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Sample records for strong inhibitory action

  1. Inhibitory effects of sanguinarine against the cyanobacterium Microcystis aeruginosa NIES-843 and possible mechanisms of action

    Energy Technology Data Exchange (ETDEWEB)

    Shao, Jihai [College of Resources and Environment, Hunan Agricultural University, Changsha 410128 (China); Hunan Provincial Key Laboratory of Farmland Pollution Control and Agricultural Resources Use, Hunan Agricultural University, Changsha 410128 (China); Liu, Deming [State Key Laboratory Breeding Base of Crop Germplasm Innovation and Resource Utilization, Hunan Agricultural University, Changsha 410128 (China); Gong, Daoxin; Zeng, Qingru; Yan, Zhiyong [College of Resources and Environment, Hunan Agricultural University, Changsha 410128 (China); Gu, Ji-Dong, E-mail: jdgu@hku.hk [Hunan Provincial Key Laboratory of Farmland Pollution Control and Agricultural Resources Use, Hunan Agricultural University, Changsha 410128 (China); Laboratory of Environmental Microbiology and Toxicology, School of Biological Sciences, The University of Hong Kong, Hong Kong SAR (China)

    2013-10-15

    Highlights: •Sanguinarine was found as a strong algicidal biologically derived substance. •Sanguinarine can induce oxidative stress in the cells of Microcystis aeruginosa. •Photosystem is a target of toxicity of sanguinarine on M. aeruginosa. •Sanguinarine can induce DNA damage and inhibit cell division. -- Abstract: Sanguinarine showed strong inhibitory effect against Microcystis aeruginosa, a typical water bloom-forming and microcystins-producing cyanobacterium. The EC50 of sanguinarine against the growth of M. aeruginosa NIES-843 was 34.54 ± 1.17 μg/L. Results of chlorophyll fluorescence transient analysis indicated that all the electron donating side, accepting side, and the reaction center of the Photosystem II (PS II) were the targets of sanguinarine against M. aeruginosa NIES-843. The elevation of reactive oxygen species (ROS) level in the cells of M. aeruginosa NIES-843 upon exposure indicated that sanguinarine induced oxidative stress in the active growing cells of M. aeruginosa NIES-843. Further results of gene expression analysis indicated that DNA damage and cell division inhibition were also involved in the inhibitory action mechanism of sanguinarine against M. aeruginosa NIES-843. The inhibitory characteristics of sanguinarine against M. aeruginosa suggest that the ecological- and public health-risks need to be evaluated before its application in cyanobacterial bloom control to avoid devastating events irreversibly.

  2. Inhibitory noise

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    Alain Destexhe

    2010-03-01

    Full Text Available Cortical neurons in vivo may operate in high-conductance states, in which the major part of the neuron's input conductance is due to synaptic activity, sometimes several-fold larger than the resting conductance. We examine here the contribution of inhibition in such high-conductance states. At the level of the absolute conductance values, several studies have shown that cortical neurons in vivo are characterized by strong inhibitory conductances. However, conductances are balanced and spiking activity is mostly determined by fluctuations, but not much is known about excitatory and inhibitory contributions to these fluctuations. Models and dynamic-clamp experiments show that, during high-conductance states, spikes are mainly determined by fluctuations of inhibition, or by inhibitory noise. This stands in contrast to low-conductance states, in which excitatory conductances determine spiking activity. To determine these contributions from experimental data, maximum likelihood methods can be designed and applied to intracellular recordings in vivo. Such methods indicate that action potentials are indeed mostly correlated with inhibitory fluctuations in awake animals. These results argue for a determinant role for inhibitory fluctuations in evoking spikes, and do not support feed-forward modes of processing, for which opposite patterns are predicted.

  3. The Diversity of Cortical Inhibitory Synapses

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    Yoshiyuki eKubota

    2016-04-01

    Full Text Available The most typical and well known inhibitory action in the cortical microcircuit is a strong inhibition on the target neuron by axo-somatic synapses. However, it has become clear that synaptic inhibition in the cortex is much more diverse and complicated. Firstly, at least ten or more inhibitory non-pyramidal cell subtypes engage in diverse inhibitory functions to produce the elaborate activity characteristic of the different cortical states. Each distinct non-pyramidal cell subtype has its own independent inhibitory function. Secondly, the inhibitory synapses innervate different neuronal domains, such as axons, spines, dendrites and soma, and their IPSP size is not uniform. Thus cortical inhibition is highly complex, with a wide variety of anatomical and physiological modes. Moreover, the functional significance of the various inhibitory synapse innervation styles and their unique structural dynamic behaviors differ from those of excitatory synapses. In this review, we summarize our current understanding of the inhibitory mechanisms of the cortical microcircuit.

  4. Complete unconscious control: Using (in)action primes to demonstrate completely unconscious activation of inhibitory control mechanisms

    Science.gov (United States)

    Hepler, Justin; Albarracin, Dolores

    2018-01-01

    Although robust evidence indicates that action initiation can occur unconsciously and unintentionally, the literature on action inhibition suggests that inhibition requires both conscious thought and intentionality. In prior research demonstrating automatic inhibition in response to unconsciously processed stimuli, the unconscious stimuli had previously been consciously associated with an inhibitory response within the context of the experiment, and participants had consciously formed a goal to activate inhibition processes when presented with the stimuli (because task instructions required participants to engage in inhibition when the stimuli occurred). Therefore, prior work suggests that some amount of conscious thought and intentionality are required for inhibitory control. In the present research, we recorded event-related potentials during two go/no-go experiments in which participants were subliminally primed with general action/inaction concepts that had never been consciously associated with task-specific responses. We provide the first demonstration that inhibitory control processes can be modulated completely unconsciously and unintentionally. PMID:23747649

  5. Investigating a Potential Auxin-Related Mode of Hormetic/Inhibitory Action of the Phytotoxin Parthenin.

    Science.gov (United States)

    Belz, Regina G

    2016-01-01

    Parthenin is a metabolite of Parthenium hysterophorus and is believed to contribute to the weed's invasiveness via allelopathy. Despite the potential of parthenin to suppress competitors, low doses stimulate plant growth. This biphasic action was hypothesized to be auxin-like and, therefore, an auxin-related mode of parthenin action was investigated using two approaches: joint action experiments with Lactuca sativa, and dose-response experiments with auxin/antiauxin-resistant Arabidopsis thaliana genotypes. The joint action approach comprised binary mixtures of subinhibitory doses of the auxin 3-indoleacetic acid (IAA) mixed with parthenin or one of three reference compounds [indole-3-butyric acid (IBA), 2,3,5-triiodobenzoic acid (TIBA), 2-(p-chlorophenoxy)-2-methylpropionic acid (PCIB)]. The reference compounds significantly interacted with IAA at all doses, but parthenin interacted only at low doses indicating that parthenin hormesis may be auxin-related, in contrast to its inhibitory action. The genetic approach investigated the response of four auxin/antiauxin-resistant mutants and a wildtype to parthenin or two reference compounds (IAA, PCIB). The responses of mutant plants to the reference compounds confirmed previous reports, but differed from the responses observed for parthenin. Parthenin stimulated and inhibited all mutants independent of resistance. This provided no indication for an auxin-related action of parthenin. Therefore, the hypothesis of an auxin-related inhibitory action of parthenin was rejected in two independent experimental approaches, while the hypothesis of an auxin-related stimulatory effect could not be rejected.

  6. Thermal DBI action for the D3-brane at weak and strong coupling

    DEFF Research Database (Denmark)

    Grignani, Gianluca; Harmark, Troels; Marini, Andrea

    2014-01-01

    We study the effective action for finite-temperature D3-branes with an electromagnetic field at weak and strong coupling. We call this action the thermal DBI action. Comparing at low temperature the leading T4 correction for the thermal DBI action at weak and strong coupling we find that the 3/4 ...

  7. Inhibitory spectra and modes of antimicrobial action of gallotannins from mango kernels (Mangifera indica L.).

    Science.gov (United States)

    Engels, Christina; Schieber, Andreas; Gänzle, Michael G

    2011-04-01

    This study investigated the antimicrobial activities and modes of action of penta-, hexa-, hepta-, octa-, nona-, and deca-O-galloylglucose (gallotannins) isolated from mango kernels. The MICs and minimum bactericidal concentrations (MBCs) against food-borne bacteria and fungi were determined using a critical dilution assay. Gram-positive bacteria were generally more susceptible to gallotannins than were Gram-negative bacteria. The MICs of gallotannins against Bacillus subtilis, Bacillus cereus, Clostridium botulinum, Campylobacter jejuni, Listeria monocytogenes, and Staphylococcus aureus were 0.2 g liter(-1) or less; enterotoxigenic Escherichia coli and Salmonella enterica were inhibited by 0.5 to 1 g liter(-1), and lactic acid bacteria were resistant. The use of lipopolysaccharide mutants of S. enterica indicated that the outer membrane confers resistance toward gallotannins. Supplementation of LB medium with iron eliminated the inhibitory activity of gallotannins against Staphylococcus aureus, and siderophore-deficient mutants of S. enterica were less resistant toward gallotannins than was the wild-type strain. Hepta-O-galloylglucose sensitized Lactobacillus plantarum TMW1.460 to hop extract, indicating inactivation of hop resistance mechanisms, e.g., the multidrug resistance (MDR) transporter HorA. Carbohydrate metabolism of Lactococcus lactis MG1363, a conditionally respiring organism, was influenced by hepta-O-galloylglucose when grown under aerobic conditions and in the presence of heme but not under anaerobic conditions, indicating that gallotannins influence the respiratory chain. In conclusion, the inhibitory activities of gallotannins are attributable to their strong affinity for iron and likely additionally relate to the inactivation of membrane-bound proteins.

  8. A study on CYP1A inhibitory action of E-2-(4'-methoxybenzylidene)-1-benzosuberone and some related chalcones and cyclic chalcone analogues

    International Nuclear Information System (INIS)

    Monostory, Katalin; Tamasi, Viola; Vereczkey, Laszlo; Perjesi, Pal

    2003-01-01

    In vivo investigation of E-2-(4'-methoxybenzylidene)-1-benzosuberone (4a) on the 7,12-dimethylbenz[a]anthracene (DMBA)-induced onco/tumor suppressor gene expressions suggested that inhibition of metabolic activation of DMBA might play a role in the observed activity of the compound. In order to explore this possible biological action we have investigated whether 4a and some of its structurally related analogues had inhibitory effects on the CYP1A enzymes. During our study 7-ethoxyresorufin O-dealkylation activity of CYP1A isoenzymes was measured in liver microsomes prepared from 3-methylcholanthrene treated male rats. Inhibition constants (K i values) were determined by using different concentrations of 7-ethoxyresorufin and the investigated chalcones (1), E-2-benzylidene-1-indanones (2), -tetralones (3) and -benzosuberones (4). Each compound was found to be a strong competitive inhibitor of the CYP1A enzymes. Their inhibitory activity was comparable with or even higher than that of 7,8-benzoflavone, the known strong CYP1A inhibitor used as reference substance. By proper selection of the substituents on the benzylidene moiety we investigated how the inhibitory activity (K i value) of 1-4 varied as a function of the ring size (n=0, 5, 6, 7) carbon atoms, and the nature as well as the position of the substituents. To test applicability of the previously set structural requirements for binding of xenobiotics to the CYP1A enzymes we compared some topological, physico-chemical and quantum mechanical parameters of 1-4 with 7-ethoxyresorufin and 7,8-benzoflavone, the investigated CYP1A substrate and inhibitor, respectively

  9. The anticonvulsant action of the galanin receptor agonist NAX-5055 involves modulation of both excitatory- and inhibitory neurotransmission

    DEFF Research Database (Denmark)

    Walls, Anne B; Flynn, Sean P; West, Peter J

    2016-01-01

    -based anti-convulsant drugs was prompted. Based on this, a rationally designed GalR1 preferring galanin analogue, NAX-5055, was synthesized. This compound demonstrates anti-convulsant actions in several animal models of epilepsy. However, the alterations at the cellular level leading to this anti......-convulsant action of NAX-5055 are not known. Here we investigate the action of NAX-5055 at the cellular level by determining its effects on excitatory and inhibitory neurotransmission, i.e. vesicular release of glutamate and GABA, respectively, in cerebellar, neocortical and hippocampal preparations. In addition...

  10. Dual Actions of Mammalian and Piscine Gonadotropin-Inhibitory Hormones, RFamide-Related Peptides and LPXRFamide Peptides, in the Hypothalamic–Pituitary–Gonadal Axis

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    Takayoshi Ubuka

    2018-01-01

    Full Text Available Gonadotropin-inhibitory hormone (GnIH is a hypothalamic neuropeptide that decreases gonadotropin synthesis and release by directly acting on the gonadotrope or by decreasing the activity of gonadotropin-releasing hormone (GnRH neurons. GnIH is also called RFamide-related peptide in mammals or LPXRFamide peptide in fishes due to its characteristic C-terminal structure. The primary receptor for GnIH is GPR147 that inhibits cAMP production in target cells. Although most of the studies in mammals, birds, and fish have shown the inhibitory action of GnIH in the hypothalamic–pituitary–gonadal (HPG axis, several in vivo studies in mammals and many in vivo and in vitro studies in fish have shown its stimulatory action. In mouse, although the firing rate of the majority of GnRH neurons is decreased, a small population of GnRH neurons is stimulated by GnIH. In hamsters, GnIH inhibits luteinizing hormone (LH release in the breeding season when their endogenous LH level is high but stimulates LH release in non-breeding season when their LH level is basal. Besides different effects of GnIH on the HPG axis depending on the reproductive stages in fish, higher concentration or longer duration of GnIH administration can stimulate their HPG axis. These results suggest that GnIH action in the HPG axis is modulated by sex-steroid concentration, the action of neuroestrogen synthesized by the activity of aromatase stimulated by GnIH, estrogen membrane receptor, heteromerization and internalization of GnIH, GnRH, and estrogen membrane receptors. The inhibitory and stimulatory action of GnIH in the HPG axis may have a physiological role to maintain reproductive homeostasis according to developmental and reproductive stages.

  11. Inhibitory action of chlorophyllin of autosome recessive lethals induced by irradiation

    International Nuclear Information System (INIS)

    Salceda, V.M.; Pimentel, P.A.E.; Cruces, M.P.

    2006-01-01

    The chlorophyllin is a sodium salt of the chlorophyll that has a strong protective action of the damage induced by different agents so much physical as chemical. In Drosophila there is reported this effect in somatic cells. In contrast, in germinal cells using tests with the sexual chromosomes has not been found such inhibitory action. For this reason, in this occasion we will refer to the effect of the lethality induced in autosome chromosomes, in particular to the chromosome II of this species. For such effect groups of males of the line Canton-S its were pre-treated for 24h with or without 69 mm of CCS and later on treaties with or without 40 Gy of gamma irradiation. The males were then subjected to the technical Cy L / Pm for the detection of recessive lethals. In the third generation the respective counts of the descendant of each one of them to determine the corresponding categories for each extracted chromosome were made. To be mendelian crosses it is expected for a normal chromosome a proportion 2:1 of individuals with genotype Cy L / +: +/+. The absence of individuals +/+ it is indicative of a lethal gene, until 10% of these individuals of each male's total descendant, it is considered that is carrying of a semi lethal gene. The sum of lethal and semi lethals constitutes the category detrimental. The obtained results indicated that the pre-treatment with CCS reduces in a significant way the frequency of induced lethals by 40 Gy of gamma rays. The fact that an effect inhibitor has not been observed in the test of recessive lethal bound to the sex obtained previously, it contrasts with the effect observed in the chromosome II, results of this study and with the one observed in the chromosome III in somatic cells. The above-mentioned shows a differential action of the CCS between sexual chromosomes and autosomal before the effect of the gamma radiation. At the moment we don't have an explanation to these evidences. To evaluate the action of the chlorophyllin

  12. Inhibitory actions of the gamma-aminobutyric acid in pediatric Sturge-Weber syndrome.

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    Tyzio, Roman; Khalilov, Ilgam; Represa, Alfonso; Crepel, Valerie; Zilberter, Yuri; Rheims, Sylvain; Aniksztejn, Laurent; Cossart, Rosa; Nardou, Romain; Mukhtarov, Marat; Minlebaev, Marat; Epsztein, Jérôme; Milh, Mathieu; Becq, Helene; Jorquera, Isabel; Bulteau, Christine; Fohlen, Martine; Oliver, Viviana; Dulac, Olivier; Dorfmüller, Georg; Delalande, Olivier; Ben-Ari, Yehezkel; Khazipov, Roustem

    2009-08-01

    The mechanisms of epileptogenesis in Sturge-Weber syndrome (SWS) are unknown. We explored the properties of neurons from human pediatric SWS cortex in vitro and tested in particular whether gamma-aminobutyric acid (GABA) excites neurons in SWS cortex, as has been suggested for various types of epilepsies. Patch-clamp and field potential recordings and dynamic biphoton imaging were used to analyze cortical tissue samples obtained from four 6- to 14-month-old pediatric SWS patients during surgery. Neurons in SWS cortex were characterized by a relatively depolarized resting membrane potential, as was estimated from cell-attached recordings of N-methyl-D-aspartate channels. Many cells spontaneously fired action potentials at a rate proportional to the level of neuronal depolarization. The reversal potential for GABA-activated currents, assessed by cell-attached single channel recordings, was close to the resting membrane potential. All spontaneously firing neurons recorded in cell-attached mode or imaged with biphoton microscopy were inhibited by GABA. Spontaneous epileptiform activity in the form of recurrent population bursts was suppressed by glutamate receptor antagonists, the GABA(A) receptor agonist isoguvacine, and the positive allosteric GABA(A) modulator diazepam. Blockade of GABA(A) receptors aggravated spontaneous epileptiform activity. The NKCC1 antagonist bumetanide had little effect on epileptiform activity. SWS cortical neurons have a relatively depolarized resting membrane potential and spontaneously fire action potentials that may contribute to increased network excitability. In contrast to previous data depicting excitatory and proconvulsive actions of GABA in certain pediatric and adult epilepsies, GABA plays mainly an inhibitory and anticonvulsive role in SWS pediatric cortex.

  13. Inhibitory coupling between inhibitory interneurons in the spinal cord dorsal horn

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    Ribeiro-da-Silva Alfredo

    2009-05-01

    Full Text Available Abstract Local inhibitory interneurons in the dorsal horn play an important role in the control of excitability at the segmental level and thus determine how nociceptive information is relayed to higher structures. Regulation of inhibitory interneuron activity may therefore have critical consequences on pain perception. Indeed, disinhibition of dorsal horn neuronal networks disrupts the balance between excitation and inhibition and is believed to be a key mechanism underlying different forms of pain hypersensitivity and chronic pain states. In this context, studying the source and the synaptic properties of the inhibitory inputs that the inhibitory interneurons receive is important in order to predict the impact of drug action at the network level. To address this, we studied inhibitory synaptic transmission in lamina II inhibitory interneurons identified under visual guidance in spinal slices taken from transgenic mice expressing enhanced green fluorescent protein (EGFP under the control of the GAD promoter. The majority of these cells fired tonically to a long depolarizing current pulse. Monosynaptically evoked inhibitory postsynaptic currents (eIPSCs in these cells were mediated by both GABAA and glycine receptors. Consistent with this, both GABAA and glycine receptor-mediated miniature IPSCs were recorded in all of the cells. These inhibitory inputs originated at least in part from local lamina II interneurons as verified by simultaneous recordings from pairs of EGFP+ cells. These synapses appeared to have low release probability and displayed potentiation and asynchronous release upon repeated activation. In summary, we report on a previously unexamined component of the dorsal horn circuitry that likely constitutes an essential element of the fine tuning of nociception.

  14. Effective action for superfluid Fermi systems in the strong-coupling limit

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    Dupuis, N.

    2005-07-01

    We derive the low-energy effective action for three-dimensional superfluid Fermi systems in the strong-coupling limit, where superfluidity originates from Bose-Einstein condensation of composite bosons. Taking into account density and pairing fluctuations on the same footing, we show that the effective action involves only the fermion density ρr and its conjugate variable, the phase θr of the pairing order parameter Δr . We recover the standard action of a Bose superfluid of density ρr/2 , where the bosons have a mass mB=2m and interact via a repulsive contact potential with amplitude gB=4πaB/mB,aB=2a ( a the s -wave scattering length associated to the fermion-fermion interaction in vacuum). For lattice models, the derivation of the effective action is based on the mapping of the attractive Hubbard model onto the Heisenberg model in a uniform magnetic field, and a coherent state path integral representation of the partition function. The effective description of the Fermi superfluid in the strong-coupling limit is a Bose-Hubbard model with an intersite hopping amplitude tB=J/2 and an on-site repulsive interaction UB=2Jz , where J=4t2/U ( t and -U are the intersite hopping amplitude and the on-site attraction in the (fermionic) Hubbard model, z the number of nearest-neighbor sites).

  15. Effective action for superfluid Fermi systems in the strong-coupling limit

    International Nuclear Information System (INIS)

    Dupuis, N.

    2005-01-01

    We derive the low-energy effective action for three-dimensional superfluid Fermi systems in the strong-coupling limit, where superfluidity originates from Bose-Einstein condensation of composite bosons. Taking into account density and pairing fluctuations on the same footing, we show that the effective action involves only the fermion density ρ r and its conjugate variable, the phase θ r of the pairing order parameter Δ r . We recover the standard action of a Bose superfluid of density ρ r /2, where the bosons have a mass m B =2m and interact via a repulsive contact potential with amplitude g B =4πa B /m B ,a B =2a (a the s-wave scattering length associated to the fermion-fermion interaction in vacuum). For lattice models, the derivation of the effective action is based on the mapping of the attractive Hubbard model onto the Heisenberg model in a uniform magnetic field, and a coherent state path integral representation of the partition function. The effective description of the Fermi superfluid in the strong-coupling limit is a Bose-Hubbard model with an intersite hopping amplitude t B =J/2 and an on-site repulsive interaction U B =2Jz, where J=4t 2 /U (t and -U are the intersite hopping amplitude and the on-site attraction in the (fermionic) Hubbard model, z the number of nearest-neighbor sites)

  16. Investigations of organic fungicides. VIII. The biochemical mode of action of bisdithiocarbamates and diisothiocyanates

    NARCIS (Netherlands)

    Kaars Sijpesteijn, A.; Kerk, G.J.M. van der

    1954-01-01

    The inhibitory action of tetramethylene diisothiocyanate (TMDI) and of disodium ethylene bisdithiocarbamate (nabam) on the spore germination of Penicillium italicum and of Aspergillus niger is strongly antagonized by the thiol compounds, thioglycollic acid and cysteine. This antagonism is supposed

  17. The gender differences in the inhibitory action of UVB-induced melanocyte activation by the administration of tranexamic acid.

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    Hiramoto, Keiichi; Yamate, Yurika; Sugiyama, Daijiro; Takahashi, Yumi; Mafune, Eiichi

    2016-05-01

    Tranexamic acid has an inhibitory action on ultraviolet (UV) B-induced melanocyte activation. This study examined the sex differences in the inhibitory action of tranexamic acid on UVB-induced melanocyte activation. We irradiated the eye and ear of male and female mice with UVB at a dose of 1.0 kJ/m(2) using a 20SE sunlamp. We orally administered tranexamic acid (750 mg/kg/day) at 30 min before UVB exposure. Tranexamic acid inhibited the UVB-induced epidermal melanocyte activation, and the effect was more remarkable under UVB eye irradiation than under UVB ear irradiation. Furthermore, the melanocyte activity suppression effect was stronger in female mice than in male mice. Following the administration of tranexamic acid, the female displayed increased blood levels of β-endorphin and μ-opioid receptor and estradiol receptor β expression in comparison with the male. Furthermore, the effect of melanocyte activity suppression in the female mice was decreased by the administration of tamoxifen (antagonist of estrogen receptor) or naltrexone (antagonist of μ-opioid receptor). These results suggest that the suppression by tranexamic acid of the UVB-induced melanocyte activation (UVB sensitivity) is stronger in female mice than in male mice and that female hormones and β-endorphin play an important role in this sex difference. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. Evaluation of Traditional Indian Antidiabetic Medicinal Plants for Human Pancreatic Amylase Inhibitory Effect In Vitro

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    Sudha Ponnusamy

    2011-01-01

    Full Text Available Pancreatic α-amylase inhibitors offer an effective strategy to lower the levels of post prandial hyperglycemia via control of starch breakdown. Eleven Ayurvedic Indian medicinal plants with known hypoglycemic properties were subjected to sequential solvent extraction and tested for α-amylase inhibition, in order to assess and evaluate their inhibitory potential on pancreatic α-amylase. Analysis of 91 extracts, showed that 10 exhibited strong Human Pancreatic Amylase (HPA inhibitory potential. Of these, 6 extracts showed concentration dependent inhibition with IC50 values, namely, cold and hot water extracts from Ficus bengalensis bark (4.4 and 125 μgmL-1, Syzygium cumini seeds (42.1 and 4.1 μgmL-1, isopropanol extracts of Cinnamomum verum leaves (1.0 μgmL-1 and Curcuma longa rhizome (0.16 μgmL-1. The other 4 extracts exhibited concentration independent inhibition, namely, methanol extract of Bixa orellana leaves (49 μgmL-1, isopropanol extract from Murraya koenigii leaves (127 μgmL-1, acetone extracts from C. longa rhizome (7.4 μgmL-1 and Tribulus terrestris seeds (511 μgmL-1. Thus, the probable mechanism of action of the above fractions is due to their inhibitory action on HPA, thereby reducing the rate of starch hydrolysis leading to lowered glucose levels. Phytochemical analysis revealed the presence of alkaloids, proteins, tannins, cardiac glycosides, flavonoids, saponins and steroids as probable inhibitory compounds.

  19. Inhibitory effect and mode of action of chitosan solution against rice bacterial brown stripe pathogen Acidovorax avenae subsp. avenae RS-1.

    Science.gov (United States)

    Yang, Chunlan; Li, Bin; Ge, Mengyu; Zhou, Kaile; Wang, Yanli; Luo, Ju; Ibrahim, Muhammad; Xie, Guanlin; Sun, Guochang

    2014-06-04

    Inhibitory effect and mode of action of chitosan solution against rice bacterial brown stripe pathogen Acidovorax avenae subsp. avenae (Aaa) strain RS-1 was examined in this study. Result from this study indicated that chitosan solutions at 0.10, 0.20, and 0.40mg/mL inhibited the in vitro growth of Aaa strain RS-1, and in general the inhibitory efficiency increased with the increase of both chitosan concentration and the incubation time. Antibacterial activity of chitosan in this study may be mainly due to the damage of cell membrane, which was evidenced by both the cell lysis observed by transmission electron microscopy, and the increased release of cell materials based on the measurement of cell membrane integrity. Furthermore, chitosan solutions at concentrations of 0.1, 0.2, and 0.4mg/mL markedly inhibited bacterial biofilm formation compared to the control, and the inhibitory effect increased with the increase of chitosan concentration. In addition, quantitative real-time PCR of the 10 secretion system related genes revealed the differential expression of genes in particular ompA/motB, emphasizing the importance of this gene in the response of Aaa strain RS-1 to chitosan stress. These results indicated that the antibacterial mode of action of chitosan may be mainly due to membrane disruption and lysis, reduction of biofilm formation, and gene expression change. Overall, the results clearly indicated that chitosan had the potential to control bacterial brown stripe of rice. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Intrinsically-generated fluctuating activity in excitatory-inhibitory networks

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    Mastrogiuseppe, Francesca; Ostojic, Srdjan

    2017-01-01

    Recurrent networks of non-linear units display a variety of dynamical regimes depending on the structure of their synaptic connectivity. A particularly remarkable phenomenon is the appearance of strongly fluctuating, chaotic activity in networks of deterministic, but randomly connected rate units. How this type of intrinsically generated fluctuations appears in more realistic networks of spiking neurons has been a long standing question. To ease the comparison between rate and spiking networks, recent works investigated the dynamical regimes of randomly-connected rate networks with segregated excitatory and inhibitory populations, and firing rates constrained to be positive. These works derived general dynamical mean field (DMF) equations describing the fluctuating dynamics, but solved these equations only in the case of purely inhibitory networks. Using a simplified excitatory-inhibitory architecture in which DMF equations are more easily tractable, here we show that the presence of excitation qualitatively modifies the fluctuating activity compared to purely inhibitory networks. In presence of excitation, intrinsically generated fluctuations induce a strong increase in mean firing rates, a phenomenon that is much weaker in purely inhibitory networks. Excitation moreover induces two different fluctuating regimes: for moderate overall coupling, recurrent inhibition is sufficient to stabilize fluctuations; for strong coupling, firing rates are stabilized solely by the upper bound imposed on activity, even if inhibition is stronger than excitation. These results extend to more general network architectures, and to rate networks receiving noisy inputs mimicking spiking activity. Finally, we show that signatures of the second dynamical regime appear in networks of integrate-and-fire neurons. PMID:28437436

  1. An investigation into the inhibitory function of serotonin in diffuse noxious inhibitory controls in the neuropathic rat.

    Science.gov (United States)

    Bannister, K; Lockwood, S; Goncalves, L; Patel, R; Dickenson, A H

    2017-04-01

    Following neuropathy α2-adrenoceptor-mediated diffuse noxious inhibitory controls (DNIC), whereby a noxious conditioning stimulus inhibits the activity of spinal wide dynamic range (WDR) neurons, are abolished, and spinal 5-HT7 receptor densities are increased. Here, we manipulate spinal 5-HT content in spinal nerve ligated (SNL) animals and investigate which 5-HT receptor mediated actions predominate. Using in vivo electrophysiology we recorded WDR neuronal responses to von frey filaments applied to the hind paw before, and concurrent to, a noxious ear pinch (the conditioning stimulus) in isoflurane-anaesthetised rats. The expression of DNIC was quantified as a reduction in WDR neuronal firing in the presence of conditioning stimulus and was investigated in SNL rats following spinal application of (1) selective serotonin reuptake inhibitors (SSRIs) citalopram or fluoxetine, or dual application of (2) SSRI plus 5-HT7 receptor antagonist SB269970, or (3) SSRI plus α2 adrenoceptor antagonist atipamezole. DNIC were revealed in SNL animals following spinal application of SSRI, but this effect was abolished upon joint application of SSRI plus SB269970 or atipamezole. We propose that in SNL animals the inhibitory actions (quantified as the presence of DNIC) of excess spinal 5-HT (presumed present following application of SSRI) were mediated via 5-HT7 receptors. The anti-nociception depends upon an underlying tonic noradrenergic inhibitory tone via the α2-adrenoceptor. Following neuropathy enhanced spinal serotonin availability switches the predominant spinal 5-HT receptor-mediated actions but also alters noradrenergic signalling. We highlight the therapeutic complexity of SSRIs and monoamine modulators for the treatment of neuropathic pain. © 2016 European Pain Federation - EFIC®.

  2. Inhibitory Effects of Respiration Inhibitors on Aflatoxin Production

    Directory of Open Access Journals (Sweden)

    Shohei Sakuda

    2014-03-01

    Full Text Available Aflatoxin production inhibitors, which do not inhibit the growth of aflatoxigenic fungi, may be used to control aflatoxin without incurring a rapid spread of resistant strains. A respiration inhibitor that inhibits aflatoxin production was identified during a screening process for natural, aflatoxin-production inhibitors. This prompted us to evaluate respiration inhibitors as potential aflatoxin control agents. The inhibitory activities of four natural inhibitors, seven synthetic miticides, and nine synthetic fungicides were evaluated on aflatoxin production in Aspergillus parasiticus. All of the natural inhibitors (rotenone, siccanin, aptenin A5, and antimycin A inhibited fungal aflatoxin production with IC50 values around 10 µM. Among the synthetic miticides, pyridaben, fluacrypyrim, and tolfenpyrad exhibited strong inhibitory activities with IC50 values less than 0.2 µM, whereas cyflumetofen did not show significant inhibitory activity. Of the synthetic fungicides, boscalid, pyribencarb, azoxystrobin, pyraclostrobin, and kresoxim-methyl demonstrated strong inhibitory activities, with IC50 values less than 0.5 µM. Fungal growth was not significantly affected by any of the inhibitors tested at concentrations used. There was no correlation observed between the targets of respiration inhibitors (complexes I, II, and III and their IC50 values for aflatoxin-production inhibitory activity. This study suggests that respiration inhibitors, including commonly used pesticides, are useful for aflatoxin control.

  3. Inhibitory Effects of Respiration Inhibitors on Aflatoxin Production

    Science.gov (United States)

    Sakuda, Shohei; Prabowo, Diyan Febri; Takagi, Keiko; Shiomi, Kazuro; Mori, Mihoko; Ōmura, Satoshi; Nagasawa, Hiromichi

    2014-01-01

    Aflatoxin production inhibitors, which do not inhibit the growth of aflatoxigenic fungi, may be used to control aflatoxin without incurring a rapid spread of resistant strains. A respiration inhibitor that inhibits aflatoxin production was identified during a screening process for natural, aflatoxin-production inhibitors. This prompted us to evaluate respiration inhibitors as potential aflatoxin control agents. The inhibitory activities of four natural inhibitors, seven synthetic miticides, and nine synthetic fungicides were evaluated on aflatoxin production in Aspergillus parasiticus. All of the natural inhibitors (rotenone, siccanin, aptenin A5, and antimycin A) inhibited fungal aflatoxin production with IC50 values around 10 µM. Among the synthetic miticides, pyridaben, fluacrypyrim, and tolfenpyrad exhibited strong inhibitory activities with IC50 values less than 0.2 µM, whereas cyflumetofen did not show significant inhibitory activity. Of the synthetic fungicides, boscalid, pyribencarb, azoxystrobin, pyraclostrobin, and kresoxim-methyl demonstrated strong inhibitory activities, with IC50 values less than 0.5 µM. Fungal growth was not significantly affected by any of the inhibitors tested at concentrations used. There was no correlation observed between the targets of respiration inhibitors (complexes I, II, and III) and their IC50 values for aflatoxin-production inhibitory activity. This study suggests that respiration inhibitors, including commonly used pesticides, are useful for aflatoxin control. PMID:24674936

  4. Voluntary inhibitory motor control over involuntary tic movements.

    Science.gov (United States)

    Ganos, Christos; Rothwell, John; Haggard, Patrick

    2018-03-06

    Inhibitory control is crucial for normal adaptive motor behavior. In hyperkinesias, such as tics, disinhibition within the cortico-striato-thalamo-cortical loops is thought to underlie the presence of involuntary movements. Paradoxically, tics are also subject to voluntary inhibitory control. This puzzling clinical observation questions the traditional definition of tics as purely involuntary motor behaviors. Importantly, it suggests novel insights into tic pathophysiology. In this review, we first define voluntary inhibitory tic control and compare it with other notions of tic control from the literature. We then examine the association between voluntary inhibitory tic control with premonitory urges and review evidence linking voluntary tic inhibition to other forms of executive control of action. We discuss the somatotopic selectivity and the neural correlates of voluntary inhibitory tic control. Finally, we provide a scientific framework with regard to the clinical relevance of the study of voluntary inhibitory tic control within the context of the neurodevelopmental disorder of Tourette syndrome. We identify current knowledge gaps that deserve attention in future research. © 2018 International Parkinson and Movement Disorder Society. © 2018 International Parkinson and Movement Disorder Society.

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

    Science.gov (United States)

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

    1996-09-02

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

  6. The neuropsychopharmacology of action inhibition: cross-species translation of the stop-signal and go/no-go tasks.

    Science.gov (United States)

    Eagle, Dawn M; Bari, Andrea; Robbins, Trevor W

    2008-08-01

    The term 'action inhibition' encapsulates the ability to prevent any form of planned physical response. Growing evidence suggests that different 'stages' or even subtypes of action inhibition activate subtly different neuropharmacological and neuroanatomical processes. In this review, we present evidence from two commonly used and apparently similar behavioural tests, the stop-signal task and the go/no-go task, to determine if these have similar neuroanatomical and neurochemical modulation. Whilst performance of the stop-signal and go/no-go tasks is modulated across only subtly different anatomical networks, serotonin (5-HT) is strongly implicated in inhibitory control on the go/no-go but not the stop-signal task, whereas the stop-signal reaction time appears more sensitive to the action of noradrenaline. There is clear neuropharmacological and neuroanatomical evidence that stop-signal and go/no-go tasks represent different forms of action inhibition. This evidence translates with remarkable consistency across species. We discuss the possible implications of this evidence with respect to the development of novel therapeutic treatments for disorders in which inhibitory deficits are prominent and debilitating.

  7. Alpha-Glucosidase Inhibitory and Antioxidant Activity of Solvent ...

    African Journals Online (AJOL)

    regression analysis. Phytochemical contents and correlation with bioactivities. Total phenolic (TP), total proanthocyanidin. (TPro), and total hydroxycinnamic acid ..... An advantage of competitive inhibitors is that their inhibitory action is reversible, thus allowing undesirable effects to be readily mitigated by decreasing the ...

  8. Phenotypic characterisation and assessment of the inhibitory ...

    African Journals Online (AJOL)

    Six strains of Lactobacillus spp. were isolated from fermenting corn slurry, fresh cow milk, and the faeces of pig, albino rat, and human infant. Their inhibitory action was tested against some spoilage and pathogenic bacteria. Lactobacillus acidophilus isolated from milk was found to display a higher antagonistic effect with ...

  9. Mechanical effects of strong measurement: back-action noise and cooling

    Science.gov (United States)

    Schwab, Keith

    2007-03-01

    Our recent experiments show that it is now possible to prepare and measure mechanical systems with thermal occupation factors of N˜25 and perform continuous position measurements close to the limits required by the Heisenberg Uncertainty Principle (1). I will discuss our back-action measurements with nanomechanical structures strongly coupled to single electron transistors. We have been able to observe the stochastic back-action forces exerted by the SET as well as a cooling effect which has analogies to cooling in optical cavities. Furthermore, I will discuss progress using optical fields coupled to mechanical modes which show substantial cooling using the pondermotive effects of the photons impacting a flexible dielectric mirror (2). Both of these techniques pave the way to demonstrating the true quantum properties of a mechanical device: squeezed states, superposition states, and entangled states. (1) ``Quantum Measurement Backaction and Cooling Observed with a Nanomechanical Resonator,'' A. Naik, O. Buu, M.D. LaHaye, M.P. Blencowe, A.D. Armour, A.A. Clerk, K.C. Schwab, Nature 443, 193 (2006). (2) ``Self-cooling of a micro-mirror by radiation pressure,'' S. Gigan, H.R. Boehm, M. Patemostro, F. Blaser, G. Langer, J. Hertzberg, K. Schwab, D. Baeuerle, M. Aspelmeyer, A. Zeilinger, Nature 444, 67 (2006).

  10. Self-reported impulsivity and inhibitory control in problem gamblers.

    Science.gov (United States)

    Lorains, Felicity K; Stout, Julie C; Bradshaw, John L; Dowling, Nicki A; Enticott, Peter G

    2014-01-01

    Impulsivity is considered a core feature of problem gambling; however, self-reported impulsivity and inhibitory control may reflect disparate constructs. We examined self-reported impulsivity and inhibitory control in 39 treatment-seeking problem gamblers and 41 matched controls using a range of self-report questionnaires and laboratory inhibitory control tasks. We also investigated differences between treatment-seeking problem gamblers who prefer strategic (e.g., sports betting) and nonstrategic (e.g., electronic gaming machines) gambling activities. Treatment-seeking problem gamblers demonstrated elevated self-reported impulsivity, more go errors on the Stop Signal Task, and a lower gap score on the Random Number Generation task than matched controls. However, overall we did not find strong evidence that treatment-seeking problem gamblers are more impulsive on laboratory inhibitory control measures. Furthermore, strategic and nonstrategic problem gamblers did not differ from their respective controls on either self-reported impulsivity questionnaires or laboratory inhibitory control measures. Contrary to expectations, our results suggest that inhibitory dyscontrol may not be a key component for some treatment-seeking problem gamblers.

  11. [Mechanism of the inhibitory action of allelochemical dibutyl phthalate on algae Gymnodinium breve].

    Science.gov (United States)

    Bie, Cong-Cong; Li, Feng-Min; Wang, Yi-Fei; Wang, Hao-Yun; Zhao, Ya-Han; Zhao, Wei; Wang, Zhen-Yu

    2012-01-01

    The aim of this study was to investigate the mechanism of inhibitory action of dibutyl phthalate (DBP) on red tide algae Gymnodinium breve. The effects of DBP on malonaldehyde, subcellular structure and superoxide dismutase (SOD) isoforms were investigated. The results showed that MDA accumulated in the algae cell under DBP exposure, and for the 3 mg x L(-1) DBP treated algae culture a peak value of 0.34 micromol x (10(9) cells) (-1) occurred at 72 h, which was about 2. 3 times than that of the control. TEM pictures showed the disruption of DBP on the subcellular structure of G. breve. A morphological phenomenon appeared that the algae cell was commonly found small tubules or apical parts around the cell membrane, and almost all normal cell organelles were indistinguishable finally. The activity of CuZn-SOD (main cytoplast located isoform with little in cloroplast) under DBP exposure was higher than that of the control, and no significant difference was observed on Fe-SOD (chloroplast located isoform) activity, but for the Mn-SOD (mitochondrial isoform), the activity was significantly inhibited. These results indicated that DBP might inhibit the algae growth from the plasma membrane and the mitochondria, resulting in oxidative damage in algae cell and a final death. This paper will give a theoretical support to the practical usage of the allelochemical on red tide algae.

  12. Purification, identification and molecular mechanism of two dipeptidyl peptidase IV (DPP-IV) inhibitory peptides from Antarctic krill (Euphausia superba) protein hydrolysate.

    Science.gov (United States)

    Ji, Wei; Zhang, Chaohua; Ji, Hongwu

    2017-10-01

    Dipeptidyl peptidase IV (DPP-IV) played an important role in blood glucose regulation. Inhibition of DPP-IV may improve glycemic control in diabetics by preventing the rapid breakdown of incretin hormones and prolonging their physiological action. In this study, Antarctic krill (Euphausia superba) protein was hydrolyzed using animal proteolytic enzymes. The hydrolysate was purified sequentially by ultrafiltration, gel filtration chromatography and reversed phase high-performance liquid chromatography (RP-HPLC). DPP-IV inhibitory activity of the fractions achieved from Antarctic krill protein was determined by DPP-IV screening reagent kit. Two purified peptides were identified by Xevo G2-XS QTof mass spectrometer (QTOF-MS). One peptide purified was Ala-Pro (AP) with IC 50 values of 0.0530mg/mL, the other Ile-Pro-Ala (IPA) with IC 50 values of 0.0370mg/mL. They both exhibited strong DPP-IV inhibitory activity. The molecular docking analysis revealed that DPP-IV inhibition by AP and IPA was mainly due to formation of a strong interaction surface force with the 91-96 and 101-105 amino acids of the DPP-IV. Our results suggested that the protein hydrolysate from Antarctic krill can be considered as a promising natural source of DPP-IV inhibitory peptides in the management of diabetes. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Growth inhibition of Listeria spp. on Camembert cheese by bacteria producing inhibitory substances.

    Science.gov (United States)

    Sulzer, G; Busse, M

    1991-12-01

    Bacterial strains exhibiting antimicrobial activity towards other bacteria are quite common in nature. During the past few years several genera have been shown to exert inhibitory action against Listeria. spp. In the present work strains of Enterococcus, Lactobacillus and Lactococcus were tested for their influence on the development of Listeria spp. on Camembert cheese. Partial or complete inhibition of growth of Listeria spp. was observed using various inhibitory bacteria. Complete inhibition occurred when the inhibitory strain was used as a starter culture and there was a low level of contamination with Listeria spp. during the first stage of ripening. Very little inhibition occurred if the inhibitory strain was added together with the starter culture.

  14. Macrolides decrease the minimal inhibitory concentration of anti-pseudomonal agents against Pseudomonas aeruginosa from cystic fibrosis patients in biofilm

    Directory of Open Access Journals (Sweden)

    Lutz Larissa

    2012-09-01

    Full Text Available Abstract Background Biofilm production is an important mechanism for bacterial survival and its association with antimicrobial resistance represents a challenge for the patient treatment. In this study we evaluated the in vitro action of macrolides in combination with anti-pseudomonal agents on biofilm-grown Pseudomonas aeruginosa recovered from cystic fibrosis (CF patients. Results A total of 64 isolates were analysed. The biofilm inhibitory concentration (BIC results were consistently higher than those obtained by the conventional method, minimal inhibitory concentration, (MIC for most anti-pseudomonal agents tested (ceftazidime: P = 0.001, tobramycin: P = 0.001, imipenem: P P = 0.005. When macrolides were associated with the anti-pseudomonal agents, the BIC values were reduced significantly for ceftazidime (P  0.001 and tobramycin (P  0.001, regardless the concentration of macrolides. Strong inhibitory quotient was observed when azithromycin at 8 mg/L was associated with all anti-pseudomonal agents tested in biofilm conditions. Conclusions P. aeruginosa from CF patients within biofilms are highly resistant to antibiotics but macrolides proved to augment the in vitro activity of anti-pseudomonal agents.

  15. Action inhibition in Tourette syndrome.

    Science.gov (United States)

    Ganos, Christos; Kühn, Simone; Kahl, Ursula; Schunke, Odette; Feldheim, Jan; Gerloff, Christian; Roessner, Veit; Bäumer, Tobias; Thomalla, Götz; Haggard, Patrick; Münchau, Alexander

    2014-10-01

    Tourette syndrome is a neuropsychiatric disorder characterized by tics. Tic generation is often linked to dysfunction of inhibitory brain networks. Some previous behavioral studies found deficiencies in inhibitory motor control in Tourette syndrome, but others suggested normal or even better-than-normal performance. Furthermore, neural correlates of action inhibition in these patients are poorly understood. We performed event-related functional magnetic resonance imaging during a stop-signal reaction-time task in 14 uncomplicated adult Tourette patients and 15 healthy controls. In patients, we correlated activations in stop-signal reaction-time task with their individual motor tic frequency. Task performance was similar in both groups. Activation of dorsal premotor cortex was stronger in the StopSuccess than in the Go condition in healthy controls. This pattern was reversed in Tourette patients. A significant positive correlation was present between motor tic frequency and activations in the supplementary motor area during StopSuccess versus Go in patients. Inhibitory brain networks differ between healthy controls and Tourette patients. In the latter the supplementary motor area is probably a key relay of inhibitory processes mediating both suppression of tics and inhibition of voluntary action. © 2014 International Parkinson and Movement Disorder Society.

  16. A Group Action Method for Construction of Strong Substitution Box

    Science.gov (United States)

    Jamal, Sajjad Shaukat; Shah, Tariq; Attaullah, Atta

    2017-06-01

    In this paper, the method to develop cryptographically strong substitution box is presented which can be used in multimedia security and data hiding techniques. The algorithm of construction depends on the action of a projective general linear group over the set of units of the finite commutative ring. The strength of substitution box and ability to create confusion is assessed with different available analyses. Moreover, the ability of resistance against malicious attacks is also evaluated. The substitution box is examined by bit independent criterion, strict avalanche criterion, nonlinearity test, linear approximation probability test and differential approximation probability test. This substitution box is equated with well-recognized substitution boxes such as AES, Gray, APA, S8, prime of residue, Xyi and Skipjack. The comparison shows encouraging results about the strength of the proposed box. The majority logic criterion is also calculated to analyze the strength and its practical implementation.

  17. Cortical Interneuron Subtypes Vary in Their Axonal Action Potential Properties.

    Science.gov (United States)

    Casale, Amanda E; Foust, Amanda J; Bal, Thierry; McCormick, David A

    2015-11-25

    The role of interneurons in cortical microcircuits is strongly influenced by their passive and active electrical properties. Although different types of interneurons exhibit unique electrophysiological properties recorded at the soma, it is not yet clear whether these differences are also manifested in other neuronal compartments. To address this question, we have used voltage-sensitive dye to image the propagation of action potentials into the fine collaterals of axons and dendrites in two of the largest cortical interneuron subtypes in the mouse: fast-spiking interneurons, which are typically basket or chandelier neurons; and somatostatin containing interneurons, which are typically regular spiking Martinotti cells. We found that fast-spiking and somatostatin-expressing interneurons differed in their electrophysiological characteristics along their entire dendrosomatoaxonal extent. The action potentials generated in the somata and axons, including axon collaterals, of somatostatin-expressing interneurons are significantly broader than those generated in the same compartments of fast-spiking inhibitory interneurons. In addition, action potentials back-propagated into the dendrites of somatostatin-expressing interneurons much more readily than fast-spiking interneurons. Pharmacological investigations suggested that axonal action potential repolarization in both cell types depends critically upon Kv1 channels, whereas the axonal and somatic action potentials of somatostatin-expressing interneurons also depend on BK Ca(2+)-activated K(+) channels. These results indicate that the two broad classes of interneurons studied here have expressly different subcellular physiological properties, allowing them to perform unique computational roles in cortical circuit operations. Neurons in the cerebral cortex are of two major types: excitatory and inhibitory. The proper balance of excitation and inhibition in the brain is critical for its operation. Neurons contain three main

  18. Assessment of the inhibitory effects of pyrethroids against human carboxylesterases

    Energy Technology Data Exchange (ETDEWEB)

    Lei, Wei [The Second Affiliated Hospital of Dalian Medical University, Dalian 110623 (China); Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023 (China); Wang, Dan-Dan; Dou, Tong-Yi [Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023 (China); Hou, Jie [Dalian Medical University, Dalian 116044 (China); Feng, Liang; Yin, Heng [Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023 (China); Luo, Qun [Beijing National Laboratory for Molecular Science, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100080 (China); Sun, Jie [The Second Affiliated Hospital of Dalian Medical University, Dalian 110623 (China); Ge, Guang-Bo, E-mail: geguangbo@dicp.ac.cn [Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023 (China); Yang, Ling [Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023 (China)

    2017-04-15

    Pyrethroids are broad-spectrum insecticides that widely used in many countries, while humans may be exposed to these toxins by drinking or eating pesticide-contaminated foods. This study aimed to investigate the inhibitory effects of six commonly used pyrethroids against two major human carboxylesterases (CES) including CES1 and CES2. Three optical probe substrates for CES1 (DME, BMBT and DMCB) and a fluorescent probe substrate for CES2 (DDAB) were used to characterize the inhibitory effects of these pyrethroids. The results demonstrated that most of the tested pyrethroids showed moderate to weak inhibitory effects against both CES1 and CES2, but deltamethrin displayed strong inhibition towards CES1. The IC{sub 50} values of deltamethrin against CES1-mediated BMBT, DME, and DMCB hydrolysis were determined as 1.58 μM, 2.39 μM, and 3.3 μM, respectively. Moreover, deltamethrin was cell membrane permeable and capable of inhibition endogenous CES1 in living cells. Further investigation revealed that deltamethrin inhibited CES1-mediated BMBT hydrolysis via competitive manner but noncompetitively inhibited DME or DMCB hydrolysis. The inhibition behaviors of deltamethrin against CES1 were also studied by molecular docking simulation. The results demonstrated that CES1 had at least two different ligand-binding sites, one was the DME site and another was the BMBT site which was identical to the binding site of deltamethrin. In summary, deltamethrin was a strong reversible inhibitor against CES1 and it could tightly bind on CES1 at the same ligand-binding site as BMBT. These findings are helpful for the deep understanding of the interactions between xenobiotics and CES1. - Highlights: • The inhibitory effects of six commonly used pyrethroids on human carboxylesterases were investigated. • Deltamethrin displayed strong inhibitory effects against human carboxylesterase 1 (CES1). • Deltamethrin was cell membrane permeable and could inhibit intracellular CES1 in living

  19. Assessment of the inhibitory effects of pyrethroids against human carboxylesterases

    International Nuclear Information System (INIS)

    Lei, Wei; Wang, Dan-Dan; Dou, Tong-Yi; Hou, Jie; Feng, Liang; Yin, Heng; Luo, Qun; Sun, Jie; Ge, Guang-Bo; Yang, Ling

    2017-01-01

    Pyrethroids are broad-spectrum insecticides that widely used in many countries, while humans may be exposed to these toxins by drinking or eating pesticide-contaminated foods. This study aimed to investigate the inhibitory effects of six commonly used pyrethroids against two major human carboxylesterases (CES) including CES1 and CES2. Three optical probe substrates for CES1 (DME, BMBT and DMCB) and a fluorescent probe substrate for CES2 (DDAB) were used to characterize the inhibitory effects of these pyrethroids. The results demonstrated that most of the tested pyrethroids showed moderate to weak inhibitory effects against both CES1 and CES2, but deltamethrin displayed strong inhibition towards CES1. The IC 50 values of deltamethrin against CES1-mediated BMBT, DME, and DMCB hydrolysis were determined as 1.58 μM, 2.39 μM, and 3.3 μM, respectively. Moreover, deltamethrin was cell membrane permeable and capable of inhibition endogenous CES1 in living cells. Further investigation revealed that deltamethrin inhibited CES1-mediated BMBT hydrolysis via competitive manner but noncompetitively inhibited DME or DMCB hydrolysis. The inhibition behaviors of deltamethrin against CES1 were also studied by molecular docking simulation. The results demonstrated that CES1 had at least two different ligand-binding sites, one was the DME site and another was the BMBT site which was identical to the binding site of deltamethrin. In summary, deltamethrin was a strong reversible inhibitor against CES1 and it could tightly bind on CES1 at the same ligand-binding site as BMBT. These findings are helpful for the deep understanding of the interactions between xenobiotics and CES1. - Highlights: • The inhibitory effects of six commonly used pyrethroids on human carboxylesterases were investigated. • Deltamethrin displayed strong inhibitory effects against human carboxylesterase 1 (CES1). • Deltamethrin was cell membrane permeable and could inhibit intracellular CES1 in living cells

  20. Isolation of proanthocyanidins from red wine, and their inhibitory effects on melanin synthesis in vitro.

    Science.gov (United States)

    Fujimaki, Takahiro; Mori, Shoko; Horikawa, Manabu; Fukui, Yuko

    2018-05-15

    The red wines made from Vitis vinifera were identified as skin-whitening effectors by using in vitro assays. OPCs in the wine were evaluated for tyrosinase activity and melanogenesis. Strong tyrosinase inhibitory activity was observed in fractions with high oligomeric proanthocyanidin (OPC) content. Among OPC dimers, a strong inhibitory effect on tyrosinase was observed with OPCs which contain (+)-catechin as an upper unit. Melanogenesis inhibitory effect was observed with OPCs which have (-)-epicatechin as upper units. Also, OPC trimers, upper and middle units joined with 4 → 8 bonds, showed stronger effects compared to trimers with 4 → 6 linkages. Interestingly, (-)-epicatechin-(4β → 8)-(-)-epicatechin 3-O-gallate, which is a unique component of grapes has potent inhibitory effects on both tyrosinase and melanogenesis. Our data provide structural information about such active compounds. These results suggest that red wines containing OPC, have high melanogenesis inhibitory effect and are supposed to have skin-whitening effect. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Fear extinction causes target-specific remodeling of perisomatic inhibitory synapses

    Science.gov (United States)

    Trouche, Stéphanie; Sasaki, Jennifer M.; Tu, Tiffany; Reijmers, Leon G.

    2013-01-01

    SUMMARY A more complete understanding of how fear extinction alters neuronal activity and connectivity within fear circuits may aid in the development of strategies to treat human fear disorders. Using a c-fos based transgenic mouse, we found that contextual fear extinction silenced basal amygdala (BA) excitatory neurons that had been previously activated during fear conditioning. We hypothesized that the silencing of BA fear neurons was caused by an action of extinction on BA inhibitory synapses. In support of this hypothesis, we found extinction-induced target-specific remodeling of BA perisomatic inhibitory synapses originating from parvalbumin and cholecystokinin-positive interneurons. Interestingly, the predicted changes in the balance of perisomatic inhibition matched the silent and active states of the target BA fear neurons. These observations suggest that target-specific changes in perisomatic inhibitory synapses represent a mechanism through which experience can sculpt the activation patterns within a neural circuit. PMID:24183705

  2. Inhibitory Effects of Standardized Extracts of Phyllanthus amarus and Phyllanthus urinaria and Their Marker Compounds on Phagocytic Activity of Human Neutrophils

    Directory of Open Access Journals (Sweden)

    Yuandani

    2013-01-01

    Full Text Available The standardized methanol extracts of Phyllanthus amarus and P. urinaria, collected from Malaysia and Indonesia, and their isolated chemical markers, phyllanthin and hypophyllanthin, were evaluated for their effects on the chemotaxis, phagocytosis and chemiluminescence of human phagocytes. All the plant extracts strongly inhibited the migration of polymorphonuclear leukocytes (PMNs with the Malaysian P. amarus showing the strongest inhibitory activity (IC50 value, 1.1 µg/mL. There was moderate inhibition by the extracts of the bacteria engulfment by the phagocytes with the Malaysian P. amarus exhibiting the highest inhibition (50.8% of phagocytizing cells. The Malaysian P. amarus and P. urinaria showed strong reactive oxygen species (ROS inhibitory activity, with both extracts exhibiting IC50 value of 0.7 µg/mL. Phyllanthin and hypophyllanthin exhibited relatively strong activity against PMNs chemotaxis, with IC50 values slightly lower than that of ibuprofen (1.4 µg/mL. Phyllanthin exhibited strong inhibitory activity on the oxidative burst with an IC50 value comparable to that of aspirin (1.9 µg/mL. Phyllanthin exhibited strong engulfment inhibitory activity with percentage of phagocytizing cells of 14.2 and 27.1% for neutrophils and monocytes, respectively. The strong inhibitory activity of the extracts was due to the presence of high amounts of phyllanthin and hypophyllanthin although other constituents may also contribute.

  3. Degree of synchronization modulated by inhibitory neurons in clustered excitatory-inhibitory recurrent networks

    Science.gov (United States)

    Li, Huiyan; Sun, Xiaojuan; Xiao, Jinghua

    2018-01-01

    An excitatory-inhibitory recurrent neuronal network is established to numerically study the effect of inhibitory neurons on the synchronization degree of neuronal systems. The obtained results show that, with the number of inhibitory neurons and the coupling strength from an inhibitory neuron to an excitatory neuron increasing, inhibitory neurons can not only reduce the synchronization degree when the synchronization degree of the excitatory population is initially higher, but also enhance it when it is initially lower. Meanwhile, inhibitory neurons could also help the neuronal networks to maintain moderate synchronized states. In this paper, we call this effect as modulation effect of inhibitory neurons. With the obtained results, it is further revealed that the ratio of excitatory neurons to inhibitory neurons being nearly 4 : 1 is an economic and affordable choice for inhibitory neurons to realize this modulation effect.

  4. Impaired inhibition of prepotent motor actions in patients with Tourette syndrome.

    Science.gov (United States)

    Wylie, Scott A; Claassen, Daniel O; Kanoff, Kristen E; Ridderinkhof, K Richard; van den Wildenberg, Wery P M

    2013-09-01

    Evidence that tic behaviour in individuals with Tourette syndrome reflects difficulties inhibiting prepotent motor actions is mixed. Response conflict tasks produce sensitive measures of response interference from prepotent motor impulses and the proficiency of inhibiting these impulses as an act of cognitive control. We tested the hypothesis that individuals with Tourette syndrome show a deficit in inhibiting prepotent motor actions. Healthy controls and older adolescents/adults with persistent Tourette syndrome without a history of obsessive-compulsive disorder or attention-deficit/hyperactivity disorder and presenting with stable mood functioning (i.e., no history of well-treated anxiety or depression) participated in this study. They performed a Simon task that induced conflict between prepotent actions and goal-directed actions. A novel theoretical framework distinguished group differences in acting impulsively (i.e., fast motor errors) from the proficiency of inhibiting interference by prepotent actions (i.e., slope of interference reduction). We included 27 controls and 28 individuals with Tourette syndrome in our study. Both groups showed similar susceptibility to making fast, impulsive motor errors (Tourette syndrome 26% v. control 23%; p = 0.10). The slope (m) reduction of the interference effect was significantly less pronounced among participants with Tourette syndrome than controls (Tourette syndrome: m = -0.07 v. control: m = -0.23; p = 0.022), consistent with deficient inhibitory control over prepotent actions in Tourette syndrome. This study does not address directly the role of psychiatric comorbidities and medication effects on inhibitory control over impulsive actions in individuals with Tourette syndrome. The results offer empirical evidence for deficient inhibitory control over prepotent motor actions in individuals with persistent Tourette syndrome with minimal to absent psychiatric comorbidities. These findings also suggest that the frontal

  5. <strong>Entrepreneurial Action in Shaping Education for Entrepreneurshipstrong>

    DEFF Research Database (Denmark)

    Christensen, Poul Rind; Kirketerp Linstad, Anne

    entrepreneurship training and education. Neutral assessments of the school have indicated that more than 50 percent of the students graduated from the school has started their own business and furthermore that the students exercise a strong entrepreneurial behaviour (Deichman-Sørensen 1997). Seemingly the school...... also started to pay attention to the apparent success of the KaosPilots. What is the secret of their recipe? In this contribution we want to explore how the KaosPilots form their pedagogical concepts of teaching entrepreneurship and enterprise behaviour....

  6. Dogs' reaction to inequity is affected by inhibitory control.

    Science.gov (United States)

    Brucks, Désirée; Range, Friederike; Marshall-Pescini, Sarah

    2017-11-17

    Inequity aversion is thought to act as a mechanism to ensure cooperation and has been studied in many different species, consistently revealing inter-individual variation. Inhibitory control has been proposed to act as one factor responsible for this variation since individuals need to inhibit performing the required action and/or refuse rewards in order to exhibit inequity aversion. Here, we investigated if dogs' sensitivity to inequity is affected by their capacity for inhibitory control, assessed in a test battery and questionnaire. Overall, dogs showing high compulsivity scores (i.e. repetitive behaviours independent of feedback) were more motivated to participate in the inequity task independent of the rewarding scheme. Dogs were more sensitive to inequity and individual contrast if they exhibited a slower decision speed in the inhibition tasks. Furthermore, less persistent and more impulsive dogs were more sensitive to reward inequity, potentially due to having a lower tolerance level for frustration. Results indicate that aspects of inhibitory control can explain the variation in dogs' inequity response, highlighting one of the mechanisms underlying responses to inequity. Emphasising the importance to design paradigms, which allow us to disentangle capacities to recognise inequity from the inability to react to it due to poor inhibitory control abilities.

  7. In vitro anti-Helicobacter pylori action of 30 Chinese herbal medicines used to treat ulcer diseases.

    Science.gov (United States)

    Li, Yang; Xu, Chen; Zhang, Qiang; Liu, Jun Yan; Tan, Ren Xiang

    2005-04-26

    Infection by Helicobacter pylori has been ascertained to be an important etiologic impetus leading usually to chronic active gastritis and gastric ulcer with growing incidences worldwide. Utilizing as the test pathogen a standard and five clinic strains of Helicobacter pylori, the antibacterial action was assessed in vitro with ethanol extracts of 30 Chinese herbal medicines which have been frequently prescribed since ancient times for treating gastritis-like disorders. Among the 30 tested materials, the ethanol extracts of Abrus cantoniensis (Fabaceae), Saussurea lappa (Asteraceae) and Eugenia caryophyllata (Myrtaceae) were strongly inhibitory to all test strains (MICs: approximately 40 microg/ml), and Hippophae rhamnoides (Elaeagnaceae), Fritillaria thunbergii (Liliaceae), Magnolia officinalis and Schisandra chinensis (Magnoliaceae), Corydalis yanhusuo (Papaveraceae), Citrus reticulata (Rutaceae), Bupleurum chinense and Ligusticum chuanxiong (Apiaceae) substantially active with MICs close to 60.0 microg/ml. As to antibacterial actions of the aqueous extracts of the same drugs, those derived from Cassia obtusifolia (Fabaceae), Fritillaria thunbergii and Eugenia caryophyllata were remarkably inhibitory against all the six Helicobacter pylori strains (MICs: approximately 60 microg/ml). The work compared almost quantitatively the magnitude of the anti-Helicobacter pylori actions of the 30 most prescribed gastritis-treating Chinese herbal drugs, and located as well some source plants where potent anti-Helicobacter pylori phytochemicals could be characterized.

  8. Fear extinction causes target-specific remodeling of perisomatic inhibitory synapses.

    Science.gov (United States)

    Trouche, Stéphanie; Sasaki, Jennifer M; Tu, Tiffany; Reijmers, Leon G

    2013-11-20

    A more complete understanding of how fear extinction alters neuronal activity and connectivity within fear circuits may aid in the development of strategies to treat human fear disorders. Using a c-fos-based transgenic mouse, we found that contextual fear extinction silenced basal amygdala (BA) excitatory neurons that had been previously activated during fear conditioning. We hypothesized that the silencing of BA fear neurons was caused by an action of extinction on BA inhibitory synapses. In support of this hypothesis, we found extinction-induced target-specific remodeling of BA perisomatic inhibitory synapses originating from parvalbumin and cholecystokinin-positive interneurons. Interestingly, the predicted changes in the balance of perisomatic inhibition matched the silent and active states of the target BA fear neurons. These observations suggest that target-specific changes in perisomatic inhibitory synapses represent a mechanism through which experience can sculpt the activation patterns within a neural circuit. Copyright © 2013 Elsevier Inc. All rights reserved.

  9. NMDAR-mediated calcium transients elicited by glutamate co-release at developing inhibitory synapses

    Directory of Open Access Journals (Sweden)

    Abigail Kalmbach

    2010-07-01

    Full Text Available Before hearing onset, the topographic organization of the inhibitory sound localization pathway from the medial nucleus of the trapezoid body (MNTB to the lateral superior olive (LSO is refined by means of synaptic silencing and strengthening. During this refinement period MNTB-LSO synapses not only release GABA and glycine but also release glutamate. This co-released glutamate can elicit postsynaptic currents that are predominantly mediated by NMDA receptors (NMDARs. To gain a better understanding of how glutamate contributes to synaptic signaling at developing MNTB-LSO inhibitory synapse, we investigated to what degree and under what conditions NMDARs contribute to postsynaptic calcium responses. Our results demonstrate that MNTB-LSO synapses can elicit compartmentalized calcium responses along aspiny LSO dendrites. These responses are significantly attenuated by the NMDARs antagonist APV. APV, however, has no effect on somatically recorded electrical postsynaptic responses, indicating little, if any, contribution of NMDARs to spike generation. Small NMDAR-mediated calcium responses were also observed under physiological levels of extracellular magnesium concentrations indicating that MNTB-LSO synapses activate magnesium sensitive NMDAR on immature LSO dendrites. In Fura-2 AM loaded neurons, blocking GABAA and glycine receptors decreased NMDAR contribution to somatic calcium responses suggesting that GABA and glycine, perhaps by shunting backpropagating action potentials, decrease the level of NMDAR activation under strong stimulus conditions.

  10. The persistent inhibitory properties of saxagliptin on renal dipeptidyl peptidase-4: Studies with HK-2 cells in vitro and normal rats in vivo

    Directory of Open Access Journals (Sweden)

    Masako Uchii

    2017-11-01

    Full Text Available Saxagliptin, a potent and selective DPP-4 inhibitor, exhibits a slow dissociation from DPP-4. We investigated the sustained effects of saxagliptin on renal DPP-4 activity in a washout study using renal tubular (HK-2 cells, and in a pharmacodynamic study using normal rats. In HK-2 cells, the inhibitory potency of saxagliptin on DPP-4 activity persisted after washout, while that of sitagliptin was clearly reduced. In normal rats, a single treatment of saxagliptin or sitagliptin inhibited the plasma DPP-4 activity to similar levels. The inhibitory action of saxagliptin on the renal DPP-4 activity was retained, even when its inhibitory effect on the plasma DPP-4 activity disappeared. However, the inhibitory action of sitagliptin on the renal DPP-4 activity was abolished in correlation with the inhibition of the plasma DPP-4 activity. In situ staining showed that saxagliptin suppressed the DPP-4 activity in both glomerular and tubular cells and its inhibitory effects were significantly higher than those of sitagliptin. Saxagliptin exerted a sustained inhibitory effect on the renal DPP-4 activity in vitro and in vivo. The long binding action of saxagliptin in renal tubular cells might involve the sustained inhibition of renal DPP-4.

  11. Artemisinin inhibits chloroplast electron transport activity: mode of action.

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    Adyasha Bharati

    Full Text Available Artemisinin, a secondary metabolite produced in Artemisia plant species, besides having antimalarial properties is also phytotoxic. Although, the phytotoxic activity of the compound has been long recognized, no information is available on the mechanism of action of the compound on photosynthetic activity of the plant. In this report, we have evaluated the effect of artemisinin on photoelectron transport activity of chloroplast thylakoid membrane. The inhibitory effect of the compound, under in vitro condition, was pronounced in loosely and fully coupled thylakoids; being strong in the former. The extent of inhibition was drastically reduced in the presence of uncouplers like ammonium chloride or gramicidin; a characteristic feature described for energy transfer inhibitors. The compound, on the other hand, when applied to plants (in vivo, behaved as a potent inhibitor of photosynthetic electron transport. The major site of its action was identified to be the Q(B; the secondary quinone moiety of photosystemII complex. Analysis of photoreduction kinetics of para-benzoquinone and duroquinone suggest that the inhibition leads to formation of low pool of plastoquinol, which becomes limiting for electron flow through photosystemI. Further it was ascertained that the in vivo inhibitory effect appeared as a consequence of the formation of an unidentified artemisinin-metabolite rather than by the interaction of the compound per se. The putative metabolite of artemisinin is highly reactive in instituting the inhibition of photosynthetic electron flow eventually reducing the plant growth.

  12. Potent Inhibitory Effect of Chinese Dietary Spices on Fatty Acid Synthase.

    Science.gov (United States)

    Jiang, Bing; Liang, Yan; Sun, Xuebing; Liu, Xiaoxin; Tian, Weixi; Ma, Xiaofeng

    2015-09-01

    Dietary spices have been adopted in cooking since ancient times to enhance flavor and also as food preservatives and disease remedies. In China, the use of spices and other aromatic plants as food flavoring is an integral part of dietary behavior, but relatively little is known about their functions. Fatty acid synthase (FAS) has been recognized as a remedy target, and its inhibitors might be applied in disease treatment. The present work was designed to assess the inhibitory activities on FAS of spices extracts in Chinese menu. The in vitro inhibitory activities on FAS of 22 extracts of spices were assessed by spectrophotometrically monitoring oxidation of NADPH at 340 nm. Results showed that 20 spices extracts (90.9 %) exhibited inhibitory activities on FAS, with half inhibition concentration (IC(50)) values ranging from 1.72 to 810.7 μg/ml. Among them, seven spices showed strong inhibitory effect with IC(50) values lower than 10 μg/ml. These findings suggest that a large proportion of the dietary spices studied possess promising inhibitory activities on FAS, and subsequently might be applied in the treatment of obesity and obesity-related human diseases.

  13. Inhibitory effect of Xenorhabdus nematophila TB on plant pathogens Phytophthora capsici and Botrytis cinerea in vitro and in planta.

    Science.gov (United States)

    Fang, Xiangling; Zhang, Manrang; Tang, Qian; Wang, Yonghong; Zhang, Xing

    2014-03-06

    Entomopathogenic bacteria Xenorhabdus spp. produce secondary metabolites with potential antimicrobial activity for use in agricultural productions. This study evaluated the inhibitory effect of X. nematophila TB culture on plant pathogens Botrytis cinerea and Phytophthora capsici. The cell-free filtrate of TB culture showed strong inhibitory effects (>90%) on mycelial growth of both pathogens. The methanol-extracted bioactive compounds (methanol extract) of TB culture also had strong inhibitory effects on mycelial growth and spore germinations of both pathogens. The methanol extract (1000 μg/mL) and cell-free filtrate both showed strong therapeutic and protective effects (>70%) on grey mold both in detached tomato fruits and plants, and leaf scorch in pepper plants. This study demonstrates X. nematophila TB produces antimicrobial metabolites of strong activity on plant pathogens, with great potential for controlling tomato grey mold and pepper leaf scorch and being used in integrated disease control to reduce chemical application.

  14. Approximation of wave action flux velocity in strongly sheared mean flows

    Science.gov (United States)

    Banihashemi, Saeideh; Kirby, James T.; Dong, Zhifei

    2017-08-01

    Spectral wave models based on the wave action equation typically use a theoretical framework based on depth uniform current to account for current effects on waves. In the real world, however, currents often have variations over depth. Several recent studies have made use of a depth-weighted current U˜ due to [Skop, R. A., 1987. Approximate dispersion relation for wave-current interactions. J. Waterway, Port, Coastal, and Ocean Eng. 113, 187-195.] or [Kirby, J. T., Chen, T., 1989. Surface waves on vertically sheared flows: approximate dispersion relations. J. Geophys. Res. 94, 1013-1027.] in order to account for the effect of vertical current shear. Use of the depth-weighted velocity, which is a function of wavenumber (or frequency and direction) has been further simplified in recent applications by only utilizing a weighted current based on the spectral peak wavenumber. These applications do not typically take into account the dependence of U˜ on wave number k, as well as erroneously identifying U˜ as the proper choice for current velocity in the wave action equation. Here, we derive a corrected expression for the current component of the group velocity. We demonstrate its consistency using analytic results for a current with constant vorticity, and numerical results for a measured, strongly-sheared current profile obtained in the Columbia River. The effect of choosing a single value for current velocity based on the peak wave frequency is examined, and we suggest an alternate strategy, involving a Taylor series expansion about the peak frequency, which should significantly extend the range of accuracy of current estimates available to the wave model with minimal additional programming and data transfer.

  15. Inhibitory actions of methionine-enkephalin and morphine on the cat carotid chemoreceptors.

    Science.gov (United States)

    McQueen, D S; Ribeiro, J A

    1980-01-01

    1 The effects of intracarotid injections of methionine-enkephalin (Met-enkephalin) and morphine on chemoreceptor activity recorded from the peripheral end of a sectioned carotid sinus nerve have been studied in cats anaesthetized with pentobarbitone. 2 Met-enkephalin caused a rapid, powerful, inhibition of spontaneous chemoreceptor discharge, the intensity and duration of which was dose-dependent. 3 Morphine was a less potent inhibitor of spontaneous chemoreceptor discharge, and the inhibition it evoked was rather variable and tended to be biphasic. Low doses of morphine caused a slight increase in discharge. 4 Naloxone (0.2 mg i.c.) slightly increased spontaneous discharge, greatly reduced the chemo-inhibition caused by morphine, and reduced the inhibitory effect of Met-enkephalin. A higher dose of naloxone (0.8 mg) caused a substantial reduction of the Met-enkephalin effect. 5 Chemo-excitation evoked by intracarotid injections of acetylcholine, CO2-saturated Locke solution, and sodium cyanide were only slightly and somewhat variably reduced following injections of Met-enkephalin, whereas the inhibitory effect of dopamine was potentiated. Following morphine administration, response to acetylcholine and sodium cyanide were reduced slightly, whereas those to CO2 and dopamine were potentiated. 6 Responses to acetylcholine and CO2 were slightly potentiated during infusion of Met-enkephalin (50 micrograms/min, i.c.) and the response to sodium cyanide was slightly reduced. 7 It is concluded that naloxone-sensitive opiate receptors are present in the cat carotid body; when activated they cause inhibition of spontaneous chemoreceptor discharge. The physiological role of these receptors and the identity of any endogenous ligand remains to be established.

  16. Brain ageing changes proteoglycan sulfation, rendering perineuronal nets more inhibitory.

    Science.gov (United States)

    Foscarin, Simona; Raha-Chowdhury, Ruma; Fawcett, James W; Kwok, Jessica C F

    2017-06-28

    Chondroitin sulfate (CS) proteoglycans in perineuronal nets (PNNs) from the central nervous system (CNS) are involved in the control of plasticity and memory. Removing PNNs reactivates plasticity and restores memory in models of Alzheimer's disease and ageing. Their actions depend on the glycosaminoglycan (GAG) chains of CS proteoglycans, which are mainly sulfated in the 4 (C4S) or 6 (C6S) positions. While C4S is inhibitory, C6S is more permissive to axon growth, regeneration and plasticity. C6S decreases during critical period closure. We asked whether there is a late change in CS-GAG sulfation associated with memory loss in aged rats. Immunohistochemistry revealed a progressive increase in C4S and decrease in C6S from 3 to 18 months. GAGs extracted from brain PNNs showed a large reduction in C6S at 12 and 18 months, increasing the C4S/C6S ratio. There was no significant change in mRNA levels of the chondroitin sulfotransferases. PNN GAGs were more inhibitory to axon growth than those from the diffuse extracellular matrix. The 18-month PNN GAGs were more inhibitory than 3-month PNN GAGs. We suggest that the change in PNN GAG sulfation in aged brains renders the PNNs more inhibitory, which lead to a decrease in plasticity and adversely affect memory.

  17. Two distinct and competitive pathways confer the cellcidal actions of artemisinins

    Directory of Open Access Journals (Sweden)

    Chen Sun

    2015-01-01

    Full Text Available The biological actions of artemisinin (ART, an antimalarial drug derived from Artemisia annua, remain poorly understood and controversial. Besides potent antimalarial activity, some of artemisinin derivatives (together with artemisinin, hereafter referred to as ARTs, in particular dihydroartemisinin (DHA, are also associated with anticancer and other antiparasitic activities. In this study, we used baker’s yeast Saccharomyces cerevisiae as cellular and genetic model to investigate the molecular and cellular properties of ARTs. Two clearly separable pathways exist. While all ARTs exhibit potent anti-mitochondrial actions as shown before, DHA exerts an additional strong heme-dependent, likely mitochondria-independent inhibitory action. More importantly, heme antagonizes the mitochondria-dependent cellcidal action. Indeed, when heme synthesis was inhibited, the mitochondria-dependent cellcidal action of ARTs could be dramatically strengthened, and significant yeast growth inhibition at as low as 100 nM ART, an increase of about 25 folds in sensitivity, was observed. We conclude that ARTs are endowed with two major and distinct types of properties: a potent and specific mitochondria-dependent reaction and a more general and less specific heme-mediated reaction. The competitive nature of these two actions could be explained by their shared source of the consumable ARTs, so that inhibition of the heme-mediated degradation pathway would enable more ARTs to be available for the mitochondrial action. These properties of ARTs can be used to interpret the divergent antimalarial and anticancer actions of ARTs.

  18. Preschool Inhibitory Control Predicts ADHD Group Status and Inhibitory Weakness in School.

    Science.gov (United States)

    Jacobson, Lisa A; Schneider, Heather; Mahone, E Mark

    2017-12-26

    Discriminative utility of performance measures of inhibitory control was examined in preschool children with and without ADHD to determine whether performance measures added to diagnostic prediction and to prediction of informant-rated day-to-day executive function. Children ages 4-5 years (N = 105, 61% boys; 54 ADHD, medication-naïve) were assessed using performance measures (Auditory Continuous Performance Test for Preschoolers-Commission errors, Conflicting Motor Response Test, NEPSY Statue) and caregiver (parent, teacher) ratings of inhibition (Behavior Rating Inventory of Executive Function-Preschool version). Performance measures and parent and teacher reports of inhibitory control significantly and uniquely predicted ADHD group status; however, performance measures did not add to prediction of group status beyond parent reports. Performance measures did significantly predict classroom inhibitory control (teacher ratings), over and above parent reports of inhibitory control. Performance measures of inhibitory control may be adequate predictors of ADHD status and good predictors of young children's classroom inhibitory control, demonstrating utility as components of clinical assessments. © The Author(s) 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  19. New Biflavonoids with α-Glucosidase and Pancreatic Lipase Inhibitory Activities from Boesenbergia rotunda

    Directory of Open Access Journals (Sweden)

    Nutputsorn Chatsumpun

    2017-10-01

    Full Text Available Roots of Boesenbergia rotunda (L. Mansf. are prominent ingredients in the cuisine of several Asian countries, including Thailand, Malaysia, Indonesia, India, and China. An extract prepared from the roots of this plant showed strong inhibitory activity against enzymes α-glucosidase and pancreatic lipase and was subjected to chromatographic separation to identify the active components. Three new biflavonoids of the flavanone-chalcone type (9, 12, and 13 were isolated, along with 12 known compounds. Among the 15 isolates, the three new compounds showed stronger inhibitory activity against α-glucosidase than the drug acarbose but displayed lower pancreatic lipase inhibitory effect than the drug orlistat. The results indicated the potential of B. rotunda roots as a functional food for controlling after-meal blood glucose levels.

  20. “Weak direct” and “Strong indirect” interactions are the mode of action of food factors

    Directory of Open Access Journals (Sweden)

    Tetsuya Konishi

    2014-06-01

    Full Text Available Age-dependent and lifestyle related diseases such as metabolic syndromes have become a social problem worldwide. Since these disorders are closely related to dietary lifestyle, the old saying “foods are medicine” is now being re-evaluated. Thus, dietary protection against these diseases is attracting much attention. As research into functional foods advances, a book of knowledge is being accumulated on the active ingredients, termed “food factors”, present in food resources. Identifying such molecules usually follows the conventional methodology used for finding drug candidates from natural resources. The question has arisen as to whether the mode of action of food factors as molecules is the same as that of drugs. In this article, the functional properties of food factors and drugs are comparatively reviewed and the characteristic features of food factor function is discussed, based on the idea of “weak direct” and “strong indirect” actions of food factors to their receptors

  1. Action Video Gaming and Cognitive Control: Playing First Person Shooter Games Is Associated with Improved Action Cascading but Not Inhibition

    Science.gov (United States)

    Steenbergen, Laura; Sellaro, Roberta; Stock, Ann-Kathrin; Beste, Christian; Colzato, Lorenza S.

    2015-01-01

    There is a constantly growing interest in developing efficient methods to enhance cognitive functioning and/or to ameliorate cognitive deficits. One particular line of research focuses on the possibly cognitive enhancing effects that action video game (AVG) playing may have on game players. Interestingly, AVGs, especially first person shooter games, require gamers to develop different action control strategies to rapidly react to fast moving visual and auditory stimuli, and to flexibly adapt their behaviour to the ever-changing context. This study investigated whether and to what extent experience with such videogames is associated with enhanced performance on cognitive control tasks that require similar abilities. Experienced action videogame-players (AVGPs) and individuals with little to no videogame experience (NVGPs) performed a stop-change paradigm that provides a relatively well-established diagnostic measure of action cascading and response inhibition. Replicating previous findings, AVGPs showed higher efficiency in response execution, but not improved response inhibition (i.e. inhibitory control), as compared to NVGPs. More importantly, compared to NVGPs, AVGPs showed enhanced action cascading processes when an interruption (stop) and a change towards an alternative response were required simultaneously, as well as when such a change had to occur after the completion of the stop process. Our findings suggest that playing AVGs is associated with enhanced action cascading and multi-component behaviour without affecting inhibitory control. PMID:26655929

  2. Action Video Gaming and Cognitive Control: Playing First Person Shooter Games Is Associated with Improved Action Cascading but Not Inhibition.

