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Sample records for gamma-aminobutyric acidb responses

  1. The anticonvulsant gabapentin (neurontin) does not act through gamma-aminobutyric acid-B receptors

    DEFF Research Database (Denmark)

    Jensen, Anders A.; Mosbacher, Johannes; Elg, Susanne

    2002-01-01

    The actions of the anticonvulsant gabapentin [1-(aminomethyl)cyclohexaneacetic acid, Neurontin] have been somewhat enigmatic until recently, when it was claimed to be a gamma-aminobutyric acid-B (GABA(B)) receptor agonist acting exclusively at a heterodimeric complex containing the GABA(B(1a)) sp...

  2. A functional assay to measure postsynaptic gamma-aminobutyric acidB responses in cultured spinal cord neurons: Heterologous regulation of the same K+ channel

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    Kamatchi, G.L.; Ticku, M.K. (Univ. of Texas Health Science Center, San Antonio (USA))

    1991-02-01

    The stimulation of postsynaptic gamma-aminobutyric acid (GABA)B receptors leads to slow inhibitory postsynaptic potentials due to the influx of K(+)-ions. This was studied biochemically, in vitro in mammalian cultured spinal cord neurons by using 86Rb as a substitute for K+. (-)-Baclofen, a GABAB receptor agonist, produced a concentration-dependent increase in the 86Rb-influx. This effect was stereospecific and blocked by GABAB receptor antagonists like CGP 35 348 (3-aminopropyl-diethoxymethyl-phosphonic acid) and phaclofen. Apart from the GABAB receptors, both adenosine via adenosine1 receptors and 5-hydroxytryptamine (5-HT) via 5-HT1 alpha agonists also increased the 86Rb-influx. These agonists failed to show any additivity between them when they were combined in their maximal concentration. In addition, their effect was antagonized specifically by their respective antagonists without influencing the others. These findings suggest the presence of GABAB, adenosine1 and 5-HT1 alpha receptors in the cultured spinal cord neurons, which exhibit a heterologous regulation of the same K(+)-channel. The effect of these agonists were antagonized by phorbol 12,13-didecanoate, an activator of protein kinase C, and pretreatment with pertussis toxin. This suggests that these agonists by acting on their own receptors converge on the same K(+)-channel through the Gi/Go proteins. In summary, we have developed a biochemical functional assay for studying and characterizing GABAB synaptic pharmacology in vitro, using spinal cord neurons.

  3. Altered behavioral responses to gamma-aminobutyric acid pharmacological agents in a mouse model of Huntington's disease.

    Science.gov (United States)

    Hsu, Yi-Ting; Chang, Ya-Gin; Chang, Ching-Pang; Siew, Jian-Jing; Chen, Hui-Mei; Tsai, Chon-Haw; Chern, Yijuang

    2017-11-01

    Disruptions in gamma-aminobutyric (GABA) acid signaling are believed to be involved in Huntington's disease pathogenesis, but the regulation of GABAergic signaling remains elusive. Here we evaluated GABAergic signaling by examining the function of GABAergic drugs in Huntington's disease and the expression of GABAergic molecules using mouse models and human brain tissues from Huntington's disease. We treated wild-type and R6/2 mice (a transgenic Huntington's disease mouse model) acutely with vehicle, diazepam, or gaboxadol (drugs that selectively target synaptic or extrasynaptic GABA A receptors) and monitored their locomotor activity. The expression levels of GABA A receptors and a major neuron-specific chloride extruder (potassium-chloride cotransporter-2) were analyzed by real-time quantitative polymerase chain reaction, Western blot, and immunocytochemistry. The R6/2 mice were less sensitive to the sedative effects of both drugs, suggesting reduced function of GABA A receptors. Consistently, the expression levels of α1/α2 and δ subunits were lower in the cortex and striatum of R6/2 mice. Similar results were also found in 2 other mouse models of Huntington's disease and in Huntington's disease patients. Moreover, the interaction and expression levels of potassium-chloride cotransporter-2 and its activator (brain-type creatine kinase) were decreased in Huntington's disease neurons. These findings collectively suggest impaired chloride homeostasis, which further dampens GABA A receptor-mediated inhibitory signaling in Huntington's disease brains. The dysregulated GABAergic responses and altered expression levels of GABA A receptors and potassium-chloride cotransporter-2 in Huntington's disease mice appear to be authentic and may contribute to the clinical manifestations of Huntington's disease patients. © 2017 International Parkinson and Movement Disorder Society. © 2017 International Parkinson and Movement Disorder Society.

  4. Gene knockout of the alpha6 subunit of the gamma-aminobutyric acid type A receptor: lack of effect on responses to ethanol, pentobarbital, and general anesthetics.

    Science.gov (United States)

    Homanics, G E; Ferguson, C; Quinlan, J J; Daggett, J; Snyder, K; Lagenaur, C; Mi, Z P; Wang, X H; Grayson, D R; Firestone, L L

    1997-04-01

    The alpha6 subunit of the gamma-aminobutyric acid type A receptor (GABA(A)-R) has been implicated in mediating the intoxicating effects of ethanol and the motor ataxic effects of general anesthetics. To test this hypothesis, we used gene targeting in embryonic stem cells to create mice lacking a functional alpha6 gene. Homozygous mice are viable and fertile and have grossly normal cerebellar cytoarchitecture. Northern blot and reverse transcriptase-polymerase chain reaction analyses demonstrated that the targeting event disrupted production of functional alpha6 mRNA. Autoradiography of histological sections of adult brains demonstrated that diazepam-insensitive binding of [3H]Ro15-4513 to the cerebellar granule cell layer of wild-type mice was completely absent in homozygous mice. Cerebellar GABA(A)-R density was unchanged in the mutant mice; however, the apparent affinity for muscimol was markedly reduced. Sleep time response to injection of ethanol after pretreatment with vehicle or Ro15-4513 did not differ between genotypes. Sleep time response to injection of pentobarbital and loss of righting reflex and response to tail clamp stimulus in mice anesthetized with volatile anesthetics also did not differ between genotypes. Thus, the alpha6 subunit of the GABA(A)-R is not required for normal development, viability, and fertility and does not seem to be a critical or unique component of the neuronal pathway mediating the hypnotic effect of ethanol and its antagonism by Ro15-4513 in mice. Similarly, the alpha6 subunit does not seem to be involved in the behavioral responses to general anesthetics or pentobarbital.

  5. Effects of gamma-aminobutyric acid on the Hering-Breuer inspiration-inhibiting reflex.

    Science.gov (United States)

    Aleksandrova, N P; Aleksandrov, V G; Ivanova, T G

    2010-02-01

    Acute experiments on rats were performed to study the effects of intraventricular microinjections of gamma-aminobutyric acid (GABA) on the volume-time parameters of external respiration and the inspiration-inhibiting Hering-Breuer reflex. The state of this reflex before and after GABA administration was assessed in terms of the extent of changes in the duration and amplitude of inspiratory oscillations in intrathoracic pressure in response to end-expiratory occlusion of the trachea. Administration of 20 microM GABA into the lateral ventricles of the brain decreased the minute ventilation (due to reductions in the respiratory frequency and respiratory volume), weakened respiratory muscle contractions, and decreased the peak airflow rate on inspiration and expiration. The response to end-expiratory occlusion decreased significantly after administration of GABA, demonstrating the involvement of GABAergic mechanisms in mediating the inspiration-inhibiting Hering-Breuer reflex.

  6. Gamma-aminobutyric acid mediates nicotine biosynthesis in tobacco under flooding stress

    Directory of Open Access Journals (Sweden)

    Xiaoming Zhang

    2016-02-01

    Full Text Available Gamma-aminobutyric acid (GABA is a four-carbon non-protein amino acid conserved from bacteria to plants and vertebrates. Increasing evidence supports a regulatory role for GABA in plant development and the plant's response to environmental stress. The biosynthesis of nicotine, the main economically important metabolite in tobacco, is tightly regulated. GABA has not hitherto been reported to function in nicotine biosynthesis. Here we report that water flooding treatment (hypoxia markedly induced the accumulation of GABA and stimulated nicotine biosynthesis. Suppressing GABA accumulation by treatment with glutamate decarboxylase inhibitor impaired flooding-induced nicotine biosynthesis, while exogenous GABA application directly induced nicotine biosynthesis. Based on these results, we propose that GABA triggers nicotine biosynthesis in tobacco seedlings subjected to flooding. Our results provide insight into the molecular mechanism of nicotine biosynthesis in tobacco plants exposed to environmental stress.

  7. Detection of the in vivo conversion of 2-pyrrolidinone to gamma-aminobutyric acid in mouse brain.

    Science.gov (United States)

    Callery, P S; Stogniew, M; Geelhaar, L A

    1979-01-01

    Labeled gamma-aminobutyric acid was detected in mouse brain following intravenous injections of deuterium labeled 2-pyrrolidinone. [2H6]Pyrrolidinone was prepared by the reduction of [2H4]succinimide with lithium aluminum deuteride. Quantification was accomplished by a gas chromatography mass spectrometry assay method. gamma-Aminobutyric acid and internal standard, 5-aminovaleric acid, were converted to volatile derivatives by treatment with N,N-dimethylformamide dimethyl acetal. Quantitative estimates were derived from peak area measurements obtained from monitoring the parent ions of the gamma-aminobutyric acid and internal standard derivatives by repetitive scanning during the GC run. The conversion of pyrrolidinone to gamma-aminobutyric acid may provide a method for labeling central gamma-aminobutyric acid pools.

  8. Substrate-Na{sup +} complex formation: Coupling mechanism for {gamma}-aminobutyrate symporters

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    Pallo, Anna; Simon, Agnes [Department of Neurochemistry, Institute of Biomolecular Chemistry, Chemical Research Center, Hungarian Academy of Sciences (Hungary); Bencsura, Akos [Department of Theoretical Chemistry, Institute of Structural Chemistry, Chemical Research Center, Hungarian Academy of Sciences, Budapest (Hungary); Heja, Laszlo [Department of Neurochemistry, Institute of Biomolecular Chemistry, Chemical Research Center, Hungarian Academy of Sciences (Hungary); Kardos, Julianna, E-mail: jkardos@chemres.hu [Department of Neurochemistry, Institute of Biomolecular Chemistry, Chemical Research Center, Hungarian Academy of Sciences (Hungary)

    2009-07-24

    Crystal structures of transmembrane transport proteins belonging to the important families of neurotransmitter-sodium symporters reveal how they transport neurotransmitters across membranes. Substrate-induced structural conformations of gated neurotransmitter-sodium symporters have been in the focus of research, however, a key question concerning the mechanism of Na{sup +} ion coupling remained unanswered. Homology models of human glial transporter subtypes of the major inhibitory neurotransmitter {gamma}-aminobutyric acid were built. In accordance with selectivity data for subtype 2 vs. 3, docking and molecular dynamics calculations suggest similar orthosteric substrate (inhibitor) conformations and binding crevices but distinguishable allosteric Zn{sup 2+} ion binding motifs. Considering the occluded conformational states of glial human {gamma}-aminobutyric acid transporter subtypes, we found major semi-extended and minor ring-like conformations of zwitterionic {gamma}-aminobutyric acid in complex with Na{sup +} ion. The existence of the minor ring-like conformation of {gamma}-aminobutyric acid in complex with Na{sup +} ion may be attributed to the strengthening of the intramolecular H-bond by the electrostatic effect of Na{sup +} ion. Coupling substrate uptake into cells with the thermodynamically favorable Na{sup +} ion movement through substrate-Na{sup +} ion complex formation may be a mechanistic principle featuring transmembrane neurotransmitter-sodium symporter proteins.

  9. A gene duplication led to specialized gamma-aminobutyrate and beta-alanine aminotransferase in yeast

    DEFF Research Database (Denmark)

    Andersen, Gorm; Andersen, Birgit; Dobritzsch, D.

    2007-01-01

    In humans, beta-alanine (BAL) and the neurotransmitter gamma-aminobutyrate (GABA) are transaminated by a single aminotransferase enzyme. Apparently, yeast originally also had a single enzyme, but the corresponding gene was duplicated in the Saccharomyces kluyveri lineage. SkUGA1 encodes a homologue...

  10. Reduced gamma-aminobutyric acid concentration is associated with physical disability in progressive multiple sclerosis

    Science.gov (United States)

    Solanky, Bhavana S.; Muhlert, Nils; Tur, Carmen; Edden, Richard A. E.; Wheeler-Kingshott, Claudia A. M.; Miller, David H.; Thompson, Alan J.; Ciccarelli, Olga

    2015-01-01

    Neurodegeneration is thought to be the major cause of ongoing, irreversible disability in progressive stages of multiple sclerosis. Gamma-aminobutyric acid is the principle inhibitory neurotransmitter in the brain. The aims of this study were to investigate if gamma-aminobutyric acid levels (i) are abnormal in patients with secondary progressive multiple sclerosis compared with healthy controls; and (ii) correlate with physical and cognitive performance in this patient population. Thirty patients with secondary progressive multiple sclerosis and 17 healthy control subjects underwent single-voxel MEGA-PRESS (MEscher-GArwood Point RESolved Spectroscopy) magnetic resonance spectroscopy at 3 T, to quantify gamma-aminobutyric acid levels in the prefrontal cortex, right hippocampus and left sensorimotor cortex. All subjects were assessed clinically and underwent a cognitive assessment. Multiple linear regression models were used to compare differences in gamma-aminobutyric acid concentrations between patients and controls adjusting for age, gender and tissue fractions within each spectroscopic voxel. Regression was used to examine the relationships between the cognitive function and physical disability scores specific for these regions with gamma-aminobuytric acid levels, adjusting for age, gender, and total N-acetyl-aspartate and glutamine-glutamate complex levels. When compared with controls, patients performed significantly worse on all motor and sensory tests, and were cognitively impaired in processing speed and verbal memory. Patients had significantly lower gamma-aminobutyric acid levels in the hippocampus (adjusted difference = −0.403 mM, 95% confidence intervals −0.792, −0.014, P = 0.043) and sensorimotor cortex (adjusted difference = −0.385 mM, 95% confidence intervals −0.667, −0.104, P = 0.009) compared with controls. In patients, reduced motor function in the right upper and lower limb was associated with lower gamma-aminobutyric acid

  11. The gamma-aminobutyric acid shunt contributes to closing the tricarboxylic acid cycle in Synechocystis sp PCC 6803

    Energy Technology Data Exchange (ETDEWEB)

    Xiong, W; Brune, D; Vermaas, WFJ

    2014-07-16

    A traditional 2-oxoglutarate dehydrogenase complex is missing in the cyanobacterial tricarboxylic acid cycle. To determine pathways that convert 2-oxoglutarate into succinate in the cyanobacterium Synechocystis sp. PCC 6803, a series of mutant strains, Delta sll1981, Delta slr0370, Delta slr1022 and combinations thereof, deficient in 2-oxoglutarate decarboxylase (Sll1981), succinate semialdehyde dehydrogenase (Slr0370), and/or in gamma-aminobutyrate metabolism (Slr1022) were constructed. Like in Pseudomonas aeruginosa, N-acetylornithine aminotransferase, encoded by slr1022, was shown to also function as gamma-aminobutyrate aminotransferase, catalysing gamma-aminobutyrate conversion to succinic semialdehyde. As succinic semialdehyde dehydrogenase converts succinic semialdehyde to succinate, an intact gamma-aminobutyrate shunt is present in Synechocystis. The Delta sll1981 strain, lacking 2-oxoglutarate decarboxylase, exhibited a succinate level that was 60% of that in wild type. However, the succinate level in the Delta slr1022 and Delta slr0370 strains and the Delta sll1981/Delta slr1022 and Delta sll1981/Delta slr0370 double mutants was reduced to 20-40% of that in wild type, suggesting that the gamma-aminobutyrate shunt has a larger impact on metabolite flux to succinate than the pathway via 2-oxoglutarate decarboxylase. C-13-stable isotope analysis indicated that the gamma-aminobutyrate shunt catalysed conversion of glutamate to succinate. Independent of the 2-oxoglutarate decarboxylase bypass, the gamma-aminobutyrate shunt is a major contributor to flux from 2-oxoglutarate and glutamate to succinate in Synechocystis sp. PCC 6803.

  12. Mu Opioid Receptors in Gamma-Aminobutyric Acidergic Forebrain Neurons Moderate Motivation for Heroin and Palatable Food.

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    Charbogne, Pauline; Gardon, Olivier; Martín-García, Elena; Keyworth, Helen L; Matsui, Aya; Mechling, Anna E; Bienert, Thomas; Nasseef, Taufiq; Robé, Anne; Moquin, Luc; Darcq, Emmanuel; Ben Hamida, Sami; Robledo, Patricia; Matifas, Audrey; Befort, Katia; Gavériaux-Ruff, Claire; Harsan, Laura-Adela; von Elverfeldt, Dominik; Hennig, Jurgen; Gratton, Alain; Kitchen, Ian; Bailey, Alexis; Alvarez, Veronica A; Maldonado, Rafael; Kieffer, Brigitte L

    2017-05-01

    Mu opioid receptors (MORs) are central to pain control, drug reward, and addictive behaviors, but underlying circuit mechanisms have been poorly explored by genetic approaches. Here we investigate the contribution of MORs expressed in gamma-aminobutyric acidergic forebrain neurons to major biological effects of opiates, and also challenge the canonical disinhibition model of opiate reward. We used Dlx5/6-mediated recombination to create conditional Oprm1 mice in gamma-aminobutyric acidergic forebrain neurons. We characterized the genetic deletion by histology, electrophysiology, and microdialysis; probed neuronal activation by c-Fos immunohistochemistry and resting-state functional magnetic resonance imaging; and investigated main behavioral responses to opiates, including motivation to obtain heroin and palatable food. Mutant mice showed MOR transcript deletion mainly in the striatum. In the ventral tegmental area, local MOR activity was intact, and reduced activity was only observed at the level of striatonigral afferents. Heroin-induced neuronal activation was modified at both sites, and whole-brain functional networks were altered in live animals. Morphine analgesia was not altered, and neither was physical dependence to chronic morphine. In contrast, locomotor effects of heroin were abolished, and heroin-induced catalepsy was increased. Place preference to heroin was not modified, but remarkably, motivation to obtain heroin and palatable food was enhanced in operant self-administration procedures. Our study reveals dissociable MOR functions across mesocorticolimbic networks. Thus, beyond a well-established role in reward processing, operating at the level of local ventral tegmental area neurons, MORs also moderate motivation for appetitive stimuli within forebrain circuits that drive motivated behaviors. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  13. Synthesis of gamma-aminobutyric acid analogs based on carbohydrate scaffolds.

    Science.gov (United States)

    Zhong, Ming; Meng, Xiang-Bao; Li, Zhong-Jun

    2010-06-16

    Gamma-aminobutyric acid analogs based on sugar scaffolds were prepared in six to nine steps starting from D-glucal and D-galactal. The key step in the synthesis is the Vilsmeier-Haack reaction that affords the corresponding 2-C-formyl glycal on treatment with DMF and POCl(3). Oxidation of the aldehyde and reduction of the 4-azido group provided the corresponding GABA analog. Acylamide and tetrazole analogs were also prepared as the bioisosteres of the carboxylic acid. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

  14. Application of gamma-aminobutyric acid type A-benzodiazepine receptor imaging for study of neuropsychiatric disorders

    International Nuclear Information System (INIS)

    Bao Weiqi; Qiu Chun; Guan Yihui

    2012-01-01

    Gamma-aminobutyric acid type A-benzodiazepine receptors are heterogeneous polypeptide pentamers widely spread in the central nervous system on the neuron membrane. Different subunit combinations educe various neuro-inhibitory pharmacological effects such as sedative, hypnosis, anticonvulsion and anxiolysis. PET can be utilized to study the binding of the receptors in vivo. PET radioligands of gamma-aminobutyric acid type A-benzodiazepine receptors can be classified into 3 types: antagonists,agonists and reverse agonists, of which antagonist radiotracer 11 C-flumazenil is the most commonly applied in epilepsy, anxiety disorders, depression, vegetative state,addiction and other neuro-psychiatric disorders. (authors)

  15. Optimizing soaking and germination conditions to improve gamma-aminobutyric acid content in japonica and indica germinated brown rice

    NARCIS (Netherlands)

    Zhang, Q.; Xiang, J.; Zhang, L.; Zhu, X.; Evers, J.B.; Werf, van der W.; Duan, L.

    2014-01-01

    Germinated brown rice is a well-known functional food due to its high content of gamma-aminobutyric acid (GABA). This study was designed to test the difference of producing GABA in two domesticated rice genotypes (indica and japonica rice), and the effects of adding exogenous glutamic acid or

  16. Enrichment of Gamma-Aminobutyric Acid in Bean Sprouts: Exploring Biosynthesis of Plant Metabolite Using Common Household Reagents

    Science.gov (United States)

    Rojanarata, Theerasak; Plianwong, Samarwadee; Opanasopit, Praneet; Ngawhirunpat, Tanasait

    2018-01-01

    The enrichment of plant foods with gamma-aminobutyric acid (GABA) is currently an interesting issue in the field of nutraceuticals and can be used as an experiment for upper-division undergraduate students. Here, an interdisciplinary hands-on experiment to produce GABA-enriched mung bean sprouts using common household reagents is described. Based…

  17. Characterization of the gamma-aminobutyric acid receptor system in human brain gliomas

    International Nuclear Information System (INIS)

    Frattola, L.; Ferrarese, C.; Canal, N.; Gaini, S.M.; Galluso, R.; Piolti, R.; Trabucchi, M.

    1985-01-01

    The properties of [ 3 H]-gamma-aminobutyric acid [( 3 H]GABA) binding were studied in biopsied specimens from normal human brain and from 18 cases of human brain gliomas, made up of 6 astrocytomas, 6 glioblastomas, 3 oligodendrogliomas, and 3 medulloblastomas. In fresh membranes obtained from normal gray and white matter one population of Na+-dependent GABA receptors was observed, while in the frozen Triton X-100-treated membranes two distinct populations of Na+-independent binding sites were detected. Specific GABA binding sites in brain gliomas were shown only in frozen Triton X-100-treated membranes. As in normal tissue, these receptors are Na+-independent and bind [ 3 H]GABA with two distinct affinity components. The biochemical profiles of [ 3 H]GABA binding to membranes obtained from different tumors of glial origin are quite similar and cannot be related to the degree of malignancy of the neoplasia

  18. An Agrobacterium tumefaciens Strain with Gamma-Aminobutyric Acid Transaminase Activity Shows an Enhanced Genetic Transformation Ability in Plants

    OpenAIRE

    Nonaka, Satoko; Someya, Tatsuhiko; Zhou, Sha; Takayama, Mariko; Nakamura, Kouji; Ezura, Hiroshi

    2017-01-01

    Agrobacterium tumefaciens has the unique ability to mediate inter-kingdom DNA transfer, and for this reason, it has been utilized for plant genetic engineering. To increase the transformation frequency in plant genetic engineering, we focused on gamma-aminobutyric acid (GABA), which is a negative factor in the Agrobacterium-plant interaction. Recent studies have shown contradictory results regarding the effects of GABA on vir gene expression, leading to the speculation that GABA inhibits T-DN...

  19. Social and neural determinants of aggressive behavior: pharmacotherapeutic targets at serotonin, dopamine and gamma-aminobutyric acid systems.

    Science.gov (United States)

    Miczek, Klaus A; Fish, Eric W; De Bold, Joseph F; De Almeida, Rosa M M

    2002-10-01

    Aggressive outbursts that result in harm and injury present a major problem for the public health and criminal justice systems, but there are no adequate treatment options. Obstacles at the level of social policy, institutional regulation, and scientific strategy in developing animal models continue to impede the development of specific anti-aggressive agents for emergency and long-term treatments. To be more relevant to the clinical situation, preclinical aggression research has begun to focus on the neurobiological determinants of escalated aggressive behavior that exceeds species-typical patterns. It is the goal of this review to examine novel pharmacological and molecular tools that target the neural mechanisms for different kinds of aggressive behavior more selectively than previously possible and to outline potential pharmacotherapeutic options. (1) The preclinical focus on the behavioral characteristics and determinants of intense aggression promises to be most relevant to the clinical distinction between the proposed impulsive-reactive-hostile-affective subtypes of human aggression and the controlled-proactive-instrumental-predatory subtypes of aggression. The neural circuits for many types of human and animal aggression critically involve serotonin, dopamine and gamma-aminobutyric acid (GABA) and specific receptor subtypes. (2) The dynamic changes in frontal cortical serotonin that are triggered by engaging in aggressive behavior imply that serotonergic drug effects are largely determined by the functional state of the receptors at the time of drug treatment. Of the numerous 5-HT receptors currently identified, the 5-HT(1B) receptors offer a promising target for reducing impulsive aggressive behavior, particularly if the action can be limited to sites in the central nervous system. (3) Aggressive confrontations are salient stressors, both for the aggressor as well as the victim of aggression, that are accompanied by activation of the mesocorticolimbic but

  20. Mass fragmentographic determination of gamma-aminobutyric acid and glutamic acid in discrete amygdaloid nuclei of rat brain.

    Science.gov (United States)

    Nakamura, K; Matsumoto, T; Hirano, M; Kagoshima, H; Kuroki, T; Yao, H; Uchimura, H; Nakahara, T

    1987-06-01

    A mass fragmentographic method for the simultaneous quantification of gamma-aminobutyric acid (GABA) and glutamic acid is described. In a convenient one-step reaction, the two amino acids were derivatized with pentafluoropropionic anhydride and pentafluoropropanol. The derivatization products were stable for several days. The technique has been applied to the assay of GABA and Glu in five amygdaloid nuclei of the rat brain. The GABA level was high in the central and medial nuclei, whereas the Glu level was high in the lateral and basal nuclei. The regional distribution of GABA was different from that of Glu within the amygdaloid nuclei.

  1. Mass fragmentographic quantitation of glutamic acid and gamma-aminobutyric acid in cerebellar nuclei and sympathetic ganglia of rats.

    Science.gov (United States)

    Bertilsson, L; Costa, E

    1976-04-07

    A method for the simultaneous quantitation of glutamic acid and gamma-aminobutyric acid (GABA) in tissue by mass fragmentography has been developed. The amino and carboxylic groups of the two amino acids were in a convenient one-step reaction derivatized with pentafluoropropionic anhydride and hexafluoroisopropanol. Deuterium-labeled glutamic acid and GABA and a homologue of GABA have been used as internal standards. The usefulness of the technique has been demonstrated by measurements in parts of rat cerebellum and in the superior cervical ganglion.

  2. A fluorescence-coupled assay for gamma aminobutyric acid (GABA reveals metabolic stress-induced modulation of GABA content in neuroendocrine cancer.

    Directory of Open Access Journals (Sweden)

    Joseph E Ippolito

    Full Text Available Pathways involved in the synthesis of the neurotransmitter gamma-aminobutyric acid (GABA have been implicated in the pathogenesis of high grade neuroendocrine (NE neoplasms as well as neoplasms from a non-NE lineage. Using The Cancer Genome Atlas, overexpression of the GABA synthetic enzyme, glutamate decarboxylase 1 (GAD1, was found to be associated with decreased disease free-survival in prostate adenocarcinoma and decreased overall survival in clear cell renal cell carcinomas. Furthermore, GAD1 was found to be expressed in castrate-resistant prostate cancer cell lines, but not androgen-responsive cell lines. Using a novel fluorescence-coupled enzymatic microplate assay for GABA mediated through reduction of resazurin in a prostate neuroendocrine carcinoma (PNEC cell line, acid microenvironment-induced stress increased GABA levels while alkaline microenvironment-induced stress decreased GABA through modulation of GAD1 and glutamine synthetase (GLUL activities. Moreover, glutamine but not glucose deprivation decreased GABA through modulation of GLUL. Consistent with evidence in prokaryotic and eukaryotic organisms that GABA synthesis mediated through GAD1 may play a crucial role in surviving stress, GABA may be an important mediator of stress survival in neoplasms. These findings identify GABA synthesis and metabolism as a potentially important pathway for regulating cancer cell stress response as well as a potential target for therapeutic strategies.

  3. Inhibition of microbial growth and enrichment of gamma-aminobutyric acid during germination of brown rice by electrolyzed oxidizing water.

    Science.gov (United States)

    Lu, Zhan-Hui; Zhang, Yan; Li, Li-Te; Curtis, Rempel B; Kong, Xiao-Lin; Fulcher, R Gary; Zhang, Gong; Cao, Wei

    2010-03-01

    Electrolyzed oxidizing water (EOW) has been regarded as a potential environmentally friendly broad spectrum microbial decontaminant. EOW with a pH of 3.0 and oxidation reduction potential of 1,079.0 mV were generated by the electrolysis of a dilute NaCl solution (20 mM) in an electrochemical cell. The effects of EOW, 1% NaClO solution, and alkaline electrolyzed water on controlling microbial growth, germination ratio, and enrichment of gamma-aminobutyric acid in germinated brown rice (GBR) were evaluated in this study. Results show that EOW was the most effective at inhibiting microbial growth during germination. Rinsing the rice grains with EOW at 12-h intervals resulted in aerobic plate count reductions of 4.82 log CFU/g, while soaking resulted in bacterial count reductions of 5.38 log CFU/g after 72 h of germination. Moreover, EOW significantly enriched gamma-aminobutyric acid content in GBR (P < 0.05); content was increased 1.6 times in grain rinsed with EOW and 1.8 times in grain soaked in EOW. The findings indicate that EOW is a feasible disinfectant for industrial GBR production.

  4. Effects of inhibitors of protein synthesis and intracellular transport on the gamma-aminobutyric acid agonist-induced functional differentiation of cultured cerebellar granule cells

    DEFF Research Database (Denmark)

    Belhage, B; Hansen, Gert Helge; Meier, E

    1990-01-01

    The effect of inhibitors of protein synthesis (actinomycin D, cycloheximide), proteases (leupeptin), and intracellular transport (colchicine, monensin) on the gamma-aminobutyric acid (GABA) agonist [4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP)]-induced changes in morphological differenti......The effect of inhibitors of protein synthesis (actinomycin D, cycloheximide), proteases (leupeptin), and intracellular transport (colchicine, monensin) on the gamma-aminobutyric acid (GABA) agonist [4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP)]-induced changes in morphological...

  5. Hypergravity exposure decreases gamma-aminobutyric acid immunoreactivity in axon terminals contacting pyramidal cells in the rat somatosensory cortex: a quantitative immunocytochemical image analysis

    Science.gov (United States)

    D'Amelio, F.; Wu, L. C.; Fox, R. A.; Daunton, N. G.; Corcoran, M. L.; Polyakov, I.

    1998-01-01

    Quantitative evaluation of gamma-aminobutyric acid immunoreactivity (GABA-IR) in the hindlimb representation of the rat somatosensory cortex after 14 days of exposure to hypergravity (hyper-G) was conducted by using computer-assisted image processing. The area of GABA-IR axosomatic terminals apposed to pyramidal cells of cortical layer V was reduced in rats exposed to hyper-G compared with control rats, which were exposed either to rotation alone or to vivarium conditions. Based on previous immunocytochemical and behavioral studies, we suggest that this reduction is due to changes in sensory feedback information from muscle receptors. Consequently, priorities for muscle recruitment are altered at the cortical level, and a new pattern of muscle activity is thus generated. It is proposed that the reduction observed in GABA-IR of the terminal area around pyramidal neurons is the immunocytochemical expression of changes in the activity of GABAergic cells that participate in reprogramming motor outputs to achieve effective movement control in response to alterations in the afferent information.

  6. Effects of single and combined administration of fermented barley extract and gamma-aminobutyric acid on the development of atopic dermatitis in NC/Nga mice.

    Science.gov (United States)

    Hokazono, Hideki; Omori, Toshiro; Ono, Kazuhisa

    2010-01-01

    We examined the effects single and combined administration of fermented barley extract P (FBEP), prepared from barley-shochu distillery by-products, and gamma-aminobutyric acid (GABA) on the development of atopic dermatitis (AD)-like skin lesions in NC/Nga mice. Single administration of FBEP and GABA dose-dependently reduced the development of AD-like skin lesions in mice. GABA reduced the development of AD-like skin lesions by suppressing serum immunoglobulin E (IgE) and splenocyte interleukin (IL)-4 production, while FBEP reduced skin lesions without affecting the IgE or cytokine production. However, in mice with induced AD-like skin lesions, combined administration of FBEP and GABA decreased serum IgE levels and splenic cell IL-4 production, and increased splenic cell interferon-gamma production. These results suggest that combined administration of FBEP and GABA alleviated AD-like skin lesions in the NC/Nga mice by adjusting the Th1/Th2 balance to a Th1-predominant immune response.

  7. A case of relapsing encephalitis positive for gamma aminobutyric acid (GABA)A receptor antibody associated with Type B3 thymoma.

    Science.gov (United States)

    Kitano, Takaya; Kinoshita, Makoto; Shimazu, Kohki; Fushimi, Hiroaki; Omori, Kenichi; Hazama, Takanori

    2016-11-29

    A 87-year-old female presented with subacute progression of cognitive decline. Fluid-attenuated inversion recovery images of brain MRI showed multifocal high-intensity lesions. Thoracic CT image revealed the presence of thymoma, and serum autoantibody screening showed positivity for anti-gamma aminobutyric acid (GABA) A receptor antibody. Histopathological analysis confirmed type B3 thymoma after thymectomy. The patient received both plasmapheresis and intravenous methylprednisolone therapy, and showed remarkable amelioration of clinical symptoms and MRI abnormal high intensity. However, after 2 month from the clinical recovery, the patient showed recurrence of brain lesions and intravenous methylprednisolone monotherapy was performed. Continuation of oral steroid therapy was required to maintain the quienscent state of inflammation within the central nervous system. Anti-GABA A receptor antibody is a recently discovered novel autoantibody associated with autoimmue encephalitis. Due to the limited number of literature reported, clinical course and therapeutic response of GABA A receptor antibody encephalitis remains elusive. Here we reported a rare case of GABA A receptor antibody encephalitis with type B3 thymoma. Clinical, radiological and therapeutic courses described in our report highlight the importance of immunotherapy for treatment of the disease.

  8. Conformational basis for the Li(+)-induced leak current in the rat gamma-aminobutyric acid (GABA) transporter-1

    DEFF Research Database (Denmark)

    MacAulay, Nanna; Zeuthen, Thomas; Gether, Ulrik

    2002-01-01

    The rat gamma-aminobutyric acid transporter-1 (GAT-1) was expressed in Xenopus laevis oocytes and the substrate-independent Li(+)-induced leak current was examined using two-electrode voltage clamp. The leak current was not affected by the addition of GABA and was not due to H(+) permeation. The Li......(+)-bound conformation of the protein displayed a lower passive water permeability than that of the Na(+)- and choline (Ch(+))-bound conformations and the leak current did not saturate with increasing amounts of Li(+) in the test solution. The mechanism that gives rise to the leak current did not support active water...... millimolar concentrations of Na(+) (the apparent affinity constant, K'(0.5) = 3 mM). In addition, it was found that the GABA transport current was sustained at correspondingly low Na(+) concentrations if Li(+) was present instead of choline. This is consistent with a model in which Li(+) can bind...

  9. Effects of glutamate decarboxylase and gamma-aminobutyric acid (GABA) transporter on the bioconversion of GABA in engineered Escherichia coli.

    Science.gov (United States)

    Le Vo, Tam Dinh; Kim, Tae Wan; Hong, Soon Ho

    2012-05-01

    Gamma-aminobutyric acid (GABA) is a non-essential amino acid and a precursor of pyrrolidone, a monomer of nylon 4. GABA can be biosynthesized through the decarboxylation of L: -glutamate by glutamate decarboxylase. In this study, the effects of glutamate decarboxylase (gadA, gadB), glutamate/GABA antiporter (gadC) and GABA aminotransferase (gabT) on GABA production were investigated in Escherichia coli. Glutamate decarboxylase was overexpressed alone or with the glutamate/GABA antiporter to enhance GABA synthesis. GABA aminotransferase, which redirects GABA into the TCA cycle, was knock-out mutated. When gadB and gadC were co-overexpressed in the gabT mutant strain, a final GABA concentration of 5.46 g/l was obtained from 10 g/l of monosodium glutamate (MSG), which corresponded to a GABA yield of 89.5%.

  10. Cortical gamma-aminobutyric acid and glutamate in posttraumatic stress disorder and their relationships to self-reported sleep quality.

    Science.gov (United States)

    Meyerhoff, Dieter J; Mon, Anderson; Metzler, Thomas; Neylan, Thomas C

    2014-05-01

    To test if posttraumatic stress disorder (PTSD) is associated with low brain gamma-aminobutyric acid (GABA) levels and if reduced GABA is mediated by poor sleep quality. Laboratory study using in vivo proton magnetic resonance spectroscopy (1H MRS) and behavioral testing. VA Medical Center Research Service, Psychiatry and Radiology. Twenty-seven patients with PTSD (PTSD+) and 18 trauma-exposed controls without PTSD (PTSD-), recruited from United States Army reservists, Army National Guard, and mental health clinics. None. 1H MRS at 4 Tesla yielded spectra from three cortical brain regions. In parieto-occipital and temporal cortices, PTSD+ had lower GABA concentrations than PTSD-. As expected, PTSD+ had higher depressive and anxiety symptom scores and a higher Insomnia Severity Index (ISI) score. Higher ISI correlated with lower GABA and higher glutamate levels in parieto-occipital cortex and tended to correlate with lower GABA in the anterior cingulate. The relationship between parieto-occipital GABA and PTSD diagnosis was fully mediated through insomnia severity. Lower N-acetylaspartate and glutamate concentrations in the anterior cingulate cortex correlated with higher arousal scores, whereas depressive and anxiety symptoms did generally not influence metabolite concentrations. Low brain gamma-aminobutyric acid (GABA) concentration in posttraumatic stress disorder (PTSD) is consistent with most findings in panic and social anxiety disorders. Low GABA associated with poor sleep quality is consistent with the hyperarousal theory of both primary insomnia and PTSD. Our data demonstrate that poor sleep quality mediates low parieto-occipital GABA in PTSD. The findings have implications for PTSD treatment approaches.

  11. Severe Intellectual Disability and Enhanced Gamma-Aminobutyric Acidergic Synaptogenesis in a Novel Model of Rare RASopathies.

    Science.gov (United States)

    Papale, Alessandro; d'Isa, Raffaele; Menna, Elisabetta; Cerovic, Milica; Solari, Nicola; Hardingham, Neil; Cambiaghi, Marco; Cursi, Marco; Barbacid, Mariano; Leocani, Letizia; Fasano, Stefania; Matteoli, Michela; Brambilla, Riccardo

    2017-02-01

    Dysregulation of Ras-extracellular signal-related kinase (ERK) signaling gives rise to RASopathies, a class of neurodevelopmental syndromes associated with intellectual disability. Recently, much attention has been directed at models bearing mild forms of RASopathies whose behavioral impairments can be attenuated by inhibiting the Ras-ERK cascade in the adult. Little is known about the brain mechanisms in severe forms of these disorders. We performed an extensive characterization of a new brain-specific model of severe forms of RASopathies, the KRAS 12V mutant mouse. The KRAS 12V mutation results in a severe form of intellectual disability, which parallels mental deficits found in patients bearing mutations in this gene. KRAS 12V mice show a severe impairment of both short- and long-term memory in a number of behavioral tasks. At the cellular level, an upregulation of ERK signaling during early phases of postnatal development, but not in the adult state, results in a selective enhancement of synaptogenesis in gamma-aminobutyric acidergic interneurons. The enhancement of ERK activity in interneurons at this critical postnatal time leads to a permanent increase in the inhibitory tone throughout the brain, manifesting in reduced synaptic transmission and long-term plasticity in the hippocampus. In the adult, the behavioral and electrophysiological phenotypes in KRAS 12V mice can be temporarily reverted by inhibiting gamma-aminobutyric acid signaling but not by a Ras-ERK blockade. Importantly, the synaptogenesis phenotype can be rescued by a treatment at the developmental stage with Ras-ERK inhibitors. These data demonstrate a novel mechanism underlying inhibitory synaptogenesis and provide new insights in understanding mental dysfunctions associated to RASopathies. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  12. Nicotine stimulates pancreatic cancer xenografts by systemic increase in stress neurotransmitters and suppression of the inhibitory neurotransmitter gamma-aminobutyric acid.

    Science.gov (United States)

    Al-Wadei, Hussein A N; Plummer, Howard K; Schuller, Hildegard M

    2009-03-01

    Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer mortality in Western countries. We have shown previously that four representative human PDAC cell lines were regulated by beta-adrenoreceptors via cyclic adenosine 3',5'-monophosphate (cAMP)-dependent signaling. In the current study, we have tested the hypothesis that nicotine stimulates the growth of PDAC xenografts in nude mice by increasing the systemic levels of the stress neurotransmitters adrenaline and noradrenaline, which are the physiological agonists for beta-adrenoreceptors and that inhibition by gamma-aminobutyric acid (GABA) of the adenylyl cyclase-dependent pathway downstream of adrenoreceptors blocks this effect. The size of xenografts from PDAC cell line Panc-1 was determined 30 days after inoculation of the cancer cells. Stress neurotransmitters in serum as well as cAMP in the cellular fraction of blood and in tumor tissue were assessed by immunoassays. Levels of GABA, its synthesizing enzymes GAD65 and GAD67 and beta-adrenergic signaling proteins in the tumor tissue were determined by western blotting. Nicotine significantly increased the systemic levels of adrenaline, noradrenaline and cAMP while increasing xenograft size and protein levels of cAMP, cyclic AMP response element-binding protein and p-extracellular signal-regulated kinase 1/2 in the tumor tissue. Nicotine additionally reduced the protein levels of both GAD isozymes and GABA in tumor tissue. Treatment with GABA abolished these responses to nicotine and blocked the development of xenografts in mice not exposed to nicotine. These findings suggest that the development and progression of PDAC is subject to significant modulation by stimulatory stress neurotransmitters and inhibitory GABA and that treatment with GABA may be useful for marker-guided cancer intervention of PDAC.

  13. Phenotypic consequences of deletion of the {gamma}{sub 3}, {alpha}{sub 5}, or {beta}{sub 3} subunit of the type A {gamma}-aminobutyric acid receptor in mice

    Energy Technology Data Exchange (ETDEWEB)

    Culia, C.T.; Stubbs, L.J.; Montgomery, C.S.; Russell, L.B.; Rinchik, E.M. [Oak Ridge National Lab., TN (United States)

    1994-03-29

    Three genes (Gabrg3, Gabra5, and Gabrb3) encoding the {gamma}{sub 3}, {alpha}{sub 5}, and {beta}{sub 3} subunits of the type A {gamma}-aminobutyric acid receptor, respectively, are known to map near the pink-eyed dilution (p) locus in mouse chromosome 7. This region shares homology with a segment of human chromosome 15 that is implicated in Angelman syndrome, an inherited neurobehavioral disorder. By mapping Gabrg3-Gabra5-Gabrb3-telomere. Like Gabrb3, neither the Gabra5 nor Gabrg3 gene is functionally imprinted in adult mouse brain. Mice deleted for all three subunits die at birth with a cleft palate, although there are rare survivors ({approximately} 5%) that do not have a cleft palate but do exhibit a neurological abnormality characterized by tremor, jerky gait, and runtiness. The authors have previously suggested that deficiency of the {beta}{sub 3} subunit may be responsible for the clefting defect. Most notably, however, in this report they describe mice carrying two overlapping, complementing p deletions that fail to express the {gamma}{sub 3} transcript, as well as mice from another line that express neither the {gamma}{sub 3} nor {alpha}{sub 5} transcripts. Surprisingly, mice from both of these lines are phenotypically normal and do not exhibit any of the neurological symptoms characteristic of the rare survivors that are deleted for all three ({gamma}{sub 3}, {alpha}{sub 5}, and {beta}{sub 3}) subunits. These mice therefore provide a whole-organism type A {gamma}-aminobutyric-acid receptor background that is devoid of any receptor subtypes that normally contain the {gamma}{sub 3} and/or {alpha}{sub 5} subunits. The absence of an overt neurological phenotype in mice lacking the {gamma}{sub 3} and/or {alpha}{sub 5} subunits also suggests that mutations in these genes are unlikely to provide useful animal models for Angelman syndrome in humans.

  14. Enhanced Production of Gamma-Aminobutyric Acid by Optimizing Culture Conditions of Lactobacillus brevis HYE1 Isolated from Kimchi, a Korean Fermented Food.

    Science.gov (United States)

    Lim, Hee Seon; Cha, In-Tae; Roh, Seong Woon; Shin, Hae-Hun; Seo, Myung-Ji

    2017-03-28

    This study evaluated the effects of culture conditions, including carbon and nitrogen sources, L-monosodium glutamate (MSG), and initial pH, on gamma-aminobutyric acid (GABA) production by Lactobacillus brevis HYE1 isolated from kimchi, a Korean traditional fermented food. L. brevis HYE1 was screened by the production analysis of GABA and genetic analysis of the glutamate decarboxylase gene, resulting in 14.64 mM GABA after 48 h of cultivation in MRS medium containing 1% (w/v) MSG. In order to increase GABA production by L. brevis HYE1, the effects of carbon and nitrogen sources on GABA production were preliminarily investigated via one-factor-at-a-time optimization strategy. As the results, 2% maltose and 3% tryptone were determined to produce 17.93 mM GABA in modified MRS medium with 1% (w/v) MSG. In addition, the optimal MSG concentration and initial pH were determined to be 1% and 5.0, respectively, resulting in production of 18.97 mM GABA. Thereafter, response surface methodology (RSM) was applied to determine the optimal conditions of the above four factors. The results indicate that pH was the most significant factor for GABA production. The optimal culture conditions for maximum GABA production were also determined to be 2.14% (w/v) maltose, 4.01% (w/v) tryptone, 2.38% (w/v) MSG, and an initial pH of 4.74. In these conditions, GABA production by L. brevis HYE1 was predicted to be 21.44 mM using the RSM model. The experiment was performed under these optimized conditions, resulting in GABA production of 18.76 mM. These results show that the predicted and experimental values of GABA production are in good agreement.

  15. Increased Cortical Gamma-Aminobutyric Acid Precedes Incomplete Extinction of Conditioned Fear and Increased Hippocampal Excitatory Tone in a Mouse Model of Mild Traumatic Brain Injury.

    Science.gov (United States)

    Schneider, Brandy L; Ghoddoussi, Farhad; Charlton, Jennifer L; Kohler, Robert J; Galloway, Matthew P; Perrine, Shane A; Conti, Alana C

    2016-09-01

    Mild traumatic brain injury (mTBI) contributes to development of affective disorders, including post-traumatic stress disorder (PTSD). Psychiatric symptoms typically emerge in a tardive fashion post-TBI, with negative effects on recovery. Patients with PTSD, as well as rodent models of PTSD, demonstrate structural and functional changes in brain regions mediating fear learning, including prefrontal cortex (PFC), amygdala (AMYG), and hippocampus (HC). These changes may reflect loss of top-down control by which PFC normally exhibits inhibitory influence over AMYG reactivity to fearful stimuli, with HC contribution. Considering the susceptibility of these regions to injury, we examined fear conditioning (FC) in the delayed post-injury period, using a mouse model of mTBI. Mice with mTBI displayed enhanced acquisition and delayed extinction of FC. Using proton magnetic resonance spectroscopy ex vivo, we examined PFC, AMYG, and HC levels of gamma-aminobutyric acid (GABA) and glutamate as surrogate measures of inhibitory and excitatory neurotransmission, respectively. Eight days post-injury, GABA was increased in PFC, with no significant changes in AMYG. In animals receiving FC and mTBI, glutamate trended toward an increase and the GABA/glutamate ratio decreased in ventral HC at 25 days post-injury, whereas GABA decreased and GABA/glutamate decreased in dorsal HC. These neurochemical changes are consistent with early TBI-induced PFC hypoactivation facilitating the fear learning circuit and exacerbating behavioral fear responses. The latent emergence of overall increased excitatory tone in the HC, despite distinct plasticity in dorsal and ventral HC fields, may be associated with disordered memory function, manifested as incomplete extinction and enhanced FC recall.

  16. The Intracellular Loops of the GB2 Subunit Are Crucial for G-Protein Coupling of the Heteromeric Gamma-Aminobutyrate B Receptor

    Czech Academy of Sciences Publication Activity Database

    Havlíčková, Michaela; Prezeau, L.; Duthey, B.; Bettler, B.; Pin, J. P.; Blahoš, Jaroslav

    2002-01-01

    Roč. 62, č. 2 (2002), s. 343-350 ISSN 0026-895X R&D Projects: GA ČR GA301/00/0654; GA MZd NL6114; GA MZd NF6704 Institutional research plan: CEZ:AV0Z5008914 Keywords : GABA * Gamma-aminobutyrate * GPCR Subject RIV: FR - Pharmacology ; Medidal Chemistry Impact factor: 5.480, year: 2002

  17. An Agrobacterium tumefaciens Strain with Gamma-Aminobutyric Acid Transaminase Activity Shows an Enhanced Genetic Transformation Ability in Plants

    Science.gov (United States)

    Nonaka, Satoko; Someya, Tatsuhiko; Zhou, Sha; Takayama, Mariko; Nakamura, Kouji; Ezura, Hiroshi

    2017-01-01

    Agrobacterium tumefaciens has the unique ability to mediate inter-kingdom DNA transfer, and for this reason, it has been utilized for plant genetic engineering. To increase the transformation frequency in plant genetic engineering, we focused on gamma-aminobutyric acid (GABA), which is a negative factor in the Agrobacterium-plant interaction. Recent studies have shown contradictory results regarding the effects of GABA on vir gene expression, leading to the speculation that GABA inhibits T-DNA transfer. In this study, we examined the effect of GABA on T-DNA transfer using a tomato line with a low GABA content. Compared with the control, the T-DNA transfer frequency was increased in the low-GABA tomato line, indicating that GABA inhibits T-DNA transfer. Therefore, we bred a new A. tumefaciens strain with GABA transaminase activity and the ability to degrade GABA. The A. tumefaciens strain exhibited increased T-DNA transfer in two tomato cultivars and Erianthus arundinacues and an increased frequency of stable transformation in tomato. PMID:28220841

  18. Spectroscopic investigation on structure and pH dependent Cocrystal formation between gamma-aminobutyric acid and benzoic acid

    Science.gov (United States)

    Du, Yong; Xue, Jiadan; Cai, Qiang; Zhang, Qi

    2018-02-01

    Vibrational spectroscopic methods, including terahertz absorption and Raman scattering spectroscopy, were utilized for the characterization and analysis of gamma-aminobutyric acid (GABA), benzoic acid (BA), and the corresponding GABA-BA cocrystal formation under various pH values of aqueous solution. Vibrational spectroscopic results demonstrated that the solvent GABA-BA cocrystal, similar as grinding counterpart, possessed unique characteristic features compared with that of starting parent compounds. The change of vibrational modes for GABA-BA cocrystal comparing with starting components indicates there is strong inter-molecular interaction between GABA and BA molecules during its cocrystallization process. Formation of GABA-BA cocrystal under slow solvent evaporation is impacted by the pH value of aqueous solution. Vibrational spectra indicate that the GABA-BA cocrystal could be stably formed with the solvent condition of 2.00 ≤ pH ≤ 7.00. In contrast, such cocrystallization did not occur and the cocrystal would dissociate into its parent components when the pH value of solvent is lower than 2.00. This study provides experimental benchmark to discriminate and identify the structure of cocrystal and also pH-dependent cocrystallization effect with vibrational spectroscopic techniques in solid-state pharmaceutical fields.

  19. Identification of rare noncoding sequence variants in gamma-aminobutyric acid A receptor, alpha 4 subunit in autism spectrum disorder.

    Science.gov (United States)

    Griswold, Anthony J; Van Booven, Derek; Cuccaro, Michael L; Haines, Jonathan L; Gilbert, John R; Pericak-Vance, Margaret A

    2018-01-01

    Alterations of the gamma-aminobutyric acid (GABA) signaling system has been strongly linked to the pathophysiology of autism spectrum disorder (ASD). Genetic associations of common variants in GABA receptor subunits, in particular GABRA4 on chromosome 4p12, with ASD have been replicated by several studies. Moreover, molecular investigations have identified altered transcriptional and translational levels of this gene and protein in brains of ASD individuals. Since the genotyped common variants are likely not the functional variants contributing to the molecular consequences or underlying ASD phenotype, this study aims to examine rare sequence variants in GABRA4, including those outside the protein coding regions of the gene. We comprehensively re-sequenced the entire protein coding and noncoding portions of the gene and putative regulatory sequences in 82 ASD individuals and 55 developmentally typical pediatric controls, all homozygous for the most significant previously associated ASD risk allele (G/G at rs1912960). We identified only a single common, coding variant, and no association of any single marker or set of variants with ASD. Functional annotation of noncoding variants identified several rare variants in putative regulatory sites. Finally, a rare variant unique to ASD cases, in an evolutionary conserved site of the 3'UTR, shows a trend toward decreasing gene expression. Hence, GABRA4 rare variants in noncoding DNA may be variants of modest physiological effects in ASD etiology.

  20. Uncertainty assessment of gamma-aminobutyric acid concentration of different brain regions in individual and group using residual bootstrap analysis.

    Science.gov (United States)

    Chen, Meng; Liao, Congyu; Chen, Song; Ding, Qiuping; Zhu, Darong; Liu, Hui; Yan, Xu; Zhong, Jianhui

    2017-06-01

    The aim of this work is to quantify individual and regional differences in the relative concentration of gamma-aminobutyric acid (GABA) in human brain with in vivo magnetic resonance spectroscopy. Spectral editing Mescher-Garwood point resolved spectroscopy (MEGA-PRESS) sequence and GABA analysis toolkit (Gannet) were used to detect and quantify GABA in anterior cingulate cortex (ACC) and occipital cortex (OCC) of healthy volunteers. Residual bootstrap, a model-based statistical analysis technique, was applied to resample the fitting residuals of GABA from the Gaussian fitting model (referred to as GABA + thereafter) in both individual and group data of ACC and OCC. The inter-subject coefficient of variation (CV) of GABA + in OCC (20.66 %) and ACC (12.55 %) with residual bootstrap was lower than that of a standard Gaussian model analysis (21.58 % and 16.73 % for OCC and ACC, respectively). The intra-subject uncertainty and CV of OCC were lower than that of ACC in both analyses. The residual bootstrap analysis thus provides a more robust uncertainty estimation of individual and group GABA + detection in different brain regions, which may be useful in our understanding of GABA biochemistry in brain and its use for the diagnosis of related neuropsychiatric diseases.

  1. Dynamic changes in gamma-aminobutyric acid and glutamate decarboxylase activity in oats (Avena nuda L.) during steeping and germination.

    Science.gov (United States)

    Xu, Jian Guo; Hu, Qing Ping; Duan, Jiang Lian; Tian, Cheng Rui

    2010-09-08

    Gamma-aminobutyric acid (GABA) is the principal inhibitory neurotransmitter in the central nervous system and provides beneficial effects for human and other animals health. To accumulate GABA, samples from two different naked oat cultivars, Baiyan II and Bayou I, were steeped and germinated in an incubator. The content of GABA and glutamic acid as well as the activity of the glutamate decarboxylase (GAD) in oats during steeping and germination were investigated with an amino acid automatic analyzer. Compared with raw groats, an increase in GABA content of oat groats during steeping and germination was continuously observed for two oat cultivars. The activity of GAD increased greatly at the end of steeping and the second stage of germination for Baiyan II and Bayou I, respectively. Glutamic acid content of treated oat groats was significantly lower than that in raw groats until the later period of germination. GABA was correlated (p<0.01) significantly and positively with the glutamic acid rather than GAD activity in the current study. The results indicates that steeping and germination process under highly controlled conditions can effectively accumulate the GABA in oat groats for Baiyan II and Bayou I, which would greatly facilitate production of nutraceuticals or food ingredients that enable consumers to gain greater access to the health benefits of oats. However, more assays need to be further performed with more oat cultivars.

  2. Analysis of subcomponents of the gamma-aminobutyric acid/benzodiazepine receptor macromolecular complex in mammalian central nervous system

    International Nuclear Information System (INIS)

    McCabe, R.T.

    1987-01-01

    Since the presence of endogenous gamma-aminobutyric acid (GABA) may affect benzodiazepine binding to tissue sections in autoradiographic studies, a protocol designed to check for this influence has been investigated. [ 3 H]Flunitrazepam (1 nM) was used to label benzodiazepine receptors for autoradiographic localization. Bicuculline was added to the incubation medium of an additional set of tissue sections to antagonize any potential effect of endogenous GABA. Binding in these sections was compared to that occurring in another set in which excess GABA was added to create further GABA enhancement. Binding was also compared to adjacent sections which were treated similarly but also preincubated in distilled-deionized water to burst the cells by osmotic shock and eliminate endogenous GABA, thereby preventing any effect on benzodiazepine binding. The results indicated that endogenous GABA is indeed present in the slide-mounted tissue sections and is affecting benzodiazepine receptor binding differentially in various regions of the brain depending on the density of GABAergic innervation. Scatchard analysis of saturation data demonstrated that the alteration in BZ binding due to GABA was a result of a change in the affinity rather than number of receptors present

  3. An Agrobacterium tumefaciens Strain with Gamma-Aminobutyric Acid Transaminase Activity Shows an Enhanced Genetic Transformation Ability in Plants.

    Science.gov (United States)

    Nonaka, Satoko; Someya, Tatsuhiko; Zhou, Sha; Takayama, Mariko; Nakamura, Kouji; Ezura, Hiroshi

    2017-02-21

    Agrobacterium tumefaciens has the unique ability to mediate inter-kingdom DNA transfer, and for this reason, it has been utilized for plant genetic engineering. To increase the transformation frequency in plant genetic engineering, we focused on gamma-aminobutyric acid (GABA), which is a negative factor in the Agrobacterium-plant interaction. Recent studies have shown contradictory results regarding the effects of GABA on vir gene expression, leading to the speculation that GABA inhibits T-DNA transfer. In this study, we examined the effect of GABA on T-DNA transfer using a tomato line with a low GABA content. Compared with the control, the T-DNA transfer frequency was increased in the low-GABA tomato line, indicating that GABA inhibits T-DNA transfer. Therefore, we bred a new A. tumefaciens strain with GABA transaminase activity and the ability to degrade GABA. The A. tumefaciens strain exhibited increased T-DNA transfer in two tomato cultivars and Erianthus arundinacues and an increased frequency of stable transformation in tomato.

  4. Enhancing gamma-aminobutyric acid content in germinated brown rice by repeated treatment of soaking and incubation.

    Science.gov (United States)

    Thitinunsomboon, Somboon; Keeratipibul, Suwimon; Boonsiriwit, Athip

    2013-02-01

    Gamma-aminobutyric acid (GABA), commonly produced by germination of brown rice grain, is a free amino acid which could help relieving or preventing non-communicable diseases in human. Several research works have been conducted on GABA production from germinated brown rice. However, the yielded GABA (10.1-69.2 mg/100 g germinated brown rice) was comparatively low; thus the amount was insufficient to be used as active ingredients in functional foods. The objective of this study was to explore alternative methods in order to gain higher yield of GABA. A new process of repeated soaking (in tap water at 35 °C, 3 h) and incubation (at 37 °C, 21 h) during germination was developed. The amount of GABA produced was highest at 116.88 ± 9.24 mg/100 g germinated brown rice (dry basis). However, an unpleasant odour was generated by some microorganisms during long germination. Lactic acid was applied at soaking step to overcome this problem; whereby 0.5% lactic acid solution (vol./vol.) could effectively control the microorganisms without impairing GABA producing ability and sensory qualities.

  5. [Effect of gamma-aminobutyric acid-rich germinated brown rice on indexes of life-style related diseases].

    Science.gov (United States)

    Morita, Hiroyuki; Uno, Yoshihiro; Umemoto, Takao; Sugiyama, Chiyo; Matsumoto, Masami; Wada, Yuji; Ishizuka, Tatsuo

    2004-03-01

    We examined the effects of gamma-aminobutyric acid-rich germinated brown rice (germinated brown rice) on principal indexes of life-style related diseases in 67 volunteers aged 71 +/- 8. They were divided into two groups; germinated brown rice group, which had an equal amount of the germinated brown rice to polished rice for 11 to 13 months, and control group, which had polished rice alone for the same period. Differences of indexes before and after the examination between the two groups were compared. Significant increases in body fat ratio, hemoglobin A1c and mean red cell volume and a significant decrease in mean red cell hemoglobin concentration were observed in the germinated brown rice group. However, there was no difference of changes in body mass index, blood pressure, serum lipid, hepatic and renal functions, bone metabolic markers, bone density, depression score, red blood cell counts, hemoglobin, hematocrit, and homeostasis model assessment of insulin resistance between the two groups. These findings suggested that germinated brown rice might not improve glucose metabolism.

