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Sample records for glutamate pool sizes

  1. Characterization of depolarization-coupled release of glutamate from cultured mouse cerebellar granule cells using DL-threo-beta-benzyloxyaspartate (DL-TBOA) to distinguish between the vesicular and cytoplasmic pools

    DEFF Research Database (Denmark)

    Bak, Lasse K; Schousboe, Arne; Waagepetersen, Helle S

    2003-01-01

    Release of preloaded [3H]D-aspartate in response to depolarization induced by N-methyl-D-aspartate (NMDA) or the endogenous agonist glutamate was characterized using cultured glutamatergic cerebellar granule neurons. Release from the vesicular and the cytoplasmic glutamate pools, respectively, wa...

  2. Rapid synthesis and metabolism of glutamate in N2-fixing bacteroids

    International Nuclear Information System (INIS)

    Salminen, S.O.; Streeter, J.G.

    1987-01-01

    Symbiotic nodule bacteroids are thought to support N 2 fixation mainly by metabolizing dicarboxylic acids to CO 2 , generating reductant and ATP required by nitrogenase. Bradyrhizobium japonicum bacteroids were isolated anaerobically and incubated at 2% O 2 with 14 C-labeled succinate, malate, glutamate, or aspartate. 14 CO 2 was collected, and the bacteroid contents separated into neutral, organic acid, and amino acid fractions. The respiration of substrates, relative to their uptake, was malate > glutamate > succinate > aspartate. Analysis of the fractions revealed that will all substrates the radioactivity was found mostly in the amino acid fraction. The labeling of the neutral fraction was negligible and only a small amount of label was found in the organic acid fraction indicating a small pool size. TLC of the amino acid fraction showed the label to be principally in glutamate. Glutamate contained 67, 80, 97, and 88% of the 14 C in the amino acid fraction in bacteroids fed with succinate, malate, glutamate and aspartate, respectively. The data suggest that glutamate may play an important role in the bacteroid function

  3. Introduction to the Glutamate-Glutamine Cycle

    DEFF Research Database (Denmark)

    Sonnewald, Ursula; Schousboe, Arne

    2016-01-01

    . This is metabolically impossible unless it is assumed that at least two distinct pools of these amino acids exist. This combined with the finding that the enzyme synthesizing glutamine from glutamate was expressed in astrocytes but not in neurons formed the basis of the notion that a cycle must exist in which glutamate......The term 'glutamate-glutamine cycle' was coined several decades ago based on the observation that using certain (14)C-labeled precursors for studies of brain metabolism the specific radioactivity of glutamine generated from glutamate was higher than that of glutamate, its immediate precursor...... released from neurons is transported into astrocytes, converted to glutamine which is subsequently returned to neurons and converted to glutamate by an enzyme the activity of which is much higher in neurons than in astrocytes. Originally this cycle was supposed to function in a stoichiometric fashion...

  4. Introduction to the Glutamate-Glutamine Cycle

    DEFF Research Database (Denmark)

    Sonnewald, Ursula; Schousboe, Arne

    2016-01-01

    released from neurons is transported into astrocytes, converted to glutamine which is subsequently returned to neurons and converted to glutamate by an enzyme the activity of which is much higher in neurons than in astrocytes. Originally this cycle was supposed to function in a stoichiometric fashion......The term 'glutamate-glutamine cycle' was coined several decades ago based on the observation that using certain (14)C-labeled precursors for studies of brain metabolism the specific radioactivity of glutamine generated from glutamate was higher than that of glutamate, its immediate precursor....... This is metabolically impossible unless it is assumed that at least two distinct pools of these amino acids exist. This combined with the finding that the enzyme synthesizing glutamine from glutamate was expressed in astrocytes but not in neurons formed the basis of the notion that a cycle must exist in which glutamate...

  5. Gravity and Heater Size Effects on Pool Boiling Heat Transfer

    Science.gov (United States)

    Kim, Jungho; Raj, Rishi

    2014-01-01

    The current work is based on observations of boiling heat transfer over a continuous range of gravity levels between 0g to 1.8g and varying heater sizes with a fluorinert as the test liquid (FC-72/n-perfluorohexane). Variable gravity pool boiling heat transfer measurements over a wide range of gravity levels were made during parabolic flight campaigns as well as onboard the International Space Station. For large heaters and-or higher gravity conditions, buoyancy dominated boiling and heat transfer results were heater size independent. The power law coefficient for gravity in the heat transfer equation was found to be a function of wall temperature under these conditions. Under low gravity conditions and-or for smaller heaters, surface tension forces dominated and heat transfer results were heater size dependent. A pool boiling regime map differentiating buoyancy and surface tension dominated regimes was developed along with a unified framework that allowed for scaling of pool boiling over a wide range of gravity levels and heater sizes. The scaling laws developed in this study are expected to allow performance quantification of phase change based technologies under variable gravity environments eventually leading to their implementation in space based applications.

  6. Evaluation of Decontamination Factor of Aerosol in Pool Scrubber according to Bubble Shape and Size

    Energy Technology Data Exchange (ETDEWEB)

    Jo, Hyun Joung; Ha, Kwang Soon; Jang, Dong Soon [KAERI, Daejeon (Korea, Republic of)

    2016-05-15

    The scrubbing pool could play an important role in the wet type FCVS because a large amount of aerosol is captured in the water pool. The pool scrubbing phenomena have been modelled and embedded in several computer codes, such as SPARC (Suppression Pool Aerosol Removal Code), BUSCA (BUbble Scrubbing Algorithm) and SUPRA (Suppression Pool Retention Analysis). These codes aim at simulating the pool scrubbing process and estimating the decontamination factors (DFs) of the radioactive aerosol and iodine gas in the water pool, which is defined as the ratio of initial mass of the specific radioactive material to final massy after passing through the water pool. The pool scrubbing models were reviewed and an aerosol scrubbing code has been prepared to calculate decontamination factor through the pool. The developed code has been verified using the experimental results and parametric studies the decontamination factor according to bubble shape and size. To evaluate the decontamination factor more accurate whole pool scrubber phenomena, the code was improved to consider the variety shape and size of bubbles. The decontamination factor were largely evaluated in ellipsoid bubble rather than in sphere bubble. The pool scrubbing models will be enhanced to apply more various model such as aerosol condensation of hygroscopic. And, it is need to experiment to measure to bubble shape and size distribution in pool to improve bubble model.

  7. Controls on the size and occurrence of pools in coarse-grained forest rivers

    Science.gov (United States)

    John M. Buffington; Thomas E. Lisle; Richard D. Woodsmith; Sue Hilton

    2002-01-01

    Controls on pool formation are examined in gravel- and cobble-bed rivers in forest mountain drainage basins of northern California, southern Oregon, and southeastern Alaska. We demonstrate that the majority of pools at our study sites are formed by flow obstructions and that pool geometry and frequency largely depend on obstruction characteristics (size, type, and...

  8. Laser-scanning astrocyte mapping reveals increased glutamate-responsive domain size and disrupted maturation of glutamate uptake following neonatal cortical freeze-lesion

    Directory of Open Access Journals (Sweden)

    Mortiz eArmbruster

    2014-09-01

    Full Text Available Astrocytic uptake of glutamate shapes extracellular neurotransmitter dynamics, receptor activation, and synaptogenesis. During development, glutamate transport becomes more robust. How neonatal brain insult affects the functional maturation of glutamate transport remains unanswered. Neonatal brain insult can lead to developmental delays, cognitive losses, and epilepsy; the disruption of glutamate transport is known to cause changes in synaptogenesis, receptor activation, and seizure. Using the neonatal freeze-lesion (FL model, we have investigated how insult affects the maturation of astrocytic glutamate transport. As lesioning occurs on the day of birth, a time when astrocytes are still functionally immature, this model is ideal for identifying changes in astrocyte maturation following insult. Reactive astrocytosis, astrocyte proliferation, and in vitro hyperexcitability are known to occur in this model. To probe astrocyte glutamate transport with better spatial precision we have developed a novel technique, Laser Scanning Astrocyte Mapping (LSAM, which combines glutamate transport current (TC recording from astrocytes with laser scanning glutamate photolysis. LSAM allows us to identify the area from which a single astrocyte can transport glutamate and to quantify spatial heterogeneity in the rate of glutamate clearance kinetics within that domain. Using LSAM, we report that cortical astrocytes have an increased glutamate-responsive area following FL and that TCs have faster decay times in distal, as compared to proximal processes. Furthermore, the developmental shift from GLAST- to GLT-1-dominated clearance is disrupted following FL. These findings introduce a novel method to probe astrocyte glutamate uptake and show that neonatal cortical FL disrupts the functional maturation of cortical astrocytes.

  9. Project size and common pool size: An empirical test using Danish municipal mergers

    DEFF Research Database (Denmark)

    Hansen, Sune Welling

    The paper examines the proposition that project size tends to increase with common pool size from the law of 1 over n (Weingast et al, 1981). This remains under-investigated and a recent study conducted by Primo & Snyder (2008) argues, and empirically substantiates, a reverse law of 1 over n...... across two research designs, two outcome variables, two subsamples, and several model specifications The implications of the findings, combined with the limited potential for empirically testing Primo & Snyder’s alternative model, suggest a re-appreciation of the law of 1 over n as it was originally...

  10. Role of aminotransferases in glutamate metabolism of human erythrocytes

    Energy Technology Data Exchange (ETDEWEB)

    Ellinger, James J. [University of Wisconsin-Madison, Department of Biochemistry (United States); Lewis, Ian A. [Princeton University, Lewis-Sigler Institute for Integrative Genomics (United States); Markley, John L., E-mail: markley@nmrfam.wisc.edu [University of Wisconsin-Madison, Department of Biochemistry (United States)

    2011-04-15

    Human erythrocytes require a continual supply of glutamate to support glutathione synthesis, but are unable to transport this amino acid across their cell membrane. Consequently, erythrocytes rely on de novo glutamate biosynthesis from {alpha}-ketoglutarate and glutamine to maintain intracellular levels of glutamate. Erythrocytic glutamate biosynthesis is catalyzed by three enzymes, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and glutamine aminohydrolase (GA). Although the presence of these enzymes in RBCs has been well documented, the relative contributions of each pathway have not been established. Understanding the relative contributions of each biosynthetic pathway is critical for designing effective therapies for sickle cell disease, hemolytic anemia, pulmonary hypertension, and other glutathione-related disorders. In this study, we use multidimensional {sup 1}H-{sup 13}C nuclear magnetic resonance (NMR) spectroscopy and multiple reaction mode mass spectrometry (MRM-MS) to measure the kinetics of de novo glutamate biosynthesis via AST, ALT, and GA in intact cells and RBC lysates. We show that up to 89% of the erythrocyte glutamate pool can be derived from ALT and that ALT-derived glutamate is subsequently used for glutathione synthesis.

  11. Lin28a regulates germ cell pool size and fertility

    Science.gov (United States)

    Shinoda, Gen; de Soysa, T. Yvanka; Seligson, Marc T.; Yabuuchi, Akiko; Fujiwara, Yuko; Huang, Pei Yi; Hagan, John P.; Gregory, Richard I.; Moss, Eric G.; Daley, George Q.

    2013-01-01

    Overexpression of LIN28A is associated with human germ cell tumors and promotes primordial germ cell (PGC) development from embryonic stem cells in vitro and in chimeric mice. Knockdown of Lin28a inhibits PGC development in vitro, but how constitutional Lin28a deficiency affects the mammalian reproductive system in vivo remains unknown. Here, we generated Lin28a knockout (KO) mice and found that Lin28a deficiency compromises the size of the germ cell pool in both males and females by affecting PGC proliferation during embryogenesis. Interestingly however, in Lin28a KO males the germ cell pool partially recovers during postnatal expansion, while fertility remains impaired in both males and females mated to wild type mice. Embryonic overexpression of let-7, a microRNA negatively regulated by Lin28a, reduces the germ cell pool, corroborating the role of the Lin28a/let-7 axis in regulating the germ lineage. PMID:23378032

  12. Introduction to the Glutamate-Glutamine Cycle.

    Science.gov (United States)

    Sonnewald, Ursula; Schousboe, Arne

    2016-01-01

    The term 'glutamate-glutamine cycle' was coined several decades ago based on the observation that using certain 14 C-labeled precursors for studies of brain metabolism the specific radioactivity of glutamine generated from glutamate was higher than that of glutamate, its immediate precursor. This is metabolically impossible unless it is assumed that at least two distinct pools of these amino acids exist. This combined with the finding that the enzyme synthesizing glutamine from glutamate was expressed in astrocytes but not in neurons formed the basis of the notion that a cycle must exist in which glutamate released from neurons is transported into astrocytes, converted to glutamine which is subsequently returned to neurons and converted to glutamate by an enzyme the activity of which is much higher in neurons than in astrocytes. Originally this cycle was supposed to function in a stoichiometric fashion but more recent research has seriously questioned this.This volume of Advances in Neurobiology is intended to provide a detailed discussion of recent developments in research aimed at delineating the functional roles of the cycle taking into account that in order for this system to work there must be a tight coupling between metabolism of glutamate in astrocytes, transfer of glutamine to neurons and de novo synthesis of glutamine in astrocytes. To understand this, knowledge about the activity and regulation of the enzymes and transporters involved in these processes is required and as can be seen from the table of contents these issues will be dealt with in detail in the individual chapters of the book.

  13. Influence of the glutamic acid content of the diet on the catabolic rate of labelled glutamic acid in rats. 3

    International Nuclear Information System (INIS)

    Simon, O.; Wilke, A.; Bergner, H.

    1984-01-01

    Mal rats received during a 8 days experimental feeding period diets with different contents in glutamic acid. The daily feed intake was restricted to the energy maintenance level of 460 kJ/kg/sup 0.75/. The diet contained a mixture of L-amino acids corresponding to the pattern of egg protein except glutamic acid. Glutamic acid was added successively at 10 levels (0 to 14.8 % of dry matter) and the resulting diets were fed to groups of 4 animals each. At the end of the experimental feeding period 14 C- and 15 N-labelled glutamic acid were applied by intragastric infusion. CO 2 and 14 CO 2 excretion was measured during the following 4 hours and the urinary N and 15 N excretion during the following 24 hours. The CO 2 excretion decreased from 53 to 44 mmol CO 2 /100g body weight with increasing levels of dietary glutamic acid. This change seems to result from the increasing proportion of amino acids as an energetic fuel. While the amount of oxidized glutamic acid increased with increasing supplements of glutamic acid the relative 14 CO 2 excretion decreased from 57 to 48 % of the applied radioactivity. The urinary 15 N excretion during 24 hours was 31 % of the given amount of 15 N if no glutamic acid was included in the diet. This proportion increased successively up to 52 % in the case of the highest supply of glutamic acid. Because the total N excretion increased at the same extent as the 15 N excretion a complete mixing of the NH 2 groups resulting from glutamic acid due to desamination with the ammonia pool was assumed. No correlation between glutamic acid content of the diet and specific radioactivity of CO 2 or atom-% 15 N excess of urinary N was observed. (author)

  14. Pool size measurements facilitate the determination of fluxes at branching points in nonstationary metabolic flux analysis: The case of Arabidopsis thaliana

    Directory of Open Access Journals (Sweden)

    Robert eHeise

    2015-06-01

    Full Text Available Pool size measurements are important for the estimation of absolute intracellular fluxes in particular scenarios based on data from heavy carbon isotope experiments. Recently, steady-state fluxes estimates were obtained for central carbon metabolism in an intact illuminated rosette of Arabidopsis thaliana grown photoautotrophically (Szecowka et al., 2013; Heise et al., 2014. Fluxes were estimated therein by integrating mass-spectrometric data of the dynamics of the unlabeled metabolic fraction, data on metabolic pool sizes, partitioning of metabolic pools between cellular compartments and estimates of photosynthetically inactive pools, with a simplified model of plant central carbon metabolism. However, the fluxes were determined by treating the pool sizes as fixed parameters. Here we investigated whether and, if so, to what extent the treatment of pool sizes as parameters to be optimized in three scenarios may affect the flux estimates. The results are discussed in terms of benchmark values for canonical pathways and reactions, including starch and sucrose synthesis as well as the ribulose-1,5-bisphosphate carboxylation and oxygenation reactions. In addition, we discuss pathways emerging from a divergent branch point for which pool sizes are required for flux estimation, irrespective of the computational approach used for the simulation of the observable labelling pattern. Therefore, our findings indicate the necessity for development of techniques for accurate pool size measurements to improve the quality of flux estimates from nonstationary flux estimates in intact plant cells in the absence of alternative flux measurements.

  15. Melt-Pool Temperature and Size Measurement During Direct Laser Sintering

    Energy Technology Data Exchange (ETDEWEB)

    List, III, Frederick Alyious [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Dinwiddie, Ralph Barton [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Carver, Keith [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Gockel, Joy E. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2017-08-01

    Additive manufacturing has demonstrated the ability to fabricate complex geometries and components not possible with conventional casting and machining. In many cases, industry has demonstrated the ability to fabricate complex geometries with improved efficiency and performance. However, qualification and certification of processes is challenging, leaving companies to focus on certification of material though design allowable based approaches. This significantly reduces the business case for additive manufacturing. Therefore, real time monitoring of the melt pool can be used to detect the development of flaws, such as porosity or un-sintered powder and aid in the certification process. Characteristics of the melt pool in the Direct Laser Sintering (DLS) process is also of great interest to modelers who are developing simulation models needed to improve and perfect the DLS process. Such models could provide a means to rapidly develop the optimum processing parameters for new alloy powders and optimize processing parameters for specific part geometries. Stratonics’ ThermaViz system will be integrated with the Renishaw DLS system in order to demonstrate its ability to measure melt pool size, shape and temperature. These results will be compared with data from an existing IR camera to determine the best approach for the determination of these critical parameters.

  16. Relative estimates of TCA cycle pool size from 14CO2 production profiles

    International Nuclear Information System (INIS)

    Kelleher, J.K.; Cesta, M.L.; Holleran, A.L.

    1986-01-01

    In metabolic and isotopic steady state, the rate of 14 CO 2 production by TCA cycle intermediates labeled at different positions is linear. However, before the system reaches isotopic steady state, the rate of 14 CO 2 production is non-linear. The x-intercept extrapolated from the linear phase indicates the turnover rate of all metabolic pools the tracer must pass through. By exposing identical systems to 14 C succinate labeled in different positions, the contribution of TCA cycle pools to the non-linear phase may be considered. Specifically, the extrapolated x-intercept for [2,3 14 C] succinate will be greater than the x-intercept for [1,4 14 C] succinate if the TCA cycle pools are a contributing factor to the non-linear phase. The authors have used this method to analyze pyruvate oxidation in AS 30D hepatoma cells. They found that the extrapolated x-intercepts for the two tracers were identical. This indicates that the non-linear phase resulted from equilibration of the tracer with pools prior to entering the TCA cycle, i.e. lactate. Using this technique, it may be possible to estimate the variations in TCA cycle pool sizes in vivo

  17. Analysis of small sample size studies using nonparametric bootstrap test with pooled resampling method.

    Science.gov (United States)

    Dwivedi, Alok Kumar; Mallawaarachchi, Indika; Alvarado, Luis A

    2017-06-30

    Experimental studies in biomedical research frequently pose analytical problems related to small sample size. In such studies, there are conflicting findings regarding the choice of parametric and nonparametric analysis, especially with non-normal data. In such instances, some methodologists questioned the validity of parametric tests and suggested nonparametric tests. In contrast, other methodologists found nonparametric tests to be too conservative and less powerful and thus preferred using parametric tests. Some researchers have recommended using a bootstrap test; however, this method also has small sample size limitation. We used a pooled method in nonparametric bootstrap test that may overcome the problem related with small samples in hypothesis testing. The present study compared nonparametric bootstrap test with pooled resampling method corresponding to parametric, nonparametric, and permutation tests through extensive simulations under various conditions and using real data examples. The nonparametric pooled bootstrap t-test provided equal or greater power for comparing two means as compared with unpaired t-test, Welch t-test, Wilcoxon rank sum test, and permutation test while maintaining type I error probability for any conditions except for Cauchy and extreme variable lognormal distributions. In such cases, we suggest using an exact Wilcoxon rank sum test. Nonparametric bootstrap paired t-test also provided better performance than other alternatives. Nonparametric bootstrap test provided benefit over exact Kruskal-Wallis test. We suggest using nonparametric bootstrap test with pooled resampling method for comparing paired or unpaired means and for validating the one way analysis of variance test results for non-normal data in small sample size studies. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  18. Astrocytic control of biosynthesis and turnover of the neurotransmitters glutamate and GABA

    DEFF Research Database (Denmark)

    Schousboe, Arne; Bak, Lasse Kristoffer; Waagepetersen, Helle S

    2013-01-01

    Glutamate and GABA are the quantitatively major neurotransmitters in the brain mediating excitatory and inhibitory signaling, respectively. These amino acids are metabolically interrelated and at the same time they are tightly coupled to the intermediary metabolism including energy homeostasis....... Astrocytes play a pivotal role in the maintenance of the neurotransmitter pools of glutamate and GABA since only these cells express pyruvate carboxylase, the enzyme required for de novo synthesis of the two amino acids. Such de novo synthesis is obligatory to compensate for catabolism of glutamate and GABA...... related to oxidative metabolism when the amino acids are used as energy substrates. This, in turn, is influenced by the extent to which the cycling of the amino acids between neurons and astrocytes may occur. This cycling is brought about by the glutamate/GABA - glutamine cycle the operation of which...

  19. Optimization of the LENS process for steady molten pool size

    Energy Technology Data Exchange (ETDEWEB)

    Wang, L. [Center for Advanced Vehicular Systems, Mississippi State University, Mississippi State, MS 39762 (United States); Felicelli, S. [Mechanical Engineering Department, Mississippi State University, Mississippi State, MS 39762 (United States)], E-mail: felicelli@me.msstate.edu; Gooroochurn, Y. [ESI Group, Bloomfield Hills, MI 48304 (United States); Wang, P.T.; Horstemeyer, M.F. [Center for Advanced Vehicular Systems, Mississippi State University, Mississippi State, MS 39762 (United States)

    2008-02-15

    A three-dimensional finite element model was developed and applied to analyze the temperature and phase evolution in deposited stainless steel 410 (SS410) during the Laser Engineered Net Shaping (LENS) rapid fabrication process. The effect of solid phase transformations is taken into account by using temperature and phase dependent material properties and the continuous cooling transformation (CCT) diagram. The laser beam is modeled as a Gaussian distribution of heat flux from a moving heat source with conical shape. The laser power and translational speed during deposition of a single-wall plate are optimized in order to maintain a steady molten pool size. It is found that, after an initial transient due to the cold substrate, the dependency of laser power with layer number is approximately linear for all travel speeds analyzed. The temperature distribution and cooling rate surrounding the molten pool are predicted and compared with experiments. Based upon the predicted thermal cycles and cooling rate, the phase transformations and their effects on the hardness of the part are discussed.

  20. Metabolic control of vesicular glutamate transport and release.

    Science.gov (United States)

    Juge, Narinobu; Gray, John A; Omote, Hiroshi; Miyaji, Takaaki; Inoue, Tsuyoshi; Hara, Chiaki; Uneyama, Hisayuki; Edwards, Robert H; Nicoll, Roger A; Moriyama, Yoshinori

    2010-10-06

    Fasting has been used to control epilepsy since antiquity, but the mechanism of coupling between metabolic state and excitatory neurotransmission remains unknown. Previous work has shown that the vesicular glutamate transporters (VGLUTs) required for exocytotic release of glutamate undergo an unusual form of regulation by Cl(-). Using functional reconstitution of the purified VGLUTs into proteoliposomes, we now show that Cl(-) acts as an allosteric activator, and the ketone bodies that increase with fasting inhibit glutamate release by competing with Cl(-) at the site of allosteric regulation. Consistent with these observations, acetoacetate reduced quantal size at hippocampal synapses and suppresses glutamate release and seizures evoked with 4-aminopyridine in the brain. The results indicate an unsuspected link between metabolic state and excitatory neurotransmission through anion-dependent regulation of VGLUT activity. Copyright © 2010 Elsevier Inc. All rights reserved.

  1. Availability of neurotransmitter glutamate is diminished when beta-hydroxybutyrate replaces glucose in cultured neurons.

    Science.gov (United States)

    Lund, Trine M; Risa, Oystein; Sonnewald, Ursula; Schousboe, Arne; Waagepetersen, Helle S

    2009-07-01

    Ketone bodies serve as alternative energy substrates for the brain in cases of low glucose availability such as during starvation or in patients treated with a ketogenic diet. The ketone bodies are metabolized via a distinct pathway confined to the mitochondria. We have compared metabolism of [2,4-(13)C]beta-hydroxybutyrate to that of [1,6-(13)C]glucose in cultured glutamatergic neurons and investigated the effect of neuronal activity focusing on the aspartate-glutamate homeostasis, an essential component of the excitatory activity in the brain. The amount of (13)C incorporation and cellular content was lower for glutamate and higher for aspartate in the presence of [2,4-(13)C]beta-hydroxybutyrate as opposed to [1,6-(13)C]glucose. Our results suggest that the change in aspartate-glutamate homeostasis is due to a decreased availability of NADH for cytosolic malate dehydrogenase and thus reduced malate-aspartate shuttle activity in neurons using beta-hydroxybutyrate. In the presence of glucose, the glutamate content decreased significantly upon activation of neurotransmitter release, whereas in the presence of only beta-hydroxybutyrate, no decrease in the glutamate content was observed. Thus, the fraction of the glutamate pool available for transmitter release was diminished when metabolizing beta-hydroxybutyrate, which is in line with the hypothesis of formation of transmitter glutamate via an obligatory involvement of the malate-aspartate shuttle.

  2. Glutamate oxidation in astrocytes: Roles of glutamate dehydrogenase and aminotransferases

    DEFF Research Database (Denmark)

    McKenna, Mary C; Stridh, Malin H; McNair, Laura Frendrup

    2016-01-01

    to the presynaptic neurons as the nonexcitatory amino acid glutamine. The cycle was initially thought to function with a 1:1 ratio between glutamate released and glutamine taken up by neurons. However, studies of glutamate metabolism in astrocytes have shown that a considerable proportion of glutamate undergoes...... the enzymes that mediate this conversion. Methods include pharmacological tools such as the transaminase inhibitor aminooxyacetic acid, studies using GDH knockout mice, and siRNA-mediated knockdown of GDH in astrocytes. Studies in brain slices incubated with [15N]glutamate demonstrated activity of GDH......The cellular distribution of transporters and enzymes related to glutamate metabolism led to the concept of the glutamate–glutamine cycle. Glutamate is released as a neurotransmitter and taken up primarily by astrocytes ensheathing the synapses. The glutamate carbon skeleton is transferred back...

  3. Intracellular synthesis of glutamic acid in Bacillus methylotrophicus SK19.001, a glutamate-independent poly(γ-glutamic acid)-producing strain.

    Science.gov (United States)

    Peng, Yingyun; Zhang, Tao; Mu, Wanmeng; Miao, Ming; Jiang, Bo

    2016-01-15

    Bacillus methylotrophicus SK19.001 is a glutamate-independent strain that produces poly(γ-glutamic acid) (γ-PGA), a polymer of D- and L-glutamic acids that possesses applications in food, the environment, agriculture, etc. This study was undertaken to explore the synthetic pathway of intracellular L- and D-glutamic acid in SK19.001 by investigating the effects of tricarboxylic acid cycle intermediates and different amino acids as metabolic precursors on the production of γ-PGA and analyzing the activities of the enzymes involved in the synthesis of L- and D-glutamate. Tricarboxylic acid cycle intermediates and amino acids could participate in the synthesis of γ-PGA via independent pathways in SK19.001. L-Aspartate aminotransferase, L-glutaminase and L-glutamate synthase were the enzymatic sources of L-glutamate. Glutamate racemase was responsible for the formation of D-glutamate for the synthesis of γ-PGA, and the synthetase had stereoselectivity for glutamate substrate. The enzymatic sources of L-glutamate were investigated for the first time in the glutamate-independent γ-PGA-producing strain, and multiple enzymatic sources of L-glutamate were verified in SK19.001, which will benefit efforts to improve production of γ-PGA with metabolic engineering strategies. © 2015 Society of Chemical Industry.

  4. Radiation inactivation target size of rat adipocyte glucose transporters in the plasma membrane and intracellular pools

    International Nuclear Information System (INIS)

    Jacobs, D.B.; Berenski, C.J.; Spangler, R.A.; Jung, C.Y.

    1987-01-01

    The in situ assembly states of the glucose transport carrier protein in the plasma membrane and in the intracellular (microsomal) storage pool of rat adipocytes were assessed by studying radiation-induced inactivation of the D-glucose-sensitive cytochalasin B binding activities. High energy radiation inactivated the glucose-sensitive cytochalasin B binding of each of these membrane preparations by reducing the total number of the binding sites without affecting the dissociation constant. The reduction in total number of binding sites was analyzed as a function of radiation dose based on target theory, from which a radiation-sensitive mass (target size) was calculated. When the plasma membranes of insulin-treated adipocytes were used, a target size of approximately 58,000 daltons was obtained. For adipocyte microsomal membranes, we obtained target sizes of approximately 112,000 and 109,000 daltons prior to and after insulin treatment, respectively. In the case of microsomal membranes, however, inactivation data showed anomalously low radiation sensitivities at low radiation doses, which may be interpreted as indicating the presence of a radiation-sensitive inhibitor. These results suggest that the adipocyte glucose transporter occurs as a monomer in the plasma membrane while existing in the intracellular reserve pool either as a homodimer or as a stoichiometric complex with a protein of an approximately equal size

  5. Physical-chemical model for cellular uptake of fatty acids: prediction of intracellular pool sizes

    International Nuclear Information System (INIS)

    Cooper, R.; Noy, N.; Zakim, D.

    1987-01-01

    If the uptake of fatty acids by liver is a physical, not a biological, process, then the size and location of the intrahepatic pool of fatty acids can be predicted from uptake rates and thermodynamic data. The purpose of the experiments in this paper was to test the accuracy of this idea. Rat livers were perfused with [ 3 H] palmitate bound to [ 14 C] albumin, and the total amounts of palmitate removed from the perfusate were measured at 3-s intervals. The intrahepatic pools of palmitate calculated from these data were 13.8 and 23.0 nmol/g of liver at ratios of palmitate/albumin (mol/mol) (afferent side) of 2/1 and 4/1, respectively, in the steady state. The intrahepatic pools of palmitate calculated from the distributions of palmitate between membranes, H 2 O, albumin, and fatty acid binding protein and the measured first-order rate constants for acyl-CoA ligases in mitochondria and microsomes were 12.1 and 34.6 nmol/g for perfusate ratios of palmitate/albumin of 2/1 and 4/1, in the steady state. Intrahepatic pools of palmitate measured after establishment of a steady-state rate of uptake were 15.0 and 31.8 nmol/g for these ratios of palmitate/albumin of 2/1 and 4/1

  6. Evidence for evoked release of adenosine and glutamate from cultured cerebellar granule cells

    International Nuclear Information System (INIS)

    Schousboe, A.; Frandsen, A.; Drejer, J.

    1989-01-01

    Evoked release of [ 3 H]-D-aspartate which labels the neurotransmitter glutamate pool in cultured cerebellar granule cells was compared with evoked release of adenosine from similar cultures. It was found that both adenosine and [3H]-D-aspartate could be released from the neurons in a calcium dependent manner after depolarization of the cells with either 10-100 microM glutamate or 50 mM KCl. Cultures of cerebellar granule cells treated with 50 microM kainate to eliminate GABAergic neurons behaved in the same way. This together with the observation that cultured astrocytes did not exhibit a calcium dependent, potassium stimulated adenosine release strongly suggest that cerebellar granule cells release adenosine in a neurotransmitter-like fashion together with glutamate which is the classical neurotransmitter of these neurons. Studies of the metabolism of adenosine showed that in the granule cells adenosine is rapidly metabolized to ATP, ADP, and AMP, but in spite of this, adenosine was found to be released preferential to ATP

  7. Determination of an unrelated donor pool size for human leukocyte antigen-matched platelets in Brazil

    Directory of Open Access Journals (Sweden)

    Carolina Bonet Bub

    2016-02-01

    Full Text Available ABSTRACT Background: Successful transfusion of platelet refractory patients is a challenge. Many potential donors are needed to sustain human leukocyte antigen matched-platelet transfusion programs because of the different types of antigens and the constant needs of these patients. For a highly mixed population such as the Brazilian population, the pool size required to provide adequate platelet support is unknown. Methods: A mathematical model was created to estimate the appropriate size of an unrelated donor pool to provide human leukocyte antigen-compatible platelet support for a Brazilian population. A group of 154 hematologic human leukocyte antigen-typed patients was used as the potential patient population and a database of 65,500 human leukocyte antigen-typed bone marrow registered donors was used as the donor population. Platelet compatibility was based on the grading system of Duquesnoy. Results: Using the mathematical model, a pool containing 31,940, 1710 and 321 donors would be necessary to match more than 80% of the patients with at least five completely compatible (no cross-reactive group, partial compatible (one cross-reactive group or less compatible (two cross-reactive group donors, respectively. Conclusion: The phenotypic diversity of the Brazilian population has probably made it more difficulty to find completely compatible donors. However, this heterogeneity seems to have facilitated finding donors when cross-reactive groups are accepted as proposed by the grading system of Duquesnoy. The results of this study may help to establish unrelated human leukocyte antigen-compatible platelet transfusions, a procedure not routinely performed in most Brazilian transfusion services.

  8. A computational study of astrocytic glutamate influence on post-synaptic neuronal excitability.

    Directory of Open Access Journals (Sweden)

    Bronac Flanagan

    2018-04-01

    Full Text Available The ability of astrocytes to rapidly clear synaptic glutamate and purposefully release the excitatory transmitter is critical in the functioning of synapses and neuronal circuits. Dysfunctions of these homeostatic functions have been implicated in the pathology of brain disorders such as mesial temporal lobe epilepsy. However, the reasons for these dysfunctions are not clear from experimental data and computational models have been developed to provide further understanding of the implications of glutamate clearance from the extracellular space, as a result of EAAT2 downregulation: although they only partially account for the glutamate clearance process. In this work, we develop an explicit model of the astrocytic glutamate transporters, providing a more complete description of the glutamate chemical potential across the astrocytic membrane and its contribution to glutamate transporter driving force based on thermodynamic principles and experimental data. Analysis of our model demonstrates that increased astrocytic glutamate content due to glutamine synthetase downregulation also results in increased postsynaptic quantal size due to gliotransmission. Moreover, the proposed model demonstrates that increased astrocytic glutamate could prolong the time course of glutamate in the synaptic cleft and enhances astrocyte-induced slow inward currents, causing a disruption to the clarity of synaptic signalling and the occurrence of intervals of higher frequency postsynaptic firing. Overall, our work distilled the necessity of a low astrocytic glutamate concentration for reliable synaptic transmission of information and the possible implications of enhanced glutamate levels as in epilepsy.

  9. Diets high in resistent starch and arabinoxylan modulate digestion processes and SCFA pool size in the large intestine and faecal microbial composition in pigs

    DEFF Research Database (Denmark)

    Nielsen, Tina Skau; Lærke, Helle Nygaard; Theil, Peter Kappel

    2014-01-01

    The effects of a high level of dietary fibre (DF) either as arabinoxylan (AX) or resistant starch (RS) on digestion processes, SCFA concentration and pool size in various intestinal segments and on the microbial composition in the faeces were studied in a model experiment with pigs. A total...... resulted in a 3- to 5-fold higher pool size of butyrate compared with WSD feeding, with the RSD being intermediate (P microbial composition towards butyrogenic...

  10. Blood Glutamate Scavenging: Insight into Neuroprotection

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    Alexander Zlotnik

    2012-08-01

    Full Text Available Brain insults are characterized by a multitude of complex processes, of which glutamate release plays a major role. Deleterious excess of glutamate in the brain’s extracellular fluids stimulates glutamate receptors, which in turn lead to cell swelling, apoptosis, and neuronal death. These exacerbate neurological outcome. Approaches aimed at antagonizing the astrocytic and glial glutamate receptors have failed to demonstrate clinical benefit. Alternatively, eliminating excess glutamate from brain interstitial fluids by making use of the naturally occurring brain-to-blood glutamate efflux has been shown to be effective in various animal studies. This is facilitated by gradient driven transport across brain capillary endothelial glutamate transporters. Blood glutamate scavengers enhance this naturally occurring mechanism by reducing the blood glutamate concentration, thus increasing the rate at which excess glutamate is cleared. Blood glutamate scavenging is achieved by several mechanisms including: catalyzation of the enzymatic process involved in glutamate metabolism, redistribution of glutamate into tissue, and acute stress response. Regardless of the mechanism involved, decreased blood glutamate concentration is associated with improved neurological outcome. This review focuses on the physiological, mechanistic and clinical roles of blood glutamate scavenging, particularly in the context of acute and chronic CNS injury. We discuss the details of brain-to-blood glutamate efflux, auto-regulation mechanisms of blood glutamate, natural and exogenous blood glutamate scavenging systems, and redistribution of glutamate. We then propose different applied methodologies to reduce blood and brain glutamate concentrations and discuss the neuroprotective role of blood glutamate scavenging.

  11. ASTROCYTIC CONTROL OF BIOSYNTHESIS AND TURNOVER OF THE NEUROTRANSMITTERS GLUTAMATE AND GABA

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    Arne eSchousboe

    2013-08-01

    Full Text Available Glutamate and GABA are the quantitatively major neurotransmitters in the brain mediating excitatory and inhibitory signaling, respectively. These amino acids are metabolically interrelated and at the same time they are tightly coupled to the intermediary metabolism including energy homeostasis. Astrocytes play a pivotal role in the maintenance of the neurotransmitter pools of glutamate and GABA since only these cells express pyruvate carboxylase (PC, the enzyme required for de novo synthesis of the two amino acids. Such de novo synthesis is obligatory to compensate for catabolism of glutamate and GABA related to oxidative metabolism when the amino acids are used as energy substrates. This, in turn, is influenced by the extent to which the cycling of the amino acids between neurons and astrocytes may occur. This cycling is brought about by the glutamate/GABA – glutamine cycle the operation of which involves the enzymes glutamine synthetase (GS and glutaminase (PAG together with the plasma membrane transporters for glutamate, GABA and glutamine. The distribution of these proteins between neurons and astrocytes determines the efficacy of the cycle and it is of particular importance that GS is exclusively expressed in astrocytes. It should be kept in mind that the operation of the cycle is associated with movement of ammonia nitrogen between the two cell types and different mechanisms which can mediate this have been proposed.This review is intended to delineate the above mentioned processes and to discuss quantitatively their relative importance in the homeostatic mechanisms responsible for the maintenance of optimal conditions for the respective neurotransmission processes to operate.

  12. Glucose replaces glutamate as energy substrate to fuel glutamate uptake in glutamate dehydrogenase-deficient astrocytes

    DEFF Research Database (Denmark)

    Pajęcka, Kamilla; Nissen, Jakob D; Stridh, Malin H

    2015-01-01

    -500 µM) in the presence or in the absence of glucose, the metabolism of these substrates was studied by using tritiated glutamate or 2-deoxyglucose as tracers. In addition, the cellular contents of glutamate and ATP were determined. The astrocytes were able to maintain physiological levels of ATP...... regardless of the expression level of GDH and the incubation condition, indicating a high degree of flexibility with regard to regulatory mechanisms involved in maintaining an adequate energy level in the cells. Glutamate uptake was found to be increased in these cells when exposed to increasing levels...

  13. Long-term culture of astrocytes attenuates the readily releasable pool of synaptic vesicles.

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    Hiroyuki Kawano

    Full Text Available The astrocyte is a major glial cell type of the brain, and plays key roles in the formation, maturation, stabilization and elimination of synapses. Thus, changes in astrocyte condition and age can influence information processing at synapses. However, whether and how aging astrocytes affect synaptic function and maturation have not yet been thoroughly investigated. Here, we show the effects of prolonged culture on the ability of astrocytes to induce synapse formation and to modify synaptic transmission, using cultured autaptic neurons. By 9 weeks in culture, astrocytes derived from the mouse cerebral cortex demonstrated increases in β-galactosidase activity and glial fibrillary acidic protein (GFAP expression, both of which are characteristic of aging and glial activation in vitro. Autaptic hippocampal neurons plated on these aging astrocytes showed a smaller amount of evoked release of the excitatory neurotransmitter glutamate, and a lower frequency of miniature release of glutamate, both of which were attributable to a reduction in the pool of readily releasable synaptic vesicles. Other features of synaptogenesis and synaptic transmission were retained, for example the ability to induce structural synapses, the presynaptic release probability, the fraction of functional presynaptic nerve terminals, and the ability to recruit functional AMPA and NMDA glutamate receptors to synapses. Thus the presence of aging astrocytes affects the efficiency of synaptic transmission. Given that the pool of readily releasable vesicles is also small at immature synapses, our results are consistent with astrocytic aging leading to retarded synapse maturation.

  14. Glutamate availability is important in intramuscular amino acid metabolism and TCA cycle intermediates but does not affect peak oxidative metabolism

    DEFF Research Database (Denmark)

    Mourtzakis, M.; Graham, T.E.; Gonzalez-Alonso, J.

    2008-01-01

    Muscle glutamate is central to reactions producing 2-oxoglutarate, a tricarboxylic acid (TCA) cycle intermediate that essentially expands the TCA cycle intermediate pool during exercise. Paradoxically, muscle glutamate drops approximately 40-80% with the onset of exercise and 2-oxoglutarate...... declines in early exercise. To investigate the physiological relationship between glutamate, oxidative metabolism, and TCA cycle intermediates (i.e., fumarate, malate, 2-oxoglutarate), healthy subjects trained (T) the quadriceps of one thigh on the single-legged knee extensor ergometer (1 h/day at 70......% maximum workload for 5 days/wk), while their contralateral quadriceps remained untrained (UT). After 5 wk of training, peak oxygen consumption (VO2peak) in the T thigh was greater than that in the UT thigh (Pglutamate infusion. Peak...

  15. A new technique for measuring protein turnover in the gut, liver and kidneys of lean and obese mice with [3H] glutamic acid

    International Nuclear Information System (INIS)

    Miller, B.G.; Grimble, R.F.; Taylor, T.G.

    1978-01-01

    Measurements have been made of the incorporation of an intraperitoneal injection of [ 3 H]glutamate into the protein of the gut, liver and kidney of lean and obese siblings of the genetically obese mouse. Recycling of the 3 H was minimized by using glutamate labelled at the C-2 position. Loss of label from the amino acid pool by transamination and deamination was rapid, with a half-life of 4 h. In tissue protein the amino acid showing the highest 3 H radioactivity was glutamate. The half-lives for protein synthesis and catabolism were calculated from the decay curves of both specific and total radioactivity of [ 3 H] glutamate in tissue protein. No significant differences were found between kidney, liver and gut in lean and obese mice. (author)

  16. The glutamate/GABA-glutamine cycle

    DEFF Research Database (Denmark)

    Bak, Lasse K; Schousboe, Arne; Waagepetersen, Helle S

    2006-01-01

    Neurons are metabolically handicapped in the sense that they are not able to perform de novo synthesis of neurotransmitter glutamate and gamma-aminobutyric acid (GABA) from glucose. A metabolite shuttle known as the glutamate/GABA-glutamine cycle describes the release of neurotransmitter glutamate...... or GABA from neurons and subsequent uptake into astrocytes. In return, astrocytes release glutamine to be taken up into neurons for use as neurotransmitter precursor. In this review, the basic properties of the glutamate/GABA-glutamine cycle will be discussed, including aspects of transport and metabolism...... of intercellular transfer of ammonia produced in neurons (when glutamine is deamidated to glutamate) and utilized in astrocytes (for amidation of glutamate) when the glutamate/GABA-glutamine cycle is operating. A main objective of this review is to endorse the view that the glutamate/GABA-glutamine cycle must...

  17. Amino acid synthesis in photosynthesizing spinach cells: effects of ammonia on pool sizes and rates of labeling from 14CO2

    International Nuclear Information System (INIS)

    Larsen, P.O.; Cornwell, K.L.; Gee, S.L.; Bassham, J.A.

    1981-01-01

    Isolated cells from leaves of Spinacia oleracea have been maintained in a state capable of high rates of photosynthetic CO 2 fixation for more than 60 hours. The incorporation of 14 CO 2 under saturating CO 2 conditions into carbohydrates, carboxylic acids, and amino acids, and the effect of ammonia on this incorporation have been studied. Total incorporation, specific radioactivity, and pool size have been determined as a function of time for most of the protein amino acids and for γ-aminobutyric acid. The measurements of specific radio-activities and of the approaches to 14 C saturation of some amino acids indicate the presence and relative sizes of metabolically active and passive pools of these amino acids. Added ammonia decreased carbon fixation into carbohydrates and increased fixation into carboxylic acids and amino acids. The results indicate that added ammonia stimulates the reactions mediated by pyruvate kinase and phosphenoenolpyruvate carboxylase, as seen with other plant systems. The data on the effects of added ammonia on total labeling, pool sizes, and specific radioactivities of several amino acids provides a number of indications about the intracellular sites of principal synthesis from carbon skeletons of these amino acids and the selective nature of effects of increased intracellular ammonia concentration on-such synthesis

  18. 50 Hz hippocampal stimulation in refractory epilepsy: Higher level of basal glutamate predicts greater release of glutamate.

    Science.gov (United States)

    Cavus, Idil; Widi, Gabriel A; Duckrow, Robert B; Zaveri, Hitten; Kennard, Jeremy T; Krystal, John; Spencer, Dennis D

    2016-02-01

    The effect of electrical stimulation on brain glutamate release in humans is unknown. Glutamate is elevated at baseline in the epileptogenic hippocampus of patients with refractory epilepsy, and increases during spontaneous seizures. We examined the effect of 50 Hz stimulation on glutamate release and its relationship to interictal levels in the hippocampus of patients with epilepsy. In addition, we measured basal and stimulated glutamate levels in a subset of these patients where stimulation elicited a seizure. Subjects (n = 10) were patients with medically refractory epilepsy who were undergoing intracranial electroencephalography (EEG) evaluation in an epilepsy monitoring unit. Electrical stimulation (50 Hz) was delivered through implanted hippocampal electrodes (n = 11), and microdialysate samples were collected every 2 min. Basal glutamate, changes in glutamate efflux with stimulation, and the relationships between peak stimulation-associated glutamate concentrations, basal zero-flow levels, and stimulated seizures were examined. Stimulation of epileptic hippocampi in patients with refractory epilepsy caused increases in glutamate efflux (p = 0.005, n = 10), and 4 of ten patients experienced brief stimulated seizures. Stimulation-induced increases in glutamate were not observed during the evoked seizures, but rather were related to the elevation in interictal basal glutamate (R(2) = 0.81, p = 0.001). The evoked-seizure group had lower basal glutamate levels than the no-seizure group (p = 0.04), with no stimulation-induced change in glutamate efflux (p = 0.47, n = 4). Conversely, increased glutamate was observed following stimulation in the no-seizure group (p = 0.005, n = 7). Subjects with an atrophic hippocampus had higher basal glutamate levels (p = 0.03, n = 7) and higher stimulation-induced glutamate efflux. Electrical stimulation of the epileptic hippocampus either increased extracellular glutamate efflux or induced seizures. The magnitude of stimulated

  19. Effect of Molten Pool Size on Microstructure and Tensile Properties of Wire Arc Additive Manufacturing of Ti-6Al-4V Alloy.

    Science.gov (United States)

    Wu, Qianru; Lu, Jiping; Liu, Changmeng; Fan, Hongli; Shi, Xuezhi; Fu, Jie; Ma, Shuyuan

    2017-07-04

    Wire arc additive manufacturing (WAAM) technique is a cost-competitive and efficient technology to produce large structure components in industry domains. Mechanical properties are mainly dominated by the microstructure of the components, which is deeply affected by the molten pool size. In this work, to investigate the effect of the molten pool size on microstructure and mechanical properties of the components, a series of Ti-6Al-4V alloy blocks with different width of molten pool (WMP) ranging from 7 mm to 22 mm were deposited by adjusting the wire feed speed (WFS) from 100 cm/min to 500 cm/min. It is interesting to find that the macrostructure changes from columnar grains to equiaxial grains, and then returns to large columnar grains with the increase of WMP, which is mainly caused by the different cooling rates and thermal gradients. Nonetheless, the tensile properties of the components have a tendency to decline with the increase of WMP.

  20. Effect of Molten Pool Size on Microstructure and Tensile Properties of Wire Arc Additive Manufacturing of Ti-6Al-4V Alloy

    Directory of Open Access Journals (Sweden)

    Qianru Wu

    2017-07-01

    Full Text Available Wire arc additive manufacturing (WAAM technique is a cost-competitive and efficient technology to produce large structure components in industry domains. Mechanical properties are mainly dominated by the microstructure of the components, which is deeply affected by the molten pool size. In this work, to investigate the effect of the molten pool size on microstructure and mechanical properties of the components, a series of Ti-6Al-4V alloy blocks with different width of molten pool (WMP ranging from 7 mm to 22 mm were deposited by adjusting the wire feed speed (WFS from 100 cm/min to 500 cm/min. It is interesting to find that the macrostructure changes from columnar grains to equiaxial grains, and then returns to large columnar grains with the increase of WMP, which is mainly caused by the different cooling rates and thermal gradients. Nonetheless, the tensile properties of the components have a tendency to decline with the increase of WMP.

  1. Amperometric L-glutamate biosensor based on bacterial cell-surface displayed glutamate dehydrogenase

    Energy Technology Data Exchange (ETDEWEB)

    Liang, Bo [Laboratory for Biosensing, Key Laboratory of Biofuels, and Shandong Provinicial Key Laboratory of Energy Genetics, Qingdao Institute of Bioenergy & Bioprocess Technology, Chinese Academy of Sciences, 189 Songling Road, Qingdao 266101 (China); University of Chinese Academy of Sciences, 19A Yuquan Road, Beijing 100049 (China); Zhang, Shu [Laboratory for Biosensing, Key Laboratory of Biofuels, and Shandong Provinicial Key Laboratory of Energy Genetics, Qingdao Institute of Bioenergy & Bioprocess Technology, Chinese Academy of Sciences, 189 Songling Road, Qingdao 266101 (China); Key Laboratory of Marine Chemistry Theory and Technology of Ministry of Education, Ocean University of China, 238 Songling Road, Qingdao 266100 (China); Lang, Qiaolin [Laboratory for Biosensing, Key Laboratory of Biofuels, and Shandong Provinicial Key Laboratory of Energy Genetics, Qingdao Institute of Bioenergy & Bioprocess Technology, Chinese Academy of Sciences, 189 Songling Road, Qingdao 266101 (China); Song, Jianxia; Han, Lihui [Key Laboratory of Marine Chemistry Theory and Technology of Ministry of Education, Ocean University of China, 238 Songling Road, Qingdao 266100 (China); Liu, Aihua, E-mail: liuah@qibebt.ac.cn [Laboratory for Biosensing, Key Laboratory of Biofuels, and Shandong Provinicial Key Laboratory of Energy Genetics, Qingdao Institute of Bioenergy & Bioprocess Technology, Chinese Academy of Sciences, 189 Songling Road, Qingdao 266101 (China); University of Chinese Academy of Sciences, 19A Yuquan Road, Beijing 100049 (China)

    2015-07-16

    Highlights: • E. coli surface-dispalyed Gldh exhibiting excellent enzyme activity and stability. • Sensitive amperometric biosensor for glutamate using Gldh-bacteria and MWNTs. • The glutamate biosensor exhibited high specificity and stability. - Abstract: A novel L-glutamate biosensor was fabricated using bacteria surface-displayed glutamate dehydrogenase (Gldh-bacteria). Here the cofactor NADP{sup +}-specific dependent Gldh was expressed on the surface of Escherichia coli using N-terminal region of ice nucleation protein (INP) as the anchoring motif. The cell fractionation assay and SDS-PAGE analysis indicated that the majority of INP-Gldh fusion proteins were located on the surface of cells. The biosensor was fabricated by successively casting polyethyleneimine (PEI)-dispersed multi-walled carbon nanotubes (MWNTs), Gldh-bacteria and Nafion onto the glassy carbon electrode (Nafion/Gldh-bacteria/PEI-MWNTs/GCE). The MWNTs could not only significantly lower the oxidation overpotential towards NAPDH, which was the product of NADP{sup +} involving in the oxidation of glutamate by Gldh, but also enhanced the current response. Under the optimized experimental conditions, the current–time curve of the Nafion/Gldh-bacteria/PEI-MWNTs/GCE was performed at +0.52 V (vs. SCE) by amperometry varying glutamate concentration. The current response was linear with glutamate concentration in two ranges (10 μM–1 mM and 2–10 mM). The low limit of detection was estimated to be 2 μM glutamate (S/N = 3). Moreover, the proposed biosensor is stable, specific, reproducible and simple, which can be applied to real samples detection.

  2. Both dietary supplementation with monosodium L-glutamate and fat modify circulating and tissue amino acid pools in growing pigs, but with little interactive effect.

    Directory of Open Access Journals (Sweden)

    Zemeng Feng

    Full Text Available The Chinese population has undergone rapid transition to a high-fat diet. Furthermore, monosodium L-glutamate (MSG is widely used as a daily food additive in China. Little information is available on the effects of oral MSG and dietary fat supplementation on the amino acid balance in tissues. The present study aimed to determine the effects of both dietary fat and MSG on amino acid metabolism in growing pigs, and to assess any possible interactions between these two nutrients.Four iso-nitrogenous and iso-caloric diets (basal diet, high fat diet, basal diet with 3% MSG and high fat diet with 3% MSG were provided to growing pigs. The dietary supplementation with fat and MSG used alone and in combination were found to modify circulating and tissue amino acid pools in growing pigs. Both dietary fat and MSG modified the expression of gene related to amino acid transport in jejunum.Both dietary fat and MSG clearly influenced amino acid content in tissues but in different ways. Both dietary fat and MSG enhance the absorption of amino acids in jejunum. However, there was little interaction between the effects of dietary fat and MSG.

  3. Analysis of sodium pool fire in SFEF for assessing the limiting pool fire

    International Nuclear Information System (INIS)

    Mangarjuna Rao, P.; Ramesh, S.S.; Nashine, B.K.; Kasinathan, N.; Chellapandi, P.

    2011-01-01

    Accidental sodium leaks and resultant sodium fires in Liquid Metal Fast Breeder Reactor (LMFBR) systems can create a threat to the safe operation of the plant. To avoid this defence-in depth approach is implemented from the design stage of reactor itself. Rapid detection of sodium leak and fast dumping of the sodium into the storage tank of a defective circuit, leak collection trays, adequate lining of load bearing structural concrete and extinguishment of the sodium fire are the important defensive measures in the design, construction and operation of a LMFBR for protection against sodium leaks and their resultant fires. Evaluation of sodium leak events and their consequences by conducting large scale engineering experiments is very essential for effective implementation of the above protection measures for sodium fire safety. For this purpose a Sodium Fire Experimental Facility (SFEF) is constructed at SED, IGCAR. SFEF is having an experimental hall of size 9 m x 6 m x 10 m with 540 m 3 volume and its design pressure is 50 kPa. It is a concrete structure and provided with SS 304 liner, which is fixed to the inside surfaces of walls, ceiling and floor. A leak tight door of size (1.8 m x 2.0 m) is provided to the experimental hall and the facility is provided with a sodium equipment hall and a control room. Experimental evaluation of sodium pool fire consequences is an important activity in the LMFBR sodium fire safety related studies. An experimental program has been planned for different types of sodium fire studies in SFEF. A prior to that numerical analysis have been carried out for enclosed sodium pool fires using SOFIRE-II sodium pool fire code for SFEF experimental hall configuration to evaluate the limiting pool fire. This paper brings out results of the analysis carried out for this purpose. Limiting pool fire of SFEF depends on the exposed surface area of the pool, amount of sodium in the pool, oxygen concentration and initial sodium temperature. Limiting

  4. Glutamate dehydrogenase (RocG) in Bacillus licheniformis WX-02: Enzymatic properties and specific functions in glutamic acid synthesis for poly-γ-glutamic acid production.

    Science.gov (United States)

    Tian, Guangming; Wang, Qin; Wei, Xuetuan; Ma, Xin; Chen, Shouwen

    2017-04-01

    Poly-γ-glutamic acid (γ-PGA), a natural biopolymer, is widely used in cosmetics, medicine, food, water treatment, and agriculture owing to its features of moisture sequestration, cation chelation, non-toxicity and biodegradability. Intracellular glutamic acid, the substrate of γ-PGA, is a limiting factor for high yield in γ-PGA production. Bacillus subtilis and Bacillus licheniformis are both important γ-PGA producing strains, and B. subtilis synthesizes glutamic acid in vivo using the unique GOGAT/GS pathway. However, little is known about the glutamate synthesis pathway in B. licheniformis. The aim of this work was to characterize the glutamate dehydrogenase (RocG) in glutamic acid synthesis from B. licheniformis with both in vivo and in vitro experiments. By re-directing the carbon flux distribution, the rocG gene deletion mutant WX-02ΔrocG produced intracellular glutamic acid with a concentration of 90ng/log(CFU), which was only 23.7% that of the wild-type WX-02 (380ng/log(CFU)). Furthermore, the γ-PGA yield of mutant WX-02ΔrocG was 5.37g/L, a decrease of 45.3% compared to the wild type (9.82g/L). In vitro enzymatic assays of RocG showed that RocG has higher affinity for 2-oxoglutarate than glutamate, and the glutamate synthesis rate was far above degradation. This is probably the first study to reveal the glutamic acid synthesis pathway and the specific functions of RocG in B. licheniformis. The results indicate that γ-PGA production can be enhanced through improving intracellular glutamic acid synthesis. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Glutamate receptor agonists

    DEFF Research Database (Denmark)

    Vogensen, Stine Byskov; Greenwood, Jeremy R; Bunch, Lennart

    2011-01-01

    The neurotransmitter (S)-glutamate [(S)-Glu] is responsible for most of the excitatory neurotransmission in the central nervous system. The effect of (S)-Glu is mediated by both ionotropic and metabotropic receptors. Glutamate receptor agonists are generally a-amino acids with one or more...... stereogenic centers due to strict requirements in the agonist binding pocket of the activated state of the receptor. By contrast, there are many examples of achiral competitive antagonists. The present review addresses how stereochemistry affects the activity of glutamate receptor ligands. The review focuses...... mainly on agonists and discusses stereochemical and conformational considerations as well as biostructural knowledge of the agonist binding pockets, which is useful in the design of glutamate receptor agonists. Examples are chosen to demonstrate how stereochemistry not only determines how the agonist...

  6. Comparison of Glutamate Turnover in Nerve Terminals and Brain Tissue During [1,6-13C2]Glucose Metabolism in Anesthetized Rats.

    Science.gov (United States)

    Patel, Anant B; Lai, James C K; Chowdhury, Golam I M; Rothman, Douglas L; Behar, Kevin L

    2017-01-01

    The 13 C turnover of neurotransmitter amino acids (glutamate, GABA and aspartate) were determined from extracts of forebrain nerve terminals and brain homogenate, and fronto-parietal cortex from anesthetized rats undergoing timed infusions of [1,6- 13 C 2 ]glucose or [2- 13 C]acetate. Nerve terminal 13 C fractional labeling of glutamate and aspartate was lower than those in whole cortical tissue at all times measured (up to 120 min), suggesting either the presence of a constant dilution flux from an unlabeled substrate or an unlabeled (effectively non-communicating on the measurement timescale) glutamate pool in the nerve terminals. Half times of 13 C labeling from [1,6- 13 C 2 ]glucose, as estimated by least squares exponential fitting to the time course data, were longer for nerve terminals (Glu C4 , 21.8 min; GABA C2 21.0 min) compared to cortical tissue (Glu C4 , 12.4 min; GABA C2 , 14.5 min), except for Asp C3 , which was similar (26.5 vs. 27.0 min). The slower turnover of glutamate in the nerve terminals (but not GABA) compared to the cortex may reflect selective effects of anesthesia on activity-dependent glucose use, which might be more pronounced in the terminals. The 13 C labeling ratio for glutamate-C4 from [2- 13 C]acetate over that of 13 C-glucose was twice as large in nerve terminals compared to cortex, suggesting that astroglial glutamine under the 13 C glucose infusion was the likely source of much of the nerve terminal dilution. The net replenishment of most of the nerve terminal amino acid pools occurs directly via trafficking of astroglial glutamine.

  7. Glutamate and Neurodegenerative Disease

    Science.gov (United States)

    Schaeffer, Eric; Duplantier, Allen

    As the main excitatory neurotransmitter in the mammalian central nervous system, glutamate is critically involved in most aspects of CNS function. Given this critical role, it is not surprising that glutamatergic dysfunction is associated with many CNS disorders. In this chapter, we review the literature that links aberrant glutamate neurotransmission with CNS pathology, with a focus on neurodegenerative diseases. The biology and pharmacology of the various glutamate receptor families are discussed, along with data which links these receptors with neurodegenerative conditions. In addition, we review progress that has been made in developing small molecule modulators of glutamate receptors and transporters, and describe how these compounds have helped us understand the complex pharmacology of glutamate in normal CNS function, as well as their potential for the treatment of neurodegenerative diseases.

  8. Uptake and metabolism of L-[3H]glutamate and L-[3H]glutamine in adult rat cerebellar slices

    International Nuclear Information System (INIS)

    de Barry, J.; Vincendon, G.; Gombos, G.

    1983-01-01

    Using very low concentrations (1 mumol range) of L-2-3-[ 3 H]glutamate, ( 3 H-Glu) or L-2-3-[ 3 H]glutamine ( 3 H-Gln), the authors have previously shown by autoradiography that these amino acids were preferentially taken up in the molecular layer of the cerebellar cortex. Furthermore, the accumulation of 3 H-Glu was essentially glial in these conditions. Uptake and metabolism of either ( 3 H-Glu) or ( 3 H-Gln) were studied in adult rat cerebellar slices. Both amino acids were rapidly converted into other metabolic compounds: after seven minutes of incubation in the presence of exogenous 3 H-Glu, 70% of the tissue accumulated radioactivity was found to be in compounds other than glutamate. The main metabolites were Gln (42%), alpha-ketoglutarate (25%) and GABA (1,4%). In the presence of exogenous 3 H-Gln the rate of metabolism was slightly slower (50% after seven minutes of incubation) and the metabolites were also Glu (29%), alpha-ketoglutarate (15%) and GABA (5%). Using depolarizing conditions (56 mM KCl) with either exogenous 3 H-Glu or 3 H-Gln, the radioactivity was preferentially accumulated in glutamate compared to control. From these results we conclude: i) there are two cellular compartments for the neurotransmission-glutamate-glutamine cycle; one is glial, the other neuronal; ii) these two cellular compartments contain both Gln and Glu; iii) transmitter glutamate is always in equilibrium with the so-called ''metabolic'' pool of glutamate; iv) the regulation of the glutamate-glutamine cycle occurs at least at two different levels: the uptake of glutamate and the enzymatic activity of the neuronal glutaminase

  9. A Genome Wide Association Study Links Glutamate Receptor Pathway to Sporadic Creutzfeldt-Jakob Disease Risk

    Science.gov (United States)

    Sanchez-Juan, Pascual; Bishop, Matthew T.; Kovacs, Gabor G.; Calero, Miguel; Aulchenko, Yurii S.; Ladogana, Anna; Boyd, Alison; Lewis, Victoria; Ponto, Claudia; Calero, Olga; Poleggi, Anna; Carracedo, Ángel; van der Lee, Sven J.; Ströbel, Thomas; Rivadeneira, Fernando; Hofman, Albert; Haïk, Stéphane; Combarros, Onofre; Berciano, José; Uitterlinden, Andre G.; Collins, Steven J.; Budka, Herbert; Brandel, Jean-Philippe; Laplanche, Jean Louis; Pocchiari, Maurizio; Zerr, Inga; Knight, Richard S. G.; Will, Robert G.; van Duijn, Cornelia M.

    2015-01-01

    We performed a genome-wide association (GWA) study in 434 sporadic Creutzfeldt-Jakob disease (sCJD) patients and 1939 controls from the United Kingdom, Germany and The Netherlands. The findings were replicated in an independent sample of 1109 sCJD and 2264 controls provided by a multinational consortium. From the initial GWA analysis we selected 23 SNPs for further genotyping in 1109 sCJD cases from seven different countries. Five SNPs were significantly associated with sCJD after correction for multiple testing. Subsequently these five SNPs were genotyped in 2264 controls. The pooled analysis, including 1543 sCJD cases and 4203 controls, yielded two genome wide significant results: rs6107516 (p-value=7.62x10-9) a variant tagging the prion protein gene (PRNP); and rs6951643 (p-value=1.66x10-8) tagging the Glutamate Receptor Metabotropic 8 gene (GRM8). Next we analysed the data stratifying by country of origin combining samples from the pooled analysis with genotypes from the 1000 Genomes Project and imputed genotypes from the Rotterdam Study (Total n=12967). The meta-analysis of the results showed that rs6107516 (p-value=3.00x10-8) and rs6951643 (p-value=3.91x10-5) remained as the two most significantly associated SNPs. Rs6951643 is located in an intronic region of GRM8, a gene that was additionally tagged by a cluster of 12 SNPs within our top100 ranked results. GRM8 encodes for mGluR8, a protein which belongs to the metabotropic glutamate receptor family, recently shown to be involved in the transduction of cellular signals triggered by the prion protein. Pathway enrichment analyses performed with both Ingenuity Pathway Analysis and ALIGATOR postulates glutamate receptor signalling as one of the main pathways associated with sCJD. In summary, we have detected GRM8 as a novel, non-PRNP, genome-wide significant marker associated with heightened disease risk, providing additional evidence supporting a role of glutamate receptors in sCJD pathogenesis. PMID:25918841

  10. Inhibitors of glutamate dehydrogenase block sodium-dependent glutamate uptake in rat brain membranes

    Directory of Open Access Journals (Sweden)

    Brendan S Whitelaw

    2013-09-01

    Full Text Available We recently found evidence for anatomic and physical linkages between the astroglial Na+-dependent glutamate transporters (GLT-1/EAAT2 and GLAST/EAAT1 and mitochondria. In these same studies, we found that the glutamate dehydrogenase (GDH inhibitor, epigallocatechin-monogallate (EGCG, inhibits both glutamate oxidation and Na+-dependent glutamate uptake in astrocytes. In the present study, we extend this finding by exploring the effects of EGCG on Na+-dependent L-[3H]-glutamate (Glu uptake in crude membranes (P2 prepared from rat brain cortex. In this preparation, uptake is almost exclusively mediated by GLT-1. EGCG inhibited L-[3H]-Glu uptake in cortical membranes with an IC50 value of 230 µM. We also studied the effects of two additional inhibitors of GDH, hexachlorophene (HCP and bithionol (BTH. Both of these compounds also caused concentration-dependent inhibition of glutamate uptake in cortical membranes. Pre-incubating with HCP for up to 15 min had no greater effect than that observed with no pre-incubation, showing that the effects occur rapidly. HCP decreased the Vmax for glutamate uptake without changing the Km, consistent with a non-competitive mechanism of action. EGCG, HCP, and BTH also inhibited Na+-dependent transport of D-[3H]-aspartate (Asp, a non-metabolizable substrate, and [3H]-γ-aminobutyric acid (GABA. In contrast to the forebrain, glutamate uptake in crude cerebellar membranes (P2 is likely mediated by GLAST (EAAT1. Therefore, the effects of these compounds were examined in cerebellar membranes. In this region, none of these compounds had any effect on uptake of either L-[3H]-Glu or D-[3H]-Asp, but they all inhibited [3H]-GABA uptake. Together these studies suggest that GDH is preferentially required for glutamate uptake in forebrain as compared to cerebellum, and GDH may be required for GABA uptake as well. They also provide further evidence for a functional linkage between glutamate transport and mitochondria.

  11. Cardioprotective effect of L-glutamate in obese type 2 diabetic Zucker fatty rats

    DEFF Research Database (Denmark)

    Povlsen, Jonas Agerlund; Løfgren, Bo; Rasmussen, Lars Ege

    2009-01-01

    (Wistar-Kyoto) and diabetic (Zucker diabetic fatty (ZDF)) rats, studied at 16 weeks of age. The infarct size (IS)/area-at-risk (AAR) ratio was the primary end-point. Expression of L-glutamate excitatory amino acid transporter (EAAT) 1 (mitochondrial) and EAAT3 (sarcolemmal) was determined by quantitative...... was downregulated in hearts from ZDF rats at both the mRNA and protein levels (P diabetic hearts (P obese diabetic rats have......1. Because diabetic hearts have an increased threshold for cardioprotection by ischaemic preconditioning (IPC), we hypothesized that protection by L-glutamate during reperfusion is restricted in Type 2 diabetic hearts. Previously, we found that L-glutamate-mediated postischaemic cardioprotection...

  12. Cardioprotective effect of L-glutamate in obese type 2 diabetic Zucker fatty rats

    DEFF Research Database (Denmark)

    Povlsen, Jonas Agerlund; Løfgren, Bo; Rasmussen, Lars Ege

    2009-01-01

    (Wistar-Kyoto) and diabetic (Zucker diabetic fatty (ZDF)) rats, studied at 16 weeks of age. The infarct size (IS)/area-at-risk (AAR) ratio was the primary end-point. Expression of L-glutamate excitatory amino acid transporter (EAAT) 1 (mitochondrial) and EAAT3 (sarcolemmal) was determined by quantitative......1. Because diabetic hearts have an increased threshold for cardioprotection by ischaemic preconditioning (IPC), we hypothesized that protection by L-glutamate during reperfusion is restricted in Type 2 diabetic hearts. Previously, we found that L-glutamate-mediated postischaemic cardioprotection...... mimics IPC. 2. Rat hearts were studied in a Langendorff preparation perfused with Krebs'-Henseleit solution and subjected to 40 min global no-flow ischaemia, followed by 120 min reperfusion. L-Glutamate (0, 15 and 30 mmol/L) was added to the perfusate during reperfusion of hearts from non-diabetic...

  13. Glutamic acid as anticancer agent: An overview.

    Science.gov (United States)

    Dutta, Satyajit; Ray, Supratim; Nagarajan, K

    2013-10-01

    The objective of the article is to highlight various roles of glutamic acid like endogenic anticancer agent, conjugates to anticancer agents, and derivatives of glutamic acid as possible anticancer agents. Besides these emphases are given especially for two endogenous derivatives of glutamic acid such as glutamine and glutamate. Glutamine is a derivative of glutamic acid and is formed in the body from glutamic acid and ammonia in an energy requiring reaction catalyzed by glutamine synthase. It also possesses anticancer activity. So the transportation and metabolism of glutamine are also discussed for better understanding the role of glutamic acid. Glutamates are the carboxylate anions and salts of glutamic acid. Here the roles of various enzymes required for the metabolism of glutamates are also discussed.

  14. Prefrontal changes in the glutamate-glutamine cycle and neuronal/glial glutamate transporters in depression with and without suicide

    NARCIS (Netherlands)

    Zhao, J.; Verwer, R.W.H.; van Wamelen, D.J.; Qi, X.R.; Gao, S.F.; Lucassen, P.J.; Swaab, D.F.

    2016-01-01

    There are indications for changes in glutamate metabolism in relation to depression or suicide. The glutamate-glutamine cycle and neuronal/glial glutamate transporters mediate the uptake of the glutamate and glutamine. The expression of various components of the glutamate-glutamine cycle and the

  15. Glutamate availability is important in intramuscular amino acid metabolism and TCA cycle intermediates but does not affect peak oxidative metabolism.

    Science.gov (United States)

    Mourtzakis, M; Graham, T E; González-Alonso, J; Saltin, B

    2008-08-01

    Muscle glutamate is central to reactions producing 2-oxoglutarate, a tricarboxylic acid (TCA) cycle intermediate that essentially expands the TCA cycle intermediate pool during exercise. Paradoxically, muscle glutamate drops approximately 40-80% with the onset of exercise and 2-oxoglutarate declines in early exercise. To investigate the physiological relationship between glutamate, oxidative metabolism, and TCA cycle intermediates (i.e., fumarate, malate, 2-oxoglutarate), healthy subjects trained (T) the quadriceps of one thigh on the single-legged knee extensor ergometer (1 h/day at 70% maximum workload for 5 days/wk), while their contralateral quadriceps remained untrained (UT). After 5 wk of training, peak oxygen consumption (VO2peak) in the T thigh was greater than that in the UT thigh (PTCA cycle intermediates. In the UT thigh, peak exercise (vs. rest) induced an increase in fumarate (0.33+/-0.07 vs. 0.02+/-0.01 mmol/kg dry wt (dw), PTCA cycle, glutamate and TCA cycle intermediates do not directly affect VO2peak in either trained or untrained muscle.

  16. Microbial communities in litter and soil - particles size fractionation, C- and N-pools and soil enzymes

    International Nuclear Information System (INIS)

    Stemmer, M.; Gerzabek, M.H.; Pichlmayer, F.; Kandeler, E.

    1995-08-01

    In this study we try to correlate C and N pool investigations to enzyme activities in particle size fractions of soils. Soil incubations in the lab (for one year) simulate two different conventional tillage treatments : (i) soil mixed with maize straw (GSF-mixed) and (ii) soil with maize straw lying on the top (home-mixed). The control soil is incubated without any amendment. The separation of the particle size fractions (2000 - 200 μm, 200 - 63 μm, 63 - 2 μm, 2 - 0.1 μm and 0.1 - 0 μm) is realized by a combination of wet-sieving and centrifugation. To disrupt aggregates we use a defined low-energy ultrasonication, which partly preserves microaggregates. The decomposition of organic C during the incubation can be observed clearly, the small amount of N in the added maize straw complicates the analysis. The isotopic measurements of δ13C and δ15N provide valuable additional informations in this context. Both enzymes, saccharase and xylanase, seem to react in a more sensitive way on the incorporation of the maize litter, than the chemical analysis of the pools. The saccharase activity, which seems to be a sensitive indicator for microbial biomass, shows different behaviour between the mix- and top-treatment. The xylanase activity is mainly located in the coarse sand fraction, this extracellular enzyme might be adsorbed by the particulate organic matter. The transfer of adhering coatings and small particles of the added maize to small sized particles during the fractionation procedure and the 'passive role' of the silt fraction, which could be due to the used method, are nonexpected results. (author)

  17. Amperometric L-glutamate biosensor based on bacterial cell-surface displayed glutamate dehydrogenase.

    Science.gov (United States)

    Liang, Bo; Zhang, Shu; Lang, Qiaolin; Song, Jianxia; Han, Lihui; Liu, Aihua

    2015-07-16

    A novel L-glutamate biosensor was fabricated using bacteria surface-displayed glutamate dehydrogenase (Gldh-bacteria). Here the cofactor NADP(+)-specific dependent Gldh was expressed on the surface of Escherichia coli using N-terminal region of ice nucleation protein (INP) as the anchoring motif. The cell fractionation assay and SDS-PAGE analysis indicated that the majority of INP-Gldh fusion proteins were located on the surface of cells. The biosensor was fabricated by successively casting polyethyleneimine (PEI)-dispersed multi-walled carbon nanotubes (MWNTs), Gldh-bacteria and Nafion onto the glassy carbon electrode (Nafion/Gldh-bacteria/PEI-MWNTs/GCE). The MWNTs could not only significantly lower the oxidation overpotential towards NAPDH, which was the product of NADP(+) involving in the oxidation of glutamate by Gldh, but also enhanced the current response. Under the optimized experimental conditions, the current-time curve of the Nafion/Gldh-bacteria/PEI-MWNTs/GCE was performed at +0.52 V (vs. SCE) by amperometry varying glutamate concentration. The current response was linear with glutamate concentration in two ranges (10 μM-1 mM and 2-10 mM). The low limit of detection was estimated to be 2 μM glutamate (S/N=3). Moreover, the proposed biosensor is stable, specific, reproducible and simple, which can be applied to real samples detection. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Swimming Pool Safety

    Science.gov (United States)

    ... Spread the Word Shop AAP Find a Pediatrician Safety & Prevention Immunizations All Around At Home At Play ... Español Text Size Email Print Share Swimming Pool Safety Page Content ​What is the best way to ...

  19. Circadian Regulation of Glutamate Transporters

    Directory of Open Access Journals (Sweden)

    Donají Chi-Castañeda

    2018-06-01

    Full Text Available L-glutamate is the major excitatory amino acid in the mammalian central nervous system (CNS. This neurotransmitter is essential for higher brain functions such as learning, cognition and memory. A tight regulation of extra-synaptic glutamate levels is needed to prevent a neurotoxic insult. Glutamate removal from the synaptic cleft is carried out by a family of sodium-dependent high-affinity transporters, collectively known as excitatory amino acid transporters. Dysfunction of glutamate transporters is generally involved in acute neuronal injury and neurodegenerative diseases, so characterizing and understanding the mechanisms that lead to the development of these disorders is an important goal in the design of novel treatments for the neurodegenerative diseases. Increasing evidence indicates glutamate transporters are controlled by the circadian system in direct and indirect manners, so in this contribution we focus on the mechanisms of circadian regulation (transcriptional, translational, post-translational and post-transcriptional regulation of glutamate transport in neuronal and glial cells, and their consequence in brain function.

  20. Environmental controls of C, N and P biogeochemistry in peatland pools.

    Science.gov (United States)

    Arsenault, Julien; Talbot, Julie; Moore, Tim R

    2018-08-01

    Pools are common in northern peatlands but studies have seldom focused on their nutrient biogeochemistry, especially in relation to their morphological characteristics and through seasons. We determined the environmental characteristics controlling carbon (C), nitrogen (N) and phosphorus (P) biogeochemistry in pools and assessed their evolution over the course of the 2016 growing season in a subboreal ombrotrophic peatland of eastern Canada. We showed that water chemistry variations in 62 pools were significantly explained by depth (81.9%) and the surrounding vegetation type (14.8%), but not by pool area or shape. Shallow pools had larger dissolved organic carbon (DOC) and total nitrogen (TN) concentrations and lower pH than deep pools, while pools surrounded by coniferous trees had more recalcitrant DOC than pools where vegetation was dominated by mosses. The influence of depth on pool biogeochemistry was confirmed by the seasonal survey of pools of different sizes with 47.1% of the variation in pool water chemistry over time significantly explained. Of this, 67.3% was explained by the interaction between time and pool size and 32.7% by pool size alone. P concentrations were small in all pools all summer long and combined with high N:P ratios, are indicative of P-limitation. Our results show that pool biogeochemistry is influenced by internal processes and highlight the spatial and temporal heterogeneity of nutrient biogeochemistry in ombrotrophic peatlands. Copyright © 2018 Elsevier B.V. All rights reserved.

  1. Glutamic acid as anticancer agent: An overview

    OpenAIRE

    Dutta, Satyajit; Ray, Supratim; Nagarajan, K.