    Directory of Open Access Journals (Sweden)

    Laura Steenbergen

    Full Text Available There is a constantly growing interest in developing efficient methods to enhance cognitive functioning and/or to ameliorate cognitive deficits. One particular line of research focuses on the possibly cognitive enhancing effects that action video game (AVG playing may have on game players. Interestingly, AVGs, especially first person shooter games, require gamers to develop different action control strategies to rapidly react to fast moving visual and auditory stimuli, and to flexibly adapt their behaviour to the ever-changing context. This study investigated whether and to what extent experience with such videogames is associated with enhanced performance on cognitive control tasks that require similar abilities. Experienced action videogame-players (AVGPs and individuals with little to no videogame experience (NVGPs performed a stop-change paradigm that provides a relatively well-established diagnostic measure of action cascading and response inhibition. Replicating previous findings, AVGPs showed higher efficiency in response execution, but not improved response inhibition (i.e. inhibitory control, as compared to NVGPs. More importantly, compared to NVGPs, AVGPs showed enhanced action cascading processes when an interruption (stop and a change towards an alternative response were required simultaneously, as well as when such a change had to occur after the completion of the stop process. Our findings suggest that playing AVGs is associated with enhanced action cascading and multi-component behaviour without affecting inhibitory control.

  3. Action Video Gaming and Cognitive Control: Playing First Person Shooter Games Is Associated with Improved Action Cascading but Not Inhibition.

    Science.gov (United States)

    Steenbergen, Laura; Sellaro, Roberta; Stock, Ann-Kathrin; Beste, Christian; Colzato, Lorenza S

    2015-01-01

    There is a constantly growing interest in developing efficient methods to enhance cognitive functioning and/or to ameliorate cognitive deficits. One particular line of research focuses on the possibly cognitive enhancing effects that action video game (AVG) playing may have on game players. Interestingly, AVGs, especially first person shooter games, require gamers to develop different action control strategies to rapidly react to fast moving visual and auditory stimuli, and to flexibly adapt their behaviour to the ever-changing context. This study investigated whether and to what extent experience with such videogames is associated with enhanced performance on cognitive control tasks that require similar abilities. Experienced action videogame-players (AVGPs) and individuals with little to no videogame experience (NVGPs) performed a stop-change paradigm that provides a relatively well-established diagnostic measure of action cascading and response inhibition. Replicating previous findings, AVGPs showed higher efficiency in response execution, but not improved response inhibition (i.e. inhibitory control), as compared to NVGPs. More importantly, compared to NVGPs, AVGPs showed enhanced action cascading processes when an interruption (stop) and a change towards an alternative response were required simultaneously, as well as when such a change had to occur after the completion of the stop process. Our findings suggest that playing AVGs is associated with enhanced action cascading and multi-component behaviour without affecting inhibitory control.

  4. Localization of chondromodulin-I at the feto-maternal interface and its inhibitory actions on trophoblast invasion in vitro

    Directory of Open Access Journals (Sweden)

    Kondo Jun

    2011-08-01

    Full Text Available Abstract Background Chondromodulin-I (ChM-I is an anti-angiogenic glycoprotein that is specifically localized at the extracellular matrix of the avascular mesenchyme including cartilage and cardiac valves. In this study, we characterized the expression pattern of ChM-I during early pregnancy in mice in vivo and its effect on invasion of trophoblastic cells into Matrigel in vitro. Results Northern blot analysis clearly indicated that ChM-I transcripts were expressed in the pregnant mouse uterus at 6.5-9.5 days post coitum. In situ hybridization and immunohistochemistry revealed that ChM-I was localized to the mature decidua surrounding the matrix metalloproteinase-9 (MMP-9-expressing trophoblasts. Consistent with this observation, the expression of ChM-I mRNA was induced in decidualizing endometrial stromal cells in vitro, in response to estradiol and progesterone. Recombinant human ChM-I (rhChM-I markedly inhibited the invasion through Matrigel as well as the chemotactic migration of rat Rcho-1 trophoblast cells in a manner independent of MMP activation. Conclusions This study demonstrates the inhibitory action of ChM-I on trophoblast migration and invasion, implying the potential role of the ChM-I expression in decidual cells for the regulated tissue remodeling and angiogenesis at feto-maternal interface.

  5. Catalytic and inhibitory effects of thechnetium on reduction processes

    International Nuclear Information System (INIS)

    Grases, F.; Genestar, C.; March, J.G.; March, P.

    1986-01-01

    Interactions between technetium and some anthraquinones and tartrazin in the presence of tin(II) are described. It was found that whereas the reductive process between Sn(II) and 1-amino-4-hydroxyanthraquinone is catalyzed by technetium, the reduction of tartrazin is inhibited by this element. Study of such process seems to indicate that the catalytic effect of technetium on the reduction processes is due to Tc(V) action whereas the inhibitory effect is due to the Tc(IV) species. (author)

  6. Death and rebirth of neural activity in sparse inhibitory networks

    Science.gov (United States)

    Angulo-Garcia, David; Luccioli, Stefano; Olmi, Simona; Torcini, Alessandro

    2017-05-01

    Inhibition is a key aspect of neural dynamics playing a fundamental role for the emergence of neural rhythms and the implementation of various information coding strategies. Inhibitory populations are present in several brain structures, and the comprehension of their dynamics is strategical for the understanding of neural processing. In this paper, we clarify the mechanisms underlying a general phenomenon present in pulse-coupled heterogeneous inhibitory networks: inhibition can induce not only suppression of neural activity, as expected, but can also promote neural re-activation. In particular, for globally coupled systems, the number of firing neurons monotonically reduces upon increasing the strength of inhibition (neuronal death). However, the random pruning of connections is able to reverse the action of inhibition, i.e. in a random sparse network a sufficiently strong synaptic strength can surprisingly promote, rather than depress, the activity of neurons (neuronal rebirth). Thus, the number of firing neurons reaches a minimum value at some intermediate synaptic strength. We show that this minimum signals a transition from a regime dominated by neurons with a higher firing activity to a phase where all neurons are effectively sub-threshold and their irregular firing is driven by current fluctuations. We explain the origin of the transition by deriving a mean field formulation of the problem able to provide the fraction of active neurons as well as the first two moments of their firing statistics. The introduction of a synaptic time scale does not modify the main aspects of the reported phenomenon. However, for sufficiently slow synapses the transition becomes dramatic, and the system passes from a perfectly regular evolution to irregular bursting dynamics. In this latter regime the model provides predictions consistent with experimental findings for a specific class of neurons, namely the medium spiny neurons in the striatum.

  7. Inhibitory action of chlorophyllin of autosome recessive lethals induced by irradiation; Accion inhibidora de la clorofilina de letales recesivos autosonicos inducidos por irradiacion

    Energy Technology Data Exchange (ETDEWEB)

    Salceda, V.M.; Pimentel, P.A.E.; Cruces, M.P. [ININ, 52045 Ocoyoacac, Estado de Mexico (Mexico)]. e-mail: vmss@nuclear.inin.mx

    2006-07-01

    The chlorolin is a sodium salt of the chlorophyll that has a strong protective action of the damage induced by different agents so much physical as chemical. In Drosophila there is reported this effect in somatic cells. In contrast, in germinal cells using tests with the sexual chromosomes has not been found such inhibitory action. For this reason, in this occasion we will refer to the effect of the lethality induced in autosome chromosomes, in particular to the chromosome II of this species. For such effect groups of males of the line Canton-S its were pre-treated for 24h with or without 69 mm of CCS and later on treaties with or without 40 Gy of gamma irradiation. The males were then subjected to the technical Cy L / Pm for the detection of recessive lethals. In the third generation the respective counts of the descendant of each one of them to determine the corresponding categories for each extracted chromosome were made. To be mendelian crosses it is expected for a normal chromosome a proportion 2:1 of individuals with genotype Cy L / +: +/+. The absence of individuals +/+ it is indicative of a lethal gene, until 10% of these individuals of each male's total descendant, it is considered that is carrying of a semi lethal gene. The sum of lethal and semi lethals constitutes the category detrimental. The obtained results indicated that the pre-treatment with CCS reduces in a significant way the frequency of induced lethals by 40 Gy of gamma rays. The fact that an effect inhibitor has not been observed in the test of recessive lethal bound to the sex obtained previously, it contrasts with the effect observed in the chromosome II, results of this study and with the one observed in the chromosome III in somatic cells. The above-mentioned shows a differential action of the CCS between sexual chromosomes and autosomal before the effect of the gamma radiation. At the moment we don't have an explanation to these evidences. To evaluate the action of the

  8. Inhibitory action of chlorophyllin of autosome recessive lethals induced by irradiation; Accion inhibidora de la clorofilina de letales recesivos autosonicos inducidos por irradiacion

    Energy Technology Data Exchange (ETDEWEB)

    Salceda, V M; Pimentel, P A.E.; Cruces, M P [ININ, 52045 Ocoyoacac, Estado de Mexico (Mexico)

    2006-07-01

    The chlorolin is a sodium salt of the chlorophyll that has a strong protective action of the damage induced by different agents so much physical as chemical. In Drosophila there is reported this effect in somatic cells. In contrast, in germinal cells using tests with the sexual chromosomes has not been found such inhibitory action. For this reason, in this occasion we will refer to the effect of the lethality induced in autosome chromosomes, in particular to the chromosome II of this species. For such effect groups of males of the line Canton-S its were pre-treated for 24h with or without 69 mm of CCS and later on treaties with or without 40 Gy of gamma irradiation. The males were then subjected to the technical Cy L / Pm for the detection of recessive lethals. In the third generation the respective counts of the descendant of each one of them to determine the corresponding categories for each extracted chromosome were made. To be mendelian crosses it is expected for a normal chromosome a proportion 2:1 of individuals with genotype Cy L / +: +/+. The absence of individuals +/+ it is indicative of a lethal gene, until 10% of these individuals of each male's total descendant, it is considered that is carrying of a semi lethal gene. The sum of lethal and semi lethals constitutes the category detrimental. The obtained results indicated that the pre-treatment with CCS reduces in a significant way the frequency of induced lethals by 40 Gy of gamma rays. The fact that an effect inhibitor has not been observed in the test of recessive lethal bound to the sex obtained previously, it contrasts with the effect observed in the chromosome II, results of this study and with the one observed in the chromosome III in somatic cells. The above-mentioned shows a differential action of the CCS between sexual chromosomes and autosomal before the effect of the gamma radiation. At the moment we don't have an explanation to these evidences. To evaluate the action of the chlorophyllin on

  9. Preferential binding of growth inhibitory prostaglandins by the target protein of a carcinogen

    Energy Technology Data Exchange (ETDEWEB)

    Khan, S.H.; Sorof, S. (Fox Chase Cancer Center, Philadelphia, PA (United States))

    1990-12-01

    Liver fatty acid binding protein (L-FABP) is the principal target protein of the hepatic carcinogen N-(2-fluorenyl)acetamide (2-acetylaminofluorene) in rat liver. In addition, the cyclopentenone prostaglandins (PG), PGA, PGJ{sub 2}, and {Delta}{sup 12}-PGJ{sub 2}, inhibit the growth of many cell types in vitro. This report describes the preferential binding of the growth inhibitory prostaglandins by L-FABP and the reversible inhibition of thymidine incorporation into DNA by PGA{sub 2} and {Delta}{sup 12}-PGJ{sub 2} in primary cultures of purified rat hepatocytes. As a model ligand, ({sup 3}H)PGA{sub 1} bound to L-FABP specifically, reversibly, rapidly, and with high affinity. Its dissociation constants were 134 nM (high affinity) and 3.6 {mu}M (low affinity). The high-affinity finding of ({sup 3}H)PGA{sup 1} correlated with their growth inhibitory activities reported previously and here. The in vitro actions of L-FABP are compatible with those of a specific and dissociable carrier of growth inhibitory prostaglandins in rat hepatocytes and suggest that the carcinogen may usurp the cellular machinery of the growth inhibitory prostaglandins.

  10. Rapid Screening of Active Components with an Osteoclastic Inhibitory Effect in Herba epimedii Using Quantitative Pattern–Activity Relationships Based on Joint-Action Models

    Directory of Open Access Journals (Sweden)

    Xiao-Yan Yuan

    2017-10-01

    Full Text Available Screening of bioactive components is important for modernization and quality control of herbal medicines, while the traditional bioassay-guided phytochemical approach is time-consuming and laborious. The presented study proposes a strategy for rapid screening of active components from herbal medicines. As a case study, the quantitative pattern–activity relationship (QPAR between compounds and the osteoclastic inhibitory effect of Herba epimedii, a widely used herbal medicine in China, were investigated based on joint models. For model construction, standard mixtures data showed that the joint-action models are better than the partial least-squares (PLS model. Then, the Good2bad value, which could reflect components’ importance based on Monte Carlo sampling, was coupled with the joint-action models for screening of active components. A compound (baohuoside I and a component composed of compounds with retention times in the 6.9–7.9 min range were selected by our method. Their inhibition rates were higher than icariin, the key bioactive compound in Herba epimedii, which could inhibit osteoclast differentiation and bone resorption in a previous study. Meanwhile, the half-maximal effective concentration, namely, EC50 value of the selected component was 7.54 μg/mL, much smaller than that of baohuoside I—77 μg/mL—which indicated that there is synergistic action between compounds in the selected component. The results clearly show our proposed method is simple and effective in screening the most-bioactive components and compounds, as well as drug-lead components, from herbal medicines.

  11. Effects of incentives, age, and behavior on brain activation during inhibitory control: A longitudinal fMRI study

    Directory of Open Access Journals (Sweden)

    David J. Paulsen

    2015-02-01

    Full Text Available We investigated changes in brain function supporting inhibitory control under age-controlled incentivized conditions, separating age- and performance-related activation in an accelerated longitudinal design including 10- to 22-year-olds. Better inhibitory control correlated with striatal activation during neutral trials, while Age X Behavior interactions in the striatum indicated that in the absence of extrinsic incentives, younger subjects with greater reward circuitry activation successfully engage in greater inhibitory control. Age was negatively correlated with ventral amygdala activation during Loss trials, suggesting that amygdala function more strongly mediates bottom-up processing earlier in development when controlling the negative aspects of incentives to support inhibitory control. Together, these results indicate that with development, reward-modulated cognitive control may be supported by incentive processing transitions in the amygdala, and from facilitative to obstructive striatal function during inhibitory control.

  12. Global actions of nicotine on the striatal microcircuit.

    Science.gov (United States)

    Plata, Víctor; Duhne, Mariana; Pérez-Ortega, Jesús; Hernández-Martinez, Ricardo; Rueda-Orozco, Pavel; Galarraga, Elvira; Drucker-Colín, René; Bargas, José

    2013-01-01

    what is the predominant action induced by the activation of cholinergic-nicotinic receptors (nAChrs) in the striatal network given that nAChrs are expressed by several elements of the circuit: cortical terminals, dopamine terminals, and various striatal GABAergic interneurons. To answer this question some type of multicellular recording has to be used without losing single cell resolution. Here, we used calcium imaging and nicotine. It is known that in the presence of low micromolar N-Methyl-D-aspartate (NMDA), the striatal microcircuit exhibits neuronal activity consisting in the spontaneous synchronization of different neuron pools that interchange their activity following determined sequences. The striatal circuit also exhibits profuse spontaneous activity in pathological states (without NMDA) such as dopamine depletion. However, in this case, most pathological activity is mostly generated by the same neuron pool. Here, we show that both types of activity are inhibited during the application of nicotine. Nicotine actions were blocked by mecamylamine, a non-specific antagonist of nAChrs. Interestingly, inhibitory actions of nicotine were also blocked by the GABAA-receptor antagonist bicuculline, in which case, the actions of nicotine on the circuit became excitatory and facilitated neuronal synchronization. We conclude that the predominant action of nicotine in the striatal microcircuit is indirect, via the activation of networks of inhibitory interneurons. This action inhibits striatal pathological activity in early Parkinsonian animals almost as potently as L-DOPA.

  13. Mitochondrial reactive oxygen species regulate the strength of inhibitory GABA-mediated synaptic transmission

    Science.gov (United States)

    Accardi, Michael V.; Daniels, Bryan A.; Brown, Patricia M. G. E.; Fritschy, Jean-Marc; Tyagarajan, Shiva K.; Bowie, Derek

    2014-01-01

    Neuronal communication imposes a heavy metabolic burden in maintaining ionic gradients essential for action potential firing and synaptic signalling. Although cellular metabolism is known to regulate excitatory neurotransmission, it is still unclear whether the brain’s energy supply affects inhibitory signalling. Here we show that mitochondrial-derived reactive oxygen species (mROS) regulate the strength of postsynaptic GABAA receptors at inhibitory synapses of cerebellar stellate cells. Inhibition is strengthened through a mechanism that selectively recruits α3-containing GABAA receptors into synapses with no discernible effect on resident α1-containing receptors. Since mROS promotes the emergence of postsynaptic events with unique kinetic properties, we conclude that newly recruited α3-containing GABAA receptors are activated by neurotransmitter released onto discrete postsynaptic sites. Although traditionally associated with oxidative stress in neurodegenerative disease, our data identify mROS as a putative homeostatic signalling molecule coupling cellular metabolism to the strength of inhibitory transmission.

  14. Macrophage migration inhibitory factor (MIF) modulates trophic signaling through interaction with serine protease HTRA1

    DEFF Research Database (Denmark)

    Fex Svenningsen, Åsa; Loering, Svenja; Sørensen, Anna Lahn

    2017-01-01

    Macrophage migration inhibitory factor (MIF), a small conserved protein, is abundant in the immune- and central nervous system (CNS). MIF has several receptors and binding partners that can modulate its action on a cel-lular level. It is upregulated in neurodegenerative diseases and cancer although...

  15. β-Nicotinamide adenine dinucleotide acts at prejunctional adenosine A1 receptors to suppress inhibitory musculomotor neurotransmission in guinea pig colon and human jejunum

    Science.gov (United States)

    Wang, Guo-Du; Wang, Xi-Yu; Liu, Sumei; Xia, Yun; Zou, Fei; Qu, Meihua; Needleman, Bradley J.; Mikami, Dean J.

    2015-01-01

    Intracellular microelectrodes were used to record neurogenic inhibitory junction potentials in the intestinal circular muscle coat. Electrical field stimulation was used to stimulate intramural neurons and evoke contraction of the smooth musculature. Exposure to β-nicotinamide adenine dinucleotide (β-NAD) did not alter smooth muscle membrane potential in guinea pig colon or human jejunum. ATP, ADP, β-NAD, and adenosine, as well as the purinergic P2Y1 receptor antagonists MRS 2179 and MRS 2500 and the adenosine A1 receptor agonist 2-chloro-N6-cyclopentyladenosine, each suppressed inhibitory junction potentials in guinea pig and human preparations. β-NAD suppressed contractile force of twitch-like contractions evoked by electrical field stimulation in guinea pig and human preparations. P2Y1 receptor antagonists did not reverse this action. Stimulation of adenosine A1 receptors with 2-chloro-N6-cyclopentyladenosine suppressed the force of twitch contractions evoked by electrical field stimulation in like manner to the action of β-NAD. Blockade of adenosine A1 receptors with 8-cyclopentyl-1,3-dipropylxanthine suppressed the inhibitory action of β-NAD on the force of electrically evoked contractions. The results do not support an inhibitory neurotransmitter role for β-NAD at intestinal neuromuscular junctions. The data suggest that β-NAD is a ligand for the adenosine A1 receptor subtype expressed by neurons in the enteric nervous system. The influence of β-NAD on intestinal motility emerges from adenosine A1 receptor-mediated suppression of neurotransmitter release at inhibitory neuromuscular junctions. PMID:25813057

  16. Sequentially switching cell assemblies in random inhibitory networks of spiking neurons in the striatum.

    Science.gov (United States)

    Ponzi, Adam; Wickens, Jeff

    2010-04-28

    The striatum is composed of GABAergic medium spiny neurons with inhibitory collaterals forming a sparse random asymmetric network and receiving an excitatory glutamatergic cortical projection. Because the inhibitory collaterals are sparse and weak, their role in striatal network dynamics is puzzling. However, here we show by simulation of a striatal inhibitory network model composed of spiking neurons that cells form assemblies that fire in sequential coherent episodes and display complex identity-temporal spiking patterns even when cortical excitation is simply constant or fluctuating noisily. Strongly correlated large-scale firing rate fluctuations on slow behaviorally relevant timescales of hundreds of milliseconds are shown by members of the same assembly whereas members of different assemblies show strong negative correlation, and we show how randomly connected spiking networks can generate this activity. Cells display highly irregular spiking with high coefficients of variation, broadly distributed low firing rates, and interspike interval distributions that are consistent with exponentially tailed power laws. Although firing rates vary coherently on slow timescales, precise spiking synchronization is absent in general. Our model only requires the minimal but striatally realistic assumptions of sparse to intermediate random connectivity, weak inhibitory synapses, and sufficient cortical excitation so that some cells are depolarized above the firing threshold during up states. Our results are in good qualitative agreement with experimental studies, consistent with recently determined striatal anatomy and physiology, and support a new view of endogenously generated metastable state switching dynamics of the striatal network underlying its information processing operations.

  17. [Inhibitory mechanism of ifenprodil tartrate on rabbit platelet aggregation].

    Science.gov (United States)

    Irino, O; Saitoh, K; Hayashi, T; Ohkubo, K

    1985-05-01

    The effects of dl-erythro-4-benzyl-alpha-(4-hydroxyphenyl)-beta-methyl-l-piperidine-eth anol tartrate (ifenprodil tartrate) on rabbit platelet aggregation in vitro and ex vivo were studied. Ifenprodil tartrate inhibited platelet aggregation in vitro induced by ADP, collagen and epinephrine. It also inhibited 5-hydroxytryptamine (5-HT) uptake into platelets and 5-HT release from platelets. Since these inhibitory effects of ifenprodil tartrate on the functions of rabbit platelets were similar to the effects of imipramine, the effects of ifenprodil tartrate may be due to the stabilizing action of ifenprodil tartrate on the platelet membrane. The platelet aggregation by ADP was significantly inhibited in rabbits after oral administration of ifenprodil tartrate, the maximal plasma level of ifenprodil being reached at 20 ng/ml ex vivo, while the maximal level was only 1/40 of the minimal concentration of ifenprodil tartrate necessary to inhibit platelet aggregation in vitro. These results indicate that factors other than ifenprodil tartrate acting directly on the platelets (e.g., PGI2 which is an endogenous inhibitor of platelet aggregation) are involved in inducing the inhibitory effects of ifenprodil tartrate on platelet aggregation ex vivo. The effects of ifenprodil tartrate on both PGI2 release from the aorta and the inhibitory effects of PGI2 on platelet aggregation in vitro were investigated: PGI2 was found to intensify the inhibitory effects of ifenprodil tartrate on platelet aggregation in vitro, but there was little effect, if any, on PGI2 release. Therefore, it is considered that the ex vivo effects of ifenprodil tartrate might be due to its interaction with endogenous PGI2 in the blood.

  18. Comprehension of Action Negation Involves Inhibitory Simulation

    Directory of Open Access Journals (Sweden)

    Francesco eForoni

    2013-05-01

    Full Text Available Previous research suggests that action language is comprehended by activating the motor system. We report a study, investigating a critical question in this research field: Do negative sentences activate the motor system? Participants were exposed to sentences in the affirmation and negation forms while the zygomatic muscle activity on the left side of the face was continuously measured (Electromyography technique: EMG. Sentences were descriptions of emotional expressions that mapped either directly upon the zygomatic muscle (e.g., ‘I am smiling’ or did not (e.g., ‘I am frowning’. Reading sentences involving the negation of the activity of a specific muscle (zygomatic major - I am not smiling is shown to lead to the inhibition of this muscle. Reading sentences involving the affirmative form instead (I am smiling leads to the activation of zygomatic mucle. In contrast, sentences describing an activity that is irrelevant to the zygomatic muscle (e.g., ‘I am frowning’ or ‘I am not frowning’ produce no muscle activity. These results extend the range of simulation models to negation and by implication to an abstract domain. We discuss how this research contributes to the grounding of abstract and concrete concepts.

  19. Memorable objects are more susceptible to forgetting: Evidence for the inhibitory account of retrieval-induced forgetting.

    Science.gov (United States)

    Reppa, I; Williams, K E; Worth, E R; Greville, W J; Saunders, J

    2017-11-01

    Retrieval of target information can cause forgetting for related, but non-retrieved, information - retrieval-induced forgetting (RIF). The aim of the current studies was to examine a key prediction of the inhibitory account of RIF - interference dependence - whereby 'strong' non-retrieved items are more likely to interfere during retrieval and therefore, are more susceptible to RIF. Using visual objects allowed us to examine and contrast one index of item strength -object typicality, that is, how typical of its category an object is. Experiment 1 provided proof of concept for our variant of the recognition practice paradigm. Experiment 2 tested the prediction of the inhibitory account that the magnitude of RIF for natural visual objects would be dependent on item strength. Non-typical objects were more memorable overall than typical objects. We found that object memorability (as determined by typicality) influenced RIF with significant forgetting occurring for the memorable (non-typical), but not non-memorable (typical), objects. The current findings strongly support an inhibitory account of retrieval-induced forgetting. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Rational Decision-Making in Inhibitory Control

    Science.gov (United States)

    Shenoy, Pradeep; Yu, Angela J.

    2011-01-01

    An important aspect of cognitive flexibility is inhibitory control, the ability to dynamically modify or cancel planned actions in response to changes in the sensory environment or task demands. We formulate a probabilistic, rational decision-making framework for inhibitory control in the stop signal paradigm. Our model posits that subjects maintain a Bayes-optimal, continually updated representation of sensory inputs, and repeatedly assess the relative value of stopping and going on a fine temporal scale, in order to make an optimal decision on when and whether to go on each trial. We further posit that they implement this continual evaluation with respect to a global objective function capturing the various reward and penalties associated with different behavioral outcomes, such as speed and accuracy, or the relative costs of stop errors and go errors. We demonstrate that our rational decision-making model naturally gives rise to basic behavioral characteristics consistently observed for this paradigm, as well as more subtle effects due to contextual factors such as reward contingencies or motivational factors. Furthermore, we show that the classical race model can be seen as a computationally simpler, perhaps neurally plausible, approximation to optimal decision-making. This conceptual link allows us to predict how the parameters of the race model, such as the stopping latency, should change with task parameters and individual experiences/ability. PMID:21647306

  1. Rational decision-making in inhibitory control.

    Science.gov (United States)

    Shenoy, Pradeep; Yu, Angela J

    2011-01-01

    An important aspect of cognitive flexibility is inhibitory control, the ability to dynamically modify or cancel planned actions in response to changes in the sensory environment or task demands. We formulate a probabilistic, rational decision-making framework for inhibitory control in the stop signal paradigm. Our model posits that subjects maintain a Bayes-optimal, continually updated representation of sensory inputs, and repeatedly assess the relative value of stopping and going on a fine temporal scale, in order to make an optimal decision on when and whether to go on each trial. We further posit that they implement this continual evaluation with respect to a global objective function capturing the various reward and penalties associated with different behavioral outcomes, such as speed and accuracy, or the relative costs of stop errors and go errors. We demonstrate that our rational decision-making model naturally gives rise to basic behavioral characteristics consistently observed for this paradigm, as well as more subtle effects due to contextual factors such as reward contingencies or motivational factors. Furthermore, we show that the classical race model can be seen as a computationally simpler, perhaps neurally plausible, approximation to optimal decision-making. This conceptual link allows us to predict how the parameters of the race model, such as the stopping latency, should change with task parameters and individual experiences/ability.

  2. Inhibitory effects of chickpea and Tribulus terrestris on lipase, α-amylase and α-glucosidase.

    Science.gov (United States)

    Ercan, Pınar; El, Sedef Nehir

    2016-08-15

    The total saponin content and its in vitro bioaccessibilities in Tribulus terrestris and chickpea were determined by a static in vitro digestion method (COST FA1005 Action INFOGEST). Also, in vitro inhibitory effects of the chosen food samples on lipid and starch digestive enzymes were determined by evaluating the lipase, α-amylase and α-glucosidase activities. The tested T. terrestris and chickpea showed inhibitory activity against α-glucosidase (IC50 6967 ± 343 and 2885 ± 85.4 μg/ml, respectively) and α-amylase (IC50 343 ± 26.2 and 167 ± 6.12 μg/ml, respectively). The inhibitory activities of T. terrestris and chickpea against lipase were 15.3 ± 2.03 and 9.74 ± 1.09 μg/ml, respectively. The present study provides the first evidence that these food samples (T. terrestris, chickpea) are potent inhibitors of key enzymes in digestion of carbohydrates and lipids in vitro. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Global actions of nicotine on the striatal microcircuit

    Directory of Open Access Journals (Sweden)

    Victor E Plata

    2013-11-01

    Full Text Available The question to solve in the present work is: what is the predominant action induced by the activation of cholinergic-nicotinic receptors (nAChrs in the striatal network given that nAChrs are expressed by several elements of the circuit: cortical terminals, dopamine terminals, and various striatal GABAergic interneurons. To answer this question some type of multicellular recording has to be used without losing single cell resolution. Here, we used calcium imaging and nicotine. It is known that in the presence of low micromolar N-Methyl-D-aspartate (NMDA, the striatal microcircuit exhibits neuronal activity consisting in the spontaneous synchronization of different neuron pools that interchange their activity following determined sequences. The striatal circuit also exhibits profuse spontaneous activity in pathological states (without NMDA such as dopamine depletion. However, in this case, most pathological activity is mostly generated by the same neuron pool. Here, we show that both types of activity are inhibited during the application of nicotine. Nicotine actions were blocked by mecamylamine, a non specific antagonist of nAChrs. Interestingly, inhibitory actions of nicotine were also blocked by the GABAA-receptor antagonist bicuculline, in which case, the actions of nicotine on the circuit became excitatory and facilitated neuronal synchronization. We conclude that the predominant action of nicotine in the striatal microcircuit is indirect, via the activation of networks of inhibitory interneurons. This action inhibits striatal pathological activity in early Parkinsonian animals almost as potently as L-DOPA.

  4. An NMDA Receptor-Dependent Mechanism Underlies Inhibitory Synapse Development

    Directory of Open Access Journals (Sweden)

    Xinglong Gu

    2016-01-01

    Full Text Available In the mammalian brain, GABAergic synaptic transmission provides inhibitory balance to glutamatergic excitatory drive and controls neuronal output. The molecular mechanisms underlying the development of GABAergic synapses remain largely unclear. Here, we report that NMDA-type ionotropic glutamate receptors (NMDARs in individual immature neurons are the upstream signaling molecules essential for GABAergic synapse development, which requires signaling via Calmodulin binding motif in the C0 domain of the NMDAR GluN1 subunit. Interestingly, in neurons lacking NMDARs, whereas GABAergic synaptic transmission is strongly reduced, the tonic inhibition mediated by extrasynaptic GABAA receptors is increased, suggesting a compensatory mechanism for the lack of synaptic inhibition. These results demonstrate a crucial role for NMDARs in specifying the development of inhibitory synapses, and suggest an important mechanism for controlling the establishment of the balance between synaptic excitation and inhibition in the developing brain.

  5. Romantic love is associated with enhanced inhibitory control in an emotional stop-signal task

    Directory of Open Access Journals (Sweden)

    Sensen Song

    2016-10-01

    Full Text Available Purpose: This study explored whether romantic lovers differ in emotion-related inhibitory control capacity from those who are single. Methods: 88 healthy undergraduate college students participated in the study. Half were currently in love and in a romantic relationship (love group, LG, and half were single and had never been in a romantic relationship (single group, SG. Based on duration of romantic relationship (i.e., love duration, the LG were further divided into two subgroups: early stage love and longer periods of love. All participants completed an emotional Stop Signal Task (eSST, which consisted of a variety of human face stimuli representing sadness (a negative emotion, as well as neutral emotions. Results: Results found that relative to SG, lovers showed greater inhibitory control [shorter stop-signal reaction time (SSRT] during negative emotion condition trials. Furthermore, in early stages of love, SSRT for negative emotion condition trials was significantly shorter compared to that in longer periods of love or SG individuals, with no significant differences between the latter two groups. Conclusions: Compared with individuals who were single, early-stage lovers showed greater capacity for inhibiting action during presentation of negative emotional stimuli. Within a greater social context, greater inhibitory control capacity during early stages of love may be related to the successful formation of romantic relationships, particularly to the ability to persevere in goal-directed action despite negative emotional contexts such as that of sadness.

  6. Romantic Love Is Associated with Enhanced Inhibitory Control in an Emotional Stop-Signal Task

    Science.gov (United States)

    Song, Sensen; Zou, Zhiling; Song, Hongwen; Wang, Yongming; d’Oleire Uquillas, Federico; Wang, Huijun; Chen, Hong

    2016-01-01

    Purpose: This study explored whether romantic lovers differ in emotion-related inhibitory control capacity from those who are single. Methods: 88 healthy undergraduate college students participated in the study. Half were currently in love and in a romantic relationship (love group, LG), and half were single and had never been in a romantic relationship (single group, SG). Based on duration of romantic relationship (i.e., love duration), the LG were further divided into two subgroups: “early stage love” and “longer periods of love”. All participants completed an emotional Stop Signal Task, consisting of a variety of human face stimuli displaying either sad or neutral affect. Results: Results found that relative to SG, lovers showed greater inhibitory control [shorter stop-signal reaction time (SSRT)] during negative emotion condition trials. Furthermore, in early stages of love, SSRT for negative emotion condition trials was significantly shorter compared to that in “longer periods of love” or SG individuals, with no significant differences between the two latter groups. Conclusion: Compared with individuals who were single, early stage lovers showed greater capacity for inhibiting action during presentation of negative emotional stimuli. Within a greater social context, greater inhibitory control capacity during early stages of love may be related to the successful formation of romantic relationships, particularly to the ability to persevere in goal-directed action despite negative emotional contexts such as that of sadness. PMID:27826260

  7. [Chemical Constituents from Leaves of Hibiscus syriacus and Their α-Glucosidase Inhibitory Activities].

    Science.gov (United States)

    Wei, Qiang; Ji, Xiao-ying; Xu, Fei; Li, Qian-rong; Yin, Hao

    2015-05-01

    To study the chemical constituents from Hibiscus syriacus leaves and their α-glucosidase inhibitory activities. Column chromatography including macroporous resins, silica gel and Sephadex LH-20 were used for the isolation and purification of all compounds. Spectroscopic methods including physical and chemical properties, 1H-NMR and 13C-NMR were used for the identification of structures. Their α-glucosidase inhibitory activities were detected by a 96-well microplate. 15 compounds were isolated and identified as β-sitosterol(1), β-daucostero (2), β-amyrin (3), oleanolic acid (4), stigmast-4-en-3-one (5), friedelin (6), syriacusin A (7), kaempferol (8), isovitexin (9), vitexin (10), apigenin (11), apigenin-7-O-β-D-glucopyranoside (12), luteolin-7-O-β-D-glucopyranoside (13), vitexin-7-O-β-D-glucopyranoside (14) and rutin (15). All the compounds are isolated from the leaves of Hibiscus syriacus for the first time. Taking acarbose as positive control, the α-glucosidase inhibitory activities of 15 compounds were evaluated. Compounds 7 and 9 have shown strong α-glucosidase inhibitory activities with IC50 of 39.03 ± 0.38 and 32.12 ± 0.62 mg/L, inhibition ratio of 94.95% and 97.15%, respectively.

  8. A Journey through the Gonadotropin-Inhibitory Hormone System of Fish

    Directory of Open Access Journals (Sweden)

    José A. Muñoz-Cueto

    2017-10-01

    Full Text Available Gonadotropin-inhibitory hormone (GnIH is a hypothalamic neuropeptide that belongs to the RFamide peptide family and was first identified in the quail brain. From the discovery of avian GnIH, orthologous GnIH peptides have been reported in a variety of vertebrates, including mammals, amphibians, teleosts and agnathans, but also in protochordates. It has been clearly established that GnIH suppresses reproduction in avian and mammalian species through its inhibitory actions on brain GnRH and pituitary gonadotropins. In addition, GnIH also appears to be involved in the regulation of feeding, growth, stress response, heart function and social behavior. These actions are mediated via G protein-coupled GnIH receptors (GnIH-Rs, of which two different subtypes, GPR147 and GPR74, have been described to date. With around 30,000 species, fish represent more than one-half of the total number of recognized living vertebrate species. In addition to this impressive biological diversity, fish are relevant because they include model species with scientific and clinical interest as well as many exploited species with economic importance. In spite of this, the study of GnIH and its physiological effects on reproduction and other physiological processes has only been approached in a few fish species, and results obtained are in some cases conflicting. In this review, we summarize the information available in the literature on GnIH sequences identified in fish, the distribution of GnIH and GnIH-Rs in central and peripheral tissues, the physiological actions of GnIH on the reproductive brain-pituitary-gonadal axis, as well as other reported effects of this neuropeptide, and existing knowledge on the regulatory mechanisms of GnIH in fish.

  9. Inhibitory actions by ibandronate sodium, a nitrogen-containing bisphosphonate, on calcium-activated potassium channels in Madin–Darby canine kidney cells

    Directory of Open Access Journals (Sweden)

    Sheng-Nan Wu

    2015-01-01

    Full Text Available The nitrogen-containing bisphosphonates used for management of the patients with osteoporosis were reported to influence the function of renal tubular cells. However, how nitrogen-containing bisphosphates exert any effects on ion currents remains controversial. The effects of ibandronate (Iban, a nitrogen-containing bisphosphonate, on ionic channels, including two types of Ca2+-activated K+ (KCa channels, namely, large-conductance KCa (BKCa and intermediate-conductance KCa (IKCa channels, were investigated in Madin–Darby canine kidney (MDCK cells. In whole-cell current recordings, Iban suppressed the amplitude of voltage-gated K+ current elicited by long ramp pulse. Addition of Iban caused a reduction of BKCa channels accompanied by a right shift in the activation curve of BKCa channels, despite no change in single-channel conductance. Ca2+ sensitivity of these channels was modified in the presence of this compound; however, the magnitude of Iban-mediated decrease in BKCa-channel activity under membrane stretch with different negative pressure remained unchanged. Iban suppressed the probability of BKCa-channel openings linked primarily to a shortening in the slow component of mean open time in these channels. The dissociation constant needed for Iban-mediated suppression of mean open time in MDCK cells was 12.2 μM. Additionally, cell exposure to Iban suppressed the activity of IKCa channels, and DC-EBIO or 9-phenanthrol effectively reversed its suppression. Under current-clamp configuration, Iban depolarized the cells and DC-EBIO or PF573228 reversed its depolarizing effect. Taken together, the inhibitory action of Iban on KCa-channel activity may contribute to the underlying mechanism of pharmacological or toxicological actions of Iban and its structurally similar bisphosphonates on renal tubular cells occurring in vivo.

  10. Purification of a Novel Bacteriocin-Like Inhibitory Substance Produced by Enterococcus faecium ICIS 8 and Characterization of Its Mode of Action.

    Science.gov (United States)

    Vasilchenko, Alexey S; Rogozhin, Eugene A; Valyshev, Alexander V

    2017-06-01

    The aim of this work was to purify and characterize a bacteriocin-like antimicrobial substance produced by an antagonistic active strain of Enterococcus faecium. A novel bacteriocin-like inhibitory substance (BLIS) produced by the E. faecium ICIS 8 strain was purified and characterized using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and N-terminal amino acid sequencing revealed the following partial sequence: NH 2 -APKEKCFPKYCV. The proteinaceous nature of purified BLIS was assessed by treatment with proteolytic enzyme. Studies of the action of BLIS using bacteriological and bioluminescence assays revealed a dose-dependent inhibition of Listeria monocytogenes 88BK and Escherichia coli K12 TG1 lac::lux viability. The interaction of the BLIS with the bacterial surface led to the compensation of a negative charge value, as shown by zeta-potential measurements. Assessments of membrane integrity using fluorescent probes and atomic force microscopy revealed the permeabilization of the cellular barrier structures in both L. monocytogenes and E. coli. The novel BLIS from E. faecium ICIS 8 was characterized by a unique primary peptide sequence and exerted bactericidal activity against L. monocytogenes and E. coli by disrupting membrane integrity.

  11. [Substrate-inhibitory analysis of monoamine oxidase from hepatopancreas of the octopus Bathypolypus arcticus].

    Science.gov (United States)

    Basova, I N; Iagodina, O V

    2012-01-01

    Study of the substrate-inhibitory specificity of mitochondrial monoamine oxidase (MAO) of hepatopancreas of the octopus Bathypolypus arcticus revealed distinctive peculiarities of catalytic properties of this enzyme. The studied enzyme, on one hand, like the classic MAO of homoiothermal animals, is able to deaminate tyramine, serotonin, benzylamine, tryptamine, beta-phenylethylamine, while, on the other hand, deaminates histamine and does not deaminate putrescine--classic substrates of diamine oxidase (DAO). Results of the substrate-inhibitory analysis with use of chlorgiline and deprenyl are indirect proofs of the existence in the octopus hepatopancreas of one molecular MAO form. Semicarbazide and pyronine G turned out to be weak irreversible inhibitors, four derivatives of acridine--irreversible inhibitors of the intermediate effectiveness with respect to the octopus hepatopancreas MAO; specificity of action of inhibitors at deamination of different substrates was equal.

  12. Mechanisms underlying electrical and mechanical responses of the bovine retractor penis to inhibitory nerve stimulation and to an inhibitory extract.

    Science.gov (United States)

    Byrne, N. G.; Muir, T. C.

    1985-01-01

    The response of the bovine retractor penis (BRP) to stimulation of non-adrenergic, non-cholinergic (NANC) inhibitory nerves and to an inhibitory extract prepared from this muscle have been studied using intracellular microelectrode, sucrose gap and conventional mechanical recording techniques. Both inhibitory nerve stimulation and inhibitory extract hyperpolarized the membrane potential and relaxed spontaneous or guanethidine (3 X 10(-5) M)-induced tone. These effects were accompanied by an increase in membrane resistance. Following membrane potential displacement from an average value of -53 +/- 7 mV (n = 184; Byrne & Muir, 1984) inhibitory potentials to nerve stimulation were abolished at approximately -30 mV; there was no evidence of reversal. Displacement by inward hyperpolarizing current over the range -45 to -60 mV increased the inhibitory response to nerve stimulation and to inhibitory extract; at more negative potential values (above approximately -60 mV) the inhibitory potential decreased and was abolished (approximately -103 mV). There was no evidence of reversal. Removal of [K+]o reversibly reduced hyperpolarization to nerve stimulation and inhibitory extract. No enhancement was observed. Increasing the [K+]o to 20 mM reduced the inhibitory potential to nerve stimulation but this was restored by passive membrane hyperpolarization. Inhibitory potentials were obtained at membrane potential values exceeding that of the estimated EK (-49 mV). [Cl-]o-free or [Cl-]o-deficient solutions reduced and abolished (after some 20-25 min) the hyperpolarization produced by inhibitory nerve stimulation or inhibitory extract. The inhibitory potential amplitude following nerve stimulation was not restored by passive displacement of the membrane potential from -26 to -104 mV approximately. Ouabain (1-5 X 10(-5) M) reduced then (45-60 min later) abolished the inhibitory potential to nerve stimulation. The effects of this drug on the extract were not investigated. It is

  13. Inhibitory effect of propolis on the development of AA amyloidosis.

    Science.gov (United States)

    Harata, Daichi; Tsuchiya, Yuya; Miyoshi, Tomoyuki; Yanai, Tokuma; Suzuki, Kazuhiko; Murakami, Tomoaki

    2018-04-01

    In the several types of amyloidoses, participation of oxidative stresses in the pathogenesis and the effect of antioxidants on amyloidosis have been reported. Meanwhile, the relationship between oxidative stresses and pathogenesis of amyloid A (AA) amyloidosis is still unclear. In this study, we used an antioxidant, Brazilian propolis, to investigate the inhibitory effects on AA amyloidosis. The results showed that AA deposition was inhibited by administration of propolis. Increased expression of antioxidant markers was detected in molecular biological examinations of mice treated with propolis. Although serum amyloid A (SAA) levels were strongly correlated with the immunoreactive area of AA deposits in the control group, the correlation was weaker in the propolis-treated groups. In addition, there were no changes in SAA levels between the control group and the propolis-treated groups. The results indicate that propolis, an antioxidant, may induce inhibitory effects against AA amyloidosis.

  14. Inhibitory neuron and hippocampal circuit dysfunction in an aged mouse model of Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Anupam Hazra

    Full Text Available In Alzheimer's disease (AD, a decline in explicit memory is one of the earliest signs of disease and is associated with hippocampal dysfunction. Amyloid protein exerts a disruptive impact on neuronal function, but the specific effects on hippocampal network activity are not well known. In this study, fast voltage-sensitive dye imaging and extracellular and whole-cell electrophysiology were used on entorhinal cortical-hippocampal slice preparations to characterize hippocampal network activity in 12-16 month old female APPswe/PSEN1DeltaE9 (APdE9 mice mice. Aged APdE9 mice exhibited profound disruptions in dentate gyrus circuit activation. High frequency stimulation of the perforant pathway in the dentate gyrus (DG area of APdE9 mouse tissue evoked abnormally large field potential responses corresponding to the wider neural activation maps. Whole-cell patch clamp recordings of the identified inhibitory interneurons in the molecular layer of DG revealed that they fail to reliably fire action potentials. Taken together, abnormal DG excitability and an inhibitory neuron failure to generate action potentials are suggested to be important contributors to the underlying cellular mechanisms of early-stage Alzheimer's disease pathophysiology.

  15. Dynamics of Time Delay-Induced Multiple Synchronous Behaviors in Inhibitory Coupled Neurons

    Science.gov (United States)

    Gu, Huaguang; Zhao, Zhiguo

    2015-01-01

    The inhibitory synapse can induce synchronous behaviors different from the anti-phase synchronous behaviors, which have been reported in recent studies. In the present paper, synchronous behaviors are investigated in the motif model composed of reciprocal inhibitory coupled neurons with endogenous bursting and time delay. When coupling strength is weak, synchronous behavior appears at a single interval of time delay within a bursting period. When coupling strength is strong, multiple synchronous behaviors appear at different intervals of time delay within a bursting period. The different bursting patterns of synchronous behaviors, and time delays and coupling strengths that can induce the synchronous bursting patterns can be well interpreted by the dynamics of the endogenous bursting pattern of isolated neuron, which is acquired by the fast-slow dissection method, combined with the inhibitory coupling current. For an isolated neuron, when a negative impulsive current with suitable strength is applied at different phases of the bursting, multiple different bursting patterns can be induced. For a neuron in the motif, the inhibitory coupling current, of which the application time and strength is modulated by time delay and coupling strength, can cause single or multiple synchronous firing patterns like the negative impulsive current when time delay and coupling strength is suitable. The difference compared to the previously reported multiple synchronous behaviors that appear at time delays wider than a period of the endogenous firing is discussed. The results present novel examples of synchronous behaviors in the neuronal network with inhibitory synapses and provide a reasonable explanation. PMID:26394224

  16. Synchronisation hubs in the visual cortex may arise from strong rhythmic inhibition during gamma oscillations.

    Science.gov (United States)

    Folias, Stefanos E; Yu, Shan; Snyder, Abigail; Nikolić, Danko; Rubin, Jonathan E

    2013-09-01

    Neurons in the visual cortex exhibit heterogeneity in feature selectivity and the tendency to generate action potentials synchronously with other nearby neurons. By examining visual responses from cat area 17 we found that, during gamma oscillations, there was a positive correlation between each unit's sharpness of orientation tuning, strength of oscillations, and propensity towards synchronisation with other units. Using a computational model, we demonstrated that heterogeneity in the strength of rhythmic inhibitory inputs can account for the correlations between these three properties. Neurons subject to strong inhibition tend to oscillate strongly in response to both optimal and suboptimal stimuli and synchronise promiscuously with other neurons, even if they have different orientation preferences. Moreover, these strongly inhibited neurons can exhibit sharp orientation selectivity provided that the inhibition they receive is broadly tuned relative to their excitatory inputs. These results predict that the strength and orientation tuning of synaptic inhibition are heterogeneous across area 17 neurons, which could have important implications for these neurons' sensory processing capabilities. Furthermore, although our experimental recordings were conducted in the visual cortex, our model and simulation results can apply more generally to any brain region with analogous neuron types in which heterogeneity in the strength of rhythmic inhibition can arise during gamma oscillations. © 2013 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  17. A deleterious Nav1.1 mutation selectively impairs telencephalic inhibitory neurons derived from Dravet Syndrome patients

    Science.gov (United States)

    Sun, Yishan; Paşca, Sergiu P; Portmann, Thomas; Goold, Carleton; Worringer, Kathleen A; Guan, Wendy; Chan, Karen C; Gai, Hui; Vogt, Daniel; Chen, Ying-Jiun J; Mao, Rong; Chan, Karrie; Rubenstein, John LR; Madison, Daniel V; Hallmayer, Joachim; Froehlich-Santino, Wendy M; Bernstein, Jonathan A; Dolmetsch, Ricardo E

    2016-01-01

    Dravet Syndrome is an intractable form of childhood epilepsy associated with deleterious mutations in SCN1A, the gene encoding neuronal sodium channel Nav1.1. Earlier studies using human induced pluripotent stem cells (iPSCs) have produced mixed results regarding the importance of Nav1.1 in human inhibitory versus excitatory neurons. We studied a Nav1.1 mutation (p.S1328P) identified in a pair of twins with Dravet Syndrome and generated iPSC-derived neurons from these patients. Characterization of the mutant channel revealed a decrease in current amplitude and hypersensitivity to steady-state inactivation. We then differentiated Dravet-Syndrome and control iPSCs into telencephalic excitatory neurons or medial ganglionic eminence (MGE)-like inhibitory neurons. Dravet inhibitory neurons showed deficits in sodium currents and action potential firing, which were rescued by a Nav1.1 transgene, whereas Dravet excitatory neurons were normal. Our study identifies biophysical impairments underlying a deleterious Nav1.1 mutation and supports the hypothesis that Dravet Syndrome arises from defective inhibitory neurons. DOI: http://dx.doi.org/10.7554/eLife.13073.001 PMID:27458797

  18. Soluble epoxide hydrolase inhibitory activity of anthraquinone components from Aloe.

    Science.gov (United States)

    Sun, Ya Nan; Kim, Jang Hoon; Li, Wei; Jo, A Reum; Yan, Xi Tao; Yang, Seo Young; Kim, Young Ho

    2015-10-15

    Aloe is a short-stemmed succulent herb widely used in traditional medicine to treat various diseases and as raw material in cosmetics and heath foods. In this study, we isolated and identified two new anthraquinone derivatives, aloinoside C (6) and aloinoside D (7), together with six known compounds from an aqueous dissolved Aloe exudate. Their structures were identified by spectroscopic analysis. The inhibitory effects of the isolated compounds on soluble epoxide hydrolase (sEH) were evaluated. Compounds 1-8 inhibited sEH activity potently, with IC50 values ranging from 4.1±0.6 to 41.1±4.2 μM. A kinetic analysis of compounds 1-8 revealed that the inhibitory actions of compounds 1, 6 and 8 were non-competitive, whereas those of compounds 2-5 and 7 were the mixed-type. Molecular docking increases our understanding of receptor-ligand binding of all compounds. These results demonstrate that compounds 1-8 from Aloe are potential sEH inhibitors. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Inhibitory effect of artocarpanone from Artocarpus heterophyllus on melanin biosynthesis.

    Science.gov (United States)

    Arung, Enos Tangke; Shimizu, Kuniyoshi; Kondo, Ryuichiro

    2006-09-01

    In our previous efforts to find new tyrosinase inhibitory materials, we investigated 44 Indonesian medicinal plants belonging to 24 families. Among those plants, the extract of Artocarpus heterophyllus was one of the strongest inhibitors of tyrosinase activity. By activity-guided fractionation of A. heterophyllus wood extract, we isolated artocarpanone, which inhibited both mushroom tyrosinase activity and melanin production in B16 melanoma cells. This compound is a strong candidate as a remedy for hyperpigmentation in human skin.

  20. When is an Inhibitory Synapse Effective?

    Science.gov (United States)

    Qian, Ning; Sejnowski, Terrence J.

    1990-10-01

    Interactions between excitatory and inhibitory synaptic inputs on dendrites determine the level of activity in neurons. Models based on the cable equation predict that silent shunting inhibition can strongly veto the effect of an excitatory input. The cable model assumes that ionic concentrations do not change during the electrical activity, which may not be a valid assumption, especially for small structures such as dendritic spines. We present here an analysis and computer simulations to show that for large Cl^- conductance changes, the more general Nernst-Planck electrodiffusion model predicts that shunting inhibition on spines should be much less effective than that predicted by the cable model. This is a consequence of the large changes in the intracellular ionic concentration of Cl^- that can occur in small structures, which would alter the reversal potential and reduce the driving force for Cl^-. Shunting inhibition should therefore not be effective on spines, but it could be significantly more effective on the dendritic shaft at the base of the spine. In contrast to shunting inhibition, hyperpolarizing synaptic inhibition mediated by K^+ currents can be very effective in reducing the excitatory synaptic potentials on the same spine if the excitatory conductance change is less than 10 nS. We predict that if the inhibitory synapses found on cortical spines are to be effective, then they should be mediated by K^+ through GABA_B receptors.

  1. Do Children with Better Inhibitory Control Donate More? Differentiating between Early and Middle Childhood and Cool and Hot Inhibitory Control

    Directory of Open Access Journals (Sweden)

    Jian Hao

    2017-12-01

    Full Text Available Inhibitory control may play an important part in prosocial behavior, such as donating behavior. However, it is not clear at what developmental stage inhibitory control becomes associated with donating behavior and which aspects of inhibitory control are related to donating behavior during development in early to middle childhood. The present study aimed to clarify these issues with two experiments. In Experiment 1, 103 3- to 5-year-old preschoolers completed cool (Stroop-like and hot (delay of gratification inhibitory control tasks and a donating task. The results indicated that there were no relationships between cool or hot inhibitory control and donating behavior in the whole group and each age group of the preschoolers. In Experiment 2, 140 elementary school children in Grades 2, 4, and 6 completed cool (Stroop-like and hot (delay of gratification inhibitory control tasks and a donating task. The results showed that inhibitory control was positively associated with donating behavior in the whole group. Cool and hot inhibitory control respectively predicted donating behavior in the second and sixth graders. Therefore, the present study reveals that donating behavior increasingly relies on specific inhibitory control, i.e., hot inhibitory control as children grow in middle childhood.

  2. Direction-selective circuitry in rat retina develops independently of GABAergic, cholinergic and action potential activity.

    Directory of Open Access Journals (Sweden)

    Le Sun

    Full Text Available The ON-OFF direction selective ganglion cells (DSGCs in the mammalian retina code image motion by responding much more strongly to movement in one direction. They do so by receiving inhibitory inputs selectively from a particular sector of processes of the overlapping starburst amacrine cells, a type of retinal interneuron. The mechanisms of establishment and regulation of this selective connection are unknown. Here, we report that in the rat retina, the morphology, physiology of the ON-OFF DSGCs and the circuitry for coding motion directions develop normally with pharmacological blockade of GABAergic, cholinergic activity and/or action potentials for over two weeks from birth. With recent results demonstrating light independent formation of the retinal DS circuitry, our results strongly suggest the formation of the circuitry, i.e., the connections between the second and third order neurons in the visual system, can be genetically programmed, although emergence of direction selectivity in the visual cortex appears to require visual experience.

  3. Effects of Neuromodulation on Excitatory-Inhibitory Neural Network Dynamics Depend on Network Connectivity Structure

    Science.gov (United States)

    Rich, Scott; Zochowski, Michal; Booth, Victoria

    2018-01-01

    Acetylcholine (ACh), one of the brain's most potent neuromodulators, can affect intrinsic neuron properties through blockade of an M-type potassium current. The effect of ACh on excitatory and inhibitory cells with this potassium channel modulates their membrane excitability, which in turn affects their tendency to synchronize in networks. Here, we study the resulting changes in dynamics in networks with inter-connected excitatory and inhibitory populations (E-I networks), which are ubiquitous in the brain. Utilizing biophysical models of E-I networks, we analyze how the network connectivity structure in terms of synaptic connectivity alters the influence of ACh on the generation of synchronous excitatory bursting. We investigate networks containing all combinations of excitatory and inhibitory cells with high (Type I properties) or low (Type II properties) modulatory tone. To vary network connectivity structure, we focus on the effects of the strengths of inter-connections between excitatory and inhibitory cells (E-I synapses and I-E synapses), and the strengths of intra-connections among excitatory cells (E-E synapses) and among inhibitory cells (I-I synapses). We show that the presence of ACh may or may not affect the generation of network synchrony depending on the network connectivity. Specifically, strong network inter-connectivity induces synchronous excitatory bursting regardless of the cellular propensity for synchronization, which aligns with predictions of the PING model. However, when a network's intra-connectivity dominates its inter-connectivity, the propensity for synchrony of either inhibitory or excitatory cells can determine the generation of network-wide bursting.

  4. Inhibitory effects of tiamulin on contractile and electrical responses in isolated thoracic aorta and cardiac muscle of guinea-pigs.

    Science.gov (United States)

    Nakajyo, S; Hara, Y; Hirano, S; Agata, N; Shimizu, K; Urakawa, N

    1992-09-01

    The inhibitory effect of tiamulin, an antibiotic produced by Pleurotus mutilis, on contractile and electrical responses in isolated thoracic aorta and cardiac muscle of guinea-pigs was studied. In the thoracic aorta, tiamulin with an IC50 of 9.7 x 10(-6) M inhibited sustained contractions induced by isosmotically added 60 mM KCl. The inhibitory effect of tiamulin on a Ca(2+)-induced contraction in a depolarized muscle was competitively antagonized by raising external Ca2+ concentration. Bay K 8644 (10(-7) M) antagonized tiamulin's inhibition of the Ca(2+)-induced contraction. Tiamulin (2 x 10(-5) M) decreased the elevated cytoplasmic Ca2+ level measured by the fura 2 AM method in the depolarized muscle. In high K(+)-isoprenaline-treated left atria, tiamulin (2 x 10(-5)-2 x 10(-4) M) produced negative inotropic effects. On the other hand in the membrane action potential of papillary muscles, tiamulin (2 x 10(-6)-2 x 10(-4) M) produced decreases in action potential and durations and 2 x 10(-4) M tiamulin depressed the slow response action potential in depolarized muscles. Tiamulin produced prolongations of the PR interval in ECG, negative chrono- and inotropic effects, and an increase in perfusion flow in guinea-pig isolated and perfused hearts. These effects of tiamulin on the aorta or cardiac muscle were similar to those of verapamil and nifedipine. These results suggest that both the inhibitory action of tiamulin on the high K(+)-induced contraction in the aorta and the negative inotropic effect of tiamulin on the cardiac muscle are due to an inhibition of Ca2+ entry through the voltage-dependent Ca2+ channels of cells of both these muscles.

  5. Provocative and inhibitory effects of a video-EEG neuropsychologic protocol in juvenile myoclonic epilepsy.

    Science.gov (United States)

    Guaranha, Mirian Salvadori Bittar; da Silva Sousa, Patrícia; de Araújo-Filho, Gerardo Maria; Lin, Katia; Guilhoto, Laura Maria Figueiredo Ferreira; Caboclo, Luís Otávio Sales Ferreira; Yacubian, Elza Márcia Targas

    2009-11-01

    Studies suggest that higher cognitive functions could precipitate seizures in juvenile myoclonic epilepsy (JME). The present study aimed to analyze the effects of higher mental activity on epileptiform discharges and seizures in patients with JME and compare them to those of habitual methods of activation. Seventy-six patients with JME (41 female) underwent a video-EEG (electroencephalography) neuropsychologic protocol (VNPP) and habitual methods of activation for 4-6 h. Twenty-nine of the 76 (38.2%) presented provocative effect, and inhibition was seen in 28 of 31 (90.3%). A mixed effect was observed in 11 (35.5%), and 30 patients (39.5%) suffered no effect of VNPP. Action-programming tasks were more effective than thinking in provoking epileptiform discharges (23.7% and 11.0% of patients, respectively, p = 0.03). Inhibitory effect was observed equally in the various categories of tasks, except in mental calculation, which had a higher inhibitory rate. Habitual methods of activation were more effective than VNPP in provoking discharges. Anxiety disorders were diagnosed in 24 of 58 patients (41.4%); anxious patients had greater discharge indexes and no significant inhibitory effect on VNPP. Praxis exerted the most remarkable provocative effect, in accordance with the motor circuitry hyperexcitability hypothesis in JME. Inhibitory effect, which had no such task specificity, might be mediated by a widespread cortical-thalamic pathway, possibly involving the parietal cortex. The frequent inhibitory effect found under cortical activation conditions, influenced by the presence of anxiety, supports nonpharmacologic therapeutic interventions in JME.

  6. Dipeptidyl peptidase-IV inhibitory activity of dimeric dihydrochalcone glycosides from flowers of Helichrysum arenarium.

    Science.gov (United States)

    Morikawa, Toshio; Ninomiya, Kiyofumi; Akaki, Junji; Kakihara, Namiko; Kuramoto, Hiroyuki; Matsumoto, Yurie; Hayakawa, Takao; Muraoka, Osamu; Wang, Li-Bo; Wu, Li-Jun; Nakamura, Seikou; Yoshikawa, Masayuki; Matsuda, Hisashi

    2015-10-01

    A methanol extract of everlasting flowers of Helichrysum arenarium L. Moench (Asteraceae) was found to inhibit the increase in blood glucose elevation in sucrose-loaded mice at 500 mg/kg p.o. The methanol extract also inhibited the enzymatic activity against dipeptidyl peptidase-IV (DPP-IV, IC50 = 41.2 μg/ml), but did not show intestinal α-glucosidase inhibitory activities. From the extract, three new dimeric dihydrochalcone glycosides, arenariumosides V-VII (2-4), were isolated, and the stereostructures were elucidated based on their spectroscopic properties and chemical evidence. Of the constituents, several flavonoid constituents, including 2-4, were isolated, and these isolated constituents were investigated for their DPP-IV inhibitory effects. Among them, chalconaringenin 2'-O-β-D-glucopyranoside (16, IC50 = 23.1 μM) and aureusidin 6-O-β-D-glucopyranoside (35, 24.3 μM) showed relatively strong inhibitory activities.

  7. Lanostane triterpenes from the mushroom Ganoderma resinaceum and their inhibitory activities against α-glucosidase.

    Science.gov (United States)

    Chen, Xian-Qiang; Zhao, Jing; Chen, Ling-Xiao; Wang, Shen-Fei; Wang, Ying; Li, Shao-Ping

    2018-05-01

    Eighteen previously undescribed lanostane triterpenes and thirty known analogues were obtained from the fruiting bodies of Ganoderma resinaceum. Resinacein C was isolated from a natural source for the first time. The structures of all the above compounds were elucidated by extensive spectroscopic analysis and comparisons of their spectroscopic data with those reported in the literature. Furthermore, in an in vitro assay, Resinacein C, ganoderic acid Y, lucialdehyde C, 7-oxo-ganoderic acid Z 3 , 7-oxo-ganoderic acid Z, and lucidadiol showed strong inhibitory effects against α-glucosidase compared with the positive control drug acarbose. The structure-activity relationships of ganoderma triterpenes on α-glucosidase inhibition showed that the C-24/C-25 double bond is necessary for α-glucosidase inhibitory activity. Moreover, the carboxylic acid group at C-26 and the hydroxy group at C-15 play important roles in enhancing inhibitory effects of these triterpenes. Copyright © 2018. Published by Elsevier Ltd.

  8. Dexmedetomidine decreases inhibitory but not excitatory neurotransmission to cardiac vagal neurons in the nucleus ambiguus.

    Science.gov (United States)

    Sharp, Douglas B; Wang, Xin; Mendelowitz, David

    2014-07-29

    Dexmedetomidine, an α2 adrenergic agonist, is a useful sedative but can also cause significant bradycardia. This decrease in heart rate may be due to decreased central sympathetic output as well as increased parasympathetic output from brainstem cardiac vagal neurons. In this study, using whole cell voltage clamp methodology, the actions of dexmedetomidine on excitatory glutamatergic and inhibitory GABAergic and glycinergic neurotransmission to parasympathetic cardiac vagal neurons in the rat nucleus ambiguus was determined. The results indicate that dexmedetomidine decreases both GABAergic and glycinergic inhibitory input to cardiac vagal neurons, with no significant effect on excitatory input. These results provide a mechanism for dexmedetomidine induced bradycardia and has implications for the management of this potentially harmful side effect. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. Inhibitory Activity of (+-Usnic Acid against Non-Small Cell Lung Cancer Cell Motility.

    Directory of Open Access Journals (Sweden)

    Yi Yang

    Full Text Available Lichens are symbiotic organisms that produce various unique chemicals that can be used for pharmaceutical purposes. With the aim of screening new anti-cancer agents that inhibit cancer cell motility, we tested the inhibitory activity of seven lichen species collected from the Romanian Carpathian Mountains against migration and invasion of human lung cancer cells and further investigated the molecular mechanisms underlying their anti-metastatic activity. Among them, Alectoria samentosa, Flavocetraria nivalis, Alectoria ochroleuca, and Usnea florida showed significant inhibitory activity against motility of human lung cancer cells. HPLC results showed that usnic acid is the main compound in these lichens, and (+-usnic acid showed similar inhibitory activity that crude extract have. Mechanistically, β-catenin-mediated TOPFLASH activity and KITENIN-mediated AP-1 activity were decreased by (+-usnic acid treatment in a dose-dependent manner. The quantitative real-time PCR data showed that (+-usnic acid decreased the mRNA level of CD44, Cyclin D1 and c-myc, which are the downstream target genes of both β-catenin/LEF and c-jun/AP-1. Also, Rac1 and RhoA activities were decreased by treatment with (+-usnic acid. Interestingly, higher inhibitory activity for cell invasion was observed when cells were treated with (+-usnic acid and cetuximab. These results implied that (+-usnic acid might have potential activity in inhibition of cancer cell metastasis, and (+-usnic acid could be used for anti-cancer therapy with a distinct mechanisms of action.

  10. Inhibitory Activity of (+)-Usnic Acid against Non-Small Cell Lung Cancer Cell Motility

    Science.gov (United States)

    Yang, Yi; Nguyen, Thanh Thi; Jeong, Min-Hye; Crişan, Florin; Yu, Young Hyun; Ha, Hyung-Ho; Choi, Kyung Hee; Jeong, Hye Gwang; Jeong, Tae Cheon; Lee, Kwang Youl; Kim, Kyung Keun; Hur, Jae-Seoun; Kim, Hangun

    2016-01-01

    Lichens are symbiotic organisms that produce various unique chemicals that can be used for pharmaceutical purposes. With the aim of screening new anti-cancer agents that inhibit cancer cell motility, we tested the inhibitory activity of seven lichen species collected from the Romanian Carpathian Mountains against migration and invasion of human lung cancer cells and further investigated the molecular mechanisms underlying their anti-metastatic activity. Among them, Alectoria samentosa, Flavocetraria nivalis, Alectoria ochroleuca, and Usnea florida showed significant inhibitory activity against motility of human lung cancer cells. HPLC results showed that usnic acid is the main compound in these lichens, and (+)-usnic acid showed similar inhibitory activity that crude extract have. Mechanistically, β-catenin-mediated TOPFLASH activity and KITENIN-mediated AP-1 activity were decreased by (+)-usnic acid treatment in a dose-dependent manner. The quantitative real-time PCR data showed that (+)-usnic acid decreased the mRNA level of CD44, Cyclin D1 and c-myc, which are the downstream target genes of both β-catenin/LEF and c-jun/AP-1. Also, Rac1 and RhoA activities were decreased by treatment with (+)-usnic acid. Interestingly, higher inhibitory activity for cell invasion was observed when cells were treated with (+)-usnic acid and cetuximab. These results implied that (+)-usnic acid might have potential activity in inhibition of cancer cell metastasis, and (+)-usnic acid could be used for anti-cancer therapy with a distinct mechanisms of action. PMID:26751081

  11. Strong Coupling Holography

    CERN Document Server

    Dvali, Gia

    2009-01-01

    We show that whenever a 4-dimensional theory with N particle species emerges as a consistent low energy description of a 3-brane embedded in an asymptotically-flat (4+d)-dimensional space, the holographic scale of high-dimensional gravity sets the strong coupling scale of the 4D theory. This connection persists in the limit in which gravity can be consistently decoupled. We demonstrate this effect for orbifold planes, as well as for the solitonic branes and string theoretic D-branes. In all cases the emergence of a 4D strong coupling scale from bulk holography is a persistent phenomenon. The effect turns out to be insensitive even to such extreme deformations of the brane action that seemingly shield 4D theory from the bulk gravity effects. A well understood example of such deformation is given by large 4D Einstein term in the 3-brane action, which is known to suppress the strength of 5D gravity at short distances and change the 5D Newton's law into the four-dimensional one. Nevertheless, we observe that the ...

  12. Plasticity of cortical excitatory-inhibitory balance.

    Science.gov (United States)

    Froemke, Robert C

    2015-07-08

    Synapses are highly plastic and are modified by changes in patterns of neural activity or sensory experience. Plasticity of cortical excitatory synapses is thought to be important for learning and memory, leading to alterations in sensory representations and cognitive maps. However, these changes must be coordinated across other synapses within local circuits to preserve neural coding schemes and the organization of excitatory and inhibitory inputs, i.e., excitatory-inhibitory balance. Recent studies indicate that inhibitory synapses are also plastic and are controlled directly by a large number of neuromodulators, particularly during episodes of learning. Many modulators transiently alter excitatory-inhibitory balance by decreasing inhibition, and thus disinhibition has emerged as a major mechanism by which neuromodulation might enable long-term synaptic modifications naturally. This review examines the relationships between neuromodulation and synaptic plasticity, focusing on the induction of long-term changes that collectively enhance cortical excitatory-inhibitory balance for improving perception and behavior.

  13. Antioxidative Characteristics of Anisomeles indica Extract and Inhibitory Effect of Ovatodiolide on Melanogenesis

    Directory of Open Access Journals (Sweden)

    Li-Ling Chang

    2012-05-01

    Full Text Available The purpose of the study was to investigate the antioxidant characteristics of Anisomeles indica methanol extract and the inhibitory effect of ovatodiolide on melanogenesis. In the study, the antioxidant capacities of A. indica methanol extract such as DPPH assay, ABTS radical scavenging assay, reducing capacity and metal ion chelating capacity as well as total phenolic content of the extract were investigated. In addition,<strong> strong>the inhibitory effects of ovatodiolide on mushroom tyrosinase, B16F10 intracellular tyrosinase and melanin content were determined spectrophotometrically. Our results revealed that the antioxidant capacities of A. indica methanol extract increased in a dose-dependent pattern. The purified<strong> strong>ovatodiolide inhibited mushroom tyrosinase activity (IC50 = 0.253 mM, the compound also effectively suppressed intracellular tyrosinase activity (IC50 = 0.469 mM and decreased the amount of melanin (IC50 = 0.435 mM in a dose-dependent manner in B16F10 cells. Our results concluded that A. indica methanol extract displays antioxidant capacities and ovatodiolide purified from the extract inhibited melanogenesis in B16F10 cells. Hence, A. indica methanol extract and ovatodiolide could be applied as a type of dermatological whitening agent in skin care products.

  14. Reverse engineering truncations of an antimicrobial peptide dimer to identify the origins of potency and broad spectrum of action.

    Science.gov (United States)

    Anantharaman, Aparna; Sahal, Dinkar

    2010-08-26

    Antimicrobial peptides hold promise against antibiotic resistant pathogens. Here, to find the physicochemical origins of potency and broad spectrum antimicrobial action, we report the structure-activity relationships of synthetic intermediates (peptides A-D) of a potent lysine branched dimeric antibacterial peptide DeltaFd. Our studies show that a tetracationic character in a weak helical fold (peptide C) elicits potent but narrow spectrum antimicrobial activity [Minimum inhibitory concentrations (MICs) E. coli 10 microM, S. aureus>100 microM]. In contrast, a hexacationic character in a strong, amphipathic helix (DeltaFd) confers potent and broad spectrum action [MICs E. coli 2.5 microM, S. aureus 5 microM]. While DeltaFd caused rapid and potent permeabilization of the E. coli membranes, the less helical intermediates (peptides A-D) showed slow and weak to no responses. Two seminal findings that may aid future drug design are (a) at identical helicity, increasing charge enhanced outer membrane permeabilization, and (b) at identical charge, increasing helicity stimulated rate of outer membrane permeabilization and kill kinetics besides enhancing potency leading to broad spectrum action.

  15. New Indole Alkaloids from the Bark of Rauvolfia Reflexa and their Cholinesterase Inhibitory Activity

    Directory of Open Access Journals (Sweden)

    Mehran Fadaeinasab

    2015-11-01

    Full Text Available Background/Aims: Rauvolfia reflexa is a member of the Apocynaceae family. Plants from the Apocynaceae family have been traditionally used in the treatment of age-related brain disorders Methods and Results: Two new indole alkaloids, rauvolfine C (1 and 3-methyl-10,11-dimethoxy-6-methoxycarbonyl-β-carboline (2, along with five known, macusine B (3, vinorine (4, undulifoline (5, isoresrpiline (6 and rescinnamine (7 were isolated from the bark of Rauvolfia reflexa. Cholinesterase inhibitory assay and molecular docking were performed to get insight of the inhibitory activity and molecular interactions of the compounds. The compounds showed good to moderate cholinesterase inhibitory activity with IC50 values in the range of 8.06 to 73.23 µM. Compound 7 was found to be the most potent inhibitor of both acetylcholinesterase (AChE and butyrylcholinesterase (BChE. Compounds 1, 2, 5 and 6 were found to be selective towards BChE, while compounds 3, 4 and 7 were dual inhibitors, having almost equal inhibitory activity on both AChE and BChE. Molecular docking revealed that compounds 6 and 7 interacted differently on AChE and BChE, by means of hydrophobic interactions and hydrogen bonding. In AChE, the indole moiety of both compounds interacted with the residues lining the peripheral anionic site, whereas in BChE, their methoxy groups are primarily responsible for the strong inhibitory activity via interactions with residues at the active site of the enzyme. Conclusion: Two new and five known indole alkaloids were isolated from R. reflexa. Among the compounds, 7 and 6 showed the most potent and promising cholinesterase inhibitory activity, worthy for further investigations.

  16. New Indole Alkaloids from the Bark of Rauvolfia Reflexa and their Cholinesterase Inhibitory Activity.

    Science.gov (United States)

    Fadaeinasab, Mehran; Basiri, Alireza; Kia, Yalda; Karimian, Hamed; Ali, Hapipah Mohd; Murugaiyah, Vikneswaran

    2015-01-01

    Rauvolfia reflexa is a member of the Apocynaceae family. Plants from the Apocynaceae family have been traditionally used in the treatment of age-related brain disorders Methods and Results: Two new indole alkaloids, rauvolfine C (1) and 3-methyl-10,11-dimethoxy-6-methoxycarbonyl-β-carboline (2), along with five known, macusine B (3), vinorine (4), undulifoline (5), isoresrpiline (6) and rescinnamine (7) were isolated from the bark of Rauvolfia reflexa. Cholinesterase inhibitory assay and molecular docking were performed to get insight of the inhibitory activity and molecular interactions of the compounds. The compounds showed good to moderate cholinesterase inhibitory activity with IC50 values in the range of 8.06 to 73.23 µM. Compound 7 was found to be the most potent inhibitor of both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Compounds 1, 2, 5 and 6 were found to be selective towards BChE, while compounds 3, 4 and 7 were dual inhibitors, having almost equal inhibitory activity on both AChE and BChE. Molecular docking revealed that compounds 6 and 7 interacted differently on AChE and BChE, by means of hydrophobic interactions and hydrogen bonding. In AChE, the indole moiety of both compounds interacted with the residues lining the peripheral anionic site, whereas in BChE, their methoxy groups are primarily responsible for the strong inhibitory activity via interactions with residues at the active site of the enzyme. Two new and five known indole alkaloids were isolated from R. reflexa. Among the compounds, 7 and 6 showed the most potent and promising cholinesterase inhibitory activity, worthy for further investigations. © 2015 S. Karger AG, Basel.

  17. New tyrosinase inhibitory decapeptide: Molecular insights into the role of tyrosine residues.

    Science.gov (United States)

    Ochiai, Akihito; Tanaka, Seiya; Imai, Yuta; Yoshida, Hisashi; Kanaoka, Takumi; Tanaka, Takaaki; Taniguchi, Masayuki

    2016-06-01

    Tyrosinase, a rate-limiting enzyme in melanin biosynthesis, catalyzes the hydroxylation of l-tyrosine to 3,4-dihydroxy-l-phenylalanine (l-dopa) (monophenolase reaction) and the subsequent oxidation of l-dopa to l-dopaquinone (diphenolase reaction). Thus, tyrosinase inhibitors have been proposed as skin-lightening agents; however, many of the existing inhibitors cannot be widely used in the cosmetic industry due to their high cytotoxicity and instability. On the other hand, some tyrosinase inhibitory peptides have been reported as safe. In this study, we found that the peptide TH10, which has a similar sequence to the characterized inhibitory peptide P4, strongly inhibits the monophenolase reaction with a half-maximal inhibitory concentration of 102 μM. Seven of the ten amino acid residues in TH10 were identical to P4; however, TH10 possesses one N-terminal tyrosine, whereas P4 contains three tyrosine residues located at its N-terminus, center, and C-terminus. Subsequent analysis using sequence-shuffled variants indicated that the tyrosine residues located at the N-terminus and center of P4 have little to no contribution to its inhibitory activity. Furthermore, docking simulation analysis of these peptides with mushroom tyrosinase demonstrated that the active tyrosine residue was positioned close to copper ions, suggesting that TH10 and P4 bind to tyrosinase as a substrate analogue. Copyright © 2015 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  18. Inhibitory Control and Hedonic Response towards Food Interactively Predict Success in a Weight Loss Programme for Adults with Obesity

    Directory of Open Access Journals (Sweden)

    Timo Brockmeyer

    2016-10-01

    Full Text Available Objective: Low inhibitory control and strong hedonic response towards food are considered to contribute to overeating and obesity. Based on previous research, the present study aimed at examining the potentially crucial interplay between these two factors in terms of long-term weight loss in people with obesity. Methods: BMI, inhibitory control towards food, and food liking were assessed in obese adults prior to a weight reduction programme (OPTIFAST® 52. After the weight reduction phase (week 13 and the weight loss maintenance phase (week 52, participants' BMI was re-assessed. Results: Baseline BMI, inhibitory control and food liking alone did not predict weight loss. As hypothesised, however, inhibitory control and food liking interactively predicted weight loss from baseline to week 13 and to week 52 (albeit the latter effect was less robust. Participants with low inhibitory control and marked food liking were less successful in weight reduction. Conclusion: These findings underscore the relevance of the interplay between cognitive control and food reward valuation in the maintenance of obesity.

  19. VGLUT3 does not synergize GABA/glycine release during functional refinement of an inhibitory auditory circuit

    Directory of Open Access Journals (Sweden)

    Daniel T Case

    2014-11-01

    Full Text Available The vesicular glutamate transporter VGLUT3 is expressed at several locations not normally associated with glutamate release. Although the function of this protein remains generally elusive, when expressed in non-glutamatergic synaptic terminals, VGLUT3 can not only allow glutamate co-transmission but also synergize the action of non-glutamate vesicular transporters. Interestingly, in the immature glycinergic projection between the medial nucleus of the trapezoid body (MNTB and the lateral superior olive (LSO of auditory brainstem, the transient early expression of VGLUT3 is required for normal developmental refinement. It has however been unknown whether the primary function of VGLUT3 in development of these inhibitory synapses is to enable glutamate release or to promote loading of inhibitory neurotransmitter through vesicular synergy. Using tissue from young mice in which Vglut3 had been genetically deleted, we evaluated inhibitory neurotransmission in the MNTB-LSO pathway. Our results show, in contrast to what has been seen at adult synapses, that VGLUT3 expression has little or no effect on vesicular synergy at the immature glycinergic synapse of brainstem. This finding supports the model that the primary function of increased VGLUT3 expression in the immature auditory brainstem is to enable glutamate release in a developing inhibitory circuit.

  20. Phase transition from strong-coupling expansion

    International Nuclear Information System (INIS)

    Polonyi, J.; Szlachanyi, K.

    1982-01-01

    Starting with quarkless SU(2) lattice gauge theory and using the strong-coupling expansion we calculate the action of the effective field theory which corresponds to the thermal Wilson loop. This effective action makes evident that the quark liberating phase transition traces back to the spontaneous breaking of a global Z(2) symmetry group. It furthermore describes both phases qualitatively. (orig.)

  1. Inhibitory effect of unlabeled iodothyronines on the deiodination of labeled thyroid hormones by cultured hepatocarcinoma cells

    International Nuclear Information System (INIS)

    Sorimachi, Kenji

    1980-01-01

    Inhibitory effects of unlabeled iodothyronines on the metabolism of thyroxine (T 4 ), 3,3',5-triiodothyronine (T 3 ) and 3,3',5'-triiodothyronine (reverse T 3 , rT 3 ) were investigated in continuously cultured monkey hepatocarcinoma cells which showed a rapid metabolism of the thyroid hormones. Nonphenolic ring deiodination of [3',5'- 125 I]-T 4 and [3'- 125 I]-T 3 was strongly inhibited by excess T 3 , 3,5-diiodothyronine (3,5-T 2 ) and T 4 , whereas rT 3 was the least effective inhibitor. Phenolic ring deiodination of [3',5'- 125 I]-rT 3 was strongly affected by excess unlabeled rT 3 . However, the inhibitory effect of T 4 , T 3 and 3,5-T 3 was much weaker than that of rT 3 . It was concluded that rT 3 is apparently the most effective inhibitor of phenolic ring deiodination but the least effective inhibitor of nonphenolic ring deiodination. (author)

  2. Active action potential propagation but not initiation in thalamic interneuron dendrites

    Science.gov (United States)

    Casale, Amanda E.; McCormick, David A.

    2012-01-01

    Inhibitory interneurons of the dorsal lateral geniculate nucleus of the thalamus modulate the activity of thalamocortical cells in response to excitatory input through the release of inhibitory neurotransmitter from both axons and dendrites. The exact mechanisms by which release can occur from dendrites are, however, not well understood. Recent experiments using calcium imaging have suggested that Na/K based action potentials can evoke calcium transients in dendrites via local active conductances, making the back-propagating action potential a candidate for dendritic neurotransmitter release. In this study, we employed high temporal and spatial resolution voltage-sensitive dye imaging to assess the characteristics of dendritic voltage deflections in response to Na/K action potentials in interneurons of the mouse dorsal lateral geniculate nucleus. We found that trains or single action potentials elicited by somatic current injection or local synaptic stimulation led to action potentials that rapidly and actively back-propagated throughout the entire dendritic arbor and into the fine filiform dendritic appendages known to release GABAergic vesicles. Action potentials always appeared first in the soma or proximal dendrite in response to somatic current injection or local synaptic stimulation, and the rapid back-propagation into the dendritic arbor depended upon voltage-gated sodium and TEA-sensitive potassium channels. Our results indicate that thalamic interneuron dendrites integrate synaptic inputs that initiate action potentials, most likely in the axon initial segment, that then back-propagate with high-fidelity into the dendrites, resulting in a nearly synchronous release of GABA from both axonal and dendritic compartments. PMID:22171033

  3. Synaptic reorganization of inhibitory hilar interneuron circuitry after traumatic brain injury in mice

    Science.gov (United States)

    Hunt, Robert F.; Scheff, Stephen W.; Smith, Bret N.

