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Sample records for boosting cholinergic activity

  1. Lipid modulation of neuronal cholinergic activity

    International Nuclear Information System (INIS)

    Phospholipids are the major lipids in the plasma membrane, and it is now evident that the function of phospholipids exceeds that of the role of barrier between different aqueous compartments. Several lines of evidence suggest that a major plasma membrane lipids, phosphatidylcholine, may be a useful compound for modulating presynaptic cholinergic transmission. In order to investigate the effects of PC on cholinergic terminals, rat cortical synaptosomes were preloaded with [3H]-ACh and then treated with small unilamellar vesicles (SUV) composed of dipalmitoylphosphatidylcholine (DPPC) at concentrations (0.8-1.5 mg/ml) similar to those found circulating in plasma. The effects of DPPC on levels, hydrolysis, release, and synthesis of [3H]-ACh were then examined. Dipalmitoylphosphatidylcholine decreased the levels of [3H]-ACh. This decrease does not result from a dilution of the radioactive [3H]-choline by nonradioactive choline derived from PC. Specifically, it is the S3 (cytoplasmic) level of [3H]-ACh that is decreased by DPPC treatment. This decrease appears to be partially due to lipid activation of an intraterminal cholinesterase which results in hydrolysis of nonvesicular [3H]-ACh. The ability of the lipid to interfere with exocytosis may account for the blockade of the K+ induced [3H]-ACh release from the P3 (vesicular) fraction. The high affinity choline transporter was competitively inhibited by DPPC treatment when synaptosomes were treated with DPPC prior to [3H]-choline loading; the ubiquitous low affinity transport was not affected. These effects were specific for cholinergic neurons since the uptake and release of dopamine and norepinephrine from the substantia nigra and the cortex, respectively, were not affected

  2. Regulation of drugs affecting striatal cholinergic activity by corticostriatal projections

    International Nuclear Information System (INIS)

    Research demonstrates that the chronic degeneration of the corticostriatal excitatory pathway makes the cholinergic neurons of the striatum insensitive to the neuropharmacological action of a number of different drugs. Female rats were used; they were killed and after the i.v. infusion of tritium-choline precursor, choline acetyltransferase activity was measured. Striatal noradrenaline, dopamine and serotonin content was measured by electrochemical detection coupled with high pressure liquid chromatography. Uptake of tritium-glutamic acid was estimated. The data were analyzed statistically. It is shown that there is evidence that the effects of a number of drugs capable of depressing cholinergic activity through receptor-mediated responses are operative only if the corticostriatal pathway is integral. Neuropharmacological responses in the brain appear to be the result of an interaction between several major neurotransmitter systems

  3. Optogenetic activation of cholinergic neurons in the PPT or LDT induces REM sleep

    OpenAIRE

    Van Dort, Christa J.; Zachs, Daniel P.; Kenny, Jonathan D.; Zheng, Shu; Goldblum, Rebecca R.; Gelwan, Noah A.; Ramos, Daniel M; Nolan, Michael A.; Wang, Karen; Weng, Feng-Ju; Lin, Yingxi; Wilson, Matthew A.; Emery N Brown

    2014-01-01

    Rapid eye movement (REM) sleep is a critical component of restful sleep, yet the mechanisms that control REM sleep are incompletely understood. Brainstem cholinergic neurons have been implicated in REM sleep regulation, but heterogeneous cell types in the area have made it difficult to determine the specific role of each population, leading to a debate about the importance of cholinergic neurons. Therefore, we selectively activated brainstem cholinergic neurons to determine their role in REM ...

  4. Cholinergic signal activated renin angiotensin system associated with cardiovascular changes in the ovine fetus

    OpenAIRE

    Geng, Chunsong; Mao, Caiping; Wu, Lei; Cheng, Yu; Liu, Rulu; Chen, Bingxin; Chen, Ling; Zhang, Lubo; Xu, Zhice

    2010-01-01

    Aim: Cholinergic regulation is important in the control of cardiovascular and endocrine responses. The mechanisms behind cardiovascular responses induced by cholinergic activation are explored by studying hormonal systems, including renin-angiotensin and vasopressin (VP). Results: In chronically prepared fetal sheep, intravenous infusion of the cholinergic agonist carbachol increased fetal systolic, diastolic, and mean arterial pressure accompanied with bradycardia at near-term. Although int...

  5. Selective Activation of Cholinergic Interneurons Enhances Accumbal Phasic Dopamine Release: Setting the Tone for Reward Processing

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    Roger Cachope

    2012-07-01

    Full Text Available Dopamine plays a critical role in motor control, addiction, and reward-seeking behaviors, and its release dynamics have traditionally been linked to changes in midbrain dopamine neuron activity. Here, we report that selective endogenous cholinergic activation achieved via in vitro optogenetic stimulation of nucleus accumbens, a terminal field of dopaminergic neurons, elicits real-time dopamine release. This mechanism occurs via direct actions on dopamine terminals, does not require changes in neuron firing within the midbrain, and is dependent on glutamatergic receptor activity. More importantly, we demonstrate that in vivo selective activation of cholinergic interneurons is sufficient to elicit dopamine release in the nucleus accumbens. Therefore, the control of accumbal extracellular dopamine levels by endogenous cholinergic activity results from a complex convergence of neurotransmitter/neuromodulator systems that may ultimately synergize to drive motivated behavior.

  6. Upregulating Nonneuronal Cholinergic Activity Decreases TNF Release from Lipopolysaccharide-Stimulated RAW264.7 Cells

    Directory of Open Access Journals (Sweden)

    Yi Lv

    2014-01-01

    Full Text Available Nonneuronal cholinergic system plays a primary role in maintaining homeostasis. It has been proved that endogenous neuronal acetylcholine (ACh could play an anti-inflammatory role, and exogenous cholinergic agonists could weaken macrophages inflammatory response to lipopolysaccharide (LPS stimulation through activation of α7 subunit-containing nicotinic acetylcholine receptor (α7nAChR. We assumed that nonneuronal cholinergic system existing in macrophages could modulate inflammation through autocrine ACh and expressed α7nAChR on the cells. Therefore, we explored whether LPS continuous stimulation could upregulate the nonneuronal cholinergic activity in macrophages and whether increasing autocrine ACh could decrease TNF release from the macrophages. The results showed that, in RAW264.7 cells incubated with LPS for 20 hours, the secretion of ACh was significantly decreased at 4 h and then gradually increased, accompanied with the enhancement of α7nAChR expression level. The release of TNF was greatly increased from RAW264.7 cells at 4 h and 8 h exposure to LPS; however, it was suppressed at 20 h. Upregulating choline acetyltransferase (ChAT expression through ChAT gene transfection could enhance ACh secretion and reduce TNF release from the infected RAW264. 7cells. The results indicated that LPS stimulation could modulate the activity of nonneuronal cholinergic system of RAW264.7 cells. Enhancing autocrine ACh production could attenuate TNF release from RAW264.7 cells.

  7. Urotensin II modulates rapid eye movement sleep through activation of brainstem cholinergic neurons

    DEFF Research Database (Denmark)

    Huitron-Resendiz, Salvador; Kristensen, Morten Pilgaard; Sánchez-Alavez, Manuel;

    2005-01-01

    dorsal tegmental nuclei. This distribution suggests that the UII system is involved in functions regulated by acetylcholine, such as the sleep-wake cycle. Here, we tested the hypothesis that UII influences cholinergic PPT neuron activity and alters rapid eye movement (REM) sleep patterns in rats. Local...

  8. Activation of vascular cholinergic and adrenergic receptors induced by gamma rays

    International Nuclear Information System (INIS)

    Activation of vascular cholinergic receptors and adrenoceptors plays an important role in vasomotoricity and peripheric vascular resistance. These factors are essential in maintaining a stable blood pressure. The aim of this study is to investigate the radiosensitivity differences between vascular cholinergic receptors and adrenoceptors, and consequently to determinate the effects of ionizing radiation (whole body irradiation) on contractile response regulation of vascular smooth muscle fibers VSMF isolated from rat portal vein. Our results show that Clonidine, (non-specific adrenergic agonist), and phenylephrine which is more specific α1-adrenoceptor agonist, increase the VSMF contractions. The maximum effect is obtained at 10-5 - 3.10-5 M. On irradiated rats (1-3-5 Gy), there is an important shift thus, the maximal response (Emax) can be obtained in lower concentrations of clonidine and phenylephrine. Irradiation deceases the contractile responses of VSMF mediated by cholinergic stimulation, in a dose dependant manner. With Emax 1 Gy>Emax 3 Gy>Emax 5 Gy. Irradiated muscular fibers became less sensitive to acetylcholine, thus 3.10-8 M. A. ch induced more than 50% of contraction force increase in normal conditions. This concentration induce generally a negligible effect after irradiation. The results reveal the existence of radiosensitivity differences between vascular cholinergic and adrenergic receptors. (author)

  9. Spontaneous Synaptic Activation of Muscarinic Receptors by Striatal Cholinergic Neuron Firing.

    Science.gov (United States)

    Mamaligas, Aphroditi A; Ford, Christopher P

    2016-08-01

    Cholinergic interneurons (CHIs) play a major role in motor and learning functions of the striatum. As acetylcholine does not directly evoke postsynaptic events at most striatal synapses, it remains unclear how postsynaptic cholinergic receptors encode the firing patterns of CHIs in the striatum. To examine the dynamics of acetylcholine release, we used optogenetics and paired recordings from CHIs and medium spiny neurons (MSNs) virally overexpressing G-protein-activated inwardly rectifying potassium (GIRK) channels. Due to the efficient coupling between endogenous muscarinic receptors and GIRK channels, we found that firing of individual CHIs resulted in monosynaptic spontaneous inhibitory post-synaptic currents (IPSCs) in MSNs. Paired CHI-MSN recordings revealed that the high probability of acetylcholine release at these synapses allowed muscarinic receptors to faithfully encode physiological activity patterns from individual CHIs without failure. These results indicate that muscarinic receptors in striatal output neurons reliably decode CHI firing. PMID:27373830

  10. Effectiveness of nootropic drugs with cholinergic activity in treatment of cognitive deficit: a review

    OpenAIRE

    Colucci, Luisa; Bosco, Massimiliano; Rosario Ziello, Antonio; Rea, Raffaele; Amenta, Francesco; Fasanaro, Angiola Maria

    2012-01-01

    Nootropics represent probably the first “smart drugs” used for the treatment of cognitive deficits. The aim of this paper is to verify, by a systematic analysis of the literature, the effectiveness of nootropics in this indication. The analysis was limited to nootropics with cholinergic activity, in view of the role played by acetylcholine in learning and memory. Acetylcholine was the first neurotransmitter identified in the history of neuroscience and is the main neurotransmitter of the peri...

  11. Cholinergic plasticity in the hippocampus

    OpenAIRE

    Colgin, Laura Lee; Kubota, Don; Lynch, Gary

    2003-01-01

    Tests were made for use-dependent plasticity in the cholinergic projections to hippocampus. Transient infusion of the cholinergic agonist carbachol into hippocampal slices induced rhythmic activity that persisted for hours after washout. Comparable effects were obtained with physostigmine, a drug that blocks acetylcholine breakdown and thereby enhances cholinergic transmission. It thus seems that activation of cholinergic synapses induces lasting changes in hippocampal physiology. Two lines o...

  12. Cholinergic-mediated IP3-receptor activation induces long-lasting synaptic enhancement in CA1 pyramidal neurons

    OpenAIRE

    Fernández de Sevilla, D.; Núñez Molina, Ángel; Borde, M.; Malinow, R.; Buño, Washinton

    2008-01-01

    Cholinergic-glutamatergic interactions influence forms of synaptic plasticity that are thought to mediate memory and learning. We tested in vitro the induction of long-lasting synaptic enhancement at Schaffer collaterals by acetylcholine (ACh) at the apical dendrite of CA1 pyramidal neurons and in vivo by stimulation of cholinergic afferents. In vitro ACh induced a Ca2+ wave and synaptic enhancement mediated by insertion of AMPA receptors in spines. Activation of muscarinic ACh receptors (mAC...

  13. Cuneiform neurons activated during cholinergically induced active sleep in the cat.

    Science.gov (United States)

    Pose, I; Sampogna, S; Chase, M H; Morales, F R

    2000-05-01

    In the present study, we report that the cuneiform (Cun) nucleus, a brainstem structure that before now has not been implicated in sleep processes, exhibits a large number of neurons that express c-fos during carbachol-induced active sleep (AS-carbachol). Compared with control (awake) cats, during AS-carbachol, there was a 671% increase in the number of neurons that expressed c-fos in this structure. Within the Cun nucleus, three immunocytochemically distinct populations of neurons were observed. One group consisted of GABAergic neurons, which predominantly did not express c-fos during AS-carbachol. Two other different populations expressed c-fos during this state. One of the Fos-positive (Fos(+)) populations consisted of a distinct group of nitric oxide synthase (NOS)-NADPH-diaphorase (NADPH-d)-containing neurons; the neurotransmitter of the other Fos(+) population remains unknown. The Cun nucleus did not contain cholinergic, catecholaminergic, serotonergic, or glycinergic neurons. On the basis of neuronal activation during AS-carbachol, as indicated by c-fos expression, we suggest that the Cun nucleus is involved, in an as yet unknown manner, in the physiological expression of active sleep. The finding of a population of NOS-NADPH-d containing neurons, which were activated during AS-carbachol, suggests that nitrergic modulation of their target cell groups is likely to play a role in active sleep-related physiological processes. PMID:10777795

  14. Cholinergic Enhancement of Frontal Lobe Activity in Mild Cognitive Impairment

    Science.gov (United States)

    Saykin, Andrew J.; Wishart, Heather A.; Rabin, Laura A.; Flashman, Laura A.; McHugh, Tara L.; Mamourian, Alexander C.; Santulli, Robert B.

    2004-01-01

    Cholinesterase inhibitors positively affect cognition in Alzheimer's disease (AD) and other conditions, but no controlled functional MRI studies have examined where their effects occur in the brain. We examined the effects of donepezil hydrochloride (Aricept[Registered sign]) on cognition and brain activity in patients with amnestic mild cognitive…

  15. Cholinergic activation enhances retinoic acid-induced differentiation in the human NB-4 acute promyelocytic leukemia cell line.

    Science.gov (United States)

    Chotirat, Sadudee; Suriyo, Tawit; Hokland, Marianne; Hokland, Peter; Satayavivad, Jutamaad; Auewarakul, Chirayu U

    2016-07-01

    The non-neuronal cholinergic system (NNCS) has been shown to play a role in regulating hematopoietic differentiation. We determined the expression of cholinergic components in leukemic cell lines by Western blotting and in normal leukocyte subsets by flow cytometry and found a heterogeneous expression of choline acetyltransferase (ChAT), acetylcholinesterase (AChE), choline transporter (CHT), M3 muscarinic acetylcholine receptor (M3-mAChR) and α7 nicotinic acetylcholine receptor (α7-nAChR). We then evaluated NNCS role in differentiation of human NB-4 acute promyelocytic leukemia cell line and discovered a dramatic induction of M3-mAChR after all-trans retinoic acid (ATRA) treatment (p<0.0001). Adding carbachol which is a cholinergic agonist to the ATRA treatment resulted in an increase of a granulocytic differentiation marker (CD11b) as compared with ATRA treatment alone (p<0.05), indicating that cholinergic activation enhanced ATRA in inducing NB-4 maturation. The combination of carbachol and ATRA treatment for 72h also resulted in decreased viability and increased cleaved caspase-3 expression when compared with ATRA treatment alone (p<0.05). However, this combination did not cause poly (ADP-ribose) polymerase (PARP) cleavage. Overall, we have shown that NB-4 cells expressed M3-mAChR in a differentiation-dependent manner and cholinergic stimulation induced maturation and death of ATRA-induced differentiated NB-4 cells. PMID:27282572

  16. Increased dopamine D1 receptor binding in the human mesocortical system following central cholinergic activation

    International Nuclear Information System (INIS)

    Full text: The interaction between the cholinergic and dopaminergic system has been implicated in many pathological processes including, Alzheimer's disease, schizophrenia and drug addiction. Little is known about the control of dopamine (DA) release following central cholinergic activation in humans, but experimental studies suggest that endogenously released Acetylcholine (ACh) achieved by the administration of cholinesterase inhibitors, can increase dopamine efflux in different regions of the brain. This leads to the activation of different types of post-synaptic dopaminergic receptors which belong to the family of G-protein coupled receptors (GPCRs). A common paradigm of the GPCRs desensitization is that agonist-induced receptor signaling is rapidly attenuated by receptor internalisation. Several experiments have shown that the activation of Dl receptors in acute conditions leads, within minutes, to translocation of the receptor from the surface of the neurons to the endosomal compartment in the cytoplasm and increased receptor turnover. To assess changes in Dl receptor density following an intravenous infusion of the selective cholinesterase inhibitor physostigmine salicylate (PHY), we studied eleven normal subjects (10 male and 1 female, mean age 36.1 and 61617; 9.9) using [11C]-SCH23390 and PET The binding potential (BP) for SCH23390 was significantly (p0.05). There was no statistically significant difference between baseline and physostigmine Kl ratio (p>0.05) suggesting that BP changes observed were not secondary to regional blood flow changes or to an order effect of the scans. Copyright (2002) The Australian and New Zealand Society of Nuclear Medicine Inc

  17. Non-cholinergic component of rat splanchnic nerves predominates at low neuronal activity and is eliminated by naloxone.

    Science.gov (United States)

    Malhotra, R K; Wakade, A R

    1987-02-01

    M-tetraethylammonium; higher concentrations of naloxone (100 microM) were also ineffective. 7. It is concluded that neurally evoked secretion of catecholamines is mediated by acetylcholine and a non-cholinergic substance(s); the contribution of non-cholinergic substance(s) predominates at low neuronal activity, whereas that of acetylcholine is maximum at high neuronal activity. Blockade of the non-cholinergic component by naloxone suggests that an opioid peptide may be involved in the secretion of catecholamines in the rat adrenal medulla. PMID:3656137

  18. Cholinergic pairing with visual activation results in long-term enhancement of visual evoked potentials.

    Directory of Open Access Journals (Sweden)

    Jun Il Kang

    Full Text Available Acetylcholine (ACh contributes to learning processes by modulating cortical plasticity in terms of intensity of neuronal activity and selectivity properties of cortical neurons. However, it is not known if ACh induces long term effects within the primary visual cortex (V1 that could sustain visual learning mechanisms. In the present study we analyzed visual evoked potentials (VEPs in V1 of rats during a 4-8 h period after coupling visual stimulation to an intracortical injection of ACh analog carbachol or stimulation of basal forebrain. To clarify the action of ACh on VEP activity in V1, we individually pre-injected muscarinic (scopolamine, nicotinic (mecamylamine, alpha7 (methyllycaconitine, and NMDA (CPP receptor antagonists before carbachol infusion. Stimulation of the cholinergic system paired with visual stimulation significantly increased VEP amplitude (56% during a 6 h period. Pre-treatment with scopolamine, mecamylamine and CPP completely abolished this long-term enhancement, while alpha7 inhibition induced an instant increase of VEP amplitude. This suggests a role of ACh in facilitating visual stimuli responsiveness through mechanisms comparable to LTP which involve nicotinic and muscarinic receptors with an interaction of NMDA transmission in the visual cortex.

  19. Cholinergic Enhancement of Brain Activation in Mild Cognitive Impairment (MCI during Episodic Memory Encoding

    Directory of Open Access Journals (Sweden)

    Shannon L Risacher

    2013-09-01

    Full Text Available Objective: To determine the physiological impact of treatment with donepezil (Aricept on neural circuitry supporting episodic memory encoding in patients with amnestic mild cognitive impairment (MCI using functional MRI (fMRI. Methods: 18 patients with MCI and 20 age-matched healthy controls (HC were scanned twice while performing an event-related verbal episodic encoding task. MCI participants were scanned before treatment and after approximately 3 months on donepezil; HC were untreated but rescanned at the same interval. Voxel-level analyses assessed treatment effects in activation profile relative to retest changes in non-treated HC. Changes in task-related connectivity in medial temporal circuitry were also evaluated, as were associations between brain activation pattern, task-related functional connectivity, task performance, and clinical measures of cognition.Results: At baseline, the MCI group showed reduced activation during encoding relative to HC in the right medial temporal lobe (MTL; hippocampal/parahippocampal and additional regions, as well as attenuated task-related deactivation, relative to rest, in a medial parietal lobe cluster. After treatment, the MCI group showed normalized MTL activation and improved parietal deactivation. These changes were associated with cognitive performance. After treatment, the MCI group also demonstrated increased task-related functional connectivity from the right MTL cluster seed region to a network of other sites including the basal nucleus/caudate and bilateral frontal lobes. Increased functional connectivity was associated with improved task performance.Conclusions: Pharmacologic enhancement of cholinergic function in amnestic MCI is associated with changes in brain activation pattern and functional connectivity during episodic memory processing which are in turn related to increased cognitive performance. fMRI is a promising biomarker for assessing treatment related changes in brain function.

  20. EVALUATION OF ANTI-CHOLINERGIC AND ANTI-ANAPHYLACTIC ACTIVITY OF SHIRISHADI POLYHERBAL COMPOUND

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    Kajaria Divya

    2012-02-01

    Full Text Available Asthma is a chronic inflammatory disease of airways with widespread narrowing of air passage which may be relieved spontaneously or as a result of therapy and, clinically it is characterized by paroxysms of dyspnea, cough and wheezing. Inflammation and broncho-constriction are the two major hallmarks in the pathology of Asthma. Shirishadi is a polyherbal drug used in the management of bronchial asthma by Ayurvedic practitioners from decades. Shirisha (Albezzia lebbeck, Nagarmotha (Cyprus rotandus and Kantakari (Solanum xanthocarpum are the ingredient herbs of this compound. Hence, the present investigation was undertaken to evaluate the bronchodilator and anti-anaphylactic activity of Shirishadi Polyherbal compound. Experimental models studied were egg albumin induced anaphylaxis in guinea pigs and Anti-Cholinergic activity was studied on Isolated Frog Heart and Frog Rectus Muscle. The extract produced 30+ 0.23% inhibition in maximum contraction produced by Acetylcholine which is much less than that produced by standard drug (99.9%, moreover the dose of extract that produced the visible effect is much higher than that used for therapeutic purpose suggesting that antiasthmatic effect of drug is not due to Acetylcholine antagonism activity. Neither Acetylcholine efficacy nor its potency decreases significantly with increasing dose of drug. Drug increased the cardiac tone and stimulate the cardiac contractility but unable to prevail over complete inhibition of heart rate produced by Acetylcholine. The drug produced significant protection against egg albumin induced anaphylactic shock characterized by decrease in intensity and delay in the development of symptoms of dyspnoea, asphyxia and collapse. All these findings reveal the bronchodilator and anti-anaphylactic activity of Shirishadi compound indicating its beneficial use in asthma.

  1. Activities of cholinergic proteins in APP/PS1 double transgenic mice

    Czech Academy of Sciences Publication Activity Database

    Málková, Barbora; Machová, Eva; Jakubík, Jan; Doležal, Vladimír

    Fyziologický ústav AV ČR, v. v. i.. Roč. 54, č. 3 (2005), 31P-31P ISSN 0862-8408. [Physiological Days /81./. 02.02.2005-04.02.2005, Košice] R&D Projects: GA AV ČR(CZ) IAA5011306; GA ČR(CZ) IAA5011206 Institutional research plan: CEZ:AV0Z5011922 Keywords : cholinergic neuron * APP/PS1 transgenic mice * cholinergic markers * Alzheimer ´s disease Subject RIV: ED - Physiology

  2. Central muscarinic cholinergic activation alters interaction between splenic dendritic cell and CD4+CD25- T cells in experimental colitis.

    Directory of Open Access Journals (Sweden)

    Peris Munyaka

    Full Text Available BACKGROUND: The cholinergic anti-inflammatory pathway (CAP is based on vagus nerve (VN activity that regulates macrophage and dendritic cell responses in the spleen through alpha-7 nicotinic acetylcholine receptor (a7nAChR signaling. Inflammatory bowel disease (IBD patients present dysautonomia with decreased vagus nerve activity, dendritic cell and T cell over-activation. The aim of this study was to investigate whether central activation of the CAP alters the function of dendritic cells (DCs and sequential CD4+/CD25-T cell activation in the context of experimental colitis. METHODS: The dinitrobenzene sulfonic acid model of experimental colitis in C57BL/6 mice was used. Central, intracerebroventricular infusion of the M1 muscarinic acetylcholine receptor agonist McN-A-343 was used to activate CAP and vagus nerve and/or splenic nerve transection were performed. In addition, the role of α7nAChR signaling and the NF-kB pathway was studied. Serum amyloid protein (SAP-A, colonic tissue cytokines, IL-12p70 and IL-23 in isolated splenic DCs, and cytokines levels in DC-CD4+CD25-T cell co-culture were determined. RESULTS: McN-A-343 treatment reduced colonic inflammation associated with decreased pro-inflammatory Th1/Th17 colonic and splenic cytokine secretion. Splenic DCs cytokine release was modulated through α7nAChR and the NF-kB signaling pathways. Cholinergic activation resulted in decreased CD4+CD25-T cell priming. The anti-inflammatory efficacy of central cholinergic activation was abolished in mice with vagotomy or splenic neurectomy. CONCLUSIONS: Suppression of splenic immune cell activation and altered interaction between DCs and T cells are important aspects of the beneficial effect of brain activation of the CAP in experimental colitis. These findings may lead to improved therapeutic strategies in the treatment of IBD.

  3. Adrenergic and cholinergic activity contributes to the cardiovascular effects of lionfish (Pterois volitans) venom.

    Science.gov (United States)

    Church, Jarrod E; Hodgson, Wayne C

    2002-06-01

    The aim of the present study was to further investigate the cardiovascular activity of Pterois volitans crude venom. Venom (0.6-18 microg protein/ml) produced dose- and endothelium-dependent relaxation in porcine coronary arteries that was potentiated by atropine (10nM), but significantly attenuated by the nitric oxide synthase inhibitor N(omega)-nitro-L-arginine (NOLA; 0.1mM), by prior exposure of the tissue to stonefish antivenom (SFAV, 3 units/ml, 10 min), or by removal of extracellular Ca(2+). In rat paced left atria, venom (10 microg protein/ml) produced a decrease, followed by an increase, in contractile force. Atropine (0.5 microM) abolished the decrease in force and potentiated the increase. Propranolol (5 microM) did not affect the decrease in force but significantly attenuated the increase. In spontaneously beating right atria, venom (10 microg protein/ml) produced an increase in rate that was significantly attenuated by propranolol (5 microM). Prior incubation with SFAV (0.3 units/microg protein, 10 min) abolished both the inotropic and chronotropic responses to venom. In the anaesthetised rat, venom (100 micro protein/kg, i.v.) produced a pressor response, followed by a sustained depressor response. Atropine (1mg/kg, i.v.) potentiated the pressor response. The further addition of prazosin (50 microg/kg, i.v.) restored the original response to venom. Prior administration of SFAV (100 units/kg, i.v., 10 min) significantly attenuated the in vivo response to venom. It is concluded that P. volitans venom produces its cardiovascular effects primarily by acting on muscarinic cholinergic receptors and adrenoceptors. As SFAV neutralised many of the effects of P. volitans venom, we suggest that the two venoms share a similar component(s). PMID:12175616

  4. Puerarin partly counteracts the inflammatory response after cerebral ischemia/reperfusion via activating the cholinergic anti-inflammatory pathway

    Institute of Scientific and Technical Information of China (English)

    Xiaojie Liu; Zhigang Mei; Jingping Qian; Yongbao Zeng; Mingzhi Wang

    2013-01-01

    Puerarin, a major isoflavonoid derived from the Chinese medical herb radix puerariae (Gegen), has been reported to inhibit neuronal apoptosis and play an anti-inflammatory role in focal cerebral ischemia model rats. Recent findings regarding stroke pathophysiology have recognized that an-ti-inflammation is an important target for the treatment of ischemic stroke. The cholinergic an-ti-inflammatory pathway is a highly robust neural-immune mechanism for inflammation control. This study was to investigate whether activating the cholinergic anti-inflammatory pathway can be in-volved in the mechanism of inhibiting the inflammatory response during puerarin-induced cerebral ischemia/reperfusion in rats. Results showed that puerarin pretreatment (intravenous injection) re-duced the ischemic infarct volume, improved neurological deficit after cerebral ischemia/reperfusion and decreased the levels of interleukin-1β, interleukin-6 and tumor necrosis factor-αin brain tissue. Pretreatment with puerarin (intravenous injection) attenuated the inflammatory response in rats, which was accompanied by janus-activated kinase 2 (JAK2) and signal transducers and activators of transcription 3 (STAT3) activation and nuclear factor kappa B (NF-κB) inhibition. These observa-tions were inhibited by the alpha7 nicotinic acetylcholine receptor (α7nAchR) antagonistα-bungarotoxin (α-BGT). In addition, puerarin pretreatment increased the expression of α7nAchR mRNA in ischemic cerebral tissue. These data demonstrate that puerarin pretreatment strongly protects the brain against cerebral ischemia/reperfusion injury and inhibits the inflammatory re-sponse. Our results also indicated that the anti-inflammatory effect of puerarin may partly be me-diated through the activation of the cholinergic anti-inflammatory pathway.

  5. c-fos Expression in mesopontine noradrenergic and cholinergic neurons of the cat during carbachol-induced active sleep: a double-labeling study.

    Science.gov (United States)

    Yamuy, J; Sampogna, S; Morales, F R; Chase, M H

    1998-01-01

    The interaction of cholinergic and catecholaminergic mechanisms in the mesopontine region has been hypothesized as being critical for the generation and maintenance of active (REM) sleep. To further examine this hypothesis, we sought to determine the pattern of neuronal activation (via c-fos expression) of catecholaminergic and cholinergic neurons in this region during active sleep induced by the pontine microapplication of carbachol (designated as active sleep-carbachol). Accordingly, we used two sets of double-labeling techniques; the first to identify tyrosine hydroxylase-containing neurons (putative catecholaminergic cells) which also express the c-fos protein product Fos, and the second to reveal choline acetyltransferase-containing neurons (putative cholinergic cells) which also express Fos. Compared to control cats, active sleep-carbachol cats exhibited a significantly greater number of Fos-expressing neurons in the dorsolateral region of the pons, which encompasses the locus coeruleus, the lateral pontine reticular formation, the peribrachial nuclei and the latero-dorsal and pedunculo-pontine tegmental nuclei. However, both control and active sleep-carbachol cats exhibited a similar number of catecholaminergic and cholinergic neurons in those regions that expressed Fos (i.e., double-labeled cells). A large number of c-fos-expressing neurons in the active sleep-carbachol cats whose neurotransmitter phenotype was not identified suggests that non-catecholaminergic, non-cholinergic neuronal populations in mesopontine regions are involved in the generation and maintenance of active sleep. The lack of increased c-fos expression in catecholaminergic neurons during active sleep-carbachol confirms and extends previous data that indicate that these cells are silent during active sleep-carbachol and naturally-occurring active sleep. The finding that cholinergic neurons of the dorsolateral pons were not activated either during wakefulness or active sleep

  6. Comparative Study of Korean White, Red, and Black Ginseng Extract on Cholinesterase Inhibitory Activity and Cholinergic Function

    OpenAIRE

    Lee, Mi Ra; Yun, Beom Sik; In, Oh Hyun; Sung, Chang Keun

    2011-01-01

    This study evaluated cholineresterase inhibitory activity of Korean white ginseng extract (WGE), red ginseng extract (RGE), and black ginseng extract (BGE) and the cholinergic effect on scopolamine (SCOP)-induced amnesic mice. WGE, RGE, and BGE inhibited acetylcholineserase (AChE), as well as butyrylcholineserase (BuChE) in a concentration-dependent manner. BGE presented strong inhibition of AChE with an IC50 value of 1.72 mg/mL, followed by WGE (5.89 mg/mL), RGE (6.30 mg/mL), respectively. T...

  7. Impairment of cognitive function and reduced hippocampal cholinergic activity in a rat model of chronic intermittent hypoxia

    Institute of Scientific and Technical Information of China (English)

    Chunling Zhao; Yan Chen; Chunlai Zhang; Linya Lü; Qian Xu

    2011-01-01

    The present study established a rat model of chronic intermittent hypoxia (CIH) to simulate obstructive sleep apnea syndrome. CIH rats were evaluated for cognitive function using the Morris water maze, and neuronal pathology in the hippocampus was observed using hematoxylin-eosin staining. In addition, hippocampal choline acetyl transferase (ChAT) and nicotinic acetylcholine receptor (nAChR) expression was determined by immunohistochemistry. Our results revealed necrotic hippocampal neurons, decreased ChAT and nAChR expression, as well as cognitive impairment in CIH rats. These results suggest that hippocampal neuronal necrosis and decreased cholinergic activity may be involved in CIH-induced cognitive impairment in rats.

  8. Optogenetic activation of striatal cholinergic interneurons regulates L-dopa-induced dyskinesias.

    Science.gov (United States)

    Bordia, Tanuja; Perez, Xiomara A; Heiss, Jaime E; Zhang, Danhui; Quik, Maryka

    2016-07-01

    L-dopa-induced dyskinesias (LIDs) are a serious complication of L-dopa therapy for Parkinson's disease. Emerging evidence indicates that the nicotinic cholinergic system plays a role in LIDs, although the pathways and mechanisms are poorly understood. Here we used optogenetics to investigate the role of striatal cholinergic interneurons in LIDs. Mice expressing cre-recombinase under the control of the choline acetyltransferase promoter (ChAT-Cre) were lesioned by unilateral injection of 6-hydroxydopamine. AAV5-ChR2-eYFP or AAV5-control-eYFP was injected into the dorsolateral striatum, and optical fibers implanted. After stable virus expression, mice were treated with L-dopa. They were then subjected to various stimulation protocols for 2h and LIDs rated. Continuous stimulation with a short duration optical pulse (1-5ms) enhanced LIDs. This effect was blocked by the general muscarinic acetylcholine receptor (mAChR) antagonist atropine indicating it was mAChR-mediated. By contrast, continuous stimulation with a longer duration optical pulse (20ms to 1s) reduced LIDs to a similar extent as nicotine treatment (~50%). The general nicotinic acetylcholine receptor (nAChR) antagonist mecamylamine blocked the decline in LIDs with longer optical pulses showing it was nAChR-mediated. None of the stimulation regimens altered LIDs in control-eYFP mice. Lesion-induced motor impairment was not affected by optical stimulation indicating that cholinergic transmission selectively regulates LIDs. Longer pulse stimulation increased the number of c-Fos expressing ChAT neurons, suggesting that changes in this immediate early gene may be involved. These results demonstrate that striatal cholinergic interneurons play a critical role in LIDs and support the idea that nicotine treatment reduces LIDs via nAChR desensitization. PMID:26921469

  9. Boosting visual cortex function and plasticity with acetylcholine to enhance visual perception

    Directory of Open Access Journals (Sweden)

    Jun-Il eKang

    2014-09-01

    Full Text Available The cholinergic system is a potent neuromodulatory system that plays critical roles in cortical plasticity, attention and learning. In this review, we propose that the cellular effects of acetylcholine in the primary visual cortex during the processing of visual inputs might induce perceptual learning; i.e., long-term changes in visual perception. Specifically, the pairing of cholinergic activation with visual stimulation increases the signal-to-noise ratio, cue detection ability and long-term facilitation in the primary visual cortex. This cholinergic enhancement would increasesthe strength of thalamocortical afferents to facilitate the treatment of a novel stimulus while decreasing the cortico-cortical signaling to reduce recurrent or top-down modulation. This balance would be mediated by different cholinergic receptor subtypes that are located on both glutamatergic and GABAergic neurons of the different cortical layers. The mechanisms of cholinergic enhancement are closely linked to attentional processes, long-term potentiation and modulation of the excitatory/inhibitory balance. Recently, it was found that boosting this system during visual training robustly enhances sensory perception in a long-term manner. Our hypothesis is that repetitive pairing of cholinergic and sensory stimulation over a long period of time induces long-term changes in the processing of trained stimuli that might improve perceptual ability. Various non-invasive approaches to the activation of the cholinergic neurons have strong potential to improve visual perception.

  10. Locality-dependent descending reflex motor activity in the anal canal-cholinergic and nitrergic contributions in the rat model

    Institute of Scientific and Technical Information of China (English)

    Radomir RADOMIROV; Christina IVANCHEVA; Dimitar ITZEV; Polina PETKOVA-KIROVA

    2009-01-01

    Aim: Since the distal part of the intestine is targeted by a wide range of pathogens, the motility of the recto-anal region has been the object of many experimental and clinical observations. In this study, we investigated descending motor responses in the anal canal as a measure of the activation of autonomic reflex pathways underlying evacuatory recto-anal activity. Methods: The partitioned organ bath method was used to register motor responses of the anal canal as induced by balloon distension of the rectum in isolated rat recto-anal preparations. Results: Distension-induced descending responses of the anal canal comprised contractions (with distension at a distance of 15 mm), initial contractions and secondary relaxations (at 10 mm) and short contractions followed by deep relaxations (at 3-5 mm). Decreas-ing the distance between the distension stimulus and the anal canal resulted in a decreased contraction response and increased relaxation. Tetrodotoxin (0.1 μmol/L) inhibited these responses. Atropine (0.3 μmol/L) decreased contraction and did not change the relaxation response. N~G-nitro-L-arginine (0.5 mmol/L) enhanced contraction in both the absence and presence of atropine. L-arginine (0.5 mmol/L) inhibited contraction and extended relaxation in atropine-pretreated preparations. The actions of N~G-nitro-L-arginine and L-arginine were more pronounced in the aboral direction. ChAT-positive nerve fibers were observed in myenteric ganglia of the rectum and the anal canal. The density of NADPH-diaphorase-positive neurons was higher in the anal canal region. Conclusion: Our results suggest that locality-dependent activation of the descending reflex neuromuscular communications underlie evacuatory activity in the recto-anal region. This activation response involves long excitatory cholinergic and non-cholinergic pathways along the rectum and short inhibitory nitrergic pathways located predominantly in the anal canal region.

  11. Nitrergic ventro-medial medullary neurons activated during cholinergically induced active (REM) sleep in the cat

    OpenAIRE

    Pose, Inés; Sampogna, Sharon; Chase, Michael H.; Morales, Francisco R.

    2010-01-01

    The rostral ventro-medial medullary reticular formation is a complex structure that is involved with a variety of motor functions. It contains glycinergic neurons that are activated during active (REM) sleep (AS); these neurons appear to be responsible for the postsynaptic inhibition of motoneurons that occurs during this state. We have reported that neurons in this same region contain nitric oxide (NO) synthase and that they innervate brainstem motor pools. In the present study we examined t...

  12. Cholinesterases: structure of the active site and mechanism of the effect of cholinergic receptor blockers on the rate of interaction with ligands

    International Nuclear Information System (INIS)

    Modern views on the structure of cholinesterase active sites and the mechanism of their interaction with organophosphorus inhibitors are considered. The attention is focused on the mechanism of the effect of cholinergic receptor blockers, acetylcholine antagonists, on the rate of interaction of acetylcholine esterase with organophosphorus inhibitors.

  13. Low-level microwave irradiations affect central cholinergic activity in the rat

    Energy Technology Data Exchange (ETDEWEB)

    Lai, H.; Horita, A.; Chou, C.K.; Guy, A.W.

    1987-01-01

    Sodium-dependent high-affinity choline uptake was measured in various regions of the brains of rats irradiated for 45 min with either pulsed or continuous-wave low-level microwaves (2,450 MHz; power density, 1 mW/cm2; average whole-body specific absorption rate, 0.6 W/kg). Pulsed microwave irradiation (2-microseconds pulses, 500 pulses/s) decreased choline uptake in the hippocampus and frontal cortex but had no significant effect on the hypothalamus, striatum, and inferior colliculus. Pretreatment with a narcotic antagonist (naloxone or naltrexone; 1 mg/kg i.p.) blocked the effect of pulsed microwaves on hippocampal choline uptake but did not significantly alter the effect on the frontal cortex. Irradiation with continuous-wave microwaves did not significantly affect choline uptake in the hippocampus, striatum, and hypothalamus but decreased the uptake in the frontal cortex. The effect on the frontal cortex was not altered by pretreatment with narcotic antagonist. These data suggest that exposure to low-level pulsed or continuous-wave microwaves leads to changes in cholinergic functions in the brain.

  14. Elimination of the vesicular acetylcholine transporter in the striatum reveals regulation of behaviour by cholinergic-glutamatergic co-transmission.

    Science.gov (United States)

    Guzman, Monica S; De Jaeger, Xavier; Raulic, Sanda; Souza, Ivana A; Li, Alex X; Schmid, Susanne; Menon, Ravi S; Gainetdinov, Raul R; Caron, Marc G; Bartha, Robert; Prado, Vania F; Prado, Marco A M

    2011-11-01

    Cholinergic neurons in the striatum are thought to play major regulatory functions in motor behaviour and reward. These neurons express two vesicular transporters that can load either acetylcholine or glutamate into synaptic vesicles. Consequently cholinergic neurons can release both neurotransmitters, making it difficult to discern their individual contributions for the regulation of striatal functions. Here we have dissected the specific roles of acetylcholine release for striatal-dependent behaviour in mice by selective elimination of the vesicular acetylcholine transporter (VAChT) from striatal cholinergic neurons. Analysis of several behavioural parameters indicates that elimination of VAChT had only marginal consequences in striatum-related tasks and did not affect spontaneous locomotion, cocaine-induced hyperactivity, or its reward properties. However, dopaminergic sensitivity of medium spiny neurons (MSN) and the behavioural outputs in response to direct dopaminergic agonists were enhanced, likely due to increased expression/function of dopamine receptors in the striatum. These observations indicate that previous functions attributed to striatal cholinergic neurons in spontaneous locomotor activity and in the rewarding responses to cocaine are mediated by glutamate and not by acetylcholine release. Our experiments demonstrate how one population of neurons can use two distinct neurotransmitters to differentially regulate a given circuitry. The data also raise the possibility of using VAChT as a target to boost dopaminergic function and decrease high striatal cholinergic activity, common neurochemical alterations in individuals affected with Parkinson's disease. PMID:22087075

  15. Elimination of the vesicular acetylcholine transporter in the striatum reveals regulation of behaviour by cholinergic-glutamatergic co-transmission.

    Directory of Open Access Journals (Sweden)

    Monica S Guzman

    2011-11-01

    Full Text Available Cholinergic neurons in the striatum are thought to play major regulatory functions in motor behaviour and reward. These neurons express two vesicular transporters that can load either acetylcholine or glutamate into synaptic vesicles. Consequently cholinergic neurons can release both neurotransmitters, making it difficult to discern their individual contributions for the regulation of striatal functions. Here we have dissected the specific roles of acetylcholine release for striatal-dependent behaviour in mice by selective elimination of the vesicular acetylcholine transporter (VAChT from striatal cholinergic neurons. Analysis of several behavioural parameters indicates that elimination of VAChT had only marginal consequences in striatum-related tasks and did not affect spontaneous locomotion, cocaine-induced hyperactivity, or its reward properties. However, dopaminergic sensitivity of medium spiny neurons (MSN and the behavioural outputs in response to direct dopaminergic agonists were enhanced, likely due to increased expression/function of dopamine receptors in the striatum. These observations indicate that previous functions attributed to striatal cholinergic neurons in spontaneous locomotor activity and in the rewarding responses to cocaine are mediated by glutamate and not by acetylcholine release. Our experiments demonstrate how one population of neurons can use two distinct neurotransmitters to differentially regulate a given circuitry. The data also raise the possibility of using VAChT as a target to boost dopaminergic function and decrease high striatal cholinergic activity, common neurochemical alterations in individuals affected with Parkinson's disease.

  16. Activation of the mouse primary visual cortex by medial prefrontal subregion stimulation is not mediated by cholinergic basalo-cortical projections

    Directory of Open Access Journals (Sweden)

    Hoang Nam Nguyen

    2015-02-01

    Full Text Available The medial prefrontal cortex (mPFC exerts top-down control of primary visual cortex (V1 activity. As there is no direct neuronal projection from mPFC to V1, this functional connection may use an indirect route, i.e., via basalo-cortical cholinergic projections. The cholinergic projections to V1 originate from neurons in the horizontal limb of the diagonal band of Broca (HDB, which receive neuronal projections from the ventral part of the mPFC, composed of prelimbic (PrL and infralimbic cortices (IL. Therefore, the objective of this study was to determine whether electrical stimulation of mice mPFC subregions activate 1 V1 neurons and 2 HDB cholinergic neurons, suggesting that the HDB serves as a relay point in the mPFC-V1 interaction. Neuronal activation was quantified using c-Fos immunocytochemistry or thallium autometallography for each V1 layer using automated particle analysis tools and optical density measurement. Stimulation of IL and PrL induced significantly higher c-Fos expression or thallium labelling in layers II/III and V of V1 in the stimulated hemisphere only. A HDB cholinergic neuron-specific lesion by saporin administration reduced IL-induced c-Fos expression in layers II/III of V1 but not in layer V. However, there was no c-Fos expression or thallium labelling in the HDB neurons, suggesting that this area was not activated by IL stimulation. Stimulation of another mPFC subarea, the anterior cingulate cortex (AC, which is involved in attention and receives input from V1, activated neither V1 nor HDB. The present results indicate that IL and PrL, but not AC, stimulation activates V1 with the minor involvement of the HDB cholinergic projections. These results suggest a functional link between the ventral mPFC and V1, but this function is only marginally supported by HDB cholinergic neurons and may involve other brain regions.

  17. Structure and boosting activity of a starch-degrading lytic polysaccharide monooxygenase

    DEFF Research Database (Denmark)

    Lo Leggio, Leila; Simmons, Thomas J.; Poulsen, Jens-Christian Navarro;

    2015-01-01

    Lytic polysaccharide monooxygenases (LPMOs) are recently discovered enzymes that oxidatively deconstruct polysaccharides. LPMOs are fundamental in the effective utilization of these substrates by bacteria and fungi; moreover, the enzymes have significant industrial importance. We report here the...... activity, spectroscopy and three-dimensional structure of a starch-active LPMO, a representative of the new CAZy AA13 family. We demonstrate that these enzymes generate aldonic acid-terminated malto-oligosaccharides from retrograded starch and boost significantly the conversion of this recalcitrant...

  18. Activation of the reward system boosts innate and adaptive immunity.

    Science.gov (United States)

    Ben-Shaanan, Tamar L; Azulay-Debby, Hilla; Dubovik, Tania; Starosvetsky, Elina; Korin, Ben; Schiller, Maya; Green, Nathaniel L; Admon, Yasmin; Hakim, Fahed; Shen-Orr, Shai S; Rolls, Asya

    2016-08-01

    Positive expectations contribute to the clinical benefits of the placebo effect. Such positive expectations are mediated by the brain's reward system; however, it remains unknown whether and how reward system activation affects the body's physiology and, specifically, immunity. Here we show that activation of the ventral tegmental area (VTA), a key component of the reward system, strengthens immunological host defense. We used 'designer receptors exclusively activated by designer drugs' (DREADDs) to directly activate dopaminergic neurons in the mouse VTA and characterized the subsequent immune response after exposure to bacteria (Escherichia coli), using time-of-flight mass cytometry (CyTOF) and functional assays. We found an increase in innate and adaptive immune responses that were manifested by enhanced antibacterial activity of monocytes and macrophages, reduced in vivo bacterial load and a heightened T cell response in the mouse model of delayed-type hypersensitivity. By chemically ablating the sympathetic nervous system (SNS), we showed that the reward system's effects on immunity are, at least partly, mediated by the SNS. Thus, our findings establish a causal relationship between the activity of the VTA and the immune response to bacterial infection. PMID:27376577

  19. Electroacupuncture-Induced Cholinergic Nerve Activation Enhances the Hypoglycemic Effect of Exogenous Insulin in a Rat Model of Streptozotocin-Induced Diabetes

    Directory of Open Access Journals (Sweden)

    Yu-Chen Lee

    2011-01-01

    Full Text Available The aim of this study is to explore the mechanisms by which electroacupuncture (EA enhances the hypoglycemic effect of exogenous insulin in a streptozotocin- (STZ- diabetic rats. Animals in the EA group were anesthetized and subjected to the insulin challenge test (ICT and EA for 60 minutes. In the control group, rats were subjected to the same treatment with the exception of EA stimulation. Blood samples were drawn to measure changes in plasma glucose, free fatty acids (FFA, and insulin levels. Western blot was used to assay proteins involved in insulin signaling. Furthermore, atropine, hemicholinium-3 (HC-3, and Eserine were used to explore the relationship between EA and cholinergic nerve activation during ICT. EA augmented the blood glucose-lowering effects of EA by activating the cholinergic nerves in STZ rats that had been exposed to exogenous insulin. This phenomenon may be related to enhancement of insulin signaling rather than to changes in FFA concentration.

  20. Dexmedetomidine attenuates inflammatory reaction in the lung tissues of septic mice by activating cholinergic anti-inflammatory pathway.

    Science.gov (United States)

    Liu, Zhaoguo; Wang, Yueping; Wang, Yaoqi; Ning, Qiaoqing; Zhang, Yong; Gong, Chunzhi; Zhao, Wenxiang; Jing, Guangjian; Wang, Qianqian

    2016-06-01

    Dexmedetomidine (Dex) is a highly selective α2-adrenergic receptor agonist that is widely used for sedation in intensive care units and in clinical anesthesia. Dex has also been shown to possess anti-inflammatory benefits. However, the underlying mechanism by which Dex relieves the inflammatory reaction in the lung tissues of septic mice has not been fully elucidated. In this study, we aimed to evaluate the protective effects and possible mechanism of Dex on the sepsis-induced lung inflammatory response in mice. Sepsis was induced in mice models through the intraperitoneal injection of lipopolysaccharide (LPS). The preemptive administration of Dex substantially abated sepsis-induced pulmonary edema, pulmonary histopathological changes, and NF-κB p65 activity. The production of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) at both the mRNA and protein levels was also reduced. Moreover, these effects were significantly blocked by the α7 nicotinic acetylcholine receptor (α7nAChR) antagonist α-bungarotoxin (α-Bgt). α-Bgt aggravated pulmonary edema and pulmonary histopathological changes, as well as increased NF-κB p65 activity and TNF-α and IL-6 expression at both the mRNA and protein levels. The overall results demonstrate that Dex inhibits the LPS-induced inflammatory reaction in the lung tissues of septic mice partly through the α7nAChR-dependent cholinergic anti-inflammatory pathway. PMID:27074053

  1. Negative emotions boost user activity at BBC forum

    Science.gov (United States)

    Chmiel, Anna; Sobkowicz, Pawel; Sienkiewicz, Julian; Paltoglou, Georgios; Buckley, Kevan; Thelwall, Mike; Hołyst, Janusz A.

    2011-08-01

    We present an empirical study of user activity in online BBC discussion forums, measured by the number of posts written by individual debaters and the average sentiment of these posts. Nearly 2.5 million posts from over 18 thousand users were investigated. Scale-free distributions were observed for activity in individual discussion threads as well as for overall activity. The number of unique users in a thread normalized by the thread length decays with thread length, suggesting that thread life is sustained by mutual discussions rather than by independent comments. Automatic sentiment analysis shows that most posts contain negative emotions and the most active users in individual threads express predominantly negative sentiments. It follows that the average emotion of longer threads is more negative and that threads can be sustained by negative comments. An agent-based computer simulation model has been used to reproduce several essential characteristics of the analyzed system. The model stresses the role of discussions between users, especially emotionally laden quarrels between supporters of opposite opinions, and represents many observed statistics of the forum.

  2. Electroacupuncture at Zusanli Prevents Severe Scalds-Induced Gut Ischemia and Paralysis by Activating the Cholinergic Pathway

    Directory of Open Access Journals (Sweden)

    Huan Wang

    2015-01-01

    Full Text Available Severe burn injuries may result in gastrointestinal paralysis, and barrier dysfunction due to gut ischemia and lowered vagus excitability. In this study we investigate whether electroacupuncture (EA at Zusanli (ST36 could prevent severe scalds-induced gut ischemia, paralysis, and barrier dysfunction and whether the protective role of EA at ST36 is related to the vagus nerve. 35% burn area rats were divided into six groups: (a EAN: EA nonchannel acupoints followed by scald injury; (b EA: EA at ST36 after scald injury; (c VGX/EA: vagotomy (VGX before EA at ST36 and scald injury; (d VGX/EAN: VGX before EAN and scald injury; (e atropine/EA: applying atropine before scald injury and then EA at ST36; (f atropine/EAN: applying atropine before scald injury and then EA at nonchannel acupoints. EA at the Zusanli point significantly promoted the intestinal impelling ratio and increased the amount of mucosal blood flow after scald injury. The plasma diamine oxidase (DAO and intestinal permeability decreased significantly after scald injury in the EA group compared with others. However, EA after atropine injection or cervical vagotomy failed to improve intestinal motility and mucosa blood flow suggesting that the mechanism of EA may be related to the activation of the cholinergic nerve pathway.

  3. Excellent gas/oil potential boosts Sumatra activity

    Energy Technology Data Exchange (ETDEWEB)

    Beverly, B. Jr.

    1969-05-01

    A favorable combination of operating and economic factors is responsible for accelerating activity on the Indonesian island of Sumatra. In addition to increased offshore activity in the S. China Sea, Straits of Malacca and Indian Ocean, interest in onshore areas on the E. side of Sumatra (as shown by a base map) is almost unprecedented. The reasons for this interest include the following: (1) an elongated 91,000 sq mile sedimentary basin with numerous structures and proven reserves runs the entire length of Sumatra, and extends off shore; (2) paraffin-base crude normally found is of excellent quality-medium to high gravity with low sulfur content; (3) good production occurs at shallow depths to (5,000 ft) and drilling problems are not serious; (4) new production-sharing agreements between the government and operators make reworking of abandoned, older fields and secondary recovery programs highly attractive; (5) prospects are excellent for farmouts from the government oil company PN Pertambangan Minjak Nacional (Pertamina); (6) Indonesian politics are stable, government agreements with companies are fair, and security guarantees are provided operators; and (7) proximity of oil-hungary Japan virtually assures an excellent market.

  4. Support nanostructure boosts oxygen transfer to catalytically active platinum nanoparticles

    Science.gov (United States)

    Vayssilov, Georgi N.; Lykhach, Yaroslava; Migani, Annapaola; Staudt, Thorsten; Petrova, Galina P.; Tsud, Nataliya; Skála, Tomáš; Bruix, Albert; Illas, Francesc; Prince, Kevin C.; MatolíN, VladimíR.; Neyman, Konstantin M.; Libuda, Jörg

    2011-04-01

    Interactions of metal particles with oxide supports can radically enhance the performance of supported catalysts. At the microscopic level, the details of such metal-oxide interactions usually remain obscure. This study identifies two types of oxidative metal-oxide interaction on well-defined models of technologically important Pt-ceria catalysts: (1) electron transfer from the Pt nanoparticle to the support, and (2) oxygen transfer from ceria to Pt. The electron transfer is favourable on ceria supports, irrespective of their morphology. Remarkably, the oxygen transfer is shown to require the presence of nanostructured ceria in close contact with Pt and, thus, is inherently a nanoscale effect. Our findings enable us to detail the formation mechanism of the catalytically indispensable Pt-O species on ceria and to elucidate the extraordinary structure-activity dependence of ceria-based catalysts in general.

  5. Brain cholinergic impairment in liver failure

    OpenAIRE

    García Ayllón, María Salud; Cauli, Omar; Silveyra, María Ximena; Rodrigo, Regina; Candela, Asunción; Compañ, Antonio; Jover, Rodrigo; Pérez-Mateo, Miguel; Martínez, Salvador; Felipo, Vicente; Sáez-Valero, Javier

    2008-01-01

    The cholinergic system is involved in specific behavioural responses and cognitive processes. Here, we examined potential alterations in the brain levels of key cholinergic enzymes in cirrhotic patients and animal models with liver failure. An increase (∼30%) in the activity of the acetylcholine-hydrolyzing enzyme, acetylcholinesterase (AChE) is observed in the brain cortex from patients deceased from hepatic coma, while the activity of the acetylcholine-synthesizing enzyme, choline acetyltra...

  6. Efficient Power Conversion in Common Active Clamp for Interleaved Dc-Dc Boost

    Directory of Open Access Journals (Sweden)

    V. Rathinavel Subramaniam

    2014-10-01

    Full Text Available This project presents a high-efficiency and high-step-up non isolated interleaved dc to dc converter with a common active-clamp circuit. In the presented converter, the coupled-inductor boost converters are interleaved. A boost converter is used to clamp the voltage stresses of all the switches in the interleaved converters, caused by the leakage inductances present in the practical coupled inductors, to a low voltage level. The leakage energies of the inter-leaved converters are collected in a clamp capacitor and recycled to the output by the clamp boost converter. The proposed converter achieves high efficiency because of the recycling of the leakage energies, reduction of the switch voltage stress, mitigation of the output diode is reverse recovery problem, and interleaving of the converters. In many applications, high-efficiency, high-voltage step-up dc–dc converters are required as an interface between the available low voltage sources and the output loads, which are operated at much higher voltages. Examples of such applications are as follows. Different distributed energy storage components such as batteries, fuel cells, and ultra capacitors are used in the power trains of hybrid electric vehicles (HEV, electric vehicles (EV, and fuel cell vehicles (FCV. In the present power train architectures of these vehicles, the voltage levels of the energy storage elements are usually low; whereas the motors of the vehicles are driven at much higher voltages. The telecom and the computer industry utilize the standard batteries, with low voltage levels, as a back-up power source. The dc–dc converter, used in this case, is required to boost the low-input voltage of the batteries to the high voltage of the dc bus. Another example is the automotive headlamps, using the high-intensity discharge lamp ballasts..

  7. c-fos expression in brainstem premotor interneurons during cholinergically induced active sleep in the cat.