  6. Decreased Hepatocyte Growth Factor (HGF) and Gamma Aminobutyric Acid (GABA) in Individuals with Obsessive-Compulsive Disorder (OCD).

    Science.gov (United States)

    Russo, Anthony J; Pietsch, Stefanie C

    2013-01-01

    There is support for the role of gamma aminobutyric acid (GABA) in the etiology of mood disorders. Recent research has shown that hepatocyte growth factor (HGF) modulates GABAergic inhibition and seizure susceptibility. This study was designed to determine and correlate plasma levels of HGF and GABA as well as symptom severity in individuals with obsessive-compulsive disorder (OCD). Plasma from 15 individuals with OCD (9 males, 6 females;, mean age 38.7 years) and 17 neurotypical controls (10 males, 7 females; mean age 35.2 years) was assessed for HGF, GABA, urokinase plasminogen activator (uPA), and urokinase plasminogen activator receptor (uPAR) concentration using enzyme-linked immunosorbest assays ELISAs. Symptom severity was assessed in these OCD individuals and compared with HGF and GABA concentrations. In this preliminary study, individuals with OCD had significantly decreased HGF levels, decreased plasma levels of GABA and decreased uPA. We found that both uPA and uPAR levels correlate with HGF. Both low uPA and low uPAR levels correlate with high symptom severity in individuals with OCD. Low GABA levels in OCD individuals also correlate with high symptom severity. These results demonstrate a preliminary association between HGF, GABA, uPA levels, and OCD and suggest that plasma GABA and uPA levels are related to symptom severity in individuals with OCD.

  7. Gamma-aminobutyric acid receptor genes and nicotine dependence: evidence for association from a case-control study.

    Science.gov (United States)

    Agrawal, Arpana; Pergadia, Michele L; Saccone, Scott F; Hinrichs, Anthony L; Lessov-Schlaggar, Christina N; Saccone, Nancy L; Neuman, Rosalind J; Breslau, Naomi; Johnson, Eric; Hatsukami, Dorothy; Montgomery, Grant W; Heath, Andrew C; Martin, Nicholas G; Goate, Alison M; Rice, John P; Bierut, Laura J; Madden, Pamela A F

    2008-06-01

    The gamma-aminobutyric acid receptor A (GABRA) gene clusters on chromosomes 4 and 5 have been examined previously for their association with alcohol and drug dependence phenotypes. Compelling evidence suggests that GABRA2 is associated with alcohol and drug dependence. However, no study has investigated whether genes in the GABA(A) gene clusters are associated with nicotine dependence, an important phenotype with a high correlation to persistent smoking, the single most preventable cause of mortality world-wide. Using data on 1050 nicotine-dependent cases and 879 non-dependent smoking controls, we used logistic regression to examine the association between single nucleotide polymorphisms (SNPs) in 13 genes in the GABA(A) receptor system as well as GABBR2 (a GABA(B) gene). We found evidence for association between four SNPs in GABRA4, two SNPs in GABRA2 and one SNP in GABRE with nicotine dependence. These included a synonymous polymorphism in GABRA2 (rs279858), lying in a highly conserved region, which has been shown previously to be associated with alcohol and drug dependence. A non-synonymous polymorphism (rs16859834/rs2229940) in GABRA4, also highly conserved, was associated at P-value of 0.03. Significant haplotypes associated with nicotine dependence were found for GABRA2. No evidence for epistatic interactions were noted. Our study did not find evidence for an association between GABBR2 gene and nicotine dependence. Given the potential role of compounds that enhance GABAergic neurotransmission in smoking cessation research, these findings have enormous potential for informing the wider field of addiction research.

  8. Synergistic antipruritic effects of gamma aminobutyric acid A and B agonists in a mouse model of atopic dermatitis.

    Science.gov (United States)

    Cevikbas, Ferda; Braz, Joao M; Wang, Xidao; Solorzano, Carlos; Sulk, Mathias; Buhl, Timo; Steinhoff, Martin; Basbaum, Allan I

    2017-08-01

    Despite recent insights into the pathophysiology of acute and chronic itch, chronic itch remains an often intractable condition. Among major contributors to chronic itch is dysfunction of spinal cord gamma aminobutyric acidergic (GABAergic) inhibitory controls. We sought to test the hypothesis that selective GABA agonists as well as cell transplant-derived GABA are antipruritic against acute itch and in a transgenic mouse model of atopic dermatitis produced by overexpression of the T H 2 cell-associated cytokine, IL-31 (IL-31Tg mice). We injected wild-type and IL-31Tg mice with combinations of GABA-A (muscimol) or GABA-B (baclofen) receptor agonists 15 to 20 minutes prior to injection of various pruritogens (histamine, chloroquine, or endothelin-1) and recorded spontaneous scratching before and after drug administration. We also tested the antipruritic properties of intraspinal transplantation of precursors of GABAergic interneurons in the IL-31Tg mice. Systemic muscimol or baclofen are antipruritic against both histamine-dependent and -independent pruritogens, but the therapeutic window using either ligand alone was very small. In contrast, combined subthreshold doses of baclofen and muscimol produced a significant synergistic antipruritic effect, with no sedation. Finally, transplant-mediated long-term enhancement of GABAergic signaling not only reduced spontaneous scratching in the IL-31Tg mice but also dramatically resolved the associated skin lesions. Although additional research is clearly needed, existing approved GABA agonists should be considered in the management of chronic itch, notably atopic dermatitis. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  9. Gamma-aminobutyric acid and related molecules in the sea fan Eunicella cavolini (Cnidaria: Octocorallia): a biochemical and immunohistochemical approach.

    Science.gov (United States)

    Girosi, Laura; Ferrando, Sara; Beltrame, Francesco; Ciarcia, Gaetano; Diaspro, Alberto; Fato, Marco; Magnone, Mirko; Raiteri, Luca; Ramoino, Paola; Tagliafierro, Grazia

    2007-07-01

    The aim of this study has been the biochemical demonstration of the presence of gamma-aminobutyric acid (GABA) in the Mediterranean sea fan Eunicella cavolini by means of high-performance liquid chromatography, and the description of the distribution pattern of GABA and its related molecules, glutamic acid decarboxylase (GAD), vesicular GABA transporter (VGAT) and one of the GABA receptors (GABA(B) R) by immunohistochemical methods. The interrelationships of GABA, GAD and GABA receptor immunoreactivity have been established by using double-immunohistochemical methods and confocal microscopy. The immunodetection of monoclonal and/or polyclonal antibodies has revealed GABA immunoreactivity throughout the polyp tissue, both in neuronal and non-neuronal elements. GAD immunoreactivity has been mostly localized in the neuronal compartment, contacting epithelial and muscular elements. GABA(B) R immunoreactivity appears particularly intense in the nematocytes and in the oocyte envelope; its presence in GAD-immunoreactive neurons in the tentacles suggests an autocrine type of regulation. Western blot analysis has confirmed that a GABA(B) R, with a molecular weight of 142 kDa, similar to that of rat brain, is present in E. cavolini polyp tissue. The identification of the sites of the synthesis, vesicular transport, storage and reception of GABA strongly suggests the presence of an almost complete set of GABA-related molecules for the functioning of the GABAergic system in this simple nervous system. The distribution of these different immunoreactivities has allowed us to hypothesize GABA involvement in nematocyst discharge, in body wall and enteric muscular contraction, in neuronal integration and in male gametocyte differentiation.

  10. Delta Subunit-Containing Gamma-Aminobutyric Acid A Receptor Disinhibits Lateral Amygdala and Facilitates Fear Expression in Mice.

    Science.gov (United States)

    Liu, Zhi-Peng; He, Qing-Hai; Pan, Han-Qing; Xu, Xiao-Bin; Chen, Wen-Bing; He, Ye; Zhou, Jin; Zhang, Wen-Hua; Zhang, Jun-Yu; Ying, Xiao-Ping; Han, Ren-Wen; Li, Bao-Ming; Gao, Tian-Ming; Pan, Bing-Xing

    2017-06-15

    Maintaining gamma-aminobutyric acidergic (GABAergic) inhibition in the amygdala within a physiological range is critical for the appropriate expression of emotions such as fear and anxiety. The synaptic GABA type A receptor (GABA A R) is generally known to mediate the primary component of amygdala inhibition and prevent inappropriate expression of fear. However, little is known about the contribution of the extrasynaptic GABA A R to amygdala inhibition and fear. By using mice expressing green fluorescent protein in interneurons (INs) and lacking the δ subunit-containing GABA A R (GABA A (δ)R), which is exclusively situated in the extrasynaptic membrane, we systematically investigated the role of GABA A (δ)R in regulating inhibition in the lateral amygdala (LA) and fear learning using the combined approaches of immunohistochemistry, electrophysiology, and behavior. In sharp contrast to the established role of synaptic GABA A R in mediating LA inhibition, we found that either pharmacological or physiological recruitment of GABA A (δ)R resulted in the weakening of GABAergic transmission onto projection neurons in LA while leaving the glutamatergic transmission unaltered, suggesting disinhibition by GABA A (δ)R. The disinhibition arose from IN-specific expression of GABA A (δ)R with its activation decreasing the input resistance of local INs and suppressing their activation. Genetic deletion of GABA A (δ)R attenuated its role in suppressing LA INs and disinhibiting LA. Importantly, the GABA A (δ)R facilitated long-term potentiation in sensory afferents to LA and permitted the expression of learned fear. Our findings suggest that GABA A (δ)R serves as a brake rather than a mediator of GABAergic inhibition in LA. The disinhibition by GABA A (δ)R may help to prevent excessive suppression of amygdala activity and thus ensure the expression of emotion. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  11. Chronic noise stress-induced alterations of glutamate and gamma-aminobutyric acid and their metabolism in the rat brain.

    Science.gov (United States)

    Kazi, Amajad Iqbal; Oommen, Anna

    2014-01-01

    Chronic stress induces neurochemical changes that include neurotransmitter imbalance in the brain. Noise is an environmental factor inducing stress. Chronic noise stress affects monoamine neurotransmitter systems in the central nervous system. The effect on other excitatory and inhibitory neurotransmitter systems is not known. The aim was to study the role of chronic noise stress on the glutamatergic and gamma-aminobutyric acid (GABA)ergic systems of the brain. Female Wistar rats (155 ± 5 g) were unintentionally exposed to noise due to construction (75-95 db, 3-4 hours/day, 5 days a week for 7-8 weeks) in the vicinity of the animal care facility. Glutamate/GABA levels and their metabolic enzymes were evaluated in different rat brain regions (cortex, hippocampus, striatum, and cerebellum) and compared with age and gender matched nonexposed rats. Chronic noise stress decreased glutamate levels and glutaminase activity 27% and 33% in the cortex, 15% and 24% in the cerebellum. Glutamate levels increased 10% in the hippocampus, 28% in striatum and glutaminase activity 15% in striatum. Glutamine synthetase activity increased significantly in all brain regions studied, that is, cortex, hippocampus, striatum, and cerebellum (P Noise stress-increased GABA levels and glutamate alpha decarboxylase activity 20% and 45% in the cortex, 13% and 28% in the hippocampus respectively. GABA levels and glutamate alpha decarboxylase activity decreased 15% and 14%, respectively in the striatum. GABA transaminase activity was significantly reduced in the cortex (55%), hippocampus (17%), and cerebellum (33%). Chronic noise stress differentially affected glutamatergic and GABAergic neurotransmitter systems in the rat brain, which may alter glutamate and GABA neurotransmission.

  12. Hydroxylated analogues of 5-aminovaleric acid as 4-aminobutyric acidB receptor antagonists

    DEFF Research Database (Denmark)

    Kristiansen, U; Hedegaard, A; Herdeis, C

    1992-01-01

    The (R) and (S) forms of 5-amino-2-hydroxyvaleric acid (2-OH-DAVA) and 5-amino-4-hydroxyvaleric acid (4-OH-DAVA) were designed as structural hybrids of the 4-aminobutyric acidB (GABAB) agonist (R)-(-)-4-amino-3-hydroxybutyric acid [(R)-(-)-3-OH-GABA] and the GABAB antagonist 5-aminovaleric acid...

  13. [Construction of a recombinant Escherichia coli BL21/ pET-28a-lpgad and the optimization of transformation conditions for the efficient production of gamma-aminobutyric acid].

    Science.gov (United States)

    Tian, Lingzhi; Xu, Meijuan; Rao, Zhiming

    2012-01-01

    In order to enhance gamma-aminobutyric acid production from L-glutamate efficiently, we amplified the key enzyme glutamate decarboxylase (GAD) encoding gene lpgad from the strain Lactobacillus plantarum GB 01-21 which was obtained by way of multi-mutagenesis and overexpressed it in E. coli BL21. Then we purified GAD by Ni-NTA affinity chromatography and characterized the enzyme to optimize the conditions of the whole-cell transformation. The results showed that the recombinant E. coli BL21 (pET-28a-lpgad) produced 8.53 U/mg GAD, which was increased by 3.24 fold compared with the GAD activity in L. plantarum. The optimum pH and temperature of the enzyme were pH 4.8 and 37 degrees C, respectively. At the same time, we found that Ca2+ and Mg2+ could increase the activity significantly. Based on this, we investigated gamma-aminobutyric acid transformation in 5 L fermentor under the optimum transformation conditions. Accordingly, the yield of gamma-aminobutyric acid was 204.5 g/L at 24 h when the 600 g L-glutamate was added and the mole conversion rate had reached 97.92%. The production of gamma-aminobutyric acid was improved by 42.5% compared with that under the unoptimized transformation conditions. This paved a way for the gamma-aminobutyric acid construction of the industrial applications.

  14. The gamma-aminobutyric acid type B (GABAB receptor agonist baclofen inhibits morphine sensitization by decreasing the dopamine level in rat nucleus accumbens

    Directory of Open Access Journals (Sweden)

    Fu Zhenyu

    2012-07-01

    Full Text Available Abstract Background Repeated morphine exposure can induce behavioral sensitization. There are evidences have shown that central gamma-aminobutyric acid (GABA system is involved in morphine dependence. However, the effect of a GABAB receptor agonist baclofen on morphine-induced behavioral sensitization in rats is unclear. Methods We used morphine-induced behavioral sensitization model in rat to investigate the effects of baclofen on behavioral sensitization. Moreover, dopamine release in the shell of the nucleus accumbens was evaluated using microdialysis assay in vivo. Results The present study demonstrated that morphine challenge (3 mg/kg, s.c. obviously enhanced the locomotor activity following 4-day consecutive morphine administration and 3-day withdrawal period, which indicated the expression of morphine sensitization. In addition, chronic treatment with baclofen (2.5, 5 mg/kg significantly inhibited the development of morphine sensitization. It was also found that morphine challenge 3 days after repeated morphine administration produced a significant increase of extracellular dopamine release in nucleus accumbens. Furthermore, chronic treatment with baclofen decreased the dopamine release induced by morphine challenge. Conclusions Our results indicated that gamma-aminobutyric acid system plays an important role in the morphine sensitization in rat and suggested that behavioral sensitization is a promising model to study the mechanism underlying drug abuse.

  15. Determination of glutamic acid and gamma-aminobutyric acid in Ringer's solution without desalination at the femtomole level by gas chromatography chemical ionization mass spectrometry.

    Science.gov (United States)

    Murayama, K; Shindo, N; Mineki, R; Ohta, K

    1981-04-01

    For the quantification of glutamic acid in Ringer's solution, pentafluoropropionic methyl ester was the most sensitive derivative. The detectable concentration was 0.01 microM glutamic acid in Ringer's solution; the amount of the preparation was 1 pmol and the injection into a gas chromatograph mass spectrometer was 10 fmol. For the quantification of gamma-aminobutyric acid in Ringer's solution, the trifluoroacetal-hexafluoropropionyl ester was quantification of gamma-aminobutyric acid in Ringer's solution, the trifluoroacetal-hexafluoropropionyl ester was detectable at a concentration of 0.01 microM. Ringer's salts facilitated acylation in the order heptafluorobutyric anhydride greater than pentafluoropropionic anhydride greater than trifluoroacetic anhydride. The effect depended on esterification of carboxy groups in the order methyl ester greater than hexafluoropropionyl ester greater than butyl ester. Sodium carbonate, sodium acetate and sodium citrate also facilitated acylation with pentafluoroproionic anhydride, while sodium phosphate inhibited the acylation and sodium sulfate inhibited it slightly. The pentafluoropropionic methyl ester of glutamic acid was stable for up to 10 days, when it was dissolved in acetone and stored at -18 degrees C.

  16. Gamma-Aminobutyric Acid Increases the Production of Short-Chain Fatty Acids and Decreases pH Values in Mouse Colon.

    Science.gov (United States)

    Xie, Min; Chen, Hai-Hong; Nie, Shao-Ping; Yin, Jun-Yi; Xie, Ming-Yong

    2017-04-20

    Gamma-Aminobutyric acid (GABA) could regulate physiological functions in the gastrointestinal tract. The present study aimed to investigate the effect of GABA on colon health in mice. The female Kunming mice were given GABA at doses of 5, 10, 20 and 40 mg/kg/d for 14 days. Afterwards, the short-chain fatty acids (SCFAs) concentrations, pH values, colon index, colon length and weight of colonic and cecal contents were determined to evaluate the effects of GABA on colon health. The results showed that intake of GABA could increase the concentrations of acetate, propionate, butyrate and total SCFAs in colonic and cecal contents, as well as the weight of colonic and cecal contents. The colon index and length of the 40 mg/kg/d GABA-treated group were significantly higher than those of the control group ( p colonic and cecal contents was also observed. These results suggest that GABA may improve colon health.

  17. 7T Proton Magnetic Resonance Spectroscopy of Gamma-Aminobutyric Acid, Glutamate, and Glutamine Reveals Altered Concentrations in Patients With Schizophrenia and Healthy Siblings

    DEFF Research Database (Denmark)

    Thakkar, Katharine N; Rösler, Lara; Wijnen, Jannie P

    2017-01-01

    BACKGROUND: The N-methyl-D-aspartate receptor hypofunction model of schizophrenia predicts dysfunction in both glutamatergic and gamma-aminobutyric acidergic (GABAergic) transmission. We addressed this hypothesis by measuring GABA, glutamate, glutamine, and the sum of glutamine plus glutamate...... concentrations in vivo in patients with schizophrenia using proton magnetic resonance spectroscopy at 7T, which allows separation of metabolites that would otherwise overlap at lower field strengths. In addition, we investigated whether altered levels of GABA, glutamate, glutamine, and the sum of glutamine plus......, and 24 healthy nonrelatives. Glutamate, glutamine, and GABA were measured cortically and subcortically in bilateral basal ganglia and occipital cortex. RESULTS: Patients with schizophrenia had reduced cortical GABA compared with healthy relatives and the combined sample of healthy relatives and healthy...

  18. Effects of inhibitors of protein synthesis and intracellular transport on the gamma-aminobutyric acid agonist-induced functional differentiation of cultured cerebellar granule cells

    DEFF Research Database (Denmark)

    Belhage, B; Hansen, Gert Helge; Meier, E

    1990-01-01

    an intracellular and a plasma membrane localization of the receptors. In all experiments cultures treated with THIP alone served as controls. The inhibitors of protein synthesis totally abolished the ability of THIP to induce low-affinity GABA receptors. In contrast, the inhibitors of intracellular transport......The effect of inhibitors of protein synthesis (actinomycin D, cycloheximide), proteases (leupeptin), and intracellular transport (colchicine, monensin) on the gamma-aminobutyric acid (GABA) agonist [4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP)]-induced changes in morphological...... as well as the protease inhibitor did not affect this parameter. However, studies of effects of GABA on transmitter release from monensin-treated cultures showed that transmitter release could not be inhibited by GABA in these cells in spite of the presence of low-affinity GABA receptors in the membrane...

  19. Serotonin Transporter (5-HTT) and gamma-Aminobutyric Acid Receptor Subunit beta3 (GABRB3) Gene Polymorphisms are not Associated with Autism in the IMGSA Families

    DEFF Research Database (Denmark)

    Maestrini, E.; Lai, C.; Marlow, A.

    1999-01-01

    on the collection of families grom the International Molecular Genetic Study of Autism (IMGSA) Consortium, using the transmission disequilibrium test. Two polymorphisms in the 5-HTT gene (a functional insertion-deletion polymorphism in the promoter and a variable nubmer tandem repeat in the second intron) were...... examined in 90 families comprising 174 affected individuals. Furthermore, seven microsatellite markers spanning the 15q11-q13 region were studied in 94 families with 182 affected individuals. No significant evidence of association or linkage was found at any of the markers tested, indicating that the 5-HTT......Previous studies have suggested that the serotonin transporter (5-HTT) gene and the gamma-aminobutyric acid receptor subunit beta3 (GABRB3) gene, or other genes in the 15q11-q13 region, are possibly involved in susceptibility to autism. To test this hypothesis we performed an association study...

  20. Comparative proteomic analysis of gamma-aminobutyric acid responses in hypoxia-treated and untreated melon roots.

    Science.gov (United States)

    Fan, Longquan; Wu, Xiaolei; Tian, Zhen; Jia, Kaizhi; Pan, Yinghong; Li, Jingrui; Gao, Hongbo

    2015-08-01

    Hypoxia is one of the main environmental stresses that accounts for decreasing crop yield. To further investigate the mechanisms whereby exogenous GABA alleviates hypoxia injury to melon seedlings, a comparative proteomic analysis was performed using roots subjected to normal aeration and hypoxia conditions with or without GABA (5mM). The results indicated that protein spots on gels after hypoxia and hypoxia+GABA treatment were significantly changed. Three "matched sets" were analyzed from four treatments, and 13 protein spots with large significant differences in expression were identified by MALDI-TOF/TOF mass spectrometry. Exogenous GABA treatment enhanced the expression of protein in cytosolic phosphoglycerate kinase 1, exaA2 gene product, dnaJ and myb-like DNA-binding domain-containing proteins, as well as elongation factor-1 alpha and hypothetical proteins in hypoxia-induced roots. However, the hypoxia+GABA treated roots had a significantly lower expression of proteins including malate dehydrogenase, nucleoside diphosphate kinase, disease resistance-like protein, disulfide isomerase, actin, ferrodoxin NADP oxidoreductase, glutathione transferase, netting associated peroxidase. This paper describes the effect of GABA on melon plants under hypoxia-induced stress using proteomics, and supports the alleviating function of GABA in melon plants grown under hypoxic conditions. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Restless legs syndrome and central nervous system gamma-aminobutyric acid: preliminary associations with periodic limb movements in sleep and restless leg syndrome symptom severity.

    Science.gov (United States)

    Winkelman, John W; Schoerning, Laura; Platt, Sam; Jensen, J Eric

    2014-10-01

    Previous research has demonstrated abnormalities in glutamate and N-acetyl aspartate (NAA) in the thalamus in individuals with restless legs syndrome (RLS) compared with healthy matched controls. However, levels of these transmitters in other RLS-related brain areas and levels of the most common inhibitory neurotransmitter, gamma-aminobutyric acid (GABA), have not been assessed. This study examined GABA, glutamate, and NAA levels in the dorsal anterior cingulate cortex (ACC), thalamus and cerebellum with the use of proton magnetic resonance spectroscopy ((1)H-MRS) at 4 tesla (4 T) and Megapress difference-editing in 18 subjects with RLS and a matched control group without RLS. Actigraphy was performed on the nights before scans to assess periodic limb movements of sleep (PLMS). Levels of GABA, glutamate, and NAA were no different between RLS and control subjects in any of the three voxels of interest. However, GABA levels were positively correlated with both PLM indices and RLS severity in the thalamus and negatively with both of these measures in the cerebellum in RLS subjects. In addition, NAA levels were higher in the ACC in RLS than in controls. Our preliminary data suggest that known cerebellar-thalamic interactions may modulate the intensity of RLS sensory and motor symptoms. In addition, anterior cingulate cortex may be associated with the affective components of the painful symptoms in this disorder. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Alternate cadmium exposure differentially affects the content of gamma-aminobutyric acid (GABA) and taurine within the hypothalamus, median eminence, striatum and prefrontal cortex of male rats

    Energy Technology Data Exchange (ETDEWEB)

    Esquifino, A.I. [Dept. de Bioquimica y Biologia Molecular III, Universidad Complutense, Madrid (Spain); Seara, R.; Fernandez-Rey, E.; Lafuente, A. [Lab. de Toxicologia, Universidad de Vigo, Orense (Spain)

    2001-05-01

    This work examines changes of gamma aminobutyric acid (GABA) and taurine contents in the hypothalamus, striatum and prefrontal cortex of the rat after an alternate schedule of cadmium administration. Age-associated changes were also evaluated, of those before puberty and after adult age. In control rats GABA content decreased with age in the median eminence and in anterior, mediobasal and posterior hypothalamus, prefrontal cortex and the striatum. Taurine content showed similar results with the exception of mediobasal hypothalamus and striatum, where no changes were detected. In pubertal rats treated with cadmium from 30 to 60 days of life, GABA content significantly decreased in all brain regions except in the striatum. When cadmium was administered from day 60 to 90 of life, GABA content was significantly changed in prefrontal cortex only compared with the age matched controls. Taurine content showed similar results in pubertal rats, with the exception of the median eminence and the mediobasal hypothalamus, neither of which showed a change. However, when cadmium was administered to rats from day 60 to 90 of life, taurine content only changed in prefrontal cortex compared with the age matched controls. These results suggest that cadmium differentially affects GABA and taurine contents within the hypothalamus, median eminence, striatum and prefrontal cortex as a function of age. (orig.)

  3. Alternate cadmium exposure differentially affects the content of gamma-aminobutyric acid (GABA) and taurine within the hypothalamus, median eminence, striatum and prefrontal cortex of male rats

    International Nuclear Information System (INIS)

    Esquifino, A.I.; Seara, R.; Fernandez-Rey, E.; Lafuente, A.

    2001-01-01

    This work examines changes of gamma aminobutyric acid (GABA) and taurine contents in the hypothalamus, striatum and prefrontal cortex of the rat after an alternate schedule of cadmium administration. Age-associated changes were also evaluated, of those before puberty and after adult age. In control rats GABA content decreased with age in the median eminence and in anterior, mediobasal and posterior hypothalamus, prefrontal cortex and the striatum. Taurine content showed similar results with the exception of mediobasal hypothalamus and striatum, where no changes were detected. In pubertal rats treated with cadmium from 30 to 60 days of life, GABA content significantly decreased in all brain regions except in the striatum. When cadmium was administered from day 60 to 90 of life, GABA content was significantly changed in prefrontal cortex only compared with the age matched controls. Taurine content showed similar results in pubertal rats, with the exception of the median eminence and the mediobasal hypothalamus, neither of which showed a change. However, when cadmium was administered to rats from day 60 to 90 of life, taurine content only changed in prefrontal cortex compared with the age matched controls. These results suggest that cadmium differentially affects GABA and taurine contents within the hypothalamus, median eminence, striatum and prefrontal cortex as a function of age. (orig.)

  4. Use of sourdough fermentation and pseudo-cereals and leguminous flours for the making of a functional bread enriched of gamma-aminobutyric acid (GABA).

    Science.gov (United States)

    Coda, Rossana; Rizzello, Carlo Giuseppe; Gobbetti, Marco

    2010-02-28

    Lactobacillus plantarum C48 and Lactococcus lactis subsp. lactis PU1, previously selected for the biosynthesis of gamma-aminobutyric acid (GABA), were used for sourdough fermentation of cereal, pseudo-cereal and leguminous flours. Chickpea, amaranth, quinoa and buckwheat were the flours most suitable to be enriched of GABA. The parameters of sourdough fermentation were optimized. Addition of 0.1mM pyridoxal phosphate, dough yield of 160, inoculum of 5 x 10(7)CFU/g of starter bacteria and fermentation for 24h at 30 degrees C were found to be the optimal conditions. A blend of buckwheat, amaranth, chickpea and quinoa flours (ratio 1:1:5.3:1) was selected and fermented with baker's yeast (non-conventional flour bread, NCB) or with Lb. plantarum C48 sourdough (non-conventional flour sourdough bread, NCSB) and compared to baker's yeast started wheat flour bread (WFB). NCSB had the highest concentration of free amino acids and GABA (ca. 4467 and 504 mg/kg, respectively). The concentration of phenolic compounds and antioxidant activity of NCSB bread was the highest, as well as the rate of in vitro starch hydrolysis was the lowest. Texture analysis showed that sourdough fermentation enhances several characteristics of NCSB with respect to NCB, thus approaching the features of WFB. Sensory analysis showed that sourdough fermentation allowed to get good palatability and overall taste appreciation. (c) 2009 Elsevier B.V. All rights reserved.

  5. Psychological stress-reducing effect of chocolate enriched with gamma-aminobutyric acid (GABA) in humans: assessment of stress using heart rate variability and salivary chromogranin A.

    Science.gov (United States)

    Nakamura, H; Takishima, T; Kometani, T; Yokogoshi, H

    2009-01-01

    We studied the psychological stress-reducing effect of chocolate enriched with gamma-aminobutyric acid (GABA), on stress induced by an arithmetic task using changes of heart rate variability (HRV) and salivary chromogranin A (CgA). Subjects ingested 10 g chocolate enriched with 28 mg GABA (GABA chocolate); 15 min after the ingestion, subjects were assigned an arithmetic task for 15 min. After the task, an electrocardiogram was recorded and saliva samples were collected. HRV was determined from the electrocardiogram, and the activity of the autonomic nervous system was estimated through HRV. The CgA concentration of all saliva samples, an index for acute psychological stress, was measured. From HRV, those taking GABA chocolate made a quick recovery to the normal state from the stressful state. The CgA value after the task in those taking GABA chocolate did not increased in comparison with that before ingestion. From these results, GABA chocolate was considered to have a psychological stress-reducing effect.

  6. Time-course study and effects of drying method on concentrations of gamma-aminobutyric acid, flavonoids, anthocyanin, and 2''-hydroxynicotianamine in leaves of buckwheats.

    Science.gov (United States)

    Suzuki, Tatsuro; Watanabe, Masami; Iki, Makiko; Aoyagi, Yasuo; Kim, Sun-Ju; Mukasa, Yuji; Yokota, Satoshi; Takigawa, Shigenobu; Hashimoto, Naoto; Noda, Takahiro; Yamauchi, Hiroaki; Matsuura-Endo, Chie

    2009-01-14

    Concentrations of gamma-aminobutyric acid (GABA), rutin, minor flavonoids (such as orientin), anthocyanin, and 2''-hydroxynicotianamine (2HN) were quantified in the leaves of common and tartary buckwheat (Fagopyrum esculentum Moench and Fagopyrum tataricum Gaertn., respectively), at 14, 28, and 42 days after sowing (DAS). GABA and rutin concentrations peaked at 42 DAS, whereas anthocyain, 2HN, and minor flavonoid concentrations declined with the age of the plants. However, at 42 DAS, anthocyanin concentrations in the leaves of tartary buckwheat Hokkai T10 leaves were at least 10-fold greater than in the other buckwheats tested. In addition, the effects on target compound concentrations and 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity of three different drying methods (20 h at 40 degrees C, 7 h at 70 degrees C, or lyophilization) were investigated. In general, the drying method had no significant effect on the parameters tested. These results indicate that, in terms of GABA, rutin, and anthocyanin concentrations, leaf powder from 42 day old Hokkai T10 has the potential to be a useful food ingredient, such as Ao-jiru juice.

  7. Effects of Traumatic Stress Induced in the Juvenile Period on the Expression of Gamma-Aminobutyric Acid Receptor Type A Subunits in Adult Rat Brain

    Directory of Open Access Journals (Sweden)

    Cui Yan Lu

    2017-01-01

    Full Text Available Studies have found that early traumatic experience significantly increases the risk of posttraumatic stress disorder (PTSD. Gamma-aminobutyric acid (GABA deficits were proposed to be implicated in development of PTSD, but the alterations of GABA receptor A (GABAAR subunits induced by early traumatic stress have not been fully elucidated. Furthermore, previous studies suggested that exercise could be more effective than medications in reducing severity of anxiety and depression but the mechanism is unclear. This study used inescapable foot-shock to induce PTSD in juvenile rats and examined their emotional changes using open-field test and elevated plus maze, memory changes using Morris water maze, and the expression of GABAAR subunits (γ2, α2, and α5 in subregions of the brain in the adulthood using western blotting and immunohistochemistry. We aimed to observe the role of GABAAR subunits changes induced by juvenile trauma in the pathogenesis of subsequent PTSD in adulthood. In addition, we investigated the protective effects of exercise for 6 weeks and benzodiazepine (clonazepam for 2 weeks. This study found that juvenile traumatic stress induced chronic anxiety and spatial memory loss and reduced expression of GABAAR subunits in the adult rat brains. Furthermore, exercise led to significant improvement as compared to short-term BZ treatment.

  8. Efficient gamma-aminobutyric acid bioconversion by employing synthetic complex between glutamate decarboxylase and glutamate/GABA antiporter in engineered Escherichia coli.

    Science.gov (United States)

    Le Vo, Tam Dinh; Ko, Ji-seun; Park, Si Jae; Lee, Seung Hwan; Hong, Soon Ho

    2013-08-01

    Gamma-aminobutyric acid (GABA) is a precursor of one of the most promising heat-resistant biopolymers, Nylon-4, and can be produced by the decarboxylation of monosodium glutamate (MSG). In this study, a synthetic protein complex was applied to improve the GABA conversion in engineered Escherichia coli. Complexes were constructed by assembling a single protein-protein interaction domain SH3 to the glutamate decarboxylase (GadA and GadB) and attaching a cognate peptide ligand to the glutamate/GABA antiporter (GadC) at the N-terminus, C-terminus, and the 233rd amino acid residue. When GadA and GadC were co-overexpressed via the C-terminus complex, a GABA concentration of 5.65 g/l was obtained from 10 g/l MSG, which corresponds to a GABA yield of 93 %. A significant increase of the GABA productivity was also observed where the GABA productivity increased 2.5-fold in the early culture period due to the introduction of the synthetic protein complex. The GABA pathway efficiency and GABA productivity were enhanced by the introduction of the complex between Gad and glutamate/GABA antiporter.

  9. Sulfur amino acid metabolism in the developing rhesus monkey brain: subcellular studies of taurine, cysteinesulfinic acid decarboxylase, gamma-aminobutyric acid, and glutamic acid decarboxylase.

    Science.gov (United States)

    Rassin, D K; Sturman, J A; Gaull, G E

    1981-09-01

    Taurine, cysteinesulfinic acid decarboxylase (CSAD), glutamate, gamma-aminobutyric acid (GABA), and glutamic acid decarboxylase (GAD) were measured in subcellular fractions prepared from occipital lobe of fetal and neonatal rhesus monkeys. In addition, the distribution of [35S]taurine in subcellular fractions was determined after administration to the fetus via the mother, to the neonate via administration to the mother prior to birth, and directly to the neonate at various times after birth. CSAD, glutamate, GABA, and GAD all were found to be low or unmeasurable in early fetal life and to increase during late fetal and early neonatal life to reach values found in the mother. Taurine was present in large amounts in early fetal life and decreased slowly during neonatal life, arriving at amounts found in the mother not until after 150 days of age. Significant amounts of taurine, CSAD, GABA, and GAD were associated with nerve ending components with some indication that the proportion of brain taurine found in these organelles increases during development. All subcellular pools of taurine were rapidly labeled by exogenously administered [35S]taurine. The subcellular distribution of all the components measured was compatible with the neurotransmitter or putative neurotransmitter functions of glutamate, GABA, and taurine. The large amount of these three amino acids exceeds that required for such function. The excess of glutamate and GABA may be used as a source of energy. The function of the excess of taurine is still not clear, although circumstantial evidence favors an important role in the development and maturation of the CNS.

  10. A putrescine-inducible pathway comprising PuuE-YneI in which gamma-aminobutyrate is degraded into succinate in Escherichia coli K-12.

    Science.gov (United States)

    Kurihara, Shin; Kato, Kenji; Asada, Kei; Kumagai, Hidehiko; Suzuki, Hideyuki

    2010-09-01

    Gamma-aminobutyrate (GABA) is metabolized to succinic semialdehyde by GABA aminotransferase (GABA-AT), and the succinic semialdehyde is subsequently oxidized to succinate by succinic semialdehyde dehydrogenase (SSADH). In Escherichia coli, there are duplicate GABA-ATs (GabT and PuuE) and duplicate SSADHs (GabD and YneI). While GabT and GabD have been well studied previously, the characterization and expression analysis of PuuE and YneI are yet to be investigated. By analyzing the amino acid profiles in cells of DeltapuuE and/or DeltagabT mutants, this study demonstrated that PuuE plays an important role in GABA metabolism in E. coli cells. The similarity of the amino acid sequences of PuuE and GabT is 67.4%, and it was biochemically demonstrated that the catalytic center of GabT is conserved as an amino acid residue important for the enzymatic activity in PuuE as Lys-247. However, the regulation of expression of PuuE is significantly different from that of GabT. PuuE is induced by the addition of putrescine to the medium and is repressed by succinate and low aeration conditions; in contrast, GabT is almost constitutive. Similarly, YneI is induced by putrescine, while GabD is not. For E. coli, PuuE is important for utilization of putrescine as a sole nitrogen source and both PuuE and YneI are important for utilization of putrescine as a sole carbon source. The results demonstrate that the PuuE-YneI pathway was a putrescine-inducible GABA degradation pathway for utilizing putrescine as a nutrient source.

  11. Modulation of the release of norepinephrine by gamma-aminobutyric acid and morphine in the frontal cerebral cortex of the rat

    Energy Technology Data Exchange (ETDEWEB)

    Peoples, R.W.

    1989-01-01

    Agents that enhance gamma-aminobutyric acid, or GABA, neurotransmission modulate certain effects of opioids, such as analgesia. Opioid analgesia is mediated in part by norepinephrine in the forebrain. In this study, the interactions between morphine and GABAergic agents on release of ({sup 3}H) norepinephrine from rat frontal cerebral cortical slices were examined. GABA, 5 {times} 10{sup {minus}5}-10{sup {minus}3} M, enhanced potassium stimulated ({sup 3}H) norepinephrine release and reversed the inhibitory effect of morphine in a noncompetitive manner. GABA did not enhance release of ({sup 3}H) norepinephrine stimulated by the calcium ionophore A23187. The effect of GABA was reduced by the GABA{sub A} receptor antagonists bicuculline methiodide or picrotoxin, and by the selective inhibitor of GABA uptake SKF 89976A, but was blocked completely only when bicuculline methiodide and SKF 89976A were used in combination. The GABA{sub A} agonist muscimol, 10{sup {minus}4} M, mimicked the effect of GABA, but the GABA{sub B} agonist ({plus minus})baclofen, 10{sup {minus}4} M, did not affect the release of ({sup 3}H) norepinephrine in the absence or the presence of morphine. Thus GABA appears to produce this effect by stimulating GABA uptake and GABA{sub A}, but not GABA{sub B}, receptors. In contrast to the results that would be predicted for an event involving GABA{sub A} receptors, however, the effect of GABA did not desensitize, and benzodiazepine agonists did not enhance the effect of GABA at any concentration tested between 10{sup {minus}8} and 10{sup {minus}4} M. Thus these receptors may constitute a subclass of GABA{sub A} receptors. These results support a role of GABA uptake and GABA{sub A} receptors in enhancing the release of norepinephrine and modulating its inhibition by opioids in the frontal cortex of the rat.

  12. Dual orexin receptor antagonists show distinct effects on locomotor performance, ethanol interaction and sleep architecture relative to gamma-aminobutyric acid-A receptor modulators

    Directory of Open Access Journals (Sweden)

    Andres D. Ramirez

    2013-12-01

    Full Text Available Dual orexin receptor antagonists (DORAs are a potential treatment for insomnia that function by blocking both the orexin 1 and orexin 2 receptors. The objective of the current study was to further confirm the impact of therapeutic mechanisms targeting insomnia on locomotor coordination and ethanol interaction using DORAs and gamma-aminobutyric acid (GABA-A receptor modulators of distinct chemical structure and pharmacologic properties in the context of sleep-promoting potential. The current study compared rat motor co-ordination after administration of DORAs, DORA-12 and almorexant, and GABA-A receptor modulators, zolpidem, eszopiclone and diazepam, alone or each in combination with ethanol. Motor performance was assessed by measuring time spent walking on a rotarod apparatus. Zolpidem, eszopiclone and diazepam (0.3–30 mg/kg administered orally [PO] impaired rotarod performance in a dose-dependent manner. Furthermore, all three GABA-A receptor modulators potentiated ethanol- (0.25–1.25 g/kg induced impairment on the rotarod. By contrast, neither DORA-12 (10–100 mg/kg, PO nor almorexant (30–300 mg/kg, PO impaired motor performance alone or in combination with ethanol. In addition, distinct differences in sleep architecture were observed between ethanol, GABA-A receptor modulators (zolpidem, eszopiclone and diazepam and DORA-12 in electroencephalogram studies in rats. These findings provide further evidence that orexin receptor antagonists have an improved motor side-effect profile compared with currently available sleep-promoting agents based on preclinical data and strengthen the rationale for further evaluation of these agents in clinical development.

  13. Improved fermentative production of gamma-aminobutyric acid via the putrescine route: Systems metabolic engineering for production from glucose, amino sugars, and xylose.

    Science.gov (United States)

    Jorge, João M P; Nguyen, Anh Q D; Pérez-García, Fernando; Kind, Stefanie; Wendisch, Volker F

    2017-04-01

    Gamma-aminobutyric acid (GABA) is a non-protein amino acid widespread in Nature. Among the various uses of GABA, its lactam form 2-pyrrolidone can be chemically converted to the biodegradable plastic polyamide-4. In metabolism, GABA can be synthesized either by decarboxylation of l-glutamate or by a pathway that starts with the transamination of putrescine. Fermentative production of GABA from glucose by recombinant Corynebacterium glutamicum has been described via both routes. Putrescine-based GABA production was characterized by accumulation of by-products such as N-acetyl-putrescine. Their formation was abolished by deletion of the spermi(di)ne N-acetyl-transferase gene snaA. To improve provision of l-glutamate as precursor 2-oxoglutarate dehydrogenase activity was reduced by changing the translational start codon of the chromosomal gene for 2-oxoglutarate dehydrogenase subunit E1o to the less preferred TTG and by maintaining the inhibitory protein OdhI in its inhibitory form by changing amino acid residue 15 from threonine to alanine. Putrescine-based GABA production by the strains described here led to GABA titers up to 63.2 g L -1 in fed-batch cultivation at maximum volumetric productivities up to 1.34 g L -1  h -1 , the highest volumetric productivity for fermentative GABA production reported to date. Moreover, GABA production from the carbon sources xylose, glucosamine, and N-acetyl-glucosamine that do not have competing uses in the food or feed industries was established. Biotechnol. Bioeng. 2017;114: 862-873. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  14. Gamma-aminobutyric acid (GABA) and pentobarbital induce different conformational rearrangements in the GABA A receptor alpha1 and beta2 pre-M1 regions.

    Science.gov (United States)

    Mercado, Jose; Czajkowski, Cynthia

    2008-05-30

    Gamma-aminobutyric acid (GABA) binding to GABA(A) receptors (GABA(A)Rs) triggers conformational movements in the alpha(1) and beta(2) pre-M1 regions that are associated with channel gating. At high concentrations, the barbiturate pentobarbital opens GABA(A)R channels with similar conductances as GABA, suggesting that their open state structures are alike. Little, however, is known about the structural rearrangements induced by barbiturates. Here, we examined whether pentobarbital activation triggers movements in the GABA(A)R pre-M1 regions. Alpha(1)beta(2) GABA(A)Rs containing cysteine substitutions in the pre-M1 alpha(1) (K219C, K221C) and beta(2) (K213C, K215C) subunits were expressed in Xenopus oocytes and analyzed using two-electrode voltage clamp. The cysteine substitutions had little to no effect on GABA and pentobarbital EC(50) values. Tethering chemically diverse thiol-reactive methanethiosulfonate reagents onto alpha(1)K219C and alpha(1)K221C affected GABA- and pentobarbital-activated currents differently, suggesting that the pre-M1 structural elements important for GABA and pentobarbital current activation are distinct. Moreover, pentobarbital altered the rates of cysteine modification by methanethiosulfonate reagents differently than GABA. For alpha(1)K221Cbeta(2) receptors, pentobarbital decreased the rate of cysteine modification whereas GABA had no effect. For alpha(1)beta(2)K215C receptors, pentobarbital had no effect whereas GABA increased the modification rate. The competitive GABA antagonist SR-95531 and a low, non-activating concentration of pentobarbital did not alter their modification rates, suggesting that the GABA- and pentobarbital-mediated changes in rates reflect gating movements. Overall, the data indicate that the pre-M1 region is involved in both GABA- and pentobarbital-mediated gating transitions. Pentobarbital, however, triggers different movements in this region than GABA, suggesting their activation mechanisms differ.

  15. Hydroxylated analogues of 5-aminovaleric acid as 4-aminobutyric acidB receptor antagonists

    DEFF Research Database (Denmark)

    Kristiansen, U; Hedegaard, A; Herdeis, C

    1992-01-01

    The (R) and (S) forms of 5-amino-2-hydroxyvaleric acid (2-OH-DAVA) and 5-amino-4-hydroxyvaleric acid (4-OH-DAVA) were designed as structural hybrids of the 4-aminobutyric acidB (GABAB) agonist (R)-(-)-4-amino-3-hydroxybutyric acid [(R)-(-)-3-OH-GABA] and the GABAB antagonist 5-aminovaleric acid...... (DAVA). (S)-(-)-2-OH-DAVA and (R)-(-)-4-OH-DAVA showed a moderately potent affinity for GABAB receptor sites in rat brain and showed GABAB antagonist effects in a guinea pig ileum preparation. The respective enantiomers, (R)-(+)-2-OH-DAVA and (S)-(+)-4-OH-DAVA, were markedly weaker in both test systems......-DAVA can be superimposed. These conformations may reflect the shapes adopted by these conformationally flexible compounds during their interaction with GABAB receptors. The present studies emphasize the similar, but distinct, constraints imposed on agonists and antagonists for GABAB receptors....

  16. DNA methylation at the neonatal state and at the time of diagnosis. Preliminary support for an association with the estrogen receptor 1, gamma-aminobutyric acid B receptor 1, and myelin oligodendrocyte glycoprotein in female adolescent patients with OCD

    Directory of Open Access Journals (Sweden)

    Judith Becker Nissen

    2016-03-01

    Full Text Available Obsessive-compulsive disorder (OCD is a neuropsychiatric disorder. Non-genetic factors and their interaction with genes have attracted increasing attention. Epigenetics is regarded an important interface between environmental signals and activation/repression of genomic responses. Epigenetic mechanisms have not previously been examined in OCD in children and adolescents.The aim of the present study was to examine the DNA methylation profile of selected genes in blood spots from neonates later diagnosed with OCD and in the same children/adolescents at the time of diagnosis compared with age- and sex matched controls. Furthermore, we wanted to characterize the association of the differential methylation profiles with the severity of OCD and treatment outcome.Dried and new blood spot samples were obtained from 21 female children/adolescents with verified OCD and 12 female controls. The differential methylation was analyzed using a linear model and the correlation with the severity of OCD and treatment outcome was analyzed using the Pearson correlation. We evaluated selected Illumina Infinium HumanMethylation450 BeadChip probes within and up to 100,000 bp up- and downstream of 14 genes previously associated with OCD (SLC1A1, SLC25A12, GABBR1, GAD1, DLGAP1, MOG, BDNF, OLIG2, NTRK2 and 3, ESR1, SL6A4, TPH2 and COMT.The study found no significantly differential methylation. However, preliminary support for a difference was found for the gamma-aminobutyric acid (GABA B receptor 1 (cg10234998, cg17099072 in blood samples at birth and for the estrogen receptor 1 (ESR1 (cg10939667, the myelin oligodendrocyte glycoprotein (MOG (cg16650906, and the brain-derived neurotrophic factor (BDNF (cg14080521 in blood samples at the time of diagnosis.Preliminary support for an association was observed between the methylation profiles of GABBR1 and MOG and baseline severity, treatment effect, and responder status; and between the methylation profile of ESR1 and

  17. DNA Methylation at the Neonatal State and at the Time of Diagnosis: Preliminary Support for an Association with the Estrogen Receptor 1, Gamma-Aminobutyric Acid B Receptor 1, and Myelin Oligodendrocyte Glycoprotein in Female Adolescent Patients with OCD.

    Science.gov (United States)

    Nissen, Judith Becker; Hansen, Christine Søholm; Starnawska, Anna; Mattheisen, Manuel; Børglum, Anders Dupont; Buttenschøn, Henriette Nørmølle; Hollegaard, Mads

    2016-01-01

    Obsessive-compulsive disorder (OCD) is a neuropsychiatric disorder. Non-genetic factors and their interaction with genes have attracted increasing attention. Epigenetics is regarded an important interface between environmental signals and activation/repression of genomic responses. Epigenetic mechanisms have not previously been examined in OCD in children and adolescents. The aim of the present study was to examine the DNA methylation profile of selected genes in blood spots from neonates later diagnosed with OCD and in the same children/adolescents at the time of diagnosis compared with age- and sex-matched controls. Furthermore, we wanted to characterize the association of the differential methylation profiles with the severity of OCD and treatment outcome. Dried and new blood spot samples were obtained from 21 female children/adolescents with verified OCD and 12 female controls. The differential methylation was analyzed using a linear model and the correlation with the severity of OCD and treatment outcome was analyzed using the Pearson correlation. We evaluated selected Illumina Infinium HumanMethylation450 BeadChip probes within and up to 100,000 bp up- and downstream of 14 genes previously associated with OCD (SLC1A1, SLC25A12, GABBR1, GAD1, DLGAP1, MOG, BDNF, OLIG2, NTRK2 and 3, ESR1, SL6A4, TPH2, and COMT). The study found no significantly differential methylation. However, preliminary support for a difference was found for the gamma-aminobutyric acid (GABA) B receptor 1 (cg10234998, cg17099072) in blood samples at birth and for the estrogen receptor 1 (ESR1) (cg10939667), the myelin oligodendrocyte glycoprotein (MOG) (cg16650906), and the brain-derived neurotrophic factor (BDNF) (cg14080521) in blood samples at the time of diagnosis. Preliminary support for an association was observed between the methylation profiles of GABBR1 and MOG and baseline severity, treatment effect, and responder status; and between the methylation profile of ESR1 and baseline

  18. Prefrontal gamma-aminobutyric Acid type a receptor insertion controls cue-induced relapse to nicotine seeking

    NARCIS (Netherlands)

    Lubbers, B.R.; van Mourik, Y.; Schetters, D.; Smit, A.B.; de Vries, T.J.; Spijker, S.

    2014-01-01

    Background: Current smoking cessation therapies offer limited success, as relapse rates remain high. Nicotine, which is the major component of tobacco smoke, is thought to be primarily responsible for the addictive properties of tobacco. However, little is known about the molecular mechanisms

  19. Role of gamma-aminobutyric acid in early neuronal development: studies with an embryonic neuroectodermal stem cell clone

    Czech Academy of Sciences Publication Activity Database

    Jelitai, M.; Anděrová, Miroslava; Markó, K.; Kékesi, K.; Koncz, P.; Syková, Eva; Madarász, E.

    2004-01-01

    Roč. 76, - (2004), s. 801-811 ISSN 0360-4012 R&D Projects: GA ČR GA305/02/1528; GA ČR GA305/03/1172; GA MŠk LN00A065 Institutional research plan: CEZ:AV0Z5039906 Keywords : neuronal development * calcium response Subject RIV: FH - Neurology Impact factor: 3.727, year: 2004

  20. High-resolution mapping of the [gamma]-aminobutyric acid receptor subunit [beta]3 and [alpha]5 gene cluster on chromosome 15q11-q13, and localization of breakpoints in two Angelman syndrome patients

    Energy Technology Data Exchange (ETDEWEB)

    Sinnett, D.; Wagstaff, J.; Woolf, E. (Children' s Hospital, Boston, MA (United States) Harvard Medical School, Boston, MA (United States)); Glatt, K. (Children' s Hospital, Boston, MA (United States)); Kirkness, E.J. (National Inst. of Alcohol Abuse and Alcoholism, Rockville, MD (United States))Lalande, M. (Children' s Hospital, Boston, MA (United States) Harvard Medical School, Boston, MA (United States) Howard Hughes Medical Inst., Boston, MA (United States))

    1993-06-01

    The [gamma]-aminobutyric acid (GABA[sub A]) receptors are a family of ligand-gated chloride channels constituting the major inhibitory neurotransmitter receptors in the nervous system. In order to determine the genomic organization of the GABA[sub A] receptor [beta]3 subunit gene (GABRB3) and [alpha]5 subunit gene (GABRA5) in chromosome 15q11-q13, the authors have constructed a high-resolution physical map using the combined techniques of field-inversion gel electrophoresis and phage genomic library screening. This map, which covers nearly 1.0 Mb, shows that GABRB3 and GABRA5 are separated by less than 100 kb and are arranged in a head-to-head configuration. GABRB3 encompasses approximately 250 kb, while GABRA5 is contained within 70 kb. This difference in size is due in large part to an intron of 150 kb within GABRB3. The authors have also identified seven putative CpG islands within a 600-kb interval. Chromosomal rearrangement breakpoints -- in one Angelman syndrome (AS) patient with an unbalanced translocation and in another patient with a submicroscopic deletion -- are located within the large GABRB3 intron. These findings will facilitate chromosomal walking strategies for cloning the regions disrupted by the DNA rearrangements in these AS patients and will be valuable for mapping new genes to the AS chromosomal region. 64 refs., 6 figs., 2 tabs.

  1. The human [gamma]-aminobutyric acid receptor subunit [beta]3 and [alpha]5 gene cluster in chromosome 15q11-q13 is rich in highly polymorphic (CA)[sub n] repeats

    Energy Technology Data Exchange (ETDEWEB)

    Glatt, K.; Lalande, M. (Howard Hughes Medical Institute, Boston, MA (United States)); Sinnett, D. (Harvard Medical School, Boston, MA (United States))

    1994-01-01

    The [gamma]-aminobutyric acid (GABA[sub A]) receptor [beta]33 (GABRB3) and [alpha]5 (GABRA5) subunit genes have been localized to the Angelman and Prader-Willi syndrome region of chromosome 15q11-q13. GABRB3, which encompasses 250 kb, is located 100 kb proximal of GABRA5, with the two genes arranged in head-to-head transcriptional orientation. In screening 135 kb of cloned DNA within a 260-kb interval extending from within GABRB3 to the 5[prime] end of GABRA5, 10 new (CA), repeats have been identified. Five of these have been analyzed in detail and found to be highly polymorphic, with the polymorphism information content (PIC) ranging from 0.7 to 0.85 and with heterozygosities of 67 to 94%. In the clones from GABRB3/GABRA5 region, therefore, the frequency of (CA)[sub n] with PICs [ge] 0.7 is 1 per 27 kb. Previous estimates of the density of (CA)[sub n] with PICs [ge] 0.7 in the human genome have been approximately 10-fold lower. The GABRB3/GABRA5 region appears, therefore, to be enriched for highly informative (CA)[sub n]. This set of closely spaced, short tandem repeat polymorphisms will be useful in the molecular analyses of Prader-Willi and Angelman syndromes and in high-resolution studies of genetic recombination within this region. 21 refs., 2 figs., 1 tab.

  2. Antagonistic properties of a natural product-Bicuculline with the gamma-aminobutyric acid receptor: studied through electrostatic potential mapping, electronic and vibrational spectra using ab initio and density functional theory.

    Science.gov (United States)

    Srivastava, Anubha; Tandon, Poonam; Jain, Sudha; Asthana, B P

    2011-12-15

    (+)-Bicuculline (hereinafter referred to as bicuculline), a phthalide isoquinoline alkaloid is of current interest as an antagonist of gamma-aminobutyric acid (GABA). Its inhibitor properties have been studied through molecular electrostatic potential (MEP) mapping of this molecule and GABA receptor. The hot site on the potential surface of bicuculline, which is also isosteric with GABA receptor, has been used to interpret the inhibitor property. A systematic quantum chemical study of the possible conformations, their relative stabilities, FT-Raman, FT-IR and UV-vis spectroscopic analysis of bicuculline has been reported. The optimized geometries, wavenumber and intensity of the vibrational bands of all the conformers of bicuculline have been calculated using ab initio Hartree-Fock (HF) and density functional theory (DFT) employing B3LYP functional and 6-311G(d,p) basis set. Mulliken atomic charges, HOMO-LUMO gap ΔE, ionization potential, dipole moments and total energy have also been obtained for the optimized geometries of both the molecules. TD-DFT method is used to calculate the electronic absorption parameters in gas phase as well as in solvent environment using integral equation formalism-polarizable continuum model (IEF-PCM) employing 6-31G basis set and the results thus obtained are compared with the UV absorption spectra. The combination of experimental and calculated results provides an insight into the structural and vibrational spectroscopic properties of bicuculline. Copyright © 2011 Elsevier B.V. All rights reserved.

  3. Relationship of nocturnal concentrations of melatonin, gamma-aminobutyric acid and total antioxidants in peripheral blood with insomnia after stroke: study protocol for a prospective non-randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Wei Zhang

    2017-01-01

    Full Text Available Melatonin and gamma-aminobutyric acid (GABA have been shown to regulate sleep. The nocturnal concentrations of melatonin, GABA and total antioxidants may relate to insomnia in stroke patients. In this prospective single-center non-randomized controlled clinical trial performed in the China Rehabilitation Research Center, we analyzed the relationship of nocturnal concentrations of melatonin, GABA and total antioxidants with insomnia after stroke. Patients during rehabilitation of stroke were recruited and assigned to the insomnia group or non-insomnia group. Simultaneously, persons without stroke or insomnia served as normal controls. Each group contained 25 cases. The primary outcome was nocturnal concentrations of melatonin, GABA and total antioxidants in peripheral blood. The secondary outcomes were Pittsburgh Sleep Quality Index, Insomnia Severity Index, Epworth Sleepiness Scale, Fatigue Severity Scale, Morningness-Eveningness Questionnaire (Chinese version, and National Institute of Health Stroke Scale. The relationship of nocturnal concentrations of melatonin, GABA and total antioxidants with insomnia after stroke was analyzed and showed that they were lower in the insomnia group than in the non-insomnia group. The severity of stroke was higher in the insomnia group than in the non-insomnia group. Correlation analysis demonstrated that the nocturnal concentrations of melatonin and GABA were associated with insomnia after stroke. This trial was registered at ClinicalTrials.gov, identifier: NCT03202121.

  4. Functional modulation of cerebral gamma-aminobutyric acidA receptor/benzodiazepine receptor/chloride ion channel complex with ethyl beta-carboline-3-carboxylate: Presence of independent binding site for ethyl beta-carboline-3-carboxylate

    Energy Technology Data Exchange (ETDEWEB)

    Taguchi, J.; Kuriyama, K. (Kyoto Prefectural Univ. of Medicine (Japan))

    1990-05-01

    Effect of ethyl beta-carboline-3-carboxylate (beta-CCE) on the function of gamma-aminobutyric acid (GABA)A receptor/benzodiazepine receptor/chloride ion channel complex was studied. Beta-CCE noncompetitively and competitively inhibited (3H)flunitrazepam binding to benzodiazepine receptor, but not (3H)muscimol binding to GABAA receptor as well as t-(3H)butylbicycloorthobenzoate (( 3H) TBOB) binding to chloride ion channel, in particulate fraction of the mouse brain. Ro15-1788 also inhibited competitively (3H) flunitrazepam binding. On the other hand, the binding of beta-(3H)CCE was inhibited noncompetitively and competitively by clonazepam and competitively by Ro15-1788. In agreement with these results, benzodiazepines-stimulated (3H)muscimol binding was antagonized by beta-CCE and Ro15-1788. Gel column chromatography for the solubilized fraction from cerebral particulate fraction by 0.2% sodium deoxycholate (DOC-Na) in the presence of 1 M KCl indicated that beta-(3H)CCE binding site was eluted in the same fraction (molecular weight, 250,000) as the binding sites for (3H)flunitrazepam, (3H)muscimol and (3H)TBOB. GABA-stimulated 36Cl- influx into membrane vesicles prepared from the bovine cerebral cortex was stimulated and attenuated by flunitrazepam and beta-CCE, respectively. These effects of flunitrazepam and beta-CCE on the GABA-stimulated 36Cl- influx were antagonized by Ro15-1788. The present results suggest that the binding site for beta-CCE, which resides on GABAA receptor/benzodiazepine receptor/chloride ion channel complex, may be different from that for benzodiazepine. Possible roles of beta-CCE binding site in the allosteric inhibitions on benzodiazepine binding site as well as on the functional coupling between chloride ion channel and GABAA receptor are also suggested.