    2011-01-01

    Functional plasticity of synaptic networks in the dentate gyrus has been implicated in the development of posttraumatic epilepsy and in cognitive dysfunction after traumatic brain injury, but little is known about potentially pathogenic changes in inhibitory circuits. We examined synaptic inhibition of dentate granule cells and excitability of surviving GABAergic hilar interneurons 8–13 weeks after cortical contusion brain injury in transgenic mice that express enhanced green fluorescent protein in a subpopulation of inhibitory neurons. Whole-cell voltage-clamp recordings in granule cells revealed a reduction in spontaneous and miniature IPSC frequency after head injury; no concurrent change in paired-pulse ratio was found in granule cells after paired electrical stimulation of the hilus. Despite reduced inhibitory input to granule cells, action potential and EPSC frequencies were increased in hilar GABA neurons from slices ipsilateral to the injury, versus those from control or contralateral slices. Further, increased excitatory synaptic activity was detected in hilar GABA neurons ipsilateral to the injury after glutamate photostimulation of either the granule cell or CA3 pyramidal cell layers. Together, these findings suggest that excitatory drive to surviving hilar GABA neurons is enhanced by convergent input from both pyramidal and granule cells, but synaptic inhibition of granule cells is not fully restored after injury. This rewiring of circuitry regulating hilar inhibitory neurons may reflect an important compensatory mechanism, but it may also contribute to network destabilization by increasing the relative impact of surviving individual interneurons in controlling granule cell excitability in the posttraumatic dentate gyrus. PMID:21543618

  4. Analysis of the synaptotagmin family during reconstituted membrane fusion. Uncovering a class of inhibitory isoforms.

    Science.gov (United States)

    Bhalla, Akhil; Chicka, Michael C; Chapman, Edwin R

    2008-08-01

    Ca(2+)-triggered exocytosis in neurons and neuroendocrine cells is regulated by the Ca(2+)-binding protein synaptotagmin (syt) I. Sixteen additional isoforms of syt have been identified, but little is known concerning their biochemical or functional properties. Here, we assessed the abilities of fourteen syt isoforms to directly regulate SNARE (soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein receptor)-catalyzed membrane fusion. One group of isoforms stimulated neuronal SNARE-mediated fusion in response to Ca(2+), while another set inhibited SNARE catalyzed fusion in both the absence and presence of Ca(2+). Biochemical analysis revealed a strong correlation between the ability of syt isoforms to bind 1,2-dioleoyl phosphatidylserine (PS) and t-SNAREs in a Ca(2+)-promoted manner with their abilities to enhance fusion, further establishing PS and SNAREs as critical effectors for syt action. The ability of syt I to efficiently stimulate fusion was specific for certain SNARE pairs, suggesting that syts might contribute to the specificity of intracellular membrane fusion reactions. Finally, a subset of inhibitory syts down-regulated the ability of syt I to activate fusion, demonstrating that syt isoforms can modulate the function of each other.

  5. Impulsivity: A deficiency of inhibitory control?

    NARCIS (Netherlands)

    Lansbergen, M.M.

    2007-01-01

    Impulsivity has been defined as acting without thinking. Impulsivity can be quantified by impulsivity questionnaires, but also by behavioral paradigms which tax inhibitory control. Previous research has repeatedly demonstrated deficient inhibitory control in psychopathological samples characterized

  6. Preliminary pharmacological studies on Eugenia uniflora leaves: xanthine oxidase inhibitory activity.

    Science.gov (United States)

    Schmeda-Hirschmann, G; Theoduloz, C; Franco, L; Ferro, E; de Arias, A R

    1987-11-01

    Eugenia uniflora is widely used in Paraguayan folk medicine. A hydroalcoholic extract of the leaves showed some central nervous system activity in hippocratic screening when given intraperitoneally, but little to no acute or subacute toxicity in doses up to 4200 mg/kg orally in BALB c mice. The LD50 of the extract was 220 mg/kg i.p. in mice. A decoction or infusion of the leaves is recommended for treating gout by native herbalists. The known flavonoids quercitrin, quercetin, myricitrin and myricetin were found to be responsible for the xanthine oxidase inhibitory action of the plant extract.

  7. Combined Activity of Colloid Nanosilver and Zataria Multiflora Boiss Essential Oil-Mechanism of Action and Biofilm Removal Activity

    Directory of Open Access Journals (Sweden)

    Maryam Shirdel

    2017-12-01

    Full Text Available Purpose: The aim of this study was to investigate antimicrobial and biofilm removal potential of Zataria multiflora essential oil (ZEO and silver nanoparticle (SNP alone and in combination on Staphylococcus aureus and Salmonella Typhimurium and evaluate the mechanism of action. Methods: The minimum inhibitory concentration (MIC, and optimal inhibitory combination (OIC of ZEO and SNP were determined according to fractional inhibitory concentration (FIC method. Biofilm removal potential and leakage pattern of 260-nm absorbing material from the bacterial cell during exposure to the compounds were also investigated. Results: MICs of SNP for both bacteria were the same as 25 μg/ mL. The MICs and MBCs values of ZEO were 2500 and 1250 μg/mL, respectively. The most effective OIC value for SNP and ZEO against Salm. Typhimurium and Staph. aureus were 12.5, 625 and 0.78, 1250 μg/ mL, respectively. ZEO and SNP at MIC and OIC concentrations represented a strong removal ability (>70% on biofilm. Moreover, ZEO at MIC and OIC concentrations did a 6-log reduction of primary inoculated bacteria during 15 min contact time. The effect of ZEO on the loss of 260-nm material from the cell was faster than SNP during 15 and 60 min. Conclusion: Combination of ZEO and SNP had significant sanitizing activity on examined bacteria which may be suitable for disinfecting the surfaces.

  8. Amino acid neurotransmitters and new approaches to anticonvulsant drug action.

    Science.gov (United States)

    Meldrum, B

    1984-01-01

    Amino acids provide the most universal and important inhibitory (gamma-aminobutyric acid (GABA), glycine) and excitatory (glutamate, aspartate, cysteic acid, cysteine sulphinic acid) neurotransmitters in the brain. An anticonvulsant action may be produced (1) by enhancing inhibitory (GABAergic) processes, and (2) by diminishing excitatory transmission. Possible pharmacological mechanisms for enhancing GABA-mediated inhibition include (1) GABA agonist action, (2) GABA prodrugs, (3) drugs facilitating GABA release from terminals, (4) inhibition of GABA-transaminase, (5) allosteric enhancement of the efficacy of GABA at the receptor complex, (6) direction action on the chloride ionophore, and (7) inhibition of GABA reuptake. Examples of these approaches include the use of irreversible GABA-transaminase inhibitors, such as gamma-vinyl GABA, and the development of anticonvulsant beta-carbolines that interact with the "benzodiazepine receptor." Pharmacological mechanisms for diminishing excitatory transmission include (1) enzyme inhibitors that decrease the maximal rate of synthesis of glutamate or aspartate, (2) drugs that decrease the synaptic release of glutamate or aspartate, and (3) drugs that block the post-synaptic action of excitatory amino acids. Compounds that selectively antagonise excitation due to dicarboxylic amino acids have recently been developed. Those that selectively block excitation produced by N-methyl-D-aspartate (and aspartate) have proved to be potent anticonvulsants in many animal models of epilepsy. This provides a novel approach to the design of anticonvulsant drugs.

  9. Formation of non-equilibrium structures in R6M5 steel under strong pulse beams action

    International Nuclear Information System (INIS)

    Rusin, Yu.G.; Plotnikov, S.V.

    2001-01-01

    Formation of non-equilibrium structures in R6M5 steel surface layer in the supply state under irradiation by strong pulse beams (SPB) is examined. Cylindric samples with diameter 10 mm and height 15 mm of R6M5 fast-cutting steel with following content (weight %): 0.85% C, 0.4% Mn, 0.5% Si, 4.0 Cr; 2.1% V; 5.3% Mo, 6.0% W; 0.4% Ni, Fe (the rest) were examined. Irradiation by SPB was conducted on the 'TEMP' modified accelerator operating in a technological regime with carbon beams parameters: energy from 0.3 up o 0.4 MeV, beam density in an impulse from 20 to 250 A/cm 2 , pulse duration from 60 tp 100 ns. The beam consists of 70 % carbon ions and 30 % hydrogen ions. Phase identification and its structural phase analysis have been studied on the DRON-3 X-ray diffractometer of common assignment. Topography of metallographic specimen surface has been examined on the REM-200 scanning electron microscope. Doping elements redistribution and phases quantitative characteristics after SPB action were studied with help of the X-ray spectral microanalysis (XRSA) on the MS-46 Camebax microanalyzer. Character of doping elements redistribution in the alloy (XRSA data) show its appreciably redistribution, moreover in the melted zone the increased content of molybdenum, tungsten, vanadium is observing, and in the zone of thermal action its increase relatively to matrix values

  10. Length and coverage of inhibitory decision rules

    KAUST Repository

    Alsolami, Fawaz

    2012-01-01

    Authors present algorithms for optimization of inhibitory rules relative to the length and coverage. Inhibitory rules have a relation "attribute ≠ value" on the right-hand side. The considered algorithms are based on extensions of dynamic programming. Paper contains also comparison of length and coverage of inhibitory rules constructed by a greedy algorithm and by the dynamic programming algorithm. © 2012 Springer-Verlag.

  11. Identification of the free phenolic profile of Adlay bran by UPLC-QTOF-MS/MS and inhibitory mechanisms of phenolic acids against xanthine oxidase.

    Science.gov (United States)

    Lin, Lianzhu; Yang, Qingyun; Zhao, Kun; Zhao, Mouming

    2018-07-01

    Adlay bran free phenolic extract has been previously demonstrated to possess potent xanthine oxidase (XOD) inhibitory activity. The aims of this study were to characterize the free phenolic profile of adlay bran and investigate the structure-activity relationship, underlying mechanism and interaction of phenolic acids as XOD inhibitors. A total of twenty phenolics including ten phenolic acids, two coumarins, two phenolic aldedhyes and six flavonoids were identified in a phenolic compound-guided separation by UPLC-QTOF-MS/MS. Adlay bran free phenolic extract possessed strong XOD inhibitory activity related to hydroxycinnamic acids with methoxyl groups. The hydrogen bonding and hydrophobic interactions were the main forces in the binding of adlay phenolics to XOD. Sinapic acid, identified in adlay bran for the first time, possessed strong XOD inhibitory activity in a mixed non-competitive manner, and synergistic effects with other adlay phenolic acids at low concentrations, and would be a promising agent for preventing and treating hyperuricemia. Copyright © 2018. Published by Elsevier Ltd.

  12. Inhibitory effect of vanillin on cellulase activity in hydrolysis of cellulosic biomass.

    Science.gov (United States)

    Li, Yun; Qi, Benkun; Wan, Yinhua

    2014-09-01

    Pretreatment of lignocellulosic material produces a wide variety of inhibitory compounds, which strongly inhibit the following enzymatic hydrolysis of cellulosic biomass. Vanillin is a kind of phenolics derived from degradation of lignin. The effect of vanillin on cellulase activity for the hydrolysis of cellulose was investigated in detail. The results clearly showed that vanillin can reversibly and non-competitively inhibit the cellulase activity at appropriate concentrations and the value of IC50 was estimated to be 30 g/L. The inhibition kinetics of cellulase by vanillin was studied using HCH-1 model and inhibition constants were determined. Moreover, investigation of three compounds with similar structure of vanillin on cellulase activity demonstrated that aldehyde group and phenolic hydroxyl groups of vanillin had inhibitory effect on cellulase. These results provide valuable and detailed information for understanding the inhibition of lignin derived phenolics on cellulase. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. Inhibitory effect of piperine on Helicobacter pylori growth and adhesion to gastric adenocarcinoma cells

    OpenAIRE

    Tharmalingam, Nagendran; Kim, Sa-Hyun; Park, Min; Woo, Hyun Jun; Kim, Hyun Woo; Yang, Ji Yeong; Rhee, Ki-Jong; Kim, Jong Bae

    2014-01-01

    Background Piperine is a compound comprising 5-9% of black pepper (Piper nigrum), which has a variety of biological roles related to anticancer activities. Helicobacter pylori has been classified as a gastric carcinogen, because it causes gastritis and gastric cancer by injecting the virulent toxin CagA and translocating VacA. The present study investigated the inhibitory action of piperine on H. pylori growth and adhesion. Methods Inhibition of H. pylori growth was determined by the broth ma...

  14. Inhibitory and bactericidal action of the biocorrosion agents «INCORGAS» and «AMDOR».

    Science.gov (United States)

    Tsygankova, L E; Vigdorovich, V I; Esina, M N; Nazina, T N; Dubinskaya, E V

    2014-06-01

    Inhibiting action of A, B and M-X compositions against hydrosulfide corrosion of carbon steel, hydrogen diffusion through the steel membrane has been studied along with their bactericidal effect with respect to sulfate-reducing bacteria of Desulfomicrobium type. Bactericidal properties of the compositions have been studied in the Postgate medium. Corrosion tests have been made in the NACE medium saturated by hydrogen sulfide and carbon dioxide separately and together by methods of gravimetrical measurements and linear polarization resistance (LRP). Potentiodynamic polarization and electrochemical diffusion method have been used. Steel protection is determined in the inhibited solutions by combined action of corrosion products film and inhibitor. Presence of sulfate-reducing bacteria in medium increases hydrogen diffusion flux through the steel membrane by 2-3 times and essentially stimulates effect of the inhibitors. The inhibiting compositions decrease quantity of sulfate-reducing bacteria (SRB) by 95-98%. The obtained results testify about predominately bacteriostatic action of the inhibiting compositions, which has influence on the enzymatic systems of SRB cells responsible directly for the sulfate reduction because of substantially decreasing the biogenic hydrogen sulfide concentration in the system. © 2013 Elsevier B.V. All rights reserved.

  15. The frontal lobes and inhibitory function

    International Nuclear Information System (INIS)

    Konishi, Seiki

    2011-01-01

    Neuropsychological studies using traditional tasks of inhibitory functions, such as the Wisconsin card sorting test (WCST) and the Go/No-Go Task have revealed that the frontal lobe is responsible for several types of inhibitory functions. However, the detailed psychological nature of the inhibitory functions and the precise location of their critical foci within the frontal lobe remain to be investigated. Functional magnetic resonance imaging provides spatial and temporal resolution that allowed us to illuminate at least 4 frontal regions involved in inhibitory functions: the dorsolateral, ventrolateral, and rostral parts of the frontal lobe and the presupplementary motor area (preSMA). The ventrolateral part of the frontal lobe in the right hemisphere was activated during response inhibition. The preSMA in the left hemisphere was activated during inhibition of proactive interference immediately after the dimension changes of the WCST. The rostral part of the frontal lobe in the left hemisphere was activated during inhibition long after the dimension changes. The dorsolateral part of the frontal lobe in the left hemisphere was activated at the dimension changes in the first time, but not in the second time. These findings provide clues to our understanding of functional differentiation of inhibitory functions and their localization in the frontal lobe. (author)

  16. Muscarinic receptors modulate dendrodendritic inhibitory synapses to sculpt glomerular output.

    Science.gov (United States)

    Liu, Shaolin; Shao, Zuoyi; Puche, Adam; Wachowiak, Matt; Rothermel, Markus; Shipley, Michael T

    2015-04-08

    Cholinergic [acetylcholine (ACh)] axons from the basal forebrain innervate olfactory bulb glomeruli, the initial site of synaptic integration in the olfactory system. Both nicotinic acetylcholine receptors (nAChRs) and muscarinic acetylcholine receptors (mAChRs) are expressed in glomeruli. The activation of nAChRs directly excites both mitral/tufted cells (MTCs) and external tufted cells (ETCs), the two major excitatory neurons that transmit glomerular output. The functional roles of mAChRs in glomerular circuits are unknown. We show that the restricted glomerular application of ACh causes rapid, brief nAChR-mediated excitation of both MTCs and ETCs in the mouse olfactory bulb. This excitation is followed by mAChR-mediated inhibition, which is blocked by GABAA receptor antagonists, indicating the engagement of periglomerular cells (PGCs) and/or short axon cells (SACs), the two major glomerular inhibitory neurons. Indeed, selective activation of glomerular mAChRs, with ionotropic GluRs and nAChRs blocked, increased IPSCs in MTCs and ETCs, indicating that mAChRs recruit glomerular inhibitory circuits. Selective activation of glomerular mAChRs in the presence of tetrodotoxin increased IPSCs in all glomerular neurons, indicating action potential-independent enhancement of GABA release from PGC and/or SAC dendrodendritic synapses. mAChR-mediated enhancement of GABA release also presynaptically suppressed the first synapse of the olfactory system via GABAB receptors on sensory terminals. Together, these results indicate that cholinergic modulation of glomerular circuits is biphasic, involving an initial excitation of MTC/ETCs mediated by nAChRs followed by inhibition mediated directly by mAChRs on PGCs/SACs. This may phasically enhance the sensitivity of glomerular outputs to odorants, an action that is consistent with recent in vivo findings. Copyright © 2015 the authors 0270-6474/15/355680-13$15.00/0.

  17. Recruitment of local inhibitory networks by horizontal connections in layer 2/3 of ferret visual cortex.

    Science.gov (United States)

    Tucker, Thomas R; Katz, Lawrence C

    2003-01-01

    To investigate how neurons in cortical layer 2/3 integrate horizontal inputs arising from widely distributed sites, we combined intracellular recording and voltage-sensitive dye imaging to visualize the spatiotemporal dynamics of neuronal activity evoked by electrical stimulation of multiple sites in visual cortex. Individual stimuli evoked characteristic patterns of optical activity, while delivering stimuli at multiple sites generated interacting patterns in the regions of overlap. We observed that neurons in overlapping regions received convergent horizontal activation that generated nonlinear responses due to the emergence of large inhibitory potentials. The results indicate that co-activation of multiple sets of horizontal connections recruit strong inhibition from local inhibitory networks, causing marked deviations from simple linear integration.

  18. Evaluation of phenolic profile, enzyme inhibitory and antimicrobial activities of Nigella sativa L. seed extracts

    Directory of Open Access Journals (Sweden)

    Anela Topcagic

    2017-11-01

    Full Text Available Black cumin (Nigella sativa L. [N.sativa] seed extracts demonstrated numerous beneficial biological effects including, among others, antidiabetic, anticancer, immunomodulatory, antimicrobial, anti-inflammatory, antihypertensive, and antioxidant activity. To better understand the phytochemical composition of N. sativa seeds, methanol seed extracts were analyzed for phenolic acid and flavonoid content. Furthermore, we tested N. sativa methanol, n-hexane, and aqueous seed extracts for their inhibitory activity against butyrylcholinesterase (BChE and catalase (CAT as well as for antimicrobial activity against several bacterial and a yeast strains. The phenolic content of N. sativa was analyzed using ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS. The inhibition of BChE was assessed by modified Ellman’s method, and the inhibition of CAT was determined by monitoring hydrogen peroxide consumption. The extracts were tested against Bacillus subtilis, Staphylococcus aureus, Salmonella enterica, and Escherichia coli using the agar diffusion method. The UHPLC-MS/MS method allowed the identification and quantification of 23 phenolic compounds within 15 minutes. The major components found in N. sativa seed extract were sinapinic acid (7.22 ± 0.73 µg/mg as a phenolic acid and kaempferol (11.74 ± 0.92 µg/mg as a flavonoid. All extracts showed inhibitory activity against BChE, with methanol seed extract demonstrating the highest inhibitory activity (inhibitory concentration 50% [IC50] 79.11 ± 6.06 µg/ml. The methanol seed extract also showed strong inhibitory activity against CAT with an IC50 value of 6.61 ± 0.27 µg/ml. Finally, the methanol extract exhibited considerable inhibitory activity against the tested microbial strains. Overall, this is the first study to investigate the ability of black cumin seed extracts to inhibit CAT. Our results indicate that N. sativa seed can be considered as an effective inhibitor

  19. Zeolites relieves inhibitory stress from high concentrations of long chain fatty acids.

    Science.gov (United States)

    Nordell, Erik; Hansson, Anna B; Karlsson, Martin

    2013-12-01

    Protein and fat rich slaughterhouse waste is a very attractive waste stream for the production of biogas because of the high biochemical methane potential of the substrate. The material has however some drawbacks as the sole material for biogas production due to the production of several process disturbing metabolites such as ammonia, sulfides and long chain fatty acids. We can in this work present results that show that zeolites have the potential to relieve inhibitory stress from the presence of long chain fatty acids. Moreover, the results strongly indicate that it is mainly acetic acid consumers that are most negatively affected by long chain fatty acids and that the mechanism of stress relief is an adsorption of long chain fatty acids to the zeolites. In addition to this, it is shown that the effect is immediate and that only a small amount of zeolites is necessary to cancel the inhibitory effect of long chain fatty acids. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. Inhibitory effect of unlabeled iodothyronines on the deiodination of labeled thyroid hormones by cultured hepatocarcinoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Sorimachi, K [Dokkyo Univ. Tochigi (Japan). School of Medicine

    1980-04-01

    Inhibitory effects of unlabeled iodothyronines on the metabolism of thyroxine (T/sub 4/), 3,3',5-triiodothyronine (T/sub 3/) and 3,3',5'-triiodothyronine (reverse T/sub 3/, rT/sub 3/) were investigated in continuously cultured monkey hepatocarcinoma cells which showed a rapid metabolism of the thyroid hormones. Nonphenolic ring deiodination of (3',5'-/sup 125/I)-T/sub 4/ and (3'-/sup 125/I)-T/sub 3/ was strongly inhibited by excess T/sub 3/, 3,5-diiodothyronine (3,5-T/sub 2/) and T/sub 4/, whereas rT/sub 3/ was the least effective inhibitor. Phenolic ring deiodination of (3',5'-/sup 125/I)-rT/sub 3/ was strongly affected by excess unlabeled rT/sub 3/. However, the inhibitory effect of T/sub 4/, T/sub 3/ and 3,5-T/sub 3/ was much weaker than that of rT/sub 3/. It was concluded that rT/sub 3/ is apparently the most effective inhibitor of phenolic ring deiodination but the least effective inhibitor of nonphenolic ring deiodination.

  1. Chemical Composition and Enzymes Inhibitory, Brine Shrimp Larvae Toxicity, Antimicrobial and Antioxidant Activities of Caloplaca biatorina

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    Tahereh Valadbeigi

    2016-10-01

    Full Text Available Background This study evaluated the brine shrimp larvae toxicity and enzymes inhibitory especially anti-diabetic potential of Caloplaca biatorina via in vitro inhibition of α-amylase and α-glucosidase using the methanol extracts. Also aldehyde oxidase and xanthine oxidase enzymes inhibitory, cytotoxicity, and antioxidant activities of the species were determined. Methods In this experimental study, different concentrations of the extracts (0.2, 5.0, 1 and 1.5 mg/mL were incubated with enzyme substrate solution and the percentage of enzyme inhibitory activity and IC50 was calculated. Folin- Ciocalteu reagent and aluminium chloride colorimetric methods were used to estimate total phenolic and flavonoid content of extracts. The toxicity of the extract was assessed using the brine shrimp lethality bioassay. The minimal inhibitory concentration (MIC and minimum bactericidal concentration (MBC were determined. High-performance liquid chromatography and Thin-layer chromatography analysis were evaluated. The data were analyzed by SPSS V.21 software. Results Parietin, Emodin, 1,8-Dihydroxy-3-(hydroxymethyl-6- methoxy-9.10-anthracenedione and Rhein were identified. The extract showed strong α-glucosidase, aldehyde oxidase and xanthine oxidase inhibitory activities with IC50 value of 17.12, 40.09 and 11.02 µg/mL respectively. Also methanol extract displayed the strongest DPPH radical scavenging and brine shrimp toxicity (IC50 = 91.11 properties. Conclusions The result obtained suggests that the C. biatorina extract can be classified as non-toxic. Also, it revealed the antioxidant and antidiabetic potential of the lichen.

  2. Inhibitory Activity of Yokukansankachimpihange against Nerve Growth Factor-Induced Neurite Growth in Cultured Rat Dorsal Root Ganglion Neurons

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    Chiaki Murayama

    2015-08-01

    Full Text Available Chronic pruritus is a major and distressing symptom of many cutaneous diseases, however, the treatment remains a challenge in the clinic. The traditional Chinese-Japanese medicine (Kampo medicine is a conservative and increasingly popular approach to treat chronic pruritus for both patients and medical providers. Yokukansankachimpihange (YKH, a Kampo formula has been demonstrated to be effective in the treatment of itching of atopic dermatitis in Japan although its pharmacological mechanism is unknown clearly. In an attempt to clarify its pharmacological actions, in this study, we focused on the inhibitory activity of YKH against neurite growth induced with nerve growth factor (NGF in cultured rat dorsal root ganglion (DRG neurons because epidermal hyperinnervation is deeply related to itch sensitization. YKH showed approximately 200-fold inhibitory activity against NGF-induced neurite growth than that of neurotropin (positive control, a drug used clinically for treatment of chronic pruritus. Moreover, it also found that Uncaria hook, Bupleurum root and their chemical constituents rhynchophylline, hirsutine, and saikosaponin a, d showed inhibitory activities against NGF-induced neurite growth, suggesting they should mainly contribute to the inhibitory activity of YKH. Further study on the effects of YKH against epidermal nerve density in “itch-scratch” animal models is under investigation.

  3. A Subtype of Inhibitory Interneuron with Intrinsic Persistent Activity in Human and Monkey Neocortex

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    Bo Wang

    2015-03-01

    Full Text Available A critical step in understanding the neural basis of human cognitive functions is to identify neuronal types in the neocortex. In this study, we performed whole-cell recording from human cortical slices and found a distinct subpopulation of neurons with intrinsic persistent activity that could be triggered by single action potentials (APs but terminated by bursts of APs. This persistent activity was associated with a depolarizing plateau potential induced by the activation of a persistent Na+ current. Single-cell RT-PCR revealed that these neurons were inhibitory interneurons. This type of neuron was found in different cortical regions, including temporal, frontal, occipital, and parietal cortices in human and also in frontal and temporal lobes of nonhuman primate but not in rat cortical tissues, suggesting that it could be unique to primates. The characteristic persistent activity in these inhibitory interneurons may contribute to the regulation of pyramidal cell activity and participate in cortical processing.

  4. Angiotensin-I Converting Enzyme (ACE Inhibitory and Anti-Oxidant Activities of Sea Cucumber (Actinopyga lecanora Hydrolysates

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    Raheleh Ghanbari

    2015-12-01

    Full Text Available In recent years, food protein-derived hydrolysates have received considerable attention because of their numerous health benefits. Amongst the hydrolysates, those with anti-hypertensive and anti-oxidative activities are receiving special attention as both activities can play significant roles in preventing cardiovascular diseases. The present study investigated the angiotensin-I converting enzyme (ACE inhibitory and anti-oxidative activities of Actinopyga lecanora (A. lecanora hydrolysates, which had been prepared by alcalase, papain, bromelain, flavourzyme, pepsin, and trypsin under their optimum conditions. The alcalase hydrolysate showed the highest ACE inhibitory activity (69.8% after 8 h of hydrolysis while the highest anti-oxidative activities measured by 2,2-diphenyl 1-1-picrylhydrazyl radical scavenging (DPPH (56.00% and ferrous ion-chelating (FIC (59.00% methods were exhibited after 24 h and 8 h of hydrolysis, respectively. The ACE-inhibitory and anti-oxidative activities displayed dose-dependent trends, and increased with increasing protein hydrolysate concentrations. Moreover, strong positive correlations between angiotensin-I converting enzyme (ACE inhibitory and anti-oxidative activities were also observed. This study indicates that A. lecanora hydrolysate can be exploited as a source of functional food owing to its anti-oxidant as well as anti-hypertension functions.

  5. Some characteristics of a raw starch digestion inhibitory factor from Aspergillus niger

    Energy Technology Data Exchange (ETDEWEB)

    Towprayoon, S.; Saha, B.C.; Fujio, Yusaku; Ueda, Seinosuke

    1988-09-01

    The effect of an inhibitory factor (IF) from Aspergillus niger 19 on raw starch digestion by pure glucoamylase I of black Aspergillus, pure glucoamylase of Rhizopus niveus, bacterial ..cap alpha..-amylase, fungal ..cap alpha..-amylase and various combination was investigated. The IF caused higher inhibition of raw starch hydrolysis by the combined action of glucoamylase and fungal ..cap alpha..-amylase than of hydrolysis by the individual enzymes. A protein moiety of IF might play an active part in this inhibition phenomenon. The IF was found to starch granules, preventing hydrolysis by the enzymes, and caused decreased raw starch hydrolysis yields.

  6. Center vortices at strong couplings and all couplings

    International Nuclear Information System (INIS)

    Greensite, J.

    2001-01-01

    Motivations for the center vortex theory of confinement are discussed. In particular, it is noted that the abelian dual Meissner effect, which is the signature of dual superconductivity, cannot adequately describe the confining force at large distance scales. A long-range effective action is derived from strong-coupling lattice gauge theory in D=3 dimensions, and it is shown that center vortices emerge as the stable saddlepoints of this action. Thus, in the case of strong couplings, the vortex picture is arrived at analytically. I also respond briefly to a recent criticism regarding maximal center gauge. (author)

  7. Chemical Constituents of Muehlenbeckia tamnifolia (Kunth) Meisn (Polygonaceae) and Its In Vitro α-Amilase and α-Glucosidase Inhibitory Activities.

    Science.gov (United States)

    Torres-Naranjo, María; Suárez, Alirica; Gilardoni, Gianluca; Cartuche, Luis; Flores, Paola; Morocho, Vladimir

    2016-11-02

    The phytochemical investigation of Muehlenbeckia tamnifolia , collected in Loja-Ecuador, led to the isolation of nine known compounds identified as: lupeol acetate ( 1 ); cis - p -coumaric acid ( 2 ); lupeol ( 3 ); β-sitosterol ( 4 ) trans - p -coumaric acid ( 5 ); linoleic acid ( 6 ) (+)-catechin ( 7 ); afzelin ( 8 ) and quercitrin ( 9 ). The structures of the isolated compounds were determined based on analysis of NMR and MS data, as well as comparison with the literature. The hypoglycemic activity of crude extracts and isolated compounds was assessed by the ability to inhibit α-amylase and α-glucosidase enzymes. The hexane extract showed weak inhibitory activity on α-amylase, with an IC 50 value of 625 µg·mL -1 , while the other extracts and isolated compounds were inactive at the maximum dose tested. The results on α-glucosidase showed more favorable effects; the hexanic and methanolic extracts exhibited a strong inhibitory activity with IC 50 values of 48.22 µg·mL -1 and 19.22 µg·mL -1 , respectively. Four of the nine isolated compounds exhibited strong inhibitory activity with IC 50 values below 8 µM, much higher than acarbose (377 uM). Linoleic acid was the most potent compound (IC 50 = 0.42 µM) followed by afzelin, (+)-catechin and quercitrin.

  8. Inhibitory effects of antimicrobial agents against Fusarium species.

    Science.gov (United States)

    Kawakami, Hideaki; Inuzuka, Hiroko; Hori, Nobuhide; Takahashi, Nobumichi; Ishida, Kyoko; Mochizuki, Kiyofumi; Ohkusu, Kiyofumi; Muraosa, Yasunori; Watanabe, Akira; Kamei, Katsuhiko

    2015-08-01

    We investigated the inhibitory effects of antibacterial, biocidal, and antifungal agents against Fusarium spp. Seven Fusarium spp: four F. falciforme (Fusarium solani species complex), one Fusarium spp, one Fusarium spp. (Fusarium incarnatum-equiseti species complex), and one F. napiforme (Gibberella fujikuroi species complex), isolated from eyes with fungal keratitis were used in this study. Their susceptibility to antibacterial agents: flomoxef, imipenem, gatifloxacin, levofloxacin, moxifloxacin, gentamicin, tobramycin, and Tobracin® (contained 3,000 μg/ml of tobramycin and 25 μg/ml of benzalkonium chloride (BAK), a biocidal agent: BAK, and antifungal agents: amphotericin B, pimaricin (natamycin), fluconazole, itraconazole, miconazole, voriconazole, and micafungin, was determined by broth microdilution tests. The half-maximal inhibitory concentration (IC50), 100% inhibitory concentration (IC100), and minimum inhibitory concentration (MIC) against the Fusarium isolates were determined. BAK had the highest activity against the Fusarium spp. except for the antifungal agents. Three fluoroquinolones and two aminoglycosides had inhibitory effects against the Fusarium spp. at relatively high concentrations. Tobracin® had a higher inhibitory effect against Fusarium spp. than tobramycin alone. Amphotericin B had the highest inhibitory effect against the Fusarium spp, although it had different degrees of activity against each isolate. Our findings showed that fluoroquinolones, aminoglycosides, and BAK had some degree of inhibitory effect against the seven Fusarium isolates, although these agents had considerably lower effect than amphotericin B. However, the inhibitory effects of amphotericin B against the Fusarium spp. varied for the different isolates. Further studies for more effective medications against Fusarium, such as different combinations of antibacterial, biocidal, and antifungal agents are needed. © The Author 2015. Published by Oxford University Press on

  9. Macrophage migration inhibitory factor as an incriminating agent in vitiligo.

    Science.gov (United States)

    Farag, Azza Gaber Antar; Hammam, Mostafa Ahmed; Habib, Mona SalahEldeen; Elnaidany, Nada Farag; Kamh, Mona Eaid

    2018-03-01

    Vitiligo is an autoimmune skin disorder in which the loss of melanocytes is mainly attributed to defective autoimmune mechanisms and, lately, there has been more emphasis on autoinflammatory mediators. Among these is the macrophage migration inhibitory factor, which is involved in many autoimmune skin diseases. However, little is known about the contribution of this factor to vitiligo vulgaris. To determine the hypothesized role of migration inhibitory factor in vitiligo via estimation of serum migration inhibitory factor levels and migration inhibitory factor mRNA concentrations in patients with vitiligo compared with healthy controls. We also aimed to assess whether there is a relationship between the values of serum migration inhibitory factor and/or migration inhibitory factor mRNA with disease duration, clinical type and severity in vitiligo patients. Evaluation of migration inhibitory factor serum level and migration inhibitory factor mRNA expression by ELISA and real-time PCR, respectively, were performed for 50 patients with different degrees of vitiligo severity and compared to 15 age- and gender-matched healthy volunteers as controls. There was a highly significant increase in serum migration inhibitory factor and migration inhibitory factor mRNA levels in vitiligo cases when compared to controls (pvitiligo patients, and each of them with duration and severity of vitiligo. In addition, patients with generalized vitiligo have significantly elevated serum migration inhibitory factor and mRNA levels than control subjects. Small number of investigated subjects. Migration inhibitory factor may have an active role in the development of vitiligo, and it may also be a useful index of disease severity. Consequently, migration inhibitory factor may be a new treatment target for vitiligo patients.

  10. Plant Community Richness Mediates Inhibitory Interactions and Resource Competition between Streptomyces and Fusarium Populations in the Rhizosphere.

    Science.gov (United States)

    Essarioui, Adil; LeBlanc, Nicholas; Kistler, Harold C; Kinkel, Linda L

    2017-07-01

    Plant community characteristics impact rhizosphere Streptomyces nutrient competition and antagonistic capacities. However, the effects of Streptomyces on, and their responses to, coexisting microorganisms as a function of plant host or plant species richness have received little attention. In this work, we characterized antagonistic activities and nutrient use among Streptomyces and Fusarium from the rhizosphere of Andropogon gerardii (Ag) and Lespedeza capitata (Lc) plants growing in communities of 1 (monoculture) or 16 (polyculture) plant species. Streptomyces from monoculture were more antagonistic against Fusarium than those from polyculture. In contrast, Fusarium isolates from polyculture had greater inhibitory capacities against Streptomyces than isolates from monoculture. Although Fusarium isolates had on average greater niche widths, the collection of Streptomyces isolates in total used a greater diversity of nutrients for growth. Plant richness, but not plant host, influenced the potential for resource competition between the two taxa. Fusarium isolates had greater niche overlap with Streptomyces in monoculture than polyculture, suggesting greater potential for Fusarium to competitively challenge Streptomyces in monoculture plant communities. In contrast, Streptomyces had greater niche overlap with Fusarium in polyculture than monoculture, suggesting that Fusarium experiences greater resource competition with Streptomyces in polyculture than monoculture. These patterns of competitive and inhibitory phenotypes among Streptomyces and Fusarium populations are consistent with selection for Fusarium-antagonistic Streptomyces populations in the presence of strong Fusarium resource competition in plant monocultures. Similarly, these results suggest selection for Streptomyces-inhibitory Fusarium populations in the presence of strong Streptomyces resource competition in more diverse plant communities. Thus, landscape-scale variation in plant species richness may be

  11. Self-restraint spillover: Inhibitory control disrupts appetite regulation among ruminators.

    Science.gov (United States)

    Schlinkert, Caroline; Koole, Sander L

    2017-10-23

    People can use inhibitory control to temporarily inhibit their personal preferences to achieve their long-term goals. According to the ego fixation model (Koole et al., 2014), ruminators have difficulties relaxing inhibitory control, leading them to continue inhibiting their personal needs, even when this is no longer required by the situation. Inhibitory control may thus disrupt healthy appetite regulation among ruminators. Among 324 Dutch undergraduate students (218 women; M age  = 21.5), different inhibitory control states were manipulated by varying whether or not participants exerted inhibitory control (Study 1) or priming high versus low inhibitory control (Study 2). All participants then performed a food-tasting task. Healthy appetite regulation was defined as a positive correlation between level of food deprivation and preference for high-calorie foods. For taste ratings, the interaction between inhibitory control and rumination was significant in each study: Inhibitory control disrupted healthy appetite regulation in taste preferences among ruminators, but not among non-ruminators. For eating behavior, the same interaction effect was significant when the two studies were combined. Inhibitory control disrupts healthy appetite regulation among ruminators. These findings suggest the need for caution in interventions that rely on inhibitory control, especially among samples with compulsive thought tendencies. © 2017 Wiley Periodicals, Inc.

  12. Enhancing action of LSD on neuronal responsiveness to serotonin in a brain structure involved in obsessive-compulsive disorder.

    Science.gov (United States)

    Zghoul, Tarek; Blier, Pierre

    2003-03-01

    Potent serotonin (5-HT) reuptake inhibitors are the only drugs that consistently exert a therapeutic action in obsessive-compulsive disorder (OCD). Given that some hallucinogens were reported to exert an anti-OCD effect outlasting their psychotomimetic action, possible modifications of neuronal responsiveness to 5-HT by LSD were examined in two rat brain structures: one associated with OCD, the orbitofrontal cortex (OFC), and another linked to depression, the hippocampus. The effects of concurrent microiontophoretic application of LSD and 5-HT were examined on neuronal firing rate in the rat OFC and hippocampus under chloral hydrate anaesthesia. In order to determine whether LSD could also exert a modification of 5-HT neuronal responsiveness upon systemic administration, after a delay when hallucinosis is presumably no longer present, it was given once daily (100 microg/kg i.p.) for 4 d and the experiments were carried out 24 h after the last dose. LSD attenuated the firing activity of OFC neurons, and enhanced the inhibitory effect of 5-HT when concomitantly ejected on the same neurons. In the hippocampus, LSD also decreased firing rate by itself but decreased the inhibitory action of 5-HT. The inhibitory action of 5-HT was significantly greater in the OFC, but smaller in the hippocampus, when examined after subacute systemic administration of LSD. It is postulated that some hallucinogens could have a beneficial action in OCD by enhancing the responsiveness to 5-HT in the OFC, and not necessarily in direct relation to hallucinosis. The latter observation may have theoretical implications for the pharmacotherapy of OCD.

  13. Inseparability of Go and Stop in Inhibitory Control: Go Stimulus Discriminability Affects Stopping Behavior.

    Science.gov (United States)

    Ma, Ning; Yu, Angela J

    2016-01-01

    Inhibitory control, the ability to stop or modify preplanned actions under changing task conditions, is an important component of cognitive functions. Two lines of models of inhibitory control have previously been proposed for human response in the classical stop-signal task, in which subjects must inhibit a default go response upon presentation of an infrequent stop signal: (1) the race model, which posits two independent go and stop processes that race to determine the behavioral outcome, go or stop; and (2) an optimal decision-making model, which posits that observers decides whether and when to go based on continually (Bayesian) updated information about both the go and stop stimuli. In this work, we probe the relationship between go and stop processing by explicitly manipulating the discrimination difficulty of the go stimulus. While the race model assumes the go and stop processes are independent, and therefore go stimulus discriminability should not affect the stop stimulus processing, we simulate the optimal model to show that it predicts harder go discrimination should result in longer go reaction time (RT), lower stop error rate, as well as faster stop-signal RT. We then present novel behavioral data that validate these model predictions. The results thus favor a fundamentally inseparable account of go and stop processing, in a manner consistent with the optimal model, and contradicting the independence assumption of the race model. More broadly, our findings contribute to the growing evidence that the computations underlying inhibitory control are systematically modulated by cognitive influences in a Bayes-optimal manner, thus opening new avenues for interpreting neural responses underlying inhibitory control.

  14. Inseparability of Go and Stop in Inhibitory Control: Go Stimulus Discriminability Affects Stopping Behavior

    Directory of Open Access Journals (Sweden)

    Ning eMa

    2016-03-01

    Full Text Available Inhibitory control, the ability to stop or modify preplanned actions under changing task conditions, is an important component of cognitive functions. Two lines of models of inhibitory control have previously been proposed for human response in the classical stop-signal task, in which subjects must inhibit a default go response upon presentation of an infrequent stop signal: (1 the race model, which posits two independent go and stop processes that race to determine the behavioral outcome, go or stop; and (2 an optimal decision-making model, which posits that observers decides whether and when to go based on continually (Bayesian updated information about both the go and stop stimuli. In this work, we probe the relationship between go and stop processing by explicitly manipulating the discrimination difficulty of the go stimulus. While the race model assumes the go and stop processes are independent, and therefore go stimulus discriminability should not affect the stop stimulus processing, we simulate the optimal model to show that it predicts harder go discrimination results in a longer go reaction time (RT, a lower stop error rate, as well as a faster stop-signal RT. We then present novel behavioral data that validate these model predictions. The results thus favor a fundamentally inseparable account of go and stop processing, in a manner consistent with the optimal model, and contradicting the independence assumption of the race model. More broadly, our findings contribute to the growing evidence that the computations underlying inhibitory control are systematically modulated by cognitive influences in a Bayes-optimal manner, thus opening new avenues for interpreting neural responses underlying inhibitory control.

  15. Flexible brain network reconfiguration supporting inhibitory control.

    Science.gov (United States)

    Spielberg, Jeffrey M; Miller, Gregory A; Heller, Wendy; Banich, Marie T

    2015-08-11

    The ability to inhibit distracting stimuli from interfering with goal-directed behavior is crucial for success in most spheres of life. Despite an abundance of studies examining regional brain activation, knowledge of the brain networks involved in inhibitory control remains quite limited. To address this critical gap, we applied graph theory tools to functional magnetic resonance imaging data collected while a large sample of adults (n = 101) performed a color-word Stroop task. Higher demand for inhibitory control was associated with restructuring of the global network into a configuration that was more optimized for specialized processing (functional segregation), more efficient at communicating the output of such processing across the network (functional integration), and more resilient to potential interruption (resilience). In addition, there were regional changes with right inferior frontal sulcus and right anterior insula occupying more central positions as network hubs, and dorsal anterior cingulate cortex becoming more tightly coupled with its regional subnetwork. Given the crucial role of inhibitory control in goal-directed behavior, present findings identifying functional network organization supporting inhibitory control have the potential to provide additional insights into how inhibitory control may break down in a wide variety of individuals with neurological or psychiatric difficulties.

  16. Electrical coupling between A17 cells enhances reciprocal inhibitory feedback to rod bipolar cells.

    Science.gov (United States)

    Elgueta, Claudio; Leroy, Felix; Vielma, Alex H; Schmachtenberg, Oliver; Palacios, Adrian G

    2018-02-15

    A17 amacrine cells are an important part of the scotopic pathway. Their synaptic varicosities receive glutamatergic inputs from rod bipolar cells (RBC) and release GABA onto the same RBC terminal, forming a reciprocal feedback that shapes RBC depolarization. Here, using patch-clamp recordings, we characterized electrical coupling between A17 cells of the rat retina and report the presence of strongly interconnected and non-coupled A17 cells. In coupled A17 cells, evoked currents preferentially flow out of the cell through GJs and cross-synchronization of presynaptic signals in a pair of A17 cells is correlated to their coupling degree. Moreover, we demonstrate that stimulation of one A17 cell can induce electrical and calcium transients in neighboring A17 cells, thus confirming a functional flow of information through electrical synapses in the A17 coupled network. Finally, blocking GJs caused a strong decrease in the amplitude of the inhibitory feedback onto RBCs. We therefore propose that electrical coupling between A17 cells enhances feedback onto RBCs by synchronizing and facilitating GABA release from inhibitory varicosities surrounding each RBC axon terminal. GJs between A17 cells are therefore critical in shaping the visual flow through the scotopic pathway.

  17. Pharmacological differences between memory consolidation of habituation to an open field and inhibitory avoidance learning

    Directory of Open Access Journals (Sweden)

    Vianna M.R.M.

    2001-01-01

    Full Text Available Rats implanted bilaterally with cannulae in the CA1 region of the dorsal hippocampus or the entorhinal cortex were submitted to either a one-trial inhibitory avoidance task, or to 5 min of habituation to an open field. Immediately after training, they received intrahippocampal or intraentorhinal 0.5-µl infusions of saline, of a vehicle (2% dimethylsulfoxide in saline, of the glutamatergic N-methyl-D-aspartate (NMDA receptor antagonist 2-amino-5-phosphono pentanoic acid (AP5, of the protein kinase A inhibitor Rp-cAMPs (0.5 µg/side, of the calcium-calmodulin protein kinase II inhibitor KN-62, of the dopaminergic D1 antagonist SCH23390, or of the mitogen-activated protein kinase kinase inhibitor PD098059. Animals were tested in each task 24 h after training. Intrahippocampal KN-62 was amnestic for habituation; none of the other treatments had any effect on the retention of this task. In contrast, all of them strongly affected memory of the avoidance task. Intrahippocampal Rp-cAMPs, KN-62 and AP5, and intraentorhinal Rp-cAMPs, KN-62, PD098059 and SCH23390 caused retrograde amnesia. In view of the known actions of the treatments used, the present findings point to important biochemical differences in memory consolidation processes of the two tasks.

  18. Inhibitory phenotype of HBV-specific CD4+ T-cells is characterized by high PD-1 expression but absent coregulation of multiple inhibitory molecules.

    Directory of Open Access Journals (Sweden)

    Bijan Raziorrouh

    Full Text Available T-cell exhaustion seems to play a critical role in CD8+ T-cell dysfunction during chronic viral infections. However, up to now little is known about the mechanisms underlying CD4+ T-cell dysfunction during chronic hepatitis B virus (CHB infection and the role of inhibitory molecules such as programmed death 1 (PD-1 for CD4+ T-cell failure.The expression of multiple inhibitory molecules such as PD-1, CTLA-4, TIM-3, CD244, KLRG1 and markers defining the grade of T-cell differentiation as CCR7, CD45RA, CD57 and CD127 were analyzed on virus-specific CD4+ T-cells from peripheral blood using a newly established DRB1*01-restricted MHC class II Tetramer. Effects of in vitro PD-L1/2 blockade were defined by investigating changes in CD4+ T-cell proliferation and cytokine production.CD4+ T-cell responses during chronic HBV infection was characterized by reduced Tetramer+CD4+ T-cell frequencies, effector memory phenotype, sustained PD-1 but low levels of CTLA-4, TIM-3, KLRG1 and CD244 expression. PD-1 blockade revealed individualized patterns of in vitro responsiveness with partly increased IFN-γ, IL-2 and TNF-α secretion as well as enhanced CD4+ T-cell expansion almost in treated patients with viral control.HBV-specific CD4+ T-cells are reliably detectable during different courses of HBV infection by MHC class II Tetramer technology. CD4+ T-cell dysfunction during chronic HBV is basically linked to strong PD-1 upregulation but absent coregulation of multiple inhibitory receptors. PD-L1/2 neutralization partly leads to enhanced CD4+ T-cell functionality with heterogeneous patterns of CD4+ T-cell rejunivation.

  19. Biophysical Insights into the Inhibitory Mechanism of Non-Nucleoside HIV-1 Reverse Transcriptase Inhibitors

    Directory of Open Access Journals (Sweden)

    Nicolas Sluis-Cremer

    2013-11-01

    Full Text Available HIV-1 reverse transcriptase (RT plays a central role in HIV infection. Current United States Federal Drug Administration (USFDA-approved antiretroviral therapies can include one of five approved non-nucleoside RT inhibitors (NNRTIs, which are potent inhibitors of RT activity. Despite their crucial clinical role in treating and preventing HIV-1 infection, their mechanism of action remains elusive. In this review, we introduce RT and highlight major advances from experimental and computational biophysical experiments toward an understanding of RT function and the inhibitory mechanism(s of NNRTIs.

  20. Fluctuating inhibitory inputs promote reliable spiking at theta frequencies in hippocampal interneurons

    Directory of Open Access Journals (Sweden)

    Duluxan eSritharan

    2012-05-01

    Full Text Available Theta frequency (4-12 Hz rhythms in the hippocampus play important roles in learning and memory. CA1 interneurons located at the stratum lacunosum-moleculare and radiatum junction (LM/RAD are thought to contribute to hippocampal theta population activities by rhythmically pacing pyramidal cells with inhibitory postsynaptic potentials. This implies that LM/RAD cells need to fire reliably at theta frequencies in vivo. To determine whether this could occur, we use biophysically-based LM/RAD model cells and apply different cholinergic and synaptic inputs to simulate in vivo-like network environments. We assess spike reliabilities and spiking frequencies, identifying biophysical properties and network conditions that best promote reliable theta spiking. We find that synaptic background activities that feature large inhibitory, but not excitatory, fluctuations are essential. This suggests that strong inhibitory input to these cells is vital for them to be able to contribute to population theta activities. Furthermore, we find that Type I-like oscillator models produced by augmented persistent sodium currents (INap or diminished A type potassium currents (IA enhance reliable spiking at lower theta frequencies. These Type I-like models are also the most responsive to large inhibitory fluctuations and can fire more reliably under such conditions. In previous work, we showed that INap and IA are largely responsible for establishing LM/RAD cells’ subthreshold activities. Taken together with this study, we see that while both these currents are important for subthreshold theta fluctuations and reliable theta spiking, they contribute in different ways – INap to reliable theta spiking and subthreshold activity generation, and IA to subthreshold activities at theta frequencies. This suggests that linking subthreshold and suprathreshold activities should be done with consideration of both in vivo contexts and biophysical specifics.

  1. Excitatory and inhibitory synaptic mechanisms at the first stage of integration in the electroreception system of the shark

    DEFF Research Database (Denmark)

    Rotem, Naama; Sestieri, Emanuel; Hounsgaard, Jørn Dybkjær

    2014-01-01

    High impulse rate in afferent nerves is a common feature in many sensory systems that serve to accommodate a wide dynamic range. However, the first stage of integration should be endowed with specific properties that enable efficient handling of the incoming information. In elasmobranches...... of this afferent pathway. We found that stimulating the afferent nerve activates a mixture of excitatory and inhibitory synapses mediated by AMPA-like and GABAA receptors, respectively. The excitatory synapses that are extremely efficient in activating the postsynaptic neurons display unusual voltage dependence......, enabling them to operate as a current source. The inhibitory input is powerful enough to completely eliminate the excitatory action of the afferent nerve but is ineffective regarding other excitatory inputs. These observations can be explained by the location and efficiency of the synapses. We conclude...

  2. Effect of polyunsaturated fatty acids and their metabolites on bleomycin-induced cytotoxic action on human neuroblastoma cells in vitro.

    Directory of Open Access Journals (Sweden)

    Sailaja Polavarapu

    Full Text Available In the present study, we noted that bleomycin induced growth inhibitory action was augmented by all the polyunsaturated fatty acids (PUFAs tested on human neuroblastoma IMR-32 (0.5 × 10(4 cells/100 µl of IMR cells (EPA > DHA > ALA = GLA = AA > DGLA = LA: ∼ 60, 40, 30, 10-20% respectively at the maximum doses used. Of all the prostaglandins (PGE1, PGE2, PGF2α, and PGI2 and leukotrienes (LTD4 and LTE4 tested; PGE1, PGE2 and LTD4 inhibited the growth of IMR-32 cells to a significant degree at the highest doses used. Lipoxin A4 (LXA4, 19,20-dihydroxydocosapentaenoate (19, 20 DiHDPA and 10(S,17(S-dihydroxy-4Z,7Z,11E,13Z,15E,19Z-docosahexaenoic acid (protectin: 10(S,17(SDiHDoHE, metabolites of DHA, significantly inhibited the growth of IMR-32 cells. Pre-treatment with AA, GLA, DGLA and EPA and simultaneous treatment with all PUFAs used in the study augmented growth inhibitory action of bleomycin. Surprisingly, both indomethacin and nordihydroguaiaretic acid (NDGA at 60 and 20 µg/ml respectively enhanced the growth of IMR-32 cells even in the presence of bleomycin. AA enhanced oxidant stress in IMR-32 cells as evidenced by an increase in lipid peroxides, superoxide dismutase levels and glutathione peroxidase activity. These results suggest that PUFAs suppress growth of human neuroblastoma cells, augment growth inhibitory action of bleomycin by enhancing formation of lipid peroxides and altering the status of anti-oxidants and, in all probability, increase the formation of lipoxins, resolvins and protectins from their respective precursors that possess growth inhibitory actions.

  3. Chemical Constituents of Malaysian U. cordata var. ferruginea and Their in Vitro α-Glucosidase Inhibitory Activities

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    Nur Hakimah Abdullah

    2016-04-01

    Full Text Available Continuing our interest in the Uncaria genus, the phytochemistry and the in-vitro α-glucosidase inhibitory activities of Malaysian Uncaria cordata var. ferruginea were investigated. The phytochemical study of this plant, which employed various chromatographic techniques including recycling preparative HPLC, led to the isolation of ten compounds with diverse structures comprising three phenolic acids, two coumarins, three flavonoids, a terpene and an iridoid glycoside. These constituents were identified as 2-hydroxybenzoic acid or salicylic acid (1, 2,4-dihydroxybenzoic acid (2, 3,4-dihydroxybenzoic acid (3, scopoletin or 7-hydroxy-6-methoxy-coumarin (4, 3,4-dihydroxy-7-methoxycoumarin (5, quercetin (6, kaempferol (7, taxifolin (8, loganin (9 and β-sitosterol (10. Structure elucidation of the compounds was accomplished with the aid of 1D and 2D Nuclear Magnetic Resonance (NMR spectral data and Ultraviolet-Visible (UV-Vis, Fourier Transform Infrared (FTIR spectroscopy and mass spectrometry (MS. In the α-glucosidase inhibitory assay, the crude methanolic extract of the stems of the plant and its acetone fraction exhibited strong α-glucosidase inhibition activity of 87.7% and 89.2%, respectively, while its DCM fraction exhibited only moderate inhibition (75.3% at a concentration of 1 mg/mL. The IC50 values of both fractions were found to be significantly lower than the standard acarbose suggesting the presence of potential α-glucosidase inhibitors. Selected compounds isolated from the active fractions were then subjected to α-glucosidase assay in which 2,4-dihydroxybenzoic acid and quercetin showed strong inhibitory effects against the enzyme with IC50 values of 549 and 556 μg/mL compared to acarbose (IC50 580 μg/mL while loganin and scopoletin only showed weak α-glucosidase inhibition of 44.9% and 34.5%, respectively. This is the first report of the isolation of 2-hydroxybenzoic acid, 2,4-dihydroxybenzoic acid and loganin from the genus

  4. Isolation of an inhibitory insulin-like growth factor (IGF) binding protein from bone cell-conditioned medium: A potential local regulator of IGF action

    International Nuclear Information System (INIS)

    Mohan, S.; Bautista, C.M.; Wergedal, J.; Baylink, D.J.

    1989-01-01

    Inhibitory insulin-like growth factor binding protein (In-IGF-BP) has been purified to homogeneity from medium conditioned by TE89 human osteosarcoma cells by two different methods using Sephadex G-100 gel filtration, FPLC Mono Q ion-exchange, HPLC C 4 reverse-phase, HPLC CN reverse-phase and affinity chromatographies. In-IGF-BP thus purified appeared to be homogeneous and unique by the following criteria. (i) N-terminal sequence analysis yielded a unique sequence (Asp-Glu-Ala-Ile-His-Cys-Pro-Pro-Glu-Ser-Glu-Ala-Lys-Leu-Ala). (ii) Amino acid composition of In-IGF-BP revealed marked differences with the amino acid compositions of other known PBs. (iii) In-IGF-BP exhibited a single band with molecular mass of 25 kDa under reducing conditions on sodium dodecyl sulfate/polyacrylamide gels. IGF-I and IGF-II but not insulin displaced the binding of 125 I-labeled IGF-I or 125 I-labeled IGF-II binding to In-IGF-BP. In-IGF-BP inhibited basal, IGF-stimulated bone cell proliferation and serum-stimulated bone cell proliferation. Forskolin increases synthesis of In-IGF-BP in TE85 human osteosarcoma cells in a dose-dependent manner. Based on these findings, the authors conclude that In-IGF-BP is a protein that has a unique sequence and significant biological actions on bone cells

  5. Short-term Synaptic Depression in the Feedforward Inhibitory Circuit in the Dorsal Lateral Geniculate Nucleus.

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    Augustinaite, Sigita; Heggelund, Paul

    2018-05-24

    Synaptic short-term plasticity (STP) regulates synaptic transmission in an activity-dependent manner and thereby has important roles in the signal processing in the brain. In some synapses, a presynaptic train of action potentials elicits post-synaptic potentials that gradually increase during the train (facilitation), but in other synapses, these potentials gradually decrease (depression). We studied STP in neurons in the visual thalamic relay, the dorsal lateral geniculate nucleus (dLGN). The dLGN contains two types of neurons: excitatory thalamocortical (TC) neurons, which transfer signals from retinal afferents to visual cortex, and local inhibitory interneurons, which form an inhibitory feedforward loop that regulates the thalamocortical signal transmission. The overall STP in the retino-thalamic relay is short-term depression, but the distinct kind and characteristics of the plasticity at the different types of synapses are unknown. We studied STP in the excitatory responses of interneurons to stimulation of retinal afferents, in the inhibitory responses of TC neurons to stimulation of afferents from interneurons, and in the disynaptic inhibitory responses of TC neurons to stimulation of retinal afferents. Moreover, we studied STP at the direct excitatory input to TC neurons from retinal afferents. The STP at all types of the synapses showed short-term depression. This depression can accentuate rapid changes in the stream of signals and thereby promote detectability of significant features in the sensory input. In vision, detection of edges and contours is essential for object perception, and the synaptic short-term depression in the early visual pathway provides important contributions to this detection process. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

  6. Electroacupuncture Potentiates Cannabinoid Receptor-Mediated Descending Inhibitory Control in a Mouse Model of Knee Osteoarthritis

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    Xiao-Cui Yuan

    2018-04-01

    Full Text Available Knee osteoarthritis (KOA is a highly prevalent, chronic joint disorder, which can lead to chronic pain. Although electroacupuncture (EA is effective in relieving chronic pain in the clinic, the involved mechanisms remain unclear. Reduced diffuse noxius inhibitory controls (DNIC function is associated with chronic pain and may be related to the action of endocannabinoids. In the present study, we determined whether EA may potentiate cannabinoid receptor-mediated descending inhibitory control and inhibit chronic pain in a mouse model of KOA. We found that the optimized parameters of EA inhibiting chronic pain were the low frequency and high intensity (2 Hz + 1 mA. EA reversed the reduced expression of CB1 receptors and the 2-arachidonoylglycerol (2-AG level in the midbrain in chronic pain. Microinjection of the CB1 receptor antagonist AM251 into the ventrolateral periaqueductal gray (vlPAG can reversed the EA effect on pain hypersensitivity and DNIC function. In addition, CB1 receptors on GABAergic but not glutamatergic neurons are involved in the EA effect on DNIC function and descending inhibitory control of 5-HT in the medulla, thus inhibiting chronic pain. Our data suggest that endocannabinoid (2-AG-CB1R-GABA-5-HT may be a novel signaling pathway involved in the effect of EA improving DNIC function and inhibiting chronic pain.

  7. Inhibitory potential of nine mentha species against pathogenic bacteria strains

    International Nuclear Information System (INIS)

    Hussain, A.; Ahmad, N.; Rashid, M.; Ikram, A. U.; Shinwari, Z. K.

    2015-01-01

    Plants produce secondary metabolites, which are used in their growth and defense against pathogenic agents. These plant based metabolites can be used as natural antibiotics against pathogenic bacteria. Synthetic antibiotics caused different side effects and become resistant to bacteria. Therefore the main objective of the present study was to investigate the inhibitory potential of nine Mentha species extracts against pathogenic bacteria. The methanolic leaves extracts of nine Mentha species (Mentha arvensis, Mentha longifolia, Mentha officinalis, Mentha piperita, Mentha citrata, Mentha pulegium, Mentha royleana, Mentha spicata and Mentha suareolens) were compared for antimicrobial activities. These Mentha species showed strong antibacterial activity against four microorganisms tested. Mentha arvensis showed 25 mm and 30 mm zones of inhibition against Staphylococcus aureus, Vibrio cholera and Enterobacter aerogens. Moreover, Mentha longifolia showed 24 mm zone of inhibition against Staphylococcus aureus. Mentha officinalis showed 30 mm zone of inhibition against Staphylococcus aureus. 25 mm inhibitory zone was recorded against Staphylococcus aureus by Mentha piperita. Mentha royleana showed 25 mm zone of inhibition against Vibrio cholera, while Mentha spicata showed 21 mm, 22 mm and 23 mm zones of inhibition against Staphylococcus aureus, Vibrio cholera and Enterobacter aerogens. Moreover most of the Mentha species showed zone of inhibition in the range of 10-20 mm. (author)

  8. Mechanism underlying unaltered cortical inhibitory synaptic transmission in contrast with enhanced excitatory transmission in CaV2.1 knockin migraine mice

    Science.gov (United States)

    Vecchia, Dania; Tottene, Angelita; van den Maagdenberg, Arn M.J.M.; Pietrobon, Daniela

    2014-01-01

    Familial hemiplegic migraine type 1 (FHM1), a monogenic subtype of migraine with aura, is caused by gain-of-function mutations in CaV2.1 (P/Q-type) calcium channels. In FHM1 knockin mice, excitatory neurotransmission at cortical pyramidal cell synapses is enhanced, but inhibitory neurotransmission at connected pairs of fast-spiking (FS) interneurons and pyramidal cells is unaltered, despite being initiated by CaV2.1 channels. The mechanism underlying the unaltered GABA release at cortical FS interneuron synapses remains unknown. Here, we show that the FHM1 R192Q mutation does not affect inhibitory transmission at autapses of cortical FS and other types of multipolar interneurons in microculture from R192Q knockin mice, and investigate the underlying mechanism. Lowering the extracellular [Ca2+] did not reveal gain-of-function of evoked transmission neither in control nor after prolongation of the action potential (AP) with tetraethylammonium, indicating unaltered AP-evoked presynaptic calcium influx at inhibitory autapses in FHM1 KI mice. Neither saturation of the presynaptic calcium sensor nor short duration of the AP can explain the unaltered inhibitory transmission in the mutant mice. Recordings of the P/Q-type calcium current in multipolar interneurons in microculture revealed that the current density and the gating properties of the CaV2.1 channels expressed in these interneurons are barely affected by the FHM1 mutation, in contrast with the enhanced current density and left-shifted activation gating of mutant CaV2.1 channels in cortical pyramidal cells. Our findings suggest that expression of specific CaV2.1 channels differentially sensitive to modulation by FHM1 mutations in inhibitory and excitatory cortical neurons underlies the gain-of-function of excitatory but unaltered inhibitory synaptic transmission and the likely consequent dysregulation of the cortical excitatory–inhibitory balance in FHM1. PMID:24907493

  9. Recruitment of activation receptors at inhibitory NK cell immune synapses.

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    Nicolas Schleinitz

    2008-09-01

    Full Text Available Natural killer (NK cell activation receptors accumulate by an actin-dependent process at cytotoxic immune synapses where they provide synergistic signals that trigger NK cell effector functions. In contrast, NK cell inhibitory receptors, including members of the MHC class I-specific killer cell Ig-like receptor (KIR family, accumulate at inhibitory immune synapses, block actin dynamics, and prevent actin-dependent phosphorylation of activation receptors. Therefore, one would predict inhibition of actin-dependent accumulation of activation receptors when inhibitory receptors are engaged. By confocal imaging of primary human NK cells in contact with target cells expressing physiological ligands of NK cell receptors, we show here that this prediction is incorrect. Target cells included a human cell line and transfected Drosophila insect cells that expressed ligands of NK cell activation receptors in combination with an MHC class I ligand of inhibitory KIR. The two NK cell activation receptors CD2 and 2B4 accumulated and co-localized with KIR at inhibitory immune synapses. In fact, KIR promoted CD2 and 2B4 clustering, as CD2 and 2B4 accumulated more efficiently at inhibitory synapses. In contrast, accumulation of KIR and of activation receptors at inhibitory synapses correlated with reduced density of the integrin LFA-1. These results imply that inhibitory KIR does not prevent CD2 and 2B4 signaling by blocking their accumulation at NK cell immune synapses, but by blocking their ability to signal within inhibitory synapses.

  10. Minocycline inhibits D-amphetamine-elicited action potential bursts in a central snail neuron.

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    Chen, Y-H; Lin, P-L; Wong, R-W; Wu, Y-T; Hsu, H-Y; Tsai, M-C; Lin, M-J; Hsu, Y-C; Lin, C-H

    2012-10-25

    Minocycline is a second-generation tetracycline that has been reported to have powerful neuroprotective properties. In our previous studies, we found that d-amphetamine (AMPH) elicited action potential bursts in an identifiable RP4 neuron of the African snail, Achatina fulica Ferussac. This study sought to determine the effects of minocycline on the AMPH-elicited action potential pattern changes in the central snail neuron, using the two-electrode voltage clamping method. Extracellular application of AMPH at 300 μM elicited action potential bursts in the RP4 neuron. Minocycline dose-dependently (300-900 μM) inhibited the action potential bursts elicited by AMPH. The inhibitory effects of minocycline on AMPH-elicited action potential bursts were restored by forskolin (50 μM), an adenylate cyclase activator, and by dibutyryl cAMP (N(6),2'-O-Dibutyryladenosine 3',5'-cyclic monophosphate; 1mM), a membrane-permeable cAMP analog. Co-administration of forskolin (50 μM) plus tetraethylammonium chloride (TEA; 5mM) or co-administration of TEA (5mM) plus dibutyryl cAMP (1mM) also elicited action potential bursts, which were prevented and inhibited by minocycline. In addition, minocycline prevented and inhibited forskolin (100 μM)-elicited action potential bursts. Notably, TEA (50mM)-elicited action potential bursts in the RP4 neuron were not affected by minocycline. Minocycline did not affect steady-state outward currents of the RP4 neuron. However, minocycline did decrease the AMPH-elicited steady-state current changes. Similarly, minocycline decreased the effects of forskolin-elicited steady-state current changes. Pretreatment with H89 (N-[2-(p-Bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide dihydrochloride; 10 μM), a protein kinase A inhibitor, inhibited AMPH-elicited action potential bursts and decreased AMPH-elicited steady-state current changes. These results suggest that the cAMP-protein kinase A signaling pathway and the steady-state current are involved in

  11. Virus-cell fusion inhibitory activity of novel analogue peptides based on the HP (2-20) derived from N-terminus of Helicobacter pylori Ribosomal Protein L1.

    Science.gov (United States)

    Woo, Eun-Rhan; Lee, Dong Gun; Chang, Young-Su; Park, Yoonkyung; Hahm, Kyung-Soo

    2002-12-01

    HP (2-20) (AKKVFKRLEKLFSKIQNDK) is the antibacterial sequence derived from N-terminus of Helicobacter pylori Ribosomal Protein L1 (RPL1). It has a broad-spectrum microbicidal activity in vitro that is thought to be related to the membrane-disruptive properties of the peptide. Based on the putative membrane-targeted mode of action, we postulated that HP (2-20) might be possessed virus-cell fusion inhibitory activity. To develop the novel virus-cell fusion inhibitory peptides, several analogues with amino acid substitution were designed to increase or decrease only net hydrophobic region. In particular, substitution of Gln and Asp for hydrophobic amino acid, Trp at position 17 and 19 of HP (2-20) (Anal 3) caused a dramatic increase in virus-cell fusion inhibitory activity without hemolytic effect.

  12. Anti-dengue virus serotype 2 activity and mode of action of a novel peptide.

    Science.gov (United States)

    Chew, M-F; Tham, H-W; Rajik, M; Sharifah, S H

    2015-10-01

    To identify a novel antiviral peptide against dengue virus serotype 2 (DENV-2) by screening a phage display peptide library and to evaluate its in vitro antiviral activity and mode of action. A phage display peptide library was biopanned against purified DENV-2 and resulted in the identification and selection of a peptide (peptide gg-ww) for further investigation. ELISA was performed, and peptide gg-ww was shown to possess the highest binding affinity against DENV-2. Thus, peptide gg-ww was synthesized for cytotoxicity and antiviral assays. Virus plaque reduction assay, real-time PCR and immunofluorescence assay were used to investigate the inhibitory effect of peptide gg-ww on DENV-2 infection in Vero cells. Three different assays (pre-, simultaneous and post-treatments assays) were performed to investigate the peptide's mode of action. Results indicated that peptide gg-ww possessed strong antiviral activity with a ~96% inhibition rate, which was achieved at 250 μmol l(-1) . Viral replication was inhibited during a simultaneous treatment assay, indicating that the entry of the virus was impeded by this peptide. Peptide gg-ww displayed antiviral action against DENV-2 by targeting an early stage of viral replication (i.e. during viral entry). Peptide gg-ww may represent a new therapeutic candidate for the treatment of DENV infections and is a potential candidate to be developed as a peptide drug. © 2015 The Society for Applied Microbiology.

  13. Fungicidal activities and mechanisms of action of Pseudomonas syringae pv. syringae lipodepsipeptide syringopeptins 22A and 25A

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    Mekki F. Bensaci

    2011-10-01

    Full Text Available The plant-associated bacterium Pseudomonas syringae pv. syringae simultaneously produces two classes of metabolites: the small cyclic lipodepsinonapeptides such as the syringomycins and the larger cyclic lipodepsipeptide syringopeptins SP22 or SP25. The syringomycins inhibit a broad spectrum of fungi (but particularly yeasts by lipid-dependent membrane interaction. The syringopeptins are phytotoxic and inhibitory to Gram positive bacteria. In this study, the fungicidal activities of two major syringopeptins, SP22A and SP25A, and their mechanisms of action were investigated and compared to those of syringomycin E. SP22A and SP25A were observed to inhibit the fungal yeasts Saccharomyces cerevisiae and Candida albicans although less effectively than syringomycin E. S. cerevisiae mutants defective in ergosterol and sphingolipid biosyntheses were less susceptible to SP22A and SP25A but the relative inhibitory capabilities of SRE vs. SP22A and SP25A were maintained. Similar differences were observed for capabilities to cause cellular K+ and Ca2+ fluxes in S. cerevisiae. Interestingly, in phospholipid bilayers the syringopeptins are found to induce larger macroscopic ionic conductances than syringomycin E but form single channels with similar properties. These findings suggest that the syringopeptins target the yeast plasma membrane, and, like syringomycin E, employ a lipid-dependent channel forming mechanism of action. The differing degrees of growth inhibition by these lipodepsipeptides may be explained by differences in their hydrophobicity. The more hydrophobic SP22A and SP25A might interact more strongly with the yeast cell wall that would create a selective barrier for their incorporation into the plasma membrane.

  14. Bilingual Contexts Modulate the Inhibitory Control Network

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    Jing Yang

    2018-03-01

    Full Text Available The present functional magnetic resonance imaging (fMRI study investigated influences of language contexts on inhibitory control and the underlying neural processes. Thirty Cantonese–Mandarin–English trilingual speakers, who were highly proficient in Cantonese (L1 and Mandarin (L2, and moderately proficient in English (L3, performed a picture-naming task in three dual-language contexts (L1-L2, L2-L3, and L1-L3. After each of the three naming tasks, participants performed a flanker task, measuring contextual effects on the inhibitory control system. Behavioral results showed a typical flanker effect in the L2-L3 and L1-L3 condition, but not in the L1-L2 condition, which indicates contextual facilitation on inhibitory control performance by the L1-L2 context. Whole brain analysis of the fMRI data acquired during the flanker tasks showed more neural activations in the right prefrontal cortex and subcortical areas in the L2-L3 and L1-L3 condition on one hand as compared to the L1-L2 condition on the other hand, suggesting greater involvement of the cognitive control areas when participants were performing the flanker task in L2-L3 and L1-L3 contexts. Effective connectivity analyses displayed a cortical-subcortical-cerebellar circuitry for inhibitory control in the trilinguals. However, contrary to the right-lateralized network in the L1-L2 condition, functional networks for inhibitory control in the L2-L3 and L1-L3 condition are less integrated and more left-lateralized. These findings provide a novel perspective for investigating the interaction between bilingualism (multilingualism and inhibitory control by demonstrating instant behavioral effects and neural plasticity as a function of changes in global language contexts.

  15. Chelation: A Fundamental Mechanism of Action of AGE Inhibitors, AGE Breakers, and Other Inhibitors of Diabetes Complications

    Energy Technology Data Exchange (ETDEWEB)

    Nagai, Rhoji; Murray, David B.; Metz, Thomas O.; Baynes, John

    2012-03-01

    Advanced glycation or glycoxidation end-products (AGE) increase in tissue proteins with age, and their rate of accumulation is increased in diabetes, nephropathy and inflammatory diseases. AGE inhibitors include a range of compounds that are proposed to act by trapping carbonyl and dicarbonyl intermediates in AGE formation. However, some among the newer generation of AGE inhibitors lack reactive functional groups that would trap reaction intermediates, indicating an alternative mechanism of action. We propose that AGE inhibitors function primarily as chelators, inhibiting metal-catalyzed oxidation reactions. The AGE-inhibitory activity of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers is also consistent with their chelating activity. Finally, compounds described as AGE breakers, or their hydrolysis products, also have strong chelating activity, suggesting that these compounds also act through their chelating activity. We conclude that chelation is the common, and perhaps the primary, mechanism of action of AGE inhibitors and breakers, and that chronic, mild chelation therapy should prove useful in treatment of diabetes and age-related diseases characterized by oxidative stress, inflammation and increased chemical modification of tissue proteins by advanced glycoxidation and lipoxidation end-products.

  16. Decorrelation of Neural-Network Activity by Inhibitory Feedback

    Science.gov (United States)

    Einevoll, Gaute T.; Diesmann, Markus

    2012-01-01

    Correlations in spike-train ensembles can seriously impair the encoding of information by their spatio-temporal structure. An inevitable source of correlation in finite neural networks is common presynaptic input to pairs of neurons. Recent studies demonstrate that spike correlations in recurrent neural networks are considerably smaller than expected based on the amount of shared presynaptic input. Here, we explain this observation by means of a linear network model and simulations of networks of leaky integrate-and-fire neurons. We show that inhibitory feedback efficiently suppresses pairwise correlations and, hence, population-rate fluctuations, thereby assigning inhibitory neurons the new role of active decorrelation. We quantify this decorrelation by comparing the responses of the intact recurrent network (feedback system) and systems where the statistics of the feedback channel is perturbed (feedforward system). Manipulations of the feedback statistics can lead to a significant increase in the power and coherence of the population response. In particular, neglecting correlations within the ensemble of feedback channels or between the external stimulus and the feedback amplifies population-rate fluctuations by orders of magnitude. The fluctuation suppression in homogeneous inhibitory networks is explained by a negative feedback loop in the one-dimensional dynamics of the compound activity. Similarly, a change of coordinates exposes an effective negative feedback loop in the compound dynamics of stable excitatory-inhibitory networks. The suppression of input correlations in finite networks is explained by the population averaged correlations in the linear network model: In purely inhibitory networks, shared-input correlations are canceled by negative spike-train correlations. In excitatory-inhibitory networks, spike-train correlations are typically positive. Here, the suppression of input correlations is not a result of the mere existence of correlations between

  17. Cadinane sesquiterpenes from Curcuma phaeocaulis with their inhibitory activities on nitric oxide production in RAW 264.7 cells.

    Science.gov (United States)

    Ma, Jianghao; Wang, Ying; Liu, Yue; Gao, Suyu; Ding, Liqin; Zhao, Feng; Chen, Lixia; Qiu, Feng

    2015-06-01

    Four new cadinane-type sesquiterpenes named phacadinanes A-D (1-4) were isolated from the rhizomes of Curcuma phaeocaulis. Their structures were elucidated by 1D and 2D NMR, as well as accurate mass measurements. Compound 4 was the first example of a rare 4,5-seco-cadinane sesquiterpene isolated from the Zingiberaceae family. Furthermore, inhibitory effects of the isolated compounds on nitric oxide production in LPS-activated macrophages were evaluated. Compounds 1 and 2 showed strong inhibitory activities on NO production with IC50 values of 3.88±0.58 and 2.25±0.71 μM, respectively. A possible biogenetic pathway for 4,5-seco-cadinane sesquiterpene (4) was postulated. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Somatostatin-expressing inhibitory interneurons in cortical circuits

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    Iryna Yavorska

    2016-09-01

    Full Text Available Cortical inhibitory neurons exhibit remarkable diversity in their morphology, connectivity, and synaptic properties. Here, we review the function of somatostatin-expressing (SOM inhibitory interneurons, focusing largely on sensory cortex. SOM neurons also comprise a number of subpopulations that can be distinguished by their morphology, input and output connectivity, laminar location, firing properties, and expression of molecular markers. Several of these classes of SOM neurons show unique dynamics and characteristics, such as facilitating synapses, specific axonal projections, intralaminar input, and top-down modulation, which suggest possible computational roles. SOM cells can be differentially modulated by behavioral state depending on their class, sensory system, and behavioral paradigm. The functional effects of such modulation have been studied with optogenetic manipulation of SOM cells, which produces effects on learning and memory, task performance, and the integration of cortical activity. Different classes of SOM cells participate in distinct disinhibitory circuits with different inhibitory partners and in different cortical layers. Through these disinhibitory circuits, SOM cells help encode the behavioral relevance of sensory stimuli by regulating the activity of cortical neurons based on subcortical and intracortical modulatory input. Associative learning leads to long-term changes in the strength of connectivity of SOM cells with other neurons, often influencing the strength of inhibitory input they receive. Thus despite their heterogeneity and variability across cortical areas, current evidence shows that SOM neurons perform unique neural computations, forming not only distinct molecular but also functional subclasses of cortical inhibitory interneurons.

  19. Mutation of the inhibitory ethanol site in GABAA ρ1 receptors promotes tolerance to ethanol-induced motor incoordination.

    Science.gov (United States)

    Blednov, Yuri A; Borghese, Cecilia M; Ruiz, Carlos I; Cullins, Madeline A; Da Costa, Adriana; Osterndorff-Kahanek, Elizabeth A; Homanics, Gregg E; Harris, R Adron

    2017-09-01

    Genes encoding the ρ1/2 subunits of GABA A receptors have been associated with alcohol (ethanol) dependence in humans, and ρ1 was also shown to regulate some of the behavioral effects of ethanol in animal models. Ethanol inhibits GABA-mediated responses in wild-type (WT) ρ1, but not ρ1(T6'Y) mutant receptors expressed in Xenopus laevis oocytes, indicating the presence of an inhibitory site for ethanol in the second transmembrane helix. In this study, we found that ρ1(T6'Y) receptors expressed in oocytes display overall normal responses to GABA, the endogenous GABA modulator (zinc), and partial agonists (β-alanine and taurine). We generated ρ1 (T6'Y) knockin (KI) mice using CRISPR/Cas9 to test the behavioral importance of the inhibitory actions of ethanol on this receptor. Both ρ1 KI and knockout (KO) mice showed faster recovery from acute ethanol-induced motor incoordination compared to WT mice. Both KI and KO mutant strains also showed increased tolerance to motor impairment produced by ethanol. The KI mice did not differ from WT mice in other behavioral actions, including ethanol intake and preference, conditioned taste aversion to ethanol, and duration of ethanol-induced loss of righting reflex. WT and KI mice did not differ in levels of ρ1 or ρ2 mRNA in cerebellum or in ethanol clearance. Our findings indicate that the inhibitory site for ethanol in GABA A ρ1 receptors regulates acute functional tolerance to moderate ethanol intoxication. We note that low sensitivity to alcohol intoxication has been linked to risk for development of alcohol dependence in humans. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Do detour tasks provide accurate assays of inhibitory control?

    Science.gov (United States)

    Whiteside, Mark A.; Laker, Philippa R.; Beardsworth, Christine E.