    Science.gov (United States)

    Morales, F R; Sampogna, S; Yamuy, J; Chase, M H

    1999-11-01

    The present study was undertaken to identify trigeminal premotor interneurons that become activated during carbachol-induced active sleep (c-AS). Their identification is a critical step in determining the neural circuits responsible for the atonia of active sleep. Accordingly, the retrograde tracer cholera toxin subunit B (CTb) was injected into the trigeminal motor nuclei complex to label trigeminal interneurons. To identify retrograde-labeled activated neurons, immunocytochemical techniques, designed to label the Fos protein, were used. Double-labeled (i.e., CTb(+), Fos(+)) neurons were found exclusively in the ventral portion of the medullary reticular formation, medial to the facial motor nucleus and lateral to the inferior olive. This region, which encompasses the ventral portion of the nucleus reticularis gigantocellularis and the nucleus magnocellularis, corresponds to the rostral portion of the classic inhibitory region of. This region contained a mean of 606 +/- 41.5 ipsilateral and 90 +/- 32.0 contralateral, CTb-labeled neurons. These cells were of medium-size with an average soma diameter of 20-35 micrometer. Approximately 55% of the retrogradely labeled cells expressed c-fos during a prolonged episode of c-AS. We propose that these neurons are the interneurons responsible for the nonreciprocal postsynaptic inhibition of trigeminal motoneurons that occurs during active sleep. PMID:10531453

  8. Cholinergic Mechanisms in Spinal Locomotion - Potential Target for Rehabilitation Approaches

    Directory of Open Access Journals (Sweden)

    L M Jordan

    2014-11-01

    Full Text Available Previous experiments implicate cholinergic brainstem and spinal systems in the control of locomotion. Our results demonstrate that the endogenous cholinergic propriospinal system, acting via M2 and M3 muscarinic receptors, is capable of consistently producing well-coordinated locomotor activity in the in vitro neonatal preparation, placing it in a position to contribute to normal locomotion and to provide a basis for recovery of locomotor capability in the absence of descending pathways. Tests of these suggestions, however, reveal that the spinal cholinergic system plays little if any role in the induction of locomotion, because MLR-evoked locomotion in decerebrate cats is not prevented by cholinergic antagonists. Furthermore, it is not required for the development of stepping movements after spinal cord injury, because cholinergic agonists do not facilitate the appearance of locomotion after spinal cord injury, unlike the dramatic locomotion-promoting effects of clonidine, a noradrenergic α-2 agonist. Furthermore, cholinergic antagonists actually improve locomotor activity after spinal cord injury, suggesting that plastic changes in the spinal cholinergic system interfere with locomotion rather than facilitating it. Changes that have been observed in the cholinergic innervation of motoneurons after spinal cord injury do not decrease motoneuron excitability, as expected. Instead, the development of a hyper-cholinergic state after spinal cord injury appears to enhance motoneuron output and suppress locomotion. A cholinergic suppression of afferent input from the limb after spinal cord injury is also evident from our data, and this may contribute to the ability of cholinergic antagonists to improve locomotion. Not only is a role for the spinal cholinergic system in supressing locomotion after SCI suggested by our results, but an obligatory contribution of a brainstem cholinergic relay to reticulospinal locomotor command systems is not confirmed

  9. Activity-Dependent Regulation of Substance P Expression and Topographic Map Maintenance by a Cholinergic Pathway

    OpenAIRE

    Tu, Shichun; Christopher M. Butt; Pauly, James R.; Debski, Elizabeth A.

    2000-01-01

    We have assessed the role of activity in the adult frog visual system in modulating two aspects of neuronal plasticity: neurotransmitter expression and topographic map maintenance. Chronic treatment of one tectal lobe with the non-NMDA receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione decreased the percentage of substance P-like immunoreactive (SP-IR) tectal cells in the untreated lobe while disrupting topographic map formation in the treated one. Treatment with the NMDA receptor anta...

  10. Striatal cholinergic neurotransmission requires VGLUT3.

    Science.gov (United States)

    Nelson, Alexandra B; Bussert, Timothy G; Kreitzer, Anatol C; Seal, Rebecca P

    2014-06-25

    It is now clear that many neuronal populations release more than one classical neurotransmitter, yet in most cases the functional role of corelease is unknown. Striatal cholinergic interneurons release both glutamate and acetylcholine, and vesicular loading of glutamate has been shown to enhance acetylcholine content. Using a combination of optogenetics and whole-cell recordings in mice, we now provide physiological evidence that optogenetic stimulation of cholinergic interneurons triggers monosynaptic glutamate- and acetylcholine-mediated currents in striatal fast-spiking interneurons (FSIs), both of which depend on the expression of the vesicular glutamate transporter 3 (VGLUT3). In contrast to corticostriatal glutamatergic inputs onto FSIs, which are mediated primarily by AMPA-type glutamate receptors, glutamate release by cholinergic interneurons activates both AMPA- and NMDA-type glutamate receptors, suggesting a unique role for these inputs in the modulation of FSI activity. Importantly, we find that the loss of VGLUT3 not only markedly attenuates glutamatergic and cholinergic inputs on FSIs, but also significantly decreases disynaptic GABAergic input onto medium spiny neurons (MSNs), the major output neurons of the striatum. Our data demonstrate that VGLUT3 is required for normal cholinergic signaling onto FSIs, as well as for acetylcholine-dependent disynaptic inhibition of MSNs. Thus, by supporting fast glutamatergic transmission as well as by modulating the strength of cholinergic signaling, VGLUT3 has the capacity to exert widespread influence on the striatal network. PMID:24966377

  11. Activation of nicotinic cholinergic receptors prevents ventilator-induced lung injury in rats.

    Directory of Open Access Journals (Sweden)

    Fabienne Brégeon

    Full Text Available Respiratory distress syndrome is responsible for 40 to 60 percent mortality. An over mortality of about 10 percent could result from additional lung injury and inflammation due to the life-support mechanical ventilation, which stretches the lung. It has been recently demonstrated, in vitro, that pharmacological activation of the alpha 7 nicotinic receptors (α7-nAChR could down regulate intracellular mediators involved in lung cell inflammatory response to stretch. Our aim was to test in vivo the protective effect of the pharmacological activation of the α7-nAChR against ventilator-induced lung injury (VILI. Anesthetized rats were ventilated for two hours with a high stretch ventilation mode delivering a stroke volume large enough to generate 25-cmH(2O airway pressure, and randomly assigned to four groups: pretreated with parenteral injection of saline or specific agonist of the α7-nAChR (PNU-282987, or submitted to bilateral vagus nerve electrostimulation while pre-treated or not with the α7-nAChR antagonist methyllycaconitine (MLA. Controls ventilated with a conventional stroke volume of 10 mL/kg gave reference data. Physiological indices (compliance of the respiratory system, lung weight, blood oxygenation, arterial blood pressure and lung contents of inflammatory mediators (IL-6 measured by ELISA, substance P assessed using HPLC were severely impaired after two hours of high stretch ventilation (sham group. Vagal stimulation was able to maintain the respiratory parameters close to those obtained in Controls and reduced lung inflammation except when associated to nicotinic receptor blockade (MLA, suggesting the involvement of α7-nAChR in vagally-mediated protection against VILI. Pharmacological pre-treatment with PNU-282987 strongly decreased lung injury and lung IL-6 and substance P contents, and nearly abolished the increase in plasmatic IL-6 levels. Pathological examination of the lungs confirmed the physiological differences observed

  12. Cholinergic muscarinic receptor activation augments murine intestinal epithelial cell proliferation and tumorigenesis

    International Nuclear Information System (INIS)

    Previously, we showed that M3 muscarinic receptor (M3R; gene name Chrm3) deficiency attenuates murine intestinal neoplasia, supporting the hypothesis that muscarinic receptors play an important role in intestinal tumorigenesis. To test this hypothesis, in the present study we treated mice with bethanechol, a non-selective muscarinic receptor agonist without nicotinic receptor activity, and examined its effects on azoxymethane (AOM)-induced colon neoplasia. Mice were provided with drinking water containing 400 μg/mL bethanechol chloride or water without additions (control) for a total of 20 weeks, a period that included the initial 6 weeks when mice received intraperitoneal injections of AOM. When euthanized at week 20, control mice had 8.0 ± 1.3 tumors per animal, whereas bethanechol-treated mice had 10.4 ± 1.5 tumors per mouse (mean ± SE; P = 0.023), a 30% increase. Strikingly, tumor volume per animal was increased 52% in bethanechol-treated compared with control mice (179.7 ± 21.0 vs. 111. 8 ± 22.4 mm3; P = 0.047). On histological examination, bethenechol-treated mice also had more adenocarcinomas per animal (8.0 ± 1.0 vs. 4.1 ± 0.6 for control mice, P = 0.0042). Cell proliferation in both normal mucosa and adenocarcinomas was increased in bethanechol-treated compared to control mice. Also, in tumors, bethanechol treatment increased expression of Chrm3, Egfr and post-Egfr signaling molecules Myc and cyclin D1. Bethanechol treatment increased the thickness of normal colonic mucosa and the expression of selected matrix metalloproteinase (Mmp) genes, including Mmp7, Mmp10 and Mmp13. These findings support a prominent role for muscarinic receptors in colon neoplasia, and identify post-receptor signaling molecules as potential therapeutic targets

  13. VPAC1 receptors regulate intestinal secretion and muscle contractility by activating cholinergic neurons in guinea pig jejunum.

    Science.gov (United States)

    Fung, Candice; Unterweger, Petra; Parry, Laura J; Bornstein, Joel C; Foong, Jaime P P

    2014-05-01

    In the gastrointestinal tract, vasoactive intestinal peptide (VIP) is found exclusively within neurons. VIP regulates intestinal motility via neurally mediated and direct actions on smooth muscle and secretion by a direct mucosal action, and via actions on submucosal neurons. VIP acts via VPAC1 and VPAC2 receptors; however, the subtype involved in its neural actions is unclear. The neural roles of VIP and VPAC1 receptors (VPAC1R) were investigated in intestinal motility and secretion in guinea pig jejunum. Expression of VIP receptors across the jejunal layers was examined using RT-PCR. Submucosal and myenteric neurons expressing VIP receptor subtype VPAC1 and/or various neurochemical markers were identified immunohistochemically. Isotonic muscle contraction was measured in longitudinal muscle-myenteric plexus preparations. Electrogenic secretion across mucosa-submucosa preparations was measured in Ussing chambers by monitoring short-circuit current. Calretinin(+) excitatory longitudinal muscle motor neurons expressed VPAC1R. Most cholinergic submucosal neurons, notably NPY(+) secretomotor neurons, expressed VPAC1R. VIP (100 nM) induced longitudinal muscle contraction that was inhibited by TTX (1 μM), PG97-269 (VPAC1 antagonist; 1 μM), and hyoscine (10 μM), but not by hexamethonium (200 μM). VIP (50 nM)-evoked secretion was depressed by hyoscine or PG97-269 and involved a small TTX-sensitive component. PG97-269 and TTX combined did not further depress the VIP response observed in the presence of PG97-269 alone. We conclude that VIP stimulates ACh-mediated longitudinal muscle contraction via VPAC1R on cholinergic motor neurons. VIP induces Cl(-) secretion directly via epithelial VPAC1R and indirectly via VPAC1R on cholinergic secretomotor neurons. No evidence was obtained for involvement of other neural VIP receptors. PMID:24578344

  14. Multiple cholinergic differentiation factors are present in footpad extracts: comparison with known cholinergic factors

    OpenAIRE

    Rao, M S; Patterson, Paul H.; Landis, S C

    1992-01-01

    Sweat glands in rat footpads contain a neuronal differentiation activity that switches the phenotype of sympathetic neurons from noradrenergic to cholinergic during normal development in vivo. Extracts of developing and adult sweat glands induce changes in neurotransmitter properties in cultured sympathetic neurons that mimic those observed in vivo. We have characterized further the factors present in the extract and compared their properties to those of known cholinergic factors. When assaye...

  15. Regulated Extracellular Choline Acetyltransferase Activity- The Plausible Missing Link of the Distant Action of Acetylcholine in the Cholinergic Anti-Inflammatory Pathway.

    Directory of Open Access Journals (Sweden)

    Swetha Vijayaraghavan

    Full Text Available Acetylcholine (ACh, the classical neurotransmitter, also affects a variety of nonexcitable cells, such as endothelia, microglia, astrocytes and lymphocytes in both the nervous system and secondary lymphoid organs. Most of these cells are very distant from cholinergic synapses. The action of ACh on these distant cells is unlikely to occur through diffusion, given that ACh is very short-lived in the presence of acetylcholinesterase (AChE and butyrylcholinesterase (BuChE, two extremely efficient ACh-degrading enzymes abundantly present in extracellular fluids. In this study, we show compelling evidence for presence of a high concentration and activity of the ACh-synthesizing enzyme, choline-acetyltransferase (ChAT in human cerebrospinal fluid (CSF and plasma. We show that ChAT levels are physiologically balanced to the levels of its counteracting enzymes, AChE and BuChE in the human plasma and CSF. Equilibrium analyses show that soluble ChAT maintains a steady-state ACh level in the presence of physiological levels of fully active ACh-degrading enzymes. We show that ChAT is secreted by cultured human-brain astrocytes, and that activated spleen lymphocytes release ChAT itself rather than ACh. We further report differential CSF levels of ChAT in relation to Alzheimer's disease risk genotypes, as well as in patients with multiple sclerosis, a chronic neuroinflammatory disease, compared to controls. Interestingly, soluble CSF ChAT levels show strong correlation with soluble complement factor levels, supporting a role in inflammatory regulation. This study provides a plausible explanation for the long-distance action of ACh through continuous renewal of ACh in extracellular fluids by the soluble ChAT and thereby maintenance of steady-state equilibrium between hydrolysis and synthesis of this ubiquitous cholinergic signal substance in the brain and peripheral compartments. These findings may have important implications for the role of cholinergic

  16. Chronic Treatment with Squid Phosphatidylserine Activates Glucose Uptake and Ameliorates TMT-Induced Cognitive Deficit in Rats via Activation of Cholinergic Systems

    Directory of Open Access Journals (Sweden)

    Hyun-Jung Park

    2012-01-01

    Full Text Available The present study examined the effects of squid phosphatidylserine (Squid-PS on the learning and memory function and the neural activity in rats with TMT-induced memory deficits. The rats were administered saline or squid derived Squid-PS (Squid-PS 50 mg kg−1, p.o. daily for 21 days. The cognitive improving efficacy of Squid-PS on the amnesic rats, which was induced by TMT, was investigated by assessing the passive avoidance task and by performing choline acetyltransferase (ChAT and acetylcholinesterase (AchE immunohistochemistry. 18F-Fluorodeoxyglucose and performed a positron emission tomography (PET scan was also performed. In the passive avoidance test, the control group which were injected with TMT showed a markedly lower latency time than the non-treated normal group (P<0.05. However, treatment of Squid-PS significantly recovered the impairment of memory compared to the control group (P<0.05. Consistent with the behavioral data, Squid-PS significantly alleviated the loss of ChAT immunoreactive neurons in the hippocampal CA3 compared to that of the control group (P<0.01. Also, Squid-PS significantly increased the AchE positive neurons in the hippocampal CA1 and CA3. In the PET analysis, Squid-PS treatment increased the glucose uptake more than twofold in the frontal lobe and the hippocampus (P<0.05, resp.. These results suggest that Squid-PS may be useful for improving the cognitive function via regulation of cholinergic enzyme activity and neural activity.

  17. Cholinergic dysfunction in Parkinson's disease.

    Science.gov (United States)

    Müller, Martijn L T M; Bohnen, Nicolaas I

    2013-09-01

    There is increasing interest in the clinical effects of cholinergic basal forebrain and tegmental pedunculopontine complex (PPN) projection degeneration in Parkinson's disease (PD). Recent evidence supports an expanded role beyond cognitive impairment, including effects on olfaction, mood, REM sleep behavior disorder, and motor functions. Cholinergic denervation is variable in PD without dementia and may contribute to clinical symptom heterogeneity. Early in vivo imaging evidence that impaired cholinergic integrity of the PPN associates with frequent falling in PD is now confirmed by human post-mortem evidence. Brainstem cholinergic lesioning studies in primates confirm the role of the PPN in mobility impairment. Degeneration of basal forebrain cholinergic projections correlates with decreased walking speed. Cumulatively, these findings provide evidence for a new paradigm to explain dopamine-resistant features of mobility impairments in PD. Recognition of the increased clinical role of cholinergic system degeneration may motivate new research to expand indications for cholinergic therapy in PD. PMID:23943367

  18. Nitrergic ventro-medial medullary neurons activated during cholinergically induced active (rapid eye movement) sleep in the cat.

    Science.gov (United States)

    Pose, I; Sampogna, S; Chase, M H; Morales, F R

    2011-01-13

    The rostral ventro-medial medullary reticular formation is a complex structure that is involved with a variety of motor functions. It contains glycinergic neurons that are activated during active (rapid eye movement (REM)) sleep (AS); these neurons appear to be responsible for the postsynaptic inhibition of motoneurons that occurs during this state. We have reported that neurons in this same region contain nitric oxide (NO) synthase and that they innervate brainstem motor pools. In the present study we examined the c-fos expression of these neurons after carbachol-induced active sleep (C-AS). Three control and four experimental cats were employed to identify c-fos expressing nitrergic neurons using immunocytochemical techniques to detect the Fos protein together with neuronal nitric oxide synthase (nNOS) or nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase activity. The classical neurotransmitter content of the nitrergic cells in this region was examined through the combination of immunocytochemical techniques for the detection of glutamate, glycine, choline acetyltransferase (ChAT), tyrosine hydroxilase (TH) or GABA together with nNOS. During C-AS, there was a 1074% increase in the number of nitrergic neurons that expressed c-fos. These neurons did not contain glycine, ChAT, TH or GABA, but a subpopulation (15%) of them displayed glutamate-like immunoreactivity. Therefore, some of these neurons contain both an excitatory neurotransmitter (glutamate) and an excitatory neuromodulator (NO); the neurotransmitter content of the rest of them remains to be determined. Because some of the nitrergic neurons innervate brainstem motoneurons it is possible that they participate in the generation of tonic and excitatory phasic motor events that occur during AS. We also suggest that these nitrergic neurons may be involved in autonomic regulation during this state. In addition, because NO has trophic effects on target neurons, the present findings represent the

  19. TIMING IS EVERYTHING, EVEN FOR CHOLINERGIC CONTROL

    OpenAIRE

    Berg, Darwin K.

    2011-01-01

    Synaptic plasticity is widely considered to be a cellular mechanism underlying learning and memory. In this issue of Neuron, Gu and Yakel show that the precise timing of a single cholinergic pulse of activity can determine whether plasticity will occur at a glutamatergic synapse and confer long-term potentiation versus depression.

  20. Analysis of Parallel Topology for Active Power Factor Correction Using Single and Dual Mode Boost Converters

    Directory of Open Access Journals (Sweden)

    Md. Mosfiqur Rahaman

    2014-11-01

    Full Text Available The ratio between real or average power and apparent power known as power factor has a high impact on power system industries. Efficient usage of the real power is very indicative in developing a power system. With the profusely development of technology in power semiconductor devices, the rate of using power electronic systems has expanded to new and wide application range that include residential, commercial, aerospace and other systems. In the nonlinear system, loads are the main source of harmonics. So that nonlinear behavior puts a question mark on their high efficiency. The current drawn by power electronic interfaces from the line is distorted resulting in a high total Harmonic Distortion and low p.f. this creates adverse effects on the power system include increased magnitudes of neutral currents in three phase systems, overheating in transformers and induction motors. This paper aims to develop a circuit for PFC by using active filtering approach by implementing two (single & dual boost converters arranged in parallel, for improving circuit quality and switching loss. This work actually involves simulation of basic power electronic circuit and it starts with simple circuit with a gradual increase in complexity by inclusion of new components and their subsequent effect on current and voltage wave forms. We focused to improve the condition of input current waveforms for making it sinusoidal by tuning the circuits.

  1. Nematode cholinergic pharmacology

    International Nuclear Information System (INIS)

    Nematode acetylcholine (ACh) receptors were characterized using both biochemical and electrophysiological techniques, including: (1) receptor binding studies in crude homogenates of the free-living nematode Caenorhabditis elegans and the parasitic nematode Ascaris lumbricoides with the high-affinity probe [3H]N-methylscopolamine ([3H]NMS) which binds to muscarinic receptors in many vertebrate and invertebrate tissues (2) measurement of depolarization and contraction induced by a variety of cholinergic agents, including N-methylscopolamine (NMS), in an innervated dorsal muscle strip preparation of Ascaris; (3) examination of the antagonistic actions of d-tubocurarine (dTC) and NMS at dorsal neuromuscular junction; (4) measurement of input resistance changes in Ascaris commissural motorneurons induced by ACh, dTC, NMS, pilocarpine and other cholinergic drugs

  2. Nematode cholinergic pharmacology

    Energy Technology Data Exchange (ETDEWEB)

    Segerberg, M.A.

    1989-01-01

    Nematode acetylcholine (ACh) receptors were characterized using both biochemical and electrophysiological techniques, including: (1) receptor binding studies in crude homogenates of the free-living nematode Caenorhabditis elegans and the parasitic nematode Ascaris lumbricoides with the high-affinity probe ({sup 3}H)N-methylscopolamine (({sup 3}H)NMS) which binds to muscarinic receptors in many vertebrate and invertebrate tissues (2) measurement of depolarization and contraction induced by a variety of cholinergic agents, including N-methylscopolamine (NMS), in an innervated dorsal muscle strip preparation of Ascaris; (3) examination of the antagonistic actions of d-tubocurarine (dTC) and NMS at dorsal neuromuscular junction; (4) measurement of input resistance changes in Ascaris commissural motorneurons induced by ACh, dTC, NMS, pilocarpine and other cholinergic drugs.

  3. Chitosan boosts the antimicrobial activity of Origanum vulgare essential oil in modified atmosphere packaged pork.

    Science.gov (United States)

    Paparella, Antonello; Mazzarrino, Giovanni; Chaves-López, Clemencia; Rossi, Chiara; Sacchetti, Giampiero; Guerrieri, Oana; Serio, Annalisa

    2016-10-01

    The potential of chitosan as a possible booster of the antimicrobial activity of Origanum vulgare EO (OEO) against spoilage bacteria and Listeria monocytogenes was investigated in fresh pork meat. Pork fillets were inoculated with 3 L. monocytogenes strains, dipped either in Origanum vulgare (oregano) Essential Oil (OEO) at 2 and 4%, or in chitosan 1% alone or added with 2 and 4% OEO, then packed under modified atmosphere (70% O2, 20% CO2, 10% N2) and stored at 4 °C for 15 days. OEO did not reduce L. monocytogenes growth, while 2 Log decrease was obtained after 2 days of storage in treatments with chitosan alone or with OEO, with growth inhibition up to day 15 in samples with chitosan and OEO 4%. When OEO was combined with chitosan, total viable counts and spoilage bacteria were reduced and contained over time, particularly Pseudomonas (2.0 Log CFU/g at day 15) and Brochothrix thermosphacta (undetectable). All the treatments applied extended meat shelf-life with respect to control, whose commercial shelf-life was 10 days. Chitosan treatments enhanced L* and maintained a* values almost stable during storage. Chitosan and OEO singly applied reduced lipid oxidation (0.62-0.75 mg malondialdehyde/Kg meat) compared to control (0.99 mg malondialdehyde/Kg meat). Finally, chitosan treated samples were not recognized with respect to the control, whereas OEO gave bitter taste; chitosan with OEO instead mitigated the effect of OEO addition to meat. Chitosan combined with OEO boosts its antimicrobial activity and shows a potential for application in industrial production of fresh pork in MAP, to achieve shelf-life extension, control of L. monocytogenes growth, stability of color and protective effect from oxidation, with low sensory impact. PMID:27375241

  4. Cholinergic Circuit Control of Postnatal Neurogenesis

    Science.gov (United States)

    Asrican, Brent; Paez-Gonzalez, Patricia; Erb, Joshua; Kuo, Chay T.

    2016-01-01

    New neuron addition via continued neurogenesis in the postnatal/adult mammalian brain presents a distinct form of nervous system plasticity. During embryonic development, precise temporal and spatial patterns of neurogenesis are necessary to create the nervous system architecture. Similar between embryonic and postnatal stages, neurogenic proliferation is regulated by neural stem cell (NSC)-intrinsic mechanisms layered upon cues from their local microenvironmental niche. Following developmental assembly, it remains relatively unclear what may be the key driving forces that sustain continued production of neurons in the postnatal/adult brain. Recent experimental evidence suggests that patterned activity from specific neural circuits can also directly govern postnatal/adult neurogenesis. Here, we review experimental findings that revealed cholinergic modulation, and how patterns of neuronal activity and acetylcholine release may differentially or synergistically activate downstream signaling in NSCs. Higher-order excitatory and inhibitory inputs regulating cholinergic neuron firing, and their implications in neurogenesis control are also considered.

  5. Cholinergic Mechanisms in Spinal Locomotion - Potential Target for Rehabilitation Approaches

    OpenAIRE

    Jordan, L M; Noga, B. R.; Cabaj, A. M.; J Provencher

    2014-01-01

    Previous experiments implicate cholinergic brainstem and spinal systems in the control of locomotion. Our results demonstrate that the endogenous cholinergic propriospinal system, acting via M2 and M3 muscarinic receptors, is capable of consistently producing well-coordinated locomotor activity in the in vitro neonatal preparation, placing it in a position to contribute to normal locomotion and to provide a basis for recovery of locomotor capability in the absence of descending pathways. Test...

  6. Effect of Ginger and Turmeric Rhizomes on Inflammatory Cytokines Levels and Enzyme Activities of Cholinergic and Purinergic Systems in Hypertensive Rats.

    Science.gov (United States)

    Akinyemi, Ayodele Jacob; Thomé, Gustavo Roberto; Morsch, Vera Maria; Bottari, Nathieli B; Baldissarelli, Jucimara; de Oliveira, Lizielle Souza; Goularte, Jeferson Ferraz; Belló-Klein, Adriane; Duarte, Thiago; Duarte, Marta; Boligon, Aline Augusti; Athayde, Margareth Linde; Akindahunsi, Akintunde Afolabi; Oboh, Ganiyu; Schetinger, Maria Rosa Chitolina

    2016-05-01

    Inflammation exerts a crucial pathogenic role in the development of hypertension. Hence, the aim of the present study was to investigate the effects of ginger (Zingiber officinale) and turmeric (Curcuma longa) on enzyme activities of purinergic and cholinergic systems as well as inflammatory cytokine levels in Nω-nitro-L-arginine methyl ester hydrochloride-induced hypertensive rats. The rats were divided into seven groups (n = 10); groups 1-3 included normotensive control rats, hypertensive (Nω-nitro-L-arginine methyl ester hydrochloride) rats, and hypertensive control rats treated with atenolol (an antihypertensive drug), while groups 4 and 5 included normotensive and hypertensive (Nω-nitro-L-arginine methyl ester hydrochloride) rats treated with 4 % supplementation of turmeric, respectively, and groups 6 and 7 included normotensive and hypertensive rats treated with 4 % supplementation of ginger, respectively. The animals were induced with hypertension by oral administration of Nω-nitro-L-arginine methyl ester hydrochloride, 40 mg/kg body weight. The results revealed a significant increase in ATP and ADP hydrolysis, adenosine deaminase, and acetylcholinesterase activities in lymphocytes from Nω-nitro-L-arginine methyl ester hydrochloride hypertensive rats when compared with the control rats. In addition, an increase in serum butyrylcholinesterase activity and proinflammatory cytokines (interleukin-1 and - 6, interferon-γ, and tumor necrosis factor-α) with a concomitant decrease in anti-inflammatory cytokines (interleukin-10) was observed in Nω-nitro-L-arginine methyl ester hydrochloride hypertensive rats. However, dietary supplementation of both rhizomes was efficient in preventing these alterations in hypertensive rats by decreasing ATP hydrolysis, acetylcholinesterase, and butyrylcholinesterase activities and proinflammatory cytokines in hypertensive rats. Thus, these activities could suggest a possible insight about the protective

  7. TASK Channels on Basal Forebrain Cholinergic Neurons Modulate Electrocortical Signatures of Arousal by Histamine

    OpenAIRE

    Vu, Michael T.; Du, Guizhi; Bayliss, Douglas A.; Horner, Richard L.

    2015-01-01

    Basal forebrain cholinergic neurons are the main source of cortical acetylcholine, and their activation by histamine elicits cortical arousal. TWIK-like acid-sensitive K+ (TASK) channels modulate neuronal excitability and are expressed on basal forebrain cholinergic neurons, but the role of TASK channels in the histamine-basal forebrain cholinergic arousal circuit is unknown. We first expressed TASK channel subunits and histamine Type 1 receptors in HEK cells. Application of histamine in vitr...

  8. Buck-boost converter for simultaneous semi-active vibration control and energy harvesting for electromagnetic regenerative shock absorber

    Science.gov (United States)

    Li, Peng; Zhang, Chongxiao; Kim, Junyoung; Yu, Liangyao; Zuo, Lei

    2014-04-01

    Regenerative semi-active suspensions can capture the previously dissipated vibration energy and convert it to usable electrical energy for powering on-board electronic devices, while achieve both the better ride comfort and improved road handling performance at the same time when certain control is applied. To achieve this objective, the power electronics interface circuit connecting the energy harvester and the electrical loads, which can perform simultaneous vibration control and energy harvesting function is in need. This paper utilized a buck-boost converter for simultaneous semi-active vibration control and energy harvesting with electromagnetic regenerative shock absorber, which utilizes a rotational generator to converter the vibration energy to electricity. It has been found that when the circuit works in discontinuous current mode (DCM), the ratio between the input voltage and current is only related to the duty cycle of the switch pulse width modulation signal. Using this property, the buck-boost converter can be used to perform semi-active vibration control by controlling the load connected between the terminals of the generator in the electromagnetic shock absorber. While performing the vibration control, the circuit always draw current from the shock absorber and the suspension remain dissipative, and the shock absorber takes no additional energy to perform the vibration control. The working principle and dynamics of the circuit has been analyzed and simulations were performed to validate the concept.

  9. Brain cholinergic impairment in liver failure.

    Science.gov (United States)

    García-Ayllón, María-Salud; Cauli, Omar; Silveyra, María-Ximena; Rodrigo, Regina; Candela, Asunción; Compañ, Antonio; Jover, Rodrigo; Pérez-Mateo, Miguel; Martínez, Salvador; Felipo, Vicente; Sáez-Valero, Javier

    2008-11-01

    The cholinergic system is involved in specific behavioural responses and cognitive processes. Here, we examined potential alterations in the brain levels of key cholinergic enzymes in cirrhotic patients and animal models with liver failure. An increase (~30%) in the activity of the acetylcholine-hydrolyzing enzyme, acetylcholinesterase (AChE) is observed in the brain cortex from patients deceased from hepatic coma, while the activity of the acetylcholine-synthesizing enzyme, choline acetyltransferase, remains unaffected. In agreement with the human data, AChE activity in brain cortical extracts of bile duct ligated (BDL) rats was increased (~20%) compared to controls. A hyperammonemic diet did not result in any further increase of AChE levels in the BDL model, and no change was observed in hyperammonemic diet rats without liver disease. Portacaval shunted rats which display increased levels of cerebral ammonia did not show any brain cholinergic abnormalities, confirming that high ammonia levels do not play a role in brain AChE changes. A selective increase of tetrameric AChE, the major AChE species involved in hydrolysis of acetylcholine in the brain, was detected in both cirrhotic humans and BDL rats. Histological examination of BDL and non-ligated rat brains shows that the subcellular localization of both AChE and choline acetyltransferase, and thus the accessibility to their substrates, appears unaltered by the pathological condition. The BDL-induced increase in AChE activity was not parallelled by an increase in mRNA levels. Increased AChE in BDL cirrhotic rats leads to a pronounced decrease (~50-60%) in the levels of acetylcholine. Finally, we demonstrate that the AChE inhibitor rivastigmine is able to improve memory deficits in BDL rats. One week treatment with rivastigmine (0.6 mg/kg; once a day, orally, for a week) resulted in a 25% of inhibition in the enzymatic activity of AChE with no change in protein composition, as assessed by sucrose density gradient

  10. Cholinergic neurons in the dorsomedial hypothalamus regulate mouse brown adipose tissue metabolism

    Directory of Open Access Journals (Sweden)

    Jae Hoon Jeong

    2015-06-01

    Conclusion: DMH cholinergic neurons directly send efferent signals to sympathetic premotor neurons in the Rpa. Elevated cholinergic input to this area reduces BAT activity through activation of M2 mAChRs on serotonergic neurons. Therefore, the direct DMHACh–Rpa5-HT pathway may mediate physiological heat-defense responses to elevated environmental temperature.

  11. Glucocorticoid programming of the mesopontine cholinergic system

    Directory of Open Access Journals (Sweden)

    Sónia eBorges

    2013-12-01

    Full Text Available Stress perception, response, adaptation and coping strategies are individually distinct, and the sequel of stress and/or glucocorticoids is also distinct between subjects. In the last years, it has become clear that early life stress is a powerful modulator of neuroendocrine stress-responsive circuits, programming intrinsic susceptibility to stress, and potentiating the appearance of stress-related disorders such as depression, anxiety and addiction. Herein we were interested in understanding how early life experiences reset the normal processing of negative stimuli, leading to emotional dysfunction. Animals prenatally exposed to glucocorticoids (iuGC present hyperanxiety, increased fear behaviour and hyper-reactivity to negative stimuli. In parallel, we found a remarkable increase in the number of aversive 22kHz ultrasonic vocalizations in response to an aversive cue. Considering the suggested role of the mesopontine tegmentum cholinergic pathway, arising from the laterodorsal tegmental nucleus (LDT and pedunculopontine tegmental nucleus (PPT, in the initiation of 22kHz vocalizations and hypothetically in the control of emotional arousal and tone, we decided to evaluate the condition of this circuit in iuGC animals. Notably, in a basal situation, iuGC animals present increased choline acetyltransferase (ChAT expression in the LDT and PPT, but not in other cholinergic nuclei, namely in the nucleus basalis of Meynert. In addition, and in accordance with the amplified response to an adverse stimulus of iuGC animals, we found marked changes in the cholinergic activation pattern of LDT and PPT regions. Altogether, our results suggest a specific cholinergic pathway programing by prenatal GC, and hint that this may be of relevance in setting individuals stress vulnerability threshold.

  12. A capacitor-free CMOS LDO regulator with AC-boosting and active-feedback frequency compensation

    International Nuclear Information System (INIS)

    A capacitor-free CMOS low-dropout (LDO) regulator for system-on-chip (SoC) applications is presented. By adopting AC-boosting and active-feedback frequency compensation (ACB-AFFC), the proposed LDO regulator, which is independent of an off-chip capacitor, provides high closed-loop stability. Moreover, a slew rate enhancement circuit is adopted to increase the slew rate and decrease the output voltage dips when the load current is suddenly switched from low to high. The LDO regulator is designed and fabricated in a 0.6 μm CMOS process. The active silicon area is only 770 x 472 μm2. Experimental results show that the total error of the output voltage due to line variation is less than ±0.197%. The load regulation is only 0.35 mV/mA when the load current changes from 0 to 100 mA.

  13. SiC MOSFET Based Single Phase Active Boost Rectifier with Power Factor Correction for Wireless Power Transfer Applications

    Energy Technology Data Exchange (ETDEWEB)

    Onar, Omer C [ORNL; Tang, Lixin [ORNL; Chinthavali, Madhu Sudhan [ORNL; Campbell, Steven L [ORNL; Miller (JNJ), John M. [JNJ-Miller PLC

    2014-01-01

    Wireless Power Transfer (WPT) technology is a novel research area in the charging technology that bridges the utility and the automotive industries. There are various solutions that are currently being evaluated by several research teams to find the most efficient way to manage the power flow from the grid to the vehicle energy storage system. There are different control parameters that can be utilized to compensate for the change in the impedance due to variable parameters such as battery state-of-charge, coupling factor, and coil misalignment. This paper presents the implementation of an active front-end rectifier on the grid side for power factor control and voltage boost capability for load power regulation. The proposed SiC MOSFET based single phase active front end rectifier with PFC resulted in >97% efficiency at 137mm air-gap and >95% efficiency at 160mm air-gap.

  14. Cholinergic activation of the murine trachealis muscle via non-vesicular acetylcholine release involving low-affinity choline transporters.

    Science.gov (United States)

    Nassenstein, Christina; Wiegand, Silke; Lips, Katrin S; Li, Guanfeng; Klein, Jochen; Kummer, Wolfgang

    2015-11-01

    In addition to quantal, vesicular release of acetylcholine (ACh), there is also non-quantal release at the motor endplate which is insufficient to evoke postsynaptic responses unless acetylcholinesterase (AChE) is inhibited. We here addressed potential non-quantal release in the mouse trachea by organ bath experiments and (immuno)histochemical methods. Electrical field stimulation (EFS) of nerve terminals elicited tracheal constriction that is largely due to ACh release. Classical enzyme histochemistry demonstrated acetylcholinesterase (AChE) activity in nerve fibers in the muscle and butyrylcholinesterase (BChE) activity in the smooth muscle cells. Acute inhibition of both esterases by eserine significantly raised tracheal tone which was fully sensitive to atropine. This effect was reduced, but not abolished, in AChE, but not in BChE gene-deficient mice. The eserine-induced increase in tracheal tone was unaffected by vesamicol (10(-5)M), an inhibitor of the vesicular acetylcholine transporter, and by corticosterone (10(-4)M), an inhibitor of organic cation transporters. Hemicholinium-3, in low concentrations an inhibitor of the high-affinity choline transporter-1 (CHT1), completely abrogated the eserine effects when applied in high concentrations (10(-4)M) pointing towards an involvement of low-affinity choline transporters. To evaluate the cellular sources of non-quantal ACh release in the trachea, expression of low-affinity choline transporter-like family (CTL1-5) was evaluated by RT-PCR analysis. Even though these transporters were largely abundant in the epithelium, denudation of airway epithelial cells had no effect on eserine-induced tracheal contraction, indicating a non-quantal release of ACh from non-epithelial sources in the airways. These data provide evidence for an epithelium-independent non-vesicular, non-quantal ACh release in the mouse trachea involving low-affinity choline transporters. PMID:26278668

  15. Linking Cholinergic Interneurons, Synaptic Plasticity, and Behavior during the Extinction of a Cocaine-Context Association.

    Science.gov (United States)

    Lee, Junuk; Finkelstein, Joel; Choi, Jung Yoon; Witten, Ilana B

    2016-06-01

    Despite the fact that cholinergic interneurons are a key cell type within the nucleus accumbens, a relationship between synaptic plasticity and the in vivo activity of cholinergic interneurons remains to be established. Here, we identify a three-way link between the activity of cholinergic interneurons, synaptic plasticity, and learning in mice undergoing the extinction of a cocaine-context association. We found that activity of cholinergic interneurons regulates extinction learning for a cocaine-context association and generates a sustained reduction in glutamatergic presynaptic strength onto medium spiny neurons. Interestingly, activation of cholinergic interneurons does not support reinforcement learning or plasticity by itself, suggesting that these neurons have a modulatory rather than a reinforcing function. PMID:27210555

  16. Electroacupuncture at Zusanli (ST36 Prevents Intestinal Barrier and Remote Organ Dysfunction following Gut Ischemia through Activating the Cholinergic Anti-Inflammatory-Dependent Mechanism

    Directory of Open Access Journals (Sweden)

    Sen Hu

    2013-01-01

    Full Text Available This study investigated the protective effect and mechanism of electroacupuncture at ST36 points on the intestinal barrier dysfunction and remote organ injury after intestinal ischemia and reperfusion injury in rats. Rats were subjected to gut ischemia for 30 min, and then received electroacupuncture for 30 min with or without abdominal vagotomy or intraperitoneal administration of cholinergic α7 nicotinic acetylcholine receptor (α7nAChR inhibitor. Then we compared its effects with electroacupuncture at nonchannel points, vagal nerve stimulation, or intraperitoneal administration of cholinergic agonist. Cytokine levels in plasma and tissue of intestine, lung, and liver were assessed 60 min after reperfusion. Intestinal barrier injury was detected by histology, gut injury score, the permeability to 4 kDa FITC-dextran, and changes in tight junction protein ZO-1 using immunofluorescence and Western blot. Electroacupuncture significantly lowered the levels of tumor necrosis factor-α and interleukin-8 in plasma and organ tissues, decreased intestinal permeability to FITC-dextran, and prevented changes in ZO-1 protein expression and localization. However, abdominal vagotomy or intraperitoneal administration of cholinergic α7nAChR inhibitor reversed these effects of electroacupuncture. These findings suggest that electroacupuncture attenuates the systemic inflammatory response through protection of intestinal barrier integrity after intestinal ischemia injury in the presence of an intact vagus nerve.

  17. Paying attention to smell: Cholinergic signaling in the olfactory bulb.

    Directory of Open Access Journals (Sweden)

    Rinaldo David D'Souza

    2014-09-01

    Full Text Available The tractable, layered architecture of the olfactory bulb (OB, and its function as a relay between odor input and higher cortical processing, makes it an attractive model to study how sensory information is processed at a synaptic and circuit level. The OB is also the recipient of strong neuromodulatory inputs, chief among them being the central cholinergic system. Cholinergic axons from the basal forebrain modulate the activity of various cells and synapses within the OB, particularly the numerous dendrodendritic synapses, resulting in highly variable responses of OB neurons to odor input that is dependent upon the behavioral state of the animal. Behavioral, electrophysiological, anatomical, and computational studies examining the function of muscarinic and nicotinic cholinergic receptors expressed in the OB have provided valuable insights into the role of acetylcholine (ACh in regulating its function. We here review various studies examining the modulation of OB function by cholinergic fibers and their target receptors, and provide putative models describing the role that cholinergic receptor activation might play in the encoding of odor information.

  18. Cerebral cortical astroglia from the trisomy 16 mouse, a model for Down syndrome, produce neuronal cholinergic deficits in cell culture

    OpenAIRE

    Nelson, P. G.; Fitzgerald, S.; Rapoport, S I; Neale, E A; Galdzicki, Z; Dunlap, V.; Bowers, L; v. Agoston, D.

    1997-01-01

    Trisomy 21 (Down syndrome) is associated with a high incidence of Alzheimer disease and with deficits in cholinergic function in humans. We used the trisomy 16 (Ts16) mouse model for Down syndrome to identify the cellular basis for the cholinergic dysfunction. Cholinergic neurons and cerebral cortical astroglia, obtained separately from Ts16 mouse fetuses and their euploid littermates, were cultured in various combinations. Choline acetyltransferase activity and cholinergic neuron number were...

  19. Cortical cholinergic innervation: Distribution and source in monkeys

    International Nuclear Information System (INIS)

    In Alzheimer's disease (AD) and its late-life variant, senile dementia of the Alzheimer's type (SDAT), the predominant neurochemical abnormalities are marked decrements in the activities of ChAT and AChE, the high affinity uptake of tritium-choline, and synthesis of acetylcholine. Two studies are undertaken to delineate more clearly the variability of cortical cholinergic innervation and the contribution of the Ch system, particularly the Ch4, to this cholinergic innervation. In the first study, ChAT activity was assessed in multiple samples of neocortex from seven normal cynomolgus monkeys. In the second study, the nbM was lesioned in order to determine the contribution of the Ch system to cortical cholinergic innervation

  20. Model Vestibular Nuclei Neurons Can Exhibit a Boosting Nonlinearity Due to an Adaptation Current Regulated by Spike-Triggered Calcium and Calcium-Activated Potassium Channels

    Science.gov (United States)

    Schneider, Adam D.

    2016-01-01

    In vitro studies have previously found a class of vestibular nuclei neurons to exhibit a bidirectional afterhyperpolarization (AHP) in their membrane potential, due to calcium and calcium-activated potassium conductances. More recently in vivo studies of such vestibular neurons were found to exhibit a boosting nonlinearity in their input-output tuning curves. In this paper, a Hodgkin-Huxley (HH) type neuron model, originally developed to reproduce the in vitro AHP, is shown to produce a boosting nonlinearity similar to that seen in vivo for increased the calcium conductance. Indicative of a bifurcation, the HH model is reduced to a generalized integrate-and-fire (IF) model that preserves the bifurcation structure and boosting nonliearity. By then projecting the neuron model’s phase space trajectories into 2D, the underlying geometric mechanism relating the AHP and boosting nonlinearity is revealed. Further simplifications and approximations are made to derive analytic expressions for the steady steady state firing rate as a function of bias current, μ, as well as the gain (i.e. its slope) and the position of its peak at μ = μ*. Finally, although the boosting nonlinearity has not yet been experimentally observed in vitro, testable predictions indicate how it might be found. PMID:27427914

  1. Enhancement of fibroblast activation protein α-based vaccines and adenovirus boost immunity by cyclophosphamide through inhibiting IL-10 expression in 4T1 tumor bearing mice.

    Science.gov (United States)

    Xia, Qiu; Geng, Fei; Zhang, Fang-Fang; Liu, Chen-Lu; Xu, Ping; Lu, Zhen-Zhen; Zhang, Hai-Hong; Kong, Wei; Yu, Xiang-Hui

    2016-08-31

    Fibroblast activation protein α (FAPα) is expressed in cancer-associated fibroblasts (CAFs) of more than 90% of malignant epithelia carcinomas. CAFs are the main type of cells in the tumor microenvironment which offer nutrition and protection to the tumor and regulate immunosuppression. To eliminate CAFs, a vaccine targeting FAPα may be used with a heterologous prime-boost strategy to enhance the FAPα-specific cellular immunity. Here, a FAP vaccine using a recombinant adenovirus (rAd) vector was constructed as well as a DNA vaccine reported in our previous work. Although the DNA prime-rAd boost strategy enhanced FAPα-specific immune responses, improvement of anti-tumor immunity effects was not observed. Examination of immunosuppressive factors revealed that high expression of the IL-10 cytokine was considered the main cause of the failure of the prime-boost strategy. However, heterologous vaccination in combination with a low-dose of cyclophosphamide (CY), which was reported to reduce IL-10 production and promote a shift from immunosuppression to immunopotentiation, resulted in enhanced effects in terms of numbers of effector T cells and tumor growth inhibition rates, compared to the CY alone or DNA alone group. Tumor growth was inhibited markedly when the prime-boost strategy was combined with CY in both the prophylactic and therapeutic settings and the survival time of 4T1 tumor bearing mice was also prolonged significantly. With the reduction of IL-10, enhancement of the anti-tumor effect by the prime-boost strategy was observed. These results suggest that FAPα-targeted rAd boosting in combination with CY is an attractive approach to overcoming immunosuppression in cancer vaccines. PMID:27498213

  2. Axotomy-induced neurotrophic withdrawal causes the loss of phenotypic differentiation and downregulation of NGF signalling, but not death of septal cholinergic neurons

    Directory of Open Access Journals (Sweden)

    Inestrosa Nibaldo C

    2010-01-01

    Full Text Available Abstract Background Septal cholinergic neurons account for most of the cholinergic innervations of the hippocampus, playing a key role in the regulation of hippocampal synaptic activity. Disruption of the septo-hippocampal pathway by an experimental transection of the fimbria-fornix drastically reduces the target-derived trophic support received by cholinergic septal neurons, mainly nerve growth factor (NGF from the hippocampus. Axotomy of cholinergic neurons induces a reduction in the number of neurons positive for cholinergic markers in the medial septum. In several studies, the reduction of cholinergic markers has been interpreted as analogous to the neurodegeneration of cholinergic cells, ruling out the possibility that neurons lose their cholinergic phenotype without dying. Understanding the mechanism of cholinergic neurodegeneration after axotomy is relevant, since this paradigm has been extensively explored as an animal model of the cholinergic impairment observed in neuropathologies such as Alzheimer's disease. The principal aim of this study was to evaluate, using modern quantitative confocal microscopy, neurodegenerative changes in septal cholinergic neurons after axotomy and to assess their response to delayed infusion of NGF in rats. Results We found that there is a slow reduction of cholinergic cells labeled by ChAT and p75 after axotomy. However, this phenomenon is not accompanied by neurodegenerative changes or by a decrease in total neuronal number in the medial septum. Although the remaining axotomized-neurons appear healthy, they are unable to respond to delayed NGF infusion. Conclusions Our results demonstrate that at 3 weeks, axotomized cholinergic neurons lose their cholinergic phenotype without dying and down-regulate their NGF-receptors, precluding the possibility of a response to NGF. Therefore, the physiological role of NGF in the adult septal cholinergic system is to support phenotypic differentiation and not survival

  3. Overnight fasting regulates inhibitory tone to cholinergic neurons of the dorsomedial nucleus of the hypothalamus.

    Directory of Open Access Journals (Sweden)

    Florian Groessl

    Full Text Available The dorsomedial nucleus of the hypothalamus (DMH contributes to the regulation of overall energy homeostasis by modulating energy intake as well as energy expenditure. Despite the importance of the DMH in the control of energy balance, DMH-specific genetic markers or neuronal subtypes are poorly defined. Here we demonstrate the presence of cholinergic neurons in the DMH using genetically modified mice that express enhanced green florescent protein (eGFP selectively in choline acetyltransferase (Chat-neurons. Overnight food deprivation increases the activity of DMH cholinergic neurons, as shown by induction of fos protein and a significant shift in the baseline resting membrane potential. DMH cholinergic neurons receive both glutamatergic and GABAergic synaptic input, but the activation of these neurons by an overnight fast is due entirely to decreased inhibitory tone. The decreased inhibition is associated with decreased frequency and amplitude of GABAergic synaptic currents in the cholinergic DMH neurons, while glutamatergic synaptic transmission is not altered. As neither the frequency nor amplitude of miniature GABAergic or glutamatergic postsynaptic currents is affected by overnight food deprivation, the fasting-induced decrease in inhibitory tone to cholinergic neurons is dependent on superthreshold activity of GABAergic inputs. This study reveals that cholinergic neurons in the DMH readily sense the availability of nutrients and respond to overnight fasting via decreased GABAergic inhibitory tone. As such, altered synaptic as well as neuronal activity of DMH cholinergic neurons may play a critical role in the regulation of overall energy homeostasis.

  4. To boost or not boost in radiotherapy

    International Nuclear Information System (INIS)

    The aim of this paper it to analyse and discuss standard definition of the 'boost' procedure in relation to clinical results and new forms of the boost designed on physical and radiobiological bases. Seventeen sets of clinical data including over 5000 cases cancer with different tumour stages and locations and treated with various forms of 'boost' method have been subtracted from literature. Effectiveness of boost is analyzed regarding its place in combined treatment, timing and subvolume involved. Radiobiological parameter of D10 and normalization method for biologically equivalent doses and dose intensity are used to simulated cold and not subvolumes (hills and dales) and its influence of effectiveness on the boost delivery. Sequential and concomitant boost using external irradiation, although commonly used, offers LTC benefit lower than expected. Brachytherapy, intraoperative irradiation and concurrent chemotherapy boost methods appear more effective. Conformal radiotherapy, with or without dose-intensity modulation, allows heterogeneous increase in dose intensity within the target volume and can be used to integrate the 'boost dose' into baseline treatment (Simultaneous Integrated Boost and SIB). Analysis of interrelationships between boost-dose; boost volume and its timing shows that a TCP benefit from boosting can be expected when a relatively large part of the target volume is involved. Increase in boost dose above 1.2-1.3 of baseline dose using 'standard' methods does not substantially further increase the achieved TCP benefit unless hypoxic cells are a problem. Any small uncertainties in treatment planning can ruin all potential beneficial effect of the boost. For example, a 50% dose deficit in a very small (e.g. 1%) volume of target can decrease TCP to zero. Therefore boost benefits should be carefully weighed against any risk of cold spots in the target volume. Pros and cons in discussion of the role of boost in radiotherapy lead to the important

  5. Increasing bioavailability of (R)-alpha-lipoic acid to boost antioxidant activity in the treatment of neuropathic pain.

    Science.gov (United States)

    Maglione, Emilia; Marrese, Cinzia; Migliaro, Elisa; Marcuccio, Fortuna; Panico, Claudia; Salvati, Carmine; Citro, Giuseppe; Quercio, Marco; Roncagliolo, Federico; Torello, Carlo; Brufani, Mario

    2015-01-01

    a-lipoic acid (a-LA) is a potent natural antioxidant because it has a broad spectrum of action towards a great many free radical species and boosts the endogenous antioxidant systems.Although it is a multi-functional molecule, its pharmacokinetic characteristics pose restrictions to its use in the treatment of oxidative stress-dependent illnesses. Formulations that increase the bioavailability of a-LA have a better potential efficacy as adjuvants for the treatment of these conditions.This objective was achieved with a liquid formulation for oral use containing only R-aLA, the natural enantiomeric and most active form of a-lipoic acid.For the first time, the effects of this formulation were evaluated on neuropathic pain, a symptom caused by an increase in oxidative stress, regardless of the underlying cause. Neuropathic patients who have used this dietary supplement noticed an improvement in their quality of life and a significant reduction was observed in a number of certain descriptive pain parameters (intensity, burning, unpleasantness, superficial pain).Undoubtedly further, more in-depth, studies need to be conducted; however, this first investigation confirms the role of R-aLA as an anti-oxidant for the aetiological treatment of peripheral neuropathy. Increasing its plasma bioavailability even after a non-invasive administration through the oral route is a good starting point for proposing a valid adjuvant for the treatment of pain symptoms. PMID:26694149

  6. Megakaryocytopoiesis in culture: modulation by cholinergic mechanisms.

    Science.gov (United States)

    Burstein, S A; Adamson, J W; Harker, L A

    1980-05-01

    Treatment of murine bone marrow cultures with the cholinergic agonist carbamylcholine enhanced megakaryocytic colony growth by as much as 65%. In contrast, adrenergic agonists had no such effect. Addition to cultures of dibutyryl cyclic GMP (db-cGMP) also enhanced megakaryocytic colonies up to 50%, whereas dibutyryl cyclic AMP (db-cAMP) had no effect. Sodium nitroprusside and sodium nitrite, putative guanyl cyclase activators, also enhanced colony numbers, as did imidazole, a postulated cGMP phosphodiesterase inhibitor. Preincubation of marrow for two hours with carbamylcholine resulted both an increase in colony numbers (58%) and percent of progenitors in DNA synthesis (48%, compared to 14% for controls) as determined by tritiated thymidine suicide studies. Treatment of mice with the acetylcholinesterase inhibitor neostigmine resulted in an increase in CFU-M/humerus (62%) and percent in DNA synthesis (45%). These data indicate that 1) cholinergic, but not adrenergic, agonists modulate megakaryocytopoiesis in culture; 2) this effect may be mediated by cyclic GMP; and 3) only a brief period of exposure of marrow cells to agonist results in enhancement of megakaryocytic colonies. PMID:6108328

  7. A Tapped-Inductor Buck-Boost Converter for a Dielectric ElectroActive Polymer Generator

    DEFF Research Database (Denmark)

    Dimopoulos, Emmanouil; Munk-Nielsen, Stig

    2014-01-01

    Energy harvesting applications based on Dielectric ElectroActive Polymer (DEAP) generators have been in the spotlight in recent years after the latter ones’ documented advantages against competing electromagnetic and field-activated technologies. Yet, the need for bidirectional energy flow under...... high step-up and high step-down voltage conversion ratios, accompanied by low-average but relatively high-peak currents, imposes great challenges on the design of the employed power electronic converter. In addition, the effective operational range of the converter is usually limited by the lack of...

  8. Others' Sheer Presence Boosts Brain Activity in the Attention (But Not the Motivation) Network.

    Science.gov (United States)

    Monfardini, Elisabetta; Redouté, Jérôme; Hadj-Bouziane, Fadila; Hynaux, Clément; Fradin, Jacques; Huguet, Pascal; Costes, Nicolas; Meunier, Martine

    2016-06-01

    The sheer presence of another member of the same species affects performance, sometimes impeding it, sometimes enhancing it. For well-learned tasks, the effect is generally positive. This fundamental form of social influence, known as social facilitation, concerns human as well as nonhuman animals and affects many behaviors from food consumption to cognition. In psychology, this phenomenon has been known for over a century. Yet, its underlying mechanism (motivation or attention) remains debated, its relationship to stress unclear, and its neural substrates unknown. To address these issues, we investigated the behavioral, neuronal, and endocrinological markers of social facilitation in monkeys trained to touch images to obtain rewards. When another animal was present, performance was enhanced, but testing-induced stress (i.e., plasma cortisol elevation) was unchanged, as was metabolic activity in the brain motivation network. Rather, task-related activity in the (right) attention frontoparietal network encompassing the lateral prefrontal cortex, ventral premotor cortex, frontal eye field, and intraparietal sulcus was increased when another individual was present compared with when animals were tested alone. These results establish the very first link between the behavioral enhancement produced by the mere presence of a peer and an increase of metabolic activity in those brain structures underpinning attention. PMID:25858969

  9. Eosinophil-Mediated Cholinergic Nerve Remodeling

    OpenAIRE

    Durcan, Niamh; Costello, Richard W; McLean, W. Graham; Blusztajn, Jan; Madziar, Beata; Fenech, Anthony G; Hall, Ian P; Gleich, Gerard J.; McGarvey, Lorcan; Walsh, Marie-Therese

    2006-01-01

    Eosinophils are observed to localize to cholinergic nerves in a variety of inflammatory conditions such as asthma, rhinitis, eosinophilic gastroenteritis, and inflammatory bowel disease, where they are also responsible for the induction of cell signaling.Wehypothesized that a consequence of eosinophil localization to cholinergic nerves would involve a neural remodeling process. Eosinophil co-culture with cholinergic IMR32 cells led to increased expression of the M2 muscar...

  10. Removing undesirable color and boosting biological activity in red beet extracts using gamma irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Seung Sik; Lee, Eun Mi; Hong, Sung Hyun; Bai, Hyoung Woo; Chung, Byung Yeoup [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of); Lee, In Chul [Youngdong University, Youngdong (Korea, Republic of)

    2011-10-15

    Red beet (Beta vulgaris L.) is a traditional and popular vegetable distributed in many part of the world and has been used as a natural colorant in many dairy products, beverages, candies and cattle products. Red beet roots contain two groups of betalain pigments, redviolet betacyanins and yellow betaxanthins. Betalains possess several biological activities such as antioxidant, anti-inflammatory, hepatoprotective, and anticancer properities. Recent trend of using natural products in industries tends toward multifunctional, high quality, and highpriced value foods and cosmetics. To meet the needs of consumers, cosmetics, medicine, and foods should contain the proper amount of natural products. Although the color removal processes such as filtration and absorption by clay are still useful, these procedures are difficult, time-consuming and costly. To overcome this problem, the radiation technology has emerged as a new way. Radiation technology has been applied to the decomposition and decoloration of pigment and is an efficient technique for inactivating pathogens, removing undesirable color in biomaterial extracts and improving or maintaining biological activities. Gamma-irradiation and electron beamirradiation techniques in previous reports were applied in order to remove any undesirable color and to improve or maintain biological activities of various extracts such as green tea leaves, licorice root, and S. chinensis fruits. Latorre et al. reported that betacyanin concentration decreased with the irradiation dose and significantly, in 35%, after 2.0 kGy of gamma-ray, whereas betaxathin concentration increased (about 11%-ratio with respect to control) after 1 kGy but decreased (about 19%) after 2 kGy. However, they did not try to analysis for completed removal of red beet pigments. Therefore, it is necessary to find the optimum irradiation dose for entirely removing red pigments in red beet. The aim of this work was to address the effects of the color removal and

  11. Removing undesirable color and boosting biological activity in red beet extracts using gamma irradiation

    International Nuclear Information System (INIS)

    Red beet (Beta vulgaris L.) is a traditional and popular vegetable distributed in many part of the world and has been used as a natural colorant in many dairy products, beverages, candies and cattle products. Red beet roots contain two groups of betalain pigments, redviolet betacyanins and yellow betaxanthins. Betalains possess several biological activities such as antioxidant, anti-inflammatory, hepatoprotective, and anticancer properities. Recent trend of using natural products in industries tends toward multifunctional, high quality, and highpriced value foods and cosmetics. To meet the needs of consumers, cosmetics, medicine, and foods should contain the proper amount of natural products. Although the color removal processes such as filtration and absorption by clay are still useful, these procedures are difficult, time-consuming and costly. To overcome this problem, the radiation technology has emerged as a new way. Radiation technology has been applied to the decomposition and decoloration of pigment and is an efficient technique for inactivating pathogens, removing undesirable color in biomaterial extracts and improving or maintaining biological activities. Gamma-irradiation and electron beamirradiation techniques in previous reports were applied in order to remove any undesirable color and to improve or maintain biological activities of various extracts such as green tea leaves, licorice root, and S. chinensis fruits. Latorre et al. reported that betacyanin concentration decreased with the irradiation dose and significantly, in 35%, after 2.0 kGy of gamma-ray, whereas betaxathin concentration increased (about 11%-ratio with respect to control) after 1 kGy but decreased (about 19%) after 2 kGy. However, they did not try to analysis for completed removal of red beet pigments. Therefore, it is necessary to find the optimum irradiation dose for entirely removing red pigments in red beet. The aim of this work was to address the effects of the color removal and

  12. Boosting Active Contours for Weld Pool Visual Tracking in Automatic Arc Welding

    DEFF Research Database (Denmark)

    Liu, Jinchao; Fan, Zhun; Olsen, Søren Ingvor;

    2015-01-01

    Detecting the shape of the non-rigid molten metal during welding, so-called weld pool visual sensing, is one of the central tasks for automating arc welding processes. It is challenging due to the strong interference of the high-intensity arc light and spatters as well as the lack of robust...... approaches to detect and represent the shape of the nonrigid weld pool. We propose a solution using active contours including an prior for the weld pool boundary composition. Also, we apply Adaboost to select a small set of features that captures the relevant information. The proposed method is applied to...... weld pool tracking and the presented results verified its feasibility....