  5. (1S, 3S)-3-amino-4-difluoromethylenyl-1-cyclopentanoic acid (CPP-115), a potent gamma-aminobutyric acid aminotransferase inactivator for the treatment of cocaine addiction

    DEFF Research Database (Denmark)

    Pan, Yue; Gerasimov, Madina R; Kvist, Trine

    2012-01-01

    Vigabatrin, a GABA aminotransferase (GABA-AT) inactivator, is used to treat infantile spasms and refractory complex partial seizures and is in clinical trials to treat addiction. We evaluated a novel GABA-AT inactivator (CPP-115) and observed that it does not exhibit other GABAergic or off...... at 1/300-1/600th the dose of vigabatrin. It also blocks expression of cocaine-induced conditioned place preference at a dose 1/300th that of vigabatrin. Electroretinographic (ERG) responses in rats treated with CPP-115, at doses 20-40 times higher than those needed to treat addiction in rats, exhibited...... reductions in ERG responses, which were less than the reductions observed in rats treated with vigabatrin at the same dose needed to treat addiction in rats. In conclusion, CPP-115 can be administered at significantly lower doses than vigabatrin, which suggests a potential new treatment for addiction...

  6. Interaction of carvacrol with the Ascaris suum nicotinic acetylcholine receptors and gamma-aminobutyric acid receptors, potential mechanism of antinematodal action.

    Science.gov (United States)

    Trailović, Saša M; Marjanović, Djordje S; Nedeljković Trailović, Jelena; Robertson, Alan P; Martin, Richard J

    2015-08-01

    Essential plant oils (or their active principles) are safe to use and a potentially attractive alternative to current antiparasitic drugs. In the present study, we tested the effects of carvacrol on the isolated tissues of Ascaris suum and investigated potential interactions with other antiparasitic drugs. We used somatic muscle flaps for contraction assays, as well as for electrophysiological investigations. Carvacrol 300 μM highly significantly inhibited contractions caused by 1, 3, 10, 30, and 100 μM of ACh (p = 0.0023, p = 0.0002, p = 0.0002, p acetylcholine was 8.87 μM (log EC50 = 0.95 ± 0.26), while R max was 2.53 ± 0.24 g. The EC50 of acetylcholine in the presence of 300 μM of carvacrol was 27.71 μM (log EC50 = 1.44 ± 0.28) and the R max decreased to 1.63 ± 0.32 g. Furthermore, carvacrol highly significant potentiates inhibitory effect of GABA and piperazine on the contractions induced by ACh. However, carvacrol (100 and 300 μM), did not produce any changes in the membrane potential or conductance of the A. suum muscle cell. While, 300 μM of carvacrol showed a significant inhibitory effect on ACh-induced depolarization response. The mean control depolarization was 13.58 ± 0.66 mV and decreased in presence of carvacrol to 4.50 ± 1.02 mV (p < 0.0001). Mean control Δg was 0.168 ± 0.017 μS, while in the presence of 300 μM of carvacrol, Δg significantly decreased to 0.060 ± 0.018 ΔS (p = 0.0017). The inhibitory effect on contractions may be the explanation of the antinematodal potential of carvacrol. Moreover, inhibition of depolarizations caused by ACh and reduction of conductance changes directly points to an interaction with the nAChR in A. suum.

  7. Early continuous white noise exposure alters l-alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor subunit glutamate receptor 2 and gamma-aminobutyric acid type a receptor subunit beta3 protein expression in rat auditory cortex.

    Science.gov (United States)

    Xu, Jinghong; Yu, Liping; Zhang, Jiping; Cai, Rui; Sun, Xinde

    2010-02-15

    Auditory experience during the postnatal critical period is essential for the normal maturation of auditory function. Previous studies have shown that rearing infant rat pups under conditions of continuous moderate-level noise delayed the emergence of adult-like topographic representational order and the refinement of response selectivity in the primary auditory cortex (A1) beyond normal developmental benchmarks and indefinitely blocked the closure of a brief, critical-period window. To gain insight into the molecular mechanisms of these physiological changes after noise rearing, we studied expression of the AMPA receptor subunit GluR2 and GABA(A) receptor subunit beta3 in the auditory cortex after noise rearing. Our results show that continuous moderate-level noise rearing during the early stages of development decreases the expression levels of GluR2 and GABA(A)beta3. Furthermore, noise rearing also induced a significant decrease in the level of GABA(A) receptors relative to AMPA receptors. However, in adult rats, noise rearing did not have significant effects on GluR2 and GABA(A)beta3 expression or the ratio between the two units. These changes could have a role in the cellular mechanisms involved in the delayed maturation of auditory receptive field structure and topographic organization of A1 after noise rearing. Copyright 2009 Wiley-Liss, Inc.

  8. Quantitative Autoradiography on [(35)S]TBPS Binding Sites of Gamma- Aminobutyric Acid(A) Receptors in Discrete Brain Regions of High- Alcohol-Drinking and Low-Alcohol- Drinking Rats Selectively Bred forHigh- and Low-Alcohol Preference.

    Science.gov (United States)

    Hwang, B.H.; Kunkler, P.E.; Lumeng, L.

    1997-01-01

    It has been documented that ethanol can potentiate brain gamma-aminobutyric acid (GABA)ergic function, and there is a close link between the GABA(A) receptor complex and effects of ethanol, including reinforcement of alcohol which is a fundamental element of alcohol preference. However, it is unknown in what discrete brain regions GABA(A) receptors might be associated with alcohol preference. In the present study, [(35)S]t-butylbicyclophosphorothionate ([(35)S]TBPS) was used to localize GABA(A) receptors in high-alcohol-drinking (HAD) rats and low-alcohol-drinking (LAD) rats which were selectively bred for high and low alcohol preference, respectively. Initial qualitative observations indicated that [(35)S]TBPS binding sites were abundant in many brain areas including the cerebral cortex, hypothalamus and amygdala of HAD and LAD rats. Furthermore, the quantitative autoradiographic analysis revealed fewer [(35)S]TBPS binding sites of GABA(A) receptors in the amygdaloid complex, central medial thalamic nucleus, lateral hypothalamic nucleus and anterior hypothalamic nucleus of HAD rats than LAD rats. Collectively, this study has indicated that HAD rats selectively bred for high alcohol preference possess lower [(35)S]TBPS binding in the brain. Since lower TBPS binding has been proposed to reflect enhanced GABAergic function, as evidenced in rats with seizure or under alcohol withdrawal, the results from the present study suggest that HAD rats might have an enhanced GABAergic function. It is thus likely that enhanced GABAergic function in the brain might be related to high alcohol preference which is characteristic in HAD rats. In addition, the present result showing no difference of [(35)S]TBPS binding in the nucleus accumbens is also in agreement with a notion that [(35)S]TBPS binding may represent only a small spectrum of the GABA(A) receptor complex which is constituted of a sophisticated subunit combination whose functional compositions are still unknown. In

  9. Potentiation of cardiovascular responses to hydralazine by diverse hydrazine derivatives.

    Science.gov (United States)

    Vidrio, H

    1994-10-01

    After the observation that in anesthetized rats the antitubercular agent isoniazid potentiates the hypotensive effect of the vasodilator hydralazine (H) and transforms the accompanying reflex tachycardia to bradycardia, a number of hydrazine (HYD) derivatives were tested for this interaction in pentobarbital-anesthetized rats. All HYDs studied elicited this response in varying degrees, isoniazid, thiosemicarbazide and thiocarbohydrazide being the most active. Experiments were then carried out to explore the possibility of an influence of the HYDs on reflex reactions to H due to interaction with pyridoxal, inhibition of glutamic acid decarboxylase and decreased levels of brain gamma-aminobutyric acid. Although the H-HYDs interaction was prevented by vagotomy, it was unaffected by exogenous pyridoxal, did not occur with the alpha adrenergic antagonist prazosin and was not mimicked by non-HYD pyridoxal reactors. In other experiments, pharmacokinetic interactions and monoamine oxidase inhibition were ruled out as alternative explanations for this phenomenon. It was concluded that the H-HYDs interaction is not related to a possible influence of these drugs on central gamma-aminobutyric acid cardiovascular regulation and that other presently unknown mechanisms are involved.

  10. Gamma-aminobutyric acid-modulated benzodiazepine binding sites in bacteria

    Energy Technology Data Exchange (ETDEWEB)

    Lummis, S.C.R.; Johnston, G.A.R. (Univ. of Sydney, New South Wales (Australia)); Nicoletti, G. (Royal Melbourne Inst. of Tech. (Australia)); Holan, G. (CSIRO, Melbourne (Australia))

    1991-01-01

    Benzodiazepine binding sites, which were once considered to exist only in higher vertebrates, are here demonstrated in the bacteria E. coli. The bacterial ({sup 3}H)diazepam binding sites are modulated by GABA; the modulation is dose dependent and is reduced at high concentrations. The most potent competitors of E.Coli ({sup 3}H)diazepam binding are those that are active in displacing ({sup 3}H)benzodiazepines from vertebrate peripheral benzodiazepine binding sites. These vertebrate sites are not modulated by GABA, in contrast to vertebrate neuronal benzodiazepine binding sites. The E.coli benzodiazepine binding sites therefore differ from both classes of vertebrate benzodiazepine binding sites; however the ligand spectrum and GABA-modulatory properties of the E.coli sites are similar to those found in insects. This intermediate type of receptor in lower species suggests a precursor for at least one class of vertebrate benzodiazepine binding sites may have existed.

  11. Effects of gamma-aminobutyric acid (GABA) on synaptogenesis and synaptic function

    DEFF Research Database (Denmark)

    Belhage, B; Hansen, G H; Elster, L

    1998-01-01

    ; that is, GABA acts as a trophic signal. Accordingly, activating preexisting GABA receptors, a trophic GABA signal enhances the growth rate of neuronal processes, facilitates synapse formation, and promotes synthesis of specific proteins. Transcription and de novo synthesis are initiated by the GABA signal......, this ability to target the induced GABAA receptors is probably coupled to the maturation of neurons and not to the action of GABA per se. The induced GABAA receptors apparently mediate a pronounced inhibition of neurotransmitter release, whereas other subtypes of GABAA receptors may be modulatory rather than...

  12. Elucidating Conformational Changes in the {gamma}-Aminobutyric Acid Transporter-1

    DEFF Research Database (Denmark)

    Meinild, Anne-Kristine; Loo, Donald D F; Hansen, Søren Skovstrup

    2009-01-01

    The GABA transporter-1 (GAT-1) has three current-generating modes: GABA-coupled current, Li(+)-induced leak current, and Na(+)-dependent transient currents. We earlier hypothesized that Li(+) is able to substitute for the first Na(+) in the transport cycle and thereby induce a distinct conformation...... in GAT-1 and that the onset of the Li(+)-induced leak current at membrane potentials more negative than -50 mV was due to a voltage-dependent conformational change of the Li(+)-bound transporter. In this study, we set out to verify this hypothesis and seek insight into the structural dynamics underlying......-dependent fluorescence data obtained in sodium buffer and the associated conformational changes were distinct from those associated with the Li(+)-induced leak current. The inhibitor potency of SKF89976A of the Li(+)- versus Na(+)-bound transporter confirmed the cationic dependence of the conformational occupancy. Our...

  13. Comparison of Nootropic and Neuroprotective Features of Aryl-Substituted Analogs of Gamma-Aminobutyric Acid.

    Science.gov (United States)

    Tyurenkov, I N; Borodkina, L E; Bagmetova, V V; Berestovitskaya, V M; Vasil'eva, O S

    2016-02-01

    GABA analogs containing phenyl (phenibut) or para-chlorophenyl (baclofen) substituents demonstrated nootropic activity in a dose of 20 mg/kg: they improved passive avoidance conditioning, decelerated its natural extinction, and exerted antiamnestic effect on the models of amnesia provoked by scopolamine or electroshock. Tolyl-containing GABA analog (tolibut, 20 mg/kg) exhibited antiamnestic activity only on the model of electroshock-induced amnesia. Baclofen and, to a lesser extent, tolibut alleviated seizures provoked by electroshock, i.e. both agents exerted anticonvulsant effect. All examined GABA aryl derivatives demonstrated neuroprotective properties on the maximum electroshock model: they shortened the duration of coma and shortened the period of spontaneous motor activity recovery. In addition, these agents decreased the severity of passive avoidance amnesia and behavioral deficit in the open field test in rats exposed to electroshock. The greatest neuroprotective properties were exhibited by phenyl-containing GABA analog phenibut.

  14. Synthesis of nylon 4 from gamma-aminobutyrate (GABA) produced by recombinant Escherichia coli.

    Science.gov (United States)

    Park, Si Jae; Kim, Eun Young; Noh, Won; Oh, Young Hoon; Kim, Hye Young; Song, Bong Keun; Cho, Kwang Myung; Hong, Soon Ho; Lee, Seung Hwan; Jegal, Jonggeon

    2013-07-01

    In this study, we developed recombinant Escherichia coli strains expressing Lactococcus lactis subsp. lactis Il1403 glutamate decarboxylase (GadB) for the production of GABA from glutamate monosodium salt (MSG). Syntheses of GABA from MSG were examined by employing recombinant E. coli XL1-Blue as a whole cell biocatalyst in buffer solution. By increasing the concentration of E. coli XL1-Blue expressing GadB from the OD₆₀₀ of 2-10, the concentration and conversion yield of GABA produced from 10 g/L of MSG could be increased from 4.3 to 4.8 g/L and from 70 to 78 %, respectively. Furthermore, E. coli XL1-Blue expressing GadB highly concentrated to the OD₆₀₀ of 100 produced 76.2 g/L of GABA from 200 g/L of MSG with 62.4 % of GABA yield. Finally, nylon 4 could be synthesized by the bulk polymerization using 2-pyrrolidone that was prepared from microbially synthesized GABA by the reaction with Al₂O₃ as catalyst in toluene with the yield of 96 %.

  15. Potentiation of gamma aminobutyric acid receptors (GABAAR by Ethanol: How are inhibitory receptors affected?

    Directory of Open Access Journals (Sweden)

    Benjamin eFörstera

    2016-05-01

    Full Text Available In recent years there has been an increase in the understanding of ethanol actions on the type A -aminobutyric acid chloride channel (GABAAR, a member of the pentameric ligand gated ion channels (pLGICs. However, the mechanism by which ethanol potentiates the complex is still not fully understood and a number of publications have shown contradictory results. Thus many questions still remain unresolved requiring further studies for a better comprehension of this effect. The present review concentrates on the involvement of GABAAR in the acute actions of ethanol and specifically focuses on the immediate, direct or indirect, synaptic and extra-synaptic modulatory effects. To elaborate on the immediate, direct modulation of GABAAR by acute ethanol exposure, electrophysiological studies investigating the importance of different subunits, and data from receptor mutants will be examined. We will also discuss the nature of the putative binding sites for ethanol based on structural data obtained from other members of the pLGICs family. Finally, we will briefly highlight the glycine gated chloride channel (GlyR, another member of the pLGIC family, as a suitable target for the development of new pharmacological tools.

  16. Does gamma-aminobutyric acid (GABA influence the development of chronic inflammation in rheumatoid arthritis?

    Directory of Open Access Journals (Sweden)

    Bridges S Louis

    2008-01-01

    Full Text Available Abstract Background Recent studies have demonstrated a role for spinal p38 MAP kinase (MAPK in the development of chronic inflammation and peripheral arthritis and a role for GABA in the inhibition of p38 MAPK mediated effects. Integrating these data suggests that GABA may play a role in downregulating mechanisms that lead to the production of proinflammatory agents such as interleukin-1, interleukin-6, and matrix metalloproteinase 3 – agents implicated in the pathogenesis of rheumatoid arthritis (RA. Genetic studies have also associated RA with members of the p38 MAPK pathway. Hypothesis We propose a hypothesis for an inefficient GABA signaling system that results in unchecked proinflammatory cytokine production via the p38 MAPK pathway. This model also supports the need for increasing research in the integration of immunology and neuroscience.

  17. CHANGES IN SELECTIVITY OF GAMMA-AMINOBUTYRIC ACID FORMATION EFFECTED BY FERMENTATION CONDITIONS AND MICROORGANISMS RESOURCES

    Directory of Open Access Journals (Sweden)

    Kamila Kovalovská

    2011-10-01

    Full Text Available In this study we observe the effect of fermentation conditions and resources of microorganisms for production of γ-aminobutyric acid (GABA. The content of produced GABA depends on various conditions such as the amount of precursor, an addition of salt, enzyme and the effect of pH. The highest selectivity of GABA (74.0 % from the precursor (L-monosodium glutamate has been determinate in the follow conditions: in the presence of pre-cultured microorganisms from Encián cheese in amount 1.66 % (w/v the source of microorganisms/volume of the fermentation mixture, after the addition of 0.028 % (w/v of CaCl2/volume of the fermentation mixture, 100 μM of pyridoxal-5-phosphate (P-5-P and the GABA precursor concentration in the fermentation mixture 2.6 mg ml-1 in an atmosphere of gas nitrogen. Pure cultures of lactic acid bacteria increased the selectivity of GABA by an average of 20 % compared with bacteria from the path of Encián.

  18. EFFECT OF FOOD-MICROORGANISMS ON GAMMA-AMINOBUTYRIC ACID PRODUCTION BY FERMENTATION

    Directory of Open Access Journals (Sweden)

    Jozef Hudec

    2012-02-01

    Full Text Available Lactic acid bacteria (LAB are nice targets in order to study γ-aminobutyric acid (GABA production that has been reported to be effective in order to reduce blood pressure in experimental animals and human beings. In this study, we aimed to γ-aminobutyric acid (GABA production in aerobical and anaerobical conditions, using different sources of microorganisms. The highest selectivity of GABA from precursor L-monosodium glutamate (82.22% has been reported using of microorganisms from banana, and with addition of pyridoxal-5-phosphate (P-5-P. For augmentation of selectivity the application of the further stimulating factors of GABA biosynthesis is needed.

  19. Comparative proteomic and physiological analyses reveal the protective effect of exogenous calcium on the germinating soybean response to salt stress.

    Science.gov (United States)

    Yin, Yongqi; Yang, Runqiang; Han, Yongbin; Gu, Zhenxin

    2015-01-15

    Calcium enhances salt stress tolerance of soybeans. Nevertheless, the molecular mechanism of calcium's involvement in resistance to salt stress is unclear. A comparative proteomic approach was used to investigate protein profiles in germinating soybeans under NaCl-CaCl2 and NaCl-LaCl3 treatments. A total of 80 proteins affected by calcium in 4-day-old germinating soybean cotyledons and 71 in embryos were confidently identified. The clustering analysis showed proteins were subdivided into 5 and 6 clusters in cotyledon and embryo, respectively. Among them, proteins involved in signal transduction and energy pathways, in transportation, and in protein biosynthesis were largely enriched while those involved in proteolysis were decreased. Abundance of nucleoside diphosphate kinase and three antioxidant enzymes were visibly increased by calcium. Accumulation of gamma-aminobutyric acid and polyamines was also detected after application of exogenous calcium. This was consistent with proteomic results, which showed that proteins involved in the glutamate and methionine metabolism were mediated by calcium. Calcium could increase the salt stress tolerance of germinating soybeans via enriching signal transduction, energy pathway and transportation, promoting protein biosynthesis, inhibiting proteolysis, redistributing storage proteins, regulating protein processing in endoplasmic reticulum, enriching antioxidant enzymes and activating their activities, accumulating secondary metabolites and osmolytes, and other adaptive responses. Biological significance Soybean (Glycine max L.), as a traditional edible legume, is being targeted for designing functional foods. During soybean germination under stressful conditions especially salt stress, newly discovered functional components such as gamma-aminobutyric acid (GABA) are rapidly accumulated. However, soybean plants are relatively salt-sensitive and the growth, development and biomass of germinating soybeans are significantly

  20. Effect of gabazine on sensory stimulation train evoked response in mouse cerebellar Purkinje cells.

    Science.gov (United States)

    Bing, Yan-Hua; Jin, Wen-Zhe; Sun, Lei; Chu, Chun-Ping; Qiu, De-Lai

    2015-02-01

    Cerebellar Purkinje cells (PCs) respond to sensory stimulation via climbing fiber and mossy fiber-granule cell pathways, and generate motor-related outputs according to internal rules of integration and computation. However, the dynamic properties of sensory information processed by PC in mouse cerebellar cortex are currently unclear. In the present study, we examined the effects of the gamma-aminobutyric acid receptor A (GABA(A)) antagonist, gabazine, on the stimulation train on the simple spike firing of PCs by electrophysiological recordings method. Our data showed that the output of cerebellar PCs could be significantly affected by all pulses of the low-frequency (0.25 -2 Hz) sensory stimulation train, but only by the 1st and 2nd pulses of the high-frequency (≥ 4 Hz) sensory stimulation train. In the presence of gabazine (20 μM), each pulse of 1 Hz facial stimulation evoked simple spike firing in the PCs, but only the 1st and 2nd pulses of 4 Hz stimulation induced an increase in simple spike firing of the PCs. These results indicated that GABAA receptor-mediated inhibition did not significantly affect the frequency properties of sensory stimulation evoked responses in the mouse cerebellar PCs.

  1. Putative Neurotransmitters in ’Aplysia’: Distribution of Gamma- Aminobutyric Acid, Aspartate and Glutamate in Ganglia and Single Neurons

    Science.gov (United States)

    1975-02-01

    junction. In preliminary electrophysiological investigations, they found that while aspartate is much less effective than glutamate at depolarizing the...been described in other inver- 21 7 tebrate nervous systems. Lewis and Evans note the presence of large amounts of taurine in

  2. RP-HPLC method for simultaneous estimation of vigabatrin, gamma-aminobutyric acid and taurine in biological samples.

    Science.gov (United States)

    Police, Anitha; Shankar, Vijay Kumar; Narasimha Murthy, S

    2018-02-15

    Vigabatrin is used as first line drug in treatment of infantile spasms for its potential benefit overweighing risk of causing permanent peripheral visual field defects and retinal damage. Chronic administration of vigabatrin in rats has demonstrated these ocular events are result of GABA accumulation and depletion of taurine levels in retinal tissues. In vigabatrin clinical studies taurine plasma level is considered as biomarker for studying structure and function of retina. The analytical method is essential to monitor taurine levels along with vigabatrin and GABA. A RP-HPLC method has been developed and validated for simultaneous estimation of vigabatrin, GABA and taurine using surrogate matrix. Analytes were extracted from human plasma, rat plasma, retina and brain by simple protein precipitation method and derivatized by naphthalene 2, 3‑dicarboxaldehyde to produce stable fluorescent active isoindole derivatives. The chromatographic analysis was performed on Zorbax Eclipse AAA column using gradient elution profile and eluent was monitored using fluorescence detector. A linear plot of calibration curve was observed in concentration range of 64.6 to 6458, 51.5 to 5150 and 62.5 to 6258 ng/mL for vigabatrin, GABA and taurine, respectively with r 2  ≥ 0.997 for all analytes. The method was successfully applied for estimating levels of vigabatrin and its modulator effect on GABA and taurine levels in rat plasma, brain and retinal tissue. This RP-HPLC method can be applied in clinical and preclinical studies to explore the effect of taurine deficiency and to investigate novel approaches for alleviating vigabatrin induced ocular toxicity. Copyright © 2018. Published by Elsevier B.V.

  3. Conformational basis for the Li(+)-induced leak current in the rat gamma-aminobutyric acid (GABA) transporter-1

    DEFF Research Database (Denmark)

    MacAulay, Nanna; Zeuthen, Thomas; Gether, Ulrik

    2002-01-01

    (+)-bound conformation of the protein displayed a lower passive water permeability than that of the Na(+)- and choline (Ch(+))-bound conformations and the leak current did not saturate with increasing amounts of Li(+) in the test solution. The mechanism that gives rise to the leak current did not support active water...

  4. Buffer-free production of gamma-aminobutyric acid using an engineered glutamate decarboxylase from Escherichia coli.

    Science.gov (United States)

    Kang, Taek Jin; Ho, Ngoc Anh Thu; Pack, Seung Pil

    2013-08-15

    Escherichia coli glutamate decarboxylase (GAD) converts glutamate into γ-aminobutyric acid (GABA) through decarboxylation using proton as a co-substrate. Since GAD is active only at acidic conditions even though pH increases as the reaction proceeds, the conventional practice of using this enzyme involved the use of relatively high concentration of buffers, which might complicate the downstream purification steps. Here we show by simulation and experiments that the free acid substrate, glutamic acid, rather than its monosodium salt can act as a substrate and buffer at the same time. This yielded the buffer- and salt-free synthesis of GABA conveniently in a batch mode. Furthermore, we engineered GAD to hyper active ones by extending or reducing the length of the enzyme by just one residue at its C-terminus. Through the buffer-free reaction with engineered GAD, we could synthesize 1M GABA in 3h, which can be translated into a space-time yield of 34.3g/L/h. Copyright © 2013 Elsevier Inc. All rights reserved.

  5. GABA mediated response of aqueous, ethanol and ethyl acetate extracts of Dicranopteris linearis leaf in Swiss Albino mice

    Directory of Open Access Journals (Sweden)

    Billah Mohammad Mustakim

    2016-01-01

    Full Text Available Introduction: The objective of the study was to assess the potential of the leaf of Dicranopteris linearis in altering the CNS functions with three different extracts; aqueous, ethanol and ethyl acetate.Methods: To evaluate and compare the activities Morris maze, elevated plus maze (EPM,open field, hole cross and head dip tests were performed and many behavioral parameters wereobserved. The forced swim in Morris water maze analyzed the depression of rodents in termsof inability to self-rescue. Alongside, hole cross and open field tests assessed the inhibition oflocomotor activities. Moreover, EPM test screened the anxiolytic potential while the head dippinghole board test supported the previous experiments by evaluating both sedative, depressive andanxiolytic potentials of the extracts.Results: The results showed that the ethanol extract significantly suppressed CNS activity byreducing number of locomotor activities and increasing the stability phase (in EPM and Morrismaze supporting mild sedation, depression and anxiolysis. Furthermore, the ethyl acetate extractalso possessed moderate to high potential in reducing locomotor activities depending on gradientdoses. Results were compared with control group and found statistically significant.Conclusion: As this plant mimic the activity of a gamma-aminobutyric acid (GABA agonist, itcan be concluded that the plant may have GABA mediated involvement in central nervous system.However, the responsible compounds for these activities are yet to be investigated and this maypotentiate a new source of drug development.

  6. Cerebral radioprotection by pentobarbital: Dose-response characteristics and association with GABA agonist activity

    Energy Technology Data Exchange (ETDEWEB)

    Olson, J.J.; Friedman, R.; Orr, K.; Delaney, T.; Oldfield, E.H. (National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD (USA))

    1990-05-01

    Pentobarbital reduces cerebral radiation toxicity; however, the mechanism of this phenomenon remains unknown. As an anesthetic and depressant of cerebral metabolism, pentobarbital induces its effects on the central nervous system by stimulating the binding of gamma-aminobutyric acid (GABA) to its receptor and by inhibiting postsynaptic excitatory amino acid activity. The purpose of this study is to investigate the role of these actions as well as other aspects of the radioprotective activity of pentobarbital. Fischer 344 rats were separated into multiple groups and underwent two dose-response evaluations. In one set of experiments to examine the relationship of radioprotection to pentobarbital dose, a range of pentobarbital doses (0 to 75 mg/kg) were given intraperitoneally prior to a constant-level radiation dose (70 Gy). In a second series of experiments to determine the dose-response relationship of radiation protection to radiation dose, a range of radiation doses (10 to 90 Gy) were given with a single pentobarbital dose. Further groups of animals were used to evaluate the importance of the timing of pentobarbital administration, the function of the (+) and (-) isomers of pentobarbital, and the role of an alternative GABA agonist (diazepam). In addition, the potential protective effects of alternative methods of anesthesia (ketamine) and induction of cerebral hypometabolism (hypothermia) were examined. Enhancement of survival time from acute radiation injury due to high-dose single-fraction whole-brain irradiation was maximal with 60 mg/kg of pentobarbital, and occurred over the range of all doses examined between 30 to 90 Gy. Protection was seen only in animals that received the pentobarbital before irradiation. Administration of other compounds that enhance GABA binding (Saffan and diazepam) also significantly enhanced survival time.

  7. Cardiovascular responses to chemical stimulation of the hypothalamic arcuate nucleus in the rat: role of the hypothalamic paraventricular nucleus.

    Directory of Open Access Journals (Sweden)

    Tetsuya Kawabe

    Full Text Available The mechanism of cardiovascular responses to chemical stimulation of the hypothalamic arcuate nucleus (ARCN was studied in urethane-anesthetized adult male Wistar rats. At the baseline mean arterial pressure (BLMAP close to normal, ARCN stimulation elicited decreases in MAP and sympathetic nerve activity (SNA. The decreases in MAP elicited by ARCN stimulation were attenuated by either gamma-aminobutyric acid (GABA, neuropeptide Y (NPY, or beta-endorphin receptor blockade in the ipsilateral hypothalamic paraventricular nucleus (PVN. Combined blockade of GABA-A, NPY1 and opioid receptors in the ipsilateral PVN converted the decreases in MAP and SNA to increases in these variables. Conversion of inhibitory effects on the MAP and SNA to excitatory effects following ARCN stimulation was also observed when the BLMAP was decreased to below normal levels by an infusion of sodium nitroprusside. The pressor and tachycardic responses to ARCN stimulation at below normal BLMAP were attenuated by blockade of melanocortin 3/4 (MC3/4 receptors in the ipsilateral PVN. Unilateral blockade of GABA-A receptors in the ARCN increased the BLMAP and heart rate (HR revealing tonic inhibition of the excitatory neurons in the ARCN. ARCN stimulation elicited tachycardia regardless of the level of BLMAP. ARCN neurons projecting to the PVN were immunoreactive for glutamic acid decarboxylase 67 (GAD67, NPY, and beta-endorphin. These results indicated that: 1 at normal BLMAP, decreases in MAP and SNA induced by ARCN stimulation were mediated via GABA-A, NPY1 and opioid receptors in the PVN, 2 lowering of BLMAP converted decreases in MAP following ARCN stimulation to increases in MAP, and 3 at below normal BLMAP, increases in MAP and HR induced by ARCN stimulation were mediated via MC3/4 receptors in the PVN. These results provide a base for future studies to explore the role of ARCN in cardiovascular diseases.

  8. Cardiovascular responses to microinjections of GABA or anesthetics into the rostral ventrolateral medulla of conscious and anesthetized rats

    Directory of Open Access Journals (Sweden)

    Lacerda J.E.C.

    2003-01-01

    Full Text Available The rostral ventrolateral medulla (RVLM contains neurons involved in tonic and reflex control of arterial pressure. We describe the effects of gamma-aminobutyric acid (GABA and anesthetics injected into the RVLM of conscious and urethane (1.2 g/kg, iv anesthetized Wistar rats (300-350 g. In conscious rats, bilateral microinjection of GABA (50 nmol/200 nl induced a small but significant decrease in blood pressure (from 130 ± 3.6 to 110 ± 5.6 mmHg, N = 7. A similar response was observed with sodium pentobarbital microinjection (24 nmol/200 nl. However, in the same animals, the fall in blood pressure induced by GABA (from 121 ± 8.9 to 76 ± 8.8 mmHg, N = 7 or pentobarbital (from 118 ± 4.5 to 57 ± 11.3 mmHg, N = 6 was significantly increased after urethane anesthesia. In contrast, there was no difference between conscious (from 117 ± 4.1 to 92 ± 5.9 mmHg, N = 7 and anesthetized rats (from 123 ± 6.9 to 87 ± 8.7 mmHg, N = 7 when lidocaine (34 nmol/200 nl was microinjected into the RVLM. The heart rate variations were not consistent and only eventually reached significance in conscious or anesthetized rats. The right position of pipettes was confirmed by histology and glutamate microinjection into the RVLM. These findings suggest that in conscious animals the RVLM, in association with the other sympathetic premotor neurons, is responsible for the maintenance of sympathetic vasomotor tone during bilateral RVLM inhibition. Activity of one or more of these premotor neurons outside the RVLM can compensate for the effects of RVLM inhibition. In addition, the effects of lidocaine suggest that fibers passing through the RVLM are involved in the maintenance of blood pressure in conscious animals during RVLM inhibition.

  9. Neonatal treatment with monoamine uptake inhibitors alters later response in behavioural 'despair' test to beta and GABA-B receptor agonists.

    Science.gov (United States)

    Hilakivi, L A; Taira, T; Hilakivi, I; Loikas, P

    1988-07-01

    The administration of monoamine uptake-inhibiting antidepressant drugs to rats during the early postnatal period was previously shown to lengthen the duration of subsequent immobility in Porsolt's swim test, hence suggesting increased behavioural 'despair' in these animals. Because the mechanism of the antidepressant action may be related to changes in the cerebral monoamine or gamma-aminobutyric acid (GABA) function, the present study was carried out to examine the response in the swim test to a beta-receptor agonist salbutamol, or to the GABA-B receptor agonists progabide and baclofen in rats treated with antidepressant drugs during the second and third postnatal week: either desipramine 5 mg/kg, nomifensine 10 mg/kg or zimeldine 25 mg/kg. When tested a month later i.e. at the age of two months these rats were immobile in water for a longer period than the controls. Salbutamol 10 mg/kg and progabide 100 mg/kg increased the immobility time in the control rats but neither drug affected the rats treated with desipramine, nomifensine or zimeldine. When the animals were 5 months of age, salbutamol 10 mg/kg and baclofen 10 mg/kg shortened the immobility time in the desipramine-treated rats. The control rats and those treated with zimeldine were not affected by the drugs. The results indicate that in the rats which were neonatally treated with antidepressants, the immobility time in water is lengthened in adulthood. Moreover, the response to beta-receptor and GABA-B receptor agonists is increased from the response observed in the control rats.

  10. Brain and Serum Androsterone is Elevated in Response to Stress in Rats with Mild Traumatic Brain Injury

    Directory of Open Access Journals (Sweden)

    Richard J Servatius

    2016-08-01

    Full Text Available Exposure to lateral fluid percussion (LFP injury consistent with mild traumatic brain injury (mTBI persistently attenuates acoustic startle responses (ASRs in rats. Here, we examined whether the experience of head trauma affects stress reactivity. Male Sprague-Dawley rats were matched for ASRs and randomly assigned to receive mTBI through LFP or experience a sham surgery (SHAM. ASRs were measured post injury days (PIDs 1, 3, 7, 14, 21 and 28. To assess neurosteroids, rats received a single 2.0 mA, 0.5 s foot shock on PID 34 (S34, PID 35 (S35, on both days (2S, or the experimental context (CON. Levels of the neurosteroids pregnenolone (PREG, allopregnanolone (ALLO, and androsterone (ANDRO were determined for the prefrontal cortex, hippocampus and cerebellum. For 2S rats, repeated blood samples were obtained at 15, 30 and 60 min post-stressor for determination of corticosterone (CORT levels after stress or context on PID 34. Similar to earlier work, ASRs were severely attenuated in mTBI rats without remission for 28 days after injury. No differences were observed between mTBI and SHAM rats in basal CORT, peak CORT levels or its recovery. In serum and brain, ANDRO levels were the most stress-sensitive. Stress-induced ANDRO elevations were greater than those in mTBI rats. As a positive allosteric modulator of gamma-aminobutyric acid (GABAA receptors, increased brain ANDRO levels are expected to be anxiolytic. The impact of brain ANDRO elevations in the aftermath of mTBI on coping warrants further elaboration.

  11. Ex vivo binding of t-( sup 35 S) butylbicyclophosphorothionate: A biochemical tool to study the pharmacology of ethanol at the gamma-aminobutyric acid-coupled chloride channel

    Energy Technology Data Exchange (ETDEWEB)

    Sanna, E.; Concas, A.; Serra, M.; Santoro, G.; Biggio, G. (Univ. of Cagliari (Italy))

    1991-03-01

    The effects of acute administration of ethanol on t-(35S)Butylbiclophosphorothionate (35S-TBPS) binding measured ex vivo in unwashed membrane preparations of rat cerebral cortex were investigated. Ethanol, given i.g., decreased in a dose-related (0.5-4 g/kg) and time-dependent manner the binding of 35S-TBPS. This effect was similar to that induced by the administration of diazepam (0.5-4 mg/kg i.p.). Scatchard plot analysis of this radioligand binding revealed that ethanol, differently from diazepam, decreased the apparent affinity of 35S-TBPS recognition sites whereas it failed to change the density of these binding sites. The effect of ethanol on 35S-TBPS binding could not be reversed by the previous administration to rats of the benzodiazepine receptor antagonist, Ro 15-1788 (ethyl-8-fluoro-5,6-dihydro-5-methyl-6-oxo-4H- imidazo (1,5a) (1,4) benzodiazepine-3-carboxylate). Vice versa, the benzodiazepine receptor partial inverse agonist, Ro 15-4513 (ethyl-8-azido-5,6-dihydro-5-methyl-6-oxo-4H- imidazo (1,5a) (4,4) benzodiazepine-3-carboxylate) (8 mg/kg i.p.), prevented completely ethanol-induced decrease of 35S-TBPS binding. The ability of Ro 15-4513 to prevent the action of ethanol was shared by the anxiogenic and proconvulsant beta-carboline derivatives, FG 7142 (N-methyl-beta-carboline-3-carboxamide) (12.5 mg/kg i.p.) and ethyl-beta-carboline-3-carboxylate (0.6 mg/kg i.v.), which, per se, enhanced this parameter. Moreover, ethanol (0.5-4 g/kg) was able to reverse the increase of 35S-TBPS binding elicited by the s.c. injection of isoniazid (350 mg/kg) and to clearly attenuate the severity of tonic-clonic seizures produced by this inhibitor of the GABAergic transmission.

  12. Polyamine biosynthesis and degradation are modulated by exogenous gamma-aminobutyric acid in root-zone hypoxia-stressed melon roots.

    Science.gov (United States)

    Wang, Chunyan; Fan, Longquan; Gao, Hongbo; Wu, Xiaolei; Li, Jingrui; Lv, Guiyun; Gong, Binbin

    2014-09-01

    We detected physiological change and gene expression related to PA metabolism in melon roots under controlled and hypoxic conditions with or without 5 mM GABA. Roots with hypoxia treatment showed a significant increase in glutamate decarboxylase (GAD) activity and endogenous GABA concentration. Concurrently, PA biosynthesis and degradation accelerated with higher gene expression and enzymes activity. However, endogenous GABA concentrations showed a large and rapid increase in Hypoxia + GABA treated roots. This led to a marked increase in Glu concentration by feedback inhibition of GAD activity. Hypoxia + GABA treatment enhanced arginine (Arg), ornithine (Orn) and methionine (Met) levels, promoting enzyme gene expression levels and arginine decarboxylase (ADC), ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (SAMDC) activities in roots. Hypoxia + GABA treatment significantly increased concentrations of free putrescine (Put), spermidine (Spd) and spermine (Spm) from day two to eight, promoting the PA conversion to soluble conjugated and insoluble bound forms. However, PA degradation was significantly inhibited in hypoxia + GABA treated roots by significantly decreasing gene expression and activity of diamine oxidase (DAO) and polyamine oxidase (PAO). However, exogenous GABA showed a reduced effect in control compared with hypoxic conditions. Our data suggest that alleviating effect of exogenous GABA to hypoxia is closely associated with physiological regulation of PA metabolism. We propose a potential negative feedback mechanism of higher endogenous GABA levels from combined effects of hypoxia and exogenous GABA, which alleviate the hypoxia damage by accelerating PA biosynthesis and conversion as well as preventing PA degradation in melon plants. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  13. Effects of NaCl Replacement with Gamma-Aminobutyric acid (GABA) on the Quality Characteristics and Sensorial Properties of Model Meat Products.

    Science.gov (United States)

    Chun, Ji-Yeon; Kim, Byeongsoo; Lee, Jung Gyu; Cho, Hyung-Yong; Min, Sang-Gi; Choi, Mi-Jung

    2014-01-01

    This study investigated the effects of γ-aminobutylic acid (GABA) on the quality and sensorial properties of both the GABA/NaCl complex and model meat products. GABA/NaCl complex was prepared by spray-drying, and the surface dimensions, morphology, rheology, and saltiness were characterized. For model meat products, pork patties were prepared by replacing NaCl with GABA. For characteristics of the complex, increasing GABA concentration increased the surface dimensions of the complex. However, GABA did not affect the rheological properties of solutions containing the complex. The addition of 2% GABA exhibited significantly higher saltiness than the control (no GABA treatment). In the case of pork patties, sensory testing indicated that the addition of GABA decreased the saltiness intensity. Both the intensity of juiciness and tenderness of patties containing GABA also scored lower than the control, based on the NaCl reduction. These results were consistent with the quality characteristics (cooking loss and texture profile analysis). Nevertheless, overall acceptability of the pork patties showed that up to 1.5%, patties containing GABA did not significantly differ from the control. Consequently, the results indicated that GABA has a potential application in meat products, but also manifested a deterioration of quality by the NaCl reduction, which warrants further exploration.

  14. Residues in the extracellular loop 4 are critical for maintaining the conformational equilibrium of the gamma-aminobutyric acid transporter-1

    DEFF Research Database (Denmark)

    MacAulay, Nanna; Meinild, Anne-Kristine; Zeuthen, Thomas

    2003-01-01

    affinity, a decrease in apparent Na+ affinity, a profound shift in the Q/Vm relationship to more negative potentials, and a decreased Li+-induced leak current. The data are consistent with a shift in the conformational equilibrium of the mutant transporters, with M345H stabilized in an outward......-facing conformation and T349H in an inward-facing conformation. These data suggest that the extracellular end of transmembrane domain 7 not only undergoes conformational changes critical for the translocation process but also plays a role in regulating the conformational equilibrium between inward- and outward...

  15. Pharmacological effects of two cytolysins isolated from the sea ...

    Indian Academy of Sciences (India)

    Prakash

    2009-12-07

    ; EqTx, equinatoxin; GABA, gamma aminobutyric ..... inhibition of the acetylcholine response in a molluscan neuron when perfusing St I (0.8 μmolL–1) and St II (6.6 μmolL–1) in its native (♢) ... receptors of isolated ileum. On the ...

  16. Mutations in the GABA Transporter SLC6A1 Cause Epilepsy with Myoclonic-Atonic Seizures

    DEFF Research Database (Denmark)

    Carvill, Gemma L; McMahon, Jacinta M; Schneider, Amy

    2015-01-01

    GAT-1, encoded by SLC6A1, is one of the major gamma-aminobutyric acid (GABA) transporters in the brain and is responsible for re-uptake of GABA from the synapse. In this study, targeted resequencing of 644 individuals with epileptic encephalopathies led to the identification of six SLC6A1 mutatio...

  17. GABAA receptor γ2 subunit knockdown mice have enhanced anxiety-like behavior but unaltered hypnotic response to benzodiazepines

    Directory of Open Access Journals (Sweden)

    De Blas Angel L

    2005-04-01

    Full Text Available Abstract Background Gamma-aminobutyric acid type A receptors (GABAA-Rs are the major inhibitory receptors in the mammalian brain and are modulated by a number of sedative/hypnotic drugs including benzodiazepines and anesthetics. The significance of specific GABAA-Rs subunits with respect to behavior and in vivo drug responses is incompletely understood. The γ2 subunit is highly expressed throughout the brain. Global γ2 knockout mice are insensitive to the hypnotic effects of diazepam and die perinatally. Heterozygous γ2 global knockout mice are viable and have increased anxiety-like behaviors. To further investigate the role of the γ2 subunit in behavior and whole animal drug action, we used gene targeting to create a novel mouse line with attenuated γ2 expression, i.e., γ2 knockdown mice. Results Knockdown mice were created by inserting a neomycin resistance cassette into intron 8 of the γ2 gene. Knockdown mice, on average, showed a 65% reduction of γ2 subunit mRNA compared to controls; however γ2 gene expression was highly variable in these mice, ranging from 10–95% of normal. Immunohistochemical studies demonstrated that γ2 protein levels were also variably reduced. Pharmacological studies using autoradiography on frozen brain sections demonstrated that binding of the benzodiazepine site ligand Ro15-4513 was decreased in mutant mice compared to controls. Behaviorally, knockdown mice displayed enhanced anxiety-like behaviors on the elevated plus maze and forced novelty exploration tests. Surprisingly, mutant mice had an unaltered response to hypnotic doses of the benzodiazepine site ligands diazepam, midazolam and zolpidem as well as ethanol and pentobarbital. Lastly, we demonstrated that the γ2 knockdown mouse line can be used to create γ2 global knockout mice by crossing to a general deleter cre-expressing mouse line. Conclusion We conclude that: 1 insertion of a neomycin resistance gene into intron 8 of the γ2 gene variably

  18. Chronic baclofen therapy improves the blunted growth hormone response to intravenous arginine in subjects with spinal cord injury.

    Science.gov (United States)

    Bauman, W A; Spungen, A M; Zhong, Y G; Tsitouras, P D

    1994-05-01

    Human GH (hGH) secretion is stimulated by vigorous physical activity, whereas immobilization reduces its release. In paralyzed subjects with spinal cord injury (SCI), it has recently been shown that the release of hGH to provocative stimulation and plasma insulin-like growth factor-I (IGF-I) levels are reduced. The acute administration of baclofen, a gamma-aminobutyric acid derivative, has been shown to stimulate hGH release. The present study investigated the effect of chronic administration of baclofen on the provocative testing of hGH secretion and plasma IGF-I levels. Sixteen subjects with SCI were studied; eight subjects were treated (40-80 mg/day; > 6 months) with baclofen (Bac+), and eight were not (Bac-). Additionally, 8 non-SCI subjects were studied as controls. The groups were matched for gender and age. The subjects were not receiving any medications known to influence hGH secretion. After an overnight fast, arginine hydrochloride (30 g/subject) was infused iv over 30 min, with blood drawn for hormone determinations at baseline and 30, 60, 90, and 120 min. In the Bac- group compared with the Bac+ group, the arginine-stimulated mean plasma hGH levels at 30 and 60 min (P hGH levels (P hGH response between the Bac+ group and the control group. Plasma IGF-I levels may reflect the integrated tissue response to hGH. A significant inverse relationship was present between age and plasma IGF-I levels for the control and Bac+ groups, but not for the Bac- group. The mean plasma IGF-I level was significantly reduced in the Bac- compared with the Bac+ group. No significant differences in mean plasma IGF-I levels were noted between the Bac+ and control groups. SCI is associated with body composition changes and metabolic alterations that may be exacerbated by reduced activity of the hGH-IGF-I axis. Oral chronic baclofen therapy appears to reverse the deleterious effects of paralysis and immobilization on hGH physiology.

  19. SU-E-I-34: Intermittent Low- and High-Dose Ethanol Exposure Alters Neurochemical Responses in Adult Rat Brain: An Ex Vivo 1H NMR Spectroscopy at 11.7 T

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Do-Wan; Kim, Sang-Young; Song, Kyu-Ho; Choe, Bo-Young [Department of Biomedical Engineering, and Research Institute of Biomedical Engineering, The Catholic University of Korea College of Medicine, Seoul (Korea, Republic of)

    2014-06-01

    Purpose: The first goal of this study was to determine the influence of the dose-dependent effects of intermittent ethanol intoxication on cerebral neurochemical responses among sham controls and low- and high-dose-ethanol-exposed rats with ex vivo high-resolution spectra. The second goal of this study was to determine the correlations between the metabolite-metabolite levels (pairs-of-metabolite levels) from all of the individual data from the frontal cortex of the intermittent ethanol-intoxicated rats. Methods: Eight-week-old male Wistar rats were divided into 3 groups. Twenty rats in the LDE (n = 10) and the HDE (n = 10) groups received ethanol doses of 1.5 g/kg and 2.5 g/kg, respectively, through oral gavage every 8-h for 4 days. At the end of the 4-day intermittent ethanol exposure, one-dimensional ex vivo 500-MHz proton nuclear magnetic resonance spectra were acquired from 30 samples of the frontal cortex region (from the 3 groups). Results: Normalized total-N-acetylaspartate (tNAA: NAA + NAAG [N-acetylaspartyl-glutamate]), gamma-aminobutyric acid (GABA), and glutathione (GSH) levels were significantly lower in the frontal cortex of the HDE-exposed rats than that of the LDE-exposed rats. Moreover, compared to the CNTL group, the LDE rats exhibited significantly higher normalized GABA levels. The 6 pairs of normalized metabolite levels were positively (+) or negatively (−) correlated in the rat frontal cortex as follows: tNAA and GABA (+), tNAA and Aspartate (Asp) (−), myo-Inositol (mIns) and Asp (−), mIns and Alanine (+), mIns and Taurine (+), and mIns and tNAA (−). Conclusion: Our results suggested that repeated intermittent ethanol intoxication might result in neuronal degeneration and dysfunction, changes in the rate of GABA synthesis, and oxidative stress in the rat frontal cortex. Our ex vivo 1H high-resolution-magic angle spinning nuclear magnetic resonance spectroscopy results suggested some novel metabolic markers for the dose

  20. Gamma-aminobutyric acid and glutamic acid levels in the auditory pathway of rats with chronic tinnitus: A direct determination using high resolution point-resolved proton magnetic resonance spectroscopy (1H-MRS

    Directory of Open Access Journals (Sweden)

    Thomas J Brozoski

    2012-02-01

    Full Text Available Damage to the auditory system following high-level sound exposure reduces afferent input. Homeostatic mechanisms appear to compensate for the loss. Overcompensation may produce the sensation of sound without an objective physical correlate, i.e., tinnitus. Several potential compensatory neural processes have been identified, such as increased spontaneous activity. The cellular mechanisms enabling such compensatory processes may involve down-regulation of inhibitory neurotransmission mediated by γ-amino butyric acid (GABA, and/or up-regulation of excitatory neurotransmission, mediated by glutamic acid (Glu. Because central processing systems are integrated and well regulated, compensatory changes in one system may produce reactive changes in others. Some or all may be relevant to tinnitus. To examine the roles of GABA and Glu in tinnitus, high-resolution point resolved proton magnetic-resonance spectroscopy (1H-MRS was used to quantify their levels in the dorsal cochlear nucleus (DCN, inferior colliculus (IC, medial geniculate body( (MGB, and primary auditory cortex (A1 of rats. Chronic tinnitus was produced by a single high-level unilateral exposure to noise, and was measured using a psychophysical procedure sensitive to tinnitus. Decreased GABA levels were evident only in the MGB, with the greatest decrease, relative to unexposed controls, obtained in the contralateral MGB. Small GABA increases may have been present bilaterally in A1 and in the contralateral DCN. Although Glu levels showed considerable variation, Glu was moderately and bilaterally elevated both in the DCN and in A1. In the MGB Glu was increased ipsilaterally but decreased contralaterally. These bidirectional and region-specific alterations in GABA and Glu may reflect large-scale changes in inhibitory and excitatory equilibrium accompanying chronic tinnitus. The present results also suggest that targeting both neurotransmitter systems may be optimal in developing more effective therapeutics.

  1. SLC6A1 Mutation and Ketogenic Diet in Epilepsy With Myoclonic-Atonic Seizures.

    Science.gov (United States)

    Palmer, Samantha; Towne, Meghan C; Pearl, Phillip L; Pelletier, Renee C; Genetti, Casie A; Shi, Jiahai; Beggs, Alan H; Agrawal, Pankaj B; Brownstein, Catherine A

    2016-11-01

    Epilepsy with myoclonic-atonic seizures, also known as myoclonic-astatic epilepsy or Doose syndrome, has been recently linked to variants in the SLC6A1 gene. Epilepsy with myoclonic-atonic seizures is often refractory to antiepileptic drugs, and the ketogenic diet is known for treating medically intractable seizures, although the mechanism of action is largely unknown. We report a novel SLC6A1 variant in a patient with epilepsy with myoclonic-atonic seizures, analyze its effects, and suggest a mechanism of action for the ketogenic diet. We describe a ten-year-old girl with epilepsy with myoclonic-atonic seizures and a de novo SLC6A1 mutation who responded well to the ketogenic diet. She carried a c.491G>A mutation predicted to cause p.Cys164Tyr amino acid change, which was identified using whole exome sequencing and confirmed by Sanger sequencing. High-resolution structural modeling was used to analyze the likely effects of the mutation. The SLC6A1 gene encodes a transporter that removes gamma-aminobutyric acid from the synaptic cleft. Mutations in SLC6A1 are known to disrupt the gamma-aminobutyric acid transporter protein 1, affecting gamma-aminobutyric acid levels and causing seizures. The p.Cys164Tyr variant found in our study has not been previously reported, expanding on the variants linked to epilepsy with myoclonic-atonic seizures. A 10-year-old girl with a novel SLC6A1 mutation and epilepsy with myoclonic-atonic seizures had an excellent clinical response to the ketogenic diet. An effect of the diet on gamma-aminobutyric acid reuptake mediated by gamma-aminobutyric acid transporter protein 1 is suggested. A personalized approach to epilepsy with myoclonic-atonic seizures patients carrying SLC6A1 mutation and a relationship between epilepsy with myoclonic-atonic seizures due to SLC6A1 mutations, GABAergic drugs, and the ketogenic diet warrants further exploration. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. A randomized, open-label, standard controlled, parallel group study of efficacy and safety of baclofen, and chlordiazepoxide in uncomplicated alcohol withdrawal syndrome.

    Science.gov (United States)

    Girish, K; Vikram Reddy, K; Pandit, Lakshmi V; Pundarikaksha, H P; Vijendra, R; Vasundara, K; Manjunatha, R; Nagraj, Moulya; Shruthi, R

    2016-02-01

    Alcohol withdrawal syndrome (AWS) is a distressing condition, generally controlled by benzodiazepines (BZD's). Baclofen, a gamma-aminobutyric acid-B (GABAB) agonist, has also shown promising results in controlling AWS. As there are few studies comparing the efficacy and tolerability of chlordiazepoxide with baclofen, the present study was taken up. The objective of this study was to compare efficacy and tolerability of baclofen with chlordiazepoxide in uncomplicated AWS. Sixty subjects with uncomplicated AWS were randomized into two groups of 30 each, to receive baclofen (30 mg) or chlordiazepoxide (75 mg) in decremented fixed dose regime for 9 days. Clinical efficacy was assessed by Clinical Institute Withdrawal Assessment for Alcohol-Revised Scale (CIWA-Ar) and tolerability by the nature and severity of adverse events. Lorazepam was used as rescue medication. Secondary efficacy parameters were Clinical Global Impression scores, symptom-free days, and subject satisfaction as assessed by visual analog scale. This study was registered with Clinical Trial Registry-India (CTRI/2013/04/003588), also subsequently registered with WHO's ICTRP clinical trial portal. Both baclofen and chlordiazepoxide showed a consistent reduction in the total CIWA-Ar scores. However, chlordiazepoxide showed a faster and a more effective control of anxiety and agitation requiring lesser lorazepam supplementation, and also showed a better subject satisfaction compared to baclofen. Both the drugs showed good tolerability with mild self-limiting adverse events. The present study demonstrates that baclofen is not as good as chlordiazepoxide in the treatment of uncomplicated AWS. However, baclofen might be considered as an alternative. Copyright © 2016 Chang Gung University. Published by Elsevier B.V. All rights reserved.

  3. Cost-effectiveness analysis of baclofen and chlordiazepoxide in uncomplicated alcohol-withdrawal syndrome

    Science.gov (United States)

    Reddy, Vikram K.; Girish, K.; Lakshmi, Pandit; Vijendra, R.; Kumar, Ajay; Harsha, R.

    2014-01-01

    Objectives: Benzodiazepines (BZDs) are the first-line drugs in alcohol-withdrawal syndrome (AWS). Baclofen, a gamma-aminobutyric acidB (GABAB) agonist, controls withdrawal symptoms without causing significant adverse effects. The objective of this study was to compare the cost-effectiveness of baclofen and chlordiazepoxide in the management of uncomplicated AWS. Materials and Methods: This was a randomized, open label, standard controlled, parallel group study of cost-effectiveness analysis (CEA) of baclofen and chlordiazepoxide in 60 participants with uncomplicated AWS. Clinical efficacy was measured by the Clinical Institute Withdrawal Assessment for alcohol (CIWA-Ar) scores. Lorazepam was used as supplement medication if withdrawal symptoms could not be controlled effectively by the study drugs alone. Both direct and indirect medical costs were considered and the CEA was analyzed in both patient's perspective and third-party perspective. Results: The average cost-effectiveness ratio (ACER) in patient's perspective of baclofen and chlordiazepoxide was Rs. 5,308.61 and Rs. 2,951.95 per symptom-free day, respectively. The ACER in third-party perspective of baclofen and chlordiazepoxide was Rs. 895.01 and Rs. 476.29 per symptom-free day, respectively. Participants on chlordiazepoxide had more number of symptom-free days when compared with the baclofen group on analysis by Mann-Whitney test (U = 253.50, P = 0.03). Conclusion: Both study drugs provided relief of withdrawal symptoms. Chlordiazepoxide was more cost-effective than baclofen. Baclofen was relatively less effective and more expensive than chlordiazepoxide. PMID:25097273

  4. Specific gamma-hydroxybutyrate-binding sites but loss of pharmacological effects of gamma-hydroxybutyrate in GABA-B1-deficient mice

    DEFF Research Database (Denmark)

    Kaupmann, Klemens; Cryan, John F; Wellendorph, Petrine

    2003-01-01

    gamma-Hydroxybutyrate (GHB), a metabolite of gamma-aminobutyric acid (GABA), is proposed to function as a neurotransmitter or neuromodulator. gamma-Hydroxybutyrate and its prodrug, gamma-butyrolactone (GBL), recently received increased public attention as they emerged as popular drugs of abuse....... Altogether, these findings suggest that the GHB-induced GTPgamma[35S] responses are mediated by GABAB receptors. Following GHB or GBL application, GABAB(1)-/- mice showed neither the hypolocomotion, hypothermia, increase in striatal dopamine synthesis nor electroencephalogram delta-wave induction seen...

  5. Study on the optimal moisture adding rate of brown rice during germination by using segmented moisture conditioning method.

    Science.gov (United States)

    Cao, Yinping; Jia, Fuguo; Han, Yanlong; Liu, Yang; Zhang, Qiang

    2015-10-01

    The aim of this study was to find out the optimal moisture adding rate of brown rice during the process of germination. The process of water addition in brown rice could be divided into three stages according to different water absorption speeds in soaking process. Water was added with three different speeds in three stages to get the optimal water adding rate in the whole process of germination. Thus, the technology of segmented moisture conditioning which is a method of adding water gradually was put forward. Germinated brown rice was produced by using segmented moisture conditioning method to reduce the loss of water-soluble nutrients and was beneficial to the accumulation of gamma aminobutyric acid. The effects of once moisture adding amount in three stages on the gamma aminobutyric acid content in germinated brown rice and germination rate of brown rice were investigated by using response surface methodology. The optimum process parameters were obtained as follows: once moisture adding amount of stage I with 1.06 %/h, once moisture adding amount of stage II with 1.42 %/h and once moisture adding amount of stage III with 1.31 %/h. The germination rate under the optimum parameters was 91.33 %, which was 7.45 % higher than that of germinated brown rice produced by soaking method (84.97 %). The content of gamma aminobutyric acid in germinated brown rice under the optimum parameters was 29.03 mg/100 g, which was more than two times higher than that of germinated brown rice produced by soaking method (12.81 mg/100 g). The technology of segmented moisture conditioning has potential applications for studying many other cereals.

  6. Responsibility and Responsiveness

    DEFF Research Database (Denmark)

    Nissen, Ulrik Becker

    2011-01-01

    contemporary positions of communicative ethics, H. Richard Niebuhr’s understanding of responsibility as responsiveness, and Dietrich Bonhoeffer’s Christological concept of responsibility in a constructive dialogue with each other, the article has attempted to outline main tenets of a responsive concept...... in a differentiated unity with each other. This idea can be substantiated by a figurative appropriation of a Chalcedonian Christology, particularly the communicatio idiomatum. The communicative dimension of this concept has been found to be useful for a reinterpretation of the idea of responsibility. By engaging......The debate on the role and identity of Christian social ethics in liberal democracy touches upon the question about the relationship between universality and speci-ficity. Rather than argue for the difference between these approaches, it can be argued that they are to be understood...