    2013-01-01

    The objective of the article is to highlight various roles of glutamic acid like endogenic anticancer agent, conjugates to anticancer agents, and derivatives of glutamic acid as possible anticancer agents. Besides these emphases are given especially for two endogenous derivatives of glutamic acid such as glutamine and glutamate. Glutamine is a derivative of glutamic acid and is formed in the body from glutamic acid and ammonia in an energy requiring reaction catalyzed by glutamine synthase. I...

  2. Protein Restriction with Amino Acid-Balanced Diets Shrinks Circulating Pool Size of Amino Acid by Decreasing Expression of Specific Transporters in the Small Intestine.

    Directory of Open Access Journals (Sweden)

    Kai Qiu

    Full Text Available Dietary protein restriction is not only beneficial to health and longevity in humans, but also protects against air pollution and minimizes feeding cost in livestock production. However, its impact on amino acid (AA absorption and metabolism is not quite understood. Therefore, the study aimed to explore the effect of protein restriction on nitrogen balance, circulating AA pool size, and AA absorption using a pig model. In Exp.1, 72 gilts weighting 29.9 ± 1.5 kg were allocated to 1 of the 3 diets containing 14, 16, or 18% CP for a 28-d trial. Growth (n = 24, nitrogen balance (n = 6, and the expression of small intestinal AA and peptide transporters (n = 6 were evaluated. In Exp.2, 12 barrows weighting 22.7 ± 1.3 kg were surgically fitted with catheters in the portal and jejunal veins as well as the carotid artery and assigned to a diet containing 14 or 18% CP. A series of blood samples were collected before and after feeding for determining the pool size of circulating AA and AA absorption in the portal vein, respectively. Protein restriction did not sacrifice body weight gain and protein retention, since nitrogen digestibility was increased as dietary protein content reduced. However, the pool size of circulating AA except for lysine and threonine, and most AA flux through the portal vein were reduced in pigs fed the low protein diet. Meanwhile, the expression of peptide transporter 1 (PepT-1 was stimulated, but the expression of the neutral and cationic AA transporter systems was depressed. These results evidenced that protein restriction with essential AA-balanced diets, decreased AA absorption and reduced circulating AA pool size. Increased expression of small intestinal peptide transporter PepT-1 could not compensate for the depressed expression of jejunal AA transporters for AA absorption.

  3. Release of [3H]GABA formed from [3H]glutamate in rat hippocampal slices: comparison with endogenous and exogenous labeled GABA

    International Nuclear Information System (INIS)

    Szerb, J.C.

    1983-01-01

    To compare the storage and release of endogenous GABA, of [ 3 H]GABA formed endogenously from glutamate, and of exogenous [ 14 C]GABA, hippocampal slices were incubated with 5 microCi/ml [3,4- 3 H]1-glutamate and 0.5 microCi/ml [U- 14 C]GABA and then were superfused in the presence or absence of Ca + with either 50 mM K + or 50 microM veratridine. Exogenous [ 14 C]GABA content of the slices declined spontaneously while endogenous GABA and endogenously formed [ 3 H]GABA stayed constant over a 48 min period. In the presence of Ca + 50 mM K + and in the presence or absence of Ca2 + veratridine released exogenous [ 14 C]GABA more rapidly than endogenous or endogenously formed [ 3 H]GABA, the release of the latter two occurring always in parallel. The initial specific activity of released exogenous [ 14 C]GABA was three times, while that of endogenously formed [ 3 H]GABA was only 50% higher than that in the slices. The observation that endogenous GABA and [ 3 H]GABA formed endogenously from glutamate are stored and released in parallel but differently from exogenous labelled GABA, suggests that exogenous [ 3 H] glutamate can enter a glutamate pool that normally serves as precursor of GABA

  4. Benthic assemblages of rock pools in northern Portugal: seasonal and between-pool variability

    Directory of Open Access Journals (Sweden)

    Iacopo Bertocci

    2012-11-01

    Full Text Available We investigated the seasonal (winter vs summer and within season and spatial (between-pool variability of benthic assemblages of rock pools at mid-intertidal level along the shore of Viana do Castelo (North Portugal. Physical traits of rock pools, including size, depth and position along the shore, were also compared between pools. While pools did not differ for any of the examined physical traits, results indicated a clear seasonal difference in the structure of assemblages, including a total of 49 macroalgal and 13 animal taxa. This finding was driven by six taxa that are more abundant in winter (the reef-forming polychaete Sabellaria alveolata, the articulated coralline algae Corallina spp., the brown alga Bifurcaria bifurcata, the encrusting coralline alga Lithophyllum incrustans, the red alga Chondracanthus acicularis and the grazing snails Gibbula spp. and four algal taxa that are more abundant in summer (the invasive brown Sargassum muticum, the green Ulva spp., the kelp Laminaria ochroleuca and the filamentous red Ceramium spp.. These data provide a new contribution to the knowledge of rock pool systems and have potential implications for monitoring programmes aimed at assessing ecological modifications related to natural and anthropogenic disturbances and for identifying processes responsible for the variability of rock pool assemblages.

  5. Glutamate monitoring in vitro and in vivo: recent progress in the field of glutamate biosensors

    DEFF Research Database (Denmark)

    Rieben, Nathalie Ines; Rose, Nadia Cherouati; Martinez, Karen Laurence

    2009-01-01

    is currently the most common method for in vivo glutamate sampling. However, the recent development and improvement of enzyme-based amperometric glutamate biosensors makes them a promising alternative to microdialysis for in vivo applications, as well as valuable devices for in vitro applications in basic......, and different techniques have been developed to this end. This review presents and discusses these techniques, especially the recent progress in the field of glutamate biosensors, as well as the great potential of nanotechnology in glutamate sensing. Microdialysis coupled to analytical detection techniques...... neurobiological research. Another interesting group of biosensors for glutamate are fluorescence-based glutamate biosensors, which have unsurpassed spatio-temporal resolution and are therefore important tools for investigating glutamate dynamics during signaling. Adding to this list are biosensors based on nano...

  6. Glutamate Efflux at the Blood-Brain Barrier

    DEFF Research Database (Denmark)

    Cederberg-Helms, Hans Christian; Uhd-Nielsen, Carsten; Brodin, Birger

    2014-01-01

    is well known, however endothelial cells may also play an important role through mediating brain-to-blood L-glutamate efflux. Expression of excitatory amino acid transporters has been demonstrated in brain endothelial cells of bovine, human, murine, rat and porcine origin. These can account for high...... affinity concentrative uptake of L-glutamate from the brain interstitial fluid into the capillary endothelial cells. The mechanisms in between L-glutamate uptake in the endothelial cells and L-glutamate appearing in the blood are still unclear and may involve a luminal transporter for L......-glutamate, metabolism of L-glutamate and transport of metabolites or a combination of the two. However, both in vitro and in vivo studies have demonstrated blood-to-brain transport of L-glutamate, at least during pathological events. This review summarizes the current knowledge on the brain-to-blood L-glutamate efflux...

  7. The Degradation of 14C-Glutamic Acid by L-Glutamic Acid Decarboxylase.

    Science.gov (United States)

    Dougherty, Charles M; Dayan, Jean

    1982-01-01

    Describes procedures and semi-micro reaction apparatus (carbon dioxide trap) to demonstrate how a particular enzyme (L-Glutamic acid decarboxylase) may be used to determine the site or sites of labeling in its substrate (carbon-14 labeled glutamic acid). Includes calculations, solutions, and reagents used. (Author/SK)

  8. Opportunities and challenges when pooling milk samples using ELISA

    DEFF Research Database (Denmark)

    Græsbøll, Kaare; Andresen, Lars Ole; Hisham Beshara Halasa, Tariq

    2017-01-01

    -positive samples by pooling. To illustrate this, the sensitivity of antibody ELISA on pooled samples of bovine milk for Salmonella Dublin, Mycobacterium avium spp. paratuberculosis, and bovine virus diarrhea was tested. For these milk assays, the analytical sensitivity decreased rapidly with increasing pool sizes...

  9. Radiometric microassay for glutamic acid decarboxylase

    Energy Technology Data Exchange (ETDEWEB)

    Maderdrut, J L [North Carolina Dept. of Mental Health, Raleigh (USA); North Carolina Univ., Chapel Hill (USA). School of Medicine)

    1979-01-01

    A simple method for purifying L-(/sup 3/H) glutamic acid and incubation conditions suitable for estimating L-glutamic acid decarboxylase activity are described. Routine and recycled cation-exchange procedure for separating ..gamma..-aminobutyric acid from L-glutamate are outlined and compared. Recycling increases the sensitivity of the cation-exchange method by 6-7 fold. L-Glutamate decarboxylase activity can be measured reliably in samples of embryonic neural tissue having wet-weights of approximately 1 ..mu..g. The cation-exchange method is compared with the anion-exchange and CO/sub 2/-trapping methods. L-Glutamate decarboxylase activity has been detected in the lumbar spinal cord of the chick embryo at Day 21/4 (stage 14) using the cation-exchange method. This is 5-6 days earlier than L-glutamate decarboxylase activity has been detected in embryonic neural tissue by previous investigators. L-Glutamate decarboxylase is present in the lumbar spinal cord at least as early as the birth of the first lumbar spinal cord neurons and at least 1-2 days before the initiation of synaptogenesis.

  10. Amino acid transamination is crucial for ischaemic cardioprotection in normal and preconditioned isolated rat hearts--focus on L-glutamate

    DEFF Research Database (Denmark)

    Løfgren, Bo; Povlsen, Jonas Agerlund; Rasmussen, Lars Ege

    2010-01-01

    We have found that cardioprotection by l-glutamate mimics protection by classical ischaemic preconditioning (IPC). We investigated whether the effect of IPC involves amino acid transamination and whether IPC modulates myocardial glutamate metabolism. In a glucose-perfused, isolated rat heart model...... subjected to 40 min global no-flow ischaemia and 120 min reperfusion, the effects of IPC (2 cycles of 5 min ischaemia and 5 min reperfusion) and continuous glutamate (20 mm) administration during reperfusion on infarct size and haemodynamic recovery were studied. The effect of inhibiting amino acid...... transamination was evaluated by adding the amino acid transaminase inhibitor amino-oxyacetate (AOA; 0.025 mm) during reperfusion. Changes in coronary effluent, interstitial (microdialysis) and intracellular glutamate ([GLUT](i)) concentrations were measured. Ischaemic preconditioning and postischaemic glutamate...

  11. Glutamate: Tastant and Neuromodulator in Taste Buds.

    Science.gov (United States)

    Vandenbeuch, Aurelie; Kinnamon, Sue C

    2016-07-01

    In taste buds, glutamate plays a double role as a gustatory stimulus and neuromodulator. The detection of glutamate as a tastant involves several G protein-coupled receptors, including the heterodimer taste receptor type 1, member 1 and 3 as well as metabotropic glutamate receptors (mGluR1 and mGluR4). Both receptor types participate in the detection of glutamate as shown with knockout animals and selective antagonists. At the basal part of taste buds, ionotropic glutamate receptors [N-methyl-d-aspartate (NMDA) and non-NMDA] are expressed and participate in the modulation of the taste signal before its transmission to the brain. Evidence suggests that glutamate has an efferent function on taste cells and modulates the release of other neurotransmitters such as serotonin and ATP. This short article reviews the recent developments in the field with regard to glutamate receptors involved in both functions as well as the influence of glutamate on the taste signal. © 2016 American Society for Nutrition.

  12. Pool Boiling CHF in Inclined Narrow Annuli

    International Nuclear Information System (INIS)

    Kang, Myeong Gie

    2010-01-01

    Pool boiling heat transfer has been studied extensively since it is frequently encountered in various heat transfer equipment. Recently, it has been widely investigated in nuclear power plants for application to the advanced light water reactors designs. Through the review on the published results it can be concluded that knowledge on the combined effects of the surface orientation and a confined space on pool boiling heat transfer is of great practical importance and also of great academic interest. Fujita et al. investigated pool boiling heat transfer, from boiling inception to the critical heat flux (CHF, q' CHF ), in a confined narrow space between heated and unheated parallel rectangular plates. They identified that both the confined space and the surface orientation changed heat transfer much. Kim and Suh changed the surface orientation angles of a downward heating rectangular channel having a narrow gap from the downward-facing position (180 .deg.) to the vertical position (90 .deg.). They observed that the CHF generally decreased as the inclination angle (θ ) increased. Yao and Chang studied pool boiling heat transfer in a confined heat transfer for vertical narrow annuli with closed bottoms. They observed that when the gap size ( s ) of the annulus was decreased the effect of space confinement to boiling heat transfer increased. The CHF was occurred at much lower value for the confined space comparing to the unconfined pool boiling. Pool boiling heat transfer in narrow horizontal annular crevices was studied by Hung and Yao. They concluded that the CHF decreased with decreasing gap size of the annuli and described the importance of the thin film evaporation to explain the lower CHF of narrow crevices. The effect of the inclination angle on the CHF on countercurrent boiling in an inclined uniformly heated tube with closed bottoms was also studied by Liu et al. They concluded that the CHF reduced with the inclination angle decrease. A study was carried out

  13. Glutamate Transporters in the Blood-Brain Barrier

    DEFF Research Database (Denmark)

    Helms, Hans Christian Cederberg; Nielsen, Carsten Uhd; Waagepetersen, Helle S

    2017-01-01

    concentration of L-glutamate causes excitotoxicity. A tight control of the brain interstitial fluid L-glutamate levels is therefore imperative, in order to maintain optimal neurotransmission and to avoid such excitotoxicity. The blood-brain barrier, i.e., the endothelial lining of the brain capillaries...... cells. The mechanisms underlying transendothelial L-glutamate transport are however still not well understood. The present chapter summarizes the current knowledge on blood-brain barrier L-glutamate transporters and the suggested pathways for the brain-to-blood L-glutamate efflux......., regulates the exchange of nutrients, gases, and metabolic waste products between plasma and brain interstitial fluid. It has been suggested that brain capillary endothelial cells could play an important role in L-glutamate homeostasis by mediating brain-to-blood L-glutamate efflux. Both in vitro and in vivo...

  14. Nanofiber mat spinal cord dressing-released glutamate impairs blood-spinal cord barrier

    Directory of Open Access Journals (Sweden)

    Dorota Sulejczak

    2016-12-01

    Full Text Available An excessive glutamate level can result in excitotoxic damage and death of central nervous system (CNS cells, and is involved in the pathogenesis of many CNS diseases. It may also be related to a failure of the blood-spinal cord barrier (BSCB. This study was aimed at examining the effects of extended administration of monosodium glutamate on the BSCB and spinal cord cells in adult male Wistar rats. The glutamate was delivered by subarachnoidal application of glutamate-carrying electrospun nanofiber mat dressing at the lumbar enlargement level. Half of the rats with the glutamate-loaded mat application were treated systemically with the histone deacetylase inhibitor valproic acid. A group of intact rats and a rat group with subarachnoidal application of an ‘empty’ (i.e., carrying no glutamate nanofiber mat dressing served as controls. All the rats were euthanized three weeks later and lumbar fragments of their spinal cords were harvested for histological, immunohistochemical and ultrastructural studies. The samples from controls revealed normal parenchyma and BSCB morphology, whereas those from rats with the glutamate-loaded nanofiber mat dressing showed many intraparenchymal microhemorrhages of variable sizes. The capillaries in the vicinity of the glutamate-carrying dressing (in the meninges and white matter alike were edematous and leaky, and their endothelial cells showed degenerative changes: extensive swelling, enhanced vacuo­lization and the presence of vascular intraluminal projections. However, endothelial tight junctions were generally well preserved. Some endothelial cells were dying by necrosis or apoptosis. The adjacent parenchyma showed astrogliosis with astrocytic hypertrophy and swelling of perivascular astrocytic feet. Neurons in the parenchyma revealed multiple symptoms of degeneration, including, inter alia, perikaryal, dendritic and axonal swelling, and destruction of organelles. All the damage symptoms were slightly less

  15. Effect of biotin on transcription levels of key enzymes and glutamate efflux in glutamate fermentation by Corynebacterium glutamicum.

    Science.gov (United States)

    Cao, Yan; Duan, Zuoying; Shi, Zhongping

    2014-02-01

    Biotin is an important factor affecting the performance of glutamate fermentation by biotin auxotrophic Corynebacterium glutamicum and glutamate is over-produced only when initial biotin content is controlled at suitable levels or initial biotin is excessive but with Tween 40 addition during fermentation. The transcription levels of key enzymes at pyruvate, isocitrate and α-ketoglutarate metabolic nodes, as well as transport protein (TP) of glutamate were investigated under the conditions of varied biotin contents and Tween 40 supplementation. When biotin was insufficient, the genes encoding key enzymes and TP were down-regulated in the early production phase, in particular, the transcription level of isocitrate dehydrogenase (ICDH) which was only 2% of that of control. Although the cells' morphology transformation and TP level were not affected, low transcription level of ICDH led to lower final glutamate concentration (64 g/L). When biotin was excessive, the transcription levels of key enzymes were at comparable levels as those of control with ICDH as an exception, which was only 3-22% of control level throughout production phase. In this case, little intracellular glutamate accumulation (1.5 mg/g DCW) and impermeable membrane resulted in non glutamate secretion into broth, even though the quantity of TP was more than 10-folds of control level. Addition of Tween 40 when biotin was excessive stimulated the expression of all key enzymes and TP, intracellular glutamate content was much higher (10-12 mg/g DCW), and final glutamate concentration reached control level (75-80 g/L). Hence, the membrane alteration and TP were indispensable in glutamate secretion. Biotin and Tween 40 influenced the expression level of ICDH and glutamate efflux, thereby influencing glutamate production.

  16. Enzymatic production of α-ketoglutaric acid from l-glutamic acid via l-glutamate oxidase.

    Science.gov (United States)

    Niu, Panqing; Dong, Xiaoxiang; Wang, Yuancai; Liu, Liming

    2014-06-10

    In this study, a novel strategy for α-ketoglutaric acid (α-KG) production from l-glutamic acid using recombinant l-glutamate oxidase (LGOX) was developed. First, by analyzing the molecular structure characteristics of l-glutamic acid and α-KG, LGOX was found to be the best catalyst for oxidizing the amino group of l-glutamic acid to a ketonic group without the need for exogenous cofactor. Then the LGOX gene was expressed in Escherichia coli BL21 (DE3) in a soluble and active form, and the recombinant LGOX activity reached to a maximum value of 0.59U/mL at pH 6.5, 30°C. Finally, the maximum α-KG concentration reached 104.7g/L from 110g/L l-glutamic acid in 24h, under the following optimum conditions: 1.5U/mL LGOX, 250U/mL catalase, 3mM MnCl2, 30°C, and pH 6.5. Copyright © 2014. Published by Elsevier B.V.

  17. Inhibition of the Mitochondrial Glutamate Carrier SLC25A22 in Astrocytes Leads to Intracellular Glutamate Accumulation

    Directory of Open Access Journals (Sweden)

    Emmanuelle Goubert

    2017-05-01

    Full Text Available The solute carrier family 25 (SLC25 drives the import of a large diversity of metabolites into mitochondria, a key cellular structure involved in many metabolic functions. Mutations of the mitochondrial glutamate carrier SLC25A22 (also named GC1 have been identified in early epileptic encephalopathy (EEE and migrating partial seizures in infancy (MPSI but the pathophysiological mechanism of GC1 deficiency is still unknown, hampered by the absence of an in vivo model. This carrier is mainly expressed in astrocytes and is the principal gate for glutamate entry into mitochondria. A sufficient supply of energy is essential for the proper function of the brain and mitochondria have a pivotal role in maintaining energy homeostasis. In this work, we wanted to study the consequences of GC1 absence in an in vitro model in order to understand if glutamate catabolism and/or mitochondrial function could be affected. First, short hairpin RNA (shRNA designed to specifically silence GC1 were validated in rat C6 glioma cells. Silencing GC1 in C6 resulted in a reduction of the GC1 mRNA combined with a decrease of the mitochondrial glutamate carrier activity. Then, primary astrocyte cultures were prepared and transfected with shRNA-GC1 or mismatch-RNA (mmRNA constructs using the Neon® Transfection System in order to target a high number of primary astrocytes, more than 64%. Silencing GC1 in primary astrocytes resulted in a reduced nicotinamide adenine dinucleotide (Phosphate (NAD(PH formation upon glutamate stimulation. We also observed that the mitochondrial respiratory chain (MRC was functional after glucose stimulation but not activated by glutamate, resulting in a lower level of cellular adenosine triphosphate (ATP in silenced astrocytes compared to control cells. Moreover, GC1 inactivation resulted in an intracellular glutamate accumulation. Our results show that mitochondrial glutamate transport via GC1 is important in sustaining glutamate homeostasis in

  18. The application of glutamic acid alpha-decarboxylase for the valorization of glutamic acid

    NARCIS (Netherlands)

    Lammens, T.M.; Biase, De Daniela; Franssen, M.C.R.; Scott, E.L.; Sanders, J.P.M.

    2009-01-01

    Glutamic acid is an important constituent of waste streams from biofuels production. It is an interesting starting material for the synthesis of nitrogen containing bulk chemicals, thereby decreasing the dependency on fossil fuels. On the pathway from glutamic acid to a range of molecules, the

  19. A role of the transcriptional regulator LldR (NCgl2814) in glutamate metabolism under biotin-limited conditions in Corynebacterium glutamicum.

    Science.gov (United States)

    Supkulsutra, Tanyanut; Maeda, Tomoya; Kumagai, Kosuke; Wachi, Masaaki

    2013-01-01

    Corynebacterium glutamicum is a Gram-positive, rod-shaped, aerobic bacterium used for the fermentative production of L-glutamate. LldR (NCgl2814) is known as a repressor for ldhA and lldD encoding lactate dehydrogenases. LdhA is responsible for production of L-lactate, while LldD is for its assimilation. Since L-lactate production was observed as a by-product of glutamate production under biotin-limited conditions, LldR might play a regulatory role in the glutamate metabolism. Here for the first time, we investigated effects of overproduction or deletion of LldR on the glutamate metabolism under biotin-limited conditions in C. glutamicum. It was found that glutamate production under biotin-limited conditions was decreased by overproduction of LldR. In the wild-type cells, L-lactate was produced in the first 24 h and it was re-consumed thereafter. On the other hand, in the overproduced cells, L-lactate was produced like the wild type, but it was not re-consumed. This means that L-lactate assimilation, which is catalyzed by LldD, was suppressed by the overproduction of LldR, but L-lactate production, which is catalyzed by LdhA, was not affected, indicating that LldR mainly controls the expression of lldD but not of ldhA under biotin-limited conditions. This was confirmed by quantitative real-time RT-PCR. From these results, it is suggested that L-lactate metabolism, which is controlled by LldR, has a buffering function of the pyruvate pool for glutamate production.

  20. PDA: Pooled DNA analyzer

    Directory of Open Access Journals (Sweden)

    Lin Chin-Yu

    2006-04-01

    Full Text Available Abstract Background Association mapping using abundant single nucleotide polymorphisms is a powerful tool for identifying disease susceptibility genes for complex traits and exploring possible genetic diversity. Genotyping large numbers of SNPs individually is performed routinely but is cost prohibitive for large-scale genetic studies. DNA pooling is a reliable and cost-saving alternative genotyping method. However, no software has been developed for complete pooled-DNA analyses, including data standardization, allele frequency estimation, and single/multipoint DNA pooling association tests. This motivated the development of the software, 'PDA' (Pooled DNA Analyzer, to analyze pooled DNA data. Results We develop the software, PDA, for the analysis of pooled-DNA data. PDA is originally implemented with the MATLAB® language, but it can also be executed on a Windows system without installing the MATLAB®. PDA provides estimates of the coefficient of preferential amplification and allele frequency. PDA considers an extended single-point association test, which can compare allele frequencies between two DNA pools constructed under different experimental conditions. Moreover, PDA also provides novel chromosome-wide multipoint association tests based on p-value combinations and a sliding-window concept. This new multipoint testing procedure overcomes a computational bottleneck of conventional haplotype-oriented multipoint methods in DNA pooling analyses and can handle data sets having a large pool size and/or large numbers of polymorphic markers. All of the PDA functions are illustrated in the four bona fide examples. Conclusion PDA is simple to operate and does not require that users have a strong statistical background. The software is available at http://www.ibms.sinica.edu.tw/%7Ecsjfann/first%20flow/pda.htm.

  1. 21 CFR 182.1045 - Glutamic acid.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Glutamic acid. 182.1045 Section 182.1045 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN....1045 Glutamic acid. (a) Product. Glutamic acid. (b) [Reserved] (c) Limitations, restrictions, or...

  2. Heat transfer from internally heated hemispherical pools

    International Nuclear Information System (INIS)

    Gabor, J.D.; Ellsion, P.G.; Cassulo, J.C.

    1980-01-01

    Experiments were conducted on heat transfer from internally heated ZnSO 4 -H 2 O pools to the walls of hemispherical containers. This experimental technique provides data for a heat transfer system that has to date been only theoretically treated. Three different sizes of copper hemispherical containers were used: 240, 280, 320 mm in diameter. The pool container served both as a heat transfer surface and as an electrode. The opposing electrode was a copper disk, 50 mm in diameter located at the top of the pool in the center. The top surface of the pool was open to the atmosphere

  3. Influence of Glutamic Acid on the Properties of Poly(xylitol glutamate sebacate Bioelastomer

    Directory of Open Access Journals (Sweden)

    Weifu Dong

    2013-11-01

    Full Text Available In order to further improve the biocompatibility of xylitol based poly(xylitol sebacate (PXS bioelastomer, a novel kind of amino acid based poly(xylitol glutamate sebacate (PXGS has been successfully prepared in this work by melt polycondensation of xylitol, N-Boc glutamic acid and sebacic acid. Differential scanning calorimetry (DSC results indicated the glass-transition temperatures could be decreased by feeding N-Boc glutamic acid. In comparison to PXS, PXGS exhibited comparable tensile strength and much higher elongation at break at the same ratio of acid/xylitol. The introduction of glutamic acid increased the hydrophilicity and in vitro degradation rate of the bioelastomer. It was found that PXGS exhibited excellent properties, such as tensile properties, biodegradability and hydrophilicity, which could be easily tuned by altering the feeding monomer ratios. The amino groups in the PXGS polyester side chains are readily functionalized, thus the biomelastomers can be considered as potential biomaterials for biomedical application.

  4. Microbial production of poly-γ-glutamic acid.

    Science.gov (United States)

    Sirisansaneeyakul, Sarote; Cao, Mingfeng; Kongklom, Nuttawut; Chuensangjun, Chaniga; Shi, Zhongping; Chisti, Yusuf

    2017-09-05

    Poly-γ-glutamic acid (γ-PGA) is a natural, biodegradable and water-soluble biopolymer of glutamic acid. This review is focused on nonrecombinant microbial production of γ-PGA via fermentation processes. In view of its commercial importance, the emphasis is on L-glutamic acid independent producers (i.e. microorganisms that do not require feeding with the relatively expensive amino acid L-glutamic acid to produce γ-PGA), but glutamic acid dependent production is discussed for comparison. Strategies for improving production, reducing costs and using renewable feedstocks are discussed.

  5. Cation-Size-Dependent Conformational Locking of Glutamic Acid by Alkali Ions: Infrared Photodissociation Spectroscopy of Cryogenic Ions.

    Science.gov (United States)

    Klyne, Johanna; Bouchet, Aude; Ishiuchi, Shun-Ichi; Fujii, Masaaki; Dopfer, Otto

    2018-03-01

    Consolidated knowledge of conformation and stability of amino acids and their clusters is required to understand their biochemical recognition. Often, alkali ions interact with amino acids and proteins. Herein, infrared photodissociation (IRPD) spectra of cryogenic metalated glutamic acid ions (GluM + , M = Li-Cs) are systematically analyzed in the isomer-specific fingerprint and XH stretch ranges (1100-1900, 2600-3600 cm -1 ) to provide a direct measure for cation-size-dependent conformational locking. GluM + ions are generated by electrospray ionization and cooled down to 15 K in a cryogenic quadrupole ion trap. The assignment of the IRPD spectra is supported by density functional theory calculations at the dispersion-corrected B3LYP-D3/aug-cc-pVTZ level. In the global minimum of GluM + , the flexibility of Glu is strongly reduced by the formation of rigid ionic CO···M + ···OC metal bridges, corresponding to charge solvation. The M + binding energy decreases monotonically with increasing cation size from D 0 = 314 to 119 kJ/mol for Li-Cs. Whereas for Li and Na only the global minimum of GluM + is observed, for K-Cs at least three isomers exist at cryogenic temperature. The IRPD spectra of cold GluM + ions are compared to IR multiple-photon dissociation spectra measured at room temperature. Furthermore, we elucidate the differences of the impact of protonation and metalation on the structure and conformational locking of Glu.

  6. Enhancing poly-γ-glutamic acid production in Bacillus amyloliquefaciens by introducing the glutamate synthesis features from Corynebacterium glutamicum.

    Science.gov (United States)

    Feng, Jun; Quan, Yufen; Gu, Yanyan; Liu, Fenghong; Huang, Xiaozhong; Shen, Haosheng; Dang, Yulei; Cao, Mingfeng; Gao, Weixia; Lu, Xiaoyun; Wang, Yi; Song, Cunjiang; Wang, Shufang

    2017-05-22

    Poly-γ-glutamic acid (γ-PGA) is a valuable polymer with glutamate as its sole precursor. Enhancement of the intracellular glutamate synthesis is a very important strategy for the improvement of γ-PGA production, especially for those glutamate-independent γ-PGA producing strains. Corynebacterium glutamicum has long been used for industrial glutamate production and it exhibits some unique features for glutamate synthesis; therefore introduction of these metabolic characters into the γ-PGA producing strain might lead to increased intracellular glutamate availability, and thus ultimate γ-PGA production. In this study, the unique glutamate synthesis features from C. glutamicum was introduced into the glutamate-independent γ-PGA producing Bacillus amyloliquefaciens NK-1 strain. After introducing the energy-saving NADPH-dependent glutamate dehydrogenase (NADPH-GDH) pathway, the NK-1 (pHT315-gdh) strain showed slightly increase (by 9.1%) in γ-PGA production. Moreover, an optimized metabolic toggle switch for controlling the expression of ɑ-oxoglutarate dehydrogenase complex (ODHC) was introduced into the NK-1 strain, because it was previously shown that the ODHC in C. glutamicum was completely inhibited when glutamate was actively produced. The obtained NK-PO1 (pHT01-xylR) strain showed 66.2% higher γ-PGA production than the NK-1 strain. However, the further combination of these two strategies (introducing both NADPH-GDH pathway and the metabolic toggle switch) did not lead to further increase of γ-PGA production but rather the resultant γ-PGA production was even lower than that in the NK-1 strain. We proposed new metabolic engineering strategies to improve the γ-PGA production in B. amyloliquefaciens. The NK-1 (pHT315-gdh) strain with the introduction of NADPH-GDH pathway showed 9.1% improvement in γ-PGA production. The NK-PO1 (pHT01-xylR) strain with the introduction of a metabolic toggle switch for controlling the expression of ODHC showed 66.2% higher

  7. Simulation of pool scrubbing experiments using BUSCA

    International Nuclear Information System (INIS)

    Dehbi, A.; Guentay, S.

    1994-01-01

    BUSCA-PSI is a computer code which predicts the aerosol scrubbing taking place when gas bubbles containing fission products rise through stagnant pools of water after a postulated severe accident. A Lagrangian formulation is adopted to follow the path of a bubble as it rises toward the surface of the pool. The BUSCA model includes most aerosol removal mechanisms which are thought to be significant, namely: Jet Impaction at tile orifice, Convection/Diffusiophoresis during steam condensation, Thermophoresis, Sedimentation, Centrifugal Impaction during bubble rise, and Brownian Diffusion. The hydraulic modelling offers a variety of options for the initial globule volume, the stable bubble size, tile bubble rise velocity, and the bubble shape. The heat and mass transfer part of tile model uses correlations found in the relevant literature. BUSCA simulations were performed to determine the decontamination factor (DF) dependence on key aerosol and thermal hydraulic parameters. The decontamination factor increases with height, pool temperature subcooling, and steam content. The decontamination factor exhibits a parabolic dependence on the particle radius. At low particle sizes, the DF is high due to Brownian Diffusion which is the dominant removal mechanism. The DF hits a minimum and then increases with particle size as Centrifugal Impaction and Sedimentation become important. In separate calculations, BUSCA was used to the simulate the aerosol scrubbing experiments performed by EPRI. For cold pool tests, the predicted scrubbing efficiencies were in a good, conservative agreement with the data for both Tin and CsI, and the discrepancies were within the reported measurement errors. For hot pool tests, the code systematically underpredicted the scrubbing DF's; this is potentially due to condensation in the gas space above the pool, a situation not currently modelled by BUSCA. The code was also tested against data produced by the Tepco-Toshiba-Hitachi experiments. The

  8. Deletion of glutamate dehydrogenase 1 (Glud1) in the central nervous system affects glutamate handling without altering synaptic transmission

    DEFF Research Database (Denmark)

    Frigerio, Francesca; Karaca, Melis; De Roo, Mathias

    2012-01-01

    Glutamate dehydrogenase (GDH), encoded by GLUD1, participates in the breakdown and synthesis of glutamate, the main excitatory neurotransmitter. In the CNS, besides its primary signaling function, glutamate is also at the crossroad of metabolic and neurotransmitter pathways. Importance of brain GDH...... was questioned here by generation of CNS-specific GDH-null mice (CnsGlud1(-/-)); which were viable, fertile and without apparent behavioral problems. GDH immunoreactivity as well as enzymatic activity were absent in Cns-Glud1(-/-) brains. Immunohistochemical analyses on brain sections revealed that the pyramidal...... oxidative catabolism of glutamate in astrocytes, showing that GDH is required for Krebs cycle pathway. As revealed by NMR studies, brain glutamate levels remained unchanged, whereas glutamine levels were increased. This pattern was favored by up-regulation of astrocyte-type glutamate and glutamine...

  9. Strontium D-Glutamate Hexahydrate and Strontium Di(hydrogen L-glutamate) Pentahydrate

    DEFF Research Database (Denmark)

    Christgau, Stephan; Odderhede, Jette; Stahl, Kenny

    2005-01-01

    Sr(C5H7NO4)] center dot 6H(2)O, ( I), and [Sr(C5H8NO4)(2)] center dot 5H(2)O, (II), both crystallize with similar strontium - glutamate - water layers. In ( I), the neutral layers are connected through hydrogen bonds by water molecules, while in ( II), the positively charged layers are connected...... through hydrogen bonds and electrostatic interactions by interleaving layers of hydrogen glutamate anions and water molecules....

  10. A radiometric microassay for glutamic acid decarboxylase

    International Nuclear Information System (INIS)

    Maderdrut, J.L.; North Carolina Univ., Chapel Hill

    1979-01-01

    A simple method for purifying L-[ 3 H] glutamic acid and incubation conditions suitable for estimating L-glutamic acid decarboxylase activity are described. Routine and recycled cation-exchange procedure for separating γ-aminobutyric acid from L-glutamate are outlined and compared. Recycling increases the sensitivity of the cation-exchange method by 6-7 fold. L-Glutamate decarboxylase activity can be measured reliably in samples of embryonic neural tissue having wet-weights of approximately 1 μg. The cation-exchange method is compared with the anion-exchange and CO 2 -trapping methods. L-Glutamate decarboxylase activity has been detected in the lumbar spinal cord of the chick embryo at Day 21/4 (stage 14) using the cation-exchange method. This is 5-6 days earlier than L-glutamate decarboxylase activity has been detected in embryonic neural tissue by previous investigators. L-Glutamate decarboxylase is present in the lumbar spinal cord at least as early as the birth of the first lumbar spinal cord neurons and at least 1-2 days before the initiation of synaptogenesis. (author)

  11. AMPK Activation Affects Glutamate Metabolism in Astrocytes

    DEFF Research Database (Denmark)

    Voss, Caroline Marie; Pajęcka, Kamilla; Stridh, Malin H

    2015-01-01

    acid (TCA) cycle was studied using high-performance liquid chromatography analysis supplemented with gas chromatography-mass spectrometry technology. It was found that AMPK activation had profound effects on the pathways involved in glutamate metabolism since the entrance of the glutamate carbon...... on glutamate metabolism in astrocytes was studied using primary cultures of these cells from mouse cerebral cortex during incubation in media containing 2.5 mM glucose and 100 µM [U-(13)C]glutamate. The metabolism of glutamate including a detailed analysis of its metabolic pathways involving the tricarboxylic...... skeleton into the TCA cycle was reduced. On the other hand, glutamate uptake into the astrocytes as well as its conversion to glutamine catalyzed by glutamine synthetase was not affected by AMPK activation. Interestingly, synthesis and release of citrate, which are hallmarks of astrocytic function, were...

  12. Sediment transport through self-adjusting, bedrock-walled waterfall plunge pools

    Science.gov (United States)

    Scheingross, Joel S.; Lamb, Michael P.

    2016-05-01

    Many waterfalls have deep plunge pools that are often partially or fully filled with sediment. Sediment fill may control plunge-pool bedrock erosion rates, partially determine habitat availability for aquatic organisms, and affect sediment routing and debris flow initiation. Currently, there exists no mechanistic model to describe sediment transport through waterfall plunge pools. Here we develop an analytical model to predict steady-state plunge-pool depth and sediment-transport capacity by combining existing jet theory with sediment transport mechanics. Our model predicts plunge-pool sediment-transport capacity increases with increasing river discharge, flow velocity, and waterfall drop height and decreases with increasing plunge-pool depth, radius, and grain size. We tested the model using flume experiments under varying waterfall and plunge-pool geometries, flow hydraulics, and sediment size. The model and experiments show that through morphodynamic feedbacks, plunge pools aggrade to reach shallower equilibrium pool depths in response to increases in imposed sediment supply. Our theory for steady-state pool depth matches the experiments with an R2 value of 0.8, with discrepancies likely due to model simplifications of the hydraulics and sediment transport. Analysis of 75 waterfalls suggests that the water depths in natural plunge pools are strongly influenced by upstream sediment supply, and our model provides a mass-conserving framework to predict sediment and water storage in waterfall plunge pools for sediment routing, habitat assessment, and bedrock erosion modeling.

  13. Fluorescence imaging of glutamate release in neurons

    International Nuclear Information System (INIS)

    Wang, Ziqiang; Yeung, Edward S.

    1999-01-01

    A noninvasive detection scheme based on glutamate dehydrogenase (GDH) enzymatic assay combined with microscopy was developed to measure the glutamate release in cultured cells from the central nervous system (CNS). The enzyme reaction is very specific and sensitive. The detection limit with charge-coupled device (CCD) imaging is down to μM levels of glutamate with reasonable response time (∼30 s). The standard glutamate test shows a linear response over 3 orders of magnitude, from μM to 0.1 mM range. The in vitro monitoring of glutamate release from cultured neuron cells demonstrated excellent spatial and temporal resolution. (c) 1999 Society for Applied Spectroscopy

  14. An unusual correlation between ppGpp pool size and rate of ribosome synthesis during partial pyrimidine starvation of Escherichia coli

    DEFF Research Database (Denmark)

    Vogel, Ulla; Pedersen, Steen; Jensen, Kaj Frank

    1991-01-01

    Escherichia coli was exposed to partial pyrimidine starvation by feeding a pyrBI strain orotate as the only pyrimidine source. Subsequently, differential rates of synthesis of rRNA and of a few ribosome-associated proteins as well as the pool sizes of nucleoside triphosphates and ppGpp were measu...

  15. Microscopic bubble behaviour in suppression pool during wetwell venting

    Science.gov (United States)

    Zablackaite, G.; Nagasaka, H.; Kikura, H.

    2017-10-01

    During a severe accident PCV failure should be avoided and fission products inside PCV should be confined as much as possible. In order to minimize FPs release, Wetwell venting is conducted by releasing steam-non-condensable gas mixture carrying FPs from the Drywell to Suppression Pool. Steam is condensed by subcooled water in the pool, and most of FPs are retained into water. The removal of FP in the water pool is referred to as “Pool Scrubbing effect”. Hydrodynamic parameters of bubbles have impact on pool scrubbing effect. However, there is only few data available to evaluate quantitatively the bubble behaviour under depressurization and/or thermal stratification conditions. Series of experiments were conducted to evaluate the influence of temperature distribution, non-condensable gas content and pressure in the Wetwell on bubble behaviour. Bubbles were visualized using High Speed Camera and adopting shadowgraphy technique. Applying Particle Tracking Velocimetry, bubble velocity and size distribution were obtained from recorded images. Experimental results show that with increasing suppression pool temperature, bubbles reaching the pool surface decreased in size and traveling velocity became slower. In pressurized wetwell, bubble behaviour was similar to that in the heated up suppression pool case, although bubble parameters were similar to the low temperature case. Higher air content induced water surface movement and bubbles were smaller due to break up.

  16. Laser weld process monitoring and control using chromatic filtering of thermal radiation from a weld pool

    International Nuclear Information System (INIS)

    Kim, Cheol Jung; Kim, Min Suk; Baik, Sung Hoon; Chung, Chin Man

    2000-06-01

    The application of high power Nd: YAG lasers for precision welding in industry has been growing quite fast these days in diverse areas such as the automobile, the electronics and the aerospace industries. These diverse applications also require the new developments for the precise control and the reliable process monitoring. Due to the hostile environment in laser welding, a remote monitoring is required. The present development relates in general to weld process monitoring techniques, and more particularly to improved methods and apparatus for real-time monitoring of thermal radiation of a weld pool to monitor a size variation and a focus shift of the weld pool for weld process control, utilizing the chromatic aberration of focusing lens or lenses. The monitoring technique of the size variation and the focus shift of a weld pool is developed by using the chromatic filtering of the thermal radiation from a weld pool. The monitoring of weld pool size variation can also be used to monitor the weld depth in a laser welding. Furthermore, the monitoring of the size variation of a weld pool is independent of the focus shift of a weld pool and the monitoring of the focus shift of a weld pool is independent of the size variation of a weld pool

  17. Laser weld process monitoring and control using chromatic filtering of thermal radiation from a weld pool

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Cheol Jung; Kim, Min Suk; Baik, Sung Hoon; Chung, Chin Man

    2000-06-01

    The application of high power Nd: YAG lasers for precision welding in industry has been growing quite fast these days in diverse areas such as the automobile, the electronics and the aerospace industries. These diverse applications also require the new developments for the precise control and the reliable process monitoring. Due to the hostile environment in laser welding, a remote monitoring is required. The present development relates in general to weld process monitoring techniques, and more particularly to improved methods and apparatus for real-time monitoring of thermal radiation of a weld pool to monitor a size variation and a focus shift of the weld pool for weld process control, utilizing the chromatic aberration of focusing lens or lenses. The monitoring technique of the size variation and the focus shift of a weld pool is developed by using the chromatic filtering of the thermal radiation from a weld pool. The monitoring of weld pool size variation can also be used to monitor the weld depth in a laser welding. Furthermore, the monitoring of the size variation of a weld pool is independent of the focus shift of a weld pool and the monitoring of the focus shift of a weld pool is independent of the size variation of a weld pool.

  18. Glutamate and Brain Glutaminases in Drug Addiction.

    Science.gov (United States)

    Márquez, Javier; Campos-Sandoval, José A; Peñalver, Ana; Matés, José M; Segura, Juan A; Blanco, Eduardo; Alonso, Francisco J; de Fonseca, Fernando Rodríguez

    2017-03-01

    Glutamate is the principal excitatory neurotransmitter in the central nervous system and its actions are related to the behavioral effects of psychostimulant drugs. In the last two decades, basic neuroscience research and preclinical studies with animal models are suggesting a critical role for glutamate transmission in drug reward, reinforcement, and relapse. Although most of the interest has been centered in post-synaptic glutamate receptors, the presynaptic synthesis of glutamate through brain glutaminases may also contribute to imbalances in glutamate homeostasis, a key feature of the glutamatergic hypothesis of addiction. Glutaminases are the main glutamate-producing enzymes in brain and dysregulation of their function have been associated with neurodegenerative diseases and neurological disorders; however, the possible implication of these enzymes in drug addiction remains largely unknown. This mini-review focuses on brain glutaminase isozymes and their alterations by in vivo exposure to drugs of abuse, which are discussed in the context of the glutamate homeostasis theory of addiction. Recent findings from mouse models have shown that drugs induce changes in the expression profiles of key glutamatergic transmission genes, although the molecular mechanisms that regulate drug-induced neuronal sensitization and behavioral plasticity are not clear.

  19. Chitosan Glutamate-Coated Niosomes: A Proposal for Nose-to-Brain Delivery

    Directory of Open Access Journals (Sweden)

    Federica Rinaldi

    2018-03-01

    Full Text Available The aim of this in vitro study is to prepare and characterize drug free and pentamidine loaded chitosan glutamate coated niosomes for intranasal drug delivery to reach the brain through intranasal delivery. Mucoadhesive properties and stability testing in various environments were evaluated to examine the potential of these formulations to be effective drug delivery vehicles for intranasal delivery to the brain. Samples were prepared using thin film hydration method. Changes in size and ζ-potential of coated and uncoated niosomes with and without loading of pentamidine in various conditions were assessed by dynamic light scattering (DLS, while size and morphology were also studied by atomic force microscopy (AFM. Bilayer properties and mucoadhesive behavior were investigated by fluorescence studies and DLS analyses, respectively. Changes in vesicle size and ζ-potential values were shown after addition of chitosan glutamate to niosomes, and when in contact with mucin solution. In particular, interactions with mucin were observed in both drug free and pentamidine loaded niosomes regardless of the presence of the coating. The characteristics of the proposed systems, such as pentamidine entrapment and mucin interaction, show promising results to deliver pentamidine or other possible drugs to the brain via nasal administration.

  20. Fabrication of Implantable, Enzyme-Immobilized Glutamate Sensors for the Monitoring of Glutamate Concentration Changes in Vitro and in Vivo

    Directory of Open Access Journals (Sweden)

    Tina T.-C. Tseng

    2014-06-01

    Full Text Available Glutamate sensors based on the immobilization of glutamate oxidase (GlutOx were prepared by adsorption on electrodeposited chitosan (Method 1 and by crosslinking with glutaraldehyde (Method 2 on micromachined platinum microelectrodes. It was observed that glutamate sensors prepared by Method 1 have faster response time (<2 s and lower detection limit (2.5 ± 1.1 μM compared to that prepared by Method 2 (response time: <5 sec and detection limit: 6.5 ± 1.7 μM; glutamate sensors prepared by Method 2 have a larger linear detection range (20–352 μM and higher sensitivity (86.8 ± 8.8 nA·μM−1·cm−2, N = 12 compared to those prepared by Method 1 (linear detection range: 20–217 μM and sensitivity: 34.9 ± 4.8 nA·μM−1·cm−2, N = 8. The applicability of the glutamate sensors in vivo was also demonstrated. The glutamate sensors were implanted into the rat brain to monitor the stress-induced extracellular glutamate release in the hypothalamus of the awake, freely moving rat.

  1. 21 CFR 182.1047 - Glutamic acid hydrochloride.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Glutamic acid hydrochloride. 182.1047 Section 182.1047 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... Food Substances § 182.1047 Glutamic acid hydrochloride. (a) Product. Glutamic acid hydrochloride. (b...

  2. Diets high in resistant starch and arabinoxylan modulate digestion processes and SCFA pool size in the large intestine and faecal microbial composition in pigs.

    Science.gov (United States)

    Nielsen, Tina S; Lærke, Helle N; Theil, Peter K; Sørensen, Jens F; Saarinen, Markku; Forssten, Sofia; Knudsen, Knud E Bach

    2014-12-14

    The effects of a high level of dietary fibre (DF) either as arabinoxylan (AX) or resistant starch (RS) on digestion processes, SCFA concentration and pool size in various intestinal segments and on the microbial composition in the faeces were studied in a model experiment with pigs. A total of thirty female pigs (body weight 63.1 (sem 4.4) kg) were fed a low-DF, high-fat Western-style control diet (WSD), an AX-rich diet (AXD) or a RS-rich diet (RSD) for 3 weeks. Diet significantly affected the digestibility of DM, protein, fat, NSP and NSP components, and the arabinose:xylose ratio, as well as the disappearance of NSP and AX in the large intestine. RS was mainly digested in the caecum. AX was digested at a slower rate than RS. The digesta from AXD-fed pigs passed from the ileum to the distal colon more than twice as fast as those from WSD-fed pigs, with those from RSD-fed pigs being intermediate (PEubacterium rectale, Bifidobacterium spp. and Lactobacillus spp. in the faeces sampled at week 3 of the experimental period (P< 0.05). In the caecum, proximal and mid colon, AXD feeding resulted in a 3- to 5-fold higher pool size of butyrate compared with WSD feeding, with the RSD being intermediate (P <0.001). In conclusion, the RSD and AXD differently affected digestion processes compared with the WSD, and the AXD most efficiently shifted the microbial composition towards butyrogenic species in the faeces and increased the large-intestinal butyrate pool size.

  3. Glutamate mechanisms underlying opiate memories

    NARCIS (Netherlands)

    Peters, J.; de Vries, T.J.

    2012-01-01

    As the major excitatory neurotransmitter in the brain, glutamate plays an undisputable integral role in opiate addiction. This relates, in part, to the fact that addiction is a disorder of learning and memory, and glutamate is required for most types of memory formation. As opiate addiction

  4. The role of glutamate and its receptors in autism and the use of glutamate receptor antagonists in treatment

    Science.gov (United States)

    Rojas, Donald C.

    2014-01-01

    Glutamate is the major excitatory neurotransmitter in the brain and may be a key neurotransmitter involved in autism. Literature pertaining to glutamate and autism or related disorders (e.g., Fragile X syndrome) is reviewed in this article. Interest in glutamatergic dysfunction in autism is high due to increasing convergent evidence implicating the system in the disorder from peripheral biomarkers, neuroimaging, protein expression, genetics and animal models. Currently, there are no pharmaceutical interventions approved for autism that address glutamate deficits in the disorder. New treatments related to glutamatergic neurotransmission, however, are emerging. In addition, older glutamate-modulating medications with approved indications for use in other disorders are being investigated for re-tasking as treatments for autism. This review presents evidence in support of glutamate abnormalities in autism and the potential for translation into new treatments for the disorder. PMID:24752754

  5. Influence of the glutamic acid content of the diet on the catabolic rate of labelled glutamic acid in rats. 2

    International Nuclear Information System (INIS)

    Wilke, A.; Simon, O.; Bergner, H.

    1984-01-01

    40 rats with a body weight of 100 g received 7 semisynthetic diets with different contents of glutamic acid and one diet contained whole-egg. A L-amino acid mixture corresponding to the pattern of egg protein was the protein source of the semisynthetic diets. Glutamic acid was supplemented succesively from 0 to 58 mol-% of the total amino acid content. On the 8th day of the experimental feeding the animals were labelled by subcutaneous injection of 14 C-glutamic acid. Subsequently the CO 2 and the 14 CO 2 excretion were measured for 24 hours. In this period 64 to 68 % of the injected radioactivity were recovered as 14 CO 2 . The curve pattern of 14 CO 2 excretion indicates two different processes of 14 CO 2 formation. One characterizing the direct degradation of glutamic acid to CO 2 with a high rate constant and a second one with a lower rate constant characterizing the 14 CO 2 formation via metabolites of glutamic acid. 77 % of the total 14 CO 2 excretion in 24 hours resulted from the direct oxidation of glutamic acid and 23 % from the oxidation of intermediates. When 14 CO 2 formation was measured 10 to 24 hours after injection of 14 C-glutamic acid a positive correlation to the content of glutamic acid in the diet was observed. The intestinal tissue contributes considerably to the catabolization of glutamic acid, however, there seems to exist an upper limit for this capacity. (author)

  6. Aspartate and glutamate mimetic structures in biologically active compounds.

    Science.gov (United States)

    Stefanic, Peter; Dolenc, Marija Sollner

    2004-04-01

    Glutamate and aspartate are frequently recognized as key structural elements for the biological activity of natural peptides and synthetic compounds. The acidic side-chain functionality of both the amino acids provides the basis for the ionic interaction and subsequent molecular recognition by specific receptor sites that results in the regulation of physiological or pathophysiological processes in the organism. In the development of new biologically active compounds that possess the ability to modulate these processes, compounds offering the same type of interactions are being designed. Thus, using a peptidomimetic design approach, glutamate and aspartate mimetics are incorporated into the structure of final biologically active compounds. This review covers different bioisosteric replacements of carboxylic acid alone, as well as mimetics of the whole amino acid structure. Amino acid analogs presented include those with different distances between anionic moieties, and analogs with additional functional groups that result in conformational restriction or alternative interaction sites. The article also provides an overview of different cyclic structures, including various cycloalkane, bicyclic and heterocyclic analogs, that lead to conformational restriction. Higher di- and tripeptide mimetics in which carboxylic acid functionality is incorporated into larger molecules are also reviewed. In addition to the mimetic structures presented, emphasis in this article is placed on their steric and electronic properties. These mimetics constitute a useful pool of fragments in the design of new biologically active compounds, particularly in the field of RGD mimetics and excitatory amino acid agonists and antagonists.

  7. Time-resolved transcriptome analysis of Bacillus subtilis responding to valine, glutamate, and glutamine.

    Directory of Open Access Journals (Sweden)

    Bang-Ce Ye

    Full Text Available Microorganisms can restructure their transcriptional output to adapt to environmental conditions by sensing endogenous metabolite pools. In this paper, an Agilent customized microarray representing 4,106 genes was used to study temporal transcript profiles of Bacillus subtilis in response to valine, glutamate and glutamine pulses over 24 h. A total of 673, 835, and 1135 amino-acid-regulated genes were identified having significantly changed expression at one or more time points in response to valine, glutamate, and glutamine, respectively, including genes involved in cell wall, cellular import, metabolism of amino-acids and nucleotides, transcriptional regulation, flagellar motility, chemotaxis, phage proteins, sporulation, and many genes of unknown function. Different amino acid treatments were compared in terms of both the global temporal profiles and the 5-minute quick regulations, and between-experiment differential genes were identified. The highlighted genes were analyzed based on diverse sources of gene functions using a variety of computational tools, including T-profiler analysis, and hierarchical clustering. The results revealed the common and distinct modes of action of these three amino acids, and should help to elucidate the specific signaling mechanism of each amino acid as an effector.

  8. Chronic glutamate toxicity in neurodegenerative diseases-what is the evidence?

    Directory of Open Access Journals (Sweden)

    Pamela eMaher

    2015-12-01

    Full Text Available Together with aspartate, glutamate is the major excitatory neurotransmitter in the brain. Glutamate binds and activates both ligand-gated ion channels (ionotropic glutamate receptors and a class of G-protein coupled receptors (metabotropic glutamate receptors. Although the intracellular glutamate concentration in the brain is in the millimolar range, the extracellular glutamate concentration is kept in the low micromolar range by the action of excitatory amino acid transporters that import glutamate and aspartate into astrocytes and neurons. Excess extracellular glutamate may lead to excitotoxicity in vitro and in vivo in acute insults like ischemic stroke via the overactivation of ionotropic glutamate receptors. In addition, chronic excitotoxicity has been hypothesized to play a role in numerous neurodegenerative diseases including amyotrophic lateral sclerosis, Alzheimer’s disease and Huntington’s disease. Based on this hypothesis, a good deal of effort has been devoted to develop and test drugs that either inhibit glutamate receptors or decrease extracellular glutamate. In this review, we provide an overview of the different pathways that are thought to lead to an over-activation of the glutamatergic system and glutamate toxicity in neurodegeneration. In addition, we summarize the available experimental evidence for glutamate toxicity in animal models of neurodegenerative diseases.

  9. Functional Comparison of the Two Bacillus anthracis Glutamate Racemases▿

    OpenAIRE

    Dodd, Dylan; Reese, Joseph G.; Louer, Craig R.; Ballard, Jimmy D.; Spies, M. Ashley; Blanke, Steven R.

    2007-01-01

    Glutamate racemase activity in Bacillus anthracis is of significant interest with respect to chemotherapeutic drug design, because l-glutamate stereoisomerization to d-glutamate is predicted to be closely associated with peptidoglycan and capsule biosynthesis, which are important for growth and virulence, respectively. In contrast to most bacteria, which harbor a single glutamate racemase gene, the genomic sequence of B. anthracis predicts two genes encoding glutamate racemases, racE1 and rac...

  10. Glutamate and GABA-metabolizing enzymes in post-mortem cerebellum in Alzheimer's disease: phosphate-activated glutaminase and glutamic acid decarboxylase.

    Science.gov (United States)

    Burbaeva, G Sh; Boksha, I S; Tereshkina, E B; Savushkina, O K; Prokhorova, T A; Vorobyeva, E A

    2014-10-01

    Enzymes of glutamate and GABA metabolism in postmortem cerebellum from patients with Alzheimer's disease (AD) have not been comprehensively studied. The present work reports results of original comparative study on levels of phosphate-activated glutaminase (PAG) and glutamic acid decarboxylase isoenzymes (GAD65/67) in autopsied cerebellum samples from AD patients and matched controls (13 cases in each group) as well as summarizes published evidence for altered levels of PAG and GAD65/67 in AD brain. Altered (decreased) levels of these enzymes and changes in links between amounts of these enzymes and other glutamate-metabolizing enzymes (such as glutamate dehydrogenase and glutamine synthetase-like protein) in AD cerebella suggest significantly impaired glutamate and GABA metabolism in this brain region, which was previously regarded as not substantially involved in AD pathogenesis.

  11. Delineation of glutamate pathways and secretory responses in pancreatic islets with ß-cell-specific abrogation of the glutamate dehydrogenase

    DEFF Research Database (Denmark)

    Vetterli, Laurene; Carobbio, Stefania; Pournourmohammadi, Shirin

    2012-01-01

    isolated from βGlud1(-/-) mice exhibited half of the response measured in control islets. The amplifying pathway, tested at stimulatory glucose concentrations in the presence of KCl and diazoxide, was markedly inhibited in βGlud1(-/-) islets. On glucose stimulation, net synthesis of glutamate from α......-ketoglutarate was impaired in GDH-deficient islets. Accordingly, glucose-induced elevation of glutamate levels observed in control islets was absent in βGlud1(-/-) islets. Parallel biochemical pathways, namely alanine and aspartate aminotransferases, could not compensate for the lack of GDH. However, the secretory response...... to glucose was fully restored by the provision of cellular glutamate when βGlud1(-/-) islets were exposed to dimethyl glutamate. This shows that permissive levels of glutamate are required for the full development of glucose-stimulated insulin secretion and that GDH plays an indispensable role...

  12. Mutual diffusion coefficients of L-glutamic acid and monosodium L-glutamate in aqueous solutions at T = 298.15 K

    International Nuclear Information System (INIS)

    Ribeiro, Ana C.F.; Rodrigo, M.M.; Barros, Marisa C.F.; Verissimo, Luis M.P.; Romero, Carmen; Valente, Artur J.M.; Esteso, Miguel A.

    2014-01-01

    Highlights: • Interdiffusion coefficients of L-glutamic acid and sodium L-glutamate were measured. • The L-glutamic acid behaves as a monoprotic weak acid. • The sodium L-glutamate shows a symmetrical 1:1 non-associated behaviour. • Limiting diffusion coefficients and ionic conductivities were estimated. • Diffusion coefficients were discussed on the basis of the Onsager–Fuoss equations. - Abstract: Mutual diffusion coefficient values for binary aqueous solutions of both L-glutamic acid (H 2 Glu) and sodium L-glutamate (NaHGlu) were measured with the Taylor dispersion technique, at T = 298.15 K, and concentrations ranging from (0.001 to 0.100) mol · dm −3 . The results were discussed on the basis of the Onsager–Fuoss and the Nernst theoretical equations, by considering the H 2 Glu as a weak acid (monoprotic acid, with K 2 = 5.62 · 10 −5 ). The smaller values found for the acid with respect to those of the salt, confirm this association hypothesis. From the diffusion coefficient values at infinitesimal concentration, limiting ionic conductivities as well as the hydrodynamic radius of the hydrogen glutamate ion (HGlu − ) were derived and analyzed in terms of the chain methylene groups. The effect of different phenomena, such as association or complexation, were also taken into consideration and discussed. Values for the dissociation degree for H 2 Glu were also estimated

  13. Pool scrubbing and hydrodynamic experiments on jet injection regime

    International Nuclear Information System (INIS)

    Peyres, V.; Espigares, M.M.; Polo, J.; Escudero, M.J.; Herranz, L.E.; Lopez-Jimenez, J.

    1995-01-01

    Plant analyses have shown that pool scrubbing can play an important role in source term during PWR risk dominant sequences. An examination ofboundary conditions governing fission products and aerosols transport through aqueous beds revealed that most of radioactivity is discharged into the pool under jet injection regime. This fact and the lack of experimental data under such conditions pointed the need of setting out an experimental programme which provided reliable experimental data to validate code models. In this report the major results of a pool scrubbing experimental programme carried out in PECA facility are presented. One of the major findings was that a remarkable fraction of particle absorption was not a function of the residence time of bubbles rising through the pool. Such a contribution was assumed to be associated to aerosol removal mechanisms acting at the pool entrance. As a consequence, a hydrodynamic experimental plan was launched to examine the gas behaviour during the initial stages in the pool. Size and shape of gas nuclei the pool were measured and fitted to a long normal distribution. Particularly, size was found to be quite sensitive to inletgas flow and at minor extent to gas composition and pool temperature. SPARC90 and BUSCA-AUG92 were used to simulate the retention tests. Whereas SPARC90 showed a pretty good agreement with experimental data, BUSCA-AUG92 results were far away from measurements in all the cases. SPARC90consistency apparently pointed out the important role of fission products and aerosols retention at the injection zone; nonetheless, a peer examination of pool scrubbing phenomenology at the pool entrance should be carried out to test both hydrodynamic and removal models. Hence, one of the major highlights drawn from this work was the need of further research under representative severe accident conditions (i.e., saturated pools, jet injection regimes, etc.), as well as separate effect tests to validate, improve and

  14. Pool scrubbing and hydrodynamic experiment on jet injection regime

    Energy Technology Data Exchange (ETDEWEB)

    Peyres, V.; Espigares, M.M.; Polo, J.; Escudero, M.J.; Herranz, L.E.; Lopez, J.

    1995-07-01

    Plant analyses nave shown that pool scrubbing can play an important role in source term during PWR risk dominant sequences. An examination of boundary conditions governing fission products and aerosols transport through aqueous beds revealed that most of radioactivity is discharged into the pool under jet injection regime. This fact and the lack of experimental data under such conditions pointed the need of setting out an experimental programme which provided reliable experimental data to validate code models. In this report the major results of a pool scrubbing experimental programme carried out in PECA facility are presented. One of the major findings was that a remarkable fraction of particle absorption was not a function of the residence time of bubbles rising through the pool. Such a contribution was assumed to be associated to aerosol removal mechanism acting at the pool entrance. As a consequence. a hydrodynamic experimental plan was launched to examine the gas behaviour during the initial stages in the pool. Size and shape of gas nuclei in the pool were measured and fitted to a lognormal distribution. Particularly, size was found to be quite sensitive to inlet gas flow and at minor extent to gas composition and pool temperature. SPARC90 and BUSCA-AUG92 were used to simulate the retention tests. Whereas SPARC90 showed a pretty good agreement with experimental data, BUSCA-AUG92 results were far away from measurements in all the cases. SPARC90 consistency apparently pointed out the important role of fission products and aerosols retention at the injection zone; nonetheless, a peer examination of pool scrubbing phenomenology at the pool entrance should be carried out to test both hydrodynamic and removal models. Hence, one of the major high lights drawn from this work was the need of further research under representative severe accident conditions (i.e., saturated pools, jet injection regimes, etc.), as well as separate effect tests to validate, improve and

  15. Pool scrubbing and hydrodynamic experiment on jet injection regime

    International Nuclear Information System (INIS)

    Peyres, V.; Espigares, M.M.; Polo, J.; Escudero, M.J.; Herranz, L.E.; Lopez, J.

    1995-01-01

    Plant analyses nave shown that pool scrubbing can play an important role in source term during PWR risk dominant sequences. An examination of boundary conditions governing fission products and aerosols transport through aqueous beds revealed that most of radioactivity is discharged into the pool under jet injection regime. This fact and the lack of experimental data under such conditions pointed the need of setting out an experimental programme which provided reliable experimental data to validate code models. In this report the major results of a pool scrubbing experimental programme carried out in PECA facility are presented. One of the major findings was that a remarkable fraction of particle absorption was not a function of the residence time of bubbles rising through the pool. Such a contribution was assumed to be associated to aerosol removal mechanism acting at the pool entrance. As a consequence. a hydrodynamic experimental plan was launched to examine the gas behaviour during the initial stages in the pool. Size and shape of gas nuclei in the pool were measured and fitted to a lognormal distribution. Particularly, size was found to be quite sensitive to inlet gas flow and at minor extent to gas composition and pool temperature. SPARC90 and BUSCA-AUG92 were used to simulate the retention tests. Whereas SPARC90 showed a pretty good agreement with experimental data, BUSCA-AUG92 results were far away from measurements in all the cases. SPARC90 consistency apparently pointed out the important role of fission products and aerosols retention at the injection zone; nonetheless, a peer examination of pool scrubbing phenomenology at the pool entrance should be carried out to test both hydrodynamic and removal models. Hence, one of the major high lights drawn from this work was the need of further research under representative severe accident conditions (i.e., saturated pools, jet injection regimes, etc.), as well as separate effect tests to validate, improve and

  16. Thermal analyses of solar swimming pool heating in Pakistan

    International Nuclear Information System (INIS)

    Ahmad, I.

    2011-01-01

    Hotels and swimming clubs in Pakistan pay huge gas bills for heating Swimming pools in winter. Winter days in most parts of Pakistan remain sunny and unglazed low cost solar collectors may be used to extend the swimming season. Installing the pool in a wind-protected area, which receives unobstructed solar radiation, may further reduce the size of the solar collectors required to heat the swimming pools. The pools should be covered with plastic sheet to eliminate evaporative heat losses and to prevent dust and tree leaves falling in the pool. The results of the thermal analysis show that in some parts of the country, a solar exposed pool can maintain comfortable temperature simply by using a plastic sheet on the pool surface. On the other hand, there are cities where solar collector array equal to twice the surface area of the pool is required to keep desired temperature in winter. (author)

  17. The Influence of Glutamate on Axonal Compound Action Potential In Vitro.

    Science.gov (United States)

    Abouelela, Ahmed; Wieraszko, Andrzej

    2016-01-01

    Background  Our previous experiments demonstrated modulation of the amplitude of the axonal compound action potential (CAP) by electrical stimulation. To verify assumption that glutamate released from axons could be involved in this phenomenon, the modification of the axonal CAP induced by glutamate was investigated. Objectives  The major objective of this research is to verify the hypothesis that axonal activity would trigger the release of glutamate, which in turn would interact with specific axonal receptors modifying the amplitude of the action potential. Methods  Segments of the sciatic nerve were exposed to exogenous glutamate in vitro, and CAP was recorded before and after glutamate application. In some experiments, the release of radioactive glutamate analog from the sciatic nerve exposed to exogenous glutamate was also evaluated. Results  The glutamate-induced increase in CAP was blocked by different glutamate receptor antagonists. The effect of glutamate was not observed in Ca-free medium, and was blocked by antagonists of calcium channels. Exogenous glutamate, applied to the segments of sciatic nerve, induced the release of radioactive glutamate analog, demonstrating glutamate-induced glutamate release. Immunohistochemical examination revealed that axolemma contains components necessary for glutamatergic neurotransmission. Conclusion  The proteins of the axonal membrane can under the influence of electrical stimulation or exogenous glutamate change membrane permeability and ionic conductance, leading to a change in the amplitude of CAP. We suggest that increased axonal activity leads to the release of glutamate that results in changes in the amplitude of CAPs.

  18. Modeling of glutamate-induced dynamical patterns

    DEFF Research Database (Denmark)

    Faurby-Bentzen, Christian Krefeld; Zhabotinsky, A.M.; Laugesen, Jakob Lund

    2009-01-01

    Based on established physiological mechanisms, the paper presents a detailed computer model, which supports the hypothesis that temporal lobe epilepsy may be caused by failure of glutamate reuptake from the extracellular space. The elevated glutamate concentration causes an increased activation...

  19. Microbial methodological artifacts in [3H]glutamate receptor binding assays

    International Nuclear Information System (INIS)

    Yoneda, Y.; Ogita, K.

    1989-01-01

    Incubation of radiolabeled L-glutamic acid, a putative central excitatory neurotransmitter, in 50 mM Tris-acetate buffer (pH 7.4) at 30 degrees C in the absence of brain synaptic membranes resulted in a significant adsorption of the radioactivity to glass fiber filters routinely employed to trap the bound ligand in receptor binding assays. The adsorption was not only eliminated by the inclusion of L-isomers of structurally related amino acids, but also inhibited by that of most presumed agonists and antagonists for the brain glutamate receptors. This displaceable adsorption was a temperature-dependent nonreversible, and saturable phenomenon. Scatchard analysis of these data revealed that the adsorption consisted of a single component with an apparent dissociation constant of 73 nM. The displaceable adsorption was significantly attenuated by a concurrent incubation with papain, pronase E, and phospholipase C. A significant amount of the radioactivity was detected in the pass-through fraction of the Dowex column following an application of the reaction mixture incubated with purified [ 3 H]glutamate at 30 degree C for 60 min in the absence of membranous proteins added. Complete abolition of the displaceable adsorption resulted from the use of incubation buffer boiled at 100 degrees C as well as filtered through a nitrocellulose membrane filter with a pore size of 0.45 micron immediately before use. These results suggest that the displaceable adsorption may be attributable to the radioactive metabolite of [ 3 H]glutamate by microorganisms contaminating the Tris-acetate buffer. This might in part contribute to some of the controversial results with regard to receptor binding studies on acidic amino acids

  20. PRELIMINARY STUDY OF FISH CULTURE IN ABANDONED SAND MINING POOL

    Directory of Open Access Journals (Sweden)

    Bambang Gunadi

    2006-12-01

    Full Text Available One of main problems in freshwater aquaculture development in Indonesia, especially in Java, is unavailability of developing zone. It is important to find an underutilized area that meets for industrial scale freshwater aquaculture, i.e. sufficient water supply, wide area, and located in one area or zone. The abandoned mining (sand, tin, etc. pools distributed along the country might be the potential area for freshwater aquaculture business. For example, there are at least 13 water pools with total surface area of 250 ha at 15 km side of Citarum River in Karawang District (West Java Province. This study was conducted to obtain preliminary data about the prospect and potency of fish culture (tilapia, clariid catfish, and ‘patin’ catfish in abandoned sand-mining pools in Karawang District. Mini floating net cages of 1 x 1 x 1.5 m3 size were used for culturing fish, i.e. patin catfish (Pangasianodon hypophthalmus, nile tilapia (Oreochromis niloticus, and clariid catfish (Clarias gariepinus, separately. Patin catfish were stocked at a size of 2 g with a density of 300 fish per cage, tilapia were stocked at a size of 6 g with a density of 400 fish per cage, while  the clariid catfish were stocked at a size of 1.4 g with a density of 980 fish per cage. A floating commercial feed (30%—32% protein, 3%—5% fat was used at a daily rate of 9% biomass weight at the beginning and reduced gradually to 3% at the final culture period. Observed data showed that patin catfish grew from the initial size of 2.08 g to the final size 299.59 g in 5 months, nile tilapia grew from individual initial size of 5.92 g to the final size of 247.12 g in 14 weeks, and clariid catfish grew from initial size of 1.39 g to the final size of 73.10 g in 8 weeks. These three species were technically prospective for aquaculture development in the abandoned sand-mining pools.

  1. SBWR PCCS vent phenomena and suppression pool mixing

    Energy Technology Data Exchange (ETDEWEB)

    Coddington, P. [Thermal-Hydraulics Lab., Paul Scherrer Institute, Villigen (Switzerland); Andreani, M. [Nuclear Engineering Lab., Swiss Federal Institute of Technology, Zurich (Switzerland)

    1995-09-01

    The most important phenomena influencing the effectiveness of the pressure suppression capability of the water pool within the Wetwell compartment of the SBWR Containment, during the period of Passive Containment Cooling System (PCCS) venting, have been critically reviewed. In addition, calculations have been carried-out to determine the condensation of the vented steam and the distribution of the energy deposited in the liquid pool. It has been found that a large contribution to the vapour suppression is due to condensation inside the vent pipe. The condensation rate of the steam inside the bubbles, produced at the vent exit, during their rise to the surface, may however be rather low, because of the large size bubbles. This can lead to vapour channelling to the Wetwell gas space. The above comments are likely to be ameliorated if the vent exit is a distributed source or sparger. Due to the large water flow rates within the {open_quotes}bubbly two-phase plume{close_quotes} generated by the gas injection, the water in the pool above the vent exit is likely to be heated nearly isothermally (perfect mixing). The effect of the suppression pool walls would be to enhance the recirculation and, consequently to promote mixing. The large size of the bubbles therein and of the walls on pool mixing are the most severe difficulties in extrapolating the results from scaled experiments to prototypical conditions.

  2. Single-Track Melt-Pool Measurements and Microstructures in Inconel 625

    Science.gov (United States)

    Ghosh, Supriyo; Ma, Li; Levine, Lyle E.; Ricker, Richard E.; Stoudt, Mark R.; Heigel, Jarred C.; Guyer, Jonathan E.

    2018-02-01

    We use single-track laser melting experiments and simulations on Inconel 625 to estimate the dimensions and microstructure of the resulting melt pool. Our work is based on a design-of-experiments approach which uses multiple laser power and scan speed combinations. Single-track experiments generated melt pools of certain dimensions that showed reasonable agreement with our finite-element calculations. Phase-field simulations were used to predict the size and segregation of the cellular microstructure that formed along the melt-pool boundaries for the solidification conditions that changed as a function of melt-pool dimensions.

  3. Single-Track Melt-Pool Measurements and Microstructures in Inconel 625

    Science.gov (United States)

    Ghosh, Supriyo; Ma, Li; Levine, Lyle E.; Ricker, Richard E.; Stoudt, Mark R.; Heigel, Jarred C.; Guyer, Jonathan E.

    2018-06-01

    We use single-track laser melting experiments and simulations on Inconel 625 to estimate the dimensions and microstructure of the resulting melt pool. Our work is based on a design-of-experiments approach which uses multiple laser power and scan speed combinations. Single-track experiments generated melt pools of certain dimensions that showed reasonable agreement with our finite-element calculations. Phase-field simulations were used to predict the size and segregation of the cellular microstructure that formed along the melt-pool boundaries for the solidification conditions that changed as a function of melt-pool dimensions.

  4. Poly (γ-glutamic acid)/beta-TCP nanocomposites via in situ copolymerization: Preparation and characterization.

    Science.gov (United States)

    Shu, Xiu-Lin; Shi, Qing-Shan; Feng, Jin; Yang, Yun-Hua; Zhou, Gang; Li, Wen-Ru

    2016-07-01

    A series biodegradable poly (γ-glutamic acid)/beta-tricalcium phosphate (γ-PGA/TCP) nanocomposites were prepared which were composed of poly-γ-glutamic acid polymerized in situ with β-tricalcium phosphate and physiochemically characterized as bone graft substitutes. The particle size via dynamic light scattering, the direct morphological characterization via transmission electron microscopy and field emission scanning electron microscope, which showed that γ-PGA and β-TCP were combined compactly at 80℃, and the γ-PGA/TCP nanocomposites had homogenous and nano-sized grains with narrow particle size distributions. The water uptake and retention abilities, in vitro degradation properties, cytotoxicity in the simulated medium, and protein release of these novel γ-PGA/TCP composites were investigated. Cell proliferation in composites was nearly twice than β-TCP when checked in vitro using MC3T3 cell line. We also envision the potential use of γ-PGA/TCP systems in bone growth factor or orthopedic drug delivery applications in future bone tissue engineering applications. These observations suggest that the γ-PGA/TCP are novel nanocomposites with great potential for application in the field of bone tissue engineering. © The Author(s) 2016.

  5. A Novel Corynebacterium glutamicum l-Glutamate Exporter.

    Science.gov (United States)

    Wang, Yu; Cao, Guoqiang; Xu, Deyu; Fan, Liwen; Wu, Xinyang; Ni, Xiaomeng; Zhao, Shuxin; Zheng, Ping; Sun, Jibin; Ma, Yanhe

    2018-03-15

    Besides metabolic pathways and regulatory networks, transport systems are also pivotal for cellular metabolism and hyperproduction of biochemicals using microbial cell factories. The identification and characterization of transporters are therefore of great significance for the understanding and engineering of transport reactions. Herein, a novel l-glutamate exporter, MscCG2, which exists extensively in Corynebacterium glutamicum strains but is distinct from the only known l-glutamate exporter, MscCG, was discovered in an industrial l-glutamate-producing C. glutamicum strain. MscCG2 was predicted to possess three transmembrane helices in the N-terminal region and located in the cytoplasmic membrane, which are typical structural characteristics of the mechanosensitive channel of small conductance. MscCG2 has a low amino acid sequence identity (23%) to MscCG and evolved separately from MscCG with four transmembrane helices. Despite the considerable differences between MscCG2 and MscCG in sequence and structure, gene deletion and complementation confirmed that MscCG2 also functioned as an l-glutamate exporter and an osmotic safety valve in C. glutamicum Besides, transcriptional analysis showed that MscCG2 and MscCG genes were transcribed in similar patterns and not induced by l-glutamate-producing conditions. It was also demonstrated that MscCG2-mediated l-glutamate excretion was activated by biotin limitation or penicillin treatment and that constitutive l-glutamate excretion was triggered by a gain-of-function mutation of MscCG2 (A151V). Discovery of MscCG2 will enrich the understanding of bacterial amino acid transport and provide additional targets for exporter engineering. IMPORTANCE The exchange of matter, energy, and information with surroundings is fundamental for cellular metabolism. Therefore, studying transport systems that are essential for these processes is of great significance. Besides, transport systems of bacterial cells are usually related to

  6. 13 CFR 120.611 - Pools backing Pool Certificates.

    Science.gov (United States)

    2010-01-01

    ... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Pools backing Pool Certificates. 120.611 Section 120.611 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION BUSINESS LOANS Secondary Market Certificates § 120.611 Pools backing Pool Certificates. (a) Pool characteristics. As set...

  7. Reduced expression of glutamate transporter EAAT2 and impaired glutamate transport in human primary astrocytes exposed to HIV-1 or gp120

    International Nuclear Information System (INIS)

    Wang Zhuying; Pekarskaya, Olga; Bencheikh, Meryem; Chao Wei; Gelbard, Harris A.; Ghorpade, Anuja; Rothstein, Jeffrey D.; Volsky, David J.