  13. Cholinergic modulation of event-related oscillations (ERO).

    Science.gov (United States)

    Sanchez-Alavez, Manuel; Robledo, Patricia; Wills, Derek N; Havstad, James; Ehlers, Cindy L

    2014-04-22

    The cholinergic system in the brain modulates patterns of activity involved in general arousal, attention processing, memory and consciousness. In the present study we determined the effects of selective cholinergic lesions of the medial septum area (MS) or nucleus basalis magnocellularis (NBM) on amplitude and phase characteristics of event related oscillations (EROs). A time-frequency based representation was used to determine ERO energy, phase synchronization across trials, recorded within a structure (phase lock index, PLI), and phase synchronization across trials, recorded between brain structures (phase difference lock index, PDLI), in the frontal cortex (Fctx), dorsal hippocampus (DHPC) and central amygdala (Amyg). Lesions in MS produced: (1) decreases in ERO energy in delta, theta, alpha, beta and gamma frequencies in Amyg, (2) reductions in gamma ERO energy and PLI in Fctx, (3) decreases in PDLI between the Fctx-Amyg in the theta, alpha, beta and gamma frequencies, and (4) decreases in PDLI between the DHPC-Amyg and Fctx-DHPC in the theta frequency bands. Lesions in NBM resulted in: (1) increased ERO energy in delta and theta frequency bands in Fctx, (2) reduced gamma ERO energy in Fctx and Amyg, (3) reductions in PLI in the theta, beta and gamma frequency ranges in Fctx, (4) reductions in gamma PLI in DHPC and (5) reduced beta PLI in Amyg. These studies suggest that the MS cholinergic system can alter phase synchronization between brain areas whereas the NBM cholinergic system modifies phase synchronization/phase resetting within a brain area. PMID:24594019

  14. [Involvement and plasticity of brainstem cholinergic neurons in cocaine-induced addiction].

    Science.gov (United States)

    Kaneda, Katsuyuki; Shinohara, Fumiya; Kurosawa, Ryo; Taoka, Naofumi; Ide, Soichiro; Minami, Masabumi

    2014-04-01

    Although the involvement and plasticity of the mesocorticolimbic dopamine (DA) system in cocaine-induced addiction have been studied extensively, the role of the brainstem cholinergic system in cocaine addiction remains largely unexplored. The laterodorsal tegmental nucleus (LDT) contains cholinergic neurons that innervate the ventral tegmental area (VTA) and is crucial for regulating the activity of VTA DA neurons, implying that LDT may also be associated with cocaine addiction. In this review, we summarize our recent findings showing that cholinergic transmission from the LDT to the VTA is involved in acquisition and expression of cocaine-induced conditioned place preference and that, after repeated cocaine exposures, these neurons exhibit synaptic plasticity, which is dependent on NMDA receptor activation, nitric oxide production, and the activity of medial prefrontal cortex. The findings strongly suggest that LDT cholinergic neurons may critically contribute to developing cocaine-induced addiction. PMID:24946392

  15. GABAergic actions on cholinergic laterodorsal tegmental neurons

    DEFF Research Database (Denmark)

    Kohlmeier, K A; Kristiansen, Uffe

    2010-01-01

    Cholinergic neurons of the pontine laterodorsal tegmentum (LDT) play a critical role in regulation of behavioral state. Therefore, elucidation of mechanisms that control their activity is vital for understanding of how switching between wakefulness, sleep and anesthetic states is effectuated. In...... vivo studies suggest that GABAergic mechanisms within the pons play a critical role in behavioral state switching. However, the postsynaptic, electrophysiological actions of GABA on LDT neurons, as well as the identity of GABA receptors present in the LDT mediating these actions is virtually unexplored...... neurons. Post-synaptic location of GABA(A) receptors was demonstrated by persistence of muscimol-induced inward currents in TTX and low Ca(2+) solutions. THIP, a selective GABA(A) receptor agonist with a preference for d-subunit containing GABA(A) receptors, induced inward currents, suggesting the...

  16. Inhibition of airway surface fluid absorption by cholinergic stimulation

    OpenAIRE

    Nam Soo Joo; Krouse, Mauri E.; Jae Young Choi; Hyung-Ju Cho; Wine, Jeffrey J.

    2016-01-01

    In upper airways airway surface liquid (ASL) depth and clearance rates are both increased by fluid secretion. Secretion is opposed by fluid absorption, mainly via the epithelial sodium channel, ENaC. In static systems, increased fluid depth activates ENaC and decreased depth inhibits it, suggesting that secretion indirectly activates ENaC to reduce ASL depth. We propose an alternate mechanism in which cholinergic input, which causes copious airway gland secretion, also inhibits ENaC-mediated ...

  17. Boosting foundations and algorithms

    CERN Document Server

    Schapire, Robert E

    2012-01-01

    Boosting is an approach to machine learning based on the idea of creating a highly accurate predictor by combining many weak and inaccurate "rules of thumb." A remarkably rich theory has evolved around boosting, with connections to a range of topics, including statistics, game theory, convex optimization, and information geometry. Boosting algorithms have also enjoyed practical success in such fields as biology, vision, and speech processing. At various times in its history, boosting has been perceived as mysterious, controversial, even paradoxical.

  18. A viral vectored prime-boost immunization regime targeting the malaria Pfs25 antigen induces transmission-blocking activity.

    Directory of Open Access Journals (Sweden)

    Anna L Goodman

    Full Text Available The ookinete surface protein Pfs25 is a macrogamete-to-ookinete/ookinete stage antigen of Plasmodium falciparum, capable of exerting high-level anti-malarial transmission-blocking activity following immunization with recombinant protein-in-adjuvant formulations. Here, this antigen was expressed in recombinant chimpanzee adenovirus 63 (ChAd63, human adenovirus serotype 5 (AdHu5 and modified vaccinia virus Ankara (MVA viral vectored vaccines. Two immunizations were administered to mice in a heterologous prime-boost regime. Immunization of mice with AdHu5 Pfs25 at week 0 and MVA Pfs25 at week 10 (Ad-MVA Pfs25 resulted in high anti-Pfs25 IgG titers, consisting of predominantly isotypes IgG1 and IgG2a. A single priming immunization with ChAd63 Pfs25 was as effective as AdHu5 Pfs25 with respect to ELISA titers at 8 weeks post-immunization. Sera from Ad-MVA Pfs25 immunized mice inhibited the transmission of P. falciparum to the mosquito both ex vivo and in vivo. In a standard membrane-feeding assay using NF54 strain P. falciparum, oocyst intensity in Anopheles stephensi mosquitoes was significantly reduced in an IgG concentration-dependent manner when compared to control feeds (96% reduction of intensity, 78% reduction in prevalence at a 1 in 5 dilution of sera. In addition, an in vivo transmission-blocking effect was also demonstrated by direct feeding of immunized mice infected with Pfs25DR3, a chimeric P. berghei line expressing Pfs25 in place of endogenous Pbs25. In this assay the density of Pfs25DR3 oocysts was significantly reduced when mosquitoes were fed on vaccinated as compared to control mice (67% reduction of intensity, 28% reduction in prevalence and specific IgG titer correlated with efficacy. These data confirm the utility of the adenovirus-MVA vaccine platform for the induction of antibodies with transmission-blocking activity, and support the continued development of this alternative approach to transmission-blocking malaria subunit

  19. Neuroinflammation not associated with cholinergic degeneration in aged-impaired brain

    OpenAIRE

    McQuail, Joseph A.; Riddle, David R.; Nicolle, Michelle M.

    2010-01-01

    Degeneration of the cholinergic neurons in the basal forebrain and elevation of inflammatory markers are well-established hallmarks of Alzheimer's disease; however, the interplay of these processes in normal aging is not extensively studied. Consequently, we conducted a neuroanatomical investigation to quantify cholinergic neurons and activated microglia in the medial septum/vertical diagonal band (MS/VDB) of young (6 months) and aged (28 months) Fisher 344 × Brown Norway F1 rats. Aged rats i...

  20. Neurostimulation of the Cholinergic Anti-Inflammatory Pathway Ameliorates Disease in Rat Collagen-Induced Arthritis

    OpenAIRE

    Levine, Yaakov A; Koopman, Frieda A.; Faltys, Michael; Caravaca, April; Bendele, Alison; Zitnik, Ralph; Vervoordeldonk, Margriet J.; Tak, Paul Peter

    2014-01-01

    Introduction The inflammatory reflex is a physiological mechanism through which the nervous system maintains immunologic homeostasis by modulating innate and adaptive immunity. We postulated that the reflex might be harnessed therapeutically to reduce pathological levels of inflammation in rheumatoid arthritis by activating its prototypical efferent arm, termed the cholinergic anti-inflammatory pathway. To explore this, we determined whether electrical neurostimulation of the cholinergic anti...

  1. Cholinergic enhancement of visual attention and neural oscillations in the human brain.

    OpenAIRE

    M. Bauer; C. Kluge; Bach, D.; Bradbury, D.; Heinze, H. J.; Dolan, R J; Driver, J.

    2012-01-01

    Summary Cognitive processes such as visual perception and selective attention induce specific patterns of brain oscillations [1–6]. The neurochemical bases of these spectral changes in neural activity are largely unknown, but neuromodulators are thought to regulate processing [7–9]. The cholinergic system is linked to attentional function in vivo [10–13], whereas separate in vitro studies show that cholinergic agonists induce high-frequency oscillations in slice preparations [14–16]. This has...

  2. Gut feeling: MicroRNA discriminators of the intestinal TLR9–cholinergic links

    OpenAIRE

    Nadorp, Bettina; Soreq, Hermona

    2015-01-01

    The intestinal tissue notably responds to stressful, cholinergic and innate immune signals by microRNA (miRNA) changes, but whether and how those miRNA regulators modify the intestinal cholinergic and innate immune pathways remained unexplored. Here, we report changes in several miRNA regulators of cholinesterases (ChEs) and correspondingly modified ChE activities in intestine, splenocytes and the circulation of mice exposed to both stress and canonical or alternative Toll-Like Receptor 9 (TL...

  3. Effects of cholinergic deafferentation of the rhinal cortex on visual recognition memory in monkeys

    Science.gov (United States)

    Turchi, Janita; Saunders, Richard C.; Mishkin, Mortimer

    2005-01-01

    Excitotoxic lesion studies have confirmed that the rhinal cortex is essential for visual recognition ability in monkeys. To evaluate the mnemonic role of cholinergic inputs to this cortical region, we compared the visual recognition performance of monkeys given rhinal cortex infusions of a selective cholinergic immunotoxin, ME20.4-SAP, with the performance of monkeys given control infusions into this same tissue. The immunotoxin, which leads to selective cholinergic deafferentation of the infused cortex, yielded recognition deficits of the same magnitude as those produced by excitotoxic lesions of this region, providing the most direct demonstration to date that cholinergic activation of the rhinal cortex is essential for storing the representations of new visual stimuli and thereby enabling their later recognition. PMID:15684066

  4. Choline metabolism as a basis for the selective vulnerability of cholinergic neurons

    Science.gov (United States)

    Wurtman, R. J.

    1992-01-01

    The unique propensity of cholinergic neurons to use choline for two purposes--ACh and membrane phosphatidylcholine synthesis--may contribute to their selective vulnerability in Alzheimer's disease and other cholinergic neurodegenerative disorders. When physiologically active, the neurons use free choline taken from the 'reservoir' in membrane phosphatidylcholine to synthesize ACh; this can lead to an actual decrease in the quantity of membrane per cell. Alzheimer's disease (but not Down's syndrome, or other neurodegenerative disorders) is associated with characteristic neurochemical lesions involving choline and ethanolamine: brain levels of these compounds are diminished, while those of glycerophosphocholine and glycerophosphoethanolamine (breakdown products of their respective membrane phosphatides) are increased, both in cholinergic and noncholinergic brain regions. Perhaps this metabolic disturbance and the tendency of cholinergic neurons to 'export' choline--in the form of ACh--underlie the selective vulnerability of the neurons. Resulting changes in membrane composition could abnormally expose intramembraneous proteins such as amyloid precursor protein to proteases.

  5. PET study of cholinergic system in the brain

    Energy Technology Data Exchange (ETDEWEB)

    Shinotoh, Hitoshi [Chiba Univ. (Japan). School of Medicine

    1999-01-01

    Recently, we have developed a method to measure acetylcholinesterase (AChE) activity, a functional marker for cholinergic system, by positron emission tomography (PET) and carbon-11 labeled N-methyl-4-piperidyl acetate. Kinetic analysis of the radioactivity in the brain and the plasma yielded a rate constant ``k 3`` as an index of AChE activity. The ratios for the k 3 values for the cerebral cortex/thalamus/cerebellum/striatum found in healthy participants were 1/ 3/ 8/ 10, respectively, corresponding well with AChE activity ratios in the brain at necropsy (1/ 3/ 8/ 38), except for the striatum. In 23 healthy volunteers (age range: 24-89 years), there was no age-related decline of k 3 values in the cerebral cortex, suggesting AChE activity is preserved in aged cerebral cortex. In 11 patients with Alzheimer`s disease, there was a significant reduction (-24%) of k 3 values in the cerebral cortex and hippocampus, suggesting a loss of ascending cholinergic system from the basal forebrain to the cerebral cortex and hippocampus. In 16 patients with Parkinson`s disease, there was a significant reduction (-18%) of k 3 values in the cerebral cortex. In 10 patients with progressive supra nuclear palsy, there was a significant reduction (-38%) of k 3 values in the thalamus. This technique is useful for investigating central cholinergic system in neuro degenerative disorders with dementia. (author)

  6. PET study of cholinergic system in the brain

    International Nuclear Information System (INIS)

    Recently, we have developed a method to measure acetylcholinesterase (AChE) activity, a functional marker for cholinergic system, by positron emission tomography (PET) and carbon-11 labeled N-methyl-4-piperidyl acetate. Kinetic analysis of the radioactivity in the brain and the plasma yielded a rate constant ''k 3'' as an index of AChE activity. The ratios for the k 3 values for the cerebral cortex/thalamus/cerebellum/striatum found in healthy participants were 1/ 3/ 8/ 10, respectively, corresponding well with AChE activity ratios in the brain at necropsy (1/ 3/ 8/ 38), except for the striatum. In 23 healthy volunteers (age range: 24-89 years), there was no age-related decline of k 3 values in the cerebral cortex, suggesting AChE activity is preserved in aged cerebral cortex. In 11 patients with Alzheimer's disease, there was a significant reduction (-24%) of k 3 values in the cerebral cortex and hippocampus, suggesting a loss of ascending cholinergic system from the basal forebrain to the cerebral cortex and hippocampus. In 16 patients with Parkinson's disease, there was a significant reduction (-18%) of k 3 values in the cerebral cortex. In 10 patients with progressive supra nuclear palsy, there was a significant reduction (-38%) of k 3 values in the thalamus. This technique is useful for investigating central cholinergic system in neuro degenerative disorders with dementia. (author)

  7. Evaluating the Evidence Surrounding Pontine Cholinergic Involvement in REM Sleep Generation

    Science.gov (United States)

    Grace, Kevin P.; Horner, Richard L.

    2015-01-01

    Rapid eye movement (REM) sleep – characterized by vivid dreaming, motor paralysis, and heightened neural activity – is one of the fundamental states of the mammalian central nervous system. Initial theories of REM sleep generation posited that induction of the state required activation of the “pontine REM sleep generator” by cholinergic inputs. Here, we review and evaluate the evidence surrounding cholinergic involvement in REM sleep generation. We submit that: (i) the capacity of pontine cholinergic neurotransmission to generate REM sleep has been firmly established by gain-of-function experiments, (ii) the function of endogenous cholinergic input to REM sleep generating sites cannot be determined by gain-of-function experiments; rather, loss-of-function studies are required, (iii) loss-of-function studies show that endogenous cholinergic input to the PTF is not required for REM sleep generation, and (iv) cholinergic input to the pontine REM sleep generating sites serve an accessory role in REM sleep generation: reinforcing non-REM-to-REM sleep transitions making them quicker and less likely to fail. PMID:26388832

  8. Evaluating the evidence surrounding pontine cholinergic involvement in REM sleep generation

    Directory of Open Access Journals (Sweden)

    Kevin P Grace

    2015-09-01

    Full Text Available Rapid eye movement (REM sleep - characterized by vivid dreaming, motor paralysis, and heightened neural activity - is one of the fundamental states of the mammalian central nervous system. Initial theories of rapid eye movement (REM sleep generation posited that induction of the state required activation of the ‘pontine REM sleep generator’ by cholinergic inputs. Here we review and evaluate the evidence surrounding cholinergic involvement in REM sleep generation. We submit that: (i the capacity of pontine cholinergic neurotransmission to generate REM sleep has been firmly established by gain-of-function experiments, (ii the function of endogenous cholinergic input to REM sleep generating sites cannot be determined by gain-of-function experiments; rather, loss-of-function studies are required, (iii loss-of-function studies show that endogenous cholinergic input to the PFT is not required for REM sleep generation, and (iv Cholinergic input to the pontine REM sleep generating sites serve an accessory role in REM sleep generation: reinforcing non-REM-to-REM sleep transitions making them quicker and less likely to fail.

  9. Can you boost your metabolism?

    Science.gov (United States)

    ... more calories than fat. So will building more muscle not boost your metabolism? Yes, but only by a small amount. Most ... you burn. Plus, when not in active use, muscles burn very few calories. Most ... most of your metabolism. What to do: Lift weights for stronger bones ...

  10. A cholinergic hypothesis of the unconscious in affective disorders.

    Directory of Open Access Journals (Sweden)

    Costa eVakalopoulos

    2013-11-01

    Full Text Available The interactions between distinct pharmacological systems are proposed as a key dynamic in the formation of unconscious memories underlying rumination and mood disorder, but also reflect the plastic capacity of neural networks that can aid recovery. An inverse and reciprocal relationship is postulated between cholinergic and monoaminergic receptor subtypes. M1-type muscarinic receptor transduction facilitates encoding of unconscious, prepotent behavioural repertoires at the core of affective disorders and ADHD. Behavioural adaptation to new contingencies is mediated by the classic prototype receptor: 5-HT1A (Gi/o and its modulation of m1-plasticity. Reversal of learning is dependent on increased phasic activation of midbrain monoaminergic nuclei and is a function of hippocampal theta. Acquired hippocampal dysfunction due to abnormal activation of the hypothalamic-pituitary-adrenal (HPA axis predicts deficits in hippocampal-dependent memory and executive function and further impairments to cognitive inhibition. Encoding of explicit memories is mediated by Gq/11 and Gs signalling of monoamines only. A role is proposed for the phasic activation of the basal forebrain cholinergic nucleus by cortical projections from the complex consisting of the insula and claustrum. Although controversial. recent studies suggest a common ontogenetic origin of the two structures and a functional coupling. Lesions of the region result in loss of motivational behaviour and familiarity based judgements. A major hypothesis of the paper is that these lost faculties result indirectly, from reduced cholinergic tone.

  11. The Cholinergic Signaling Responsible for the Expression of a Memory-Related Protein in Primary Rat Cortical Neurons.

    Science.gov (United States)

    Chen, Tsan-Ju; Chen, Shun-Sheng; Wang, Dean-Chuan; Hung, Hui-Shan

    2016-11-01

    Cholinergic dysfunction in the brain is closely related to cognitive impairment including memory loss. In addition to the degeneration of basal forebrain cholinergic neurons, deficits in the cholinergic receptor signaling may also play an important role. In the present study, to examine the cholinergic signaling pathways responsible for the induction of a memory-related postsynaptic protein, a cholinergic agonist carbachol was used to induce the expression of activity-regulated cytoskeleton associated protein (Arc) in primary rat cortical neurons. After pretreating neurons with various antagonists or inhibitors, the levels of carbachol-induced Arc protein expression were detected by Western blot analysis. The results show that carbachol induces Arc protein expression mainly through activating M1 acetylcholine receptors and the downstream phospholipase C pathway, which may lead to the activation of the MAPK/ERK signaling pathway. Importantly, carbachol-mediated M2 receptor activation exerts negative effects on Arc protein expression and thus counteracts the enhanced effects of M1 activation. Furthermore, it is suggested for the first time that M1-mediated enhancement of N-methyl-D-aspartate receptor (NMDAR) responses, leading to Ca(2+) entry through NMDARs, contributes to carbachol-induced Arc protein expression. These findings reveal a more complete cholinergic signaling that is responsible for carbachol-induced Arc protein expression, and thus provide more information for developing treatments that can modulate cholinergic signaling and consequently alleviate cognitive impairment. J. Cell. Physiol. 231: 2428-2438, 2016. © 2016 Wiley Periodicals, Inc. PMID:26895748

  12. Analysis and Comparison Based on Component Stress Factor of Dual Active Bridge and Isolated Full Bridge Boost Converters for Bidirectional Fuel Cells Systems

    DEFF Research Database (Denmark)

    Pittini, Riccardo; Mira Albert, Maria del Carmen; Zhang, Zhe;

    2014-01-01

    This paper presents an analysis and comparison of isolated topologies for bidirectional fuel cell systems. The analyzed topologies are the dua l active bridge (DAB) and the isolated full bridge boost converter (IFBBC). The analysis is performed based on the component stress factor (CSF). Results...... highlight that the DAB has lower CSF than the IFBBC for narrow converter operating points. On the other hand the IFBBC presents a more homogeneous CSF over the entire converter operating range. Finally, experimental results obtained from a 30-80 V 80 A 6 kW 40 kHz IFBBC are presented. The converter achieves...

  13. A High Efficient Improved Soft Switched Interleaved Boost Converter

    OpenAIRE

    A High Efficient Improved Soft Switched Interleaved Boost Converter

    2013-01-01

    In this paper an improved ZVT interleaved boost PFC topology is introduced. The proposed ZVT interleaved boost converter is composed of two cell boost conversion units and an active auxiliary circuit. The proposed converter has two important advantages over the similar soft switching converters. The first one is that parallel to the main switches of the converter the auxiliary switch also operates under soft switching condition. Providing soft switching conditions for interleaved boost conver...

  14. Striatal Cholinergic Neurotransmission Requires VGLUT3

    OpenAIRE

    Nelson, Alexandra B.; Bussert, Timothy G.; Kreitzer, Anatol C.; Seal, Rebecca P.

    2014-01-01

    It is now clear that many neuronal populations release more than one classical neurotransmitter, yet in most cases the functional role of corelease is unknown. Striatal cholinergic interneurons release both glutamate and acetylcholine, and vesicular loading of glutamate has been shown to enhance acetylcholine content. Using a combination of optogenetics and whole-cell recordings in mice, we now provide physiological evidence that optogenetic stimulation of cholinergic interneurons triggers mo...

  15. A case of postganglionic cholinergic dysautonomia.

    OpenAIRE

    Takayama, H; Kazahaya, Y; Kashihara, N.; Kuroda, H.; Miyawaki, S; Ota, Z; Ogawa, N.

    1987-01-01

    A 24 year old female presented with signs and symptoms of postganglionic cholinergic autonomic dysfunction manifested by impaired lachrymation and salivation, mydriasis of the pupil, decreased gastrointestinal motility, atony of the bladder, and sweating and taste disturbance. Clinical and pharmacological studies confirmed that the abnormalities were restricted mainly to the postganglionic cholinergic autonomic systems. The titre of serum complement was low, antinuclear antibodies revealed a ...

  16. Cholinergic mediation of small intestinal transit in the rat

    International Nuclear Information System (INIS)

    It has been reported that small intestinal transit (SIT) in the rat is not cholinergically mediated. The geometric mean of a marker may be a more powerful method for SIT studies. Therefore, it was their goal to evaluate the effect of muscarinic blockade in normal and prostaglandin E2 (PGE2)-enhanced SIT using this method. Male, food-fasted rats (190 to 240 g) were first dosed subcutaneously with atropine. 30 min after the atropine the rats received an oral dose of PGE2 at 5.0 mg/kg. 5 min after PGE2, a 51Cr-labeled marker was dosed intraduodenally, and a 25 min transit period followed. The results are: (1) 5.0 mg/kg of PGE2 significantly stimulates the geometric mean of the marker in agreement with previous findings and (2) atropine is inhibitory at doses as low as 0.20 mg/kg for basal SIT and 0.10 mg/kg for PGE2-stimulated SIT. This indicates (1) the rat has cholinergically mediated SIT, and (2) cholinergic activation may be important for PGE2 effects on SIT in the rat

  17. Learning Boost C++ libraries

    CERN Document Server

    Mukherjee, Arindam

    2015-01-01

    If you are a C++ programmer who has never used Boost libraries before, this book will get you up-to-speed with using them. Whether you are developing new C++ software or maintaining existing code written using Boost libraries, this hands-on introduction will help you decide on the right library and techniques to solve your practical programming problems.

  18. A more robust boosting algorithm

    OpenAIRE

    Freund, Yoav

    2009-01-01

    We present a new boosting algorithm, motivated by the large margins theory for boosting. We give experimental evidence that the new algorithm is significantly more robust against label noise than existing boosting algorithm.

  19. Metformin may antagonize Lin28 and/or Lin28B activity, thereby boosting let-7 levels and antagonizing cancer progression.

    Science.gov (United States)

    McCarty, Mark F

    2012-02-01

    Cancer cells with stem cell characteristics are harbored by most tumors, and are characterized by epithelial-mesenchymal transition (EMT) - which promotes invasive growth and metastasis - chemoresistance, and the capacity to reconstitute new tumors. Hence, the control or destruction of cancer stem cells should be a major goal of cancer management. The let-7 family of microRNAs has cancer suppressor activity, and recent evidence suggests that markedly reduced levels of let-7 are not only a typical feature of cancer stem cells, but may be largely responsible for cancer stemness. It is therefore particularly intriguing that metformin, a diabetes drug thought to have potential in the prevention and treatment of cancer, has recently been found to oppose cancer cell stemness, to markedly potentiate chemotherapeutic control of cancer in mouse xenograft models, and to notably boost let-7a levels in cancer stem cells. It is proposed that this latter effect of metformin may reflect AMPK-mediated inhibition of the expression or activity of Lin28/Lin28A, proteins which act post-transcriptionally to decrease the levels of all let-7 family members. The transcription of Lin28B is promoted by NF-kappaB and by Myc; hence, practical measures which antagonize NF-kappaB or Myc activity may complement the utility of metformin for boosting let-7 expression and controlling cancer stemness; salsalate, antioxidants, tyrosine kinase and cox-2 inhibitors, ribavirin, vitamin D, gamma-secretase inhibitors (when available), and parenteral curcumin may have some utility in this regard. Although the impact of histone deacetylase inhibitors on let-7 expression has not been assessed, there is reason to suspect that these drugs might complement let-7's impact on chemoresistance, EMT, and stemness. Multifocal strategies centering on metformin may have considerable potential for reversing cancer stemness and rendering advanced cancers more susceptible to long term control. PMID:22129484

  20. Effects of metoclopramide and domperidone on cholinergically mediated contractions of human isolated stomach muscle.

    Science.gov (United States)

    Sanger, G J

    1985-09-01

    The experiments examine the actions of metoclopramide and domperidone on the responses evoked by electrical field stimulation or by acetylcholine, in longitudinal muscle strips obtained from human stomach. Electrical field stimulation evoked contractions which were predominantly cholinergically mediated; metoclopramide 0.28-28 microM caused a concentration-dependent increase in the height of these contractions. In the presence of atropine and barium chloride, electrical stimulation evoked relaxations of the stomach muscle, probably by stimulating non-adrenergic, non-cholinergic inhibitory nerves; metoclopramide 28 microM had no effect on these relaxations. Metoclopramide 0.003-2.8 microM had no effect on contractions evoked by exogenous acetylcholine, although higher concentrations of the drug increased the contractions. The results suggest that in human isolated stomach, low concentrations of metoclopramide may increase electrically evoked cholinergic activity by increasing the release of neuronal acetylcholine. Stimulation by metoclopramide of cholinergic activity in the gut may therefore be an important mechanism by which the drug increases gastrointestinal motility during therapy. Cholinergically mediated contractions were not increased by domperidone, and other mechanism(s) of action may therefore be important for this drug. PMID:2867191

  1. Aging of cholinergic synapses: fiction or reality?

    International Nuclear Information System (INIS)

    The authors make use of the ciliary ganglion iris preparation of the aging chicken as a model of senescent peripheral cholinergic synapses. Based on the studies performed on the iris, an hypothesis of aging of the cholinergic synapse has been suggested. In order to establish the nature of a deficit, the authors examine the ability of chloinergic synapses in the iris at various ages to take up the precursor tritium-choline and release the formed tritium-ACh in response to high K+ (115 mM) depolarization. A summary of preliminary results of morphometric analysis of nerve endings and synaptic components in the iris of young adult and aged chickens is shown. The experiments suggest that severe changes may occur at later stages of life. A specific functional defect in the cholinergic synapse during aging is found

  2. Cholinergic regulation of the vasopressin neuroendocrine system

    Energy Technology Data Exchange (ETDEWEB)

    Michels, K.M.

    1987-01-01

    To clarify the physical and functional relationship between the cholinergic system, and the neurodocrine cells of the supraoptic nucleus, a combination of experiments on receptor binding, localization and function were carried out. The putative nicotinic receptor probe (/sup 125/I)alpha bungarotoxin ((/sup 125/I)alpha BTX) bound with high affinity and specificity to the vasopressin and oxytocin magnocellular neurons of the supraoptic nucleus, nucleus circularis, and paraventricular nucleus. Binding of (/sup 125/I)alpha BTX within the neural lobe was very low. In contrast, the muscarinic cholinergic receptor probe (/sup 3/H)quinuclidinylbenzilate ((/sup 3/H)QNB) did not bind to magnocellular vasopressin and oxytocin cell groups. The median eminence, which contains the neurosecretory axons, and the neural lobe of the pituitary contain low levels of (/sup 3/H)QNB binding. The physiological significance of these cholinergic receptors in regulation of vasopressin release was tested using an in vitro preparation of the supraoptic - neural lobe system.

  3. State dependency of the effects of microinjection of cholinergic drugs into the nucleus pontis oralis.

    Science.gov (United States)

    López-Rodríguez, F; Kohlmeier, K; Morales, F R; Chase, M H

    1994-06-27

    The microinjection of cholinergic drugs into the pontine reticular formation elicits active sleep-like states that are comprised of the principal physiological patterns of activity that characterize naturally-occurring active sleep, i.e., EEG desynchronization, PGO waves, rapid eye movements and atonia. We have reported that other behavioral states arise even when cholinergic drugs are injected into the exact same reticular location. The present study was conducted to explore the basis for the differences in the drug effect. A combination of acetylcholine and neostigmine was injected by microiontophoresis into the dorsal region of the nucleus pontis oralis in four chronic, unanesthetized cats. The states that were induced by cholinergic drug injection depended on the state of the animal at the time of the injection. When the animal was awake, cholinergic injections resulted in a waking-dissociated state, which was characterized by EEG desynchronization and muscle atonia in a cat that appeared to be awake and was able to track objects in its visual field. If the cat was in quiet sleep at the time of the injection, an active sleep-like state followed that was indistinguishable from naturally-occurring active sleep; on a few occasions following cholinergic injections during quiet sleep there was a quiet sleep-dissociated state, which was characterized by PGO waves and muscle atonia in the cat that by other indices appeared to be in quiet sleep. The results of this study indicate that the state of the animal at the time of drug injection is a critical variable that influences the responses which are induced by cholinergic stimulation of the pontine reticular formation. PMID:7953643

  4. Online Gradient Boosting

    OpenAIRE

    Beygelzimer, Alina; Hazan, Elad; Kale, Satyen; Luo, Haipeng

    2015-01-01

    We extend the theory of boosting for regression problems to the online learning setting. Generalizing from the batch setting for boosting, the notion of a weak learning algorithm is modeled as an online learning algorithm with linear loss functions that competes with a base class of regression functions, while a strong learning algorithm is an online learning algorithm with convex loss functions that competes with a larger class of regression functions. Our main result is an online gradient b...

  5. Modeling the Interaction between β-Amyloid Aggregates and Choline Acetyltransferase Activity and Its Relation with Cholinergic Dysfunction through Two-Enzyme/Two-Compartment Model

    Directory of Open Access Journals (Sweden)

    Hedia Fgaier

    2015-01-01

    Full Text Available The effect of β-amyloid aggregates on activity of choline acetyltransferase (ChAT which is responsible for synthesizing acetylcholine (ACh in human brain is investigated through the two-enzyme/two-compartment (2E2C model where the presynaptic neuron is considered as compartment 1 while both the synaptic cleft and the postsynaptic neuron are considered as compartment 2 through suggesting three different kinetic mechanisms for the inhibition effect. It is found that the incorporation of ChAT inhibition by β-amyloid aggregates into the 2E2C model is able to yield dynamic solutions for concentrations of generated β-amyloid, ACh, choline, acetate, and pH in addition to the rates of ACh synthesis and ACh hydrolysis in compartments 1 and 2. It is observed that ChAT activity needs a high concentration of β-amyloid aggregates production rate. It is found that ChAT activity is reduced significantly when neurons are exposed to high levels of β-amyloid aggregates leading to reduction in levels of ACh which is one of the most significant physiological symptoms of AD. Furthermore, the system of ACh neurocycle is dominated by the oscillatory behavior when ChAT enzyme is completely inhibited by β-amyloid. It is observed that the direct inactivation of ChAT by β-amyloid aggregates may be a probable mechanism contributing to the development of AD.

  6. Adult Mouse Basal Forebrain Harbors Two Distinct Cholinergic Populations Defined By Their Electrophysiology

    Directory of Open Access Journals (Sweden)

    Jorge P Golowasch

    2012-05-01

    Full Text Available We performed whole-cell recordings from basal forebrain cholinergic neurons in transgenic mice expressing enhanced green fluorescent protein under the control of choline acetyltransferase promoter. Basal forebrain cholinergic neurons can be differentiated into two electrophysiologically identifiable subtypes: early and late firing neurons. Early firing neurons (70% are more excitable, show prominent spike frequency adaptation and more susceptible to depolarization blockade, a phenomenon characterized by complete silencing of the neuron following initial action potentials. Late firing neurons (30%, albeit being less excitable, could maintain a tonic discharge at low frequencies. In voltage clamp analysis, we have shown that early firing neurons have a higher density of low voltage activated calcium currents. These two cholinergic cell populations might be involved in distinct functions: the early firing group being more suitable for phasic changes in cortical acetylcholine release associated with attention while the late firing neurons could support general arousal by maintaining tonic acetylcholine level.

  7. Attenuation of neuroinflammation by dexmedetomidine is associated with activation of a cholinergic anti-inflammatory pathway in a rat tibial fracture model.

    Science.gov (United States)

    Zhu, Ya-Juan; Peng, Ke; Meng, Xiao-Wen; Ji, Fu-Hai

    2016-08-01

    Sustained neuroinflammation contributes to the pathogenesis of postoperative cognitive dysfunction. Dexmedetomidine, a selective α-2 adrenergic receptor agonist, exhibits a protective role in the brain. This study investigated whether dexmedetomidine pretreatment attenuates neuroinflammation induced by tibial fracture in rats, as well as the mechanism by which dexmedetomidine provides its neuroprotection. In our study, we observed that tibial fracture significantly increased the levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) and the expression of nuclear factor-kappa B (NF-κB) in the hippocampus. Overexpression of microglial (CD11b) and astrocytic (GFAP) responses to injury were observed in the hippocampus. Dexmedetomidine pretreatment significantly suppressed the inflammatory responses, as evidenced by lower TNF-α and IL-1β levels, significantly inhibited NF-κB activity, and alleviated overexpression of microglia and astrocytes in the hippocampus. However, pretreatment with dexmedetomidine failed to attenuate cytokine responses and activity of NF-κB, CD11b and GFAP after vagotomy or treatment with methyllycaconitine, an α-7 nicotinic acetylcholine receptor (α7nAChR) antagonist. These results suggest that pretreatment with dexmedetomidine may attenuate neuroinflammation caused by tibial fracture in rats through vagal-dependent and α7nAChR-dependent mechanisms. PMID:27163720

  8. Cholinergic imaging in dementia spectrum disorders.

    Science.gov (United States)

    Roy, Roman; Niccolini, Flavia; Pagano, Gennaro; Politis, Marios

    2016-07-01

    The multifaceted nature of the pathology of dementia spectrum disorders has complicated their management and the development of effective treatments. This is despite the fact that they are far from uncommon, with Alzheimer's disease (AD) alone affecting 35 million people worldwide. The cholinergic system has been found to be crucially involved in cognitive function, with cholinergic dysfunction playing a pivotal role in the pathophysiology of dementia. The use of molecular imaging such as SPECT and PET for tagging targets within the cholinergic system has shown promise for elucidating key aspects of underlying pathology in dementia spectrum disorders, including AD or parkinsonian dementias. SPECT and PET studies using selective radioligands for cholinergic markers, such as [(11)C]MP4A and [(11)C]PMP PET for acetylcholinesterase (AChE), [(123)I]5IA SPECT for the α4β2 nicotinic acetylcholine receptor and [(123)I]IBVM SPECT for the vesicular acetylcholine transporter, have been developed in an attempt to clarify those aspects of the diseases that remain unclear. This has led to a variety of findings, such as cortical AChE being significantly reduced in Parkinson's disease (PD), PD with dementia (PDD) and AD, as well as correlating with certain aspects of cognitive function such as attention and working memory. Thalamic AChE is significantly reduced in progressive supranuclear palsy (PSP) and multiple system atrophy, whilst it is not affected in PD. Some of these findings have brought about suggestions for the improvement of clinical practice, such as the use of a thalamic/cortical AChE ratio to differentiate between PD and PSP, two diseases that could overlap in terms of initial clinical presentation. Here, we review the findings from molecular imaging studies that have investigated the role of the cholinergic system in dementia spectrum disorders. PMID:26984612

  9. Cholinergic imaging in dementia spectrum disorders

    Energy Technology Data Exchange (ETDEWEB)

    Roy, Roman; Niccolini, Flavia; Pagano, Gennaro; Politis, Marios [Institute of Psychiatry, Psychology and Neuroscience, King' s College London, Neurodegeneration Imaging Group, Department of Basic and Clinical Neuroscience, London (United Kingdom)

    2016-07-15

    The multifaceted nature of the pathology of dementia spectrum disorders has complicated their management and the development of effective treatments. This is despite the fact that they are far from uncommon, with Alzheimer's disease (AD) alone affecting 35 million people worldwide. The cholinergic system has been found to be crucially involved in cognitive function, with cholinergic dysfunction playing a pivotal role in the pathophysiology of dementia. The use of molecular imaging such as SPECT and PET for tagging targets within the cholinergic system has shown promise for elucidating key aspects of underlying pathology in dementia spectrum disorders, including AD or parkinsonian dementias. SPECT and PET studies using selective radioligands for cholinergic markers, such as [{sup 11}C]MP4A and [{sup 11}C]PMP PET for acetylcholinesterase (AChE), [{sup 123}I]5IA SPECT for the α{sub 4}β{sub 2} nicotinic acetylcholine receptor and [{sup 123}I]IBVM SPECT for the vesicular acetylcholine transporter, have been developed in an attempt to clarify those aspects of the diseases that remain unclear. This has led to a variety of findings, such as cortical AChE being significantly reduced in Parkinson's disease (PD), PD with dementia (PDD) and AD, as well as correlating with certain aspects of cognitive function such as attention and working memory. Thalamic AChE is significantly reduced in progressive supranuclear palsy (PSP) and multiple system atrophy, whilst it is not affected in PD. Some of these findings have brought about suggestions for the improvement of clinical practice, such as the use of a thalamic/cortical AChE ratio to differentiate between PD and PSP, two diseases that could overlap in terms of initial clinical presentation. Here, we review the findings from molecular imaging studies that have investigated the role of the cholinergic system in dementia spectrum disorders. (orig.)

  10. Roundup® exposure promotes gills and liver impairments, DNA damage and inhibition of brain cholinergic activity in the Amazon teleost fish Colossoma macropomum.

    Science.gov (United States)

    Braz-Mota, Susana; Sadauskas-Henrique, Helen; Duarte, Rafael M; Val, Adalberto L; Almeida-Val, Vera M F

    2015-09-01

    Roundup Original® (RD) is a glyphosate-based herbicide used to control weeds in agriculture. Contamination of Amazon waters has increased as a consequence of anthropogenic pressure, including the use of herbicides as RD. The central goal of this study was to evaluate the toxic effects of RD on juveniles of tambaqui (Colossoma macropomum). Our findings show that biomarkers in tambaqui are organ specific and dependent on RD concentration. Alterations in gills structural and respiratory epithelium were followed by changes in hematological parameters such as concentration of hemoglobin, particularly in fish exposed to the higher concentration tested (75% of RD LC50 96 h). In addition, both RD concentrations affected the biotransformation process in gills of tambaqui negatively. Instead, liver responses suggest that a production of reactive oxygen species (ROS) occurred in fish exposed to RD, particularly in the animals exposed to 75% RD, as seen by imbalances in biotransformation and antioxidant systems. The increased DNA damage observed in red blood cells of tambaqui exposed to RD is in agreement with this hypothesis. Finally, both tested sub-lethal concentrations of RD markedly inhibited the cholinesterase activity in fish brain. Thus, we can suggest that RD is potentially toxic to tambaqui and possibly to other tropical fish species. PMID:25898390

  11. Novel aspects of cholinergic regulation of colonic ion transport.

    Science.gov (United States)

    Bader, Sandra; Diener, Martin

    2015-06-01

    Nicotinic receptors are not only expressed by excitable tissues, but have been identified in various epithelia. One aim of this study was to investigate the expression of nicotinic receptors and their involvement in the regulation of ion transport across colonic epithelium. Ussing chamber experiments with putative nicotinic agonists and antagonists were performed at rat colon combined with reverse transcription polymerase chain reaction (RT-PCR) detection of nicotinic receptor subunits within the epithelium. Dimethylphenylpiperazinium (DMPP) and nicotine induced a tetrodotoxin-resistant anion secretion leading to an increase in short-circuit current (I sc) across colonic mucosa. The response was suppressed by the nicotinic receptor antagonist hexamethonium. RT-PCR experiments revealed the expression of α2, α4, α5, α6, α7, α10, and β4 nicotinic receptor subunits in colonic epithelium. Choline, the product of acetylcholine hydrolysis, is known for its affinity to several nicotinic receptor subtypes. As a strong acetylcholinesterase activity was found in colonic epithelium, the effect of choline on I sc was examined. Choline induced a concentration-dependent, tetrodotoxin-resistant chloride secretion which was, however, resistant against hexamethonium, but was inhibited by atropine. Experiments with inhibitors of muscarinic M1 and M3 receptors revealed that choline-evoked secretion was mainly due to a stimulation of epithelial M3 receptors. Although choline proved to be only a partial agonist, it concentration-dependently desensitized the response to acetylcholine, suggesting that it might act as a modulator of cholinergically induced anion secretion. Thus the cholinergic regulation of colonic ion transport - up to now solely explained by cholinergic submucosal neurons stimulating epithelial muscarinic receptors - is more complex than previously assumed. PMID:26236483

  12. Long-Term Effects of Maternal Deprivation on Cholinergic System in Rat Brain

    Directory of Open Access Journals (Sweden)

    Branka Marković

    2014-01-01

    Full Text Available Numerous clinical studies have demonstrated an association between early stressful life events and adult life psychiatric disorders including schizophrenia. In rodents, early life exposure to stressors such as maternal deprivation (MD produces numerous hormonal, neurochemical, and behavioral changes and is accepted as one of the animal models of schizophrenia. The stress induces acetylcholine (Ach release in the forebrain and the alterations in cholinergic neurotransmitter system are reported in schizophrenia. The aim of this study was to examine long-term effects of maternal separation on acetylcholinesterase (AChE activity in different brain structures and the density of cholinergic fibers in hippocampus and retrosplenial (RS cortex. Wistar rats were separated from their mothers on the postnatal day (P 9 for 24 h and sacrificed on P60. Control group of rats was bred under the same conditions, but without MD. Brain regions were collected for AChE activity measurements and morphometric analysis. Obtained results showed significant decrease of the AChE activity in cortex and increase in the hippocampus of MD rats. Density of cholinergic fibers was significantly increased in CA1 region of hippocampus and decreased in RS cortex. Our results indicate that MD causes long-term structure specific changes in the cholinergic system.

  13. Boosting the oxidase mimicking activity of nanoceria by fluoride capping: rivaling protein enzymes and ultrasensitive F(-) detection.

    Science.gov (United States)

    Liu, Biwu; Huang, Zhicheng; Liu, Juewen

    2016-07-14

    Nanomaterial-based enzyme mimics (nanozymes) are currently a new forefront of chemical research. However, the application of nanozymes is limited by their low catalytic activity and low turnover numbers. Cerium dioxide nanoparticles (nanoceria) are among the few with oxidase activity. Herein, we report an interesting finding addressing their limitations. The oxidase activity of nanoceria is improved by over 100-fold by fluoride capping, making it more close to real oxidases. The turnover number reached 700 in 15 min, drastically improved from ∼15 turnovers for the naked particles. The mechanism is attributed to surface charge modulation and facilitated electron transfer by F(-) capping based on ζ-potential and free radical measurements. Ultrasensitive sensing of fluoride was achieved with a detection limit of 0.64 μM F(-) in water and in toothpastes, while no other tested anions can achieve the activity enhancement. PMID:27378306

  14. Boosting the oxidase mimicking activity of nanoceria by fluoride capping: rivaling protein enzymes and ultrasensitive F- detection

    Science.gov (United States)

    Liu, Biwu; Huang, Zhicheng; Liu, Juewen

    2016-07-01

    Nanomaterial-based enzyme mimics (nanozymes) are currently a new forefront of chemical research. However, the application of nanozymes is limited by their low catalytic activity and low turnover numbers. Cerium dioxide nanoparticles (nanoceria) are among the few with oxidase activity. Herein, we report an interesting finding addressing their limitations. The oxidase activity of nanoceria is improved by over 100-fold by fluoride capping, making it more close to real oxidases. The turnover number reached 700 in 15 min, drastically improved from ~15 turnovers for the naked particles. The mechanism is attributed to surface charge modulation and facilitated electron transfer by F- capping based on ζ-potential and free radical measurements. Ultrasensitive sensing of fluoride was achieved with a detection limit of 0.64 μM F- in water and in toothpastes, while no other tested anions can achieve the activity enhancement.Nanomaterial-based enzyme mimics (nanozymes) are currently a new forefront of chemical research. However, the application of nanozymes is limited by their low catalytic activity and low turnover numbers. Cerium dioxide nanoparticles (nanoceria) are among the few with oxidase activity. Herein, we report an interesting finding addressing their limitations. The oxidase activity of nanoceria is improved by over 100-fold by fluoride capping, making it more close to real oxidases. The turnover number reached 700 in 15 min, drastically improved from ~15 turnovers for the naked particles. The mechanism is attributed to surface charge modulation and facilitated electron transfer by F- capping based on ζ-potential and free radical measurements. Ultrasensitive sensing of fluoride was achieved with a detection limit of 0.64 μM F- in water and in toothpastes, while no other tested anions can achieve the activity enhancement. Electronic supplementary information (ESI) available: Methods, TMB oxidation kinetics and control experiments. See DOI: 10.1039/c6nr02730j

  15. A boost for KAON

    International Nuclear Information System (INIS)

    Earlier this year, a report by a specially-formed subcommittee of the US Nuclear Science Advisory Committee gave an important boost to the proposal to build a high intensity particle beam 'factory' at the Canadian TRIUMF laboratory in Vancouver. (orig./HSI).

  16. Posterior parietal cortex dynamically ranks topographic signals via cholinergic influence

    Directory of Open Access Journals (Sweden)

    John Broussard

    2012-06-01

    Full Text Available The hypothesis to be discussed in this review is that posterior parietal cortex is directly involved in selecting relevant stimuli and filtering irrelevant distractors. The posterior parietal cortex receives input from several sensory modalities and integrates them in part to direct the allocation of resources to optimize gains. In conjunction with prefrontal cortex, nucleus accumbens, and basal forebrain cholinergic nuclei, it comprises a network mediating sustained attentional performance. Numerous anatomical, neurophysiological, and lesion studies have substantiated the notion that the basic functions of the posterior parietal cortex are conserved from rodents to humans. One such function is the detection and selection of relevant stimuli necessary for making optimal choices or responses. The issues to be addressed here are how behaviorally relevant targets recruit oscillatory potentials and spiking activity of posterior parietal neurons compared to similar yet irrelevant stimuli. Further, the influence of cortical cholinergic input to posterior parietal cortex in learning and decision-making is also discussed. I propose that these neurophysiological correlates of attention are transmitted to frontal cortical areas contributing to the top down selection of stimuli in a timely manner.

  17. Pharmakologische Charakterisierung zentraler cholinerger Dysfunktionen in transgenen Mausmodellen

    OpenAIRE

    Mohr, Franziska

    2014-01-01

    Die cholinerge Dysfunktion steht in Zusammenhang mit der Ätiologie der Alzheimer-Krankheit (AD). Das Absterben cholinerger Neurone führt zu einer verminderten cholinergen Neurotransmission im Gehirn. Die Abnahme der Acetylcholinesterase-(AChE)-Aktivität und eine leichte Zunahme der Butyrylcholinesterase-(BChE)-Aktivität zählen zu den charakteristischen Merkmalen der AD. Acetylcholinesterase-Inhibitoren (AChEI) sollen Acetylcholin (ACh)-Konzentrationen im Gehirn steigern, um cholinerge Defizit...

  18. The Protective Effect of Electroacupuncturing Zusanli Points on Hemorrhagic Shock Rats through Cholinergic Anti-inflammatory Pathway

    Institute of Scientific and Technical Information of China (English)

    Zhao-Hui DU; Jian-Guo LI; Yan-Lin WANG; Zhou-Quan PENG; Xiao-Feng YE

    2005-01-01

    @@ 1 Introduction In conditions of circulatory shock, systemic inflammatory response (SIRS) plays a funda mental pathogenetic role, with activation of transcription nuclear factors(mainly NF- kB) and markedly increased production of cytokines (mainly TNF-a), which trigger the inflammatory cascade active ation. Recent research have identified a basic neural pathway that reflexively monitors and adjusts such response. It is through the rapid activation (in "real-time") of efferent vagus nerve fibres(the recentlyrecognized "brain cholinergic antiinflammatory pathway" ) [1].There are show that the rapid activation cholinergic antiinflammatory pathway can protect against the hemorrhagic shock[2,3].

  19. Gut-targeted immunonutrition boosting natural killer cell activity using Saccharomyces boulardii lysates in immuno-compromised healthy elderly subjects.

    Science.gov (United States)

    Naito, Yasuhiro; Marotta, Francesco; Kantah, Makoto K; Zerbinati, Nicola; Kushugulova, Almagul; Zhumadilov, Zhaxybay; Illuzzi, Nicola; Sapienza, Chiara; Takadanohara, Hiroshi; Kobayashi, Riyichi; Catanzaro, Roberto

    2014-04-01

    The aim of this study was to assess the immunomodulatory effect of KC-1317 (a symbiotic mixture containing Saccharomyces boulardii lysate in a cranberry, colostrum-derived lactoferrin, fragaria, and lactose mixture) supplementation in immune-compromised but otherwise healthy elderly subjects. A liquid formulation of KC-1317 was administered in a randomized controlled trial (RCT) fashion to healthy volunteers (65-79 years) previously selected for low natural killer (NK) cell activity, and this parameter was checked at the completion of the study. A significant improvement in NK cell activity of KC-1317 consumers was observed as compared to placebo at the end of 2 months. Although preliminary, these beneficial immune-modulatory effects of KC-1317 in aged individuals might indicate its employment within a wider age-management strategy. PMID:24059806

  20. Powerful partnering: engaging the best to do the most in courting new realms to boost physical activity.

    Science.gov (United States)

    Stefan, Maria Dennison

    2011-09-01

    The central thesis of the commentary is that expanding engagement between the public and private sector, especially in the area of physical activity, is needed and important. Powerful partnering offers the perspective that business is reframing its priorities, moving from short-term gain to long-term sustainability; and that business leaders are regarding the term 'survival of the fittest' not in terms of who is the most competitive and strongest, but who is the most collaborative and adaptable. The commentary stakes a position that global problems in the 21(st) century need both a left and right brain approach, where leadership and the worldview must be connected and collaborative rather than sharply delineated and disconnected. Through a series of examples, the commentary seeks to share how and why business is currently involved in physical activity partnering; and approaches and guidelines public health can consider to build the collaboration bridge. PMID:24803558

  1. Gut-Targeted Immunonutrition Boosting Natural Killer Cell Activity Using Saccharomyces boulardii Lysates in Immuno-Compromised Healthy Elderly Subjects

    OpenAIRE

    Naito, Yasuhiro; Marotta, Francesco; Kantah, Makoto K.; Zerbinati, Nicola; Kushugulova, Almagul; Zhumadilov, Zhaxybay; Illuzzi, Nicola; Sapienza, Chiara; Takadanohara, Hiroshi; Kobayashi, Riyichi; Catanzaro, Roberto

    2014-01-01

    The aim of this study was to assess the immunomodulatory effect of KC-1317 (a symbiotic mixture containing Saccharomyces boulardii lysate in a cranberry, colostrum-derived lactoferrin, fragaria, and lactose mixture) supplementation in immune-compromised but otherwise healthy elderly subjects. A liquid formulation of KC-1317 was administered in a randomized controlled trial (RCT) fashion to healthy volunteers (65–79 years) previously selected for low natural killer (NK) cell activity, and this...

  2. A Viral Vectored Prime-Boost Immunization Regime Targeting the Malaria Pfs25 Antigen Induces Transmission-Blocking Activity

    OpenAIRE

    Goodman, Anna L.; Blagborough, Andrew M.; Sumi Biswas; Yimin Wu; Hill, Adrian V.; Sinden, Robert E.; Draper, Simon J

    2011-01-01

    The ookinete surface protein Pfs25 is a macrogamete-to-ookinete/ookinete stage antigen of Plasmodium falciparum, capable of exerting high-level anti-malarial transmission-blocking activity following immunization with recombinant protein-in-adjuvant formulations. Here, this antigen was expressed in recombinant chimpanzee adenovirus 63 (ChAd63), human adenovirus serotype 5 (AdHu5) and modified vaccinia virus Ankara (MVA) viral vectored vaccines. Two immunizations were administered to mice in a ...

  3. Attentional Control of Gait and Falls: Is Cholinergic Dysfunction a Common Substrate in the Elderly and Parkinson’s Disease?

    Science.gov (United States)

    Pelosin, Elisa; Ogliastro, Carla; Lagravinese, Giovanna; Bonassi, Gaia; Mirelman, Anat; Hausdorff, Jeffrey M.; Abbruzzese, Giovanni; Avanzino, Laura

    2016-01-01

    The aim of this study was to address whether deficits in the central cholinergic activity may contribute to the increased difficulty to allocate attention during gait in the elderly with heightened risk of falls. We recruited 50 participants with a history of two or more falls (33 patients with Parkinson’s Disease and 17 older adults) and 14 non-fallers age-matched adults. Cholinergic activity was estimated by means of short latency afferent inhibition (SAI), a transcranial magnetic stimulation (TMS) technique that assesses an inhibitory circuit in the sensorimotor cortex and is regarded as a global marker of cholinergic function in the brain. Increased difficulty to allocate attention during gait was evaluated by measuring gait performance under single and dual-task conditions. Global cognition was also assessed. Results showed that SAI was reduced in patients with PD than in the older adults (fallers and non-fallers) and in older adults fallers with respect to non-fallers. Reduction in SAI indicates less inhibition i.e., less cholinergic activity. Gait speed was reduced in the dual task gait compared to normal gait only in our faller population and changes in gait speed under dual task significantly correlated with the mean value of SAI. This association remained significant after adjusting for cognitive status. These findings suggest that central cholinergic activity may be a predictor of change in gait characteristics under dual tasking in older adults and PD fallers independently of cognitive status.

  4. Expression of constitutively active erythropoietin receptor in pyramidal neurons of cortex and hippocampus boosts higher cognitive functions in mice

    Directory of Open Access Journals (Sweden)

    Hassouna Imam

    2011-04-01

    Full Text Available Abstract Background Erythropoietin (EPO and its receptor (EPOR are expressed in the developing brain and their transcription is upregulated in adult neurons and glia upon injury or neurodegeneration. We have shown neuroprotective effects and improved cognition in patients with neuropsychiatric diseases treated with EPO. However, the critical EPO targets in brain are unknown, and separation of direct and indirect effects has remained difficult, given the role of EPO in hematopoiesis and brain oxygen supply. Results Here we demonstrate that mice with transgenic expression of a constitutively active EPOR isoform (cEPOR in pyramidal neurons of cortex and hippocampus exhibit enhancement of spatial learning, cognitive flexibility, social memory, and attentional capacities, accompanied by increased impulsivity. Superior cognitive performance is associated with augmented long-term potentiation of cEPOR expressing neurons in hippocampal slices. Conclusions Active EPOR stimulates neuronal plasticity independent of any hematopoietic effects and in addition to its neuroprotective actions. This property of EPOR signaling should be exploited for defining novel strategies to therapeutically enhance cognitive performance in disease conditions.

  5. Basal Forebrain Cholinergic Deficits Reduce Glucose Metabolism and Function of Cholinergic and GABAergic Systems in the Cingulate Cortex

    OpenAIRE

    Jeong, Da Un; Oh, Jin Hwan; Lee, Ji Eun; Lee, Jihyeon; Cho, Zang Hee; Chang, Jin Woo; Chang, Won Seok

    2015-01-01

    Purpose Reduced brain glucose metabolism and basal forebrain cholinergic neuron degeneration are common features of Alzheimer's disease and have been correlated with memory function. Although regions representing glucose hypometabolism in patients with Alzheimer's disease are targets of cholinergic basal forebrain neurons, the interaction between cholinergic denervation and glucose hypometabolism is still unclear. The aim of the present study was to evaluate glucose metabolism changes caused ...

