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Sample records for regional acetylcholinesterase activity

  1. Brain regional acetylcholinesterase activity and muscarinic acetylcholine receptors in rats after repeated administration of cholinesterase inhibitors and its withdrawal

    SciTech Connect

    Kobayashi, Haruo . E-mail: hk1664@iwate-u.ac.jp; Suzuki, Tadahiko; Sakamoto, Maki; Hashimoto, Wataru; Kashiwada, Keiko; Sato, Itaru; Akahori, Fumiaki; Satoh, Tetsuo

    2007-03-15

    Activity of acetylcholinesterase (AChE) and specific binding of [{sup 3}H]quinuclidinyl benzilate (QNB), [{sup 3}H]pirenzepine (PZP) and [{sup 3}H]AF-DX 384 to muscarinic acetylcholine receptor (mAChR) preparations in the striatum, hippocampus and cortex of rats were determined 1, 6 and 11 days after the last treatment with an organophosphate DDVP, a carbamate propoxur or a muscarinic agonist oxotremorine as a reference for 7 and 14 days. AChE activity was markedly decreased in the three regions 1 day after the treatment with DDVP for 7 and 14 days with a gradual recovery 6 to 11 days, and much less decreased 1, 6 and 11 days after the treatment with propoxur for 7 days but not for 14 days in the hippocampus and cortex. The binding of [{sup 3}H]-QNB, PZP and AF-DX 384 in the three regions was generally decreased by the treatment with DDVP for 7 and 14 days. Such down-regulations were generally restored 6 or 11 days after the treatment for 7 but not for 14 days. The down-regulation or up-regulation as measured by [{sup 3}H]-QNB, PZP and AF-DX 384 was observed 1, 6 or 11 days after treatment with propoxur for 7 days and/or 14 days. Repeated treatment with oxotremorine produced similar effects except AChE activity to DDVP. These results suggest that repeated inhibition of AChE activity may usually cause down-regulation of mAChRs with some exception in the hippocampus when a reversible antiChE propoxur is injected.

  2. Acetylcholinesterase activity in Clytia hemisphaerica (Cnidaria).

    PubMed

    Denker, Elsa; Chatonnet, Arnaud; Rabet, Nicolas

    2008-09-25

    Cholinesterase activity is known in representatives of all living organisms phyla but the origin of the cholinergic system as known in bilaterian animals is still undeciphered. In particular the implication of cholinesterases in the nervous system of non-bilaterian Metazoa is not well known. We thus chose to investigate this activity in the Clytia hemisphaerica (Cnidaria) medusa. In toto histochemical staining revealed an acetylcholinesterase activity in the tentacle bulbs but not in the nervous system. Sequences homologous to acetylcholinesterase were searched within Clytia ESTs and compared to other sequences found in public databases.

  3. Simultaneous ultrastructural visualization of acetylcholinesterase activity and tritiated norepinephrine uptake in renal nerves

    SciTech Connect

    Barajas, L.; Wang, P.

    1983-02-01

    In this investigation we have combined the methods of ultrastructural demonstration of acetylcholinesterase activity with electron microscopic autoradiography for the demonstration of norepinephrine uptake. The results show electron-dense deposits indicative of acetylcholinesterase activity associated with perivascular axons overlaid by concentrations of silver grains representing exogenous tritiated norepinephrine. Forty-five percent of the intervaricose regions and 19% of the varicosities overlaid by autoradiographic grains showed ''moderate'' amounts of cholinesterase staining. A greater proportion of autoradiographic grains was observed on the varicosities than in the intervaricose regions; however, the amount of acetylcholinesterase activity was greater in the intervaricose regions than in the varicosities. This investigation provides evidence for the presence of periaxonal acetylcholinesterase staining in adrenergic axons in the rat kidney.

  4. Acetylcholinesterase activity in an experimental rat model of Type C hepatic encephalopathy.

    PubMed

    Méndez, Marta; Méndez-López, Magdalena; López, Laudino; Aller, María A; Arias, Jaime; Arias, Jorge L

    2011-05-01

    Patients with liver malfunction often suffer from hepatic encephalopathy, a neurological complication which can affect attention and cognition. Diverse experimental models have been used to study brain alterations that may be responsible for hepatic encephalopathy symptoms. The aim of the study was to determine whether cognitive impairment found in cirrhosis could be due to disturbance of acetylcholinesterase activity. Acetylcholinesterase activity was assessed in the brains of Wistar rats with thioacetamide-induced cirrhosis. The cirrhotic group displayed up-regulation of acetylcholinesterase levels in the entorrhinal cortex, anterodorsal and anteroventral thalamus and accumbens, whereas down-regulation was found in the CA1, CA3 and dentate gyrus of the hippocampus. Our results indicate that the experimental model of hepatic encephalopathy by chronic administration of thioacetamide presents alterations of acetylcholinesterase activity in brain limbic system regions, which play a role in attention and memory.

  5. Lower Acetylcholinesterase Activity among Children Living with Flower Plantation Workers

    PubMed Central

    Suarez-Lopez, Jose R.; Jacobs, David R.; Himes, John H.; Alexander, Bruce H.; Lazovich, DeAnn; Gunnar, Megan

    2012-01-01

    BACKGROUND Children of workers exposed to pesticides are at risk of secondary pesticide exposure. We evaluated the potential for lower acetylcholinesterase activity in children cohabiting with fresh-cut flower plantation workers, which would be expected from organophosphate and carbamate insecticide exposure. Parental home surveys were performed and acetylcholinesterase activity was measured in 277 children aged 4–9 years in the study of Secondary Exposure to Pesticides among Infants, Children and Adolescents (ESPINA). Participants lived in a rural county in Ecuador with substantial flower plantation activity. RESULTS Mean acetylcholinesterase activity was 3.14 U/ml, standard deviation (SD): 0.49. It was lower by 0.09 U/ml (95% confidence interval (CI) −0.19, −0.001) in children of flower workers (57% of participants) than non-flower workers’ children, after adjustment for gender, age, height-for-age, hemoglobin concentration, income, pesticide use within household lot, pesticide use by contiguous neighbors, examination date and residence distance to nearest flower plantation. Using a 4 level polychotomous acetylcholinesterase activity dependent variable, flower worker cohabitation (vs. not) had odds ratio 3.39 (95% CI 1.19, 9.64) for being <15th percentile compared to the highest tertile. Children cohabitating for ≥5 years (vs. never) had OR of 4.11 (95% CI: 1.17, 14.38) of AChE activity within <15th percentile compared to the highest tertile. CONCLUSIONS Cohabitation with a flower worker was related to lower acetylcholinesterase activity in children. This supports the hypothesis that the amount of take-home pesticides from flower workers suffices to decrease acetylcholinesterase activity, with lower activity associated with longer exposure. PMID:22405996

  6. Production of Enzymatically Active Human Acetylcholinesterase in E. Coli

    DTIC Science & Technology

    1993-10-01

    AD-A282 703 lE1l1lm11I AD( CONTRACT NO: DAMD17-90-C-0107 TITLE: PRODUCTION OF ENZYMATICALLY ACTIVE HUMAN ACETYLCHOLINESTERASE IN E . COLI PRINCIPAL...FUNDING NUMBERS Production of Enzymatically Active Human Contract No. Acetylcholinesterase in E . coli DAMD17-90-C-0107 6. AUTHOR(S) M. Gorecki, Ph.D. and M...S493pMFL-52Ser - Run #1 37 Table 8: Summary of reconstitution and purification of rhAChE derived from E . coli S493pMFL-52Ser - Run #2 38 Table 9

  7. Active Acetylcholinesterase Immobilization on a Functionalized Silicon Surface.

    PubMed

    Khaldi, K; Sam, S; Gouget-Laemmel, A C; Henry de Villeneuve, C; Moraillon, A; Ozanam, F; Yang, J; Kermad, A; Ghellai, N; Gabouze, N

    2015-08-04

    In this work, we studied the attachment of active acetylcholinesterase (AChE) enzyme on a silicon substrate as a potential biomarker for the detection of organophosphorous (OP) pesticides. A multistep functionalization strategy was developed on a crystalline silicon surface: a carboxylic acid-terminated monolayer was grafted onto a hydrogen-terminated silicon surface by photochemical hydrosilylation, and then AChE was covalently attached through amide bonds using an activation EDC/NHS process. Each step of the modification was quantitatively characterized by ex-situ Fourier transform infrared spectroscopy in attenuated-total-reflection geometry (ATR-FTIR) and atomic force microscopy (AFM). The kinetics of enzyme immobilization was investigated using in situ real-time infrared spectroscopy. The enzymatic activity of immobilized acetylcholinesterase enzymes was determined with a colorimetric test. The surface concentration of active AChE was estimated to be Γ = 1.72 × 10(10) cm(-2).

  8. Quantitative structure-activity relationships for organophosphates binding to acetylcholinesterase.

    PubMed

    Ruark, Christopher D; Hack, C Eric; Robinson, Peter J; Anderson, Paul E; Gearhart, Jeffery M

    2013-02-01

    Organophosphates are a group of pesticides and chemical warfare nerve agents that inhibit acetylcholinesterase, the enzyme responsible for hydrolysis of the excitatory neurotransmitter acetylcholine. Numerous structural variants exist for this chemical class, and data regarding their toxicity can be difficult to obtain in a timely fashion. At the same time, their use as pesticides and military weapons is widespread, which presents a major concern and challenge in evaluating human toxicity. To address this concern, a quantitative structure-activity relationship (QSAR) was developed to predict pentavalent organophosphate oxon human acetylcholinesterase bimolecular rate constants. A database of 278 three-dimensional structures and their bimolecular rates was developed from 15 peer-reviewed publications. A database of simplified molecular input line entry notations and their respective acetylcholinesterase bimolecular rate constants are listed in Supplementary Material, Table I. The database was quite diverse, spanning 7 log units of activity. In order to describe their structure, 675 molecular descriptors were calculated using AMPAC 8.0 and CODESSA 2.7.10. Orthogonal projection to latent structures regression, bootstrap leave-random-many-out cross-validation and y-randomization were used to develop an externally validated consensus QSAR model. The domain of applicability was assessed by the William's plot. Six external compounds were outside the warning leverage indicating potential model extrapolation. A number of compounds had residuals >2 or <-2, indicating potential outliers or activity cliffs. The results show that the HOMO-LUMO energy gap contributed most significantly to the binding affinity. A mean training R (2) of 0.80, a mean test set R (2) of 0.76 and a consensus external test set R (2) of 0.66 were achieved using the QSAR. The training and external test set RMSE values were found to be 0.76 and 0.88. The results suggest that this QSAR model can be used in

  9. Acetylcholinesterase activity in the cerebrospinal fluid of dogs with seizures.

    PubMed

    Chai, Orit; Sommer, Adi; Zimmerman, Gabriel; Soreq, Hermona; Friedman, Alon; Bdolah-Abram, Tali; Aroch, Itamar; Shamir, Merav H

    2013-10-01

    Recent studies in animal models have focused on the role of cholinergic elements, mainly acetylcholinesterase (AChE) and the 'readthrough' acetylcholinesterase isoform (AChE-R), in seizures. A prospective double-masked study was conducted to assess the activity of AChE and AChE-R in cerebrospinal fluid (CSF) of 26 dogs post-seizure, 28 dogs with intervertebral disc disease (IVDD) and 16 healthy dogs. AChE was also measured in the serum in the post-seizure and IVDD groups. The results showed no significant differences in CSF AChE among the three groups. AChE-R was not detected in any dog and AChE in the serum was similar between groups. This preliminary study provides new information on AChE and AChE-R in the CSF and sera of dogs following naturally-occurring seizures.

  10. Acetylcholinesterase activity in the brain of dystonia musculorum (Dst(dt-J)) mutant mice.

    PubMed

    Clément, C; Lalonde, R; Strazielle, C

    2012-01-01

    The dystonia musculorum (Dst(dt-J)) mutant mouse suffers from severe motor coordination deficits, characterized, among various symptoms, by a spastic ataxia and dystonic movements, indicating central defects in motor structures in addition to dystrophy of peripheral sensory tracts and partial degeneration of spinocerebellar tracts. Neurochemical alterations, notably in dopaminergic and noradrenergic systems, were previously observed in basal ganglia and cerebellum. A quantitative histochemical cartography of brain acetylcholinesterase activity in Dst(dt-J) mutants, in comparison with controls, revealed increases in the neostriatum, the habenula-interpeduncular pathway, the cholinergic pedunculopontine nucleus and its target structures, the thalamus, major regions of the basal ganglia, such as substantia nigra, ventral tegmental area, globus pallidum, and subthalamic nucleus, as well as in associated extrapyramidal regions, such as red nucleus, brainstem reticular formation, and superior colliculus. These acetylcholinesterase changes may play a role in motor deficits, particularly the dystonic symptomatology observed in the mutation.

  11. Induction of plasma acetylcholinesterase activity in mice challenged with organophosphorus poisons

    SciTech Connect

    Duysen, Ellen G.; Lockridge, Oksana

    2011-09-01

    The restoration of plasma acetylcholinesterase activity in mice following inhibition by organophosphorus pesticides and nerve agents has been attributed to synthesis of new enzyme. It is generally assumed that activity levels return to normal, are stable and do not exceed the normal level. We have observed over the past 10 years that recovery of acetylcholinesterase activity levels in mice treated with organophosphorus agents (OP) exceeds pretreatment levels and remains elevated for up to 2 months. The most dramatic case was in mice treated with tri-cresyl phosphate and tri-ortho-cresyl phosphate, where plasma acetylcholinesterase activity rebounded to a level 250% higher than the pretreatment activity. The present report summarizes our observations on plasma acetylcholinesterase activity in mice treated with chlorpyrifos, chlorpyrifos oxon, diazinon, tri-ortho-cresyl phosphate, tri-cresyl phosphate, tabun thiocholine, parathion, dichlorvos, and diisopropylfluorophosphate. We have developed a hypothesis to explain the excess acetylcholinesterase activity, based on published observations. We hypothesize that acetylcholinesterase activity is induced when cells undergo apoptosis and that consequently there is a rise in the level of plasma acetylcholinesterase. - Highlights: > Acetylcholinesterase activity is induced by organophosphorus agents. > AChE induction is related to apoptosis. > Induction of AChE activity by OP is independent of BChE.

  12. Effect of fluorocarbons on acetylcholinesterase activity and some counter measures

    NASA Technical Reports Server (NTRS)

    Young, W.; Parker, J. A.

    1975-01-01

    An isolated vagal sympathetic heart system has been successfully used for the study of the effect of fluorocarbons (FCs) on cardiac performance and in situ enzyme activity. Dichlorodifluoromethane sensitizes this preparation to sympathetic stimulation and to exogenous epinephrine challenge. Partial and complete A-V block and even cardiac arrest have been induced by epinephrine challenge in the FC sensitized heart. Potassium chloride alone restores the rhythmicity but not the normal contractility of the heart in such a situation. Addition of glucose will, however, completely restore the normal function of the heart which is sensitized by dichlorodifluoromethane. The ED 50 values of acetylcholinesterase activity which are used as a measure of relative effectiveness of fluorocarbons are compared with the maximum permissible concentration. Kinetic studies indicate that all the fluorocarbons tested so far are noncompetitive.

  13. Acetylcholinesterase inhibitory activity of uleine from Himatanthus lancifolius.

    PubMed

    Seidl, Cláudia; Correia, Beatriz L; Stinghen, Andréa E M; Santos, Cid A M

    2010-01-01

    Application of acetylcholinesterase (AChE) inhibitors is the primary treatment for Alzheimer's disease. Alkaloids, such as physostigmine, galanthamine, and huperzine A, play an important role as AChE inhibitors. The aim of this work was to evaluate Himatanthus lancifolius (Muell. Arg.) Woodson, a Brazilian species of Apocynaceae, and its main indole alkaloid uleine, in order to identify new AChE inhibitors. The plant fluid extract, fractions, and uleine were tested for AChE inhibitory activity using Ellman's colorimetric method for thin-layer chromatography (TLC), 96-well microplates, and also Marston's TLC colorimetric method. Both TLC assays showed similar results. At 5 mg/mL, the fluid extract inhibited the AChE enzyme by (50.71 +/- 8.2)%. The ethyl acetate fraction exhibited the highest level of AChE inhibition, followed by the dichloromethane fraction. The isolated alkaloid uleine displayed an IC50 value of 0.45 microM.

  14. Unbalanced acetylcholinesterase activity in larynx squamous cell carcinoma.

    PubMed

    Castillo-González, Ana Cristina; Pelegrín-Hernández, Juan Pablo; Nieto-Cerón, Susana; Madrona, Antonio Piñero; Noguera, José Antonio; López-Moreno, María Fuensanta; Rodríguez-López, José Neptuno; Vidal, Cecilio J; Hellín-Meseguer, Diego; Cabezas-Herrera, Juan

    2015-11-01

    Previous reports have demonstrated that a non-neuronal cholinergic system is expressed aberrantly in airways. A proliferative effect is exerted directly by cholinergic agonists through the activation of nicotinic and muscarinic receptors. In cancer, particularly those related with smoking, the mechanism through which tumour cells respond to aberrantly activated cholinergic signalling is a key question. Fifty paired pieces of larynx squamous cell carcinoma and adjacent non-cancerous tissue were compared in terms of their acetylcholinesterase activity (AChE). The AChE activity in non-cancerous tissues (0.248 ± 0.030 milliunits per milligram of wet tissue; mU/mg) demonstrates that upper respiratory tissues express sufficient AChE activity for controlling the level of acetylcholine (ACh). In larynx carcinomas, the AChE activity decreased to 0.157 ± 0.024 mU/mg (p=0.009). Larynx cancer patients exhibiting low ACh-degrading enzymatic activity had a significantly shorter overall survival (p=0.031). Differences in the mRNA levels of alternatively spliced AChE isoforms and molecular compositions were noted between glottic and supraglottic cancers. Our results suggest that the low AChE activity observed in larynx squamous cell carcinoma may be useful for predicting the outcome of patients.

  15. EEG SPECTRA, BEHAVIORAL STATES AND MOTOR ACTIVITY IN RATS EXPOSED TO ACETYLCHOLINESTERASE INHIBITOR CHLORPYRIFOS.

    EPA Science Inventory

    Exposure to organophosphate pesticides (OP) has been associated with sleep disorders: insomnia and ?excessive dreaming'. However neuronal mechanisms of these effects have not been analyzed. OP inhibit acetylcholinesterase activity leading to a hyperativity of the brain cholin...

  16. A microfluidic paper-based device to assess acetylcholinesterase activity.

    PubMed

    Liu, Chunye; Gomez, Frank A

    2017-04-01

    Neurotransmitters play key roles in cell-to-cell communication. These chemical messengers are involved in many functional processes, including growth, reproduction, memory, and behavior. In this communication, we describe a novel microfluidic paper-based analytical device (μPAD) to detect acetylcholinesterase (AChE) activity and inhibitor screening through a colorimetric analysis. The μPAD is easily fabricated via a wax printing process whereby wax is deposited onto the surface of chromatographic paper, and heated to create a hydrophobic barrier. Separate solutions of 5,5'-dithiobis-(2-nitrobenzoic acid) (DTNB) and samples containing AChE and acetylthiocholine iodide (ATC) (or cysteine, Cys), respectively, are directly spotted onto the μPAD. DTNB and AChE/ATC (or Cys) flow towards each other where a reaction occurs to form the yellow colored 2-nitro-5-thiobenzoic acid anion (TNB(2-) ). The device is dried, scanned, and analyzed yielding a linear range of average inverse yellow intensities versus substrate concentration. An IC50 value (0.045 nM) with a known inhibitor, neostigmine bromide (NB), is obtained on the device. μPADs are low cost and easy to fabricate and have great potential to quantify neurotransmitter activity.

  17. Acetylcholinesterase Activity and Neurodevelopment in Boys and Girls

    PubMed Central

    Himes, John H.; Jacobs, David R.; Alexander, Bruce H.; Gunnar, Megan R.

    2013-01-01

    BACKGROUND: Organophosphate exposures can affect children’s neurodevelopment, possibly due to neurotoxicity induced by acetylcholinesterase (AChE) inhibition, and may affect boys more than girls. We tested the hypothesis that lower AChE activity is associated with lower neurobehavioral development among children living in Ecuadorian floricultural communities. METHODS: In 2008, we examined 307 children (age: 4–9 years; 52% male) and quantified AChE activity and neurodevelopment in 5 domains: attention/executive functioning, language, memory/learning, visuospatial processing, and sensorimotor (NEPSY-II test). Associations were adjusted for demographic and socioeconomic characteristics and height-for-age, flower worker cohabitation, and hemoglobin concentration. RESULTS: Mean ± standard deviation AChE activity was 3.14 ± 0.49 U/mL (similar for both genders). The range of scores among neurodevelopment subtests was 5.9 to 10.7 U (standard deviation: 2.6–4.9 U). Girls had a greater mean attention/executive functioning domain score than boys. In boys only, there were increased odds ratios of low (<9th percentile) neurodevelopment among those in the lowest tertile versus the highest tertile of AChE activity (odds ratios: total neurodevelopment: 5.14 [95% confidence interval (CI): 0.84 to 31.48]; attention/executive functioning domain: 4.55 [95% CI: 1.19 to 17.38], memory/learning domain: 6.03 [95% CI: 1.17 to 31.05]) after adjustment for socioeconomic and demographic factors, height-for-age, and hemoglobin. Within these domains, attention, inhibition and long-term memory subtests were most affected. CONCLUSIONS: Low AChE activity was associated with deficits in neurodevelopment, particularly in attention, inhibition, and memory in boys but not in girls. These critical cognitive skills affect learning and academic performance. Added precautions regarding secondary occupational pesticide exposure would be prudent. PMID:24249815

  18. Synthesis and acetylcholinesterase inhibitory activity of polyhydroxylated sulfated steroids: structure/activity studies.

    PubMed

    Richmond, Victoria; Murray, Ana P; Maier, Marta S

    2013-11-01

    Disulfated and trisulfated steroids have been synthesized from cholesterol and their acetylcholinesterase inhibitory activity has been evaluated. In our studies we have found that the activity was not only dependent on the location of the sulfate groups but on their configurations. 2β,3α,6α-trihydroxy-5α-cholestan-6-one trisulfate (18) was the most active steroid with an IC50 value of 15.48 μM comparable to that of 2β,3α-dihydroxy-5α-cholestan-6-one disulfate (1). Both compounds were found to be less active than the reference compound eserine. The butyrylcholinesterase activity of 1 and 18 was one magnitude lower than that against acetylcholinesterase revealing a selective inhibitor profile.

  19. Structure-activity approach in the reactivation of tabun-phosphorylated human acetylcholinesterase with bispyridinium para-aldoximes.

    PubMed

    Kovarik, Zrinka; Calić, Maja; Sinko, Goran; Bosak, Anita

    2007-06-01

    We investigated interactions of bispyridinium para-aldoximes N,N'-(propano)bis(4-hydroxyiminomethyl) pyridinium bromide (TMB-4), N,N'-(ethano)bis(4-hydroxyiminomethyl)pyridinium methanosulphonate (DMB-4), and N,N'-(methano)bis(4-hydroxyiminomethyl)pyridinium chloride (MMB-4) with human erythrocyte acetylcholinesterase phosphorylated by tabun. We analysed aldoxime conformations to determine the flexibility of aldoxime as an important feature for binding to the acetylcholinesterase active site. Tabun-inhibited human erythrocyte acetylcholinesterase was completely reactivated only by the most flexible bispyridinium aldoxime - TMB-4 with a propylene chain between two rings. Shorter linkers than propylene (methylene or ethylene) as in MMB-4 and DMB-4 did not allow appropriate orientation in the active site, and MMB-4 and DMB-4 were not efficient reactivators of tabun-phosphorylated acetylcholinesterase. Since aldoximes are also reversible inhibitors of native acetylcholinesterase, we determined dissociation constants and their protective index against acetylcholinesterase inactivation by tabun.

  20. Preliminary studies of acetylcholinesterase activity in the rat brain using N-phenylferrocenecarboxamide labelled by the technetium-99m.

    PubMed

    Mejri, Najoua; Said, Nadia Malek; Guizani, Sihem; Essouissi, Imen; Saidi, Mouldi

    2013-05-01

    There is currently great interest in developing radiolabeled substrates for acetylcholinesterase that would be useful in the in vivo imaging of patients with Alzheimer's disease. The reduction of acetylcholinesterase (AChE) activity in the brain has been measured in dementia disorders such as Alzheimer's disease and dementia with Lewy bodies using (11)C and (18)F-labeled acetylcholine analogues. Our aim was to develop a new 99mTc-labeled acetylcholine analogue: N-phenylferrocenecarboxamide labelled with technetium-99m (99mTc-TPCC) to study acetylcholinesterase activity. In vivo and in vitro studies demonstrated that the labelled compound was a substrate for acetylcholinesterase. The hydrolytic rate of this substrate was measured and the specificity was evaluated using the inhibitor BW 284 C51. In rat experiments, the 99mTc-TPCC showed desirable properties for studying the acetylcholinesterase in the rat brain: high hydrolytic rate and a moderate specificity of the substrate for acetylcholinesterase.

  1. Synthesis and acetylcholinesterase/butyrylcholinesterase inhibition activity of new tacrine-like analogues.

    PubMed

    Marco, J L; de los Ríos, C; Carreiras, M C; Baños, J E; Badía, A; Vivas, N M

    2001-03-01

    The synthesis and preliminary results for acetylcholinesterase and butyrylcholinesterase inhibition activity of a series of pyrano[2,3-b]quinolines (2, 3) and benzonaphthyridines (5, 6) derivatives are described. These molecules are tacrine-like analogues which have been prepared from readily available polyfunctionalized ethyl [6-amino-5-cyano-4H-pyrans and 6-amino-5-cyanopyridines]-3-carboxylates via Friedlander condensation with selected ketones. These compounds showed moderate acetylcholinesterase inhibition activity, the more potent (2e, 5b) being 6 times less active than tacrine. The butyrylcholinesterase activity of some of these molecules is also discussed.

  2. Buprofezin inhibits acetylcholinesterase activity in B-biotype Bemisia tabaci.

    PubMed

    Cottage, Emma L A; Gunning, Robin V

    2006-01-01

    B-biotype Bemisia tabaci is a severe insect pest worldwide in many ornamental, agricultural, and horticultural industries. Control of this insect is hampered by resistance to many acetylcholinesterase (AChE)-inhibiting insecticides, such as organophosphates and carbamates. Consequently, insect growth regulators such as buprofezin, which act by inhibiting chitin synthesis, are being investigated for use against B-biotype B. tabaci in Australia. This study discusses the effects of buprofezin on B. tabaciAChE.

  3. Acetylcholinesterase-inhibitory activities of the extracts from sponges collected in mauritius waters.

    PubMed

    Beedessee, Girish; Ramanjooloo, Avin; Surnam-Boodhun, Rashmee; van Soest, Rob W M; Marie, Daniel E P

    2013-03-01

    Patients diagnosed with Alzheimer's disease (AD) show a characteristic neurochemical deficit of acetylcholine, especially in the basal forebrains. The use of acetylcholinesterase (AChE) inhibitors to retard the hydrolysis of acetylcholine has been suggested as a promising strategy for AD treatment. In this study, we evaluated the acetylcholinesterase inhibitory (AChEI) activities of 134 extracts obtained from 45 species of marine sponges. Thin-layer chromatography (TLC) and microplate assays reveal potent acetylcholinsterase inhibitory activities of two AcOEt extracts from the sponges Pericharax heteroraphis and Amphimedon navalis PULITZER-FINALI. We further investigated the inhibitory kinetics of the extracts and found them to display mixed competitive/noncompetitive inhibition and associated their inhibitory activity partly to terpenoids. Acetylcholinesterase inhibitors from marine organisms have been rarely studied, and this study demonstrated the potential of marine sponges as a source of pharmaceutical leads against neurodegenerative diseases.

  4. Gastrointestinal acetylcholinesterase activity following endotracheal microinstillation inhalation exposure to sarin in guinea pigs.

    PubMed

    Chanda, Soma; Song, Jian; Rezk, Peter; Sabnekar, Praveena; Doctor, Bhupendra P; Sciuto, Alfred M; Nambiar, Madhusoodana P

    2010-09-06

    The goal of this study was to assess acetylcholinesterase (AChE) inhibition at different regions of the gastrointestinal (GI) tract following inhalation exposure to nerve agent sarin. Seven major regions of the GI tract were removed from saline control animals (n=3) and 677.4 mg/m(3) sarin-exposed animals at 4h (n=4) and 24h (n=4) post-exposure. AChE activity was determined in blood and homogenized tissue supernatant by specific Ellman's assay using Iso-OMPA, a BChE inhibitor, and expressed as activity/optical density of hemoglobin for blood and activity/mg protein for tissues. Our data showed that the AChE activity was significantly decreased for groups both 4h and 24h post-sarin exposure. Among the seven chosen regions of the guinea pig GI tract, duodenum showed the highest AChE activity in control animals. The AChE activity was significantly decreased in the stomach (p=0.03), duodenum (p=0.029), jejunum (p=0.006), and ileum (p=0.006) 4h following sarin exposure. At 24h post-sarin exposure the AChE activity of duodenum (p=0.029) and ileum (p=0.006) was significantly inhibited. Esophagus showed no inhibition following sarin exposure at both 4h and 24h groups. These results suggest that the AChE activity is different in different regions of the GI tract and highest levels of AChE inhibition following sarin exposure were seen in regions exhibiting higher overall AChE activity and cholinergic function.

  5. Acetylcholinesterase inhibitory activity of lycopodane-type alkaloids from the Icelandic Lycopodium annotinum ssp. alpestre.

    PubMed

    Halldorsdottir, Elsa Steinunn; Jaroszewski, Jerzy W; Olafsdottir, Elin Soffia

    2010-02-01

    The aim of this study was to investigate structures and acetylcholinesterase inhibitory activities of lycopodane-type alkaloids isolated from an Icelandic collection of Lycopodium annotinum ssp. alpestre. Ten alkaloids were isolated, including annotinine, annotine, lycodoline, lycoposerramine M, anhydrolycodoline, gnidioidine, lycofoline, lannotinidine D, and acrifoline, as well as a previously unknown N-oxide of annotine. 1H and 13C NMR data of several of the alkaloids were provided for the first time. Solvent-dependent equilibrium constants between ketone and hemiketal form of acrifoline were determined. Conformation of acrifoline was characterized using NOESY spectroscopy and molecular modelling. The isolated alkaloids were evaluated for their in vitro inhibitory activity against acetylcholinesterase and butyrylcholinesterase. Ligand docking studies based on mutated 3D structure of Torpedo californica acetylcholinesterase provided rationale for low inhibitory activity of the isolated alkaloids as compared to huperzine A or B, which are potent acetylcholinesterase inhibitors belonging to the lycodine class. Based on the modelling studies the lycopodane-type alkaloids seem to fit well into the active site gorge of the enzyme but the position of their functional groups is not compatible with establishing strong hydrogen bonding interactions with the amino acid residues that line the binding site. The docking studies indicate possibilities of additional functionalization of the lycopodane skeleton to render potentially more active analogues.

  6. Brain acetylcholinesterase activity in Wistar and August rats with low and high motor activity (a cytochemical study).

    PubMed

    Sergutina, A V; Rakhmanova, V I

    2014-08-01

    Acetylcholinesterase activity was quantitatively evaluated by cytochemical method in brain structures (layers III and V of the sensorimotor cortex, caudate nucleus, nucleus accumbens, hippocampus CA3 field) of August and Wistar rats demonstrating high and low motor activity in the open field test. In August rats, acetylcholinesterase activity in the analyzed brain structures prevailed in animals with high motor activity in comparison with rats with low motor activity. In Wistar rats, the differences between the animals demonstrating high and low motor activity were less pronounced, but varied depending on the experimental series of studies. Comparisons of August rats with low motor activity and Wistar rats with high motor activity (maximum difference of motor function in these animals) revealed significant excess of acetylcholinesterase activity in layer III of the sensorimotor cortex in August rats and no differences in other brain structures of the examined animals.

  7. Antioxidant and anti-acetylcholinesterase activities of extracts from Rapistrum rugosum in Tunisia

    PubMed Central

    Amel, Omri Hichri; Malek, Besbes Hlila; Hichem, Ben Jannet; Ali, Lamari; Mahjoub, Aouni; Boulbaba, Selmi

    2013-01-01

    Objective To investigate the antioxidant potential and anti-acetylcholinesterase activity of Rapistrum rugosum extracts. Methods The crude, ethyl acetate, butanol and water extracts prepared from flowers, roots, stems and leaves of Rapistrum rugosum were tested at 1 mg/mL to determine their total polyphenol content, total flavonoid content and total condensed tannin content. Their antioxidant activity was assessed at different concentrations (0.0312, 0.0625, 0.1250, 0.25, 0.50 and 1.00 mg/mL) by using DPPH, ABTS, reducing power and β-carotene bleAChIng inhibition activity. Anti-acetylcholinesterase activity was also determined. Results The extract of leaves and stems had the highest total phenolic content [(110.45±0.03) mg gallic acid equivalent/g dry weight]. The ethyl acetate extract of flowers had the highest total flavonoid content [(24.62±0.13) mg quercetin equivalent/g dry weight]. The butanolic fraction of flowers had the highest total condensed tannin content [(317.85±0.01) mg catechin equivalent/g dry weight]. The crude extracts of flowers exhibited an interesting antioxidant activity for DPPH assay (93.00±0.01)% at 1 mg/mL. The greatest acetylcholinesterase inhibitory activity (IC50=1.60 mg/mL) was exhibited by the crude extracts from the flowers. Conclusions The results demonstrated that Rapistrum rugosum contains active constituents which possess antioxidant and anti-acetylcholinesterase activities.

  8. Huperzia quadrifariata and Huperzia reflexa alkaloids inhibit acetylcholinesterase activity in vivo in mice brain.

    PubMed

    Konrath, E L; Neves, B M; Passos, C Dos S; Lunardi, P S; Ortega, M G; Cabrera, J L; Gonçalves, C A; Henriques, A T

    2012-11-15

    Huperzine A, a Lycopodium alkaloid produced by Chinese folk herb Huperzia serrata (Lycopodiaceae), has been shown to be a promising agent for the treatment of Alzheimer's disease due to its potent acetylcholinesterase (AChE) activity, as well its efficacy in the treatment of memory of aged patients. Thus, the effects of two Huperzia species of habitats in Brazil (H. quadrifariata and H. reflexa) with described in vitro AChE inhibition activities were studied and their effects on mice brain AChE inhibition were determined after a single intraperitoneal (i.p.) injection. The alkaloid extracts were administered to mice in various doses (10, 1 and 0.5mg/kg) and acetylcholinesterase activity was measured post mortem in two brain areas using the Ellman's colorimetric method. The AChE activity was found to be significantly reduced in both the cortex and hippocampus, although this activity was less potent than that of reference inhibitor huperzine A (0.5mg/kg). Thus, it appears that H. quadrifariata and H. reflexa alkaloid extracts, shown to inhibit acetylcholinesterase in vitro, also have very potent in vivo effects, suggesting that the Huperzia species may still constitute a promising source of compounds with pharmaceutical interest for Alzheimer's disease.

  9. Acetylcholinesterase (AChE) gene modification in transgenic animals: functional consequences of selected exon and regulatory region deletion.

    PubMed

    Camp, Shelley; Zhang, Limin; Marquez, Michael; de la Torre, Brian; Long, Jeffery M; Bucht, Goran; Taylor, Palmer

    2005-12-15

    . delaTorre, P. Taylor, Knockout mice with deletions of alternatively spliced exons of Acetylcholinesterase, in: N.C. Inestrosa, E.O. Campus (Eds.), VII International Meeting on Cholinesterases, Pucon-Chile Cholinesterases in the Second Millennium: Biomolecular and Pathological Aspects. P. Universidad Catholica de Chile-FONDAP Biomedicina, 2004, pp. 43-48; R.Y.Y. Chan, C. Boudreau-Larivière, L.A. Angus, F. Mankal, B.J. Jasmin, An intronic enhancer containing an N-box motif is required for synapse- and tissue-specific expression of the acetylcholinesterase gene in skeletal muscle fibers. Proc. Natl. Acad. Sci. USA 96 (1999) 4627-4632], is also presented. The intronic region was floxed and then deleted by mating with Ella-cre transgenic mice. The deletion of this region produced a dramatic phenotype; a mouse with near normal AChE expression in brain and other CNS tissues, but no AChE expression in muscle. Phenotype and AChE tissue activities are compared with the total AChE knockout mouse [W. Xie, J.A. Chatonnet, P.J. Wilder, A. Rizzino, R.D. McComb, P. Taylor, S.H. Hinrichs, O. Lockridge, Postnatal developmental delay and supersensitivity to organophosphate in gene-targeted mice lacking acetylcholinesterase. J. Pharmacol. Exp. Ther. 293 (3) (2000) 896-902].

  10. Alkaloid profiles and acetylcholinesterase inhibitory activities of Fumaria species from Bulgaria.

    PubMed

    Vrancheva, Radka Z; Ivanov, Ivan G; Aneva, Ina Y; Dincheva, Ivayla N; Badjakov, Ilian K; Pavlov, Atanas I

    2016-01-01

    GC-MS analysis of alkaloid profiles of five Fumaria species, naturally grown in Bulgaria (F. officinalis, F. thuretii, F. kralikii, F. rostellata and F. schrammii) and analysis of acetylcholinesterase inhibitory activity of alkaloid extracts were performed. Fourteen isoquinoline alkaloids were identified, with the principle ones being protopine, cryptopine, sinactine, parfumine, fumariline, fumarophycine, and fumaritine. Protopine contents, defined by HPLC analysis varied between 210.6 ± 8.8 μg/g DW (F. schrammii) and 334.5 ± 7.1 μg/g DW. (F. rostellata). While all of the investigated alkaloid extracts significantly inhibited acetylcholinesterase activity, the F. kralikii demonstrated the highest level of inhibition (IC(50) 0.13 ± 0.01 mg extract/mL).

  11. Acetylcholinesterase activity and antioxidant capacity of zebrafish brain is altered by heavy metal exposure.

    PubMed

    Richetti, S K; Rosemberg, D B; Ventura-Lima, J; Monserrat, J M; Bogo, M R; Bonan, C D

    2011-01-01

    Pollution is a world problem with immeasurable consequences. Heavy metal compounds are frequently found as components of anthropogenic pollution. Here we evaluated the effects of the treatment with cadmium acetate, lead acetate, mercury chloride, and zinc chloride in acetylcholinesterase activity and gene expression pattern, as well as the effects of these treatments in antioxidant competence in the brain of an aquatic and well-established organism for toxicological analysis, zebrafish (Danio rerio, Cyprinidae). Mercury chloride and lead acetate promoted a significant decrease in acetylcholinesterase activity whereas they did not alter the gene expression pattern. In addition, the antioxidant competence was decreased after exposure to mercury chloride. The data presented here allowed us to hypothesize a signal transmission impairment, through alterations in cholinergic transmission, and also in the antioxidant competence of zebrafish brain tissue as some of the several effects elicited by these pollutants.

  12. Antioxidant and anti-acetylcholinesterase activities of extracts and secondary metabolites from Acacia cyanophylla

    PubMed Central

    Ghribia, Lotfi; Ghouilaa, Hatem; Omrib, Amel; Besbesb, Malek; Janneta, Hichem Ben

    2014-01-01

    Objective To investigate the antioxidant potential and anti-acetycholinesterase activity of compounds and extracts from Acacia cyanophylla (A. cyanophylla). Methods Three polyphenolic compounds were isolated from ethyl acetate extract of A. cyanophylla flowers. They have been identified as isosalipurposide 1, quercetin 2 and naringenin 3. Their structures were elucidated by extensive spectroscopic methods including 1D and 2D NMR experiments as well as ES-MS. The prepared extracts and the isolated compounds 1-3 were tested for their antioxidant activity using 1′-1′-diphenylpicrylhydrazyl (DPPH) and 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) scavenging assays and reducing power. They have been also investigated for inhibitory effect against acetylcholinesterase using the microplate assay. Results In the DPPH test, the EtOAc extract of flowers exhibited the highest antioxidant effect (67.26 µg/mL). Isosalipurposide 1 showed a significant antiradical power against DPPH (81.9 µg/mL). All extracts showed a dose-dependent acetylcholinesterase inhibition. In terms of the IC50 value, the butanolic extract (16.03 µg/mL) was the most potent sample. Isosalipurposide 1 was found to be active against AChE with an IC50 value of 52.04 µg/mL. Conclusions The results demonstrated the important antioxidant and anti-acetylcholinesterase activity of pure compounds and extracts from A. cyanophylla. PMID:25183120

  13. Pre-treatment with ebselen and vitamin E modulate acetylcholinesterase activity: interaction with demyelinating agents.

    PubMed

    Mazzanti, Cinthia M; Spanevello, Roselia; Ahmed, Musthaq; Pereira, Luciane B; Gonçalves, Jamile F; Corrêa, Maisa; Schmatz, Roberta; Stefanello, Naiara; Leal, Daniela B R; Mazzanti, Alexandre; Ramos, Adriano T; Martins, Tessie B; Danesi, Cristiane Cademartori; Graça, Dominguita L; Morsch, Vera M; Schetinger, Maria Rosa C

    2009-02-01

    The ethidium bromide (EB) demyelinating model was associated with vitamin E (Vit E) and ebselen (Ebs) treatment to evaluate acetylcholinesterase (AChE) activity in the striatum (ST), hippocampus (HP), cerebral cortex (CC) and erythrocytes. Rats were divided into seven groups: I-Control (saline), II-(canola); III-(Ebs), IV-(Vit E); V-(EB); VI-(EB+Ebs) and VII-(EB+Vit E). At 3 days after the EB injection, AChE activity in the CC and HC was significantly reduced in groups III, IV, V, VI and VII (p<0.05) and in the ST it was reduced in groups III and V (p<0.05) when compared to the control group. At 21 days after the EB injection, AChE activity in the CC was significantly reduced in groups III, IV and V, while in groups VI and VII a significant increase was observed when compared to the control group. In the HC and ST, AChE activity was significantly reduced in groups V, VI and VII when compared to the control group (p<0.05). In the erythrocytes, at 3 days after the EB injection, AChE activity was significantly reduced in groups III, IV, V, VI and VII and at 21 days there was a significant reduction only in groups VI and VII (p<0.05) when compared to the control group. In conclusion, this study demonstrated that Ebs and Vit E interfere with the cholinergic neurotransmission by altering AChE activity in the different brain regions and in the erythrocytes. Furthermore, treatment with Vit E and Ebs protected against the demyelination lesion caused by EB. In this context, we can suggest that ebselen and Vit E should be considered potential therapeutics and scientific tools to be investigated in brain disorders associated with demyelinating events.

  14. Quercetin Improves Neurobehavioral Performance Through Restoration of Brain Antioxidant Status and Acetylcholinesterase Activity in Manganese-Treated Rats.

    PubMed

    Adedara, Isaac A; Ego, Valerie C; Subair, Temitayo I; Oyediran, Oluwasetemi; Farombi, Ebenezer O

    2017-04-01

    The present study investigated the neuroprotective mechanism of quercetin by assessing the biochemical and behavioral characteristics in rats sub-chronically treated with manganese alone at 15 mg/kg body weight or orally co-treated with quercetin at 10 and 20 mg/kg body weight for 45 consecutive days. Locomotor behavior was monitored using video-tracking software during a 10-min trial in a novel environment whereas the brain regions namely the hypothalamus, cerebrum and cerebellum of the rats were processed for biochemical analyses. Results indicated that co-treatment with quercetin significantly (p < 0.05) prevented manganese-induced locomotor and motor deficits specifically the decrease in total distance travelled, total body rotation, maximum speed, absolute turn angle as well as the increase in time of immobility and grooming. The improvement in the neurobehavioral performance of manganese-treated rats following quercetin co-treatment was confirmed by track and occupancy plot analyses. Moreover, quercetin assuaged manganese-induced decrease in antioxidant enzymes activities and the increase in acetylcholinesterase activity, hydrogen peroxide generation and lipid peroxidation levels in the hypothalamus, cerebrum and cerebellum of the rats. Taken together, quercetin mechanisms of ameliorating manganese-induced neurotoxicity is associated with restoration of acetylcholinesterase activity, augmentation of redox status and inhibition of lipid peroxidation in brain of rats.

  15. Effect of thermal stress and water deprivation on the acetylcholinesterase activity of the pig brain and hypophyses

    NASA Astrophysics Data System (ADS)

    Adejumo, D. O.; Egbunike, G. N.

    1988-06-01

    The effects of direct exposure of boars to thermal stress for 1 h daily for 5 days and to acute water deprivation for 24 or 48 h were studied on the acetylcholinesterase (AChE) activity of porcine brain and hypophysial regions. Mean ambient temperatures, respiratory rates and rectal temperatures in the open were significantly higher than inside the pen. Heat stress induced a rise in AChE activities in the pons, cerebellum, amygdala, hippocampus, hypothalamus, mid-brain and medulla oblongata. However, no significant changes were observed in the cerebral cortex, adenohypophysis and neurohypophysis. Water deprivation significantly ( P<0.05) depressed AChE activity to varying extents depending on the duration of water restriction. Thus AChE activity in the amygdala was depressed by water deprivation for 24 h but partially restored at 48 h. The pons and medulla oblongata were comparable to the amygdala in this respect. The adenohypophysis and neurohypophysis were relatively unaffected.

  16. Acetylcholinesterase inhibition and in vitro and in vivo antioxidant activities of Ganoderma lucidum grown on germinated brown rice.

    PubMed

    Hasnat, Abul; Pervin, Mehnaz; Lim, Beong Ou

    2013-06-07

    In this study, the acetylcholinesterase inhibition and in vitro and in vivo antioxidant activities of Ganoderma lucidum grown on germinated brown rice (GLBR) were evaluated. In antioxidant assays in vitro, GLBR was found to have strong metal chelating activity, DPPH, ABTS, hydroxyl and superoxide radical scavenging activity. Cell-based antioxidant methods were used, including lipid peroxidation on brain homogenate and AAPH-induced erythrocyte haemolysis. In antioxidant assays in vivo, mice were administered with GLBR and this significantly enhanced the activities of antioxidant enzymes in the mice sera, livers and brains. The amount of total phenolic and flavonoid compounds were 43.14 mg GAE/g and 13.36 mg CE/g dry mass, respectively. GLBR also exhibited acetylcholinesterase inhibitory activity. In addition, HPLC analyses of GLBR extract revealed the presence of different phenolic compounds. These findings demonstrate the remarkable potential of GLBR extract as valuable source of antioxidants which exhibit interesting acetylcholinesterase inhibitory activity.

  17. Acetylcholinesterase activity in the pons and medulla oblongata of rats after chronic electroconvulsive shock.

    PubMed

    Camarini, R; Benedito, M A

    1997-10-01

    An imbalance between cholinergic and noradrenergic neurotransmission has been proposed for the etiology of affective disorders. According to this hypothesis, depression would be the result of enhanced cholinergic and reduced noradrenergic neurotransmission. Repeated electroconvulsive shock (ECS) is an effective treatment for depression; moreover, in laboratory animals it induces changes in brain noradrenergic neurotransmission similar to those obtained by chronic treatment with antidepressant drugs (down-regulation of beta-adrenergic receptors). The aim of the present study was to determine whether repeated ECS in rats changes acetylcholinesterase (Achase) activity. Achase controls the level of acetylcholine (Ach) in the synaptic cleft and its levels seem to be regulated by the interaction between Ach and its receptor. Thus, a decrease in Achase activity would suggest decreased cholinergic activity. Adult male Wistar rats received one ECS (80 mA, 0.2 s, 60 Hz) daily for 7 days. Control rats were handled in the same way without receiving the shock. Rats were sacrificed 24 h after the last ECS and membrane-bound and soluble Achase activity was assayed in homogenates obtained from the pons and medulla oblongata. A statistically significant decrease in membrane-bound Achase activity (nmol thiocholine formed min-1 mg protein-1) (control 182.6 +/- 14.8, ECS 162.2 +/- 14.2, P < 0.05) and an increase in soluble Achase activity in the medulla oblongata (control 133.6 +/- 4.2, ECS 145.8 +/- 12.3, P < 0.05) were observed. No statistical differences were observed in Achase activity in the pons. Although repeated ECS induced a decrease in membrane-bound Achase activity, the lack of changes in the pons (control Achase activity: total 231.0 +/- 34.5, membrane-bound 298.9 +/- 18.5, soluble 203.9 +/- 30.9), the region where the locus coeruleus, the main noradrenergic nucleus, is located, does not seem to favor the existence of an interaction between cholinergic and noradrenergic

  18. Antioedematogenic activity, acetylcholinesterase inhibition and antimicrobial properties of Jacaranda oxyphylla.

    PubMed

    Pereira, V V; Silva, R R; Dos Santos, M H; Dias, D F; Moreira, M E C; Takahashi, J A

    2016-09-01

    Jacaranda oxyphylla Cham. (Bignoniaceae) is a shrub found in the Brazilian cerrado and used in folk medicine to treat microbial infections. The aim of this study was to carry out a phytochemical screening and evaluate antioedematogenic, antimicrobial and antiacetylcholinesterase properties of J. oxyphylla crude extracts. All extracts analysed showed presence of terpenoids, which are potentially active chemical substances. A high AChE inhibitory activity for hexane extract from leaves and for the extracts from twigs was found. Ethanol extract from leaves of J. oxyphylla showed activity against Gram-positive (Staphylococcus aureus and Bacillus cereus) and Gram-negative (Escherichia coli) bacteria. This extract was also effective in inhibiting the stages of inflammation evaluated. Biological investigation and phytochemical screening of J. oxyphylla extracts provided additional evidence of its traditional medicinal value.

  19. Effect of isoquinoline alkaloids from two Hippeastrum species on in vitro acetylcholinesterase activity.

    PubMed

    Pagliosa, L B; Monteiro, S C; Silva, K B; de Andrade, J P; Dutilh, J; Bastida, J; Cammarota, M; Zuanazzi, J A S

    2010-07-01

    The treatment of neurological disorders and neurodegenerative diseases is related to the levels of acetylcholine (ACh) through the inhibition of acetylcholinesterase (AChE). Galanthamine, an important alkaloid isolated from the Amaryllidaceae family, is approved for the pharmacological treatment of Alzheimer's disease (AD) and acts by inhibiting the acetylcholinesterase (AChE) activity. In the present study, Ellman's method was used to verify the inhibition of AChE activity of some isoquinolines alkaloids such as galanthamine, montanine, hippeastrine and pretazettine. At the concentrations 1mM, 500 microm and 100 microm, galanthamine presented an AChE inhibition higher than 90%. Montanine inhibited, in a dose-dependent manner, more than 50% of the enzyme at 1mM concentration. With the concentrations 500 microm and 100 microm, 30-45% of AChE activity inhibition was detected. The alkaloids hippeastrine and pretazettine presented no significant inhibition of the AChE activity. The results demonstrate that montanine significantly inhibits AChE activity at the tested concentrations, suggesting the necessity of further investigations on this alkaloid use in treating neurological disorders.

  20. Flexibility of active-site gorge aromatic residues and non-gorge aromatic residues in acetylcholinesterase

    SciTech Connect

    Ghattyvenkatakrishna, Pavan K; Uberbacher, Edward C

    2013-01-01

    The presence of an unusually large number of aromatic residues in the active site gorge of acetylcholinesterase has been a topic of great interest. Flexibility of these residues has been suspected to be a key player in controlling ligand traversal in the gorge. This raises the question of whether the over representation of aromatic residues in the gorge implies higher than normal flexibility of those residues. The current study suggests that it does not. Large changes in the hydrophobic cross sectional area due to dihedral oscillations are probably the reason behind their presence in the gorge.

  1. Structure-activity relationship for the reactivators of acetylcholinesterase inhibited by nerve agent VX.

    PubMed

    Kuca, Kamil; Musilek, Kamil; Jun, Daniel; Karasova, Jana; Soukup, Ondrej; Pejchal, Jaroslav; Hrabinova, Martina

    2013-08-01

    Nerve agents such as sarin, VX and tabun are organophosphorus compounds able to inhibit an enzyme acetylcholinesterase (AChE). AChE reactivators and anticholinergics are generally used as antidotes in the case of intoxication with these agents. None from the known AChE reactivators is able to reactivate AChE inhibited by all kinds of nerve agents. In this work, reactivation potency of seventeen structurally different AChE reactivators was tested in vitro and subsequently, relationship between their chemical structure and biological activity was outlined. VX was chosen as appropriate member of the nerve agent family.

  2. Acetylcholinesterase inhibitory activity of pyrrolizidine alkaloids from Echium confusum Coincy.

    PubMed

    Benamar, Houari; Tomassini, Lamberto; Venditti, Alessandro; Marouf, Abderrazak; Bennaceur, Malika; Serafini, Mauro; Nicoletti, Marcello

    2017-06-01

    Four pyrrolizidine alkaloids, namely 7-O-angeloyllycopsamine N-oxide 1, echimidine N-oxide 2, echimidine 3 and 7-O-angeloylretronecine 4, were isolated for the first time from the whole plant ethanolic extract of Echium confusum Coincy, through bioassay-guided approach. Their structures were determined by spectroscopic means. All the isolates compounds showed moderate activities in inhibiting AChE, with IC50 0.276-0.769.

  3. In vivo and in vitro effects of fructose on rat brain acetylcholinesterase activity: an ontogenetic study.

    PubMed

    Guimarães, Carine A; Biella, Mairis S; Lopes, Abigail; Deroza, Pedro F; Oliveira, Mariana B; Macan, Tamires P; Streck, Emilio L; Ferreira, Gustavo C; Zugno, Alexandra I; Schuck, Patrícia F

    2014-12-01

    Increased fructose concentrations are the biochemical hallmark of fructosemia, a group of inherited disorders on the metabolic pathway of this sugar. The main clinical findings observed in patients affected by fructosemia include neurological abnormalities with developmental delay, whose pathophysiology is still undefined. In the present work we investigated the in vitro and in vivo effects of fructose on acetylcholinesterase (AchE) activity in brain structures of developing rats. For the in vitro experiments, fructose was added at increasing concentrations to the incubation medium. It was observed that fructose provoked an inhibition of acetylcholinesterase activity in cerebral cortex of 30-day-old-rats, even at low concentrations (0.1 mM). For the in vivo experiments, rats were killed 1 h after a single fructose administration (5 µmol/g). Control group received the same volume of saline solution. We found that AchE activity was increased in cerebral cortex of 30- and 60-day-old rats receiving fructose administration. Finally, we observed that AchE activity was unaffected by acute fructose administration in cerebral cortex, striatum or hippocampus of 15- and 90-day-old rats. The present data suggest that a disruption in cholinergic homeostasis may be involved in the pathophysiology of brain damage observed in young patients affected by fructosemia.

  4. Highly-substrate active isoenzyme acetylcholinesterase-II, in rosy eye mutant of Aedes aegypti mosquito.

    PubMed

    Mourya, D T; Gokhale, M D; Barde, P V; Deobagkar, D N

    2001-08-01

    Insecticide bioassays were carried out on larvae and adults of rosy eye mutant and wildtype strains of A. aegypti. Both the strains were equally susceptible to DDT, malathion and deltamethrin. Biochemical assays showed an increase in acetylcholinesterase enzyme (AChE) activity in all the stages of mutant strain with both the substrates i.e. acetylthiocholine iodide and S-butyrylthiocholine iodide. However, there was no difference in the percent inhibition of enzyme activity with propoxur in these two strains. Polyacrylamide gel electrophoresis performed in native conditions on the homogenates of adults of rosy eye mosquitoes showed that AChE-II allele was highly active with the substrate acetylthiocholine iodide as compared to wildtype strain. Frequency of the highly active AChE-II allele in the mutant strain was about 68%, whereas it was about 5% in the wildtype strain.

  5. Phytochemicals content, antioxidant activity and acetylcholinesterase inhibition properties of indigenous Garcinia parvifolia fruit.

    PubMed

    Ali Hassan, Siti Hawa; Fry, Jeffrey R; Abu Bakar, Mohd Fadzelly

    2013-01-01

    Garcinia parvifolia belongs to the same family as mangosteen (Garcinia mangostana), which is known locally in Sabah as "asam kandis" or cherry mangosteen. The present study was conducted to determine the phytochemicals content (total phenolic, flavonoid, anthocyanin, and carotenoid content) and antioxidant and acetylcholinesterase inhibition activity of the flesh and peel of G. parvifolia. All samples were freeze-dried and extracted using 80% methanol and distilled water. For the 80% methanol extract, the flesh of G. parvifolia displayed higher phenolic and flavonoid contents than the peel, with values of 7.2 ± 0.3 mg gallic acid equivalent (GAE)/g and 5.9 ± 0.1 mg rutin equivalent (RU)/g, respectively. Anthocyanins were detected in the peel part of G. parvifolia but absent in the flesh. The peel of G. parvifolia displayed higher total carotenoid content as compared to the flesh part with the values of 17.0 ± 0.3 and 3.0 ± 0.0 mg β-carotene equivalents (BC)/100 g, respectively. The free-radical scavenging, ferric reducing, and acetylcholinesterase inhibition effect of the flesh were higher as compared to the peel in both extracts. These findings suggested that the edible part of G. parvifolia fruit has a potential as a natural source of antioxidant and anti-Alzheimer's agents.

  6. Inhibition effect of graphene oxide on the catalytic activity of acetylcholinesterase enzyme.

    PubMed

    Wang, Yong; Gu, Yao; Ni, Yongnian; Kokot, Serge

    2015-11-01

    Variations in the enzyme activity of acetylcholinesterase (AChE) in the presence of the nano-material, graphene oxide (GO), were investigated with the use of molecular spectroscopy UV-visible and fluorescence methods. From these studies, important kinetic parameters of the enzyme were extracted; these were the maximum reaction rate, Vm , and the Michaelis constant, Km . A comparison of these parameters indicated that GO inhibited the catalytic activity of the AChE because of the presence of the AChE-GO complex. The formation of this complex was confirmed with the use of fluorescence data, which was resolved with the use of the MCR-ALS chemometrics method. Furthermore, it was found that the resonance light-scattering (RLS) intensity of AChE changed in the presence of GO. On this basis, it was demonstrated that the relationship between AChE and GO was linear and such models were used for quantitative analyses of GO.

  7. Effects of Green Tea Extract on Learning, Memory, Behavior and Acetylcholinesterase Activity in Young and Old Male Rats

    ERIC Educational Resources Information Center

    Kaur, Tranum; Pathak, C. M.; Pandhi, P.; Khanduja, K. L.

    2008-01-01

    Objective: To study the effects of green tea extract administration on age-related cognition in young and old male Wistar rats. Methods: Young and old rats were orally administered 0.5% green tea extract for a period of eight weeks and were evaluated by passive avoidance, elevated maze plus paradigm and changes in acetylcholinesterase activity.…

  8. Effect of ovariectomy and estrogen supplementation on brain acetylcholinesterase activity and passive-avoidance learning in rats.

    PubMed

    Das, Amitava; Dikshit, Madhu; Srivastava, Shoba R; Srivastava, Umesh K; Nath, Chandishwar

    2002-09-01

    The effect of ovariectomy and estrogen treatment on the brain acetylcholinesterase activity and cognition in rats was investigated in this study. Ovariectomized and nonovariectomized rats were treated subcutaneously with estradiol dipropionate for 8 d. In the single-trial, passive-avoidance test all the groups showed significant learning and retention of memory as evident by the increase in transfer latency time in trial 2 as compared with trial 1. No-transfer response was significantly increased in the estradiol-dipropionate-treated ovariectomized (80%) and nonovariectomized (60%) group as compared with the ovariectomized (30%) group. Specific activity of acetylcholinesterase was assayed spectrophotometrically in salt-soluble and detergent-soluble fractions of various brain areas: frontal cortex, cerebral cortex, striatum, hippocampus and hypothalamus, thalamus, pons, medulla, and cerebellum. The effect of ovariectomy and estradiol dipropionate was varied in both fractions of these brain areas. Estradiol dipropionate treatment could restore the acetylcholinesterase activity to the control level only in the detergent-soluble fraction of hypothalamus and salt-soluble fraction of hypothalamus, thalamus, and medulla in ovariectomized rats. The results indicate that ovariectomy alters acetylcholinesterase activity in the brain areas but not in a uniform manner and affects only qualitative aspects of cognitive function, which could be improved by estrogen supplementation.

  9. Screening the methanol extracts of some Iranian plants for acetylcholinesterase inhibitory activity

    PubMed Central

    Gholamhoseinian, A.; Moradi, M.N.; Sharifi-far, F.

    2009-01-01

    Acetylcholinesterase (AChE) is the main enzyme for the breakdown of acetylcholine. Nowadays, usage of the inhibitors of this enzyme is one of the most important types of treatment of mild to moderate neurodegenerative diseases such as Alzheimer’s disease. Herbal medicines can be a new source of inhibitors of this enzyme. In this study we examined around 100 different plants to evaluate their inhibitory properties for AChE enzyme. Plants were scientifically identified and their extracts were prepared by methanol percolation. Acetylcholinesterase activity was measured using a colorimetric method in the presence or absence of the extracts. Eserine was used as a positive control. Methanol extracts of the Levisticum officinale, Bergeris integrima and Rheum ribes showed more than 50% AChE inhibitory activity. The inhibition kinetics were studied in the presence of the most effective extracts. L. officinale and B. integrima inhibited AChE activity in a non-competitive manner, while R. ribes competitively inhibitied the enzyme as revealed by double-reciprocal Linweaver-Burk plot analysis. Under controlled condition, Km and Vmax values of the enzyme were found to be 9.4 mM and 0.238 mM/min, respectively. However, in the presence of L. officinale, B. integrima, and R. ribes extracts, Vmax values were 0.192, 0.074 and 0.238 mM/min, respectively. Due to the competitive inhibition of the enzyme by R. ribes extract, the Km value of 21.2 mM was obtained. The concentration required for 50% enzyme inhibition (IC50 value) was 0.5, 0.9, and 0.95 mg/ml for the L. officinale, B. integrima and R. ribes extracts, respectively. The IC50 of the eserine was determined to be 0.8 mg/ml. PMID:21589805

  10. Structural and kinetic effects of mobile phone microwaves on acetylcholinesterase activity.

    PubMed

    Barteri, Mario; Pala, Alessandro; Rotella, Simona

    2005-03-01

    The present study provides evidence that "in vitro" simple exposure of an aqueous solution of electric eel acetylcholinesterase (EeAChE; EC 3.1.1.7.) to cellular phone emission alters its enzymatic activity. This paper demonstrates, by combining different experimental techniques, that radio frequency (RF) radiations irreversibly affect the structural and biochemical characteristics of an important CNS enzyme. These results were obtained by using a commercial cellular phone to reproduce the reality of the human exposition. This experimental procedure provided surprising effects collected practically without experimental errors because they were obtained comparing native and irradiated sample of the same enzyme solution. Although these results cannot be used to conclude whether exposure to RF during the use of cellular phone can lead to any hazardous health effect, they may be a significant first step towards further verification of these effects on other "ex vivo" or "in vivo" biological systems.

  11. Alterations in acetylcholinesterase and electrical activity in the nervous system of cockroach exposed to the neem derivative, azadirachtin.

    PubMed

    Shafeek, A; Jaya Prasanthi, R P; Reddy, G Hariprasad; Chetty, C S; Reddy, G Rajarami

    2004-10-01

    Botanical insecticides are relatively safe and biodegradable, and are readily available sources of bioinsecticides. In recent years, the neem derivative, azadirachtin, has been examined as an alternative to synthetic insecticides because of its broad-spectrum insecticidal action. Because many of the natural products and synthetic compounds used in the control of insect pests are known to exhibit electrophysiological effects, in this paper we focused our studies on the alterations in the activity of the enzyme acetylcholinesterase (AChE) and electrical activity in the nervous system of the cockroach, Periplaneta americana, exposed to azadirachtin. Exposure to azadirachtin produced an excitatory effect on spontaneous electrical activity as well as cercal sensory-mediated giant-fiber responses in the cockroach. Topical exposure to sublethal doses of azadirachtin did not result in any significant alterations in the AChE activity in different regions of the nervous system. We suggest that azadirachtin exerts excitatory action on the electrical activity in the nervous system of cockroach by interfering with the ion channels in the nerve membrane, the probable target of several insecticides.

  12. Chlorpyrifos pollution: its effect on brain acetylcholinesterase activity in rat and treatment of polluted soil by indigenous Pseudomonas sp.

    PubMed

    Sharma, Shelly; Singh, Partap Bir; Chadha, Pooja; Saini, Harvinder Singh

    2017-01-01

    The study was aimed to evaluate the levels of chlorpyrifos (CPF) pollution in agricultural soil of Punjab, India, its detrimental effects on acetylcholinesterase (AChE) activity in rat brain and bioremediation of soils polluted with CPF using indigenous and adapted bacterial lab isolate. The analysis revealed that soil samples of Bathinda and Amritsar regions are highly contaminated with chlorpyrifos showing 19 to 175 mg/kg concentrations of CPF. The non-targeted animals may get poisoned with CPF by its indirect dermal absorption, inhalation of toxic fumes and regular consumption of soiled food grains. The study indicated that even the lowermost concentrations of CPF, 19 and 76 mg/kg of soil found in the Amritsar and Bathinda regions respectively can significantly inhibit the AChE activity in rat brain within 24 h of its treatment. This represents the antagonistic effect of CPF on AChE which is a prime neurotransmitter present in all living beings including humans. In light of this, an attempt was made to remediate the polluted soil, a major reservoir of CPF, using Pseudomonas sp. (ChlD), an indigenous bacterial isolate. The culture efficiently degraded 10 to 100 mg/kg chlorpyrifos supplemented in the soil and utilized it as sole source of carbon and energy for its growth. Thus, this study provides a detailed insight regarding the level of CPF pollution in Punjab, its detrimental effects on mammals and bio-based solution to remediate the sites polluted with CPF.

  13. Salivary Acetylcholinesterase Activity Is Increased in Parkinson's Disease: A Potential Marker of Parasympathetic Dysfunction

    PubMed Central

    Fedorova, Tatyana; Knudsen, Cindy Soendersoe; Mouridsen, Kim; Nexo, Ebba; Borghammer, Per

    2015-01-01

    Introduction. Decreased salivary flow and xerostomia are frequent findings in Parkinson's disease (PD), possibly caused by alterations in the parasympathetic tonus. Here we explore salivary acetylcholinesterase (AChE) activity as a potential biomarker in PD. Methods. We measured salivary flow, AChE activity, and total protein concentration in 30 PD patients and 49 healthy controls. We also performed exploratory correlation analyses with disease duration, motor symptom severity, autonomic complaints, and other nonmotor symptoms. Results. PD patients displayed significantly decreased salivary flow rate, significantly increased salivary AChE activity, and total protein concentration. Importantly, the AChE activity/total protein ratio was significantly increased in PD patients, suggesting that increased AChE activity cannot be explained solely by upconcentration of saliva. The Unified PD Rating Scale (UPDRS) score displayed significant correlation with total salivary protein (P = 0.002) and near-significant correlation with salivary flow (P = 0.07). Color vision test scores were also significantly correlated with AChE activity (P = 0.04) and total protein levels (P = 0.002). Conclusion. Salivary AChE activity is increased in PD patients compared to healthy controls. Future studies are needed to elucidate whether this parameter reflects the extent of neuronal damage and parasympathetic denervation in the salivary glands of PD patients. PMID:25767737

  14. Effect of carbaryl (carbamate insecticide) on acetylcholinesterase activity of two strains of Daphnia magna (Crustacea, Cladocera).

    PubMed

    Toumi, Hela; Bejaoui, Mustapha; Touaylia, Samir; Burga Perez, Karen F; Ferard, Jean François

    2016-11-01

    The present study was designed to investigate the effect of carbaryl (carbamate insecticide) on the acetylcholinesterase activity in two strains (same clone A) of the crustacean cladoceran Daphnia magna. Four carbaryl concentrations (0.4, 0.9, 1.8 and 3.7 µg L(-1)) were compared against control AChE activity. Our results showed that after 48 h of carbaryl exposure, all treatments induced a significant decrease of AChE activities whatever the two considered strains. However, different responses were registered in terms of lowest observed effect concentrations (LOEC: 0.4 µg L(-1) for strain 1 and 0.9 µg L(-1) for strains 2) revealing differences in sensitivity among the two tested strains of D. magna. These results suggest that after carbaryl exposure, the AChE activity responses can be also used as a biomarker of susceptibility. Moreover, our results show that strain1 is less sensitive than strain 2 in terms of IC50-48 h of AChE activity. Comparing the EC50-48 h of standard ecotoxicity test and IC50-48 h of AChE inhibition, there is the same order of sensitivity with both strains.

  15. Chemical composition, aroma evaluation, and inhibitory activity towards acetylcholinesterase of essential oils from Gynura bicolor DC.

    PubMed

    Miyazawa, Mitsuo; Nakahashi, Hiroshi; Usami, Atsushi; Matsuda, Naoki

    2016-04-01

    The compositions of the essential oils obtained from leaves and stems of Gynura bicolor DC. were analyzed by GC-MS. One hundred eight components of these oils were identified. (E)-β-caryophyllene (31.42 %), α-pinene (17.11 %), and bicyclogermacrene (8.09 %) were found to be the main components of the leaf oil, while α-pinene (61.42 %), β-pinene (14.39 %), and myrcene (5.10 %) were the major constituents of the stem oil. We found 73 previously unidentified components in these oils from G. bicolor. The oils were also subjected to odor evaluation. Eleven and 12 aroma-active compounds were detected in the leaf and stem oils, respectively. The abilities of these oils to inhibit acetylcholinesterase (AChE) activity were determined. The sesquiterpenoids in the oils were found to inhibit AChE activity more strongly than the monoterpenoids in the oils did. It was suggested that the three main components in each essential oil act synergistically against AChE activity. These results show that the essential oils obtained from G. bicolor are a good dietary source of AChE activity inhibition.

  16. Influence of water temperature on acetylcholinesterase activity in the pacific tree frog (Hyla regilla)

    USGS Publications Warehouse

    Johnson, Catherine S.; Schwarzbach, Steven E.; Henderson, John D.; Wilson, Barry W.; Tjeerdema, Ronald S.

    2005-01-01

    This investigation evaluated whether acetylcholinesterase (AChE) in Pacific tree frogs (Hyla regilla) from different geographical locations was influenced by different temperatures during early aquatic life stages, independent of pesticide exposure. Tadpoles were collected from both a California coastal pond and a Sierra Nevada mountain range pond, USA. Groups of frogs from each location were raised in temperatures representative of either the Sierra Nevada (8°C) or the coastal (19°C) location. Metamorphs from both locations raised as tadpoles at 19°C had AChE activities of 42.3 and 38.7 nm/min/mg protein, while those raised as tadpoles at 8°C had activities of 26.9 and 28.2 nm/min/mg protein. A two-way analysis of variance revealed temperature to be the significant factor in determining AChE activity (F = 22.3, p < 0.001), although origin was not important (F = 0.09, p = 0.75). Interpretations regarding the influence of pesticides upon AChE activity in Pacific tree frogs must consider the influence of environmental temperature to enable cross-population comparisons.

  17. Synaptosomal acetylcholinesterase activity variation pattern in the presence of electromagnetic fields.

    PubMed

    Afrasiabi, Ali; Riazi, Gholam Hossein; Abbasi, Shayan; Dadras, Ali; Ghalandari, Behafarid; Seidkhani, Hossein; Modaresi, Seyed Mohamad Sadegh; Masoudian, Neda; Amani, Amir; Ahmadian, Shahin

    2014-04-01

    Acetylcholinesterase (AChE) is the enzyme that controls the acetylcholine (ACh) concentrations in cholinergic synaptic clefts by hydrolyzing ACh to choline and acetate. Cholinergic synapses are involved in important functions such as learning, memory and cognition. In this study, we investigated the effects of a wide range of extremely low frequency electromagnetic fields (ELF-EMFs) on synaptic ACh concentrations through AChE enzyme activity assay. Synaptosome suspensions were prepared as a neural terminus from cerebral cortex of sheep brain. Prepared synaptosomes were exposed to ELF-EMFs with frequency ranging from 50 Hz to 230 Hz for duration between 15 and 120 min and flux intensity between 0.1 mT and 1.7 mT. Consequently, AChE activity was measured by Ellman method. Raw data were analyzed by neural network based software, Inform 4.02, to predict AChE activity pattern through nine 3D curves. These curves showed that AChE activity decreases when exposed to ELF-EMFs of 1.2 mT to 1.7 mT intensity and 50 Hz to 90 Hz frequency. Thus, it is proposed that exposure to fields of in this range of frequency-intensity would be effective in clinical treatments of cholinergic disorders to increase synaptic ACh concentration. However, more in vivo experiments are needed to develop this suggested treatment.

  18. A computational insight into acetylcholinesterase inhibitory activity of a new lichen depsidone.

    PubMed

    Ece, Abdulilah; Pejin, Boris

    2015-01-01

    Acetylcholinesterase (AChE) inhibitors are yet the best drugs currently available for the management of Alzheimer's disease. The recent phytochemical investigation has led to the isolation of a new depsidone 1 with moderate AChE activity (1 μg). This work was focused on its electronic properties analysed using commercially available programs. Both the active depsidone molecule 1 and galanthamine showed to have higher HOMO energies than the inactive depsidones 2-4, isolated from the same lichen species. However, the amino depsidone derivative 7, whose structure was proposed using computational approaches, is expected to be more active AChE inhibitor than the depsidone 1, due to the improved HOMO energy value. In addition, the molecular docking study indicated that the compound 7 has ability to make the well-known interactions of potent AChE inhibitors with the enzyme active site. The data presented herein support the design of novel AChE inhibitors based on the depsidone scaffold.

  19. Calcium-activated butyrylcholinesterase in human skin protects acetylcholinesterase against suicide inhibition by neurotoxic organophosphates

    SciTech Connect

    Schallreuter, Karin U.; University of Bradford ). E-mail: K.Schallreuter@bradford.ac.uk; Gibbons, Nicholas C.J.; Elwary, Souna M.; Parkin, Susan M.; Wood, John M.

    2007-04-20

    The human epidermis holds an autocrine acetylcholine production and degradation including functioning membrane integrated and cytosolic butyrylcholinesterase (BuchE). Here we show that BuchE activities increase 9-fold in the presence of calcium (0.5 x 10{sup -3}M) via a specific EF-hand calcium binding site, whereas acetylcholinesterase (AchE) is not affected. {sup 45}Calcium labelling and computer simulation confirmed the presence of one EF-hand binding site per subunit which is disrupted by H{sub 2}O{sub 2}-mediated oxidation. Moreover, we confirmed the faster hydrolysis by calcium-activated BuchE using the neurotoxic organophosphate O-ethyl-O-(4-nitrophenyl)-phenylphosphonothioate (EPN). Considering the large size of the human skin with 1.8 m{sup 2} surface area with its calcium gradient in the 10{sup -3}M range, our results implicate calcium-activated BuchE as a major protective mechanism against suicide inhibition of AchE by organophosphates in this non-neuronal tissue.

  20. Effect of pesticide exposure on acetylcholinesterase activity in subsistence farmers from Campeche, Mexico.

    PubMed

    Rendón von Osten, Jaime; Epomex, Centro; Tinoco-Ojanguren, Rolando; Soares, Amadeu M V M; Guilhermino, Lucia

    2004-08-01

    The authors surveyed agricultural production methods and pesticide use among subsistence farmers (campesinos) in 4 rural communities of Campeche, Mexico. Self-reports of symptoms of poisoning resulting from occupational pesticide exposure were elicited by questionnaire (N = 121), and acetylcholinesterase (AChE) activity during insecticide use was evaluated from blood samples (N = 127). In individuals from 2 of the 4 communities, AChE activity was significantly lower (p < 0.05) than the mean of activity determined for individuals in a reference group. Results of this study show that erythrocyte AChE inhibition provides a good biomarker of exposure to organophosphate pesticides in field studies with human populations. Carbamates, particularly carbofuran, seem to be more associated with exuberant and diversified symptomatology of pesticide exposure than organophosphates. Studies in field communities where both carbamates and organophosphates are suspected to exist should include blood AChE determinations, symptomatology surveys, and socioeconomic questionnaires. The authors recommend that the Mexican National Health Ministry authorities specify additional provisions regarding the use of protective equipment and the adoption of other safety practices during field work, increase information campaigns about the risks of pesticide use and the value of safety practices, and increase programs of medical monitoring and assistance for rural communities dealing with pesticides.

  1. Acetylcholinesterase activity in the erythrocytes of newborn infants with hyperbilirubinemia and asphyxia.

    PubMed

    Mydlil, V; Tomasová, H; Cápová, E; Cerná, M

    1976-01-01

    The authors measured erythrocyte acetylcholinesterase (ACHE) activity in 51 physiologic newborn infants, 35 pregnant women and 101 infants with hyperbilirubinemia caused by hemolytic diseases in the ABO and Rh systems, or of other origin (6 children). In total, 374 examinations of erythrocyte ACHE were performed. The normal values of physiologic infants during the first hours of life were 0.162 +/- 0.03, at the age of 3 days 0.104 +/- 0.04. The values in pregnant women were 0.206 +/- 0.07. The ACHE activity was considerably decreased in newborn infants affected by erythroblastosis-ABO, and its mean value, in the case of exsanguinotransfusion indicated by the Polácek scheme, amounted to 0.060 +/- 0.051. It raised after exsanguinotransfusion and was equal to the value of red cells transfused. In newborn infants affected by erythroblastosis-Rh, the value decreased in the cases complicated with asphyxia. Low values of ACHE are sometimes found in certain cases of IRDS or of septicemia. The determination of erythrocyte ACHE activity enables assessing the state of red blood cells.