    2003-01-01

    L-Glutamate is the major excitatory neurotransmitter in the brain. Astrocytes maintain low levels of synaptic glutamate by high-affinity uptake and defects in this function may lead to neuronal cell death by excitotoxicity. We tested the effects of HIV-1 and its envelope glycoprotein gp120 upon glutamate uptake and expression of glutamate transporters EAAT1 and EAAT2 in fetal human astrocytes in vitro. Astrocytes isolated from fetal tissues between 16 and 19 weeks of gestation expressed EAAT1 and EAAT2 RNA and proteins as detected by Northern blot analysis and immunoblotting, respectively, and the cells were capable of specific glutamate uptake. Exposure of astrocytes to HIV-1 or gp120 significantly impaired glutamate uptake by the cells, with maximum inhibition within 6 h, followed by gradual decline during 3 days of observation. HIV-1-infected cells showed a 59% reduction in V max for glutamate transport, indicating a reduction in the number of active transporter sites on the cell surface. Impaired glutamate transport after HIV-1 infection or gp120 exposure correlated with a 40-70% decline in steady-state levels of EAAT2 RNA and protein. EAAT1 RNA and protein levels were less affected. Treatment of astrocytes with tumor necrosis factor-α (TNF-α) decreased the expression of both EAAT1 and EAAT2, but neither HIV-1 nor gp120 were found to induce TNF-α production by astrocytes. These findings demonstrate that HIV-1 and gp120 induce transcriptional downmodulation of the EAAT2 transporter gene in human astrocytes and coordinately attenuate glutamate transport by the cells. Reduction of the ability of HIV-1-infected astrocytes to take up glutamate may contribute to the development of neurological disease

  8. Glutamate. Its applications in food and contribution to health.

    Science.gov (United States)

    Jinap, S; Hajeb, P

    2010-08-01

    This article reviews application of glutamate in food and its benefits and role as one of the common food ingredients used. Monosodium glutamate is one of the most abundant naturally occurring amino acids which frequently added as a flavor enhancer. It produced a unique taste that cannot be provided by other basic taste (saltiness, sourness, sweetness and bitterness), referred to as a fifth taste (umami). Glutamate serves some functions in the body as well, serving as an energy source for certain tissues and as a substrate for glutathione synthesis. Glutamate has the potential to enhance food intake in older individuals and dietary free glutamate evoked a visceral sensation from the stomach, intestine and portal vein. Small quantities of glutamate used in combination with a reduced amount of table salt during food preparation allow for far less salt to be used during and after cooking. Because glutamate is one of the most intensely studied food ingredients in the food supply and has been found safe, the Joint Expert Committee on Food Additives of the United Nations Food and Agriculture Organization and World Health Organization placed it in the safest category for food additives. Despite a widespread belief that glutamate can elicit asthma, migraine headache and Chinese Restaurant Syndrome (CRS), there are no consistent clinical data to support this claim. In addition, findings from the literature indicate that there is no consistent evidence to suggest that individuals may be uniquely sensitive to glutamate. 2010 Elsevier Ltd. All rights reserved.

  9. Monte carlo simulation of vesicular release, spatiotemporal distribution of glutamate in synaptic cleft and generation of postsynaptic currents.

    Science.gov (United States)

    Glavinovíc, M I

    1999-02-01

    The release of vesicular glutamate, spatiotemporal changes in glutamate concentration in the synaptic cleft and the subsequent generation of fast excitatory postsynaptic currents at a hippocampal synapse were modeled using the Monte Carlo method. It is assumed that glutamate is released from a spherical vesicle through a cylindrical fusion pore into the synaptic cleft and that S-alpha-amino-3-hydroxy -5-methyl-4-isoxazolepropionic acid (AMPA) receptors are uniformly distributed postsynaptically. The time course of change in vesicular concentration can be described by a single exponential, but a slow tail is also observed though only following the release of most of the glutamate. The time constant of decay increases with vesicular size and a lower diffusion constant, and is independent of the initial concentration, becoming markedly shorter for wider fusion pores. The cleft concentration at the fusion pore mouth is not negligible compared to vesicular concentration, especially for wider fusion pores. Lateral equilibration of glutamate is rapid, and within approximately 50 micros all AMPA receptors on average see the same concentration of glutamate. Nevertheless the single-channel current and the number of channels estimated from mean-variance plots are unreliable and different when estimated from rise- and decay-current segments. Greater saturation of AMPA receptor channels provides higher but not more accurate estimates. Two factors contribute to the variability of postsynaptic currents and render the mean-variance nonstationary analysis unreliable, even when all receptors see on average the same glutamate concentration. Firstly, the variability of the instantaneous cleft concentration of glutamate, unlike the mean concentration, first rapidly decreases before slowly increasing; the variability is greater for fewer molecules in the cleft and is spatially nonuniform. Secondly, the efficacy with which glutamate produces a response changes with time. Understanding

  10. Influence of the glutamic acid content of the diet on the catabolisc rate of labelled glutamic acid in rats. 1

    International Nuclear Information System (INIS)

    Bergner, H.; Wilke, A.; Simon, O.; Wolf, E.

    1984-01-01

    Male rats received in 8 groups of 10 animals each for a period of 7 days 7 synthetic diets and one semisynthetic diet on maintenance requirement level. A L-amino acid mixture corresponding to the pattern of egg protein without glutamic acid was the protein source of the synthetic diets. Glutamic acid was supplemented successively from 0 to 58 mol-% of the total amino acid content. The crude protein source of diet 8 was whole-egg powder. On the 8th day of experiment 5 animals per group were labelled by intragastric infusion with 14 C-glutamic acid. During the following 24 hours the excretion of CO 2 and 14 CO 2 was measured. Throughout the experimental feeding body weight was relative constant, however, when the synthetic diets were fed it was necessary to increase the daily amount of energy from 460 to 480 kJ/kg/sup 0.67/. The relative 14 CO 2 excretion within 24 hours was 68-75 % of the dose. However, the main part of the amount of radioactivity excreted during 24 hours was already found after 4 to 6 hours. Exponential functions calculated from the data of cumulative 14 CO 2 excretion suggest the existence of a fast process of 14 CO 2 formation directly from 14 C-glutamic acid, reaching a plateau within 2 hours and a slow process of oxidation of intermediates of glutamic acid metabolism, causing a continued 14 CO 2 formation even after 24 hours. The oxidation of 14 C-glutamic acid to CO 2 decreased 2 to 14 hours after labelling if the glutamic acid content of the diet increased. The same was found for the specific radioactivity of 14 CO 2 . A storage of intermediates of glutamic acid before degradation was assumed. (author)

  11. Immunochemical characterization of the brain glutamate binding protein

    International Nuclear Information System (INIS)

    Roy, S.

    1986-01-01

    A glutamate binding protein (GBP) was purified from bovine and rat brain to near homogeneity. Polyclonal antibodies were raised against this protein. An enzyme-linked-immunosorbent-assay was used to quantify and determine the specificity of the antibody response. The antibodies were shown to strongly react with bovine brain GBP and the analogous protein from rat brain. The antibodies did not show any crossreactivity with the glutamate metabolizing enzymes, glutamate dehydrogenase, glutamine synthetase and glutamyl transpeptidase, however it crossreacted moderately with glutamate decarboxylase. The antibodies were also used to define the possible physiologic activity of GBP in synaptic membranes. The antibodies were shown: (i) to inhibit the excitatory amino-acid stimulation of thiocyanate (SCN)flux, (ii) had no effect on transport of L-Glutamic acid across the synaptic membrane, and (iii) had no effect on the depolarization-induced release of L-glutamate. When the anti-GBP antibodies were used to localize and quantify the GBP distribution in various subcellular fractions and in brain tissue samples, it was found that the hippocampus had the highest immunoreactivity followed by the cerebral cortex, cerebellar cortex and caudate-putamen. The distribution of immunoreactivity in the subcellular fraction were as follows: synaptic membranes > crude mitochondrial fraction > homogenate > myelin. In conclusion these studies suggest that: (a) the rat brain GBP and the bovine brain GBP are immunologically homologous protein, (b) there are no structural similarities between the GBP and the glutamate metabolizing enzymes with the exception of glutamate decarboxylase and (c) the subcellular and regional distribution of the GBP immunoreactivity followed a similar pattern as observed for L-[ 3 H]-binding

  12. Characteristics of pools used by adult summer steelhead oversummering in the New River, California

    Science.gov (United States)

    Rodney J. Nakamoto

    1994-01-01

    Abstract - I assessed characteristics of pools used by oversummering adults of summer steelhead Oncorhynchus mykiss between July and October 1991 in the New River, northwestern California. Most fish occupied channel confluence pools and other pools of moderate size (200-1,200 m 2); these pools had less than 35% substrate embeddedness and mean water depths of about 1.0...

  13. Synaptically evoked glutamate transporter currents in Spinal Dorsal Horn Astrocytes

    Directory of Open Access Journals (Sweden)

    Dougherty Patrick M

    2009-07-01

    Full Text Available Abstract Background Removing and sequestering synaptically released glutamate from the extracellular space is carried out by specific plasma membrane transporters that are primarily located in astrocytes. Glial glutamate transporter function can be monitored by recording the currents that are produced by co-transportation of Na+ ions with the uptake of glutamate. The goal of this study was to characterize glutamate transporter function in astrocytes of the spinal cord dorsal horn in real time by recording synaptically evoked glutamate transporter currents. Results Whole-cell patch clamp recordings were obtained from astrocytes in the spinal substantia gelatinosa (SG area in spinal slices of young adult rats. Glutamate transporter currents were evoked in these cells by electrical stimulation at the spinal dorsal root entry zone in the presence of bicuculline, strychnine, DNQX and D-AP5. Transporter currents were abolished when synaptic transmission was blocked by TTX or Cd2+. Pharmacological studies identified two subtypes of glutamate transporters in spinal astrocytes, GLAST and GLT-1. Glutamate transporter currents were graded with stimulus intensity, reaching peak responses at 4 to 5 times activation threshold, but were reduced following low-frequency (0.1 – 1 Hz repetitive stimulation. Conclusion These results suggest that glutamate transporters of spinal astrocytes could be activated by synaptic activation, and recording glutamate transporter currents may provide a means of examining the real time physiological responses of glial cells in spinal sensory processing, sensitization, hyperalgesia and chronic pain.

  14. Influence of glutamic acid enantiomers on C-mineralization.

    Science.gov (United States)

    Formánek, Pavel; Vranová, Valerie; Lojková, Lea

    2015-02-01

    Seasonal dynamics in the mineralization of glutamic acid enantiomers in soils from selected ecosystems was determined and subjected to a range of treatments: ambient x elevated CO2 level and meadow x dense x thinned forest environment. Mineralization of glutamic acid was determined by incubation of the soil with 2 mg L- or D-glutamic acid g(-1) of dry soil to induce the maximum respiration rate. Mineralization of glutamic acid enantiomers in soils fluctuates over the course of a vegetation season, following a similar trend across a range of ecosystems. Mineralization is affected by environmental changes and management practices, including elevated CO2 level and thinning intensity. L-glutamic acid metabolism is more dependent on soil type as compared to metabolism of its D-enantiomer. The results support the hypothesis that the slower rate of D- compared to L- amino acid mineralization is due to different roles in anabolism and catabolism of the soil microbial community. © 2014 Wiley Periodicals, Inc.

  15. Glutamine and glutamate: Nonessential or essential amino acids?

    Directory of Open Access Journals (Sweden)

    Malcolm Watford

    2015-09-01

    Full Text Available Glutamine and glutamate are not considered essential amino acids but they play important roles in maintaining growth and health in both neonates and adults. Although glutamine and glutamate are highly abundant in most feedstuffs there is increasing evidence that they may be limiting during pregnancy, lactation and neonatal growth, particularly when relatively low protein diets are fed. Supplementation of diets with glutamine, glutamate or both at 0.5 to 1.0% to both suckling and recently weaned piglets improves intestinal and immune function and results in better growth. In addition such supplementation to the sow prevents some of the loss of lean body mass during lactation, and increases milk glutamine content. However, a number of important questions related to physiological condition, species under study and the form and amount of the supplements need to be addressed before the full benefits of glutamine and glutamate supplementation in domestic animal production can be realized. Keywords: Amino acid, Glutamate, Glutamine, Lactation, Pregnancy, Growth

  16. Dysfunctional TCA-Cycle Metabolism in Glutamate Dehydrogenase Deficient Astrocytes.

    Science.gov (United States)

    Nissen, Jakob D; Pajęcka, Kamilla; Stridh, Malin H; Skytt, Dorte M; Waagepetersen, Helle S

    2015-12-01

    Astrocytes take up glutamate in the synaptic area subsequent to glutamatergic transmission by the aid of high affinity glutamate transporters. Glutamate is converted to glutamine or metabolized to support intermediary metabolism and energy production. Glutamate dehydrogenase (GDH) and aspartate aminotransferase (AAT) catalyze the reversible reaction between glutamate and α-ketoglutarate, which is the initial step for glutamate to enter TCA cycle metabolism. In contrast to GDH, AAT requires a concomitant interconversion of oxaloacetate and aspartate. We have investigated the role of GDH in astrocyte glutamate and glucose metabolism employing siRNA mediated knock down (KD) of GDH in cultured astrocytes using stable and radioactive isotopes for metabolic mapping. An increased level of aspartate was observed upon exposure to [U-(13) C]glutamate in astrocytes exhibiting reduced GDH activity. (13) C Labeling of aspartate and TCA cycle intermediates confirmed that the increased amount of aspartate is associated with elevated TCA cycle flux from α-ketoglutarate to oxaloacetate, i.e. truncated TCA cycle. (13) C Glucose metabolism was elevated in GDH deficient astrocytes as observed by increased de novo synthesis of aspartate via pyruvate carboxylation. In the absence of glucose, lactate production from glutamate via malic enzyme was lower in GDH deficient astrocytes. In conclusions, our studies reveal that metabolism via GDH serves an important anaplerotic role by adding net carbon to the TCA cycle. A reduction in GDH activity seems to cause the astrocytes to up-regulate activity in pathways involved in maintaining the amount of TCA cycle intermediates such as pyruvate carboxylation as well as utilization of alternate substrates such as branched chain amino acids. © 2015 Wiley Periodicals, Inc.

  17. Combretastatin A4/poly(L-glutamic acid-graft-PEG conjugates self-assembled to nanoparticles

    Directory of Open Access Journals (Sweden)

    Yang Ou

    2018-03-01

    Full Text Available Combretastatin A4 (CA4 possesses varying ability to cause vascular disruption in tumors, while the short half-life, low water solubility and deactivation of many CA4 analogs during storage limited its antitumor efficacy and drug stability. A novel macromolecular conjugate of CA4 (CA4-PL was synthesized by covalent bonding of CA4 onto poly(L-glutamic acid-graft-polyethylene glycol (PLG-g-PEG via Yamaguchi reaction. The obtained CA4-PL was characterized by 1H NMR, GPC, and UV methods, and the properties of the nanoparticles composed of CA4-PL, including critical aggregation concentration, size and size distribution, and morphology, were investigated. CA4-PL can self-assemble to form micelle-like nanoparticles of 80~120 nm in diameter, which may have potential to improve the blood circulation period as well as the targetability of CA4, and find applications to treat various tumors when combined with traditional chemotherapy or radio therapy. Keywords: Combretastatin A4, Macromolecular conjugate, Poly(L-glutamic acid-graft-polyethylene glycol, Self-assemble, Nanoparticles

  18. Livestock Grazing as a Driver of Vernal Pool Ecohydrology

    Science.gov (United States)

    Michaels, J.; McCarten, N. F.

    2017-12-01

    Vernal pools are seasonal wetlands that host rare plant communities of high conservation priority. Plant community composition is largely driven by pool hydroperiod. A previous study found that vernal pools grazed by livestock had longer hydroperiods compared with pools excluded from grazing for 10 years, and suggests that livestock grazing can be used to protect plant diversity. It is important to assess whether observed differences are due to the grazing or due to water balance variables including upland discharge into or out of the pools since no a priori measurements were made of the hydrology prior to grazing. To address this question, in 2016 we compared 15 pools that have been grazed continuously and 15 pools that have been fenced off for over 40 years at a site in Sacramento County. We paired pools based on abiotic characteristics (size, shape, slope, soil type) to minimize natural variation. We sampled vegetation and water depth using Solinst level loggers. We found that plant diversity and average hydroperiod was significantly higher in the grazed pools. We are currently measuring groundwater connectivity and upland inputs in order to compare the relative strength of livestock grazing as a driver of hydroperiod to these other drivers.

  19. Posttranslational Modification Biology of Glutamate Receptors and Drug Addiction

    Directory of Open Access Journals (Sweden)

    Li-Min eMao

    2011-03-01

    Full Text Available Posttranslational covalent modifications of glutamate receptors remain a hot topic. Early studies have established that this family of receptors, including almost all ionotropic and metabotropic glutamate receptor subtypes, undergoes active phosphorylation at serine, threonine, or tyrosine residues on their intracellular domains. Recent evidence identifies several glutamate receptor subtypes to be direct substrates for palmitoylation at cysteine residues. Other modifications such as ubiquitination and sumoylation at lysine residues also occur to certain glutamate receptors. These modifications are dynamic and reversible in nature and are regulatable by changing synaptic inputs. The regulated modifications significantly impact the receptor in many ways, including interrelated changes in biochemistry (synthesis, subunit assembling and protein-protein interactions, subcellular redistribution (trafficking, endocytosis, synaptic delivery and clustering, and physiology, usually associated with changes in synaptic plasticity. Glutamate receptors are enriched in the striatum and cooperate closely with dopamine to regulate striatal signaling. Emerging evidence shows that modification processes of striatal glutamate receptors are sensitive to addictive drugs, such as psychostimulants (cocaine and amphetamines. Altered modifications are believed to be directly linked to enduring receptor/synaptic plasticity and drug-seeking. This review summarizes several major types of modifications of glutamate receptors and analyzes the role of these modifications in striatal signaling and in the pathogenesis of psychostimulant addiction.

  20. Serum Glutamic-Oxaloacetic Transaminase (GOT) and Glutamic-Pyruvic Transaminase (GPT) Levels in Children and Adolescents with Intellectual Disabilities

    Science.gov (United States)

    Lin, Jin-Ding; Lin, Pei-Ying; Chen, Li-Mei; Fang, Wen-Hui; Lin, Lan-Ping; Loh, Ching-Hui

    2010-01-01

    The elevated serum glutamic-oxaloacetic transaminase (GOT) and glutamic-pyruvic transaminase (GPT) rate among people with intellectual disabilities (ID) is unknown and have not been sufficiently studies. The present paper aims to provide the profile of GOT and GPT, and their associated relationship with other biochemical levels of children or…

  1. Co-Production of Nattokinase and Poly (γ-Glutamic Acid Under Solid-State Fermentation Using Soybean and Rice Husk

    Directory of Open Access Journals (Sweden)

    Guangjun Nie

    2015-10-01

    Full Text Available ABSTRACTThe aim of this work was to study the co-production of nattokinase and poly (γ-glutamic acid by Bacillus subtilis natto with soybean and rice husk under solid-state fermentation (SSF. The results showed that the size of soybean particle and rice husk significantly improved the co-production of nattokinase and poly (γ-glutamic acid, yielding 2503.4 IU/gs and 320 mg/gs, respectively in the improved culture medium composed of 16.7% soybean flour and 13.3% rice husk with 70% water content. The yields increased by approximate 7- and 2-fold factor relative to their original ones. Thus, the co-production of nattokinase and poly (γ-glutamic acid under SSF could be considered as an efficient method to exploit agro-residues for economical production of some higher-value products.

  2. Sparse feature learning for instrument identification: Effects of sampling and pooling methods.

    Science.gov (United States)

    Han, Yoonchang; Lee, Subin; Nam, Juhan; Lee, Kyogu

    2016-05-01

    Feature learning for music applications has recently received considerable attention from many researchers. This paper reports on the sparse feature learning algorithm for musical instrument identification, and in particular, focuses on the effects of the frame sampling techniques for dictionary learning and the pooling methods for feature aggregation. To this end, two frame sampling techniques are examined that are fixed and proportional random sampling. Furthermore, the effect of using onset frame was analyzed for both of proposed sampling methods. Regarding summarization of the feature activation, a standard deviation pooling method is used and compared with the commonly used max- and average-pooling techniques. Using more than 47 000 recordings of 24 instruments from various performers, playing styles, and dynamics, a number of tuning parameters are experimented including the analysis frame size, the dictionary size, and the type of frequency scaling as well as the different sampling and pooling methods. The results show that the combination of proportional sampling and standard deviation pooling achieve the best overall performance of 95.62% while the optimal parameter set varies among the instrument classes.

  3. Titanium distribution in swimming pool water is dominated by dissolved species

    International Nuclear Information System (INIS)

    David Holbrook, R.; Motabar, Donna; Quiñones, Oscar; Stanford, Benjamin; Vanderford, Brett; Moss, Donna

    2013-01-01

    The increased use of titanium dioxide nanoparticles (nano-TiO 2 ) in consumer products such as sunscreen has raised concerns about their possible risk to human and environmental health. In this work, we report the occurrence, size fractionation and behavior of titanium (Ti) in a children's swimming pool. Size-fractionated samples were analyzed for Ti using ICP-MS. Total titanium concentrations ([Ti]) in the pool water ranged between 21 μg/L and 60 μg/L and increased throughout the 101-day sampling period while [Ti] in tap water remained relatively constant. The majority of [Ti] was found in the dissolved phase (<1 kDa), with only a minor fraction of total [Ti] being considered either particulate or microparticulate. Simple models suggest that evaporation may account for the observed variation in [Ti], while sunscreen may be a relevant source of particulate and microparticule Ti. Compared to diet, incidental ingestion of nano-Ti from swimming pool water is minimal. -- Highlights: •Total titanium concentrations in unfiltered swimming pool water ranged between 21 and 60 μg/L. •Evaporation of the swimming pool water is suspected of causing a temporal increase in [Ti]. •The vast majority of Ti is found in the dissolved phase (<1 kD). •Swimming pools are not a significant Ti source for human exposure via ingestion. -- In children's swimming pool water, the majority of titanium is found in the dissolved phase

  4. Longevity of Wood-Forced Pools in an Old-Growth Forest

    Science.gov (United States)

    Buffington, J. M.; Woodsmith, R. D.; Johnson, A. C.

    2009-12-01

    Wood debris plays an important role in scouring pools in forest channels and providing resultant habitat for aquatic organisms. We investigated the longevity of such pools in a gravel-bed river flowing through old-growth forest in southeastern Alaska by aging trees and “bear’s bread” fungi (Ganoderma applanatum, Fomitopsis pinicola) growing on pool-forming wood debris. Ages were determined by counting annual growth rings from cores and cross sections of trees and fungi growing on the wood debris. These ages are minimum values because they do not account for lag time between debris recruitment and seedling/spore establishment on the debris, nor do they account for flood scour that may periodically reset tree and fungi growth on the debris. The study stream has a gradient of about 1%, bankfull width and depth of 13.3 and 0.78 m, respectively, median grain size of 18 mm, a high wood loading (0.8 pieces/m), and a correspondingly low pool spacing (0.3 bankfull widths/pool), with 81% of the pools forced by wood debris. The size of wood debris in the study stream is large relative to the channel (average log length of 7.6 m and diameter of 0.35 m), rendering most debris immobile. Eighty-one pool-forming pieces of wood were dated over 1.2 km of stream length, with 28% of these pieces causing scour of more than one pool. In all, 122 wood-forced pools were dated, accounting for 38% of all pools at the site and 47% of the wood-forced pools. Fifty-three percent of the wood-forced pools lacked datable wood because these pieces either: were newly recruited; had been scoured by floods; or were contained below the active channel elevation, prohibiting vegetation establishment on the wood debris (the most common cause). The debris age distribution declined exponentially from 2 to 113 yrs., with a median value of 18 yrs. Similar exponential residence time distributions have been reported in other studies, but our analysis focused specifically on the ages of pool-forming wood

  5. Just like the lottery? Player behaviour and anomalies in the market for football pools.

    Science.gov (United States)

    Forrest, David; Pérez, Levi

    2015-06-01

    Football pools were an antecedent to lotto in providing a long-odds, high-prize gambling opportunity for a mass market in Europe. Even after lotto has become well established, pools games continue to occupy a significant niche in the gaming market in several jurisdictions, most notably Spain. This paper employs 23 years of sales data from the national pools game in Spain to investigate similarities between the behaviour of lotto players and pools players. It observes similar phenomena as have been noted in lotto sales studies, including strong sensitivity of sales to the size of jackpot on offer, significant habit effects, a halo effect whereby there is some short-term persistence in increased sales whenever a high jackpot is offered (even after jackpot size has returned to normal), and a tendency to jackpot fatigue (over time, the size of the jackpot has to be increased to more than before to stimulate the same increase in sales). Notwithstanding that the football pools are marketed as based on knowledge and understanding of sport whereas lotto is a pure numbers game, modelling sales of the pools therefore yields findings very similar to those reported in the literature on lotto. This suggests that both sets of players share common psychological and cognitive traits and economic motivation. Those responsible for promoting pools should therefore be able to draw on findings from the much more extensive literature on lotto when formulating strategy in terms of game design and marketing.

  6. DNA pooling strategies for categorical (ordinal) traits

    Science.gov (United States)

    Despite reduced genotyping costs in recent years, obtaining genotypes for all individuals in a population may still not be feasible when sample size is large. DNA pooling provides a useful alternative to determining genotype effects. Clustering algorithms allow for grouping of individuals (observati...

  7. Modulation of gene expression of adenosine and metabotropic glutamate receptors in rat's neuronal cells exposed to L-glutamate and [60]fullerene.

    Science.gov (United States)

    Giust, Davide; Da Ros, Tatiana; Martín, Mairena; Albasanz, José Luis

    2014-08-01

    L-Glutamate (L-Glu) has been often associated not only to fundamental physiological roles, as learning and memory, but also to neuronal cell death and the genesis and development of important neurodegenerative diseases. Herein we studied the variation in the adenosine and metabotropic glutamate receptors expression induced by L-Glu treatment in rat's cortical neurons. The possibility to have structural alteration of the cells induced by L-Glu (100 nM, 1 and 10 microM) has been addressed, studying the modulation of microtubule associated protein-2 (MAP-2) and neurofilament heavy polypeptide (NEFH), natively associated proteins to the dendritic shape maintenance. Results showed that the proposed treatments were not destabilizing the cells, so the L-Glu concentrations were acceptable to investigate fluctuation in receptors expression, which were studied by RT-PCR. Interestingly, C60 fullerene derivative t3ss elicited a protective effect against glutamate toxicity, as demonstrated by MTT assay. In addition, t3ss compound exerted a different effect on the adenosine and metabotropic glutamate receptors analyzed. Interestingly, A(2A) and mGlu1 mRNAs were significantly decreased in conditions were t3ss neuroprotected cortical neurons from L-Glu toxicity. In summary, t3ss protects neurons from glutamate toxicity in a process that appears to be associated with the modulation of the gene expression of adenosine and metabotropic glutamate receptors.

  8. Serum Glutamate Is a Predictor for the Diagnosis of Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Gheyath Al Gawwam

    2017-01-01

    Full Text Available One neurotransmitter, glutamate, has been implicated in the autoimmune demyelination seen in multiple sclerosis (MS. Glutamate is present in many tissues in the body, so consideration should be given to whether the serum level of glutamate is likely well correlated with the activity of the disease. This research aimed to compare the serum glutamate levels from patients diagnosed with MS with those from an age-matched control population. A review of this data could shed light upon whether the serum testing of glutamate using Enzyme-Linked Immunosorbent Assay (ELISA is a reliable indicator of MS activity. Serum samples were obtained from 55 patients with different patterns of MS and from 25 healthy adults as a control group. The ELISA technique was used to determine the glutamate levels in the serum samples. The mean serum glutamate level for patients with MS was 1.318±0.543 nmol/ml and that of the controls was 0.873±0.341 nmol/ml. The serum glutamate levels showed an area under the curve via the receiver operating characteristics (ROC of 0.738, which was significant (p value = 0.001. The present study is the first to establish a strong connection between the serum glutamate levels and MS patients, where there was statistically significant elevation of serum glutamate in MS patients; hence this elevation might be used as a monitor to help in the diagnosis of MS patients.

  9. Hawaii ESI: POOLS (Anchialine Pool Points)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This data set contains sensitive biological resource data for anchialine pools in Hawaii. Anchialine pools are small, relatively shallow coastal ponds that occur...

  10. Experimental investigation of particulate debris spreading in a pool

    Energy Technology Data Exchange (ETDEWEB)

    Konovalenko, A., E-mail: kono@kth.se [Division of Nuclear Power Safety, Royal Institute of Technology (KTH) , Roslagstullsbacken 21, Stockholm 106 91 (Sweden); Basso, S., E-mail: simoneb@kth.se [Division of Nuclear Power Safety, Royal Institute of Technology (KTH) , Roslagstullsbacken 21, Stockholm 106 91 (Sweden); Kudinov, P., E-mail: pkudinov@kth.se [Division of Nuclear Power Safety, Royal Institute of Technology (KTH) , Roslagstullsbacken 21, Stockholm 106 91 (Sweden); Yakush, S.E., E-mail: yakush@ipmnet.ru [Institute for Problems in Mechanics of the Russian Academy of Sciences, Ave. Vernadskogo 101 Bldg 1, Moscow 119526 (Russian Federation)

    2016-02-15

    Termination of severe accident progression by core debris cooling in a deep pool of water under reactor vessel is considered in several designs of light water reactors. However, success of this accident mitigation strategy is contingent upon the effectiveness of heat removal by natural circulation from the debris bed. It is assumed that a porous bed will be formed in the pool in the process of core melt fragmentation and quenching. Debris bed coolability depends on its properties and system conditions. The properties of the bed, including its geometry are the outcomes of the debris bed formation process. Spreading of the debris particles in the pool by two-phase turbulent flows induced by the heat generated in the bed can affect the shape of the bed and thus influence its coolability. The goal of this work is to provide experimental data on spreading of solid particles in the pool by large-scale two-phase flow. The aim is to provide data necessary for understanding of separate effects and for development and validation of models and codes. Validated codes can be then used for prediction of debris bed formation under prototypic severe accident conditions. In PDS-P (Particulate Debris Spreading in the Pool) experiments, air injection at the bottom of the test section is employed as a means to create large-scale flow in the pool in isothermal conditions. The test section is a rectangular tank with a 2D slice geometry, it has fixed width (72 mm), adjustable length (up to 1.5 m) and allows water filling to the depth of up to 1 m. Variable pool length and depth allows studying two-phase circulating flows of different characteristic sizes and patterns. The average void fraction in the pool is determined by video recording and subsequent image processing. Particles are supplied from the top of the facility above the water surface. Results of several series of PDS-P experiments are reported in this paper. The influence of the gas flow rate, pool dimensions, particle density

  11. Cash pooling

    OpenAIRE

    Lozovaya, Karina

    2009-01-01

    This work makes a mention of cash management. At next chapter describes two most known theoretical models of cash management -- Baumol Model and Miller-Orr Model. Principal part of work is about cash pooling, types of cash pooling, cash pooling at Czech Republic and influence of cash pooling over accounting and taxes.

  12. [Determination of glutamic acid in biological material by capillary electrophoresis].

    Science.gov (United States)

    Narezhnaya, E; Krukier, I; Avrutskaya, V; Degtyareva, A; Igumnova, E A

    2015-01-01

    The conditions for the identification and determination of Glutamic acid by capillary zone electrophoresis without their preliminary derivatization have been optimized. The effect of concentration of buffer electrolyte and pH on determination of Glutamic acid has been investigated. It is shown that the 5 Mm borate buffer concentration and a pH 9.15 are optimal. Quantitative determination of glutamic acid has been carried out using a linear dependence between the concentration of the analyte and the area of the peak. The accuracy and reproducibility of the determination are confirmed by the method "introduced - found". Glutamic acid has been determined in the placenta homogenate. The duration of analysis doesn't exceed 30 minutes. The results showed a decrease in the level of glutamic acid in cases of pregnancy complicated by placental insufficiency compared with the physiological, and this fact allows to consider the level of glutamic acid as a possible marker of complicated pregnancy.

  13. Glucose, Lactate, β-Hydroxybutyrate, Acetate, GABA, and Succinate as Substrates for Synthesis of Glutamate and GABA in the Glutamine-Glutamate/GABA Cycle.

    Science.gov (United States)

    Hertz, Leif; Rothman, Douglas L

    2016-01-01

    The glutamine-glutamate/GABA cycle is an astrocytic-neuronal pathway transferring precursors for transmitter glutamate and GABA from astrocytes to neurons. In addition, the cycle carries released transmitter back to astrocytes, where a minor fraction (~25 %) is degraded (requiring a similar amount of resynthesis) and the remainder returned to the neurons for reuse. The flux in the cycle is intense, amounting to the same value as neuronal glucose utilization rate or 75-80 % of total cortical glucose consumption. This glucose:glutamate ratio is reduced when high amounts of β-hydroxybutyrate are present, but β-hydroxybutyrate can at most replace 60 % of glucose during awake brain function. The cycle is initiated by α-ketoglutarate production in astrocytes and its conversion via glutamate to glutamine which is released. A crucial reaction in the cycle is metabolism of glutamine after its accumulation in neurons. In glutamatergic neurons all generated glutamate enters the mitochondria and its exit to the cytosol occurs in a process resembling the malate-aspartate shuttle and therefore requiring concomitant pyruvate metabolism. In GABAergic neurons one half enters the mitochondria, whereas the other one half is released directly from the cytosol. A revised concept is proposed for the synthesis and metabolism of vesicular and nonvesicular GABA. It includes the well-established neuronal GABA reuptake, its metabolism, and use for resynthesis of vesicular GABA. In contrast, mitochondrial glutamate is by transamination to α-ketoglutarate and subsequent retransamination to releasable glutamate essential for the transaminations occurring during metabolism of accumulated GABA and subsequent resynthesis of vesicular GABA.

  14. Food Application of Newly Developed Handy-type Glutamate Sensor.

    Science.gov (United States)

    Mukai, Yuuka; Oikawa, Tsutomu

    2016-01-01

    Tests on physiological functions of umami have been actively conducted and a need recognized for a high-performance quantification device that is simple and cost-effective, and whose use is not limited to a particular location or user. To address this need, Ajinomoto Co. and Tanita Corp. have jointly been researching and developing a simple device for glutamate measurement. The device uses L-glutamate oxidase immobilized on a hydrogen peroxide electrode. L-glutamate in the sample is converted to α-ketoglutaric acid, which produces hydrogen peroxide. Subsequently, the electrical current from the electrochemical reaction of hydrogen peroxide is measured to determine the L-glutamate concentration. In order to evaluate its basic performance, we used this device to measure the concentration of L-glutamate standard solutions. In a concentration range of 0-1.0%, the difference from the theoretical value was minimal. The coefficient of variation (CV) value of 3 measurements was 4% or less. This shows that the device has a reasonable level of precision and accuracy. The device was also used in trial measurements of L-glutamate concentrations in food. There was a good correlation between the results obtained using the developed device and those obtained with an amino acid analyzer; the correlation coefficient was R=0.997 (n=24). In this review, we demonstrate the use of our device to measure the glutamate concentration in miso soup served daily at a home for elderly people, and other foods and ingredients.

  15. Feedback-induced glutamate spillover enhances negative feedback from horizontal cells to cones

    NARCIS (Netherlands)

    Vroman, Rozan; Kamermans, Maarten

    2015-01-01

    In the retina, horizontal cells feed back negatively to cone photoreceptors. Glutamate released from cones can spill over to neighbouring cones. Here we show that cone glutamate release induced by negative feedback can also spill over to neighbouring cones. This glutamate activates the glutamate

  16. Glutamate receptor ligands

    DEFF Research Database (Denmark)

    Guldbrandt, Mette; Johansen, Tommy N; Frydenvang, Karla Andrea

    2002-01-01

    Homologation and substitution on the carbon backbone of (S)-glutamic acid [(S)-Glu, 1], as well as absolute stereochemistry, are structural parameters of key importance for the pharmacological profile of (S)-Glu receptor ligands. We describe a series of methyl-substituted 2-aminoadipic acid (AA...

  17. Ephemeroptera, Plecoptera, and Trichoptera on Isle Royale National Park, USA, compared to mainland species pool and size distribution.

    Science.gov (United States)

    DeWalt, R Edward; South, Eric J

    2015-01-01

    Extensive sampling for aquatic insects was conducted in the orders Ephemeroptera (mayflies), Plecoptera (stoneflies), and Trichoptera (caddisflies) (EPT) of Isle Royale National Park (ISRO), Michigan, United States of America, during summer 2013. The island was ice covered until 8,000 to 10,000 years ago and is isolated by 22-70 km distance from the mainland. Two hypotheses were examined: that ISRO EPT richness would be much reduced from the mainland, and that the species colonizing ISRO would be of smaller size than mainland, adults presumably using updrafts to bridge the distance from mainland sources. Data sets were developed for known mainland EPT species and size for those species. The first hypothesis was confirmed with the mainland species pool consisting of 417 EPT, while ISRO is known to support 73 species. Richness of EPT is directly related to the number of specimens examined. Small streams supported five EPT species, while 15-25 species were found in larger streams. Lakeshores had intermediate diversity. The second hypothesis was substantiated for stoneflies, but not for mayflies or caddisflies. Stoneflies apparently are poorer fliers than either of the other two orders.

  18. 40 CFR 721.3821 - L-Glutamic acid, N-(1-oxododecyl)-.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false L-Glutamic acid, N-(1-oxododecyl... Substances § 721.3821 L-Glutamic acid, N-(1-oxododecyl)-. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as L-Glutamic acid, N-(1-oxododecyl)- (PMN P...

  19. Essential roles of aspartate aminotransferase 1 and vesicular glutamate transporters in β-cell glutamate signaling for incretin-induced insulin secretion.

    Directory of Open Access Journals (Sweden)

    Naoya Murao

    Full Text Available Incretins (GLP-1 and GIP potentiate insulin secretion through cAMP signaling in pancreatic β-cells in a glucose-dependent manner. We recently proposed a mechanistic model of incretin-induced insulin secretion (IIIS that requires two critical processes: 1 generation of cytosolic glutamate through the malate-aspartate (MA shuttle in glucose metabolism and 2 glutamate transport into insulin granules by cAMP signaling to promote insulin granule exocytosis. To directly prove the model, we have established and characterized CRISPR/Cas9-engineered clonal mouse β-cell lines deficient for the genes critical in these two processes: aspartate aminotransferase 1 (AST1, gene symbol Got1, a key enzyme in the MA shuttle, which generates cytosolic glutamate, and the vesicular glutamate transporters (VGLUT1, VGLUT2, and VGLUT3, gene symbol Slc17a7, Slc17a6, and Slc17a8, respectively, which participate in glutamate transport into secretory vesicles. Got1 knockout (KO β-cell lines were defective in cytosolic glutamate production from glucose and showed impaired IIIS. Unexpectedly, different from the previous finding that global Slc17a7 KO mice exhibited impaired IIIS from pancreatic islets, β-cell specific Slc17a7 KO mice showed no significant impairment in IIIS, as assessed by pancreas perfusion experiment. Single Slc17a7 KO β-cell lines also retained IIIS, probably due to compensatory upregulation of Slc17a6. Interestingly, triple KO of Slc17a7, Slc17a6, and Slc17a8 diminished IIIS, which was rescued by exogenously introduced wild-type Slc17a7 or Slc17a6 genes. The present study provides direct evidence for the essential roles of AST1 and VGLUTs in β-cell glutamate signaling for IIIS and also shows the usefulness of the CRISPR/Cas9 system for studying β-cells by simultaneous disruption of multiple genes.

  20. Monosodium Glutamate Toxicity

    African Journals Online (AJOL)

    Dr Olaleye

    The brain is reportedly sensitive to monosodium glutamate (MSG) toxicity via oxidative stress. Sida acuta leaf ethanolic .... wherein the right hemisphere, was preserved for histology and fixed in 10% ... Biochemical Assays: The left hemisphere of the brain samples was ...... development in male and female rats. Exp Physiol.

  1. Expression of the human isoform of glutamate dehydrogenase, hGDH2, augments TCA cycle capacity and oxidative metabolism of glutamate during glucose deprivation in astrocytes

    DEFF Research Database (Denmark)

    Nissen, Jakob D; Lykke, Kasper; Bryk, Jaroslaw

    2017-01-01

    A key enzyme in brain glutamate homeostasis is glutamate dehydrogenase (GDH) which links carbohydrate and amino acid metabolism mediating glutamate degradation to CO2 and expanding tricarboxylic acid (TCA) cycle capacity with intermediates, i.e. anaplerosis. Humans express two GDH isoforms, GDH1...... and 2, whereas most other mammals express only GDH1. hGDH1 is widely expressed in human brain while hGDH2 is confined to astrocytes. The two isoforms display different enzymatic properties and the nature of these supports that hGDH2 expression in astrocytes potentially increases glutamate oxidation...

  2. Combined glutamate and glutamine levels in pain-processing brain regions are associated with individual pain sensitivity.

    Science.gov (United States)

    Zunhammer, Matthias; Schweizer, Lauren M; Witte, Vanessa; Harris, Richard E; Bingel, Ulrike; Schmidt-Wilcke, Tobias

    2016-10-01

    The relationship between glutamate and γ-aminobutyric acid (GABA) levels in the living human brain and pain sensitivity is unknown. Combined glutamine/glutamate (Glx), as well as GABA levels can be measured in vivo with single-voxel proton magnetic resonance spectroscopy. In this cross-sectional study, we aimed at determining whether Glx and/or GABA levels in pain-related brain regions are associated with individual differences in pain sensitivity. Experimental heat, cold, and mechanical pain thresholds were obtained from 39 healthy, drug-free individuals (25 men) according to the quantitative sensory testing protocol and summarized into 1 composite measure of pain sensitivity. The Glx levels were measured using point-resolved spectroscopy at 3 T, within a network of pain-associated brain regions comprising the insula, the anterior cingulate cortex, the mid-cingulate cortex, the dorsolateral prefrontal cortex, and the thalamus. GABA levels were measured using GABA-edited spectroscopy (Mescher-Garwood point-resolved spectroscopy) within the insula, the anterior cingulate cortex, and the mid-cingulate cortex. Glx and/or GABA levels correlated positively across all brain regions. Gender, weekly alcohol consumption, and depressive symptoms were significantly associated with Glx and/or GABA levels. A linear regression analysis including all these factors indicated that Glx levels pooled across pain-related brain regions were positively associated with pain sensitivity, whereas no appreciable relationship with GABA was found. In sum, we show that the levels of the excitatory neurotransmitter glutamate and its precursor glutamine across pain-related brain regions are positively correlated with individual pain sensitivity. Future studies will have to determine whether our findings also apply to clinical populations.

  3. The Glutamine Transporters and Their Role in the Glutamate/GABA-Glutamine Cycle

    DEFF Research Database (Denmark)

    Leke, Renata; Schousboe, Arne

    2016-01-01

    in this neural communication, i.e., the transporters responsible for glutamine efflux from astrocytes and influx into the neurons, such as the members of the SNAT, LAT, y(+)LAT, and ASC families of transporters. The SNAT family consists of the transporter isoforms SNAT3 and SNAT5 that are related to efflux from......Glutamine is a key amino acid in the CNS, playing an important role in the glutamate/GABA-glutamine cycle (GGC). In the GGC, glutamine is transferred from astrocytes to neurons, where it will replenish the inhibitory and excitatory neurotransmitter pools. Different transporters participate...... the astrocytic compartment, and SNAT1 and SNAT2 that are associated with glutamine uptake into the neuronal compartment. The isoforms SNAT7 and SNAT8 do not have their role completely understood, but they likely also participate in the GGC. The isoforms LAT2 and y(+)LAT2 facilitate the exchange of neutral amino...

  4. A Glutamic Acid-Producing Lactic Acid Bacteria Isolated from Malaysian Fermented Foods

    Science.gov (United States)

    Zareian, Mohsen; Ebrahimpour, Afshin; Bakar, Fatimah Abu; Mohamed, Abdul Karim Sabo; Forghani, Bita; Ab-Kadir, Mohd Safuan B.; Saari, Nazamid

    2012-01-01

    l-glutamaic acid is the principal excitatory neurotransmitter in the brain and an important intermediate in metabolism. In the present study, lactic acid bacteria (218) were isolated from six different fermented foods as potent sources of glutamic acid producers. The presumptive bacteria were tested for their ability to synthesize glutamic acid. Out of the 35 strains showing this capability, strain MNZ was determined as the highest glutamic-acid producer. Identification tests including 16S rRNA gene sequencing and sugar assimilation ability identified the strain MNZ as Lactobacillus plantarum. The characteristics of this microorganism related to its glutamic acid-producing ability, growth rate, glucose consumption and pH profile were studied. Results revealed that glutamic acid was formed inside the cell and excreted into the extracellular medium. Glutamic acid production was found to be growth-associated and glucose significantly enhanced glutamic acid production (1.032 mmol/L) compared to other carbon sources. A concentration of 0.7% ammonium nitrate as a nitrogen source effectively enhanced glutamic acid production. To the best of our knowledge this is the first report of glutamic acid production by lactic acid bacteria. The results of this study can be further applied for developing functional foods enriched in glutamic acid and subsequently γ-amino butyric acid (GABA) as a bioactive compound. PMID:22754309

  5. Inactivation of glutamate racemase (MurI) eliminates virulence in Streptococcus mutans.

    Science.gov (United States)

    Zhang, Jianying; Liu, Jia; Ling, Junqi; Tong, Zhongchun; Fu, Yun; Liang, Min

    2016-01-01

    Inhibition of enzymes required for bacterial cell wall synthesis is often lethal or leads to virulence defects. Glutamate racemase (MurI), an essential enzyme in peptidoglycan biosynthesis, has been an attractive target for therapeutic interventions. Streptococcus mutans, one of the many etiological factors of dental caries, possesses a series of virulence factors associated with cariogenicity. However, little is known regarding the mechanism by which MurI influences pathogenesis of S. mutans. In this work, a stable mutant of S. mutans deficient in glutamate racemase (S. mutans FW1718) was constructed to investigate the impact of murI inactivation on cariogenic virulence in S. mutans UA159. Microscopy revealed that the murI mutant exhibited an enlarged cell size, longer cell chains, diminished cell⬜cell aggregation, and altered cell surface ultrastructure compared with the wild-type. Characterization of this mutant revealed that murI deficiency weakened acidogenicity, aciduricity, and biofilm formation ability of S. mutans (Pmutans virulence properties, making MurI a potential target for controlling dental caries. Copyright © 2016 Elsevier GmbH. All rights reserved.

  6. Glutamic acid and its derivatives: candidates for rational design of anticancer drugs.

    Science.gov (United States)

    Ali, Imran; Wani, Waseem A; Haque, Ashanul; Saleem, Kishwar

    2013-05-01

    Throughout the history of human civilizations, cancer has been a major health problem. Its treatment has been interesting but challenging to scientists. Glutamic acid and its derivative glutamine are known to play interesting roles in cancer genesis, hence, it was realized that structurally variant glutamic acid derivatives may be designed and developed and, might be having antagonistic effects on cancer. The present article describes the state-of-art of glutamic acid and its derivatives as anticancer agents. Attempts have been made to explore the effectivity of drug-delivery systems based on glutamic acid for the delivery of anticancer drugs. Moreover, efforts have also been made to discuss the mechanism of action of glutamic acid derivatives as anticancer agents, clinical applications of glutamic acid derivatives, as well as recent developments and future perspectives of glutamic acid drug development have also been discussed.

  7. Expression of the human isoform of glutamate dehydrogenase, hGDH2, augments TCA cycle capacity and oxidative metabolism of glutamate during glucose deprivation in astrocytes.

    Science.gov (United States)

    Nissen, Jakob D; Lykke, Kasper; Bryk, Jaroslaw; Stridh, Malin H; Zaganas, Ioannis; Skytt, Dorte M; Schousboe, Arne; Bak, Lasse K; Enard, Wolfgang; Pääbo, Svante; Waagepetersen, Helle S

    2017-03-01

    A key enzyme in brain glutamate homeostasis is glutamate dehydrogenase (GDH) which links carbohydrate and amino acid metabolism mediating glutamate degradation to CO 2 and expanding tricarboxylic acid (TCA) cycle capacity with intermediates, i.e. anaplerosis. Humans express two GDH isoforms, GDH1 and 2, whereas most other mammals express only GDH1. hGDH1 is widely expressed in human brain while hGDH2 is confined to astrocytes. The two isoforms display different enzymatic properties and the nature of these supports that hGDH2 expression in astrocytes potentially increases glutamate oxidation and supports the TCA cycle during energy-demanding processes such as high intensity glutamatergic signaling. However, little is known about how expression of hGDH2 affects the handling of glutamate and TCA cycle metabolism in astrocytes. Therefore, we cultured astrocytes from cerebral cortical tissue of hGDH2-expressing transgenic mice. We measured glutamate uptake and metabolism using [ 3 H]glutamate, while the effect on metabolic pathways of glutamate and glucose was evaluated by use of 13 C and 14 C substrates and analysis by mass spectrometry and determination of radioactively labeled metabolites including CO 2 , respectively. We conclude that hGDH2 expression increases capacity for uptake and oxidative metabolism of glutamate, particularly during increased workload and aglycemia. Additionally, hGDH2 expression increased utilization of branched-chain amino acids (BCAA) during aglycemia and caused a general decrease in oxidative glucose metabolism. We speculate, that expression of hGDH2 allows astrocytes to spare glucose and utilize BCAAs during substrate shortages. These findings support the proposed role of hGDH2 in astrocytes as an important fail-safe during situations of intense glutamatergic activity. GLIA 2017;65:474-488. © 2016 Wiley Periodicals, Inc.

  8. Complex formation between glutamic acid and molybdenum (VI)

    International Nuclear Information System (INIS)

    Gharib, Farrokh; Khorrami, S.A.; Sharifi, Sasan

    1997-01-01

    Equilibria of the reaction of molybdenum (VI) with L-glutamic acid have been studied in aqueous solution in the pH range 2.5 to 9.5, using spectrophotometric and optical rotation methods at constant ionic strength (0.15 mol dm -3 sodium perchlorate) and temperature 25 ± 0.1 degC. Our studies have shown that glutamic acid forms a mononuclear complex with Mo(VI) of the type MoO 3 L 2- at pH 5.5. The stability constant of this complexation and the dissociation constants of L-glutamic acid have been determined. (author). 17 refs., 2 figs., 4 tabs

  9. Glutamate-induced glutamate release: A proposed mechanism for calcium bursting in astrocytes

    Science.gov (United States)

    Larter, Raima; Craig, Melissa Glendening

    2005-12-01

    Here we present a new model for the generation of complex calcium-bursting patterns in astrocytes, a type of brain cell recently implicated in a variety of neural functions including memory formation. The model involves two positive feedback processes, in which the key feedback species are calcium ion and glutamate. The latter is the most abundant excitatory neurotransmitter in the brain and has been shown to be involved in bidirectional communication between astrocytes and nearby neurons. The glutamate feedback process considered here is shown to be critical for the generation of complex bursting oscillations in the astrocytes and to, perhaps, code for information which may be passed from neuron to neuron via the astrocyte. These processes may be involved in memory storage and formation as well as in mechanisms which lead to dynamical diseases such as epilepsy.

  10. The glutamate aspartate transporter (GLAST) mediates L-glutamate-stimulated ascorbate-release via swelling-activated anion channels in cultured neonatal rodent astrocytes.

    Science.gov (United States)

    Lane, Darius J R; Lawen, Alfons

    2013-03-01

    Vitamin C (ascorbate) plays important neuroprotective and neuromodulatory roles in the mammalian brain. Astrocytes are crucially involved in brain ascorbate homeostasis and may assist in regenerating extracellular ascorbate from its oxidised forms. Ascorbate accumulated by astrocytes can be released rapidly by a process that is stimulated by the excitatory amino acid, L-glutamate. This process is thought to be neuroprotective against excitotoxicity. Although of potential clinical interest, the mechanism of this stimulated ascorbate-release remains unknown. Here, we report that primary cultures of mouse and rat astrocytes release ascorbate following initial uptake of dehydroascorbate and accumulation of intracellular ascorbate. Ascorbate-release was not due to cellular lysis, as assessed by cellular release of the cytosolic enzyme lactate dehydrogenase, and was stimulated by L-glutamate and L-aspartate, but not the non-excitatory amino acid L-glutamine. This stimulation was due to glutamate-induced cellular swelling, as it was both attenuated by hypertonic and emulated by hypotonic media. Glutamate-stimulated ascorbate-release was also sensitive to inhibitors of volume-sensitive anion channels, suggesting that the latter may provide the conduit for ascorbate efflux. Glutamate-stimulated ascorbate-release was not recapitulated by selective agonists of either ionotropic or group I metabotropic glutamate receptors, but was completely blocked by either of two compounds, TFB-TBOA and UCPH-101, which non-selectively and selectively inhibit the glial Na(+)-dependent excitatory amino acid transporter, GLAST, respectively. These results suggest that an impairment of astrocytic ascorbate-release may exacerbate neuronal dysfunction in neurodegenerative disorders and acute brain injury in which excitotoxicity and/or GLAST deregulation have been implicated.

  11. Titanium distribution in swimming pool water is dominated by dissolved species.

    Science.gov (United States)

    David Holbrook, R; Motabar, Donna; Quiñones, Oscar; Stanford, Benjamin; Vanderford, Brett; Moss, Donna

    2013-10-01

    The increased use of titanium dioxide nanoparticles (nano-TiO2) in consumer products such as sunscreen has raised concerns about their possible risk to human and environmental health. In this work, we report the occurrence, size fractionation and behavior of titanium (Ti) in a children's swimming pool. Size-fractionated samples were analyzed for Ti using ICP-MS. Total titanium concentrations ([Ti]) in the pool water ranged between 21 μg/L and 60 μg/L and increased throughout the 101-day sampling period while [Ti] in tap water remained relatively constant. The majority of [Ti] was found in the dissolved phase (microparticulate. Simple models suggest that evaporation may account for the observed variation in [Ti], while sunscreen may be a relevant source of particulate and microparticule Ti. Compared to diet, incidental ingestion of nano-Ti from swimming pool water is minimal. Published by Elsevier Ltd.

  12. The role of glutamine transport in metabolism in the brain cortical tissue slice

    International Nuclear Information System (INIS)

    Hare, N.; Bubb, W.A.; Rae, C.; Broeer, S.

    2001-01-01

    The widely accepted 'glutamate/glutamine cycle' holds that glutamate released as a neurotransmitter in the brain is taken up by surrounding astrocytes, converted to neuro-inactive glutamine and transported back to neurons for reconversion to glutamate. Little, however, is known about the role of glutamine transport in this process. The situation is complicated by the fact that glutamine is transported by a variety of general amino-acid transporters of low specificity. The role of these transporters in flux of glutamine through the glutamate/glutamine cycle was investigated by 13 C NMR monitoring of the flux of C from [3- 13 C]L-lactate in guinea pig cortical tissue slices in the presence of competitive inhibitors of the A-type(α-(methylamino)isobutyrate; MeAIB) and N-type (histidine) transporters. The presence of each inhibitor (10 mM) produced no significant decrease in total metabolite pool size but resulted in a significant decrease in flux of [ 13 C] into the neurotransmitters glutamate and GABA and also into glutamine and alanine. The factional enrichment of glutamate and GABA was also significantly lower. By contrast there was no effect on the amount of [ 13 C] incorporated into aspartate isotopomers which may represent a predominantly astrocyte-labelled pool. These results are consistent with involvement of glutamine transporters in the recycling of synaptic glutamate by demonstrating partial blockage of incorporation of [ 13 C] label into neuronal metabolites

  13. Mathematical modeling of the energy consumption of heated swimming pools

    Energy Technology Data Exchange (ETDEWEB)

    Le Bel, C.; Millette, J. [LTE Shawinigan, Shawinigan, PQ (Canada)

    2007-07-01

    A mathematical model was developed to estimate the water temperature of a residential swimming pool. The model can compare 2 different situations and, if local climatic conditions are known, it can accurately predict energy costs of the pool relative to the total energy consumption of the house. When used with the appropriate energy transfer coefficient and weather file, the model can estimate the water temperature of a residential swimming pool having specific characteristics, such as in-ground, above-ground, heated or non-heated. The model is suitable for determining residential loads. It can be applied to different pool types and sizes, for different water heating scenarios and different climatic regions. Data obtained from the monitoring of water temperature and electricity use of 57 residential swimming pools was used to validate the model. In addition, 5 above-ground pools were installed on the property of LTE Shawinigan to allow for a more detailed study of the parameters involved in the thermal balance of a pool. The mathematical model, based on a global heat transfer coefficient, can determine the effect of a solar blanket and the effect of water volume. 14 refs., 5 tabs., 11 figs.

  14. Reserve growth in oil pools of Alberta : model and forecast

    Energy Technology Data Exchange (ETDEWEB)

    Verma, M.; Cook, T. [United States Geological Survey, Denver, CO (United States). Central Region

    2010-09-15

    This paper presented a reserve growth study that was conducted on oil pools in Alberta, Canada. Historical oil reserve data were evaluated to assess the potential for future reserve growth in both pools and fields, and reserve growth models and functions were developed to better forecast hydrocarbon volumes. The study also considered the sensitivity of reserve growth to such factors as pool size, porosity, and oil gravity. From 1960 to 2005, the reported known recoverable oil in Alberta, excluding the Athabasca oil sands and including only pools with adequate data, increased from 4.2 to 13.9 billion barrels of oil (BBO). New discoveries contributed 3.7 BBO and reserve growth added 6 BBO. Most reserve growth occurred in pools with more than 125,000 barrels of oil. Light-oil pools account for most of the total known oil volume and consequently showed the lowest growth. Pools with greater than 30 percent porosity grew more than pools with lower porosity reservoirs. Oil field growth was found to be almost twice that of pool growth, possibly because the analysis evaluated fields with two or more pools discovered in different years. The growth in oil volumes in Alberta pools is projected to be about 454 million barrels of oil in the period from 2006 to 2010. Over a 25-year period, the cumulative reserve growth in Alberta oil pools was substantially lower than other major petroleum-producing regions, but the growth at the field level compares well. 8 refs., 2 tabs., 9 figs.

  15. GABA and glutamate uptake and metabolism in retinal glial (Müller cells

    Directory of Open Access Journals (Sweden)

    Andreas eBringmann

    2013-04-01

    Full Text Available Müller cells, the principal glial cells of the retina, support the synaptic activity by the uptake and metabolization of extracellular neurotransmitters. Müller cells express uptake and exchange systems for various neurotransmitters including glutamate and -aminobutyric acid (GABA. Müller cells remove the bulk of extracellular glutamate in the inner retina and contribute to the glutamate clearance around photoreceptor terminals. By the uptake of glutamate, Müller cells are involved in the shaping and termination of the synaptic activity, particularly in the inner retina. Reactive Müller cells are neuroprotective, e.g., by the clearance of excess extracellular glutamate, but may also contribute to neuronal degeneration by a malfunctioning or even reversal of glial glutamate transporters, or by a downregulation of the key enzyme, glutamine synthetase. This review summarizes the present knowledge about the role of Müller cells in the clearance and metabolization of extracellular glutamate and GABA. Some major pathways of GABA and glutamate metabolism in Müller cells are described; these pathways are involved in the glutamate-glutamine cycle of the retina, in the defense against oxidative stress via the production of glutathione, and in the production of substrates for the neuronal energy metabolism.

  16. pH-jump induced α-helix folding of poly-L-glutamic acid

    International Nuclear Information System (INIS)

    Donten, Mateusz L.; Hamm, Peter

    2013-01-01

    Highlights: ► pH-jump as truly biomimetic tool to initiate non-equilibrium dynamics of biomolecules. ► Design criteria to widen the applicability of pH-jumps are developed. ► Folding of poly-L-Glu in dependence of starting pH, pH jump size and helix length. ► Length dependence provides strong evidence for a nucleation–propagation scenario. - Abstract: pH jumps are a truly biomimetic technique to initiate non-equilibrium dynamics of biomolecules. In this work, the pH jump induced α-helix folding of poly-L-glutamic acid is investigated upon proton release from o-nitrobenzaldehyde. The aim of this work is twofold: On the one hand, design criteria of pH jump experiments are discussed, on the other hand, the folding mechanism of poly-L-glutamic acid is clarified by probing the IR response of the amide I band. Its folding kinetics is studied in dependence of the starting pD, the size of the pD jump and the length of the helix. While no dependence on the first two parameters could be detected, the folding time varies from 0.6 μs to 1.8 μs for helix lengths of 20 residue to 440 residue, respectively. It converges to a long-length limit at about 50 residue, a result which is attributed to a nucleation–propagation mechanism

  17. Intramuscular temperature modulates glutamate-evoked masseter muscle pain intensity in humans.

    Science.gov (United States)

    Sato, Hitoshi; Castrillon, Eduardo E; Cairns, Brian E; Bendixen, Karina H; Wang, Kelun; Nakagawa, Taneaki; Wajima, Koichi; Svensson, Peter

    2015-01-01

    To determine whether glutamate-evoked jaw muscle pain is altered by the temperature of the solution injected. Sixteen healthy volunteers participated and received injections of hot (48°C), neutral (36°C), or cold (3°C) solutions (0.5 mL) of glutamate or isotonic saline into the masseter muscle. Pain intensity was assessed with an electronic visual analog scale (eVAS). Numeric rating scale (NRS) scores of unpleasantness and temperature perception, pain-drawing areas, and pressure pain thresholds (PPTs) were also measured. Participants filled out the McGill Pain Questionnaire (MPQ). Two-way or three-way repeated measures ANOVA were used for data analyses. Injection of hot glutamate and cold glutamate solutions significantly increased and decreased, respectively, the peak pain intensity compared with injection of neutral glutamate solution. The duration of glutamate-evoked pain was significantly longer when hot glutamate was injected than when cold glutamate was injected. No significant effect of temperature on pain intensity was observed when isotonic saline was injected. No effect of solution temperature was detected on unpleasantness, heat perception, cold perception, area of pain drawings, or PPTs. There was a significantly greater use of the "numb" term in the MPQ to describe the injection of cold solutions compared to the injection of both neutral and hot solutions. Glutamate-evoked jaw muscle pain was significantly altered by the temperature of the injection solution. Although temperature perception in the jaw muscle is poor, pain intensity is increased when the muscle tissue temperature is elevated.

  18. High-level exogenous glutamic acid-independent production of poly-(γ-glutamic acid) with organic acid addition in a new isolated Bacillus subtilis C10.

    Science.gov (United States)

    Zhang, Huili; Zhu, Jianzhong; Zhu, Xiangcheng; Cai, Jin; Zhang, Anyi; Hong, Yizhi; Huang, Jin; Huang, Lei; Xu, Zhinan

    2012-07-01

    A new exogenous glutamic acid-independent γ-PGA producing strain was isolated and characterized as Bacillus subtilis C10. The factors influencing the endogenous glutamic acid supply and the biosynthesis of γ-PGA in this strain were investigated. The results indicated that citric acid and oxalic acid showed the significant capability to support the overproduction of γ-PGA. This stimulated increase of γ-PGA biosynthesis by citric acid or oxalic acid was further proved in the 10 L fermentor. To understand the possible mechanism contributing to the improved γ-PGA production, the activities of four key intracellular enzymes were measured, and the possible carbon fluxes were proposed. The result indicated that the enhanced level of pyruvate dehydrogenase (PDH) activity caused by oxalic acid was important for glutamic acid synthesized de novo from glucose. Moreover, isocitrate dehydrogenase (ICDH) and glutamate dehydrogenase (GDH) were the positive regulators of glutamic acid biosynthesis, while 2-oxoglutarate dehydrogenase complex (ODHC) was the negative one. Copyright © 2012 Elsevier Ltd. All rights reserved.

  19. Solar swimming pool

    Energy Technology Data Exchange (ETDEWEB)

    1985-01-01

    This report examines the feasibility of using solar collectors to heat the water in a previously unheated outdoor swimming pool. The solar system is used in conjunction with a pool blanket, to conserve heat when the pool is not in use. Energy losses through evaporation can be reduced by as much as 70% by a pool blanket. A total of 130 m{sup 2} of highly durable black synthetic collectors were installed on a support structure at a 30{degree} angle from the horizontal, oriented to the south. Circulation of pool water though the collectors, which is controlled by a differential thermostat, was done with the existing pool pump. Before installation the pool temperature averaged 16{degree}C; after installation it ranged from 20{degree} to 26{degree}C. It was hard to distinguish how much pool heating was due to the solar system and how much heat was retained by the pool blanket. However, the pool season was extended by five weeks and attendance tripled. 2 figs.

  20. 21 CFR 522.1125 - Hemoglobin glutamer-200 (bovine).

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Hemoglobin glutamer-200 (bovine). 522.1125 Section... (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.1125 Hemoglobin glutamer-200 (bovine). (a) Specifications. Each 125 milliliter bag contains 13...

  1. Deletion of genes involved in glutamate metabolism to improve poly-gamma-glutamic acid production in B. amyloliquefaciens LL3.

    Science.gov (United States)

    Zhang, Wei; He, Yulian; Gao, Weixia; Feng, Jun; Cao, Mingfeng; Yang, Chao; Song, Cunjiang; Wang, Shufang

    2015-02-01

    Here, we attempted to elevate poly-gamma-glutamic acid (γ-PGA) production by modifying genes involved in glutamate metabolism in Bacillus amyloliquefaciens LL3. Products of rocR, rocG and gudB facilitate the conversion from glutamate to 2-oxoglutarate in Bacillus subtillis. The gene odhA is responsible for the synthesis of a component of the 2-oxoglutarate dehydrogenase complex that catalyzes the oxidative decarboxylation of 2-oxoglutarate to succinyl coenzyme A. In-frame deletions of these four genes were performed. In shake flask experiments the gudB/rocG double mutant presented enhanced production of γ-PGA, a 38 % increase compared with wild type. When fermented in a 5-L fermenter with pH control, the γ-PGA yield of the rocR mutant was increased to 5.83 g/L from 4.55 g/L for shake flask experiments. The gudB/rocG double mutant produced 5.68 g/L γ-PGA compared with that of 4.03 g/L for the wild type, a 40 % increase. Those results indicated the possibility of improving γ-PGA production by modifying glutamate metabolism, and identified potential genetic targets to improve γ-PGA production.

  2. Effects of aromatic amino acids on glutamate-induced neuronal cell death

    International Nuclear Information System (INIS)

    Zafar, Z.; Sumners, C.

    2005-01-01

    Glutamate accumulation is believed to lead to overstimulation of glutamate receptors which results in neuronal death. The protective effects of aromatic amino acids on glutamate induced neuronal cell death were examined using rat cerebral cortical neurons. Neuronal death is quantified by measuring lactate dehydrogenase (LDH) using a spectrophotometric microtiter plate reader (ELISA reader). Neuronal cells were incubated with varying doses of glutamate plus or minus the aromatic amino acid D-Phenylalanine (D-Phe) for different time periods to observe protection against cytotoxicity. Percent cytotoxicity was seen to follow a dose dependent rise with increasing concentrations of glutamate, reaching a plateau at around 100 -500 uM glutamate. Lower levels of cytotoxicity were achieved with cell exposed to D-Phe and Dibromo tyrosine (DBrT). 48-hour experimental runs were also carried out to further investigate the mode of action of D-Phe. It was found that the difference between cytotoxicity levels of control cells and protected cells was higher over longer time. (author)

  3. Protective Effect of Edaravone on Glutamate-Induced Neurotoxicity in Spiral Ganglion Neurons

    Directory of Open Access Journals (Sweden)

    Xiaohui Bai

    2016-01-01

    Full Text Available Glutamate is an important excitatory neurotransmitter in mammalian brains, but excessive amount of glutamate can cause “excitotoxicity” and lead to neuronal death. As bipolar neurons, spiral ganglion neurons (SGNs function as a “bridge” in transmitting auditory information from the ear to the brain and can be damaged by excessive glutamate which results in sensorineural hearing loss. In this study, edaravone, a free radical scavenger, elicited both preventative and therapeutic effects on SGNs against glutamate-induced cell damage that was tested by MTT assay and trypan blue staining. Ho.33342 and PI double staining revealed that apoptosis as well as necrosis took place during glutamate treatment, and apoptosis was the main type of cell death. Oxidative stress played an important role in glutamate-induced cell damage but pretreatment with edaravone alleviated cell death. Results of western blot demonstrated that mechanisms underlying the toxicity of glutamate and the protection of edaravone were related to the PI3K pathway and Bcl-2 protein family.

  4. Protective Effect of Edaravone on Glutamate-Induced Neurotoxicity in Spiral Ganglion Neurons

    Science.gov (United States)

    Bai, Xiaohui; Zhang, Chi; Chen, Aiping; Liu, Wenwen; Li, Jianfeng; Sun, Qian

    2016-01-01

    Glutamate is an important excitatory neurotransmitter in mammalian brains, but excessive amount of glutamate can cause “excitotoxicity” and lead to neuronal death. As bipolar neurons, spiral ganglion neurons (SGNs) function as a “bridge” in transmitting auditory information from the ear to the brain and can be damaged by excessive glutamate which results in sensorineural hearing loss. In this study, edaravone, a free radical scavenger, elicited both preventative and therapeutic effects on SGNs against glutamate-induced cell damage that was tested by MTT assay and trypan blue staining. Ho.33342 and PI double staining revealed that apoptosis as well as necrosis took place during glutamate treatment, and apoptosis was the main type of cell death. Oxidative stress played an important role in glutamate-induced cell damage but pretreatment with edaravone alleviated cell death. Results of western blot demonstrated that mechanisms underlying the toxicity of glutamate and the protection of edaravone were related to the PI3K pathway and Bcl-2 protein family. PMID:27957345

  5. Pool size ratio of the substantia nigra in Parkinson's disease derived from two different quantitative magnetization transfer approaches

    Energy Technology Data Exchange (ETDEWEB)

    Trujillo, Paula [Department of Neuroradiology, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Milan, MI (Italy); Vanderbilt University Medical Center, Department of Neurology, Nashville, TN (United States); Summers, Paul E.; Costa, Antonella [Department of Neuroradiology, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Milan, MI (Italy); Smith, Alex K. [University of Oxford, Centre for Functional Magnetic Resonance Imaging of the Brain (FMRIB), Nuffield Department of Clinical Neuroscience, Oxford (United Kingdom); Smith, Seth A. [Vanderbilt University Institute of Imaging Science, Nashville, TN (United States); Vanderbilt University, Department of Biomedical Engineering, Nashville, TN (United States); Mainardi, Luca T.; Cerutti, Sergio [Department of Electronics, Information and Bioengineering, Politecnico di Milano, Milan, MI (Italy); Claassen, Daniel O. [Vanderbilt University Medical Center, Department of Neurology, Nashville, TN (United States)

    2017-12-15

    We sought to measure quantitative magnetization transfer (qMT) properties of the substantia nigra pars compacta (SNc) in patients with Parkinson's disease (PD) and healthy controls (HCs) using a full qMT analysis and determine whether a rapid single-point measurement yields equivalent results for pool size ratio (PSR). Sixteen different MT-prepared MRI scans were obtained at 3 T from 16 PD patients and eight HCs, along with B1, B0, and relaxation time maps. Maps of PSR, free and macromolecular pool transverse relaxation times (T{sub 2}{sup f}, T{sub 2}{sup m}) and rate of MT exchange between pools (k{sub mf}) were generated using a full qMT model. PSR maps were also generated using a single-point qMT model requiring just two MT-prepared images. qMT parameter values of the SNc, red nucleus, cerebral crus, and gray matter were compared between groups and methods. PSR of the SNc was the only qMT parameter to differ significantly between groups (p < 0.05). PSR measured via single-point analysis was less variable than with the full MT model, provided slightly better differentiation of PD patients from HCs (area under curve 0.77 vs. 0.75) with sensitivity of 0.75 and specificity of 0.87, and was better than transverse relaxation time in distinguishing PD patients from HCs (area under curve 0.71, sensitivity 0.87, and specificity 0.50). The increased PSR observed in the SNc of PD patients may provide a novel biomarker of PD, possibly associated with an increased macromolecular content. Single-point PSR mapping with reduced variability and shorter scan times relative to the full qMT model appears clinically feasible. (orig.)

  6. Glutamate may be an efferent transmitter that elicits inhibition in mouse taste buds.

    Directory of Open Access Journals (Sweden)

    Yijen A Huang

    Full Text Available Recent studies suggest that l-glutamate may be an efferent transmitter released from axons innervating taste buds. In this report, we determined the types of ionotropic synaptic glutamate receptors present on taste cells and that underlie this postulated efferent transmission. We also studied what effect glutamate exerts on taste bud function. We isolated mouse taste buds and taste cells, conducted functional imaging using Fura 2, and used cellular biosensors to monitor taste-evoked transmitter release. The findings show that a large fraction of Presynaptic (Type III taste bud cells (∼50% respond to 100 µM glutamate, NMDA, or kainic acid (KA with an increase in intracellular Ca(2+. In contrast, Receptor (Type II taste cells rarely (4% responded to 100 µM glutamate. At this concentration and with these compounds, these agonists activate glutamatergic synaptic receptors, not glutamate taste (umami receptors. Moreover, applying glutamate, NMDA, or KA caused taste buds to secrete 5-HT, a Presynaptic taste cell transmitter, but not ATP, a Receptor cell transmitter. Indeed, glutamate-evoked 5-HT release inhibited taste-evoked ATP secretion. The findings are consistent with a role for glutamate in taste buds as an inhibitory efferent transmitter that acts via ionotropic synaptic glutamate receptors.

  7. Glutamate may be an efferent transmitter that elicits inhibition in mouse taste buds.

    Science.gov (United States)

    Huang, Yijen A; Grant, Jeff; Roper, Stephen

    2012-01-01

    Recent studies suggest that l-glutamate may be an efferent transmitter released from axons innervating taste buds. In this report, we determined the types of ionotropic synaptic glutamate receptors present on taste cells and that underlie this postulated efferent transmission. We also studied what effect glutamate exerts on taste bud function. We isolated mouse taste buds and taste cells, conducted functional imaging using Fura 2, and used cellular biosensors to monitor taste-evoked transmitter release. The findings show that a large fraction of Presynaptic (Type III) taste bud cells (∼50%) respond to 100 µM glutamate, NMDA, or kainic acid (KA) with an increase in intracellular Ca(2+). In contrast, Receptor (Type II) taste cells rarely (4%) responded to 100 µM glutamate. At this concentration and with these compounds, these agonists activate glutamatergic synaptic receptors, not glutamate taste (umami) receptors. Moreover, applying glutamate, NMDA, or KA caused taste buds to secrete 5-HT, a Presynaptic taste cell transmitter, but not ATP, a Receptor cell transmitter. Indeed, glutamate-evoked 5-HT release inhibited taste-evoked ATP secretion. The findings are consistent with a role for glutamate in taste buds as an inhibitory efferent transmitter that acts via ionotropic synaptic glutamate receptors.

  8. Glutamate metabolism is down-regulated in astrocytes during experimental allergic encephalomyelitis

    DEFF Research Database (Denmark)

    Hardin-Pouzet, H; Krakowski, M; Bourbonnière, L

    1997-01-01

    dehydrogenase (GDH) expression were dramatically reduced. These two astrocytic enzymes are responsible for degradation of glutamate, the most abundant excitatory neurotransmitter in the brain. Since elevated levels of glutamate may be neurotoxic, we propose that the decreased capacity of astrocytes...... to metabolize glutamate may contribute to EAE pathology....

  9. Controls on Filling and Evacuation of Sediment in Waterfall Plunge Pools

    Science.gov (United States)

    Scheingross, J. S.; Lamb, M. P.

    2014-12-01

    Many waterfalls are characterized by the presence of deep plunge pools that experience periods of sediment fill and evacuation. These cycles of sediment fill are a first order control on the relative magnitude of lateral versus vertical erosion at the base of waterfalls, as vertical incision requires cover-free plunge pools to expose the bedrock floor, while lateral erosion can occur when pools are partially filled and plunge-pool walls are exposed. Currently, there exists no mechanistic model describing sediment transport through waterfall plunge pools, limiting our ability to predict waterfall retreat. To address this knowledge gap, we performed detailed laboratory experiments measuring plunge-pool sediment transport capacity (Qsc_pool) under varying waterfall and plunge-pool geometries, flow hydraulics, and sediment size. Our experimental plunge-pool sediment transport capacity measurements match well with a mechanistic model we developed which combines existing waterfall jet theory with a modified Rouse profile to predict sediment transport capacity as a function of water discharge and suspended sediment concentration at the plunge-pool lip. Comparing the transport capacity of plunge pools to lower gradient portions of rivers (Qsc_river) shows that, for transport limited conditions, plunge pools fill with sediment under modest water discharges when Qsc_river > Qsc_pool, and empty to bedrock under high discharges when Qsc_pool > Qsc_river. These results are consistent with field observations of sand-filled plunge pools with downstream boulder rims, implying filling and excavation of plunge pools over single-storm timescales. Thus, partial filling of waterfall plunge pools may provide a mechanism to promote lateral undercutting and retreat of waterfalls in homogeneous rock in which plunge-pool vertical incision occurs during brief large floods that expose bedrock, whereas lateral erosion may prevail during smaller events.

  10. Curcumin-Protected PC12 Cells Against Glutamate-Induced Oxidative Toxicity

    Directory of Open Access Journals (Sweden)

    Chi-Huang Chang

    2014-01-01

    Full Text Available Glutamate is a major excitatory neurotransmitter present in the central nervous system. The glutamate/cystine antiporter system xc– connects the antioxidant defense with neurotransmission and behaviour. Overactivation of ionotropic glutamate receptors induces neuronal death, a pathway called excitotoxicity. Glutamate-induced oxidative stress is a major contributor to neurodegenerative diseases including cerebral ischemia, Alzheimer’s and Huntington’s disease. Curcuma has a wide spectrum of biological activities regarding neuroprotection and neurocognition. By reducing the oxidative damage, curcumin attenuates a spinal cord ischemia-reperfusion injury, seizures and hippocampal neuronal loss. The rat pheochromocytoma (PC12 cell line exhibits many characteristics useful for the study of the neuroprotection and neurocognition. This investigation was carried out to determine whether the neuroprotective effects of curcumin can be observed via the glutamate-PC12 cell model. Results indicate that glutamate (20 mM upregulated glutathione peroxidase 1, glutathione disulphide, Ca2+ influx, nitric oxide production, cytochrome c release, Bax/Bcl-2 ratio, caspase-3 activity, lactate dehydrogenase release, reactive oxygen species, H2O2, and malondialdehyde; and downregulated glutathione, glutathione reductase, superoxide dismutase and catalase, resulting in enhanced cell apoptosis. Curcumin alleviates all these adverse effects. Conclusively, curcumin can effectively protect PC12 cells against the glutamate-induced oxidative toxicity. Its mode of action involves two pathways: the glutathione-dependent nitric oxide-reactive oxygen species pathway and the mitochondria-dependent nitric oxide-reactive oxygen species pathway.