    2018-01-01

    Transparent Cylinder and Barrier tasks are used to purportedly assess inhibitory control in a variety of animals. However, we suspect that performances on these detour tasks are influenced by non-cognitive traits, which may result in inaccurate assays of inhibitory control. We therefore reared pheasants under standardized conditions and presented each bird with two sets of similar tasks commonly used to measure inhibitory control. We recorded the number of times subjects incorrectly attempted to access a reward through transparent barriers, and their latencies to solve each task. Such measures are commonly used to infer the differential expression of inhibitory control. We found little evidence that their performances were consistent across the two different Putative Inhibitory Control Tasks (PICTs). Improvements in performance across trials showed that pheasants learned the affordances of each specific task. Critically, prior experience of transparent tasks, either Barrier or Cylinder, also improved subsequent inhibitory control performance on a novel task, suggesting that they also learned the general properties of transparent obstacles. Individual measures of persistence, assayed in a third task, were positively related to their frequency of incorrect attempts to solve the transparent inhibitory control tasks. Neophobia, Sex and Body Condition had no influence on individual performance. Contrary to previous studies of primates, pheasants with poor performance on PICTs had a wider dietary breadth assayed using a free-choice task. Our results demonstrate that in systems or taxa where prior experience and differences in development cannot be accounted for, individual differences in performance on commonly used detour-dependent PICTS may reveal more about an individual's prior experience of transparent objects, or their motivation to acquire food, than providing a reliable measure of their inhibitory control. PMID:29593115

  1. Organizers of inhibitory synapses come of age.

    Science.gov (United States)

    Krueger-Burg, Dilja; Papadopoulos, Theofilos; Brose, Nils

    2017-08-01

    While the postsynaptic density of excitatory synapses is known to encompass a highly complex molecular machinery, the equivalent organizational structure of inhibitory synapses has long remained largely undefined. In recent years, however, substantial progress has been made towards identifying the full complement of organizational proteins present at inhibitory synapses, including submembranous scaffolds, intracellular signaling proteins, transsynaptic adhesion proteins, and secreted factors. Here, we summarize these findings and discuss future challenges in assigning synapse-specific functions to the newly discovered catalog of proteins, an endeavor that will depend heavily on newly developed technologies such as proximity biotinylation. Further advances are made all the more essential by growing evidence that links inhibitory synapses to psychiatric and neurological disorders. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Antiobesity and Antidiabetes Effects of a Cudrania tricuspidata Hydrophilic Extract Presenting PTP1B Inhibitory Potential

    Directory of Open Access Journals (Sweden)

    Dae Hoon Kim

    2016-01-01

    Full Text Available Diabetes and obesity represent the major health problems and the most age-related metabolic diseases. Protein-tyrosine phosphatase 1B (PTP1B has emerged as an important regulator of insulin signal transduction and is regarded as a pharmaceutical target for metabolic disorders. To find novel natural materials presenting therapeutic activities against diabetes and obesity, we screened various herb extracts using a chip screening allowing the determination of PTP1B inhibitory effects of the tested compounds using insulin receptor (IR as the substrate. Cudrania tricuspidata leaves (CTe had a strong inhibitory effect on PTP1B activity and substantially inhibited fat accumulation in 3T3-L1 cells. CTe was orally administrated to diet-induced obesity (DIO mice once daily for 3 weeks after which changes in glucose, insulin metabolism, and fat accumulation were examined. Hepatic enzyme markers (aspartate aminotransferase, AST, and alanine aminotransferase, ALT and total fat mass and triglyceride levels decreased in CTe-treated mice, whereas body weight and total cholesterol concentration slightly decreased. CTe increased the phosphorylation of IRS-1 and Akt in liver tissue. Furthermore, CTe treatment significantly lowered blood glucose levels and improved insulin secretion in DIO mice. Our results strongly suggest that CTe may represent a promising therapeutic substance against diabetes and obesity.

  3. Antiobesity and Antidiabetes Effects of a Cudrania tricuspidata Hydrophilic Extract Presenting PTP1B Inhibitory Potential

    Science.gov (United States)

    Kim, Dae Hoon; Lee, Sooung; Chung, Youn Wook; Kim, Byeong Mo; Kim, Hanseul; Kim, Kunhong; Yang, Kyung Mi

    2016-01-01

    Diabetes and obesity represent the major health problems and the most age-related metabolic diseases. Protein-tyrosine phosphatase 1B (PTP1B) has emerged as an important regulator of insulin signal transduction and is regarded as a pharmaceutical target for metabolic disorders. To find novel natural materials presenting therapeutic activities against diabetes and obesity, we screened various herb extracts using a chip screening allowing the determination of PTP1B inhibitory effects of the tested compounds using insulin receptor (IR) as the substrate. Cudrania tricuspidata leaves (CTe) had a strong inhibitory effect on PTP1B activity and substantially inhibited fat accumulation in 3T3-L1 cells. CTe was orally administrated to diet-induced obesity (DIO) mice once daily for 3 weeks after which changes in glucose, insulin metabolism, and fat accumulation were examined. Hepatic enzyme markers (aspartate aminotransferase, AST, and alanine aminotransferase, ALT) and total fat mass and triglyceride levels decreased in CTe-treated mice, whereas body weight and total cholesterol concentration slightly decreased. CTe increased the phosphorylation of IRS-1 and Akt in liver tissue. Furthermore, CTe treatment significantly lowered blood glucose levels and improved insulin secretion in DIO mice. Our results strongly suggest that CTe may represent a promising therapeutic substance against diabetes and obesity. PMID:26989693

  4. Defining the Timing of Action of Antimalarial Drugs against Plasmodium falciparum

    Science.gov (United States)

    Langer, Christine; Goodman, Christopher D.; McFadden, Geoffrey I.

    2013-01-01

    Most current antimalarials for treatment of clinical Plasmodium falciparum malaria fall into two broad drug families and target the food vacuole of the trophozoite stage. No antimalarials have been shown to target the brief extracellular merozoite form of blood-stage malaria. We studied a panel of 12 drugs, 10 of which have been used extensively clinically, for their invasion, schizont rupture, and growth-inhibitory activity using high-throughput flow cytometry and new approaches for the study of merozoite invasion and early intraerythrocytic development. Not surprisingly, given reported mechanisms of action, none of the drugs inhibited merozoite invasion in vitro. Pretreatment of erythrocytes with drugs suggested that halofantrine, lumefantrine, piperaquine, amodiaquine, and mefloquine diffuse into and remain within the erythrocyte and inhibit downstream growth of parasites. Studying the inhibitory activity of the drugs on intraerythrocytic development, schizont rupture, and reinvasion enabled several different inhibitory phenotypes to be defined. All drugs inhibited parasite replication when added at ring stages, but only artesunate, artemisinin, cycloheximide, and trichostatin A appeared to have substantial activity against ring stages, whereas the other drugs acted later during intraerythrocytic development. When drugs were added to late schizonts, only artemisinin, cycloheximide, and trichostatin A were able to inhibit rupture and subsequent replication. Flow cytometry proved valuable for in vitro assays of antimalarial activity, with the free merozoite population acting as a clear marker for parasite growth inhibition. These studies have important implications for further understanding the mechanisms of action of antimalarials, studying and evaluating drug resistance, and developing new antimalarials. PMID:23318799

  5. A pilot investigation of acute inhibitory control training in cocaine users.

    Science.gov (United States)

    Alcorn, Joseph L; Pike, Erika; Stoops, William S; Lile, Joshua A; Rush, Craig R

    2017-05-01

    Disrupted response inhibition and presence of drug-cue attentional bias in cocaine-using individuals have predicted poor treatment outcomes. Inhibitory control training could help improve treatment outcomes by strengthening cognitive control. This pilot study assessed the effects of acute inhibitory control training to drug- and non-drug-related cues on response inhibition performance and cocaine-cue attentional bias in cocaine-using individuals. Participants who met criteria for a cocaine-use disorder underwent five sessions of inhibitory control training to either non-drug-related cues (i.e., rectangles) or cocaine cues (n=10/condition) in a single day. Response inhibition and attentional bias were assessed prior to and following training using the stop-signal task and visual-probe task with eye tracking, respectively. Training condition groups did not differ on demographics, inhibitory control training performance, response inhibition, or cocaine-cue attentional bias. Response inhibition performance improved as a function of inhibitory control training in both conditions. Cocaine-cue attentional bias was observed, but did not change as a function of inhibitory control training in either condition. Response inhibition in cocaine-using individuals was augmented by acute inhibitory control training, which may improve treatment outcomes through better behavioral inhibition. Future studies should investigate longer-term implementation of inhibitory control training, as well as combining inhibitory control training with other treatment modalities. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Inhibitory ability of children with developmental dyscalculia.

    Science.gov (United States)

    Zhang, Huaiying; Wu, Hanrong

    2011-02-01

    Inhibitory ability of children with developmental dyscalculia (DD) was investigated to explore the cognitive mechanism underlying DD. According to the definition of developmental dyscalculia, 19 children with DD-only and 10 children with DD&RD (DD combined with reading disability) were selected step by step, children in two control groups were matched with children in case groups by gender and age, and the match ratio was 1:1. Psychological testing software named DMDX was used to measure inhibitory ability of the subjects. The differences of reaction time in number Stroop tasks and differences of accuracy in incongruent condition of color-word Stroop tasks and object inhibition tasks between DD-only children and their controls reached significant levels (P<0.05), and the differences of reaction time in number Stroop tasks between dyscalculic and normal children did not disappear after controlling the non-executive components. The difference of accuracy in color-word incongruent tasks between children with DD&RD and normal children reached significant levels (P<0.05). Children with DD-only confronted with general inhibitory deficits, while children with DD&RD confronted with word inhibitory deficits only.

  7. Dissociating the role of prefrontal and premotor cortices in controlling inhibitory mechanisms during motor preparation.

    Science.gov (United States)

    Duque, Julie; Labruna, Ludovica; Verset, Sophie; Olivier, Etienne; Ivry, Richard B

    2012-01-18

    Top-down control processes are critical to select goal-directed actions in flexible environments. In humans, these processes include two inhibitory mechanisms that operate during response selection: one is involved in solving a competition between different response options, the other ensures that a selected response is initiated in a timely manner. Here, we evaluated the role of dorsal premotor cortex (PMd) and lateral prefrontal cortex (LPF) of healthy subjects in these two forms of inhibition by using an innovative transcranial magnetic stimulation (TMS) protocol combining repetitive TMS (rTMS) over PMd or LPF and a single pulse TMS (sTMS) over primary motor cortex (M1). sTMS over M1 allowed us to assess inhibitory changes in corticospinal excitability, while rTMS was used to produce transient disruption of PMd or LPF. We found that rTMS over LPF reduces inhibition associated with competition resolution, whereas rTMS over PMd decreases inhibition associated with response impulse control. These results emphasize the dissociable contributions of these two frontal regions to inhibitory control during motor preparation. The association of LPF with competition resolution is consistent with the role of this area in relatively abstract aspects of control related to goal maintenance, ensuring that the appropriate response is selected in a variable context. In contrast, the association of PMd with impulse control is consistent with the role of this area in more specific processes related to motor preparation and initiation.

  8. Dissociating the role of prefrontal and premotor cortices in controlling inhibitory mechanisms during motor preparation

    Science.gov (United States)

    Duque, Julie; Labruna, Ludovica; Verset, Sophie; Olivier, Etienne; Ivry, Richard B.

    2012-01-01

    Top-down control processes are critical to select goal-directed actions in flexible environments. In humans, these processes include two inhibitory mechanisms that operate during response selection: one is involved in solving a competition between different response options, the other ensures that a selected response is initiated timely. Here, we evaluated the role of dorsal premotor cortex (PMd) and lateral prefrontal cortex (LPF) of healthy subjects in these two forms of inhibition by using an innovative transcranial magnetic stimulation (TMS) protocol combining repetitive TMS (rTMS) over PMd or LPF and a single pulse TMS (sTMS) over primary motor cortex (M1). sTMS over M1 allowed us to assess inhibitory changes in corticospinal excitability, while rTMS was used to produce transient disruption of PMd or LPF. We found that rTMS over LPF reduces inhibition associated with competition resolution whereas rTMS over PMd decreases inhibition associated with response impulse control. These results emphasize the dissociable contributions of these two frontal regions to inhibitory control during motor preparation. The association of LPF with competition resolution is consistent with the role of this area in relatively abstract aspects of control related to goal maintenance, ensuring that the appropriate response is selected in a variable context. In contrast, the association of PMd with impulse control is consistent with the role of this area in more specific processes related to motor preparation and initiation. PMID:22262879

  9. [Effects of dauricine on action potentials and slow inward currents of guinea pig ventricular papillary muscles].

    Science.gov (United States)

    Li, S N; Zhang, K Y

    1992-11-01

    Effects of dauricine (Dau) on the action potentials (AP), the slow action potentials (SAP), and the slow inward currents (Isi) of guinea pig ventricular papillary muscles were observed by means of intracellular microelectrode and single sucrose gap voltage clamp technique. In the early stage, Dau shortened action potential duration 100 (APD100) and effective refractory period (ERP) (ERP/APD ERP, and APD20, significantly decreased action potential amplitude (APA), maximum velocity (Vmax), and overshot (OS) (ERP/APD > 1; P SAP induced by isoprenaline (P < 0.01), and remarkably inhibited Isi (P < 0.01). The results suggested that Dau exerted an inhibitory effect on Na+, Ca2+, and K+ channels.

  10. Kinetics of α-amylase and α-glucosidase inhibitory potential of Zea mays Linnaeus (Poaceae), Stigma maydis aqueous extract: An in vitro assessment.

    Science.gov (United States)

    Sabiu, S; O'Neill, F H; Ashafa, A O T

    2016-05-13

    Corn silk (Zea mays L., Stigma maydis) is an important herb used traditionally in many parts of the world to treat array of diseases including diabetes mellitus. Inhibitors of α-amylase and α-glucosidase offer an effective strategy to modulate levels of post prandial hyperglycaemia via control of starch metabolism. This study evaluated α-amylase and α-glucosidase inhibitory potentials of corn silk aqueous extract. Active principles and antioxidant attributes of the extract were also analysed. The α-amylase inhibitory potential of the extract was investigated by reacting its different concentrations with α-amylase and starch solution, while α-glucosidase inhibition was determined by pre-incubating α-glucosidase with different concentrations of the extract followed by addition of p-nitrophenylglucopyranoside. The mode(s) of inhibition of the enzymes were determined using Lineweaver-Burke plot. In vitro analysis of the extract showed that it exhibited potent and moderate inhibitory potential against α-amylase and α-glucosidase, respectively. The inhibition was concentration-dependent with respective half-maximal inhibitory concentration (IC50) values of 5.89 and 0.93mg/mL. Phytochemical analyses revealed the presence of alkaloids, flavonoids, phenols, saponins, tannins and phytosterols as probable inhibitory constituents. Furthermore, the extract remarkably scavenges reactive oxygen species like DPPH and nitric oxide radicals, elicited good reducing power and a significant metal chelating attributes. Overall, the non-competitive and uncompetitive mechanism of action of corn silk extract is due to its inhibitory effects on α-amylase and α-glucosidase, respectively. Consequently, this will reduce the rate of starch hydrolysis, enhance palliated glucose levels, and thus, lending credence to hypoglycaemic candidature of corn silk. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  11. Inhibition of α-Amylases by Condensed and Hydrolysable Tannins: Focus on Kinetics and Hypoglycemic Actions

    Directory of Open Access Journals (Sweden)

    Camila Gabriel Kato

    2017-01-01

    Full Text Available The aim of the present study was to compare the in vitro inhibitory effects on the salivary and pancreatic α-amylases and the in vivo hypoglycemic actions of the hydrolysable tannin from Chinese natural gall and the condensed tannin from Acacia mearnsii. The human salivary α-amylase was more strongly inhibited by the hydrolysable than by the condensed tannin, with the concentrations for 50% inhibition (IC50 being 47.0 and 285.4 μM, respectively. The inhibitory capacities of both tannins on the pancreatic α-amylase were also different, with IC50 values being 141.1 μM for the hydrolysable tannin and 248.1 μM for the condensed tannin. The kinetics of the inhibition presented complex patterns in that for both inhibitors more than one molecule can bind simultaneously to either the free enzyme of the substrate-complexed enzyme (parabolic mixed inhibition. Both tannins were able to inhibit the intestinal starch absorption. Inhibition by the hydrolysable tannin was concentration-dependent, with 53% inhibition at the dose of 58.8 μmol/kg and 88% inhibition at the dose of 294 μmol/kg. For the condensed tannin, inhibition was not substantially different for doses between 124.4 μmol/kg (49% and 620 μmol/kg (57%. It can be concluded that both tannins, but especially the hydrolysable one, could be useful in controlling the postprandial glycemic levels in diabetes.

  12. Strong cellulase inhibition by Mannan polysaccharides in cellulose conversion to sugars.

    Science.gov (United States)

    Kumar, Rajeev; Wyman, Charles E

    2014-07-01

    Cellulase enzymes contribute a major fraction of the total cost for biological conversion of lignocellulosic biomass to fuels and chemicals. Although a several fold reduction in cellulase production costs and enhancement of cellulase activity and stability have been reported in recent years, sugar yields are still lower at low enzyme doses than desired commercially. We recently reported that hemicellulose xylan and its oligomers strongly inhibit cellulase and that supplementation of cellulase with xylanase and β-xylosidase would significantly reduce such inhibition. In this study, mannan polysaccharides and their enzymatically prepared hydrolyzates were discovered to be strongly inhibitory to fungal cellulase in cellulose conversion (>50% drop in % relative conversion), even at a small concentration of 0.1 g/L, and inhibition was much greater than experienced by other known inhibitors such as cellobiose, xylooligomers, and furfural. Furthermore, cellulase inhibition dramatically increased with heteromannan loading and mannan substitution with galactose side units. In general, enzymatically prepared hydrolyzates were less inhibitory than their respective mannan polysaccharides except highly substituted ones. Supplementation of cellulase with commercial accessory enzymes such as xylanase, pectinase, and β-glucosidase was effective in greatly relieving inhibition but only for less substituted heteromannans. However, cellulase supplementation with purified heteromannan specific enzymes relieved inhibition by these more substituted heteromannans as well, suggesting that commercial preparations need to have higher amounts of such activities to realize high sugar yields at the low enzyme protein loadings needed for low cost fuels production. © 2014 Wiley Periodicals, Inc.

  13. Inhibitory effects of flavonoids on biofilm formation by Staphylococcus aureus that overexpresses efflux protein genes.

    Science.gov (United States)

    Lopes, Laênia Angélica Andrade; Dos Santos Rodrigues, Jéssica Bezerra; Magnani, Marciane; de Souza, Evandro Leite; de Siqueira-Júnior, José P

    2017-06-01

    This study evaluated the efficacy of glycone (myricitrin, hesperidin and phloridzin) and aglycone flavonoids (myricetin, hesperetin and phloretin) in inhibiting biofilm formation by Staphylococcus aureus RN4220 and S. aureus SA1199B that overexpress the msrA and norA efflux protein genes, respectively. The minimum inhibitory concentration (MIC) and minimum biofilm inhibitory concentration (MBIC 50 - defined as the lowest concentration that resulted in ≥50% inhibition of biofilm formation) of flavonoids were determined using microdilution in broth procedures. The flavonoids showed MIC >1024 μg/mL against S. aureus RN4220 and S. aureus SA1199B; however, these compounds at lower concentrations (1-256 μg/mL) showed inhibitory effects on biofilm formation by these strains. Aglycone flavonoids showed lower MBIC 50 values than their respective glycone forms. The lowest MBIC 50 values (1 and 4 μg/mL) were observed against S. aureus RN4220. Myricetin, hesperetin and phloretin exhibited biofilm formation inhibition >70% for S. aureus RN4220, and lower biofilm formation inhibition against S. aureus SA1199B. These results indicate that sub-MICs of the tested flavonoids inhibit biofilm formation by S. aureus strains that overexpress efflux protein genes. These effects are more strongly established by aglycone flavonoids. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Easy to learn, hard to suppress: The impact of learned stimulus-outcome associations on subsequent action control

    NARCIS (Netherlands)

    van Wouwe, N.C.; van den Wildenberg, W.P.M.; Ridderinkhof, K.R.; Claassen, D.O.; Neimat, J.S.; Wylie, S.A.

    2015-01-01

    The inhibition of impulsive response tendencies that conflict with goal-directed action is a key component of executive control. An emerging literature reveals that the proficiency of inhibitory control is modulated by expected or unexpected opportunities to earn reward or avoid punishment. However,

  15. Action video game training reduces the Simon Effect.

    Science.gov (United States)

    Hutchinson, Claire V; Barrett, Doug J K; Nitka, Aleksander; Raynes, Kerry

    2016-04-01

    A number of studies have shown that training on action video games improves various aspects of visual cognition including selective attention and inhibitory control. Here, we demonstrate that action video game play can also reduce the Simon Effect, and, hence, may have the potential to improve response selection during the planning and execution of goal-directed action. Non-game-players were randomly assigned to one of four groups; two trained on a first-person-shooter game (Call of Duty) on either Microsoft Xbox or Nintendo DS, one trained on a visual training game for Nintendo DS, and a control group who received no training. Response times were used to contrast performance before and after training on a behavioral assay designed to manipulate stimulus-response compatibility (the Simon Task). The results revealed significantly faster response times and a reduced cost of stimulus-response incompatibility in the groups trained on the first-person-shooter game. No benefit of training was observed in the control group or the group trained on the visual training game. These findings are consistent with previous evidence that action game play elicits plastic changes in the neural circuits that serve attentional control, and suggest training may facilitate goal-directed action by improving players' ability to resolve conflict during response selection and execution.

  16. Gonadotropin Inhibitory Hormone Down-Regulates the Brain-Pituitary Reproductive Axis of Male European Sea Bass (Dicentrarchus labrax).

    Science.gov (United States)

    Paullada-Salmerón, José A; Cowan, Mairi; Aliaga-Guerrero, María; Morano, Francesca; Zanuy, Silvia; Muñoz-Cueto, José A

    2016-06-01

    Gonadotropin-inhibitory hormone (GnIH) inhibits gonadotropin synthesis and release from the pituitary of birds and mammals. However, the physiological role of orthologous GnIH peptides on the reproductive axis of fish is still uncertain, and their actions on the main neuroendocrine systems controlling reproduction (i.e., GnRHs, kisspeptins) have received little attention. In a recent study performed in the European sea bass, we cloned a cDNA encoding a precursor polypeptide that contained C-terminal MPMRFamide (sbGnIH-1) and MPQRFamide (sbGnIH-2) peptide sequences, developed a specific antiserum against sbGnIH-2, and characterized its central and pituitary GnIH projections in this species. In this study, we analyzed the effects of intracerebroventricular injection of sbGnIH-1 and sbGnIH-2 on brain and pituitary expression of reproductive hormone genes (gnrh1, gnrh2, gnrh3, kiss1, kiss2, gnih, lhbeta, fshbeta), and their receptors (gnrhr II-1a, gnrhr II-2b, kiss1r, kiss2r, and gnihr) as well as on plasma Fsh and Lh levels. In addition, we determined the effects of GnIH on pituitary somatotropin (Gh) expression. The results obtained revealed the inhibitory role of sbGnIH-2 on brain gnrh2, kiss1, kiss2, kiss1r, gnih, and gnihr transcripts and on pituitary fshbeta, lhbeta, gh, and gnrhr-II-1a expression, whereas sbGnIH-1 only down-regulated brain gnrh1 expression. However, at different doses, central administration of both sbGnIH-1 and sbGnIH-2 decreased Lh plasma levels. Our work represents the first study reporting the effects of centrally administered GnIH in fish and provides evidence of the differential actions of sbGnIH-1 and sbGnIH-2 on the reproductive axis of sea bass, the main inhibitory role being exerted by the sbGnIH-2 peptide. © 2016 by the Society for the Study of Reproduction, Inc.

  17. Resveratrol exhibits a strong cytotoxic activity in cultured cells and has an antiviral action against polyomavirus: potential clinical use

    Directory of Open Access Journals (Sweden)

    Galati Gaspare

    2009-07-01

    Full Text Available Abstract Background Resveratrol is a non flavonoid polyphenol compound present in many plants and fruits and, at especially high concentrations, in the grape berries of Vitis vinifera. This compound has a strong bioactivity and its cytoprotective action has been demonstrated, however at high concentrations the drug exhibits also an effective anti-proliferative action. We recently showed its ability to abolish the effects of oxidative stress in cultured cells. In this work we assayed the bioactivity of resveratrol as antiproliferative and antiviral drug in cultured fibroblasts. Studies by other Authors showed that this natural compound inhibits the proliferation of different viruses such as herpes simplex, varicella-zoster and influenza A. The results presented here show an evident toxic activity of the drug at high concentrations, on the other hand at sub-cytotoxic concentrations, resveratrol can effectively inhibit the synthesis of polyomavirus DNA. A possible interpretation is that, due to the damage caused by resveratrol to the plasma membrane, the transfer of the virus from the endoplasmic reticulum to the nucleus, may be hindered thus inhibiting the production of viral DNA. Methods The mouse fibroblast line 3T6 and the human tumor line HL60 were used throughout the work. Cell viability and vital cell count were assessed respectively, by the MTT assay and Trypan Blue staining. Cytotoxic properties and evaluation of viral DNA production by agarose gel electrophoresis were performed according to standard protocols. Results Our results show a clear dose dependent both cytotoxic and antiviral effect of resveratrol respectively at high and low concentrations. The cytotoxic action is exerted towards a stabilized cell-line (3T6 as well as a tumor-line (HL60. Furthermore the antiviral action is evident after the phase of virion entry, therefore data suggest that the drug acts during the synthesis of the viral progeny DNA. Conclusion Resveratrol is

  18. Evaluation of the Antibacterial Effects and Mechanism of Action of Protocatechualdehyde against Ralstonia solanacearum

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    Shili Li

    2016-06-01

    Full Text Available Protocatechualdehyde (PCA is an important plant-derived natural product that has been associated with a wide variety of biological activities and has been widely used in medicine as an antioxidant, anti-aging and an anti-inflammatory agent. However, fewer reports concerning its antibacterial effects on plant-pathogenic bacteria exist. Therefore, in this study, protocatechualdehyde was evaluated for its antibacterial activity against plant pathogens along with the mechanism of its antibacterial action. PCA at 40 μg/mL was highly active against R. solanacearum and significantly inhibited its growth. The minimum bactericidal concentration and minimum inhibitory concentration values for PCA were 40 μg/mL and 20 μg/mL, respectively. Further investigation of the mechanism of action of PCA via transmission electron microscopy and biological assays indicated that the destruction of the cell structure, the shapes and the inhibition of biofilm formation were important. In addition, the application of PCA effectively reduced the incidence of bacterial wilt on tobacco under greenhouse conditions, and the control efficiency was as high as 92.01% at nine days after inoculation. Taken together, these findings suggest that PCA exhibits strong antibacterial activity against R. solanacearum and has the potential to be applied as an effective antibacterial agent for controlling bacterial wilt caused by R. solanacearum.

  19. Acupuncture's Cardiovascular Actions: A Mechanistic Perspective.

    Science.gov (United States)

    Longhurst, John

    2013-04-01

    Over the last several decades, there has been an explosion of articles on acupuncture, including studies that have begun to explore mechanisms underlying its analgesic and cardiovascular actions. Modulation of cardiovascular function is most effective during manual and low-frequency, low-intensity electroacupuncture (EA) at a select set of acupoints situated along meridians located over deep somatic nerves on the upper and lower extremities. Stimulation at these acupoints activates underlying sensory neural pathways that project to a number of regions in the central nervous system (CNS) that ultimately regulate autonomic outflow and hence cardiovascular function. A long-loop pathway involving the hypothalamus, midbrain, and medulla underlies EA modulation of reflex increases in blood pressure (BP). Actions of excitatory and inhibitory neurotransmitters in the supraspinal CNS underlie processing of the somatic input and adjustment of autonomic outflow during EA. Acupuncture also decreases elevated blood pressure through actions in the thoracic spinal cord. Reflexes that lower BP likewise are modulated by EA through its actions on sympathetic and parasympathetic nuclei in the medulla. The autonomic influence of acupuncture is slow in onset but prolonged in duration, typically lasting beyond the period of stimulation. Clinical studies suggest that acupuncture can be used to treat cardiac diseases, such as myocardial ischemia and hypertension, associated with overactivity of the sympathetic nervous system.

  20. Myostatin inhibitory region of fish (Paralichthys olivaceus) myostatin-1 propeptide.

    Science.gov (United States)

    Lee, Sang Beum; Kim, Jeong Hwan; Jin, Deuk-Hee; Jin, Hyung-Joo; Kim, Yong Soo

    2016-01-01

    Myostatin (MSTN) is a potent negative regulator of skeletal muscle growth, and its activity is suppressed by MSTN propeptide (MSTNpro), the N-terminal part of MSTN precursor cleaved during post-translational MSTN processing. The current study examined which region of flatfish (Paralichthys olivaceus) MSTN-1 propeptide (MSTN1pro) is critical for MSTN inhibition. Six different truncated forms of MSTN1pro containing N-terminal maltose binding protein (MBP) as a fusion partner were expressed in Escherichia coli, and partially purified by an affinity chromatography for MSTN-inhibitory activity examination. Peptides covering different regions of flatfish MSTN1pro were also synthesized for MSTN-inhibitory activity examination. A MBP-fused MSTN1pro region consisting of residues 45-100 had the same MSTN-inhibitory potency as the full sequence flatfish MSTN1pro (residues 23-265), indicating that the region of flatfish MSTN1pro consisting of residues 45-100 is sufficient to maintain the full MSTN-inhibitory capacity. A MBP-fused MSTN1pro region consisting of residues 45-80 (Pro45-80) also showed MSTN-inhibitory activity with a lower potency, and the Pro45-80 demonstrated its MSTN binding capacity in a pull-down assay, indicating that the MSTN-inhibitory capacity of Pro45-80 is due to its binding to MSTN. Flatfish MSTN1pro synthetic peptides covering residues 45-65, 45-70, and 45-80 demonstrated MSTN-inhibitory activities, but not the synthetic peptide covering residues 45-54, indicating that residues 45-65 of flatfish MSTN1pro are essential for MSTN inhibition. In conclusion, current study show that like the mammalian MSTNpro, the MSTN-inhibitory region of flatfish MSTN1pro resides near its N-terminus, and imply that smaller sizes of MSTNpro can be effectively used in various applications designed for MSTN inhibition. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Angiotensin I-Converting Enzyme (ACE Inhibitory Activity and ACE Inhibitory Peptides of Salmon (Salmo salar Protein Hydrolysates Obtained by Human and Porcine Gastrointestinal Enzymes

    Directory of Open Access Journals (Sweden)

    Małgorzata Darewicz

    2014-08-01

    Full Text Available The objectives of the present study were two-fold: first, to detect whether salmon protein fractions possess angiotensin I-converting enzyme (ACE inhibitory properties and whether salmon proteins can release ACE inhibitory peptides during a sequential in vitro hydrolysis (with commercial porcine enzymes and ex vivo digestion (with human gastrointestinal enzymes. Secondly, to evaluate the ACE inhibitory activity of generated hydrolysates. A two-step ex vivo and in vitro model digestion was performed to simulate the human digestion process. Salmon proteins were degraded more efficiently by porcine enzymes than by human gastrointestinal juices and sarcoplasmic proteins were digested/hydrolyzed more easily than myofibrillar proteins. The ex vivo digested myofibrillar and sarcoplasmic duodenal samples showed IC50 values (concentration required to decrease the ACE activity by 50% of 1.06 and 2.16 mg/mL, respectively. The in vitro hydrolyzed myofibrillar and sarcoplasmic samples showed IC50 values of 0.91 and 1.04 mg/mL, respectively. Based on the results of in silico studies, it was possible to identify 9 peptides of the ex vivo hydrolysates and 7 peptides of the in vitro hydrolysates of salmon proteins of 11 selected peptides. In both types of salmon hydrolysates, ACE-inhibitory peptides IW, IY, TVY and VW were identified. In the in vitro salmon protein hydrolysates an ACE-inhibitory peptides VPW and VY were also detected, while ACE-inhibitory peptides ALPHA, IVY and IWHHT were identified in the hydrolysates generated with ex vivo digestion. In our studies, we documented ACE inhibitory in vitro effects of salmon protein hydrolysates obtained by human and as well as porcine gastrointestinal enzymes.

  2. Nootropic dipeptide noopept enhances inhibitory synaptic transmission in the hippocampus.

    Science.gov (United States)

    Povarov, I S; Kondratenko, R V; Derevyagin, V I; Ostrovskaya, R U; Skrebitskii, V G

    2015-01-01

    Application of nootropic agent Noopept on hippocampal slices from Wistar rats enhanced the inhibitory component of total current induced by stimulation of Shaffer collaterals in CA1 pyramidal neurons, but did not affect the excitatory component. A direct correlation between the increase in the amplitude of inhibitory current and agent concentration was found. The substance did not affect the release of inhibitory transmitters from terminals in the pyramidal neurons, which indicated changes in GABAergic interneurons.

  3. Review: Regulatory mechanisms of gonadotropin-inhibitory hormone (GnIH synthesis and release in photoperiodic animals

    Directory of Open Access Journals (Sweden)

    Kazuyoshi eTsutsui

    2013-04-01

    Full Text Available Gonadotropin-inhibitory hormone (GnIH is a novel hypothalamic neuropeptide that was discovered in quail as an inhibitory factor for gonadotropin release. GnIH inhibits gonadotropin synthesis and release in birds through actions on gonadotropin-releasing hormone (GnRH neurons and gonadotropes, mediated via the GnIH receptor (GnIH-R, GPR147. Subsequently, GnIH was identified in mammals and other vertebrates. As in birds, mammalian GnIH inhibits gonadotropin secretion, indicating a conserved role for this neuropeptide in the control of the hypothalamic-pituitary-gonadal (HPG axis across species. Identification of the regulatory mechanisms governing GnIH expression and release is important in understanding the physiological role of the GnIH system. A nocturnal hormone, melatonin, appears to act directly on GnIH neurons through its receptor to induce expression and release of GnIH in quail, a photoperiodic bird. Recently, a similar, but opposite, action of melatonin on the inhibition of expression of mammalian GnIH was shown in hamsters and sheep, photoperiodic mammals. These results in photoperiodic animals demonstrate that GnIH expression is photoperiodically modulated via a melatonin-dependent process. Recent findings indicate that GnIH may be a mediator of stress-induced reproductive disruption in birds and mammals, pointing to a broad role for this neuropeptide in assessing physiological state and modifying reproductive effort accordingly. This paper summarizes the advances made in our knowledge regarding the regulation of GnIH synthesis and release in photoperiodic birds and mammals. This paper also discusses the neuroendocrine integration of environmental signals, such as photoperiods and stress, and internal signals, such as GnIH, melatonin and glucocorticoids, to control avian and mammalian reproduction.

  4. In vitro inhibitory activity of essential oil vapors against Ascosphaera apis.

    Science.gov (United States)

    Kloucek, Pavel; Smid, Jakub; Flesar, Jaroslav; Havlik, Jaroslav; Titera, Dalibor; Rada, Vojtech; Drabek, Ondrej; Kokoska, Ladislav

    2012-02-01

    This work evaluates the in vitro inhibitory activity of 70 essential oils (EOs) in the vapor phase for the control of Chalkbrood disease caused by Ascosphaera apis Maassen ex Claussen (Olive et Spiltoir). Two wild strains isolated from infected honey bee colonies together with one standard collection strain were tested by the microatmosphere method. From 70 EOs, 39 exhibited an antifungal effect against A. apis standard and wild strains. The greatest antifungal action was observed for EO vapors from Armoracia rusticana, followed by Thymus vulgaris, Cymbopogon flexosus, Origanum vulgare and Allium sativum. An investigation of chemical composition by GC-MS revealed, that the most active EOs contained allyl isothiocyanate, citral, carvacrol and diallyl sulfides as the main constituents. The chemical composition plays a key role, as activities of different EOs from the same botanical species were different according to their composition.

  5. Residential Mobility, Inhibitory Control, and Academic Achievement in Preschool

    Science.gov (United States)

    Schmitt, Sara A.; Finders, Jennifer K.; McClelland, Megan M.

    2015-01-01

    Research Findings: The present study investigated the direct effects of residential mobility on children's inhibitory control and academic achievement during the preschool year. It also explored fall inhibitory control and academic skills as mediators linking residential mobility and spring achievement. Participants included 359 preschool children…

  6. Population activity structure of excitatory and inhibitory neurons.

    Science.gov (United States)

    Bittner, Sean R; Williamson, Ryan C; Snyder, Adam C; Litwin-Kumar, Ashok; Doiron, Brent; Chase, Steven M; Smith, Matthew A; Yu, Byron M

    2017-01-01

    Many studies use population analysis approaches, such as dimensionality reduction, to characterize the activity of large groups of neurons. To date, these methods have treated each neuron equally, without taking into account whether neurons are excitatory or inhibitory. We studied population activity structure as a function of neuron type by applying factor analysis to spontaneous activity from spiking networks with balanced excitation and inhibition. Throughout the study, we characterized population activity structure by measuring its dimensionality and the percentage of overall activity variance that is shared among neurons. First, by sampling only excitatory or only inhibitory neurons, we found that the activity structures of these two populations in balanced networks are measurably different. We also found that the population activity structure is dependent on the ratio of excitatory to inhibitory neurons sampled. Finally we classified neurons from extracellular recordings in the primary visual cortex of anesthetized macaques as putative excitatory or inhibitory using waveform classification, and found similarities with the neuron type-specific population activity structure of a balanced network with excitatory clustering. These results imply that knowledge of neuron type is important, and allows for stronger statistical tests, when interpreting population activity structure.

  7. Population activity structure of excitatory and inhibitory neurons.

    Directory of Open Access Journals (Sweden)

    Sean R Bittner

    Full Text Available Many studies use population analysis approaches, such as dimensionality reduction, to characterize the activity of large groups of neurons. To date, these methods have treated each neuron equally, without taking into account whether neurons are excitatory or inhibitory. We studied population activity structure as a function of neuron type by applying factor analysis to spontaneous activity from spiking networks with balanced excitation and inhibition. Throughout the study, we characterized population activity structure by measuring its dimensionality and the percentage of overall activity variance that is shared among neurons. First, by sampling only excitatory or only inhibitory neurons, we found that the activity structures of these two populations in balanced networks are measurably different. We also found that the population activity structure is dependent on the ratio of excitatory to inhibitory neurons sampled. Finally we classified neurons from extracellular recordings in the primary visual cortex of anesthetized macaques as putative excitatory or inhibitory using waveform classification, and found similarities with the neuron type-specific population activity structure of a balanced network with excitatory clustering. These results imply that knowledge of neuron type is important, and allows for stronger statistical tests, when interpreting population activity structure.

  8. Population activity structure of excitatory and inhibitory neurons

    Science.gov (United States)

    Doiron, Brent

    2017-01-01

    Many studies use population analysis approaches, such as dimensionality reduction, to characterize the activity of large groups of neurons. To date, these methods have treated each neuron equally, without taking into account whether neurons are excitatory or inhibitory. We studied population activity structure as a function of neuron type by applying factor analysis to spontaneous activity from spiking networks with balanced excitation and inhibition. Throughout the study, we characterized population activity structure by measuring its dimensionality and the percentage of overall activity variance that is shared among neurons. First, by sampling only excitatory or only inhibitory neurons, we found that the activity structures of these two populations in balanced networks are measurably different. We also found that the population activity structure is dependent on the ratio of excitatory to inhibitory neurons sampled. Finally we classified neurons from extracellular recordings in the primary visual cortex of anesthetized macaques as putative excitatory or inhibitory using waveform classification, and found similarities with the neuron type-specific population activity structure of a balanced network with excitatory clustering. These results imply that knowledge of neuron type is important, and allows for stronger statistical tests, when interpreting population activity structure. PMID:28817581

  9. Interleukin-4 but not interleukin-10 inhibits the production of leukemia inhibitory factor by rheumatoid synovium and synoviocytes.

    Science.gov (United States)

    Dechanet, J; Taupin, J L; Chomarat, P; Rissoan, M C; Moreau, J F; Banchereau, J; Miossec, P

    1994-12-01

    The expression of the proinflammatory cytokine leukemia inhibitory factor (LIF) has been reported in the cartilage and synovium of rheumatoid arthritis (RA) patients. Here, we show that high levels of LIF were constitutively produced by cultures of synovium pieces. Low levels of LIF were produced spontaneously by isolated synoviocytes, but interleukin (IL)-1 beta caused a fourfold enhancement of this secretion. The anti-inflammatory cytokine IL-4 reduced the production of LIF by synovium pieces by 75%, as observed earlier with IL-6, IL-1 beta and tumor necrosis factor (TNF)-alpha. IL-4 had a direct effect since it inhibited LIF production by unstimulated and IL-1 beta- or TNF-alpha-stimulated synoviocytes. Conversely, IL-4 enhanced the production of IL-6, which shares with LIF biological activities and receptor components. The inhibitory effect of IL-4 was dose dependent and was reversed using a blocking anti-IL-4 receptor antibody. Similar inhibitory action of IL-4 on LIF production was observed on synovium pieces from patients with osteoarthritis and on normal synoviocytes. IL-10, another anti-inflammatory cytokine acting on monocytes, had no effect on LIF production by either synovium pieces or isolated synoviocytes. Thus, the production of LIF by synovium tissue was inhibited by IL-4 through both a direct effect on synoviocytes and an indirect effect by inhibition of the production of LIF-inducing cytokines.

  10. Unsupervised Learning of Action Primitives

    DEFF Research Database (Denmark)

    Baby, Sanmohan; Krüger, Volker; Kragic, Danica

    2010-01-01

    and scale, the use of the object can provide a strong invariant for the detection of motion primitives. In this paper we propose an unsupervised learning approach for action primitives that makes use of the human movements as well as the object state changes. We group actions according to the changes......Action representation is a key issue in imitation learning for humanoids. With the recent finding of mirror neurons there has been a growing interest in expressing actions as a combination meaningful subparts called primitives. Primitives could be thought of as an alphabet for the human actions....... In this paper we observe that human actions and objects can be seen as being intertwined: we can interpret actions from the way the body parts are moving, but as well from how their effect on the involved object. While human movements can look vastly different even under minor changes in location, orientation...

  11. Diuretics with carbonic anhydrase inhibitory action: a patent and literature review (2005 - 2013).

    Science.gov (United States)

    Carta, Fabrizio; Supuran, Claudiu T

    2013-01-01

    The benzothiadiazines and high ceiling diuretics (hydrochlorothiazide, hydroflumethiazide, quinethazone, metolazone, chlorthalidone, indapamide, furosemide and bumetanide) contain primary sulfamoyl moieties acting as zinc-binding groups in the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1). These drugs are widely used clinically and were recently shown to weakly inhibit isoforms CA I and II, but to possess stronger activity against isoforms involved in other important pathologies, for example, obesity, cancer, epilepsy and hypertension. The class of clinically used diuretics, with CA inhibitory properties, is the main topic of the review. A patent literature review covering the period from 2005 to 2013 is presented. This section presents an overview of the patent literature in the sulfonamide diuretic field. Most of the patents deal with the combination of diuretic sulfonamide CA inhibitors with other agents useful in the management of cardiovascular diseases and obesity. Such combinations exert a better therapeutic activity compared to similar diuretics that do not inhibit CAs, raising the question of the polypharmacological and drug repositioning effects of these old drugs. These effects seem to be due to the potent inhibition of such drugs against CA isoforms present in kidneys and blood vessels, which explain both the blood pressure lowering effects as well as organ-protective activity of the drugs. An explanation of these data is provided by the fact that inhibition of the renal CAs leads to a large increase of the nitrite excretion in urine, suggesting that renal CAs are involved in nitrite reabsorption in humans. Important lessons for the drug design of sulfonamide CA inhibitors (CAIs) can be drawn from these data.

  12. Enzyme inhibitory activity of selected Philippine plants

    International Nuclear Information System (INIS)

    Sasotona, Joseph S.; Hernandez, Christine C.

    2015-01-01

    In the Philippines, the number one cause of death are cardiovascular diseases. Diseases linked with inflammation are proliferating. This research aims to identify plant extracts that have potential activity of cholesterol-lowering, anti-hypertension, anti-gout, anti-inflammatory and fat blocker agents. Although there are commercially available drugs to treat the aforementioned illnesses, these medicine have adverse side-effects, aside from the fact that they are expensive. The results of this study will serve as added knowledge to contribute to the development of cheaper, more readily available, and effective alternative medicine. 100 plant extracts from different areas in the Philippines have been tested for potential inhibitory activity against Hydroxymethylglutaryl-coenzyme A (HMG-CoA), Lipoxygenase, and Xanthine Oxidase. The plant samples were labeled with codes and distributed to laboratories for blind testing. The effective concentration of the samples tested for Xanthine oxidase is 100 ppm. Samples number 9, 11, 14, 29, 43, 46, and 50 have shown significant inhibitory activity at 78.7%, 78.4%, 70%, 89.2%, 79%, 67.4%, and 67.5% respectively. Samples tested for Lipoxygenase inhibition were set at 33ppm. Samples number 2, 37, 901, 1202, and 1204 have shown significant inhibitory activity at 66, 84.9%, 88.55%, 93.3%, and 84.7% respectively. For HMG-CoA inhibition, the effective concentration of the samples used was 100 ppm. Samples number 1 and 10 showed significant inhibitory activity at 90.1% and 81.8% respectively. (author)

  13. Time Course of Brain Network Reconfiguration Supporting Inhibitory Control.

    Science.gov (United States)

    Popov, Tzvetan; Westner, Britta U; Silton, Rebecca L; Sass, Sarah M; Spielberg, Jeffrey M; Rockstroh, Brigitte; Heller, Wendy; Miller, Gregory A

    2018-05-02

    Hemodynamic research has recently clarified key nodes and links in brain networks implementing inhibitory control. Although fMRI methods are optimized for identifying the structure of brain networks, the relatively slow temporal course of fMRI limits the ability to characterize network operation. The latter is crucial for developing a mechanistic understanding of how brain networks shift dynamically to support inhibitory control. To address this critical gap, we applied spectrally resolved Granger causality (GC) and random forest machine learning tools to human EEG data in two large samples of adults (test sample n = 96, replication sample n = 237, total N = 333, both sexes) who performed a color-word Stroop task. Time-frequency analysis confirmed that recruitment of inhibitory control accompanied by slower behavioral responses was related to changes in theta and alpha/beta power. GC analyses revealed directionally asymmetric exchanges within frontal and between frontal and parietal brain areas: top-down influence of superior frontal gyrus (SFG) over both dorsal ACC (dACC) and inferior frontal gyrus (IFG), dACC control over middle frontal gyrus (MFG), and frontal-parietal exchanges (IFG, precuneus, MFG). Predictive analytics confirmed a combination of behavioral and brain-derived variables as the best set of predictors of inhibitory control demands, with SFG theta bearing higher classification importance than dACC theta and posterior beta tracking the onset of behavioral response. The present results provide mechanistic insight into the biological implementation of a psychological phenomenon: inhibitory control is implemented by dynamic routing processes during which the target response is upregulated via theta-mediated effective connectivity within key PFC nodes and via beta-mediated motor preparation. SIGNIFICANCE STATEMENT Hemodynamic neuroimaging research has recently clarified regional structures in brain networks supporting inhibitory control. However, due to

  14. Parallel prefrontal pathways reach distinct excitatory and inhibitory systems in memory-related rhinal cortices.

    Science.gov (United States)

    Bunce, Jamie G; Zikopoulos, Basilis; Feinberg, Marcia; Barbas, Helen

    2013-12-15

    To investigate how prefrontal cortices impinge on medial temporal cortices we labeled pathways from the anterior cingulate cortex (ACC) and posterior orbitofrontal cortex (pOFC) in rhesus monkeys to compare their relationship with excitatory and inhibitory systems in rhinal cortices. The ACC pathway terminated mostly in areas 28 and 35 with a high proportion of large terminals, whereas the pOFC pathway terminated mostly through small terminals in area 36 and sparsely in areas 28 and 35. Both pathways terminated in all layers. Simultaneous labeling of pathways and distinct neurochemical classes of inhibitory neurons, followed by analyses of appositions of presynaptic and postsynaptic fluorescent signal, or synapses, showed overall predominant association with spines of putative excitatory neurons, but also significant interactions with presumed inhibitory neurons labeled for calretinin, calbindin, or parvalbumin. In the upper layers of areas 28 and 35 the ACC pathway was associated with dendrites of neurons labeled with calretinin, which are thought to disinhibit neighboring excitatory neurons, suggesting facilitated hippocampal access. In contrast, in area 36 pOFC axons were associated with dendrites of calbindin neurons, which are poised to reduce noise and enhance signal. In the deep layers, both pathways innervated mostly dendrites of parvalbumin neurons, which strongly inhibit neighboring excitatory neurons, suggesting gating of hippocampal output to other cortices. These findings suggest that the ACC, associated with attention and context, and the pOFC, associated with emotional valuation, have distinct contributions to memory in rhinal cortices, in processes that are disrupted in psychiatric diseases. Copyright © 2013 Wiley Periodicals, Inc.

  15. Coagulation factor VII variants resistant to inhibitory antibodies.

    Science.gov (United States)

    Branchini, Alessio; Baroni, Marcello; Pfeiffer, Caroline; Batorova, Angelika; Giansily-Blaizot, Muriel; Schved, Jean F; Mariani, Guglielmo; Bernardi, Francesco; Pinotti, Mirko

    2014-11-01

    Replacement therapy is currently used to prevent and treat bleeding episodes in coagulation factor deficiencies. However, structural differences between the endogenous and therapeutic proteins might increase the risk for immune complications. This study was aimed at identifying factor (F)VII variants resistant to inhibitory antibodies developed after treatment with recombinant activated factor VII (rFVIIa) in a FVII-deficient patient homozygous for the p.A354V-p.P464Hfs mutation, which predicts trace levels of an elongated FVII variant in plasma. We performed fluorescent bead-based binding, ELISA-based competition as well as fluorogenic functional (activated FX and thrombin generation) assays in plasma and with recombinant proteins. We found that antibodies displayed higher affinity for the active than for the zymogen FVII (half-maximal binding at 0.54 ± 0.04 and 0.78 ± 0.07 BU/ml, respectively), and inhibited the coagulation initiation phase with a second-order kinetics. Isotypic analysis showed a polyclonal response with a large predominance of IgG1. We hypothesised that structural differences in the carboxyl-terminus between the inherited FVII and the therapeutic molecules contributed to the immune response. Intriguingly, a naturally-occurring, poorly secreted and 5-residue truncated FVII (FVII-462X) escaped inhibition. Among a series of truncated rFVII molecules, we identified a well-secreted and catalytically competent variant (rFVII-464X) with reduced binding to antibodies (half-maximal binding at 0.198 ± 0.003 BU/ml) as compared to the rFVII-wt (0.032 ± 0.002 BU/ml), which led to a 40-time reduced inhibition in activated FX generation assays. Taken together our results provide a paradigmatic example of mutation-related inhibitory antibodies, strongly support the FVII carboxyl-terminus as their main target and identify inhibitor-resistant FVII variants.

  16. Bacteriocin-like inhibitory activities of seven Lactobacillus delbrueckii subsp. bulgaricus strains against antibiotic susceptible and resistant Helicobacter pylori strains.

    Science.gov (United States)

    Boyanova, L; Gergova, G; Markovska, R; Yordanov, D; Mitov, I

    2017-12-01

    The aim of the study was to detect anti-Helicobacter pylori activity of seven Lactobacillus delbrueckii subsp. bulgaricus (GLB) strains by four cell-free supernatant (CFS) types. Activity of non-neutralized and non-heat-treated (CFSs1), non-neutralized and heat-treated (CFSs2), pH neutralized, catalase-treated and non-heat-treated (CFSs3), or neutralized, catalase- and heat-treated (CFSs4) CFSs against 18 H. pylori strains (11 of which with antibiotic resistance) was evaluated. All GLB strains produced bacteriocin-like inhibitory substances (BLISs), the neutralized CFSs of two GLB strains inhibited >81% of test strains and those of four GLB strains were active against >71% of antibiotic resistant strains. Two H. pylori strains were BLIS resistant. The heating did not reduce the CFS activity. Briefly, all GLB strains evaluated produced heat-stable BLISs, although GLB and H. pylori strain susceptibility patterns exhibited differences. Bacteriocin-like inhibitory substance activity can be an advantage for the probiotic choice for H. pylori infection control. In this study, anti-Helicobacter pylori activity of seven Lactobacillus delbrueckii subsp. bulgaricus (GLB) strains was evaluated by four cell-free supernatant (CFS) types. The GLB strains produced heat-stable bacteriocin-like inhibitory substances (BLISs) with a strong anti-H. pylori activity and some neutralized, catalase- and heat-treated CFSs inhibited >83% of the test strains. Bacteriocin-like inhibitory substance production of GLB strains can render them valuable probiotics in the control of H. pylori infection. © 2017 The Society for Applied Microbiology.

  17. Synergy and mechanism of action of α-mangostin and ceftazidime against ceftazidime-resistant Acinetobacter baumannii.

    Science.gov (United States)

    Pimchan, T; Maensiri, D; Eumkeb, G

    2017-10-01

    To address the resistance of Acinetobacter baumannii to β-lactam antibiotics, combination therapy between different antibiotic classes is increasingly used. The antibacterial activity of α-mangostin (AMT) alone or in combination with ceftazidime (CTZ) was investigated against ceftazidime-resistant A. baumannii DMST 45378 (CRAB). Initial screening showed that A. baumannii strains possessed AmpC β-lactamase (AmpC), extended-spectrum beta-lactamase (ESBL) and metallo-β-lactamases (MBL). Minimum inhibitory concentrations (MICs) of all test agents were >800 μg ml -1 against CRAB. The combination of AMT/CTZ exhibited a fractional inhibitory concentration index (FICI) of Type IV β-lactamase was inhibited by AMT. The data suggest that AMT in combination with CTZ is synergistic and efficient against CRAB. The data also indicate that the AMT/CTZ combination may target multiple structures on the bacterial cell surface. This represents the first report of this effect on CRAB and could potentially be expanded into in vivo studies. Significance and Impact of the Study: Acinetobacter baumannii strains cause serious infections, patient mortality, and have been reported to rise of multidrug resistance. This article represents the first report of using α-mangostin plus ceftazidime against these resistant strains and its mechanism of action. α-mangostin has no cytotoxic effects. Therefore, α-mangostin has strong potential for development as a useful, novel adjunct phytopharmaceutical to ceftazidime synergistically for the treatment of these strains. The synergy approach could potentially be a novel tool to combat the resistant strains. © 2017 The Society for Applied Microbiology.

  18. Influence of temperature on the inhibitory potency of Eucalyptus honey against Candida albicans

    Directory of Open Access Journals (Sweden)

    Ahmed Moussa

    2012-12-01

    Full Text Available Objective: To evaluate the effects of heat processing on the antifungal activity of honey. Methods: A sample of the honey of eucalyptus was divided into four portions of 250 g each. One of the four portions obtained from studied honey was not heated (not heated fraction 25曟, the other portions were placed in water bath during 24 hours at 40 曟, 60 曟 and 80曟 temperatures. The HMF rates, Acidity, pH and the index of refraction were determined by harmonized methods. The antifungal tests (Minimum Inhibitory Concentration were carried out on Sabouraud agar medium embedded with honey according to dilution test. Results: The moisture shows values of 15.65% and 15.83%, pH between 4.10 and 4.24, the free acidity ranges between 33.8 and 38.36 meq kg-1, hydroxymethylfurfural (HMF content shows values between 28.8 and 103.44 mg kg-1. The antifungal action of the non-heated fraction (Fc of honey in vitro was marked 40 % (vol/vol than heated fractions of honey (42%, 44%, and 45% vol/vol. respectively The antifungal activity of each fraction decreased in the following order: Fct曘 25 > Fct曘 40 > Fct曘 60 > Fct曘 80]. Conclusion: our findings indicate that different levels of parameters physical-chemical properties of honey to different temperatures showed inhibitory activity against C. albicans with variable degrees.

  19. The role of right prefrontal and medial cortex in response inhibition: interfering with action restraint and action cancellation using transcranial magnetic brain stimulation.

    Science.gov (United States)

    Dambacher, Franziska; Sack, Alexander T; Lobbestael, Jill; Arntz, Arnoud; Brugmann, Suzanne; Schuhmann, Teresa

    2014-08-01

    The ability of inhibiting impulsive urges is paramount for human behavior. Such successful response inhibition has consistently been associated with activity in pFC. The current study aims to unravel the differential involvement of different areas within right pFC for successful action restraint versus action cancellation. These two conceptually different aspects of action inhibition were measured with a go/no-go task (action restraint) and a stop signal task (action cancellation). Localization of relevant prefrontal activation was based on fMRI data. Significant task-related activation during successful action restraint was localized for each participant individually in right anterior insula (rAI), right superior frontal gyrus, and pre-SMA. Activation during successful action cancellation was localized in rAI, right middle frontal gyrus, and pre-SMA. Subsequently, fMRI-guided continuous thetaburst stimulation was applied to these regions. Results showed that the disruption of neural activity in rAI reduced both the ability to restrain (go/no-go) and cancel (stop signal) responses. In contrast, continuous thetaburst stimulation-induced disruption of the right superior frontal gyrus specifically impaired the ability to restrain from responding (go/no-go), while leaving the ability for action cancellation largely intact. Stimulation applied to right middle frontal gyrus and pre-SMA did not affect inhibitory processing in neither of the two tasks. These findings provide a more comprehensive perspective on the role of pFC in inhibition and cognitive control. The results emphasize the role of inferior frontal regions for global inhibition, whereas superior frontal regions seem to be specifically relevant for successful action restraint.

  20. Egg-yolk protein by-product as a source of ACE-inhibitory peptides obtained with using unconventional proteinase from Asian pumpkin (Cucurbita ficifolia).

    Science.gov (United States)

    Eckert, Ewelina; Zambrowicz, Aleksandra; Pokora, Marta; Setner, Bartosz; Dąbrowska, Anna; Szołtysik, Marek; Szewczuk, Zbigniew; Polanowski, Antoni; Trziszka, Tadeusz; Chrzanowska, Józefa

    2014-10-14

    In the present study angiotensin I-converting enzyme (ACE) inhibitory peptides were isolated from egg-yolk protein preparation (YP). Enzymatic hydrolysis conducted using unconventional enzyme from Cucurbita ficifolia (dose: 1000 U/mg of hydrolyzed YP (E/S (w/w)=1:7.52)) was employed to obtain protein hydrolysates. The 4-h hydrolysate exhibited a significant (IC₅₀=482.5 μg/mL) ACE inhibitory activity. Moreover, hydrolysate showed no cytotoxic activity on human and animal cell lines which makes it a very useful multifunctional method for peptide preparation. The compiled isolation procedure (ultrafiltration, size-exclusion chromatography and RP-HPLC) of bioactive peptides from YP hydrolysate resulted in obtaining peptides with the strong ACE inhibitory activity. One homogeneous and three heterogeneous peptide fractions were identified. The peptides were composed of 9-18 amino-acid residues, including mainly arginine and leucine at the N-terminal positions. To confirm the selected bioactive peptide sequences their analogs were chemically synthesized and tested. Peptide LAPSLPGKPKPD showed the strongest ACE inhibitory activity, with IC₅₀ value of 1.97 μmol/L. Peptides with specific biological activity can be used in pharmaceutical, cosmetic or food industries. Because of their potential role as physiological modulators, as well as theirhigh safety profile, they can be used as natural pharmacological compounds or functional food ingredients. The development of biotechnological solutions to obtain peptides with desired biological activity is already in progress. Studies in this area are focused on using unconventional highly specific enzymes and more efficient methods developed to conduct food process technologies. Natural peptides have many advantages. They are mainly toxicologically safe, have wide spectra of therapeutic actions, exhibit less side effects compared to synthetic drugs and are more efficiently absorbed in the intestinal tract. The complexity of

  1. Inhibitory effect of rose hip (Rosa canina L.) on melanogenesis in mouse melanoma cells and on pigmentation in brown guinea pigs.

    Science.gov (United States)

    Fujii, Takashi; Ikeda, Katsumi; Saito, Morio

    2011-01-01

    The compounds present in rose hips exerting an inhibitory action against melanogenesis in B16 mouse melanoma cells were investigated by dividing an aqueous extract of rose hips (RE) into four fractions. The 50% ethanol eluate from a DIAION HP-20 column significantly reduced the production of melanin and was mainly composed of procyanidin glycosides. We also found that this 50% ethanol eluate reduced the intracellular tyrosinase activity and also had a direct inhibitory effect on tyrosinase obtained as a protein mixture from the melanoma cell lysate. We also investigated the effect of orally administering RE on skin pigmentation in brown guinea pigs, and found that the pigmentation was inhibited together with the tyrosinase activity in the skin. These data collectively suggest that proanthocyanidins from RE inhibited melanogenesis in mouse melanoma cells and guinea pig skin, and could be useful as a skin-whitening agent when taken orally.

  2. Growth-Inhibitory and Antiangiogenic Activity of the MEK Inhibitor PD0325901 in Malignant Melanoma with or without BRAF Mutations

    Directory of Open Access Journals (Sweden)

    Ludovica Ciuffreda

    2009-08-01

    Full Text Available The Raf/MEK/ERK pathway is an importantmediator of tumor cell proliferation and angiogenesis. Here, weinvestigated the growth-inhibitory and antiangiogenic properties of PD0325901, a novel MEK inhibitor, in human melanoma cells. PD0325901 effects were determined in a panel of melanoma cell lines with different genetic aberrations. PD0325901 markedly inhibited ERK phosphorylation and growth of both BRAF mutant and wild-type melanoma cell lines, with IC50 in the nanomolar range even in the least responsive models. Growth inhibition was observed both in vitro and in vivo in xenograft models, regardless of BRAF mutation status, and was due to G1-phase cell cycle arrest and subsequent induction of apoptosis. Cell cycle (cyclin D1, c-Myc, and p27KIP1 and apoptosis (Bcl-2 and survivin regulators were modulated by PD0325901 at the protein level. Gene expression profiling revealed profound modulation of several genes involved in the negative control of MAPK signaling and melanoma cell differentiation, suggesting alternative, potentially relevant mechanisms of action. Finally, PD0325901 inhibited the production of the proangiogenic factors vascular endothelial growth factor and interleukin 8 at a transcriptional level. In conclusion, PD0325901 exerts potent growth-inhibitory, proapoptotic, and antiangiogenic activity in melanoma lines, regardless of their BRAF mutation status. Deeper understanding of the molecular mechanisms of action of MEK inhibitors will likely translate into more effective treatment strategies for patients experiencing malignant melanoma.

  3. Comparative phytochemical and growth inhibitory studies on the leaf ...

    African Journals Online (AJOL)

    Comparative phytochemical and growth inhibitory studies on the leaf and root bark extracts of securinega Virosa (roxb ex. Willd) baill ... The growth inhibitory tests were carried out between 1-30 mg/ in a period of 24-96 h while the phytochemical screening was carried out on the plant parts using standard methods. At 24 h ...

  4. Inhibitory control in childhood stuttering

    NARCIS (Netherlands)

    Eggers, K.; de Nil, L.; Van den Bergh, B.R.H.

    2013-01-01

    Purpose The purpose of this study was to investigate whether previously reported parental questionnaire-based differences in inhibitory control (IC; Eggers, De Nil, & Van den Bergh, 2010) would be supported by direct measurement of IC using a computer task. Method Participants were 30 children who

  5. Optimization of inhibitory decision rules relative to length and coverage

    KAUST Repository

    Alsolami, Fawaz; Chikalov, Igor; Moshkov, Mikhail; Zielosko, Beata

    2012-01-01

    The paper is devoted to the study of algorithms for optimization of inhibitory rules relative to the length and coverage. In contrast with usual rules that have on the right-hand side a relation "attribute ≠ value", inhibitory rules have a relation

  6. INHIBITORY EFFECT OF SALVIA SCLAREA

    African Journals Online (AJOL)

    rakoe

    2011-11-02

    Nov 2, 2011 ... This study demonstrated anti-herpes simplex virus (HSV) activity of lavender, sage and ... Green monkey kidney cells were protected from HSV-2 infection by ... The highest inhibitory effect against HSV-2 was observed after treatment ..... some nuclear-replicating eukaryotic DNA viruses with large genomes.

  7. COMPARATIVE EVALUATION OF INHIBITORY ACTIVITY OF ...

    African Journals Online (AJOL)

    Osondu

    2013-02-26

    Feb 26, 2013 ... especially the four bacteria isolates used in this study are present in the epiphgram of both normal and ... Keyword: Albino snail, Archachatina marginata, Inhibitory activity, Epiphgram, Bacteria isolate. Introduction .... evolution.

  8. Inhibitory Effect of Gamma-Irradiated Chitosan on the Growth of Denitrifiers

    Directory of Open Access Journals (Sweden)

    Javier Vilcáez

    2009-01-01

    Full Text Available In order to find an environmentally benign substitute to hazardous inhibitory agents, the inhibitory effect of -irradiated chitosans against a mixed culture of denitrifying bacteria was experimentally evaluated. Unlike other studies using pure aerobic cultures, the observed effect was not a complete inhibition but a transient inhibition reflected by prolonged lag phases and reduced growth rates. Raw chitosan under acid conditions (pH 6.3 exerted the strongest inhibition followed by the 100 kGy and 500 kGy irradiated chitosans, respectively. Therefore, because the molecular weight of chitosan decreases with the degree of -irradiation, the inhibitory properties of chitosan due to its high molecular weight were more relevant than the inhibitory properties gained due to the modification of the surface charge and/or chemical structure by -irradiation. High dosage of -irradiated appeared to increase the growth of mixed denitrifying bacteria in acid pH media. However, in neutral pH media, high dosage of -irradiation appeared to enhance the inhibitory effect of chitosan.

  9. Inhibitory Effect of Corn Silk on Skin Pigmentation

    OpenAIRE

    Sang Yoon Choi; Yeonmi Lee; Sung Soo Kim; Hyun Min Ju; Ji Hwoon Baek; Chul-Soo Park; Dong-Hyuk Lee

    2014-01-01

    In this study, the inhibitory effect of corn silk on melanin production was evaluated. This study was performed to investigate the inhibitory effect of corn silk on melanin production in Melan-A cells by measuring melanin production and protein expression. The corn silk extract applied on Melan-A cells at a concentration of 100 ppm decreased melanin production by 37.2% without cytotoxicity. This was a better result than arbutin, a positive whitening agent, which exhibited a 26.8% melanin prod...

  10. Inhibitory Control Mediates the Association between Perceived Stress and Secure Relationship Quality

    Directory of Open Access Journals (Sweden)

    Toria Herd

    2018-02-01

    Full Text Available Past research has demonstrated negative associations between exposure to stressors and quality of interpersonal relationships among children and adolescents. Nevertheless, underlying mechanisms of this association remain unclear. Chronic stress has been shown to disrupt prefrontal functioning in the brain, including inhibitory control abilities, and evidence is accumulating that inhibitory control may play an important role in secure interpersonal relationship quality, including peer problems and social competence. In this prospective longitudinal study, we examine whether changes in inhibitory control, measured at both behavioral and neural levels, mediate the association between stress and changes in secure relationship quality with parents and peers. The sample included 167 adolescents (53% males who were first recruited at age 13 or 14 years and assessed annually three times. Adolescents’ inhibitory control was measured by their behavioral performance and brain activities, and adolescents self-reported perceived stress levels and relationship quality with mothers, fathers, and peers. Results suggest that behavioral inhibitory control mediates the association between perceived stress and adolescent’s secure relationship quality with their mothers and fathers, but not their peers. In contrast, given that stress was not significantly correlated with neural inhibitory control, we did not further test the mediation path. Our results highlight the role of inhibitory control as a process through which stressful life experiences are related to impaired secure relationship quality between adolescents and their mothers and fathers.

  11. Inhibitory Control Mediates the Association between Perceived Stress and Secure Relationship Quality.

    Science.gov (United States)

    Herd, Toria; Li, Mengjiao; Maciejewski, Dominique; Lee, Jacob; Deater-Deckard, Kirby; King-Casas, Brooks; Kim-Spoon, Jungmeen

    2018-01-01

    Past research has demonstrated negative associations between exposure to stressors and quality of interpersonal relationships among children and adolescents. Nevertheless, underlying mechanisms of this association remain unclear. Chronic stress has been shown to disrupt prefrontal functioning in the brain, including inhibitory control abilities, and evidence is accumulating that inhibitory control may play an important role in secure interpersonal relationship quality, including peer problems and social competence. In this prospective longitudinal study, we examine whether changes in inhibitory control, measured at both behavioral and neural levels, mediate the association between stress and changes in secure relationship quality with parents and peers. The sample included 167 adolescents (53% males) who were first recruited at age 13 or 14 years and assessed annually three times. Adolescents' inhibitory control was measured by their behavioral performance and brain activities, and adolescents self-reported perceived stress levels and relationship quality with mothers, fathers, and peers. Results suggest that behavioral inhibitory control mediates the association between perceived stress and adolescent's secure relationship quality with their mothers and fathers, but not their peers. In contrast, given that stress was not significantly correlated with neural inhibitory control, we did not further test the mediation path. Our results highlight the role of inhibitory control as a process through which stressful life experiences are related to impaired secure relationship quality between adolescents and their mothers and fathers.

  12. Identification of dipeptidyl peptidase-IV inhibitory peptides from mare whey protein hydrolysates.

    Science.gov (United States)

    Song, J J; Wang, Q; Du, M; Ji, X M; Mao, X Y

    2017-09-01

    Inhibition of dipeptidyl peptidase-IV (DPP-IV) activity is a promising strategy for treatment of type 2 diabetes. In the current study, DPP-IV inhibitory peptides were identified from mare whey protein hydrolysates obtained by papain. The results showed that all the mare whey protein hydrolysates obtained at various hydrolysis durations possessed more potent DPP-IV inhibitory activity compared with intact whey protein. The 4-h hydrolysates showed the greatest DPP-IV inhibitory activity with half-maximal inhibitory concentration of 0.18 mg/mL. The 2 novel peptides from 4-h hydrolysate fractions separated by successive chromatographic steps were characterized by liquid chromatography-electrospray ionization tandem mass spectrometry. The novel peptides Asn-Leu-Glu-Ile-Ile-Leu-Arg and Thr-Gln-Met-Val-Asp-Glu-Glu-Ile-Met-Glu-Lys-Phe-Arg, which corresponded to β-lactoglobulin 1 f(71-77) and β-lactoglobulin 1 f(143-155), demonstrated DPP-IV inhibitory activity with half-maximal inhibitory concentrations of 86.34 and 69.84 μM, respectively. The DPP-IV inhibitory activity of the 2 peptides was retained or even improved after simulated gastrointestinal digestion in vitro. Our findings indicate that mare whey protein-derived peptides may possess potential as functional food ingredients in the management of type 2 diabetes. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  13. Attention, biological motion, and action recognition.

    Science.gov (United States)

    Thompson, James; Parasuraman, Raja

    2012-01-02

    Interacting with others in the environment requires that we perceive and recognize their movements and actions. Neuroimaging and neuropsychological studies have indicated that a number of brain regions, particularly the superior temporal sulcus, are involved in a number of processes essential for action recognition, including the processing of biological motion and processing the intentions of actions. We review the behavioral and neuroimaging evidence suggesting that while some aspects of action recognition might be rapid and effective, they are not necessarily automatic. Attention is particularly important when visual information about actions is degraded or ambiguous, or if competing information is present. We present evidence indicating that neural responses associated with the processing of biological motion are strongly modulated by attention. In addition, behavioral and neuroimaging evidence shows that drawing inferences from the actions of others is attentionally demanding. The role of attention in action observation has implications for everyday social interactions and workplace applications that depend on observing, understanding and interpreting actions. Published by Elsevier Inc.

  14. Histamine release inhibitory activity of Piper nigrum leaf.

    Science.gov (United States)

    Hirata, Noriko; Naruto, Shunsuke; Inaba, Kazunori; Itoh, Kimihisa; Tokunaga, Masashi; Iinuma, Munekazu; Matsuda, Hideaki

    2008-10-01

    Oral administration of a methanolic extract of Piper nigrum leaf (PN-ext, 50, 200 and 500 mg/kg) showed a potent dose-dependent inhibition of dinitrofluorobenzene (DNFB)-induced cutaneous reaction at 1 h [immediate phase response (IPR)] after and 24 h [late phase response (LPR)] after DNFB challenge in mice which were passively sensitized with anti-dinitrophenyl (DNP) IgE antibody. Ear swelling inhibitory effect of PN-ext (50, 200 and 500 mg/kg, per os (p.o.)) on very late phase response (vLPR) in the model mice was significant but weaker than that on IPR. Oral administration of PN-ext (50, 200 and 500 mg/kg for 7 d) inhibited picryl chloride (PC)-induced ear swelling in PC sensitized mice. PN-ext exhibited in vitro inhibitory effect on compound 48/80-induced histamine release from rat peritoneal mast cells. Two lignans of PN-ext, (-)-cubebin (1) and (-)-3,4-dimethoxy-3,4-desmethylenedioxycubebin (2), were identified as major active principles having histamine release inhibitory activity.

  15. Basic Mechanisms of Action of the Antiepileptic Drugs

    Directory of Open Access Journals (Sweden)

    Kuzmanova R.

    2017-10-01

    Full Text Available Available antiepileptic drugs interact with a variety of different molecular targets. The mechanism of action of most anticonvulsants is most often complex with a number of affected regions. The combination of mechanisms of action of drugs in particular proportions can possibly determine the showcase of its antiepileptic activity. The common factor between the different supposed mechanisms for a number of drugs includes the possibility for modulating the excitatory and inhibitory neurotransmission through effects upon the voltage-gated ion channels, synaptic plasticity, heterogeneous receptors, and metabolism of neurotransmitters. There are controversial data on the extent to which a specific action can be the reason for the wholesome anticonvulsive characteristics of various medications, as well as the relation with the presence of undesired drug effects. The complexity of the action of some antiepileptic drugs creates conditions for optimal choice during therapy. In many cases, the insufficient familiarity with individual genetic differences and the disease related receptor damages can hinder defining a particular drug action. Characterizing the mechanisms of action of the present antiepileptic medications would increase the understanding for the pathophysiological mechanisms of epileptic seizures, as well as the development of new therapeutic strategies. The development of novel antiepileptic drugs and the ongoing research regarding the mechanism of action of established antiepileptic drugs, are continuously increasing the level of complexity in the spectrum of molecular targets relevant for epilepsy therapy. The current state of knowledge as well as the limitations in our understanding should guide future research aiming for a more detailed elucidation of the impact of genetics and pathophysiological mechanisms on interindividual differences in expression and function of antiepileptic drug targets.

  16. Affirmative Action and Stereotype Threat

    OpenAIRE

    Cohen, Alma

    2015-01-01

    This paper provides experimental evidence on the effect of affirmative action (AA). In particular, we investigate whether affirmative action has a ”stereotype threat effect” – that is, whether AA cues a negative stereotype that leads individuals to conform to the stereotype and adversely affects their performance. Stereotype threat has been shown in the literature to be potentially significant for individuals who identify strongly with the domain of the stereotype and who engage in complex st...

  17. Antibacterial Activity and Action Mechanism of the Essential Oil from Enteromorpha linza L. against Foodborne Pathogenic Bacteria

    Directory of Open Access Journals (Sweden)

    Jayanta Kumar Patra

    2016-03-01

    Full Text Available Foodborne illness and disease caused by foodborne pathogenic bacteria is continuing to increase day by day and it has become an important topic of concern among various food industries. Many types of synthetic antibacterial agents have been used in food processing and food preservation; however, they are not safe and have resulted in various health-related issues. Therefore, in the present study, essential oil from an edible seaweed, Enteromorpha linza (AEO, was evaluated for its antibacterial activity against foodborne pathogens, along with the mechanism of its antibacterial action. AEO at 25 mg/disc was highly active against Bacillus cereus (12.3–12.7 mm inhibition zone and Staphylococcus aureus (12.7–13.3 mm inhibition zone. The minimum inhibitory concentration and minimum bactericidal concentration values of AEO ranged from 12.5–25 mg/mL. Further investigation of the mechanism of action of AEO revealed its strong impairing effect on the viability of bacterial cells and membrane permeability, as indicated by a significant increase in leakage of 260 nm absorbing materials and K+ ions from the cell membrane and loss of high salt tolerance. Taken together, these data suggest that AEO has the potential for use as an effective antibacterial agent that functions by impairing cell membrane permeability via morphological alternations, resulting in cellular lysis and cell death.

  18. Cholinesterase inhibitory activity and structure elucidation of a new phytol derivative and a new cinnamic acid ester from Pycnanthus angolensis

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    Taiwo O. Elufioye

    Full Text Available ABSTRACT The leaves of Pycnanthus angolensis (Welw. Warb., Myristicaceae, are used as memory enhancer and anti-ageing in Nigerian ethnomedicine. This study aimed at evaluating the cholinesterase inhibitory property as well as isolates the bioactive compounds from the plant. The acetylcholinesterase and butyrylcholinesterase inhibitory potentials of extracts, fractions, and isolated compounds were evaluated by colorimetric and TLC bioautographic assay techniques. The extract inhibited both enzymes with activity increasing with purification, ethyl acetate fraction being most active fraction at 65.66 ± 1.06% and 49.38 ± 1.66% against acetylcholinesterase and butyrylcholinesterase, respectively while the supernatant had 77.44 ± 1.18 inhibition against acetylcholinesterase. Two new bioactive compounds, (2E, 18E-3,7,11,15,18-pentamethylhenicosa-2,18-dien-1-ol (named eluptol and [12-(4-hydroxy-3-methyl-oxo-cyclopenta-1,3-dien-1yl-11-methyl-dodecyl](E-3-(3,4-dimethylphenylprop-2-enoate (named omifoate A were isolated from the plant with IC50 of 22.26 µg/ml (AChE, 34.61 µg/ml (BuChE and 6.51 µg/ml (AChE, 9.07 µg/ml (BuChE respectively. The results showed that the plant has cholinesterase inhibitory activity which might be responsible for its memory enhancing action, thus justifying its inclusion in traditional memory enhancing preparations

  19. Sub-inhibitory cefsulodin sensitization of E. coli to β-lactams is mediated by PBP1b inhibition.

    Directory of Open Access Journals (Sweden)

    Sujoy K Sarkar

    Full Text Available The combination of antibiotics is one of the strategies to combat drug-resistant bacteria, though only a handful of such combinations are in use, such as the β-lactam combinations. In the present study, the efficacy of a specific sub-inhibitory concentration of cefsulodin with other β-lactams was evaluated against a range of Gram-negative clinical isolates. This approach increased the sensitivity of the isolates, regardless of the β-lactamase production. The preferred target and mechanism of action of cefsulodin were identified in laboratory strains of Escherichia coli, by examining the effects of deleting the penicillin-binding protein (PBP 1a and 1b encoding genes individually. Deletion of PBP1b was involved in sensitizing the bacteria to β-lactam agents, irrespective of its O-antigen status. Moreover, the use of a sub-inhibitory concentration of cefsulodin in combination with a β-lactam exerted an effect similar to that one obtained for PBP1b gene deletion. We conclude that the identified β-lactam/cefsulodin combination works by inhibiting PBP1b (at least partially despite the involvement of β-lactamases, and therefore could be extended to a broad range of Gram-negative pathogens.

  20. Functional differentiation of macaque visual temporal cortical neurons using a parametric action space.

    Science.gov (United States)

    Vangeneugden, Joris; Pollick, Frank; Vogels, Rufin

    2009-03-01

    Neurons in the rostral superior temporal sulcus (STS) are responsive to displays of body movements. We employed a parametric action space to determine how similarities among actions are represented by visual temporal neurons and how form and motion information contributes to their responses. The stimulus space consisted of a stick-plus-point-light figure performing arm actions and their blends. Multidimensional scaling showed that the responses of temporal neurons represented the ordinal similarity between these actions. Further tests distinguished neurons responding equally strongly to static presentations and to actions ("snapshot" neurons), from those responding much less strongly to static presentations, but responding well when motion was present ("motion" neurons). The "motion" neurons were predominantly found in the upper bank/fundus of the STS, and "snapshot" neurons in the lower bank of the STS and inferior temporal convexity. Most "motion" neurons showed strong response modulation during the course of an action, thus responding to action kinematics. "Motion" neurons displayed a greater average selectivity for these simple arm actions than did "snapshot" neurons. We suggest that the "motion" neurons code for visual kinematics, whereas the "snapshot" neurons code for form/posture, and that both can contribute to action recognition, in agreement with computation models of action recognition.

  1. Performa Inhibitory Control dengan Induksi Sing-a-Song Stress Test pada Dewasa Awal

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    Akhmad Kurniawan

    2018-04-01

    Full Text Available Inhibitory control is able to control attention by inhibiting internal tendencies and external influences. Inhibitory control is controlled by dorsolateral prefrontal cortex and anterior cingulate cortex, that can be affected by stress variable. Sing-a-Song Stress Test (SSST is a current method to induce stress that has never been practiced in study of inhibitory control. This study aimed to determine the effect of SSST against inhibitory control in early adult. Between subjects design was applied in this study. A number of 35 participants with age range from 17 to 21 years old were randomly assigned into experimental group (n = 17 and control group (n = 18. Inhibitory control was measured using Computerized Stroop Color-Word Test (CSCWT. Positive Affect and Negative Affect Schedule (PANAS was used to conduct a manipulation check. Independent-Samples T Test explained no significant effect of stress on inhibitory control (t = -0,117; p > 0,05.

  2. ACTION OF SYNTHETIC DETERGENTS ON THE METABOLISM OF BACTERIA.

    Science.gov (United States)

    Baker, Z; Harrison, R W; Miller, B F

    1941-01-31

    A study of the effects of synthetic detergents and wetting agents on respiration and glycolysis of Gram-positive and Gram-negative microorganisms has led to the following conclusions. 1. All the cationic detergents studied are very effective inhibitors of bacterial metabolism at 1:3000 concentration, and several are equally active at 1:30,000. Few of the anionic detergents inhibit as effectively as the cationic compounds. 2. Gram-positive and Gram-negative microorganisms are equally sensitive to the action of the cationic detergents. On the other hand, all the anionic detergents included in our studies selectively inhibit the metabolism of Gram-positive microorganisms. 3. The inhibitory action of both types of detergents is influenced markedly by hydrogen ion concentration. Cationic detergents exhibit their maximum activity in the alkaline pH range, and the anionic, in the acid range. 4. Studies of homologous series of straight chain alkyl sulfates and sulfoacetates (C(8) to C(18)) demonstrate that maximum inhibition is exerted by the 12, 14, and 16 carbon compounds (lauryl, myristyl, and cetyl). 5. It has been observed that three lauryl esters of amino acids are powerful inhibitors of bacterial metabolism. To our knowledge, the effects on bacterial metabolism of such cationic detergents (without the quaternary ammonium structure) have not been studied previously. Our results demonstrate that other cationic detergents can exhibit an inhibitory activity comparable to quaternary ammonium compounds. 6. Certain detergents stimulate bacterial metabolism at concentrations lower than the inhibiting values. This effect has been found more frequently among the anionic detergents.

  3. Genome-wide fitness test and mechanism-of-action studies of inhibitory compounds in Candida albicans.

    Directory of Open Access Journals (Sweden)

    Deming Xu

    2007-06-01

    Full Text Available Candida albicans is a prevalent fungal pathogen amongst the immunocompromised population, causing both superficial and life-threatening infections. Since C. albicans is diploid, classical transmission genetics can not be performed to study specific aspects of its biology and pathogenesis. Here, we exploit the diploid status of C. albicans by constructing a library of 2,868 heterozygous deletion mutants and screening this collection using 35 known or novel compounds to survey chemically induced haploinsufficiency in the pathogen. In this reverse genetic assay termed the fitness test, genes related to the mechanism of action of the probe compounds are clearly identified, supporting their functional roles and genetic interactions. In this report, chemical-genetic relationships are provided for multiple FDA-approved antifungal drugs (fluconazole, voriconazole, caspofungin, 5-fluorocytosine, and amphotericin B as well as additional compounds targeting ergosterol, fatty acid and sphingolipid biosynthesis, microtubules, actin, secretion, rRNA processing, translation, glycosylation, and protein folding mechanisms. We also demonstrate how chemically induced haploinsufficiency profiles can be used to identify the mechanism of action of novel antifungal agents, thereby illustrating the potential utility of this approach to antifungal drug discovery.

