, respectively) could be low-cost and environmentally friendly protein-based adhesives as their preparation does not involve corrosive alkali and acid solutions that are needed for cottonse...

  2. Clifford G. Shull, Neutron Diffraction, Hydrogen Atoms, and Neutron

    Science.gov Websites

    Analysis of NaH and NaD, DOE Technical Report, April 1947 The Diffraction of Neutrons by Crystalline Powders; DOE Technical Report; 1948 Neutron Diffraction Studies, DOE Technical Report, 1948 Laue Structure of Thorium and Zirconium Dihydrides by X-ray and Neutron Diffraction, DOE Technical Report, April

  3. Properties of Fluorinated Graphene Films

    DTIC Science & Technology

    2010-04-01

    Properties of Fluorinated Graphene Films Jeremy T. Robinson,* James S. Burgess, Chad E. Junkermeier, Stefan C. Badescu, Thomas L. Reinecke, F. Keith...G. S.; Graham, A. P.; Kreupl, F.; Seidel , R.; Hoenlein, W. Chem. Phys. Lett. 2004, 399 (1-3), 280– 283. (19) Li, X.; Cai, W.; An, J.; Kim, S.; Nah, J

  4. Azelainsäure 20 % Creme: Auswirkung auf Lebensqualität und Krankheitsaktivität bei erwachsenen Patientinnen mit Acne vulgaris.

    PubMed

    Kainz, Julius Thomas; Berghammer, Gabriele; Auer-Grumbach, Piet; Lackner, Verena; Perl-Convalexius, Sylvia; Popa, Rodica; Wolfesberger, Barbara

    2016-12-01

    Zur Wirksamkeit von Aknetherapien und deren Auswirkungen auf die Lebensqualität erwachsener Patienten liegen kaum Daten vor. ZIEL: Erhebung der Wirkung von Azelainsäure 20 % Creme (Skinoren ® ) auf Akne-Schweregrad und krankheitsbedingte Lebensqualität. Nichtinterventionelle Studie bei erwachsenen Patientinnen mit leichter bis mittelschwerer Akne. Wirksamkeitsparameter waren DLQI sowie Akne-Schweregrad im Gesicht, am Dekolleté sowie am Rücken im Gesamturteil des Prüfarztes (IGA-Skala: Grad 1 = annähernd reine Haut; 2 = leichte Akne; 3 = mittelschwere Akne). Visiten waren zu Studienbeginn sowie nach 4-8 und zwölf Wochen geplant. Von den 251 eingeschlossenen Patientinnen lag zu Studienbeginn bei 59 %, 31 % bzw. 10 % ein IGA-Grad von 1, 2 bzw. 3 vor; die am häufigsten betroffene Hautpartie war das Gesicht (IGA-Grad 2 oder 3: 79 %). Nach zwölf Behandlungswochen war eine signifikante Besserung der Acne vulgaris im Gesicht (IGA-Grad 0 oder 1: 82 %) sowie auf Dekolleté und Rücken feststellbar. Der mediane DLQI-Wert sank von neun zu Studienbeginn auf fünf nach zwölf Behandlungswochen. Neunzig Prozent der behandelnden Ärzte und Patientinnen beurteilten die Verträglichkeit der Behandlung als sehr gut oder gut. Die Anwendung von 20%iger Azelainsäure-Creme führt bei erwachsenen Frauen zu einer signifikanten Besserung der Acne vulgaris und der krankheitsbedingten Lebensqualität. © 2016 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

  5. "Structure-making" ability of Na+ in dilute aqueous solution: an ONIOM-XS MD simulation study.

    PubMed

    Sripa, Pattrawan; Tongraar, Anan; Kerdcharoen, Teerakiat

    2013-02-28

    An ONIOM-XS MD simulation has been performed to characterize the "structure-making" ability of Na(+) in dilute aqueous solution. The region of most interest, i.e., a sphere that includes Na(+) and its surrounding water molecules, was treated at the HF level of accuracy using LANL2DZ and DZP basis sets for the ion and waters, respectively, whereas the rest of the system was described by classical pair potentials. Detailed analyzes of the ONIOM-XS MD trajectories clearly show that Na(+) is able to order the structure of waters in its surroundings, forming two prevalent Na(+)(H(2)O)(5) and Na(+)(H(2)O)(6) species. Interestingly, it is observed that these 5-fold and 6-fold coordinated complexes can convert back and forth with some degrees of flexibility, leading to frequent rearrangements of the Na(+) hydrates as well as numerous attempts of inner-shell water molecules to interchange with waters in the outer region. Such a phenomenon clearly demonstrates the weak "structure-making" ability of Na(+) in aqueous solution.

  6. Petroleum pollution in surface sediments of Daya Bay, South China, revealed by chemical fingerprinting of aliphatic and alicyclic hydrocarbons

    NASA Astrophysics Data System (ADS)

    Gao, Xuelu; Chen, Shaoyong

    2008-10-01

    Nine surface sediments collected from Daya Bay have been Soxhlet-extracted with 2:1 (v/v) dichloromethane-methanol. The non-aromatic hydrocarbon (NAH) fraction of solvent extractable organic matter (EOM) and some bulk geochemical parameters have been analyzed to determine petroleum pollution of the bay. The NAH content varies from 32 to 276 μg g -1 (average 104 μg g -1) dry sediment and accounts for 5.8-64.1% (average 41.6%) of the EOM. n-Alkanes with carbon number ranging from 15 to 35 are identified to be derived from both biogenic and petrogenic sources in varying proportions. The contribution of marine authigenic input to the sedimentary n-alkanes is lower than the allochthonous input based on the average n-C 31/ n-C 19 alkane ratio. 25.6-46.5% of the n-alkanes, with a mean of 35.6%, are contributed by vascular plant wax. Results of unresolved complex mixture, isoprenoid hydrocarbons, hopanes and steranes also suggest possible petroleum contamination. There is strong evidence of a common petroleum contamination source in the bay.

  7. Safer one-pot synthesis of the ‘SHAPE’ reagent 1-methyl-7-nitroisatoic anhydride (1m7)

    PubMed Central

    Turner, Rushia; Shefer, Kinneret; Ares, Manuel

    2013-01-01

    Estimating the reactivity of 2′-hydroxyl groups along an RNA chain of interest aids in the modeling of the folded RNA structure; flexible loops tend to be reactive, whereas duplex regions are generally not. Among the most useful reagents for probing 2′-hydroxyl reactivity is 1-methyl-7-nitroisatoic anhydride (1m7), but the absence of a reliable, inexpensive source has prevented widespread adoption. An existing protocol for the conversion of an inexpensive precursor 4-nitroisatoic anhydride (4NIA) recommends the use of NaH in dimethylformamide (DMF), a reagent combination that most molecular biology labs are not equipped to handle, and that does not scale safely in any case. Here we describe a safer, one-pot method for bulk conversion of 4NIA to 1m7 that reduces costs and bypasses the use of NaH. We show that 1m7 produced by this method is free of side products and can be used to probe RNA structure in vitro. PMID:24141619

  8. Hydrocarbon pollution in the sediment from the Jarzouna-Bizerte coastal area of Tunisia (Mediterranean Sea).

    PubMed

    Zrafi-Nouira, I; Khedir-Ghenim, Z; Zrafi, F; Bahri, R; Cheraeif, I; Rouabhia, M; Saidane-Mosbahi, D

    2008-06-01

    This study investigated the presence and origin of hydrocarbon pollution in industrial waste water sediments found near the Jarzouna (Bizerte, Tunisia) oil refinery. Analyses of surface sediments (layer 1) and deep sediments (layer 2) showed that Total Hydrocarbon (TH) concentrations ranged from 602 +/- 7.638 microg/g in layer-1 to 1270 +/- 2.176 microg/g in layer-2. The results suggest that the deeper the sediment, the higher the level of total hydrocarbon found. The sedimentary Non Aromatic Hydrocarbon (NAH) and Aromatic Hydrocarbon (AH) concentrations ranged from 66.22 +/- 1.516 to 211.82 +/- 10.670 microg/g for NAH, and from 13.84 +/- 0.180 to 115.60 +/- 2.479 microg/g for AH. The high variability of these concentrations was associated with the location of the sediment collection sites. Aliphatic biomarker analysis revealed petroleum contamination close to the refinery rejection site, and biogenic sources further away. Petroleum contamination may be associated with increased industrial activity in the area of Jarzouna-Bizerte in the Mediterranean Sea.

  9. Mechanisms of Sodium Transport in Plants—Progresses and Challenges

    PubMed Central

    Keisham, Monika; Mukherjee, Soumya; Bhatla, Satish C.

    2018-01-01

    Understanding the mechanisms of sodium (Na+) influx, effective compartmentalization, and efflux in higher plants is crucial to manipulate Na+ accumulation and assure the maintenance of low Na+ concentration in the cytosol and, hence, plant tolerance to salt stress. Na+ influx across the plasma membrane in the roots occur mainly via nonselective cation channels (NSCCs). Na+ is compartmentalized into vacuoles by Na+/H+ exchangers (NHXs). Na+ efflux from the plant roots is mediated by the activity of Na+/H+ antiporters catalyzed by the salt overly sensitive 1 (SOS1) protein. In animals, ouabain (OU)-sensitive Na+, K+-ATPase (a P-type ATPase) mediates sodium efflux. The evolution of P-type ATPases in higher plants does not exclude the possibility of sodium efflux mechanisms similar to the Na+, K+-ATPase-dependent mechanisms characteristic of animal cells. Using novel fluorescence imaging and spectrofluorometric methodologies, an OU-sensitive sodium efflux system has recently been reported to be physiologically active in roots. This review summarizes and analyzes the current knowledge on Na+ influx, compartmentalization, and efflux in higher plants in response to salt stress. PMID:29495332

  10. Arbeitsgestaltung und Mitarbeiterqualifizierung

    NASA Astrophysics Data System (ADS)

    Weiss-Oberdorfer, Werner; Hörner, Barbara; Holm, Ruth; Pirner, Evelin

    Die Wertkette gliedert ein Unternehmen in strategisch relevante Tätigkeiten, um dadurch Kostenverhalten sowie vorhandene und potenzielle Differenzierungsquellen zu verstehen. Wenn ein Unternehmen diese strategisch wichtigen Aktivitäten billiger oder besser als seine Konkurrenten erledigt, verschafft es sich einen Wettbewerbsvorteil." Michael Porter, 1985

  11. [Gastro-Oesophageal Reflux Disease - How to Manage if PPI are not Sufficiently Effective, not Tolerated, or not Wished?

    PubMed

    Labenz, Joachim; Koop, Herbert

    2018-03-01

    Die Standardtherapie der GERD mit PPI ist weniger wirksam als gedacht: Mindestens 30 % der Patienten haben persistierende Symptome und Läsionen (Therapielücke). Bei persistierender Symptomatik oder Wunsch einer alternativen Behandlung ist eine stratifizierte Diagnostik erforderlich. Alginate und neue Operationsverfahren erweitern die Therapieoptionen.

  12. Acoustic building infiltration measurement system

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Muehleisen, Ralph T.; Raman, Ganesh

    Systems and methods of detecting and identifying a leak from a container or building. Acoustic pressure and velocity are measured. Acoustic properties are acquired from the measured values. The acoustic properties are converted to infiltration/leakage information. Nearfield Acoustic Holography (NAH) may be one method to detect the leakages from a container by locating the noise sources.

  13. 21 CFR 184.1764 - Sodium hypophosphite.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Sodium hypophosphite. 184.1764 Section 184.1764 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DIRECT... GRAS § 184.1764 Sodium hypophosphite. (a) Sodium hypophosphite (NaH2PO2, CAS Reg. No. 7681-53-0) is a...

  14. Sticktechnologie für medizinische Textilien und Tissue Engineering

    NASA Astrophysics Data System (ADS)

    Karamuk, Erdal; Mayer, Jörg; Wintermantel, Erich

    Textile Strukturen werden in grossem Ausmass als medizinische Implantate eingesetzt, um Weich- und Hartgewebe zu unterstützen oder zu ersetzen. Im Tissue Engineering gewinnen sie an Bedeutung als scaffolds, um biologische Gewebe in vitro zu züchten für anschliessende Implantation oder extrakorporale Anwendungen. Textilien sind gewöhnlich anisotrope zweidimensionale Strukturen mit hoher Steifigkeit in der Ebene und geringer Biegesteifigkeit. Durch eine Vielzahl textiler Prozesse und durch entsprechende Wahl des Fasermaterials ist es möglich, Oberfläche, Porosität und mechanische Anisotropie in hohem Masse zu variieren. Wegen ihrer einzigartigen strukturellen und mechanischen Eigenschaften können faserbasierte Materialien in weitem Masse biologischem Gewebe nachgeahmt werden [1]. Gesticke erweitern das Feld von technischen und besonders medizinischen Textilien, denn sie vereinen sehr hohe strukturelle Variabilität mit der Möglichkeit, mechanische Eigenschaften in einem grossen Bereich einzustellen, um so die mechanischen Anforderungen des Empfängergewebes zu erfüllen (Abb. 42.1).

  15. Spritzgießen

    NASA Astrophysics Data System (ADS)

    Bürkle, Erwin; Ammer, Daniel; Würtele, Martin

    Kunststoffe zu spritzgießen ist eine der fortschrittlichsten Verarbeitungstechnologien. Durch Spritzgießen, ein Verfahren der Urformtechnik werden Formteile in der Regel mit komplexer Geometrie vollautomatisch hergestellt. Ausgehend vom Verfahrensablauf werden Thermoplaste, Duroplaste oder Kautschuk in einer Spritzgießmaschine aus dem Feststoffzustand heraus aufgeschmolzen, in einen formgebenden Hohlraum (Werkzeug) eingespritzt, dort verdichtet, abgekühlt oder zur Reaktion gebracht und dann als Formteil aus dem Werkzeug ausgeworfen. Etwa 60 % aller Kunststoffverarbeitungsmaschinen sind Spritzgießmaschinen (Abb. 26.1). Auf ihnen werden Formteile mit sehr niedrigen Massen im mg-Bereich bis hin zu großen Massen in zwei - z. T. sogar auch dreistelligen kg-Bereich hergestellt. Der Prozess des Spritzgießens nutzt in idealer Weise das besondere physikalische Verhalten der Kunststoffe. In einem verhältnismäßig einfachen Prozess werden durch Erwärmen des Kunststoffes und der nachfolgenden Formgebung im Schmelzezustand mit abschließender Abkühlung in einem formgebenden Werkzeug direkt gebrauchsfertige Formteile hergestellt [1, 31].

  16. Normung (Standardisierung)

    NASA Astrophysics Data System (ADS)

    Kostmann, Dirk

    Normung ist aus dem täglichen Leben nicht wegzudenken. In allen Bereichen des Lebens begegnet man Normen, die Aktivitäten reichen von Festlegungen für Kindersitze im Auto über Implantate zum Gelenkersatz bis zu Schraubengrößen oder Verfahren zur Optimierung von Unternehmen.

  17. Project CHECO Southeast Asia Report. Rules of Engagement - 1 January 1966 - 1 November 1969

    DTIC Science & Technology

    1969-08-31

    O.owngrading of Project CIIECO Report TO: AAC ADC AFAFC AFLC ( Historian ) AFRES AFSC ATC All t-IAC PACAF SAC TAC USA FE USAFSS...k. , ~. t ~ s ipso [aoto a moto ¥>ab?.~ road or· naH. Sc.. an!:fpt-:.~.-.:r,: th:..tt !fOU find a veh-;.cle~ d .;·( .~a’l a5JIOI~ th:u 1..t ~-;f

  18. Workshop on Dextrous Robot Hands: IEEE International Conference on Robotics and Automation. Held in Philadelphia, PA April 25-29, 1988

    DTIC Science & Technology

    1988-04-05

    water in oder to drink from it you will probably reach for it from the side with the forearm midway between pronatio and supinatios (so that the palm...nornal subjects by Wing, Turton & Fraser (1986). Of interest were the elects of the availabilit visial information about reaching on grasp aperture. It

  19. "In Mathe war ich immer schlecht"

    NASA Astrophysics Data System (ADS)

    Beutelspacher, Albrecht

    Genauso wie bei vielen anderen Er scheinungsformen des Lebens (Philosophie, Musik, Liebe) kann Mathematik nicht eindeutig definiert werden. Jede Definition wäre entweder nichtssagend oder zu einengend. Man kann aber versuchen, Mathematik von verschiedenen Seiten zu beleuchten. Dabei offenbaren sich überraschende und tiefe Einblicke in das Wesen der Mathematik.

  20. Analyzing panel acoustic contributions toward the sound field inside the passenger compartment of a full-size automobile.

    PubMed

    Wu, Sean F; Moondra, Manmohan; Beniwal, Ravi

    2015-04-01

    The Helmholtz equation least squares (HELS)-based nearfield acoustical holography (NAH) is utilized to analyze panel acoustic contributions toward the acoustic field inside the interior region of an automobile. Specifically, the acoustic power flows from individual panels are reconstructed, and relative contributions to sound pressure level and spectrum at any point of interest are calculated. Results demonstrate that by correlating the acoustic power flows from individual panels to the field acoustic pressure, one can correctly locate the panel allowing the most acoustic energy transmission into the vehicle interior. The panel on which the surface acoustic pressure amplitude is the highest should not be used as indicative of the panel responsible for the sound field in the vehicle passenger compartment. Another significant advantage of this HELS-based NAH is that measurements of the input data only need to be taken once by using a conformal array of microphones in the near field, and ranking of panel acoustic contributions to any field point can be readily performed. The transfer functions between individual panels of any vibrating structure to the acoustic pressure anywhere in space are calculated not measured, thus significantly reducing the time and effort involved in panel acoustic contributions analyses.

  1. Constitutive Expression of Mammalian Nitric Oxide Synthase in Tobacco Plants Triggers Disease Resistance to Pathogens

    PubMed Central

    Chun, Hyun Jin; Park, Hyeong Cheol; Koo, Sung Cheol; Lee, Ju Huck; Park, Chan Young; Choi, Man Soo; Kang, Chang Ho; Baek, Dongwon; Cheong, Yong Hwa; Yun, Dae-Jin; Chung, Woo Sik; Cho, Moo Je; Kim, Min Chul

    2012-01-01

    Nitric oxide (NO) is known for its role in the activation of plant defense responses. To examine the involvement and mode of action of NO in plant defense responses, we introduced calmodulin-dependent mammalian neuronal nitric oxide synthase (nNOS), which controls the CaMV35S promoter, into wild-type and NahG tobacco plants. Constitutive expression of nNOS led to NO production and triggered spontaneous induction of leaf lesions. Transgenic plants accumulated high amounts of H2O2, with catalase activity lower than that in the wild type. nNOS transgenic plants contained high levels of salicylic acid (SA), and they induced an array of SA-, jasmonic acid (JA)-, and/or ethylene (ET)-related genes. Consequently, NahG co-expression blocked the induction of systemic acquired resistance (SAR)-associated genes in transgenic plants, implying SA is involved in NO-mediated induction of SAR genes. The transgenic plants exhibited enhanced resistance to a spectrum of pathogens, including bacteria, fungi, and viruses. Our results suggest a highly ranked regulatory role for NO in SA-, JA-, and/or ET-dependent pathways that lead to disease resistance. PMID:23124383

  2. Determination of hydrolyzable tannins in the fruit of Terminalia chebula Retz. by high-performance liquid chromatography and capillary electrophoresis.

    PubMed

    Juang, Lih-Jeng; Sheu, Shuenn-Jyi; Lin, Ta-Chen

    2004-06-01

    A RP-HPLC method for determining fourteen components (gallic acid, chebulic acid, 1,6-di-O-galloyl-D-glucose, punicalagin, 3,4,6-tri-O-galloyl-D-glucose, casuarinin, chebulanin, corilagin, neochebulinic acid, terchebulin, ellagic acid, chebulagic acid, chebulinic acid, and 1,2,3,4,6-penta-O-galloyl-D-glucose) in the fruit of Terminalia chebula Retz. is described. The separation was achieved within 80 min using a binary gradient with mobile phases consisting of a pH 2.7 phosphoric acid solution and an 80% CH3CN solution. Capillary electrophoretic analyses were also attempted, and it was found that CZE (25 mM Na2B4O7, 5 mM NaH2PO4, pH 7.0) was an efficient method for the separation of gallotannins, while an MEKC method (25 mM Na2B4O7, 5 mM NaH2PO4, 20 mM SDS, pH 7.0, and 10% acetonitrile) provided a better separation for most of the tannins examined. The HPLC and CE methods developed were both successfully applied to the assay of tannins in commercial samples of Chebulae Fructus.

  3. Chitosan oligosaccharide induces resistance to Tobacco mosaic virus in Arabidopsis via the salicylic acid-mediated signalling pathway

    PubMed Central

    Jia, Xiaochen; Meng, Qingshan; Zeng, Haihong; Wang, Wenxia; Yin, Heng

    2016-01-01

    Chitosan is one of the most abundant carbohydrate biopolymers in the world, and chitosan oligosaccharide (COS), which is prepared from chitosan, is a plant immunity regulator. The present study aimed to validate the effect of COS on inducing resistance to tobacco mosaic virus (TMV) in Arabidopsis and to investigate the potential defence-related signalling pathways involved. Optimal conditions for the induction of TMV resistance in Arabidopsis were COS pretreatment at 50 mg/L for 1 day prior to inoculation with TMV. Multilevel indices, including phenotype data, and TMV coat protein expression, revealed that COS induced TMV resistance in wild-type and jasmonic acid pathway- deficient (jar1) Arabidopsis plants, but not in salicylic acid pathway deficient (NahG) Arabidopsis plants. Quantitative-PCR and analysis of phytohormone levels confirmed that COS pretreatment enhanced the expression of the defence-related gene PR1, which is a marker of salicylic acid signalling pathway, and increased the amount of salicylic acid in WT and jar1, but not in NahG plants. Taken together, these results confirm that COS induces TMV resistance in Arabidopsis via activation of the salicylic acid signalling pathway. PMID:27189192

  4. Chitosan oligosaccharide induces resistance to Tobacco mosaic virus in Arabidopsis via the salicylic acid-mediated signalling pathway.

    PubMed

    Jia, Xiaochen; Meng, Qingshan; Zeng, Haihong; Wang, Wenxia; Yin, Heng

    2016-05-18

    Chitosan is one of the most abundant carbohydrate biopolymers in the world, and chitosan oligosaccharide (COS), which is prepared from chitosan, is a plant immunity regulator. The present study aimed to validate the effect of COS on inducing resistance to tobacco mosaic virus (TMV) in Arabidopsis and to investigate the potential defence-related signalling pathways involved. Optimal conditions for the induction of TMV resistance in Arabidopsis were COS pretreatment at 50 mg/L for 1 day prior to inoculation with TMV. Multilevel indices, including phenotype data, and TMV coat protein expression, revealed that COS induced TMV resistance in wild-type and jasmonic acid pathway- deficient (jar1) Arabidopsis plants, but not in salicylic acid pathway deficient (NahG) Arabidopsis plants. Quantitative-PCR and analysis of phytohormone levels confirmed that COS pretreatment enhanced the expression of the defence-related gene PR1, which is a marker of salicylic acid signalling pathway, and increased the amount of salicylic acid in WT and jar1, but not in NahG plants. Taken together, these results confirm that COS induces TMV resistance in Arabidopsis via activation of the salicylic acid signalling pathway.

  5. Alexander Kapp--The First Known User of the Andragogy Concept

    ERIC Educational Resources Information Center

    Loeng, Svein

    2017-01-01

    The German gymnasium teacher Alexander Kapp (1800-1869) was to all appearances the first one to use the "andragogy concept" as a term for "adult learning." In 1833 he published the book "Platon's Erziehungslehre, als Pädagogik für die Einzelnen und als Staatspädagogik. Oder dessen praktische Philosophie." This book…

  6. "Dancing Cannot Start Too Soon": Spiritual Education in the Thought of Jean Paul Friedrich Richter

    ERIC Educational Resources Information Center

    Pridmore, John

    2004-01-01

    Johann Paul Friedrich Richter (1763-1825) adopted the pen-name "Jean Paul" in honour of Jean Jaques Rousseau. His "Levana or the doctrine of education" ("Levana oder Erziehlehre") was once a standard text and required reading in teacher education. Outside Germany the name of Jean Paul is now little known and the…

  7. INVESTIGATION OF ARSENIC SPECIATION ON DRINKING WATER TREATMENT MEDIA UTILIZING AUTOMATED SEQUENTIAL CONTINUOUS FLOW EXTRACTION WITH IC-ICP-MS DETECTION

    EPA Science Inventory

    Three treatment media, used for the removal of arsenic from drinking water, were sequentially extracted using 10mM MgCl2 (pH 8), 10mM NaH2PO4 (pH 7) followed by 10mM (NH4)2C2O4 (pH 3). The media were extracted using an on-line automated continuous extraction system which allowed...

  8. A Versatile Low Temperature Synthetic Route to Zintl Phase Precursors: Na4Si4, Na4Ge4 and K4Ge4 as Examples

    PubMed Central

    Ma, Xuchu; Xu, Fen; Atkins, Tonya; Goforth, Andrea M.; Neiner, Doinita; Navrotsky, Alexandra; Kauzlarich, Susan M.