  6. Breast boost - why, how, when...?

    International Nuclear Information System (INIS)

    Background: Breast conservation management including tumorectomy or quadrantectomy and external beam radiotherapy with a dose of 45 to 50 Gy in the treatment of small breast carcinomas is generally accepted. The use of a radiation boost - in particular for specific subgroups - has not been clarified. With regard to the boost technique there is some controversy between groups emphasizing the value of electron boost treatment and groups pointing out the value of interstitial boost treatment. This controversy has become even more complicated as there is an increasing number of institutions reporting the use of HDR interstitial brachytherapy for boost treatment. The most critical issue with regard to interstitial HDR brachytherapy is the assumed serious long-term morbidity after a high single radiation dose as used in HDR-treatments. Methods and Results: This article gives a perspective and recommendations on some aspects of this issue (indication, timing, target volume, dose and dose rate). Conclusion: More information about the indication for a boost is to be expected from the EORTC trial 22881/10882. Careful selection of treatment procedures for specific subgroups of patients and refinement in surgical procedures and radiotherapy techniques may be useful in improving the clinical and cosmetic results in breast conservation therapy. Prospective trials comparing on the one hand different boost techniques and on the other hand particular morphologic criteria in treatments with boost and without boost are needed to give more detailed recommendations for boost indication and for boost techniques. (orig.)

  7. Diversity-Based Boosting Algorithm

    Directory of Open Access Journals (Sweden)

    Jafar A. Alzubi

    2016-05-01

    Full Text Available Boosting is a well known and efficient technique for constructing a classifier ensemble. An ensemble is built incrementally by altering the distribution of training data set and forcing learners to focus on misclassification errors. In this paper, an improvement to Boosting algorithm called DivBoosting algorithm is proposed and studied. Experiments on several data sets are conducted on both Boosting and DivBoosting. The experimental results show that DivBoosting is a promising method for ensemble pruning. We believe that it has many advantages over traditional boosting method because its mechanism is not solely based on selecting the most accurate base classifiers but also based on selecting the most diverse set of classifiers.

  8. Regulatory changes in presynaptic cholinergic function assessed in rapid autopsy material from patients with Alzheimer disease: Implications for etiology and therapy

    International Nuclear Information System (INIS)

    Brain regions from patients with or without Alzheimer disease (AD) were obtained within 2 hr of death and examined for indices of presynaptic cholinergic function. Consistent with loss of cholinergic projections, cerebral cortical areas involved in AD exhibited decreased choline acetyltransferase activity. However, remaining nerve terminals in these regions displayed marked up-regulation of synaptosomal high affinity [3H]choline uptake, a result indicative of relative cholinergic hyperactivity. As choline uptake is also rate-limiting in acetylcholine biosynthesis, these findings have implications for both therapy and identification of causes contributing to neuronal death in AD

  9. Boosting Support Vector Machines

    Directory of Open Access Journals (Sweden)

    Elkin Eduardo García Díaz

    2006-11-01

    Full Text Available En este artículo, se presenta un algoritmo de clasificación binaria basado en Support Vector Machines (Máquinas de Vectores de Soporte que combinado apropiadamente con técnicas de Boosting consigue un mejor desempeño en cuanto a tiempo de entrenamiento y conserva características similares de generalización con un modelo de igual complejidad pero de representación más compacta./ In this paper we present an algorithm of binary classification based on Support Vector Machines. It is combined with a modified Boosting algorithm. It run faster than the original SVM algorithm with a similar generalization error and equal complexity model but it has more compact representation.

  10. Analytic Boosted Boson Discrimination

    CERN Document Server

    Larkoski, Andrew J; Neill, Duff

    2015-01-01

    Observables which discriminate boosted topologies from massive QCD jets are of great importance for the success of the jet substructure program at the Large Hadron Collider. Such observables, while both widely and successfully used, have been studied almost exclusively with Monte Carlo simulations. In this paper we present the first all-orders factorization theorem for a two-prong discriminant based on a jet shape variable, $D_2$, valid for both signal and background jets. Our factorization theorem simultaneously describes the production of both collinear and soft subjets, and we introduce a novel zero-bin procedure to correctly describe the transition region between these limits. By proving an all orders factorization theorem, we enable a systematically improvable description, and allow for precision comparisons between data, Monte Carlo, and first principles QCD calculations for jet substructure observables. Using our factorization theorem, we present numerical results for the discrimination of a boosted $Z...

  11. Analytic boosted boson discrimination

    OpenAIRE

    Andrew J. Larkoski; Moult, Ian; Neill, Duff

    2015-01-01

    Observables which discriminate boosted topologies from massive QCD jets are of great importance for the success of the jet substructure program at the Large Hadron Collider. Such observables, while both widely and successfully used, have been studied almost exclusively with Monte Carlo simulations. In this paper we present the first all-orders factorization theorem for a two-prong discriminant based on a jet shape variable, $D_2$, valid for both signal and background jets. Our factorization t...

  12. SUSY using boosted techniques

    CERN Document Server

    Stark, Giordon; The ATLAS collaboration

    2016-01-01

    In this talk, I present a discussion of techniques used in supersymmetry searches in papers published by the ATLAS Collaboration from late Run 1 to early Run 2. The goal is to highlight concepts the analyses have in common, why/how they work, and possible SUSY searches that could benefit from boosted studies. Theoretical background will be provided for reference to encourage participants to explore in depth on their own time.

  13. StructBoost: Boosting Methods for Predicting Structured Output Variables.

    Science.gov (United States)

    Chunhua Shen; Guosheng Lin; van den Hengel, Anton

    2014-10-01

    Boosting is a method for learning a single accurate predictor by linearly combining a set of less accurate weak learners. Recently, structured learning has found many applications in computer vision. Inspired by structured support vector machines (SSVM), here we propose a new boosting algorithm for structured output prediction, which we refer to as StructBoost. StructBoost supports nonlinear structured learning by combining a set of weak structured learners. As SSVM generalizes SVM, our StructBoost generalizes standard boosting approaches such as AdaBoost, or LPBoost to structured learning. The resulting optimization problem of StructBoost is more challenging than SSVM in the sense that it may involve exponentially many variables and constraints. In contrast, for SSVM one usually has an exponential number of constraints and a cutting-plane method is used. In order to efficiently solve StructBoost, we formulate an equivalent 1-slack formulation and solve it using a combination of cutting planes and column generation. We show the versatility and usefulness of StructBoost on a range of problems such as optimizing the tree loss for hierarchical multi-class classification, optimizing the Pascal overlap criterion for robust visual tracking and learning conditional random field parameters for image segmentation. PMID:26352637

  14. Invasive versus noninvasive measurement of allergic and cholinergic airway responsiveness in mice

    Directory of Open Access Journals (Sweden)

    Hohlfeld Jens M

    2005-11-01

    Full Text Available Abstract Background This study seeks to compare the ability of repeatable invasive and noninvasive lung function methods to assess allergen-specific and cholinergic airway responsiveness (AR in intact, spontaneously breathing BALB/c mice. Methods Using noninvasive head-out body plethysmography and the decrease in tidal midexpiratory flow (EF50, we determined early AR (EAR to inhaled Aspergillus fumigatus antigens in conscious mice. These measurements were paralleled by invasive determination of pulmonary conductance (GL, dynamic compliance (Cdyn and EF50 in another group of anesthetized, orotracheally intubated mice. Results With both methods, allergic mice, sensitized and boosted with A. fumigatus, elicited allergen-specific EAR to A. fumigatus (p Conclusion We conclude that invasive and noninvasive pulmonary function tests are capable of detecting both allergen-specific and cholinergic AR in intact, allergic mice. The invasive determination of GL and Cdyn is superior in sensitivity, whereas the noninvasive EF50 method is particularly appropriate for quick and repeatable screening of respiratory function in large numbers of conscious mice.

  15. Brain cholinergic involvement during the rapid development of tolerance to morphine

    Science.gov (United States)

    Wahba, Z. Z.; Oriaku, E. T.; Soliman, S. F. A.

    1987-01-01

    The effect of repeated administration of morphine on the activities of the cholinergic enzymes, choline acetyltransferase (ChAT) and acetylcholinesterase (AChE), in specific brain regions were studied in rats treated with 10 mg/kg morphine for one or two days. Repeated administration of morphine was associated with a decline in the degree of analgesia produced and with a significant increase of AChE activity of the medulla oblongata. A single injection of morphine resulted in a significant decline in ChAT activity in the hypothalamus, cerebellum, and medulla oblongata regions. After two consecutive injections, no decline in ChAT was observed in these regions, while in the cerebral cortex the second administration elicited a significant decline. The results suggest that the development of tolerance to morphine may be mediated through changes in ChAT activity and lend support to the involvement of the central cholinergic system in narcotic tolerance.

  16. Cholinergic pesticides cause mushroom body neuronal inactivation in honeybees

    OpenAIRE

    Palmer, Mary J; Moffat, Christopher; Saranzewa, Nastja; Harvey, Jenni; Wright, Geraldine A.; Connolly, Christopher N.

    2013-01-01

    Pesticides that target cholinergic neurotransmission are highly effective, but their use has been implicated in insect pollinator population decline. Honeybees are exposed to two widely used classes of cholinergic pesticide: neonicotinoids (nicotinic receptor agonists) and organophosphate miticides (acetylcholinesterase inhibitors). Although sublethal levels of neonicotinoids are known to disrupt honeybee learning and behaviour, the neurophysiological basis of these effects has not been shown...

  17. Stress-induced altered cholinergic-glutamatergic interactions in the mouse hippocampus.

    Science.gov (United States)

    Pavlovsky, Lev; Bitan, Yifat; Shalev, Hadar; Serlin, Yonatan; Friedman, Alon

    2012-09-01

    Psychological stress may lead to long-lasting brain dysfunction, specifically altered emotional and cognitive capabilities. Previous studies have demonstrated persistent changes in the expression of key cholinergic genes in the neocortex and hippocampus following stress with muscarinic receptor-mediated enhanced excitability. In the present study we examined cholinergic-mediated glutamatergic transmission in the hippocampus of mice after exposure to stress and its potential role in synaptic plasticity and altered behavior. Adult male mice were tested one month after repeated forced swimming test. Non-treated age-matched animals served as controls. Electrophysiological recordings were performed in the acute in-vitro slice preparation. CA1 pyramidal neurons were recorded using whole cell patch configuration. Extracellular recordings were done in response to Shaffer collaterals (SC) or stratum orien (SO) stimulation. Animal behavior in response to inhibition of acetylcholinesterase (AChE) was tested in open field paradigms. In whole cell patch recordings the frequency of excitatory post-synaptic currents (EPSCs) was significantly increased in response to muscarinic activation in stress-exposed animals. This enhanced cholinergic-modulated excitatory transmission is associated with facilitation of long-term potentiation (LTP) in response to tetanic stimulation at the SO but not at the SC. Stress-related behavioral modulation via central cholinergic pathways was enhanced by the central AChE inhibitor, physostigmine, thus further supporting the notion that stress is associated with long lasting hypersensitivity to acetylcholine. Our results revealed a pathway-specific enhancement of cholinergic-dependent glutamatergic transmission in the hippocampus after stress. These changes may underlie specific hippocampal malfunction, including cognitive and emotional disturbances, as observed in patients with post-traumatic stress disorder (PTSD). PMID:22796599

  18. Keap1 silencing boosts lipopolysaccharide-induced transcription of interleukin 6 via activation of nuclear factor κB in macrophages

    Energy Technology Data Exchange (ETDEWEB)

    Lv, Peng [Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); Institute for Chemical Safety Sciences, The Hamner Institutes for Health Sciences, 6 Davis Drive, Research Triangle Park, NC 27709 (United States); Xue, Peng; Dong, Jian [Institute for Chemical Safety Sciences, The Hamner Institutes for Health Sciences, 6 Davis Drive, Research Triangle Park, NC 27709 (United States); Peng, Hui [Institute for Chemical Safety Sciences, The Hamner Institutes for Health Sciences, 6 Davis Drive, Research Triangle Park, NC 27709 (United States); Evaluation and Research Center for Toxicology, Institute of Disease Control and Prevention, Academy of Military Medical Sciences (China); Clewell, Rebecca [Institute for Chemical Safety Sciences, The Hamner Institutes for Health Sciences, 6 Davis Drive, Research Triangle Park, NC 27709 (United States); Wang, Aiping [Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); Wang, Yue [Institute for Medical Device Standardization Administration, National Institutes for Food and Drug Control, Beijing (China); Peng, Shuangqing [Evaluation and Research Center for Toxicology, Institute of Disease Control and Prevention, Academy of Military Medical Sciences (China); Qu, Weidong [Key Laboratory of the Public Health Safety, Ministry of Education, School of Public Health, Fudan University, Shanghai (China); Zhang, Qiang; Andersen, Melvin E. [Institute for Chemical Safety Sciences, The Hamner Institutes for Health Sciences, 6 Davis Drive, Research Triangle Park, NC 27709 (United States); Pi, Jingbo, E-mail: jpi@thehamner.org [Institute for Chemical Safety Sciences, The Hamner Institutes for Health Sciences, 6 Davis Drive, Research Triangle Park, NC 27709 (United States)

    2013-11-01

    Interleukin-6 (IL6) is a multifunctional cytokine that regulates immune and inflammatory responses. Multiple transcription factors, including nuclear factor κB (NF-κB) and nuclear factor E2-related factor 2 (Nrf2), regulate IL6 transcription. Kelch-like ECH-associated protein 1 (Keap1) is a substrate adaptor protein for the Cullin 3-dependent E3 ubiquitin ligase complex, which regulates the degradation of many proteins, including Nrf2 and IκB kinase β (IKKβ). Here, we found that stable knockdown of Keap1 (Keap1-KD) in RAW 264.7 (RAW) mouse macrophages and human monocyte THP-1 cells significantly increased expression of Il6, and Nrf2-target genes, under basal and lipopolysaccharide (LPS, 0.001–0.1 μg/ml)-challenged conditions. However, Nrf2 activation alone, by tert-butylhydroquinone treatment of RAW cells, did not increase expression of Il6. Compared to cells transduced with scrambled non-target negative control shRNA, Keap1-KD RAW cells showed enhanced protein levels of IKKβ and increased expression and phosphorylation of NF-κB p65 under non-stressed and LPS-treated conditions. Because the expression of Il6 in Keap1-KD RAW cells was significantly attenuated by silencing of Ikkβ, but not Nrf2, it appears that stabilized IKKβ is responsible for the enhanced transactivation of Il6 in Keap1-KD cells. This study demonstrated that silencing of Keap1 in macrophages boosts LPS-induced transcription of Il6 via NF-κB activation. Given the importance of IL6 in the inflammatory response, the Keap1–IKKβ–NF-κB pathway may be a novel target for treatment and prevention of inflammation and associated disorders. - Highlights: • Knockdown of Keap1 increases expression of Il6 in macrophages. • Silencing of Keap1 results in protein accumulation of IKKβ and NF-κB p65. • Induction of Il6 resulting from Keap1 silencing is attributed to NF-κB activation.

  19. Impaired Cholinergic Excitation of Prefrontal Attention Circuitry in the TgCRND8 Model of Alzheimer’s Disease

    Science.gov (United States)

    Proulx, Éliane; Fraser, Paul; McLaurin, JoAnne; Lambe, Evelyn K.

    2015-01-01

    Attention deficits in Alzheimer’s disease can exacerbate its other cognitive symptoms, yet relevant disruptions of key prefrontal circuitry are not well understood. Here, in the TgCRND8 mouse model of this neurological disorder, we demonstrate and characterize a disruption of cholinergic excitation in the major corticothalamic layer of the prefrontal cortex, in which modulation by acetylcholine is essential for optimal attentional function. Using electrophysiology with concurrent multiphoton imaging, we show that layer 6 pyramidal cells are unable to sustain cholinergic excitation to the same extent as their nontransgenic littermate controls, as a result of the excessive activation of calcium-activated hyperpolarizing conductances. We report that cholinergic excitation can be improved in TgCRND8 cortex by pharmacological blockade of SK channels, suggesting a novel target for the treatment of cognitive dysfunction in Alzheimer’s disease. PMID:26377466

  20. Cholinergic Mechanisms in the Cerebral Cortex: Beyond Synaptic Transmission.

    Science.gov (United States)

    Ovsepian, Saak V; O'Leary, Valerie B; Zaborszky, Laszlo

    2016-06-01

    Functional overviews of cholinergic mechanisms in the cerebral cortex have traditionally focused on the release of acetylcholine with modulator and transmitter effects. Recently, however, data have emerged that extend the role of acetylcholine and cholinergic innervations to a range of housekeeping and metabolic functions. These include regulation of amyloid precursor protein (APP) processing with production of amyloid β (Aβ) and other APP fragments and control of the phosphorylation of microtubule-associated protein (MAP) tau. Evidence has been also presented for receptor-ligand like interactions of cholinergic receptors with soluble Aβ peptide and MAP tau, with modulator and signaling effects. Moreover, high-affinity binding of Aβ to the neurotrophin receptor p75 (p75NTR) enriched in basalo-cortical cholinergic projections has been implicated in clearance of Aβ and nucleation of amyloid plaques. Here, we critically evaluate these unorthodox cholinergic mechanisms and discuss their role in neuronal physiology and the biology of Alzheimer's disease. PMID:26002948

  1. Cholinergic vasodilator mechanism in human fingers

    International Nuclear Information System (INIS)

    The effect of a cholinergic agonist and antagonist on finger blood flow (FBF) was studied in 10 normal subjects. Total finger blood flow was measured by venous occlusion, air plethysmography, and capillary blood flow (FCF) by the disappearance rate of a radio-isotope from a fingertip injection. Methacholine in doses of 10-80 μg/min was given by constant infusion via a brachial artery catheter. Average FBF and vascular resistance were not significantly affected. However, the half time (t/sub 1/2/) of the disappearance rate decreased from 50.8 +/- 13.4 to 11.1 +/- 1.5 min; a decrease occurred in all subjects. In seven subjects, atropine (0.2 mg) had no affect alone but inhibited the effect of methacholine on FCF and prevented the redness and sweating of the forearm and hand that occurs with this agent. This study demonstrates a muscarinic cholinergic vasodilator mechanism in the fingertip that uniquely increase capillary blood flow

  2. Cholinergic vasodilator mechanism in human fingers

    Energy Technology Data Exchange (ETDEWEB)

    Coffman, J.D.; Cohen, R.A.

    1987-03-01

    The effect of a cholinergic agonist and antagonist on finger blood flow (FBF) was studied in 10 normal subjects. Total finger blood flow was measured by venous occlusion, air plethysmography, and capillary blood flow (FCF) by the disappearance rate of a radio-isotope from a fingertip injection. Methacholine in doses of 10-80 ..mu..g/min was given by constant infusion via a brachial artery catheter. Average FBF and vascular resistance were not significantly affected. However, the half time (t/sub 1/2/) of the disappearance rate decreased from 50.8 +/- 13.4 to 11.1 +/- 1.5 min; a decrease occurred in all subjects. In seven subjects, atropine (0.2 mg) had no affect alone but inhibited the effect of methacholine on FCF and prevented the redness and sweating of the forearm and hand that occurs with this agent. This study demonstrates a muscarinic cholinergic vasodilator mechanism in the fingertip that uniquely increase capillary blood flow.

  3. Boost C++ application development cookbook

    CERN Document Server

    Polukhin, Antony

    2013-01-01

    This book follows a cookbook approach, with detailed and practical recipes that use Boost libraries.This book is great for developers new to Boost, and who are looking to improve their knowledge of Boost and see some undocumented details or tricks. It's assumed that you will have some experience in C++ already, as well being familiar with the basics of STL. A few chapters will require some previous knowledge of multithreading and networking. You are expected to have at least one good C++ compiler and compiled version of Boost (1.53.0 or later is recommended), which will be used during the exer

  4. Gradient boosting machines, a tutorial.

    Science.gov (United States)

    Natekin, Alexey; Knoll, Alois

    2013-01-01

    Gradient boosting machines are a family of powerful machine-learning techniques that have shown considerable success in a wide range of practical applications. They are highly customizable to the particular needs of the application, like being learned with respect to different loss functions. This article gives a tutorial introduction into the methodology of gradient boosting methods with a strong focus on machine learning aspects of modeling. A theoretical information is complemented with descriptive examples and illustrations which cover all the stages of the gradient boosting model design. Considerations on handling the model complexity are discussed. Three practical examples of gradient boosting applications are presented and comprehensively analyzed. PMID:24409142

  5. Gradient Boosting Machines, A Tutorial

    Directory of Open Access Journals (Sweden)

    Alexey eNatekin

    2013-12-01

    Full Text Available Gradient boosting machines are a family of powerful machine-learning techniques that have shown considerable success in a wide range of practical applications. They are highly customizable to the particular needs of the application, like being learned with respect to different loss functions. This article gives a tutorial introduction into the methodology of gradient boosting methods. A theoretical information is complemented with many descriptive examples and illustrations which cover all the stages of the gradient boosting model design. Considerations on handling the model complexity are discussed. A set of practical examples of gradient boosting applications are presented and comprehensively analyzed.

  6. Properties of cholinergic and non-cholinergic submucosal neurons along the mouse colon.

    Science.gov (United States)

    Foong, Jaime Pei Pei; Tough, Iain R; Cox, Helen M; Bornstein, Joel C

    2014-02-15

    Submucosal neurons are vital regulators of water and electrolyte secretion and local blood flow in the gut. Due to the availability of transgenic models for enteric neuropathies, the mouse has emerged as the research model of choice, but much is still unknown about the murine submucosal plexus. The progeny of choline acetyltransferase (ChAT)-Cre × ROSA26(YFP) reporter mice, ChAT-Cre;R26R-yellow fluorescent protein (YFP) mice, express YFP in every neuron that has ever expressed ChAT. With the aid of the robust YFP staining in these mice, we correlated the neurochemistry, morphology and electrophysiology of submucosal neurons in distal colon. We also examined whether there are differences in neurochemistry along the colon and in neurally mediated vectorial ion transport between the proximal and distal colon. All YFP(+) submucosal neurons also contained ChAT. Two main neurochemical but not electrophysiological groups of neurons were identified: cholinergic (containing ChAT) or non-cholinergic. The vast majority of neurons in the middle and distal colon were non-cholinergic but contained vasoactive intestinal peptide. In the distal colon, non-cholinergic neurons had one or two axons, whereas the cholinergic neurons examined had only one axon. All submucosal neurons exhibited S-type electrophysiology, shown by the lack of long after-hyperpolarizing potentials following their action potentials and fast excitatory postsynaptic potentials (EPSPs). Fast EPSPs were predominantly nicotinic, and somatic action potentials were mediated by tetrodotoxin-resistant voltage-gated channels. The size of submucosal ganglia decreased but the proportion of cholinergic neurons increased distally along the colon. The distal colon had a significantly larger nicotinic ion transport response than the proximal colon. This work shows that the properties of murine submucosal neurons and their control of epithelial ion transport differ between colonic regions. There are several key differences

  7. Analytic boosted boson discrimination

    Science.gov (United States)

    Larkoski, Andrew J.; Moult, Ian; Neill, Duff

    2016-05-01

    Observables which discriminate boosted topologies from massive QCD jets are of great importance for the success of the jet substructure program at the Large Hadron Collider. Such observables, while both widely and successfully used, have been studied almost exclusively with Monte Carlo simulations. In this paper we present the first all-orders factorization theorem for a two-prong discriminant based on a jet shape variable, D 2, valid for both signal and background jets. Our factorization theorem simultaneously describes the production of both collinear and soft subjets, and we introduce a novel zero-bin procedure to correctly describe the transition region between these limits. By proving an all orders factorization theorem, we enable a systematically improvable description, and allow for precision comparisons between data, Monte Carlo, and first principles QCD calculations for jet substructure observables. Using our factorization theorem, we present numerical results for the discrimination of a boosted Z boson from massive QCD background jets. We compare our results with Monte Carlo predictions which allows for a detailed understanding of the extent to which these generators accurately describe the formation of two-prong QCD jets, and informs their usage in substructure analyses. Our calculation also provides considerable insight into the discrimination power and calculability of jet substructure observables in general.

  8. Gut feeling: MicroRNA discriminators of the intestinal TLR9-cholinergic links.

    Science.gov (United States)

    Nadorp, Bettina; Soreq, Hermona

    2015-11-01

    The intestinal tissue notably responds to stressful, cholinergic and innate immune signals by microRNA (miRNA) changes, but whether and how those miRNA regulators modify the intestinal cholinergic and innate immune pathways remained unexplored. Here, we report changes in several miRNA regulators of cholinesterases (ChEs) and correspondingly modified ChE activities in intestine, splenocytes and the circulation of mice exposed to both stress and canonical or alternative Toll-Like Receptor 9 (TLR9) oligonucleotide (ODN) aptamer activators or blockers. Stressful intraperitoneal injection of saline, the anti-inflammatory TLR9 agonist mEN101 aptamer or the inflammation-activating TLR9 aptamer ODN 1826 all increased the expression of the acetylcholinesterase (AChE)-targeting miR-132. In comparison, mEN101 but neither ODN 1826 nor saline injections elevated intestinal miR-129-5p, miR-186 and miR-200c, all predicted to target both AChE and the homologous enzyme butyrylcholinesterase (BChE). In cultured immune cells, BL-7040, the human counterpart of mEN101, reduced AChE activity reflecting inflammatory reactions in a manner preventable by the TLR9 blocking ODN 2088. Furthermore, the anti-inflammatory BL-7040 TLR9 aptamer caused reduction in nitric oxide and AChE activity in both murine splenocytes and human mononuclear cells at molar concentrations four orders of magnitude lower than ODN 1826. Our findings demonstrate differential reaction of cholinesterase-targeting miRNAs to distinct TLR9 challenges, indicating upstream miRNA co-regulation of the intestinal alternative NFκB pathway and cholinergic signaling. TLR9 aptamers may hence potentiate miRNA regulation that enhances cholinergic signaling and the resolution of inflammation, which opens new venues for manipulating bowel diseases. PMID:26003847

  9. Testosterone Therapy May Boost Older Men's Sex Lives

    Science.gov (United States)

    ... 159622.html Testosterone Therapy May Boost Older Men's Sex Lives Gel hormone treatment led to improved libido ... experienced a moderate but significant improvement in their sex drive, sexual activity and erectile function compared to ...

  10. Prime-Boost Vaccination Using Chemokine-Fused gp120 DNA and HIV Envelope Peptides Activates Both Immediate and Long-Term Memory Cellular Responses in Rhesus Macaques

    Directory of Open Access Journals (Sweden)

    Hong Qin

    2010-01-01

    Full Text Available HIV vaccine candidates with improved immunogenicity and induction of mucosal T-cell immunity are needed. A prime-boost strategy using a novel HIV glycoprotein 120 DNA vaccine was employed to immunize rhesus macaques. The DNA vaccine encoded a chimeric gp120 protein in fusion with monocyte chemoattractant protein-3, which was hypothesized to improve the ability of antigen-presenting cells to capture viral antigen through chemokine receptor-mediated endocytosis. DNA vaccination induced virus-reactive T cells in peripheral blood, detectable by T cell proliferation, INFγ ELISPOT and sustained IL-6 production, without humoral responses. With a peptide-cocktail vaccine containing a set of conserved polypeptides of HIV-1 envelope protein, given by nasogastric administration, primed T-cell immunity was significantly boosted. Surprisingly, long-term and peptide-specific mucosal memory T-cell immunity was detected in both vaccinated macaques after one year. Therefore, data from this investigation offer proof-of-principle for potential effectiveness of the prime-boost strategy with a chemokine-fused gp120 DNA and warrant further testing in the nonhuman primate models for developing as a potential HIV vaccine candidate in humans.

  11. Neurostimulation of the cholinergic anti-inflammatory pathway ameliorates disease in rat collagen-induced arthritis.

    Directory of Open Access Journals (Sweden)

    Yaakov A Levine

    Full Text Available INTRODUCTION: The inflammatory reflex is a physiological mechanism through which the nervous system maintains immunologic homeostasis by modulating innate and adaptive immunity. We postulated that the reflex might be harnessed therapeutically to reduce pathological levels of inflammation in rheumatoid arthritis by activating its prototypical efferent arm, termed the cholinergic anti-inflammatory pathway. To explore this, we determined whether electrical neurostimulation of the cholinergic anti-inflammatory pathway reduced disease severity in the collagen-induced arthritis model. METHODS: Rats implanted with vagus nerve cuff electrodes had collagen-induced arthritis induced and were followed for 15 days. Animals underwent active or sham electrical stimulation once daily from day 9 through the conclusion of the study. Joint swelling, histology, and levels of cytokines and bone metabolism mediators were assessed. RESULTS: Compared with sham treatment, active neurostimulation of the cholinergic anti-inflammatory pathway resulted in a 52% reduction in ankle diameter (p = 0.02, a 57% reduction in ankle diameter (area under curve; p = 0.02 and 46% reduction overall histological arthritis score (p = 0.01 with significant improvements in inflammation, pannus formation, cartilage destruction, and bone erosion (p = 0.02, accompanied by numerical reductions in systemic cytokine levels, not reaching statistical significance. Bone erosion improvement was associated with a decrease in serum levels of receptor activator of NF-κB ligand (RANKL from 132±13 to 6±2 pg/mL (mean±SEM, p = 0.01. CONCLUSIONS: The severity of collagen-induced arthritis is reduced by neurostimulation of the cholinergic anti-inflammatory pathway delivered using an implanted electrical vagus nerve stimulation cuff electrode, and supports the rationale for testing this approach in human inflammatory disorders.

  12. Novel Fast Adapting Interneurons Mediate Cholinergic-Induced Fast GABAA IPSCs In Striatal Spiny Neurons

    OpenAIRE

    Faust, Thomas W.; Assous, Maxime; Shah, Fulva; Tepper, James M.; Koós, Tibor

    2015-01-01

    Previous work suggests that neostriatal cholinergic interneurons control the activity of several classes of GABAergic interneurons through fast nicotinic receptor mediated synaptic inputs. Although indirect evidence has suggested the existence of several classes of interneurons controlled by this mechanism only one such cell type, the neuropeptide-Y expressing neurogliaform neuron, has been identified to date. Here we tested the hypothesis that in addition to the neurogliaform neurons that el...

  13. Presenilin-1 Mutation Impairs Cholinergic Modulation of Synaptic Plasticity and Suppresses NMDA Currents in Hippocampus slices

    OpenAIRE

    Wang, Yue; Greig, Nigel H.; Yu, Qian-Sheng; Mattson, Mark P.

    2008-01-01

    Presenilin-1 (PS1) mutations cause many cases of early-onset inherited Alzheimer's disease, in part, by increasing the production of neurotoxic forms of amyloid β-peptide (A β). However, Aβ -independent effects of mutant PS1 on neuronal Ca2+ homeostasis and sensitivity to excitatory neurotransmitters have been reported. Here we show that cholinergic modulation of hippocampal synaptic plasticity is impaired in PS1 mutant knockin (PS1KI) mice. Whereas activation of muscarinic receptors enhances...

  14. Local cholinergic and non-cholinergic neural pathways to the rat supraoptic nucleus

    International Nuclear Information System (INIS)

    An estimated two thirds of the input to the supraoptic nucleus of the rat hypothalamus (SON) including a functionally significant cholinergic innervation, arise from local sources of unknown origin. The sources of these inputs were identified utilizing Golgi-Cox, retrograde tracing, choline acetyltransferase immunocytochemistry and anterograde tracing methodologies. Multipolar Golgi impregnated neurons located dorsal and lateral to the SON extend spiney processes into the nucleus. Injections of the retrograde tracers, wheat germ agglutinin or wheat germ agglutinin-horseradish peroxidase, into the SON labeled cells bilaterally in the arcuate nucleus, and ipsilaterally in the lateral hypothalamus, anterior hypothalamus, nucleus of the diagonal band, subfornical organ, medial preoptic area, lateral preoptic area and in the region dorsolateral to the nucleus. Immunocytochemistry for choline acetyltransferase revealed cells within the ventro-caudal portion of cholinergic cell group, Ch4, which cluster dorsolateral to the SON, and extend axon- and dendrite-like processes into the SON. Cells double-labeled by choline acetyltransferase immunocytochemistry and retrograde tracer injections into the SON are localized within the same cholinergic cell group dorsolateral to the SON. Injections of the anterograde tracer, Phaseolus vulgaris-leucoagglutinin, deposited dorsolateral to the SON results in labeled pre-and post-synaptic processes within the SON. The identification and characterization of endogenous immunoglobulin within the SON and other neurons innervating areas lacking a blood-brain barrier established a novel and potentially important system for direct communication of the supraoptic cells with blood-borne constitutents

  15. Ultrarelativistic boost with scalar field

    Science.gov (United States)

    Svítek, O.; Tahamtan, T.

    2016-02-01

    We present the ultrarelativistic boost of the general global monopole solution which is parametrized by mass and deficit solid angle. The problem is addressed from two different perspectives. In the first one the primary object for performing the boost is the metric tensor while in the second one the energy momentum tensor is used. Since the solution is sourced by a triplet of scalar fields that effectively vanish in the boosting limit we investigate the behavior of a scalar field in a simpler setup. Namely, we perform the boosting study of the spherically symmetric solution with a free scalar field given by Janis, Newman and Winicour. The scalar field is again vanishing in the limit pointing to a broader pattern of scalar field behaviour during an ultrarelativistic boost in highly symmetric situations.

  16. Effects of diazinon on the lymphocytic cholinergic system of Nile tilapia fish (Oreochromis niloticus).

    Science.gov (United States)

    Toledo-Ibarra, G A; Díaz-Resendiz, K J G; Pavón-Romero, L; Rojas-García, A E; Medina-Díaz, I M; Girón-Pérez, M I

    2016-08-01

    Fish rearing under intensive farming conditions can be easily disturbed by pesticides, substances that have immunotoxic properties and may predispose to infections. Organophosphorus pesticides (OPs) are widely used in agricultural activities; however, the mechanism of immunotoxicity of these substances is unclear. The aim of this study was to evaluate the effect of diazinon pesticides (OPs) on the cholinergic system of immune cells as a possible target of OP immunotoxicity. We evaluated ACh levels and cholinergic (nicotinic and muscarinic) receptor concentration. Additionally, AChE activity was evaluated in mononuclear cells of Nile tilapia (Oreochromis niloticus), a freshwater fish mostly cultivated in tropical regions around the world. The obtained results indicate that acute exposure to diazinon induces an increase in ACh concentration and a decrease in nAChR and mAChR concentrations and AChE activity in fish immune cells, This suggests that the non-neuronal lymphocytic cholinergic system may be the main target in the mechanism of OP immunotoxicity. This study contributes to the understanding of the mechanisms of immunotoxicity of pollutants and may help to take actions for animal health improvement. PMID:27260186

  17. Chronic administration of sulbutiamine improves long term memory formation in mice: possible cholinergic mediation.

    Science.gov (United States)

    Micheau, J; Durkin, T P; Destrade, C; Rolland, Y; Jaffard, R

    1985-08-01

    Thiamine deficiency in both man and animals is known to produce memory dysfunction and cognitive disorders which have been related to an impairment of cholinergic activity. The present experiment was aimed at testing whether, inversely, chronic administration of large doses of sulbutiamine would have a facilitative effect on memory and would induce changes in central cholinergic activity. Accordingly mice received 300 mg/kg of sulbutiamine daily for 10 days. They were then submitted to an appetitive operant level press conditioning test. When compared to control subjects, sulbutiamine treated mice learned the task at the same rate in a single session but showed greatly improved performance when tested 24 hr after partial acquisition of the same task. Parallel neurochemical investigations showed that the treatment induced a slight (+ 10%) but significant increase in hippocampal sodium-dependent high affinity choline uptake. The present findings and previous results suggest that sulbutiamine improves memory formation and that this behavioral effect could be mediated by an increase in hippocampal cholinergic activity. PMID:4059305

  18. Boosted Higgs channels

    International Nuclear Information System (INIS)

    In gluon fusion both a modified top Yukawa and new colored particles can alter the cross section. However in a large set of composite Higgs models and in realistic areas of the MSSM parameter space, these two effects can conspire and hide new physics in a Standard Model-like inclusive cross section. We first show that it is possible to break this degeneracy in the couplings by demanding a boosted Higgs recoiling against a high-pT jet. Subsequently we propose an analysis based on this idea in the H→2l+ET channels. This measurement allows an alternative determination of the important top Yukawa besides the t anti tH channel.

  19. Boosted Higgs shapes

    International Nuclear Information System (INIS)

    The inclusive Higgs production rate through gluon fusion has been measured to be in agreement with the Standard Model (SM). We show that even if the inclusive Higgs production rate is very SM-like, a precise determination of the boosted Higgs transverse momentum shape offers the opportunity to see effects of natural new physics. These measurements are generically motivated by effective field theory arguments and specifically in extensions of the SM with a natural weak scale, like composite Higgs models and natural supersymmetry. We show in detail how a measurement at high transverse momentum of H→2l+pT via H→ττ and H→WW* could be performed and demonstrate that it offers a compelling alternative to the t anti tH channel. We discuss the sensitivity to new physics in the most challenging scenario of an exactly SM-like inclusive Higgs cross-section.

  20. Detection of Illegitimate Emails using Boosting Algorithm

    DEFF Research Database (Denmark)

    Nizamani, Sarwat; Memon, Nasrullah; Wiil, Uffe Kock

    2011-01-01

    spam email detection. For our desired task, we have applied a boosting technique. With the use of boosting we can achieve high accuracy of traditional classification algorithms. When using boosting one has to choose a suitable weak learner as well as the number of boosting iterations. In this paper, we...... propose a Naive Bayes classifier as a suitable weak learner for the boosting algorithm. It achieves maximum performance with very few boosting iterations....

  1. A kinetic model for the frequency dependence of cholinergic modulation at hippocampal GABAergic synapses.

    Science.gov (United States)

    Stone, Emily; Haario, Heikki; Lawrence, J Josh

    2014-12-01

    In this paper we use a simple model of presynaptic neuromodulation of GABA signaling to decipher paired whole-cell recordings of frequency dependent cholinergic neuromodulation at CA1 parvalbumin-containing basket cell (PV BC)-pyramidal cell synapses. Variance-mean analysis is employed to normalize the data, which is then used to estimate parameters in the mathematical model. Various parameterizations and hidden parameter dependencies are investigated using Markov Chain Monte Carlo (MCMC) parameter estimation techniques. This analysis reveals that frequency dependence of cholinergic modulation requires both calcium-dependent recovery from depression and mAChR-induced inhibition of presynaptic calcium entry. A reduction in calcium entry into the presynaptic terminal in the kinetic model accounted for the frequency-dependent effects of mAChR activation. PMID:25445738

  2. Protective role of the cholinergic anti-inflammatory pathway in a mouse model of viral myocarditis.

    Directory of Open Access Journals (Sweden)

    Zheng Cheng

    Full Text Available Activation of the cholinergic anti-inflammatory pathway, which relies on the α7nAchR (alpha 7 nicotinic acetylcholine receptor, has been shown to decrease proinflammatory cytokines. This relieves inflammatory responses and improves the prognosis of patients with experimental sepsis, endotoxemia, ischemia/reperfusion injury, hemorrhagic shock, pancreatitis, arthritis and other inflammatory syndromes. However, whether the cholinergic anti-inflammatory pathway has an effect on acute viral myocarditis has not been investigated. Here, we studied the effects of the cholinergic anti-inflammatory pathway on acute viral myocarditis.In a coxsackievirus B3 murine myocarditis model (Balb/c, nicotine and methyllycaconitine were used to stimulate and block the cholinergic anti-inflammatory pathway, respectively. Relevant signal pathways were studied to compare their effects on myocarditis, survival rate, histopathological changes, ultrastructural changes, and cytokine levels. Nicotine treatments significantly improved survival rate, attenuated myocardial lesions, and downregulated the expression of TNF-α and IL-6. Methyllycaconitine decreased survival rate, aggravated myocardial lesions, and upregulated the expression of TNF-α and IL-6. In addition, levels of the signaling protein phosphorylated STAT3 were higher in the nicotine group and lower in the methyllycaconitine group compared with the untreated myocarditis group.These results show that nicotine protects mice from CVB3-induced viral myocarditis and that methyllycaconitine aggravates viral myocarditis in mice. Because nicotine is a α7nAchR agonist and methyllycaconitine is a α7nAchR antagonist, we conclude that α7nAchR activation increases the phosphorylation of STAT3, reduces the expression of TNF-α and IL-6, and, ultimately, alleviates viral myocarditis. We also conclude that blocking α7nAchR reduces the phosphorylation of STAT3, increases the expression of TNF-α and IL-6, aggravating viral

  3. Unraveling the mechanism of neuroprotection of curcumin in arsenic induced cholinergic dysfunctions in rats

    Energy Technology Data Exchange (ETDEWEB)

    Srivastava, Pranay [CSIR-Indian Institute of Toxicology Research, Post Box 80, MG Marg, Lucknow 226 001 (India); Yadav, Rajesh S. [CSIR-Indian Institute of Toxicology Research, Post Box 80, MG Marg, Lucknow 226 001 (India); Department of Crimnology and Forensic Science, Harisingh Gour University, Sagar 470 003 (India); Chandravanshi, Lalit P.; Shukla, Rajendra K.; Dhuriya, Yogesh K.; Chauhan, Lalit K.S. [CSIR-Indian Institute of Toxicology Research, Post Box 80, MG Marg, Lucknow 226 001 (India); Dwivedi, Hari N. [Babu Banarasi Das University, BBD City, Faizabad Road, Lucknow 227 015 (India); Pant, Aditiya B. [CSIR-Indian Institute of Toxicology Research, Post Box 80, MG Marg, Lucknow 226 001 (India); Khanna, Vinay K., E-mail: vkkhanna1@gmail.com [CSIR-Indian Institute of Toxicology Research, Post Box 80, MG Marg, Lucknow 226 001 (India)

    2014-09-15

    Earlier, we found that arsenic induced cholinergic deficits in rat brain could be protected by curcumin. In continuation to this, the present study is focused to unravel the molecular mechanisms associated with the protective efficacy of curcumin in arsenic induced cholinergic deficits. Exposure to arsenic (20 mg/kg body weight, p.o) for 28 days in rats resulted to decrease the expression of CHRM2 receptor gene associated with mitochondrial dysfunctions as evident by decrease in the mitochondrial membrane potential, activity of mitochondrial complexes and enhanced apoptosis both in the frontal cortex and hippocampus in comparison to controls. The ultrastructural images of arsenic exposed rats, assessed by transmission electron microscope, exhibited loss of myelin sheath and distorted cristae in the mitochondria both in the frontal cortex and hippocampus as compared to controls. Simultaneous treatment with arsenic (20 mg/kg body weight, p.o) and curcumin (100 mg/kg body weight, p.o) for 28 days in rats was found to protect arsenic induced changes in the mitochondrial membrane potential and activity of mitochondrial complexes both in frontal cortex and hippocampus. Alterations in the expression of pro- and anti-apoptotic proteins and ultrastructural damage in the frontal cortex and hippocampus following arsenic exposure were also protected in rats simultaneously treated with arsenic and curcumin. The data of the present study reveal that curcumin could protect arsenic induced cholinergic deficits by modulating the expression of pro- and anti-apoptotic proteins in the brain. More interestingly, arsenic induced functional and ultrastructural changes in the brain mitochondria were also protected by curcumin. - Highlights: • Neuroprotective mechanism of curcumin in arsenic induced cholinergic deficits studied • Curcumin protected arsenic induced enhanced expression of stress markers in rat brain • Arsenic compromised mitochondrial electron transport chain protected

  4. Unraveling the mechanism of neuroprotection of curcumin in arsenic induced cholinergic dysfunctions in rats

    International Nuclear Information System (INIS)

    Earlier, we found that arsenic induced cholinergic deficits in rat brain could be protected by curcumin. In continuation to this, the present study is focused to unravel the molecular mechanisms associated with the protective efficacy of curcumin in arsenic induced cholinergic deficits. Exposure to arsenic (20 mg/kg body weight, p.o) for 28 days in rats resulted to decrease the expression of CHRM2 receptor gene associated with mitochondrial dysfunctions as evident by decrease in the mitochondrial membrane potential, activity of mitochondrial complexes and enhanced apoptosis both in the frontal cortex and hippocampus in comparison to controls. The ultrastructural images of arsenic exposed rats, assessed by transmission electron microscope, exhibited loss of myelin sheath and distorted cristae in the mitochondria both in the frontal cortex and hippocampus as compared to controls. Simultaneous treatment with arsenic (20 mg/kg body weight, p.o) and curcumin (100 mg/kg body weight, p.o) for 28 days in rats was found to protect arsenic induced changes in the mitochondrial membrane potential and activity of mitochondrial complexes both in frontal cortex and hippocampus. Alterations in the expression of pro- and anti-apoptotic proteins and ultrastructural damage in the frontal cortex and hippocampus following arsenic exposure were also protected in rats simultaneously treated with arsenic and curcumin. The data of the present study reveal that curcumin could protect arsenic induced cholinergic deficits by modulating the expression of pro- and anti-apoptotic proteins in the brain. More interestingly, arsenic induced functional and ultrastructural changes in the brain mitochondria were also protected by curcumin. - Highlights: • Neuroprotective mechanism of curcumin in arsenic induced cholinergic deficits studied • Curcumin protected arsenic induced enhanced expression of stress markers in rat brain • Arsenic compromised mitochondrial electron transport chain protected

  5. Effect of augmenting cholinergic function on gait and balance

    OpenAIRE

    Mancini, Martina; Fling, Brett W.; Gendreau, Anne; Lapidus, Jodi; Fay B. Horak; Chung, Kathy; Nutt, John G.

    2015-01-01

    Background Impaired mobility and falls are clinically important complications of Parkinson’s disease (PD) and a major detractor from quality of life for which there are limited therapies. Pathological, neuroimaging and clinical evidence suggest that degeneration of cholinergic systems may contribute to impairments of balance and gait in PD. The proposed trial will examine the effects of augmentation of the cholinergic system on balance and gait. Design The study is a single-site, proof of con...

  6. Do process innovations boost SMEs productivity growth?

    OpenAIRE

    Juan Antonio Máñez Castillejo; Amparo Sanchis Llopis; Sanchis Llopis, Juan A.; María Engracia. Rochina Barrachina

    2009-01-01

    In this paper we explore in depth the effect of process innovations on total factor productivity growth for small and medium enterprises (SMEs), taking into account the potential endogeneity problem that may be caused by self selection into these activities. First, we analyse whether the ex-ante most productive SMEs are those that start introducing process innovations; then, we test whether process innovations boost SMEs productivity growth using matching techniques to control for the possibi...

  7. Mangifera indica Fruit Extract Improves Memory Impairment, Cholinergic Dysfunction, and Oxidative Stress Damage in Animal Model of Mild Cognitive Impairment

    Directory of Open Access Journals (Sweden)

    Jintanaporn Wattanathorn

    2014-01-01

    Full Text Available To date, the effective preventive paradigm against mild cognitive impairment (MCI is required. Therefore, we aimed to determine whether Mangifera indica fruit extract, a substance possessing antioxidant and cognitive enhancing effects, could improve memory impairment, cholinergic dysfunction, and oxidative stress damage in animal model of mild cognitive impairment. Male Wistar rats, weighing 180–200 g, were orally given the extract at doses of 12.5, 50, and 200 mg·kg−1 BW for 2 weeks before and 1 week after the bilateral injection of AF64A (icv. At the end of study, spatial memory, cholinergic neurons density, MDA level, and the activities of SOD, CAT, and GSH-Px enzymes in hippocampus were determined. The results showed that all doses of extract could improve memory together with the decreased MDA level and the increased SOD and GSH-Px enzymes activities. The increased cholinergic neurons density in CA1 and CA3 of hippocampus was also observed in rats treated with the extract at doses of 50 and 200 mg·kg−1 BW. Therefore, our results suggested that M. indica, the potential protective agent against MCI, increased cholinergic function and the decreased oxidative stress which in turn enhanced memory. However, further researches are essential to elucidate the possible active ingredients and detail mechanism.

  8. Physics with boosted top quarks

    CERN Document Server

    Kuutmann, Elin Bergeaas

    2014-01-01

    The production at the LHC of boosted top quarks (top quarks with a transverse momentum that greatly exceeds their rest mass) is a promising process to search for phenomena beyond the Standard Model. In this contribution several examples are discussed of new techniques to reconstruct and identify (tag) the collimated decay topology of the boosted hadronic decays of top quarks. Boosted top reconstruction techniques have been utilized in searches for new physical phenomena. An overview is given of searches by ATLAS, CDF and CMS for heavy new particles decaying into a top and an anti-top quark, vector-like quarks and supersymmetric partners to the top quark.

  9. Amyloid-β depresses excitatory cholinergic synaptic transmission in Drosophila

    Institute of Scientific and Technical Information of China (English)

    Liqun Fang; Jingjing Duan; Dongzhi Ran; Zihao Fan; Ying Yan; Naya Huang; Huaiyu Gu; Yulan Zhu

    2012-01-01

    Objective Decline,disruption,or alterations of nicotinic cholinergic mechanisms contribute to cognitive dysfunctions like Alzheimer's disease (AD).Although amyloid-β (Aβ) aggregation is a pathological hallmark of AD,the mechanisms by which Aβ peptides modulate cholinergic synaptic transmission and memory loss remain obscure.This study was aimed to investigate the potential synaptic modulation by Aβ of the cholinergic synapses between olfactory receptor neurons and projection neurons (PNs) in the olfactory lobe of the fruit fly.Methods Cholinergic spontaneous and miniature excitatory postsynaptic current (mEPSC) were recorded with whole-cell patch clamp from PNs in Drosophila AD models expressing Aβ40,Aβ42,or Aβ42Arc peptides in neural tissue.Results In fly pupae (2 days before eclosion),overexpression of Aβ42 or Aβ42Arc,but not Aβ40,led to a significant decrease of mEPSC frequency,while overexpression of Aβ40,Aβ42,or Aβ42Arc had no significant effect on mEPSC amplitude.In contrast,Pavlovian olfactory associative learning and lifespan assays showed that both short-term memory and lifespan were decreased in the Drosophila models expressing Aβ40,Aβ42,or Aβ42Arc.Conclusion Both electrophysiological and behavioral results showed an effect of Aβ peptide on cholinergic synaptic transmission and suggest a possible mechanism by which Aβ peptides cause cholinergic neuron degeneration and the consequent memory loss.

  10. Three Phase High Power Quality Two- Stage Boost Rectifier

    OpenAIRE

    P.NAMMALVAR; S. ANNAPOORANI

    2012-01-01

    Three-phase two-stage boost rectifier with sinusoidal input current are presented and a novel topology with two active power devices is proposed. These contain a capacitor for pumping action in DC circuit. This gives twostage boost operation to obtain higher DC output voltage. The rectifier can be operated in the switch mode forpumping action and for forcing the input current to follow its sinusoidal reference independent of the working conditions. The results of the proposed rectifier are co...

  11. ROLE OF CHOLINERGIC SYSTEM ON THE CONSTRUCTION OF MEMORY AND ITS INTERACTION WITH DOPAMINERGIC SYSTEM

    Directory of Open Access Journals (Sweden)

    F. Z. Zangeneh

    2006-07-01

    Full Text Available The central cholinergic system has been associated with cognitive function and memory and acetylcholine plays an important role during the early stages of memory consolidation. In this study, after training mice were tested with one way active avoidance procedure and retention were tested at 4, 8, 12, 16 and 24 hours of training and compared with non-shocked mice, in which it took 24 hours, a suitable time for retention test. Low dose administration of arecoline and physostigmine pre-training, immediate post-training and before retrieval showed that muscarinic agonist arecoline can potentiated memory in post trained and retrieval phases and reversible cholinesterase inhibitor physostigmine potentiated memory only in retrieval phase. Scopolamine disrupted acetylcholine potentiation only in retrieval phase. In the second part of this study, the effect of dopaminergic system was investigated. Low dose of apomorphine and D2 agonist bromocriptine potentiated memory when administered immediately post-training, and D2 antagonist sulpiride impaired memory. When the cholinergic system was blocked by scopolamine immediately post-training, apomorphine and bromocriptine potentiated memory and sulpiride impaired it. In conclusion, these results suggest that, cholinergic system in retrieval phase is very critical and there was no interaction between the two systems in the post-training phase.

  12. Somatostatin inhibits cANP-mediated cholinergic transmission in the myenteric plexus

    International Nuclear Information System (INIS)

    The mechanism by which somatostatin acts to modulate cholinergic transmission is not clear. In this study the authors investigated the role of the adenosine 3',5'-cyclic monophosphate (cAMP) system in mediating cholinergic transmission in the guinea pig myenteric plexus and examined the ability of somatostatin to alter acetylcholine (ACh) release stimulated by various cAMP agonists. Forskolin, 8-bromo-cAMP, vasoactive intestinal peptide (VIP), and cholera toxin each stimulated the release of [3H]ACh in a dose-related manner. Addition of theophylline enhanced the release of [3H]ACh stimulated by these cAMP agonists. The observations suggest that cAMP may serve as a physiological mediator for ACh release from myenteric neurons. Somatostatin inhibited release of [3H]ACh evoked by various cAMP agonists in a dose-related manner. Pretreatment with pertussis toxin antagonized the inhibitory effect of somatostatin on the release of [3H]ACh evoked by forskolin, VIP, or cholera toxin but had no effect on the inhibitory action of somatostatin on the release of [3H]ACh evoked by 8-bromo-cAMP. This suggests that the principal mechanism by which somatostatin inhibits cAMP-mediated cholinergic transmission is via activation of the inhibitory regulatory protein (Ni subunit) of adenyalte cyclase

  13. Distribution-Specific Agnostic Boosting

    CERN Document Server

    Feldman, Vitaly

    2009-01-01

    We consider the problem of boosting the accuracy of weak learning algorithms in the agnostic learning framework of Haussler (1992) and Kearns et al. (1992). Known algorithms for this problem (Ben-David et al., 2001; Gavinsky, 2002; Kalai et al., 2008) follow the same strategy as boosting algorithms in the PAC model: the weak learner is executed on the same target function but over different distributions on the domain. We demonstrate boosting algorithms for the agnostic learning framework that only modify the distribution on the labels of the points (or, equivalently, modify the target function). This allows boosting a distribution-specific weak agnostic learner to a strong agnostic learner with respect to the same distribution. When applied to the weak agnostic parity learning algorithm of Goldreich and Levin (1989) our algorithm yields a simple PAC learning algorithm for DNF and an agnostic learning algorithm for decision trees over the uniform distribution using membership queries. These results substantia...

  14. Rosacea Might Boost Parkinson's Risk

    Science.gov (United States)

    ... medlineplus/news/fullstory_157883.html Rosacea Might Boost Parkinson's Risk: Study Research found an association, but did ... may be linked to an increased risk for Parkinson's disease, a large, new study suggests. Among more ...

  15. Subtle learning and memory impairment in an idiopathic rat model of Alzheimer's disease utilizing cholinergic depletions and β-amyloid.

    Science.gov (United States)

    Deibel, S H; Weishaupt, N; Regis, A M; Hong, N S; Keeley, R J; Balog, R J; Bye, C M; Himmler, S M; Whitehead, S N; McDonald, R J

    2016-09-01

    Alzheimer's disease (AD) is a disease of complex etiology, involving multiple risk factors. When these risk factors are presented concomitantly, cognition and brain pathology are more severely compromised than if those risk factors were presented in isolation. Reduced cholinergic tone and elevated amyloid-beta (Aβ) load are pathological hallmarks of AD. The present study sought to investigate brain pathology and alterations in learning and memory when these two factors were presented together in rats. Rats received either sham surgeries, cholinergic depletions of the medial septum, intracerebroventricular Aβ25-35 injections, or both cholinergic depletion and Aβ25-35 injections (Aβ+ACh group). The Aβ+ACh rats were unimpaired in a striatal dependent visual discrimination task, but had impaired acquisition in the standard version of the Morris water task. However, these rats displayed normal Morris water task retention and no impairment in acquisition of a novel platform location during a single massed training session. Aβ+ACh rats did not have exacerbated brain pathology as indicated by activated astroglia, activated microglia, or accumulation of Aβ. These data suggest that cholinergic depletions and Aβ injections elicit subtle cognitive deficits when behavioural testing is conducted shortly after the presentation of these factors. These factors might have altered hippocampal synaptic plasticity and thus resemble early AD pathology. PMID:27208489

  16. Gradient boosting machines, a tutorial

    OpenAIRE

    Natekin, Alexey; Knoll, Alois

    2013-01-01

    Gradient boosting machines are a family of powerful machine-learning techniques that have shown considerable success in a wide range of practical applications. They are highly customizable to the particular needs of the application, like being learned with respect to different loss functions. This article gives a tutorial introduction into the methodology of gradient boosting methods with a strong focus on machine learning aspects of modeling. A theoretical information is complemented with de...

  17. Gradient Boosting Machines, A Tutorial

    OpenAIRE

    Alexey Natekin; Alois Knoll

    2013-01-01

    Gradient boosting machines are a family of powerful machine-learning techniques that have shown considerable success in a wide range of practical applications. They are highly customizable to the particular needs of the application, like being learned with respect to different loss functions. This article gives a tutorial introduction into the methodology of gradient boosting methods. A theoretical information is complemented with many descriptive examples and illustrations which cover all th...

  18. Striatal cholinergic interneuron regulation and circuit effects

    Directory of Open Access Journals (Sweden)

    Sean Austin Lim

    2014-10-01

    Full Text Available The striatum plays a central role in motor control and motor learning. Appropriate responses to environmental stimuli, including pursuit of reward or avoidance of aversive experience all require functional striatal circuits. These pathways integrate synaptic inputs from limbic and cortical regions including sensory, motor and motivational information to ultimately connect intention to action. Although many neurotransmitters participate in striatal circuitry, one critically important player is acetylcholine (ACh. Relative to other brain areas, the striatum contains exceptionally high levels of ACh, the enzymes that catalyze its synthesis and breakdown, as well as both nicotinic and muscarinic receptor types that mediate its postsynaptic effects. The principal source of striatal ACh is the cholinergic interneuron (ChI, which comprises only about 1-2% of all striatal cells yet sends dense arbors of projections throughout the striatum. This review summarizes recent advances in our understanding of the factors affecting the excitability of these neurons through acute effects and long term changes in their synaptic inputs. In addition, we discuss the physiological effects of ACh in the striatum, and how changes in ACh levels may contribute to disease states during striatal dysfunction.

  19. A High Efficient Improved Soft Switched Interleaved Boost Converter

    Directory of Open Access Journals (Sweden)

    A High Efficient Improved Soft Switched Interleaved Boost Converter

    2013-06-01

    Full Text Available In this paper an improved ZVT interleaved boost PFC topology is introduced. The proposed ZVT interleaved boost converter is composed of two cell boost conversion units and an active auxiliary circuit. The proposed converter has two important advantages over the similar soft switching converters. The first one is that parallel to the main switches of the converter the auxiliary switch also operates under soft switching condition. Providing soft switching conditions for interleaved boost converters with more than one cells using only one auxiliary switch is another advantage of this topology. The prototype for the proposed converter was developed with an input of 110V ac power supply feeding a resistive output load of 600 watts. In addition, the proposed converter has the advantages of fewer structure complications, lower cost and ease of control.