  7. Stiff person syndrome and other immune-mediated movement disorders - new insights.

    Science.gov (United States)

    Balint, Bettina; Bhatia, Kailash P

    2016-08-01

    This review highlights the recent developments in immune-mediated movement disorders and how they reflect on clinical practice and our understanding of the underlying pathophysiological mechanisms. The antibody spectrum associated with stiff person syndrome and related disorders (SPSD) has broadened and, apart from the classic glutamic acid decarboxylase (GAD)- and amphiphysin-antibodies, includes now also antibodies against dipeptidyl-peptidase-like protein-6 (DPPX), gamma-aminobutyric acid type A receptor (GABAAR), glycine receptor (GlyR) and glycine transporter 2 (GlyT2). The field of movement disorders with neuronal antibodies keeps expanding with the discovery for example of antibodies against leucine rich glioma inactivated protein 1 (LGI1) and contactin associated protein 2 (Caspr2) in chorea, or antibodies targeting ARHGAP26- or Na/K ATPase alpha 3 subunit (ATP1A3) in cerebellar ataxia. Moreover, neuronal antibodies may partly account for movement disorders attributed for example to Sydenham's chorea, coeliac disease, or steroid responsive encephalopathy with thyroid antibodies. Lastly, there is an interface of immunology, genetics and neurodegeneration, e.g. in Aicardi-Goutières syndrome or the tauopathy with IgLON5-antibodies. Clinicians should be aware of new antibodies such as dipeptidyl-peptidase-like protein-6, gamma-aminobutyric acid type A receptor and glycine transporter 2 in stiff person syndrome and related disorders, as well as of the expanding spectrum of immune-mediated movement disorders.

  8. 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.

  9. Effects of surgical and chemical lesions on neurotransmitter candidates in the nucleus accumbens of the rat

    Energy Technology Data Exchange (ETDEWEB)

    Walaas, I.; Fonnum, F.

    1979-01-01

    The origin of fibers containing different neurotransmitter candidates in the nucleus accumbens of rat brain has been studied with surgical and chemical lesion techniques. Destruction of the medial forebrain bundle decreased the activity of aromatic amino acid decarboxylase by 80% in the nucleus. Cutting of the fornix or a hemitransection decreased the high affinity uptake of glutamate by 45% and the endogenous level of glutamate by 33%. The high affinity uptake of glutamate was concentrated in the synaptosomal fraction and the decrease after the lesion was most pronounced in this fraction. Restricted lesions indicated that fibers in the fimbria/fornix coming from the subiculum were responsible for this part of the glutamate uptake in the nucleus. Local injection of kainic acid into the nucleus was accompanied by a 75% decrease in choline acetyltransferase and a 35% decrease in acetylcholineserase activities, a 70% decrease in glutamate decarboxylase activity and a 60% decrease in the high affinity uptake of ..gamma..-aminobutyrate, a 45% decrease in high affinity glutamate uptake, and no change in aromatic amino acid decarboxylase activity. Performing a lesion of the fornix after kainic acid injection led to an 85% decrease in high affinity glutamate uptake, without further affecting the other neuronal markers. The results indicate that all aminergic fibers to the nucleus accumbens are ascending in the medial forebrain bundle, that the subiculum-accumbens fibers are glutamergic and the nucleus also contains intrinsic glutamergic or aspartergic cells. Cholinergic and ..gamma..-aminobutyrate-containing cells are wholly intrinsic to the nucleus.

  10. Corporate Responsibility

    DEFF Research Database (Denmark)

    Waddock, Sandra; Rasche, Andreas

    2015-01-01

    We define and discuss the concept of corporate responsibility. We suggest that corporate responsibility has some unique characteristics, which makes it different from earlier conceptions of corporate social responsibility. Our discussion further shows commonalities and differences between corporate...... responsibility and related concepts, such as corporate citizenship and business ethics. We also outline some ways in which corporations have implemented corporate responsibility in practice....

  11. Responsible drinking

    Science.gov (United States)

    Alcohol use disorder - responsible drinking; Drinking alcohol responsibly; Drinking in moderation; Alcoholism - responsible drinking ... 2016. National Institute on Alcohol Abuse and Alcoholism. Alcohol use disorder. www.niaaa.nih.gov/alcohol-health/overview-alcohol- ...

  12. Short term, low dose fluoxetine blocks estrous cycle-linked changes in responsiveness to diazepam in female rats.

    Science.gov (United States)

    Soares-Rachetti, Vanessa de P; de Sousa Pinto, Ícaro A; Santos, Raliny O; André, Eunice; Gavioli, Elaine C; Lovick, Thelma

    2016-10-01

    Anxiety behavior in female Wistar rats was assessed at different stages of the estrous cycle using the elevated plus maze (EPM). No differences were observed at any cycle stage. Pretreatment with diazepam (1 mg kg(-1) intraperitoneal (i.p.)) 30 min before testing produced an anxiolytic effect (significant increase in percentage of time in the open arms compared to control group in the same cycle phase) in animals in proestrus, estrus, and early diestrus but had no effect in rats in late diestrus. Locomotor activity (total arm entries) was unchanged at any cycle phase. When rats in the late diestrus phase were pretreated with the selective serotonin reuptake inhibitor fluoxetine (1.75 mg kg(-1) i.p. on the afternoon of early diestrus and again in the morning of late diestrus) diazepam produced an anxiolytic effect (increase percentage time in the open arms). This dose is sufficient to raise brain allopregnanolone concentration without affecting 5-hydroxytryptamine (5-HT) systems. We propose that insensitivity to diazepam in late diestrus is due to increased expression of benzodiazepine insensitive α4 subunit-containing gamma-aminobutyric acid A (GABAA) receptors triggered by a sharp decrease in brain allopregnanolone concentration. Pretreatment with fluoxetine to raise brain allopregnanolone concentration during late diestrus prevents the withdrawal effect. © The Author(s) 2016.

  13. Immune response

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/000821.htm Immune response To use the sharing features on this page, please enable JavaScript. The immune response is how your body recognizes and defends itself ...

  14. Metabolic responses of Lactobacillus plantarum strains during fermentation and storage of vegetable and fruit juices.

    Science.gov (United States)

    Filannino, P; Cardinali, G; Rizzello, C G; Buchin, S; De Angelis, M; Gobbetti, M; Di Cagno, R

    2014-04-01

    Strains of Lactobacillus plantarum were grown and stored in cherry (ChJ), pineapple (PJ), carrot (CJ), and tomato (TJ) juices to mimic the chemical composition of the respective matrices. Wheat flour hydrolysate (WFH), whey milk (W), and MRS broth were also used as representatives of other ecosystems. The growth rates and cell densities of L. plantarum strains during fermentation (24 h at 30°C) and storage (21 days at 4°C) differed only in part, being mainly influenced by the matrix. ChJ and PJ were the most stressful juices for growth and survival. Overall, the growth in juices was negatively correlated with the initial concentration of malic acid and carbohydrates. The consumption of malic acid was noticeable for all juices, but mainly during fermentation and storage of ChJ. Decreases of branched-chain amino acids (BCAA)-with the concomitant increase of their respective branched alcohols-and His and increases of Glu and gamma-aminobutyric acid (GABA) were the main traits of the catabolism of free amino acids (FAA), which were mainly evident under less acidic conditions (CJ and TJ). The increase of Tyr was found only during storage of ChJ. Some aldehydes (e.g., 3-methyl-butanal) were reduced to the corresponding alcohols (e.g., 3-methyl-1-butanol). After both fermentation and storage, acetic acid increased in all fermented juices, which implied the activation of the acetate kinase route. Diacetyl was the ketone found at the highest level, and butyric acid increased in almost all fermented juices. Data were processed through multidimensional statistical analyses. Except for CJ, the juices (mainly ChJ) seemed to induce specific metabolic traits, which differed in part among the strains. This study provided more in-depth knowledge on the metabolic mechanisms of growth and maintenance of L. plantarum in vegetable and fruit habitats, which also provided helpful information to select the most suitable starters for fermentation of targeted matrices.

  15. Sustainable responsibilities?

    DEFF Research Database (Denmark)

    Lystbæk, Christian Tang

    2015-01-01

    This working paper analyzes the conceptions of corporate responsibility for sustainable development in EU policies on CSR. The notion of corporate responsibility has until recently been limited to economical and legal responsibilities. Based on this narrow conception of corporate responsibility.......e. a combination of destruction and construction, this chapter will deconstruct conceptions of responsibility for sustainable development in these EU documents on CSR. A deconstructive conceptual analysis involves destructing dominant interpretations of a text and allowing for constructions of alternative...... such as sustainability actually means, but on what the concept says and does not say. A deconstructive analysis of EU policies on CSR, then, pinpoints that such policies are sites of conceptual struggles. This kind of analysis is suitable for studying conceptions of corporate responsibility for sustainable development...

  16. Responsible nations

    DEFF Research Database (Denmark)

    Lippert-Rasmussen, Kasper

    2009-01-01

    In National Responsibility and Global Justice, David Miller defends the view that a member of a nation can be collectively responsible for an outcome despite the fact that: (i) she did not control it; (ii) she actively opposed those of her nation's policies that produced the outcome; and (iii......) actively opposing the relevant policy was costly for her. I argue that Miller's arguments in favor of this strong externalist view about responsibility and control are insufficient. Specifically, I show that Miller's two models of synchronic collective responsibility*the like-minded group model...

  17. Competing responsibly

    NARCIS (Netherlands)

    Jeurissen, R.J.M.; Ven, van de B.W.

    2005-01-01

    In this paper we examine the effects of different competitive conditions on the determination and evaluation of strategies of corporate social responsibility (CSR). Although the mainstream of current thinking in business ethics recognizes that a firm should invest in social responsibility, the

  18. Query responses

    Directory of Open Access Journals (Sweden)

    Paweł Łupkowski

    2017-05-01

    Full Text Available In this article we consider the phenomenon of answering a query with a query. Although such answers are common, no large scale, corpus-based characterization exists, with the exception of clarification requests. After briefly reviewing different theoretical approaches on this subject, we present a corpus study of query responses in the British National Corpus and develop a taxonomy for query responses. We point at a variety of response categories that have not been formalized in previous dialogue work, particularly those relevant to adversarial interaction. We show that different response categories have significantly different rates of subsequent answer provision. We provide a formal analysis of the response categories in the framework of KoS.

  19. Renegotiating Responsibility

    DEFF Research Database (Denmark)

    Skovgaard, Jakob

    is an increasing awareness of the unintended negative side-effects associated with economic globalization. The title of the dissertation, Renegotiating Responsibility: British Anti-Apartheid Consumer Boycott Campaigns, Late 1960s to Early 1990s, accentuates the effort by the AAM to transform perceptions of what...... analysis of the campaigns is to unpack their implications for the companies’ understanding of corporate social responsibility (CSR). The drive towards a more distinct conception of CSR in the latter half of the twentieth century forms the subtext of this dissertation; implicit in this observation...... constitutes the responsibility of transnational corporations. While the targeted companies already had responsibilities towards their shareholders, the state etc., the activists sought to reinterpret and renegotiate corporate responsibilities in a socially oriented direction through interaction...

  20. Sustainable responsibilities?

    DEFF Research Database (Denmark)

    Lystbæk, Christian Tang

    2015-01-01

    , which have pervaded all areas of daily life, including the world of business. At local, national, international and global levels, policies have been formulated to encourage corporations to take responsibility for their social and environmental performance (Laszlo, 2007). In the European Union, the EU...... Commission has promoted corporate social responsibilities since 2001, first in a Green Paper (EU, 2001) and later in policies, e.g. European Alliance for CSR (EU, 2006), and strategies, e.g. Strategy 2011-2014 for Corporate Social Responsibility (EU, 2011). Drawing on Derrida´s idea of “deconstruction”, i...

  1. Response Cries.

    Science.gov (United States)

    Goffman, Erving

    1978-01-01

    Considers utterances that appear to violate the interdependence assumed by the interactionist view, entering the stream of behavior at peculiar and unnatural places, producing communicative effects but no dialogue. Self-talk, imprecations, and response cries are discussed. (EJS)

  2. Corporate responsibility

    DEFF Research Database (Denmark)

    Jensen, Karsten Klint

    2007-01-01

    of a private business; but then again, a private business would appear to be exempted from ethical responsibility. This is what Kenneth Goodpaster has called the stakeholder paradox: either we have ethics without business or we have business without ethics. Through a different route, I reach the same solution...... to this paradox as Goodpaster, namely that a corporation is the instrument of the shareholders only, but that shareholders still have an obligation to act ethically responsibly. To this, I add discussion of Friedman's claim that this responsibility consists in increasing profits. I show that most of his arguments...... fail. Only pragmatic considerations allow to a certain extent that some of the ethical responsibility is left over to democratic regulation....

  3. Mutations in the GABA Transporter SLC6A1 Cause Epilepsy with Myoclonic-Atonic Seizures

    Science.gov (United States)

    Carvill, Gemma L.; McMahon, Jacinta M.; Schneider, Amy; Zemel, Matthew; Myers, Candace T.; Saykally, Julia; Nguyen, John; Robbiano, Angela; Zara, Federico; Specchio, Nicola; Mecarelli, Oriano; Smith, Robert L.; Leventer, Richard J.; Møller, Rikke S.; Nikanorova, Marina; Dimova, Petia; Jordanova, Albena; Petrou, Steven; Helbig, Ingo; Striano, Pasquale; Weckhuysen, Sarah; Berkovic, Samuel F.; Scheffer, Ingrid E.; Mefford, Heather C.

    2015-01-01

    GAT-1, encoded by SLC6A1, is one of the major gamma-aminobutyric acid (GABA) transporters in the brain and is responsible for re-uptake of GABA from the synapse. In this study, targeted resequencing of 644 individuals with epileptic encephalopathies led to the identification of six SLC6A1 mutations in seven individuals, all of whom have epilepsy with myoclonic-atonic seizures (MAE). We describe two truncations and four missense alterations, all of which most likely lead to loss of function of GAT-1 and thus reduced GABA re-uptake from the synapse. These individuals share many of the electrophysiological properties of Gat1-deficient mice, including spontaneous spike-wave discharges. Overall, pathogenic mutations occurred in 6/160 individuals with MAE, accounting for ∼4% of unsolved MAE cases. PMID:25865495

  4. Pharmacology of nicotine: addiction, smoking-induced disease, and therapeutics.

    Science.gov (United States)

    Benowitz, Neal L

    2009-01-01

    Nicotine sustains tobacco addiction, a major cause of disability and premature death. Nicotine binds to nicotinic cholinergic receptors, facilitating neurotransmitter release and thereby mediating the complex actions of nicotine in tobacco users. Dopamine, glutamate, and gamma aminobutyric acid release are particularly important in the development of nicotine dependence, and corticotropin-releasing factor appears to contribute to nicotine withdrawal. Nicotine dependence is highly heritable. Genetic studies indicate roles for nicotinic receptor subtypes, as well as genes involved in neuroplasticity and learning, in development of dependence. Nicotine is primarily metabolized by CYP 2A6, and variability in rate of metabolism contributes to vulnerability to tobacco dependence, response to smoking cessation treatment, and lung cancer risk. Tobacco addiction is much more common in persons with mental illness and substance abuse disorders, representing a high proportion of current smokers. Pharmacotherapeutic approaches to tobacco addiction include nicotine replacement, bupropion, and varenicline, the latter a selective nicotine receptor partial agonist.

  5. Principal cell spiking, postsynaptic excitation, and oxygen consumption in the rat cerebellar cortex

    DEFF Research Database (Denmark)

    Thomsen, Kirsten; Piilgaard, Henning; Gjedde, Albert

    2009-01-01

    . In contrast, PC spiking was largely responsible for the increase in CMRO2 when ongoing neuronal activity was increased by gamma-aminobutyric acid type A receptor blockade. In this case, CMRO2 increased equally during PC spiking with excitatory synaptic activity as during PC pacemaker spiking without......One contention within the field of neuroimaging concerns the character of the depicted activity: Does it represent neuronal action potential generation (i.e., spiking) or postsynaptic excitation? This question is related to the metabolic costs of different aspects of neurosignaling. The cerebellar...... cortex is well suited for addressing this problem because synaptic input to and spiking of the principal cell, the Purkinje cell (PC), are spatially segregated. Also, PCs are pacemakers, able to generate spikes endogenously. We examined the contributions to cerebellar cortical oxygen consumption (CMRO2...

  6. Acoustic experience alters the aged auditory system.

    Science.gov (United States)

    Turner, Jeremy G; Parrish, Jennifer L; Zuiderveld, Loren; Darr, Stacy; Hughes, Larry F; Caspary, Donald M; Idrezbegovic, Esma; Canlon, Barbara

    2013-01-01

    Presbyacusis, one of the most common ailments of the elderly, is often treated with hearing aids, which serve to reintroduce some or all of those sounds lost to peripheral hearing loss. However, little is known about the underlying changes to the ear and brain as a result of such experience with sound late in life. The present study attempts to model this process by rearing aged CBA mice in an augmented acoustic environment (AAE). Aged (22-23 months) male (n = 12) and female (n = 9) CBA/CaJ mice were reared in either 6 weeks of low-level (70 dB SPL) broadband noise stimulation (AAE) or normal vivarium conditions. Changes as a function of the treatment were measured for behavior, auditory brainstem response thresholds, hair cell cochleograms, and gamma aminobutyric acid neurochemistry in the key central auditory structures of the inferior colliculus and primary auditory cortex. The AAE-exposed group was associated with sex-specific changes in cochlear pathology, auditory brainstem response thresholds, and gamma aminobutyric acid neurochemistry. Males exhibited significantly better thresholds and reduced hair cell loss (relative to controls) whereas females exhibited the opposite effect. AAE was associated with increased glutamic acid decarboxylase (GAD67) levels in the inferior colliculus of both male and female mice. However, in primary auditory cortex AAE exposure was associated with increased GAD67 labeling in females and decreased GAD67 in males. These findings suggest that exposing aged mice to a low-level AAE alters both peripheral and central properties of the auditory system and these changes partially interact with sex or the degree of hearing loss before AAE. Although direct application of these findings to hearing aid use or auditory training in aged humans would be premature, the results do begin to provide direct evidence for the underlying changes that might be occurring as a result of hearing aid use late in life. These results suggest the aged brain

  7. In Response

    Science.gov (United States)

    Egeland, Janice A.; Shaw, Jon A.; Endicott, Jean; Allen, Cleona R.; Hostetter, Abram M.

    2005-01-01

    This article features the response to the important commentary by Dr. Carlson. The Amish Study represents, as she notes, a special research population for investigation of "classic" bipolar disorder viewed against a homogeneous cultural landscape where emerging biological and behavioral prodromal features can be identified. Dr. Carlson questions…

  8. Emotional Responses

    DEFF Research Database (Denmark)

    Hansen, Flemming; Christensen, Sverre Riis; Lundsteen, Steen

    2007-01-01

    Recent neurological research has pointed to the importance of fundamental emotional processes for most kinds of human behaviour. Measures of emotional response tendencies towards brands seem to reveal intangible aspects of brand equity, particularly in a marketing context. In this paper a procedure...

  9. Responsible tourism

    Directory of Open Access Journals (Sweden)

    Birkaš E.

    2012-01-01

    Full Text Available Realising tourism in the context of responsibility is a problem of historical-social and economic time-space continuum; the problem of possibility of temporal unification of these parts. The study aims to emphasize that the essence of problem can only be understood in the depth of a general problematic of tourism, as a question of temporalisation of historical-social space, which, however, leads to a grand question of today: does the human activity which creates temporalised spaces have its own gravitational direction? Ad deliberandum. The study proposes the viewpoint that the context of responsibility requires overcoming the dimension of interpretation where the subject is understood as an ultimate human-singularity and a perfect match of responsibility with a dominant and current form of temporalisation of time suggests a paradigm of participating consciousness, the consciousness of unity, which, in Berdyaev's words, is never logical, but existential. The study, on the basis of a meticulous studying of a new narrative of tourism, primarily due to volume restrictions does not go beyond presenting the key attributes of this ever-expanding understanding of tourism - with a demonstration of a concrete practice - but all this with an emphasis that qualification of the actors' activities is possible only along the lines of a previous consideration of comprehension of structure of space and time - along the revalorisation of a motivational horison (Anzenbacher, A 1987, 264.p. and also the very term of responsibility and freedom. Responsibility can only then become an orientation of tourist activities, if the primary focus is set on re-comprehension (revalorisation of civilisational legacies in a timeless perspective.

  10. Neurotransmitters and neuronal apoptotic cell death of chronically aluminum intoxicated Nile catfish (Clarias gariepinus) in response to ascorbic acid supplementation.

    Science.gov (United States)

    Khalil, Samah R; Hussein, Mohamed M A

    2015-12-01

    Few studies have been carried out to assess the neurotoxic effect of aluminum (Al) on the aquatic creatures. This study aims to evaluate the neurotoxic effects of long term Al exposure on the Nile catfish (Clarias gariepinus) and the potential ameliorative influence of ascorbic acid (ASA) over a 180 days exposure period. Forty eight Nile catfish were divided into four groups: control group, placed in clean water, ASA exposed group (5mg/l), AlCl3 received group (28.96 μg/l; 1/20 LC50), and group received AlCl3 concomitantly with ASA. Brain tissue was examined by using flow cytometry to monitor the apoptotic cell population, HPLC analysis for the quantitative estimation of brain monoamine neurotransmitters [serotonin (5-HT), dopamine (DA), norepinephrine (NE)]. The amino acid neurotransmitters [serum taurine, glycine, aspartate and glutamine and brain gamma aminobutyric acid (GABA)] levels were assessed, plus changes in brain tissue structure using light microscopy. The concentration of Al in both brain tissue and serum was determined by using atomic absorption spectrophotometery. The Al content in serum and brain tissue were both elevated and Al exposure induced an increase in the number of apoptotic cells, a marked reduction of the monoamine and amino acids neurotransmitters levels and changes in tissue morphology. ASA supplementation partially abolished the effects of AL on the reduced neurotransmitter, the degree of apoptosis and restored the morphological changes to the brain. Overall, our results indicate that, ASA is a promising neuroprotective agent against for Al-induced neurotoxicity in the Nile catfish. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Responsive Innovation

    DEFF Research Database (Denmark)

    Pedersen, Carsten

    In dynamic environments, competitive advantage lies in developing useful knowledge from continuous streams of unstructured and ambiguous data. Frontline employees and certain groups of customers are often the first to sense emerging issues of strate-gic importance due to their experiential insights...... of the firm’s daily operations. Yet, they are rarely asked to provide updated information about critical issues. The present paper seeks to conceptually develop the notion of responsive innovation, by drawing on literary streams concerning collective sensing, strategic issue diagnosis and integra......-tive strategy within a micro foundations perspective. It is posited that companies should root their innovation processes in the collective sensing of frontline-employees and customers that operate around the organizational periphery. This frames the con-cept of responsive innovation, where individuals engaged...

  12. Responsive Innovation

    DEFF Research Database (Denmark)

    Pedersen, Carsten

    Although the importance of stakeholder networks has been recognized in recent years, a non-teleological model that incorporates their collective sensing into innovation processes has so far not been developed. Hence, this paper argues that traditional linear and sequential innovation models...... are insufficient in hypercompetitive environments. Instead, it is proposed that companies should ground their innovation processes in the collective sensing of frontline-employees and customers that operate around the organizational periphery. This frames the concept of responsive innovation, where key...

  13. Photoparoxysmal responses

    Directory of Open Access Journals (Sweden)

    Mauro Muszkat

    1990-09-01

    Full Text Available Sixty-five outpatients with photoparoxysmal response (PPR during routine EEG were studied. The PPR showed prevalence in women (75.4%. Seizures were found in 66.1% of cases. The rest recordings were abnormal in 41.8% with prevalence of generalized paroxysm. Eight patterns of PPR were observed, being polyspike mixed to slow wave the most frequent (53%. The epileptic group showed a bimodal distribution in the several bands of photic stimulation, near 8 and 20-24 Hz. A sustained paroxysmal abnormality persisting after the photic stimulation was present in 6 epileptic patients.

  14. Emotional Responses

    DEFF Research Database (Denmark)

    Hansen, Flemming; Christensen, Sverre Riis; Lundsteen, Steen

    2007-01-01

    Recent neurological research has pointed to the importance of fundamental emotional processes for most kinds of human behaviour. Measures of emotional response tendencies towards brands seem to reveal intangible aspects of brand equity, particularly in a marketing context. In this paper a procedure...... for estimating such emotional brand equity is presented and findings from two successive studies of more than 100 brands are reported. It demonstrates how changes that occur between two years are explainable in terms of factors identifiable in the markets, and that the measures otherwise are stable over time...

  15. Syntheses of {gamma}-aminobutyric-1-{sup 14}C and of {alpha}-aminoadipic-6-{sup 14}C acid from methoxy-3 chloropropyl-magnesium and marked carbon dioxide; Syntheses de l'acide {gamma}-aminobutyrique{sup 14}C-1 et de l'acide {alpha}-aminoadipique {sup 14}C-6 a partir de methoxy-3 chloropropylmagnesium et d'anhydride carbonique marque

    Energy Technology Data Exchange (ETDEWEB)

    Phung Nhu Liem [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires, Departement des radioelements, Service des molecules marquees

    1967-04-01

    Carbonation of {gamma}-methoxypropyl-magnesium chloride by CO{sub 2} gives {gamma}-methoxy-butyric carboxylic-{sup 14}C acid with a yield of about 95 per cent. When the latter is treated successively with anhydrous HBr and with diazomethane, methyl carboxylic {gamma}-bromobutyrate-{sup 14}C is formed. This in turn gives {gamma}-amino-butyric carboxylic-{sup 14}C acid with an overall yield of 66 per cent with respect to Ba{sup 14}CO{sub 3}, when it is condensed with potassium phthalimide and hydrolyzed by acid. By reacting methyl-{gamma}-bromobutyrate-{sup 14}C with the sodium derivative of ethyl cyanacetamido-acetate in ethanol, followed by an acid hydrolysis, {alpha}-aminoadipic-6-{sup 14}C acid is obtained with an overall yield of 46 per cent with respect to Ba{sup 14}CO{sub 3}. (author) [French] La carbonatation du chlorure de {gamma}-methoxypropylmagnesium par {sup 14}CO{sub 2} donne l'acide {gamma}-methoxybutyrique carboxyle {sup 14}C avec un rendement d'environ 95 pour cent. Ce dernier traite successivement par HBr anhydre et par le diazomethane conduit au {gamma}-bromobutyrate de methyle carboxyle {sup 14}C. Celui-ci condense avec le phtalimide de potassium suivi d'une hydrolyse acide fournit l'acide {gamma}-aminobutyrique carboxyle {sup 14}C avec un rendement global de 66 pour cent par rapport a Ba{sup 14}CO{sub 3}. L'action du {gamma}-bromobutyrate de methyle {sup 14}C sur le derive sode du cyanacetamidoacetate d'ethyle dans l'ethanol suivie d'hydrolyse acide donne l'acide {alpha}-aminoadipique {sup 14}C-6 avec un rendement global de 46 pour cent par rapport a Ba{sup 14}CO{sub 3}. (auteur)

  16. Responsible innovation

    CERN Document Server

    De Woot, Philippe

    2015-01-01

    Economic development is rooted in disruption, not in equilibrium. And a powerful engine of economic development is innovation; but is this innovation always for the common good? The dark side of the extraordinary dynamism of innovation lies precisely in its destructive power. If simply left to market forces, it could lead to social chaos and great human suffering. To face the challenges of our time, we must create the proper climate and culture to develop strong entrepreneurial drive. But, more than ever, we must give this entrepreneurial drive its ethical and societal dimensions. Responsible innovation means a more voluntary orientation towards the great problems of the 21st century, e.g. depletion of the planet's resources, rising inequality, and new scientific developments potentially threatening freedom, democracy and human integrity. We need to transform our ceaseless creativity into real progress for humankind. In this respect, the rapid development of social innovation opens the door for new methods an...

  17. Effects of the insecticide fipronil on reproductive endocrinology in the fathead minnow

    Science.gov (United States)

    Gamma aminobutyric acid (GABA) and GABA receptors play an important role in neuroendocrine regulation in fish. Disruption of the GABAergic system by environmental contaminants could interfere with normal regulation of the hypothalamic pituitary gonadal (HPG) axis, leading to imp...

  18. Forebrain glutamatergic, but not GABAergic, neurons mediate anxiogenic effects of the glucocorticoid receptor

    NARCIS (Netherlands)

    Hartmann, J.; Dedic, N.; Pöhlmann, M.L.; Häusl, A.; Karst, H.; Engelhardt, C.; Westerholz, S.; Wagner, K.V.; Labermaier, C.; Hoeijmakers, L.; Kertokarijo, M.; Chen, A.; Joëls, M.; Deussing, J.M.; Schmidt, M.V.

    2017-01-01

    Anxiety disorders constitute a major disease and social burden worldwide; however, many questions concerning the underlying molecular mechanisms still remain open. Besides the involvement of the major excitatory (glutamate) and inhibitory (gamma aminobutyric acid (GABA)) neurotransmitter circuits in

  19. Extraordinary arousal from semi-comatose state on zolpidem ...

    African Journals Online (AJOL)

    propylene amine oxime (99mTc HMPAO) brain single photon emission computed tomography (SPECf) before and after administration of the gamma-aminobutyric acid (GABA) agonist zolpidem. It was observed that 15 minutes after application ...

  20. Valerian

    Science.gov (United States)

    ... mechanism by which a valerian extract may cause sedation is by increasing the amount of gamma aminobutyric ... Valerian. In: Herbs for the Mind: Depression, Stress, Memory Loss, and Insomnia. New York: Guilford Press, 2000: ...

  1. Anomalous levels of Cl(-) transporters cause a decrease of GABAergic inhibition in human peritumoral epileptic cortex

    NARCIS (Netherlands)

    Conti, Luca; Palma, Eleonora; Roseti, Cristina; Lauro, Clotilde; Cipriani, Raffaela; de Groot, Marjolein; Aronica, Eleonora; Limatola, Cristina

    2011-01-01

    Purpose: Several factors contribute to epileptogenesis in patients with brain tumors, including reduced gamma-aminobutyric acid (GABA) ergic inhibition. In particular, changes in Cl(-) homeostasis in peritumoral microenvironment, together with alterations of metabolism, are key processes leading to

  2. Metabolic Responses of Lactobacillus plantarum Strains during Fermentation and Storage of Vegetable and Fruit Juices

    Science.gov (United States)

    Filannino, P.; Cardinali, G.; Rizzello, C. G.; Buchin, S.; De Angelis, M.; Gobbetti, M.

    2014-01-01

    Strains of Lactobacillus plantarum were grown and stored in cherry (ChJ), pineapple (PJ), carrot (CJ), and tomato (TJ) juices to mimic the chemical composition of the respective matrices. Wheat flour hydrolysate (WFH), whey milk (W), and MRS broth were also used as representatives of other ecosystems. The growth rates and cell densities of L. plantarum strains during fermentation (24 h at 30°C) and storage (21 days at 4°C) differed only in part, being mainly influenced by the matrix. ChJ and PJ were the most stressful juices for growth and survival. Overall, the growth in juices was negatively correlated with the initial concentration of malic acid and carbohydrates. The consumption of malic acid was noticeable for all juices, but mainly during fermentation and storage of ChJ. Decreases of branched-chain amino acids (BCAA)—with the concomitant increase of their respective branched alcohols—and His and increases of Glu and gamma-aminobutyric acid (GABA) were the main traits of the catabolism of free amino acids (FAA), which were mainly evident under less acidic conditions (CJ and TJ). The increase of Tyr was found only during storage of ChJ. Some aldehydes (e.g., 3-methyl-butanal) were reduced to the corresponding alcohols (e.g., 3-methyl-1-butanol). After both fermentation and storage, acetic acid increased in all fermented juices, which implied the activation of the acetate kinase route. Diacetyl was the ketone found at the highest level, and butyric acid increased in almost all fermented juices. Data were processed through multidimensional statistical analyses. Except for CJ, the juices (mainly ChJ) seemed to induce specific metabolic traits, which differed in part among the strains. This study provided more in-depth knowledge on the metabolic mechanisms of growth and maintenance of L. plantarum in vegetable and fruit habitats, which also provided helpful information to select the most suitable starters for fermentation of targeted matrices. PMID:24487533

  3. Technology and responsibility

    International Nuclear Information System (INIS)

    Zimmerli, W.C.

    1987-01-01

    Philosophical reflections on the concepts of responsibility and type of responsibility are presented and discussed with regard to the developments of technology. The author states that neither the relationship between liability and responsibility has changed, nor the structure of responsibility. Any individual still is responsible for his actions and their consequences. What has changed, however, is the former restriction to the concept of internal responsibility and the overlapping of acting subject and responsible subject. (DG) [de

  4. Optimal Responsible Investment

    DEFF Research Database (Denmark)

    Jessen, Pernille

    The paper studies retail Socially Responsible Investment and portfolio allocation. It extends conventional portfolio theory by allowing for a personal value based investment decision. When preferences for responsibility enter the framework for mean-variance analysis, it yields an optimal...... responsible investment model. An example of index investing illustrates the theory. Results show that it is crucial for the responsible investor to consider portfolio risk, expected return, and responsibility simultaneously in order to obtain an optimal portfolio. The model enables responsible investors...

  5. Playful Hyper Responsibility

    DEFF Research Database (Denmark)

    Knudsen, Hanne; Åkerstrøm Andersen, Niels

    2014-01-01

    . We point to a dislocation in the way parents are assigned responsibility, because the definition of responsibility is not only a question of formulating rules or providing advice. We argue that what emerges is a kind of playful hyper responsibility that identifies responsibility as the participation...

  6. Responsive web design workflow

    OpenAIRE

    LAAK, TIMO

    2013-01-01

    Responsive Web Design Workflow is a literature review about Responsive Web Design, a web standards based modern web design paradigm. The goals of this research were to define what responsive web design is, determine its importance in building modern websites and describe a workflow for responsive web design projects. Responsive web design is a paradigm to create adaptive websites, which respond to the properties of the media that is used to render them. The three key elements of responsi...

  7. Biological Responses to Materials

    Science.gov (United States)

    Anderson, James M.

    2001-08-01

    All materials intended for application in humans as biomaterials, medical devices, or prostheses undergo tissue responses when implanted into living tissue. This review first describes fundamental aspects of tissue responses to materials, which are commonly described as the tissue response continuum. These actions involve fundamental aspects of tissue responses including injury, inflammatory and wound healing responses, foreign body reactions, and fibrous encapsulation of the biomaterial, medical device, or prosthesis. The second part of this review describes the in vivo evaluation of tissue responses to biomaterials, medical devices, and prostheses to determine intended performance characteristics and safety or biocompatibility considerations. While fundamental aspects of tissue responses to materials are important from research and development perspectives, the in vivo evaluation of tissue responses to these materials is important for performance, safety, and regulatory reasons.

  8. ADDH And Methylphenidate Response

    OpenAIRE

    J Gordon Millichap

    1994-01-01

    The dose-response, clinical effectiveness, and response prediction in 76 children with ADDH treated with methylphenidate (MPH) were evaluated by a double-blind, placebo-controlled, crossover study at the Department of Psychology, University of Hawaii, Honolulu.

  9. Responsibility and Capacities

    DEFF Research Database (Denmark)

    Ryberg, Jesper

    2014-01-01

    That responsible moral agency presupposes certain mental capacities, constitutes a widely accepted view among theorists. Moreover, it is often assumed that degrees in the development of the relevant capacities co-vary with degrees of responsibility. In this article it is argued that, the move from...... the view that responsibility requires certain mental capacities to the position that degrees of responsibility co-vary with degrees of the development of the mental capacities, is premature....

  10. Playful Hyper Responsibility

    DEFF Research Database (Denmark)

    Knudsen, Hanne; Åkerstrøm Andersen, Niels

    2014-01-01

    Over the past 10–15 years, state-funded schools have begun to require parents to assume an undefined and infinite personal responsibility. In this article, we investigate how schools organize responsibility games to respond to this challenge and how these games affect the concept of responsibility...

  11. Instant responsive web design

    CERN Document Server

    Simmons, Cory

    2013-01-01

    A step-by-step tutorial approach which will teach the readers what responsive web design is and how it is used in designing a responsive web page.If you are a web-designer looking to expand your skill set by learning the quickly growing industry standard of responsive web design, this book is ideal for you. Knowledge of CSS is assumed.

  12. Aligning Responsible Business Practices

    DEFF Research Database (Denmark)

    Weller, Angeli E.

    2017-01-01

    This article offers an in-depth case study of a global high tech manufacturer that aligned its ethics and compliance, corporate social responsibility, and sustainability practices. Few large companies organize their responsible business practices this way, despite conceptual relevance and calls...... and managers interested in understanding how responsible business practices may be collectively organized....

  13. Optimal Responsible Investment

    DEFF Research Database (Denmark)

    Jessen, Pernille

    standards. This paper considers optimal responsible investment for a small retail investor. It extends conventional portfolio theory by allowing for a personal-value based investment decision. Preferences for responsibility are defined in the framework of mean-variance analysis and an optimal responsible...... investment model identified. Implications of the altered investment problem are investigated when the dynamics between portfolio risk, expected return and responsibility is considered. Relying on the definition of a responsible investor, it is shown how superior investment opportunities can emerge when...

  14. Allosteric potentiation of quisqualate receptors by a nootropic drug aniracetam.

    Science.gov (United States)

    Ito, I; Tanabe, S; Kohda, A; Sugiyama, H

    1990-05-01

    1. Allosteric potentiation of the ionotropic quisqualate (iQA) receptor by a nootropic drug aniracetam (1-p-anisoyl-2-pyrrolidinone) was investigated using Xenopus oocytes injected with rat brain mRNA and rat hippocampal slices. 2. Aniracetam potentiates the iQA responses induced in Xenopus oocytes by rat brain mRNA in a reversible manner. This effect was observed above the concentrations of 0.1 mM. Kainate. N-methyl-D-aspartate and gamma-aminobutyric acid responses induced in the same oocytes were not affected. 3. The specific potentiation of iQA responses was accompanied by an increase in the conductance change of iQA and alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) responses, but the affinity of receptors for agonist and the ion-selectivity of the channels (reversal potentials) were not changed. 4. Aniracetam reversibly potentiated the iQA responses recorded intracellularly from the pyramidal cells in the CA1 region of rat hippocampal slices. The excitatory postsynaptic potentials (EPSPs) in Schaffer collateral-commissural-CA1 synapses were also potentiated by aniracetam. 5. Population EPSPs recorded in the mossy fibre-CA3 synapses as well as Schaffer-commissural synapses were also potentiated by aniracetam. The amplitudes of the potentiation were not changed by the formation of long-term potentiation.

  15. Decoupling Responsible Management Education

    DEFF Research Database (Denmark)

    Rasche, Andreas; Gilbert, Dirk Ulrich

    Business schools increasingly aim to embed corporate responsibility, sustainability, and ethics into their curricular and extracurricular activities. This paper examines under what conditions business schools may decouple the structural effects of their engagement in responsible management educat...... education is progressing, it is also possible that an inconsistency between talk and action can help schools to articulate ambitions for responsible management education, which, over time, inspire recoupling effects....

  16. Responsibility and climate change

    OpenAIRE

    Jamieson, Dale

    2015-01-01

    Ibegin by providing some background to conceptions of responsibility. I note the extent of disagreement in this area, the diverse and cross-cutting distinctions that are deployed, and the relative neglect of some important problems. These facts make it difficult to attribute responsibility for climate change, but so do some features of climate change itself which I go on to illuminate. Attributions of responsibility are often contested sites because such attributions are fundamentally pragmat...

  17. Man - engineering - responsibility

    International Nuclear Information System (INIS)

    Tenckhoff, E.

    2000-01-01

    The mankind is growing and growing, but some live poor and some live rich on earth. Responsibility for the future when energy is consumed and fairly distributed is an intention of this article. So responsibility for availability of energy,for resource sustainability, for environment and last not least responsibility for high energy densities will be a difficult global challenge. This is clearly discussed and impressive graphically demonstrated.(GL)

  18. Environmentally Responsible Aviation Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Created in 2009 as part of NASA's Aeronautics Research Mission Directorate's Integrated Systems Research Program, the Environmentally Responsible Aviation...

  19. Biological response modifiers

    Energy Technology Data Exchange (ETDEWEB)

    Weller, R.E.

    1991-10-01

    Much of what used to be called immunotherapy is now included in the term biological response modifiers. Biological response modifiers (BRMs) are defined as those agents or approaches that modify the relationship between the tumor and host by modifying the host's biological response to tumor cells with resultant therapeutic effects.'' Most of the early work with BRMs centered around observations of spontaneous tumor regression and the association of tumor regression with concurrent bacterial infections. The BRM can modify the host response in the following ways: Increase the host's antitumor responses through augmentation and/or restoration of effector mechanisms or mediators of the host's defense or decrease the deleterious component by the host's reaction; Increase the host's defenses by the administration of natural biologics (or the synthetic derivatives thereof) as effectors or mediators of an antitumor response; Augment the host's response to modified tumor cells or vaccines, which might stimulate a greater response by the host or increase tumor-cell sensitivity to an existing response; Decrease the transformation and/or increase differentiation (maturation) of tumor cells; or Increase the ability of the host to tolerate damage by cytotoxic modalities of cancer treatment.

  20. GADRAS Detector Response Function.

    Energy Technology Data Exchange (ETDEWEB)

    Mitchell, Dean J.; Harding, Lee; Thoreson, Gregory G; Horne, Steven M.

    2014-11-01

    The Gamma Detector Response and Analysis Software (GADRAS) applies a Detector Response Function (DRF) to compute the output of gamma-ray and neutron detectors when they are exposed to radiation sources. The DRF is fundamental to the ability to perform forward calculations (i.e., computation of the response of a detector to a known source), as well as the ability to analyze spectra to deduce the types and quantities of radioactive material to which the detectors are exposed. This document describes how gamma-ray spectra are computed and the significance of response function parameters that define characteristics of particular detectors.

  1. Radiological Emergency Response Data

    Data.gov (United States)

    U.S. Environmental Protection Agency — Quality Data Asset includes all current and historical emergency radiological response event and incident of national significance data and surveillance, monitoring,...

  2. On being responsible

    DEFF Research Database (Denmark)

    Davies, Sarah Rachael; Glerup, Cecilie; Horst, Maja

    2014-01-01

    Responsible development’ has risen to become a key normative framework for nanotechnology. The technology’s governance landscape is fundamentally structured through a discourse of responsibility, in which political tools such as public engagement, voluntary reporting and soft law are mobilized so...... as to enable innovation. To call for responsibility has, indeed, become somewhat trite. In this essay we take not the normative demand for responsibility, but its operationalisation, as our analytical focus, arguing that it is important not to underestimate the term’s practical flexibility and discursive...

  3. Piracetam and fish orientation during parabolic aircraft flight

    Science.gov (United States)

    Hoffman, R. B.; Salinas, G. A.; Homick, J. L.

    1980-01-01

    Goldfish were flown in parabolic Keplerian trajectories in a KC-135 aircraft to assay both the effectiveness of piracetam as an antimotion sickness drug and the effectiveness of state-dependent training during periods of oscillating gravity levels. Single-frame analyses of infrared films were performed for two classes of responses - role rates in hypogravity or hypogravity orienting responses (LGR) and climbing responses in hypergravity or hypergravity orienting responses (HGR). In Experiment I, preflight training with the vestibular stressor facilitated suppression of LGR by the 10th parabola. An inverse correlation was found between the magnitudes of LGR and HGR. Piracetam was not effective in a state-dependent design, but the drug did significantly increase HGR when injected into trained fish shortly before flight. In Experiment II, injections of saline, piracetam, and modifiers of gamma-aminobutyric acid - aminooxyacetic acid (AOAA) and isonicotinic acid did not modify LGR. AOAA did significantly increase HGR. Thus, the preflight training has a beneficial effect in reducing disorientation in the fish in weightlessness, but the drugs employed were ineffective.

  4. Responsible geographies and geographies of response

    DEFF Research Database (Denmark)

    Grindsted, Thomas Skou

    and responsibilities concerning academic fights over representing global environmental change. A major part concerns the theoretical basis and draws inspiration from a series of critical geographical work on the marketization of universities, and relates this tincture to the wider education for sustainability...... in higher education literature. The methodological framework is based on the social nature approach that tangles these quite distinct epistemological communities by consulting the socio-natures produced. It is concluded that though geographers find sustainability themes important to geography...

  5. Collective Responsibility for Oppression

    NARCIS (Netherlands)

    Stahl, Titus

    2017-01-01

    Many contemporary forms of oppression are not primarily the result of formally organized collective action nor are they an unintended outcome of a combination of individual actions. This raises the question of collective responsibility. I argue that we can only determine who is responsible for

  6. Oil Spill Response Manual

    NARCIS (Netherlands)

    Marieke Zeinstra; Sandra Heins; Wierd Koops

    2014-01-01

    A two year programme has been carried out by the NHL University of Applied Sciences together with private companies in the field of oil and chemical spill response to finalize these manuals on oil and chemical spill response. These manuals give a good overview of all aspects of oil and chemical

  7. Neuroimaging and Responsibility Assessments

    NARCIS (Netherlands)

    Vincent, N.A.

    2009-01-01

    Could neuroimaging evidence help us to assess the degree of a person’s responsibility for a crime which we know that they committed? This essay defends an affirmative answer to this question. A range of standard objections to this high-tech approach to assessing people’s responsibility is considered

  8. Responsible Hospitality. Prevention Updates

    Science.gov (United States)

    Colthurst, Tom

    2004-01-01

    Responsible Hospitality (RH)--also called Responsible Beverage Service (RBS)--encompasses a variety of strategies for reducing risks associated with the sale and service of alcoholic beverages. RH programs have three goals: (1) to prevent illegal alcohol service to minors; (2) to reduce the likelihood of drinkers becoming intoxicated; and (3) to…

  9. Electrodermal Response in Gaming

    Directory of Open Access Journals (Sweden)

    J. Christopher Westland

    2011-01-01

    Full Text Available Steady improvements in technologies that measure human emotional response offer new possibilities for making computer games more immersive. This paper reviews the history of designs a particular branch of affective technologies that acquire electrodermal response readings from human subjects. Electrodermal response meters have gone through continual improvements to better measure these nervous responses, but still fall short of the capabilities of today's technology. Electrodermal response traditionally have been labor intensive. Protocols and transcription of subject responses were recorded on separate documents, forcing constant shifts of attention between scripts, electrodermal measuring devices and of observations and subject responses. These problems can be resolved by collecting more information and integrating it in a computer interface that is, by adding relevant sensors in addition to the basic electrodermal resistance reading to untangle (1 body resistance; (2 skin resistance; (3 grip movements; other (4 factors affecting the neural processing for regulation of the body. A device that solves these problems is presented and discussed. It is argued that the electrodermal response datastreams can be enriched through the use of added sensors and a digital acquisition and processing of information, which should further experimentation and use of the technology.

  10. Eastern Frequency Response Study

    Energy Technology Data Exchange (ETDEWEB)

    Miller, N.W.; Shao, M.; Pajic, S.; D' Aquila, R.

    2013-05-01

    This study was specifically designed to investigate the frequency response of the Eastern Interconnection that results from large loss-of-generation events of the type targeted by the North American Electric Reliability Corp. Standard BAL-003 Frequency Response and Frequency Bias Setting (NERC 2012a), under possible future system conditions with high levels of wind generation.

  11. Response Surface Methodology

    NARCIS (Netherlands)

    Kleijnen, Jack P.C.

    2014-01-01

    Abstract: This chapter first summarizes Response Surface Methodology (RSM), which started with Box and Wilson’s article in 1951 on RSM for real, non-simulated systems. RSM is a stepwise heuristic that uses first-order polynomials to approximate the response surface locally. An estimated polynomial

  12. Response surface methodolgy

    NARCIS (Netherlands)

    Kleijnen, J.P.C.; Fu, Michael C.

    2015-01-01

    This chapter first summarizes Response Surface Methodology (RSM), which started with Box and Wilson’s 1951 article on RSM for real, non-simulated systems. RSM is a stepwise heuristic that uses first-order polynomials to approximate the response surface locally. An estimated polynomial metamodel

  13. UN assesses tsunami response

    Directory of Open Access Journals (Sweden)

    Marion Couldrey

    2005-07-01

    Full Text Available A report to the UN’s Economic and Social Council (ECOSOC identifies lessons learned from the humanitarian response. Recommendations stress the need for national ownership and leadership of disaster response and recovery, improved coordination, transparent use of resources, civil society engagement and greater emphasis on risk reduction.

  14. [Social responsibility of surgeons].

    Science.gov (United States)

    Gu, Jin

    2012-01-01

    Surgeon is sacred career. To cure patients by surgery is the surgeon's work, while the social responsibility is the surgeon's soul. To strengthen and promote the social responsibility is a demand of our age; thus, every surgeon should adhere to the supremacy of the patients' interests in clinical practice.

  15. Indicators of responsible investing

    NARCIS (Netherlands)

    Scholtens, Bert

    Responsible investment has witnessed significant changes in the past decade. It is estimated that about one fifth of assets under management in the US and about half of all assets under management in the EU are done on the basis of one of the seven responsible investment strategies. This paper

  16. Predictors of maternal responsiveness.

    Science.gov (United States)

    Drake, Emily E; Humenick, Sharron S; Amankwaa, Linda; Younger, Janet; Roux, Gayle

    2007-01-01

    To explore maternal responsiveness in the first 2 to 4 months after delivery and to evaluate potential predictors of maternal responsiveness, including infant feeding, maternal characteristics, and demographic factors such as age, socioeconomic status, and educational level. A cross-sectional survey design was used to assess the variables of maternal responsiveness, feeding patterns, and maternal characteristics in a convenience sample of 177 mothers in the first 2 to 4 months after delivery. The 60-item self-report instrument included scales to measure maternal responsiveness, self-esteem, and satisfaction with life as well as infant feeding questions and sociodemographic items. An online data-collection strategy was used, resulting in participants from 41 U.S. states. Multiple regression analysis showed that satisfaction with life, self-esteem, and number of children, but not breastfeeding, explained a significant portion of the variance in self-reported maternal responsiveness scores. In this analysis, sociodemographic variables such as age, education, income, and work status showed little or no relationship to maternal responsiveness scores. This study provides additional information about patterns of maternal behavior in the transition to motherhood and some of the variables that influence that transition. Satisfaction with life was a new predictor of maternal responsiveness. However, with only 15% of the variance explained by the predictors in this study, a large portion of the variance in maternal responsiveness remains unexplained. Further research in this area is needed.

  17. UN assesses tsunami response

    OpenAIRE

    Marion Couldrey; Tim Morris

    2005-01-01

    A report to the UN’s Economic and Social Council (ECOSOC) identifies lessons learned from the humanitarian response. Recommendations stress the need for national ownership and leadership of disaster response and recovery, improved coordination, transparent use of resources, civil society engagement and greater emphasis on risk reduction.

  18. Response model parameter linking

    NARCIS (Netherlands)

    Barrett, M.L.D.

    2015-01-01

    With a few exceptions, the problem of linking item response model parameters from different item calibrations has been conceptualized as an instance of the problem of equating observed scores on different test forms. This thesis argues, however, that the use of item response models does not require

  19. Responsive Space Program Brief

    Energy Technology Data Exchange (ETDEWEB)

    Dors, Eric E. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2014-03-11

    The goal of the Responsive Space program is to make significant, integrated science and technology contributions to the end-to-end missions of the U.S. Government that protect against global emerging and nuclear threats, from the earliest adversary planning through resilient event response report describes the LANL space program, mission, and other activities. The report describes some of their activities.

  20. The price of responsibility

    DEFF Research Database (Denmark)

    Gjerris, Mickey; Gamborg, Christian; Röcklinsberg, H.

    2011-01-01

    This paper examines the challenges that climate change raises for animal agriculture and discusses the contributions that may come from a virtue ethics based approach. Two scenarios of the future role of animals in farming are set forth and discussed in terms of their ethical implications. The pa...... such as attentiveness, responsibility, competence, and responsiveness as central elements in any mitigation or adaptation program....

  1. Antipsychotic and sedative effects of the leaf extract of Crassocephalum bauchiense (Hutch.) Milne-Redh (Asteraceae) in rodents.

    Science.gov (United States)

    Sotoing Taïwe, Germain; Ngo Bum, Elisabeth; Talla, Emmanuel; Dawe, Amadou; Okomolo Moto, Fleur Clarisse; Temkou Ngoupaye, Gwladys; Sidiki, Neteydji; Dabole, Bernard; Djomeni Dzeufiet, Paul Désiré; Dimo, Théophile; De Waard, Michel

    2012-08-30

    Crassocephalum bauchiense (Hutch.) Milne-Redh (Asteraceae) has been used as a medicine for the treatment of epilepsy, insomnia, dementia and psychotic disorders in Cameroonian traditional medicine. This study was designed to examine whether the aqueous extract and the alkaloid fraction prepared from the leaves of Crassocephalum bauchiense possess antipsychotic and sedative properties in rodents. The rectal temperature of mice was recorded with a probe thermometer at a constant depth. Novelty-induced rearing behavior is used to evaluate a central excitatory locomotor behavior in mice. The antipsychotic effects of the extracts were assessed using the apomorphine animal model of psychosis. The catalepsy test was tested based on the ability of the leaves extracts of Crassocephalum bauchiense to alter the duration of akinesia by placing the naive mice with both forelegs over a horizontal bar. The extracts of Crassocephalum bauchiense effects were evaluated on sodium pentobarbital-induced sleeping time. In addition, gamma-aminobutyric acid concentrations in the brain treated mice were also estimated. The aqueous extract and the alkaloid fraction from Crassocephalum bauchiense caused dose-dependent inhibition of novelty-induced rearing behavior, decreased the apomorphine-induced stereotypy and fighting, and had significant fall of the body temperature. The aqueous extract prolonged the sodium pentobarbital sleeping time. This prolongation was not reversed by bicuculline, a light-sensitive competitive antagonist of GABA(A) receptors complex. However, the effect of the aqueous extract on sodium pentobarbital-induced sleeping time was blocked by N-methyl-β-carboline-3-carboxamide, a partial inverse agonist of the benzodiazepine site in the GABA(A) receptor complex and flumazenil, a specific antagonist of the benzodiazepine site in the GABAA receptor complex. In biochemical experiments, the concentration of the inhibitory amino acid, gamma-aminobutyric acid, was

  2. Oil spill response plan

    International Nuclear Information System (INIS)

    1999-08-01

    The plan outlined in this document specifies the actions that the Canadian Wildlife Service Atlantic Region is mandated to take in the event of an oil spill, or on discovering oiled migratory birds in terrestrial, fresh water, marine and inter-tidal habitats. In addition to describing the role and responsibilities of the Canadian Wildlife Service, the document also describes response plans of other agencies for dealing with all wildlife species affected by oil spills. Reporting paths, the lead agency concept, shared responsibilities with other Canadian Wildlife Service regional offices, provincial agencies, Heritage Canada, non-government wildlife response agencies, oil spill response organizations, and international organizations are outlined. An overview of the reporting and communications process is also provided

  3. Science's social responsibility

    DEFF Research Database (Denmark)

    Sandvik, Kjetil

    2014-01-01

    like Science in the City in which the science institutions communicate and discuss science with interested citizens. It can be done in relation to strategic plans: solving medical, environmental, socio-political problems for which the state or commercial actors provide funding. But it can also be what......What is science’s social responsibility? Is it like corporate responsibility an add-on to the main product: we produce knowledge and scientific solutions, but we also care for the environment, for sustainability, for fair-trade and so on? Or doesn’t social responsibility add to science at all...... solving problems and thus creating a base for science in its strategic mode, in its interplay-with-society mode. So science’s social responsibility may utter itself in various ways but I think it is fair to say that it is all about responsibility for taking part in making society move forward...

  4. Progressive Response Surfaces

    Science.gov (United States)

    Romero, V. J.; Swiler, L. P.

    2004-01-01

    Response surface functions are often used as simple and inexpensive replacements for computationally expensive computer models that simulate the behavior of a complex system over some parameter space. Progressive response surfaces are ones that are built up progressively as global information is added from new sample points in the parameter space. As the response surfaces are globally upgraded based on new information, heuristic indications of the convergence of the response surface approximation to the exact (fitted) function can be inferred. Sampling points can be incrementally added in a structured fashion, or in an unstructured fashion. Whatever the approach, at least in early stages of sampling it is usually desirable to sample the entire parameter space uniformly. At later stages of sampling, depending on the nature of the quantity being resolved, it may be desirable to continue sampling uniformly over the entire parameter space (Progressive response surfaces), or to switch to a focusing/economizing strategy of preferentially sampling certain regions of the parameter space based on information gained in early stages of sampling (Adaptive response surfaces). Here we consider Progressive response surfaces where a balanced indication of global response over the parameter space is desired.We use a variant of Moving Least Squares to fit and interpolate structured and unstructured point sets over the parameter space. On a 2-D test problem we compare response surface accuracy for three incremental sampling methods: Progressive Lattice Sampling; Simple-Random Monte Carlo; and Halton Quasi-Monte-Carlo sequences. We are ultimately after a system for constructing efficiently upgradable response surface approximations with reliable error estimates.

  5. Geospatial Information Response Team

    Science.gov (United States)

    Witt, Emitt C.

    2010-01-01

    Extreme emergency events of national significance that include manmade and natural disasters seem to have become more frequent during the past two decades. The Nation is becoming more resilient to these emergencies through better preparedness, reduced duplication, and establishing better communications so every response and recovery effort saves lives and mitigates the long-term social and economic impacts on the Nation. The National Response Framework (NRF) (http://www.fema.gov/NRF) was developed to provide the guiding principles that enable all response partners to prepare for and provide a unified national response to disasters and emergencies. The NRF provides five key principles for better preparation, coordination, and response: 1) engaged partnerships, 2) a tiered response, 3) scalable, flexible, and adaptable operations, 4) unity of effort, and 5) readiness to act. The NRF also describes how communities, tribes, States, Federal Government, privatesector, and non-governmental partners apply these principles for a coordinated, effective national response. The U.S. Geological Survey (USGS) has adopted the NRF doctrine by establishing several earth-sciences, discipline-level teams to ensure that USGS science, data, and individual expertise are readily available during emergencies. The Geospatial Information Response Team (GIRT) is one of these teams. The USGS established the GIRT to facilitate the effective collection, storage, and dissemination of geospatial data information and products during an emergency. The GIRT ensures that timely geospatial data are available for use by emergency responders, land and resource managers, and for scientific analysis. In an emergency and response capacity, the GIRT is responsible for establishing procedures for geospatial data acquisition, processing, and archiving; discovery, access, and delivery of data; anticipating geospatial needs; and providing coordinated products and services utilizing the USGS' exceptional pool of

  6. Frequency Response Analysis Tool

    Energy Technology Data Exchange (ETDEWEB)

    Etingov, Pavel V. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Kosterev, Dmitry [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Dai, T. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2014-12-01

    Frequency response has received a lot of attention in recent years at the national level, which culminated in the development and approval of North American Electricity Reliability Corporation (NERC) BAL-003-1 Frequency Response and Frequency Bias Setting Reliability Standard. This report is prepared to describe the details of the work conducted by Pacific Northwest National Laboratory (PNNL) in collaboration with the Bonneville Power Administration and Western Electricity Coordinating Council (WECC) Joint Synchronized Information Subcommittee (JSIS) to develop a frequency response analysis tool (FRAT). The document provides the details on the methodology and main features of the FRAT. The tool manages the database of under-frequency events and calculates the frequency response baseline. Frequency response calculations are consistent with frequency response measure (FRM) in NERC BAL-003-1 for an interconnection and balancing authority. The FRAT can use both phasor measurement unit (PMU) data, where available, and supervisory control and data acquisition (SCADA) data. The tool is also capable of automatically generating NERC Frequency Response Survey (FRS) forms required by BAL-003-1 Standard.

  7. Nucleus Accumbens and Its Role in Reward and Emotional Circuitry: A Potential Hot Mess in Substance Use and Emotional Disorders

    Directory of Open Access Journals (Sweden)

    Mani Pavuluri

    2017-04-01

    Full Text Available Nucleus accumbens (NAc is a key region in the brain that is integral to both the reward and the emotional systems. The aim of the current paper is to synthesize the basic and the clinical neuroscience discoveries relevant to the NAc for the purpose of two-way translation. Selected literature on the structure and the functionality of the NAc is reviewed across animal and human studies. Dopamine, gamma-aminobutyric acid (GABA and glutamate are the three key neurotransmitters that modulate the reward function and the motor activity. Dissociative roles of the core and the shell of the NAc include getting to the reward and staying on task with discretion, respectively. NAc shows decreased activation to reward in the individuals with major depressive disorder and the bipolar disorder, relative to that healthy controls (HC. The “difficult to please” or insatiability in response to reward in the emotional disorders may possibly be explained by such a neural pattern. Furthermore, it is likely that the increased amygdala activity reported in mood disorders could be accentuating the “wanting” of the reward by the virtue of its connections with the NAc, explaining the potential “hot mess”. In contrast, the NAc shows increased reward response in substance use disorders, relative to HC, in response to reward and emotional tasks. Accurate characterization of the NAc and its functionality in the human imaging studies of mood and substance use has important treatment implications.