    2010-01-01

    Na4Si4 and Na4Ge4 are ideal chemical precursors for inorganic clathrate structures, clusters, and nanocrystals. The monoclinic Zintl phases, Na4Si4 and Na4Ge4, contain isolated homo-tetrahedranide [Si4]4− and [Ge4]4− clusters surrounded by alkali metal cations. In this study, a simple scalable route has been applied to prepare Zintl phases of composition Na4Si4 and Na4Ge4 using the reaction between NaH and Si or Ge at low temperature (420 °C for Na4Si4 and 270 °C for Na4Ge4). The method was also applied to K4Ge4, using KH and Ge as raw materials, to show the versatility of this approach. The influence of specific reaction conditions on the purity of these Zintl phases has been studied by controlling five factors: the method of reagent mixing (manual or ball milled), the stoichiometry between raw materials, the reaction temperature, the heating time and the gas flow rate. Moderate ball-milling and excess NaH or KH facilitate the formation of pure Na4Si4, Na4Ge4 or K4Ge4 at 420 °C (Na4Si4) or 270 °C (both M4Ge4 compounds, M = Na, K). TG/DSC analysis of the reaction of NaH and Ge indicates that ball milling reduces the temperature for reaction and confirms the formation temperature. This method provides large quantities of high quality Na4Si4 and Na4Ge4 without the need for specialized laboratory equipment, such as Schlenk lines, niobium/tantalum containers, or an arc welder, thereby expanding the accessibility and chemical utility of these phases by making them more convenient to prepare. This new synthetic method may also be extended to lithium-containing Zintl phases (LiH is commercially available) as well as to alkali metal-tetrel Zintl compounds of other compositions, e.g. K4Ge9. PMID:19921060

  9. Role of two-sided crosstalk between NO and H2S on improvement of mineral homeostasis and antioxidative defense in Sesamum indicum under lead stress.

    PubMed

    Amooaghaie, Rayhaneh; Zangene-Madar, Faezeh; Enteshari, Shekoofeh

    2017-05-01

    H 2 S and NO are two important gasotransmitters that modulate stress responses in plants. There are the contradictory data on crosstalk between NO and H 2 S in the studies. Hence, in the present study, the role of interplay between NO and H 2 S was assessed on the Pb tolerance of Sesamum indicum using pharmacological and biochemical approaches. Results revealed that Pb stress reduced the plant growth and the content of photosynthetic pigments and Fv/Fm ratio, increased the lipid peroxidation and the H 2 O 2 content, elevated the endogenous contents of nitric oxide (NO), H 2 S and enhanced the activities of antioxidant enzymes (except APX). Additionally, concentrations of most mineral ions (K, P, Mg, Fe, Mn and Zn) in both shoots and roots decreased. Pb accumulation in roots was more than it in shoots. Both sodium hydrosulfide (NaHS as a donor of H 2 S) and sodium nitroprusside (SNP as an NO donor) improved the plant growth, the chlorophyll and carotenoid contents and PSII efficiency, reduced oxidative damage, increased the activities of antioxidant enzymes and reduced the proline content in Pb-stressed plants. Furthermore, both NaHS and SNP significantly restricted the uptake and translocation of Pb, thereby minimizing antagonistic effects of Pb on essential mineral contents in sesame plants. NaHS increased the NO generation and many NaHS-induced responses were completely reversed by cPTIO, as the specific NO scavenger. Applying SNP also enhanced H 2 S release levels in roots of Pb-stressed plants and only some NO-driven effects were partially weakened by hypotuarine (HT), as the scavenger of H 2 S.These findings proposed for the first time that two-sided interplay between H 2 S and NO might confer an increased tolerance to Pb stress via activating the antioxidant systems, reducing the uptake and translocation of Pb, and harmonizing the balance of mineral nutrient. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Hydrogen sulfide induces systemic tolerance to salinity and non-ionic osmotic stress in strawberry plants through modification of reactive species biosynthesis and transcriptional regulation of multiple defence pathways

    PubMed Central

    Christou, Anastasis; Manganaris, George A.; Papadopoulos, Ioannis; Fotopoulos, Vasileios

    2013-01-01

    Hydrogen sulfide (H2S) has been recently found to act as a potent priming agent. This study explored the hypothesis that hydroponic pretreatment of strawberry (Fragaria × ananassa cv. Camarosa) roots with a H2S donor, sodium hydrosulfide (NaHS; 100 μM for 48h), could induce long-lasting priming effects and tolerance to subsequent exposure to 100mM NaCI or 10% (w/v) PEG-6000 for 7 d. Hydrogen sulfide pretreatment of roots resulted in increased leaf chlorophyll fluorescence, stomatal conductance and leaf relative water content as well as lower lipid peroxidation levels in comparison with plants directly subjected to salt and non-ionic osmotic stress, thus suggesting a systemic mitigating effect of H2S pretreatment to cellular damage derived from abiotic stress factors. In addition, root pretreatment with NaHS resulted in the minimization of oxidative and nitrosative stress in strawberry plants, manifested via lower levels of synthesis of NO and H2O2 in leaves and the maintenance of high ascorbate and glutathione redox states, following subsequent salt and non-ionic osmotic stresses. Quantitative real-time RT-PCR gene expression analysis of key antioxidant (cAPX, CAT, MnSOD, GR), ascorbate and glutathione biosynthesis (GCS, GDH, GS), transcription factor (DREB), and salt overly sensitive (SOS) pathway (SOS2-like, SOS3-like, SOS4) genes suggests that H2S plays a pivotal role in the coordinated regulation of multiple transcriptional pathways. The ameliorative effects of H2S were more pronounced in strawberry plants subjected to both stress conditions immediately after NaHS root pretreatment, rather than in plants subjected to stress conditions 3 d after root pretreatment. Overall, H2S-pretreated plants managed to overcome the deleterious effects of salt and non-ionic osmotic stress by controlling oxidative and nitrosative cellular damage through increased performance of antioxidant mechanisms and the coordinated regulation of the SOS pathway, thus proposing a novel

  11. Novel Bacillus subtilis IND19 cell factory for the simultaneous production of carboxy methyl cellulase and protease using cow dung substrate in solid-substrate fermentation.

    PubMed

    Vijayaraghavan, Ponnuswamy; Arun, Arumugaperumal; Al-Dhabi, Naif Abdullah; Vincent, Samuel Gnana Prakash; Arasu, Mariadhas Valan; Choi, Ki Choon

    2016-01-01

    Hydrolytic enzymes, such as cellulases and proteases, have various applications, including bioethanol production, extraction of fruit and vegetable juice, detergent formulation, and leather processing. Solid-substrate fermentation has been an emerging method to utilize low-cost agricultural residues for the production of these enzymes. Although the production of carboxy methyl cellulase (CMCase) and protease in solid state fermentation (SSF) have been studied extensively, research investigating multienzyme production in a single fermentation process is limited. The production of multienzymes from a single fermentation system could reduce the overall production cost of enzymes. In order to achieve enhanced production of enzymes, the response surface methodology (RSM) was applied. Bacillus subtilis IND19 utilized cow dung substrates for the production of CMCase and protease. A central composite design and a RSM were used to determine the optimal concentrations of peptone, NaH2PO4, and medium pH. Maximum productions of CMCase and protease were observed at 0.9 % peptone, 0.78 % NaH2PO4, and medium pH of 8.41, and 1 % peptone, 0.72 % NaH2PO4, and medium pH of 8.11, respectively. Under the optimized conditions, the experimental yield of CMCase and protease reached 473.01 and 4643 U/g, which were notably close to the predicted response (485.05 and 4710 U/g). These findings corresponded to an overall increase of 2.1- and 2.5-fold in CMCase and protease productions, respectively. Utilization of cow dung for the production of enzymes is critical to producing multienzymes in a single fermentation step. Cow dung is available in large quantity throughout the year. This report is the first to describe simultaneous production of CMCase and protease using cow dung. This substrate could be directly used as the culture medium without any pretreatment for the production of these enzymes at an industrial scale.

  12. The phn Genes of Burkholderia sp. Strain RP007 Constitute a Divergent Gene Cluster for Polycyclic Aromatic Hydrocarbon Catabolism

    PubMed Central

    Laurie, Andrew D.; Lloyd-Jones, Gareth

    1999-01-01

    Cloning and molecular ecological studies have underestimated the diversity of polycyclic aromatic hydrocarbon (PAH) catabolic genes by emphasizing classical nah-like (nah, ndo, pah, and dox) sequences. Here we report the description of a divergent set of PAH catabolic genes, the phn genes, which although isofunctional to the classical nah-like genes, show very low homology. This phn locus, which contains nine open reading frames (ORFs), was isolated on an 11.5-kb HindIII fragment from phenanthrene-degrading Burkholderia sp. strain RP007. The phn genes are significantly different in sequence and gene order from previously characterized genes for PAH degradation. They are transcribed by RP007 when grown at the expense of either naphthalene or phenanthrene, while in Escherichia coli the recombinant phn enzymes have been shown to be capable of oxidizing both naphthalene and phenanthrene to predicted metabolites. The locus encodes iron sulfur protein α and β subunits of a PAH initial dioxygenase but lacks the ferredoxin and reductase components. The dihydrodiol dehydrogenase of the RP007 pathway, PhnB, shows greater similarity to analogous dehydrogenases from described biphenyl pathways than to those characterized from naphthalene/phenanthrene pathways. An unusual extradiol dioxygenase, PhnC, shows no similarity to other extradiol dioxygenases for naphthalene or biphenyl oxidation but is the first member of the recently proposed class III extradiol dioxygenases that is specific for polycyclic arene diols. Upstream of the phn catabolic genes are two putative regulatory genes, phnR and phnS. Sequence homology suggests that phnS is a LysR-type transcriptional activator and that phnR, which is divergently transcribed with respect to phnSFECDAcAdB, is a member of the ς54-dependent family of positive transcriptional regulators. Reverse transcriptase PCR experiments suggest that this gene cluster is coordinately expressed and is under regulatory control which may involve

  13. Impact of forecasted changes in Polish economy (2015 and 2020) on nutrient emission into the river basins.

    PubMed

    Pastuszak, Marianna; Kowalkowski, Tomasz; Kopiński, Jerzy; Stalenga, Jarosław; Panasiuk, Damian

    2014-09-15

    Poland, with its large drainage area, with 50% contribution of agricultural land and 45% contribution of population to overall agricultural land area and population number in the Baltic catchment, is the largest exporter of riverine nitrogen (N) and phosphorus (P) to the sea. The economic transition has resulted in substantial, statistically significant decline in N, P export from Polish territory to the Baltic Sea. Following the obligations arising from the Helsinki Commission (HELCOM) declarations, in the coming years, Poland is expected to reduce riverine N loads by ca. 25% and P loads by ca. 60% as referred to the average flow normalized loads recorded in 1997-2003. The aim of this paper is to estimate annual source apportioned N and P emissions into these river basins in 2015 and 2020 with application of modeling studies (MONERIS). Twelve scenarios, encompassing changes in anthropogenic (diffuse, point source) and natural pressure (precipitation, water outflow due to climate change), have been applied. Modeling outcome for the period 2003-2008 served as our reference material. In applied scenarios, N emission into the Oder basin in 2015 and 2020 shows an increase from 4.2% up to 9.1% as compared with the reference period. N emission into the Vistula basin is more variable and shows an increase by max. 17.8% or a decrease by max. 4.7%, depending on the scenario. The difference between N emission into the Oder and Vistula basins is related to the catchment peculiarities and handling of point sources emission. P emission into both basins shows identical scenario patters and a maximum decrease reaches 17.8% in the Oder and 16.7% in the Vistula basin. Despite a declining tendency in P loads in both rivers in all the scenarios, HELCOM targeted P load reduction is not feasible. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. [Hepatitis E - More than a Rare Travel-Associated Infectious Disease!

    PubMed

    Wedemeyer, Heiner

    2017-06-01

    Übertragungswege  In Deutschland infizieren sich jedes Jahr wahrscheinlich mehr als 300 000 Menschen mit dem Hepatitis-E-Virus (HEV). Die Hepatitis E ist in Mitteleuropa in der Regel eine durch den zoonotischen HEV-Genotyp-3-verursachte autochthone, d. h. lokal erworbene Infektionskrankheit. Der Verzehr von nicht ausreichend erhitztem Schweine- oder Wildfleisch ist ein Hauptrisikofaktor für HEV-Infektionen, Übertragungen des Virus durch Bluttransfusionen sind aber auch möglich. Diagnostik  Bei Immunkompetenten kann die Diagnose einer akuten Hepatitis E mit dem Nachweis von anti-HEV-IgM gestellt werden. Serologische Tests können bei Immunsupprimierten aber falsch-negativ sein, weshalb in diesen Fällen eine HEV-Infektion nur durch den direkten Nachweis des Erregers mittels PCR im Blut oder Stuhl erfolgen sollte. Natürlicher Verlauf  Eine akute Hepatitis E kann bei Patienten mit anderen chronischen Lebererkrankungen zu einem Leberversagen führen. Chronische Verläufe, definiert durch eine Virämie von mind. 3 Monaten, sind bei Organtransplantierten mit immunsuppressiver Medikation beschrieben, können aber auch bei anderen Immundefizienzen auftreten. Eine chronische Hepatitis E kann innerhalb von Monaten zu einer fortgeschrittenen Leberfibrose oder zur Zirrhose führen. Extrahepatische Manifestationen  Extrahepatische Manifestationen können während und nach einer HEV-Infektion auftreten. Insbesondere Guillain-Barré-Syndrome und die neuralgische Schulteramyotrophie sind mit einer Hepatitis E assoziiert worden. Therapie  Ribavirin hat eine antivirale Wirksamkeit gegen HEV. Bei chronischer Hepatitis E sollte die Behandlung für 3 – 6 Monate durchgeführt werden. Therapieversagen und Rückfälle nach Beendigung einer Behandlung sind möglich. Ein Impfstoff gegen HEV ist bisher nur in China zugelassen.

  15. Botany and the Taming of Female Passion: Rousseau and Contemporary Educational Concepts of Young Women

    ERIC Educational Resources Information Center

    Kleinau, Elke

    2012-01-01

    Central in the analyses of women's and gender studies within the history of education has been Rousseau's (Emil oder Uber die Erziehung, 12th edn. Ferdinand Schoningh, Paderborn 1762) educational novel Emile, especially Book 5, which deals with the education of Sophie, Emilie's future spouse. Given the lasting interest in the person of Rousseau…

  16. Proton-proton bremsstrahlung towards the elastic limit

    NASA Astrophysics Data System (ADS)

    Mahjour-Shafiei, M.; Amir-Ahmadi, H. R.; Bacelar, J. C. S.; Castelijns, R.; Ermisch, K.; van Garderen, E.; Gašparić, I.; Harakeh, M. N.; Kalantar-Nayestanaki, N.; Kiš, M.; Löhner, H.

    2005-05-01

    In oder to study proton-proton bremsstrahlung moving towards the elastic limit, a detection system, consisting of Plastic-ball and SALAD, was set up and an experiment at 190 MeV incident beam energy was performed. Here, the experimental setup and the data analysis procedure along with some results obtained in the measurement are discussed.

  17. Right-Wing Extremism in Germany and the Consequences for the Armed Forces (Rechtsextreme orientierungen in deutschland und ihre folgen fuer die bundeswehr)

    DTIC Science & Technology

    2001-06-01

    nicht kompati- bel" ( Findeisen /Kersten 1999: 32). In der rechtsextremen Jugendkultur k6nnten neben scheinbar ideologisch dominierten Gewaltausl6sern...Medienwirksamkeit der vorgetragenen ,,nhalte" Bertick- sicbtigung finden ( Findeisen /Kersten 1999: 32f.). Beztiglich ibrer identit~tsstiftenden Elemente...Pfahl-Traughber 1999b: 14 69ff.; Findeisen /Kersten 1999: 28f.). Familidre oder gesellschaftliche Desintegration, Arbeitslosigkeit, mangeindes

  18. Verknüpfung von DQ-Indikatoren mit KPIs und Auswirkungen auf das Return on Investment

    NASA Astrophysics Data System (ADS)

    Block, Frank

    Häufig ist nicht klar, welche Beziehungen zwischen Datenqualitätsindikatoren (DQI, Definition folgt weiter unten) und Key Performance Indicators (KPI, s. Abschnitt 1.3 für weitere Details) eines Unternehmens oder einer Organisation bestehen. Dies ist insbesondere deshalb von Bedeutung, da die Kenntnis dieser Beziehungen maßgeblich die Ausprägung eines Datenqualitätsprojekts beeinflusst.

  19. Creative and Tactile Astronomy: Exploring the Universe Using All the Senses

    ERIC Educational Resources Information Center

    Borges, Isabel; Canas, Lina; Alexander, Alison; Wiltsher, Ruth

    2015-01-01

    Creative and Tactile Astronomy is an educational project developed by English and Portuguese teachers. Isabel Borges and Lina Canas from Portugal and Alison Alexander and Ruth Wiltsher from the United Kingdom met for the first time at the 2013 Science on Stage Festival in Slubice-Oder, on the border between Germany and Poland. As a consequence of…

  20. Aus Wirtschaft und Betrieb. Biomasse: Gewinnung und Verarbeitung mit Profilschal-maschinen

    Treesearch

    P. Koch

    1977-01-01

    1963 wurden in den Südstaaten der USA nur 30% der oberund unterirdischen Biomasse der geernteten sog. Southern pines für Schnittholz und Zellstoff verwertet bzw. als getrockneies, gehobletes und abgelängtes Schnittholz oder als Kraftpapier verkauft. Keine der zusammen mit den Kiefern vorkommenden Laubholzarten wurde bisher in nennenswertem Umfan verwertet. Auch heute...

  1. Molecular Ecology of Bacterial Populations in Environmental Hazardous Chemical Control

    DTIC Science & Technology

    1991-11-30

    Reactor Figure 1. A schematic drawing of the bioreactor system for on-line studies of naphthalene degradation and light production by bioluminescent...the bioluminescent monitoring section. The reactor system consisted of a L. H. Fermentation Series 500 continuous flow bioreactor with a 1 L glass... studied the expression of the upper pathway operon of NAH7. Light induction in response to naphthalene in the strain HK44 was comparable in both

  2. Effect of Mixed Culture Growth Conditions on the Cellular Fatty Acids of Streptococci (Analyzed by High Performance Liquid Chromatography),

    DTIC Science & Technology

    1980-10-16

    mixed culture with Streptococcus S mutans , Streptococcus singuis Staphylococcus aureus,*and Escheric ia coi 1 - sA -DoWed n o quaI It atfI ve -c nah...of both S. mutans and S. scnguis. I 4 |I KEY WORDS: Fatty Acids . High Performance Liquid Chromatography Mixed Bacterial Cultures Streptococcus sal...AND METHODS Streptococcus mutans (ATCC 25175), Streptococcus sanguis (ATCC 10557), Staphylococcus aureus (ATCC 25923) and Escherichia coli (ATCC 25922

  3. Gas-liquid interface-mediated room-temperature synthesis of "clean" PdNiP alloy nanoparticle networks with high catalytic activity for ethanol oxidation.

    PubMed

    Wang, Rongfang; Ma, Yuanyuan; Wang, Hui; Key, Julian; Ji, Shan

    2014-11-04

    PdNiP alloy nanoparticle networks (PdNiP NN) were prepared by simultaneous reduction of PdCl2, NiCl2 and NaH2PO2 with NaBH4via a gas-liquid interface reaction at room temperature using N2 bubbles. PdNiP NN had markedly higher activity and durability for ethanol oxidation than PdNi nanoparticle networks and PdNiP grain aggregates.

  4. Rules of Engagement - 1 January 1966 - 1 November 1969

    DTIC Science & Technology

    1969-08-31

    1976 auanc:T: O.owngrading of Project CIIECO Report TO: AAC ADC AFAFC AFLC ( Historian ) AFRES AFSC ATC All t-IAC PACAF SAC TAC USA FE...Z. p󈧙·•k. , ~. t ~ s ipso [aoto a moto ¥>ab?.~ road or· naH. Sc.. an!:fpt-:.~.-.:r,: th:..tt !fOU find a veh-;.cle~ d .;·( .~a’l a5JIOI~ th:u 1

  5. Identification of source velocities on 3D structures in non-anechoic environments: Theoretical background and experimental validation of the inverse patch transfer functions method

    NASA Astrophysics Data System (ADS)

    Aucejo, M.; Totaro, N.; Guyader, J.-L.

    2010-08-01

    In noise control, identification of the source velocity field remains a major problem open to investigation. Consequently, methods such as nearfield acoustical holography (NAH), principal source projection, the inverse frequency response function and hybrid NAH have been developed. However, these methods require free field conditions that are often difficult to achieve in practice. This article presents an alternative method known as inverse patch transfer functions, designed to identify source velocities and developed in the framework of the European SILENCE project. This method is based on the definition of a virtual cavity, the double measurement of the pressure and particle velocity fields on the aperture surfaces of this volume, divided into elementary areas called patches and the inversion of impedances matrices, numerically computed from a modal basis obtained by FEM. Theoretically, the method is applicable to sources with complex 3D geometries and measurements can be carried out in a non-anechoic environment even in the presence of other stationary sources outside the virtual cavity. In the present paper, the theoretical background of the iPTF method is described and the results (numerical and experimental) for a source with simple geometry (two baffled pistons driven in antiphase) are presented and discussed.

  6. Aldosterone interaction with epidermal growth factor receptor signaling in MDCK cells.

    PubMed

    Gekle, Michael; Freudinger, Ruth; Mildenberger, Sigrid; Silbernagl, Stefan

    2002-04-01

    Epidermal growth factor (EGF) regulates cell proliferation, differentiation, and ion transport by using extracellular signal-regulated kinase (ERK)1/2 as a downstream signal. Furthermore, the EGF-receptor (EGF-R) is involved in signaling by G protein-coupled receptors, growth hormone, and cytokines by means of transactivation. It has been suggested that steroids interact with peptide hormones, in part, by rapid, potentially nongenomic, mechanisms. Previously, we have shown that aldosterone modulates Na(+)/H(+) exchange in Madin-Darby canine kidney (MDCK) cells by means of ERK1/2 in a way similar to growth factors. Here, we tested the hypothesis that aldosterone uses the EGF-R as a heterologous signal transducer in MDCK cells. Nanomolar concentrations of aldosterone induce a rapid increase in ERK1/2 phosphorylation, cellular Ca(2+) concentration, and Na(+)/H(+) exchange activity similar to increases induced by EGF. Furthermore, aldosterone induced a rapid increase in EGF-R-Tyr phosphorylation, and inhibition of EGF-R kinase abolished aldosterone-induced signaling. Inhibition of ERK1/2 phosphorylation reduced the Ca(2+) response, whereas prevention of Ca(2+) influx did not abolish ERK1/2 phosphorylation. Our data show that aldosterone uses the EGF-R-ERK1/2 signaling cascade to elicit its rapid effects in MDCK cells.

  7. Distribution of petroleum degrading genes and factor analysis of petroleum contaminated soil from the Dagang Oilfield, China

    PubMed Central

    Liu, Qinglong; Tang, Jingchun; Bai, Zhihui; Hecker, Markus; Giesy, John P.

    2015-01-01

    Genes that encode for enzymes that can degrade petroleum hydrocarbons (PHs) are critical for the ability of microorganisms to bioremediate soils contaminated with PHs. Distributions of two petroleum-degrading genes AlkB and Nah in soils collected from three zones of the Dagang Oilfield, Tianjin, China were investigated. Numbers of copies of AlkB ranged between 9.1 × 105 and 1.9 × 107 copies/g dry mass (dm) soil, and were positively correlated with total concentrations of PHs (TPH) (R2 = 0.573, p = 0.032) and alkanes (C33 ~ C40) (R2 = 0.914, p < 0.01). The Nah gene was distributed relatively evenly among sampling zones, ranging between 1.9 × 107 and 1.1 × 108 copies/g dm soil, and was negatively correlated with concentrations of total aromatic hydrocarbons (TAH) (R2 = −0.567, p = 0.035) and ∑16 PAHs (R2 = −0.599, p = 0.023). Results of a factor analysis showed that individual samples of soils were not ordinated as a function of the zones. PMID:26086670

  8. A benign synthesis of alane by the composition-controlled mechanochemical reaction of sodium hydride and aluminum chloride

    DOE PAGES

    Hlova, Ihor; Goldston, Jennifer F.; Gupta, Shalabh; ...