  11. Creatine affords protection against glutamate-induced nitrosative and oxidative stress.

    Science.gov (United States)

    Cunha, Mauricio P; Lieberknecht, Vicente; Ramos-Hryb, Ana Belén; Olescowicz, Gislaine; Ludka, Fabiana K; Tasca, Carla I; Gabilan, Nelson H; Rodrigues, Ana Lúcia S

    2016-05-01

    Creatine has been reported to exert beneficial effects in several neurodegenerative diseases in which glutamatergic excitotoxicity and oxidative stress play an etiological role. The purpose of this study was to investigate the protective effects of creatine, as compared to the N-Methyl-d-Aspartate (NMDA) receptor antagonist dizocilpine (MK-801), against glutamate or hydrogen peroxide (H2O2)-induced injury in human neuroblastoma SH-SY5Y cells. Exposure of cells to glutamate (60-80 mM) or H2O2 (200-300 μM) for 24 h decreased cellular viability and increased dichlorofluorescein (DCF) fluorescence (indicative of increased reactive oxygen species, ROS) and nitric oxide (NO) production (assessed by mono-nitrogen oxides, NOx, levels). Creatine (1-10 mM) or MK-801 (0.1-10 μM) reduced glutamate- and H2O2-induced toxicity. The protective effect of creatine against glutamate-induced toxicity involves its antioxidant effect, since creatine, similar to MK-801, prevented the increase on DCF fluorescence induced by glutamate or H2O2. Furthermore, creatine or MK-801 blocked glutamate- and H2O2-induced increases in NOx levels. In another set of experiments, the repeated, but not acute, administration of creatine (300 mg/kg, po) in mice prevented the decreases on cellular viability and mitochondrial membrane potential (assessed by tetramethylrhodamine ethyl ester, TMRE, probe) of hippocampal slices incubated with glutamate (10 mM). Creatine concentration-dependent decreased the amount of nitrite formed in the reaction of oxygen with NO produced from sodium nitroprusside solution, suggesting that its protective effect against glutamate or H2O2-induced toxicity might be due to its scavenger activity. Overall, the results suggest that creatine may be useful as adjuvant therapy for neurodegenerative disease treatments. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Some Properties of Glutamate Dehydrogenase from the Marine Red ...

    African Journals Online (AJOL)

    Keywords: ammonia assimilation, glutamate dehydrogenase, GDH, Gracilaria sordida, red alga, enzyme activity. Glutamate dehydrogenases (GDH, EC ... Anabolic functions could be assimilation of ammonia released during photorespiration and synthesis of N-rich transport compounds. Western Indian Ocean Journal of ...

  13. Numerical Study of Condensation Heat Exchanger Design in a Subcooled Pool: Correlation Investigation

    International Nuclear Information System (INIS)

    Lee, Hee Joon; Ju, Yun Jae; Kang, Han Ok; Lee, Tae Ho; Park, Cheon Tae

    2012-01-01

    Generally the condensation heat exchanger has higher heat transfer coefficient compared to the single phase heat exchanger, so has been widely applied to the cooling systems of energy plant. Recently vertical or horizontal type condensation heat exchangers are being studied for the application to secondary passive cooling system of nuclear plants. Lee and Lee investigated the existing condensation correlation to the experiment for heat exchanger in saturated pool. They concluded Traviss' correlation showed most satisfactory results for the heat transfer coefficient and mass flow rate in a saturated water pool. In this study, a thermal sizing program of vertical condensation heat exchanger to design, TSCON(Thermal Sizing of CONdenser) was validated with the existing experimental data of condensation heat exchanger in a subcooled pool for pure steam condensation

  14. Risk-Conferring Glutamatergic Genes and Brain Glutamate Plus Glutamine in Schizophrenia

    Directory of Open Access Journals (Sweden)

    Juan R. Bustillo

    2017-06-01

    Full Text Available BackgroundThe proton magnetic resonance spectroscopy (1H-MRS signals from glutamate (or the combined glutamate and glutamine signal—Glx have been found to be greater in various brain regions in people with schizophrenia. Recently, the Psychiatric Genetics Consortium reported that several common single-nucleotide polymorphisms (SNPs in glutamate-related genes confer increased risk of schizophrenia. Here, we examined the relationship between presence of these risk polymorphisms and brain Glx levels in schizophrenia.Methods1H-MRS imaging data from an axial, supraventricular tissue slab were acquired in 56 schizophrenia patients and 67 healthy subjects. Glx was measured in gray matter (GM and white matter (WM regions. The genetic data included six polymorphisms genotyped across an Illumina 5M SNP array. Only three of six glutamate as well as calcium-related SNPs were available for examination. These included three glutamate-related polymorphisms (rs10520163 in CLCN3, rs12704290 in GRM3, and rs12325245 in SLC38A7, and three calcium signaling polymorphisms (rs1339227 in RIMS1, rs7893279 in CACNB2, and rs2007044 in CACNA1C. Summary risk scores for the three glutamate and the three calcium polymorphisms were calculated.ResultsGlx levels in GM positively correlated with glutamate-related genetic risk score but only in younger (≤36 years schizophrenia patients (p = 0.01. Glx levels did not correlate with calcium risk scores. Glx was higher in the schizophrenia group compared to levels in controls in GM and WM regardless of age (p < 0.001.ConclusionElevations in brain Glx are in part, related to common allelic variants of glutamate-related genes known to increase the risk for schizophrenia. Since the glutamate risk scores did not differ between groups, some other genetic or environmental factors likely interact with the variability in glutamate-related risk SNPs to contribute to an increase in brain Glx early in the illness.

  15. Pricing Electricity in Pools With Wind Producers

    DEFF Research Database (Denmark)

    Morales González, Juan Miguel; Conejo, A. J.; Kai Liu

    2012-01-01

    This paper considers an electricity pool that includes a significant number of wind producers and is cleared through a network-constrained auction, one day in advance and on an hourly basis. The hourly auction is formulated as a two-stage stochastic programming problem, where the first stage...... represents the clearing of the market and the second stage models the system operation under a number of plausible wind production realizations. This formulation co-optimizes energy and reserve, and allows deriving both pool energy prices and balancing energy prices. These prices result in both cost recovery...... for producers and revenue reconciliation. A case study of realistic size is used to illustrate the functioning of the proposed pricing scheme....

  16. Subcellular fractionation on Percoll gradient of mossy fiber synaptosomes: evoked release of glutamate, GABA, aspartate and glutamate decarboxylase activity in control and degranulated rat hippocampus.

    Science.gov (United States)

    Taupin, P; Ben-Ari, Y; Roisin, M P

    1994-05-02

    Using discontinuous density gradient centrifugation in isotonic Percoll sucrose, we have characterized two subcellular fractions (PII and PIII) enriched in mossy fiber synaptosomes and two others (SII and SIII) enriched in small synaptosomes. These synaptosomal fractions were compared with those obtained from adult hippocampus irradiated at neonatal stage to destroy granule cells and their mossy fibers. Synaptosomes were viable as judged by their ability to release aspartate, glutamate and GABA upon K+ depolarization. After irradiation, compared to the control values, the release of glutamate and GABA was decreased by 57 and 74% in the PIII fraction, but not in the other fractions and the content of glutamate, aspartate and GABA was also decreased in PIII fraction by 62, 44 and 52% respectively. These results suggest that mossy fiber (MF) synaptosomes contain and release glutamate and GABA. Measurement of the GABA synthesizing enzyme, glutamate decarboxylase, exhibited no significant difference after irradiation, suggesting that GABA is not synthesized by this enzyme in mossy fibers.

  17. Glutamate neurotransmission is affected in prenatally stressed offspring

    DEFF Research Database (Denmark)

    Adrover, Ezequiela; Pallarés, Maria Eugenia; Baier, Carlos Javier

    2015-01-01

    Previous studies from our laboratory have shown that male adult offspring of stressed mothers exhibited higher levels of ionotropic and metabotropic glutamate receptors than control rats. These offspring also showed long-lasting astroglial hypertrophy and a reduced dendritic arborization with syn......Previous studies from our laboratory have shown that male adult offspring of stressed mothers exhibited higher levels of ionotropic and metabotropic glutamate receptors than control rats. These offspring also showed long-lasting astroglial hypertrophy and a reduced dendritic arborization...... with synaptic loss. Since metabolism of glutamate is dependent on interactions between neurons and surrounding astroglia, our results suggest that glutamate neurotransmitter pathways might be impaired in the brain of prenatally stressed rats. To study the effect of prenatal stress on the metabolism...... was not affected it was found that prenatal stress (PS) changed the expression of the transporters, thus, producing a higher level of vesicular vGluT-1 in the frontal cortex (FCx) and elevated levels of GLT1 protein and messenger RNA in the hippocampus (HPC) of adult male PS offspring. We also observed increased...

  18. Glutamate modulation of GABA transport in retinal horizontal cells of the skate

    Science.gov (United States)

    Kreitzer, Matthew A; Andersen, Kristen A; Malchow, Robert Paul

    2003-01-01

    Transport of the amino acid GABA into neurons and glia plays a key role in regulating the effects of GABA in the vertebrate retina. We have examined the modulation of GABA-elicited transport currents of retinal horizontal cells by glutamate, the likely neurotransmitter of vertebrate photoreceptors. Enzymatically isolated external horizontal cells of skate were examined using whole-cell voltage-clamp techniques. GABA (1 mm) elicited an inward current that was completely suppressed by the GABA transport inhibitors tiagabine (10 μm) and SKF89976-A (100 μm), but was unaffected by 100 μm picrotoxin. Prior application of 100 μm glutamate significantly reduced the GABA-elicited current. Glutamate depressed the GABA dose-response curve without shifting the curve laterally or altering the voltage dependence of the current. The ionotropic glutamate receptor agonists kainate and AMPA also reduced the GABA-elicited current, and the effects of glutamate and kainate were abolished by the ionotropic glutamate receptor antagonist 6-cyano-7-nitroquinoxaline. NMDA neither elicited a current nor modified the GABA-induced current, and metabotropic glutamate analogues were also without effect. Inhibition of the GABA-elicited current by glutamate and kainate was reduced when extracellular calcium was removed and when recording pipettes contained high concentrations of the calcium chelator BAPTA. Caffeine (5 mm) and thapsigargin (2 nm), agents known to alter intracellular calcium levels, also reduced the GABA-elicited current, but increases in calcium induced by depolarization alone did not. Our data suggest that glutamate regulates GABA transport in retinal horizontal cells through a calcium-dependent process, and imply a close physical relationship between calcium-permeable glutamate receptors and GABA transporters in these cells. PMID:12562999

  19. Glutamate Concentration in the Superior Temporal Sulcus Relates to Neuroticism in Schizophrenia

    Directory of Open Access Journals (Sweden)

    Johanna Balz

    2018-05-01

    Full Text Available Clinical studies suggest aberrant neurotransmitter concentrations in the brains of patients with schizophrenia (SCZ. Numerous studies have indicated deviant glutamate concentrations in SCZ, although the findings are inconsistent. Moreover, alterations in glutamate concentrations could be linked to personality traits in SCZ. Here, we examined the relationships between personality dimensions and glutamate concentrations in a voxel encompassing the occipital cortex (OCC and another voxel encompassing the left superior temporal sulcus (STS. We used proton magnetic resonance spectroscopy to examine glutamate concentrations in the OCC and the STS in 19 SCZ and 21 non-psychiatric healthy control (HC participants. Personality dimensions neuroticism, extraversion, openness, agreeableness and conscientiousness were assessed using the NEO-FFI questionnaire. SCZ compared to HC showed higher glutamate concentrations in the STS, reduced extraversion scores, and enhanced neuroticism scores. No group differences were observed for the other personality traits and for glutamate concentrations in the OCC. For the SCZ group, glutamate concentrations in STS were negatively correlated with the neuroticism scores [r = -0.537, p = 0.018] but this was not found in HC [r(19 = 0.011, p = 0.962]. No other significant correlations were found. Our study showed an inverse relationship between glutamate concentrations in the STS and neuroticism scores in SCZ. Elevated glutamate in the STS might serve as a compensatory mechanism that enables patients with enhanced concentrations to control and prevent the expression of neuroticism.

  20. Aerosol Scrubbing Performance Test for Self-Priming Scrubbing Nozzle Submerged in Water Pool

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Doo Yong; Jung, Woo Young; Lee, Hyun Chul; Lee, Jong Chan; Kim, Gyu Tae; Song, Yong Jae [FNC Technology Co., Yongin (Korea, Republic of)

    2016-10-15

    A scrubbing nozzle is one of the key components for a wet scrubber process based Containment Filtered Venting System (CFVS). As a part of a development of Korean CFVS, a self-priming scrubbing nozzle shown in Fig. 1 has been developed based on the well-known venturi scrubber concept. The thermal-hydraulic performances such as the pressure drop across the nozzle, water suction behavior and droplet generation inside throat have been tested in the non-submerged condition as well as submerged condition. The self-priming scrubbing nozzle used for the wet scrubber based CFVS has been developed, which is submerged in the water pool. When there is gas flow at the inlet of the nozzle, the pool water is passively sucked from the water suction slit. The fine droplets generated inside the throat capture the aerosol particles and is discharged into the water pool. In the water pool, the pool scrubbing happens. The aerosol scrubbing performance tests for the developed self-priming scrubbing nozzle has been conducted under the operational conditions such as different aerosol sizes, different carrier gas steam fractions, different, different pool water level and nozzle inlet pressure. The major findings are as follows. (1) Aerosol scrubbing efficiency increases with the increase of the aerosol size. (2) Aerosol scrubbing efficiency increases with the increase of the carrier gas steam fraction. (3) Aerosol scrubbing.

  1. Aerosol Scrubbing Performance Test for Self-Priming Scrubbing Nozzle Submerged in Water Pool

    International Nuclear Information System (INIS)

    Lee, Doo Yong; Jung, Woo Young; Lee, Hyun Chul; Lee, Jong Chan; Kim, Gyu Tae; Song, Yong Jae

    2016-01-01

    A scrubbing nozzle is one of the key components for a wet scrubber process based Containment Filtered Venting System (CFVS). As a part of a development of Korean CFVS, a self-priming scrubbing nozzle shown in Fig. 1 has been developed based on the well-known venturi scrubber concept. The thermal-hydraulic performances such as the pressure drop across the nozzle, water suction behavior and droplet generation inside throat have been tested in the non-submerged condition as well as submerged condition. The self-priming scrubbing nozzle used for the wet scrubber based CFVS has been developed, which is submerged in the water pool. When there is gas flow at the inlet of the nozzle, the pool water is passively sucked from the water suction slit. The fine droplets generated inside the throat capture the aerosol particles and is discharged into the water pool. In the water pool, the pool scrubbing happens. The aerosol scrubbing performance tests for the developed self-priming scrubbing nozzle has been conducted under the operational conditions such as different aerosol sizes, different carrier gas steam fractions, different, different pool water level and nozzle inlet pressure. The major findings are as follows. (1) Aerosol scrubbing efficiency increases with the increase of the aerosol size. (2) Aerosol scrubbing efficiency increases with the increase of the carrier gas steam fraction. (3) Aerosol scrubbing

  2. MDMA decreases glutamic acid decarboxylase (GAD) 67-immunoreactive neurons in the hippocampus and increases seizure susceptibility: Role for glutamate.

    Science.gov (United States)

    Huff, Courtney L; Morano, Rachel L; Herman, James P; Yamamoto, Bryan K; Gudelsky, Gary A

    2016-12-01

    3,4-Methylenedioxy-methamphetamine (MDMA) is a unique psychostimulant that continues to be a popular drug of abuse. It has been well documented that MDMA reduces markers of 5-HT axon terminals in rodents, as well as humans. A loss of parvalbumin-immunoreactive (IR) interneurons in the hippocampus following MDMA treatment has only been documented recently. In the present study, we tested the hypothesis that MDMA reduces glutamic acid decarboxylase (GAD) 67-IR, another biochemical marker of GABA neurons, in the hippocampus and that this reduction in GAD67-IR neurons and an accompanying increase in seizure susceptibility involve glutamate receptor activation. Repeated exposure to MDMA (3×10mg/kg, ip) resulted in a reduction of 37-58% of GAD67-IR cells in the dentate gyrus (DG), CA1, and CA3 regions, as well as an increased susceptibility to kainic acid-induced seizures, both of which persisted for at least 30days following MDMA treatment. Administration of the NMDA antagonist MK-801 or the glutamate transporter type 1 (GLT-1) inducer ceftriaxone prevented both the MDMA-induced loss of GAD67-IR neurons and the increased vulnerability to kainic acid-induced seizures. The MDMA-induced increase in the extracellular concentration of glutamate in the hippocampus was significantly diminished in rats treated with ceftriaxone, thereby implicating a glutamatergic mechanism in the neuroprotective effects of ceftriaxone. In summary, the present findings support a role for increased extracellular glutamate and NMDA receptor activation in the MDMA-induced loss of hippocampal GAD67-IR neurons and the subsequent increased susceptibility to evoked seizures. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Glutamine and glutamate as vital metabolites

    Directory of Open Access Journals (Sweden)

    Newsholme P.

    2003-01-01

    Full Text Available Glucose is widely accepted as the primary nutrient for the maintenance and promotion of cell function. This metabolite leads to production of ATP, NADPH and precursors for the synthesis of macromolecules such as nucleic acids and phospholipids. We propose that, in addition to glucose, the 5-carbon amino acids glutamine and glutamate should be considered to be equally important for maintenance and promotion of cell function. The functions of glutamine/glutamate are many, i.e., they are substrates for protein synthesis, anabolic precursors for muscle growth, they regulate acid-base balance in the kidney, they are substrates for ureagenesis in the liver and for hepatic and renal gluconeogenesis, they act as an oxidative fuel for the intestine and cells of the immune system, provide inter-organ nitrogen transport, and act as precursors of neurotransmitter synthesis, of nucleotide and nucleic acid synthesis and of glutathione production. Many of these functions are interrelated with glucose metabolism. The specialized aspects of glutamine/glutamate metabolism of different glutamine-utilizing cells are discussed in the context of glucose requirements and cell function.

  4. Neuroprotective effects of α-iso-cubebenol on glutamate-induced neurotoxicity.

    Science.gov (United States)

    Park, Sun Young; Choi, Yung Hyun; Park, Geuntae; Choi, Young-Whan

    2015-09-01

    α-Iso-cubebenol is a natural compound isolated from Schisandra chinensis, and is reported to have beneficial bioactivity including anti-inflammatory and anti-tumor activities. Glutamate-induced oxidative neuronal damage has been implicated in a variety of neurodegenerative disorders. Here we investigated the mechanisms of α-iso-cubebenol protection of mouse hippocampus-derived neuronal cells (HT22 cells) from apoptotic cell death induced by the major excitatory neurotransmitter, glutamate. Pretreatment with α-iso-cubebenol markedly attenuated glutamate-induced loss of cell viability and release of lactate dehydrogenase), in a dose-dependent manner. α-Iso-cubebenol significantly reduced glutamate-induced intracellular reactive oxygen species and calcium accumulation. Strikingly, α-iso-cubebenol inhibited glutamate-induced mitochondrial depolarization, which releases apoptosis-inducing factor from mitochondria. α-Iso-cubebenol also suppressed glutamate-induced phosphorylation of extracellular-signal-regulated kinases. Furthermore, α-iso-cubebenol induced CREB phosphorylation and Nrf-2 nuclear accumulation and increased the promoter activity of ARE and CREB in HT22 cells. α-Iso-cubebenol also upregulated the expression of phase-II detoxifying/antioxidant enzymes such as HO-1 and NQO1. Subsequent studies revealed that the inhibitory effects of α-iso-cubebenol on glutamate-induced apoptosis were abolished by small interfering RNA-mediated knockdown of CREB and Nrf-2. These findings suggest that α-iso-cubebenol prevents excitotoxin-induced oxidative damage to neurons by inhibiting apoptotic cell death, and might be a potential preventive or therapeutic agent for neurodegenerative disorders. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Is glutamate involved in transient lower esophageal sphincter relaxations?

    NARCIS (Netherlands)

    Hirsch, D. P.; Tytgat, G. N. J.; Boeckxstaens, G. E. E.

    2002-01-01

    Glutamate is an important excitatory amino acid and plays a major role in brain stem neurotransmission. Although the effect of glutamate on esophaoreal motility is well studied, its role in the triggering of transient lower esophageal sphincter relaxations (TLESRs) remains to be determined.

  6. Synthesis and distribution of L-glutamic acid with three different labels

    International Nuclear Information System (INIS)

    Cohen, M.B.; Spolter, Leonard; Chia Chin Chang; MacDonald, N.S.

    1982-01-01

    A study was performed to compare the distribution of C-11 L-glutamic acid, labeled on the carboxyl group of either the alpha or gamma carbon with that of N-13 L-glutamic acid in order to determine if the position of the label is of importance in the study of the distribution of glutamic acid

  7. Mammalian folylpoly-γ-glutamate synthetase. 2. Substrate specificity and kinetic properties

    International Nuclear Information System (INIS)

    Cichowicz, D.J.; Shane, B.

    1987-01-01

    The specificity of hog liver folylpolyglutamate synthetase for folate substrates and for nucleotide and L-[ 14 C]glutamate substrates and analogues has been investigated. The kinetic mechanism, determined by using aminopterin as the folate substrate, is ordered Ter-Ter with MgATP binding first, folate second, and glutamate last. This mechanism precludes the sequential addition of glutamate moieties to enzyme-bound folate. Folate, dihydrofolate, and tetrahydrofolate possess the optimal configurations for catalysis while 5- and 10-position substitutions of the folate molecule impair catalysis. k/sub cat/ values decrease with increasing glutamate chain length, and the rate of decrease varies depending on the state of reduction and substitution of the folate molecule. Folate binding, as assessed by on rates, is slow. Dihydrofolate exhibits the fastest rate, and the rates are slightly reduced for tetrahydrofolate and 10-formyltetrahydrofolate and greatly reduced for 5-methyltetrahydrofolate and folic acid. Tetrahydrofolate polyglutamates are the only long glutamate chain length folates with detectable substrate activity. The specificity of the L-glutamate binding site is very narrow. L-Homocysteate and 4-threo-fluoroglutamate are alternate substrates and act as chain termination inhibitors in that their addition to the folate molecule prevents or severely retards the further addition of glutamate moieties. The K/sub m/ for glutamate is dependent on the folate substrate used. MgATP is the preferred nucleotide substrate, and β,γ-methylene-ATP, β,γ-imido-ATP, adenosine 5'-O-(3-thiotriphosphate), P 1 ,P 5 -di(adenosine-5') pentaphosphate, and free ATP 4- are potent inhibitors of the reaction

  8. Morphine Protects Spinal Cord Astrocytes from Glutamate-Induced Apoptosis via Reducing Endoplasmic Reticulum Stress

    Directory of Open Access Journals (Sweden)

    Chao Zhang

    2016-10-01

    Full Text Available Glutamate is not only a neurotransmitter but also an important neurotoxin in central nervous system (CNS. Chronic elevation of glutamate induces both neuronal and glial cell apoptosis. However, its effect on astrocytes is complex and still remains unclear. In this study, we investigated whether morphine, a common opioid ligand, could affect glutamate-induced apoptosis in astrocytes. Primary cultured astrocytes were incubated with glutamate in the presence/absence of morphine. It was found that morphine could reduce glutamate-induced apoptosis of astrocytes. Furthermore, glutamate activated Ca2+ release, thereby inducing endoplasmic reticulum (ER stress in astrocytes, while morphine attenuated this deleterious effect. Using siRNA to reduce the expression of κ-opioid receptor, morphine could not effectively inhibit glutamate-stimulated Ca2+ release in astrocytes, the protective effect of morphine on glutamate-injured astrocytes was also suppressed. These results suggested that morphine could protect astrocytes from glutamate-induced apoptosis via reducing Ca2+ overload and ER stress pathways. In conclusion, this study indicated that excitotoxicity participated in the glutamate mediated apoptosis in astrocytes, while morphine attenuated this deleterious effect via regulating Ca2+ release and ER stress.

  9. In vitro evidence for the brain glutamate efflux hypothesis

    DEFF Research Database (Denmark)

    Helms, Hans Christian; Madelung, Rasmus; Waagepetersen, Helle Sønderby

    2012-01-01

    resistance values of 1014 ± 70 O cm(2) , and (14) C-D-mannitol permeability values of 0.88 ± 0.13 × 10(-6) cm s(-1) . Unidirectional flux studies showed that L-aspartate and L-glutamate, but not D-aspartate, displayed polarized transport in the brain-to-blood direction, however, all three amino acids......The concentration of the excitotoxic amino acid, L-glutamate, in brain interstitial fluid is tightly regulated by uptake transporters and metabolism in astrocytes and neurons. The aim of this study was to investigate the possible role of the blood-brain barrier endothelium in brain L......-glutamate homeostasis. Transendothelial transport- and accumulation studies of (3) H-L-glutamate, (3) H-L-aspartate, and (3) H-D-aspartate in an electrically tight bovine endothelial/rat astrocyte blood-brain barrier coculture model were performed. After 6 days in culture, the endothelium displayed transendothelial...

  10. GMP reverses the facilitatory effect of glutamate on inhibitory avoidance task in rats.

    Science.gov (United States)

    Rubin, M A; Jurach, A; da Costa Júnior, E M; Lima, T T; Jiménez-Bernal, R E; Begnini, J; Souza, D O; de Mello, C F

    1996-09-02

    Previous studies have demonstrated that post-training intrahippocampal glutamate administration improves inhibitory avoidance task performance in rats. Antagonism of the agonist actions of glutamate by guanine nucleotides has been shown at the molecular and behavioural level. In the present investigation we demonstrate that intrahippocampal co-administration of GMP (guanosine 5'-monophosphate) reverses the facilitatory effect of glutamate on the inhibitory avoidance learning paradigm and inhibits [3H]glutamate binding in hippocampal synaptic plasma membranes. These results suggest that guanine nucleotides may modulate glutamate actions.

  11. Microscopic picture of the aqueous solvation of glutamic acid

    NARCIS (Netherlands)

    Leenders, E.J.M.; Bolhuis, P.G.; Meijer, E.J.

    2008-01-01

    We present molecular dynamics simulations of glutamic acid and glutamate solvated in water, using both density functional theory (DFT) and the Gromos96 force field. We focus on the microscopic aspects of the solvation−particularly on the hydrogen bond structures and dynamics−and investigate the

  12. Poly-gamma-glutamic acid a substitute of salivary protein statherin

    International Nuclear Information System (INIS)

    Qamar, Z.; Rahim, Z.B.H.A.; Fatima, T.

    2016-01-01

    The modus operandi of salivary proteins in reducing the kinetics of enamel dissolution during simulated caries challenges is thought to be associated with interaction of glutamic acid residues with human teeth surfaces. Japanese traditional food stuff natto is rich with chain of repeating glutamic acid residues linked by gamma-peptide bond and hence, named poly-gamma-glutamic acid (PGGA). It is a naturally occurring polypeptide and may therefore perform similar caries inhibitory functions as statherin. (author)

  13. Monosodium glutamate neonatal treatment induces cardiovascular autonomic function changes in rodents

    Directory of Open Access Journals (Sweden)

    Signorá Peres Konrad

    2012-10-01

    Full Text Available OBJECTIVES: The aim of this study was to evaluate cardiovascular autonomic function in a rodent obesity model induced by monosodium glutamate injections during the first seven days of life. METHOD: The animals were assigned to control (control, n = 10 and monosodium glutamate (monosodium glutamate, n = 13 groups. Thirty-three weeks after birth, arterial and venous catheters were implanted for arterial pressure measurements, drug administration, and blood sampling. Baroreflex sensitivity was evaluated according to the tachycardic and bradycardic responses induced by sodium nitroprusside and phenylephrine infusion, respectively. Sympathetic and vagal effects were determined by administering methylatropine and propranolol. RESULTS: Body weight, Lee index, and epididymal white adipose tissue values were higher in the monosodium glutamate group in comparison to the control group. The monosodium glutamate-treated rats displayed insulin resistance, as shown by a reduced glucose/insulin index (-62.5%, an increased area under the curve of total insulin secretion during glucose overload (39.3%, and basal hyperinsulinemia. The mean arterial pressure values were higher in the monosodium glutamate rats, whereas heart rate variability (>7 times, bradycardic responses (>4 times, and vagal (~38% and sympathetic effects (~36% were reduced as compared to the control group. CONCLUSION: Our results suggest that obesity induced by neonatal monosodium glutamate treatment impairs cardiac autonomic function and most likely contributes to increased arterial pressure and insulin resistance.

  14. Feedback-induced glutamate spillover enhances negative feedback from horizontal cells to cones

    NARCIS (Netherlands)

    Vroman, Rozan; Kamermans, M.

    2015-01-01

    KEY POINTS: In the retina, horizontal cells feed back negatively to cone photoreceptors. Glutamate released from cones can spill over to neighbouring cones. Here we show that cone glutamate release induced by negative feedback can also spill over to neighbouring cones. This glutamate activates the

  15. The dissolution of natural and artificial dusts in glutamic acid

    Science.gov (United States)

    Ling, Zhang; Faqin, Dong; Xiaochun, He

    2015-06-01

    This article describes the characteristics of natural dusts, industrial dusts, and artificial dusts, such as mineral phases, chemical components, morphological observation and size. Quartz and calcite are the main phases of natural dusts and industrial dusts with high SiO2 and CaO and low K2O and Na2O in the chemical composition. The dissolution and electrochemical action of dusts in glutamic acid liquor at the simulated human body temperature (37 °C) in 32 h was investigated. The potential harm that the dust could lead to in body glutamic acid acidic environment, namely biological activity, is of great importance for revealing the human toxicological mechanism. The changes of pH values and electric conductivity of suspension of those dusts were similar, increased slowly in the first 8 h, and then the pH values increased rapidly. The total amount of dissolved ions of K, Ca, Na, and Mg was 35.4 to 429 mg/kg, particularly Ca was maximal of 20 to 334 mg/kg. The total amount of dissolved ions of Fe, Zn, Mn, Pb, and Ba was 0.18 to 5.59 mg/kg and in Al and Si was 3.0 to 21.7 mg/kg. The relative solubility order of dusts in glutamic acid is wollastonite > serpentine > sepiolite, the cement plant industrial dusts > natural dusts > power plant industrial dusts. The wollastonite and cement plant industrial dusts have the highest solubility, which also have high content of CaO; this shows that there are a poorer corrosion-resisting ability and lower bio-resistibility. Sepiolite and power plant industrial dusts have lowest solubility, which also have high content of SiO2; this shows that there are a higher corrosion-resisting ability and stronger bio-resistibility.

  16. Response of hippocampal mossy fiber zinc to excessive glutamate release.

    Science.gov (United States)

    Takeda, Atsushi; Minami, Akira; Sakurada, Naomi; Nakajima, Satoko; Oku, Naoto

    2007-01-01

    The response of hippocampal mossy fiber zinc to excessive glutamate release was examined to understand the role of the zinc in excessive excitation in the hippocampus. Extracellular zinc and glutamate concentrations during excessive stimulation with high K(+) were compared between the hippocampal CA3 and CA1 by the in vivo microdialysis. Zinc concentration in the CA3 was more increased than that in the CA1, while glutamate concentration in the CA3 was less increased than that in the CA1. It is likely that more increase in extracellular zinc is linked with less increase in extracellular glutamate in the CA3. To see zinc action in mossy fiber synapses during excessive excitation, furthermore, 1mM glutamate was regionally delivered to the stratum lucidum in the presence of zinc or CaEDTA, a membrane-impermeable zinc chelator, and intracellular calcium signal was measured in the CA3 pyramidal cell layer. The persistent increase in calcium signal during stimulation with glutamate was significantly attenuated in the presence of 100 microM zinc, while significantly enhanced in the presence of 1mM CaEDTA. These results suggest that zinc released from mossy fibers attenuates the increase in intracellular calcium signal in mossy fiber synapses and postsynaptic CA3 neurons after excessive inputs to dentate granular cells.

  17. Excretion and intestinal absorption of tritiated glutamic acid by carp, Cyprinus Carpio

    International Nuclear Information System (INIS)

    Watabe, Terushia; Kistner, G.

    1986-01-01

    Excretion and intestinal absorption of tritiated glutamic acid by carp was investigated. Approximately 80% of orally administered tritium was excreted at a half life value of 1.4 h and an observed slower excretion of 7 days for the remainder. Tritium incorporated in glutamic acid was efficiently retained at the site of absorption, i.e. intestine, liver, gill, kidney, blood and muscle. A dual marking experiment using tritiated glutamic acid and 14 C-market glutamic acid showed higher excretion of tritium by factors 2.0 to 4.9 than that of 14 C. Tritiated glutamic acid is considered to be mainly incorporated in the citric acid cycle soon after administration and the release of tritium in tritiated water through the cycle is assumed as causing the initial rapid excretion of tritium in carp. The intestinal absorption of glutamic acid was likely to depend on its concentration in the administered solution. The maximum level of absorption is estimated to be 0.1 m mol/0.5 h for one year old carp. The results obtained here would make it possible to estimate the tritium contamination of fish due to tritiated glutamic acid entering the food chain. (orig.)

  18. Surface grafting of poly(L-glutamates). 3. Block copolymerization

    NARCIS (Netherlands)

    Wieringa, RH; Siesling, EA; Werkman, PJ; Vorenkamp, EJ; Schouten, AJ

    2001-01-01

    This paper describes for the first time the synthesis of surface-grafted AB-block copolypeptides, consisting of poly(gamma -benzyl L-glutamate) (PBLG) as the A-block and poly(gamma -methyl L-glutamate) (PMLG) as the B-block. Immobilized primary amine groups of (,gamma -aminopropyl)triethoxysilane

  19. In vitro evidence for the brain glutamate efflux hypothesis: brain endothelial cells cocultured with astrocytes display a polarized brain-to-blood transport of glutamate.

    Science.gov (United States)

    Helms, Hans Christian; Madelung, Rasmus; Waagepetersen, Helle Sønderby; Nielsen, Carsten Uhd; Brodin, Birger

    2012-05-01

    The concentration of the excitotoxic amino acid, L-glutamate, in brain interstitial fluid is tightly regulated by uptake transporters and metabolism in astrocytes and neurons. The aim of this study was to investigate the possible role of the blood-brain barrier endothelium in brain L-glutamate homeostasis. Transendothelial transport- and accumulation studies of (3) H-L-glutamate, (3) H-L-aspartate, and (3) H-D-aspartate in an electrically tight bovine endothelial/rat astrocyte blood-brain barrier coculture model were performed. After 6 days in culture, the endothelium displayed transendothelial resistance values of 1014 ± 70 Ω cm(2) , and (14) C-D-mannitol permeability values of 0.88 ± 0.13 × 10(-6) cm s(-1) . Unidirectional flux studies showed that L-aspartate and L-glutamate, but not D-aspartate, displayed polarized transport in the brain-to-blood direction, however, all three amino acids accumulated in the cocultures when applied from the abluminal side. The transcellular transport kinetics were characterized with a K(m) of 69 ± 15 μM and a J(max) of 44 ± 3.1 pmol min(-1) cm(-2) for L-aspartate and a K(m) of 138 ± 49 μM and J(max) of 28 ± 3.1 pmol min(-1) cm(-2) for L-glutamate. The EAAT inhibitor, DL-threo-ß-Benzyloxyaspartate, inhibited transendothelial brain-to-blood fluxes of L-glutamate and L-aspartate. Expression of EAAT-1 (Slc1a3), -2 (Slc1a2), and -3 (Slc1a1) mRNA in the endothelial cells was confirmed by conventional PCR and localization of EAAT-1 and -3 in endothelial cells was shown with immunofluorescence. Overall, the findings suggest that the blood-brain barrier itself may participate in regulating brain L-glutamate concentrations. Copyright © 2012 Wiley Periodicals, Inc.

  20. Glutamate mediated astrocytic filtering of neuronal activity.

    Directory of Open Access Journals (Sweden)

    Gilad Wallach

    2014-12-01

    Full Text Available Neuron-astrocyte communication is an important regulatory mechanism in various brain functions but its complexity and role are yet to be fully understood. In particular, the temporal pattern of astrocyte response to neuronal firing has not been fully characterized. Here, we used neuron-astrocyte cultures on multi-electrode arrays coupled to Ca2+ imaging and explored the range of neuronal stimulation frequencies while keeping constant the amount of stimulation. Our results reveal that astrocytes specifically respond to the frequency of neuronal stimulation by intracellular Ca2+ transients, with a clear onset of astrocytic activation at neuron firing rates around 3-5 Hz. The cell-to-cell heterogeneity of the astrocyte Ca2+ response was however large and increasing with stimulation frequency. Astrocytic activation by neurons was abolished with antagonists of type I metabotropic glutamate receptor, validating the glutamate-dependence of this neuron-to-astrocyte pathway. Using a realistic biophysical model of glutamate-based intracellular calcium signaling in astrocytes, we suggest that the stepwise response is due to the supralinear dynamics of intracellular IP3 and that the heterogeneity of the responses may be due to the heterogeneity of the astrocyte-to-astrocyte couplings via gap junction channels. Therefore our results present astrocyte intracellular Ca2+ activity as a nonlinear integrator of glutamate-dependent neuronal activity.

  1. Glutamate Mediated Astrocytic Filtering of Neuronal Activity

    Science.gov (United States)

    Herzog, Nitzan; De Pittà, Maurizio; Jacob, Eshel Ben; Berry, Hugues; Hanein, Yael

    2014-01-01

    Neuron-astrocyte communication is an important regulatory mechanism in various brain functions but its complexity and role are yet to be fully understood. In particular, the temporal pattern of astrocyte response to neuronal firing has not been fully characterized. Here, we used neuron-astrocyte cultures on multi-electrode arrays coupled to Ca2+ imaging and explored the range of neuronal stimulation frequencies while keeping constant the amount of stimulation. Our results reveal that astrocytes specifically respond to the frequency of neuronal stimulation by intracellular Ca2+ transients, with a clear onset of astrocytic activation at neuron firing rates around 3-5 Hz. The cell-to-cell heterogeneity of the astrocyte Ca2+ response was however large and increasing with stimulation frequency. Astrocytic activation by neurons was abolished with antagonists of type I metabotropic glutamate receptor, validating the glutamate-dependence of this neuron-to-astrocyte pathway. Using a realistic biophysical model of glutamate-based intracellular calcium signaling in astrocytes, we suggest that the stepwise response is due to the supralinear dynamics of intracellular IP3 and that the heterogeneity of the responses may be due to the heterogeneity of the astrocyte-to-astrocyte couplings via gap junction channels. Therefore our results present astrocyte intracellular Ca2+ activity as a nonlinear integrator of glutamate-dependent neuronal activity. PMID:25521344

  2. Brain glutamine synthesis requires neuronal-born aspartate as amino donor for glial glutamate formation.

    Science.gov (United States)

    Pardo, Beatriz; Rodrigues, Tiago B; Contreras, Laura; Garzón, Miguel; Llorente-Folch, Irene; Kobayashi, Keiko; Saheki, Takeyori; Cerdan, Sebastian; Satrústegui, Jorgina

    2011-01-01

    The glutamate-glutamine cycle faces a drain of glutamate by oxidation, which is balanced by the anaplerotic synthesis of glutamate and glutamine in astrocytes. De novo synthesis of glutamate by astrocytes requires an amino group whose origin is unknown. The deficiency in Aralar/AGC1, the main mitochondrial carrier for aspartate-glutamate expressed in brain, results in a drastic fall in brain glutamine production but a modest decrease in brain glutamate levels, which is not due to decreases in neuronal or synaptosomal glutamate content. In vivo (13)C nuclear magnetic resonance labeling with (13)C(2)acetate or (1-(13)C) glucose showed that the drop in brain glutamine is due to a failure in glial glutamate synthesis. Aralar deficiency induces a decrease in aspartate content, an increase in lactate production, and lactate-to-pyruvate ratio in cultured neurons but not in cultured astrocytes, indicating that Aralar is only functional in neurons. We find that aspartate, but not other amino acids, increases glutamate synthesis in both control and aralar-deficient astrocytes, mainly by serving as amino donor. These findings suggest the existence of a neuron-to-astrocyte aspartate transcellular pathway required for astrocyte glutamate synthesis and subsequent glutamine formation. This pathway may provide a mechanism to transfer neuronal-born redox equivalents to mitochondria in astrocytes.

  3. Hispidulin inhibits the release of glutamate in rat cerebrocortical nerve terminals

    International Nuclear Information System (INIS)

    Lin, Tzu-Yu; Lu, Cheng-Wei; Wang, Chia-Chuan; Lu, Jyh-Feng; Wang, Su-Jane

    2012-01-01

    Hispidulin, a naturally occurring flavone, has been reported to have an antiepileptic profile. An excessive release of glutamate is considered to be related to neuropathology of epilepsy. We investigated whether hispidulin affected endogenous glutamate release in rat cerebral cortex nerve terminals (synaptosomes) and explored the possible mechanism. Hispidulin inhibited the release of glutamate evoked by the K + channel blocker 4-aminopyridine (4-AP). The effects of hispidulin on the evoked glutamate release were prevented by the chelation of extracellular Ca 2+ ions and the vesicular transporter inhibitor bafilomycin A1. However, the glutamate transporter inhibitor DL-threo-beta-benzyl-oxyaspartate did not have any effect on hispidulin action. Hispidulin reduced the depolarization-induced increase in cytosolic free Ca 2+ concentration ([Ca 2+ ] C ), but did not alter 4-AP-mediated depolarization. Furthermore, the effect of hispidulin on evoked glutamate release was abolished by blocking the Ca v 2.2 (N-type) and Ca v 2.1 (P/Q-type) channels, but not by blocking ryanodine receptors or mitochondrial Na + /Ca 2+ exchange. Mitogen-activated protein kinase kinase (MEK) inhibition also prevented the inhibitory effect of hispidulin on evoked glutamate release. Western blot analyses showed that hispidulin decreased the 4-AP-induced phosphorylation of extracellular signal-regulated kinase 1 and 2 (ERK1/2) and synaptic vesicle-associated protein synapsin I, a major presynaptic substrate for ERK; this decrease was also blocked by the MEK inhibitor. Moreover, the inhibition of glutamate release by hispidulin was strongly attenuated in mice without synapsin I. These results show that hispidulin inhibits glutamate release from cortical synaptosomes in rats through the suppression of presynaptic voltage-dependent Ca 2+ entry and ERK/synapsin I signaling pathway. -- Highlights: ► Hispidulin inhibited glutamate release from rat cerebrocortical synaptosomes. ► This action did

  4. Hispidulin inhibits the release of glutamate in rat cerebrocortical nerve terminals

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Tzu-Yu [Department of Anesthesiology, Far-Eastern Memorial Hospital, Pan-Chiao District, New Taipei, 22060, Taiwan (China); Department of Mechanical Engineering, Yuan Ze University, Taoyuan, 320, Taiwan (China); Lu, Cheng-Wei [Department of Anesthesiology, Far-Eastern Memorial Hospital, Pan-Chiao District, New Taipei, 22060, Taiwan (China); Wang, Chia-Chuan; Lu, Jyh-Feng [School of Medicine, Fu Jen Catholic University, No.510, Zhongzheng Rd., Xinzhuang Dist., New Taipei, 24205, Taiwan (China); Wang, Su-Jane, E-mail: med0003@mail.fju.edu.tw [Graduate Institute of Basic Medicine, Fu Jen Catholic University, No.510, Zhongzheng Rd., Xinzhuang Dist., New Taipei, 24205, Taiwan (China); School of Medicine, Fu Jen Catholic University, No.510, Zhongzheng Rd., Xinzhuang Dist., New Taipei, 24205, Taiwan (China)

    2012-09-01

    Hispidulin, a naturally occurring flavone, has been reported to have an antiepileptic profile. An excessive release of glutamate is considered to be related to neuropathology of epilepsy. We investigated whether hispidulin affected endogenous glutamate release in rat cerebral cortex nerve terminals (synaptosomes) and explored the possible mechanism. Hispidulin inhibited the release of glutamate evoked by the K{sup +} channel blocker 4-aminopyridine (4-AP). The effects of hispidulin on the evoked glutamate release were prevented by the chelation of extracellular Ca{sup 2+} ions and the vesicular transporter inhibitor bafilomycin A1. However, the glutamate transporter inhibitor DL-threo-beta-benzyl-oxyaspartate did not have any effect on hispidulin action. Hispidulin reduced the depolarization-induced increase in cytosolic free Ca{sup 2+} concentration ([Ca{sup 2+}]{sub C}), but did not alter 4-AP-mediated depolarization. Furthermore, the effect of hispidulin on evoked glutamate release was abolished by blocking the Ca{sub v}2.2 (N-type) and Ca{sub v}2.1 (P/Q-type) channels, but not by blocking ryanodine receptors or mitochondrial Na{sup +}/Ca{sup 2+} exchange. Mitogen-activated protein kinase kinase (MEK) inhibition also prevented the inhibitory effect of hispidulin on evoked glutamate release. Western blot analyses showed that hispidulin decreased the 4-AP-induced phosphorylation of extracellular signal-regulated kinase 1 and 2 (ERK1/2) and synaptic vesicle-associated protein synapsin I, a major presynaptic substrate for ERK; this decrease was also blocked by the MEK inhibitor. Moreover, the inhibition of glutamate release by hispidulin was strongly attenuated in mice without synapsin I. These results show that hispidulin inhibits glutamate release from cortical synaptosomes in rats through the suppression of presynaptic voltage-dependent Ca{sup 2+} entry and ERK/synapsin I signaling pathway. -- Highlights: ► Hispidulin inhibited glutamate release from rat

  5. Real-time monitoring of extracellular l-glutamate levels released by high-frequency stimulation at region CA1 of hippocampal slices with a glass capillary-based l-glutamate sensor

    Directory of Open Access Journals (Sweden)

    Yuki Ikegami

    2014-12-01

    Full Text Available Real-time monitoring of l-glutamate released by high-frequency stimulation in region CA1 of mouse hippocampal slices was performed with a glass capillary-based sensor, in combination with the recoding of excitatory postsynaptic potentials (fEPSPs. A method for extracting l-glutamate currents from the recorded ones was described and applied for determining the level of extracellular l-glutamate released by 100 Hz stimulation. Recording of an l-glutamate current with a current sampling interval of 1 Hz was found to be useful for acquiring a Faradaic current that reflects l-glutamate level released by the high-frequency stimulation of 7 trains, each 20 stimuli at 100 Hz and inter-train interval of 3 s. The l-glutamate level was obtained as 15 ± 6 μM (n = 8 for the persistent enhancement of fEPSPs, i.e., the induction of long-term potentiation (LTP, and 3 ± 1 μM (n = 5 for the case of no LTP induction. Based on these observations, the level of the extracellular l-glutamate was shown to play a crucial role in the induction of LTP.

  6. 78 FR 76321 - Monosodium Glutamate From China and Indonesia

    Science.gov (United States)

    2013-12-17

    ... (Preliminary)] Monosodium Glutamate From China and Indonesia Determinations On the basis of the record \\1... injured by reason of imports from China and Indonesia of monosodium glutamate, provided for in subheading... United States at less than fair value (LTFV) and subsidized by the Governments of China and Indonesia. \\1...

  7. GDH-Dependent Glutamate Oxidation in the Brain Dictates Peripheral Energy Substrate Distribution

    DEFF Research Database (Denmark)

    Karaca, Melis; Frigerio, Francesca; Migrenne, Stephanie

    2015-01-01

    in a central energy-deprivation state with increased ADP/ATP ratios and phospho-AMPK in the hypothalamus. This induced changes in the autonomous nervous system balance, with increased sympathetic activity promoting hepatic glucose production and mobilization of substrates reshaping peripheral energy stores...... glutamate dehydrogenase (GDH) activity. Here, we investigated the significance of glutamate as energy substrate for the brain. Upon glutamate exposure, astrocytes generated ATP in a GDH-dependent way. The observed lack of glutamate oxidation in brain-specific GDH null CnsGlud1(-/-) mice resulted...

  8. The 'glial' glutamate transporter, EAAT2 (Glt-1) accounts for high affinity glutamate uptake into adult rodent nerve endings.

    Science.gov (United States)

    Suchak, Sachin K; Baloyianni, Nicoletta V; Perkinton, Michael S; Williams, Robert J; Meldrum, Brian S; Rattray, Marcus

    2003-02-01

    The excitatory amino acid transporters (EAAT) removes neurotransmitters glutamate and aspartate from the synaptic cleft. Most CNS glutamate uptake is mediated by EAAT2 into glia, though nerve terminals show evidence for uptake, through an unknown transporter. Reverse-transcriptase PCR identified the expression of EAAT1, EAAT2, EAAT3 and EAAT4 mRNAs in primary cultures of mouse cortical or striatal neurones. We have used synaptosomes and glial plasmalemmal vesicles (GPV) from adult mouse and rat CNS to identify the nerve terminal transporter. Western blotting showed detectable levels of the transporters EAAT1 (GLAST) and EAAT2 (Glt-1) in both synaptosomes and GPVs. Uptake of [3H]D-aspartate or [3H]L-glutamate into these preparations revealed sodium-dependent uptake in GPV and synaptosomes which was inhibited by a range of EAAT blockers: dihydrokainate, serine-o-sulfate, l-trans-2,4-pyrrolidine dicarboxylate (PDC) (+/-)-threo-3-methylglutamate and (2S,4R )-4-methylglutamate. The IC50 values found for these compounds suggested functional expression of the 'glial, transporter, EAAT2 in nerve terminals. Additionally blockade of the majority EAAT2 uptake sites with 100 micro m dihydrokainate, failed to unmask any functional non-EAAT2 uptake sites. The data presented in this study indicate that EAAT2 is the predominant nerve terminal glutamate transporter in the adult rodent CNS.

  9. Peri-adolescent drinking of ethanol and/or nicotine modulates astroglial glutamate transporters and metabotropic glutamate receptor-1 in female alcohol-preferring rats.

    Science.gov (United States)

    Alasmari, Fawaz; Bell, Richard L; Rao, P S S; Hammad, Alaa M; Sari, Youssef

    2018-07-01

    Impairment in glutamate neurotransmission mediates the development of dependence upon nicotine (NIC) and ethanol (EtOH). Previous work indicates that continuous access to EtOH or phasic exposure to NIC reduces expression of the glutamate transporter-1 (GLT-1) and cystine/glutamate antiporter (xCT) but not the glutamate/aspartate transporter (GLAST). Additionally, metabotropic glutamate receptors (mGluRs) expression was affected following exposure to EtOH or NIC. However, little is known about the effects of EtOH and NIC co-consumption on GLT-1, xCT, GLAST, and mGluR1 expression. In this study, peri-adolescent female alcohol preferring (P) rats were given binge-like access to water, sucrose (SUC), SUC-NIC, EtOH, or EtOH-NIC for four weeks. The present study determined the effects of these reinforcers on GLT-1, xCT, GLAST, and mGluR1 expression in the nucleus accumbens (NAc), hippocampus (HIP) and prefrontal cortex (PFC). GLT-1 and xCT expression were decreased in the NAc following both SUC-NIC and EtOH-NIC. In addition, only xCT expression was downregulated in the HIP in both of these latter groups. Also, glutathione peroxidase (GPx) activity in the HIP was reduced following SUC, SUC-NIC, EtOH, and EtOH-NIC consumption. Similar to previous work, GLAST expression was not altered in any brain region by any of the reinforcers. However, mGluR1 expression was increased in the NAc in the SUC-NIC, EtOH, and EtOH-NIC groups. These results indicate that peri-adolescent binge-like drinking of EtOH or SUC with or without NIC may exert differential effects on astroglial glutamate transporters and receptors. Our data further parallel some of the previous findings observed in adult rats. Copyright © 2018. Published by Elsevier Inc.

  10. Prefrontal cortex glutamate correlates with mental perspective-taking.

    Directory of Open Access Journals (Sweden)

    Christiane Montag

    Full Text Available BACKGROUND: Dysfunctions in theory of mind and empathic abilities have been suggested as core symptoms in major psychiatric disorders including schizophrenia and autism. Since self monitoring, perspective taking and empathy have been linked to prefrontal (PFC and anterior cingulate cortex (ACC function, neurotransmitter variations in these areas may account for normal and pathological variations of these functions. Converging evidence indicates an essential role of glutamatergic neurotransmission in psychiatric diseases with pronounced deficits in empathy. However, the role of the glutamate system for different dimensions of empathy has not been investigated so far. METHODOLOGY/PRINCIPAL FINDINGS: Absolute concentrations of cerebral glutamate in the ACC, left dorsolateral PFC and left hippocampus were determined by 3-tesla proton magnetic resonance spectroscopy (1H-MRS in 17 healthy individuals. Three dimensions of empathy were estimated by a self-rating questionnaire, the Interpersonal Reactivity Index (IRI. Linear regression analysis showed that dorsolateral PFC glutamate concentration was predicted by IRI factor "perspective taking" (T = -2.710, p = 0.018; adjusted alpha-level of 0.017, Bonferroni but not by "empathic concern" or "personal distress". No significant relationship between IRI subscores and the glutamate levels in the ACC or left hippocampus was detected. CONCLUSIONS/SIGNIFICANCE: This is the first study to investigate the role of the glutamate system for dimensions of theory of mind and empathy. Results are in line with recent concepts that executive top-down control of behavior is mediated by prefrontal glutamatergic projections. This is a preliminary finding that needs a replication in an independent sample.

  11. Core disruptive accident and recriticality analysis with FX2-POOL

    International Nuclear Information System (INIS)

    Abramson, P.B.

    1976-01-01

    The current state of development of FX2-POOL, a two-dimensional hydrodynamic, thermodynamic and neutronic scoping model for Hypothetical Core Disruptive Accident analysis is described. Checkout comparisons to VENUS for prompt burst conditions were good. Use of FX2-POOL to examine the importance of fuel to steel heat transfer during a prompt burst indicates that heat transfer plays no important role on that time scale. Scoping studies of material thermohydrodynamics for about 20 to 30 milliseconds following the prompt burst indicate that heat transfer is important on the time scale necessary for the CDA bubble to grow to the size of the original core. Preliminary results are presented for energetics of boiling fuel steel pools which are forced recritical by local surface pressurization

  12. 40 CFR 721.3820 - L-Glutamic acid, N-(1-oxododecyl)-, disodium salt.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false L-Glutamic acid, N-(1-oxododecyl... Specific Chemical Substances § 721.3820 L-Glutamic acid, N-(1-oxododecyl)-, disodium salt. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as L-Glutamic...

  13. Hierarchical mutational events compensate for glutamate auxotrophy of a Bacillus subtilis gltC mutant.

    Science.gov (United States)

    Dormeyer, Miriam; Lübke, Anastasia L; Müller, Peter; Lentes, Sabine; Reuß, Daniel R; Thürmer, Andrea; Stülke, Jörg; Daniel, Rolf; Brantl, Sabine; Commichau, Fabian M

    2017-06-01

    Glutamate is the major donor of nitrogen for anabolic reactions. The Gram-positive soil bacterium Bacillus subtilis either utilizes exogenously provided glutamate or synthesizes it using the gltAB-encoded glutamate synthase (GOGAT). In the absence of glutamate, the transcription factor GltC activates expression of the GOGAT genes for glutamate production. Consequently, a gltC mutant strain is auxotrophic for glutamate. Using a genetic selection and screening system, we could isolate and differentiate between gltC suppressor mutants in one step. All mutants had acquired the ability to synthesize glutamate, independent of GltC. We identified (i) gain-of-function mutations in the gltR gene, encoding the transcription factor GltR, (ii) mutations in the promoter of the gltAB operon and (iii) massive amplification of the genomic locus containing the gltAB operon. The mutants belonging to the first two classes constitutively expressed the gltAB genes and produced sufficient glutamate for growth. By contrast, mutants that belong to the third class appeared most frequently and solved glutamate limitation by increasing the copy number of the poorly expressed gltAB genes. Thus, glutamate auxotrophy of a B. subtilis gltC mutant can be relieved in multiple ways. Moreover, recombination-dependent amplification of the gltAB genes is the predominant mutational event indicating a hierarchy of mutations. © 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.

  14. Backpropagating Action Potentials Enable Detection of Extrasynaptic Glutamate by NMDA Receptors

    Directory of Open Access Journals (Sweden)

    Yu-Wei Wu

    2012-05-01

    Full Text Available Synaptic NMDA receptors (NMDARs are crucial for neural coding and plasticity. However, little is known about the adaptive function of extrasynaptic NMDARs occurring mainly on dendritic shafts. Here, we find that in CA1 pyramidal neurons, backpropagating action potentials (bAPs recruit shaft NMDARs exposed to ambient glutamate. In contrast, spine NMDARs are “protected,” under baseline conditions, from such glutamate influences by perisynaptic transporters: we detect bAP-evoked Ca2+ entry through these receptors upon local synaptic or photolytic glutamate release. During theta-burst firing, NMDAR-dependent Ca2+ entry either downregulates or upregulates an h-channel conductance (Gh of the cell depending on whether synaptic glutamate release is intact or blocked. Thus, the balance between activation of synaptic and extrasynaptic NMDARs can determine the sign of Gh plasticity. Gh plasticity in turn regulates dendritic input probed by local glutamate uncaging. These results uncover a metaplasticity mechanism potentially important for neural coding and memory formation.

  15. Distribution of vesicular glutamate transporters in the human brain

    Directory of Open Access Journals (Sweden)

    Erika eVigneault

    2015-03-01

    Full Text Available Glutamate is the major excitatory transmitter in the brain. Vesicular glutamate transporters (VGLUT1-3 are responsible for uploading glutamate into synaptic vesicles. VGLUT1 and VGLUT2 are considered as specific markers of canonical glutamatergic neurons, while VGLUT3 is found in neurons previously shown to use other neurotransmitters than glutamate. Although there exists a rich literature on the localization of these glutamatergic markers in the rodent brain, little is currently known about the distribution of VGLUT1-3 in the human brain. In the present study, using subtype specific probes and antisera, we examined the localization of the three vesicular glutamate transporters in the human brain by in situ hybridization, immunoautoradiography and immunohistochemistry. We found that the VGLUT1 transcript was highly expressed in the cerebral cortex, hippocampus and cerebellum, whereas VGLUT2 mRNA was mainly found in the thalamus and brainstem. VGLUT3 mRNA was localized in scarce neurons within the cerebral cortex, hippocampus, striatum and raphe nuclei. Following immunoautoradiographic labeling, intense VGLUT1- and VGLUT2-immunoreactivities were observed in all regions investigated (cerebral cortex, hippocampus, caudate-putamen, cerebellum, thalamus, amygdala, substantia nigra, raphe while VGLUT3 was absent from the thalamus and cerebellum. This extensive mapping of VGLUT1-3 in human brain reveals distributions that correspond for the most part to those previously described in rodent brains.

  16. Neuroprotective effects of the novel glutamate transporter inhibitor (-)-3-hydroxy-4,5,6,6a-tetrahydro-3aH-pyrrolo[3,4-d]-isoxazole-4-carboxylic acid, which preferentially inhibits reverse transport (glutamate release) compared with glutamate reuptake

    DEFF Research Database (Denmark)

    Colleoni, Simona; Jensen, Anders Asbjørn; Landucci, Elisa

    2008-01-01

    on the three hEAAT subtypes. (-)-HIP-A maintained the remarkable property, previously reported with the racemates, of inhibiting synaptosomal glutamate-induced [3H]D-aspartate release (reverse transport) at concentrations significantly lower than those inhibiting [3H]L-glutamate uptake. New data suggest...

  17. Relationship between Glutamate Dysfunction and Symptoms and Cognitive Function in Psychosis

    OpenAIRE

    Merritt, Kate; McGuire, Philip; Egerton, Alice

    2013-01-01

    The glutamate hypothesis of schizophrenia, proposed over two decades ago, originated following the observation that administration of drugs that block NMDA glutamate receptors, such as ketamine, could induce schizophrenia-like symptoms. Since then, this hypothesis has been extended to describe how glutamate abnormalities may disturb brain function and underpin psychotic symptoms and cognitive impairments. The glutamatergic system is now a major focus for the development of new compounds in sc...

  18. Agmatine Prevents Adaptation of the Hippocampal Glutamate System in Chronic Morphine-Treated Rats.

    Science.gov (United States)

    Wang, Xiao-Fei; Zhao, Tai-Yun; Su, Rui-Bin; Wu, Ning; Li, Jin

    2016-12-01

    Chronic exposure to opioids induces adaptation of glutamate neurotransmission, which plays a crucial role in addiction. Our previous studies revealed that agmatine attenuates opioid addiction and prevents the adaptation of glutamate neurotransmission in the nucleus accumbens of chronic morphine-treated rats. The hippocampus is important for drug addiction; however, whether adaptation of glutamate neurotransmission is modulated by agmatine in the hippocampus remains unknown. Here, we found that continuous pretreatment of rats with ascending doses of morphine for 5 days resulted in an increase in the hippocampal extracellular glutamate level induced by naloxone (2 mg/kg, i.p.) precipitation. Agmatine (20 mg/kg, s.c.) administered concurrently with morphine for 5 days attenuated the elevation of extracellular glutamate levels induced by naloxone precipitation. Furthermore, in the hippocampal synaptosome model, agmatine decreased the release and increased the uptake of glutamate in synaptosomes from chronic morphine-treated rats, which might contribute to the reduced elevation of glutamate levels induced by agmatine. We also found that expression of the hippocampal NR2B subunit, rather than the NR1 subunit, of N-methyl-D-aspartate receptors (NMDARs) was down-regulated after chronic morphine treatment, and agmatine inhibited this reduction. Taken together, agmatine prevented the adaptation of the hippocampal glutamate system caused by chronic exposure to morphine, including modulating extracellular glutamate concentration and NMDAR expression, which might be one of the mechanisms underlying the attenuation of opioid addiction by agmatine.

  19. Elucidation of the pathways of catabolic glutamate conversion in three thermophilic anaerobic bacteria.

    Science.gov (United States)

    Plugge, C M; van Leeuwen, J M; Hummelen, T; Balk, M; Stams, A J

    2001-07-01

    The glutamate catabolism of three thermophilic syntrophic anaerobes was compared based on the combined use of [(13)C] glutamate NMR measurements and enzyme activity determinations. In some cases the uptake of intermediates from different pathways was studied. The three organisms, Caloramator coolhaasii, Thermanaerovibrio acidaminovorans and strain TGO, had a different stoichiometry of glutamate conversion and were dependent on the presence of a hydrogen scavenger (Methanobacterium thermoautotrophicum Z245) to a different degree for their growth. C. coolhaasii formed acetate, CO(2), NH(4)(+) and H(2) from glutamate. Acetate was found to be formed through the beta-methylaspartate pathway in pure culture as well as in coculture. T. acidaminovorans converted glutamate to acetate, propionate, CO(2), NH(4)(+) and H(2). Most likely, this organism uses the beta-methylaspartate pathway for acetate formation. Propionate formation occurred through a direct oxidation of glutamate via succinyl-CoA and methylmalonyl-CoA. The metabolism of T. acidaminovorans shifted in favour of propionate formation when grown in coculture with the methanogen, but this did not lead to the use of a different glutamate degradation pathway. Strain TGO, an obligate syntrophic glutamate-degrading organism, formed propionate, traces of succinate, CO(2), NH(4)(+) and H(2). Glutamate was converted to propionate oxidatively via the intermediates succinyl-CoA and methylmalonyl-CoA. A minor part of the succinyl-CoA was converted to succinate and excreted.

  20. Effects of Bee Venom on Glutamate-Induced Toxicity in Neuronal and Glial Cells

    Directory of Open Access Journals (Sweden)

    Sang Min Lee

    2012-01-01

    Full Text Available Bee venom (BV, which is extracted from honeybees, is used in traditional Korean medical therapy. Several groups have demonstrated the anti-inflammatory effects of BV in osteoarthritis both in vivo and in vitro. Glutamate is the predominant excitatory neurotransmitter in the central nervous system (CNS. Changes in glutamate release and uptake due to alterations in the activity of glutamate transporters have been reported in many neurodegenerative diseases, including Parkinson's disease, Alzheimer's disease, and amyotrophic lateral sclerosis. To assess if BV can prevent glutamate-mediated neurotoxicity, we examined cell viability and signal transduction in glutamate-treated neuronal and microglial cells in the presence and absence of BV. We induced glutamatergic toxicity in neuronal cells and microglial cells and found that BV protected against cell death. Furthermore, BV significantly inhibited the cellular toxicity of glutamate, and pretreatment with BV altered MAP kinase activation (e.g., JNK, ERK, and p38 following exposure to glutamate. These findings suggest that treatment with BV may be helpful in reducing glutamatergic cell toxicity in neurodegenerative diseases.

  1. VGLUTs and Glutamate Synthesis—Focus on DRG Neurons and Pain

    Directory of Open Access Journals (Sweden)

    Mariana Malet

    2015-12-01

    Full Text Available The amino acid glutamate is the principal excitatory transmitter in the nervous system, including in sensory neurons that convey pain sensation from the periphery to the brain. It is now well established that a family of membrane proteins, termed vesicular glutamate transporters (VGLUTs, serve a critical function in these neurons: they incorporate glutamate into synaptic vesicles. VGLUTs have a central role both under normal neurotransmission and pathological conditions, such as neuropathic or inflammatory pain. In the present short review, we will address VGLUTs in the context of primary afferent neurons. We will focus on the role of VGLUTs in pain triggered by noxious stimuli, peripheral nerve injury, and tissue inflammation, as mostly explored in transgenic mice. The possible interplay between glutamate biosynthesis and VGLUT-dependent packaging in synaptic vesicles, and its potential impact in various pain states will be presented.

  2. Limited energy supply in Müller cells alters glutamate uptake

    DEFF Research Database (Denmark)

    Toft-Kehler, Anne Katrine; Skytt, Dorte Marie; Poulsen, Kristian Arild

    2014-01-01

    The viability of retinal ganglion cells (RGC) is essential for the maintenance of visual function. RGC homeostasis is maintained by the surrounding retinal glial cells, the Müller cells, which buffer the extracellular concentration of neurotransmitters and provide the RGCs with energy. This study...... evaluates if glucose-deprivation of Müller cells interferes with their ability to remove glutamate from the extracellular space. The human Müller glial cell line, Moorfields/Institute of Ophthalmology-Müller 1, was used to study changes in glutamate uptake. Excitatory amino acid transporter (EAAT) proteins...... were up-regulated in glucose-deprived Müller cells and glutamate uptake was significantly increased in the absence of glucose. The present findings revealed an up-regulation of EAAT1 and EAAT2 in glucose-deprived Müller cells as well as an increased ability to take up glutamate. Hence, glucose...

  3. probing the cob(ii)alamin conductor hypothesis with glutamate ...

    African Journals Online (AJOL)

    dell

    Glutamate mutase activity was also demonstrated upon incubation of GlmS and E with 3',5'- ... overproduced in E.coli (Huhta et al. 2001,. Huhta et ..... Biochemistry. 37: 9704-9715. Buckel W 2001 Unusual enzymes involved in five pathways of glutamate fermentation. Appl. Microbiol. Biotechnol. 57: 263-273. Buckel W and ...

  4. Electrogenic glutamate uptake is a major current carrier in the membrane of axolotl retinal glial cells

    Science.gov (United States)

    Brew, Helen; Attwell, David

    1987-06-01

    Glutamate is taken up avidly by glial cells in the central nervous system1. Glutamate uptake may terminate the transmitter action of glutamate released from neurons1, and keep extracellular glutamate at concentrations below those which are neurotoxic. We report here that glutamate evokes a large inward current in retinal glial cells which have their membrane potential and intracellular ion concentrations controlled by the whole-cell patch-clamp technique2. This current seems to be due to an electrogenic glutamate uptake carrier, which transports at least two sodium ions with every glutamate anion carried into the cell. Glutamate uptake is strongly voltage-dependent, decreasing at depolarized potentials: when fully activated, it contributes almost half of the conductance in the part of the glial cell membrane facing the retinal neurons. The spatial localization, glutamate affinity and magnitude of the uptake are appropriate for terminating the synaptic action of glutamate released from photoreceptors and bipolar cells. These data challenge present explanations of how the b-wave of the electroretinogram is generated, and suggest a mechanism for non-vesicular voltage-dependent release of glutamate from neurons.

  5. Exogenous glutamate induces short and long-term potentiation in the rat medial vestibular nuclei.

    Science.gov (United States)

    Grassi, S; Frondaroli, A; Pessia, M; Pettorossi, V E

    2001-08-08

    In rat brain stem slices, high concentrations of exogenous glutamate induce long-term potentiation (LTP) of the field potentials evoked in the medial vestibular nuclei (MVN) by vestibular afferent stimulation. At low concentrations, glutamate can also induce short-term potentiation (STP), indicating that LTP and STP are separate events depending on the level of glutamatergic synapse activation. LTP and STP are prevented by blocking NMDA receptors and nitric oxide (NO) synthesis. Conversely, blocking platelet-activating factor (PAF) and group I metabotropic glutamate receptors only prevents the full development of LTP. Moreover, in the presence of blocking agents, glutamate causes transient inhibition, suggesting that when potentiation is impeded, exogenous glutamate can activate presynaptic mechanisms that reduce glutamate release.

  6. Immunocytochemical localization of the glutamate transporter GLT-1 in goldfish (Carassius auratus) retina

    NARCIS (Netherlands)

    Vandenbranden, C. A.; Yazulla, S.; Studholme, K. M.; Kamphuis, W.; Kamermans, M.

    2000-01-01

    Glutamate is the major excitatory neurotransmitter in the retina of vertebrates. Electrophysiological experiments in goldfish and salamander have shown that neuronal glutamate transporters play an important role in the clearance of glutamate from cone synaptic clefts. In this study, the localization

  7. [Molecular organization of glutamate-sensitive chemoexcitatory membranes of nerve cells. Comparative analysis of glutamate-binding membrane proteins from the cerebral cortex of rats and humans].

    Science.gov (United States)

    Dambinova, S A; Gorodinskiĭ, A I; Lekomtseva, T M; Koreshonkov, O N

    1987-10-01

    The kinetics of 3H-L-glutamate binding to human brain synaptic membranes revealed the existence of one type of binding sites with Kd and Vmax comparable with those for freshly isolated rat brain membranes. The fraction of glutamate-binding proteins (GBP) was shown to contain three components with Mr of 14, 60 and 280 kD whose stoichiometry is specific for human and rat brain. All fractions were found to bind the radiolabeled neurotransmitter and to dissociate into subunits with Mr of 14 kD after treatment with-potent detergents (with the exception of the 56-60 kD component). Study of association-dissociation of GBP protein subunits by high performance liquid chromatography confirmed the hypothesis on the oligomeric structure of glutamate receptors which are made up of low molecular weight glycoprotein-lipid subunits and which form ionic channels by way of repeated association. Despite the similarity of antigen determinants in the active center of glutamate receptors from human and rat brain, it was assumed that the stoichiometry of structural organization of receptor subunits isolated from different sources is different. The functional role of structural complexity of human brain glutamate receptors is discussed.

  8. Glutamic Acid Residues in HIV-1 p6 Regulate Virus Budding and Membrane Association of Gag.

    Science.gov (United States)

    Friedrich, Melanie; Setz, Christian; Hahn, Friedrich; Matthaei, Alina; Fraedrich, Kirsten; Rauch, Pia; Henklein, Petra; Traxdorf, Maximilian; Fossen, Torgils; Schubert, Ulrich

    2016-04-25

    The HIV-1 Gag p6 protein regulates the final abscission step of nascent virions from the cell membrane by the action of its two late (L-) domains, which recruit Tsg101 and ALIX, components of the ESCRT system. Even though p6 consists of only 52 amino acids, it is encoded by one of the most polymorphic regions of the HIV-1 gag gene and undergoes various posttranslational modifications including sumoylation, ubiquitination, and phosphorylation. In addition, it mediates the incorporation of the HIV-1 accessory protein Vpr into budding virions. Despite its small size, p6 exhibits an unusually high charge density. In this study, we show that mutation of the conserved glutamic acids within p6 increases the membrane association of Pr55 Gag followed by enhanced polyubiquitination and MHC-I antigen presentation of Gag-derived epitopes, possibly due to prolonged exposure to membrane bound E3 ligases. The replication capacity of the total glutamic acid mutant E0A was almost completely impaired, which was accompanied by defective virus release that could not be rescued by ALIX overexpression. Altogether, our data indicate that the glutamic acids within p6 contribute to the late steps of viral replication and may contribute to the interaction of Gag with the plasma membrane.

  9. Synaptic glutamate spillover increases NMDA receptor reliability at the cerebellar glomerulus

    OpenAIRE

    Mitchell, Cassie S.; Lee, Robert H.

    2011-01-01

    Glutamate spillover in the mossy fiber to granule cell cerebellar glomeruli has been hypothesized to increase neurotransmission reliability. In this study, we evaluate this hypothesis using an experimentally-based quantitative model of glutamate spillover on the N-methyl-d-aspartate receptors (NMDA-Rs) at the cerebellar glomerulus. The transient and steady-state responses of NMDA-Rs were examined over a physiological range of firing rates. Examined cases included direct glutamate release acti...

  10. Binding of L-glutamic acid to non-receptor materials

    International Nuclear Information System (INIS)

    Periyasamy, S.; Ito, M.; Chiu, T.H.

    1986-01-01

    [ 3 H]L-glutamic acid ([ 3 H]Glu) binding to microfuge tubes, glass fiber filters, and glass tubes was studied in 4 buffers (50 mM, pH 7.4 at 4 0 C). Binding assays were done at 0-4 0 C. Binding to these materials was negligible in the absence of external force, but was increased by suction or centrifugation in Tris-HCl or Tris-citrate buffer. The force-induced binding was much less or was eliminated in Tris-acetate or HEPES-KOH buffer. [ 3 H]Glu binding to microfuge tubes was inhibited by L- but not D- isomers of glutamate and aspartate. DL-2-amino-7-phosphonoheptanoic acid was without effect. Other compounds that showed low to moderate inhibitory activity were N-methyl-D-aspartate, quisqualate, L-glutamic acid diethyl ester. N-methyl-L-aspartate, kainate, and 2-amino-4-phosphonobutyrate. Binding was inhibited by denatured P 2 membrane preparation in Tris-acetate buffer was used. It is suggested that Tris-acetate or HEPES-KOH buffer should be used in the glutamate binding assay

  11. Swimming pools and intra-city climates: Influences on residential ...

    African Journals Online (AJOL)

    While determinants such as household income, regional climate, water price, property size and household occupancy have been comprehensively studied and modelled, other determinants such as swimming pools and intra-city climates have not. This study examines residential water consumption in the City of Cape Town ...

  12. Synthesis of edatrexate (2-13C-glutamate)

    International Nuclear Information System (INIS)

    DeGraw, J.I.; Colwell, W.T.; Jue, Thomas

    1997-01-01

    The experimental antitumor drug Edatrexate, labeled with 99% 13 C at the 2-position of the glutamate acid group was required for 13 C-magnetic resonance spectroscopy studies in biological media. Coupling of 2,4-diamino-4-deoxy-10-ethyl-10-deazapteroic acid with diethyl L-2- 13 C-glutamate as promoted by BOP reagent afforded Edatrexate (2- 13 C-glu) diethyl ester in 60% yield following purification by column chromatography. Saponification by aqueous NaOH in 2-methoxyethanol gave the target molecule in 44% yield or 26% overall. (author)

  13. Conformational Studies on γ - Benzyl- L- Glutamate and L- Valine Containing Block Copolypeptides

    OpenAIRE

    Kumar, Ajay

    2010-01-01

    Conformational studies on γ - benzyl-L- glutamate and L- valine containing block copolypeptides are reported using IR and CD spectra. The block copolypeptides contain valine block in the center and on both sides of the valine are γ - benzyl- L- glutamate blocks. The changes in conformation with increase in chain length of γ - benzyl- L- glutamate blocks are observed. When the chain length of γ - benzyl-L- glutamate block is 13, the block copolypeptide crystallized into beta conformation. With...

  14. Evidence for a role of glutamate as an efferent transmitter in taste buds

    Directory of Open Access Journals (Sweden)

    Anderson Catherine B

    2010-06-01

    Full Text Available Abstract Background Glutamate has been proposed as a transmitter in the peripheral taste system in addition to its well-documented role as an umami taste stimulus. Evidence for a role as a transmitter includes the presence of ionotropic glutamate receptors in nerve fibers and taste cells, as well as the expression of the glutamate transporter GLAST in Type I taste cells. However, the source and targets of glutamate in lingual tissue are unclear. In the present study, we used molecular, physiological and immunohistochemical methods to investigate the origin of glutamate as well as the targeted receptors in taste buds. Results Using molecular and immunohistochemical techniques, we show that the vesicular transporters for glutamate, VGLUT 1 and 2, but not VGLUT3, are expressed in the nerve fibers surrounding taste buds but likely not in taste cells themselves. Further, we show that P2X2, a specific marker for gustatory but not trigeminal fibers, co-localizes with VGLUT2, suggesting the VGLUT-expressing nerve fibers are of gustatory origin. Calcium imaging indicates that GAD67-GFP Type III taste cells, but not T1R3-GFP Type II cells, respond to glutamate at concentrations expected for a glutamate transmitter, and further, that these responses are partially blocked by NBQX, a specific AMPA/Kainate receptor antagonist. RT-PCR and immunohistochemistry confirm the presence of the Kainate receptor GluR7 in Type III taste cells, suggesting it may be a target of glutamate released from gustatory nerve fibers. Conclusions Taken together, the results suggest that glutamate may be released from gustatory nerve fibers using a vesicular mechanism to modulate Type III taste cells via GluR7.

  15. Therapeutic effects of glutamic acid in piglets challenged with deoxynivalenol.

    Science.gov (United States)

    Wu, Miaomiao; Xiao, Hao; Ren, Wenkai; Yin, Jie; Tan, Bie; Liu, Gang; Li, Lili; Nyachoti, Charles Martin; Xiong, Xia; Wu, Guoyao

    2014-01-01

    The mycotoxin deoxynivalenol (DON), one of the most common food contaminants, primarily targets the gastrointestinal tract to affect animal and human health. This study was conducted to examine the protective function of glutamic acid on intestinal injury and oxidative stress caused by DON in piglets. Twenty-eight piglets were assigned randomly into 4 dietary treatments (7 pigs/treatment): 1) uncontaminated control diet (NC), 2) NC+DON at 4 mg/kg (DON), 3) NC+2% glutamic acid (GLU), and 4) NC+2% glutamic acid + DON at 4 mg/kg (DG). At day 15, 30 and 37, blood samples were collected to determine serum concentrations of CAT (catalase), T-AOC (total antioxidant capacity), H2O2 (hydrogen peroxide), NO (nitric oxide), MDA (maleic dialdehyde), DAO (diamine oxidase) and D-lactate. Intestinal morphology, and the activation of Akt/mTOR/4EBP1 signal pathway, as well as the concentrations of H2O2, MDA, and DAO in kidney, liver and small intestine, were analyzed at day 37. Results showed that DON significantly (Pglutamic acid supplementation according to the change of oxidative parameters in blood and tissues. Meanwhile, DON caused obvious intestinal injury from microscopic observations and permeability indicators, which was alleviated by glutamic acid supplementation. Moreover, the inhibition of DON on Akt/mTOR/4EBP1 signal pathway was reduced by glutamic acid supplementation. Collectively, these data suggest that glutamic acid may be a useful nutritional regulator for DON-induced damage manifested as oxidative stress, intestinal injury and signaling inhibition.