  2. Alkaloids from Peumus boldus and their acetylcholinesterase, butyrylcholinesterase and prolyl oligopeptidase inhibition activity.

    PubMed

    Hošt'álková, Anna; Opletal, Lubomír; Kuneš, Jiří; Novák, Zdeněk; Hrabinová, Martina; Chlebek, Jakub; Čegan, Lukáš; Cahlíková, Lucie

    2015-04-01

    Eleven isoquinoline alkaloids (1-11) were isolated from dried leaves of Peumus boldus Mol. by standard chromatographic methods. The chemical structures were elucidated by MS, and 1D and 2D NMR spectroscopic analysis, and by comparison with literature data. Compounds isolated in sufficient amount were evaluated for their acetylcholinesterase, and butyrylcholinesterase inhibition activity using Ellman's method. In the prolyl oligopeptidase assay, Z-Gly-Pro-p-nitroanilide was used as substrate. Promising butyrylcholinesterase inhibition activities were demonstrated by two benzylisoquinoline alkaloids, reticuline (8) and N-methylcoclaurine (9), with IC50 values of 33.6 ± 3.0 µM and 15.0 ± 1.4 µM, respectively. Important prolyl oligopeptidase inhibition activities were shown by N-methyllaurotetanine (6) and sinoacutine (4) with IC50 values of 135.4 ± 23.2 µM and 143.1 ± 25.4 µM, respectively. Other tested compounds were considered inactive.

  3. Acetylcholinesterase inhibitory activity of Thai traditional nootropic remedy and its herbal ingredients.

    PubMed

    Tappayuthpijarn, Pimolvan; Itharat, Arunporn; Makchuchit, Sunita

    2011-12-01

    The incidence of Alzheimer disease (AD) is increasing every year in accordance with the increasing of elderly population and could pose significant health problems in the future. The use of medicinal plants as an alternative prevention or even for a possible treatment of the AD is, therefore, becoming an interesting research issue. Acetylcholinesterase (AChE) inhibitors are well-known drugs commonly used in the treatment of AD. The aim of the present study was to screen for AChE inhibitory activity of the Thai traditional nootropic recipe and its herbal ingredients. The results showed that ethanolic extracts of four out of twenty-five herbs i.e. Stephania pierrei Diels. Kaempfera parviflora Wall. ex Baker, Stephania venosa (Blume) Spreng, Piper nigrum L at 0.1 mg/mL showed % AChE inhibition of 89, 64, 59, 50; the IC50 were 6, 21, 29, 30 microg/mL respectively. The other herbs as well as combination of the whole recipe had no synergistic inhibitory effect on AChE activity. However some plants revealed antioxidant activity. More research should have be performed on this local wisdom remedy to verify the uses in scientific term.

  4. Effect of glyphosate-based herbicide on acetylcholinesterase activity in tadpoles, Hoplobatrachus rugulosus.

    PubMed

    Ruamthum, W; Visetson, S; Milne, J R; Bullangpoti, V

    2011-01-01

    This study focused on the effects of a glyphosate-based herbicide on activity of the neuron enzyme, acetylcholinesterase (AchE), in the tadpole stage (stage 35-39) of the East Asian Bullfrog, Hoplobatrachus rugulosus. There were 4 herbicide concentration treatments consisting of glyphosate-based herbicide added at 21, 24, 27 and 30 microl to 1L de-chlorinated water in glass containers (10x15x20 cm). There were 4 replicates per treatment, each replicate using 20 tadpoles. The toxicity results were compared with tadpoles in distilled water as a control treatment. After 24, 48, 72 and 96 hours exposure to glyphosate-based herbicide concentrations, LC50 values of 25.21, 24.66, 24.16 and 23.63 microl/L, respectively, were recorded. AChE activities decreased significantly and markedly with herbicide concentration. Such inhibition of AChE activity by this glyphosate-based herbicide indicates the potential of such herbicides to disrupt ecological communities in water near where the herbicides are applied.

  5. Novel polyacetylene derivatives and their inhibitory activities on acetylcholinesterase obtained from Panax ginseng roots.

    PubMed

    Murata, Kazuya; Iida, Daiki; Ueno, Yoshihiro; Samukawa, Keiichi; Ishizaka, Toshihiko; Kotake, Takeshi; Matsuda, Hideaki

    2017-01-01

    In our research program to identify cholinesterase and β-secretase inhibitors, we investigated Ginseng (root of Panax ginseng), a crude drug described as a multifunctional drug in the ancient Chinese herbal book Shennong Ben Cao Jing. Results from hexane and methanol extracts showed moderate inhibitory activities. This suggests that ginseng roots may be effective for the prevention of and therapy for dementia. We then focused on hexane extracts of raw ginseng root and dried ginseng root since the determination of hexane extract constituents has not been studied extensively. Activity-guided fractionation and purification led to the isolation of 4 polyacetylene compounds; homopanaxynol, homopanaxydol, (9Z)-heptadeca-1, 9-diene-4,6-diyn-3-one, and (8E)-octadeca-1,8-diene-4,6-diyn-3,10-diol. The chemical structures of these compounds, including stereochemistry, were determined. This is the first study to identify the structure of homopanaxynol and homopanaxydol. Moreover, the modes of action of some compounds were characterized as competitive inhibitors. This study showed, for the first time, that polyacetylene compounds possess acetylcholinesterase inhibitory activities.

  6. Circannual rhythms of acetylcholinesterase (AChE) activity in the freshwater fish Cnesterodon decemmaculatus.

    PubMed

    Menéndez-Helman, Renata J; Ferreyroa, Gisele V; dos Santos Afonso, Maria; Salibián, Alfredo

    2015-01-01

    The use of biomarkers as a tool to assess responses of organisms exposed to pollutants in toxicity bioassays, as well as in aquatic environmental risk assessment protocols, requires the understanding of the natural fluctuation of the particular biomarker. The aim of this study was to characterize the intrinsic variations of acetylcholinesterase (AChE) activity in tissues of a native freshwater teleost fish to be used as biomarker in toxicity tests, taking into account both seasonal influence and fish size. Specific AChE activity was measured by the method of Ellman et al. (1961) in homogenates of fish anterior section finding a seasonal variability. The highest activity was observed in summer, decreasing significantly below 40% in winter. The annual AChE activity cycle in the anterior section was fitted to a sinusoidal function with a period of 11.2 months. Moreover, an inverse relationship between enzymatic activity and the animal size was established. The results showed that both the fish length and seasonal variability affect AChE activity. AChE activity in fish posterior section showed a similar trend to that in the anterior section, while seasonal variations of the activity in midsection were observed but differences were not statistically significant. In addition, no relationship between AChE and total tissue protein was established in the anterior and posterior sections suggesting that the circannual rhythms observed are AChE-specific responses. Results highlight the importance of considering both the fish size and season variations to reach valid conclusions when AChE activity is employed as neurotoxicity biomarker.

  7. The effect of aspartame metabolites on human erythrocyte membrane acetylcholinesterase activity.

    PubMed

    Tsakiris, Stylianos; Giannoulia-Karantana, Aglaia; Simintzi, Irene; Schulpis, Kleopatra H

    2006-01-01

    Studies have implicated aspartame (ASP) with neurological problems. The aim of this study was to evaluate acetylcholinesterase (AChE) activity in human erythrocyte membranes after incubation with the sum of ASP metabolites, phenylalanine (Phe), methanol (met) and aspartic acid (aspt), or with each one separately. Erythrocyte membranes were obtained from 12 healthy individuals and were incubated with ASP hydrolysis products for 1 h at 37 degrees C. AChE was measured spectrophotometrically. Incubation of membranes with ASP metabolites corresponding with 34 mg/kg, 150 mg/kg or 200 mg/kg of ASP consumption resulted in an enzyme activity reduction by -33%, -41%, and -57%, respectively. Met concentrations 0.14 mM, 0.60 mM, and 0.80 mM decreased the enzyme activity by -20%, -32% or -40%, respectively. Aspt concentrations 2.80 mM, 7.60 mM or 10.0 mM inhibited membrane AChE activity by -20%, -35%, and -47%, respectively. Phe concentrations 0.14 mM, 0.35 mM or 0.50mM reduced the enzyme activity by -11%, -33%, and -35%, respectively. Aspt or Phe concentrations 0.82 mM or 0.07 mM, respectively, did not alter the membrane AChE activity. It is concluded that low concentrations of ASP metabolites had no effect on the membrane enzyme activity, whereas high or toxic concentrations partially or remarkably decreased the membrane AChE activity, respectively. Additionally, neurological symptoms, including learning and memory processes, may be related to the high or toxic concentrations of the sweetener metabolites.

  8. acetylcholinesterase inhibitory potential and insecticidal activity of an endophytic Alternaria sp. from Ricinus communis.

    PubMed

    Singh, Bahaderjeet; Thakur, Abhinay; Kaur, Sanehdeep; Chadha, B S; Kaur, Amarjeet

    2012-11-01

    Keeping in view the vast potential of endophytic fungi to produce bioactive molecules, this study aimed at isolating and screening endophytes for the production of acetylcholinesterase inhibitors. Fifty-four endophytic fungi were isolated from Ricinus communis and screened for their AChE inhibitory activity using Ellman's colorimetric assay method. Six isolates were found to possess AChE inhibitory activity with maximum inhibition of 78 % being evinced by culture Cas1 which was identified to be Alternaria sp. on the basis of molecular as well as microscopic methods. Optimization of inhibitor production was carried out using one factor at a time approach. Maximum production of inhibitor was obtained on potato dextrose broth after 10 days incubation. The IC(50) of the chloroform extract was observed to be 40 μg/ml. The extract was purified on silica gel and eluted stepwise with a gradient of chloroform/methanol. The insecticidal potential of the extract was evaluated by feeding the larvae of Spodoptera litura on diet containing varying concentrations of the extract. It was observed that with increase in the concentration of the extract, mortality of the larvae increased. The culture has the potential of being exploited in medicine as well as a biocontrol agent.

  9. Effects of Chlorophenoxy Herbicides and Their Main Transformation Products on DNA Damage and Acetylcholinesterase Activity

    PubMed Central

    Benfeito, Sofia; Silva, Tiago; Garrido, Jorge; Andrade, Paula B.; Sottomayor, M. J.; Borges, Fernanda; Garrido, E. Manuela

    2014-01-01

    Persistent pesticide transformation products (TPs) are increasingly being detected among different environmental compartments, including groundwater and surface water. However, there is no sufficient experimental data on their toxicological potential to assess the risk associated with TPs, even if their occurrence is known. In this study, the interaction of chlorophenoxy herbicides (MCPA, mecoprop, 2,4-D and dichlorprop) and their main transformation products with calf thymus DNA by UV-visible absorption spectroscopy has been assessed. Additionally, the toxicity of the chlorophenoxy herbicides and TPs was also assessed evaluating the inhibition of acetylcholinesterase activity. On the basis of the results found, it seems that AChE is not the main target of chlorophenoxy herbicides and their TPs. However, the results found showed that the transformation products displayed a higher inhibitory activity when compared with the parent herbicides. The results obtained in the DNA interaction studies showed, in general, a slight effect on the stability of the double helix. However, the data found for 4-chloro-2-methyl-6-nitrophenol suggest that this transformation product can interact with DNA through a noncovalent mode. PMID:24795892

  10. Galangin, a flavonol derived from Rhizoma Alpiniae Officinarum, inhibits acetylcholinesterase activity in vitro.

    PubMed

    Guo, Ava J Y; Xie, Heidi Q; Choi, Roy C Y; Zheng, Ken Y Z; Bi, Cathy W C; Xu, Sherry L; Dong, Tina T X; Tsim, Karl W K

    2010-09-06

    Acetylcholinesterase (AChE) inhibitors are widely used for the treatment of Alzheimer's disease (AD). Several AChE inhibitors, e.g. rivastigmine, galantamine and huperzine are originating from plants, suggesting that herbs could potentially serve as sources for novel AChE inhibitors. Here, we searched potential AChE inhibitors from flavonoids, a group of naturally occurring compounds in plants or traditional Chinese medicines (TCM). Twenty-one flavonoids, covered different subclasses, were tested for their potential function in inhibiting AChE activity from the brain in vitro. Among all the tested flavonoids, galangin, a flavonol isolated from Rhizoma Alpiniae Officinarum, the rhizomes of Alpiniae officinarum (Hance.) showed an inhibitory effect on AChE activity with the highest inhibition by over 55% and an IC(50) of 120 microM and an enzyme-flavonoid inhibition constant (K(i)) of 74 microM. The results suggest that flavonoids could be potential candidates for further development of new drugs against AD.

  11. Maternal caffeine exposure alters neuromotor development and hippocampus acetylcholinesterase activity in rat offspring.

    PubMed

    Souza, Ana Claudia; Souza, Andressa; Medeiros, Liciane Fernandes; De Oliveira, Carla; Scarabelot, Vanessa Leal; Da Silva, Rosane Souza; Bogo, Mauricio Reis; Capiotti, Katiucia Marques; Kist, Luiza Wilges; Bonan, Carla D; Caumo, Wolnei; Torres, Iraci L S

    2015-01-21

    The objective of this study was to evaluate the effects of maternal caffeine intake on the neuromotor development of rat offspring and on acetylcholine degradation and acetylcholinesterase (AChE) expression in the hippocampus of 14-day-old infant rats. Rat dams were treated with caffeine (0.3g/L) throughout gestation and lactation until the pups were 14 days old. The pups were divided into three groups: (1) control, (2) caffeine, and (3) washout caffeine. The washout group received a caffeine solution until the seventh postnatal day (P7). Righting reflex (RR) and negative geotaxis (NG) were assessed to evaluate postural parameters as an index of neuromotor reflexes. An open-field (OF) test was conducted to assess locomotor and exploratory activities as well as anxiety-like behaviors. Caffeine treatment increased both RR and NG latency times. In the OF test, the caffeine group had fewer outer crossings and reduced locomotion compared to control, while the washout group showed increased inner crossings in relation to the other groups and fewer rearings only in comparison to the control group. We found decreased AChE activity in the caffeine group compared to the other groups, with no alteration in AChE transcriptional regulation. Chronic maternal exposure to caffeine promotes important alterations in neuromotor development. These results highlight the ability of maternal caffeine intake to interfere with cholinergic neurotransmission during brain development.

  12. [Effect of acetylcholine and acetylcholinesterase on the activity of contractile vacuole of Amoeba proteus].

    PubMed

    Bagrov, Ia Iu; Manusova, N B

    2011-01-01

    Acetylcholine (ACh, 1 microM) stimulates activity of the contractile vacuole of proteus. The effect of ACh is not mimicked by its analogs which are not hydrolyzed by acetylcholinesterase (AChE), i. e., carbacholine and 5-methylfurmethide. The effect of ACh is not sensitive to the blocking action of M-cholinolytics, atropine and mytolone, but is suppressed by N-cholinolytic, tubocurarine. The inhibitors of AChE, eserine (0.01 microM) and armine (0.1 microM), suppress the effect of ACh on amoeba contractile vacuole. ACh does not affect activation of contractile vacuole induced by arginine-vasopressin (1 microM), but it blocks such effect of opiate receptors agonist, dynorphin A1-13 (0.01 microM). This effect of ACh is also suppressed by the inhibitors of AChE. These results suggest that, in the above-described effects of ACh, AChE acts not as an antagonist, but rather as a synergist.

  13. Sublethal Effects of Insecticide Exposure on Megacopta cribraria (Fabricius) Nymphs: Key Biological Traits and Acetylcholinesterase Activity

    PubMed Central

    Miao, Jin; Reisig, Dominic D.; Li, Guoping; Wu, Yuqing

    2016-01-01

    Megacopta cribraria F. (Hemiptera: Plataspidae), the kudzu bug, is an invasive insect pest of U.S. soybean. At present, insecticide application is the primary and most effective control option for M. cribraria. In this study, the potential effects of sublethal and low-lethal concentrations (LC10 and LC40) of three common insecticides on key biological traits and acetylcholinesterase (AChE) activity of the treated nymphal stage of insect were assessed. The results show that the sublethal concentration of imidacloprid significantly reduced adult emergence rate of M. cribraria. A low-lethal concentration of imidacloprid significantly increased nymphal development time, but significantly decreased adult emergence rate and adult longevity. Both sublethal and low-lethal concentrations of acephate caused an increase in nymphal development time and a reduction in adult emergence rate and adult longevity. Fecundity of females was significantly reduced only by exposure to low-lethal concentrations of acephate. Sublethal and low-lethal concentrations of bifenthrin increased nymphal development time, but significantly decreased adult emergence rate. In addition, we found that the AChE activity of M. cribraria was significantly increased only by LC40 imidacloprid, but strongly inhibited by acephate. PMID:27638957

  14. Variations in Acetylcholinesterase Activity within Human Cortical Pyramidal Neurons Across Age and Cognitive Trajectories.

    PubMed

    Janeczek, Monica; Gefen, Tamar; Samimi, Mehrnoosh; Kim, Garam; Weintraub, Sandra; Bigio, Eileen; Rogalski, Emily; Mesulam, M-Marsel; Geula, Changiz

    2017-03-01

    We described an extensive network of cortical pyramidal neurons in the human brain with abundant acetylcholinesterase (AChE) activity. Emergence of these neurons during childhood/adolescence, attainment of highest density in early adulthood, and virtual absence in other species led us to hypothesize involvement of AChE within these neurons in higher cortical functions. The current study quantified the density and staining intensity of these neurons using histochemical procedures. Few faintly stained AChE-positive cortical pyramidal neurons were observed in children/adolescents. These neurons attained their highest density and staining intensity in young adulthood. Compared with the young adult group, brains of cognitively normal elderly displayed no significant change in numerical density but a significant decrease in staining intensity of AChE-positive cortical pyramidal neurons. Brains of elderly above age 80 with unusually preserved memory performance (SuperAgers) showed significantly lower staining intensity and density of these neurons when compared with same-age peers. Conceivably, low levels of AChE activity could enhance the impact of acetylcholine on pyramidal neurons to counterbalance other involutional factors that mediate the decline of memory capacity during average aging. We cannot yet tell if elderly with superior memory capacity have constitutively low neuronal AChE levels or if this feature reflects adaptive neuroplasticity.

  15. Effects of Anabaena spiroides (Cyanobacteria) aqueous extracts on the acetylcholinesterase activity of aquatic species.

    PubMed

    Monserrat, J M; Yunes, J S; Bianchini, A

    2001-06-01

    The effects of aqueous extracts from a cyanobacteria species, Anabaena spiroides, on fish (Odontesthes argentinensis), crab (Callinectes sapidus), and purified eel acetylcholinesterase (AChE) activity were studied. In vitro concentrations of A. spiroides aqueous extract that inhibited 50% of enzyme activity (IC50) were 23.0, 17.2, and 45.0 mg/L of lyophilized cyanobacteria for eel, fish, and crab AChE, respectively. Eel AChE inhibition follows pseudo-first-order kinetics, the same expected for organophosphorus pesticides. Inhibition of purified eel AChE using mixtures of bioxidized malathion and aqueous extract of A. spiroides showed a competitive feature (p < 0.05), suggesting that the toxin(s) could be structurally similar to an organophosphorus pesticide and that toxins present in the aqueous extract inhibit the active site of the enzyme. The inhibition recovery assays using 2-PAM (0.3 mM) showed that (1) bioxidized malathion inhibited 27.0 +/- 1.1% of crab and 36.5 +/- 0.1% of eel AChE activities; (2) with bioxidized malathion + 2-PAM the registered inhibition was 13.2 +/- 2.1% and 3.7 +/- 0.5% in crab and eel AChE, respectively; (3) the aqueous extract from A. spiroides inhibited 17.4 +/- 2.2% and 59.9 +/- 0.5% of crab and eel AChE activity, respectively; and (4) aqueous extract + 2-PAM inhibited 22.3 +/- 2.6 and 61.5 +/- 0.2% of crab and eel AChEs. The absence of enzyme activity recovery after 2-PAM exposure could imply that the enzyme aging process was extremely quick.

  16. Oxidized low density lipoprotein increases acetylcholinesterase activity correlating with reactive oxygen species production.

    PubMed

    Yamchuen, Panit; Aimjongjun, Sathid; Limpeanchob, Nanteetip

    2014-12-01

    Hyperlipidemia, low density lipoproteins (LDL) and their oxidized forms, and oxidative stress are suspected to be a key combination in the onset of AD and acetylcholinesterase (AChE) plays a part in this pathology. The present study aimed to link these parameters using differentiated SH-SY5Y human neuroblastoma cells in culture. Both mildly and fully oxidized human LDL (mox- and fox-LDL), but not native (non-oxidized) LDL were cytotoxic in dose- and time-dependent patterns and this was accompanied by an increased production of intracellular reactive oxygen species (ROS). Oxidized LDL (10-200 μg/mL) augmented AChE activity after 4 and 24h treatments, respectively while the native LDL was without effect. The increased AChE with oxidized LDLs was accompanied by a proportionate increase in intracellular ROS formation (R=0.904). These findings support the notion that oxidized LDLs are cytotoxic and that their action on AChE may reduce central cholinergic transmission in AD and affirm AChE as a continued rational for anticholinesterase therapy but in conjunction with antioxidant/antihyperlipidemic cotreatments.

  17. Characterization of Lignanamides from Hemp (Cannabis sativa L.) Seed and Their Antioxidant and Acetylcholinesterase Inhibitory Activities.

    PubMed

    Yan, Xiaoli; Tang, Jiajing; dos Santos Passos, Carolina; Nurisso, Alessandra; Simões-Pires, Claudia Avello; Ji, Mei; Lou, Hongxiang; Fan, Peihong

    2015-12-16

    Hemp seed is known for its content of fatty acids, proteins, and fiber, which contribute to its nutritional value. Here we studied the secondary metabolites of hemp seed aiming at identifying bioactive compounds that could contribute to its health benefits. This investigation led to the isolation of 4 new lignanamides, cannabisin M (2), cannabisin N (5), cannabisin O (8), and 3,3'-demethyl-heliotropamide (10), together with 10 known lignanamides, among which 4 was identified for the first time from hemp seed. Structures were established on the basis of NMR, HR-MS, UV, and IR as well as by comparison with the literature data. Lignanamides 2, 7, and 9-14 showed good antioxidant activity, among which 7, 10, and 13 also inhibited acetylcholinesterase in vitro. The newly identified compounds in this study add to the diversity of hemp seed composition, and the bioassays implied that hemp seed, with lignanamides as nutrients, may be a good source of bioactive and protective compounds.

  18. Blocked Enzymatic Etching of Gold Nanorods: Application to Colorimetric Detection of Acetylcholinesterase Activity and Its Inhibitors.

    PubMed

    Saa, Laura; Grinyte, Ruta; Sánchez-Iglesias, Ana; Liz-Marzán, Luis M; Pavlov, Valeri

    2016-05-04

    The anisotropic morphology of gold nanorods (AuNRs) has been shown to lead to nonuniform ligand distribution and preferential etching through their tips. We have recently demonstrated that this effect can be achieved by biocatalytic oxidation with hydrogen peroxide, catalyzed by the enzyme horseradish peroxidase (HRP). We report here that modification of AuNRs with thiol-containing organic molecules such as glutathione and thiocholine hinders enzymatic AuNR etching. Higher concentrations of thiol-containing molecules in the reaction mixture gradually decrease the rate of enzymatic etching, which can be monitored by UV-vis spectroscopy through changes in the AuNR longitudinal plasmon band. This effect can be applied to develop novel optical assays for acetylcholinesterase (AChE) activity. The biocatalytic hydrolysis of acetylthiocholine by AChE yields thiocholine, which prevents enzymatic AuNR etching in the presence of HRP. Additionally, the same bioassay can be used for the detection of nanomolar concentrations of AChE inhibitors such as paraoxon and galanthamine.

  19. Acetylcholinesterase Inhibitory Activity of Pigment Echinochrome A from Sea Urchin Scaphechinus mirabilis

    PubMed Central

    Lee, Sung Ryul; Pronto, Julius Ryan D.; Sarankhuu, Bolor-Erdene; Ko, Kyung Soo; Rhee, Byoung Doo; Kim, Nari; Mishchenko, Natalia P.; Fedoreyev, Sergey A.; Stonik, Valentin A.; Han, Jin

    2014-01-01

    Echinochrome A (EchA) is a dark-red pigment of the polyhydroxynaphthoquinone class isolated from sea urchin Scaphechinus mirabilis. Acetylcholinesterase (AChE) inhibitors are used in the treatment of various neuromuscular disorders, and are considered as strong therapeutic agents for the treatment of Alzheimer’s disease (AD). Although EchA is clinically used to treat ophthalmic diseases and limit infarct formation during ischemia/reperfusion injury, anti-AChE effect of EchA is still unknown. In this study, we investigated the anti-AChE effect of EchA in vitro. EchA and its exhausted form which lost anti-oxidant capacity did not show any significant cytotoxicy on the H9c2 and A7r5 cells. EchA inhibited AChE with an irreversible and uncompetitive mode. In addition, EchA showed reactive oxygen species scavenging activity, particularly with nitric oxide. These findings indicate new therapeutic potential for EchA in treating reduced acetylcholine-related diseases including AD and provide an insight into developing new AChE inhibitors. PMID:24918454

  20. Flavonoids, Antioxidant Potential, and Acetylcholinesterase Inhibition Activity of the Extracts from the Gametophyte and Archegoniophore of Marchantia polymorpha L.

    PubMed

    Wang, Xin; Cao, Jianguo; Wu, Yuhuan; Wang, Quanxi; Xiao, Jianbo

    2016-03-17

    Marchantia polymorpha L. is a representative bryophyte used as a traditional Chinese medicinal herb for scald and pneumonia. The phytochemicals in M. polymorpha L. are terpenoids and flavonoids, among which especially the flavonoids show significant human health benefits. Many researches on the gametophyte of M. polymorpha L. have been reported. However, as the reproductive organ of M. polymorpha L., the bioactivity and flavonoids profile of the archegoniophore have not been reported, so in this work the flavonoid profiles, antioxidant and acetylcholinesterase inhibition activities of the extracts from the archegoniophore and gametophyte of M. polymorpha L. were compared by radical scavenging assay methods (DPPH, ABTS, O(2-)), reducing power assay, acetylcholinesterase inhibition assay and LC-MS analysis. The results showed that the total flavonoids content in the archegoniophore was about 10-time higher than that of the gametophyte. Differences between the archegoniophore and gametophyte of M. polymorpha L. were observed by LC-MS analysis. The archegoniophore extracts showed stronger bio-activities than those of the gametophyte. The archegoniophore extract showed a significant acetylcholinesterase inhibition, while the gametophyte extract hardly inhibited it.

  1. Acetylcholinesterase Activity, Cohabitation with Floricultural Workers, and Blood Pressure in Ecuadorian Children

    PubMed Central

    Jacobs, David R.; Himes, John H.; Alexander, Bruce H.

    2013-01-01

    Background: Acetylcholinesterase (AChE) inhibitors are commonly used pesticides that can effect hemodynamic changes through increased cholinergic stimulation. Children of agricultural workers are likely to have paraoccupational exposures to pesticides, but the potential physiological impact of such exposures is unclear. Objectives: We investigated whether secondary pesticide exposures were associated with blood pressure and heart rate among children living in agricultural Ecuadorian communities. Methods: This cross-sectional study included 271 children 4–9 years of age [51% cohabited with one or more flower plantation workers (mean duration, 5.2 years)]. Erythrocyte AChE activity was measured using the EQM Test-mate system. Linear regression models were used to estimate associations of systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate with AChE activity, living with flower workers, duration of cohabitation with a flower worker, number of flower workers in the child’s home, and number of practices that might increase children’s exposure to pesticides. Results: Mean (± SD) AChE activity was 3.14 ± 0.49 U/mL. A 1-U/mL decrease in AChE activity was associated with a 2.86-mmHg decrease in SBP (95% CI: –5.20, –0.53) and a 2.89-mmHg decrease in DBP (95% CI: –5.00, –0.78), after adjustment for potential confounders. Children living with flower workers had lower SBP (–1.72 mmHg; 95% CI: –3.53, 0.08) than other children, and practices that might increase exposure also were associated with lower SBP. No significant associations were found between exposures and heart rate. Conclusions: Our findings suggest that subclinical secondary exposures to pesticides may affect vascular reactivity in children. Additional research is needed to confirm these findings. PMID:23359481

  2. Copper acutely impairs behavioral function and muscle acetylcholinesterase activity in zebrafish (Danio rerio).

    PubMed

    Haverroth, Gabriela M B; Welang, Chariane; Mocelin, Riciéri N; Postay, Daniela; Bertoncello, Kanandra T; Franscescon, Francini; Rosemberg, Denis B; Dal Magro, Jacir; Dalla Corte, Cristiane L

    2015-12-01

    Copper is a heavy metal found at relatively high concentrations in surface waters around the world. Copper is a micronutrient at low concentrations and is essential to several organisms. At higher concentrations copper can become toxic, which reveal the importance of studying the toxic effects of this metal on the aquatic life. Thus, the objective of this study was to evaluate the toxic effects of copper on the behavior and biochemical parameters of zebrafish (Danio rerio). Zebrafish were exposed for 24h at a concentration of 0.006 mg/L Cu. After the exposure period, behavioral profile of animals was recorded through 6 min using two different apparatuses tests: the Novel Tank and the Light-Dark test. After behavioral testing, animals were euthanized with a solution of 250 mg/L of tricaine (MS-222). Brain, muscle, liver and gills were extracted for analysis of parameters related to oxidative stress and accumulation of copper in these tissues. Acetylcholinesterase (AChE) activity was determined in brain and muscle. Results showed acute exposure to copper induces significant changes in behavioral profile of zebrafish by changing locomotion and natural tendency to avoid brightly lit area. On the other hand, there were no significant effects on parameters related to oxidative stress. AChE activity decreased significantly in zebrafish muscle, but there were no significant changes in cerebral AChE activity. Copper levels in tissues did not increase significantly compared to the controls. Taken together, these results indicate that a low concentration of copper can acutely affect behavioral profile of adult zebrafish which could be partially related to an inhibition on muscle AChE activity. These results reinforce the need of additional tests to establishment of safe copper concentrations to aquatic organisms and the importance of behavioral parameters in ecotoxicological studies.

  3. Chlorpyrifos and Chlorpyrifos-Oxon Inhibit Axonal Growth by Interfering with the Morphogenic Activity of Acetylcholinesterase

    PubMed Central

    Yang, Dongren; Howard, Angela; Bruun, Donald; Ajua-Alemanj, Mispa; Pickart, Cecile; Lein, Pamela J.

    2008-01-01

    A primary role of acetylcholinesterase (AChE) is regulation of cholinergic neurotransmission by hydrolysis of synaptic acetylcholine. In the developing nervous system, however, AChE also functions as a morphogenic factor to promote axonal growth. This raises the question of whether organophosphorus pesticides (OPs) that are known to selectively bind to and inactivate the enzymatic function of AChE also interfere with its morphogenic function to perturb axonogenesis. To test this hypothesis, we exposed primary cultures of sensory neurons derived from embryonic rat dorsal root ganglia (DRG) to chlorpyrifos (CPF) or its oxon metabolite (CPFO). Both OPs significantly decreased axonal length at concentrations that had no effect on cell viability, protein synthesis or the enzymatic activity of AChE. Comparative analyses of the effects of CPF and CPFO on axonal growth in DRG neurons cultured from AChE nullizygous (AChE−/−) versus wildtype (AChE+/+) mice indicated that while these OPs inhibited axonal growth in AChE+/+ DRG neurons, they had no effect on axonal growth in AChE−/− DRG neurons. However, transfection of AChE−/− DRG neurons with cDNA encoding full-length AChE restored the wildtype response to the axon inhibitory effects of OPs. These data indicate that inhibition of axonal growth by OPs requires AChE, but the mechanism involves inhibition of the morphogenic rather than enzymatic activity of AChE. These findings suggest a novel mechanism for explaining not only the functional deficits observed in children and animals following developmental exposure to OPs, but also the increased vulnerability of the developing nervous system to OPs. PMID:18076960

  4. Chlorpyrifos and chlorpyrifos-oxon inhibit axonal growth by interfering with the morphogenic activity of acetylcholinesterase

    SciTech Connect

    Yang Dongren; Howard, Angela; Bruun, Donald; Ajua-Alemanj, Mispa; Pickart, Cecile; Lein, Pamela J.

    2008-04-01

    A primary role of acetylcholinesterase (AChE) is regulation of cholinergic neurotransmission by hydrolysis of synaptic acetylcholine. In the developing nervous system, however, AChE also functions as a morphogenic factor to promote axonal growth. This raises the question of whether organophosphorus pesticides (OPs) that are known to selectively bind to and inactivate the enzymatic function of AChE also interfere with its morphogenic function to perturb axonogenesis. To test this hypothesis, we exposed primary cultures of sensory neurons derived from embryonic rat dorsal root ganglia (DRG) to chlorpyrifos (CPF) or its oxon metabolite (CPFO). Both OPs significantly decreased axonal length at concentrations that had no effect on cell viability, protein synthesis or the enzymatic activity of AChE. Comparative analyses of the effects of CPF and CPFO on axonal growth in DRG neurons cultured from AChE nullizygous (AChE{sup -/-}) versus wild type (AChE{sup +/+}) mice indicated that while these OPs inhibited axonal growth in AChE{sup +/+} DRG neurons, they had no effect on axonal growth in AChE{sup -/-} DRG neurons. However, transfection of AChE{sup -/-} DRG neurons with cDNA encoding full-length AChE restored the wild type response to the axon inhibitory effects of OPs. These data indicate that inhibition of axonal growth by OPs requires AChE, but the mechanism involves inhibition of the morphogenic rather than enzymatic activity of AChE. These findings suggest a novel mechanism for explaining not only the functional deficits observed in children and animals following developmental exposure to OPs, but also the increased vulnerability of the developing nervous system to OPs.

  5. Visible-light-activated photoelectrochemical biosensor for the study of acetylcholinesterase inhibition induced by endogenous neurotoxins.

    PubMed

    Huang, Qilin; Chen, Hua; Xu, Lili; Lu, Danqin; Tang, Linlin; Jin, Litong; Xu, Zhiai; Zhang, Wen

    2013-07-15

    In this report, a novel visible-light-activated photoelectrochemical biosensor was fabricated to study the inhibition of acetylcholinesterase (AChE) activity induced by two endogenous neurotoxins, 1(R)-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline [(R)-Sal] and 1(R),2(N)-dimethyl-6,7-dihydroxy-1,2,3,4-tetra-hydroisoquinoline [(R)-NMSal], which have drawn much attention in the study of the pathogenesis of neurodegenerative diseases such as Parkinson's disease. The photoelectrode was prepared by three steps, as follows. At first, nitrogen and fluorine co-doped TiO2 nanotubes (TNs) were obtained by anodic oxidation of a Ti sheet. Secondly, silver nanoparticles (AgNPs) were deposited onto the TNs through a microwave-assisted heating polyol (MAHP) process. At last, AChE was immobilized on the obtained photoelectrode and the biosensor was marked as AChE/Ag/NFTNs. Due to the nitrogen and fluorine co-doping, the photoelectrochemical biosensors can produce high photocurrent under visible light irradiation. Moreover, the presence of AgNPs greatly increased the photocurrent response of the biosensor. AChE/Ag/NFTNs hybrid system was used to study AChE inhibition induced by (R)-Sal and (R)-NMSal. The result proved that both (R)-Sal and (R)-NMSal exhibited mixed and reversible inhibition against AChE. This strategy is of great significance for the development of novel photoelectrochemical biosensors in the future.

  6. Interpretation of toxicological activity of ionic liquids to acetylcholinesterase inhibition via in silico modelling.

    PubMed

    Cho, Chul-Woong; Yun, Yeoung-Sang

    2016-09-01

    For designing environmentally friendly ionic liquids (ILs), their structural effects on the toxicity should be interpreted via modelling based on the quantitative-structure-activity-relationship (QSAR) concept. For the purpose, QSAR models for predicting IL toxicity in acetylcholinesterase activity were developed by using linear free-energy relationship (LFER) descriptors, whose chemical meanings are well defined. These are excess molar refraction (Ec or a), dipolarity/polarizability (Sc or a), H-bonding acidity (Ac or a), H-bonding basicity (Bc or a), McGowan volume (Vc or a), and ionic interactions of cation (J(+)) and anion (J(-)). Since the experimentally determined LFER descriptors are not available, we calculated them based on density functional theory, conductor-like screening model and the open-source software, obprop. The toxicity values of imidazolium- and pyridinium-based ILs could be predicted by a combination of four descriptors (Ac, Bc, Vc and Sa) with an R(2) of 0.828, and (Ec, Ac, Ea and Sa) with an R(2) of 0.879, respectively. In prediction study using the overall dataset containing various IL structures, the six calculated terms (Ec, Sc, Ac, J(+), Ea, and Sa) were selected and correlated with the observed toxicity values in R(2) of 0.748 for the training set, R(2) of 0.711 for the test set and R(2) of 0.655 for external validation set. And this study explains how the selected terms are contributing to the prediction models, and their chemical meanings were understood.

  7. Neurotoxic effects of nickel chloride in the rainbow trout brain: Assessment of c-Fos activity, antioxidant responses, acetylcholinesterase activity, and histopathological changes.

    PubMed

    Topal, Ahmet; Atamanalp, Muhammed; Oruç, Ertan; Halıcı, Mesut Bünyami; Şişecioğlu, Melda; Erol, Hüseyin Serkan; Gergit, Arzu; Yılmaz, Bahar

    2015-06-01

    The aim of this study was to determine the biochemical, immunohistochemical, and histopathological effects of nickel chloride (Ni) in the rainbow trout brain. Fish were exposed to Ni concentrations (1 mg/L and 2 mg/L) for 21 days. At the end of the experimental period, brain tissues were taken from all fish for c-Fos activity and histopathological examination and determination of acetylcholinesterase (AChE), superoxide dismutase (SOD), catalase (CAT) enzyme activities, lipid peroxidation (LPO), and glutathione (GSH) levels. Our results showed that Ni treatment caused a significant increase in the brain SOD activity and in LPO and GSH levels (p < 0.05), but it significantly decreased AChE and CAT enzyme activities (p < 0.05). Strong induction in c-Fos was observed in some cerebral and cerebellar regions of fish exposed to Ni concentrations when compared with the control group. However, c-Fos activity was decreased in necrotic Purkinje cells. Brain tissues were characterized by demyelination and necrotic changes. These results suggested that Ni treatment causes oxidative stress, changes in c-Fos activity, and histopathological damage in the fish brain.

  8. Distribution of Intravenously Administered Acetylcholinesterase Inhibitor and Acetylcholinesterase Activity in the Adrenal Gland: 11C-Donepezil PET Study in the Normal Rat

    PubMed Central

    Watabe, Tadashi; Naka, Sadahiro; Ikeda, Hayato; Horitsugi, Genki; Kanai, Yasukazu; Isohashi, Kayako; Ishibashi, Mana; Kato, Hiroki; Shimosegawa, Eku; Watabe, Hiroshi; Hatazawa, Jun

    2014-01-01

    Purpose Acetylcholinesterase (AChE) inhibitors have been used for patients with Alzheimer's disease. However, its pharmacokinetics in non-target organs other than the brain has not been clarified yet. The purpose of this study was to evaluate the relationship between the whole-body distribution of intravenously administered 11C-Donepezil (DNP) and the AChE activity in the normal rat, with special focus on the adrenal glands. Methods The distribution of 11C-DNP was investigated by PET/CT in 6 normal male Wistar rats (8 weeks old, body weight  = 220±8.9 g). A 30-min dynamic scan was started simultaneously with an intravenous bolus injection of 11C-DNP (45.0±10.7 MBq). The whole-body distribution of the 11C-DNP PET was evaluated based on the Vt (total distribution volume) by Logan-plot analysis. A fluorometric assay was performed to quantify the AChE activity in homogenized tissue solutions of the major organs. Results The PET analysis using Vt showed that the adrenal glands had the 2nd highest level of 11C-DNP in the body (following the liver) (13.33±1.08 and 19.43±1.29 ml/cm3, respectively), indicating that the distribution of 11C-DNP was the highest in the adrenal glands, except for that in the excretory organs. The AChE activity was the third highest in the adrenal glands (following the small intestine and the stomach) (24.9±1.6, 83.1±3.0, and 38.5±8.1 mU/mg, respectively), indicating high activity of AChE in the adrenal glands. Conclusions We demonstrated the whole-body distribution of 11C-DNP by PET and the AChE activity in the major organs by fluorometric assay in the normal rat. High accumulation of 11C-DNP was observed in the adrenal glands, which suggested the risk of enhanced cholinergic synaptic transmission by the use of AChE inhibitors. PMID:25225806

  9. Unmasking tandem site interaction in human acetylcholinesterase. Substrate activation with a cationic acetanilide substrate.

    PubMed

    Johnson, Joseph L; Cusack, Bernadette; Davies, Matthew P; Fauq, Abdul; Rosenberry, Terrone L

    2003-05-13

    Acetylcholinesterase (AChE) contains a narrow and deep active site gorge with two sites of ligand binding, an acylation site (or A-site) at the base of the gorge, and a peripheral site (or P-site) near the gorge entrance. The P-site contributes to catalytic efficiency by transiently binding substrates on their way to the acylation site, where a short-lived acyl enzyme intermediate is produced. A conformational interaction between the A- and P-sites has recently been found to modulate ligand affinities. We now demonstrate that this interaction is of functional importance by showing that the acetylation rate constant of a substrate bound to the A-site is increased by a factor a when a second molecule of substrate binds to the P-site. This demonstration became feasible through the introduction of a new acetanilide substrate analogue of acetylcholine, 3-(acetamido)-N,N,N-trimethylanilinium (ATMA), for which a = 4. This substrate has a low acetylation rate constant and equilibrates with the catalytic site, allowing a tractable algebraic solution to the rate equation for substrate hydrolysis. ATMA affinities for the A- and P-sites deduced from the kinetic analysis were confirmed by fluorescence titration with thioflavin T as a reporter ligand. Values of a >1 give rise to a hydrolysis profile called substrate activation, and the AChE site-specific mutant W86F, and to a lesser extent wild-type human AChE itself, showed substrate activation with acetylthiocholine as the substrate. Substrate activation was incorporated into a previous catalytic scheme for AChE in which a bound P-site ligand can also block product dissociation from the A-site, and two additional features of the AChE catalytic pathway were revealed. First, the ability of a bound P-site ligand to increase the substrate acetylation rate constant varied with the structure of the ligand: thioflavin T accelerated ATMA acetylation by a factor a(2) of 1.3, while propidium failed to accelerate. Second, catalytic rate

  10. Ortho-7 bound to the active-site gorge of free and OP-conjugated acetylcholinesterase: cation-π interactions.

    PubMed

    Pathak, Arup Kumar; Bandyopadhyay, Tusar

    2016-01-01

    Despite the immense importance of cation-π interactions prevailing in bispyridinium drug acetylcholinesterase (AChE) complexes, a precise description of cation-π interactions at molecular level has remained elusive. Here, we consider a bispyridinium drug, namely, ortho-7 in three different structures of AChE, with and without complexation with organophosphorus (OP) compounds for detailed investigation using all atom molecular dynamics simulation. By quantum mechanical calculations, Y72, W86, Y124, W286, Y337, and Y341 aromatic residues of the enzyme are investigated for possible cation-π interactions with ortho-7. The cation-π interactions in each of the protein-drug complexes are studied using distance, angle, a suitable functional form of them, and electrostatic criteria. The variation of cation-π functional is remarkably consistent with that of the Columbic variation. It is clearly observed that cation-π interactions for some of the residues in the catalytic active site (CAS) and peripheral anionic site (PAS) of the enzyme are either enhanced or reduced based on the nature of OP conjugation (i.e., nerve gas, tabun or pesticide, fenamiphos) when compared with the OP-free enzyme. The strength of cation-π interaction is strongly dependent on the type OP conjugation. The effect of conjugation at CAS is also seen to influence the cation-π interaction at the PAS region. The variation of cation-π interactions on the type of conjugating OP compounds might be suggestive of a reason as to why wide spectrum drug against any OP poisoning is yet to arrive in the market.

  11. Anti-inflammatory, antioxidant and anti-acetylcholinesterase activities of Bouvardia ternifolia: potential implications in Alzheimer's disease.

    PubMed

    García-Morales, Giovanni; Huerta-Reyes, Maira; González-Cortazar, Manasés; Zamilpa, Alejandro; Jiménez-Ferrer, Enrique; Silva-García, Raúl; Román-Ramos, Rubén; Aguilar-Rojas, Arturo

    2015-07-01

    Bouvardia ternifolia has been used medicinally to treat inflammation. In the present study, we investigate the anti-Alzheimer's potential effect of the hydroalcoholic extract of B. ternifolia through evaluation of anti-inflammatory and antioxidant activities, quantification of the percentage inhibition of acetylcholinesterase activity, protection effect against β-amyloid fibrillar-induce neurotoxicity, and the identification of the main constituents. Our results show that B. ternifolia extract and ethyl acetate fraction induced anti-inflammatory effects by reducing inflammation by >70 %, while antioxidant test revealed significant IC50 values for flavonoid content fraction (30.67 ± 2.09 μg/ml) and ethyl acetate fraction (42.66 ± 0.93 μg/ml). The maximum inhibition of acetylcholinesterase was exhibited by scopoletin content fraction (38.43 ± 3.94 %), while ethyl acetate fraction exerted neuroprotective effect against β-amyloid peptide (83.97 ± 5.03 %). Phytochemical analysis, showed the presence of 3-O-quercetin glucopyranoside (415 mg/g), rutin (229.9 mg/g), ursolic and oleanolic acid (54 and 20.8 mg/g respectively), 3-O-quercetin rhamnopyranoside (12.8 mg/g), chlorogenic acid (9.5 mg/g), and scopoletin (1.38 mg/g). Our findings support the use of B. ternifolia since the extract induced significant neuroprotection against β-amyloid peptide, anti-inflammatory, antioxidant and anti-acetylcholinesterase effects that could be attributed to its contents of polyphenols, coumarins, and triterpenes, and encourage further studies for development of this extract as therapeutic agent in treatment of Alzheimer's disease.

  12. Possibility of Acetylcholinesterase Overexpression in Alzheimer Disease Patients after Therapy with Acetylcholinesterase Inhibitors.

    PubMed

    Kračmarová, Alžběta; Drtinová, Lucie; Pohanka, Miroslav

    2015-01-01

    Acetylcholinesterase is an enzyme responsible for termination of excitatory transmission at cholinergic synapses by the hydrolyzing of a neurotransmitter acetylcholine. Nowadays, other functions of acetylcholinesterase in the organism are considered, for example its role in regulation of apoptosis. Cholinergic nervous system as well as acetylcholinesterase activity is closely related to pathogenesis of Alzheimer disease. The mostly used therapy of Alzheimer disease is based on enhancing cholinergic function using inhibitors of acetylcholinesterase like rivastigmine, donepezil or galantamine. These drugs can influence not only the acetylcholinesterase activity but also other processes in treated organism. The paper is aimed mainly on possibility of increased expression and protein level of acetylcholinesterase caused by the therapy with acetylcholinesterase inhibitors.

  13. Guarana (Paullinia cupana) ameliorates memory impairment and modulates acetylcholinesterase activity in Poloxamer-407-induced hyperlipidemia in rat brain.

    PubMed

    Ruchel, Jader B; Braun, Josiane B S; Adefegha, Stephen A; Guedes Manzoni, Alessandra; Abdalla, Fátima H; de Oliveira, Juliana S; Trelles, Kelly; Signor, Cristiane; Lopes, Sônia T A; da Silva, Cássia B; Castilhos, Lívia G; Rubin, Maribel A; Leal, Daniela B R

    2017-01-01

    Hyperlipidemia is a risk factor for the development of cognitive dysfunction and atherosclerosis. Natural compounds have recently received special attention in relation to the treatment of disease due to their low cost and wide margin of safety. Thus, the aim of this study was to determine the possible preventive effect of guarana powder (Paullinia cupana) on memory impairment and acetylcholinesterase (AChE) activity in the brain structures of rats with Poloxamer-407-induced hyperlipidemia. Adult male Wistar rats were pretreated with guarana (12.5, 25 and 50mg/kg/day) and caffeine (0.2mg/kg/day) by gavage for a period of 30days. Simvastatin (0.04mg/kg) was administered as a comparative standard. Acute hyperlipidemia was induced with intraperitoneal injections of 500mg/kg of Poloxamer-407. Memory tests and evaluations of anxiety were performed. The cortex, cerebellum, hippocampus, hypothalamus and striatum were separated to assess acetylcholinesterase activity. Our results revealed that guarana powder was able to reduce the levels of TC and LDL-C in a manner similar to simvastatin. Guarana powder also partially reduced the liver damage caused by hyperlipidemia. Guarana was able to prevent changes in the activity of AChE and improve memory impairment due to hyperlipidemia. Guarana powder may therefore be a source of promising phytochemicals that can be used as adjuvant therapy in the management of hyperlipidemia and cognitive disorders.

  14. Structure-activity relationships and binding mode in the human acetylcholinesterase active site of pseudo-irreversible inhibitors related to xanthostigmine.

    PubMed

    Rizzo, Stefano; Cavalli, Andrea; Ceccarini, Luisa; Bartolini, Manuela; Belluti, Federica; Bisi, Alessandra; Andrisano, Vincenza; Recanatini, Maurizio; Rampa, Angela

    2009-04-01

    Structure-activity relationship studies on acetylcholinesterase (AChE) inhibitors were extended to newly synthesized compounds derived from the lead compound xantostigmine (1). The xanthone ring of compound 1 was replaced with several different scaffolds based on the benzopyran skeleton, linked to the tertiary amino nitrogen through an heptyloxy chain. These modifications resulted in 19 new compounds, most of them showing activity in the nanomolar-subnanomolar range. Docking and molecular dynamics simulations were carried out to both define a new computational protocol for the simulation of pseudo-irreversibile AChE covalent inhibitors, and to acquire a better understanding of the structure-activity relationships of the present series of compounds. The results of this computational work prompted us to to evaluate the ability of compounds 5 and 13 to inhibit acetylcholinesterase-induced Abeta aggregation.

  15. Acetylcholinesterase inhibition, antioxidant activity and toxicity of Peumus boldus water extracts on HeLa and Caco-2 cell lines.

    PubMed

    Falé, P L; Amaral, F; Amorim Madeira, P J; Sousa Silva, M; Florêncio, M H; Frazão, F N; Serralheiro, M L M

    2012-08-01

    This work aimed to study the inhibition on acetylcholinesterase activity (AChE), the antioxidant activity and the toxicity towards Caco-2 and HeLa cells of aqueous extracts of Peumus Boldus. An IC(50) value of 0.93 mg/mL, for AChE inhibition, and EC(50) of 18.7 μg/mL, for the antioxidant activity, was determined. This activity can be attributed to glycosylated flavonoid derivatives detected, which were the main compounds, although boldine and other aporphine derivatives were also present. No changes in the chemical composition or the biochemical activities were found after gastrointestinal digestion. Toxicity of P. boldus decoction gave an IC(50) value 0.66 mg/mL for HeLa cells, which caused significant changes in the cell proteome profile.

  16. Acetylcholinesterase-Inhibition and Antibacterial Activity of Mondia whitei Adventitious Roots and Ex vitro-Grown Somatic Embryogenic-Biomass

    PubMed Central

    Baskaran, Ponnusamy; Kumari, Aloka; Ncube, Bhekumthetho; Van Staden, Johannes

    2016-01-01

    Mondia whitei (Hook.f.) Skeels is an important endangered medicinal and commercial plant in South Africa. In vitro propagation systems are required for biomass production and bioactivity analysis to supplement wild resources/stocks. Adventitious roots from somatic embryogenic explants using suspension culture and ex vitro-grown plants produced via somatic embryogenesis were established using different plant growth regulator treatments. The adventitious root biomass and different parts of ex vitro-grown and mother plants were used to investigate the potential for acetylcholinesterase (AChE) and antibacterial activities. Adventitious roots derived from 2.5 μM indole-3-acetic acid (IAA) treatments and ex vitro-grown plants derived from meta-topolin riboside and IAA treatments gave the best AChE and antibacterial activities. The in vitro-established M. whitei and ex vitro biomass have comparable ability to function as inhibitors of acetylcholinesterase and antibacterial agents, and can be used as potent bioresources in traditional medicine. PMID:27752244

  17. Effects of tricyclic compounds on membrane binding of bivalent cations, activities of acetylcholinesterase and some tissue proteases.

    PubMed

    Molnar, J; Sohar, I; Kovacs, J; Rakonczay, Z; Rausch, H

    1993-01-01

    A tricyclic compound tetrahydroaminoacridine is known to improve the cognitive function in Alzheimer's disease. The possible mechanism of action of acridine and structurally related tricyclic compounds was studied on the bivalent cation content of bacterial membrane, rat brain acetylcholinesterase and some tissue proteases in model experiments. Acridine orange and disubstituted chlorpromazine (CPZ) derivatives lowered Ca2+ and Mg2+ binding and membrane polarization in the simplest biological membrane (E. coli), as revealed by reactor neutron activation analysis. Acetylcholinesterase (AChE) was inhibited by CPZ, 3,7,8-trihydroxy-CPZ, acridine orange partially saturated desipramine, imipramine, trans-clopenthixol and tetrahydrocannabidiolic at 10(-4) to 10(-5). A metalloproteinase, MMP-7-ase, was inhibited by tetrahydrocannabidiolic acid, 3,7,8-trihydroxy-CPZ, acridine orange but other tissue proteinases, ATN-ase and cathepsin B, were less sensitive to these compounds. (ATN-ase is an acetyltyrosine-p-nitroanilide splitting enzyme, a serine protease). The chelate complex forming ability and electron donor capacity of the compounds may play a role in the biological effects tested. It is assumed that compounds which do not displace bivalent cations in membranes may exert an inhibitory effect on AChE, and that metalloproteinase enzymes may be promising for the treatment of degenerative brain diseases.

  18. Behavioral swimming effects and acetylcholinesterase activity changes in Jenynsia multidentata exposed to chlorpyrifos and cypermethrin individually and in mixtures.

    PubMed

    Bonansea, Rocío Inés; Wunderlin, Daniel Alberto; Amé, María Valeria

    2016-07-01

    The pesticides cypermethrin (CYP) and chlorpyrifos (CPF) were found together in water bodies located in agricultural and urban areas. However, the impact to non-target biota from exposure to mixtures has received little attention. In the current study, we evaluated changes in swimming behavior and cholinesterase enzymes activity in Jenynsia multidentata, to investigate the possible effects of these insecticides individually and in mixtures. Moreover, differences between technical and commercial mixtures of the pesticides were evaluated. Females of J. multidentata were exposed over 96-h to CYP (0.04 and 0.4µgL(-1)), CPF (0.4 and 4µgL(-1)), individually and in a technical and commercial mixtures. Swimming behavior was recorded after 24h and 96h of exposure. Also, we measured cholinesterase enzymes activity in brain and muscle after 96h of exposure. Exposure to CYP increased the exploratory activity of J. multidentata in the upper area of the aquarium. Fish exposed to CPF (4µg L(-1)) showed a decrease in swimming activity and an increase in the time spent at the bottom of the aquarium. Interestingly, fish exposed to the technical and commercial mixture of CYP and CPF displayed a different behavior based on the concentration of exposure. Low concentration of pesticides elicited an increase in J. multidentata swimming activity with preference for the upper area of the aquarium, and high concentrations caused decrease in swimming activity with preference for the bottom area of the aquarium. Based on the response of cholinesterase enzymes, acetylcholinesterase in muscle was more sensitive to exposure to CYP, CPF and their mixtures than in brain. A decrease in swimming behavior correlates significantly with the inhibition of acetylcholinesterase activity in muscle of J. multidentata exposed to high concentrations of pesticides. These results draw attention to the need of more studies on the potential ecotoxicological impact of pesticides and its mixtures at

  19. Combined approach to demonstrate acetylcholinesterase activity changes in the rat brain following tabun intoxication and its treatment.

    PubMed

    Bajgar, Jiri; Hajek, Petr; Kassa, Jiri; Slizova, Dasa; Krs, Otakar; Karasova, Jana Zdarova; Fusek, Josef; Capek, Lukas; Voicu, Victor A

    2012-01-01

    Reactivation effects of K203 and currently available oximes (obidoxime, HI-6) in combination with atropine on acetylcholinesterase activities in the brain parts of rats poisoned with tabun were studied. The activity was determined by quantitative histochemical and biochemical methods correlating between them very well. The tabun-induced changes in acetylcholinsterase activity as well as in reactivation potency of reactivators used were different in various parts of the brain. Pontomedullar area seems to be important for observed changes following tabun intoxication and its treatment. From the oximes studied, the reactivation effect of K203 was comparable with obidoxime; HI-6 was ineffective. Combination of bio- and histochemical methods allow fine differentiation among the action of different oximes following tabun poisoning.

  20. Inhibition and Larvicidal Activity of Phenylpropanoids from Piper sarmentosum on Acetylcholinesterase against Mosquito Vectors and Their Binding Mode of Interaction

    PubMed Central

    Hematpoor, Arshia; Liew, Sook Yee; Chong, Wei Lim; Azirun, Mohd Sofian; Lee, Vannajan Sanghiran; Awang, Khalijah

    2016-01-01

    Aedes aegypti, Aedes albopictus and Culex quinquefasciatus are vectors of dengue fever and West Nile virus diseases. This study was conducted to determine the toxicity, mechanism of action and the binding interaction of three active phenylpropanoids from Piper sarmentosum (Piperaceae) toward late 3rd or early 4th larvae of above vectors. A bioassay guided-fractionation on the hexane extract from the roots of Piper sarmentosum led to the isolation and identification of three active phenylpropanoids; asaricin 1, isoasarone 2 and trans-asarone 3. The current study involved evaluation of the toxicity and acetylcholinesterase (AChE) inhibition of these compounds against Aedes aegypti, Aedes albopictus and Culex quinquefasciatus larvae. Asaricin 1 and isoasarone 2 were highly potent against Aedes aegypti, Aedes albopictus and Culex quinquefasciatus larvae causing up to 100% mortality at ≤ 15 μg/mL concentration. The ovicidal activity of asaricin 1, isoasarone 2 and trans-asarone 3 were evaluated through egg hatching. Asaricin 1 and isoasarone 2 showed potent ovicidal activity. Ovicidal activity for both compounds was up to 95% at 25μg/mL. Asaricin 1 and isoasarone 2 showed strong inhibition on acetylcholinesterase with relative IC50 values of 0.73 to 1.87 μg/mL respectively. These findings coupled with the high AChE inhibition may suggest that asaricin 1 and isoasarone 2 are neuron toxic compounds toward Aedes aegypti, Aedes albopictus and Culex quinquefasciatus. Further computational docking with Autodock Vina elaborates the possible interaction of asaricin 1 and isoasarone 2 with three possible binding sites of AChE which includes catalytic triads (CAS: S238, E367, H480), the peripheral sites (PAS: E72, W271) and anionic binding site (W83). The binding affinity of asaricin 1 and isoasarone 2 were relatively strong with asaricin 1 showed a higher binding affinity in the anionic pocket. PMID:27152416

  1. Acetylcholinesterase activity in Corbicula fluminea Mull., as a biomarker of organophosphate pesticide pollution in Pinacanauan River, Philippines.

    PubMed

    Beltran, Kimberly S; Pocsidio, Glorina N

    2010-06-01

    Organophosphates are known to inhibit the enzyme acetylcholinesterase. In this study, the AChE activity from the total soft tissues of Corbicula fluminea Mull. was used as a biomarker of organophosphate pollution in Pinacanauan River. Clams were collected from two different sites and at different seasons of the year. A colorimetric assay on the total soft tissues of the clams showed a directly proportional relationship between enzyme activity and condition of the riverine system. In vitro experiments on the total soft tissue, adductor muscles, digestive glands, and gills were conducted to assess the degree of localization of AChE as well as the sensitivity and tolerance of the enzymes in these tissues to varying concentrations of malathion. The degree of enzyme localization from highest to lowest is as follows: adductor muscle > gills > digestive gland whereas sensitivity to OP from greatest to least is: gills > adductor muscles > digestive gland.

  2. Energetics of Ortho-7 (oxime drug) translocation through the active-site gorge of tabun conjugated acetylcholinesterase.

    PubMed

    Sinha, Vivek; Ganguly, Bishwajit; Bandyopadhyay, Tusar

    2012-01-01

    Oxime drugs translocate through the 20 Å active-site gorge of acetylcholinesterase in order to liberate the enzyme from organophosphorus compounds' (such as tabun) conjugation. Here we report bidirectional steered molecular dynamics simulations of oxime drug (Ortho-7) translocation through the gorge of tabun intoxicated enzyme, in which time dependent external forces accelerate the translocation event. The simulations reveal the participation of drug-enzyme hydrogen bonding, hydrophobic interactions and water bridges between them. Employing nonequilibrium theorems that recovers the free energy from irreversible work done, we reconstruct potential of mean force along the translocation pathway such that the desired quantity represents an unperturbed system. The potential locates the binding sites and barriers for the drug to translocate inside the gorge. Configurational entropic contribution of the protein-drug binding entity and the role of solvent translational mobility in the binding energetics is further assessed.

  3. Synthesis, Characterization, and Evaluation of Difluoropyrido[4,3-b]indoles as Potential Agents for Acetylcholinesterase and Antiamnesic Activity.

    PubMed

    Madaiah, Malavalli; Jayanna, Bidarur K; Manu, Arakere S; Prashanth, Maralekere K; Revanasiddappa, Hosakere D; Veeresh, Bantal

    2017-04-01

    Acetylcholinesterase (AChE) inhibitors are currently the most widely prescribed drugs for Alzheimer's disease. The high potential of indole compounds in medicinal chemistry led us to discover a novel series of fluoroindole compounds. The synthesis and pharmacological analysis of the difluoropyrido[4,3-b]indoles 11-34 are described. Compounds 11-34 were tested for AChE inhibition activity using a rat brain homogenate. Compounds 25-29 display a promising in vitro profile with an IC50 value range of 46-51.6 nM and show significant protective effect on scopolamine-induced amnesia. The present data indicate that compounds 25-29 may represent attractive potent molecules for the treatment of Alzheimer's disease.

  4. [Distribution of acetylcholinesterase activity in the digestive system of the gastropod molluscs Littorina littorea and Achatina fulica].

    PubMed

    Zaĭtseva, O V; Kuznetsova, T V

    2008-01-01

    With the use of the histochemical procedure for the demonstration of acetylcholinesterase (AchE) activity, the distribution cholinergic regulatory elements was studied in the esophagus, the pharynx, the stomach, the liver (the digestive gland) and the intestine in sea and terrestrial gastropod molluscs that differed in their general organization level, lifestyle, habitat and feeding type. In both molluscs, all the parts of the digestive tract contained the significant amount of intraepithelial AchE-positive cells of the open type, single subepithelial neurons and the nervous fibers localized among the muscle cells of the wall of the organs. The basal processes of the AchE-positive intraepithelial cells were shown to form the intraepithelial nerve plexus and to pass under the epithelium. The peculiarities and common principles in the distribution of the nervous elements detected, their possible function and the regulatory role in the digestion in gastropod molluscs and other animals are discussed.

  5. Zebrafish locomotor capacity and brain acetylcholinesterase activity is altered by Aphanizomenon flos-aquae DC-1 aphantoxins.

    PubMed

    Zhang, De Lu; Hu, Chun Xiang; Li, Dun Hai; Liu, Yong Ding

    2013-08-15

    Aphanizomenon flos-aquae (A. flos-aquae) is a source of neurotoxins known as aphantoxins or paralytic shellfish poisons (PSPs) that present a major threat to the environment and to human health. Generally, altered neurological function is reflected in behavior. Although the molecular mechanism of action of PSPs is well known, its neurobehavioral effects on adult zebrafish and its relationship with altered neurological functions are poorly understood. Aphantoxins purified from a natural isolate of A. flos-aquae DC-1 were analyzed by HPLC. The major analogs found in the toxins were the gonyautoxins 1 and 5 (GTX1 and GTX5; 34.04% and 21.28%, respectively) and the neosaxitoxin (neoSTX, 12.77%). Zebrafish (Danio rerio) were intraperitoneally injected with 5.3 and 7.61 μg STXeq/kg (low and high dose, respectively) of A. flos-aquae DC-1 aphantoxins. The swimming activity was investigated by observation combined with video at 6 timepoints from 1 to 24 h post-exposure. Both aphantoxin doses were associated with delayed touch responses, reduced head-tail locomotory abilities, inflexible turning of head, and a tailward-shifted center of gravity. The normal S-pattern (or undulating) locomotor trajectory was replaced by a mechanical motor pattern of swinging the head after wagging the tail. Finally, these fish principally distributed at the top and/or bottom water of the aquarium, and showed a clear polarized distribution pattern at 12 h post-exposure. Further analysis of neurological function demonstrated that both aphantoxin doses inhibited brain acetylcholinesterase activity. All these changes were dose- and time-dependent. These results demonstrate that aphantoxins can alter locomotor capacity, touch responses and distribution patterns by damaging the cholinergic system of zebrafish, and suggest that zebrafish locomotor behavior and acetylcholinesterase can be used as indicators for investigating aphantoxins and blooms in nature.

  6. Acetylcholinesterase immobilization and characterization, and comparison of the activity of the porous silicon-immobilized enzyme with its free counterpart.

    PubMed

    Saleem, Muhammad; Rafiq, Muhammad; Seo, Sung-Yum; Lee, Ki Hwan

    2016-02-02

    A successful prescription is presented for acetylcholinesterase physically adsorbed on to a mesoporous silicon surface, with a promising hydrolytic response towards acetylthiocholine iodide. The catalytic behaviour of the immobilized enzyme was assessed by spectrophotometric bioassay using neostigmine methyl sulfate as a standard acetycholinesterase inhibitor. The surface modification was studied through field emission SEM, Fourier transform IR spectroscopy, energy-dispersive X-ray spectroscopy, cathode luminescence and X-ray photoelectron spectroscopy analysis, photoluminescence measurement and spectrophotometric bioassay. The porous silicon-immobilized enzyme not only yielded greater enzyme stability, but also significantly improved the native photoluminescence at room temperature of the bare porous silicon architecture. The results indicated the promising catalytic behaviour of immobilized enzyme compared with that of its free counterpart, with a greater stability, and that it aided reusability and easy separation from the reaction mixture. The porous silicon-immobilized enzyme was found to retain 50% of its activity, promising thermal stability up to 90°C, reusability for up to three cycles, pH stability over a broad pH of 4-9 and a shelf-life of 44 days, with an optimal hydrolytic response towards acetylthiocholine iodide at variable drug concentrations. On the basis of these findings, it was believed that the porous silicon-immobilized enzyme could be exploited as a reusable biocatalyst and for screening of acetylcholinesterase inhibitors from crude plant extracts and synthesized organic compounds. Moreover, the immobilized enzyme could offer a great deal as a viable biocatalyst in bioprocessing for the chemical and pharmaceutical industries, and bioremediation to enhance productivity and robustness.

  7. Acetylcholinesterase immobilization and characterization, and comparison of the activity of the porous silicon-immobilized enzyme with its free counterpart

    PubMed Central

    Saleem, Muhammad; Rafiq, Muhammad; Seo, Sung-Yum; Lee, Ki Hwan

    2016-01-01

    A successful prescription is presented for acetylcholinesterase physically adsorbed on to a mesoporous silicon surface, with a promising hydrolytic response towards acetylthiocholine iodide. The catalytic behaviour of the immobilized enzyme was assessed by spectrophotometric bioassay using neostigmine methyl sulfate as a standard acetycholinesterase inhibitor. The surface modification was studied through field emission SEM, Fourier transform IR spectroscopy, energy-dispersive X-ray spectroscopy, cathode luminescence and X-ray photoelectron spectroscopy analysis, photoluminescence measurement and spectrophotometric bioassay. The porous silicon-immobilized enzyme not only yielded greater enzyme stability, but also significantly improved the native photoluminescence at room temperature of the bare porous silicon architecture. The results indicated the promising catalytic behaviour of immobilized enzyme compared with that of its free counterpart, with a greater stability, and that it aided reusability and easy separation from the reaction mixture. The porous silicon-immobilized enzyme was found to retain 50% of its activity, promising thermal stability up to 90°C, reusability for up to three cycles, pH stability over a broad pH of 4–9 and a shelf-life of 44 days, with an optimal hydrolytic response towards acetylthiocholine iodide at variable drug concentrations. On the basis of these findings, it was believed that the porous silicon-immobilized enzyme could be exploited as a reusable biocatalyst and for screening of acetylcholinesterase inhibitors from crude plant extracts and synthesized organic compounds. Moreover, the immobilized enzyme could offer a great deal as a viable biocatalyst in bioprocessing for the chemical and pharmaceutical industries, and bioremediation to enhance productivity and robustness. PMID:26839417

  8. Comparative study of oxidative stress parameters and acetylcholinesterase activity in the liver of Pelophylax esculentus complex frogs.

    PubMed

    Prokić, Marko; Borković-Mitić, Slavica; Krizmanić, Imre; Gavrić, Jelena; Despotović, Svetlana; Gavrilović, Branka; Radovanović, Tijana; Pavlović, Slađan; Saičić, Zorica

    2017-01-01

    Comparative activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione reductase (GR), the phase II biotransformation enzyme glutathione-S-transferase (GST), the concentrations of total glutathione (GSH), sulfhydryl groups (-SH) and the activity of the neurotoxicity biomarker acetylcholinesterase (AChE) were investigated in the livers of species belonging to the Pelophylax esculentus "complex" (parental species Pelophylax ridibundus, Pelophylax lessonae, and their hybrid Pelophylax kl. esculentus) from the wetland, Obedska bara in Serbia. The condition factor (CF) and hepato somatic index (HSI) were also calculated. All three species were caught at same locality and were exposed to the same environmental conditions. Liver SOD activity was lower in P. ridibundus than in P. kl. esculentus and P. lessonae; higher activities of CAT, GR and GST were observed in P. kl. esculentus frogs as compared to their parental species. The activity of GSH-Px was significantly lower in P. kl. esculentus. The activity of AChE was increased in P. lessonae as compared to P. kl. esculentus and P. ridibundus. Similar concentrations of GSH and -SH groups were observed in all investigated species. P. kl. esculentus had a higher CF, while the HSI was lower when compared to the parental species. Our findings suggest that the parental species (P. ridibundus and P. lessonae) possess more similar antioxidative responses to environmental conditions than the hybrid species P. kl. esculentus. The obtained results improve our understanding of the biology and physiology of these three closely related species.

  9. Acetylcholinesterase activity in grass shrimp and aqueous pesticide levels from South Florida drainage canals.

    PubMed

    Key, P B; Fulton, M H; Harman-Fetcho, J A; McConnell, L L

    2003-10-01

    Freshwater drainage canals in South Florida are utilized to manage water in agricultural, urban, and water conservation areas and, as a result, collect urban and agricultural storm runoff that is discharged into the Atlantic Ocean and Gulf of Mexico. Pesticides in this runoff may be toxic to the biota inhabiting these waters. This study evaluated the effects of contaminants in South Florida canals draining into Biscayne Bay on the estuarine grass shrimp (Palaemonetes intermedius), a representative invertebrate species. Results of surface water analysis for pesticides indicated that eight pesticides out of 52 analyzed were detected. The herbicide metolachlor was found at all nine sites in the five canals sampled at concentrations up to 119 ng/L. Atrazine was detected at seven sites at concentrations up to 29 ng/L. Three organophosphate insecticides (chlorpyrifos, malathion, diazinon) were detected at three sites in two canals (Military and North). Grass shrimp from these three sites showed significantly reduced levels of the acetylcholinesterase enzyme as compared to control shrimp. These two canals are similar in the land use areas drained--urban and suburban and agriculture. The results suggest that monitoring organisms for AChE levels can be a means of detecting exposure to organophosphorus pesticide contamination.

  10. Aqueous Extracts from Tunisian Diplotaxis: Phenol Content, Antioxidant and Anti-Acetylcholinesterase Activities, and Impact of Exposure to Simulated Gastrointestinal Fluids

    PubMed Central

    Bahloul, Nada; Bellili, Sana; Aazza, Smail; Chérif, Ameur; Faleiro, Maria Leonor; Antunes, Maria Dulce; Miguel, Maria Graça; Mnif, Wissem

    2016-01-01

    Antioxidants have been considered essential for preventing cell damage by scavenging deleterious free radicals. The consumption of antioxidant-rich plants is associated with a reduced risk of some chronic diseases. This study evaluates the antioxidant and acetylcholinesterase inhibition activities of aqueous extracts obtained from different parts of Diplotaxis simplex and Diplotaxis harra from Tunisia. The study also aimed to investigate the action of simulated gastrointestinal juice on antioxidant activities of both extracts. The total phenolic, flavone and flavonol, and flavanone and dihydroflavonol contents were determined by Folin–Ciocalteau, aluminum chloride and 2,4-dinitrophenylhydrazine colorimetric methods, respectively. The metal ion chelating activity, acetylcholinesterase inhibition capacity, and free radical scavenging potential of the extracts towards ABTS (2,2′-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid), DPPH (2,2-diphenyl-1-picrylhydrazyl), hydroxyl, superoxide and nitric oxide were also evaluated. The action of simulated gastro-intestinal fluids on the flavone and flavonol content and total antioxidant activity of the flower extracts was surveyed. Extracts from the seeds and flowers of D. simplex and D. harra displayed the highest amounts of phenols (2691.7 and 2694.5 mg Caffeic Acid Equivalent (CAE)/100 mg; 3433.4 and 2647.2 mg CAE/100 mg, respectively) and flavonols/flavones (2144.4 and 2061.1 mg Rutin Equivalent (RE)/100 g; 1922.6 and 1461.1 mg RE/100 g, respectively). The flower and seed extracts exhibited the highest rates of antioxidant and acetylcholinesterase inhibition activities. A decrease in the flavonoid content and antioxidant activity was observed after extract exposure to simulated saliva. Antioxidant and acetylcholinesterase inhibition activities were noted to depend on plant species and plant parts. In vitro gastrointestinal digestion is useful in assessing the bio-accessibility of compounds with biological activities

  11. Effect of a glyphosate-based herbicide in Cyprinus carpio: assessment of acetylcholinesterase activity, hematological responses and serum biochemical parameters.

    PubMed

    Gholami-Seyedkolaei, Seyed Jalil; Mirvaghefi, Alireza; Farahmand, Hamid; Kosari, Ali Asghar

    2013-12-01

    The objective of this study was to investigate the toxicity effects of acute and sublethal of Roundup® as a glyphosate-based herbicide on acetylcholinesterase (AChE) activity and several hematological and biochemical parameters of Cyprinus carpio. The LC₅₀-96 h of Roundup® to C. carpio was found to be 22.19 ppm. Common carp was subjected to Roundup® at 0 (control), 3.5, 7 and 14 ppm for 16 days, and the AChE activity is verified in tissues of gill, muscle, brain and liver. After 5 days, a significant decrease was observed in the AChE activity of muscle, brain and liver tissues. Besides, a time- and dose-dependent increase in mean cell hemoglobin (MCH) and mean cell volume (MCV) was observed. In contrast, a significant decrease was found in the quantities of hemoglobin (Hb), hematocrit (HCT) and, red (RBC) and white (WBC) blood cell count. Also, the activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) in Roundup® treated groups were significantly higher than the controlled group at experimental periods. However, the level of alkaline phosphatase (ALP) had a significant reduction behavior during the sampling days. It seems that the changes in hematological and biochemical parameters as well as AChE activity could be used as efficient biomarkers in order to determine Roundup® toxicity in aquatic environment.

  12. Exercise effects on activities of Na(+),K(+)-ATPase, acetylcholinesterase and adenine nucleotides hydrolysis in ovariectomized rats.

    PubMed

    Ben, Juliana; Soares, Flávia Mahatma Schneider; Cechetti, Fernanda; Vuaden, Fernanda Cenci; Bonan, Carla Denise; Netto, Carlos Alexandre; Wyse, Angela Terezinha de Souza

    2009-12-11

    Hormone deficiency following ovariectomy causes activation of Na(+),K(+)-ATPase and acetylcholinesterase (AChE) that has been related to cognitive deficits in experimental animals. Considering that physical exercise presents neuroprotector effects, we decide to investigate whether exercise training would affect enzyme activation in hippocampus and cerebral cortex, as well as adenosine nucleotide hydrolysis in synaptosomes from cerebral cortex of ovariectomized rats. Female adult Wistar rats were assigned to one of the following groups: sham (submitted to surgery without removal of the ovaries), exercise, ovariectomized (Ovx) and Ovx plus exercise. Thirty days after surgery, animals were submitted to one month of exercise training, three times per week. After, rats were euthanized, blood serum was collected and hippocampus and cerebral cortex were dissected. Data demonstrated that exercise reversed the activation of Na(+),K(+)-ATPase and AChE activities both in hippocampus and cerebral cortex of ovariectomized rats. Ovariectomy decreased AMP hydrolysis in cerebral cortex and did not alter adenine nucleotides hydrolysis in blood serum. Exercise per se decreased ADP and AMP hydrolysis in cerebral cortex. On the other hand, AMP hydrolysis in blood serum was increased by exercise in ovariectomized adult rats. Present data support that physical exercise might have beneficial effects and constitute a therapeutic alternative to hormone replacement therapy for estrogen deprivation.