  8. Emergency response strategies

    International Nuclear Information System (INIS)

    Carrilo, D.; Dias de la Cruz, F.

    1984-01-01

    In the present study is estimated, on the basis of a release category (PWR4) and several accident scenarios previously set up, the emergency response efficacy obtained in the application of different response strategies on each of the above mentioned scenarios. The studied strategies contemplate the following protective measures: evacuation, shelter and relocation. The radiological response has been obtained by means of CRAC2 (Calculation of Reactor Accident Consequences) code, and calculated in terms of absorbed dose equivalent (Whole body and thyroid), as well as early and latent biological effects. (author)

  9. Responses to the contributors

    Directory of Open Access Journals (Sweden)

    Garrett Barden

    2011-09-01

    Full Text Available A set of responses to the papers on Garrett Barden's and Tim Murphy's book Law and Justice in Community (Oxford: OUP, 2010 published in this special issue of Nordicum-Mediterraneum.

  10. Canada's Response to Refugees.

    Science.gov (United States)

    Lanphier, C. Michael

    1981-01-01

    Traces the types and numbers of refugees to Canada since World War II. Reviews key developments in Canadian refugee policy and practices before discussing the nation's response to the current refugee situation. (Author/MK)

  11. Human response to vibration

    National Research Council Canada - National Science Library

    Mansfield, Neil J

    2005-01-01

    .... Vibration measurements and standards are also addressed. This book meets the needs of those requiring knowledge of human response to vibration in order to make practical improvements to physical working environments...

  12. Responsive design high performance

    CERN Document Server

    Els, Dewald

    2015-01-01

    This book is ideal for developers who have experience in developing websites or possess minor knowledge of how responsive websites work. No experience of high-level website development or performance tweaking is required.

  13. The EEG Photoparoxysmal Response

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2008-03-01

    Full Text Available Types of photosensitivity, prevalence and other characteristics of the photoparoxysmal response (PPR, associated seizures, effect of video games, and drug therapy are reviewed by the director of electroencephalography at the University of Illinois, Chicago.

  14. Deltamethrin Petition and Response

    Science.gov (United States)

    FIFRA exclusive use provisions for minor use registrations provide incentives to pesticide companies to register minor uses of pesticides. View petitions for exclusive use periods or extensions and EPA responses.

  15. Socially responsible investment engagement

    NARCIS (Netherlands)

    Goessling, T.; Buijter, Bas; Freeman, R.E.; Kujala, J.; Sachs, S.

    2017-01-01

    This study explores engagement in socially responsible investment (SRI) processes. More specifically, it researches the impact of shareholder salience on the success of engagement activities. The research question asks: What is the relationship between shareholder salience and engagement effort

  16. Decoupling Responsible Management Education

    DEFF Research Database (Denmark)

    Rasche, Andreas; Gilbert, Dirk Ulrich

    stringency, (2) face overt or covert resistance against change processes, (3) are confronted with competing institutional pressures, and (4) perceive institutional demands as ambiguous. The discussion points to two implications. While decoupling may give rise to the illusion that responsible management...... education from organizational practices. We argue that schools may be unable to match rising institutional pressures to publicly commit to responsible management education with their internal capacity for change. Our analysis proposes that decoupling is likely if schools (1) are exposed to resource......Business schools increasingly aim to embed corporate responsibility, sustainability, and ethics into their curricular and extracurricular activities. This paper examines under what conditions business schools may decouple the structural effects of their engagement in responsible management...

  17. Environmental Response Team

    Science.gov (United States)

    This website will serve as a resource directory of the Environmental Response Team's roles and capabilities as well as list contacts for each discipline to provide information to EPA personnel and the public.

  18. Regional Response Teams

    Science.gov (United States)

    There are thirteen in the U.S., each representing a geographic region (including the Caribbean and the Pacific Basin). Composed of representatives from field offices of the agencies that make up the National Response Team, and state representatives.

  19. OEM Emergency Response Information

    Data.gov (United States)

    U.S. Environmental Protection Agency — The Office of Emergency Management retains records of all incident responses in which it participates. This data asset includes three major sources of information:...

  20. Scientific Social Responsibility?

    DEFF Research Database (Denmark)

    Glerup, Cecilie; Horst, Maja

    for the development of competitive knowledge economies. In the present paper, these developments are all understood as moves to increase the social responsibility of science, i.e. efforts to hold science accountable to wider social, economic and ethical values. Despite the widespread political and theoretical plea...... formed organizations to make science responsible for its social effects. More recently, ideals of increasing the social acceptability of science through engagement, reflexivity and dialogue seems to have found their way into the heart of policy-making, not least as a way of making science a prime motor...... for scientific social responsibility (SSR), however, there is a striking lack of knowledge about how it should be (or indeed is) performed in practice. This paper makes a first step in this direction by mapping different interpretations of what scientific social responsibility might entail. It also charts...

  1. NOAA Emergency Response Imagery

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The imagery posted on this site is in response to natural disasters. The aerial photography missions were conducted by the NOAA Remote Sensing Division. The majority...

  2. Immune responses to metastases

    International Nuclear Information System (INIS)

    Herberman, R.B.; Wiltrout, R.H.; Gorelik, E.

    1987-01-01

    The authors present the changes in the immune system in tumor-bearing hosts that may influence the development of progression of metastases. Included are mononuclear cell infiltration of metastases; alterations in natural resistance mediated by natural killer cells and macrophages; development of specific immunity mediated by T-lymphocytes or antibodies; modulation of tumor-associated antigen expression; and the down-regulation of the immune response to the tumor by several suppressor mechanisms; the augmentation of the immune response and its potential for therapeutic application; includes the prophylaxis of metastases formation by NK cells; the therapy of metastases by augmentation NK-, macrophage-, or T-lymphocyte-mediated responses by biological response modifiers; and the transfer of anticancer activity by cytoxic T-lymphocytes or immunoconjugates of monoclonal antibodies with specificity for tumors

  3. Social Responsibility of Accounting

    OpenAIRE

    JINNAI, Yoshiaki

    2011-01-01

    Historical and theoretical inquiries into the function of accounting have provided fruitful insights into social responsibility of accounting, which is, and should be, based on accounts kept through everyday accounting activities. However, at the current stage of capitalist accounting, keeping accounts is often regarded as merely a preparatory process for creating financial statements at the end of an accounting period. Thus, discussions on the social responsibility of accounting tend to conc...

  4. Advances in Crash Response

    Centers for Disease Control (CDC) Podcasts

    2009-06-29

    In this podcast, Dr. Richard C. Hunt, Director of CDC's Division of Injury Response, provides an overview on the benefits of using an Advanced Automatic Collision Notification system, or AACN, to help with emergency triage of people injured in vehicle crashes.  Created: 6/29/2009 by National Center for Injury Prevention and Control (NCIPC), Division of Injury Response (DIR).   Date Released: 6/29/2009.

  5. Responsability of nuclear industry

    International Nuclear Information System (INIS)

    Cadiz Deleito, J.C.

    1985-01-01

    Since the beginning of nuclear industry, civil responsibility with damages to the public health and properties was a critical problem, because the special conditions of this industry (nuclear accident, damages could be very high but probability of these events is very low). Legal precepts, universally accepted, in the first 60 years for all countries interested in nuclear energy are being revised, then 20 years of experience. The civil responsibility limited is being questioned and indemnities updated. (author)

  6. Social responsibility of corporations

    Directory of Open Access Journals (Sweden)

    Babić Jovan

    2007-01-01

    Full Text Available The issue at stake in the article is corporate social responsibility. There are two rival theories regarding this issue. According to the classical theory managers are responsible to owners (stockholders and their obligation is to pursue the goal of maximizing the profit. According to the other, stakeholder theory, the interests of all corporate stakeholders, all those affected by business, not only stockholders, must be taken in consideration. In the paper these two theories are subject of thorough ethical analysis.

  7. Discord of response

    Science.gov (United States)

    Roga, W.; Giampaolo, S. M.; Illuminati, F.

    2014-09-01

    The presence of quantum correlations in a quantum state is related to the state's response to local unitary perturbations. Such a response is quantified by the distance between the unperturbed and perturbed states, minimized with respect to suitably identified sets of local unitary operations. In order to be a bona fide measure of quantum correlations, the distance function must be chosen among those that are contractive under completely positive and trace preserving (CPTP) maps. The most relevant instances of such physically well-behaved metrics include the trace, the Bures, and the Hellinger distance. To each of these metrics one can associate the corresponding discord of response, namely the trace, or Hellinger, or Bures minimum distance from the set of unitarily perturbed states. All these three discords of response satisfy the basic axioms for a proper measure of quantum correlations. In the present work we focus in particular on the Bures distance, which enjoys the unique property of being both Riemannian and contractive under CPTP maps, and admits important operational interpretations in terms of state distinguishability. We compute analytically the Bures discord of response for two-qubit states with maximally mixed marginals and we compare it with the corresponding Bures geometric discord, namely the geometric measure of quantum correlations defined as the Bures distance from the set of classical-quantum states. Finally, we investigate and identify the maximally quantum correlated two-qubit states according to the Bures discord of response. These states exhibit a remarkable nonlinear dependence on the global state purity.

  8. Enviromental responsability and corporate social responsability

    Directory of Open Access Journals (Sweden)

    Jesús Marí Farinós

    2015-12-01

    Full Text Available The environmental management of companies and organizations in general is going to be internalized in the operation and management structures, linking conceptual and chronologically to improve corporate reputation, management excellence, knowledge and innovation. Embracing, undoubtedly too, with the assumption of an ethical commitment of the company to society: environmental sustainability and generational solidarity in the transmission of culture and values of that nature. The existing need to know the potential impact of business operations on society and the environment results in the appearance of a document, which may well be called a Sustainability Report or Social Balance, which is compiled from a series social indicators, which are the instruments responsible to reflect the value of the shares held by the company in social and environmental fields.

  9. Muscarinic Long-Term Enhancement of Tonic and Phasic GABAA Inhibition in Rat CA1 Pyramidal Neurons

    Science.gov (United States)

    Domínguez, Soledad; Fernández de Sevilla, David; Buño, Washington

    2016-01-01

    Acetylcholine (ACh) regulates network operation in the hippocampus by controlling excitation and inhibition in rat CA1 pyramidal neurons (PCs), the latter through gamma-aminobutyric acid type-A receptors (GABAARs). Although, the enhancing effects of ACh on GABAARs have been reported (Dominguez et al., 2014, 2015), its role in regulating tonic GABAA inhibition has not been explored in depth. Therefore, we aimed at determining the effects of the activation of ACh receptors on responses mediated by synaptic and extrasynaptic GABAARs. Here, we show that under blockade of ionotropic glutamate receptors ACh, acting through muscarinic type 1 receptors, paired with post-synaptic depolarization induced a long-term enhancement of tonic GABAA currents (tGABAA) and puff-evoked GABAA currents (pGABAA). ACh combined with depolarization also potentiated IPSCs (i.e., phasic inhibition) in the same PCs, without signs of interactions of synaptic responses with pGABAA and tGABAA, suggesting the contribution of two different GABAA receptor pools. The long-term enhancement of GABAA currents and IPSCs reduced the excitability of PCs, possibly regulating plasticity and learning in behaving animals. PMID:27833531

  10. Meige`s syndrome associated with basal ganglia and thalamic functional disorders

    Energy Technology Data Exchange (ETDEWEB)

    Sakai, Tsutomu; Shikishima, Keigo; Kawai, Kazushige; Kitahara, Kenji [Jikei Univ., Tokyo (Japan). School of Medicine

    1998-11-01

    Magnetic resonance imaging (MRI) or single positron emission computed tomography (SPECT) or both were performed and the responses of surface electromyography (EMG) were examined in seven cases of Meige`s syndrome. MRI or SPECT or both demonstrated lesions of the basal ganglia, the thalamus, or both in five of the cases. Surface EMG revealed abnormal burst discharges in the orbicularis oculi and a failure of reciprocal muscular activity between the frontalis and orbicularis oculi in all the cases. These findings suggest that voluntary motor control and reciprocal activity in the basal ganglia-thalamocortical circuits are impaired in Meige`s syndrome. In addition, good responses were seen to clonazepam, tiapride and trihexyphenidyl in these cases. Therefore, we conclude that dopaminergic, cholinergic, and {gamma}-aminobutyric acid (GABA) ergic imbalances in the disorders of the basal ganglia and thalamus in Meige`s syndrome cause control in the excitatory and inhibitory pathways to be lost, resulting in the failure of integration in reciprocal muscular activity and voluntary motor control. This failure subsequently causes the symptoms of Meige`s syndrome. (author)

  11. Newer N-phthaloyl GABA derivatives with antiallodynic and antihyperalgesic activities in both sciatic nerve and spinal nerve ligation models of neuropathic pain.

    Science.gov (United States)

    Yogeeswari, Perumal; Ragavendran, Jegadeesan Vaigunda; Sriram, Dharmarajan; Kavya, Ramkumar; Vanitha, Kaliappan; Neelakantan, Harshini

    2008-01-01

    There is considerable research evidence supporting a palliative role for gamma-aminobutyric acid (GABA)-ergic neurotransmission and voltage-gated sodium channel blockade in neuropathic pain conditions. Hence, the present study was undertaken to assess the peripheral analgesic, antiallodynic and antihyperalgesic activities of the synthesized structural analogues of GABA. The screening study included acute tissue injury, chronic constriction injury (CCI), and spinal nerve ligation (SNL) models of neuropathic pain. All of the tested compounds sup-pressed the acetic acid-induced writhing response significantly in comparison to the control. In particular, compound JVP-8 was observed to be the most active compound with percent inhibition greater than that of the standard drug aspirin (97.8% inhibition of writhing response as against 97.0% shown by aspirin). In neuropathic pain studies, compound JVP-5 (100 mg/kg i.p.) emerged as the most active compound affording maximum protection against dynamic allodynia and mechanical hyperalgesia in the CCI model, and against spontaneous pain and mechanical hyperalgesia in SNL rats. In this study, we have demonstrated that combining phthalimide pharmacophore with GABA has evolved compounds effective for the treatment of neuropathic pain. (c) 2008 S. Karger AG, Basel.

  12. Enhancement of hydralazine hypotension by low doses of isoniazid. Possible role of semicarbazide-sensitive amine oxidase inhibition.

    Science.gov (United States)

    Vidrio, H; Medina, M; Fernandez, G; Lorenzana-Jimenez, M; Campos, A E

    2000-10-01

    The influence of pretreatment with 1 through 300 mg/kg ip of isoniazid (ISO) on blood pressure and heart rate responses to 0.1 mg/kg iv of hydralazine (HYD) was assessed in rats anesthetized with chloralose--urethane. HYD hypotension was significantly enhanced by ISO at doses between 3 and 300 mg/kg ip. Heart rate was not influenced by HYD in control or pretreated animals. Depressor responses to 0.2 mg/kg iv of pinacidil (PIN) were also potentiated by ISO at 100 and 300, but not at 30 mg/kg. Similarly, ISO decreased cerebral gamma-aminobutyric acid (GABA) at the two highest doses; 30 mg/kg was without effect. Pretreatment of rats with ISO at 1 through 300 mg/kg failed to influence HYD-induced relaxation of aortic rings. These results were interpreted as indicating that potentiation of HYD hypotension by high doses of ISO is not specific for that vasodilator and is related to decreased cerebral GABA, as postulated previously. Lower doses could specifically potentiate the HYD-induced hypotensive effect by inhibition of semicarbazide-sensitive amine oxidase (SSAO), since both ISO and HYD are potent inhibitors of this enzyme. In support of this hypothesis, the SSAO inhibitors, benserazide (100 mg/kg ip) and mexiletine (50 mg/kg ip), were also found to enhance HYD hypotension.

  13. Effects of the benzodiazepine receptor antagonist flumazenil in hepatic encephalopathy in humans.

    Science.gov (United States)

    Bansky, G; Meier, P J; Riederer, E; Walser, H; Ziegler, W H; Schmid, M

    1989-09-01

    If increased gamma-aminobutyric acid (GABA)-mediated neurotransmission contributes to the mediation of hepatic encephalopathy, it may be possible to induce ameliorations of the syndrome by pharmacologically antagonizing a component of the GABA/benzodiazepine receptor complex. To test this possibility we administered the benzodiazepine receptor antagonist flumazenil by intravenous injection to 14 patients with hepatic encephalopathy complicating cirrhosis. Flumazenil administration induced variable and transient, but distinct, improvements of the mental status in 71% of the patients. The degree of encephalopathy improved from stage IV to stage II in 4 patients and from stage IV to stage III in 2 patients. The mental status of all patients with less advanced encephalopathy (3 with stage III, 1 with stage II) also improved, but these responses were clinically less impressive. The arousal effect occurred within minutes after the injection and lasted for 1 to 2 h. Furthermore, it was associated with a significant increase of the mean electroencephalographic frequency from 4.2 to 5.2 cycle/s. Of the 8 patients who were ultimately discharged from the hospital, 7 had responded to flumazenil. No patient who died within 48 h of receiving flumazenil had shown any arousal effect. These findings strongly favor a prominent pathogenetic role of increased GABAergic tone in hepatic encephalopathy in humans and suggest that a positive response to flumazenil might be of prognostic value in predicting short-term survival in encephalopathic patients with liver disease.

  14. The Role of the Medial Prefrontal Cortex-Amygdala Circuit in Stress Effects on the Extinction of Fear

    Directory of Open Access Journals (Sweden)

    Mouna Maroun

    2007-01-01

    Full Text Available Stress exposure, depending on its intensity and duration, affects cognition and learning in an adaptive or maladaptive manner. Studies addressing the effects of stress on cognitive processes have mainly focused on conditioned fear, since it is suggested that fear-motivated learning lies at the root of affective and anxiety disorders. Inhibition of fear-motivated response can be accomplished by experimental extinction of the fearful response to the fear-inducing stimulus. Converging evidence indicates that extinction of fear memory requires plasticity in both the medial prefrontal cortex and the amygdala. These brain areas are also deeply involved in mediating the effects of exposure to stress on memory. Moreover, extensive evidence indicates that gamma-aminobutyric acid (GABA transmission plays a primary role in the modulation of behavioral sequelae resulting from a stressful experience, and may also partially mediate inhibitory learning during extinction. In this review, we present evidence that exposure to a stressful experience may impair fear extinction and the possible involvement of the GABA system. Impairment of fear extinction learning is particularly important as it may predispose some individuals to the development of posttraumatic stress disorder. We further discuss a possible dysfunction in the medial prefrontal cortex-amygdala circuit following a stressful experience that may explain the impaired extinction caused by exposure to a stressor.

  15. The responsibility to protect.

    Science.gov (United States)

    Deutscher, Matt

    2005-01-01

    The decision whether, if ever, to intervene in the affairs of a sovereign state with military force has become a critical issue of the post Cold War era. In 2000 the Canadian government launched the International Commission on Intervention and State Sovereignty (ICISS), which in 2001 published its findings in The Responsibility to Protect. The Commission found broad support for the notion of sovereignty not only as a right, but also a responsibility, the responsibility of a state to provide protection for its people. The primary responsibility for protecting citizens rests with states. But when states are unable or unwilling to provide this protection, or are themselves the perpetrators of atrocities, the Commission argues that the international community has a responsibility temporarily to step in, forcefully if necessary. The Commission resisted the temptation to identify human rights violations falling short of outright killing or ethnic cleansing. This eliminates the possibility of intervening on the basis of systematic oppression of human rights or intervening to remove a military dictatorship. The intention of the report was to provoke debate; to strengthen the role of the United Nations and ensure that such interventions were multilateral and meeting the wider needs of a region and not the interests of major powers. There is an ongoing need to ensure that the Security Council is effective and that resources match the political will. These debates must continue within a UN framework.

  16. Structural building response review

    International Nuclear Information System (INIS)

    1980-01-01

    The integrity of a nuclear power plant during a postulated seismic event is required to protect the public against radiation. Therefore, a detailed set of seismic analyses of various structures and equipment is performed while designing a nuclear power plant. This report describes the structural response analysis method, including the structural model, soil-structure interaction as it relates to structural models, methods for seismic structural analysis, numerical integration methods, methods for non-seismic response analysis approaches for various response combinations, structural damping values, nonlinear response, uncertainties in structural properties, and structural response analysis using random properties. The report describes the state-of-the-art in these areas for nuclear power plants. It also details the past studies made at Sargent and Lundy to evaluate different alternatives and the conclusions reached for the specific purposes that those studies were intended. These results were incorporated here because they fall into the general scope of this report. The scope of the present task does not include performing new calculations

  17. Drones and Responsibility

    DEFF Research Database (Denmark)

    How does the use of military drones affect the legal, political, and moral responsibility of different actors involved in their deployment and design? This volume offers a fresh contribution to the ethics of drone warfare by providing, for the first time, a systematic interdisciplinary discussion...... our conception of agency and responsibility. The book will be of interest to scholars and students in (military) ethics and to those in law, politics and the military involved in the design, deployment and evaluation of military drones.......How does the use of military drones affect the legal, political, and moral responsibility of different actors involved in their deployment and design? This volume offers a fresh contribution to the ethics of drone warfare by providing, for the first time, a systematic interdisciplinary discussion...... of different responsibility issues raised by military drones. The book discusses four main sets of questions: First, from a legal point of view, we analyse the ways in which the use of drones makes the attribution of criminal responsibility to individuals for war crimes more complicated and what adjustments...

  18. Corporate responses to stakeholder activism

    DEFF Research Database (Denmark)

    Uldam, Julie; Krause Hansen, Hans

    2017-01-01

    Corporations are increasingly expected to act responsibly. The purpose of this paper is to examine two types of corporate responses to these expectations: overt and covert responses. Specifically, it examines oil companies’ involvement in multi-stakeholder initiatives and sponsorships (overt...... responses) and their monitoring of critics, including non-governmental organisations (NGOs) and activist organisations (covert responses)....

  19. When Immediate Responses Fail

    DEFF Research Database (Denmark)

    Dothan, Shai

    2018-01-01

    Tit-for-tat is a strategy of immediate and proportional responses. Game theorists showed that this strategy often leads to fruitful cooperation. Indeed, many legal regimes resemble a tit-for-tat strategy and benefit from its ability to avoid unnecessary conflicts. But in situations of uncertainty...... a disproportionately forceful response. The laws of war, criminal law, and international sales law all face some situations of uncertainty. This paper argues that each of these legal fields adopts a strategy of many-tits-for-many-tats to address conditions of acute uncertainty.......-strikes. When uncertainty prevails, a strategy of many-tits-for-many-tats is optimal. Actors applying this strategy study the actions of their adversary over multiple rounds without issuing an immediate response. Only when the actor is convinced that the adversary intentionally defects, the actor will issue...

  20. Responsibility and evil imagination.

    Science.gov (United States)

    Lamothe, R

    1995-09-01

    In this Niebuhrian perspective on hostile and violent discourse the author utilizes H. R. Niebuhr's fourfold notion of responsibility and his concept of evil imagination to examine relations marred by protracted hostility toward hated "other" or "others." The author argues that violent and hostile discourse manifests a particular form of responsibility whereby persons expressing hostility toward hated "others" construct, by way of negative representations, maligned histories and identities for the "other" and at the same time construct an idealized or glorified history and identity for themselves. These positive and negative representations and histories, then, are utilized to answer questions regarding interpretation, accountability, and solidarity. Niebuhr's concept of evil imagination is employed to hypothesize about the intransigence of this form of responsibility and to suggest reasons why elevated and maligned representations, identities, and histories are, more often than not, inextricably and tragically linked.

  1. Disaster mitigation: initial response.

    Science.gov (United States)

    Kennedy, George; Richards, Michael; Chicarelli, Michael; Ernst, Amy; Harrell, Andrew; Stites, Danniel

    2013-01-01

    The objective of this review is to stimulate the reader's considerations for developing community disaster mitigation. Disaster mitigation begins long before impact and is defined as the actions taken by a community to eliminate or minimize the impact of a disaster. The assessment of vulnerabilities, the development of infrastructure, memoranda of understanding, and planning for a sustainable response and recovery are parts of the process. Empowering leadership and citizens with knowledge of available resources through the planning and development of a disaster response can strengthen a community's resilience, which can only add to the viability and quality of life enjoyed by the entire community.

  2. Radiation response of tumours

    International Nuclear Information System (INIS)

    Twentyman, P.R.

    1988-01-01

    In this chapter knowledge regarding cellular radiation response and the factors which modify it is related to the volume changes and probability of control of irradiated solid tumors. After a discussion of the different cell populations present within solid tumors the cell population kinetics of the neoplastic cells are considered in more detail. The influence of factors related to the three-dimensional geometry of the tumor, particularly hypoxia, are considered, and also the role of the tumor vasculature in radiation response. Repair of sublethal damage (SLD) and potentially lethal damage (PLD) is dealt with and finally the relationship between the various end-points of tumor radioresponsiveness is discussed

  3. Whistleblowing & Professional Responsibilities.

    Science.gov (United States)

    Professional Engineer, 1979

    1979-01-01

    Discussed are the moral dilemmas encountered daily by professionals and how the teaching of ethics may help resolve the conflicts individuals face with respect to whistleblowing. Included are consideration of responsibilities, role of ethics codes, and courses on professional ethics. (CS)

  4. Response to Mackenzie

    Science.gov (United States)

    Peers, Chris

    2014-01-01

    Chris Peers begins his response to Jim Mackenzie's article, "Peers on Socrates and Plato" by asking "What is the 'masculine imaginary?'" Peers defines the term "imaginary" as it is applied in his article, "Freud, Plato and Irigaray: A Morpho-Logic of Teaching and Learning" (2012) and draws…

  5. Reader Response Makes History.

    Science.gov (United States)

    Shafer, Gregory

    1997-01-01

    Describes an interdisciplinary unit that brought the Civil War to life for 11th-grade students in a team-taught unit that highlighted student-driven response to reading. Describes use of a 19th-century essay supporting slavery, Upton Sinclair's "The Jungle,""Huckleberry Finn," Civil War poetry and other writings, and student projects based on the…

  6. Response to Tom Cobb

    Science.gov (United States)

    Nation, Paul

    2016-01-01

    In this article Paul Nation responds to Thomas Cobb's "Numbers or Numerology? A Response to Nation (2014) and McQuillan (2016)" (EJ1117024). Nation begins by clarifying his own position on vocabulary learning and goes on to highlight points made in Cobb's article with which he is in agreement, while drawing from his 2014 article,…

  7. Developing Responsible Learners

    Science.gov (United States)

    Gautum, Satyen; Jangam, Sachin; Loh, Kai Chee

    2018-01-01

    Developing responsible learners is one of the key education challenges of our time. Education literature suggests that for students to see themselves as active and necessary participants in their own learning, it is important that they view themselves as stakeholders in education. This research aims at exploring the effectiveness of instructional…

  8. Energy-responsive timekeeping

    Indian Academy of Sciences (India)

    2016-08-26

    Aug 26, 2016 ... ... regulators of metabolism, and are directly responsive to cellular energy supply. This close interaction is likely to be critical for normal circadian regulation of metabolism, and may also underlie the disruption of proper metabolic rhythms observed in metabolic disorders, such as obesity and type-II diabetes.

  9. Individual heat stress response

    NARCIS (Netherlands)

    Havenith, G.

    1997-01-01

    In 5 experiments, heterogeneous subject groups (large variations in _VO2 max, regular daily activity level, mass, body surface area (AD), % body fat, and AD/mass ratio) were tested for their physiological response while exercising on a cycle ergometer at a relative (45% _VO2 max; REL) or an absolute

  10. Response to Hoover.

    Science.gov (United States)

    Burket, George R.

    1984-01-01

    The developer of the Comprehensive Tests of Basic Skills scaling responds to Hoover's attacks on Thurstone and item response theory scales (TM 510 173). While agreeing that grade equivalent (GE) scores are presently the most appropriate developmental score for reporting elementary grade achievement tests, limitations and inconsistencies in the GE…

  11. Aesthetic responses to music

    DEFF Research Database (Denmark)

    Istok, Eva; Brattico, Elvira; Jacobsen, Thomas

    2009-01-01

    We explored the content and structure of the cognitive, knowledge-based concept underlying aesthetic responses to music. To this aim, we asked 290 Finnish students to verbally associate the aesthetic value of music and to write down a list of appropriate adjectives within a given time limit. No m...

  12. Corporate social responsibility

    Directory of Open Access Journals (Sweden)

    Arsić Zoran

    2011-01-01

    Full Text Available Corporate Social Responsibility (CSR is a concept whereby companies integrate social and environmental concerns in their business operations and in their interaction with their stakeholders on a voluntary basis. Definition emphasizes three basic characteristics of CSR. CSR is voluntary concept, it covers environmental issues and interaction with stakeholders, not only shareholders, is taken into account.

  13. Critical Response Protocol

    Science.gov (United States)

    Ellingson, Charlene; Roehrig, Gillian; Bakkum, Kris; Dubinsky, Janet M.

    2016-01-01

    This article introduces the Critical Response Protocol (CRP), an arts-based technique that engages students in equitable critical discourse and aligns with the "Next Generation Science Standards" vision for providing students opportunities for language learning while advancing science learning (NGSS Lead States 2013). CRP helps teachers…

  14. Overcoming the "Run" Response

    Science.gov (United States)

    Swanson, Patricia E.

    2013-01-01

    Recent research suggests that it is not simply experiencing anxiety that affects mathematics performance but also how one responds to and regulates that anxiety (Lyons and Beilock 2011). Most people have faced mathematics problems that have triggered their "run response." The issue is not whether one wants to run, but rather…

  15. Emergency preparedness and response

    International Nuclear Information System (INIS)

    Griffiths, M.

    1996-01-01

    After the Chernobyl accident, it became painfully obvious to the international community that there was an urgent need to establish a system for the coordination of international disaster assistance. It became the task of the United Nations Office for Disaster Relief (UNDRO) to develop such a system. The former UNDRO was subsumed into the Department of Humanitarian Affairs (DHA), established in January 1992 on the basis of UN General Assembly Resolution 46/182 adopted in December 1991, and the disaster relief system presently found in DHA is a further evolution of the system established by UNDRO. One particular importance in relation to nuclear accidents is the fact that UNDRO and the International Atomic Energy Agency (IAEA) signed a Memorandum of Understanding defining their respective responsibilities and the need for cooperation in case of accidents involving the unintentional release of nuclear radiation. In essence, the MOU makes it clear that the responsibilities of the IAEA, in connection with accidents at Nuclear Power Plants, related to the technical and radiological aspects, in particular to accident prevention, to the on-site preparedness, and to remedial measures within the 30-km zone outside the NPP. DHA's responsibilities, on the other hand, relate to the general preparedness and the rescue efforts outside the 30 km zone. In this respect, the preparedness and emergency response system is no different from the system employed in any other type of sudden-onset emergency

  16. Socially responsible firms

    NARCIS (Netherlands)

    Ferrell, A.; Liang, Hao; Renneboog, Luc

    2016-01-01

    In the corporate finance tradition, starting with Berle and Means (1932), corporations should generally be run to maximize shareholder value. The agency view of corporate social responsibility (CSR) considers CSR an agency problem and a waste of corporate resources. Given our identification strategy

  17. Decoupling Responsible Management Education

    DEFF Research Database (Denmark)

    Rasche, Andreas; Gilbert, Dirk Ulrich

    2015-01-01

    This article examines under what conditions business schools may decouple the structural effects of their engagement in responsible management education from actual organizational practices. We argue that schools may be unable to match rising institutional pressures to publicly commit to responsi......This article examines under what conditions business schools may decouple the structural effects of their engagement in responsible management education from actual organizational practices. We argue that schools may be unable to match rising institutional pressures to publicly commit...... to responsible management education with their limited internal capacity for change. Our analysis proposes that decoupling is likely if schools (a) are exposed to resource stringency, (b) face overt or covert resistance against change processes, (c) are confronted with competing institutional pressures, and (d......) perceive institutional demands as ambiguous. We discuss two implications of this proposition. On one hand, decoupling can cause dissonant legitimacy perceptions, leading to cynicism around responsible management education within business schools. On the other hand, a temporary inconsistency between talk...

  18. [Responsibility, compassion and ethics].

    Science.gov (United States)

    Furstenberg, Cécile

    2016-01-01

    The concepts of responsibility and compassion are fundamental in ethics. These notions help to safeguard humaneness, especially in the field of health care and notably in palliative care. These concepts can be put into practice by caregivers and applied to daily practice. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  19. Rethinking Moral Responsibility

    NARCIS (Netherlands)

    Vedder, A.H.; Johnson, D.; Moor, J.; Tavani, H.

    2000-01-01

    Questions regarding the moral responsibility of Internet access and service providers relating to possible negative aspects of information on the Internet call for a reassessment of the ways in which we think about attributing blame, guilt, and duties of reparation and compensation. They invite us

  20. Implementing Responsibility Centre Budgeting

    Science.gov (United States)

    Vonasek, Joseph

    2011-01-01

    Recently, institutes of higher education (universities) have shown a renewed interest in organisational structures and operating methodologies that generate productivity and innovation; responsibility centre budgeting (RCB) is one such process. This paper describes the underlying principles constituting RCB, its origin and structural elements, and…

  1. Radio-adaptive response

    International Nuclear Information System (INIS)

    Ikushima, T.

    1992-01-01

    An adaptive response to radiation stress was found as a suppressed induction of chromosomal damage including micronuclei and sister chromatid exchanges in cultured Chinese hamster V79 cells pre-exposed to very low doses of ionizing radiations. The mechanism underlying this novel chromosomal response, called 'radio-adaptive response (RAR)' has been studied progressively. The following results were obtained in recent experiments. 1. Low doses of β-rays from tritiated water (HTO) as well as tritium-thymidine can cause RAR. 2. Thermal neutrons, a high LET radiation, can not act as tritium β-rays or γ-rays. 3. The RAR expression is suppressed not only by the treatment with an inhibitor of protein synthesis but also by RNA synthesis inhibition. 4. Several proteins are newly synthesized concurrently with the RAR expression after the adapting doses, viewed by two-dimensional electrophoresis of cellular proteins. These results suggests that the RAR might be a cellular stress response to a signal produced preferentially by very low doses of low LET radiation under restricted conditions, accompany the inducible specific gene expression. (author)

  2. Socially Responsible Firms

    NARCIS (Netherlands)

    Renneboog, L.D.R.; Liang, H.; Ferrell, A.

    2014-01-01

    In the corporate finance tradition starting with Berle & Means (1923), corporations should generally be run so as to maximize shareholder value. The agency view of corporate social responsibility (CSR) generally considers CSR as a managerial agency problem and a waste of corporate resources, since

  3. Multimodal responsive action

    DEFF Research Database (Denmark)

    Oshima, Sae

    in haircutting sessions involve people’s subjective perspectives, adding another layer of delicacy. In this context, the participants not only orient to the general preference for agreement/alignment, but also to the client’s autonomous evaluation (as opposed to response produced out of mere social courtesy...

  4. Luxury organizations and responsibility

    DEFF Research Database (Denmark)

    Montesa, Farah; Rohrbeck, René

    2014-01-01

    In this article, findings from previous research, almost forty examples of responsible practices in luxury firms, were clustered and eight generic tools were revealed to advance sustainability. These tools are posed as questions to assess the luxury firm’s level of sustainability and to plan...

  5. Definitions of social responsibility

    NARCIS (Netherlands)

    Planken, B.C.

    2013-01-01

    The role of Corporate Social Responsibility in the business world has developed from a fig leaf marketing front into an important aspect of corporate behavior over the past several years. Sustainable strategies are valued, desired and deployed more and more by relevant players in many industries all

  6. Institutional Autonomy and Responsibility.

    Science.gov (United States)

    Hargadon, Fred

    1981-01-01

    The diversity in college admissions policies is described and the relationship between these policies and admissions testing is explained. The consequences of government regulation of testing is discussed. Colleges are urged to defend their autonomy in admissions and to act responsibly in that respect. (Author/AL)

  7. GABA expression and regulation by sensory experience in the developing visual system.

    Directory of Open Access Journals (Sweden)

    Loïs S Miraucourt

    Full Text Available The developing retinotectal system of the Xenopus laevis tadpole is a model of choice for studying visual experience-dependent circuit maturation in the intact animal. The neurotransmitter gamma-aminobutyric acid (GABA has been shown to play a critical role in the formation of sensory circuits in this preparation, however a comprehensive neuroanatomical study of GABAergic cell distribution in the developing tadpole has not been conducted. We report a detailed description of the spatial expression of GABA immunoreactivity in the Xenopus laevis tadpole brain at two key developmental stages: stage 40/42 around the onset of retinotectal innervation and stage 47 when the retinotectal circuit supports visually-guided behavior. During this period, GABAergic neurons within specific brain structures appeared to redistribute from clusters of neuronal somata to a sparser, more uniform distribution. Furthermore, we found that GABA levels were regulated by recent sensory experience. Both ELISA measurements of GABA concentration and quantitative analysis of GABA immunoreactivity in tissue sections from the optic tectum show that GABA increased in response to a 4 hr period of enhanced visual stimulation in stage 47 tadpoles. These observations reveal a remarkable degree of adaptability of GABAergic neurons in the developing brain, consistent with their key contributions to circuit development and function.

  8. The role of GABA in the hypoxia tolerance of the epaulette shark

    International Nuclear Information System (INIS)

    Wise, G.; Mulvey, J.; Renshaw, G.M.C.; Dodd, P.R.

    1998-01-01

    Full text: The epaulette shark responds to hypoxia with brain hypometabolism which is correlated with increased levels of gamma-aminobutyric acid (GABA). We examined GABA-like immunoreactivity (GABA-IR) and the density and binding characteristics of GABA A receptors in the Epaulette shark brainstem. These studies were conducted to investigate changes in response to hypoxia. Experimental animals were exposed to eight cycles of an extreme hypoxic regimen (5% of normoxia). Animals were anaesthetised with 80mg/L of MS222 and the brain was dissected and processed either for immunohistochemistry or receptor ligand binding. Membranes were prepared at 4 deg C according to a previously reported protocol and the binding characteristics of [ 3 H]flunitrazeparn ([ 3 H]FNZ) were examined using an in vitro centrifugation assay. We report on the effect of hypoxia on specific [ 3 H]FNZ binding characteristics. GABA-IR was detected using a primary antibody dilution of 1:15 000 and the Vector ABC method. We report that an overall increase in the optical density of GABA-IR occurs with significant increases in three out of the four brainstem nuclei examined in experimental animals. The results of these studies are discussed in conjunction with the hypoxia-tolerance .of the epaulette shark. Copyright (1998) Australian Neuroscience Society

  9. GABA and Gap Junctions in the Development of Synchronized Activity in Human Pluripotent Stem Cell-Derived Neural Networks

    Science.gov (United States)

    Mäkinen, Meeri Eeva-Liisa; Ylä-Outinen, Laura; Narkilahti, Susanna

    2018-01-01

    The electrical activity of the brain arises from single neurons communicating with each other. However, how single neurons interact during early development to give rise to neural network activity remains poorly understood. We studied the emergence of synchronous neural activity in human pluripotent stem cell (hPSC)-derived neural networks simultaneously on a single-neuron level and network level. The contribution of gamma-aminobutyric acid (GABA) and gap junctions to the development of synchronous activity in hPSC-derived neural networks was studied with GABA agonist and antagonist and by blocking gap junctional communication, respectively. We characterized the dynamics of the network-wide synchrony in hPSC-derived neural networks with high spatial resolution (calcium imaging) and temporal resolution microelectrode array (MEA). We found that the emergence of synchrony correlates with a decrease in very strong GABA excitation. However, the synchronous network was found to consist of a heterogeneous mixture of synchronously active cells with variable responses to GABA, GABA agonists and gap junction blockers. Furthermore, we show how single-cell distributions give rise to the network effect of GABA, GABA agonists and gap junction blockers. Finally, based on our observations, we suggest that the earliest form of synchronous neuronal activity depends on gap junctions and a decrease in GABA induced depolarization but not on GABAA mediated signaling. PMID:29559893

  10. Genetic and radiation hybrid mapping of the hyperekplexia region on chromosome 5q

    Energy Technology Data Exchange (ETDEWEB)

    Ryan, S.G.; O' Connell, P. (Univ. of Texas Health Science Center, San Antonio (United States)); Dixon, M.J. (Univ. of Manchester (United Kingdom)); Nigro, M.A. (Wayne State Univ., Detroit, MI (United States)); Kelts, K.A. (Black Hills Neurology, Rapid City, SD (United States)); Markand, O.N. (Indiana Univ., Indianopolis (United States)); Shiang, R.; Wasmuth, J.J. (Univ. of California, Irvine (United States)); Terry, J.C.

    1992-12-01

    Hyperekplexia, or startle disease (STHE), is an autosomal dominant neurologic disorder characterized by muscular rigidity of central nervous system origin, particularly in the neonatal period, and by an exaggerated startle response to sudden, unexpected acoustic or tactile stimuli. STHE responds dramatically to the benzodiazepine drug clonazepam, which acts at gamma-aminobutyric acid type A (GABA-A) receptors. The STHE locus (STHE) was recently assigned to chromosome 5q, on the basis of tight linkage to the colony-stimulating factor 1-receptor (CSF1-R) locus in a single large family. The authors performed linkage analysis in the original and three additional STHE pedigrees with eight chromosome 5q microsatellite markers and placed several of the most closely linked markers on an existing radiation hybrid (RH) map of the region. The results provide strong evidence for genetic locus homogeneity and assign STHE to a 5.9-cM interval defined by CSF1-R and D5S379, which are separated by an RH map distance of 74 centirays (roughly 2.2-3.7 Mb). Two polymorphic markers (D5S119 and D5S209) lie within this region, but they could not be ordered with respect to STHE. RH mapping eliminated the candidate genes GABRA1 and GABRG2, which encode GABA-A receptor components, by showing that they are telomeric to the target region. 45 refs., 4 figs., 4 tabs.

  11. GABA and Gap Junctions in the Development of Synchronized Activity in Human Pluripotent Stem Cell-Derived Neural Networks.

    Science.gov (United States)

    Mäkinen, Meeri Eeva-Liisa; Ylä-Outinen, Laura; Narkilahti, Susanna

    2018-01-01

    The electrical activity of the brain arises from single neurons communicating with each other. However, how single neurons interact during early development to give rise to neural network activity remains poorly understood. We studied the emergence of synchronous neural activity in human pluripotent stem cell (hPSC)-derived neural networks simultaneously on a single-neuron level and network level. The contribution of gamma-aminobutyric acid (GABA) and gap junctions to the development of synchronous activity in hPSC-derived neural networks was studied with GABA agonist and antagonist and by blocking gap junctional communication, respectively. We characterized the dynamics of the network-wide synchrony in hPSC-derived neural networks with high spatial resolution (calcium imaging) and temporal resolution microelectrode array (MEA). We found that the emergence of synchrony correlates with a decrease in very strong GABA excitation. However, the synchronous network was found to consist of a heterogeneous mixture of synchronously active cells with variable responses to GABA, GABA agonists and gap junction blockers. Furthermore, we show how single-cell distributions give rise to the network effect of GABA, GABA agonists and gap junction blockers. Finally, based on our observations, we suggest that the earliest form of synchronous neuronal activity depends on gap junctions and a decrease in GABA induced depolarization but not on GABA A mediated signaling.

  12. Initial study on the possible mechanisms involved in the effects of high doses of perfluorooctane sulfonate (PFOS) on prolactin secretion.

    Science.gov (United States)

    Salgado, R; Pereiro, N; López-Doval, S; Lafuente, A

    2015-09-01

    Perfluorooctane sulfonate (PFOS) is a fluorinated organic compound. This chemical is neurotoxic and can alter the pituitary secretion. This is an initial study aimed at knowing the toxic effects of high doses of PFOS on prolactin secretion and the possible mechanisms involved in these alterations. For that, adult male rats were orally treated with 3.0 and 6.0 mg of PFOS/kg body weight (b.w.)/day for 28 days. At the end of the treatment, the serum levels of prolactin and estradiol as well as the concentration of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and gamma-aminobutyric acid (GABA) were quantified in the anterior and in the mediobasal hypothalamus. PFOS, at the administered doses, reduced prolactin and estradiol secretion, increased the concentration of dopamine and GABA in the anterior hypothalamus, and decreased the ratios DOPAC/dopamine and HVA/dopamine in this same hypothalamic area. The outcomes reported in this study suggest that (1) high doses of PFOS inhibit prolactin secretion in adult male rats; (2) only the periventricular-hypophysial dopaminergic (PHDA) neurons seem to be involved in this inhibitory effect but not the tuberoinfundibular dopaminergic (TIDA) and the tuberohypophysial dopaminergic (THDA) systems; (3) GABAergic cells from the paraventricular and supraoptic nuclei could be partially responsible for the PFOS action on prolactin secretion; and finally (4) estradiol might take part in the inhibition exerted by elevated concentration of PFOS on prolactin release. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. In vivo temporal property of GABAergic neural transmission in collateral feed-forward inhibition system of hippocampal-prefrontal pathway.

    Science.gov (United States)

    Takita, Masatoshi; Kuramochi, Masahito; Izaki, Yoshinori; Ohtomi, Michiko

    2007-05-30

    Anatomical evidence suggests that rat CA1 hippocampal afferents collaterally innervate excitatory projecting pyramidal neurons and inhibitory interneurons, creating a disynaptic, feed-forward inhibition microcircuit in the medial prefrontal cortex (mPFC). We investigated the temporal relationship between the frequency of paired synaptic transmission and gamma-aminobutyric acid (GABA)ergic receptor-mediated modulation of the microcircuit in vivo under urethane anesthesia. Local perfusions of a GABAa antagonist (-)-bicuculline into the mPFC via microdialysis resulted in a statistically significant disinhibitory effect on intrinsic GABA action, increasing the first and second mPFC responses following hippocampal paired stimulation at interstimulus intervals of 100-200 ms, but not those at 25-50 ms. This (-)-bicuculline-induced disinhibition was compensated by the GABAa agonist muscimol, which itself did not attenuate the intrinsic oscillation of the local field potentials. The perfusion of a sub-minimal concentration of GABAb agonist (R)-baclofen slightly enhanced the synaptic transmission, regardless of the interstimulus interval. In addition to the tonic control by spontaneous fast-spiking GABAergic neurons, it is clear the sequential transmission of the hippocampal-mPFC pathway can phasically drive the collateral feed-forward inhibition system through activation of a GABAa receptor, bringing an active signal filter to the various types of impulse trains that enter the mPFC from the hippocampus in vivo.

  14. The neurophysiology of the sexual cycle.

    Science.gov (United States)

    Argiolas, A; Melis, M R

    2003-01-01

    The cycle of sexual activity in men and women occurs in 4 phases--excitation, plateau, orgasm, resolution--which are guided by sexual desire. Male sexual activity is characterized by erection, seminal emission and ejaculation (orgasm), whereas female sexual activity is characterized by vaginal lubrication, erection of the clitoris and orgasm. These responses are under the control of numerous central and peripheral neural systems. The central supraspinal systems are mainly localized in the limbic system (olfactory nuclei, medial preoptic area, nucleus accumbens, amygdala, hippocampus etc.), in the hypothalamus and its nuclei (paraventricular and ventromedial nuclei). Neural information travels through the brain stem, the medulla oblongata, the spinal cord and the autonomous nervous system to the genital apparatus. While we have very detailed knowledge of the neural mechanism, which controls the function of the male and female genital organs, in particular those mediating erection, very little is known of the central mechanism involved. Nevertheless, several neurotransmitters and neuropeptides, such as dopamine, glutamic acid, nitric oxide, oxytocin, ACTH-MSH peptides, are known to facilitate sexual function, while serotonin, gamma-aminobutyric acid (GABA) and opioid peptides reduce it. At the level of the paraventricular nucleus a group of oxytocinergic neurons projecting to extra-hypothalamic brain areas, including the spinal cord, have been identified, which facilitate erectile function and copulation when activated and reduce both when inhibited. Although the majority of results, which have clarified the mechanisms involved, have been performed in males, it is believed that similar mechanisms are also operative in females.

  15. Levodopa-induced Dyskinesia: Clinical Features, Pathophysiology, and Medical Management.

    Science.gov (United States)

    Pandey, Sanjay; Srivanitchapoom, Prachaya

    2017-01-01

    Levodopa-induced dyskinesia (LID) is commonly seen in Parkinson's disease patients treated with levodopa. This side effect is usually encountered after long duration of treatment, but occasionally, this may be seen even after few days or months of treatment. LID is broadly classified as peak-dose dyskinesia, wearing-off or off-period dyskinesia, and diphasic dyskinesia. Pathogenesis of LID is complex, and different neurotransmitters such as dopamine, glutamine, adenosine, and gamma-aminobutyric acid play important role altering the normal physiology of direct and indirect pathway of cortico-basal ganglia-thalamic loop responsible for fine motor control. Treatment of LID requires careful history taking and clinical examination to find the type of dyskinesia as different approach is required for different types. Changes in dopaminergic medication including continuous dopaminergic stimulation are very helpful in the management of peak-dose dyskinesia. Different types of surgical approaches including unilateral pallidotomy and deep brain stimulation have given very good result in patients, who cannot be managed by medications alone. The surgical management of LID is dealt with in detail in another review in this series.

  16. [Learning disorders in neurofibromatosis type 1].

    Science.gov (United States)

    Garcia-Penas, J J

    2017-02-24

    Neurocognitive deficits and academic learning difficulties are the most common neurologic complication of neurofibromatosis type 1 (NF1) in childhood and can be responsible for significant lifetime morbidity. Children with NF1 show impairments in attention, visual perception, language, executive function, academic skills, and behavior. Studies in animal models suggest that the learning disabilities associated with NF1 are caused by excessive Ras activity that leads to increased gamma-aminobutyric acid (GABA) inhibition and to decreased long-term potentiation. To describe the frequency, severity, typology, and natural course of specific cognitive deficits in children with NF1. Cognitive and behavioral disorders affect between 50-80% of all children with NF1. We can define three subtypes of cognitive profiles in children with NF1 and learning disorder, including global learning disorder, specific learning disorder, and isolated attention deficit hyperactivity disorder. The most common cognitive deficits are connected with visual-spatial impairment, however working memory and executive function deficits associated with prefrontal cortex dysfunction are also important. There is an extremely high frequency of cognitive problems in children with NF1, making cognitive dysfunction the most common complication to affect quality of life in these children. Early diagnosis and treatment of learning disorders in these patients leads to improved academic outcome.

  17. Stress metabolism in green coffee beans (Coffea arabica L.): expression of dehydrins and accumulation of GABA during drying.

    Science.gov (United States)

    Kramer, Daniela; Breitenstein, Björn; Kleinwächter, Maik; Selmar, Dirk

    2010-04-01

    In order to produce tradeable standard green coffee, processed beans must be dried. The drying procedure affects the abundance of relevant aroma substances, e.g. carbohydrates. Using molecular tools, the corresponding metabolic basis is analyzed. A decrease in water potential of the still living coffee seeds induces massive drought stress responses. As a marker for these stress reactions, accumulation of a general stress metabolite, GABA (gamma-aminobutyric acid), and associated gene expression of drought stress-associated dehydrins were monitored. The results of this study indicate that metabolism in drying coffee beans is quite complex since several events trigger accumulation of GABA. The first peak of GABA accumulation during drying is correlated with expression of isocitrate lyase and thus with ongoing germination processes in coffee seeds. Two subsequent peaks of GABA accumulation correspond to maxima of dehydrin gene expression and are thought to be induced directly by drought stress in the embryo and endosperm tissue, respectively. Apart from the significance for understanding basic seed physiology, metabolic changes in coffee seeds during processing provide valuable information for understanding the role and effect of the steps of green coffee processing on the quality of the resulting coffee.

  18. First evidence that drugs of abuse produce behavioral sensitization and cross sensitization in planarians.

    Science.gov (United States)

    Rawls, Scott M; Patil, Tavni; Yuvasheva, Ekaternia; Raffa, Robert B

    2010-07-01

    Behavioral sensitization in mammals, including humans, is sensitive to factors such as administration route, testing environment, and pharmacokinetic confounds, unrelated to the drugs themselves that are difficult to eliminate. Simpler animals less susceptible to these confounding influences may be advantageous substitutes for studying sensitization. We tested this hypothesis by determining whether planarians display sensitization and cross sensitization to cocaine and glutamate. Planarian hyperactivity was quantified as the number of C-like hyperkinesias during a 1-min drug exposure. Planarians exposed initially to cocaine (or glutamate) on day 1 were challenged with cocaine (or glutamate) after 2 or 6 days of abstinence. Acute cocaine or glutamate produced concentration-related hyperactivity. Cocaine or glutamate challenge after 2 and 6 days of abstinence enhanced the hyperactivity, indicating the substances produced planarian behavioral sensitization. Cross-sensitization experiments showed that cocaine produced greater hyperactivity in planarians earlier exposed to glutamate than in glutamate-naive planarians, and vice versa. Behavioral responses were pharmacologically selective because neither scopolamine nor caffeine produced planarian behavioral sensitization despite causing hyperactivity after initial administration, and acute gamma-aminobutyric acid did not cause hyperactivity. Demonstration of pharmacologically selective behavioral sensitization in planarians suggests that these flatworms represent a sensitive in-vivo model to study cocaine behavioral sensitization and to screen potential abuse-deterrent therapeutics.

  19. Feeling safe in the plane: neural mechanisms underlying superior action control in airplane pilot trainees--a combined EEG/MRS study.

    Science.gov (United States)

    Yildiz, Ali; Quetscher, Clara; Dharmadhikari, Shalmali; Chmielewski, Witold; Glaubitz, Benjamin; Schmidt-Wilcke, Tobias; Edden, Richard; Dydak, Ulrike; Beste, Christian

    2014-10-01

    In day-to-day life, we need to apply strategies to cascade different actions for efficient unfolding of behavior. While deficits in action cascading are examined extensively, almost nothing is known about the neuronal mechanisms mediating superior performance above the normal level. To examine this question, we investigate action control in airplane pilot trainees. We use a stop-change paradigm that is able to estimate the efficiency of action cascading on the basis of mathematical constraints. Behavioral and EEG data is analyzed along these constraints and integrated with neurochemical data obtained using Magnetic Resonance Spectroscopy (MRS) from the striatal gamma-aminobutyric acid (GABA) -ergic system. We show that high performance in action cascading, as exemplified in airplane pilot trainees, can be driven by intensified attentional processes, circumventing response selection processes. The results indicate that the efficiency of action cascading and hence the speed of responding as well as attentional gating functions are modulated by striatal GABA and Glutamate + Glutamine concentrations. In superior performance in action cascading similar increases in the concentrations of GABA and Glutamate + Glutamine lead to stronger neurophysiological and behavioral effects as compared to subjects with normal performance in action cascading. Copyright © 2014 Wiley Periodicals, Inc.

  20. Clinical Use of CSF Neurotransmitters.

    Science.gov (United States)

    Rodan, Lance H; Gibson, K Michael; Pearl, Phillip L

    2015-10-01

    Cerebrospinal fluid neurotransmitter collection, analysis, and follow-up are integral to the diagnosis and management of multiple inborn metabolic errors, some of which require prompt identification and intervention to improve outcome. Cerebrospinal fluid pterins and monoamine metabolites are diagnostic in a range of primary neurotransmitter disorders, including disorders of biogenic amine synthesis, metabolism, and transport. Recently described mutations of the human dopamine transporter are associated with an elevated cerebrospinal fluid homovanillic acid:hydroxyindoleacetic acid ratio. Disorders of pyridoxine metabolism are also detectable via cerebrospinal fluid quantification of bioamines, amino acids, and pyridoxal-5-phosphate levels. Cerebrospinal fluid amino acids are diagnostic in disorders of gamma aminobutyric acid, glycine, and serine metabolism. A wide range of acquired and genetic disorders has also been associated with secondary alterations in cerebrospinal fluid levels of monoamine metabolites, glycine, and neopterin. Lumbar puncture is required to detect abnormal cerebrospinal fluid metabolites in a significant proportion of these disorders, including treatable entities such as dopa-responsive deficiencies of guanosine-5'-triphosphate cyclohydrolase I (Segawa disease), sepiapterin reductase, and tyrosine hydroxylase. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Ménage à trois: the role of neurotransmitters in the energy metabolism of astrocytes, glutamatergic, and GABAergic neurons.

    Science.gov (United States)

    Calvetti, Daniela; Somersalo, Erkki

    2012-08-01

    This work is a computational study based on a new detailed metabolic network model comprising well-mixed compartments representing separate cytosol and mitochondria of astrocytes, glutamatergic and gamma aminobutyric acid (GABA)ergic neurons, communicating through an extracellular space compartment and fed by arterial blood flow. Our steady-state analysis assumes statistical mass balance of both carbons and amino groups. The study is based on Bayesian flux balance analysis, which uses Markov chain Monte Carlo sampling techniques and provides a quantitative description of steady states when the two exchangers aspartate-glutamate carrier (AGC1) and oxoglutarate carrier (OGC) in the malate-aspartate shuttle in astrocyte are not in equilibrium, as recent studies suggest. It also highlights the importance of anaplerotic reactions, pyruvate carboxylase in astrocyte and malic enzyme in neurons, for neurotransmitter synthesis and recycling. The model is unbiased with respect to the glucose partitioning between cell types, and shows that determining the partitioning cannot be done by stoichiometric constraints alone. Furthermore, the intercellular lactate trafficking is found to depend directly on glucose partitioning, suggesting that a steady state may support different scenarios. At inhibitory steady state, characterized by high rate of GABA release, there is elevated oxidative activity in astrocyte, not in response to specific energetic needs.

  2. GABA and Gap Junctions in the Development of Synchronized Activity in Human Pluripotent Stem Cell-Derived Neural Networks

    Directory of Open Access Journals (Sweden)

    Meeri Eeva-Liisa Mäkinen

    2018-03-01

    Full Text Available The electrical activity of the brain arises from single neurons communicating with each other. However, how single neurons interact during early development to give rise to neural network activity remains poorly understood. We studied the emergence of synchronous neural activity in human pluripotent stem cell (hPSC-derived neural networks simultaneously on a single-neuron level and network level. The contribution of gamma-aminobutyric acid (GABA and gap junctions to the development of synchronous activity in hPSC-derived neural networks was studied with GABA agonist and antagonist and by blocking gap junctional communication, respectively. We characterized the dynamics of the network-wide synchrony in hPSC-derived neural networks with high spatial resolution (calcium imaging and temporal resolution microelectrode array (MEA. We found that the emergence of synchrony correlates with a decrease in very strong GABA excitation. However, the synchronous network was found to consist of a heterogeneous mixture of synchronously active cells with variable responses to GABA, GABA agonists and gap junction blockers. Furthermore, we show how single-cell distributions give rise to the network effect of GABA, GABA agonists and gap junction blockers. Finally, based on our observations, we suggest that the earliest form of synchronous neuronal activity depends on gap junctions and a decrease in GABA induced depolarization but not on GABAA mediated signaling.

  3. Activity-Dependent Bidirectional Regulation of GAD Expression in a Homeostatic Fashion Is Mediated by BDNF-Dependent and Independent Pathways

    Science.gov (United States)

    Hanno-Iijima, Yoko; Tanaka, Masami; Iijima, Takatoshi

    2015-01-01

    Homeostatic synaptic plasticity, or synaptic scaling, is a mechanism that tunes neuronal transmission to compensate for prolonged, excessive changes in neuronal activity. Both excitatory and inhibitory neurons undergo homeostatic changes based on synaptic transmission strength, which could effectively contribute to a fine-tuning of circuit activity. However, gene regulation that underlies homeostatic synaptic plasticity in GABAergic (GABA, gamma aminobutyric) neurons is still poorly understood. The present study demonstrated activity-dependent dynamic scaling in which NMDA-R (N-methyl-D-aspartic acid receptor) activity regulated the expression of GABA synthetic enzymes: glutamic acid decarboxylase 65 and 67 (GAD65 and GAD67). Results revealed that activity-regulated BDNF (brain-derived neurotrophic factor) release is necessary, but not sufficient, for activity-dependent up-scaling of these GAD isoforms. Bidirectional forms of activity-dependent GAD expression require both BDNF-dependent and BDNF-independent pathways, both triggered by NMDA-R activity. Additional results indicated that these two GAD genes differ in their responsiveness to chronic changes in neuronal activity, which could be partially caused by differential dependence on BDNF. In parallel to activity-dependent bidirectional scaling in GAD expression, the present study further observed that a chronic change in neuronal activity leads to an alteration in neurotransmitter release from GABAergic neurons in a homeostatic, bidirectional fashion. Therefore, the differential expression of GAD65 and 67 during prolonged changes in neuronal activity may be implicated in some aspects of bidirectional homeostatic plasticity within mature GABAergic presynapses. PMID:26241953

  4. Nerve growth factor actions on the brain

    International Nuclear Information System (INIS)

    Martinez, H.J.