  16. Exciting Pools

    Science.gov (United States)

    Wright, Bradford L.

    1975-01-01

    Advocates the creation of swimming pool oscillations as part of a general investigation of mechanical oscillations. Presents the equations, procedure for deriving the slosh modes, and methods of period estimation for exciting swimming pool oscillations. (GS)

  17. Frontal glutamate and reward processing in adolescence and adulthood.

    Science.gov (United States)

    Gleich, Tobias; Lorenz, Robert C; Pöhland, Lydia; Raufelder, Diana; Deserno, Lorenz; Beck, Anne; Heinz, Andreas; Kühn, Simone; Gallinat, Jürgen

    2015-11-01

    The fronto-limbic network interaction, driven by glutamatergic and dopaminergic neurotransmission, represents a core mechanism of motivated behavior and personality traits. Reward seeking behavior undergoes tremendous changes in adolescence paralleled by neurobiological changes of this network including the prefrontal cortex, striatum and amygdala. Since fronto-limbic dysfunctions also underlie major psychiatric diseases beginning in adolescence, this investigation focuses on network characteristics separating adolescents from adults. To investigate differences in network interactions, the brain reward system activity (slot machine task) together with frontal glutamate concentration (anterior cingulate cortex, ACC) was measured in 28 adolescents and 26 adults employing functional magnetic resonance imaging and magnetic resonance spectroscopy, respectively. An inverse coupling of glutamate concentrations in the ACC and activation of the ventral striatum was observed in adolescents. Further, amygdala response in adolescents was negatively correlated with the personality trait impulsivity. For adults, no significant associations of network components or correlations with impulsivity were found. The inverse association between frontal glutamate concentration and striatal activation in adolescents is in line with the triadic model of motivated behavior stressing the important role of frontal top-down inhibition on limbic structures. Our data identified glutamate as the mediating neurotransmitter of this inhibitory process and demonstrates the relevance of glutamate on the reward system and related behavioral traits like impulsivity. This fronto-limbic coupling may represent a vulnerability factor for psychiatric disorders starting in adolescence but not in adulthood.

  18. Coupled ion binding and structural transitions along the transport cycle of glutamate transporters

    OpenAIRE

    Verdon, Grégory; Oh, SeCheol; Serio, Ryan N; Boudker, Olga

    2014-01-01

    eLife digest Molecules of glutamate can carry messages between cells in the brain, and these signals are essential for thought and memory. Glutamate molecules can also act as signals to build new connections between brain cells and to prune away unnecessary ones. However, too much glutamate outside of the cells kills the brain tissue and can lead to devastating brain diseases. In a healthy brain, special pumps called glutamate transporters move these molecules back into the brain cells, where...

  19. Glutamate abnormalities in obsessive compulsive disorder: neurobiology, pathophysiology, and treatment.

    Science.gov (United States)

    Pittenger, Christopher; Bloch, Michael H; Williams, Kyle

    2011-12-01

    Obsessive compulsive disorder is prevalent, disabling, incompletely understood, and often resistant to current therapies. Established treatments consist of specialized cognitive-behavioral psychotherapy and pharmacotherapy with medications targeting serotonergic and dopaminergic neurotransmission. However, remission is rare, and more than a quarter of OCD sufferers receive little or no benefit from these approaches, even when they are optimally delivered. New insights into the disorder, and new treatment strategies, are urgently needed. Recent evidence suggests that the ubiquitous excitatory neurotransmitter glutamate is dysregulated in OCD, and that this dysregulation may contribute to the pathophysiology of the disorder. Here we review the current state of this evidence, including neuroimaging studies, genetics, neurochemical investigations, and insights from animal models. Finally, we review recent findings from small clinical trials of glutamate-modulating medications in treatment-refractory OCD. The precise role of glutamate dysregulation in OCD remains unclear, and we lack blinded, well-controlled studies demonstrating therapeutic benefit from glutamate-modulating agents. Nevertheless, the evidence supporting some important perturbation of glutamate in the disorder is increasingly strong. This new perspective on the pathophysiology of OCD, which complements the older focus on monoaminergic neurotransmission, constitutes an important focus of current research and a promising area for the ongoing development of new therapeutics. Copyright © 2011 Elsevier Inc. All rights reserved.

  20. Removal of lead from aqueous solution on glutamate intercalated layered double hydroxide

    Directory of Open Access Journals (Sweden)

    Shen Yanming

    2017-05-01

    Full Text Available Glutamate intercalated Mg–Al layered double hydroxide (LDH was prepared by co-precipitation and the removal of Pb2+ in the aqueous solution was investigated. The prepared samples were characterized by XRD, FT-IR and SEM. It was shown that glutamate can intercalate into the interlayer space of Mg–Al LDH. The glutamate intercalated Mg–Al LDH can effectively adsorb Pb2+ in the aqueous solution with an adsorption capacity of 68.49 mg g−1. The adsorption of Pb2+ on glutamate intercalated Mg–Al LDH fitted the pseudo-second-order kinetics model and the isotherm can be well defined by Langmuir model.

  1. Brain microdialysis of GABA and glutamate : What does it signify?

    NARCIS (Netherlands)

    Timmerman, W; Westerink, B.H.C.

    1997-01-01

    Microdialysis has become a frequently used method to study extracellular levels of GABA and glutamate in the central nervous system. However, the fact that the major part of GABA and glutamate as measured by microdialysis does not fulfill the classical criteria for exocytotic release questions the

  2. Glutamic Acid Selective Chemical Cleavage of Peptide Bonds.

    Science.gov (United States)

    Nalbone, Joseph M; Lahankar, Neelam; Buissereth, Lyssa; Raj, Monika

    2016-03-04

    Site-specific hydrolysis of peptide bonds at glutamic acid under neutral aqueous conditions is reported. The method relies on the activation of the backbone amide chain at glutamic acid by the formation of a pyroglutamyl (pGlu) imide moiety. This activation increases the susceptibility of a peptide bond toward hydrolysis. The method is highly specific and demonstrates broad substrate scope including cleavage of various bioactive peptides with unnatural amino acid residues, which are unsuitable substrates for enzymatic hydrolysis.

  3. Hydrodynamics of AHWR gravity driven water pool under simulated LOCA conditions

    International Nuclear Information System (INIS)

    Thangamani, I.; Verma, Vishnu; Ali, Seik Mansoor

    2015-01-01

    The Advanced Heavy Water Reactor (AHWR) employs a double containment concept with a large inventory of water within the Gravity Driven Water Pool (GDWP) located at a high elevation within the primary containment building. GDWP performs several important safety functions in a passive manner, and hence it is essential to understand the hydrodynamics that this pool will be subjected to in case of an accident such as LOCA. In this paper, a detailed thermal hydraulic analysis for AHWR containment transients is presented for postulated LOCA scenarios involving RIH break sizes ranging from 2% to 50%. The analysis is carried out using in-house containment thermal hydraulics code 'CONTRAN'. The blowdown mass and energy discharge data for each break size, along with the geometrical details of the AHWR containment forms the main input for the analysis. Apart from obtaining the pressure and temperature transients within the containment building, the focus of this work is on simulating the hydrodynamic phenomena of vent clearing and pool swell occurring in the GDWP. The variation of several key parameters such as primary containment V1 and V2 volume pressure, temperature and V1-V2 differential pressure with time, BOP rupture time, vent clearing velocity, effect of pool swell on the V2 air-space pressure, GDWP water level etc. are discussed in detail and important findings are highlighted. Further, the effect of neglecting the pool swell phenomenon on the containment transients is also clearly brought out by a comparative study. The numerical studies presented in this paper give insight into containment transients that would be useful to both the system designer as well as the regulator. (author)

  4. Vesicular glutamate release from central axons contributes to myelin damage.

    Science.gov (United States)

    Doyle, Sean; Hansen, Daniel Bloch; Vella, Jasmine; Bond, Peter; Harper, Glenn; Zammit, Christian; Valentino, Mario; Fern, Robert

    2018-03-12

    The axon myelin sheath is prone to injury associated with N-methyl-D-aspartate (NMDA)-type glutamate receptor activation but the source of glutamate in this context is unknown. Myelin damage results in permanent action potential loss and severe functional deficit in the white matter of the CNS, for example in ischemic stroke. Here, we show that in rats and mice, ischemic conditions trigger activation of myelinic NMDA receptors incorporating GluN2C/D subunits following release of axonal vesicular glutamate into the peri-axonal space under the myelin sheath. Glial sources of glutamate such as reverse transport did not contribute significantly to this phenomenon. We demonstrate selective myelin uptake and retention of a GluN2C/D NMDA receptor negative allosteric modulator that shields myelin from ischemic injury. The findings potentially support a rational approach toward a low-impact prophylactic therapy to protect patients at risk of stroke and other forms of excitotoxic injury.

  5. Immune labeling and purification of a 71-kDa glutamate-binding protein from brain synaptic membranes

    International Nuclear Information System (INIS)

    Chen, J.W.; Cunningham, M.D.; Galton, N.; Michaelis, E.K.

    1988-01-01

    Immunoblot studies of synaptic membranes isolated from rat brain using antibodies raised against a previously purified glutamate-binding protein (GBP) indicated labeling of an ∼ 70-kDa protein band. Since the antibodies used were raised against a 14-kDa GBP, the present studies were undertaken to explore the possibility that the 14-kDa protein may have been a proteolytic fragment of a larger M/sub r/ protein in synaptic membranes. The major protein enriched in the most highly purified fractions was a 71-kDa glycoprotein, but a 63-kDa protein was co-purified during most steps of the isolation procedure. The glutamate-binding characteristics of these isolated protein fractions were very similar to those previously described for the 14-kDa GBP, including estimated dissociation constants for L-glutamate binding of 0.25 and 1 + M, inhibition of glutamate binding by azide and cyanide, and a selectivity of the ligand binding site for L-glutamate and L-aspartate. The neuroexcitatory analogs of L-glutamate and L-aspartate, ibotenate, quisqualate, and D-glutamate, inhibited L[ 3 H]glutamate binding to the isolated proteins, as did the antagonist of L-glutamate-induced neuronal excitation, L-glutamate diethylester. On the basis of the lack of any detectable glutamate-related enzyme activity associated with the isolated proteins and the presence of distinguishing sensitivities to analogs that inhibit glutamate transport carriers in synaptic membranes, it is proposed that the 71-kDa protein may be a component of a physiologic glutamate receptor complex in neuronal membranes

  6. Glutamate and GABA in vestibulo-sympathetic pathway neurons

    Directory of Open Access Journals (Sweden)

    Gay R Holstein

    2016-02-01

    Full Text Available The vestibulo-sympathetic reflex actively modulates blood pressure during changes in posture. This reflex allows humans to stand up and quadrupeds to rear or climb without a precipitous decline in cerebral perfusion. The vestibulo-sympathetic reflex pathway conveys signals from the vestibular end organs to the caudal vestibular nuclei. These cells, in turn, project to pre-sympathetic neurons in the rostral and caudal ventrolateral medulla (RVLM and CVLM, respectively. The present study assessed glutamate- and GABA-related immunofluorescence associated with central vestibular neurons of the vestibulo-sympathetic reflex pathway in rats. Retrograde FluoroGold tract tracing was used to label vestibular neurons with projections to RVLM or CVLM, and sinusoidal galvanic vestibular stimulation was employed to activate these pathways. Central vestibular neurons of the vestibulo-sympathetic reflex were identified by co-localization of FluoroGold and cFos protein, which accumulates in some vestibular neurons following galvanic stimulation. Triple-label immunofluorescence was used to co-localize glutamate- or GABA- labeling in the identified vestibulo-sympathetic reflex pathway neurons. Most activated projection neurons displayed intense glutamate immunofluorescence, suggestive of glutamatergic neurotransmission. To support this, anterograde tracer was injected into the caudal vestibular nuclei. Vestibular axons and terminals in RVLM and CVLM co-localized the anterograde tracer and vesicular glutamate transporter-2 signals. Other retrogradely-labeled cFos-positive neurons displayed intense GABA immunofluorescence. Vestibulo-sympathetic reflex pathway neurons of both phenotypes were present in the caudal medial and spinal vestibular nuclei, and projected to both RVLM and CVLM. As a group, however, triple-labeled vestibular cells with intense glutamate immunofluorescence were located more rostrally in the vestibular nuclei than the GABAergic neurons. Only the

  7. 21 CFR 573.500 - Condensed, extracted glutamic acid fermentation product.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Condensed, extracted glutamic acid fermentation product. 573.500 Section 573.500 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... fermentation product. Condensed, extracted glutamic acid fermentation product may be safely used in animal feed...

  8. Palmitoylethanolamide Inhibits Glutamate Release in Rat Cerebrocortical Nerve Terminals

    Directory of Open Access Journals (Sweden)

    Tzu-Yu Lin

    2015-03-01

    Full Text Available The effect of palmitoylethanolamide (PEA, an endogenous fatty acid amide displaying neuroprotective actions, on glutamate release from rat cerebrocortical nerve terminals (synaptosomes was investigated. PEA inhibited the Ca2+-dependent release of glutamate, which was triggered by exposing synaptosomes to the potassium channel blocker 4-aminopyridine. This release inhibition was concentration dependent, associated with a reduction in cytosolic Ca2+ concentration, and not due to a change in synaptosomal membrane potential. The glutamate release-inhibiting effect of PEA was prevented by the Cav2.1 (P/Q-type channel blocker ω-agatoxin IVA or the protein kinase A inhibitor H89, not affected by the intracellular Ca2+ release inhibitors dantrolene and CGP37157, and partially antagonized by the cannabinoid CB1 receptor antagonist AM281. Based on these results, we suggest that PEA exerts its presynaptic inhibition, likely through a reduction in the Ca2+ influx mediated by Cav2.1 (P/Q-type channels, thereby inhibiting the release of glutamate from rat cortical nerve terminals. This release inhibition might be linked to the activation of presynaptic cannabinoid CB1 receptors and the suppression of the protein kinase A pathway.

  9. Inhibitory mechanism of l-glutamic acid on spawning of the starfish Patiria (Asterina) pectinifera.

    Science.gov (United States)

    Mita, Masatoshi

    2017-03-01

    l-Glutamic acid was previously identified as an inhibitor of spawning in the starfish Patiria (Asterina) pectinifera; this study examined how l-glutamic acid works. Oocyte release from ovaries of P. pectinifera occurred after germinal vesicle breakdown (GVBD) and follicular envelope breakdown (FEBD) when gonads were incubated ex vivo with either relaxin-like gonad-stimulating peptide (RGP) or 1-methyladenine (1-MeAde). l-Glutamic acid blocked this spawning phenotype, causing the mature oocytes to remain within the ovaries. Neither RGP-induced 1-MeAde production in ovarian follicle cells nor 1-MeAde-induced GVBD and FEBD was affected by l-glutamic acid. l-Glutamic acid may act through metabotropic receptors in the ovaries to inhibit spawning, as l-(+)-2-amino-4-phosphonobutyric acid, an agonist for metabotropic glutamate receptors, also inhibited spawning induced by 1-MeAde. Application of acetylcholine (ACH) to ovaries under inhibitory conditions with l-glutamic acid, however, brought about spawning, possibly by inducing contraction of the ovarian wall to discharge mature oocytes from the ovaries concurrently with GVBD and FEBD. Thus, l-glutamic acid may inhibit ACH secretion from gonadal nerve cells in the ovary. Mol. Reprod. Dev. 84: 246-256, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  10. Glutamic Acid as Enhancer of Protein Synthesis Kinetics in Hepatocytes from Old Rats.

    Science.gov (United States)

    Brodsky, V Y; Malchenko, L A; Butorina, N N; Lazarev Konchenko, D S; Zvezdina, N D; Dubovaya, T K

    2017-08-01

    Dense cultures of hepatocytes from old rats (~2 years old, body weight 530-610 g) are different from similar cultures of hepatocytes from young rats by the low amplitude of protein synthesis rhythm. Addition of glutamic acid (0.2, 0.4, or 0.6 mg/ml) into the culture medium with hepatocytes of old rats resulted in increase in the oscillation amplitudes of the protein synthesis rhythm to the level of young rats. A similar action of glutamic acid on the protein synthesis kinetics was observed in vivo after feeding old rats with glutamic acid. Inhibition of metabotropic receptors of glutamic acid with α-methyl-4-carboxyphenylglycine (0.01 mg/ml) abolished the effect of glutamic acid. The amplitude of oscillation of the protein synthesis rhythm in a cell population characterizes synchronization of individual oscillations caused by direct cell-cell communications. Hence, glutamic acid, acting as a receptor-dependent transmitter, enhanced direct cell-cell communications of hepatocytes that were decreased with aging. As differentiated from other known membrane signaling factors (gangliosides, norepinephrine, serotonin, dopamine), glutamic acid can penetrate into the brain and thus influence the communications and protein synthesis kinetics that are disturbed with aging not only in hepatocytes, but also in neurons.

  11. Genetic and metabolic engineering for microbial production of poly-γ-glutamic acid.

    Science.gov (United States)

    Cao, Mingfeng; Feng, Jun; Sirisansaneeyakul, Sarote; Song, Cunjiang; Chisti, Yusuf

    2018-05-28

    Poly-γ-glutamic acid (γ-PGA) is a natural biopolymer of glutamic acid. The repeating units of γ-PGA may be derived exclusively from d-glutamic acid, or l-glutamic acid, or both. The monomer units are linked by amide bonds between the α-amino group and the γ-carboxylic acid group. γ-PGA is biodegradable, edible and water-soluble. It has numerous existing and emerging applications in processing of foods, medicines and cosmetics. This review focuses on microbial production of γ-PGA via genetically and metabolically engineered recombinant bacteria. Strategies for improving production of γ-PGA include modification of its biosynthesis pathway, enhancing the production of its precursor (glutamic acid), and preventing loss of the precursor to competing byproducts. These and other strategies are discussed. Heterologous synthesis of γ-PGA in industrial bacterial hosts that do not naturally produce γ-PGA is discussed. Emerging trends and the challenges affecting the production of γ-PGA are reviewed. Copyright © 2018. Published by Elsevier Inc.

  12. N-13 L-glutamate uptake in malignancy: its relationship to blood flow

    International Nuclear Information System (INIS)

    Knapp, W.H.; Helus, F.; Sinn, H.; Ostertag, H.; Georgi, P.; Brandeis, W.E.; Braun, A.

    1984-01-01

    Studies on glutamate uptake, with special reference to perfusion, were carried out in 35 rats, each bearing one of five different tumor transplants; also in 15 rats after bone fracture, and in three rabbits. Single-pass extraction of N-13 glutamate was 85-93% in the VX2 tumor of the rabbit and in muscle. Bone fracture in rats caused a threefold increase of tracer uptake 2 days after the event. Comparing N-13 glutamate uptake with the retention of 1-121 microspheres, identical tumor-to-muscle ratios were found for three out of five tumor lines. Comparing the uptake with that of C-11 butanol (ten rats), a close correlation was observed throughout the range of tumor lines. The results suggested that glutamate uptake by malignant tumors is related to blood flow. In nine patients with malignant or benign lesions tumor-to-muscle uptake of N-13 glutamate and Tl-201 showed a linear correlation close to identity

  13. Swimming-pool piles

    International Nuclear Information System (INIS)

    Trioulaire, M.

    1959-01-01

    In France two swimming-pool piles, Melusine and Triton, have just been set in operation. The swimming-pool pile is the ideal research tool for neutron fluxes of the order of 10 13 . This type of pile can be of immediate interest to many research centres, but its cost must be reduced and a break with tradition should be observed in its design. It would be an advantage: - to bury the swimming-pool; - to reject the experimental channel; - to concentrate the cooling circuit in the swimming-pool; - to carry out all manipulations in the water; - to double the core. (author) [fr

  14. Astrocytes and Glutamate Homoeostasis in Alzheimer's Disease: A Decrease in Glutamine Synthetase, But Not in Glutamate Transporter-1, in the Prefrontal Cortex

    Directory of Open Access Journals (Sweden)

    Magdalena Kulijewicz-Nawrot

    2013-09-01

    Full Text Available Astrocytes control tissue equilibrium and hence define the homoeostasis and function of the CNS (central nervous system. Being principal homoeostatic cells, astroglia are fundamental for various forms of neuropathology, including AD (Alzheimer's disease. AD is a progressive neurodegenerative disorder characterized by the loss of cognitive functions due to specific lesions in mnesic-associated regions, including the mPFC (medial prefrontal cortex. Here, we analyzed the expression of GS (glutamine synthetase and GLT-1 (glutamate transporter-1 in astrocytes in the mPFC during the progression of AD in a triple-transgenic mouse model (3xTg-AD. GS is an astrocyte-specific enzyme, responsible for the intracellular conversion of glutamate into glutamine, whereas the removal of glutamate from the extracellular space is accomplished mainly by astroglia-specific GLT-1. We found a significant decrease in the numerical density (Nv, cells/mm3 of GS-positive astrocytes from early to middle ages (1–9 months; at the age of 1 month by 17%, 6 months by 27% and 9 months by 27% when compared with control animals in parallel with a reduced expression of GS (determined by Western blots, which started at the age of 6 months and was sustained up to 12 months of age. We did not, however, find any changes in the expression of GLT-1, which implies an intact glutamate uptake mechanism. Our results indicate that the decrease in GS expression may underlie a gradual decline in the vital astrocyte-dependent glutamate–glutamine conversion pathway, which in turn may compromise glutamate homoeostasis, leading towards failures in synaptic connectivity with deficient cognition and memory.

  15. Laboratory investigation and simulation of breakthrough curves in karst conduits with pools

    Science.gov (United States)

    Zhao, Xiaoer; Chang, Yong; Wu, Jichun; Peng, Fu

    2017-12-01

    A series of laboratory experiments are performed under various hydrological conditions to analyze the effect of pools in pipes on breakthrough curves (BTCs). The BTCs are generated after instantaneous injections of NaCl tracer solution. In order to test the feasibility of reproducing the BTCs and obtain transport parameters, three modeling approaches have been applied: the equilibrium model, the linear graphical method and the two-region nonequilibrium model. The investigation results show that pools induce tailing of the BTCs, and the shapes of BTCs depend on pool geometries and hydrological conditions. The simulations reveal that the two-region nonequilibrium model yields the best fits to experimental BTCs because the model can describe the transient storage in pools by the partition coefficient and the mass transfer coefficient. The model parameters indicate that pools produce high dispersion. The increased tailing occurs mainly because the partition coefficient decreases, as the number of pools increases. When comparing the tracer BTCs obtained using the two types of pools with the same size, the more appreciable BTC tails that occur for symmetrical pools likely result mainly from the less intense exchange between the water in the pools and the water in the pipe, because the partition coefficients for the two types of pools are virtually identical. Dispersivity values decrease as flow rates increase; however, the trend in dispersion is not clear. The reduced tailing is attributed to a decrease in immobile water with increasing flow rate. It provides evidence for hydrodynamically controlled tailing effects.

  16. Fast inhibition of glutamate-activated currents by caffeine.

    Directory of Open Access Journals (Sweden)

    Nicholas P Vyleta

    Full Text Available BACKGROUND: Caffeine stimulates calcium-induced calcium release (CICR in many cell types. In neurons, caffeine stimulates CICR presynaptically and thus modulates neurotransmitter release. METHODOLOGY/PRINCIPAL FINDINGS: Using the whole-cell patch-clamp technique we found that caffeine (20 mM reversibly increased the frequency and decreased the amplitude of miniature excitatory postsynaptic currents (mEPSCs in neocortical neurons. The increase in mEPSC frequency is consistent with a presynaptic mechanism. Caffeine also reduced exogenously applied glutamate-activated currents, confirming a separate postsynaptic action. This inhibition developed in tens of milliseconds, consistent with block of channel currents. Caffeine (20 mM did not reduce currents activated by exogenous NMDA, indicating that caffeine block is specific to non-NMDA type glutamate receptors. CONCLUSIONS/SIGNIFICANCE: Caffeine-induced inhibition of mEPSC amplitude occurs through postsynaptic block of non-NMDA type ionotropic glutamate receptors. Caffeine thus has both pre and postsynaptic sites of action at excitatory synapses.

  17. Development of INSPCT-S for inspection of spent fuel pool

    Energy Technology Data Exchange (ETDEWEB)

    Walters, W.; Haghighat, A. [Nuclear Engineering Program, Mechanical Engineering Dept., Virginia Tech., Blacksburg, VA 24061 (United States); Sitaraman, S.; Ham, Y. [Lawrence Livermore National Laboratory, 7000 East Ave., Livermore, CA 94550 (United States)

    2011-07-01

    In this paper, we discuss an accurate and fast software tool (INSPCT-S, Inspection of Nuclear Spent fuel-Pool Calculation Tool, version Spreadsheet) developed for calculation of the response of fission chambers placed in a spent fuel pool, such as Atucha-I. INSPCT-S is developed for identification of suspicious regions of the pool that may have missing or substitute assemblies. INSPCT-S uses a hybrid algorithm based on the adjoint function methodology. The neutron source is comprised of spontaneous fission, ({alpha}, n) interactions, and subcritical multiplication. The former is evaluated using the ORIGEN-ARP code, and the latter is obtained with the fission matrix (FM) formulation. The FM coefficients are determined using the MCNP Monte Carlo code, and the importance function is determined using the PENTRAN 3-D parallel Sn code. Three databases for the neutron source, FM elements, and adjoint flux are prepared as functions of different parameters including burnup, cooling time, enrichment, and pool lattice size. INSPCT-S uses the aforementioned databases and systems of equations to calculate detector responses, which are subsequently compared with normalized experimental data. If this comparison is not satisfied, INSPCT-S utilizes color coding to identify the suspicious regions of a spent fuel pool. (authors)

  18. The Challenge of Interpreting Glutamate-Receptor Ion-Channel Structures.

    Science.gov (United States)

    Mayer, Mark L

    2017-11-21

    Ion channels activated by glutamate mediate excitatory synaptic transmission in the central nervous system. Similar to other ligand-gated ion channels, their gating cycle begins with transitions from a ligand-free closed state to glutamate-bound active and desensitized states. In an attempt to reveal the molecular mechanisms underlying gating, numerous structures for glutamate receptors have been solved in complexes with agonists, antagonists, allosteric modulators, and auxiliary proteins. The embarrassingly rich library of structures emerging from this work reveals very dynamic molecules with a more complex conformational spectrum than anticipated from functional studies. Unanticipated conformations solved for complexes with competitive antagonists and a lack of understanding of the structural basis for ion channel subconductance states further highlight challenges that have yet to be addressed. Published by Elsevier Inc.

  19. An evaluation of different target enrichment methods in pooled sequencing designs for complex disease association studies.

    Directory of Open Access Journals (Sweden)

    Aaron G Day-Williams

    Full Text Available Pooled sequencing can be a cost-effective approach to disease variant discovery, but its applicability in association studies remains unclear. We compare sequence enrichment methods coupled to next-generation sequencing in non-indexed pools of 1, 2, 10, 20 and 50 individuals and assess their ability to discover variants and to estimate their allele frequencies. We find that pooled resequencing is most usefully applied as a variant discovery tool due to limitations in estimating allele frequency with high enough accuracy for association studies, and that in-solution hybrid-capture performs best among the enrichment methods examined regardless of pool size.

  20. Development of a novel ultrasensitive enzyme immunoassay for human glutamic acid decarboxylase 65 antibody.

    Science.gov (United States)

    Numata, Satoshi; Katakami, Hideki; Inoue, Shinobu; Sawada, Hirotake; Hashida, Seiichi

    2016-07-01

    We developed a novel, ultrasensitive enzyme immunoassay (immune complex transfer enzyme immunoassay) for determination of glutamic acid decarboxylase autoantibody concentrations in serum samples from patients with type 2 diabetes. We developed an immune complex transfer enzyme immunoassay for glutamic acid decarboxylase autoantibody and measured glutamic acid decarboxylase autoantibody from 22 patients with type 1 diabetes, 29 patients with type 2 diabetes, and 32 healthy controls. A conventional ELISA kit identified 10 patients with type 1 diabetes and one patient with type 2 diabetes as glutamic acid decarboxylase autoantibody positive, whereas 15 patients with type 1 diabetes and six patients with type 2 diabetes were identified as glutamic acid decarboxylase autoantibody positive using immune complex transfer enzyme immunoassay. Immune complex transfer enzyme immunoassay is a highly sensitive and specific assay for glutamic acid decarboxylase autoantibody and might be clinically useful for diabetic onset prediction and early diagnosis. © The Author(s) 2016.

  1. Oral glutamate intake reduces acute and chronic effects of ethanol in ...

    African Journals Online (AJOL)

    treatment, male Wistar rats were trained to consume ethanol-sucrose solution during a 2-h period daily, ... Oral treatment with 2.5 g/kg of glutamate reversed the acute motor effects of ethanol. ..... glutamate release in the prefrontal cortex-NAc.

  2. Characterization of the venom from the spider, Araneus gemma: search for a glutamate antagonist

    International Nuclear Information System (INIS)

    Early, S.L.

    1985-01-01

    Venom from three spiders, Argiope aurantia, Neoscona arabesca, and Araneus gemma have been shown to inhibit the binding of L-[ 3 H]glutamate to both GBP and synaptic membranes. The venom from Araneus gemma was shown to be the most potent of the three venoms in inhibiting the binding of L-[ 3 H]glutamate to GBP. Therefore, Araneus gemma venom was selected for further characterization. Venom from Araneus gemma appeared to contain two factors which inhibit the binding of L-[ 3 H]glutamate to GBP and at least one factor that inhibits L-glutamate-stimulated 35 SCN flux. Factor I is thought to be L-glutamic acid, based on: (1) its similar mobility to glutamic acid in thin-layer chromatography and amino acid analysis, (2) the presence of fingerprint molecular ion peaks for glutamate in the mass spectrum for the methanol:water (17:1) extract and for the fraction from the HPLC-purification of the crude venom, and (3) its L-glutamate-like interaction with the sodium-dependent uptake system. Factor II appears to be a polypeptide, possibly 21 amino acids in length, and does not appear to contain any free amino groups or tryptophan. While the venom does not appear to contain any indoleamines, three catecholamines (epinephrine, epinine, dopamine) and one catecholamine metabolite (DOPAC) were detected

  3. Effect of parenteral glutamate treatment on the localization of neurotransmitters in the mediobasal hypothalamus

    Energy Technology Data Exchange (ETDEWEB)

    Walaas, I; Fonnum, F

    1978-01-01

    The localization of cholinergic, aminergic and amino acid-ergic neurones in the mediobasal hypothalamus has been studied in normal rat brain and in brains where neurones in nucleus arcuatus were destroyed by repeated administration of 2 mg/g body weight monosodium glutamate to newborn animals. In normal animals acetylcholinesterase staining, choline acetyltransferase and aromatic L-amino acid decarboxylase were concentrated in the median eminence and the arcuate nucleus. Glutamate decarboxylase was concentrated at the boundary between the ventromedial and the arcuate nuclei, with lower activity in the arcuate nucleus and very low activity in the median eminence. Nucleus arcuatus contained an intermediate level of high affinity glutamate uptake. In the lesioned animals, there were significant decreases in choline acetyltransferase, acetylcholinesterase staining and glutamate decarboxylase in the median eminence, whereas choline acetyltransferase activity and acetylcholinesterase staining, but not glutamate decarboxylase activity, were decreased in nucleus arcuatus. Aromatic L-amino acid decarboxylase was unchanged in all regions studied. The high affinity uptakes of glutamate, dopamine and noradrenaline, and the endogenous amino acid levels were also unchanged in the treated animals. The results indicate the existence of acetylcholine- and GABA-containing elements in the tuberoinfundibular tract. They further indicate that the dopamine cells in the arcuate nucleus are less sensitive to the toxic effect of glutamate than other cell types, possibly because they contain less glutamate receptors.

  4. Silicon Wafer-Based Platinum Microelectrode Array Biosensor for Near Real-Time Measurement of Glutamate in Vivo

    Directory of Open Access Journals (Sweden)

    Nigel T. Maidment

    2008-08-01

    Full Text Available Using Micro-Electro-Mechanical-Systems (MEMS technologies, we have developed silicon wafer-based platinum microelectrode arrays (MEAs modified with glutamate oxidase (GluOx for electroenzymatic detection of glutamate in vivo. These MEAs were designed to have optimal spatial resolution for in vivo recordings. Selective detection of glutamate in the presence of the electroactive interferents, dopamine and ascorbic acid, was attained by deposition of polypyrrole and Nafion. The sensors responded to glutamate with a limit of detection under 1μM and a sub-1-second response time in solution. In addition to extensive in vitro characterization, the utility of these MEA glutamate biosensors was also established in vivo. In the anesthetized rat, these MEA glutamate biosensors were used for detection of cortically-evoked glutamate release in the ventral striatum. The MEA biosensors also were applied to the detection of stress-induced glutamate release in the dorsal striatum of the freely-moving rat.

  5. Focal and temporal release of glutamate in the mushroom bodies improves olfactory memory in Apis mellifera.

    Science.gov (United States)

    Locatelli, Fernando; Bundrock, Gesine; Müller, Uli

    2005-12-14

    In contrast to vertebrates, the role of the neurotransmitter glutamate in learning and memory in insects has hardly been investigated. The reason is that a pharmacological characterization of insect glutamate receptors is still missing; furthermore, it is difficult to locally restrict pharmacological interventions. In this study, we overcome these problems by using locally and temporally defined photo-uncaging of glutamate to study its role in olfactory learning and memory formation in the honeybee, Apis mellifera. Uncaging glutamate in the mushroom bodies immediately after a weak training protocol induced a higher memory rate 2 d after training, mimicking the effect of a strong training protocol. Glutamate release before training does not facilitate memory formation, suggesting that glutamate mediates processes triggered by training and required for memory formation. Uncaging glutamate in the antennal lobes shows no effect on memory formation. These results provide the first direct evidence for a temporally and locally restricted function of glutamate in memory formation in honeybees and insects.

  6. Corium quench in deep pool mixing experiments

    International Nuclear Information System (INIS)

    Spencer, B.W.; McUmber, L.; Gregorash, D.; Aeschlimann, R.; Sienicki, J.J.

    1985-01-01

    The results of two recent corium-water thermal interaction (CWTI) tests are described in which a stream of molten corium was poured into a deep pool of water in order to determine the mixing behavior, the corium-to-water heat transfer rates, and the characteristic sizes of the quenched debris. The corium composition was 60% UO 2 , 16% ZrO 2 , and 24% stainless steel by weight; its initial temperature was 3080 K, approx.160 K above the oxide phase liquidus temperature. The corium pour stream was a single-phase 2.2 cm dia liquid column which entered the water pool in film boiling at approx.4 m/s. The water subcooling was 6 and 75C in the two tests. Test results showed that with low subcooling, rapid steam generation caused the pool to boil up into a high void fraction regime. In contrast, with large subcooling no net steam generation occurred, and the pool remained relatively quiescent. Breakup of the jet appeared to occur by surface stripping. In neither test was the breakup complete during transit through the 32 cm deep water pool, and molten corium channeled to the base where it formed a melt layer. The characteristic heat transfer rates measured 3.5 MJ/s and 2.7 MJ/s during the fall stage for small and large subcooling, respectively; during the initial stage of bed quench, the surface heat fluxes measured 2.4 MW/m 2 and 3.7 MW/m 2 , respectively. A small mass of particles was formed in each test, measuring typically 0.1 to 1 mm and 1 to 5 mm dia for the large and small subcooling conditions, respectively. 9 refs., 13 figs., 1 tab

  7. Dual and Direction-Selective Mechanisms of Phosphate Transport by the Vesicular Glutamate Transporter

    Directory of Open Access Journals (Sweden)

    Julia Preobraschenski

    2018-04-01

    Full Text Available Summary: Vesicular glutamate transporters (VGLUTs fill synaptic vesicles with glutamate and are thus essential for glutamatergic neurotransmission. However, VGLUTs were originally discovered as members of a transporter subfamily specific for inorganic phosphate (Pi. It is still unclear how VGLUTs accommodate glutamate transport coupled to an electrochemical proton gradient ΔμH+ with inversely directed Pi transport coupled to the Na+ gradient and the membrane potential. Using both functional reconstitution and heterologous expression, we show that VGLUT transports glutamate and Pi using a single substrate binding site but different coupling to cation gradients. When facing the cytoplasm, both ions are transported into synaptic vesicles in a ΔμH+-dependent fashion, with glutamate preferred over Pi. When facing the extracellular space, Pi is transported in a Na+-coupled manner, with glutamate competing for binding but at lower affinity. We conclude that VGLUTs have dual functions in both vesicle transmitter loading and Pi homeostasis within glutamatergic neurons. : Preobraschenski et al. show that the vesicular glutamate transporter functions as a bi-directional phosphate transporter that is coupled with different cations in each direction and hence may play a key role in neuronal phosphate homeostasis. Keywords: VGLUT, SLC17 family, type I Na+-dependent inorganic phosphate transporter, ATPase, proteoliposomes, hybrid vesicles, anti-VGLUT1 nanobody

  8. Biosynthetic preparation of L-[13C]- and [15N]glutamate by Brevibacterium flavum

    International Nuclear Information System (INIS)

    Walker, T.E.; London, R.E.

    1987-01-01

    The biosynthesis of isotopically labeled L-glutamic acid by the microorganism Brevibacterium flavum was studied with a variety of carbon-13-enriched precursors. The purpose of this study was twofold: (i) to develop techniques for the efficient preparation of labeled L-glutamate with a variety of useful labeling patterns which can be used for other metabolic studies, and (ii) to better understand the metabolic events leading to label scrambling in these strains. B. flavum, which is used commercially for the production of monosodium glutamate, has the capability of utilizing glucose or acetate as a sole carbon source, and important criterion from the standpoint of developing labeling strategies. Unfortunately, singly labeled glucose precursors lead to excessive isotopic dilution which reduces their usefulness. Studies with [3- 13 C]pyruvate indicate that this problem can in principle be overcome by using labeled three-carbon precursors; however, conditions could not be found which would lead to an acceptable yield of isotopically labeled L-glutamate. In contrast, [1- 13 C]- or [2- 13 C]acetate provides relatively inexpensive, readily available precursors for the production of selectively labeled, high enriched L-glutamate. The preparation of L-[ 15 N]glutamate from [ 15 N]ammonium sulfate was carried out and is a very effective labeling strategy. Analysis of the isotopic distribution in labeled glutamate provides details about the metabolic pathways in these interesting organisms

  9. Peripheral Glutamate Receptors Are Required for Hyperalgesia Induced by Capsaicin

    Directory of Open Access Journals (Sweden)

    You-Hong Jin

    2012-01-01

    Full Text Available Transient receptor potential vanilloid1 (TRPV1 and glutamate receptors (GluRs are located in small diameter primary afferent neurons (nociceptors, and it was speculated that glutamate released in the peripheral tissue in response to activation of TRPV1 might activate nociceptors retrogradely. But, it was not clear which types of GluRs are functioning in the nociceptive sensory transmission. In the present study, we examined the c-Fos expression in spinal cord dorsal horn following injection of drugs associated with glutamate receptors with/without capsaicin into the hindpaw. The subcutaneous injection of capsaicin or glutamate remarkably evoked c-Fos expression in ipsilateral sides of spinal cord dorsal horn. This capsaicin evoked increase of c-Fos expression was significantly prevented by concomitant administration of MK801, CNQX, and CPCCOEt. On the other hand, there were not any significant changes in coinjection of capsaicin and MCCG or MSOP. These results reveal that the activation of iGluRs and group I mGluR in peripheral afferent nerves play an important role in mechanisms whereby capsaicin evokes/maintains nociceptive responses.

  10. Spent fuel storage pool

    International Nuclear Information System (INIS)

    Murakami, Naoshi.

    1996-01-01

    Fences are disposed to a fuel exchange floor surrounding the upper surface of a fuel pool for preventing overflow of pool water. The fences comprise a plurality of flat boards arranged in parallel with each other in the longitudinal direction while being vertically inclined, and slits are disposed between the boards for looking down the pool. Further, the fences comprise wide boards and are constituted so as to be laid horizontally on the fuel exchange floor in a normal state and uprisen by means of the signals from an earthquake sensing device. Even if pool water is overflow from the fuel pool by the vibrations occurred upon earthquake and flown out to the floor of the fuel exchange floor, the overflow from the fuel exchange floor is prevented by the fences. An operator who monitors the fuel pool can observe the inside of the fuel pool through the slits formed to the fences during normal operation. The fences act as resistance against overflowing water upon occurrence of an earthquake thereby capable of reducing the overflowing amount of water due to the vibrations of pool water. The effect of preventing overflowing water can be enhanced. (N.H.)

  11. Exercise induced upregulation of glutamate-cysteine ligase catalytic subunit and glutamate-cysteine ligase modifier subunit gene expression in Thoroughbred horses

    Directory of Open Access Journals (Sweden)

    Jeong-Woong Park

    2017-05-01

    Full Text Available Objective This study was performed to reveal the molecular structure and expression patterns of horse glutamate-cysteine ligase catalytic subunit (GCLC and glutamate-cysteine ligase modifier subunit (GCLM genes whose products form glutamate cysteine ligase, which were identified as differentially expressed genes in the previous study. Methods We performed bioinformatics analyses, and gene expression assay with quantitative polymerase chain reaction (qPCR for horse GCLC and GCLM genes in muscle and blood leukocytes of Thoroughbred horses Results Expression of GCLC showed the same pattern in both blood and muscle tissues after exercise. Expression of GCLC increased in the muscle and blood of Thoroughbreds, suggesting a tissue-specific regulatory mechanism for the expression of GCLC. In addition, expression of the GCLM gene increased after exercise in both the blood and muscle of Thoroughbreds. Conclusion We established the expression patterns of GCLC and GCLM in the skeletal muscle and blood of Thoroughbred horses in response to exercise. Further study is now warranted to uncover the functional importance of these genes in exercise and recovery in racehorses.

  12. Riluzole protects against glutamate-induced slowing of neurofilament axonal transport.

    LENUS (Irish Health Repository)

    Stevenson, Alison

    2009-04-24

    Riluzole is the only drug approved for the treatment of amyotrophic lateral sclerosis (ALS) but its precise mode of action is not properly understood. Damage to axonal transport of neurofilaments is believed to be part of the pathogenic mechanism in ALS and this has been linked to defective glutamate handling and increased phosphorylation of neurofilament side-arm domains. Here, we show that riluzole protects against glutamate-induced slowing of neurofilament transport. Protection is associated with decreased neurofilament side-arm phosphorylation and inhibition of the activities of two neurofilament kinases, ERK and p38 that are activated in ALS. Thus, the anti-glutamatergic properties of riluzole include protection against glutamate-induced changes to neurofilament phosphorylation and transport.

  13. Performance of a swimming pool heating system by utilizing waste energy rejected from an ice rink with an energy storage tank

    International Nuclear Information System (INIS)

    Kuyumcu, Muhammed Enes; Tutumlu, Hakan; Yumrutaş, Recep

    2016-01-01

    Highlights: • An analytical model of the system, and a computational program were developed. • Transient behavior of the water in the buried energy storage tank was simulated. • Effects of various system parameters on the system performance were investigated. • Long period performance of the system was analyzed and obtained periodic condition. • Optimum ice rink size is determined for a semi-Olympic size swimming pool heating. - Abstract: This study deals with determining the long period performance of a swimming pool heating system by utilizing waste heat energy that is rejected from a chiller unit of ice rink and subsequently stored in an underground thermal energy storage (TES) tank. The system consists of an ice rink, a swimming pool, a spherical underground TES tank, a chiller and a heat pump. The ice rink and the swimming pool are both enclosed and located in Gaziantep, Turkey. An analytical model was developed to obtain the performance of the system using Duhamel’s superposition and similarity transformation techniques. A computational model written in MATLAB program based on the transient heat transfer is used to obtain the annual variation of the ice rink and the swimming pool energy requirements, the water temperature in the TES tank, COP, and optimum ice rink size depending on the different ground, TES tank, chiller, and heat pump characteristics. The results obtained from the analysis indicate that 6–7 years’ operational time span is necessary to obtain the annual periodic operation condition. In addition, an ice rink with a size of 475 m"2 gives the optimum performance of the system with a semi-Olympic size swimming pool (625 m"2).

  14. On the potential role of glutamate transport in mental fatigue

    Directory of Open Access Journals (Sweden)

    Hansson Elisabeth

    2004-11-01

    Full Text Available Abstract Mental fatigue, with decreased concentration capacity, is common in neuroinflammatory and neurodegenerative diseases, often appearing prior to other major mental or physical neurological symptoms. Mental fatigue also makes rehabilitation more difficult after a stroke, brain trauma, meningitis or encephalitis. As increased levels of proinflammatory cytokines are reported in these disorders, we wanted to explore whether or not proinflammatory cytokines could induce mental fatigue, and if so, by what mechanisms. It is well known that proinflammatory cytokines are increased in major depression, "sickness behavior" and sleep deprivation, which are all disorders associated with mental fatigue. Furthermore, an influence by specific proinflammatory cytokines, such as interleukin (IL-1, on learning and memory capacities has been observed in several experimental systems. As glutamate signaling is crucial for information intake and processing within the brain, and due to the pivotal role for glutamate in brain metabolism, dynamic alterations in glutamate transmission could be of pathophysiological importance in mental fatigue. Based on this literature and observations from our own laboratory and others on the role of astroglial cells in the fine-tuning of glutamate neurotransmission we present the hypothesis that the proinflammatory cytokines tumor necrosis factor-α, IL-1β and IL-6 could be involved in the pathophysiology of mental fatigue through their ability to attenuate the astroglial clearance of extracellular glutamate, their disintegration of the blood brain barrier, and effects on astroglial metabolism and metabolic supply for the neurons, thereby attenuating glutamate transmission. To test whether our hypothesis is valid or not, brain imaging techniques should be applied with the ability to register, over time and with increasing cognitive loading, the extracellular concentrations of glutamate and potassium (K+ in humans suffering from

  15. Glutamate and dopamine in schizophrenia: an update for the 21st century

    Science.gov (United States)

    Howes, Oliver; McCutcheon, Rob; Stone, James

    2016-01-01

    The glutamate and dopamine hypotheses are leading theories of the pathoaetiology of schizophrenia. Both were initially based on indirect evidence from pharmacological studies supported by post-mortem findings, but have since been substantially advanced by new lines of evidence from in vivo imaging studies. This review provides an up- date on the latest findings on dopamine and glutamate abnormalities in schizophrenia, focusing on the in vivo neuroimaging studies in patients and clinical high risk groups, and considers their implications for understanding the biology and treatment of schizophrenia. These findings have refined both the dopamine and glutamate hypotheses, enabling greater anatomical and functional specificity, and have been complemented by preclinical evidence showing how the risk factors for schizophrenia impact on the dopamine and glutamate systems. The implications of this new evidence for understanding the development and treatment of schizophrenia are considered, and the gaps in current knowledge highlighted. Finally the evidence for an integrated model of the interactions between the glutamate and dopamine systems is reviewed, and future directions discussed. PMID:25586400

  16. Dysfunctional TCA-Cycle Metabolism in Glutamate Dehydrogenase Deficient Astrocytes

    DEFF Research Database (Denmark)

    Nissen, Jakob D; Pajęcka, Kamilla; Stridh, Malin H

    2015-01-01

    aminotransferase (AAT) catalyze the reversible reaction between glutamate and α-ketoglutarate, which is the initial step for glutamate to enter TCA cycle metabolism. In contrast to GDH, AAT requires a concomitant interconversion of oxaloacetate and aspartate. We have investigated the role of GDH in astrocyte...... Labeling of aspartate and TCA cycle intermediates confirmed that the increased amount of aspartate is associated with elevated TCA cycle flux from α-ketoglutarate to oxaloacetate, i.e. truncated TCA cycle. (13) C Glucose metabolism was elevated in GDH deficient astrocytes as observed by increased de novo...... synthesis of aspartate via pyruvate carboxylation. In the absence of glucose, lactate production from glutamate via malic enzyme was lower in GDH deficient astrocytes. In conclusions, our studies reveal that metabolism via GDH serves an important anaplerotic role by adding net carbon to the TCA cycle...

  17. Aminotransferase and glutamate dehydrogenase activities in lactobacilli and streptococci

    Directory of Open Access Journals (Sweden)

    Guillermo Hugo Peralta

    Full Text Available ABSTRACT Aminotransferases and glutamate dehydrogenase are two main types of enzymes involved in the initial steps of amino acid catabolism, which plays a key role in the cheese flavor development. In the present work, glutamate dehydrogenase and aminotransferase activities were screened in twenty one strains of lactic acid bacteria of dairy interest, either cheese-isolated or commercial starters, including fifteen mesophilic lactobacilli, four thermophilic lactobacilli, and two streptococci. The strains of Streptococcus thermophilus showed the highest glutamate dehydrogenase activity, which was significantly elevated compared with the lactobacilli. Aspartate aminotransferase prevailed in most strains tested, while the levels and specificity of other aminotransferases were highly strain- and species-dependent. The knowledge of enzymatic profiles of these starter and cheese-isolated cultures is helpful in proposing appropriate combinations of strains for improved or increased cheese flavor.

  18. Effects of pentylenetetrazole and glutamate on metabolism of [U-(13)C]glucose in cultured cerebellar granule neurons.

    Science.gov (United States)

    Eloqayli, Haytham; Qu, Hong; Unsgård, Geirmund; Sletvold, Olav; Hadidi, Hakam; Sonnewald, Ursula

    2002-02-01

    This study was performed to analyze the effects of glutamate and the epileptogenic agent pentylenetetrazole (PTZ) on neuronal glucose metabolism. Cerebellar granule neurons were incubated for 2 h in medium containing 3 mM [U-(13)C]glucose, with and without 0.25 mM glutamate and/or 10 mM PTZ. In the presence of PTZ, decreased glucose consumption with unchanged lactate release was observed, indicating decreased glucose oxidation. PTZ also slowed down tricarboxylic acid (TCA) cycle activity as evidenced by the decreased amounts of labeled aspartate and [1,2-(13)C]glutamate. When glutamate was present, glucose consumption was also decreased. However, the amount of glutamate, derived from [U-(13)C]glucose via the first turn of the TCA cycle, was increased. The decreased amount of [1,2-(13)C]glutamate, derived from the second turn in the TCA cycle, and increased amount of aspartate indicated the dilution of label due to the entrance of unlabeled glutamate into TCA cycle. In the presence of glutamate plus PTZ, the effect of PTZ was enhanced by glutamate. Labeled alanine was detected only in the presence of glutamate plus PTZ, which indicated that oxaloacetate was a better amino acid acceptor than pyruvate. Furthermore, there was also evidence for intracellular compartmentation of oxaloacetate metabolism. Glutamate and PTZ caused similar metabolic changes, however, via different mechanisms. Glutamate substituted for glucose as energy substrate in the TCA cycle, whereas, PTZ appeared to decrease mitochondrial activity.

  19. Observations of Cold Pool Properties during GoAmazon2014/5

    Science.gov (United States)

    Mayne, S. L.; Schumacher, C.; MacDonald, L.; Turner, D. D.

    2017-12-01

    Convectively generated cold pools are instrumental in both the development of the sub-cloud layer and the organization of deep convection. Despite this, analyses of cold pools in the tropics are constrained by a lack of observational data; insight into the phenomena therefore relies heavily on numerical models. GoAmazon2014/5, a 2-year DOE-sponsored field campaign centered on Manacapuru, Brazil in the central Amazon, provides a unique opportunity to characterize tropical cold pools and allows for the comparison of observational data with theoretical results from model cold pool simulations and parameterizations. This investigation analyzes radar, disdrometer, and profiler measurements at the DOE mobile facility site to study tropical cold pool characteristics. The Brazilian military (SIPAM) operational S-band radar in Manaus is used to provide a broad context of convective systems, while measurements from Parsivel disdrometers are used to assess drop-size distributions (DSDs) at the surface. A unique aspect of this research is the use of the Atmospheric Emitted Radiance Interferometer (AERI) instrument, which utilizes down-welling IR measurements to obtain vertical profiles of thermodynamic quantities such as temperature and water vapor in the lowest few km of the atmosphere. Combined with surface observations and sounding data, these datasets will result in a thorough investigation of the horizontal and vertical characteristics of cold pools over the tropical rain forest. Preliminary analyses of 20 events reveal a mean cold pool height of 220 m and a mean radius of approximately 8.5 km. The average cold pool experienced a temperature (specific humidity) decrease of approximately 1 K (0.4 g/kg) at the surface. The temperature decrease is consistent with modeling studies and limited observations from previous studies over the tropics. The small decrease in specific humidity is attributed to the high moisture content within the cold pools. AERI retrievals of

  20. Distinct roles of two anaplerotic pathways in glutamate production induced by biotin limitation in Corynebacterium glutamicum.

    Science.gov (United States)

    Sato, Hiroki; Orishimo, Keita; Shirai, Tomokazu; Hirasawa, Takashi; Nagahisa, Keisuke; Shimizu, Hiroshi; Wachi, Masaaki

    2008-07-01

    Corynebacterium glutamicum is a biotin auxotrophic bacterium in which glutamate production is induced under biotin-limited conditions. During glutamate production, anaplerotic reactions catalyzed by phosphoenolpyruvate carboxylase (PEPC) and a biotin-containing enzyme pyruvate carboxylase (PC) are believed to play an important role in supplying oxaloacetate in the tricarboxylic acid cycle. To understand the distinct roles of PEPC and PC on glutamate production by C. glutamicum, we observed glutamate production induced under biotin-limited conditions in the disruptants of the genes encoding PEPC (ppc) and PC (pyc), respectively. The pyc disruptant retained the ability to produce high amounts of glutamate, and lactate was simultaneously produced probably due to the increased intracellular pyruvate levels. On the other hand, the ppc knockout mutant could not produce glutamate. Additionally, glutamate production in the pyc disruptant was enhanced by overexpression of ppc rather than disruption of the lactate dehydrogenase gene (ldh), which is involved in lactate production. Metabolic flux analysis based on the 13C-labeling experiment and measurement of 13C-enrichment in glutamate using nuclear magnetic resonance spectroscopy revealed that the flux for anaplerotic reactions in the pyc disruptant was lower than that in the wild type, concomitantly increasing the flux for lactate formation. Moreover, overexpression of ppc increased this flux in both the pyc disruptant and the wild type. Our results suggest that the PEPC-catalyzed anaplerotic reaction is necessary for glutamate production induced under biotin-limited conditions, because PC is not active during glutamate production, and overexpression of ppc effectively enhances glutamate production under biotin-limited conditions.

  1. Label Free Detection of L-Glutamate Using Microfluidic Based Thermal Biosensor

    Directory of Open Access Journals (Sweden)

    Varun Lingaiah Kopparthy

    2015-01-01

    Full Text Available A thermoelectric biosensor for the detection of L-glutamate concentration was developed. The thermoelectric sensor is integrated into a micro-calorimeter which measures the heat produced by biochemical reactions. The device contains a single flow channel that is 120 µm high and 10 mm wide with two fluid inlets and one fluid outlet. An antimony-bismuth (Sb-Bi thermopile with high common mode rejection ratio is attached to the lower channel wall and measures the dynamic changes in the temperature when L-glutamate undergoes oxidative deamination in the presence of glutamate oxidase (GLOD. The thermopile has a Seebeck coefficient of ~7 µV·(m·K−1. The device geometry, together with hydrodynamic focusing, eliminates the need of extensive temperature control. Layer-by-layer assembly is used to immobilize GLOD on the surface of glass coverslips by alternate electrostatic adsorption of polyelectrolyte and GLOD. The impulse injection mode using a 6-port injection valve minimizes sample volume to 5 µL. The sensitivity of the sensor for glutamate is 17.9 nVs·mM−1 in the linear range of 0–54 mM with an R2 value of 0.9873. The lowest detection limit of the sensor for glutamate is 5.3 mM.

  2. Anhydrous thallium hydrogen L-glutamate: polymer networks formed by sandwich layers of oxygen-coordinated thallium ions cores shielded by hydrogen L-glutamate counterions.

    Science.gov (United States)

    Bodner, Thomas; Wirnsberger, Bianca; Albering, Jörg; Wiesbrock, Frank

    2011-11-07

    Anhydrous thallium hydrogen L-glutamate [Tl(L-GluH)] crystallizes from water (space group P2(1)) with a layer structure in which the thallium ions are penta- and hexacoordinated exclusively by the oxygen atoms of the γ-carboxylate group of the hydrogen L-glutamate anions to form a two-dimensional coordination polymer. The thallium-oxygen layer is composed of Tl(2)O(2) and TlCO(2) quadrangles and is only 3 Å high. Only one hemisphere of the thallium ions participates in coordination, indicative of the presence of the 6s(2) lone pair of electrons. The thallium-oxygen assemblies are shielded by the hydrogen l-glutamate anions. Only the carbon atom of the α-carboxylate group deviates from the plane spanned by the thallium ions, the γ-carboxylate groups and the proton bearing carbon atoms, which are in trans conformation. Given the abundance of L-glutamic and L-aspartic acid in biological systems on the one hand and the high toxicity of thallium on the other hand, it is worth mentioning that the dominant structural motifs in the crystal structure of [Tl(L-GluH)] strongly resemble their corresponding analogues in the crystalline phase of [K(L-AspH)(H(2)O)(2)].

  3. Glutamate as a neurotransmitter in the brain: review of physiology and pathology.

    Science.gov (United States)

    Meldrum, B S

    2000-04-01

    Glutamate is the principal excitatory neurotransmitter in brain. Our knowledge of the glutamatergic synapse has advanced enormously in the last 10 years, primarily through application of molecular biological techniques to the study of glutamate receptors and transporters. There are three families of ionotropic receptors with intrinsic cation permeable channels [N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainate]. There are three groups of metabotropic, G protein-coupled glutamate receptors (mGluR) that modify neuronal and glial excitability through G protein subunits acting on membrane ion channels and second messengers such as diacylglycerol and cAMP. There are also two glial glutamate transporters and three neuronal transporters in the brain. Glutamate is the most abundant amino acid in the diet. There is no evidence for brain damage in humans resulting from dietary glutamate. A kainate analog, domoate, is sometimes ingested accidentally in blue mussels; this potent toxin causes limbic seizures, which can lead to hippocampal and related pathology and amnesia. Endogenous glutamate, by activating NMDA, AMPA or mGluR1 receptors, may contribute to the brain damage occurring acutely after status epilepticus, cerebral ischemia or traumatic brain injury. It may also contribute to chronic neurodegeneration in such disorders as amyotrophic lateral sclerosis and Huntington's chorea. In animal models of cerebral ischemia and traumatic brain injury, NMDA and AMPA receptor antagonists protect against acute brain damage and delayed behavioral deficits. Such compounds are undergoing testing in humans, but therapeutic efficacy has yet to be established. Other clinical conditions that may respond to drugs acting on glutamatergic transmission include epilepsy, amnesia, anxiety, hyperalgesia and psychosis.

  4. Glutamic acid decarboxylase isoform distribution in transgenic mouse septum: an anti-GFP immunofluorescence study.

    Science.gov (United States)

    Verimli, Ural; Sehirli, Umit S

    2016-09-01

    The septum is a basal forebrain region located between the lateral ventricles in rodents. It consists of lateral and medial divisions. Medial septal projections regulate hippocampal theta rhythm whereas lateral septal projections are involved in processes such as affective functions, memory formation, and behavioral responses. Gamma-aminobutyric acidergic neurons of the septal region possess the 65 and 67 isoforms of the enzyme glutamic acid decarboxylase. Although data on the glutamic acid decarboxylase isoform distribution in the septal region generally appears to indicate glutamic acid decarboxylase 67 dominance, different studies have given inconsistent results in this regard. The aim of this study was therefore to obtain information on the distributions of both of these glutamic acid decarboxylase isoforms in the septal region in transgenic mice. Two animal groups of glutamic acid decarboxylase-green fluorescent protein knock-in transgenic mice were utilized in the experiment. Brain sections from the region were taken for anti-green fluorescent protein immunohistochemistry in order to obtain estimated quantitative data on the number of gamma-aminobutyric acidergic neurons. Following the immunohistochemical procedures, the mean numbers of labeled cells in the lateral and medial septal nuclei were obtained for the two isoform groups. Statistical analysis yielded significant results which indicated that the 65 isoform of glutamic acid decarboxylase predominates in both lateral and medial septal nuclei (unpaired two-tailed t-test p glutamic acid decarboxylase isoform 65 in the septal region in glutamic acid decarboxylase-green fluorescent protein transgenic mice.

  5. Influence of UV-A or UV-B light and of the nitrogen source on the induction of ferredoxin-dependent glutamate synthase in etiolated tomato cotyledons

    International Nuclear Information System (INIS)

    Migge, A.; Carrayol, E.; Hirel, B.; Lohmann, M.; Meya, G.; Becker, T.W.

    1998-01-01

    The influence of ultraviolet A (UV-A) or B (UV-B) light and of the nitrogen source on the induction of ferredoxin-dependent glutamate synthase (Fd-GOGAT, EC 1.4.7.1) was examined in etiolated cotyledons of tomato (Lycopersicon escu- lentum L.). The Fd-GOGAT activity increased upon illumination of etiolated tomato cotyledons with UV-A or UV-B light. This stimulation of Fd-GOGAT activity was correlated with an increase in both the Fd-GOGAT transcript level and the Fd-GOGAT protein abundance. These results suggest that UV-A or UV-B light stimulates the de novo synthesis of Fd-GOGAT in etiolated tomato cotyledons. Both UV-A and UV-B light failed to influence the activity of NADH-GOGAT (EC 1.4.1.14) in etiolated tomato cotyledons. Taken together, our data indicate that the tomato genes encoding Fd- or NADH-dependent glutamate synthase are regulated differently by UV-A or UV-B light. No difference with respect to both the Fd-GOGAT transcript and protein abundance was found between cotyledons of tomato seedlings grown with either nitrate or ammonium as the sole N-source in the dark or in white light. In addition, the increase in the Fd-GOGAT protein pool induced by white light in etiolated nitrate-grown tomato seedling cotyledons was similar to that induced by white light in etiolated ammonium-grown tomato seedling cotyledons. These results show that the tomato Fd-GOGAT protein level does not depend strongly on the nature of the nitrogen source and that there appears to be no major stimulatory effect on the Fd-GOGAT protein pool produced by nitrate during the illumination of etiolated tomato cotyledons

  6. Quantitative autoradiographic distribution of L-[3H]glutamate-binding sites in rat central nervous system

    International Nuclear Information System (INIS)

    Greenamyre, J.T.; Young, A.B.; Penney, J.B.

    1984-01-01

    Quantitative autoradiography was used to determine the distribution of L-[3H]glutamate-binding sites in the rat central nervous system. Autoradiography was carried out in the presence of Cl- and Ca2+ ions. Scatchard plots and Hill coefficients of glutamate binding suggested that glutamate was interacting with a single population of sites having a K-D of about 300 nM and a capacity of 14.5 pmol/mg of protein. In displacement studies, ibotenate also appeared to bind to a single class of non-interacting sites with a KI of 28 microM. However, quisqualate displacement of [3H]glutamate binding revealed two well-resolved sites with KIS of 12 nM and 114 microM in striatum. These sites were unevenly distributed, representing different proportions of specific glutamate binding in different brain regions. The distribution of glutamate-binding sites correlated very well with the projection areas of putative glutamatergic pathways. This technique provides an extremely sensitive assay which can be used to gather detailed pharmacological and anatomical information about L-[3H]glutamate binding in the central nervous system

  7. ATP secretion from nerve trunks and Schwann cells mediated by glutamate.

    Science.gov (United States)

    Liu, Guo Jun; Bennett, Max R

    2003-11-14

    ATP release from rat sciatic nerves and from cultured Schwann cells isolated from the nerves was investigated using an online bioluminescence technique. ATP was released in relatively large amounts from rat sciatic nerve trunks during electrical stimulation. This release was blocked by the sodium channel inhibitor tetrodotoxin and the non-NMDA glutamate receptor blocker 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). Schwann cells isolated from the nerve trunks did not release ATP when electrically stimulated but did in response to glutamate in a concentration-dependent manner. Glutamate-stimulated ATP release was inhibited by specific non-competitive AMPA receptor antagonist GYKI 52466 and competitive non-NMDA receptor antagonist CNQX. Glutamate-stimulated ATP release was decreased by inhibition of anion transporter inhibitors by furosemide, cystic fibrosis transmembrane conductance regulator by glibenclamide and exocytosis by botulinum toxin A, indicating that anion transporters and exocytosis provide the main secretion mechanisms for ATP release from the Schwann cells.

  8. Relationship between glutamate dysfunction and symptoms and cognitive function in psychosis

    Directory of Open Access Journals (Sweden)

    Kate eMerritt

    2013-11-01

    Full Text Available The glutamate hypothesis of schizophrenia, proposed over two decades ago, originated following the observation that administration of drugs that block NMDA glutamate receptors, such as ketamine, could induce schizophrenia–like symptoms. Since then, this hypothesis has been extended to describe how glutamate abnormalities may disturb brain function and underpin psychotic symptoms and cognitive impairments. The glutamatergic system is now a major focus for the development of new compounds in schizophrenia. Relationships between regional brain glutamate function and symptom severity can be investigated using proton magnetic resonance spectroscopy (1H-MRS to estimate levels of glutamatergic metabolites in vivo. Here we briefly review the 1H-MRS studies that have explored relationships between glutamatergic metabolites, symptoms and cognitive function in clinical samples. While some of these studies suggest that more severe symptoms may be associated with elevated glutamatergic function in the anterior cingulate, studies in larger patient samples selected on the basis of symptom severity are required.

  9. Co-release of glutamate and GABA from single vesicles in GABAergic neurons exogenously expressing VGLUT3

    Directory of Open Access Journals (Sweden)

    Johannes eZimmermann

    2015-09-01

    Full Text Available The identity of the vesicle neurotransmitter transporter expressed by a neuron largely corresponds with the primary neurotransmitter that cell releases. However, the vesicular glutamate transporter subtype 3 (VGLUT3 is mainly expressed in non-glutamatergic neurons, including cholinergic, serotonergic, or GABAergic neurons. Though a functional role for glutamate release from these non-glutamatergic neurons has been demonstrated, the interplay between VGLUT3 and the neuron’s characteristic neurotransmitter transporter, particularly in the case of GABAergic neurons, at the synaptic and vesicular level is less clear. In this study, we explore how exogenous expression of VGLUT3 in striatal GABAergic neurons affects the packaging and release of glutamate and GABA in synaptic vesicles. We found that VGLUT3 expression in isolated, autaptic GABAergic neurons leads to action potential evoked release of glutamate. Under these conditions, glutamate and GABA could be packaged together in single vesicles release either spontaneously or asynchronously. However, the presence of glutamate in GABAergic vesicles did not affect uptake of GABA itself, suggesting a lack of synergy in vesicle filling for these transmitters. Finally, we found postsynaptic detection of glutamate released from GABAergic terminals difficult when bona fide glutamatergic synapses were present, suggesting that co-released glutamate cannot induce postsynaptic glutamate receptor clustering.

  10. 40 CFR 180.1187 - L-glutamic acid; exemption from the requirement of a tolerance.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 23 2010-07-01 2010-07-01 false L-glutamic acid; exemption from the... Exemptions From Tolerances § 180.1187 L-glutamic acid; exemption from the requirement of a tolerance. L-glutamic acid is exempt from the requirement of a tolerance on all food commodities when used in accordance...

  11. De-coupling of blood flow and metabolism in the rat brain induced by glutamate

    International Nuclear Information System (INIS)

    Hirose, Shinichiro; Momosaki, Sotaro; Sasaki, Kazunari; Hosoi, Rie; Abe, Kohji; Inoue, Osamu; Gee, A.

    2009-01-01

    Glutamate plays an essential role in neuronal cell death in many neurological disorders. In this study, we examined both glucose metabolism and cerebral blood flow in the same rat following infusion of glutamate or ibotenic acid using the dual-tracer technique. The effects of MK-801, an N-methyl-D-aspartate (NMDA) receptor antagonist, and 1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulfonamide (NBQX), an α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-kainate receptor antagonist, on the changes in the glucose metabolism and cerebral blood flow induced by glutamate were also examined. The rats were microinjected with glutamate (1 μmol/μl, 2 μl) or ibotenic acid (10 μg/μl, 1 μl) into the right striatum, and dual-tracer autoradiograms of [ 18 F]fluorodeoxyglucose (FDG) and [ 14 C]iofetamine (IMP) were obtained. MK-801 and NBQX were injected intravenously about 45 and 30 min, respectively, after the infusion of glutamate. De-coupling of blood flow and metabolism was noted in the glutamate-infused hemisphere (as assessed by no alteration of [ 18 F]FDG uptake and significant decrease of [ 14 C]IMP uptake). Pretreatments with MK-801, NBQX, or combined use of MK-801 and NBQX did not affect the de-coupling of the blood flow and metabolism induced by glutamate. A histochemical study revealed that about 20% neuronal cell death had occurred in the striatum at 105 min after the infusion of glutamate. In addition, a significant increase of the [ 18 F]FDG uptake and decrease of [ 14 C]IMP uptake were also seen in the rat brain infused with ibotenic acid. These results indicate that glutamate and ibotenic acid caused a significant de-coupling of blood flow and glucose metabolism in the intact rat brain during the early phase of neurodegeneration. It is necessary to evaluate the relation between metabotropic glutamate receptors and de-coupling of blood flow and metabolism. (author)

  12. Detection and quantitation of glutamate carboxypeptidase II in human blood

    Czech Academy of Sciences Publication Activity Database

    Knedlík, Tomáš; Navrátil, Václav; Vik, V.; Pacík, D.; Šácha, Pavel; Konvalinka, Jan

    2014-01-01

    Roč. 74, č. 7 (2014), s. 768-780 ISSN 0270-4137 R&D Projects: GA ČR GAP304/12/0847 Grant - others:OPPC(CZ) CZ.2.16/3.1.00/24016 Institutional support: RVO:61388963 Keywords : serum marker * glutamate carboxypeptidase II * plasma glutamate carboxypeptidase * prostate cancer * prostate -specific membrane antigen Subject RIV: CE - Biochemistry Impact factor: 3.565, year: 2014

  13. L-glutamate Receptor In Paramecium

    Science.gov (United States)

    Bernal-Martínez, Juan; Ortega-Soto, Arturo

    2004-09-01

    Behavioral, electrophysiological and biochemical experiments were performed in order to establish the presence of a glutamate receptor in the ciliate Paramecium. It was found that an AMPA/KA receptor is functionally expressed in Paramecium and that this receptor is immunologically and fillogenetically related to the AMPA/KA receptor present in vertebrates.

  14. Operation and maintenance techniques of pool and pool water purification system in IMEF

    Energy Technology Data Exchange (ETDEWEB)

    Soong, Woong Sup

    1999-03-01

    IMEF pool is used pass way between pool and hot cell in order to inlet and outlet of fuel pin in cask. All operation is performed conforming with naked eyes. Therefore floating matter is filtered so as to easy under water handling. Also radioactivity in pool water is controlled according to the nuclear law, radioactivity ration maintained less than 15mR/hr on pool side. Perfect operation and maintenance can be achieved well trained operator. Result obtained from the perfection can give more influence over restrain, spreading contamination of radioactivity materials. This report describes operation and maintenance technique of pool water purification system in IMEF. (Author). 7 refs., 13 figs.

  15. Operation and maintenance techniques of pool and pool water purification system in IMEF

    International Nuclear Information System (INIS)

    Soong, Woong Sup

    1999-03-01

    IMEF pool is used pass way between pool and hot cell in order to inlet and outlet of fuel pin in cask. All operation is performed conforming with naked eyes. Therefore floating matter is filtered so as to easy under water handling. Also radioactivity in pool water is controlled according to the nuclear law, radioactivity ration maintained less than 15mR/hr on pool side. Perfect operation and maintenance can be achieved well trained operator. Result obtained from the perfection can give more influence over restrain, spreading contamination of radioactivity materials. This report describes operation and maintenance technique of pool water purification system in IMEF. (Author). 7 refs., 13 figs

  16. The metabotropic glutamate receptors: structure, activation mechanism and pharmacology.

    Science.gov (United States)

    Pin, Jean-Philippe; Acher, Francine

    2002-06-01

    The metabotropic glutamate receptors are G-protein coupled receptors (GPCR) involved in the regulation of many synapses, including most glutamatergic fast excitatory synapses. Eight subtypes have been identified that can be classified into three groups. The molecular characterization of these receptors revealed proteins much more complex than any other GPCRs. They are composed of a Venus Flytrap (VFT) module where glutamate binds, connected to a heptahelical domain responsible for G-protein coupling. Recent data including the structure of the VFT module determined with and without glutamate, indicate that these receptors function as dimers. Moreover a number of intracellular proteins can regulate their targeting and transduction mechanism. Such structural features of mGlu receptors offer multiple possibilities for synthetic compounds to modulate their activity. In addition to agonists and competitive antagonists acting at the glutamate binding site, a number of non-competitive antagonists with inverse agonist activity, and positive allosteric modulators have been discovered. These later compounds share specific properties that make them good candidates for therapeutic applications. First, their non-amino acid structure makes them pass more easily the blood brain barrier. Second, they are much more selective than any other compound identified so far, being the first subtype selective molecules. Third, for the negative modulators, their non competitive mechanism of action makes them relatively unaffected by high concentrations of glutamate that may be present in disease states (e.g. stroke, epilepsy, neuropathic pain, etc.). Fourth, like the benzodiazepines acting at the GABA(A) receptors, the positive modulators offer a new way to increase the activity of these receptors in vivo, with a low risk of inducing their desensitization. The present review article focuses on the specific structural features of these receptors and highlights the various possibilities these

  17. Exposure to high glutamate concentration activates aerobic glycolysis but inhibits ATP-linked respiration in cultured cortical astrocytes.

    Science.gov (United States)

    Shen, Yao; Tian, Yueyang; Shi, Xiaojie; Yang, Jianbo; Ouyang, Li; Gao, Jieqiong; Lu, Jianxin

    2014-08-01

    Astrocytes play a key role in removing the synaptically released glutamate from the extracellular space and maintaining the glutamate below neurotoxic level in the brain. However, high concentration of glutamate leads to toxicity in astrocytes, and the underlying mechanisms are unclear. The purpose of this study was to investigate whether energy metabolism disorder, especially impairment of mitochondrial respiration, is involved in the glutamate-induced gliotoxicity. Exposure to 10-mM glutamate for 48 h stimulated glycolysis and respiration in astrocytes. However, the increased oxygen consumption was used for proton leak and non-mitochondrial respiration, but not for oxidative phosphorylation and ATP generation. When the exposure time extended to 72 h, glycolysis was still activated for ATP generation, but the mitochondrial ATP-linked respiration of astrocytes was reduced. The glutamate-induced astrocyte damage can be mimicked by the non-metabolized substrate d-aspartate but reversed by the non-selective glutamate transporter inhibitor TBOA. In addition, the glutamate toxicity can be partially reversed by vitamin E. These findings demonstrate that changes of bioenergetic profile occur in cultured cortical astrocytes exposed to high concentration of glutamate and highlight the role of mitochondria respiration in glutamate-induced gliotoxicity in cortical astrocytes. Copyright © 2014 John Wiley & Sons, Ltd.

  18. The structure and function of glutamate receptors: Mg2+ block to X-ray diffraction.

    Science.gov (United States)

    Mayer, Mark L

    2017-01-01

    Experiments on the action of glutamate on mammalian and amphibian nervous systems started back in the 1950s but decades passed before it became widely accepted that glutamate was the major excitatory neurotransmitter in the CNS. The pace of research greatly accelerated in the 1980s when selective ligands that identified glutamate receptor subtypes became widely available, and voltage clamp techniques, coupled with rapid perfusion, began to resolve the unique functional properties of what cloning subsequently revealed to be a large family of receptors with numerous subtypes. More recently the power of X-ray crystallography and cryo-EM has been applied to the study of glutamate receptors, revealing their atomic structures, and the conformational changes that underlie their gating. In this review I summarize the history of this field, viewed through the lens of a career in which I spent 3 decades working on the structure and function of glutamate receptor ion channels. This article is part of the Special Issue entitled 'Ionotropic glutamate receptors'. Published by Elsevier Ltd.

  19. Bioconversion of sugar cane molasses into glutamic acid by gamma irradiated corynebacterium glutamicum

    International Nuclear Information System (INIS)

    El-Batal, A.I.

    1996-01-01

    Corynebacterium glutamicum (ATCC 13058) was used for glutamic acid production from sugar cane molasses which contain sufficient. The addition of 5 units ml 4 of penicillin G was superior in glutamic acid production (11.5 g L 4 ). Tweens and their saturated fatty acids were effective on the accumulation of glutamic acid in the culture medium and the maximum yield (16.6 g L 4 ) was the addition of 5 mg ml 4 Tween 40. Gamma irradiation prior to Tween-40 treatment of bacterial cells resulted in an obvious increase in glutamic acid production and it was maximum (23.72 g L 4 ) at 0.1 k Gy exposure dose of inocula. 5 tabs

  20. Contribution of glutamate decarboxylase in Lactobacillus reuteri to acid resistance and persistence in sourdough fermentation.

    Science.gov (United States)

    Su, Marcia S; Schlicht, Sabine; Gänzle, Michael G

    2011-08-30

    Acid stress impacts the persistence of lactobacilli in industrial sourdough fermentations, and in intestinal ecosystems. However, the contribution of glutamate to acid resistance in lactobacilli has not been demonstrated experimentally, and evidence for the contribution of acid resistance to the competitiveness of lactobacilli in sourdough is lacking. It was therefore the aim of this study to investigate the ecological role of glutamate decarboxylase in L. reuteri. A gene coding for a putative glutamate decarboxylase, gadB, was identified in the genome of L. reuteri 100-23. Different from the organization of genetic loci coding for glutamate decarboxylase in other lactic acid bacteria, gadB was located adjacent to a putative glutaminase gene, gls3. An isogenic deletion mutant, L. reuteri ∆gadB, was generated by a double crossover method. L. reuteri 100-23 but not L. reuteri ∆gadB converted glutamate to γ-aminobutyrate (GABA) in phosphate butter (pH 2.5). In sourdough, both strains converted glutamine to glutamate but only L. reuteri 100-23 accumulated GABA. Glutamate addition to phosphate buffer, pH 2.5, improved survival of L. reuteri 100-23 100-fold. However, survival of L. reuteri ∆gadB remained essentially unchanged. The disruption of gadB did not affect growth of L. reuteri in mMRS or in sourdough. However, the wild type strain L. reuteri 100-23 displaced L. reuteri ∆gadB after 5 cycles of fermentation in back-slopped sourdough fermentations. The conversion of glutamate to GABA by L. reuteri 100-23 contributes to acid resistance and to competitiveness in industrial sourdough fermentations. The organization of the gene cluster for glutamate conversion, and the availability of amino acids in cereals imply that glutamine rather than glutamate functions as the substrate for GABA formation. The exceptional coupling of glutamine deamidation to glutamate decarboxylation in L. reuteri likely reflects adaptation to cereal substrates.