    2017-05-30

    Solid-state mechanochemical synthesis of alane (AlH 3) starting from sodium hydride (NaH) and aluminum chloride (AlCl 3) has been achieved at room temperature. The transformation pathway of this solid-state reaction was controlled by a stepwise addition of AlCl 3 to the initial reaction mixture that contained sodium hydride in excess of stoichiometric amount. As in the case of previously investigated LiH–AlCl 3 system, complete selectivity was achieved whereby formation of unwanted elemental aluminum was fully suppressed, and AlH 3 was obtained in quantitative yield. Reaction progress during each step was investigated by means of solid-state NMR and powder X-ray diffraction,more » which revealed that the overall reaction proceeds through a series of intermediate alanates that may be partially chlorinated. The NaH–AlCl 3 system presents some subtle differences compared to LiH–AlCl 3 system particularly with respect to optimal concentrations needed during one of the reaction stages. Based on the results, we postulate that high local concentrations of NaH may stabilize chlorine-containing derivatives and prevent decomposition into elemental aluminum with hydrogen evolution. As a result, complete conversion with quantitative yield of alane was confirmed by both SSNMR and hydrogen desorption analysis.« less

  9. Occurrence and diversity of naphthalene dioxygenase genes in soil microbial communities from the Maritime Antarctic.

    PubMed

    Flocco, Cecilia G; Gomes, Newton C M; Mac Cormack, Walter; Smalla, Kornelia

    2009-03-01

    The diversity of naphthalene dioxygenase genes (ndo) in soil environments from the Maritime Antarctic was assessed, dissecting as well the influence of the two vascular plants that grow in the Antarctic: Deschampsia antarctica and Colobanthus quitensis. Total community DNA was extracted from bulk and rhizosphere soil samples from Jubany station and Potter Peninsula, South Shetland Islands. ndo genes were amplified by a nested PCR and analysed by denaturant gradient gel electrophoresis approach (PCR-DGGE) and cloning and sequencing. The ndo-DGGE fingerprints of oil-contaminated soil samples showed even and reproducible patterns, composed of four dominant bands. The presence of vascular plants did not change the relative abundance of ndo genotypes compared with bulk soil. For non-contaminated sites, amplicons were not obtained for all replicates and the variability among the fingerprints was comparatively higher, likely reflecting a lower abundance of ndo genes. The phylogenetic analyses showed that all sequences were affiliated to the nahAc genes closely related to those described for Pseudomonas species and related mobile genetic elements. This study revealed that a microdiversity of nahAc-like genes exists in microbial communities of Antarctic soils and quantitative PCR indicated that their relative abundance was increased in response to anthropogenic sources of pollution.

  10. Ixeris dentata extract regulates salivary secretion through the activation of aquaporin-5 and prevents diabetes-induced xerostomia

    PubMed Central

    Bhattarai, Kashi Raj; Lee, Sang-Won; Kim, Seung Hyun; Kim, Hyung-Ryong; Chae, Han-Jung

    2017-01-01

    The aim of this study was to investigate the effects of Ixeris dentata (IXD) extract to improve the salivation rate in dry mouth induced by diabetes. Both control and diabetic rats were treated with a sublingual spray of either water or IXD extract to determine the effects of IXD on salivation. During the study, we observed that IXD extract treatment increased the salivary flow rate in diabetic rats. The expression of α-amylase was increased significantly in both saliva and glandular tissue lysates of IXD-treated diabetic rats. Aquaporin-5 protein expression was abnormally low in the salivary glands of diabetic rats, which increased hyposalivation and led to salivary dysfunction. However, a single oral spray of IXD extract drastically increased the expression of aquaporin-5 in salivary gland acinar and ductal cells in diabetic rats. Moreover, IXD extract induced expression of Na+/H+ exchangers in the salivary gland, which suggests that Na+/H+ exchangers modulate salivary secretions and aid in the fluid-secretion mechanism. Furthermore, transient treatment with IXD extract increased the intracellular calcium in human salivary gland cells. Taken together, these results suggest the potential value of an IXD extract for the treatment of diabetes-induced hyposalivation and xerostomia. PMID:28814903

  11. A benign synthesis of alane by the composition-controlled mechanochemical reaction of sodium hydride and aluminum chloride

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hlova, Ihor; Goldston, Jennifer F.; Gupta, Shalabh

    Solid-state mechanochemical synthesis of alane (AlH 3) starting from sodium hydride (NaH) and aluminum chloride (AlCl 3) has been achieved at room temperature. The transformation pathway of this solid-state reaction was controlled by a stepwise addition of AlCl 3 to the initial reaction mixture that contained sodium hydride in excess of stoichiometric amount. As in the case of previously investigated LiH–AlCl 3 system, complete selectivity was achieved whereby formation of unwanted elemental aluminum was fully suppressed, and AlH 3 was obtained in quantitative yield. Reaction progress during each step was investigated by means of solid-state NMR and powder X-ray diffraction,more » which revealed that the overall reaction proceeds through a series of intermediate alanates that may be partially chlorinated. The NaH–AlCl 3 system presents some subtle differences compared to LiH–AlCl 3 system particularly with respect to optimal concentrations needed during one of the reaction stages. Based on the results, we postulate that high local concentrations of NaH may stabilize chlorine-containing derivatives and prevent decomposition into elemental aluminum with hydrogen evolution. As a result, complete conversion with quantitative yield of alane was confirmed by both SSNMR and hydrogen desorption analysis.« less

  12. Sodic alkaline stress mitigation by interaction of nitric oxide and polyamines involves antioxidants and physiological strategies in Solanum lycopersicum.

    PubMed

    Gong, Biao; Li, Xiu; Bloszies, Sean; Wen, Dan; Sun, Shasha; Wei, Min; Li, Yan; Yang, Fengjuan; Shi, Qinghua; Wang, Xiufeng

    2014-06-01

    Nitric oxide (NO) and polyamines (PAs) are two kinds of important signal in mediating plant tolerance to abiotic stress. In this study, we observed that both NO and PAs decreased alkaline stress in tomato plants, which may be a result of their role in regulating nutrient balance and reactive oxygen species (ROS), thereby protecting the photosynthetic system from damage. Further investigation indicated that NO and PAs induced accumulation of each other. Furthermore, the function of PAs could be removed by a NO scavenger, cPTIO. On the other hand, application of MGBG, a PA synthesis inhibitor, did little to abolish the function of NO. To further elucidate the mechanism by which NO and PAs alleviate alkaline stress, the expression of several genes associated with abiotic stress was analyzed by qRT-PCR. NO and PAs significantly upregulated ion transporters such as the plasma membrane Na(+)/H(+) antiporter (SlSOS1), vacuolar Na(+)/H(+) exchanger (SlNHX1 and SlNHX2), and Na(+) transporter and signal components including ROS, MAPK, and Ca(2+) signal pathways, as well as several transcription factors. All of these play important roles in plant adaptation to stress conditions. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Optimization of Medium Using Response Surface Methodology for Lipid Production by Scenedesmus sp.

    PubMed Central

    Yang, Fangfang; Long, Lijuan; Sun, Xiumei; Wu, Hualian; Li, Tao; Xiang, Wenzhou

    2014-01-01

    Lipid production is an important indicator for assessing microalgal species for biodiesel production. In this work, the effects of medium composition on lipid production by Scenedesmus sp. were investigated using the response surface methodology. The results of a Plackett–Burman design experiment revealed that NaHCO3, NaH2PO4·2H2O and NaNO3 were three factors significantly influencing lipid production, which were further optimized by a Box–Behnken design. The optimal medium was found to contain 3.07 g L−1 NaHCO3, 15.49 mg L−1 NaH2PO4·2H2O and 803.21 mg L−1 NaNO3. Using the optimal conditions previously determined, the lipid production (304.02 mg·L−1) increased 54.64% more than that using the initial medium, which agreed well with the predicted value 309.50 mg L−1. Additionally, lipid analysis found that palmitic acid (C16:0) and oleic acid (C18:1) dominantly constituted the algal fatty acids (about 60% of the total fatty acids) and a much higher content of neutral lipid accounted for 82.32% of total lipids, which strongly proved that Scenedesmus sp. is a very promising feedstock for biodiesel production. PMID:24663113

  14. Complementary action of jasmonic acid on salicylic acid in mediating fungal elicitor-induced flavonol glycoside accumulation of Ginkgo biloba cells.

    PubMed

    Xu, Maojun; Dong, Jufang; Wang, Huizhong; Huang, Luqi

    2009-08-01

    The antagonistic action between jasmonic acid (JA) and salicylic acid (SA) in plant defence responses has been well documented. However, their relationship in secondary metabolite production is largely unknown. Here, we report that PB90, a protein elicitor from Phytophthora boehmeriae, triggers JA generation, SA accumulation and flavonol glycoside production of Ginkgo biloba cells. JA inhibitors suppress not only PB90-triggered JA generation, but also the elicitor-induced flavonol glycoside production. However, the elicitor can still enhance flavonol glycoside production even though the JA generation is totally inhibited. Over-expression of SA hydrolase gene NahG not only abolishes SA accumulation, but also suppresses the elicitor-induced flavonol glycoside production when JA signalling is inhibited. Interestingly, expression of NahG does not inhibit the elicitor-induced flavonol glycoside accumulation in the absence of JA inhibitors. Moreover, JA levels are significantly enhanced when SA accumulation is impaired in the transgenic cells. Together, the data suggest that both JA and SA are involved in PB90-induced flavonol glycoside production. Furthermore, we demonstrate that JA signalling might be enhanced to substitute for SA to mediate the elicitor-induced flavonol glycoside accumulation when SA signalling is impaired, which reveals an unusual complementary relationship between JA and SA in mediating plant secondary metabolite production.

  15. Energy Distributions of Neutrons Scattered from Graphite, Light and Heavy Water, Ice, Zirconium Hydride, Lithium Hydride, Sodium Hydride and Ammonium Chloride by the Beryllium Detector Method

    DOE R&D Accomplishments Database

    Woods, A. D. B.; Brockhouse, Bertram N.; Sakamoto, M.; Sinclair, R. N.

    1960-09-12

    Energy distributions of neutrons scattered from various moderators and from several hydrogenous substances were measured at energy transfers of 0.02 to 0.24 ev. Results from experiments on graphite, light and heavy water, ice, ZrH, LiH, NaH, and NH4Cl are included. It is noted that the results are of a preliminary character; however, they are probably the most accurate measurements of high-energy transfers yet made. (J.R.D.)

  16. Recapitalizing Nuclear Weapons (Walker Paper, Number 8)

    DTIC Science & Technology

    2007-08-01

    Sandia National Laboratories, with cam- puses in California and New Mexico), four production plants (the Pantex Plant in Amarillo, TX; the Y-12 Plant in...Oak Ridge, TN; the Kansas City Plant in Kansas City, MO; and the Savan- nah River Site in Savannah River, SC), and the Nevada Test Site. The fall...this infrastructure (e.g., closures of Rocky Flats, Mound, and Pinellas facilities). At the same time, investments in the remaining supporting

  17. ARC-1969-AC90-0178-97

    NASA Image and Video Library

    1990-06-04

    Bell NAH-1G (USA 70-15979 NASA-736) FLITE Cobra helicopter hovering on Ames ramp is successor to the original FLITE Cobra. It has been used extensively in joint NASA/Army human factors research in the areas of night vision displays and voice communications since its arrival in 1987. Note: Used in publication in Flight Research at Ames; 57 Years of Development and Validation of Aeronautical Technology NASA SP-1998-3300 fig 140

  18. The sanitary state of Pomeranian Bay and Gulf of Gdańsk waters during the flood of 1997

    NASA Astrophysics Data System (ADS)

    Michalska, Małgorzata; Bartoszewicz, Maria

    1998-06-01

    Due to the 1997 summer flood, the Pomeranian and Gdańsk Bays were polluted with a significant amount of bacteriologically contaminated Oder and Vistula rivers waters. The purpose of this study was to determine the sanitary state of both bays during the flood and directly after it, the range of direction of distribution of the bacteriological contamination brought in by Vistula and Oder waters. On the basis of examination results, the sanitary state of the bays waters was found to be worse, particularly with regard to indicators: total bacterial number (at 20 °C and 37 °C) and Most Probable Number (MPN) of coliform and faecal coliform bacteria. Bacteria of the Pseudomonas group (Pseudomonas aeruginosa, Pseudomonas fluorescens), Enterobacteriaceae group (m.in. Proteus vulgaris), as well as enterococci (Streptoccus) and staphylococci (Staphylococcus) were found in water samples from Pomeranian and Gdańsk Bays. In the Pomeranian Bay the waters spread to the west (due to weather conditions), whereas in Gdańsk Bay they remained mainly in the coastal zone and then moved to the east. An improvement in the sanitary state of both bay waters was observed at the end of August.

  19. Salinity Tolerance of Two Potato Cultivars (Solanum tuberosum) Correlates With Differences in Vacuolar Transport Activity

    PubMed Central

    Jaarsma, Rinse; de Boer, Albertus H.

    2018-01-01

    Potato is an important cultivated crop species and since it is moderately salt sensitive there is a need to develop more salt tolerant cultivars. A high activity of Na+ transport across the tonoplast in exchange for H+ is essential to reduce Na+ toxicity. The proton motive force (PMF) generated by the V-H+-ATPase and the V-H+-PPase energizes the Na+(K+)/H+ antiport. We compared the activity, gene expression, and protein levels of the vacuolar proton pumps and the Na+/H+ antiporters in two potato cultivars (Solanum tuberosum) contrasting in their salt tolerance (cv. Desiree; tolerant and Mozart; sensitive) grown at 0 and 60 mM NaCl. Tonoplast-enriched vesicles were used to study the pump activity and protein levels of the V-H+-ATPase and the V-H+-PPase and the activity of the Na+/H+ antiporter. Although salt stress reduced the V-H+-ATPase and the V-H+-PPase activity in both cultivars, the decline in H+ pump activity was more severe in the salt-sensitive cultivar Mozart. After salt treatment, protein amounts of the vacuolar H+ pumps decreased in Mozart but remained unchanged in the cultivar Desiree. Decreased protein amounts of the V-H+-PPase found in Mozart may explain the reduced V-H+-PPase activity found for Mozart after salt stress. Under non-stress conditions, protein amounts of V-H+-PPase were equal in both cultivars while the V-H+-PPase activity was already twice as high and remained higher after salt treatment in the cultivar Desiree as compared to Mozart. This cultivar-dependent V-H+-PPase activity may explain the higher salt tolerance of Desiree. Moreover, combined with reduced vacuolar H+ pump activity, Mozart showed a lower Na+/H+ exchange activity and the Km for Na+ is at least twofold lower in tonoplast vesicles from Desiree, what suggests that NHXs from Desiree have a higher affinity for Na+ as compared to Mozart. From these results, we conclude that the higher capacity in combination with the higher affinity for Na+ uptake can be an important factor

  20. Hydrogen sulfide donors alleviate itch secondary to the activation of type-2 protease activated receptors (PAR-2) in mice.

    PubMed

    Coavoy-Sánchez, S A; Rodrigues, L; Teixeira, S A; Soares, A G; Torregrossa, R; Wood, M E; Whiteman, M; Costa, S K P; Muscará, M N

    2016-11-01

    Hydrogen sulfide (H 2 S) has been highlighted as an endogenous signaling molecule and we have previously found that it can inhibit histamine-mediated itching. Pruritus is the most common symptom of cutaneous diseases and anti-histamines are the usual treatment; however, anti-histamine-resistant pruritus is common in some clinical settings. In this way, the involvement of mediators other than histamine in the context of pruritus requires new therapeutic targets. Considering that the activation of proteinase-activated receptor 2 (PAR-2) is involved in pruritus both in rodents and humans, in this study we investigated the effect of H 2 S donors on the acute scratching behavior mediated by PAR-2 activation in mice, as well as some of the possible pharmacological mechanisms involved. The intradermal injection of the PAR-2 peptide agonist SLIGRL-NH 2 (8-80nmol) caused a dose-dependent scratching that was unaffected by intraperitoneal pre-treatment with the histamine H1 antagonist pyrilamine (30mg/kg). Co-injection of SLIGRL-NH 2 (40nmol) with either the slow-release H 2 S donor GYY4137 (1 and 3nmol) or the spontaneous donor NaHS (1 and 0.3nmol) significantly reduced pruritus. Co-treatment with the K ATP channel blocker glibenclamide (200nmol) or the nitric oxide (NO) donor sodium nitroprusside (10nmol) abolished the antipruritic effects of NaHS; however, the specific soluble guanylyl cyclase inhibitor ODQ (30μg) had no significant effects. The transient receptor potential ankyrin type 1 (TRPA1) antagonist HC-030031 (20μg) significantly reduced SLIGRL-NH 2 -induced pruritus; however pruritus induced by the TRPA1 agonist AITC (1000nmol) was unaffected by NaHS. Based on these data, we conclude that pruritus secondary to PAR-2 activation can be reduced by H 2 S, which acts through K ATP channel opening and involves NO in a cyclic guanosine monophosphate (cGMP)-independent manner. Furthermore, TRPA1 receptors mediate the pruritus induced by activation of PAR-2, but H 2 S

  1. H2S induced coma and cardiogenic shock in the rat: Effects of phenothiazinium chromophores

    PubMed Central

    SONOBE, TAKASHI; HAOUZI, PHILIPPE

    2015-01-01

    Context Hydrogen sulfide (H2S) intoxication produces an acute depression in cardiac contractility-induced circulatory failure, which has been shown to be one of the major contributors to the lethality of H2S intoxication or to the neurological sequelae in surviving animals. Methylene blue (MB), a phenothiazinium dye, can antagonize the effects of the inhibition of mitochondrial electron transport chain, a major effect of H2S toxicity. Objectives We investigated whether MB could affect the immediate outcome of H2S-induced coma in unanesthetized animals. Second, we sought to characterize the acute cardiovascular effects of MB and two of its demethylated metabolites—azure B and thionine—in anesthetized rats during lethal infusion of H2S. Materials and methods First, MB (4 mg/kg, intravenous [IV]) was administered in non-sedated rats during the phase of agonal breathing, following NaHS (20 mg/kg, IP)-induced coma. Second, in 4 groups of urethane-anesthetized rats, NaHS was infused at a rate lethal within 10 min (0.8 mg/min, IV). Whenever cardiac output (CO) reached 40% of its baseline volume, MB, azure B, thionine, or saline were injected, while sulfide infusion was maintained until cardiac arrest occurred. Results Seventy-five percent of the comatose rats that received saline (n = 8) died within 7 min, while all the 7 rats that were given MB survived (p = 0.007). In the anesthetized rats, arterial, left ventricular pressures and CO decreased during NaHS infusion, leading to a pulseless electrical activity within 530 s. MB produced a significant increase in CO and dP/dtmax for about 2 min. A similar effect was produced when MB was also injected in the pre-mortem phase of sulfide exposure, significantly increasing survival time. Azure B produced an even larger increase in blood pressure than MB, while thionine had no effect. Conclusion MB can counteract NaHS-induced acute cardiogenic shock; this effect is also produced by azure B, but not by thionine, suggesting

  2. Return to sport in Australian football league footballers after hip arthroscopy and midterm outcome.

    PubMed

    Amenabar, Tomas; O'Donnell, John

    2013-07-01

    To study the return to sport in a series of professional athletes in a single sport (Australian Rules Football), operated on arthroscopically for hip joint pathology. We performed a retrospective review of the senior author's surgical database starting in 2003. All of the patients who were Australian Football League (AFL) professional players with a minimum of 2 years' follow-up were included. Intra-articular pathologies were identified and treated. All patients were prospectively assessed with the modified Harris Hip Score (MHHS) and the Non-Arthritic Hip Score (NAHS). In addition, information about the active participation of the patients in their teams and return to professional sport was obtained from AFL registers and team physicians. Since 2003, the senior author has operated on 36 male professional AFL players; 26 of 27 with at least 2 years' follow-up were available for review. The mean age at the time of surgery was 22.1 years (range, 16 to 30 years), and 8 patients had bilateral pathology; therefore 34 hips were operated on. This report refers to those 26 players and 34 hips. All but 1 of the patients returned to play professionally. By the last survey (October 2011), 16 patients (62%) were still playing professional AFL football, and they have been playing for a mean of 52.5 months after surgery. Ten patients had retired from professional football, but they had all returned to play professionally after surgery. Only one of them retired for causes related to hip disability. There was a significant improvement in preoperative outcome scores. The MHHS and NAHS improved from 83.6 to 98 and from 85.3 to 97.1, respectively, in the players who were still playing (P < .05). Rim lesions were present in 33 hips (97%). Femoral osteochondroplasty was performed in 26 hips (76%). Arthroscopic treatment of intra-articular pathologies in professional athletes resulted in a 96% rate of return to elite-level sport and a durable increase in the MHHS and NAHS. Level IV

  3. Ebenen des Verstehens: Überlegungen zu einem Verfahren zum Wurzelziehen

    NASA Astrophysics Data System (ADS)

    Winter, Martin

    Wir bemühen uns, insbesondere bei Kindern, den Lernprozess auch im Mathematikunterricht durch den Einsatz von Materialien zu unterstützen. Die Arbeitsschritte dienen dabei oft der Vorbereitung oder Herleitung von Verfahren - in der Hoffnung, dass durch die Veranschaulichung Zusammenhänge besser verstanden werden. Worin dann das Verstehen besteht, wenn im Ergebnis ein Verfahren von den Kindern erfolgreich abgearbeitet wird, ist nicht unmittelbar zu sehen.

  4. FOCJ as a Means of Regional Cooperation (FOCJ als Mittel regionaler Kooperation)

    DTIC Science & Technology

    2008-03-01

    Zinssicherungsin- strumente wie Swap-Geschdfte und Optionsgeschdifte (Rehm 2001) sogenannte De- rivatgeschdifte sollten ffir FOCJ an die engen Voraussetzungen, die...Fehler behoben werden mUissen und auf spezielle Wilnsche des noch engen Kundenkreises eingegangen werden muss, ist der finan- zielle Aufwand fdr Forschung...selbst Cluster entwickeln, z.B. Dow Chemicals mit ,,value 57 park", oder gernischtwirtschaftlicher Unternehmen, z.B. Volkswagen" (Detig, Feng, Friedrich

  5. NMR studies on Na+ transport in Synechococcus PCC 6311

    NASA Technical Reports Server (NTRS)

    Nitschmann, W. H.; Packer, L.

    1992-01-01

    The freshwater cyanobacterium Synechococcus PCC 6311 is able to adapt to grow after sudden exposure to salt (NaCl) stress. We have investigated the mechanism of Na+ transport in these cells during adaptation to high salinity. Na+ influx under dark aerobic conditions occurred independently of delta pH or delta psi across the cytoplasmic membrane, ATPase activity, and respiratory electron transport. These findings are consistent with the existence of Na+/monovalent anion cotransport or simultaneous Na+/H+ +anion/OH- exchange. Na+ influx was dependent on Cl-, Br-, NO3-, or NO2-. No Na+ uptake occurred after addition of NaI, NaHCO3, or Na2SO4. Na+ extrusion was absolutely dependent on delta pH and on an ATPase activity and/or on respiratory electron transport. This indicates that Na+ extrusion via Na+/H+ exchange is driven by primary H+ pumps in the cytoplasmic membrane. Cells grown for 4 days in 0.5 m NaCl medium, "salt-grown cells," differ from control cells by a lower maximum velocity of Na+ influx and by lower steady-state ratios of [Na+]in/[Na+]out. These results indicate that cells grown in high-salt medium increase their capacity to extrude Na+. During salt adaptation Na+ extrusion driven by respiratory electron transport increased from about 15 to 50%.

  6. Ontogeny of NHE8 in the rat proximal tubule

    PubMed Central

    Becker, Amy M.; Zhang, Jianning; Goyal, Sunita; Dwarakanath, Vangipuram; Aronson, Peter S.; Moe, Orson W.; Baum, Michel

    2014-01-01

    Proximal tubule bicarbonate reabsorption is primarily mediated via the Na+/H+ exchanger, identified as NHE3 in adults. Previous studies have demonstrated a maturational increase in rat proximal tubule NHE3 expression, with a paucity of NHE3 expression in neonates, despite significant Na+-dependent proton secretion. Recently, a novel Na+/H+ antiporter (NHE8) was identified and found to be expressed on the apical membrane of the proximal tubule. To determine whether NHE8 may be the antiporter responsible for proton secretion in neonates, the present study characterized the developmental expression of NHE8 in rat proximal tubules. RNA blots and real-time RT-PCR demonstrated no developmental difference in the mRNA of renal NHE8. Immunoblots, however, demonstrated peak protein abundance of NHE8 in brush border membrane vesicles of 7- and 14-day-old compared with adult rats. In contrast, the level of NHE8 expression in total cortical membrane protein was higher in adults than in neonates. Immunohistochemistry confirmed the presence of NHE8 on the apical membrane of the proximal tubules of neonatal and adult rats. These data demonstrate that NHE8 does undergo maturational changes on the apical membrane of the rat proximal tubule and may account for the Na+-dependent proton flux in neonatal proximal tubules. PMID:17429030

  7. Co-overexpressing a Plasma Membrane and a Vacuolar Membrane Sodium/Proton Antiporter Significantly Improves Salt Tolerance in Transgenic Arabidopsis Plants

    PubMed Central

    Pehlivan, Necla; Sun, Li; Jarrett, Philip; Yang, Xiaojie; Mishra, Neelam; Chen, Lin; Kadioglu, Asim; Shen, Guoxin; Zhang, Hong

    2016-01-01

    The Arabidopsis gene AtNHX1 encodes a vacuolar membrane-bound sodium/proton (Na+/H+) antiporter that transports Na+ into the vacuole and exports H+ into the cytoplasm. The Arabidopsis gene SOS1 encodes a plasma membrane-bound Na+/H+ antiporter that exports Na+ to the extracellular space and imports H+ into the plant cell. Plants rely on these enzymes either to keep Na+ out of the cell or to sequester Na+ into vacuoles to avoid the toxic level of Na+ in the cytoplasm. Overexpression of AtNHX1 or SOS1 could improve salt tolerance in transgenic plants, but the improved salt tolerance is limited. NaCl at concentration >200 mM would kill AtNHX1-overexpressing or SOS1-overexpressing plants. Here it is shown that co-overexpressing AtNHX1 and SOS1 could further improve salt tolerance in transgenic Arabidopsis plants, making transgenic Arabidopsis able to tolerate up to 250 mM NaCl treatment. Furthermore, co-overexpression of AtNHX1 and SOS1 could significantly reduce yield loss caused by the combined stresses of heat and salt, confirming the hypothesis that stacked overexpression of two genes could substantially improve tolerance against multiple stresses. This research serves as a proof of concept for improving salt tolerance in other plants including crops. PMID:26985021

  8. Salicylic acid regulates basal resistance to Fusarium head blight in wheat.

    PubMed

    Makandar, Ragiba; Nalam, Vamsi J; Lee, Hyeonju; Trick, Harold N; Dong, Yanhong; Shah, Jyoti

    2012-03-01

    Fusarium head blight (FHB) is a destructive disease of cereal crops such as wheat and barley. Previously, expression in wheat of the Arabidopsis NPR1 gene (AtNPR1), which encodes a key regulator of salicylic acid (SA) signaling, was shown to reduce severity of FHB caused by Fusarium graminearum. It was hypothesized that SA signaling contributes to wheat defense against F. graminearum. Here, we show that increased accumulation of SA in fungus-infected spikes correlated with elevated expression of the SA-inducible pathogenesis-related 1 (PR1) gene and FHB resistance. In addition, FHB severity and mycotoxin accumulation were curtailed in wheat plants treated with SA and in AtNPR1 wheat, which is hyper-responsive to SA. In support of a critical role for SA in basal resistance to FHB, disease severity was higher in wheat expressing the NahG-encoded salicylate hydroxylase, which metabolizes SA. The FHB-promoting effect of NahG was overcome by application of benzo (1,2,3), thiadiazole-7 carbothioic acid S-methyl ester, a synthetic functional analog of SA, thus confirming an important role for SA signaling in basal resistance to FHB. We further demonstrate that jasmonate signaling has a dichotomous role in wheat interaction with F. graminearum, constraining activation of SA signaling during early stages of infection and promoting resistance during the later stages of infection.