  13. Pre-treatment with curcumin modulates acetylcholinesterase activity and proinflammatory cytokines in rats infected with Trypanosoma evansi.

    PubMed

    Wolkmer, Patrícia; Silva, Cássia B da; Paim, Francine C; Duarte, Marta M M F; Castro, Verônica; Palma, Heloisa E; França, Raqueli T; Felin, Diandra V; Siqueira, Lucas C; Lopes, Sonia T A; Schetinger, Maria Rosa C; Monteiro, Silvia G; Mazzanti, Cinthia M

    2013-04-01

    The potent activity against Trypanosomes and health beneficial effects of curcumin (Cur) has been demonstrated in various experimental models. In this study, we evaluated the in vivo effect of Cur as trypanocide and as potential anti-inflammatory agent, through the evaluation of immunomodulatory mechanisms in rats infected with Trypanosoma evansi. Daily oral Cur was administered at doses of 0, 20 or 60mg/kg as preventive treatment (30 and 15days pre infection) and as treatment (post infection). The treatment of the groups continued until the day of euthanasia. Fifteen days after inoculation, parasitemia, plasma proinflammatory cytokines (IFN-γ, TNF-α, IL-1, IL-6), anti-inflammatory cytokines (IL-10) and blood acetylcholinesterase activity (AChE) were analyzed. Pretreatment with Cur reduced parasitemia and lethality. Cur inhibited AChE activity and improved immunological response by cytokines proinflammatory, fundamental during T. evansi infection. We found that Cur is not so important as an antitrypanosomal activity but as immunomodulator agent. These findings reveal that the preventive use of Cur stimulates anti-inflammatory mechanisms, reducing an excessive inflammatory response.

  14. A 1-methyl-4-piperidinyl cytectrene carboxylate labeled by the technetium 99m, a radiotracer for rat brain acetylcholinesterase activity.

    PubMed

    Mejri, Najoua; Barhoumi, Chokri; Trabelsi, Moez; Mekni, Abdelkader; Said, Nadia Malek; Saidi, Mouldi

    2010-02-01

    Alzheimer's disease (AD) is a degenerative neurological disorder that causes progressive and irreversible loss of connections between brain cells and loss of mental functions. Clinical and postmortem studies show that the biochemical changes in brains of AD patients include decrease in acetylcholinesterase (AChE) activity. Our aim was to study AChE activity using piperidinyl ester labelled with technetium-99m. In vivo and in vitro studies demonstrated that labelled piperidinyl ester was a substrate for AChE. The hydrolytic rate of this substrate was measured and the specificity was evaluated using the inhibitor BW284c51. The rhenium analogues of the technetium-labelled substrate were used to determine the affinity constant (K(m)) and the maximum reaction velocity (V(max)) because of the high specific activity of technetium. The high hydrolytic rate and high specificity of the substrate for AChE make it suitable as an in vivo radiotracer for studying AChE activity in the brain.

  15. Shift in aggregation, ROS generation, antioxidative defense, lysozyme and acetylcholinesterase activities in the cells of an Indian freshwater sponge exposed to washing soda (sodium carbonate).

    PubMed

    Mukherjee, Soumalya; Ray, Mitali; Ray, Sajal

    2016-09-01

    Washing soda, chemically identified as anhydrous sodium carbonate, is a popular cleaning agent among the rural and urban populations of India which often contaminates the freshwater ponds and lakes, the natural habitat of sponge Eunapius carteri. Present investigation deals with estimation of cellular aggregation, generation of ROS and activities of antioxidant enzymes, lysozyme and acetylcholinesterase in the cells of E. carteri under the environmentally realistic concentrations of washing soda. Prolonged treatment of washing soda inhibited the degree of cellular aggregation. Experimental exposure of 8 and 16mg/l of sodium carbonate for 48h elevated the physiological level of reactive oxygen species (ROS) generation in the agranulocytes, semigranulocytes and granulocytes of E. carteri, whereas, treatment of 192h inhibited the ROS generation in three cellular morphotypes. Activities of superoxide dismutase, catalase and glutathione-S-transferase were recorded to be inhibited under prolonged exposure of washing soda. Washing soda mediated inhibition of ROS generation and depletion in the activities of antioxidant enzymes were indicative to an undesirable shift in cytotoxic status and antioxidative defense in E. carteri. Inhibition in the activity of lysozyme under the treatment of sodium carbonate was suggestive to a severe impairment of the innate immunological efficiency of E. carteri distributed in the washing soda contaminated habitat. Washing soda mediated inhibition in the activity of acetylcholinesterase indicated its neurotoxicity in E. carteri. Washing soda, a reported environmental contaminant, affected adversely the immunophysiological status of E. carteri with reference to cellular aggregation, oxidative stress, antioxidative defense, lysozyme and acetylcholinesterase activity.

  16. Assessment of acetylcholinesterase and butyrylcholinesterase activities in blood plasma of agriculture workers

    PubMed Central

    Dhananjayan, V.; Ravichandran, B.; Anitha, N.; Rajmohan, H. R.

    2012-01-01

    Background: Cholinesterase determination indicates whether the person has been under pesticide exposure is not. It is recommended that the worker′s cholinesterase level should be assessed for workers at a pesticide applied region. Hence, cholinesterase activities in blood samples of agricultural workers exposed to vegetables and grape cultivation with age matched, unexposed workers, who never had any exposure to pesticides, were estimated. Methods: The detailed occupational history and lifestyle characters were obtained by questionnaire. Cholinesterase activity was determined by the method of Ellman as modified by Chambers and Chambers. Results: AChE was ranging from 1.65 to 3.54μmoles/min/ml in exposed subjects where as it was ranged from 2.22 to 3.51μmoles/min/ml in control subjects. BChE activity was ranging from 0.16 to 5.2μmoles/min/ml among exposed subjects, where as it was ranged from 2.19 to 5.06μmoles/min/ml in control subjects. The results showed statistically significant reduction in enzyme activities (AChE 14%; BChE 56%) among exposed subjects. Conclusion: It was concluded that the reduction in cholinesterase activity may lead to varieties of effects. Hence it is compulsory to use protective gadgets during pesticide spray. Further a continuous biomonitoring study is recommended to assess pesticide exposure. PMID:23776322

  17. A fluorometric assay for acetylcholinesterase activity and inhibitor detection based on DNA-templated copper/silver nanoclusters.

    PubMed

    Li, Wenhua; Li, Wang; Hu, Yufang; Xia, Yalin; Shen, Qinpeng; Nie, Zhou; Huang, Yan; Yao, Shouzhuo

    2013-09-15

    A novel label-free, rapid, cost-effective, and highly sensitive fluorometric sensor has been constructed for the detection of acetylcholinesterase (AChE) activity and its inhibitor based on the fluorescence quenching of DNA-templated copper/silver nanoclusters (DNA-Cu/AgNCs). In this assay, AChE catalyzes the hydrolysis of acetylthiocholine (ATCh) to form thiocholine which induces fluorescence quenching of DNA-Cu/AgNCs. The AChE activity could be detected as low as 0.05mU/mL and with a linear range from 0.05 to 2.0mU/mL. This assay offers a very convenient "mix and detect" approach for AChE activity. On the other hand, tacrine and organophosphorus pesticides (OPPs) were employed to inhibit the hydrolysis of ATCh, which could eliminate the fluorescence quenching of DNA-Cu/AgNCs. The IC50 of tacrine and methamidophos were estimated to be 16.9nM and 0.075mg/L, respectively. This method was also used to detect spiked OPPs in agricultural products successfully. The present work may expand the use of DNA-Cu/AgNCs to the field of enzyme sensors.

  18. Rosmarinus officinalis L. leaf extract improves memory impairment and affects acetylcholinesterase and butyrylcholinesterase activities in rat brain.

    PubMed

    Ozarowski, Marcin; Mikolajczak, Przemyslaw L; Bogacz, Anna; Gryszczynska, Agnieszka; Kujawska, Malgorzata; Jodynis-Liebert, Jadwiga; Piasecka, Anna; Napieczynska, Hanna; Szulc, Michał; Kujawski, Radoslaw; Bartkowiak-Wieczorek, Joanna; Cichocka, Joanna; Bobkiewicz-Kozlowska, Teresa; Czerny, Boguslaw; Mrozikiewicz, Przemyslaw M

    2013-12-01

    Rosmarinus officinalis L. leaf as part of a diet and medication can be a valuable proposal for the prevention and treatment of dementia. The aim of the study was to assess the effects of subchronic (28-fold) administration of a plant extract (RE) (200 mg/kg, p.o.) on behavioral and cognitive responses of rats linked with acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activity and their mRNA expression level in the hippocampus and frontal cortex. The passive avoidance test results showed that RE improved long-term memory in scopolamine-induced rats. The extract inhibited the AChE activity and showed a stimulatory effect on BuChE in both parts of rat brain. Moreover, RE produced a lower mRNA BuChE expression in the cortex and simultaneously an increase in the hippocampus. The study suggests that RE led to improved long-term memory in rats, which can be partially explained by its inhibition of AChE activity in rat brain.

  19. Alkaloid metabolite profiles by GC/MS and acetylcholinesterase inhibitory activities with binding-mode predictions of five Amaryllidaceae plants.

    PubMed

    Cortes, Natalie; Alvarez, Rafael; Osorio, Edison H; Alzate, Fernando; Berkov, Strahil; Osorio, Edison

    2015-01-01

    Acetylcholinesterase (AChE) enzymatic inhibition is an important target for the management of Alzheimer disease (AD) and AChE inhibitors are the mainstay drugs for its treatment. In order to discover new sources of potent AChE inhibitors, a combined strategy is presented based on AChE-inhibitory activity and chemical profiles by GC/MS, together with in silico studies. The combined strategy was applied on alkaloid extracts of five Amaryllidaceae species that grow in Colombia. Fifty-seven alkaloids were detected using GC/MS, and 21 of them were identified by comparing their mass-spectral fragmentation patterns with standard reference spectra in commercial and private library databases. The alkaloid extracts of Zephyranthes carinata exhibited a high level of inhibitory activity (IC50 = 5.97 ± 0.24 μg/mL). Molecular modeling, which was performed using the structures of some of the alkaloids present in this extract and the three-dimensional crystal structures of AChE derived from Torpedo californica, disclosed their binding configuration in the active site of this AChE. The results suggested that the alkaloids 3-epimacronine and lycoramine might be of interest for AChE inhibition. Although the galanthamine group is known for its potential utility in treating AD, the tazettine-type alkaloids should be evaluated to find more selective compounds of potential benefit for AD.

  20. Larvicidal and acetylcholinesterase inhibitory activities of apiaceae plant essential oils and their constituents against aedes albopictus and formulation development.

    PubMed

    Seo, Seon-Mi; Jung, Chan-Sik; Kang, Jaesoon; Lee, Hyo-Rim; Kim, Sung-Woong; Hyun, Jinho; Park, Il-Kwon

    2015-11-18

    This study evaluated the larvicidal activity of 12 Apiaceae plant essential oils and their components against the Asian tiger mosquito, Aedes albopictus, and the inhibition of acetylcholine esterase with their components. Of the 12 plant essential oils tested, ajowan (Trachyspermum ammi), caraway seed (Carum carvi), carrot seed (Daucus carota), celery (Apium graveolens), cumin (Cuminum cyminum), dill (Anethum graveolens), and parsley (Petroselinum sativum) resulted in >90% larval mortality when used at 0.1 mg/mL. Of the compounds identified, α-phellandrene, α-terpinene, p-cymene, (-)-limonene, (+)-limonene, γ-terpinene, cuminaldehyde, neral, (S)-+-carvone, trans-anethole, thymol, carvacrol, myristicin, apiol, and carotol resulted in >80% larval mortality when used at 0.1 mg/mL. Two days after treatment, 24.69, 3.64, and 12.43% of the original amounts of the celery, cumin, and parsley oils, respectively, remained in the water. Less than 50% of the original amounts of α-phellandrene, 1,8-cineole, terpinen-4-ol, cuminaldehyde, and trans-antheole were detected in the water at 2 days after treatment. Carvacrol, α-pinene, and β-pinene inhibited the activity of Ae. albopictus acetylcholinesterase with IC50 values of 0.057, 0.062, and 0.190 mg/mL, respectively. A spherical microemulsion of parsley essential oil-loaded poly(vinyl alcohol) (PVA) was prepared, and the larvicidal activity of this formulation was shown to be similar to that of parsley oil.

  1. Selective and sensitive detection of acetylcholinesterase activity using denatured protein-protected gold nanoclusters as a label-free probe.

    PubMed

    Li, Hongchang; Guo, Yuxin; Xiao, Lehui; Chen, Bo

    2014-01-07

    Based on the fluorescence quenching of novel denatured protein-protected gold nanoclusters, a label-free detection method of acetylcholinesterase (AChE) activity has been developed. Using denatured bovine serum albumin (dBSA), in which 35 cysteine residues can interact polyvalently with Au nanoclusters (AuNCs) as a stabilizing agent, water-soluble and stable fluorescent gold nanoclusters were synthesized. The fluorescence of the AuNCs was quenched by thiocholine that was produced from the AChE hydrolysis of S-acetylthiocholine iodide (ACTI) to detect the AChE activity. The linear range of the method was 0.005-0.15 U mL(-1). The limit of detection (LOD) was 0.02 mU mL(-1). Other enzymes and metal ions, i.e., GPT, γ-GT, GOx, K(+), Ca(2+) and Na(+), showed minimal interference. Using the fluorescence probe, satisfactory results for the detection of the AChE activity in human serum were obtained.

  2. Postnatal growth hormone deficiency in growing rats causes marked decline in the activity of spinal cord acetylcholinesterase but not butyrylcholinesterase.

    PubMed

    Koohestani, Faezeh; Brown, Chester M; Meisami, Esmail

    2012-11-01

    The effects of growth hormone (GH) deficiency on the developmental changes in the abundance and activity of cholinesterase enzymes were studied in the developing spinal cord (SC) of postnatal rats by measuring the specific activity of acetylcholinesterase (AChE), a marker for cholinergic neurons and their synaptic compartments, and butyrylcholinesterase (BuChE), a marker for glial cells and neurovascular cells. Specific activities of these two enzymes were measured in SC tissue of 21- and 90 day-old (P21, weaning age; P90, young adulthood) GH deficient spontaneous dwarf (SpDwf) mutant rats which lack anterior pituitary and circulating plasma GH, and were compared with SC tissue of normal age-matched control animals. Assays were carried out for AChE and BuChE activity in the presence of their specific chemical inhibitors, BW284C51 and iso-OMPA, respectively. Results revealed that mean AChE activity was markedly and significantly reduced [28% at P21, 49% at P90, (p<0.01)] in the SC of GH deficient rats compared to age-matched controls. GH deficiency had a higher and more significant effect on AChE activity of the older (P90) rats than the younger ones (P21) ones. In contrast, BuChE activity in SC showed no significant changes in GH deficient rats at either of the two ages studied. Results imply that, in the absence of pituitary GH, the postnatal proliferation of cholinergic synapses in the rat SC, a CNS structure, where AChE activity is abundant, is markedly reduced during both the pre- and postweaning periods; more so in the postweaning than preweaning ages. In contrast, the absence of any effects on BuChE activity implies that GH does not affect the development of non-neuronal elements, e.g., glia, as much as the neuronal and synaptic compartments of the developing rat SC.

  3. Hypothyroidism Enhanced Ectonucleotidases and Acetylcholinesterase Activities in Rat Synaptosomes can be Prevented by the Naturally Occurring Polyphenol Quercetin.

    PubMed

    Baldissarelli, Jucimara; Santi, Adriana; Schmatz, Roberta; Abdalla, Fátima Husein; Cardoso, Andréia Machado; Martins, Caroline Curry; Dias, Glaecir R Mundstock; Calgaroto, Nicéia Spanholi; Pelinson, Luana Paula; Reichert, Karine Paula; Loro, Vania Lucia; Morsch, Vera Maria Melchiors; Schetinger, Maria Rosa Chitolina

    2017-01-01

    Thyroid hormones have an influence on the functioning of the central nervous system. Furthermore, the cholinergic and purinergic systems also are extensively involved in brain function. In this context, quercetin is a polyphenol with antioxidant and neuroprotective properties. This study investigated the effects of (MMI)-induced hypothyroidism on the NTPDase, 5'-nucleotidase, adenosine deaminase (ADA), and acetylcholinesterase (AChE) activities in synaptosomes of rats and whether the quercetin can prevent it. MMI at a concentration of 20 mg/100 mL was administered for 90 days in the drinking water. The animals were divided into six groups: control/water (CT/W), control/quercetin 10 mg/kg, control/quercetin 25 mg/kg, methimazole/water (MMI/W), methimazole/quercetin 10 mg/kg (MMI/Q10), and methimazole/quercetin 25 mg/kg (MMI/Q25). On the 30th day, hormonal dosing was performed to confirm hypothyroidism, and the animals were subsequently treated with 10 or 25 mg/kg quercetin for 60 days. NTPDase activity was not altered in the MMI/W group. However, treatment with quercetin decreased ATP and ADP hydrolysis in the MMI/Q10 and MMI/Q25 groups. 5'-nucleotidase activity increased in the MMI/W group, but treatments with 10 or 25 mg/kg quercetin decreased 5'-nucleotidase activity. ADA activity decreased in the CT/25 and MMI/Q25 groups. Furthermore, AChE activity was reduced in all groups with hypothyroidism. In vitro tests also demonstrated that quercetin per se decreased NTPDase, 5'-nucleotidase, and AChE activities. This study demonstrated changes in the 5'-nucleotidase and AChE activities indicating that purinergic and cholinergic neurotransmission are altered in this condition. In addition, quercetin can alter these parameters and may be a promising natural compound with important neuroprotective actions in hypothyroidism.

  4. [Effect of improving memory and inhibiting acetylcholinesterase activity by invigorating-qi and warming-yang recipe].

    PubMed

    Liu, Z Y; Yang, Y G; Zheng, B

    1993-11-01

    Invigorating-Qi and Warming-Yang (IQWY) had a good curative effect to some senile diseases such as senile dementia, senile hypomnesia etc. This experiment was designed for probing into the therapeutical mechanism of IQWY recipe. BALB/C pure bred mice were divided into five groups. Group I was taken per os of invigorating Qi (IQ), Group II warming Yang (WY), Group III IQWY drugs, Group IV was dysmnesia model, and Group V blank control group injected with normal saline only. All groups except Group V were injected scopolamine (5mg/kg) intraperitoneally to induce dysmnesia model after medication. IQ drug consisted of Codonopsis pilosula, Astragalus membranaceus, Poria cocos, and Glycyrrhiza uralensis, WY drug of Cynomorium songoricum, Epimedium brevicornum and Cuscuta chinensis, while IQWY recipe consisted of both IQ and WY drugs. The results showed that IQ, WY and IQWY had an evident antagonistic action to Scopolamine induced dysmnesia mice, and could improve their memory. The erroneous times of the animal's reaction in Group I, II and III were less than those in Group IV, P < 0.05 or P < 0.01. Acetylcholinesterase (AchE) activity in the mice could be inhibited by IQ, WY and IQWY also. The activity in Group I, II and III was less than that in Group IV and V, P < 0.05 or P < 0.01. The therapeutic mechanism of IQWY was in connection with its effect to M-cholinergic transmitters of central nervous system.

  5. Effects of chlorpyrifos ethyl on acetylcholinesterase activity in climbing perch cultured in rice fields in the Mekong Delta, Vietnam.

    PubMed

    Nguyen, Tam Thanh; Berg, Håkan; Nguyen, Hang Thi Thuy; Nguyen, Cong Van

    2015-07-01

    Climbing perch is commonly harvested in rice fields and associated wetlands in the Mekong Delta. Despite its importance in providing food and income to local households, there is little information how this fish species is affected by the high use of pesticides in rice farming. Organophosphate insecticides, such as chlorpyrifos ethyl, which are highly toxic to aquatic organisms, are commonly used in the Mekong Delta. This study shows that the brain acetylcholinesterase (AChE) activity in climbing perch fingerlings cultured in rice fields, was significantly inhibited by a single application of chlorpyrifos ethyl, at doses commonly applied by rice farmers (0.32-0.64 kg/ha). The water concentration of chlorpyrifos ethyl decreased below the detection level within 3 days, but the inhibition of brain AChE activity remained for more than 12 days. In addition, the chlorpyrifos ethyl treatments had a significant impact on the survival and growth rates of climbing perch fingerlings, which were proportional to the exposure levels. The results indicate that the high use of pesticides among rice farmers in the Mekong Delta could have a negative impact on aquatic organisms and fish yields, with implications for the aquatic biodiversity, local people's livelihoods and the aquaculture industry in the Mekong Delta.

  6. A selective molecularly imprinted polymer for immobilization of acetylcholinesterase (AChE): an active enzyme targeted and efficient method.

    PubMed

    Demirci, Gökhan; Doğaç, Yasemin İspirli; Teke, Mustafa

    2015-11-01

    In the present study, we immobilized acetylcholinesterase (AChE) enzyme onto acetylcholine removed imprinted polymer and acetylcholine containing polymer. First, the polymers were produced with acetylcholine, substrate of AChE, by dispersion polymerization. Then, the enzyme was immobilized onto the polymers by using two different methods: In the first method (method A), acetylcholine was removed from the polymer, and then AChE was immobilized onto this polymer (acetylcholine removed imprinted polymer). In the second method (method B), AChE was immobilized onto acetylcholine containing polymer by affinity. In method A, enzyme-specific species (binding sites) occurred by removing acetylcholine from the polymer. The immobilized AChE reached 240% relative specific activity comparison with free AChE because the active enzyme molecules bounded onto the polymer. Transmission electron microscopy results were taken before and after immobilization of AChE for the assessment of morphological structure of polymer. Also, the experiments, which include optimum temperature (25-65 °C), optimum pH (3-10), thermal stability (4-70 °C), kinetic parameters, operational stability and reusability, were performed to determine the characteristic of the immobilized AChE.

  7. Ultrahigh pressure-assisted enzymatic extraction maximizes the yield of longan pulp polysaccharides and their acetylcholinesterase inhibitory activity in vitro.

    PubMed

    Bai, Yajuan; Liu, Lei; Zhang, Ruifen; Huang, Fei; Deng, Yuanyuan; Zhang, Mingwei

    2017-03-01

    An extraction method employing ultrahigh pressure-assisted enzymatic treatment was developed and optimized by response surface methodology to increase the yield of longan pulp polysaccharides (LP-UE). A maximum polysaccharides yield of 8.55% was obtained under the optimal conditions of 407MPa ultrahigh pressure maintained for 6min with an enzyme to pretreated material ratio of 1:100, an enzymolysis time of 1.7h and a water to pretreated material ratio of 42ml/g. Subsequently, the physicochemical properties and acetylcholinesterase (AChE) inhibitory activity of LP-UE were compared to those of longan pulp polysaccharides (LP) extracted by hot water (LP-H), ultrahigh pressure (LP-U) or enzymatic treatment (LP-E). Results demonstrated that the extraction yield, hexuronic acid content and AChE inhibitory activity of LP-UE was the highest among the four LP samples. LP-UE was primarily made up of arabinose, glucose, and galactose and was linked mainly by β-type glycosidic linkage. The FTIR spectrum of LP-UE was very similar to those of LP-H, LP-U, and LP-E. In summary, ultrahigh pressure-assisted enzymatic treatment is a more efficient technique for extracting LP with considerable improvement of both yield and memory enhancement function.

  8. Characterization of acetylcholinesterase from elm left beetle, Xanthogaleruca luteola and QSAR of temephos derivatives against its activity.

    PubMed

    Sharifi, Mahboobeh; Ghadamyari, Mohammad; Gholivand, Khodayar; Valmoozi, Ali Asghar Ebrahimi; Sajedi, Reza H

    2017-03-01

    Insect acetylcholinesterase (AChE) is the principal target for organophosphate (OP) and carbamate (CB) insecticides. In this research, an AChE from third instar larvae of elm left beetle, Xanthogaleruca luteola was purified by affinity chromatography. The enzyme was purified 75.29-fold with a total yield of 8.51%. As shown on denaturing SDS-PAGE, the molecular mass of purified AChE was 70kDa. The enzyme demonstrated maximum activity at pH7 and 35°C. Furthermore, a series of temephos (Tem) derivatives with the general structure of P(O)XP(O) (1-44) were prepared, synthesized and characterized by (31)P, (13)C, (1)H NMR and FT-IR spectral techniques. The toxicity of 36 new Tem derivatives was screened on the third instar larvae and the compound compound 1,2 cyclohexane-N,N'-bis(N,N'-piperidine phosphoramidate) exhibited the highest insecticidal potential. The method of kinetic analysis is applied in order to obtain the maximum velocity (Vmax), the Michaelis constant (Km) and the parameters characterizing the inhibition type for inhibitors with >75% mortality in preliminary bioassay. The inhibition mechanism was mixed and inhibitory constant (Ki) was calculated as 4.70μM(-1)min(-1) for this compound. Quantitative structure-activity relationship (QSAR) equations of these compounds indicated that the electron orbital energy has major effect on insecticidal properties.

  9. Intracerebroventricular D-galactose administration impairs memory and alters activity and expression of acetylcholinesterase in the rat.

    PubMed

    Rodrigues, André Felipe; Biasibetti, Helena; Zanotto, Bruna Stela; Sanches, Eduardo Farias; Pierozan, Paula; Schmitz, Felipe; Parisi, Mariana Migliorini; Barbé-Tuana, Florencia; Netto, Carlos Alexandre; Wyse, Angela T S

    2016-05-01

    Tissue accumulation of galactose is a hallmark in classical galactosemia. Cognitive deficit is a symptom of this disease which is poorly understood. The aim of this study was to investigate the effects of intracerebroventricular administration of galactose on memory (inhibitory avoidance and novel object recognition tasks) of adult rats. We also investigated the effects of galactose on acetylcholinesterase (AChE) activity, immunocontent and gene expression in hippocampus and cerebral cortex. Wistar rats received a single injection of galactose (4mM) or saline (control). For behavioral parameters, galactose was injected 1h or 24h previously to the testing. For biochemical assessment, animals were decapitated 1h, 3h or 24h after galactose or saline injection; hippocampus and cerebral cortex were dissected. Results showed that galactose impairs the memory formation process in aversive memory (inhibitory avoidance task) and recognition memory (novel object recognition task) in rats. The activity of AChE was increased, whereas the gene expression of this enzyme was decreased in hippocampus, but not in cerebral cortex. These findings suggest that these changes in AChE may, at least in part, to lead to memory impairment caused by galactose. Taken together, our results can help understand the etiopathology of classical galactosemia.

  10. The Nature of Activated Non-classical Hydrogen Bonds: A Case Study on Acetylcholinesterase-Ligand Complexes.

    PubMed

    Berg, Lotta; Mishra, Brijesh Kumar; Andersson, C David; Ekström, Fredrik; Linusson, Anna

    2016-02-18

    Molecular recognition events in biological systems are driven by non-covalent interactions between interacting species. Here, we have studied hydrogen bonds of the CH⋅⋅⋅Y type involving electron-deficient CH donors using dispersion-corrected density functional theory (DFT) calculations applied to acetylcholinesterase-ligand complexes. The strengths of CH⋅⋅⋅Y interactions activated by a proximal cation were considerably strong; comparable to or greater than those of classical hydrogen bonds. Significant differences in the energetic components compared to classical hydrogen bonds and non-activated CH⋅⋅⋅Y interactions were observed. Comparison between DFT and molecular mechanics calculations showed that common force fields could not reproduce the interaction energy values of the studied hydrogen bonds. The presented results highlight the importance of considering CH⋅⋅⋅Y interactions when analysing protein-ligand complexes, call for a review of current force fields, and opens up possibilities for the development of improved design tools for drug discovery.

  11. Effect of high fat diets on the NTPDase, 5'-nucleotidase and acetylcholinesterase activities in the central nervous system.

    PubMed

    Kaizer, Rosilene Rodrigues; Spanevello, Rosélia Maria; Costa, Eduarda; Morsch, Vera Maria; Schetinger, Maria Rosa Chitolina

    2017-03-01

    High fat diets are associated with the promotion of neurological diseases, such as Alzheimer disease (AD). This study aim investigate the high fat diets role to promotion of AD using as biochemistry parameter of status of central nervous system through the NTPDase, 5'-nucleotidase and acetylcholinesterase (AChE) activities in brain of young rats. The intake of high fat diets promotes an inhibition of purinergic and cholinergic functions, mainly in the long-term exposure to saturated and saturated/unsaturated diets. The AChE activity was decreased to supernatant and synaptosomes tissues preparations obtained from cerebral cortex in average of 20%, to both groups exposed to saturated and saturated/unsaturated diets, when compared to the control group. Very similar results were found in hippocampus and cerebellum brain areas. At same time, the adenine nucleotides hydrolysis in synaptosomes of cerebral cortex were decreased to ATP, ADP and AMP after the long-term exposure to high fat diets, as saturated and saturated/unsaturated. The inhibition of ATP hydrolysis was of 26% and 39% to saturated and saturated/unsaturated diets, respectively. ADP hydrolysis was decreased in 20% to saturated diet, and AMP hydrolysis was decreased in 25% and 33% to saturated and saturated/unsaturated diets, respectively, all in comparison to the control. Thus, we can suggest that the effects of high diets on the purinergic and cholinergic nervous system may contribute to accelerate the progressive memory loss, to decline in language and other cognitive disruptions, such as AD patients presents.

  12. Local salt substitutes “Obu-otoyo” activate acetylcholinesterase and butyrylcholinesterase and induce lipid peroxidation in rat brain

    PubMed Central

    Oboh, Ganiyu; Ademiluyi, Adedayo O.

    2015-01-01

    Evidence has shown that ingestion of heavy metals can lead to neurodegenerative diseases. This study aimed to investigate the neurotoxic potential of salt substitutes (Obu-Otoyo); salt A (made by burning palm kernel shaft then soaked in water overnight and the extract from the resulting residue is used as the salt substitute) and salt B (an unrefined salt mined from a local site at Ilobu town, Osun-State, Nigeria) by assessing their effect on some key enzymes linked with neurodegenerative disease [acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activities] as well as on malondialdehyde (MDA) content of the rat brain. Salt substitutes were fed to normal rats as dietary inclusion at doses of 0.5 and 1.0% for 30 days. Thereafter, the effect of the salt substitutes on AChE and BChE activities as well as on MDA level in the rat brain was determined. The results revealed that the salt substitutes caused a significant (p<0.05) increase in both AChE and BChE activity and also induced lipid peroxidation in the brain of rats in vivo as well as under in vitro condition in a dose-dependent manner. The effect of the salt substitutes on AChE and BChE activities could be attributed to the presence of some toxic heavy metals. Therefore, the ability of the salt substitutes to induce lipid peroxidation and activate AChE and BChE activities could provide some possible mechanism for their neurotoxic effect. PMID:27486373

  13. Local salt substitutes "Obu-otoyo" activate acetylcholinesterase and butyrylcholinesterase and induce lipid peroxidation in rat brain.

    PubMed

    Akinyemi, Ayodele J; Oboh, Ganiyu; Ademiluyi, Adedayo O

    2015-09-01

    Evidence has shown that ingestion of heavy metals can lead to neurodegenerative diseases. This study aimed to investigate the neurotoxic potential of salt substitutes (Obu-Otoyo); salt A (made by burning palm kernel shaft then soaked in water overnight and the extract from the resulting residue is used as the salt substitute) and salt B (an unrefined salt mined from a local site at Ilobu town, Osun-State, Nigeria) by assessing their effect on some key enzymes linked with neurodegenerative disease [acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activities] as well as on malondialdehyde (MDA) content of the rat brain. Salt substitutes were fed to normal rats as dietary inclusion at doses of 0.5 and 1.0% for 30 days. Thereafter, the effect of the salt substitutes on AChE and BChE activities as well as on MDA level in the rat brain was determined. The results revealed that the salt substitutes caused a significant (p<0.05) increase in both AChE and BChE activity and also induced lipid peroxidation in the brain of rats in vivo as well as under in vitro condition in a dose-dependent manner. The effect of the salt substitutes on AChE and BChE activities could be attributed to the presence of some toxic heavy metals. Therefore, the ability of the salt substitutes to induce lipid peroxidation and activate AChE and BChE activities could provide some possible mechanism for their neurotoxic effect.

  14. Altered binding of thioflavin t to the peripheral anionic site of acetylcholinesterase after phosphorylation of the active site by chlorpyrifos oxon or dichlorvos

    SciTech Connect

    Sultatos, L.G. Kaushik, R.

    2008-08-01

    The peripheral anionic site of acetylcholinesterase, when occupied by a ligand, is known to modulate reaction rates at the active site of this important enzyme. The current report utilized the peripheral anionic site specific fluorogenic probe thioflavin t to determine if the organophosphates chlorpyrifos oxon and dichlorvos bind to the peripheral anionic site of human recombinant acetylcholinesterase, since certain organophosphates display concentration-dependent kinetics when inhibiting this enzyme. Incubation of 3 nM acetylcholinesterase active sites with 50 nM or 2000 nM inhibitor altered both the B{sub max} and K{sub d} for thioflavin t binding to the peripheral anionic site. However, these changes resulted from phosphorylation of Ser203 since increasing either inhibitor from 50 nM to 2000 nM did not alter further thioflavin t binding kinetics. Moreover, the organophosphate-induced decrease in B{sub max} did not represent an actual reduction in binding sites, but instead likely resulted from conformational interactions between the acylation and peripheral anionic sites that led to a decrease in the rigidity of bound thioflavin t. A drop in fluorescence quantum yield, leading to an apparent decrease in B{sub max}, would accompany the decreased rigidity of bound thioflavin t molecules. The organophosphate-induced alterations in K{sub d} represented changes in binding affinity of thioflavin t, with diethylphosphorylation of Ser203 increasing K{sub d}, and dimethylphosphorylation of Ser203 decreasing K{sub d}. These results indicate that chlorpyrifos oxon and dichlorvos do not bind directly to the peripheral anionic site of acetylcholinesterase, but can affect binding to that site through phosphorylation of Ser203.

  15. In vitro anti-acetylcholinesterase activity of an aqueous extract of Unicaria tomentosa and in silico study of its active constituents

    PubMed Central

    Chowdhury, Suman; Shivani; Kumar, Suresh

    2016-01-01

    Depletion of acetylcholine in the central nervous system (CNS) is responsible for memory loss and cognition deficit. Enzyme acetylcholinesterase (AChE) is responsible for destruction of acetylcholine (Ach) in the brain. Many herbal plant extracts have been investigated for their potential use in the treatment of Alzheimer’s disease (AD) by inhibiting AChE and upregulating the levels of Ach. The current study investigated the anti-acetylcholinesterase (AChE) activity of an aqueous extract of Unicaria tomentosa bark which has not been reported so far in the literature. The in vitro study of an aqueous extract of U. tomentosa showed maximum inhibition of 76.2±0.002 % at 0.4mg/ml of final concentration with an IC50 = 0.112 mg/ml. The mechanism of inhibition was elucidated by kinetic study which showed mixed type of inhibition, this might be due to the presence of various phytoconstituents such as oxindole alkaloids present in an aqueous extract. Based on molecular structure of phytoconstituents obtained from U. tomentosa known from the relevant literature, in-silico molecular docking study was performed against AChE protein to validate the results. PMID:28149044

  16. In vitro anti-acetylcholinesterase activity of an aqueous extract of Unicaria tomentosa and in silico study of its active constituents.

    PubMed

    Chowdhury, Suman; Shivani; Kumar, Suresh

    2016-01-01

    Depletion of acetylcholine in the central nervous system (CNS) is responsible for memory loss and cognition deficit. Enzyme acetylcholinesterase (AChE) is responsible for destruction of acetylcholine (Ach) in the brain. Many herbal plant extracts have been investigated for their potential use in the treatment of Alzheimer's disease (AD) by inhibiting AChE and upregulating the levels of Ach. The current study investigated the anti-acetylcholinesterase (AChE) activity of an aqueous extract of Unicaria tomentosa bark which has not been reported so far in the literature. The in vitro study of an aqueous extract of U. tomentosa showed maximum inhibition of 76.2±0.002 % at 0.4mg/ml of final concentration with an IC50 = 0.112 mg/ml. The mechanism of inhibition was elucidated by kinetic study which showed mixed type of inhibition, this might be due to the presence of various phytoconstituents such as oxindole alkaloids present in an aqueous extract. Based on molecular structure of phytoconstituents obtained from U. tomentosa known from the relevant literature, in-silico molecular docking study was performed against AChE protein to validate the results.

  17. Acetylcholinesterase Inhibitors: Pharmacology and Toxicology

    PubMed Central

    Čolović, Mirjana B; Krstić, Danijela Z; Lazarević-Pašti, Tamara D; Bondžić, Aleksandra M; Vasić, Vesna M

    2013-01-01

    Acetylcholinesterase is involved in the termination of impulse transmission by rapid hydrolysis of the neurotransmitter acetylcholine in numerous cholinergic pathways in the central and peripheral nervous systems. The enzyme inactivation, induced by various inhibitors, leads to acetylcholine accumulation, hyperstimulation of nicotinic and muscarinic receptors, and disrupted neurotransmission. Hence, acetylcholinesterase inhibitors, interacting with the enzyme as their primary target, are applied as relevant drugs and toxins. This review presents an overview of toxicology and pharmacology of reversible and irreversible acetylcholinesterase inactivating compounds. In the case of reversible inhibitors being commonly applied in neurodegenerative disorders treatment, special attention is paid to currently approved drugs (donepezil, rivastigmine and galantamine) in the pharmacotherapy of Alzheimer’s disease, and toxic carbamates used as pesticides. Subsequently, mechanism of irreversible acetylcholinesterase inhibition induced by organophosphorus compounds (insecticides and nerve agents), and their specific and nonspecific toxic effects are described, as well as irreversible inhibitors having pharmacological implementation. In addition, the pharmacological treatment of intoxication caused by organophosphates is presented, with emphasis on oxime reactivators of the inhibited enzyme activity administering as causal drugs after the poisoning. Besides, organophosphorus and carbamate insecticides can be detoxified in mammals through enzymatic hydrolysis before they reach targets in the nervous system. Carboxylesterases most effectively decompose carbamates, whereas the most successful route of organophosphates detoxification is their degradation by corresponding phosphotriesterases. PMID:24179466

  18. Neuroprotective effects of quercetin on memory and anxiogenic-like behavior in diabetic rats: Role of ectonucleotidases and acetylcholinesterase activities.

    PubMed

    Maciel, Roberto M; Carvalho, Fabiano B; Olabiyi, Ayodeji A; Schmatz, Roberta; Gutierres, Jessié M; Stefanello, Naiara; Zanini, Daniela; Rosa, Michelle M; Andrade, Cinthia M; Rubin, Maribel A; Schetinger, Maria Rosa; Morsch, Vera Maria; Danesi, Cristiane C; Lopes, Sonia T A

    2016-12-01

    The present study investigated the protective effect of quercetin (Querc) on memory, anxiety-like behavior and impairment of ectonucleotidases and acetylcholinesterase (AChE) activities in brain of streptozotocin-induced diabetic rats (STZ-diabetes). The type 1 diabetes mellitus was induced by an intraperitoneal injection of 70mg/kg of streptozotocin (STZ), diluted in 0.1M sodium-citrate buffer (pH 4.5). Querc was dissolved in 25% ethanol and administered by gavage at the doses of 5, 25 and 50mg/kg once a day during 40days. The animals were distributed in eight groups of ten animals as follows: vehicle, Querc 5mg/kg, Querc 25mg/kg, Querc 50mg/kg, diabetes, diabetes plus Querc 5mg/kg, diabetes plus Querc 25mg/kg and diabetes plus Querc 50mg/kg. Querc was able to prevent the impairment of memory and the anxiogenic-like behavior induced by STZ-diabetes. In addition, Querc prevents the decrease in the NTPDase and increase in the adenosine deaminase (ADA) activities in SN from cerebral cortex of STZ-diabetes. STZ-diabetes increased the AChE activity in SN from cerebral cortex and hippocampus. Querc 50mg/kg was more effective to prevent the increase in AChE activity in the brain of STZ-diabetes. Querc also prevented an increase in the malondialdehyde levels in all the brain structures. In conclusion, the present findings showed that Querc could prevent the impairment of the enzymes that regulate the purinergic and cholinergic extracellular signaling and improve the memory and anxiety-like behavior induced by STZ-diabetes.

  19. Digestibility and Bioavailability of the Active Components of Erica australis L. Aqueous Extracts and Their Therapeutic Potential as Acetylcholinesterase Inhibitors

    PubMed Central

    Dias, Pilar; Falé, Pedro L.; Martins, Alice; Rauter, Amélia P.

    2015-01-01

    Erica australis L. (Ericaceae) is used in traditional medicine to treat many free-radical related ailments. In the present work, the stability and biological activity of the plant aqueous extracts submitted to an in vitro digestive process were investigated. Chemical stability was monitored by HPLC-DAD and LC-MS/MS, while the bioactivities were evaluated through the inhibition of acetylcholinesterase (AChE) and DPPH radical scavenging activity. Both extracts, whose main components were flavonol glycosides, inhibited AChE, showing IC50 values of 257.9 ± 6.2 µg/mL and 296.8 ± 8.8 µg/mL for the decoction and for the infusion, respectively. Significant radical scavenging activities were also revealed by both extracts, as denoted by the IC50 values for the decoction, 6.7 ± 0.1 µg/mL, and for the infusion, 10.5 ± 0.3 µg/mL. After submission to gastric and pancreatic juices, no remarkable alterations in the composition or in the bioactivities were observed, suggesting that the extracts may pass through the gastrointestinal tract, keeping their composition and therefore their biological properties. Moreover, the bioavailability of the components of both extracts, as studied in a Caco-2 cell model, showed that compounds can permeate the membrane, which is a condition to exert their biological activities. Our results add further support to the potential of E. australis for its antioxidant and neuroprotective properties. PMID:26347794

  20. In Vitro and In Vivo Metabolism and Inhibitory Activities of Vasicine, a Potent Acetylcholinesterase and Butyrylcholinesterase Inhibitor

    PubMed Central

    Liu, Wei; Shi, Xiaoyuan; Yang, Yadi; Cheng, Xuemei; Liu, Qing; Han, Han; Yang, Baohua; He, Chunyong; Wang, Yongli; Jiang, Bo; Wang, Zhengtao; Wang, Changhong

    2015-01-01

    Vasicine (VAS), a potential natural cholinesterase inhibitor, exhibited promising anticholinesterase activity in preclinical models and has been in development for treatment of Alzheimer’s disease. This study systematically investigated the in vitro and in vivo metabolism of VAS in rat using ultra performance liquid chromatography combined with electrospray ionization quadrupole time-of-flight mass spectrometry. A total of 72 metabolites were found based on a detailed analysis of their 1H- NMR and 13C NMR data. Six key metabolites were isolated from rat urine and elucidated as vasicinone, vasicinol, vasicinolone, 1,2,3,9-tetrahydropyrrolo [2,1-b] quinazolin-3-yl hydrogen sulfate, 9-oxo-1,2,3,9-tetrahydropyrrolo [2,1-b] quinazolin-3-yl hydrogen sulfate, and 1,2,3,9-tetrahydropyrrolo [2,1-b] quinazolin-3-β-D-glucuronide. The metabolic pathway of VAS in vivo and in vitro mainly involved monohydroxylation, dihydroxylation, trihydroxylation, oxidation, desaturation, sulfation, and glucuronidation. The main metabolic soft spots in the chemical structure of VAS were the 3-hydroxyl group and the C-9 site. All 72 metabolites were found in the urine sample, and 15, 25, 45, 18, and 11 metabolites were identified from rat feces, plasma, bile, rat liver microsomes, and rat primary hepatocyte incubations, respectively. Results indicated that renal clearance was the major excretion pathway of VAS. The acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities of VAS and its main metabolites were also evaluated. The results indicated that although most metabolites maintained potential inhibitory activity against AChE and BChE, but weaker than that of VAS. VAS undergoes metabolic inactivation process in vivo in respect to cholinesterase inhibitory activity. PMID:25849329

  1. Effects of chemical and thermal stress on acetylcholinesterase activity in the brain of the bank vole, Myodes glareolus.

    PubMed

    Świergosz-Kowalewska, Renata; Molenda, Patrycja; Halota, Anna

    2014-08-01

    One of the most important issues in ecotoxicology is better understanding the effects of interactions between chemical pollutants and physical environmental factors on animals. To fill this knowledge gap, changes in the activity of acetylcholinesterase (AChE) in the brain samples of bank voles Myodes (Clethrionomys) glareolus due to temperature effects, and two chemical stressors were studied in a full factorial laboratory experiment (27 treatments). The experiment was divided into three phases: acclimatisation (3 days), intoxication (42 days) and elimination (21 days). During the intoxication phase, animals were orally exposed to different concentrations of either nickel (0, 300 or 800 mg Ni/kg food), chlorpyrifos (CPF) (0, 50 or 350 mg CPF/kg food) or a mixture of both chemicals. During the acclimatisation and elimination phases, the bank voles were given uncontaminated food. The experiment was conducted at three different temperatures (10, 20 or 30 °C), and a 12 h:12 h light:dark regime. The animals were sacrificed at 0, 5, 10, 20, 42, 49 and 63 days after the beginning of the intoxication, and brain samples were obtained for chemical analysis. The nickel accumulation in the brain depended on the level of nickel exposure and on interactions between the temperature and other factors. Nickel exhibited no effect on AChE activity. In contrast, AChE was drastically inhibited by chlorpyrifos and low temperature, but interactions between all factors significantly influenced the enzyme activity during the elimination phase of the experiment. High mortality was observed in the groups exposed to high concentrations of nickel and chlorpyrifos.

  2. Acrylonitrile has Distinct Hormetic Effects on Acetyl-Cholinesterase Activity in Mouse Brain and Blood that are Modulated by Ethanol

    PubMed Central

    Yuanqing, He; Suhua, Wang; Guangwei, Xing; Chunlan, Ren; Hai, Qian; Wenrong, Xu; Rongzhu, Lu; Aschner, Michael; Milatovic, Dejan

    2013-01-01

    Acrylonitrile(AN) is a neurotoxin both in animals and humans, but its effects on acetylcholinesterase (AChE) activity remain controversial. This study aimed to determine the dose-response effects of AN on AChE activity and the modulatory role of ethanol pre-treatment. A total of 144 Kunming mice were randomly divided into 18 groups: nine groups received 5% ethanol in their drinking water, and the remaining nine groups received regular tap water. One week later, both the ethanol and tap water only groups were given an intraperitoneal injection of AN at the following doses: 0 (control), 0.156, 0.3125, 0.625, 1.25, 2.5, 5, 10 or 20 mg AN/kg body weight. AChE activity was determined on whole blood and brain 24 h later. Blood AChE activity was higher in AN-injected mice than in controls at all doses. AChE activity in blood increased in a dose-dependent manner, peaking at 0.156 mg/kg, after which a gradual decrease ensued, displaying a β-typed dose-response relationship. In contrast, brain AChE activity, following a single AN injection, was consistently lower than in control mice, and continued to fall up to a dose of 0.313 mg/kg, and thereafter increased gradually with higher doses. Mice receiving a 20 mg/kg dose of AN exhibited AChE brain activity indistinguishable from that of control mice, demonstrating a typical U-typed dose-response relationship. The activity of AChE in the blood and brain of the AN + ethanol-treated groups displayed a shift to the right, and the magnitude of the decrease in AChE activity induced by AN was attenuated relative to the AN-only group. These results suggest that AN affects AChE activity in both mouse blood and brain in a hormetic manner. Pretreatment with ethanol modifies the effect of AN on AChE, indicating that parent AN has a more prominent role than its metabolites in modulating enzyme activity. PMID:23550232

  3. Effects of intralipid and caffeic acid phenethyl ester on neurotoxicity, oxidative stress, and acetylcholinesterase activity in acute chlorpyriphos intoxication

    PubMed Central

    Ozkan, Umit; Osun, Arif; Basarslan, Kagan; Senol, Serkan; Kaplan, Ibrahim; Alp, Harun

    2014-01-01

    Chlorpyriphos is one of the most widely used organophosphate (OP) insecticide in agriculture with potential toxicity. Current post-exposure treatments consist of anti-cholinergic drugs and oxime compounds. We studied the effects of intralipid and caffeic acid phenethyl ester (CAPE) on chlorpyriphos toxicity to compose an alternative or supportive treatment for OP poisoning. Methods: Forty-nine rats were randomly divided into seven groups. Chlorpyriphos was administered for toxicity. Intralipid (IL) and CAPE administered immediately after chlorpyriphos. Serum acetylcholinesterase (AChE) level, total oxidant status (TOS), total antioxidant response (TAR), and histologic examination of cerebellum and brain tissue with Hematoxylin-Eosin and immunohistochemical dyes were examined. Results: Serum enzym levels showed that chlorpyriphos and CAPE inhibited AChE while IL alone had no effect, chlorpyriphos and CAPE intensifies the inhibition effect. Significant difference at AChE levels between the chlorpyriphos+IL and chlorpyriphos+CAPE verified that IL has a protective effect on AChE inhibition. TAR levels were significantly increased in all groups except chlorpyriphos group, TOS levels revealed that CAPE and IL decrease the amount of oxidative stress. Histologic examination revealed that neuronal degeneration was slightly decreased at chlorpyriphos+IL group, but CAPE had a significant effect on protection of neuronal degeneration. Conclusion: The results of this study gave us three key points. 1) AChE activity is important for diagnosis of OP intoxication but it has no value for determining the neuro-degeneration. 2) CAPE inhibits AChE activity and may increase the muscarinic-nicotinic hyperactivation. Therefore it should not be used for treatment of OP intoxication. 3) IL decreases the severity of neurodegeneration and symptoms of OP intoxication and it can be used as a supportive agent. PMID:24955152

  4. Galactose alters markers of oxidative stress and acetylcholinesterase activity in the cerebrum of rats: protective role of antioxidants.

    PubMed

    Delwing-de Lima, Daniela; Fröhlich, Monique; Dalmedico, Leticia; Aurélio, Juliana Gruenwaldt Maia; Delwing-Dal Magro, Débora; Pereira, Eduardo Manoel; Wyse, Angela T S

    2017-04-01

    We evaluated the in vitro effects of galactose at 0.1, 3.0, 5.0 and 10.0 mM on thiobarbituric acid-reactive substances (TBA-RS), total sulfhydryl content, protein carbonyl content, on the activities of the antioxidant enzymes catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and on acetylcholinesterase (AChE) activity in the cerebral cortex, cerebellum and hippocampus of rats. We also investigated the influence of the antioxidants (each at 1 mM), α-tocopherol, ascorbic acid and glutathione, on the effects elicited by galactose on the parameters tested. Results showed that galactose, at a concentration of 3.0 mM, enhanced TBA-RS levels in the hippocampus, cerebral cortex and cerebellum of rats. In the cerebral cortex, galactose at concentrations of 5.0 and 10.0 mM increased TBA-RS and protein carbonyl content, and at 10.0 mM increased CAT activity and decreased AChE activity. In the cerebellum, galactose at concentrations of 5.0 and 10.0 mM increased TBA-RS, SOD and GSH-Px activities. In the hippocampus, galactose at concentrations of 5.0 and 10.0 mM increased TBA-RS and CAT activity and at 10.0 mM decreased GSH-Px. Data showed that at the pathologically high concentration (greater than 5.0 mM), galactose induces lipid peroxidation, protein carbonylation, alters antioxidant defenses in the cerebrum, and also alters cholinesterase activity. Trolox, ascorbic acid and glutathione addition prevented the majority of alterations in oxidative stress parameters and the decrease in AChE activity that were caused by galactose. Our findings lend support to a potential therapeutic strategy for this condition, which may include the use of appropriate antioxidants for ameliorating the damage caused by galactose.

  5. Differences between male and female rhesus monkey erythrocyte acetylcholinesterase and plasma cholinesterase activity before and after exposure to sarin

    SciTech Connect

    Woodard, C.L.; Calamaio, C.A.; Kaminskis, A.; Anderson, D.R.; Harris, L.W.

    1993-05-13

    The female rhesus monkey has a menstrual cycle like the human. Additionally, several differences in enzyme levels between males and females and in the female during the menstrual cycle are present. Therefore we quantitated plasma cholinesterase (ChE/BuChE) and erythrocyte (RBC) acetylcholinesterase (AChE) activity before and after exposure to sarin (GB)(1 5 ug/kg, iv; a 0.75 LD50), in male and female rhesus (Macaca mulatta) monkeys. Twenty-eight-day preexposure baseline plasma ChE and RBC AChE values for six male and six female rhesus monkeys were compared for intra-animal, within sex and between sex differences. After these baseline values were obtained, the organophosphorus (OP) compound/Isopropyl methylphosphono-fluoridate (GB) was administered to atropinized monkeys to determine if there was a significant in vivo difference between the sexes in their response to this intoxication in regard to the rate of BuChE /AChE inhibition, pyridine-2-aldoxime methyl chloride (2-PAM) reactivation of the phosphonylated BuChE and the rate of aging of the phosphonylated:BuChE/AChE. In the pre-exposure portion of the protocol; the intra-animal and intra-group BuChE/AChE variations were found to be minimal; but there were significant differences between the male and female monkeys in both plasma BuChE and RBC AChE levels; although probably clinically insignificant in respect to an OP intoxication. No significant cyclic fluctuations were seen during the 28-day study in either sex.

  6. Flavanone Glycosides as Acetylcholinesterase Inhibitors: Computational and Experimental Evidence

    PubMed Central

    Remya, C.; Dileep, K. V.; Tintu, I.; Variyar, E. J.; Sadasivan, C.

    2014-01-01

    Acetylcholinesterase hydrolyzes the neurotransmitter called acetylcholine and is crucially involved in the regulation of neurotransmission. One of the observable facts in the neurodegenerative disorders like Alzheimer's disease is the decrease in the level of acetylcholine. Available drugs that are used for the treatment of Alzheimer's disease are primarily acetylcholinesterase inhibitors with multiple activities. They maintain the level of acetylcholine in the brain by inhibiting the acetylcholinesterase function. Hence acetylcholinesterase inhibitors can be used as lead compounds for the development of drugs against AD. In the present study, the binding potential of four flavanone glycosides such as naringin, hesperidin, poncirin and sakuranin against acetylcholinesterase was analysed by using the method of molecular modeling and docking. The activity of the top scored compound, naringin was further investigated by enzyme inhibition studies and its inhibitory concentration (IC50) towards acetylcholinesterase was also determined. PMID:25593395

  7. Is fast fiber innervation responsible for increased acetylcholinesterase activity in reinnervating soleus muscles?

    NASA Technical Reports Server (NTRS)

    Misulis, K. E.; Dettbarn, W. D.

    1985-01-01

    An investigation was conducted as to whether the predominantly slow SOL, which is low in AChE activity, is initially reinnervated by axons that originally innervated fast muscle fibers with high AChE activity, such as those of the EDL. Local denervation of the SOL in the guinea pig was performed because this muscle is composed solely of slow (type I) fibers; thereby virtually eliminating the possibility of homologous muscle fast fiber innervation. The overshoot in this preparation was qualitatively similar to that seen with distal denervation in the guinea pig and local and distal denervation in the rat. Thus, initial fast fiber innvervation is not responsible for the patterns of change in AChE activity seen with reinnervation in the SOL. It is concluded that the neural control of AChe is different in these two muscles and may reflect specific differences in the characteristics of AChE regulation in fast and slow muscle.

  8. Combined effects of chlorpyriphos, copper and temperature on acetylcholinesterase activity and toxicokinetics of the chemicals in the earthworm Eisenia fetida.

    PubMed

    Bednarska, Agnieszka J; Choczyński, Maciej; Laskowski, Ryszard; Walczak, Marcin

    2017-01-01

    In polluted environments organisms are commonly exposed to a combination of chemicals with different modes of action, and their effects can be additionally modified by natural abiotic conditions. One possible mechanism for interactions in mixtures is via toxicokinetics, as chemicals may alter the uptake, distribution, biotransformation and/or elimination of each other, and all these processes can be affected by temperature. In this study, the effect of temperature (T) on the toxicokinetics of copper (Cu) and chlorpyriphos (CHP), applied either singly or in binary mixtures, was studied in the earthworm Eisenia fetida. The experiments were conducted at 10 or 20 °C and the earthworms were exposed to environmentally realistic concentrations of Cu and/or CHP for 16 d, followed by a depuration period of 4 d in uncontaminated soil. The earthworms were sampled for body Cu and/or CHP concentrations and acetylcholinesterase (AChE) activity measurements. The CHP degradation rate in the soil was substantially higher at 20 °C and in soil treated with Cu. The significant (p < 0.05) inhibition of AChE activity in the earthworms exposed to CHP was found. The effect of Cu was significant only at p < 0.1. No synergistic effect of the parallel CHP and Cu exposure was found. Four days after transferring the earthworms to uncontaminated soil, the AChE activity recovered to the level observed in control animals. The temperature effect on the toxicokinetic parameters was more pronounced for CHP than for Cu. In the case of CHP, the assimilation rate constant (kA) was significantly higher at 20 °C than at 10 °C, both in CHP-only and CHP + Cu treatments. A similar trend was found for the elimination rate constant (kE), but the difference was statistically significant only for non-Cu treatments. In the case of Cu, the general trend of higher kA and kE at 20 °C and in the absence of CHP was observed.

  9. Acetylcholinesterase activity in intact and homogenized skeletal muscle of the frog.

    PubMed Central

    Miledi, R; Molenaar, P C; Polak, R L

    1984-01-01

    Enzymatic hydrolysis of acetylcholine (ACh) was determined in intact frog sartorius muscles or their homogenates. The Vmax was 29 nmol min-1 in intact muscles and 46 nmol min-1 per muscle in homogenates, and the Km was 6 and 0.2 mM, respectively. The muscle was divided into small segments, which were homogenized; the junctional cholinesterase (ChE) accounted for 60% of total enzyme activity. At low substrate concentrations the rate of hydrolysis was up to 30 times higher in homogenates than in intact muscles. This difference was greatly reduced at very high substrate concentrations. It appears that most of the ChE in intact muscle is 'occluded' to external ACh, mainly because the ChE at the edges of the synaptic cleft prevents the ACh from reaching the enzyme situated further inwards, which consequently does not contribute to its hydrolysis; homogenization makes all synaptic ChE accessible to added ACh. Incubation of sartorius muscles with collagenase caused an 80% decrease in ChE activity (determined in homogenates) of end-plate-containing parts which became similar to that in end-plate-free parts on which collagenase had little effect. Histochemistry showed that the tendon-muscle junction contained folds which were stained intensively for ChE. Diethyldimethylpyrophosphonate , neostigmine, eserine, and di-isopropyl fluorophosphonate inhibited ChE activity in this order of potency. The I50 values (i.e. the concentrations of the drugs which caused a 50% inhibition) were about 5 times higher in intact than in homogenized tissue. Neostigmine, 0.15 and 0.4 microM, increased the time constant of miniature end-plate currents 1.3- and 1.8-fold, and slowed down ChE activity of muscle homogenates by 1.4 and 2.1 times, respectively, without significantly affecting ACh hydrolysis by intact muscles. This indicates that synaptic ChE is not present in large excess. It is concluded that ChE activity measured in homogenates presents a better picture of in situ ChE activity than

  10. Neurotoxic responses in brain tissues of rainbow trout exposed to imidacloprid pesticide: Assessment of 8-hydroxy-2-deoxyguanosine activity, oxidative stress and acetylcholinesterase activity.

    PubMed

    Topal, Ahmet; Alak, Gonca; Ozkaraca, Mustafa; Yeltekin, Aslı Cilingir; Comaklı, Selim; Acıl, Gurdal; Kokturk, Mine; Atamanalp, Muhammed

    2017-05-01

    The extensive use of imidacloprid, a neonicotinoid insecticide, causes undesirable toxicity in non-targeted organisms including fish in aquatic environments. We investigated neurotoxic responses by observing 8-hydroxy-2-deoxyguanosine (8-OHdG) activity, oxidative stress and acetylcholinesterase (AChE) activity in rainbow trout brain tissue after 21 days of imidacloprid exposure at levels of (5 mg/L, 10 mg/L, 20 mg/L). The obtained results indicated that 8-OHdG activity did not change in fish exposed to 5 mg/L of imidacloprid, but 10 mg/L and 20 mg/L of imidacloprid significantly increased 8-OHdG activity compared to the control (p < 0.05). An immunopositiv reaction to 8-OHdG was detected in brain tissues. The brain tissues indicated a significant increase in antioxidant enzyme activities (superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx)) compared to the control and there was a significant increase in malondialdehyde (MDA) levels (p < 0.05). High concentrations of imidacloprid caused a significant decrease in AChE enzyme activity (p < 0.05). These results suggested that imidacloprid can be neurotoxic to fish by promoting AChE inhibition, an increase in 8-OHdG activity and changes in oxidative stress parameters. Therefore, these data may reflect one of the molecular pathways that play a role in imidacloprid toxicity.

  11. The Toxic Effect of Manganese on the Acetylcholinesterase Activity in Rat Brains

    PubMed Central

    Yousefi Babadi, Vahid; Sadeghi, Leila; Shirani, Kobra; Malekirad, Ali Akbar; Rezaei, Mohammad

    2014-01-01

    Manganese (Mn) is a naturally occurring element and an essential nutrient for humans and animals. However, exposure to high levels of Mn may cause neurotoxic effects. Accumulation of manganese damages central nervous system and causes Parkinson's disease-like syndrome called manganism. Mn neurotoxicity has been suggested to involve an imbalance between the DAergic and cholinergic systems. The pathological mechanisms associated with Mn neurotoxicity are poorly understood, but several reports have established it is mediated by changing of AChE activity that resulted in oxidative stress. Therefore we focused the effect of Mn in AChE activity in the rat's brain by MnCl2 injection intraperitoneally and analyzed their brains after time intervals. This study used different acute doses in short time course and different chronic doses at different exposing time to investigate which of them (exposing dose or time) is more important in Mn toxic effect. Results showed toxic effect of Mn is highly dose dependent and AChE activity in presence of chronic dose in 8 weeks reaches acute dose in only 2 days. PMID:25246936

  12. Effects of immature cashew nut-shell liquid (Anacardium occidentale) against oxidative damage in Saccharomyces cerevisiae and inhibition of acetylcholinesterase activity.

    PubMed

    De Lima, S G; Feitosa, C M; Citó, A M G L; Moita Neto, J M; Lopes, J A D; Leite, A S; Brito, M C; Dantas, S M M; Cavalcante, A A C Melo

    2008-09-09

    The cashew tree (Anacardium occidentale) represents one of the major cheapest sources of non-isoprenoid phenolic lipids, which have a variety of biological properties: they can act as molluscicides, insecticides, fungicides, have anti-termite properties, have medicinal applications, and demonstrate antioxidant activity in vitro. Immature cashew nut-shell liquid (iCNSL) is a unique natural source of unsaturated long-chain phenols. Their use has stimulated much research in order to prepare drug analogues for application in several fields. The objective of the present study was to determine whether iCNSL has antioxidant properties when used in strains of the yeast Saccharomyces cerevisiae and to measure the inhibitory activity of acetylcholinesterase. The constituents were identified using thin-layer chromatography, gas chromatography-mass spectrometry, Fourier transform infrared spectroscopy, and (1)H and (13)C nuclear magnetic resonance. The iCNSL contains anacardic acid, cardanol, cardol, and 2-methyl cardol. Immature cashew nut oil contains triacylglycerols, fatty acids, alkyl-substituted phenols, and cholesterol. The main constituents of the free fatty acids are palmitic (C(16:0)) and oleic acid (C(18:1)). iCNSL has excellent protective activities in strains of S. cerevisiae against oxidative damage induced by hydrogen peroxide and inhibits acetylcholinesterase activity. iCNSL may have an important role in protecting DNA against damage induced by reactive oxygen species, as well as hydrogen peroxide, generated by intra- and extracellular mechanisms.

  13. Active region seismology

    NASA Technical Reports Server (NTRS)

    Bogdan, Tom; Braun, D. C.

    1995-01-01

    Active region seismology is concerned with the determination and interpretation of the interaction of the solar acoustic oscillations with near-surface target structures, such as magnetic flux concentration, sunspots, and plage. Recent observations made with a high spatial resolution and a long temporal duration enabled measurements of the scattering matrix for sunspots and solar active regions to be carried out as a function of the mode properties. Based on this information, the amount of p-mode absorption, partial-wave phase shift, and mode mixing introduced by the sunspot, could be determined. In addition, the possibility of detecting the presence of completely submerged magnetic fields was raised, and new procedures for performing acoustic holography of the solar interior are being developed. The accumulating evidence points to the mode conversion of p-modes to various magneto-atmospheric waves within the magnetic flux concentration as being the unifying physical mechanism responsible for these diverse phenomena.

  14. Repetitive obidoxime treatment induced increase of red blood cell acetylcholinesterase activity even in a late phase of a severe methamidophos poisoning: A case report.

    PubMed

    Steinritz, Dirk; Eyer, Florian; Worek, Franz; Thiermann, Horst; John, Harald

    2016-02-26

    Accidental self-poisoning or deliberate use in suicidal intent of organophosphorus pesticides (OPP), which are widely used in agriculture, represent a health problem worldwide. Symptoms of poisoning are characterized by acute cholinergic crisis caused by inhibition of acetylcholinesterase. A 75-year-old male patient ingested 20ml of an OPP solution containing 10% methamidophos in suicidal intent. In the course of poisoning typical clinical symptoms of cholinergic crisis (miosis, bradycardia, hypotension, hypersalivation and impairment of neurologic status) were evident. Butyryl (plasma) cholinesterase (BChE) and red blood cell acetylcholinesterase (RBC-AChE) revealed decreased activities, thus specific treatment with the enzyme reactivator obidoxime was started. Inhibitory activity of the patient's plasma indicated significant amounts of persisting methamidophos in the circulation and was still found on day 4 after ingestion. Due to missing spontaneous breathing on day 6, obidoxime was administered again. Afterwards a significant increase of RBC-AChE activity was found. The patient was extubated on day 10 and a restitution ad integrum was achieved. In conclusion, obidoxime is a potent reactivator of OPP-inhibited AChE. A repetitive and prolonged administration of obidoxime should be considered in cases of severe methamidophos poisoning and should be tailored with an advanced analytical biomonitoring.

  15. A modification of thiocholine-ferricyanide method of Karnovsky and Roots for localization of acetylcholinesterase activity without interference by Koelle's copper thiocholine iodide precipitate.

    PubMed

    Tsuji, S; Larabi, Y

    1983-01-01

    In the original Karnovsky and Roots' method for the localization of acetylcholinesterase (AChE), thiocholine reduces the ferricyanide and cupric ions of this medium competitively, giving simultaneously cupric (Koelle's precipitate) as histochemical products. We modified the method in order to promote the true Karnovsky's reaction, and to slow down the secondary Koelle's reaction by increasing the concentration of the ferricyanide ion from 0.5 mM to 5.0 mM and by decreasing the concentration of the cupric ion from 3.0 mM to 2.5 mM. The cupric ion, complexed with 5 mM sodium citrate in the original method, was further stabilized by the use of 0.1 M citrate buffer in order to prevent the interaction of cupric ion with increased ferricyanide. In order to suppress completely the residual Koelle's precipitate, we used acetylthiocholine chloride as a substrate, instead of acetylthiocholine iodide. The chloride salt of cuprous thiocholine is soluble, contrary to the iodide salt. In addition, the pH of the medium was lowered from 6.0 to 5.0 to avoid artefactual nuclear staining, appearing at a pH beyond 5.5. In this modified medium, Karnovsky's cupric ferrocyanide becomes the sole precipitate at the enzymatic site and this provides fine localization of acetylcholinesterase activity.

  16. Design, synthesis and structure-activity relationships of dual inhibitors of acetylcholinesterase and serotonin transporter as potential agents for Alzheimer's disease.

    PubMed

    Toda, Narihiro; Tago, Keiko; Marumoto, Shinji; Takami, Kazuko; Ori, Mayuko; Yamada, Naho; Koyama, Kazuo; Naruto, Shunji; Abe, Kazumi; Yamazaki, Reina; Hara, Takao; Aoyagi, Atsushi; Abe, Yasuyuki; Kaneko, Tsugio; Kogen, Hiroshi

    2003-05-01

    We have designed and synthesized a dual inhibitor of acetylcholinesterase (AChE) and serotonin transporter (SERT) as a novel class of treatment drugs for Alzheimer's disease on the basis of a hypothetical model of the AChE active site. Dual inhibitions of AChE and SERT would bring about greater therapeutic effects than AChE inhibition alone and avoid adverse peripheral effects caused by excessive AChE inhibition. Compound (S)-6j exhibited potent inhibitory activities against AChE (IC(50)=101 nM) and SERT (IC(50)=42 nM). Furthermore, (S)-6j showed inhibitory activities of both AChE and SERT in mice brain following oral administration.

  17. Aphicidal Activity of Illicium verum Fruit Extracts and Their Effects on the Acetylcholinesterase and Glutathione S-transferases Activities in Myzus persicae (Hemiptera: Aphididae)

    PubMed Central

    Zhou, Ben-Guo; Wang, Sa; Dou, Ting-Ting; Liu, Su; Li, Mao-Ye; Hua, Ri-Mao; Li, Shi-Guang; Lin, Hua-Feng

    2016-01-01

    This study aims to explore the aphicidal activity and underlying mechanism of Illicium verum Hook. f. that is used as both food and medicine. The contact toxicity of the extracts from I. verum fruit with methyl alcohol (MA), ethyl acetate (EA), and petroleum ether (PE) against Myzus persicae (Sulzer), and the activities of acetylcholinesterase (AChE) and glutathione S-transferases (GSTs) of M. persicae after contact treatment were tested. The results showed that MA, EA, and PE extracts of 1.000 mg/l caused, respectively, M. persicae mortalities of 68.93%, 89.95% and 74.46%, and the LC50 of MA, EA, and PE extracts were 0.31, 0.14 and 0.27 mg/l at 72 h after treatment, respectively; the activities of AChE and GSTs in M. persicae were obviously inhibited by the three extracts, as compared with the control, with strong dose and time-dependent effects, the inhibition rates on the whole reached more than 50.00% at the concentration of 1.000 mg/l at 72 h after treatment. The inhibition of the extracts on AChE and GSTs activities (EA extract > PE extract > MA extract) were correlated with theirs contact toxic effects, so it is inferred that the decline of the metabolic enzymes activities may be one of important reasons of M. persicae death. The study results suggested that I. verum extracts have potential as a eco-friendly biopesticide in integrated pest management against M. persicae. PMID:26826651

  18. Zephycandidine A, the First Naturally Occurring Imidazo[1,2-f]phenanthridine Alkaloid from Zephyranthes candida, Exhibits Significant Anti-tumor and Anti-acetylcholinesterase Activities

    NASA Astrophysics Data System (ADS)

    Zhan, Guanqun; Qu, Xiaolan; Liu, Junjun; Tong, Qingyi; Zhou, Junfei; Sun, Bin; Yao, Guangmin

    2016-09-01

    Zephycandidine A (1), the first naturally occurring imidazo[1,2-f]phenanthridine alkaloid, was isolated from Zephyranthes candida (Amaryllidaceae). The structure of 1 was elucidated by spectroscopic analyses and NMR calculation, and a plausible biogenetic pathway for zephycandidine A (1) was proposed. Zephycandidine A (1) exhibited significant cytotoxicity against five cancer cell lines with IC50 values ranging from 1.98 to 7.03 μM with selectivity indices as high as 10 when compared to the normal Beas-2B cell. Further studies suggested that zephycandidine A (1) induces apoptosis in leukemia cells by the activation of caspase-3, upregulation of Bax, downregulation of Bcl-2, and degradation of PARP expression. In addition, zephycandidine A (1) showed acetylcholinesterase (AChE) inhibitory activity, and the docking studies of zephycandidine A (1) and galanthamine (2) with AChE revealed that interactions with W286 and Y337 are necessary.

  19. Zephycandidine A, the First Naturally Occurring Imidazo[1,2-f]phenanthridine Alkaloid from Zephyranthes candida, Exhibits Significant Anti-tumor and Anti-acetylcholinesterase Activities

    PubMed Central

    Zhan, Guanqun; Qu, Xiaolan; Liu, Junjun; Tong, Qingyi; Zhou, Junfei; Sun, Bin; Yao, Guangmin

    2016-01-01

    Zephycandidine A (1), the first naturally occurring imidazo[1,2-f]phenanthridine alkaloid, was isolated from Zephyranthes candida (Amaryllidaceae). The structure of 1 was elucidated by spectroscopic analyses and NMR calculation, and a plausible biogenetic pathway for zephycandidine A (1) was proposed. Zephycandidine A (1) exhibited significant cytotoxicity against five cancer cell lines with IC50 values ranging from 1.98 to 7.03 μM with selectivity indices as high as 10 when compared to the normal Beas-2B cell. Further studies suggested that zephycandidine A (1) induces apoptosis in leukemia cells by the activation of caspase-3, upregulation of Bax, downregulation of Bcl-2, and degradation of PARP expression. In addition, zephycandidine A (1) showed acetylcholinesterase (AChE) inhibitory activity, and the docking studies of zephycandidine A (1) and galanthamine (2) with AChE revealed that interactions with W286 and Y337 are necessary. PMID:27658482

  20. Use and disuse and the control of acetylcholinesterase activity in fast and slow twitch muscle of rat

    NASA Technical Reports Server (NTRS)

    Dettbarn, W. D.; Groswald, D.; Gupta, R. C.; Misulis, K. E.

    1985-01-01

    The role of acetylcholinesterase (AChE) in neuromuscular transmission is relatively well established, little is known, however, of the mechanisms that regulate its synthesis and control its specific distribution in fast and slow muscle. Innervation plays an important role in the regulation of AChE and elimination of the influence of the nerve by surgical denervation results in a loss of AChE. The influences of the nerve and how they are mediated was investigated. It is suggested that muscle usage and other factors such as materials carried by axonal transport may participate in the regulation of this enzyme. The mechanisms that regulate AChE and its molecular forms in two functionally different forms are studied.

  1. C- and O-glycosyl flavonoids in Sanguinello and Tarocco blood orange (Citrus sinensis (L.) Osbeck) juice: Identification and influence on antioxidant properties and acetylcholinesterase activity.

    PubMed

    Barreca, Davide; Gattuso, Giuseppe; Laganà, Giuseppina; Leuzzi, Ugo; Bellocco, Ersilia

    2016-04-01

    Sanguinello and Tarocco are the blood orange (Citrus sinensis (L.) Osbeck) cultivars most diffused worldwide. Reversed phase liquid chromatography coupled with MS-MS analysis showed that these two varieties have a similar chromatographic pattern, characterised by the presence of C- and O-glycosyl flavonoids. Of the two, Sanguinello was found to be far richer in flavonoids than Tarocco. In the juices, twelve individual components were identified for the first time, namely, four C-glycosyl flavones (lucenin-2, vicenin-2, stellarin-2, lucenin-2 4'-methyl ether and scoparin), three flavonol derivatives (quercetin-3-O-(2-rhamnosyl)-rutinoside, quercetin-3-O-hexoside, quercetin 3-hydroxy-3-methylglutaryl-glycoside), an O-triglycosyl flavanone (narirutin 4'-O-glucoside) and a flavone O-glycosides (chrysoeriol 7-O-neoesperidoside). Moreover, the influence of the identified C- and O-glycosyl flavonoids on the antioxidant and acetylcholinesterase activity of these juices has been evaluated.

  2. Immunocytochemical demonstration of axonal and perikaryal acetylcholinesterase in human cerebral cortex.

    PubMed

    Mesulam, M M; Geula, C; Cosgrove, R; Mash, D; Brimijoin, S

    1991-01-25

    The adult human neocortex contains a dense net of axons and perikarya which yield an acetylcholinesterase-rich enzymatic reaction pattern in histochemical experiments. We employed a monoclonal antibody to human acetylcholinesterase and a method for the concurrent visualization of histochemical and immunohistochemical reaction-products to explore the relationship between immunological and enzymatic markers of acetylcholinesterase. We observed that the cortical axons and perikarya with a histochemically determined acetylcholinesterase-rich enzymatic activity also contain acetylcholinesterase-like immunoreactivity. This was especially informative for the intracortical acetylcholinesterase-rich perikarya of layers III and V since these neurons require prolonged incubations for histochemical detection and since they are not conspicuous in other animal species. The availability of a reliable immunohistochemical method makes it possible to investigate the distribution of the acetylcholinesterase enzyme molecule independent of its enzymatic activity.

  3. Identical kinetics of human erythrocyte and muscle acetylcholinesterase with respect to carbamate pre-treatment, residual activity upon soman challenge and spontaneous reactivation after withdrawal of the inhibitors.