  20. Heavy metal uranium affects the brain cholinergic system in rat following sub-chronic and chronic exposure

    International Nuclear Information System (INIS)

    Uranium is a heavy metal naturally present in the environment that may be chronically ingested by the population. Previous studies have shown that uranium is present in the brain and alters behaviour, notably locomotor activity, sensorimotor ability, sleep/wake cycle and the memory process, but also metabolism of neurotransmitters. The cholinergic system mediates many cognitive systems, including those disturbed after chronic exposure to uranium i.e., spatial memory, sleep/wake cycle and locomotor activity. The objective of this study was to assess whether these disorders follow uranium-induced alteration of the cholinergic system. In comparison with 40 control rats, 40 rats drank 40 mg/L uranyl nitrate for 1.5 or 9 months. Cortex and hippocampus were removed and gene expression and protein level were analysed to determine potential changes in cholinergic receptors and acetylcholine levels. The expression of genes showed various alterations in the two brain areas after short- and long-term exposure. Nevertheless, protein levels of the choline acetyltransferase enzyme (ChAT), the vesicular transporter of acetylcholine (VAChT) and the nicotinic receptor β2 sub-unit (nAChRβ2) were unmodified in all cases of the experiment and muscarinic receptor type 1 (m1AChR) protein level was disturbed only after 9 months of exposure in the cortex (-30%). Acetylcholine levels were unchanged in the hippocampus after 1.5 and 9 months, but were decreased in the cortex after 1.5 months only (-22%). Acetylcholinesterase (AChE) activity was also unchanged in the hippocampus but decreased in the cortex after 1.5 and 9 months (-16% and -18%, respectively). Taken together, these data indicate that the cholinergic system is a target of uranium exposure in a structure-dependent and time-dependent manner. These cholinergic alterations could participate in behavioural impairments.

  1. Philippine campaign boosts child immunizations.

    Science.gov (United States)

    Manuel-santana, R

    1993-03-01

    In 1989, USAID awarded the Philippines a 5-year, US $50 million Child Survival Program targeting improvement in immunization coverage of children, prenatal care coverage for pregnant women, and contraceptive prevalence. Upon successful completion of performance benchmarks at the end of each year, USAID released monies to fund child survival activities for the following year. This program accomplished a major program goal, which was decentralization of health planning. The Philippine Department of Health soon incorporated provincial health planning. The Philippine Department of Health soon incorporated provincial health planning in its determination of allocation of resources. Social marketing activities contributed greatly to success in achieving the goal of boosting the immunization coverage rate for the 6 antigens listed under the Expanded Program for Immunization (51%-85% of infants, 1986-1991). In fact, rural health officers in Tarlac Province in Central Luzon went from household to household to talk to mothers about the benefits of immunizing a 1-year-old child, thereby contributing greatly to their achieving a 95% full immunization coverage rate by December 1991. Social marketing techniques included modern marketing strategies and multimedia channels. They first proved successful in metro Manila which, at the beginning of the campaign, had the lowest immunization rate of all 14 regions. Every Wednesday was designated immunization day and was when rural health centers vaccinated the children. Social marketing also successfully publicized oral rehydration therapy (ORT), breast feeding, and tuberculosis control. Another contributing factor to program success in child survival activities was private sector involvement. For example, the Philippine Pediatric Society helped to promote ORT as the preferred treatment for acute diarrhea. Further, the commercial sector distributed packets of oral rehydration salts and even advertised its own ORT product. At the end of 2

  2. Cholinergic modulation of cognitive processing: insights drawn from computational models

    Directory of Open Access Journals (Sweden)

    Ehren L Newman

    2012-06-01

    Full Text Available Acetylcholine plays an important role in cognitive function, as shown by pharmacological manipulations that impact working memory, attention, episodic memory and spatial memory function. Acetylcholine also shows striking modulatory influences on the cellular physiology of hippocampal and cortical neurons. Modeling of neural circuits provides a framework for understanding how the cognitive functions may arise from the influence of acetylcholine on neural and network dynamics. We review the influences of cholinergic manipulations on behavioral performance in working memory, attention, episodic memory and spatial memory tasks, the physiological effects of acetylcholine on neural and circuit dynamics, and the computational models that provide insight into the functional relationships between the physiology and behavior. Specifically, we discuss the important role of acetylcholine in governing mechanisms of active maintenance in working memory tasks and in regulating network dynamics important for effective processing of stimuli in attention and episodic memory tasks. We also propose that theta rhythm play a crucial role as an intermediary between the physiological influences of acetylcholine and behavior in episodic and spatial memory tasks. We conclude with a synthesis of the existing modeling work and highlight future directions that are likely to be rewarding given the existing state of the literature for both empiricists and modelers.

  3. Localization of the M2 muscarinic cholinergic receptor in dendrites, cholinergic terminals, and noncholinergic terminals in the rat basolateral amygdala: An ultrastructural analysis.

    Science.gov (United States)

    Muller, Jay F; Mascagni, Franco; Zaric, Violeta; Mott, David D; McDonald, Alexander J

    2016-08-15

    Activation of M2 muscarinic receptors (M2Rs) in the rat anterior basolateral nucleus (BLa) is critical for the consolidation of memories of emotionally arousing events. The present investigation used immunocytochemistry at the electron microscopic level to determine which structures in the BLa express M2Rs. In addition, dual localization of M2R and the vesicular acetylcholine transporter protein (VAChT), a marker for cholinergic axons, was performed to determine whether M2R is an autoreceptor in cholinergic axons innervating the BLa. M2R immunoreactivity (M2R-ir) was absent from the perikarya of pyramidal neurons, with the exception of the Golgi complex, but was dense in the proximal dendrites and axon initial segments emanating from these neurons. Most perikarya of nonpyramidal neurons were also M2R-negative. About 95% of dendritic shafts and 60% of dendritic spines were M2 immunoreactive (M2R(+) ). Some M2R(+) dendrites had spines, suggesting that they belonged to pyramidal cells, whereas others had morphological features typical of nonpyramidal neurons. M2R-ir was also seen in axon terminals, most of which formed asymmetrical synapses. The main targets of M2R(+) terminals forming asymmetrical (putative excitatory) synapses were dendritic spines, most of which were M2R(+) . The main targets of M2R(+) terminals forming symmetrical (putative inhibitory or neuromodulatory) synapses were unlabeled perikarya and M2R(+) dendritic shafts. M2R-ir was also seen in VAChT(+) cholinergic terminals, indicating a possible autoreceptor role. These findings suggest that M2R-mediated mechanisms in the BLa are very complex, involving postsynaptic effects in dendrites as well as regulating release of glutamate, γ-aminobutyric acid, and acetylcholine from presynaptic axon terminals. J. Comp. Neurol. 524:2400-2417, 2016. © 2016 Wiley Periodicals, Inc. PMID:26779591

  4. Satureja bachtiarica ameliorate beta-amyloid induced memory impairment, oxidative stress and cholinergic deficit in animal model of Alzheimer's disease.

    Science.gov (United States)

    Soodi, Maliheh; Saeidnia, Soodabeh; Sharifzadeh, Mohammad; Hajimehdipoor, Homa; Dashti, Abolfazl; Sepand, Mohammad Reza; Moradi, Shahla

    2016-04-01

    Extracellular deposition of Beta-amyloid peptide (Aβ) is the main finding in the pathophysiology of Alzheimer's disease (AD), which damages cholinergic neurons through oxidative stress and reduces the cholinergic neurotransmission. Satureja bachtiarica is a medicinal plant from the Lamiaceae family which was widely used in Iranian traditional medicine. The aim of the present study was to investigate possible protective effects of S. bachtiarica methanolic extract on Aβ induced spatial memory impairment in Morris Water Maze (MWM), oxidative stress and cholinergic neuron degeneration. Pre- aggregated Aβ was injected into the hippocampus of each rat bilaterally (10 μg/rat) and MWM task was performed 14 days later to evaluate learning and memory function. Methanolic extract of S.bachtiarica (10, 50 and 100 mg/Kg) was injected intraperitoneally for 19 consecutive days, after Aβ injection. After the probe test the brain tissue were collected and lipid peroxidation, Acetylcholinesterase (AChE) activity and Cholin Acetyl Transferees (ChAT) immunorectivity were measured in the hippocampus. Intrahipocampal injection of Aβ impaired learning and memory in MWM in training days and probe trail. Methanolic extract of S. bachtiarica (50 and 100 mg/Kg) could attenuate Aβ-induced memory deficit. ChAT immunostaining revealed that cholinergic neurons were loss in Aβ- injected group and S. bachtiarica (100 mg/Kg) could ameliorate Aβ- induced ChAT reduction in the hippocampus. Also S. bachtiarica could ameliorate Aβ-induced lipid peroxidation and AChE activity increase in the hippocampus. In conclusion our study represent that S.bachtiarica methanolic extract can improve Aβ-induced memory impairment and cholinergic loss then we recommended this extract as a candidate for further investigation in treatment of AD. PMID:26638718

  5. Endogenous cholinergic neurotransmission contributes to behavioral sensitization to morphine.

    Directory of Open Access Journals (Sweden)

    Dusica Bajic

    Full Text Available Neuroplasticity in the mesolimbic dopaminergic system is critical for behavioral adaptations associated with opioid reward and addiction. These processes may be influenced by cholinergic transmission arising from the laterodorsal tegmental nucleus (LDTg, a main source of acetylcholine to mesolimbic dopaminergic neurons. To examine this possibility we asked if chronic systemic morphine administration affects expression of genes in ventral and ventrolateral periaqueductal gray at the level of the LDTg using rtPCR. Specifically, we examined gene expression changes in the area of interest using Neurotransmitters and Receptors PCR array between chronic morphine and saline control groups. Analysis suggested that chronic morphine administration led to changes in expression of genes associated, in part, with cholinergic neurotransmission. Furthermore, using a quantitative immunofluorescent technique, we found that chronic morphine treatment produced a significant increase in immunolabeling of the cholinergic marker (vesicular acetylcholine transporter in neurons of the LDTg. Finally, systemic administration of the nonselective and noncompetitive neuronal nicotinic antagonist mecamylamine (0.5 or 2 mg/kg dose-dependently blocked the expression, and to a lesser extent the development, of locomotor sensitization. The same treatment had no effect on acute morphine antinociception, antinociceptive tolerance or dependence to chronic morphine. Taken together, the results suggest that endogenous nicotinic cholinergic neurotransmission selectively contributes to behavioral sensitization to morphine and this process may, in part, involve cholinergic neurons within the LDTg.

  6. Characterization of a novel mechanism accounting for the adverse cholinergic effects of the anticancer drug irinotecan

    Science.gov (United States)

    Blandizzi, Corrado; De Paolis, Barbara; Colucci, Rocchina; Lazzeri, Gloria; Baschiera, Fabio; Del Tacca, Mario

    2001-01-01

    This study investigates the mechanisms accounting for the adverse cholinergic effects of the antitumour drug irinotecan. The activity of irinotecan and its active metabolite, 7-ethyl-10-hydroxy-camptothecin (SN-38), was assayed in models suitable for pharmacological studies on cholinergic system. Irinotecan moderately inhibited human or electric eel acetylcholinesterase activity, SN-38 had no effect, whereas physostigmine blocked both the enzymes with high potency and efficacy. Irinotecan and SN-38 did not affect spontaneous or electrically-induced contractile activity of human colonic muscle. Acetylcholine and dimethylphenylpiperazinium (DMPP) caused phasic contractions or relaxations, respectively. Physostigmine enhanced the motor responses elicited by electrical stimulation. Although irinotecan and SN-38 did not modify the basal contractile activity of guinea-pig ileum longitudinal muscle strips, irinotecan 100 μM moderately enhanced cholinergic twitch contractions. Acetylcholine or DMPP caused phasic contractions, whereas physostigmine enhanced the twitch responses. Electrically-induced [3H]-acetylcholine release was reduced by irinotecan (100 μM) or physostigmine (0.1 μM). Intravenous irinotecan stimulated gastric acid secretion in rats, but no effects were obtained with SN-38, physostigmine or i.c.v. irinotecan. Hypersecretion induced by irinotecan was partly prevented by ondansetron, and unaffected by capsazepine. In the presence of atropine, vagotomy and systemic or vagal ablation of capsaicin-sensitive afferent fibres, irinotecan did not stimulate gastric secretion. The present results indicate that irinotecan and SN-38 do not act as specific acetylcholinesterase blockers or acetylcholine receptor agonists. It is rather suggested that irinotecan promotes a parasympathetic discharge to peripheral organs, mediated by capsaicin-sensitive vagal afferent fibres, and that serotonin 5-HT3 receptors are implicated in the genesis of vago-vagal reflex

  7. The cholinergic ligand binding material of axonal membranes

    International Nuclear Information System (INIS)

    Choline acetyltransferase and acetylcholinesterase, the enzymes responsible for the synthesis and hydrolysis of ACh, are present in nerve fibers. In crustacean peripheral nerves, release of ACh from cut nerve fibers has been demonstrated. Previously closed membrane vesicles have been prepared from lobster walking leg nerve plasma membrane and saturable binding of cholinergic agonsist and antagonists to such membranes have been demonstrated. This paper studies this axonal cholinergic binding material, and elucidates its functions. The binding of tritium-nicotine to lobster nerve plasma membranes was antagonized by a series of cholinergic ligands as well as by a series of local anesthetics. This preparation was capable of binding I 125-alpha-bungarotoxin, a ligand widely believed to be a specific label for nicotinic ACh receptor. The labelling of 50 K petide band with tritium-MBTA following disulfide reduction is illustrated

  8. Cholinergic neurotransmission in human corpus cavernosum. II. Acetylcholine synthesis

    International Nuclear Information System (INIS)

    Physiological and histochemical evidence indicates that cholinergic nerves may participate in mediating penile erection. Acetylcholine synthesis and release was studied in isolated human corporal tissue. Human corpus cavernosum incubated with [3H]choline accumulated [3H]choline and synthesized [3H]acethylcholine in an concentration-dependent manner. [3H]Acetylcholine accumulation by the tissue was inhibited by hemicholinium-3, a specific antagonist of the high-affinity choline transport in cholinergic nerves. Transmural electrical field stimulation caused release of [3H]acetylcholine which was significantly diminished by inhibiting neurotransmission with calcium-free physiological salt solution or tetrodotoxin. These observations provide biochemical and physiological evidence for the existence of cholinergic innervation in human corpus cavernosum

  9. Boost.Asio C++ network programming

    CERN Document Server

    Torjo, John

    2013-01-01

    What you want is an easy level of abstraction, which is just what this book provides in conjunction with Boost.Asio. Switching to Boost.Asio is just a few extra #include directives away, with the help of this practical and engaging guide.This book is great for developers that need to do network programming, who don't want to delve into the complicated issues of a raw networking API. You should be familiar with core Boost concepts, such as smart pointers and shared_from_this, resource classes (noncopyable), functors and boost::bind, boost mutexes, and the boost date/time library. Readers should

  10. Boosted Horizon of a Boosted Space-Time Geometry

    CERN Document Server

    Battista, Emmanuele; Scudellaro, Paolo; Tramontano, Francesco

    2015-01-01

    We apply the ultrarelativistic boosting procedure to map the metric of Schwarzschild-de Sitter spacetime into a metric describing de Sitter spacetime plus a shock-wave singularity located on a null hypersurface, by exploiting the picture of the embedding of an hyperboloid in a five-dimensional Minkowski spacetime. After reverting to the usual four-dimensional formalism, we also solve the geodesic equation and evaluate the Riemann curvature tensor of the boosted Schwarzschild-de Sitter metric by means of numerical calculations, which make it possible to reach the ultrarelativistic regime gradually by letting the boost velocity approach the speed of light. Eventually, the analysis of the Kretschmann invariant (and of the geodesic equation) shows the global structure of space- time, as we demonstrate the presence of a "scalar curvature singularity" within a 3-sphere and find that it is also possible to define what we have called "boosted horizon", a sort of elastic wall where all particles are surprisingly pushe...

  11. A Low Cost Single-Switch Bridgeless Boost PFC Converter

    Directory of Open Access Journals (Sweden)

    Younghoon Cho

    2014-03-01

    Full Text Available This paper proposes the single-switch bridgeless boost power factor correction (PFC converter to achieve high efficiency in low cost. The proposed converter utilizes only one active switching device for PFC operation as well as expecting higher efficiency than typical boost PFC converters. On the other hand, the implementation cost is less than traditional bridgeless boost PFC converters, in where two active switching deivces are necessary. The operational principle, the modeling, and the control scheme of the proposed converter are discussed in detail. In order to verify the operation of the proposed converter, a 500W switching model is built in PSIM software package. The simulation results show that the proposed converter perfectly achieves PFC operation with only a single active switch.

  12. Local infusion of interleukin-6 attenuates the neurotoxic effects of NMDA on rat striatal cholinergic neurons.

    Science.gov (United States)

    Toulmond, S; Vige, X; Fage, D; Benavides, J

    1992-09-14

    The potential neuroprotective effects of IL-6 against the excitotoxic neuronal loss induced by N-methyl-D-aspartate (NMDA) have been studied. Infusion into the rat striatum of excitotoxic amounts (250 nmol) of NMDA resulted in a 45% decrease in striatal choline acetyl transferase activity (ChAT; a marker of cholinergic neurons) and glutamate decarboxylase (GAD, a marker of GABAergic neurons) at 2 days post-injection. Co-infusion of 10 U of IL-6 reduced the loss of ChAT activity to 21% but failed to prevent the loss of GAD activity. IL-6 per se, up to the dose of 500 U, failed to affect ChAT or GAD activities. The in vivo effects of IL-6 are not mediated by a direct antagonism of NMDA toxicity, since IL-6 (up to a concentration of 500 and 5000 U/ml, respectively) did not antagonize either the increase in cyclic GMP levels resulting from NMDA receptor activation in cerebellar slices or the glutamate-induced release of lactate dehydrogenase, an index of neurotoxicity, by cultured cortical neurons. These results suggest that the increase in IL-6 levels observed in experimental brain lesions may play a role in the protection and regeneration of cholinergic neurons. PMID:1331914

  13. Boosting Applied to Word Sense Disambiguation

    OpenAIRE

    Escudero, Gerard; Marquez, Lluis; Rigau, German

    2000-01-01

    In this paper Schapire and Singer's AdaBoost.MH boosting algorithm is applied to the Word Sense Disambiguation (WSD) problem. Initial experiments on a set of 15 selected polysemous words show that the boosting approach surpasses Naive Bayes and Exemplar-based approaches, which represent state-of-the-art accuracy on supervised WSD. In order to make boosting practical for a real learning domain of thousands of words, several ways of accelerating the algorithm by reducing the feature space are s...

  14. Cytochemical demonstration of cholinergic, serotoninergic and peptidergic nerve elements in Gorgoderina vitelliloba (Trematoda: Digenea).

    Science.gov (United States)

    McKay, D M; Halton, D W; Johnston, C F; Fairweather, I; Shaw, C

    1991-02-01

    Standard enzyme cytochemical and indirect immunocytochemical techniques have been used in conjunction with light and confocal scanning laser microscopy (CSLM) to visualize cholinergic, serotoninergic and peptidergic nerve elements in whole-mount preparations of the amphibian urinary-bladder fluke, Gorgoderina vitelliloba. Cholinesterase (ChE) activity was localized in paired anterior ganglia, a connecting dorsal commissure and in the origins of the ventral nerve cords. Cholinergic ganglia were also evident in shelled embryos in the uterus. Serotonin-immunoreactivity (IR) was more extensive than ChE activity and was identified in both the central and peripheral nervous systems. Serotoninergic nerve fibres were associated with the somatic musculature and female reproductive ducts. Antisera to nine mammalian peptides and one invertebrate (FMRFamide) peptide have been used to investigate the peptidergic nervous system in the parasite. Immunoreactivity was obtained to five peptides, namely pancreatic polypeptide (PP), peptide YY (PYY), neuropeptide Y (NPY), substance P (SP) and FMRFamide. Peptidergic nerve fibres were found to be more abundant than demonstrable cholinergic or serotoninergic nerve fibres. NPY-IR was identified only in the main components of the central nervous system. However, PP- and PYY-IR occurred in the anterior ganglia, dorsal commissure, main nerve cords and in numerous small varicose fibres that ramified throughout the worm. Additionally, PP-immunoreactive nerve fibres were found to innervate the musculature of the female reproductive tracts. Six sites of IR were found in the acetabulum, using antisera directed towards the C-terminal end of PP and PYY, and these matched with the distribution of six non-ciliated rosette-like papillae observed by scanning electron microscopy. SP- and FMRFamide-IR were identified in the CNS, and FMRFamide-immunopositive nerve fibres were also evident in association with the gonopore cirrus region and with the

  15. Developmental alterations of the septohippocampal cholinergic projection in a lissencephalic mouse model.

    Science.gov (United States)

    Garcia-Lopez, Raquel; Pombero, Ana; Dominguez, Eduardo; Geijo-Barrientos, Emilio; Martinez, Salvador

    2015-09-01

    LIS1 is one of principal genes related with Type I lissencephaly, a severe human brain malformation characterized by abnormal neuronal migration in the cortex. The LIS1 gene encodes a brain-specific 45kDa non-catalytic subunit of platelet-activating factor (PAF) acetylhydrolase-1b (PAFAH1b), an enzyme that inactivates the PAF. We have studied the role of Lis1 using a Lis1/sLis1 murine model, which has deleted the first coding exon from Lis1 gene. Homozygous mice are not viable but heterozygous have shown a delayed corticogenesis and neuronal dysplasia, with enhanced cortical excitability. Lis1/sLis1 embryos also exhibited a delay of cortical innervation by the thalamocortical fibers. We have explored in Lis1/sLis1 mice anomalies in forebrain cholinergic neuron development, which migrate from pallium to subpallium, and functionally represent the main cholinergic input to the cerebral cortex, modulating cortical activity and facilitating attention, learning, and memory. We hypothesized that primary migration anomalies and/or disorganized cortex could affect cholinergic projections from the basal forebrain and septum in Lis1/sLis1 mouse. To accomplish our objective we have first studied basal forebrain neurons in Lis1/sLis1 mice during development, and described structural and hodological differences between wild-type and Lis1/sLis1 embryos. In addition, septohippocampal projections showed altered development in mutant embryos. Basal forebrain abnormalities could contribute to hippocampal excitability anomalies secondary to Lis1 mutations and may explain the cognitive symptoms associated to cortical displasia-related mental diseases and epileptogenic syndromes. PMID:26079645

  16. Basal ganglia cholinergic and dopaminergic function in progressive supranuclear palsy.

    Science.gov (United States)

    Warren, Naomi M; Piggott, Margaret A; Greally, Elizabeth; Lake, Michelle; Lees, Andrew J; Burn, David J

    2007-08-15

    Progressive Supranuclear Palsy (PSP) is a progressive neurodegenerative disorder. In contrast to Parkinson's disease (PD) and dementia with Lewy bodies (DLB), replacement therapy with dopaminergic and cholinergic agents in PSP has been disappointing. The neurochemical basis for this is unclear. Our objective was to measure dopaminergic and cholinergic receptors in the basal ganglia of PSP and control brains. We measured, autoradiographically, dopaminergic (dopamine transporter, 125I PE2I and dopamine D2 receptors, 125I epidepride) and cholinergic (nicotinic alpha4beta2 receptors, 125I 5IA85380 and muscarinic M1 receptors, 3H pirenzepine) parameters in the striatum and pallidum of pathologically confirmed PSP cases (n=15) and controls (n=32). In PSP, there was a marked loss of dopamine transporter and nicotinic alpha4beta2 binding in the striatum and pallidum, consistent with loss of nigrostriatal neurones. Striatal D2 receptors were increased in the caudate and muscarinic M1 receptors were unchanged compared with controls. These results do not account for the poor response to dopaminergic and cholinergic replacement therapies in PSP, and suggest relative preservation of postsynaptic striatal projection neurones bearing D2/M1 receptors. PMID:17534953

  17. *118494 CHOLINERGIC RECEPTOR, MUSCARINIC, 3; CHRM3 [OMIM

    Lifescience Database Archive (English)

    Full Text Available FIELD NO 118494 FIELD TI 118494 CHOLINERGIC RECEPTOR, MUSCARINIC, 3; CHRM3 ;;ACETYLCHOLINE RECEP ... tones, and unilateral kidney dysfunction. He had a lean ... habitus since childhood. Urologic testing revealed ... scarinic acetylcholine receptor are hypophagic and lean . Nature 410: 207-212, 2001. FIELD CN Ada Hamosh - ...

  18. Cypermethrin Poisoning and Anti-cholinergic Medication- A Case Report

    Directory of Open Access Journals (Sweden)

    Dr Sudip Parajuli

    2006-07-01

    Full Text Available A 30 years old male was brought to emergency department of Manipal Teaching Hospital, Pokhara, Nepal with alleged history of consumption of pyrethroid compound ‘cypermethrin’. It was found to be newer insecticide poisoning reported in Nepal. We reported this case to show effectiveness of anti-cholinergic like hyosciane and chlorpheniramine maleate in the treatment of cypermethrin poisoning.

  19. Cholinergic and perfusion brain networks in Parkinson disease dementia

    Science.gov (United States)

    McKeith, Ian G.; Burn, David J.; Wyper, David J.; O'Brien, John T.; Taylor, John-Paul

    2016-01-01

    Objective: To investigate muscarinic M1/M4 cholinergic networks in Parkinson disease dementia (PDD) and their association with changes in Mini-Mental State Examination (MMSE) after 12 weeks of treatment with donepezil. Methods: Forty-nine participants (25 PDD and 24 elderly controls) underwent 123I-QNB and 99mTc-exametazime SPECT scanning. We implemented voxel principal components (PC) analysis, producing a series of PC images of patterns of interrelated voxels across individuals. Linear regression analyses derived specific M1/M4 and perfusion spatial covariance patterns (SCPs). Results: We found an M1/M4 SCP of relative decreased binding in basal forebrain, temporal, striatum, insula, and anterior cingulate (F1,47 = 31.9, p < 0.001) in cholinesterase inhibitor–naive patients with PDD, implicating limbic-paralimbic and salience cholinergic networks. The corresponding regional cerebral blood flow SCP showed relative decreased uptake in temporoparietal and prefrontal areas (F1,47 = 177.5, p < 0.001) and nodes of the frontoparietal and default mode networks (DMN). The M1/M4 pattern that correlated with an improvement in MMSE (r = 0.58, p = 0.005) revealed relatively preserved/increased pre/medial/orbitofrontal, parietal, and posterior cingulate areas coinciding with the DMN and frontoparietal networks. Conclusion: Dysfunctional limbic-paralimbic and salience cholinergic networks were associated with PDD. Established cholinergic maintenance of the DMN and frontoparietal networks may be prerequisite for cognitive remediation following cholinergic treatment in this condition. PMID:27306636

  20. Cholinergic-opioidergic interaction in the central amygdala induces antinociception in the guinea pig

    Directory of Open Access Journals (Sweden)

    Leite-Panissi C.R.A.

    2004-01-01

    Full Text Available Several studies have demonstrated the involvement of the central nucleus of the amygdala (CEA in the modulation of defensive behavior and in antinociceptive regulation. In a previous study, we demonstrated the existence of a cholinergic-opioidergic interaction in the CEA, modulating the defensive response of tonic immobility in guinea pigs. In the present study, we investigated a similar interaction in the CEA, but now involved in the regulation of the nociceptive response. Microinjection of carbachol (2.7 nmol and morphine (2.2 nmol into the CEA promoted antinociception up to 45 min after microinjection in guinea pigs as determined by a decrease in the vocalization index in the vocalization test. This test consists of the application of a peripheral noxious stimulus (electric shock into the subcutaneous region of the thigh that provokes the emission of a vocalization response by the animal. Furthermore, the present results demonstrated that the antinociceptive effect of carbachol (2.7 nmol; N = 10 was blocked by previous administration of atropine (0.7 nmol; N = 7 or naloxone (1.3 nmol; N = 7 into the same site. In addition, the decrease in the vocalization index induced by the microinjection of morphine (2.2 nmol; N = 9 into the CEA was prevented by pretreatment with naloxone (1.3 nmol; N = 11. All sites of injection were confirmed by histology. These results indicate the involvement of the cholinergic and opioidergic systems of the CEA in the modulation of antinociception in guinea pigs. In addition, the present study suggests that cholinergic transmission may activate the release of endorphins/enkephalins from interneurons of the CEA, resulting in antinociception.

  1. Reweighting with Boosted Decision Trees

    CERN Document Server

    Rogozhnikov, A

    2016-01-01

    Machine learning tools are commonly used in modern high energy physics (HEP) experiments. Different models, such as boosted decision trees (BDT) and artificial neural networks (ANN), are widely used in analyses and even in the software triggers. In most cases, these are classification models used to select the "signal" events from data. Monte Carlo simulated events typically take part in training of these models. While the results of the simulation are expected to be close to real data, in practical cases there is notable disagreement between simulated and observed data. In order to use available simulation in training, corrections must be introduced to generated data. One common approach is reweighting - assigning weights to the simulated events. We present a novel method of event reweighting based on boosted decision trees. The problem of checking the quality of reweighting step in analyses is also discussed.

  2. Boosting Infrastructure Investments in Africa

    OpenAIRE

    Donald Kaberuka

    2011-01-01

    The absolute and relative lack of infrastructure in Africa suggests that the continent’s competitiveness could be boosted by scaling up investments in infrastructure. Such investments would facilitate domestic and international trade, enhance Africa’s integration into the global economy and promote better human development outcomes, especially, by bringing unconnected rural communities into the mainstream economy. While there are yawning gaps in all infrastructure subsectors, inadequate e...

  3. Functions of adrenergic and cholinergic nerves in canine effectors of seminal emission.

    Science.gov (United States)

    Arver, S; Sjöstrand, N O

    1982-05-01

    Spontaneous activity responses to acetylcholine (ACh), adrenaline (A), noradrenaline (NA) and barium chloride as well as the effects of various autonomic drugs on effects of field stimulation of nerves and muscle cells of isolated pieces or strips of cauda epididymidis, vas deferens, ampulla ductus deferentis and prostate of dog were studied. The main results and conclusions are: the muscles show little spontaneous activity but rhythmicity can easily be produced by e.g. stimulating agonists. The muscles are contracted by alpha-adrenoceptor stimulants. ACh has usually no or a very weak contractile effect in high concentrations. Muscles of young dogs are more sensitive to ACh. The excitatory innervation of the muscles is adrenergic and completely blocked by adrenergic neuron blockers as well as alpha-adrenoceptor blocking drugs. Stimulation of adrenergic nerves leads to maximum response already at low frequencies (4-6 Hz). This response is very similar to that provoked by a supramaximal dose of NA. Scopolamine enhances neurogenic contractile effects while physostigmine suppresses them. Hence cholinergic nerves may act by muscarinic prejunctional inhibition of the excitatory adrenergic neurotransmission rather than act directly upon the smooth muscle cells. Since secretory cells receive cholinergic innervation prejunctional inhibition of the adrenergic myomotor nerves may be of functional significance in at least the long copulatory events of the dog. PMID:6127870

  4. Administration of MPTP to the common marmoset does not alter cortical cholinergic function

    International Nuclear Information System (INIS)

    The administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to common marmosets induced persistent motor deficits and decreased concentrations of dopamine, homovanillic acid, and 3,4-dihydroxy-phenylacetic acid (DOPAC) and [3H]dopamine uptake in the caudate-putamen. There was an 80% reduction in tyrosine hydroxylase immunoreactive cells in substantia nigra. At 10 days following the start of MPTP administration, the activity of choline acetyltransferase in the thalamus and frontal cortex was unchanged compared with control animals. Similarly, specific [3H]QNB binding was unaltered. At 4-6 weeks following the start of MPTP treatment, choline acetyltransferase activity and [3H]QNB binding in the frontal cortex and thalamus remained unaffected. There was no evidence for cell loss in the nucleus basalis of Meynert or alteration in the intensity of staining for acetylcholinesterase. MPTP treatment of the common marmoset produces a nigrostriatal lesion. In contrast, MPTP did not alter cortical cholinergic function and was not neurotoxic to the cholinergic cells in the nucleus basalis of Meynert

  5. Hypothesis for synergistic toxicity of organophosphorus poisoning-induced cholinergic crisis and anaphylactoid reactions

    Energy Technology Data Exchange (ETDEWEB)

    Cowan, F.M.; Shih, T.M.; Lenz, D.E.; Madsen, J.M.; Broomfield, C.A.

    1996-08-01

    The neurotoxicity of organophosphorus (OP) compounds Involves the Inhibition of acetylchollnesterase (AChE), causing accumulation of acetyicholine (ACh) at synapses. However, cholinergic crisis may not be the sole mechanism of OP toxicity. Adverse drug reactions caused by synergistic toxicity between drugs with distinct pharmacological mechanisms are a common problem. Likewise, the multiple pharmacological activities of a single molecule might also contribute to either toxicity or efficacy. For example, certain OP compounds (e.g. soman) exhibit anti-AChE activity and also act as secretagogues by inducing mast cell degranulation with associated autacoid release and anaphylactoid reactions. Anaphylactoid shock can produce a lethal syndrome with symptoms of respiratory failure and circulatory collapse similar to the physiological sequelae observed for OP poisoning. Moreover, the major classes of drugs used as antidotes for OP intoxication can affect anaphylaxis. Acetylcholine can act as an agonist of autacoid release, and autacoids such as histamine can augment soman-Induced bronchial spasm. In concert with the demonstrably critical role of cholinergic crisis In OP toxicity, the precepts of neuroimmunology indicate that secondary adverse reactions encompassing anaphylactold reactions may complicate OP toxicity.

  6. Chronic stimulation of cultured neuronal networks boosts low frequency oscillatory activity at theta and gamma with spikes phase-locked to gamma frequencies

    OpenAIRE

    Leondopulos, Stathis S.; Boehler, Michael D.; Wheeler, Bruce C.; Brewer, Gregory J.

    2012-01-01

    Slow wave oscillations in the brain are essential for coordinated network activity but have not been shown to self-organize in vitro. Here, the development of dissociated hippocampal neurons into an active network with oscillations on multi-electrode arrays was evaluated in the absence and presence of chronic external stimulation. Significant changes in signal power were observed in the range of 1-400 Hz with an increase in amplitude during bursts. Stimulation increased oscillatory activity p...

  7. Delirium Accompanied by Cholinergic Deficiency and Organ Failure in a 73-Year-Old Critically Ill Patient: Physostigmine as a Therapeutic Option

    Directory of Open Access Journals (Sweden)

    Benedikt Zujalovic

    2015-01-01

    Full Text Available Delirium is a common problem in ICU patients, resulting in prolonged ICU stay and increased mortality. A cholinergic deficiency in the central nervous system is supposed to be a relevant pathophysiologic process in delirium. Acetylcholine is a major transmitter of the parasympathetic nervous system influencing several organs (e.g., heart and kidneys and the inflammatory response too. This perception might explain that delirium is not an individual symptom, but rather a part of a symptom complex with various disorders of the whole organism. The cholinergic deficiency could not be quantified up to now. Using the possibility of bedside determination of the acetylcholinesterase activity (AChE activity, we assumed to objectify the cholinergic homeostasis within minutes. As reported here, the postoperative delirium was accompanied by a massive hemodynamic and renal deterioration of unclear genesis. We identified the altered AChE activity as a plausible pathophysiological mechanism. The pharmacological intervention with the indirect parasympathomimetic physostigmine led to a quick and lasting improvement of the patient’s cognitive, hemodynamic, and renal status. In summary, severe delirium is not always an attendant phenomenon of critical illness. It might be causal for multiple organ deterioration if it is based on cholinergic deficiency and has to be treated at his pathophysiological roots whenever possible.

  8. Cholinergic receptor binding in the frontal cortex of suicide victims

    International Nuclear Information System (INIS)

    Because there is a high incidence of individuals diagnosed as having an affective disorder who subsequently commit suicide, the author thought it would be of interest to determine QNB binding in the brains of a large sample of suicide victims, and to compare the findings with a well-matched control group. Brain samples were obtained at autopsy from 22 suicide victims and 22 controls. Frontal cortex samples were diseected, frozen, and stored until assayed. Samples of tissue homogenate were incubated in duplicate with 10 concentrations of tritium-QNB. Specific binding was determined with and without atropine. The results confirmed previous studies in which no changes were noted in suicide versus control brains. While the findings neither disprove nor support the cholinergic hypothesis of depression, they do suggest that the neurochemical basis for the in vivo observations of increased responsivity of depressed individuals to muscarinic cholinergic agents might not involve changes in receptors estimated by QNB binding

  9. Involvement of M3 Cholinergic Receptor Signal Transduction Pathway in Regulation of the Expression of Chemokine MOB-1, MCP-1 Genes in Pancreatic Acinar Cells

    Institute of Scientific and Technical Information of China (English)

    郑海; 陈道达; 张景輝; 田原

    2004-01-01

    Whether M3 cholinergic receptor signal transduction pathway is involved in regulation of the activation of NF-κB and the expression of chemokine MOB-1, MCP-1genes in pancreatic acinar cells was investigated. Rat pancreatic acinar cells were isolated, cultured and treated with carbachol, atropine and PDTC in vitro. The MOB-1 and MCP-1 mRNA expression was detected by using RT-PCR. The activation of NF-κB was monitored by using electrophoretic mobility shift assay.The results showed that as compared with control group, M3 cholinergic receptor agonist (103mol/L, 104-4ol/L carbachol) could induce a concentration-dependent and time-dependent increase in the expression of MOB-1, MCP-1 mRNA in pancreatic acinar cells. After treatment with 10 -3mol/L carbachol for 2 h, the expression of MOB-1, MCP-1 mRNA was strongest. The activity of NF-κB in pancreatic acinar cells was significantly increased (P<0.01) after treated with M3 cholinergic receptor agonist (10-3 mol/L carbachol) in vitro for 30 min. Either M3 cholinergic receptor antagonist (10-5 mol/L atropine) or NF-κB inhibitor (10-2 mol/L PDTC) could obviously inhibit the activation of NF-κB and the chemokine MOB-1, MCP-1 mRNA expression induced by carbachol (P <0.05). This inhibitory effect was significantly increased by atropine plus PDTC (P<0.01). The results of these studies indicated that M3 cholinergic receptor signal transduction pathway was likely involved in regulation of the expression of chemokine MOB-1 and MCP-1genes in pancreatic acinar cells in vitro through the activation of NF-κB.

  10. Antagonist of the amylin receptor blocks beta-amyloid toxicity in rat cholinergic basal forebrain neurons.

    Science.gov (United States)

    Jhamandas, Jack H; MacTavish, David

    2004-06-16

    Salvage of cholinergic neurons in the brain through a blockade of the neurotoxic effects of amyloidbeta protein (Abeta) is one of the major, but still elusive, therapeutic goals of current research in Alzheimer's disease (AD). To date, no receptor has been unequivocally identified for Abeta. Human amylin, which acts via a receptor composed of the calcitonin receptor-like receptor and a receptor-associated membrane protein, possesses amyloidogenic properties and has a profile of neurotoxicity that is strikingly similar to Abeta. In this study, using primary cultures of rat cholinergic basal forebrain neurons, we show that acetyl-[Asn30, Tyr32] sCT(8-37) (AC187), an amylin receptor antagonist, blocks Abeta-induced neurotoxicity. Treatment of cultures with AC187 before exposure to Abeta results in significantly improved neuronal survival as judged by MTT and live-dead cell assays. Quantitative measures of Abeta-evoked apoptotic cell death, using Hoechst and phosphotidylserine staining, confirm neuroprotective effects of AC187. We also demonstrate that AC187 attenuates the activation of initiator and effector caspases that mediate Abeta-induced apoptotic cell death. These data are the first to show that expression of Abeta toxicity may occur through the amylin receptor and suggest a novel therapeutic target for the treatment of AD. PMID:15201330

  11. Improved Parallel Boost Power Converter for Power Factor Correction

    OpenAIRE

    T. Ajith Bosco Raj; Ramesh, R.

    2014-01-01

    The main objective of the study is to analysis and design parallel boost power converter for power factor correction using an active filtering approach by implementing single-phase soft-switching technique with an active snubber circuit. Zero voltage transition to turn ON and zero current transition to turn OFF is implemented by the active snubber circuit for the main switches with no any further current or voltage strains. By zero-current switching without the need of added voltage stress, a...

  12. Hypertension favors the endothelial non-neuronal cholinergic system

    OpenAIRE

    Zou, Qian; 鄒倩

    2013-01-01

    This thesis investigates the involvement of the non-neuronal cholinergic system in endothelium-dependent relaxations and the impact of hypertension on the function of this system. In Study1 the contribution of nicotinic receptors (nAChRs) to endothelium-dependent relaxations evoked by acetylcholine was examined. Both muscarinic (mAChRs) and nAChR were expressed in the aortic endothelium of spontaneously hypertensive (SHR)and Wistar-Kyoto rats (WKY). However, isometric tension measurements sho...

  13. Cholinergic Abnormalities, Endosomal Alterations and Up-Regulation of Nerve Growth Factor Signaling in Niemann-Pick Type C Disease

    Directory of Open Access Journals (Sweden)

    Cabeza Carolina

    2012-03-01

    Full Text Available Abstract Background Neurotrophins and their receptors regulate several aspects of the developing and mature nervous system, including neuronal morphology and survival. Neurotrophin receptors are active in signaling endosomes, which are organelles that propagate neurotrophin signaling along neuronal processes. Defects in the Npc1 gene are associated with the accumulation of cholesterol and lipids in late endosomes and lysosomes, leading to neurodegeneration and Niemann-Pick type C (NPC disease. The aim of this work was to assess whether the endosomal and lysosomal alterations observed in NPC disease disrupt neurotrophin signaling. As models, we used i NPC1-deficient mice to evaluate the central cholinergic septo-hippocampal pathway and its response to nerve growth factor (NGF after axotomy and ii PC12 cells treated with U18666A, a pharmacological cellular model of NPC, stimulated with NGF. Results NPC1-deficient cholinergic cells respond to NGF after axotomy and exhibit increased levels of choline acetyl transferase (ChAT, whose gene is under the control of NGF signaling, compared to wild type cholinergic neurons. This finding was correlated with increased ChAT and phosphorylated Akt in basal forebrain homogenates. In addition, we found that cholinergic neurons from NPC1-deficient mice had disrupted neuronal morphology, suggesting early signs of neurodegeneration. Consistently, PC12 cells treated with U18666A presented a clear NPC cellular phenotype with a prominent endocytic dysfunction that includes an increased size of TrkA-containing endosomes and reduced recycling of the receptor. This result correlates with increased sensitivity to NGF, and, in particular, with up-regulation of the Akt and PLC-γ signaling pathways, increased neurite extension, increased phosphorylation of tau protein and cell death when PC12 cells are differentiated and treated with U18666A. Conclusions Our results suggest that the NPC cellular phenotype causes neuronal

  14. Animal model of vascular dementia and its cholinergic mechanism

    Institute of Scientific and Technical Information of China (English)

    FAN Wen-hui; LI Lu-si; LIU Zhi-rong; ZHU Hong-yan; CHEN Kang-ning

    2001-01-01

    Objective: To establish a model of vascular dementia (VD) in aging rats and study primarily the cholinergic mechanism of hypomnesia. Methods: Chronic hypoperfusion of cerebral blood flow (CBF) in the forebrain was performed in aging rats with permanent bilateral common carotid arteries occlusion (PBCCAO). Then the rats were tested with a computerized shuttle-training case. The changes of cerebrovascular system were observed with digital subtraction angiography (DSA). The brain tissues were studied with immunohistochemical method with cholinergic acetyltransferase (ChAT) as a marker. Results: The cognitive function of rats was obviously reduced in 2 months after chronic cerebral hypoperfusion and became worse 2 months later, showing a more marked decrease of ChAT positive neurons and fibers in CA1 of the hippocampus as compared with the rats of the control, which had a significant positive correlation with memory ability. Conclusion: This rat model is successfully established to imitate human VD induced with chronic cerebral hypoperfusion. The mechanism of the hypomnesia of VD might be the impairment of cholinergic neurons in frontal cortex and hippocampus.

  15. Dysfunctional penile cholinergic nerves in diabetic impotent men

    International Nuclear Information System (INIS)

    Impotence in the diabetic man may be secondary to a neuropathic condition of the autonomic penile nerves. The relationship between autonomic neuropathy and impotence in diabetes was studied in human corporeal tissue obtained during implantation of a penile prosthesis in 19 impotent diabetic and 15 nondiabetic patients. The functional status of penile cholinergic nerves was assessed by determining their ability to accumulate tritiated choline (34), and synthesize (34) and release (19) tritiated-acetylcholine after incubation of corporeal tissue with tritiated-choline (34). Tritiated-choline accumulation, and tritiated-acetylcholine synthesis and release were significantly reduced in the corporeal tissue from diabetic patients compared to that from nondiabetic patients (p less than 0.05). The impairment in acetylcholine synthesis worsened with the duration of diabetes (p less than 0.025). No differences in the parameters measured were found between insulin-dependent (11) and noninsulin-dependent (8) diabetic patients. The ability of the cholinergic nerves to synthesize acetylcholine could not be predicted clinically with sensory vibration perception threshold testing. It is concluded that there is a functional penile neuropathic condition of the cholinergic nerves in the corpus cavernosum of diabetic impotent patients that may be responsible for the erectile dysfunction

  16. Dysfunctional penile cholinergic nerves in diabetic impotent men

    Energy Technology Data Exchange (ETDEWEB)

    Blanco, R.; Saenz de Tejada, I.; Goldstein, I.; Krane, R.J.; Wotiz, H.H.; Cohen, R.A. (Boston Univ. School of Medicine, MA (USA))

    1990-08-01

    Impotence in the diabetic man may be secondary to a neuropathic condition of the autonomic penile nerves. The relationship between autonomic neuropathy and impotence in diabetes was studied in human corporeal tissue obtained during implantation of a penile prosthesis in 19 impotent diabetic and 15 nondiabetic patients. The functional status of penile cholinergic nerves was assessed by determining their ability to accumulate tritiated choline (34), and synthesize (34) and release (19) tritiated-acetylcholine after incubation of corporeal tissue with tritiated-choline (34). Tritiated-choline accumulation, and tritiated-acetylcholine synthesis and release were significantly reduced in the corporeal tissue from diabetic patients compared to that from nondiabetic patients (p less than 0.05). The impairment in acetylcholine synthesis worsened with the duration of diabetes (p less than 0.025). No differences in the parameters measured were found between insulin-dependent (11) and noninsulin-dependent (8) diabetic patients. The ability of the cholinergic nerves to synthesize acetylcholine could not be predicted clinically with sensory vibration perception threshold testing. It is concluded that there is a functional penile neuropathic condition of the cholinergic nerves in the corpus cavernosum of diabetic impotent patients that may be responsible for the erectile dysfunction.

  17. Cholinergic and behavioral neurotoxicity of carbaryl and cadmium to larval rainbow trout (Oncorhynchus mykiss).

    Science.gov (United States)

    Beauvais, S L; Jones, S B; Parris, J T; Brewer, S K; Little, E E

    2001-05-01

    Pesticides and heavy metals are common environmental contaminants that can cause neurotoxicity to aquatic organisms, impairing reproduction and survival. Neurotoxic effects of cadmium and carbaryl exposures were estimated in larval rainbow trout (RBT; Oncorhynchus mykiss) using changes in physiological endpoints and correlations with behavioral responses. Following exposures, RBT were videotaped to assess swimming speed. Brain tissue was used to measure cholinesterase (ChE) activity, muscarinic cholinergic receptor (MChR) number, and MChR affinity. ChE activity decreased with increasing concentrations of carbaryl but not of cadmium. MChR were not affected by exposure to either carbaryl or cadmium. Swimming speed correlated with ChE activity in carbaryl-exposed RBT, but no correlation occurred in cadmium-exposed fish. Thus, carbaryl exposure resulted in neurotoxicity reflected by changes in physiological and behavioral parameters measured, while cadmium exposure did not. Correlations between behavior and physiology provide a useful assessment of neurotoxicity. PMID:11386719

  18. The development of the cholinergic system in rat hippocampus following postnatal X-irradiation

    International Nuclear Information System (INIS)

    Postnatal X-irradiation of the rat hippocampus results in a marked reduction in the number of the postnatally developing granular neurons in the dentate gyrus and also caused a marked increase in the specific activity of acetylcholinesterase (AChE) and choline acetyltransferase (CAT) and a slight but consistent increase in the activity per whole hippocampus of AChE. The effect of irradiation on the granular neurons and on the cholinergic enzymes was found to be dose and age dependent. Drastic increase in specific enzymatic activities is also observed in the irradiated cerebellum whose granular neurons differentiate postnatally and to a lesser extent in the cerebral cortex in which cell formation is accomplished prior to birth. (Auth.)

  19. Striatal Cholinergic Interneurons Control Motor Behavior and Basal Ganglia Function in Experimental Parkinsonism.

    Science.gov (United States)

    Maurice, Nicolas; Liberge, Martine; Jaouen, Florence; Ztaou, Samira; Hanini, Marwa; Camon, Jeremy; Deisseroth, Karl; Amalric, Marianne; Kerkerian-Le Goff, Lydia; Beurrier, Corinne

    2015-10-27

    Despite evidence showing that anticholinergic drugs are of clinical relevance in Parkinson's disease (PD), the causal role of striatal cholinergic interneurons (CINs) in PD pathophysiology remains elusive. Here, we show that optogenetic inhibition of CINs alleviates motor deficits in PD mouse models, providing direct demonstration for their implication in parkinsonian motor dysfunctions. As neural correlates, CIN inhibition in parkinsonian mice differentially impacts the excitability of striatal D1 and D2 medium spiny neurons, normalizes pathological bursting activity in the main basal ganglia output structure, and increases the functional weight of the direct striatonigral pathway in cortical information processing. By contrast, CIN inhibition in non-lesioned mice does not affect locomotor activity, equally modulates medium spiny neuron excitability, and does not modify spontaneous or cortically driven activity in the basal ganglia output, suggesting that the role of these interneurons in motor function is highly dependent on dopamine tone. PMID:26489458

  20. Striatal Cholinergic Interneurons Control Motor Behavior and Basal Ganglia Function in Experimental Parkinsonism

    Directory of Open Access Journals (Sweden)

    Nicolas Maurice

    2015-10-01

    Full Text Available Despite evidence showing that anticholinergic drugs are of clinical relevance in Parkinson’s disease (PD, the causal role of striatal cholinergic interneurons (CINs in PD pathophysiology remains elusive. Here, we show that optogenetic inhibition of CINs alleviates motor deficits in PD mouse models, providing direct demonstration for their implication in parkinsonian motor dysfunctions. As neural correlates, CIN inhibition in parkinsonian mice differentially impacts the excitability of striatal D1 and D2 medium spiny neurons, normalizes pathological bursting activity in the main basal ganglia output structure, and increases the functional weight of the direct striatonigral pathway in cortical information processing. By contrast, CIN inhibition in non-lesioned mice does not affect locomotor activity, equally modulates medium spiny neuron excitability, and does not modify spontaneous or cortically driven activity in the basal ganglia output, suggesting that the role of these interneurons in motor function is highly dependent on dopamine tone.

  1. Intrinsic membrane plasticity via increased persistent sodium conductance of cholinergic neurons in the rat laterodorsal tegmental nucleus contributes to cocaine-induced addictive behavior.

    Science.gov (United States)

    Kamii, Hironori; Kurosawa, Ryo; Taoka, Naofumi; Shinohara, Fumiya; Minami, Masabumi; Kaneda, Katsuyuki

    2015-05-01

    The laterodorsal tegmental nucleus (LDT) is a brainstem nucleus implicated in reward processing and is one of the main sources of cholinergic afferents to the ventral tegmental area (VTA). Neuroplasticity in this structure may affect the excitability of VTA dopamine neurons and mesocorticolimbic circuitry. Here, we provide evidence that cocaine-induced intrinsic membrane plasticity in LDT cholinergic neurons is involved in addictive behaviors. After repeated experimenter-delivered cocaine exposure, ex vivo whole-cell recordings obtained from LDT cholinergic neurons revealed an induction of intrinsic membrane plasticity in regular- but not burst-type neurons, resulting in increased firing activity. Pharmacological examinations showed that increased riluzole-sensitive persistent sodium currents, but not changes in Ca(2+) -activated BK, SK or voltage-dependent A-type potassium conductance, mediated this plasticity. In addition, bilateral microinjection of riluzole into the LDT immediately before the test session in a cocaine-induced conditioned place preference (CPP) paradigm inhibited the expression of cocaine-induced CPP. These findings suggest that intrinsic membrane plasticity in LDT cholinergic neurons is causally involved in the development of cocaine-induced addictive behaviors. PMID:25712572

  2. Aging-related deficits in orexin/hypocretin modulation of the septo-hippocampal cholinergic system

    OpenAIRE

    Stanley, Emily M.; Fadel, Jim

    2012-01-01

    The medial septum (MS) of the basal forebrain contains cholinergic neurons that project to the hippocampus, support cognitive function, and are implicated in age-related cognitive decline. Hypothalamic orexin/hypocretin neurons innervate and modulate basal forebrain cholinergic neurons and provide direct inputs to the hippocampus. However, the precise role of orexin in modulating hippocampal cholinergic transmission—and how these interactions are altered in aging—is unknown. Here, orexin A wa...

  3. Duality and Data Dependence in Boosting /

    OpenAIRE

    Telgarsky, Matus

    2013-01-01

    Boosting algorithms produce accurate predictors for complex phenomena by welding together collections of simple predictors. In the classical method AdaBoost, as well as its immediate variants, the welding points are determined by convex optimization; unlike typical applications of convex optimization in machine learning, however, the AdaBoost scheme eschews the usual regularization and constraints used to control numerical and statistical properties. On the other hand, the data and simple pre...

  4. Positive Semidefinite Metric Learning with Boosting

    OpenAIRE

    Shen, Chunhua; Kim, Junae; Wang, Lei; Hengel, Anton van den

    2009-01-01

    The learning of appropriate distance metrics is a critical problem in image classification and retrieval. In this work, we propose a boosting-based technique, termed \\BoostMetric, for learning a Mahalanobis distance metric. One of the primary difficulties in learning such a metric is to ensure that the Mahalanobis matrix remains positive semidefinite. Semidefinite programming is sometimes used to enforce this constraint, but does not scale well. \\BoostMetric is instead based on a key observat...

  5. Adaptive Sampling for Large Scale Boosting

    OpenAIRE

    Dubout, Charles; Fleuret, Francois

    2014-01-01

    Classical Boosting algorithms, such as AdaBoost, build a strong classifier without concern for the computational cost. Some applications, in particular in computer vision, may involve millions of training examples and very large feature spaces. In such contexts, the training time of off-the-shelf Boosting algorithms may become prohibitive. Several methods exist to accelerate training, typically either by sampling the features or the examples used to train the weak learners. Even if some of th...

  6. Where boosted significances come from

    Science.gov (United States)

    Plehn, Tilman; Schichtel, Peter; Wiegand, Daniel

    2014-03-01

    In an era of increasingly advanced experimental analysis techniques it is crucial to understand which phase space regions contribute a signal extraction from backgrounds. Based on the Neyman-Pearson lemma we compute the maximum significance for a signal extraction as an integral over phase space regions. We then study to what degree boosted Higgs strategies benefit ZH and tt¯H searches and which transverse momenta of the Higgs are most promising. We find that Higgs and top taggers are the appropriate tools, but would profit from a targeted optimization towards smaller transverse momenta. MadMax is available as an add-on to MadGraph 5.

  7. Recursive bias estimation and L2 boosting

    Energy Technology Data Exchange (ETDEWEB)

    Hengartner, Nicolas W [Los Alamos National Laboratory; Cornillon, Pierre - Andre [INRA, FRANCE; Matzner - Lober, Eric [RENNE, FRANCE

    2009-01-01

    This paper presents a general iterative bias correction procedure for regression smoothers. This bias reduction schema is shown to correspond operationally to the L{sub 2} Boosting algorithm and provides a new statistical interpretation for L{sub 2} Boosting. We analyze the behavior of the Boosting algorithm applied to common smoothers S which we show depend on the spectrum of I - S. We present examples of common smoother for which Boosting generates a divergent sequence. The statistical interpretation suggest combining algorithm with an appropriate stopping rule for the iterative procedure. Finally we illustrate the practical finite sample performances of the iterative smoother via a simulation study.

  8. The role of the Cholinergic System on Plasticity in the Basolateral Nucleus of the Amygdala

    OpenAIRE

    Cline, Brandon H.

    2010-01-01

    The amygdala and the cholinergic system play important roles in learning and memory. The amygdala receives substantial cholinergic innervation and in itself ex-presses differences in this innervation. p75NTR is one of the primary receptors of cho-linergic neurons and transgenic mice that are missing exon IV of the p75 neurotro-phin receptor locus, display a change in cholinergic innervation. The loss of p75NTR can induce changes in learning and memory so it was hypothesized p75EXIV animals wo...

  9. Characterization of the cellulolytic secretome of Trichoderma harzianum during growth on sugarcane bagasse and analysis of the activity boosting effects of swollenin.