    1989-01-01

    We examined the effect of the trophic protein, nerve growth factor (NGF), on cultures of fetal rat neostriatum and basal forebrain-medial septal area (BF-MS) to define its role in brain development. Treatment of cultures with NGF resulted in an increase in the specific activity of the cholinergic enzyme choline acetyltransferase (CAT) in both brain areas. CAT was immunocytochemically localized to neurons. In the BF-MS, NGF treatment elicited a marked increase in staining intensity and an apparent increase in the number of CAT-positive neurons. Moreover, treatment of BF-MS cultures with NGF increased the activity of acetylcholinesterase, suggesting that the cholinergic neuron as a whole was affected. To begin defining mechanisms of action of NGF in the BF-MS, we detected NGF receptors by two independent methods. Receptors were localized to two different cellular populations: neuron-like cells, and non-neuron-like cells. Dissociation studies with [ 125 I]NGF suggested that high affinity receptors were localized to the neuron-like population. Only low-affinity receptors were localized to the non-neuron-like cells. Moreover, employing combined immunocytochemistry and [ 125 I]NGF autoradiography, we detected a subpopulation of CAT-containing neutrons that exhibited high-affinity binding. Unexpectedly, a gamma-aminobutyric acid (GABA)-containing cell group also expressed high affinity binding. However, only subsets of cholinergic or GABA neurons expressed high-affinity biding, suggesting that these transmitter populations are composed of differentially response subpopulations

  5. Involvement of GABAergic pathway in the sedative activity of apigenin, the main flavonoid from Passiflora quadrangularis pericarp

    Directory of Open Access Journals (Sweden)

    Andressa C. Gazola

    Full Text Available Abstract In the current study we showed that oral administration of an aqueous extract of Passiflora quadrangularis L., Passifloraceae, pericarp results in a significant prolongation of the sleep duration in mice evaluated in the ethyl ether-induced hypnosis test which indicates sedative effects. Apigenin, the main flavonoid of the extract, induced a similar sedative response when applied alone, at a dose equivalent to that found in the extract, suggesting that apigenin is mediating the sedative effects of P. quadrangularis extract. In addition, the sedative effect of apigenin was blocked by pretreatment with the benzodiazepine antagonist flumazenil (1 mg/kg, suggesting an interaction of apigenin with gamma-aminobutyric acid type A (GABAA receptors. However, apigenin at concentrations 0.1–50 µM failed to enhance GABA-induced currents through GABAA receptors (α1β2γ2S expressed in Xenopus oocytes. Nevertheless, based on our results, we suggest that the in vivo sedative effect of the P. quadrangularis extract and its main flavonoid apigenin maybe be due to an enhancement of the GABAergic system.

  6. Actions of insecticides on the insect GABA receptor complex

    Energy Technology Data Exchange (ETDEWEB)

    Bermudez, I.; Hawkins, C.A.; Taylor, A.M.; Beadle, D.J. (School of Biological and Molecular Sciences, Oxford Polytechnic, Headington, Oxford (England))

    1991-01-01

    The actions of insecticides on the insect gamma-aminobutyric acid (GABA) receptor were investigated using (35S)t-butylbicyclophosphorothionate (( 35S)TBPS) binding and voltage-clamp techniques. Specific binding of (35S)TBPS to a membrane homogenate derived from the brain of Locusta migratoria locusts is characterised by a Kd value of 79.3 {plus minus} 2.9 nM and a Bmax value of 1770 {plus minus} 40 fmol/mg protein. (35S)TBPS binding is inhibited by mM concentrations of barbiturates and benzodiazepines. In contrast dieldrin, ivermectin, lindane, picrotoxin and TBPS are inhibitors of (35S)TBPS binding at the nanomolar range. Bicuculline, baclofen and pyrethroid insecticides have no effect on (35S)TBPS binding. These results are similar to those obtained in electrophysiological studies of the current elicited by GABA in both Locusta and Periplaneta americana central neurones. Noise analysis of the effects of lindane, TBPS, dieldrin and picrotoxin on the cockroach GABA responses reveals that these compounds decrease the variance of the GABA-induced current but have no effect on its mean open time. All these compounds, with the exception of dieldrin, significantly decrease the conductance of GABA-evoked single current.

  7. Genetic dissection of behavioural and autonomic effects of Delta(9-tetrahydrocannabinol in mice.

    Directory of Open Access Journals (Sweden)

    Krisztina Monory

    2007-10-01

    Full Text Available Marijuana and its main psychotropic ingredient Delta(9-tetrahydrocannabinol (THC exert a plethora of psychoactive effects through the activation of the neuronal cannabinoid receptor type 1 (CB1, which is expressed by different neuronal subpopulations in the central nervous system. The exact neuroanatomical substrates underlying each effect of THC are, however, not known. We tested locomotor, hypothermic, analgesic, and cataleptic effects of THC in conditional knockout mouse lines, which lack the expression of CB1 in different neuronal subpopulations, including principal brain neurons, GABAergic neurons (those that release gamma aminobutyric acid, cortical glutamatergic neurons, and neurons expressing the dopamine receptor D1, respectively. Surprisingly, mice lacking CB1 in GABAergic neurons responded to THC similarly as wild-type littermates did, whereas deletion of the receptor in all principal neurons abolished or strongly reduced the behavioural and autonomic responses to the drug. Moreover, locomotor and hypothermic effects of THC depend on cortical glutamatergic neurons, whereas the deletion of CB1 from the majority of striatal neurons and a subpopulation of cortical glutamatergic neurons blocked the cataleptic effect of the drug. These data show that several important pharmacological actions of THC do not depend on functional expression of CB1 on GABAergic interneurons, but on other neuronal populations, and pave the way to a refined interpretation of the pharmacological effects of cannabinoids on neuronal functions.

  8. Activation of synaptic and extrasynaptic glycine receptors by taurine in preoptic hypothalamic neurons.

    Science.gov (United States)

    Bhattarai, Janardhan Prasad; Park, Soo Joung; Chun, Sang Woo; Cho, Dong Hyu; Han, Seong Kyu

    2015-11-03

    Taurine is an essential amino-sulfonic acid having a fundamental function in the brain, participating in both cell volume regulation and neurotransmission. Using a whole cell voltage patch clamp technique, the taurine-activated neurotransmitter receptors in the preoptic hypothalamic area (PHA) neurons were investigated. In the first set of experiments, different concentrations of taurine were applied on PHA neurons. Taurine-induced responses were concentration-dependent. Taurine-induced currents were action potential-independent and sensitive to strychnine, suggesting the involvement of glycine receptors. In addition, taurine activated not only α-homomeric, but also αβ-heteromeric glycine receptors in PHA neurons. Interestingly, a low concentration of taurine (0.5mM) activated glycine receptors, whereas a higher concentration (3mM) activated both glycine and gamma-aminobutyric acid A (GABAA) receptors in PHA neurons. These results suggest that PHA neurons are influenced by taurine and respond via glycine and GABAA receptors. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  9. Cardiovascular and behavioral effects produced by administration of liposome-entrapped GABA into the rat central nervous system.

    Science.gov (United States)

    Vaz, G C; Bahia, A P C O; de Figueiredo Müller-Ribeiro, F C; Xavier, C H; Patel, K P; Santos, R A S; Moreira, F A; Frézard, F; Fontes, M A P

    2015-01-29

    Liposomes are nanosystems that allow a sustained release of entrapped substances. Gamma-aminobutyric acid (GABA) is the most prevalent inhibitory neurotransmitter of the central nervous system (CNS). We developed a liposomal formulation of GABA for application in long-term CNS functional studies. Two days after liposome-entrapped GABA was injected intracerebroventricularly (ICV), Wistar rats were submitted to the following evaluations: (1) changes in mean arterial pressure (MAP), heart rate (HR) and renal sympathetic nerve activity (RSNA) to ICV injection of bicuculline methiodide (BMI) in anesthetized rats; (2) changes in cardiovascular reactivity to air jet stress in conscious rats; and (3) anxiety-like behavior in conscious rats. GABA and saline-containing pegylated liposomes were prepared with a mean diameter of 200 nm. Rats with implanted cannulas targeted to lateral cerebral ventricle (n = 5-8/group) received either GABA solution (GS), empty liposomes (EL) or GABA-containing liposomes (GL). Following (48 h) central microinjection (2 μL, 0.09 M and 99 g/L) of liposomes, animals were submitted to the different protocols. Animals that received GL demonstrated attenuated response of RSNA to BMI microinjection (GS 48 ± 9, EL 43 ± 9, GL 11 ± 8%; P central nervous system. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  10. CRYSTAL STRUCTURE OF CLOSTRIDIUM BOTULINUM NEUROTOXIN SEROTYPE B

    International Nuclear Information System (INIS)

    SWAMINATHAN, S.; ESWARAMOORTHY, S.

    2001-01-01

    The toxigenic strains of Clostridium botulinum produce seven serologically distinct types of neurotoxins labeled A - G (EC 3.4.24.69), while Clostridium tetani produces tetanus neurotoxin (EC 3.4.24.68). Botulinum and tetanus neurotoxins (BoNTs and TeNT) are produced as single inactive chains of molecular mass of approximately 150 kDa. Most of these neurotoxins are released after being cleaved into two chains, a heavy chain (HI) of 100 kDa and a light chain (L) of 50 kDa held together by an interchain disulfide bond, by tissue proteinases. BoNT/E is released as a single chain but cleaved by host proteinases[1]. Clostvidium botulinum neurotoxins are extremely poisonous proteins with their LD(sub 50) for humans in the range of 0.1 - 1 ng kg(sup -1)[2]. Botulinum neurotoxins are responsible for neuroparalytic syndromes of botulism characterized by serious neurological disorders and flaccid paralysis. BoNTs block the release of acetylcholine at the neuromuscular junction causing flaccid paralysis while TeNT blocks the release of neurotransmitters like glycine and(gamma)-aminobutyric acid (GABA) in the inhibitory interneurons of the spinal cord resulting in spastic paralysis. In spite of different clinical symptoms, their aetiological agents intoxicate neuronal cells in the same way and these toxins have similar structural organization[3

  11. Arcuate AgRP neurons and the regulation of energy balance

    Directory of Open Access Journals (Sweden)

    Céline eCansell

    2012-12-01

    Full Text Available The arcuate nucleus of the hypothalamus contains at least two crucial populations of neurons that continuously monitor signals reflecting energy status and promote the appropriate behavioral and metabolic responses to changes in energy demand. Neurons making pro-opiomelanocortin (POMC decrease food intake and increase energy expenditure through activation of G protein-coupled receptors melanocortin receptors (MCR via the release of a-melanocyte stimulating hormone. A prevailing idea until recently was that the neighboring neurons expressing the orexigenic neuropeptides, agouti-related protein (AgRP and neuropeptide Y (NPY (AgRP neurons increased feeding by opposing the anorexigenic actions of the POMC neurons. AgRP neurons activation but not POMC neurons inhibition was recently demonstrated to be necessary and sufficient to promote feeding. AgRP expressing axons were identified in mesolimbic, midbrain and pontine structure where they regulate feeding but also feeding-independent functions such as reward or peripheral nutrient partitioning. Post-synaptic Gamma aminobutyric acid (GABA, lasting in a timeline similar to neuromodulation, was identified as the core mechanism by which hunger-activated neurons regulate feeding and non-food related processes in a melanocortin independent manner.

  12. Elements of molecular machinery of GABAergic signaling in the vertebrate cholinergic neuromuscular junction.

    Science.gov (United States)

    Nurullin, Leniz F; Nikolsky, Evgeny E; Malomouzh, Artem I

    2018-04-01

    It is generally accepted that gamma-aminobutyric acid (GABA) is a signaling molecule abundant in central synapses. In a number of studies though, it has been shown that GABA signaling functions in the peripheral nervous system as well, in particular, in the synapses of sympathetic ganglia. However, there exists no firm evidence on the presence of GABAergic signaling cascade in the intercellular junctions of the somatic nerve system. By the use of immunohistochemistry methods, in the synaptic area of cholinergic neuromuscular contact in rat diaphragm, we have detected glutamate decarboxylase, the enzyme involved in synthesis of GABA, molecules of GABA, and also GAT-2, a protein responsible for transmembrane transport of GABA. Earlier we have also shown that metabotropic GABA B receptors have overlapping localization in the same compartment. Moreover, activation of GABA B receptors affects the intensity of acetylcholine release. These data taken together, allows us to suggest that in the mammalian cholinergic neuromuscular junction, GABA is synthesized and performs certain synaptic signaling function. Copyright © 2018 The Authors. Published by Elsevier GmbH.. All rights reserved.

  13. Early continuous white noise exposure alters auditory spatial sensitivity and expression of GAD65 and GABAA receptor subunits in rat auditory cortex.

    Science.gov (United States)

    Xu, Jinghong; Yu, Liping; Cai, Rui; Zhang, Jiping; Sun, Xinde

    2010-04-01

    Sensory experiences have important roles in the functional development of the mammalian auditory cortex. Here, we show how early continuous noise rearing influences spatial sensitivity in the rat primary auditory cortex (A1) and its underlying mechanisms. By rearing infant rat pups under conditions of continuous, moderate level white noise, we found that noise rearing markedly attenuated the spatial sensitivity of A1 neurons. Compared with rats reared under normal conditions, spike counts of A1 neurons were more poorly modulated by changes in stimulus location, and their preferred locations were distributed over a larger area. We further show that early continuous noise rearing induced significant decreases in glutamic acid decarboxylase 65 and gamma-aminobutyric acid (GABA)(A) receptor alpha1 subunit expression, and an increase in GABA(A) receptor alpha3 expression, which indicates a returned to the juvenile form of GABA(A) receptor, with no effect on the expression of N-methyl-D-aspartate receptors. These observations indicate that noise rearing has powerful adverse effects on the maturation of cortical GABAergic inhibition, which might be responsible for the reduced spatial sensitivity.

  14. The GABRB1 gene is associated with thalamus volume and modulates the association between thalamus volume and intelligence.

    Science.gov (United States)

    Zhu, Bi; Chen, Chuansheng; Xue, Gui; Lei, Xuemei; Li, Jin; Moyzis, Robert K; Dong, Qi; Lin, Chongde

    2014-11-15

    The GABRB1 gene encodes the beta 1 subunit of the gamma-aminobutyric acid A receptor (GABA A receptor), which is responsible for mediating inhibitory neurotransmission in the thalamus. Potential relationships between the GABRB1 gene, thalamus volume, and intelligence have been suggested by previous clinical studies, but have not been directly examined among nonclinical samples. The current study collected structural MRI, genetic, and behavioral data from 316 healthy Chinese adults (including 187 females and 129 males), and examined associations between GABRB1 variants, thalamus volume, and intelligence (measured by the Wechsler Adult Intelligence Scale Revised). After controlling for intracranial volume, sex, and age, GABRB1 genetic polymorphism at the SNP rs7435958 had the strongest association with thalamus volume (p = 0.002 and 0.00008 for left and right thalamus volumes, respectively), with GG homozygotes having smaller bilateral thalamus volumes than the other genotypes. Furthermore, there were positive correlations between bilateral thalamus volumes and intelligence, especially for GABRB1 rs7435958 GG female homozygotes (r's = 0.31 and 0.29, p intelligence with left and right thalamus volumes, respectively). This study provides the first evidence for the involvement of the GABRB1 gene in the thalamus structure and their interactive effects on intelligence. Future studies of the thalamus-intelligence associations should consider genetic factors as potential moderators. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Actions of insecticides on the insect GABA receptor complex

    International Nuclear Information System (INIS)

    Bermudez, I.; Hawkins, C.A.; Taylor, A.M.; Beadle, D.J.

    1991-01-01

    The actions of insecticides on the insect gamma-aminobutyric acid (GABA) receptor were investigated using [35S]t-butylbicyclophosphorothionate [( 35S]TBPS) binding and voltage-clamp techniques. Specific binding of [35S]TBPS to a membrane homogenate derived from the brain of Locusta migratoria locusts is characterised by a Kd value of 79.3 ± 2.9 nM and a Bmax value of 1770 ± 40 fmol/mg protein. [35S]TBPS binding is inhibited by mM concentrations of barbiturates and benzodiazepines. In contrast dieldrin, ivermectin, lindane, picrotoxin and TBPS are inhibitors of [35S]TBPS binding at the nanomolar range. Bicuculline, baclofen and pyrethroid insecticides have no effect on [35S]TBPS binding. These results are similar to those obtained in electrophysiological studies of the current elicited by GABA in both Locusta and Periplaneta americana central neurones. Noise analysis of the effects of lindane, TBPS, dieldrin and picrotoxin on the cockroach GABA responses reveals that these compounds decrease the variance of the GABA-induced current but have no effect on its mean open time. All these compounds, with the exception of dieldrin, significantly decrease the conductance of GABA-evoked single current

  16. CRYSTAL STRUCTURE OF CLOSTRIDIUM BOTULINUM NEUROTOXIN SEROTYPE B.

    Energy Technology Data Exchange (ETDEWEB)

    SWAMINATHAN,S.; ESWARAMOORTHY,S.

    2001-11-19

    The toxigenic strains of Clostridium botulinum produce seven serologically distinct types of neurotoxins labeled A - G (EC 3.4.24.69), while Clostridium tetani produces tetanus neurotoxin (EC 3.4.24.68). Botulinum and tetanus neurotoxins (BoNTs and TeNT) are produced as single inactive chains of molecular mass of approximately 150 kDa. Most of these neurotoxins are released after being cleaved into two chains, a heavy chain (HI) of 100 kDa and a light chain (L) of 50 kDa held together by an interchain disulfide bond, by tissue proteinases. BoNT/E is released as a single chain but cleaved by host proteinases [1]. Clostvidium botulinum neurotoxins are extremely poisonous proteins with their LD{sub 50} for humans in the range of 0.1 - 1 ng kg{sup -1} [2]. Botulinum neurotoxins are responsible for neuroparalytic syndromes of botulism characterized by serious neurological disorders and flaccid paralysis. BoNTs block the release of acetylcholine at the neuromuscular junction causing flaccid paralysis while TeNT blocks the release of neurotransmitters like glycine and {gamma}-aminobutyric acid (GABA) in the inhibitory interneurons of the spinal cord resulting in spastic paralysis. In spite of different clinical symptoms, their aetiological agents intoxicate neuronal cells in the same way and these toxins have similar structural organization [3].

  17. Clinical characteristics of patients with cerebellar ataxia associated with anti-GAD antibodies

    Directory of Open Access Journals (Sweden)

    Tiago Silva Aguiar

    Full Text Available ABSTRACT The enzyme glutamic acid decarboxylase (GAD, present in GABAergic neurons and in pancreatic beta cells, catalyzes the conversion of gamma-aminobutyric acid (GABA. The cerebellum is highly susceptible to immune-mediated mechanisms, with the potentially treatable autoimmune cerebellar ataxia associated with the GAD antibody (CA-GAD-ab being a rare, albeit increasingly detected condition. Few cases of CA-GAD-ab have been described. Methods This retrospective and descriptive study evaluated the clinical characteristics and outcomes of patients with CA-GAD-ab. Result Three patients with cerebellar ataxia, high GAD-ab titers and autoimmune endocrine disease were identified. Patients 1 and 2 had classic stiff person syndrome and insidious-onset cerebellar ataxia, while Patient 3 had pure cerebellar ataxia with subacute onset. Patients received intravenous immunoglobulin therapy with no response in Patients 1 and 3 and partial recovery in Patient 2. Conclusion CA-GAD-ab is rare and its clinical presentation may hamper diagnosis. Clinicians should be able to recognize this potentially treatable autoimmune cerebellar ataxia.

  18. Activity-Dependent Bidirectional Regulation of GAD Expression in a Homeostatic Fashion Is Mediated by BDNF-Dependent and Independent Pathways.

    Science.gov (United States)

    Hanno-Iijima, Yoko; Tanaka, Masami; Iijima, Takatoshi

    2015-01-01

    Homeostatic synaptic plasticity, or synaptic scaling, is a mechanism that tunes neuronal transmission to compensate for prolonged, excessive changes in neuronal activity. Both excitatory and inhibitory neurons undergo homeostatic changes based on synaptic transmission strength, which could effectively contribute to a fine-tuning of circuit activity. However, gene regulation that underlies homeostatic synaptic plasticity in GABAergic (GABA, gamma aminobutyric) neurons is still poorly understood. The present study demonstrated activity-dependent dynamic scaling in which NMDA-R (N-methyl-D-aspartic acid receptor) activity regulated the expression of GABA synthetic enzymes: glutamic acid decarboxylase 65 and 67 (GAD65 and GAD67). Results revealed that activity-regulated BDNF (brain-derived neurotrophic factor) release is necessary, but not sufficient, for activity-dependent up-scaling of these GAD isoforms. Bidirectional forms of activity-dependent GAD expression require both BDNF-dependent and BDNF-independent pathways, both triggered by NMDA-R activity. Additional results indicated that these two GAD genes differ in their responsiveness to chronic changes in neuronal activity, which could be partially caused by differential dependence on BDNF. In parallel to activity-dependent bidirectional scaling in GAD expression, the present study further observed that a chronic change in neuronal activity leads to an alteration in neurotransmitter release from GABAergic neurons in a homeostatic, bidirectional fashion. Therefore, the differential expression of GAD65 and 67 during prolonged changes in neuronal activity may be implicated in some aspects of bidirectional homeostatic plasticity within mature GABAergic presynapses.

  19. Aging-related impairments of hippocampal mossy fibers synapses on CA3 pyramidal cells.

    Science.gov (United States)

    Villanueva-Castillo, Cindy; Tecuatl, Carolina; Herrera-López, Gabriel; Galván, Emilio J

    2017-01-01

    The network interaction between the dentate gyrus and area CA3 of the hippocampus is responsible for pattern separation, a process that underlies the formation of new memories, and which is naturally diminished in the aged brain. At the cellular level, aging is accompanied by a progression of biochemical modifications that ultimately affects its ability to generate and consolidate long-term potentiation. Although the synapse between dentate gyrus via the mossy fibers (MFs) onto CA3 neurons has been subject of extensive studies, the question of how aging affects the MF-CA3 synapse is still unsolved. Extracellular and whole-cell recordings from acute hippocampal slices of aged Wistar rats (34 ± 2 months old) show that aging is accompanied by a reduction in the interneuron-mediated inhibitory mechanisms of area CA3. Several MF-mediated forms of short-term plasticity, MF long-term potentiation and at least one of the critical signaling cascades necessary for potentiation are also compromised in the aged brain. An analysis of the spontaneous glutamatergic and gamma-aminobutyric acid-mediated currents on CA3 cells reveal a dramatic alteration in amplitude and frequency of the nonevoked events. CA3 cells also exhibited increased intrinsic excitability. Together, these results demonstrate that aging is accompanied by a decrease in the GABAergic inhibition, reduced expression of short- and long-term forms of synaptic plasticity, and increased intrinsic excitability. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Neuronal signaling modulates protein homeostasis in Caenorhabditis elegans post-synaptic muscle cells.

    Science.gov (United States)

    Garcia, Susana M; Casanueva, M Olivia; Silva, M Catarina; Amaral, Margarida D; Morimoto, Richard I

    2007-11-15

    Protein homeostasis maintains proper intracellular balance by promoting protein folding and clearance mechanisms while minimizing the stress caused by the accumulation of misfolded and damaged proteins. Chronic expression of aggregation-prone proteins is deleterious to the cell and has been linked to a wide range of conformational disorders. The molecular response to misfolded proteins is highly conserved and generally studied as a cell-autonomous process. Here, we provide evidence that neuronal signaling is an important modulator of protein homeostasis in post-synaptic muscle cells. In a forward genetic screen in Caenorhabditis elegans for enhancers of polyglutamine aggregation in muscle cells, we identified unc-30, a neuron-specific transcription factor that regulates the synthesis of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). We used additional sensors of protein conformational states to show that defective GABA signaling or increased acetylcholine (ACh) signaling causes a general imbalance in protein homeostasis in post-synaptic muscle cells. Moreover, exposure to GABA antagonists or ACh agonists has a similar effect, which reveals that toxins that act at the neuromuscular junction are potent modifiers of protein conformational disorders. These results demonstrate the importance of intercellular communication in intracellular homeostasis.

  1. High energy photon response

    International Nuclear Information System (INIS)

    Cummings, F.M.; Yoder, R.C.; Endres, G.W.R.; Kathren, R.L.

    1981-01-01

    This study examines the response of the Hanford 4-chip and 5-chip dosimeter to high energy photons. The dose response of the Hanford Multipurpose Personnel Diometer (HMPD) to photons with energies greater than 0.65 MeV has been evaluated relative to the dose produced by photons from a 60 Co. source. The penetrating dose determined with the HMPD is compared to the 1 cm depth dose in tissue measured with an extrapolation chamber. The results of the study indicate that the HMPD can be used to estimate the 1 cm depth dose in tissue from photons with energies between 0.65 MeV and 3.0 MeV to within an accuracy of 15%. However, the 1 cm depth dose is underestimated by 38% when the dosimeter is irradiated in a beam of very high energy photons produced by bombarding a tungsten target with 25 MeV electrons

  2. Dynamic alarm response procedures

    International Nuclear Information System (INIS)

    Martin, J.; Gordon, P.; Fitch, K.

    2006-01-01

    The Dynamic Alarm Response Procedure (DARP) system provides a robust, Web-based alternative to existing hard-copy alarm response procedures. This paperless system improves performance by eliminating time wasted looking up paper procedures by number, looking up plant process values and equipment and component status at graphical display or panels, and maintenance of the procedures. Because it is a Web-based system, it is platform independent. DARP's can be served from any Web server that supports CGI scripting, such as Apache R , IIS R , TclHTTPD, and others. DARP pages can be viewed in any Web browser that supports Javascript and Scalable Vector Graphics (SVG), such as Netscape R , Microsoft Internet Explorer R , Mozilla Firefox R , Opera R , and others. (authors)

  3. Responsible conduct of research

    CERN Document Server

    Shamoo, Adil E

    2015-01-01

    Since the early 2000s, the field of Responsible Conduct of Research has become widely recognized as essential to scientific education, investigation, and training. At present, research institutions with public funding are expected to have some minimal training and education in RCR for their graduate students, fellows and trainees. These institutions also are expected to have a system in place for investigating and reporting misconduct in research or violations of regulations in research with human subjects, or in their applications to federal agencies for funding. Public scrutiny of the conduct of scientific researchers remains high. Media reports of misconduct scandals, biased research, violations of human research ethics rules, and moral controversies in research occur on a weekly basis. Since the 2009 publication of the 2nd edition of Shamoo and Resnik's Responsible Conduct of Research, there has been a vast expansion in the information, knowledge, methods, and diagnosis of problems related to RCR and the ...

  4. Responsive Decision-Making

    DEFF Research Database (Denmark)

    Pedersen, Carsten Lund; Andersen, Torben Juul

    developments and feeding that information into strategic decisions will enable higher quality outcomes and better adaptive responses for persistent performance. Thus we review relevant parts of the strategic decision making literature to conceptualize the responsive decision making model and propose a study......Strategic decision making remains a focal point in the strategy field, but despite decades of rich conceptual and empirical research we still seem distant from a level of understanding that can guide corporate practices effectively under turbulent and unpredictable environmental conditions. Hence......, the aim of this study is to gain deeper insights into the complex and multifaceted decision processes that take place in large complex organizations operating in dynamic high-velocity markets. It is proposed that the ability to obtain faster, more accurate and updated insights about ongoing environmental...

  5. Aesthetic responses to music

    DEFF Research Database (Denmark)

    Istok, Eva; Brattico, Elvira; Jacobsen, Thomas

    2009-01-01

    We explored the content and structure of the cognitive, knowledge-based concept underlying aesthetic responses to music. To this aim, we asked 290 Finnish students to verbally associate the aesthetic value of music and to write down a list of appropriate adjectives within a given time limit....... No music was presented during the task. In addition, information about participants' musical background was collected. A variety of analysis techniques was used to determine the key results of our study. The adjective "beautiful" proved to be the core item of the concept under question. Interestingly......, the adjective "touching" was often listed together with "beautiful". In addition, we found music-specific vocabulary as well as adjectives related to emotions and mood states indicating that affective processes are an essential part of aesthetic responses to music. Differences between music experts and laymen...

  6. Probing human response times

    Science.gov (United States)

    Johansen, Anders

    2004-07-01

    In a recent preprint (Dialog in e-mail traffic, preprint cond-mat/0304433), the temporal dynamics of an e-mail network has been investigated by Eckmann, Moses and Sergi. Specifically, the time period between an e-mail message and its reply were recorded. It will be shown here that their data agrees quantitatively with the frame work proposed to explain a recent experiment on the response of “internauts” to a news publication (Physica A 296(3-4) (2001) 539) despite differences in communication channels, topics, time-scale and socio-economic characteristics of the two population. This suggest a generalized response time distribution ∼ t-1 for human populations in the absence of deadlines with important implications for psychological and social studies as well the study of dynamical networks.

  7. Hematologic Response to Exercise

    Directory of Open Access Journals (Sweden)

    Javier Fernando Bonilla Briceño

    2005-12-01

    Full Text Available Moderate to intensive physical exercisegenerates different types of response in an individual.These responses depend upon the typeof exercise and the duration of it, and they canbe acute or chronic. Exercise affects differentcorporal system, among those is the hematologicalsystem. Literature describes changes inthe blood volume, changes in the activity andpopulation of white blood cells, as well asmodifications in the humoral and cellularimmunity, and in the count and shape of bloodplatelets. Also and as a result of those changes, ithas been determined too, that exercise modifiesin a negative way the life time of red blood cells,generating an apparent anemia, that has beenwidely discuss and that might be, among manyfactors, associated to hemolysis. This hemolysismight be associated with osmotic mechanismsor oxidative stress. The true is that all thoseevents are strongly related and may cause a lowperformance in the practice of any physicalactivity, including that of sportsmen.

  8. Corporate Social Responsibility

    DEFF Research Database (Denmark)

    Liempd, Dennis van; Warming-Rasmussen, Bent; Abild-Nielsen, Jens

    2007-01-01

    Målet med denne artikel er at klargøre, at der findes forskellige teoretiske tilgange til ansvarlig leverandørstyring og Corporate Social Responsibility (i det følgende kaldt CSR). Endvidere er det målet at belyse, at området er i kraftig udvikling og forventes at få øget betydning for revisor i...... ansvarlig leverandørstyring og CSR. I artiklen konkluderes følgende: - at udviklingen i Corporate Social Responsibility indikerer, at etik er den mest betydende faktor (driver); (jf. afsnit 1)- at etik som primær driver vil betyde, at virksomheden vil gå ud over lovens minimumkrav, og stræbe efter de...

  9. Structural response synthesis

    Energy Technology Data Exchange (ETDEWEB)

    Ozisik, H.; Keltie, R.F.

    1988-12-01

    The open loop control technique of predicting a conditioned input signal based on a specified output response for a second order system has been analyzed both analytically and numerically to gain a firm understanding of the method. Differences between this method of control and digital closed loop control using pole cancellation were investigated as a follow up to previous experimental work. Application of the technique to diamond turning using a fast tool is also discussed.

  10. Cell response to surgery.

    LENUS (Irish Health Repository)

    Ni Choileain, Niamh

    2012-02-03

    OBJECTIVES: To describe the profound alterations in host immunity that are produced by major surgery as demonstrated by experimental and clinical studies, and to evaluate the benefits of therapeutic strategies aimed at attenuating perioperative immune dysfunction. DATA SOURCES: A review of the English-language literature was conducted, incorporating searches of the MEDLINE, EMBASE, and Cochrane collaboration databases to identify laboratory and clinical studies investigating the cellular response to surgery. STUDY SELECTION: Original articles and case reports describing immune dysfunction secondary to surgical trauma were included. DATA EXTRACTION: The results were compiled to show outcomes of different studies and were compared. DATA SYNTHESIS: Current evidence indicates that the early systemic inflammatory response syndrome observed after major surgery that is characterized by proinflammatory cytokine release, microcirculatory disturbance, and cell-mediated immune dysfunction is followed by a compensatory anti-inflammatory response syndrome, which predisposes the patient to opportunistic infection, multiple organ dysfunction syndrome, and death. Because there are currently no effective treatment options for multiple organ dysfunction syndrome, measures to prevent its onset should be initiated at an early stage. Accumulating experimental evidence suggests that targeted therapeutic strategies involving immunomodulatory agents such as interferon gamma, granulocyte colony-stimulating factor, the prostaglandin E(2) antagonist, indomethacin, and pentoxifylline may be used for the treatment of systemic inflammatory response syndrome to prevent the onset of multiple organ dysfunction syndrome. CONCLUSIONS: Surgical trauma produces profound immunological dysfunction. Therapeutic strategies directed at restoring immune homeostasis should aim to redress the physiological proinflammatory-anti-inflammatory cell imbalance associated with major surgery.

  11. Quantal Response: Nonparametric Modeling

    Science.gov (United States)

    2017-01-01

    determines the response via y =   0, x < L 1, x > L . (1) If L is known and constant, then y is a step function of x with jump at x = L...therein as “Results of 69 Ballistic Shots on Phase II Al2O3/Kevlar Armor Plates”, although there are only 68 data points in the report. Chang and Bodt

  12. Strategic Corporate Social Responsibility

    OpenAIRE

    Planer-Friedrich, Lisa; Sahm, Marco

    2017-01-01

    We examine the strategic use of Corporate Social Responsibility (CSR) in imperfectly competitive markets. The level of CSR determines the weight a firm puts on consumer surplus in its objective function before it decides upon supply. First, we consider symmetric Cournot competition and show that the endogenous level of CSR is positive for any given number of firms. However, positive CSR levels imply smaller equilibrium profits. Second, we find that an incumbent monopolist can use CSR as an en...

  13. Conceptualising environmental responsibility

    International Nuclear Information System (INIS)

    Lenzen, Manfred; Murray, Joy

    2010-01-01

    Downstream responsibility is rarely addressed in the academic literature and in corporate sustainability reporting. We conceptualise downstream responsibility for the example of carbon emissions, by establishing a terminology as well as a framework for quantifying downstream carbon footprints. By extracting emissions-intensive sales chains for a number of Australian industry sectors, and comparing these to emissions-intensive supply chains, we demonstrated the ability of input-output analysis to quantify emissions responsibility in both directions. We extend the definition of downstream responsibility beyond the product use and disposal phases, to include what we call 'enabled' emissions. This term implies that whatever is sold downstream enables our customers to operate and emit, irrespective of whether it is our product that is combusted, or that directly combusts fuels, or not. Our structural path analyses and threshold-capture relationships reveal stark differences between industries with regard to the data collection efforts necessary to achieve a reasonably complete footprint assessment. Industries appear to have their own specific carbon footprint profiles, and one cannot design generic relevance tests that tell which data to collect. Moreover we conclude that current completeness standards in carbon reporting cannot be satisfied using relevance thresholds. Input-output analysis and structural path analysis are excellent tools that can help companies undertake screening exercises, which in turn help prioritising and streamlining the collection of data needed to establish a corporate downstream carbon footprint. Compared to conventional manual approaches, hybrid life-cycle assessments assisted by input-output analysis and structural path analysis achieve more complete results, with substantially less staff, money and time. (author)

  14. RELIGIOUS RESPONSES TO GLOBALISATION

    Directory of Open Access Journals (Sweden)

    Hatib A. Kadir

    2011-08-01

    Full Text Available Sociological discussion of globalisation is preoccupied with the political, economic, and military dimension of it, with little attention to its religious aspect. This paper attempts to trace the impacts of globalisation on religion and religious responses, the argument of which derives mainly from the so-called “Bridge-Building Program” organised by CRCS & ICRS-UGM in 2008. It argues that though they share a common concern, people of different faiths are at risk of deepening the problems rather than offering solutions in view of their different responses for which we categorise them into different but overlapping categories -ideological, ambivalent, integrative, exclusive, and imitative. It then leads to a more fundamental question of whether interfaith cooperation is possible given those different and sometime opposing responses. [Dalam kajian sosiologi, diskusi mengenai globalisasi kerap kali semata-mata ditinjau dari sisi politik, enonomi dan militer, sementara dimensi agama sering kali dikesampingkan. Artikel ini membahas dampak globalisasi terhadap agama dan respon komunitas agama terhadap globalisasi. Data yang muncul dalam artikel ini diambil dari sebuah workshop berjudul“Bridge- Building Program.” Melalui artikel ini, saya berpendapat bahwa, meskikomunitas agama-agama memiliki keprihatinan yang sama terhadap dampak globalisasi, namun respon mereka cenderung mempertajam persoalan yang diakibatkan globalisasi, ketimbang memberikan solusi. Respon tersebut dalam dikategorikan –meski tidak kaku- dalam: respon ideologis, ambivalen, integratif, ekslusif dan imitatif. Selanjutnya, artikel juga mengulas pada pertanyaan mendasar mengenai apakah kerjasama antar agama mungkin dilakukan menyimak ragam respon yang saling bertentangan tersebut.

  15. Load responsive hydrodynamic bearing

    Science.gov (United States)

    Kalsi, Manmohan S.; Somogyi, Dezso; Dietle, Lannie L.

    2002-01-01

    A load responsive hydrodynamic bearing is provided in the form of a thrust bearing or journal bearing for supporting, guiding and lubricating a relatively rotatable member to minimize wear thereof responsive to relative rotation under severe load. In the space between spaced relatively rotatable members and in the presence of a liquid or grease lubricant, one or more continuous ring shaped integral generally circular bearing bodies each define at least one dynamic surface and a plurality of support regions. Each of the support regions defines a static surface which is oriented in generally opposed relation with the dynamic surface for contact with one of the relatively rotatable members. A plurality of flexing regions are defined by the generally circular body of the bearing and are integral with and located between adjacent support regions. Each of the flexing regions has a first beam-like element being connected by an integral flexible hinge with one of the support regions and a second beam-like element having an integral flexible hinge connection with an adjacent support region. A least one local weakening geometry of the flexing region is located intermediate the first and second beam-like elements. In response to application of load from one of the relatively rotatable elements to the bearing, the beam-like elements and the local weakening geometry become flexed, causing the dynamic surface to deform and establish a hydrodynamic geometry for wedging lubricant into the dynamic interface.

  16. Ontario demand response scenarios

    International Nuclear Information System (INIS)

    Rowlands, I.H.

    2005-09-01

    Strategies for demand management in Ontario were examined via 2 scenarios for a commercial/institutional building with a normal summertime peak load of 300 kW between 14:00 and 18:00 during a period of high electricity demand and high electricity prices. The first scenario involved the deployment of a 150 kW on-site generator fuelled by either diesel or natural gas. The second scenario involved curtailing load by 60 kW during the same periods. Costs and benefits of both scenarios were evaluated for 3 groups: consumers, system operators and society. Benefits included electricity cost savings, deferred transmission capacity development, lower system prices for electricity, as well as environmental changes, economic development, and a greater sense of corporate social responsibility. It was noted that while significant benefits were observed for all 3 groups, they were not substantial enough to encourage action, as the savings arising from deferred generation capacity development do not accrue to individual players. The largest potential benefit was identified as lower prices, spread across all users of electricity in Ontario. It was recommended that representative bodies cooperate so that the system-wide benefits can be reaped. It was noted that if 10 municipal utilities were able to have 250 commercial or institutional customers engaged in distributed response, then a total peak demand reduction of 375 MW could be achieved, representing more than 25 per cent of Ontario's target for energy conservation. It was concluded that demand response often involves the investment of capital and new on-site procedures, which may affect reactions to various incentives. 78 refs., 10 tabs., 5 figs

  17. Community response to noise

    Directory of Open Access Journals (Sweden)

    Takashi Yano

    2012-01-01

    Full Text Available Activities from 2008 to 2011 by ICBEN community response to noise team were summarized. That is, individual community-based indexes such as community tolerance Level, Zuricher Fluglarm Index (ZFI and Frankfurter Fluglarm Index (FFI/FNI were newly proposed, differences in railway bonus between Europe and Asia were discussed by a Swedish survey, socio-acoustic surveys were reported from developing countries, and annoyance equivalents and dominant source models were proposed as the adequate combined noise model. Furthermore, not only negative, but also positive aspects of sound were discussed as soundscape studies. Finally, seven items were listed as future team activities.

  18. Realizing Corporate Responsibility

    DEFF Research Database (Denmark)

    Girschik, Verena

    pharmaceutical company Novo Nordisk, a company known for its remarkable investments in integrating societal objectives into its business model and promoting new ways of thinking about and doing business. The case inspired the overarching theoretical question how actors construct and legitimize new ideas...... and practices at the nascent stages of institutional change. To address this question, the dissertation develops a micro-sociological approach to institutional change that brings to light how actors struggle over meaning in power relations by focusing on processes of positioning and framing. The three articles...... in this dissertation unfold distinct yet interdependent processes of positioning and framing that constitute new ways of performing and understanding corporate responsibility....

  19. Individualizing Services, Individualizing Responsibility

    DEFF Research Database (Denmark)

    Garsten, Christina; Hollertz, Katarina; Jacobsson, Kerstin

    and responsibilising the unemployed individual? The paper finds that the individualisation that is taking place occurs as an individualisation of responsibility, more than as an individualisation of interventions. A related finding is that the social rights perspective is becoming performance......The paper focuses on the unemployed individual and her position in local activation practice. The overall aim is to analyse the role of individualisation of local activation policy in the construction of social citizenship in Sweden. More specifically, we ask: To what extent do clients have...... at local level in one Swedish municipality....

  20. Disaster Response: Improving Effectiveness

    Science.gov (United States)

    2007-12-01

    Canter . 26 July 2006. 1. 10 Thomas A Garrett and Russell S. Sobel. “The political Economy of FEMA Disaster Payments.” The Federal Bank of St. Louis...and, Brownie, you’re doing a heck of a job. The FEMA Director is working 24…they’re working 24 hours a day.”19 David McEntire highlights the...releases/2005/09/20050902-2.html. Last accessed 9 November 2007. 20 David A. McEntire. Disaster Response and Recovery: Strategies and Tactics for

  1. Affect and criminal responsibility

    Directory of Open Access Journals (Sweden)

    Drakić Dragiša S.

    2017-01-01

    Full Text Available In this article the author deals with an issue of relationship between the affect and criminal responsibility. In order to provide a multi-angle approach to analysis of this issue the author resorted to multidisciplinary - criminal law and psychiatric-psychological approach. Although the topic covered by this article is significant and complex, it appears to be of virtually no interest in the literature. For that reason the author's endeavor to research this topic should not go unmentioned. In the first part of the article the author tried to provide answers to some preliminary questions without which it would be impossible to understand the relationship between the affect and criminal responsibility. Those are the following questions: what are affects, what is their nature and intensity, how long they last and how they influence psychological functions of a person acting in affect? Central part of the article is dedicated to examining the importance of the affect as a phenomenon in criminal law dogma and in judicial rulings, as well as its effect on criminal responsibility. The author finds that acting in affect may be considered as a mitigating circumstance in the sentencing, but can also be a basis for mitigation of the sentence or even suspension of the sentence, as part of some general criminal law norms. Also, for certain offenses it may be considered as a favorable condition that renders that offence to be less grave. Finally, the affect may be considered as a psychological basis diminished, or even lack of, mental capacity. The last above mentioned issue receives special attention of the author, and claims that only the affect that is 'of extreme proportions' may lead to mental incapacity. Such affect is the one that 'demolishes restrains and removes reasonable and target-oriented actions'. In further analysis the author proposes criteria and methodology for assessment of person's sanity in criminal law and criminal procedure. Further

  2. The Chronic Responsibility

    DEFF Research Database (Denmark)

    Ravn, Iben M; Frederiksen, Kirsten; Beedholm, Kirsten

    2016-01-01

    behavior to be the main factors influencing susceptibility to chronic diseases. We argue that this discursive construction naturalizes a division between people who can actively manage responsible self-care and those who cannot. Such discourses may serve the interests of those patients who are already......This article reports on the results of a Fairclough-inspired critical discourse analysis aiming to clarify how chronically ill patients are presented in contemporary Danish chronic care policies. Drawing on Fairclough’s three-dimensional framework for analyzing discourse, and using Dean’s concepts...

  3. Responsive City Lighting

    DEFF Research Database (Denmark)

    Poulsen, Esben Skouboe; Andersen, Hans Jørgen; Jensen, Ole B.

    This paper presents and discusses perspectives extracted from two interviews conducted during the experiments Urban Responsive Lighting. The two experts embody two different fields related to city lighting: architecture & public lighting industry. The representatives were invited to the test......-site, where 15 LED RGB Park lamps, controlled driven by a wind sensor, mobile phone applications or by thermal camera tracking. According to the specialists are the social and aesthetical dimensions more interesting than the energy use cases and efficiency. This motivates an interdisciplinary discussion...

  4. State responses to biotechnology.

    Science.gov (United States)

    Harris, Rebecca C

    2015-01-01

    This article reviews biotechnology legislation in the 50 states for 11 policy areas spanning 1990-2010, an era of immense growth in biotechnology, genetic knowledge, and significant policy development. Policies regarding health insurance, life insurance, long-term care insurance, DNA data bank collection, biotech research protection, biotech promotion and support, employment discrimination, genetic counselor licensing, human cloning, and genetic privacy each represent major policy responses arising from biotechnology and coinciding with key areas of state regulation (insurance, criminal justice, economic development, labor law, health and safety, privacy, and property rights). This analysis seeks to answer three questions regarding biotechnology legislation at the state level: who is acting (policy adoption), when is policy adopted (policy timing), and what is policy doing (policy content). Theoretical concerns examine state ideology (conservative or liberal), policy type (economic or moral), and the role of external events (federal law, news events, etc.) on state policy adoption. Findings suggest ideological patterns in adoption, timing, and content of biotech policy. Findings also suggest economic policies tend to be more uniform in content than moral policies, and findings also document a clear link between federal policy development, external events, and state policy response.

  5. Seizmic response spectra

    Directory of Open Access Journals (Sweden)

    Igor Leššo

    2005-12-01

    Full Text Available A computation of 1D and 3D seismic motion parameters was made and the influence of input parameters on these parameters were analysed. A modelling was realised on the examples of sedimentary structures geotechnical models. This comparison provides different spectral and frequencial values and spectral accelerations. The differences in seismic response spectra are influenced not only by properties of geological structures but also by the methodics of the soil structure interaction modeling and input time history spectral composition. However, the influence of geotechnical properties of geological structures on the output results are apparent. The modelling results of different input time history spectral composition, the Ricker impuls and the Gabor function were compared. In the area of cement factory in Rohožník, the new rotary kiln furnance is planned to be build. In the sense of STN 73 0036 the expert seismic judgment has been claimed. The standard and local seismic response spectra is computed for the place where the rotary kiln will be situated. The application of the local spectral acceleration in seismic load computations enables to save costs in comparing with the standard acceleration.

  6. Skeletal responses to spaceflight

    Science.gov (United States)

    Morey-Holton, Emily; Arnaud, Sara B.

    1991-01-01

    The role of gravity in the determination of bone structure is elucidated by observations in adult humans and juvenile animals during spaceflight. The primary response of bone tissue to microgravity is at the interface of the mineral and matrix in the process of biomineralization. This response is manifested by demineralization or retarded growth in some regions of the skeleton and hypermineralization in others. The most pronounced effects are seen in the heelbone and skull, the most distally located bones relative to the heart. Ground based flight simulation models that focus on changes in bone structure at the molecular, organ, and whole body levels are described and compared to flight results. On Earth, the morphologic and compositional changes in the unloaded bones are very similar to changes during flight; however, the ground based changes appear to be more transient. In addition, a redistribution of bone mineral in gravity-dependent bones occurs both in space and during head down positioning on Earth. Longitudinal data provided considerable information on the influence of endocrine and muscular changes on bone structure after unloading.

  7. Exercise Responses after Inactivity

    Science.gov (United States)

    Convertino, Victor A.

    1986-01-01

    The exercise response after bed rest inactivity is a reduction in the physical work capacity and is manifested by significant decreases in oxygen uptake. The magnitude of decrease in maximal oxygen intake V(dot)O2max is related to the duration of confinement and the pre-bed-rest level of aerobic fitness; these relationships are relatively independent of age and gender. The reduced exercise performance and V(dot)O2max following bed rest are associated with various physiological adaptations including reductions in blood volume, submaximal and maximal stroke volume, maximal cardiac output, sceletal muscle tone and strength, and aerobic enzyme capacities, as well as increases in venous compliance and submaximal and maximal heart rate. This reduction in physiological capacity can be partially restored by specific countermeasures that provide regular muscular activity or orhtostatic stress or both during the bed rest exposure. The understanding of these physiological and physical responses to exercise following bed rest inactivity has important implications for the solution to safety and health problems that arise in clinical medicine, aerospace medicine, sedentary living, and aging.

  8. Emotional response to advertising

    Directory of Open Access Journals (Sweden)

    Bogdan Anastasiei

    2014-11-01

    Full Text Available Emotions can transcend cultural, linguistic, demographic, and social boundaries. Emotions affect information processing and create a positive attitude toward the ad, which becomes associated with the brand. Objectives. This study investigates the role of pleasure (P, arousal (A and domination (D emotions in mobile’s photo camera advertisement and how each of them is influencing consumer attitude towards the advertisement and brand. Prior Work. Holbrook and Batra (1987 developed their own emotional scale based on these three dimensions (PAD, showing that these emotions mediate consumer responses to advertising. Approach. A 1*4 factorial experiment design method was adopted in order to measure the impact of independent variables (emotion type on dependent variables (attitude toward ad, attitude toward brand. Results. The results revealed that emotions like Pleasure (loving, friendly, grateful and Arousal (active, interested, excited, entertained influence consumers' attitudes towards brand and advertising. Value. Marketers need to understand the role of pleasure and arousal emotions when making advertising campaign; an effective promotion leads to persuading consumers. The results indicate that marketing practitioners should measure affective responses when testing an advertisement, as long as this action would predict brand attitude.

  9. Multilevel corporate environmental responsibility.

    Science.gov (United States)

    Karassin, Orr; Bar-Haim, Aviad

    2016-12-01

    The multilevel empirical study of the antecedents of corporate social responsibility (CSR) has been identified as "the first knowledge gap" in CSR research. Based on an extensive literature review, the present study outlines a conceptual multilevel model of CSR, then designs and empirically validates an operational multilevel model of the principal driving factors affecting corporate environmental responsibility (CER), as a measure of CSR. Both conceptual and operational models incorporate three levels of analysis: institutional, organizational, and individual. The multilevel nature of the design allows for the assessment of the relative importance of the levels and of their components in the achievement of CER. Unweighted least squares (ULS) regression analysis reveals that the institutional-level variables have medium relationships with CER, some variables having a negative effect. The organizational level is revealed as having strong and positive significant relationships with CER, with organizational culture and managers' attitudes and behaviors as significant driving forces. The study demonstrates the importance of multilevel analysis in improving the understanding of CSR drivers, relative to single level models, even if the significance of specific drivers and levels may vary by context. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Playful Hyper Responsibility: Toward a Dislocation of Parents' Responsibility?

    Science.gov (United States)

    Knudsen, Hanne; Andersen, Niels Åkerstrøm

    2014-01-01

    Over the past 10-15?years, state-funded schools have begun to require parents to assume an undefined and infinite personal responsibility. In this article, we investigate how schools organize responsibility games to respond to this challenge and how these games affect the concept of responsibility. We point to a dislocation in the way parents are…

  11. Hanford Emergency Response Plan

    International Nuclear Information System (INIS)

    Wagoner, J.D.

    1994-04-01

    The Hanford Emergency Response Plan for the US Department of Energy (DOE), Richland Operations Office (RL), incorporates into one document an overview of the emergency management program for the Hanford Site. The program has been developed in accordance with DOE orders, and state and federal regulations to protect worker and public health and safety and the environment in the event of an emergency at or affecting the Hanford Site. This plan provides a description of how the Hanford Site will implement the provisions of DOE 5500 series and other applicable Orders in terms of overall policies and concept of operations. It should be used as the basis, along with DOE Orders, for the development of specific contractor and RL implementing procedures

  12. Responsible technology acceptance

    DEFF Research Database (Denmark)

    Toft, Madeleine Broman; Schuitema, Geertje; Thøgersen, John

    2014-01-01

    on private consumers’ acceptance of having Smart Grid technology installed in their home. We analyse acceptance in a combined framework of the Technology Acceptance Model and the Norm Activation Model. We propose that individuals are only likely to accept Smart Grid technology if they assess usefulness......As a response to climate change and the desire to gain independence from imported fossil fuels, there is a pressure to increase the proportion of electricity from renewable sources which is one of the reasons why electricity grids are currently being turned into Smart Grids. In this paper, we focus...... in terms of a positive impact for society and the environment. Therefore, we expect that Smart Grid technology acceptance can be better explained when the well-known technology acceptance parameters included in the Technology Acceptance Model are supplemented by moral norms as suggested by the Norm...

  13. Corporate Social Responsibility

    DEFF Research Database (Denmark)

    Kampf, Constance

    2007-01-01

    Understanding Corporate Social Responsibility (CSR) as having explicit policies and implicit norms situated in cultural systems highlights the connections between institutional and cultural structures of nation states and business' commitment to CSR as reflected in the strategies used...... to communicate CSR to public audiences via the Internet.  To frame CSR from a situated perspective (Matten & Moon 2005) implies a shift in understanding relations between corporations and their stakeholders from a corporate-centered model to a cultural systems perspective.  This paper describes an approach...... to cultural systems in which can be used to frame our understanding of implicit norms with respect to CSR, and demonstrates how these norms result in different practices of communicating CSR in the WalMart and Maersk corporate websites....

  14. Responsive acoustic surfaces

    DEFF Research Database (Denmark)

    Peters, Brady; Tamke, Martin; Nielsen, Stig Anton

    2011-01-01

    Acoustic performance is defined by the parameter of reverberation time; however, this does not capture the acoustic experience in some types of open plan spaces. As many working and learning activities now take place in open plan spaces, it is important to be able to understand and design...... for the acoustic conditions of these spaces. This paper describes an experimental research project that studied the design processes necessary to design for sound. A responsive acoustic surface was designed, fabricated and tested. This acoustic surface was designed to create specific sonic effects. The design...... was simulated using custom integrated acoustic software and also using Odeon acoustic analysis software. The research demonstrates a method for designing space- and sound-defining surfaces, defines the concept of acoustic subspace, and suggests some new parameters for defining acoustic subspaces....

  15. Magnetically responsive enzyme powders

    Science.gov (United States)

    Pospiskova, Kristyna; Safarik, Ivo

    2015-04-01

    Powdered enzymes were transformed into their insoluble magnetic derivatives retaining their catalytic activity. Enzyme powders (e.g., trypsin and lipase) were suspended in various liquid media not allowing their solubilization (e.g., saturated ammonium sulfate and highly concentrated polyethylene glycol solutions, ethanol, methanol, 2-propanol) and subsequently cross-linked with glutaraldehyde. Magnetic modification was successfully performed at low temperature in a freezer (-20 °C) using magnetic iron oxides nano- and microparticles prepared by microwave-assisted synthesis from ferrous sulfate. Magnetized cross-linked enzyme powders were stable at least for two months in water suspension without leakage of fixed magnetic particles. Operational stability of magnetically responsive enzymes during eight repeated reaction cycles was generally without loss of enzyme activity. Separation of magnetically modified cross-linked powdered enzymes from reaction mixtures was significantly simplified due to their magnetic properties.

  16. Data Rights and Responsibilities

    Science.gov (United States)

    Wyndham, Jessica M.

    2015-01-01

    A human-rights-based analysis can be a useful tool for the scientific community and policy makers as they develop codes of conduct, harmonized standards, and national policies for data sharing. The human rights framework provides a shared set of values and norms across borders, defines rights and responsibilities of various actors involved in data sharing, addresses the potential harms as well as the benefits of data sharing, and offers a framework for balancing competing values. The right to enjoy the benefits of scientific progress and its applications offers a particularly helpful lens through which to view data as both a tool of scientific inquiry to which access is vital and as a product of science from which everyone should benefit. PMID:26297755

  17. Responses to natural disasters

    Science.gov (United States)

    Maggs, William Ward

    Since 1964, natural disasters caused by earthquakes, volcanic eruptions, or extreme weather in the form of floods, droughts, or hurricanes, have been responsible for more than 2,756,000 deaths worldwide in nations other than the United States, the Soviet Union, and the Eastern European Bloc, according to figures tabulated by the Office of Foreign Disaster Assistance (OFDA) of the Agency for International Development (AID). Over 95% of these fatalities occurred in developing or third world countries. Damage resulting from these calamities has been severe but extremely difficult to estimate in monetary terms. In 1986, U.S. government and voluntary agencies spent $303 million on natural disaster assistance around the world, 79% of total world assistance. In 1985 the U.S. total was nearly $900 million, 48% of the $1.84 billion world total.

  18. Thermal Responsive Envelope

    DEFF Research Database (Denmark)

    Foged, Isak Worre; Pasold, Anke

    2015-01-01

    The paper presents an architectural computational method and model, which, through additive and subtractive processes, create composite elements with bending behaviour based on thermal variations in the surrounding climatic environment. The present effort is focused on the manipulation of assembly...... composite layers and their relative layer lengths thereby embedding the merged material effect to create a responsive behavioural architectural envelope. Copper and polypropylene are used as base materials for the composite structure due to their high differences in thermal expansion, surface emissivity...... alterations, their respective durability and copper’s architectural (visual and transformative) aesthetic qualities. Through the use of an evolutionary solver, the composite structure of the elements are organised to find the bending behaviour specified by and for the thermal environments. The entire model...

  19. Inflammatory response after nailing.

    Science.gov (United States)

    Kanakaris, Nikolaos K; Anthony, Christopher; Papasotiriou, Antonios; Giannoudis, Peter V

    2017-06-01

    Intramedullary nailing, as the gold standard stabilisation method of most long bones, has been tailed by its extensive use as the basic tool of investigating the immune response to trauma in many large and small animal models, as well as at the clinical setting. Over the last few decades a complex map of interactions between pro and anti-inflammatory pathways has been the result of these significant global research efforts. Parallel to the evolution of modern nailing and reaming techniques, significant developments at the fields of other disciplines relevant to trauma care, has improved the contemporary management of injured patients, challenging previous concepts and altering clinical barriers. The current article aims to summarise the current understanding of the effect of instrumenting the medullary canal after trauma, and hint on potential future directions. Copyright © 2017. Published by Elsevier Ltd.

  20. Hanford Emergency Response Plan

    Energy Technology Data Exchange (ETDEWEB)

    Wagoner, J.D.

    1994-04-01

    The Hanford Emergency Response Plan for the US Department of Energy (DOE), Richland Operations Office (RL), incorporates into one document an overview of the emergency management program for the Hanford Site. The program has been developed in accordance with DOE orders, and state and federal regulations to protect worker and public health and safety and the environment in the event of an emergency at or affecting the Hanford Site. This plan provides a description of how the Hanford Site will implement the provisions of DOE 5500 series and other applicable Orders in terms of overall policies and concept of operations. It should be used as the basis, along with DOE Orders, for the development of specific contractor and RL implementing procedures.

  1. Gut Bacteria Affect Immunotherapy Response

    Science.gov (United States)

    Three new studies have identified intestinal bacteria that appear to influence the response to checkpoint inhibitors. This Cancer Currents blog post explains how the researchers think their findings could be used to improve patients’ responses to these immunotherapy drugs.

  2. Successful oil spill response

    International Nuclear Information System (INIS)

    Tost, J.