    PubMed

    Herkert, Nadja M; Eckert, Saskia; Eyer, Peter; Bumm, Rudolf; Weber, Georg; Thiermann, Horst; Worek, Franz

    2008-04-18

    The efficacy of oxime treatment in soman poisoning is limited due to rapid aging of inhibited acetylcholinesterase (AChE). Pre-treatment with carbamates was shown to improve antidotal treatment substantially. Recently, by using a dynamically working in vitro model with real-time determination of membrane-bound AChE activity, we were able to demonstrate that pre-inhibition of human erythrocyte AChE with pyridostigmine or physostigmine resulted in a markedly higher residual AChE activity after inhibition by soman or paraoxon than in the absence of reversible inhibitors. The purpose of the present study was to compare the effect of carbamate pre-treatment and soman challenge with human erythrocyte and muscle homogenate AChE. Both enzyme sources were immobilized on particle filters which were perfused with acetylthiocholine, Ellman's reagent and phosphate buffer. AChE activity was continuously analyzed in a flow-through detector. Pre-inhibition of AChE with pyridostigmine or physostigmine resulted in a concentration-dependent increase in carbamylation, residual activity after soman inhibition and fraction of decarbamylation AChE after discontinuation of the inhibitors without differences between human erythrocyte and muscle AChE. This data support the view that human erythrocyte AChE is an adequate surrogate marker for synaptic AChE in OP poisoning.

  4. Regional Activities Division. Papers.

    ERIC Educational Resources Information Center

    International Federation of Library Associations, The Hague (Netherlands).

    Papers on library network activities in Canada, the Third World, Japan, Malaysia, Brazil, and Sweden which were presented at the 1982 International Federation of Library Associations (IFLA) conference include: (1) "Canada: A Voluntary and Flexible Network," a review by Guy Sylvestre of the political, social, and economic structures…

  5. Highly Sensitive and Selective Immuno-capture/Electrochemical Assay of Acetylcholinesterase Activity in Red Blood Cells: A Biomarker of Exposure to Organophosphorus Pesticides and Nerve Agents

    SciTech Connect

    Chen, Aiqiong; Du, Dan; Lin, Yuehe

    2012-02-09

    Acetylcholinesterase (AChE) enzyme activity in red blood cells (RBCs) is a useful biomarker for biomonitoring of exposures to organophosphorus (OP) pesticides and chemical nerve agents. In this paper, we reported a new method for AChE activity assay based on selective immuno-capture of AChE from biological samples followed by enzyme activity assay of captured AChE using a disposable electrochemical sensor. The electrochemical sensor is based on multiwalled carbon nanotubes-gold nanocomposites (MWCNTs-Au) modified screen printed carbon electrode (SPCE). Upon the completion of immunoreaction, the target AChE (including active and inhibited) is captured onto the electrode surface and followed by an electrochemical detection of enzymatic activity in the presence of acetylthiocholine. A linear response is obtained over standard AChE concentration range from 0.1 to 10 nM. To demonstrate the capability of this new biomonitoring method, AChE solutions dosed with different concentration of paraoxon were used to validate the new AChE assay method. AChE inhibition in OP dosed solutions was proportional to its concentration from 0.2 to 50 nM. The new AChE activity assay method for biomonitoring of OP exposure was further validated with in-vitro paraoxon-dosed RBC samples. The established electrochemical sensing platform for AChE activity assay not only avoids the problem of overlapping substrate specificity with esterases by using selective antibody, but also eliminates potential interference from other electroactive species in biological samples. It offers a new approach for sensitive, selective, and rapid AChE activity assay for biomonitoring of exposures to OPs.

  6. Pharmacological characterization of RS-1259, an orally active dual inhibitor of acetylcholinesterase and serotonin transporter, in rodents: possible treatment of Alzheimer's disease.

    PubMed

    Abe, Yasuyuki; Aoyagi, Atsushi; Hara, Takao; Abe, Kazumi; Yamazaki, Reina; Kumagae, Yoshihiro; Naruto, Shunji; Koyama, Kazuo; Marumoto, Shinji; Tago, Keiko; Toda, Narihiro; Takami, Kazuko; Yamada, Naho; Ori, Mayuko; Kogen, Hiroshi; Kaneko, Tsugio

    2003-09-01

    A dual inhibitor of acetylcholinesterase (AChE) and serotonin transporter (SERT), RS-1259 (4-[1S)-methylamino-3-(4-nitrophenoxy)]propylphenyl N,N-dimethylcarbamate (fumaric acid)(1/2)salt), was newly synthesized. RS-1259 simultaneously inhibited AChE and SERT in the brain following an oral administration in mice and rats. Actual simultaneous elevation of extracellular levels of 5-HT and ACh in the rat hippocampus was confirmed by microdialysis. The compound was as effective as SERT inhibitors such as fluoxetine and fluvoxamine in a 5-hydroxytryptophan-enhancing test in mice. Spatial memory deficits in the two-platform task of a water maze in aged rats were ameliorated by RS-1259 as well as donepezil. Both RS-1259 and donepezil increased the awake episodes in the daytime electroencephalogram of rats. Although RS-1259 was weaker than donepezil in enhancing central cholinergic transmission, as observed by ACh elevation in the hippocampus and memory enhancement in aged rats, the efficacy of RS-1259 on the consciousness level, which reflects the whole activity in the brain, was almost the same as that of donepezil. These results suggest that both cholinergic and serotonergic systems are involved in maintaining brain arousal and that a dual inhibitor of AChE and SERT may be useful for the treatment of cognitive disorders associated with reduced brain activity such as in Alzheimer's disease.

  7. Kinetic analysis of interactions of different sarin and tabun analogues with human acetylcholinesterase and oximes: is there a structure-activity relationship?

    PubMed

    Aurbek, Nadine; Herkert, Nadja M; Koller, Marianne; Thiermann, Horst; Worek, Franz

    2010-09-06

    The repeated misuse of highly toxic organophosphorus compound (OP) based chemical warfare agents in military conflicts and terrorist attacks poses a continuous threat to the military and civilian sector. The toxic symptomatology of OP poisoning is mainly caused by inhibition of acetylcholinesterase (AChE, E.C. 3.1.1.7) resulting in generalized cholinergic crisis due to accumulation of the neurotransmitter acetylcholine (ACh) in synaptic clefts. Beside atropine as competitive antagonist of ACh at muscarinic ACh receptors oximes as reactivators of OP-inhibited AChE are a mainstay of standard antidotal treatment. However, human AChE inhibited by certain OP is rather resistant to oxime-induced reactivation. The development of more effective oxime-based reactivators may fill the gaps. To get more insight into a potential structure-activity relationship between human AChE, OPs and oximes in vitro studies were conducted to investigate interactions of different tabun and sarin analogues with human AChE and the oximes obidoxime and HI 6 by determination of various kinetic constants. Rate constants for the inhibition of human AChE by OPs, spontaneous dealkylation and reactivation as well as reactivation by obidoxime and HI 6 of OP-inhibited human AChE were determined. The recorded kinetic data did not allow a general statement concerning a structure-activity relationship between human AChE, OP and oximes.

  8. RNAi of ace1 and ace2 in Blattella germanica reveals their differential contribution to acetylcholinesterase activity and sensitivity to insecticides.

    PubMed

    Revuelta, L; Piulachs, M D; Bellés, X; Castañera, P; Ortego, F; Díaz-Ruíz, J R; Hernández-Crespo, P; Tenllado, F

    2009-12-01

    Cyclorrhapha insect genomes contain a single acetylcholinesterase (AChE) gene while other insects contain at least two ace genes (ace1 and ace2). In this study we tested the hypothesis that the two ace paralogous from Blattella germanica have different contributions to AChE activity, using RNA interference (RNAi) to knockdown each one individually. Paralogous-specific depletion of Bgace transcripts was evident in ganglia of injected cockroaches, although the effects at the protein level were less pronounced. Using spectrophotometric and zymogram measurements, we obtained evidence that BgAChE1 represents 65-75% of the total AChE activity in nerve tissue demonstrating that ace1 encodes a predominant AChE. A significant increase in sensitivity of Bgace1-interfered cockroaches was observed after 48 h of exposure to chlorpyrifos. In contrast, Bgace2 knockdown had a negligible effect on mortality to this organophosphate. These results point out a key role, qualitative and/or quantitative, of AChE1 as target of organophosphate insecticides in this species. Silencing the expression of Bgace1 but not Bgace2 also produced an increased mortality in insects when synergized with lambda-cyhalothrin, a situation which resembles the synergistic effects observed between organophosphates and pyrethroids. Gene silencing of ace genes by RNAi offers an exciting approach for examining a possible functional differentiation in ace paralogous.

  9. Synthesis, biological evaluation and molecular modeling of aloe-emodin derivatives as new acetylcholinesterase inhibitors.

    PubMed

    Shi, Da-Hua; Huang, Wei; Li, Chao; Wang, Ling-Ting; Wang, Shi-Fan

    2013-03-01

    A series of aloe-emodin derivatives were designed, synthesized and evaluated as acetylcholinesterase inhibitors. Most of the new prepared compounds showed remarkable acetylcholinesterase inhibitory activities. Among them, the compound 1-((4,5-dihydroxy-9,10-dioxo-9,10-dihydroanthracen-2-yl) methyl) pyridin-1-ium chloride (C3) which has a pyridinium substituent possessed the best inhibitory activity of acetylcholinesterase (IC(50)=0.09 μM). The docking study performed with AUTODOCK demonstrated that C3 could interact with the catalytic active site (CAS) and the peripheral anionic site (PAS) of acetylcholinesterase.

  10. Paper-based fluorescent sensor for rapid naked-eye detection of acetylcholinesterase activity and organophosphorus pesticides with high sensitivity and selectivity.

    PubMed

    Chang, Jiafu; Li, Haiyin; Hou, Ting; Li, Feng

    2016-12-15

    Various strategies have been proposed for the sensing of acetylcholinesterase (AChE) activity and organophosphorus pesticides (OPs). However, the practical application of most methods is restricted by their intrinsic drawbacks such as complexity, long analysis time, and high cost. Thus, it is highly desirable to develop simple, fast and sensitive approaches for AChE activity and OPs detection. Herein, we reported a simple paper-based fluorescent sensor (PFS) based on the aggregation induced emission (AIE) effect of tetraphenylethylene (TPE) and the addition reaction capability of maleimide, which has been used as a powerful tool for rapid naked-eye detection of AChE activity and OPs. The introduction of TPE provides the probe with unique fluorescence property in solid state and is of great importance for improving the sensitivity of PFS. The hydrolysis product of acetylthiocholine catalyzed by AChE induced the maleimide ring destruction and activated the fluorescence performance of TPE. Given that AChE activity can be specifically inhibited by OPs, the as-proposed PFS can also be utilized for sensitive detection of OPs. Meanwhile, the variation of fluorescence signal can be readily detected by naked eyes, and low detection limits of 2.5mUmL(-1) and 0.5ngmL(-1) for AChE activity and OPs are obtained, respectively. Moreover, it has been successfully applied for AChE activity and OPs detection in diluted human serum samples, showing its great potential to be applied in real samples. Thus, this strategy possesses considerable advantages of simplicity, rapid detection, portability, cost efficiency and visualization.

  11. Inhibition of acetylcholinesterase activity in the central nervous system of the red swamp crayfish, Procambarus clarkii, by mercury, cadmium, and lead

    SciTech Connect

    Devi, M.; Fingerman, M.

    1995-11-01

    The toxicological, physiological and biochemical responses of aquatic crustaceans to heavy metals have been reported by several investigators. Levels of glucose, lactic acid, sodium, potassium, aspartate aminotransferase and alanine aminotransferase in the blood of the crab Scylla serrata increased, while glycogen levels in hepatopancreas and muscle decreased after a four-week exposure to mercuric chloride. In fiddler crab, Uca pugilator, enzyme activity was observed to decrease in the hepatopancreas but increased in abdominal muscle after 48 hr cadmium exposure. In the red swamp crayfish, Procambarus clarkii, exposed for 96 hr to cadmium, glutahione (GSH) level and GSH S-transferase activity deceased in the midgut. In crayfish Astacus astacus exposed to sublethal concentrations of lead and cadmium, oxidative enzyme (succine dehydrogenase and NADPH-cytochrome P450 reductase) activities in gills and hepatopancrease decreased. Acetylcholinesterase (AChE) inhibition by organophosphates and organocarbamates in various crustaceans has bee reported. In vivo cadmium exposure caused increases in esterase activities, but mercury exposure decreases these activities in the hepatopancreas of the shrimp Callianassa tyrrhena. The freshwater crab, Barytelphusa guerini, exposed to 0.6 ppm cadmium showed reduced oxygen consumption throughout the experiment whereas AChE activity increased after 4 days but decreased after 15 days. The authors wanted to determine the effects of cadmium, lead and mercury on AChE activity in central nervous tissue of Procambarus clarkii. This enzyme has the potential for serving both as a biochemical indicator of toxic stress and a sensitive parameter for testing water for the presence of toxicants. These three biologically silent metals have, according to Schweinsberg and Karsa great toxicological significance to humans because their use is widespread. 14 refs., 4 figs.

  12. Maternal caffeine intake affects acetylcholinesterase in hippocampus of neonate rats.

    PubMed

    da Silva, Rosane Souza; Richetti, Stefânia Konrad; da Silveira, Vanessa Gass; Battastini, Ana Maria Oliveira; Bogo, Mauricio Reis; Lara, Diogo R; Bonan, Carla Denise

    2008-01-01

    Transcriptional factors and signalling molecules from intracellular metabolism modulate a complex set of events during brain development. Neurotransmitter and neuromodulator synthesis and their receptor expressions vary according to different stages of brain development. The dynamics of signalling systems is often accompanied by alterations in enzyme expression and activity. Adenosine is a neuromodulator that controls the release of several neurotransmitters, including acetylcholine, which is an important neurotransmitter during brain development. Caffeine is a non-specific antagonist of adenosine receptors and can reach the immature brain. We evaluated the effects of rat maternal caffeine intake (1g/L) on acetylcholine degradation and acetylcholinesterase expression from hippocampus of 7-, 14- and 21-day-old neonates in caffeine-treated and control groups. Caffeine was not able to change the age-dependent increase of acetylcholinesterase activity or the age-dependent decrease of acetylcholinesterase expression. However, caffeine promoted an increase of acetylcholinesterase activity (42%) without modifications on the level of acetylcholinesterase mRNA transcripts in 21-day-old rats. Considering the high score of phosphorylatable residues on acetylcholinesterase, this profile can be associated with a possible regulation by specific phosphorylation sites. These results highlight the ability of maternal caffeine intake to interfere on cholinergic neurotransmission during brain development.

  13. Effect of paraoxonase 1 192 Q/R polymorphism on paraoxonase and acetylcholinesterase enzyme activities in a Turkish population exposed to organophosphate.

    PubMed

    Sunay, Seda Zengin; Kayaaltı, Zeliha; Bayrak, Tülin; Söylemezoğlu, Tülin

    2015-12-01

    Organophosphate (OP) compounds are the most commonly used pesticide groups and they are commercially used in the market for local and industrial purposes. Paraoxonase 1 (PON1) enzyme plays an important role in biotransformation of OP compounds, which shows toxic effects via inhibiting the acetylcholinesterase (AChE). The aim of this study was to determine the effects of PON1 gene polymorphism and its effects on PON and AChE enzyme activities in individuals who were exposed to organophosphorus insecticides due to occupational reasons, and to profile the probability of susceptibility to organophosphorus compounds. For this purpose, 54 individuals who were exposed to OPs and 54 healthy unrelated controls were studied. First, PON1 and AChE enzyme activities were measured. Second, PON1 192 Q/R polymorphism was determined by standard polymerase chain reaction-restriction fragment length polymorphism technique. When the PON1 192 Q/R polymorphism was compared with PON1 enzyme activities, statistically significant association was found in both OP-exposed and control groups (p < 0.05). PON1 192 R(+) (QR + RR genotypes) genotype carriers had higher PON1 activities than 192 R(-) (QQ) genotype carriers. On the other hand, results were statistically analyzed in terms of AChE enzyme activities and there were statistically significant differences only in the OP-exposed group (p < 0.05). The mean AChE concentration in the OP-exposed group was determined as 33.79 ± 6.84 U/g haemoglobin (Hb) for PON1 192 R(+) carriers and 30.37 ± 7.62 U/g Hb for PON1 192 R(+) carriers. As a conclusion, PON1 and AChE activities were increasing according to the genotypes found in individuals having been exposed to OPs at a chronic level; 192 R(+) > 192 R(-), respectively.

  14. Fumigant toxicity and acetylcholinesterase inhibitory activity of 4 Asteraceae plant essential oils and their constituents against Japanese termite (Reticulitermes speratus Kolbe).

    PubMed

    Seo, Seon-Mi; Kim, Junheon; Kang, Jaesoon; Koh, Sang-Hyun; Ahn, Young-Joon; Kang, Kyu-Suk; Park, Il-Kwon

    2014-07-01

    This study investigated the fumigant toxicity of 4 Asteraceae plant essential oils and their constituents against the Japanese termite Reticulitermes speratus Kolbe. Fumigant toxicity varied with plant essential oils or constituents, exposure time, and concentration. Among the tested essential oils, those from Chamaemelum nobile exhibited the strongest fumigant toxicity, followed by those from Santolina chamaecyparissus, Ormenis multicaulis, and Eriocephalus punctulatus at 2 days after treatment. In all, 15, 24, 19, and 9 compounds were identified in the essential oils from C. nobile, E. punctulatus, O. multicaulis, and S. chamaecyparissus, respectively, by using gas chromatography, gas chromatography-mass spectrometry, or open-column chromatography. The identified compounds were tested individually for their fumigant toxicity against Japanese termites. Among the test compounds, trans-pinocarveol, caryophyllene oxide, sabinene hydrate, and santolina alcohol showed strong fumigant toxicity against Japanese termites. Acetylcholinesterase (AChE) inhibition activity of the identified compounds from C. nobile, E. punctulatus, O. multicaulis, and S. chamaecyparissus essential oils were tested to determine the mode of their action. The IC50 values of (+)-α-pinene, (-)-limonene, (-)-α-pinene, β-pinene, and β-phellandrene against Japanese termite AChE were 0.03, 0.13, 0.41, 0.42, and 0.67mg/mL, respectively. Further studies are warranted to determine the potential of these essential oils and their constituents as fumigants for termite control.

  15. Active Region Release Two CMEs

    NASA Video Gallery

    Solar material can be seen blowing off the sun in this video captured by NASA’s Solar Dynamics Observatory (SDO) on the night of Feb. 5, 2013. This active region on the sun sent out two coronal ...

  16. Phytoestrogens genistein and daidzin enhance the acetylcholinesterase activity of the rat pheochromocytoma cell line PC12 by binding to the estrogen receptor.

    PubMed

    Isoda, Hiroko; Talorete, Terence P N; Kimura, Momoko; Maekawa, Takaaki; Inamori, Yuhei; Nakajima, Nobuyoshi; Seki, Humitake

    2002-11-01

    Some compounds derived from plants have been known to possess estrogenic properties and can thus alter the physiology of higher organisms. Genistein and daidzin are examples of these phytoestrogens, which have recently been the subject of extensive research. In this study, genistein and daidzin were found to enhance the acetylcholinesterase (AChE) activity of the rat neuronal cell line PC12 at concentrations as low as 0.08 muM by binding to the estrogen receptor (ER). Results have shown that this enhancement was effectively blocked by the known estrogen receptor antagonist tamoxifen, indicating the involvement of the ER in AChE induction. That genistein and daidzin are estrogenic were confirmed in a cell proliferation assay using the human breast cancer cell line MCF7. This proliferation was also blocked by tamoxifen, again indicating the involvement of the ER. On the other hand, incubating the PC12 cells in increasing concentrations of 17 beta-estradiol (E2) did not lead to enhanced AChE activity, even in the presence of genistein or daidzin. This suggests that mere binding of an estrogenic compound to the ER does not necessarily lead to enhanced AChE activity. Moreover, the effect of the phytoestrogens on AChE activity cannot be expressed in the presence of E2 since they either could not compete with the natural ligand in binding to the ER or that E2 down-regulates its own receptor. This study clearly suggests that genistein and daidzin enhance AChE activityin PC12 cells by binding to the ER; however, the actual mechanism of enhancement is not known.

  17. Development of a dynamic model for real-time determination of membrane-bound acetylcholinesterase activity upon perfusion with inhibitors and reactivators.

    PubMed

    Eckert, Saskia; Eyer, Peter; Mückter, Harald; Worek, Franz

    2006-07-28

    Quantitative predictions of the course of acetylcholinesterase (AChE) activity, following interference of inhibitors and reactivators, are usually obscured by the time-dependent changes of all reaction partners. To mimic these dynamics we developed an in vitro model. Immobilized human erythrocyte ghosts in a bioreactor were continuously perfused while AChE activity was monitored by a modified Ellman method. The perfusion system consisted of two HPLC pumps with integrated quaternary low-pressure gradient formers that were programmed by a computer using commercial HPLC software. The combined eluates passed a particle filter (Millex-GS, 0.22 microm) containing a thin layer of erythrocytes that was immersed in a temperature-controlled water bath. The effluent passed a flow cell in a UV-vis detector, the signal of which was digitized, written to disc and calculated with curve fitting programs. AChE activity decreased by 3.4% within 2.5 h. The day-to-day variation of the freshly prepared bioreactor using the same enzyme source was +/-3.3%. Residual activity of 0.2% marked the limit of quantification. Following perfusion with paraoxon, pseudo first-order rate constants of inhibition were established that did not differ from results obtained in conventional assays. The same holds true for reactivation with obidoxime. The set-up presented allows freely programmable time-dependent changes of up to eight solvents to mimic pharmacokinetic profiles without accumulation of products. Due to some hysteresis in the system, reaction half-lives should be >3 min and concentration changes in critical compounds should exceed half-lives of 5 min. Otherwise, the system offers much flexibility and operates with high precision.

  18. Curcumin improves episodic memory in cadmium induced memory impairment through inhibition of acetylcholinesterase and adenosine deaminase activities in a rat model.

    PubMed

    Akinyemi, Ayodele Jacob; Okonkwo, Princess Kamsy; Faboya, Opeyemi Ayodeji; Onikanni, Sunday Amos; Fadaka, Adewale; Olayide, Israel; Akinyemi, Elizabeth Olufisayo; Oboh, Ganiyu

    2017-02-01

    Curcumin, the main polyphenolic component of turmeric (Curcuma longa) rhizomes has been reported to exert cognitive enhancing potential with limited scientific basis. Hence, this study sought to evaluate the effect of curcumin on cerebral cortex acetylcholinesterase (AChE) and adenosine deaminase (ADA) activities in cadmium (Cd)-induced memory impairment in rats. Animals were divided into six groups (n = 6): saline/vehicle, saline/curcumin 12.5 mg/kg, saline/curcumin 25 mg/kg, Cd/vehicle, Cd/curcumin 12.5 mg/kg, and Cd/curcumin 25 mg/kg. Rats received Cd (2.5 mg/kg) and curcumin (12.5 and 25 mg/kg, respectively) by gavage for 7 days. The results of this study revealed that cerebral cortex AChE and ADA activities were increased in Cd-poisoned rats, and curcumin co-treatment reversed these activities to the control levels. Furthermore, Cd intoxication increased the level of lipid peroxidation in cerebral cortex with a concomitant decreased in functional sulfuhydryl (-SH) group and nitric oxide (NO), a potent neurotransmitter and neuromodulatory agent. However, the co-treatment with curcumin at 12.5 and 25 mg/kg, respectively increased the non-enzymatic antioxidant status and NO in cerebral cortex with a decreased in malondialdehyde (MDA) level. Therefore, inhibition of AChE and ADA activities as well as increased antioxidant status by curcumin in Cd-induced memory dysfunction could suggest some possible mechanism of action for their cognitive enhancing properties.

  19. Irreversible thermal denaturation of Torpedo californica acetylcholinesterase.

    PubMed Central

    Kreimer, D. I.; Shnyrov, V. L.; Villar, E.; Silman, I.; Weiner, L.

    1995-01-01

    Thermal denaturation of Torpedo californica acetylcholinesterase, a disulfide-linked homodimer with 537 amino acids in each subunit, was studied by differential scanning calorimetry. It displays a single calorimetric peak that is completely irreversible, the shape and temperature maximum depending on the scan rate. Thus, thermal denaturation of acetylcholinesterase is an irreversible process, under kinetic control, which is described well by the two-state kinetic scheme N-->D, with activation energy 131 +/- 8 kcal/mol. Analysis of the kinetics of denaturation in the thermal transition temperature range, by monitoring loss of enzymic activity, yields activation energy of 121 +/- 20 kcal/mol, similar to the value obtained by differential scanning calorimetry. Thermally denatured acetylcholinesterase displays spectroscopic characteristics typical of a molten globule state, similar to those of partially unfolded enzyme obtained by modification with thiol-specific reagents. Evidence is presented that the partially unfolded states produced by the two different treatments are thermodynamically favored relative to the native state. PMID:8563632

  20. Effect of pharmaceuticals exposure on acetylcholinesterase (AchE) activity and on the expression of AchE gene in the monogonont rotifer, Brachionus koreanus.

    PubMed

    Rhee, Jae-Sung; Kim, Bo-Mi; Jeong, Chang-Bum; Park, Heum Gi; Leung, Kenneth Mei Yee; Lee, Young-Mi; Lee, Jae-Seong

    2013-11-01

    Pharmaceuticals are widely used in human and veterinary medicine. However, they are emerging as a significant contaminant in aquatic environments through wastewater. Due to the persistent and accumulated properties of pharmaceuticals via the food web, their potential harmful effects on aquatic animals are a great concern. In this study, we investigated the effects of six pharmaceuticals: acetaminophen, ATP; atenolol, ATN; carbamazepine, CBZ; oxytetracycline, OTC; sulfamethoxazole, SMX; and trimethoprim, TMP on acetylcholinesterase (AChE; EC 3.1.1.7) activity and its transcript expression with chlorpyrifos (as a positive control) in the monogonont rotifer, Brachionus koreanus. ATP, CBZ, and TMP exposure also remarkably inhibited Bk-AChE activity at 100 μg/L (24 h) and 1000 μg/L (12 h and 24 h). ATP, CBZ, and TMP exposure showed a significant decrease in the Bk-AChE mRNA level in a concentration-dependent manner. However, in the case of OTC and SMX, a slight decrease in Bk-AChE mRNA expression was found but only at the highest concentration. The time-course experiments showed that ATP positively induced Bk-AChE mRNA 12 h after exposure at both 100 and 1000 μg/L, while the Bk-AChE mRNA expression was significantly downregulated over 6 to 24 h after exposure to 1000 μg/L of CBZ, OTC, SMX, and TMP. Our findings suggest that Bk-AChE would be a useful biomarker for risk assessment of pharmaceutical compounds as an early signal of their toxicity in aquatic environments. Particularly, ATP, CBZ, and TMP may have a toxic cholinergic effect on rotifer B. koreanus by inhibiting AChE activity.

  1. Application of a dynamic in vitro model with real-time determination of acetylcholinesterase activity for the investigation of tabun analogues and oximes.

    PubMed

    Worek, Franz; Herkert, Nadja M; Koller, Marianne; Thiermann, Horst; Wille, Timo

    2015-12-25

    Tabun-inhibited acetylcholinesterase (AChE) is rather resistant towards reactivation by oximes in vitro while in vivo experiments showed some protection of animals poisoned by this chemical warfare nerve agent after treatment with an oxime and atropine. In addition, AChE inhibited by close tabun analogues, N,N-diethyltabun and N,N-di-n-propyltabun was completely resistant towards reactivation by oximes. In order to get more insight into potential mechanisms of this oxime resistance experiments with these toxic agents and the oximes obidoxime, 2-PAM, MMB-4 and HI-6 were performed utilizing a dynamic model with real-time determination of AChE activity. This experimental setup allowed the investigation of reactivation with minimized side reactions. The determined reactivation constants with tabun-inhibited human AChE were in good agreement with previously reported constants determined with a static model. N,N-diethyl- and N,N-di-n-propyltabun-inhibited human AChE could not be reactivated by oximes which indicates that the inadequate oxime effect was not due to re-inhibition by phosphonyloximes. Additional experiments with tabun-inhibited human and Rhesus monkey AChE revealed that no reactivation occurred with HI-6. These data give further support to the assumption that an interaction of tabun with residues in the active site gorge of AChE prevents effective reactivation by oximes, a mechanism which may also be the reason for the total oxime resistance of N,N-diethyl- and N,N-di-n-propyltabun-inhibited human AChE.

  2. Brain acetylcholinesterase activity in shiner perch (Cymatogaster aggregata) and juvenile chinook salmon (Oncorhynchus tshawytscha) after application of carbaryl to control burrowing shrimp within Willapa Bay, Washington.

    PubMed

    Troiano, Alexandra T; King, Kerensa A; Grue, Christian E; Grassley, James M; Ekblad, Cathy J

    2013-11-01

    Carbaryl has been applied in Willapa Bay, Washington, for five decades to control burrowing shrimp (Neotrypaea californiensis and Upogebia pugettensis) on commercial oyster (Crassostrea gigas) beds. Concerns about effects on nontarget species, including fishes, have led to restrictions in use despite a lack of data on in situ exposure. We measured brain acetylcholinesterase (AChE) activity in adult Shiner perch (Cymatogaster aggregata) and juvenile Chinook salmon (Oncorhynchus tshawytscha) after operational applications. We hypothesized that exposure in Shiner perch would be greater than in juvenile Chinook salmon because of their greater site fidelity and benthic foraging. However, Shiner perch exhibited no statistically significant AChE inhibition. Enzyme activity was statistically decreased (≤14 %) in juvenile Chinook salmon after a second spray event; however, inhibition was less than that associated with overt effects and was similar to controls by 48 h after the spray. Diet analyses confirmed that Shiner perch were primarily feeding on benthic invertebrates and that juvenile Chinook salmon were feeding primarily within the water column. Composition of Shiner perch diets and amount of food consumed varied little among channels and time periods; however, Shiner perch on beds consumed more food 6 h after application than those at other time points and locations. There were no consistent differences in the diets of juvenile Chinook salmon within channels among time periods. Results suggest (1) that carbaryl applications pose little hazard to fish in the bay having habitat and dietary preferences similar to those of Shiner perch and juvenile Chinook salmon and (2) that quantification of direct exposure in the field is essential to adequately assess risk.

  3. SDO Sees Active Region Outbursts

    NASA Video Gallery

    This close up video by NASA’s Solar Dynamics Observatory shows an active region near the right-hand edge of the sun’s disk, which erupted with at least a dozen minor events over a 30-hour period fr...

  4. In vitro biological assessment of berberis vulgaris and its active constituent, berberine: antioxidants, anti-acetylcholinesterase, anti-diabetic and anticancer effects

    PubMed Central

    2013-01-01

    Background Berberis vulgaris is a well known plant with traditional herbal medical history. The aims of this study was to bioscreen and compare the in vitro biological activity (antioxidant, cholinergic, antidaibetic and the anticancer) of barberry crude extract and berberine active compound. Methods The effect of B. vulgaris extract and berberine chloride on cellular thiobarbituric acid reactive species (TBARS) formation, diphenyle–α-picrylhydrazyl (DPPH) oxidation, cellular nitric oxide (NO) radical scavenging capability, superoxide dismutase (SOD), glutathione peroxidase (GPx), acetylcholinesterase (AChE) and α-gulcosidase activities were spectrophotometrically determined. On the other hand, the effect of extract and berberine as anticancer was estimated on three different cell lines which were MCF-7, HepG-2, and Caco-2 cells by using neutral red uptake assay which compared with control normal cells (PBMC). Results Our results showed that barberry crude extract contains 0.6 mg berberine/mg crude extract. Barberry extract showed potent antioxidative capacity through decreasing TBARS, NO and the oxidation of DPPH that associated with GPx and SOD hyperactivation. Inhibitory effect of berberis crude extract on α-glucosidase was more potent than that of berberine chloride, while both had the same AChE inhibitory effect. Besides, different concentrations of both berberine chloride and barberry ethanolic extract showed to have no growth inhibitory effect on normal blood cells (PBMC). Otherwise, both berberine chloride and barberry ethanolic extract showed to have inhibitory effect on the growth of breast, liver and colon cancer cell lines (MCF7, HepG2 and CACO-2, respectively) at different incubation times starting from 24 hrs up to 72 hrs and the inhibitory effect increased with time in a dose dependant manner. Conclusion This work demonstrates the potential of the barberry crude extract and its active alkaloid, berberine, on suppressing lipid peroxidation

  5. Oxidative stress and damage to erythrocytes in patients with chronic obstructive pulmonary disease--changes in ATPase and acetylcholinesterase activity.

    PubMed

    Bukowska, Bożena; Sicińska, Paulina; Pająk, Aneta; Koceva-Chyla, Aneta; Pietras, Tadeusz; Pszczółkowska, Anna; Górski, Paweł; Koter-Michalak, Maria

    2015-12-01

    The study indicates, for the first time, the changes in both ATPase and AChE activities in the membrane of red blood cells of patients diagnosed with COPD. Chronic obstructive pulmonary disease (COPD) is one of the most common and severe lung disorders. We examined the impact of COPD on redox balance and properties of the membrane of red blood cells. The study involved 30 patients with COPD and 18 healthy subjects. An increase in lipid peroxidation products and a decrease in the content of -SH groups in the membrane of red blood cells in patients with COPD were observed. Moreover, an increase in the activity of glutathione peroxidase and a decrease in superoxide dismutase, but not in catalase activity, were found as well. Significant changes in activities of erythrocyte membrane enzymes in COPD patients were also evident demonstrated by a considerably lowered ATPase activity and elevated AChE activity. Changes in the structure and function of red blood cells observed in COPD patients, together with changes in the activity of the key membrane enzymes (ATPases and AChE), can result from the imbalance of redox status of these cells due to extensive oxidative stress induced by COPD disease.

  6. A novel isopimarane diterpenoid with acetylcholinesterase inhibitory activity from Nepeta sorgerae, an endemic species to the Nemrut Mountain.

    PubMed

    Yilmaz, Anil; Cağlar, Pinar; Dirmenci, Tuncay; Gören, Nezhun; Topçu, Gülaçti

    2012-06-01

    From the dichloromethane extract of Nepeta sorgerae, the isolation and structure elucidation are now reported of a new isopimarane diterpenoid, named sorgerolone, and two known triterpenoids, oleanolic acid and ursolic acid. Antioxidant activity of the extracts and the isolated terpenoids was determined by the DPPH free radical scavenging and lipid peroxidation inhibition (beta-carotene bleaching) methods. Anticholinesterase activity of the extracts and isolates was investigated by Ellman's method against AChE and BChE enzymes. Although the antioxidant activity results were low, the AChE enzyme inhibition of the extracts and terpenoids was very promising.

  7. Impacts of oxidative stress on acetylcholinesterase transcription, and activity in embryos of zebrafish (Danio rerio) following Chlorpyrifos exposure.

    PubMed

    Rodríguez-Fuentes, Gabriela; Rubio-Escalante, Fernando J; Noreña-Barroso, Elsa; Escalante-Herrera, Karla S; Schlenk, Daniel

    2015-01-01

    Organophosphate pesticides cause irreversible inhibition of AChE which leads to neuronal overstimulation and death. Thus, dogma indicates that the target of OP pesticides is AChE, but many authors postulate that these compounds also disturb cellular redox processes, and change the activities of antioxidant enzymes. Interestingly, it has also been reported that oxidative stress plays also a role in the regulation and activity of AChE. The aims of this study were to determine the effects of the antioxidant, vitamin C (VC), the oxidant, t-butyl hydroperoxide (tBOOH) and the organophosphate Chlorpyrifos (CPF), on AChE gene transcription and activity in zebrafish embryos after 72h exposure. In addition, oxidative stress was evaluated by measuring antioxidant enzymes activities and transcription, and quantification of total glutathione. Apical effects on the development of zebrafish embryos were also measured. With the exception of AChE inhibition and enhanced gene expression, limited effects of CPF on oxidative stress and apical endpoints were found at this developmental stage. Addition of VC had little effect on oxidative stress or AChE, but increased pericardial area and heartbeat rate through an unknown mechanism. TBOOH diminished AChE gene expression and activity, and caused oxidative stress when administered alone. However, in combination with CPF, only reductions in AChE activity were observed with no significant changes in oxidative stress suggesting the adverse apical endpoints in the embryos may have been due to AChE inhibition by CPF rather than oxidative stress. These results give additional evidence to support the role of prooxidants in AChE activity and expression.

  8. Reduced Acetylcholine Receptor Density, Morphological Remodeling, and Butyrylcholinesterase Activity Can Sustain Muscle Function in Acetylcholinesterase Knockout Mice

    DTIC Science & Technology

    2004-09-01

    superior catalytic activity for mouse chow and water ad libitum and were 53 + 4 ACh hydrolysis, AChE is the dominant enzyme, days old at the time of...were analyzed using a two-tailed gain, 1593; scan time , 16 s). Endplates in the same Student’s t- test , whereas comparisons between three focal plane...amplitudes and prolonged knockout mice , this enzyme appears to exert a prom- rise and relaxation times similar to those observed in inent role in

  9. Decay of Solar Active Regions

    NASA Technical Reports Server (NTRS)

    Hathaway, David H.; Choudhary, Debi Prasad

    2005-01-01

    We examine the record of sunspot group areas observed over a period of 100 years to determine the rate of decay of solar active regions. We exclude observations of groups when they are more than 60deg in longitude from the central meridian and only include data when at least three days of observations are available following the date of maximum area for a spot group's disk passage. This leaves data for some 24,000 observations of active region decay. We find that the decay rate is a constant 20 microHem/day for spots smaller than about 200 microHem (about the size of a supergranule). This decay rate increases linearly to about 90 microHem/day for spots with areas of 1000 microHem. We find no evidence for significant variations in active region decay from one solar cycle to another. However, we do find that the decay rate is slower at lower latitudes. This gives a slower decay rate during the declining phase of sunspot cycles.

  10. Brain acetylcholinesterase activity recovery following acute methyl parathion intoxication in two feral rodent species: comparison to laboratory rodents

    SciTech Connect

    Roberts, D.K.; Silvey, N.J.; Bailey, E.M. Jr.

    1988-07-01

    Widespread use of organophosphorus insecticides (OPs) has produced both acute and chronic intoxication among nontarget organisms. Most such studies have included fish and birds as opposed to mammals. However, numerous OP toxicity studies have been conducted on laboratory rodents creating a temptation to apply this data to feral rodents. Chronic OP exposure has been reported to produce cholinergic adaptation which in turn lowers mortality rates following a subsequent acute anticholinesterase exposure. The relevance that these laboratory rodent studies have on feral rodents is subject to debate. Field studies involving OP exposure among nontarget feral mammals have produced contradictory results. Increased mortality as a result of repeated OP application has been reported. This observation may be of considerable importance to nontarget feral rodent populations due to the repetitive nature of OP application protocols. The ability of feral rodents to recover brain AChE activity (BAA) between OP application intervals undoubtedly promotes their survival. This study investigated and compared BAA recovery following acute oral methyl parathion intoxication among 2 feral rodent species and among 2 common laboratory rodent species.

  11. Novel assay utilizing fluorochrome-tagged physostigmine (Ph-F) to in situ detect active acetylcholinesterase (AChE) induced during apoptosis.

    PubMed

    Huang, Xuan; Lee, Brian; Johnson, Gary; Naleway, John; Guzikowski, Anthony; Dai, Wei; Darzynkiewicz, Zbigniew

    2005-01-01

    It was recently reported that acetylcholinesterase (AChE) is expressed in cells undergoing apoptosis and that its presence is essential for assembly of the apoptosome and subsequent caspase-9 activation. To obtain a marker of active AChE that could assay this enzyme in live intact cells and be applicable to fluorescence microscopy and cytometry, the fluorescein-tagged physostigmine (Ph-F), high affinity ligand (inhibitor) reactive with the active center of AChE, was constructed and tested for its ability to in situ label AChE and measure its induction during apoptosis. Ph-F inhibited cholinesterase activity in vitro (IC50 = 10(-6) and 5 x 10(-6) M for equine butyrylcholinesterase and human erythrocyte AChE, respectively) and was a selective marker of cells and structures that were AChE-positive. Thus, exposure of mouse bone marrow cells to Ph-F resulted in the exclusive labeling of megakaryocytes, and of the diaphragm muscle, preferential labeling of the nerve-muscle junctions (end-plates). During apoptosis of carcinoma HeLa cells and leukemic HL-60 or Jurkat cells triggered either by the DNA topoisomerase 1 inhibitor topotecan (TPT) or by oxidative stress (H2O2), the cells become reactive with Ph-F. Their Ph-F derived fluorescence was measured by flow and laser scanning cytometry. The appearance of Ph-F binding sites during apoptosis was preceded by the loss of mitochondrial potential, was concurrent with the presence of activated caspases, and was followed by loss of membrane integrity. At a very early stage of apoptosis, when nucleolar segregation was apparent, the Ph-F binding sites were distinctly localized within the nucleolus and at later stages of apoptosis in the cytoplasm. During apoptosis triggered by TPT, Ph-F binding was preferentially induced in S-phase cells. Our data on megakaryocytes and end-plates indicate that Ph-F reacts with active sites of AChE, and can be used to reveal the presence of this enzyme in live cells and possibly to study its

  12. Solar active region display system

    NASA Astrophysics Data System (ADS)

    Golightly, M.; Raben, V.; Weyland, M.

    2003-04-01

    The Solar Active Region Display System (SARDS) is a client-server application that automatically collects a wide range of solar data and displays it in a format easy for users to assimilate and interpret. Users can rapidly identify active regions of interest or concern from color-coded indicators that visually summarize each region's size, magnetic configuration, recent growth history, and recent flare and CME production. The active region information can be overlaid onto solar maps, multiple solar images, and solar difference images in orthographic, Mercator or cylindrical equidistant projections. Near real-time graphs display the GOES soft and hard x-ray flux, flare events, and daily F10.7 value as a function of time; color-coded indicators show current trends in soft x-ray flux, flare temperature, daily F10.7 flux, and x-ray flare occurrence. Through a separate window up to 4 real-time or static graphs can simultaneously display values of KP, AP, daily F10.7 flux, GOES soft and hard x-ray flux, GOES >10 and >100 MeV proton flux, and Thule neutron monitor count rate. Climatologic displays use color-valued cells to show F10.7 and AP values as a function of Carrington/Bartel's rotation sequences - this format allows users to detect recurrent patterns in solar and geomagnetic activity as well as variations in activity levels over multiple solar cycles. Users can customize many of the display and graph features; all displays can be printed or copied to the system's clipboard for "pasting" into other applications. The system obtains and stores space weather data and images from sources such as the NOAA Space Environment Center, NOAA National Geophysical Data Center, the joint ESA/NASA SOHO spacecraft, and the Kitt Peak National Solar Observatory, and can be extended to include other data series and image sources. Data and images retrieved from the system's database are converted to XML and transported from a central server using HTTP and SOAP protocols, allowing

  13. Exploring the Effect of Phyllanthus emblica L. on Cognitive Performance, Brain Antioxidant Markers and Acetylcholinesterase Activity in Rats: Promising Natural Gift for the Mitigation of Alzheimer's Disease

    PubMed Central

    Uddin, Md. Sahab; Mamun, Abdullah Al; Hossain, Md. Sarwar; Akter, Farjana; Iqbal, Mohammed Ashraful; Asaduzzaman, Md.

    2016-01-01

    Neurodegenerative diseases are incurable and debilitating conditions that result in the progressive degeneration of nerve cells, which affect the cognitive activity. Currently, as a result of multiple studies linking Alzheimer's disease (AD) to oxidative damage, the uses of natural antioxidant to prevent, delay, or enhance the pathological changes underlying the progression of AD has received considerable attention. Therefore, this study was aimed at examining the effect of ethanolic extracts of Phyllanthus emblica (EEPE) ripe (EEPEr) and EEPE unripe (EEPEu) fruits on cognitive functions, brain antioxidant enzymes, and acetylcholinesterase (AChE) activity in rat. The effects of EEPEr and EEPEu fruits (i.e., 100 and 200 mg/kg b.w.) were examined in Swiss albino male rats for 12 days and its effect on cognitive functions, brain antioxidant enzymes, and AChE activity determined. Learning and memory enhancing activity of EEPE fruit was examined by using passive avoidance test and rewarded alternation test. Antioxidant potentiality was evaluated by measuring the activity of antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione reductase, reduced glutathione (GSH), glutathione-S-transferase, and the contents of thiobarbituric acid reactive substances (TBARS) in entire brain tissue homogenates. AChE activity was determined using colorimetric method. Administration of the highest dose (i.e., 200 mg/kg b.w.) of EEPEr fruit significantly (p < 0.01) and both lowest and highest doses (i.e., 100 and 200 mg/kg b.w.) of EEPEu fruit markedly (p < 0.05, p < 0.001) increased step-through latency in rats on 6th, 11th, and 12th day with respect to the control group. For aforementioned doses, the percentage of memory retention (MR) was considerably (p < 0.05, p < 0.01) increased in rats on 10th, 11th, and 12th days with respect to the control group. The extract, particularly highest dose (i.e., 200 mg/kg b.w.) of EEPEr

  14. Exploring the Effect of Phyllanthus emblica L. on Cognitive Performance, Brain Antioxidant Markers and Acetylcholinesterase Activity in Rats: Promising Natural Gift for the Mitigation of Alzheimer's Disease.

    PubMed

    Uddin, Md Sahab; Mamun, Abdullah Al; Hossain, Md Sarwar; Akter, Farjana; Iqbal, Mohammed Ashraful; Asaduzzaman, Md

    2016-10-01

    Neurodegenerative diseases are incurable and debilitating conditions that result in the progressive degeneration of nerve cells, which affect the cognitive activity. Currently, as a result of multiple studies linking Alzheimer's disease (AD) to oxidative damage, the uses of natural antioxidant to prevent, delay, or enhance the pathological changes underlying the progression of AD has received considerable attention. Therefore, this study was aimed at examining the effect of ethanolic extracts of Phyllanthus emblica (EEPE) ripe (EEPEr) and EEPE unripe (EEPEu) fruits on cognitive functions, brain antioxidant enzymes, and acetylcholinesterase (AChE) activity in rat. The effects of EEPEr and EEPEu fruits (i.e., 100 and 200 mg/kg b.w.) were examined in Swiss albino male rats for 12 days and its effect on cognitive functions, brain antioxidant enzymes, and AChE activity determined. Learning and memory enhancing activity of EEPE fruit was examined by using passive avoidance test and rewarded alternation test. Antioxidant potentiality was evaluated by measuring the activity of antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione reductase, reduced glutathione (GSH), glutathione-S-transferase, and the contents of thiobarbituric acid reactive substances (TBARS) in entire brain tissue homogenates. AChE activity was determined using colorimetric method. Administration of the highest dose (i.e., 200 mg/kg b.w.) of EEPEr fruit significantly (p < 0.01) and both lowest and highest doses (i.e., 100 and 200 mg/kg b.w.) of EEPEu fruit markedly (p < 0.05, p < 0.001) increased step-through latency in rats on 6th, 11th, and 12th day with respect to the control group. For aforementioned doses, the percentage of memory retention (MR) was considerably (p < 0.05, p < 0.01) increased in rats on 10th, 11th, and 12th days with respect to the control group. The extract, particularly highest dose (i.e., 200 mg/kg b.w.) of EEPEr

  15. An acetylcholinesterase-inspired biomimetic toxicity sensor.

    PubMed

    Wujcik, Evan K; Londoño, Nicolas J; Duirk, Stephen E; Monty, Chelsea N; Masel, Richard I

    2013-05-01

    This work demonstrates the ability of an acetylcholinesterase-inspired biomimetic sensor to accurately predict the toxicity of acetylcholinesterase (AChE) inhibitors. In surface waters used for municipal drinking water supplies, numerous pesticides and other anthropogenic chemicals have been found that inhibit AChE; however, there is currently no portable toxicity assay capable of determining the potential neurotoxicity of water samples and complex mixtures. Biological assays have been developed to determine the toxicity of unknown samples, but the short shelf-life of cells and other biological materials often make them undesirable for use in portable assays. Chemical methods and structure-activity-relationships, on the other hand, require prior knowledge on the compounds of interest that is often unavailable when analyzing environmental samples. In the toxicity assay presented here, the acetylcholinesterase enzyme has been replaced with 1-phenyl-1,2,3-butanetrione 2-oxime (PBO) a biomimetic compound that is structurally similar to the AChE active site. Using a biomimetic compound in place of the native enzyme allows for a longer shelf-life while maintaining the selective and kinetic ability of the enzyme itself. Previous work has shown the success of oxime-based sensors in the selective detection of AChE inhibitors and this work highlights the ability of an AChE-inspired biomimetic sensor to accurately predict the toxicity (LD50 and LC50) for a range of AChE inhibitors. The biomimetic assay shows strong linear correlations to LD50 (oral, rat) and LC50 (fish) values. Using a test set of eight AChE inhibitors, the biomimetic assay accurately predicted the LC50 value for 75% of the inhibitors within one order of magnitude.

  16. Inhibition of acetylcholinesterase by Tea Tree oil.

    PubMed

    Mills, Clive; Cleary, Brian J; Gilmer, John F; Walsh, John J

    2004-03-01

    Pediculosis is a widespread condition reported in schoolchildren. Treatment most commonly involves the physical removal of nits using fine-toothcombs and the chemical treatment of adult lice and eggs with topical preparations. The active constituents of these preparations frequently exert their effects through inhibition of acetylcholinesterase (AChE, EC 3.1.1.7). Increasing resistance to many preparations has led to the search for more effective treatments. Tea Tree oil, otherwise known as Melaleuca oil, has been added to several preparations as an alternative treatment of head lice infestations. In this study two major constituents of Tea Tree oil, 1,8-cineole and terpinen-4-ol, were shown to inhibit acetylcholinesterase at IC50 values (inhibitor concentrations required to give 50% inhibition) of 0.04 and 10.30 mM, respectively. Four samples of Tea Tree oil tested (Tisserand, Body Treats, Main Camp and Irish Health Culture Association Pure Undiluted) showed anticholinesterase activity at IC50 values of 0.05, 0.10, 0.08 and 0.11 microL mL(-1), respectively. The results supported the hypothesis that the insecticidal activity of Tea Tree oil was attributable, in part, to the anticholinesterase activity of Tea Tree oil.

  17. Laboratory and Simulated Field Bioassays to Evaluate Larvicidal Activity of Pinus densiflora Hydrodistillate, Its Constituents and Structurally Related Compounds against Aedes albopictus, Aedes aegypti and Culex pipiens pallens in Relation to Their Inhibitory Effects on Acetylcholinesterase Activity.

    PubMed

    Lee, Dong Chan; Ahn, Young-Joon

    2013-05-30

    The toxicity of Pinus densiflora (red pine) hydrodistillate, its 19 constituents and 28 structurally related compounds against early third-instar larvae of Aedes albopictus (Ae. albopictus), Aedes aegypti (Ae. aegypti) and Culex pipiens palles (Cx. p. pallens) was examined using direct-contact bioassays. The efficacy of active compounds was further evaluated in semi-field bioassays using field-collected larval Cx. p. pallens. Results were compared with those of two synthetic larvicides, temephos and fenthion. In laboratory bioassays, Pinus densiflora hydrodistillate was found to have 24 h LC50 values of 20.33, 21.01 and 22.36 mg/L against larval Ae. albopictus, Ae. aegypti and Cx. p. pallens respectively. Among the identified compounds, thymol, δ-3-carene and (+)-limonene exhibited the highest toxicity against all three mosquito species. These active compounds were found to be nearly equally effective in field trials as well. In vitro bioassays were conducted to examine the acetylcholinesterase (AChE) inhibitory activity of 10 selected compounds. Results showed that there is a noticeable correlation between larvicidal activity and AChE inhibitory activity. In light of global efforts to find alternatives for currently used insecticides against disease vector mosquitoes, Pinus densiflora hydrodistillate and its constituents merit further research as potential mosquito larvicides.

  18. The recovery of acetylcholinesterase activity and the progression of neuropathological and pathophysiological alterations in the rat basolateral amygdala after soman-induced status epilepticus: relation to anxiety-like behavior

    PubMed Central

    Prager, Eric M.; Aroniadou-Anderjaska, Vassiliki; Almeida-Suhett, Camila P.; Figueiredo, Taiza H.; Apland, James P.; Rossetti, Franco; Olsen, Cara H.; Braga, Maria F.M.

    2014-01-01

    Organophosphorus nerve agents are powerful neurotoxins that irreversibly inhibit acetylcholinesterase (AChE) activity. One of the consequences of AChE inhibition is the generation of seizures and status epilepticus (SE), which cause brain damage, resulting in long-term neurological and behavioral deficits. Increased anxiety is the most common behavioral abnormality after nerve agent exposure. This is not surprising considering that the amygdala, and the basolateral nucleus of the amygdala (BLA) in particular, plays a central role in anxiety, and this structure suffers severe damage by nerve agent-induced seizures. In the present study, we exposed male rats to lethal doses of the nerve agent soman, and determined the time course of recovery of AChE activity, along with the progression of neuropathological and pathophysiological alterations in the BLA, during a 30-day period after exposure. Measurements were taken at 24 hours, 7 days, 14 days, and 30 days after exposure, and at 14 and 30 days, anxiety-like behavior was also evaluated. We found that more than 90% of AChE is inhibited at the onset of SE, and AChE inhibition remains at this level 24 hours later, in the BLA, as well as in the hippocampus, piriform cortex, and prelimbic cortex, which we analyzed for comparison. AChE activity recovered by day 7 in the BLA and day 14 in the other three regions. Significant neuronal loss and neurodegeneration were present in the BLA at 24 hours and throughout the 30-day period. There was no significant loss of GABAergic interneurons in the BLA at 24 hours post-exposure. However, by day 7, the number of GABAergic interneurons in the BLA was reduced, and at 14 and 30 days after soman, the ratio of GABAergic interneurons to the total number of neurons was lower compared to controls. Anxiety-like behavior in the open-field and the acoustic startle response tests was increased at 14 and 30 days post-exposure. Accompanying pathophysiological alterations in the BLA – studied in

  19. Novel multipotent tacrine-dihydropyridine hybrids with improved acetylcholinesterase inhibitory and neuroprotective activities as potential drugs for the treatment of Alzheimer's disease.

    PubMed

    Marco-Contelles, José; León, Rafael; de Los Ríos, Cristóbal; Guglietta, Antonio; Terencio, José; López, Manuela G; García, Antonio G; Villarroya, Mercedes

    2006-12-28

    In this work we describe the synthesis and biological evaluation of the tacrine-1,4-dihydropyridine (DHP) hybrids (3-11). These multipotent molecules are the result of the juxtaposition of an acetylcholinesterase inhibitor (AChEI) such as tacrine (1) and a 1,4-DHP such as nimodipine (2). Compounds 3-11 are very selective and potent AChEIs and show an excellent neuroprotective profile and a moderate Ca2+ channel blockade effect. Consequently, these molecules are new potential drugs for the treatment of Alzheimer's disease.

  20. Evolution of active region outflows throughout an active region lifetime

    NASA Astrophysics Data System (ADS)

    Zangrilli, L.; Poletto, G.

    2016-10-01

    Context. We have shown previously that SOHO/UVCS data allow us to detect active region (AR) outflows at coronal altitudes higher than those reached by other instrumentation. These outflows are thought to be a component of the slow solar wind. Aims: Our purpose is to study the evolution of the outflows in the intermediate corona from AR 8100, from the time the AR first forms until it dissolves, after several transits at the solar limb. Methods: Data acquired by SOHO/UVCS at the time of the AR limb transits, at medium latitudes and at altitudes ranging from 1.5 to 2.3 R⊙, were used to infer the physical properties of the outflows through the AR evolution. To this end, we applied the Doppler dimming technique to UVCS spectra. These spectra include the H i Lyα line and the O vi doublet lines at 1031.9 and 1037.6 Å. Results: Plasma speeds and electron densities of the outflows were inferred over several rotations of the Sun. AR outflows are present in the newly born AR and persist throughout the entire AR life. Moreover, we found two types of outflows at different latitudes, both possibly originating in the same negative polarity area of the AR. We also analyzed the behavior of the Si xii 520 Å line along the UVCS slit in an attempt to reveal changes in the Si abundance when different regions are traversed. Although we found some evidence for a Si enrichment in the AR outflows, alternative interpretations are also plausible. Conclusions: Our results demonstrate that outflows from ARs are detectable in the intermediate corona throughout the whole AR lifetime. This confirms that outflows contribute to the slow wind.

  1. Syntheses of coumarin-tacrine hybrids as dual-site acetylcholinesterase inhibitors and their activity against butylcholinesterase, Aβ aggregation, and β-secretase.

    PubMed

    Sun, Qi; Peng, Da-Yong; Yang, Sheng-Gang; Zhu, Xiao-Lei; Yang, Wen-Chao; Yang, Guang-Fu

    2014-09-01

    Exploring small-molecule acetylcholinesterase (AChE) inhibitors to slow the breakdown of acetylcholine (Ach) represents the mainstream direction for Alzheimer's disease (AD) therapy. As the first acetylcholinesterase inhibitor approved for the clinical treatment of AD, tacrine has been widely used as a pharmacophore to design hybrid compounds in order to combine its potent AChE inhibition with other multi-target profiles. In present study, a series of novel tacrine-coumarin hybrids were designed, synthesized and evaluated as potent dual-site AChE inhibitors. Moreover, compound 1g was identified as the most potent candidate with about 2-fold higher potency (Ki=16.7nM) against human AChE and about 2-fold lower potency (Ki=16.1nM) against BChE than tacrine (Ki=35.7nM for AChE, Ki=8.7nM for BChE), respectively. In addition, some of the tacrine-coumarin hybrids showed simultaneous inhibitory effects against both Aβ aggregation and β-secretase. We therefore conclude that tacrine-coumarin hybrid is an interesting multifunctional lead for the AD drug discovery.

  2. Genetic factors potentially reducing fitness cost of organophosphate-insensitive acetylcholinesterase(s) in Rhipicephalus (Boophilus) microplus (Acari: Ixodidae)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Acaricidal activity of organophosphate (OP) and carbamate acaricides is believed to result from inhibition of acetylcholinesterase (AChE). Previous studies in Rhipicephalus (Boophilus) microplus demonstrated the presence of three presumptive AChE genes (BmAChEs). Biochemical characterization of re...

  3. Effects of Sequential Applications of Bassa 50EC (Fenobucarb) and Vitashield 40EC (Chlorpyrifos ethyl) on Acetylcholinesterase Activity in Climbing Perch (Anabas testudineus) Cultured in Rice Fields in the Mekong Delta, Vietnam.

    PubMed

    Tam, Nguyen Thanh; Berg, Håkan; Laureus, Jenny; Cong, Nguyen Van; Tedengren, Michael

    2016-07-01

    This study assesses the effects of sequential applications of the insecticides Bassa 50EC (fenobucarb-F) and Vitashield 40EC (chlorpyrifos ethyl-CPF), sprayed at concentrations used by rice farmers in the Mekong Delta, on the brain acetylcholinesterase (AChE) in climbing perch fingerlings. After spraying the pesticides on the rice fields, the water concentrations of both insecticides decreased below the detection levels within 3 days. The sequential applications caused significant inhibition on the brain AChE activity in the exposed fish. The inhibition by F was quicker, but less prolonged, than for CPF. The inhibition levels caused by the sequential applications were lower than those caused by only CPF and by a mixture of CPF and F. The results indicate that sequential applications of pesticides could have a negative impact on aquatic organisms and fish yields, with implication for the aquatic biodiversity, local people's livelihood and the aquaculture industry in the Mekong Delta.

  4. CME Productivity of Active Regions.

    NASA Astrophysics Data System (ADS)

    Liu, L.; Wang, Y.; Wang, J.; Shen, C.; Ye, P.; Zhang, Q.; Liu, R.; Wang, S.

    2015-12-01

    Solar active regions (ARs) are the major sources of two kinds of the most violent solar eruptions, namely flares and coronal mass ejections (CMEs). Although they are believed to be two phenomena in the same eruptive process, the productivity of them could be quiet different for various ARs. Why is an AR productive? And why is a flare-rich AR CME-poor? To answer these questions, we compared the recent super flare-rich but CME-poor AR 12192, with other four ARs; two were productive in both flares and CMEs and the other two were inert to produce any M-class or intenser flares or CMEs. By investigating the photospheric parameters based on the SDO/HMI vector magnetogram, we find the three productive ARs have larger magnetic flux, current and free magnetic energy than the inert ARs. Furthermore, the two ARs productive in both flares and CMEs contain higher current helicity, concentrating along both sides of the flaring neutral lines, indicating the presence of a seed magnetic structure( that is highly sheared or twisted) of a CME; they also have higher decay index in the low corona, showing weak constraint. The results suggest that productive ARs are always large and have strong current system and sufficient free energy to power flares, and more importantly whether or not a flare is accompanied by a CME is seemingly related to (1) if there is significant sheared or twisted core field serving as the seed of the CME and (2) if the constraint of the overlying arcades is weak enough. Moreover, some productive ARs may frequently produce more than one CME. How does this happen? We do a statistical investigation of waiting times of quasi-homologous CMEs ( CME ssuccessive originating from the same ARs within short intervals) from super ARs in solar cycle 23 to answer this question. The waiting times of quasi-homologous CMEs have a two-component distribution with a separation at about 18 hours, the first component peaks at 7 hours. The correlation analysis among CME waiting times

  5. New Acetylcholinesterase Inhibitors for Alzheimer's Disease

    PubMed Central

    Mehta, Mona; Adem, Abdu; Sabbagh, Marwan

    2012-01-01

    Acetylcholinesterase (AChE) remains a highly viable target for the symptomatic improvement in Alzheimer's disease (AD) because cholinergic deficit is a consistent and early finding in AD. The treatment approach of inhibiting peripheral AchE for myasthenia gravis had effectively proven that AchE inhibition was a reachable therapeutic target. Subsequently tacrine, donepezil, rivastigmine, and galantamine were developed and approved for the symptomatic treatment of AD. Since then, multiple cholinesterase inhibitors (ChEI) continue to be developed. These include newer ChEIs, naturally derived ChEIs, hybrids, and synthetic analogues. In this paper, we summarize the different types of ChEIs in development and their respective mechanisms of actions. This pharmacological approach continues to be active with many promising compounds. PMID:22216416

  6. The Main Sequence of Explosive Solar Active Regions: Comparison of Emerging and Mature Active Regions

    NASA Technical Reports Server (NTRS)

    Falconer, David; Moore, Ron

    2011-01-01

    For mature active regions, an active region s magnetic flux content determines the maximum free energy the active region can have. Most Large flares and CMEs occur in active regions that are near their free-energy limit. Active-region flare power radiated in the GOES 1-8 band increases steeply as the free-energy limit is approached. We infer that the free-energy limit is set by the rate of release of an active region s free magnetic energy by flares, CMEs and coronal heating balancing the maximum rate the Sun can put free energy into the active region s magnetic field. This balance of maximum power results in explosive active regions residing in a "mainsequence" in active-region (flux content, free energy content) phase space, which sequence is analogous to the main sequence of hydrogen-burning stars in (mass, luminosity) phase space.

  7. The Twist Limit for Bipolar Active Regions

    NASA Technical Reports Server (NTRS)

    Moore, Ron; Falconer, David; Gary, Allen

    2008-01-01

    We present new evidence that further supports the standard idea that active regions are emerged magnetic-flux-rope omega loops. When the axial magnetic twist of a cylindrical flux rope exceeds a critical amount, the flux rope becomes unstable to kinking, and the excess axial twist is converted into writhe twist by the kinking. This suggests that, if active regions are emerged omega loops, then (1) no active region should have magnetic twist much above the limit set by kinking, (2) active regions having twist near the limit should often arise from kinked omega loops, and (3) since active regions having large delta sunspots are outstandingly twisted, these arise from kinked omega loops and should have twist near the limit for kinking. From each of 36 vector magnetograms of bipolar active regions, we have measured (1) the total flux of the vertical field above 100 G, (2) the area covered by this flux, and (3) the net electric current that arches over the polarity inversion line. These three quantities yield an estimate of the axial magnetic twist in a simple model cylindrical flux rope that corresponds to the top of the active region s hypothetical omega loop prior to emergence. In all 36 cases, the estimated twist is below the critical limit for kinking. The 11 most twisted active regions (1) have estimated twist within a factor of approx.3 of the limit, and (2) include all of our 6 active regions having large delta sunspots. Thus, our observed twist limit for bipolar active regions is in good accord with active regions being emerged omega loops.

  8. Dual Binding Site and Selective Acetylcholinesterase Inhibitors Derived from Integrated Pharmacophore Models and Sequential Virtual Screening

    PubMed Central

    Gupta, Shikhar; Mohan, C. Gopi

    2014-01-01

    In this study, we have employed in silico methodology combining double pharmacophore based screening, molecular docking, and ADME/T filtering to identify dual binding site acetylcholinesterase inhibitors that can preferentially inhibit acetylcholinesterase and simultaneously inhibit the butyrylcholinesterase also but in the lesser extent than acetylcholinesterase. 3D-pharmacophore models of AChE and BuChE enzyme inhibitors have been developed from xanthostigmine derivatives through HypoGen and validated using test set, Fischer's randomization technique. The best acetylcholinesterase and butyrylcholinesterase inhibitors pharmacophore hypotheses Hypo1_A and Hypo1_B, with high correlation coefficient of 0.96 and 0.94, respectively, were used as 3D query for screening the Zinc database. The screened hits were then subjected to the ADME/T and molecular docking study to prioritise the compounds. Finally, 18 compounds were identified as potential leads against AChE enzyme, showing good predicted activities and promising ADME/T properties. PMID:25050335

  9. The Effect of Parathion on Red Blood Cell Acetylcholinesterase in the Wistar Rat

    PubMed Central

    Bunya, Naofumi; Sawamoto, Keigo; Benoit, Hanif

    2016-01-01

    Organophosphorus (OP) pesticide poisoning is a significant problem worldwide. Research into new antidotes for these acetylcholinesterase inhibitors, and even optimal doses for current therapies, is hindered by a lack of standardized animal models. In this study, we sought to characterize the effects of the OP pesticide parathion on acetylcholinesterase in a Wistar rat model that included comprehensive medical care. Methods. Male Wistar rats were intubated and mechanically ventilated and then poisoned with between 20 mg/kg and 60 mg/kg of intravenous parathion. Upon developing signs of poisoning, the rats were treated with standard critical care, including atropine, pralidoxime chloride, and midazolam, for up to 48 hours. Acetylcholinesterase activity was determined serially for up to 8 days after poisoning. Results. At all doses of parathion, maximal depression of acetylcholinesterase occurred at 3 hours after poisoning. Acetylcholinesterase recovered to nearly 50% of baseline activity by day 4 in the 20 mg/kg cohort and by day 5 in the 40 and 60 mg/kg cohorts. At day 8, most rats' acetylcholinesterase had recovered to roughly 70% of baseline. These data should be useful in developing rodent models of acute OP pesticide poisoning. PMID:27418928

  10. Acetylcholinesterase of the sand fly, Phlebotomus papatasi (Scopoli): construction, expression and biochemical properties of the G119S orthologous mutant

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Phlebotomus papatasi vectors zoonotic cutaneous leishmaniasis, widespread in intertropical and temperate regions of the world. Previous cloning, expression, and biochemical characterization of recombinant P. papatasi acetylcholinesterase 1 (PpAChE1) revealed 85% amino acid sequence identity to mosq...

  11. Biochemical effects of glyphosate based herbicide, Excel Mera 71 on enzyme activities of acetylcholinesterase (AChE), lipid peroxidation (LPO), catalase (CAT), glutathione-S-transferase (GST) and protein content on teleostean fishes.

    PubMed

    Samanta, Palas; Pal, Sandipan; Mukherjee, Aloke Kumar; Ghosh, Apurba Ratan

    2014-09-01

    Effects of glyphosate based herbicide, Excel Mera 71 at a dose of 17.20mg/l on enzyme activities of acetylcholinesterase (AChE), lipid peroxidation (LPO), catalase (CAT), glutathione-S-transferase (GST) and protein content were measured in different tissues of two Indian air-breathing teleosts, Anabas testudineus (Bloch) and Heteropneustes fossilis (Bloch) during an exposure period of 30 days under laboratory condition. AChE activity was significantly increased in all the investigated tissues of both fish species and maximum elevation was observed in brain of H. fossilis, while spinal cord of A. testudineus showed minimum increment. Fishes showed significant increase LPO levels in all the tissues; highest was observed in gill of A. testudineus but lowest LPO level was observed in muscle of H. fossilis. CAT was also enhanced in both the fishes, while GST activity in liver diminished substantially and minimum was observed in liver of A. testudineus. Total protein content showed decreased value in all the tissues, maximum reduction was observed in liver and minimum in brain of A. testudineus and H. fossilis respectively. The results indicated that Excel Mera 71 caused serious alterations in the enzyme activities resulting into severe deterioration of fish health; so, AChE, LPO, CAT and GST can be used as suitable indicators of herbicidal toxicity.

  12. Depth of origin of solar active regions

    NASA Technical Reports Server (NTRS)

    Parker, E. N.

    1984-01-01

    Observations show that the individual bipolar magnetic regions on the sun remain confined during their decay phase, with much of the magnetic field pulling back under the surface, in reverse of the earlier emergence. This suggests that the magnetic field is held on a short rein by subsurface forces, for otherwise the region would decay entirely by dispersing across the face of the sun. With the simple assumption that the fields at the surface are controlled from well-defined anchor points at a depth h, it is possible to relate the length l of the bipolar region at the surface to the depth h, with h about equal to l. The observed dimensions l about equal to 100,000 km for normal active regions, and l about equal to 10,000 km for the ephemeral active regions, indicate comparable depths of origin. More detailed observational studies of the active regions may be expected to shed further light on the problem.

  13. Suppression of Active-Region CME Production by the Presence of Other Active Regions

    NASA Technical Reports Server (NTRS)

    Falconer, David; Moore, Ron; Barghouty, Abdulnasser; Khazanov, Igor

    2009-01-01

    From the SOHO mission s data base of MDI full-disk magnetograms spanning solar cycle 23, we have obtained a set of 40,000 magnetograms of 1,300 active regions, tracking each active region across the 30 degree central solar disk. Each active region magnetogram is cropped from the full-disk magnetogram by an automated code. The cadence is 96 minutes. From each active-region magnetogram, we have measured two whole-active-region magnetic quantities: (1) the magnetic size of the active region (the active region s total magnetic flux), and (2) a gauge of the active region s free magnetic energy (part of the free energy is released in the production of a flare and/or CME eruption). From NOAA Flare/CME catalogs, we have obtained the event (Flare/CME/SEP event) production history of each active region. Using all these data, we find that for each type of eruptive event, an active region s expected rate of event production increases as a power law of our gauge of active-region free magnetic energy. We have also found that, among active regions having nearly the same free energy, the rate of the CME production is less when there are many other active regions on the disk than when there are few or none, but there is no significant discernible suppression of the rate of flare production. This indicates that the presence of other active regions somehow tends to inhibit an active region s flare-producing magnetic explosions from becoming CMEs, contrary to the expectation from the breakout model for the production of CMEs.

  14. Synthesis and acetylcholinesterase/butyrylcholinesterase inhibition activity of 4-amino-2, 3-diaryl-5, 6, 7, 8-tetrahydrofuro(and thieno)[2, 3-b]-quinolines, and 4-amino-5, 6, 7, 8, 9-pentahydro-2, 3-diphenylcyclohepta[e]furo(and thieno)-[2, 3-b]pyridines.

    PubMed

    Marco, José L; De Los Ríos, Cristóbal; Carreiras, María C; Baños, Josep E; Badia, Albert; Vivas, Nuria M

    2002-07-01

    The acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibition activities of a series of 4-amino-2, 3-diaryl-5, 6, 7, 8-tetrahydrofuro[2, 3-b]quinolines (10-12)/4-amino-5, 6, 7, 8-tetrahydro-2, 3-diphenylthieno[2, 3-b]quinoline (14) and 4-amino-5, 6, 7, 8, 9-pentahydro-2, 3-diphenylcyclohepta[e]furo[2, 3-b]pyridine (13)/4-amino-5, 6, 7, 8, 9-pentahydro-2, 3-phenylcyclohepta[e]thieno[2, 3-b]pyridine (15) are described. These compounds are tacrine (THA) analogues which have been prepared either from readily available 2-amino-3-cyano-4, 5-diarylfurans (16-18) or from 2-amino-3-cyano-4, 5-diphenylthiophene (19), via Friedländer condensation with cyclohexanone or cycloheptanone. These compounds are competitive inhibitors for acetylcholinesterase, the more potent being compound (13) which is three-fold less active than tacrine. The butyrylcholinesterase inhibition activity is significant only in compounds 10 and133, which are ten-fold less active than tacrine. It is found that the products 11 and 12 strongly inhibit acetylcholinesterase, and show excellent selectivity regarding butyrylcholinesterase.

  15. Active Region Emergence and Remote Flares

    NASA Astrophysics Data System (ADS)

    Fu, Yixing; Welsch, Brian T.

    2016-02-01

    We study the effect of new emerging solar active regions on the large-scale magnetic environment of existing regions. We first present a theoretical approach to quantify the "interaction energy" between new and pre-existing regions as the difference between i) the summed magnetic energies of their individual potential fields and ii) the energy of their superposed potential fields. We expect that this interaction energy can, depending upon the relative arrangements of newly emerged and pre-existing magnetic flux, indicate the existence of "topological" free magnetic energy in the global coronal field that is independent of any "internal" free magnetic energy due to coronal electric currents flowing within the newly emerged and pre-existing flux systems. We then examine the interaction energy in two well-studied cases of flux emergence, but find that the predicted energetic perturbation is relatively small compared to energies released in large solar flares. Next, we present an observational study of the influence of the emergence of new active regions on flare statistics in pre-existing active regions, using NOAA's Solar Region Summary and GOES flare databases. As part of an effort to precisely determine the emergence time of active regions in a large event sample, we find that emergence in about half of these regions exhibits a two-stage behavior, with an initial gradual phase followed by a more rapid phase. Regarding flaring, we find that the emergence of new regions is associated with a significant increase in the occurrence rate of X- and M-class flares in pre-existing regions. This effect tends to be more significant when pre-existing and new emerging active regions are closer. Given the relative weakness of the interaction energy, this effect suggests that perturbations in the large-scale magnetic field, such as topology changes invoked in the "breakout" model of coronal mass ejections, might play a significant role in the occurrence of some flares.

  16. Hinode Captures Images of Solar Active Region

    NASA Video Gallery

    In these images, Hinode's Solar Optical Telescope (SOT) zoomed in on AR 11263 on August 4, 2011, five days before the active region produced the largest flare of this cycle, an X6.9. We show images...

  17. Musical hallucinations treated with acetylcholinesterase inhibitors.

    PubMed

    Blom, Jan Dirk; Coebergh, Jan Adriaan F; Lauw, René; Sommer, Iris E C

    2015-01-01

    Musical hallucinations are relatively rare auditory percepts which, due to their intrusive nature and the accompanying fear of impending mental decline, tend to cause significant distress and impairment. Although their etiology and pathophysiology appear to be heterogeneous and no evidence-based treatment methods are available, case reports indicate that acetylcholinesterase inhibitors may yield positive results in patients with comorbid hearing loss. We present two female patients (aged 76 and 78 years) both of whom suffered from hearing impairment and practically incessant musical hallucinations. Both patients were successfully treated with the acetylcholinesterase inhibitor rivastigmine. Based on these two case descriptions and an overview of studies describing the use of acetylcholinesterase inhibitors in similar patients, we discuss possible mechanisms and propose further research on the use of acetylcholinesterase inhibitors for musical hallucinations experienced in concordance with hearing loss.

  18. Musical Hallucinations Treated with Acetylcholinesterase Inhibitors

    PubMed Central

    Blom, Jan Dirk; Coebergh, Jan Adriaan F.; Lauw, René; Sommer, Iris E. C.

    2015-01-01

    Musical hallucinations are relatively rare auditory percepts which, due to their intrusive nature and the accompanying fear of impending mental decline, tend to cause significant distress and impairment. Although their etiology and pathophysiology appear to be heterogeneous and no evidence-based treatment methods are available, case reports indicate that acetylcholinesterase inhibitors may yield positive results in patients with comorbid hearing loss. We present two female patients (aged 76 and 78 years) both of whom suffered from hearing impairment and practically incessant musical hallucinations. Both patients were successfully treated with the acetylcholinesterase inhibitor rivastigmine. Based on these two case descriptions and an overview of studies describing the use of acetylcholinesterase inhibitors in similar patients, we discuss possible mechanisms and propose further research on the use of acetylcholinesterase inhibitors for musical hallucinations experienced in concordance with hearing loss. PMID:25904872

  19. Probing the active sites of butyrylcholinesterase and cholesterol esterase with isomalathion: conserved stereoselective inactivation of serine hydrolases structurally related to acetylcholinesterase.