  9. Nine Days to Oder: An Alternate NATO Strategy for Central Region, Europe.

    DTIC Science & Technology

    1980-06-01

    in the formulation of the air campaign plans. To all these colleagues in the profession of arms, the authors offer their thanks. ii TABLE OF CONTENTS ...Risk Assessment ...................... 144 iv TABLE OF CONTENTS CONTINUED Page XI. THE COST OF THE ALTERNATE STRATEGY ... ........... ... 149 XII. PACT...Encyclopedia of Military History, p. 261. 2. Basil Liddell Hart, The Sword and the Pen, p. 319. 3. Ibid., p. 318. 3 CHAPTER II SOVIET STRATEGY AND PACT

  10. Introduction of a Diagnosis Related Groups’ Case Flat Rate System: Hopes and Fears (einfuerhrng eines drg-fallpauschalensystems - hoffnungen und aengste)

    DTIC Science & Technology

    2000-06-01

    Anwendung und Pflege des neuen Systems dienen soil, wenn die entscheidenden Vorgaben bereits durch die Deckelung gegeben sind. Oder denkt man an den...Software und die da- mit verbundenen Lizenzgebuhren, sondern auch in der Folge um die Schulung der Mitarbeiter sowie die Pflege und Weiterentwicklung...sung an die medizinische Entwicklung" sowie von "Verfahren zur laufen- den Pflege des VergOtungssystems" gesprochen. Es mossen jedoch klare

  11. Wirkstoffe, Medikamente und Mathematische Bildverarbeitung

    NASA Astrophysics Data System (ADS)

    Bauer, Günter J.; Lorenz, Dirk A.; Maaß, Peter; Preckel, Hartwig; Trede, Dennis

    Die Entwicklung neuer Medikamente ist langwierig und teuer. Der erste Schritt ist hierbei die Suche nach neuen Wirkstoffkandidaten, die für die Behandlung bislang schwer therapierbarer Krankheiten geeignet sind. Hierfür stehen der Pharma- und Biotechnologieindustrie riesige Substanzbibliotheken zur Verfügung. In diesen Bibliotheken werden die unterschiedlichsten Substanzen gesammelt, die entweder synthetisch hergestellt oder aus Pilzen, Bakterienkulturen und anderen Lebewesen gewonnen werden können.

  12. Elektroakustische Wandler

    NASA Astrophysics Data System (ADS)

    Plaßmann, Wilfried

    Um Sprache und Musik über größere Entfernungen zu übertragen, wird der Hörschall mit einem Mikrofon in ein proportionales elektrisches Signal umgewandelt und auf drahtlosem Wege (Beispiel Rundfunkübertragung) oder drahtgebunden (Beispiel Telefon, Kabelrundfunk, oft in Kombination mit dem drahtlosen Weg) zum Empfänger übermittelt. Am Empfangsort setzt z. B. ein Lautsprecher das elektrische Signal wieder in ein akustisches Signal um.

  13. New nanotube synthesis strategy--application of sodium nanotubes formed inside anodic aluminium oxide as a reactive template.

    PubMed

    Wang, Lung-Shen; Lee, Chi-Young; Chiu, Hsin-Tien

    2003-08-07

    Formation of Na nanotubes inside the channels of anodic aluminium oxide (AAO) membranes has been achieved by decomposing NaH thermally on AAO. The as-produced material, Na@AAO, is applied as a reactive template to prepare other tubular materials. Reacting Na@AAO with gaseous C6Cl6 generates carbon nanotubes (ca. 250 nm, wall thickness of 20 nm, tube length of 60 microm) inside the AAO channels. Highly aligned bundles of nearly amorphous carbon nanotubes are isolated after AAO is removed.

  14. Oxygen-Sodium Anticorrelation in Field RR Lyr-Type Stars

    NASA Astrophysics Data System (ADS)

    Andrievsky, S.; Korotin, S.; Lyashko, D.; Tsymbal, V.

    2017-06-01

    We have performed analysis of a large amount of the fields RR Lyr type stars spectra with the aim to derive NLTE oxygen and sodium abundances in our program stars. Fundamental parameters (Teff, log g, Vt) and metallicity were found using the method of the fitting between synthetic and observed spectra using the SME program which was developed by N. Piskunov and J. A. Valenti. As a result of this analysis anticorrelation between oxygen (O/H) and sodium (Na/H) abundances was found.

  15. Non-Equilibrium Green’s Function Study of Transport in Disordered Double-Layer Graphene Systems

    DTIC Science & Technology

    2011-01-01

    particles like electrons and holes. The Pauli exclusion principle prevents fermions from occupying the same quantum state, limiting the expectation...sity approximation. In Eq. 6.2, µ represents a vector that isolates each of the Cartesian components of the pairing vector, σµ represents the Pauli spin...devices on SiO2,” Nat. Nano, vol. 3, pp. 206–209, 2008. [35] X. Li, W. Cai, J. An, S. Kim, J. Nah, D. Yang, R. Piner, A. Velamakanni, I. Jung , E

  16. The genetic relationship between extirpated and contemporary Atlantic salmon Salmo salar L. lines from the southern Baltic Sea.

    PubMed

    Bernaś, Rafał; Poćwierz-Kotus, Anita; Dębowski, Piotr; Wenne, Roman

    2016-04-01

    The genetic relationship between original Atlantic salmon populations that are now extinct in the southern Baltic Sea and the present-day populations has long been controversial. To investigate and clarify this issue, we successfully genotyped individuals of the historical populations from the Oder and Vistula Rivers using DNA extracted from dried scales with the Atlantic salmon single nucleotide polymorphism array. Our results showed a global F ST of 0.2515 for all pairs of loci, which indicates a high level of genetic differentiation among the groups analyzed in this study. Pairwise F ST values were significant for all comparisons and the highest values were found between present-day reintroduced Slupia River salmon and extinct Vistula River Atlantic salmon. Bayesian analysis of genetic structure revealed the existence of substructures in the extirpated Polish populations and three main clades among studied stocks. The historical salmon population from the Oder River was genetically closer to present-day salmon from the Neman River than to the historical salmon from the Vistula River. Vistula salmon clearly separated from all other analyzed salmon stocks. It is likely that the origins of the Atlantic salmon population from the Morrum River and the Polish historical native populations are different.

  17. Experimental and Quantum Mechanics Investigations of Early Reactions of Monomethylhydrazine with Mixtures of NO2 and N2O4

    DTIC Science & Technology

    2013-02-15

    red fuming nitric acid (RFNA), which is composed of nitric acid (HNO3, 85 wt%) and NO2 (8–15 wt%). Recently the impinging stream vortex engine (ISVE... nitric acid [51]. As a result, growth of the particles is favored over H-abstraction reactions at the low temperatures of our experiments. As the...followed by the proton transfer from NAH bond to NO3 to form nitric acid , as shown in Scheme 3. Although it is very easy to form nitric acid (enthalpic

  18. Atmosphärisches Plasma in der Medizintechnik

    NASA Astrophysics Data System (ADS)

    Beer, Thomas; Knospe, Alexander; Buske, Christian

    Bei der Fertigung komplexer Bauteile werden immer häufiger unterschiedlichste Materialien zur Erfüllung der Funktion kombiniert. Kunststoff, Metall, Glas oder Keramik müssen miteinander verbunden werden. Dies gilt für die unterschiedlichsten Industriebereiche; von der Halbleiter-/Elektronikindustrie [1, 2] über die Automobilindustrie [3, 4] bis hin zur Medizintechnik werden für Verklebungs- [5], Bedruckungs-, Lackier- [6] und Anspritzprozesse optimal vorbehandelte Oberflächen benötigt.

  19. Sword or Ploughshare? New Roles for NATO and the Changing Nature of Transatlantic Relations

    DTIC Science & Technology

    2008-02-01

    2006. 47 Olaf Theiler, “Die NATO im Umbruch” [NATO in a State of Upheaval]; pp. 70 -76. 48 Robert Weaver, “NACC’s Five Years of Strengthening...defense policy.” Gustav E. Gustenau and Johann Frank, “Divergenz oder Komplementarität?” [Divergent or Complementary?], p. 13. 70 “Riga Summit...participation of British and also (with restrictions) French armed forces in Operation “Desert Storm” sent an important signal regarding the future

  20. Area Handbook Series: East Germany: A Country Study

    DTIC Science & Technology

    1987-07-01

    annexation of Schleswig- Holstein , then used Austria’s rejection as a pretext for war. The Seven Weeks’ War, which was won by Prus- sia, resulted in the...northern Schleswig- Holstein , and all overseas colonies; and the Allied Reparations Commission was established and charged with 24 Historical Setting...lands under foreign administration. However, the Mos- cow and Warsaw treaties, signed by West Germany in 1970, for- mally confirmed the Oder.-Neisse line

  1. Role of hydrogen sulfide within the dorsal motor nucleus of the vagus in the control of gastric function in rats.

    PubMed

    Sun, H-Z; Yu, K-H; Ai, H-B

    2015-05-01

    Hydrogen sulfide (H2 S) is a gaseous messenger and serves as an important neuromodulator in the central nervous system. This study aimed to clarify the role of H2 S within the dorsal motor nucleus of the vagus (DMV) in the control of gastric function in rats. Cystathionine β-synthetase (CBS) is an important generator of endogenous H2 S in the brain. We investigated the distribution of CBS in the DMV using immunohistochemical method, and the effects of H2 S on gastric motility and on gastric acid secretion. CBS-immunoreactive (IR) neurons were detected in the rostral, intermediate and caudal DMV, with the highest number of CBS-IR neurons in the caudal DMV, and the lowest in the intermediate DMV. We also found that microinjection of the exogenous H2 S donor NaHS (0.04 and 0.08 mol/L; 0.1 μL; n = 6; p < 0.05) into the DMV significantly inhibited gastric motility with a dose-dependent trend, and promoted gastric acid secretion in Wistar rats. Microinjection of the same volume of physiological saline (PS; 0.1 μL, n = 6, p > 0.05) at the same location did not noticeably change gastric motility and acid secretion. The data from these experiments suggest that the CBS that produces H2 S is present in the DMV, and microinjection of NaHS into the DMV inhibited gastric motility and enhanced gastric acid secretion in rats. © 2015 John Wiley & Sons Ltd.

  2. pH changes in frog rods upon manipulation of putative pH-regulating transport mechanisms.

    PubMed

    Kalamkarov, G; Pogozheva, I; Shevchenko, T; Koskelainen, A; Hemila, S; Donner, K

    1996-10-01

    Rod intracellular pH (pHi) in the intact frog retina was measured fluorometrically with the dye 2',7'-bis(2-carboxyethyl)-5(and-6)-carboxyfluorescein under treatments chosen to affect putative pH-regulating transport mechanisms in the plasma membrane. The purpose was to relate possible pHi changes to previously reported effects on photoresponses. In nominally bicarbonate-free Ringer, application of amiloride (1 mM) or substitution of 95 mM external Na+ by K+ or choline triggered monotonic but reversible acidifications, consistent with inhibition of Na+/H+ exchange. Bicarbonate-dependent mechanisms were characterized as follows: (1) Replacing half of a 12 mM phosphate buffer by bicarbonate caused a sustained rise of pHi. (2) Subsequent application of the anion transport inhibitor 4,4'-diisothiocyanatostilbene-2',2'-disulphonic acid (DIDS, 0.2 mM) set off a slow acidification. (3) Substitution of external Cl- by gluconate (95 mM) caused a rapid pHi rise both in normal Na+ and low-Na+ perfusion. (4) This effect was inhibited by DIDS. The results support a consistent explanation of parallel electrophysiological experiments on the assumption that intracellular acidifications reduce and alkalinizations (in a certain range) augment photoresponses. It is concluded that both Na+/H+ exchange and bicarbonate transport control rod pHi, modulating the light-sensitive current. Part of the bicarbonate transport is by Na(+)-independent HCO3-/Cl- exchange, but a further Na(+)-coupled bicarbonate import mechanism is implicated.

  3. Co-overexpressing a Plasma Membrane and a Vacuolar Membrane Sodium/Proton Antiporter Significantly Improves Salt Tolerance in Transgenic Arabidopsis Plants.

    PubMed

    Pehlivan, Necla; Sun, Li; Jarrett, Philip; Yang, Xiaojie; Mishra, Neelam; Chen, Lin; Kadioglu, Asim; Shen, Guoxin; Zhang, Hong

    2016-05-01

    The Arabidopsis gene AtNHX1 encodes a vacuolar membrane-bound sodium/proton (Na(+)/H(+)) antiporter that transports Na(+) into the vacuole and exports H(+) into the cytoplasm. The Arabidopsis gene SOS1 encodes a plasma membrane-bound Na(+)/H(+) antiporter that exports Na(+) to the extracellular space and imports H(+) into the plant cell. Plants rely on these enzymes either to keep Na(+) out of the cell or to sequester Na(+) into vacuoles to avoid the toxic level of Na(+) in the cytoplasm. Overexpression of AtNHX1 or SOS1 could improve salt tolerance in transgenic plants, but the improved salt tolerance is limited. NaCl at concentration >200 mM would kill AtNHX1-overexpressing or SOS1-overexpressing plants. Here it is shown that co-overexpressing AtNHX1 and SOS1 could further improve salt tolerance in transgenic Arabidopsis plants, making transgenic Arabidopsis able to tolerate up to 250 mM NaCl treatment. Furthermore, co-overexpression of AtNHX1 and SOS1 could significantly reduce yield loss caused by the combined stresses of heat and salt, confirming the hypothesis that stacked overexpression of two genes could substantially improve tolerance against multiple stresses. This research serves as a proof of concept for improving salt tolerance in other plants including crops. © The Author 2016. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists.

  4. Methylmercury-induced inhibition of regulatory volume decrease in astrocytes: characterization of osmoregulator efflux and its reversal by amiloride.

    PubMed

    Aschner, M; Vitarella, D; Allen, J W; Conklin, D R; Cowan, K S

    1998-11-16

    Swelling of neonatal rat primary astrocyte cultures by hypotonic media leads to regulatory volume decrease (RVD) and the resumption of resting cell volume. RVD is associated with activation of conductive K+ and Cl- channels, allowing for the escape of KCl, as well as the release of osmoregulators, such as taurine and myoinositol. As we have previously shown [D. Vitarella, H.K. Kimelberg, M. Aschner, Inhibition of RVD in swollen rat primary astrocyte cultures by methylmercury (MeHg) is due to increase amiloride-sensitive Na+ uptake, Brain Res. 732 (1996) 169-178.], MeHg, when added to hypotonic buffer inhibits RVD, primarily due to increased cellular permeability to Na+ via the Na+/H+ antiporter. The present study was, therefore, undertaken to assess the ability of cation-anion cotransport blockers to reverse the inhibitory effect of MeHg on RVD in swollen astrocytes, and to further characterize MeHg-induced changes in astrocytic osmoregulatory release processes. The studies demonstrate the following: (1) MeHg-induced inhibition of RVD is partially inhibited by the Na+/H+ antiporter blocker, amiloride, but not SITS (4-acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic acid), DIDS (4,4'-diisothiocyano-2,2'-stilbenedisulfonic acid), furosemide or bumetanide; (2) exposure of swollen astrocytes to MeHg is associated with specific effects on osmoregulatory release, leading to significant inhibition of taurine release and a significant increase in potassium and myoinositol release compared with release in hypotonic conditions. Copyright 1998 Elsevier Science B.V.

  5. Sound field separation with sound pressure and particle velocity measurements.

    PubMed

    Fernandez-Grande, Efren; Jacobsen, Finn; Leclère, Quentin

    2012-12-01

    In conventional near-field acoustic holography (NAH) it is not possible to distinguish between sound from the two sides of the array, thus, it is a requirement that all the sources are confined to only one side and radiate into a free field. When this requirement cannot be fulfilled, sound field separation techniques make it possible to distinguish between outgoing and incoming waves from the two sides, and thus NAH can be applied. In this paper, a separation method based on the measurement of the particle velocity in two layers and another method based on the measurement of the pressure and the velocity in a single layer are proposed. The two methods use an equivalent source formulation with separate transfer matrices for the outgoing and incoming waves, so that the sound from the two sides of the array can be modeled independently. A weighting scheme is proposed to account for the distance between the equivalent sources and measurement surfaces and for the difference in magnitude between pressure and velocity. Experimental and numerical studies have been conducted to examine the methods. The double layer velocity method seems to be more robust to noise and flanking sound than the combined pressure-velocity method, although it requires an additional measurement surface. On the whole, the separation methods can be useful when the disturbance of the incoming field is significant. Otherwise the direct reconstruction is more accurate and straightforward.

  6. The NHERF1 PDZ2 Domain Regulates PKA–RhoA–p38-mediated NHE1 Activation and Invasion in Breast Tumor Cells

    PubMed Central

    Cardone, Rosa A.; Bellizzi, Antonia; Busco, Giovanni; Weinman, Edward J.; Dell'Aquila, Maria E.; Casavola, Valeria; Azzariti, Amalia; Mangia, Anita; Paradiso, Angelo

    2007-01-01

    Understanding the signal transduction systems governing invasion is fundamental for the design of therapeutic strategies against metastasis. Na+/H+ exchanger regulatory factor (NHERF1) is a postsynaptic density 95/disc-large/zona occludens (PDZ) domain-containing protein that recruits membrane receptors/transporters and cytoplasmic signaling proteins into functional complexes. NHERF1 expression is altered in breast cancer, but its effective role in mammary carcinogenesis remains undefined. We report here that NHERF1 overexpression in human breast tumor biopsies is associated with metastatic progression, poor prognosis, and hypoxia-inducible factor-1α expression. In cultured tumor cells, hypoxia and serum deprivation increase NHERF1 expression, promote the formation of leading-edge pseudopodia, and redistribute NHERF1 to these pseudopodia. This pseudopodial localization of NHERF1 was verified in breast biopsies and in three-dimensional Matrigel culture. Furthermore, serum deprivation and hypoxia stimulate the Na+/H+ exchanger, invasion, and activate a protein kinase A (PKA)-gated RhoA/p38 invasion signal module. Significantly, NHERF1 overexpression was sufficient to induce these morphological and functional changes, and it potentiated their induction by serum deprivation. Functional experiments with truncated and binding groove-mutated PDZ domain constructs demonstrated that NHERF1 regulates these processes through its PDZ2 domain. We conclude that NHERF1 overexpression enhances the invasive phenotype in breast cancer cells, both alone and in synergy with exposure to the tumor microenvironment, via the coordination of PKA-gated RhoA/p38 signaling. PMID:17332506

  7. Tumor suppressor gene adenomatous polyposis coli downregulates intestinal transport.

    PubMed

    Rexhepaj, Rexhep; Rotte, Anand; Gu, Shuchen; Michael, Diana; Pasham, Venkanna; Wang, Kan; Kempe, Daniela S; Ackermann, Teresa F; Brücher, Björn; Fend, Falko; Föller, Michael; Lang, Florian

    2011-05-01

    Loss of function mutations of the tumor suppressor gene adenomatous polyposis coli (APC) underly the familial adenomatous polyposis. Mice carrying an inactivating mutation in the apc gene (apc (Min/+)) similarly develop intestinal polyposis. APC is effective at least in part by degrading β-catenin and lack of APC leads to markedly enhanced cellular β-catenin levels. β-Catenin has most recently been shown to upregulate the Na+/K+ ATPase. The present study, thus, explored the possibility that APC could influence intestinal transport. The abundance and localization of β-catenin were determined utilizing Western blotting and confocal microscopy, the activity of the electrogenic glucose carrier (SGLT1) was estimated from the glucose-induced current in jejunal segments utilizing Ussing chamber experiments and the Na+/H+ exchanger (NHE3) activity from Na+ -dependent re-alkalinization of cytosolic pH (ΔpH(i)) following an ammonium pulse employing BCECF fluorescence. As a result, β-catenin abundance in intestinal tissue was significantly higher in apc (Min/+) mice than in wild-type mice (apc (+/+)). The β-catenin protein was localized in the basolateral membrane. Both, the glucose-induced current and ΔpH(i) were significantly higher in apc (Min/+) mice than in apc (+/+) mice. In conclusion, intestinal electrogenic transport of glucose and intestinal Na+/H+ exchanger activity are both significantly enhanced in apc (Min/+) mice, pointing to a role of APC in the regulation of epithelial transport.

  8. Antimicrobial properties and dentin bonding strength of magnesium phosphate cements.

    PubMed

    Mestres, G; Abdolhosseini, M; Bowles, W; Huang, S-H; Aparicio, C; Gorr, S-U; Ginebra, M-P

    2013-09-01

    The main objective of this work was to assess the antimicrobial properties and the dentin-bonding strength of novel magnesium phosphate cements (MPC). Three formulations of MPC, consisting of magnesium oxide and a phosphate salt, NH4H2PO4, NaH2PO4 or a mixture of both, were evaluated. As a result of the setting reaction, MPC transformed into either struvite (MgNH4PO4·6H2O) when NH4H2PO4 was used or an amorphous magnesium sodium phosphate when NaH2PO4 was used. The MPC had appropriate setting times for hard tissue applications, high early compressive strengths and higher strength of bonding to dentin than commercial mineral trioxide aggregate cement. Bacteriological studies were performed with fresh and aged cements against three bacterial strains, Escherichia coli, Pseudomonas aeruginosa (planktonic and in biofilm) and Aggregatibacter actinomycetemcomitans. These bacteria have been associated with infected implants, as well as other frequent hard tissue related infections. Extracts of different compositions of MPC had bactericidal or bacteriostatic properties against the three bacterial strains tested. This was associated mainly with a synergistic effect between the high osmolarity and alkaline pH of the MPC. These intrinsic antimicrobial properties make MPC preferential candidates for applications in dentistry, such as root fillers, pulp capping agents and cavity liners. Copyright © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  9. Medium-term and long-term outcomes of interventions for primary psoas tendinopathy.

    PubMed

    Garala, Kanai; Prasad, Vishnu; Jeyapalan, Kanagaratnam; Power, Richard A

    2014-05-01

    To assess medium- and long-term outcomes of psoas tendinopathy to psoas tenotomy and image-guided steroid injections. This is a 14-year retrospective case-control study to identify the efficacy of psoas tenotomy and image-guided steroid injections. This study was undertaken in a secondary care setting. Patients with confirmed psoas tendinopathy were followed up by postal questionnaire, which included a nonarthritic hip score (NAHS) and a study patient satisfaction questionnaire. Patients underwent image-guided steroid injections. Depending on the analgesic or symptomatic relief, some patients proceeded to psoas tenotomy. Response to steroid injection. Pain relief and symptomatic relief after the surgery. Twenty-three patients were reviewed with a 70% follow-up over a time of 49 months for surgery (range, 13-144 months) and 77 months for injection (range, 14-160 months). Eight patients had a lasting response to injection and required no further intervention, and 15 patients proceeded to psoas tenotomy using a medial Ludloff approach. The average NAHS scores after the surgery and injection were 66.15 and 76.08, respectively. Ten patients reported pain relief after their tenotomy, and 5 patients reported no change in pain. All 8 patients, who only underwent injection, reported lasting pain relief. Local steroid injections can provide long-term relief for patients presenting with psoas tendinopathy. For those patients with only temporary relief from injection, psoas tenotomy can provide good long-term pain relief.