  4. On minimal inhibitory rules for almost all k-valued information systems

    KAUST Repository

    Moshkov, Mikhail; Skowron, Andrzej; Suraj, Zbigniew

    2009-01-01

    The minimal inhibitory rules for information systems can be used for construction of classifiers. We show that almost all information systems from a certain large class of information systems have relatively short minimal inhibitory rules. However

  5. Minimum inhibitory concentrations of medicinal plants used in Northern Peru as antibacterial remedies.

    Science.gov (United States)

    Bussmann, R W; Malca-García, G; Glenn, A; Sharon, D; Chait, G; Díaz, D; Pourmand, K; Jonat, B; Somogy, S; Guardado, G; Aguirre, C; Chan, R; Meyer, K; Kuhlman, A; Townesmith, A; Effio-Carbajal, J; Frías-Fernandez, F; Benito, M

    2010-10-28

    The plant species reported here are traditionally used in Northern Peru to treat bacterial infections, often addressed by the local healers as "inflammation". The aim of this study was to evaluate the minimum inhibitory concentration (MIC) of their antibacterial properties against gram-positive and gram-negative bacteria. The antimicrobial activity of ethanolic and water extracts of 141 plant species was determined using a deep-well broth microdilution method on commercially available bacterial strains. The ethanolic extracts of 51 species inhibited Escherichia coli, and 114 ethanolic extracts inhibited Staphylococcus aureus. In contrast, only 30 aqueous extracts showed activity against Escherichia coli and 38 extracts against Staphylococcus aureus. The MIC concentrations were mostly very high and ranged from 0.008 to 256 mg/ml, with only 36 species showing inhibitory concentrations of extracts exhibited stronger activity and a much broader spectrum of action than the aqueous extracts. Hypericum laricifolium, Hura crepitans, Caesalpinia paipai, Cassia fistula, Hyptis sidifolia, Salvia sp., Banisteriopsis caapi, Miconia salicifolia and Polygonum hydropiperoides showed the lowest MIC values and would be interesting candidates for future research. The presence of antibacterial activity could be confirmed in most species used in traditional medicine in Peru which were assayed in this study. However, the MIC for the species employed showed a very large range, and were mostly very high. Nevertheless, traditional knowledge might provide some leads to elucidate potential candidates for future development of new antibiotic agents. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  6. Cardiac effects of r-79595 and its isomers (r-80122 and r-80123) in an acute heart-failure model - a new class of cardiotonic agents with highly selective phosphodiesterase-iii inhibitory properties

    NARCIS (Netherlands)

    SCHNEIDER, J; BECK, E; HEERS, C; CONRAD, C; DECOURCELLES, DD; WILFFERT, B; Peters, Thies

    1992-01-01

    R 79595 (N-cyclohexyl-N-methyl-2-[[[phenyl (1,2,3,5-tetrahydro-2 oxoimidazo [2,1-b]-quinazolin-7-yl) methylene] amin] oxy] acetamide) and its isomers represent a novel class of compounds with phosphodiesterase (PDE) inhibitory and cardiotonic (positive inotropic) actions. The cardiac effects of this

  7. An investigation into the inhibitory effect of ultraviolet radiation on Trichophyton rubrum.

    Science.gov (United States)

    Cronin, Leah J; Mildren, Richard P; Moffitt, Michelle; Lauto, Antonio; Morton, C Oliver; Stack, Colin M

    2014-01-01

    Fungal infection of nails, onychomycosis, is predominantly caused by Trichophyton rubrum. This infection is an important public health concern due to its persistent nature and high recurrence rates. Alternative treatments are urgently required. One such alternative is phototherapy involving the action of photothermal or photochemical processes. The aim of this novel study was to assess which wavelengths within the ultraviolet (UV) spectrum were inhibitory and equally important nail transmissible. Initial irradiations of T. rubrum spore suspensions were carried out using a tunable wavelength lamp system (fluence ≤3.1 J/cm(2)) at wavelengths between 280 and 400 nm (UVC to UVA) to evaluate which wavelengths prevented fungal growth. Light-emitting diodes (LEDs) of defined wavelengths were subsequently chosen with a view to evaluate and potentially implement this technology as a low-cost "in-home" treatment. Our experiments demonstrated that exposure at 280 nm using an LED with a fluence as low as 0.5 J/cm(2) was inhibitory, i.e., no growth following a 2-week incubation (p < 0.05; one-way ANOVA), while exposure to longer wavelengths was not. A key requirement for the use of phototherapy in the treatment of onychomycosis is that it must be nail transmissible. Our results indicate that the treatment with UVC is not feasible given that there is no overlap between the antifungal activity observed at 280 nm and transmission through the nail plate. However, a potential indirect application of this technology could be the decontamination of reservoirs of infection such as the shoes of infected individuals, thus preventing reinfection.

  8. Disruption of Trophic Inhibitory Signaling in Autism Sepctrum Disorders

    Science.gov (United States)

    2016-12-01

    1 AWARD NUMBER: W81XWH-14-1-0433 TITLE: Disruption of Trophic Inhibitory Signaling in Autism Sepctrum Disorders PRINCIPAL INVESTIGATOR: Anis...SUBTITLE 5a. CONTRACT NUMBER Disruption of Trophic Inhibitory Signaling in Autism Sepctrum Disorders 5b. GRANT NUMBER W81XWH-14-1-0433 5c. PROGRAM...chloride co-transporters that control EGABA could be used as a corrective strategy for the synaptic and circuit disruptions demonstrated in the

  9. Lactoferricin B-derived peptides with inhibitory effects on ECE-dependent vasoconstriction.

    Science.gov (United States)

    Fernández-Musoles, Ricardo; López-Díez, José Javier; Torregrosa, Germán; Vallés, Salvador; Alborch, Enrique; Manzanares, Paloma; Salom, Juan B

    2010-10-01

    Endothelin-converting enzyme (ECE), a key peptidase in the endothelin (ET) system, cleaves inactive big ET-1 to produce active ET-1, which binds to ET(A) receptors to exert its vasoconstrictor and pressor effects. ECE inhibition could be beneficial in the treatment of hypertension. In this study, a set of eight lactoferricin B (LfcinB)-derived peptides, previously characterized in our laboratory as angiotensin-converting enzyme (ACE) inhibitory peptides, was examined for their inhibitory effects on ECE. In vitro inhibitory effects on ECE activity were assessed using both the synthetic fluorogenic peptide substrate V (FPS V) and the natural substrate big ET-1. To study vasoactive effects, an ex vivo functional assay was developed using isolated rabbit carotid artery segments. With FPS V, only four LfcinB-derived peptides induced inhibition of ECE activity, whereas the eight peptides showed ECE inhibitory effects with big ET-1 as substrate. Regarding the ex vivo assays, six LfcinB-derived peptides showed inhibition of big ET-1-induced, ECE-dependent vasoconstriction. A positive correlation between the inhibitory effects of LfcinB-derived peptides on ECE activity when using big ET-1 and the inhibitory effects on ECE-dependent vasoconstriction was shown. ECE-independent vasoconstriction induced by ET-1 was not affected, thus discarding effects of LfcinB-derived peptides on ET(A) receptors or intracellular signal transduction mechanisms. In conclusion, a combined in vitro and ex vivo method to assess the effects of potentially antihypertensive peptides on the ET system has been developed and applied to show the inhibitory effects on ECE-dependent vasoconstriction of six LfcinB-derived peptides, five of which were dual vasopeptidase (ACE/ECE) inhibitors. Copyright © 2010 Elsevier Inc. All rights reserved.

  10. Testosterone 5alpha-reductase inhibitory active constituents of Piper nigrum leaf.

    Science.gov (United States)

    Hirata, Noriko; Tokunaga, Masashi; Naruto, Shunsuke; Iinuma, Munekazu; Matsuda, Hideaki

    2007-12-01

    Previously we reported that Piper nigrum leaf extract showed a potent stimulation effect on melanogenesis and that (-)-cubebin (1) and (-)-3,4-dimethoxy-3,4-desmethylenedioxycubebin (2) were isolated as active constituents. As a part of our continuous studies on Piper species for the development of cosmetic hair-care agents, testosterone 5alpha-reductase inhibitory activity of aqueous ethanolic extracts obtained from several different parts of six Piper species, namely Piper nigrum, P. methysticum, P. betle, P. kadsura, P. longum, and P. cubeba, were examined. Among them, the extracts of P. nigrum leaf, P. nigrum fruit and P. cubeba fruit showed potent inhibitory activity. Activity-guided fractionation of P. nigrum leaf extract led to the isolation of 1 and 2. Fruits of P. cubeba contain 1 as a major lignan, thus inhibitory activity of the fruit may be attributable to 1. As a result of further assay on other known constituents of the cited Piper species, it was found that piperine, a major alkaloid amide of P. nigrum fruit, showed potent inhibitory activity, thus a part of the inhibitory activity of P. nigrum fruit may depend on piperine. The 5alpha-reductase inhibitory activities of 1 and piperine were found for the first time. In addition, the P. nigrum leaf extract showed in vivo anti-androgenic activity using the hair regrowth assay in testosterone sensitive male C57Black/6CrSlc strain mice.

  11. Preparation of ACE Inhibitory Peptides from Mytilus coruscus Hydrolysate Using Uniform Design

    Directory of Open Access Journals (Sweden)

    Jin-Chao Wu

    2013-01-01

    Full Text Available The angiotensin-I-converting enzyme (ACE inhibitory peptides from mussel, Mytilus coruscus, were investigated and the variable factors, protease concentration, hydrolysis time, pH, and temperature, were optimized using Uniform Design, a new statistical experimental method. The results proved that the hydrolysate of alkali proteases had high ACE-inhibitory activity, especially the alkali protease E1. Optimization by Uniform Design showed that the best hydrolysis conditions for preparation of ACE-inhibitory peptides from Mytilus coruscus were protease concentration of 36.0 U/mL, hydrolysis time of 2.7 hours, pH 8.2, and Temperature at 59.5°C, respectively. The verification experiments under optimum conditions showed that the ACE-inhibitory activity (91.3% were agreed closely with the predicted activity of 90.7%. The amino acid composition analysis of Mytilus coruscus ACE-inhibitory peptides proved that it had high percent of lysine, leucine, glycine, aspartic acid, and glutamic acid.

  12. Antioxidant, antimicrobial, cell viability and enzymatic inhibitory of antioxidant polymers as biological macromolecules.

    Science.gov (United States)

    Hashemi Gahruie, Hadi; Niakousari, Mehrdad

    2017-11-01

    Polymeric antioxidants such as Catechinaldehyde Polycondensates, Catechin-acelaldehydepolycondensates, Flavonoid-grafted chitosan fibers, Ferulate hydrogel, Dextran ferulate hydrogel, Starch-quercetin conjugate, Gallic acid- and Caffeic acid-functionalized chitosan, Gallic acid - chitosan conjugate, Poly(rutin), Gallic acid grafted chitosan, Dextran-Catechin Conjugate belong to biological macromolecules. These kinds of compounds have stronger antioxidant potential and pharmacokinetic activities, as compared to similar low molecular weight preservatives. Most of these compounds sources are either antioxidants with low molecules polymerization, or polymers conjugation such as synthetic or natural preservatives. Additives are well known as being an important ingredient of food products due to their strong preservative potential. Many researchers and industries attempt to find synthesize materials with the same antioxidant potential and higher stability than the similar compounds with low molecular weight. Recently, macromolecular antioxidants have received wide attention as food additives and dietary supplements in functional foods. It seems that the main usage of these compounds is in the food packaging industry. Most of these compounds have strong antioxidant, antimicrobial, cell viability and enzymatic inhibitory properties. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Alpha amylase and Alpha glucosidase inhibitory effects of aqueous stem extract of Salacia oblonga and its GC-MS analysis

    Directory of Open Access Journals (Sweden)

    Gladis Raja Malar Chelladurai

    2018-05-01

    Full Text Available ABSTRACT Our present investigation deals with the phytochemical screening, estimation of total flavonoids, terpenoids and tannin contents to evaluate the anti-diabetic activities of Salacia oblonga stem followed by GC-MS analysis. It explores the natural compounds and the potential α-amylase and α-glucosidase inhibitory actions of stem extracts. The aqueous stem extract was selected from other extracts (ethanol, acetone, petroleum ether and chloroform for the in vitro study of anti-diabetic activity by alpha amylase and alpha glucosidase inhibitory assays. The stem extract was also analyzed by gas chromatography mass spectrometry to identify the natural chemical components. Phytochemical analysis of aqueous stem extract showed major classes of secondary metabolites such as phenols, flavonoids, alkaloids, terpenoids, tannins, saponins. The total flavonoid, terpenoid, and tannin contents were quantified as 19.82±0.06 mg QE/g, 96.2±0.20 mg/g and 11.25±0.03 mg TAE/g respectively. The percentage inhibition of assays showed maximum inhibitory effects (59.46±0.04% and 68.51±0.01% at a concentration of 100 mg/mL. The IC50 values of stem extract was found to be 73.56 mg/mL and 80.90 mg/mL for alpha amylase and alpha glucosidase inhibition. Fifteen chemical constituents were found by GC-MS analysis. This study suggest the aqueous stem extract of Salacia oblonga might be considered as potential source of bio active constituents with excellent antidiabetic activity.

  14. Andrographolide sodium bisulphite-induced inactivation of urease: inhibitory potency, kinetics and mechanism.

    Science.gov (United States)

    Mo, Zhi-Zhun; Wang, Xiu-Fen; Zhang, Xie; Su, Ji-Yan; Chen, Hai-Ming; Liu, Yu-Hong; Zhang, Zhen-Biao; Xie, Jian-Hui; Su, Zi-Ren

    2015-07-16

    The inhibitory effect of andrographolide sodium bisulphite (ASB) on jack bean urease (JBU) and Helicobacter pylori urease (HPU) was performed to elucidate the inhibitory potency, kinetics and mechanism of inhibition in 20 mM phosphate buffer, pH 7.0, 2 mM EDTA, 25 °C. The ammonia formations, indicator of urease activity, were examined using modified spectrophotometric Berthelot (phenol-hypochlorite) method. The inhibitory effect of ASB was characterized with IC50 values. Lineweaver-Burk and Dixon plots for JBU inhibition of ASB was constructed from the kinetic data. SH-blocking reagents and competitive active site Ni2+ binding inhibitors were employed for mechanism study. Molecular docking technique was used to provide some information on binding conformations as well as confirm the inhibition mode. The IC50 of ASB against JBU and HPU was 3.28±0.13 mM and 3.17±0.34 mM, respectively. The inhibition proved to be competitive and concentration- dependent in a slow-binding progress. The rapid formation of initial ASB-JBU complex with an inhibition constant of Ki=2.86×10(-3) mM was followed by a slow isomerization into the final complex with an overall inhibition constant of Ki*=1.33×10(-4) mM. The protective experiment proved that the urease active site is involved in the binding of ASB. Thiol reagents (L-cysteine and dithiothreithol) strongly protect the enzyme from the loss of enzymatic activity, while boric acid and fluoride show weaker protection, indicating that the active-site sulfhydryl group of JBU was potentially involved in the blocking process. Moreover, inhibition of ASB proved to be reversible since ASB-inactivated JBU could be reactivated by dithiothreitol application. Molecular docking assay suggested that ASB made contacts with the important sulfhydryl group Cys-592 residue and restricted the mobility of the active-site flap. ASB was a competitive inhibitor targeting thiol groups of urease in a slow-binding manner both reversibly and concentration

  15. Lactoferricin-related peptides with inhibitory effects on ACE-dependent vasoconstriction.

    Science.gov (United States)

    Centeno, José M; Burguete, María C; Castelló-Ruiz, María; Enrique, María; Vallés, Salvador; Salom, Juan B; Torregrosa, Germán; Marcos, José F; Alborch, Enrique; Manzanares, Paloma

    2006-07-26

    A selection of lactoferricin B (LfcinB)-related peptides with an angiotensin I-converting enzyme (ACE) inhibitory effect have been examined using in vitro and ex vivo functional assays. Peptides that were analyzed included a set of sequence-related antimicrobial hexapeptides previously reported and two representative LfcinB-derived peptides. In vitro assays using hippuryl-L-histidyl-L-leucine (HHL) and angiotensin I as substrates allowed us to select two hexapeptides, PACEI32 (Ac-RKWHFW-NH2) and PACEI34 (Ac-RKWLFW-NH2), and also a LfcinB-derived peptide, LfcinB17-31 (Ac-FKCRRWQWRMKKLGA-NH2). Ex vivo functional assays using rabbit carotid arterial segments showed PACEI32 (both D- and L-enantiomers) and LfcinB17-31 have inhibitory effects on ACE-dependent angiotensin I-induced contraction. None of the peptides exhibited in vitro ACE inhibitory activity using bradykinin as the substrate. In conclusion, three bioactive lactoferricin-related peptides exhibit inhibitory effects on both ACE activity and ACE-dependent vasoconstriction with potential to modulate hypertension that deserves further investigation.

  16. GC-MS Analysis of Fixed Oil from Nelumbo nucifera Gaertn Seeds: Evaluation of Antimicrobial, Antileishmanial and Urease Inhibitory Activities

    International Nuclear Information System (INIS)

    Shahnaz, A.; Khan, H.; Shah, A.; Khan, N.M.

    2016-01-01

    In the present study, chemical composition of fixed oil (NnFO) obtained from Nelumbo nucifera seeds was determined by GC-MS analysis which revealed the presence of 39 compounds mainly comprised of 20.8 % keto fatty acids with high content of methyl ester of palmitic acid (13.59 %) and methyl ester of 9-oxo-nonanoic acid (11.89 %). The other major constituents identified were; fumaric acid-3-methylbut-3-enyl nonyl ester, 2-decenal and methyl ester of 9E-octadecenoic acid as 6.45 %, 5.09 %, 5.06 %, respectively. NnFO along with other fractions were tested for in vitro antimicrobial, antileishmanial and urease inhibitory assays. NnFO showed weak antibacterial activities against the tested bacteria while promising antifungal effect against Candida albicans (68 %), Candida glaberata (65 %) and Aspergillus flavus (64 %). NnFO showed strong antileishmanial activity with IC50 = 7.34 ±0.72 as compared to reference drug (5.1± 0.29) probably due to the presence of keto-ene derivatives. NnFO showed weak urease inhibitory activity while the ethyl acetate fraction (N3) strongly inhibited both J.B. urease (IC50= 21.45 %) and B.P. urease (IC50= 28.65%) respectively. In conclusion, N. nucifera seeds fixed oil possess promising therapeutic potential as a new antifungal and antileishmanial agent. (author)

  17. Regulating prefrontal cortex activation: an emerging role for the 5-HT₂A serotonin receptor in the modulation of emotion-based actions?

    Science.gov (United States)

    Aznar, Susana; Klein, Anders B

    2013-12-01

    The prefrontal cortex (PFC) is involved in mediating important higher-order cognitive processes such as decision making, prompting thereby our actions. At the same time, PFC activation is strongly influenced by emotional reactions through its functional interaction with the amygdala and the striatal circuitry, areas involved in emotion and reward processing. The PFC, however, is able to modulate amygdala reactivity via a feedback loop to this area. A role for serotonin in adjusting for this circuitry of cognitive regulation of emotion has long been suggested based primarily on the positive pharmacological effect of elevating serotonin levels in anxiety regulation. Recent animal and human functional magnetic resonance studies have pointed to a specific involvement of the 5-hydroxytryptamine (5-HT)2A serotonin receptor in the PFC feedback regulatory projection onto the amygdala. This receptor is highly expressed in the prefrontal cortex areas, playing an important role in modulating cortical activity and neural oscillations (brain waves). This makes it an interesting potential pharmacological target for the treatment of neuropsychiatric modes characterized by lack of inhibitory control of emotion-based actions, such as addiction and other impulse-related behaviors. In this review, we give an overview of the 5-HT2A receptor distribution (neuronal, intracellular, and anatomical) along with its functional and physiological effect on PFC activation, and how that relates to more recent findings of a regulatory effect of the PFC on the emotional control of our actions.

  18. Cadmium action in synapses in the brain

    International Nuclear Information System (INIS)

    Minami, Akira; Takeda, Atsushi; Nishibaba, Daisuke; Tekefuta, Sachiyo; Oku, Naoto

    2001-01-01

    Chronic exposure to cadmium causes central nervous system disorders, e.g., olfactory dysfunction. To clarify cadmium toxicity in synaptic neurotransmission in the brain, the movement and action of cadmium in the synapses was examined using in vivo microdialysis. One and 24 h after injection of 109 CdCl 2 into the amygdala of rats, 109 Cd release into the extracellular space was facilitated by stimulation with high K + , suggesting that cadmium taken up in amygdalar neurons is released into the synaptic clefts in a calcium- and impulse-dependent manner. To examine the action of cadmium in the synapses, the amygdala was perfused with artificial cerebrospinal fluid containing 10-30 μM CdCl 2 . The release of excitatory neurotransmitters, i.e., glutamate and aspartate, into the extracellular space was decreased during perfusion with cadmium, while the release of inhibitory neurotransmitters, i.e., glycine and γ-amino butyric acid (GABA), into the extracellular space was increased during the period. These results suggest that cadmium released from the amygdalar neuron terminals affects the degree and balance of excitation-inhibition in synaptic neurotransmission. (author)

  19. Modifying Yeast Tolerance to Inhibitory Conditions of Ethanol Production Processes

    DEFF Research Database (Denmark)

    Caspeta, Luis; Castillo, Tania; Nielsen, Jens

    2015-01-01

    Saccharomyces cerevisiae strains having a broad range of substrate utilization, rapid substrate consumption, and conversion to ethanol, as well as good tolerance to inhibitory conditions are ideal for cost-competitive ethanol production from lignocellulose. A major drawback to directly design S....... cerevisiae tolerance to inhibitory conditions of lignocellulosic ethanol production processes is the lack of knowledge about basic aspects of its cellular signaling network in response to stress. Here, we highlight the inhibitory conditions found in ethanol production processes, the targeted cellular...... functions, the key contributions of integrated -omics analysis to reveal cellular stress responses according to these inhibitors, and current status on design-based engineering of tolerant and efficient S. cerevisiae strains for ethanol production from lignocellulose....

  20. Distinguishing between impairments of working memory and inhibitory control in cases of early dementia.

    Science.gov (United States)

    Crawford, Trevor J; Higham, Steve

    2016-01-29

    Dementia (most notably, Alzheimer's Disease) is often associated with impairments of both working memory and inhibitory control. However, it is unclear whether these are functionally distinct impairments. We addressed the issue of whether working memory and inhibitory control can be dissociated, using data from a sample of patients who were recruited in a longitudinal study (Crawford et al., 2013, 2015). The first case revealed a preserved working memory capacity together with poor inhibitory control in the anti-saccade task. A longitudinal follow-up revealed that the defective inhibitory control emerged 12-months before the dementia was evident on the mini-mental state examination assessment. A second case revealed a poor working memory together with a well-preserved level of inhibitory control. The dissociation of working memory and inhibitory control was confirmed statistically in 7 additional cases. These findings yield converging evidence that working memory and inhibitory control are distinct cognitive operations and challenges the Kimberg and Farah (2000) cognitive model of working memory. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. The Perception-Action Model

    DEFF Research Database (Denmark)

    Grünbaum, Thor

    2017-01-01

    Milner and Goodale’s Two Visual Systems Hypothesis (TVSH) is regarded as common ground in recent discussions of visual consciousness. A central part of TVSH is a functional model of vision and action (a functional perception-action model, PAM for short). In this paper, I provide a brief overview...... of these current discussions and argue that PAM is ambiguous between a strong and a weak version. I argue that, given a standard way of individuating computational mechanisms, the available evidence cannot be used to distinguish between these versions. This not only has consequences for philosophical theories...

  2. Insulin sensitizing and alpha-glucoamylase inhibitory action of sennosides, rheins and rhaponticin in Rhei Rhizoma.

    Science.gov (United States)

    Choi, Soo Bong; Ko, Byoung Seob; Park, Seong Kyu; Jang, Jin Sun; Park, Sunmin

    2006-01-25

    Extracts from Rhei Rhizoma extracts (RR) have been reported to attenuate metabolic disorders such as diabetic nephropathy, hypercholesterolemia and platelet aggregation. With this study we investigated the anti-diabetic action of 70% ethanol RR extract in streptozotocin-induced diabetic mice, and determined the action mechanism of active compounds of RR in vitro. In the diabetic mice, serum glucose levels at fasting and post-prandial states and glucose area under the curve at modified oral glucose tolerance tests were lowered without altering serum insulin levels, indicating that RR contained potential anti-diabetic agents. The fractions fractionated from RR extracts by XAD-4 column revealed that 60%, 80% and 100% methanol fractions enhanced insulin sensitivity and inhibited alpha-glucoamylase activity. The major compounds of these fractions were sennosides, rhein and rhaponticin. Rhaponticin and rhein enhanced insulin-stimulated glucose uptake in 3T3-L1 adipocytes. Rhaponticin increased adipocytes with a differentiating effect similar to pioglitazone, but rhein and sennoside B decreased triglyceride accumulation. Sennoside A and B inhibited alpha-glucoamylase activity as much as acarbose. In conclusion, a crude extract of RR improves glucose intolerance by enhancing insulin-stimulated glucose uptake and decreasing carbohydrate digestion via inhibiting alpha-glucoamylase activity. Rhein and rhaponticin are potential candidates for hypoglycemic agents.

  3. Inhibitory effect of corn silk on skin pigmentation.

    Science.gov (United States)

    Choi, Sang Yoon; Lee, Yeonmi; Kim, Sung Soo; Ju, Hyun Min; Baek, Ji Hwoon; Park, Chul-Soo; Lee, Dong-Hyuk

    2014-03-03

    In this study, the inhibitory effect of corn silk on melanin production was evaluated. This study was performed to investigate the inhibitory effect of corn silk on melanin production in Melan-A cells by measuring melanin production and protein expression. The corn silk extract applied on Melan-A cells at a concentration of 100 ppm decreased melanin production by 37.2% without cytotoxicity. This was a better result than arbutin, a positive whitening agent, which exhibited a 26.8% melanin production inhibitory effect at the same concentration. The corn silk extract did not suppress tyrosinase activity but greatly reduced the expression of tyrosinase in Melan-A cells. In addition, corn silk extract was applied to the human face with hyperpigmentation, and skin color was measured to examine the degree of skin pigment reduction. The application of corn silk extract on faces with hyperpigmentation significantly reduced skin pigmentation without abnormal reactions. Based on the results above, corn silk has good prospects for use as a material for suppressing skin pigmentation.

  4. Inhibitory Effect of Corn Silk on Skin Pigmentation

    Directory of Open Access Journals (Sweden)

    Sang Yoon Choi

    2014-03-01

    Full Text Available In this study, the inhibitory effect of corn silk on melanin production was evaluated. This study was performed to investigate the inhibitory effect of corn silk on melanin production in Melan-A cells by measuring melanin production and protein expression. The corn silk extract applied on Melan-A cells at a concentration of 100 ppm decreased melanin production by 37.2% without cytotoxicity. This was a better result than arbutin, a positive whitening agent, which exhibited a 26.8% melanin production inhibitory effect at the same concentration. The corn silk extract did not suppress tyrosinase activity but greatly reduced the expression of tyrosinase in Melan-A cells. In addition, corn silk extract was applied to the human face with hyperpigmentation, and skin color was measured to examine the degree of skin pigment reduction. The application of corn silk extract on faces with hyperpigmentation significantly reduced skin pigmentation without abnormal reactions. Based on the results above, corn silk has good prospects for use as a material for suppressing skin pigmentation.

  5. Research on Condition Assessment Method of Transmission Tower Under the Action of Strong Wind

    Science.gov (United States)

    Huang, Ren-mou; An, Li-qiang; Zhang, Rong-lun; Wu, Jiong; Liang, Ya-feng

    2018-03-01

    Transmission towers are often subjected to the external damage of severe weather like strong wind and so on, which may cause the collapse due to the yield and fracture of the tower material. Aiming this issue, an assessment method was proposed in this paper to assess the operation condition of transmission towers under strong wind. With a reasonable assess index system established firstly, then the internal force of the tower material was solved and its stability was determined through the mechanical analysis of the transmission tower finite element model. Meanwhile, the condition risk level of the tower was finally determined by considering the difference among the influences of other factors like corrosion and loose of members, slope on the transmission tower through the analytic hierarchy process. The assessment method was applied to assess the wind-induced collapse of towers in 110kV Bao Yi II line in Wenchang City, Hainan Province, of which the result proves the method can assess the condition of transmission tower under strong wind and of guiding significance for improving the windproof capability of transmission towers.

  6. Phytochemical screening and in vitro acetylcholinesterase inhibitory ...

    African Journals Online (AJOL)

    Phytochemical screening and in vitro acetylcholinesterase inhibitory activity of seven plant extracts. Titilayo Johnson, Oduje A. Akinsanmi, Enoch J. Banbilbwa, Tijani A. Yahaya, Karima Abdulaziz, Kolade Omole ...

  7. The Effect of Domestication on Inhibitory Control: Wolves and Dogs Compared

    Science.gov (United States)

    Marshall-Pescini, Sarah; Virányi, Zsófia; Range, Friederike

    2015-01-01

    Inhibitory control i.e. blocking an impulsive or prepotent response in favour of a more appropriate alternative, has been suggested to play an important role in cooperative behaviour. Interestingly, while dogs and wolves show a similar social organization, they differ in their intraspecific cooperation tendencies in that wolves rely more heavily on group coordination in regard to hunting and pup-rearing compared to dogs. Hence, based on the ‘canine cooperation’ hypothesis wolves should show better inhibitory control than dogs. On the other hand, through the domestication process, dogs may have been selected for cooperative tendencies towards humans and/or a less reactive temperament, which may in turn have affected their inhibitory control abilities. Hence, based on the latter hypothesis, we would expect dogs to show a higher performance in tasks requiring inhibitory control. To test the predictive value of these alternative hypotheses, in the current study two tasks; the ‘cylinder task’ and the ‘detour task’, which are designed to assess inhibitory control, were used to evaluate the performance of identically raised pack dogs and wolves. Results from the cylinder task showed a significantly poorer performance in wolves than identically-raised pack dogs (and showed that pack-dogs performed similarly to pet dogs with different training experiences), however contrary results emerged in the detour task, with wolves showing a shorter latency to success and less perseverative behaviour at the fence. Results are discussed in relation to previous studies using these paradigms and in terms of the validity of these two methods in assessing inhibitory control. PMID:25714840

  8. Inhibitory control and moral emotions: relations to reparation in early and middle childhood.

    Science.gov (United States)

    Colasante, Tyler; Zuffianò, Antonio; Bae, Na Young; Malti, Tina

    2014-01-01

    This study examined links between inhibitory control, moral emotions (sympathy and guilt), and reparative behavior in an ethnically diverse sample of 4- and 8-year-olds (N = 162). Caregivers reported their children's reparative behavior, inhibitory control, and moral emotions through a questionnaire, and children reported their guilt feelings in response to a series of vignettes depicting moral transgressions. A hypothesized meditation model was tested with inhibitory control relating to reparative behavior through sympathy and guilt. In support of this model, results revealed that high levels of inhibitory control were associated with high levels of reparative behavior through high levels of sympathy and guilt. However, the mediation of inhibitory control to reparation through guilt was significant for 4-year-olds only. Results are discussed in relation to the temperamental, regulatory, and affective-moral precursors of reparative behavior in early and middle childhood.

  9. Hunger, inhibitory control and distress-induced emotional eating.

    Science.gov (United States)

    van Strien, Tatjana; Ouwens, Machteld A; Engel, Carmen; de Weerth, Carolina

    2014-08-01

    Self-reported emotional eating has been found to significantly moderate distress-induced food intake, with low emotional eaters eating less after a stress task than after a control task and high emotional eaters eating more. The aim of the present study was to explore possible underlying mechanisms by assessing possible associations with (1) ability to experience the typical post-stress reduction of hunger and (2) inhibitory control. We studied these effects in 54 female students who were preselected on the basis of extremely high or low scores on an emotional eating questionnaire. Using a within subject design we measured the difference of actual food or snack intake after a control or a stress task (Trier Social Stress Test). As expected, the moderator effect of emotional eating on distress-induced food intake was found to be only present in females with a failure to report the typical reduction of hunger immediately after a stress task (an a-typical hunger stress response). Contrary to our expectations, this moderator effect of emotional eating was also found to be only present in females with high ability to stop motor impulses (high inhibitory control). These findings suggest that an a-typical hunger stress response but not poor inhibitory control may underlie the moderator effect of emotional eating on distress-induced food intake. However, inhibitory control may play a role whether or not there is a moderator effect of self-reported emotional eating on distress-induced food intake. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Novel modulatory effects of neurosteroids and benzodiazepines on excitatory and inhibitory neurons excitability: a multi-electrode array (MEA recording study"

    Directory of Open Access Journals (Sweden)

    Giulia ePuia

    2012-11-01

    Full Text Available The balance between glutamate- and GABA-mediated neurotransmission in the brain is fundamental in the nervous system, but it is regulated by the ‘tonic’ release of a variety of endogenous factors. One such important group of molecules are the neurosteroids (NSs which, similarly to benzodiazepines (BDZs, enhance GABAergic neurotransmission. The purpose of our work was to investigate, at in-vivo physiologically relevant concentrations, the effects of NSs and BDZs as GABA modulators on dissociated neocortical neuron networks grown in long-term culture. We used a multi-electrode array (MEA recording technique and a novel analysis that was able to both identify the action potentials of engaged excitatory and inhibitory neurons and to detect drug-induced network up-states (burst. We found that the NSs tetrahydrodeoxycorticosterone (THDOC and allopregnanolone (ALLO applied at low nM concentrations, produced different modulatory effects on the two neuronal clusters. Conversely, at high concentrations (1 µM, both NSs, decreased excitatory and inhibitory neuron cluster excitability; however, even several hours after washout, the excitability of inhibitory neurons continued to be depressed, leading to a network long term depression (LTD. The BDZs clonazepam (CLZ and midazolam (MDZ also decreased the network excitability, but only MDZ caused LTD of inhibitory neuron cluster. To investigate the origin of the LTD after MDZ application, we tested finasteride (FIN, an inhibitor of endogenous NSs synthesis. FIN did not prevent the LTD induced by MDZ, but surprisingly induced it after application of CLZ. The significance and possible mechanisms underlying these LTD effects of NSs and BDZs are discussed. Taken together, our results not only demonstrate that ex-vivo networks show a sensitivity to NSs and BDZs comparable to that expressed in vivo, but also provide a new global in-vitro description that can help in understanding their activity in more complex

  11. Topical glucocorticoids and the skin-mechanisms of action: an update

    Directory of Open Access Journals (Sweden)

    A. Ahluwalia

    1998-01-01

    Full Text Available The topical glucocorticoids (GCs represent the treatment of choice for many types of inflammatory dermatoses. Despite the extensive use of this class of drugs as first line therapy the mechanism of their action is uncertain. It is clear that the multiplicity of actions of the topical GCs is an important facet of their scope in the treatment of dermal disorders. The aim of this update is to review past and current theories regarding how these agents might work. Current understanding of the molecular mechanism s of GC action has advanced significantly over the past decade with the realisation that multiple systems are responsible for transduction of GC effects at a molecular level. The two primary modes of action are via interaction directly with DNA or indirectly through modulation of specific transcription factors: the endpoint in both cases being modulation of specific protein synthesis. Both of these mechanisms will be discussed. In particular this review will concentrate on the possibility that a GC-inducible protein, termed lipocortin 1, may have a significant role to play in the anti-inflammatory actions of these drugs. Additionally it has become apparent that several inflammatory enzymes induced in inflamm ation are sites of inhibitory action of the GCs, and the possibility that this occurs in the skin will be discussed paying particular attention to the inducible phospholipase A2, nitric oxide synthase and cyclooxygenase systems.

  12. A virtual screening method for inhibitory peptides of Angiotensin I-converting enzyme.

    Science.gov (United States)

    Wu, Hongxi; Liu, Yalan; Guo, Mingrong; Xie, Jingli; Jiang, XiaMin

    2014-09-01

    Natural small peptides from foods have been proven to be efficient inhibitors of Angiotensin I-converting enzyme (ACE) for the regulation of blood pressure. The traditional ACE inhibitory peptides screening method is both time consuming and money costing, to the contrary, virtual screening method by computation can break these limitations. We establish a virtual screening method to obtain ACE inhibitory peptides with the help of Libdock module of Discovery Studio 3.5 software. A significant relationship between Libdock score and experimental IC(50) was found, Libdock score = 10.063 log(1/IC(50)) + 68.08 (R(2) = 0.62). The credibility of the relationship was confirmed by testing the coincidence of the estimated log(1/IC(50)) and measured log(1/IC(50)) (IC(50) is 50% inhibitory concentration toward ACE, in μmol/L) of 5 synthetic ACE inhibitory peptides, which was virtual hydrolyzed and screened from a kind of seafood, Phascolosoma esculenta. Accordingly, Libdock method is a valid IC(50) estimation tool and virtual screening method for small ACE inhibitory peptides. © 2014 Institute of Food Technologists®

  13. Improving oral bioavailability of resveratrol by a UDP-glucuronosyltransferase inhibitory excipient-based self-microemulsion.

    Science.gov (United States)

    Yang, Fei-Fei; Zhou, Jing; Hu, Xiao; Cong, Zhao-Qing; Liu, Chun-Yu; Pan, Rui-Le; Chang, Qi; Liu, Xin-Min; Liao, Yong-Hong

    2018-03-01

    Self-microemulsifying (SME) drug delivery system has been developed to increase oral bioavailabilities, and inhibitory excipients are capable of improving oral bioavailability by inhibiting enzyme mediated intestinal metabolism. However, the potential of enzyme inhibitory excipients containing SME in boosting resveratrol bioavailability remains largely uninvestigated. In this study, we set out to prepare SME-1 with UGT inhibitory excipients (excipients without inhibitory activities named SME-2 as control) to increase the bioavailability of RES by inhibiting intestinal metabolism. Results demonstrated that similar physicochemical properties such as size, polydistribution index and in vitro release, cellular uptake and permeability in Caco-2 cells as well as in vivo lymphatic distribution between inhibitory SME-1 and non-inhibitory SME-2 were observed. In vivo study demonstrated that the molar ratios of RES-G/RES were 7.25±0.48 and 5.06±2.42 for free drug and SME-2, respectively, and the molar ratio decreased to 0.36±0.10 in SME-1 group. Pharmacokinetic study confirmed that the inhibitory excipients containing SME demonstrated potential in increasing bioavailability of RES from 6.5% for the free RES and 12.9% for SME-2 to 76.1% in SME-1 through modulating the glucuronidation by UGT inhibitory excipients. Copyright © 2018 Elsevier B.V. All rights reserved.

  14. Optimization of inhibitory decision rules relative to length and coverage

    KAUST Repository

    Alsolami, Fawaz

    2012-01-01

    The paper is devoted to the study of algorithms for optimization of inhibitory rules relative to the length and coverage. In contrast with usual rules that have on the right-hand side a relation "attribute ≠ value", inhibitory rules have a relation "attribute = value" on the right-hand side. The considered algorithms are based on extensions of dynamic programming. © 2012 Springer-Verlag.

  15. Inhibitory Synaptic Plasticity - Spike timing dependence and putative network function.

    Directory of Open Access Journals (Sweden)

    Tim P Vogels

    2013-07-01

    Full Text Available While the plasticity of excitatory synaptic connections in the brain has been widely studied, the plasticity of inhibitory connections is much less understood. Here, we present recent experimental and theoretical □ndings concerning the rules of spike timing-dependent inhibitory plasticity and their putative network function. This is a summary of a workshop at the COSYNE conference 2012.

  16. Modifying yeast tolerance to inhibitory conditions of ethanol production processes

    Directory of Open Access Journals (Sweden)

    Luis eCaspeta

    2015-11-01

    Full Text Available Saccharomyces cerevisiae strains having a broad range of substrate utilization, rapid substrate consumption and conversion to ethanol, as well as good tolerance to inhibitory conditions are ideal for cost-competitive ethanol production from lignocellulose. A major drawback to directly design S. cerevisiae tolerance to inhibitory conditions of lignocellulosic ethanol production processes is the lack of knowledge about basic aspects of its cellular signaling network in response to stress. Here we highlight the inhibitory conditions found in ethanol production processes, the targeted cellular functions, the key contributions of integrated –omics analysis to reveal cellular stress responses according to these inhibitors, and current status on design-based engineering of tolerant and efficient S. cerevisiae strains for ethanol production from lignocellulose.

  17. Antioxidant and inhibitory properties of Clerodendrum volubile leaf extracts on key enzymes relevant to non-insulin dependent diabetes mellitus and hypertension

    Directory of Open Access Journals (Sweden)

    Stephen A. Adefegha

    2016-07-01

    Conclusion: The inhibitory properties of phenolic rich extracts on α-amylase, α-glucosidase, ACE, and Fe2+- and sodium nitroprusside-induced lipid peroxidation in the pancreas could be attributed to the antioxidant properties of the extracts and their phenolic composition. The stronger action of the bound phenolic extract on α-glucosidase may provide the possible bioactivity at the brush border end of the intestinal wall. This study may thus suggest that leaves represent a functional food and nutraceutical in the management of non-insulin dependent diabetes mellitus and hypertension.

  18. Inhibitory serum factor of lymphoproliferative response to allogeneic cells in pregnancy

    Directory of Open Access Journals (Sweden)

    Silvia Daher

    Full Text Available INTRODUCTION: An inhibitory serum factor of mixed lymphocyte culture (MLC has been associated with successful pregnancy after lymphocyte transfusion in women with unexplained recurrent spontaneous abortions (RSA. OBJECTIVE: Investigate whether the inhibitory serum factor of MLC is essential for a successful pregnancy. METHOD: Sera from 33 healthy pregnant women and from 40 women with RSA were assessed by a one-way MLC in which the woman's lymphocytes were stimulated with her partner's lymphocytes or with third party lymphocytes. RESULTS: An inhibitory serum effect (inhibition > 50% as compared to normal serum was detected in 45% of the pregnant women who had at least 1 previous parity, in 8% of the primigravidea, in 29% of those with one abortion and in 58% of those with more than one abortion. CONCLUSION: MLC inhibitory serum factor does not seem to be an essential factor for pregnancy development. Therefore, it should not be considered as a parameter for the assessment of RSA patients.

  19. Inhibitory effects of crude extracts from several plants on postharvest pathogens of citrus

    Science.gov (United States)

    Gong, Mingfu; Guan, Qinlan; Xu, Shanshan

    2018-04-01

    China is one of the most important origin of citrus. Enormous economic losses was caused by fungal diseases in citrus harvest storage every year. The effective antimicrobial substances of garlic, ginger, celery and pepper were extracted by ethanol extraction and water extraction respectively. The inhibitory effects of the crude extract on Penicillium sp. caused fungal diseases in citrus harvest storage were also determined. The results showed that the extracts of garlic, ginger and celery had inhibitory effect on P. sp., but the extracts of pepper had no inhibitory effect on P. sp.. The garlic ethanol extracts had the best inhibitory effect on P. citrinum.

  20. Reducing Weak to Strong Bisimilarity in CCP

    Directory of Open Access Journals (Sweden)

    Andrés Aristizábal

    2012-12-01

    Full Text Available Concurrent constraint programming (ccp is a well-established model for concurrency that singles out the fundamental aspects of asynchronous systems whose agents (or processes evolve by posting and querying (partial information in a global medium. Bisimilarity is a standard behavioural equivalence in concurrency theory. However, only recently a well-behaved notion of bisimilarity for ccp, and a ccp partition refinement algorithm for deciding the strong version of this equivalence have been proposed. Weak bisimiliarity is a central behavioural equivalence in process calculi and it is obtained from the strong case by taking into account only the actions that are observable in the system. Typically, the standard partition refinement can also be used for deciding weak bisimilarity simply by using Milner's reduction from weak to strong bisimilarity; a technique referred to as saturation. In this paper we demonstrate that, because of its involved labeled transitions, the above-mentioned saturation technique does not work for ccp. We give an alternative reduction from weak ccp bisimilarity to the strong one that allows us to use the ccp partition refinement algorithm for deciding this equivalence.

  1. NK cell activation: distinct stimulatory pathways counterbalancing inhibitory signals.

    Science.gov (United States)

    Bakker, A B; Wu, J; Phillips, J H; Lanier, L L

    2000-01-01

    A delicate balance between positive and negative signals regulates NK cell effector function. Activation of NK cells may be initiated by the triggering of multiple adhesion or costimulatory molecules, and can be counterbalanced by inhibitory signals induced by receptors for MHC class I. A common pathway of inhibitory signaling is provided by immunoreceptor tyrosine-based inhibitory motifs (ITIMs) in the cytoplasmic domains of these receptors which mediate the recruitment of SH2 domain-bearing tyrosine phosphate-1 (SHP-1). In contrast to the extensive progress that has been made regarding the negative regulation of NK cell function, our knowledge of the signals that activate NK cells is still poor. Recent studies of the activating receptor complexes have shed new light on the induction of NK cell effector function. Several NK receptors using novel adaptors with immunoreceptor tyrosine-based activation motifs (ITAMs) and with PI 3-kinase recruiting motifs have been implicated in NK cell stimulation.

  2. On minimal inhibitory rules for almost all k-valued information systems

    KAUST Repository

    Moshkov, Mikhail

    2009-07-30

    The minimal inhibitory rules for information systems can be used for construction of classifiers. We show that almost all information systems from a certain large class of information systems have relatively short minimal inhibitory rules. However, the number of such rules is not polynomial in the number of attributes and the number of objects. This class consists of all k-valued information systems, k ≥ 2, with the number of objects polynomial in the number of attributes. Hence, for efficient construction of classifiers some filtration techniques in rule generation are necessary. Another way is to work with lazy classification algorithms based on inhibitory rules.

  3. Dissociable Fronto-Operculum-Insula Control Signals for Anticipation and Detection of Inhibitory Sensory Cue.

    Science.gov (United States)

    Cai, Weidong; Chen, Tianwen; Ide, Jaime S; Li, Chiang-Shan R; Menon, Vinod

    2017-08-01

    The ability to anticipate and detect behaviorally salient stimuli is important for virtually all adaptive behaviors, including inhibitory control that requires the withholding of prepotent responses when instructed by external cues. Although right fronto-operculum-insula (FOI), encompassing the anterior insular cortex (rAI) and inferior frontal cortex (rIFC), involvement in inhibitory control is well established, little is known about signaling mechanisms underlying their differential roles in detection and anticipation of salient inhibitory cues. Here we use 2 independent functional magnetic resonance imaging data sets to investigate dynamic causal interactions of the rAI and rIFC, with sensory cortex during detection and anticipation of inhibitory cues. Across 2 different experiments involving auditory and visual inhibitory cues, we demonstrate that primary sensory cortex has a stronger causal influence on rAI than on rIFC, suggesting a greater role for the rAI in detection of salient inhibitory cues. Crucially, a Bayesian prediction model of subjective trial-by-trial changes in inhibitory cue anticipation revealed that the strength of causal influences from rIFC to rAI increased significantly on trials in which participants had higher anticipation of inhibitory cues. Together, these results demonstrate the dissociable bottom-up and top-down roles of distinct FOI regions in detection and anticipation of behaviorally salient cues across multiple sensory modalities. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  4. Anti-Staphylococcus aureus action of three Caatinga fruits evaluated by electron microscopy.

    Science.gov (United States)

    da Silva, Luís Cláudio Nascimento; Sandes, Jana Messias; de Paiva, Maurício Magalhães; de Araújo, Janete Magali; de Figueiredo, Regina Célia Bressan Queiroz; da Silva, Márcia Vanusa; Correia, Maria Tereza dos Santos

    2013-01-01

    This study evaluated the antibacterial activity of Anadenanthera colubrina, Libidibia ferrea and Pityrocarpa moniliformis fruit extracts against clinical strains of Staphylococcus aureus. The samples were active for all S. aureus strains (minimum inhibitory concentration: 0.38-3.13 mg mL⁻¹), including the multiresistant strain. The morphological changes suggested the cell wall as the main action target. The treated-cells also lose their ability to form aggregates. The analysis suggests cell wall impairment, which causes the loss of viability and death. This study showed for the first time the morphologic alterations involved in the anti-S. aureus action of fruits of A. colubrina, L. ferrea and P. moniliformis. These findings indicated that these fruit extracts are sources of bioactive compounds that can be used as antibacterial agents.

  5. Understanding communicative actions: a repetitive TMS study.

    Science.gov (United States)

    Stolk, Arjen; Noordzij, Matthijs L; Volman, Inge; Verhagen, Lennart; Overeem, Sebastiaan; van Elswijk, Gijs; Bloem, Bas; Hagoort, Peter; Toni, Ivan

    2014-02-01

    Despite the ambiguity inherent in human communication, people are remarkably efficient in establishing mutual understanding. Studying how people communicate in novel settings provides a window into the mechanisms supporting the human competence to rapidly generate and understand novel shared symbols, a fundamental property of human communication. Previous work indicates that the right posterior superior temporal sulcus (pSTS) is involved when people understand the intended meaning of novel communicative actions. Here, we set out to test whether normal functioning of this cerebral structure is required for understanding novel communicative actions using inhibitory low-frequency repetitive transcranial magnetic stimulation (rTMS). A factorial experimental design contrasted two tightly matched stimulation sites (right pSTS vs left MT+, i.e., a contiguous homotopic task-relevant region) and tasks (a communicative task vs a visual tracking task that used the same sequences of stimuli). Overall task performance was not affected by rTMS, whereas changes in task performance over time were disrupted according to TMS site and task combinations. Namely, rTMS over pSTS led to a diminished ability to improve action understanding on the basis of recent communicative history, while rTMS over MT+ perturbed improvement in visual tracking over trials. These findings qualify the contributions of the right pSTS to human communicative abilities, showing that this region might be necessary for incorporating previous knowledge, accumulated during interactions with a communicative partner, to constrain the inferential process that leads to action understanding. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. Fungal growth inhibitory properties of new phytosphingolipid analogues.

    Science.gov (United States)

    Mormeneo, D; Manresa, A; Casas, J; Llebaria, A; Delgado, A

    2008-04-01

    To study the growth inhibitory properties of a series of phytosphingosine (PHS) and phytoceramide (PHC) analogues. A panel of two yeast (Candida albicans and Saccharomyces cerevisiae) and six moulds (Aspergillus repens, Aspergillus niger, Penicillium chrysogenum, Cladosporium cladosporioides, Arthroderma uncinatum and Penicillium funiculosum) has been used in this study. A series of new PHS and PHC analogues differing at the sphingoid backbone and the functional group at C1 position were synthesized. Among PHS analogues, 1-azido derivative 1c, bearing the natural D-ribo stereochemistry, showed a promising growth inhibitory profile. Among PHC analogues, compound 12, with a bulky N-pivaloyl group and a Z double bond at C3 position of the sphingoid chain, was the most active growth inhibitor. Minimal inhibitory concentration values were in the range of 23-48 micromol l(-1) for 1c and 44-87 micromol l(-1) for 12. Only scattered data on the antifungal activity of phytosphingolipids have been reported in the literature. This is the first time that a series of analogues of this kind are tested and compared to discern their structural requirements for antifungal activity.

  7. Mechanism of Cancer Growth Suppression of Alpha-Fetoprotein Derived Growth Inhibitory Peptides (GIP): Comparison of GIP-34 versus GIP-8 (AFPep). Updates and Prospects

    Energy Technology Data Exchange (ETDEWEB)

    Mizejewski, Gerald J. [Division of Translational Medicine, Wadsworth Center, New York State Department of Health, Empire State Plaza, Albany, NY 12201 (United States)

    2011-06-20

    The Alpha-fetoprotein (AFP) derived Growth Inhibitory Peptide (GIP) is a 34-amino acid segment of the full-length human AFP molecule that inhibits tumor growth and metastasis. The GIP-34 and its carboxy-terminal 8-mer segment, termed GIP-8, were found to be effective as anti-cancer therapeutic peptides against nine different human cancer types. Following the uptake of GIP-34 and GIP-8 into the cell cytoplasm, each follows slightly different signal transduction cascades en route to inhibitory pathways of tumor cell growth and proliferation. The parallel mechanisms of action of GIP-34 versus GIP-8 are demonstrated to involve interference of signaling transduction cascades that ultimately result in: (1) cell cycle S-phase/G2-phase arrest; (2) prevention of cyclin inhibitor degradation; (3) protection of p53 from inactivation by phosphorylation; and (4) blockage of K{sup +} ion channels opened by estradiol and epidermal growth factor (EGF). The overall mechanisms of action of both peptides are discussed in light of their differing modes of cell attachment and uptake fortified by RNA microarray analysis and electrophysiologic measurements of cell membrane conductance and resistance. As a chemotherapeutic adjunct, the GIPs could potentially aid in alleviating the negative side effects of: (1) tamoxifen resistance, uterine hyperplasia/cancer, and blood clotting; (2) Herceptin antibody resistance and cardiac (arrest) arrhythmias; and (3) doxorubicin's bystander cell toxicity.

  8. Determinants of aggressive behavior: Interactive effects of emotional regulation and inhibitory control.

    Directory of Open Access Journals (Sweden)

    I-Ju Hsieh

    Full Text Available Aggressive behavior can be defined as any behavior intended to hurt another person, and it is associated with many individual and social factors. This study examined the relationship between emotional regulation and inhibitory control in predicting aggressive behavior. Seventy-eight participants (40 males completed self-report measures (Negative Mood Regulation Scale and Buss-Perry Aggression Questionnaire, a stop signal task, and engaged in a modified version of Taylor Aggression Paradigm (TAP exercise, in which the outcome was used as a measure of direct physical aggression. We used a hierarchical, mixed-model multiple regression analysis test to examine the effects of emotion regulation and inhibitory control on physical reactive aggression. Results indicated an interaction between emotion regulation and inhibitory control on aggression. For participants with low inhibitory control only, there was a significant difference between high and low emotion regulation on aggression, such that low emotion regulation participants registered higher aggression than high emotion regulation participants. This difference was not found among participants with high inhibitory control. These results have implications for refining and targeting training and rehabilitation programs aimed at reducing aggressive behavior.

  9. Increased beta rhythm as an indicator of inhibitory mechanisms in tourette syndrome

    DEFF Research Database (Denmark)

    Niccolai, Valentina; van Dijk, Hanneke; Franzkowiak, Stephanie

    2016-01-01

    BACKGROUND: Inhibitory oscillatory mechanisms subserving tic compensation have been put forward in Tourette syndrome. Modulation of the beta rhythm (15-25 Hz) as the well-established oscillatory movement execution-inhibition indicator was tested during a cognitive-motor task in patients with Tour......BACKGROUND: Inhibitory oscillatory mechanisms subserving tic compensation have been put forward in Tourette syndrome. Modulation of the beta rhythm (15-25 Hz) as the well-established oscillatory movement execution-inhibition indicator was tested during a cognitive-motor task in patients...... in parieto-occipital brain regions contralaterally to the response hand. Average beta power and power gain correlated negatively with tic severity. CONCLUSIONS: Increased motor inhibitory as well as visuomotor attentional processes are likely to subserve tic compensation. Correlational results suggest...... that stronger inhibitory compensation accompanies less tic severity. © 2016 International Parkinson and Movement Disorder Society....

  10. Interhemispheric inhibition during mental actions of different complexity.

    Directory of Open Access Journals (Sweden)

    Nicolas Gueugneau

    Full Text Available Several investigations suggest that actual and mental actions trigger similar neural substrates. Yet, neurophysiological evidences on the nature of interhemispheric interactions during mental movements are still meagre. Here, we asked whether the content of mental images, investigated by task complexity, is finely represented in the inhibitory interactions between the two primary motor cortices (M1s. Subjects' left M1 was stimulated by means of transcranial magnetic stimulation (TMS while they were performing actual or mental movements of increasing complexity with their right hand and exerting a maximum isometric force with their left thumb and index. Thus, we simultaneously assessed the corticospinal excitability in the right opponent pollicis muscle (OP and the ipsilateral silent period (iSP in the left OP during actual and mental movements. Corticospinal excitability in right OP increased during actual and mental movements, but task complexity-dependent changes were only observed during actual movements. Interhemispheric motor inhibition in the left OP was similarly modulated by task complexity in both mental and actual movements. Precisely, the duration and the area of the iSP increased with task complexity in both movement conditions. Our findings suggest that mental and actual movements share similar inhibitory neural circuits between the two homologous primary motor cortex areas.

  11. LTS and FS inhibitory interneurons, short-term synaptic plasticity, and cortical circuit dynamics.

    Directory of Open Access Journals (Sweden)

    Itai Hayut

    2011-10-01

    Full Text Available Somatostatin-expressing, low threshold-spiking (LTS cells and fast-spiking (FS cells are two common subtypes of inhibitory neocortical interneuron. Excitatory synapses from regular-spiking (RS pyramidal neurons to LTS cells strongly facilitate when activated repetitively, whereas RS-to-FS synapses depress. This suggests that LTS neurons may be especially relevant at high rate regimes and protect cortical circuits against over-excitation and seizures. However, the inhibitory synapses from LTS cells usually depress, which may reduce their effectiveness at high rates. We ask: by which mechanisms and at what firing rates do LTS neurons control the activity of cortical circuits responding to thalamic input, and how is control by LTS neurons different from that of FS neurons? We study rate models of circuits that include RS cells and LTS and FS inhibitory cells with short-term synaptic plasticity. LTS neurons shift the RS firing-rate vs. current curve to the right at high rates and reduce its slope at low rates; the LTS effect is delayed and prolonged. FS neurons always shift the curve to the right and affect RS firing transiently. In an RS-LTS-FS network, FS neurons reach a quiescent state if they receive weak input, LTS neurons are quiescent if RS neurons receive weak input, and both FS and RS populations are active if they both receive large inputs. In general, FS neurons tend to follow the spiking of RS neurons much more closely than LTS neurons. A novel type of facilitation-induced slow oscillations is observed above the LTS firing threshold with a frequency determined by the time scale of recovery from facilitation. To conclude, contrary to earlier proposals, LTS neurons affect the transient and steady state responses of cortical circuits over a range of firing rates, not only during the high rate regime; LTS neurons protect against over-activation about as well as FS neurons.

  12. Strong cytotoxic effect of the bradykinin antagonist BKM-570 in ovarian cancer cells--analysis of the molecular mechanisms of its antiproliferative action.

    Science.gov (United States)

    Jutras, Stephanie; Bachvarova, Magdalena; Keita, Mamadou; Bascands, Jean-Loup; Mes-Masson, Anne-Marie; Stewart, John M; Gera, Lajos; Bachvarov, Dimcho

    2010-12-01

    The standard chemotherapy for epithelial ovarian cancer (EOC) patients is currently a combination of taxane and platinum. However, most EOC patients still suffer relapses, and there is an immediate need for the development of novel and more effective therapeutic modalities against this deadly disease. Recently, the nonpeptide bradykinin (BK) antagonist 2,3,4,5,6-pentafluorocinnamoyl-(o-2,6-dichlorobenzyl)-l-tyrosine-N-(4-amino-2,2,6,6-tetramethyl-piperidyl) amide (BKM-570) was shown to cause impressive growth inhibition of lung and prostate tumors, displaying superior in vivo inhibitory effects than convential chemotherapeutic drugs. Here, we investigated BKM-570 cytotoxic effects in two EOC cell lines, derived from different EOC histopathologies: a clear cell carcinoma (TOV-21), and an endometrioid carcinoma (TOV-112). We showed that BKM-570 effectively inhibited the growth of ovarian cancer cells, as its cytotoxic effects were comparable to those of cisplatin, and were independent of the functional status of BK receptors. Moreover, BKM-570 synergized with cisplatin in inhibiting EOC cell growth. To better understand the molecular mechanisms of the antiproliferative action of this BK antagonist in EOC cells, we performed gene expression profiling in TOV-21 and TOV-112 cells following treatment with 10 μM BKM-570 for 24 h. BKM-570 displayed similar cytotoxic effects in the two cell lines analyzed, as genes with previously shown involvement in apoptosis/antiapoptosis and cell adhesion were proportionally upregulated and downregulated in both cell lines, whereas genes involved in basic cellular mechanisms, including cell growth and maintenance, metabolism, cell cycle control, inflammatory and immune response, signal transduction, protein biosynthesis, transcription regulation, and transport, were predominantly downregulated upon treatment. Our data are indicative of the therapeutic potential of BKM-570 and related compounds in EOC management. © 2010 The Authors

  13. College Binge Drinking Associated with Decreased Frontal Activation to Negative Emotional Distractors during Inhibitory Control

    Directory of Open Access Journals (Sweden)

    Julia E. Cohen-Gilbert

    2017-09-01

    Full Text Available The transition to college is associated with an increase in heavy episodic alcohol use, or binge drinking, during a time when the prefrontal cortex and prefrontal-limbic circuitry continue to mature. Traits associated with this immaturity, including impulsivity in emotional contexts, may contribute to risky and heavy episodic alcohol consumption. The current study used blood oxygen level dependent (BOLD multiband functional magnetic resonance imaging (fMRI to assess brain activation during a task that required participants to ignore background images with positive, negative, or neutral emotional valence while performing an inhibitory control task (Go-NoGo. Subjects were 23 college freshmen (seven male, 18–20 years who engaged in a range of drinking behavior (past 3 months’ binge episodes range = 0–19, mean = 4.6, total drinks consumed range = 0–104, mean = 32.0. Brain activation on inhibitory trials (NoGo was contrasted between negative and neutral conditions and between positive and neutral conditions using non-parametric testing (5000 permutations and cluster-based thresholding (z = 2.3, p ≤ 0.05 corrected. Results showed that a higher recent incidence of binge drinking was significantly associated with decreased activation of dorsolateral prefrontal cortex (DLPFC, dorsomedial prefrontal cortex (DMPFC, and anterior cingulate cortex (ACC, brain regions strongly implicated in executive functioning, during negative relative to neutral inhibitory trials. No significant associations between binge drinking and brain activation were observed for positive relative to neutral images. While task performance was not significantly associated with binge drinking in this sample, subjects with heavier recent binge drinking showed decreased recruitment of executive control regions under negative versus neutral distractor conditions. These findings suggest that in young adults with heavier recent binge drinking, processing of negative emotional

  14. Characterisation of inhibitory substances produced by two Pseudoalteromonas species and the cyanobacterial strain Flo1

    OpenAIRE

    Rau, Jan Erik

    2011-01-01

    In the present study the inhibitory substances of P. aurantia NCIMB 2052T and P. citrea NCIMB 1889T were investigated with respect to their substantial and functional nature, their inhibitory potential, their stability against various treatments as well as the growth phases and incubation conditions when the substances are produced. In addition, an inhibitory substance produced by strain Flo1 was examined regarding its structure, function, and inhibitory potential. Furthermore, its taxonomic ...

  15. Sleep: The hebbian reinforcement of the local inhibitory synapses.

    Science.gov (United States)

    Touzet, Claude

    2015-09-01

    Sleep is ubiquitous among the animal realm, and represents about 30% of our lives. Despite numerous efforts, the reason behind our need for sleep is still unknown. The Theory of neuronal Cognition (TnC) proposes that sleep is the period of time during which the local inhibitory synapses (in particular the cortical ones) are replenished. Indeed, as long as the active brain stays awake, hebbian learning guarantees that efficient inhibitory synapses lose their efficiency – just because they are efficient at avoiding the activation of the targeted neurons. Since hebbian learning is the only known mechanism of synapse modification, it follows that to replenish the inhibitory synapses' efficiency, source and targeted neurons must be activated together. This is achieved by a local depolarization that may travel (wave). The period of time during which such slow waves are experienced has been named the "slow-wave sleep" (SWS). It is cut into several pieces by shorter periods of paradoxical sleep (REM) which activity resembles that of the awake state. Indeed, SWS – because it only allows local neural activation – decreases the excitatory long distance connections strength. To avoid losing the associations built during the awake state, these long distance activations are played again during the REM sleep. REM and SWS sleeps act together to guarantee that when the subject awakes again, his inhibitory synaptic efficiency is restored and his (excitatory) long distance associations are still there. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Preparing hearts and minds: cardiac slowing and a cortical inhibitory network.

    Science.gov (United States)

    Jennings, J R; van der Molen, M W; Tanase, C

    2009-11-01

    Preparing for a cued, speeded response induces a set of physiological changes. A review of the psychophysiology of preparation suggested that inhibition of action was an important process among the constellation of changes constituting attentive preparation. The current experiment combined event-related functional magnetic resonance imaging and cardiac inter-beat interval measures in an experiment that compared preparing for a response, watching stimuli without responding, and responding in the absence of preparation. Ten college-aged participants were tested in an initial psychophysiological experiment followed by two scanning sessions during which reverse spiral imaging was performed concurrent with inter-beat interval measurement. Two analytic approaches were used to confirm blood oxygenation level dependent responses during preparation, and these converged to show inferior prefrontal and related subthalamic nuclei activity in the context of other known changes related to brain attentional networks. Subthalamic nuclei changes were related to the depth of preparatory cardiac deceleration. This pattern of findings suggests that preparation involves the activation of a complex inhibitory neural network implicating brain and autonomic nervous systems.

  17. Sex Differences in How Erotic and Painful Stimuli Impair Inhibitory Control

    Science.gov (United States)

    Yu, Jiaxin; Hung, Daisy L.; Tseng, Philip; Tzeng, Ovid J. L.; Muggleton, Neil G.; Juan, Chi-Hung

    2012-01-01

    Witnessing emotional events such as arousal or pain may impair ongoing cognitive processes such as inhibitory control. We found that this may be true only half of the time. Erotic images and painful video clips were shown to men and women shortly before a stop signal task, which measures cognitive inhibitory control. These stimuli impaired…

  18. A study to evaluate the potential of an in silico approach for predicting dipeptidyl peptidase-IV inhibitory activity in vitro of protein hydrolysates.

    Science.gov (United States)

    Wang, Tzu-Yuan; Hsieh, Cheng-Hong; Hung, Chuan-Chuan; Jao, Chia-Ling; Lin, Pei-Yi; Hsieh, You-Liang; Hsu, Kuo-Chiang

    2017-11-01

    A total of 294 edible protein sequences and 5 commercial proteases listed in the BIOPEP database were analyzed in silico. The frequency (A), a parameter in silico described previously, was examined further to calculating the ratio of truncated peptides with Xaa-proline and/or Xaa-alanine to all peptide fragments in a protein hydrolyzed with a protease, using the BIOPEP database. Then the in vitro DPP-IV inhibitory activity was determined using the same 15 protein and protease combinations to evaluate their relationship. The result shows that A values considering the number of Xaa-proline+Xaa-alanine exhibited a strong correlation with in vitro DPP-IV inhibition rates by Pearson's correlation analysis (r=0.6993; Psilico approach is effective to predict DPP-IV inhibitory activities in vitro of protein hydrolysates. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Inhibitory coherence in a heterogeneous population of subthreshold and suprathreshold type-I neurons

    International Nuclear Information System (INIS)

    Kim, Sang-Yoon; Hong, Duk-Geun; Kim, Jean; Lim, Woochang

    2012-01-01

    We study inhibitory coherence (i.e. collective coherence by synaptic inhibition) in a population of globally coupled type-I neurons, which can fire at arbitrarily low frequency. No inhibitory coherence is observed in a homogeneous population composed of only subthreshold neurons, which exhibit noise-induced firings. In addition to subthreshold neurons, there exist spontaneously firing suprathreshold neurons in a noisy environment of a real brain. To take into consideration the effect of suprathreshold neurons on inhibitory coherence, we consider a heterogeneous population of subthreshold and suprathreshold neurons and investigate the inhibitory coherence by increasing the fraction of suprathreshold neurons P supra . As P supra passes a threshold P* supra , suprathreshold neurons begin to synchronize and play the role of coherent inhibitors for the emergence of inhibitory coherence. Thus, regularly oscillating population-averaged global potential appears for P supra > P* supra . For this coherent case, suprathreshold neurons exhibit sparse spike synchronization (i.e. individual potentials of suprathreshold neurons consist of coherent sparse spikings and coherent subthreshold small-amplitude hoppings). By virtue of their coherent inhibition, sparsely synchronized suprathreshold neurons suppress the noisy activity of subthreshold neurons. Thus, subthreshold neurons exhibit hopping synchronization (i.e. only coherent subthreshold hopping oscillations without spikings appear in the individual potentials of subthreshold neurons). We also characterize the inhibitory coherence in terms of the ‘statistical-mechanical’ spike-based and correlation-based measures, which quantify the average contributions of the microscopic individual spikes and individual potentials to the macroscopic global potential. Finally, the effect of sparse randomness of synaptic connectivity on the inhibitory coherence is briefly discussed. (paper)

  20. Characterization of a translation inhibitory protein from Luffa aegyptiaca.

    Science.gov (United States)

    Ramakrishnan, S; Enghlid, J J; Bryant, H L; Xu, F J

    1989-04-28

    A protein with a molecular weight of about 30,000 was purified from the seeds of Luffa aegyptiaca. This protein inhibited cell free translation at pM concentrations. In spite of functional similarity to other ribosomal inhibitory proteins, the NH2-terminal analysis did not show any significant homology. Competitive inhibition studies indicate no immunological crossreactivity between the inhibitory protein from Luffa aegyptiaca, pokeweed antiviral protein (PAP) and recombinant ricin A chain. Chemical linkage of the protein to a monoclonal antibody reactive to transferrin receptor resulted in a highly cytotoxic conjugate.

  1. Narcissus tazetta lectin shows strong inhibitory effects against ...

    Indian Academy of Sciences (India)

    Prakash

    against human enveloped viruses (Balzarini 2007a). They ... NTL with a high selective index (SI=CC50/IC50 >141) resulting from its potent antiviral activity and low cytotoxicity demonstrates a potential for biotechnological development as an ...

  2. The inhibitory effect of tiamulin on high K(+)-induced contraction in guinea pig intestinal smooth muscle.

    Science.gov (United States)

    Nakajyo, S; Fukui, T; Hara, Y; Shimizu, K; Urakawa, N

    1991-12-01

    Tiamulin with an IC50 of 1.7 x 10(-6) M inhibited both the rapid and sustained contractions induced by hyperosmotically added 60 mM K+ (Hyper 60 K+) without changing the membrane potential in the intestinal muscle. Tiamulin inhibition (2 x 10(-6)-2 x 10(-5) M) of the Ca(2+)-induced contraction in depolarized muscle was competitively antagonized by raising external Ca2+. Tiamulin (2 x 10(-5) M) slightly affected the Hyper 60 K(+)-induced phasic contraction under hypoxia and the carbachol-induced phasic contraction. Moreover, tiamulin (2 x 10(-5) M) inhibited the Hyper 60 K(+)-induced contraction with decreasing [Ca2+]cyt level. Although the inhibitory effect of 10(-7)-10(-5) M monesin, an inhibitor of mitochondrial respiration, on the Hyper 60 K(+)-induced contraction was reduced under hypoxia, the effect of tiamulin (2 x 10(-7)-2 x 10(-4) M) was not modified. Tiamulin changed neither the intracellular Na+ and K+ content of the depolarized muscle nor the Ca(2+)-induced contraction in the chemically skinned preparations. These results suggest that the inhibitory action of tiamulin on the Hyper 60 K(+)-induced tonic contraction is possibly due to the competitive inhibition of Ca2+ entry through the voltage-dependent Ca2+ channel of the intestinal smooth muscle cell.

  3. Comparative synthesis and antimicrobial action of silver nanoparticles and silver nitrate

    International Nuclear Information System (INIS)

    Mosselhy, Dina A.; El-Aziz, Mohamed Abd; Hanna, Magdy; Ahmed, Mohamed A.; Husien, Mona M.; Feng, Qingling

    2015-01-01

    The high wave of antibiotic bacterial resistance has addressed an importance for administration of different antibacterial agents, as silver nanoparticles (Ag NPs). However, many investigators still suffer conflict in the mechanistic antimicrobial action of Ag NPs and Ag + ions. In this regard, our study investigated the comparative antimicrobial action of different sizes of Ag NPs as 8 (nAg1) and 29 (nAg2) nm, in comparison with silver nitrate (AgNO 3 ) against five different bacterial species; Aeromonas hydrophila (A. hydrophila), Pseudomonas putida (Ps. putida), Escherichia coli (E. coli), Staphylococcus aureus (S. aureus), and Bacillus subtilis (B. subtilis) using agar diffusion assay and minimum inhibitory concentration (MIC). The key role of the size of nanomaterials was detected, as the smaller Ag NPs (nAg1) showed more antimicrobial action than the larger particles. Transmission electron microscopy (TEM) studies demonstrated the different mechanistic antibacterial actions of Ag NPs and AgNO 3 . The effect of combining Ag NPs with antibiotics was also investigated. Synergistic effect of combining Ag NPs with ampicillin was detected against S. aureus, in a size-dependent manner as well. To summarize, our results point towards the major role played by the size of Ag NPs in their antimicrobial effects and the different toxic mechanisms of actions induced by Ag NPs and AgNO 3

  4. Comparative synthesis and antimicrobial action of silver nanoparticles and silver nitrate

    Energy Technology Data Exchange (ETDEWEB)

    Mosselhy, Dina A. [Tsinghua University, State Key Laboratory of New Ceramics and Fine Processing, School of Materials Science and Engineering (China); El-Aziz, Mohamed Abd; Hanna, Magdy [Cairo University, Department of Fish Diseases and Management, Faculty of Veterinary Medicine (Egypt); Ahmed, Mohamed A. [Cairo University, Material Science Laboratory (1), Physics Department, Faculty of Science (Egypt); Husien, Mona M. [Animal Health Research Institute, Microbiological Unit, Fish Diseases Department (Egypt); Feng, Qingling, E-mail: biomater@mail.tsinghua.edu.cn [Tsinghua University, State Key Laboratory of New Ceramics and Fine Processing, School of Materials Science and Engineering (China)

    2015-12-15

    The high wave of antibiotic bacterial resistance has addressed an importance for administration of different antibacterial agents, as silver nanoparticles (Ag NPs). However, many investigators still suffer conflict in the mechanistic antimicrobial action of Ag NPs and Ag{sup +} ions. In this regard, our study investigated the comparative antimicrobial action of different sizes of Ag NPs as 8 (nAg1) and 29 (nAg2) nm, in comparison with silver nitrate (AgNO{sub 3}) against five different bacterial species; Aeromonas hydrophila (A. hydrophila), Pseudomonas putida (Ps. putida), Escherichia coli (E. coli), Staphylococcus aureus (S. aureus), and Bacillus subtilis (B. subtilis) using agar diffusion assay and minimum inhibitory concentration (MIC). The key role of the size of nanomaterials was detected, as the smaller Ag NPs (nAg1) showed more antimicrobial action than the larger particles. Transmission electron microscopy (TEM) studies demonstrated the different mechanistic antibacterial actions of Ag NPs and AgNO{sub 3}. The effect of combining Ag NPs with antibiotics was also investigated. Synergistic effect of combining Ag NPs with ampicillin was detected against S. aureus, in a size-dependent manner as well. To summarize, our results point towards the major role played by the size of Ag NPs in their antimicrobial effects and the different toxic mechanisms of actions induced by Ag NPs and AgNO{sub 3}.

  5. Comparative synthesis and antimicrobial action of silver nanoparticles and silver nitrate

    Science.gov (United States)

    Mosselhy, Dina A.; El-Aziz, Mohamed Abd; Hanna, Magdy; Ahmed, Mohamed A.; Husien, Mona M.; Feng, Qingling

    2015-12-01

    The high wave of antibiotic bacterial resistance has addressed an importance for administration of different antibacterial agents, as silver nanoparticles (Ag NPs). However, many investigators still suffer conflict in the mechanistic antimicrobial action of Ag NPs and Ag+ ions. In this regard, our study investigated the comparative antimicrobial action of different sizes of Ag NPs as 8 (nAg1) and 29 (nAg2) nm, in comparison with silver nitrate (AgNO3) against five different bacterial species; Aeromonas hydrophila ( A. hydrophila), Pseudomonas putida ( Ps. putida), Escherichia coli ( E. coli), Staphylococcus aureus ( S. aureus), and Bacillus subtilis ( B. subtilis) using agar diffusion assay and minimum inhibitory concentration (MIC). The key role of the size of nanomaterials was detected, as the smaller Ag NPs (nAg1) showed more antimicrobial action than the larger particles. Transmission electron microscopy (TEM) studies demonstrated the different mechanistic antibacterial actions of Ag NPs and AgNO3. The effect of combining Ag NPs with antibiotics was also investigated. Synergistic effect of combining Ag NPs with ampicillin was detected against S. aureus, in a size-dependent manner as well. To summarize, our results point towards the major role played by the size of Ag NPs in their antimicrobial effects and the different toxic mechanisms of actions induced by Ag NPs and AgNO3.

  6. Kinetic study on coagulase formation and growth of 'Staphylococcus aureus': comparative and combined action of antibiotics and gamma radiation

    International Nuclear Information System (INIS)

    Kiortsis, M.

    1980-01-01

    Coagulase production is preserved in Staphylococcus aureus cultures although growth was strongly reduced after irradiation with 90,000 rads by a 60 Co source. Kinetic studies on the growth and coagulase formation by non-irradiated and irradiated bacteria are reported, using various antibiotics such as chloramphenicol, actinomycin D and mitomycin. Both chloramphenicol (1-50 μg/ml) and actinomycin D (0.05-0.8 μg/ml) added to S. aureus cultures reduce and finally inhibit growth rate and coagulase synthesis proportionally to their concentration in the medium; irradiated and non-irradiated cultures behave similarly to the inhibitory action of those antibiotics. Mitomycin between 0.2-9.6 μg/ml reduces growth, but enzyme production is slightly affected; high levels of coagulase are observed in non-growing cultures. Mitomycin and gamma radiation affecting DNA give similar results: inhibition of growth but not of enzyme formation. Kinetic studies show that coagulase is synthesized during the first five minutes either in irradiated or in non-irradiated cultures. Indication of a de novo synthesis, instead of a mere release of ready-formed enzyme, is given by using chloramphenicol or actinomycin which strongly inhibit coagulase production in irradiated S. aureus. Cultures treated by those antibiotics have their coagulase levels reduced to the same degree, were they irradiated or not; it is assumed that both types of cultures behave similarly, as far as enzyme production is concerned. A massive irradiation dose alone -or mitomycin in high concentrations alone- may suspend bacterial growth although enzyme synthesis continues. A similar result is obtained by combining lower irradiation doses with an appropriate antibiotic. The combined and/or synergistic actions of gamma radiation and antibiotics could successfully differentiate between the two cellular functions: growth and enzyme synthesis [fr

  7. Allosteric Inhibition of Macrophage Migration Inhibitory Factor Revealed by Ibudilast

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Y.; Crichlow, G; Vermeire, J; Leng, L; Du, X; Hodsdon, M; Bucala, R; Cappello, M; Gross, M; et al.

    2010-01-01

    AV411 (ibudilast; 3-isobutyryl-2-isopropylpyrazolo-[1,5-a]pyridine) is an antiinflammatory drug that was initially developed for the treatment of bronchial asthma but which also has been used for cerebrovascular and ocular indications. It is a nonselective inhibitor of various phosphodiesterases (PDEs) and has varied antiinflammatory activity. More recently, AV411 has been studied as a possible therapeutic for the treatment of neuropathic pain and opioid withdrawal through its actions on glial cells. As described herein, the PDE inhibitor AV411 and its PDE-inhibition-compromised analog AV1013 inhibit the catalytic and chemotactic functions of the proinflammatory protein, macrophage migration inhibitory factor (MIF). Enzymatic analysis indicates that these compounds are noncompetitive inhibitors of the p-hydroxyphenylpyruvate (HPP) tautomerase activity of MIF and an allosteric binding site of AV411 and AV1013 is detected by NMR. The allosteric inhibition mechanism is further elucidated by X-ray crystallography based on the MIF/AV1013 binary and MIF/AV1013/HPP ternary complexes. In addition, our antibody experiments directed against MIF receptors indicate that CXCR2 is the major receptor for MIF-mediated chemotaxis of peripheral blood mononuclear cells.

  8. Inhibitory neurotransmission and olfactory memory in honeybees.

    Science.gov (United States)

    El Hassani, Abdessalam Kacimi; Giurfa, Martin; Gauthier, Monique; Armengaud, Catherine

    2008-11-01

    In insects, gamma-aminobutyric acid (GABA) and glutamate mediate fast inhibitory neurotransmission through ligand-gated chloride channel receptors. Both GABA and glutamate have been identified in the olfactory circuit of the honeybee. Here we investigated the role of inhibitory transmission mediated by GABA and glutamate-gated chloride channels (GluCls) in olfactory learning and memory in honeybees. We combined olfactory conditioning with injection of ivermectin, an agonist of GluCl receptors. We also injected a blocker of glutamate transporters (L-trans-PDC) or a GABA analog (TACA). We measured acquisition and retention 1, 24 and 48 h after the last acquisition trial. A low dose of ivermectin (0.01 ng/bee) impaired long-term olfactory memory (48 h) while a higher dose (0.05 ng/bee) had no effect. Double injections of ivermectin and L-trans-PDC or TACA had different effects on memory retention, depending on the doses and agents combined. When the low dose of ivermectin was injected after Ringer, long-term memory was again impaired (48 h). Such an effect was rescued by injection of both TACA and L-trans-PDC. A combination of the higher dose of ivermectin and TACA decreased retention at 48 h. We interpret these results as reflecting the involvement of both GluCl and GABA receptors in the impairment of olfactory long-term memory induced by ivermectin. These results illustrate the diversity of inhibitory transmission and its implication in long-term olfactory memory in honeybees.

  9. Cadmium action in synapses in the brain

    Energy Technology Data Exchange (ETDEWEB)

    Minami, Akira; Takeda, Atsushi; Nishibaba, Daisuke; Tekefuta, Sachiyo; Oku, Naoto [Department of Radiobiochemistry, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka (Japan)

    2001-05-01

    Chronic exposure to cadmium causes central nervous system disorders, e.g., olfactory dysfunction. To clarify cadmium toxicity in synaptic neurotransmission in the brain, the movement and action of cadmium in the synapses was examined using in vivo microdialysis. One and 24 h after injection of {sup 109}CdCl{sub 2} into the amygdala of rats, {sup 109}Cd release into the extracellular space was facilitated by stimulation with high K{sup +}, suggesting that cadmium taken up in amygdalar neurons is released into the synaptic clefts in a calcium- and impulse-dependent manner. To examine the action of cadmium in the synapses, the amygdala was perfused with artificial cerebrospinal fluid containing 10-30 {mu}M CdCl{sub 2}. The release of excitatory neurotransmitters, i.e., glutamate and aspartate, into the extracellular space was decreased during perfusion with cadmium, while the release of inhibitory neurotransmitters, i.e., glycine and {gamma}-amino butyric acid (GABA), into the extracellular space was increased during the period. These results suggest that cadmium released from the amygdalar neuron terminals affects the degree and balance of excitation-inhibition in synaptic neurotransmission. (author)

  10. The Inhibitory Core of the Myostatin Prodomain: Its Interaction with Both Type I and II Membrane Receptors, and Potential to Treat Muscle Atrophy.