    PubMed

    Doorn, J A; Talley, T T; Thompson, C M; Richardson, R J

    2001-07-01

    Previous work has shown that acetylcholinesterase (AChE), a member of the alpha/beta-hydrolase superfamily, is stereoselectively inhibited by the four stereoisomers of isomalathion. Recent kinetic and mass spectral data demonstrated that a difference in mechanism of inactivation exists for AChE treated with (1R)- versus (1S,3S)-stereoisomers. This study sought to determine whether other alpha/beta-hydrolases are stereoselectively inhibited by isomalathion and if the difference in mechanism of AChE inactivation between (1R)- and (1S,3S)-isomers is conserved for other alpha/beta-hydrolases. Bimolecular rate constants of inhibition (k(i)) were measured for human and equine butyrylcholinesterase (HBChE and EBChE, respectively) and bovine cholesterol esterase (BCholE) with all four isomers. Isomalathion isomers inhibited these enzymes with the following order of potency: (1R,3R) > (1R,3S) > (1S,3R) > or = (1S,3S). Ratios of k(i) values for the most potent to the least potent isomer were 10.5 (HBChE), 11.9 (EBChE), and 68.6 (BCholE). Rate constants of reactivation (k(3)) were measured for enzyme inhibited by isomalathion isomers. HBChE, EBChE, and BCholE inactivated by the (1R)-isomers readily reactivated. However, enzymes modified by (1S)-isomalathions were refractory toward reactivation, and k(3) values were not significantly different from zero for HBChE and BCholE treated with the (1S,3S)-isomer. Computer-based docking experiments were performed for BCholE with (1R,3R)- and (1S,3S)-enantiomers. Calculated structures predicted a difference in primary leaving group: diethyl thiosuccinate for (1R,3R)-isomalathion and thiomethyl for the (1S,3S)-isomer. The data demonstrate that the alpha/beta-hydrolases used in this study are stereoselectively inhibited by isomalathion. Furthermore, the results suggest that the mechanistic shift demonstrated to occur for inhibition of AChE by (1R)- versus (1S,3S)-isomers is conserved for butyrylcholinesterase and cholesterol esterase.

  20. Flare Size Distributions and Active Region Types

    NASA Astrophysics Data System (ADS)

    Bai, Taeil

    2007-05-01

    Size distributions of solar flares measured by various size indicators follow a power law with a negative index of about 1.8. On the basis of general appearance of power-law distributions, Lu and his collegues proposed an avalenche model. According to this model, the power-law index should be independent of active region size, but the cutoff size above which the size distribution steepens rapidly is expected to depend on the active region size. I have analyzed the size distribution of flares, using GOES soft X-ray observations for 2004 and 2005. For flares observed by GOES during these years, their locations are almost completely identified even for C-class flares. This enable us to study the dependence of size distribution on active region type. Comparing the power-law portion of size distributions below the high-end cutoff, I have found that the size distribution index depends on active region type. Flares from prolific active regions exhibit a flatter distribution, while flares from non-prolific active regions exhibit a steeper distribution. I plan to discuss a plausible mechanism for such behavior.

  1. Polar Field Reversals and Active Region Decay

    NASA Astrophysics Data System (ADS)

    Petrie, Gordon; Ettinger, Sophie

    2015-07-01

    We study the relationship between polar field reversals and decayed active region magnetic flux. Photospheric active region flux is dispersed by differential rotation and turbulent diffusion, and is transported poleward by meridional flows and diffusion. We summarize the published evidence from observation and modeling of the influence of meridional flow variations and decaying active region flux's spatial distribution, such as the Joy's law tilt angle. Using NSO Kitt Peak synoptic magnetograms covering cycles 21-24, we investigate in detail the relationship between the transport of decayed active region flux to high latitudes and changes in the polar field strength, including reversals in the magnetic polarity at the poles. By means of stack plots of low- and high-latitude slices of the synoptic magnetograms, the dispersal of flux from low to high latitudes is tracked, and the timing of this dispersal is compared to the polar field changes. In the most abrupt cases of polar field reversal, a few activity complexes (systems of active regions) are identified as the main cause. The poleward transport of large quantities of decayed trailing-polarity flux from these complexes is found to correlate well in time with the abrupt polar field changes. In each case, significant latitudinal displacements were found between the positive and negative flux centroids of the complexes, consistent with Joy's law bipole tilt with trailing-polarity flux located poleward of leading-polarity flux. The activity complexes of the cycle 21 and 22 maxima were larger and longer-lived than those of the cycle 23 and 24 maxima, and the poleward surges were stronger and more unipolar and the polar field changes larger and faster. The cycle 21 and 22 polar reversals were dominated by only a few long-lived complexes whereas the cycle 23 and 24 reversals were the cumulative effects of more numerous, shorter-lived regions. We conclude that sizes and lifetimes of activity complexes are key to

  2. Amphiphile dependency of the monomeric and dimeric forms of acetylcholinesterase from human erythrocyte membrane.

    PubMed

    Ott, P; Brodbeck, U

    1984-08-08

    Human erythrocyte membrane-bound acetylcholinesterase was converted to a monomeric species by treatment of ghosts with 2-mercaptoethanol and iodoacetic acid. After solubilization with Triton X-100, the reduced and alkylated enzyme was partially purified by affinity chromatography and separated from residual dimeric enzyme by sucrose density gradient centrifugation in a zonal rotor. Monomeric and dimeric acetylcholinesterase showed full enzymatic activity in presence of Triton X-100 whereas in the absence of detergent, activity was decreased to approx. 20% and 15%, respectively. Preformed egg phosphatidylcholine vesicles fully sustained activity of the monomeric species whereas the dimer was only 80% active. The results suggest that a dimeric structure is not required for manifestation of amphiphile dependency of membrane-bound acetylcholinesterase from human erythrocytes. Furthermore, monomeric enzyme appears to be more easily inserted into phospholipid bilayers than the dimeric species.

  3. The 17 GHz active region number

    SciTech Connect

    Selhorst, C. L.; Pacini, A. A.; Costa, J. E. R.; Giménez de Castro, C. G.; Valio, A.; Shibasaki, K.

    2014-08-01

    We report the statistics of the number of active regions (NAR) observed at 17 GHz with the Nobeyama Radioheliograph between 1992, near the maximum of cycle 22, and 2013, which also includes the maximum of cycle 24, and we compare with other activity indexes. We find that NAR minima are shorter than those of the sunspot number (SSN) and radio flux at 10.7 cm (F10.7). This shorter NAR minima could reflect the presence of active regions generated by faint magnetic fields or spotless regions, which were a considerable fraction of the counted active regions. The ratio between the solar radio indexes F10.7/NAR shows a similar reduction during the two minima analyzed, which contrasts with the increase of the ratio of both radio indexes in relation to the SSN during the minimum of cycle 23-24. These results indicate that the radio indexes are more sensitive to weaker magnetic fields than those necessary to form sunspots, of the order of 1500 G. The analysis of the monthly averages of the active region brightness temperatures shows that its long-term variation mimics the solar cycle; however, due to the gyro-resonance emission, a great number of intense spikes are observed in the maximum temperature study. The decrease in the number of these spikes is also evident during the current cycle 24, a consequence of the sunspot magnetic field weakening in the last few years.

  4. Acetylcholinesterase modulates neurite outgrowth on fibronectin.

    PubMed

    Giordano, C; Poiana, G; Augusti-Tocco, G; Biagioni, S

    2007-05-04

    Acetylcholinesterase (AChE) has been reported to be involved in the modulation of neurite outgrowth. To understand the role played by different domains, we transfected neuroblastoma cells with three constructs containing the invariant region of AChE, differing in the exon encoding the C-terminus and therefore in AChE cellular fate and localization. All isoforms increased neurite extension, suggesting the involvement of the invariant domain [A. De Jaco, G. Augusti-Tocco, S. Biagioni, Alternative AChE molecular forms exhibit similar ability to induce neurite outgrowth, J. Neurosci. Res. 70 (2002) 756-765]. The peripheral anionic site (PAS) is encoded by invariant exons and represents the domain involved in non-cholinergic functions of AChE. Masking of PAS with fasciculin results in a significant decrease of neurite outgrowth in all clones overexpressing AChE. A strong reduction was also observed when clones were cultured on fibronectin. Treatment of clones with fasciculin, therefore masking PAS, abolished the fibronectin-induced reduction. The inhibition of the catalytic site cannot revert the fibronectin effect. Finally, when clones were cultured on fibronectin in the presence of heparin, a ligand of fibronectin, the inhibitory effect was completely reversed. Our results indicate that PAS could directly or indirectly mediate AChE/fibronectin interactions.

  5. Acetylcholinesterase inhibitors and Gulf War illnesses

    PubMed Central

    Golomb, Beatrice Alexandra

    2008-01-01

    Increasing evidence suggests excess illness in Persian Gulf War veterans (GWV) can be explained in part by exposure of GWV to organophosphate and carbamate acetylcholinesterase inhibitors (AChEis), including pyridostigmine bromide (PB), pesticides, and nerve agents. Evidence germane to the relation of AChEis to illness in GWV was assessed. Many epidemiological studies reported a link between AChEi exposure and chronic symptoms in GWV. The link is buttressed by a dose–response relation of PB pill number to chronic symptoms in GWV and by a relation between avidity of AChEi clearance and illness, based on genotypes, concentrations, and activity levels of enzymes that detoxify AChEis. Triangulating evidence derives from studies linking occupational exposure to AChEis to chronic health symptoms that mirror those of ill GWV. Illness is again linked to lower activity of AChEi detoxifying enzymes and genotypes conferring less-avid AChEi detoxification. AChEi exposure satisfies Hill's presumptive criteria for causality, suggesting this exposure may be causally linked to excess health problems in GWV. PMID:18332428

  6. Esterase detoxification of acetylcholinesterase inhibitors by ...

    EPA Pesticide Factsheets

    Organophosphate (OP) and N-methylcarbamate pesticides inhibit acetylcholinesterase (AChE), but differences in metabolism and detoxification can influence potency of these pesticides across and within species. Carboxylesterase (CaE) and A-esterase (paraoxonase, PON) are considered factors underlying age-related sensitivity differences. We used an in vitro system to measure detoxification of AChE-inhibiting pesticides mediated via these esterases. Recombinant human AChE was used as a bioassay of inhibitor concentration following incubation with detoxifying tissue: liver plus Ca+2 (to stimulate PONs, measuring activity of both esterases) or EGTA (to inhibit PONs, thereby measuring CaE activity). Inhibitory concentrations of aldicarb, chlorpyrifos oxon, malaoxon, methamidophos, oxamyl, paraoxon, and methyl paraoxon were incubated with liver from adult male rat or one of 20 commercially provided human (11-83 years of age) liver samples. Detoxification was the difference in inhibition produced by the pesticide alone or in combination with liver plus Ca+2 or EGTA. Generally, rat liver produced more detoxification than did the human samples. There were large detoxification differences, which were not correlated with age or sex, across human samples for some pesticides (especially malaoxon, chlorpyrifos oxon) but not for others (e.g., aldicarb, methamidophos). Chlorpyrifos oxon was detoxified only in the presence of Ca+2 in both rat and human livers. Detoxification of pa

  7. Fluxon Modeling of Active Region Evolution

    NASA Astrophysics Data System (ADS)

    Deforest, C. E.; Kankelborg, C. C.; Davey, A. R.; Rachmeler, L.

    2006-12-01

    We present current results and status on fluxon modeling of free energy buildup and release in active regions. Our publicly available code, FLUX, has the unique ability to track magnetic energy buildup with a truly constrained topology in evolving, nonlinear force-free conditions. Recent work includes validation of the model against Low &Lou force-free field solutions, initial evolution studies of idealized active regions, and inclusion of locally parameterized reconnection into the model. FLUX is uniquely able to simulate complete active regions in 3-D on a single workstation; we estimate that a parallelized fluxon model, together with computer vision code to ingest solar data, could run faster than real time on a cluster of \\textasciitilde 30 CPUs and hence provide a true predictive space weather model in the style of predictive simulations of terrestrial weather.

  8. The Magnetic Free Energy in Active Regions

    NASA Technical Reports Server (NTRS)

    Metcalf, Thomas R.; Mickey, Donald L.; LaBonte, Barry J.

    2001-01-01

    The magnetic field permeating the solar atmosphere governs much of the structure, morphology, brightness, and dynamics observed on the Sun. The magnetic field, especially in active regions, is thought to provide the power for energetic events in the solar corona, such as solar flares and Coronal Mass Ejections (CME) and is believed to energize the hot coronal plasma seen in extreme ultraviolet or X-rays. The question remains what specific aspect of the magnetic flux governs the observed variability. To directly understand the role of the magnetic field in energizing the solar corona, it is necessary to measure the free magnetic energy available in active regions. The grant now expiring has demonstrated a new and valuable technique for observing the magnetic free energy in active regions as a function of time.

  9. Distribution of sup 125 I-neurotensin binding sites in human forebrain: Comparison with the localization of acetylcholinesterase

    SciTech Connect

    Szigethy, E.; Quirion, R.; Beaudet, A. )

    1990-07-22

    The distribution of 125I-neurotensin binding sites was compared with that of acetylcholinesterase reactivity in the human basal forebrain by using combined light microscopic radioautography/histochemistry. High 125I-neurotensin binding densities were observed in the bed nucleus of the stria terminalis, islands of Calleja, claustrum, olfactory tubercle, and central nucleus of the amygdala; lower levels were seen in the caudate, putamen, medial septum, diagonal band nucleus, and nucleus basalis of Meynert. Adjacent sections processed for cholinesterase histochemistry demonstrated a regional overlap between the distribution of labeled neurotensin binding sites and that of intense acetylcholinesterase staining in all of the above regions, except in the bed nucleus of the stria terminalis, claustrum, and central amygdaloid nucleus, where dense 125I-neurotensin labeling was detected over areas containing only weak to moderate cholinesterase staining. At higher magnification, 125I-neurotensin-labeled binding sites in the islands of Calleja, supraoptic nucleus of the hypothalamus, medial septum, diagonal band nucleus, and nucleus basalis of Meynert were selectively associated with neuronal perikarya found to be cholinesterase-positive in adjacent sections. Moderate 125I-neurotensin binding was also apparent over the cholinesterase-reactive neuropil of these latter three regions. These data suggest that neurotensin (NT) may directly influence the activity of magnocellular cholinergic neurons in the human basal forebrain, and may be involved in the physiopathology of dementing disorders such as Alzheimer's disease, in which these neurons have been shown to be affected.

  10. Active Region Segmentation Based on Stokes Asymmetries

    NASA Astrophysics Data System (ADS)

    Choi, Jieun; Harker-Lundberg, B.

    2011-01-01

    During the Stokes inversion process, we would ideally use a distinct model for each structure in an active region which addresses the differences in the physical conditions of these regions. While the Milne-Eddington model of the atmosphere---a frequently-used ideal model that assumes all local thermodynamic equilibrium (LTE) conditions are satisfied---is a sufficient approximation for the description of the solar photosphere, we almost always observe deviations from this model. It is thus of interest to devise a method to systematically and accurately identify the active regions based on their spectra, such that we could use a more sophisticated model catered to each structure in an active region during the actual Stokes inversion process. We present a classification scheme for different active region structures using Stokes asymmetries and line core depths as discriminators. The data used for this investigation were obtained from the Synoptic Optical Long-term Investigations of the Sun (SOLIS) facility using the Vector Spectromagnetograph (VSM), observed in a 3 A bandpass around Fe I 6302.5 A, from March 27, 2008 to March 29, 2008. This work is carried out through the National Solar Observatory Research Experiences for Undergraduate (REU) site program, which is co-funded by the Department of Defense in partnership with the National Science Foundation REU Program. The National Solar Observatory is operated by the Association of Universities for Research in Astronomy, Inc. (AURA) under cooperative agreement with the National Science Foundation.

  11. ON THE FORMATION OF ACTIVE REGIONS

    SciTech Connect

    Stein, Robert F.; Nordlund, Ake E-mail: aake@nbi.dk

    2012-07-01

    Magnetoconvection can produce an active region without an initial coherent flux tube. A simulation was performed where a uniform, untwisted, horizontal magnetic field of 1 kG strength was advected into the bottom of a computational domain 48 Mm wide by 20 Mm deep. The up and down convective motions produce a hierarchy of magnetic loops with a wide range of scales, with smaller loops riding 'piggy-back' in a serpentine fashion on larger loops. When a large loop approaches the surface, it produces a small active region with a compact leading spot and more diffuse following spots.

  12. Polar Field Reversals and Active Region Decay

    NASA Astrophysics Data System (ADS)

    Petrie, Gordon; Ettinger, Sophie

    2015-04-01

    We study the relationship between polar field reversals and decayed active region magnetic flux. Photospheric active region flux is dispersed by differential rotation and turbulent diffusion, and is transported poleward by meridional flows and diffusion. Using NSO Kitt Peak synoptic magnetograms, we investigate in detail the relationship between the transport of decayed active region flux to high latitudes and changes in the polar field strength, including reversals in the magnetic polarity at the poles. By means of stack plots of low- and high-latitude slices of the synoptic magnetograms, the dispersal of flux from low to high latitudes is tracked, and the timing of this dispersal is compared to the polar field changes. In the most abrupt cases of polar field reversal, a few activity complexes (systems of active regions) are identified as the main cause. The poleward transport of large quantities of decayed lagging-polarity flux from these complexes is found to correlate well in time with the abrupt polar field changes. In each case, significant latitudinal displacements were found between the positive and negative flux centroids of the complexes, consistent with Joy's law bipole tilt with lagging-polarity flux located poleward of leading-polarity flux. This work is carried out through the National Solar Observatory Summer Research Assistantship (SRA) Program. The National Solar Observatory is operated by the Association of Universities for Research in Astronomy, Inc. (AURA) under cooperative agreement with the National Science Foundation.

  13. Modulation of the Immune Response by Nematode Secreted Acetylcholinesterase Revealed by Heterologous Expression in Trypanosoma musculi

    PubMed Central

    Vaux, Rachel; Schnoeller, Corinna; Berkachy, Rita; Roberts, Luke B.; Hagen, Jana; Gounaris, Kleoniki

    2016-01-01

    Nematode parasites secrete molecules which regulate the mammalian immune system, but their genetic intractability is a major impediment to identifying and characterising the biological effects of these molecules. We describe here a novel system for heterologous expression of helminth secreted proteins in the natural parasite of mice, Trypanosoma musculi, which can be used to analyse putative immunomodulatory functions. Trypanosomes were engineered to express a secreted acetylcholinesterase from Nippostrongylus brasiliensis. Infection of mice with transgenic parasites expressing acetylcholinesterase resulted in truncated infection, with trypanosomes cleared early from the circulation. Analysis of cellular phenotypes indicated that exposure to acetylcholinesterase in vivo promoted classical activation of macrophages (M1), with elevated production of nitric oxide and lowered arginase activity. This most likely occurred due to the altered cytokine environment, as splenocytes from mice infected with T. musculi expressing acetylcholinesterase showed enhanced production of IFNγ and TNFα, with diminished IL-4, IL-13 and IL-5. These results suggest that one of the functions of nematode secreted acetylcholinesterase may be to alter the cytokine environment in order to inhibit development of M2 macrophages which are deleterious to parasite survival. Transgenic T. musculi represents a valuable new vehicle to screen for novel immunoregulatory proteins by extracellular delivery in vivo to the murine host. PMID:27802350

  14. Evidence for non-acetylcholinesterase mechanisms in ...

    EPA Pesticide Factsheets

    Acetylcholinesterase inhibition is a well-established mode of action for adverse effects of organophosphorus and carbamate pesticides, and the use of this endpoint in regulatory considerations has been assumed to be protective of downstream cholinergic effects. It has been questioned whether neurodevelopmental outcomes are also a consequence of this enzyme inhibition, or whether there are alternative non-cholinesterase mechanisms by which these chemicals alter key events in nervous system development. There is a growing body of literature in laboratory animals indicating that gestational and/or postnatal exposure may cause persistent behavioral effects into adulthood, as well as emerging epidemiological reports of neurodevelopmental outcomes in children. Common experimental findings are alterations in motor activity, cognitive function, and affective and social behaviors in rats or mice, as well as disrupted neuromotor and cognitive development in children. However, the data do not provide evidence for a characteristic pattern of effects. This may suggest nonspecific alterations in neurobehavioral function, but it may also be the result of considerable differences in exposure parameters, experimental designs, test methods and equipment, populations and animal models, and a host of other variables. A number of pesticides have been implicated, but the database for chlorpyrifos is the largest and thus those studies influence any evaluations of trend. Specific attri

  15. Silicon on insulator with active buried regions

    DOEpatents

    McCarthy, Anthony M.

    1996-01-01

    A method for forming patterned buried components, such as collectors, sources and drains, in silicon-on-insulator (SOI) devices. The method is carried out by epitaxially growing a suitable sequence of single or multiple etch stop layers ending with a thin silicon layer on a silicon substrate, masking the silicon such that the desired pattern is exposed, introducing dopant and activating in the thin silicon layer to form doped regions. Then, bonding the silicon layer to an insulator substrate, and removing the silicon substrate. The method additionally involves forming electrical contact regions in the thin silicon layer for the buried collectors.

  16. Silicon on insulator with active buried regions

    DOEpatents

    McCarthy, A.M.

    1998-06-02

    A method is disclosed for forming patterned buried components, such as collectors, sources and drains, in silicon-on-insulator (SOI) devices. The method is carried out by epitaxially growing a suitable sequence of single or multiple etch stop layers ending with a thin silicon layer on a silicon substrate, masking the silicon such that the desired pattern is exposed, introducing dopant and activating in the thin silicon layer to form doped regions. Then, bonding the silicon layer to an insulator substrate, and removing the silicon substrate. The method additionally involves forming electrical contact regions in the thin silicon layer for the buried collectors. 10 figs.

  17. Silicon on insulator with active buried regions

    DOEpatents

    McCarthy, A.M.

    1996-01-30

    A method is disclosed for forming patterned buried components, such as collectors, sources and drains, in silicon-on-insulator (SOI) devices. The method is carried out by epitaxially growing a suitable sequence of single or multiple etch stop layers ending with a thin silicon layer on a silicon substrate, masking the silicon such that the desired pattern is exposed, introducing dopant and activating in the thin silicon layer to form doped regions. Then, bonding the silicon layer to an insulator substrate, and removing the silicon substrate. The method additionally involves forming electrical contact regions in the thin silicon layer for the buried collectors. 10 figs.

  18. Silicon on insulator with active buried regions

    DOEpatents

    McCarthy, Anthony M.

    1998-06-02

    A method for forming patterned buried components, such as collectors, sources and drains, in silicon-on-insulator (SOI) devices. The method is carried out by epitaxially growing a suitable sequence of single or multiple etch stop layers ending with a thin silicon layer on a silicon substrate, masking the silicon such that the desired pattern is exposed, introducing dopant and activating in the thin silicon layer to form doped regions. Then, bonding the silicon layer to an insulator substrate, and removing the silicon substrate. The method additionally involves forming electrical contact regions in the thin silicon layer for the buried collectors.

  19. Magnetic helicity in emerging solar active regions

    SciTech Connect

    Liu, Y.; Hoeksema, J. T.; Bobra, M.; Hayashi, K.; Sun, X.; Schuck, P. W.

    2014-04-10

    Using vector magnetic field data from the Helioseismic and Magnetic Imager instrument aboard the Solar Dynamics Observatory, we study magnetic helicity injection into the corona in emerging active regions (ARs) and examine the hemispheric helicity rule. In every region studied, photospheric shearing motion contributes most of the helicity accumulated in the corona. In a sample of 28 emerging ARs, 17 follow the hemisphere rule (61% ± 18% at a 95% confidence interval). Magnetic helicity and twist in 25 ARs (89% ± 11%) have the same sign. The maximum magnetic twist, which depends on the size of an AR, is inferred in a sample of 23 emerging ARs with a bipolar magnetic field configuration.

  20. Supergranule Diffusion and Active Region Decay

    NASA Technical Reports Server (NTRS)

    Hathaway, David H.; Choudhary, Debi Prasad

    2004-01-01

    Models of the Sun's magnetic dynamo include turbulent diffusion to parameterize the effects of convective motions on the evolution of the Sun's magnetic field. Supergranules are known to dominate the evolution of the surface magnetic field structure as evidenced by the structure of both the active and quiet magnetic network. However, estimates for the dif hivity attributed to su perymules differ by an order of magnitude from about 100 km sup2/s to more than 1000 km sup2/s. We examine this question of the e i v i t y using three merent approaches. 1) We study the decay of more than 30,000 active regions by determining the rate of change in the sunspot area of each active region from day-to-day. 2) We study the decay of a single isolated active region near the time of solar minimum by examining the magnetic field evolution over five solar rotations fiom SOHOMDI magnetograms obtained at 96-minute intervals. 3) We study the characteristics of supergranules that influence the estimates of their diffusive properties - flow speeds and lifetimes as functions of size - fiom SOHO/MDI Dopplergrams.

  1. Beyond Acetylcholinesterase Inhibitors: Novel Cholinergic Treatments for Alzheimer's Disease.

    PubMed

    Kamkwalala, Asante R; Newhouse, Paul A

    2017-01-01

    The major components of the cholinergic receptor system of the human brain include projections from the basal forebrain nuclei, and utilize the two types of receptors that they synapse on, nicotinic and muscarinic acetylcholine receptors. With the widespread cortical and subcortical projections of the basal forebrain, activity of these two receptor systems provide modulation of neurotransmitter activity underlying normal cognitive processes, such as attention, episodic memory, and working memory. Alzheimer's disease (AD) targets and damages cholinergic neurons in the basal forebrain, and as these projections are lost, cognitive performance progressively declines. Currently, the most widely prescribed treatment for AD is acetylcholinesterase inhibitor medications, which work by partially blocking the degradation of acetylcholine in the synapse and enabling more of the neurotransmitter to reach and activate cholinergic receptors. However since these medications have limited effectiveness, alternate treatments that focus on augmenting the activity of the receptors themselves, independent of acetylcholinesterase inhibition, are being explored. This review will discuss: 1) the role of the cholinergic system in modulating cognition, 2) novel cholinergic treatment strategies for AD-related cognitive decline, in particular treatments intended to increase cholinergic system activity by selectively targeting muscarinic and nicotinic acetylcholinergic receptors to improve cognitive performance, 3) risks, and additional considerations for cholinergic cognitive treatments for AD.

  2. Patterns of helicity in solar active regions

    NASA Technical Reports Server (NTRS)

    Pevtsov, Alexei A.; Canfield, Richard C.; Metcalf, Thomas R.

    1994-01-01

    Using 46 vector magnetograms from the Stokes Polarimeter of Mees Solar Observatory (MSO), we studied patterns of local helicity in three diverse solar active regions. From these magnetograms we computed maps of the local helicity parameter alpha = J(sub z)/B(sub z). Although such maps are noisy, we found patterns at the level approximately 2 to 3 sigma(sub J(sub z)), which repeat in successive magnetograms for up to several days. Typically, the alpha maps of any given active region contain identifiable patches with both positive and negative values of alpha. Even within a single sunspot complex, several such alpha patches can often be seen. We followed 68 alpha patches that could be identified on at least two successive alpha maps. We found that the persistence fraction of such patches decrease exponentially, with a characteristic time approximately 27 hr.

  3. Anti-Acetylcholinesterase Alkaloids from Annona glabra Leaf.

    PubMed

    Lee, Shoei-Sheng; Wu, Dong-Yi; Tsai, Sheng-Fa; Chen, Chien-Kuang

    2015-06-01

    Bioassay guided fractionation and separation of the EtOH extract of Annona glabra leaf against acetylcholinesterse led to the characterization of 15 alkaloids. Among them, (-)-actinodaphnine (2) and (-)-(6aS,7R)-7-hydroxyactinodaphnine (9) are new aporphines, although (+)-2 and (±)-2 have been found in several plants. Their structures were established by spectroscopic analysis. (-)-Anolobine (5) and (-)-roemeroline (8) showed moderate inhibitory activity against eel acetylcholinesterase with IC50 values of 22.4 and 26.3 μM, respectively.

  4. Computer Image Analysis of Histochemically-Labeled Acetylcholinesterase.

    DTIC Science & Technology

    1984-11-30

    image analysis on conjunction with histochemical techniques to describe the distribution of acetylcholinesterase (AChE) activity in nervous and muscular tissue in rats treated with organophosphates (OPs). The objective of the first year of work on this remaining 2 years. We began by adopting a version of the AChE staining method as modified by Hanker, which consistent with the optical properties of our video system. We wrote computer programs for provide a numeric quantity which represents the degree of staining in a tissue section. The staining was calibrated by

  5. Immobilization of Acetylcholinesterase on Screen-Printed Electrodes. Application to the Determination of Arsenic(III)

    PubMed Central

    Sanllorente-Méndez, Silvia; Domínguez-Renedo, Olga; Arcos-Martínez, M. Julia

    2010-01-01

    Enzymatic amperometric procedures for measuring arsenic, based on the inhibitive action of this metal on acetylcholinesterase enzyme activity, have been developed. Screen-printed carbon electrodes (SPCEs) were used with acetylcholinesterase covalently bonded directly to its surface. The amperometric response of acetylcholinesterase was affected by the presence of arsenic ions, which caused a decrease in the current intensity. The experimental optimum working conditions of pH, substrate concentration and potential applied, were established. Under these conditions, repeatability and reproducibility of biosensors were determined, reaching values below 4% in terms of relative standard deviation. The detection limit obtained for arsenic was 1.1 × 10−8 M for Ach/SPCE biosensor. Analysis of the possible effect of the presence of foreign ions in the solution was performed. The method was applied to determine levels of arsenic in spiked tap water samples. PMID:22294918

  6. Age-related learning and memory deficits in rats: role of altered brain neurotransmitters, acetylcholinesterase activity and changes in antioxidant defense system.

    PubMed

    Haider, Saida; Saleem, Sadia; Perveen, Tahira; Tabassum, Saiqa; Batool, Zehra; Sadir, Sadia; Liaquat, Laraib; Madiha, Syeda

    2014-06-01

    Oxidative stress from generation of increased reactive oxygen species or free radicals of oxygen has been reported to play an important role in the aging. To investigate the relationship between the oxidative stress and memory decline during aging, we have determined the level of lipid peroxidation, activities of antioxidant enzymes, and activity of acetylcholine esterase (AChE) in brain and plasma as well as biogenic amine levels in brain from Albino-Wistar rats at age of 4 and 24 months. The results showed that the level of lipid peroxidation in the brain and plasma was significantly higher in older than that in the young rats. The activities of antioxidant enzymes displayed an age-dependent decline in both brain and plasma. Glutathione peroxidase and catalase activities were found to be significantly decreased in brain and plasma of aged rats. Superoxide dismutase (SOD) was also significantly decreased in plasma of aged rats; however, a decreased tendency (non-significant) of SOD in brain was also observed. AChE activity in brain and plasma was significantly decreased in aged rats. Learning and memory of rats in the present study was assessed by Morris Water Maze (MWM) and Elevated plus Maze (EPM) test. Short-term memory and long-term memory was impaired significantly in older rats, which was evident by a significant increase in the latency time in MWM and increase in transfer latency in EPM. Moreover, a marked decrease in biogenic amines (NA, DA, and 5-HT) was also found in the brain of aged rats. In conclusion, our data suggest that increased oxidative stress, decline of antioxidant enzyme activities, altered AChE activity, and decreased biogenic amines level in the brain of aged rats may potentially be involved in diminished memory function.

  7. Effect of Salvia miltiorrhiza root extract on brain acetylcholinesterase and butyrylcholinesterase activities, their mRNA levels and memory evaluation in rats.

    PubMed

    Ozarowski, Marcin; Mikolajczak, Przemyslaw L; Piasecka, Anna; Kujawski, Radoslaw; Bartkowiak-Wieczorek, Joanna; Bogacz, Anna; Szulc, Michal; Kaminska, Ewa; Kujawska, Malgorzata; Gryszczynska, Agnieszka; Kachlicki, Piotr; Buchwald, Waldemar; Klejewski, Andrzej; Seremak-Mrozikiewicz, Agnieszka

    2017-05-01

    Salvia miltiorrhiza (Lamiaceae), one of the most important and popular plants of traditional medicine of Asia, is used for the prevention and treatment of cardiovascular diseases and in central nervous system disturbances. The main aim of this study was to assess the influence of subchronic (28-fold) administration of Salvia miltiorrhiza root extract (SE, 200mg/kg, p.o.) on behavioural activity and memory of rats and to evaluate the activities of cholinesterases (AChE and BuChE) and gene expression levels of AChE and BuChE as well as of beta-secretase (BACE1) in the hippocampus and frontal cortex in vivo. Huperzine A (HU, 0.5mg/kg b.w., p.o.) served as a positive control substance, whereas scopolamine (0.5mg/kg, i.p.) injection was used as a well-known model of memory impairment. The results showed that subchronic administration of SE led to an improvement of long-term memory of rats. Strong inhibition of AChE and BuChE mRNA transcription in the frontal cortex of rats treated with SE or HU was observed. The BACE1 transcript level was significantly decreased. AChE activity was statistically significantly inhibited in the frontal cortex and the hippocampus by SE (47% and 55%, respectively). Similar effects were observed in the case of HU. In summary, activity of SE provides evidence that the plant can be a source of drugs used in the treatment of Alzheimer disease.

  8. Solar irradiance variations due to active regions

    SciTech Connect

    Oster, L.; Schatten, K.H.; Sofia, S.

    1982-05-15

    We have been able to reproduce the variations of the solar irradiance observed by ACRIM to an accuracy of better than +- 0.4 W m/sup -2/, assuming that during the 6 month observation period in 1980 the solar luminosity was constant. The improvement over previous attempts is primarily due to the inclusion of faculae. The reproduction scheme uses simple geometrical data on spot and facula areas, and conventional parameters for the respective fluxes and angular dependencies. The quality of reproduction is not very sensitive to most of the details of these parameters; nevertheless, there conventional parameters cannot be very different from their actual values in the solar atmosphere. It is interesting that the time average of the integrated excess emission (over directions) of the faculae cancels out the integrated deficit produced by the spots, within an accuracy of about 10%. If this behavior were maintained over longer periods of time, say, on the order of an activity cycle, active regions could be viewed as a kind of lighthouse where the energy deficit near the normal direction, associated with the spots, is primarily reemitted close to the tangential directions by the faculae. The currently available data suggest that energy ''storage'' associated with the redirection of flux near active regions on the Sun is comparable to the lifetime of the faculae.

  9. The evolution of active region loop plasma

    NASA Technical Reports Server (NTRS)

    Krall, K. R.; Antiochos, S. K.

    1980-01-01

    The adjustment of coronal active-region loops to changes in their heating rate is investigated numerically. The one-dimensional hydrodynamic equations are solved subject to boundary conditions in which heat flux-induced mass exchange between coronal and chromospheric components is allowed. The calculated evolution of physical parameters suggests that (1) mass supplied during chromospheric evaporation is much more effective in moderating coronal temperature excursions than when downward heat flux is dissipated by a static chromosphere, and (2) the method by which the chromosphere responds to changing coronal conditions can significantly influence coronal readjustment time scales. Observations are cited which illustrate the range of possible fluctuations in the heating rates.

  10. Acetylcholinesterase of Haematobia irritans (Diptera: Muscidae): Baculovirus expression, biochemical properties and organophosphate insensitivity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This study reports the baculovirus expression and biochemical characterization of recombinant acetylcholinesterase from Haematobia irritans (L) (rHiAChE) and the effect of the previously described G262A mutation on enzyme activity and sensitivity to selected organophosphates. The rHiAChE was confirm...

  11. Brain acetylcholinesterase diurnal variations during the rapid development of tolerance to the hypothermic effect of ethanol

    SciTech Connect

    Wang, O.; Soliman, K.F.A. )

    1991-03-11

    Male Sprague-Dawley rats maintained under controlled environmental conditions were used. Acetylcholinesterase (AChE) activity was determined in the cerebral cortex, midbrain, hypothalamus, hippocampus, cerebellum, pons and medulla oblongata of saline control and ethanol-treated rats, either after a single dose at 06:0 or 18:00h, or after a second dose administered 24 hrs later at the same time scheduled. Results of this experiment indicate that repeated administration with ethanol was associated with the rapid development of tolerance to the hypothermic action of ethanol. A single injection of ethanol at 0600h resulted in a significant decrease in AChE activity in the hypothalamus, medulla, cerebellum, hippocampus and the cortex. However, ethanol administration at 18.00h was associated with significant increases in AChE activity in the same brain regions. The repeated administration of ethanol at 06.00h was associated with tolerance in AChE response to ethanol in the hypothalamus and hippocampus. However, there was no tolerance development in AChE activity in brain regions when ethanol was administered at 18.00h. The results indicate that chronotolerance to ethanol might be related to the brain cholinergic system.

  12. Use of a novel radiometric method to assess the inhibitory effect of donepezil on acetylcholinesterase activity in minimally diluted tissue samples

    PubMed Central

    Kikuchi, Tatsuya; Okamura, Toshimitsu; Arai, Takuya; Obata, Takayuki; Fukushi, Kiyoshi; Irie, Toshiaki; Shiraishi, Tetsuya

    2010-01-01

    Background and purpose: Cholinesterase inhibitors have been widely used for the treatment of patients with dementia. Monitoring of the cholinesterase activity in the blood is used as an indicator of the effect of the cholinesterase inhibitors in the brain. The selective measurement of cholinesterase with low tissue dilution is preferred for accurate monitoring; however, the methods have not been established. Here, we investigated the effect of tissue dilution on the action of cholinesterase inhibitors using a novel radiometric method with selective substrates, N-[14C]methylpiperidin-4-yl acetate ([14C]MP4A) and (R)-N-[14C]methylpiperidin-3-yl butyrate ([14C]MP3B_R), for AChE and butyrylcholinesterase (BChE) respectively. Experimental approach: We investigated the kinetics of hydrolysis of [14C]-MP4A and [14C]-MP3B_R by cholinesterases, and evaluated the selectivity of [14C]MP4A and [14C]MP3B_R for human AChE and BChE, respectively, compared with traditional substrates. Then, IC50 values of cholinesterase inhibitors in minimally diluted and highly diluted tissues were measured with [14C]MP4A and [14C]MP3B_R. Key results: AChE and BChE activities were selectively measured as the first-order hydrolysis rates of [14C]-MP4A and [14C]MP3B_R respectively. The AChE selectivity of [14C]MP4A was an order of magnitude higher than traditional substrates used for the AChE assay. The IC50 values of specific AChE and BChE inhibitors, donepezil and ethopropazine, in 1.2-fold diluted human whole blood were much higher than those in 120-fold diluted blood. In addition, the IC50 values of donepezil in monkey brain were dramatically decreased as the tissue was diluted. Conclusions and implications: This method would effectively monitor the activity of cholinesterase inhibitors used for therapeutics, pesticides and chemical warfare agents. PMID:20401964

  13. Pd(II) complexes of acetylcholinesterase reactivator obidoxime

    PubMed Central

    Stoykova, Silviya; Atanasov, Vasil; Pantcheva, Ivayla; Antonov, Liudmil

    2014-01-01

    The ability of the acetylcholinesterase reactivator obidoxime (H2L2+) to bind palladium(II) cations was evaluated spectrophotometrically at different reaction conditions (pH, reaction time, metal-to-ligand molar ratio). The results showed that immediately after mixing the reagents, pH 7.4, complex species of composition [PdHL]3+ existed predominantly with a value of conditional stability constant lgβ‘=6.52. The reaction was completed within 24 hours affording the formation of species [Pd2L]4+ with significantly increased stability (lgβ‘=9.34). The spectral data suggest that obidoxime coordinates metal(II) ions through the oximate functional groups. The in vitro reactivation assay of paraoxon-inhibited rat brain acetylcholinesterase revealed that the new complex species were much less active than the non-coordinated obidoxime. The lack of reactivation ability could be explained by the considerable stability of complexes in solution as well as by the deprotonation of oxime groups essential for recovery of the enzymatic activity. PMID:26109891

  14. Pederson Current Dissipation In Emerging Active Regions

    NASA Astrophysics Data System (ADS)

    Leake, James E.; Linton, M. G.

    2011-05-01

    Pederson current dissipation in emerging active regions. Certain regions of the solar atmosphere, such as the photosphere and chromosphere, as well as prominences, contain a significant amount of neutral atoms, and a complete description of the plasma requires including the effects of partial ionization. In the chromosphere the dissipation of Pederson currents is important for the evolution of emerging magnetic fields. Due to the relatively high number density in the chromosphere, the ion-neutral collision time-scale is much smaller than timescales associated with flux emergence. Hence we use a single-fluid approach to model the partially ionized plasma. Looking at both the emergence of large-scale sub-surface structures, and the emergence and reconnection of undulatory fields, we investigate the effect of Pederson current dissipation on the state of the emerging field, on magnetic reconnection and on dissipative heating of the atmosphere. Specifically we examine the effect of motions across fieldlines in the partially ionized regions, and how this can increase the free energy supplied to the corona by flux emergence. We also look at reconnection associated with flux emergence in the partially ionized atmosphere, and how this can account for observed small-scale brightenings (Ellerman Bombs).

  15. HEROES Observations of a Quiescent Active Region

    NASA Astrophysics Data System (ADS)

    Shih, A. Y.; Christe, S.; Gaskin, J.; Wilson-Hodge, C.

    2014-12-01

    Hard X-ray (HXR) observations of solar flares reveal the signatures of energetic electrons, and HXR images with high dynamic range and high sensitivity can distinguish between where electrons are accelerated and where they stop. Even in the non-flaring corona, high-sensitivity HXR measurements may be able to detect the presence of electron acceleration. The High Energy Replicated Optics to Explore the Sun (HEROES) balloon mission added the capability of solar observations to an existing astrophysics balloon payload, HERO, which used grazing-incidence optics for direct HXR imaging. HEROES measures HXR emission from ~20 to ~75 keV with an angular resolution of 33" HPD. HEROES launched on 2013 September 21 from Fort Sumner, New Mexico, and had a successful one-day flight. We present the detailed analysis of the 7-hour observation of AR 11850, which sets new upper limits on the HXR emission from a quiescent active region, with corresponding constraints on the numbers of tens of keV energetic electrons present. Using the imaging capability of HEROES, HXR upper limits are also obtained for the quiet Sun surrounding the active region. We also discuss what can be achieved with new and improved HXR instrumentation on balloons.

  16. Inhibition of acetylcholinesterase in guppies (Poecilia reticulata) by chlorpyrifos at sublethal concentrations: Methodological aspects

    SciTech Connect

    van der Wel, H.; Welling, W.

    1989-04-01

    Acetylcholinesterase activity is a potential biochemical indicator of toxic stress in fish and a sensitive parameter for testing water for the presence of organophosphates. A number of methodological aspects regarding the determination of the in vivo effect of chlorpyrifos on acetylcholinesterase in guppies have been investigated. It was found that with acetylthiocholine as a substrate, the contribution of pseudocholinesterase to the total cholinesterase activity can be neglected. Protection of acetylcholinesterase of guppies exposed to chlorpyrifos from additional, artifactual in vitro enzyme inhibition during homogenization is necessary. Very low concentrations of acetone in the exposure medium, resulting from dilution of the stock solution of chlorpyrifos in acetone, can result in large decreases in the oxygen content of this medium. This may affect the uptake rate of the toxic compound and, thereby, cholinesterase inhibition. Very low, sublethal concentrations of chlorpyrifos result in high inhibition levels of acetylcholinesterase (80-90%) in guppies within 2 weeks of continuous exposure. Recovery of the enzyme activity occurs after the exposed animals are kept in clean medium for 4 days, but the rate of recovery is considerably lower than the rate of inhibition.

  17. Active region coronal loops - Structural and variability

    NASA Technical Reports Server (NTRS)

    Haisch, Bernhard M.; Strong, Keith T.; Harrison, Richard A.; Gary, G. A.

    1988-01-01

    X-ray images of a pair of active region loops are studied which show significant, short time-scale variability in the line fluxes of O VIII, Ne IX, and Mg XI and in the 3.5-11.5 keV soft X-ray bands. Vector magnetograms and high-resolution UV images were used to model the three-dimensional characteristics of the loops. X-ray light curves were generated spanning four consecutive orbits for both loops individually, and light curves of the loop tops and brightest points were also generated. The largest variations involve flux changes of up to several hundred percent on time scales of 10 minutes. No significant H-alpha flare activity is reported, and loop temperatures remain in the four to six million K range. The decay phases of the light curves indicate radiative cooling, inhibition of conduction, and some type of 'continued heating' due to ongoing, underlying activity at the microflare level.

  18. Active Region Transient Brightenings : EIT Versus SXT

    NASA Astrophysics Data System (ADS)

    Berghmans, D.; McKenzie, D.; Clette, F.

    1999-10-01

    On May 13, 1998, the Extreme-Ultraviolet Imaging Telescope (EIT, on board SOHO) has produced a unique image sequence operating in 'shutterless mode' (SOHO JOP 80). In JOP 80, EIT is the leading instrument, followed by several space born instruments (SXT, TRACE, MDI, CDS, SUMER), as well as two observatories on the ground (in La Palma and Sac Peak). The target of the campaign was a relatively small but rapidly evolving active region (AR 8218). For the EIT contribution, a 15 s cadence was achieved in the Fe XII bandpass at 195 deg by leaving EIT's shutter open for 1 hour and operating the CCD in frame transfer mode. We have started the analysis of the huge data set, by making an inventory of the transients observed in the EIT image sequence. These transients range from a B3.5 flare producing a large plasma flow along pre-existing loops, to smaller EUV brightenings of active region loops. In addition, a new class of weaker footpoint brightenings was discovered that produce wave-like disturbances propagating along quasi-open field lines (see the presentation by Eva Robbrecht at this workshop). In this paper we take the opportunity provided by JOP 80, to investigate the correspondence of the transient brightenings observed by EIT in this active region, with the ARTB previously observed by SXT and studied by Shimizu (1992). Within the simultaneous high cadence SOHO JOP 80 image sequences, both EIT and SXT accummulated a few tens of brightening events. At the time of the writing of this abstract, we can say that most of the SXT events have indeed 1 or more EIT counterparts. Typically the SXT events are somewhat bigger than the EIT events where the latter are ussualy located toward the point of origin of the SXT events. Whereas a few brightenings exist in one dataset without any trace in the other dataset (in both directions), we have additionally for a few brightenings in the SXT data, a corresponding EIT darkening as if the plasma is suddenly heated and dissappears from

  19. Dynamics and evolution of emerging active regions .

    NASA Astrophysics Data System (ADS)

    Battiato, V.; Billotta, S.; Contarino, L.; Romano, P.; Spadaro, D.; Zuccarello, F.

    In the framework of the study on active region emergence, we report the results obtained from the analysis of two ARs (NOAA 10050 and NOAA 10407), characterized by different lifetimes: recurrent the former and short-lived (7 days) the latter. The data used were acquired during two observational campaigns carried out at THEMIS telescope in IPM mode, coordinated with other instruments (IOACT, DOT, BBSO, MDI/SOHO, EIT/SOHO, TRACE). The results obtained have provided indications on the atmospheric layers where the first manifestations of the emerging AR are evidenced, on the rate of emergence of magnetic flux, on the upward velocity of AFS, on asymmetries in downward motions in the AFS legs.

  20. FIP bias in a sigmoidal active region

    NASA Astrophysics Data System (ADS)

    Baker, D.; Brooks, D. H.; Démoulin, P.; van Driel-Gesztelyi, Lidia; Green, L. M.; Steed, K.; Carlyle, J.

    2014-01-01

    We investigate first ionization potential (FIP) bias levels in an anemone active region (AR) - coronal hole (CH) complex using an abundance map derived from Hinode/EIS spectra. The detailed, spatially resolved abundance map has a large field of view covering 359'' × 485''. Plasma with high FIP bias, or coronal abundances, is concentrated at the footpoints of the AR loops whereas the surrounding CH has a low FIP bias, ~1, i.e. photospheric abundances. A channel of low FIP bias is located along the AR's main polarity inversion line containing a filament where ongoing flux cancellation is observed, indicating a bald patch magnetic topology characteristic of a sigmoid/flux rope configuration.

  1. EUV Observations of Active Region Dynamics

    NASA Astrophysics Data System (ADS)

    Deluca, E. E.; Cirtain, J. W.; del Zanna, G.; Mason, H. E.; Martens, P. C.; Schmelz, J.; Golub, L.

    2005-05-01

    Data collected during SoHO JOP 146, in collaboration with TRACE, is used to investigate the physical characteristics of coronal active region loops as a function of time and position along and across loop structures. These data include TRACE images in all three EUV passbands, and simultaneous CDS spectroscopic observations. Preliminary measurements of the loop temperature both along the loop half-length and loop cross-section are presented as a function of time. We will show the temperature and density profiles of several structures as a function of position, show changes in temperature and density with time and characterize the coronal background emission. Questions raised by these results will be greatly advanced with the high resolution spectra available from the EIS on Solar-B.

  2. Active region helicity evolution and related coronal mass ejection activity.

    NASA Astrophysics Data System (ADS)

    Green, L.; Mandrini, C.; van Driel-Gesztelyi, L.; Demoulin, P.

    The computation of magnetic helicity has become increasingly important in the studies of solar activity. Observations of helical structures in the solar atmosphere, and their subsequent ejection into the interplanetary medium, have resulted in considerable interest to find the link between the amount of helicity in the coronal magnetic field and the origin of coronal mass ejections (CMEs). This is reinforced by theory which shows magnetic helicity to be a well preserved quantity (Berger, 1984), and so with a continued injection into the corona an endless accumulation will occur. CMEs therefore provide a natural method to remove helicity from the corona. Recent works (DeVore, 2000, Chae, 2001, Chae et al., 2001, Demoulin et al., 2002, Green et al., 2002) have endeavoured to find the source of helicity in the corona to explain the observed CME activity in specific cases. The main candidates being differential rotation, shear motions or a transfer of helicity from below the photosphere into the corona. In order to establish a confident relation between CMEs and helicity, these works needs to be expanded to include CME source regions with different characteristics. A study of a very different active region will be presented and the relationship between helicity content and CME activity will be discussed in the framework of the previous studies.

  3. Molecular Probe Analysis of Mammalian Brain Acetylcholinesterase

    DTIC Science & Technology

    1988-09-27

    Project and Degrees Awarded During this Reporting Period: Judith K. Marquis, Principal Investigator Thomas Biagioni , Senior Research Technician Robert...binding sites in nerve membrane vesicles. Comp. Biochem. Physiol. 80C: 203-205 (1985). 5. Volpe, L.S., T.M. Biagioni & J.K. Marquis: In vitro modulation of...Saxena, Vol. 6(1988Y.8 11. Marquis, J.K. & T.M. Biagioni : Selective inhibition of acetylcholinesterase and butyrylcholinesterase in human plasma

  4. An evaluation of the inhibition of human butyrylcholinesterase and acetylcholinesterase by the organophosphate chlorpyrifos oxon

    SciTech Connect

    Shenouda, Josephine; Green, Paula; Sultatos, Lester

    2009-12-01

    Acetylcholinesterase (EC 3.1.1.7) and butyrylcholinesterase (EC 3.1.1.8) are enzymes that belong to the superfamily of alpha/beta-hydrolase fold proteins. While they share many characteristics, they also possess many important differences. For example, whereas they have about 54% amino acid sequence identity, the active site gorge of acetylcholinesterase is considerably smaller than that of butyrylcholinesterase. Moreover, both have been shown to display simple and complex kinetic mechanisms, depending on the particular substrate examined, the substrate concentration, and incubation conditions. In the current study, incubation of butyrylthiocholine in a concentration range of 0.005-3.0 mM, with 317 pM human butyrylcholinesterase in vitro, resulted in rates of production of thiocholine that were accurately described by simple Michaelis-Menten kinetics, with a K{sub m} of 0.10 mM. Similarly, the inhibition of butyrylcholinesterase in vitro by the organophosphate chlorpyrifos oxon was described by simple Michaelis-Menten kinetics, with a k{sub i} of 3048 nM{sup -1} h{sup -1}, and a K{sub D} of 2.02 nM. In contrast to inhibition of butyrylcholinesterase, inhibition of human acetylcholinesterase by chlorpyrifos oxon in vitro followed concentration-dependent inhibition kinetics, with the k{sub i} increasing as the inhibitor concentration decreased. Chlorpyrifos oxon concentrations of 10 and 0.3 nM gave k{sub i}s of 1.2 and 19.3 nM{sup -1} h{sup -1}, respectively. Although the mechanism of concentration-dependent inhibition kinetics is not known, the much smaller, more restrictive active site gorge of acetylcholinesterase almost certainly plays a role. Similarly, the much larger active site gorge of butyrylcholinesterase likely contributes to its much greater reactivity towards chlorpyrifos oxon, compared to acetylcholinesterase.

  5. Effect of Calea serrata Less. n-hexane extract on acetylcholinesterase of larvae ticks and brain Wistar rats.

    PubMed

    Ribeiro, Vera Lucia Sardá; Vanzella, Cláudia; Moysés, Felipe dos Santos; Santos, Jaqueline Campiol Dos; Martins, João Ricardo Souza; von Poser, Gilsane Lino; Siqueira, Ionara Rodrigues

    2012-10-26

    Acetylcholinesterase (AChE), an enzyme that hydrolyses acetylcholine (ACh) at cholinergic synapses, is a target for pesticides and its inhibition by organophosphates leads to paralysis and death of arthropods. It has been demonstrated that the n-hexane extract of Calea serrata had acaricidal activity against larvae of Rhipicephalus (Boophilus) microplus and Rhipicephalus sanguineus. The aim of the present study was to understand the mechanism of the acaricidal action of C. serrata n-hexane extract are specifically to investigate the in vitro anticholinesterase activity on larvae of R. microplus and in brain structures of male Wistar rats. The n-hexane extract significantly inhibited in vitro acetylcholinesterase activity in R. microplus larvae and rat brain structures. The results confirm that inhibition of acetylcholinesterase is a possible mechanism of action of hexane extract at C. serrata.

  6. Temperature rise and microplastics interact with the toxicity of the antibiotic cefalexin to juveniles of the common goby (Pomatoschistus microps): Post-exposure predatory behaviour, acetylcholinesterase activity and lipid peroxidation.

    PubMed

    Fonte, Elsa; Ferreira, Pedro; Guilhermino, Lúcia

    2016-11-01

    The goal of this study was to investigate the toxicity of cefalexin to Pomatoschistus microps juveniles in relation to the presence of microplastics in the water and temperature rise. After acclimatization, groups of wild juveniles were exposed for 96h to artificial salt water (control), microplastics alone (0.184mg/l), cefalexin alone (1.3-10mg/l) and in mixture with microplastics (cefalexin: 1.3-10mg/l; microplastics: 0.184mg/l) at 20 and 25°C. Effect criteria were mortality, post-exposure predatory performance (PEPP), acetylcholinesterase activity (AChE) and lipid peroxidation levels (LPO). At 20°C, concentrations of cefalexin alone≥5mg/l significantly reduced PEPP (up to 56%; 96h-EC50=8.4mg/l), indicating toxicity of the antibiotic to juveniles after short-term exposure to water concentrations in the low ppm range. At 20°C, fish exposed to microplastics alone did not have significant differences in any of the parameters tested relative to the control group but tended to have an inhibition of the PEPP (23%) and AChE (21%); at 25°C, microplastics alone caused mortality (33%) and PEPP inhibition (28%). Thus, microplastics are toxic to P. microps juveniles. At 20°C, under simultaneous exposure to cefalexin and microplastics, the PEPP was significantly reduced (at cefalexin concentrations≥1.25mg/l). Moreover, at 25°C, the toxicity curves of cefalexin (PEPP based), alone and in mixture with microplastics, were significantly different (p<0.05; 96h-EC50 of 3.8 and 5.2mg/l, respectively), and the integrated data analysis indicated significant interactions between the two substances for all biomarkers. Thus, the presence of microplastics in the water influenced the toxicity of cefalexin. The rise of water temperature (from 20°C to 25°C), increased the microplastics-induced mortality (from 8 to 33%), and the inhibitory effects of cefalexin on the PEPP (up to 70%). Significant differences (p<0.05) between the toxicity curves of cefalexin alone at distinct

  7. Concentration-Dependent Interactions of the Organophosphates Chlorpyrifos Oxon and Methyl Paraoxon with Human Recombinant Acetylcholinesterase

    PubMed Central

    Kaushik, R.; Rosenfeld, Clint A.; Sultatos, L.G.

    2007-01-01

    For many decades it has been thought that oxygen analogs (oxons) of organophosphorus insecticides phosphylate the catalytic site of acetylcholinesterase by a mechanism that follows simple Michaelis-Menten kinetics. More recently, the interactions of at least some oxons have been shown to be far more complex, and likely involve binding of oxons to a second site on acetylcholinesterase that modulates the inhibitory capacity of other oxon molecules at the catalytic site. The current study has investigated the interactions of chlorpyrifos oxon and methyl paraoxon with human recombinant acetylcholinesterase. Both chlorpyrifos oxon and methyl paraoxon were found to have ki’s that change as a function of oxon concentration. Furthermore, 10 nM chlorpyrifos oxon resulted in a transient increase in acetylthiocholine hydrolysis, followed by inhibition. Moreover, in the presence of 100 nM chlorpyrifos oxon, acetylthiocholine was found to influence both the Kd (binding affinity) and k2 (phosphorylation constant) of this oxon. Collectively, these results demonstrate that the interactions of chlorpyrifos oxon and methyl paraoxon with acetylcholinesterase cannot be described by simple Michaelis-Menten kinetics, but instead support the hypothesis that these oxons bind to a secondary site on acetylcholinesterase, leading to activation/inhibition of the catalytic site, depending on the nature of the substrate and inhibitor. Additionally, these data raise questions regarding the adequacy of estimating risk of low levels of insecticide exposure from direct extrapolation of insecticide dose-response curves since the capacity of individual oxon molecules at low oxon levels could be greater than individual oxon molecules in vivo associated with the dose response curve. PMID:17467020

  8. Concentration-dependent interactions of the organophosphates chlorpyrifos oxon and methyl paraoxon with human recombinant acetylcholinesterase

    SciTech Connect

    Kaushik, R.; Rosenfeld, Clint A.; Sultatos, L.G. . E-mail: sultatle@umdnj.edu

    2007-06-01

    For many decades it has been thought that oxygen analogs (oxons) of organophosphorus insecticides phosphorylate the catalytic site of acetylcholinesterase by a mechanism that follows simple Michaelis-Menten kinetics. More recently, the interactions of at least some oxons have been shown to be far more complex and likely involve binding of oxons to a second site on acetylcholinesterase that modulates the inhibitory capacity of other oxon molecules at the catalytic site. The current study has investigated the interactions of chlorpyrifos oxon and methyl paraoxon with human recombinant acetylcholinesterase. Both chlorpyrifos oxon and methyl paraoxon were found to have k {sub i}'s that change as a function of oxon concentration. Furthermore, 10 nM chlorpyrifos oxon resulted in a transient increase in acetylthiocholine hydrolysis, followed by inhibition. Moreover, in the presence of 100 nM chlorpyrifos oxon, acetylthiocholine was found to influence both the K {sub d} (binding affinity) and k {sub 2} (phosphorylation constant) of this oxon. Collectively, these results demonstrate that the interactions of chlorpyrifos oxon and methyl paraoxon with acetylcholinesterase cannot be described by simple Michaelis-Menten kinetics but instead support the hypothesis that these oxons bind to a secondary site on acetylcholinesterase, leading to activation/inhibition of the catalytic site, depending on the nature of the substrate and inhibitor. Additionally, these data raise questions regarding the adequacy of estimating risk of low levels of insecticide exposure from direct extrapolation of insecticide dose-response curves since the capacity of individual oxon molecules at low oxon levels could be greater than individual oxon molecules in vivo associated with the dose-response curve.

  9. The Limit of Free Magnetic Energy in Active Regions

    NASA Technical Reports Server (NTRS)

    Moore, Ron; Falconer, David; Sterling, Alphonse

    2012-01-01

    By measuring from active-region magnetograms a proxy of the free energy in the active region fs magnetic field, it has been found previously that (1) there is an abrupt upper limit to the free energy the field can hold that increases with the amount of magnetic field in the active region, the active region fs magnetic flux content, and (2) the free energy is usually near its limit when the field explodes in a CME/flare eruption. That is, explosive active regions are concentrated in a main-sequence path bordering the free-energy ]limit line in (flux content, free-energy proxy) phase space. Here, from measurement of Marshall Space Flight Center vector magnetograms, we find the magnetic condition that underlies the free ]energy limit and the accompanying main sequence of explosive active regions. Using a suitable free ]energy proxy measured from vector magnetograms of 44 active regions, we find that (1) in active regions at and near their free ]energy limit, the ratio of magnetic-shear free energy to the non ]free magnetic energy the potential field would have is approximately 1 in the core field, the field rooted along the neutral line, and (2) this ratio is progressively less in active regions progressively farther below their free ]energy limit. This shows that most active regions in which this core-field energy ratio is much less than 1 cannot be triggered to explode; as this ratio approaches 1, most active regions become capable of exploding; and when this ratio is 1 or greater, most active regions are compelled to explode. From these results we surmise the magnetic condition that determines the free ]energy limit is the ratio of the free magnetic energy to the non-free energy the active region fs field would have were it completely relaxed to its potential ]field configuration, and that this ratio is approximately 1 at the free-energy limit and in the main sequence of explosive active regions.

  10. In Vitro Acetylcholinesterase Inhibition by Type A Botulinum Toxin

    PubMed Central

    Marshall, R.; Quinn, L. Y.

    1967-01-01

    Type A botulinum toxin was studied for its ability to inhibit the action of acetyl-cholinesterase. The chromogenic substrate, indophenyl acetate, was used for assay of enzyme activity. Inhibition of enzyme function was detected through use of both 6.6 × 10−6 mg (20 ld50) and 6.6 × 10−10 mg (2 × 10−3ld50) of type A botulinal toxin. Control assays were performed by use of both homologous antitoxin and heterologous antitoxins (types B and E). Enzyme inhibition was effectively prevented by use of homologous antitoxin only. The inhibition noted was specific and reproducible for given substrate, enzyme, and toxin concentrations. PMID:4860916

  11. Acetylcholinesterase inhibitory effect of lignans isolated from Schizandra chinensis.

    PubMed

    Hung, Tran Manh; Na, MinKyun; Min, Byung Sun; Ngoc, Tran Minh; Lee, IkSoo; Zhang, XinFeng; Bae, KiHwan

    2007-06-01

    The hexane extract of the fruit of Schizandra chinensis (Schisandraceae) was found to show significant inhibition of the activity of acetylcholinesterase enzyme (AChE). In further studies, fourteen lignans were isolated, and evaluated for their inhibitory effect on AChE. The compounds having both aromatic methylenedioxy and hydroxyl groups on their cyclooctadiene ring, such as gomisin C (6), gomisin G (7), gomisin D (8), schisandrol B (11) and gomisin A (13), entirely inhibited AChE in dose dependent manners, with IC50 values of 6.71 +/- 0.53, 6.55 +/- 0.31, 7.84 +/- 0.62, 12.57 +/- 1.07 and 13.28 +/- 1.68 microM, respectively. These results indicate that the lignans could potentially be a potent class of AChE inhibitors.

  12. Carrageenans solubilize asymmetric acetylcholinesterase from nicotinic cholinergic synapses.

    PubMed

    von Bernhardi, R; Ayal, H; Inestrosa, N C

    1990-01-01

    1. Acetylcholinesterase (AChE) catalyzes the hydrolysis of acetylcholine at cholinergic synapses in both vertebrate and invertebrates organisms. 2. The asymmetric synaptic AChE is attached to the extracellular matrix (ECM) of the neuromuscular junction through heparin sulphate proteoglycans (HSPGs). 3. It has been shown previously that heparin-like glycosaminoglycans (GAGs) can solubilize this enzyme from the cholinergic synapses. 4. The present paper describes the solubilization of asymmetric AChE by different marine macroalgal polysaccharides, called carrageenans. 5. Important differences were found among all the carrageenans tested; they released 15-50% of the total AChE activity normally solubilized by heparin. 6. Carrageenans extracted from tetrasporic stages of Iridaea ciliata and I. membranacea were always better extracting agents than those from the cystocarpic stages of these algae, suggesting that lambda-like carrageenans are involved. 7. This hypothesis was confirmed by extracting AChE with purified carrageenans.

  13. Acetylcholinesterase biosensor for carbaryl detection based on interdigitated array microelectrodes.

    PubMed

    Gong, Zhili; Guo, Yemin; Sun, Xia; Cao, Yaoyao; Wang, Xiangyou

    2014-10-01

    In this study, an acetylcholinesterase (AChE) biosensor with superior accuracy and sensitivity was successfully developed based on interdigitated array microelectrodes (IAMs). IAMs have a series of parallel microband electrodes with alternating microbands connected together. Chitosan was used as the enzyme immobilization material, and AChE was used as the model enzyme for carbaryl detection to fabricate AChE biosensor. Electrochemical impedance spectroscopy was used in conjunction with the fabricated biosensor to detect pesticide residues. Based on the inhibition of pesticides on the AChE activity, using carbaryl as model compounds, the biosensor exhibited a wide range, low detection limit, and high stability. Moreover, the biosensor can also be used as a new promising tool for pesticide residue analysis.

  14. Experimental and computational studies on the inhibition of acetylcholinesterase by curcumin and some of its derivatives.

    PubMed

    Tello-Franco, Veronica; Lozada-García, Maria Concepcion; Soriano-García, Manuel

    2013-06-01

    Recent studies have demonstrated several biological activities of curcumin with therapeutic potential against Alzheimer's disease, among them the inhibition of the enzyme acetylcholinesterase (AChE). Aiming at identifying the chemical features relevant for this activity, the inhibition of curcumin and a set of 7 derivatives against AChE of E. electricus was measured. These derivatives presented lower activity than curcumin, allowing for the identification of possible unfavorable enzyme-inhibitor interactions. Our computational approach was to dock the molecules to the active site of AChE, followed by an analysis of hydrogen bonds and close contacts to relevant aromatic amino acid residues. To account for inhibitory activity, we sought to define the common structural features between known acetylcholinesterase inhibitors and the tested derivatives. A pharmacophore model was generated, which consisted of two hydrophobic, one aromatic and one hydrogen bond acceptor features. We conclude that the presence of two aromatic rings and the distance between them, allows curcumin and its derivatives to favorably interact with both the quaternary and peripheral sites of AChE. Hydrogen bonds can be formed with the quaternary and acyl sites, which should further stabilize the complex. The acylation of the hydroxyl groups and the reduction of the conjugated double bonds lowered the inhibitory activity, pointing to the modification of the keto-enol moiety as the best alternative for the design of more potent curcumin derivatives as acetylcholinesterase inhibitors.

  15. Acetylcholinesterase 1 in populations of organophosphate resistant North American strains of the cattle tick, Rhipicephalus microplus (Acari: Ixodidae)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In a collaboration with Purdue University researchers, we sequenced a 143,606 base pair Rhipicephalus microplus BAC library clone that contained the coding region for acetylcholinesterase 1 (AChE1). Sequencing was by Sanger protocols and the final assembly resulted in 15 contigs of varying length, e...

  16. Statistical Analysis of Acoustic Wave Parameters Near Solar Active Regions

    NASA Astrophysics Data System (ADS)

    Rabello-Soares, M. Cristina; Bogart, Richard S.; Scherrer, Philip H.

    2016-08-01

    In order to quantify the influence of magnetic fields on acoustic mode parameters and flows in and around active regions, we analyze the differences in the parameters in magnetically quiet regions nearby an active region (which we call “nearby regions”), compared with those of quiet regions at the same disk locations for which there are no neighboring active regions. We also compare the mode parameters in active regions with those in comparably located quiet regions. Our analysis is based on ring-diagram analysis of all active regions observed by the Helioseismic and Magnetic Imager (HMI) during almost five years. We find that the frequency at which the mode amplitude changes from attenuation to amplification in the quiet nearby regions is around 4.2 mHz, in contrast to the active regions, for which it is about 5.1 mHz. This amplitude enhacement (the “acoustic halo effect”) is as large as that observed in the active regions, and has a very weak dependence on the wave propagation direction. The mode energy difference in nearby regions also changes from a deficit to an excess at around 4.2 mHz, but averages to zero over all modes. The frequency difference in nearby regions increases with increasing frequency until a point at which the frequency shifts turn over sharply, as in active regions. However, this turnover occurs around 4.9 mHz, which is significantly below the acoustic cutoff frequency. Inverting the horizontal flow parameters in the direction of the neigboring active regions, we find flows that are consistent with a model of the thermal energy flow being blocked directly below the active region.

  17. Design and synthesis of dual inhibitors of acetylcholinesterase and serotonin transporter targeting potential agents for Alzheimer's disease.

    PubMed

    Kogen, Hiroshi; Toda, Narihiro; Tago, Keiko; Marumoto, Shinji; Takami, Kazuko; Ori, Mayuko; Yamada, Naho; Koyama, Kazuo; Naruto, Shunji; Abe, Kazumi; Yamazaki, Reina; Hara, Takao; Aoyagi, Atsushi; Abe, Yasuyuki; Kaneko, Tsugio

    2002-10-03

    Highly efficient acetylcholinesterase (AChE) and serotonin transporter (SERT) dual inhibitors, (S)-4 and (R)-13 were designed and synthesized on the basis of the hypothetical model of AChE active site. Both compounds showed potent inhibitory activities against AChE and SERT. [structure: see text

  18. Carbon-11 labeling of CP-126,998*: A radiotracer for in vivo studies of acetylcholinesterase

    SciTech Connect

    Musachio, J.L.; Flesher, J.E.; Scheffel, U.

    1996-05-01

    The study of acetylcholinesterase (AChE) via PET is of interest as reduced activity of this enzyme has been observed in Alzheimer`s disease. Our efforts to develop a radiotracer for mapping of AChE have focused on the N-benzylpiperidine benzisoxazole, CP-126,998, a highly potent (IC{sub 50}=0.48 nm) and selective inhibitor of AChE. High specific activity [C-11] CP-126,998 was synthesized (14 - 24% radiochemical yield, non-decay corrected) by treatment of the desmethyl precursor, CP-118,954, with [C-11] methyl iodide and tetrabutylammonium hydroxide in DMF. In vivo studies with [C-11] CP-126,998 in mice show that this radiotracer displays highest uptake in striatum (6.2 %ID/g), a brain region known to be rich in AChE. The (striatum-cerebellum)/cerebellar radioactivity ratio reached a maximum of 4.3 at 30 min postinjection, and this ratio decreased to 2.4 at 120 min. .Radiotracer binding was saturable in vivo by pretreatment with CP-118,954. Pretreatment of mice with diisopropylfluorophosphate (4 mg/kg i.p.), a known AChE inhibitor, significantly inhibited binding in striatum in a dose-dependent manner. Initial results suggest that [C-11] CP-126,998 may prove useful as a marker for the study of AChE in humans via PET.

  19. Inhibitory Effects of Sodium Arsenite and Acacia Honey on Acetylcholinesterase in Rats

    PubMed Central

    Odunola, Oyeronke A.; Gbadegesin, Michael A.; Sallau, Abdullahi B.; Ndidi, Uche S.; Ibrahim, Mohammed A.

    2015-01-01

    This study was conducted to investigate the effect of sodium arsenite and Acacia honey on acetylcholinesterase (AChE) activity and electrolytes in the brain and serum of Wistar rats. Male Wistar albino rats in four groups of five rats each were treated with distilled water, sodium arsenite (5 mg/kg body weight), Acacia honey (20% v/v), and sodium arsenite and Acacia honey, daily for one week. The sodium arsenite and Acacia honey significantly (P < 0.05) decreased AChE activity in the brain with the combined treatment being more potent. Furthermore, sodium arsenite and Acacia honey significantly (P < 0.05) decreased AChE activity in the serum. Strong correlation was observed between the sodium and calcium ion levels with acetylcholinesterase activity in the brain and serum. The gas chromatography mass spectrometry analysis of Acacia honey revealed the presence of a number of bioactive compounds such as phenolics, sugar derivatives, and fatty acids. These findings suggest that sodium arsenite and/or Acacia honey modulates acetylcholinesterase activities which may be explored in the management of Alzheimer's diseases but this might be counteracted by the hepatotoxicity induced by arsenics. PMID:25821630

  20. Preclinical and first-in-human evaluation of PRX-105, a PEGylated, plant-derived, recombinant human acetylcholinesterase-R

    SciTech Connect

    Atsmon, Jacob; Brill-Almon, Einat; Nadri-Shay, Carmit; Chertkoff, Raul; Alon, Sari; Shaikevich, Dimitri; Volokhov, Inna; Haim, Kirsten Y.; Bartfeld, Daniel; Shulman, Avidor; Ruderfer, Ilya; Ben-Moshe, Tehila; Shilovitzky, Orit; Soreq, Hermona; Shaaltiel, Yoseph

    2015-09-15

    PRX-105 is a plant-derived recombinant version of the human ‘read-through’ acetylcholinesterase splice variant (AChE-R). Its active site structure is similar to that of the synaptic variant, and it displays the same affinity towards organophosphorus (OP) compounds. As such, PRX-105 may serve as a bio-scavenger for OP pesticides and chemical warfare agents. To assess its potential use in prophylaxis and treatment of OP poisoning we conducted several preliminary tests, reported in this paper. Intravenous (IV) PRX-105 was administered to mice either before or after exposure to an OP toxin. All mice who received an IV dose of 50 nmol/kg PRX-105, 2 min before being exposed to 1.33 × LD{sub 50} and 1.5 × LD{sub 50} of toxin and 10 min after exposure to 1.5 × LD{sub 50} survived. The pharmacokinetic and toxicity profiles of PRX-105 were evaluated in mice and mini-pigs. Following single and multiple IV doses (50 to 200 mg/kg) no deaths occurred and no significant laboratory and histopathological changes were observed. The overall elimination half-life (t{sub ½}) in mice was 994 (± 173) min. Additionally, a first-in-human study, to assess the safety, tolerability and pharmacokinetics of the compound, was conducted in healthy volunteers. The t{sub ½} in humans was substantially longer than in mice (average 26.7 h). Despite the small number of animals and human subjects who were assessed, the fact that PRX-105 exerts a protective and therapeutic effect following exposure to lethal doses of OP, its favorable safety profile and its relatively long half-life, renders it a promising candidate for treatment and prophylaxis against OP poisoning and warrants further investigation. - Highlights: • PRX-105 is a PEGylated plant-derived recombinant human acetylcholinesterase-R. • PRX-105 is a promising bio-scavenger for organophosphorous toxins at lethal doses. • PRX-105 was shown to protect animals both prophylactically and post-poisoning. • First-in-human study

  1. In vitro inhibition of acetylcholinesterase from four marine species by organophosphates and carbamates

    SciTech Connect

    Galgani, F.; Bocquene, G. )

    1990-08-01

    The literature on the biological, physical, and pharmaceutical chemistry of cholinesterase is considerable and includes data on activators and inhibitors. Most of the work on specific anticholinesterasic agents has been concerned with carbamates and organophosphates. Because of the sensitivity of acetylcholinesterase to carbamates and organophosphates, the enzyme has been used as a biochemical indicator of pollution by these agents. However, the chemical reactivity of such chemicals has not been correlated with their effect on Ache and it is impossible to accurately predict biological effects based only on structure. The objectives of this study were to investigate the sensitivity of various marine animals to both organo-phosphates and carbamates. The study was conducted by assessing the in vitro effect of five organophosphates and three carbamates on acetylcholinesterase activity from the muscle of the shrimp Palaemon serratus, the fishes Scomber and Pleuronectes platessa, and from the whole mussels Mytilus edulis. All these species could be used for the monitoring of effect of pollutants.

  2. Technique for inferring sizes of stellar-active regions

    SciTech Connect

    Dobson-Hockey, A.K.; Radick, R.R.

    1986-01-01

    Inspection of spectroheliograms showing large, well-developed active regions generally show the sunspots to lead the associated plage, in the sense of the solar rotation. Measurements have been made from spectroheliograms of spot-plage offsets and compared with nearly contemporaneous integrated disk observations. Larger active regions generally show larger spot leads; however, information regarding active-region sizes and spot-plage offsets is not readily obtainable form stellar-type observations of the Sun.

  3. Tracked Active Region Patches for MDI and HMI

    NASA Astrophysics Data System (ADS)

    Turmon, Michael; Hoeksema, J. Todd; Bobra, Monica

    2014-06-01

    We describe tracked active-region patch data products that have been developed for HMI (HMI Active Region Patches, or HARPs) and for MDI (MDI Tracked Active Region Patches, or MDI TARPs). Both data products consist of tracked magnetic features on the scale of solar active regions. The now-released HARP data product covers 2010-present (>2000 regions to date). Like the HARPs, the MDI TARP data set is a catalog of active regions (ARs), indexed by a region ID number, analogous to a NOAA AR number, and time. The TARPs contain 6170 regions spanning 72000 images taken over 1996-2010, and will be availablein the MDI resident archive (RA).MDI TARPs are computed based on the 96-minute synoptic magnetograms and intensitygrams. As with the related HARP data product, the approximate threshold for significance is 100G. Use of both image types together allows faculae and sunspots to be separated out as sub-classes of activity, in addition to identifying the overall active region that they are in. After being identified in single images, the magnetically-active patches are grouped and tracked from image to image. Merges among growing active regions, as well as faint active regions hovering at the threshold of detection, are handled automatically. Regions are tracked from their inception until they decay within view, or transit off the visible disk. For each active region and for each time, a bitmap image is stored containing the precise outline of the active region. Also, metadata such as areas and integrated fluxes are stored for each AR and for each time. Because there is a cross-calibration between the HMI and MDI magnetograms (Liu et al. 2012), it is straightforward to use the same classification and tracking rules for the HMI HARPs and the MDI TARPs. We show results demonstrating region correspondence, region boundary agreement, and agreement of flux metadata using the approximately 140 regions in the May 2010-October 2010 time period. We envision several uses for these data

  4. A Fractal Dimension Survey of Active Region Complexity

    NASA Technical Reports Server (NTRS)

    McAteer, R. T. James; Gallagher, Peter; Ireland, Jack

    2005-01-01

    A new approach to quantifying the magnetic complexity of active regions using a fractal dimension measure is presented. This fully-automated approach uses full disc MDI magnetograms of active regions from a large data set (2742 days of the SoHO mission; 9342 active regions) to compare the calculated fractal dimension to both Mount Wilson classification and flare rate. The main Mount Wilson classes exhibit no distinct fractal dimension distribution, suggesting a self-similar nature of all active regions. Solar flare productivity exhibits an increase in both the frequency and GOES X-ray magnitude of flares from regions with higher fractal dimensions. Specifically a lower threshold fractal dimension of 1.2 and 1.25 exists as a necessary, but not sufficient, requirement for an active region to produce M- and X-class flares respectively .