    Science.gov (United States)

    A L Rocha, Vanessa; N Maeda, Roberto; Pereira, Nei; F Kern, Marcelo; Elias, Luisa; Simister, Rachael; Steele-King, Clare; Gómez, Leonardo D; McQueen-Mason, Simon J

    2016-03-01

    This study demonstrates the production of an active enzyme cocktail produced by growing Trichoderma harzianum on sugarcane bagasse. The component enzymes were identified by LCMS-MS. Glycosyl hydrolases were the most abundant class of proteins, representing 67% of total secreted protein. Other carbohydrate active enzymes involved in cell wall deconstruction included lytic polysaccharide mono-oxygenases (AA9), carbohydrate-binding modules, carbohydrate esterases and swollenin, all present at levels of 1%. In total, proteases and lipases represented 5 and 1% of the total secretome, respectively, with the rest of the secretome being made up of proteins of unknown or putative function. This enzyme cocktail was efficient in catalysing the hydrolysis of sugarcane bagasse cellulolignin to fermentable sugars for potential use in ethanol production. Apart from mapping the secretome of T. harzianum, which is a very important tool to understand the catalytic performance of enzyme cocktails, the gene coding for T. harzianum swollenin was expressed in Aspergillus niger. This novel aspect in this work, allowed increasing the swollenin concentration by 95 fold. This is the first report about the heterologous expression of swollenin from T. harzianum, and the findings are of interest in enriching enzyme cocktail with this important accessory protein which takes part in the cellulose amorphogenesis. Despite lacking detectable glycoside activity, the addition of swollenin of T. harzianum increased by two-fold the hydrolysis efficiency of a commercial cellulase cocktail. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:327-336, 2016. PMID:26697775

  10. Electron and high-dose-rate brachytherapy boost in the conservative treatment of stage I-II breast cancer. First results of the randomized Budapest boost trial

    Energy Technology Data Exchange (ETDEWEB)

    Polgar, C.; Fodor, J. [National Institute of Oncology, Department of Radiotherapy, Budapest (Hungary); Orosz, Z. [National Institute of Oncology, Center of Experimental and Human Tumor Pathology Budapest (HU)] [and others

    2002-11-01

    Background and Aims: To evaluate the effect of electron and high-dose-rate brachytherapy (HDR BT) boost on local tumor control (LTC), side effects and cosmesis after breast-conserving surgery (BCS) in a prospective randomized study. Patients and Methods: 207 women with stage I-II breast cancer who underwent BCS were treated by 50 Gy irradiation to the whole breast and then randomly assigned to receive either a boost to the tumor bed (n=104) or no further radiotherapy (n=103). Boost treatments consisted of either 16 Gy electron irradiation (n=52) or 12-14.25 Gy HDR BT (n=52). Breast cancer-related events, side effects, and cosmetic results were assessed. Results: At a median follow-up of 5.3 years, the crude rate of local recurrence was 6.7% (7/104) with and 15.5% (16/103) without boost. The 5-year probability of LTC, relapse-free survival (RFS), and cancer-specific survival (CSS) was 92.7% vs 84.9% (p=0.049), 76.6% vs 66.2% (p=0.044), and 90.4% vs. 82.1% (p=0.053), respectively. There was no significant difference in LTC between patients treated with electron or HDR BT boost (94.2% vs 91.4%; p=0.74). On multivariate analysis, patient age <40 years (RR: 4.53), positive margin status (RR: 4.17), and high mitotic activity index (RR: 3.60) were found to be significant risk factors for local recurrence. The incidence of grade 2-3 side effects was higher in the boost arm (17.3% vs 7.8%; p=0.03). However, the rate of excellent/good cosmetic results was similar for the two arms (85.6% vs 91.3%; p=0.14). Cosmesis was rated as excellent/good in 88.5% of patients treated with HDR BT and 82.7% of patients with electron boost (p=0.29). Conclusions: Boost dose significantly improves LTC and RFS in patients treated with BCS and radiotherapy. In spite of the higher incidence of late side effects in the boost arm, boost dose is strongly recommended for patients at high risk for local recurrence. Positive or close margin status, high mitotic activity index, and young patient age

  11. Electron and high-dose-rate brachytherapy boost in the conservative treatment of stage I-II breast cancer. First results of the randomized Budapest boost trial

    International Nuclear Information System (INIS)

    Background and Aims: To evaluate the effect of electron and high-dose-rate brachytherapy (HDR BT) boost on local tumor control (LTC), side effects and cosmesis after breast-conserving surgery (BCS) in a prospective randomized study. Patients and Methods: 207 women with stage I-II breast cancer who underwent BCS were treated by 50 Gy irradiation to the whole breast and then randomly assigned to receive either a boost to the tumor bed (n=104) or no further radiotherapy (n=103). Boost treatments consisted of either 16 Gy electron irradiation (n=52) or 12-14.25 Gy HDR BT (n=52). Breast cancer-related events, side effects, and cosmetic results were assessed. Results: At a median follow-up of 5.3 years, the crude rate of local recurrence was 6.7% (7/104) with and 15.5% (16/103) without boost. The 5-year probability of LTC, relapse-free survival (RFS), and cancer-specific survival (CSS) was 92.7% vs 84.9% (p=0.049), 76.6% vs 66.2% (p=0.044), and 90.4% vs. 82.1% (p=0.053), respectively. There was no significant difference in LTC between patients treated with electron or HDR BT boost (94.2% vs 91.4%; p=0.74). On multivariate analysis, patient age <40 years (RR: 4.53), positive margin status (RR: 4.17), and high mitotic activity index (RR: 3.60) were found to be significant risk factors for local recurrence. The incidence of grade 2-3 side effects was higher in the boost arm (17.3% vs 7.8%; p=0.03). However, the rate of excellent/good cosmetic results was similar for the two arms (85.6% vs 91.3%; p=0.14). Cosmesis was rated as excellent/good in 88.5% of patients treated with HDR BT and 82.7% of patients with electron boost (p=0.29). Conclusions: Boost dose significantly improves LTC and RFS in patients treated with BCS and radiotherapy. In spite of the higher incidence of late side effects in the boost arm, boost dose is strongly recommended for patients at high risk for local recurrence. Positive or close margin status, high mitotic activity index, and young patient age

  12. Nicotine increases impulsivity and decreases willingness to exert cognitive effort despite improving attention in "slacker" rats: insights into cholinergic regulation of cost/benefit decision making.

    Directory of Open Access Journals (Sweden)

    Jay G Hosking

    Full Text Available Successful decision making in our daily lives requires weighing an option's costs against its associated benefits. The neuromodulator acetylcholine underlies both the etiology and treatment of a number of illnesses in which decision making is perturbed, including Alzheimer's disease, attention-deficit/hyperactivity disorder, and schizophrenia. Nicotine acts on the cholinergic system and has been touted as a cognitive enhancer by both smokers and some researchers for its attention-boosting effects; however, it is unclear whether treatments that have a beneficial effect on attention would also have a beneficial effect on decision making. Here we utilize the rodent Cognitive Effort Task (rCET, wherein animals can choose to allocate greater visuospatial attention for a greater reward, to examine cholinergic contributions to both attentional performance and choice based on attentional demand. Following the establishment of baseline behavior, four drug challenges were administered: nicotine, mecamylamine, scopolamine, and oxotremorine (saline plus three doses for each. As per previous rCET studies, animals were divided by their baseline preferences, with "worker" rats choosing high-effort/high-reward options more than their "slacker" counterparts. Nicotine caused slackers to choose even fewer high-effort trials than at baseline, but had no effect on workers' choice. Despite slackers' decreased willingness to expend effort, nicotine improved their attentional performance on the task. Nicotine also increased measures of motor impulsivity in all animals. In contrast, scopolamine decreased animals' choice of high-effort trials, especially for workers, while oxotremorine decreased motor impulsivity for all animals. In sum, the cholinergic system appears to contribute to decision making, and in part these contributions can be understood as a function of individual differences. While nicotine has been considered as a cognitive enhancer, these data suggest

  13. MC$^2$: Boosted AGN and star-formation activity in CIZA J2242.8+5301, a massive post-merger cluster at z=0.19

    CERN Document Server

    Sobral, David; Dawson, William A; Wittman, David; Jee, James; Röttgering, Huub; van Weeren, Reinout J; Brüggen, Marcus

    2015-01-01

    Cluster mergers may play a fundamental role in the formation and evolution of cluster galaxies. Stroe et al. (2014) revealed unexpected over-densities of candidate H$\\alpha$ emitters near the ~1 Mpc-wide shock fronts of the massive (~2x10$^{15}$M$_{\\odot}$) "Sausage" merging cluster, CIZA J2242.8+5301. We used Keck/DEIMOS and WHT/AF2 to confirm 83 H$\\alpha$ emitters in and around the merging cluster. We find that cluster star-forming galaxies in the hottest X-ray gas and/or in the cluster sub-cores (away from the shock fronts) show high [SII]6716/[SII]6761 and high [SII]6716/H$\\alpha$, implying very low electron densities (2.5 Mpc). This suggests that the shock front may have triggered remaining metal-rich gas which galaxies were able to retain into forming stars. Our observations show that the merger of impressively massive (~10$^{15}$M$_\\odot$) clusters can provide the conditions for significant star-formation and AGN activity, but, as we witness strong feedback by star-forming galaxies and AGN (and given h...

  14. RBOOST: RIEMANNIAN DISTANCE BASED REGULARIZED BOOSTING.

    Science.gov (United States)

    Liu, Meizhu; Vemuri, Baba C

    2011-03-30

    Boosting is a versatile machine learning technique that has numerous applications including but not limited to image processing, computer vision, data mining etc. It is based on the premise that the classification performance of a set of weak learners can be boosted by some weighted combination of them. There have been a number of boosting methods proposed in the literature, such as the AdaBoost, LPBoost, SoftBoost and their variations. However, the learning update strategies used in these methods usually lead to overfitting and instabilities in the classification accuracy. Improved boosting methods via regularization can overcome such difficulties. In this paper, we propose a Riemannian distance regularized LPBoost, dubbed RBoost. RBoost uses Riemannian distance between two square-root densities (in closed form) - used to represent the distribution over the training data and the classification error respectively - to regularize the error distribution in an iterative update formula. Since this distance is in closed form, RBoost requires much less computational cost compared to other regularized Boosting algorithms. We present several experimental results depicting the performance of our algorithm in comparison to recently published methods, LP-Boost and CAVIAR, on a variety of datasets including the publicly available OASIS database, a home grown Epilepsy database and the well known UCI repository. Results depict that the RBoost algorithm performs better than the competing methods in terms of accuracy and efficiency. PMID:21927643

  15. Boosting as a Product of Experts

    CERN Document Server

    Edakunni, Narayanan U; Kovacs, Tim

    2012-01-01

    In this paper, we derive a novel probabilistic model of boosting as a Product of Experts. We re-derive the boosting algorithm as a greedy incremental model selection procedure which ensures that addition of new experts to the ensemble does not decrease the likelihood of the data. These learning rules lead to a generic boosting algorithm - POE- Boost which turns out to be similar to the AdaBoost algorithm under certain assumptions on the expert probabilities. The paper then extends the POEBoost algorithm to POEBoost.CS which handles hypothesis that produce probabilistic predictions. This new algorithm is shown to have better generalization performance compared to other state of the art algorithms.

  16. In vivo mapping of cholinergic neurons in the human brain using SPECT and IBVM

    International Nuclear Information System (INIS)

    In the search for an in vivo marker of cholinergic neuronal integrity, the authors extended to human use the tracer (-)-5-[123I]iodobenzovesamicol (IBVM)). IBVM, an analog of vesamicol that binds to the acetylcholine transporter on presynaptic vesicles, was prepared with specific activity greater than 1.11 x 109 MBq mmole-1. After intravenous injection of [123I]IBVM, body distribution studies (n = 5) and brain SPECT studies (n = 5) were performed on normal human subjects (n = 10). SPECT images of the brain were collected sequentially over the first 4.5 hr following injection, and again 18 hr later. Data were realigned and transformed to stereotaxic coordinates, and localized activities were extracted for tracer kinetic analysis. The cerebral tracer input function was determined from metabolite-corrected radial arterial blood samples. The best data fit was obtained using a three-compartment model, including terms reflecting cerebral blood volume, exchange of free tracer between plasma and brain and specific binding. Dissociation of bound tracer was negligible for up to 4 hr. For the fitted parameters reflecting transport (K1) and binding site density index (k3, co-efficients of variation were approximately 8% in cortical regions of interest. Relative distributions corresponded well with post-mortem immunohistochemical values reported for the acetylcholine-synthesizing enzyme choline acetyltransferase, k3 (IBVM binding site density index), and tracer activity distribution at 22 hr, but not at 4 hr after injection. SPECT imaging of [123I]IBVM succeeds as an in vivo measure of cholinergic neuronal integrity and should be useful for the study of cerebral degenerative processes such as Alzheimer's disease. 24 refs., 4 figs., 3 tabs

  17. Implementation of Fuzzy Logic controller in Photovoltaic Power generation using Boost Converter and Boost Inverter

    Directory of Open Access Journals (Sweden)

    Abubakkar Siddik A

    2012-06-01

    Full Text Available Increasing in power demand and shortage of conventional energy sources, researchers are focused on renewable energy. The proposed solar power generation circuit consists of solar array, boost converter and boost inverter. Low voltage, of photovoltaic array, is boosted using dc-dc boost converter to charge the battery and boost inverter convert this battery voltage to high quality sinusoidal ac voltage. The output of solar power fed from boost inverter feed to autonomous load without any intermediate conversion stage and a filter. For boost converter operation duty cycle is varied through fuzzy logic controller and PWM block to regulate the converter output voltage. The ac voltage total harmonic distortion (THD obtained using this configuration is quite acceptable. The proposed power generation system has several desirable features such as low cost and compact size as number of switches used, are limited to four as against six switches used in classical two-stage inverters.

  18. Advanced Airfoils Boost Helicopter Performance

    Science.gov (United States)

    2007-01-01

    Carson Helicopters Inc. licensed the Langley RC4 series of airfoils in 1993 to develop a replacement main rotor blade for their Sikorsky S-61 helicopters. The company's fleet of S-61 helicopters has been rebuilt to include Langley's patented airfoil design, and the helicopters are now able to carry heavier loads and fly faster and farther, and the main rotor blades have twice the previous service life. In aerial firefighting, the performance-boosting airfoils have helped the U.S. Department of Agriculture's Forest Service control the spread of wildfires. In 2003, Carson Helicopters signed a contract with Ducommun AeroStructures Inc., to manufacture the composite blades for Carson Helicopters to sell

  19. ATLAS boosted object tagging 2

    CERN Document Server

    Caudron, Julien; The ATLAS collaboration

    2015-01-01

    A detailed study into the optimal techniques for identifying boosted hadronically decaying W or Z bosons is presented. Various algorithms for reconstructing, grooming and tagging bosonic jets are compared for W bosons with a wide range of transverse momenta using 8 TeV data and 8 TeV and 13 TeV MC simulations. In addition, given that a hadronic jet has been identified as resulting from the hadronic decay of a W or Z, a technique is developed to discriminate between W and Z bosons. The modeling of the tagging variables used in this technique is studied using 8 TeV pp collision data and systematic uncertainties for the tagger efficiency and fake rates are evaluated.

  20. Cholinergic interneurons are differentially distributed in the human striatum.

    Directory of Open Access Journals (Sweden)

    Javier Bernácer

    Full Text Available BACKGROUND: The striatum (caudate nucleus, CN, and putamen, Put is a group of subcortical nuclei involved in planning and executing voluntary movements as well as in cognitive processes. Its neuronal composition includes projection neurons, which connect the striatum with other structures, and interneurons, whose main roles are maintaining the striatal organization and the regulation of the projection neurons. The unique electrophysiological and functional properties of the cholinergic interneurons give them a crucial modulating function on the overall striatal response. METHODOLOGY/PRINCIPLE FINDINGS: This study was carried out using stereological methods to examine the volume and density (cells/mm(3 of these interneurons, as visualized by choline acetyltransferase (ChAT immunoreactivity, in the following territories of the CN and Put of nine normal human brains: 1 precommissural head; 2 postcommissural head; 3 body; 4 gyrus and 5 tail of the CN; 6 precommissural and 7 postcommissural Put. The distribution of ChAT interneurons was analyzed with respect to the topographical, functional and chemical territories of the dorsal striatum. The CN was more densely populated by cholinergic neurons than the Put, and their density increased along the anteroposterior axis of the striatum with the CN body having the highest neuronal density. The associative territory of the dorsal striatum was by far the most densely populated. The striosomes of the CN precommissural head and the postcommissural Put contained the greatest number of ChAT-ir interneurons. The intrastriosomal ChAT-ir neurons were abundant on the periphery of the striosomes throughout the striatum. CONCLUSIONS/SIGNIFICANCE: All these data reveal that cholinergic interneurons are differentially distributed in the distinct topographical and functional territories of the human dorsal striatum, as well as in its chemical compartments. This heterogeneity may indicate that the posterior aspects of

  1. Ultrastructural localization of cholinergic muscarinic receptors in rat brain cortical capillaries

    NARCIS (Netherlands)

    Luiten, PGM; deJong, GI; VanderZee, EA; vanDijken, H; Dijken, H. van

    1996-01-01

    Cholinergic innervation of the cerebrovasculature is known to regulate vascular tone, perfusion rate and permeability of the microvascular wall. Notably the cholinergic innervation of cerebral capillaries is of interest since these capillaries form the blood-brain barrier. Although there is a genera

  2. Mechanisms mediating cholinergic antral circular smooth muscle contraction in rats

    Institute of Scientific and Technical Information of China (English)

    Helena F Wrzos; Tarun Tandon; Ann Ouyang

    2004-01-01

    AIM: To investigate the pathway (s) mediating rat antral circular smooth muscle contractile responses to the cholinomimetic agent, bethanechol and the subtypes of muscarinic receptors mediating the cholinergic contraction.METHODS: Circular smooth muscle strips from the antrum of Sprague-Dawley rats were mounted in muscle baths in Krebs buffer. Isometric tension was recorded. Cumulative concentration-response curves were obtained for (+)-cisdioxolane (cD), a nonspecific muscarinic agonist, at 10-8-10-4 mol/L, in the presence of tetrodotoxin (TTX, 10-7 mol/L).Results were normalized to cross sectional area. A repeat concentration-response curve was obtained after incubation of the muscle for 90 min with antagonists for M1 (pirenzepine),M2 (methoctramine) and M3 (darifenacin) muscarinic receptor subtypes. The sensitivity to PTX was tested by the ip injection of 100 mg/kg of PTX 5 d before the experiment. The antral circular smooth muscles were removed from PTX-treated and non-treated rats as strips and dispersed smooth muscle cells to identify whether PTX-linked pathway mediated the contractility to bethanechol.RESULTS: A dose-dependent contractile response observed with bethanechol, was not affected by TTX. The pretreatment of rats with pertussis toxin decreased the contraction induced by bethanechol. Lack of calcium as Well as the presence of the L-type calcium channel blocker, nifedipine, also inhibited the cholinergic contraction, with a reduction in response from 2.5±0.4 g/mm2 to 1.2±0.4 g/mm2 (P<0.05). The doseresponse curves were shifted to the right by muscarinic antagonists in the following order of affinity: darifenacin(M3)>methocramine (M2)>pirenzepine (M1).CONCLUSION: The muscarinic receptors-dependent contraction of rat antral circular smooth muscles was linked to the signal transduction pathway(s) involving pertussis-toxin sensitive GTP-binding proteins and to extracellular calcium via L-type voltage gated calcium channels. The presence of the

  3. Vitamin D₃ improves decline in cognitive function and cholinergic transmission in prefrontal cortex of streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Alrefaie, Zienab; Alhayani, Abdulmone'em

    2015-01-01

    Complications of diabetes mellitus include cognitive impairments and functional changes in the brain. The present study aimed to investigate the possible beneficial effect of vitamin D3 on episodic memory and cholinergic transmission in the prefrontal cortex of streptozotocin-induced diabetic rats. Thirty male Wistar rats (150-200 g) were included into control, diabetic and diabetic supplemented with vitamin D3 groups. Diabetes was induced by single intraperitoneal injection of streptozotocin 45 mg/kg in citrate buffer. Vitamin D3 was administered orally in a dose of 500 IU/kg/day in corn oil for 10 weeks. Then rats were subjected to novel object recognition test to examine for episodic memory. Animals were sacrificed under diethyl ether anesthesia and prefrontal cortices were dissected to measure the activity of choline acetyl transferase (CAT) and acetyle choline esterase (ACE) enzymes to assess for cholinergic transmission. Diabetic rats spent significantly less time exploring the novel object compared to control animals. Vitamin D3 significantly attenuated the diabetes-induced impairment so that animals again spent significantly more time exploring the novel object. The CAT activity was significantly decreased in diabetic animals while the ACE activity was significantly increased compared to control non-diabetic animals. Diabetes-induced alterations in enzyme activity in the prefrontal cortex were mitigated by vitamin D3 supplementation. The present findings demonstrate the potential effect of vitamin D3 supplementation on cognitive function in diabetic animals. It is possible that this effect is mediated through enhancing the prefrontal cortex cholinergic transmission. PMID:25835318

  4. Orthodontics Align Crooked Teeth and Boost Self-Esteem

    Science.gov (United States)

    ... desktop! more... Orthodontics Align Crooked Teeth and Boost Self- esteem Article Chapters Orthodontics Align Crooked Teeth and Boost Self- esteem Orthodontics print full article print this chapter email ...

  5. Speak, Move, Play and Learn with Children on the Autism Spectrum: Activities to Boost Communication Skills, Sensory Integration and Coordination Using Simple Ideas from Speech and Language Pathology and Occupational Therapy

    Science.gov (United States)

    Brady, Lois Jean; Gonzalez, America X.; Zawadzki, Maciej; Presley, Corinda

    2012-01-01

    This practical resource is brimming with ideas and guidance for using simple ideas from speech and language pathology and occupational therapy to boost communication, sensory integration, and coordination skills in children on the autism spectrum. Suitable for use in the classroom, at home, and in community settings, it is packed with…

  6. Cholinergic receptors as target for cancer therapy in a systems medicine perspective.

    Science.gov (United States)

    Russo, P; Del Bufalo, A; Milic, M; Salinaro, G; Fini, M; Cesario, A

    2014-01-01

    Epithelial cells not innervated by cholinergic neurons express nicotinic and muscarinic acetylcholine (ACh) receptors (nAChR, mAChR). nAChR and mAChR are components of the auto-/paracrine-regulatory loop of non-neuronal ACh release. The cholinergic control of non-neuronal cells may be mediated by different effects (synergistic, additive, or reciprocal) triggered by these receptors. The ionic events (Ca(+2) influx) are generated by the ACh-opening of nAChR channels, while the metabolic events by ACh-binding to G-proteincoupled mAChR. Effective inter- and intracellular signaling is crucial for valuable cancer cells proliferation and survival. Depending on cancer cell type, different AChR have been identified. The proliferation of airways epithelial cancer cells and pancreatic cancer cells may be under the control of α7-nAChR and M3-mAChR, while breast cancer cells and colon cancer cells are regulated by α9-nAChR, and M3-mAChR, respectively. In turn, these receptors may activate different pathways (Ras-Raf-1-Erk-AKT) as well as other receptors (β- adrenergicR). nAChR or mAChR antagonists may inhibit cancer growth. Inhibition of M3 by antisense or antagonists (Darifenacin, Tiotropium) reduces lung or colon cancer proliferation, as well as inhibition of α9- nAChR [polyphenol (-)-epigallocatechin-3-gallate] diminishes breast cancer cells growth. α7-nAChR silencing inhibits lung cancer proliferation. Moreover, inhibition of the nAChR-β-adrenergicR pathway (β-blockers) could be also useful. This review will describe the future translational perspectives of cholinergic receptors druginhibition in a complex disease such as cancer that poses compelling treatment challenges. Cancer happens as consequence of disease-perturbed molecular networks in relevant organ cells that change during progression. The framework for approaching these challenges is a systems approach. PMID:25324001

  7. Three Phase High Power Quality Two- Stage Boost Rectifier

    Directory of Open Access Journals (Sweden)

    P.NAMMALVAR

    2012-04-01

    Full Text Available Three-phase two-stage boost rectifier with sinusoidal input current are presented and a novel topology with two active power devices is proposed. These contain a capacitor for pumping action in DC circuit. This gives twostage boost operation to obtain higher DC output voltage. The rectifier can be operated in the switch mode forpumping action and for forcing the input current to follow its sinusoidal reference independent of the working conditions. The results of the proposed rectifier are compared with those of the rectifier with a single active power device. The simulation result gives the better output DC voltage regulation under open loop condition. The simulated results prove that the proposed rectifier has the expected performance.

  8. Novel Intrusion Detection using Probabilistic Neural Network and Adaptive Boosting

    OpenAIRE

    Tich Phuoc Tran; Longbing Cao; Dat Tran; Cuong Duc Nguyen

    2009-01-01

    This article applies Machine Learning techniques to solve Intrusion Detection problems withincomputer networks. Due to complex and dynamic nature of computer networks and hacking techniques, detecting malicious activities remains a challenging task for security experts, that is, currently available defense systems suffer from low detection capability and high number of false alarms. To overcome such performance limitations, we propose a novel Machine Learning algorithm, namely Boosted Subspac...

  9. Bovine pancreatic polypeptide as an antagonist of muscarinic cholinergic receptors

    International Nuclear Information System (INIS)

    In dispersed acini from rat pancreas, it was found that bovine pancreatic polypeptide (BPP) and its C-fragment hexapeptide amide (PP-6), at concentrations of 0.1 and 30 μM, respectively, could significantly inhibit amylase secretion stimulated by carbachol, and this inhibition by BPP was dose dependent. 45Ca outflux induced by carbachol was also inhibited by BPP or PP-6, but they had no effect on cholecystokinin octapeptide- (CCK-8) or A23187-stimulated 45Ca outflux. BPP was also capable of displacing the specific binding of [3H]-quinuclidinyl benzilate to its receptors, and it possessed a higher affinity (K/sub i/35nM) than carbachol (K/sub i/ 1.8 μM) in binding with M-receptors. It is concluded from this study that BPP acts as an antagonist of muscarinic cholinergic receptors in rat pancreatic acini. In addition, BPP inhibited the potentiation of amylase secretion caused by the combination of carbachol plus secretin or vasoactive intestinal peptide. This may be a possible explanation of the inhibitory effect of BPP on secretin-induced pancreatic enzyme secretion shown in vivo, since pancreatic enzyme secretion stimulated by secretin under experimental conditions may be the result of potentiation of enzyme release produced by the peptide in combination with a cholinergic stimulant

  10. Somatostatin modulates cholinergic neurotransmission in canine antral muscle

    International Nuclear Information System (INIS)

    Somatostatin has been shown to inhibit antral motility in vivo. To examine the effect of somatostatin on cholinergic neurotransmission in the canine antrum, we studied the mechanical response of and the release of [3H]acetylcholine from canine longitudinal antral muscle in response to substance P, gastrin 17, and electrical stimulation. In unstimulated tissues, somatostatin had a positive inotropic effect on spontaneous phasic contractions. In tissues stimulated with substance P and gastrin 17, but not with electrical stimulation, somatostatin inhibited the phasic inotropic response dose dependently. This inhibitory effect was abolished by indomethacin. Somatostatin stimulated the release of prostaglandin E2 radioimmunoreactivity, and prostaglandin E2 inhibited the release of [3H]acetylcholine induced by substance P and electrical stimulation. Somatostatin increased the release of [3H]acetylcholine from unstimulated tissues by a tetrodotoxin-sensitive mechanism but inhibited the release induced by substance P and electrical stimulation. These results suggest that somatostatin has a dual modulatory effect on cholinergic neutrotransmission in canine longitudinal antral muscle. This effect is excitatory in unstimulated tissues and inhibitory in stimulated tissues. The inhibitory effect is partially mediated by prostaglandins

  11. VTA GABA neurons modulate specific learning behaviours through the control of dopamine and cholinergic systems

    Directory of Open Access Journals (Sweden)

    Meaghan C Creed

    2014-01-01

    Full Text Available The mesolimbic reward system is primarily comprised of the ventral tegmental area (VTA and the nucleus accumbens (NAc as well as their afferent and efferent connections. This circuitry is essential for learning about stimuli associated with motivationally-relevant outcomes. Moreover, addictive drugs affect and remodel this system, which may underlie their addictive properties. In addition to DA neurons, the VTA also contains approximately 30% ɣ-aminobutyric acid (GABA neurons. The task of signalling both rewarding and aversive events from the VTA to the NAc has mostly been ascribed to DA neurons and the role of GABA neurons has been largely neglected until recently. GABA neurons provide local inhibition of DA neurons and also long-range inhibition of projection regions, including the NAc. Here we review studies using a combination of in vivo and ex vivo electrophysiology, pharmacogenetic and optogenetic manipulations that have characterized the functional neuroanatomy of inhibitory circuits in the mesolimbic system, and describe how GABA neurons of the VTA regulate reward and aversion-related learning. We also discuss pharmacogenetic manipulation of this system with benzodiazepines (BDZs, a class of addictive drugs, which act directly on GABAA receptors located on GABA neurons of the VTA. The results gathered with each of these approaches suggest that VTA GABA neurons bi-directionally modulate activity of local DA neurons, underlying reward or aversion at the behavioural level. Conversely, long-range GABA projections from the VTA to the NAc selectively target cholinergic interneurons (CINs to pause their firing and temporarily reduce cholinergic tone in the NAc, which modulates associative learning. Further characterization of inhibitory circuit function within and beyond the VTA is needed in order to fully understand the function of the mesolimbic system under normal and pathological conditions.

  12. Effects of Maternal Choline Supplementation on the Septohippocampal Cholinergic System in the Ts65Dn Mouse Model of Down Syndrome.

    Science.gov (United States)

    Kelley, Christy M; Ash, Jessica A; Powers, Brian E; Velazquez, Ramon; Alldred, Melissa J; Ikonomovic, Milos D; Ginsberg, Stephen D; Strupp, Barbara J; Mufson, Elliott J

    2016-01-01

    Down syndrome (DS), caused by trisomy of chromosome 21, is marked by intellectual disability (ID) and early onset of Alzheimer's disease (AD) neuropathology including hippocampal cholinergic projection system degeneration. Here we determined the effects of age and maternal choline supplementation (MCS) on hippocampal cholinergic deficits in Ts65Dn mice compared to 2N mice sacrificed at 6-8 and 14-18 months of age. Ts65Dn mice and disomic (2N) littermates sacrificed at ages 6-8 and 14-18 mos were used for an aging study and Ts65Dn and 2N mice derived from Ts65Dn dams were maintained on either a choline-supplemented or a choline-controlled diet (conception to weaning) and examined at 14-18 mos for MCS studies. In the latter, mice were behaviorally tested on the radial arm Morris water maze (RAWM) and hippocampal tissue was examined for intensity of choline acetyltransferase (ChAT) immunoreactivity. Hippocampal ChAT activity was evaluated in a separate cohort. ChAT-positive fiber innervation was significantly higher in the hippocampus and dentate gyrus in Ts65Dn mice compared with 2N mice, independent of age or maternal diet. Similarly, hippocampal ChAT activity was significantly elevated in Ts65Dn mice compared to 2N mice, independent of maternal diet. A significant increase with age was seen in hippocampal cholinergic innervation of 2N mice, but not Ts65Dn mice. Degree of ChAT intensity correlated negatively with spatial memory ability in unsupplemented 2N and Ts65Dn mice, but positively in MCS 2N mice. The increased innervation produced by MCS appears to improve hippocampal function, making this a therapy that may be exploited for future translational approaches in human DS. PMID:26391045

  13. Boosting Wigner's nj-symbols

    CERN Document Server

    Speziale, Simone

    2016-01-01

    We study the SL(2,C) Clebsch-Gordan coefficients appearing in the lorentzian EPRL spin foam amplitudes for loop quantum gravity. We show how the amplitudes decompose into SU(2) nj-symbols at the vertices and integrals over boosts at the edges. The integrals define edge amplitudes that can be evaluated analytically using and adapting results in the literature, leading to a pure state sum model formulation. This procedure introduces virtual representations which, in a manner reminiscent to virtual momenta in Feynman amplitudes, are off-shell of the simplicity constraints present in the theory, but with the integrands that peak at the on-shell values. We point out some properties of the edge amplitudes which are helpful for numerical and analytical evaluations of spin foam amplitudes, and suggest among other things a simpler model useful for calculations of certain lowest order amplitudes. As an application, we estimate the large spin scaling behaviour of the simpler model, on a closed foam with all 4-valent edg...

  14. Avoiding Anemia: Boost Your Red Blood Cells

    Science.gov (United States)

    ... link, please review our exit disclaimer . Subscribe Avoiding Anemia Boost Your Red Blood Cells If you’re ... and sluggish, you might have a condition called anemia. Anemia is a common blood disorder that many ...

  15. Anemia Boosts Stroke Death Risk, Study Finds

    Science.gov (United States)

    ... page: https://medlineplus.gov/news/fullstory_160476.html Anemia Boosts Stroke Death Risk, Study Finds Blood condition ... 2016 (HealthDay News) -- Older stroke victims suffering from anemia -- a lack of red blood cells -- may have ...

  16. Riemann curvature of a boosted spacetime geometry

    CERN Document Server

    Battista, Emmanuele; Scudellaro, Paolo; Tramontano, Francesco

    2014-01-01

    The ultrarelativistic boosting procedure had been applied in the literature to map the metric of Schwarzschild-de Sitter spacetime into a metric describing de Sitter spacetime plus a shock-wave singularity located on a null hypersurface. This paper evaluates the Riemann curvature tensor of the boosted Schwarzschild-de Sitter metric by means of numerical calculations, which make it possible to reach the ultrarelativistic regime gradually by letting the boost velocity approach the speed of light. Thus, for the first time in the literature, the singular limit of curvature through Dirac's delta distribution and its derivatives is numerically evaluated for this class of spacetimes. Eventually, the analysis of the Kteschmann invariant and the geodesic equation show that the spacetime possesses a scalar curvature singularity within a 3-sphere and it is possible to define what we here call boosted horizon, a sort of elastic wall where all particles are surprisingly pushed away, as numerical analysis demonstrates. Thi...

  17. On the generator of Lorentz boost

    Institute of Scientific and Technical Information of China (English)

    Wang Zhi-Yong; Xiong Cai-Dong

    2006-01-01

    Traditionally, the theory related to the spatial angular momentum has been studied completely, while the investigation in the generator of Lorentz boost is inadequate. This paper shows that the generator of Lorentz boost has a nontrivial physical significance: it endows a charged system with an electric moment, and has an important significance for the electrical manipulations of electron spin in spintronics. An alternative treatment and interpretation for the traditional Darwin term and spin-orbit coupling are given.

  18. Internationalization of Boost Juice to Malaysia

    OpenAIRE

    Jane L. Menzies; Stuart C. Orr

    2014-01-01

    This case describes the process that the Australian juice retail chain, Boost Juice, has used to internationalize to Malaysia. The main objective of this case is to demonstrate good practice in regard to internationalization. The case provides the background of the juice bar industry in Malaysia and determines that it is an attractive market for new start-up juice bars. An analysis of Boost Juice's capability determined that the company utilized the skills of its staff, product innovations, b...

  19. Novel Intrusion Detection using Probabilistic Neural Network and Adaptive Boosting

    CERN Document Server

    Tran, Tich Phuoc; Tran, Dat; Nguyen, Cuong Duc

    2009-01-01

    This article applies Machine Learning techniques to solve Intrusion Detection problems within computer networks. Due to complex and dynamic nature of computer networks and hacking techniques, detecting malicious activities remains a challenging task for security experts, that is, currently available defense systems suffer from low detection capability and high number of false alarms. To overcome such performance limitations, we propose a novel Machine Learning algorithm, namely Boosted Subspace Probabilistic Neural Network (BSPNN), which integrates an adaptive boosting technique and a semi parametric neural network to obtain good tradeoff between accuracy and generality. As the result, learning bias and generalization variance can be significantly minimized. Substantial experiments on KDD 99 intrusion benchmark indicate that our model outperforms other state of the art learning algorithms, with significantly improved detection accuracy, minimal false alarms and relatively small computational complexity.

  20. Novel Intrusion Detection using Probabilistic Neural Network and Adaptive Boosting

    Directory of Open Access Journals (Sweden)

    Tich Phuoc Tran

    2009-10-01

    Full Text Available This article applies Machine Learning techniques to solve Intrusion Detection problems withincomputer networks. Due to complex and dynamic nature of computer networks and hacking techniques, detecting malicious activities remains a challenging task for security experts, that is, currently available defense systems suffer from low detection capability and high number of false alarms. To overcome such performance limitations, we propose a novel Machine Learning algorithm, namely Boosted Subspace Probabilistic Neural Network (BSPNN, which integrates an adaptive boosting technique and a semi-parametric neural network to obtain good trade-off between accuracy and generality. As the result, learning bias and generalization variance can be significantly minimized. Substantial experiments on KDD-99 intrusion benchmark indicate that our model outperforms other state-of-the-art learning algorithms, with significantly improved detection accuracy, minimal false alarms and relatively small computational complexity.

  1. Deletion of neurturin impairs development of cholinergic nerves and heart rate control in postnatal mouse hearts.

    Science.gov (United States)

    Downs, Anthony M; Jalloh, Hawa B; Prater, Kayla J; Fregoso, Santiago P; Bond, Cherie E; Hampton, Thomas G; Hoover, Donald B

    2016-05-01

    The neurotrophic factor neurturin is required for normal cholinergic innervation of adult mouse heart and bradycardic responses to vagal stimulation. Our goals were to determine effects of neurturin deletion on development of cardiac chronotropic and dromotropic functions, vagal baroreflex response, and cholinergic nerve density in nodal regions of postnatal mice. Experiments were performed on postnatal C57BL/6 wild-type (WT) and neurturin knockout (KO) mice. Serial electrocardiograms were recorded noninvasively from conscious pups using an ECGenie apparatus. Mice were treated with atenolol to evaluate and block sympathetic effects on heart rate (HR) and phenylephrine (PE) to stimulate the baroreflex. Immunohistochemistry was used to label cholinergic nerves in paraffin sections. WT and KO mice showed similar age-dependent increases in HR and decreases in PR interval between postnatal days (P) 2.5 and 21. Treatment with atenolol reduced HR significantly in WT and KO pups at P7.5. PE caused a reflex bradycardia that was significantly smaller in KO pups. Cholinergic nerve density was significantly less in nodal regions of P7.5 KO mice. We conclude that cholinergic nerves have minimal influence on developmental changes in HR and PR, QRS, and QTc intervals in mouse pups. However, cholinergic nerves mediate reflex bradycardia by 1 week postnatally. Deletion of neurturin impairs cholinergic innervation of the heart and the vagal efferent component of the baroreflex early during postnatal development. PMID:27162260

  2. Effect of voluntary running on adult hippocampal neurogenesis in cholinergic lesioned mice

    Directory of Open Access Journals (Sweden)

    Dawe Gavin S

    2009-06-01

    Full Text Available Abstract Background Cholinergic neuronal dysfunction of the basal forebrain is observed in patients with Alzheimer's disease and dementia, and has been linked to decreased neurogenesis in the hippocampus, a region involved in learning and memory. Running is a robust inducer of adult hippocampal neurogenesis. This study aims to address the effect of running on hippocampal neurogenesis in lesioned mice, where septohippocampal cholinergic neurones have been selectively eliminated in the medial septum and diagonal band of Broca of the basal forebrain by infusion of mu-p75-saporin immunotoxin. Results Running increased the number of newborn cells in the dentate gyrus of the hippocampus in cholinergic denervated mice compared to non-lesioned mice 24 hours after injection of bromodeoxyuridine (BrdU. Although similar levels of surviving cells were present in cholinergic depleted animals and their respective controls four weeks after injection of BrdU, the majority of progenitors that proliferate in response to the initial period of running were not able to survive beyond one month without cholinergic input. Despite this, the running-induced increase in the number of surviving neurones was not affected by cholinergic depletion. Conclusion The lesion paradigm used here models aspects of the cholinergic deficits associated with Alzheimer's Disease and aging. We showed that running still increased the number of newborn cells in the adult hippocampal dentate gyrus in this model of neurodegenerative disease.

  3. Boosted Jets at the LHC

    Science.gov (United States)

    Larkoski, Andrew

    2015-04-01

    Jets are collimated streams of high-energy particles ubiquitous at any particle collider experiment and serve as proxy for the production of elementary particles at short distances. As the Large Hadron Collider at CERN continues to extend its reach to ever higher energies and luminosities, an increasingly important aspect of any particle physics analysis is the study and identification of jets, electroweak bosons, and top quarks with large Lorentz boosts. In addition to providing a unique insight into potential new physics at the tera-electron volt energy scale, high energy jets are a sensitive probe of emergent phenomena within the Standard Model of particle physics and can teach us an enormous amount about quantum chromodynamics itself. Jet physics is also invaluable for lower-level experimental issues including triggering and background reduction. It is especially important for the removal of pile-up, which is radiation produced by secondary proton collisions that contaminates every hard proton collision event in the ATLAS and CMS experiments at the Large Hadron Collider. In this talk, I will review the myriad ways that jets and jet physics are being exploited at the Large Hadron Collider. This will include a historical discussion of jet algorithms and the requirements that these algorithms must satisfy to be well-defined theoretical objects. I will review how jets are used in searches for new physics and ways in which the substructure of jets is being utilized for discriminating backgrounds from both Standard Model and potential new physics signals. Finally, I will discuss how jets are broadening our knowledge of quantum chromodynamics and how particular measurements performed on jets manifest the universal dynamics of weakly-coupled conformal field theories.

  4. The involvement of cholinergic neurons in the spreading of tau pathology

    Directory of Open Access Journals (Sweden)

    Diana eSimon

    2013-06-01

    Full Text Available Long time ago, it was described the selective loss of cholinergic neurons during the development of Alzheimer disease. Recently, it has been suggested that tau protein may play a role in that loss of cholinergic neurons through a mechanism involving the interaction of extracellular tau with M1/M3 muscarinic receptors present in the cholinergic neurons. This interaction between tau and muscarinic receptors may be a way, although not the only one, to explain the spreading of tau pathology occurring in Alzheimer disease.

  5. Tolerance of nestin+ cholinergic neurons in the basal forebrain against colchicine-induced cytotoxicity

    Institute of Scientific and Technical Information of China (English)

    Jing Yu; Kaihua Guo; Dongpei Li; Jinhai Duan; Juntao Zou; Junhua Yang; Zhibin Yao

    2011-01-01

    In the present study we injected colchicine into the lateral ventricle of Sprague-Dawley rats to investigate the effects of colchicine on the number of different-type neurons in the basal forebrain and to search for neurons resistant to injury. After colchicine injection, the number of nestin+ cholinergic neurons was decreased at 1 day, but increased at 3 days and peaked at 14-28 days. The quantity of nestin- cholinergic neurons, parvalbumin-positive neurons and choline acetyl transferase-positive neurons decreased gradually. Our results indicate that nestin+ cholinergic neurons possess better tolerance to colchicine-induced neurotoxicity.

  6. Two types of functionally different GABAA receptors mediate GABA modulation of cholinergic transmission in cat terminal ileum.

    Science.gov (United States)

    Radomirov, R; Pencheva, N

    1995-08-01

    1. The effects of GABA (1 microM-2 mM) on longitudinally or circularly oriented organ bath preparations of cat terminal ileum consisted of a relaxation phase with an inhibition of the rhythmic spontaneous phasic contractions, followed by a phase of contractions characterized by an elevation in basal tone and an increase in amplitude of the spontaneous phasic contractions. 2. Muscimol (100 microM), but not baclofen (100 microM), mimicked the relaxation phase of the response to applied GABA (100 microM) in all tissue preparations. In addition, muscimol induced a phase of contractile activity in the circular muscle layer whilst baclofen exerted a 'GABA-like' contractile effect on the longitudinal muscle layer. Bicuculline (30 microM) or picrotoxinin (30 microM) antagonized the GABA- or muscimol-induced relaxations in all preparations and decreased the GABA- but not the baclofen-induced contractions of the longitudinal muscle layer. 3. Tetrodotoxin (0.5 microM) or atropine (0.1 microM) prevented the bicuculline-sensitive phases of the GABA or muscimol effects on both muscle layers but not the contractile effect of baclofen on the longitudinal muscle layer. 4. The bicuculline-sensitive phases of the GABA effect on both muscle layers were almost completely eliminated by 1 nM pirenzepine. At this concentration pirenzepine did not affect the electrically-evoked cholinergic twitch contractions or contractile responses to applied acetylcholine of both muscle layers. 5. During electrically-evoked cholinergic twitch contractions of both muscle layers, GABA (100 microM) had an inhibitory effect. The inhibition occurred in the presence of pirenzepine (1 nM) but not of bicuculline (30 microM). 6. It is suggested that two types of functionally different bicuculline-sensitive GABAA receptors mediate an exitatory presynaptic and an inhibitory prejunctional action of GABA on the cholinergic transmission in cat terminal ileum. PMID:8576270

  7. Chemical and radiological effects of chronic ingestion of uranium in the rat brain: biochemical impairment of dopaminergic, serotonergic and cholinergic neuro-transmissions

    International Nuclear Information System (INIS)

    Uranium is an environmental ubiquitous metal-trace element. It has both chemical and radiological toxicity. After chronic ingestion, uranium can distribute in any part of the body and accumulate in the brain. The aims of this study was 1) to determine and estimate the effects of uranium on dopaminergic, serotoninergic and cholinergic systems and 2) to measure the uranium amount in the brain, after chronic exposure by ingestion of depleted (D.U.) or enriched (E.U.) uranium during 1.5 to 18 months at 40 mg.L-1 (40 ppm) in different rat brain areas. At any time of exposure, the results show that both the neurotransmission alterations and the uranium brain accumulation were moderate, area specific, time-evolutive and depended on uranium specific activity. After D.U. exposure, monoamine perturbations are chronic and progressive. On the contrary, monoamine alterations occurred only after long term of E.U. exposure. These mono-aminergic modifications are not always dependent on uranium accumulation in brain areas. Moreover, although the cholinergic system was not affected at both 1.5 and 9 months of D.U. exposure, the alteration of ChE activity after E.U. exposure are both dependent on uranium accumulation in brain areas and on uranium specific activity. After E.U. exposure, cholinergic modification and uranium accumulation in hippocampus could partially explain the short-term memory disturbances which have been previously reported. (author)

  8. Central cholinergic control of vasopressin release in conscious rats

    International Nuclear Information System (INIS)

    Intracerebroventricular (icv) administration of carbachol into conscious rats evoked a substantial increase in vasopressin secretion and blood pressure in a dose-dependent manner. These effects were blocked by pretreatment with the muscarinic blocker, atropine (10 μg icv), but not by the nicotinic blocker, hexamethonium (10 μg icv). Hexamethonium did, however, block the increase in blood pressure, the decrease in heart rate, and they very small elevation in the plasma vasopressin concentration induced by nicotine (10 μg icv). These results indicate that stimulation of either central nicotinic or muscarinic receptors can affect the cardiovascular system and suggest that the cholinergic stimulation of vasopressin secretion may involve primarily muscarinic receptors in the conscious rat

  9. Network burst dynamics under heterogeneous cholinergic modulation of neural firing properties and heterogeneous synaptic connectivity.

    Science.gov (United States)

    Knudstrup, Scott; Zochowski, Michal; Booth, Victoria

    2016-05-01

    The characteristics of neural network activity depend on intrinsic neural properties and synaptic connectivity in the network. In brain networks, both of these properties are critically affected by the type and levels of neuromodulators present. The expression of many of the most powerful neuromodulators, including acetylcholine (ACh), varies tonically and phasically with behavioural state, leading to dynamic, heterogeneous changes in intrinsic neural properties and synaptic connectivity properties. Namely, ACh significantly alters neural firing properties as measured by the phase response curve in a manner that has been shown to alter the propensity for network synchronization. The aim of this simulation study was to build an understanding of how heterogeneity in cholinergic modulation of neural firing properties and heterogeneity in synaptic connectivity affect the initiation and maintenance of synchronous network bursting in excitatory networks. We show that cells that display different levels of ACh modulation have differential roles in generating network activity: weakly modulated cells are necessary for burst initiation and provide synchronizing drive to the rest of the network, whereas strongly modulated cells provide the overall activity level necessary to sustain burst firing. By applying several quantitative measures of network activity, we further show that the existence of network bursting and its characteristics, such as burst duration and intraburst synchrony, are dependent on the fraction of cell types providing the synaptic connections in the network. These results suggest mechanisms underlying ACh modulation of brain oscillations and the modulation of seizure activity during sleep states. PMID:26869313

  10. Changes in the cholinergic system of rat sciatic nerve and skeletal muscle following suspension induced disuse

    Science.gov (United States)

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

    1984-01-01

    Muscle disused induced changes in the cholinergic system of sciatic nerve, slow twitch soleus (SOL) and fast twitch extensor digitorum longus (EDL) muscle were studied in rats. Rats with hindlimbs suspended for 2 to 3 weeks showed marked elevation in the activity of choline acetyltransferase (ChAT) in sciatic nerve (38%), in SOL (108%) and in EDL (67%). Acetylcholinesterase (AChE) activity in SOL increased by 163% without changing the molecular forms pattern of 4S, 10S, 12S, and 16S. No significant changes in activity and molecular forms pattern of AChE were seen in EDL or in AChE activity of sciatic nerve. Nicotinic receptor binding of 3H-acetylcholine was increased in both muscles. When measured after 3 weeks of hindlimb suspension the normal distribution of type 1 fibers in SOL was reduced and a corresponding increase in type IIa and IIb fibers is seen. In EDL no significant change in fiber proportion is observed. Muscle activity, such as loadbearing, appears to have a greater controlling influence on the characteristics of the slow twitch SOL muscle than upon the fast twitch EDL muscle.

  11. Cholinergic and non-cholinergic projections from the pedunculopontine and laterodorsal tegmental nuclei to the medial geniculate body in guinea pigs

    Directory of Open Access Journals (Sweden)

    Susan D Motts

    2010-10-01

    Full Text Available The midbrain tegmentum is the source of cholinergic innervation of the thalamus and has been associated with arousal and control of the sleep/wake cycle. In general, the innervation arises bilaterally from the pedunculopontine tegmental nucleus (PPT and the laterodorsal tegmental nucleus (LDT. While this pattern has been observed for many thalamic nuclei, a projection from the LDT to the medial geniculate body (MG has been questioned in some species. We combined retrograde tracing with immunohistochemistry for choline acetyltransferase (ChAT to identify cholinergic projections from the brainstem to the MG in guinea pigs. Double-labeled cells (retrograde and immunoreactive for ChAT were found in both the PPT (74% and the LDT (26%. In both nuclei, double-labeled cells were more numerous on the ipsilateral side. About half of the retrogradely labeled cells were immunonegative, suggesting they are non-cholinergic. The distribution of these immunonegative cells was similar to that of the immunopositive ones: more were in the PPT than the LDT and more were on the ipsilateral than the contralateral side. The results indicate that both the PPT and the LDT project to the MG, and suggest that both cholinergic and non-cholinergic cells contribute substantially to these projections.

  12. Effects of proton irradiation of the lumbar intumescence on intra-axonal transport of acetylcholine and cholinergic enzymes in rat sciatic nerve

    International Nuclear Information System (INIS)

    The content and intra-axonal transport of acetylcholine (ACh) and the cholinergic enzymes cholineacetyl-transferase (CAT) and ACh-esterase (AChE) in sciatic nerve were investigated in rats following single dose proton irradiation of the lumbar intumescence of the spinal cord with 60 Gy or 200 Gy. One, 7 or 30 days after irradiation nerve-crush operations were performed 12 hours before killing and the levels of ACh and enzyme activities in nerve segments relative to the crushes were estimated by biologic (ACh) to chemical (enzyme) methods. The results indicate that alterations in intra-neuronal dynamics of ACh and related enzymes are not a major cause for the development of neurologic symptoms of the motor system after irradiation, and that descending myelinated axons are of minor importance for the regulation of cholinergic substances in rat motor nerves. (Auth.)

  13. The α7-nicotinic receptor is upregulated in immune cells from HIV-seropositive women: consequences to the cholinergic anti-inflammatory response.

    Science.gov (United States)

    Delgado-Vélez, Manuel; Báez-Pagán, Carlos A; Gerena, Yamil; Quesada, Orestes; Santiago-Pérez, Laura I; Capó-Vélez, Coral M; Wojna, Valerie; Meléndez, Loyda; León-Rivera, Rosiris; Silva, Walter; Lasalde-Dominicci, José A

    2015-12-01

    Antiretroviral therapy partially restores the immune system and markedly increases life expectancy of HIV-infected patients. However, antiretroviral therapy does not restore full health. These patients suffer from poorly understood chronic inflammation that causes a number of AIDS and non-AIDS complications. Here we show that chronic inflammation in HIV+ patients may be due to the disruption of the cholinergic anti-inflammatory pathway by HIV envelope protein gp120IIIB. Our results demonstrate that HIV gp120IIIB induces α7 nicotinic acetylcholine receptor (α7) upregulation and a paradoxical proinflammatory phenotype in macrophages, as activation of the upregulated α7 is no longer capable of inhibiting the release of proinflammatory cytokines. Our results demonstrate that disruption of the cholinergic-mediated anti-inflammatory response can result from an HIV protein. Collectively, these findings suggest that HIV tampering with a natural strategy to control inflammation could contribute to a crucial, unresolved problem of HIV infection: chronic inflammation. PMID:26719799

  14. Regulation of Prostate Development and Benign Prostatic Hyperplasia by Autocrine Cholinergic Signaling via Maintaining the Epithelial Progenitor Cells in Proliferating Status

    Directory of Open Access Journals (Sweden)

    Naitao Wang

    2016-05-01

    Full Text Available Regulation of prostate epithelial progenitor cells is important in prostate development and prostate diseases. Our previous study demonstrated a function of autocrine cholinergic signaling (ACS in promoting prostate cancer growth and castration resistance. However, whether or not such ACS also plays a role in prostate development is unknown. Here, we report that ACS promoted the proliferation and inhibited the differentiation of prostate epithelial progenitor cells in organotypic cultures. These results were confirmed by ex vivo lineage tracing assays and in vivo renal capsule recombination assays. Moreover, we found that M3 cholinergic receptor (CHRM3 was upregulated in a large subset of benign prostatic hyperplasia (BPH tissues compared with normal tissues. Activation of CHRM3 also promoted the proliferation of BPH cells. Together, our findings identify a role of ACS in maintaining prostate epithelial progenitor cells in the proliferating state, and blockade of ACS may have clinical implications for the management of BPH.

  15. Impairment of ATP hydrolysis decreases adenosine A1 receptor tonus favoring cholinergic nerve hyperactivity in the obstructed human urinary bladder.

    Science.gov (United States)

    Silva-Ramos, M; Silva, I; Faria, M; Magalhães-Cardoso, M T; Correia, J; Ferreirinha, F; Correia-de-Sá, P

    2015-12-01

    This study was designed to investigate whether reduced adenosine formation linked to deficits in extracellular ATP hydrolysis by NTPDases contributes to detrusor neuromodulatory changes associated with bladder outlet obstruction in men with benign prostatic hyperplasia (BPH). The kinetics of ATP catabolism and adenosine formation as well as the role of P1 receptor agonists on muscle tension and nerve-evoked [(3)H]ACh release were evaluated in mucosal-denuded detrusor strips from BPH patients (n = 31) and control organ donors (n = 23). The neurogenic release of ATP and [(3)H]ACh was higher (P bladders. Relaxation of detrusor contractions induced by acetylcholine required 30-fold higher concentrations of adenosine. Despite VAChT-positive cholinergic nerves exhibiting higher A(1) immunoreactivity in BPH bladders, the endogenous adenosine tonus revealed by adenosine deaminase is missing. Restoration of A1 inhibition was achieved by favoring (1) ATP hydrolysis with apyrase (2 U mL(-1)) or (2) extracellular adenosine accumulation with dipyridamole or EHNA, as these drugs inhibit adenosine uptake and deamination, respectively. In conclusion, reduced ATP hydrolysis leads to deficient adenosine formation and A(1) receptor-mediated inhibition of cholinergic nerve activity in the obstructed human bladder. Thus, we propose that pharmacological manipulation of endogenous adenosine levels and/or A(1) receptor activation might be useful to control bladder overactivity in BPH patients. PMID:26521170

  16. C. elegans dopaminergic D2-like receptors delimit recurrent cholinergic-mediated motor programs during a goal-oriented behavior.

    Directory of Open Access Journals (Sweden)

    Paola Correa

    Full Text Available Caenorhabditis elegans male copulation requires coordinated temporal-spatial execution of different motor outputs. During mating, a cloacal circuit consisting of cholinergic sensory-motor neurons and sex muscles maintains the male's position and executes copulatory spicule thrusts at his mate's vulva. However, distinct signaling mechanisms that delimit these behaviors to their proper context are unclear. We found that dopamine (DA signaling directs copulatory spicule insertion attempts to the hermaphrodite vulva by dampening spurious stimulus-independent sex muscle contractions. From pharmacology and genetic analyses, DA antagonizes stimulatory ACh signaling via the D2-like receptors, DOP-2 and DOP-3, and Gα(o/i proteins, GOA-1 and GPA-7. Calcium imaging and optogenetics suggest that heightened DA-expressing ray neuron activities coincide with the cholinergic cloacal ganglia function during spicule insertion attempts. D2-like receptor signaling also attenuates the excitability of additional mating circuits to reduce the duration of mating attempts with unproductive and/or inappropriate partners. This suggests that, during wild-type mating, simultaneous DA-ACh signaling modulates the activity threshold of repetitive motor programs, thus confining the behavior to the proper situational context.

  17. Dysregulated cholinergic network as a novel biomarker of poor prognostic in patients with head and neck squamous cell carcinoma

    International Nuclear Information System (INIS)

    In airways, a proliferative effect is played directly by cholinergic agonists through nicotinic and muscarinic receptors activation. How tumors respond to aberrantly activated cholinergic signalling is a key question in smoking-related cancer. This research was addressed to explore a possible link of cholinergic signalling changes with cancer biology. Fifty-seven paired pieces of head and neck squamous cell carcinoma (HNSCC) and adjacent non-cancerous tissue (ANCT) were compared for their mRNA levels for ACh-related proteins and ACh-hydrolyzing activity. The measurement in ANCT of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activities (5.416 ± 0.501 mU/mg protein and 6.350 ± 0.599 mU/mg protein, respectively) demonstrated that upper respiratory tract is capable of controlling the availability of ACh. In HNSCC, AChE and BChE activities dropped to 3.584 ± 0.599 mU/mg protein (p = 0.002) and 3.965 ± 0.423 mU/mg protein (p < 0.001). Moreover, tumours with low AChE activity and high BChE activity were associated with shorter patient overall survival. ANCT and HNSCC differed in mRNA levels for AChE-T, α3, α5, α9 and β2 for nAChR subunits. Tobacco exposure had a great impact on the expression of both AChE-H and AChE-T mRNAs. Unaffected and cancerous pieces contained principal AChE dimers and BChE tetramers. The lack of nerve-born PRiMA-linked AChE agreed with pathological findings on nerve terminal remodelling and loss in HNSCC. Our results suggest that the low AChE activity in HNSCC can be used to predict survival in patients with head and neck cancer. So, the ChE activity level can be used as a reliable prognostic marker. The online version of this article (doi:10.1186/s12885-015-1402-y) contains supplementary material, which is available to authorized users

  18. Comparative Study of 4-Switch Buck-Boost Controller and Regular Buck-Boost

    Directory of Open Access Journals (Sweden)

    Taufik Taufik

    2011-01-01

    Full Text Available A very important characteristic that dc-dc converters require is the ability to efficiently regulate an output voltage with a wide ranging value of input voltages. A recently developed solution to this requirement is a synchronous 4-Switch Buck-Boost controller developed by Linear Technology. The Linear Technology’s LTC3780 controller chip enables  the adoption of a 4-Switch switching topology as opposed to the traditional single-switch Buck-Boost topology. In this paper, the LTC3780’s 4-Switch BuckBoost topology is analyzed and its performance is compared against those of the regular single-switch Buck-Boost topology. Results from computer simulations demonstrate the benefits of using the 4-switch approach than the conventional buck-boost method.

  19. Effect of bilobalide B on cholinergic hippocampal neurons exposed to cholesterol and apoliprotein E4

    Institute of Scientific and Technical Information of China (English)

    Xijuan Jiang; Bin Lu; Yingchang Fan

    2008-01-01

    BACKGROUND: Extracts of ginkgo biloba leaves have been reported to improve nerve function and activity in Alzheimer's disease, which is associated with reduced secretion of cholinergic neurotransmitter in hippocampal neurons.OBJECTIVE: To validate the protective effect of bilobalide B against in vitro injury of cholinergic neurons of the hippocampus induced by combined cholesterol and apoE4DESIGN, TIME AND SETTING: This randomized, controlled animal experiment was performed in the Pathology Laboratory, Tianjin University of Traditional Chinese Medicine from July 2003 to July 2006.MATERIALS: Neonatal Wistar rats, 1-day-old, both male and female, and mean body mass of 5g were selected for this study. Cholesterol and apolipoprotein E4 (apoE4) were purchased from Sigma Company (USA), bilobalide B was purchased from Tianjin Zhongyi Pharmaceutical Factory, batch number 20050312.METHODS: Hippocampal neurons were divided into three groups; a normal control group (routinely added media), a model group (exposed to media containing 40mg/L cholesterol and 30mg/L apoE4 for 24 hours) and a bilobalide B group (exposed to media containing 160mg/L bilobalide B for 16 hours, and then with addition of 40mg/L cholesterol and 30mg/L apoE4 for an additional 24 hours).MAIN OUTCOME MEASURES: Levels of acetylcholine (ACh) and activity of acetylcholinesterase (AChE) and choline acetyltransferase (ChAT) in hippocampal neurons were determined by microdosage hydroxylamine colorimetry, hydroxylamine colorimetry and radiological chemistry, respectively.RESULTS: The ACh level was significantly lower in the model group than that in the normal control group (P0.05). Activity of ChAT was significantly lower in the model group than in the normal control group (P<0.01), while the activity was significantly higher in the bilobalide B group than in the model group (P<0.05).CONCLUSION: Bilobalide B can enhance the ACh level of hippocampal neurons damaged by combined cholesterol and apoE4, by promoting

  20. Liang-Ge-San, a classic traditional Chinese medicine formula, protects against lipopolysaccharide-induced inflammation through cholinergic anti-inflammatory pathway.