  1. Dual Effects of TARP γ-2 on Glutamate Efficacy Can Account for AMPA Receptor Autoinactivation

    Directory of Open Access Journals (Sweden)

    Ian D. Coombs

    2017-08-01

    Full Text Available Fast excitatory transmission in the CNS is mediated mainly by AMPA-type glutamate receptors (AMPARs associated with transmembrane AMPAR regulatory proteins (TARPs. At the high glutamate concentrations typically seen during synaptic transmission, TARPs slow receptor desensitization and enhance mean channel conductance. However, their influence on channels gated by low glutamate concentrations, as encountered during delayed transmitter clearance or synaptic spillover, is poorly understood. We report here that TARP γ-2 reduces the ability of low glutamate concentrations to cause AMPAR desensitization and enhances channel gating at low glutamate occupancy. Simulations show that, by shifting the balance between AMPAR activation and desensitization, TARPs can markedly facilitate the transduction of spillover-mediated synaptic signaling. Furthermore, the dual effects of TARPs can account for biphasic steady-state glutamate concentration-response curves—a phenomenon termed “autoinactivation,” previously thought to reflect desensitization-mediated AMPAR/TARP dissociation.

  2. Swimming pool granuloma

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/001357.htm Swimming pool granuloma To use the sharing features on this page, please enable JavaScript. A swimming pool granuloma is a long-term (chronic) skin ...

  3. A novel stereospecific synthesis of 14C labeled 1-glutamic acid

    International Nuclear Information System (INIS)

    Wurz, R.E.; Kepner, R.E.; Webb, A.D.

    1989-01-01

    A stereospecific synthesis of 4- 14 C-1-glutamic acid was completed in five steps from sodium 2- 14 C-acetate. The morpholine derived enamine of ethyl pyruvate was reacted with ethyl 2- 14 C-bromoacetate to give after hydrolysis diethyl 4- 14 C-2-oxoglutarate. The 2-oxoglutarate was reacted with hydroxylamine hydrochloride to give diethyl 4-14C-2-hydroxyiminoglutarate which was then reduced with a LiAlH4, (-)-N-methylephedrine and 3,5-dimethylphenol mixture to give 4- 14 C-1-glutamic acid. The 4- 14 C-1-glutamic acid was used in investigations into the biosynthesis of gamma-lactones in sherries

  4. Intercellular signal communication among odontoblasts and trigeminal ganglion neurons via glutamate.

    Science.gov (United States)

    Nishiyama, A; Sato, M; Kimura, M; Katakura, A; Tazaki, M; Shibukawa, Y

    2016-11-01

    Various stimuli to the exposed surface of dentin induce changes in the hydrodynamic force inside the dentinal tubules resulting in dentinal pain. Recent evidences indicate that mechano-sensor channels, such as the transient receptor potential channels, in odontoblasts receive these hydrodynamic forces and trigger the release of ATP to the pulpal neurons, to generate dentinal pain. A recent study, however, has shown that odontoblasts also express glutamate receptors (GluRs). This implies that cells in the dental pulp tissue have the ability to release glutamate, which acts as a functional intercellular mediator to establish inter-odontoblast and odontoblast-trigeminal ganglion (TG) neuron signal communication. To investigate the intercellular signal communication, we applied mechanical stimulation to odontoblasts and measured the intracellular free Ca 2+ concentration ([Ca 2+ ] i ). During mechanical stimulation in the presence of extracellular Ca 2+ , we observed a transient [Ca 2+ ] i increase not only in single stimulated odontoblasts, but also in adjacent odontoblasts. We could not observe these responses in the absence of extracellular Ca 2+ . [Ca 2+ ] i increases in the neighboring odontoblasts during mechanical stimulation of single odontoblasts were inhibited by antagonists of metabotropic glutamate receptors (mGluRs) as well as glutamate-permeable anion channels. In the odontoblast-TG neuron coculture, we observed an increase in [Ca 2+ ] i in the stimulated odontoblasts and TG neurons, in response to direct mechanical stimulation of single odontoblasts. These [Ca 2+ ] i increases in the neighboring TG neurons were inhibited by antagonists for mGluRs. The [Ca 2+ ] i increases in the stimulated odontoblasts were also inhibited by mGluRs antagonists. We further confirmed that the odontoblasts express group I, II, and III mGluRs. However, we could not record any currents evoked from odontoblasts near the mechanically stimulated odontoblast, with or without

  5. A Stable Glutamate Biosensor Based on MnO2 Bulk-modified ...

    African Journals Online (AJOL)

    An amperometric glutamate biosensor was developed using screen-printed carbon electrodes bulk-modified with MnO2 (5%, m:m) onto which glutamate oxidase was immobilized via Nafion(R) film entrapment. The analytical performance of the biosensor was assessed in a flow injection mode and peak heights of the ...

  6. Paraventricular Stimulation with Glutamate Elicits Bradycardia and Pituitary Responses

    Science.gov (United States)

    Darlington, Daniel N.; Miyamoto, Michael; Keil, Lanny C.; Dallman, Mary F.

    1989-01-01

    The excitatory neurotransmitter, L-glutamate (0.5 M, pH 7.4), or the organic acid, acetate (0.5 M, pH 7.4), was microinjected (50 nl over 2 min) directly into the paraventricular nuclei (PVN) of pentobarbital sodium-anesthetized rats while arterial blood pressure and heart rate and plasma adrenocorticotropic hormone (ACTH), vasopressin, and oxytocin were measured. Activation of PVN neurons with L-glutamate led to increases in plasma ACTH, vasopressin, and oxytocin and a profound bradycardia (-80 beats/min) with little change in arterial blood pressure. Microinjection of acetate had no effect on the above variables. The decrease in heart rate was shown to be dependent on the concentration of glutamate injected and the volume of injectate. The bradycardia was mediated through the autonomic nervous system because ganglionic blockade (pentolinium tartrate) eliminated the response; atropine and propranolol severely attenuated the bradycardia. The bradycardia was greatest when L-glutamate was microinjected into the caudal PVN. Injections into the rostral PVN or into nuclei surrounding the PVN led to small or nonsignificant decreases in heart rate. Focal electric stimulation (2-50 pA) of the PVN also led to decreases in heart rate and arterial blood pressure. These data suggest that activation of PVN neurons leads to the release of ACTH, vasopressin, and oxytocin from the pituitary and a bradycardia that is mediated by the autonomic nervous system.

  7. Detection of Glutamate and γ-aminobutyric Acid in Vitreous of Patients with Proliferative Diabetic Retinopathy

    Institute of Scientific and Technical Information of China (English)

    Juan Deng; De-Zheng Wu; Rulong Gao

    2000-01-01

    Purpose: To study the levels of glutamate and γ-aminobutyric acid (GABA) in vitreous of patients with proliferative diabetic retinopathy(PDR) and to investigate their roles in retinal ischemia.Method: Vitreous samples were collected from 25 patients (27 eyes) with PDR and 14patients ( 14 eyes) with idiopathic macular hole. Glutamate and GABA detection were performed by high-performance liquid chromatography (HPLC).Results: Patients with PDR had significantly higher concentrations of glutamate and GABA than the control group. The glutamate level has a significantly positive correlation with GABA level.Conclusion: Detection of glutamate and GABA in vitreous provides biochemical support for the mechanism and treatment of ischemic retinal damage in patients with PDR.

  8. New set of convective heat transfer coefficients established for pools and validated against CLARA experiments for application to corium pools

    Energy Technology Data Exchange (ETDEWEB)

    Michel, B., E-mail: benedicte.michel@irsn.fr

    2015-05-15

    Highlights: • A new set of 2D convective heat transfer correlations is proposed. • It takes into account different horizontal and lateral superficial velocities. • It is based on previously established correlations. • It is validated against recent CLARA experiments. • It has to be implemented in a 0D MCCI (molten core concrete interaction) code. - Abstract: During an hypothetical Pressurized Water Reactor (PWR) or Boiling Water Reactor (BWR) severe accident with core meltdown and vessel failure, corium would fall directly on the concrete reactor pit basemat if no water is present. The high temperature of the corium pool maintained by the residual power would lead to the erosion of the concrete walls and basemat of this reactor pit. The thermal decomposition of concrete will lead to the release of a significant amount of gases that will modify the corium pool thermal hydraulics. In particular, it will affect heat transfers between the corium pool and the concrete which determine the reactor pit ablation kinetics. A new set of convective heat transfer coefficients in a pool with different lateral and horizontal superficial gas velocities is modeled and validated against the recent CLARA experimental program. 155 tests of this program, in two size configurations and a high range of investigated viscosity, have been used to validate the model. Then, a method to define different lateral and horizontal superficial gas velocities in a 0D code is proposed together with a discussion about the possible viscosity in the reactor case when the pool is semi-solid. This model is going to be implemented in the 0D ASTEC/MEDICIS code in order to determine the impact of the convective heat transfer in the concrete ablation by corium.

  9. Seismic analysis and design of spent subassembly storage bay (SSSB) pool

    International Nuclear Information System (INIS)

    Abdul Gani, H.I.; Ramanjaneyulu, K.V.S.; Pillai, C.S.; Chetal, S.C.

    2003-01-01

    Fuel bundles, after their specified stay in reactor core, are replaced by fresh fuel for sustaining power generation at rated levels. The irradiated fuel subassembly, removed fresh from core, known as spent fuel sub assembly, is radioactive and decay heat generating. It needs to be cooled before it becomes amenable for handling, either for reprocessing or for immobilisation. For this purpose, it is immersed in a pool of water, retained in a concrete structure referred as Spent Subassembly Storage Bay (SSSB) pool. The height of water column above fuel bundles is arrived from shielding considerations. SSSB pool is one of the nuclear safety related structures and warrants rigorous analysis and design. The SSSB pool, in case of PFBR 500 MW(e) is located in fuel building. It is a stainless steel lined. water retaining rectangular R.C.C. open tank of size 7.5 X 29.0 m, with a height of 11.0 m. This structure is analysed for two levels of site specific earthquakes taking in to account liquid structure interactions as per ASCE-4, 1998. The design of walls and bottom slab is carried out satisfying the AERB code for nuclear safety related structures. Analysis and design of SSSB pool of PFBR is presented in the following paper. (author)

  10. Swimming pool hydraulics and their significance for public pools. Bedeutung der Beckenhydraulik in oeffentlichen Schwimmbaedern

    Energy Technology Data Exchange (ETDEWEB)

    Gansloser, G

    1989-11-01

    The term of swimming pool hydraulics means the process of letting in and drawing off water to and from the pool while ensuring that no inadmissible water-borne contaminant concentrations will occur anywhere within the pool. Measurements were performed on a pool to study the significance of correct pool hydraulics. The author points out that a wrong water recirculation design will bring to nought the effects of an elaborate water treatment system; by contrast, poor pool water quality can be greatly improved by redesigning the pool water hydraulics approach. In principle, systems with with water inlet at one side and water outlet at the far side will fall short of hygienic requirements. (BWI).

  11. Glutamic acid and folic acid production in aerobic and anaerobic probiotics

    Directory of Open Access Journals (Sweden)

    Zohre Taghi Abadi

    2018-03-01

    Full Text Available Introduction:From an industrial application or commercial point of view, glutamic acid is one of the most important amino acids and its microbial production has been reported from some bacteria. Regarding the role of probiotics to modulate human health and the ever-increasing demand of prebiotics in the food industry, in the current study, production of glutamic acid and folic acid from three probiotic bacteria (Bifidobacterium, Bifidobacterium bifidum, Sporolactobacillus was evaluated for the first time. Materials and methods: MRS broth and exclusive media was used for probiotic culture. The glutamic acid was identified using thin-layer chromatography and folic acid production was measured by folate kit. Each bacterium in terms of quality and quantity were measured by high pressure liquid chromatography. Results: Production of glutamic acid confirmed is based on the thin layer chromatography analysis and high pressure liquid chromatography results. In addition, it was observed that all three probiotics produce folic acid. The prevalence of folate in Bifidobacterium was measured as 315 mg/ml that was more than two other bacteria. Discussion and conclusion: To the best of our knowledge, this is the first report of microbial production of glutamic acid and folate from the probiotic bacteria. These beneficial bacteria can be used as a good source for mass production of these valuable compounds.

  12. Altered astrocyte glutamate transporter regulation of hypothalamic neurosecretory neurons in heart failure rats.

    Science.gov (United States)

    Potapenko, Evgeniy S; Biancardi, Vinicia C; Zhou, Yiqiang; Stern, Javier E

    2012-08-01

    Neurohumoral activation, which includes augmented plasma levels of the neurohormone vasopressin (VP), is a common finding in heart failure (HF) that contributes to morbidity and mortality in this disease. While an increased activation of magnocellular neurosecretory cells (MNCs) and enhanced glutamate function in HF is well documented, the precise underlying mechanisms remain to be elucidated. Here, we combined electrophysiology and protein measurements to determine whether altered glial glutamate transporter function and/or expression occurs in the hypothalamic supraoptic nucleus (SON) during HF. Patch-clamp recordings obtained from MNCs in brain slices show that pharmacological blockade of astrocyte glutamate transporter 1 (GLT1) function [500 μM dihydrokainate (DHK)], resulted in a persistent N-methyl-D-aspartate receptor (NMDAR)-mediated inward current (tonic I(NMDA)) in sham rats, an effect that was significantly smaller in MNCs from HF rats. In addition, we found a diminished GLT1 protein content in plasma membrane (but not cytosolic) fractions of SON punches in HF rats. Conversely, astrocyte GLAST expression was significantly higher in the SON of HF rats, while nonselective blockade of glutamate transport activity (100 μM TBOA) evoked an enhanced tonic I(NMDA) activation in HF rats. Steady-state activation of NMDARs by extracellular glutamate levels was diminished during HF. Taken together, these results support a shift in the relative expression and function of two major glial glutamate transporters (from GLT1 to GLAST predominance) during HF. This shift may act as a compensatory mechanism to preserve an adequate basal glutamate uptake level in the face of an enhanced glutamatergic afferent activity in HF rats.

  13. 13 CFR 120.1706 - Pool Originator's retained interest in Pool.

    Science.gov (United States)

    2010-01-01

    ... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Pool Originator's retained interest in Pool. 120.1706 Section 120.1706 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION BUSINESS LOANS Establishment of SBA Secondary Market Guarantee Program for First Lien Position 504 Loan...

  14. Depolarization-induced release of [(3)H]D-aspartate from GABAergic neurons caused by reversal of glutamate transporters

    DEFF Research Database (Denmark)

    Jensen, J B; Pickering, D S; Schousboe, A

    2000-01-01

    if glutamate in addition to gamma-aminobutyric acid (GABA) could be released from these cultures. The neurons were preloaded with [(3)H]D-aspartate and subsequently its release was followed during depolarization induced by a high potassium concentration or the alpha-amino-3-hydroxy-5-methyl-4......-isoxazolepropionic acid (AMPA) receptor agonists, AMPA and kainate. Depolarization of the neurons with 55 mM potassium increased the release of [(3)H]D-aspartate by more than 10-fold. When the non-specific calcium-channel blockers cobalt or lanthanum were included in the stimulation buffer with potassium......, the release of [(3)H]D-aspartate was decreased by about 40%. These results indicated that some of the released [(3)H]D-aspartate might originate from a vesicular pool. When AMPA was applied to the neurons, the release of [(3)H]D-aspartate was increased 2-fold and could not be prevented or decreased...

  15. Measurement of argon concentrations in a TRIGA Mark-III pool

    Energy Technology Data Exchange (ETDEWEB)

    Simms, R [California State University, Northridge, CA (United States)

    1974-07-01

    Argon-41, the principal radioactive effluent from a pool type reactor during normal operation, is produced by the {sup 40}A (n,{gamma}) reaction. The reactant, {sup 40}A, is introduced into the pool water by contact with the air. Reduction in radioactive argon release can be accomplished by reducing the concentration of dissolved {sup 40}A and retaining the {sup 41}A within the pool. However, little data were available concerning the mechanisms of argon introduction, production, retention, and release from a reactor pool. Experiments have therefore been performed at the Torrey Pines TRIGA Mark-III Reactor to develop techniques to sample dissolved argon and to provide data on argon concentrations in the pool for release modeling studies. Significant results for argon dissolved at different pool depths can only be obtained if the water samples are sealed at the point of collection. A special handling tool was developed to perform this remote operation. Pool samples were counted for {sup 41}A soon after collection with a NaI spectrometer. After allowing one day for decay of {sup 41}A, the concentration of {sup 40}A in the water sample was determined by neutron activation analysis. In each case, the 1.29 MeV gamma-ray peak of {sup 41}A was used. Interference from the 1.37 MeV {sup 24}Na peak was considered and its effect subtracted after determining {sup 24}Na content from the 2.75 MeV {sup 24}Na peak and a sodium standard. A Ge(Li) detector was tried and found to eliminate the problem, but it introduced an unacceptable geometrical effect dependent on bubble size within the sample bottles. Samples were taken from the 27 ft deep TRIGA pool at various locations. Results were obtained for samples taken on several different days along the same vertical line about 3-1/2 ft from the reactor centerline. Temperature measurements along this vertical traverse indicated a sharp temperature gradient at about 15 ft below the surface ({approx}6 ft above the top of the reactor). The

  16. Zinc and glutamate dehydrogenase in putative glutamatergic brain structures.

    Science.gov (United States)

    Wolf, G; Schmidt, W

    1983-01-01

    A certain topographic parallelism between the distribution of histochemically (TIMM staining) identified zinc and putative glutamatergic structures in the rat brain was demonstrated. Glutamate dehydrogenase as a zinc containing protein is in consideration to be an enzyme synthesizing transmitter glutamate. In a low concentration range externally added zinc ions (10(-9) to 10(-7) M) induced an increase in the activity of glutamate dehydrogenase (GDH) originating from rat hippocampal formation, neocortex, and cerebellum up to 142.4%. With rising molarity of Zn(II) in the incubation medium, the enzyme of hippocampal formation and cerebellum showed a biphasic course of activation. Zinc ions of a concentration higher than 10(-6) M caused a strong inhibition of GDH. The effect of Zn(II) on GDH originating from spinal ganglia and liver led only to a decrease of enzyme activity. These results are discussed in connection with a functional correlation between zinc and putatively glutamatergic system.

  17. Seismic loads in modularized and unmodularized large pools located on hard or intermediate hard sites

    Energy Technology Data Exchange (ETDEWEB)

    Dong, R G [California Univ., Livermore (USA). Lawrence Livermore Lab.

    1977-12-01

    To augment the present capacity of pools for storing spent nuclear fuel elements, pools larger than those in current use are being planned. These pools may or may not be modularized into cells. Because of the large size of the pools, seismic loads are of significant interest. In particular, the effects of modularization and site hardness are of concern. The study presented in this paper reveals that modularization is generally unfavourable, because it creates the option of leaving one or more cells empty which in turn results in higher structural loads. The wall which separates a filled cell from an empty cell, or the wall which bears against earth on one side and faces an empty cell on the other, becomes very highly stressed. For the particular pool geometries examined, a hard site is generally preferred over an intermediate hard site in terms of structural loads.

  18. The role of glutamate in neuronal ion homeostasis: A case study of spreading depolarization.

    Directory of Open Access Journals (Sweden)

    Niklas Hübel

    2017-10-01

    Full Text Available Simultaneous changes in ion concentrations, glutamate, and cell volume together with exchange of matter between cell network and vasculature are ubiquitous in numerous brain pathologies. A complete understanding of pathological conditions as well as normal brain function, therefore, hinges on elucidating the molecular and cellular pathways involved in these mostly interdependent variations. In this paper, we develop the first computational framework that combines the Hodgkin-Huxley type spiking dynamics, dynamic ion concentrations and glutamate homeostasis, neuronal and astroglial volume changes, and ion exchange with vasculature into a comprehensive model to elucidate the role of glutamate uptake in the dynamics of spreading depolarization (SD-the electrophysiological event underlying numerous pathologies including migraine, ischemic stroke, aneurysmal subarachnoid hemorrhage, intracerebral hematoma, and trauma. We are particularly interested in investigating the role of glutamate in the duration and termination of SD caused by K+ perfusion and oxygen-glucose deprivation. Our results demonstrate that glutamate signaling plays a key role in the dynamics of SD, and that impaired glutamate uptake leads to recovery failure of neurons from SD. We confirm predictions from our model experimentally by showing that inhibiting astrocytic glutamate uptake using TFB-TBOA nearly quadruples the duration of SD in layers 2-3 of visual cortical slices from juvenile rats. The model equations are either derived purely from first physical principles of electroneutrality, osmosis, and conservation of particles or a combination of these principles and known physiological facts. Accordingly, we claim that our approach can be used as a future guide to investigate the role of glutamate, ion concentrations, and dynamics cell volume in other brain pathologies and normal brain function.

  19. Chronic postnatal stress induces voluntary alcohol intake and modifies glutamate transporters in adolescent rats.

    Science.gov (United States)

    Odeon, María Mercedes; Andreu, Marcela; Yamauchi, Laura; Grosman, Mauricio; Acosta, Gabriela Beatriz

    2015-01-01

    Postnatal stress alters stress responses for life, with serious consequences on the central nervous system (CNS), involving glutamatergic neurotransmission and development of voluntary alcohol intake. Several drugs of abuse, including alcohol and cocaine, alter glutamate transport (GluT). Here, we evaluated effects of chronic postnatal stress (CPS) on alcohol intake and brain glutamate uptake and transporters in male adolescent Wistar rats. For CPS from postnatal day (PD) 7, pups were separated from their mothers and exposed to cold stress (4 °C) for 1 h daily for 20 days; controls remained with their mothers. Then they were exposed to either voluntary ethanol (6%) or dextrose (1%) intake for 7 days (5-7 rats per group), then killed. CPS: (1) increased voluntary ethanol intake, (2) did not affect body weight gain or produce signs of toxicity with alcohol exposure, (3) increased glutamate uptake by hippocampal synaptosomes in vitro and (4) reduced protein levels (Western measurements) in hippocampus and frontal cortex of glial glutamate transporter-1 (GLT-1) and excitatory amino-acid transporter-3 (EAAT-3) but increased glutamate aspartate transporter (GLAST) levels. We propose that CPS-induced decrements in GLT-1 and EAAT-3 expression levels are opposed by activation of a compensatory mechanism to prevent excitotoxicity. A greater role for GLAST in total glutamate uptake to prevent enlarged extracellular glutamate levels is inferred. Although CPS strongly increased intake of ethanol, this had little impact on effects of CPS on brain glutamate uptake or transporters. However, the impact of early life adverse events on glutamatergic neurotransmission may underlie increased alcohol consumption in adulthood.

  20. The role of glutamate in neuronal ion homeostasis: A case study of spreading depolarization.

    Science.gov (United States)

    Hübel, Niklas; Hosseini-Zare, Mahshid S; Žiburkus, Jokūbas; Ullah, Ghanim

    2017-10-01

    Simultaneous changes in ion concentrations, glutamate, and cell volume together with exchange of matter between cell network and vasculature are ubiquitous in numerous brain pathologies. A complete understanding of pathological conditions as well as normal brain function, therefore, hinges on elucidating the molecular and cellular pathways involved in these mostly interdependent variations. In this paper, we develop the first computational framework that combines the Hodgkin-Huxley type spiking dynamics, dynamic ion concentrations and glutamate homeostasis, neuronal and astroglial volume changes, and ion exchange with vasculature into a comprehensive model to elucidate the role of glutamate uptake in the dynamics of spreading depolarization (SD)-the electrophysiological event underlying numerous pathologies including migraine, ischemic stroke, aneurysmal subarachnoid hemorrhage, intracerebral hematoma, and trauma. We are particularly interested in investigating the role of glutamate in the duration and termination of SD caused by K+ perfusion and oxygen-glucose deprivation. Our results demonstrate that glutamate signaling plays a key role in the dynamics of SD, and that impaired glutamate uptake leads to recovery failure of neurons from SD. We confirm predictions from our model experimentally by showing that inhibiting astrocytic glutamate uptake using TFB-TBOA nearly quadruples the duration of SD in layers 2-3 of visual cortical slices from juvenile rats. The model equations are either derived purely from first physical principles of electroneutrality, osmosis, and conservation of particles or a combination of these principles and known physiological facts. Accordingly, we claim that our approach can be used as a future guide to investigate the role of glutamate, ion concentrations, and dynamics cell volume in other brain pathologies and normal brain function.

  1. A Detailed Model of Electroenzymatic Glutamate Biosensors To Aid in Sensor Optimization and in Applications in Vivo.

    Science.gov (United States)

    Clay, Mackenzie; Monbouquette, Harold G

    2018-02-21

    Simulations conducted with a detailed model of glutamate biosensor performance describe the observed sensor performance well, illustrate the limits of sensor performance, and suggest a path toward sensor optimization. Glutamate is the most important excitatory neurotransmitter in the brain, and electroenzymatic sensors have emerged as a useful tool for the monitoring of glutamate signaling in vivo. However, the utility of these sensors currently is limited by their sensitivity and response time. A mathematical model of a typical glutamate biosensor consisting of a Pt electrode coated with a permselective polymer film and a top layer of cross-linked glutamate oxidase has been constructed in terms of differential material balances on glutamate, H 2 O 2 , and O 2 in one spatial dimension. Simulations suggest that reducing thicknesses of the permselective polymer and enzyme layers can increase sensitivity ∼6-fold and reduce response time ∼7-fold, and thereby improve resolution of transient glutamate signals. At currently employed enzyme layer thicknesses, both intrinsic enzyme kinetics and enzyme deactivation likely are masked by mass transfer. However, O 2 -dependence studies show essentially no reduction in signal at the lowest anticipated O 2 concentrations for expected glutamate concentrations in the brain and that O 2 transport limitations in vitro are anticipated only at glutamate concentrations in the mM range. Finally, the limitations of current biosensors in monitoring glutamate transients is simulated and used to illustrate the need for optimized biosensors to report glutamate signaling accurately on a subsecond time scale. This work demonstrates how a detailed model can be used to guide optimization of electroenzymatic sensors similar to that for glutamate and to ensure appropriate interpretation of data gathered using such biosensors.

  2. Anions mediate ligand binding in Adineta vaga glutamate receptor ion channels.

    Science.gov (United States)

    Lomash, Suvendu; Chittori, Sagar; Brown, Patrick; Mayer, Mark L

    2013-03-05

    AvGluR1, a glutamate receptor ion channel from the primitive eukaryote Adineta vaga, is activated by alanine, cysteine, methionine, and phenylalanine, which produce lectin-sensitive desensitizing responses like those to glutamate, aspartate, and serine. AvGluR1 LBD crystal structures reveal an unusual scheme for binding dissimilar ligands that may be utilized by distantly related odorant/chemosensory receptors. Arginine residues in domain 2 coordinate the γ-carboxyl group of glutamate, whereas in the alanine, methionine, and serine complexes a chloride ion acts as a surrogate ligand, replacing the γ-carboxyl group. Removal of Cl(-) lowers affinity for these ligands but not for glutamate or aspartate nor for phenylalanine, which occludes the anion binding site and binds with low affinity. AvGluR1 LBD crystal structures and sedimentation analysis also provide insights into the evolutionary link between prokaryotic and eukaryotic iGluRs and reveal features unique to both classes, emphasizing the need for additional structure-based studies on iGluR-ligand interactions. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. In Vivo Measurements of Glutamate, GABA, and NAAG in Schizophrenia

    OpenAIRE

    Rowland, Laura M.; Kontson, Kimberly; West, Jeffrey; Edden, Richard A.; Zhu, He; Wijtenburg, S. Andrea; Holcomb, Henry H.; Barker, Peter B.

    2012-01-01

    The major excitatory and inhibitory neurotransmitters, glutamate (Glu) and gamma-aminobutyric acid (GABA), respectively, are implicated in the pathophysiology of schizophrenia. N-acetyl-aspartyl-glutamate (NAAG), a neuropeptide that modulates the Glu system, may also be altered in schizophrenia. This study investigated GABA, Glu + glutamine (Glx), and NAAG levels in younger and older subjects with schizophrenia. Forty-one subjects, 21 with chronic schizophrenia and 20 healthy controls, partic...

  4. Biochemical characterization of an autoradiographic method for studying excitatory amino acid receptors using L-[3H]glutamate

    International Nuclear Information System (INIS)

    Cincotta, M.; Summers, R.J.; Beart, P.M.

    1989-01-01

    A method was developed for radiolabeling excitatory amino acid receptors of rat brain with L-[ 3 H]glutamate. Effective labeling of glutamate receptors in slide-mounted 10-microns sections was obtained using a low incubation volume (0.15 ml) and rapid washing: a procedure where high ligand concentrations were achieved with minimal waste. Saturation experiments using [ 3 H]glutamate revealed a single binding site of micromolar affinity. The Bmax was trebled in the presence of Ca2+ (2.5 mM) and Cl- (20 mM) with no change in the Kd. Binding was rapid, saturable, stereospecific, and sensitive to glutamate receptor agonists. The proportions of [ 3 H]glutamate binding sensitive to N-methyl-D-aspartate (NMDA), kainate, and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) were 34, 54, and 51%, respectively. NMDA inhibited binding at a distinct subset of L-[ 3 H]glutamate sites, whereas AMPA and kainate competed for some common sites. Labeling of sections with L-[ 3 H]glutamate in the presence of the selective agonists allowed autoradiographic visualization of glutamate receptor subtypes in brain tissue

  5. Biobased synthesis of acrylonitrile from glutamic acid

    NARCIS (Netherlands)

    Notre, le J.E.L.; Scott, E.L.; Franssen, M.C.R.; Sanders, J.P.M.

    2011-01-01

    Glutamic acid was transformed into acrylonitrile in a two step procedure involving an oxidative decarboxylation in water to 3-cyanopropanoic acid followed by a decarbonylation-elimination reaction using a palladium catalyst

  6. Molecular basis for convergent evolution of glutamate recognition by pentameric ligand-gated ion channels

    DEFF Research Database (Denmark)

    Lynagh, Timothy; Beech, Robin N.; Lalande, Maryline J.

    2015-01-01

    that glutamate recognition requires an arginine residue in the base of the binding site, which originated at least three distinct times according to phylogenetic analysis. Most remarkably, the arginine emerged on the principal face of the binding site in the Lophotrochozoan lineage, but 65 amino acids upstream......Glutamate is an indispensable neurotransmitter, triggering postsynaptic signals upon recognition by postsynaptic receptors. We questioned the phylogenetic position and the molecular details of when and where glutamate recognition arose in the glutamate-gated chloride channels. Experiments revealed......, on the complementary face, in the Ecdysozoan lineage. This combined experimental and computational approach throws new light on the evolution of synaptic signalling....

  7. Glutamate/glutamine metabolism coupling between astrocytes and glioma cells: neuroprotection and inhibition of glioma growth.

    Science.gov (United States)

    Yao, Pei-Sen; Kang, De-Zhi; Lin, Ru-Ying; Ye, Bing; Wang, Wei; Ye, Zu-Cheng

    2014-07-18

    Glioma glutamate release has been shown to promote the growth of glioma cells and induce neuronal injuries from epilepsy to neuronal death. However, potential counteractions from normal astrocytes against glioma glutamate release have not been fully evaluated. In this study, we investigated the glutamate/glutamine cycling between glioma cells and astrocytes and their impact on neuronal function. Co-cultures of glioma cells with astrocytes (CGA) in direct contact were established under different mix ratio of astrocyte/glioma. Culture medium conditioned in these CGAs were sampled for HPLC measurement, for neuronal ratiometric calcium imaging, and for neuronal survival assay. We found: (1) High levels of glutaminase expression in glioma cells, but not in astrocytes, glutaminase enables glioma cells to release large amount of glutamate in the presence of glutamine. (2) Glutamate levels in CGAs were directly determined by the astrocyte/glioma ratios, indicating a balance between glioma glutamate release and astrocyte glutamate uptake. (3) Culture media from CGAs of higher glioma/astrocyte ratios induced stronger neuronal Ca(2+) response and more severe neuronal death. (4) Co-culturing with astrocytes significantly reduced the growth rate of glioma cells. These results indicate that normal astrocytes in the brain play pivotal roles in glioma growth inhibition and in reducing neuronal injuries from glioma glutamate release. However, as tumor growth, the protective role of astrocytes gradually succumb to glioma cells. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Acacetin inhibits glutamate release and prevents kainic acid-induced neurotoxicity in rats.

    Directory of Open Access Journals (Sweden)

    Tzu-Yu Lin

    Full Text Available An excessive release of glutamate is considered to be a molecular mechanism associated with several neurological diseases that causes neuronal damage. Therefore, searching for compounds that reduce glutamate neurotoxicity is necessary. In this study, the possibility that the natural flavone acacetin derived from the traditional Chinese medicine Clerodendrum inerme (L. Gaertn is a neuroprotective agent was investigated. The effect of acacetin on endogenous glutamate release in rat hippocampal nerve terminals (synaptosomes was also investigated. The results indicated that acacetin inhibited depolarization-evoked glutamate release and cytosolic free Ca(2+ concentration ([Ca(2+]C in the hippocampal nerve terminals. However, acacetin did not alter synaptosomal membrane potential. Furthermore, the inhibitory effect of acacetin on evoked glutamate release was prevented by the Cav2.2 (N-type and Cav2.1 (P/Q-type channel blocker known as ω-conotoxin MVIIC. In a kainic acid (KA rat model, an animal model used for excitotoxic neurodegeneration experiments, acacetin (10 or 50 mg/kg was administrated intraperitoneally to the rats 30 min before the KA (15 mg/kg intraperitoneal injection, and subsequently induced the attenuation of KA-induced neuronal cell death and microglia activation in the CA3 region of the hippocampus. The present study demonstrates that the natural compound, acacetin, inhibits glutamate release from hippocampal synaptosomes by attenuating voltage-dependent Ca(2+ entry and effectively prevents KA-induced in vivo excitotoxicity. Collectively, these data suggest that acacetin has the therapeutic potential for treating neurological diseases associated with excitotoxicity.

  9. Isotopomer profiling of Leishmania mexicana promastigotes reveals important roles for succinate fermentation and aspartate uptake in tricarboxylic acid cycle (TCA) anaplerosis, glutamate synthesis, and growth.

    Science.gov (United States)

    Saunders, Eleanor C; Ng, William W; Chambers, Jennifer M; Ng, Milica; Naderer, Thomas; Krömer, Jens O; Likic, Vladimir A; McConville, Malcolm J

    2011-08-05

    Leishmania parasites proliferate within nutritionally complex niches in their sandfly vector and mammalian hosts. However, the extent to which these parasites utilize different carbon sources remains poorly defined. In this study, we have followed the incorporation of various (13)C-labeled carbon sources into the intracellular and secreted metabolites of Leishmania mexicana promastigotes using gas chromatography-mass spectrometry and (13)C NMR. [U-(13)C]Glucose was rapidly incorporated into intermediates in glycolysis, the pentose phosphate pathway, and the cytoplasmic carbohydrate reserve material, mannogen. Enzymes involved in the upper glycolytic pathway are sequestered within glycosomes, and the ATP and NAD(+) consumed by these reactions were primarily regenerated by the fermentation of phosphoenolpyruvate to succinate (glycosomal succinate fermentation). The initiating enzyme in this pathway, phosphoenolpyruvate carboxykinase, was exclusively localized to the glycosome. Although some of the glycosomal succinate was secreted, most of the C4 dicarboxylic acids generated during succinate fermentation were further catabolized in the TCA cycle. A high rate of TCA cycle anaplerosis was further suggested by measurement of [U-(13)C]aspartate and [U-(13)C]alanine uptake and catabolism. TCA cycle anaplerosis is apparently needed to sustain glutamate production under standard culture conditions. Specifically, inhibition of mitochondrial aconitase with sodium fluoroacetate resulted in the rapid depletion of intracellular glutamate pools and growth arrest. Addition of high concentrations of exogenous glutamate alleviated this growth arrest. These findings suggest that glycosomal and mitochondrial metabolism in Leishmania promastigotes is tightly coupled and that, in contrast to the situation in some other trypanosomatid parasites, the TCA cycle has crucial anabolic functions.

  10. Theoretical assessment of particle generation from sodium pool fires

    Energy Technology Data Exchange (ETDEWEB)

    Garcia, M., E-mail: monica.gmartin@ciemat.es [CIEMAT, Unit of Nuclear Safety Research, Av. Complutense, 40, 28040 Madrid (Spain); Herranz, L.E., E-mail: luisen.herranz@ciemat.es [CIEMAT, Unit of Nuclear Safety Research, Av. Complutense, 40, 28040 Madrid (Spain); Kissane, M.P., E-mail: Martin.KISSANE@oecd.org [Nuclear Safety Technology and Regulation Division, OECD Nuclear Energy Agency (NEA), 46 quai Alphonse Le Gallo, 92100 Boulogne-Billancourt (France)

    2016-12-15

    Highlights: • Development of particle generation model for sodium-oxides aerosol formation. • Development of partially validated numerical simulations to build up maps of saturation ratio. • Nucleation of supersaturated vapours as relevant source of aerosols over sodium pools. • Prediction of high concentrations of primary particles in the combustion zone. - Abstract: Potential sodium discharge in the containment during postulated Beyond Design Basis Accidents (BDBAs) in Sodium-cooled Fast Reactors (SFRs) would have major consequences for accident development in terms of energetics and source term. In the containment, sodium vaporization and subsequent oxidation would result in supersaturated oxide vapours that would undergo rapid nucleation creating toxic aerosols. Therefore, modelling this vapour nucleation is essential to proper source term assessment in SFRs. In the frame of the EU-JASMIN project, a particle generation model to calculate the particle generation rate and their primary size during an in-containment sodium pool fire has been developed. Based on a suite of individual models for sodium vaporization, oxygen natural circulation (3D modelling), sodium-oxygen chemical reactions, sodium-oxides-vapour nucleation and condensation, its consistency has been partially validated by comparing with available experimental data. As an outcome, large temperature and vapour concentration gradients set over the sodium pool have been found which result in large particle concentrations in the close vicinity of the pool.

  11. Maintenance of an obstruction-forced pool in a gravel-bed channel: streamflow, channel morphology, and sediment transport.

    Science.gov (United States)

    Richard D. Woodsmith; Marwan A. Hassan

    2005-01-01

    Maintenance of pool morphology in a stream channel with a mobile bed requires hydraulic conditions at moderate to high flows that route bed load through the pool as it is delivered from upstream. Through field measurements of discharge, vertical velocity profiles, bed load transport, and streambed scour, fill, and grain-size distribution, we found that maintenance of a...

  12. A Glio-Protective Role of mir-263a by Tuning Sensitivity to Glutamate

    DEFF Research Database (Denmark)

    Aw, Sherry Shiying; Lim, Isaac Kok Hwee; Tang, Melissa Xue Mei

    2017-01-01

    of CG5621/Grik, Nmdar1, and Nmdar2. mir-263a mutants exhibit excitotoxic death of a subset of astrocyte-like and ensheathing glia in the CNS. Glial-specific normalization of glutamate receptor levels restores cell numbers and suppresses the movement defect. Therefore, microRNA-mediated regulation...... of glutamate receptor levels protects glia from excitotoxicity, ensuring CNS health. Chronic low-level glutamate receptor overexpression due to mutations affecting microRNA (miRNA) regulation might contribute to glial dysfunction and CNS impairment....

  13. A Glutamate Homeostat Controls the Presynaptic Inhibition of Neurotransmitter Release

    Directory of Open Access Journals (Sweden)

    Xiling Li

    2018-05-01

    Full Text Available Summary: We have interrogated the synaptic dialog that enables the bi-directional, homeostatic control of presynaptic efficacy at the glutamatergic Drosophila neuromuscular junction (NMJ. We find that homeostatic depression and potentiation use disparate genetic, induction, and expression mechanisms. Specifically, homeostatic potentiation is achieved through reduced CaMKII activity postsynaptically and increased abundance of active zone material presynaptically at one of the two neuronal subtypes innervating the NMJ, while homeostatic depression occurs without alterations in CaMKII activity and is expressed at both neuronal subtypes. Furthermore, homeostatic depression is only induced through excess presynaptic glutamate release and operates with disregard to the postsynaptic response. We propose that two independent homeostats modulate presynaptic efficacy at the Drosophila NMJ: one is an intercellular signaling system that potentiates synaptic strength following diminished postsynaptic excitability, while the other adaptively modulates presynaptic glutamate release through an autocrine mechanism without feedback from the postsynaptic compartment. : Homeostatic mechanisms stabilize synaptic strength, but the signaling systems remain enigmatic. Li et al. suggest the existence of a homeostat operating at the Drosophila neuromuscular junction that responds to excess glutamate through an autocrine mechanism to adaptively inhibit presynaptic neurotransmitter release. This system parallels forms of plasticity at central synapses. Keywords: homeostatic synaptic plasticity, glutamate homeostasis, synaptic depression, Drosophila neuromuscular junction

  14. Aspects of dopamine and acetylcholine release induced by glutamate receptors

    International Nuclear Information System (INIS)

    Paes, Paulo Cesar de Arruda

    2002-01-01

    The basal ganglia play an important role in the motor control of rats and humans. This control involves different neurotransmitters and the mutual control of these key elements has been subject to several studies. In this work we determined the role of glutamate on the release of radioactively labelled dopamine and acetylcholine from chopped striatal tissue in vitro. The values of Effective Concentration 50% for glutamate, NMDA, kainic, quisqualic acids and AMPA on the release of dopamine and acetylcholine were obtained. The inhibitory effects of magnesium, tetrodotoxin, MK-801, AP5 and MCPG, as well as the effects of glycin were evaluated. The results suggested that dopamine is influenced by the NMDA type glutamate receptor while acetylcholine seems to be influenced by NMDA, kainate and AMPA receptors. Tetrodotoxin experiments suggested that kainate receptors are both present in cholinergic terminals and cell bodies while AMPA and NMDA receptors are preferentially distributed in cell bodies. Magnesium effectively blocked the NMDA stimulation and unexpectedly also AMPA- and quisqualate-induced acetylcholine release. The latter could not be blocked by MCPG ruling out the participation of methabotropic receptors. MK-801 also blocked NMDA-receptors. Results point out the importance of the glutamic acid control of dopamine and acetylcholine release in striatal tissue. (author)

  15. Modulation of [3H]-glutamate binding by serotonin in the rat hippocampus: An autoradiographic study

    International Nuclear Information System (INIS)

    Mennini, T.; Miari, A.

    1991-01-01

    Serotonin (5-HT) added in vitro increased [ 3 H]-glutamate specific binding in the rat hippocampus, reaching statistical significance in layers rich in N-Methyl-D-Aspartate sensitive glutamate receptors. This effect was explained by a significant increase in the apparent affinity of [ 3 H]-glutamate when 5-HT is added in vitro. Two days after lesion of serotonergic afferents to the hippocampus with 5,7- Dihydroxytryptamine [ 3 H]-glutamate binding was significantly decreased in the CA3 region and stratum lacunosum moleculare of the hippocampus, this reduction being reversed by in vitro addition of 10 μM 5-HT. The decrease observed is due to a significant reduction of quisqualate-insensitive (radiatum CA3) and kainate receptors (strata oriens, radiatum, pyramidal of CA3). Five days after lesion [ 3 H]-glutamate binding increased significantly in the CA3 region of the hippocampus but was not different from sham animals in the other hippocampal layers. Two weeks after lesion [ 3 H]-glutamate binding to quisqualate-insensitive receptors was increased in all the hippocampal layers, while kainate and quisqualate-sensitive receptors were not affected. These data are consistent with the possibility that 5-HT is a direct positive modulator of glutamate receptor subtypes

  16. Relationship between glutamate, GOT and GPT levels in maternal and fetal blood: a potential mechanism for fetal neuroprotection.

    Science.gov (United States)

    Zlotnik, Alexander; Tsesis, Svetlana; Gruenbaum, Benjamin Fredrick; Ohayon, Sharon; Gruenbaum, Shaun Evan; Boyko, Matthew; Sheiner, Eyal; Brotfain, Evgeny; Shapira, Yoram; Teichberg, Vivian Itzhak

    2012-09-01

    Excess glutamate in the brain is thought to be implicated in the pathophysiology of fetal anoxic brain injury, yet little is known about the mechanisms by which glutamate is regulated in the fetal brain. This study examines whether there are differences between maternal and fetal glutamate concentrations, and whether a correlation between them exists. 10 ml of venous blood was extracted from 87 full-term (>37 weeks gestation) pregnant women in active labor. Immediately after delivery of the neonate, 10 ml of blood from the umbilical artery and vein was extracted. Samples were analyzed for levels of glutamate, glutamate-oxaloacetate transaminase (GOT), and glutamate pyruvate transaminase (GPT). Fetal blood glutamate concentrations in both the umbilical artery and vein were found to be significantly higher than maternal blood (pGOT levels in the umbilical artery and vein were found to be significantly higher than maternal GOT levels (pGOT or GPT between the umbilical artery and vein. There was an association observed between glutamate levels in maternal blood and glutamate levels in both venous (R=0.32, pGOT, but not GPT levels. An association was observed between maternal and fetal blood glutamate levels. Copyright © 2012 Elsevier Ltd. All rights reserved.

  17. Talent Management - Case Study on Determining the Collective Pool of Talent

    Directory of Open Access Journals (Sweden)

    Mirabela-Constanta MATEI

    2012-11-01

    Full Text Available Our paper focuses on the importance of attracting and retaining talent in a company. Attracting talent refers not only to the selection of talented employees from outside the company, but also to their identification among existing employees by determining and developing the collective pool of talent. The aim of our paper is to get a better view on how companies understand, attract and retain talent. To achieve this aim, we first reviewed the literature in the field of interest and then conducted a case study on determining the collective pool of talent within a medium size company from Bihor County. Results are discussed.

  18. Replication of the Shrimp Virus WSSV Depends on Glutamate-Driven Anaplerosis.

    Directory of Open Access Journals (Sweden)

    Chun-Yuan Li

    Full Text Available Infection with the white spot syndrome virus (WSSV induces a metabolic shift in shrimp that resembles the "Warburg effect" in mammalian cells. This effect is triggered via activation of the PI3K-Akt-mTOR pathway, and it is usually accompanied by the activation of other metabolic pathways that provide energy and direct the flow of carbon and nitrogen. Here we show that unlike the glutamine metabolism (glutaminolysis seen in most cancer cells to double deaminate glutamine to produce glutamate and the TCA cycle intermediate α-ketoglutarate (α-KG, at the WSSV genome replication stage (12 hpi, although glutaminase (GLS expression was upregulated, only glutamate was taken up by the hemocytes of WSSV-infected shrimp. At the same time, we observed an increase in the activity of the two enzymes that convert glutamate to α-KG, glutamate dehydrogenase (GDH and aspartate aminotransferase (ASAT. α-ketoglutarate concentration was also increased. A series of inhibition experiments suggested that the up-regulation of GDH is regulated by mTORC2, and that the PI3K-mTORC1 pathway is not involved. Suppression of GDH and ASAT by dsRNA silencing showed that both of these enzymes are important for WSSV replication. In GDH-silenced shrimp, direct replenishment of α-KG rescued both ATP production and WSSV replication. From these results, we propose a model of glutamate-driven anaplerosis that fuels the TCA cycle via α-KG and ultimately supports WSSV replication.

  19. NblA1/A2-Dependent Homeostasis of Amino Acid Pools during Nitrogen Starvation in Synechocystis sp. PCC 6803.

    Science.gov (United States)

    Kiyota, Hiroshi; Hirai, Masami Yokota; Ikeuchi, Masahiko

    2014-06-30

    Nutrient balance is important for photosynthetic growth and biomass production in microalgae. Here, we investigated and compared metabolic responses of amino acid pools to nitrogen and sulfur starvation in a unicellular model cyanobacterium, Synechocystis sp. PCC 6803, and its mutant nblA1/A2. It is known that NblA1/A2-dependent and -independent breakdown of abundant photosynthetic phycobiliproteins and other cellular proteins supply nutrients to the organism. However, the contribution of the NblA1/A2-dependent nutrient supply to amino acid pool homeostasis has not been studied. Our study demonstrates that changes in the pool size of many amino acids during nitrogen starvation can be categorized as NblA1/A2-dependent (Gln, Glu, glutathione, Gly, Ile, Leu, Met, Phe, Pro, Ser, Thr, Tyr and Val) and NblA1/A2-independent (Ala, Asn, Lys, and Trp). We also report unique changes in amino acid pool sizes during sulfur starvation in wild type and the mutant and found a generally marked increase in the Lys pool in cyanobacteria during nutrient starvation. In conclusion, the NblA1/A2-dependent protein turnover contributes to the maintenance of many amino acid pools during nitrogen starvation.

  20. NblA1/A2-Dependent Homeostasis of Amino Acid Pools during Nitrogen Starvation in Synechocystis sp. PCC 6803

    Directory of Open Access Journals (Sweden)

    Hiroshi Kiyota

    2014-06-01

    Full Text Available Nutrient balance is important for photosynthetic growth and biomass production in microalgae. Here, we investigated and compared metabolic responses of amino acid pools to nitrogen and sulfur starvation in a unicellular model cyanobacterium, Synechocystis sp. PCC 6803, and its mutant nblA1/A2. It is known that NblA1/A2-dependent and -independent breakdown of abundant photosynthetic phycobiliproteins and other cellular proteins supply nutrients to the organism. However, the contribution of the NblA1/A2-dependent nutrient supply to amino acid pool homeostasis has not been studied. Our study demonstrates that changes in the pool size of many amino acids during nitrogen starvation can be categorized as NblA1/A2-dependent (Gln, Glu, glutathione, Gly, Ile, Leu, Met, Phe, Pro, Ser, Thr, Tyr and Val and NblA1/A2-independent (Ala, Asn, Lys, and Trp. We also report unique changes in amino acid pool sizes during sulfur starvation in wild type and the mutant and found a generally marked increase in the Lys pool in cyanobacteria during nutrient starvation. In conclusion, the NblA1/A2-dependent protein turnover contributes to the maintenance of many amino acid pools during nitrogen starvation.

  1. Evidence that L-glutamate can act as an exogenous signal to modulate root growth and branching in Arabidopsis thaliana.

    Science.gov (United States)

    Walch-Liu, Pia; Liu, Lai-Hua; Remans, Tony; Tester, Mark; Forde, Brian G

    2006-08-01

    The roots of many plant species are known to use inorganic nitrogen, in the form of , as a cue to initiate localized root proliferation within nutrient-rich patches of soil. We report here that, at micromolar concentrations and in a genotype-dependent manner, exogenous l-glutamate is also able to elicit complex changes in Arabidopsis root development. l-Glutamate is perceived specifically at the primary root tip and inhibits mitotic activity in the root apical meristem, but does not interfere with lateral root initiation or outgrowth. Only some time after emergence do lateral roots acquire l-glutamate sensitivity, indicating that their ability to respond to l-glutamate is developmentally regulated. Comparisons between different Arabidopsis ecotypes revealed a remarkable degree of natural variation in l-glutamate sensitivity, with C24 being the most sensitive. The aux1-7 auxin transport mutant had reduced l-glutamate sensitivity, suggesting a possible interaction between l-glutamate and auxin signaling. Surprisingly, two loss-of-function mutants at the AXR1 locus (axr1-3 and axr1-12) were hypersensitive to l-glutamate. A pharmacological approach, using agonists and antagonists of mammalian ionotropic glutamate receptors, was unable to provide evidence of a role for their plant homologs in sensing exogenous glutamate. We discuss the mechanism of l-glutamate sensing and the possible ecological significance of the observed l-glutamate-elicited changes in root architecture.

  2. Finding Biomarker Signatures in Pooled Sample Designs: A Simulation Framework for Methodological Comparisons

    Directory of Open Access Journals (Sweden)

    Anna Telaar

    2010-01-01

    Full Text Available Detection of discriminating patterns in gene expression data can be accomplished by using various methods of statistical learning. It has been proposed that sample pooling in this context would have negative effects; however, pooling cannot always be avoided. We propose a simulation framework to explicitly investigate the parameters of patterns, experimental design, noise, and choice of method in order to find out which effects on classification performance are to be expected. We use a two-group classification task and simulated gene expression data with independent differentially expressed genes as well as bivariate linear patterns and the combination of both. Our results show a clear increase of prediction error with pool size. For pooled training sets powered partial least squares discriminant analysis outperforms discriminance analysis, random forests, and support vector machines with linear or radial kernel for two of three simulated scenarios. The proposed simulation approach can be implemented to systematically investigate a number of additional scenarios of practical interest.

  3. Purification and characterization of gamma poly glutamic acid from newly Bacillus licheniformis NRC20.

    Science.gov (United States)

    Tork, Sanaa E; Aly, Magda M; Alakilli, Saleha Y; Al-Seeni, Madeha N

    2015-03-01

    γ-poly glutamic acid (γ-PGA) has received considerable attention for pharmaceutical and biomedical applications. γ-PGA from the newly isolate Bacillus licheniformis NRC20 was purified and characterized using diffusion distance agar plate, mass spectrometry and thin layer chromatography. All analysis indicated that γ-PGA is a homopolymer composed of glutamic acid. Its molecular weight was determined to be 1266 kDa. It was composed of L- and D-glutamic acid residues. An amplicon of 3050 represents the γ-PGA-coding genes was obtained, sequenced and submitted in genbank database. Its amino acid sequence showed high similarity with that obtained from B. licheniformis strains. The bacterium NRC 20 was independent of L-glutamic acid but the polymer production enhanced when cultivated in medium containing L-glutamic acid as the sole nitrogen source. Finally we can conclude that γ-PGA production from B. licheniformis NRC20 has many promised applications in medicine, industry and nanotechnology. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. [A Multi-arm Placebo-controlled Study with Glutamic Acid Conducted in Rostock in 1953/1954].

    Science.gov (United States)

    Häßler, Frank; Weirich, Steffen

    2017-09-01

    A Multi-arm Placebo-controlled Study with Glutamic Acid Conducted in Rostock in 1953/1954 Glutamic acid was commonly used in the treatment of intellectually disabled children in the 50s. Koch reported first results of an observation of 140 children treated with glutamic acid in 1952. In this line is the multi-arm placebo-controlled study reported here. The original study protocols were available. 58 children with speech problems who attending a school of special needs received glutamic acid, or vitamin B, or St.-John's-wort. The effect of glutamic acid was in few cases an improvement of attention. On the other hand restlessness and stutter increased. The majority of all reported a weight loss. The treatment with vitamin B showed a positive effect concerning concentration. The treatment with St.-John's wort was stopped caused by headache and vomiting in eight of nine cases. The results of the study reported here are unpublished. The reason may be that until the 60s the effects of glutamic acid in the treatment of intellectually disabled children were in generally overestimated.

  5. Visualization of nucleate pool boiling of freon 113

    International Nuclear Information System (INIS)

    Afify, M.A.; Fruman, D.H.

    1987-01-01

    The purpose of this investigation is to give a fine description of the behaviour of vapour bubbles in nucleate pool boiling at sites of known sizes using high speed photography. The shapes and growth history of isolated bubbles were determined for a variety of experimental conditions. Coalescence effects between two adjacent or consecutive bubbles were also visualized and the occurrence of vapour patches and continuous vapour columns was demonstrated. Quantitative analysis of the films allows to determine the history and nucleation characteristics of bubbles as a function of various parameters such as heat flux, liquid subcooling and size and nature of nucleation sites. These results are in good agreement with those found in the literature

  6. Effects of phosphoenolpyruvate carboxylase desensitization on glutamic acid production in Corynebacterium glutamicum ATCC 13032.

    Science.gov (United States)

    Wada, Masaru; Sawada, Kazunori; Ogura, Kotaro; Shimono, Yuta; Hagiwara, Takuya; Sugimoto, Masakazu; Onuki, Akiko; Yokota, Atsushi

    2016-02-01

    Phosphoenolpyruvate carboxylase (PEPC) in Corynebacterium glutamicum ATCC13032, a glutamic-acid producing actinobacterium, is subject to feedback inhibition by metabolic intermediates such as aspartic acid and 2-oxoglutaric acid, which implies the importance of PEPC in replenishing oxaloacetic acid into the TCA cycle. Here, we investigated the effects of feedback-insensitive PEPC on glutamic acid production. A single amino-acid substitution in PEPC, D299N, was found to relieve the feedback control by aspartic acid, but not by 2-oxoglutaric acid. A simple mutant, strain R1, having the D299N substitution in PEPC was constructed from ATCC 13032 using the double-crossover chromosome replacement technique. Strain R1 produced glutamic acid at a concentration of 31.0 g/L from 100 g/L glucose in a jar fermentor culture under biotin-limited conditions, which was significantly higher than that of the parent, 26.0 g/L (1.19-fold), indicative of the positive effect of desensitized PEPC on glutamic acid production. Another mutant, strain DR1, having both desensitized PEPC and PYK-gene deleted mutations, was constructed in a similar manner using strain D1 with a PYK-gene deleted mutation as the parent. This mutation had been shown to enhance glutamic acid production in our previous study. Although marginal, strain D1 produced higher glutamic acid, 28.8 g/L, than ATCC13032 (1.11-fold). In contrast, glutamic acid production by strain DR-1 was elevated up to 36.9 g/L, which was 1.42-fold higher than ATCC13032 and significantly higher than the other three strains. The results showed a synergistic effect of these two mutations on glutamic acid production in C. glutamicum. Copyright © 2015 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  7. Baseline dietary glutamic acid intake and the risk of colorectal cancer: The Rotterdam study.

    Science.gov (United States)

    Viana Veloso, Gilson G; Franco, Oscar H; Ruiter, Rikje; de Keyser, Catherina E; Hofman, Albert; Stricker, Bruno C; Kiefte-de Jong, Jessica C

    2016-03-15

    Animal studies have shown that glutamine supplementation may decrease colon carcinogenesis, but any relation with glutamine or its precursors has not been studied in humans. The primary aim of this study was to assess whether dietary glutamic acid intake was associated with colorectal cancer (CRC) risk in community-dwelling adults. A secondary aim was to evaluate whether the association could be modified by the body mass index (BMI). This study was embedded in the Rotterdam study, which included a prospective cohort from 1990 onward that consisted of 5362 subjects who were 55 years old or older and were free of CRC at the baseline. Glutamic acid was calculated as a percentage of the total protein intake with a validated food frequency questionnaire at the baseline. Incident cases of CRC were pathology-based. During follow-up, 242 subjects developed CRC. Baseline dietary glutamic acid intake was significantly associated with a lower risk of developing CRC (hazard ratio [HR] per percent increase in glutamic acid of protein, 0.78; 95% confidence interval [CI], 0.62-0.99). After stratification for BMI, the risk reduction for CRC by dietary glutamic acid was 42% for participants with a BMI ≤ 25 kg/m(2) (HR per percent increase in glutamic acid of protein, 0.58; 95% CI, 0.40-0.85), whereas no association was found in participants with a BMI > 25 kg/m(2) (HR per percent increase in glutamic acid of protein, 0.97; 95% CI, 0.73-1.31). Our data suggest that baseline dietary glutamic acid intake is associated with a lower risk of developing CRC, but this association may be mainly present in nonoverweight subjects. © 2015 American Cancer Society.

  8. Increase of extracellular glutamate concentration increases its oxidation and diminishes glucose oxidation in isolated mouse hippocampus: reversible by TFB-TBOA.

    Science.gov (United States)

    Torres, Felipe Vasconcelos; Hansen, Fernanda; Locks-Coelho, Lucas Doridio

    2013-08-01

    Glutamate concentration at the synaptic level must be kept low in order to prevent excitotoxicity. Astrocytes play a key role in brain energetics, and also astrocytic glutamate transporters are responsible for the vast majority of glutamate uptake in CNS. Experiments with primary astrocytic cultures suggest that increased influx of glutamate cotransported with sodium at astrocytes favors its flux to the tricarboxylic acid cycle instead of the glutamate-glutamine cycle. Although metabolic coupling can be considered an emergent field of research with important recent discoveries, some basic aspects of glutamate metabolism still have not been characterized in brain tissue. Therefore, the aim of this study was to investigate whether the presence of extracellular glutamate is able to modulate the use of glutamate and glucose as energetic substrates. For this purpose, isolated hippocampi of mice were incubated with radiolabeled substrates, and CO2 radioactivity and extracellular lactate were measured. Our results point to a diminished oxidation of glucose with increasing extracellular glutamate concentration, glutamate presumably being the fuel, and might suggest that oxidation of glutamate could buffer excitotoxic conditions by high glutamate concentrations. In addition, these findings were reversed when glutamate uptake by astrocytes was impaired by the presence of (3S)-3-[[3-[[4-(trifluoromethyl)benzoyl]amino]phenyl]methoxy]-L-aspartic acid (TFB-TBOA). Taken together, our findings argue against the lactate shuttle theory, because glutamate did not cause any detectable increase in extracellular lactate content (or, presumably, in glycolysis), because the glutamate is being used as fuel instead of going to glutamine and back to neurons. Copyright © 2013 Wiley Periodicals, Inc.

  9. Big city consultants shut down our pool : a shocking community pool gets checked for stray voltage

    Energy Technology Data Exchange (ETDEWEB)

    Lynch, P. [Power Line Systems Engineering Inc., Markham, ON (Canada)

    2009-12-15

    This article discussed an investigation conducted at a community pool where swimmers complained of receiving electrical shocks both in the pool and on the pool's deck area. Electrical measurements taken at the pool revealed current flows from the pool water to various points around the deck area. Measured current flow in the pool area was 30 amps even when the main pool service breaker was opened to shut off power to the entire facility. Thirty amps of primary neutral current was then measured on the primary side aerial neutral in front of the pool. A 10 amp primary feeder from the pool joined up with the complex's primary neutral wire to increase the neutral current to 40 amps. The combined 40 amps current then returned to the secondary side of a nearby utility transformer substation. The study showed that the underground wet low-resistance grounded surface area of the pool was attracting the 30 amps of utility current from the surrounding ground area. The local utility disconnected the primary and secondary neutral interconnection at the pool's main 600-volt step-down transformer. The pool deck was removed in order to install additional copper bonding grounds. In order to avert serious injuries, many experts propose that all electric utilities should be required by law to reconfigure their power systems to prevent primary power neutral currents from entering private buildings. 1 tab., 2 figs.

  10. Polyglutamate copolymers as a tissue-engineering platform: polymer scaffold modification through aminolysis of poly(.gamma.-benzyl-L-glutamate-co-2,2,2-.gamma.-trichlorethyl-L-glutamate)

    Czech Academy of Sciences Publication Activity Database

    Svobodová, Jana; Rypáček, František

    2012-01-01

    Roč. 48, č. 1 (2012), s. 183-190 ISSN 0014-3057 R&D Projects: GA AV ČR KJB400500904; GA ČR GAP108/11/1857; GA MŠk 1M0538 Institutional research plan: CEZ:AV0Z40500505 Keywords : poly(.gamma.-benzyl-L-glutamate) * 2,2,2-.gamma.-trichlorethyl-L-glutamate * fibres Subject RIV: CD - Macromolecular Chemistry Impact factor: 2.562, year: 2012

  11. poolHiTS: A Shifted Transversal Design based pooling strategy for high-throughput drug screening

    Directory of Open Access Journals (Sweden)

    Woolf Peter J

    2008-05-01

    Full Text Available Abstract Background A key goal of drug discovery is to increase the throughput of small molecule screens without sacrificing screening accuracy. High-throughput screening (HTS in drug discovery involves testing a large number of compounds in a biological assay to identify active compounds. Normally, molecules from a large compound library are tested individually to identify the activity of each molecule. Usually a small number of compounds are found to be active, however the presence of false positive and negative testing errors suggests that this one-drug one-assay screening strategy can be significantly improved. Pooling designs are testing schemes that test mixtures of compounds in each assay, thereby generating a screen of the whole compound library in fewer tests. By repeatedly testing compounds in different combinations, pooling designs also allow for error-correction. These pooled designs, for specific experiment parameters, can be simply and efficiently created using the Shifted Transversal Design (STD pooling algorithm. However, drug screening contains a number of key constraints that require specific modifications if this pooling approach is to be useful for practical screen designs. Results In this paper, we introduce a pooling strategy called poolHiTS (Pooled High-Throughput Screening which is based on the STD algorithm. In poolHiTS, we implement a limit on the number of compounds that can be mixed in a single assay. In addition, we show that the STD-based pooling strategy is limited in the error-correction that it can achieve. Due to the mixing constraint, we show that it is more efficient to split a large library into smaller blocks of compounds, which are then tested using an optimized strategy repeated for each block. We package the optimal block selection algorithm into poolHiTS. The MATLAB codes for the poolHiTS algorithm and the corresponding decoding strategy are also provided. Conclusion We have produced a practical version

  12. A model based on Rock-Eval thermal analysis to quantify the size of the centennially persistent organic carbon pool in temperate soils

    Science.gov (United States)

    Cécillon, Lauric; Baudin, François; Chenu, Claire; Houot, Sabine; Jolivet, Romain; Kätterer, Thomas; Lutfalla, Suzanne; Macdonald, Andy; van Oort, Folkert; Plante, Alain F.; Savignac, Florence; Soucémarianadin, Laure N.; Barré, Pierre

    2018-05-01

    Changes in global soil carbon stocks have considerable potential to influence the course of future climate change. However, a portion of soil organic carbon (SOC) has a very long residence time ( > 100 years) and may not contribute significantly to terrestrial greenhouse gas emissions during the next century. The size of this persistent SOC reservoir is presumed to be large. Consequently, it is a key parameter required for the initialization of SOC dynamics in ecosystem and Earth system models, but there is considerable uncertainty in the methods used to quantify it. Thermal analysis methods provide cost-effective information on SOC thermal stability that has been shown to be qualitatively related to SOC biogeochemical stability. The objective of this work was to build the first quantitative model of the size of the centennially persistent SOC pool based on thermal analysis. We used a unique set of 118 archived soil samples from four agronomic experiments in northwestern Europe with long-term bare fallow and non-bare fallow treatments (e.g., manure amendment, cropland and grassland) as a sample set for which estimating the size of the centennially persistent SOC pool is relatively straightforward. At each experimental site, we estimated the average concentration of centennially persistent SOC and its uncertainty by applying a Bayesian curve-fitting method to the observed declining SOC concentration over the duration of the long-term bare fallow treatment. Overall, the estimated concentrations of centennially persistent SOC ranged from 5 to 11 g C kg-1 of soil (lowest and highest boundaries of four 95 % confidence intervals). Then, by dividing the site-specific concentrations of persistent SOC by the total SOC concentration, we could estimate the proportion of centennially persistent SOC in the 118 archived soil samples and the associated uncertainty. The proportion of centennially persistent SOC ranged from 0.14 (standard deviation of 0.01) to 1 (standard deviation

  13. A model based on Rock-Eval thermal analysis to quantify the size of the centennially persistent organic carbon pool in temperate soils

    Directory of Open Access Journals (Sweden)

    L. Cécillon

    2018-05-01

    Full Text Available Changes in global soil carbon stocks have considerable potential to influence the course of future climate change. However, a portion of soil organic carbon (SOC has a very long residence time ( >  100 years and may not contribute significantly to terrestrial greenhouse gas emissions during the next century. The size of this persistent SOC reservoir is presumed to be large. Consequently, it is a key parameter required for the initialization of SOC dynamics in ecosystem and Earth system models, but there is considerable uncertainty in the methods used to quantify it. Thermal analysis methods provide cost-effective information on SOC thermal stability that has been shown to be qualitatively related to SOC biogeochemical stability. The objective of this work was to build the first quantitative model of the size of the centennially persistent SOC pool based on thermal analysis. We used a unique set of 118 archived soil samples from four agronomic experiments in northwestern Europe with long-term bare fallow and non-bare fallow treatments (e.g., manure amendment, cropland and grassland as a sample set for which estimating the size of the centennially persistent SOC pool is relatively straightforward. At each experimental site, we estimated the average concentration of centennially persistent SOC and its uncertainty by applying a Bayesian curve-fitting method to the observed declining SOC concentration over the duration of the long-term bare fallow treatment. Overall, the estimated concentrations of centennially persistent SOC ranged from 5 to 11 g C kg−1 of soil (lowest and highest boundaries of four 95 % confidence intervals. Then, by dividing the site-specific concentrations of persistent SOC by the total SOC concentration, we could estimate the proportion of centennially persistent SOC in the 118 archived soil samples and the associated uncertainty. The proportion of centennially persistent SOC ranged from 0.14 (standard deviation

  14. The effect of nucleotides and adenosine on stimulus-evoked glutamate release from rat brain cortical slices.

    Science.gov (United States)

    Bennett, G C; Boarder, M R

    2000-10-01

    Evidence has previously been presented that P1 receptors for adenosine, and P2 receptors for nucleotides such as ATP, regulate stimulus-evoked release of biogenic amines from nerve terminals in the brain. Here we investigated whether adenosine and nucleotides exert presynaptic control over depolarisation-elicited glutamate release. Slices of rat brain cortex were perfused and stimulated with pulses of 46 mM K(+) in the presence of the glutamate uptake inhibitor L-trans-pyrrolidine-2,4-dicarboxylic acid (0.2 mM). High K(+) substantially increased efflux of glutamate from the slices. Basal glutamate release was unchanged by the presence of nucleotides or adenosine at concentrations of 300 microM. Adenosine, ATP, ADP and adenosine 5'-O-(3-thiotriphoshate) at 300 microM attenuated depolarisation-evoked release of glutamate. However UTP, 2-methylthio ATP, 2-methylthio ADP, and alpha,beta-methylene ATP at 300 microM had no effect on stimulated glutamate efflux. Adenosine deaminase blocked the effect of adenosine, but left the response to ATP unchanged. The A(1) antagonist 8-cyclopentyl-1, 3-dipropylxanthine antagonised the inhibitory effect of both adenosine and ATP. Cibacron blue 3GA inhibited stimulus-evoked glutamate release when applied alone. When cibacron blue 3GA was present with ATP, stimulus-evoked glutamate release was almost eliminated. However, this P2 antagonist had no effect on the inhibition by adenosine. These results show that the release of glutamate from depolarised nerve terminals of the rat cerebral cortex is inhibited by adenosine and ATP. ATP appears to act directly and not through conversion to adenosine.

  15. Group I Metabotropic Glutamate Receptors

    DEFF Research Database (Denmark)

    Erichsen, Julie Ladeby; Blaabjerg, Morten; Bogetofte Thomasen, Helle

    2015-01-01

    differentiated an immortalized, forebrain-derived stem cell line in the presence or absence of glutamate and with addition of either the group I mGluR agonist DHPG or the selective antagonists; MPEP (mGluR5) and LY367385 (mGluR1). Characterization of differentiated cells revealed that both mGluR1 and mGluR5 were...

  16. A comprehensive review on pool boiling of nanofluids

    International Nuclear Information System (INIS)

    Ciloglu, Dogan; Bolukbasi, Abdurrahim

    2015-01-01

    Nanofluids are nanoparticle suspensions of small particle size and low concentration dispersed in base fluids such as water, oil and ethylene glycol. These fluids have been considered by researchers as a unique heat transfer carrier because of their thermophysical properties and a great number of potential benefits in traditional thermal engineering applications, including power generation, transportation, air conditioning, electronics devices and cooling systems. Many attempts have been made in the literature on nanofluid boiling; however, data on the boiling heat transfer coefficient (HTC) and the critical heat flux (CHF) have been inconsistent. This paper presents a review of recent researches on the pool boiling heat transfer behaviour of nanofluid. First, the development of nanofluids and their potential applications are briefly given. Then, the effects of various parameters on nanofluids pool boiling are discussed in detail. - Highlights: • A review on the pool boiling heat transfer of nanofluid is presented and discussed. • Nanoparticle deposition considerably affects the boiling heat transfer. • The HTC decreases due to the low contact angle and the high adhesion energy. • The HTC increases due to the formation of the new cavities and liquid suction. • The CHF increases due to the increase in roughness, wettability and capillarity

  17. Enhanced production of poly glutamic acid by Bacillus sp. SW1-2 ...

    African Journals Online (AJOL)

    Bacillus sp. SW1-2 producing poly glutamic acid (PGA), locally isolated from Eastern province in Saudi Arabia, was characterized and identified based on 16S rRNA gene sequencing. Phylogenetic analysis revealed its closeness to Bacillus megaterium. The homopolymer consists mainly of glutamic as indicated in the ...

  18. Secretory phospholipase A2-mediated neuronal cell death involves glutamate ionotropic receptors

    DEFF Research Database (Denmark)

    Kolko, Miriam; de Turco, Elena B; Diemer, Nils Henrik

    2002-01-01

    To define the significance of glutamate ionotropic receptors in sPLA -mediated neuronal cell death we used the NMDA receptor antagonist MK-801 and the AMPA receptor antagonist PNQX. In primary neuronal cell cultures both MK-801 and PNQX inhibited sPLA - and glutamate-induced neuronal death. [ H...

  19. Elevated baseline serum glutamate as a pharmacometabolomic biomarker for acamprosate treatment outcome in alcohol-dependent subjects

    Science.gov (United States)

    Nam, H W; Karpyak, V M; Hinton, D J; Geske, J R; Ho, A M C; Prieto, M L; Biernacka, J M; Frye, M A; Weinshilboum, R M; Choi, D-S

    2015-01-01

    Acamprosate has been widely used since the Food and Drug Administration approved the medication for treatment of alcohol use disorders (AUDs) in 2004. Although the detailed molecular mechanism of acamprosate remains unclear, it has been largely known that acamprosate inhibits glutamate action in the brain. However, AUD is a complex and heterogeneous disorder. Thus, biomarkers are required to prescribe this medication to patients who will have the highest likelihood of responding positively. To identify pharmacometabolomic biomarkers of acamprosate response, we utilized serum samples from 120 alcohol-dependent subjects, including 71 responders (maintained continuous abstinence) and 49 non-responders (any alcohol use) during 12 weeks of acamprosate treatment. Notably, baseline serum glutamate levels were significantly higher in responders compared with non-responders. Importantly, serum glutamate levels of responders are normalized after acamprosate treatment, whereas there was no significant glutamate change in non-responders. Subsequent functional studies in animal models revealed that, in the absence of alcohol, acamprosate activates glutamine synthetase, which synthesizes glutamine from glutamate and ammonia. These results suggest that acamprosate reduces serum glutamate levels for those who have elevated baseline serum glutamate levels among responders. Taken together, our findings demonstrate that elevated baseline serum glutamate levels are a potential biomarker associated with positive acamprosate response, which is an important step towards development of a personalized approach to treatment for AUD. PMID:26285131

  20. Overrepresentation of glutamate signaling in Alzheimer's disease: network-based pathway enrichment using meta-analysis of genome-wide association studies.

    Directory of Open Access Journals (Sweden)

    Eduardo Pérez-Palma

    Full Text Available Genome-wide association studies (GWAS have successfully identified several risk loci for Alzheimer's disease (AD. Nonetheless, these loci do not explain the entire susceptibility of the disease, suggesting that other genetic contributions remain to be identified. Here, we performed a meta-analysis combining data of 4,569 individuals (2,540 cases and 2,029 healthy controls derived from three publicly available GWAS in AD and replicated a broad genomic region (>248,000 bp associated with the disease near the APOE/TOMM40 locus in chromosome 19. To detect minor effect size contributions that could help to explain the remaining genetic risk, we conducted network-based pathway analyses either by extracting gene-wise p-values (GW, defined as the single strongest association signal within a gene, or calculated a more stringent gene-based association p-value using the extended Simes (GATES procedure. Comparison of these strategies revealed that ontological sub-networks (SNs involved in glutamate signaling were significantly overrepresented in AD (p<2.7×10(-11, p<1.9×10(-11; GW and GATES, respectively. Notably, glutamate signaling SNs were also found to be significantly overrepresented (p<5.1×10(-8 in the Alzheimer's disease Neuroimaging Initiative (ADNI study, which was used as a targeted replication sample. Interestingly, components of the glutamate signaling SNs are coordinately expressed in disease-related tissues, which are tightly related to known pathological hallmarks of AD. Our findings suggest that genetic variation within glutamate signaling contributes to the remaining genetic risk of AD and support the notion that functional biological networks should be targeted in future therapies aimed to prevent or treat this devastating neurological disorder.

  1. Identification of the glutaminase genes of Aspergillus sojae involved in glutamate production during soy sauce fermentation.

    Science.gov (United States)

    Ito, Kotaro; Koyama, Yasuji; Hanya, Yoshiki

    2013-01-01

    Glutaminase, an enzyme that catalyzes the conversion of L-glutamine to L-glutamate, enhances the umami taste in soy sauce. The Aspergillus sojae genome contains 10 glutaminase genes. In this study, we estimated that approximately 60% of the glutamate in soy sauce is produced through the glutaminase reaction. To determine which glutaminase is involved in soy sauce glutamate production, we prepared soy sauces using single and multiple glutaminase gene disruptants of A. sojae. The glutamate concentration in soy sauce prepared using the ΔgahA-ΔgahB-ΔggtA-Δgls disruptant was approximately 60% lower than that in the control strain, whereas it was decreased by approximately 20-30% in the ΔgahA-ΔgahB disruptant. However, the glutamate concentration was unchanged in the soy sauces prepared using the ΔgahA-ΔggtA-Δgls and ΔgahB-ΔggtA-Δgls disruptants. These results indicate that four glutaminases are involved in glutamate production in soy sauce, and that the peptidoglutaminase activities of GahA and GahB increase the glutamate concentration in soy sauce.

  2. Regulation of dopamine D1 receptor dynamics within the postsynaptic density of hippocampal glutamate synapses.

    Directory of Open Access Journals (Sweden)

    Laurent Ladepeche

    Full Text Available Dopamine receptor potently modulates glutamate signalling, synaptic plasticity and neuronal network adaptations in various pathophysiological processes. Although key intracellular signalling cascades have been identified, the cellular mechanism by which dopamine and glutamate receptor-mediated signalling interplay at glutamate synapse remain poorly understood. Among the cellular mechanisms proposed to aggregate D1R in glutamate synapses, the direct interaction between D1R and the scaffold protein PSD95 or the direct interaction with the glutamate NMDA receptor (NMDAR have been proposed. To tackle this question we here used high-resolution single nanoparticle imaging since it provides a powerful way to investigate at the sub-micron resolution the dynamic interaction between these partners in live synapses. We demonstrate in hippocampal neuronal networks that dopamine D1 receptors (D1R laterally diffuse within glutamate synapses, in which their diffusion is reduced. Disrupting the interaction between D1R and PSD95, through genetical manipulation and competing peptide, did not affect D1R dynamics in glutamatergic synapses. However, preventing the physical interaction between D1R and the GluN1 subunit of NMDAR abolished the synaptic stabilization of diffusing D1R. Together, these data provide direct evidence that the interaction between D1R and NMDAR in synapses participate in the building of the dopamine-receptor-mediated signalling, and most likely to the glutamate-dopamine cross-talk.

  3. Oleuropein isolated from Fraxinus rhynchophylla inhibits glutamate-induced neuronal cell death by attenuating mitochondrial dysfunction.