  5. GLOBAL DYNAMICS OF SUBSURFACE SOLAR ACTIVE REGIONS

    SciTech Connect

    Jouve, L.; Brun, A. S.

    2013-01-01

    We present three-dimensional numerical simulations of a magnetic loop evolving in either a convectively stable or unstable rotating shell. The magnetic loop is introduced into the shell in such a way that it is buoyant only in a certain portion in longitude, thus creating an {Omega}-loop. Due to the action of magnetic buoyancy, the loop rises and develops asymmetries between its leading and following legs, creating emerging bipolar regions whose characteristics are similar to those of observed spots at the solar surface. In particular, we self-consistently reproduce the creation of tongues around the spot polarities, which can be strongly affected by convection. We further emphasize the presence of ring-shaped magnetic structures around our simulated emerging regions, which we call 'magnetic necklace' and which were seen in a number of observations without being reported as of today. We show that those necklaces are markers of vorticity generation at the periphery and below the rising magnetic loop. We also find that the asymmetry between the two legs of the loop is crucially dependent on the initial magnetic field strength. The tilt angle of the emerging regions is also studied in the stable and unstable cases and seems to be affected both by the convective motions and the presence of a differential rotation in the convective cases.

  6. OBSERVING CORONAL NANOFLARES IN ACTIVE REGION MOSS

    SciTech Connect

    Testa, Paola; DeLuca, Ed; Golub, Leon; Korreck, Kelly; Weber, Mark; De Pontieu, Bart; Martinez-Sykora, Juan; Title, Alan; Hansteen, Viggo; Cirtain, Jonathan; Winebarger, Amy; Kobayashi, Ken; Kuzin, Sergey; Walsh, Robert; DeForest, Craig

    2013-06-10

    The High-resolution Coronal Imager (Hi-C) has provided Fe XII 193A images of the upper transition region moss at an unprecedented spatial ({approx}0.''3-0.''4) and temporal (5.5 s) resolution. The Hi-C observations show in some moss regions variability on timescales down to {approx}15 s, significantly shorter than the minute-scale variability typically found in previous observations of moss, therefore challenging the conclusion of moss being heated in a mostly steady manner. These rapid variability moss regions are located at the footpoints of bright hot coronal loops observed by the Solar Dynamics Observatory/Atmospheric Imaging Assembly in the 94 A channel, and by the Hinode/X-Ray Telescope. The configuration of these loops is highly dynamic, and suggestive of slipping reconnection. We interpret these events as signatures of heating events associated with reconnection occurring in the overlying hot coronal loops, i.e., coronal nanoflares. We estimate the order of magnitude of the energy in these events to be of at least a few 10{sup 23} erg, also supporting the nanoflare scenario. These Hi-C observations suggest that future observations at comparable high spatial and temporal resolution, with more extensive temperature coverage, are required to determine the exact characteristics of the heating mechanism(s).

  7. Influence of acetylcholinesterase immobilization on the photoluminescence properties of mesoporous silicon surface

    NASA Astrophysics Data System (ADS)

    Saleem, Muhammad; Rafiq, Muhammad; Seo, Sung-Yum; Lee, Ki Hwan

    2014-07-01

    Acetylcholinesterase immobilized p-type porous silicon surface was prepared by covalent attachment. The immobilization procedure was based on support surface chemical oxidation, silanization, surface activation with cyanuric chloride and finally covalent attachment of free enzyme on the cyanuric chloride activated porous silicon surface. Different pore diameter of porous silicon samples were prepared by electrochemical etching in HF based electrolyte solution and appropriate sample was selected suitable for enzyme immobilization with maximum trapping ability. The surface modification was studied through field emission scanning electron microscope, EDS, FT-IR analysis, and photoluminescence measurement by utilizing the fluctuation in the photoluminescence of virgin and enzyme immobilized porous silicon surface. Porous silicon showed strong photoluminescence with maximum emission at 643 nm and immobilization of acetylcholinesterase on porous silicon surface cause considerable increment on the photoluminescence of porous silicon material while acetylcholinesterase free counterpart did not exhibit any fluorescence in the range of 635-670 nm. The activities of the free and immobilized enzymes were evaluated by spectrophotometric method by using neostigmine methylsulfate as standard enzyme inhibitor. The immobilized enzyme exhibited considerable response toward neostigmine methylsulfate in a dose dependent manner comparable with that of its free counterpart alongside enhanced stability, easy separation from the reaction media and significant saving of enzyme. It was believed that immobilized enzyme can be exploited in organic and biomolecule synthesis possessing technical and economical prestige over free enzyme and prominence of easy separation from the reaction mixture.

  8. Different inhibition of acetylcholinesterase in selected parts of the rat brain following intoxication with VX and Russian VX.

    PubMed

    Hajek, Petr; Bajgar, Jiri; Slizova, Dasa; Krs, Otakar; Kuca, Kamil; Capek, Lukas; Fusek, Josef

    2009-01-01

    Differences between acetylcholinesterase (AChE) inhibition in the brain structures following VX and RVX exposure are not known as well as information on the possible correlation of biochemical and histochemical methods detecting AChE activity. Therefore, inhibition of AChE in different brain parts detected by histochemical and biochemical techniques was compared in rats intoxicated with VX and RVX. AChE activities in defined brain regions 30 min after treating rats with VX and Russian VX intramuscularly (1.0 x LD(50)) were determined by using biochemical and histochemical methods. AChE inhibition was less expressed for RVX, in comparison with VX. Frontal cortex and pontomedullar areas containing ncl. reticularis has been found as the most sensitive areas for the action of VX. For RVX, these structures were determined to be frontal cortex, dorsal septum, and hippocampus, respectively. Histochemical and biochemical results were in good correlation (R(xy) = 0.8337). Determination of AChE activity in defined brain structures was a more sensitive parameter for VX or RVX exposure than the determination of AChE activity in the whole-brain homogenate. This activity represents a "mean" of the activities in different structures. Thus, AChE activity is the main parameter investigated in studies searching for target sites following nerve-agent poisoning contributing to better understanding of toxicodynamics of nerve agents.

  9. Some enzymatic properties of brain Acetylcholinesterase from bluegill and channel catfish

    USGS Publications Warehouse

    Hogan, James W.; Knowles, Charles O.

    1968-01-01

    Using a manometric technique an acetylcholinesterase (EC 3.1.1.7, acetylcholine acetyl-hydrolase) was demonstrated in brain tissue from the bluegill, Lepomis macrochirus Rafinesque, and the channel catfish, Ictalurus punctatus (Walbaum). The activities were 19 and 37 μmoles acetylcholine hydrolyzed/milligram protein per hour for the bluegill and channel catfish enzymes, respectively. The optimum substrate concentration for the hydrolysis of acetylcholine was 10 mMfor the enzymes from both species. Generally, the catfish acetylcholinesterase was somewhat more susceptible than the bluegill to the inhibitors tested; however, the bluegill enzyme was more susceptible to inhibition by malathion and malaoxon.

  10. Molecular Dynamics of Mouse Acetylcholinesterase Complexed with Huperzine A

    SciTech Connect

    Tara, Sylvia; Helms, Volkhard H.; Straatsma, TP; Mccammon, J Andrew A.

    1999-03-16

    Two molecular dynamics simulations were performed for a modeled complex of mouse acetylcholinesterase liganded with huperzine A (HupA). Analysis of these simulations shows that HupA shifts in the active site toward Tyr 337 and Phe 338, and that several residues in the active site area reach out to make hydrogen bonds with the inhibitor. Rapid fluctuations of the gorge width are observed, ranging from widths that allow substrate access to the active site, to pinched structures that do not allow access of molecules as small as water. Additional openings or channels to the active site are found. One opening is formed in the side wall of the active site gorge by residues Val 73, Asp 74, Thr 83, Glu 84, and Asn 87. Another opening is formed at the base of the gorge by residues Trp 86, Val 132, Glu 202, Gly 448, and Ile 451. Both of these openings have been observed separately in the Torpedo californica form of the enzyme. These channels could allow transport of waters and ions to and from the bulk solution.

  11. Software Displays Data on Active Regions of the Sun

    NASA Technical Reports Server (NTRS)

    Golightly, Mike; Weyland, Mark; Raben, Vern

    2011-01-01

    The Solar Active Region Display System is a computer program that generates, in near real time, a graphical display of parameters indicative of the spatial and temporal variations of activity on the Sun. These parameters include histories and distributions of solar flares, active region growth, coronal mass ejections, size, and magnetic configuration. By presenting solar-activity data in graphical form, this program accelerates, facilitates, and partly automates what had previously been a time-consuming mental process of interpretation of solar-activity data presented in tabular and textual formats. Intended for original use in predicting space weather in order to minimize the exposure of astronauts to ionizing radiation, the program might also be useful on Earth for predicting solar-wind-induced ionospheric effects, electric currents, and potentials that could affect radio-communication systems, navigation systems, pipelines, and long electric-power lines. Raw data for the display are obtained automatically from the Space Environment Center (SEC) of the National Oceanic and Atmospheric Administration (NOAA). Other data must be obtained from the NOAA SEC by verbal communication and entered manually. The Solar Active Region Display System automatically accounts for the latitude dependence of the rate of rotation of the Sun, by use of a mathematical model that is corrected with NOAA SEC active-region position data once every 24 hours. The display includes the date, time, and an image of the Sun in H light overlaid with latitude and longitude coordinate lines, dots that mark locations of active regions identified by NOAA, identifying numbers assigned by NOAA to such regions, and solar-region visual summary (SRVS) indicators associated with some of the active regions. Each SRVS indicator is a small pie chart containing five equal sectors, each of which is color-coded to provide a semiquantitative indication of the degree of hazard posed by one aspect of the activity at

  12. Inhibitors of Acetylcholinesterase and Butyrylcholinesterase Meet Immunity

    PubMed Central

    Pohanka, Miroslav

    2014-01-01

    Acetylcholinesterase (AChE) inhibitors are widely used for the symptomatic treatment of Alzheimer’s disease and other dementias. More recent use is for myasthenia gravis. Many of these inhibitors interact with the second known cholinesterase, butyrylcholinesterase (BChE). Further, evidence shows that acetylcholine plays a role in suppression of cytokine release through a “cholinergic anti-inflammatory pathway” which raises questions about the role of these inhibitors in the immune system. This review covers research and discussion of the role of the inhibitors in modulating the immune response using as examples the commonly available drugs, donepezil, galantamine, huperzine, neostigmine and pyridostigmine. Major attention is given to the cholinergic anti-inflammatory pathway, a well-described link between the central nervous system and terminal effector cells in the immune system. PMID:24893223

  13. Reading cinnamon activates olfactory brain regions.

    PubMed

    González, Julio; Barros-Loscertales, Alfonso; Pulvermüller, Friedemann; Meseguer, Vanessa; Sanjuán, Ana; Belloch, Vicente; Avila, César

    2006-08-15

    Some words immediately and automatically remind us of odours, smells and scents, whereas other language items do not evoke such associations. This study investigated, for the first time, the abstract linking of linguistic and odour information using modern neuroimaging techniques (functional MRI). Subjects passively read odour-related words ('garlic', 'cinnamon', 'jasmine') and neutral language items. The odour-related terms elicited activation in the primary olfactory cortex, which include the piriform cortex and the amygdala. Our results suggest the activation of widely distributed cortical cell assemblies in the processing of olfactory words. These distributed neuron populations extend into language areas but also reach some parts of the olfactory system. These distributed neural systems may be the basis of the processing of language elements, their related conceptual and semantic information and the associated sensory information.

  14. Characterization of lipid-protein interactions in acetylcholinesterase lipoprotein extracted from bovine erythrocytes.

    PubMed Central

    Beauregard, G; Roufogalis, B D

    1979-01-01

    Acetylcholinesterase was released from bovine erythrocytes in hypo-osmotic sodium phosphate buffer. Initially, about 30% of the enzyme was released in a soluble lipoprotein form, and further incubation resulted in the progressive release of the enzyme in a particulate form. Solubilization of the acetylcholinesterase in the particulate fraction with Lubrol WX (2 mg/ml) resulted in the loss of all lipids except a non-exchangeable fraction identified as cardiolipin. Addition of a mixture of erythrocyte phospholipids to the soluble forms and to the Lubrol WX-solubilized enzyme resulted in the formation of particulate forms of the enzyme with increased partial specific volume and Stokes radius, and a break in the Arrhenius plot of the enzyme activity around 20 degrees C. The break in the Arrhenius plot was abolished by treatment of a soluble enzyme preparation with 1.8 M salt (NaCl) in phosphate buffer, conditions that allowed the extraction of cardiolipin from the enzyme by chloroform/methanol. Failure of the high-salt treatment to decrease the Stokes radius made it unlikely that the bound cardiolipin formed a boundary layer or annulus around the protein. It is suggested that cardiolipin is bound to the core of the dimeric protein structure, thereby controlling the acetylcholinesterase activity. PMID:475749

  15. Recent developments in the synthesis of acetylcholinesterase inhibitors.

    PubMed

    Marco, José L; Carreiras, M Carmo

    2003-09-01

    The acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory activities of a series of pyrano[2,3-b]quinolines (2, 3), [1,8]naphthyridines (5, 6), 4-amino-2,3-diaryl-5,6,7,8-tetrahydrofuro[2,3-b]quinolines (11-13)/ 4-amino-6,7,8,9-tetrahydro-2,3-diphenyl-5H-cyclohepta[e]furo[2,3-b]pyridine (14), 4-amino-5,6,7,8-tetrahydro-2,3-diphenylthieno[2,3-b]quinoline (15)/ 4-amino-6,7,8,9-tetrahydro-2,3-diphenyl-5H-cyclohepta[e]thieno[2,3-b]pyridine (16) are described. These compounds are tacrine analogues that have been prepared from readily available polyfunctionalized ethyl [6-amino-5-cyano-4H-pyran]-3-carboxylates (9, 10), ethyl [6-amino-5-cyanopyridine]-3-carboxylates (7, 8), 2-amino-3-cyano-4,5-diarylfurans (17-19) and 2-amino-3-cyano-4,5-diphenylthiophene (20) via Friedländer condensation with selected ketones. These compounds are competitive and, in a few cases, non-competitive inhibitors for AChE, the most potent being compound (14), though three-fold less active than tacrine. The BuChE inhibitory activity is only significant in compounds 11 and 14, ten-fold less active than tacrine. Furthermore, the products 12 and 13 are selective and moderate AChE inhibitors.

  16. 3D MHD Models of Active Region Loops

    NASA Technical Reports Server (NTRS)

    Ofman, Leon

    2004-01-01

    Present imaging and spectroscopic observations of active region loops allow to determine many physical parameters of the coronal loops, such as the density, temperature, velocity of flows in loops, and the magnetic field. However, due to projection effects many of these parameters remain ambiguous. Three dimensional imaging in EUV by the STEREO spacecraft will help to resolve the projection ambiguities, and the observations could be used to setup 3D MHD models of active region loops to study the dynamics and stability of active regions. Here the results of 3D MHD models of active region loops are presented, and the progress towards more realistic 3D MHD models of active regions. In particular the effects of impulsive events on the excitation of active region loop oscillations, and the generation, propagations and reflection of EIT waves are shown. It is shown how 3D MHD models together with 3D EUV observations can be used as a diagnostic tool for active region loop physical parameters, and to advance the science of the sources of solar coronal activity.

  17. Morphinans and isoquinolines: acetylcholinesterase inhibition, pharmacophore modeling, and interaction with opioid receptors.

    PubMed

    Schuster, Daniela; Spetea, Mariana; Music, Melisa; Rief, Silvia; Fink, Monika; Kirchmair, Johannes; Schütz, Johannes; Wolber, Gerhard; Langer, Thierry; Stuppner, Hermann; Schmidhammer, Helmut; Rollinger, Judith M

    2010-07-15

    Following indications from pharmacophore-based virtual screening of natural product databases, morphinan and isoquinoline compounds were tested in vitro for acetylcholinesterase (AChE) inhibition. After the first screen, active and inactive compounds were used to build a ligand-based pharmacophore model in order to prioritize compounds for biological testing. Among the virtual hits tested, the enrichment of actives was significantly higher than in a random selection of test compounds. The most active compounds were biochemically tested for their activity on mu, delta, and kappa opioid receptors.

  18. ACTIVE REGION MORPHOLOGIES SELECTED FROM NEAR-SIDE HELIOSEISMIC DATA

    SciTech Connect

    MacDonald, G. A.; McAteer, R. T. J.; Henney, C. J.; Arge, C. N.; Díaz Alfaro, M.; González Hernández, I.; Lindsey, C.

    2015-07-01

    We estimate the morphology of near-side active regions using near-side helioseismology. Active regions from two data sets, Air Force Data Assimilative Photospheric flux Transport synchronic maps and Global Oscillation Network Group near-side helioseismic maps, were matched and their morphologies compared. Our algorithm recognizes 382 helioseismic active regions between 2002 April 25 and 2005 December 31 and matches them to their corresponding magnetic active regions with 100% success. A magnetic active region occupies 30% of the area of its helioseismic signature. Recovered helioseismic tilt angles are in good agreement with magnetic tilt angles. Approximately 20% of helioseismic active regions can be decomposed into leading and trailing polarity. Leading polarity components show no discernible scaling relationship, but trailing magnetic polarity components occupy approximately 25% of the area of the trailing helioseismic component. A nearside phase-magnetic calibration is in close agreement with a previous far-side helioseismic calibration and provides confidence that these morphological relationships can be used with far-side helioseismic data. Including far-side active region morphology in synchronic maps will have implications for coronal magnetic topology predictions and solar wind forecasts.

  19. Active Region Morphologies Selected From Near-side Helioseismic Data

    NASA Astrophysics Data System (ADS)

    MacDonald, Gordon Andrew; Henney, Carl; Diaz Alfaro, Manuel; Gonzalez Hernandez, Irene; Arge, Nick; Lindsey, Charles; McAteer, James

    2015-04-01

    We estimate the morphology of near-side active regions using near-side helioseismology. Active regions from two data sets, ADAPT synchronic maps and GONG near-side helioseismic maps, were matched and their morphologies compared. Our algorithm recognizes 382 helioseismic active regions between 2002 April 25 and 2005 December 31 and matches them to their corresponding magnetic active regions with 100% success. A magnetic active region occupies 30% of the area of its helioseismic signature. Recovered helioseismic tilt angles are in good agreement with magnetic tilt angles. Approximately 20% of helioseismic active regions can be decomposed into leading and trailing polarity. Leading polarity components show no discernible scaling relationship, but trailing magnetic polarity components occupy approximately 25% of the area of the trailing helioseismic component. A nearside phase-magnetic calibration is in close agreement with a previous far-side helioseismic calibration and provides confidence that these morphological relationships can be used with far-side helioseismic data. Including far-side active region morphology in synchronic maps will have implications for coronal magnetic topology predictions and solar wind forecasts.

  20. Active Region Morphologies Selected from Near-side Helioseismic Data

    NASA Astrophysics Data System (ADS)

    MacDonald, G. A.; Henney, C. J.; Díaz Alfaro, M.; González Hernández, I.; Arge, C. N.; Lindsey, C.; McAteer, R. T. J.

    2015-07-01

    We estimate the morphology of near-side active regions using near-side helioseismology. Active regions from two data sets, Air Force Data Assimilative Photospheric flux Transport synchronic maps and Global Oscillation Network Group near-side helioseismic maps, were matched and their morphologies compared. Our algorithm recognizes 382 helioseismic active regions between 2002 April 25 and 2005 December 31 and matches them to their corresponding magnetic active regions with 100% success. A magnetic active region occupies 30% of the area of its helioseismic signature. Recovered helioseismic tilt angles are in good agreement with magnetic tilt angles. Approximately 20% of helioseismic active regions can be decomposed into leading and trailing polarity. Leading polarity components show no discernible scaling relationship, but trailing magnetic polarity components occupy approximately 25% of the area of the trailing helioseismic component. A nearside phase-magnetic calibration is in close agreement with a previous far-side helioseismic calibration and provides confidence that these morphological relationships can be used with far-side helioseismic data. Including far-side active region morphology in synchronic maps will have implications for coronal magnetic topology predictions and solar wind forecasts.

  1. A Multi Wavelength Study of Active Region Development

    NASA Astrophysics Data System (ADS)

    Lara, A.; Gopalswamy, N.; Kundu, M. R.; Perez-Enriquez, R.; Koshiishi, H.; Enome, S.

    1996-05-01

    We report on a study of the evolution of several active regions during 1993 April 17-28 using data obtained at multiple wavelengths that probe various heights of the active region corona. We use simultaneous microwave (1.5 and 17 GHz) and Soft X-ray images obtained by the Very Large Array (VLA), the Nobeyama Radio Heliograph (NRH) and the Soft X-ray Telescope (SXT) on board the Yohkoh spacecraft. We also use photospheric magnetograms from Kitt Peak National Observatory to study the development of Solar Active Regions. We have followed the development of various observed parameters such as brightness temperature and polarization using radio images. The X-ray data were used to track the development of density and temperature of active regions. Using the fact that the quiet active region radiation is thermal and adopting proper emission mechanism at each frequency domain, we construct a consistent picture for the three dimensional structure of the active regions. Particular attention has been paid to the mode coupling observed at 17 GHz while the active regions crossed the solar disk.

  2. Acetylcholinesterase as a Biomarker in Environmental and Occupational Medicine: New Insights and Future Perspectives

    PubMed Central

    Caricato, Roberto; Calisi, Antonio; Giordano, Maria Elena; Schettino, Trifone

    2013-01-01

    Acetylcholinesterase (AChE) is a key enzyme in the nervous system. It terminates nerve impulses by catalysing the hydrolysis of neurotransmitter acetylcholine. As a specific molecular target of organophosphate and carbamate pesticides, acetylcholinesterase activity and its inhibition has been early recognized to be a human biological marker of pesticide poisoning. Measurement of AChE inhibition has been increasingly used in the last two decades as a biomarker of effect on nervous system following exposure to organophosphate and carbamate pesticides in occupational and environmental medicine. The success of this biomarker arises from the fact that it meets a number of characteristics necessary for the successful application of a biological response as biomarker in human biomonitoring: the response is easy to measure, it shows a dose-dependent behavior to pollutant exposure, it is sensitive, and it exhibits a link to health adverse effects. The aim of this work is to review and discuss the recent findings about acetylcholinesterase, including its sensitivity to other pollutants and the expression of different splice variants. These insights open new perspective for the future use of this biomarker in environmental and occupational human health monitoring. PMID:23936791

  3. Synthesis and in vitro acetylcholinesterase and butyrylcholinesterase inhibitory potential of hydrazide based Schiff bases.

    PubMed

    Rahim, Fazal; Ullah, Hayat; Taha, Muhammad; Wadood, Abdul; Javed, Muhammad Tariq; Rehman, Wajid; Nawaz, Mohsan; Ashraf, Muhammad; Ali, Muhammad; Sajid, Muhammad; Ali, Farman; Khan, Muhammad Naseem; Khan, Khalid Mohammed

    2016-10-01

    To discover multifunctional agents for the treatment of Alzheimer's disease, a series of hydrazide based Schiff bases were designed and synthesized based on multitarget-directed strategy. We have synthesized twenty-eight analogs of hydrazide based Schiff bases, characterized by various spectroscopic techniques and evaluated in vitro for acetylcholinesterase and butyrylcholinesterase inhibition. All compounds showed varied degree of acetylcholinesterase and butyrylcholinesterase inhibition when compared with standard Eserine. Among the series, compounds 10, 3 and 24 having IC50 values 4.12±0.01, 8.12±0.01 and 8.41±0.06μM respectively showed potent acetylcholinesterase inhibition when compared with Eserine (IC50=0.85±0.0001μM). Three compounds 13, 24 and 3 having IC50 values 6.51±0.01, 9.22±0.07 and 37.82±0.14μM respectively showed potent butyrylcholinesterase inhibition by comparing with eserine (IC50=0.04±0.0001μM). The remaining compounds also exhibited moderate to weak inhibitory potential. Structure activity relationship has been established. Through molecular docking studies the binding interaction was confirmed.

  4. Acetylcholinesterase as a biomarker in environmental and occupational medicine: new insights and future perspectives.

    PubMed

    Lionetto, Maria Giulia; Caricato, Roberto; Calisi, Antonio; Giordano, Maria Elena; Schettino, Trifone

    2013-01-01

    Acetylcholinesterase (AChE) is a key enzyme in the nervous system. It terminates nerve impulses by catalysing the hydrolysis of neurotransmitter acetylcholine. As a specific molecular target of organophosphate and carbamate pesticides, acetylcholinesterase activity and its inhibition has been early recognized to be a human biological marker of pesticide poisoning. Measurement of AChE inhibition has been increasingly used in the last two decades as a biomarker of effect on nervous system following exposure to organophosphate and carbamate pesticides in occupational and environmental medicine. The success of this biomarker arises from the fact that it meets a number of characteristics necessary for the successful application of a biological response as biomarker in human biomonitoring: the response is easy to measure, it shows a dose-dependent behavior to pollutant exposure, it is sensitive, and it exhibits a link to health adverse effects. The aim of this work is to review and discuss the recent findings about acetylcholinesterase, including its sensitivity to other pollutants and the expression of different splice variants. These insights open new perspective for the future use of this biomarker in environmental and occupational human health monitoring.

  5. Flavonoids induce the expression of acetylcholinesterase in cultured osteoblasts.

    PubMed

    Xu, Miranda L; Bi, Cathy W C; Kong, Ava Y Y; Dong, Tina T X; Wong, Yung H; Tsim, Karl W K

    2016-11-25

    Flavonoids, a group of natural compounds mainly derived from plants, are known to possess osteogenic effects in bone cells. Here, we aimed to test if flavonoid could induce a cholinergic enzyme, acetylcholinesterase (AChE), as well as bone differentiation. In cultured rat osteoblasts, twenty flavonoids, deriving from Chinese herbs and having known induction of alkaline phosphatase (ALP(1)) expression, were tested for its induction activity on AChE expression. Eleven flavonoids showed the induction, and five of them had robust activation of AChE expression, including baicalin, calycosin, genistin, hyperin and pratensein: the induction of AChE included the levels of mRNA, protein and enzymatic activity. Moreover, the flavonoid-induced AChE expression in cultured osteoblast was in proline-rich membrane anchor (PRiMA)-linked tetrameric globular form (G4) only. In parallel, the expression of PRiMA was also induced by the application of flavonoids. The flavonoid-induced AChE in the cultures was not affected by estrogen receptor blocker, ICI 182,780. Taken together, the induction of PRiMA-linked AChE in osteoblast should be independent to classical estrogen signaling pathway.

  6. Perspectives for the structure-based design of acetylcholinesterase reactivators.

    PubMed

    Ochoa, Rodrigo; Rodriguez, Carlos A; Zuluaga, Andres F

    2016-07-01

    Rational design of active molecules through structure-based methods has been gaining adepts during the last decades due to the wider availability of protein structures, most of them conjugated with relevant ligands. Acetylcholinesterase (AChE) is a molecular target with a considerable amount of data related to its sequence and 3-dimensional structure. In addition, there are structural insights about the mechanism of action of the natural substrate and drugs used in Alzheimer's disease, organophosphorus compounds, among others. We looked for AChE structural data useful for in silico design of potential interacting molecules. In particular, we focused on information regarding the design of ligands aimed to reactivate AChE catalytic activity. The structures of 178 AChE were annotated and categorized on different subsets according to the nature of the ligand, source organisms and experimental details. We compared sequence homology among the active site from Torpedo californica, Mus musculus and Homo sapiens with the latter two species having the closest relationship (88.9% identity). In addition, the mechanism of organophosphorus binding and the design of effective reactivators are reviewed. A curated data collection obtained with information from several sources was included for researchers working on the field. Finally, a molecular dynamics simulation with human AChE indicated that the catalytic pocket volume stabilizes around 600 Å(3), providing additional clues for drug design.

  7. Exposure to ethanol during neurodevelopment modifies crucial offspring rat brain enzyme activities in a region-specific manner.

    PubMed

    Stolakis, Vasileios; Liapi, Charis; Zarros, Apostolos; Kalopita, Konstantina; Memtsas, Vassilios; Botis, John; Tsagianni, Anastasia; Kimpizi, Despoina; Varatsos, Alexios; Tsakiris, Stylianos

    2015-12-01

    The experimental simulation of conditions falling within "the fetal alcohol spectrum disorder" (FASD) requires the maternal exposure to ethanol (EtOH) during crucial neurodevelopmental periods; EtOH has been linked to a number of neurotoxic effects on the fetus, which are dependent upon the extent and the magnitude of the maternal exposure to EtOH and for which very little is known with regard to the exact mechanism(s) involved. The current study has examined the effects of moderate maternal exposure to EtOH (10 % v/v in the drinking water) throughout gestation, or gestation and lactation, on crucial 21-day-old offspring Wistar rat brain parameters, such as the activities of acetylcholinesterase (AChE) and two adenosine triphosphatases (Na(+),K(+)-ATPase and Mg(2+)-ATPase), in major offspring CNS regions (frontal cortex, hippocampus, hypothalamus, cerebellum and pons). The implemented experimental setting has provided a comparative view of the neurotoxic effects of maternal exposure to EtOH between gestation alone and a wider exposure timeframe that better covers the human third trimester-matching CNS neurodevelopment period (gestation and lactation), and has revealed a CNS region-specific susceptibility of the examined crucial neurochemical parameters to the EtOH exposure schemes attempted. Amongst these parameters, of particular importance is the recorded extensive stimulation of Na(+),K(+)-ATPase in the frontal cortex of the EtOH-exposed offspring that seems to be a result of the deleterious effect of EtOH during gestation. Although this stimulation could be inversely related to the observed inhibition of AChE in the same CNS region, its dependency upon the EtOH-induced modulation of other systems of neurotransmission cannot be excluded and must be further clarified in future experimental attempts aiming to simulate and to shed more light on the milder forms of the FASD-related pathophysiology.

  8. Regional Observation of Seismic Activity in Baekdu Mountain

    NASA Astrophysics Data System (ADS)

    Kim, Geunyoung; Che, Il-Young; Shin, Jin-Soo; Chi, Heon-Cheol

    2015-04-01

    Seismic unrest in Baekdu Mountain area between North Korea and Northeast China region has called attention to geological research community in Northeast Asia due to her historical and cultural importance. Seismic bulletin shows level of seismic activity in the area is higher than that of Jilin Province of Northeast China. Local volcanic observation shows a symptom of magmatic unrest in period between 2002 and 2006. Regional seismic data have been used to analyze seismic activity of the area. The seismic activity could be differentiated from other seismic phenomena in the region by the analysis.

  9. Can Salivary Acetylcholinesterase be a Diagnostic Biomarker for Alzheimer?

    PubMed Central

    Bakhtiari, Sedigheh; Moghadam, Nahid Beladi; Ehsani, Marjan; Mortazavi, Hamed; Sabour, Siamak

    2017-01-01

    Introduction The loss of brain cholinergic activity is a key phenomenon in the biochemistry of Alzheimer’s Disease (AD). Due to the specific biosynthesis of Acetylcholinesterase (AChE) of cholinergic neurons, the enzyme has been proposed as a potential biochemical marker of cholinergic activity. AChE is expressed not only in the Central Nervous System (CNS), Peripheral Nervous System (PNS) and muscles, but also on the surface of blood cells and saliva. Aim This study aimed to measure salivary AChE activity in AD and to determine the feasibility of creating a simple laboratory test for diagnosing such patients. Materials and Methods In this cross-sectional study, the recorded data were obtained from 15 Alzheimer’s patients on memantine therapy and 15 healthy subjects. Unstimulated whole saliva samples were collected from the participants and salivary levels of AChE activity were determined by using the Ellman colorimetric method. The Mann Whitney U test was used to compare the average (median) of AChE activity between AD and controls. In order to adjust for possible confounding factors, partial correlation coefficient and multivariate linear regressions were used. Results Although the average of AChE activity in the saliva of people with AD was lower compared to the control group, we found no statistically significant differences using Mann Whitney U test (138 in control group vs. 175 in Alzheimer’s patients, p value=0.25). Additionally, no significant differences were observed in the activity of this enzyme in both sexes or with increased age or duration of the disease. After adjusting for age and gender, there was no association between AChE activity and AD (regression coefficient β=0.08; p value= 0.67). conclusion Saliva AChE activity was not significantly associated with AD. This study might help in introduce a new diagnostic aid for AD or monitor patients with AD. PMID:28274046

  10. The Smad3 linker region contains a transcriptional activation domain.

    PubMed

    Wang, Guannan; Long, Jianyin; Matsuura, Isao; He, Dongming; Liu, Fang

    2005-02-15

    Transforming growth factor-beta (TGF-beta)/Smads regulate a wide variety of biological responses through transcriptional regulation of target genes. Smad3 plays a key role in TGF-beta/Smad-mediated transcriptional responses. Here, we show that the proline-rich linker region of Smad3 contains a transcriptional activation domain. When the linker region is fused to a heterologous DNA-binding domain, it activates transcription. We show that the linker region physically interacts with p300. The adenovirus E1a protein, which binds to p300, inhibits the transcriptional activity of the linker region, and overexpression of p300 can rescue the linker-mediated transcriptional activation. In contrast, an adenovirus E1a mutant, which cannot bind to p300, does not inhibit the linker-mediated transcription. The native Smad3 protein lacking the linker region is unable to mediate TGF-beta transcriptional activation responses, although it can be phosphorylated by the TGF-beta receptor at the C-terminal tail and has a significantly increased ability to form a heteromeric complex with Smad4. We show further that the linker region and the C-terminal domain of Smad3 synergize for transcriptional activation in the presence of TGF-beta. Thus our findings uncover an important function of the Smad3 linker region in Smad-mediated transcriptional control.

  11. Superoxide dismutase, catalase and acetylcholinesterase: biomarkers for the joint effects of cadmium, zinc and methyl parathion contamination in water.

    PubMed

    Ling, XuePing; Zhang, YiHeng; Lu, YingHua; Huang, HeQing

    2011-10-01

    Heavy metals are known to reduce the activities of antioxidant enzymes (e.g. superoxide dismutase, catalase), while organophosphorous insecticides are known to inhibit the activity of the enzyme acetylcholinesterase. In this study, the activities of these three enzymes in zebrafish (Danio rerio) tissues were assessed to evaluate the consequences heavy metal and organophosphate contamination in aquatic systems. When the fish were contacted with water containing a single pollutant, superoxide dismutase activity was affected by the presence of Cd but not by methyl parathion or Zn. However, catalase and acetylcholinesterase activities were sensitive to all three pollutants. The combined treatment showed that the three enzymes could be chosen as biomarkers of joint pollution by both metals and organophosphate. Toxicity tests showed an antagonism interaction between methyl parathion and Cd or Zn, and the change of enzyme activities at 96 hours was in accordance with that.

  12. Crystal Structure of Snake Venom Acetylcholinesterase in Complex with Inhibitory Antibody Fragment Fab410 Bound at the Peripheral Site

    PubMed Central

    Bourne, Yves; Renault, Ludovic; Marchot, Pascale

    2015-01-01

    The acetylcholinesterase found in the venom of Bungarus fasciatus (BfAChE) is produced as a soluble, non-amphiphilic monomer with a canonical catalytic domain but a distinct C terminus compared with the other vertebrate enzymes. Moreover, the peripheral anionic site of BfAChE, a surface site located at the active site gorge entrance, bears two substitutions altering sensitivity to cationic inhibitors. Antibody Elec410, generated against Electrophorus electricus acetylcholinesterase (EeAChE), inhibits EeAChE and BfAChE by binding to their peripheral sites. However, both complexes retain significant residual catalytic activity, suggesting incomplete gorge occlusion by bound antibody and/or high frequency back door opening. To explore a novel acetylcholinesterase species, ascertain the molecular bases of inhibition by Elec410, and document the determinants and mechanisms for back door opening, we solved a 2.7-Å resolution crystal structure of natural BfAChE in complex with antibody fragment Fab410. Crystalline BfAChE forms the canonical dimer found in all acetylcholinesterase structures. Equally represented open and closed states of a back door channel, associated with alternate positions of a tyrosine phenol ring at the active site base, coexist in each subunit. At the BfAChE molecular surface, Fab410 is seated on the long Ω-loop between two N-glycan chains and partially occludes the gorge entrance, a position that fully reflects the available mutagenesis and biochemical data. Experimentally based flexible molecular docking supports a similar Fab410 binding mode onto the EeAChE antigen. These data document the molecular and dynamic peculiarities of BfAChE with high frequency back door opening, and the mode of action of Elec410 as one of the largest peptidic inhibitors targeting the acetylcholinesterase peripheral site. PMID:25411244

  13. Prediction of Active-Region CME Productivity from Magnetograms

    NASA Technical Reports Server (NTRS)

    Falconer, D. A.; Moore, R. L.; Gary, G. A.

    2004-01-01

    We report results of an expanded evaluation of whole-active-region magnetic measures as predictors of active-region coronal mass ejection (CME) productivity. Previously, in a sample of 17 vector magnetograms of 12 bipolar active regions observed by the Marshall Space Flight Center (MSFC) vector magnetograph, from each magnetogram we extracted a measure of the size of the active region (the active region s total magnetic flux a) and four measures of the nonpotentiality of the active region: the strong-shear length L(sub SS), the strong-gradient length L(sub SG), the net vertical electric current I(sub N), and the net-current magnetic twist parameter alpha (sub IN). This sample size allowed us to show that each of the four nonpotentiality measures was statistically significantly correlated with active-region CME productivity in time windows of a few days centered on the day of the magnetogram. We have now added a fifth measure of active-region nonpotentiality (the best-constant-alpha magnetic twist parameter (alpha sub BC)), and have expanded the sample to 36 MSFC vector magnetograms of 31 bipolar active regions. This larger sample allows us to demonstrate statistically significant correlations of each of the five nonpotentiality measures with future CME productivity, in time windows of a few days starting from the day of the magnetogram. The two magnetic twist parameters (alpha (sub 1N) and alpha (sub BC)) are normalized measures of an active region s nonpotentially in that they do not depend directly on the size of the active region, while the other three nonpotentiality measures (L(sub SS), L(sub SG), and I(sub N)) are non-normalized measures in that they do depend directly on active-region size. We find (1) Each of the five nonpotentiality measures is statistically significantly correlated (correlation confidence level greater than 95%) with future CME productivity and has a CME prediction success rate of approximately 80%. (2) None of the nonpotentiality

  14. Observed Helicity of Active Regions in Solar Cycle 21

    NASA Technical Reports Server (NTRS)

    Hagyard, M. J.; Pevtsov, A. A.; Blehm, Z.; Smith, J. E.; Six, Frank (Technical Monitor)

    2003-01-01

    We report the results of a study of helicity in solar active regions during the peak of activity in solar cycle 21 from observations with the Marshall Space Flight Center's solar vector magnetograph. Using the force-free parameter alpha as the proxy for helicity, we calculated an average value of alpha for each of 60 active regions from a total of 449 vector magnetograms that were obtained during the period 1980 March to November. The signs of these average values of alpha were correlated with the latitude of the active regions to test the hemispheric rule of helicity that has been proposed for solar magnetic fields: negative helicity predominant in northern latitudes, positive in the southern ones. We have found that of the 60 regions that were observed, 30 obey the hemispheric rule and 30 do not.

  15. Photospheric Magnetic Free Energy Density of Solar Active Regions

    NASA Astrophysics Data System (ADS)

    Zhang, Hongqi

    2016-12-01

    We present the photospheric energy density of magnetic fields in two solar active regions (one of them recurrent) inferred from observational vector magnetograms, and compare it with other available differently defined energy parameters of magnetic fields in the photosphere. We analyze the magnetic fields in Active Regions NOAA 6580-6619-6659 and 11158. The quantity 1/4π{B}n\\cdot{B}p is an important energy parameter that reflects the contribution of magnetic shear to the difference between the potential (Bp) and the non-potential magnetic field (Bn), and also the contribution to the free magnetic energy near the magnetic neutral lines in the active regions. It is found that the photospheric mean magnetic energy density shows clear changes before the powerful solar flares in Active Region NOAA 11158, which is consistent with the change in magnetic fields in the flaring lower atmosphere.

  16. AFS dynamics in a short-lived active region

    NASA Astrophysics Data System (ADS)

    Zuccarello, F.; Battiato, V.; Contarino, L.; Romano, P.; Spadaro, D.; Vlahos, L.

    2005-11-01

    In the framework of the study on active region emergence, we report the results obtained from the analysis of the short-lived (7 days) active region NOAA 10407. The data used were acquired during an observational campaign carried out with the THEMIS telescope in IPM mode in July 2003, coordinated with other ground- and space-based instruments (INAF-OACT, DOT, BBSO, MDI/SOHO, EIT/SOHO, TRACE). We determined the morphological and magnetic evolution of NOAA 10407, as well as the velocity fields associated with its magnetic structures. Within the limits imposed by the spatial and temporal resolution of the images analyzed, the first evidence of the active region formation is initially observed in the transition region and lower corona, and later on (i.e. after about 7 h) in the inner layers, as found in a previous analysis concerning a long-lived, recurrent active region. The results also indicate that the AFS formed in the active region shows typical upward motion at the AFS's tops and downward motion at the footpoints. The velocity values relevant to the upward motions decrease over the evolution of the region, similarly to the case of the recurrent active region, while we notice an increasing trend in the downflow velocity during the early phases of the time interval analyzed by THEMIS. On the other hand, the AFS preceding legs show a higher downflow than the following ones, a result in contrast with that found in the long-lived active region. The chromospheric area overhanging the sunspot umbra shows an upward motion of ˜ 2 km s-1, while that above the pores shows a downward motion of ~4 km s-1.

  17. Are soluble and membrane-bound rat brain acetylcholinesterase different

    SciTech Connect

    Andres, C.; el Mourabit, M.; Stutz, C.; Mark, J.; Waksman, A. )

    1990-11-01

    Salt-soluble and detergent-soluble acetylcholinesterases (AChE) from adult rat brain were purified to homogeneity and studied with the aim to establish the differences existing between these two forms. It was found that the enzymatic activities of the purified salt-soluble AChE as well as the detergent-soluble AChE were dependent on the Triton X-100 concentration. Moreover, the interaction of salt-soluble AChE with liposomes suggests amphiphilic behaviour of this enzyme. Serum cholinesterase (ChE) did not bind to liposomes but its activity was also detergent-dependent. Detergent-soluble AChE remained in solution below critical micellar concentrations of Triton X-100. SDS polyacrylamide gel electrophoresis of purified, Biobeads-treated and iodinated detergent-soluble 11 S AChE showed, under non reducing conditions, bands of 69 kD, 130 kD and greater than 250 kD corresponding, respectively, to monomers, dimers and probably tetramers of the same polypeptide chain. Under reducing conditions, only a 69 kD band was detected. It is proposed that an amphiphilic environment stabilizes the salt-soluble forms of AChE in the brain in vivo and that detergent-soluble Biobeads-treated 11 S AChE possess hydrophobic domain(s) different from the 20 kD peptide already described.

  18. Acetylcholinesterase inhibition within the lycorine series of Amaryllidaceae alkaloids.

    PubMed

    Nair, Jerald J; van Staden, Johannes

    2012-07-01

    The plant family Amaryllidaceae occupies a privileged status within the botanical hierarchy due to its horticultural and ornamental appeal, as well as its widespread usage in the traditional medicinal practices of indigenous peoples across the globe. Of greater significance are the unique, structurally-diverse alkaloid constituents produced by members of the family, which has spawned several biologically significant molecules. In this regard, the Alzheimer's drug galanthamine has gained much prominence due to its selective and reversible inhibitory interaction with the enzyme acetylcholinesterase (AChE), of significance in the progression of neurodegeneration associated with Alzheimer's disease (AD). The lycorine series of compounds within the family have recently emerged as novel inhibitors of AChE, in some instances with higher levels of activity compared with the commercial drug galanthamine, making them attractive targets for natural product and synthetically-driven structure-activity relationship studies. This brief survey traces the emergence of lycorine compounds over the past decade as promising leads in the therapeutic approach towards AD and their possible future advancement onto the clinical stage.

  19. THE COLD SHOULDER: EMISSION MEASURE DISTRIBUTIONS OF ACTIVE REGION CORES

    SciTech Connect

    Schmelz, J. T.; Pathak, S.

    2012-09-10

    The coronal heating mechanism for active region core loops is difficult to determine because these loops are often not resolved and cannot be studied individually. Rather, we concentrate on the 'inter-moss' areas between loop footpoints. We use observations from the Hinode EUV Imaging Spectrometer and the X-Ray Telescope to calculate the emission measure distributions of eight inter-moss areas in five different active regions. The combined data sets provide both high- and low-temperature constraints and ensure complete coverage in the temperature range appropriate for active regions. For AR 11113, the emission can be modeled with heating events that occur on timescales less than the cooling time. The loops in the core regions appear to be close to equilibrium and are consistent with steady heating. The other regions studied, however, appear to be dominated by nanoflare heating. Our results are consistent with the idea that active region age is an important parameter in determining whether steady or nanoflare heating is primarily responsible for the core emission, that is, older regions are more likely to be dominated by steady heating, while younger regions show more evidence of nanoflares.

  20. Active Ageing Level of Older Persons: Regional Comparison in Thailand

    PubMed Central

    Haque, Md. Nuruzzaman

    2016-01-01

    Active ageing level and its discrepancy in different regions (Bangkok, Central, North, Northeast, and South) of Thailand have been examined for prioritizing the policy agenda to be implemented. Attempt has been made to test preliminary active ageing models for Thai older persons and hence active ageing index (AAI, ranges from 0 to 1) has been estimated. Using nationally representative data and confirmatory factor analysis approach, this study justified active ageing models for female and male older persons in Thailand. Results revealed that active ageing level of Thai older persons is not high (mean AAIs for female and male older persons are 0.64 and 0.61, resp., and those are significantly different (p < 0.001)). Mean AAI in Central region is lower than North, Northeast, and South regions but there is no significant difference in the latter three regions of Thailand. Special emphasis should be given to Central region and policy should be undertaken for increasing active ageing level. Implementation of an Integrated Active Ageing Package (IAAP), containing policies for older persons to improve their health and economic security, to promote participation in social groups and longer working lives, and to arrange learning programs, would be helpful for increasing older persons' active ageing level in Thailand. PMID:27375903

  1. DISTRIBUTION OF ELECTRIC CURRENTS IN SOLAR ACTIVE REGIONS

    SciTech Connect

    Török, T.; Titov, V. S.; Mikić, Z.; Leake, J. E.; Archontis, V.; Linton, M. G.; Dalmasse, K.; Aulanier, G.; Kliem, B.

    2014-02-10

    There has been a long-standing debate on the question of whether or not electric currents in solar active regions are neutralized. That is, whether or not the main (or direct) coronal currents connecting the active region polarities are surrounded by shielding (or return) currents of equal total value and opposite direction. Both theory and observations are not yet fully conclusive regarding this question, and numerical simulations have, surprisingly, barely been used to address it. Here we quantify the evolution of electric currents during the formation of a bipolar active region by considering a three-dimensional magnetohydrodynamic simulation of the emergence of a sub-photospheric, current-neutralized magnetic flux rope into the solar atmosphere. We find that a strong deviation from current neutralization develops simultaneously with the onset of significant flux emergence into the corona, accompanied by the development of substantial magnetic shear along the active region's polarity inversion line. After the region has formed and flux emergence has ceased, the strong magnetic fields in the region's center are connected solely by direct currents, and the total direct current is several times larger than the total return current. These results suggest that active regions, the main sources of coronal mass ejections and flares, are born with substantial net currents, in agreement with recent observations. Furthermore, they support eruption models that employ pre-eruption magnetic fields containing such currents.

  2. Photospheric Magnetic Diffusion by Measuring Moments of Active Regions

    NASA Astrophysics Data System (ADS)

    Engell, Alexander; Longcope, D.

    2013-07-01

    Photospheric magnetic surface diffusion is an important constraint for the solar dynamo. The HMI Active Region Patches (HARPs) program automatically identify all magnetic regions above a certain flux. In our study we measure the moments of ARs that are no longer actively emerging and can thereby give us good statistical constraints on photospheric diffusion. We also present the diffusion properties as a function of latitude, flux density, and single polarity (leading or following) within each HARP.

  3. Solar Irradiance Variations on Active Region Time Scales

    NASA Technical Reports Server (NTRS)

    Labonte, B. J. (Editor); Chapman, G. A. (Editor); Hudson, H. S. (Editor); Willson, R. C. (Editor)

    1984-01-01

    The variations of the total solar irradiance is an important tool for studying the Sun, thanks to the development of very precise sensors such as the ACRIM instrument on board the Solar Maximum Mission. The largest variations of the total irradiance occur on time scales of a few days are caused by solar active regions, especially sunspots. Efforts were made to describe the active region effects on total and spectral irradiance.

  4. The nature of chromospheric active regions on V410 Tauri

    NASA Astrophysics Data System (ADS)

    Mekkaden, M. V.; Pukalenthi, S.; Muneer, S.; Bastian, Anju Barbara

    2005-12-01

    We present spectroscopic observations in the region of H alpha and Li I lines of the weak emission T Tauri star V410 Tau obtained over 1999/2000, 2002/2003 and 2003/2004 seasons. The emission strength showed rotational modulation during the 1999/2000 season in such a way that the emis- sion strength is maximum at light minimum and vice versa. This indicates that the photospheric and chromospheric active regions overlap over shorter dura- tions of time and the lifetimes of chromospheric active regions are far shorter than the photospheric active regions. But the observations obtained during the 2003/2004 season do not follow the trend observed at earlier seasons. This can be due to the change in the location of chromospheric active regions. Another possibility is the occurrence of a major change in the photospheric active re- gions that have caused a redistribution of photospheric as well as chromospheric active regions. The Li I EW does not show any appreciable change over the four-year period.

  5. A point mutation in the acetylcholinesterase-1 gene is associated with chlorpyrifos resistance in the plant bug Apolygus lucorum.

    PubMed

    Wu, Shuwen; Zuo, Kairan; Kang, Zhaokui; Yang, Yihua; Oakeshott, John G; Wu, Yidong

    2015-10-01

    Control of Chinese Apolygus lucorum relies heavily on organophosphate insecticides. Here we describe resistance to the organophosphate chlorpyrifos in an A. lucorum strain, BZ-R, which was developed from a field-collected strain (BZ) by selection with chlorpyrifos in the laboratory. BZ-R showed 21-58 fold resistance to chlorpyrifos compared with the laboratory reference strain LSF and another susceptible strain, BZ-S, derived from BZ. BZ-R also showed several fold resistance to two other organophosphates and a carbamate. No synergism of chlorpyrifos by metabolic enzyme inhibitors nor any increase in detoxifying enzyme activities were observed in BZ-R. No sequence differences in acetylcholinesterase-2 were found to be associated with the resistance but the frequency of an alanine to serine substitution at position 216 of acetylcholinesterase-1 was 100% in BZ-R, ∼21-23% in SLF and BZ, and 0% in BZ-S. A single generation treatment of chlorpyrifos on the BZ strain also increased its frequency of the serine substitution to 64%. Recombinantly expressed acetylcholinesterase-1 carrying the serine substitution was about five fold less sensitive to inhibition by chlorpyrifos oxon than the wild-type enzyme. Quantitative real-time PCR found no differences in ace1 or ace2 expression levels among the strains tested. Thus the chlorpyrifos resistance is strongly associated with the serine substituted acetylcholinesterase-1. An equivalent substitution has been found to confer resistance to many organophosphate and carbamate insecticides in four other insect species.

  6. Twist of Magnetic Fields in Solar Active Regions

    NASA Astrophysics Data System (ADS)

    Zhang, Hongqi; Bao, Shudong; Kuzanyan, Kirill M.

    2002-05-01

    We study the twist properties of photospheric magnetic fields in solar active regions using magnetographic data on 422 active regions obtained at the Huairou Solar Observing Station in 1988 1997. We calculate the mean twist (force-free field αf) of the active regions and compare it with the mean current-helicity density of these same active regions, h c =B ∥·(∇×B)∥. The latitude and longitude distributions and time dependence of these quantities is analyzed. These parameters represent two different tracers of the α effect in dynamo theory, so we might expect them to possess similar properties. However, apart from differences in their definitions, they also display differences associated with the technique used to recalculate the magnetographic data and with their different physical meanings. The distributions of the mean αf and h c both show hemispherical asymmetry—negative (positive) values in the northern (southern) hemisphere—although this tendency is stronger for h c. One reason for these differences may be the averaging procedure, when twists of opposite sign in regions with weak fields make a small contribution to the mean current-helicity density. Such transequatorial regularity is in agreement with the expectations of dynamo theory. In some active regions, the average αf and h c do not obey this transequatorial rule. As a whole, the mean twist of the magnetic fields αf of active regions does not vary significantly with the solar cycle. Active regions that do not follow the general behavior for αf do not show any appreciable tendency to cluster at certain longitudes, in contrast to results for h c noted in previous studies. We analyze similarities and differences in the distributions of these two quantities. We conclude that using only one of these tracers, such as αf, to search for signatures of the α effect can have disadvantages, which should be taken into account in future studies.

  7. SDO/HMI survey of emerging active regions for helioseismology

    NASA Astrophysics Data System (ADS)

    Schunker, H.; Braun, D. C.; Birch, A. C.; Burston, R. B.; Gizon, L.

    2016-11-01

    Context. Observations from the Solar Dynamics Observatory (SDO) have the potential for allowing the helioseismic study of the formation of hundreds of active regions, which would enable us to perform statistical analyses. Aims: Our goal is to collate a uniform data set of emerging active regions observed by the SDO/HMI instrument suitable for helioseismic analysis, where each active region is centred on a 60° × 60° area and can be observed up to seven days before emergence. Methods: We restricted the sample to active regions that were visible in the continuum and emerged into quiet Sun largely avoiding pre-existing magnetic regions. As a reference data set we paired a control region (CR), with the same latitude and distance from central meridian, with each emerging active region (EAR). The control regions do not have any strong emerging flux within 10° of the centre of the map. Each region was tracked at the Carrington rotation rate as it crossed the solar disk, within approximately 65° from the central meridian and up to seven days before, and seven days after, emergence. The mapped and tracked data, consisting of line-of-sight velocity, line-of-sight magnetic field, and intensity as observed by SDO/HMI, are stored in datacubes that are 410 min in duration and spaced 320 min apart. We call this data set, which is currently comprised of 105 emerging active regions observed between May 2010 and November 2012, the SDO Helioseismic Emerging Active Region (SDO/HEAR) survey. Results: To demonstrate the utility of a data set of a large number of emerging active regions, we measure the relative east-west velocity of the leading and trailing polarities from the line-of-sight magnetogram maps during the first day after emergence. The latitudinally averaged line-of-sight magnetic field of all the EARs shows that, on average, the leading (trailing) polarity moves in a prograde (retrograde) direction with a speed of 121 ± 22 m s-1 (-70 ± 13 m s-1) relative to the

  8. Earth resources-regional transfer activity contracts review

    NASA Technical Reports Server (NTRS)

    Bensko, J., Jr.; Daniels, J. L.; Downs, S. W., Jr.; Jones, N. L.; Morton, R. R.; Paludan, C. T.

    1977-01-01

    A regional transfer activity contracts review held by the Earth Resources Office was summarized. Contracts in the earth resources field primarily directed toward applications of satellite data and technology in solution of state and regional problems were reviewed. A summary of the progress of each contract was given in order to share experiences of researchers across a seven state region. The region included Missouri, Kentucky, Tennessee, Mississippi, Alabama, Georgia, and North Carolina. Research in several earth science disciplines included forestry, limnology, water resources, land use, geology, and mathematical modeling. The use of computers for establishment of information retrieval systems was also emphasized.

  9. Predictions of active region flaring probability using subsurface helicity measurements

    NASA Astrophysics Data System (ADS)

    Reinard, A. A.; Komm, R.; Hill, F.

    2010-12-01

    Solar flares are responsible for a number of hazardous effects on the earth such as disabling high-frequency radio communications, interfering with GPS measurements, and disrupting satellites. However, forecasting flare occurrence is currently very difficult. One possible means for predicting flare occurrence lies in helioseismology, i.e. analysis of the region below the active region for signs of an impending flare. Time series helioseismic data collected by the Global Oscillation Network Group (GONG) has been analyzed for a subset of active regions that produce large flares and a subset with very high magnetic field strength that produce no flares. A predictive parameter has been developed and analyzed using discriminant analysis as well as traditional forecasting tools such as the Heidke skill score. Preliminary results show that this parameter predicts the flaring probability of an active region 2-3 days in advance with a relatively high degree of success.

  10. Helium Line Formation and Abundance in a Solar Active Region

    NASA Astrophysics Data System (ADS)

    Mauas, P. J. D.; Andretta, V.; Falchi, A.; Falciani, R.; Teriaca, L.; Cauzzi, G.

    2005-01-01

    An observing campaign (SOHO JOP 139), coordinated between ground-based and Solar and Heliospheric Observatory (SOHO) instruments, has been planned to obtain simultaneous spectroheliograms of the same active region in several spectral lines. The chromospheric lines Ca II K, Hα, and Na I D, as well as He I 10830, 5876, 584, and He II 304 Å lines have been observed. The EUV radiation in the range λ<500 Å and in the range 260<λ<340 Å has also been measured at the same time. These simultaneous observations allow us to build semiempirical models of the chromosphere and low transition region of an active region, taking into account the estimated total number of photoionizing photons impinging on the target active region and their spectral distribution. We obtained a model that matches very well all the observed line profiles, using a standard value for the He abundance ([He]=0.1) and a modified distribution of microturbulence. For this model we study the influence of the coronal radiation on the computed helium lines. We find that, even in an active region, the incident coronal radiation has a limited effect on the UV He lines, while it is of fundamental importance for the D3 and 10830 Å lines. Finally, we build two more models, assuming values of He abundance [He]=0.07 and 1.5, only in the region where temperatures are >1×104 K. This region, between the chromosphere and transition region, has been indicated as a good candidate for processes that might be responsible for strong variations of [He]. The set of our observables can still be well reproduced in both cases, changing the atmospheric structure mainly in the low transition region. This implies that, to choose between different values of [He], it is necessary to constrain the transition region with different observables, independent of the He lines.

  11. Universities and Economic Development Activities: A UK Regional Comparison

    ERIC Educational Resources Information Center

    Decter, Moira; Cave, Frank; Rose, Mary; Peers, Gill; Fogg, Helen; Smith, Susan M.

    2011-01-01

    A number of UK universities prioritize economic development or regeneration activities and for some of these universities such activities are the main focus of their knowledge transfer work. This study compares two regions of the UK--the North West and the South East of England--which have very different levels of economic performance.…

  12. IFLA General Conference, 1985. Division on Regional Activities. Papers.

    ERIC Educational Resources Information Center

    International Federation of Library Associations, The Hague (Netherlands).

    Papers on regional library activities which were presented at the 1985 International Federation of Library Associations (IFLA) conference include: (1) "Importance of Information Resources in National Development with Particular Reference to the Asian Scene" (Yogendra P. Dubey, India); (2) "Report of the Activities of the Regional…

  13. A novel role for synaptic acetylcholinesterase as an apoptotic deoxyribonuclease

    PubMed Central

    Du, Aiying; Xie, Jing; Guo, Kaijie; Yang, Lei; Wan, Yihan; OuYang, Qi; Zhang, Xuejin; Niu, Xin; Lu, Lu; Wu, Jun; Zhang, Xuejun

    2015-01-01

    In addition to terminating neurotransmission by hydrolyzing acetylcholine, synaptic acetylcholinesterase (AChES) has been found to have a pro-apoptotic role. However, the underlying mechanism has rarely been investigated. Here, we report a nuclear translocation-dependent role for AChES as an apoptotic deoxyribonuclease (DNase). AChES polypeptide binds to and cleaves naked DNA at physiological pH in a Ca2+–Mg2+-dependent manner. It also cleaves chromosomal DNA both in pre-fixed and in apoptotic cells. In the presence of a pan-caspase inhibitor, the cleavage still occurred after nuclear translocation of AChES, implying that AChES-DNase acts in a CAD- and EndoG-independent manner. AChE gene knockout impairs apoptotic DNA cleavage; this impairment is rescued by overexpression of the wild-type but not (aa 32–138)-deleted AChES. Furthermore, in comparison with the nuclear-localized wild-type AChES, (aa 32–138)-deleted AChES loses the capacity to initiate apoptosis. These observations confirm that AChES mediates apoptosis via its DNase activity. PMID:27462404

  14. Amyloid-β-Acetylcholinesterase complexes potentiate neurodegenerative changes induced by the Aβ peptide. Implications for the pathogenesis of Alzheimer's disease

    PubMed Central

    2010-01-01

    The presence of amyloid-β (Aβ) deposits in selected brain regions is a hallmark of Alzheimer's disease (AD). The amyloid deposits have "chaperone molecules" which play critical roles in amyloid formation and toxicity. We report here that treatment of rat hippocampal neurons with Aβ-acetylcholinesterase (Aβ-AChE) complexes induced neurite network dystrophia and apoptosis. Moreover, the Aβ-AChE complexes induced a sustained increase in intracellular Ca2+ as well as a loss of mitochondrial membrane potential. The Aβ-AChE oligomers complex also induced higher alteration of Ca2+ homeostasis compared with Aβ-AChE fibrillar complexes. These alterations in calcium homeostasis were reversed when the neurons were treated previously with lithium, a GSK-3β inhibitor; Wnt-7a ligand, an activator for Wnt Pathway; and an N-methyl-D-aspartate (NMDA) receptor antagonist (MK-801), demonstrating protective roles for activation of the Wnt signaling pathway as well as for NMDA-receptor inhibition. Our results indicate that the Aβ-AChE complexes enhance Aβ-dependent deregulation of intracellular Ca2+ as well as mitochondrial dysfunction in hippocampal neurons, triggering an enhanced damage than Aβ alone. From a therapeutic point of view, activation of the Wnt signaling pathway, as well as NMDAR inhibition may be important factors to protect neurons under Aβ-AChE attack. PMID:20205793

  15. Activated region fitting: a robust high-power method for fMRI analysis using parameterized regions of activation.

    PubMed

    Weeda, Wouter D; Waldorp, Lourens J; Christoffels, Ingrid; Huizenga, Hilde M

    2009-08-01

    An important issue in the analysis of fMRI is how to account for the spatial smoothness of activated regions. In this article a method is proposed to accomplish this by modeling activated regions with Gaussian shapes. Hypothesis tests on the location, spatial extent, and amplitude of these regions are performed instead of hypothesis tests of individual voxels. This increases power and eases interpretation. Simulation studies show robust hypothesis tests under misspecification of the shape model, and increased power over standard techniques especially at low signal-to-noise ratios. An application to real single-subject data also indicates that the method has increased power over standard methods.

  16. Dynamics of active regions observed with Hinode XRT

    NASA Astrophysics Data System (ADS)

    Sakao, Taro

    We present dynamics of active regions observed with the X-Ray Telescope (XRT) aboard Hinode. XRT is a grazing-incidence imager with a Walter Type-I-like mirror of 34 cm diameter with a back-illuminated CCD device. The XRT can image the X-ray corona of the Sun with angular resolution consistent with 1 arcsec CCD pixel size. In addition to this unprecedentedly-high angular resolution ever achieved as a solar X-ray telescope, enhanced sensitivity of the CCD towards longer X-ray wavelengths (particularly beyond 50 Angstroms) enables XRT to image, and perform temperature diagnostics on, a wide range of coronal plasmas from those as low as 1 MK to high-temperature plasmas even exceeding 10 MK. This adds a notable advantage to the XRT such that it can observe most, if not all, active phenomena taking place in and around active regions. Since the beginning of observations with XRT on 23 October 2006, the XRT has so far made various interesting observations regarding active regions. These include (1) continuous outflow of plasmas from the edge of a solar active region that is likely to be a source of (slow) solar wind, (2) clear signature of eruptions for activities even down to GOES B-level, (3) detailed structure and evolution of flaring loops, (4) formation of large-scale hot loops around active regions, and so on. Dynamic phenomena in and around active regions observed with Hinode XRT will be presented and their possible implications to the Sun-Earth connection investigation will be discussed.

  17. EVIDENCE OF IMPULSIVE HEATING IN ACTIVE REGION CORE LOOPS

    SciTech Connect

    Tripathi, Durgesh; Mason, Helen E.; Klimchuk, James A.

    2010-11-01

    Using a full spectral scan of an active region from the Extreme-Ultraviolet Imaging Spectrometer (EIS) we have obtained emission measure EM(T) distributions in two different moss regions within the same active region. We have compared these with theoretical transition region EMs derived for three limiting cases, namely, static equilibrium, strong condensation, and strong evaporation from Klimchuk et al. The EM distributions in both the moss regions are strikingly similar and show a monotonically increasing trend from log T[K] = 5.15-6.3. Using photospheric abundances, we obtain a consistent EM distribution for all ions. Comparing the observed and theoretical EM distributions, we find that the observed EM distribution is best explained by the strong condensation case (EM{sub con}), suggesting that a downward enthalpy flux plays an important and possibly dominant role in powering the transition region moss emission. The downflows could be due to unresolved coronal plasma that is cooling and draining after having been impulsively heated. This supports the idea that the hot loops (with temperatures of 3-5 MK) seen in the core of active regions are heated by nanoflares.

  18. Mutations in Acetylcholinesterase2 (ace2) increase the insensitivity of acetylcholinesterase to fosthiazate in the root-knot nematode Meloidogyne incognita.

    PubMed

    Huang, Wen-Kun; Wu, Qin-Song; Peng, Huan; Kong, Ling-An; Liu, Shi-Ming; Yin, Hua-Qun; Cui, Ru-Qiang; Zhan, Li-Ping; Cui, Jiang-Kuan; Peng, De-Liang

    2016-11-29

    The root-knot nematode Meloidogyne incognita causes severe damage to continuously cropping vegetables. The control of this nematode relies heavily on organophosphate nematicides in China. Here, we described resistance to the organophosphate nematicide fosthiazate in a greenhouse-collected resistant population (RP) and a laboratory susceptible population (SP) of M. incognita. Fosthiazate was 2.74-fold less toxic to nematodes from RP than that from SP. Quantitative real-time PCR revealed that the acetylcholinesterase2 (ace2) transcription level in the RP was significantly higher than that in the SP. Eighteen nonsynonymous amino acid differences in ace2 were observed between the cDNA fragments of the RP and SP. The acetylcholinesterase (AChE) protein activity in the RP was significantly reduced compared with that in the SP. After knocking down the ace2 gene, the ace2 transcription level was significantly decreased, but no negative impact on the infection of juveniles was observed. The 50% lethal concentration of the RNAi RP population decreased 40%, but the inhibition rate of fosthiazate against AChE activity was significantly increased in RP population. Thus, the increased fosthiazate insensitivity in the M. incognita resistant population was strongly associated with mutations in ace2. These results provide valuable insights into the resistance mechanism of root-knot nematode to organophosphate nematicides.

  19. Mutations in Acetylcholinesterase2 (ace2) increase the insensitivity of acetylcholinesterase to fosthiazate in the root-knot nematode Meloidogyne incognita

    PubMed Central

    Huang, Wen-Kun; Wu, Qin-Song; Peng, Huan; Kong, Ling-An; Liu, Shi-Ming; Yin, Hua-Qun; Cui, Ru-Qiang; Zhan, Li-Ping; Cui, Jiang-Kuan; Peng, De-Liang

    2016-01-01

    The root-knot nematode Meloidogyne incognita causes severe damage to continuously cropping vegetables. The control of this nematode relies heavily on organophosphate nematicides in China. Here, we described resistance to the organophosphate nematicide fosthiazate in a greenhouse-collected resistant population (RP) and a laboratory susceptible population (SP) of M. incognita. Fosthiazate was 2.74-fold less toxic to nematodes from RP than that from SP. Quantitative real-time PCR revealed that the acetylcholinesterase2 (ace2) transcription level in the RP was significantly higher than that in the SP. Eighteen nonsynonymous amino acid differences in ace2 were observed between the cDNA fragments of the RP and SP. The acetylcholinesterase (AChE) protein activity in the RP was significantly reduced compared with that in the SP. After knocking down the ace2 gene, the ace2 transcription level was significantly decreased, but no negative impact on the infection of juveniles was observed. The 50% lethal concentration of the RNAi RP population decreased 40%, but the inhibition rate of fosthiazate against AChE activity was significantly increased in RP population. Thus, the increased fosthiazate insensitivity in the M. incognita resistant population was strongly associated with mutations in ace2. These results provide valuable insights into the resistance mechanism of root-knot nematode to organophosphate nematicides. PMID:27897265

  20. Eruptions that Drive Coronal Jets in a Solar Active Region

    NASA Technical Reports Server (NTRS)

    Sterling, Alphonse C.; Moore, Ronald L.; Falconer, David A.; Panesar, Navdeep K.; Akiyama, Sachiko; Yashiro, Seiji; Gopalswamy, Nat

    2016-01-01

    Solar coronal jets are common in both coronal holes and in active regions (e.g., Shibata et al. 1992, Shimojo et al. 1996, Cirtain et al. 2007. Savcheva et al. 2007). Recently, Sterling et al. (2015), using data from Hinode/XRT and SDO/AIA, found that coronal jets originating in polar coronal holes result from the eruption of small-scale filaments (minifilaments). The jet bright point (JBP) seen in X-rays and hotter EUV channels off to one side of the base of the jet's spire develops at the location where the minifilament erupts, consistent with the JBPs being miniature versions of typical solar flares that occur in the wake of large-scale filament eruptions. Here we consider whether active region coronal jets also result from the same minifilament-eruption mechanism, or whether they instead result from a different mechanism (e.g. Yokoyama & Shibata 1995). We present observations of an on-disk active region (NOAA AR 11513) that produced numerous jets on 2012 June 30, using data from SDO/AIA and HMI, and from GOES/SXI. We find that several of these active region jets also originate with eruptions of miniature filaments (size scale 20'') emanating from small-scale magnetic neutral lines of the region. This demonstrates that active region coronal jets are indeed frequently driven by minifilament eruptions. Other jets from the active region were also consistent with their drivers being minifilament eruptions, but we could not confirm this because the onsets of those jets were hidden from our view. This work was supported by funding from NASA/LWS, NASA/HGI, and Hinode. A full report of this study appears in Sterling et al. (2016).

  1. Effects of harmine, an acetylcholinesterase inhibitor, on spatial learning and memory of APP/PS1 transgenic mice and scopolamine-induced memory impairment mice.

    PubMed

    He, Dandan; Wu, Hui; Wei, Yue; Liu, Wei; Huang, Fei; Shi, Hailian; Zhang, Beibei; Wu, Xiaojun; Wang, Changhong

    2015-12-05

    Harmine, a β-carboline alkaloid present in Peganum harmala with a wide spectrum of pharmacological activities, has been shown to exert strong inhibition against acetylcholinesterase in vitro. However, whether it can rescue the impaired cognition has not been elucidated yet. In current study, we examined its effects on scopolamine-induced memory impairment mice and APP/PS1 transgenic mice, one of the models for Alzheimer's disease, using Morris Water Maze test. In addition, whether harmine could penetrate blood brain barrier, interact with and inhibit acetylcholinesterase, and activate downstream signaling network was also investigated. Our results showed that harmine (20mg/kg) administered by oral gavage for 2 weeks could effectively enhance the spatial cognition of C57BL/6 mice impaired by intraperitoneal injection of scopolamine (1mg/kg). Meanwhile, long-term consumption of harmine (20mg/kg) for 10 weeks also slightly benefited the impaired memory of APP/PS1 mice. Furthermore, harmine could pass through blood brain barrier, penetrate into the brain parenchyma shortly after oral administration, and modulate the expression of Egr-1, c-Jun and c-Fos. Molecular docking assay disclosed that harmine molecule could directly dock into the catalytic active site of acetylcholinesterase, which was partially confirmed by its in vivo inhibitory activity on acetylcholinesterase. Taken together, all these results suggested that harmine could ameliorate impaired memory by enhancement of cholinergic neurotransmission via inhibiting the activity of acetylcholinesterase, which may contribute to its clinical use in the therapy of neurological diseases characterized with acetylcholinesterase deficiency.

  2. Interplanetary planar magnetic structures associated with expanding active regions

    NASA Technical Reports Server (NTRS)

    Nakagawa, Tomoko; Uchida, Yutaka

    1995-01-01

    Planar magnetic structures are interplanetary objects whose magnetic field cannot be explained by Parker's solar wind model. They are characterized by two-dimensional structure of magnetic field that are highly variable and parallel to a plane which is inclined to the ecliptic plane. They appeared independently of interplanetary compression, solar flares, active prominences nor filament disappearances, but the sources often coincided with active regions. On the other hand, it has been discovered by the Yohkoh Soft X-ray telescope that active-region corona expand outwards at speeds of a few to a few tens of km/s near the Sun. The expansions occurred repeatedly, almost continually, even in the absence of any sizable flares. In the Yohkoh Soft X-ray images, the active-region corona seems to expand out into interplanetary space. Solar sources of interplanetary planar magnetic structures observed by Sakigake were examined by Yohkoh soft X-ray telescope. During a quiet period of the Sun from January 6 to November 11, 1993, there found 5 planar magnetic structures according to the criteria (absolute value of Bn)/(absolute value of B) less than 0.1 for planarity and (dB)/(absolute value of B) greater than 0.7 for variability of magnetic field, where Bn, dB, and the absolute value of B are field component normal to a plane, standard deviation, and average of the magnitude of the magnetic field, respectively. Sources of 4 events were on low-latitude (less than 5 degrees) active regions from which loop-like structures were expanding. The coincidence, 80%, is extremely high with respect to accidental coincidence, 7%, of Sakigake windows of solar wind observation with active regions. The last source was on loop-like features which seemed to be related with a mid-latitude (20 degrees) active region.

  3. Bimanual passive movement: functional activation and inter-regional coupling.

    PubMed

    Macaluso, Emiliano; Cherubini, Andrea; Sabatini, Umberto

    2007-01-01

    The aim of this study was to investigate intra-regional activation and inter-regional connectivity during passive movement. During fMRI, a mechanic device was used to move the subject's index and middle fingers. We assessed four movement conditions (unimanual left/right, bimanual symmetric/asymmetric), plus Rest. A conventional intra-regional analysis identified the passive stimulation network, including motor cortex, primary and secondary somatosensory cortex, plus the cerebellum. The posterior (sensory) part of the sensory-motor activation around the central sulcus showed a significant modulation according to the symmetry of the bimanual movement, with greater activation for asymmetric compared to symmetric movements. A second set of fMRI analyses assessed condition-dependent changes of coupling between sensory-motor regions around the superior central sulcus and the rest of the brain. These analyses showed a high inter-regional covariation within the entire network activated by passive movement. However, the specific experimental conditions modulated these patterns of connectivity. Highest coupling was observed during the Rest condition, and the coupling between homologous sensory-motor regions around the left and right central sulcus was higher in bimanual than unimanual conditions. These findings demonstrate that passive movement can affect the connectivity within the sensory-motor network. We conclude that implicit detection of asymmetry during bimanual movement relies on associative somatosensory region in post-central areas, and that passive stimulation reduces the functional connectivity within the passive movement network. Our findings open the possibility to combine passive movement and inter-regional connectivity as a tool to investigate the functionality of the sensory-motor system in patients with very poor mobility.

  4. TARPs: Tracked Active Region Patches from SoHO/MDI

    NASA Astrophysics Data System (ADS)

    Turmon, M.; Hoeksema, J. T.; Bobra, M.

    2013-12-01

    We describe progress toward creating a retrospective MDI data product consisting of tracked magnetic features on the scale of solar active regions, abbreviated TARPs (Tracked Active Region Patches). The TARPs are being developed as a backward-looking extension (covering approximately 3500 regions spanning 1996-2010) to the HARP (HMI Active Region Patch) data product that has already been released for HMI (2010-present). Like the HARPs, the MDI TARP data set is designed to be a catalog of active regions (ARs), indexed by a region ID number, analogous to a NOAA AR number, and time. TARPs from MDI are computed based on the 96-minute synoptic magnetograms and pseudo-continuum intensitygrams. As with the related HARP data product, the approximate threshold for significance is 100G. Use of both image types together allows faculae and sunspots to be separated out as sub-classes of activity, in addition to identifying the overall active region that the faculae/sunspots are part of. After being identified in single images, the magnetically-active patches are grouped and tracked from image to image. Merges among growing active regions, as well as faint active regions hovering at the threshold of detection, are handled automatically. Regions are tracked from their inception until they decay within view, or transit off the visible disk. The final data product is indexed by a nominal AR number and time. For each active region and for each time, a bitmap image is stored containing the precise outline of the active region. Additionaly, metadata such as areas and integrated fluxes are stored for each AR and for each time. Because there is a calibration between the HMI and MDI magnetograms (Liu, Hoeksema et al. 2012), it is straightforward to use the same classification and tracking rules for the HARPs (from HMI) and the MDI TARPs. We anticipate that this will allow a consistent catalog spanning both instruments. We envision several uses for the TARP data product, which will be

  5. Active Region Moss: Doppler Shifts from Hinode/EIS Observations

    NASA Technical Reports Server (NTRS)

    Tripathi, Durgesh; Mason, Helen E.; Klimchuk, James A.