  10. Intrinsic Cholinergic Mechanisms Regulating Cerebral Blood Flow as a Target for Organophosphate Action.

    DTIC Science & Technology

    1985-10-01

    regions one hour 26 following microinjection of YH- choline into the right parietal cortex. II Effect of atropine sulfate (0.3 mg/kg i.v.) on the...Harvard Apparatus model 940). The superfusate consisted of a modified Kreb’s- bicarbonate buffer containing physostigmine to inhibit ACh degradation...in mM: NaCl, 118; CaCI 2 , 1.2; KC01, 4.8; MgSO4, 1.2; NaH 2 PO 4 , 1.2; NaHCO 3 , 25; choline chloride, 0.001; physostigmine, 0.1). The area of the

  11. The latest development of antihypertensive medication

    NASA Astrophysics Data System (ADS)

    Nasution, S.; Rey, I.; Effendi-YS, R.

    2018-03-01

    Hypertension is the most common risk factor for cardiovascular disease, stroke, renal failure, and death. Recent drug monitoring studies found non-adherence to BP lowering therapy in 25% to 65% of patients with apparent treatment-resistant hypertension (TRH). This review focuses on the latest development of antihypertensive medication, such as vasopeptidase inhibitors, aldosterone synthase inhibitors, Soluble Epoxide Hydrolase Inhibitors, agonists of natriuretic peptide receptor, Vasoactive Intestinal Peptide Receptor Agonist, a novel mineralocorticoid receptor antagonist, inhibitors of aminopeptidase A, dopamine β-hydroxylase inhibitor, intestinal Na+/H+ exchanger 3 inhibitor and other agents.

  12. Soviet Naval Military and Air Power in the Third World,

    DTIC Science & Technology

    1984-03-31

    enhanced by the impressive Kirov class nucler - powered , guided missile cruiser. This ship is the largest naval vessel built byanynation since World ’W...RD-Rli5e 290 SOVIET NAVAL MILITARY AND AIR POWER IN THE THIRD WORLD i/I (U) KENT STATE UNIV OH LYMAN L LEMNITZER CENTER FOR NATO STUDIES L J ANDOLINO...ii . MICROCOPY RESOLUTION TEST CHART NAh{ThAL BUPIAU OF STANDAR[)S 4 -.1 21 -.!r z r o SOVIET NAVAL MILITARY AND AIR 0’) POWER IN THE THIRD WORLD o by

  13. Study of the Surface Morphology of Thermally Annealed Copper Foils and Various Transfer Methods for Graphene

    DTIC Science & Technology

    2013-01-01

    suggesting the doping effect which owes to the Pauli Exclusion Principle for electrons and holes where the phonon cannot decay into electron-hole pairs...2011, 11, 3519−3525. [7] Li, X. S.; Cai, W. W.; An, J. H.; Kim, S.; Nah, J.; Yang, D. X.; Piner, R. D.; Velamakanni, A.; Jung , I.; Tutuc, E.; et al...Wu, W.; Yu, O.; Yitamben, E. N.; Fisher, B.; Guest, J. R.; Chen, Y. P.; et al. ACS Nano 2011, 5, 3607−3613. [24] Li, X. S.; Cai, W. W.; Jung , I. H

  14. Clausewitz’s Center of Gravity: It’s Not What We Thought

    DTIC Science & Technology

    2003-01-01

    planning process is con- trived and unnecessary. In the Gulf War (1990–91), for example—a limited conflict in which, according to Clausewitz, the CoG...constructive purpose. The Gulf War of 1990–91 was not. The industrial-age paradigm of warfare, in which the distinction between the strategic, operational, and...Kriegführenden, sei es ein einzelner Staat oder ein Bündnis von Staaten, haben eine gewisse Einheit und durch diese Zusammenhang; wo aber Zusammenhang ist

  15. Clausewitz’s Center of Gravity: Changing Our Warfighting Doctrine-Again!

    DTIC Science & Technology

    2002-09-01

    collapse of the enemy—tend to compete with the typically more restricted political objective(s). For example, during the Gulf War the ground component...under Clausewitz’s concept, determining the Iraqi CoG would have been unnecessary since the Gulf War was not a war of annihilation. Simply translating the...Schwerpunkt der Kraft erhalten wird, so ist es auch im Kriege. Die Streitkräfte jedes Kriegführenden, sei es ein einzelner Staat oder ein Bündnis von

  16. A Sixty-Year Timeline of the Air Force Maui Optical and Supercomputing Site

    DTIC Science & Technology

    2013-01-01

    19.3 million dollar contract to Contraves USA to build the AEOS 3.67-m telescope. Site Management Duffner, 2009 May 1992 The Air Force approves...system. Site Management Oder, undated Dec 18 1996 Contraves completes factory testing of AEOS telescope at its plant in Pennsylvania...States. Dec 13 1991 The Air Force awards a $19.3 million dollar contract to Contraves USA to build the AEOS 3.67-m telescope. May 1992 The Air Force

  17. Von Donuts und Zucker: Mit Neutronen biologische Makromoleküle erforschen

    NASA Astrophysics Data System (ADS)

    May, Roland P.

    2003-05-01

    Für die Erforschung von Biomolekülen bieten Neutronen einzigartige Eigenschaften. Vor allem ihre unterschiedliche Wechselwirkung mit dem natürlichen Wasserstoff und seinem schweren Isotop Deuterium ermöglicht tiefe Einblicke in Struktur, Funktion und Dynamik von Proteinen, Nukleinsäuren und Biomembranen. Bei vielen Fragestellungen zur Strukturaufklärung gibt es kaum oder keine Alternative zum Neutron. Das Institut Laue-Langevin trägt Bahnbrechendes zum Erfolg der Neutronen-Methoden in der Biologie bei.

  18. [Drug-Coated Balloons and Stents for the Treatment of Femoro-Popliteal Lesions].

    PubMed

    Ito, Wulf D

    2017-08-01

    Medikamenten-beschichtete Ballons bei femoro-poplitealen Läsionen  Medikamenten-beschichtete Ballons (DCB) führen in der Behandlung von femoro-poplitealen Läsionen zu besseren Offenheitsraten als die einfache Ballondilatation und zu ähnlichen bis besseren Offenheitsraten als die Stentimplantation. Vorteil ist die Vermeidung von permanentem Fremdmaterial in Regionen, die einer ständigen mechanischen Beanspruchung unterworfen sind und die Möglichkeit, die Prozedur an derselben Stelle wiederholen zu können bzw. chirurgische Zugangswege offenzuhalten. Bei Auftreten von Dissektionen oder einem Recoil bietet sich die fokale Implantation möglichst kurzer Stents in den betroffenen Segmenten an. Die primäre Implantation Medikamenten-beschichteter Stents zeigt darüber hinaus keinen weiteren Vorteil und ist auf längere Sicht mit den Nachteilen der Implantation von Fremdmaterial in Bewegungssegmenten behaftet. Nicht medikamentöse und medikamentöse Begleittherapie  Die Kombination aus interventioneller Behandlung und supervidiertem Gehtraining zeigt die besten Erfolgsaussichten einer dauerhaften Verbesserung der Gehstrecke bei Patienten mit femoro-poplitealen Läsionen und ist einer alleinigen interventionellen Behandlung oder einem alleinigen Gehtraining überlegen. Darüber hinaus werden aktuell große randomisierte, kontrollierte Studien durchgeführt, die den Einfluss niedrig dosierter direkter Antikoagulanzien auf die kardiovaskuläre Komplikationsrate nach Intervention untersuchen. Die Ergebnisse dieser Studien werden Aufschluss geben über die optimale antithrombotische Therapie nach Intervention im femoro-poplitealen Stromgebiet.

  19. Lipomatosen.

    PubMed

    Al Ghazal, Philipp; Grönemeyer, Lisa-Lena; Schön, Michael P

    2018-03-01

    Als Lipomatosen bezeichnet man gutartige, meist ohne eindeutige Auslöser auftretende Vermehrungen des Fettgewebes, oft mit typischem Verteilungsmuster. Im Gegensatz zu umschriebenen Lipomen entwickeln sie sich meist diffus-symmetrisch und sind nicht von einer fibrösen Pseudokapsel umgeben. Am häufigsten ist die benigne symmetrische Lipomatose (BSL; Launois-Bensaude-Syndrom), von der aufgrund des Verteilungsmusters des hyperplastischen Fettgewebes vier Typen unterschieden werden. Ätiologie und Pathogenese der Erkrankung sind noch weitgehend unbekannt, wobei manche Formen eine hereditäre Basis zu haben oder mit vermehrtem Alkoholkonsum assoziiert zu sein scheinen. In einigen Fällen wurden mitochondriale Fehlfunktionen nachgewiesen. Lipomatosen können isoliert, aber auch mit Begleitsymptomen oder -erkrankungen (Komorbidität) vergesellschaftet auftreten. Wirksame medikamentöse Therapien sind nicht bekannt; chirurgische Verfahren können hingegen zur Besserung der Symptome führen. Die von der BSL abzugrenzende Lipomatosis dolorosa tritt bevorzugt bei Frauen mittleren Alters auf und ist durch Vermehrung des Fettgewebes sowie starke Schmerzen in den betroffenen Bereichen gekennzeichnet. Verschiedene Differenzialdiagnosen und Begleiterkrankungen sind abzuklären, insbesondere Depressionen. Evidenzbasierte Therapieempfehlungen existieren nicht. Repetitive Lidocain-Infusionen können temporäre Besserungen bewirken; nach chirurgischen Interventionen treten häufig Rezidive auf, allerdings werden auch langfristige Erfolge erzielt. © 2018 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

  20. Weiße und Braune Zwerge zeigen sich unwirtlich

    NASA Astrophysics Data System (ADS)

    Heller, René

    2013-02-01

    Mehr als 850 Exoplaneten haben Astronomen seit dem Jahr 1992 nachgewiesen. Die meisten von ihnen umkreisen normale Hauptreihensterne, aber es wurden auch Trabanten im Umlauf um Braune oder Weiße Zwerge aufgespürt. Nun haben Rory Barnes von der University of Washington in Seattle und René Heller am Leibniz-Institut für Astrophysik Potsdam die Bewohnbarkeit möglicher Planeten um solche Objekte untersucht und dabei festgestellt, dass sie für Leben, wie wir es kennen, ungeeignet sind.

  1. Aeroelasticity, Aerothermoelasticity and Aeroelastic Scaling of Hypersonic Vehicles

    DTIC Science & Technology

    2004-12-01

    P. Friedmann Frangois-Xavier Bagnoud Professor Phone 734-763-2354; FAX 734-763-0578; Email peretzf@umich.edu Co-Principal Investigator: Kenneth G...34 order pimon theory - -- -- - C - uter. corne ! - -- v - -- tiner. refined80000 ’Z-". n .,- l- 70000 70000 6 110000 30000 F 20000 10000 2.5 5 7,5 10 12.5...hypersonic vehicle, calculated using 3rd order piston theory and Euler aerodynamics -- 3"• V o-der pistom theory . - ---- Euk-r, col-sc - -- 7

  2. Inorganic carbon fixation by chemosynthetic ectosymbionts and nutritional transfers to the hydrothermal vent host-shrimp Rimicaris exoculata

    PubMed Central

    Ponsard, Julie; Cambon-Bonavita, Marie-Anne; Zbinden, Magali; Lepoint, Gilles; Joassin, André; Corbari, Laure; Shillito, Bruce; Durand, Lucile; Cueff-Gauchard, Valérie; Compère, Philippe

    2013-01-01

    The shrimp Rimicaris exoculata dominates several hydrothermal vent ecosystems of the Mid-Atlantic Ridge and is thought to be a primary consumer harbouring a chemoautotrophic bacterial community in its gill chamber. The aim of the present study was to test current hypotheses concerning the epibiont's chemoautotrophy, and the mutualistic character of this association. In-vivo experiments were carried out in a pressurised aquarium with isotope-labelled inorganic carbon (NaH13CO3 and NaH14CO3) in the presence of two different electron donors (Na2S2O3 and Fe2+) and with radiolabelled organic compounds (14C-acetate and 3H-lysine) chosen as potential bacterial substrates and/or metabolic by-products in experiments mimicking transfer of small biomolecules from epibionts to host. The bacterial epibionts were found to assimilate inorganic carbon by chemoautotrophy, but many of them (thick filaments of epsilonproteobacteria) appeared versatile and able to switch between electron donors, including organic compounds (heterotrophic acetate and lysine uptake). At least some of them (thin filamentous gammaproteobacteria) also seem capable of internal energy storage that could supply chemosynthetic metabolism for hours under conditions of electron donor deprivation. As direct nutritional transfer from bacteria to host was detected, the association appears as true mutualism. Import of soluble bacterial products occurs by permeation across the gill chamber integument, rather than via the digestive tract. This first demonstration of such capabilities in a decapod crustacean supports the previously discarded hypothesis of transtegumental absorption of dissolved organic matter or carbon as a common nutritional pathway. PMID:22914596

  3. Intracellular pH change does not accompany egg activation in the mouse.

    PubMed

    Phillips, K P; Baltz, J M

    1996-09-01

    In the sea urchin, some other marine invertebrates, and the frog, Xenopus, egg activation at fertilization is accompanied by an increase in intracellular pH (pHi). We measured pHi in germinal vesicle (GV)-intact mouse oocytes, ovulated eggs, and in vivo fertilized zygotes using the pH indicator dye, SNARF-1. The mean pH, was 6.96 +/- 0.004 (+/- SEM) in GV-intact oocytes, 7.00 +/- 0.01 in ovulated, unfertilized eggs, and 7.02 +/- 0.01 in fertilized zygotes, indicating no sustained changes in pHi after germinal vesicle breakdown (GVBD) or fertilization. To examine whether transient changes in pHi occur shortly after egg activation, mouse eggs were parthenogenetically activated by 7% ethanol in phosphate buffered saline (PBS); no significant change in pHi followed ethanol activation. Since increased Na+/H+ antiporter activity is responsible for pHi increase in the sea urchin, pHi was measured in the absence of added bicarbonate or CO2 (a condition under which the antiporter would be the only major pHi regulatory mechanism able to operate, since the others were bicarbonate-dependent) in GV-intact oocytes, ovulated eggs, and in vivo fertilized zygotes to determine whether a Na+/H+ antiporter was activated. There was no physiologically significant difference in pHi after GVBD or fertilization, when pHi was measured in bicarbonate-free medium, nor any change upon parthenogenetic activation. Thus, a change in pHi is not a feature of egg activation in the mouse.

  4. Synthesis, Biological Evaluation and Molecular Docking of New Benzenesulfonylhydrazone as Potential anti-Trypanosoma cruzi Agents.

    PubMed

    Elizondo-Jimenez, Silvia; Moreno-Herrera, Antonio; Reyes-Olivares, Rogelio; Dorantes-Gonzalez, Edith; Nogueda-Torres, Benjamín; Oliveira, Eduardo A Gamosa de; Romeiro, Nelilma C; Lima, Lidia M; Palos, Isidro; Rivera, Gildardo

    2017-01-01

    Chagas disease is a public health problem caused by Trypanosoma cruzi. Cruzain is a pharmacological target for designing a new drug against this parasite. Hydrazone and Nacylhydrazone derivatives have been traditionally associated as potential Cruzain inhibitors. Additionally, benzenesulfonyl derivatives show trypanocidal activity. Therefore, in this study, the combination of both structures has been taken into account for drug design. Seven benzenesulfonylhydrazone (BS-H) and seven N-propionyl benzenesulfonylhydrazone (BS-NAH) derivatives were synthetized and elucidated by infrared spectroscopy, nuclear magnetic resonance, and elemental analysis. All compounds were evaluated biologically in vitro against two strains of Trypanosoma cruzi (NINOA and INC-5), which are endemic in Mexico, and compared with the reference drugs nifurtimox and benznidazole. In order to gain insight into the putative molecular origin of the trypanocidal properties of these derivatives, docking studies were carried out with Cruzain. Compounds 4 and 6 (BS-H) and 10, 12-14 (BS-NAH) showed the best biological activity against NINOA and INC-5 strains, respectively. Compound 13 was the most potent trypanocidal compound showing a LC50 of 0.06 µM against INC-5 strain. However, compound 4 showed the best activity against both strains (LC50 <30 µM). Theoretical binding modes obtained suggested covalent binding that could explain their biological activity. Benzenesulfonyl and N-propionyl benzenesulfonyl hydrazone derivatives are good options for developing new trypanocidal agents. Particularly, compound 4 could be considered a lead compound. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  5. Critical role for NHE1 in intracellular pH regulation in pancreatic acinar cells.

    PubMed

    Brown, David A; Melvin, James E; Yule, David I

    2003-11-01

    The primary function of pancreatic acinar cells is to secrete digestive enzymes together with a NaCl-rich primary fluid which is later greatly supplemented and modified by the pancreatic duct. A Na+/H+ exchanger(s) [NHE(s)] is proposed to be integral in the process of fluid secretion both in terms of the transcellular flux of Na+ and intracellular pH (pHi) regulation. Multiple NHE isoforms have been identified in pancreatic tissue, but little is known about their individual functions in acinar cells. The Na+/H+ exchange inhibitor 5-(N-ethyl-N-isopropyl) amiloride completely blocked pHi recovery after an NH4Cl-induced acid challenge, confirming a general role for NHE in pHi regulation. The targeted disruption of the Nhe1 gene also completely abolished pHi recovery from an acid load in pancreatic acini in both HCO3--containing and HCO3--free solutions. In contrast, the disruption of either Nhe2 or Nhe3 had no effect on pHi recovery. In addition, NHE1 activity was upregulated in response to muscarinic stimulation in wild-type mice but not in NHE1-deficient mice. Fluctuations in pHi could potentially have major effects on Ca2+ signaling following secretagogue stimulation; however, the targeted disruption of Nhe1 was found to have no significant effect on intracellular Ca2+ homeostasis. These data demonstrate that NHE1 is the major regulator of pHi in both resting and muscarinic agonist-stimulated pancreatic acinar cells.

  6. Influence of phosphorous fertilization on copper phytoextraction and antioxidant defenses in castor bean (Ricinus communis L.).

    PubMed

    Huang, Guoyong; Rizwan, Muhammad Shahid; Ren, Chao; Guo, Guangguang; Fu, Qingling; Zhu, Jun; Hu, Hongqing

    2018-01-01

    Application of fertilizers to supply appropriate nutrients has become an essential agricultural strategy for enhancing the efficiency of phytoremediation in heavy metal contaminated soils. The present study was conducted to investigate the beneficial effects of three types of phosphate fertilizers (i.e., oxalic acid-activated phosphate rock (APR), Ca(H 2 PO 4 ) 2 , and NaH 2 PO 4 ) in the range of 0-600 mg P kg -1 soil, on castor bean growth, antioxidants [antioxidative enzymes and glutathione (GSH)], and Cu uptake. Results showed that with the addition of phosphorus fertilizers, the dry weight of castor bean and the Cu concentration in roots increased significantly, resulting in increased Cu extraction. The phosphorus concentration in both shoots and roots was increased as compared with the control, and the Ca(H 2 PO 4 ) 2 treatment had the greatest effect. Application of APR, NaH 2 PO 4 , and Ca(H 2 PO 4 ) 2 reduced the malondialdehyde (MDA) content, and the activity of the two antioxidant enzymes superoxide dismustase (SOD, EC 1.15.1.1) and catalase (CAT, EC 1.11.1.6) in the leaves of castor bean. GSH concentration in leaves increased with the increasing levels of phosphorus applied to soil as well as the accumulation of phosphorus in shoots, compared to the control. These results demonstrated that the addition of phosphorus fertilizers can enhance the resistance of castor bean to Cu and increase the Cu extraction efficiency of the plant from contaminated soils.

  7. Salt stress in Thellungiella halophila activates Na+ transport mechanisms required for salinity tolerance.

    PubMed

    Vera-Estrella, Rosario; Barkla, Bronwyn J; García-Ramírez, Liliana; Pantoja, Omar

    2005-11-01

    Salinity is considered one of the major limiting factors for plant growth and agricultural productivity. We are using salt cress (Thellungiella halophila) to identify biochemical mechanisms that enable plants to grow in saline conditions. Under salt stress, the major site of Na+ accumulation occurred in old leaves, followed by young leaves and taproots, with the least accumulation occurring in lateral roots. Salt treatment increased both the H+ transport and hydrolytic activity of salt cress tonoplast (TP) and plasma membrane (PM) H(+)-ATPases from leaves and roots. TP Na(+)/H+ exchange was greatly stimulated by growth of the plants in NaCl, both in leaves and roots. Expression of the PM H(+)-ATPase isoform AHA3, the Na+ transporter HKT1, and the Na(+)/H+ exchanger SOS1 were examined in PMs isolated from control and salt-treated salt cress roots and leaves. An increased expression of SOS1, but no changes in levels of AHA3 and HKT1, was observed. NHX1 was only detected in PM fractions of roots, and a salt-induced increase in protein expression was observed. Analysis of the levels of expression of vacuolar H(+)-translocating ATPase subunits showed no major changes in protein expression of subunits VHA-A or VHA-B with salt treatment; however, VHA-E showed an increased expression in leaf tissue, but not in roots, when the plants were treated with NaCl. Salt cress plants were able to distribute and store Na+ by a very strict control of ion movement across both the TP and PM.

  8. Salt Stress in Thellungiella halophila Activates Na+ Transport Mechanisms Required for Salinity Tolerance1

    PubMed Central

    Vera-Estrella, Rosario; Barkla, Bronwyn J.; García-Ramírez, Liliana; Pantoja, Omar

    2005-01-01

    Salinity is considered one of the major limiting factors for plant growth and agricultural productivity. We are using salt cress (Thellungiella halophila) to identify biochemical mechanisms that enable plants to grow in saline conditions. Under salt stress, the major site of Na+ accumulation occurred in old leaves, followed by young leaves and taproots, with the least accumulation occurring in lateral roots. Salt treatment increased both the H+ transport and hydrolytic activity of salt cress tonoplast (TP) and plasma membrane (PM) H+-ATPases from leaves and roots. TP Na+/H+ exchange was greatly stimulated by growth of the plants in NaCl, both in leaves and roots. Expression of the PM H+-ATPase isoform AHA3, the Na+ transporter HKT1, and the Na+/H+ exchanger SOS1 were examined in PMs isolated from control and salt-treated salt cress roots and leaves. An increased expression of SOS1, but no changes in levels of AHA3 and HKT1, was observed. NHX1 was only detected in PM fractions of roots, and a salt-induced increase in protein expression was observed. Analysis of the levels of expression of vacuolar H+-translocating ATPase subunits showed no major changes in protein expression of subunits VHA-A or VHA-B with salt treatment; however, VHA-E showed an increased expression in leaf tissue, but not in roots, when the plants were treated with NaCl. Salt cress plants were able to distribute and store Na+ by a very strict control of ion movement across both the TP and PM. PMID:16244148

  9. Exogenous hydrogen sulfide promotes cell proliferation and differentiation by modulating autophagy in human keratinocytes

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Xie, Xin; Dai, Hui; Zhuang, Binyu

    The effects and the underlying mechanisms of hydrogen sulfide (H{sub 2}S) on keratinocyte proliferation and differentiation are still less known. In the current study, we investigated the effects and the underlying mechanisms of exogenous H{sub 2}S on keratinocyte proliferation and differentiation. Human keratinocytes (HaCaT cells) were treated with various concentrations (0.05, 0.25, 0.5 and 1 mM) of sodium hydrosulfide (NaHS, a donor of H{sub 2}S) for 24 h. A CCK-8 assay was used to assess cell viability. Western blot analysis was performed to determine the expression levels of proteins associated with differentiation and autophagy. Transmission electron microscopy was performed to observe autophagicmore » vacuoles, and flow cytometry was applied to evaluate apoptosis. NaHS promoted the viability, induced the differentiation, and enhanced autophagic activity in a dose-dependent manner in HaCaT cells but had no effect on cell apoptosis. Blockage of autophagy by ATG5 siRNA inhibited NaHS-induced cell proliferation and differentiation. The current study demonstrated that autophagy in response to exogenous H{sub 2}S treatment promoted keratinocyte proliferation and differentiation. Our results provide additional insights into the potential role of autophagy in keratinocyte proliferation and differentiation. - Highlights: • Exogenous H{sub 2}S promotes keratinocyte proliferation and differentiation. • The effects of H{sub 2}S on proliferation and differentiation is modulated by autophagy. • Exogenous H{sub 2}S has no effect on keratinocyte apoptosis.« less

  10. Osmotic tolerance of avian spermatozoa: Influence of time, temperature, cryoprotectant and membrane ion pump function on sperm viability

    USGS Publications Warehouse

    Blanco, J.M.; Long, J.A.; Gee, G.; Donoghue, A.M.; Wildt, D.E.