    Science.gov (United States)

    Liu, Jun-Shan; Wei, Xi-Duan; Lu, Zi-Bin; Xie, Pei; Zhou, Hong-Ling; Chen, Yu-Yao; Ma, Jia-Mei; Yu, Lin-Zhong

    2016-04-19

    Liang-Ge-San (LGS) is a classic formula in traditional Chinese medicine, which is widely used to treat acute lung injury (ALI), pharyngitis and amygdalitis in clinic. However, the underlying mechanisms remain poorly defined. In this study, we discovered that LGS exerted potent anti-inflammatory effects in lipopolysaccharide (LPS)-induced inflammation. We found that LGS significantly depressed the production of IL-6 and TNF-α in LPS-stimulated RAW 264.7 macrophage cells. The degradation and phosphorylation of IκBα and the nuclear translocation of NF-κB p65 were also inhibited. Moreover, LGS activated α7 nicotinic cholinergic receptor (α7nAchR). The blockage of α7nAchR by selective inhibitor methyllycaconitine (MLA) or α7nAchR siRNA attenuated the inhibitory effects of LGS on IκBα, NF-κB p65, IL-6 and TNF-α. Critically, LGS significantly inhibited inflammation in LPS-induced ALI rats through the activation of NF-κB signaling pathway. However, these protective effects could be counteracted by the treatment of MLA. Taken together, we first demonstrated anti-inflammatory effects of LGS both in vitro and in vivo through cholinergic anti-inflammatory pathway. The study provides a rationale for the clinical application of LGS as an anti-inflammatory agent and supports the critical role of cholinergic anti-inflammatory pathway in inflammation. PMID:27034013

  1. Transplantation of cholinergic neural stem cells in a mouse model of Alzheimer's disease

    Institute of Scientific and Technical Information of China (English)

    WANG Qing-hua; XU Ru-xiang; Seigo Nagao

    2005-01-01

    @@ It is believed that the degeneration of cholinergic cells in the nucleus basalis of Meynert (NBM) and the loss of cortical cholinergic innervation cause dementia of Alzheimer's disease (AD).1 Currently available therapeutic interventions are mainly aimed at alleviating the cholinergic deficits. Unfortunately, these strategies do not prevent the disease, but instead offer limited symptomatic improvement.2 A recent study demonstrated that transplantation of in vitro expanded neural stem cells (NSCs) in an animal model of Parkinson's disease (PD) resulted in functional recovery of the animals to some extent,2 suggesting that such neural precursors might offer a useful future therapy for AD. In this study, we tried to find whether mouse embryonic stem (ES) cell derived cholinergic NSCs grafted in the prefrontal and parietal cortex have effects on the disruption of spatial memory following development of lesion in NBM.

  2. Concomitant boost radiotherapy in oropharynx carcinomas

    International Nuclear Information System (INIS)

    Fifty-five patients with resectable and unresectable oropharynx carcinomas were treated with concomitant boost radiotherapy. Forty-two of the patients (76%) had stages III-IV disease. Although none of the patients had undergone major surgery to the primary tumor, 11 had neck dissections prior to radiotherapy, and 19 (35%) received chemotherapy. The planned total tumor dose was 69.9 Gy, delivered over 5.5 weeks. During the last 3.5 weeks, a boost to the initial gross disease was delivered in 13 fractions of 1.5 Gy each, as a second daily fraction in a progressively accelerated schedule; the prescribed dose outside the boost volume thus was 50.4 Gy. Median follow-up for surviving patients was 31.5 months (range: 16-65 months). All patients but one completed the planned radiotherapy schedule. According to the RTOG scoring system, 48 patients (88%) presented with grades 3-4 acute toxicity. The rate of grades 3-4 late complications was 12%. At three years the actuarial locoregional control rate was 69.5% and overall survival was 60%. We conclude that this concomitant boost schedule is feasible and does not seem to be associated with an excess risk of late complications. Acute toxicity was higher in association with chemotherapy, but remained manageable. Although the oncological results appear encouraging, evaluation of the efficacy of concomitant boost schedules compared with conventionally fractionated irradiation with or without concomitant chemotherapy requires prospective randomized trials. (orig.)

  3. Concomitant boost radiotherapy in oropharynx carcinomas

    Energy Technology Data Exchange (ETDEWEB)

    Bieri, S.; Allal, A.S.; Kurtz, J.M. [Ospedale San Giovanni, Bellinzona (Switzerland). Dept. of Radiation Oncology; Dulguerov, P.; Lehmann, W. [Geneva Univ. Hospital (Switzerland). Div. of Head and Neck Surgery

    1998-12-31

    Fifty-five patients with resectable and unresectable oropharynx carcinomas were treated with concomitant boost radiotherapy. Forty-two of the patients (76%) had stages III-IV disease. Although none of the patients had undergone major surgery to the primary tumor, 11 had neck dissections prior to radiotherapy, and 19 (35%) received chemotherapy. The planned total tumor dose was 69.9 Gy, delivered over 5.5 weeks. During the last 3.5 weeks, a boost to the initial gross disease was delivered in 13 fractions of 1.5 Gy each, as a second daily fraction in a progressively accelerated schedule; the prescribed dose outside the boost volume thus was 50.4 Gy. Median follow-up for surviving patients was 31.5 months (range: 16-65 months). All patients but one completed the planned radiotherapy schedule. According to the RTOG scoring system, 48 patients (88%) presented with grades 3-4 acute toxicity. The rate of grades 3-4 late complications was 12%. At three years the actuarial locoregional control rate was 69.5% and overall survival was 60%. We conclude that this concomitant boost schedule is feasible and does not seem to be associated with an excess risk of late complications. Acute toxicity was higher in association with chemotherapy, but remained manageable. Although the oncological results appear encouraging, evaluation of the efficacy of concomitant boost schedules compared with conventionally fractionated irradiation with or without concomitant chemotherapy requires prospective randomized trials. (orig.)

  4. Positive Semidefinite Metric Learning with Boosting

    CERN Document Server

    Shen, Chunhua; Wang, Lei; Hengel, Anton van den

    2009-01-01

    The learning of appropriate distance metrics is a critical problem in image classification and retrieval. In this work, we propose a boosting-based technique, termed \\BoostMetric, for learning a Mahalanobis distance metric. One of the primary difficulties in learning such a metric is to ensure that the Mahalanobis matrix remains positive semidefinite. Semidefinite programming is sometimes used to enforce this constraint, but does not scale well. \\BoostMetric is instead based on a key observation that any positive semidefinite matrix can be decomposed into a linear positive combination of trace-one rank-one matrices. \\BoostMetric thus uses rank-one positive semidefinite matrices as weak learners within an efficient and scalable boosting-based learning process. The resulting method is easy to implement, does not require tuning, and can accommodate various types of constraints. Experiments on various datasets show that the proposed algorithm compares favorably to those state-of-the-art methods in terms of classi...

  5. Ultrastructural localization of cholinergic muscarinic receptors in rat brain cortical capillaries

    OpenAIRE

    Luiten, PGM; DEJONG, GI; VANDERZEE, EA; vanDijken, H; van Dijken, H.

    1996-01-01

    Cholinergic innervation of the cerebrovasculature is known to regulate vascular tone, perfusion rate and permeability of the microvascular wall. Notably the cholinergic innervation of cerebral capillaries is of interest since these capillaries form the blood-brain barrier. Although there is a general consensus as to the presence of nicotinic and muscarinic receptors in the domain of the capillary wall, their precise anatomical position is unknown. The subcellular localization of muscarinic re...

  6. Higher sensitivity to cadmium induced cell death of basal forebrain cholinergic neurons: A cholinesterase dependent mechanism

    International Nuclear Information System (INIS)

    Cadmium is an environmental pollutant, which is a cause of concern because it can be greatly concentrated in the organism causing severe damage to a variety of organs including the nervous system which is one of the most affected. Cadmium has been reported to produce learning and memory dysfunctions and Alzheimer like symptoms, though the mechanism is unknown. On the other hand, cholinergic system in central nervous system (CNS) is implicated on learning and memory regulation, and it has been reported that cadmium can affect cholinergic transmission and it can also induce selective toxicity on cholinergic system at peripheral level, producing cholinergic neurons loss, which may explain cadmium effects on learning and memory processes if produced on central level. The present study is aimed at researching the selective neurotoxicity induced by cadmium on cholinergic system in CNS. For this purpose we evaluated, in basal forebrain region, the cadmium toxic effects on neuronal viability and the cholinergic mechanisms related to it on NS56 cholinergic mourine septal cell line. This study proves that cadmium induces a more pronounced, but not selective, cell death on acetylcholinesterase (AChE) on cholinergic neurons. Moreover, MTT and LDH assays showed a dose dependent decrease of cell viability in NS56 cells. The ACh treatment of SN56 cells did not revert cell viability reduction induced by cadmium, but siRNA transfection against AChE partially reduced it. Our present results provide new understanding of the mechanisms contributing to the harmful effects of cadmium on the function and viability of neurons, and the possible relevance of cadmium in the pathogenesis of neurodegenerative diseases

  7. EEG sleep and the cholinergic REM induction test in anorexic and bulimic patients

    OpenAIRE

    Lauer, C.; Zulley, Jürgen; Krieg, J. C.; Riemann, D.; Berger, M

    1988-01-01

    The electroencephalographic (EEG) sleep of 20 anorexic patients, 10 bulimic patients, and 10 age-matched healthy controls was studied. In addition, six anorexic patients and six bulimic patients had a cholinergic rapid eye movement (REM) sleep induction test (RIT) performed with the cholinergic agent RS 86. The three samples showed no major differences in sleep patterns. The same held true when attention was focused on patients who additionally met DSM-III criteria for major depression. The R...

  8. Cholinergic-serotonergic imbalance contributes to cognitive and behavioral symptoms in Alzheimer's disease

    OpenAIRE

    Garcia-Alloza, M; Gil-Bea, F.J. (Francisco J.); Diez-Ariza, M. (Mónica); Chen, C. P.; Francis, P.T.; Lasheras, B.; Ramirez, M.J.

    2005-01-01

    Neuropsychiatric symptoms seen in Alzheimer's disease (AD) are not simply a consequence of neurodegeneration, but probably result from differential neurotransmitter alterations, which some patients are more at risk of than others. Therefore, the hypothesis of this study is that an imbalance between the cholinergic and serotonergic systems is related to cognitive symptoms and psychological syndromes of dementia (BPSD) in patients with AD. Cholinergic and serotonergic functions were assessed in...

  9. Coordinated regulation of cholinergic motor neuron traits through a conserved terminal selector gene

    OpenAIRE

    Kratsios, Paschalis; Stolfi, Alberto; Levine, Michael; Hobert, Oliver

    2011-01-01

    Cholinergic motor neurons are defined by the co-expression of a battery of genes which encode proteins that act sequentially to synthesize, package and degrade acetylcholine and reuptake its breakdown product, choline. How expression of these critical motor neuron identity determinants is controlled and coordinated is not understood. We show here that in the nematode Caenorhabditis elegans all members of the cholinergic gene battery, as well as many other markers of terminal motor neuron fate...

  10. Cholinergic systems are essential for late-stage maturation and refinement of motor cortical circuits.

    Science.gov (United States)

    Ramanathan, Dhakshin S; Conner, James M; Anilkumar, Arjun A; Tuszynski, Mark H

    2015-03-01

    Previous studies reported that early postnatal cholinergic lesions severely perturb early cortical development, impairing neuronal cortical migration and the formation of cortical dendrites and synapses. These severe effects of early postnatal cholinergic lesions preclude our ability to understand the contribution of cholinergic systems to the later-stage maturation of topographic cortical representations. To study cholinergic mechanisms contributing to the later maturation of motor cortical circuits, we first characterized the temporal course of cortical motor map development and maturation in rats. In this study, we focused our attention on the maturation of cortical motor representations after postnatal day 25 (PND 25), a time after neuronal migration has been accomplished and cortical volume has reached adult size. We found significant maturation of cortical motor representations after this time, including both an expansion of forelimb representations in motor cortex and a shift from proximal to distal forelimb representations to an extent unexplainable by simple volume enlargement of the neocortex. Specific cholinergic lesions placed at PND 24 impaired enlargement of distal forelimb representations in particular and markedly reduced the ability to learn skilled motor tasks as adults. These results identify a novel and essential role for cholinergic systems in the late refinement and maturation of cortical circuits. Dysfunctions in this system may constitute a mechanism of late-onset neurodevelopmental disorders such as Rett syndrome and schizophrenia. PMID:25505106

  11. Impairment of reward-related learning by cholinergic cell ablation in the striatum.

    Science.gov (United States)

    Kitabatake, Yasuji; Hikida, Takatoshi; Watanabe, Dai; Pastan, Ira; Nakanishi, Shigetada

    2003-06-24

    The striatum in the basal ganglia-thalamocortical circuitry is a key neural substrate that is implicated in motor balance and procedural learning. The projection neurons in the striatum are dynamically modulated by nigrostriatal dopaminergic input and intrastriatal cholinergic input. The role of intrastriatal acetylcholine (ACh) in learning behaviors, however, remains to be fully clarified. In this investigation, we examine the involvement of intrastriatal ACh in different categories of learning by selectively ablating the striatal cholinergic neurons with use of immunotoxin-mediated cell targeting. We show that selective ablation of cholinergic neurons in the striatum impairs procedural learning in the tone-cued T-maze memory task. Spatial delayed alternation in the T-maze learning test is also impaired by cholinergic cell elimination. In contrast, the deficit in striatal ACh transmission has no effect on motor learning in the rota-rod test or spatial learning in the Morris water-maze test or on contextual- and tone-cued conditioning fear responses. We also report that cholinergic cell elimination adaptively up-regulates nicotinic ACh receptors not only within the striatum but also in the cerebral cortex and substantia nigra. The present investigation indicates that cholinergic modulation in the local striatal circuit plays a pivotal role in regulation of neural circuitry involving reward-related procedural learning and working memory. PMID:12802017

  12. Lesions of the basal forebrain cholinergic system in mice disrupt idiothetic navigation.

    Directory of Open Access Journals (Sweden)

    Adam S Hamlin

    Full Text Available Loss of integrity of the basal forebrain cholinergic neurons is a consistent feature of Alzheimer's disease, and measurement of basal forebrain degeneration by magnetic resonance imaging is emerging as a sensitive diagnostic marker for prodromal disease. It is also known that Alzheimer's disease patients perform poorly on both real space and computerized cued (allothetic or uncued (idiothetic recall navigation tasks. Although the hippocampus is required for allothetic navigation, lesions of this region only mildly affect idiothetic navigation. Here we tested the hypothesis that the cholinergic medial septo-hippocampal circuit is important for idiothetic navigation. Basal forebrain cholinergic neurons were selectively lesioned in mice using the toxin saporin conjugated to a basal forebrain cholinergic neuronal marker, the p75 neurotrophin receptor. Control animals were able to learn and remember spatial information when tested on a modified version of the passive place avoidance test where all extramaze cues were removed, and animals had to rely on idiothetic signals. However, the exploratory behaviour of mice with cholinergic basal forebrain lesions was highly disorganized during this test. By contrast, the lesioned animals performed no differently from controls in tasks involving contextual fear conditioning and spatial working memory (Y maze, and displayed no deficits in potentially confounding behaviours such as motor performance, anxiety, or disturbed sleep/wake cycles. These data suggest that the basal forebrain cholinergic system plays a specific role in idiothetic navigation, a modality that is impaired early in Alzheimer's disease.

  13. Fasting stimulates 2-AG biosynthesis in the small intestine: role of cholinergic pathways.

    Science.gov (United States)

    DiPatrizio, Nicholas V; Igarashi, Miki; Narayanaswami, Vidya; Murray, Conor; Gancayco, Joseph; Russell, Amy; Jung, Kwang-Mook; Piomelli, Daniele

    2015-10-15

    The endocannabinoids are lipid-derived signaling molecules that control feeding and energy balance by activating CB1-type cannabinoid receptors in the brain and peripheral tissues. Previous studies have shown that oral exposure to dietary fat stimulates endocannabinoid signaling in the rat small intestine, which provides positive feedback that drives further food intake and preference for fat-rich foods. We now describe an unexpectedly broader role for cholinergic signaling of the vagus nerve in the production of the endocannabinoid, 2-arachidonoyl-sn-glycerol (2-AG), in the small intestine. We show that food deprivation increases levels of 2-AG and its lipid precursor, 1,2-diacylglycerol, in rat jejunum mucosa in a time-dependent manner. This response is abrogated by surgical resection of the vagus nerve or pharmacological blockade of small intestinal subtype-3 muscarinic acetylcholine (m3 mAch) receptors, but not inhibition of subtype-1 muscarinic acetylcholine (m1 mAch). We further show that blockade of peripheral CB1 receptors or intestinal m3 mAch receptors inhibits refeeding in fasted rats. The results suggest that food deprivation stimulates 2-AG-dependent CB1 receptor activation through a mechanism that requires efferent vagal activation of m3 mAch receptors in the jejunum, which, in turn, may promote feeding after a fast. PMID:26290104

  14. Centrifugal compressor design for electrically assisted boost

    Science.gov (United States)

    Y Yang, M.; Martinez-Botas, R. F.; Zhuge, W. L.; Qureshi, U.; Richards, B.

    2013-12-01

    Electrically assisted boost is a prominent method to solve the issues of transient lag in turbocharger and remains an optimized operation condition for a compressor due to decoupling from turbine. Usually a centrifugal compressor for gasoline engine boosting is operated at high rotational speed which is beyond the ability of an electric motor in market. In this paper a centrifugal compressor with rotational speed as 120k RPM and pressure ratio as 2.0 is specially developed for electrically assisted boost. A centrifugal compressor including the impeller, vaneless diffuser and the volute is designed by meanline method followed by 3D detailed design. Then CFD method is employed to predict as well as analyse the performance of the design compressor. The results show that the pressure ratio and efficiency at design point is 2.07 and 78% specifically.

  15. Improved Stereo Matching With Boosting Method

    Directory of Open Access Journals (Sweden)

    Shiny B

    2015-06-01

    Full Text Available Abstract This paper presents an approach based on classification for improving the accuracy of stereo matching methods. We propose this method for occlusion handling. This work employs classification of pixels for finding the erroneous disparity values. Due to the wide applications of disparity map in 3D television medical imaging etc the accuracy of disparity map has high significance. An initial disparity map is obtained using local or global stereo matching methods from the input stereo image pair. The various features for classification are computed from the input stereo image pair and the obtained disparity map. Then the computed feature vector is used for classification of pixels by using GentleBoost as the classification method. The erroneous disparity values in the disparity map found by classification are corrected through a completion stage or filling stage. A performance evaluation of stereo matching using AdaBoostM1 RUSBoost Neural networks and GentleBoost is performed.

  16. Boost Breaking in the EFT of Inflation

    CERN Document Server

    Delacretaz, Luca V; Senatore, Leonardo

    2015-01-01

    If time-translations are spontaneously broken, so are boosts. This symmetry breaking pattern can be non-linearly realized by either just the Goldstone boson of time translations, or by four Goldstone bosons associated with time translations and boosts. In this paper we extend the Effective Field Theory of Multifield Inflation to consider the case in which the additional Goldstone bosons associated with boosts are light and coupled to the Goldstone boson of time translations. The symmetry breaking pattern forces a coupling to curvature so that the mass of the additional Goldstone bosons is predicted to be equal to $\\sqrt{2}H$ in the vast majority of the parameter space where they are light. This pattern therefore offers a natural way of generating self-interacting particles with Hubble mass during inflation. After constructing the general effective Lagrangian, we study how these particles mix and interact with the curvature fluctuations, generating potentially detectable non-Gaussian signals.

  17. Centrifugal compressor design for electrically assisted boost

    International Nuclear Information System (INIS)

    Electrically assisted boost is a prominent method to solve the issues of transient lag in turbocharger and remains an optimized operation condition for a compressor due to decoupling from turbine. Usually a centrifugal compressor for gasoline engine boosting is operated at high rotational speed which is beyond the ability of an electric motor in market. In this paper a centrifugal compressor with rotational speed as 120k RPM and pressure ratio as 2.0 is specially developed for electrically assisted boost. A centrifugal compressor including the impeller, vaneless diffuser and the volute is designed by meanline method followed by 3D detailed design. Then CFD method is employed to predict as well as analyse the performance of the design compressor. The results show that the pressure ratio and efficiency at design point is 2.07 and 78% specifically

  18. New approaches for boosting to uniformity

    International Nuclear Information System (INIS)

    The use of multivariate classifiers has become commonplace in particle physics. To enhance the performance, a series of classifiers is typically trained; this is a technique known as boosting. This paper explores several novel boosting methods that have been designed to produce a uniform selection efficiency in a chosen multivariate space. Such algorithms have a wide range of applications in particle physics, from producing uniform signal selection efficiency across a Dalitz-plot to avoiding the creation of false signal peaks in an invariant mass distribution when searching for new particles

  19. Concomitant boost radiotherapy in oropharynx carcinomas

    OpenAIRE

    Bieri, Sabine; Allal, Abdelkarim Said; Dulguerov, Pavel; Lehmann, Willy; Kurtz, John

    1998-01-01

    Fifty-five patients with resectable and unresectable oropharynx carcinomas were treated with concomitant boost radiotherapy. Forty-two of the patients (76%) had stages III-IV disease. Although none of the patients had undergone major surgery to the primary tumor, 11 had neck dissections prior to radiotherapy, and 19 (35%) received chemotherapy. The planned total tumor dose was 69.9 Gy, delivered over 5.5 weeks. During the last 3.5 weeks, a boost to the initial gross disease was delivered in 1...

  20. Entanglement asymmetry for boosted black branes

    CERN Document Server

    Mishra, Rohit

    2016-01-01

    We study the effects of asymmetry in entanglement thermodynamics of the CFT subsystems. It is found that `boosted' $p$-branes backgrounds give rise to the first law of the entanglement thermodynamics where the CFT pressure plays decisive role in the entanglement. Two different strip like subsystems, one parallel to the boost and the other perpendicular, are studied in the perturbative regime, where $T_{thermal}\\ll T_E$. We also discuss the AdS-wave backgrounds where some universal bounds can be obtained.

  1. Three papers on boosting: an introduction

    OpenAIRE

    Koltchinskii, Vladimir; Yu, Bin

    2004-01-01

    The notion of boosting originated in the Machine Learning literature in the 1980's [VALIANT, L.G. (1984). A theory of the learnable. In Proc. 16th Annual ACM Symposium on Theory of Computing 436-445. ACM Press, New York]. The goal of boosting is to improve the generalization performance of weak (or base) learning algorithms by combining them in a certain way. The first algorithm of this type was discovered by Schapire [SCHAPIRE, R.E. (1990). The strength of weak learnability. Machine Learning...

  2. Boosting BCG-primed responses with a subunit Apa vaccine during the waning phase improves immunity and imparts protection against Mycobacterium tuberculosis.

    Science.gov (United States)

    Nandakumar, Subhadra; Kannanganat, Sunil; Dobos, Karen M; Lucas, Megan; Spencer, John S; Amara, Rama Rao; Plikaytis, Bonnie B; Posey, James E; Sable, Suraj B

    2016-01-01

    Heterologous prime-boosting has emerged as a powerful vaccination approach against tuberculosis. However, optimal timing to boost BCG-immunity using subunit vaccines remains unclear in clinical trials. Here, we followed the adhesin Apa-specific T-cell responses in BCG-primed mice and investigated its BCG-booster potential. The Apa-specific T-cell response peaked 32-52 weeks after parenteral or mucosal BCG-priming but waned significantly by 78 weeks. A subunit-Apa-boost during the contraction-phase of BCG-response had a greater effect on the magnitude and functional quality of specific cellular and humoral responses compared to a boost at the peak of BCG-response. The cellular response increased following mucosal BCG-prime-Apa-subunit-boost strategy compared to Apa-subunit-prime-BCG-boost approach. However, parenteral BCG-prime-Apa-subunit-boost by a homologous route was the most effective strategy in-terms of enhancing specific T-cell responses during waning in the lung and spleen. Two Apa-boosters markedly improved waning BCG-immunity and significantly reduced Mycobacterium tuberculosis burdens post-challenge. Our results highlight the challenges of optimization of prime-boost regimens in mice where BCG drives persistent immune-activation and suggest that boosting with a heterologous vaccine may be ideal once the specific persisting effector responses are contracted. Our results have important implications for design of prime-boost regimens against tuberculosis in humans. PMID:27173443

  3. Age-dependent loss of cholinergic neurons in learning and memory-related brain regions and impaired learning in SAMP8 mice with trigeminal nerve damage.

    Science.gov (United States)

    He, Yifan; Zhu, Jihong; Huang, Fang; Qin, Liu; Fan, Wenguo; He, Hongwen

    2014-11-15

    The tooth belongs to the trigeminal sensory pathway. Dental damage has been associated with impairments in the central nervous system that may be mediated by injury to the trigeminal nerve. In the present study, we investigated the effects of damage to the inferior alveolar nerve, an important peripheral nerve in the trigeminal sensory pathway, on learning and memory behaviors and structural changes in related brain regions, in a mouse model of Alzheimer's disease. Inferior alveolar nerve transection or sham surgery was performed in middle-aged (4-month-old) or elderly (7-month-old) senescence-accelerated mouse prone 8 (SAMP8) mice. When the middle-aged mice reached 8 months (middle-aged group 1) or 11 months (middle-aged group 2), and the elderly group reached 11 months, step-down passive avoidance and Y-maze tests of learning and memory were performed, and the cholinergic system was examined in the hippocampus (Nissl staining and acetylcholinesterase histochemistry) and basal forebrain (choline acetyltransferase immunohistochemistry). In the elderly group, animals that underwent nerve transection had fewer pyramidal neurons in the hippocampal CA1 and CA3 regions, fewer cholinergic fibers in the CA1 and dentate gyrus, and fewer cholinergic neurons in the medial septal nucleus and vertical limb of the diagonal band, compared with sham-operated animals, as well as showing impairments in learning and memory. Conversely, no significant differences in histology or behavior were observed between middle-aged group 1 or group 2 transected mice and age-matched sham-operated mice. The present findings suggest that trigeminal nerve damage in old age, but not middle age, can induce degeneration of the septal-hippocampal cholinergic system and loss of hippocampal pyramidal neurons, and ultimately impair learning ability. Our results highlight the importance of active treatment of trigeminal nerve damage in elderly patients and those with Alzheimer's disease, and indicate that

  4. Hippocampal formation is involved in movement selection: evidence from medial septal cholinergic modulation and concurrent slow-wave (theta rhythm) recording.

    Science.gov (United States)

    Oddie, S D; Kirk, I J; Whishaw, I Q; Bland, B H

    1997-11-01

    Hippocampal rhythmical slow-wave field activity which occurs in response to sensory stimulation is predominantly cholinergic (atropine-sensitive theta rhythm), can precede movement initiation, and co-occurs during non-cholinergic theta rhythm associated with ongoing movement (atropine-resistant). This relationship suggests that theta rhythm plays some role in movement control. The present naturalistic experiments tested the idea that atropine-sensitive theta rhythm plays a role in sensory integration and planning required for initiating appropriate movements. One of a pair of hungry rats, the victim, implanted with hippocampal field recording electrodes, a septal injection cannula, and a posterior hypothalamic stimulating electrode, was given food which the other, the robber, tries to steal. Since the victim dodges from the robber with a latency, distance, and velocity dependent upon the size of the food, elapsed eating time, and proximity of the robber, the movement requires sensory integration and planning. Although eating behavior seemed normal, atropine-sensitive theta rhythm and dodging were disrupted by an infusion of a cholinergic antagonist into the medial septum. When the victim in turn attempted to steal the food back, Type 1 theta rhythm was present and robbery attempts seemed normal. Prior to cholinergic blockade, posterior hypothalamic stimulation produced theta rhythm and dodges, even in the absence of the robber, but following injections, atropine-sensitive theta rhythm and dodging were absent as the animals dropped the food and ran. The results provide the first evidence to link atropine-sensitive theta rhythm and hippocampal structures to a role in sensory integration and planning for the initiation of movement. PMID:9404626

  5. Substitution of natural sensory input by artificial neurostimulation of an amputated trigeminal nerve does not prevent the degeneration of basal forebrain cholinergic circuits projecting to the somatosensory cortex

    Directory of Open Access Journals (Sweden)

    Fivos Panetsos

    2014-11-01

    Full Text Available Peripheral deafferentation downregulates acetylcholine (ACh synthesis in sensory cortices. However the responsible neural circuits and processes are not known. We irreversibly transected the rat infraorbital nerve and implanted neuroprosthetic microdevices for proximal stump stimulation, and assessed cytochrome-oxidase and choline- acetyl-transferase (ChAT in somatosensory, auditory and visual cortices; estimated the number and density of ACh-neurons in the magnocellular basal nucleus (MBN; and localized down-regulated ACh-neurons in basal forebrain using retrograde labeling from deafferented cortices. Here we show that nerve transection, causes down regulation of MBN cholinergic neurons. Stimulation of the cut nerve reverses the metabolic decline but does not affect the decrease in cholinergic fibers in cortex or cholinergic neurons in basal forebrain. Artifical stimulation of the nerve also has no affect of ACh-innervation of other cortices. Cortical ChAT depletion is due to loss of corticopetal MBN ChAT-expressing neurons. MBN ChAT downregulation is not due to decrease neither of afferent activity nor to failure of trophic support. Basalocortical ACh circuits are sensory specific, ACh is provided to each sensory cortex "on demand" by dedicated circuits. Our data support the existence of a modality-specific cortex-MBN-cortex circuit for cognitive information processing.

  6. Cognitive Impairments Induced by Concussive Mild Traumatic Brain Injury in Mouse Are Ameliorated by Treatment with Phenserine via Multiple Non-Cholinergic and Cholinergic Mechanisms

    Science.gov (United States)

    Li, Yazhou; Yu, Qian-sheng; Barak, Shani; Tamargo, Ian A.; Rubovitch, Vardit; Holloway, Harold W.; Lehrmann, Elin; Wood, William H.; Zhang, Yongqing; Becker, Kevin G.; Perez, Evelyn; Van Praag, Henriette; Luo, Yu; Hoffer, Barry J.; Becker, Robert E.; Pick, Chaim G.; Greig, Nigel H.

    2016-01-01

    Traumatic brain injury (TBI), often caused by a concussive impact to the head, affects an estimated 1.7 million Americans annually. With no approved drugs, its pharmacological treatment represents a significant and currently unmet medical need. In our prior development of the anti-cholinesterase compound phenserine for the treatment of neurodegenerative disorders, we recognized that it also possesses non-cholinergic actions with clinical potential. Here, we demonstrate neuroprotective actions of phenserine in neuronal cultures challenged with oxidative stress and glutamate excitotoxicity, two insults of relevance to TBI. These actions translated into amelioration of spatial and visual memory impairments in a mouse model of closed head mild TBI (mTBI) two days following cessation of clinically translatable dosing with phenserine (2.5 and 5.0 mg/kg BID x 5 days initiated post mTBI) in the absence of anti-cholinesterase activity. mTBI elevated levels of thiobarbituric acid reactive substances (TBARS), a marker of oxidative stress. Phenserine counteracted this by augmenting homeostatic mechanisms to mitigate oxidative stress, including superoxide dismutase [SOD] 1 and 2, and glutathione peroxidase [GPx], the activity and protein levels of which were measured by specific assays. Microarray analysis of hippocampal gene expression established that large numbers of genes were exclusively regulated by each individual treatment with a substantial number of them co-regulated between groups. Molecular pathways associated with lipid peroxidation were found to be regulated by mTBI, and treatment of mTBI animals with phenserine effectively reversed injury-induced regulations in the ‘Blalock Alzheimer’s Disease Up’ pathway. Together these data suggest that multiple phenserine-associated actions underpin this compound’s ability to ameliorate cognitive deficits caused by mTBI, and support the further evaluation of the compound as a therapeutic for TBI. PMID:27254111

  7. Bioinspired materials: Boosting plant biology

    Science.gov (United States)

    Scholes, Gregory D.; Sargent, Edward H.

    2014-04-01

    Chloroplasts with extended photosynthetic activity beyond the visible absorption spectrum, and living leaves that perform non-biological functions, are made possible by localizing nanoparticles within plant organelles.

  8. Ligands for SPECT and PET imaging of muscarinic-cholinergic receptors of the heart and brain

    Energy Technology Data Exchange (ETDEWEB)

    Knapp, F.F. Jr.; McPherson, D.W.; Luo, H. [and others

    1995-06-01

    Interest in the potential use of cerebral SPECT and PET imaging for determination of the density and activity of muscarinic-cholinergic receptors (mAChR) has been stimulated by the changes in these receptors which occur in many neurological diseases. In addition, the important involvement of mAChR in modulating negative inotropic cardiac activity suggests that such receptor ligands may have important applications in evaluation of changes which may occur in cardiac disease. In this paper, the properties of several key muscarinic receptor ligands being developed or which have been used for clinical SPECT and PET are discussed. In addition, the ORNL development of the new iodinated IQNP ligand based on QNB and the results of in vivo biodistribution studies in rats, in vitro competitive binding studies and ex vivo autoradiographic experiments are described. The use of radioiodinated IQNP may offer several advantages in comparison to IQNB because of its easy and high yield preparation and high brain uptake and the potential usefulness of the {open_quotes}partial{close_quotes} subtype selective IONP isomers. We also describe the development of new IQNP-type analogues which offer the opportunity for radiolabeling with positron-emitting radioisotopes (carbon-11, fluorine-18 and bromine-76) for potential use with PET.

  9. Noradrenergic and cholinergic modulation of late ERP responses to deviant stimuli.

    Science.gov (United States)

    Brown, Stephen B R E; van der Wee, Nic J A; van Noorden, Martijn S; Giltay, Erik J; Nieuwenhuis, Sander

    2015-12-01

    Researchers have proposed several hypotheses about the neuromodulator systems involved in generating P3 components of the ERP. To test some of these hypotheses, we conducted a randomized placebo-controlled crossover study in which we investigated how the late positive ERP response to deviant stimuli is modulated by (a) clonidine, an α2 agonist that attenuates baseline noradrenergic activity; and (b) scopolamine, a muscarinic antagonist of acetylcholine receptors. We collected EEG data from 18 healthy volunteers during the performance of an auditory oddball task with several active and passive task conditions. We then used temporospatial principal component analysis (PCA) to decompose the ERP waveforms. The PCA revealed two distinct late positive ERP components: the classic parietal P300 and the frontal novelty P3. Statistical analysis of the temporospatial factor scores indicated that in most conditions the amplitude of the classic P300 was increased by clonidine and scopolamine. In contrast, the amplitude of the novelty P3 was decreased by both drugs. The similar pattern of results for clonidine and scopolamine probably reflects the strong interactions between the noradrenergic and cholinergic systems. The results, in combination with previous pharmacological studies, suggest a critical role for both neuromodulator systems in the generation of the P300 and the novelty P3. PMID:26352794

  10. Music Might Give Babies' Language Skills a Boost

    Science.gov (United States)

    ... nlm.nih.gov/medlineplus/news/fullstory_158486.html Music Might Give Babies' Language Skills a Boost Small ... April 25, 2016 (HealthDay News) -- Can listening to music boost your baby's brainpower? Maybe, at least in ...

  11. Music Might Give Babies' Language Skills a Boost

    Science.gov (United States)

    ... page: https://medlineplus.gov/news/fullstory_158486.html Music Might Give Babies' Language Skills a Boost Small ... April 25, 2016 (HealthDay News) -- Can listening to music boost your baby's brainpower? Maybe, at least in ...

  12. Boosted Neural Networks in Evolutionary Computation

    Czech Academy of Sciences Publication Activity Database

    Holeňa, Martin; Linke, D.; Steinfeldt, N.

    Bangkok : King Mongkut's University of Technology Thonburi, 2009. s. 225-226. [ICONIP 2009. International Conference on Neural Information Processing /16./. 01.12.2009-05.12.2009, Bangkok] Institutional research plan: CEZ:AV0Z10300504 Keywords : evolutionary algorithms * empirical objective functions * surrogate modelling * surrogate modelling * artificial neural networks * boosting Subject RIV: IN - Informatics, Computer Science

  13. Taxation Policies Adjust,Motor Vehicles Boost

    Institute of Scientific and Technical Information of China (English)

    Alice

    2007-01-01

    @@ In recent years,Chinese automotive industry,as one of the pillar industries has kept on rising.In 2006,Chinese auto production ranked the third in the world.The governmental authorities are also studying the corresponding taxations to boost the healthy development of Chinese automotive industry.

  14. The Attentional Boost Effect and Context Memory

    Science.gov (United States)

    Mulligan, Neil W.; Smith, S. Adam; Spataro, Pietro

    2016-01-01

    Stimuli co-occurring with targets in a detection task are better remembered than stimuli co-occurring with distractors--the attentional boost effect (ABE). The ABE is of interest because it is an exception to the usual finding that divided attention during encoding impairs memory. The effect has been demonstrated in tests of item memory but it is…

  15. Pharmacological Mechanisms of Cortical Enhancement Induced by the Repetitive Pairing of Visual/Cholinergic Stimulation.

    Directory of Open Access Journals (Sweden)

    Jun-Il Kang

    Full Text Available Repetitive visual training paired with electrical activation of cholinergic projections to the primary visual cortex (V1 induces long-term enhancement of cortical processing in response to the visual training stimulus. To better determine the receptor subtypes mediating this effect the selective pharmacological blockade of V1 nicotinic (nAChR, M1 and M2 muscarinic (mAChR or GABAergic A (GABAAR receptors was performed during the training session and visual evoked potentials (VEPs were recorded before and after training. The training session consisted of the exposure of awake, adult rats to an orientation-specific 0.12 CPD grating paired with an electrical stimulation of the basal forebrain for a duration of 1 week for 10 minutes per day. Pharmacological agents were infused intracortically during this period. The post-training VEP amplitude was significantly increased compared to the pre-training values for the trained spatial frequency and to adjacent spatial frequencies up to 0.3 CPD, suggesting a long-term increase of V1 sensitivity. This increase was totally blocked by the nAChR antagonist as well as by an M2 mAChR subtype and GABAAR antagonist. Moreover, administration of the M2 mAChR antagonist also significantly decreased the amplitude of the control VEPs, suggesting a suppressive effect on cortical responsiveness. However, the M1 mAChR antagonist blocked the increase of the VEP amplitude only for the high spatial frequency (0.3 CPD, suggesting that M1 role was limited to the spread of the enhancement effect to a higher spatial frequency. More generally, all the drugs used did block the VEP increase at 0.3 CPD. Further, use of each of the aforementioned receptor antagonists blocked training-induced changes in gamma and beta band oscillations. These findings demonstrate that visual training coupled with cholinergic stimulation improved perceptual sensitivity by enhancing cortical responsiveness in V1. This enhancement is mainly mediated by n

  16. A Boosting Framework on Grounds of Online Learning

    OpenAIRE

    Naghibi, Tofigh; Pfister, Beat

    2014-01-01

    By exploiting the duality between boosting and online learning, we present a boosting framework which proves to be extremely powerful thanks to employing the vast knowledge available in the online learning area. Using this framework, we develop various algorithms to address multiple practically and theoretically interesting questions including sparse boosting, smooth-distribution boosting, agnostic learning and some generalization to double-projection online learning algorithms, as a by-product.

  17. Formation and Dynamics of Waves in a Cortical Model of Cholinergic Modulation.

    Directory of Open Access Journals (Sweden)

    James P Roach

    2015-08-01

    Full Text Available Acetylcholine (ACh is a regulator of neural excitability and one of the neurochemical substrates of sleep. Amongst the cellular effects induced by cholinergic modulation are a reduction in spike-frequency adaptation (SFA and a shift in the phase response curve (PRC. We demonstrate in a biophysical model how changes in neural excitability and network structure interact to create three distinct functional regimes: localized asynchronous, traveling asynchronous, and traveling synchronous. Our results qualitatively match those observed experimentally. Cortical activity during slow wave sleep (SWS differs from that during REM sleep or waking states. During SWS there are traveling patterns of activity in the cortex; in other states stationary patterns occur. Our model is a network composed of Hodgkin-Huxley type neurons with a M-current regulated by ACh. Regulation of ACh level can account for dynamical changes between functional regimes. Reduction of the magnitude of this current recreates the reduction in SFA the shift from a type 2 to a type 1 PRC observed in the presence of ACh. When SFA is minimal (in waking or REM sleep state, high ACh patterns of activity are localized and easily pinned by network inhomogeneities. When SFA is present (decreasing ACh, traveling waves of activity naturally arise. A further decrease in ACh leads to a high degree of synchrony within traveling waves. We also show that the level of ACh determines how sensitive network activity is to synaptic heterogeneity. These regimes may have a profound functional significance as stationary patterns may play a role in the proper encoding of external input as memory and traveling waves could lead to synaptic regularization, giving unique insights into the role and significance of ACh in determining patterns of cortical activity and functional differences arising from the patterns.

  18. Alpha-asarone improves striatal cholinergic function and locomotor hyperactivity in Fmr1 knockout mice.

    Science.gov (United States)

    Qiu, Guozhen; Chen, Shengqiang; Guo, Jialing; Wu, Jie; Yi, Yong-Hong

    2016-10-01

    Hyperactivity is a symptom found in several neurological and psychiatric disorders, including Fragile X syndrome (FXS). The animal model of FXS, fragile X mental retardation gene (Fmr1) knockout (KO) mouse, exhibits robust locomotor hyperactivity. Alpha (α)-asarone, a major bioactive component isolated from Acorus gramineus, has been shown in previous studies to improve various disease conditions including central nervous system disorders. In this study, we show that treatment with α-asarone alleviates locomotor hyperactivity in Fmr1 KO mice. To elucidate the mechanism underlying this improvement, we evaluated the expressions of various cholinergic markers, as well as acetylcholinesterase (AChE) activity and acetylcholine (ACh) levels, in the striatum of Fmr1 KO mice. We also analyzed the AChE-inhibitory activity of α-asarone. Striatal samples from Fmr1 KO mice showed decreased m1 muscarinic acetylcholine receptor (m1 mAChR) expression, increased AChE activity, and reduced ACh levels. Treatment with α-asarone improved m1 mAChR expression and ACh levels, and attenuated the increased AChE activity. In addition, α-asarone dose-dependently inhibited AChE activity in vitro. These results indicate that direct inhibition of AChE activity and up-regulation of m1 mAChR expression in the striatum might contribute to the beneficial effects of α-asarone on locomotor hyperactivity in Fmr1 KO mice. These findings might improve understanding of the neurobiological mechanisms responsible for locomotor hyperactivity. PMID:27316341

  19. Dynamic Analysis of a Boost Topology with Ripple Cancellation and Comparison with the Conventional Boost

    OpenAIRE

    Díaz López, Daniel; Meneses Herrera, David; Oliver Ramírez, Jesús Angel; García Suárez, Oscar; Alou Cervera, Pedro; Cobos Márquez, José Antonio

    2009-01-01

    The boost topology with ripple cancellation network allows input and output current ripple attenuation, which means the suppression of the input filter and a high reduction of the output filter. However, to achieve the ripple cancellation, the complexity and the number of components of the converter increase compared with the conventional boost. A detailed analysis has been developed to specify the advantages and drawbacks of this topology. This paper presents the averaged model that derives ...

  20. Primary Paralleled Isolated Boost Converter with Extended Operating Voltage Range

    DEFF Research Database (Denmark)

    Hernandez Botella, Juan Carlos; Sen, Gökhan; Mira Albert, Maria del Carmen;

    2012-01-01

    Applications requiring wide input and output voltage range cannot often be satisfied by using buck or boost derived topologies. Primary paralleled isolated boost converter (PPIBC) [1]-[2] is a high efficiency boost derived topology. This paper proposes a new operation mode for extending the input...

  1. The Role of Gut Microflora and the Cholinergic Anti-inflammatory Neuroendocrine System in Diabetes Mellitus

    Science.gov (United States)

    Parekh, Parth J.; Nayi, Vipul R.; Johnson, David A.; Vinik, Aaron I.

    2016-01-01

    The obesity epidemic has drastically impacted the state of health care in the United States. Paralleling this epidemic is the incidence of diabetes mellitus, with a notable shift toward a much younger age of onset. While central to the pathogenesis of diabetes associated with obesity is the role of inflammation attributed to “adiposopathy.” Emerging data suggest that changes in sympathetic/parasympathetic balance regulated by the brain precede changes in the inflammatory cascade. It has now been established that the gut microflora contributes significantly to the activation and inhibition of autonomic control and impact the set of the neuroinflammatory inhibitory reflex mediated by the cholinergic nervous system. There has been a paradigm shift toward further investigating commensal bacteria in the pathogenesis of obesity and diabetes mellitus and its complications, as dysbiosis is thought to play a pivotal role in diabetic-associated disorders. This paper is intended to evaluate the role of intestinal dysbiosis in the pathogenesis of diabetes mellitus and examine the potential for restoration of balance via use of probiotics. PMID:27375553

  2. Behavioral deficits and cholinergic pathway abnormalities in male Sanfilippo B mice.

    Science.gov (United States)

    Kan, Shih-Hsin; Le, Steven Q; Bui, Quang D; Benedict, Braeden; Cushman, Jesse; Sands, Mark S; Dickson, Patricia I

    2016-10-01

    Sanfilippo B syndrome is a progressive neurological disorder caused by inability to catabolize heparan sulfate glycosaminoglycans. We studied neurobehavior in male Sanfilippo B mice and heterozygous littermate controls from 16 to 20 weeks of age. Affected mice showed reduced anxiety, with a decrease in the number of stretch-attend postures during the elevated plus maze (p=0.001) and an increased tendency to linger in the center of an open field (p=0.032). Water maze testing showed impaired spatial learning, with reduced preference for the target quadrant (p=0.01). In radial arm maze testing, affected mice failed to achieve above-chance performance in a win-shift working memory task (t-test relative to 50% chance: p=0.289), relative to controls (p=0.037). We found a 12.4% reduction in mean acetylcholinesterase activity (padult-onset dementias, including Alzheimer disease. Our results suggest that male Sanfilippo B mice display neurobehavioral deficits at a relatively early age, and that as in adult dementias, they may display deficits in cholinergic pathways. PMID:27340089

  3. The Role of Gut Microflora and the Cholinergic Anti-inflammatory Neuroendocrine System in Diabetes Mellitus.

    Science.gov (United States)

    Parekh, Parth J; Nayi, Vipul R; Johnson, David A; Vinik, Aaron I

    2016-01-01

    The obesity epidemic has drastically impacted the state of health care in the United States. Paralleling this epidemic is the incidence of diabetes mellitus, with a notable shift toward a much younger age of onset. While central to the pathogenesis of diabetes associated with obesity is the role of inflammation attributed to "adiposopathy." Emerging data suggest that changes in sympathetic/parasympathetic balance regulated by the brain precede changes in the inflammatory cascade. It has now been established that the gut microflora contributes significantly to the activation and inhibition of autonomic control and impact the set of the neuroinflammatory inhibitory reflex mediated by the cholinergic nervous system. There has been a paradigm shift toward further investigating commensal bacteria in the pathogenesis of obesity and diabetes mellitus and its complications, as dysbiosis is thought to play a pivotal role in diabetic-associated disorders. This paper is intended to evaluate the role of intestinal dysbiosis in the pathogenesis of diabetes mellitus and examine the potential for restoration of balance via use of probiotics. PMID:27375553

  4. Chronic Cerebral Ischaemia Forms New Cholinergic Mechanisms of Learning and Memory

    Directory of Open Access Journals (Sweden)

    E. I. Zakharova

    2010-01-01

    Full Text Available The purpose of this research was a comparative analysis of cholinergic synaptic organization following learning and memory in normal and chronic cerebral ischaemic rats in the Morris water maze model. Choline acetyltransferase and protein content were determined in subpopulations of presynapses of “light” and “heavy” synaptosomal fractions of the cortex and the hippocampus, and the cholinergic projective and intrinsic systems of the brain structures were taken into consideration. We found a strong involvement of cholinergic systems, both projective and intrinsic, in all forms of cognition. Each form of cognition had an individual cholinergic molecular profile and the cholinergic synaptic compositions in the ischaemic rat brains differed significantly from normal ones. Our data demonstrated that under ischaemic conditions, instead of damaged connections new key synaptic relationships, which were stable against pathological influences and able to restore damaged cognitive functions, arose. The plasticity of neurochemical links in the individual organization of certain types of cognition gave a new input into brain pathology and can be used in the future for alternative corrections of vascular and other degenerative dementias.

  5. TITERS OF ANTIBODIES TO Β1-ADRENOCEPTOR AND M2 CHOLINERGIC RECEPTORS IN PATIENTS WITH VENTRICULAR ARRHYTHMIAS WITHOUT AN ORGANIC CARDIOVASCULAR DISEASE AND THEIR POSSIBLE CLINICAL SIGNIFICANCE

    Directory of Open Access Journals (Sweden)

    M. M. Rogova

    2015-12-01

    Full Text Available Aim. To identify the most promising epitopes that simulate various sites β1-adrenergic and M2-cholinergic receptors, and to evaluate their possible contribution to the development and maintenance of cardiac arrhythmias, particularly idiopathic ventricular arrhythmia. Material and methods. Patients with ventricular arrhythmias without organic cardiovascular disease (the study group; n=70 were included in the study. The control group consisted of 20 healthy volunteers. Evaluation of levels of antibodies to antigenic determinants, modeling various sites β1-adrenergic and M2-cholinergic performed in all patients. Causal treatment with clarithromycin and valacyclovir performed in part of patients. Results. Antibodies to different peptide sequences of β1-adrenergic and M2-cholinergic receptors have been identified in 25% of main group patients. A direct correlation between the frequency of episodes of ventricular tachycardia and IgG levels to MRI-MRIV (p=0.02 revealed. Increase in titre of antibodies to β1-adrenoceptors, to a peptide sequence β8 (p=0.02, and lower titers of antibodies to the M2 acetylcholine receptor — chimera MRI-MRIV IgM (p=0.06 and ARI-MRIV IgM (p=0.07 were observed when assessing the efficacy of the therapy in the causal dynamics in the group of "untreated" patients. IgG titer reduction of ARI-MRIV (p=0.02, which is 4 times out of 10 with reduction of ventricular ectopic activity , recorded after valacyclovir therapy. Clarithromycin therapy on the level of antibodies exerted no significant effect. Conclusion. Possible involvement of antibodies to β1-adrenoceptor and M2-cholinergic receptors in the development of idiopathic ventricular arrhythmias demonstrated. The relationship between the frequency of episodes of ventricular tachycardia and levels of antibody titers to M2-cholinergic receptors found. Attempt of causal treatment, depending on the possible mechanisms of the autoimmune process is executed. Further studies to

  6. Boosted Fast Flux Loop Final Report

    International Nuclear Information System (INIS)

    The Boosted Fast Flux Loop (BFFL) project was initiated to determine basic feasibility of designing, constructing, and installing in a host irradiation facility, an experimental vehicle that can replicate with reasonable fidelity the fast-flux test environment needed for fuels and materials irradiation testing for advanced reactor concepts. Originally called the Gas Test Loop (GTL) project, the activity included (1) determination of requirements that must be met for the GTL to be responsive to potential users, (2) a survey of nuclear facilities that may successfully host the GTL, (3) conceptualizing designs for hardware that can support the needed environments for neutron flux intensity and energy spectrum, atmosphere, flow, etc. needed by the experimenters, and (4) examining other aspects of such a system, such as waste generation and disposal, environmental concerns, needs for additional infrastructure, and requirements for interfacing with the host facility. A revised project plan included requesting an interim decision, termed CD-1A, that had objectives of establishing the site for the project at the Advanced Test Reactor (ATR) at the Idaho National Laboratory (INL), deferring the CD 1 application, and authorizing a research program that would resolve the most pressing technical questions regarding GTL feasibility, including issues relating to the use of booster fuel in the ATR. Major research tasks were (1) hydraulic testing to establish flow conditions through the booster fuel, (2) mini-plate irradiation tests and post-irradiation examination to alleviate concerns over corrosion at the high heat fluxes planned, (3) development and demonstration of booster fuel fabrication techniques, and (4) a review of the impact of the GTL on the ATR safety basis. A revised cooling concept for the apparatus was conceptualized, which resulted in renaming the project to the BFFL. Before the subsequent CD-1 approval request could be made, a decision was made in April 2006 that

  7. Cholinergic Neurons - Keeping Check on Amyloid beta in the Cerebral Cortex

    Directory of Open Access Journals (Sweden)

    Saak V. Ovsepian

    2013-12-01

    Full Text Available The physiological relevance of the uptake of ligands with no apparent trophic functions via the p75 neurotrophin receptor (p75NTR remains unclear. Herein, we propose a homeostatic role for this in clearance of amyloid β (Aβ in the brain. We hypothesize that uptake of Aβ in conjunction with p75NTR followed by its degradation in lysosomes endows cholinergic basalo-cortical projections enriched in this receptor a facility for maintaining physiological levels of Aβ in target areas. Thus, in addition to the diffuse modulator influence and channeling of extra-thalamic signals, cholinergic innervations could supply the cerebral cortex with an elaborate system for Aβ drainage. Interpreting the emerging relationship of new molecular data with established role of cholinergic modulator system in regulating cortical network dynamics should provide new insights into the brain physiology and mechanisms of neuro-degenerative diseases.

  8. Cholinergic neuromuscular junctions in Brachionus calyciflorus and Lecane quadridentata (Rotifera:Monogononta)

    Institute of Scientific and Technical Information of China (English)

    Ignacio Alejandro Prez-Legaspi; Alma Lilin Guerrero-Barrera; Ivn Jos Galvn-Mendoza; Jos Luis Quintanar; Roberto Rico-Martnez

    2014-01-01

    Objective:To identify the presence of joint muscular and cholinergic systems in two freshwater rotifer species, Brachionus calyciflorus and Lecane quadridentata. Methods: The muscle actin fibers were stained with phalloidin-linked fluorescent dye, and acetylcholine was detected with Amplex Red Acetylcholine/Acetylcholinesterase Assay Kit, and then confocal scanning laser microscopy was used. Results:The musculature of Brachionus calyciflorus showed a pattern similar to other species of the same genus, while that of Lecane quadridentata was different from other rotifer genera described previously. The cholinergic system was determined by co-localization of both muscles and acetylcholine labels in the whole rotifer, suggesting the presence of neuromuscular junctions. Conclusions: The distribution pattern of muscular and acetylcholine systems showed considerable differences between the two species that might be related to different adaptations to particular ecological niches. The confirmation of a cholinergic system in rotifers contributes to the development of potential neuro-pharmacological and toxicological studies using rotifers as model organism.

  9. Does ICT boost Dutch productivity growth?

    OpenAIRE

    Henry van der Wiel

    2001-01-01

    From an historical and international perspective, Dutch labour productivity growth rates have been lacklustre. Using a growth accounting framework, this document analyses whether ICT has recently boosted Dutch labour productivity growth, similar to developments in the US. Labour productivity growth in the Dutch market sector slightly accelerated in the second half of the 1990s. The acceleration seems to be related to the production and use of ICT. The productivity performance of the Dutch ICT...

  10. Multiclass Boosting for Fast Multiclass Object Detection /

    OpenAIRE

    Saberian, Mohammad

    2014-01-01

    In this thesis the problem of designing a fast multiclass object detector based on cascade architecture is considered. A classifier cascade is a sequence of simple to complex sub-classifiers where each stage either rejects the input or pass it to the next stage. Since most of the non-target inputs get rejected with the simple sub- classifiers in the early stages of the cascade, the overall classification will be fast. Since cascade sub- classifier are usually trained with Boosting algorithms,...

  11. Search for New Physics in Boosted Topologies

    CERN Document Server

    Cochran, James; The ATLAS collaboration

    2014-01-01

    The presentation is expected to focus on the opportunities of discovery of new physics profiting of the latest reconstruction tools for boosted top-quark or boson (W,Z,H) reconstruction and their large effect on increasing the analysis efficiency. A summary of Run 1 results showing latest techniques for background suppression and data-driven background estimate should be included pointing out the possibilities and improvements for Run 2.

  12. Cash boost to Great British science unveiled

    CERN Multimedia

    2002-01-01

    "Trade and Industry Secretary, Patricia Hewitt today unveiled new plans for the DTI's record science budget over the next three years, to keep Britain at the forefront of world science. The plans include funding to develop life saving new health techniques, to seek alternative energy sources, to help our rural economy, to develop the computers of tomorrow and boost business with the next generation of leading edge technologies" (1 page).

  13. Blazar sequence - an artefact of Doppler boosting

    OpenAIRE

    Nieppola, E.; Valtaoja, E.; Tornikoski, M.; Hovatta, T.; Kotiranta, M.

    2008-01-01

    The blazar sequence is a scenario in which the bolometric luminosity of the blazar governs the appearance of its spectral energy distribution. The most prominent result is the significant negative correlation between the synchrotron peak frequencies and the synchrotron peak luminosities of the blazar population. Observational studies of the blazar sequence have, in general, neglected the effect of Doppler boosting. We study the dependence of both the synchrotron peak frequency and luminosity ...

  14. Participation of the cholinergic system in the ethanol-induced suppression of paradoxical sleep in rats

    Directory of Open Access Journals (Sweden)

    L.A. Papale

    2008-09-01

    Full Text Available Sleep disturbance is among the many consequences of ethanol abuse in both humans and rodents. Ethanol consumption can reduce REM or paradoxical sleep (PS in humans and rats, respectively. The first aim of this study was to develop an animal model of ethanol-induced PS suppression. This model administered intragastrically (by gavage to male Wistar rats (3 months old, 200-250 g 0.5 to 3.5 g/kg ethanol. The 3.5 g/kg dose of ethanol suppressed the PS stage compared with the vehicle group (distilled water during the first 2-h interval (0-2 h; 1.3 vs 10.2; P < 0.001. The second aim of this study was to investigate the mechanisms by which ethanol suppresses PS. We examined the effects of cholinergic drug pretreatment. The cholinergic system was chosen because of the involvement of cholinergic neurotransmitters in regulating the sleep-wake cycle. A second set of animals was pretreated with 2.5, 5.0, and 10 mg/kg pilocarpine (cholinergic agonist or atropine (cholinergic antagonist. These drugs were administered 1 h prior to ethanol (3.5 g/kg or vehicle. Treatment with atropine prior to vehicle or ethanol produced a statistically significant decrease in PS, whereas pilocarpine had no effect on minutes of PS. Although the mechanism by which ethanol induces PS suppression is not fully understood, these data suggest that the cholinergic system is not the only system involved in this interaction.