    2000-01-01

    A freighter in the process of loading rock for the Quebec Iron and Titanium Mining Company near Havre-St. Pierre on the extreme north shore of the St. Lawrence River, was suddenly tossed against the dock by rough waters on the night of March 23, 1999, and spilled 49 tonnes of bunker fuel oil into the river. This article describes how the crew of the ship, trained by Environmental Accident Protection Inc., based in Petrolia, Ontario, averted disaster by responding to the accident quickly and effectively. Their first action was to notify the appropriate environmental and regulatory authorities and to put in place containment booms which corralled about 17 tonnes of oil. The oil contained by the booms were removed by trained personnel under the guidance of Eastern Canada Response Corporation of Corunna, Ontario, and Response Systems Inc. of Neshanic, New Jersey, in approximately three hours with only minimum disruption to the environment. Further cleanup of the area, often hindered by bad weather, freezing rain, ice, and 100 km/hr winds, was done by the cooperative efforts of governments, industry and the local fishermen's association. The work included scrubbing the shore with wire brushes and scrapers and handbathing some 1000 migratory birds. The cleanup job was completed in about three weeks and the Mingan Archipelago National Park Reserve and other nearby habitats for migrating birds were saved the devastation that would have occurred, except for the quick and knowledgeable intervention of a trained crew and an outstanding example of public-private sector and community cooperation. 2 photos

  3. Affective responses to dance.

    Science.gov (United States)

    Christensen, Julia F; Pollick, Frank E; Lambrechts, Anna; Gomila, Antoni

    2016-07-01

    The objective of the present work was the characterization of mechanisms by which affective experiences are elicited in observers when watching dance movements. A total of 203 dance stimuli from a normed stimuli library were used in a series of independent experiments. The following measures were obtained: (i) subjective measures of 97 dance-naïve participants' affective responses (Likert scale ratings, interviews); and (ii) objective measures of the physical parameters of the stimuli (motion energy, luminance), and of the movements represented in the stimuli (roundedness, impressiveness). Results showed that (i) participants' ratings of felt and perceived affect differed, (ii) felt and perceived valence but not arousal ratings correlated with physical parameters of the stimuli (motion energy and luminance), (iii) roundedness in posture shape was related to the experience of more positive emotion than edgy shapes (1 of 3 assessed rounded shapes showed a clear effect on positiveness ratings while a second reached trend level significance), (iv) more impressive movements resulted in more positive affective responses, (v) dance triggered affective experiences through the imagery and autobiographical memories it elicited in some people, and (vi) the physical parameters of the video stimuli correlated only weakly and negatively with the aesthetics ratings of beauty, liking and interest. The novelty of the present approach was twofold; (i) the assessment of multiple affect-inducing mechanisms, and (ii) the use of one single normed stimulus set. The results from this approach lend support to both previous and present findings. Results are discussed with regards to current literature in the field of empirical aesthetics and affective neuroscience. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Psychophysiological Responses to Salsa Dance

    OpenAIRE

    Guidetti, Laura; Buzzachera, Cosme Franklim; Emerenziani, Gian Pietro; Meucci, Marco; Saavedra, Francisco; Gallotta, Maria Chiara; Baldari, Carlo

    2015-01-01

    Speculation exists whether dance provides physiological stimuli adequate to promote health and fitness benefits. Unfortunately, research to date has not addressed the affective and exertional responses to dance. These responses are of interest as positive affective and exertional responses experienced during physical activity may play an important role in predicting adherence. The present study aims to examine the psychophysiological responses of different Salsa dance styles. Ten pairs of dan...

  5. The systemic inflammatory response syndrome.

    Science.gov (United States)

    Robertson, Charles M; Coopersmith, Craig M

    2006-04-01

    The systemic inflammatory response syndrome (SIRS) is the body's response to an infectious or noninfectious insult. Although the definition of SIRS refers to it as an "inflammatory" response, it actually has pro- and anti-inflammatory components. This review outlines the pathophysiology of SIRS and highlights potential targets for future therapeutic intervention in patients with this complex entity.

  6. Social Facilitation of Aiding Responses.

    Science.gov (United States)

    Bartell, Patricia; And Others

    Research on individual's response to emergency situations in the presence of others has produced conflicting results. The bystander effect is the label applied to inaction or the unlikelihood of assistance with others present. The social facilitation effect occurs when the presence of others energizes response; strong habit responses are…

  7. Corporate social responsibility in Islam

    OpenAIRE

    Elasrag, Hussein

    2015-01-01

    The aim of this study is to review the Islamic principles of CSR, and the definition of a structured social corporate responsibility (CSR), and based on this responsibility. And provide a practical through the international financial institutions that can implement CSR policies framework. This study provides the basis of social responsibilities that apply to those derived from divine sources of international financial institutions.

  8. Corporate social responsibility in hospitality

    Directory of Open Access Journals (Sweden)

    Snježana Gagić

    2016-01-01

    Full Text Available Responsible management of global hospitality companies increasingly recognizes how important are concerns about the society, the environment as well as all stakeholders in maintaining a good market position. In Serbia, the concept of corporate social responsibility is relatively unknown and insufficiently researched in all business areas, especially in the hospitality industry where small businesses are dominated. The papers task is to present particular activities that demonstrate social responsibility to employees, customers-guests, local communities as well as the environment. The paper aims to highlight the benefits of adopting the principles of corporate social responsibility and innovation applied in catering enterprises as an example of good corporate social responsibility practices.

  9. Spill response exercises and lessons learned : a response organization's perspective

    International Nuclear Information System (INIS)

    Taylor, E.; Green, M.

    2001-01-01

    In the past five years, Burrard Clean Operations (BCO) has demonstrated its' oil spill response capabilities through different types of exercises. Such exercises are necessary for certification of Response Organizations in Canada. The exercises can be performed through actual response to spills or through simulated situations. Both can provide an opportunity to practice different levels of response to a range of conditions in various settings. They also provide the opportunity to focus on specific themes that can be part of a response and to identify areas for improvement in response actions. They also make it possible to interface with government agencies, industry and others that participate in spill responses. The exercise program for BCO is aimed at maintaining certification and to assist the Canadian Coast Guard. The exercises broaden the lessons learned and set a course for future enhancement to spill readiness should a real incident occur. The goals of the exercise program are to provide real time drills that show the operational capability of a representative sample of BCO equipment, management and trained spill responders. The response functions of the BCO exercise program are: notification, response organization activation, contractor activation, situation analysis, strategy development for marine oil spill response, site safety, equipment deployment, containment, recovery, shoreline assessment, cleanup, communications, decontamination, logistics, and financial management. The BCO experience has led to the basic conclusions that there is a need to vary the exercise design and format and that there is a need to implement follow-up actions provided during exercise evaluations. 7 refs., 3 tabs

  10. Marine oil spill response organizations

    International Nuclear Information System (INIS)

    Hendry, C.

    1997-01-01

    The obligations under the law relative to the prevention of marine oil spills and the type of emergency plans needed to mitigate any adverse effects caused by a marine oil spill were discussed. The organizational structure, spill response resources and operational management capabilities of Canada's newly created Response Organizations (ROs) were described. The overall range of oil spill response services that the RO provides to the domestic oil handling, oil transportation and the international shipping industries were reviewed. Amendments to the Canada Shipping Act which require that certain ships and oil handling facilities take oil spill preparedness and response measures, including having an arrangement with an RO certified by the Canadian Coast Guard, were outlined. Canadians now benefit from five ROs established to provide coast-to-coast oil spill response coverage. These include the Western Canada Marine Response Corporation, the Canadian Marine Response Management Corporation, the Great Lakes Response Corporation, the Eastern Canada Response Corporation and the Atlantic Emergency Response Team Ltd. ROs have the expertise necessary to organize and manage marine oil spill response services. They can provide equipment, personnel and operational management for the containment, recovery and cleanup of oil spilled on water

  11. Why Pandemic Response is Unique

    DEFF Research Database (Denmark)

    Bækkeskov, Erik; Rubin, Olivier

    2014-01-01

    attention and coverage in two deviant cases, the USA and Denmark. Findings – Theories linking political survival to disaster responses find little empirical support in the substantial cross-country variations of vaccination responses during the 2009 H1N1 pandemic. Rather than following a political logic......, the case studies of media coverage in the USA and Denmark demonstrate that the response was bureaucratized in the public health agencies (CDC and DMHA, respectively). Hence, while natural disaster responses appear to follow a political logic, the response to pandemics appears to be more strongly instituted...... in the hands of bureaucratic experts. Research limitations/implications – There is an added value of encompassing bureaucratic dynamics in political theories of disaster response; bureaucratized expertise proved to constitute a strong plausible explanation of the 2009 pandemic vaccination response. Practical...

  12. Social Economy and Responsibility

    Directory of Open Access Journals (Sweden)

    Eva Abramuszkinová Pavlíková

    2012-01-01

    Full Text Available Given the importance of entrepreneurial activities as an engine of economic growth and poverty alleviation, the issue of business development and entrepreneurial activities, has received increasing attention from a number of interested parties worldwide and also in the Czech Republic. The focus of this paper is on a social economy, a social responsibility and social enterprises. The development of the social economy framework will be introduced in the European context and specifically in the Czech Republic. A case study of a Czech social entrepreneur will be introduced based on qualitative research, namely the biographical narrative method.Social enterprises can support activities of various target groups, such as economic activities of mentally and physically handicapped people, which often operate in economically and socially marginalized situations, including stereotyped images. They give them a chance to become active members of society. In this way they can help to reduce the poverty on a local level. The aim of this paper is to introduce a social entrepreneurship as important part of social economy development in the Czech Republic.

  13. Vaccines, our shared responsibility.

    Science.gov (United States)

    Pagliusi, Sonia; Jain, Rishabh; Suri, Rajinder Kumar

    2015-05-05

    The Developing Countries Vaccine Manufacturers' Network (DCVMN) held its fifteenth annual meeting from October 27-29, 2014, New Delhi, India. The DCVMN, together with the co-organizing institution Panacea Biotec, welcomed over 240 delegates representing high-profile governmental and nongovernmental global health organizations from 36 countries. Over the three-day meeting, attendees exchanged information about their efforts to achieve their shared goal of preventing death and disability from known and emerging infectious diseases. Special praise was extended to all stakeholders involved in the success of polio eradication in South East Asia and highlighted challenges in vaccine supply for measles-rubella immunization over the coming decades. Innovative vaccines and vaccine delivery technologies indicated creative solutions for achieving global immunization goals. Discussions were focused on three major themes including regulatory challenges for developing countries that may be overcome with better communication; global collaborations and partnerships for leveraging investments and enable uninterrupted supply of affordable and suitable vaccines; and leading innovation in vaccines difficult to develop, such as dengue, Chikungunya, typhoid-conjugated and EV71, and needle-free technologies that may speed up vaccine delivery. Moving further into the Decade of Vaccines, participants renewed their commitment to shared responsibility toward a world free of vaccine-preventable diseases. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  14. Magnetically responsive enzyme powders

    International Nuclear Information System (INIS)

    Pospiskova, Kristyna; Safarik, Ivo

    2015-01-01

    Powdered enzymes were transformed into their insoluble magnetic derivatives retaining their catalytic activity. Enzyme powders (e.g., trypsin and lipase) were suspended in various liquid media not allowing their solubilization (e.g., saturated ammonium sulfate and highly concentrated polyethylene glycol solutions, ethanol, methanol, 2-propanol) and subsequently cross-linked with glutaraldehyde. Magnetic modification was successfully performed at low temperature in a freezer (−20 °C) using magnetic iron oxides nano- and microparticles prepared by microwave-assisted synthesis from ferrous sulfate. Magnetized cross-linked enzyme powders were stable at least for two months in water suspension without leakage of fixed magnetic particles. Operational stability of magnetically responsive enzymes during eight repeated reaction cycles was generally without loss of enzyme activity. Separation of magnetically modified cross-linked powdered enzymes from reaction mixtures was significantly simplified due to their magnetic properties. - Highlights: • Cross-linked enzyme powders were prepared in various liquid media. • Insoluble enzymes were magnetized using iron oxides particles. • Magnetic iron oxides particles were prepared by microwave-assisted synthesis. • Magnetic modification was performed under low (freezing) temperature. • Cross-linked powdered trypsin and lipase can be used repeatedly for reaction

  15. Rapid response manufacturing (RRM)

    Energy Technology Data Exchange (ETDEWEB)

    Cain, W.D. [Lockheed Martin Energy Systems, Inc., Oak Ridge, TN (United States); Waddell, W.L. [National Centers for Manufacturing Sciences, Ann Arbor, MI (United States)

    1997-02-18

    US industry is fighting to maintain its competitive edge in the global market place. Today markets fluctuate rapidly. Companies, to survive, have to be able to respond with quick-to-market, improved, high quality, cost efficient products. The way products are developed and brought to market can be improved and made more efficient through the proper incorporation of emerging technologies. The RRM project was established to leverage the expertise and resources of US private industries and federal agencies to develop, integrate, and deploy new technologies that meet critical needs for effective product realization. The RRM program addressed a needed change in the US Manufacturing infrastructure that will ensure US competitiveness in world market typified by mass customization. This project provided the effort needed to define, develop and establish a customizable infrastructure for rapid response product development design and manufacturing. A major project achievement was the development of a broad-based framework for automating and integrating the product and process design and manufacturing activities involved with machined parts. This was accomplished by coordinating and extending the application of feature-based product modeling, knowledge-based systems, integrated data management, and direct manufacturing technologies in a cooperative integrated computing environment. Key technological advancements include a product model that integrates product and process data in a consistent, minimally redundant manner, an advanced computer-aided engineering environment, knowledge-based software aids for design and process planning, and new production technologies to make products directly from design application software.

  16. Joined and Responsible Parenting

    Directory of Open Access Journals (Sweden)

    Selmani-Bakiu Arta

    2017-06-01

    Full Text Available In the contemporary family law, parents are obliged to arrange the joined implementation of the parenting rights either by their own will or through the help of their lawyers and/or mediators. This institute of mutual agreement is known as joined custody or joined implementation of the parenting right after the divorce of the marriage. This institute makes it possible for parents who live separately to arrange their custody rights in the most convenient way for the child. With a joined custody agreement, the parents accept the obligation to implement all the rights and duties that constitute the parenting right even in case of their separation. Through not dividing their rights from their obligations and with the aim of being closer to the needs of the child, the institute of joined custody helps avoid the feelings of hostility and disagreement in regard to the judicial decision which gives permanent custody to one of the parents. This institute is incorporated in the family law of many countries (Sweden, Norway, Finland, Denmark, UK, France, Italy, Germany, Belgium, Switzerland, Hungary, Czech Republic, USA and Australia. This article aims to emphasize the need to introduce in the family law of RM an explicit provision for joined and responsible custody after the divorce in order to achieve the best interest of the child. There is a joined initiative of parents who live separately from their children who request the amendment of the Family Law of RM in this direction.

  17. Response to Glenn

    Directory of Open Access Journals (Sweden)

    Stephen Arons

    1998-01-01

    Full Text Available Arons responds to what he considers to be Glenn's misrepresentations of the tone and content of Short Route To Chaos. He writes that Glenn "appears to be attempting to construct the book's message into just one more salvo fired in the endless school wars. It is anything but....Reading Glenn's review, one is left with the impression that the book is a Christian-bashing, left-leaning, work of communitarian fuzziness in which a legal scholar unaccountably refuses to confine himself to ... technical explication of existing constitutional doctrine." In his response, Arons affirmatively sets out some of the book's main themes of political /cultural conflict over standardized schooling, corrects some of what he sees as Glenn's misunderstandings, and notes that the book itself invites readers to eschew partisanship and recognize that there are deep structural problems in American public education. In closing, Arons uses an example of Glenn's partisan misunderstanding that leads Arons to recommend to the reader that it would be better to read Short Route to Chaos for oneself.

  18. Technical risk - individual responsibility

    International Nuclear Information System (INIS)

    Herzog, R.

    1984-01-01

    The author, vice-president of the Federal Constitutional Court, delivered this opening address at the international symposium on nuclear liability held in Munich in September 1984 by OECD/NEA and IAEA. He starts by asking: Where does danger begin, where does risk end. It is the true and original task of the state to keep damage away from its citizens: this entails the obligation for additional garantees - not withstanding an almost greatest possible degree of safety - to at least helpfully compensate damage incurred, should such damage arise. In case of really severe accidents the essential thing is not the operator's liability but the entry of the state into that obligation, and this fact remains unchanged even if the maximum limits of liability were raised or in case of their removal. Therefore it is not necessary to be cautious about the question of unlimited liability, i.e. the unlimited entry of the state into such obligations, especially as all those responsible are convinced that there is practically no risk of that contingency occurring. (HSCH) [de

  19. Consumer Responses to Corporate Social Responsibility (CSR) in China

    OpenAIRE

    Lili, Chang; Jiaqi, Cheng

    2017-01-01

    With the development of multinational companies (MNCs), corporate social responsibility (CSR) has become a very important component of corporate activities. However, the commitment to CSR in China has been very low. Chinese consumers are becoming less willing to accept different treatment from MNCs, but there has been a little study of CSR problems in the Chinese market or the response of Chinese consumer. This study provides preliminary evidence that consumer response about the CSR behavior ...

  20. Detection and transfer of the glutamate decarboxylase gene in Streptococcus thermophilus

    Science.gov (United States)

    GABA (gamma-aminobutyric acid) is generated from glutamate by the action of glutamic acid decarboxylase (GAD) and characterized by hypotensive, diuretic and tranquilizing effects in humans and animals. The production of GABA by lactic acid starter bacteria would enhance the functionality of fermen...

  1. Gene expression of GABA and glutamate pathway markers in the prefrontal cortex of non-suicidal elderly depressed patients

    NARCIS (Netherlands)

    Zhao, J.; Bao, A.-M.; Qi, X.-R.; Kamphuis, W.; Luchetti, S.; Lou, J.-S.; Swaab, D. F.

    2012-01-01

    The prefrontal cortex (PFC) is presumed to be involved in the pathogenesis of depression. We determined the gene expression of 32 markers of the pathways of the two main neurotransmitters of the PFC, gamma-aminobutyric acid (GABA) and l-glutamic acid (glutamate), by real-time quantitative PCR in

  2. General anesthesia as a possible GABAergic modulator affects visual processing in children

    NARCIS (Netherlands)

    van den Boomen, C.; de Graaff, J. C.; de Jong, T. P. V. M.; Kalkman, C. J.; Kemner, C.

    2013-01-01

    Gamma-Aminobutyric Acid (GABA) inhibitory interneurons play an important role in visual processing, as is revealed by studies administering drugs in human and monkey adults. Investigating this process in children requires different methodologies, due to ethical considerations. The current study

  3. The Effects of Dopamine and Estrogen upon Cortical Parvalbumin Expression

    Science.gov (United States)

    2001-10-01

    on NMDA and AMPS receptors in rat brain. J Neuroendocrinol 12:455- 462 Cyr M, Landry M, Di Paolo T (2000b) Modulation by estrogen-receptor directed...gamma]-aminobutyric acid- accumulating intrinsic neuronal systems in monkey cerebral cortex. J Neurosci 5:3246-3260. Ferrer I, Casas R, Rivera R (1993

  4. Synthesis and accumulation of free amino acids during somatic and ...

    African Journals Online (AJOL)

    In ZE, glutamine and asparagine appeared to be fundamental to the process of induction of zygotic embryos. On the other hand, the induction of somatic embryos that appeared require glutamine, gamma-aminobutyric acid (GABA) and glutamic acid. The results suggest the involvement of amino acids in the ontogenesis of ...

  5. GABA receptors and benzodiazepine binding sites modulate hippocampal acetylcholine release in vivo

    NARCIS (Netherlands)

    Moor, E; de Boer, P; Westerink, B.H.C.

    1998-01-01

    In the present study, the regulation of acetylcholine release from the ventral hippocampus by gamma-aminobutyric acid (GABA) was investigated in vivo. GABA receptor agonists and antagonists were administered locally in the medial septum and the adjacent vertical limb of the diagonal band of Broca,

  6. Succinic semialdehyde dehydrogenase deficiency: Decrease in 4-OH-butyric acid levels with low doses of vigabatrin

    NARCIS (Netherlands)

    Escalera, G.I.; Ferrer, I.; Marina, L.C.; Sala, P.R.; Salomons, G.S.; Jakobs, C.; Perez-Cerda, C.

    2010-01-01

    Succinic semialdehyde dehydrogenase deficiency (gamma-hydroxybutyric aciduria) is a rare neurometabolic disease caused by a deficiency in gamma-aminobutyric degradation, resulting in an increase in gamma-hydroxybutyric acid in biological fluids. The clinical spectrum is heterogeneous, including a

  7. Involvement of medial septal glutamate and GABA(A) receptors in behaviour-induced acetylcholine release in the hippocampus : A dual probe microdialysis study

    NARCIS (Netherlands)

    Moor, E; Schirm, E; Jacso, J; Westerink, BHC

    1998-01-01

    In the present study, the role of medial septal receptors in behaviour-induced increase in acetylcholine (ACh) release in hippocampus was investigated using dual-probe microdialysis in combination with a simple behavioural procedure, gamma-Aminobutyric acid (GABA) and glutamate receptor agonists and

  8. Synthesis and GABAA receptor activity of A-homo analogues of neuroactive steroids

    Czech Academy of Sciences Publication Activity Database

    Dansey, M. V.; Di Chenna, P.; Valeiro, A. S.; Krištofíková, Z.; Chodounská, Hana; Kasal, Alexander; Burton, G.

    2010-01-01

    Roč. 45, č. 7 (2010), s. 3063-3069 ISSN 0223-5234 R&D Projects: GA ČR(CZ) GA203/08/1498 Institutional research plan: CEZ:AV0Z40550506 Keywords : A-homopregnane * neurosteroid * gamma-aminobutyric acid * GABAA receptor Subject RIV: CC - Organic Chemistry Impact factor: 3.193, year: 2010

  9. Brain GABA levels across psychiatric disorders : A systematic literature review and meta-analysis of 1H-MRS studies

    NARCIS (Netherlands)

    Schür, Remmelt R.; Draisma, Luc W R; Wijnen, Jannie P.; Boks, Marco P.; Koevoets, Martijn G J C; Joëls, Marian; Klomp, Dennis W.; Kahn, René S.; Vinkers, Christiaan H.

    2016-01-01

    The inhibitory gamma-aminobutyric acid (GABA) system is involved in the etiology of most psychiatric disorders, including schizophrenia, autism spectrum disorder (ASD) and major depressive disorder (MDD). It is therefore not surprising that proton magnetic resonance spectroscopy (1H-MRS) is

  10. Novel high-affinity and selective biaromatic 4-substituted ¿-hydroxybutyric acid (GHB) analogues as GHB ligands

    DEFF Research Database (Denmark)

    Høg, Signe; Wellendorph, Petrine; Nielsen, Birgitte

    2008-01-01

    Gamma-hydroxybutyrate (GHB) is a metabolite of gamma-aminobutyric acid (GABA) and has been proposed to function as a neurotransmitter or neuromodulator. GHB is used in the treatment of narcolepsy and is a drug of abuse. GHB binds to both GABA(B) receptors and specific high-affinity GHB sites...

  11. Brief Report: Pilot Single-Blind Placebo Lead-in Study of Acamprosate in Youth with Autistic Disorder

    Science.gov (United States)

    Erickson, Craig A.; Wink, Logan K.; Early, Maureen C.; Stiegelmeyer, Elizabeth; Mathieu-Frasier, Lauren; Patrick, Vanessa; McDougle, Christopher J.

    2014-01-01

    Rationale: An excitatory/inhibitory (E:I) imbalance marked by enhanced glutamate and deficient gamma-aminobutyric acid (GABA) neurotransmission may contribute to the pathophysiology of autism spectrum disorders (ASD). Objectives: We report on the first single-blind placebo lead-in trial of acamprosate, a drug with putative mechanisms restoring E:I…

  12. Conditional gene deletion reveals functional redundancy of GABAB receptors in peripheral nociceptors in vivo

    NARCIS (Netherlands)

    Gangadharan, Vijayan; Agarwal, Nitin; Brugger, Stefan; Tegeder, Imgard; Bettler, Bernhard; Kuner, Rohini; Kurejova, Martina

    2009-01-01

    BACKGROUND: gamma-aminobutyric acid (GABA) is an important inhibitory neurotransmitter which mainly mediates its effects on neurons via ionotropic (GABA(A)) and metabotropic (GABA(B)) receptors. GABA(B) receptors are widely expressed in the central and the peripheral nervous system. Although there

  13. Acute desensitization of presynaptic GABA(B)-mediated inhibition and induction of epileptiform discharges in the neonatal rat hippocampus

    NARCIS (Netherlands)

    Tosetti, P; Bakels, R; Colin-Le Brun, [No Value; Ferrand, N; Gaiarsa, JL; Caillard, O

    The consequences of sustained activation of GABA(B) receptors on GABA(B)-mediated inhibition and network activity were investigated in the neonatal rat hippocampus using whole-cell and extracellular field recordings. GABA(B)-mediated presynaptic control of gamma-aminobutyric acid (GABA) release

  14. GABAERGIC MODULATION OF STRIATAL CHOLINERGIC INTERNEURONS - AN IN-VIVO MICRODIALYSIS STUDY

    NARCIS (Netherlands)

    DEBOER, P; WESTERINK, BHC

    Striatal cholinergic interneurons have been shown to receive input from striatal gamma-aminobutyric acid (GABA)-containing cell elements. GABA is known to act on two different types of receptors, the GABA(A) and the GABA(B) receptor. Using in vivo microdialysis, we have studied the effect of

  15. GABA Concentrations in the Anterior Cingulate Cortex Are Associated with Fear Network Function and Fear Recovery in Humans

    NARCIS (Netherlands)

    Levar, Nina; van Leeuwen, Judith M. C.; Puts, Nicolaas A. J.; Denys, Damiaan; van Wingen, Guido A.

    2017-01-01

    Relapse of fear after successful treatment is a common phenomenon in patients with anxiety disorders. Animal research suggests that the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) plays a key role in the maintenance of extinguished fear. Here, we combined magnetic resonance

  16. CHARACTERIZATION OF EXTRACELLULAR GABA IN THE SUBSTANTIA-NIGRA-RETICULATA BY MEANS OF BRAIN MICRODIALYSIS

    NARCIS (Netherlands)

    TIMMERMAN, W; ZWAVELING, J; WESTERINK, BHC

    Brain microdialysis was used to characterize extracellular gamma-aminobutyric acid (GABA) in the substantia nigra reticulata (SNR) of freely moving rats. The extracellular GABA in the SNR was characterized using acutely implanted probes (4-8 h after surgery; day 1) and chronically implanted probes

  17. Divergent influences of anterior cingulate cortex GABA concentrations on the emotion circuitry

    NARCIS (Netherlands)

    Levar, Nina; van Leeuwen, Judith M. C.; Denys, Damiaan; van Wingen, Guido A.

    2017-01-01

    Neuroimaging research has revealed that emotion processing recruits a widespread neural network including the dorsal anterior cingulate cortex (dACC), hippocampus, and amygdala. Recent studies have started to investigate the role of the primary inhibitory neurotransmitter gamma-aminobutyric acid

  18. HPLC conditions are critical for the detection of GABA by microdialysis

    NARCIS (Netherlands)

    Rea, Kieran; Cremers, T.I.F.H.; Westerink, B.H.C.

    In microdialysis studies, neither exocytotic release of gamma-aminobutyric acid (GABA), nor the presence of GABA type B (GABA(B)) autoreceptors, have been clearly established. It was investigated whether the chromatographic separation of GABA may have contributed to discrepancies in the literature.

  19. Genome Sequence of Lactococcus lactis subsp. lactis NCDO 2118, a GABA-Producing Strain

    DEFF Research Database (Denmark)

    Oliveira, Letícia C; Saraiva, Tessália D L; Soares, Siomar C

    2014-01-01

    Lactococcus lactis subsp. lactis NCDO 2118 is a nondairy lactic acid bacterium, a xylose fermenter, and a gamma-aminobutyric acid (GABA) producer isolated from frozen peas. Here, we report the complete genome sequence of L. lactis NCDO 2118, a strain with probiotic potential activity....

  20. NMDA receptor-dependent GABA(B) receptor internalization via CaMKII phosphorylation of serine 867 in GABA(B1)

    Czech Academy of Sciences Publication Activity Database

    Guetg, N.; Aziz, S. A.; Holbro, N.; Tureček, Rostislav; Rose, T.; Seddik, R.; Gassmann, M.; Moes, S.; Jenoe, P.; Oertner, T.G.; Casanova, E.; Bettler, B.

    2010-01-01

    Roč. 107, č. 31 (2010), s. 13924-13929 ISSN 0027-8424 Grant - others:EU(XE) LSHM-CT-2005-019055 Institutional research plan: CEZ:AV0Z50390512 Keywords : gamma-aminobutyric acid * spines * trafficking Subject RIV: FH - Neurology Impact factor: 9.771, year: 2010

  1. Anticonvulsant and sedative effect of Fufang Changniu pills and ...

    African Journals Online (AJOL)

    Finally, PTZ-induced chronic seizures were established, and expressions of gamma-aminobutyric acid A receptor (GABA-A) and glutamic acid decarboxylase 65 (GAD65) in the brains of the mice were assayed by western blot in order to explore the probable mechanisms of action of the drug. Results: Gallic acid, liquiritin, ...

  2. GABA, a natural immunomodulator of T lymphocytes

    DEFF Research Database (Denmark)

    Bjurstöm, Helen; Wang, Junyang; Ericsson, Ida

    2008-01-01

    gamma-aminobutyric acid (GABA) is the main neuroinhibitory transmitter in the brain. Here we show that GABA in the extracellular space may affect the fate of pathogenic T lymphocytes entering the brain. We examined in encephalitogenic T cells if they expressed functional GABA channels that could ......M and higher GABA concentrations decreased T cell proliferation. The results are consistent with GABA being immunomodulatory....

  3. Genetic and bibliographic information: Gabra4 [GenLibi

    Lifescience Database Archive (English)

    Full Text Available ses (C10) > Central Nervous System Diseases (C10.228) > Brain Diseases (C10.228.140...) > Epilepsy (C10.228.140.490) > Seizures (C10.228.140.490.631) Nervous System Diseases (C10) > Neurologic M...Gabra4 gamma-aminobutyric acid (GABA) A receptor, subunit alpha 4 mouse Seizures (MeSH) Nervous System Disea

  4. Differential compartmentalization and distinct functions of GABAB receptor variants

    DEFF Research Database (Denmark)

    Vigot, Réjan; Barbieri, Samuel; Bräuner-Osborne, Hans

    2006-01-01

    GABAB receptors are the G protein-coupled receptors for the main inhibitory neurotransmitter in the brain, gamma-aminobutyric acid (GABA). Molecular diversity in the GABAB system arises from the GABAB1a and GABAB1b subunit isoforms that solely differ in their ectodomains by a pair of sushi repeat...

  5. Pushing the Margins of Responsibility

    DEFF Research Database (Denmark)

    Santoni de Sio, Filippo; Di Nucci, Ezio

    2018-01-01

    ’ marginal responsibility in three steps: we first deny that Parks acts involuntarily as traditionally claimed in the legal literature; we then propose to extend Shoemaker’s analysis of marginal responsibility based on quality of will so as to include two other dimensions: the moral status of the agent......David Shoemaker has claimed that a binary approach to moral responsibility leaves out something important, namely instances of marginal agency, cases where agents seem to be eligible for some responsibility responses but not others. In this paper we endorse and extend Shoemaker’s approach...... by presenting and discussing one more case of marginal agency not yet covered by Shoemaker or in the other literature on moral responsibility. Our case is that of Kenneth Parks, a Canadian man who drove a long way to his mother-in-law’s and killed her in a state of somnambulism. We support our claim about Parks...

  6. Improving tumour response

    International Nuclear Information System (INIS)

    Bentzen, S.

    2003-01-01

    Radiation oncology is in the middle of the most exciting developments in its 100-year history. Progress in treatment planning and delivery, in medical imaging and in basic cancer and normal tissue biology is likely to change the indication for radiotherapy as well as the way it is prescribed and delivered. Technological and conceptual advances, in particular the development of the multi-leaf collimator and the concept of inverse treatment planning, have led to the introduction of intensity modulated radiation therapy (IMRT) with its capability to plan and deliver non-uniform dose distributions in the clinic. This has forced us to re-think radiation oncology: refining the indication for radiotherapy, optimizing the prescription of dose distributions and considering how, based on clinical evidence, radiation can best be combined with other treatment modalities, surgery, cytotoxic chemotherapy and biologically targeted therapies. The attraction of radiation therapy as an element of multi-modality cancer therapy is that it induces DNA damage that can be modulated in space and time. Progress in basic cancer biology, genomics and proteomics, as well as biological imaging provides novel avenues for individualization of cancer therapy and for biological optimization of radiotherapy. In improving cancer care, it is the therapeutic ratio, rather than tumour control per se, that must be optimised. Interestingly, the two main avenues for improving the effectiveness of radiotherapy currently being actively pursued in the clinic generally aim at different sides of the therapeutic ratio: 3D conformal radiotherapy and IMRT predominantly aim to reduce normal-tissue side effects - and by doing this, open the way for dose escalation that may lead to increased tumour control rates - whereas combined radio-chemotherapy aims to improve tumour response - while keeping the fingers crossed that this will not increase normal-tissue complications to the same extent. In parallel with these

  7. Increasing paternal responsibility.

    Science.gov (United States)

    Cutright, P

    1985-01-01

    Increasing numbers of fathers of children born out of wedlock are not contributing to these children's economic support. In 1981, a tiny minority (14%) of the 1.7 million never-married mothers living with a child with an absent father had a child-support award, and of these, just 112,000 actually received some payment in 1981. The high rates of noncompliance, and the low level of legal efforts to enforce child support, are the result of attempts to collect payments through inefficient traditional methods, not the inability of fathers to pay, a Wisconsin study has shown. A basic problem with collecting child support under the present system is that it relies on fathers to control their expenditures and voluntarily to send the payment on a weekly, biweekly or monthly basis, year after year. As a Wisconsin study shows, full compliance with court-ordered payments dropped from 38% in the 1st year to below 20% by the 5th year among 163 ex-husbands tracked. A proposal by researchers at the University of Wisconsin's Institute for Research on Poverty calls for an "absent-parent tax." The Wisconsin Plan, as it is known, is simply a withholding tax based on the father's gross income and the number of his absent children. If his income falls below a certain level, payments will stop automatically, but will resume if and when it rises above the cutoff point. The Wisconsin plan removes all judicial discretion and lawyer's skill as factors in child-support awards, thus eliminating erratic awards. It also insures that support payments will be maintained during periods of conflict between the father and mother. However, before the Wisconsin Plan can effectively protect children both out of wedlock, a feature needs to be added that will establish paternity at birth. Imposing a real child-support obligation on fathers of children born outside of marriage will introduce a potentially powerful economic incentive for responsible male reproductive and parental behavior.

  8. Responsible nanotechnology development

    Energy Technology Data Exchange (ETDEWEB)

    Forloni, Gianluigi, E-mail: forloni@marionegri.it [Istituto di Ricerche Farmacologiche ' Mario Negri' , Department of Neuroscience (Italy)

    2012-08-15

    approach to the nanotoxicology. The establishment of an effective strategy cannot ignore the distinction between different nanoparticles on their use and the type of exposure to which we are subjected. Categorization is essential to orchestrate toxicological rules realistic and effective. The responsible development of nanotechnology means a common effort, by scientists, producers, stakeholders, and public institutions to develop appropriate programs to systematically approach the complex issue of the nanotoxicology.

  9. Responsible nanotechnology development

    International Nuclear Information System (INIS)

    Forloni, Gianluigi

    2012-01-01

    to the nanotoxicology. The establishment of an effective strategy cannot ignore the distinction between different nanoparticles on their use and the type of exposure to which we are subjected. Categorization is essential to orchestrate toxicological rules realistic and effective. The responsible development of nanotechnology means a common effort, by scientists, producers, stakeholders, and public institutions to develop appropriate programs to systematically approach the complex issue of the nanotoxicology.

  10. Responsible nanotechnology development

    Science.gov (United States)

    Forloni, Gianluigi

    2012-08-01

    the nanotoxicology. The establishment of an effective strategy cannot ignore the distinction between different nanoparticles on their use and the type of exposure to which we are subjected. Categorization is essential to orchestrate toxicological rules realistic and effective. The responsible development of nanotechnology means a common effort, by scientists, producers, stakeholders, and public institutions to develop appropriate programs to systematically approach the complex issue of the nanotoxicology.

  11. Psychobiology of the placebo response.

    Science.gov (United States)

    Klosterhalfen, Sibylle; Enck, Paul

    2006-04-30

    The nature and determinants of the placebo response are widely unknown and are discussed controversially. This review presents a unifying concept for the understanding of the placebo response in clinical trials and practice based on three components: "Regression to the mean", "Pavlovian conditioning", and "Signal detection theory", and discusses the respective literature in light of experimental and clinical findings from psychology, psychiatry, neurology, and gastroenterology, with specific emphasis on "brain imaging" of the placebo response.

  12. Property Rights, Restrictions and Responsibilities

    DEFF Research Database (Denmark)

    Enemark, Stig

    more to a social, ethical commitment or attitude to environmental sustainability and good husbandry. This paper provides an overall understanding of the concept of land administration systems for dealing with rights, restrictions and responsibilities in future spatially enabled government. Finally......Land Administration Systems are the basis for conceptualizing rights, restrictions and responsibilities related to people, policies and places. Property rights are normally concerned with ownership and tenure whereas restrictions usually control use and activities on land. Responsibilities relate...

  13. Network Culture, Performance & Corporate Responsibility

    OpenAIRE

    Silvio M. Brondoni

    2003-01-01

    The growth and sustainability of free market economies highlights the need to define rules more suited to the current condition of market globalisation and also encourages firms to adopt more transparent and accountable corporate responsibility (and corporate social responsibility, namely the relationship between the company, environment and social setting). From a managerial perspective, corporate responsibility is linked to ensure the lasting pursuit of the company mission, seeking increasi...

  14. Corporate Social Responsibility in Ukraine

    OpenAIRE

    Stepanenko, Ievgeniia

    2012-01-01

    In the article are considered essence of corporate social responsibility and terms necessary for realization of social activity management subjects. Hikes over are brought to realization of corporate social responsibility, meaningfulness of large and middle business is certain in becoming of social responsibility of enterprises. It is set that exactly midsize business must come forward as a main motor of economic development of Ukraine. Becoming features and modern state of corporate social r...

  15. Rights and responsibilities in Darfur

    Directory of Open Access Journals (Sweden)

    Katherine Reyes

    2009-09-01

    Full Text Available A combined UN-military-police-humanitarian initiative hasbeen promoting civic rights and responsibilities among IDPsin order to increase security throughout Kalma camp and itssurroundings.

  16. Leadership Development: A Supervisory Responsibility

    National Research Council Canada - National Science Library

    French, David

    2000-01-01

    .... This is a recurring theme found throughout leadership literature and speeches. The US Air Force clearly establishes subordinate development as a supervisory responsibility in top-level doctrine...

  17. Personal Responsibility and Lifestyle Diseases

    DEFF Research Database (Denmark)

    Andersen, Martin Marchman; Nielsen, Morten Ebbe Juul

    2016-01-01

    What does it take for an individual to be personally responsible for behaviors that lead to increased risk of disease? We examine three approaches to responsibility that cover the most important aspects of the discussion of responsibility and spell out what it takes, according to each of them......, to be responsible for behaviors leading to increased risk of disease. We show that only what we call the causal approach can adequately accommodate widely shared intuitions to the effect that certain causal influences—such as genetic make-up or certain social circumstances—diminish, or undermine personal...

  18. Demand response in energy markets

    International Nuclear Information System (INIS)

    Skytte, K.; Birk Mortensen, J.

    2004-11-01

    Improving the ability of energy demand to respond to wholesale prices during critical periods of the spot market can reduce the total costs of reliably meeting demand, and the level and volatility of the prices. This fact has lead to a growing interest in the short-run demand response. There has especially been a growing interest in the electricity market where peak-load periods with high spot prices and occasional local blackouts have recently been seen. Market concentration at the supply side can result in even higher peak-load prices. Demand response by shifting demand from peak to base-load periods can counteract the market power in the peak-load. However, demand response has so far been modest since the current short-term price elasticity seems to be small. This is also the case for related markets, for example, green certificates where the demand is determined as a percentage of the power demand, or for heat and natural gas markets. This raises a number of interesting research issues: 1) Demand response in different energy markets, 2) Estimation of price elasticity and flexibility, 3) Stimulation of demand response, 4) Regulation, policy and modelling aspects, 5) Demand response and market power at the supply side, 6) Energy security of supply, 7) Demand response in forward, spot, ancillary service, balance and capacity markets, 8) Demand response in deviated markets, e.g., emission, futures, and green certificate markets, 9) Value of increased demand response, 10) Flexible households. (BA)

  19. Item Response Data Analysis Using Stata Item Response Theory Package

    Science.gov (United States)

    Yang, Ji Seung; Zheng, Xiaying

    2018-01-01

    The purpose of this article is to introduce and review the capability and performance of the Stata item response theory (IRT) package that is available from Stata v.14, 2015. Using a simulated data set and a publicly available item response data set extracted from Programme of International Student Assessment, we review the IRT package from…

  20. PENGARUH PENGUNGKAPAN CORPORATE SOCIAL RESPONSIBILITY TERHADAP EARNING RESPONSE COEFFICIENT

    Directory of Open Access Journals (Sweden)

    MI Mitha Dwi Restuti

    2012-03-01

    Full Text Available Tujuan penelitian ini adalah untuk mengetahui pengaruh negatif pengungkapan Corporate Sosial Responsibility (CSR disclosure terhadap Earning Response Coefficient (ERC. Alat analisis yang digunakan dalam penelitian ini menggunakan metode analisis regresi berganda.Sampel yang digunakan adalah sebanyak 150 perusahaan yang terdaftar pada Bursa Efek Indonesia pada tahun 2010. Berdasarkan hasil penelitian ditemukan bahwa pengungkapan Corporate Social Responsibility tidak berpengaruh terhadap Earning Response Coefficient (ERC. Hal ini dapat dikatakan bahwa investor belum memperhatikan informasi-informasi sosial yang diungkapkan dalam laporan tahunan perusahaan sebagai informasi yang dapat mempengaruhi investor dalam melakukan keputusan investasi. Investor masih mengganggap informasi laba lebih bermanfaat dalam menilai perusahaan dan dianggap lebih mampu memberikan informasi untuk mendapatkan return saham yang diharapkan oleh investor dibandingkan dengan informasi sosial yang diungkapkan oleh perusahaan.The purpose of this study is to determine the negative effect of Corporate Social Responsibility disclosure (CSR disclosure of Earnings Response Coefficient (ERC. Multiple regressions were used to analyze the data. The samples were 150 companies listed on the Indonesia Stock Exchange in 2010. Based on the research, the result was the disclosures of Corporate Social Responsibility did not influence Earning Response Coefficient (ECR. It can be said that investors did not pay attention to social information that was disclosed in the company’s annual report as information that could affect investors in making investment decisions. Investor did not consider sosial information; they only consider profit information to assess the company value and their investment return

  1. Response Strategies and Response Styles in Cross-Cultural Surveys

    NARCIS (Netherlands)

    Morren, M.H.; Gelissen, J.P.T.M.; Vermunt, J.K.

    2012-01-01

    This article addresses the following research questions: Do respondents participating in cross-cultural surveys differ in their response style when responding to attitude statements? If so, are characteristics of the response process associated with their ethnicity and generation of immigration? To

  2. Strychnine blocks transient but not sustained inhibition in mudpuppy retinal ganglion cells.

    Science.gov (United States)

    Belgum, J H; Dvorak, D R; McReynolds, J S

    1984-01-01

    Transient and sustained inhibitory synaptic inputs to on-centre, off-centre, and on-off ganglion cells in the mudpuppy retina were studied using intracellular recording in the superfused eye-cup preparation. When chemical transmission was blocked with 4 mM-Co2+, application of either glycine or gamma-aminobutyric acid (GABA) caused a hyperpolarization and conductance increase in all ganglion cells. For both amino acids, the responses were dose dependent in the range 0.05-10 mM, with a half-maximal response at about 0.7 mM. Glycine and GABA sensitivities were very similar in all three types of ganglion cells. The response to applied glycine was selectively antagonized by 10(-5) M-strychnine and the response to applied GABA was selectively antagonized by 10(-5) M-picrotoxin. In all ganglion cells, 10(-5) M-strychnine eliminated the transient inhibitory events which occur at the onset and termination of a light stimulus. The block of transient inhibition was associated with a relative depolarization of membrane potential and decrease in conductance at these times. Strychnine had no effect on membrane potential or conductance in darkness or during sustained inhibitory responses to light. Picrotoxin (10(-5) M) did not block transient inhibitory events in any ganglion cells, but did affect other components of their responses. The results suggest that in all three classes of ganglion cells transient inhibition, but not sustained inhibition, may be mediated by glycine or a closely related substance. PMID:6481635

  3. Cardiovascular Responses to Electromagnetic Radiation

    African Journals Online (AJOL)

    Dr Olaleye Samuel

    It has been reported that significant responses take place in brain glucose metabolism (Volkow et al 2011). Iron containing mitochondrial respiratory enzymes can also be directly involved in this response. Also blood-brain barrier problems exist at least in experimental animals (Nittby et al 2009). An increase of brain tumors ...

  4. Responsiveness of Clinical Outcome Measures

    DEFF Research Database (Denmark)

    Lauridsen, Henrik Hein

    the MCID (MCIDpost). Results The responsiveness in subgroups study. The ODI measurement error ranged between -11.5 and +13 points. Responsiveness was comparable to the external measures. A floor effect was seen in the PrS patients. The MCID was nine points in PrS and LBP only patients and eight points...

  5. [On-scene medical response].

    Science.gov (United States)

    Dinot, Emmanuel

    2017-04-01

    In cases of exceptional medical emergencies, the setting up and organisation of a response to the increased need for medical aid are complex. Command of the operations and responsibilities are assured by specific people depending on the seriousness of the situation. Each role is identified. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  6. Systemic inflammatory responses in asthma

    NARCIS (Netherlands)

    Hove, W. ten

    2007-01-01

    In asthma, inflammatory cells undergo a process referred to as priming. During priming responses, cells are not directly activated by inflammatory stimuli, but acquire increased responsiveness towards heterologous stimuli. The focus of the studies presented in the thesis of Willem ten Hove was

  7. Strategic War Game - Arctic Response

    Science.gov (United States)

    2010-11-01

    Arctic Game Theory Strategic Analysis War Game ... Strategic War Game – Arctic Response A. P. Billyard I. A. Collin H. A. Hrychuk Canadian Forces Aerospace Warfare Center Operational...Operational Research Strategic War Game – Arctic Response A. P. Billyard I. A. Collin H. A. Hrychuk Canadian Forces Aerospace

  8. Psychophysiological responses to Salsa dance.

    Directory of Open Access Journals (Sweden)

    Laura Guidetti

    Full Text Available Speculation exists whether dance provides physiological stimuli adequate to promote health and fitness benefits. Unfortunately, research to date has not addressed the affective and exertional responses to dance. These responses are of interest as positive affective and exertional responses experienced during physical activity may play an important role in predicting adherence. The present study aims to examine the psychophysiological responses of different Salsa dance styles. Ten pairs of dancers performed two different structured lessons of Salsa dance, including Typical Salsa and Rueda de Casino lessons, and a non-structured Salsa dance at a night club. Physiological responses (i.e., percent of heart rate reserve; %HRR were continuously assessed and perceived exertion and affective valence were rated every 15 min throughout the trials. %HRR responses differed between the Salsa dance styles (%HRR from 41.3 to 51.9%, and participants were dancing at intensities near their ventilatory threshold. Specifically, Typical Salsa lesson elicited lower %HRR responses than Rueda de Casino lesson (p 0.05. Surprisingly, exertional (from 8 to 11 and affective (from +3 to +5 responses were unaffected by Salsa dance styles (p > 0.05. These data support that different Salsa dance styles provide physiological stimuli adequate to promote health and fitness benefits, and perhaps more importantly, produce pleasurable experiences, which in turn might lead to an increase in adherence to Salsa dancing which likely provides exercise-like health benefits.

  9. Gender and international crisis response

    DEFF Research Database (Denmark)

    Eklund, Lisa; Tellier, Siri

    2012-01-01

    For more than a decade the humanitarian community has been mandated to mainstream gender in its response to crises. One element of this mandate is a repeated call for sex-disaggregated data to help guide the response. This study examines available analyses, assessments and academic literature...

  10. Psychophysiological responses to Salsa dance.

    Science.gov (United States)

    Guidetti, Laura; Buzzachera, Cosme Franklim; Emerenziani, Gian Pietro; Meucci, Marco; Saavedra, Francisco; Gallotta, Maria Chiara; Baldari, Carlo

    2015-01-01

    Speculation exists whether dance provides physiological stimuli adequate to promote health and fitness benefits. Unfortunately, research to date has not addressed the affective and exertional responses to dance. These responses are of interest as positive affective and exertional responses experienced during physical activity may play an important role in predicting adherence. The present study aims to examine the psychophysiological responses of different Salsa dance styles. Ten pairs of dancers performed two different structured lessons of Salsa dance, including Typical Salsa and Rueda de Casino lessons, and a non-structured Salsa dance at a night club. Physiological responses (i.e., percent of heart rate reserve; %HRR) were continuously assessed and perceived exertion and affective valence were rated every 15 min throughout the trials. %HRR responses differed between the Salsa dance styles (%HRR from 41.3 to 51.9%), and participants were dancing at intensities near their ventilatory threshold. Specifically, Typical Salsa lesson elicited lower %HRR responses than Rueda de Casino lesson (p dance at a night club condition (p > 0.05). Surprisingly, exertional (from 8 to 11) and affective (from +3 to +5) responses were unaffected by Salsa dance styles (p > 0.05). These data support that different Salsa dance styles provide physiological stimuli adequate to promote health and fitness benefits, and perhaps more importantly, produce pleasurable experiences, which in turn might lead to an increase in adherence to Salsa dancing which likely provides exercise-like health benefits.

  11. What is personal health responsibility?

    Science.gov (United States)

    Horton, Shalonda Estelle-Brazzell

    2014-01-01

    This case study examined the meaning of personal health responsibility from the perspective of the individual. A single Black female, 20 years of age, was interviewed for the study. Content analysis was used for data evaluation. The meaning of personal health responsibility grouped into four categories: listing of tasks, obligating to tasks, following through with tasks, and maintaining resources. Tasks are behaviors performed to care for oneself. Obligating to tasks is the attitude towards carrying out behaviors. Following through is the actual completion of a task. Maintaining resources is the support needed to care for oneself. The individual's definition of personal health responsibility should be considered when making healthcare decisions and designing treatment plans. Future research should examine the meaning of personal health responsibility among diverse populations and explore factors that serve as facilitators and barriers to personal health responsibility.

  12. Mapping 'Social Responsibility' in Science

    DEFF Research Database (Denmark)

    Glerup, Cecilie; Horst, Maja

    2014-01-01

    aims to exclude the social from the scientific production in order to make it objective and thereby responsible; the Reflexivity rationality, which sees it as science's responsibility to let itself be guided by problems in society in choice of research focus and methods; the Contribution rationality......, which insists that responsible science should live up to public demands for innovation and democracy; and the Integration rationality, which advocates that science should be co-constructed with societal actors in order to be socially responsible. While each rationality is distinct, the article argues......This article employs the Foucauldian notion of ‘political rationality’ to map discussions and ideals about the responsibility of science toward society. By constructing and analyzing an archive of 263 journal papers, four political rationalities were identified: the Demarcation rationality, which...

  13. Emotional response towards food packaging

    DEFF Research Database (Denmark)

    Liao, Lewis Xinwei; Corsi, Armando M.; Chrysochou, Polymeros

    2015-01-01

    In this paper we investigate consumers’ emotional responses to food packaging. More specifically, we use self-report and physiological measures to jointly assess emotional responses to three typical food packaging elements: colours (lowwavelength vs. high-wavelength), images (positive vs. negative...... response that can only be measured by self-report measures. We propose that a joint application of selfreport and physiological measures can lead to richer information and wider interpretation of consumer emotional responses to food packaging elements than using either measure alone.......) and typefaces (simple vs. ornate). A sample of 120 participants was exposed to mock package design concepts of chocolate blocks. The results suggest that images generate an emotional response that can be measured by both self-report and physiological measures, whereas colours and typefaces generate emotional...

  14. 7-Chloro-3-methyl-3,4-dihydro-2H-1,2,4-benzothiadiazine S,S-dioxide (IDRA 21), a congener of aniracetam, potently abates pharmacologically induced cognitive impairments in patas monkeys.

    Science.gov (United States)

    Thompson, D M; Guidotti, A; DiBella, M; Costa, E

    1995-08-15

    We report here on the ability of IDRA 21 and aniracetam, two negative allosteric modulators of glutamate-induced DL-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor desensitization, to attenuate alprazolam-induced learning deficit in patas monkeys working in a complex behavioral task. In one component of a multiple schedule (repeated acquisition or "learning"), patas monkeys acquired a different four-response chain each session by responding sequentially on three keys in the presence of four discriminative stimuli (geometric forms or numerals). In the other component (performance) the four-response chain was the same each session. The response chain in each component was maintained by food presentation under a fixed-ratio schedule. When alprazolam (0.1 or 0.32 mg/kg p.o.) was administered alone, this full allosteric modulator of gamma-aminobutyric acid type A (GABAA) receptors produced large decreases in the response rate and accuracy in the learning component of the task. IDRA 21 (3 or 5.6 mg/kg p.o.) and aniracetam (30 mg/kg p.o.) administered 60 min before alprazolam, having no effect when given alone, antagonized the large disruptive effects of alprazolam on learning. From dose-response studies, it can be estimated that IDRA 21 is approximately 10-fold more potent than aniracetam in antagonizing alprazolam-induced learning deficit. We conclude that IDRA 21, a chemically unrelated pharmacological congener of aniracetam, improves learning deficit induced in patas monkeys by the increase of GABAergic tone elicited by alprazolam. Very likely IDRA 21 exerts its behavioral effects by antagonizing AMPA receptor desensitization.

  15. National Response Team (NRT) Member Roles and Responsibilities

    Science.gov (United States)

    EPA personnel chair the NRT and cochair all Regional Response Teams (RRTs). They provide On-Scene Coordinators (OSCs), scientific support coordinators for inland spills, and Remedial Project Managers for hazardous waste remedial actions under Superfund.

  16. Eliminating mirror responses by instructions.

    Science.gov (United States)

    Bardi, Lara; Bundt, Carsten; Notebaert, Wim; Brass, Marcel

    2015-09-01

    The observation of an action leads to the activation of the corresponding motor plan in the observer. This phenomenon of motor resonance has an important role in social interaction, promoting imitation, learning and action understanding. However, mirror responses not always have a positive impact on our behavior. An automatic tendency to imitate others can introduce interference in action execution and non-imitative or opposite responses have an advantage in some contexts. Previous studies suggest that mirror tendencies can be suppressed after extensive practice or in complementary joint action situations revealing that mirror responses are more flexible than previously thought. The aim of the present study was to gain insight into the mechanisms that allow response flexibility of motor mirroring. Here we show that the mere instruction of a counter-imitative mapping changes mirror responses as indexed by motor evoked potentials (MEPs) enhancement induced by transcranial magnetic stimulation (TMS). Importantly, mirror activation was measured while participants were passively watching finger movements, without having the opportunity to execute the task. This result suggests that the implementation of task instructions activates stimulus-response association that can overwrite the mirror representations. Our outcome reveals one of the crucial mechanisms that might allow flexible adjustments of mirror responses in different contexts. The implications of this outcome are discussed. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Ventilatory Responses to Exercise While Eliciting the Relaxation Response,

    Science.gov (United States)

    1982-04-16

    been observed with the elicitation of the relaxation response at rest differ from those that occur during sleep or hypnosis (14). The relaxation response...alterations which were observed in our experimental group during the intervention period were not similar to those found with combined hypnosis and...the work of respiratory effort was observed in this group. This was implied by the finding of a relatively stable V02 in the face of a decreased VE and

  18. Responses of elderly spouse caregivers.

    Science.gov (United States)

    Given, B; Stommel, M; Collins, C; King, S; Given, C W

    1990-04-01

    In this paper three categories of variables were identified to predict spouses' reactions to caregiving roles: patient characteristics, the caregiving environment, and characteristics of the caregiver. Measures of these variables were administered to 159 spouse caregivers. Four domains of caregivers' responses were identified: negative emotional reactions, feelings of responsibility for the patient, feelings of abandonment by family, and impact of caregiving on daily schedules. These domains were influenced most by patient negative behaviors, physical health, and age, and by caregiver age, employment, and emotional status. Amount of assistance, affective support, and hours of care also were predictive of spouse responses.

  19. Corporate Responsibility and Sustainable Development

    OpenAIRE

    Paolo Ricotti

    2003-01-01

    Corporate responsibility marks a historical turnaround in corporate culture because it attributes to it a role in which many costs externalised by the company to society and to the planet, but in fact produced directly or indirectly by it. A correct cultural approach and greater familiarity, particularly with the issues of manufacturing processes and products that have no impact on the environment, can make companies truly responsible and conscious of their role. Corporate Responsibility diff...

  20. Reader response research in stylistics

    OpenAIRE

    Whiteley, S.; Canning, P.

    2017-01-01

    This article introduces the special issue. In it, we argue that research into reader response\\ud should be recognised as a vital aspect of contemporary stylistics, and we establish our focus\\ud on work which explicitly investigates such responses through the collection and analysis of\\ud extra-textual datasets. Reader response research in stylistics is characterised by a commitment\\ud to rigorous and evidence-based approaches to the study of readers’ interactions with and\\ud around texts, and...

  1. The 2010 Haiti earthquake response.

    Science.gov (United States)

    Raviola, Giuseppe; Severe, Jennifer; Therosme, Tatiana; Oswald, Cate; Belkin, Gary; Eustache, Eddy

    2013-09-01

    This article presents an overview of the mental health response to the 2010 Haiti earthquake. Discussion includes consideration of complexities that relate to emergency response, mental health and psychosocial response in disasters, long-term planning of systems of care, and the development of safe, effective, and culturally sound mental health services in the Haitian context. This information will be of value to mental health professionals and policy specialists interested in mental health in Haiti, and in the delivery of mental health services in particularly resource-limited contexts in the setting of disasters. Copyright © 2013 Elsevier Inc. All rights reserved.

  2. A novel operant conflict procedure using incrementing shock intensities to assess the anxiolytic and anxiogenic effects of drugs.

    Science.gov (United States)

    Evenden, John; Ross, Laurie; Jonak, Gerald; Zhou, Jin

    2009-05-01

    There is a need for novel anxiolytics, which are effective, but do not cause sedation, tolerance, and rebound anxiety on discontinuation. To investigate a procedure that can be used to assess these characteristics preclinically, rats were initially trained to press a lever at a high rate to obtain food. Once trained, periods of punishment were introduced in which electric shocks were superimposed. The intensity of these electric shocks was increased every 90 s from very low (0.01 mA) to sufficiently high to stop most subjects responding (0.4 mA), so that a complete rate/intensity function was obtained during each punishment period. The benzodiazepine, chlordiazepoxide, and two novel subtype-selective gamma-aminobutyric acid-A agonists, TP003 and TPA023, significantly increased response rates mildly suppressed by intermediate levels of electric shock without any effect on unpunished response rate. Two clinically anxiogenic agents, yohimbine and flumazenil, reduced the rate of punished responding. Aripiprazole and amphetamine reduced both punished and unpunished responding. Repeated treatment with diazepam 2.5 mg/kg daily for 15 days, initially markedly reduced unpunished response rates, but also increased punished response rates, an effect which became greater with repeated treatment. Abrupt cessation of diazepam treatment produced a reduction in punished responding. Diazepam (5 mg/kg daily) produced a greater reduction in unpunished responding, a smaller increase in punished responding, and a larger and longer lasting reduction in punished rates on withdrawal. In conclusion, the procedure detected anxiolytic and anxiogenic effects of drugs, and the sedative side effects, development of tolerance, and rebound-anxiety on discontinuation of a benzodiazepine. This procedure should have utility in the characterization of novel treatments of anxiety.

  3. Olfactory bulb encoding during learning under anesthesia

    Science.gov (United States)

    Nicol, Alister U.; Sanchez-Andrade, Gabriela; Collado, Paloma; Segonds-Pichon, Anne; Kendrick, Keith M.