    Science.gov (United States)

    Ohsawa, Yutaka; Takayama, Kentaro; Nishimatsu, Shin-ichiro; Okada, Tadashi; Fujino, Masahiro; Fukai, Yuta; Murakami, Tatsufumi; Hagiwara, Hiroki; Itoh, Fumiko; Tsuchida, Kunihiro; Hayashi, Yoshio; Sunada, Yoshihide

    2015-01-01

    Myostatin, a muscle-specific transforming growth factor-β (TGF-β), negatively regulates skeletal muscle mass. The N-terminal prodomain of myostatin noncovalently binds to and suppresses the C-terminal mature domain (ligand) as an inactive circulating complex. However, which region of the myostatin prodomain is required to inhibit the biological activity of myostatin has remained unknown. We identified a 29-amino acid region that inhibited myostatin-induced transcriptional activity by 79% compared with the full-length prodomain. This inhibitory core resides near the N-terminus of the prodomain and includes an α-helix that is evolutionarily conserved among other TGF-β family members, but suppresses activation of myostatin and growth and differentiation factor 11 (GDF11) that share identical membrane receptors. Interestingly, the inhibitory core co-localized and co-immunoprecipitated with not only the ligand, but also its type I and type II membrane receptors. Deletion of the inhibitory core in the full-length prodomain removed all capacity for suppression of myostatin. A synthetic peptide corresponding to the inhibitory core (p29) ameliorates impaired myoblast differentiation induced by myostatin and GDF11, but not activin or TGF-β1. Moreover, intramuscular injection of p29 alleviated muscle atrophy and decreased the absolute force in caveolin 3-deficient limb-girdle muscular dystrophy 1C model mice. The injection suppressed activation of myostatin signaling and restored the decreased numbers of muscle precursor cells caused by caveolin 3 deficiency. Our findings indicate a novel concept for this newly identified inhibitory core of the prodomain of myostatin: that it not only suppresses the ligand, but also prevents two distinct membrane receptors from binding to the ligand. This study provides a strong rationale for the use of p29 in the amelioration of skeletal muscle atrophy in various clinical settings.

  11. Strong deflection lensing by a Lee–Wick black hole

    Directory of Open Access Journals (Sweden)

    Shan-Shan Zhao

    2017-11-01

    Full Text Available We study strong deflection gravitational lensing by a Lee–Wick black hole, which is a non-singular black hole generated by a high derivative modification of Einstein–Hilbert action. The strong deflection lensing is expected to produce a set of relativistic images very closed to the event horizon of the black hole. We estimate its observables for the supermassive black hole in our Galactic center. It is found that the Lee–Wick black hole can be distinguished from the Schwarzschild black hole via such lensing effects when the UV scale is not very large, but the requiring resolution is much higher than current capability.

  12. Anterior Cingulate Cortex Input to the Claustrum Is Required for Top-Down Action Control

    Directory of Open Access Journals (Sweden)

    Michael G. White

    2018-01-01

    Full Text Available Summary: Cognitive abilities, such as volitional attention, operate under top-down, executive frontal cortical control of hierarchically lower structures. The circuit mechanisms underlying this process are unresolved. The claustrum possesses interconnectivity with many cortical areas and, thus, is hypothesized to orchestrate the cortical mantle for top-down control. Whether the claustrum receives top-down input and how this input may be processed by the claustrum have yet to be formally tested, however. We reveal that a rich anterior cingulate cortex (ACC input to the claustrum encodes a preparatory top-down information signal on a five-choice response assay that is necessary for optimal task performance. We further show that ACC input monosynaptically targets claustrum inhibitory interneurons and spiny glutamatergic projection neurons, the latter of which amplify ACC input in a manner that is powerfully constrained by claustrum inhibitory microcircuitry. These results demonstrate ACC input to the claustrum is critical for top-down control guiding action. : White et al. show that anterior cingulate cortex (ACC input to the claustrum encodes a top-down preparatory signal on a 5-choice response assay that is critical for task performance. Claustrum microcircuitry amplifies top-down ACC input in a frequency-dependent manner for eventual propagation to the cortex for cognitive control of action. Keywords: 5CSRTT, optogenetics, fiber photometry, microcircuit, attention, bottom-up, sensory cortices, motor cortices

  13. Characterization of angiotensin-converting enzyme inhibitory activity of fermented milk produced by Lactobacillus helveticus.

    Science.gov (United States)

    Chen, Yongfu; Li, Changkun; Xue, Jiangang; Kwok, Lai-yu; Yang, Jie; Zhang, Heping; Menghe, Bilige

    2015-08-01

    Hypertension affects up to 30% of the adult population in most countries. It is a known risk factor for cardiovascular diseases, including coronary heart disease, peripheral artery disease, and stroke. Owing to the increased health awareness of consumers, the application of angiotensin-converting enzyme (ACE)-inhibitory peptides produced by Lactobacillushelveticus to prevent or control high blood pressure has drawn wide attention. A total of 59 L. helveticus strains were isolated from traditional fermented dairy products and the ACE-inhibitory activity of the fermented milks produced with the isolated microorganisms was assayed. The ACE-inhibitory activity of 38 L. helveticus strains was more than 50%, and 3 strains (IMAU80872, IMAU80852, and IMAU80851) expressing the highest ACE-inhibitory activity were selected for further studies. Particularly, the gastrointestinal protease tolerance and thermostability of the ACE-inhibitory activity in the fermented milks were assessed. Based on these 2 criteria, IMAU80872 was found to be superior over the other 2 strains. Furthermore, IMAU80872 exhibited a high in vitro ACE-inhibitory activity at the following fermentation conditions: fermentation temperature at 40°C, inoculation concentration of 1×10(6) cfu/mL, and fermentation for 18h. Finally, by using ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry analysis, we observed changes of the metabolome along the milk fermentation process of IMAU80872. Furthermore, 6 peptides were identified, which might have ACE-inhibitory activity. In conclusion, we identified a novel ACE-inhibitory L. helveticus strain suitable for the production of fermented milk or other functional dairy products. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  14. Inhibitory control is not lateralized in Parkinson's patients.

    Science.gov (United States)

    Mirabella, G; Fragola, M; Giannini, G; Modugno, N; Lakens, Daniel

    2017-07-28

    Parkinson's disease (PD) is often characterized by asymmetrical symptoms, which are more prominent on the side of the body contralateral to the most extensively affected brain hemisphere. Therefore, lateralized PD presents an opportunity to examine the effects of asymmetric subcortical dopamine deficiencies on cognitive functioning. As it has been hypothesized that inhibitory control relies upon a right-lateralized pathway, we tested whether left-dominant PD (LPD) patients suffered from a more severe deficit in this key executive function than right-dominant PD patients (RPD). To this end, via a countermanding task, we assessed both proactive and reactive inhibition in 20 LPD and 20 RPD patients, and in 20 age-matched healthy subjects. As expected, we found that PD patients were significantly more impaired in both forms of inhibitory control than healthy subjects. However, there were no differences either in reactive or proactive inhibition between LPD and RPD patients. All in all, these data support the idea that brain regions affected by PD play a fundamental role in subserving inhibitory function, but do not sustain the hypothesis according to which this executive function is predominantly or solely computed by the brain regions of the right hemisphere. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Dynamics of excitatory and inhibitory networks are differentially altered by selective attention

    Science.gov (United States)

    Snyder, Adam C.; Morais, Michael J.

    2016-01-01

    Inhibition and excitation form two fundamental modes of neuronal interaction, yet we understand relatively little about their distinct roles in service of perceptual and cognitive processes. We developed a multidimensional waveform analysis to identify fast-spiking (putative inhibitory) and regular-spiking (putative excitatory) neurons in vivo and used this method to analyze how attention affects these two cell classes in visual area V4 of the extrastriate cortex of rhesus macaques. We found that putative inhibitory neurons had both greater increases in firing rate and decreases in correlated variability with attention compared with putative excitatory neurons. Moreover, the time course of attention effects for putative inhibitory neurons more closely tracked the temporal statistics of target probability in our task. Finally, the session-to-session variability in a behavioral measure of attention covaried with the magnitude of this effect. Together, these results suggest that selective targeting of inhibitory neurons and networks is a critical mechanism for attentional modulation. PMID:27466133

  16. Dynamics of excitatory and inhibitory networks are differentially altered by selective attention.

    Science.gov (United States)

    Snyder, Adam C; Morais, Michael J; Smith, Matthew A

    2016-10-01

    Inhibition and excitation form two fundamental modes of neuronal interaction, yet we understand relatively little about their distinct roles in service of perceptual and cognitive processes. We developed a multidimensional waveform analysis to identify fast-spiking (putative inhibitory) and regular-spiking (putative excitatory) neurons in vivo and used this method to analyze how attention affects these two cell classes in visual area V4 of the extrastriate cortex of rhesus macaques. We found that putative inhibitory neurons had both greater increases in firing rate and decreases in correlated variability with attention compared with putative excitatory neurons. Moreover, the time course of attention effects for putative inhibitory neurons more closely tracked the temporal statistics of target probability in our task. Finally, the session-to-session variability in a behavioral measure of attention covaried with the magnitude of this effect. Together, these results suggest that selective targeting of inhibitory neurons and networks is a critical mechanism for attentional modulation. Copyright © 2016 the American Physiological Society.

  17. Communicating actionable risk for terrorism and other hazards.

    Science.gov (United States)

    Wood, Michele M; Mileti, Dennis S; Kano, Megumi; Kelley, Melissa M; Regan, Rotrease; Bourque, Linda B

    2012-04-01

    We propose a shift in emphasis when communicating to people when the objective is to motivate household disaster preparedness actions. This shift is to emphasize the communication of preparedness actions (what to do about risk) rather than risk itself. We have called this perspective "communicating actionable risk," and it is grounded in diffusion of innovations and communication theories. A representative sample of households in the nation was analyzed using a path analytic framework. Preparedness information variables (including content, density, and observation), preparedness mediating variables (knowledge, perceived effectiveness, and milling), and preparedness actions taken were modeled. Clear results emerged that provide a strong basis for communicating actionable risk, and for the conclusion both that information observed (seeing preparedness actions that other have taken) and information received (receiving recommendations about what preparedness actions to take) play key, although different, roles in motivating preparedness actions among the people in our nation. © 2011 Society for Risk Analysis.

  18. Inhibitory effect of burdock leaves on elastase and tyrosinase activity

    Science.gov (United States)

    Horng, Chi-Ting; Wu, Hsing-Chen; Chiang, Ni-Na; Lee, Chiu-Fang; Huang, Yu-Syuan; Wang, Hui-Yun; Yang, Jai-Sing; Chen, Fu-An

    2017-01-01

    Burdock (Arctium lappa L.) leaves generate a considerable amount of waste following burdock root harvest in Taiwan. To increase the use of burdock leaves, the present study investigated the optimal methods for producing burdock leaf extract (BLE) with high antioxidant polyphenolic content, including drying methods and solvent extraction concentration. In addition, the elastase and tyrosinase inhibitory activity of BLE was examined. Burdock leaves were dried by four methods: Shadow drying, oven drying, sun drying and freeze-drying. The extract solution was then subjected to total polyphenol content analysis and the method that produced BLE with the highest amount of total antioxidant components was taken forward for further analysis. The 1,1-diphenyl-2-pycrylhydrazyl scavenging, antielastase and antityrosinase activity of the BLE were measured to enable the evaluation of the antioxidant and skin aging-associated enzyme inhibitory activities of BLE. The results indicated that the total polyphenolic content following extraction with ethanol (EtOH) was highest using the freeze-drying method, followed by the oven drying, shadow drying and sun drying methods. BLE yielded a higher polyphenol content and stronger antioxidant activity as the ratio of the aqueous content of the extraction solvent used increased. BLE possesses marked tyrosinase and elastase inhibitory activities, with its antielastase activity notably stronger compared with its antityrosinase activity. These results indicate that the concentration of the extraction solvent was associated with the antioxidant and skin aging-associated enzyme inhibitory activity of BLE. The reactive oxygen species scavenging theory of skin aging may explain the tyrosinase and elastase inhibitory activity of BLE. In conclusion, the optimal method for obtaining BLE with a high antioxidant polyphenolic content was freeze-drying followed by 30–50% EtOH extraction. In addition, the antielastase and antityrosinase activities of the

  19. Inhibitory effects of Bacillus subtilis on plant pathogens of conservatory in high latitudes

    Science.gov (United States)

    Xue, Chun-Mei; Wang, Xue; Yang, Jia-Li; Zhang, Yue-Hua

    2018-03-01

    Researching the effect of three kinds of Bacillus and their mixed strains inhibitory on common fungal diseases of conservatory vegetables. The results showed that B. megaterium culture medium had a significant inhibition effect on Cucumber Fusarium wilt, and the inhibition rate was up to 84.36%; B. mucilaginosus and B. megaterium sterile superna-tant had an obvious inhibitory effect on brown disease of eggplant, and the inhibition rate as high as 85.49%; B. subtilis sterile supernatant had a good inhibitory effect on the spore germination of C. Fusarium wilt, and the inhibition rate was 76.83%. The results revealed that Bacillus had a significant inhibitory effect on five common fungal pathogens. Three kinds of Bacillus can be used for the prevention and control of common fungal diseases in conservatory vegetables.

  20. Structures, chemotaxonomic significance, cytotoxic and Na(+),K(+)-ATPase inhibitory activities of new cardenolides from Asclepias curassavica.

    Science.gov (United States)

    Zhang, Rong-Rong; Tian, Hai-Yan; Tan, Ya-Fang; Chung, Tse-Yu; Sun, Xiao-Hui; Xia, Xue; Ye, Wen-Cai; Middleton, David A; Fedosova, Natalya; Esmann, Mikael; Tzen, Jason T C; Jiang, Ren-Wang

    2014-11-28

    Five new cardenolide lactates (1–5) and one new dioxane double linked cardenolide glycoside (17) along with 15 known compounds (6–16 and 18–21) were isolated from the ornamental milkweed Asclepias curassavica. Their structures were elucidated by extensive spectroscopic methods (IR, UV, MS, 1D- and 2D-NMR). The molecular structures and absolute configurations of 1–3 and 17 were further confirmed by single-crystal X-ray diffraction analysis. Simultaneous isolation of dioxane double linked cardenolide glycosides (17–21) and cardenolide lactates (1–5) provided unique chemotaxonomic markers for this genus. Compounds 1–21 were evaluated for the inhibitory activities against DU145 prostate cancer cells. The dioxane double linked cardenolide glycosides showed the most potent cytotoxic effect followed by normal cardenolides and cardenolide lactates, while the C21 steroids were non-cytotoxic. Enzymatic assay established a correlation between the cytotoxic effects in DU145 cancer cells and the Ki for the inhibition of Na(+),K(+)-ATPase. Molecular docking analysis revealed relatively strong H-bond interactions between the bottom of the binding cavity and compounds 18 or 20, and explained why the dioxane double linked cardenolide glycosides possessed higher inhibitory potency on Na(+),K(+)-ATPase than the cardenolide lactate.

  1. Quantifying the importance of MSP1-19 as a target of growth-inhibitory and protective antibodies against Plasmodium falciparum in humans.

    Directory of Open Access Journals (Sweden)

    Danny W Wilson

    Full Text Available BACKGROUND: Antibodies targeting blood stage antigens are important in protection against malaria, but the key targets and mechanisms of immunity are not well understood. Merozoite surface protein 1 (MSP1 is an abundant and essential protein. The C-terminal 19 kDa region (MSP1-19 is regarded as a promising vaccine candidate and may also be an important target of immunity. METHODOLOGY/FINDINGS: Growth inhibitory antibodies against asexual-stage parasites and IgG to recombinant MSP1-19 were measured in plasma samples from a longitudinal cohort of 206 children in Papua New Guinea. Differential inhibition by samples of mutant P. falciparum lines that expressed either the P. falciparum or P. chabaudi form of MSP1-19 were used to quantify MSP1-19 specific growth-inhibitory antibodies. The great majority of children had detectable IgG to MSP1-19, and high levels of IgG were significantly associated with a reduced risk of symptomatic P. falciparum malaria during the 6-month follow-up period. However, there was little evidence of PfMSP1-19 specific growth inhibition by plasma samples from children. Similar results were found when testing non-dialysed or dialysed plasma, or purified antibodies, or when measuring growth inhibition in flow cytometry or microscopy-based assays. Rabbit antisera generated by immunization with recombinant MSP1-19 demonstrated strong MSP1-19 specific growth-inhibitory activity, which appeared to be due to much higher antibody levels than human samples; antibody avidity was similar between rabbit antisera and human plasma. CONCLUSIONS/SIGNIFICANCE: These data suggest that MSP1-19 is not a major target of growth inhibitory antibodies and that the protective effects of antibodies to MSP1-19 are not due to growth inhibitory activity, but may instead be mediated by other mechanisms. Alternatively, antibodies to MSP1-19 may act as a marker of protective immunity.

  2. Macrophage migration inhibitory factor is associated with aneurysmal expansion

    DEFF Research Database (Denmark)

    Pan, Jie-Hong; Lindholt, Jes Sanddal; Sukhova, Galina K

    2003-01-01

    Macrophage migration inhibitory factor (MIF) is an inflammatory cytokine released mainly from macrophages and activated lymphocytes. Both atherosclerosis and abdominal aortic aneurysm (AAA) are inflammatory diseases tightly linked to the function of these cells. The correlation and contribution o...... of MIF to these human diseases remain unknown, although a recent rabbit study showed expression of this cytokine in atherosclerotic lesions.......Macrophage migration inhibitory factor (MIF) is an inflammatory cytokine released mainly from macrophages and activated lymphocytes. Both atherosclerosis and abdominal aortic aneurysm (AAA) are inflammatory diseases tightly linked to the function of these cells. The correlation and contribution...

  3. Antioxidant and protease-inhibitory potential of extracts from grains of oat

    Directory of Open Access Journals (Sweden)

    Krošlák Erik

    2016-01-01

    Full Text Available The most of important crops cultivated for production of foods and feeds could be considered as plants possessing nutraceutical or medically interesting compounds, especially if can be eaten without processing. Chemical and biological parameters that were evaluated in 100 oat (Avena sativa L. genotypes were others than those that are important in food and feed production. Contents of polyphenols and flavonoids, radical scavenging activity (DPPH, and inhibitory activities against five proteases (trypsin, thrombin, urokinase, elastase, cathepsin B were analyzed in extracts from mature grains. The antioxidant activity (DPPH correlated to the content of total polyphenols. Only a minority (15 from 100 of analyzed genotypes created separate subgroup with a high content of polyphenols, flavonoids, and high antioxidant activity. The best in these parameters were genotypes CDC-SOL-FI, Saul, and Avesta, respectively. Fifteen other genotypes assembled another minority subgroup (also 15 from 100 on the basis of their high inhibitory activities against tested proteases. The highest trypsin-, urokinase-, and elastase-inhibitory activities were in genotype Racoon, the best in thrombin-, and cathepsin B-inhibitory activities were genotypes Expression and SW Kerstin, respectively. Three oats genotypes – Rhea, AC Percy, and Detvan appeared in both subgroups.

  4. Patterned sensory nerve stimulation enhances the reactivity of spinal Ia inhibitory interneurons.

    Science.gov (United States)

    Kubota, Shinji; Hirano, Masato; Morishita, Takuya; Uehara, Kazumasa; Funase, Kozo

    2015-03-25

    Patterned sensory nerve stimulation has been shown to induce plastic changes in the reciprocal Ia inhibitory circuit. However, the mechanisms underlying these changes have not yet been elucidated in detail. The aim of the present study was to determine whether the reactivity of Ia inhibitory interneurons could be altered by patterned sensory nerve stimulation. The degree of reciprocal Ia inhibition, the conditioning effects of transcranial magnetic stimulation (TMS) on the soleus (SOL) muscle H-reflex, and the ratio of the maximum H-reflex amplitude versus maximum M-wave (H(max)/M(max)) were examined in 10 healthy individuals. Patterned electrical nerve stimulation was applied to the common peroneal nerve every 1 s (100 Hz-5 train) at the motor threshold intensity of tibialis anterior muscle to induce activity changes in the reciprocal Ia inhibitory circuit. Reciprocal Ia inhibition, the TMS-conditioned H-reflex amplitude, and H(max)/M(max) were recorded before, immediately after, and 15 min after the electrical stimulation. The patterned electrical nerve stimulation significantly increased the degree of reciprocal Ia inhibition and decreased the amplitude of the TMS-conditioned H-reflex in the short-latency inhibition phase, which was presumably mediated by Ia inhibitory interneurons. However, it had no effect on H(max)/M(max). Our results indicated that patterned sensory nerve stimulation could modulate the activity of Ia inhibitory interneurons, and this change may have been caused by the synaptic modification of Ia inhibitory interneuron terminals. These results may lead to a clearer understanding of the spinal cord synaptic plasticity produced by repetitive sensory inputs. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.

  5. Identification of octanal as plant growth inhibitory volatile compound released from Heracleum sosnowskyi fruit.

    Science.gov (United States)

    Mishyna, Maryia; Laman, Nikolai; Prokhorov, Valery; Maninang, John Solomon; Fujii, Yoshiharu

    2015-05-01

    Heracleum sosnowskyi Manden of the Apiaceae family is a malignant invasive plant in Eastern Europe, Belarus and Russia. The species is known for its prolific seed production, which has been linked to the plant's invasive success. The fruit also has a strong aroma, but the contribution of the fruit's volatile constituent to out-compete neighboring plants has not been fully established. In this study, fruit volatiles of H. sosnowskyi and conspecifics (i.e. H. asperum, H. lescovii, H. dissectum, H. hirtum) were identified by headspace gas chromatography-mass spectrometry (HS-GC-MS). Octyl acetate, octanol, octanal, hexyl isobutyrate, and hexyl-2-methyl butyrate were found to be the principal volatiles. Using authentic standards, the growth-inhibitory property of the individual compounds was assayed by the novel Cotton swab method. Assay results with lettuce (Lactuca sativa) showed that octanal strongly inhibited seed germination and radicle elongation of seedlings. The results suggest that octanal may be the main contributor to the allelopathic activity of H. sosnowksyi fruits. Furthermore, the mixture of fruit volatiles from the invasive H. sosnowskyi more strongly delayed lettuce seedling elongation than the volatiles from fruits of the non-invasive H. asperum, H. lescovii, H. dissectum and H. hirtum. Thus, the present study is the first to demonstrate the possible involvement of fruit volatiles of Heracleum species in plant-plant interaction.

  6. PTP1B, α-glucosidase, and DPP-IV inhibitory effects for chromene derivatives from the leaves of Smilax china L.

    Science.gov (United States)

    Zhao, Bing Tian; Le, Duc Dat; Nguyen, Phi Hung; Ali, Md Yousof; Choi, Jae-Sue; Min, Byung Sun; Shin, Heung Mook; Rhee, Hae Ik; Woo, Mi Hee

    2016-06-25

    Two new flavonoids, bismilachinone (11) and smilachinin (14), were isolated from the leaves of Smilax china L. together with 14 known compounds. Their structures were elucidated using spectroscopic methods. The PTP1B, α-glucosidase, and DPP-IV inhibitory activities of compounds 1-16 were evaluated at the molecular level. Among them, compounds 4, 7, and 10 showed moderate DPP-IV inhibitory activities with IC50 values of 20.81, 33.12, and 32.93 μM, respectively. Compounds 3, 4, 6, 11, 12, and 16 showed strong PTP1B inhibitory activities, with respective IC50 values of 7.62, 10.80, 0.92, 2.68, 9.77, and 24.17 μM compared with the IC50 value for the positive control (ursolic acid: IC50 = 1.21 μM). Compounds 2-7, 11, 12, 15, and 16 showed potent α-glucosidase inhibitory activities, with respective IC50 values of 8.70, 81.66, 35.11, 35.92, 7.99, 26.28, 11.28, 62.68, 44.32, and 70.12 μM. The positive control, acarbose, displayed an IC50 value of 175.84 μM. In the kinetic study for the PTP1B enzyme, compounds 6, 11, and 12 displayed competitive inhibition with Ki values of 3.20, 8.56, and 5.86 μM, respectively. Compounds 3, 4, and 16 showed noncompetitive inhibition with Ki values of 18.75, 5.95, and 22.86 μM, respectively. Molecular docking study for the competitive inhibitors (6, 11, and 12) radically corroborates the binding affinities and inhibition of PTP1B enzymes. These results indicated that the leaves of Smilax china L. may contain compounds with anti-diabetic activity. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  7. The role of cardiac vagal tone and inhibitory control in pre-schoolers' listening comprehension.

    Science.gov (United States)

    Scrimin, Sara; Patron, Elisabetta; Florit, Elena; Palomba, Daniela; Mason, Lucia

    2017-12-01

    This study investigated the role of basal cardiac activity and inhibitory control at the beginning of the school year in predicting oral comprehension at the end of the year in pre-schoolers. Forty-three, 4-year-olds participated in the study. At the beginning of the school year children's electrocardiogram at rest was registered followed by the assessment of inhibitory control as well as verbal working memory and verbal ability. At the end of the year all children were administered a listening comprehension ability measure. A stepwise regression showed a significant effect of basal cardiac vagal tone in predicting listening comprehension together with inhibitory control and verbal ability. These results are among the first to show the predictive role of basal cardiac vagal tone and inhibitory control in pre-schoolers' oral text comprehension, and offer new insight into the association between autonomic regulation of the heart, inhibitory control, and cognitive activity at a young age. © 2017 Wiley Periodicals, Inc.

  8. Lipase inhibitory activity of Carica papaya, Chrysophyllum cainito, Corcorus olitorius, Cympogon citrates and Syzygium cumini extracts

    Directory of Open Access Journals (Sweden)

    Briones, A.T.

    2017-09-01

    Full Text Available The lipase inhibitory action of Carica papaya, Chrysophyllum cainito, Corcorus olitorius, Cymbopogon citrates and Syzygium cumini were evaluated to explore for the presence of anti-obesity compounds and their potential weight-lowering activity. Enzyme inhibition results of the alcoholic extracts of the five plants showed that C. cainito has the highest percent inhibition at 74.91% while S. cumini, C. citratus, C. olitorius and C. papaya obtained less than 50% average inhibition. C. cainito was partitioned using hexane and ethyl acetate to further concentrate the bioactive compounds. The lipase inhibition assay of hexane and ethyl acetate extracts showed 92.11% inhibition and 21.9% inhibition, respectively. The greater activity in the former may imply that majority of potential anti-lipase constituents are found in the hexane portion.

  9. Antioxidant and ACE Inhibitory Bioactive Peptides Purified from Egg Yolk Proteins

    Directory of Open Access Journals (Sweden)

    Marwa Yousr

    2015-12-01

    Full Text Available Protein by-products from the extraction of lecithin from egg yolk can be converted into value-added products, such as bioactive hydrolysates and peptides that have potential health enhancing antioxidant, and antihypertensive properties. In this study, the antioxidant and angiotensin converting enzyme (ACE inhibitory activities of peptides isolated and purified from egg yolk protein were investigated. Defatted egg yolk was hydrolyzed using pepsin and pancreatin and sequentially fractionated by ultrafiltration, followed by gel filtration to produce egg yolk gel filtration fractions (EYGF. Of these, two fractions, EYGF-23 and EYGF-33, effectively inhibited the peroxides and thiobarbituric acid reactive substance (TBARS in an oxidizing linoleic acid model system. The antioxidant mechanism involved superoxide anion and hydroxyl radicals scavenging and ferrous chelation. The presence of hydrophobic amino acids such as tyrosine (Y and tryptophan (W, in sequences identified by LC-MS as WYGPD (EYGF-23 and KLSDW (EYGF-33, contributed to the antioxidant activity and were not significantly different from the synthetic BHA antioxidant. A third fraction (EYGF-56 was also purified from egg yolk protein by gel filtration and exhibited high ACE inhibitory activity (69% and IC50 value (3.35 mg/mL. The SDNRNQGY peptide (10 mg/mL had ACE inhibitory activity, which was not significantly different from that of the positive control captopril (0.5 mg/mL. In addition, YPSPV in (EYGF-33 (10 mg/mL had higher ACE inhibitory activity compared with captopril. These findings indicated a substantial potential for producing valuable peptides with antioxidant and ACE inhibitory activity from egg yolk.

  10. Antioxidant and ACE Inhibitory Bioactive Peptides Purified from Egg Yolk Proteins.

    Science.gov (United States)

    Yousr, Marwa; Howell, Nazlin

    2015-12-07

    Protein by-products from the extraction of lecithin from egg yolk can be converted into value-added products, such as bioactive hydrolysates and peptides that have potential health enhancing antioxidant, and antihypertensive properties. In this study, the antioxidant and angiotensin converting enzyme (ACE) inhibitory activities of peptides isolated and purified from egg yolk protein were investigated. Defatted egg yolk was hydrolyzed using pepsin and pancreatin and sequentially fractionated by ultrafiltration, followed by gel filtration to produce egg yolk gel filtration fractions (EYGF). Of these, two fractions, EYGF-23 and EYGF-33, effectively inhibited the peroxides and thiobarbituric acid reactive substance (TBARS) in an oxidizing linoleic acid model system. The antioxidant mechanism involved superoxide anion and hydroxyl radicals scavenging and ferrous chelation. The presence of hydrophobic amino acids such as tyrosine (Y) and tryptophan (W), in sequences identified by LC-MS as WYGPD (EYGF-23) and KLSDW (EYGF-33), contributed to the antioxidant activity and were not significantly different from the synthetic BHA antioxidant. A third fraction (EYGF-56) was also purified from egg yolk protein by gel filtration and exhibited high ACE inhibitory activity (69%) and IC50 value (3.35 mg/mL). The SDNRNQGY peptide (10 mg/mL) had ACE inhibitory activity, which was not significantly different from that of the positive control captopril (0.5 mg/mL). In addition, YPSPV in (EYGF-33) (10 mg/mL) had higher ACE inhibitory activity compared with captopril. These findings indicated a substantial potential for producing valuable peptides with antioxidant and ACE inhibitory activity from egg yolk.

  11. New polyacetylenes glycoside from Eclipta prostrate with DGAT inhibitory activity.

    Science.gov (United States)

    Meng, Xiao; Li, Ban-Ban; Lin, Xin; Jiang, Yi-Yu; Zhang, Le; Li, Hao-Ze; Cui, Long

    2018-06-08

    One new polyacetylene glycoside eprostrata Ⅰ (1), together with seven known compounds (2-8), were isolated from Eclipta prostrata. Their structures were elucidated on the basis of spectroscopic and physico-chemical analyses. All the isolates were evaluated inhibitory activity on DGAT in an in vitro assay. Compounds 1-8 were found to exhibit inhibitory activity of DGAT1 with IC 50 values ranging from 74.4 ± 1.3 to 101.1 ± 1.1 μM.

  12. Inhibitory effect of mTOR activator MHY1485 on autophagy: suppression of lysosomal fusion.

    Directory of Open Access Journals (Sweden)

    Yeon Ja Choi

    Full Text Available Autophagy is a major degradative process responsible for the disposal of cytoplasmic proteins and dysfunctional organelles via the lysosomal pathway. During the autophagic process, cells form double-membraned vesicles called autophagosomes that sequester disposable materials in the cytoplasm and finally fuse with lysosomes. In the present study, we investigated the inhibition of autophagy by a synthesized compound, MHY1485, in a culture system by using Ac2F rat hepatocytes. Autophagic flux was measured to evaluate the autophagic activity. Autophagosomes were visualized in Ac2F cells transfected with AdGFP-LC3 by live-cell confocal microscopy. In addition, activity of mTOR, a major regulatory protein of autophagy, was assessed by western blot and docking simulation using AutoDock 4.2. In the result, treatment with MHY1485 suppressed the basal autophagic flux, and this inhibitory effect was clearly confirmed in cells under starvation, a strong physiological inducer of autophagy. The levels of p62 and beclin-1 did not show significant change after treatment with MHY1485. Decreased co-localization of autophagosomes and lysosomes in confocal microscopic images revealed the inhibitory effect of MHY1485 on lysosomal fusion during starvation-induced autophagy. These effects of MHY1485 led to the accumulation of LC3II and enlargement of the autophagosomes in a dose- and time-dependent manner. Furthermore, MHY1485 induced mTOR activation and correspondingly showed a higher docking score than PP242, a well-known ATP-competitive mTOR inhibitor, in docking simulation. In conclusion, MHY1485 has an inhibitory effect on the autophagic process by inhibition of fusion between autophagosomes and lysosomes leading to the accumulation of LC3II protein and enlarged autophagosomes. MHY1485 also induces mTOR activity, providing a possibility for another regulatory mechanism of autophagy by the MHY compound. The significance of this study is the finding of a novel

  13. Short-Term Pretreatment of Sub-Inhibitory Concentrations of Gentamycin Inhibits the Swarming Motility of Escherichia Coli by Down-Regulating the Succinate Dehydrogenase Gene

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    Yijing Zhuang

    2016-09-01

    Full Text Available Background/Aims: Motility is a feature of many pathogens that contributes to the migration and dispersion of the infectious agent. Whether gentamycin has a post-antibiotic effect (PAE on the swarming and swimming motility of Escherichia coli (E. coli remains unknown. In this study, we aimed to examine whether short-term pretreatment of sub-inhibitory concentrations of gentamycin alter motility of E. coli and the mechanisms involved therein. Methods: After exposure to sub-inhibitory concentrations (0.8 μg/ml of gentamicin, the swarming and swimming motility of E. coli was tested in semi-solid media. Real-time PCR was used to detect the gene expression of succinate dehydrogenase (SDH. The production of SDH and fumarate by E. coli pretreated with or without gentamycin was measured. Fumarate was added to swarming agar to determine whether fumarate could restore the swarming motility of E. coli. Results: After pretreatment of E. coli with sub-inhibitory concentrations of gentamycin, swarming motility was repressed in the absence of growth inhibition. The expression of all four subunits of SDH was down-regulated, and the intracellular concentration of SDH and fumarate, produced by E. coli, were both decreased. Supplementary fumarate could restore the swarming motility inhibited by gentamycin. A selective inhibitor of SDH (propanedioic acid could strongly repress the swarming motility. Conclusion: Sub-inhibitory concentrations of gentamycin inhibits the swarming motility of E. coli. This effect is mediated by a reduction in cellular fumarate caused by down-regulation of SDH. Gentamycin may be advantageous for treatment of E. coli infections.

  14. Antibacterial Mode of Action of the Essential Oil Obtained from Chamaecyparis obtusa Sawdust on the Membrane Integrity of Selected Foodborne Pathogens

    Directory of Open Access Journals (Sweden)

    Vivek K. Bajpai

    2014-01-01

    Full Text Available The present study examines the possible antibacterial mechanism of action of the essential oil obtained from Chamaecyparis obtusa (COEO sawdust against foodborne pathogenic bacteria. The COEO was obtained by microwave-assisted hydrodistillation of C. obtusa sawdust. The minimum inhibitory concentration (MIC and minimum bactericidal concentration (MBC values of COEO against the tested foodborne pathogens including Bacillus cereus ATCC 13061, Listeria monocytogenes ATCC 7644, Staphylococcus aureus ATCC 12600, Salmonella Typhimurium ATCC 43174 and Escherichia coli ATCC 43889 were found in the range from 62.5 to 500 μg/mL and from 125 to 1000 μg/mL, respectively. At the MIC concentrations, the COEO had potential inhibitory effect on the cell viability of the tested bacteria. In addition, the scanning electron microscopic analysis confirmed the inhibitory effect of COEO by revealing significant morphological alterations or rupture of the cell membranes of B. cereus ATCC 13061 and E. coli ATCC 43889. Moreover, the mode of action of COEO on the cell membrane of both Gram-positive B. cereus ATCC 13061 and Gram-negative E. coli ATCC 43889 bacteria was confirmed by marked release of extracellular adenosine 5’-triphosphate (ATP and cellular material that absorbs at 260 nm, and by efflux of potassium ions. These findings suggest that COEO holds a broad-spectrum antibacterial efficacy, confirming its influence on the membrane integrity and morphological characteristics of tested foodborne pathogens.

  15. Inhibitory control and negative emotional processing in psychopathy and antisocial personality disorder.

    Science.gov (United States)

    Verona, Edelyn; Sprague, Jenessa; Sadeh, Naomi

    2012-05-01

    The field of personality disorders has had a long-standing interest in understanding interactions between emotion and inhibitory control, as well as neurophysiological indices of these processes. More work in particular is needed to clarify differential deficits in offenders with antisocial personality disorder (APD) who differ on psychopathic traits, as APD and psychopathy are considered separate, albeit related, syndromes. Evidence of distinct neurobiological processing in these disorders would have implications for etiology-based personality disorder taxonomies in future psychiatric classification systems. To inform this area of research, we recorded event-related brain potentials during an emotional-linguistic Go/No-Go task to examine modulation of negative emotional processing by inhibitory control in three groups: psychopathy (n = 14), APD (n = 16), and control (n = 15). In control offenders, inhibitory control demands (No-Go vs. Go) modulated frontal-P3 amplitude to negative emotional words, indicating appropriate prioritization of inhibition over emotional processing. In contrast, the psychopathic group showed blunted processing of negative emotional words regardless of inhibitory control demands, consistent with research on emotional deficits in psychopathy. Finally, the APD group demonstrated enhanced processing of negative emotion words in both Go and No-Go trials, suggesting a failure to modulate negative emotional processing when inhibitory control is required. Implications for emotion-cognition interactions and putative etiological processes in these personality disorders are discussed.

  16. Growth inhibitory alkaloids from mesquite (Prosopis juliflora (Sw.) DC.) leaves.

    Science.gov (United States)

    Nakano, Hiroshi; Nakajima, Eri; Hiradate, Syuntaro; Fujii, Yoshiharu; Yamada, Kosumi; Shigemori, Hideyuki; Hasegawa, Koji

    2004-03-01

    Plant growth inhibitory alkaloids were isolated from the extract of mesquite [Prosopis juliflora (Sw.) DC.] leaves. Their chemical structures were established by ESI-MS, 1H and 13C NMR spectra analysis. The I50 value (concentration required for 50% inhibition of control) for root growth of cress (Lepidium sativum L.) seedlings was 400 microM for 3''''-oxo-juliprosopine, 500 microM for secojuliprosopinal, and 100 microM for a (1:1) mixture of 3-oxo-juliprosine and 3'-oxo-juliprosine, respectively. On the other hand, the minimum concentration exhibiting inhibitory effect on shoot growth of cress seedlings was 10 microM for 3''''-oxo-juliprosopine, 100 microM for secojuliprosopinal, and 1 microM for a (1:1) mixture of 3-oxo-juliprosine and 3'-oxo-juliprosine, respectively. Among these compounds, a (1:1) mixture of 3-oxo-juliprosine and 3'-oxo-juliprosine exhibited the strongest inhibitory effect on the growth of cress seedlings.

  17. Inhibitory assay for degradation of collagen IV by cathepsin B with a surface plasmon resonance sensor.

    Science.gov (United States)

    Shoji, Atsushi; Suenaga, Yumiko; Hosaka, Atsushi; Ishida, Yuuki; Yanagida, Akio; Sugawara, Masao

    2017-10-25

    We describe a simple method for evaluating the inhibition of collagen IV degradation by cathepsin B with a surface plasmon resonance (SPR) biosensor. The change in the SPR signal decreased with an increase in the concentration of cathepsin B inhibitors. The order of the inhibitory constant (Ki) obtained by the SPR method was CA074Me≈Z-Phe-Phe-FMK < leupeptin. This order was different from that obtained by benzyloxycarbonyl-Phe-Phe-Fluoromethylketone (Z-Phe-Phe-FMK) as a peptide substrate. The comparison of Ki suggested that CA074 and Z-Phe-Phe-FMK inhibited exopeptidase activity, and leupeptin inhibited the endopeptidase activity of cathepsin B more strongly. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Sustaining Collective Action in Urbanizing China

    DEFF Research Database (Denmark)

    Kuang, Xianwen; Goebel, Christian

    2013-01-01

    The recent years have seen a proliferation of scholarship on protests and other forms of collective action in China. Important insights have been gained into how conflicts between social groups and local governments begin, which strategies and instruments protesters apply, and under which...... challenges of sustaining collective action in China: the continuing existence of substantial grievances, the re-activation of strong social ties, the presence of unifying frames and an adaptive protest leadership. The comparison shows that especially the last factor is crucial: while the two villages were...... similar in all other respects, leadership in Village B was far more adaptive in Village A, which goes a long way towards explaining why collective action could be sustained twice as long in Village B....

  19. The gonadotropin-inhibitory hormone (Lpxrfa) system's regulation of reproduction in the brain-pituitary axis of the zebrafish (Danio rerio).

    Science.gov (United States)

    Spicer, Olivia Smith; Zmora, Nilli; Wong, Ten-Tsao; Golan, Matan; Levavi-Sivan, Berta; Gothilf, Yoav; Zohar, Yonathan

    2017-05-01

    Gonadotropin-inhibitory hormone (GNIH) was discovered in quail with the ability to reduce gonadotropin expression/secretion in the pituitary. There have been few studies on GNIH orthologs in teleosts (LPXRFamide (Lpxrfa) peptides), which have provided inconsistent results. Therefore, the goal of this study was to determine the roles and modes of action by which Lpxrfa exerts its functions in the brain-pituitary axis of zebrafish (Danio rerio). We localized Lpxrfa soma to the ventral hypothalamus, with fibers extending throughout the brain and to the pituitary. In the preoptic area, Lpxrfa fibers interact with gonadotropin-releasing hormone 3 (Gnrh3) soma. In pituitary explants, zebrafish peptide Lpxrfa-3 downregulated luteinizing hormone beta subunit and common alpha subunit expression. In addition, Lpxrfa-3 reduced gnrh3 expression in brain slices, offering another pathway for Lpxrfa to exert its effects on reproduction. Receptor activation studies, in a heterologous cell-based system, revealed that all three zebrafish Lpxrfa peptides activate Lpxrf-R2 and Lpxrf-R3 via the PKA/cAMP pathway. Receptor activation studies demonstrated that, in addition to activating Lpxrf receptors, zebrafish Lpxrfa-2 and Lpxrfa-3 antagonize Kisspeptin-2 (Kiss2) activation of Kisspeptin receptor-1a (Kiss1ra). The fact that kiss1ra-expressing neurons in the preoptic area are innervated by Lpxrfa-ir fibers suggests an additional pathway for Lpxrfa action. Therefore, our results suggest that Lpxrfa may act as a reproductive inhibitory neuropeptide in the zebrafish that interacts with Gnrh3 neurons in the brain and with gonadotropes in the pituitary, while also potentially utilizing the Kiss2/Kiss1ra pathway. © The Authors 2017. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  20. Improved actions for QCD thermodynamics on the lattice

    CERN Document Server

    Beinlich, B; Laermann, E

    1996-01-01

    Finite cut-off effects strongly influence the thermodynamics of lattice regularized QCD at high temperature in the standard Wilson formulation. We analyze the reduction of finite cut-off effects in formulations of the thermodynamics of SU(N) gauge theories with three different O(a^2) and O(a^4) improved actions. We calculate the energy density and pressure on finite lattices in leading order weak coupling perturbation theory (T\\rightarrow \\infty) and perform Monte Carlo simulations with improved SU(3) actions at non-zero g^2. Already on lattices with temporal extent N_\\tau=4 we find a strong reduction of finite cut-off effects in the high temperature limit, which persists also down to temperatures a few times the deconfinement transition temperature.

  1. Computational Model of Primary Visual Cortex Combining Visual Attention for Action Recognition.

    Directory of Open Access Journals (Sweden)

    Na Shu

    Full Text Available Humans can easily understand other people's actions through visual systems, while computers cannot. Therefore, a new bio-inspired computational model is proposed in this paper aiming for automatic action recognition. The model focuses on dynamic properties of neurons and neural networks in the primary visual cortex (V1, and simulates the procedure of information processing in V1, which consists of visual perception, visual attention and representation of human action. In our model, a family of the three-dimensional spatial-temporal correlative Gabor filters is used to model the dynamic properties of the classical receptive field of V1 simple cell tuned to different speeds and orientations in time for detection of spatiotemporal information from video sequences. Based on the inhibitory effect of stimuli outside the classical receptive field caused by lateral connections of spiking neuron networks in V1, we propose surround suppressive operator to further process spatiotemporal information. Visual attention model based on perceptual grouping is integrated into our model to filter and group different regions. Moreover, in order to represent the human action, we consider the characteristic of the neural code: mean motion map based on analysis of spike trains generated by spiking neurons. The experimental evaluation on some publicly available action datasets and comparison with the state-of-the-art approaches demonstrate the superior performance of the proposed model.

  2. Metabolic disturbance and phytochemical changes in Andrographis paniculata and possible action mode of andrographolide

    Directory of Open Access Journals (Sweden)

    Netiya Karaket

    2018-01-01

    Full Text Available Objective: To explore the effect of gibberellic acid (GA3 and its inhibitor paclobutrazol (PBZ on chemical composition and their pharmacological effects on Andrographis paniculata (Burm. f. Wall. ex Nees, and to clarify action mode of andrographolide. Methods: The chemical composition was extracted by sequential extraction with hexane, dichloromethane, ethyl acetate and methanol, respectively. Andrographolide and its derivatives were evaluated by HPLC. Moreover, the metabolic profiling was analyzed by GC-MS. Inhibitory effect of crude extracts was tested against Staphylococcus aureus using agar well diffusion method. Mode of action was tested against mutant yeast by spotting assay. Andrographolide were tested for their mode of action against eukaryotes. Results: Among different solvents, dichloromethane gave the highest yield of crude (3.58% DW, with the highest andrographolide content (8.3 mg/g DW. The effect of plant hormone (10 mg/L GA3 or PBZ on phytochemical variations and bioactivity of Andrographis paniculata was demonstrated. It was found that PBZ promoted sesquiterpene compounds about 3.5 times over than GA3 treatment. But inhibitory effect of extracts against Staphylococcus aureus was highest in GA3 treated plants; andrographolide and 14-deoxy-11,12-didehydroandrographolide contents were significantly higher than those of water or PBZ. It was found that there were 11 strains involving in ergosterol biosynthesis, V-ATPase activity and homeostasis, and superoxide detoxification process. In this regard, andrographolide might cause the damage on the lipid bilayer of yeast cell and plasma membrane by interfering ergosterol biosynthesis. Conclusions: It is found that GA3 promotes andrographolide and 14-deoxy-11,12-didehydroandrographolide content while PBZ promotes sesquiterpene content. Andrographolide might cause the damage on the lipid bilayer of yeast cell and plasma membrane by interfering ergosterol biosynthesis. It might also affect

  3. The separate roles of the reflective mind and involuntary inhibitory control in gatekeeping paranormal beliefs and the underlying intuitive confusions.

    Science.gov (United States)

    Svedholm, Annika M; Lindeman, Marjaana

    2013-08-01

    Intuitive thinking is known to predict paranormal beliefs, but the processes underlying this relationship, and the role of other thinking dispositions, have remained unclear. Study 1 showed that while an intuitive style increased and a reflective disposition counteracted paranormal beliefs, the ontological confusions suggested to underlie paranormal beliefs were predicted by individual differences in involuntary inhibitory processes. When the reasoning system was subjected to cognitive load, the ontological confusions increased, lost their relationship with paranormal beliefs, and their relationship with weaker inhibition was strongly accentuated. These findings support the argument that the confusions are mainly intuitive and that they therefore are most discernible under conditions in which inhibition is impaired, that is, when thinking is dominated by intuitive processing. Study 2 replicated the findings on intuitive and reflective thinking and paranormal beliefs. In Study 2, ontological confusions were also related to the same thinking styles as paranormal beliefs. The results support a model in which both intuitive and non-reflective thinking styles and involuntary inhibitory processes give way to embracing culturally acquired paranormal beliefs. ©2012 The British Psychological Society.

  4. Inhibitory effects of Oenothera biennis (evening primrose) seed extract on Streptococcus mutans and S. mutans-induced dental caries in rats.

    Science.gov (United States)

    Matsumoto-Nakano, M; Nagayama, K; Kitagori, H; Fujita, K; Inagaki, S; Takashima, Y; Tamesada, M; Kawabata, S; Ooshima, T

    2011-01-01

    Oenothera biennis (evening primrose) seed extract (OBSE) is known to contain polyphenols, which may possess antioxidant activities. Polyphenols extracted from several plants are reported to exhibit cariostatic activities by inhibiting mutans streptococcus growth and glucosyltransferase activities. The purpose of the present study was to examine the inhibitory effects of OBSE on the development of dental caries, both in vitro and in vivo. OBSE was investigated for its inhibitory effects on cellular aggregation, hydrophobicity, sucrose-dependent adherence and insoluble glucan synthesis. Furthermore, biofilm formation was examined in the presence of OBSE, using confocal microscopic imaging. An animal experiment was also performed to examine the in vivo effects. OBSE induced a strong aggregation of Streptococcus mutans MT8148 cells, while cell surface hydrophobicity was decreased by approximately 90% at a concentration of 0.25 mg/ml. The sucrose-dependent adherence of the MT8148 cells was also reduced by addition of OBSE, with a reduction rate of 73% seen at a concentration of 1.00 mg/ml. Additionally, confocal microscopic observations revealed the biofilm development phase to be remarkably changed in the presence of OBSE. Furthermore, insoluble glucan synthesis was significantly reduced when OBSE was present at concentrations greater than 0.03 mg/ml. In an animal experiment, the caries scores in rats given OBSE (0.05 mg/ml in drinking water) were significantly lower than those in rats given water without OBSE. Our results indicate that OBSE has inhibitory activity on dental caries. 2011 S. Karger AG, Basel.

  5. Plants from Brazilian Cerrado with potent tyrosinase inhibitory activity.

    Directory of Open Access Journals (Sweden)

    Paula Monteiro Souza

    Full Text Available The increased amount of melanin leads to skin disorders such as age spots, freckles, melasma and malignant melanoma. Tyrosinase is known to be the key enzyme in melanin production. Plants and their extracts are inexpensive and rich resources of active compounds that can be utilized to inhibit tyrosinase as well as can be used for the treatment of dermatological disorders associated with melanin hyperpigmentation. Using in vitro tyrosinase inhibitory activity assay, extracts from 13 plant species from Brazilian Cerrado were evaluated. The results showed that Pouteria torta and Eugenia dysenterica extracts presented potent in vitro tyrosinase inhibition compared to positive control kojic acid. Ethanol extract of Eugenia dysenterica leaves showed significant (p<0.05 tyrosinase inhibitory activity exhibiting the IC₅₀ value of 11.88 µg/mL, compared to kojic acid (IC₅₀ value of 13.14 µg/mL. Pouteria torta aqueous extract leaves also showed significant inhibitory activity with IC₅₀ value of 30.01 µg/mL. These results indicate that Pouteria torta and Eugenia dysenterica extracts and their isolated constituents are promising agents for skin-whitening or antimelanogenesis formulations.

  6. Selective synaptic targeting of the excitatory and inhibitory presynaptic organizers FGF22 and FGF7.

    Science.gov (United States)

    Terauchi, Akiko; Timmons, Kendall M; Kikuma, Koto; Pechmann, Yvonne; Kneussel, Matthias; Umemori, Hisashi

    2015-01-15

    Specific formation of excitatory and inhibitory synapses is crucial for proper functioning of the brain. Fibroblast growth factor 22 (FGF22) and FGF7 are postsynaptic-cell-derived presynaptic organizers necessary for excitatory and inhibitory presynaptic differentiation, respectively, in the hippocampus. For the establishment of specific synaptic networks, these FGFs must localize to appropriate synaptic locations - FGF22 to excitatory and FGF7 to inhibitory postsynaptic sites. Here, we show that distinct motor and adaptor proteins contribute to intracellular microtubule transport of FGF22 and FGF7. Excitatory synaptic targeting of FGF22 requires the motor proteins KIF3A and KIF17 and the adaptor protein SAP102 (also known as DLG3). By contrast, inhibitory synaptic targeting of FGF7 requires the motor KIF5 and the adaptor gephyrin. Time-lapse imaging shows that FGF22 moves with SAP102, whereas FGF7 moves with gephyrin. These results reveal the basis of selective targeting of the excitatory and inhibitory presynaptic organizers that supports their different synaptogenic functions. Finally, we found that knockdown of SAP102 or PSD95 (also known as DLG4), which impairs the differentiation of excitatory synapses, alters FGF7 localization, suggesting that signals from excitatory synapses might regulate inhibitory synapse formation by controlling the distribution of the inhibitory presynaptic organizer. © 2015. Published by The Company of Biologists Ltd.

  7. Macrophage migration inhibitory factor and autism spectrum disorders

    NARCIS (Netherlands)

    Grigorenko, Elena L.; Han, Summer S.; Yrigollen, Carolyn M.; Leng, Lin; Mizue, Yuka; Anderson, George M.; Mulder, Erik J.; de Bildt, Annelies; Minderaa, Ruud B.; Volkmar, Fred R.; Chang, Joseph T.; Bucala, Richard

    OBJECTIVE. Autistic spectrum disorders are childhood neurodevelopmental disorders characterized by social and communicative impairment and repetitive and stereotypical behavior. Macrophage migration inhibitory factor (MIF) is an upstream regulator of innate immunity that promotes

  8. Why (and how) should we study the interplay between emotional arousal, Theory of Mind, and inhibitory control to understand moral cognition?

    Science.gov (United States)

    Buon, Marine; Seara-Cardoso, Ana; Viding, Essi

    2016-12-01

    Findings in the field of experimental psychology and cognitive neuroscience have shed new light on our understanding of the psychological and biological bases of morality. Although a lot of attention has been devoted to understanding the processes that underlie complex moral dilemmas, attempts to represent the way in which individuals generate moral judgments when processing basic harmful actions are rare. Here, we will outline a model of morality which proposes that the evaluation of basic harmful actions relies on complex interactions between emotional arousal, Theory of Mind (ToM) capacities, and inhibitory control resources. This model makes clear predictions regarding the cognitive processes underlying the development of and ability to generate moral judgments. We draw on data from developmental and cognitive psychology, cognitive neuroscience, and psychopathology research to evaluate the model and propose several conceptual and methodological improvements that are needed to further advance our understanding of moral cognition and its development.

  9. The Inhibitory Mechanism in Learning Ambiguous Words in a Second Language.

    Science.gov (United States)

    Lu, Yao; Wu, Junjie; Dunlap, Susan; Chen, Baoguo

    2017-01-01

    Ambiguous words are hard to learn, yet little is known about what causes this difficulty. The current study aimed to investigate the relationship between the representations of new and prior meanings of ambiguous words in second language (L2) learning, and to explore the function of inhibitory control on L2 ambiguous word learning at the initial stage of learning. During a 4-day learning phase, Chinese-English bilinguals learned 30 novel English words for 30 min per day using bilingual flashcards. Half of the words to be learned were unambiguous (had one meaning) and half were ambiguous (had two semantically unrelated meanings learned in sequence). Inhibitory control was introduced as a subject variable measured by a Stroop task. The semantic representations established for the studied items were probed using a cross-language semantic relatedness judgment task, in which the learned English words served as the prime, and the targets were either semantically related or unrelated to the prime. Results showed that response latencies for the second meaning of ambiguous words were slower than for the first meaning and for unambiguous words, and that performance on only the second meaning of ambiguous words was predicted by inhibitory control ability. These results suggest that, at the initial stage of L2 ambiguous word learning, the representation of the second meaning is weak, probably interfered with by the representation of the prior learned meaning. Moreover, inhibitory control may modulate learning of the new meanings, such that individuals with better inhibitory control may more effectively suppress interference from the first meaning, and thus learn the new meaning more quickly.

  10. The Inhibitory Mechanism in Learning Ambiguous Words in a Second Language

    Directory of Open Access Journals (Sweden)

    Baoguo Chen

    2017-04-01

    Full Text Available Ambiguous words are hard to learn, yet little is known about what causes this difficulty. The current study aimed to investigate the relationship between the representations of new and prior meanings of ambiguous words in second language (L2 learning, and to explore the function of inhibitory control on L2 ambiguous word learning at the initial stage of learning. During a 4-day learning phase, Chinese–English bilinguals learned 30 novel English words for 30 min per day using bilingual flashcards. Half of the words to be learned were unambiguous (had one meaning and half were ambiguous (had two semantically unrelated meanings learned in sequence. Inhibitory control was introduced as a subject variable measured by a Stroop task. The semantic representations established for the studied items were probed using a cross-language semantic relatedness judgment task, in which the learned English words served as the prime, and the targets were either semantically related or unrelated to the prime. Results showed that response latencies for the second meaning of ambiguous words were slower than for the first meaning and for unambiguous words, and that performance on only the second meaning of ambiguous words was predicted by inhibitory control ability. These results suggest that, at the initial stage of L2 ambiguous word learning, the representation of the second meaning is weak, probably interfered with by the representation of the prior learned meaning. Moreover, inhibitory control may modulate learning of the new meanings, such that individuals with better inhibitory control may more effectively suppress interference from the first meaning, and thus learn the new meaning more quickly.

  11. Do personality traits predict individual differences in excitatory and inhibitory learning?

    Directory of Open Access Journals (Sweden)

    Zhimin eHe

    2013-05-01

    Full Text Available Conditioned inhibition (CI is demonstrated in classical conditioning when a stimulus is used to signal the omission of an otherwise expected outcome. This basic learning ability is involved in a wide range of normal behaviour - and thus its disruption could produce a correspondingly wide range of behavioural deficits. The present study employed a computer-based task to measure conditioned excitation and inhibition in the same discrimination procedure. Conditioned inhibition by summation test was clearly demonstrated. Additionally summary measures of excitatory and inhibitory learning (difference scores were calculated in order to explore how performance related to individual differences in a large sample of normal participants (n=176 following exclusion of those not meeting the basic learning criterion. The individual difference measures selected derive from two biologically-based personality theories, Gray’s reinforcement sensitivity theory (1982 and Eysenck’s psychoticism, extraversion and neuroticism theory (1991. Following the behavioural tasks, participants completed the behavioural inhibition system/behavioural activation system scales (BIS/BAS and the Eysenck personality questionnaire revised short scale (EPQ-RS. Analyses of the relationship between scores on each of the scales and summary measures of excitatory and inhibitory learning suggested that those with higher BAS (specifically the drive sub-scale and higher EPQ-RS neuroticism showed reduced levels of excitatory conditioning. Inhibitory conditioning was similarly attenuated in those with higher EPQ-RS neuroticism, as well as in those with higher BIS scores. Thus the findings are consistent with higher levels of neuroticism being accompanied by generally impaired associative learning, both inhibitory and excitatory. There was also evidence for some dissociation in the effects of behavioural activation and behavioural inhibition on excitatory and inhibitory learning respectively.

  12. Experience of action depends on intention, not body movement

    DEFF Research Database (Denmark)

    Jensen, Mads; Vagnoni, Eleonora; Overgaard, Morten

    2014-01-01

    in memory. We found that recall of a voluntary action was unaffected by an incongruent involuntary movement. In contrast, recall of an involuntary movement was strongly influenced by an incongruent voluntary action. Our results demonstrate an “intentional capture” of body movement by voluntary actions......, in support of intentional theories of agency, but contrary to reconstructive theories. When asked to recall both actions and movements, people's responses are shaped by memory of what they intended to do, rather than by how their body moved....... effects that they produce. Intentions would then be mere confabulations, and not bona fide experiences. Previous work on voluntary action has focused on immediate experiences of authorship, and few studies have considered memory for voluntary actions. We devised an experiment in which both voluntary...

  13. Single-molecule analysis of inhibitory pausing states of V1-ATPase.

    Science.gov (United States)

    Uner, Naciye Esma; Nishikawa, Yoshihiro; Okuno, Daichi; Nakano, Masahiro; Yokoyama, Ken; Noji, Hiroyuki

    2012-08-17

    V(1)-ATPase, the hydrophilic V-ATPase domain, is a rotary motor fueled by ATP hydrolysis. Here, we found that Thermus thermophilus V(1)-ATPase shows two types of inhibitory pauses interrupting continuous rotation: a short pause (SP, 4.2 s) that occurred frequently during rotation, and a long inhibitory pause (LP, >30 min) that terminated all active rotations. Both pauses occurred at the same angle for ATP binding and hydrolysis. Kinetic analysis revealed that the time constants of inactivation into and activation from the SP were too short to represent biochemically predicted ADP inhibition, suggesting that SP is a newly identified inhibitory state of V(1)-ATPase. The time constant of inactivation into LP was 17 min, consistent with one of the two time constants governing the inactivation process observed in bulk ATPase assay. When forcibly rotated in the forward direction, V(1) in LP resumed active rotation. Solution ADP suppressed the probability of mechanical activation, suggesting that mechanical rotation enhanced inhibitory ADP release. These features were highly consistent with mechanical activation of ADP-inhibited F(1), suggesting that LP represents the ADP-inhibited state of V(1)-ATPase. Mechanical activation largely depended on the direction and angular displacement of forced rotation, implying that V(1)-ATPase rotation modulates the off rate of ADP.

  14. Inhibitory mechanism of chroman compound on LPS-induced nitric oxide production and nuclear factor-κB activation

    International Nuclear Information System (INIS)

    Kim, Byung Hak; Reddy, Alavala Matta; Lee, Kum-Ho; Chung, Eun Yong; Cho, Sung Min; Lee, Heesoon; Min, Kyung Rak; Kim, Youngsoo

    2004-01-01

    6-Hydroxy-7-methoxychroman-2-carboxylic acid phenylamide (KL-1156) is a novel chemically synthetic compound. In the present study, the chroman KL-1156 compound was found to inhibit lipopolysaccharide (LPS)-induced nitric oxide production in macrophages RAW 264.7. KL-1156 compound attenuated LPS-induced synthesis of both mRNA and protein of inducible nitric oxide synthase (iNOS), in parallel, and inhibited LPS-induced iNOS promoter activity, indicating that the chroman compound down-regulated iNOS expression at transcription level. As a mechanism of the anti-inflammatory action shown by KL-1156 compound, suppression of nuclear factor (NF)-κB has been documented. KL-1156 compound exhibited a dose-dependent inhibitory effect on LPS-induced NF-κB transcriptional activity in macrophages RAW 264.7. Furthermore, the compound inhibited LPS-induced nuclear translocation of NF-κB p65 and DNA binding activity of NF-κB complex, in parallel, but did not affect IκBα degradation. Taken together, this study demonstrated that chroman KL-1156 compound interfered with nuclear translocation step of NF-κB p65, which was attributable to its anti-inflammatory action

  15. Towards a strong virtue ethics for nursing practice.

    Science.gov (United States)

    Armstrong, Alan E

    2006-07-01

    Illness creates a range of negative emotions in patients including anxiety, fear, powerlessness, and vulnerability. There is much debate on the 'therapeutic' or 'helping' nurse-patient relationship. However, despite the current agenda regarding patient-centred care, the literature concerning the development of good interpersonal responses and the view that a satisfactory nursing ethics should focus on persons and character traits rather than actions, nursing ethics is dominated by the traditional obligation, act-centred theories such as consequentialism and deontology. I critically examine these theories and the role of duty-based notions in both general ethics and nursing practice. Because of well-established flaws, I conclude that obligation-based moral theories are incomplete and inadequate for nursing practice. I examine the work of Hursthouse on virtue ethics' action guidance and the v-rules. I argue that the moral virtues and a strong (action-guiding) version of virtue ethics provide a plausible and viable alternative for nursing practice. I develop an account of a virtue-based helping relationship and a virtue-based approach to nursing. The latter is characterized by three features: (1) exercising the moral virtues such as compassion; (2) using judgement; and (3) using moral wisdom, understood to include at least moral perception, moral sensitivity, and moral imagination. Merits and problems of the virtue-based approach are examined. I relate the work of MacIntyre to nursing and I conceive nursing as a practice: nurses who exercise the virtues and seek the internal goods help to sustain the practice of nursing and thus prevent the marginalization of the virtues. The strong practice-based version of virtue ethics proposed is context-dependent, particularist, and relational. Several areas for future philosophical inquiry and empirical nursing research are suggested to develop this account yet further.

  16. Action plan against declining vineyards: An innovative approach

    Directory of Open Access Journals (Sweden)

    Riou Christophe

    2016-01-01

    Full Text Available Declining vineyards are assessed by a multi-year decrease in vine productivity and/or its sudden premature or gradual death, based on multiple factors. Since 2015, the French wine sector has been working on an original study to identify new research avenues while launching an innovative action plan to combat vineyard decline. First, a statistical analysis enabled to estimate research efforts in the different countries. 70 factors susceptible to contribute to vineyard decline were then identified by analyzing more than 500 publications. These factors are biological, physical or linked to growing practices. While the role of pathogens is fairly well-known, the impact of the land plot or the soil on decline is less understood. Secondly, a prospective methodology was used to better identify viticulture system factors and levers affecting vines. It was thus demonstrated that yield and longevity are strongly linked to agronomy, economic variables and plant matter, plant physiology, disease, etc... These are the key issues and leverage actions to combat more strongly vineyard decline. The matrix analysis was then complemented by interviews and statistical data to imagine leverage actions. The strategic action plan is focused on four objectives: promoting training of good practices, improving plant production organization, developing vineyard observation networks, implementing an innovative research plan.

  17. Inhibitory effect of bofutsushosan (fang feng tong sheng san) on glucose transporter 5 function in vitro.

    Science.gov (United States)

    Gao, Shengli; Satsu, Hideo; Makino, Toshiaki

    2018-03-01

    Bofutsushosan (BTS; fang feng tong sheng san in Chinese) is a formula in traditional Japanese Kampo medicine and Chinese medicine comprising eighteen crude drugs, and is used to treat obesity and metabolic syndrome. Fructose is contained in refreshing beverages as high-fructose corn syrup, and is associated with obesity. Fructose is absorbed via glucose transporter 5 (GLUT5) in the intestine. Therefore, the inhibition of GLUT5 is considered to be a target of obesity drugs. We evaluated the inhibitory effects of BTS extract and its constituents on fructose uptake using Chinese hamster ovary K1 cells, i.e., cells stably expressing GLUT5. Boiled water extract of BTS significantly suppressed GLUT5 function in a concentration-dependent manner without cytotoxicities. Among 18 components of BTS, the boiled water extracts of the rhizome of Zingiber officinale, the root and rhizome of Saposhnikovia divaricata, and the root of Platycodon grandiflorum exhibited significant inhibitory effects on fructose uptake with IC 50 values of 314, 119 and 475 µg/ml, respectively. Among the constituents of the rhizome of Z. officinale extract, 6-gingerol significantly inhibited GLUT5 with an IC 50 value of 39 µM, while 6-shogaol exhibited a significant but weak inhibition on GLUT5 at 100 µM. One of the mechanisms of action of BTS may be the inhibition of fructose absorption in the intestine, and one of the active components of BTS is the rhizome of Z. officinale and 6-gingerol.

  18. Action of bicyclic isoxazole GABA analogues on GABA transporters and its relation to anticonvulsant activity

    DEFF Research Database (Denmark)

    Bolvig, T; Larsson, O M; Pickering, D S

    1999-01-01

    The inhibitory action of bicyclic isoxazole gamma-aminobutyric acid (GABA) analogues and their 4,4-diphenyl-3-butenyl (DPB) substituted derivatives has been investigated in cortical neurones and astrocytes as well as in human embryonic kidney (HEK 293) cells transiently expressing either mouse GA...... anticonvulsant activity, lack of proconvulsant activity and the ability of THPO to increase extracellular GABA concentration, indicate that these bicyclic isoxazole GABA analogues and their DPB derivatives may be useful lead structures in future search for new antiepileptic drugs....

  19. Perception-Action in children with ASD

    Directory of Open Access Journals (Sweden)

    Claes eVon Hofsten

    2012-12-01

    Full Text Available How do disturbances to perception and action relate to the deficiencies expressed by children with autism? The ability to predict what is going to happen next is crucial for the construction of all actions and children develop these predictive abilities early in development. Children with autism, however, are deficient in the ability to foresee future events and to plan movements and movement sequences. They are also deficient in the understanding of other people’s actions. This includes communicative actions as they are ultimately based on movements. Today there are two promising neurobiological interpretation of ASD. First, there is strong evidence that the Mirror Neuron System (MNS is impaired. As stated by this hypothesis, action production and action understanding are intimately related. Both these functions rely on predictive models of the sensory consequences of actions and depend on connectivity between the parietal and pre-motor areas. Secondly, action prediction is accomplished through a system that includes a loop from the posterior parietal cortex through the cerebellum and back to the premotor and motor areas of the brain. Impairment of this loop is probably also part of the explanation of the prediction problems in children with ASD. Both the cortico-cerebellar loop and the MNS rely on distant neural connections. There are multiple evidence that such connections are weak in children with autism.

  20. Novel nootropic dipeptide Noopept increases inhibitory synaptic transmission in CA1 pyramidal cells.

    Science.gov (United States)

    Kondratenko, Rodion V; Derevyagin, Vladimir I; Skrebitsky, Vladimir G

    2010-05-31

    Effects of newly synthesized nootropic and anxiolytic dipeptide Noopept on inhibitory synaptic transmission in hippocampal CA1 pyramidal cells were investigated using patch-clamp technique in whole-cell configuration. Bath application of Noopept (1 microM) significantly increased the frequency of spike-dependant spontaneous IPSCs whereas spike-independent mIPSCs remained unchanged. It was suggested that Noopept mediates its effect due to the activation of inhibitory interneurons terminating on CA1 pyramidal cells. Results of current clamp recording of inhibitory interneurons residing in stratum radiatum confirmed this suggestion. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

  1. Inhibitory action of some essential oils and phytochemicals on the growth of various moulds isolated from foods

    Directory of Open Access Journals (Sweden)

    Evandro Leite de Souza

    2005-03-01

    Full Text Available The aim of this study was to determine the sensitivity profile of mould strains isolated from foods to some essential oils and phytochemicals. The assayed mould strains were: Fusarium spp., Rhizopus spp., Aspergillus flavus, A. niger and Penicillium spp. According to results, Lippia alba N.E. Brown, Peumus boldus Molina, Lippia microphylla Phil., Citrus limon Risso and Cymbopogon citratus Stapf. essential oil and the phytochemicals citral, eugenol and mircene showed prominent antimould activity. Among the products that evidenced antimould activity, citral and eugenol showed the lowest minimum inhibitory concentrations, which was 1% and 4%, respectively, for the most of the tested mould strains.O objetivo deste estudo foi determinar o perfil de sensibilidade de cepas de fungos filamentosos isolados de alimento a alguns óleos essenciais e fitoconstituintes. As cepas fúngicas utilizadas nos ensaios antimicrobianos foram: Fusarium spp., Rhizopus spp., Aspergillus flavus, A. niger e Penicillium spp. De acordo com os resultados obtidos, os óleos essenciais de L. Alba N.R. Brown, P. boldus Molina, L. microphylla Phill, C. limon Risso e C. citratus Stapf. e os fitoconstituintes citral, eugenol e mirceno mostraram destacada atividade antifúngica. Dentre os produtos que apresentaram atividade antifúngica, o citral e eugenol mostraram as menores CIM's, as quais foram 1% e 4%, respectivamente, para a maioria das cepas fúngicas testadas.

  2. Correlation between enzymes inhibitory effects and antioxidant ...

    African Journals Online (AJOL)

    ... and phytochemical content of fractions was investigated. The n-butanol fraction showed significant α-glucosidase and α-amylase inhibitory effects (IC50 values 15.1 and 39.42 μg/ml, respectively) along with the remarkable antioxidant activity when compared to the other fractions. High performance liquid chromatography ...

  3. PPARγ partial agonist GQ-16 strongly represses a subset of genes in 3T3-L1 adipocytes

    Energy Technology Data Exchange (ETDEWEB)

    Milton, Flora Aparecida [Faculdade de Ciências da Saúde, Laboratório de Farmacologia Molecular, Universidade de Brasília (Brazil); Genomic Medicine, Houston Methodist Research Institute, Houston, TX (United States); Cvoro, Aleksandra [Genomic Medicine, Houston Methodist Research Institute, Houston, TX (United States); Amato, Angelica A. [Faculdade de Ciências da Saúde, Laboratório de Farmacologia Molecular, Universidade de Brasília (Brazil); Sieglaff, Douglas H.; Filgueira, Carly S.; Arumanayagam, Anithachristy Sigamani [Genomic Medicine, Houston Methodist Research Institute, Houston, TX (United States); Caro Alves de Lima, Maria do; Rocha Pitta, Ivan [Laboratório de Planejamento e Síntese de Fármacos – LPSF, Universidade Federal de Pernambuco (Brazil); Assis Rocha Neves, Francisco de [Faculdade de Ciências da Saúde, Laboratório de Farmacologia Molecular, Universidade de Brasília (Brazil); Webb, Paul, E-mail: pwebb@HoustonMethodist.org [Genomic Medicine, Houston Methodist Research Institute, Houston, TX (United States)

    2015-08-28

    Thiazolidinediones (TZDs) are peroxisome proliferator-activated receptor gamma (PPARγ) agonists that improve insulin resistance but trigger side effects such as weight gain, edema, congestive heart failure and bone loss. GQ-16 is a PPARγ partial agonist that improves glucose tolerance and insulin sensitivity in mouse models of obesity and diabetes without inducing weight gain or edema. It is not clear whether GQ-16 acts as a partial agonist at all PPARγ target genes, or whether it displays gene-selective actions. To determine how GQ-16 influences PPARγ activity on a gene by gene basis, we compared effects of rosiglitazone (Rosi) and GQ-16 in mature 3T3-L1 adipocytes using microarray and qRT-PCR. Rosi changed expression of 1156 genes in 3T3-L1, but GQ-16 only changed 89 genes. GQ-16 generally showed weak effects upon Rosi induced genes, consistent with partial agonist actions, but a subset of modestly Rosi induced and strongly repressed genes displayed disproportionately strong GQ-16 responses. PPARγ partial agonists MLR24 and SR1664 also exhibit disproportionately strong effects on transcriptional repression. We conclude that GQ-16 displays a continuum of weak partial agonist effects but efficiently represses some negatively regulated PPARγ responsive genes. Strong repressive effects could contribute to physiologic actions of GQ-16. - Highlights: • GQ-16 is an insulin sensitizing PPARγ ligand with reduced harmful side effects. • GQ-16 displays a continuum of weak partial agonist activities at PPARγ-induced genes. • GQ-16 exerts strong repressive effects at a subset of genes. • These inhibitor actions should be evaluated in models of adipose tissue inflammation.

  4. PPARγ partial agonist GQ-16 strongly represses a subset of genes in 3T3-L1 adipocytes

    International Nuclear Information System (INIS)

    Milton, Flora Aparecida; Cvoro, Aleksandra; Amato, Angelica A.; Sieglaff, Douglas H.; Filgueira, Carly S.; Arumanayagam, Anithachristy Sigamani; Caro Alves de Lima, Maria do; Rocha Pitta, Ivan; Assis Rocha Neves, Francisco de; Webb, Paul

    2015-01-01

    Thiazolidinediones (TZDs) are peroxisome proliferator-activated receptor gamma (PPARγ) agonists that improve insulin resistance but trigger side effects such as weight gain, edema, congestive heart failure and bone loss. GQ-16 is a PPARγ partial agonist that improves glucose tolerance and insulin sensitivity in mouse models of obesity and diabetes without inducing weight gain or edema. It is not clear whether GQ-16 acts as a partial agonist at all PPARγ target genes, or whether it displays gene-selective actions. To determine how GQ-16 influences PPARγ activity on a gene by gene basis, we compared effects of rosiglitazone (Rosi) and GQ-16 in mature 3T3-L1 adipocytes using microarray and qRT-PCR. Rosi changed expression of 1156 genes in 3T3-L1, but GQ-16 only changed 89 genes. GQ-16 generally showed weak effects upon Rosi induced genes, consistent with partial agonist actions, but a subset of modestly Rosi induced and strongly repressed genes displayed disproportionately strong GQ-16 responses. PPARγ partial agonists MLR24 and SR1664 also exhibit disproportionately strong effects on transcriptional repression. We conclude that GQ-16 displays a continuum of weak partial agonist effects but efficiently represses some negatively regulated PPARγ responsive genes. Strong repressive effects could contribute to physiologic actions of GQ-16. - Highlights: • GQ-16 is an insulin sensitizing PPARγ ligand with reduced harmful side effects. • GQ-16 displays a continuum of weak partial agonist activities at PPARγ-induced genes. • GQ-16 exerts strong repressive effects at a subset of genes. • These inhibitor actions should be evaluated in models of adipose tissue inflammation

  5. Fruit Wines Inhibitory Activity Against α-Glucosidase.

    Science.gov (United States)

    Cakar, Uros; Grozdanic, Nada; Petrovic, Aleksandar; Pejin, Boris; Nastasijevic, Branislav; Markovic, Bojan; Dordevic, Brizita

    2017-01-01

    Fruit wines are well known for their profound health-promoting properties including both enzyme activations and inhibitions. They may act preventive in regard to diabetes melitus and other chronic diseases. Potential α-glucosidase inhibitory activity of fruit wines made from blueberry, black chokeberry, blackberry, raspberry and sour cherry was the subject of this study. In order to increase the alcohol content due to enriched extraction of total phenolics, sugar was added in the fruit pomace of the half of the examined fruit wine samples. Compared with acarbose used as a positive control (IC50 = 73.78 µg/mL), all fruit wine samples exhibited higher α-glucosidase inhibitory activity. Indeed, blueberry wine samples stood out, both prepared with IC50 = 24.14 µg/mL, lyophilised extract yield 3.23% and without IC50 = 46.39 µg/mL, lyophilised extract yield 2.89% and with addition of sugar before fermentation. Chlorogenic acid predominantly contributed to α-glucosidase inhibitory activity of the blueberry, black chokeberry and sour cherry wine samples. However, ellagic acid, a potent α-glucosidase inhibitor possessing a planar structure, only slightly affected the activity of the blueberry wine samples, due to the lower concentration. In addition to this, molecular docking study of chlorogenic acid pointed out the importance of binding energy (-8.5 kcal/mol) for the inhibition of the enzyme. In summary, fruit wines made from blueberry should be primarily taken into consideration as a medicinal food targeting diabetes mellitus type 2 in the early stage, if additional studies would confirm their therapeutic potential for the control of postprandial hyperglycemia. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  6. Can Working Memory and Inhibitory Control Predict Second Language Learning in the Classroom?

    Directory of Open Access Journals (Sweden)

    Jared A. Linck

    2015-10-01

    Full Text Available The role of executive functioning in second language (L2 aptitude remains unclear. Whereas some studies report a relationship between working memory (WM and L2 learning, others have argued against this association. Similarly, being bilingual appears to benefit inhibitory control, and individual differences in inhibitory control are related to online L2 processing. The current longitudinal study examines whether these two components of executive functioning predict learning gains in an L2 classroom context using a pretest/posttest design. We assessed 25 university students in language courses, who completed measures of WM and inhibitory control. They also completed a proficiency measure at the beginning and end of a semester and reported their grade point average (GPA. WM was positively related to L2 proficiency and learning, but inhibitory control was not. These results support the notion that WM is an important component of L2 aptitude, particularly for predicting the early stages of L2 classroom learning.

  7. Multiple modes of action potential initiation and propagation in mitral cell primary dendrite

    DEFF Research Database (Denmark)

    Chen, Wei R; Shen, Gongyu Y; Shepherd, Gordon M

    2002-01-01

    recordings with computational modeling to analyze action-potential initiation and propagation in the primary dendrite. In response to depolarizing current injection or distal olfactory nerve input, fast Na(+) action potentials were recorded along the entire length of the primary dendritic trunk. With weak......-to-moderate olfactory nerve input, an action potential was initiated near the soma and then back-propagated into the primary dendrite. As olfactory nerve input increased, the initiation site suddenly shifted to the distal primary dendrite. Multi-compartmental modeling indicated that this abrupt shift of the spike......-initiation site reflected an independent thresholding mechanism in the distal dendrite. When strong olfactory nerve excitation was paired with strong inhibition to the mitral cell basal secondary dendrites, a small fast prepotential was recorded at the soma, which indicated that an action potential was initiated...

  8. Inhibitory Effects of Flavonoids from Spatholobus suberectus on Sortase A and Sortase A-Mediated Aggregation of Streptococcus mutans.

    Science.gov (United States)

    Park, Wanki; Ahn, Chan-Hong; Cho, Hyunjoo; Kim, Chang-Kwon; Shin, Jongheon; Oh, Ki-Bong

    2017-08-28

    Seven flavonoids were isolated from Spatholobus suberectus via repetitive column chromatography and high-performance liquid chromatography. The chemical structures of these compounds were identified by spectroscopic analysis and comparison with values reported in the literature. Among the flavonoids tested, 7-hydroxy-6-methoxyflavanone ( 1 ) and formononetin ( 4 ) exhibited strong inhibitory activity against Streptococcus mutans SrtA, with IC 50 values of 46.1 and 41.8 µM, respectively, but did not affect cell viability. The onset and magnitude of inhibition of saliva-induced aggregation in S. mutans treated with compounds 1 and 4 were comparable to the behavior of a srtA -deletion mutant without treatment.

  9. Gauge-invariant master field in U(∞) LGT: A pathway from the strong to weak coupling phases

    International Nuclear Information System (INIS)

    Kazakov, V.A.; Migdal, A.A.

    1987-01-01

    We propose and test a new computational method for SU(∞) lattice gauge and spin theories. It is based on calculation of the effective action depending only on N (rather than N 2 ) gauge invariant degrees of freedom, by means of some modification of the strong coupling expansion. We show using the example of a one-plaquette model that the stationary point equation for this action describes the weak coupling phase as well as the strong coupling phase. It is argued that such an equation predicts a phase transition for D-dimensional gauge theory, in accordance with Monte Carlo data. (orig.)

  10. Inhibitory Control Mediates the Association between Perceived Stress and Secure Relationship Quality

    OpenAIRE

    Toria Herd; Mengjiao Li; Dominique Maciejewski; Jacob Lee; Kirby Deater-Deckard; Brooks King-Casas; Jungmeen Kim-Spoon

    2018-01-01

    Past research has demonstrated negative associations between exposure to stressors and quality of interpersonal relationships among children and adolescents. Nevertheless, underlying mechanisms of this association remain unclear. Chronic stress has been shown to disrupt prefrontal functioning in the brain, including inhibitory control abilities, and evidence is accumulating that inhibitory control may play an important role in secure interpersonal relationship quality, including peer problems...

  11. Inhibitory and Working Memory Demands of the Day-Night Task in Children

    Science.gov (United States)

    Simpson, Andrew; Riggs, Kevin J.