    2012-01-01

    Studying the Doppler shifts and the temperature dependence of Doppler shifts in moss regions can help us understand the heating processes in the core of the active regions. In this paper we have used an active region observation recorded by the Extreme-ultraviolet Imaging Spectrometer (EIS) onboard Hinode on 12-Dec- 2007 to measure the Doppler shifts in the moss regions. We have distinguished the moss regions from the rest of the active region by defining a low density cut-off as derived by Tripathi et al. (2010). We have carried out a very careful analysis of the EIS wavelength calibration based on the method described in Young, O Dwyer and Mason (2012). For spectral lines having maximum sensitivity between log T = 5.85 and log T = 6.25 K, we find that the velocity distribution peaks at around 0 km/s with an estimated error of 4 km/s. The width of the distribution decreases with temperature. The mean of the distribution shows a blue shift which increases with increasing temperature and the distribution also shows asymmetries towards blue-shift. Comparing these results with observables predicted from different coronal heating models, we find that these results are consistent with both steady and impulsive heating scenarios. Further observational constraints are needed to distinguish between these two heating scenarios.

  6. Active region moss. Basic physical parameters and their temporal variation

    NASA Astrophysics Data System (ADS)

    Tripathi, D.; Mason, H. E.; Del Zanna, G.; Young, P. R.

    2010-07-01

    Context. Active region moss are transition region phenomena, first noted in the images recorded by the Transition Region and Coronal Explorer (TRACE) in λ171. Moss regions are thought to be the footpoints of hot loops (3-5 MK) seen in the core of active regions. These hot loops appear “fuzzy” (unresolved). Therefore, it is difficult to study the physical plasma parameters in individual hot core loops and hence their heating mechanisms. Moss regions provide an excellent opportunity to study the physics of hot loops. In addition, they allow us to study the transition region dynamics in the footpoint regions. Aims: To derive the physical plasma parameters such as temperature, electron density, and filling factors in moss regions and to study their variation over a short (an hour) and a long time period (5 consecutive days). Methods: Primarily, we have analyzed spectroscopic observations recorded by the Extreme-ultraviolet Imaging Spectrometer (EIS) aboard Hinode. In addition we have used supplementary observations taken from TRACE and the X-Ray Telescope (XRT) aboard Hinode. Results: The moss emission is strongest in the Fe XII and Fe XIII lines. Based on analyses using line ratios and emission measure we found that moss regions have a characteristic temperature of log T[K] = 6.2. The temperature structure in moss region remains almost identical from one region to another and it does not change with time. The electron densities measured at different locations in the moss regions using Fe XII ratios are about 1-3 × 1010 cm-3 and about 2-4 × 109 cm-3 using Fe XIII and Fe XIV. The densities in the moss regions are similar in different places and show very little variation over short and long time scales. The derived electron density substantially increased (by a factor of about 3-4 or even more in some cases) when a background subtraction was performed. The filling factor of the moss plasma can vary between 0.1-1 and the path length along which the emission

  7. Molecular Cloning and Characterization of an Acetylcholinesterase cDNA in the Brown Planthopper, Nilaparvata lugens

    PubMed Central

    Yang, Zhifan; Chen, Jun; Chen, Yongqin; Jiang, Sijing

    2010-01-01

    A full cDNA encoding an acetylcholinesterase (AChE, EC 3.1.1.7) was cloned and characterized from the brown planthopper, Nilaparvata lugens Stål (Hemiptera: Delphacidae). The complete cDNA (2467 bp) contains a 1938-bp open reading frame encoding 646 amino acid residues. The amino acid sequence of the AChE deduced from the cDNA consists of 30 residues for a putative signal peptide and 616 residues for the mature protein with a predicted molecular weight of 69,418. The three residues (Ser242, Glu371, and His485) that putatively form the catalytic triad and the six Cys that form intra-subunit disulfide bonds are completely conserved, and 10 out of the 14 aromatic residues lining the active site gorge of the AChE are also conserved. Northern blot analysis of poly(A)+ RNA showed an approximately 2.6-kb transcript, and Southern blot analysis revealed there likely was just a single copy of this gene in N. lugens. The deduced protein sequence is most similar to AChE of Nephotettix cincticeps with 83% amino acid identity. Phylogenetic analysis constructed with 45 AChEs from 30 species showed that the deduced N. lugens AChE formed a cluster with the other 8 insect AChE2s. Additionally, the hypervariable region and amino acids specific to insect AChE2 also existed in the AChE of N. lugens. The results revealed that the AChE cDNA cloned in this work belongs to insect AChE2 subgroup, which is orthologous to Drosophila AChE. Comparison of the AChEs between the susceptible and resistant strains revealed a point mutation, Gly185Ser, is likely responsible for the insensitivity of the AChE to methamidopho in the resistant strain. PMID:20874389

  8. Molecular, biochemical and histochemical characterization of two acetylcholinesterase cDNAs from the German cockroach Blattella germanica.

    PubMed

    Kim, J I; Jung, C S; Koh, Y H; Lee, S H

    2006-08-01

    Full length cDNAs encoding two acetylcholinesterases (AChEs; Bgace1 and Bgace2) were cloned and characterized from the German cockroach, Blattella germanica. Sequence analyses showed that both genes possess all the typical features of ace, and that Bgace1 is orthologous to the insect ace1 whereas Bgace2 is to the insect ace2. Transcript level of Bgace1 was significantly higher (c. 10 fold) than that of Bgace2 in all 11 tissues examined, suggesting that Bgace1 likely encodes a predominant AChE. Multiple AChE bands were identified by native polyacrylamide gel electrophoresis and isoelectricfocusing from various tissue preparations, among which ganglia produced distinct two major and two minor AChE bands, indicative of the presence of at least two active AChEs. B. germanica AChEs appeared to be mainly localized in the central nervous system as demonstrated by histochemical activity staining, together with quantitative analysis of Bgace transcripts. Fluorescence in situ hybridization of the 1st thoracic ganglion confirmed that Bgace1 is predominantly transcribed and further showed that its transcript is found in almost entire region of inter or motor neurones including the cell bodies and axonal/dendritic branches. Bgace2 transcript is found only in the subset of neurones, particularly in the cell body. In addition, certain neurones were observed to express Bgace1 only.

  9. Thermal denaturation of Bungarus fasciatus acetylcholinesterase: Is aggregation a driving force in protein unfolding?

    PubMed Central

    Shin, I.; Wachtel, E.; Roth, E.; Bon, C.; Silman, I.; Weiner, L.

    2002-01-01

    A monomeric form of acetylcholinesterase from the venom of Bungarus fasciatus is converted to a partially unfolded molten globule species by thermal inactivation, and subsequently aggregates rapidly. To separate the kinetics of unfolding from those of aggregation, single molecules of the monomeric enzyme were encapsulated in reverse micelles of Brij 30 in 2,2,4-trimethylpentane, or in large unilamellar vesicles of egg lecithin/cholesterol at various protein/micelle (vesicle) ratios. The first-order rate constant for thermal inactivation at 45°C, of single molecules entrapped within the reverse micelles (0.031 min−1), was higher than in aqueous solution (0.007 min−1) or in the presence of normal micelles (0.020 min−1). This clearly shows that aggregation does not provide the driving force for thermal inactivation of BfAChE. Within the large unilamellar vesicles, at average protein/vesicle ratios of 1:1 and 10:1, the first-order rate constants for thermal inactivation of the encapsulated monomeric acetylcholinesterase, at 53°C, were 0.317 and 0.342 min−1, respectively. A crosslinking technique, utilizing the photosensitive probe, hypericin, showed that thermal denaturation produces a distribution of species ranging from dimers through to large aggregates. Consequently, at a protein/vesicle ratio of 10:1, aggregation can occur upon thermal denaturation. Thus, these experiments also demonstrate that aggregation does not drive the thermal unfolding of Bungarus fasciatus acetylcholinesterase. Our experimental approach also permitted monitoring of recovery of enzymic activity after thermal denaturation in the absence of a competing aggregation process. Whereas no detectable recovery of enzymic activity could be observed in aqueous solution, up to 23% activity could be obtained for enzyme sequestered in the reverse micelles. PMID:12142456

  10. On the Active Region Bright Grains Observed in the Transition Region Imaging Channels of IRIS

    NASA Astrophysics Data System (ADS)

    Skogsrud, H.; Rouppe van der Voort, L.; De Pontieu, B.

    2016-02-01

    The Interface Region Imaging Spectrograph (IRIS) provides spectroscopy and narrow band slit-jaw (SJI) imaging of the solar chromosphere and transition region at unprecedented spatial and temporal resolutions. Combined with high-resolution context spectral imaging of the photosphere and chromosphere as provided by the Swedish 1 m Solar Telescope (SST), we can now effectively trace dynamic phenomena through large parts of the solar atmosphere in both space and time. IRIS SJI 1400 images from active regions, which primarily sample the transition region with the Si iv 1394 and 1403 Å lines, reveal ubiquitous bright “grains” which are short-lived (two to five minute) bright roundish small patches of sizes 0.″5-1.″7 that generally move limbward with velocities up to about 30 km s-1. In this paper, we show that many bright grains are the result of chromospheric shocks impacting the transition region. These shocks are associated with dynamic fibrils (DFs), most commonly observed in Hα. We find that the grains show the strongest emission in the ascending phase of the DF, that the emission is strongest toward the top of the DF, and that the grains correspond to a blueshift and broadening of the Si iv lines. We note that the SJI 1400 grains can also be observed in the SJI 1330 channel which is dominated by C ii lines. Our observations show that a significant part of the active region transition region dynamics is driven from the chromosphere below rather than from coronal activity above. We conclude that the shocks that drive DFs also play an important role in the heating of the upper chromosphere and lower transition region.

  11. ON THE ACTIVE REGION BRIGHT GRAINS OBSERVED IN THE TRANSITION REGION IMAGING CHANNELS OF IRIS

    SciTech Connect

    Skogsrud, H.; Voort, L. Rouppe van der; Pontieu, B. De

    2016-02-01

    The Interface Region Imaging Spectrograph (IRIS) provides spectroscopy and narrow band slit-jaw (SJI) imaging of the solar chromosphere and transition region at unprecedented spatial and temporal resolutions. Combined with high-resolution context spectral imaging of the photosphere and chromosphere as provided by the Swedish 1 m Solar Telescope (SST), we can now effectively trace dynamic phenomena through large parts of the solar atmosphere in both space and time. IRIS SJI 1400 images from active regions, which primarily sample the transition region with the Si iv 1394 and 1403 Å lines, reveal ubiquitous bright “grains” which are short-lived (two to five minute) bright roundish small patches of sizes 0.″5–1.″7 that generally move limbward with velocities up to about 30 km s{sup −1}. In this paper, we show that many bright grains are the result of chromospheric shocks impacting the transition region. These shocks are associated with dynamic fibrils (DFs), most commonly observed in Hα. We find that the grains show the strongest emission in the ascending phase of the DF, that the emission is strongest toward the top of the DF, and that the grains correspond to a blueshift and broadening of the Si iv lines. We note that the SJI 1400 grains can also be observed in the SJI 1330 channel which is dominated by C ii lines. Our observations show that a significant part of the active region transition region dynamics is driven from the chromosphere below rather than from coronal activity above. We conclude that the shocks that drive DFs also play an important role in the heating of the upper chromosphere and lower transition region.

  12. Design, synthesis, and characterization of novel, nonquaternary reactivators of GF-inhibited human acetylcholinesterase.

    PubMed

    McHardy, Stanton F; Bohmann, Jonathan A; Corbett, Michael R; Campos, Bismarck; Tidwell, Michael W; Thompson, Paul Marty; Bemben, Chris J; Menchaca, Tony A; Reeves, Tony E; Cantrell, William R; Bauta, William E; Lopez, Ambrosio; Maxwell, Donald M; Brecht, Karen M; Sweeney, Richard E; McDonough, John

    2014-04-01

    The goal of this research was to identify structurally novel, non-quaternarypyridinium reactivators of GF (cyclosarin)-inhibited hAChE that possess the capacity to mediate in vitro reactivation of GF-inhibited human acetylcholinesterase (hAChE). New compounds were designed, synthesized and assessed in GF-inhibited hAChE assays. Structure activity relationships for AChE binding and reactivation of GF-inhibited hAChE were developed. Lead compounds from two different chemical series, represented by compounds 17 and 38, displayed proficient in vitro reactivation of GF-inhibited hAChE, while also possessing low inhibition of native enzyme.

  13. Design, synthesis, and evaluation of benzophenone derivatives as novel acetylcholinesterase inhibitors.

    PubMed

    Belluti, Federica; Piazzi, Lorna; Bisi, Alessandra; Gobbi, Silvia; Bartolini, Manuela; Cavalli, Andrea; Valenti, Piero; Rampa, Angela

    2009-03-01

    Starting from a structure-based drug design, new acetylcholinesterase inhibitors were designed and synthesized as analogues of donepezil. The compounds were composed by an aromatic function and a tertiary amino moiety connected by a suitable spacer. In particular, the benzophenone nucleus and the N,N-benzylmethylamine function were selected. The easily accessible three-step synthesis of these compounds resulted to be significantly less difficult and expensive than that of donepezil. Several compounds possess anti-cholinesterase activity in the order of micro and sub-micromolar. Particularly, compounds 1 and 10 were the most potent inhibitors of the series.

  14. Socioeconomic and regional differences in active transportation in Brazil

    PubMed Central

    de Sá, Thiago Hérick; Pereira, Rafael Henrique Moraes; Duran, Ana Clara; Monteiro, Carlos Augusto

    2016-01-01

    ABSTRACT OBJECTIVE To present national estimates regarding walking or cycling for commuting in Brazil and in 10 metropolitan regions. METHODS By using data from the Health section of 2008’s Pesquisa Nacional por Amostra de Domicílio (Brazil’s National Household Sample Survey), we estimated how often employed people walk or cycle to work, disaggregating our results by sex, age range, education level, household monthly income per capita, urban or rural address, metropolitan regions, and macro-regions in Brazil. Furthermore, we estimated the distribution of this same frequency according to quintiles of household monthly income per capita in each metropolitan region of the country. RESULTS A third of the employed men and women walk or cycle from home to work in Brazil. For both sexes, this share decreases as income and education levels rise, and it is higher among younger individuals, especially among those living in rural areas and in the Northeast region of the country. Depending on the metropolitan region, the practice of active transportation is two to five times more frequent among low-income individuals than among high-income individuals. CONCLUSIONS Walking or cycling to work in Brazil is most frequent among low-income individuals and the ones living in less economically developed areas. Active transportation evaluation in Brazil provides important information for public health and urban mobility policy-making PMID:27355465

  15. Novel acetylcholinesterase target site for malaria mosquito control.

    PubMed

    Pang, Yuan-Ping

    2006-12-20

    Current anticholinesterase pesticides were developed during World War II and are toxic to mammals because they target a catalytic serine residue of acetylcholinesterases (AChEs) in insects and in mammals. A sequence analysis of AChEs from 73 species and a three-dimensional model of a malaria-carrying mosquito (Anopheles gambiae) AChE (AgAChE) reported here show that C286 and R339 of AgAChE are conserved at the opening of the active site of AChEs in 17 invertebrate and four insect species, respectively. Both residues are absent in the active site of AChEs of human, monkey, dog, cat, cattle, rabbit, rat, and mouse. The 17 invertebrates include house mosquito, Japanese encephalitis mosquito, African malaria mosquito, German cockroach, Florida lancelet, rice leaf beetle, African bollworm, beet armyworm, codling moth, diamondback moth, domestic silkworm, honey bee, oat or wheat aphid, the greenbug, melon or cotton aphid, green peach aphid, and English grain aphid. The four insects are house mosquito, Japanese encephalitis mosquito, African malaria mosquito, and German cockroach. The discovery of the two invertebrate-specific residues enables the development of effective and safer pesticides that target the residues present only in mosquito AChEs rather than the ubiquitous serine residue, thus potentially offering an effective control of mosquito-borne malaria. Anti-AgAChE pesticides can be designed to interact with R339 and subsequently covalently bond to C286. Such pesticides would be toxic to mosquitoes but not to mammals.

  16. Freeze-frame inhibitor captures acetylcholinesterase in a unique conformation

    PubMed Central

    Bourne, Yves; Kolb, Hartmuth C.; Radić, Zoran; Sharpless, K. Barry; Taylor, Palmer; Marchot, Pascale

    2004-01-01

    The 1,3-dipolar cycloaddition reaction between unactivated azides and acetylenes proceeds exceedingly slowly at room temperature. However, considerable rate acceleration is observed when this reaction occurs inside the active center gorge of acetylcholinesterase (AChE) between certain azide and acetylene reactants, attached via methylene chains to specific inhibitor moieties selective for the active center and peripheral site of the enzyme. AChE catalyzes the formation of its own inhibitor in a highly selective fashion: only a single syn1-triazole regioisomer with defined substitution positions and linker distances is generated from a series of reagent combinations. Inhibition measurements revealed this syn1-triazole isomer to be the highest affinity reversible organic inhibitor of AChE with association rate constants near the diffusion limit. The corresponding anti1 isomer, not formed by the enzyme, proved to be a respectable but weaker inhibitor. The crystal structures of the syn1- and anti1-mouse AChE complexes at 2.45- to 2.65-Å resolution reveal not only substantial binding contributions from the triazole moieties, but also that binding of the syn1 isomer induces large and unprecedented enzyme conformational changes not observed in the anti1 complex nor predicted from structures of the apoenzyme and complexes with the precursor reactants. Hence, the freeze-frame reaction offers both a strategically original approach for drug discovery and a means for kinetically controlled capture, as a high-affinity complex between the enzyme and its self-created inhibitor, of a highly reactive minor abundance conformer of a fluctuating protein template. PMID:14757816

  17. Freeze-frame inhibitor captures acetylcholinesterase in a unique conformation.

    PubMed

    Bourne, Yves; Kolb, Hartmuth C; Radić, Zoran; Sharpless, K Barry; Taylor, Palmer; Marchot, Pascale

    2004-02-10

    The 1,3-dipolar cycloaddition reaction between unactivated azides and acetylenes proceeds exceedingly slowly at room temperature. However, considerable rate acceleration is observed when this reaction occurs inside the active center gorge of acetylcholinesterase (AChE) between certain azide and acetylene reactants, attached via methylene chains to specific inhibitor moieties selective for the active center and peripheral site of the enzyme. AChE catalyzes the formation of its own inhibitor in a highly selective fashion: only a single syn1-triazole regioisomer with defined substitution positions and linker distances is generated from a series of reagent combinations. Inhibition measurements revealed this syn1-triazole isomer to be the highest affinity reversible organic inhibitor of AChE with association rate constants near the diffusion limit. The corresponding anti1 isomer, not formed by the enzyme, proved to be a respectable but weaker inhibitor. The crystal structures of the syn1- and anti1-mouse AChE complexes at 2.45- to 2.65-A resolution reveal not only substantial binding contributions from the triazole moieties, but also that binding of the syn1 isomer induces large and unprecedented enzyme conformational changes not observed in the anti1 complex nor predicted from structures of the apoenzyme and complexes with the precursor reactants. Hence, the freeze-frame reaction offers both a strategically original approach for drug discovery and a means for kinetically controlled capture, as a high-affinity complex between the enzyme and its self-created inhibitor, of a highly reactive minor abundance conformer of a fluctuating protein template.

  18. Urban, Rural, and Regional Variations in Physical Activity

    ERIC Educational Resources Information Center

    Martin, Sarah Levin; Kirkner, Gregory J.; Mayo, Kelly; Matthews, Charles E.; Durstine, Larry; Hebert, James R.

    2005-01-01

    Purpose: There is some speculation about geographic differences in physical activity (PA) levels. We examined the prevalence of physical inactivity (PIA) and whether US citizens met the recommended levels of PA across the United States. In addition, the association between PIA/PA and degree of urbanization in the 4 main US regions (Northeast,…

  19. Inferred flows of electric currents in solar active regions

    NASA Technical Reports Server (NTRS)

    Ding, Y. J.; Hong, Q. F.; Hagyard, M. J.; Deloach, A. C.

    1985-01-01

    Techniques to identify sources of major current systems in active regions and their channels of flow are explored. Measured photospheric vector magnetic fields together with high resolution white light and H-alpha photographs provide the data base to derive the current systems in the photosphere and chromosphere of a solar active region. Simple mathematical constructions of active region fields and currents are used to interpret these data under the assumptions that the fields in the lower atmosphere (below 200 km) may not be force free but those in the chromosphere and higher are. The results obtained for the complex active region AR 2372 are: (1) Spots exhibiting significant spiral structure in the penumbral filaments were the source of vertical currents at the photospheric surface; (2) Magnetic neutral lines where the transverse magnetic field was strongly sheared were channels along which a strong current system flowed; (3) The inferred current systems produced a neutral sheet and oppositely-flowing currents in the area of the magnetic delta configuration that was the site of flaring.

  20. IFLA General Conference, 1987. Division of Regional Activities. Papers.

    ERIC Educational Resources Information Center

    International Federation of Library Associations, The Hague (Netherlands).

    Six of the seven papers in this collection focus on regional library activities in Africa, Asia and Oceania, and Latin America and the Caribbean: (1) "Libraries and Information Services in a Changing World: The Challenges African Information Services Face at the End of the 1980s" (Dejen Abate, Ethiopia); (2) "The Computer and…

  1. Early life stress affects limited regional brain activity in depression.

    PubMed

    Du, Lian; Wang, Jingjie; Meng, Ben; Yong, Na; Yang, Xiangying; Huang, Qingling; Zhang, Yan; Yang, Lingling; Qu, Yuan; Chen, Zhu; Li, Yongmei; Lv, Fajin; Hu, Hua

    2016-05-03

    Early life stress (ELS) can alter brain function and increases the risk of major depressive disorder (MDD) in later life. This study investigated whether ELS contributes to differences in regional brain activity between MDD patients and healthy controls (HC), as measured by amplitude of low-frequency fluctuation (ALFF)/fractional (f)ALFF. Eighteen first-episode, treatment-naïve MDD patients and HC were assessed with the Childhood Trauma Questionnaire and resting-state functional magnetic resonance imaging. We compared ALFF/fALFF between MDD patients and HC, with or without controlling for ELS, and determined whether ELS level was correlated with regional brain activity in each group. After regressing out ELS, we found that ALFF increased in bilateral amygdala and left orbital/cerebellum, while fALFF decreased in left inferior temporal and right middle frontal gyri in MDD patients relative to controls. ELS positively correlated with regional activity in the left cerebellum in MDD and in the right post-central/inferior temporal/superior frontal cingulate, inferior frontal gyrus and bilateral cerebellum in HC. Our findings indicate that there is only very limited region showing correlation between ELS and brain activity in MDD, while diverse areas in HC, suggesting ELS has few impacts on MDD patients.

  2. A solar cycle timing predictor - The latitude of active regions

    NASA Technical Reports Server (NTRS)

    Schatten, Kenneth H.

    1990-01-01

    A 'Spoerer butterfly' method is used to examine solar cycle 22. It is shown from the latitude of active regions that the cycle can now be expected to peak near November 1989 + or - 8 months, basically near the latter half of 1989.

  3. Unwinding motion of a twisted active region filament

    SciTech Connect

    Yan, X. L.; Xue, Z. K.; Kong, D. F.; Liu, J. H.; Xu, C. L.

    2014-12-10

    To better understand the structures of active region filaments and the eruption process, we study an active region filament eruption in active region NOAA 11082 in detail on 2010 June 22. Before the filament eruption, the opposite unidirectional material flows appeared in succession along the spine of the filament. The rising of the filament triggered two B-class flares at the upper part of the filament. As the bright material was injected into the filament from the sites of the flares, the filament exhibited a rapid uplift accompanying the counterclockwise rotation of the filament body. From the expansion of the filament, we can see that the filament consisted of twisted magnetic field lines. The total twist of the filament is at least 5π obtained by using a time slice method. According to the morphology change during the filament eruption, it is found that the active region filament was a twisted flux rope and its unwinding motion was like a solar tornado. We also find that there was a continuous magnetic helicity injection before and during the filament eruption. It is confirmed that magnetic helicity can be transferred from the photosphere to the filament. Using the extrapolated potential fields, the average decay index of the background magnetic fields over the filament is 0.91. Consequently, these findings imply that the mechanism of solar filament eruption could be due to the kink instability and magnetic helicity accumulation.

  4. Early life stress affects limited regional brain activity in depression

    PubMed Central

    Du, Lian; Wang, Jingjie; Meng, Ben; Yong, Na; Yang, Xiangying; Huang, Qingling; Zhang, Yan; Yang, Lingling; Qu, Yuan; Chen, Zhu; Li, Yongmei; Lv, Fajin; Hu, Hua

    2016-01-01

    Early life stress (ELS) can alter brain function and increases the risk of major depressive disorder (MDD) in later life. This study investigated whether ELS contributes to differences in regional brain activity between MDD patients and healthy controls (HC), as measured by amplitude of low-frequency fluctuation (ALFF)/fractional (f)ALFF. Eighteen first-episode, treatment-naïve MDD patients and HC were assessed with the Childhood Trauma Questionnaire and resting-state functional magnetic resonance imaging. We compared ALFF/fALFF between MDD patients and HC, with or without controlling for ELS, and determined whether ELS level was correlated with regional brain activity in each group. After regressing out ELS, we found that ALFF increased in bilateral amygdala and left orbital/cerebellum, while fALFF decreased in left inferior temporal and right middle frontal gyri in MDD patients relative to controls. ELS positively correlated with regional activity in the left cerebellum in MDD and in the right post-central/inferior temporal/superior frontal cingulate, inferior frontal gyrus and bilateral cerebellum in HC. Our findings indicate that there is only very limited region showing correlation between ELS and brain activity in MDD, while diverse areas in HC, suggesting ELS has few impacts on MDD patients. PMID:27138376

  5. β-amyloid decreases detectable endothelial nitric oxide synthase in human erythrocytes: a role for membrane acetylcholinesterase.

    PubMed

    Misiti, Francesco; Carelli-Alinovi, Cristiana; Sampaolese, Beatrice; Giardina, Bruno

    2012-08-01

    Until few years ago, many studies of Alzheimer's disease investigated the effects of this syndrome in the central nervous system. Only recently, the detection of amyloid beta peptide (Aβ) in the blood has evidenced the necessity to extend studies on extraneuronal cells, particularly on erythrocytes. Aβ is also present in brain capillaries, where it interacts with the erythrocytes, inducing several metabolic and functional alterations. Recently, functionally active endothelial type nitric oxide synthase (eNOS) was discovered in human erythrocytes. The goal of the present study was to evidence the effect of Aβ on erythrocyte eNOS. We found that Aβ following to 24-h exposure causes a decrease in the immune staining of erythrocyte eNOS. Concurrently, Aβ alters erythrocyte cell morphology, decreases nitrites and nitrates levels, and affects membrane acetylcholinesterase activity. Propidium, an acetylcholinesterase inhibitor, was able to reverse the effects elicited by Aβ. These events could contribute to the vascular alterations associated with Alzheimer's disease disease.

  6. Doppler Shifts in Active Region Moss Using SOHO/SUMER

    NASA Astrophysics Data System (ADS)

    Winebarger, Amy; Tripathi, Durgesh; Mason, Helen E.; Del Zanna, Giulio

    2013-04-01

    The velocity of the plasma at the footpoint of hot loops in active region cores can be used to discriminate between different heating frequencies. Velocities on the order of a few kilometers per second would indicate low-frequency heating on sub-resolution strands, while velocities close to zero would indicate high-frequency (steady) heating. To discriminate between these two values requires accurate velocity measurements; previous velocity measurements suffer from large uncertainties, mainly due to the lack of an absolute wavelength reference scale. In this paper, we determine the velocity in the loop footpoints using observations from Solar Ultraviolet Measurements of Emitted Radiation (SUMER) on Solar and Heliospheric Observatory. We use neutral spectral lines to determine the wavelength scale of the observations with an uncertainty in the absolute velocity of <3.5 km s-1 and co-aligned Transition Region and Coronal Explorer (TRACE) images to identify footpoint regions. We studied three different active regions and found average redshifts in the Ne VIII 770 Å emission line (formed at 6 × 105 K) of 5.17 ± 5.37 km s-1 and average redshifts in the C IV 1548 and 1550 Å emission lines (formed at 1 × 105 K) of 13.94 ± 4.93 km s-1 and 14.91 ± 6.09 km s-1, respectively. We find no correlation between the brightness in the spectral line and the measured velocity, nor do we find correlation between the Ne VIII and C IV velocities measured co-spatially and co-temporally. SUMER scanned two of the active regions twice; in those active regions we find positive correlation between the co-spatial velocities measured during the first and second scans. These results provide definitive and quantitative measurements for comparisons with simulations of different coronal heating mechanisms.

  7. Regional differences in rat conjunctival ion transport activities.

    PubMed

    Yu, Dongfang; Thelin, William R; Rogers, Troy D; Stutts, M Jackson; Randell, Scott H; Grubb, Barbara R; Boucher, Richard C

    2012-10-01

    Active ion transport and coupled osmotic water flow are essential to maintain ocular surface health. We investigated regional differences in the ion transport activities of the rat conjunctivas and compared these activities with those of cornea and lacrimal gland. The epithelial sodium channel (ENaC), sodium/glucose cotransporter 1 (Slc5a1), transmembrane protein 16 (Tmem16a, b, f, and g), cystic fibrosis transmembrane conductance regulator (Cftr), and mucin (Muc4, 5ac, and 5b) mRNA expression was characterized by RT-PCR. ENaC proteins were measured by Western blot. Prespecified regions (palpebral, fornical, and bulbar) of freshly isolated conjunctival tissues and cell cultures were studied electrophysiologically with Ussing chambers. The transepithelial electrical potential difference (PD) of the ocular surface was also measured in vivo. The effect of amiloride and UTP on the tear volume was evaluated in lacrimal gland excised rats. All selected genes were detected but with different expression patterns. We detected αENaC protein in all tissues, βENaC in palpebral and fornical conjunctiva, and γENaC in all tissues except lacrimal glands. Electrophysiological studies of conjunctival tissues and cell cultures identified functional ENaC, SLC5A1, CFTR, and TMEM16. Fornical conjunctiva exhibited the most active ion transport under basal conditions amongst conjunctival regions. PD measurements confirmed functional ENaC-mediated Na(+) transport on the ocular surface. Amiloride and UTP increased tear volume in lacrimal gland excised rats. This study demonstrated that the different regions of the conjunctiva exhibited a spectrum of ion transport activities. Understanding the specific functions of distinct regions of the conjunctiva may foster a better understanding of the physiology maintaining hydration of the ocular surface.

  8. Regional differences in rat conjunctival ion transport activities

    PubMed Central

    Yu, Dongfang; Thelin, William R.; Rogers, Troy D.; Stutts, M. Jackson; Randell, Scott H.; Grubb, Barbara R.

    2012-01-01

    Active ion transport and coupled osmotic water flow are essential to maintain ocular surface health. We investigated regional differences in the ion transport activities of the rat conjunctivas and compared these activities with those of cornea and lacrimal gland. The epithelial sodium channel (ENaC), sodium/glucose cotransporter 1 (Slc5a1), transmembrane protein 16 (Tmem16a, b, f, and g), cystic fibrosis transmembrane conductance regulator (Cftr), and mucin (Muc4, 5ac, and 5b) mRNA expression was characterized by RT-PCR. ENaC proteins were measured by Western blot. Prespecified regions (palpebral, fornical, and bulbar) of freshly isolated conjunctival tissues and cell cultures were studied electrophysiologically with Ussing chambers. The transepithelial electrical potential difference (PD) of the ocular surface was also measured in vivo. The effect of amiloride and UTP on the tear volume was evaluated in lacrimal gland excised rats. All selected genes were detected but with different expression patterns. We detected αENaC protein in all tissues, βENaC in palpebral and fornical conjunctiva, and γENaC in all tissues except lacrimal glands. Electrophysiological studies of conjunctival tissues and cell cultures identified functional ENaC, SLC5A1, CFTR, and TMEM16. Fornical conjunctiva exhibited the most active ion transport under basal conditions amongst conjunctival regions. PD measurements confirmed functional ENaC-mediated Na+ transport on the ocular surface. Amiloride and UTP increased tear volume in lacrimal gland excised rats. This study demonstrated that the different regions of the conjunctiva exhibited a spectrum of ion transport activities. Understanding the specific functions of distinct regions of the conjunctiva may foster a better understanding of the physiology maintaining hydration of the ocular surface. PMID:22814399

  9. Active sonar, beaked whales and European regional policy.

    PubMed

    Dolman, Sarah J; Evans, Peter G H; Notarbartolo-di-Sciara, Giuseppe; Frisch, Heidrun

    2011-01-01

    Various reviews, resolutions and guidance from international and regional fora have been produced in recent years that acknowledge the significance of marine noise and its potential impacts on cetaceans. Within Europe, ACCOBAMS and ASCOBANS have shown increasing attention to the issue. The literature highlights concerns surrounding the negative impacts of active sonar on beaked whales in particular, where concerns primarily relate to the use of mid-frequency active sonar (1-10kHz), as used particularly in military exercises. The authors review the efforts that European regional policies have undertaken to acknowledge and manage possible negative impacts of active sonar and how these might assist the transition from scientific research to policy implementation, including effective management and mitigation measures at a national level.

  10. Transcriptionally active genome regions are preferred targets for retrovirus integration.

    PubMed Central

    Scherdin, U; Rhodes, K; Breindl, M

    1990-01-01

    We have analyzed the transcriptional activity of cellular target sequences for Moloney murine leukemia virus integration in mouse fibroblasts. At least five of the nine random, unselected integration target sequences studied showed direct evidence for transcriptional activity by hybridization to nuclear run-on transcripts prepared from uninfected cells. At least four of the sequences contained multiple recognition sites for several restriction enzymes that cut preferentially in CpG-rich islands, indicating integration into 5' or 3' ends or flanking regions of genes. Assuming that only a minor fraction (less than 20%) of the genome is transcribed in mammalian cells, we calculated the probability that this association of retroviral integration sites with transcribed sequences is due to chance to be very low (1.6 x 10(-2]. Thus, our results strongly suggest that transcriptionally active genome regions are preferred targets for retrovirus integration. Images PMID:2296087

  11. An optimized extraction technique for acetylcholinesterase inhibitors from the Camellia japonica seed cake by using response surface methodology.

    PubMed

    Kim, Jae Kyeom; Kim, Cho Rong; Lim, Ho-Jeong; Nam, Sang Hae; Joo, Ok Soo; Shin, Dong-Hoon; Shin, Eui-Cheol

    2014-01-01

    The response surface methodology (RSM) was used to optimize the extraction conditions for the acetylcholinesterase (AchE) inhibitory activity and extraction yield from Camellia japonica seed cake. Predicted values for AchE inhibition and extraction yield were 19.41 and 13.35%, respectively, which are in good agreement with the experimental values from validation, suggesting that RSM may provide a useful tool to optimization processes.

  12. Introducing Dynamic Combinatorial Chemistry: Probing the Substrate Selectivity of Acetylcholinesterase

    ERIC Educational Resources Information Center

    Angelin, Marcus; Larsson, Rikard; Vongvilai, Pornrapee; Ramstrom, Olof

    2010-01-01

    In this laboratory experiment, college students are introduced to dynamic combinatorial chemistry (DCC) and apply it to determine the substrate selectivity of acetylcholinesterase (AChE). Initially, the students construct a chemical library of dynamically interchanging thioesters and thiols. Then, AChE is added and allowed to select and hydrolyze…

  13. Acetylcholinesterases of Blood-feeding Flies and Ticks

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Acetylcholinesterase (AChE) is the biochemical target of organophosphate (OP) and carbamate pesticides for invertebrates, vertebrate nerve agents, and AChE inhibitors used to reduce effects of Alzheimer’s disease. Organophosphate pesticides (OPs) are widely used to control blood-feeding arthropods, ...

  14. Complexity of acetylcholinesterases in biting flies and ticks

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Acetylcholinesterase (AChE) inhibitors function as pesticides for invertebrates, vertebrate nerve agents, and medicine to reduce cognitive effects of Alzheimer’s disease. Organophosphate (OP) pesticides have been widely used to control biting flies and ticks, however, OP-resistance has compromised c...

  15. Static and Dynamic Modeling of a Solar Active Region

    NASA Astrophysics Data System (ADS)

    Warren, Harry P.; Winebarger, Amy R.

    2007-09-01

    Recent hydrostatic simulations of solar active regions have shown that it is possible to reproduce both the total intensity and the general morphology of the high-temperature emission observed at soft X-ray wavelengths using static heating models. These static models, however, cannot account for the lower temperature emission. In addition, there is ample observational evidence that the solar corona is highly variable, indicating a significant role for dynamical processes in coronal heating. Because they are computationally demanding, full hydrodynamic simulations of solar active regions have not been considered previously. In this paper we make first application of an impulsive heating model to the simulation of an entire active region, AR 8156 observed on 1998 February 16. We model this region by coupling potential field extrapolations to full solutions of the time-dependent hydrodynamic loop equations. To make the problem more tractable we begin with a static heating model that reproduces the emission observed in four different Yohkoh Soft X-Ray Telescope (SXT) filters and consider impulsive heating scenarios that yield time-averaged SXT intensities that are consistent with the static case. We find that it is possible to reproduce the total observed soft X-ray emission in all of the SXT filters with a dynamical heating model, indicating that nanoflare heating is consistent with the observational properties of the high-temperature solar corona. At EUV wavelengths the simulated emission shows more coronal loops, but the agreement between the simulation and the observation is still not acceptable.

  16. THE EVOLUTION OF DARK CANOPIES AROUND ACTIVE REGIONS

    SciTech Connect

    Wang, Y.-M.; Robbrecht, E.; Muglach, K. E-mail: eva.robbrecht@oma.be

    2011-05-20

    As observed in spectral lines originating from the chromosphere, transition region, and low corona, active regions are surrounded by an extensive 'circumfacular' area which is darker than the quiet Sun. We examine the properties of these dark moat- or canopy-like areas using Fe IX 17.1 nm images and line-of-sight magnetograms from the Solar Dynamics Observatory. The 17.1 nm canopies consist of fibrils (horizontal fields containing extreme-ultraviolet-absorbing chromospheric material) clumped into featherlike structures. The dark fibrils initially form a quasiradial or vortical pattern as the low-lying field lines fanning out from the emerging active region connect to surrounding network and intranetwork elements of opposite polarity. The area occupied by the 17.1 nm fibrils expands as supergranular convection causes the active-region flux to spread into the background medium; the outer boundary of the dark canopy stabilizes where the diffusing flux encounters a unipolar region of opposite sign. The dark fibrils tend to accumulate in regions of weak longitudinal field and to become rooted in mixed-polarity flux. To explain the latter observation, we note that the low-lying fibrils are more likely to interact with small loops associated with weak, opposite-polarity flux elements in close proximity, than with high loops anchored inside strong unipolar network flux. As a result, the 17.1 nm fibrils gradually become concentrated around the large-scale polarity inversion lines (PILs), where most of the mixed-polarity flux is located. Systematic flux cancellation, assisted by rotational shearing, removes the field component transverse to the PIL and causes the fibrils to coalesce into long PIL-aligned filaments.

  17. DIVERGENT HORIZONTAL SUB-SURFACE FLOWS WITHIN ACTIVE REGION 11158

    SciTech Connect

    Jain, Kiran; Tripathy, S. C.; Hill, F. E-mail: stripathy@nso.edu

    2015-07-20

    We measure the horizontal subsurface flow in a fast emerging active region (AR; NOAA 11158) using the ring-diagram technique and the Helioseismic and Magnetic Imager high spatial resolution Dopplergrams. This AR had a complex magnetic structure and displayed significant changes in morphology during its disk passage. Over a period of six days from 2011 February 11 to 16, the temporal variation in the magnitude of the total velocity is found to follow the trend of magnetic field strength. We further analyze regions of individual magnetic polarity within AR 11158 and find that the horizontal velocity components in these sub-regions have significant variation with time and depth. The leading and trailing polarity regions move faster than the mixed-polarity region. Furthermore, both zonal and meridional components have opposite signs for trailing and leading polarity regions at all depths showing divergent flows within the AR. We also find a sharp decrease in the magnitude of total horizontal velocity in deeper layers around major flares. It is suggested that the re-organization of magnetic fields during flares, combined with the sunspot rotation, decreases the magnitude of horizontal flows or that the flow kinetic energy has been converted into the energy released by flares. After the decline in flare activity and sunspot rotation, the flows tend to follow the pattern of magnetic activity. We also observe less variation in the velocity components near the surface but these tend to increase with depth, further demonstrating that the deeper layers are more affected by the topology of ARs.

  18. EUV analysis of an active region. [of solar corona in limb region

    NASA Technical Reports Server (NTRS)

    Raghavan, N.; Withbroe, G. L.

    1975-01-01

    A sequence of extreme-ultraviolet (EUV) spectroheliograms of McMath region No. 10283 were obtained by OSO-6. The lines O VI (1032 A) Mg X (625 A), Si XII (499 A), and Fe XVI (335 A) were used to determine coronal temperatures and densities above the active region. A comparison of theoretical and observed line ratios yielded coronal temperatures of 2.2 to 2.3 million K above the active region and 2.0 to 2.1 million K in the surrounding area. The temperatures derived from ratios involving the O VI intensities are systematically higher than the others. This is attributed to an error in the theoretical O VI intensities. The intensities observed above the limb are compared with intensities predicted by a simple model based on cylindrical geometry. The overall agreement shows that the assumption of an isothermal corona in hydrostatic equilibrium above the active region is a resonable working hypothesis and that the adopted geometrical model for the electron density distribution is adequate.

  19. The evolution and orientation of early cycle 22 active regions

    NASA Technical Reports Server (NTRS)

    Cannon, Anne T.; Marquette, William H.

    1991-01-01

    The evolution of six major active regions which appeared during the first phase of the present solar cycle (cycle 22) has been studied. It was found that the northern hemisphere regions exhibited a broad range of evolutionary behavior in which the commonly accepted 'normal pattern' (whereby the follower flux moves preferentially polewards ahead of the leader flux) is represented at one end of the range. At the other end of the range, the leader flux is displaced polewards of the follower flux. In the latter cases equatorward extensions of the polar coronal hole are noted.

  20. A 45-kDa acetylcholinesterase protoxin of Aeromonas hydrophila: purification and immunogenicity in fish.

    PubMed

    Pérez, M J; Rodríguez, L A; Fernández-Briera, A; Nieto, T P

    2002-05-21

    A rabbit antiserum to the 15-kDa acetylcholinesterase toxin neutralised the lethal effect of the 15-kDa toxin of Aeromonas hydrophila when injected into trout. However, immunisation of fish with the 15-kDa toxoid failed to induce an antibody response, and a higher molecular mass form of this toxin was purified from the extracellular products with the aim of inducing an immune response in fish. The optimal conditions for production of extracellular products by A. hydrophila strain B32 were studied to increase the concentration of this protoxin. The extracellular products were fractionated by molecular exclusion chromatography to yield a purified protoxin with an estimated molecular mass of 45 kDa by SDS-PAGE and which gave a positive reaction in Western blotting with the rabbit anti-15-kDa toxin serum. Since the 45-kDa protoxin showed lower specific acetylcholinesterase activity than the active 15-kDa toxin, the behaviour of the active site was studied using specific inhibitors. This 45-kDa protoxin was 13.3-fold less toxic than the 15-kDa toxin and induced antibody production in fish.

  1. Is acetylcholinesterase a biomarker of susceptibility in Daphnia magna (Crustacea, Cladocera) after deltamethrin exposure?

    PubMed

    Toumi, Héla; Boumaiza, Moncef; Millet, Maurice; Radetski, Claudemir Marcos; Felten, Vincent; Férard, Jean François

    2015-02-01

    In the present study, we explored the possibility of using the acetylcholinesterase (AChE) as a biomarker after deltamethrin (pyrethroid insecticide) exposure with three strains of the cladoceran Daphnia magna. Four calculated time-weighted deltamethrin concentrations (20.1, 40.3, 80.6 and 161.3 ng L(-1)) were compared against control acetylcholinesterase activity. Our results showed that after 48 h of deltamethrin exposure, all treatments induced a significant decrease of AChE activities whatever the three considered strains. However, diverse responses were registered in terms of lowest observed effect concentrations (LOEC: 80.6 ng L(-1) for strain 1 and 20.1 ng L(-1) for strains 2 and 3) revealing differences in sensitivity among the three tested strains of D. magna. Our results suggest that after deltamethrin exposure, the AChE activity responses can be also used as a biomarker of susceptibility (i.e., variation of strain specific response). Moreover, our results show that strain 1 is the less sensitive in terms of IC50-48 h of AChE, whereas it became the most sensitive when considering the EC50-48 h estimated in the standard ecotoxicity test.

  2. Virtual Screening of Acetylcholinesterase Inhibitors Using the Lipinski's Rule of Five and ZINC Databank

    PubMed Central

    Nogara, Pablo Andrei; Saraiva, Rogério de Aquino; Caeran Bueno, Diones; Lissner, Lílian Juliana; Lenz Dalla Corte, Cristiane; Braga, Marcos M.; Rosemberg, Denis Broock; Rocha, João Batista Teixeira

    2015-01-01

    Alzheimer's disease (AD) is a progressive and neurodegenerative pathology that can affect people over 65 years of age. It causes several complications, such as behavioral changes, language deficits, depression, and memory impairments. One of the methods used to treat AD is the increase of acetylcholine (ACh) in the brain by using acetylcholinesterase inhibitors (AChEIs). In this study, we used the ZINC databank and the Lipinski's rule of five to perform a virtual screening and a molecular docking (using Auto Dock Vina 1.1.1) aiming to select possible compounds that have quaternary ammonium atom able to inhibit acetylcholinesterase (AChE) activity. The molecules were obtained by screening and further in vitro assays were performed to analyze the most potent inhibitors through the IC50 value and also to describe the interaction models between inhibitors and enzyme by molecular docking. The results showed that compound D inhibited AChE activity from different vertebrate sources and butyrylcholinesterase (BChE) from Equus ferus (EfBChE), with IC50 ranging from 1.69 ± 0.46 to 5.64 ± 2.47 µM. Compound D interacted with the peripheral anionic subsite in both enzymes, blocking substrate entrance to the active site. In contrast, compound C had higher specificity as inhibitor of EfBChE. In conclusion, the screening was effective in finding inhibitors of AChE and BuChE from different organisms. PMID:25685814

  3. Extreme storm activity in North Atlantic and European region

    NASA Astrophysics Data System (ADS)

    Vyazilova, N.

    2010-09-01

    The extreme storm activity study over North Atlantic and Europe includes the analyses of extreme cyclone (track number, integral cyclonic intensity) and extreme storm (track number) during winter and summer seasons in the regions: 1) 55°N-80N, 50°W-70°E; 2) 30°N-55°N, 50°W-70°E. Extreme cyclones were selected based on cyclone centre pressure (P<=970 mbar). Extreme storms were selected from extreme cyclones based on wind velocity on 925 mbar. The Bofort scala was used for this goal. Integral cyclonic intensity (for region) includes the calculation cyclone centers number and sum of MSLP anomalies in cyclone centers. The analyses based on automated cyclone tracking algorithm, 6-hourly MSLP and wind data (u and v on 925 gPa) from the NCEP/NCAR reanalyses from January 1948 to March 2010. The comparision of mean, calculated for every ten years, had shown, that in polar region extreme cyclone and storm track number, and integral cyclonic intensity gradually increases and have maximum during last years (as for summer, as for winter season). Every ten years means for summer season are more then for winter season, as for polar, as for tropical region. Means (ten years) for tropical region are significance less then for polar region.

  4. Positive cooperative regulation of double binding sites for human acetylcholinesterase.

    PubMed

    Liu, Hao; Ye, Wei; Chen, Hai-Feng

    2016-10-25

    Acetylcholinesterase is a potent enzyme that regulates neurotransmission by rapidly hydrolyzing the neurotransmitter acetylcholine in synapses of the nervous system. As drug target of anti-AD, it has catalytic and peripheral anionic sites. However, the regulation relation between these two sites is unclear. Therefore, we constructed dynamics fluctuation network based on all-atom molecular dynamics simulations to reveal the regulation mechanism. The results suggest that the correlation network in double-site system (hAChE/TZ5) is distinctly different from that in the free state and single-site systems (hAChE/huprine and hAChE/1YL). The community network analysis indicates that the information freely transfers from the peripheral anionic site to the catalytic active site in hAChE/TZ5. Furthermore, the binding free energy between the inhibitor and hAChE for hAChE/TZ5 is significantly lower than of either hAChE/huprine or hAChE/1YL. Thus, a hypothesis of 'positive cooperative regulation' is proposed for the regulation of double binding sites and further confirmed by the weakening and mutation community analyses. Finally, one possible cooperative regulation pathway of W86-TZ5-W286 was identified based on the shortest path algorithm and was confirmed by the network perturbation analysis. Interestingly, the regulation pathway for single-site systems is significantly different from that of dual-site system. The process targeting on the shortest pathway can better regulate the hydrolyzing the neurotransmitter acetylcholine and significantly inhibit the aggregation of Aβ amyloid.

  5. Effect of local acetylcholinesterase inhibition on sweat rate in humans

    NASA Technical Reports Server (NTRS)

    Shibasaki, M.; Crandall, C. G.

    2001-01-01

    ACh is the neurotransmitter responsible for increasing sweat rate (SR) in humans. Because ACh is rapidly hydrolyzed by acetylcholinesterase (AChE), it is possible that AChE contributes to the modulation of SR. Thus the primary purpose of this project was to identify whether AChE around human sweat glands is capable of modulating SR during local application of various concentrations of ACh in vivo, as well as during a heat stress. In seven subjects, two microdialysis probes were placed in the intradermal space of the forearm. One probe was perfused with the AChE inhibitor neostigmine (10 microM); the adjacent membrane was perfused with the vehicle (Ringer solution). SR over both membranes was monitored via capacitance hygrometry during microdialysis administration of various concentrations of ACh (1 x 10(-7)-2 M) and during whole body heating. SR was significantly greater at the neostigmine-treated site than at the control site during administration of lower concentrations of ACh (1 x 10(-7)-1 x 10(-3) M, P < 0.05), but not during administration of higher concentrations of ACh (1 x 10(-2)-2 M, P > 0.05). Moreover, the core temperature threshold for the onset of sweating at the neostigmine-treated site was significantly reduced relative to that at the control site. However, no differences in SR were observed between sites after 35 min of whole body heating. These results suggest that AChE is capable of modulating SR when ACh concentrations are low to moderate (i.e., when sudomotor activity is low) but is less effective in governing SR after SR has increased substantially.

  6. PATTERNS OF ACTIVITY IN A GLOBAL MODEL OF A SOLAR ACTIVE REGION

    SciTech Connect

    Bradshaw, S. J.; Viall, N. M. E-mail: Nicholeen.M.Viall@nasa.gov

    2016-04-10

    In this work we investigate the global activity patterns predicted from a model active region heated by distributions of nanoflares that have a range of frequencies. What differs is the average frequency of the distributions. The activity patterns are manifested in time lag maps of narrow-band instrument channel pairs. We combine hydrodynamic and forward modeling codes with a magnetic field extrapolation to create a model active region and apply the time lag method to synthetic observations. Our aim is not to reproduce a particular set of observations in detail, but to recover some typical properties and patterns observed in active regions. Our key findings are the following. (1) Cooling dominates the time lag signature and the time lags between the channel pairs are generally consistent with observed values. (2) Shorter coronal loops in the core cool more quickly than longer loops at the periphery. (3) All channel pairs show zero time lag when the line of sight passes through coronal loop footpoints. (4) There is strong evidence that plasma must be re-energized on a timescale comparable to the cooling timescale to reproduce the observed coronal activity, but it is likely that a relatively broad spectrum of heating frequencies are operating across active regions. (5) Due to their highly dynamic nature, we find nanoflare trains produce zero time lags along entire flux tubes in our model active region that are seen between the same channel pairs in observed active regions.

  7. Armenia as a Regional Centre for Astronomy for Development activities

    NASA Astrophysics Data System (ADS)

    Mickaelian, A.

    2015-03-01

    The Byurakan Astrophysical Observatory (BAO, Armenia, http://www.bao.am) are among the candidate IAU Regional Nodes for Astronomy for Development activities. It is one of the main astronomical centers of the former Soviet Union and the Middle East region. At present there are 48 qualified researchers at BAO, including six Doctors of Science and 30 PhDs. Five important observational instruments are installed at BAO, the larger ones being 2.6m Cassegrain (ZTA-2.6) and 1m Schmidt (the one that provided the famous Markarian survey). BAO is regarded as a national scientific-educational center, where a number of activities are being organized, such as: international conferences (4 IAU symposia and 1 IAU colloquium, JENAM-2007, etc.), small workshops and discussions, international summer schools (1987, 2006, 2008 and 2010), and Olympiads. BAO collaborates with scientists from many countries. The Armenian Astronomical Society (ArAS, http://www.aras.am/) is an NGO founded in 2001; it has 93 members and it is rather active in the organization of educational, amateur, popular, promotional and other matters. The Armenian Virtual Observatory (ArVO, http://www.aras.am/Arvo/arvo.htm) is one of the 17 national VO projects forming the International Virtual Observatories Alliance (IVOA) and is the only VO project in the region serving also for educational purposes. A number of activities are planned, such as management, coordination and evaluation of the IAU programs in the area of development and education, establishment of the new IAU endowed lectureship program and organization of seminars and public lectures, coordination and initiation of fundraising activities for astronomy development, organization of regional scientific symposia, conferences and workshops, support to Galileo Teacher Training Program (GTTP), production/publication of educational and promotional materials, etc.

  8. Active region upflows. I. Multi-instrument observations

    NASA Astrophysics Data System (ADS)

    Vanninathan, K.; Madjarska, M. S.; Galsgaard, K.; Huang, Z.; Doyle, J. G.

    2015-12-01

    Context. We study upflows at the edges of active regions, called AR outflows, using multi-instrument observations. Aims: This study intends to provide the first direct observational evidence of whether chromospheric jets play an important role in furnishing mass that could sustain coronal upflows. The evolution of the photospheric magnetic field, associated with the footpoints of the upflow region and the plasma properties of active region upflows is investigated with the aim of providing information for benchmarking data-driven modelling of this solar feature. Methods: We spatially and temporally combine multi-instrument observations obtained with the Extreme-ultraviolet Imaging Spectrometer on board the Hinode, the Atmospheric Imaging Assembly and the Helioseismic Magnetic Imager instruments on board the Solar Dynamics Observatory and the Interferometric BI-dimensional Spectro-polarimeter installed at the National Solar Observatory, Sac Peak, to study the plasma parameters of the upflows and the impact of the chromosphere on active region upflows. Results: Our analysis shows that the studied active region upflow presents similarly to those studied previously, i.e. it displays blueshifted emission of 5-20 kms-1 in Fe xii and Fe xiii and its average electron density is 1.8 × 109 cm-3 at 1 MK. The time variation of the density is obtained showing no significant change (in a 3σ error). The plasma density along a single loop is calculated revealing a drop of 50% over a distance of ~20 000 km along the loop. We find a second velocity component in the blue wing of the Fe xii and Fe xiii lines at 105 kms-1 reported only once before. For the first time we study the time evolution of this component at high cadence and find that it is persistent during the whole observing period of 3.5 h with variations of only ±15 kms-1. We also, for the first time, study the evolution of the photospheric magnetic field at high cadence and find that magnetic flux diffusion is

  9. A Mechanism-based 3D-QSAR Approach for Classification and Prediction of Acetylcholinesterase Inhibitory Potency of Organophosphate and Carbamate Analogs

    EPA Science Inventory

    Organophosphate (OP) and carbamate esters can inhibit acetylcholinesterase (AChE) by binding covalently to a serine residue in the enzyme active site, and their inhibitory potency depends largely on affinity for the enzyme and the reactivity of the ester. Despite this understandi...

  10. Coronal Jets from Minifilament Eruptions in Active Regions

    NASA Technical Reports Server (NTRS)

    Martinez, Francisco; Sterling, Alphonse C.; Falconer, David A.; Moore, Ronald L.

    2016-01-01

    Solar coronal jets are transient (frequently of lifetime approx.10 min) features that shoot out from near the solar surface, become much longer than their width, and occur in all solar regions, including coronal holes, quiet Sun, and active regions (e.g., Shimojo et al. 1996, Cirtain et al. 2007). Sterling et al. (2015) and other studies found that in coronal holes and in quiet Sun the jets result when small-scale filaments, called "minifilaments" erupt onto nearby open or high-reaching field lines. Additional studies found that coronal-jet-onset locations (and hence presumably the minifilament-eruption-onset locations) coincided with locations of magnetic-flux cancelation. For active region (AR) jets however the situation is less clear. Sterling et al. (2016) studied jets in one active region over a 24-hour period; they found that some AR jets indeed resulted from minifilament eruptions, usually originating from locations of episodes of magnetic-flux cancelation. In some cases however they could not determine whether flux was emerging or canceling at the polarity inversion line from which the minifilament erupted, and for other jets of that region minifilaments were not conclusively apparent prior to jet occurrence. Here we further study AR jets, by observing them in a single AR over a one-week period, using X-ray images from Hinode/XRT and EUV/UV images from SDO/AIA, and line-of-sight magnetograms and white-light intensity-grams from SDO/HMI. We initially identified 13 prominent jets in the XRT data, and examined corresponding AIA and HMI data. For at least several of the jets, our findings are consistent with the jets resulting from minifilament eruptions, and originating from sites of magnetic-field cancelation.

  11. Physical Properties of Cooling Plasma in Quiescent Active Region Loops

    NASA Astrophysics Data System (ADS)

    Landi, E.; Miralles, M. P.; Curdt, W.; Hara, H.

    2009-04-01

    In the present work, we use SOHO/SUMER, SOHO/UVCS, SOHO/EIT, SOHO/LASCO, STEREO/EUVI, and Hinode/EIS coordinated observations of an active region (AR 10989) at the west limb taken on 2008 April 8 to study the cooling of coronal loops. The cooling plasma is identified using the intensities of SUMER spectral lines emitted at temperatures in the 4.15 <= log T <= 5.45 range. EIS and SUMER spectral observations are used to measure the physical properties of the loops. We found that before cooling took place these loops were filled with coronal hole-like plasma, with temperatures in the 5.6 <= log T <= 5.9 range. SUMER spectra also allowed us to determine the plasma temperature, density, emission measure, element abundances, and dynamic status during the cooling process. The ability of EUVI to observe the emitting region from a different direction allowed us to measure the volume of the emitting region and estimate its emission measure. Comparison with values measured from line intensities provided us with an estimate of the filling factor. UVCS observations of the coronal emission above the active region showed no streamer structure associated with AR 10989 at position angles between 242°and 253fdg EIT, LASCO, and EUVI-A narrowband images and UVCS spectral observations were used to discriminate between different scenarios and monitor the behavior of the active region in time. The present study provides the first detailed measurements of the physical properties of cooling loops, a very important benchmark for theoretical models of loop cooling and condensation.

  12. In silico pharmacophore model for tabun-inhibited acetylcholinesterase reactivators: a study of their stereoelectronic properties.

    PubMed

    Bhattacharjee, Apurba K; Kuca, Kamil; Musilek, Kamil; Gordon, Richard K

    2010-01-01

    Organophosphorus (OP) nerve agents that inhibit acetylcholinesterase (AChE; EC 3.1.1.7) function in the nervous system, causing acute intoxication. If untreated, death can result. Inhibited AChE can be reactivated by oximes, antidotes for OP exposure. However, OP intoxication caused by the nerve agent tabun (GA) is particularly resistant to oximes, which poorly reactivate GA-inhibited AChE. In an attempt to develop a rational strategy for the discovery and design of novel reactivators with lower toxicity and increased efficacy in reactivating GA-inhibited AChE, we developed the first in silico pharmacophore model for binding affinity of GA-inhibited AChE from a set of 11 oximes. Oximes were analyzed for stereoelectronic profiles and three-dimensional quantitative structure-activity relationship pharmacophores using ab initio quantum chemical and pharmacophore generation methods. Quantum chemical methods were sequentially used from semiempirical AM1 to hierarchical ab initio calculations to determine the stereoelectronic properties of nine oximes exhibiting affinity for binding to GA-inhibited AChE in vivo. The calculated stereoelectronic properties led us to develop the in silico pharmacophore model using CATALYST methodology. Specific stereoelectronic profiles including the distance between bisquarternary nitrogen atoms of the pyridinium ring in the oximes, hydrophilicity, surface area, nucleophilicity of the oxime oxygen, and location of the molecular orbitals on the isosurfaces have important roles for potencies for reactivating GA-inhibited AChE. The in silico pharmacophore model of oxime affinity for binding to GA-inhibited AChE was found to require a hydrogen bond acceptor, a hydrogen bond donor at the two terminal regions, and an aromatic ring in the central region of the oximes. The model was found to be well-correlated (R = 0.9) with experimental oxime affinity for binding to GA-inhibited AChE. Additional stereoelectronic features relating activity with

  13. Acetylcholinesterase Inhibition by Biofumigant (Coumaran) from Leaves of Lantana camara in Stored Grain and Household Insect Pests

    PubMed Central

    Raghavendra, Anjanappa; Bakthavatsalam, Nandagopal

    2014-01-01

    Recent studies proved that the biofumigants could be an alternative to chemical fumigants against stored grain insect pests. For this reason, it is necessary to understand the mode of action of biofumigants. In the present study the prospectus of utilising Lantana camara as a potent fumigant insecticide is being discussed. Inhibition of acetylcholinesterase (AChE) by Coumaran, an active ingredient extracted from the plant L. camara, was studied. The biofumigant was used as an enzyme inhibitor and acetylthiocholine iodide as a substrate along with Ellman's reagent to carry out the reactions. The in vivo inhibition was observed in both dose dependent and time dependent in case of housefly, and the nervous tissue (ganglion) and the whole insect homogenate of stored grain insect exposed to Coumaran. The possible mode of action of Coumaran as an acetylcholinesterase inhibitor is discussed. PMID:25025036

  14. Acetylcholinesterase inhibition by biofumigant (Coumaran) from leaves of Lantana camara in stored grain and household insect pests.

    PubMed

    Rajashekar, Yallappa; Raghavendra, Anjanappa; Bakthavatsalam, Nandagopal

    2014-01-01

    Recent studies proved that the biofumigants could be an alternative to chemical fumigants against stored grain insect pests. For this reason, it is necessary to understand the mode of action of biofumigants. In the present study the prospectus of utilising Lantana camara as a potent fumigant insecticide is being discussed. Inhibition of acetylcholinesterase (AChE) by Coumaran, an active ingredient extracted from the plant L. camara, was studied. The biofumigant was used as an enzyme inhibitor and acetylthiocholine iodide as a substrate along with Ellman's reagent to carry out the reactions. The in vivo inhibition was observed in both dose dependent and time dependent in case of housefly, and the nervous tissue (ganglion) and the whole insect homogenate of stored grain insect exposed to Coumaran. The possible mode of action of Coumaran as an acetylcholinesterase inhibitor is discussed.

  15. Electric currents and coronal heating in NOAA active region 6952

    NASA Technical Reports Server (NTRS)

    Metcalf, T. R.; Canfield, R. C.; Hudson, H. S.; Mickey, D. L.; Wulser, J. -P.; Martens, P. C. H.; Tsuneta, S.

    1994-01-01

    We examine the spatial and temporal relationship between coronal structures observed with the soft X-ray telescope (SXT) on board the Yohkoh spacecraft and the vertical electric current density derived from photospheric vector magnetograms obtained using the Stokes Polarimeter at the Mees Solar Observatory. We focus on a single active region: AR 6952 which we observed on 7 days during 1991 December. For 11 independent maps of the vertical electric current density co-aligned with non-flaring X-ray images, we search for a morphological relationship between sites of high vertical current density in the photosphere and enhanced X-ray emission in the overlying corona. We find no compelling spatial or temporal correlation between the sites of vertical current and the bright X-ray structures in this active region.

  16. Evidence of active region imprints on the solar wind structure

    NASA Technical Reports Server (NTRS)

    Hick, P.; Jackson, B. V.

    1995-01-01

    A common descriptive framework for discussing the solar wind structure in the inner heliosphere uses the global magnetic field as a reference: low density, high velocity solar wind emanates from open magnetic fields, with high density, low speed solar wind flowing outward near the current sheet. In this picture, active regions, underlying closed magnetic field structures in the streamer belt, leave little or no imprint on the solar wind. We present evidence from interplanetary scintillation measurements of the 'disturbance factor' g that active regions play a role in modulating the solar wind and possibly contribute to the solar wind mass output. Hence we find that the traditional view of the solar wind, though useful in understanding many features of solar wind structure, is oversimplified and possibly neglects important aspects of solar wind dynamics

  17. Modeling the Subsurface Evolution of Active-Region Flux Tubes

    NASA Astrophysics Data System (ADS)

    Fan, Y.

    2009-12-01

    I present results from a set of 3-D spherical-shell MHD simulations of the buoyant rise of active region flux tubes in the solar interior that put new constraints on the initial twist of the subsurface tubes in order for them to emerge with tilt angles consistent with the observed Joy's law for the mean tilt of solar active regions. Due to asymmetric stretching of the Ω-shaped tube by the Coriolis force, a field strength asymmetry develops with the leading side having a greater field strength and thus being more cohesive compared to the following side. Furthermore, the magnetic flux in the leading leg shows more coherent values of local twist α ≡ JB / B2, whereas the values in the following leg show large fluctuations and are of mixed signs.

  18. Regional Blood-Brain Barrier Responses to Central Cholinergic Activity

    DTIC Science & Technology

    1989-07-30

    regions were of particular interest because they show the largest decreases in glucose metabolism following limbic seizures ( Ben - Ari et al., 1981). It is...following seizures ( Ben - Ari et. al., 1981). The piriform cortex-amygdala also appears to be a generator of epileptiform activity in a variety of seizure...produced by PTZ. Such studies are ongoing and the results will be given in subsequent reports. 11 REFERENCES Ben - Ari , Y., D. Richie, E. Tremblay and G

  19. Multi-wavelength Observations of Microflares Near an Active Region

    NASA Astrophysics Data System (ADS)

    Bein, B.; Veronig, A.; Rybak, J.; Gömöry, P.; Berkebile-Stoiser, S.; Sütterlin, P.

    We study the multi-wavelength characteristics of a microflaring active region (AR 10898) near disc centre. The analysed data were from the 4^{th} of July 2006, and were recorded by DOT (Hα, Ca II H), RHESSI (X-rays), TRACE (EUV) and SOHO/MDI (magnetograms). The identified microflare events were studied with respect to their magnetic field configuration and their multi-wavelength time evolution.

  20. Preclinical and first-in-human evaluation of PRX-105, a PEGylated, plant-derived, recombinant human acetylcholinesterase-R.

    PubMed

    Atsmon, Jacob; Brill-Almon, Einat; Nadri-Shay, Carmit; Chertkoff, Raul; Alon, Sari; Shaikevich, Dimitri; Volokhov, Inna; Haim, Kirsten Y; Bartfeld, Daniel; Shulman, Avidor; Ruderfer, Ilya; Ben-Moshe, Tehila; Shilovitzky, Orit; Soreq, Hermona; Shaaltiel, Yoseph

    2015-09-15

    PRX-105 is a plant-derived recombinant version of the human 'read-through' acetylcholinesterase splice variant (AChE-R). Its active site structure is similar to that of the synaptic variant, and it displays the same affinity towards organophosphorus (OP) compounds. As such, PRX-105 may serve as a bio-scavenger for OP pesticides and chemical warfare agents. To assess its potential use in prophylaxis and treatment of OP poisoning we conducted several preliminary tests, reported in this paper. Intravenous (IV) PRX-105 was administered to mice either before or after exposure to an OP toxin. All mice who received an IV dose of 50nmol/kg PRX-105, 2min before being exposed to 1.33×LD50 and 1.5×LD50 of toxin and 10min after exposure to 1.5×LD50 survived. The pharmacokinetic and toxicity profiles of PRX-105 were evaluated in mice and mini-pigs. Following single and multiple IV doses (50 to 200mg/kg) no deaths occurred and no significant laboratory and histopathological changes were observed. The overall elimination half-life (t½) in mice was 994 (±173) min. Additionally, a first-in-human study, to assess the safety, tolerability and pharmacokinetics of the compound, was conducted in healthy volunteers. The t½ in humans was substantially longer than in mice (average 26.7h). Despite the small number of animals and human subjects who were assessed, the fact that PRX-105 exerts a protective and therapeutic effect following exposure to lethal doses of OP, its favorable safety profile and its relatively long half-life, renders it a promising candidate for treatment and prophylaxis against OP poisoning and warrants further investigation.

  1. A Survey of Nanoflare Properties in Solar Active Regions

    NASA Astrophysics Data System (ADS)

    Viall, N. M.; Klimchuk, J. A.

    2013-12-01

    We investigate coronal heating using a systematic technique to analyze the properties of nanoflares in active regions (AR). Our technique computes cooling times, or time-lags, on a pixel-by-pixel basis using data taken with the Atmospheric Imaging Assembly onboard the Solar Dynamics Observatory. Our technique has the advantage that it allows us to analyze all of the coronal AR emission, including the so-called diffuse emission. We recently presented results using this time-lag analysis on NOAA AR 11082 (Viall & Klimchuk 2012) and found that the majority of the pixels contained cooling plasma along their line of sight, consistent with impulsive coronal nanoflare heating. Additionally, our results showed that the nanoflare energy is stronger in the AR core and weaker in the active region periphery. Are these results representative of the nanoflare properties exhibited in the majority of ARs, or is AR 11082 unique? Here we present the time-lag results for a survey of ARs and show that these nanoflare patterns are born out in other active regions, for a range of ages, magnetic complexity, and total unsigned magnetic flux. Other aspects of the nanoflare properties, however, turn out to be dependent on certain AR characteristics.

  2. The Intermediate-line Region in Active Galactic Nuclei

    NASA Astrophysics Data System (ADS)

    Adhikari, T. P.; Różańska, A.; Czerny, B.; Hryniewicz, K.; Ferland, G. J.

    2016-11-01

    We show that the recently observed suppression of the gap between the broad-line region (BLR) and the narrow-line region (NLR) in some active galactic nuclei (AGNs) can be fully explained by an increase of the gas density in the emitting region. Our model predicts the formation of the intermediate-line region (ILR) that is observed in some Seyfert galaxies by the detection of emission lines with intermediate-velocity FWHM ˜ 700-1200 km s-1. These lines are believed to be originating from an ILR located somewhere between the BLR and NLR. As was previously proved, the apparent gap is assumed to be caused by the presence of dust beyond the sublimation radius. Our computations with the use of the cloudy photoionization code show that the differences in the shape of the spectral energy distribution from the central region of AGNs do not diminish the apparent gap in the line emission in those objects. A strong discontinuity in the line emission versus radius exists for all lines at the dust sublimation radius. However, increasing the gas density to ˜{10}11.5 cm-3 at the sublimation radius provides the continuous line emission versus radius and fully explains the recently observed lack of apparent gap in some AGNs. We show that such a high density is consistent with the density of upper layers of an accretion disk atmosphere. Therefore, the upper layers of the disk atmosphere can give rise to the formation of observed emission-line clouds.

  3. Holocene fire activity in the Carpathian region: regional climate vs. local controls

    NASA Astrophysics Data System (ADS)

    Florescu, Gabriela; Feurdean, Angelica

    2015-04-01

    Introduction. Fire drives significant changes in ecosystem structure and function, diversity, species evolution, biomass dynamics and atmospheric composition. Palaeodata and model-based studies have pointed towards a strong connection between fire activity, climate, vegetation and people. Nevertheless, the relative importance of these factors appears to be strongly variable and a better understanding of these factors and their interaction needs a thorough investigation over multiple spatial (local to global) and temporal (years to millennia) scales. In this respect, sedimentary charcoal, associated with other proxies of climate, vegetation and human impact, represents a powerful tool of investigating changes in past fire activity, especially in regions with scarce fire dataset such as the CE Europe. Aim. To increase the spatial and temporal coverage of charcoal records and facilitate a more critical examination of the patterns, drivers and consequences of biomass burning over multiple spatial and temporal scales in CE Europe, we have investigated 6 fossil sequences in the Carpathian region (northern Romania). These are located in different geographical settings, in terms of elevation, vegetation composition, topography and land-use. Specific questions are: i) determine trends in timing and magnitude of fire activity, as well as similarities and differences between elevations; ii) disentangle the importance of regional from local controls in fire activity; iii) evaluate ecological consequences of fire on landscape composition, structure and diversity. Methods. We first determine the recent trends in fire activity (the last 150 years) from charcoal data and compare them with instrumental records of temperature, precipitation, site history and topography for a better understanding of the relationship between sedimentary charcoal and historical fire activity. We then statistically quantify centennial to millennial trends in fire activity (frequency, magnitude) based on

  4. Monitoring rice farming activities in the Mekong Delta region

    NASA Astrophysics Data System (ADS)

    Nguyen, S. T.; Chen, C. F.; Chen, C. R.; Chiang, S. H.; Chang, L. Y.; Khin, L. V.

    2015-12-01

    Half of the world's population depends on rice for survival. Rice agriculture thus plays an important role in the developing world's economy. Vietnam is one of the largest rice producers and suppliers on earth and more than 80% of the exported rice was produced from the Mekong Delta region, which is situated in the southwestern Vietnam and encompasses approximately 40,000 km2. Changes in climate conditions could likely trigger the increase of insect populations and rice diseases, causing the potential loss of rice yields. Monitoring rice-farming activities through crop phenology detection can provide policymakers with timely strategies to mitigate possible impacts on the potential yield as well as rice grain exports to ensure food security for the region. The main objective of this study is to develop a logistic-based algorithm to investigate rice sowing and harvesting activities from the multi-temporal Moderate Resolution Imaging Spectroradiometer (MODIS)-Landsat fusion data. We processed the data for two main cropping seasons (i.e., winter-spring and summer-autumn seasons) through a three-step procedure: (1) MODIS-Landsat data fusion, (2) construction of the time-series enhanced vegetation index 2 (EVI2) data, (3) rice crop phenology detection. The EVI2 data derived from the fusion results between MODIS and Landsat data were compared with that of Landsat data indicated close correlation between the two datasets (R2 = 0.93). The time-series EVI2 data were processed using the double logistic method to detect the progress of sowing and harvesting activities in the region. The comparisons between the estimated sowing and harvesting dates and the field survey data revealed the root mean squared error (RMSE) values of 8.4 and 5.5 days for the winter-spring crop and 9.4 and 12.8 days for the summer-autumn crop, respectively. This study demonstrates the effectiveness of the double logistic-based algorithm for rice crop monitoring from temporal MODIS-Landsat fusion data

  5. Density and Temperature Measurements in a Solar Active Region

    NASA Astrophysics Data System (ADS)

    Warren, Harry P.; Winebarger, Amy R.

    2003-10-01

    We present electron density and temperature measurements from an active region observed above the limb with the Solar Ultraviolet Measurements of Emitted Radiation spectrometer on the Solar and Heliospheric Observatory. Density-sensitive line ratios from Si VIII and S X indicate densities greater than 108 cm-3 as high as 200" (or 145 Mm) above the limb. At these heights, static, uniformly heated loop models predict densities close to 107 cm-3. Differential emission measure analysis shows that the observed plasma is nearly isothermal with a mean temperature of about 1.5 MK and a dispersion of about 0.2 MK. Both the differential emission measure and the Si XI/Si VIII line ratios indicate only small variations in the temperature at the heights observed. These measurements confirm recent observations from the Transition Region and Coronal Explorer of ``overdense'' plasma at temperatures near 1 MK in solar active regions. Time-dependent hydrodynamic simulations suggest that impulsive heating models can account for the large densities, but they have a difficult time reproducing the narrow range of observed temperatures. The observations of overdense, nearly isothermal plasma in the solar corona provide a significant challenge to theories of coronal heating.

  6. FORMATION OF CORONAL HOLES ON THE ASHES OF ACTIVE REGIONS

    SciTech Connect

    Karachik, Nina V.; Pevtsov, Alexei A.; Abramenko, Valentyna I. E-mail: apevtsov@nso.ed

    2010-05-10

    We investigate the formation of isolated non-polar coronal holes (CHs) on the remnants of decaying active regions (ARs) at the minimum/early ascending phase of sunspot activity. We follow the evolution of four bipolar ARs and measure several parameters of their magnetic fields including total flux, imbalance, and compactness. As regions decay, their leading and following polarities exhibit different dissipation rates: loose polarity tends to dissipate faster than compact polarity. As a consequence, we see a gradual increase in flux imbalance inside a dissipating bipolar region, and later a formation of a CH in place of more compact magnetic flux. Out of four cases studied in detail, two CHs had formed at the following polarity of the decaying bipolar AR, and two CHs had developed in place of the leading polarity field. All four CHs contain a significant fraction of magnetic field of their corresponding AR. Using potential field extrapolation, we show that the magnetic field lines of these CHs were closed on the polar CH at the North, which at the time of the events was in imbalance with the polar CH at the South. This topology suggests that the observed phenomenon may play an important role in transformation of toroidal magnetic field to poloidal field, which is a key step in transitioning from an old solar cycle to a new one. The timing of this observed transition may indicate the end of solar cycle 23 and the beginning of cycle 24.