    2014-01-01

    Neural plasticity changes within the olfactory bulb are important for olfactory learning, although how neural encoding changes support new associations with specific odors and whether they can be investigated under anesthesia, remain unclear. Using the social transmission of food preference olfactory learning paradigm in mice in conjunction with in vivo microdialysis sampling we have shown firstly that a learned preference for a scented food odor smelled on the breath of a demonstrator animal occurs under isofluorane anesthesia. Furthermore, subsequent exposure to this cued odor under anesthesia promotes the same pattern of increased release of glutamate and gamma-aminobutyric acid (GABA) in the olfactory bulb as previously found in conscious animals following olfactory learning, and evoked GABA release was positively correlated with the amount of scented food eaten. In a second experiment, multiarray (24 electrodes) electrophysiological recordings were made from olfactory bulb mitral cells under isofluorane anesthesia before, during and after a novel scented food odor was paired with carbon disulfide. Results showed significant increases in overall firing frequency to the cued-odor during and after learning and decreases in response to an uncued odor. Analysis of patterns of changes in individual neurons revealed that a substantial proportion (>50%) of them significantly changed their response profiles during and after learning with most of those previously inhibited becoming excited. A large number of cells exhibiting no response to the odors prior to learning were either excited or inhibited afterwards. With the uncued odor many previously responsive cells became unresponsive or inhibited. Learning associated changes only occurred in the posterior part of the olfactory bulb. Thus olfactory learning under anesthesia promotes extensive, but spatially distinct, changes in mitral cell networks to both cued and uncued odors as well as in evoked glutamate and GABA

  4. Water Soluble Responsive Polymer Brushes

    Directory of Open Access Journals (Sweden)

    Andrew J. Parnell

    2011-12-01

    Full Text Available Responsive polymer brushes possess many interesting properties that enable them to control a range of important interfacial behaviours, including adhesion, wettability, surface adsorption, friction, flow and motility. The ability to design a macromolecular response to a wide variety of external stimuli makes polymer brushes an exciting class of functional materials, and has been made possible by advances in modern controlled polymerization techniques. In this review we discuss the physics of polymer brush response along with a summary of the techniques used in their synthesis. We then review the various stimuli that can be used to switch brush conformation; temperature, solvent quality, pH and ionic strength as well as the relatively new area of electric field actuation We discuss examples of devices that utilise brush conformational change, before highlighting other potential applications of responsive brushes in real world devices.

  5. EPA’s Response Techniques

    Science.gov (United States)

    Done through 10 regional office and in close cooperation with a network of federal, state, and local governments. First they investigate the site, then determine response alternatives and safety measures, considering hazards and exposure pathways.

  6. GBM Response Matrix FITS Files

    Data.gov (United States)

    National Aeronautics and Space Administration — Time-dependent detector response matrices for each GBM detector covering the duration of every GBM flare. Needed in the spectral analysis software to relate observed...

  7. Response to marine oil spills

    International Nuclear Information System (INIS)

    1987-01-01

    This book reviews the problems posed by marine oil spills and the practical response measures which can be implemented. Aspects discussed include containment and recovery, the use of dispersants, shoreline clean-up and planning and operations. (UK)

  8. Dapsone responsive juvenile pemphigus foliaceus

    Directory of Open Access Journals (Sweden)

    Gautam R

    1994-01-01

    Full Text Available An 8-year-old girl of Pemphigus foliaceus is reported because of the rarity of the condition in childhood. The disease was resistant to steroids and showed a dramatic response to dapsone.

  9. Mapping "Social Responsibility" in Science

    DEFF Research Database (Denmark)

    Horst, Maja; Glerup, Cecilie

    The paper investigates the discourse on social responsibility in science as it appears in academic journals. Through database searches a collection of more than 300 papers have been analysed in order to map their answers to the following three questions: - What is the central problem that threatens...... of social responsibility of science imply different forms of governance of and within science. The paper employs a Foucaldian discourse analysis to understand how a particular conceptualisation of responsibility implies a political rationality, i.e. a particular form of governance of science. The analysis...... responsibility in science? - What are the central aspects of science or its relation to society that need to be regulated or changed? - What kinds of solutions are imagined and how are these solutions supposed to be put into place? On this basis the paper explores how different interpretations of the notion...

  10. Identification of noisy response latency

    Science.gov (United States)

    Tamborrino, Massimiliano; Ditlevsen, Susanne; Lansky, Petr

    2012-08-01

    In many physical systems there is a time delay before an applied input (stimulation) has an impact on the output (response), and the quantification of this delay is of paramount interest. If the response can only be observed on top of an indistinguishable background signal, the estimation can be highly unreliable, unless the background signal is accounted for in the analysis. In fact, if the background signal is ignored, however small it is compared to the response and however large the delay is, the estimate of the time delay will go to zero for any reasonable estimator when increasing the number of observations. Here we propose a unified concept of response latency identification in event data corrupted by a background signal. It is done in the context of information transfer within a neural system, more specifically on spike trains from single neurons. The estimators are compared on simulated data and the most suitable for specific situations are recommended.

  11. Identification of noisy response latency

    DEFF Research Database (Denmark)

    Tamborrino, Massimiliano; Ditlevsen, Susanne; Lansky, Petr

    2012-01-01

    the number of observations. Here we propose a unified concept of response latency identification in event data corrupted by a background signal. It is done in the context of information transfer within a neural system, more specifically on spike trains from single neurons. The estimators are compared......In many physical systems there is a time delay before an applied input (stimulation) has an impact on the output (response), and the quantification of this delay is of paramount interest. If the response can only be observed on top of an indistinguishable background signal, the estimation can...... be highly unreliable, unless the background signal is accounted for in the analysis. In fact, if the background signal is ignored, however small it is compared to the response and however large the delay is, the estimate of the time delay will go to zero for any reasonable estimator when increasing...

  12. The Diffraction Response Interpolation Method

    DEFF Research Database (Denmark)

    Jespersen, Søren Kragh; Wilhjelm, Jens Erik; Pedersen, Peder C.

    1998-01-01

    Computer modeling of the output voltage in a pulse-echo system is computationally very demanding, particularly whenconsidering reflector surfaces of arbitrary geometry. A new, efficient computational tool, the diffraction response interpolationmethod (DRIM), for modeling of reflectors in a fluid ...

  13. The Phage Shock Protein Response.

    Science.gov (United States)

    Flores-Kim, Josué; Darwin, Andrew J

    2016-09-08

    The phage shock protein (Psp) system was identified as a response to phage infection in Escherichia coli, but rather than being a specific response to a phage, it detects and mitigates various problems that could increase inner-membrane (IM) permeability. Interest in the Psp system has increased significantly in recent years due to appreciation that Psp-like proteins are found in all three domains of life and because the bacterial Psp response has been linked to virulence and other important phenotypes. In this article, we summarize our current understanding of what the Psp system detects and how it detects it, how four core Psp proteins form a signal transduction cascade between the IM and the cytoplasm, and current ideas that explain how the Psp response keeps bacterial cells alive. Although recent studies have significantly improved our understanding of this system, it is an understanding that is still far from complete.

  14. Emotional response to musical repetition.

    Science.gov (United States)

    Livingstone, Steven R; Palmer, Caroline; Schubert, Emery

    2012-06-01

    Two experiments examined the effects of repetition on listeners' emotional response to music. Listeners heard recordings of orchestral music that contained a large section repeated twice. The music had a symmetric phrase structure (same-length phrases) in Experiment 1 and an asymmetric phrase structure (different-length phrases) in Experiment 2, hypothesized to alter the predictability of sensitivity to musical repetition. Continuous measures of arousal and valence were compared across music that contained identical repetition, variation (related), or contrasting (unrelated) structure. Listeners' emotional arousal ratings differed most for contrasting music, moderately for variations, and least for repeating musical segments. A computational model for the detection of repeated musical segments was applied to the listeners' emotional responses. The model detected the locations of phrase boundaries from the emotional responses better than from performed tempo or physical intensity in both experiments. These findings indicate the importance of repetition in listeners' emotional response to music and in the perceptual segmentation of musical structure.

  15. Linking Item Response Model Parameters.

    Science.gov (United States)

    van der Linden, Wim J; Barrett, Michelle D

    2016-09-01

    With a few exceptions, the problem of linking item response model parameters from different item calibrations has been conceptualized as an instance of the problem of test equating scores on different test forms. This paper argues, however, that the use of item response models does not require any test score equating. Instead, it involves the necessity of parameter linking due to a fundamental problem inherent in the formal nature of these models-their general lack of identifiability. More specifically, item response model parameters need to be linked to adjust for the different effects of the identifiability restrictions used in separate item calibrations. Our main theorems characterize the formal nature of these linking functions for monotone, continuous response models, derive their specific shapes for different parameterizations of the 3PL model, and show how to identify them from the parameter values of the common items or persons in different linking designs.

  16. Procedure for determining the SSE response from the OBE response

    International Nuclear Information System (INIS)

    Curreri, J.

    1985-01-01

    Regulatory Guide 1.61 specifies the damping that should be used for all modes that are considered in an elastic spectral or time history dynamic seismic analysis of Seismic Category I components. Table 1 of R.G 1.61 specifies damping values for dynamic analysis for two different earthquakes, the Safe Shutdown Earthquake and the Operating Basis Earthquake. The guide specifies that ''...if the maximum stresses due to static, seismic and other dynamic loading are significantly lower than the yield stresses and 1/2 yield stress for SSE and 1/2 SSE respectively, in any structure a component damping values lower than those specified in Table 1 ....should be used .... to avoid underestimating the amplitude of vibration of dynamic stress.'' The guide requires that the appropiate damping values be used which reflect the state of stress that will be experienced by the equipment. In applying these values to the response of equipment, to an OBE and to an SSE, the selected damping should result in a dynamic response for the SSE that is greater than the response due to the OBE, all other factors being equal. The purpose of the statement in the guide is to note that at higher stress levels, the higher damping values could be used, but at lower stress levels, the lower values of damping should be used. Current procedures that are used in implementing R.G. 1.61 frequently result in an OBE response that is greater than the SSE response. This is because the higher damping under the SSE is used at all stress levels, low as well as high. This is obviously not the intent of the Regulatory Guide. A procedure has been developed which derives an expression relating the SSE response to the OBE response. Two factors are involved in the equation. The first involves the damping ratios for the SSE and OBE events and the second is the ratio between the levels of the OBE and SSE

  17. The Diffraction Response Interpolation Method

    DEFF Research Database (Denmark)

    Jespersen, Søren Kragh; Wilhjelm, Jens Erik; Pedersen, Peder C.

    1998-01-01

    Computer modeling of the output voltage in a pulse-echo system is computationally very demanding, particularly whenconsidering reflector surfaces of arbitrary geometry. A new, efficient computational tool, the diffraction response interpolationmethod (DRIM), for modeling of reflectors in a fluid...... medium, is presented. The DRIM is based on the velocity potential impulseresponse method, adapted to pulse-echo applications by the use of acoustical reciprocity. Specifically, the DRIM operates bydividing the reflector surface into planar elements, finding the diffraction response at the corners...

  18. Haiti Earthquake: Crisis and Response

    Science.gov (United States)

    2010-02-19

    years ago, in 1860. Haitian ministries are addressing issues such as long-term housing for those left homeless by the earthquake as they operate out...CRS Report for Congress Prepared for Members and Committees of Congress Haiti Earthquake: Crisis and Response Rhoda Margesson... Crisis and Response 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER 5e. TASK NUMBER 5f. WORK

  19. Transcompartmental Inflammatory Responses in Humans

    DEFF Research Database (Denmark)

    Plovsing, Ronni R; Berg, Ronan M G; Evans, Kevin A

    2014-01-01

    OBJECTIVES: Transcompartmental signaling during early inflammation may lead to propagation of disease to other organs. The time course and the mechanisms involved are still poorly understood. We aimed at comparing acute transcompartmental inflammatory responses in humans following lipopolysacchar......OBJECTIVES: Transcompartmental signaling during early inflammation may lead to propagation of disease to other organs. The time course and the mechanisms involved are still poorly understood. We aimed at comparing acute transcompartmental inflammatory responses in humans following...

  20. Chernobyl: A policy response study

    International Nuclear Information System (INIS)

    Segerstahl, B.

    1991-01-01

    Chernobyl consists of a series of papers concerned with societal responses to the accident at Chernobyl. The book is composed of a series of segments that focus of aspects of the post-accident policy: monitoring and assessment, health effects, agriculture and trade, international responses, and the media and credibility crisis. Seven European countries were investigated for information on how they dealt with the accident

  1. Sustainable Materialisation of Responsive Architecture

    Directory of Open Access Journals (Sweden)

    Artem Holstov

    2017-03-01

    Full Text Available Natural organisms which employ inherent material properties to enable a passive dynamic response offer inspiration for adaptive bioclimatic architecture. This approach allows a move away from the technological intensity of conventional “smart” building systems towards a more autonomous and robust materially embedded sensitivity and climatic responsiveness. The actuation mechanisms of natural responsive systems can be replicated to produce artificial moisture-sensitive (hygromorphic composites with the response driven by hygroexpansion of wood. The work presented here builds on previous research on lab-scale material development, to investigate in detail the applicability of wood-based hygromorphic materials for large-scale external applications. The suitability of different material production techniques and viability of potential applications is established through a detailed programme of experimentation and the first one-year-long durability study of hygromorphic wood composites in full weathering conditions. These results provide the basis for the design of an optimised responsive cladding system. The opportunities and challenges presented by building integration and architectural functionalisation of responsive wood composites are discussed based on a hierarchy of application typologies including functional devices and components, performance-oriented adaptive systems, the value of aesthetic and spatial experience and place-specific contextual integration. The design of the first full-scale building application of hygromorphic wood composites is presented.

  2. West syndrome: response to valproate.

    Science.gov (United States)

    Chandra, Surabhi; Bhave, Anupama; Bhargava, Roli; Kumar, Chandrakanta; Kumar, Rashmi

    2012-01-01

    Management of West syndrome is unsatisfactory. In our clinic we observed that a significant proportion of patients respond to usual dose of valproate. To prospectively assess the efficacy of valproate in controlling infantile spasms in West syndrome. Consecutive patients presenting with West syndrome to the Pediatric Neurology Clinic or general outpatient department (OPD) were enrolled for study. Those who were not on any treatment were given valproate in a dose of 30 mg/kg/day while awaiting investigations. Patients were followed up every 2 weeks. Predefined criteria for definition of West syndrome and response were used. Those showing partial/poor response or relapse on valproate were given hormonal therapy. One hundred children with West syndrome were enrolled. Ninety one children were started on valproate. Of these 36 (39.5%) showed a good response, but seven later relapsed while on same dose of valproate and three were lost to follow up. Later age at onset and typical hypsarrhythmia on EEG were associated with good sustained response to valproate while a history of delayed cry at birth was associated with partial or poor response. Sixty two patients who responded poorly to or relapsed on valproate were put on hormonal treatment in addition. Of these 36 (58.1%) had a good response but 11 later relapsed after stopping treatment and two were lost to follow up. Valproate may have a role in treatment of West syndrome in a selected group of patients.

  3. West Syndrome: Response to valproate

    Directory of Open Access Journals (Sweden)

    Surabhi eChandra

    2012-11-01

    Full Text Available Management of West syndrome is unsatisfactory. In our clinic we observed that a significant proportion of patients respond to usual dose of valproate. Objective: To prospectively assess the efficacy of valproate in controlling infantile spasms in West syndromeMethods: Consecutive patients presenting with West syndrome to the Pediatric Neurology Clinic or general OPD were enrolled for study. Those who were not on any treatment were given valproate in a dose of 30 mg/kg/day while awaiting investigations. Patients were followed up every 2 weeks. Predefined criteria for definition of West syndrome and response were used. Those showing partial/poor response or relapse on valproate were given hormonal therapy.Results: One hundred children with West syndrome were enrolled. Ninety one children were started on valproate. Of these 36 (39.5% showed a good response, but 7 later relapsed while on same dose of valproate and 3 were lost to follow up. Later age at onset and typical hypsarrythmia on EEG were associated with good sustained response to valproate while a history of delayed cry at birth was associated with partial or poor response. Sixty two patients who responded poorly to or relapsed on valproate were put on hormonal treatment in addition. Of these 36 (58.1% had a good response but 11 later relapsed after stopping treatment and 2 were lost to follow up. Conclusions: Valproate may have a role in treatment of West syndrome in a selected group of patients.

  4. Complex responses to alkylating agents

    International Nuclear Information System (INIS)

    Samson, L.D.

    2003-01-01

    Using Affymetrix oligonucleotide GeneChip analysis, we previously found that, upon exposure to the simple alkylating agent methylmethane sulfonate, the transcript levels for about one third of the Saccharomyces cerevisiae genome (∼2,000 transcripts) are induced or repressed during the first hour or two after exposure. In order to determine whether the responsiveness of these genes has any relevance to the protection of cells against alkylating agents we have undertaken several follow-up studies. First, we explored the specificity of this global transcriptional response to MMS by measuring the global response of S. cerevisiae to a broad range of agents that are known to induce DNA damage. We found that each agent produced a very different mRNA transcript profile, even though the exposure doses produced similar levels of toxicity. We also found that the selection of genes that respond to MMS is highly dependent upon what cell cycle phase the cells are in at the time of exposure. Computational clustering analysis of the dataset derived from a large number of exposures identified several promoter motifs that are likely to control some of the regulons that comprise this large set of genes that are responsive to DNA damaging agents. However, it should be noted that these agents damage cellular components other than DNA, and that the responsiveness of each gene need not be in response to DNA damage per se. We have also begun to study the response of other organisms to alkylating agents, and these include E. coli, cultured mouse and human cells, and mice. Finally, we have developed a high throughput phenotypic screening method to interrogate the role of all non-essential S. cerevisiae genes (about 4,800) in protecting S. cerevisiae against the deleterious effects of alkylating agents; we have termed this analysis 'genomic phenotyping'. This study has uncovered a plethora of new pathways that play a role in the recovery of eukaryotic cells after exposure to toxic

  5. GABAergic transmission and chloride equilibrium potential are not modulated by pyruvate in the developing optic tectum of Xenopus laevis tadpoles.

    Directory of Open Access Journals (Sweden)

    Arseny S Khakhalin

    Full Text Available In the developing mammalian brain, gamma-aminobutyric acid (GABA is thought to play an excitatory rather than an inhibitory role due to high levels of intracellular Cl(- in immature neurons. This idea, however, has been questioned by recent studies which suggest that glucose-based artificial cerebrospinal fluid (ACSF may be inadequate for experiments on immature and developing brains. These studies suggest that immature neurons may require alternative energy sources, such as lactate or pyruvate. Lack of these other energy sources is thought to result in artificially high intracellular Cl(- concentrations, and therefore a more depolarized GABA receptor (GABAR reversal potential. Since glucose metabolism can vary widely among different species, it is important to test the effects of these alternative energy sources on different experimental preparations. We tested whether pyruvate affects GABAergic transmission in isolated brains of developing wild type Xenopus tadpoles in vitro by recording the responsiveness of tectal neurons to optic nerve stimulation, and by measuring currents evoked by local GABA application in a gramicidin perforated patch configuration. We found that, in contrast with previously reported results, the reversal potential for GABAR-mediated currents does not change significantly between developmental stages 45 and 49. Partial substitution of glucose by pyruvate had only minor effects on both the GABA reversal potential, and the responsiveness of tectal neurons at stages 45 and 49. Total depletion of energy sources from the ACSF did not affect neural responsiveness. We also report a strong spatial gradient in GABA reversal potential, with immature cells adjacent to the lateral and caudal proliferative zones having more positive reversal potentials. We conclude that in this experimental preparation standard glucose-based ACSF is an appropriate extracellular media for in vitro experiments.

  6. Evidence for pretreatment LICI deficits among depressed children and adolescents with nonresponse to fluoxetine.

    Science.gov (United States)

    Croarkin, Paul E; Nakonezny, Paul A; Husain, Mustafa M; Port, John D; Melton, Tabatha; Kennard, Betsy D; Emslie, Graham J; Kozel, F Andrew; Daskalakis, Zafiris J

    2014-01-01

    Research suggests that alterations in gamma-aminobutyric acid receptor functioning have a role in depression. Paired-pulse transcranial magnetic stimulation (TMS) paradigms are noninvasive measures of cortical inhibitory and excitatory circuits. The present study examined pretreatment short-interval intracortical inhibition (SICI), long-interval cortical inhibition (LICI), and intracortical facilitation (ICF) in children and adolescents with major depressive disorder who were initiating fluoxetine treatment. The primary objective was to examine the relationship of these measures with subsequent treatment response. It was hypothesized that alterations in pretreatment GABA and glutamate mediated neurotransmission, would be associated with fluoxetine nonresponse. Sixteen children and adolescents with major depressive disorder underwent paired-pulse TMS testing before beginning fluoxetine treatment. Response was prospectively characterized by scores of 1 or 2 on the Clinical Global Impression Scale and less than 40 on the Children's Depression Rating Scale-Revised after 6 weeks of fluoxetine treatment (20-40 mg/day). Eight patients responded to treatment. Least-squares mean LICI values were consistently higher bilaterally for treatment nonresponders. Higher LICI values indicate less inhibition and impaired GABAB functioning. There was no significant effect of treatment response on the measures of SICI and ICF. Our findings suggest that deficits in pretreatment GABAB may be related to fluoxetine nonresponse in depressed youth. This is congruent with prior work demonstrating that GABAB interneurons have serotonergic input and antidepressants modulate GABAB receptors. These findings also show that TMS paradigms have utility in studying the neurophysiology and treatment of childhood mood disorders. Cortical Excitability and Inhibition in Children and Adolescents With Major Depressive Disorder, http://www.clinicaltrials.gov/ct2/show/NCT00896090?term

  7. responsibility

    African Journals Online (AJOL)

    Activities of the Zimbabwean theatre are overseen by the Ministry of Sports, Recre- ation and Culture. ..... This fund is meant for Zimbabwean students who are interested in pursuing arts and culture related studies ..... Institute (ITI) and a Korean theatre Director who had declared in his international mes- sage for the day that.

  8. Response

    CERN Multimedia

    CERN. Geneva

    2015-01-01

    ALICE is the LHC experiment dedicated to the study of Heavy Ion collisions. In particular, the detector features low momentum tracking and vertexing, and comprehensive particle identification capabilities. In a single central heavy ion collision at the LHC, thousands of particles per unit rapidity are produced, making the data volume, track reconstruction and search of rare signals particularly challenging. Data science and machine learning techniques could help to tackle some of the challenges outlined above. In this talk, we will discuss some early attempts to use these techniques for the processing of detector signals and for the physics analysis. We will also highlight the most promising areas for the application of these methods.

  9. Response

    CERN Document Server

    CERN. Geneva

    2015-01-01

    Stochastic optimization, among which bio-inspired algorithms, is gaining momentum in areas where more classical optimization algorithms fail to deliver satisfactory results, or simply cannot be directly applied. This presentation will introduce baseline stochastic optimization algorithms, and illustrate their efficiency in different domains, from continuous non-convex problems to combinatorial optimization problem, to problems for which a non-parametric formulation can help exploring unforeseen possible solution spaces.

  10. Response

    Science.gov (United States)

    Hartman, Nancy C.

    1974-01-01

    Suggests more stringent use of task analysis in identifying and teaching reading subskills and the use of reinforcement contingencies which make it worthwhile for the child to tolerate frustration when teaching remedial reading to children with low frustration tolerance levels. (TO)

  11. Response

    CERN Multimedia

    CERN. Geneva

    2015-01-01

    Starting from a brief historical perspective on scientific discovery, this talk will review some of the theory and open problems of deep learning and describe how to design efficient feedforward and recursive deep learning architectures for applications in the natural sciences. In particular, the focus will be on multiple particle problems at different scales: in biology (e.g. prediction of protein structures), chemistry (e.g. prediction of molecular properties and reactions), and high-energy physics (e.g. detection of exotic particles, jet substructure and tagging, "dark matter and dark knowledge")

  12. Response

    CERN Multimedia

    CERN. Geneva

    2015-01-01

    Neuromorphic silicon chips have been developed over the last 30 years, inspired by the design of biological nervous systems and offering an alternative paradigm for computation, with real-time massively parallel operation and potentially large power savings with respect to conventional computing architectures. I will present the general principles with a brief investigation of the design choices that have been explored, and I'll discuss how such hardware has been applied to problems such as classification.

  13. Response spectra in alluvial soils

    International Nuclear Information System (INIS)

    Chandrasekharan, A.R.; Paul, D.K.

    1975-01-01

    For aseismic design of structures, the ground motion data is assumed either in the form of ground acceleration as a function of time or indirectly in the form of response spectra. Though the response spectra approach has limitations like not being applicable for nonlinear problems, it is usually used for structures like nuclear power plants. Fifty accelerograms recorded at alluvial sites have been processed. Since different empirical formulas relating acceleration with magnitude and distance give a wide scatter of values, peak ground acceleration alone cannot be the parameter as is assumed by a number of authors. The spectra corresponding to 5% damping have been normalised with respect to three parameters, namely, peak ground acceleration, peak ground velocity and a nondimensional quantity ad/v 2 . Envelopee of maxima and minima as well as average response spectra has been obtained. A comparison with the USAEC spectra has been made. A relation between ground acceleration, ground velocity and ad/v 2 has been obtained which would nearly give the same magnification of the response. A design response spectra for alluvial soils has been recommended. (author)

  14. Heart rate response to breathing

    DEFF Research Database (Denmark)

    Mehlsen, J; Pagh, K; Nielsen, J S

    1987-01-01

    Heart rate responses to stepwise and periodic changes in lung volume were studied in seven young healthy males. Stepwise inspiration and expiration both resulted in an increase in heart rate followed by a rapid decrease in heart rate. The fastest heart rate was reached in 1.6 +/- 0.5 s and in 3.......6 +/- 1.4 s in response to inspiration and expiration, respectively (P less than 0.01). The slowest heart rate was reached in 4.8 +/- 1.0 s and in 7.6 +/- 1.9 s in response to inspiration and expiration, respectively (P less than 0.01). Following this biphasic change the heart rate returned to a steady...... level. The difference between the fastest and the slowest heart rates was significantly larger in response to inspiration (21.7 +/- 7.3 beats per minute) than in response to expiration (12.0 +/- 7.3 beats per minute; P less than 0.01). Periodic changes in lung volume were performed with frequencies from...

  15. Response problems in a vacation panel study

    Science.gov (United States)

    Christine A. Vogt; Susan I. Stewart

    2001-01-01

    This paper investigates response problems encountered in a panel study of travel behavior. Though the overall response rate to the three-wave panel study was acceptable (over 60%), three types of response problems were encountered: refusal, non-response, and attrition. In a follow-up phone survey, a sample of individuals from each problem response group was questioned...

  16. Towards accurate emergency response behavior

    International Nuclear Information System (INIS)

    Sargent, T.O.

    1981-01-01

    Nuclear reactor operator emergency response behavior has persisted as a training problem through lack of information. The industry needs an accurate definition of operator behavior in adverse stress conditions, and training methods which will produce the desired behavior. Newly assembled information from fifty years of research into human behavior in both high and low stress provides a more accurate definition of appropriate operator response, and supports training methods which will produce the needed control room behavior. The research indicates that operator response in emergencies is divided into two modes, conditioned behavior and knowledge based behavior. Methods which assure accurate conditioned behavior, and provide for the recovery of knowledge based behavior, are described in detail

  17. Distributed Dynamic Condition Response Structures

    DEFF Research Database (Denmark)

    Hildebrandt, Thomas; Mukkamala, Raghava Rao

    We present distributed dynamic condition response structures as a declarative process model inspired by the workflow language employed by our industrial partner and conservatively generalizing labelled event structures. The model adds to event structures the possibility to 1) finitely specify...... repeated, possibly infinite behavior, 2) finitely specify fine-grained acceptance conditions for (possibly infinite) runs based on the notion of responses and 3) distribute events via roles. We give a graphical notation inspired by related work by van der Aalst et al and formalize the execution semantics...... as a labelled transition system. Exploration of the relationship between dynamic condition response structures and traditional models for concurrency, application to more complex scenarios, and further extensions of the model is left to future work....

  18. Delayed response in ipilimumab therapy.

    Science.gov (United States)

    Megahed, Ahmed; Faulhaber, Peter; Phillips, Tycel; Koon, Henry

    2014-03-01

    Metastatic melanoma is a deadly disease with a 5-year survival rate lower than 20%. In 2011, ipilimumab, a fully humanized antibody that binds to cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) was approved by the US Food and Drug Administration based on improved survival in a pivotal trial. CTLA4 is a molecule on cytotoxic T-lymphocytes that plays a critical role in attenuating immune responses. Ipilimumab blocks the binding of B7, the ligand of CTLA4, thereby blocking the activation of CTLA4 and sustaining antitumor immune responses. The time course to response can be variable with immunotherapeutics. We report on a patient who experienced a considerable delay before responding to ipilimumab.

  19. Risk, responsibility and political action

    DEFF Research Database (Denmark)

    Halskov Jensen, Elisabeth

    2004-01-01

    . It is argued that an application of the Toulmin model is useful for eliciting systematic overall repre-sentations of responsibility and agency in environmental crises such as the mad cow crisis as well as for revealing relationships between social domains such as moral, politics, economics and science......ABSTRACT. This paper presents an argumentative case study of the discursive representation of risk, responsibility and political action in the Spanish media. The study uses a critical discourse analytical approach combined with theories on risk, agency and political communication in the media...... action was transformed into a moral respon-sibility on the part of the national and European politicians, constrained by economic and technical-scientific reality and represented as taking place only in the public sphere. KEY WORDS: CDA, World Risk Society, argumentation, media discourse, argumentation...

  20. Risk, responsibility and political action

    DEFF Research Database (Denmark)

    Halskov Jensen, Elisabeth

    2004-01-01

    ABSTRACT. This paper presents an argumentative case study of the discursive representation of risk, responsibility and political action in the Spanish media. The study uses a critical discourse analytical approach combined with theories on risk, agency and political communication in the media....... It is argued that an application of the Toulmin model is useful for eliciting systematic overall repre-sentations of responsibility and agency in environmental crises such as the mad cow crisis as well as for revealing relationships between social domains such as moral, politics, economics and science...... in discourse. Discourse analysis shows that in the Spanish newspaper sample the focus was on the construal of high risk and on the construal of the national Spanish politicians, the EU and the Brit-ish nation as scapegoats. No responsibility was associated with consumers or other individual players. Political...

  1. Nonlocal Response in Plasmonic Nanostructures

    DEFF Research Database (Denmark)

    Wubs, Martijn; Mortensen, N. Asger

    2016-01-01

    After a brief overview of nanoplasmonics experiments that defy explanation with classical electrodynamics, we introduce nonlocal response as a main reason for non-classical effects. This concept is first introduced phenomenologically, and afterwards based on the semi-classical hydrodynamic Drude...... model (HDM) that indeed exhibits nonlocal response. In particular, we discuss recent generalizations and extensions of the HDM, to include both convection and diffusion dynamics of the induced charges. This generalized nonlocal optical response (GNOR) model allows for the first time unified semi-classical...... explanations of known experimental phenomena for both monomers and dimers that previously seemed to require microscopic theory. Finally, we turn to Landau damping and discuss the microscopic origin of the size-dependent damping captured by the classical diffusion mechanism in the GNOR model....

  2. Small Business Social Responsibility Communication

    DEFF Research Database (Denmark)

    Morsing, Mette; Spence, Laura J.

    2015-01-01

    Purpose: Corporate social responsibility communication by small and medium sized enterprises is theorized to form the concept of Small Business Social Responsibility (SBSR) Communication. Design/methodology/approach: This is a conceptual paper that draws on Foucault’s theory of governmentality...... to conceptualization of SBSR communication as we develop a framework which suggests a spectrum of disciplining effects of social responsibility in relation to implicit and explicit CSR. We analyse these from the perspectives of surveillance, examination and normalization. Research limitations...... of conduct and CSR reporting (i.e. CSR as a “regime of truth”, Foucault) and an internally prescribed ethos of a personal philosophy of ethics and norms such as family identity and employee values, concern for local community and legacy of the company (i.e. CSR as personally held values). We contribute...

  3. Abiotic stressors and stress responses

    DEFF Research Database (Denmark)

    Sulmon, Cecile; Van Baaren, Joan; Cabello-Hurtado, Francisco

    2015-01-01

    life history traits of stressed organisms, and ii) to what extent trait responses influence individual and population responses. Common response mechanisms are evident at molecular and cellular scales but become rather difficult to define at higher levels due to evolutionary distance and environmental......Abstract Organisms are regularly subjected to abiotic stressors related to increasing anthropogenic activities, including chemicals and climatic changes that induce major stresses. Based on various key taxa involved in ecosystem functioning (photosynthetic microorganisms, plants, invertebrates), we...... review how organisms respond and adapt to chemical- and temperature-induced stresses from molecular to population level. Using field-realistic studies, our integrative analysis aims to compare i) how molecular and physiological mechanisms related to protection, repair and energy allocation can impact...

  4. Assessing Gravitropic Responses in Arabidopsis.

    Science.gov (United States)

    Barker, Richard; Cox, Benjamin; Silber, Logan; Sangari, Arash; Assadi, Amir; Masson, Patrick

    2016-01-01

    Arabidopsis thaliana was the first higher organism to have its genome sequenced and is now widely regarded as the model dicot. Like all plants, Arabidopsis develops distinct growth patterns in response to different environmental stimuli. This can be seen in the gravitropic response of roots. Methods to investigate this particular tropism are presented here. First, we describe a high-throughput time-lapse photographic analysis of root growth and curvature response to gravistimulation allowing the quantification of gravitropic kinetics and growth rate at high temporal resolution. Second, we present a protocol that allows a quantitative evaluation of gravitropic sensitivity using a homemade 2D clinostat. Together, these approaches allow an initial comparative analysis of the key phenomena associated with root gravitropism between different genotypes and/or accessions.

  5. Corporate Social Responsibility in Aviation

    Science.gov (United States)

    Phillips, Edwin D.

    2006-01-01

    The dialog within aviation management education regarding ethics is incomplete without a discussion of corporate social responsibility (CSR). CSR research requires discussion involving: (a) the current emphasis on CSR in business in general and aviation specifically; (b) business and educational theory that provide a basis for aviation companies to engage in socially responsible actions; (c) techniques used by aviation and aerospace companies to fulfill this responsibility; and (d) a glimpse of teaching approaches used in university aviation management classes. The summary of this research suggests educators explain CSR theory and practice to students in industry and collegiate aviation management programs. Doing so extends the discussion of ethical behavior and matches the current high level of interest and activity within the aviation industry toward CSR.

  6. Conditional autonomy and responsible Action: A response to Yusef ...

    African Journals Online (AJOL)

    way of making sense of some of the conceptual and pragmatic links between academic freedom and institutional autonomy. Nevertheless Waghid critiques Hall's uncritical treatment of prominent theoretical positions for his claims, which Waghid thinks leaves some of Hall's arguments truncated. This response finds Hall's ...

  7. Response shift en retrospectie. / Response shift in retrospect.

    NARCIS (Netherlands)

    Hoogstraten, J.; de Meijer, E.; Sprangers, M.

    1986-01-01

    Discusses the relationship between response shift and the concept of "artifact" with reference to W. K. Hofstee's (1986) arguments. The use of retrospective posttests instead of retrospective pretests is rejected, and some empirical approaches for assessing the impact of social desirability and

  8. Regulation of plant stress response by dehydration responsive ...

    African Journals Online (AJOL)

    Plant growth and productivity are greatly affected by environmental stresses such as dehydration, high salinity, low temperature and biotic pathogen infection. Plant adaptation to these environmental stresses is controlled by cascades of molecular networks. The dehydration responsive element binding (DREB) transcription ...

  9. Predicting Responses to Contemporary Environmental Change Using Evolutionary Response Architectures.

    Science.gov (United States)

    Bay, Rachael A; Rose, Noah; Barrett, Rowan; Bernatchez, Louis; Ghalambor, Cameron K; Lasky, Jesse R; Brem, Rachel B; Palumbi, Stephen R; Ralph, Peter

    2017-05-01

    Rapid environmental change currently presents a major threat to global biodiversity and ecosystem functions, and understanding impacts on individual populations is critical to creating reliable predictions and mitigation plans. One emerging tool for this goal is high-throughput sequencing technology, which can now be used to scan the genome for signs of environmental selection in any species and any system. This explosion of data provides a powerful new window into the molecular mechanisms of adaptation, and although there has been some success in using genomic data to predict responses to selection in fields such as agriculture, thus far genomic data are rarely integrated into predictive frameworks of future adaptation in natural populations. Here, we review both theoretical and empirical studies of adaptation to rapid environmental change, focusing on areas where genomic data are poised to contribute to our ability to estimate species and population persistence and adaptation. We advocate for the need to study and model evolutionary response architectures, which integrate spatial information, fitness estimates, and plasticity with genetic architecture. Understanding how these factors contribute to adaptive responses is essential in efforts to predict the responses of species and ecosystems to future environmental change.

  10. Counterconditioned Fear Responses Exhibit Greater Renewal than Extinguished Fear Responses

    Science.gov (United States)

    Holmes, Nathan M.; Leung, Hiu T.; Westbrook, R. Frederick

    2016-01-01

    This series of experiments used rats to compare counterconditioning and extinction of conditioned fear responses (freezing) with respect to the effects of a context shift. In each experiment, a stimulus was paired with shock in context A, extinguished or counterconditioned through pairings with sucrose in context B, and then tested for renewal…

  11. Response: Critical Realism--Response to Longhofer and Floersch

    Science.gov (United States)

    Briar-Lawson, Katharine

    2012-01-01

    This article addresses key challenges posed by critical realism, proposed by Longhofer and Floersch, as a philosophical underpinning for a science of social work. As a response to Longhofer and Floersch, it is argued that critical realism may be instructive in debates about structural conditions that dictate more inclusive interventions and…

  12. "Responsibility in Mobility": International Students and Social Responsibility

    Science.gov (United States)

    Tran, Ly Thi; Vu, Thao Thi Phuong

    2017-01-01

    Enhancing the educational experience and social connectedness for international students is the responsibility of different involved parties among whom international students themselves and host institutions play a key role. However, the question of how the condition of cross-border mobility has shaped and re-shaped international students'…

  13. The path to corporate responsibility.

    Science.gov (United States)

    Zadek, Simon

    2004-12-01

    Nike's tagline,"Just do it," is an inspirational call to action for the millions who wear the company's athletic gear. But in terms of corporate responsibility, Nike didn't always follow its own advice. In the 1990s, protesters railed against sweatshop conditions at some of its overseas suppliers and made Nike the global poster child for corporate ethical fecklessness. The intense pressure that activists exerted on the athletic apparel giant forced it to take a long, hard look at corporate responsibility--sooner than it might have otherwise. In this article, Simon Zadek, CEO of the UK-based institute AccountAbility, describes the bumpy route Nike has traveled to get to a better ethical place, one that cultivates and champions responsible business practices. Organizations learn in unique ways, Zadek contends, but they inevitably pass through five stages of corporate responsibility, from defensive ("It's not our fault") to compliance ("We'll do only what we have to") to managerial ("It's the business") to strategic ("It gives us a competitive edge") and, finally, to civil ("We need to make sure everybody does it"). He details Nike's arduous trek through these stages-from the company's initial defensive stance, when accusations about working conditions arose, all the way to its engagement today in the international debate about business's role in society and in public policy. As he outlines this evolution, Zadek offers valuable insights to executives grappling with the challenge of managing responsible business practices. Beyond just getting their own houses in order, the author argues, companies need to stay abreast of the public's evolving ideas about corporate roles and responsibilities. Organizations that do both will engage in what he calls"civil learning".

  14. IPCC SRES revisited: a response

    International Nuclear Information System (INIS)

    Nakicenovic, Nebojsa; Gruebler, A.; Gaffin, S.

    2003-01-01

    This article gives details of the response to the criticism of the Special Report on Emission Scenarios (SRES) and of some aspects of IPCC assessments. The criticism claims that market exchange rates (MER) were used instead of purchasing power parities (PPP) and that scenarios using Gross Domestic Product (GDP) growth in developing regions were flawed. Points raised in the response included that scenarios of GDP growth are typically expressed as MER, that the IPCC scenarios did include PPP-based scenarios, and that long-term emissions are based on more than just economic growth

  15. Electromagnetic responses of relativistic electrons

    Science.gov (United States)

    de Carvalho, C. A. A.; Reis, D. M.

    2018-02-01

    We compute the real and imaginary parts of the electric permittivities and magnetic permeabilities of relativistic electrons from quantum electrodynamics at finite temperatures and densities, for weak fields, neglecting electron-electron interactions. For non-zero temperatures, electromagnetic responses are reduced to one-dimensional integrals computed numerically. For zero temperature, we find analytic expressions for both their real/dispersive and imaginary/absorptive parts. As an application of our results, we obtain the dispersion relation for longitudinal electric plasmons. Present calculations support our recent claim that, at low frequencies and long wavelengths, the system will exhibit simultaneously negative electric and magnetic responses.

  16. Transcompartmental Inflammatory Responses in Humans

    DEFF Research Database (Denmark)

    Plovsing, Ronni R; Berg, Ronan M G; Evans, Kevin A

    2014-01-01

    OBJECTIVES: Transcompartmental signaling during early inflammation may lead to propagation of disease to other organs. The time course and the mechanisms involved are still poorly understood. We aimed at comparing acute transcompartmental inflammatory responses in humans following...... lipopolysaccharide-induced pulmonary and systemic inflammation. DESIGN: Randomized, double-blind, placebo-controlled, crossover study. SETTING ICU SUBJECTS: Healthy male volunteers. INTERVENTIONS: Fifteen volunteers (mean age, 23; SD, 2 yr) received Escherichia coli endotoxin (lipopolysaccharide, 4 ng/kg) IV...... measured. MEASUREMENTS AND MAIN RESULTS: IV endotoxin elicited a systemic inflammatory response with a time-dependent increase and peak in tumor necrosis factor-α, interleukin-6, and leukocyte counts (all p

  17. Designing a responsive web site

    OpenAIRE

    Fejzić , Diana

    2016-01-01

    Due to the increasing prevalence of smartphones and tablet computers design became a crucial part of web design. For a user, responsive web design enables the best user experience, regardless of whether a user is visiting the site via a mobile phone, a tablet or a computer. This thesis covers the process of planning, designing and responsive web site development, for a fictitious company named “Creative Design d.o.o.”, with the help of web technologies. In the initial part of the thesis, w...

  18. IPCC SRES revisited: a response

    Energy Technology Data Exchange (ETDEWEB)

    Nakicenovic, Nebojsa; Gruebler, A.; Gaffin, S. (and others)

    2003-07-01

    This article gives details of the response to the criticism of the Special Report on Emission Scenarios (SRES) and of some aspects of IPCC assessments. The criticism claims that market exchange rates (MER) were used instead of purchasing power parities (PPP) and that scenarios using Gross Domestic Product (GDP) growth in developing regions were flawed. Points raised in the response included that scenarios of GDP growth are typically expressed as MER, that the IPCC scenarios did include PPP-based scenarios, and that long-term emissions are based on more than just economic growth.

  19. Response to cardiac resynchronization therapy

    DEFF Research Database (Denmark)

    Versteeg, Henneke; Schiffer, Angélique A; Widdershoven, Jos W

    2009-01-01

    Cardiac resynchronization therapy (CRT) is a promising treatment for a subgroup of patients with advanced congestive heart failure and a prolonged QRS interval. Despite the majority of patients benefiting from CRT, 10-40% of patients do not respond to this treatment and are labeled as nonresponders....... Given that there is a lack of consensus on how to define response to CRT, the purpose of this viewpoint is to discuss currently used definitions and their shortcomings, and to provide recommendations as to how an expansion of the criteria for CRT response may be useful to clinicians....

  20. Predicting response to epigenetic therapy

    DEFF Research Database (Denmark)

    Treppendahl, Marianne B; Kristensen, Lasse S; Grønbæk, Kirsten

    2014-01-01

    Drugs targeting the epigenome are new promising cancer treatment modalities; however, not all patients receive the same benefit from these drugs. In contrast to conventional chemotherapy, responses may take several months after the initiation of treatment to occur. Accordingly, identification...... of good pretreatment predictors of response is of great value. Many clinical parameters and molecular targets have been tested in preclinical and clinical studies with varying results, leaving room for optimization. Here we provide an overview of markers that may predict the efficacy of FDA- and EMA...

  1. The Social Responsibility of Enterprises

    DEFF Research Database (Denmark)

    Rosdahl, Anders

    One of the main themes in the research program concerns the social responsibility of enterprises. The present working paper discusses this concept from a number of different angles. The working paper is part of process aimed at clarifying what may be meant by social responsibility of enterprises....... In the paper both common sense conceptions, sociological and economic perspectives are indicated. The conclusion is that the research program must take a social and labour market oriented conception as its point of departure and that both rational choice and cultural perspectives should be considered...

  2. Partiality of Responsibility: Ethics in Sustainability Consulting

    NARCIS (Netherlands)

    Earhart, R.S.

    2011-01-01

    Sustainability, Socially Responsible Investment (SRI) and Corporate Social Responsibility (CSR) are both highly normative fields of professional practice, framed by various narratives: capitalist versus environmentalist, waste versus respect for the planet, consumerism versus responsibility;

  3. Responses of plants to air pollution

    National Research Council Canada - National Science Library

    Mudd, J. Brian; Kozlowski, T. T

    1975-01-01

    .... KOZLOWSKI Pollution, 1975 ELROY L. RICE. Allelopathy, (Eds.). Fire and Ecosystems, 1974 (Eds.). Responses of Plants to Air Responses of Plants to Air PollutionRESPONSES OF PLANTS TO AIR POLLUTION E...

  4. Role of nicotinic receptors and acetylcholine in mucous cell metaplasia, hyperplasia and airway mucus formation in vitro and in vivo

    Science.gov (United States)

    Gundavarapu, Sravanthi; Wilder, Julie A.; Mishra, Neerad C.; Rir-sima-ah, Jules; Langley, Raymond J.; Singh, Shashi P.; Saeed, Ali Imran; Jaramillo, Richard J.; Gott, Katherine M.; Peña-Philippides, Juan Carlos; Harrod, Kevin S.; McIntosh, J. Michael; Buch, Shilpa; Sopori, Mohan L.

    2012-01-01

    Background Airway mucus hypersecretion is a key pathophysiological feature in number of lung diseases. Cigarette smoke/nicotine and allergens are strong stimulators of airway mucus; however, the mechanism of mucus modulation is unclear. Objectives Characterize the pathway by which cigarette smoke/nicotine regulates airway mucus and identify agents that decrease airway mucus. Methods IL-13 and gamma-aminobutyric acid receptors (GABAARs) are implicated in airway mucus. We examined the role of IL-13 and GABAARs in nicotine-induced mucus formation in normal human bronchial epithelial (NHBE) and A549 cells, and secondhand cigarette smoke and/or ovalbumin-induced mucus formation in vivo. Results Nicotine promotes mucus formation in NHBE cells; however, the nicotine-induced mucus formation is independent of IL-13 but sensitive to the GABAAR antagonist picrotoxin (PIC). Airway epithelial cells express α7/α9/α10 nicotinic acetylcholine receptors (nAChRs) and specific inhibition or knockdown of α7- but not α9/α10-nAChRs abrogates mucus formation in response to nicotine and IL-13. Moreover, addition of acetylcholine or inhibition of its degradation increases mucus in NHBE cells. Nicotinic but not muscarinic receptor antagonists block allergen or nicotine/cigarette smoke-induced airway mucus formation in NHBE cells and/or in mouse airways. Conclusions Nicotine-induced airway mucus formation is independent of IL-13 and α7-nAChRs are critical in airway mucous cell metaplasia/hyperplasia and mucus production in response to various pro-mucoid agents, including IL-13. In the absence of nicotine, acetylcholine may be the biological ligand for α7-nAChRs to trigger airway mucus formation. α7-nAChRs are downstream of IL-13 but upstream of GABAARα2 in the MUC5AC pathway. Acetylcholine and α-7-nAChRs may serve as therapeutic targets to control airway mucus. PMID:22578901

  5. Rapid Nongenomic Glucocorticoid Actions in Male Mouse Hypothalamic Neuroendocrine Cells Are Dependent on the Nuclear Glucocorticoid Receptor

    Science.gov (United States)

    Nahar, Jebun; Haam, Juhee; Chen, Chun; Jiang, Zhiying; Glatzer, Nicholas R.; Muglia, Louis J.; Dohanich, Gary P.; Herman, James P.

    2015-01-01

    Corticosteroids act classically via cognate nuclear receptors to regulate gene transcription; however, increasing evidence supports rapid, nontranscriptional corticosteroid actions via activation of membrane receptors. Using whole-cell patch clamp recordings in hypothalamic slices from male mouse genetic models, we tested for nongenomic glucocorticoid actions at glutamate and gamma aminobutyric acid (GABA) synapses in hypothalamic neuroendocrine cells, and for their dependence on the nuclear glucocorticoid receptor (GR). In enhanced green fluorescent protein-expressing CRH neurons of the paraventricular nucleus (PVN) and in magnocellular neurons of the PVN and supraoptic nucleus (SON), dexamethasone activated postsynaptic membrane-associated receptors and G protein signaling to elicit a rapid suppression of excitatory postsynaptic inputs, which was blocked by genetic deletion of type I cannabinoid receptors and a type I cannabinoid receptor antagonist. In magnocellular neurons, dexamethasone also elicited a rapid nitric oxide-dependent increase in inhibitory postsynaptic inputs. These data indicate a rapid, synapse-specific glucocorticoid-induced retrograde endocannabinoid signaling at glutamate synapses and nitric oxide signaling at GABA synapses. Unexpectedly, the rapid glucocorticoid effects on both excitatory and inhibitory synaptic transmission were lost with conditional deletion of GR in the PVN and SON in slices from a single minded-1-cre-directed conditional GR knockout mouse. Thus, the nongenomic glucocorticoid actions at glutamate and GABA synapses on PVN and SON neuroendocrine cells are dependent on the nuclear GR. The nuclear GR, therefore, is responsible for transducing the rapid steroid response at the membrane, or is either a critical component in the signaling cascade or regulates a critical component of the signaling cascade of a distinct membrane GR. PMID:26061727

  6. Contribution of the GABA shunt to hypoxia-induced alanine accumulation in roots of Arabidopsis thaliana.

    Science.gov (United States)

    Miyashita, Yo; Good, Allen G

    2008-01-01

    When subjected to low oxygen stress, plants accumulate alanine and gamma-aminobutyric acid (GABA). To investigate the function of GABA metabolism under hypoxia and its contribution to alanine accumulation, we studied the genes that encode the two key enzymes of the GABA shunt, glutamate decarboxylase (GAD) and GABA transaminase (GABA-T). Among the five homologous GAD genes found in Arabidopsis thaliana, GAD1 expression was predominantly found in roots, while GAD2 expression was evident in all organs. Expression of the other three GAD genes was generally weak. In response to hypoxia, transcriptional induction was observed for GAD4 only. For GABA-T1, its expression was detected in all organs, but there was no significant transcriptional change under hypoxic conditions. Moreover, we have isolated and characterized Arabidopsis mutants defective in GAD1 and GABA-T1. In gad1 mutants, GAD activity was significantly reduced in roots but was not affected in shoots. In the gaba-t1 mutant, GABA-T activity was decreased to negligible levels in both shoots and roots. These mutants were phenotypically normal under normal growth conditions except for the reduced seed production of the pop2 mutants as described previously. However, metabolite analysis revealed significant changes in GABA content in gad1 and gaba-t1 mutants. The levels of alanine under hypoxic conditions were also affected in the roots of gad1 and gaba-t1 mutants. The partial inhibition of the hypoxia-induced alanine accumulation in roots of these mutants suggests that the GABA shunt is, in part, responsible for the alanine accumulation under hypoxia.

  7. Tensions of Corporate Social Responsibility

    DEFF Research Database (Denmark)

    Strand, Robert

    I engaged with the top management team (TMT) and employees of American Cafes Corporation as an action/intervention researcher in the 20 months immediately following the TMT’s decision to formalize the company’s corporate social responsibility (CSR) activities. This led to the establishment...

  8. Causation and International State Responsibility

    NARCIS (Netherlands)

    Castellanos-Jankiewicz, L.

    2012-01-01

    This work studies causation in the law of international State responsibility. It is submitted that the absence of causation as an element of the internationally wrongful act owes more to the structure of international law, than to the inadequateness of causation as a conceptual and legal construct

  9. Being a potentially responsible party

    International Nuclear Information System (INIS)

    Ronan, J.T.

    1989-01-01

    This paper reports on CERCLA II- ability for the unlucky potentially responsible parties (PRPs) which is a Draconian form of strict, joint and several liability with limited statutory defenses that in most cases are impossible to establish. CERCLA vigorously employs these legal concepts, stretching a PRP's financial exposure to the limits necessary to meet the enormous financial costs of remediation

  10. A Responsive Cyber Risk Ecosystem

    Science.gov (United States)

    2017-01-19

    Functional Mission Analysis (FMA) is a disciplined way to tease out these linkages and integrate that metadata into our reporting systems and...UNCLASSIFIED - Distribution A: Approved for public release; distribution unlimited AIR FORCE CYBERWORX REPORT 16-003: A RESPONSIVE CYBER RISK...facilitated design thinking sessions that bring stakeholders , industry and academic experts together to develop solutions to hard problems. These

  11. Green taxation and individual responsibility

    Energy Technology Data Exchange (ETDEWEB)

    Ballet, Jerome [C3ED Centre of Economics and Ethics for Environment and Development, UVSQ, University of Versailles, Saint-Quentin-en-Yvelines (France); Bazin, Damien [EMAFI Macroeconomics and International Finance Research Centre at University of Nice Sophia Antipolis, 28, avenue Valrose, BP 2135, 06103 Nice (France); Lioui, Abraham [Department of Economics, Bar Ilan University, Ramat Gan (Israel); Touahri, David [LEST Institute of Labor Econmics and Industrial Sociology and Mediterranean University Aix-Marseille II, Marseille (France)

    2007-09-15

    The current article aims at studying the effects of taxation on environmental quality, in an economy where its agents are responsible. Individual responsibility towards nature is modelized by the voluntary effort to which the households have agreed insofar as the improvement of environmental quality is concerned. It is an original way to show that the individuals may feel committed towards the environment and assume obligations towards it as well as towards environmental public policy. Given that, in our model, such effort is taken from one's allocated time for leisure, its opportunity cost is that of the sacrificed time for leisure, and is therefore equal to the individual's wage. We shall highlight that State intervention through the introduction of a (green) tax always crowds out individual responsibility. However, the intensity of this crowding-out depends on the performance of the State. Moreover, State intervention could, depending on the amount of crowding-out, reduce the overall quality of the environment. In a general equilibrium setting, we show that the crowding-out effect is not systematic. This is because there will then be an interaction between effort (or work time) and the cost of that effort (linked to the individual's wage, and therefore to production and finally to work/effort). In this article, we shall discuss the conditions under which public policy crowds out individual responsibility within this context. (author)

  12. Corporate Social Responsibility for Sustainability

    Directory of Open Access Journals (Sweden)

    Wojciech Przychodzeń

    2014-06-01

    Full Text Available Purpose: The purpose of this paper is to is to provide insights on implementing corporate social responsibility for sustainability (CSRS concept and show how it differs from basic corporate social responsibility (CSR. Methodology: The paper discusses major issues with references to existing literature and real business cases from S&P500 consumer discretionary sector. Findings: The main fi nding of this paper is that CSRS could provide the company with a competitive advantage as a growing number of consumers become more sustainable conscious. It could also help to overcome the increasing consumers’ skepticism towards corporate social responsibility practices. Finally, it can also be seen as a step forward in defi ning what types of corporate activities are associated with desirable social and environmental gains. Research limitations: Our sample was restricted to the U.S. fi rms from the consumer discretionary sector. Therefore, conclusions should not be generalized to other markets. Our study is based on the analysis of environmental and social responsibility statements and assumes that they accurately represent corporate commitment in majority of the cases. Practical implications: CSRS offers corporations the opportunity to use their unique skills, culture, values, resources, and management capabilities to lead social progress by making sustainability part of its internal corporate logic. Originality: The paper raises the importance of the different conditions necessary for making sustainable development concept an important part of corporate strategy.

  13. Elementary School Philosophy: A Response

    Science.gov (United States)

    Wartenberg, Thomas E.

    2012-01-01

    This article is a response to criticism of my book "Big Ideas for Little Kids." The main topics addressed are: Who is the audience for the book? Can people without formal philosophical training can be good facilitators of elementary school philosophy discussions? Is it important to assess attempts to teach philosophy in elementary school? Should…

  14. Caenorhabditis elegans response to salt

    NARCIS (Netherlands)

    O.O. Umuerri (Oluwatoroti Omowayewa)

    2012-01-01

    textabstractThis thesis describes my work, where I used genetic methods to identify new genes involved in salt taste in C. elegans. In addition, I used calcium imaging to characterize the cellular response of C. elegans to salt. The thesis is divided into five sections and each section is summarized

  15. SICOEM: emergency response data system

    International Nuclear Information System (INIS)

    Martin, A.; Villota, C.; Francia, L.

    1993-01-01

    The main characteristics of the SICOEM emergency response system are: -direct electronic redundant transmission of certain operational parameters and plant status informations from the plant process computer to a computer at the Regulatory Body site, - the system will be used in emergency situations, -SICOEM is not considered as a safety class system. 1 fig

  16. SICOEM: emergency response data system

    Energy Technology Data Exchange (ETDEWEB)

    Martin, A.; Villota, C.; Francia, L. (UNESA, Madrid (Spain))

    1993-01-01

    The main characteristics of the SICOEM emergency response system are: -direct electronic redundant transmission of certain operational parameters and plant status informations from the plant process computer to a computer at the Regulatory Body site, - the system will be used in emergency situations, -SICOEM is not considered as a safety class system. 1 fig.

  17. Responsibilities in Studying Postmodern Families.

    Science.gov (United States)

    Bernardes, Jon

    1993-01-01

    Sees traditional modernist family sociology as oppressive and reactionary. To examine responsibilities of those who study postmodern family life, explores recent material with regard to theoretical, methodological, and policy-related issues. Links sociological practice, everyday practice, and policy formation. Argues that family professionals must…

  18. Vibration response of misaligned rotors

    Science.gov (United States)

    Patel, Tejas H.; Darpe, Ashish K.

    2009-08-01

    Misalignment is one of the common faults observed in rotors. Effect of misalignment on vibration response of coupled rotors is investigated in the present study. The coupled rotor system is modelled using Timoshenko beam elements with all six dof. An experimental approach is proposed for the first time for determination of magnitude and harmonic nature of the misalignment excitation. Misalignment effect at coupling location of rotor FE model is simulated using nodal force vector. The force vector is found using misalignment coupling stiffness matrix, derived from experimental data and applied misalignment between the two rotors. Steady-state vibration response is studied for sub-critical speeds. Effect of the types of misalignment (parallel and angular) on the vibration behaviour of the coupled rotor is examined. Along with lateral vibrations, axial and torsional vibrations are also investigated and nature of the vibration response is also examined. It has been found that the misalignment couples vibrations in bending, longitudinal and torsional modes. Some diagnostic features in the fast Fourier transform (FFT) of torsional and longitudinal response related to parallel and angular misalignment have been revealed. Full spectra and orbit plots are effectively used to reveal the unique nature of misalignment fault leading to reliable misalignment diagnostic information, not clearly brought out by earlier studies.

  19. Response to David Temperley's Commentary

    Directory of Open Access Journals (Sweden)

    William Thomson

    2006-09-01

    Full Text Available The author responds to points raised in David Temperley’s commentary, which appeared in Vol. 1, No. 2 of Empirical Musicology Review. The response includes a discussion of strengths and limitations of atemporal models of musical perception, with particular attention to presentations such as those of Carol Krumhansl and Fred Lerdahl.

  20. Mechanical Response of Thermoelectric Materials

    Energy Technology Data Exchange (ETDEWEB)

    Wereszczak, Andrew A. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Case, Eldon D. [Michigan State Univ., East Lansing, MI (United States)

    2015-05-01

    A sufficient mechanical response of thermoelectric materials (TEMats) to structural loadings is a prerequisite to the exploitation of any candidate TEMat's thermoelectric efficiency. If a TEMat is mechanically damaged or cracks from service-induced stresses, then its thermal and electrical functions can be compromised or even cease. Semiconductor TEMats tend to be quite brittle and have a high coefficient of thermal expansion; therefore, they can be quite susceptible to mechanical failure when subjected to operational thermal gradients. Because of this, sufficient mechanical response (vis-a-vis, mechanical properties) of any candidate TEMat must be achieved and sustained in the context of the service-induced stress state to which it is subjected. This report provides an overview of the mechanical responses of state-of-the-art TEMats; discusses the relevant properties that are associated with those responses and their measurement; and describes important, nonequilibrium phenomena that further complicate their use in thermoelectric devices. For reference purposes, the report also includes several appendixes that list published data on elastic properties and strengths of a variety of TEMats.