    2005-01-01

    Gerstadt, Hong, and Diamond (1994) investigated the development of inhibitory control in children aged 3 1/2 - 7 years using the day-night task. In two studies we build on Gerstadt et al.'s findings with a measure of inhibitory control that can be used throughout childhood. In Study 1 (twenty-four 3 1/2-year-olds and sixteen 5-year-olds) we…

  12. Action-angle variable for the Gel'fand-Dikii flows

    International Nuclear Information System (INIS)

    Beals, R.; Sattinger, D.H.

    1992-01-01

    Using the scattering transform for nth order linear scalar operators, the Poisson bracket found by Gel'fans and Dikii, which generalizes the Gardner Poisson bracket for the KdV hierarchy, is computed on the scattering side. Action-angle variables are then constructed. Using this, complete integrability is demonstrated in the strong sense. Real action-angle variables are constructed in the self-adjoint case. (orig.)

  13. Disciplinary action by medical boards and prior behavior in medical school.

    Science.gov (United States)

    Papadakis, Maxine A; Teherani, Arianne; Banach, Mary A; Knettler, Timothy R; Rattner, Susan L; Stern, David T; Veloski, J Jon; Hodgson, Carol S

    2005-12-22

    Evidence supporting professionalism as a critical measure of competence in medical education is limited. In this case-control study, we investigated the association of disciplinary action against practicing physicians with prior unprofessional behavior in medical school. We also examined the specific types of behavior that are most predictive of disciplinary action against practicing physicians with unprofessional behavior in medical school. The study included 235 graduates of three medical schools who were disciplined by one of 40 state medical boards between 1990 and 2003 (case physicians). The 469 control physicians were matched with the case physicians according to medical school and graduation year. Predictor variables from medical school included the presence or absence of narratives describing unprofessional behavior, grades, standardized-test scores, and demographic characteristics. Narratives were assigned an overall rating for unprofessional behavior. Those that met the threshold for unprofessional behavior were further classified among eight types of behavior and assigned a severity rating (moderate to severe). Disciplinary action by a medical board was strongly associated with prior unprofessional behavior in medical school (odds ratio, 3.0; 95 percent confidence interval, 1.9 to 4.8), for a population attributable risk of disciplinary action of 26 percent. The types of unprofessional behavior most strongly linked with disciplinary action were severe irresponsibility (odds ratio, 8.5; 95 percent confidence interval, 1.8 to 40.1) and severely diminished capacity for self-improvement (odds ratio, 3.1; 95 percent confidence interval, 1.2 to 8.2). Disciplinary action by a medical board was also associated with low scores on the Medical College Admission Test and poor grades in the first two years of medical school (1 percent and 7 percent population attributable risk, respectively), but the association with these variables was less strong than that with

  14. Npas4 regulates excitatory-inhibitory balance within neural circuits through cell-type-specific gene programs.

    Science.gov (United States)

    Spiegel, Ivo; Mardinly, Alan R; Gabel, Harrison W; Bazinet, Jeremy E; Couch, Cameron H; Tzeng, Christopher P; Harmin, David A; Greenberg, Michael E

    2014-05-22

    The nervous system adapts to experience by inducing a transcriptional program that controls important aspects of synaptic plasticity. Although the molecular mechanisms of experience-dependent plasticity are well characterized in excitatory neurons, the mechanisms that regulate this process in inhibitory neurons are only poorly understood. Here, we describe a transcriptional program that is induced by neuronal activity in inhibitory neurons. We find that, while neuronal activity induces expression of early-response transcription factors such as Npas4 in both excitatory and inhibitory neurons, Npas4 activates distinct programs of late-response genes in inhibitory and excitatory neurons. These late-response genes differentially regulate synaptic input to these two types of neurons, promoting inhibition onto excitatory neurons while inducing excitation onto inhibitory neurons. These findings suggest that the functional outcomes of activity-induced transcriptional responses are adapted in a cell-type-specific manner to achieve a circuit-wide homeostatic response. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Phenotypic characterisation and assessment of the inhibitory ...

    African Journals Online (AJOL)

    Fred

    inhibitory potential of Lactobacillus isolates from different sources. Oyetayo, V.O.. Department of ... Six strains of Lactobacillus spp. were isolated from fermenting corn slurry, fresh cow milk, and the faeces of pig, albino rat, and human ... the growth of some pathogens by Lactobacillus reuteri BSA 13, obtained from pig faeces.

  16. Inhibitory Effects of 5,6,7-Trihydroxyflavones on Tyrosinase

    Directory of Open Access Journals (Sweden)

    Jun Kawabata

    2007-01-01

    Full Text Available Baicalein (1, 6-hydroxyapigenin (6, 6-hydroxygalangin (13 and 6-hydroxy-kaempferol (14, which are naturally occurring flavonoids from a set of 14 hydroxy-flavones tested, exhibited high inhibitory effects on tyrosinase with respect to L-DOPA,while each of the 5,6,7-trihydroxyflavones 1, 6, 13 or 14 acted as a cofactor tomonophenolase. Moreover, 6-hydroxykaempferol (14 showed the highest activity andwas a competitive inhibitor of tyrosinase compared to L-DOPA. 5,6,7-Trihydroxyflavones 1, 6, 13 or 14 showed also high antioxidant activities. Hence, weconclude that the 5,6,7-trihydroxy-flavones are useful as good depigmentation agentswith inhibitory effects in addition to their antioxidant properties.

  17. From action planning and plan enactment to fruit consumption: moderated mediation effects.

    Science.gov (United States)

    Kasten, Stefanie; van Osch, Liesbeth; Eggers, Sander Matthijs; de Vries, Hein

    2017-10-23

    Sufficient fruit consumption is beneficial for a healthy live. While many Dutch adults intent to eat the recommended amount of fruit, only 5-10% of the population actually adheres to the recommendation. One mechanism that can help to narrow this gap between intention and actual fruit consumption is action planning. However, action planning is only assumed to be effective if plans are enacted. This study assessed which action plans are made and enacted, and further aimed to investigate two main hypotheses: 1. the effect of action planning (at T1) on fruit consumption (at T2) is mediated by plan enactment (at T3); 2. positive intentions (2a), high self-efficacy (2b) and a strong habit to eat fruit (2c) enhance the mediation of plan enactment, whereas a strong habit to eat snacks (2d) hinders the mediation of plan enactment. This study was a self-reported longitudinal online survey study. A total of 428 participants filled in a survey, measuring demographic factors (e.g. gender, age, education level), several socio-cognitive constructs (i.e. attitudes, self-efficacy, habit, action planning, plan enactment), and fruit consumption, at three points in time (baseline, after 1 month, and after 3 months). Mediation and moderated mediation analyses were used to investigate the planning-plan enactment- fruit consumption relationship. Up to 70% of the participants reported to have enacted their T1 action plans at T2. Action planning on fruit consumption was fully mediated by plan enactment (Hypothesis 1). All four proposed moderators (i.e. intention, self-efficacy, habit to consume fruit, and habit to consume snacks) significantly influenced the mediation (Hypotheses 2a-2d). Mediation of plan enactment was only present with high levels of intention, high levels of self-efficacy, strong habits to eat fruit, and weak habits to eat snacks. The study suggests the importance of plan enactment for fruit consumption. Furthermore, it emphasizes the necessity of facilitating factors

  18. Inhibitory activity of an extract from a marine bacterium Halomonas sp. HSB07 against the red-tide microalga Gymnodinium sp. (Pyrrophyta)

    Science.gov (United States)

    Liu, Juan; Li, Fuchao; Liu, Ling; Jiang, Peng; Liu, Zhaopu

    2013-11-01

    In recent years, red tides occurred frequently in coastal areas worldwide. Various methods based on the use of clay, copper sulfate, and bacteria have been successful in controlling red tides to some extent. As a new defensive agent, marine microorganisms are important sources of compounds with potent inhibitory bioactivities against red-tide microalgae, such as Gymnodinium sp. (Pyrrophyta). In this study, we isolated a marine bacterium, HSB07, from seawater collected from Hongsha Bay, Sanya, South China Sea. Based on its 16S rRNA gene sequence and biochemical characteristics, the isolated strain HSB07 was identified as a member of the genus Halomonas. A crude ethyl acetate extract of strain HSB07 showed moderate inhibition activity against Gymnodinium sp. in a bioactive prescreening experiment. The extract was further separated into fractions A, B, and C by silica gel column chromatography. Fractions B and C showed strong inhibition activities against Gymnodinium. This is the first report of inhibitory activity of secondary metabolites of a Halomonas bacterium against a red-tide-causing microalga.

  19. Cholecystokinin receptor-1 mediates the inhibitory effects of exogenous cholecystokinin octapeptide on cellular morphine dependence

    Directory of Open Access Journals (Sweden)

    Wen Di

    2012-06-01

    Full Text Available Abstract Background Cholecystokinin octapeptide (CCK-8, the most potent endogenous anti-opioid peptide, has been shown to regulate the processes of morphine dependence. In our previous study, we found that exogenous CCK-8 attenuated naloxone induced withdrawal symptoms. To investigate the precise effect of exogenous CCK-8 and the role of cholecystokinin (CCK 1 and/or 2 receptors in morphine dependence, a SH-SY5Y cell model was employed, in which the μ-opioid receptor, CCK1/2 receptors, and endogenous CCK are co-expressed. Results Forty-eight hours after treating SH-SY5Y cells with morphine (10 μM, naloxone (10 μM induced a cAMP overshoot, indicating that cellular morphine dependence had been induced. The CCK receptor and endogenous CCK were up-regulated after chronic morphine exposure. The CCK2 receptor antagonist (LY-288,513 at 1–10 μM inhibited the naloxone-precipitated cAMP overshoot, but the CCK1 receptor antagonist (L-364,718 did not. Interestingly, CCK-8 (0.1-1 μM, a strong CCK receptor agonist, dose-dependently inhibited the naloxone-precipitated cAMP overshoot in SH-SY5Y cells when co-pretreated with morphine. The L-364,718 significantly blocked the inhibitory effect of exogenous CCK-8 on the cAMP overshoot at 1–10 μM, while the LY-288,513 did not. Therefore, the CCK2 receptor appears to be necessary for low concentrations of endogenous CCK to potentiate morphine dependence in SH-SY5Y cells. An additional inhibitory effect of CCK-8 at higher concentrations appears to involve the CCK1 receptor. Conclusions This study reveals the difference between exogenous CCK-8 and endogenous CCK effects on the development of morphine dependence, and provides the first evidence for the participation of the CCK1 receptor in the inhibitory effects of exogenous CCK-8 on morphine dependence.

  20. Self-esteem in action

    DEFF Research Database (Denmark)

    Strandell, Jacob

    2017-01-01

    Self-esteem research has been in “crisis” during the last decade, due to the lack of strong, consistent correlations between self-esteem and behavioral outcomes. Some researchers have interpreted this as indicating that self-esteem is inconsequential in many important areas of life. However, the ......-construction, and thus performative. Future self-esteem research and theory should therefore focus on how people seek to enact, maintain, or defend a desired identity through performative actions....

  1. Chronic caffeine prevents changes in inhibitory avoidance memory and hippocampal BDNF immunocontent in middle-aged rats.

    Science.gov (United States)

    Sallaberry, Cássia; Nunes, Fernanda; Costa, Marcelo S; Fioreze, Gabriela T; Ardais, Ana Paula; Botton, Paulo Henrique S; Klaudat, Bruno; Forte, Thomás; Souza, Diogo O; Elisabetsky, Elaine; Porciúncula, Lisiane O

    2013-01-01

    Beneficial effects of caffeine on memory processes have been observed in animal models relevant to neurodegenerative diseases and aging, although the underlying mechanisms remain unknown. Because brain-derived neurotrophic factor (BDNF) is associated with memory formation and BDNF's actions are modulated by adenosine receptors, the molecular targets for the psychostimulant actions of caffeine, we here compare the effects of chronic caffeine (1 mg/mL drinking solution for 30 days) on short- and long term memory and on levels of hippocampal proBDNF, mature BDNF, TrkB and CREB in young (3 month old) and middle-aged (12 month old) rats. Caffeine treatment substantially reduced i) age-related impairments in the two types of memory in an inhibitory avoidance paradigm, and ii) parallel increases in hippocampal BDNF levels. In addition, chronic caffeine increased proBDNF and CREB concentrations, and decreased TrkB levels, in hippocampus regardless of age. These data provide new evidence in favor of the hypothesis that modifications in BDNF and related proteins in the hippocampus contribute to the pro-cognitive effects of caffeine on age-associated losses in memory encoding. This article is part of a Special Issue entitled 'Cognitive Enhancers'. Copyright © 2012 Elsevier Ltd. All rights reserved.

  2. Effective interactions in strongly-coupled quantum systems

    International Nuclear Information System (INIS)

    Chen, J.M.C.

    1986-01-01

    In this thesis, they study the role of effective interactions in strongly-coupled Fermi systems where the short-range correlations introduce difficulties requiring special treatment. The correlated basis function method provides the means to incorporate the short-range correlations and generate the matrix elements of the Hamiltonian and identity operators in a nonorthogonal basis of states which are so important to their studies. In the first half of the thesis, the particle-hole channel is examined to elucidate the effects of collective excitations. Proceeding from a least-action principle, a generalization of the random-phase approximation is developed capable of describing such strongly-interacting Fermi systems as nuclei, nuclear matter, neutron-star matter, and liquid 3 He. A linear response of dynamically correlated system to a weak external perturbation is also derived based on the same framework. In the second half of the thesis, the particle-particle channel is examined to elucidate the effects of pairing in nuclear and neutron-star matter

  3. Reward, interrupted: Inhibitory control and its relevance to addictions.

    Science.gov (United States)

    Jentsch, James David; Pennington, Zachary T

    2014-01-01

    There are broad individual differences in the ability to voluntarily and effortfully suppress motivated, reward-seeking behaviors, and this review presents the hypothesis that these individual differences are relevant to addictive disorders. On one hand, cumulative experience with drug abuse appears to alter the molecular, cellular and circuit mechanisms that mediate inhibitory abilities, leading to increasingly uncontrolled patterns of drug-seeking and -taking. On the other, native inter-individual differences in inhibitory control are apparently a risk factor for aspects of drug-reinforced responding and substance use disorders. In both cases, the behavioral manifestation of poor inhibitory abilities is linked to relatively low striatal dopamine D2-like receptor availability, and evidence is accumulating for a more direct contribution of striatopallidal neurons to cognitive control processes. Mechanistic research is now identifying genes upstream of dopamine transmission that mediate these relationships, as well as the involvement of other neurotransmitter systems, acting alone and in concert with dopamine. The reviewed research stands poised to identify new mechanisms that can be targeted by pharmacotherapies and/or by behavioral interventions that are designed to prevent or treat addictive behaviors and associated behavioral pathology. This article is part of a Special Issue entitled 'NIDA 40th Anniversary Issue'. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. Antigravity: Spin-gravity coupling in action

    Science.gov (United States)

    Plyatsko, Roman; Fenyk, Mykola

    2016-08-01

    The typical motions of a spinning test particle in Schwarzschild's background which show the strong repulsive action of the highly relativistic spin-gravity coupling are considered using the exact Mathisson-Papapetrou equations. An approximated approach to choice solutions of these equations which describe motions of the particle's proper center of mass is developed.

  5. Structural Requirements of Alkylglyceryl-l-Ascorbic Acid Derivatives for Melanogenesis Inhibitory Activity.

    Science.gov (United States)

    Taira, Norihisa; Katsuyama, Yushi; Yoshioka, Masato; Muraoka, Osamu; Morikawa, Toshio

    2018-04-10

    l-Ascorbic acid has multifunctional benefits on skin aesthetics, including inhibition of melanin production, and is widely used in cosmetics. It, however, has low stability and poor skin penetration. We hypothesize that alkylglyceryl-l-ascorbic acid derivatives, highly stable vitamin C-alkylglycerol conjugates, would have similar anti-melanogenic activity with better stability and penetration. We test 28 alkylglyceryl-l-ascorbic acid derivatives ( 1 - 28 ) on theophylline-stimulated B16 melanoma 4A5 cells to determine if they inhibit melanogenesis and establish any structure-function relationships. Although not the most potent inhibitors, 3- O -(2,3-dihydroxypropyl)-2- O -hexyl-l-ascorbic acid ( 6 , IC 50 = 81.4 µM) and 2- O -(2,3-dihydroxypropyl)-3- O -hexyl-l-ascorbic acid ( 20 , IC 50 = 117 µM) are deemed the best candidate derivatives based on their inhibitory activities and low toxicities. These derivatives are also found to be more stable than l-ascorbic acid and to have favorable characteristics for skin penetration. The following structural requirements for inhibitory activity of alkylglyceryl-l-ascorbic acid derivatives are also determined: (i) alkylation of glyceryl-l-ascorbic acid is essential for inhibitory activity; (ii) the 3- O -alkyl-derivatives ( 2 - 14 ) exhibit stronger inhibitory activity than the corresponding 2- O -alkyl-derivatives ( 16 - 28 ); and (iii) derivatives with longer alkyl chains have stronger inhibitory activities. Mechanistically, our studies suggest that l-ascorbic acid derivatives exert their effects by suppressing the mRNA expression of tyrosinase and tyrosine-related protein-1.

  6. Electrophysiological actions of GABAB agonists and antagonists in rat dorso-lateral septal neurones in vitro.

    Science.gov (United States)

    Bon, C; Galvan, M

    1996-06-01

    1. The actions of GABAB-receptor agonists and antagonists on rat dorso-lateral septal neurones in vitro were recorded with intracellular microelectrodes. 2. In the presence of 1 microM tetrodotoxin to prevent indirect neuronal effects caused by action potential-dependent neurotransmitter release, bath application of baclofen (0.1-30 microM) or SK&F 97541 (0.01-3 microM) evoked concentration-dependent hyperpolarizations which reversed close to the potassium equilibrium potential; the EC50S were 0.55 and 0.05 microM, respectively. No significant desensitization was observed during prolonged agonist exposure (dorso-lateral septal nucleus express conventional GABAB receptors, which are involved in the generation of slow inhibitory postsynaptic potentials. CGP 55845A is the most potent GABAB receptor antagonist described in this brain area.

  7. Antiproliferative and apoptotic effects of selective phenolic acids on T47D human breast cancer cells: potential mechanisms of action

    International Nuclear Information System (INIS)

    Kampa, Marilena; Boskou, Dimitrios; Gravanis, Achille; Castanas, Elias; Alexaki, Vassilia-Ismini; Notas, George; Nifli, Artemissia-Phoebe; Nistikaki, Anastassia; Hatzoglou, Anastassia; Bakogeorgou, Efstathia; Kouimtzoglou, Elena; Blekas, George

    2004-01-01

    The oncoprotective role of food-derived polyphenol antioxidants has been described but the implicated mechanisms are not yet clear. In addition to polyphenols, phenolic acids, found at high concentrations in a number of plants, possess antioxidant action. The main phenolic acids found in foods are derivatives of 4-hydroxybenzoic acid and 4-hydroxycinnamic acid. This work concentrates on the antiproliferative action of caffeic acid, syringic acid, sinapic acid, protocatechuic acid, ferulic acid and 3,4-dihydroxy-phenylacetic acid (PAA) on T47D human breast cancer cells, testing their antioxidant activity and a number of possible mechanisms involved (interaction with membrane and intracellular receptors, nitric oxide production). The tested compounds showed a time-dependent and dose-dependent inhibitory effect on cell growth with the following potency: caffeic acid > ferulic acid = protocatechuic acid = PAA > sinapic acid = syringic acid. Caffeic acid and PAA were chosen for further analysis. The antioxidative activity of these phenolic acids in T47D cells does not coincide with their inhibitory effect on tumoral proliferation. No interaction was found with steroid and adrenergic receptors. PAA induced an inhibition of nitric oxide synthase, while caffeic acid competes for binding and results in an inhibition of aryl hydrocarbon receptor-induced CYP1A1 enzyme. Both agents induce apoptosis via the Fas/FasL system. Phenolic acids exert a direct antiproliferative action, evident at low concentrations, comparable with those found in biological fluids after ingestion of foods rich in phenolic acids. Furthermore, the direct interaction with the aryl hydrocarbon receptor, the nitric oxide synthase inhibition and their pro-apoptotic effect provide some insights into their biological mode of action

  8. Inhibitory Interneurons, Oxidative Stress, and Schizophrenia

    OpenAIRE

    Sullivan, Elyse M.; O’Donnell, Patricio

    2012-01-01

    Translational studies are becoming more common in schizophrenia research. The past couple of decades witnessed the emergence of novel ideas regarding schizophrenia pathophysiology that originated from both human and animal studies. The findings that glutamate and gamma-aminobutyric acid transmission are affected in the disease led to the hypothesis of altered inhibitory neurotransmission as critical for cognitive deficits and to an exploration of novel therapeutic approaches aimed at restorin...

  9. Effect of domestic cooking on the starch digestibility, predicted glycemic indices, polyphenol contents and alpha amylase inhibitory properties of beans (Phaseolis vulgaris) and breadfruit (Treculia africana).

    Science.gov (United States)

    Chinedum, E; Sanni, S; Theressa, N; Ebere, A

    2018-01-01

    The effect of processing on starch digestibility, predicted glycemic indices (pGI), polyphenol contents and alpha amylase inhibitory properties of beans (Phaseolis vulgaris) and breadfruit (Treculia africana) was studied. Total starch ranged from 4.3 to 68.3g/100g, digestible starch ranged from 4.3 to 59.2 to 65.7g/100g for the raw and processed legumes; Resistance starch was not detected in most of the legumes except in fried breadfruit and the starches in both the raw and processed breadfruit were more rapidly digested than those from raw and cooked beans. Raw and processed breadfruit had higher hydrolysis curves than raw and processed beans with the amylolysis level in raw breadfruit close to that of white bread. Raw beans had a low glycemic index (GI); boiled beans and breadfruit had intermediate glycemic indices respectively while raw and fried breadfruit had high glycemic indices. Aqueous extracts of the food samples had weak α-amylase inhibition compared to acarbose. The raw and processed legumes contained considerable amounts of dietary phenols and flavonoids. The significant correlation (r=0.626) between α-amylase inhibitory actions of the legumes versus their total phenolic contents suggests the contribution of the phenolic compounds in these legumes to their α-amylase inhibitory properties. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Minimum inhibitory concentration values and problematic disk break ...

    African Journals Online (AJOL)

    Latife Ä°ÅŸeri

    2015-08-08

    Aug 8, 2015 ... to tigecycline, and to test the correlation between the minimal inhibitory concentration (MIC) and ... This study was performed using 108 strains of enterococci. The .... drugs (TetA-E, TetK) from inside the bacterial cell, and ribo-.

  11. Aldose Reductase Inhibitory and Antiglycation Activities of Four ...

    African Journals Online (AJOL)

    Aldose Reductase Inhibitory and Antiglycation Activities of Four Medicinal Plant Standardized Extracts and Their Main Constituents for the Prevention of ... levels in galactosemic condition by using reverse phase high pressure liquid chromatography (RP-HPLC) and gas liquid chromatography (GLC) was determined.

  12. Release of Gentamicin and Vancomycin from Preformed Spacers in Infected Total Hip Arthroplasties: Measurement of Concentrations and Inhibitory Activity in Patients’ Drainage Fluids and Serum

    Directory of Open Access Journals (Sweden)

    Dario Regis

    2013-01-01

    Full Text Available Gentamicin (G and vancomycin (V concentrations in drainage fluids obtained from patients during the first 24 hours after implantation of antibiotic-loaded polymethylmethacrylate (PMMA spacers in two-stage revision of infected total hip arthroplasty were studied. The inhibitory activity of drainage fluids against different multiresistant clinical isolates was investigated as well. Seven hips were treated by implantation of industrial G-loaded spacers. Vancomycin was added by manually mixing with PMMA bone cement. Serum and drainage fluid samples were collected 1, 4, and 24 hours after spacer implantation. Antibiotics concentrations and drains bactericidal titer of combination were determined against multiresistant staphylococcal strains. The release of G and V from PMMA cement at the site of infection was prompt and effective. Serum levels were below the limit of detection. The local release kinetics of G and V from PMMA cement was similar, exerting a pronounced, combined inhibitory effect in the implant site. The inhibitory activity of drainage fluids showed substantial intersubject variability related to antibiotic concentrations and differed according to the pathogens tested. Gentamicin and vancomycin were released from temporary hip spacers at bactericidal concentrations, and their use in combination exerted strong inhibition against methicillin-resistant S. aureus and Coagulase Negative Staphylococci strains.

  13. Inhibitory effects of Citrus hassaku extract and its flavanone glycosides on melanogenesis.

    Science.gov (United States)

    Itoh, Kimihisa; Hirata, Noriko; Masuda, Megumi; Naruto, Shunsuke; Murata, Kazuya; Wakabayashi, Keitaro; Matsuda, Hideaki

    2009-03-01

    The 50% ethanolic extract (CH-ext) obtained from the unripe fruit of Citrus hassaku exhibited significant tyrosinase inhibitory activity. The CH-ext showed antioxidant activity, such as superoxide dismutase (SOD)-like activity and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging activity. Activity-guided fractionation of the CH-ext indicated that flavanone glycoside-rich fractions showed potent tyrosinase inhibitory activity. Further examination revealed that the tyrosinase inhibitory activity and antioxidant activity of the CH-ext were attributable to naringin and neohesperidin, respectively. The CH-ext showed inhibition of melanogenesis without any effects on cell proliferation in cultured murine B16 melanoma cells after glucosamine exposure. The topical application of the CH-ext to the dorsal skin of brownish guinea pigs showed in vivo preventive effects against UVB-induced pigmentation.

  14. Building tolerance by dismantling synapses: inhibitory receptor signaling in natural killer cells.

    Science.gov (United States)

    Huse, Morgan; Catherine Milanoski, S; Abeyweera, Thushara P

    2013-01-01

    Cell surface receptors bearing immunotyrosine-based inhibitory motifs (ITIMs) maintain natural killer (NK) cell tolerance to normal host tissues. These receptors are difficult to analyze mechanistically because they block activating responses in a rapid and comprehensive manner. The advent of high-resolution single cell imaging techniques has enabled investigators to explore the cell biological basis of the inhibitory response. Recent studies using these approaches indicate that ITIM-containing receptors function at least in part by structurally undermining the immunological synapse between the NK cell and its target. In this review, we discuss these new advances and how they might relate to what is known about the biochemistry of inhibitory signaling in NK cells and other cell types. © 2012 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.

  15. Antimicrobial Effects of Psidium Guajava Extract as One Mechanism of its Antidiarrhoeal Action

    Science.gov (United States)

    Lutterodt, G.D.; Ismail, A.; Basheer, R.H.; Baharudin, H. Mohd.

    1999-01-01

    A morphine-like spasmolytic action (not naloxone reversible; involving the inhibition of acetylcholine release) and also effects on the transmural transport of electrolytes (Na+ and K+) and water have been reported as possible modes of the antidiarrhoeal action of polar fractions of Psidium guajava leaf extractives. The objective for this study was to verify if the reported modes of the antidiarrhoeal action should be broadened to include direct antimicrobial actions on some of the more common bacteria known to cause toxin-induced acute diarrhoea. Serial dilutions of a water-soluble, freeze-dried methanolic extract were tested on 10 such organisms, grown separately on nutrient agar plates, to determine the minimum inhibitory concentration (MIC) for each of these bacteria. These included the causative agents for (i) enteric fever (Salmonella typhi, Salmonella paratyphi A, Salmonella paratyphi B and Salmonella paratyphi C), (ii) food poisoning (Salmonella typhimurium and Staphylococcus aureus), (iii) dysentery (Shigella dysenteriae, Shigella flexneri and Shigella sonnei), and (iv) cholera (Vibrio cholerae). The growth of all these organisms was inhibited at the MIC of 10mg/ml of the extract, which is equivalent to 2.5μg/ml of active extractable flavonoids. The most sensitive organisms (MIC = 1mg/ml) were Staphylococcus aureus, Vibrio cholerae and Shigella flexneri. PMID:22589684

  16. Inhibitory control in young children and its role in emerging internalization.

    Science.gov (United States)

    Kochanska, G; Murray, K; Jacques, T Y; Koenig, A L; Vandegeest, K A

    1996-04-01

    We examined inhibitory control as a quality of temperament that contributes to internalization. Children were assessed twice, at 26-41 months (N = 103) and at 43-56 months (N = 99), on repeated occasions, in multiple observational contexts and using parental reports. Comprehensive behavioral batteries incorporating multiple tasks were designed to measure inhibitory control at toddler and preschool age. They had good internal consistencies, corresponded with maternal ratings, and were developmentally sensitive. Individual children's performance was significantly correlated across both assessments, indicating stable individual differences. Girls surpassed boys at both ages. Children's internalization was observed while they were alone with prohibited objects, with a mundane chore, playing games that occasioned cheating, being induced to violate standards of conduct, and assessed using maternal reports. Inhibitory control was significantly associated with internalization, both contemporaneously and as a predictor in the longitudinal sense. The implications for considering children's temperament as a significant, yet often neglected contributor to developing internalization are discussed.

  17. Your actions in my cerebellum: subclinical deficits in action observation in patients with unilateral chronic cerebellar stroke.

    Science.gov (United States)

    Cattaneo, Luigi; Fasanelli, Monica; Andreatta, Olaf; Bonifati, Domenico Marco; Barchiesi, Guido; Caruana, Fausto

    2012-03-01

    Empirical evidence indicates that cognitive consequences of cerebellar lesions tend to be mild and less important than the symptoms due to lesions to cerebral areas. By contrast, imaging studies consistently report strong cerebellar activity during tasks of action observation and action understanding. This has been interpreted as part of the automatic motor simulation process that takes place in the context of action observation. The function of the cerebellum as a sequencer during executed movements makes it a good candidate, within the framework of embodied cognition, for a pivotal role in understanding the timing of action sequences. Here, we investigated a cohort of eight patients with chronic, first-ever, isolated, ischemic lesions of the cerebellum. The experimental task consisted in identifying a plausible sequence of pictures from a randomly ordered group of still frames extracted from (a) a complex action performed by a human actor ("biological action" test) or (b) a complex physical event occurring to an inanimate object ("folk physics" test). A group of 16 healthy participants was used as control. The main result showed that cerebellar patients performed significantly worse than controls in both sequencing tasks, but performed much worse in the "biological action" test than in the "folk physics" test. The dissociation described here suggests that observed sequences of simple motor acts seem to be represented differentially from other sequences in the cerebellum.

  18. An Inhibitory Motif on the 5’UTR of Several Rotavirus Genome Segments Affects Protein Expression and Reverse Genetics Strategies

    Science.gov (United States)

    Papa, Guido; Eichwald, Catherine; Burrone, Oscar R.

    2016-01-01

    Rotavirus genome consists of eleven segments of dsRNA, each encoding one single protein. Viral mRNAs contain an open reading frame (ORF) flanked by relatively short untranslated regions (UTRs), whose role in the viral cycle remains elusive. Here we investigated the role of 5’UTRs in T7 polymerase-driven cDNAs expression in uninfected cells. The 5’UTRs of eight genome segments (gs3, gs5-6, gs7-11) of the simian SA11 strain showed a strong inhibitory effect on the expression of viral proteins. Decreased protein expression was due to both compromised transcription and translation and was independent of the ORF and the 3’UTR sequences. Analysis of several mutants of the 21-nucleotide long 5’UTR of gs 11 defined an inhibitory motif (IM) represented by its primary sequence rather than its secondary structure. IM was mapped to the 5’ terminal 6-nucleotide long pyrimidine-rich tract 5’-GGY(U/A)UY-3’. The 5’ terminal position within the mRNA was shown to be essentially required, as inhibitory activity was lost when IM was moved to an internal position. We identified two mutations (insertion of a G upstream the 5’UTR and the U to A mutation of the fifth nucleotide of IM) that render IM non-functional and increase the transcription and translation rate to levels that could considerably improve the efficiency of virus helper-free reverse genetics strategies. PMID:27846320

  19. Bodily action penetrates affective perception

    Science.gov (United States)

    Rigutti, Sara; Gerbino, Walter

    2016-01-01

    Fantoni & Gerbino (2014) showed that subtle postural shifts associated with reaching can have a strong hedonic impact and affect how actors experience facial expressions of emotion. Using a novel Motor Action Mood Induction Procedure (MAMIP), they found consistent congruency effects in participants who performed a facial emotion identification task after a sequence of visually-guided reaches: a face perceived as neutral in a baseline condition appeared slightly happy after comfortable actions and slightly angry after uncomfortable actions. However, skeptics about the penetrability of perception (Zeimbekis & Raftopoulos, 2015) would consider such evidence insufficient to demonstrate that observer’s internal states induced by action comfort/discomfort affect perception in a top-down fashion. The action-modulated mood might have produced a back-end memory effect capable of affecting post-perceptual and decision processing, but not front-end perception. Here, we present evidence that performing a facial emotion detection (not identification) task after MAMIP exhibits systematic mood-congruent sensitivity changes, rather than response bias changes attributable to cognitive set shifts; i.e., we show that observer’s internal states induced by bodily action can modulate affective perception. The detection threshold for happiness was lower after fifty comfortable than uncomfortable reaches; while the detection threshold for anger was lower after fifty uncomfortable than comfortable reaches. Action valence induced an overall sensitivity improvement in detecting subtle variations of congruent facial expressions (happiness after positive comfortable actions, anger after negative uncomfortable actions), in the absence of significant response bias shifts. Notably, both comfortable and uncomfortable reaches impact sensitivity in an approximately symmetric way relative to a baseline inaction condition. All of these constitute compelling evidence of a genuine top-down effect on

  20. Bodily action penetrates affective perception

    Directory of Open Access Journals (Sweden)

    Carlo Fantoni

    2016-02-01

    Full Text Available Fantoni & Gerbino (2014 showed that subtle postural shifts associated with reaching can have a strong hedonic impact and affect how actors experience facial expressions of emotion. Using a novel Motor Action Mood Induction Procedure (MAMIP, they found consistent congruency effects in participants who performed a facial emotion identification task after a sequence of visually-guided reaches: a face perceived as neutral in a baseline condition appeared slightly happy after comfortable actions and slightly angry after uncomfortable actions. However, skeptics about the penetrability of perception (Zeimbekis & Raftopoulos, 2015 would consider such evidence insufficient to demonstrate that observer’s internal states induced by action comfort/discomfort affect perception in a top-down fashion. The action-modulated mood might have produced a back-end memory effect capable of affecting post-perceptual and decision processing, but not front-end perception. Here, we present evidence that performing a facial emotion detection (not identification task after MAMIP exhibits systematic mood-congruent sensitivity changes, rather than response bias changes attributable to cognitive set shifts; i.e., we show that observer’s internal states induced by bodily action can modulate affective perception. The detection threshold for happiness was lower after fifty comfortable than uncomfortable reaches; while the detection threshold for anger was lower after fifty uncomfortable than comfortable reaches. Action valence induced an overall sensitivity improvement in detecting subtle variations of congruent facial expressions (happiness after positive comfortable actions, anger after negative uncomfortable actions, in the absence of significant response bias shifts. Notably, both comfortable and uncomfortable reaches impact sensitivity in an approximately symmetric way relative to a baseline inaction condition. All of these constitute compelling evidence of a genuine top

  1. Intraindividual variability in inhibitory function in adults with ADHD--an ex-Gaussian approach.

    Directory of Open Access Journals (Sweden)

    Dennis Gmehlin

    Full Text Available OBJECTIVE: Attention deficit disorder (ADHD is commonly associated with inhibitory dysfunction contributing to typical behavioral symptoms like impulsivity or hyperactivity. However, some studies analyzing intraindividual variability (IIV of reaction times in children with ADHD (cADHD question a predominance of inhibitory deficits. IIV is a measure of the stability of information processing and provides evidence that longer reaction times (RT in inhibitory tasks in cADHD are due to only a few prolonged responses which may indicate deficits in sustained attention rather than inhibitory dysfunction. We wanted to find out, whether a slowing in inhibitory functioning in adults with ADHD (aADHD is due to isolated slow responses. METHODS: Computing classical RT measures (mean RT, SD, ex-Gaussian parameters of IIV (which allow a better separation of reaction time (mu, variability (sigma and abnormally slow responses (tau than classical measures as well as errors of omission and commission, we examined response inhibition in a well-established GoNogo task in a sample of aADHD subjects without medication and healthy controls matched for age, gender and education. RESULTS: We did not find higher numbers of commission errors in aADHD, while the number of omissions was significantly increased compared with controls. In contrast to increased mean RT, the distributional parameter mu did not document a significant slowing in aADHD. However, subjects with aADHD were characterized by increased IIV throughout the entire RT distribution as indicated by the parameters sigma and tau as well as the SD of reaction time. Moreover, we found a significant correlation between tau and the number of omission errors. CONCLUSIONS: Our findings question a primacy of inhibitory deficits in aADHD and provide evidence for attentional dysfunction. The present findings may have theoretical implications for etiological models of ADHD as well as more practical implications for

  2. Effective action calculation in lattice QCD

    International Nuclear Information System (INIS)

    Hoek, J.

    1983-01-01

    A method (called the effective action method) devised to make analytic calculations in Quantum Chromodynamics in the region of strong coupling is presented. First, the author deals with developing the calculation of a strong coupling expansion of the generating functional for gauge systems on a lattice with arbitrary sources. An accompanying manual describes the implementation of this calculation on a computer. The next step consists of substituting the expressions for the one-link free energies for a specific gauge group in the result of the previous calculation. This process of substitution, together with the replacement of the sources by a bilinear combination of fermion fields, is described for the group SU(3). More details on the implementation of the substitution scheme on a computer can be found in the accompanying manual. From the effective action thus obtained in terms of meson fields and baryon fields the Green functions of the theory can be derived. As an illustrative application the effective potential determining the vacuum expectation value of the meson field is calculated. (Auth.)

  3. Spikes matter for phase-locked bursting in inhibitory neurons

    Science.gov (United States)

    Jalil, Sajiya; Belykh, Igor; Shilnikov, Andrey

    2012-03-01

    We show that inhibitory networks composed of two endogenously bursting neurons can robustly display several coexistent phase-locked states in addition to stable antiphase and in-phase bursting. This work complements and enhances our recent result [Jalil, Belykh, and Shilnikov, Phys. Rev. EPLEEE81539-375510.1103/PhysRevE.81.045201 81, 045201(R) (2010)] that fast reciprocal inhibition can synchronize bursting neurons due to spike interactions. We reveal the role of spikes in generating multiple phase-locked states and demonstrate that this multistability is generic by analyzing diverse models of bursting networks with various fast inhibitory synapses; the individual cell models include the reduced leech heart interneuron, the Sherman model for pancreatic beta cells, and the Purkinje neuron model.

  4. Identification of novel dipeptidyl peptidase IV (DPP-IV) inhibitory peptides in camel milk protein hydrolysates.

    Science.gov (United States)

    Nongonierma, Alice B; Paolella, Sara; Mudgil, Priti; Maqsood, Sajid; FitzGerald, Richard J

    2018-04-01

    Nine novel dipeptidyl peptidase IV (DPP-IV) inhibitory peptides (FLQY, FQLGASPY, ILDKEGIDY, ILELA, LLQLEAIR, LPVP, LQALHQGQIV, MPVQA and SPVVPF) were identified in camel milk proteins hydrolysed with trypsin. This was achieved using a sequential approach combining liquid chromatography tandem mass spectrometry (LC-MS/MS), qualitative/quantitative structure activity relationship (QSAR) and confirmatory studies with synthetic peptides. The most potent camel milk protein-derived DPP-IV inhibitory peptides, LPVP and MPVQA, had DPP-IV half maximal inhibitory concentrations (IC 50 ) of 87.0 ± 3.2 and 93.3 ± 8.0 µM, respectively. DPP-IV inhibitory peptide sequences identified within camel and bovine milk protein hydrolysates generated under the same hydrolysis conditions differ. This was linked to differences in enzyme selectivity for peptide bond cleavage of camel and bovine milk proteins as well as dissimilarities in their amino acid sequences. Camel milk proteins contain novel DPP-IV inhibitory peptides which may play a role in the regulation of glycaemia in humans. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Selective deficiencies in descending inhibitory modulation in neuropathic rats: implications for enhancing noradrenergic tone.

    Science.gov (United States)

    Patel, Ryan; Qu, Chaoling; Xie, Jennifer Y; Porreca, Frank; Dickenson, Anthony H

    2018-05-31

    Pontine noradrenergic neurones form part of a descending inhibitory system that influences spinal nociceptive processing. Weak or absent descending inhibition is a common feature of chronic pain patients. We examined the extent to which the descending noradrenergic system is tonically active, how control of spinal neuronal excitability is integrated into thalamic relays within sensory-discriminative projection pathways, and how this inhibitory control is altered after nerve injury. In vivo electrophysiology was performed in anaesthetised spinal nerve ligated (SNL) and sham-operated rats to record from wide dynamic range neurones in the ventral posterolateral thalamus (VPL). In sham rats, spinal block of α2-adrenoceptors with atipamezole resulted in enhanced stimulus-evoked and spontaneous firing in the VPL, and produced conditioned place avoidance. However, in SNL rats these conditioned avoidance behaviours were absent. Furthermore, inhibitory control of evoked neuronal responses was lost but spinal atipamezole markedly increased spontaneous firing. Augmenting spinal noradrenergic tone in neuropathic rats with reboxetine, a selective noradrenergic reuptake inhibitor, modestly reinstated inhibitory control of evoked responses in the VPL but had no effect on spontaneous firing. In contrast, clonidine, an α2 agonist, inhibited both evoked and spontaneous firing, and exhibited increased potency in SNL rats compared to sham controls. These data suggest descending noradrenergic inhibitory pathways are tonically active in sham rats. Moreover, in neuropathic states descending inhibitory control is diminished, but not completely absent, and distinguishes between spontaneous and evoked neuronal activity. These observations may have implications for how analgesics targeting the noradrenergic system provide relief.

  6. D-sorbose inhibits disaccharidase activity and demonstrates suppressive action on postprandial blood levels of glucose and insulin in the rat.

    Science.gov (United States)

    Oku, Tsuneyuki; Murata-Takenoshita, Yoko; Yamazaki, Yuko; Shimura, Fumio; Nakamura, Sadako

    2014-11-01

    In an attempt to develop D-sorbose as a new sweetener that could help in preventing lifestyle-related diseases, we investigated the inhibitory effect of D-sorbose on disaccharidase activity, using the brush border membrane vesicles of rat small intestines. The inhibitory effect was compared with that of L-sorbose and other rare sugars, and the small intestinal disaccharidases in rats was compared with that of humans as well. In humans and the small intestines of rats, d-sorbose strongly inhibited sucrase activity and weakly inhibited maltase activity. Inhibition by D-sorbose of sucrase activity was similar to that of L-arabinose, and the K(i) of D-sorbose was 7.5 mM. Inhibition by D-sorbose was very strong in comparison with that of L-sorbose (K(i), 60.8 mM), whereas inhibition of d-tagatose was between that of D-sorbose and L-sorbose. The inhibitory mode of D-sorbose for sucrose and maltase was uncompetitive, and that of L-sorbose was competitive. To determine a suppressive effect on postprandial blood levels of glucose and insulin via inhibition of sucrase activity, sucrose solution with or without D-sorbose was administered to rats. Increments in the blood levels of glucose and insulin were suppressed significantly after administration of sucrose solution with D-sorbose to rats, in comparison to administration of sucrose solution without D-sorbose. In contrast, the suppressive effect of L-sorbose on postprandial blood levels of glucose and insulin was very weak. These results suggest that D-sorbose may have an inhibitory effect on disaccharidase activity and could be used as a sweetener to suppress the postprandial elevation of blood levels of glucose and insulin. The use of D-sorbose as a sweetener may contribute to the prevention of lifestyle-related diseases, such as type 2 diabetes mellitus. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Macrophage inhibitory cytokine-1 (MIC-1/GDF15 slows cancer development but increases metastases in TRAMP prostate cancer prone mice.

    Directory of Open Access Journals (Sweden)

    Yasmin Husaini

    Full Text Available Macrophage inhibitory cytokine-1 (MIC-1/GDF15, a divergent member of the TGF-β superfamily, is over-expressed by many common cancers including those of the prostate (PCa and its expression is linked to cancer outcome. We have evaluated the effect of MIC-1/GDF15 overexpression on PCa development and spread in the TRAMP transgenic model of spontaneous prostate cancer. TRAMP mice were crossed with MIC-1/GDF15 overexpressing mice (MIC-1(fms to produce syngeneic TRAMP(fmsmic-1 mice. Survival rate, prostate tumor size, histopathological grades and extent of distant organ metastases were compared. Metastasis of TC1-T5, an androgen independent TRAMP cell line that lacks MIC-1/GDF15 expression, was compared by injecting intravenously into MIC-1(fms and syngeneic C57BL/6 mice. Whilst TRAMP(fmsmic-1 survived on average 7.4 weeks longer, had significantly smaller genitourinary (GU tumors and lower PCa histopathological grades than TRAMP mice, more of these mice developed distant organ metastases. Additionally, a higher number of TC1-T5 lung tumor colonies were observed in MIC-1(fms mice than syngeneic WT C57BL/6 mice. Our studies strongly suggest that MIC-1/GDF15 has complex actions on tumor behavior: it limits local tumor growth but may with advancing disease, promote metastases. As MIC-1/GDF15 is induced by all cancer treatments and metastasis is the major cause of cancer treatment failure and cancer deaths, these results, if applicable to humans, may have a direct impact on patient care.

  8. Inhibitory Activities of Antioxidant Flavonoids from Tamarix gallica on Amyloid Aggregation Related to Alzheimer's and Type 2 Diabetes Diseases.

    Science.gov (United States)

    Ben Hmidene, Asma; Hanaki, Mizuho; Murakami, Kazuma; Irie, Kazuhiro; Isoda, Hiroko; Shigemori, Hideyuki

    2017-01-01

    The prevention of amyloid aggregation is promising for the treatment of age-related diseases such as Alzheimer's (AD) and type 2 diabetes (T2D). Ten antioxidant flavonoids isolated from the medicinal halophyte Tamarix gallica were tested for their amyloid aggregation inhibition potential. Glucuronosylated flavonoids show relatively strong inhibitory activity of Amyloid β (Aβ) and human islet amyloid polypeptide (hIAPP) aggregation compared to their aglycone analogs. Structure-activity relationship of the flavonoids suggests that the catechol moiety is important for amyloid aggregation inhibition, while the methylation of the carboxyl group in the glucuronide moiety and of the hydroxyl group in the aglycone flavonoids decreased it.

  9. Expression of macrophage migration inhibitory factor in footpad skin lesions with diabetic neuropathy.

    Science.gov (United States)

    Up Noh, Sun; Lee, Won-Young; Kim, Won-Serk; Lee, Yong-Taek; Jae Yoon, Kyung

    2018-01-01

    Background Diabetic neuropathy originating in distal lower extremities is associated with pain early in the disease course, overwhelming in the feet. However, the pathogenesis of diabetic neuropathy remains unclear. Macrophage migration inhibitory factor has been implicated in the onset of neuropathic pain and the development of diabetes. Objective of this study was to observe pain syndromes elicited in the footpad of diabetic neuropathy rat model and to assess the contributory role of migration inhibitory factor in the pathogenesis of diabetic neuropathy. Methods Diabetic neuropathy was made in Sprague Dawley rats by streptozotocin. Pain threshold was evaluated using von Frey monofilaments for 24 weeks. On comparable experiment time after streptozotocin injection, all footpads were prepared for following procedures; glutathione assay, terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling staining, immunohistochemistry staining, real-time reverse transcription polymerase chain reaction, and Western blot. Additionally, human HaCaT skin keratinocytes were treated with methylglyoxal, transfected with migration inhibitory factor/control small interfering RNA, and prepared for real-time reverse transcription polymerase chain reaction and Western blot. Results As compared to sham group, pain threshold was significantly reduced in diabetic neuropathy group, and glutathione was decreased in footpad skin, simultaneously, cell death was increased. Over-expression of migration inhibitory factor, accompanied by low expression of glyoxalase-I and intraepidermal nerve fibers, was shown on the footpad skin lesions of diabetic neuropathy. But, there was no significance in expression of neurotransmitters and inflammatory mediators such as transient receptor potential vanilloid 1, mas-related G protein coupled receptor D, nuclear factor kappa B, tumor necrosis factor-alpha, and interleukin-6 between diabetic neuropathy group and sham group. Intriguingly

  10. Cardiac Gene Expression Knockdown Using Small Inhibitory RNA-Loaded Microbubbles and Ultrasound.

    Directory of Open Access Journals (Sweden)

    Jonathan A Kopechek

    Full Text Available RNA interference has potential therapeutic value for cardiac disease, but targeted delivery of interfering RNA is a challenge. Custom designed microbubbles, in conjunction with ultrasound, can deliver small inhibitory RNA to target tissues in vivo. The efficacy of cardiac RNA interference using a microbubble-ultrasound theranostic platform has not been demonstrated in vivo. Therefore, our objective was to test the hypothesis that custom designed microbubbles and ultrasound can mediate effective delivery of small inhibitory RNA to the heart. Microbubble and ultrasound mediated cardiac RNA interference was tested in transgenic mice displaying cardiac-restricted luciferase expression. Luciferase expression was assayed in select tissues of untreated mice (n = 14. Mice received intravenous infusion of cationic microbubbles bearing small inhibitory RNA directed against luciferase (n = 9 or control RNA (n = 8 during intermittent cardiac-directed ultrasound at mechanical index of 1.6. Simultaneous echocardiography in a separate group of mice (n = 3 confirmed microbubble destruction and replenishment during treatment. Three days post treatment, cardiac luciferase messenger RNA and protein levels were significantly lower in ultrasound-treated mice receiving microbubbles loaded with small inhibitory RNA directed against luciferase compared to mice receiving microbubbles bearing control RNA (23±7% and 33±7% of control mice, p<0.01 and p = 0.03, respectively. Passive cavitation detection focused on the heart confirmed that insonification resulted in inertial cavitation. In conclusion, small inhibitory RNA-loaded microbubbles and ultrasound directed at the heart significantly reduced the expression of a reporter gene. Ultrasound-targeted destruction of RNA-loaded microbubbles may be an effective image-guided strategy for therapeutic RNA interference in cardiac disease.

  11. Effect of in vitro irradiation and cell cycle-inhibitory drugs on the spontaneous human IgE synthesis in vitro

    International Nuclear Information System (INIS)

    Del Prete, G.F.; Vercelli, D.; Tiri, A.; Maggi, E.; Rossi, O.; Romagnani, S.; Ricci, M.

    1987-01-01

    The in vitro effects of radiation, diterpine forskolin (FK), and hydrocortisone (HC) on the in vitro spontaneous IgE synthesis by peripheral blood B-lymphocytes from atopic patients were investigated. Without affecting cell viability, in vitro irradiation inhibited in a dose-dependent fashion de novo IgE synthesis in vitro by B cells from all patients examined with a mean 40% reduction of in vitro IgE product after treatment with 100 rads. In contrast, the in vitro IgE production by the U266 myeloma cell line was unaffected, even by irradiation with 1600 rads. The addition to B cell cultures from atopic patients of FK consistently resulted in a dose-dependent inhibition of the spontaneous IgE production in vitro. The addition to cultures of 10(-5) and 10(-6) molar concentrations of HC was also usually inhibitory, whereas lower HC concentrations were uneffective or even enhanced the spontaneous in vitro IgE synthesis. When 10(-6) molar concentrations of both HC and FK were combined in culture, a summation inhibitory effect on the spontaneous IgE synthesis was observed. In contrast, neither FK nor HC had inhibitory effect on the in vitro spontaneous IgE synthesis by the U266 myeloma cell line. The spontaneous in vitro IgE synthesis by B cells from patients with Hodgkin's disease, demonstrating high levels of serum IgE, was strongly reduced or virtually abolished after patients underwent total nodal irradiation to prevent the spread of the disease. In addition, the in vitro spontaneous IgE synthesis by B cells from atopic patients was markedly decreased or abolished by in vivo administration of betamethasone

  12. Inhibitory Effects of Daiokanzoto (Da-Huang-Gan-Cao-Tang on P-Glycoprotein

    Directory of Open Access Journals (Sweden)

    Yuka Watanabe

    2012-01-01

    Full Text Available We have studied the effects of various Kampo medicines on P-glycoprotein (P-gp, a drug transporter, in vitro. The present study focused on Daiokanzoto (Da-Huang-Gan-Cao-Tang, which shows the most potent inhibitory effects on P-gp among the 50 Kampo medicines studied, and investigated the P-gp inhibitory effects of Daiokanzoto herbal ingredients (rhubarb and licorice root and their components by an ATPase assay using human P-gp membrane. Both rhubarb and licorice root significantly inhibited ATPase activity, and the effects of rhubarb were more potent than those of licorice root. The content of rhubarb in Daiokanzoto is double that in licorice root, and the inhibition patterns of Daiokanzoto and rhubarb involve both competitive and noncompetitive inhibition, suggesting that the inhibitory effects of Daiokanzoto are mainly due to rhubarb. Concerning the components of rhubarb, concentration-dependent inhibitory effects were observed for (−-catechin gallate, (−-epicatechin gallate, and (−-epigallocatechin gallate. In conclusion, rhubarb may cause changes in the drug dispositions of P-gp substrates through the inhibition of P-gp. It appears that attention should be given to the interactions between these drugs and Kampo medicines containing rhubarb as an herbal ingredient.

  13. Differences in Inhibitory Control between Impulsive and Premeditated Aggression in Juvenile Inmates

    Directory of Open Access Journals (Sweden)

    Zhuo Zhang

    2017-07-01

    Full Text Available Inhibitory control dysfunction was considered a universal characteristic of violent offenders. The aim of this study was to examine differences in inhibitory control between two subtypes of violent youth; those displaying predominantly impulsive and those presenting predominantly premeditated aggression (PM. Forty-four juvenile offenders, defined on the basis of the Procedures for the Classification of Aggressive/Violent Acts (Stanford and Barratt, 2001 participated (N = 23: impulsive; N = 21 premeditated. A visual Go/NoGo task was used to compare behavioral responses and event-related potentials (ERPs between groups. The task contained two letters (W and M, W was the Go stimulus and M the NoGo stimulus. The impulsive youth showed a significantly greater decrease in N2 latency for Go relative to NoGo trials than the premeditated aggressive youth. The differentiation in N2 amplitude between Go and NoGo (N2d was negatively correlated with impulsivity of aggression. Both groups showed no significant central NoGo P3. Our findings suggest that impulsive violent youth show stronger prepotent responses and impaired conflict monitoring during early inhibitory control processing relative to premeditated aggressive youth. Both impulsive and premeditated violent youth may show impaired response inhibition at the late processing stage of inhibitory control.

  14. Enzyme inhibitory and radical scavenging effects of some antidiabetic plants of Turkey

    Science.gov (United States)

    Orhan, Nilüfer; Hoçbaç, Sanem; Orhan, Didem Deliorman; Asian, Mustafa; Ergun, Fatma

    2014-01-01

    Objective(s): Ethnopharmacological field surveys demonstrated that many plants, such as Gentiana olivieri, Helichrysum graveolens, Helichrysum plicatum ssp. plicatum, Juniperus oxycedrus ssp. oxycedrus, Juniperus communis var. saxatilis, Viscum album (ssp. album, ssp. austriacum), are used as traditional medicine for diabetes in different regions of Anatolia. The present study was designed to evaluate the in vitro antidiabetic effects of some selected plants, tested in animal models recently. Materials and Methods: α-glucosidase and α-amylase enzyme inhibitory effects of the plant extracts were investigated and Acarbose was used as a reference drug. Additionally, radical scavenging capacities were determined using 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) ABTS radical cation scavenging assay and total phenolic content of the extracts were evaluated using Folin Ciocalteu method. Results: H. graveolens ethanol extract exhibited the highest inhibitory activity (55.7 % ± 2.2) on α-amylase enzyme. Additionally, J. oxycedrus hydro-alcoholic leaf extract had potent α-amylase inhibitory effect, while the hydro-alcoholic extract of J. communis fruit showed the highest α-glucosidase inhibitory activity (IC50: 4.4 μg/ml). Conclusion: Results indicated that, antidiabetic effect of hydro-alcoholic extracts of H. graveolens capitulums, J. communis fruit and J. oxycedrus leaf might arise from inhibition of digestive enzymes. PMID:25140204

  15. Enzyme inhibitory and radical scavenging effects of some antidiabetic plants of Turkey

    Directory of Open Access Journals (Sweden)

    Nilüfer Orhan

    2014-06-01

    Full Text Available Objective(s:Ethnopharmacological field surveys demonstrated that many plants, such as Gentiana olivieri, Helichrysum graveolens, Helichrysum plicatum ssp. plicatum, Juniperus oxycedrus ssp. oxycedrus, Juniperus  communis var. saxatilis, Viscum album (ssp. album, ssp. austriacum, are used as traditional medicine for diabetes in different regions of Anatolia. The present study was designed to evaluate the in vitro antidiabetic effects of some selected plants, tested in animal models recently. Materials and Methods: α-glucosidase and α-amylase enzyme inhibitory effects of the plant extracts were investigated and Acarbose was used as a reference drug. Additionally, radical scavenging capacities were determined using 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid ABTS radical cation scavenging assay and total phenolic content of the extracts were evaluated using Folin Ciocalteu method. Results: H. graveolens ethanol extract exhibited the highest inhibitory activity (55.7 % ± 2.2 on α-amylase enzyme. Additionally, J. oxycedrus hydro-alcoholic leaf extract had potent α-amylase inhibitory effect, while the hydro-alcoholic extract of J. communis fruit showed the highest α-glucosidase inhibitory activity (IC50: 4.4 μg/ml. Conclusion:Results indicated that, antidiabetic effect of hydro-alcoholic extracts of H. graveolens capitulums, J. communis fruit and J. oxycedrus leaf might arise from inhibition of digestive enzymes.

  16. Interaction of a strong vortex with decaying turbulence

    International Nuclear Information System (INIS)

    Terry, P.W.

    1988-01-01

    The evolution of a localized, axially symmetric vortex under the action of shear stresses associated with decaying two-dimensional turbulent vorticity which is inhomogeneous in the presence of the vortex is studied analytically. For a vortex which is sufficiently strong relative to the coefficient of turbulent eddy viscosity, it is shown that turbulent fluctuations in the vortex interior and diffusion of coherent vorticity by the turbulence localize to the vortex periphery. It is also found that the coefficient of diffusion is small compared to the coefficient of eddy viscosity. 8 refs

  17. Increased beta rhythm as an indicator of inhibitory mechanisms in tourette syndrome.

    Science.gov (United States)

    Niccolai, Valentina; van Dijk, Hanneke; Franzkowiak, Stephanie; Finis, Jennifer; Südmeyer, Martin; Jonas, Melanie; Thomalla, Götz; Siebner, Hartwig Roman; Müller-Vahl, Kirsten; Münchau, Alexander; Schnitzler, Alfons; Biermann-Ruben, Katja

    2016-03-01

    Inhibitory oscillatory mechanisms subserving tic compensation have been put forward in Tourette syndrome. Modulation of the beta rhythm (15-25 Hz) as the well-established oscillatory movement execution-inhibition indicator was tested during a cognitive-motor task in patients with Tourette syndrome. Performing a Go/NoGo task, 12 patients with Tourette syndrome and 12 matched controls were recorded using whole-head magnetoencephalography. Compared to healthy participants, patients showed less beta suppression in the sensorimotor area and enhanced beta power in parieto-occipital brain regions contralaterally to the response hand. Average beta power and power gain correlated negatively with tic severity. Increased motor inhibitory as well as visuomotor attentional processes are likely to subserve tic compensation. Correlational results suggest that stronger inhibitory compensation accompanies less tic severity. © 2016 International Parkinson and Movement Disorder Society.

  18. Optimization of Approximate Inhibitory Rules Relative to Number of Misclassifications

    KAUST Repository

    Alsolami, Fawaz

    2013-10-04

    In this work, we consider so-called nonredundant inhibitory rules, containing an expression “attribute:F value” on the right- hand side, for which the number of misclassifications is at most a threshold γ. We study a dynamic programming approach for description of the considered set of rules. This approach allows also the optimization of nonredundant inhibitory rules relative to the length and coverage. The aim of this paper is to investigate an additional possibility of optimization relative to the number of misclassifications. The results of experiments with decision tables from the UCI Machine Learning Repository show this additional optimization achieves a fewer misclassifications. Thus, the proposed optimization procedure is promising.

  19. Tyrosinase inhibitory components from Aloe vera and their antiviral activity.

    Science.gov (United States)

    Kim, Jang Hoon; Yoon, Ju-Yeon; Yang, Seo Young; Choi, Seung-Kook; Kwon, Sun Jung; Cho, In Sook; Jeong, Min Hee; Ho Kim, Young; Choi, Gug Seoun

    2017-12-01

    A new compound, 9-dihydroxyl-2'-O-(Z)-cinnamoyl-7-methoxy-aloesin (1), and eight known compounds (2-9) were isolated from Aloe vera. Their structures were elucidated using 1D/2D nuclear magnetic resonance and mass spectra. Compound 9 exhibited reversible competitive inhibitory activity against the enzyme tyrosinase, with an IC 50 value of 9.8 ± 0.9 µM. A molecular simulation revealed that compound 9 interacts via hydrogen bonding with residues His244, Thr261, and Val283 of tyrosinase. Additionally, compounds 3 and 7 were shown by half-leaf assays to exhibit inhibitory activity towards Pepper mild mottle virus.

  20. Contending logics of action in development cooperation

    DEFF Research Database (Denmark)

    Fejerskov, Adam Moe

    2017-01-01

    and organizational change. This article builds an analytical framework for empirically exploring logics of action in development cooperation and then explores a case of how two strong logics, those of ‘cost-effectiveness’ and ‘gender equality and women’s empowerment’, respectively, contend in the Bill and Melinda...

  1. KATP channels in the nodose ganglia mediate the orexigenic actions of ghrelin

    Science.gov (United States)

    Grabauskas, Gintautas; Wu, Xiaoyin; Lu, Yuanxu; Heldsinger, Andrea; Song, Il; Zhou, Shi-Yi; Owyang, Chung

    2015-01-01

    Abstract Ghrelin is the only known hunger signal derived from the peripheral tissues. Ghrelin overcomes the satiety signals evoked by anorexigenic molecules, such as cholecystokinin (CCK) and leptin, to stimulate feeding. The mechanisms by which ghrelin reduces the sensory signals evoked by anorexigenic hormones, which act via the vagus nerve to stimulate feeding, are unknown. Patch clamp recordings of isolated rat vagal neurons show that ghrelin hyperpolarizes neurons by activating K+ conductance. Administering a KATP channel antagonist or silencing Kir6.2, a major subunit of the KATP channel, abolished ghrelin inhibition in vitro and in vivo. Patch clamp studies show that ghrelin inhibits currents evoked by leptin and CCK-8, which operate through independent ionic channels. The inhibitory actions of ghrelin were abolished by treating the vagal ganglia neurons with pertussis toxin, as well as phosphatidylinositol 3-kinase (PI3K) or extracellular signal-regulated kinase 1 and 2 (Erk1/2) small interfering RNA. In vivo gene silencing of PI3K and Erk1/2 in the nodose ganglia prevented ghrelin inhibition of leptin- or CCK-8-evoked vagal firing. Feeding experiments showed that silencing Kir6.2 in the vagal ganglia abolished the orexigenic actions of ghrelin. These data indicate that ghrelin modulates vagal ganglia neuron excitability by activating KATP conductance via the growth hormone secretagogue receptor subtype 1a–Gαi–PI3K–Erk1/2–KATP pathway. The resulting hyperpolarization renders the neurons less responsive to signals evoked by anorexigenic hormones. This provides a mechanism to explain the actions of ghrelin with respect to overcoming anorexigenic signals that act via the vagal afferent pathways. Key points Ghrelin, a hunger signalling peptide derived from the peripheral tissues, overcomes the satiety signals evoked by anorexigenic molecules, such as cholecystokinin (CCK) and leptin, to stimulate feeding. Using in vivo and in vitro electrophysiological

  2. Glycine and GABAA receptors mediate tonic and phasic inhibitory processes that contribute to prepulse inhibition in the goldfish startle network

    Directory of Open Access Journals (Sweden)

    Paul C.P. Curtin

    2015-03-01

    Full Text Available Prepulse inhibition (PPI is understood as an inhibitory process that attenuates sensory flow during early stages (20-1000ms of information processing. Here, we applied in vivo electrophysiology and pharmacology to determine if prepulse inhibition (PPI is mediated by glycine receptors (GlyRs and/or GABAA receptors (GABAARs in the goldfish auditory startle circuit. Specifically, we used selective antagonists to dissect the contributions of target receptors on sound-evoked postsynaptic potentials (PSPs recorded in the neurons that initiate startle, the Mauthner-cells (M-cell. We found that strychnine, a GlyR antagonist, disrupted a fast-activated (5 ms and rapidly (< 50ms decaying (feed-forward inhibitory process that disrupts PPI at 20 ms prepulse/pulse inter-stimulus intervals (ISI. Additionally we observed increases of the evoked postsynaptic potential (PSP peak amplitude (+87.43 ± 21.53%; N=9 and duration (+204 ± 48.91%, N=9. In contrast, treatment with bicuculline, a GABAAR antagonist, caused a general reduction in PPI across all tested ISIs (20-500 ms, essentially eliminating PPI at ISIs from 20-100 ms. Bicuculline also increased PSP peak amplitude (+133.8 ± 10.3%, N=5 and PSP duration (+284.95 ± 65.64%, N=5. Treatment with either antagonist also tonically increased post-synaptic excitability in the M-cells, reflected by an increase in the magnitude of antidromically-evoked action potentials (APs by 15.07 ± 3.21%, N=7 and 16.23 ± 7.08%, N=5 for strychnine and bicuculline, respectively. These results suggest that GABAARs and GlyRs are functionally segregated to short- and longer-lasting sound-evoked (phasic inhibitory processes that contribute to PPI, with the mediation of tonic inhibition by both receptor systems being critical for gain control within the M-cell startle circuit.

  3. Two new lignans from Saururus chinensis and their DGAT inhibitory activity.

    Science.gov (United States)

    Li, Na; Tuo, Zhen-Dong; Qi, Shi-Zhou; Xing, Shan-Shan; Lee, Hyun-Sun; Chen, Jian-Guang; Cui, Long

    2015-03-01

    Two new lignans were isolated from Saururus chinensis, along with eight known compounds. Their structures were elucidated on the basis of spectroscopic and physico-chemical analyses. All the isolates were evaluated for in vitro inhibitory activity against DGAT1 and DGAT2. Among them, compounds 2, 3, 5 and 7 were found to exhibit selective inhibitory activity on DGAT1 with IC50 values ranging from 44.3±1.5 to 87.5±1.3μM. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Early adversity, RSA, and inhibitory control: evidence of children's neurobiological sensitivity to social context.

    Science.gov (United States)

    Skowron, Elizabeth A; Cipriano-Essel, Elizabeth; Gatzke-Kopp, Lisa M; Teti, Douglas M; Ammerman, Robert T

    2014-07-01

    This study examined parasympathetic physiology as a moderator of the effects of early adversity (i.e., child abuse and neglect) on children's inhibitory control. Children's respiratory sinus arrhythmia (RSA) was assessed during a resting baseline, two joint challenge tasks with mother, and an individual frustration task. RSA assessed during each of the joint parent-child challenge tasks moderated the effects of child maltreatment (CM) status on children's independently-assessed inhibitory control. No moderation effect was found for RSA assessed at baseline or in the child-alone challenge task. Among CM-exposed children, lower RSA levels during the joint task predicted the lowest inhibitory control, whereas higher joint task RSA was linked to higher inhibitory control scores that were indistinguishable from those of non-CM children. Results are discussed with regard to the importance of considering context specificity (i.e., individual and caregiver contexts) in how biomarkers inform our understanding of individual differences in vulnerability among at-risk children. © 2013 Wiley Periodicals, Inc.

  5. Fraction from human and rat liver which is inhibitory for proliferation of liver cells.

    Science.gov (United States)

    Chen, T S; Ottenweller, J; Luke, A; Santos, S; Keeting, P; Cuy, R; Lea, M A

    1989-01-01

    A comparative study was undertaken with human and rat liver of a fraction reported to have growth inhibitory activity when prepared from rat liver. Fractions which were soluble in 70% ethanol and insoluble in 87% ethanol were prepared from liver cytosols. Electrophoretic analysis under denaturing conditions indicated that there were several quantitative or qualitative differences in the fractions from the two species. Fractions from both human and rat liver were found to be inhibitory for the incorporation of 3H-thymidine into DNA of foetal chick hepatocytes. Under conditions in which the rat fraction inhibited precursor incorporation into DNA of rat liver epithelial cells there was not a significant inhibitory effect with the fraction from human liver. DNA synthesis in a rat hepatoma cell line was not significantly inhibited by preparations from either species. The data suggested that corresponding fractions from both rat and human liver could have inhibitory effects on precursor incorporation into DNA but the magnitude of the effects and target cell specificity may differ.

  6. α-Glucosidase and Protein Tyrosine Phosphatase 1B Inhibitory Activity of Plastoquinones from Marine Brown Alga Sargassum serratifolium

    Directory of Open Access Journals (Sweden)

    Md. Yousof Ali

    2017-12-01

    Full Text Available Sargassum serratifolium C. Agardh (Phaeophyceae, Fucales is a marine brown alga that belongs to the family Sargassaceae. It is widely distributed throughout coastal areas of Korea and Japan. S. serratifolium has been found to contain high concentrations of plastoquinones, which have strong anti-cancer, anti-inflammatory, antioxidant, and neuroprotective activity. This study aims to investigate the anti-diabetic activity of S. serratifolium and its major constituents through inhibition of protein tyrosine phosphatase 1B (PTP1B, α-glucosidase, and ONOO−-mediated albumin nitration. S. serratifolium ethanolic extract and fractions exhibited broad PTP1B and α-glucosidase inhibitory activity (IC50, 1.83~7.04 and 3.16~24.16 µg/mL for PTP1B and α-glucosidase, respectively. In an attempt to identify bioactive compounds, three plastoquinones (sargahydroquinoic acid, sargachromenol and sargaquinoic acid were isolated from the active n-hexane fraction of S. serratifolium. All three plastoquinones exhibited dose-dependent inhibitory activity against PTP1B in the IC50 range of 5.14–14.15 µM, while sargachromenol and sargaquinoic acid showed dose-dependent inhibitory activity against α-glucosidase (IC50 42.41 ± 3.09 and 96.17 ± 3.48 µM, respectively. In the kinetic study of PTP1B enzyme inhibition, sargahydroquinoic acid and sargaquinoic acid led to mixed-type inhibition, whereas sargachromenol displayed noncompetitive-type inhibition. Moreover, plastoquinones dose-dependently inhibited ONOO−-mediated albumin nitration. Docking simulations of these plastoquinones demonstrated negative binding energies and close proximity to residues in the binding pocket of PTP1B and α-glucosidase, indicating that these plastoquinones have high affinity and tight binding capacity towards the active site of the enzymes. These results demonstrate that S. serratifolium and its major plastoquinones may have the potential as functional food ingredients for the

  7. Production, optimisation and characterisation of angiotensin converting enzyme inhibitory peptides from sea cucumber (Stichopus japonicus) gonad.

    Science.gov (United States)

    Zhong, Chan; Sun, Le-Chang; Yan, Long-Jie; Lin, Yi-Chen; Liu, Guang-Ming; Cao, Min-Jie

    2018-01-24

    In this study, production of bioactive peptides with angiotensin converting enzyme (ACE) inhibitory activity from sea cucumber (Stichopus japonicus) gonad using commercial protamex was optimised by response surface methodology (RSM). As a result, the optimal condition to achieve the highest ACE inhibitory activity in sea cucumber gonad hydrolysate (SCGH) was hydrolysis for 1.95 h and E/S of 0.75%. For further characterisation, three individual peptides (EIYR, LF and NAPHMR) were purified and identified. The peptide NAPHMR showed the highest ACE inhibitory activity with IC 50 of 260.22 ± 3.71 μM. NAPHMR was stable against simulated gastrointestinal digestion and revealed no significant cytotoxicity toward Caco-2 cells. Molecular docking study suggested that Arg, His and Asn residues in NAPHMR interact with the S2 pocket or Zn 2+ binding motifs of ACE via hydrogen or π-bonds, potentially contributing to ACE inhibitory effect. Sea cucumber gonad is thus a potential resource to produce ACE inhibitory peptides for preparation of functional foods.

  8. Inhibitory effect of berberine on the invasion of human lung cancer cells via decreased productions of urokinase-plasminogen activator and matrix metalloproteinase-2

    International Nuclear Information System (INIS)

    Peng, P.-L.; Hsieh, Y.-S.; Wang, C.-J.; Hsu, J.-L.; Chou, F.-P.

    2006-01-01

    Berberine, a compound isolated from medicinal herbs, has been reported with many pharmacological effects related to anti-cancer and anti-inflammation capabilities. In this study, we observed that berberine exerted a dose- and time-dependent inhibitory effect on the motility and invasion ability of a highly metastatic A549 cells under non-cytotoxic concentrations. In cancer cell migration and invasion process, matrix-degrading proteinases are required. A549 cell treated with berberine at various concentrations showed reduced ECM proteinases including matrix metalloproteinase-2 (MMP2) and urokinase-plasminogen activator (u-PA) by gelatin and casein zymography analysis. The inhibitory effect is likely to be at the transcriptional level, since the reduction in the transcripts levels was corresponding to the proteins. Moreover, berberine also exerted its action via regulating tissue inhibitor of metalloproteinase-2 (TIMP-2) and urokinase-plasminogen activator inhibitor (PAI). The upstream mediators of the effect involved c-jun, c-fos and NF-κB, as evidenced by reduced phosphorylation of the proteins. These findings suggest that berberine possesses an anti-metastatic effect in non-small lung cancer cell and may, therefore, be helpful in clinical treatment

  9. Electronic Maxwell demon in the coherent strong-coupling regime

    Science.gov (United States)

    Schaller, Gernot; Cerrillo, Javier; Engelhardt, Georg; Strasberg, Philipp

    2018-05-01

    We consider an external feedback control loop implementing the action of a Maxwell demon. Applying control actions that are conditioned on measurement outcomes, the demon may transport electrons against a bias voltage and thereby effectively converts information into electric power. While the underlying model—a feedback-controlled quantum dot that is coupled to two electronic leads—is well explored in the limit of small tunnel couplings, we can address the strong-coupling regime with a fermionic reaction-coordinate mapping. This exact mapping transforms the setup into a serial triple quantum dot coupled to two leads. We find that a continuous projective measurement of the central dot occupation would lead to a complete suppression of electronic transport due to the quantum Zeno effect. In contrast, by using a microscopic detector model we can implement a weak measurement, which allows for closure of the control loop without transport blockade. Then, in the weak-coupling regime, the energy flows associated with the feedback loop are negligible, and dominantly the information gained in the measurement induces a bound for the generated electric power. In the strong coupling limit, the protocol may require more energy for operating the control loop than electric power produced, such that the whole device is no longer information dominated and can thus not be interpreted as a Maxwell demon.

  10. Tweets and Mobilisation: Collective Action Theory and Social Media

    Directory of Open Access Journals (Sweden)

    Cody McClain Brown

    2017-06-01

    Full Text Available This article examines the relationship between social protest and social media from the theoretical perspective of the Collective Action Research Program. While the literature shows strong empirical evidence for a positive relationship between social media use and incidents of social protest, the theoretical underpinnings of this relationship remain contested and often unspecified. In order to provide a stronger theoretical basis for this relationship this paper explores theories of collective action, focusing on how social media can assist in solving the dissident collective action problem. It argues that using collective action theory to understand social media and protest can better inform our understanding of how and why social media shares a positive relationship with incidents of social protest.

  11. Explaining radical group behavior: Developing emotion and efficacy routes to normative and nonnormative collective action.

    Science.gov (United States)

    Tausch, Nicole; Becker, Julia C; Spears, Russell; Christ, Oliver; Saab, Rim; Singh, Purnima; Siddiqui, Roomana N

    2011-07-01

    A recent model of collective action distinguishes 2 distinct pathways: an emotional pathway whereby anger in response to injustice motivates action and an efficacy pathway where the belief that issues can be solved collectively increases the likelihood that group members take action (van Zomeren, Spears, Fischer, & Leach, 2004). Research supporting this model has, however, focused entirely on relatively normative actions such as participating in demonstrations. We argue that the relations between emotions, efficacy, and action differ for more extreme, nonnormative actions and propose (a) that nonnormative actions are often driven by a sense of low efficacy and (b) that contempt, which, unlike anger, entails psychological distancing and a lack of reconciliatory intentions, predicts nonnormative action. These ideas were tested in 3 survey studies examining student protests against tuition fees in Germany (N = 332), Indian Muslims' action support in relation to ingroup disadvantage (N = 156), and British Muslims' responses to British foreign policy (N = 466). Results were generally supportive of predictions and indicated that (a) anger was strongly related to normative action but overall unrelated or less strongly related to nonnormative action, (b) contempt was either unrelated or negatively related to normative action but significantly positively predicted nonnormative action, and (c) efficacy was positively related to normative action and negatively related to nonnormative action. The implications of these findings for understanding and dealing with extreme intergroup phenomena such as terrorism are discussed. PsycINFO Database Record (c) 2011 APA, all rights reserved

  12. The Spillover Effects of Affirmative Action on Competitiveness and Unethical Behavior

    DEFF Research Database (Denmark)

    Banerjee, Ritwik; Gupta, Nabanita Datta; Villeval, Marie Claire

    We conduct an artefactual field experiment to examine various spillover effects of Affirmative Action policies in the context of castes in India. We test a) if individuals who compete in the presence of Affirmative Action policies remain competitive in the same proportion after the policy has been...... frequently a tournament payment scheme. However, we find no spillover effect on confidence and competitiveness once Affirmative Action is withdrawn: any lower caste’s gain in competitiveness due to the policy is then entirely wiped out. Furthermore, the strong existing bias of the dominant caste against...... the lower caste is not significantly aggravated by Affirmative Action....

  13. Improvement of ACE inhibitory activity of casein hydrolysate by Maillard reaction with xylose.

    Science.gov (United States)

    Hong, Xu; Meng, Jun; Lu, Rong-Rong

    2015-01-01

    The Maillard reaction is widely used to improve the functional properties or biological activities of food. The purpose of this study was to investigate the effect of the Maillard reaction on angiotensin I converting enzyme (ACE) inhibitory activity in a casein hydrolysate-xylose system. Two-step hydrolysis was used to prepare casein ACE inhibitory peptides. Maillard reaction products (MRPs) were prepared by heating hydrolyzed casein with xylose at pH 8.0, 110 °C for up to 16 h. The results showed that the content of free amino group decreased (P Maillard reaction (P reaction in the MRPs. The study shows that the Maillard reaction under appropriate conditions can improve the ACE inhibitory activity of casein hydrolysate effectively. © 2014 Society of Chemical Industry.

  14. The quantum Zeno and anti-Zeno effects with strong system-environment coupling.

    Science.gov (United States)

    Chaudhry, Adam Zaman

    2017-05-11

    To date, studies of the quantum Zeno and anti-Zeno effects focus on quantum systems that are weakly interacting with their environment. In this paper, we investigate what happens to a quantum system under the action of repeated measurements if the quantum system is strongly interacting with its environment. We consider as the quantum system a single two-level system coupled strongly to a collection of harmonic oscillators. A so-called polaron transformation is then used to make the problem in the strong system-environment coupling regime tractable. We find that the strong coupling case exhibits quantitative and qualitative differences as compared with the weak coupling case. In particular, the effective decay rate does not depend linearly on the spectral density of the environment. This then means that, in the strong coupling regime that we investigate, increasing the system-environment coupling strength can actually decrease the effective decay rate. We also consider a collection of two-level atoms coupled strongly with a common environment. In this case, we find that there are further differences between the weak and strong coupling cases since the two-level atoms can now indirectly interact with one another due to the common environment.

  15. Immune inhibitory receptors in viral infection and cancer

    NARCIS (Netherlands)

    Karnam, G.

    2014-01-01

    We are protected from external and internal dangers by our immune system. Immune responses need to be balanced to prevent uncontrolled inflammation and/or autoimmunity. Cell growth inhibition, apoptosis, and down regulation of receptor signals are all part of the inhibitory tools used by the immune

  16. Sleep Supports Inhibitory Operant Conditioning Memory in "Aplysia"

    Science.gov (United States)

    Vorster, Albrecht P. A.; Born, Jan

    2017-01-01

    Sleep supports memory consolidation as shown in mammals and invertebrates such as bees and "Drosophila." Here, we show that sleep's memory function is preserved in "Aplysia californica" with an even simpler nervous system. Animals performed on an inhibitory conditioning task ("learning that a food is inedible") three…

  17. Inhibitory effect of chitosan oligosaccharide on human hepatoma ...

    African Journals Online (AJOL)

    Background: Chitosan oligosaccharide, the degradation products of chitin, was reported to have a wide range of physiological functions and biological activities. In this study, we explored the inhibitory effect of Chitosan oligosaccharide on human hepatoma cells. Materials and Methods: MTT assay was applied to detect cell ...

  18. Studies on the biosynthesis of macrophage migration inhibitory factor in delayed hypersensitivity, 1. Effects of inhibitors of nucleic acid and protein synthesis on the production of macrophage migration inhibitory factor

    Energy Technology Data Exchange (ETDEWEB)

    Mizoguchi, Y; Yamamoto, S; Morisawa, S [Osaka City Univ. (Japan). Faculty of Medicine

    1973-03-01

    Specific antigenic stimulation of sensitized lymphocytes leads to the production of macrophage migration inhibitory factor (MIF). Production of MIF is inhibited by mitomycin C, actinomycin D, and puromycin. These inhibition effects are studied by using thymidine-/sup 3/H. The first two of these antibiotics only inhibit MIF production when added to the culture medium at a very early stage of antigenic stimulation. In contrast, puromycin exerts its inhibitory effect several hours after the antigenic stimulation, but not at an earlier stage. MIF behaves like a protein, so it seems likely that synthesis of RNA is necessary for MIF formation and MIF synthesis may start as early as a few hours after specific antigenic activation of the sensitized lymphocytes. The inhibitory effects of the antibiotics are discussed in relation to the kinetics of MIF production.

  19. Investigating conceptions of intentional action by analyzing participant generated scenarios

    Science.gov (United States)

    Skulmowski, Alexander; Bunge, Andreas; Cohen, Bret R.; Kreilkamp, Barbara A. K.; Troxler, Nicole

    2015-01-01

    We describe and report on results of employing a new method for analyzing lay conceptions of intentional and unintentional action. Instead of asking people for their conceptual intuitions with regard to construed scenarios, we asked our participants to come up with their own scenarios and to explain why these are examples of intentional or unintentional actions. By way of content analysis, we extracted contexts and components that people associated with these action types. Our participants associated unintentional actions predominantly with bad outcomes for all persons involved and linked intentional actions more strongly to positive outcomes, especially concerning the agent. People’s conceptions of intentional action seem to involve more aspects than commonly assumed in philosophical models of intentional action that solely stress the importance of intentions, desires, and beliefs. The additional aspects include decisions and thoughts about the action. In addition, we found that the criteria that participants generated for unintentional actions are not a mere inversion of those used in explanations for intentional actions. Associations between involuntariness and unintentional action seem to be stronger than associations between aspects of voluntariness and intentional action. PMID:26594182

  20. Antibacterial and glucosyltransferase enzyme inhibitory activity of helmyntostachyszelanica

    Science.gov (United States)

    Kuspradini, H.; Putri, AS; Mitsunaga, T.