    2008-01-01

    Potential factors influencing sperm survival under hypertonic conditions were evaluated in the Sandhill crane (Grus canadensis) and turkey (Meleagridis gallopavo). Sperm osmotolerance (300-3000 mOsm/kg) was evaluated after: (1) equilibration times of 2, 10, 45 and 60 min at 4 ?C versus 21 ?C; (2) pre-equilibrating with dimethylacetamide (DMA) or dimethylsulfoxide (Me2SO) at either 4 ?C or 21 ?C; and (3) inhibition of the Na+/K+ and the Na+/H+ antiporter membrane ionic pumps. Sperm viability was assessed using the eosin-nigrosin live/dead stain. Species-specific differences occurred in response to hypertonic conditions with crane sperm remaining viable under extreme hypertonicity (3000 mOsm/kg), whereas turkey sperm viability was compromised with only slightly hypertonic (500 mOsm/kg) conditions. The timing of spermolysis under hypertonic conditions was also species-specific, with a shorter interval for turkey (2 min) than crane (10 min) sperm. Turkey sperm osmotolerance was slightly improved by lowering the incubation temperature from 21 to 4 ?C. Pre-equilibrating sperm with DMA reduced the incidence of hypertonic spermolysis only in the crane, at both room and refrigeration temperature. Inhibiting the Na+/K+ and the Na+/H+ antiporter membrane ion pumps did not impair resistance of crane and turkey spermatozoa to hypertonic stress; pump inhibition actually increased turkey sperm survival compared to control sperm. Results demonstrate marked species specificity in osmotolerance between crane and turkey sperm, as well as in the way temperature and time of exposure affect sperm survival under hypertonic conditions. Differences are independent of the role of osmotic pumps in these species.

  11. Alkaline Response of a Halotolerant Alkaliphilic Halomonas Strain and Functional Diversity of Its Na+(K+)/H+ Antiporters*

    PubMed Central

    Cheng, Bin; Meng, Yiwei; Cui, Yanbing; Li, Chunfang; Tao, Fei; Yin, Huijia; Yang, Chunyu; Xu, Ping

    2016-01-01

    Halomonas sp. Y2 is a halotolerant alkaliphilic strain from Na+-rich pulp mill wastewater with high alkalinity (pH >11.0). Transcriptome analysis of this isolate revealed this strain may use various transport systems for pH homeostasis. In particular, the genes encoding four putative Na+/H+ antiporters were differentially expressed upon acidic or alkaline conditions. Further evidence, from heterologous expression and mutant studies, suggested that Halomonas sp. Y2 employs its Na+/H+ antiporters in a labor division way to deal with saline and alkaline environments. Ha-NhaD2 displayed robust Na+(Li+) resistance and high transport activities in Escherichia coli; a ΔHa-nhaD2 mutant exhibited growth inhibition at high Na+(Li+) concentrations at pH values of 6.2, 8.0, and 10.0, suggesting its physiological role in osmotic homeostasis. In contrast, Ha-NhaD1 showed much weaker activities in ion exporting and pH homeostasis. Ha-Mrp displayed a combination of properties similar to those of Mrp transporters from some Bacillus alkaliphiles and neutrophiles. This conferred obvious Na+(Li+, K+) resistance in E. coli-deficient strains, as those ion transport spectra of some neutrophil Mrp antiporters. Conversely, similar to the Bacillus alkaliphiles, Ha-Mrp showed central roles in the pH homeostasis of Halomonas sp. Y2. An Ha-mrp-disrupted mutant was seriously inhibited by high concentrations of Na+(Li+, K+) but only under alkaline conditions. Ha-NhaP was determined to be a K+/H+ antiporter and shown to confer strong K+ resistance both at acidic and alkaline stresses. PMID:27777302

  12. NHERF2/NHERF3 Protein Heterodimerization and Macrocomplex Formation Are Required for the Inhibition of NHE3 Activity by Carbachol*

    PubMed Central

    Yang, Jianbo; Singh, Varsha; Chen, Tian-E; Sarker, Rafiquel; Xiong, Lishou; Cha, Boyoung; Jin, Shi; Li, Xuhang; Tse, C. Ming; Zachos, Nicholas C.; Donowitz, Mark

    2014-01-01

    NHERF1, NHERF2, and NHERF3 belong to the NHERF (Na+/H+ exchanger regulatory factor) family of PSD-95/Discs-large/ZO-1 (PDZ) scaffolding proteins. Individually, each NHERF protein has been shown to be involved in the regulation of multiple receptors or transporters including Na+/H+ exchanger 3 (NHE3). Although NHERF dimerizations have been reported, results have been inconsistent, and the physiological function of NHERF dimerizations is still unknown. The current study semiquantitatively compared the interaction strength among all possible homodimerizations and heterodimerizations of these three NHERF proteins by pulldown and co-immunoprecipitation assays. Both methods showed that NHERF2 and NHERF3 heterodimerize as the strongest interaction among all NHERF dimerizations. In vivo NHERF2/NHERF3 heterodimerization was confirmed by FRET and FRAP (fluorescence recovery after photobleach). NHERF2/NHERF3 heterodimerization is mediated by PDZ domains of NHERF2 and the C-terminal PDZ domain recognition motif of NHERF3. The NHERF3-4A mutant is defective in heterodimerization with NHERF2 and does not support the inhibition of NHE3 by carbachol. This suggests a role for NHERF2/NHERF3 heterodimerization in the regulation of NHE3 activity. In addition, both PDZ domains of NHERF2 could be simultaneously occupied by NHERF3 and another ligand such as NHE3, α-actinin-4, and PKCα, promoting formation of NHE3 macrocomplexes. This study suggests that NHERF2/NHERF3 heterodimerization mediates the formation of NHE3 macrocomplexes, which are required for the inhibition of NHE3 activity by carbachol. PMID:24867958

  13. Protective effect of exogenous hydrogen sulfide on pulmonary artery endothelial cells by suppressing endoplasmic reticulum stress in a rat model of chronic obstructive pulmonary disease.

    PubMed

    Ding, Hai-Bo; Liu, Kai-Xiong; Huang, Jie-Feng; Wu, Da-Wen; Chen, Jun-Ying; Chen, Qing-Shi

    2018-06-13

    Chronic obstructive pulmonary disease (COPD) is a multicomponent disorder characterized by inflammation, representing a significant leading cause of chronic morbidity and mortality. Reports have implicated hydrogen sulfide (H 2 S) in both the pathology and treatment of COPD. The present study aimed to explore the effects involved with exogenous H 2 S on endoplasmic reticulum stress (ERS) and pulmonary artery endothelial cells (PAECs) in a rat model of COPD. Rat models of COPD were successfully established by means of passive smoke exposure and intratracheal injection with lipopolysaccharide (LPS). Pulmonary function tests were performed and histopathological changes were observed. The expression of ERS markers, glucose-regulated protein-78 (GRP78), and C/EBP homologous protein (CHOP) and caspase-12, associated with ERS-induced apoptosis, were determined by western blot and immunohistochemistry methods. TUNEL assay was applied to determine the apoptosis index (AI) in PAECs. Treatment with NaHS was followed by the exhibition of markedly increased forced expiratory volume over 0.3 s (FEV0.3)/forced vital capacity (FVC) and dynamic lung compliance as well as integral optical density (IOD), with decreased RI among COPD rats. Western blot analysis, immunohistochemistry and TUNEL assay results revealed there to be reduced expressions of GRP78, CHOP and caspase-12 in the lung tissues and AI of PAECs, post NaHS treatment. The key findings of the current study highlight ERS in COPD rats, as well as well as reduced apoptosis in PAECs in connection with exogenous H 2 S by suppressing ERS. Copyright © 2018. Published by Elsevier Masson SAS.

  14. BDNF/TrkB Pathway Mediates the Antidepressant-Like Role of H2S in CUMS-Exposed Rats by Inhibition of Hippocampal ER Stress.

    PubMed

    Wei, Le; Kan, Li-Yuan; Zeng, Hai-Ying; Tang, Yi-Yun; Huang, Hong-Lin; Xie, Ming; Zou, Wei; Wang, Chun-Yan; Zhang, Ping; Tang, Xiao-Qing

    2018-06-01

    Our previous works have shown that hydrogen sulfide (H 2 S) significantly attenuates chronic unpredictable mild stress (CUMS)-induced depressive-like behaviors and hippocampal endoplasmic reticulum (ER) stress. Brain-derived neurotrophic factor (BDNF) generates an antidepressant-like effect by its receptor tyrosine protein kinase B (TrkB). We have previously found that H 2 S upregulates the expressions of BDNF and p-TrkB in the hippocampus of CUMS-exposed rats. Therefore, the present work was to explore whether BDNF/TrkB pathway mediates the antidepressant-like role of H 2 S by blocking hippocampal ER stress. We found that treatment with K252a (an inhibitor of BDNF/TrkB pathway) significantly increased the immobility time in the forced swim test and tail suspension test and increased the latency to feed in the novelty-suppressed feeding test in the rats cotreated with sodium hydrosulfide (NaHS, a donor of H 2 S) and CUMS. Similarly, K252a reversed the protective effect of NaHS against CUMS-induced hippocampal ER stress, as evidenced by increases in the levels of ER stress-related proteins, glucose-regulated protein 78, CCAAT/enhancer binding protein homologous protein and cleaved caspase-12. Taken together, our results suggest that BDNF/TrkB pathway plays an important mediatory role in the antidepressant-like action of H 2 S in CUMS-exposed rats, which is by suppression of hippocampal ER stress. These data provide a novel mechanism underlying the protection of H 2 S against CUMS-induced depressive-like behaviors.

  15. Monetite formed in mixed solvents of water and ethylene glycol and its transformation to hydroxyapatite.

    PubMed

    Ma, Ming-Guo; Zhu, Ying-Jie; Chang, Jiang

    2006-07-27

    Agglomerated nanorods of hydroxyapatite have been synthesized using monetite as a precursor in a NaOH solution. Monetite consisting of nanosheets has been successfully synthesized by a one-step microwave-assisted method using CaCl(2).2.5H(2)O, NaH(2)PO(4), and sodium dodecyl sulfate (SDS) in water/ethylene glycol (EG) mixed solvents. The effects of the molar ratio of water to EG and the reaction time on the products were investigated. The products were characterized by X-ray powder diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and Fourier transform infrared spectrometry (FTIR).

  16. Towards the production of salt-tolerant crops.

    PubMed

    Barkla, B J; Vera-Estrella, R; Pantoja, O

    1999-01-01

    Crop production is affected by numerous environmental factors, with soil salinity and drought having the most detrimental effects. Attempts to improve yield under stress conditions by plant breeding have been unsuccessful, primarily due to the multigenic origin of the adaptive responses. The transfer of genes through genetic engineering of crop plants appears more feasible. Important adaptive mechanisms targeted for potential gene transfer would be the tonoplast Na+/H+ antiport, compatible solute synthesis and, regulation of water channel activity and expression, mechanisms involved in cellular osmoregulation. In this review we discuss recent advances in our understanding of these adaptive mechanisms.

  17. Mechanisms of tubular sodium chloride transport.

    PubMed

    Venkatesh, S; Schrier, R W; Andreoli, T E

    1998-11-01

    Extracellular fluid volume is determined by sodium and its accompanying anions. There are control mechanisms which regulate sodium balance in the body. These include high and low pressure baroreceptors, intrarenal baroreceptors, renal autoregulation, tubuloglomerular feedback, aldosterone, and numerous other physical and hormonal factors. Sodium transport by the nephron involves active and passive processes which occur in several different nephron segments. Mechanisms of cotransport, Na(+)-H+ exchange, antiporters and ion-specific channels are all utilized by the nephron to maintain sodium balance. These regulatory factors and transport mechanisms for sodium in the kidney will he discussed in detail.

  18. Verknüpfung von DQ-Indikatoren mit KPIs und Auswirkungen auf das Return on Investment

    NASA Astrophysics Data System (ADS)

    Block, Frank

    Häufig ist nicht klar, welche Beziehungen zwischen Datenqualitätsindikatoren (DQI, Definition folgt weiter unten) und Key Performance Indicators (KPI, s. Abschnitt 1.3 für weitere Details) eines Unternehmens oder einer Organisation bestehen. Dies ist insbesondere deshalb von Bedeutung, da die Kenntnis dieser Beziehungen maßgeblich die Ausprägung eines Datenqualitätsprojekts beeinflusst. Sie ist als Entscheidungsgrundlage unabdingbar und gibt Antworten auf folgende Fragen: Was kostet unserem Unternehmen/unserer Organisation1 schlechte Datenqualität? Können wir uns das leisten?

  19. Probleme bei der Digitalisierung analoger Messwerte

    NASA Astrophysics Data System (ADS)

    Plaßmann, Wilfried

    Messwerte liegen häufig in analoger Form als Spannungswerte vor. Sie werden in eine digital kodierte Form umgesetzt, wenn eine (nahezu) fehlerfreie Übertragung erforderlich ist, wenn Signalverläufe gespeichert werden sollen, wenn eine Weiterverarbeitung erfolgen soll oder wenn Messungen mit sehr geringem Messfehler notwendig sind. Hier soll auf einige Probleme, die durch die Umsetzung entstehen, aus messtechnischer Sicht eingegangen werden. Stichworte: Fehler bei der Digitalisierung; Signal-Quantisierungsgeräusch-Abstand; Verbesserung des Signal-Rausch-Verhältnisses; Abtast-Halte-Glied; Aliasing; Erfassung von Momentanwerten.

  20. Regler

    NASA Astrophysics Data System (ADS)

    Wellenreuther, Günter; Zastrow, Dieter

    Aufgabe der Regler ist es, bei Abweichung der Regelgröße x von der Führungsgröße w die Reglerausgangsgröße y R so zu verändern, dass die Regelgröße x in möglichst kurzer Zeit optimal an die Führungsgröße w angeglichen wird. Ursache für die Abweichung kann eine aufgetretene Störgröße z oder die veränderte Führungsgröße w sein.

  1. Einführung als Lesehilfe

    NASA Astrophysics Data System (ADS)

    Zeh, H. Dieter

    Fast alle Beiträge dieses Sammelbands sind unabhängig voneinander entstanden, so dass sie im Prinzip auch unabhängig voneinander gelesen werden können. Diese Tatsache erklärt auch einige Wiederholungen - vornehmlich jedoch von Argumenten, die in der Literatur immer wieder missverständlich oder falsch wiedergegeben werden. Es dürfte aber trotzdem hilfreich für den Leser sein, sich für eine bestimmte Reihenfolge zu entscheiden, die von seinen Interessen und seinem Vorwissen abhängen muss.

  2. Hydrogen sulfide ameliorated L-NAME-induced hypertensive heart disease by the Akt/eNOS/NO pathway.

    PubMed

    Jin, Sheng; Teng, Xu; Xiao, Lin; Xue, Hongmei; Guo, Qi; Duan, Xiaocui; Chen, Yuhong; Wu, Yuming

    2017-12-01

    Reductions in hydrogen sulfide (H 2 S) production have been implicated in the pathogenesis of hypertension; however, no studies have examined the functional role of hydrogen sulfide in hypertensive heart disease. We hypothesized that the endogenous production of hydrogen sulfide would be reduced and exogenous hydrogen sulfide would ameliorate cardiac dysfunction in N ω -nitro- L-arginine methyl ester ( L-NAME)-induced hypertensive rats. Therefore, this study investigated the cardioprotective effects of hydrogen sulfide on L-NAME-induced hypertensive heart disease and explored potential mechanisms. The rats were randomly divided into five groups: Control, Control + sodium hydrosulfide (NaHS), L-NAME, L-NAME + NaHS, and L-NAME + NaHS + glibenclamide (Gli) groups. Systolic blood pressure was monitored each week. In Langendorff-isolated rat heart, cardiac function represented by ±LV dP/dt max and left ventricular developing pressure was recorded after five weeks of treatment. Hematoxylin and Eosin and Masson's trichrome staining and myocardium ultrastructure under transmission electron microscopy were used to evaluate cardiac remodeling. The plasma nitric oxide and hydrogen sulfide concentrations, as well as nitric oxide synthases and cystathionine-γ-lyase activity in left ventricle tissue were determined. The protein expression of p-Akt, Akt, p-eNOS, and eNOS in left ventricle tissue was analyzed using Western blot. After five weeks of L-NAME treatment, there was a time-dependent hypertension, cardiac remodeling, and dysfunction accompanied by a decrease in eNOS phosphorylation, nitric oxide synthase activity, and nitric oxide concentration. Meanwhile, cystathionine-γ-lyase activity and hydrogen sulfide concentration were also decreased. NaHS treatment significantly increased plasma hydrogen sulfide concentration and subsequently promoted the Akt/eNOS/NO pathway which inhibited the development of hypertension and attenuated cardiac remodeling and

  3. Intracellular pH Regulation in Cultured Astrocytes from Rat Hippocampus

    PubMed Central

    Bevensee, Mark O.; Weed, Regina A.; Boron, Walter F.

    1997-01-01

    We studied the regulation of intracellular pH (pHi) in single cultured astrocytes passaged once from the hippocampus of the rat, using the dye 2′,7′-biscarboxyethyl-5,6-carboxyfluorescein (BCECF) to monitor pHi. Intrinsic buffering power (βI) was 10.5 mM (pH unit)−1 at pHi 7.0, and decreased linearly with pHi; the best-fit line to the data had a slope of −10.0 mM (pH unit)−2. In the absence of HCO3 −, pHi recovery from an acid load was mediated predominantly by a Na-H exchanger because the recovery was inhibited 88% by amiloride and 79% by ethylisopropylamiloride (EIPA) at pHi 6.05. The ethylisopropylamiloride-sensitive component of acid extrusion fell linearly with pHi. Acid extrusion was inhibited 68% (pHi 6.23) by substituting Li+ for Na+ in the bath solution. Switching from a CO2/HCO3 −-free to a CO2/HCO3 −-containing bath solution caused mean steady state pHi to increase from 6.82 to 6.90, due to a Na+-driven HCO3 − transporter. The HCO3 −-induced pHi increase was unaffected by amiloride, but was inhibited 75% (pHi 6.85) by 400 μM 4,4′-diisothiocyanatostilbene-2,2′-disulfonic acid (DIDS), and 65% (pHi 6.55–6.75) by pretreating astrocytes for up to ∼6.3 h with 400 μM 4-acetamide-4′-isothiocyanatostilbene-2,2′-disulfonic acid (SITS). The CO2/HCO3 −-induced pHi increase was blocked when external Na+ was replaced with N-methyl-d-glucammonium (NMDG+). In the presence of HCO3 −, the Na+-driven HCO3 − transporter contributed to the pHi recovery from an acid load. For example, HCO3 − shifted the plot of acid-extrusion rate vs. pHi by 0.15–0.3 pH units in the alkaline direction. Also, with Na-H exchange inhibited by amiloride, HCO3 − increased acid extrusion 3.8-fold (pHi 6.20). When astrocytes were acid loaded in amiloride, with Li+ as the major cation, HCO3 − failed to elicit a substantial increase in pHi. Thus, Li+ does not appear to substitute well for Na+ on the HCO3 − transporter. We conclude that an amiloride

  4. Ionic molal conductivities, activity coefficients, and dissociation constants of HAsO42− and H2AsO4− from 5 to 90°C and ionic strengths from 0.001 up to 3 mol kg−1 and applications in natural systems

    USGS Publications Warehouse

    Zhu, Xiangyu; Nordstrom, D. Kirk; McCleskey, R. Blaine; Wang, Rucheng

    2016-01-01

    Arsenic is known to be one of the most toxic inorganic elements, causing worldwide environmental contamination. However, many fundamental properties related to aqueous arsenic species are not well known which will inhibit our ability to understand the geochemical behavior of arsenic (e.g. speciation, transport, and solubility). Here, the electrical conductivity of Na2HAsO4 solutions has been measured over the concentration range of 0.001–1 mol kg−1 and the temperature range of 5–90°C. Ionic strength and temperature-dependent equations were derived for the molal conductivity of HAsO42−and H2AsO4− aqueous ions. Combined with speciation calculations and the approach used by McCleskey et al. (2012b), these equations can be used to calculate the electrical conductivities of arsenic-rich waters having a large range of effective ionic strengths (0.001–3 mol kg−1) and temperatures (5–90°C). Individual ion activity coefficients for HAsO42− and H2AsO4− in the form of the Hückel equation were also derived using the mean salt method and the mean activity coefficients of K2HAsO4 (0.001–1 mol kg−1) and KH2AsO4 (0.001–1.3 mol kg−1). A check on these activity coefficients was made by calculating mean activity coefficients for Na2HAsO4 and NaH2AsO4 solutions and comparing them to measured values. At the same time Na-arsenate complexes were evaluated. The NaH2AsO40 ion pair is negligible in NaH2AsO4 solutions up to 1.3 mol kg−1. The NaHAsO4− ion pair is important in NaHAsO4 solutions >0.1 mol kg−1 and the formation constant of 100.69 was confirmed. The enthalpy, entropy, free energy and heat capacity for the second and third arsenic acid dissociation reactions were calculated from pH measurements. These properties have been incorporated into a widely used geochemical calculation code WATEQ4F and applied to natural arsenic waters. For arsenic spiked water samples from Yellowstone National Park, the mean difference between the

  5. Liquid Biopsy zur Überwachung von Melanompatienten.

    PubMed

    Gaiser, Maria Rita; von Bubnoff, Nikolas; Gebhardt, Christoffer; Utikal, Jochen Sven

    2018-04-01

    In den letzten sechs Jahren wurden verschiedene innovative systemische Therapien zur Behandlung des metastasierten malignen Melanoms (MM) entwickelt. Die konventionelle Chemotherapie wurde durch neuartige Primärtherapien abgelöst, darunter systemische Immuntherapien (Anti-CTLA4- und Anti-PD1-Antikörper; Zulassung von Anti-PDL1-Antikörpern erwartet) und Therapien, die gegen bestimmte Mutationen gerichtet sind (BRAF, NRAS und c-KIT). Daher stehen die behandelnden Ärzte neuen Herausforderungen gegenüber, beispielsweise der Stratifizierung von Patienten für geeignete Behandlungen und der Überwachung von Langzeit-Respondern auf Progression. Folglich werden zuverlässige Methoden zur Überwachung von Krankheitsprogression oder Behandlungsresistenz benötigt. Lokalisierte und fortgeschrittene Krebserkrankungen können zur Bildung zirkulierender Tumorzellen und Tumor-DNA (ctDNA) führen, die sich in Proben von peripherem Blut nachweisen und quantifizieren lassen (Liquid Biopsy). Im Fall von Melanompatienten können die Ergebnisse von Liquid Biopsy als neuartige prädiktive Biomarker bei therapeutischen Entscheidungen hilfreich sein, insbesondere im Zusammenhang mit mutationsbasierten zielgerichteten Therapien. Die Herausforderungen bei der Anwendung der Liquid Biopsy beinhalten strikte Kriterien für den Phänotyp der zirkulierenden MM-Zellen oder ihrer Fragmente und die Instabilität von ctDNA im Blut. In diesem Übersichtsartikel diskutieren wir die Beschränkungen der Liquid Biopsy hinsichtlich ihrer Anwendung in der Routinediagnostik. © 2018 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

  6. Grenzhandel am Hochrhein. Schweizer Franken - Potenzial oder Risiko für den deutschen Handel?

    NASA Astrophysics Data System (ADS)

    Emmerling, Sandra

    2017-09-01

    Retail shopping in Hochrhein on the tri-border region is affected by the shopping behaviour of the Swiss households. On the one hand the German retail in the German border towns was able to develop dynamically and tap the demand from regions beyond the border. A market-relevant example was used to investigate the question of whether these cross-border inflows should be considered an area of potential growth or risk for German retail. On the other hand, together with e-commerce the shopping tourism leads to a tilt in spatial structure in the Swiss border regions. The demand and strategy for sustainable city and regional development are discussed from the perspective of retail, city planning and market research.

  7. Renaissance des Dorfladens oder Versorgungswüsten?. Erfahrungen und Lernpotenziale am Beispiel Schleswig-Holstein

    NASA Astrophysics Data System (ADS)

    Jürgens, Ulrich

    2017-06-01

    It has become more and more complicated for the customers to make their food shopping in local environments because smaller shops close down and the distances to supermarkets and discount stores have increased, especially in rural areas. The paper will discuss which alternatives of food retailing exist outside the supermarket world and analyzes the strengths and weaknesses of shop formats on the micro level. The statements are based on a conscious selection of different shop formats and expert interviews in rural areas of the province of Schleswig-Holstein.

  8. Zum Auf und Ab des Meeresspiegels in Skandinavien: Langer Streit um Eustasie oder Isostasie

    NASA Astrophysics Data System (ADS)

    Seibold, Eugen; Seibold, Ilse

    2012-03-01

    The phenomenon of the rise of the Scandinavian shield during the Holocene and the concomitant fall in level of the Baltic Sea has been investigated for centuries. Already in medieval times, there were reports about the coastlines of the Gulf of Bothnia that are full of relevant observations. During the eighteenth century, scientists such as Celsius and Linnaeus collected observations such as these. The result was that the search for the possible explanations of this rise-and-fall phenomenon intensified. The generally favoured explanation was that there was an active sinking of sea level in the Baltic rather than an active rising of the land surface in Fennoscandia. This was because water was seen as mobile, in contrast to a "terra firma". The relevant discussion was often emotional, and here, we try to illustrate it using material from the Geologenarchiv Freiburg (von Hoff, von Buch and Goethe). No more than a few decades later, it became obvious by the theory of Ice Age that both the sea level and the land could be mobile (eustatic sea level changes—glacial isostasy). Additionally, of course, plate tectonics had some influence: Norway is situated at the western end of the Eurasian plate and is part of a passive continental margin. There are still open research problems, many of which can be addressed using modern methods of satellite-based geophysics and geodesy. Some other aspects as the permanent uplift trend of Scandinavia since the Cambrium or the rhythmic to and fro of magma in the upper mantle during the Pleistocene are mentioned.