  7. Active Region Oscillations: Results from SOHO JOP 097

    NASA Astrophysics Data System (ADS)

    O'Shea, E.; Fleck, B.; Muglach, K.; Sütterlin, P.

    2001-05-01

    We present here an analysis of data obtained in a sunspot region, using the Coronal Diagnostic Spectrometer (CDS) on SOHO. These data were obtained in the context of the Joint Observing Program (JOP) 97 which, together with CDS, included the Michelson Doppler Imaging (MDI) instrument on SOHO, the TRACE satellite and various ground based observatories, e.g. the DOT on La Palma. Using the lines of Fe XVI 335, Mg IX 368, He I 584, O III 599, Mg X 624 and O V 624 of CDS time series data were obtained in the pore and plage regions of sunspots associated with active regions AR 9166, 9166 and 9169 between September 19-29 2000. In addition to the time series datasets we also obtained 240 arcsec x 240 arcsec raster images of the sunspot regions examined. Using different time series analysis techniques we analyse the different periods of oscillation found in time series datasets and present the results here. This research is part of the European Solar Magnetometry Network supported by the EC through the TMR programme.

  8. Helioseismology of pre-emerging active regions. III. Statistical analysis

    SciTech Connect

    Barnes, G.; Leka, K. D.; Braun, D. C.; Birch, A. C.

    2014-05-01

    The subsurface properties of active regions (ARs) prior to their appearance at the solar surface may shed light on the process of AR formation. Helioseismic holography has been applied to samples taken from two populations of regions on the Sun (pre-emergence and without emergence), each sample having over 100 members, that were selected to minimize systematic bias, as described in Paper I. Paper II showed that there are statistically significant signatures in the average helioseismic properties that precede the formation of an AR. This paper describes a more detailed analysis of the samples of pre-emergence regions and regions without emergence based on discriminant analysis. The property that is best able to distinguish the populations is found to be the surface magnetic field, even a day before the emergence time. However, after accounting for the correlations between the surface field and the quantities derived from helioseismology, there is still evidence of a helioseismic precursor to AR emergence that is present for at least a day prior to emergence, although the analysis presented cannot definitively determine the subsurface properties prior to emergence due to the small sample sizes.

  9. Structural evidence that human acetylcholinesterase inhibited by tabun ages through O-dealkylation.

    PubMed

    Carletti, Eugénie; Colletier, Jacques-Philippe; Dupeux, Florine; Trovaslet, Marie; Masson, Patrick; Nachon, Florian

    2010-05-27

    Tabun is a warfare agent that inhibits human acetylcholinesterase (hAChE) by rapid phosphylation of the catalytic serine. A time-dependent reaction occurs on the tabun adduct, leading to an "aged" enzyme, resistant to oxime reactivators. The aging reaction may proceed via either dealkylation or deamidation, depending on the stereochemistry of the phosphoramidyl adduct. We solved the X-ray structure of aged tabun-hAChE complexed with fasciculin II, and we show that aging proceeds through O-dealkylation, in agreement with the aging mechanism that we determined for tabun-inhibited human butyrylcholinesterase and mouse acetylcholinesterase. Noteworthy, aging and binding of fasciculin II lead to an improved thermostability, resulting from additional stabilizing interactions between the two subdomains that face each other across the active site gorge. This first structure of hAChE inhibited by a nerve agent provides structural insight into the inhibition and aging mechanisms and a structural template for the design of molecules capable of reactivating aged hAChE.

  10. Anatomy of acetylcholinesterase catalysis: reaction dynamics analogy for human erythrocyte and electric eel enzymes.

    PubMed

    Acheson, S A; Quinn, D M

    1990-09-03

    The anatomy of catalysis (i.e., reaction dynamics, thermodynamics and transition state structures) is compared herein for acetylcholinesterases from human erythrocytes and Electrophorus electricus. The two enzymes have similar relative activities for the substrate o-nitrochloroacetanilide and o-nitrophenyl acetate. In addition, with each substrate K values and solvent deuterium kinetic isotope effects for kES and kE are similar for the two enzymes. Solvent isotope effects in mixed isotopic buffers indicate that the acylation stages of o-nitrochloroacetanilide turnover by the two enzymes are rate-limited by virtual transition states that are weighted averages of contributions from transition states of serial chemical and physical steps. Similar experiments show that the transition states for Vmax of o-nitrophenyl acetate turnover by the two enzymes are stabilized by simple general acid-base (i.e., one-proton) catalysis. These comparisons demonstrate that acetylcholinesterases from diverse sources display functional analogy in that reaction dynamics and transition state structures are closely similar.

  11. Novel and Viable Acetylcholinesterase Target Site for Developing Effective and Environmentally Safe Insecticides

    PubMed Central

    Pang, Yuan-Ping; Brimijoin, Stephen; Ragsdale, David W; Zhu, Kun Yan; Suranyi, Robert

    2012-01-01

    Insect pests are responsible for human suffering and financial losses worldwide. New and environmentally safe insecticides are urgently needed to cope with these serious problems. Resistance to current insecticides has resulted in a resurgence of insect pests, and growing concerns about insecticide toxicity to humans discourage the use of insecticides for pest control. The small market for insecticides has hampered insecticide development; however, advances in genomics and structural genomics offer new opportunities to develop insecticides that are less dependent on the insecticide market. This review summarizes the literature data that support the hypothesis that an insect-specific cysteine residue located at the opening of the acetylcholinesterase active site is a promising target site for developing new insecticides with reduced off-target toxicity and low propensity for insect resistance. These data are used to discuss the differences between targeting the insect-specific cysteine residue and targeting the ubiquitous catalytic serine residue of acetylcholinesterase from the perspective of reducing off-target toxicity and insect resistance. Also discussed is the prospect of developing cysteine-targeting anticholinesterases as effective and environmentally safe insecticides for control of disease vectors, crop damage, and residential insect pests within the financial confines of the present insecticide market. PMID:22280344

  12. Photometric observations of the energetics of small solar active regions

    SciTech Connect

    Lawrence, J.K.; Chapman, G.A. )

    1990-10-01

    The energetics of small solar active regions was investigated using for the analysis the photometric solar images taken from July 29 to September 6, 1984 with the San Fernando Observatory's 28-cm vacuum telescope, vacuum spectroheliograph, and dual 512 element Reticon linear diode arrays. Ten small newly formed regions were observed, whose entire sunspot evolution apparently occurred within the observed disk crossing. Seven of these showed a net energy excess of a few times 10 to the 33th ergs during this time. These results are discussed in connection with the 0.1 percent decline in solar irradiance observed by the SMM/ACRIM and Nimbus 7/ERB radiometers between 1980 and 1986. 35 refs.

  13. Multi-wavelength Observations of Solar Active Region NOAA 7154

    NASA Technical Reports Server (NTRS)

    Bruner, M. E.; Nitta, N. V.; Frank. Z. A.; Dame, L.; Suematsu, Y.

    2000-01-01

    We report on observations of a solar active region in May 1992 by the Solar Plasma Diagnostic Experiment (SPDE) in coordination with the Yohkoh satellite (producing soft X-ray images) and ground-based observatories (producing photospheric magnetograms and various filtergrams including those at the CN 3883 A line). The main focus is a study of the physical conditions of hot (T is approximately greater than 3 MK) coronal loops at their foot-points. The coronal part of the loops is fuzzy but what appear to be their footpoints in the transition region down to the photosphere are compact. Despite the morphological similarities, the footpoint emission at 10(exp 5) K is not quantitatively correlated with that at approximately 300 km above the tau (sub 5000) = 1 level, suggesting that the heat transport and therefore magnetic field topology in the intermediate layer is complicated. High resolution imaging observations with continuous temperature coverage are crucially needed.

  14. Influence of the Cardiac Myosin Hinge Region on Contractile Activity

    NASA Astrophysics Data System (ADS)

    Margossian, Sarkis S.; Krueger, John W.; Sellers, James R.; Cuda, Giovanni; Caulfield, James B.; Norton, Paul; Slayter, Henry S.

    1991-06-01

    The participation of cardiac myosin hinge in contractility was investigated by in vitro motility and ATPase assays and by measurements of sarcomere shortening. The effect on contractile activity was analyzed using an antibody directed against a 20-amino acid peptide within the hinge region of myosin. This antibody bound specifically at the hinge at a distance of 55 nm from the S1/S2 junction, was specific to human, dog, and rat cardiac myosins, did not crossreact with gizzard or skeletal myosin, and had no effect on ATPase activity of purified S1 and myofibrils. However, it completely suppressed the movement of actin filaments in in vitro motility assays and reduced active shortening of sarcomeres of skinned cardiac myocytes by half. Suppression of motion by the antihinge antibody may reflect a mechanical constraint imposed by the antibody upon the mobility of the S2 region of myosin. The results suggest that the steps in the mechanochemical energy transduction can be separately influenced through S2.

  15. High Spatial Resolution Fe XII Observations of Solar Active Regions

    NASA Astrophysics Data System (ADS)

    Testa, Paola; De Pontieu, Bart; Hansteen, Viggo

    2016-08-01

    We use UV spectral observations of active regions with the Interface Region Imaging Spectrograph (IRIS) to investigate the properties of the coronal Fe xii 1349.4 Å emission at unprecedented high spatial resolution (˜0.33″). We find that by using appropriate observational strategies (i.e., long exposures, lossless compression), Fe xii emission can be studied with IRIS at high spatial and spectral resolution, at least for high-density plasma (e.g., post-flare loops and active region moss). We find that upper transition region (TR; moss) Fe xii emission shows very small average Doppler redshifts ({v}{{D}} ˜ 3 km s-1) as well as modest non-thermal velocities (with an average of ˜24 km s-1 and the peak of the distribution at ˜15 km s-1). The observed distribution of Doppler shifts appears to be compatible with advanced three-dimensional radiative MHD simulations in which impulsive heating is concentrated at the TR footpoints of a hot corona. While the non-thermal broadening of Fe xii 1349.4 Å peaks at similar values as lower resolution simultaneous Hinode Extreme Ultraviolet Imaging Spectrometer (EIS) measurements of Fe xii 195 Å, IRIS observations show a previously undetected tail of increased non-thermal broadening that might be suggestive of the presence of subarcsecond heating events. We find that IRIS and EIS non-thermal line broadening measurements are affected by instrumental effects that can only be removed through careful analysis. Our results also reveal an unexplained discrepancy between observed 195.1/1349.4 Å Fe xii intensity ratios and those predicted by the CHIANTI atomic database.

  16. THE EXPANSION OF ACTIVE REGIONS INTO THE EXTENDED SOLAR CORONA

    SciTech Connect

    Morgan, Huw; Jeska, Lauren; Leonard, Drew

    2013-06-01

    Advanced image processing of Large Angle and Spectrometric Coronagraph Experiment (LASCO) C2 observations reveals the expansion of the active region closed field into the extended corona. The nested closed-loop systems are large, with an apparent latitudinal extent of 50 Degree-Sign , and expanding to heights of at least 12 R{sub Sun }. The expansion speeds are {approx}10 km s{sup -1} in the AIA/SDO field of view, below {approx}20 km s{sup -1} at 2.3 R{sub Sun }, and accelerate linearly to {approx}60 km s{sup -1} at 5 R{sub Sun }. They appear with a frequency of one every {approx}3 hr over a time period of around three days. They are not coronal mass ejections (CMEs) since their gradual expansion is continuous and steady. They are also faint, with an upper limit of 3% of the brightness of background streamers. Extreme ultraviolet images reveal continuous birth and expansion of hot, bright loops from a new active region at the base of the system. The LASCO images show that the loops span a radial fan-like system of streamers, suggesting that they are not propagating within the main coronal streamer structure. The expanding loops brighten at low heights a few hours prior to a CME eruption, and the expansion process is temporarily halted as the closed field system is swept away. Closed magnetic structures from some active regions are not isolated from the extended corona and solar wind, but can expand to large heights in the form of quiescent expanding loops.

  17. Implications of Special Regions to Conducting Human Activities on Mars

    NASA Astrophysics Data System (ADS)

    Rummel, J. D.; Barlow, N. G.; Beaty, D. W.; Jones, M. A.; Hipkin, V.

    2014-12-01

    A MEPAG Science Analysis Group (SAG) has undertaken an analysis of Special Regions (SR) on Mars—regions where indigenous martian life could exist or where Earth microbes, if introduced, could survive and reproduce. The SR-SAG has considered the impact of SR on future human activities on the martian surface. Human exploration requires access to in-situ resources, some of which may be found in SR. Water and oxygen for ISRU are found in the atmosphere, surface/near-surface ice, hydrated minerals, and perchlorates. Water ice is most abundant at latitudes poleward of ~60 degrees, but polar darkness, cold temperatures, and CO2 degassing present hazards to human operations in these regions. Accessible water is more limited toward the equator, though temperature and solar energy conditions become more favorable. The possible presence of liquid water in Recurring Slope Lineae and active gullies leads to their treatment as SR. Fuel for surface operations and propellants for crew ascent could be manufactured from the martian atmosphere and surface materials, but dust in the atmosphere may clog ISRU equipment and perchlorate is toxic to humans. Power may be produced from solar or nuclear energy. Reliance on solar energy limits operations to the equatorial zone where easily accessible ice resources are limited. Nuclear power allows surface operations at a range of latitudes, but waste heat could convert some non-SR into SR. Radiation shielding is necessary for long-term human operations on Mars and could be obtained by deposition of regolith or by water storage in tanks or as ice around habitats, or the use of underground habitats. SR-SAG recognizes that it will be impossible for all human-associated processes and operations to be conducted within entirely closed systems. Protocols need to be established so (1) human missions to Mars will not contaminate SR nor be contaminated by materials from them, and (2) human activities on Mars will avoid converting areas into SR.

  18. Temporal evolution of continental lithospheric strength in actively deforming regions

    USGS Publications Warehouse

    Thatcher, W.; Pollitz, F.F.

    2008-01-01

    It has been agreed for nearly a century that a strong, load-bearing outer layer of earth is required to support mountain ranges, transmit stresses to deform active regions and store elastic strain to generate earthquakes. However the dept and extent of this strong layer remain controversial. Here we use a variety of observations to infer the distribution of lithospheric strength in the active western United States from seismic to steady-state time scales. We use evidence from post-seismic transient and earthquake cycle deformation reservoir loading glacio-isostatic adjustment, and lithosphere isostatic adjustment to large surface and subsurface loads. The nearly perfectly elastic behavior of Earth's crust and mantle at the time scale of seismic wave propagation evolves to that of a strong, elastic crust and weak, ductile upper mantle lithosphere at both earthquake cycle (EC, ???10?? to 103 yr) and glacio-isostatic adjustment (GIA, ???103 to 104 yr) time scales. Topography and gravity field correlations indicate that lithosphere isostatic adjustment (LIA) on ???106-107 yr time scales occurs with most lithospheric stress supported by an upper crust overlying a much weaker ductile subtrate. These comparisons suggest that the upper mantle lithosphere is weaker than the crust at all time scales longer than seismic. In contrast, the lower crust has a chameleon-like behavior, strong at EC and GIA time scales and weak for LIA and steady-state deformation processes. The lower crust might even take on a third identity in regions of rapid crustal extension or continental collision, where anomalously high temperatures may lead to large-scale ductile flow in a lower crustal layer that is locally weaker than the upper mantle. Modeling of lithospheric processes in active regions thus cannot use a one-size-fits-all prescription of rheological layering (relation between applied stress and deformation as a function of depth) but must be tailored to the time scale and tectonic

  19. Acetylcholinesterases of blood-feeding flies and ticks.

    PubMed

    Temeyer, Kevin B; Tuckow, Alexander P; Brake, Danett K; Li, Andrew Y; Pérez de León, Adalberto A

    2013-03-25

    Acetylcholinesterase (AChE) is the biochemical target of organophosphate (OP) and carbamate pesticides for invertebrates, vertebrate nerve agents, and AChE inhibitors used to reduce effects of Alzheimer's disease. Organophosphate pesticides (OPs) are widely used to control blood-feeding arthropods, including biting flies and ticks. However, resistance to OPs in pests affecting animal and human health has compromised control efficacy. OP resistance often results from mutations producing an OP-insensitive AChE. Our studies have demonstrated production of OP-insensitive AChEs in biting flies and ticks. Complementary DNA (cDNA) sequences encoding AChEs were obtained for the horn fly, stable fly, sand fly, and the southern cattle tick. The availability of cDNA sequences enables the identification of mutations, expression and characterization of recombinant proteins, gene silencing for functional studies, as well as in vitro screening of novel inhibitors. The southern cattle tick expresses at least three different genes encoding AChE in their synganglion, i.e. brain. Gene amplification for each of the three known cattle tick AChE genes and expression of multiple alleles for each gene may reduce fitness cost associated with OP-resistance. AChE hydrolyzes the neurotransmitter, acetylcholine, but may have additional roles in physiology and development. The three cattle tick AChEs possess significantly different biochemical properties, and are expressed in neural and non-neural tissues, which suggest separation of structure and function. The remarkable complexity of AChEs in ticks suggested by combining genomic data from Ixodes scapularis with our genetic and biochemical data from Rhipicephalus microplus is suggestive of previously unknown gene duplication and diversification. Comparative studies between invertebrate and vertebrate AChEs could enhance our understanding of structure-activity relationships. Research with ticks as a model system offers the opportunity to

  20. Emission Measure Distribution and Heating of Two Active Region Cores

    NASA Technical Reports Server (NTRS)

    Tripathi, Durgesh; Klimchuk, James A.; Mason, Helen E.

    2011-01-01

    Using data from the Extreme-ultraviolet Imaging Spectrometer aboard Hinode, we have studied the coronal plasma in the core of two active regions. Concentrating on the area between opposite polarity moss, we found emission measure distributions having an approximate power-law form EM/T(exp 2.4) from log T = 5.55 up to a peak at log T = 6.57. The observations are explained extremely well by a simple nanoflare model. However, in the absence of additional constraints, the observations could possibly also be explained by steady heating.

  1. Hinode Observations of an Eruption from a Sigmoidal Active Region

    NASA Astrophysics Data System (ADS)

    Green, L. M.; Wallace, A. J.; Kliem, B.

    2012-08-01

    We analyse the evolution of a bipolar active region which produces an eruption during its decay phase. The soft X-ray arcade develops high shear over a time span of two days and transitions to sigmoidal shortly before the eruption. We propose that the continuous sigmoidal soft X-ray threads indicate that a flux rope has formed which is lying low in the solar atmosphere with a bald patch separatrix surface topology. The formation of the flux rope is driven by the photospheric evolution which is dominated by fragmentation of the main polarities, motion due to supergranular flows and cancellation at the polarity inversion line.

  2. SOI/MDI studies of active region seismology and evolution

    NASA Technical Reports Server (NTRS)

    Tarbell, Ted D.; Title, Alan; Hoeksema, J. Todd; Scherrer, Phil; Zweibel, Ellen

    1995-01-01

    The solar oscillations investigation (SOI) will study solar active regions using both helioseismic and conventional observation techniques. The Michelson Doppler imager (MDI) can perform Doppler continuum and line depth imagery and can produce longitudinal magnetograms, showing either the full disk or a high resolution field of view. A dynamics program of continuous full disk Doppler observations for two months per year, campaign programs of eight hours of continuous observation per day, and a synoptic magnetic program of about 15 full disk magnetograms per day, are planned. The scientific plans, measurements and observation programs, are described.

  3. Substrate-emitting semiconductor laser with a trapezoidal active region

    SciTech Connect

    Dikareva, N V; Nekorkin, S M; Karzanova, M V; Zvonkov, B N; Aleshkin, V Ya; Dubinov, A A; Afonenko, A A

    2014-04-28

    Semiconductor lasers with a narrow (∼2°) directional pattern in the planes both parallel and perpendicular to the p–n junction are fabricated. To achieve a low radiation divergence in the p–n junction plane, the active region in this plane was designed in the form of a trapezium. The narrow directional pattern in the plane perpendicular to the p–n junction was ensured by the use of a leaky mode, through which more than 90% of laser power was coupled out. (lasers)

  4. C IV Doppler shifts observed in active region filaments

    NASA Technical Reports Server (NTRS)

    Klimchuk, J. A.

    1986-01-01

    The Doppler shift properties of 21 active region filaments were studied using C IV Dopplergram data. Most are associated with corridors of weak magnetic field that separate opposite polarity strong fields seen in photospheric magnetograms. A majority of the filaments are relatively blue shifted, although several lie very close to the dividing lines between blue and red shift. Only one filament in the samples is clearly red shifted. A new calibration procedure for Dopplergrams indicates that sizable zero point offsets are often required. The center-to-limb behavior of the resulting absolute Doppler shifts suggests that filament flows are usually quite small. It is possible that they vanish.

  5. Acetylcholinesterase Inhibition and Information Processing in the Auditory Cortex

    DTIC Science & Technology

    1986-04-30

    9,24,29,30), or for causing auditory hallucinations (2,23,31,32). Thus, compounds which alter cho- linergic transmission, in particular anticholinesterases...the upper auditory system. Thus, attending to and understanding verbal messages in humans, irrespective of the particular voice which speaks them, may...00, AD ACETYLCHOLINESTERASE INHIBITION AND INFORMATION PROCESSING IN THE AUDITORY CORTEX ANNUAL SUMMARY REPORT DTIC ELECTENORMAN M

  6. Acetylcholinesterase-Based Electrochemical Multiphase Microreactor for Detection of Organophosphorous Compounds (Preprint)

    DTIC Science & Technology

    2007-04-01

    glutaraldehyde. The system was tested with malathion , an organophosphorus pesticide. The detection limit of the sensor in the parts-per-trillion range and...Electric eel acetylcholinesterase (EC 3.1.1.7) and the organophosphate, malathion , were purchased from Aldrich. Electric eel acetylcholinesterase is less...expensive than human acetylcholinesterase and allows us to use a non-toxic organophosphate. Malathion , commonly used as a pesticide, is not

  7. Chromospheric Evolution and the Flare Activity of Super-Active Region NOAA 6555

    NASA Technical Reports Server (NTRS)

    PrasadC, Debi; Ambastha, Ashok; Srivastava, Nandita; Tripathy, Sushanta C.; Hagyard, Mona J.

    1997-01-01

    Super-active region NOAA 6555 was highly flare productive during the period March 21st - 27th, 1991 of its disk passage. We have studied its chromospheric activity using high spatial resolution H alpha filtergrams taken at Udaipur along with MSFC vector magnetograms. A possible relationship of flare productivity and the variation in shear has been explored. Flares were generally seen in those subareas of the active region which possessed closed magnetic field configuration, whereas only minor flares and/or surges occurred in subareas showing open magnetic field configuration. Physical mechanisms responsible for the observed surges are also discussed.

  8. Primary Investigation for the Mechanism of Biatractylolide from Atractylodis Macrocephalae Rhizoma as an Acetylcholinesterase Inhibitor

    PubMed Central

    Xie, Yong-Chao; Ning, Ning; Zhu, Li; Li, Dan-Ning

    2016-01-01

    Biatractylolide was isolated from ethyl acetate extract of dried Atractylodis Macrocephalae Rhizoma root by multistep chromatographic processing. Structure of biatractylolide was confirmed by 1H-NMR and 13C-NMR. The IC50 on acetylcholinesterase (AChE) activity was 6.5458 μg/mL when the control IC50 value of huperzine A was 0.0192 μg/mL. Molecular Docking Software (MOE) was used to discover molecular sites of action between biatractylolide and AChE protein by regular molecular docking approaches. Moreover, biatractylolide downregulated the expression of AChE of MEF and 293T cells in a dose-dependent manner. These results demonstrated that the molecular mechanisms of inhibitory activities of biatractylolide on AChE are not only through binding to AChE, but also via reducing AChE expression by inhibiting the activity of GSK3β. PMID:27642355

  9. THE APPEARANCE OF ACETYLCHOLINESTERASE IN THE MYOTOME OF THE EMBRYONIC RABBIT

    PubMed Central

    Tennyson, Virginia M.; Brzin, Miro; Slotwiner, Paul

    1971-01-01

    Acetylcholinesterase (AChE) activity has been studied in the myoblast of skeletal muscle of the 9–13 day fetal rabbit. Cytochemical activity is present in the nuclear envelope and the endoplasmic reticulum, including its derivatives the subsurface reticulum and the sarcoplasmic reticulum. End product is also found in the Golgi complex of the more differentiated myoblasts. The formation of reticulum-bound acetylcholinesterase in the myoblast appears to be independent of nerve-muscle contact, since the enzyme is present before the outgrowth of the spinal nerve. The nerve lacks cytochemical end product until the myoblast is well differentiated. Possible mechanisms of spontaneous muscle contraction have been discussed. A second type of myotomal cell, which exhibits a poorly localized end product of AChE activity, has been described. The ready solubility of the enzyme or diffusibility of its end product suggests that the enzyme may be a lyoesterase. This cell may be the precursor of the morphologically undifferentiated cell which is closely apposed to the myotubes in later stages of skeletal muscle development. Biochemical studies show a significant increase in AChE activity in the dermomyotome by day 12, when many of the myoblasts are well differentiated and the second type of myotomal cell is prominent. Cytochemical studies have indicated that many of the cells in the sample lack reaction product of enzymic activity, whereas others are very active. Biochemical values, therefore, reflect the amount of enzyme in the dermomyotome as a whole, but give little information on the enzymic content of individual cells. PMID:4256859

  10. The morphology of flare phenomena, magnetic fields, and electric currents in active regions. II - NOAA active region 5747 (1989 October)

    NASA Technical Reports Server (NTRS)

    Leka, K. D.; Canfield, Richard C.; Mcclymont, A. N.; De La Beaujardiere, J.-F.; Fan, Yuhong; Tang, F.

    1993-01-01

    The paper describes October 1989 observations in NOAA Active Region 5747 of the morphology of energetic electron precipitation and high-pressure coronal flare plasmas of three flares and their relation to the vector magnetic field and vertical electric currents. The H-alpha spectroheliograms were coaligned with the vector magnetograms using continuum images of sunspots, enabling positional accuracy of a few arcsec. It was found that, during the gradual phase, the regions of the H-alpha flare that show the effects of enhanced pressure in the overlying corona often encompass extrema of the vertical current density, consistent with earlier work showing a close relationship between H-alpha emission and line-of-sight currents. The data are also consistent with the overall morphology and evolution described by erupting-filament models such as those of Kopp and Pneuman (1976) and Sturrock (1989).

  11. Behaviour of oscillations in loop structures above active regions

    NASA Astrophysics Data System (ADS)

    Kolobov, D. Y.; Kobanov, N. I.; Chelpanov, A. A.; Kochanov, A. A.; Anfinogentov, S. A.; Chupin, S. A.; Myshyakov, I. I.; Tomin, V. E.

    2015-12-01

    In this study we combine the multiwavelength ultraviolet-optical (Solar Dynamics Observatory, SDO) and radio (Nobeyama Radioheliograph, NoRH) observations to get further insight into space-frequency distribution of oscillations at different atmospheric levels of the Sun. We processed the observational data on NOAA 11711 active region and found oscillations propagating from the photospheric level through the transition region upward into the corona. The power maps of low-frequency (1-2 mHz) oscillations reproduce well the fan-like coronal structures visible in the Fe IX 171 Å line. High frequency oscillations (5-7 mHz) propagate along the vertical magnetic field lines and concentrate inside small-scale elements in the umbra and at the umbra-penumbra boundary. We investigated the dependence of the dominant oscillation frequency upon the distance from the sunspot barycentre to estimate inclination of magnetic tubes in higher levels of sunspots where it cannot be measured directly, and found that this angle is close to 40° above the umbra boundaries in the transition region.

  12. Active Region Magnetic Structure Observed in the Photosphere and Chromosphere

    NASA Technical Reports Server (NTRS)

    Leka, K. D.; Metcalf, Thomas R.

    2001-01-01

    The magnetic flux above sunspots and plage in NOAA (National Oceanic and Atmospheric Administration) Active Region 8299 has been measured in the photosphere and the chromosphere. We investigate the vertical magnetic structure above the umbrae, penumbrae and plage regions using quantitative statistical comparisons of the photospheric and chromospheric vector magnetic flux data. The results include: (1) a decrease in flux with height, (2) the direct detection of the superpenumbral canopy in the chromosphere, (3) values for dB/dz which are consistent with earlier investigations when derived from a straight difference between the two datasets but quite low when derived from the delta x B = 0 condition, (4) a monolithic structure in the umbra which extends well into the upper chromosphere with a very complex and varied structure in the penumbra and plage, as evidenced by (5) a uniform magnetic scale height in the umbrae with an abrupt jump to widely varying scale heights in the penumbral and plage regions. Further, we find (6) evidence for a very large (delta z approximately equals 3Mm) height difference between the atmospheric layers sampled in the two magnetograms, almost a factor of three larger than that implied by atmospheric models. We additionally test the apropriateness of using photospheric magnetic flux as a boundary for field-line extrapolations, and find a better agreement with observed coronal structure when the chromospheric flux is used as a boundary.

  13. Photospheric electric current and transition region brightness within an active region

    NASA Technical Reports Server (NTRS)

    Deloach, A. C.; Hagyard, M. J.; Rabin, D.; Moore, R. L.; Smith, B. J., Jr.; West, E. A.; Tandberg-Hanssen, E.

    1984-01-01

    Distributions of vertical electrical current density J(z) calculated from vector measurements of the photospheric magnetic field are compared with ultraviolet spectroheliograms to investigate whether resistive heating is an important source of enhanced emission in the transition region. The photospheric magnetic fields in Active Region 2372 were measured on April 6 and 7, 1980 with the Marshall Space Flight Center vector magnetograph; ultraviolet wavelength spectroheliograms (L-alpha and N V 1239 A) were obtained with the UV Spectrometer and Polarimeter experiment aboard the Solar Maximum Mission satellite. Spatial registration of the J(z) (5 arcsec resolution) and UV (3 arcsec resolution) maps indicates that the maximum current density is cospatial with a minor but persistent UV enhancement, but there is little detected current associated with other nearby bright areas. It is concluded that, although resistive heating may be important in the transition region, the currents responsible for the heating are largely unresolved in the present measurements and have no simple correlation with the residual current measured on 5-arcsec scales.

  14. THE MAGNETIC CLASSIFICATION OF SOLAR ACTIVE REGIONS 1992–2015

    SciTech Connect

    Jaeggli, S. A.; Norton, A. A.

    2016-03-20

    The purpose of this Letter is to address a blindspot in our knowledge of solar active region (AR) statistics. To the best of our knowledge, there are no published results showing the variation of the Mount Wilson magnetic classifications as a function of solar cycle based on modern observations. We show statistics for all ARs reported in the daily Solar Region Summary from 1992 January 1 to 2015 December 31. We find that the α and β class ARs (including all sub-groups, e.g., βγ, βδ) make up fractions of approximately 20% and 80% of the sample, respectively. This fraction is relatively constant during high levels of activity; however, an increase in the α fraction to about 35% and and a decrease in the β fraction to about 65% can be seen near each solar minimum and are statistically significant at the 2σ level. Over 30% of all ARs observed during the years of solar maxima were appended with the classifications γ and/or δ, while these classifications account for only a fraction of a percent during the years near the solar minima. This variation in the AR types indicates that the formation of complex ARs may be due to the pileup of frequent emergence of magnetic flux during solar maximum, rather than the emergence of complex, monolithic flux structures.

  15. Multi-Wavelength Study of Active Region Loop Dynamics

    NASA Astrophysics Data System (ADS)

    Banerjee, D.

    2006-11-01

    Observations have revealed the existence of weak transient disturbances in extended coronal loop systems. These propagating disturbances (PDs) originate from small scale brightenings at the footpoints of the loops and propagate upward along the loops. In all cases observed, the projected propagation speed is close to, but below the expected sound speed in the loops. This suggests that the PDs could be interpreted as slow mode MHD waves. Interpreting the oscillation in terms of different wave modes and/or plasma motions always depend on the line of sight as we observe in the limb or on the center of the disk. The JOP 165 campaign will address some of these questions. MDI and TRACE photospheric and UV imaging of TRACE and SPIRIT have been acquired simultaneously with high temporal and spatial coverage along with the spectroscopic data from CDS. EIT was operated in the shutter-less mode to achieve high Cadence. Some of the off- limb active region dynamics and oscillations observed during this JOP campaign will be focused in this presentation. Plasma condensations and temporal variations in active region loops will be also addressed.

  16. Magnetic field measurements in and above a limb active region

    NASA Astrophysics Data System (ADS)

    Philip, Judge

    2013-07-01

    We analyze spectropolarimetric data of a limb active region (NOAA 11302) obtained on September 22nd 2011 using the Facility Infrared Spectrometer (FIRS) at the Dunn Solar Telescope (DST). Stokes profiles including lines of Si I 1028.7 nm and He I 1083 nm were obtained in three scans over a 45"x75" area. Simultaneous narrow band Ca II K and G-band intensity data were acquired with a cadence of 5s at the DST. The He I data show not only typical active region polarization signatures, but also signatures in plumes -- cool post flare loops -- which extend many Mm into the corona across the visible limb. The plumes have remarkably uniform brightness, and the plume plasma is significantly Doppler shifted as it drains from the corona. Using carefully constructed observing and calibration sequences and applying Principal Component Analysis to remove instrumental artifacts, we achieved a polarization sensitivity approaching 0.02%. With this sensitivity we attempt to diagnose the vector magnetic fields and plasma properties of chromospheric and cool coronal material in and above NOAA 11302. Inversions using various radiative transfer models in the HAZEL code are remarkably consistent with the idea that plume spectra are formed in a simple, slab-like geometry, but that the ``disk'' spectra are formed under more traditional models (Milne-Eddington). The inverted magnetic data of He I lines are compared with photospheric inversions of DST Si I and Fe I data from the Solar Dynamics Observatory.

  17. Material Supply and Magnetic Configuration of an Active Region Filament

    NASA Astrophysics Data System (ADS)

    Zou, P.; Fang, C.; Chen, P. F.; Yang, K.; Hao, Q.; Cao, Wenda

    2016-11-01

    It is important to study the fine structures of solar filaments with high-resolution observations, since it can help us understand the magnetic and thermal structures of the filaments and their dynamics. In this paper, we study a newly formed filament located inside the active region NOAA 11762, which was observed by the 1.6 m New Solar Telescope at Big Bear Solar Observatory from 16:40:19 UT to 17:07:58 UT on 2013 June 5. As revealed by the Hα filtergrams, cool material is seen to be injected into the filament spine with a speed of 5-10 km s-1. At the source of the injection, brightenings are identified in the chromosphere, which are accompanied by magnetic cancellation in the photosphere, implying the importance of magnetic reconnection in replenishing the filament with plasmas from the lower atmosphere. Counter-streamings are detected near one endpoint of the filament, with the plane-of-the-sky speed being 7-9 km s-1 in the Hα red-wing filtergrams and 9-25 km s-1 in the blue-wing filtergrams. The observations are indicative that this active region filament is supported by a sheared arcade without magnetic dips, and the counter-streamings are due to unidirectional flows with alternative directions, rather than due to the longitudinal oscillations of filament threads as in many other filaments.

  18. Photonic crystal lasers using wavelength-scale embedded active region

    NASA Astrophysics Data System (ADS)

    Matsuo, Shinji; Sato, Tomonari; Takeda, Koji; Shinya, Akihiko; Nozaki, Kengo; Kuramochi, Eiichi; Taniyama, Hideaki; Notomi, Masaya; Fujii, Takuro; Hasebe, Koichi; Kakitsuka, Takaaki

    2014-01-01

    Lasers with ultra-low operating energy are desired for use in chip-to-chip and on-chip optical interconnects. If we are to reduce the operating energy, we must reduce the active volume. Therefore, a photonic crystal (PhC) laser with a wavelength-scale cavity has attracted a lot of attention because a PhC provides a large Q-factor with a small volume. To improve this device's performance, we employ an embedded active region structure in which the wavelength-scale active region is buried with an InP PhC slab. This structure enables us to achieve effective confinement of both carriers and photons, and to improve the thermal resistance of the device. Thus, we have obtained a large external differential quantum efficiency of 55% and an output power of -10 dBm by optical pumping. For electrical pumping, we use a lateral p-i-n structure that employs Zn diffusion and Si ion implantation for p-type and n-type doping, respectively. We have achieved room-temperature continuous-wave operation with a threshold current of 7.8 µA and a maximum 3 dB bandwidth of 16.2 GHz. The results of an experimental bit error rate measurement with a 10 Gbit s-1 NRZ signal reveal the minimum operating energy for transferring a single bit of 5.5 fJ. These results show the potential of this laser to be used for very short reach interconnects. We also describe the optimal design of cavity quality (Q) factor in terms of achieving a large output power with a low operating energy using a calculation based on rate equations. When we assume an internal absorption loss of 20 cm-1, the optimized coupling Q-factor is 2000.

  19. Two heparin-binding domains are present on the collagenic tail of asymmetric acetylcholinesterase.

    PubMed

    Deprez, P N; Inestrosa, N C

    1995-05-12

    The collagen-tailed form of acetylcholinesterase (AChE) binds to heparin and heparan sulfate proteoglycans. We have employed synthetic peptides corresponding to the central collagenic region of the tail of AChE, to identify the heparin-binding domains of the tail of asymmetric AChE. Two putative heparin-binding consensus sequences were localized in the collagenic tail. Peptides containing such sequences (P-(145-159) and P-(249-262)) were able to release asymmetric AChE bound to heparin-agarose. A triple mutation, Asn-Asp-Gly-Gly instead of Arg-His-Gly-Arg, completely abolishes the capacity of the peptide P-(145-159) to elute AChE from the heparin column. Our results suggest that the interaction between the collagen-tailed AChE and proteoglycans is mediated by clusters of basic residues that form two belts around the triple helix of the collagenic tail.

  20. Nantenine as an acetylcholinesterase inhibitor: SAR, enzyme kinetics and molecular modeling investigations

    PubMed Central

    Pecic, Stevan; McAnuff, Marie A.; Harding, Wayne W.

    2015-01-01

    Nantenine, as well as a number of flexible analogs, were evaluated for acetylcholinesterase (AChE) inhibitory activity in microplate spectrophotometric assays based on Ellman’s method. It was found that the rigid aporphine core of nantenine is an important structural requirement for its anticholinesterase activity. Nantenine showed mixed inhibition kinetics in enzyme assays. Molecular docking experiments suggest that nantenine binds preferentially to the catalytic site of AChE but is also capable of interacting with the peripheral anionic site (PAS) of the enzyme, thus accounting for its mixed inhibition profile. The aporphine core of nantenine may thus be a useful template for the design of novel PAS or dual-site AChE inhibitors. Inhibiting the PAS is desirable for prevention of aggregation of the amyloid peptide Aβ, a major causative factor in the progression of Alzheimer’s disease (AD). PMID:20583856

  1. Selective inhibition of human acetylcholinesterase by xanthine derivatives: in vitro inhibition and molecular modeling investigations.

    PubMed

    Mohamed, Tarek; Osman, Wesseem; Tin, Gary; Rao, Praveen P N

    2013-08-01

    The commonly used beverage and psychostimulant caffeine is known to inhibit human acetylcholinesterase enzyme. This pharmacological activity of caffeine is partly responsible for its cognition enhancing properties. However, the exact mechanisms of its binding to human cholinesterases (acetyl and butyrylcholinesterase; hAChE and hBuChE) are not well known. In this study, we investigated the cholinesterase inhibition by the xanthine derivatives caffeine, pentoxifylline, and propentofylline. Among them, propentofylline was the most potent AChE inhibitor (hAChE IC₅₀=6.40 μM). The hAChE inhibitory potency was of the order: caffeine (hAChE IC₅₀=7.25 μM)50 μM) relative to the reference agent donepezil (hBuChE IC₅₀=13.60 μM). Molecular modeling investigations indicate that caffeine binds primarily in the catalytic site (Ser203, Glu334 and His447) region of hAChE whereas pentoxifylline and propentofylline are able to bind to both the catalytic site and peripheral anionic site due to their increased bulk/size, thereby exhibiting superior AChE inhibition relative to caffeine. In contrast, their lack of hBuChE inhibition is due to a larger binding site and lack of key aromatic amino acids. In summary, our study has important implications in the development of novel caffeine derivatives as selective AChE inhibitors with potential application as cognitive enhancers and to treat various forms of dementia.

  2. Regional variation in myofilament length-dependent activation.

    PubMed

    Cazorla, Olivier; Lacampagne, Alain

    2011-07-01

    The Frank-Starling law is an important regulatory mechanism of the heart that links the end-diastolic volume with the systolic ejection fraction. This beat-to-beat regulation of the heart, underlined at the cellular level by higher myofilament calcium sensitivity at longer sarcomere length, is known as length-dependent activation or stretch sensitization of activation. However, the heart is structurally and functionally heterogeneous and asymmetrical. Specifically, contractile properties are not uniform within the left ventricle partly due to transmural differences in action potential waveforms and calcium homeostasis. The present review will focus on the role of the contractile machinery in the transmural contractile heterogeneity and its adaptation to changes in muscle strain. The expression of different myosin isoforms, the level of titin-based passive tension, and thin and thick sarcomeric regulatory proteins are considered to explain the regional cellular contractile properties. Finally, the importance of transmural heterogeneity of length-dependent activation and the consequences of its modification on the heart mechanics are discussed. Despite extensive research since the characterization of the Frank-Starling law, the molecular mechanisms by which strain information is transduced to the contractile machinery have not been fully determined yet.

  3. Repetitive Transcranial Magnetic Stimulation Activates Specific Regions in Rat Brain

    NASA Astrophysics Data System (ADS)

    Ji, Ru-Rong; Schlaepfer, Thomas E.; Aizenman, Carlos D.; Epstein, Charles M.; Qiu, Dike; Huang, Justin C.; Rupp, Fabio

    1998-12-01

    Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive technique to induce electric currents in the brain. Although rTMS is being evaluated as a possible alternative to electroconvulsive therapy for the treatment of refractory depression, little is known about the pattern of activation induced in the brain by rTMS. We have compared immediate early gene expression in rat brain after rTMS and electroconvulsive stimulation, a well-established animal model for electroconvulsive therapy. Our result shows that rTMS applied in conditions effective in animal models of depression induces different patterns of immediate-early gene expression than does electroconvulsive stimulation. In particular, rTMS evokes strong neural responses in the paraventricular nucleus of the thalamus (PVT) and in other regions involved in the regulation of circadian rhythms. The response in PVT is independent of the orientation of the stimulation probe relative to the head. Part of this response is likely because of direct activation, as repetitive magnetic stimulation also activates PVT neurons in brain slices.

  4. In-depth survey of sunspot and active region catalogs

    NASA Astrophysics Data System (ADS)

    Lefèvre, Laure; Clette, Frédéric; Baranyi, Tunde

    2011-08-01

    When consulting detailed photospheric catalogs for solar activity studies spanning long time intervals, solar physicists face multiple limitations in the existing catalogs: finite or fragmented time coverage, limited time overlap between catalogs and even more importantly, a mismatch in contents and conventions. In view of a study of new sunspot-based activity indices, we have conducted a comprehensive survey of existing catalogs. In a first approach, we illustrate how the information from parallel catalogs can be merged to form a much more comprehensive record of sunspot groups. For this, we use the unique Debrecen Photoheliographic Data (DPD), which is already a composite of several ground observatories and SOHO data, and the USAF/Mount Wilson catalog from the Solar Optical Observing Network (SOON). We also describe our semi-interactive cross-identification method, which was needed to match the non-overlapping solar active region nomenclature, the most critical and subtle step when working with multiple catalogs. This effort, focused here first on the last two solar cycles, should lead to a better central database collecting all available sunspot group parameters to address future solar cycle studies beyond the traditional sunspot index time series Ri.

  5. High yield production of a mutant Nippostrongylus brasiliensis acetylcholinesterase in Pichia pastoris and its purification.

    PubMed

    Richter, Sven; Nieveler, Jens; Schulze, Holger; Bachmann, Till T; Schmid, Rolf D

    2006-04-05

    The mutant M301A of the acetylcholinesterase B from Nippostrongylus brasiliensis (NbAChE) was produced in a high-cell-density fermentation of a recombinant methylotrophic yeast Pichia pastoris. Dissolved oxygen (DO) spikes were used as an indicator for feeding the carbon source. Wet cell weight (WCW) reached after 8 days a maximum value of 316 g/L and the OD600 at this time was 280. The acetylcholinesterase activity increased up to 6,600 U/mL corresponding to an expression rate of 2 g of NbAChE per liter supernatant. The specific activity of the mutant NbAChE was determined after purification as 3,300 U/mg. Active site titration with chlorpyrifos, a strong AChE inhibitor, yielded in a specific activity of 3,400 U/mg. The enzyme was secreted by Pichia pastoris. Therefore, it could be concentrated from culture broth by cross-flow-filtration (50 kDa cut-off membrane). It was further purified in one-step anion-exchange chromatography, using a XK 50/20 column filled with 125 mL Q Sepharose HP. Mutant NbAChE was purified 1.9-fold up to a purity of 97% and a yield of 87%. The isolated enzyme was nearly homogenous, as seen on the silver stained SDS-PAGE as well as by a single peak after gel filtration. This extraordinary high expression rate and the ease of purification is an important prerequisite for their practical application, for example in biosensors for the detection of neurotoxic insecticides.

  6. Demarcations of the mechanosensory projection zones in the raccoon thalamus, shown by cytochrome oxidase, acetylcholinesterase, and Nissl stains.

    PubMed

    Wiener, S I; Johnson, J I; Ostapoff, E M

    1987-04-22

    To determine anatomically the boundaries and internal organization of the kinesthetic and cutaneous mechanosensory regions of the ventrobasal thalamus, alternate section series from electrophysiologically mapped tissues from 14 raccoons were stained for cytochrome oxidase, myelinated fibers, acetylcholinesterase, and Nissl substance. Microelectrode tracks, along with electrolytic lesions placed as tissue markers, reveal that the mechanoreceptor projection zones have higher cytochrome oxidase and lower acetylcholinesterase staining than some neighboring regions. Both these enzymatic stains reveal particularly sharp boundaries separating the mechanoresponsive region, from the lateral posterior nucleus dorsally and from the ventroposterior inferior nucleus ventrally. The kinesthetic projection zone is often separated from other mechanoreceptor projections by bundles as well as laminae of myelinated fibers, similar to those separating cutaneous projections from distinct body parts. These subdivisions are particularly well marked by the cytochrome oxidase stain. The combination, in neighboring sections, of the use of the several stains adds considerably to the visible delineation of these functionally distinct regions, beyond what can be seen in Nissl-stained sections.

  7. On the modified active region design of interband cascade lasers

    SciTech Connect

    Motyka, M.; Ryczko, K.; Dyksik, M.; Sęk, G.; Misiewicz, J.; Weih, R.; Dallner, M.; Kamp, M.; Höfling, S.

    2015-02-28

    Type II InAs/GaInSb quantum wells (QWs) grown on GaSb or InAs substrates and designed to be integrated in the active region of interband cascade lasers (ICLs) emitting in the mid infrared have been investigated. Optical spectroscopy, combined with band structure calculations, has been used to probe their electronic properties. A design with multiple InAs QWs has been compared with the more common double W-shaped QW and it has been demonstrated that it allows red shifting the emission wavelength and enhancing the transition oscillator strength. This can be beneficial for the improvements of the ICLs performances, especially when considering their long-wavelength operation.

  8. Chromospheric magnetic fields of an active region filament

    NASA Astrophysics Data System (ADS)

    Xu, Z.; Solanki, S.; Lagg, A.

    2012-06-01

    Vector magnetic fields of an active region filament are co-spatially and co-temporally mapped in photosphere and upper chromosphere, by using spectro-polarimetric observations made by Tenerife Infrared Polarimeter (TIP II) at the German Vacuum Tower Telescope (VTT). A Zeeman-based ME inversion is performed on the full Stokes vectors of both the photospheric Si I 1082.7 nm and the chromospheric He I 1083.0 nm lines. We found that the strong magnetic fields, with the field strength of 600 - 800 G in the He I line formation height, are not uncommon among AR filaments. But such strong magnetic field is not always found in AR filaments.

  9. SIGN SINGULARITY AND FLARES IN SOLAR ACTIVE REGION NOAA 11158

    SciTech Connect

    Sorriso-Valvo, L.; De Vita, G.; Kazachenko, M. D.; Krucker, S.; Welsch, B. T.; Fisher, G. H.; Primavera, L.; Servidio, S.; Lepreti, F.; Carbone, V.; Vecchio, A.

    2015-03-01

    Solar Active Region NOAA 11158 has hosted a number of strong flares, including one X2.2 event. The complexity of current density and current helicity are studied through cancellation analysis of their sign-singular measure, which features power-law scaling. Spectral analysis is also performed, revealing the presence of two separate scaling ranges with different spectral index. The time evolution of parameters is discussed. Sudden changes of the cancellation exponents at the time of large flares and the presence of correlation with Extreme-Ultra-Violet and X-ray flux suggest that eruption of large flares can be linked to the small-scale properties of the current structures.

  10. Focused ultrasound modulates region-specific brain activity

    PubMed Central

    Yoo, Seung-Schik; Bystritsky, Alexander; Lee, Jong-Hwan; Zhang, Yongzhi; Fischer, Krisztina; Min, Byoung-Kyong; McDannold, Nathan J.; Pascual-Leone, Alvaro; Jolesz, Ferenc A.

    2012-01-01

    We demonstrated the in vivo feasibility of using focused ultrasound (FUS) to transiently modulate (through either stimulation or suppression) the function of regional brain tissue in rabbits. FUS was delivered in a train of pulses at low acoustic energy, far below the cavitation threshold, to the animal's somatomotor and visual areas, as guided by anatomical and functional information from magnetic resonance imaging (MRI). The temporary alterations in the brain function affected by the sonication were characterized by both electrophysiological recordings and functional brain mapping achieved through the use of functional MRI (fMRI). The modulatory effects were bimodal, whereby the brain activity could either be stimulated or selectively suppressed. Histological analysis of the excised brain tissue after the sonication demonstrated that the FUS did not elicit any tissue damages. Unlike transcranial magnetic stimulation, FUS can be applied to deep structures in the brain with greater spatial precision. Transient modulation of brain function using image-guided and anatomically-targeted FUS would enable the investigation of functional connectivity between brain regions and will eventually lead to a better understanding of localized brain functions. It is anticipated that the use of this technology will have an impact on brain research and may offer novel therapeutic interventions in various neurological conditions and psychiatric disorders. PMID:21354315

  11. Slow Magnetosonic Waves and Fast Flows in Active Region Loops

    NASA Technical Reports Server (NTRS)

    Ofman, L.; Wang, T. J.; Davila, J. M.

    2012-01-01

    Recent extreme ultraviolet spectroscopic observations indicate that slow magnetosonic waves are present in active region (AR) loops. Some of the spectral data were also interpreted as evidence of fast (approx 100-300 km/s) quasiperiodic flows. We have performed three-dimensional magnetohydrodynamic (3D MHD) modeling of a bipolar AR that contains impulsively generated waves and flows in coronal loops. The model AR is initiated with a dipole magnetic field and gravitationally stratified density, with an upflow-driven steadily or periodically in localized regions at the footpoints of magnetic loops. The resulting flows along the magnetic field lines of the AR produce higher density loops compared to the surrounding plasma by injection of material into the flux tubes and the establishment of siphon flow.We find that the impulsive onset of flows with subsonic speeds result in the excitation of damped slow magnetosonic waves that propagate along the loops and coupled nonlinearly driven fast-mode waves. The phase speed of the slow magnetosonic waves is close to the coronal sound speed. When the amplitude of the driving pulses is increased we find that slow shock-like wave trains are produced. When the upflows are driven periodically, undamped oscillations are produced with periods determined by the periodicity of the upflows. Based on the results of the 3D MHD model we suggest that the observed slow magnetosonic waves and persistent upflows may be produced by the same impulsive events at the bases of ARs.

  12. The transcriptionally active regions in the genome of Bacillus subtilis

    PubMed Central

    Rasmussen, Simon; Nielsen, Henrik Bjørn; Jarmer, Hanne

    2009-01-01

    The majority of all genes have so far been identified and annotated systematically through in silico gene finding. Here we report the finding of 3662 strand-specific transcriptionally active regions (TARs) in the genome of Bacillus subtilis by the use of tiling arrays. We have measured the genome-wide expression during mid-exponential growth on rich (LB) and minimal (M9) medium. The identified TARs account for 77.3% of the genes as they are currently annotated and additionally we find 84 putative non-coding RNAs (ncRNAs) and 127 antisense transcripts. One ncRNA, ncr22, is predicted to act as a translational control on cstA and an antisense transcript was observed opposite the housekeeping sigma factor sigA. Through this work we have discovered a long conserved 3′ untranslated region (UTR) in a group of membrane-associated genes that is predicted to fold into a large and highly stable secondary structure. One of the genes having this tail is efeN, which encodes a target of the twin-arginine translocase (Tat) protein translocation system. PMID:19682248

  13. Comparison of Solar Active Region Complexity Andgeomagnetic Activity from 1996 TO 2014

    NASA Astrophysics Data System (ADS)

    Tanskanen, E. I.; Nikbakhsh, S.; Perez-Suarez, D.; Hackman, T.

    2015-12-01

    We have studied the influence of magnetic complexity of solar Active Regions (ARs)on geomagnetic activity from 1996 to 2014. Sunspots are visual indicators of ARswhere the solar magnetic field is disturbed. We have used International, American,Space Environment Service Center (SESC) and Space Weather Prediction Center(SWPC) sunspot numbers to examine ARs. Major manifestations of solar magneticactivity, such as flares and Coronal Mass Ejections (CMEs), are associated withARs. For this study we chose the Mount Wilson scheme. It classifies ARs in terms oftheir magnetic topology from the least complex (?) to the most complex one ( ?).Several cases have been found where the more complex structures produce strongerflares and CMEs than the less complex ones. We have a list of identified substormsavailable with different phases and their durations. This will be compared to ourmagnetic complexity data to analyse the effects of active region magnetic complexityto the magnetic activity on the vicinity of the Earth.

  14. Measurement of p-nitrophenyl acetate esterase activity (EA), total antioxidant capacity (TAC), total oxidant status (TOS) and acetylcholinesterase (AChE) in gills and digestive gland of Mytilus galloprovincialis exposed to binary mixtures of Pb, Cd and Cu.

    PubMed

    Franco-Martinez, Lorena; Romero, Diego; García-Navarro, José A; Tecles, Fernando; Teles, Mariana; Tvarijonaviciute, Asta

    2016-12-01

    The aims of the present work were (1) to evaluate oxidative stress biomarkers and AChE in two tissues of wild mussel (Mytilus galloprovincialis) of high biochemical activity and accumulation capacity (gills and digestive gland) and (2) to study the behaviour of these biomarkers in presence of heavy metals. For this, EA, TOS, TAC and AChE were measured in tissues of mussels exposed to binary combination of Pb, Cd and Cu. Mussels (n = 36) were exposed to one of the binary mixtures of Pb (1000 μg L(-1)), Cd (100 μg L(-1)) and Cu (100 μg L(-1)) for 7 days, under controlled conditions. Gills and digestive gland were extracted and frozen at -80 °C until analysis. The automatic methods employed for the measurement of EA, TAC, TOS and AChE in M. galloprovincialis revealed higher levels of these biomarkers in digestive gland than gills. Study results suggest that gills would be the tissue of election for study oxidative stress markers, whereas digestive tissue should be selected for AChE measurements in case of evaluation of combined metal toxicity in mussels.

  15. Cloud condensation nuclei activity and droplet activation kinetics of wet processed regional dust samples and minerals

    NASA Astrophysics Data System (ADS)

    Kumar, P.; Sokolik, I. N.; Nenes, A.

    2011-08-01

    This study reports laboratory measurements of particle size distributions, cloud condensation nuclei (CCN) activity, and droplet activation kinetics of wet generated aerosols from clays, calcite, quartz, and desert soil samples from Northern Africa, East Asia/China, and Northern America. The dependence of critical supersaturation, sc, on particle dry diameter, Ddry, is used to characterize particle-water interactions and assess the ability of Frenkel-Halsey-Hill adsorption activation theory (FHH-AT) and Köhler theory (KT) to describe the CCN activity of the considered samples. Wet generated regional dust samples produce unimodal size distributions with particle sizes as small as 40 nm, CCN activation consistent with KT, and exhibit hygroscopicity similar to inorganic salts. Wet generated clays and minerals produce a bimodal size distribution; the CCN activity of the smaller mode is consistent with KT, while the larger mode is less hydrophilic, follows activation by FHH-AT, and displays almost identical CCN activity to dry generated dust. Ion Chromatography (IC) analysis performed on regional dust samples indicates a soluble fraction that cannot explain the CCN activity of dry or wet generated dust. A mass balance and hygroscopicity closure suggests that the small amount of ions (from low solubility compounds like calcite) present in the dry dust dissolve in the aqueous suspension during the wet generation process and give rise to the observed small hygroscopic mode. Overall these results identify an artifact that may question the atmospheric relevance of dust CCN activity studies using the wet generation method. Based on the method of threshold droplet growth analysis, wet generated mineral aerosols display similar activation kinetics compared to ammonium sulfate calibration aerosol. Finally, a unified CCN activity framework that accounts for concurrent effects of solute and adsorption is developed to describe the CCN activity of aged or hygroscopic dusts.

  16. Antioxidant and acetylcholinesterase-inhibitory properties of long-term stored medicinal plants

    PubMed Central

    2012-01-01

    Background Medicinal plants are possible sources for future novel antioxidant compounds in food and pharmaceutical formulations. Recent attention on medicinal plants emanates from their long historical utilisation in folk medicine as well as their prophylactic properties. However, there is a dearth of scientific data on the efficacy and stability of the bioactive chemical constituents in medicinal plants after prolonged storage. This is a frequent problem in African Traditional Medicine. Methods The phytochemical, antioxidant and acetylcholinesterase-inhibitory properties of 21 medicinal plants were evaluated after long-term storage of 12 or 16 years using standard in vitro methods in comparison to freshly harvested materials. Results The total phenolic content of Artemisia afra, Clausena anisata, Cussonia spicata, Leonotis intermedia and Spirostachys africana were significantly higher in stored compared to fresh materials. The flavonoid content were also significantly higher in stored A. afra, C. anisata, C. spicata, L. intermedia, Olea europea and Tetradenia riparia materials. With the exception of Ekebergia capensis and L. intermedia, there were no significant differences between the antioxidant activities of stored and fresh plant materials as measured in the β-carotene-linoleic acid model system. Similarly, the EC50 values based on the 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging assay were generally lower for stored than fresh material. Percentage inhibition of acetylcholinesterase was generally similar for both stored and fresh plant material. Stored plant material of Tetradenia riparia and Trichilia dregeana exhibited significantly higher AChE inhibition than the fresh material. Conclusions The current study presents evidence that medicinal plants can retain their biological activity after prolonged storage under dark conditions at room temperature. The high antioxidant activities of stable bioactive compounds in these medicinal plants

  17. Long-Period ULF Wave Activity in the Cusp Region

    NASA Astrophysics Data System (ADS)

    Pilipenko, V.; Belakhovsky, V.; Engebretson, M. J.; Kozlovsky, A.

    2013-12-01

    We compare simultaneous observations of long-period ULF wave activity from the Svalbard/IMAGE and Greenland fluxgate magnetometer profiles covering the expected cusp geomagnetic latitudes. Irregular Pulsations at Cusp Latitudes (IPCL) and narrow-band Pc5 waves are found to be a ubiquitous element of ULF activity in the dayside high-latitude region. To identify the ionospheric projections of the cusp, we use the width of the return signal of the SuperDARN radar covering the Svalbard archipelago, predictions of empirical cusp models, and augmented whenever possible by DMSP identification of magnetospheric boundary domains. The meridional spatial structure of IPCL/Pc5 pulsation spectral power has been found to have a localized latitudinal peak, but not under the cusp proper as was previously thought, but several degrees southward from the equatorward cusp boundary. Possible mechanisms and their relevance to observational data are discussed. The occurrence of IPCL and Pc5 waves in the dayside boundary layers is a challenge to modelers, because so far their mechanism has not been firmly identified.

  18. E region electric field dependence of the solar activity

    NASA Astrophysics Data System (ADS)

    Denardini, C. M.; Moro, J.; Resende, L. C. A.; Chen, S. S.; Schuch, N. J.; Costa, J. E. R.

    2015-10-01

    We have being studying the zonal and vertical E region electric field components inferred from the Doppler shifts of type 2 echoes (gradient drift irregularities) detected with the 50 MHz backscatter coherent radar set at São Luis, Brazil (SLZ, 2.3°S, 44.2°W) during the solar cycle 24. In this report we present the dependence of the vertical and zonal components of this electric field with the solar activity, based on the solar flux F10.7. For this study we consider the geomagnetically quiet days only (Kp ≤ 3+). A magnetic field-aligned-integrated conductivity model was developed for proving the conductivities, using the IRI-2007, the MISIS-2000, and the IGRF-11 models as input parameters for ionosphere, neutral atmosphere, and Earth magnetic field, respectively. The ion-neutron collision frequencies of all the species are combined through the momentum transfer collision frequency equation. The mean zonal component of the electric field, which normally ranged from 0.19 to 0.35 mV/m between the 8 and 18 h (LT) in the Brazilian sector, show a small dependency with the solar activity. Whereas the mean vertical component of the electric field, which normally ranges from 4.65 to 10.12 mV/m, highlights the more pronounced dependency of the solar flux.

  19. Surface display and bioactivity of Bombyx mori acetylcholinesterase on Pichia pastoris

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To construct the Pichia pastoris (P. pastoris) cell surface display system of Bombyx mori acetylcholinesterase (BmAChE), the gene for the anchor protein (AGa1) was obtained from Saccharomyces cerevisiae and was fused with the modified Bombyx mori acetylcholinesterase gene (bmace) and transformed int...

  20. Mechanism-Based Analysis of Acetylcholinesterase Inhibitory Potency of Organophosphates, Carbamates, and Their Analogs

    EPA Science Inventory

    Acetylcholinesterase (AChE) is a key enzyme in the nervous system of animals, terminating impulse transmission by rapid hydrolysis of the neurotransmitter acetylcholine. Organophosphate (OP) and carbamate esters can inhibit acetylcholinesterase (AChE) by binding covalently to a s...

  1. Electrophysiological and Ultrastructural Characterization of Neuromuscular Junctions in Diaphragm Muscle of Acetylcholinesterase Knockout Mice

    DTIC Science & Technology

    2008-04-01

    Electrophysiological and Ultrastructural Characterization of Neuromuscular Junctions in 5a. CONTRACT NUMBER Diaphragm Muscle of Acetylcholinesterase Knockout Mice...AChE +/+) and acetylcholinesterase knockout (AChE -/-) mice to determine the compensatory mechanism manifested by the neuromuscular junction to...had smaller nerve terminals and diminished pre- and postsynaptic surface contacts relative to neuromuscular junctions of AChE +/+ mice. The

  2. The morphology of flare phenomena, magnetic fields, and electric currents in active regions. III - NOAA active region 6233 (1990 August)

    NASA Technical Reports Server (NTRS)

    De La Beaujardiere, J.-F.; Canfield, Richard C.; Leka, K. D.

    1993-01-01

    We investigate the spatial relationship between vertical electric currents and flare phenomena in NOAA Active Region 6233, which was observed 1990, August 28-31 at Mees Solar Observatory. The two flares studied are the 1N/M1.8 flare on August 28, 22:30 UT and the 1N/M1.6 flare on August 29, 20:35 UT. Using Stokes polarimetry we make magnetograms of the region and compute the vertical current density. Using H-alpha imaging spectroscopy we identify sites of intense nonthermal electron precipitation or of high coronal pressure. The precipitation in these flares is barely strong enough to be detectable. We find that both precipitation and high pressure tend to occur near vertical currents, but that neither phenomenon is cospatial with current maxima. In contrast with the conclusion of other authors, we argue that these observations do not support a current-interruption model for flares, unless the relevant currents are primarily horizontal. The magnetic morphology and temporal evolution of these flares suggest that an erupting filament model may be relevant, but this model does not explicitly predict the relationship between precipitation, high pressure, and vertical currents.

  3. Virtual screening discovery of new acetylcholinesterase inhibitors issued from CERMN chemical library.

    PubMed

    Sopkova-de Oliveira Santos, Jana; Lesnard, Aurelien; Agondanou, Jean-Hugues; Dupont, Nathalie; Godard, Anne-Marie; Stiebing, Silvia; Rochais, Christophe; Fabis, Frederic; Dallemagne, Patrick; Bureau, Ronan; Rault, Sylvain

    2010-03-22

    In our quest to find new inhibitors able to inhibit acetylcholinesterase (AChE) and, at the same time, to protect neurons from beta amyloid toxicity, i.e., inhibitors interacting with the catalytic anionic subsite as well as with the peripherical anionic site of AChE, a virtual screening of the Centre d'Etudes et de Recherche sur le Medicament de Normandie (CERMN) chemical library was carried out. Two complementary approaches were applied, i.e., a ligand- and a structure-based screening. Each screening led to the selection of different compounds, but only two were present in both screening results. In vitro tests on AChE showed that one of those compounds presented a very good inhibition activity, of the same order as Donepezil. This result shows the real complementary of both methods for the discovery of new ligands.

  4. Acetylcholinesterase-reduced graphene oxide hybrid films for organophosphorus neurotoxin sensing via quartz crystal microbalance

    NASA Astrophysics Data System (ADS)

    Tang, Shi; Ma, Wenying; Xie, Guangzhong; Su, Yuanjie; Jiang, Yadong

    2016-09-01

    An acetylcholinesterase (AChE)-reduced graphene oxide (RGO) hybrid films based biosensor enabled by quartz crystal microbalance (QCM) has been developed for the detection of organophosphorus neurotoxin in gas phase at room temperature. To improve the sensing performance, RGO was used to immobilize large quantities of enzyme and provide a favorable microenvironment to maintain the enzyme activity. The experimental results reveal that the response of AChE-RGO/glutaraldehyde based sensors is about 8 times larger than that of the AChE with the sensitivity of 1.583 Hz/mg/m3. 1.0 mg amount of RGO, 5% concentration of glutaraldehyde and pH 6.8 is the optimal condition of this biosensor.

  5. Graphene quantum dots for ultrasensitive detection of acetylcholinesterase and its inhibitors

    NASA Astrophysics Data System (ADS)

    Li, Nan; Wang, Xuewan; Chen, Jie; Sun, Lei; Chen, Peng

    2015-09-01

    Graphene quantum dots (GQDs) are emerging zero-dimensional materials promising a wide spectrum of novel applications including development of optical sensors. Herein, a GQD-based fluorometric sensor is devised to detect acetylcholinesterase (AChE, a critical enzyme in central nervous system and neuromuscular junctions) with an ultralow detection limit (0.58 pM with S/N of 5.0), using a photoluminescence ‘turn-off’ mechanism. This simple ‘mix-and-detect’ platform can also be employed to sense a variety of compounds that can directly or indirectly inhibit the enzymatic activities of AChE, such as nerve gases, pesticides, and therapeutic drugs. As the proof-of-concept demonstrations, we show the sensitive detection of paraoxon (a pesticide), tacrine (a drug to treat Alzheimer’s disease), and dopamine (an important neurotransmitter).

  6. Purification and characterization of acetylcholinesterase from desert cobra (Walterinnesia aegyptia) venom.

    PubMed

    Duhaiman, A S; Alhomida, A S; Rabbani, N; Kamal, M A; al-Jafari, A A

    1996-01-01

    Acetylcholinesterase (AChE) has been identified and purified from the venom of desert cobra (W aegyptia) to apparent homogeneity using a TSK G 3000 SW gel filtration column and a Mono Q anion-exchange column. AChE was purified to homogeneity as established by sodium dodecylsulfate/polyacrylamide gel electrophoresis. The specific activity of AChE was 357 IU/mg with acetylthiocholine iodide as substrate. The denatured W aegyptia venom AChE displayed a molecular mass of 67000 +/- 3000 Da suggesting it was a single polypeptide. Isoelectric focusing of AChE revealed that the enzyme exists in different isoforms, with isoelectric points ranging between pH 7.4-7.9. The kinetic parameters (Km and Vmax) and IC50 of AChE inhibition by procaine, tetracaine and physostigmine were investigated in the present study.

  7. Ethynylphenyl carbonates and carbamates as dual-action acetylcholinesterase inhibitors and anti-inflammatory agents.

    PubMed

    Saxena, Jaya; Meloni, David; Huang, Mou-Tuan; Heck, Diane E; Laskin, Jeffrey D; Heindel, Ned D; Young, Sherri C

    2015-12-01

    Novel ethynylphenyl carbonates and carbamates containing carbon- and silicon-based choline mimics were synthesized from their respective phenol and aniline precursors and screened for anticholinesterase and anti-inflammatory activities. All molecules were micromolar inhibitors of acetylcholinesterase (AChE), with IC50s of 28-86 μM; the carbamates were two-fold more potent than the carbonates. Two of the most potent AChE inhibitors suppressed 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation by 40%. Furthermore, these molecules have physicochemical properties in the range of other CNS drugs. These molecules have the potential to treat inflammation; they could also dually target Alzheimer's disease through restoration of cholinergic balance and inflammation suppression.

  8. ON MAGNETIC ACTIVITY BAND OVERLAP, INTERACTION, AND THE FORMATION OF COMPLEX SOLAR ACTIVE REGIONS

    SciTech Connect

    McIntosh, Scott W.; Leamon, Robert J.

    2014-11-20

    Recent work has revealed a phenomenological picture of the how the ∼11 yr sunspot cycle of the Sun arises. The production and destruction of sunspots is a consequence of the latitudinal-temporal overlap and interaction of the toroidal magnetic flux systems that belong to the 22 yr magnetic activity cycle and are rooted deep in the Sun's convective interior. We present a conceptually simple extension of this work, presenting a hypothesis on how complex active regions can form as a direct consequence of the intra- and extra-hemispheric interaction taking place in the solar interior. Furthermore, during specific portions of the sunspot cycle, we anticipate that those complex active regions may be particularly susceptible to profoundly catastrophic breakdown, producing flares and coronal mass ejections of the most severe magnitude.

  9. Contribution of regional brain melanocortin receptor subtypes to elevated activity energy expenditure in lean, active rats

    PubMed Central

    Shukla, Charu; Koch, Lauren G.; Britton, Steven L.; Cai, Minying; Hruby, Victor J.; Bednarek, Maria; Novak, Colleen M.

    2015-01-01

    Physical activity and non-exercise activity thermogenesis (NEAT) are crucial factors accounting for individual differences in body weight, interacting with genetic predisposition. In the brain, a number of neuroendocrine intermediates regulate food intake and energy expenditure (EE); this includes the brain melanocortin (MC) system, consisting of melanocortin peptides as well as their receptors (MCR). MC3R and MC4R have emerged as critical modulators of EE and food intake. To determine how variance in MC signaling may underlie individual differences in physical activity levels, we examined behavioral response to MC receptor agonists and antagonists in rats that show high and low levels of physical activity and NEAT, that is, high- and low-capacity runners (HCR, LCR), developed by artificial selection for differential intrinsic aerobic running capacity. Focusing on the hypothalamus, we identified brain region-specific elevations in expression of MCR 3, 4, and also MC5R, in the highly active, lean HCR relative to the less active and obesity-prone LCR. Further, the differences in activity and associated EE as a result of MCR activation or suppression using specific agonists and antagonists were similarly region-specific and directly corresponded to the differential MCR expression patterns. The agonists and antagonists investigated here did not significantly impact food intake at the doses used, suggesting that the differential pattern of receptor expression may by more meaningful to physical activity than to other aspects of energy balance regulation. Thus, MCR-mediated physical activity may be a key neural mechanism in distinguishing the lean phenotype and a target for enhancing physical activity and NEAT. PMID:26404873

  10. Potent acetylcholinesterase inhibitory compounds from Myristica fragrans.

    PubMed

    Cuong, To Dao; Hung, Tran Manh; Han, Hyoung Yun; Roh, Hang Sik; Seok, Ji-Hyeon; Lee, Jong Kwon; Jeong, Ja Young; Choi, Jae Sue; Kim, Jeong Ah; Min, Byung Sun

    2014-04-01

    The anti-cholinesterase activity was evaluated of the ethyl acetate fraction of the methanol extract of Myristica fragrans Houtt (Myristicaceae) seeds and of compounds isolated from it by various chromatographic techniques. The chemical structures of the compounds were determined from spectroscopic analyses (NMR data). Thirteen compounds (1-13) were isolated and identified. Compound 8 { [(7S)-8'-(4'-hydroxy-3'-methoxyphenyl)-7-hydroxypropyl]benzene-2,4-diol) showed the most effective activity with an IC50 value of 35.1 microM, followed by compounds 2 [(8R,8'S)-7'-(3',4'-methylenedioxyphenyl)-8,8'-dimethyl-7-(3,4-dihydroxyphenyl)-butane] and 11 (malabaricone C) with IC50 values of 42.1 and 44.0 pM, respectively. This is the first report of significant anticholinesterase properties of M. fragrans seeds. The findings demonstrate that M. fragrans could be used beneficially in the treatment of Alzheimer's disease.

  11. Acetylcholinesterase Inhibitors on the Spinal Cord.

    DTIC Science & Technology

    1991-11-22

    NMDA and non-NMDA receptors are present at synapses between the dorsal root afferent neuron and the excitatory interneuron in the PSR and between the...that both NMDA and non-NMDA receptors are present at the synapses of both the afferent neuron and the excitatory interneuron in the PSR, and the...postsynaptic potentials,48 could be evoked synaptically by activation of glycinergic interneurons ,23 and exhibited conductance changes which can be mimicked by

  12. High resolution studies of complex solar active regions

    NASA Astrophysics Data System (ADS)

    Deng, Na

    Flares and Coronal Mass Ejections (CMEs) are energetic events, which can even impact the near-Earth environment and are the principal source of space weather. Most of them originate in solar active regions. The most violent events are produced in sunspots with a complex magnetic field topology. Studying their morphology and dynamics is helpful in understanding the energy accumulation and release mechanisms for flares and CMEs, which are intriguing problems in solar physics. The study of complex active regions is based on high-resolution observations from space missions and new instruments at the Big Bear Solar Observatory (BBSO). Adaptive optics (AO) in combination with image restoration techniques (speckle masking imaging) can achieve improved image quality and a spatial resolution (about 100 km on the solar surface) close to the diffraction limit of BBSO's 65 cm vacuum telescope. Dopplergrams obtained with a two-dimensional imaging spectrometer combined with horizontal flow maps derived with Local Correlation Tracking (LCT) provide precise measurements of the three-dimensional velocity field in sunspots. Magnetic field measurements from ground- and space-based instruments complement these data. At the outset of this study, the evolution and morphology of a typical round sunspot are described in some detail. The sunspot was followed from disk center to the limb, thus providing some insight into the geometry of the magnetic flux system. Having established a benchmark for a stable sunspot, the attention is turned to changes of the sunspot structure associated with flares and CMEs. Rapid penumbral decay and the strengthening of sunspot umbrae are manifestations of photospheric magnetic field changes after a flare. These sudden intensity changes are interpreted as a result of magnetic reconnection during the flare, which causes the magnetic field lines to be turned from more inclined to more vertical. Strong photospheric shear flows along the flaring magnetic

  13. Absence of substrate inhibition and freezing-inactivation of the mosquito acetylcholinesterase are caused by alterations of hydrophobic interactions.

    PubMed

    Dary, O; Wedding, R T

    1990-05-31

    Membrane-bound acetylcholinesterase (AChE) from mosquito showed the characteristic substrate inhibition of this enzyme, but 105,000 x g supernatants of freshly extracted enzyme did not. Addition of chaotropic anions, a freeze-thaw cycle and autolysis of the amphiphilic acetylcholinesterase to its non-amphiphilic derivatives resulted in return of the substrate inhibition feature along with an apparent increment in the enzyme activity. These results suggested that the lipidic environment of the mosquito AChE is temporarily perturbed when extracted. The enzyme is probably trapped in non-sedimenting mixtures composed of endogenous amphiphilic molecules. The occurrence of this phenomenon was not affected by the presence of Triton X-100 and other detergents, either alone or in combination with sodium chloride. Freezing in the presence of strong chaotropic anions (perchlorate, iodide and thiocyanate) caused the irreversible inactivation of the mosquito AChE. Crude and incomplete purified fractions of the enzyme were more sensitive than a more purified preparation. With both the purified AChE and the non-purified AChE, amphiphilic AChE was more freeze labile. Freezing at -10 degrees C enhanced inactivation of non-purified fractions. At this temperature, even weak chaotropic anions (fluoride, chloride and nitrate), while in combination with non-ionic detergents that solubilized mosquito AChE efficiently, reduced the enzyme activity of these fractions. In this case, recovery of the enzyme activity by incubation at 25 degrees C was inversely correlated with the effectiveness of the chaotropic anion. Gel filtration failed to show any change in the hydrodynamic radius of the freezing-inactivated AChE. Therefore, this phenomenon is explained as different degrees of denaturation of the enzyme in direct association with the chaotropic strength. Thus, antichaotropic anions, such as sulfate, should improve the stability of the mosquito acetylcholinesterase during extraction