    2018-04-01

    Helminthostachyszeylanica is a terrestrial, herbaceous, fern-like plant of southeastern Asia and Australia, commonly known as tunjuk-langit. This kind of plant have a medicinal properties such as treatment of malaria, dysentery and can be eaten with betel in the treatment of whooping cough. To evaluate the scientific basis for the use of the plant, the antimicrobial activities of extracts of the stem and leaves were evaluated. The bacteria used in this study is Streptococcus sobrinus, a species of gram-positive, that may be associated with human dental caries. The dried powdered plant parts were extracted using methanol and 50% aqueous extract and screened for their antibacterial effects of Streptococcus sobrinus using the 96 well-plate microdilution broth method. The inhibitory activities of its related enzyme were also determined. The plant extracts showed variable antibacterial and Glucosyltransferase enzyme inhibitory activity while some extracts could not cause any inhibition. It was shown that 50% ethanolics of Helminthostachyzeylanica stem have a potency as anti dental caries agents.

  1. Discrimination and Nitric Oxide Inhibitory Activity Correlation of Ajwa Dates from Different Grades and Origin

    Directory of Open Access Journals (Sweden)

    Nur Ashikin Abdul-Hamid

    2016-10-01

    Full Text Available This study was aimed at examining the variations in the metabolite constituents of the different Ajwa grades and farm origins. It is also targeted at establishing the correlations between the metabolite contents and the grades and further to the nitric oxide (NO inhibitory activity. Identification of the metabolites was generated using 1H-NMR spectroscopy metabolomics analyses utilizing multivariate methods. The NO inhibitory activity was determined using a Griess assay. Multivariate data analysis, for both supervised and unsupervised approaches, showed clusters among different grades of Ajwa dates obtained from different farms. The compounds that contribute towards the observed separation between Ajwa samples were suggested to be phenolic compounds, ascorbic acid and phenylalanine. Ajwa dates were shown to have different metabolite compositions and exhibited a wide range of NO inhibitory activity. It is also revealed that Ajwa Grade 1 from the al-Aliah farm exhibited more than 90% NO inhibitory activity compared to the other grades and origins. Phenolic compounds were among the compounds that played a role towards the greater capacity of NO inhibitory activity shown by Ajwa Grade 1 from the al-Aliah farm.

  2. The inhibitory effect of metals and other ions on acid phosphatase activity from Vigna aconitifolia seeds.

    Science.gov (United States)

    Srivastava, Pramod Kumar; Anand, Asha

    2015-01-01

    Sensitivity of acid phosphatase from Vigna aconitifolia seeds to metal ions, fluoride, and phosphate was examined. All the effectors had different degree of inhibitory effect on the enzyme. Among metal ions, molybdate and ferric ion were observed to be most potent inhibitors and both exhibited mixed type of inhibition. Acid phosphatase activity was inhibited by Cu2+ in a noncompetitive manner. Zn and Mn showed mild inhibition on the enzyme activity. Inhibition kinetics analysis explored molybdate as a potent inhibitor for acid phosphatase in comparison with other effectors used in this study. Fluoride was the next most strong inhibitor for the enzyme activity, and caused a mixed type of inhibition. Phosphate inhibited the enzyme competitively, which demonstrates that inhibition due to phosphate is one of the regulatory factors for enzyme activity.

  3. Growth inhibitory action of ebselen on fluconazole-resistant Candida albicans: role of the plasma membrane H+-ATPase.

    Science.gov (United States)

    Billack, Blase; Santoro, Michelle; Lau-Cam, Cesar

    2009-06-01

    PMA1 is a yeast gene that codes for the plasma membrane H(+)-ATPase, a protein commonly referred to as Pma1p. Ebselen (2-phenyl-1,2-benzisoselenazol-3(2H)-one) is a synthetic selenium-containing compound that has recently been shown to display antimicrobial activity owing to its ability to inhibit Pma1p. Ebselen is able to block the activity of Pma1p not only in opportunistic pathogens such as Cryptococcus neoformans and Candida albicans but also in nonpathogenic yeasts such as Saccharomyces cerevisiae. A series of in vitro studies aimed at evaluating the antifungal activity of ebselen were performed. At low concentrations (ebselen was fungistatic against three strains of S. cerevisiae (IC(50) approximately 3 microM) and one fluconazole-resistant strain of C. albicans (IC(50) approximately 6 microM), and at a high concentration (30 microM) it was fungicidal against C. albicans. Moreover, ebselen was found to inhibit medium acidification by the fluconazole-resistant strain of C. albicans in a concentration-dependent manner. In comparison to currently used antifungal agents represented by azole (itraconazole, ketoconazole, fluconazole) and polyene (amphotericin B) compounds, ebselen was at least 10-fold more potent than fluconazole but less active than the other compounds tested. The present results suggest that the growth inhibitory activity of ebselen toward fluconazole-resistant yeast cells is due, at least in part, to inhibition of Pma1p. Ebselen may also serve as a useful agent in the treatment of infections caused by fluconazole-resistant fungi.

  4. Inhibitory effect of interferon-γ on experimental tooth movement in mice.

    Science.gov (United States)

    Kohara, Haruka; Kitaura, Hideki; Yoshimatsu, Masako; Fujimura, Yuji; Morita, Yukiko; Eguchi, Toshiko; Yoshida, Noriaki

    2012-09-01

    The aim of this study was to investigate the effects of interferon (IFN)-γ on experimental tooth movement in mice using a murine experimental tooth movement model. An Ni-Ti closed-coil spring was inserted between the upper-anterior alveolar bones and the upper-left first molars in mice. We evaluated the relationship between local Ifn-γ mRNA levels and orthodontic tooth movement. In other experiments, IFN-γ was injected adjacent to each first molar every other day during tooth movement. After 12 days, the amount of tooth movement was measured. Tartrate-resistant acid phosphatase (TRAP)-positive cells at the pressure side of each experimental tooth were counted as osteoclasts. Local Ifn-γ mRNA expression increased with orthodontic tooth movement. The number of TRAP-positive cells increased on the pressure side of the first molar. In contrast, the degree of tooth movement and the number of TRAP-positive cells on the pressure side in IFN-γ-injected mice were less than those of control mice. IFN-γ was induced in experimental tooth movement, and could inhibit mechanical force-loaded osteoclastogenesis and tooth movement. These results suggest that IFN-γ might be useful in controlling orthodontic tooth movement because of its inhibitory action on excessive osteoclastogenesis during this movement.

  5. Isolation of prolyl endopeptidase inhibitory peptides from a sodium caseinate hydrolysate.

    Science.gov (United States)

    Hsieh, Cheng-Hong; Wang, Tzu-Yuan; Hung, Chuan-Chuan; Hsieh, You-Liang; Hsu, Kuo-Chiang

    2016-01-01

    Prolyl endopeptidase (PEP) has been associated with neurodegenerative disorders, and the PEP inhibitors can restore the memory loss caused by amnesic compounds. In this study, we investigated the PEP inhibitory activity of the enzymatic hydrolysates from various food protein sources, and isolated and identified the PEP inhibitory peptides. The hydrolysate obtained from sodium caseinate using bromelain (SC/BML) displayed the highest inhibitory activity of 86.8% at 5 mg mL(-1) in the present study, and its IC50 value against PEP was 0.77 mg mL(-1). The F-5 fraction by RP-HPLC (reversed-phase high performance liquid chromatography) from SC/BML showed the highest PEP inhibition rate of 88.4%, and 9 peptide sequences were identified. The synthetic peptides (1245.63-1787.94 Da) showed dose-dependent inhibition effects on PEP as competitive inhibitors with IC50 values between 29.8 and 650.5 μM. The results suggest that the peptides derived from sodium caseinate have the potential to be PEP inhibitors.

  6. Antioxidant and α-glucosidase inhibitory ingredients identified from Jerusalem artichoke flowers.

    Science.gov (United States)

    Wang, Yan-Ming; Zhao, Jian-Qiang; Yang, Jun-Li; Idong, Pema Tsering; Mei, Li-Juan; Tao, Yan-Duo; Shi, Yan-Ping

    2017-11-09

    Jerusalem artichoke (JA, Helianthus tuberosus L.) has been researched extensively due to its wide range of uses, but there are limited studies on its flowers. In this study, we report the first detailed phytochemical study on JA flowers, which yielded 21 compounds. Compound 4 was identified as a major water-soluble yellow pigment of JA flowers. In addition, the methanol extract of JA flowers and the isolates were evaluated for their antioxidant and α-glucosidase inhibitory activities. Among the tested compounds, compound 13 showed the strongest ABTS + free radical scavenging activity with SC 50 value of 2.30 ± 0.13 μg/mL, and compound 6 showed most potent α-glucosidase inhibitory activity with inhibition rate of 60.0% ± 10.3% at a concentration of 250 μg/mL. Results showed that methanol extract of JA flowers exhibited antioxidant and α-glucosidase inhibitory activities which could be attributed to its phenolic ingredients including chlorogenic acid derivatives, flavonoids and phenols.

  7. The influence of action-effect anticipation on bistable perception: Differences between onset rivalry and ambiguous motion

    NARCIS (Netherlands)

    Dogge, M.; Gayet, S.; Custers, R.; Aarts, H.A.G.

    2018-01-01

    Perception is strongly shaped by the actions we perform. According to the theory of event coding, and forward models of motor control, goal-directed action preparation activates representations of desired effects. These expectations about the precise stimulus identity of one's action-outcomes (i.e.

  8. Inhibitory Control in Speech Comprehension among Dai–Han Bilingual Children

    Directory of Open Access Journals (Sweden)

    Yun Tao

    2017-08-01

    Full Text Available We aimed to investigate differences in inhibitory control ability between proficient and non-proficient Dai–Han bilinguals. Two experiments used a combined stimulus–stimulus and stimulus–response compatibility paradigm for this purpose. Participants were Dai–Han bilingual primary-school students selected from a Dai-speaking town in Yunnan province, China. In Dai language interference condition, participants were asked to complete a picture category task. Results showed that the effect of attentional control for non-proficient bilinguals (NPBs was significantly greater than that for proficient bilinguals (PBs, while the effect of response inhibition was not. This implied that a difference in inhibitory control between PBs and NPBs appeared at the attention control stage when interference by the Dai lexicon emerged. In Han language interference condition, however, participants were also asked to complete the same task. Results showed that the effect of response inhibition for NPBs was significantly greater than that for PBs, but the effect of attentional control was not. This demonstrated that a difference in inhibitory control emerged at the response inhibition stage when interference by the Han lexicon emerged. This pattern of results is opposite to previous researches, which indicated that the difference between PBs and NPBs occurred at the response inhibition stage under first language condition, whereas at the attentional control stage under second language (L2 condition. Based on these, this study suggests that Dai–Han bilinguals showed a remarkable L2 advantage. In addition, results showed that response times (RTs of PBs were faster than RTs of NPBs while confounding variables (e.g., intelligence, etc. were under control. This indicates that the inhibitory control ability of the PBs is superior to that of NPBs in this study.

  9. Competition as rational action: why young children cannot appreciate competitive games.

    Science.gov (United States)

    Priewasser, Beate; Roessler, Johannes; Perner, Josef

    2013-10-01

    Understanding rational actions requires perspective taking both with respect to means and with respect to objectives. This study addresses the question of whether the two kinds of perspective taking develop simultaneously or in sequence. It is argued that evidence from competitive behavior is best suited for settling this issue. A total of 71 kindergarten children between 3 and 5 years of age participated in a competitive game of dice and were tested on two traditional false belief stories as well as on several control tasks (verbal intelligence, inhibitory control, and working memory). The frequency of competitive poaching moves in the game correlated with correct predictions of mistaken actions in the false belief task. Hierarchical linear regression after controlling for age and control variables showed that false belief understanding significantly predicted the amount of poaching moves. The results speak for an interrelated development of the capacity for "instrumental" and "telic" perspective taking. They are discussed in the light of teleology as opposed to theory use and simulation. Copyright © 2012 Elsevier Inc. All rights reserved.

  10. Chemical-genetic profile analysis of five inhibitory compounds in yeast.

    Science.gov (United States)

    Alamgir, Md; Erukova, Veronika; Jessulat, Matthew; Azizi, Ali; Golshani, Ashkan

    2010-08-06

    Chemical-genetic profiling of inhibitory compounds can lead to identification of their modes of action. These profiles can help elucidate the complex interactions between small bioactive compounds and the cell machinery, and explain putative gene function(s). Colony size reduction was used to investigate the chemical-genetic profile of cycloheximide, 3-amino-1,2,4-triazole, paromomycin, streptomycin and neomycin in the yeast Saccharomyces cerevisiae. These compounds target the process of protein biosynthesis. More than 70,000 strains were analyzed from the array of gene deletion mutant yeast strains. As expected, the overall profiles of the tested compounds were similar, with deletions for genes involved in protein biosynthesis being the major category followed by metabolism. This implies that novel genes involved in protein biosynthesis could be identified from these profiles. Further investigations were carried out to assess the activity of three profiled genes in the process of protein biosynthesis using relative fitness of double mutants and other genetic assays. Chemical-genetic profiles provide insight into the molecular mechanism(s) of the examined compounds by elucidating their potential primary and secondary cellular target sites. Our follow-up investigations into the activity of three profiled genes in the process of protein biosynthesis provided further evidence concerning the usefulness of chemical-genetic analyses for annotating gene functions. We termed these genes TAE2, TAE3 and TAE4 for translation associated elements 2-4.

  11. Effect of partially purified angiotensin converting enzyme inhibitory ...

    African Journals Online (AJOL)

    This study evaluated the effect of partially-purified angiotensin converting enzyme (ACE) inhibitory proteins obtained from the leaves of Moringa oleifera on blood glucose, serum ACE activity and lipid profile of alloxaninduced diabetic rats. Twenty-five apparently healthy male albino rats were divided into five groups of five ...

  12. Altruistic sharing behavior in children: Role of theory of mind and inhibitory control.

    Science.gov (United States)

    Liu, Buyun; Huang, Zhelan; Xu, Guifeng; Jin, Yu; Chen, Yajun; Li, Xiuhong; Wang, Qingxiong; Song, Shanshan; Jing, Jin

    2016-01-01

    This study aimed to assess altruistic sharing behavior in children aged 3 to 5, 6 to 8, and 9 to 11 years and to explore the involvement of potential cognitive mechanisms, namely theory of mind (ToM) and inhibitory control. A total of 158 children completed a dictator game with stickers as incentives. ToM was evaluated using a false belief task in preschoolers and the Strange Story Test in school-age children. Inhibitory control was assessed in preschoolers with the Day-Night task and in older children with the Stroop Color-Word Test. The result was that 48.10% of children aged 3 to 5 years decided to share, and the percentage rose significantly with increasing age. The difference in altruism level in children who decided to share among the three age groups was nonsignificant. These results suggest that mechanisms underlying the decision to share or not and altruistic behavior may be different. No significant linear relations were found between cognitive processes (i.e., ToM and inhibitory control) and sharing behavior. Surprisingly, 9- to 11-year-olds who shared 3 of 10 stickers performed worse in inhibitory control than did those who shared any other number of stickers. In conclusion, the proportion of children who decided to share, but not the level of altruism, increased with age. ToM was not involved in altruistic sharing, whereas inhibitory control may play a role when deciding how much to share. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Accelerating early anti-tuberculosis drug discovery by creating mycobacterial indicator strains that predict mode of action

    KAUST Repository

    Boot, Maikel

    2018-04-13

    Due to the rise of drug resistant forms of tuberculosis there is an urgent need for novel antibiotics to effectively combat these cases and shorten treatment regimens. Recently, drug screens using whole cell analyses have been shown to be successful. However, current high-throughput screens focus mostly on stricto sensu life-death screening that give little qualitative information. In doing so, promising compound scaffolds or non-optimized compounds that fail to reach inhibitory concentrations are missed. To accelerate early TB drug discovery, we performed RNA sequencing on Mycobacterium tuberculosis and Mycobacterium marinum to map the stress responses that follow upon exposure to sub-inhibitory concentrations of antibiotics with known targets: ciprofloxacin, ethambutol, isoniazid, streptomycin and rifampicin. The resulting dataset comprises the first overview of transcriptional stress responses of mycobacteria to different antibiotics. We show that antibiotics can be distinguished based on their specific transcriptional stress fingerprint. Notably, this fingerprint was more distinctive in M. marinum. We decided to use this to our advantage and continue with this model organism. A selection of diverse antibiotic stress genes was used to construct stress reporters. In total, three functional reporters were constructed to respond to DNA damage, cell wall damage and ribosomal inhibition. Subsequently, these reporter strains were used to screen a small anti-TB compound library to predict the mode of action. In doing so, we could identify the putative mode of action for three novel compounds, which confirms our approach.

  14. Genetic controls balancing excitatory and inhibitory synaptogenesis in neurodevelopmental disorder models

    Directory of Open Access Journals (Sweden)

    Cheryl L Gatto

    2010-06-01

    Full Text Available Proper brain function requires stringent balance of excitatory and inhibitory synapse formation during neural circuit assembly. Mutation of genes that normally sculpt and maintain this balance results in severe dysfunction, causing neurodevelopmental disorders including autism, epilepsy and Rett syndrome. Such mutations may result in defective architectural structuring of synaptic connections, molecular assembly of synapses and/or functional synaptogenesis. The affected genes often encode synaptic components directly, but also include regulators that secondarily mediate the synthesis or assembly of synaptic proteins. The prime example is Fragile X syndrome (FXS, the leading heritable cause of both intellectual disability and autism spectrum disorders. FXS results from loss of mRNA-binding FMRP, which regulates synaptic transcript trafficking, stability and translation in activity-dependent synaptogenesis and plasticity mechanisms. Genetic models of FXS exhibit striking excitatory and inhibitory synapse imbalance, associated with impaired cognitive and social interaction behaviors. Downstream of translation control, a number of specific synaptic proteins regulate excitatory versus inhibitory synaptogenesis, independently or combinatorially, and loss of these proteins is also linked to disrupted neurodevelopment. The current effort is to define the cascade of events linking transcription, translation and the role of specific synaptic proteins in the maintenance of excitatory versus inhibitory synapses during neural circuit formation. This focus includes mechanisms that fine-tune excitation and inhibition during the refinement of functional synaptic circuits, and later modulate this balance throughout life. The use of powerful new genetic models has begun to shed light on the mechanistic bases of excitation/inhibition imbalance for a range of neurodevelopmental disease states.

  15. Investigating Inhibitory Control in Children with Epilepsy: An fMRI Study

    Science.gov (United States)

    Triplett, Regina L.; Velanova, Katerina; Luna, Beatriz; Padmanabhan, Aarthi; Gaillard, William D.; Asato, Miya R.

    2014-01-01

    SUMMARY Objective Deficits in executive function are increasingly noted in children with epilepsy and have been associated with poor academic and psychosocial outcomes. Impaired inhibitory control contributes to executive dysfunction in children with epilepsy; however, its neuroanatomic basis has not yet been investigated. We used functional Magnetic Resonance Imaging (fMRI) to probe the integrity of activation in brain regions underlying inhibitory control in children with epilepsy. Methods This cross-sectional study consisted of 34 children aged 8 to 17 years: 17 with well-controlled epilepsy and 17 age-and sex-matched controls. Participants performed the antisaccade (AS) task, representative of inhibitory control, during fMRI scanning. We compared AS performance during neutral and reward task conditions and evaluated task-related blood-oxygen level dependent (BOLD) activation. Results Children with epilepsy demonstrated impaired AS performance compared to controls during both neutral (non-reward) and reward trials, but exhibited significant task improvement during reward trials. Post-hoc analysis revealed that younger patients made more errors than older patients and all controls. fMRI results showed preserved activation in task-relevant regions in patients and controls, with the exception of increased activation in the left posterior cingulate gyrus in patients specifically with generalized epilepsy across neutral and reward trials. Significance Despite impaired inhibitory control, children with epilepsy accessed typical neural pathways as did their peers without epilepsy. Children with epilepsy showed improved behavioral performance in response to the reward condition, suggesting potential benefits of the use of incentives in cognitive remediation. PMID:25223606

  16. Quantitative evaluation of inhibitory effect of various substances on anaerobic ammonia oxidation (anammox).

    Science.gov (United States)

    Nakamura, Tomotaka; Harigaya, Yuhki; Kimura, Yuya; Kuroiwa, Megumi; Kurata, Yuhri; Isaka, Kazuichi; Suwa, Yuichi

    2017-09-01

    The inhibitory effect of 20 substances of various chemical species on the anaerobic ammonia oxidation (anammox) activity of an enrichment culture, predominated by Candidatus Brocadia, was determined systematically by using a 15 N tracer technique. The initial anammox rate was determined during first 25 min with a small-scale anaerobic batch incubation supplemented with possible inhibitors. Although Cu 2+ and Mn 2+ did not inhibit anammox, the remaining 18 substances [Ni 2+ , Zn 2+ , Co 2+ , [Formula: see text] , Fe 2+ , 4 amines, ethylenediaminetetraacetic acid (EDTA), ethylenediamine-N,N'-bis (2-hydroxyphenylacetic acid) (EDDHA), citric acid, nitrilotriacetic acid (NTA), N,N-dimethylacetamide (DMA), 1,4-dioxane, dimethyl sulfoxide (DMSO), N,N-dimethylformamide (DMF) and tetrahydrofuran (THF)] were inhibitory. Inhibitory effect of NTA, EDDHA, THF, DMF, DMA and amines on anammox was first determined in this study. Inhibitory effects of metals were re-evaluated because chelators, which may interfere inhibitory effect, have been used to dissolve metal salts into assay solution. The relative anammox activities as a function of concentration of each substance were described successfully (R 2  > 0.91) either with a linear inhibition model or with a Michaelis-Menten-based inhibition model. IC 50 values were estimated based on either model, and were compared. The IC 50 values of the 4 chelators (0.06-2.7 mM) and 5 metal ions (0.02-1.09 mM) were significantly lower than those of the 4 amines (10.6-29.1 mM) and 5 organic solvents (3.5-82 mM). Although it did not show any inhibition within 25 min, 0.1 mM Cu 2+ completely inhibited anammox activity in 240 min, suggesting that the inhibitory effect caused by Cu 2+ is time-dependent. Copyright © 2017 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  17. Strategies for combating bacterial biofilms: A focus on anti-biofilm agents and their mechanisms of action

    Science.gov (United States)

    Roy, Ranita; Tiwari, Monalisa; Donelli, Gianfranco; Tiwari, Vishvanath

    2018-01-01

    ABSTRACT Biofilm refers to the complex, sessile communities of microbes found either attached to a surface or buried firmly in an extracellular matrix as aggregates. The biofilm matrix surrounding bacteria makes them tolerant to harsh conditions and resistant to antibacterial treatments. Moreover, the biofilms are responsible for causing a broad range of chronic diseases and due to the emergence of antibiotic resistance in bacteria it has really become difficult to treat them with efficacy. Furthermore, the antibiotics available till date are ineffective for treating these biofilm related infections due to their higher values of minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC), which may result in in-vivo toxicity. Hence, it is critically important to design or screen anti-biofilm molecules that can effectively minimize and eradicate biofilm related infections. In the present article, we have highlighted the mechanism of biofilm formation with reference to different models and various methods used for biofilm detection. A major focus has been put on various anti-biofilm molecules discovered or tested till date which may include herbal active compounds, chelating agents, peptide antibiotics, lantibiotics and synthetic chemical compounds along with their structures, mechanism of action and their respective MICs, MBCs, minimum biofilm inhibitory concentrations (MBICs) as well as the half maximal inhibitory concentration (IC50) values available in the literature so far. Different mode of action of anti biofilm molecules addressed here are inhibition via interference in the quorum sensing pathways, adhesion mechanism, disruption of extracellular DNA, protein, lipopolysaccharides, exopolysaccharides and secondary messengers involved in various signaling pathways. From this study, we conclude that the molecules considered here might be used to treat biofilm-associated infections after significant structural modifications, thereby

  18. Computer Simulations Support a Morphological Contribution to BDNF Enhancement of Action Potential Generation

    Directory of Open Access Journals (Sweden)

    Domenico F Galati

    2016-09-01

    Full Text Available Abstract Brain-derived neurotrophic factor (BDNF regulates both action potential (AP generation and neuron morphology. However, whether BDNF-induced changes in neuron morphology directly impact AP generation is unclear. We quantified BDNF’s effect on cultured cortical neuron morphological parameters and found that BDNF stimulates dendrite growth and addition of dendrites while increasing both excitatory and inhibitory presynaptic inputs in a spatially restricted manner. To gain insight into how these combined changes in neuron structure and synaptic input impact AP generation, we used the morphological parameters we gathered to generate computational models. Simulations suggest that BDNF-induced neuron morphologies generate more APs under a wide variety of conditions. Synapse and dendrite addition have the greatest impact on AP generation. However, subtle alterations in excitatory/inhibitory synapse ratio and strength have a significant impact on AP generation when synaptic activity is low. Consistent with these simulations, BDNF rapidly enhances spontaneous activity in cortical cultures. We propose that BDNF promotes neuron morphologies that are intrinsically more efficient at translating barrages of synaptic activity into APs, which is a previously unexplored aspect of BDNF’s function.

  19. Role of inhibitory feedback for information processing in thalamocortical circuits

    International Nuclear Information System (INIS)

    Mayer, Joerg; Schuster, Heinz Georg; Claussen, Jens Christian

    2006-01-01

    The information transfer in the thalamus is blocked dynamically during sleep, in conjunction with the occurrence of spindle waves. In order to describe the dynamic mechanisms which control the sensory transfer of information, it is necessary to have a qualitative model for the response properties of thalamic neurons. As the theoretical understanding of the mechanism remains incomplete, we analyze two modeling approaches for a recent experiment by Le Masson et al. [Nature (London) 417, 854 (2002)] on the thalamocortical loop. We use a conductance based model in order to motivate an extension of the Hindmarsh-Rose model, which mimics experimental observations of Le Masson et al. Typically, thalamic neurons posses two different firing modes, depending on their membrane potential. At depolarized potentials, the cells fire in a single spike mode and relay synaptic inputs in a one-to-one manner to the cortex. If the cell gets hyperpolarized, T-type calcium currents generate burst-mode firing which leads to a decrease in the spike transfer. In thalamocortical circuits, the cell membrane gets hyperpolarized by recurrent inhibitory feedback loops. In the case of reciprocally coupled excitatory and inhibitory neurons, inhibitory feedback leads to metastable self-sustained oscillations, which mask the incoming input, and thereby reduce the information transfer significantly

  20. Studies on the biosynthesis of macrophage migration inhibitory factor in delayed hypersensitivity, 1

    International Nuclear Information System (INIS)

    Mizoguchi, Yasuhiro; Yamamoto, Sukeo; Morisawa, Seiji

    1973-01-01

    Specific antigenic stimulation of sensitized lymphocytes leads to the production of macrophage migration inhibitory factor (MIF). Production of MIF is inhibited by mitomycin C, actinomycin D, and puromycin. These inhibition effects are studied by using thymidine- 3 H. The first two of these antibiotics only inhibit MIF production when added to the culture medium at a very early stage of antigenic stimulation. In contrast, puromycin exerts its inhibitory effect several hours after the antigenic stimulation, but not at an earlier stage. MIF behaves like a protein, so it seems likely that synthesis of RNA is necessary for MIF formation and MIF synthesis may start as early as a few hours after specific antigenic activation of the sensitized lymphocytes. The inhibitory effects of the antibiotics are discussed in relation to the kinetics of MIF production. (author)

  1. [Working memory and executive control: inhibitory processes in updating and random generation tasks].

    Science.gov (United States)

    Macizo, Pedro; Bajo, Teresa; Soriano, Maria Felipa

    2006-02-01

    Working Memory (WM) span predicts subjects' performance in control executive tasks and, in addition, it has been related to the capacity to inhibit irrelevant information. In this paper we investigate the role of WM span in two executive tasks focusing our attention on inhibitory components of both tasks. High and low span participants recalled targets words rejecting irrelevant items at the same time (Experiment 1) and they generated random numbers (Experiment 2). Results showed a clear relation between WM span and performance in both tasks. In addition, analyses of intrusion errors (Experiment 1) and stereotyped responses (Experiment 2) indicated that high span individuals were able to efficiently use the inhibitory component implied in both tasks. The pattern of data provides support to the relation between WM span and control executive tasks through an inhibitory mechanism.

  2. Identification of Angiotensin I-Converting Enzyme Inhibitory Peptides Derived from Enzymatic Hydrolysates of Razor Clam Sinonovacula constricta

    Directory of Open Access Journals (Sweden)

    Yun Li

    2016-06-01

    Full Text Available Angiotensin I-converting enzyme (ACE inhibitory activity of razor clam hydrolysates produced using five proteases, namely, pepsin, trypsin, alcalase, flavourzyme and proteases from Actinomucor elegans T3 was investigated. Flavourzyme hydrolysate showed the highest level of degree of hydrolysis (DH (45.87% followed by A. elegans T3 proteases hydrolysate (37.84% and alcalase (30.55%. The A. elegans T3 proteases was observed to be more effective in generating small peptides with ACE-inhibitory activity. The 3 kDa membrane permeate of A. elegans T3 proteases hydrolysate showed the highest ACE-inhibitory activity with an IC50 of 0.79 mg/mL. After chromatographic separation by Sephadex G-15 gel filtration and reverse phase-high performance liquid chromatography, the potent fraction was subjected to MALDI/TOF-TOF MS/MS for identification. A novel ACE-inhibitory peptide (VQY was identified exhibiting an IC50 of 9.8 μM. The inhibitory kinetics investigation by Lineweaver-Burk plots demonstrated that the peptide acts as a competitive ACE inhibitor. The razor clam hydrolysate obtained by A. elegans T3 proteases could serve as a source of functional peptides with ACE-inhibitory activity for physiological benefits.

  3. Analysis and Evaluation of the Inhibitory Mechanism of a Novel Angiotensin-I-Converting Enzyme Inhibitory Peptide Derived from Casein Hydrolysate.

    Science.gov (United States)

    Tu, Maolin; Liu, Hanxiong; Zhang, Ruyi; Chen, Hui; Mao, Fengjiao; Cheng, Shuzhen; Lu, Weihong; Du, Ming

    2018-04-25

    Casein hydrolysates exert various biological activities, and the responsible functional peptides are being identified from them continuously. In this study, the tryptic casein hydrolysate was fractionated by an ultrafiltration membrane (3 kDa), and the peptides were identified by capillary electrophoresis-quadrupole-time-of-flight-tandem mass spectrometry. Meanwhile, in silico methods were used to analyze the toxicity, solubility, stability, and affinity between the peptides and angiotensin-I-converting enzyme (ACE). Finally, a new angiotensin-I-converting enzyme inhibitory (ACEI) peptide, EKVNELSK, derived from α s1 -casein (fragment 35-42) was screened. The half maximal inhibitory concentration value of the peptide is 5.998 mM, which was determined by a high-performance liquid chromatography method. The Lineweaver-Burk plot indicated that this peptide is a mixed-type inhibitor against ACE. Moreover, Discovery Studio 2017 R2 software was adopted to perform molecular docking to propose the potential mechanisms underlying the ACEI activity of the peptide. These results indicated that EKVNELSK is a new ACEI peptide identified from casein hydrolysate.

  4. Simulated inhibitory effects of typical byproducts of biomass ...

    African Journals Online (AJOL)

    Aghomotsegin

    2015-07-29

    Jul 29, 2015 ... comparative inhibitory effects of acetic acid and vanillin on the ... Different concentrations of inhibitors were spiked in the fermentation ... hardwood and municipal solid wastes. ... done at the cost of an extended lag phase and reduces ..... Formation of acetic acid and lactic acid during fermentation and in ...

  5. Exploiting Inhibitory Siglecs to Combat Food Allergies

    Science.gov (United States)

    2017-10-01

    AWARD NUMBER: W81XWH-16-1-0302 TITLE: Exploiting Inhibitory Siglecs to Combat Food Allergies PRINCIPAL INVESTIGATOR: Michael Kulis, Ph.D...CONTRACTING ORGANIZATION: University of North Carolina at Chapel Hill Chapel Hill, NC 27599 REPORT DATES: October 2017 TYPE OF REPORT: Annual PREPARED FOR...Department of Defense, Washington Headquarters Services , Directorate for Information Operations and Reports (0704-0188), 1215 Jefferson Davis Highway, Suite

  6. Large N lattice QCD and its extended strong-weak connection to the hypersphere

    International Nuclear Information System (INIS)

    Christensen, Alexander S.; Myers, Joyce C.; Pedersen, Peter D.

    2014-01-01

    We calculate an effective Polyakov line action of QCD at large N c and large N f from a combined lattice strong coupling and hopping expansion working to second order in both, where the order is defined by the number of windings in the Polyakov line. We compare with the action, truncated at the same order, of continuum QCD on S 1 ×S d at weak coupling from one loop perturbation theory, and find that a large N c correspondence of equations of motion found in http://dx.doi.org/10.1007/JHEP10(2012)067 at leading order, can be extended to the next order. Throughout the paper, we review the background necessary for computing higher order corrections to the lattice effective action, in order to make higher order comparisons more straightforward

  7. Luzindole but not 4-phenyl-2- propionamidotetralin (4P-PDOT) diminishes the inhibitory effect of melatonin on murine Colon 38 cancer growth in vitro.

    Science.gov (United States)

    Winczyk, Katarzyna; Fuss-Chmielewska, Julita; Lawnicka, Hanna; Pawlikowski, Marek; Karasek, Michal

    2009-01-01

    Our earlier studies have shown that MLT exerts the inhibitory effect on murine cancer via membrane and nuclear receptors. We have found that the antagonist of MT1 receptors does not diminish the antiproliferative effect of MLT on Colon 38 cells, and the contribution of MT2 receptors has been suggested to be responsible. Therefore, in the present study we have examined the influence of the 4-phenyl-2-propionamidotetralin (4P-PDOT), which is a selective antagonist of MT2 membrane receptor, and luzindole - an antagonist of both membrane receptors, on an oncostatic action of MLT. The murine cancer cell line Colon 38 was used in the experiments. In 48 hrs cell culture the effects of MLT, 4P-PDOT and luzindole administered alone and MLT applied jointly with either 4P-PDOT or luzindole were examined. The growth of cancer cells was assessed using the modified colorimetric Mosmann method. Melatonin at both examined concentrations (10-7, 10-9 M) significantly decreased the viability of cancer cells. The selective antagonist of MT2 membrane receptor, namely 4P-PDOT and luzindole applied separately did not have an effect on the growth of Colon 38 cells. The addition of 4P-PDOT to MLT did not change the inhibitory effect of MLT, whereas luzindole given together with MLT diminished, but failed to block totally, the oncostatic properties of MLT. The obtained data and our previous studies conducted on Colon 38 cancer indicate that membrane melatonin receptors are not indispensable to the oncostatic action of melatonin and thus other pathways such as nuclear signaling and receptor-independent mechanism may be also involved.

  8. Production of antioxidant and ACE-inhibitory peptides from Kluyveromyces marxianus protein hydrolysates: Purification and molecular docking

    Directory of Open Access Journals (Sweden)

    Mahta Mirzaei

    2018-04-01

    Full Text Available Kluyveromyces marxianus protein hydrolysates were prepared by two different sonicated-enzymatic (trypsin and chymotrypsin hydrolysis treatments to obtain antioxidant and ACE-inhibitory peptides. Trypsin and chymotrypsin hydrolysates obtained by 5 h, exhibited the highest antioxidant and ACE-inhibitory activities. After fractionation using ultrafiltration and reverse phase high performance liquid chromatography (RP-HPLC techniques, two new peptides were identified. One fragment (LL-9, MW = 1180 Da with the amino acid sequence of Leu-Pro-Glu-Ser-Val-His-Leu-Asp-Lys showed significant ACE inhibitory activity (IC50 = 22.88 μM while another peptide fragment (VL-9, MW = 1118 Da with the amino acid sequence of Val-Leu-Ser-Thr-Ser-Phe-Pro-Pro-Lys showed the highest antioxidant and ACE inhibitory properties (IC50 = 15.20 μM, 5568 μM TE/mg protein. The molecular docking studies revealed that the ACE inhibitory activities of VL-9 is due to interaction with the S2 (His513, His353, Glu281 and S′1 (Glu162 pockets of ACE and LL-9 can fit perfectly into the S1 (Thr345 and S2 (Tyr520, Lys511, Gln281 pockets of ACE. Keywords: K. marxianus, Bioactive peptides, Antioxidant, ACE inhibitory, Protein hydrolysate

  9. Structure–Activity Relationship of Oligomeric Flavan-3-ols: Importance of the Upper-Unit B-ring Hydroxyl Groups in the Dimeric Structure for Strong Activities

    Directory of Open Access Journals (Sweden)

    Yoshitomo Hamada

    2015-10-01

    Full Text Available Proanthocyanidins, which are composed of oligomeric flavan-3-ol units, are contained in various foodstuffs (e.g., fruits, vegetables, and drinks and are strongly biologically active compounds. We investigated which element of the proanthocyanidin structure is primarily responsible for this functionality. In this study, we elucidate the importance of the upper-unit of 4–8 condensed dimeric flavan-3-ols for antimicrobial activity against Saccharomyces cerevisiae (S. cerevisiae and cervical epithelioid carcinoma cell line HeLa S3 proliferation inhibitory activity. To clarify the important constituent unit of proanthocyanidin, we synthesized four dimeric compounds, (−-epigallocatechin-[4,8]-(+-catechin, (−-epigallocatechin-[4,8]-(−-epigallocatechin, (−-epigallocatechin-[4,8]-(−-epigallocatechin-3-O-gallate, and (+-catechin-[4,8]-(−-epigallocatechin and performed structure–activity relationship (SAR studies. In addition to antimicrobial activity against S. cerevisiae and proliferation inhibitory activity on HeLa S3 cells, the correlation of 2,2-diphenyl-l-picrylhydrazyl radical scavenging activity with the number of phenolic hydroxyl groups was low. On the basis of the results of our SAR studies, we concluded that B-ring hydroxyl groups of the upper-unit of the dimer are crucially important for strong and effective activity.

  10. Phospho-dependent binding of the clathrin AP2 adaptor complex to GABAA receptors regulates the efficacy of inhibitory synaptic transmission.

    Science.gov (United States)

    Kittler, Josef T; Chen, Guojun; Honing, Stephan; Bogdanov, Yury; McAinsh, Kristina; Arancibia-Carcamo, I Lorena; Jovanovic, Jasmina N; Pangalos, Menelas N; Haucke, Volker; Yan, Zhen; Moss, Stephen J

    2005-10-11

    The efficacy of synaptic inhibition depends on the number of gamma-aminobutyric acid type A receptors (GABA(A)Rs) expressed on the cell surface of neurons. The clathrin adaptor protein 2 (AP2) complex is a critical regulator of GABA(A)R endocytosis and, hence, surface receptor number. Here, we identify a previously uncharacterized atypical AP2 binding motif conserved within the intracellular domains of all GABA(A)R beta subunit isoforms. This AP2 binding motif (KTHLRRRSSQLK in the beta3 subunit) incorporates the major sites of serine phosphorylation within receptor beta subunits, and phosphorylation within this site inhibits AP2 binding. Furthermore, by using surface plasmon resonance, we establish that a peptide (pepbeta3) corresponding to the AP2 binding motif in the GABA(A)R beta3 subunit binds to AP2 with high affinity only when dephosphorylated. Moreover, the pepbeta3 peptide, but not its phosphorylated equivalent (pepbeta3-phos), enhanced the amplitude of miniature inhibitory synaptic current and whole cell GABA(A)R current. These effects of pepbeta3 on GABA(A)R current were occluded by inhibitors of dynamin-dependent endocytosis supporting an action of pepbeta3 on GABA(A)R endocytosis. Therefore phospho-dependent regulation of AP2 binding to GABA(A)Rs provides a mechanism to specify receptor cell surface number and the efficacy of inhibitory synaptic transmission.

  11. Inhibitory effects of 3-bromopyruvate on human gastric cancer implant tumors in nude mice.

    Science.gov (United States)

    Xian, Shu-Lin; Cao, Wei; Zhang, Xiao-Dong; Lu, Yun-Fei

    2014-01-01

    Gastric cancer is a common malignant tumor. Our previous study demonstrated inhibitory effects of 3-bromopyruvate (3-BrPA) on pleural mesothelioma. Moreover, we found that 3-BrPA could inhibit human gastric cancer cell line SGC-7901 proliferation in vitro, but whether similar effects might be exerted in vivo have remained unclear. To investigate the effect of 3-BrPA to human gastric cancer implant tumors in nude mice. Animals were randomly divided into 6 groups: 3-BrPA low, medium and high dose groups, PBS negative control group 1 (PH7.4), control group 2 (PH 6.8-7.8) and positive control group receiving 5-FU. The TUNEL method was used to detect apoptosis, and cell morphology and structural changes of tumor tissue were observed under transmission electron microscopy (TEM). 3-BrPA low, medium, high dose group, and 5-FU group, the tumor volume inhibition rates were 34.5%, 40.2%, 45.1%, 47.3%, tumor volume of experimental group compared with 2 PBS groups (p0.05). TEM showed typical characteristics of apoptosis. TUNEL demonstrated apoptosis indices of 28.7%, 39.7%, 48.7% for the 3-BrPA low, medium, high dose groups, 42.2% for the 5-FU group and 5% and 4.3% for the PBS1 (PH7.4) and PBS2 (PH6.8-7.8) groups. Compared each experimental group with 2 negative control groups, there was significant difference (p0.05), but there was between the 5-FU and high dose groups (p<0.05). This study indicated that 3-BrPA in vivo has strong inhibitory effects on human gastric cancer implant tumors in nude mice .

  12. Macrophage migration inhibitory factor is elevated in obese adolescents

    NARCIS (Netherlands)

    Kamchybekov, Uran; Figulla, Hans R.; Gerdes, Norbert; Jung, Christian

    2012-01-01

    Objectives: The prevalence of obesity in childhood and adolescence is continuing rising. Macrophage migration inhibitory factor (MIF) participates in inflammatory and immune responses as a pro-inflammatory cytokine. The present study aimed to investigate MIF in overweight adolescents. Methods:

  13. A cross-cultural investigation of inhibitory control, generative fluency, and anxiety symptoms in Romanian and Russian preschoolers.

    Science.gov (United States)

    Cheie, Lavinia; Veraksa, Aleksander; Zinchenko, Yuri; Gorovaya, Alexandra; Visu-Petra, Laura

    2015-01-01

    The current study focused on the early development of inhibitory control in 5- to 7-year-old children attending kindergarten in two Eastern-European countries, Romania and Russia. These two countries share many aspects of child-rearing and educational practices, previously documented to influence the development of inhibitory control. Using the Lurian-based developmental approach offered by the Developmental Neuropsychological Assessment battery, the study aimed to contribute to cross-cultural developmental neuropsychology by exploring (a) early interrelationships between subcomponents of inhibitory control (response suppression and attention control) and generative fluency (verbal and figural) in these two cultures, as well as (b) the predictive value of external factors (culture and maternal education) and individual differences (age, gender, nonverbal intelligence, trait anxiety) on inhibitory control and fluency outcomes in children from both countries. First, findings in both culture samples suggest that even at this young age, the construct of inhibitory control cannot be considered a unitary entity. Second, differences in maternal education were not predictive of either inhibitory control or fluency scores. However, children's attention control performance varied as a function of culture, and the direction of these cultural effects differed by whether the target outcome involved performance accuracy versus efficiency as an output. Findings also confirmed the previously documented intensive developmental improvement in preschoolers' inhibitory control during this period, influencing measures of response suppression and particularly attention control. Finally, the results further stress the importance of individual differences effects in trait anxiety on attention control efficiency across cultures.

  14. The Meaning and Organization of Physical Education Teachers' Actions during Conflict with Students.

    Science.gov (United States)

    Flavier, Eric; Bertone, Stefano; Hauw, Denis; Durand, Marc

    2002-01-01

    Used course-of-action theory to identify typical organization of teachers' actions when in conflict with students. Middle school physical educators were interviewed and filmed during lessons. Overall, teacher-student conflicts were infrequent. When conflict occurred, teacher attempts at resolution were under strong time pressure, leading to risk…

  15. Isolation and Characterization of Protein Tyrosine Phosphatase 1B (PTP1B Inhibitory Polyphenolic Compounds From Dodonaea viscosa and Their Kinetic Analysis

    Directory of Open Access Journals (Sweden)

    Zia Uddin

    2018-03-01

    Full Text Available Diabetes mellitus is one of a major worldwide concerns, regulated by either defects in secretion or action of insulin, or both. Insulin signaling down-regulation has been related with over activity of protein tyrosine phosphatase 1B (PTP1B enzyme, which has been a promising target for the treatment of diabetes mellitus. Herein, activity guided separation of methanol extract (95% of Dodonaea viscosa aerial parts afforded nine (1-9 polyphenolic compounds, all of them were identified through spectroscopic data including 2D NMR and HREIMS. Subsequently, their PTP1B inhibitory potentials were evaluated, in which all of the isolates exhibited significant dose-dependent inhibition with IC50 13.5–57.9 μM. Among them, viscosol (4 was found to be the most potent compound having IC50 13.5 μM. In order to unveil the mechanistic behavior, detailed kinetic study was carried out, in which compound 4 was observed as a reversible, and mixed type I inhibitor of PTP1B with inhibitory constant (Ki value of 4.6 μM. Furthermore, we annotated the major metabolites through HPLC-DAD-ESI/MS analysis, in which compounds 3, 6, 7, and 9 were found to be the most abundant metabolites in D. viscosa extract.

  16. Isolation and characterization of protein tyrosine phosphatase 1B (PTP1B) inhibitory polyphenolic compounds from Dodonaea viscosa and their kinetic analysis

    Science.gov (United States)

    Uddin, Zia; Song, Yeong Hun; Ullah, Mahboob; Li, Zuopeng; Kim, Jeong Yoon; Park, Ki Hun

    2018-03-01

    Diabetes mellitus is one of a major worldwide concerns, regulated by either defects in secretion or action of insulin, or both. Insulin signaling down-regulation has been related with over activity of protein tyrosine phosphatase 1B (PTP1B) enzyme, which has been a promising target for the treatment of diabetes mellitus. Herein, activity guided separation of methanol extract (95%) of Dodonaea viscosa aerial parts afforded nine (1-9) polyphenolic compounds, all of them were identified through spectroscopic data including 2D NMR and HREIMS. Subsequently, their PTP1B inhibitory potentials were evaluated, in which all of the isolates exhibited significant dose-dependent inhibition with IC50 13.5-57.9 μM. Among them, viscosol (4) was found to be the most potent compound having IC50 13.5 μM. In order to unveil the mechanistic behavior, detailed kinetic study was carried out, in which compound 4 was observed as a reversible, and mixed type I inhibitor of PTP1B with inhibitory constant (Ki) value of 4.6 μM. Furthermore, we annotated the major metabolites through HPLC-DAD-ESI/MS analysis, in which compounds 3, 6, 7 and 9 were found to be the most abundant metabolites in D.viscosa extract.

  17. Monetary rewards modulate inhibitory control

    Directory of Open Access Journals (Sweden)

    Paula Marcela Herrera

    2014-05-01

    Full Text Available The ability to override a dominant response, often referred to as behavioural inhibiton, is considered a key element of executive cognition. Poor behavioural inhibition is a defining characteristic of several neurological and psychiatric populations. Recently, there has been increasing interest in the motivational dimension of behavioural inhibition, with some experiments incorporating emotional contingencies in classical inhibitory paradigms such as the Go/Nogo and Stop Signal Tasks. Several studies have reported a positive modulatory effect of reward on the performance of such tasks in pathological conditions such as substance abuse, pathological gambling, and ADHD. However, experiments that directly investigate the modulatory effects of reward magnitudes on the performance of inhibitory paradigms are rare and consequently, little is known about the finer grained relationship between motivation and self-control. Here, we probed the effect of reward and reward magnitude on behavioural inhibition using two modified version of the widely used Stop Signal Task. The first task compared no reward with reward, whilst the other compared two different reward magnitudes. The reward magnitude effect was confirmed by the second study, whereas it was less compelling in the first study, possibly due to the effect of having no reward in some conditions. In addition, our results showed a kick start effect over global performance measures. More specifically, there was a long lasting improvement in performance throughout the task, when participants received the highest reward magnitudes at the beginning of the protocol. These results demonstrate that individuals’ behavioural inhibition capacities are dynamic not static because they are modulated by the reward magnitude and initial reward history of the task at hand.

  18. Ultrasonic extraction of polysaccharides from Laminaria japonica and their antioxidative and glycosidase inhibitory activities

    Science.gov (United States)

    Wan, Peng; Yang, Xiaoman; Cai, Bingna; Chen, Hua; Sun, Huili; Chen, Deke; Pan, Jianyu

    2015-08-01

    In the present study, ultrasonic extraction technique (UET) is used to improve the yield of polysaccharides from Laminaria japonica (LJPs). And their antioxidative as well as glycosidase inhibitory activities are investigated. Box-Behnken design (BBD) combined with response surface methodology (RSM) is applied to optimize ultrasonic extraction for polysaccharides. The optimized conditions are obtained as extraction time at 54 min, ultrasonic power at 1050 W, extraction temperature at 80°C and ratio of material to solvent at 1:50 (g mL-1). Under these optimal ultrasonic extraction conditions, an actual experimental yield (5.75% ± 0.3%) is close to the predicted result (5.67%) with no significant difference ( P > 0.05). Vitro antioxidative and glycosidase inhibitory activities tests indicate that the crude polysaccharides (LJP) and two major ethanol precipitated fractions (LJP1 and LJP2) are in a concentration-dependent manner. LJP2 (30%-60% ethanol precipitated polysaccharides) possesses the strongest α-glucosidase inhibitory activity and moderate scavenging activity against hydroxyl radicals (66.09% ± 2.19%, 3.0 mg mL-1). Also, the inhibitory activity against α-glucosidase (59.08% ± 3.79%, 5.0 mg mL-1) is close to that of acarbose (63.99% ± 3.27%, 5.0 mg mL-1). LJP1 (30% ethanol precipitated polysaccharides) exhibits the strongest scavenging activity against hydroxyl radicals (99.80% ± 0.00%, 3.0 mg mL-1) and moderate α-glucosidase inhibitory activity (47.76% ± 1.92%, 5.0 mg mL-1). LJP shows the most remarkable DPPH scavenging activity (66.20% ± 0.11%, 5.0 mg mL-1) but weakest α-glucosidase inhibitory activity (37.77% ± 1.30%, 5.0 mg mL-1). However, all these LJPs exert weak inhibitory effects against α-amylase. These results show that UET is an effective method for extracting bioactive polysaccharides from seaweed materials. LJP1 and LJP2 can be developed as a potential ingredient in hypoglycemic agents or functional food for the management of

  19. Neuroscientific Insights: Attention, Working Memory, and Inhibitory Control

    Science.gov (United States)

    Raver, C. Cybele; Blair, Clancy

    2016-01-01

    In this article, Cybele Raver and Clancy Blair explore a group of cognitive processes called executive function (EF)--including the flexible control of attention, the ability to hold information through working memory, and the ability to maintain inhibitory control. EF processes are crucial for young children's learning. On the one hand, they can…

  20. A tick B-cell inhibitory protein from salivary glands of the hard tick, Hyalomma asiaticum asiaticum

    International Nuclear Information System (INIS)

    Yu Da; Liang Jiangguo; Yu Haining; Wu Haifeng; Xu Chunhua; Liu Jingze; Lai Ren

    2006-01-01

    Some studies done to date suggest that B-cell inhibitory factor occurred in tick saliva. In this study, a novel protein having B-cell inhibitory activity was purified and characterized from the salivary glands of the hard tick, Hyalomma asiaticum asiaticum. This protein was named B-cell inhibitory factor (BIF). The cDNA encoding BIF was cloned by cDNA library screening. The predicted protein from the cDNA sequence is composed of 138 amino acids including the mature BIF. No similarity was found by Blast search. The lipopolysaccharide-induced B-cell proliferation was inhibited by BIF. This is First report of the identification and characterization of B-cell inhibitory protein from tick. The current study facilitates the study of identifying the interaction among tick, Borrelia burgdorferi, the causative agent of Lyme disease, and host

  1. Effect of Bacteriocin-like Inhibitory Substances Produced by Vaginal ...

    African Journals Online (AJOL)

    Reduction of vaginal Lactobacillus population leads to overgrowth of opportunistic organisms such as Streptococcus agalactiae (Group B Streptococcus, GBS), which causes life threatening neonatal infections. The activities of bacteriocin-like inhibitory substances (BLIS) produced by Lactobacillus species isolated from the ...

  2. Inhibitory effects of OK-432 (Picibanil) on cellular proliferation and adhesive capacity of breast carcinoma cells.

    Science.gov (United States)

    Horii, Yoshio; Iino, Yuichi; Maemura, Michio; Horiguchi, Jun; Morishita, Yasuo

    2005-02-01

    We investigated the potent inhibitory effects of OK-432 (Picibanil) on both cellular adhesion and cell proliferation of estrogen-dependent (MCF-7) or estrogen-independent (MDA-MB-231) breast carcinoma cells. Cellular proliferation of both MCF-7 and MDA-MB-231 cells was markedly inhibited in a dose-dependent manner, when the carcinoma cells were exposed to OK-432. Cell attachment assay demonstrated that incubation with OK-432 for 24 h reduced integrin-mediated cellular adhesion of both cell types. However, fluorescence activated cell sorter (FACS) analysis revealed that incubation with OK-432 for 24 h did not decrease the cell surface expressions of any integrins. These results suggest that the binding avidity of integrins is reduced by OK-432 without alteration of the integrin expression. We conclude that OK-432 inhibits integrin-mediated cellular adhesion as well as cell proliferation of breast carcinoma cells regardless of estrogen-dependence, and that these actions of OK-432 contribute to prevention or inhibition of breast carcinoma invasion and metastasis.

  3. Cytokine modulation by glucocorticoids: mechanisms and actions in cellular studies.

    Science.gov (United States)

    Brattsand, R; Linden, M

    1996-01-01

    Glucocorticoids inhibit the expression and action of most cytokines. This is part of the in vivo feed-back system between inflammation-derived cytokines and CNS-adrenal produced corticosteroids with the probable physiological relevance to balance parts of the host defence and anti-inflammatory systems of the body. Glucocorticoids modulate cytokine expression by a combination of genomic mechanisms. The activated glucocorticoid-receptor complex can (i) bind to and inactivate key proinflammatory transcription factors (e.g. AP-1, NF kappa B). This takes place at the promotor responsive elements of these factors, but has also been reported without the presence of DNA; (ii) via glucocorticoid responsive elements (GRE), upregulate the expression of cytokine inhibitory proteins, e.g. I kappa B, which inactivates the transcription factor NF kappa B and thereby the secondary expression of a series of cytokines; (iii) reduce the half-life time and utility of cytokine mRNAs. In studies with triggered human blood mononuclear cells in culture, glucocorticoids strongly diminish the production of the 'initial phase' cytokines IL-1 beta and TNF-alpha and the 'immunomodulatory' cytokines IL-2, IL-3, IL-4, IL-5, IL-10, IL-12 and IFN-gamma, as well as of IL-6, IL-8 and the growth factor GM-CSF. While steroid treatment broadly attenuates cytokine production, it cannot modulate it selectively, e.g. just the TH0, the TH1 or the TH2 pathways. The production of the 'anti-inflammatory' IL-10 is also inhibited. The exceptions of steroid down-regulatory activity on cytokine expression seem to affect 'repair phase' cytokines like TGF-beta and PDGF. These are even reported to be upregulated, which may explain the rather weak steroid dampening action on healing and fibrotic processes. Some growth factors, e.g. G-CSF and M-CSF, are only weakly affected. In addition to diminishing the production of a cytokine, steroids can also often inhibit its subsequent actions. Because cytokines work in

  4. Effect of Jatropha curcas Peptide Fractions on the Angiotensin I-Converting Enzyme Inhibitory Activity

    Directory of Open Access Journals (Sweden)

    Maira R. Segura-Campos

    2013-01-01

    Full Text Available Hypertension is one of the most common worldwide diseases in humans. Angiotensin I-converting enzyme (ACE plays an important role in regulating blood pressure and hypertension. An evaluation was done on the effect of Alcalase hydrolysis of defatted Jatropha curcas kernel meal on ACE inhibitory activity in the resulting hydrolysate and its purified fractions. Alcalase exhibited broad specificity and produced a protein hydrolysate with a 21.35% degree of hydrolysis and 34.87% ACE inhibition. Ultrafiltration of the hydrolysate produced peptide fractions with increased biological activity (24.46–61.41%. Hydrophobic residues contributed substantially to the peptides’ inhibitory potency. The 5–10 and <1 kDa fractions were selected for further fractionation by gel filtration chromatography. ACE inhibitory activity (% ranged from 22.66 to 45.96% with the 5–10 kDa ultrafiltered fraction and from 36.91 to 55.83% with the <1 kDa ultrafiltered fraction. The highest ACE inhibitory activity was observed in F2 ( μg/mL from the 5–10 kDa fraction and F1 ( μg/mL from the <1 kDa fraction. ACE inhibitory fractions from Jatropha kernel have potential applications in alternative hypertension therapies, adding a new application for the Jatropha plant protein fraction and improving the financial viability and sustainability of a Jatropha-based biodiesel industry.

  5. Overcoming the inhibitory effect of serum on lipofection by increasing the charge ratio of cationic liposome to DNA.

    Science.gov (United States)

    Yang, J P; Huang, L

    1997-09-01

    Since cationic liposome was first developed as a lipofection reagent, a drawback has been noted in that the efficiency of lipofection decreases dramatically after addition of serum to the lipofection medium. This drawback hampers the application of cationic liposome for systematic delivery of genes. In the present studies, we found that the effect of serum on DC-chol liposome-mediated lipofection is dependent on the charge ratio of liposome to DNA. Serum inhibited lipofection activity of the lipoplex at low charge ratios, whereas it enhanced the lipofection activity at high charge ratios. This phenomenon was observed using DOTAP/DOPE but not lipofectamine. Measurement of cellular association of DNA showed that serum could reduce the binding of lipoplex to cells at all tested charge ratios, i.e. 0-10.6. Removal of negatively charged proteins from serum by DEAE Sephacel column abolished the inhibitory effect of serum on lipofection. The fraction contained only negatively charged serum proteins which strongly inhibited lipofection at low charge ratios but not at higher charge ratios. Furthermore, preincubation of serum with positively charged polylysine, which neutralized negatively charged serum proteins, eliminated the inhibitory effect of serum on lipofection. In summary, inactivation of cationic liposome by serum is due to negatively charged serum proteins and it can be overcome by increasing charge ratio of cationic liposome-DNA lipoplexes or by neutralizing the serum with polylysine.

  6. Alpha-glucosidase inhibitory effect and inorganic constituents of Phyllanthus amarus Schum. & Thonn. ash

    Directory of Open Access Journals (Sweden)

    Malinee Wongnawa

    2014-10-01

    Full Text Available This study investigated the -glucosidase inhibitory effect and determined the concentration of some inorganic constituents in P. amarus ash. Oral glucose and sucrose tolerance test were performed on normal mice. In vitro -glucosidase inhibitory activity was evaluated by using yeast a-glucosidase. The element concentrations were measured by inductively coupled plasma (ICP spectroscopy. Single oral administration of P. amarus ash did not show antihyperglycemic effect after glucose administration, but decreased blood glucose level after sucrose administration. The ash showed -glucosidase inhibitory activity in vitro with IC50 of 982 mg/mL. The concentrations of K, Ca, Mg, Mn, Fe, Zn, Cu, Pb, Cr, Ni and Co in P. amarus ash were 35049.80±340.64, 3337.24±52.10, 1368.52±13.29, 90.81±1.34, 87.68±1.15, 18.28±0.22, 4.69±0.07, 1.07±0.15, 0.29±0.03, 0.20±0.04 and 0.10±0.02 mg/g, respectively. These results indicate that the antihyperglycemic effect of P. amarus ash might be partly due to the -glucosidase inhibitory activity of the inorganic constituents.

  7. Early Adversity, RSA, and Inhibitory Control: Evidence of Children’s Neurobiological Sensitivity to Social Context

    Science.gov (United States)

    Skowron, Elizabeth A.; Cipriano-Essel, Elizabeth; Gatzke-Kopp, Lisa M.; Teti, Douglas M.; Ammerman, Robert T.

    2014-01-01

    This study examined parasympathetic physiology as a moderator of the effects of early adversity (i.e., child abuse and neglect) on children’s inhibitory control. Children’s respiratory sinus arrhythmia (RSA) was assessed during a resting baseline, two joint challenge tasks with mother, and an individual frustration task. RSA assessed during each of the joint parent–child challenge tasks moderated the effects of child maltreatment (CM) status on children’s independently-assessed inhibitory control. No moderation effect was found for RSA assessed at baseline or in the child-alone challenge task. Among CM-exposed children, lower RSA levels during the joint task predicted the lowest inhibitory control, whereas higher joint task RSA was linked to higher inhibitory control scores that were indistinguishable from those of non-CM children. Results are discussed with regard to the importance of considering context specificity (i.e., individual and caregiver contexts) in how biomarkers inform our understanding of individual differences in vulnerability among at-risk children. PMID:24142832

  8. [The inhibitory effect of decomposed Chinese traditional medicine Chaihu on Coxsackie B virus(CVB3m) replication and its influence on cell activity].

    Science.gov (United States)

    Wang, X; Wang, Y; Liu, F; Wei, K L

    2001-09-01

    To study the anti-Coxsackie B virus (CVB3m) action of Chaihu(XCT) and its decomposed herb soups No.1 and No.2 in vitro, and also their protective effect on cells. The anti CVB3m and cell protection effects of XCT and its decomposed herb soups No.1 and No.2 were observed by the methods of micro-cell culture and neutral red ingestion, taking cytopathic effect and cell activity as judgments of medicine toxicity and virus replication. The non-toxic concentrations of XCTand its decomposed herb soups No.1 and No.2 had no apparent influence on HeLa cell activity, on the contrary, in certain range of concentrations, they could promote cell growth and cell activity. In therapeutic cell group, XCT and its decomposed herb soups No.1 and No.2 all had apparent inhibitory effect on CVB3m replication, especially the decomposed No.1 showing an inhibitory rate of 107.6%. Under the same decomposed No.1 concentration(1.5 mg/ml), the viral inhibitory rate of the preventive therapeutic cell group was much higher than that of the therapeutic cell group, reaching as high as 128.1%. In virus adsorbed cell group, the CVB3m was also obviously inhibited by the XCT and decomposed No.1 and No.2. By comparing the effects on cell protection and virus replication of XCT and its decomposed herb soups No.1 and No.2, it identifies that XCT can protect cells against virus infection and directly kill the CVB3m, this Chinese herb medicine may be applied clinically for preventing and curing of viral myocarditis.

  9. Age Effect on Automatic Inhibitory Function of the Somatosensory and Motor Cortex: An MEG Study

    Directory of Open Access Journals (Sweden)

    Chia-Hsiung Cheng

    2018-03-01

    Full Text Available Age-related deficiency in the top-down modulation of cognitive inhibition has been extensively documented, whereas the effects of age on a bottom-up or automatic operation of inhibitory function were less investigated. It is unknown that whether the older adults (OA’ reduced behavioral performance and neural responses are due to the insufficient bottom-up processes. Compared to behavioral assessments which have been widely used to examine the top-down control of response inhibition, electrophysiological recordings are more suitable to probe the early-stage processes of automatic inhibitory function. Sensory gating (SG, a phenomenon of attenuated neural response to the second identical stimulus in a paired-pulse paradigm, is an indicator to assess automatic inhibitory function of the sensory cortex. On the other hand, electricity-induced beta rebound oscillation in a single-pulse paradigm reflects cortical inhibition of the motor cortex. From the neurophysiological perspective, SG and beta rebound oscillation are replicable indicators to examine the automatic inhibitory function of human sensorimotor cortices. Thus, the present study aimed to use a whole-head magnetoencephalography (MEG to investigate the age-related alterations of SG function in the primary somatosensory cortex (SI and of beta rebound oscillation in the primary motor cortex (MI in 17 healthy younger and 15 older adults. The Stimulus 2/Stimulus 1 (S2/S1 amplitude ratio in response to the paired-pulse electrical stimulation to the left median nerve was used to evaluate the automatic inhibitory function of SI, and the beta rebound response in the single-pulse paradigm was used to evaluate the automatic inhibitory function of MI. Although there were no significant age-related differences found in the SI SG ratios, the MI beta rebound power was reduced and peak latency was prolonged in the OA. Furthermore, significant association between the SI SG ratio and the MI beta rebound

  10. Age Effect on Automatic Inhibitory Function of the Somatosensory and Motor Cortex: An MEG Study

    Science.gov (United States)

    Cheng, Chia-Hsiung; Lin, Mei-Yin; Yang, Shiou-Han

    2018-01-01

    Age-related deficiency in the top-down modulation of cognitive inhibition has been extensively documented, whereas the effects of age on a bottom-up or automatic operation of inhibitory function were less investigated. It is unknown that whether the older adults (OA)’ reduced behavioral performance and neural responses are due to the insufficient bottom-up processes. Compared to behavioral assessments which have been widely used to examine the top-down control of response inhibition, electrophysiological recordings are more suitable to probe the early-stage processes of automatic inhibitory function. Sensory gating (SG), a phenomenon of attenuated neural response to the second identical stimulus in a paired-pulse paradigm, is an indicator to assess automatic inhibitory function of the sensory cortex. On the other hand, electricity-induced beta rebound oscillation in a single-pulse paradigm reflects cortical inhibition of the motor cortex. From the neurophysiological perspective, SG and beta rebound oscillation are replicable indicators to examine the automatic inhibitory function of human sensorimotor cortices. Thus, the present study aimed to use a whole-head magnetoencephalography (MEG) to investigate the age-related alterations of SG function in the primary somatosensory cortex (SI) and of beta rebound oscillation in the primary motor cortex (MI) in 17 healthy younger and 15 older adults. The Stimulus 2/Stimulus 1 (S2/S1) amplitude ratio in response to the paired-pulse electrical stimulation to the left median nerve was used to evaluate the automatic inhibitory function of SI, and the beta rebound response in the single-pulse paradigm was used to evaluate the automatic inhibitory function of MI. Although there were no significant age-related differences found in the SI SG ratios, the MI beta rebound power was reduced and peak latency was prolonged in the OA. Furthermore, significant association between the SI SG ratio and the MI beta rebound power, which was

  11. The effect of whole body irradiation on the action of strong analgesics of mice

    International Nuclear Information System (INIS)

    Cvetkovicj, M.; Milovanovicj, A.; Tanasijevicj, D.

    1987-01-01

    The effect of whole body irradiation of male mice with single doses of 3 and 7 Gy ( 60 Co source) on analgesic action of three morphine-like drugs was studied. Over the first 6 days after irradiation, the analgesic effect of alfentanil and fentanyl was significantly less pronounced in irradiated animals than in control ones. During the subsequent period of 24 days till the end of experiment, the analgesic effect in irradiated animals gradually increased reaching and exceeding the control values. On the contrary, the analgesic effect of butorphanole was less pronounced in irradiated animals than in control ones, although the difference was not significantly. The difference between butorphanole and other two drugs are probably due to chemical structure and the metabolic fate in the body. (author) 8 refs.; 2 figs

  12. Nitric oxide inhibitory substances from Curcuma mangga rhizomes

    Directory of Open Access Journals (Sweden)

    Kanidta Kaewkroek

    2009-08-01

    Full Text Available Curcuma mangga Val. & Zijp. is a member of the Zingiberaceae family commonly grown in Thailand. It is locally known as mango tumeric because of its mango-like smell when the fresh rhizomes are cut. C. mangga is a popular vegetable, the tips of the young rhizomes and shoots are consumed raw with rice. Medicinally, the rhizomes are used as a stomachic and for chest pains, fever, and general debility. It is also used in postpartum care. In the present study, we investigated the anti-inflammatory effect of the extract and compounds from C. mangga rhizomes against lipopolysaccharide (LPS-induced nitric oxide (NO production in RAW 264.7 cell line. From bioassay-guided fractionation, the chloroform fraction exhibited the most potent inhibitory activity with an IC50 value of 2.1 g/ml, followed by the hexane fraction (IC50 = 3.8 g/ml and the ethyl acetate fraction (IC50 = 23.5 g/ml, respectively. Demethoxycurcumin (1 and 3-buten-2-one, 4-[(1R, 4aR, 8aR-decahydro-5, 5, 8a-trimethyl-2-methylene-1-naphthalenyl]-, (3E-rel- (2 were isolated from the chloroform- and hexane fractions, respectively. Bisdemethoxycurcumin (3 whose structure is similar to that of 1 was also tested for NO inhibitory activity. Of the tested compounds, compound 1 exhibited the highest activity with an IC50 value of 12.1 μM, followed by 3(IC50 = 16.9 M and 2 (IC50 = 30.3 M. These results suggest that C. mangga and its compounds exert NO inhibitory activity and have a potential to be developed as a pharmaceutical preparation for treatment of inflammatory-related diseases. Moreover, this is the first report of compound 2 that was isolated from C. mangga rhizomes.

  13. Evaluating the antioxidant and acetylcholinesterase inhibitory activity of three Centaurea species

    Directory of Open Access Journals (Sweden)

    H. Hajimehdipoor

    2014-01-01

    Full Text Available Factors such as oxidative stress and reduced acetylcholine level have been implicated in Alzheimer’s disease (AD pathology and recently there has been a trend towards natural product research to find potential sources of antioxidants and acetylcholinesterase inhibitors in the plants kingdom. Centaurea is a genus with about 500 species world wild, many of them have shown to possess biologic activity; Centaurea albonites, C. aucheri and C. pseudoscabiosa are three species which little investigation has been carried out about their biological properties. In the present study, the antioxidant and acetylcholinesterase inhibitory activity of the above mentioned species have been evaluated. The ability of the total extract and methanol fraction of the plants to scavenge free radicals has been assessed through DPPH radical scavenging assay, and the acetylcholinesterase inhibitory property has been evaluated by Ellman method. The total extract of all species exhibited moderate antioxidant activity whereas the extracts of C. pseudoscabiosa showed the strongest antioxidant property; its total extract also demonstrated the highest acetylcholinesterase inhibitory activity among the evaluated samples (19.2% inhibition. The results suggest the species as potential sources of natural antioxidants which could be focused in future studies of Alzheimer’s disease.

  14. Medicinal Plants and Their Inhibitory Activities against Pancreatic Lipase: A Review

    Directory of Open Access Journals (Sweden)

    Atefehalsadat Seyedan

    2015-01-01

    Full Text Available Obesity is recognized as a major life style disorder especially in developing countries and it is prevailing at an alarming speed in new world countries due to fast food intake, industrialization, and reduction of physical activity. Furthermore, it is associated with a vast number of chronic diseases and disabilities. To date, relatively effective drugs, from either natural or synthetic sources, are generally associated with serious side effects, often leading to cessation of clinical trials or even withdrawal from the market. In order to find new compounds which are more effective or with less adverse effects compared to orlistat, the drug that has been approved for obesity, new compounds isolated from natural products are being identified and screened for antiobesity effects, in particular, for their pancreatic lipase inhibitory effect. Pancreatic lipase inhibitory activity has been extensively used for the determination of potential efficacy of natural products as antiobesity agents. In attempts to identify natural products for overcoming obesity, more researches have been focused on the identification of newer pancreatic lipase inhibitors with less unpleasant adverse effects. In this review, we consider the potential role of plants that have been investigated for their pancreatic lipase inhibitory activity.

  15. Absolute Configurations and NO Inhibitory Activities of Terpenoids from Curcuma longa.

    Science.gov (United States)

    Xu, Jing; Ji, Feifei; Kang, Jing; Wang, Hao; Li, Shen; Jin, Da-Qing; Zhang, Qiang; Sun, Hongwei; Guo, Yuanqiang

    2015-06-24

    Curcuma longa L., belonging to the Zingiberaceae family, is a perennial herb and has been used as a spice and a pigment in the food industry. In the ongoing search for inhibitory reagents of NO production and survey of the chemical composition of natural vegetable foods, the chemical constituents of C. longa used as spice were investigated. This investigation resulted in the isolation of 2 new terpenoids and 14 known analogues. Their structures were established on the basis of the extensive analyses of 1D and 2D NMR spectroscopic data, and the absolute configurations of 1-4 were elucidated by comparison of the calculated and experimental ECD spectra. Among them, compound 1 is a rare norditerpene with an ent-labdane skeleton, and 2 is a skeletally novel sesquiterpene having an eight-membered ring. All of the compounds were found to possess NO inhibitory activities in murine microglial BV-2 cells. The discovery of two new compounds in this chemical investigation further disclosed the chemical composition of C. longa used a food spice, and the bioassay implied that the natural food spice C. longa, containing terpenoids with NO inhibitory activities, may be potentially promotive to human health.

  16. Action potential bursts in central snail neurons elicited by paeonol: roles of ionic currents

    Science.gov (United States)

    Chen, Yi-hung; Lin, Pei-lin; Hsu, Hui-yu; Wu, Ya-ting; Yang, Han-yin; Lu, Dah-yuu; Huang, Shiang-suo; Hsieh, Ching-liang; Lin, Jaung-geng

    2010-01-01

    Aim: To investigate the effects of 2′-hydroxy-4′-methoxyacetophenone (paeonol) on the electrophysiological behavior of a central neuron (right parietal 4; RP4) of the giant African snail (Achatina fulica Ferussac). Methods: Intracellular recordings and the two-electrode voltage clamp method were used to study the effects of paeonol on the RP4 neuron. Results: The RP4 neuron generated spontaneous action potentials. Bath application of paeonol at a concentration of ≥500 μmol/L reversibly elicited action potential bursts in a concentration-dependent manner. Immersing the neurons in Co2+-substituted Ca2+-free solution did not block paeonol-elicited bursting. Pretreatment with the protein kinase A (PKA) inhibitor KT-5720 or the protein kinase C (PKC) inhibitor Ro 31-8220 did not affect the action potential bursts. Voltage-clamp studies revealed that paeonol at a concentration of 500 μmol/L had no remarkable effects on the total inward currents, whereas paeonol decreased the delayed rectifying K+ current (IKD) and the fast-inactivating K+ current (IA). Application of 4-aminopyridine (4-AP 5 mmol/L), an inhibitor of IA, or charybdotoxin 250 nmol/L, an inhibitor of the Ca2+-activated K+ current (IK(Ca)), failed to elicit action potential bursts, whereas tetraethylammonium chloride (TEA 50 mmol/L), an IKD blocker, successfully elicited action potential bursts. At a lower concentration of 5 mmol/L, TEA facilitated the induction of action potential bursts elicited by paeonol. Conclusion: Paeonol elicited a bursting firing pattern of action potentials in the RP4 neuron and this activity relates closely to the inhibitory effects of paeonol on the IKD. PMID:21042287

  17. Dynamic mobility of functional GABAA receptors at inhibitory synapses.

    Science.gov (United States)

    Thomas, Philip; Mortensen, Martin; Hosie, Alastair M; Smart, Trevor G

    2005-07-01

    Importing functional GABAA receptors into synapses is fundamental for establishing and maintaining inhibitory transmission and for controlling neuronal excitability. By introducing a binding site for an irreversible inhibitor into the GABAA receptor alpha1 subunit channel lining region that can be accessed only when the receptor is activated, we have determined the dynamics of receptor mobility between synaptic and extrasynaptic locations in hippocampal pyramidal neurons. We demonstrate that the cell surface GABAA receptor population shows no fast recovery after irreversible inhibition. In contrast, after selective inhibition, the synaptic receptor population rapidly recovers by the import of new functional entities within minutes. The trafficking pathways that promote rapid importation of synaptic receptors do not involve insertion from intracellular pools, but reflect receptor diffusion within the plane of the membrane. This process offers the synapse a rapid mechanism to replenish functional GABAA receptors at inhibitory synapses and a means to control synaptic efficacy.

  18. Clemastine as Antimicrobial Agent: Effectiveness and Mechanism of Action

    Directory of Open Access Journals (Sweden)

    S.Fazli Bazaz

    1991-07-01

    Full Text Available In this investigation, the antimicrobial activity of Clemastine was studied.The Minimum Inhibitory Concentrations (MICs of this drug against some bacteria were determined using tube dilution method.To find out the bactericidal activity of Clemastine, the number of living bacteria in the presence of drug was counted by a culture method (pour plate method. Thereafter, the preservative effectiveness of Clemastine was studied in detail using standard method (USP 1985.The results show a good antibacterial but not antifungal activity."nIn considering the mechanism of action of Clemastine, it can be seen that the drug has some effect on cell membrane permeability and causes leakage of intracellular material including the K+ .Comparing the bactericidal results with the leakage of K+, shows that the leakage may be due to the bactericidal activity of the drug.

  19. The effect of gastric inhibitory polypeptide on intestinal glucose absorption and intestinal motility in mice

    Energy Technology Data Exchange (ETDEWEB)

    Ogawa, Eiichi [Department of Diabetes and Clinical Nutrition, Graduate School of Medicine, Kyoto University (Japan); Hosokawa, Masaya [Department of Diabetes and Clinical Nutrition, Graduate School of Medicine, Kyoto University (Japan); Faculty of Human Sciences, Tezukayama Gakuin University, Osaka (Japan); Harada, Norio; Yamane, Shunsuke; Hamasaki, Akihiro; Toyoda, Kentaro; Fujimoto, Shimpei; Fujita, Yoshihito; Fukuda, Kazuhito [Department of Diabetes and Clinical Nutrition, Graduate School of Medicine, Kyoto University (Japan); Tsukiyama, Katsushi; Yamada, Yuichiro [Department of Diabetes and Clinical Nutrition, Graduate School of Medicine, Kyoto University (Japan); Department of Internal Medicine, Division of Endocrinology, Diabetes and Geriatric Medicine, Akita University School of Medicine, Akita (Japan); Seino, Yutaka [Department of Diabetes and Clinical Nutrition, Graduate School of Medicine, Kyoto University (Japan); Kansai Electric Power Hospital, Osaka (Japan); Inagaki, Nobuya, E-mail: inagaki@metab.kuhp.kyoto-u.ac.jp [Department of Diabetes and Clinical Nutrition, Graduate School of Medicine, Kyoto University (Japan); CREST of Japan Science and Technology Cooperation (JST), Kyoto (Japan)

    2011-01-07

    Research highlights: {yields} Exogenous GIP inhibits intestinal motility through a somatostatin-mediated pathway. {yields} Exogenous GIP inhibits intestinal glucose absorption by reducing intestinal motility. {yields} The GIP-receptor-mediated action in intestine does not involve in GLP-1-mediated pathway. -- Abstract: Gastric inhibitory polypeptide (GIP) is released from the small intestine upon meal ingestion and increases insulin secretion from pancreatic {beta} cells. Although the GIP receptor is known to be expressed in small intestine, the effects of GIP in small intestine are not fully understood. This study was designed to clarify the effect of GIP on intestinal glucose absorption and intestinal motility. Intestinal glucose absorption in vivo was measured by single-pass perfusion method. Incorporation of [{sup 14}C]-glucose into everted jejunal rings in vitro was used to evaluate the effect of GIP on sodium-glucose co-transporter (SGLT). Motility of small intestine was measured by intestinal transit after oral administration of a non-absorbed marker. Intraperitoneal administration of GIP inhibited glucose absorption in wild-type mice in a concentration-dependent manner, showing maximum decrease at the dosage of 50 nmol/kg body weight. In glucagon-like-peptide-1 (GLP-1) receptor-deficient mice, GIP inhibited glucose absorption as in wild-type mice. In vitro examination of [{sup 14}C]-glucose uptake revealed that 100 nM GIP did not change SGLT-dependent glucose uptake in wild-type mice. After intraperitoneal administration of GIP (50 nmol/kg body weight), small intestinal transit was inhibited to 40% in both wild-type and GLP-1 receptor-deficient mice. Furthermore, a somatostatin receptor antagonist, cyclosomatostatin, reduced the inhibitory effect of GIP on both intestinal transit and glucose absorption in wild-type mice. These results demonstrate that exogenous GIP inhibits intestinal glucose absorption by reducing intestinal motility through a somatostatin

  20. The effect of gastric inhibitory polypeptide on intestinal glucose absorption and intestinal motility in mice

    International Nuclear Information System (INIS)

    Ogawa, Eiichi; Hosokawa, Masaya; Harada, Norio; Yamane, Shunsuke; Hamasaki, Akihiro; Toyoda, Kentaro; Fujimoto, Shimpei; Fujita, Yoshihito; Fukuda, Kazuhito; Tsukiyama, Katsushi; Yamada, Yuichiro; Seino, Yutaka; Inagaki, Nobuya

    2011-01-01

    Research highlights: → Exogenous GIP inhibits intestinal motility through a somatostatin-mediated pathway. → Exogenous GIP inhibits intestinal glucose absorption by reducing intestinal motility. → The GIP-receptor-mediated action in intestine does not involve in GLP-1-mediated pathway. -- Abstract: Gastric inhibitory polypeptide (GIP) is released from the small intestine upon meal ingestion and increases insulin secretion from pancreatic β cells. Although the GIP receptor is known to be expressed in small intestine, the effects of GIP in small intestine are not fully understood. This study was designed to clarify the effect of GIP on intestinal glucose absorption and intestinal motility. Intestinal glucose absorption in vivo was measured by single-pass perfusion method. Incorporation of [ 14 C]-glucose into everted jejunal rings in vitro was used to evaluate the effect of GIP on sodium-glucose co-transporter (SGLT). Motility of small intestine was measured by intestinal transit after oral administration of a non-absorbed marker. Intraperitoneal administration of GIP inhibited glucose absorption in wild-type mice in a concentration-dependent manner, showing maximum decrease at the dosage of 50 nmol/kg body weight. In glucagon-like-peptide-1 (GLP-1) receptor-deficient mice, GIP inhibited glucose absorption as in wild-type mice. In vitro examination of [ 14 C]-glucose uptake revealed that 100 nM GIP did not change SGLT-dependent glucose uptake in wild-type mice. After intraperitoneal administration of GIP (50 nmol/kg body weight), small intestinal transit was inhibited to 40% in both wild-type and GLP-1 receptor-deficient mice. Furthermore, a somatostatin receptor antagonist, cyclosomatostatin, reduced the inhibitory effect of GIP on both intestinal transit and glucose absorption in wild-type mice. These results demonstrate that exogenous GIP inhibits intestinal glucose absorption by reducing intestinal motility through a somatostatin-mediated pathway rather