  9. Einsteins Spuren in den Archiven der Wissenschaft: Physikgeschichte

    NASA Astrophysics Data System (ADS)

    Marx, Werner

    2005-07-01

    Die Erwähnungen und Zitierungen von Einsteins Arbeiten dokumentieren lediglich den quantifizierbaren Anteil von Einsteins Beitrag zur Physik. Gleichwohl belegen sie die außergewöhnliche Resonanz und Langzeitwirkung seiner Arbeiten. Die Häufigkeit der Zitierungen entspricht nicht der allgemeinen Einschätzung ihrer Bedeutung. Insbesondere die Pionierarbeiten werden inzwischen als bekannt vorausgesetzt und nicht mehr explizit zitiert. Interessanterweise ist seine nach 1945 meist zitierte Arbeit nicht eine der Pionierarbeiten zur Quantenphysik oder Relativitätstheorie, sondern jene aus dem Jahr 1935 zum berühmten Einstein-Podolsky-Rosen-Paradoxon.

  10. Mathematisches Bewusstsein

    NASA Astrophysics Data System (ADS)

    Kaenders, Rainer; Kvasz, Ladislav

    Wenn jemand sagt, dass ein Bus um 9 Uhr abfährt - weiß man es dann? Angenommen, man ist darüber unterrichtet, dass die Busse unter der Woche immer zur vollen Stunde abfahren - von 7 Uhr morgens bis 7 Uhr abends, weiß man es dann mit dem Wissen um diese allgemeine Regel besser, dass der Bus um 9 Uhr abfährt? Macht es einen Unterschied, ob man den Fahrplan erstellt, den Bus lenkt oder nur mitfährt, um sich dieser Tatsache bewusst zu sein?

  11. Space infrared telescope pointing control system. Automated star pattern recognition

    NASA Technical Reports Server (NTRS)

    Powell, J. D.; Vanbezooijen, R. W. H.

    1985-01-01

    The Space Infrared Telescope Facility (SIRTF) is a free flying spacecraft carrying a 1 meter class cryogenically cooled infrared telescope nearly three oders of magnitude most sensitive than the current generation of infrared telescopes. Three automatic target acquisition methods will be presented that are based on the use of an imaging star tracker. The methods are distinguished by the number of guidestars that are required per target, the amount of computational capability necessary, and the time required for the complete acquisition process. Each method is described in detail.

  12. Nichtperiodische zeitkontinuierliche Signale

    NASA Astrophysics Data System (ADS)

    Plaßmann, Wilfried

    Nichtperiodische Signale haben eine große Bedeutung für die Nachrichten- und Datenübertragung, weil Information nur in nichtdeterministischen Signalen enthalten ist (Teil "Nachrichtentechnik", Abschn. 92.4.1). Aber auch für die Energie- und Regelungstechnik sind sie von Interesse, weil sie entweder Ein- und Ausschaltvorgänge erfassen oder den Übergang von einem momentan stationären Zustand in einen neuen darstellen (Kurzschluss im Energieversorgungsnetz, Auftreten einer Störgröße im Regelsystem). Die Fourier- und die Laplacetransformation können bei nichtperiodischen zeitkontinuierlichen Signalen eingesetzt werden.

  13. Airborne laser-spark for ambient desorption/ionisation.

    PubMed

    Bierstedt, Andreas; Riedel, Jens

    Desorption als auch die Ionisation erfolgen hierbei durch ein laserbetriebenes Luftplasma. Die Abwesenheit fester oder flüssiger Elektroden hat zur Folge, dass die Methode weder unter chemischen Interferenzen noch unter Verschleiß durch Korrosionsbrand oder abgetragenes Elektrodenmaterial leidet. Insgesamt betrachtet herrscht in dem Plasma Elektroneutralität, wodurch Aufladungseffekte minimiert werden, die andernfalls zu einer langfristigenÄderung der Flugbahnen von Ionen während der Experimente führen kann. In dem Ansatz eine freischwebende Luftentladung bei Atmosphärendruck zu verwenden agiert die Luft nicht nur als Plasmamedium sondert dient zusätzlich als Badgas für die stoßinduzierte Kühlung der entstehenden Ionen. Die Ionisierung der Analytmoleküle erfolgt nicht unmittelbar im Plasma sondern in dessen direkter Umgebung durch Wechselwirkung mit freigesetzten ionischen Luftspezies, freien Elektronen oder Photonen im kurzwelligen ultravioletten Bereich. Jede Laserentladung erzeugt eine hörbare Stoßwelle, in welcher neu produzierte reaktive Spezies freigesetzt werden, welche sich konzentrisch ausbreiten, so dass eine Diffusion der Analytmoleküle ins heiße Innere des Plasmas verhindert wird. Daraus folgt, dass im Interaktionsvolumen zwischen Plasma und Analyt der Temperaturgrenzwert für eine thermische Dissoziation oder Fragmentierung der Moleküle nicht überschritten wird. Experimentell konnte belegt werden, dass das vorgestellte Ionisierungsschema sehr unselektiv bezüglich der chemischen Analytklasse ist und kaum Fragmentierungsprodukte beobachtet werden können. Messungen einer breitgefächerten Auswahl unterschiedlicher Testsubstanzen, wie beispielsweise polarer und unpolarer Kohlenwasserstoffe, Zuckern, niedermolekularer pharmazeutischer Wirkstoffe, sowie natürlicher Biomoleküle in Lebensmittelproben unmittelbar aus ihren komplexen Matrizes, führten zu aussagekräftigen Massenspektren. Zumal das Lasermedium feuchte Luft ist, scheint der

  14. Bicarbonate-dependent and -independent intracellular pH regulatory mechanisms in rat hepatocytes. Evidence for Na+-HCO3- cotransport.

    PubMed Central

    Gleeson, D; Smith, N D; Boyer, J L

    1989-01-01

    Using the pH-sensitive dye 2,7-bis(carboxyethyl)-5(6)-carboxy-fluorescein and a continuously perfused subconfluent hepatocyte monolayer cell culture system, we studied rat hepatocyte intracellular pH (pHi) regulation in the presence (+HCO3-) and absence (-HCO3-) of bicarbonate. Baseline pHi was higher (7.28 +/- 09) in +HCO3- than in -HCO3- (7.16 +/- 0.14). Blocking Na+/H+ exchange with amiloride had no effect on pHi in +HCO3- but caused reversible 0.1-0.2-U acidification in -HCO3- or in +HCO3- after preincubation in the anion transport inhibitor 4,4'-diisothiocyano-2,2'-disulfonic acid stilbene (DIDS). Acute Na+ replacement in +HCO3- alos caused acidification which was amiloride independent but DIDS inhibitible. The recovery of pHi from an intracellular acid load (maximum H+ efflux rate) was 50% higher in +HCO3- than in -HCO3-. Amiloride inhibited H+ effluxmax by 75% in -HCO3- but by only 27% in +HCO3-. The amiloride-independent pHi recovery in +HCO3- was inhibited 50-63% by DIDS and 79% by Na+ replacement but was unaffected by depletion of intracellular Cl-, suggesting that Cl-/HCO3- exchange is not involved. Depolarization of hepatocytes (raising external K+ from 5 to 25 mM) caused reversible 0.05-0.1-U alkalinization, which, however, was neither Na+ nor HCO3- dependent, nor DIDS inhibitible, findings consistent with electroneutral HCO3- transport. We conclude that Na+-HCO3- cotransport, in addition to Na+/H+ exchange, is an important regulator of pHi in rat hepatocytes. PMID:2544626

  15. Horizontal Transfer of phnAc Dioxygenase Genes within One of Two Phenotypically and Genotypically Distinctive Naphthalene-Degrading Guilds from Adjacent Soil Environments

    PubMed Central

    Wilson, Mark S.; Herrick, James B.; Jeon, Che Ok; Hinman, David E.; Madsen, Eugene L.

    2003-01-01

    Several distinct naphthalene dioxygenases have been characterized to date, which provides the opportunity to investigate the ecological significance, relative distribution, and transmission modes of the different analogs. In this study, we showed that a group of naphthalene-degrading isolates from a polycyclic aromatic hydrocarbon (PAH)-contaminated hillside soil were phenotypically and genotypically distinct from naphthalene-degrading organisms isolated from adjacent, more highly contaminated seep sediments. Mineralization of 14C-labeled naphthalene by soil slurries suggested that the in situ seep community was more acclimated to PAHs than was the in situ hillside community. phnAc-like genes were present in diverse naphthalene-degrading isolates cultured from the hillside soil, while nahAc-like genes were found only among isolates cultured from the seep sediments. The presence of a highly conserved nahAc allele among gram-negative isolates from the coal tar-contaminated seep area provided evidence for in situ horizontal gene transfer and was reported previously (J. B. Herrick, K. G. Stuart-Keil, W. C. Ghiorse, and E. L. Madsen, Appl. Environ. Microbiol. 63:2330-2337, 1997). Natural horizontal transfer of the phnAc sequence was also suggested by a comparison of the phnAc and 16S ribosomal DNA sequences of the hillside isolates. Analysis of metabolites produced by cell suspensions and patterns of amplicons produced by PCR analysis suggested both genetic and metabolic diversity among the naphthalene-degrading isolates of the contaminated hillside. These results provide new insights into the distribution, diversity, and transfer of phnAc alleles and increase our understanding of the acclimation of microbial communities to pollutants. PMID:12676698

  16. Expression of ion transport-associated proteins in human efferent and epididymal ducts.

    PubMed

    Kujala, Minna; Hihnala, Satu; Tienari, Jukka; Kaunisto, Kari; Hästbacka, Johanna; Holmberg, Christer; Kere, Juha; Höglund, Pia

    2007-04-01

    Appropriate intraluminal microenvironment in the epididymis is essential for maturation of sperm. To clarify whether the anion transporters SLC26A2, SLC26A6, SLC26A7, and SLC26A8 might participate in generating this proper intraluminal milieu, we studied the localization of these proteins in the human efferent and the epididymal ducts by immunohistochemistry. In addition, immunohistochemistry of several SLC26-interacting proteins was performed: the Na(+)/H(+) exchanger 3 (NHE3), the Cl(-) channel cystic fibrosis transmembrane conductance regulator (CFTR), the proton pump V-ATPase, their regulator Na(+)/H(+) exchanger regulating factor 1 (NHERF-1), and carbonic anhydrase II (CAII). Our results show that SLC26A6, CFTR, NHE3, and NHERF-1 are co-expressed on the apical side of the nonciliated cells, and SLC26A2 appears in the cilia of the ciliated cells in the human efferent ducts. In the epididymal ducts, SLC26A6, CFTR, NHERF-1, CAII, and V-ATPase (B and E subunits) were co-localized to the apical mitochondria rich cells, while SLC26A7 was expressed in a subgroup of basal cells. SLC26A8 was not found in the structures studied. This is the first study describing the localization of SLC26A2, A6 and A7, and NHERF-1 in the efferent and the epididymal ducts. Immunolocalization of human CFTR, NHE3, CAII, and V-ATPase in these structures differs partly from previous reports from rodents. Our findings suggest roles for these proteins in male fertility, either independently or through interaction and reciprocal regulation with co-localized proteins shown to affect fertility, when disrupted.

  17. Benzoylsalicylic acid derivatives as defense activators in tobacco and Arabidopsis.

    PubMed

    Kamatham, Samuel; Pallu, Reddanna; Pasupulati, Anil Kumar; Singh, Surya Satyanarayana; Gudipalli, Padmaja

    2017-11-01

    Systemic acquired resistance (SAR) is a long lasting inducible whole plant immunity often induced by either pathogens or chemical elicitors. Salicylic acid (SA) is a known SAR signal against a broad spectrum of pathogens in plants. In a recent study, we have reported that benzoylsalicylic acid (BzSA) is a SAR inducer in tobacco and Arabidopsis plants. Here, we have synthesized BzSA derivatives using SA and benzoyl chlorides of various moieties as substrates. The chemical structures of BzSA derivatives were elucidated using Infrared spectroscopy (IR), Nuclear magnetic spectroscopy (NMR) and High-resolution mass spectrometer (HRMS) analysis. The bioefficacy of BzSA derivatives in inducing defense response against tobacco mosaic virus (TMV) was investigated in tobacco and SA abolished transgenic NahG Arabidopsis plants. Interestingly, pre-treatment of local leaves of tobacco with BzSA derivatives enhanced the expression of SAR genes such as NPR1 [Non-expressor of pathogenesis-related (PR) genes 1], PR and other defense marker genes (HSR203, SIPK, WIPK) in systemic leaves. Pre-treatment of BzSA derivatives reduced the spread of TMV infection to uninfected areas by restricting lesion number and diameter both in local and systemic leaves of tobacco in a dose-dependent manner. Furthermore, pre-treatment of BzSA derivatives in local leaves of SA deficient Arabidopsis NahG plants induced SAR through AtPR1 and AtPR5 gene expression and reduced leaf necrosis and curling symptoms in systemic leaves as compared to BzSA. These results suggest that BzSA derivatives are potent SAR inducers against TMV in tobacco and Arabidopsis. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Understanding the role of Ti in reversible hydrogen storage as sodium alanate: a combined experimental and density functional theoretical approach.

    PubMed

    Chaudhuri, Santanu; Graetz, Jason; Ignatov, Alex; Reilly, James J; Muckerman, James T

    2006-09-06

    We report the results of an experimental and theoretical study of hydrogen storage in sodium alanate (NaAlH(4)). Reversible hydrogen storage in this material is dependent on the presence of 2-4% Ti dopant. Our combined study shows that the role of Ti may be linked entirely to Ti-containing active catalytic sites in the metallic Al phase present in the dehydrogenated NaAlH(4). The EXAFS data presented here show that dehydrogenated samples contain a highly disordered distribution of Ti-Al distances with no long-range order beyond the second coordination sphere. We have used density functional theory techniques to calculate the chemical potential of possible Ti arrangements on an Al(001) surface for Ti coverages ranging from 0.125 to 0.5 monolayer (ML) and have identified those that can chemisorb molecular hydrogen via spontaneous or only moderately activated pathways. The chemisorption process exhibits a characteristic nodal symmetry property for the low-barrier sites: the incipient doped surface-H(2) adduct's highest occupied molecular orbital (HOMO) incorporates the sigma antibonding molecular orbital of hydrogen, allowing the transfer of charge density from the surface to dissociate the molecular hydrogen. This work also proposes a plausible mechanism for the transport of an aluminum hydride species back into the NaH lattice that is supported by Car-Parrinello molecular dynamics (CPMD) simulations of the stability and mobility of aluminum clusters (alanes) on Al(001). As an experimental validation of the proposed role of titanium and the subsequent diffusion of alanes, we demonstrate experimentally that AlH(3) reacts with NaH to form NaAlH(4) without any requirement of a catalyst or hydrogen overpressure.

  19. Parasitism by Cuscuta pentagona Attenuates Host Plant Defenses against Insect Herbivores1

    PubMed Central

    Runyon, Justin B.; Mescher, Mark C.; De Moraes, Consuelo M.

    2008-01-01

    Considerable research has examined plant responses to concurrent attack by herbivores and pathogens, but the effects of attack by parasitic plants, another important class of plant-feeding organisms, on plant defenses against other enemies has not been explored. We investigated how attack by the parasitic plant Cuscuta pentagona impacted tomato (Solanum lycopersicum) defenses against the chewing insect beet armyworm (Spodoptera exigua; BAW). In response to insect feeding, C. pentagona-infested (parasitized) tomato plants produced only one-third of the antiherbivore phytohormone jasmonic acid (JA) produced by unparasitized plants. Similarly, parasitized tomato, in contrast to unparasitized plants, failed to emit herbivore-induced volatiles after 3 d of BAW feeding. Although parasitism impaired antiherbivore defenses, BAW growth was slower on parasitized tomato leaves. Vines of C. pentagona did not translocate JA from BAW-infested plants: amounts of JA in parasite vines grown on caterpillar-fed and control plants were similar. Parasitized plants generally contained more salicylic acid (SA), which can inhibit JA in some systems. Parasitized mutant (NahG) tomato plants deficient in SA produced more JA in response to insect feeding than parasitized wild-type plants, further suggesting cross talk between the SA and JA defense signaling pathways. However, JA induction by BAW was still reduced in parasitized compared to unparasitized NahG, implying that other factors must be involved. We found that parasitized plants were capable of producing induced volatiles when experimentally treated with JA, indicating that resource depletion by the parasite does not fully explain the observed attenuation of volatile response to herbivore feeding. Collectively, these findings show that parasitic plants can have important consequences for host plant defense against herbivores. PMID:18165323

  20. Parasitism by Cuscuta pentagona attenuates host plant defenses against insect herbivores.

    PubMed

    Runyon, Justin B; Mescher, Mark C; De Moraes, Consuelo M

    2008-03-01

    Considerable research has examined plant responses to concurrent attack by herbivores and pathogens, but the effects of attack by parasitic plants, another important class of plant-feeding organisms, on plant defenses against other enemies has not been explored. We investigated how attack by the parasitic plant Cuscuta pentagona impacted tomato (Solanum lycopersicum) defenses against the chewing insect beet armyworm (Spodoptera exigua; BAW). In response to insect feeding, C. pentagona-infested (parasitized) tomato plants produced only one-third of the antiherbivore phytohormone jasmonic acid (JA) produced by unparasitized plants. Similarly, parasitized tomato, in contrast to unparasitized plants, failed to emit herbivore-induced volatiles after 3 d of BAW feeding. Although parasitism impaired antiherbivore defenses, BAW growth was slower on parasitized tomato leaves. Vines of C. pentagona did not translocate JA from BAW-infested plants: amounts of JA in parasite vines grown on caterpillar-fed and control plants were similar. Parasitized plants generally contained more salicylic acid (SA), which can inhibit JA in some systems. Parasitized mutant (NahG) tomato plants deficient in SA produced more JA in response to insect feeding than parasitized wild-type plants, further suggesting cross talk between the SA and JA defense signaling pathways. However, JA induction by BAW was still reduced in parasitized compared to unparasitized NahG, implying that other factors must be involved. We found that parasitized plants were capable of producing induced volatiles when experimentally treated with JA, indicating that resource depletion by the parasite does not fully explain the observed attenuation of volatile response to herbivore feeding. Collectively, these findings show that parasitic plants can have important consequences for host plant defense against herbivores.

  1. Does treatment by a specialist physiotherapist change pain and function in young adults with symptoms from femoroacetabular impingement? A pilot project for a randomised controlled trial.

    PubMed

    Smeatham, Alison; Powell, Roy; Moore, Sarah; Chauhan, Rohan; Wilson, Matthew

    2017-06-01

    Femoroacetabular impingement (FAI) is recognised as a source of hip pain but the effect of conservative treatment remains untested. This pilot study aimed to inform and evaluate the methods required to conduct a substantive trial comparing the effect of treatment by a physiotherapist versus routine care on the symptoms of FAI. A parallel group, pilot randomised controlled trial (RCT). A single NHS acute hospital trust, Devon, England. 30 adults with symptomatic FAI were recruited. 23 (77%) completed the study. Intervention was 3 months of treatment by a specialist physiotherapist. The control group received routine care. Change in pain and function was measured using a Visual Analogue Scale, Non Arthritic Hip Score (NAHS), Lower Extremity Functional Score (LEFS) and Hip Outcome Score. Participants in the intervention arm undertook a personalised exercise programme to improve pelvic and femoral control plus advice on posture, activity pacing and pain relief. The mean change in NAHS for the intervention group was 12.7 (95% CI 4.7 to 20.7) and 1.8 (95% CI -5.3 to 9.0) in the control group; Median change in LEFS was 11.5 (95% CI 5.0 to 26.0) versus -1.0 (95% CI -7.0 to 4.0). This improvement in LEFS was beyond minimal clinically important difference in the intervention group. Pain scores improved marginally in both groups. Methodological strengths and weaknesses were successfully identified for a substantive study. Further research is needed to evaluate the relative influence of structural and neuromuscular features on symptoms of FAI and the role of conservative treatment. Copyright © 2016 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.

  2. Response of microbial community and catabolic genes to simulated petroleum hydrocarbon spills in soils/sediments from different geographic locations.

    PubMed

    Liu, Q; Tang, J; Liu, X; Song, B; Zhen, M; Ashbolt, N J

    2017-10-01

    Study the response of microbial communities and selected petroleum hydrocarbon (PH)-degrading genes on simulated PH spills in soils/sediments from different geographic locations. A microcosm experiment was conducted by spiking mixtures of petroleum hydrocarbons (PHs) to soils/sediments collected from four different regions of China, including the Dagang Oilfield (DG), Sand of Bohai Sea (SS), Northeast China (NE) and Xiamen (XM). Changes in bacterial community and the abundance of PH-degrading genes (alkB, nah and phe) were analysed by denaturing gradient electrophoresis (DGGE) and qPCR, respectively. Degradation of alkanes and PAHs in SS and NE materials were greater (P < 0·05) than those in DG and XM. Clay content was negatively correlated with the degradation of total alkanes by 112 days and PAHs by 56 days, while total organic carbon content was negatively correlated with initial degradation of total alkanes as well as PAHs. Abundances of alkB, nah and phe genes increased 10- to 100-fold and varied by soil type over the incubation period. DGGE fingerprints identified the dominance of α-, β- and γ-Proteobacteria (Gram -ve) and Actinobacteria (Gram +ve) bacteria associated with degradation of PHs in the materials studied. The geographic divergence resulting from the heterogeneity of physicochemical properties of soils/sediments appeared to influence the abundance of metabolic genes and community structure of microbes capable of degrading PHs. When developing practical in-situ bioremediation approaches for PHs contamination of soils/sediment, appropriate microbial community structures and the abundance of PH-degrading genes appear to be influenced by geographic location. © 2017 The Society for Applied Microbiology.

  3. The impact of dihydrogen phosphate anions on the excited-state proton transfer of harmane. Effect of β-cyclodextrin on these photoreactions.

    PubMed

    Reyman, Dolores; Viñas, Montserrat H; Tardajos, Gloria; Mazario, Eva

    2012-01-12

    Photoinduced proton transfer reactions of harmane (1-methyl-9H-pyrido[3,4-b]indole) (HAR) in the presence of a proton donor/acceptor such as dihydrogen phosphate anions in aqueous solution have been studied by stationary and time-resolved fluorescence spectroscopy. The presence of high amounts of dihydrogen phosphate ions modifies the acid/base properties of this alkaloid. Thus, by keeping the pH constant at pH 8.8 and by increasing the amount of NaH(2)PO(4) in the solution, it is possible to reproduce the same spectral profiles as those obtained in high alkaline solutions (pH >12) in the absence of NaH(2)PO(4). Under these conditions, a new fluorescence profile appears at around 520 nm. This result could be related to the results of a recent investigation which suggests that a high intake of phosphates may promote skin tumorigenesis. The presence of β-cyclodextrin (β-CD) avoids the proton transfer reactions in this alkaloid by means the formation of an inclusion complex between β-CD and HAR. The formation of this complex originates a remarkable enhancement of the emission intensity from the neutral form in contrast to the cationic and zwitterionic forms. A new lifetime was obtained at 360 nm (2.5 ns), which was associated with the emission of this inclusion complex. At this wavelength, the fluorescence intensity decay of HAR can be described by a linear combination of two exponentials. From the ratio between the pre-exponential factors, we have obtained a value of K = 501 M for the equilibrium of formation of this complex.

  4. Effect of type 1 diabetes on the production and vasoactivity of hydrogen sulfide in rat middle cerebral arteries

    PubMed Central

    Streeter, Elosie Y; Badoer, Emilio; Woodman, Owen L; Hart, Joanne L

    2013-01-01

    Hydrogen sulfide (H2S) is produced endogenously in vascular tissue and has both vasoregulation and antioxidant effects. This study examines the effect of diabetes-induced oxidative stress on H2S production and function in rat middle cerebral arteries. Diabetes was induced in rats with streptozotocin (50 mg/kg, i.v.). Middle cerebral artery function was examined using a small vessel myograph and superoxide anion generation measured using nicotinamide adenine dinucleotide phosphate (NADPH)-dependent lucigenin-enhanced chemiluminescence. Cystathionine-γ-lyase (CSE) mRNA expression was measured via RT-PCR. Diabetic rats had elevated blood glucose and significantly reduced cerebral artery endothelial function. Maximum vasorelaxation to the H2S donor NaHS was unaffected in diabetic cerebral arteries and was elicited via a combination of K+, Cl−, and Ca2+ channel modulation, although the contribution of Cl− channels was significantly less in the diabetic cerebral arteries. Vasorelaxation to the H2S precursor l-cysteine and CSE mRNA were significantly increased in diabetic cerebral arteries. Cerebral artery superoxide production was significantly increased in diabetes, but this increase was attenuated ex vivo by incubation with the H2S donor NaHS. These data confirm that cerebral artery endothelial dysfunction and oxidative stress occurs in diabetes. Endogenous H2S production and activity is upregulated in cerebral arteries in this model of diabetes. Vasorelaxation responses to exogenous H2S are preserved and exogenous H2S attenuates the enhanced cerebral artery generated superoxide observed in the diabetic group. These data suggest that upregulation of endogenous H2S in diabetes may play an antioxidant and vasoprotective role. PMID:24303182

  5. Diversity, abundance, and consistency of microbial oxygenase expression and biodegradation in a shallow contaminated aquifer

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Yagi, J.M.; Madsen, E.L.