    Science.gov (United States)

    Kim, Mi Hye; Min, Ju-Sik; Lee, Joon Yeop; Chae, Unbin; Yang, Eun-Ju; Song, Kyung-Sik; Lee, Hyun-Shik; Lee, Hong Jun; Lee, Sang-Rae; Lee, Dong-Seok

    2017-04-27

    Glutamate-induced neurotoxicity is related to excessive oxidative stress accumulation and results in the increase of neuronal cell death. In addition, glutamate has been reported to lead to neurodegenerative diseases, including Parkinson's and Alzheimer's diseases.It is well known that Fraxinus rhynchophylla contains a significant level of oleuropein (Ole), which exerts various pharmacological effects. However, the mechanism of neuroprotective effects of Ole is still poorly defined. In this study, we aimed to investigate whether Ole prevents glutamate-induced toxicity in HT-22 hippocampal neuronal cells. The exposure of the glutamate treatment caused neuronal cell death through an alteration of Bax/Bcl-2 expression and translocation of mitochondrial apoptosis-inducing factor (AIF) to the cytoplasm of HT-22 cells. In addition, glutamate induced an increase in dephosphorylation of dynamin-related protein 1 (Drp1), mitochondrial fragmentation, and mitochondrial dysfunction. The pretreatment of Ole decreased Bax expression, increased Bcl-2 expression, and inhibited the translocation of mitochondrial AIF to the cytoplasm. Furthermore, Ole amended a glutamate-induced mitochondrial dynamic imbalance and reduced the number of cells with fragmented mitochondria, regulating the phosphorylation of Drp1 at amino acid residue serine 637. In conclusion, our results show that Ole has a preventive effect against glutamate-induced toxicity in HT-22 hippocampal neuronal cells. Therefore, these data imply that Ole may be an efficient approach for the treatment of neurodegenerative diseases.

  4. Effect of 8-bromo-cAMP and dexamethasone on glutamate metabolism in rat astrocytes

    International Nuclear Information System (INIS)

    Zielke, H.R.; Tildon, J.T.; Landry, M.E.; Max, S.R.

    1990-01-01

    Glutamine synthetase (GS) activity in cultured rat astrocytes was measured in extracts and compared to the intracellular rate of glutamine synthesis by intact control astrocytes or astrocytes exposed to 1 mM 8-bromo-cAMP (8Br-cAMP) + 1 microM dexamethasone (DEX) for 4 days. GS activity in extracts of astrocytes treated with 8Br-cAMP + DEX was 7.5 times greater than the activity in extracts of control astrocytes. In contrast, the intracellular rate of glutamine synthesis by intact cells increased only 2-fold, suggesting that additional intracellular effectors regulate the expression of GS activity inside the intact cell. The rate of glutamine synthesis by astrocytes was 4.3 times greater in MEM than in HEPES buffered Hank's salts. Synthesis of glutamine by intact astrocytes cultured in MEM was independent of the external glutamine or ammonia concentrations but was increased by higher extracellular glutamate concentrations. In studies with intact astrocytes 80% of the original [U- 14 C]glutamate was recovered in the medium as radioactive glutamine, 2-3% as aspartate, and 7% as glutamate after 2 hours for both control and treated astrocytes. The results suggest: (1) astrocytes are highly efficient in the conversion of glutamate to glutamine; (2) induction of GS activity increases the rate of glutamate conversion to glutamine by astrocytes and the rate of glutamine release into the medium; (3) endogenous intracellular regulators of GS activity control the flux of glutamate through this enzymatic reaction; and (4) the composition of the medium alters the rate of glutamine synthesis from external glutamate

  5. Sex Differences in Psychiatric Disease: A Focus on the Glutamate System

    Directory of Open Access Journals (Sweden)

    Megan M. Wickens

    2018-06-01

    Full Text Available Alterations in glutamate, the primary excitatory neurotransmitter in the brain, are implicated in several psychiatric diseases. Many of these psychiatric diseases display epidemiological sex differences, with either males or females exhibiting different symptoms or disease prevalence. However, little work has considered the interaction of disrupted glutamatergic transmission and sex on disease states. This review describes the clinical and preclinical evidence for these sex differences with a focus on two conditions that are more prevalent in women: Alzheimer's disease and major depressive disorder, and three conditions that are more prevalent in men: schizophrenia, autism spectrum disorder, and attention deficit hyperactivity disorder. These studies reveal sex differences at multiple levels in the glutamate system including metabolic markers, receptor levels, genetic interactions, and therapeutic responses to glutamatergic drugs. Our survey of the current literature revealed a considerable need for more evaluations of sex differences in future studies examining the role of the glutamate system in psychiatric disease. Gaining a more thorough understanding of how sex differences in the glutamate system contribute to psychiatric disease could provide novel avenues for the development of sex-specific pharmacotherapies.

  6. The effect of chronic ethanol on glutamate binding in human and rat brain

    International Nuclear Information System (INIS)

    Cummins, J.T.; Sack, M.; von Hungen, K.

    1990-01-01

    Quantitative autoradiographic techniques demonstrate that chronic alcohol administration causes a decrease in [ 3 H]-glutamate binding to hippocampal N-methyl-D-aspartate (NMDA) receptors. A 14% decrease in [ 3 H]-glutamate binding in the hippocampal CA 1 region is seen both in the rat after five days of ethanol administration and in postmortem hippocampal tissues from alcoholics. In the rat, 24 hr ethanol withdrawal values are intermediate between control and alcohol binding levels. There was no significant effect of ethanol on [ 3 H]-glutamate binding in the cortex or caudate

  7. Improvement of sampling plans for Salmonella detection in pooled table eggs by use of real-time PCR

    DEFF Research Database (Denmark)

    Pasquali, Frédérique; De Cesare, Alessandra; Valero, Antonio

    2014-01-01

    Eggs and egg products have been described as the most critical food vehicles of salmonellosis. The prevalence and level of contamination of Salmonella on table eggs are low, which severely affects the sensitivity of sampling plans applied voluntarily in some European countries, where one to five...... pools of 10 eggs are tested by the culture based reference method ISO 6579:2004. In the current study we have compared the testing-sensitivity of the reference culture method ISO 6579:2004 and an alternative real-time PCR method on Salmonella contaminated egg-pool of different sizes (4-9 uninfected eggs...... mixed with one contaminated egg) and contamination levels (10°-10(1), 10(1)-10(2), 10(2)-10(3)CFU/eggshell). Two hundred and seventy samples corresponding to 15 replicates per pool size and inoculum level were tested. At the lowest contamination level real-time PCR detected Salmonella in 40...

  8. The impact of blood pressure on hippocampal glutamate and mnestic function.

    Science.gov (United States)

    Westhoff, T H; Schubert, F; Wirth, C; Joppke, M; Klär, A A; Zidek, W; Gallinat, J

    2011-04-01

    Hypertension is associated with an increased risk of cognitive decline, which is generally regarded as a consequence of advanced cerebral atherosclerosis. Many hypertensive patients, however, suffer from cognitive decline long before they have any signs of cerebrovascular disease. Therefore, this study examines direct effects of blood pressure on neurotransmitter status in the hippocampus, a vulnerable cerebral structure relevant for memory consolidation. Absolute glutamate concentration and N-acetylaspartate (NAA) concentration as an alternative marker of neuronal integrity were determined in the hippocampus and the cerebral cortex (anterior cingulate cortex; ACC) by 3-T proton magnetic resonance spectroscopy in 16 probands without any history of cerebrovascular disease. Memory function was tested by the auditory verbal learning test (AVLT) and the rivermead behavioural memory test (RBMT). Arterial stiffness was assessed by augmentation index (AI). Mean arterial pressure showed a significant negative age-adjusted correlation to absolute glutamate concentrations in the hippocampus (R=-0.655, P=0.011), but not in the ACC. There was no significant correlation of mean arterial pressure and NAA in either hippocampus or ACC. AI did not affect hippocampal glutamate. Moreover, there was a significant negative correlation between mean arterial pressure and AVLT (r=-0.558, P=0.025) and RBMT score (r=-0.555, P=0.026). There is an inverse relation between blood pressure and the concentration of hippocampal glutamate. Glutamate is essential for long-term potentiation, the neurobiological correlate for memory formation in the hippocampus. Thus, hypertension-associated cognitive decline may not only be mediated by structural atherosclerotic wall changes, but also by functional changes in neurotransmission.

  9. GLT-1 Transport Stoichiometry Is Constant at Low and High Glutamate Concentrations when Chloride Is Substituted by Gluconate.

    Directory of Open Access Journals (Sweden)

    Anatoli Y Kabakov

    Full Text Available Glutamate is the major excitatory neurotransmitter, but prolonged exposure even at micromolar concentrations causes neuronal death. Extracellular glutamate is maintained at nanomolar level by glutamate transporters, which, however, may reverse transport and release glutamate. If and when the reverse occurs depends on glutamate transport stoichiometry (GTS. Previously we found that in the presence of chloride, the coupled GLT-1 glutamate transporter current and its relationship to radiolabeled glutamate flux significantly decreased when extracellular glutamate concentration increased above 0.2 mM, which implies a change in GTS. Such high concentrations are feasible near GLT-1 expressed close to synaptic release site during excitatory neurotransmission. The aim of this study was to determine GLT-1 GTS at both low (19-75 μM and high (300-1200 μM glutamate concentration ranges. GTS experiments were conducted in the absence of chloride to avoid contributions by the GLT-1 uncoupled chloride conductance. Mathematical analysis of the transporter thermodynamic equilibrium allowed us to derive equations revealing the number of a particular type of ion transported per elementary charge based on the measurements of the transporter reversal potential. We found that GLT-1a expressed in COS-7 cells co-transports 1.5 Na+, 0.5 Glu-, 0.5 H+ and counter-transports 0.6 K+ per elementary charge in both glutamate concentration ranges, and at both 37°C and 26°C temperatures. The thermodynamic parameter Q10 = 2.4 for GLT-1 turnover rate of 19 s-1 (37°C, -50 mV remained constant in the 10 μM-10 mM glutamate concentration range. Importantly, the previously reported decrease in the current/flux ratio at high glutamate concentration was not seen in the absence of chloride in both COS-7 cells and cultured rat neurons. Therefore, only in the absence of chloride, GLT-1 GTS remains constant at all glutamate concentrations. Possible explanations for why apparent GTS might

  10. Markers of glutamate signaling in cerebrospinal fluid and serum from patients with bipolar disorder and healthy controls.

    Science.gov (United States)

    Pålsson, Erik; Jakobsson, Joel; Södersten, Kristoffer; Fujita, Yuko; Sellgren, Carl; Ekman, Carl-Johan; Ågren, Hans; Hashimoto, Kenji; Landén, Mikael

    2015-01-01

    Glutamate is the major excitatory neurotransmitter in the brain. Aberrations in glutamate signaling have been linked to the pathophysiology of mood disorders. Increased plasma levels of glutamate as well as higher glutamine+glutamate levels in the brain have been demonstrated in patients with bipolar disorder as compared to healthy controls. In this study, we explored the glutamate hypothesis of bipolar disorder by examining peripheral and central levels of amino acids related to glutamate signaling. A total of 215 patients with bipolar disorder and 112 healthy controls from the Swedish St. Göran bipolar project were included in this study. Glutamate, glutamine, glycine, L-serine and D-serine levels were determined in serum and in cerebrospinal fluid using high performance liquid chromatography with fluorescence detection. Serum levels of glutamine, glycine and D-serine were significantly higher whereas L-serine levels were lower in patients with bipolar disorder as compared to controls. No differences between the patient and control group in amino acid levels were observed in cerebrospinal fluid. The observed differences in serum amino acid levels may be interpreted as a systemic aberration in amino acid metabolism that affects several amino acids related to glutamate signaling. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

  11. Gender-specific desensitization of group I metabotropic glutamate receptors after maternal l-glutamate intake during lactation.

    Science.gov (United States)

    López-Zapata, Antonio; León-Navarro, David Agustín; Crespo, María; Martín, Mairena

    2018-04-22

    In the present work we have studied the effect of maternal intake of l-Glutamate (l-Glu) (1 g/L) during lactation on group I mGluR transduction pathway in brain plasma membrane from 15 days-old neonates. Results obtained have shown that maternal l-glutamate intake did not significantly affect neither weights of pups nor negative geotaxis reflex, an index of neurobehavioral development, but increased l-Glu plasma level in both male and female neonates. In male neonates, maternal l-Glu intake evoked a loss of mGluR 1 whereas no variation on mGluR 5 was observed as revealed by Western-blotting assay. The loss of mGlu 1 R was accompanied by a decrease on l-Glu-stimulated phospholipase C activity suggesting, therefore, a loss of group I mGluR functionality. Concerning female neonates, no variations were detected neither mGluR 1 nor mGluR 5 and group I mGluR functionality was also preserved. Copyright © 2018 ISDN. Published by Elsevier Ltd. All rights reserved.

  12. Elevated glutamine/glutamate ratio in cerebrospinal fluid of first episode and drug naive schizophrenic patients

    Directory of Open Access Journals (Sweden)

    Lindström Leif H

    2005-01-01

    Full Text Available Abstract Background Recent magnetic resonance spectroscopy (MRS studies report that glutamine is altered in the brains of schizophrenic patients. There were also conflicting findings on glutamate in cerebrospinal fluid (CSF of schizophrenic patients, and absent for glutamine. This study aims to clarify the question of glutamine and glutamate in CSF of first episode and drug naive schizophrenic patients. Method Levels of glutamine and glutamate in CSF of 25 first episode and drug-naive male schizophrenic patients and 17 age-matched male healthy controls were measured by a high performance liquid chromatography. Results The ratio (126.1 (median, 117.7 ± 27.4 (mean ± S.D. of glutamine to glutamate in the CSF of patients was significantly (z = -3.29, p = 0.001 higher than that (81.01 (median, 89.1 ± 22.5 (mean ± S.D. of normal controls although each level of glutamine and glutamate in patients was not different from that of normal controls. Conclusion Our data suggests that a disfunction in glutamate-glutamine cycle in the brain may play a role in the pathophysiology of schizophrenia.

  13. Pool scrubbing

    International Nuclear Information System (INIS)

    Lopez-Jimenez, J.; Herranz, J.; Escudero, M.J.; Espigares, M.M.; Peyres, V.; Polo, J.; Kortz, Ch.; Koch, M.K.; Brockmeier, U.; Unger, H.; Dutton, L.M.C.; Smedley, Ch.; Trow, W.; Jones, A.V.; Bonanni, E.; Calvo, M.; Alonso, A.

    1996-12-01

    The Source Term Project in the Third Frame Work Programme of the European Union Was conducted under and important joined effort on pool scrubbing research. CIEMAT was the Task Manager of the project and several other organizations participated in it: JRC-Ispra, NNC Limited, RUB-NES and UPM. The project was divided into several tasks. A peer review of the models in the pool scrubbing codes SPARC90 and BUSCA-AUG92 was made, considering the different aspects in the hydrodynamic phenomenology, particle retention and fission product vapor abortions. Several dominant risk accident sequences were analyzed with MAAP, SPARC90 and BUSCA-AUG92 codes, and the predictions were compared. A churn-turbulent model was developed for the hydrodynamic behaviour of the pool. Finally, an experimental programme in the PECA facility of CIEMAT was conducted in order to study the decontamination factor under jet injection regime, and the experimental observations were compared with the SPARC and BUSCA codes. (Author)

  14. Solubilization, partial purification, and reconstitution of glutamate- and N-methyl-D-aspartate-activated cation channels from brain synaptic membranes

    International Nuclear Information System (INIS)

    Ly, A.M.; Michaelis, E.K.

    1991-01-01

    L-Glutamate-activated cation channel proteins from rat brain synaptic membranes were solubilized, partially purified, and reconstituted into liposomes. Optimal conditions for solubilization and reconstitution included treatment of the membranes with nonionic detergents in the presence of neutral phospholipids plus glycerol. Quench-flow procedures were developed to characterize the rapid kinetics of ion flux induced by receptor agonists. [ 14 C]Methylamine, a cation that permeates through the open channel of both vertebrate and invertebrate glutamate receptors, was used to measure the activity of glutamate receptor-ion channel complexes in reconstituted liposomes. L-Glutamate caused an increase in the rate of [ 14 C]methylamine influx into liposomes reconstituted with either solubilized membrane proteins or partially purified glutamate-binding proteins. Of the major glutamate receptor agonists, only N-methyl-D-aspartate activated cation fluxes in liposomes reconstituted with glutamate-binding proteins. In liposomes reconstituted with glutamate-binding proteins, N-methyl-D-aspartate- or glutamate-induced influx of NA + led to a transient increase in the influx of the lipid-permeable anion probe S 14 CN - . These results indicate the functional reconstitution of N-methyl-D-aspartate-sensitive glutamate receptors and the role of the ∼69-kDa protein in the function of these ion channels

  15. Analysis of an open-air swimming pool solar heating system by using an experimentally validated TRNSYS model

    Energy Technology Data Exchange (ETDEWEB)

    Ruiz, Elisa; Martinez, Pedro J. [Universidad Miguel Hernandez - Edificio Torreblanca, Avda. de la Universidad s/n, 03202 Elche (Spain)

    2010-01-15

    In the case of private outdoor swimming pools, seldom larger than 100 m{sup 2}, conventional auxiliary heating systems are being installed less and less. Solar heating is an option to extend the swimming season. The temperature evolution of an open-air swimming pool highly depends on the wind speed directly on the water surface, which at the same time is influenced by the surroundings of the pool. In this paper, the TRNSYS model of a private open-air pool with a 50-m{sup 2} surface was validated by registering the water temperature evolution and the meteorological data at the pool site. Evaporation is the main component of energy loss in swimming pools. Six different sets of constants found in literature were considered to evaluate the evaporative heat transfer coefficient with the purpose of finding the most suitable one for the TRNSYS pool model. In order to do that, the evolution of the pool water temperature predicted by the TRNSYS pool model was compared with the experimentally registered one. The simulation with TRNSYS of the total system, including the swimming pool and the absorber circuit integrated into the existing filter circuit, provided information regarding the increase of the pool temperature for different collector areas during the swimming season. This knowledge, together with the economic costs, support the decision about the absorber field size. (author)

  16. A novel reagentless glutamate microband biosensor for real-time cell toxicity monitoring

    Energy Technology Data Exchange (ETDEWEB)

    Hughes, G.; Pemberton, R.M. [Centre for Research in Biosciences, Faculty of Health and Applied Sciences, University of the West of England, Bristol, Coldharbour Lane, Bristol, BS16 1QY (United Kingdom); Fielden, P.R. [Department of Chemistry, Lancaster University, Bailrigg, Lancaster, LA1 4YB (United Kingdom); Hart, J.P., E-mail: john.hart@uwe.ac.uk [Centre for Research in Biosciences, Faculty of Health and Applied Sciences, University of the West of England, Bristol, Coldharbour Lane, Bristol, BS16 1QY (United Kingdom)

    2016-08-24

    A reagentless glutamate biosensor was applied to the determination of glutamate released from liver hepatocellular carcinoma cells (HepG2) in response to toxic challenge from various concentrations of paracetamol. A screen printed carbon electrode (SPCE) containing the electrocatalyst Meldola's Blue (MB-SPCE) served as the electron mediator for the oxidation of NADH. A mixture of the enzyme glutamate dehydrogenase (GLDH), cofactor nicotinamide adenine dinucleotide (NAD{sup +}) and the biopolymer chitosan (CHIT) were drop-coated onto the surface of the transducer (MB-SPCE) in a simple one step fabrication process. The reagentless biosensor was used with amperometry in stirred solution at an applied potential of +0.1 V (vs. Ag/AgCl). All experiments were carried out at the following conditions: pH 7, temperature 37 °C, atmosphere 5% CO{sub 2}. The linear range of the device was found to be 25–125 μM in phosphate buffer (75 mM, containing 0.05 M NaCl) and 25–150 μM in cell culture medium. The limits of detection (LOD) were found to be 1.2 μM and 4.2 μM based on three times signal to noise, using PBS and culture medium respectively. The sensitivity was calculated to be 106 nA μM{sup −1} cm{sup −2} and 210 nA μM{sup −1} cm{sup −2} in PBS and cell medium respectively. The response time was ∼60 s in an agitated solution. HepG2 cells were exposed to various concentrations of paracetamol (1 mM, 5 mM and 10 mM) in order to investigate the drug-induced release of glutamate into the culture medium in real time. Two toxicity studies were investigated using different methods of exposure and analysis. The first method consisted of a single measurement of the glutamate concentration, using the method of standard addition, after 24 h incubation. The concentrations of glutamate were found to be 52 μM, 93 μM and 177 μM, released on exposure to 1 mM, 5 mM and 10 mM paracetamol respectively. The second method involved the

  17. A novel reagentless glutamate microband biosensor for real-time cell toxicity monitoring

    International Nuclear Information System (INIS)

    Hughes, G.; Pemberton, R.M.; Fielden, P.R.; Hart, J.P.

    2016-01-01

    A reagentless glutamate biosensor was applied to the determination of glutamate released from liver hepatocellular carcinoma cells (HepG2) in response to toxic challenge from various concentrations of paracetamol. A screen printed carbon electrode (SPCE) containing the electrocatalyst Meldola's Blue (MB-SPCE) served as the electron mediator for the oxidation of NADH. A mixture of the enzyme glutamate dehydrogenase (GLDH), cofactor nicotinamide adenine dinucleotide (NAD"+) and the biopolymer chitosan (CHIT) were drop-coated onto the surface of the transducer (MB-SPCE) in a simple one step fabrication process. The reagentless biosensor was used with amperometry in stirred solution at an applied potential of +0.1 V (vs. Ag/AgCl). All experiments were carried out at the following conditions: pH 7, temperature 37 °C, atmosphere 5% CO_2. The linear range of the device was found to be 25–125 μM in phosphate buffer (75 mM, containing 0.05 M NaCl) and 25–150 μM in cell culture medium. The limits of detection (LOD) were found to be 1.2 μM and 4.2 μM based on three times signal to noise, using PBS and culture medium respectively. The sensitivity was calculated to be 106 nA μM"−"1 cm"−"2 and 210 nA μM"−"1 cm"−"2 in PBS and cell medium respectively. The response time was ∼60 s in an agitated solution. HepG2 cells were exposed to various concentrations of paracetamol (1 mM, 5 mM and 10 mM) in order to investigate the drug-induced release of glutamate into the culture medium in real time. Two toxicity studies were investigated using different methods of exposure and analysis. The first method consisted of a single measurement of the glutamate concentration, using the method of standard addition, after 24 h incubation. The concentrations of glutamate were found to be 52 μM, 93 μM and 177 μM, released on exposure to 1 mM, 5 mM and 10 mM paracetamol respectively. The second method involved the continuous monitoring of glutamate

  18. Independent and additive effects of glutamic acid and methionine on yeast longevity.

    Science.gov (United States)

    Wu, Ziyun; Song, Lixia; Liu, Shao Quan; Huang, Dejian

    2013-01-01

    It is established that glucose restriction extends yeast chronological and replicative lifespan, but little is known about the influence of amino acids on yeast lifespan, although some amino acids were reported to delay aging in rodents. Here we show that amino acid composition greatly alters yeast chronological lifespan. We found that non-essential amino acids (to yeast) methionine and glutamic acid had the most significant impact on yeast chronological lifespan extension, restriction of methionine and/or increase of glutamic acid led to longevity that was not the result of low acetic acid production and acidification in aging media. Remarkably, low methionine, high glutamic acid and glucose restriction additively and independently extended yeast lifespan, which could not be further extended by buffering the medium (pH 6.0). Our preliminary findings using yeasts with gene deletion demonstrate that glutamic acid addition, methionine and glucose restriction prompt yeast longevity through distinct mechanisms. This study may help to fill a gap in yeast model for the fast developing view that nutrient balance is a critical factor to extend lifespan.

  19. Cell Death-Autophagy Loop and Glutamate-Glutamine Cycle in Amyotrophic Lateral Sclerosis

    Directory of Open Access Journals (Sweden)

    Shu Yuan

    2017-07-01

    Full Text Available Although we know that amyotrophic lateral sclerosis (ALS is correlated with the glutamate-mediated corticomotor neuronal hyperexcitability, detailed ALS pathology remains largely unexplained. While a number of drugs have been developed, no cure exists so far. Here, we propose a hypothesis of neuronal cell death—incomplete autophagy positive-feedback loop—and summarize the role of the neuron-astrocyte glutamate-glutamine cycle in ALS. The disruption of these two cycles might ideally retard ALS progression. Cerebrovascular injuries (such as multiple embolization sessions and strokes induce neuronal cell death and the subsequent autophagy. ALS impairs autophagosome-lysosome fusion and leads to magnified cell death. Trehalose rescues this impaired fusion step, significantly delaying the onset of the disease, although it does not affect the duration of the disease. Therefore, trehalose might be a prophylactic drug for ALS. Given that a major part of neuronal glutamate is converted from glutamine through neuronal glutaminase (GA, GA inhibitors may decrease the neuronal glutamate accumulation, and, therefore, might be therapeutic ALS drugs. Of these, Ebselen is the most promising one with strong antioxidant properties.

  20. Experiments on Pool-riffle Sequences with Multi-fractional Sediment Bed During Floods

    Science.gov (United States)

    Rodriguez, J. F.; Vahidi, E.; Bayat, E.; de Almeida, G. A. M.; Saco, P. M.

    2017-12-01

    The morphodynamics of pools and riffles has been the subject of research for over a century and has more recently attracted intense attention for their central role in providing habitat diversity conditions, both in terms of flow and substrate. Initial efforts to explain the long-term stability of the pool-riffle (PR) sequences (often referred to as self-maintenance) focused almost exclusively on cross sectional flow characteristics (either average or near bed velocity or shear stress), using episodic shifts in higher shear stress or velocities from riffles to pools during floods (i.e. reversal conditions) as an indication of the long-term self-maintenance of the structures.. However, less attention has been paid to the interactions of flow unsteadiness, sediment supply and sedimentological contrasts as the drivers for maintaining PR sequences. Here we investigate these effects through laboratory experiments on a scaled-down PR sequence of an existing gravel bed river. Froude similitude and equality of Shields' number were applied to scale one- to four-year recurrence flood events and sediment size distributions, respectively. We conducted experiments with different hydrographs and different sedimentological conditions. In each experiment we continuously measured velocities and shear stresses (using acoustic velocity profilers) bed levels (using a bed profiler) and bed grain size distribution (using an automatic digital technique on the painted bed sediments) during the hydrographs. Our results show that the most important factors for self-maintenance were the sediment bed composition, the level of infilling of the pool and the sediment supply grainsize distribution. These results highlight the need to consider the time varying sedimentological characteristics of a PR sequence to assess its capacity for self-maintenance.

  1. 76 FR 62605 - Virginia Graeme Baker Pool and Spa Safety Act; Interpretation of Unblockable Drain

    Science.gov (United States)

    2011-10-11

    ... the VGB Act defines an ``unblockable drain'' as ``a drain of any size and shape that a human body... intentions. They claim that for this reason, backup systems are necessary, and a swimming pool or spa with a... of an ``unblockable drain,'' at 16 CFR 1450.2(b) and believe it was in error. Regardless of the size...

  2. Optimum allocation of imaging time and minimum detectable activity in dual isotope blood pool subtraction indium-111 platelet imaging

    International Nuclear Information System (INIS)

    Machac, J.; Horowitz, S.F.; Goldsmith, S.J.; Fuster, V.

    1984-01-01

    Indium-111 labeled platelet imaging is a tool for detection of thrombus formation in vascular spaces. Dual isotope blood pool subtraction may help differentiate focal platelet accumulation from blood pool activity. This study used a computer model to calculate the minimum excess-to-blood pool platelet ratio (EX/BP) and the optimum dual isotope imaging times under varied conditions of lesion size. The model simulated usual human imaging doses of 500 μCi of In-111 platelets and 5mCi of Tc-99m labeled RBCs giving a reference cardiac blood pool region (100cc) of 10000 cpm for Tc-99m and 500 cpm for In-111. The total imaging time was fixed at 20 minutes, while the two isotope imaging times (TIn/TTc) were varied, as were the simulated lesion size (cc) and EX/BP. The relative error of the excess counts was calculated using propagation of error theory. At the critical level of detection, where the excess lesion counts equal 3 times the standard deviation, the optimum TIn/TTc and minimum Ex/BP were determined for each lesion size. For the smallest lesion size (0.1cc), the minimum detectable EX/BP ratio was 1.6, with the best TIn/TTC ratio of 18/2 minutes, and for large lesions, an EX/BP of 0.1, with a TIn/TTc of 16/4. This model provides an estimate of the sensitivity and optimizes imaging times in dual isotope subtraction platelet imaging. The model is adaptable to varying isotope doses, total imaging times and lesion size. This information will be helpful in future in- vivo imaging studies of intravascular thrombi in humans

  3. Glutamate/GABA+ ratio is associated with the psychosocial domain of autistic and schizotypal traits.

    Directory of Open Access Journals (Sweden)

    Talitha C Ford

    Full Text Available The autism and schizophrenia spectra overlap to a large degree in the social and interpersonal domains. Similarly, abnormal excitatory glutamate and inhibitory γ-aminobutyric acid (GABA neurotransmitter concentrations have been reported for both spectra, with the interplay of these neurotransmitters important for cortical excitation to inhibition regulation. This study investigates whether these neurotransmitter abnormalities are specific to the shared symptomatology, and whether the degree of abnormality increases with increasing symptom severity. Hence, the relationship between the glutamate/GABA ratio and autism and schizophrenia spectrum traits in an unmedicated, subclinical population was investigated.A total of 37 adults (19 female, 18 male aged 18-38 years completed the Autism Spectrum Quotient (AQ and Schizotypal Personality Questionnaire (SPQ, and participated in the resting state proton magnetic resonance spectroscopy study in which sequences specific for quantification of glutamate and GABA+ concentration were applied to a right and left superior temporal voxel.There were significant, moderate, positive relationships between right superior temporal glutamate/GABA+ ratio and AQ, SPQ and AQ+SPQ total scores (p<0.05, SPQ subscales Social Anxiety, No Close Friend, Constricted Affect, Odd Behaviour, Odd Speech, Ideas of Reference and Suspiciousness, and AQ subscales Social Skills, Communication and Attention Switching (p<0.05; increased glutamate/GABA+ coinciding with higher scores on these subscales. Only the relationships between glutamate/GABA+ ratio and Social Anxiety, Constricted Affect, Social Skills and Communication survived multiple comparison correction (p< 0.004. Left superior temporal glutamate/GABA+ ratio reduced with increasing restricted imagination (p<0.05.These findings demonstrate evidence for an association between excitatory/inhibitory neurotransmitter concentrations and symptoms that are shared between the autism and

  4. SIRT1-mediated deacetylation of PGC1α attributes to the protection of curcumin against glutamate excitotoxicity in cortical neurons

    International Nuclear Information System (INIS)

    Jia, Ning; Sun, Qinru; Su, Qian; Chen, Guomin

    2016-01-01

    It is widely accepted that accumulation of extracellular glutamate mediates neuronal injuries in a number of neurological disorders via binding glutamate receptors. However, usage of the glutamate receptor antagonists aimed to prevent glutamate excitotoxicity is still controversial. As a polyphenol natural product, curcumin, has been implied multiple bioactivities. In this study, we explored whether the silent information regulator 1 (SIRT1)-peroxisome proliferator-activated receptor-coactivator 1α (PGC1α) pathway participated in the protection of curcumin against glutamate excitotoxicity. The cultured primary cortical neurons were treated with glutamate to set up a neuronal excitotoxicity model. The MTT and TUNEL methods were employed to measure cell viability and apoptosis, respectively. The mitochondrial function, the expression levels of SIRT1, PGC1α and acetylated PGC1α (ac-PGC1α) were measured to explore the mechanism of curcumin against glutamate excitotoxicity. The results showed that glutamate significantly induced cell death and apoptosis, which was blocked by pretreatment with curcumin. Meanwhile, curcumin preserved mitochondrial function, increased the expression level of SIRT1 and reduced the level of ac-PGC1α in the presence of glutamate. These results suggest that SIRT1-mediated deacetylation of PGC1α attributes to the neuroprotection of curcumin against glutamate excitotoxicity. - Highlights: • Curcumin attenuates glutamate induced cell death and apoptosis in cultured neurons. • Curcumin preserves mitochondrial function in the presence of glutamate. • Curcumin enhanced the expression of SIRT1 in the glutamate rich environment. • SIRT1-mediated deacetylation of PGC1α attributes to the neuroprotection of curcumin.

  5. Self-Assembled Nanomicelles as MRI Blood-Pool Contrast Agent.

    Science.gov (United States)

    Babič, Andrej; Vorobiev, Vassily; Xayaphoummine, Céline; Lapicorey, Gaëlle; Chauvin, Anne-Sophie; Helm, Lothar; Allémann, Eric

    2018-01-26

    Gadolinium-loaded nanomicelles show promise as future magnetic resonance imaging (MRI) contrast agents (CAs). Their increased size and high gadolinium (Gd) loading gives them an edge in proton relaxivity over smaller molecular Gd-complexes. Their size and stealth properties are fundamental for their long blood residence time, opening the possibility for use as blood-pool contrast agents. Using l-tyrosine as a three-functional scaffold we synthesized a nanostructure building block 8. The double C18 aliphatic chain on one side, Gd-1,4,7,10-tetraazacyclododecane-1-4-7-triacetic acid (Gd-DO3A) with access to bulk water in the center and 2 kDa PEG on the hydrophilic side gave the amphiphilic properties required for the core-shell nanomicellar architecture. The self-assembly into Gd-loaded monodispersed 10-20 nm nanomicelles occurred spontaneously in water. These nanomicelles (Tyr-MRI) display very high relaxivity at 29 mm -1  s -1 at low field strength and low cytotoxicity. Good contrast enhancement of the blood vessels and the heart together with prolonged circulation time in vivo, makes Tyr-MRI an excellent candidate for a new supramolecular blood-pool MRI CA. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Changes in medium radioactivity and composition accompany high-affinity uptake of glutamate and aspartate by mouse brain slices

    International Nuclear Information System (INIS)

    Latzkovits, L.; Neidle, A.; Lajtha, A.

    1984-01-01

    In measurements of high affinity transport in tissue slices, the incubation medium is often treated as an ''infinitely large pool''. External substrate concentrations, even at the micromolar level, are assumed to be constant and metabolic interactions between tissue and medium are neglected. In the present report we describe experiments in which glutamic and aspartic acid uptake by mouse brain slices were studied using techniques that could test these assumptions. Cerebral hemispheres were cut into 0.1 mm sections and about 90 mg of tissue incubated in 10 ml of oxygenated medium. After 45 minutes of equilibration, radioactive substrates were added and the concentrations and specific activities of the amino acids and their metabolites in the medium were determined. During the first 10 min following substrate addition, rapid decreases in glutamic and aspartic acid concentrations in the medium were accompanied by large decreases in specific activity caused by the continuous release of these amino acids from the tissue. In addition, extensive conversion of both substrates to glutamine and the preferential accumulation of this metabolite, in the medium, was found. These results demonstrate that metabolism and release occur simultaneously with uptake during transport experiments in vitro and that these processes can take place in specific tissue compartments. It is therefore necessary to measure the tissue and medium concentration levels of amino acids along with their radioactivity in such experiments, since all three processes (transport, metabolism, and compartmentation) are interrelated in the clearance of amino acids from the incubation medium and probably from the extracellular spaces in vivo as well

  7. Glutamate transporter type 3 knockout leads to decreased heart rate possibly via parasympathetic mechanism

    OpenAIRE

    Deng, Jiao; Li, Jiejie; Li, Liaoliao; Feng, Chenzhuo; Xiong, Lize; Zuo, Zhiyi

    2013-01-01

    Parasympathetic tone is a dominant neural regulator for basal heart rate. Glutamate transporters (EAAT) via their glutamate uptake functions regulate glutamate neurotransmission in the central nervous system. We showed that EAAT type 3 (EAAT3) knockout mice had a slower heart rate than wild-type mice when they were anesthetized. We design this study to determine whether non-anesthetized EAAT3 knockout mice have a slower heart rate and, if so, what may be the mechanism for this effect. Young a...

  8. Fuzzy pool balance: An algorithm to achieve a two dimensional balance in distribute storage systems

    International Nuclear Information System (INIS)

    Wu, Wenjing; Chen, Gang

    2014-01-01

    The limitation of scheduling modules and the gradual addition of disk pools in distributed storage systems often result in imbalances among their disk pools in terms of both disk usage and file count. This can cause various problems to the storage system such as single point of failure, low system throughput and imbalanced resource utilization and system loads. An algorithm named Fuzzy Pool Balance (FPB) is proposed here to solve this problem. The input of FPB is the current file distribution among disk pools and the output is a file migration plan indicating what files are to be migrated to which pools. FPB uses an array to classify the files by their sizes. The file classification array is dynamically calculated with a defined threshold named T max that defines the allowed pool disk usage deviations. File classification is the basis of file migration. FPB also defines the Immigration Pool (IP) and Emigration Pool (EP) according to the pool disk usage and File Quantity Ratio (FQR) that indicates the percentage of each category of files in each disk pool, so files with higher FQR in an EP will be migrated to IP(s) with a lower FQR of this file category. To verify this algorithm, we implemented FPB on an ATLAS Tier2 dCache production system. The results show that FPB can achieve a very good balance in both free space and file counts, and adjusting the threshold value T max and the correction factor to the average FQR can achieve a tradeoff between free space and file count.

  9. Properties of glutamate-gated ion channels in horizontal cells of the perch retina.

    Science.gov (United States)

    Schmidt, K F

    1997-08-01

    The effect of two different concentrations of L-glutamate and kainate on the gating kinetics of amino acid-sensitive non-NMDA channels were studied in cultured teleost retinal horizontal cells by single-channel recording and by noise analysis of whole-cell currents. When the glutamate agonist kainate was applied clearly parabolic mean-variance relations of whole-cell membrane currents (up to 3000 pA) indicated that this agonist was acting on one type of channels with a conductance of 5-10 pS. The cells were less sensitive when L-glutamate was used as the agonist and in most cases whole-cell currents amounted to less than 200 pA. The mean-variance relation of glutamate induced currents was complex, indicating that more than one type of channel opening could be involved. Power spectra of whole-cell currents were fitted with two Lorentzians with time constants of approx. 1 and 5-20 msec. Effects on amplitudes and time constants of agonist concentrations are demonstrated. Two categories of unitary events with mean open times of approx. 1 and 7 msec and conductances of approx. 7 and 12 pS, respectively, were obtained in single-channel recordings from cell-attached patches at different concentrations of glutamate in the pipette.

  10. Glutamic acid promotes monacolin K production and monacolin K biosynthetic gene cluster expression in Monascus.

    Science.gov (United States)

    Zhang, Chan; Liang, Jian; Yang, Le; Chai, Shiyuan; Zhang, Chenxi; Sun, Baoguo; Wang, Chengtao

    2017-12-01

    This study investigated the effects of glutamic acid on production of monacolin K and expression of the monacolin K biosynthetic gene cluster. When Monascus M1 was grown in glutamic medium instead of in the original medium, monacolin K production increased from 48.4 to 215.4 mg l -1 , monacolin K production increased by 3.5 times. Glutamic acid enhanced monacolin K production by upregulating the expression of mokB-mokI; on day 8, the expression level of mokA tended to decrease by Reverse Transcription-polymerase Chain Reaction. Our findings demonstrated that mokA was not a key gene responsible for the quantity of monacolin K production in the presence of glutamic acid. Observation of Monascus mycelium morphology using Scanning Electron Microscope showed glutamic acid significantly increased the content of Monascus mycelium, altered the permeability of Monascus mycelium, enhanced secretion of monacolin K from the cell, and reduced the monacolin K content in Monascus mycelium, thereby enhancing monacolin K production.

  11. The neuroprotective effects of tocotrienol rich fraction and alpha tocopherol against glutamate injury in astrocytes

    Directory of Open Access Journals (Sweden)

    Thilaga Rati Selvaraju

    2014-11-01

    Full Text Available Tocotrienol rich fraction (TRF is an extract of palm oil, which consists of 25% alpha tocopherol (α-TCP and 75% tocotrienols. TRF has been shown to possess potent antioxidant, anti-inflammatory, anticancer, neuroprotection, and cholesterol lowering activities. Glutamate is the main excitatory amino acid neurotransmitter in the central nervous system of mammalian, which can be excitotoxic, and it has been suggested to play a key role in neurodegenerative disorders like Parkinson’s and Alzheimer’s diseases. In this present study, the effects of vitamin E (TRF and α-TCP in protecting astrocytes against glutamate injury were elucidated. Astrocytes induced with 180 mM of glutamate lead to significant cell death. However, glutamate mediated cytotoxicity was diminished via pre and post supplementation of TRF and α-TCP. Hence, vitamin E acted as a potent antioxidant agent in recovering mitochondrial injury due to elevated oxidative stress, and enhanced better survivability upon glutamate toxicity.  

  12. Determination of glutamine and glutamic acid in mammalian cell cultures using tetrathiafulvalene modified enzyme electrodes.

    Science.gov (United States)

    Mulchandani, A; Bassi, A S

    1996-01-01

    Tetrathiafulvalene (TTF) mediated amperometric enzyme electrodes have been developed for the monitoring of L-glutamine and L-glutamic acid in growing mammalian cell cultures. The detection of glutamine was accomplished by a coupled enzyme system comprised of glutaminase plus glutamate oxidase, while the detection of glutamic acid was carried out by a single enzyme, glutamate oxidase. The appropriate enzyme(s) were immoblized on the Triton-X treated surface of tetrathiafulvalene modified carbon paste electrodes by adsorption, in conjunction with entrapment by an electrochemically deposited copolymer film of 1,3-phenylenediamine and resorcinol. Operating conditions for the glutamine enzyme electrode were optimized with respect to the amount of enzymes immoblized, pH, temperature and mobile phase flow rate for operation in a flow injection (FIA) system. When applied to glutamine and glutamic acid measurements in mammalian cell culture in FIA, the results obtained with enzyme electrodes were in excellent agreement with those determined by enzymatic analysis.

  13. Distribution of radiolabeled L-glutamate and D-aspartate from blood into peripheral tissues in naive rats: Significance for brain neuroprotection

    International Nuclear Information System (INIS)

    Klin, Yael; Zlotnik, Alexander; Boyko, Matthew; Ohayon, Sharon; Shapira, Yoram; Teichberg, Vivian I.

    2010-01-01

    Research highlights: → Blood glutamate has a half-life time of 2-3 min. → Blood glutamate is submitted to rapid decarboxylation. → Blood glutamate and its metabolites are mainly absorbed in skeletal muscle and liver. → The skeletal muscle and liver are now targets for potential drugs affording brain neuroprotection. -- Abstract: Excess L-glutamate (glutamate) levels in brain interstitial and cerebrospinal fluids (ISF and CSF, respectively) are the hallmark of several neurodegenerative conditions such as stroke, traumatic brain injury or amyotrophic lateral sclerosis. Its removal could prevent the glutamate excitotoxicity that causes long-lasting neurological deficits. As in previous studies, we have established the role of blood glutamate levels in brain neuroprotection, we have now investigated the contribution of the peripheral organs to the homeostasis of glutamate in blood. We have administered naive rats with intravenous injections of either L-[1- 14 C] Glutamic acid (L-[1- 14 C] Glu), L-[G- 3 H] Glutamic acid (L-[G- 3 H] Glu) or D-[2,3- 3 H] Aspartic acid (D-[2,3- 3 H] Asp), a non-metabolized analog of glutamate, and have followed their distribution into peripheral organs. We have observed that the decay of the radioactivity associated with L-[1- 14 C] Glu and L-[G- 3 H] Glu was faster than that associated with glutamate non-metabolized analog, D-[2,3- 3 H] Asp. L-[1- 14 C] Glu was subjected in blood to a rapid decarboxylation with the loss of 14 CO 2 . The three major sequestrating organs, serving as depots for the eliminated glutamate and/or its metabolites were skeletal muscle, liver and gut, contributing together 92% or 87% of total L-[U- 14 C] Glu or D-[2,3- 3 H] Asp radioactivity capture. L-[U- 14 C] Glu and D-[2,3- 3 H] Asp showed a different organ sequestration pattern. We conclude that glutamate is rapidly eliminated from the blood into peripheral tissues, mainly in non-metabolized form. The liver plays a central role in glutamate metabolism

  14. Distribution of radiolabeled L-glutamate and D-aspartate from blood into peripheral tissues in naive rats: Significance for brain neuroprotection

    Energy Technology Data Exchange (ETDEWEB)

    Klin, Yael [Department of Neurobiology, The Weizmann Institute of Science, Rehovot 76100 (Israel); Zlotnik, Alexander; Boyko, Matthew; Ohayon, Sharon; Shapira, Yoram [The Division of Anesthesiology, Soroka Medical Center and Ben Gurion University of the Negev, Beer-Sheva (Israel); Teichberg, Vivian I., E-mail: Vivian.teichberg@weizmann.ac.il [Department of Neurobiology, The Weizmann Institute of Science, Rehovot 76100 (Israel)

    2010-09-03

    Research highlights: {yields} Blood glutamate has a half-life time of 2-3 min. {yields} Blood glutamate is submitted to rapid decarboxylation. {yields} Blood glutamate and its metabolites are mainly absorbed in skeletal muscle and liver. {yields} The skeletal muscle and liver are now targets for potential drugs affording brain neuroprotection. -- Abstract: Excess L-glutamate (glutamate) levels in brain interstitial and cerebrospinal fluids (ISF and CSF, respectively) are the hallmark of several neurodegenerative conditions such as stroke, traumatic brain injury or amyotrophic lateral sclerosis. Its removal could prevent the glutamate excitotoxicity that causes long-lasting neurological deficits. As in previous studies, we have established the role of blood glutamate levels in brain neuroprotection, we have now investigated the contribution of the peripheral organs to the homeostasis of glutamate in blood. We have administered naive rats with intravenous injections of either L-[1-{sup 14}C] Glutamic acid (L-[1-{sup 14}C] Glu), L-[G-{sup 3}H] Glutamic acid (L-[G-{sup 3}H] Glu) or D-[2,3-{sup 3}H] Aspartic acid (D-[2,3-{sup 3}H] Asp), a non-metabolized analog of glutamate, and have followed their distribution into peripheral organs. We have observed that the decay of the radioactivity associated with L-[1-{sup 14}C] Glu and L-[G-{sup 3}H] Glu was faster than that associated with glutamate non-metabolized analog, D-[2,3-{sup 3}H] Asp. L-[1-{sup 14}C] Glu was subjected in blood to a rapid decarboxylation with the loss of {sup 14}CO{sub 2}. The three major sequestrating organs, serving as depots for the eliminated glutamate and/or its metabolites were skeletal muscle, liver and gut, contributing together 92% or 87% of total L-[U-{sup 14}C] Glu or D-[2,3-{sup 3}H] Asp radioactivity capture. L-[U-{sup 14}C] Glu and D-[2,3-{sup 3}H] Asp showed a different organ sequestration pattern. We conclude that glutamate is rapidly eliminated from the blood into peripheral tissues

  15. Disease-specific monoclonal antibodies targeting glutamate decarboxylase impair GABAergic neurotransmission and affect motor learning and behavioral functions

    Directory of Open Access Journals (Sweden)

    Mario U Manto

    2015-03-01

    Full Text Available Autoantibodies to the smaller isoform of glutamate decarboxylase can be found in patients with type 1 diabetes and a number of neurological disorders, including stiff-person syndrome, cerebellar ataxia and limbic encephalitis. The detection of disease-specific autoantibody epitopes led to the hypothesis that distinct glutamate decarboxylase autoantibodies may elicit specific neurological phenotypes. We explored the in vitro/in vivo effects of well-characterized monoclonal glutamate decarboxylase antibodies. We found that glutamate decarboxylase autoantibodies present in patients with stiff person syndrome (n = 7 and cerebellar ataxia (n = 15 recognized an epitope distinct from that recognized by glutamate decarboxylase autoantibodies present in patients with type 1 diabetes mellitus (n = 10 or limbic encephalitis (n = 4. We demonstrated that the administration of a monoclonal glutamate decarboxylase antibody representing this epitope specificity (1 disrupted in vitro the association of glutamate decarboxylase with γ-Aminobutyric acid containing synaptic vesicles, (2 depressed the inhibitory synaptic transmission in cerebellar slices with a gradual time course and a lasting suppressive effect, (3 significantly decreased conditioned eyelid responses evoked in mice, with no modification of learning curves in the classical eyeblink-conditioning task, (4 markedly impaired the facilitatory effect exerted by the premotor cortex over the motor cortex in a paired-pulse stimulation paradigm, and (5 induced decreased exploratory behavior and impaired locomotor function in rats. These findings support the specific targeting of glutamate decarboxylase by its autoantibodies in the pathogenesis of stiff-person syndrome and cerebellar ataxia. Therapies of these disorders based on selective removal of such glutamate decarboxylase antibodies could be envisioned.

  16. A new pooling strategy for high-throughput screening: the Shifted Transversal Design

    Directory of Open Access Journals (Sweden)

    Thierry-Mieg Nicolas

    2006-01-01

    Full Text Available Abstract Background In binary high-throughput screening projects where the goal is the identification of low-frequency events, beyond the obvious issue of efficiency, false positives and false negatives are a major concern. Pooling constitutes a natural solution: it reduces the number of tests, while providing critical duplication of the individual experiments, thereby correcting for experimental noise. The main difficulty consists in designing the pools in a manner that is both efficient and robust: few pools should be necessary to correct the errors and identify the positives, yet the experiment should not be too vulnerable to biological shakiness. For example, some information should still be obtained even if there are slightly more positives or errors than expected. This is known as the group testing problem, or pooling problem. Results In this paper, we present a new non-adaptive combinatorial pooling design: the "shifted transversal design" (STD. It relies on arithmetics, and rests on two intuitive ideas: minimizing the co-occurrence of objects, and constructing pools of constant-sized intersections. We prove that it allows unambiguous decoding of noisy experimental observations. This design is highly flexible, and can be tailored to function robustly in a wide range of experimental settings (i.e., numbers of objects, fractions of positives, and expected error-rates. Furthermore, we show that our design compares favorably, in terms of efficiency, to the previously described non-adaptive combinatorial pooling designs. Conclusion This method is currently being validated by field-testing in the context of yeast-two-hybrid interactome mapping, in collaboration with Marc Vidal's lab at the Dana Farber Cancer Institute. Many similar projects could benefit from using the Shifted Transversal Design.

  17. Optimal Sizing and Sitting of Smart Microgrid Units under Pool Electricity Market

    DEFF Research Database (Denmark)

    Hakimi, Seyed Mehdi; Hajizadeh, Amin

    2017-01-01

    , reliability cost, power loss cost and selling and buying electricity cost. The new idea of this paper is the investigation of pool electricity market aspects in optimization of smart microgrid. On the other hand, cost minimization of smart microgrid is related to their bidding strategies. Therefore two...... different optimization tools are considered. First, a game-theoretical (GT) model has been used for bidding strategy of smart microgrid as a price-maker, in a long-term electricity market. Secondly, a particle swarm optimization (PSO) algorithm is employed to obtain the best cost value of smart microgrids...... construction. This study was performed for the Ekbatan residential complex in Tehran, Iran. It has three smart microgrids consist of renewable energy resources. They participate in a long-term electricity market as a price maker. The results show that the proposed method is more effective and has lower cost...

  18. Traumatic Brain Injury Increases Cortical Glutamate Network Activity by Compromising GABAergic Control.

    Science.gov (United States)

    Cantu, David; Walker, Kendall; Andresen, Lauren; Taylor-Weiner, Amaro; Hampton, David; Tesco, Giuseppina; Dulla, Chris G

    2015-08-01

    Traumatic brain injury (TBI) is a major risk factor for developing pharmaco-resistant epilepsy. Although disruptions in brain circuitry are associated with TBI, the precise mechanisms by which brain injury leads to epileptiform network activity is unknown. Using controlled cortical impact (CCI) as a model of TBI, we examined how cortical excitability and glutamatergic signaling was altered following injury. We optically mapped cortical glutamate signaling using FRET-based glutamate biosensors, while simultaneously recording cortical field potentials in acute brain slices 2-4 weeks following CCI. Cortical electrical stimulation evoked polyphasic, epileptiform field potentials and disrupted the input-output relationship in deep layers of CCI-injured cortex. High-speed glutamate biosensor imaging showed that glutamate signaling was significantly increased in the injured cortex. Elevated glutamate responses correlated with epileptiform activity, were highest directly adjacent to the injury, and spread via deep cortical layers. Immunoreactivity for markers of GABAergic interneurons were significantly decreased throughout CCI cortex. Lastly, spontaneous inhibitory postsynaptic current frequency decreased and spontaneous excitatory postsynaptic current increased after CCI injury. Our results suggest that specific cortical neuronal microcircuits may initiate and facilitate the spread of epileptiform activity following TBI. Increased glutamatergic signaling due to loss of GABAergic control may provide a mechanism by which TBI can give rise to post-traumatic epilepsy. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  19. Techno-economic assessment of the production of bio-based chemicals from glutamic acid

    NARCIS (Netherlands)

    Lammens, T.M.; Gangarapu, S.; Franssen, M.C.R.; Scott, E.L.; Sanders, J.P.M.

    2012-01-01

    In this review, possible process steps for the production of bio-based industrial chemicals from glutamic acid are described, including a techno-economic assessment of all processes. The products under investigation were those that were shown to be synthesized from glutamic acid on lab-scale, namely

  20. Chin Shan analyses show advantages of whole pool multi-rack approach

    International Nuclear Information System (INIS)

    Singh, K.P.; Soler, A.I.

    1991-01-01

    Nuclear fuel storage racks are essentially thin-walled, cellular structures of prismatic cross-section. Although the details of design vary from one supplier to another, certain key physical attributes are common to all designs. For example, all racks feature square cells of sufficient opening size and height to enable insertion and withdrawal of the fuel assembly. The array of cells is positioned in a vertical orientation and is supported off the pool slab surface by four or more support legs. The spent fuel pool is filled with the individual fuel racks. The plenum created by the support legs is essential for proper cooling of the fuel assemblies stored in the rack, which relies on natural convective cooling to extract the heat emitted by the spent fuel. However, it has the insalutary effect of making it kinematically less stable. Regulatory authorities require careful and comprehensive analysis of the response of the racks under the seismic motions postulated for the pool slab. Results from whole pool multi-rack (WPMR) analyses at the Chin Shan and Oyster Creek nuclear plants point up the potential inadequacies of single rack 3D analyses, and show just how important it is to carry out WPMR simulations, despite their abstruseness and high cost. (author)

  1. Design of hydrotherapy exercise pools.

    Science.gov (United States)

    Edlich, R F; Abidin, M R; Becker, D G; Pavlovich, L J; Dang, M T

    1988-01-01

    Several hydrotherapy pools have been designed specifically for a variety of aquatic exercise. Aqua-Ark positions the exerciser in the center of the pool for deep-water exercise. Aqua-Trex is a shallow underwater treadmill system for water walking or jogging. Swim-Ex generates an adjustable laminar flow that permits swimming without turning. Musculoskeletal conditioning can be accomplished in the above-ground Arjo shallow-water exercise pool. A hydrotherapy pool also can be custom designed for musculoskeletal conditioning in its shallow part and cardiovascular conditioning in a deeper portion of the pool. Regardless of the type of exercise, there is general agreement that the specific exercise conducted in water requires significantly more energy expenditure than when the same exercise is performed on land.

  2. Vulnerability to glutamate toxicity of dopaminergic neurons is dependent on endogenous dopamine and MAPK activation.

    Science.gov (United States)

    Izumi, Yasuhiko; Yamamoto, Noriyuki; Matsuo, Takaaki; Wakita, Seiko; Takeuchi, Hiroki; Kume, Toshiaki; Katsuki, Hiroshi; Sawada, Hideyuki; Akaike, Akinori

    2009-07-01

    Dopaminergic neurons are more vulnerable than other types of neurons in cases of Parkinson disease and ischemic brain disease. An increasing amount of evidence suggests that endogenous dopamine plays a role in the vulnerability of dopaminergic neurons. Although glutamate toxicity contributes to the pathogenesis of these disorders, the sensitivity of dopaminergic neurons to glutamate toxicity has not been clarified. In this study, we demonstrated that dopaminergic neurons were preferentially affected by glutamate toxicity in rat mesencephalic cultures. Glutamate toxicity in dopaminergic neurons was blocked by inhibiting extracellular signal-regulated kinase (ERK), c-jun N-terminal kinase, and p38 MAPK. Furthermore, depletion of dopamine by alpha-methyl-dl-p-tyrosine methyl ester (alpha-MT), an inhibitor of tyrosine hydroxylase (TH), protected dopaminergic neurons from the neurotoxicity. Exposure to glutamate facilitated phosphoryration of TH at Ser31 by ERK, which contributes to the increased TH activity. Inhibition of ERK had no additive effect on the protection offered by alpha-MT, whereas alpha-MT and c-jun N-terminal kinase or p38 MAPK inhibitors had additive effects and yielded full protection. These data suggest that endogenous dopamine is responsible for the vulnerability to glutamate toxicity of dopaminergic neurons and one of the mechanisms may be an enhancement of dopamine synthesis mediated by ERK.

  3. Improvement of sampling plans for Salmonella detection in pooled table eggs by use of real-time PCR.

    Science.gov (United States)

    Pasquali, Frédérique; De Cesare, Alessandra; Valero, Antonio; Olsen, John Emerdhal; Manfreda, Gerardo

    2014-08-01

    Eggs and egg products have been described as the most critical food vehicles of salmonellosis. The prevalence and level of contamination of Salmonella on table eggs are low, which severely affects the sensitivity of sampling plans applied voluntarily in some European countries, where one to five pools of 10 eggs are tested by the culture based reference method ISO 6579:2004. In the current study we have compared the testing-sensitivity of the reference culture method ISO 6579:2004 and an alternative real-time PCR method on Salmonella contaminated egg-pool of different sizes (4-9 uninfected eggs mixed with one contaminated egg) and contamination levels (10°-10(1), 10(1)-10(2), 10(2)-10(3)CFU/eggshell). Two hundred and seventy samples corresponding to 15 replicates per pool size and inoculum level were tested. At the lowest contamination level real-time PCR detected Salmonella in 40% of contaminated pools vs 12% using ISO 6579. The results were used to estimate the lowest number of sample units needed to be tested in order to have a 95% certainty not falsely to accept a contaminated lot by Monte Carlo simulation. According to this simulation, at least 16 pools of 10 eggs each are needed to be tested by ISO 6579 in order to obtain this confidence level, while the minimum number of pools to be tested was reduced to 8 pools of 9 eggs each, when real-time PCR was applied as analytical method. This result underlines the importance of including analytical methods with higher sensitivity in order to improve the efficiency of sampling and reduce the number of samples to be tested. Copyright © 2013 Elsevier B.V. All rights reserved.

  4. Differential regulation of glutamate receptors in trigeminal ganglia following masseter inflammation

    OpenAIRE

    Lee, Jongseok; Ro, Jin Y.

    2007-01-01

    The present study examined whether N-methyl-D-aspartate receptor (NMDAR) and 5-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) subunits and group I metabotropic glutamate receptors (mGluRs) are constitutively expressed in trigeminal ganglia (TG) using Western blot analysis in male Sprague Dawley rats. We then investigated whether experimental induction of masseter inflammation influences glutamate receptor expressions by comparing the protein levels from naïve rats to th...

  5. Uptake of Amino Acids and Their Metabolic Conversion into the Compatible Solute Proline Confers Osmoprotection to Bacillus subtilis

    Science.gov (United States)

    Zaprasis, Adrienne; Bleisteiner, Monika; Kerres, Anne; Hoffmann, Tamara

    2014-01-01

    The data presented here reveal a new facet of the physiological adjustment processes through which Bacillus subtilis can derive osmostress protection. We found that the import of proteogenic (Glu, Gln, Asp, Asn, and Arg) and of nonproteogenic (Orn and Cit) amino acids and their metabolic conversion into proline enhances growth under otherwise osmotically unfavorable conditions. Osmoprotection by amino acids depends on the functioning of the ProJ-ProA-ProH enzymes, but different entry points into this biosynthetic route are used by different amino acids to finally yield the compatible solute proline. Glu, Gln, Asp, and Asn are used to replenish the cellular pool of glutamate, the precursor for proline production, whereas Arg, Orn, and Cit are converted into γ-glutamic semialdehyde/Δ1-pyrroline-5-carboxylate, an intermediate in proline biosynthesis. The import of Glu, Gln, Asp, Asn, Arg, Orn, and Cit did not lead to a further increase in the size of the proline pool that is already present in osmotically stressed cells. Hence, our data suggest that osmoprotection of B. subtilis by this group of amino acids rests on the savings in biosynthetic building blocks and energy that would otherwise have to be devoted either to the synthesis of the proline precursor glutamate or of proline itself. Since glutamate is the direct biosynthetic precursor for proline, we studied its uptake and found that GltT, an Na+-coupled symporter, is the main uptake system for both glutamate and aspartate in B. subtilis. Collectively, our data show how effectively B. subtilis can exploit environmental resources to derive osmotic-stress protection through physiological means. PMID:25344233

  6. Green Tea Polyphenols Attenuated Glutamate Excitotoxicity via Antioxidative and Antiapoptotic Pathway in the Primary Cultured Cortical Neurons

    Directory of Open Access Journals (Sweden)

    Lin Cong

    2016-01-01

    Full Text Available Green tea polyphenols are a natural product which has antioxidative and antiapoptotic effects. It has been shown that glutamate excitotoxicity induced oxidative stress is linked to neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease. In this study we explored the neuroprotective effect of green teen polyphenols against glutamate excitotoxicity in the primary cultured cortical neurons. We found that green tea polyphenols protected against glutamate induced neurotoxicity in the cortical neurons as measured by MTT and TUNEL assays. Green tea polyphenols were then showed to inhibit the glutamate induced ROS release and SOD activity reduction in the neurons. Furthermore, our results demonstrated that green tea polyphenols restored the dysfunction of mitochondrial pro- or antiapoptotic proteins Bax, Bcl-2, and caspase-3 caused by glutamate. Interestingly, the neuroprotective effect of green tea polyphenols was abrogated when the neurons were incubated with siBcl-2. Taken together, these results demonstrated that green tea polyphenols protected against glutamate excitotoxicity through antioxidative and antiapoptotic pathways.

  7. Swimming pool cleaner poisoning

    Science.gov (United States)

    Swimming pool cleaner poisoning occurs when someone swallows this type of cleaner, touches it, or breathes in ... The harmful substances in swimming pool cleaner are: Bromine ... copper Chlorine Soda ash Sodium bicarbonate Various mild acids

  8. Utilization of glutamate/creatine ratios for proton spectroscopic diagnosis of meningiomas

    International Nuclear Information System (INIS)

    Hazany, Saman; Hesselink, John R.; Healy, John F.; Imbesi, Steven G.

    2007-01-01

    Our purpose was to determine the potential of metabolites other than alanine to diagnose intracranial meningiomas on proton magnetic resonance spectroscopy (MRS). Using a 1.5-T MR system the lesions were initially identified on FLAIR, and T1- and T2-weighted images. Employing standard point-resolved spectroscopy (PRESS) for single voxel proton MRS (TR 1500 ms, TE 30 ms, 128 acquisitions, voxel size 2 x 2 x 2 cm, acquisition time 3.12 min), MR spectra were obtained from 5 patients with meningiomas, from 20 with other intracranial lesions, and from 4 normal controls. Peak heights of nine resonances, including lipid, lactate, alanine, NAA (N-acetylaspartate), β/γ-Glx (glutamate + glutamine), creatine, choline, myo-inositol, and α-Glx/glutathione, were measured in all spectra. The relative quantity of each metabolite was measured as the ratio of its peak height to the peak height of creatine. Relative quantities of α-Glx/glutathione, β/γ-Glx, and total Glx/glutathione were significantly elevated in meningiomas compared to the 20 other intracranial lesions and the normal control brains. Alanine was found in four of five meningiomas, but lactate partially masked the alanine in three meningiomas. None of the other lesions or control brains showed an alanine peak. The one meningioma with no alanine and the three others with lactate had elevated Glx. While alanine is a relatively unique marker for meningioma, our results support the hypothesis that the combination of glutamate/creatine ratios and alanine on proton MRS is more specific and reliable for the diagnosis of meningiomas than alanine alone. (orig.)

  9. Utilization of glutamate/creatine ratios for proton spectroscopic diagnosis of meningiomas

    Energy Technology Data Exchange (ETDEWEB)

    Hazany, Saman [University of California, School of Medicine, San Diego, CA (United States); Hesselink, John R.; Healy, John F.; Imbesi, Steven G. [UCSD Medical Center, Department of Radiology, San Diego, CA (United States)

    2007-02-15

    Our purpose was to determine the potential of metabolites other than alanine to diagnose intracranial meningiomas on proton magnetic resonance spectroscopy (MRS). Using a 1.5-T MR system the lesions were initially identified on FLAIR, and T1- and T2-weighted images. Employing standard point-resolved spectroscopy (PRESS) for single voxel proton MRS (TR 1500 ms, TE 30 ms, 128 acquisitions, voxel size 2 x 2 x 2 cm, acquisition time 3.12 min), MR spectra were obtained from 5 patients with meningiomas, from 20 with other intracranial lesions, and from 4 normal controls. Peak heights of nine resonances, including lipid, lactate, alanine, NAA (N-acetylaspartate), {beta}/{gamma}-Glx (glutamate + glutamine), creatine, choline, myo-inositol, and {alpha}-Glx/glutathione, were measured in all spectra. The relative quantity of each metabolite was measured as the ratio of its peak height to the peak height of creatine. Relative quantities of {alpha}-Glx/glutathione, {beta}/{gamma}-Glx, and total Glx/glutathione were significantly elevated in meningiomas compared to the 20 other intracranial lesions and the normal control brains. Alanine was found in four of five meningiomas, but lactate partially masked the alanine in three meningiomas. None of the other lesions or control brains showed an alanine peak. The one meningioma with no alanine and the three others with lactate had elevated Glx. While alanine is a relatively unique marker for meningioma, our results support the hypothesis that the combination of glutamate/creatine ratios and alanine on proton MRS is more specific and reliable for the diagnosis of meningiomas than alanine alone. (orig.)

  10. Efficient pooling designs for library screening

    OpenAIRE

    Bruno, William J.; Knill, Emanuel; Balding, David J.; Bruce, D. C.; Doggett, N. A.; Sawhill, W. W.; Stallings, R. L.; Whittaker, Craig C.; Torney, David C.

    1994-01-01

    We describe efficient methods for screening clone libraries, based on pooling schemes which we call ``random $k$-sets designs''. In these designs, the pools in which any clone occurs are equally likely to be any possible selection of $k$ from the $v$ pools. The values of $k$ and $v$ can be chosen to optimize desirable properties. Random $k$-sets designs have substantial advantages over alternative pooling schemes: they are efficient, flexible, easy to specify, require fewer pools, and have er...

  11. Comparison of fecal pooling strategies for detection of Mycobacterium avium ssp. paratuberculosis in cattle.

    Science.gov (United States)

    McKenna, S L B; Ritter, C; Dohoo, I; Keefe, G P; Barkema, H W

    2018-05-23

    In herds with typical moderate to low within-herd prevalence, testing for Mycobacterium avium ssp. paratuberculosis (MAP), the infectious agent of Johne's disease, will be more cost-effective if individual fecal samples are cultured in composite pools. However, sensitivity to classify a pool containing 1 or more positive individual samples as positive may depend on pool size and number of individual positive samples within a pool. Fecal samples collected from 994 dairy cows sampled at slaughter were cultured to detect MAP. Culturing was done both individually and as composite pooled samples using the TREK ESP Culture System II broth medium (Thermo Fisher Scientific, Trek Diagnostic Systems Inc., Cleveland, OH). Composite samples consisted of pools containing feces from 3, 5, 8, 10, or 15 cows. The number of individual fecal culture-positive cows within each pool ranged from 0 to 4. Culture of individual fecal samples detected MAP in 36 (3.6%) of the 994 cows. Individual samples that were detected within the first 50 d by TREK ESP Culture System II were more likely to lead to a positive pool result. In total, 840 pooled fecal samples were examined for presence of MAP, and of those, 272 pools actually contained feces from fecal culture-positive cows. The crude sensitivity (proportion of pools that contained at least 1 fecal-positive cow that tested positive) for pools of 3, 5, 8, 10, and 15 was 47, 67, 44, 59, and 39%, respectively. Across pools, an increase of the number of fecal culture-positive samples from 1 to 2 enhanced overall crude sensitivity from 44 to 71%. However, sensitivity did not further increase for pools with 3 or 4 fecal culture-positive samples (63 and 60%, respectively). Additionally, a simulation analysis assessing probability of pooled fecal samples being positive in herds of 50 and 100 cows was conducted. The simulation assumed that 1, 2, or 5 cows per herd were MAP fecal culture-positive and that pools of 5 and 10 were used. This low

  12. A high dietary intake of sodium glutamate as flavoring (ajinomoto) causes gross changes in retinal morphology and function.

    Science.gov (United States)

    Ohguro, Hiroshi; Katsushima, Harumi; Maruyama, Ikuyo; Maeda, Tadao; Yanagihashi, Satsuki; Metoki, Tomomi; Nakazawa, Mitsuru

    2002-09-01

    The purpose of this study was to investigate the effects of glutamate accumulation in vitreous on retinal structure and function, due to a diet high in sodium glutamate. Three different diet groups were created, consisting of rats fed on a regular diet (diet A), a moderate excess of sodium glutamate diet (diet B) and a large excess of sodium glutamate diet (diet C). After 1, 3 and 6 months of the administration of these diets, amino acids concentrations in vitreous were analyzed. In addition, retinal morphology and function by electroretinogram (ERG) of three different diet groups were studied. Significant accumulation of glutamate in vitreous was observed in rats following addition of sodium glutamate to the diet as compared to levels with a regular diet. In the retinal morphology, thickness of retinal neuronal layers was remarkably thinner in rats fed on sodium glutamate diets than in those on a regular diet. TdT-dUTP terminal nick-end labelling (TUNEL) staining revealed significant accumulation of the positive staining cells within the retinal ganglion cell layers in retinas from diets B and C as compared with that from diet A. Similar to this, immunohistochemistry demonstrated increased expression of glial fibrillary acidic protein (GFAP) within the retinal inner layers from diets B and C as compared with diet A. Functionally, ERG responses were reduced in rats fed on a sodium glutamate diets as compared with those on a regular diet. The present study suggests that a diet with excess sodium glutamate over a period of several years may increase glutamate concentrations in vitreous and may cause retinal cell destruction.

  13. 21 CFR 1250.89 - Swimming pools.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Swimming pools. 1250.89 Section 1250.89 Food and... SANITATION Sanitation Facilities and Conditions on Vessels § 1250.89 Swimming pools. (a) Fill and draw swimming pools shall not be installed or used. (b) Swimming pools of the recirculation type shall be...

  14. Pharmacological or genetic orexin 1 receptor inhibition attenuates MK-801 induced glutamate release in mouse cortex

    Directory of Open Access Journals (Sweden)

    Leah eAluisio

    2014-05-01

    Full Text Available The orexin/hypocretin neuropeptides are produced by a cluster of neurons within the lateral posterior hypothalamus and participate in neuronal regulation by activating their receptors (OX1 and OX2 receptors. The orexin system projects widely through the brain and functions as an interface between multiple regulatory systems including wakefulness, energy balance, stress, reward and emotion. Recent studies have demonstrated that orexins and glutamate interact at the synaptic level and that orexins facilitate glutamate actions. We tested the hypothesis that orexins modulate glutamate signaling via OX1 receptors by monitoring levels of glutamate in frontal cortex of freely moving mice using enzyme coated biosensors under inhibited OX1 receptor conditions. MK-801, an NMDA receptor antagonist, was administered subcutaneously (0.178 mg/kg to indirectly disinhibit pyramidal neurons and therefore increase cortical glutamate release. In wild-type mice, pretreatment with the OX1 receptor antagonist GSK-1059865 (10 mg/kg S.C. which had no effect by itself, significantly attenuated the cortical glutamate release elicited by MK-801. OX1 receptor knockout mice had a blunted glutamate release response to MK-801 and exhibited about half of the glutamate release observed in wild-type mice in agreement with the data obtained with transient blockade of OX1 receptors. These results indicate that pharmacological (transient or genetic (permanent inhibition of the OX1 receptor similarly interfere with glutamatergic function in the cortex. Selectively targeting the OX1 receptor with an antagonist may normalize hyperglutamatergic states and thus may represent a novel therapeutic strategy for the treatment of various psychiatric disorders associated with hyperactive states.

  15. Α-amino-β-fluorocyclopropanecarboxylic acids as a new tool for drug development: synthesis of glutamic acid analogs and agonist activity towards metabotropic glutamate receptor 4.

    Science.gov (United States)

    Lemonnier, Gérald; Lion, Cédric; Quirion, Jean-Charles; Pin, Jean-Philippe; Goudet, Cyril; Jubault, Philippe

    2012-08-01

    Herein we describe the diastereoselective synthesis of glutamic acid analogs and the evaluation of their agonist activity towards metabotropic glutamate receptor subtype 4 (mGluR4). These analogs are based on a monofluorinated cyclopropane core substituted with an α-aminoacid function. The potential of this new building block as a tool for the development of a novel class of drugs is demonstrated with racemic analog 11a that displayed the best agonist activity with an EC50 of 340 nM. Copyright © 2012 Elsevier Ltd. All rights reserved.

  16. Lateral Preoptic Control of the Lateral Habenula through Convergent Glutamate and GABA Transmission

    Directory of Open Access Journals (Sweden)

    David J. Barker

    2017-11-01

    Full Text Available Summary: The lateral habenula (LHb is a brain structure that participates in cognitive and emotional processing and has been implicated in several mental disorders. Although one of the largest inputs to the LHb originates in the lateral preoptic area (LPO, little is known about how the LPO participates in the regulation of LHb function. Here, we provide evidence that the LPO exerts bivalent control over the LHb through the convergent transmission of LPO glutamate and γ-aminobutyric acid (GABA onto single LHb neurons. In vivo, both LPO-glutamatergic and LPO-GABAergic inputs to the LHb are activated by aversive stimuli, and their predictive cues yet produce opposing behaviors when stimulated independently. These results support a model wherein the balanced response of converging LPO-glutamate and LPO-GABA are necessary for a normal response to noxious stimuli, and an imbalance in LPO→LHb glutamate or GABA results in the type of aberrant processing that may underlie mental disorders. : Barker et al. show that distinct populations of lateral preoptic area glutamate and GABA neurons synapse together on single lateral habenula neurons and find that this “convergent neurotransmission” allows preoptic area neurons to exert bivalent control over single lateral habenula neurons and drive opposing motivational states. Keywords: preoptic, habenula, reward, aversion, synapse, glutamate, GABA, stress, calcium imaging, optogenetics, electron microscopy

  17. Clofibrate inhibits the umami-savory taste of glutamate.

    Science.gov (United States)

    Kochem, Matthew; Breslin, Paul A S

    2017-01-01

    In humans, umami taste can increase the palatability of foods rich in the amino acids glutamate and aspartate and the 5'-ribonucleotides IMP and GMP. Umami taste is transduced, in part, by T1R1-T1R3, a heteromeric G-protein coupled receptor. Umami perception is inhibited by sodium lactisole, which binds to the T1R3 subunit in vitro. Lactisole is structurally similar to the fibrate drugs. Clofibric acid, a lipid lowering drug, also binds the T1R3 subunit in vitro. The purpose of this study was to determine whether clofibric acid inhibits the umami taste of glutamate in human subjects. Ten participants rated the umami taste intensity elicited by 20 mM monosodium glutamate (MSG) mixed with varying concentrations of clofibric acid (0 to 16 mM). In addition, fourteen participants rated the effect of 1.4 mM clofibric acid on umami enhancement by 5' ribonucleotides. Participants were instructed to rate perceived intensity using a general Labeled Magnitude Scale (gLMS). Each participant was tested in triplicate. Clofibric acid inhibited umami taste intensity from 20 mM MSG in a dose dependent manner. Whereas MSG neat elicited "moderate" umami taste intensity, the addition of 16 mM clofibric acid elicited only "weak" umami intensity on average, and in some subjects no umami taste was elicited. We further show that 1.4 mM clofibric acid suppressed umami enhancement from GMP, but not from IMP. This study provides in vivo evidence that clofibric acid inhibits glutamate taste perception, presumably via T1R1-T1R3 inhibition, and lends further evidence that the T1R1-T1R3 receptor is the principal umami receptor in humans. T1R receptors are expressed extra-orally throughout the alimentary tract and in regulatory organs and are known to influence glucose and lipid metabolism. Whether clofibric acid as a lipid-lowering drug affects human metabolism, in part, through T1R inhibition warrants further examination.

  18. Utilizing the ultrasensitive Schistosoma up-converting phosphor lateral flow circulating anodic antigen (UCP-LF CAA) assay for sample pooling-strategies.

    Science.gov (United States)

    Corstjens, Paul L A M; Hoekstra, Pytsje T; de Dood, Claudia J; van Dam, Govert J

    2017-11-01

    Methodological applications of the high sensitivity genus-specific Schistosoma CAA strip test, allowing detection of single worm active infections (ultimate sensitivity), are discussed for efficient utilization in sample pooling strategies. Besides relevant cost reduction, pooling of samples rather than individual testing can provide valuable data for large scale mapping, surveillance, and monitoring. The laboratory-based CAA strip test utilizes luminescent quantitative up-converting phosphor (UCP) reporter particles and a rapid user-friendly lateral flow (LF) assay format. The test includes a sample preparation step that permits virtually unlimited sample concentration with urine, reaching ultimate sensitivity (single worm detection) at 100% specificity. This facilitates testing large urine pools from many individuals with minimal loss of sensitivity and specificity. The test determines the average CAA level of the individuals in the pool thus indicating overall worm burden and prevalence. When requiring test results at the individual level, smaller pools need to be analysed with the pool-size based on expected prevalence or when unknown, on the average CAA level of a larger group; CAA negative pools do not require individual test results and thus reduce the number of tests. Straightforward pooling strategies indicate that at sub-population level the CAA strip test is an efficient assay for general mapping, identification of hotspots, determination of stratified infection levels, and accurate monitoring of mass drug administrations (MDA). At the individual level, the number of tests can be reduced i.e. in low endemic settings as the pool size can be increased as opposed to prevalence decrease. At the sub-population level, average CAA concentrations determined in urine pools can be an appropriate measure indicating worm burden. Pooling strategies allowing this type of large scale testing are feasible with the various CAA strip test formats and do not affect

  19. Mitochondrial glutamate carriers from Drosophila melanogaster: biochemical, evolutionary and modeling studies.

    Science.gov (United States)

    Lunetti, Paola; Cappello, Anna Rita; Marsano, René Massimiliano; Pierri, Ciro Leonardo; Carrisi, Chiara; Martello, Emanuela; Caggese, Corrado; Dolce, Vincenza; Capobianco, Loredana

    2013-10-01

    The mitochondrial carriers are members of a family of transport proteins that mediate solute transport across the inner mitochondrial membrane. Two isoforms of the glutamate carriers, GC1 and GC2 (encoded by the SLC25A22 and SLC25A18 genes, respectively), have been identified in humans. Two independent mutations in SLC25A22 are associated with severe epileptic encephalopathy. In the present study we show that two genes (CG18347 and CG12201) phylogenetically related to the human GC encoding genes are present in the D. melanogaster genome. We have functionally characterized the proteins encoded by CG18347 and CG12201, designated as DmGC1p and DmGC2p respectively, by overexpression in Escherichia coli and reconstitution into liposomes. Their transport properties demonstrate that DmGC1p and DmGC2p both catalyze the transport of glutamate across the inner mitochondrial membrane. Computational approaches have been used in order to highlight residues of DmGC1p and DmGC2p involved in substrate binding. Furthermore, gene expression analysis during development and in various adult tissues reveals that CG18347 is ubiquitously expressed in all examined D. melanogaster tissues, while the expression of CG12201 is strongly testis-biased. Finally, we identified mitochondrial glutamate carrier orthologs in 49 eukaryotic species in order to attempt the reconstruction of the evolutionary history of the glutamate carrier function. Comparison of the exon/intron structure and other key features of the analyzed orthologs suggests that eukaryotic glutamate carrier genes descend from an intron-rich ancestral gene already present in the common ancestor of lineages that diverged as early as bilateria and radiata. © 2013.