    The diversity of Rieske dioxygenase genes and short-term temporal variability in the abundance of two selected dioxygenase gene sequences were examined in a naphthalene-rich, coal tar waste-contaminated subsurface study site. Using a previously published PCR-based approach (S. M. Ni Chadhain, R. S. Norman, K. V. Pesce, J. J. Kukor, and G. J. Zylstra, Appl. Environ. Microbiol. 72: 4078-4087, 2006) a broad suite of genes was detected, ranging from dioxygenase sequences associated with Rhodococcus and Sphingomonas to 32 previously uncharacterized Rieske gene sequence clone groups. The nag genes appeared frequently (20% of the total) in two groundwater monitoring wells characterized bymore » low (similar to 10{sup 2} ppb; similar to 1 {mu} M) ambient concentrations of naphthalene. A quantitative competitive PCR assay was used to show that abundances of nag genes (and archetypal nah genes) fluctuated substantially over a 9-month period. To contrast short-term variation with long-term community stability, in situ community gene expression (dioxygenase mRNA) and biodegradation potential (community metabolism of naphthalene in microcosms) were compared to measurements from 6 years earlier. cDNA sequences amplified from total RNA extracts revealed that nah- and nag-type genes were expressed in situ, corresponding well with structural gene abundances. Despite evidence for short-term (9-month) shifts in dioxygenase gene copy number, agreement in field gene expression (dioxygenase mRNA) and biodegradation potential was observed in comparisons to equivalent assays performed 6 years earlier. Thus, stability in community biodegradation characteristics at the hemidecadal time frame has been documented for these subsurface microbial communities.« less

  6. Analysis of salicylic acid-dependent pathways in Arabidopsis thaliana following infection with Plasmodiophora brassicae and the influence of salicylic acid on disease.

    PubMed

    Lovelock, David A; Šola, Ivana; Marschollek, Sabine; Donald, Caroline E; Rusak, Gordana; van Pée, Karl-Heinz; Ludwig-Müller, Jutta; Cahill, David M

    2016-10-01

    Salicylic acid (SA) biosynthesis, the expression of SA-related genes and the effect of SA on the Arabidopsis-Plasmodiophora brassicae interaction were examined. Biochemical analyses revealed that, in P. brassicae-infected Arabidopsis, the majority of SA is synthesized from chorismate. Real-time monitored expression of a gene for isochorismate synthase was induced on infection. SA can be modified after accumulation, either by methylation, improving its mobility, or by glycosylation, as one possible reaction for inactivation. Quantitative reverse transcription-polymerase chain reaction (qPCR) confirmed the induction of an SA methyltransferase gene, whereas SA glucosyltransferase expression was not changed after infection. Col-0 wild-type (wt) did not provide a visible phenotypic resistance response, whereas the Arabidopsis mutant dnd1, which constitutively activates the immune system, showed reduced gall scores. As dnd1 showed control of the pathogen, exogenous SA was applied to Arabidopsis in order to test whether it could suppress clubroot. In wt, sid2 (SA biosynthesis), NahG (SA-deficient) and npr1 (SA signalling-impaired) mutants, SA treatment did not alter the gall score, but positively affected the shoot weight. This suggests that SA alone is not sufficient for Arabidopsis resistance against P. brassicae. Semi-quantitative PCR revealed that wt, cpr1, dnd1 and sid2 showed elevated PR-1 expression on P. brassicae and SA + P. brassicae inoculation at 2 and 3 weeks post-inoculation (wpi), whereas NahG and npr1 showed no expression. This work contributes to the understanding of SA involvement in the Arabidopsis-P. brassicae interaction. © 2015 BSPP and John Wiley & Sons Ltd.

  7. NHERF2/NHERF3 protein heterodimerization and macrocomplex formation are required for the inhibition of NHE3 activity by carbachol.

    PubMed

    Yang, Jianbo; Singh, Varsha; Chen, Tian-E; Sarker, Rafiquel; Xiong, Lishou; Cha, Boyoung; Jin, Shi; Li, Xuhang; Tse, C Ming; Zachos, Nicholas C; Donowitz, Mark

    2014-07-18

    NHERF1, NHERF2, and NHERF3 belong to the NHERF (Na(+)/H(+) exchanger regulatory factor) family of PSD-95/Discs-large/ZO-1 (PDZ) scaffolding proteins. Individually, each NHERF protein has been shown to be involved in the regulation of multiple receptors or transporters including Na(+)/H(+) exchanger 3 (NHE3). Although NHERF dimerizations have been reported, results have been inconsistent, and the physiological function of NHERF dimerizations is still unknown. The current study semiquantitatively compared the interaction strength among all possible homodimerizations and heterodimerizations of these three NHERF proteins by pulldown and co-immunoprecipitation assays. Both methods showed that NHERF2 and NHERF3 heterodimerize as the strongest interaction among all NHERF dimerizations. In vivo NHERF2/NHERF3 heterodimerization was confirmed by FRET and FRAP (fluorescence recovery after photobleach). NHERF2/NHERF3 heterodimerization is mediated by PDZ domains of NHERF2 and the C-terminal PDZ domain recognition motif of NHERF3. The NHERF3-4A mutant is defective in heterodimerization with NHERF2 and does not support the inhibition of NHE3 by carbachol. This suggests a role for NHERF2/NHERF3 heterodimerization in the regulation of NHE3 activity. In addition, both PDZ domains of NHERF2 could be simultaneously occupied by NHERF3 and another ligand such as NHE3, α-actinin-4, and PKCα, promoting formation of NHE3 macrocomplexes. This study suggests that NHERF2/NHERF3 heterodimerization mediates the formation of NHE3 macrocomplexes, which are required for the inhibition of NHE3 activity by carbachol. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  8. Hydrogen sulfide acts as a downstream signal molecule in salicylic acid-induced heat tolerance in maize (Zea mays L.) seedlings.

    PubMed

    Li, Zhong-Guang; Xie, Lin-Run; Li, Xiao-Juan

    2015-04-01

    Salicylic acid (SA), 2-hydroxy benzoic acid, is a small phenolic compound with multifunction that is involved in plant growth, development, and the acquisition of stress tolerance. In recent years, hydrogen sulfide (H2S) has been found to have similar functions, but cross talk between SA and H2S in the acquisition of heat tolerance is not clear. In this study, pretreatment of maize seedlings with SA improved the survival percentage of seedlings under heat stress, indicating that SA pretreatment could improve the heat tolerance of maize seedlings. In addition, treatment with SA enhanced the activity of L-cysteine desulfhydrase (L-DES), a key enzyme in H2S biosynthesis, which in turn induced accumulation of endogenous H2S. Interestingly, SA-induced heat tolerance was enhanced by addition of NaHS, a H2S donor, but weakened by specific inhibitors of H2S biosynthesis DL-propargylglycine (PAG) and its scavenger hydroxylamine (HT). Furthermore, pretreatment with paclobutrazol (PAC) and 2-aminoindan-2-phosphonic acid (AIP), inhibitors of SA biosynthesis, had no significant effect on NaHS-induced heat tolerance of maize seedlings. Similarly, significant change in the activities of phenylalanine ammonia lyase (PAL) and benzoic-acid-2-hydroxylase (BA2H), the key enzymes in SA biosynthesis, and the content of endogenous SA, was not observed in maize seedlings by NaHS treatment. All of the above-mentioned results suggest that SA pretreatment could improve the heat tolerance of maize seedlings, and H2S might be a novel downstream signal molecule in SA-induced heat tolerance. Copyright © 2015 Elsevier GmbH. All rights reserved.

  9. Hydrogen Sulfide Ameliorates Homocysteine-Induced Cognitive Dysfunction by Inhibition of Reactive Aldehydes Involving Upregulation of ALDH2.

    PubMed

    Li, Min; Zhang, Ping; Wei, Hai-Jun; Li, Man-Hong; Zou, Wei; Li, Xiang; Gu, Hong-Feng; Tang, Xiao-Qing

    2017-04-01

    Homocysteine, a risk factor for Alzheimer's disease, induces cognitive dysfunction. Reactive aldehydes play an important role in cognitive dysfunction. Aldehyde-dehydrogenase 2 detoxifies reactive aldehydes. Hydrogen sulfide, a novel neuromodulator, has neuroprotective effects and regulates learning and memory. Our previous work confirmed that the disturbance of hydrogen sulfide synthesis is invovled in homocysteine-induced defects in learning and memory. Therefore, the present work was to explore whether hydrogen sulfide ameliorates homocysteine-generated cognitive dysfunction and to investigate whether its underlying mechanism is related to attenuating accumulation of reactive aldehydes by upregulation of aldehyde-dehydrogenase 2. The cognitive function of rats was assessed by the Morris water maze test and the novel object recognition test. The levels of malondialdehyde, 4-hydroxynonenal, and glutathione as well as the activity of aldehyde-dehydrogenase 2 were determined by enzyme linked immunosorbent assay; the expression of aldehyde-dehydrogenase 2 was detected by western blot. The behavior experiments, Morris water maze test and novel objects recognition test, showed that homocysteine induced deficiency in learning and memory in rats, and this deficiency was reversed by treatment of NaHS (a donor of hydrogen sulfide). We demonstrated that NaHS inhibited homocysteine-induced increases in generations of MDA and 4-HNE in the hippocampus of rats and that hydrogen sulfide reversed homocysteine-induced decreases in the level of glutathione as well as the activity and expression of aldehyde-dehydrogenase 2 in the hippocampus of rats. Hydrogen sulfide ameliorates homocysteine-induced impairment in cognitive function by decreasing accumulation of reactive aldehydes as a result of upregulations of glutathione and aldehyde-dehydrogenase 2. © The Author 2016. Published by Oxford University Press on behalf of CINP.

  10. Hydrogen Sulfide Ameliorates Homocysteine-Induced Cognitive Dysfunction by Inhibition of Reactive Aldehydes Involving Upregulation of ALDH2

    PubMed Central

    Li, Min; Zhang, Ping; Wei, Hai-jun; Li, Man-Hong; Li, Xiang; Gu, Hong-Feng

    2017-01-01

    Abstract Background: Homocysteine, a risk factor for Alzheimer’s disease, induces cognitive dysfunction. Reactive aldehydes play an important role in cognitive dysfunction. Aldehyde-dehydrogenase 2 detoxifies reactive aldehydes. Hydrogen sulfide, a novel neuromodulator, has neuroprotective effects and regulates learning and memory. Our previous work confirmed that the disturbance of hydrogen sulfide synthesis is invovled in homocysteine-induced defects in learning and memory. Therefore, the present work was to explore whether hydrogen sulfide ameliorates homocysteine-generated cognitive dysfunction and to investigate whether its underlying mechanism is related to attenuating accumulation of reactive aldehydes by upregulation of aldehyde-dehydrogenase 2. Methods: The cognitive function of rats was assessed by the Morris water maze test and the novel object recognition test. The levels of malondialdehyde, 4-hydroxynonenal, and glutathione as well as the activity of aldehyde-dehydrogenase 2 were determined by enzyme linked immunosorbent assay; the expression of aldehyde-dehydrogenase 2 was detected by western blot. Results: The behavior experiments, Morris water maze test and novel objects recognition test, showed that homocysteine induced deficiency in learning and memory in rats, and this deficiency was reversed by treatment of NaHS (a donor of hydrogen sulfide). We demonstrated that NaHS inhibited homocysteine-induced increases in generations of MDA and 4-HNE in the hippocampus of rats and that hydrogen sulfide reversed homocysteine-induced decreases in the level of glutathione as well as the activity and expression of aldehyde-dehydrogenase 2 in the hippocampus of rats. Conclusion: Hydrogen sulfide ameliorates homocysteine-induced impairment in cognitive function by decreasing accumulation of reactive aldehydes as a result of upregulations of glutathione and aldehyde-dehydrogenase 2. PMID:27988490

  11. Lanthanide complexes as luminogenic probes to measure sulfide levels in industrial samples.

    PubMed

    Thorson, Megan K; Ung, Phuc; Leaver, Franklin M; Corbin, Teresa S; Tuck, Kellie L; Graham, Bim; Barrios, Amy M

    2015-10-08

    A series of lanthanide-based, azide-appended complexes were investigated as hydrogen sulfide-sensitive probes. Europium complex 1 and Tb complex 3 both displayed a sulfide-dependent increase in luminescence, while Tb complex 2 displayed a decrease in luminescence upon exposure to NaHS. The utility of the complexes for monitoring sulfide levels in industrial oil and water samples was investigated. Complex 3 provided a sensitive measure of sulfide levels in petrochemical water samples (detection limit ∼ 250 nM), while complex 1 was capable of monitoring μM levels of sulfide in partially refined crude oil. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Acidification of the gill cells of the shore crab Carcinus mediterraneus: Its physiological significance

    NASA Astrophysics Data System (ADS)

    Lucu, Č.; Siebers, D.

    1995-03-01

    In a preparation of isolated gills of the shore crab Carcinus mediterraneus perfused with dilute sea water (pH 8.1, 200 mM Na+) which was identical to the bathing solution of the gill, acidification of the collected perfusate was observed. Acidification was not affected by 10-4 M EIPA (5-[N-ethyl-N-isopropyl]amiloride), a strong inhibitor of Na+/H+ exchange. However, in the presence of 10-4 M acetazolamide, acidification was greatly blocked. The significant decrease of the acid load of the perfusate is considered to be a result of inhibition of the branchial intracellular carbonic anhydrase catalyzing the formation of H+ ions.

  13. Autoradiography and Immunofluorescence Combined for Autecological Study of Single Cell Activity with Nitrobacter as a Model System1

    PubMed Central

    Fliermans, C. B.; Schmidt, E. L.

    1975-01-01

    Specific detection of a particular bacterium by immunofluorescence was combined with estimation of its metabolic activity by autoradiography. The nitrifying bacteria Nitrobacter agilis and N. winogradskyi were used as a model system. Nitrobacter were incubated with NaH14CO3 and 14CO2 prior to study. The same preparations made for autoradiograms were stained with fluorescent antibodies specific for the Nitrobacter species. Examination by epifluorescence and transmitted dark-field microscopy revealed Nitrobacter cells with and without associated silver grains. Direct detection and simultaneous evaluation of metabolic activity of Nitrobacter was demonstrated in pure cultures, in a simple mixed culture, and in a natural soil. Images PMID:1103733

  14. Enhanced mechanical properties and increased corrosion resistance of a biodegradable magnesium alloy by plasma electrolytic oxidation (PEO).

    PubMed

    White, Leon; Koo, Youngmi; Neralla, Sudheer; Sankar, Jagannathan; Yun, Yeoheung

    2016-06-01

    We report the enhanced mechanical properties of AZ31 magnesium alloys by plasma electrolytic oxidation (PEO) coating in NaOH, Na 2 SiO 3 , KF and NaH 2 PO 4 ·2H 2 O containing electrolytes. Mechanical properties including wear resistance, surface hardness and elastic modulus were increased for PEO-coated AZ31 Mg alloys (PEO-AZ31). DC polarization in Hank's solution indicating that the corrosion resistance significantly increased for PEO-coating in KF-contained electrolyte. Based on these results, the PEO coating method shows promising potential for use in biodegradable implant applications where tunable corrosion and mechanical properties are needed.

  15. Sequence specificity of the hammerhead ribozyme revisited; the NHH rule.

    PubMed Central

    Kore, A R; Vaish, N K; Kutzke, U; Eckstein, F

    1998-01-01

    The sequence specificity of hammerhead ribozyme cleavage has been re-evaluated with respect to the NUH rule. Contrary to previous reports it was found that substrates with GAC triplets were also cleaved. This was established in three different sequence contexts. The rate of cleavage under single turnover conditions was between 3 and 7% that of cleavage 3' of GUC. Specificity of cleavage of substrates containing a central A in the cleavable triplet can be described as NAH, where N can be any nucleotide and H any nucleotide but G. As cleavage 3' of NCH triplets has recently been described, the NUH rule can be reformulated to NHH. PMID:9722629

  16. Alternative analytical forms to model diatomic systems based on the deformed exponential function.

    PubMed

    da Fonsêca, José Erinaldo; de Oliveira, Heibbe Cristhian B; da Cunha, Wiliam Ferreira; Gargano, Ricardo

    2014-07-01

    Using a deformed exponential function and the molecular-orbital theory for the simplest molecular ion, two new analytical functions are proposed to represent the potential energy of ground-state diatomic systems. The quality of these new forms was tested by fitting the ab initio electronic energies of the system LiH, LiNa, NaH, RbH, KH, H2, Li2, K2, H 2 (+) , BeH(+) and Li 2 (+) . From these fits, it was verified that these new proposals are able to adequately describe homonuclear, heteronuclear and cationic diatomic systems with good accuracy. Vibrational spectroscopic constant results obtained from these two proposals are in good agreement with experimental data.

  17. Kompressionstherapie bei Patienten mit Ulcus cruris venosum.

    PubMed

    Dissemond, Joachim; Assenheimer, Bernd; Bültemann, Anke; Gerber, Veronika; Gretener, Silvia; Kohler-von Siebenthal, Elisabeth; Koller, Sonja; Kröger, Knut; Kurz, Peter; Läuchli, Severin; Münter, Christian; Panfil, Eva-Maria; Probst, Sebastian; Protz, Kerstin; Riepe, Gunnar; Strohal, Robert; Traber, Jürg; Partsch, Hugo

    2016-11-01

    Wund-D.A.CH. ist der Dachverband deutschsprachiger Fachgesellschaften, die sich mit den Thematiken der Wundbehandlung beschäftigen. Experten verschiedener Fachgesellschaften aus Deutschland, Österreich und der Schweiz haben nun einen aktuellen Konsens der Kompressionstherapie für Patienten mit Ulcus cruris venosum erstellt. In Europa ist das Ulcus cruris venosum eine der häufigsten Ursachen für chronische Wunden. Neben der konservativen und interventionellen Wund- und Venentherapie, ist die Kompressionstherapie die Basis der Behandlungsstrategien. Die Kompressionstherapie kann heute mit sehr unterschiedlichen Materialien und Systemen durchgeführt werden. Während in der Entstauungsphase insbesondere Verbände mit Kurzzugbinden oder Mehrkomponentensysteme zur Anwendung kommen, sind es anschließend überwiegend Ulkus-Strumpfsysteme. Eine weitere, bislang wenig verbreitete Alternative sind adaptive Kompressionsbandagen. Insbesondere für die Rezidivprophylaxe werden medizinische Kompressionsstrümpfe empfohlen. Durch die Vielzahl der heute zur Verfügung stehenden Behandlungsoptionen, kann für nahezu alle Patienten ein Konzept entwickelt werden, dass sich an den individuellen Bedürfnissen und Fähigkeiten orientiert und daher auch akzeptiert und durchgeführt wird. Die Kompressionstherapie ist für die Behandlung von Patienten mit Ulcus cruris venosum essentiell. In den letzten Jahren sind viele verschiedene Therapieoptionen verfügbar, die in den deutschsprachigen Ländern unterschiedlich angewendet oder durchgeführt werden. Daher soll dieser Expertenkonsens dazu beitragen, konkrete Empfehlungen für die praktische Durchführung der Kompressionstherapie von Patienten mit Ulcus cruris venosum darzustellen. © 2016 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

  18. Krankheitsverlauf, medizinische Versorgung und Lebensqualität von Patienten mit kongenitalen melanozytären Nävi - Auswertung des deutschsprachigen KMN-Registers.

    PubMed

    Elisabeth Wramp, Maria; Langenbruch, Anna; Augustin, Matthias; Zillikens, Detlef; Krengel, Sven

    2017-02-01

    Kongenitale melanozytäre Nävi (KMN) bedeuten für Patienten und Familien eine psychologische Belastung und bergen zudem medizinische Risiken. Das 2005 gegründete deutschsprachige KMN-Register wurde nun einer Zwischenauswertung bezüglich des Krankheitsverlaufes, der medizinischen Versorgung und der Lebensqualität unterzogen. 100 Patienten, die sich in den Jahren 2005 bis 2012 mit einem Erstmeldebogen registriert hatten, wurde im Rahmen einer prospektiven Kohortenstudie Anfang 2013 ein Folgemeldebogen zugesandt. Außerdem wurden mithilfe standardisierter Fragebögen Daten zu Lebensqualität (dermatology life quality index, DLQI) und Stigmatisierungserfahrungen (perceived stigmatization questionnaire, PSQ; social comfort questionnaire, SCQ) erhoben. 83 % der Patienten oder deren Eltern antworteten (Altersdurchschnitt 11,2 Jahre, Median 6 Jahre; mittleres Follow-up 4,4 Jahre). Im Gesamtkollektiv wurden vier Melanome diagnostiziert, davon zwei zerebrale Melanome im Kindesalter, ein kutanes Melanom im Erwachsenenalter und eines, das sich als proliferierender Knoten erwies. Bei vier Kindern wurde eine neurokutane Melanozytose festgestellt, drei davon mit neurologischer Symptomatik. Chirurgisch behandelt wurden 88 % (73/83). Achtundsiebzig Prozent der Befragten berichteten eine geringe oder keine Beeinträchtigung der Lebensqualität. Die wahrgenommene Stigmatisierung beziehungsweise Beeinträchtigung des sozialen Wohlbefindens war generell ebenfalls gering. Die Ergebnisse geben einen Überblick über die Situation von Patienten mit KMN in Deutschland, Österreich und der Schweiz. Ein Melanom entwickelte sich in 3 %, eine ZNS-Beteiligung bestand in 4 % der Fälle. © 2017 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

  19. B-Zell-Lymphome der Haut - Pathogenese, Diagnostik und Therapie.

    PubMed

    Nicolay, Jan P; Wobser, Marion

    2016-12-01

    Primär kutane B-Zell-Lymphome (PCBCL) beschreiben reifzellige lymphoproliferative Erkrankungen der B-Zell-Reihe, die primär die Haut betreffen. Die Biologie und der klinische Verlauf der einzelnen PCBCL-Subtypen variieren untereinander stark und unterscheiden sich grundsätzlich von primär nodalen und systemischen B-Zell-Lymphomen. Primär kutane Marginalzonenlymphome (PCMZL) und primäre kutane follikuläre Keimzentrumslymphome (PCFCL) werden auf Grund ihres unkomplizierten Verlaufs und ihrer exzellenten Prognose zu den indolenten PCBCL gezählt. Demgegenüber stellen die diffus großzelligen B-Zell-Lymphome, hauptsächlich vom Beintyp (DLBCL, LT) die aggressiveren PCBCL-Varianten mit schlechterer Prognose dar. Für die Ausbreitungsdiagnostik und die Therapieentscheidung sind eine genaue histologische und immunhistochemische Klassifizierung sowie der Ausschluss einer systemischen Beteiligung in Abgrenzung zu nodalen oder systemischen Lymphomen notwendig. Die Diagnostik sollte dabei durch molekularbiologische Untersuchungen unterstützt werden. Therapeutisch stehen für die indolenten PCBCL primär operative und radioonkologische Maßnahmen im Vordergrund sowie eine Systemtherapie mit dem CD20-Antikörper Rituximab bei disseminiertem Befall. Die aggressiveren Varianten sollten in erster Linie mit Kombinationen aus Rituximab und Polychemotherapieschemata wie z. B. dem CHOP-Schema oder Modifikationen davon behandelt werden. Auf Grund der in allen seinen Einzelheiten noch nicht vollständig verstandenen Pathogenese und Biologie sowie des begrenzten Therapiespektrums der PCBCL besteht hier, speziell beim DLBCL, LT, noch erheblicher Forschungsbedarf. © 2016 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

  20. Uncommon pollen walls: reasons and consequences*)

    PubMed Central

    Pacini, Ettore; Hesse, Michael

    2016-01-01

    The mature pollen wall of gymnosperms and angiosperms consists in principle of two fundamentally different layers, the complex, thick sporopolleninous exine and the homogeneous, thin, single-layered pectocellulosic intine. In angiosperms, the typical exine is usually formed by a tectum, columellae, a foot layer, and an endexine. An exine reduction (minimally up to the complete absence) occurs in many unrelated seed plants, without consequences for pollen viability. The intine sometimes also deviates from its common form, being either extremely thick or appearing two- or even three-layered. Environmental factors or developmental constraints are highlighted as being responsible for the various deviating exine and intine forms. Pacini E. & Hesse M, 2012: Unkomplette Pollenwand – Gründe und Konsequenzen Die fertige Pollenwand der Gymnospermen und der Angiospermen besteht im Prinzip aus zwei fundamental verschiedenen Lagen, aus der komplexen, dicken und sporopolleninhältigen Exine, und der homogenen, dünnen, einschichtigen und überwiegend zellulosehältigen Intine. Bei Angiospermen ist die typische Exine aus einem Tectum, aus Columellae, aus einem Foot Layer und zumeist noch aus einer Endexine geformt. In vielen, nicht miteinander verwandten Angiospermen (seltener bei Gymnospermen) is die Exine mehr oder weniger stark reduziert, was allerdings keinen Einfluß auf die Keimungsfähigkeit des Pollens hat. Auch die Intine weicht manchmal von ihrer üblichen Ausbildung ab, ist entweder auffallend dick oder zwei bis dreischichtig. Sowohl Umweltfaktoren als auch embryologisch und entwicklungsgeschichtlich bedingte Hemmungen sind für die abweichenden Exine- und Intineformen verantwortlich. PMID:28904424