  20. Evidence that glutamate mediates axon-to-Schwann cell signaling in the squid.

    Science.gov (United States)

    Lieberman, E M; Abbott, N J; Hassan, S

    1989-01-01

    High-frequency stimulation (100 Hz) of isolated giant axons of the small squid Alloteuthis subulata and the large squid Loligo forbesi caused the periaxonal Schwann cell resting potential (Em = -40 mV) to hyperpolarize up to 11 mV in direct proportion to train duration and action potential amplitude. In both species, the Schwann cell also hyperpolarized up to 17 mV with the application of L-glutamate (10(-9) to 10(-6) M), in a dose-dependent manner. By contrast, in the presence of 10(-8) M d-tubocurarine (d-TC) to block the cholinergic component of the Schwann cell response, Schwann cells depolarized 8-9 mV during electrical stimulation of the axon or application of L-glutamate. In the presence of 10(-5) M 2-amino-4-phosphonobutyrate (2-APB), the hyperpolarization to glutamate and to axon stimulation was blocked, whereas the cholinergic (carbachol-induced) hyperpolarization was unaffected. In experiments with Alloteuthis, L-aspartate (10(-7) M) also caused a Schwann cell hyperpolarization, but this was not blocked by 2-APB. In tests with glutamate receptor agonists and antagonists, quisqualate (10(-5) M) produced a hyperpolarization blocked by 10(-4) M L-glutamic acid diethylester (GDEE), which also blocked the response to axonal stimulation. Kainic acid (10(-4) M) also caused a hyperpolarization, but n-methyl-D-aspartate (NMDA; 10(-4) M), ibotenate (10(-5) M), alpha-amino-3-hydroxy-5-methyl-isoxazole proprionate (AMPA; (10(-4) M), and isethionate (10(-5) M) had no effect.(ABSTRACT TRUNCATED AT 250 WORDS)

  1. GABA and glutamate in schizophrenia: a 7 T ¹H-MRS study.

    Science.gov (United States)

    Marsman, Anouk; Mandl, René C W; Klomp, Dennis W J; Bohlken, Marc M; Boer, Vincent O; Andreychenko, Anna; Cahn, Wiepke; Kahn, René S; Luijten, Peter R; Hulshoff Pol, Hilleke E

    2014-01-01

    Schizophrenia is characterized by loss of brain volume, which may represent an ongoing pathophysiological process. This loss of brain volume may be explained by reduced neuropil rather than neuronal loss, suggesting abnormal synaptic plasticity and cortical microcircuitry. A possible mechanism is hypofunction of the NMDA-type of glutamate receptor, which reduces the excitation of inhibitory GABAergic interneurons, resulting in a disinhibition of glutamatergic pyramidal neurons. Disinhibition of pyramidal cells may result in excessive stimulation by glutamate, which in turn could cause neuronal damage or death through excitotoxicity. In this study, GABA/creatine ratios, and glutamate, NAA, creatine and choline concentrations in the prefrontal and parieto-occipital cortices were measured in 17 patients with schizophrenia and 23 healthy controls using proton magnetic resonance spectroscopy at an ultra-high magnetic field strength of 7 T. Significantly lower GABA/Cr ratios were found in patients with schizophrenia in the prefrontal cortex as compared to healthy controls, with GABA/Cr ratios inversely correlated with cognitive functioning in the patients. No significant change in the GABA/Cr ratio was found between patients and controls in the parieto-occipital cortex, nor were levels of glutamate, NAA, creatine, and choline differed in patients and controls in the prefrontal and parieto-occipital cortices. Our findings support a mechanism involving altered GABA levels distinguished from glutamate levels in the medial prefrontal cortex in schizophrenia, particularly in high functioning patients. A (compensatory) role for GABA through altered inhibitory neurotransmission in the prefrontal cortex may be ongoing in (higher functioning) patients with schizophrenia.

  2. Modal analysis of pool door in water tank

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Kang Soo; Jeong, Kyeong Hoon; Park, Chan Gook; Koo, In Soo [KAERI, Daejeon (Korea, Republic of)

    2012-10-15

    A pool door is installed at the chase of the pool gate by means of an overhead crane in the building of a research reactor. The principal function of the pool door, which is located between the reactor pool and service pool, is to separate the reactor pool from the service pool for the maintenance and/or the removal of the equipment either in the reactor pool or service pool. The pool door consists of stainless steel plates supported by structural steel frames and sealing components. The pool door is equipped with double inflatable gaskets. The configuration of the pool door is shown in Figure 1. The FEM analysis and theoretical calculation by the formula were performed to evaluate the natural frequency for the pool door in the water. The results from the two methods were compared.

  3. Increased glutamate/GABA+ ratio in a shared autistic and schizotypal trait phenotype termed Social Disorganisation.

    Science.gov (United States)

    Ford, Talitha C; Nibbs, Richard; Crewther, David P

    2017-01-01

    Autism and schizophrenia are multi-dimensional spectrum disorders that have substantial phenotypic overlap. This overlap is readily identified in the non-clinical population, and has been conceptualised as Social Disorganisation (SD). This study investigates the balance of excitatory glutamate and inhibitory γ -aminobutyric acid (GABA) concentrations in a non-clinical sample with high and low trait SD, as glutamate and GABA abnormalities are reported across the autism and schizophrenia spectrum disorders. Participants were 18 low (10 females) and 19 high (9 females) SD scorers aged 18 to 40 years who underwent 1 H-MRS for glutamate and GABA+macromolecule (GABA+) concentrations in right and left hemisphere superior temporal (ST) voxels. Reduced GABA+ concentration ( p  = 0.03) and increased glutamate/GABA+ ratio ( p  = 0.003) in the right ST voxel for the high SD group was found, and there was increased GABA+ concentration in the left compared to right ST voxel ( p  = 0.047). Bilateral glutamate concentration was increased for the high SD group ( p  = 0.006); there was no hemisphere by group interaction ( p  = 0.772). Results suggest that a higher expression of the SD phenotype may be associated with increased glutamate/GABA+ ratio in the right ST region, which may affect speech prosody processing, and lead behavioural characteristics that are shared within the autistic and schizotypal spectra.

  4. Mutations of the Corynebacterium glutamicum NCgl1221 Gene, Encoding a Mechanosensitive Channel Homolog, Induce l-Glutamic Acid Production▿

    OpenAIRE

    Nakamura, Jun; Hirano, Seiko; Ito, Hisao; Wachi, Masaaki

    2007-01-01

    Corynebacterium glutamicum is a biotin auxotroph that secretes l-glutamic acid in response to biotin limitation; this process is employed in industrial l-glutamic acid production. Fatty acid ester surfactants and penicillin also induce l-glutamic acid secretion, even in the presence of biotin. However, the mechanism of l-glutamic acid secretion remains unclear. It was recently reported that disruption of odhA, encoding a subunit of the 2-oxoglutarate dehydrogenase complex, resulted in l-gluta...

  5. Pu-erh Tea Protects the Nervous System by Inhibiting the Expression of Metabotropic Glutamate Receptor 5.

    Science.gov (United States)

    Li, Chunjie; Chai, Shaomeng; Ju, Yongzhi; Hou, Lu; Zhao, Hang; Ma, Wei; Li, Tian; Sheng, Jun; Shi, Wei

    2017-09-01

    Glutamate is one of the major excitatory neurotransmitters of the CNS and is essential for numerous key neuronal functions. However, excess glutamate causes massive neuronal death and brain damage owing to excitotoxicity via the glutamate receptors. Metabotropic glutamate receptor 5 (mGluR5) is one of the glutamate receptors and represents a promising target for studying neuroprotective agents of potential application in neurodegenerative diseases. Pu-erh tea, a fermented tea, mainly produced in Yunnan province, China, has beneficial effects, including the accommodation of the CNS. In this study, pu-erh tea markedly decreased the transcription and translation of mGluR5 compared to those by black and green teas. Pu-erh tea also inhibited the expression of Homer, one of the synaptic scaffolding proteins binding to mGluR5. Pu-erh tea protected neural cells from necrosis via blocked Ca 2+ influx and inhibited protein kinase C (PKC) activation induced by excess glutamate. Pu-erh tea relieved rat epilepsy induced by LiCl-pilocarpine in behavioural and physiological assays. Pu-erh tea also decreased the expression of mGluR5 in the hippocampus. These results show that the inhibition of mGluR5 plays a role in protecting neural cells from glutamate. The results also indicate that pu-erh tea contains biological compounds binding transcription factors and inhibiting the expression of mGluR5 and identify pu-erh tea as a novel natural neuroprotective agent.

  6. Internalization and cellular pools of never growth factor in pheochromocytoma (PC12) cells

    International Nuclear Information System (INIS)

    Neet, K.E.; Kasaian, M.

    1987-01-01

    Nerve Growth Factor (NGF) binds to a cell surface receptor on responsive neuronal cells to initiate cell maintenance and/or differentiation regimes. The purpose of these studies was to define quantitatively the fate of NGF in PC12 cells with respect to various cellular compartments in a single series of biochemical experiments. Different binding methodologies were evaluated in suspension and on plates. 50 pM 125 I-NGF was bound to rat PC12 cells in suspension for 30 min at 37 0 , followed by various methods and combinations of methods to remove subsets of bound ligand. Distinction could be made between NGF bound to fast vs. slow cell surface receptors, NGF bound to slow receptors at the cell surface vs. cell interior, and detergent-soluble vs. cytoskeletally-attached NGF. These treatments defined the relative size of five pools, including the fast receptor (65%), two intracellular compartments (12% and 3%) susceptible to nonionic detergent, and a detergent-stable intracellular pool of ligand (16%). At 37 0 the cold chase stable and the acid stable pools were about the same size because of rapid internalization, but the slow receptor was measurable at 4 0 . Inhibitors were used to define the route of NGF through the cell from the plasma membrane to degradation. Chloroquine caused accumulation of NGF only in pools that were not associated with the cytoskeleton, implicating this compartment in supplying ligand to the lysosome. Results with cytochalasin B and colchicine and suggested both microfilament and microtubule pathways in NGF degradation. A model for the movement of NGF through the cell was developed based on these observations

  7. Conformational analysis of glutamic acid: a density functional approach using implicit continuum solvent model.

    Science.gov (United States)

    Turan, Başak; Selçuki, Cenk

    2014-09-01

    Amino acids are constituents of proteins and enzymes which take part almost in all metabolic reactions. Glutamic acid, with an ability to form a negatively charged side chain, plays a major role in intra and intermolecular interactions of proteins, peptides, and enzymes. An exhaustive conformational analysis has been performed for all eight possible forms at B3LYP/cc-pVTZ level. All possible neutral, zwitterionic, protonated, and deprotonated forms of glutamic acid structures have been investigated in solution by using polarizable continuum model mimicking water as the solvent. Nine families based on the dihedral angles have been classified for eight glutamic acid forms. The electrostatic effects included in the solvent model usually stabilize the charged forms more. However, the stability of the zwitterionic form has been underestimated due to the lack of hydrogen bonding between the solute and solvent; therefore, it is observed that compact neutral glutamic acid structures are more stable in solution than they are in vacuum. Our calculations have shown that among all eight possible forms, some are not stable in solution and are immediately converted to other more stable forms. Comparison of isoelectronic glutamic acid forms indicated that one of the structures among possible zwitterionic and anionic forms may dominate over the other possible forms. Additional investigations using explicit solvent models are necessary to determine the stability of charged forms of glutamic acid in solution as our results clearly indicate that hydrogen bonding and its type have a major role in the structure and energy of conformers.

  8. Glutamate in schizophrenia: clinical and research implications.

    Science.gov (United States)

    Goff, D C; Wine, L

    1997-10-30

    The excitatory amino acids, glutamate and aspartate, are of interest to schizophrenia research because of their roles in neurodevelopment, neurotoxicity and neurotransmission. Recent evidence suggests that densities of glutamatergic receptors and the ratios of subunits composing these receptors may be altered in schizophrenia, although it is unclear whether these changes are primary or compensatory. Agents acting at the phencyclidine binding site of the NMDA receptor produce symptoms of schizophrenia in normal subjects, and precipitate relapse in patients with schizophrenia. The improvement of negative symptoms with agents acting at the glycine modulatory site of the NMDA receptor, as well as preliminary evidence that clozapine may differ from conventional neuroleptic agents in its effects on glutamatergic systems, suggest that clinical implications may follow from this model. While geriatric patients may be at increased risk for glutamate-mediated neurotoxicity, very little is known about the specific relevance of this model to geriatric patients with schizophrenia.

  9. Elevated systemic glutamic acid level in the non-obese diabetic mouse is Idd linked and induces beta cell apoptosis.

    Science.gov (United States)

    Banday, Viqar Showkat; Lejon, Kristina

    2017-02-01

    Although type 1 diabetes (T1D) is a T-cell-mediated disease in the effector stage, the mechanism behind the initial beta cell assault is less understood. Metabolomic differences, including elevated levels of glutamic acid, have been observed in patients with T1D before disease onset, as well as in pre-diabetic non-obese diabetic (NOD) mice. Increased levels of glutamic acid damage both neurons and beta cells, implying that this could contribute to the initial events of T1D pathogenesis. We investigated the underlying genetic factors and consequences of the increased levels of glutamic acid in NOD mice. Serum glutamic acid levels from a (NOD×B6)F 2 cohort (n = 182) were measured. By genome-wide and Idd region targeted microsatellite mapping, genetic association was detected for six regions including Idd2, Idd4 and Idd22. In silico analysis of potential enzymes and transporters located in and around the mapped regions that are involved in glutamic acid metabolism consisted of alanine aminotransferase, glutamic-oxaloacetic transaminase, aldehyde dehydrogenase 18 family, alutamyl-prolyl-tRNA synthetase, glutamic acid transporters GLAST and EAAC1. Increased EAAC1 protein expression was observed in lysates from livers of NOD mice compared with B6 mice. Functional consequence of the elevated glutamic acid level in NOD mice was tested by culturing NOD. Rag2 -/- Langerhans' islets with glutamic acid. Induction of apoptosis of the islets was detected upon glutamic acid challenge using TUNEL assay. Our results support the notion that a dysregulated metabolome could contribute to the initiation of T1D. We suggest that targeting of the increased glutamic acid in pre-diabetic patients could be used as a potential therapy. © 2016 John Wiley & Sons Ltd.

  10. Numerical modeling of sodium fire – Part II: Pool combustion and combined spray and pool combustion

    International Nuclear Information System (INIS)

    Sathiah, Pratap; Roelofs, Ferry

    2014-01-01

    Highlights: • A CFD based method is proposed for the simulation of sodium pool combustion. • A sodium evaporation based model is proposed to model sodium pool evaporation. • The proposed method is validated against sodium pool experiments of Newman and Payne. • The results obtained using the proposed method are in good agreement with the experiments. - Abstract: The risk of sodium-air reaction has received considerable attention after the sodium-fire accident in Monju reactor. The fires resulting from the sodium-air reaction can be detrimental to the safety of a sodium fast reactor. Therefore, predicting the consequences of a sodium fire is important from a safety point of view. A computational method based on CFD is proposed here to simulate sodium pool fire and understand its characteristics. The method solves the Favre-averaged Navier-Stokes equation and uses a non-premixed mixture fraction based combustion model. The mass transfer of sodium vapor from the pool surface to the flame is obtained using a sodium evaporation model. The proposed method is then validated against well-known sodium pool experiments of Newman and Payne. The flame temperature and location predicted by the model are in good agreement with experiments. Furthermore, the trends of the mean burning rate with initial pool temperature and oxygen concentration are captured well. Additionally, parametric studies have been performed to understand the effects of pool diameter and initial air temperature on the mean burning rate. Furthermore, the sodium spray and sodium pool combustion models are combined to simulate simultaneous spray and pool combustion. Simulations were performed to demonstrate that the combined code could be applied to simulate this. Once sufficiently validated, the present code can be used for safety evaluation of a sodium fast reactor

  11. Numerical modeling of sodium fire – Part II: Pool combustion and combined spray and pool combustion

    Energy Technology Data Exchange (ETDEWEB)

    Sathiah, Pratap, E-mail: pratap.sathiah78@gmail.com [Shell Global Solutions Ltd., Brabazon House, Concord Business Park, Threapwood Road, Manchester M220RR (United Kingdom); Roelofs, Ferry, E-mail: roelofs@nrg.eu [Nuclear Research and Consultancy Group (NRG), Westerduinweg 3, 1755ZG Petten (Netherlands)

    2014-10-15

    Highlights: • A CFD based method is proposed for the simulation of sodium pool combustion. • A sodium evaporation based model is proposed to model sodium pool evaporation. • The proposed method is validated against sodium pool experiments of Newman and Payne. • The results obtained using the proposed method are in good agreement with the experiments. - Abstract: The risk of sodium-air reaction has received considerable attention after the sodium-fire accident in Monju reactor. The fires resulting from the sodium-air reaction can be detrimental to the safety of a sodium fast reactor. Therefore, predicting the consequences of a sodium fire is important from a safety point of view. A computational method based on CFD is proposed here to simulate sodium pool fire and understand its characteristics. The method solves the Favre-averaged Navier-Stokes equation and uses a non-premixed mixture fraction based combustion model. The mass transfer of sodium vapor from the pool surface to the flame is obtained using a sodium evaporation model. The proposed method is then validated against well-known sodium pool experiments of Newman and Payne. The flame temperature and location predicted by the model are in good agreement with experiments. Furthermore, the trends of the mean burning rate with initial pool temperature and oxygen concentration are captured well. Additionally, parametric studies have been performed to understand the effects of pool diameter and initial air temperature on the mean burning rate. Furthermore, the sodium spray and sodium pool combustion models are combined to simulate simultaneous spray and pool combustion. Simulations were performed to demonstrate that the combined code could be applied to simulate this. Once sufficiently validated, the present code can be used for safety evaluation of a sodium fast reactor.

  12. 10 CFR 36.63 - Pool water purity.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 1 2010-01-01 2010-01-01 false Pool water purity. 36.63 Section 36.63 Energy NUCLEAR... § 36.63 Pool water purity. (a) Pool water purification system must be run sufficiently to maintain the conductivity of the pool water below 20 microsiemens per centimeter under normal circumstances. If pool water...

  13. Aberrant modulation of a delayed rectifier potassium channel by glutamate in Alzheimer's disease.

    Science.gov (United States)

    Poulopoulou, Cornelia; Markakis, Ioannis; Davaki, Panagiota; Tsaltas, Eleftheria; Rombos, Antonis; Hatzimanolis, Alexandros; Vassilopoulos, Dimitrios

    2010-02-01

    In Alzheimer's disease (AD), potassium channel abnormalities have been reported in both neural and peripheral tissues. Herein, using whole-cell patch-clamp, we demonstrate an aberrant glutamate-dependent modulation of K(V)1.3 channels in T lymphocytes of AD patients. Although intrinsic K(V)1.3 properties in patients were similar to healthy individuals, glutamate (1-1000 microM) failed to yield the hyperpolarizing shift normally observed in K(V)1.3 steady-state inactivation (-4.4+/-2.7 mV in AD vs. -14.3+/-2.5 mV in controls, 10 microM glutamate), resulting in a 4-fold increase of resting channel activity. Specific agonist and antagonist data indicate that this abnormality is due to dysfunction of cognate group II mGluRs. Given that glutamate is present in plasma and that both mGluRs and K(V)1.3 channels regulate T-lymphocyte responsiveness, our finding may account for the presence of immune-associated alterations in AD. Furthermore, if this aberration reflects a corresponding one in neural tissue, it could provide a potential target in AD pathogenesis.

  14. Glutamate system, amyloid β peptides and tau protein: functional interrelationships and relevance to Alzheimer disease pathology

    Science.gov (United States)

    Revett, Timothy J.; Baker, Glen B.; Jhamandas, Jack; Kar, Satyabrata

    2013-01-01

    Alzheimer disease is the most prevalent form of dementia globally and is characterized premortem by a gradual memory loss and deterioration of higher cognitive functions and postmortem by neuritic plaques containing amyloid β peptide and neurofibrillary tangles containing phospho-tau protein. Glutamate is the most abundant neurotransmitter in the brain and is essential to memory formation through processes such as long-term potentiation and so might be pivotal to Alzheimer disease progression. This review discusses how the glutamatergic system is impaired in Alzheimer disease and how interactions of amyloid β and glutamate influence synaptic function, tau phosphorylation and neurodegeneration. Interestingly, glutamate not only influences amyloid β production, but also amyloid β can alter the levels of glutamate at the synapse, indicating that small changes in the concentrations of both molecules could influence Alzheimer disease progression. Finally, we describe how the glutamate receptor antagonist, memantine, has been used in the treatment of individuals with Alzheimer disease and discuss its effectiveness. PMID:22894822

  15. Experimental study of aerosol reentrainment from flashing pool in ALPHA program

    International Nuclear Information System (INIS)

    Kudo, T.; Yamano, N.; Moriyama, K.; Maruyama, Y.; Sugimoto, J.

    1994-01-01

    Aerosol reentrainment experiments are being performed as a part of the ALPHA (Assessment of Loads and Performance of Containment in a Hypothetical Accident) program at JAERI (Japan Atomic Energy Research Institute). The major objective of the experiments is to quantify and characterize the reentrainment of the dissolved material from a flashing pool during the rapid depressurization of a reactor containment vessel. Two experiments were performed. In the experiments a water pool dissolving sodium sulfate as FP simulant was located in the model containment vessel and the containment breach area was simulated with an orifice with 24 mm diameter. This orifice was estimated to give the same order of depressurization rate as the case of BWR Mark 1 containment failure with most likely breach size. In the first experiment ARE001, a pool water of 800 kg dissolving 50 kg of sodium sulfate was employed. The model containment was depressurized from 1.5 MPa to 0.1 MPa in approximately 45 minutes. In the second experiment ARE002, the mass of the pool water was reduced to 400 kg dissolving 25 kg of sodium sulfate. The internal pressure of the containment was decreased from 1.3 MPa to 0.1 MPa in approximately 40 minutes. At the beginning of the depressurization the pool water was heated to the saturation temperature at the internal pressure of the containment. The entrained droplets were sampled during depressurization period. Sodium sulfate deposited in all parts of the test facility was collected and weighed after the experiments. Results of the experiments showed that very small fraction of the dissolved material (less than 0.03%) was reentrained although approximately, 20% of water was evaporated from the pool water. The reentrained mass predicted with the Kataoka-Ishii model was approximately 1/110 of the mass evaluated in the experiments. This may be due to multi-dimensional features of the pool geometry. (author)

  16. Model of large pool fires

    Energy Technology Data Exchange (ETDEWEB)

    Fay, J.A. [Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States)]. E-mail: jfay@mit.edu

    2006-08-21

    A two zone entrainment model of pool fires is proposed to depict the fluid flow and flame properties of the fire. Consisting of combustion and plume zones, it provides a consistent scheme for developing non-dimensional scaling parameters for correlating and extrapolating pool fire visible flame length, flame tilt, surface emissive power, and fuel evaporation rate. The model is extended to include grey gas thermal radiation from soot particles in the flame zone, accounting for emission and absorption in both optically thin and thick regions. A model of convective heat transfer from the combustion zone to the liquid fuel pool, and from a water substrate to cryogenic fuel pools spreading on water, provides evaporation rates for both adiabatic and non-adiabatic fires. The model is tested against field measurements of large scale pool fires, principally of LNG, and is generally in agreement with experimental values of all variables.

  17. Model of large pool fires

    International Nuclear Information System (INIS)

    Fay, J.A.

    2006-01-01

    A two zone entrainment model of pool fires is proposed to depict the fluid flow and flame properties of the fire. Consisting of combustion and plume zones, it provides a consistent scheme for developing non-dimensional scaling parameters for correlating and extrapolating pool fire visible flame length, flame tilt, surface emissive power, and fuel evaporation rate. The model is extended to include grey gas thermal radiation from soot particles in the flame zone, accounting for emission and absorption in both optically thin and thick regions. A model of convective heat transfer from the combustion zone to the liquid fuel pool, and from a water substrate to cryogenic fuel pools spreading on water, provides evaporation rates for both adiabatic and non-adiabatic fires. The model is tested against field measurements of large scale pool fires, principally of LNG, and is generally in agreement with experimental values of all variables

  18. Glutamate/GABA+ ratio is associated with the psychosocial domain of autistic and schizotypal traits.

    Science.gov (United States)

    Ford, Talitha C; Nibbs, Richard; Crewther, David P

    2017-01-01

    The autism and schizophrenia spectra overlap to a large degree in the social and interpersonal domains. Similarly, abnormal excitatory glutamate and inhibitory γ-aminobutyric acid (GABA) neurotransmitter concentrations have been reported for both spectra, with the interplay of these neurotransmitters important for cortical excitation to inhibition regulation. This study investigates whether these neurotransmitter abnormalities are specific to the shared symptomatology, and whether the degree of abnormality increases with increasing symptom severity. Hence, the relationship between the glutamate/GABA ratio and autism and schizophrenia spectrum traits in an unmedicated, subclinical population was investigated. A total of 37 adults (19 female, 18 male) aged 18-38 years completed the Autism Spectrum Quotient (AQ) and Schizotypal Personality Questionnaire (SPQ), and participated in the resting state proton magnetic resonance spectroscopy study in which sequences specific for quantification of glutamate and GABA+ concentration were applied to a right and left superior temporal voxel. There were significant, moderate, positive relationships between right superior temporal glutamate/GABA+ ratio and AQ, SPQ and AQ+SPQ total scores (pGABA+ coinciding with higher scores on these subscales. Only the relationships between glutamate/GABA+ ratio and Social Anxiety, Constricted Affect, Social Skills and Communication survived multiple comparison correction (pGABA+ ratio reduced with increasing restricted imagination (pschizophrenia spectra.

  19. Atlantic Warm Pool Trigger for the Younger Dryas Climate Event

    Science.gov (United States)

    Abdul, N. A.; Mortlock, R. A.; Wright, J. D.; Fairbanks, R. G.; Teneva, L. T.

    2011-12-01

    There is growing evidence that variability in the size and heat content of the tropical Atlantic Warm Pool impacts circum-North Atlantic climate via the Atlantic Multi-decadal Oscillation mode (Wang et al., 2008). The Atlantic Warm Pool spans the Gulf of Mexico, Caribbean Sea and the western tropical North Atlantic. Barbados is located near the center of the tropical Atlantic Warm Pool and coupled ocean models suggest that Barbados remains near the center of the tropical Atlantic Warm Pool under varying wind stress simulations. Measurements of the oxygen isotope paleothermometer in Acropora palmata coral species recovered from cores offshore Barbados, show a 3oC monotonic decrease in sea surface temperature from 13106 ± 83 to 12744 ± 61 years before present (errors given as 2 sigma). This interval corresponds to a sea level rise from 71.4 meters to 67.1 meters below present levels at Barbados. The 3oC temperature decrease is captured in eight A. palmata specimens that are in stratigraphic sequence, 230Th/234U dated, and analyzed for oxygen isotopes. All measurements are replicated. We are confident that this is the warm pool equivalent of the Younger Dryas climate event. The initiation of this temperature drop in the Atlantic Warm Pool predates the Younger Dryas start in Greenland ice cores, reported to start at 12896 ± 138 years (relative to AD 2000) (Rasmussen et al., 2006), while few other Younger Dryas climate records are dated with similar accuracy to make the comparison. Rasmussen, S.O., Andersen, K.K., Svensson, A.M., Steffensen, J.P., Vinther, B.M., Clausen, H.B., Siggaard-Andersen, M.L., Johnsen, S.J., Larsen, L.B., Dahl-Jensen, D., Bigler, M., Röthlisberger, R., Fischer, H., Goto-Azuma, K., Hansson, M.E., and Ruth, U., 2006, A new Greenland ice core chronology for the last glacial termination: J. Geophys. Res., v. 111, p. D06102. Wang, C., Lee, S.-K., and Enfield, D.B., 2008, Atlantic Warm Pool acting as a link between Atlantic Multidecadal

  20. Imaging of the human heart after administration of l-(N-13)glutamate

    International Nuclear Information System (INIS)

    Gelbard, A.S.; Benua, R.S.; Reiman, R.E.; McDonald, J.M.; Vomero, J.J.; Laughlin, J.S.

    1980-01-01

    In normal volunteers and cancer patients, studies using L-(N-13)glutamate as an imaging agent showed localization of N-13 activity in the heart. Other organs that were well visualized include the liver, pancreas, and salivary glands. The concentration of N-13 activity in the human heart could not be predicted from previous studies involving myocardial uptake in dogs and rodents after administration of L-(N-13)glutamate

  1. Direct visualization of glutamate transporter elevator mechanism by high-speed AFM.

    Science.gov (United States)

    Ruan, Yi; Miyagi, Atsushi; Wang, Xiaoyu; Chami, Mohamed; Boudker, Olga; Scheuring, Simon

    2017-02-14

    Glutamate transporters are essential for recovery of the neurotransmitter glutamate from the synaptic cleft. Crystal structures in the outward- and inward-facing conformations of a glutamate transporter homolog from archaebacterium Pyrococcus horikoshii , sodium/aspartate symporter Glt Ph , suggested the molecular basis of the transporter cycle. However, dynamic studies of the transport mechanism have been sparse and indirect. Here we present high-speed atomic force microscopy (HS-AFM) observations of membrane-reconstituted Glt Ph at work. HS-AFM movies provide unprecedented real-space and real-time visualization of the transport dynamics. Our results show transport mediated by large amplitude 1.85-nm "elevator" movements of the transport domains consistent with previous crystallographic and spectroscopic studies. Elevator dynamics occur in the absence and presence of sodium ions and aspartate, but stall in sodium alone, providing a direct visualization of the ion and substrate symport mechanism. We show unambiguously that individual protomers within the trimeric transporter function fully independently.

  2. Theoretical and experimental studies of thermal stratification in hot and cold pools of PFBR

    International Nuclear Information System (INIS)

    Velusamy, K.; Titus, G.; Rajakumar, A.; Ravichandran, G.; Padmakumar, G.; Vaidyanathan, G.; Kale, R.D.; Chetal, S.C.; Bhoje, S.B.

    1994-01-01

    Results of experimental studies carried out in two water models of size 1/24 and 1/15, to assess the free level fluctuation in the hot pool of PFBR are presented. The results when extrapolated to the prototype gives a ripple height of 50 mm. The results of thermal stratification studies carried out in 1/24 scale model, using hot and cold water indicates that the interface velocity can be correlated with the Richardson number. The paper also gives the details of computer codes developed for the estimation of flow and temperature fields in the pools. (author)

  3. Altered medial temporal activation related to local glutamate levels in subjects with prodromal signs of psychosis.

    Science.gov (United States)

    Valli, Isabel; Stone, James; Mechelli, Andrea; Bhattacharyya, Sagnik; Raffin, Marie; Allen, Paul; Fusar-Poli, Paolo; Lythgoe, David; O'Gorman, Ruth; Seal, Marc; McGuire, Philip

    2011-01-01

    Both medial temporal cortical dysfunction and perturbed glutamatergic neurotransmission are regarded as fundamental pathophysiological features of psychosis. However, although animal models of psychosis suggest that these two abnormalities are interrelated, their relationship in humans has yet to be investigated. We used a combination of functional magnetic resonance imaging and magnetic resonance spectroscopy to investigate the relationship between medial temporal activation during an episodic memory task and local glutamate levels in 22 individuals with an at-risk mental state for psychosis and 14 healthy volunteers. We observed a significant between-group difference in the coupling of medial temporal activation with local glutamate levels. In control subjects, medial temporal activation during episodic encoding was positively associated with medial temporal glutamate. However, in the clinical population, medial temporal activation was reduced, and the relationship with glutamate was absent. In individuals at high risk of psychosis, medial temporal dysfunction seemed related to a loss of the normal relationship with local glutamate levels. This study provides the first evidence that links medial temporal dysfunction with the central glutamate system in humans and is consistent with evidence that drugs that modulate glutamatergic transmission might be useful in the treatment of psychosis. Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  4. Bacterial cytolysin during meningitis disrupts the regulation of glutamate in the brain, leading to synaptic damage.

    Directory of Open Access Journals (Sweden)

    Carolin Wippel

    Full Text Available Streptococcus pneumoniae (pneumococcal meningitis is a common bacterial infection of the brain. The cholesterol-dependent cytolysin pneumolysin represents a key factor, determining the neuropathogenic potential of the pneumococci. Here, we demonstrate selective synaptic loss within the superficial layers of the frontal neocortex of post-mortem brain samples from individuals with pneumococcal meningitis. A similar effect was observed in mice with pneumococcal meningitis only when the bacteria expressed the pore-forming cholesterol-dependent cytolysin pneumolysin. Exposure of acute mouse brain slices to only pore-competent pneumolysin at disease-relevant, non-lytic concentrations caused permanent dendritic swelling, dendritic spine elimination and synaptic loss. The NMDA glutamate receptor antagonists MK801 and D-AP5 reduced this pathology. Pneumolysin increased glutamate levels within the mouse brain slices. In mouse astrocytes, pneumolysin initiated the release of glutamate in a calcium-dependent manner. We propose that pneumolysin plays a significant synapto- and dendritotoxic role in pneumococcal meningitis by initiating glutamate release from astrocytes, leading to subsequent glutamate-dependent synaptic damage. We outline for the first time the occurrence of synaptic pathology in pneumococcal meningitis and demonstrate that a bacterial cytolysin can dysregulate the control of glutamate in the brain, inducing excitotoxic damage.

  5. Mercury concentrations and pools in four Sierra Nevada forest sites, and relationships to organic carbon and nitrogen

    Directory of Open Access Journals (Sweden)

    D. Obrist

    2009-05-01

    Full Text Available This study presents data on mercury (Hg concentrations, stochiometric relations to carbon (C and nitrogen (N, and Hg pool sizes in four Sierra Nevada forest sites of similar exposure and precipitation regimes, and hence similar atmospheric deposition, to evaluate how ecosystem parameters control Hg retention in ecosystems. In all four sites, the largest amounts of Hg reside in soils which account for 94–98% of ecosystem pools. Hg concentrations and Hg/C ratios increase in the following order: Green Needles/Leavesr2=0.58 and N and C (r2=0.64 in decomposing litter, but a positive correlation between litter Hg and N (r2=0.70. These inverse relations may reflect preferential retention of N and Hg over C during decomposition, or may be due to older age of decomposed litter layers which are exposed to longer-term atmospheric Hg deposition in the field. The results indicate that litter Hg levels depend on decomposition stage and may not follow generally observed positive relationships between Hg and organic C.

    Mineral soil layers show strong positive correlations of Hg to C across all sites and soil horizons (r2=0.83, but Hg concentrations are even more closely related to N with a similar slope to that observed in litter (r2=0.92. Soil N levels alone explain over 90% of Hg pool sizes across the four Sierra Nevada forest sites. This suggests that soil organic N and C groups provide sorption sites for Hg to retain atmospheric deposition. However, the patterns could be due to indirect relationships where high soil N and C levels reflect high ecosystem productivity which leads to corresponding high atmospheric Hg deposition inputs via leaf litterfall and plant senescence. Our results also show that two of the sites previously affected by

  6. 4,4-Dimethyl- and diastereomeric 4-hydroxy-4-methyl-(2S)-glutamate analogues display distinct pharmacological profiles at ionotropic glutamate receptors and excitatory amino acid transporters

    DEFF Research Database (Denmark)

    Bunch, Lennart; Pickering, Darryl S; Gefflaut, Thierry

    2009-01-01

    this approach has provided important insight into the structure-activity relationships (SAR) for ionotropic and metabotropic glutamate receptors (iGluRs and mGluRs), as well as the excitatory amino acid transporters (EAATs). In this work, three 4,4-disubstituted Glu analogues 1-3, which are hybrid structures......Subtype-selective ligands are of great interest to the scientific community, as they provide a tool for investigating the function of one receptor or transporter subtype when functioning in its native environment. Several 4-substituted (S)-glutamate (Glu) analogues were synthesized, and altogether...

  7. Synthesis and in vitro pharmacology at AMPA and kainate preferring glutamate receptors of 4-heteroarylmethylidene glutamate analogues

    DEFF Research Database (Denmark)

    Valgeirsson, Jon; Christensen, Jeppe K; Kristensen, Anders S

    2003-01-01

    affinity for the GluR2 subtype of AMPA receptors. As an attempt to develop new pharmacological tools for studies of GluR5 receptors, (S)-E-4-(2-thiazolylmethylene)glutamic acid (4a) was designed as a structural hybrid between 1 and 3. 4a was shown to be a potent GluR5 agonist and a high affinity ligand...

  8. Utilization of barley or wheat bran to bioconvert glutamate to γ-aminobutyric acid (GABA).

    Science.gov (United States)

    Jin, Wen-Jie; Kim, Min-Ju; Kim, Keun-Sung

    2013-09-01

    This study deals with the utilization of agro-industrial wastes created by barley and wheat bran in the production of a value-added product, γ-aminobutyric acid (GABA). The simple and eco-friendly reaction requires no pretreatment or microbial fermentation steps but uses barley or wheat bran as an enzyme source, glutamate as a substrate, and pyridoxal 5'-phosphate (PLP) as a cofactor. The optimal reaction conditions were determined on the basis of the temperatures and times used for the decarboxylation reactions and the initial concentrations of barley or wheat bran, glutamate, and PLP. The optimal reactions produced 9.2 mM of GABA from 10 mM glutamate, yielding a 92% GABA conversion rate, when barley bran was used and 6.0 mM of GABA from 10 mM glutamate, yielding a 60% GABA conversion rate, when wheat bran was used. The results imply that barley bran is more efficient than wheat bran in the production of GABA. © 2013 Institute of Food Technologists®

  9. Histochemical Studies of the Effects of Monosodium Glutamate on ...

    African Journals Online (AJOL)

    Uche

    Key words: Monosodium glutamate; histochemical effect; liver enzymes; hepatocytes; atrophic and degenerative changes;. Wistar rats. ... disease, Huntington‟s disease, and amyotrophic ... ascending grade of alcohol (ethanol), cleared in.

  10. Experimental study on size effect of siphon-breaking hole in the real-scaled reactor pool

    International Nuclear Information System (INIS)

    Kang, Soon Ho; Ahn, Ho Seon; Kim, Ji Min; Kim, Moo Hwan; Lee, Kwon Yeong; Seo, Kyoung Woo; Chi, Dae Young

    2012-01-01

    A rupture in the primary piping of a cooling system with a heat source or in a research reactor could lead to a loss-of-coolant accident (LOCA). However, if the water level of the reactor pool could be sustained and a reactor scram follows, the heat source could be cooled by natural convection, and significant accidents could be avoided. When a piping-system rupture accident occurs, the coolant starts to siphon out of the reactor pool until the pressure head between the inlet and outlet is removed or the siphon flow is interrupted. Therefore, a siphon-breaker mechanism can be adopted as a passive safety device to maintain the reactor water level. The gas entrainment is used to block the continuous loss of coolant by interrupting the siphon flow. Siphon breaking is complicated due to the transient, turbulent, two-phase flow mode, so suitable models or correlations that describe this phenomenon do not exist, and no general analysis been developed. Previous researchers have conducted experiments and numerical simulations to design a siphon breaker to meet their needs. Previous research on siphon breaking has not been conducted systemically, and no literature exists, even though the topic is greatly concerned with hydraulic safety. In this study, siphon-breaking holes were used as siphon breakers, and their performance was evaluated by the residual water quantity. Flow visualization was conducted to interpret the siphon-breaking phenomenon

  11. TAAR1 Modulates Cortical Glutamate NMDA Receptor Function

    Science.gov (United States)

    Espinoza, Stefano; Lignani, Gabriele; Caffino, Lucia; Maggi, Silvia; Sukhanov, Ilya; Leo, Damiana; Mus, Liudmila; Emanuele, Marco; Ronzitti, Giuseppe; Harmeier, Anja; Medrihan, Lucian; Sotnikova, Tatyana D; Chieregatti, Evelina; Hoener, Marius C; Benfenati, Fabio; Tucci, Valter; Fumagalli, Fabio; Gainetdinov, Raul R

    2015-01-01

    Trace Amine-Associated Receptor 1 (TAAR1) is a G protein-coupled receptor expressed in the mammalian brain and known to influence subcortical monoaminergic transmission. Monoamines, such as dopamine, also play an important role within the prefrontal cortex (PFC) circuitry, which is critically involved in high-o5rder cognitive processes. TAAR1-selective ligands have shown potential antipsychotic, antidepressant, and pro-cognitive effects in experimental animal models; however, it remains unclear whether TAAR1 can affect PFC-related processes and functions. In this study, we document a distinct pattern of expression of TAAR1 in the PFC, as well as altered subunit composition and deficient functionality of the glutamate N-methyl-D-aspartate (NMDA) receptors in the pyramidal neurons of layer V of PFC in mice lacking TAAR1. The dysregulated cortical glutamate transmission in TAAR1-KO mice was associated with aberrant behaviors in several tests, indicating a perseverative and impulsive phenotype of mutants. Conversely, pharmacological activation of TAAR1 with selective agonists reduced premature impulsive responses observed in the fixed-interval conditioning schedule in normal mice. Our study indicates that TAAR1 plays an important role in the modulation of NMDA receptor-mediated glutamate transmission in the PFC and related functions. Furthermore, these data suggest that the development of TAAR1-based drugs could provide a novel therapeutic approach for the treatment of disorders related to aberrant cortical functions. PMID:25749299

  12. Age-related changes in anterior cingulate cortex glutamate in schizophrenia: A (1)H MRS Study at 7 Tesla.

    Science.gov (United States)

    Brandt, Allison S; Unschuld, Paul G; Pradhan, Subechhya; Lim, Issel Anne L; Churchill, Gregory; Harris, Ashley D; Hua, Jun; Barker, Peter B; Ross, Christopher A; van Zijl, Peter C M; Edden, Richard A E; Margolis, Russell L

    2016-04-01

    The extent of age-related changes in glutamate and other neurometabolites in the anterior cingulate cortex (ACC) in individuals with schizophrenia remain unclear. Magnetic resonance spectroscopy (MRS) at 7 T, which yields precise measurements of various metabolites and can distinguish glutamate from glutamine, was used to determine levels of ACC glutamate and other metabolites in 24 individuals with schizophrenia and 24 matched controls. Multiple regression analysis revealed that ACC glutamate decreased with age in patients but not controls. No changes were detected in levels of glutamine, N-acetylaspartate, N-acetylaspartylglutamic acid, myo-inositol, GABA, glutathione, total creatine, and total choline. These results suggest that age may be an important modifier of ACC glutamate in schizophrenia. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Interfacial bubbles formed by plunging thin liquid films in a pool

    Science.gov (United States)

    Salkin, Louis; Schmit, Alexandre; David, Richard; Delvert, Alexandre; Gicquel, Eric; Panizza, Pascal; Courbin, Laurent

    2017-06-01

    We show that the immersion of a horizontally suspended thin film of liquid in a pool of the same fluid creates an interfacial bubble, that is, a bubble at the liquid-air interface. Varying the fluid properties, the film's size, and its immersion velocity, our experiments unveil two formation regimes characterized by either a visco-capillary or an inertio-capillary mechanism that controls the size of a produced bubble. To rationalize these results, we compare the pressure exerted by the air flow under a plunging film with the Laplace pressure needed to generate film dimpling, which subsequently yields air entrapment and the production of a bubble. This physical model explains the power-law variations of the bubble size with the governing dimensionless number for each regime.

  14. POOL WATER TREATMENT AND COOLING SYSTEM DESCRIPTION DOCUMENT

    International Nuclear Information System (INIS)

    King, V.

    2000-01-01

    The Pool Water Treatment and Cooling System is located in the Waste Handling Building (WHB), and is comprised of various process subsystems designed to support waste handling operations. This system maintains the pool water temperature within an acceptable range, maintains water quality standards that support remote underwater operations and prevent corrosion, detects leakage from the pool liner, provides the capability to remove debris from the pool, controls the pool water level, and helps limit radiological exposure to personnel. The pool structure and liner, pool lighting, and the fuel staging racks in the pool are not within the scope of the Pool Water Treatment and Cooling System. Pool water temperature control is accomplished by circulating the pool water through heat exchangers. Adequate circulation and mixing of the pool water is provided to prevent localized thermal hotspots in the pool. Treatment of the pool water is accomplished by a water treatment system that circulates the pool water through filters, and ion exchange units. These water treatment units remove radioactive and non-radioactive particulate and dissolved solids from the water, thereby providing the water clarity needed to conduct waste handling operations. The system also controls pool water chemistry to prevent advanced corrosion of the pool liner, pool components, and fuel assemblies. Removal of radioactivity from the pool water contributes to the project ALARA (as low as is reasonably achievable) goals. A leak detection system is provided to detect and alarm leaks through the pool liner. The pool level control system monitors the water level to ensure that the minimum water level required for adequate radiological shielding is maintained. Through interface with a demineralized water system, adequate makeup is provided to compensate for loss of water inventory through evaporation and waste handling operations. Interface with the Site Radiological Monitoring System provides continuous

  15. Glufosinate aerogenic exposure induces glutamate and IL-1 receptor dependent lung inflammation.

    Science.gov (United States)

    Maillet, Isabelle; Perche, Olivier; Pâris, Arnaud; Richard, Olivier; Gombault, Aurélie; Herzine, Ameziane; Pichon, Jacques; Huaux, Francois; Mortaud, Stéphane; Ryffel, Bernhard; Quesniaux, Valérie F J; Montécot-Dubourg, Céline

    2016-11-01

    Glufosinate-ammonium (GLA), the active component of an herbicide, is known to cause neurotoxicity. GLA shares structural analogy with glutamate. It is a powerful inhibitor of glutamine synthetase (GS) and may bind to glutamate receptors. Since these potentials targets of GLA are present in lung and immune cells, we asked whether airway exposure to GLA may cause lung inflammation in mice. A single GLA exposure (1 mg/kg) induced seizures and inflammatory cell recruitment in the broncho-alveolar space, and increased myeloperoxidase (MPO), inducible NO synthase (iNOS), interstitial inflammation and disruption of alveolar septae within 6-24 h. Interleukin 1β (IL-1β) was increased and lung inflammation depended on IL-1 receptor 1 (IL-1R1). We demonstrate that glutamate receptor pathway is central, since the N-methyl-D-aspartate (NMDA) receptor inhibitor MK-801 prevented GLA-induced lung inflammation. Chronic exposure (0.2 mg/kg 3× per week for 4 weeks) caused moderate lung inflammation and enhanced airway hyperreactivity with significant increased airway resistance. In conclusion, GLA aerosol exposure causes glutamate signalling and IL-1R-dependent pulmonary inflammation with airway hyperreactivity in mice. © 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

  16. Working Memory Modulates Glutamate Levels in the Dorsolateral Prefrontal Cortex during 1H fMRS

    Directory of Open Access Journals (Sweden)

    Eric A. Woodcock

    2018-03-01

    Full Text Available Glutamate is involved in excitatory neurotransmission and metabolic processes related to brain function. Previous studies using proton functional magnetic resonance spectroscopy (1H fMRS have demonstrated elevated cortical glutamate levels by 2–4% during visual and motor stimulation, relative to periods of no stimulation. Here, we extended this approach to working memory cognitive task performance, which has been consistently associated with dorsolateral prefrontal cortex (dlPFC activation. Sixteen healthy adult volunteers completed a continuous visual fixation “rest” task followed by a letter 2-back working memory task during 1H fMRS acquisition of the left dlPFC, which encompassed Brodmann areas 45 and 46 over a 4.5-cm3 volume. Using a 100% automated fitting procedure integrated with LCModel, raw spectra were eddy current-, phase-, and shift-corrected prior to quantification resulting in a 32s temporal resolution or 8 averages per spectra. Task compliance was high (95 ± 11% correct and the mean Cramer-Rao Lower Bound of glutamate was 6.9 ± 0.9%. Relative to continuous passive visual fixation, left dlPFC glutamate levels were significantly higher by 2.7% (0.32 mmol/kg wet weight during letter 2-back performance. Elevated dlPFC glutamate levels reflect increased metabolic activity and excitatory neurotransmission driven by working memory-related cognitive demands. These results provide the first in vivo demonstration of elevated dlPFC glutamate levels during working memory.

  17. Measurements in large pool fires with an actively cooled calorimeter

    International Nuclear Information System (INIS)

    Koski, J.A.; Wix, S.D.

    1995-01-01

    The pool fire thermal test described in Safety Series 6 published by the International Atomic Energy Agency (IAEA) or Title 10, Code of Federal Regulations, Part 71 (10CFR71) in the United States is one of the most difficult tests that a container for larger ''Type B'' quantities of nuclear materials must pass. If retests of a container are required, costly redesign and project delays can result. Accurate measurements and modeling of the pool fire environment will ultimately lower container costs by assuring that containers past the pool fire test on the first attempt. Experiments indicate that the object size or surface temperature of the container can play a role in determining local heat fluxes that are beyond the effects predicted from the simple radiative heat transfer laws. An analytical model described by Nicolette and Larson 1990 can be used to understand many of these effects. In this model a gray gas represents soot particles present in the flame structure. Close to the container surface, these soot particles are convectively and radiatively cooled and interact with incident energy from the surrounding fire. This cooler soot cloud effectively prevents some thermal radiation from reaching the container surface, reducing the surface heat flux below the value predicted by a transparent medium model. With some empirical constants, the model suggested by Nicolette and Larson can be used to more accurately simulate the pool fire environment. Properly formulated, the gray gas approaches also fast enough to be used with standard commercial computer codes to analyze shipping containers. To calibrate this type of model, accurate experimental measurements of radiative absorption coefficients, flame temperatures, and other parameters are necessary. A goal of the calorimeter measurements described here is to obtain such parameters so that a fast, useful design tool for large pool fires can be constructed

  18. Glutamine synthetase activity and glutamate uptake in hippocampus and frontal cortex in portal hypertensive rats

    Science.gov (United States)

    Acosta, Gabriela Beatriz; Fernández, María Alejandra; Roselló, Diego Martín; Tomaro, María Luján; Balestrasse, Karina; Lemberg, Abraham

    2009-01-01

    AIM: To study glutamine synthetase (GS) activity and glutamate uptake in the hippocampus and frontal cortex (FC) from rats with prehepatic portal vein hypertension. METHODS: Male Wistar rats were divided into sham-operated group and a portal hypertension (PH) group with a regulated stricture of the portal vein. Animals were sacrificed by decapitation 14 d after portal vein stricture. GS activity was determined in the hippocampus and FC. Specific uptake of radiolabeled L-glutamate was studied using synaptosome-enriched fractions that were freshly prepared from both brain areas. RESULTS: We observed that the activity of GS increased in the hippocampus of PH rats, as compared to control animals, and decreased in the FC. A significant decrease in glutamate uptake was found in both brain areas, and was more marked in the hippocampus. The decrease in glutamate uptake might have been caused by a deficient transport function, significantly and persistent increase in this excitatory neurotransmitter activity. CONCLUSION: The presence of moderate ammonia blood levels may add to the toxicity of excitotoxic glutamate in the brain, which causes alterations in brain function. Portal vein stricture that causes portal hypertension modifies the normal function in some brain regions. PMID:19533812

  19. Altered expression patterns of group I and II metabotropic glutamate receptors in multiple sclerosis

    NARCIS (Netherlands)

    Geurts, J. J. G.; Wolswijk, G.; Bö, L.; van der Valk, P.; Polman, C. H.; Troost, D.; Aronica, E.

    2003-01-01

    Recent evidence supports a role for glutamate receptors in the pathophysiology of multiple sclerosis. In the present study, we have focused specifically on the expression of metabotropic glutamate receptors (mGluRs) in multiple sclerosis brain tissue. The expression of group I (mGluR1alpha and

  20. Effect of parental morphine addiction on extracellular glutamate concentration of dentate gyrus in rat offsprings

    Directory of Open Access Journals (Sweden)

    rahele Assaee

    2004-01-01

    Findings: In male offsprings of sham control1, sham control2, test1 and test2 basal and electrical stimulated of extracellular glutamate concentration of dentate gyrus were: 0.67±0.04, 1.11±0.1, and in female offsprings were 0.47±0.06, 0.88±0.05 (n=5. The basal and stimulated extra cellular glutamate concentration of dentate gyrus was decreased in both test1 and test2 offsprings. It was less in test1 than test2 offsprings. The glutamate concentration of dentate gyrus in female offsprings of test1 group was less than that of the male offsprings. conclusion: The results suggest that parental morphine addiction may cause learning deficiency through reduction of extracellular glutamate concentration in dentate gyrus so the side effects of parental morphine addiction in offsprings must be considered.

  1. Glutamate transporter activity promotes enhanced Na+/K+-ATPase -mediated extracellular K+ management during neuronal activity

    DEFF Research Database (Denmark)

    Larsen, Brian R; Holm, Rikke; Vilsen, Bente

    2016-01-01

    , in addition, Na+ /K+ -ATPase-mediated K+ clearance could be governed by astrocytic [Na+ ]i . During most neuronal activity, glutamate is released in the synaptic cleft and is re-absorbed by astrocytic Na+ -coupled glutamate transporters, thereby elevating [Na+ ]i . It thus remains unresolved whether...... the different Na+ /K+ -ATPase isoforms are controlled by [K+ ]o or [Na+ ]i during neuronal activity. Hippocampal slice recordings of stimulus-induced [K+ ]o transients with ion-sensitive microelectrodes revealed reduced Na+ /K+ -ATPase-mediated K+ management upon parallel inhibition of the glutamate transporter......+ affinity to the α1 and α2 isoforms than the β2 isoform. In summary, enhanced astrocytic Na+ /K+ -ATPase-dependent K+ clearance was obtained with parallel glutamate transport activity. The astrocytic Na+ /K+ -ATPase isoform constellation α2β1 appeared to be specifically geared to respond to the [Na+ ]i...

  2. [Imbalance of system of glutamin - glutamic acid in the placenta and amniotic fluid at placental insufficiency].

    Science.gov (United States)

    Pogorelova, T N; Gunko, V O; Linde, V A

    2014-01-01

    Metabolism of glutamine and glutamic acid has been investigated in the placenta and amniotic fluid under conditions of placental insufficiency. The development of placental insufficiency is characterized by the increased content of glutamic acid and a decrease of glutamine in both placenta and amniotic fluid. These changes changes were accompanied by changes in the activity of enzymes involved in the metabolism of these amino acids. There was a decrease in glutamate dehydrogenase activity and an increase in glutaminase activity with the simultaneous decrease of glutamine synthetase activity. The compensatory decrease in the activity of glutamine keto acid aminotransferase did not prevent a decrease in the glutamine level. The impairments in the system glutamic acid-glutamine were more pronounced during the development of premature labor.

  3. Rapid purification and plasticization of D-glutamate-containing poly-γ-glutamate from Japanese fermented soybean food natto.

    Science.gov (United States)

    Ashiuchi, Makoto; Oike, Shota; Hakuba, Hirofumi; Shibatani, Shigeo; Oka, Nogiho; Wakamatsu, Taisuke

    2015-12-10

    Poly-γ-glutamate (PGA) is a major component of mucilage derived from natto, a Japanese fermented food made from soybeans, and PGAs obtained under laboratory's conditions contain numerous d-glutamyl residues. Natto foods are thus promising as a source for nutritionally safe d-amino acids present in intact and digested polymers, although there is little information on the stereochemistry of PGA isolated directly from natto. Here, we describe the development of a new process for rapid purification of PGA using alum and determined the D-glutamate content of natto PGA by chiral high-performance liquid chromatographic analysis. Further, using hexadecylpyridinium cation (HDP(+)), which is a compound of toothpaste, we chemically transformed natto PGA into a new thermoplastic material, called DL-PGAIC. (1)H nuclear magnetic resonance and calorimetric measurements indicate that DL-PGAIC is a stoichiometric complex of natto PGA and HDP(+) with glass transition points of -16.8 °C and -3.1 °C. Then, DL-PGAIC began decomposing at 210°C, suggesting thermal stability suitable for use as a supramolecular soft plastic. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Pool scrubbing models for iodine components

    Energy Technology Data Exchange (ETDEWEB)

    Fischer, K [Battelle Ingenieurtechnik GmbH, Eschborn (Germany)

    1996-12-01

    Pool scrubbing is an important mechanism to retain radioactive fission products from being carried into the containment atmosphere or into the secondary piping system. A number of models and computer codes has been developed to predict the retention of aerosols and fission product vapours that are released from the core and injected into water pools of BWR and PWR type reactors during severe accidents. Important codes in this field are BUSCA, SPARC and SUPRA. The present paper summarizes the models for scrubbing of gaseous Iodine components in these codes, discusses the experimental validation, and gives an assessment of the state of knowledge reached and the open questions which persist. The retention of gaseous Iodine components is modelled by the various codes in a very heterogeneous manner. Differences show up in the chemical species considered, the treatment of mass transfer boundary layers on the gaseous and liquid sides, the gas-liquid interface geometry, calculation of equilibrium concentrations and numerical procedures. Especially important is the determination of the pool water pH value. This value is affected by basic aerosols deposited in the water, e.g. Cesium and Rubidium compounds. A consistent model requires a mass balance of these compounds in the pool, thus effectively coupling the pool scrubbing phenomena of aerosols and gaseous Iodine species. Since the water pool conditions are also affected by drainage flow of condensate water from different regions in the containment, and desorption of dissolved gases on the pool surface is determined by the gas concentrations above the pool, some basic limitations of specialized pool scrubbing codes are given. The paper draws conclusions about the necessity of coupling between containment thermal-hydraulics and pool scrubbing models, and proposes ways of further simulation model development in order to improve source term predictions. (author) 2 tabs., refs.

  5. Pool scrubbing models for iodine components

    International Nuclear Information System (INIS)

    Fischer, K.

    1996-01-01

    Pool scrubbing is an important mechanism to retain radioactive fission products from being carried into the containment atmosphere or into the secondary piping system. A number of models and computer codes has been developed to predict the retention of aerosols and fission product vapours that are released from the core and injected into water pools of BWR and PWR type reactors during severe accidents. Important codes in this field are BUSCA, SPARC and SUPRA. The present paper summarizes the models for scrubbing of gaseous Iodine components in these codes, discusses the experimental validation, and gives an assessment of the state of knowledge reached and the open questions which persist. The retention of gaseous Iodine components is modelled by the various codes in a very heterogeneous manner. Differences show up in the chemical species considered, the treatment of mass transfer boundary layers on the gaseous and liquid sides, the gas-liquid interface geometry, calculation of equilibrium concentrations and numerical procedures. Especially important is the determination of the pool water pH value. This value is affected by basic aerosols deposited in the water, e.g. Cesium and Rubidium compounds. A consistent model requires a mass balance of these compounds in the pool, thus effectively coupling the pool scrubbing phenomena of aerosols and gaseous Iodine species. Since the water pool conditions are also affected by drainage flow of condensate water from different regions in the containment, and desorption of dissolved gases on the pool surface is determined by the gas concentrations above the pool, some basic limitations of specialized pool scrubbing codes are given. The paper draws conclusions about the necessity of coupling between containment thermal-hydraulics and pool scrubbing models, and proposes ways of further simulation model development in order to improve source term predictions. (author) 2 tabs., refs

  6. Factors driving semi-aquatic predator occurrence in traditional cattle drinking pools: conservation issues

    Directory of Open Access Journals (Sweden)

    Raoul Manenti

    2016-08-01

    Full Text Available In several cases, human impact on water bodies and on their freshwater communities is detrimental, but in some cases the human activity may favour and enhance the biodiversity of small water bodies, as traditional cattle drinking pools. Despite their small size, small water bodies may constitute hot spot of biodiversity often representing the only lentic aquatic biotope in landscapes where superficial water lacks or flows in lotic environments like creeks and streams. Predators are good indicators of biodiversity in ponds and give information of food chain web complexity. In particular, semi-aquatic predators like amphibians and dragonflies may account for a substantial percentage of energy flow between aquatic and terrestrial ecosystems. In this study, we evaluated the conservation value of traditional cattle drinking pools building by assessing the factors determining the occurrence and distribution of the semi-aquatic predators. From April to August 2015, we investigated 30 distinct pools recording several abiotic and biotic environmental variables. We detected 4 semi-aquatic predators: Salamandra salamandra larvae, Triturus carnifex, Aeshna sp. larvae and Libellula sp. larvae. Abiotic features played a major role in shaping the predator community that resulted linked to stable, with no dryness period, and large drinking pools. Invertebrate prey biomass was not particularly important, while vegetation cover and occurrence of unpalatable tadpoles were the most important biotic features of the pools. Our study provides novel evidence on the importance of cattle drinking pools management to preserve biodiversity especially in areas where traditional pastoral activity is disappearing.

  7. Conformation of poly(γ-glutamic acid) in aqueous solution.

    Science.gov (United States)

    Muroga, Yoshio; Nakaya, Asami; Inoue, Atsuki; Itoh, Daiki; Abiru, Masaya; Wada, Kaori; Takada, Masako; Ikake, Hiroki; Shimizu, Shigeru

    2016-04-01

    Local conformation and overall conformation of poly(γ-DL-glutamic acid) (PγDLGA) and poly(γ-L-glutamic acid) (PγLGA) in aqueous solution was studied as a function of degree of ionization ε by (1) H-NMR, circular dichroism, and potentiometric titration. It was clarified that their local conformation is represented by random coil over an entire ε range and their overall conformation is represented by expanded random-coil in a range of ε > ε(*) , where ε(*) is about 0.3, 0.35, 0.45, and 0.5 for added-salt concentration of 0.02M, 0.05M, 0.1M, and 0.2M, respectively. In a range of ε acidic media. © 2015 Wiley Periodicals, Inc.

  8. Self-formed waterfall plunge pools in homogeneous rock

    Science.gov (United States)

    Scheingross, Joel S.; Lo, Daniel Y.; Lamb, Michael P.

    2017-01-01

    Waterfalls are ubiquitous, and their upstream propagation can set the pace of landscape evolution, yet no experimental studies have examined waterfall plunge pool erosion in homogeneous rock. We performed laboratory experiments, using synthetic foam as a bedrock simulant, to produce self-formed waterfall plunge pools via particle impact abrasion. Plunge pool vertical incision exceeded lateral erosion by approximately tenfold until pools deepened to the point that the supplied sediment could not be evacuated and deposition armored the pool bedrock floor. Lateral erosion of plunge pool sidewalls continued after sediment deposition, but primarily at the downstream pool wall, which might lead to undermining of the plunge pool lip, sediment evacuation, and continued vertical pool floor incision in natural streams. Undercutting of the upstream pool wall was absent, and our results suggest that vertical drilling of successive plunge pools is a more efficient waterfall retreat mechanism than the classic model of headwall undercutting and collapse in homogeneous rock.

  9. Glutamate uptake is important for osmoregulation and survival in the rice pathogen Burkholderia glumae.

    Directory of Open Access Journals (Sweden)

    Yongsung Kang

    Full Text Available Bacteria exhibit an optimal growth rate in culture media with sufficient nutrients at an optimal temperature and pH. In addition, the concentration of solutes plays a critical role in bacterial growth and survival. Glutamate is known to be a major anionic solute involved in osmoregulation and the bacterial cell's response to changes in solute concentration. To determine how glutamate uptake is involved in osmoregulation in the rice bacterial pathogen Burkholderia glumae BGR1, we mutated the gltI gene encoding a periplasmic substrate binding protein of a glutamate transport system to abolish glutamate uptake, and monitored the growth of the gltI null mutant in Luria-Bertani medium. We found that the gltI null mutant showed a slower growth rate than the wild-type strain and experienced hyperosmotic stress resulting in water loss from the cytoplasm in stationary phase. When the incubation time was extended, the mutant population collapsed due to the hyperosmotic stress. The gltI null mutant exhibited loss of adaptability under both hypoosmotic and hyperosmotic stresses. The growth rate of the gltI null mutant was restored to the level of wild-type growth by exogenous addition of glycine betaine to the culture medium, indicating that glycine betaine is a compatible solute in B. glumae. These results indicate that glutamate uptake from the environment plays a key role in osmoregulation in B. glumae.

  10. Thermal analysis and modeling of a swimming pool heating system by utilizing waste energy rejected from a chiller unit of an ice rink

    Directory of Open Access Journals (Sweden)

    Kuyumcu Muhammed Enes

    2017-01-01

    Full Text Available This study deals with the thermal analysis and modeling of a swimming pool heating system in which the waste energy rejected from the chiller unit of an ice rink is used as an energy source. The system consists of a swimming pool and an ice rink coupled by a chiller unit. The swimming pool and the ice rink both indoor types and were constructed in city of Gaziantep, Turkey. The thermal energy requirement for each section is determined by thermal analysis of each component of the system. Effects of different design parameters such as ceiling insulation thickness, ceiling emissivity, Carnot efficiency factor and size of the ice rink on the thermal energy requirements and coefficient of performance of the chiller unit are investigated. As a result of analyses of the system, the minimum ice rink area is determined in order to meet annual total heat energy demand of the olympic-sized swimming pool.

  11. Synthesis and pharmacological evaluation of conformationally constrained glutamic acid higher homologues

    DEFF Research Database (Denmark)

    Tamborini, Lucia; Cullia, Gregorio; Nielsen, Birgitte

    2016-01-01

    Homologation of glutamic acid chain together with conformational constraint is a commonly used strategy to achieve selectivity towards different types of glutamate receptors. In the present work, starting from two potent and selective unnatural amino acids previously developed by us, we...... investigated the effects on the activity/selectivity profile produced by a further increase in the distance between the amino acidic moiety and the distal carboxylate group. Interestingly, the insertion of an aromatic ring as a spacer produced a low micromolar affinity NMDA ligand that might represent a lead...

  12. The glutamate-glutamine(GABA cycle: importance of late postnatal development and potential reciprocal interactions between biosynthesis and degradation

    Directory of Open Access Journals (Sweden)

    Leif eHertz

    2013-05-01

    Full Text Available The gold standard for studies of glutamate-glutamine(GABA cycling and its connections to brain biosynthesis from glucose of glutamate and GABA and their subsequent metabolism are the elegant in vivo studies by 13C magnetic resonance spectroscopy (NMR, showing the large fluxes in the cycle. However, simpler experiments in intact brain tissue (e.g. immunohistochemistry, brain slices, cultured brain cells and mitochondria have also made important contributions to the understanding of details, mechanisms and functional consequences of glutamate/GABA biosynthesis and degradation. The purpose of this review is to attempt to integrate evidence from different sources regarding i the enzyme(s responsible for the initial conversion of -ketoglutarate to glutamate; ii the possibility that especially glutamate oxidation is essentially confined to astrocytes; and iii the ontogenetically very late onset and maturation of glutamine-glutamate(GABA cycle function. Pathway models based on the functional importance of aspartate for glutamate synthesis suggest the possibility of interacting pathways for biosynthesis and degradation of glutamate and GABA and the use of transamination as the default mechanism for initiation of glutamate oxidation. The late development and maturation are related to the late cortical gliogenesis and convert brain cortical function from being purely neuronal to becoming neuronal-astrocytic. This conversion is associated with huge increases in energy demand and production, and the character of potentially incurred gains of function are discussed. These may include alterations in learning mechanisms, in mice indicated by lack of pairing of odor learning with aversive stimuli in newborn animals but the development of such an association 10-12 days later. The possibility is suggested that analogous maturational changes may contribute to differences in the way learning is accomplished in the newborn human brain and during later development.

  13. Role of Na,K-ATPase α1 and α2 isoforms in the support of astrocyte glutamate uptake.

    Directory of Open Access Journals (Sweden)

    Nina B Illarionova

    Full Text Available Glutamate released during neuronal activity is cleared from the synaptic space via the astrocytic glutamate/Na(+ co-transporters. This transport is driven by the transmembrane Na(+ gradient mediated by Na,K-ATPase. Astrocytes express two isoforms of the catalytic Na,K-ATPase α subunits; the ubiquitously expressed α1 subunit and the α2 subunit that has a more specific expression profile. In the brain α2 is predominantly expressed in astrocytes. The isoforms differ with regard to Na+ affinity, which is lower for α2. The relative roles of the α1 and α2 isoforms in astrocytes are not well understood. Here we present evidence that the presence of the α2 isoform may contribute to a more efficient restoration of glutamate triggered increases in intracellular sodium concentration [Na(+]i. Studies were performed on primary astrocytes derived from E17 rat striatum expressing Na,K-ATPase α1 and α2 and the glutamate/Na(+ co-transporter GLAST. Selective inhibition of α2 resulted in a modest increase of [Na(+]i accompanied by a disproportionately large decrease in uptake of aspartate, an indicator of glutamate uptake. To compare the capacity of α1 and α2 to handle increases in [Na(+]i triggered by glutamate, primary astrocytes overexpressing either α1 or α2 were used. Exposure to glutamate 200 µM caused a significantly larger increase in [Na(+]i in α1 than in α2 overexpressing cells, and as a consequence restoration of [Na(+]i, after glutamate exposure was discontinued, took longer time in α1 than in α2 overexpressing cells. Both α1 and α2 interacted with astrocyte glutamate/Na(+ co-transporters via the 1st intracellular loop.

  14. Patent pools: Intellectual property rights and competition.

    NARCIS (Netherlands)

    Rodriguez, V.F.

    2010-01-01

    Patent pools do not correct all problems associated with patent thickets. In this respect, patent pools might not stop the outsider problem from striking pools. Moreover, patent pools can be expensive to negotiate, can exclude patent holders with smaller numbers of patents or enable a group of major

  15. A comparative analysis of DNA barcode microarray feature size

    Directory of Open Access Journals (Sweden)

    Smith Andrew M

    2009-10-01

    Full Text Available Abstract Background Microarrays are an invaluable tool in many modern genomic studies. It is generally perceived that decreasing the size of microarray features leads to arrays with higher resolution (due to greater feature density, but this increase in resolution can compromise sensitivity. Results We demonstrate that barcode microarrays with smaller features are equally capable of detecting variation in DNA barcode intensity when compared to larger feature sizes within a specific microarray platform. The barcodes used in this study are the well-characterized set derived from the Yeast KnockOut (YKO collection used for screens of pooled yeast (Saccharomyces cerevisiae deletion mutants. We treated these pools with the glycosylation inhibitor tunicamycin as a test compound. Three generations of barcode microarrays at 30, 8 and 5 μm features sizes independently identified the primary target of tunicamycin to be ALG7. Conclusion We show that the data obtained with 5 μm feature size is of comparable quality to the 30 μm size and propose that further shrinking of features could yield barcode microarrays with equal or greater resolving power and, more importantly, higher density.

  16. Mercury concentrations and pools in four adjacent coniferous and deciduous upland forests in Beijing, China

    Science.gov (United States)

    Zhou, Jun; Wang, Zhangwei; Zhang, Xiaoshan; Gao, Yu

    2017-05-01

    Understanding of forest mercury (Hg) pools is important for quantifying the global atmospheric Hg removal. We studied gaseous elemental Hg (GEM) concentrations, litterfall Hg depositions, and pool sizes in four adjacent stands at Mount Dongling to assess Hg dynamics in the forested catchment and the potential of Hg release during wildfires. The average GEM concentration was 2.5 ± 0.5 ng m-3, about 1.5 times of the background levels in the Northern Hemisphere. In all four stands, Hg concentrations increase in the following order: bole wood mineral soil litter < Oe soil < Oa organic soil. The Hg pools of aboveground biomass were comparable in the forests of larch, oak, and Chinese pine, which were much greater than that of mixed broadleaf stands due to lower biomass. The total Hg pools in ecosystems were similar in the four stands, because of the comparable Hg pool in the soil horizons (0-40 cm), which accounted for over 97% of the total ecosystem Hg storage in the four stands. Although Hg pools of the forest ecosystem in north China were comparable to North America and North Europe, Hg storage in forests constituted a high threat for large Hg emission pulses to the atmosphere by wildfires. The potential Hg emissions from the combustion at the four stands were ranged from 0.675 to 1.696 mg m-2.

  17. A combined approach of generalized additive model and bootstrap with small sample sets for fault diagnosis in fermentation process of glutamate.

    Science.gov (United States)

    Liu, Chunbo; Pan, Feng; Li, Yun

    2016-07-29

    Glutamate is of great importance in food and pharmaceutical industries. There is still lack of effective statistical approaches for fault diagnosis in the fermentation process of glutamate. To date, the statistical approach based on generalized additive model (GAM) and bootstrap has not been used for fault diagnosis in fermentation processes, much less the fermentation process of glutamate with small samples sets. A combined approach of GAM and bootstrap was developed for the online fault diagnosis in the fermentation process of glutamate with small sample sets. GAM was first used to model the relationship between glutamate production and different fermentation parameters using online data from four normal fermentation experiments of glutamate. The fitted GAM with fermentation time, dissolved oxygen, oxygen uptake rate and carbon dioxide evolution rate captured 99.6 % variance of glutamate production during fermentation process. Bootstrap was then used to quantify the uncertainty of the estimated production of glutamate from the fitted GAM using 95 % confidence interval. The proposed approach was then used for the online fault diagnosis in the abnormal fermentation processes of glutamate, and a fault was defined as the estimated production of glutamate fell outside the 95 % confidence interval. The online fault diagnosis based on the proposed approach identified not only the start of the fault in the fermentation process, but also the end of the fault when the fermentation conditions were back to normal. The proposed approach only used a small sample sets from normal fermentations excitements to establish the approach, and then only required online recorded data on fermentation parameters for fault diagnosis in the fermentation process of glutamate. The proposed approach based on GAM and bootstrap provides a new and effective way for the fault diagnosis in the fermentation process of glutamate with small sample sets.

  18. Ketamine and other glutamate receptor modulators for depression in adults.

    Science.gov (United States)

    Caddy, Caroline; Amit, Ben H; McCloud, Tayla L; Rendell, Jennifer M; Furukawa, Toshi A; McShane, Rupert; Hawton, Keith; Cipriani, Andrea

    2015-09-23

    , mild-moderate depression. Nine studies recruited only treatment-resistant patients.We rated the risk of bias as low or unclear for most domains, though lack of detail regarding masking of treatment in the studies reduced our certainty in the effect for all outcomes. We rated three studies as having high risk for selective outcome reporting. Many trials did not provide information on all the prespecified outcomes and we found no data, or very limited data, on very important issues like suicidality, cognition, quality of life, costs to healthcare services and dropouts due to lack of efficacy.Among all glutamate receptor modulators, only ketamine (administered intravenously) proved to be more efficacious than placebo, though the quality of evidence was limited by risk of bias and small sample sizes. There was low quality evidence that treatment with ketamine increased the likelihood of response after 24 hours (odds ratio (OR) 10.77, 95% confidence interval (CI) 2.00 to 58.00; 3 RCTs, 56 participants), 72 hours (OR 12.59, 95% CI 2.38 to 66.73; 3 RCTs, 56 participants), and one week (OR 2.58, 95% CI 1.08 to 6.16; 4 RCTs, 131 participants). The effect of ketamine was even less certain at two weeks, as data were available from only one trial (OR 0.93, 95% CI 0.31 to 2.83; 51 participants, low quality evidence). This was consistent across all efficacy outcomes. Ketamine caused more confusion and emotional blunting compared to placebo. There was insufficient evidence to determine if this increased the likelihood of leaving the study early (OR 1.90, 95% CI 0.43 to 8.47; 5 RCTs, 139 participants, low quality evidence).One RCT with 72 participants reported higher numbers of responders on ketamine than midazolam at 24 hours (OR 0.36, 95% CI 0.14 to 0.58), 72 hours (OR 0.37, 95% CI 0.16 to 0.59), and one week (OR 0.29, 95% CI 0.08 to 0.49). However, midazolam was better tolerated than ketamine in terms of blurred vision, dizziness, general malaise and nausea/vomiting at 24 hours

  19. Predicting the emissive power of hydrocarbon pool fires

    International Nuclear Information System (INIS)

    Munoz, Miguel; Planas, Eulalia; Ferrero, Fabio; Casal, Joaquim

    2007-01-01

    The emissive power (E) of a flame depends on the size of the fire and the type of fuel. In fact, it changes significantly over the flame surface: the zones of luminous flame have high emittance, while those covered by smoke have low E values. The emissive power of each zone (that is, the luminous or clear flame and the non-luminous or smoky flame) and the portion of total flame area they occupy must be assessed when a two-zone model is used. In this study, data obtained from an experimental set-up were used to estimate the emissive power of fires and its behaviour as a function of pool size. The experiments were performed using gasoline and diesel oil as fuel. Five concentric circular pools (1.5, 3, 4, 5 and 6 m in diameter) were used. Appropriate instruments were employed to determine the main features of the fires. By superimposing IR and VHS images it was possible to accurately identify the luminous and non-luminous zones of the fire. Mathematical expressions were obtained that give a more accurate prediction of E lum , E soot and the average emissive power of a fire as a function of its luminous and smoky zones. These expressions can be used in a two-zone model to obtain a better prediction of the thermal radiation. The value of the radiative fraction was determined from the thermal flux measured with radiometers. An expression is also proposed for estimating the radiative fraction

  20. Effect of turbulent natural convection on sodium pool combustion in the steam generator building of a fast breeder reactor

    International Nuclear Information System (INIS)

    Karthikeyan, S.; Sundararajan, T.; Shet, U.S.P.; Selvaraj, P.

    2009-01-01

    A computational model is proposed to simulate sodium pool combustion considering the effect of turbulent natural convection in a vented enclosure of the steam generator building (SGB) of a fast breeder reactor. The model is validated by comparing the simulated results with the experimental results available in literature for sodium pool combustion in a CSTF vessel. After validation, the effects of vents and the location of the pool on the burning rate of sodium and the associated heat transfer to the walls are studied in an enclosure comparable in size to one floor of the steam generator building. In the presence of ventilation, the burning rate of sodium increases, but the total heat transferred to the walls of the enclosure is reduced. It is also found that the burning rate of sodium pool and the heat transfer to the walls of the enclosures vary significantly with the location of sodium pool.