  15. Sexually dimorphic effects of the Lhx7 null mutation on forebrain cholinergic function.

    Science.gov (United States)

    Fragkouli, A; Stamatakis, A; Zographos, E; Pachnis, V; Stylianopoulou, F

    2006-01-01

    It has been reported recently that mice lacking both alleles of the LIM-homeobox gene Lhx7, display dramatically reduced number of forebrain cholinergic neurons. In the present study, we investigated whether the Lhx7 mutation affects male and female mice differently, given the fact that gender differences are consistently observed in forebrain cholinergic function. Our results show that in adult male as well as female Lhx7 homozygous mutants there is a dramatic loss of choline acetyltransferase immunoreactive forebrain neurons, both projection and interneurons. The reduction of forebrain choline acetyltransferase immunoreactive neurons in Lhx7 homozygous mutants is accompanied by a decrease of acetylcholinesterase histochemical staining in all forebrain cholinergic neuron target areas of both male and female homozygous mutants. Furthermore, there was an increase of M1-, but not M2-, muscarinic acetylcholine receptor binding site density in the somatosensory cortex and basal ganglia of only the female homozygous mutant mice. Such an increase can be regarded as a mechanism acting to compensate for the dramatically reduced cholinergic input, raising the possibility that the forebrain cholinergic system in female mice may be more plastic and responsive to situations of limited neurotransmitter availability. Finally, our study provides additional data for the sexual dimorphism of the forebrain cholinergic system, as female mice appear to have a lower density of M1-muscarinic acetylcholine receptors in the striatal areas of the basal ganglia and a higher density of M2-muscarinic acetylcholine receptors, in a number of cortical areas, as well as the striatal areas of the basal ganglia. PMID:16338089

  16. Muscarinic signaling influences the patterning and phenotype of cholinergic amacrine cells in the developing chick retina

    Directory of Open Access Journals (Sweden)

    Fischer Andy J

    2008-02-01

    Full Text Available Abstract Background Many studies in the vertebrate retina have characterized the differentiation of amacrine cells as a homogenous class of neurons, but little is known about the genes and factors that regulate the development of distinct types of amacrine cells. Accordingly, the purpose of this study was to characterize the development of the cholinergic amacrine cells and identify factors that influence their development. Cholinergic amacrine cells in the embryonic chick retina were identified by using antibodies to choline acetyltransferase (ChAT. Results We found that as ChAT-immunoreactive cells differentiate they expressed the homeodomain transcription factors Pax6 and Islet1, and the cell-cycle inhibitor p27kip1. As differentiation proceeds, type-II cholinergic cells, displaced to the ganglion cell layer, transiently expressed high levels of cellular retinoic acid binding protein (CRABP and neurofilament, while type-I cells in the inner nuclear layer did not. Although there is a 1:1 ratio of type-I to type-II cells in vivo, in dissociated cell cultures the type-I cells (ChAT-positive and CRABP-negative out-numbered the type-II cells (ChAT and CRABP-positive cells by 2:1. The relative abundance of type-I to type-II cells was not influenced by Sonic Hedgehog (Shh, but was affected by compounds that act at muscarinic acetylcholine receptors. In addition, the abundance and mosaic patterning of type-II cholinergic amacrine cells is disrupted by interfering with muscarinic signaling. Conclusion We conclude that: (1 during development type-I and type-II cholinergic amacrine cells are not homotypic, (2 the phenotypic differences between these subtypes of cells is controlled by the local microenvironment, and (3 appropriate levels of muscarinic signaling between the cholinergic amacrine cells are required for proper mosaic patterning.

  17. Image enhancement based on edge boosting algorithm

    Science.gov (United States)

    Ngernplubpla, Jaturon; Chitsobhuk, Orachat

    2015-12-01

    In this paper, a technique for image enhancement based on proposed edge boosting algorithm to reconstruct high quality image from a single low resolution image is described. The difficulty in single-image super-resolution is that the generic image priors resided in the low resolution input image may not be sufficient to generate the effective solutions. In order to achieve a success in super-resolution reconstruction, efficient prior knowledge should be estimated. The statistics of gradient priors in terms of priority map based on separable gradient estimation, maximum likelihood edge estimation, and local variance are introduced. The proposed edge boosting algorithm takes advantages of these gradient statistics to select the appropriate enhancement weights. The larger weights are applied to the higher frequency details while the low frequency details are smoothed. From the experimental results, the significant performance improvement quantitatively and perceptually is illustrated. It can be seen that the proposed edge boosting algorithm demonstrates high quality results with fewer artifacts, sharper edges, superior texture areas, and finer detail with low noise.

  18. Investigation into the role of the cholinergic system in radiation-induced damage in the rat liver and ileum

    International Nuclear Information System (INIS)

    It has been previously shown that acetylcholine (ACh) may affect pro-inflammatory and anti-inflammatory cytokines. The role of the cholinergic system in radiation-induced inflammatory responses and tissue damage remains unclear. Therefore, the present study was designed to determine the radio-protective properties of the cholinergic system in the ileum and the liver of rats. Rats were exposed to 8-Gy single-fraction whole-abdominal irradiation and were then decapitated at either 36 h or 10 d post-irradiation. The rats were treated either with intraperitoneal physiological saline (1 ml/kg), physostigmine (80 μg/kg) or atropine (50 μg/kg) twice daily for 36 h or 10 d. Cardiac blood samples and liver and ileal tissues were obtained in which TNF-α, IL-1β and IL-10 levels were assayed using ELISA. In the liver and ileal homogenates, caspase-3 immunoblots were performed and mye-loperoxidase (MPO) activity was analyzed. Plasma levels of IL-1β and TNF-α increased significantly following radiation (P < 0.01 and P < 0.001, respectively) as compared with non-irradiated controls, and physostigmine treatment prevented the increase in the pro-inflammatory cytokines (P < 0.01 and P < 0.001, respectively). Plasma IL-10 levels were not found to be significantly changed following radiation, whereas physostigmine augmented IL-10 levels during the late phase (P < 0.01). In the liver and ileum homogenates, IL-1β and TNF-α levels were also elevated following radiation, and this effect was inhibited by physostigmine treatment but not by atropine. Similarly, physostigmine also reversed the changes in MPO activity and in the caspase-3 levels in the liver and ileum. Histological examination revealed related changes. Physostigmine experiments suggested that ACh has a radio-protective effect not involving the muscarinic receptors. (author)

  19. Effects of mercuric chloride and methyl mercury on cholinergic neuromuscular transmission in the guinea-pig ileum

    International Nuclear Information System (INIS)

    The effects of mercuric chloride (HgCl2) and methyl mercury (MeHg) were examined on basal mechanical activity and electrically-induced neurogenic cholinergic contractions (twitch contractions) in longitudinal muscle-myenteric plexus strips from guinea-pig distal ileum. Both compounds at 0.3-3 μM slightly enhanced the amplitude of twitch contractions in ∼50% preparations. This effect was probably due to facilitation of acetylcholine (ACh) release since 0.1 and 1 μM mercurials increased electrically-evoked tritium outflow from [3H]choline preloaded muscle layer with attached myenteric plexus. Conversely, higher mercury concentrations inhibited twitch contractions (HgCl2 IC50 = 21.3±6.4 μM; MeHg IC50 = 45.1±5.5 μM), as well as contractions to exogenous ACh (0.1 μM) in resting preparations, and concomitantly increased the basal tone. The former effects possibly reflected an anti muscarinic activity of mercury, while the latter was related to alterations of calcium homeostasis in the effector cells. Indeed, the effect of HgCl2 on basal tone was antagonized by the Ca2+ entry blocker nifedipine (3, 10, 30 nM), indicating Hg-induced facilitation of Ca2+ influx through voltage-dependent channels. On the whole, our results suggest that cholinergic neuromuscular transmission and Ca2+-dependent mechanisms underlying smooth muscle contractility are targets for mercury toxicity in the intestine. (au) 51 refs

  20. A cholinergic contribution to the circulatory responses evoked at the onset of handgrip exercise in humans

    DEFF Research Database (Denmark)

    Vianna, Lauro C; Fadel, Paul J; Secher, Niels H; Fisher, James P

    2015-01-01

    A cholinergic (muscarinic) contribution to the initial circulatory response to exercise in humans remains controversial. Herein, we posit that this may be due to exercise mode with a cholinergic contribution being important during isometric handgrip exercise, where the hyperemic response of the...... muscle is relatively small compared with the onset of leg cycling, where a marked increase in muscle blood flow rapidly occurs as a consequence of multiple redundant mechanisms. We recorded blood pressure (BP; brachial artery), stroke volume (pulse contour analysis), cardiac output, and systemic vascular...

  1. Pulse width modulated buck-boost five-level current source inverters

    DEFF Research Database (Denmark)

    Blaabjerg, Frede; Gao, F.; Loh, P.C.;

    2008-01-01

    This paper presents new five-level current source inverters (CSIs) with voltage/current buck-boost capability. Being different from the existing multilevel CSI, the proposed CSIs were first designed to regulate the flowing path of dc input current by controlling two additional active switches, re...

  2. Robust LogitBoost and Adaptive Base Class (ABC) LogitBoost

    CERN Document Server

    Li, Ping

    2012-01-01

    Logitboost is an influential boosting algorithm for classification. In this paper, we develop robust logitboost to provide an explicit formulation of tree-split criterion for building weak learners (regression trees) for logitboost. This formulation leads to a numerically stable implementation of logitboost. We then propose abc-logitboost for multi-class classification, by combining robust logitboost with the prior work of abc-boost. Previously, abc-boost was implemented as abc-mart using the mart algorithm. Our extensive experiments on multi-class classification compare four algorithms: mart, abcmart, (robust) logitboost, and abc-logitboost, and demonstrate the superiority of abc-logitboost. Comparisons with other learning methods including SVM and deep learning are also available through prior publications.

  3. Evidence for broad versus segregated projections from cholinergic and noradrenergic nuclei to functionally and anatomically discrete subregions of prefrontal cortex

    Directory of Open Access Journals (Sweden)

    Daniel J. Chandler

    2012-05-01

    Full Text Available The prefrontal cortex (PFC is implicated in a variety of cognitive and executive operations. However, this region is not a single functional unit; rather, it is composed of several functionally and anatomically distinct networks, including anterior cingulate cortex (ACC, medial prefrontal cortex (mPFC and orbitofrontal cortex (OFC. These prefrontal subregions serve dissociable behavioral functions, and are unique in their afferent and efferent connections. Each of these subregions is innervated by ascending cholinergic and noradrenergic systems, each of which likewise has a distinct role in cognitive function; yet the distribution and projection patterns of cells in the source nuclei for these pathways have not been examined in great detail. In this study, fluorescent retrograde tracers were injected into ACC, mPFC and OFC, and labeled cells were identified in the cholinergic nucleus basalis of Meynert (NBM and noradrenergic nucleus locus coeruleus (LC. Injections into all three cortical regions consistently labeled cells primarily ipsilateral to the injection site with a minimal contralateral component. In NBM, retrogradely labeled neurons were scattered throughout the rostral half of the nucleus, whereas those in LC tended to cluster in the core of the nucleus, and were rarely localized within the rostral or caudal poles. In NBM, more than half of all retrogradely labeled cells possessed axon collaterals projecting two or more PFC subregions. In LC, however, only 4.3% of retrogradely labeled neurons possessed collaterals targeting any two prefrontal subregions simultaneously, and no cells were identified that projected to all three regions. Of all labeled LC neurons, 49.3% projected only to mPFC, 28.5% projected only to OFC, and 18.0% projected only to ACC. These findings suggest that subsets of LC neurons may be capable of modulating neuronal activity in individual prefrontal subregions independently, whereas assemblies of NBM cells may exert

  4. Effects of 12-Week Bacopa monnieri Consumption on Attention, Cognitive Processing, Working Memory, and Functions of Both Cholinergic and Monoaminergic Systems in Healthy Elderly Volunteers

    Directory of Open Access Journals (Sweden)

    Tatimah Peth-Nui

    2012-01-01

    Full Text Available At present, the scientific evidence concerning the effect of Bacopa monnieri on brain activity together with working memory is less available. Therefore, we aimed to determine the effect of B. monnieri on attention, cognitive processing, working memory, and cholinergic and monoaminergic functions in healthy elderly. A randomized double-blind placebo-controlled design was utilized. Sixty healthy elderly subjects (mean age 62.62 years; SD 6.46, consisting of 23 males and 37 females, received either a standardized extract of B. monnieri (300 and 600 mg or placebo once daily for 12 weeks. The cholinergic and monoaminergic systems functions were determined using AChE and MAO activities. Working memory was assessed using percent accuracy and reaction time of various memory tests as indices, whereas attention and cognitive processing were assessed using latencies and amplitude of N100 and P300 components of event-related potential. All assessments were performed before treatment, every four weeks throughout study period, and at four weeks after the cessation of intervention. B. monnieri-treated group showed improved working memory together with a decrease in both N100 and P300 latencies. The suppression of plasma AChE activity was also observed. These results suggest that B. monnieri can improve attention, cognitive processing, and working memory partly via the suppression of AChE activity.

  5. The influence of the boost in breast-conserving therapy on cosmetic outcome in the EORTC 'boost versus no boost' trial

    International Nuclear Information System (INIS)

    Purpose: To evaluate the influence of a radiotherapy boost on the cosmetic outcome after 3 years of follow-up in patients treated with breast-conserving therapy (BCT). Methods and Materials: In EORTC trial 22881/10882, 5569 Stage I and II breast cancer patients were treated with tumorectomy and axillary dissection, followed by tangential irradiation of the breast to a dose of 50 Gy in 5 weeks, at 2 Gy per fraction. Patients having a microscopically complete tumor excision were randomized between no boost and a boost of 16 Gy. The cosmetic outcome was evaluated by a panel, scoring photographs of 731 patients taken soon after surgery and 3 years later, and by digitizer measurements, measuring the displacement of the nipple of 3000 patients postoperatively and of 1141 patients 3 years later. Results: There was no difference in the cosmetic outcome between the two treatment arms after surgery, before the start of radiotherapy. At 3-year follow-up, both the panel evaluation and the digitizer measurements showed that the boost had a significant adverse effect on the cosmetic result. The panel evaluation at 3 years showed that 86% of patients in the no-boost group had an excellent or good global result, compared to 71% of patients in the boost group (p = 0.0001). The digitizer measurements at 3 years showed a relative breast retraction assessment (pBRA) of 7.6 pBRA in the no-boost group, compared to 8.3 pBRA in the boost group, indicating a worse cosmetic result in the boost group at follow-up (p = 0.04). Conclusions: These results showed that a boost dose of 16 Gy had a negative, but limited, impact on the cosmetic outcome after 3 years

  6. Biological targets of cholinergic pesticides and possible use of alternative models for toxicity testing

    OpenAIRE

    C Falugi; Z. Rakonczay; M.G. Aluigi

    2011-01-01

    The use of protection plant products for the control of pests in agriculture should be accompanied by a clear understanding of possible damages to human and environmental health. The mechanisms of action and the affects on developing organisms exerted by acute and chronic exposure to the main classes of cholinergic pesticides are reviewed.

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

    NARCIS (Netherlands)

    DEBOER, P; WESTERINK, BHC

    1994-01-01

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

  8. Pitx3 deficiency in mice affects cholinergic modulation of GABAergic synapses in the nucleus accumbens

    NARCIS (Netherlands)

    de Rover, Mischa; Lodder, Johannes C.; Smidt, Marten P.; Brussaard, Arjen B.

    2006-01-01

    Pitx3 deficiency in mice affects cholinergic modulation of GABAergic synapses in the nucleus accumbens. J Neurophysiol 96: 2034-2041, 2006. First published July 12, 2006; doi:10.1152/jn.00333.2006. We investigated to what extent Pitx3 deficiency, causing hyperdopaminergic transmission in the nucleus

  9. An autoradiographic analysis of cholinergic receptors in mouse brain after chronic nicotine treatment

    International Nuclear Information System (INIS)

    Quantitative autoradiographic procedures were used to examine the effects of chronic nicotine infusion on the number of central nervous system nicotinic cholinergic receptors. Female DBA mice were implanted with jugular cannulas and infused with saline or various doses of nicotine (0.25, 0.5, 1.0 or 2.0 mg/kg/hr) for 10 days. The animals were then sacrificed and the brains were removed and frozen in isopentane. Cryostat sections were collected and prepared for autoradiographic procedures as previously described. Nicotinic cholinergic receptors were labeled with L-[3H]nicotine or alpha-[125I]bungarotoxin; [3H]quinuclidinyl benzilate was used to measure muscarinic cholinergic receptor binding. Chronic nicotine infusion increased the number of sites labeled by [3H]nicotine in most brain areas. However, the extent of the increase in binding as well as the dose-response curves for the increase were widely different among brain regions. After the highest treatment dose, binding was increased in 67 of 86 regions measured. Septal and thalamic regions were most resistant to change. Nicotinic binding measured by alpha-[125I]bungarotoxin also increased after chronic treatment, but in a less robust fashion. At the highest treatment dose, only 26 of 80 regions were significantly changes. Muscarinic binding was not altered after chronic nicotine treatment. These data suggest that brain regions are not equivalent in the mechanisms that regulate alterations in nicotinic cholinergic receptor binding after chronic nicotine treatment

  10. Cholinergic axon length reduced by 300 meters in the brain of an Alzheimer mouse model

    DEFF Research Database (Denmark)

    Nikolajsen, Gitte; Jensen, Morten Skovgaard; West, Mark J.

    2011-01-01

    Modern stereological techniques have been used to show that the total length of the cholinergic fibers in the cerebral cortex of the APPswe/PS1deltaE9 mouse is reduced by almost 300 meters at 18 months of age and has a nonlinear relationship to the amount of transgenetically-induced amyloidosis...

  11. Cholinergic Modulation during Acquisition of Olfactory Fear Conditioning Alters Learning and Stimulus Generalization in Mice

    Science.gov (United States)

    Pavesi, Eloisa; Gooch, Allison; Lee, Elizabeth; Fletcher, Max L.

    2013-01-01

    We investigated the role of cholinergic neurotransmission in olfactory fear learning. Mice receiving pairings of odor and foot shock displayed fear to the trained odor the following day. Pretraining injections of the nicotinic antagonist mecamylamine had no effect on subsequent freezing, while the muscarinic antagonist scopolamine significantly…

  12. Cholinergic modulation of the cerebral metabolic response to citalopram in Alzheimer's disease

    OpenAIRE

    Smith, Gwenn S.; Kramer, Elisse; Ma, Yilong; Hermann, Carol R.; Dhawan, Vijay; Chaly, Thomas; Eidelberg, David

    2009-01-01

    Pre-clinical and human neuropharmacological evidence suggests a role of cholinergic modulation of monoamines as a pathophysiological and therapeutic mechanism in Alzheimer's disease. The present study measured the effects of treatment with the cholinesterase inhibitor and nicotinic receptor modulator, galantamine, on the cerebral metabolic response to the selective serotonin reuptake inhibitor, citalopram. Seven probable Alzheimer's disease patients and seven demographically comparable contro...

  13. Hippocampal “cholinergic interneurons” visualized with the choline acetyltransferase promoter: anatomical distribution, intrinsic membrane properties, neurochemical characteristics, and capacity for cholinergic modulation

    Directory of Open Access Journals (Sweden)

    Feng Yi

    2015-03-01

    Full Text Available Release of acetylcholine (ACh in the hippocampus (HC occurs during exploration, arousal, and learning. Although the medial septum-diagonal band of Broca (MS-DBB is the major extrinsic source of cholinergic input to the HC, cholinergic neurons intrinsic to the HC also exist but remain poorly understood. Here, ChAT-tauGFP and ChAT-CRE/Rosa26YFP (ChAT-Rosa mice were examined in HC. The HC of ChAT-tauGFP mice was densely innervated with GFP-positive axons, often accompanied by large GFP-positive structures, some of which were Neurotrace/DAPI-negative and likely represent large axon terminals. In the HC of ChAT-Rosa mice, ChAT-YFP cells were Neurotrace-positive and more abundant in CA3 and dentate gyrus than CA1 with partial overlapping with calretinin/VIP. Moreover, an anti-ChAT antibody consistently showed ChAT immunoreactivity in ChAT-YFP cells from MS-DBB but rarely from HC. Furthermore, ChAT-YFP cells from CA1 stratum radiatum/stratum lacunosum moleculare (SR/SLM exhibited a stuttering firing phenotype but a delayed firing phenotype in stratum pyramidale (SP of CA3. Input resistance and capacitance were also different between CA1 SR/LM and CA3 SP ChAT-YFP cells. Bath application of ACh increased firing frequency in all ChAT-YFP cells; however, cholinergic modulation was larger in CA1 SR/SLM than CA3 SP ChAT-YFP cells. Finally, CA3 SP ChAT-YFP cells exhibited a wider AP half-width and weaker cholinergic modulation than YFP-negative CA3 pyramidal cells. Consistent with CRE expression in a subpopulation of principal cells, optogenetic stimulation evoked glutamatergic postsynaptic currents in CA1 SR/SLM interneurons. In conclusion, the presence of fluorescently labeled hippocampal cells common to both ChAT-Rosa and ChAT-tauGFP mice are in good agreement with previous reports on the existence of cholinergic interneurons, but both transgenic mouse lines exhibited unexpected anatomical features that departed considerably from earlier observations.

  14. Boost matrix converters in clean energy systems

    Science.gov (United States)

    Karaman, Ekrem

    This dissertation describes an investigation of novel power electronic converters, based on the ultra-sparse matrix topology and characterized by the minimum number of semiconductor switches. The Z-source, Quasi Z-source, Series Z-source and Switched-inductor Z-source networks were originally proposed for boosting the output voltage of power electronic inverters. These ideas were extended here on three-phase to three-phase and three-phase to single-phase indirect matrix converters. For the three-phase to three-phase matrix converters, the Z-source networks are placed between the three-switch input rectifier stage and the output six-switch inverter stage. A brief shoot-through state produces the voltage boost. An optimal pulse width modulation technique was developed to achieve high boosting capability and minimum switching losses in the converter. For the three-phase to single-phase matrix converters, those networks are placed similarly. For control purposes, a new modulation technique has been developed. As an example application, the proposed converters constitute a viable alternative to the existing solutions in residential wind-energy systems, where a low-voltage variable-speed generator feeds power to the higher-voltage fixed-frequency grid. Comprehensive analytical derivations and simulation results were carried out to investigate the operation of the proposed converters. Performance of the proposed converters was then compared between each other as well as with conventional converters. The operation of the converters was experimentally validated using a laboratory prototype.

  15. A Composite PWM Control Strategy for Boost Converter

    Science.gov (United States)

    Qingfeng, Liu; Zhaoxia, Leng; Jinkun, Sun; Huamin, Wang

    In order to improve the control performance of boost converter with large signal disturbance, a composite PWM control strategy for boost converter operating in continuous condition mode (CCM) was proposed in this paper. The parasitical loss of Boost converter was analyzed and a loss compensation strategy was adopted to design feed-forward tracker for converter. The composite PWM controller consisted of the tracker and PID controller. Simulation and experiment results validated the validity of the control strategy presented in this paper.

  16. Boosted Neural Networks in Evolutionary Computation

    Czech Academy of Sciences Publication Activity Database

    Holeňa, Martin; Linke, D.; Steinfeldt, N.

    Berlin : Springer, 2009 - (Leung, C.; Lee, M.; Chan, J.), s. 131-140 ISBN 978-3-642-10682-8. - (Lecture Notes in Computer Science. 5864). [ICONIP 2009. International Conference on Neural Information Processing /16./. Bangkok (TH), 01.12.2009-05.12.2009] R&D Projects: GA ČR GA201/08/0802; GA ČR GEICC/08/E018 Institutional research plan: CEZ:AV0Z10300504 Keywords : evolutionary algorithms * empirical objective functions * surrogate modelling * surrogate modelling * artificial neural network s * boosting Subject RIV: IN - Informatics, Computer Science

  17. Zhenhai to Boost Crude on Rising Demand

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    @@ Zhenhai Refining & Chemical plans to boost July crude throughput by at least 5 percent from June due to expectations of a rise in domestic demand, an industry official said on June 24. The forecast July level could match the refinery's April throughput at 1.06 million tons, the highest so far in 2003, an official close to the refinery's operations said, adding "China could see a big rise in demand from domestic travels next month especially after Beijing was dropped off the travel warning list."

  18. Boosted Surrogate Models in Evolutionary Optimization

    Czech Academy of Sciences Publication Activity Database

    Holeňa, Martin

    Seňa : Pont, 2009 - (Vojtáš, P.), s. 15-22 ISBN 978-80-970179-2-7. [ITAT 2009. Conference on Theory and Practice of Information Theory. Kráľova studňa (SK), 25.09.2009-29.09.2009] R&D Projects: GA ČR GA201/08/1744 Institutional research plan: CEZ:AV0Z10300504 Keywords : evolutionary optimization * genetic algorithms * surrogate modelling * regression models * boosting Subject RIV: IN - Informatics, Computer Science

  19. BOOSTING CED USING ROBUST ORIENTATION ESTIMATION

    Directory of Open Access Journals (Sweden)

    Tariq M. Khan

    2014-05-01

    Full Text Available In this paper, Coherence Enhancement Diffusion (CED is boosted feeding external orientation using new robust orientation estimation. In CED, proper scale selection is very important as the gradient vector at that scale reflects the orientation of local ridge. For this purpose a new scheme is proposed in which pre calculated orientation, by using local and integration scales. From the experiments it is found the proposed scheme is working much better in noisy environment as compared to the traditional Coherence Enhancement Diffusion

  20. Nanophotonic boost of intermolecular energy transfer

    CERN Document Server

    de Roque, P M; Sapienza, R

    2015-01-01

    We propose a scheme for efficient long-range energy transfer between two distant light emitters separated by more than one wavelength of light, i.e. much beyond the classical Forster radius. A hybrid nanoantenna-waveguide system mediates the transmission of energy, showing enhancements up to 10^8 as compared to vacuum. Our model shows how energy transfer in nanostructured media can be boosted, beyond the simple donor Purcell enhancement, and in particular for large donor-acceptor separations. The scheme we propose connects realistic emitters and could lead to practical on-chip implementations.

  1. Mixed Lorentz boosted $Z^{0}'s$

    CERN Document Server

    Kjaer, N J

    2001-01-01

    A novel technique is proposed to study systematic errors on jet reconstruction in W physics measurements at LEP2 with high statistical precision. The method is based on the emulation of W pair events using Mixed Lorentz Boosted Z0 events. The scope and merits of the method and its statistical accuracy are discussed in the context of the DELPHI W mass measurement in the fully hadronic channel. The numbers presented are preliminary in the sense that they do not constitute the final DELPHI systematic errors.

  2. Potentiation of NMDA receptor-mediated transmission in striatal cholinergic interneurons.

    Science.gov (United States)

    Oswald, Manfred J; Schulz, Jan M; Kelsch, Wolfgang; Oorschot, Dorothy E; Reynolds, John N J

    2015-01-01

    Pauses in the tonic firing of striatal cholinergic interneurons (CINs) emerge during reward-related learning in response to conditioning of a neutral cue. We have previously reported that augmenting the postsynaptic response to cortical afferents in CINs is coupled to the emergence of a cell-intrinsic afterhyperpolarization (AHP) underlying pauses in tonic activity. Here we investigated in a bihemispheric rat-brain slice preparation the mechanisms of synaptic plasticity of excitatory afferents to CINs and the association with changes in the AHP. We found that high frequency stimulation (HFS) of commissural corticostriatal afferents from the contralateral hemisphere induced a robust long-term depression (LTD) of postsynaptic potentials (PSP) in CINs. Depression of the PSP of smaller magnitude and duration was observed in response to HFS of the ipsilateral white matter or cerebral cortex. In Mg(2+)-free solution HFS induced NMDA receptor-dependent potentiation of the PSP, evident in both the maximal slope and amplitude of the PSP. The increase in maximal slope corroborates previous findings, and was blocked by antagonism of either D1-like dopamine receptors with SCH23390 or D2-like dopamine receptors with sulpiride during HFS in Mg(2+)-free solution. Potentiation of the slower PSP amplitude component was due to augmentation of the NMDA receptor-mediated potential as this was completely reversed on subsequent application of the NMDA receptor antagonist AP5. HFS similarly potentiated NMDA receptor currents isolated by blockade of AMPA/kainate receptors with CNQX. The plasticity-induced increase in the slow PSP component was directly associated with an increase in the subsequent AHP. Thus plasticity of cortical afferent synapses is ideally suited to influence the cue-induced firing dynamics of CINs, particularly through potentiation of NMDA receptor-mediated synaptic transmission. PMID:25914618

  3. The placental cholinergic system: localization to the cytotrophoblast and modulation of nitric oxide

    Directory of Open Access Journals (Sweden)

    Fant Michael E

    2006-05-01

    Full Text Available Abstract Background The human placenta, a non-neuronal tissue, contains an active cholinergic system comprised of acetylcholine (ACh, choline acetyltransferase (ChAT, acetylcholinesterase (AChE, and high affinity muscarinic receptors. The cell(s of origin of placental ACh and its role in trophoblast function has not been defined. These studies were performed to define the cellular location of ACh synthesis (ChAT in the human placenta and to begin studying its functional role. Results Using immunohistochemical techniques, ChAT was observed primarily within the cytotrophoblasts of preterm placentae as well as some mesenchymal elements. Similar intense immunostaining of the cytotrophoblast was observed for endothelium-derived nitric oxide synthase (eNOS suggesting that ACh may interact with nitric oxide (NO-dependent signaling pathways. The ability of carbamylcholine (CCh, an ACh analogue, to stimulate a rise in intracellular Ca++ and NO production in trophoblasts was therefore tested using the BeWob30 choriocarcinoma cell as a model system. First, CCh significantly increased intracellular calcium as assessed by fluorescence microscopy. We then examined the ability of CCh to stimulate NO production by measuring total nitrite/nitrate production in conditioned media using chemiluminescence-based analysis. CCh, alone, had no effect on NO production. However, CCh increased measurable NO approximately 100% in the presence of 10 nM estradiol. This stimulatory effect was inhibited by 1 (microM scopolamine suggesting mediation via muscarinic receptors. Estradiol, alone, had no effect on total NO or eNOS protein or mRNA. Conclusion These data demonstrate that placental ChAT localizes to the cytotrophoblast and some mesenchymal cells in human placenta. It further suggests that ACh acts via muscarinic receptors on the trophoblast cell membrane to modulate NO in an estrogen-dependent manner.

  4. Neurofunctional imaging of the pancreas utilizing the cholinergic PET radioligand [18F]4-fluorobenzyltrozamicol

    International Nuclear Information System (INIS)

    The pancreas is one of the most heavily innervated peripheral organs in the body. Parasympathetic and sympathetic neurons terminate in the pancreas and provide tight control of endocrine and exocrine functions. The aim of this study was to determine whether the pancreas can be imaged with a radioligand that binds to specific neuroreceptors. Using fluorine-18 4-fluorobenzyltrozamicol (FBT), which binds to the presynaptic vesicular acetylcholine transporter, positron emission tomography scans were performed in four adult mice, two adult rhesus monkeys, and one adult human. In these mammals, the pancreas is intensely FBT avid, with uptake greater than in any other organ at 30, 60, and 90 min. The maximum standardized uptake value (SUV) ratios of pancreas to liver, for example, ranged from 1.4 to 1.7 in rhesus monkeys (mean 1.6; median 1.7) and from 1.9 to 4.7 (mean 3.24; median 3.02) in mice. The maximum SUV ratio of pancreas to liver in the human was 1.8. These data suggest that neuroreceptor imaging of the pancreas in vivo is feasible in animal models and humans. This imaging could allow researchers to interrogate functions under control of the autonomic nervous system in the pancreas, with applications possible in transplanted and native pancreata. Also, as beta cell function is intimately related to parasympathetic cholinergic input, FBT activity in the pancreas may correlate with insulin-producing beta cell mass. This could ultimately provide a method of in vivo imaging in animal models and humans for diabetes research. (orig.)

  5. Neurofunctional imaging of the pancreas utilizing the cholinergic PET radioligand [{sup 18}F]4-fluorobenzyltrozamicol

    Energy Technology Data Exchange (ETDEWEB)

    Clark, P.B.; Gage, H.D.; Brown-Proctor, C.; Buchheimer, N.; Morton, K.A. [Nuclear Medicine Section, Department of Radiology, Wake Forest University School of Medicine, Medical Center Blvd., NC 27157, Winston-Salem (United States); Calles-Escandon, J. [Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina (United States); Mach, R.H. [Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri (United States)

    2004-02-01

    The pancreas is one of the most heavily innervated peripheral organs in the body. Parasympathetic and sympathetic neurons terminate in the pancreas and provide tight control of endocrine and exocrine functions. The aim of this study was to determine whether the pancreas can be imaged with a radioligand that binds to specific neuroreceptors. Using fluorine-18 4-fluorobenzyltrozamicol (FBT), which binds to the presynaptic vesicular acetylcholine transporter, positron emission tomography scans were performed in four adult mice, two adult rhesus monkeys, and one adult human. In these mammals, the pancreas is intensely FBT avid, with uptake greater than in any other organ at 30, 60, and 90 min. The maximum standardized uptake value (SUV) ratios of pancreas to liver, for example, ranged from 1.4 to 1.7 in rhesus monkeys (mean 1.6; median 1.7) and from 1.9 to 4.7 (mean 3.24; median 3.02) in mice. The maximum SUV ratio of pancreas to liver in the human was 1.8. These data suggest that neuroreceptor imaging of the pancreas in vivo is feasible in animal models and humans. This imaging could allow researchers to interrogate functions under control of the autonomic nervous system in the pancreas, with applications possible in transplanted and native pancreata. Also, as beta cell function is intimately related to parasympathetic cholinergic input, FBT activity in the pancreas may correlate with insulin-producing beta cell mass. This could ultimately provide a method of in vivo imaging in animal models and humans for diabetes research. (orig.)

  6. Grid Connected Solar PV System with SEPIC Converter Compared with Parallel Boost Converter Based MPPT

    Directory of Open Access Journals (Sweden)

    T. Ajith Bosco Raj

    2014-01-01

    Full Text Available The main objective of this work is to study the behaviour of the solar PV systems and model the efficient Grid-connected solar power system. The DC-DC MPPT circuit using chaotic pulse width modulation has been designed to track maximum power from solar PV module. The conversion efficiency of the proposed MPPT system is increased when CPWM is used as a control scheme. This paper also proposes a simplified multilevel (seven level inverter for a grid-connected photovoltaic system. The primary goal of these systems is to increase the energy injected to the grid by keeping track of the maximum power point of the panel, by reducing the switching frequency, and by providing high reliability. The maximum power has been tracked experimentally. It is compared with parallel boost converter. Also this model is based on mathematical equations and is described through an equivalent circuit including a PV source with MPPT, a diode, a series resistor, a shunt resistor, and dual boost converter with active snubber circuit. This model can extract PV power and boost by using dual boost converter with active snubber. By using this method the overall system efficiency is improved thereby reducing the switching losses and cost.

  7. Boost Converters for Gas Electric and Fuel Cell Hybrid Electric Vehicles

    Energy Technology Data Exchange (ETDEWEB)

    McKeever, JW

    2005-06-16

    of the switch mode boost converter is its simplicity. Its inductor must handle the entire current, which is responsible for its main cost. The new Z-source inverter technology [2,3] boosts voltage directly by actively using the zero state time to boost the voltage. In the traditional pulse width modulated (PWM) inverter, this time is used only to control the average voltage by disconnecting the supply voltage from the motor. The purpose of this study is to examine the Z-source's potential for reducing the cost and improving the reliability of HEVs.

  8. INTRAHIPPOCAMPAL ADMINISTRATION OF IBOTENIC ACID INDUCED CHOLINERGIC DYSFUNCTION via NR2A/NR2B EXPRESSION: IMPLICATIONS OF RESVERATROL AGAINST ALZHEIMER DISEASE PATHOPHYSIOLOGY

    Directory of Open Access Journals (Sweden)

    Chennakesavan eKarthick

    2016-04-01

    Full Text Available Although several drugs revealed moderate amelioration of symptoms, none of them have sufficient potency to prevent or reverse the progression towards Alzheimer’s disease (AD pathology. Resveratrol (RSV, a polyphenolic compound has shown an outstanding therapeutic effect on a broad spectrum of diseases like age-associated neurodegeneration, inflammation etc. The present study was thus conducted to assess the therapeutic efficacy of RSV in ameliorating the deleterious effects of Ibotenic acid (IBO in male Wistar rats. Stereotactic intrahippocampal administration of IBO (5µg/µl lesioned rats impairs cholinergic transmission, learning and memory performance that is rather related to AD and thus chosen as a suitable model to understand the drug efficacy in preventing AD pathophysiology. Since IBO is an agonist of glutamate, it is expected to exhibit an excitotoxic effect by altering glutamatergic receptors like NMDA receptor. The current study displayed significant alterations in the mRNA expression of NR2A and NR2B subunits of NMDA receptors, and further it is surprising to note that cholinergic receptors decreased in expression particularly α7-nAChR with increased m1AChR. RSV administration (20mg/kg body weight, i.p significantly reduced these changes in IBO induced rats. Glutamatergic and cholinergic receptor alterations were associated with significant changes in the behavioral parameters of rats induced by IBO. While RSV improved spatial learning performance, attenuated immobility and improvised open field activity in IBO induced rats. NR2B activation in the present study might mediate cell death through oxidative stress that form the basis of abnormal behavioral pattern in IBO induced rats. Interestingly, RSV that could efficiently encounter oxidative stress have significantly decreased stress markers viz., nitrite, PCO, and MDA levels by enhancing antioxidant status. Histopathological analysis displayed significant reduction in the

  9. Intrahippocampal Administration of Ibotenic Acid Induced Cholinergic Dysfunction via NR2A/NR2B Expression: Implications of Resveratrol against Alzheimer Disease Pathophysiology.

    Science.gov (United States)

    Karthick, Chennakesavan; Periyasamy, Sabapathy; Jayachandran, Kesavan S; Anusuyadevi, Muthuswamy

    2016-01-01

    Although several drugs revealed moderate amelioration of symptoms, none of them have sufficient potency to prevent or reverse the progression toward Alzheimer's disease (AD) pathology. Resveratrol (RSV), a polyphenolic compound has shown an outstanding therapeutic effect on a broad spectrum of diseases like age-associated neurodegeneration, inflammation etc. The present study was thus conducted to assess the therapeutic efficacy of RSV in ameliorating the deleterious effects of Ibotenic acid (IBO) in male Wistar rats. Stereotactic intrahippocampal administration of IBO (5 μg/μl) lesioned rats impairs cholinergic transmission, learning and memory performance that is rather related to AD and thus chosen as a suitable model to understand the drug efficacy in preventing AD pathophysiology. Since IBO is an agonist of glutamate, it is expected to exhibit an excitotoxic effect by altering glutamatergic receptors like NMDA receptor. The current study displayed significant alterations in the mRNA expression of NR2A and NR2B subunits of NMDA receptors, and further it is surprising to note that cholinergic receptors decreased in expression particularly α7-nAChR with increased m1AChR. RSV administration (20 mg/kg body weight, i.p.) significantly reduced these changes in IBO induced rats. Glutamatergic and cholinergic receptor alterations were associated with significant changes in the behavioral parameters of rats induced by IBO. While RSV improved spatial learning performance, attenuated immobility, and improvised open field activity in IBO induced rats. NR2B activation in the present study might mediate cell death through oxidative stress that form the basis of abnormal behavioral pattern in IBO induced rats. Interestingly, RSV that could efficiently encounter oxidative stress have significantly decreased stress markers viz., nitrite, PCO, and MDA levels by enhancing antioxidant status. Histopathological analysis displayed significant reduction in the hippocampal

  10. An update on Shankhpushpi, a cognition-boosting Ayurvedic medicine.

    Science.gov (United States)

    Sethiya, Neeraj Kumar; Nahata, Alok; Mishra, Sri Hari; Dixit, Vinod Kumar

    2009-11-01

    Shankhpushpi is an Ayurvedic drug used for its action on the central nervous system, especially for boosting memory and improving intellect. Quantum of information gained from Ayurvedic and other Sanskrit literature revealed the existence of four different plant species under the name of Shankhpushpi, which is used in various Ayurvedic prescriptions described in ancient texts, singly or in combination with other herbs. The sources comprise of entire herbs with following botanicals viz., Convulvulus pluricaulis Choisy. (Convulvulaceae), Evolvulus alsinoides Linn. (Convulvulaceae), Clitoria ternatea Linn. (Papilionaceae) and Canscora decussata Schult. (Gentianaceae). A review on the available scientific information in terms of pharmacognostical characteristics, chemical constituents, pharmacological activities, preclinical and clinical applications of controversial sources of Shankhpushpi is prepared with a view to review scientific work undertaken on Shankhpushpi. It may provide parameters of differentiation and permit appreciation of variability of drug action by use of different botanical sources. PMID:19912732

  11. Muscarinic Receptor Activation Elicits Sustained, Recurring Depolarizations in Reticulospinal Neurons

    OpenAIRE

    Smetana, R. W.; Alford, S.; Dubuc, R.

    2007-01-01

    In lampreys, brain stem reticulospinal (RS) neurons constitute the main descending input to the spinal cord and activate the spinal locomotor central pattern generators. Cholinergic nicotinic inputs activate RS neurons, and consequently, induce locomotion. Cholinergic muscarinic agonists also induce locomotion when applied to the brain stem of birds. This study examined whether bath applications of muscarinic agonists could activate RS neurons and initiate motor output in lampreys. Bath appli...

  12. Cerebrolysin modulates pronerve growth factor/nerve growth factor ratio and ameliorates the cholinergic deficit in a transgenic model of Alzheimer's disease.

    Science.gov (United States)

    Ubhi, Kiren; Rockenstein, Edward; Vazquez-Roque, Ruben; Mante, Michael; Inglis, Chandra; Patrick, Christina; Adame, Anthony; Fahnestock, Margaret; Doppler, Edith; Novak, Philip; Moessler, Herbert; Masliah, Eliezer

    2013-02-01

    Alzheimer's disease (AD) is characterized by degeneration of neocortex, limbic system, and basal forebrain, accompanied by accumulation of amyloid-β and tangle formation. Cerebrolysin (CBL), a peptide mixture with neurotrophic-like effects, is reported to improve cognition and activities of daily living in patients with AD. Likewise, CBL reduces synaptic and behavioral deficits in transgenic (tg) mice overexpressing the human amyloid precursor protein (hAPP). The neuroprotective effects of CBL may involve multiple mechanisms, including signaling regulation, control of APP metabolism, and expression of neurotrophic factors. We investigate the effects of CBL in the hAPP tg model of AD on levels of neurotrophic factors, including pro-nerve growth factor (NGF), NGF, brain-derived neurotrophic factor (BDNF), neurotropin (NT)-3, NT4, and ciliary neurotrophic factor (CNTF). Immunoblot analysis demonstrated that levels of pro-NGF were increased in saline-treated hAPP tg mice. In contrast, CBL-treated hAPP tg mice showed levels of pro-NGF comparable to control and increased levels of mature NGF. Consistently with these results, immunohistochemical analysis demonstrated increased NGF immunoreactivity in the hippocampus of CBL-treated hAPP tg mice. Protein levels of other neurotrophic factors, including BDNF, NT3, NT4, and CNTF, were unchanged. mRNA levels of NGF and other neurotrophins were also unchanged. Analysis of neurotrophin receptors showed preservation of the levels of TrKA and p75(NTR) immunoreactivity per cell in the nucleus basalis. Cholinergic cells in the nucleus basalis were reduced in the saline-treated hAPP tg mice, and treatment with CBL reduced these cholinergic deficits. These results suggest that the neurotrophic effects of CBL might involve modulation of the pro-NGF/NGF balance and a concomitant protection of cholinergic neurons. PMID:23152192

  13. Precision Jet Substructure from Boosted Event Shapes

    CERN Document Server

    Feige, Ilya; Stewart, Iain; Thaler, Jesse

    2012-01-01

    Jet substructure has emerged as a critical tool for LHC searches, but studies so far have relied heavily on shower Monte Carlos, which formally approximate QCD at leading-log level. We demonstrate that systematic higher-order QCD computations of jet substructure can be carried out by boosting global event shapes by a large momentum Q, and accounting for effects due to finite jet size, initial state radiation (ISR), and underlying event (UE) as 1/Q corrections. In particular, we compute the 2-subjettiness substructure distribution for boosted Z -> q qbar events at the LHC at next-to-next-to-next-to-leading log order. The calculation is greatly simplified by recycling known results for the thrust distribution in e+ e- collisions. The 2-subjettiness distribution quickly saturates, becoming Q independent for Q > 400 GeV. Crucially, the effects of jet contamination from ISR/UE can be subtracted out analytically at large Q, without knowing their detailed form. Amusingly, the Q=infinity and Q=0 distributions are rel...

  14. A Magnetohydrodynamic Boost for Relativistic Jets

    Science.gov (United States)

    Mizuno, Yosuke; Hardee, Philip; Hartmann, Dieter H.; Nishikawa, Ken-Ichi; Zhang, Bing

    2007-01-01

    We performed relativistic magnetohydrodynamic simulations of the hydrodynamic boosting mechanism for relativistic jets explored by Aloy & Rezzolla (2006) using the RAISHIN code. Simulation results show that the presence of a magnetic field changes the properties of the shock interface between the tenuous, overpressured jet (V^z j) flowing tangentially to a dense external medium. We find that magnetic fields can lead to more efficient acceleration of the jet, in comparison to the pure-hydrodynamic case. A "poloidal" magnetic field (B^z), tangent to the interface and parallel to the jet flow, produces both a stronger outward moving shock and a stronger inward moving rarefaction wave. This leads to a large velocity component normal to the interface in addition to acceleration tangent to the interface, and the jet is thus accelerated to larger Lorentz factors than those obtained in the pure-hydrodynamic case. Likewise, a strong "toroidal" magnetic field (B^y), tangent to the interface but perpendicular to the jet flow, also leads to stronger acceleration tangent to the shock interface relative to the pure-hydrodynamic case. Thus. the presence and relative orientation of a magnetic field in relativistic jets can significant modify the hydrodynamic boost mechanism studied by Aloy & Rezzolla (2006).

  15. A multiview boosting approach to tissue segmentation

    Science.gov (United States)

    Kwak, Jin Tae; Xu, Sheng; Pinto, Peter A.; Turkbey, Baris; Bernardo, Marcelino; Choyke, Peter L.; Wood, Bradford J.

    2014-04-01

    Digitized histopathology images have a great potential for improving or facilitating current assessment tools in cancer pathology. In order to develop accurate and robust automated methods, the precise segmentation of histologic objects such epithelium, stroma, and nucleus is necessary, in the hopes of information extraction not otherwise obvious to the subjective eye. Here, we propose a multivew boosting approach to segment histology objects of prostate tissue. Tissue specimen images are first represented at different scales using a Gaussian kernel and converted into several forms such HSV and La*b*. Intensity- and texture-based features are extracted from the converted images. Adopting multiview boosting approach, we effectively learn a classifier to predict the histologic class of a pixel in a prostate tissue specimen. The method attempts to integrate the information from multiple scales (or views). 18 prostate tissue specimens from 4 patients were employed to evaluate the new method. The method was trained on 11 tissue specimens including 75,832 epithelial and 103,453 stroma pixels and tested on 55,319 epithelial and 74,945 stroma pixels from 7 tissue specimens. The technique showed 96.7% accuracy, and as summarized into a receiver operating characteristic (ROC) plot, the area under the ROC curve (AUC) of 0.983 (95% CI: 0.983-0.984) was achieved.

  16. Boosted Higgs boson tagging using jet substructures

    CERN Document Server

    Shvydkin, Pavel

    2016-01-01

    Searching BSM particles via the Higgs boson final state has now become common. The mass of desired BSM particle is more than 1 TeV, thereby its decay products are highly Lorentz-boosted. Hence the jets from b quark-antiquark pair - which the Higgs boson mostly decays into - are very closed to each other, and merged into one jet, that is typically reconstructed using large jet sizes (∆R = 0.8). In this work regression technique is applied to AK8 jets (which defined by anti-kT algorithm, using ΔR = 0.8). The regression makes use of boosted jets with substructure information, coupled with the pecularities of a b quark decay, like the presence of a soft lepton (SL) inside the jet. It has allowed to improve the resolution of the mass reconstruction and transverse momentum of the Higgs boson. This application results in improvement of the mass reconstruction by 3-4 percent. These result may be improved firstly by making more careful pileup rejection. Then it is possible to combine base regression train for dif...

  17. Cognitive disorder and changes in cholinergic receptors, N-methyl-D aspartate receptors, neural cell adhesion molecule, and brain-derived neurotrophic factor following brain injury

    Institute of Scientific and Technical Information of China (English)

    Weiliang Zhao; Dezhi Kang; Yuanxiang Lin

    2008-01-01

    BACKGROUND: Learning and memory damage is one of the most permanent and the severest symptoms of traumatic brain injury; it can seriously influence the normal life and work of patients. Some research has demonstrated that cognitive disorder is closely related to nicotine cholinergic receptors, N-methyl-D aspartate receptors, neural cell adhesion molecule, and brain-derived neurotrophic factor. OBJECTIVE: To summarize the cognitive disorder and changes in nicotine cholinergic receptors, N-methyl-D aspartate receptors, neural cell adhesion molecule, and brain-derived neurotrophic factor following brain injury. RETRIEVAL STRATEGY: A computer-based online search was conducted in PUBMED for English language publications containing the key words "brain injured, cognitive handicap, acetylcholine, N-methyl-D aspartate receptors, neural cell adhesion molecule, brain-derived neurotrophic factor" from January 2000 to December 2007. There were 44 papers in total. Inclusion criteria: ① articles about changes in nicotine cholinergic receptors, N-methyl-D aspartate receptors, neural cell adhesion molecule, and brain-derived neurotrophic factor following brain injury; ② articles in the same researching circle published in authoritative journals or recently published. Exclusion criteria: duplicated articles.LITERATURE EVALUATION: References were mainly derived from research on changes in these four factors following brain injury. The 20 included papers were clinical or basic experimental studies. DATA SYNTHESIS: After craniocerebral injury, changes in these four factors in brain were similar to those during recovery from cognitive disorder, to a certain degree. Some data have indicated that activation of nicotine cholinergic receptors, N-methyl-D aspartate receptors, neural cell adhesion molecule, and brain-derived neurotrophic factor could greatly improve cognitive disorder following brain injury. However, there are still a lot of questions remaining; for example, how do these

  18. Age-dependent loss of cholinergic neurons in learning and memory-related brain regions and impaired learning in SAMP8 mice with trigeminal nerve damage

    Institute of Scientific and Technical Information of China (English)

    Yifan He; Jihong Zhu; Fang Huang; Liu Qin; Wenguo Fan; Hongwen He

    2014-01-01

    The tooth belongs to the trigeminal sensory pathway. Dental damage has been associated with impairments in the central nervous system that may be mediated by injury to the trigeminal nerve. In the present study, we investigated the effects of damage to the inferior alveolar nerve, an important peripheral nerve in the trigeminal sensory pathway, on learning and memory be-haviors and structural changes in related brain regions, in a mouse model of Alzheimer’s disease. Inferior alveolar nerve transection or sham surgery was performed in middle-aged (4-month-old) or elderly (7-month-old) senescence-accelerated mouse prone 8 (SAMP8) mice. When the middle-aged mice reached 8 months (middle-aged group 1) or 11 months (middle-aged group 2), and the elderly group reached 11 months, step-down passive avoidance and Y-maze tests of learn-ing and memory were performed, and the cholinergic system was examined in the hippocampus (Nissl staining and acetylcholinesterase histochemistry) and basal forebrain (choline acetyltrans-ferase immunohistochemistry). In the elderly group, animals that underwent nerve transection had fewer pyramidal neurons in the hippocampal CA1 and CA3 regions, fewer cholinergic ifbers in the CA1 and dentate gyrus, and fewer cholinergic neurons in the medial septal nucleus and vertical limb of the diagonal band, compared with sham-operated animals, as well as showing impairments in learning and memory. Conversely, no signiifcant differences in histology or be-havior were observed between middle-aged group 1 or group 2 transected mice and age-matched sham-operated mice. The present ifndings suggest that trigeminal nerve damage in old age, but not middle age, can induce degeneration of the septal-hippocampal cholinergic system and loss of hippocampal pyramidal neurons, and ultimately impair learning ability. Our results highlight the importance of active treatment of trigeminal nerve damage in elderly patients and those with Alzheimer’s disease, and

  19. Involvement of nicotinic and muscarinic receptors in the endogenous cholinergic modulation of the balance between excitation and inhibition in the young rat visual cortex.

    Science.gov (United States)

    Lucas-Meunier, Estelle; Monier, Cyril; Amar, Muriel; Baux, Gérard; Frégnac, Yves; Fossier, Philippe

    2009-10-01

    This study aims to clarify how endogenous release of cortical acetylcholine (ACh) modulates the balance between excitation and inhibition evoked in visual cortex. We show that electrical stimulation in layer 1 produced a significant release of ACh measured intracortically by chemoluminescence and evoked a composite synaptic response recorded intracellularly in layer 5 pyramidal neurons of rat visual cortex. The pharmacological specificity of the ACh neuromodulation was determined from the continuous whole-cell voltage clamp measurement of stimulation-locked changes of the input conductance during the application of cholinergic agonists and antagonists. Blockade of glutamatergic and gamma-aminobutyric acid (GABAergic) receptors suppressed the evoked response, indicating that stimulation-induced release of ACh does not directly activate a cholinergic synaptic conductance in recorded neurons. Comparison of cytisine and mecamylamine effects on nicotinic receptors showed that excitation is enhanced by endogenous evoked release of ACh through the presynaptic activation of alpha(*)beta4 receptors located on glutamatergic fibers. DHbetaE, the selective alpha4beta2 nicotinic receptor antagonist, induced a depression of inhibition. Endogenous ACh could also enhance inhibition by acting directly on GABAergic interneurons, presynaptic to the recorded cell. We conclude that endogenous-released ACh amplifies the dominance of the inhibitory drive and thus decreases the excitability and sensory responsiveness of layer 5 pyramidal neurons. PMID:19176636

  20. Hook-up of GluA2, GRIP and liprin-α for cholinergic muscarinic receptor-dependent LTD in the hippocampus

    Directory of Open Access Journals (Sweden)

    Wu Long-Jun

    2009-06-01

    Full Text Available Abstract The molecular mechanism underlying muscarinic acetylcholine receptor-dependent LTD (mAChR-LTD in the hippocampus is less studied. In a recent study, a novel mechanism is described. The induction of mAChR-LTD required the activation of protein tyrosine phosphatase (PTP, and the expression was mediated by AMPA receptor endocytosis via interactions between GluA2, GRIP and liprin-α. The hook-up of these proteins may result in the recruitment of leukocyte common antigen-related receptor (LAR, a PTP that is known to be involved in AMPA receptor trafficking. Interestingly, the similar molecular interaction cannot be applied to mGluR-LTD, despite the fact that the same G-protein involved in LTD is activated by both mAChR and mGluR. This discovery provides key molecular insights for cholinergic dependent cognitive function, and mAChR-LTD can serve as a useful cellular model for studying the roles of cholinergic mechanism in learning and memory.

  1. Posttraining infusion of cholinergic drugs into the ventral subiculum modulated memory in an inhibitory avoidance task: interaction with the bed nucleus of the stria terminalis.

    Science.gov (United States)

    Liu, Tzu-Lan; Liang, K C

    2009-03-01

    The ventral subiculum (vSUB), a hippocampal efferent target implicated in learning and stress coping, receives cholinergic input and sends glutamatergic output to the bed nucleus of the stria terminalis (BNST). This study examined the roles of vSUB muscarinic activation and its interaction with BNST N-methyl-D-aspartate and noradrenergic receptors in formation of aversive memory. Male Wistar rats with cannulae implanted into the vSUB or BNST were trained on a step-through inhibitory avoidance task. Shortly after training, they received cholinergic drugs infused into the vSUB and/or glutamatergic or noradrenergic drugs infused into the BNST. Results of the 1-day retention tests showed that intra-vSUB infusion of oxotremorine (0.01 microg) or scopolamine (0.3 or 3.0 microg) enhanced or impaired retention, respectively. Both effects were dose- and time-dependent, and 0.001 microg oxotremorine attenuated the amnesia induced by 3.0 microg scopolamine. The oxotremorine-induced memory enhancement was blocked by intra-BNST infusion of DL-2-amino-5-phosphonovaleric acid or propranolol at a dose not affecting retention; the amnesia induced by scopolamine was blunted by intra-BNST infusion of glutamate or norepinephrine at a dose with a negligible effect on retention. These data suggest that in an inhibitory avoidance task muscarinic activation of the vSUB modulated memory formation by interacting with the BNST glutamatergic and noradrenergic functions. PMID:19041726

  2. Power Factor Correction and THD Minimization by Interleaved Boost Converter in Continuous Conduction Mode

    Directory of Open Access Journals (Sweden)

    Saubhik Maulik

    2014-02-01

    Full Text Available The electrical energy available in the utility grid is not suitable for direct use in many applications. In particular, applications requiring DC source must involve an interface device between the AC power line and the load requiring the DC voltage. Conventional AC/DC conversion involves diode rectifiers with large capacitor to reduce DC voltage ripple. The filter capacitor reduces the ripple present in the output voltage but draws non-sinusoidal line current which reduces the power factor. So power factor correction (PFC techniques are gaining increasing attention. The most popular topology for active PFC is boost converter as it draws continuous input current. This input current can be manipulated by average current mode control technique. But there are ripple in the input current due to inductor of boost converter which can be minimized by using two phase interleaved boost converter. Here average current mode controlled interleaved boost converter in continuous conduction mode using PI controller, is represented which provides high power factor and low THD.

  3. Boosted objects: a probe of beyond the standard model physics

    DEFF Research Database (Denmark)

    Abdesselam, A.; Belyaev, A.; Kuutmann, E. B.;

    2011-01-01

    We present the report of the hadronic working group of the BOOST2010 workshop held at the University of Oxford in June 2010. The first part contains a review of the potential of hadronic decays of highly boosted particles as an aid for discovery at the LHC and a discussion of the status of tools ...

  4. Boost-rotation symmetric vacuum spacetimes with spinning sources

    OpenAIRE

    Pravdova, A.; Pravda, V.

    2001-01-01

    Boost-rotation symmetric vacuum spacetimes with spinning sources which correspond to gravitational field of uniformly accelerated spinning "particles" are studied. Regularity conditions and asymptotic properties are analyzed. News functions are derived by transforming the general spinning boost-rotation symmetric vacuum metric to Bondi-Sachs coordinates.

  5. Diode-Assisted Buck-Boost Current Source Inverters

    DEFF Research Database (Denmark)

    Gao, F.; Cai, Liang; Loh, P.C.; Blaabjerg, Frede

    This paper presents a couple of novel current source inverters (CSIs) with the enhanced current buckboost capability. With the unique diode-inductor network added between current source inverter circuitry and current boost elements, the proposed buck-boost current source inverters demonstrate a...

  6. Cholinergic neuronal lesions in the medial septum and vertical limb of the diagonal bands of Broca induce contextual fear memory generalization and impair acquisition of fear extinction.

    Science.gov (United States)

    Knox, Dayan; Keller, Samantha M

    2016-06-01

    Previous research has shown that the ventral medial prefrontal cortex (vmPFC) and hippocampus (Hipp) are critical for extinction memory. Basal forebrain (BF) cholinergic input to the vmPFC and Hipp is critical for neural function in these substrates, which suggests BF cholinergic neurons may be critical for extinction memory. In order to test this hypothesis, we applied cholinergic lesions to different regions of the BF and observed the effects these lesions had on extinction memory. Complete BF cholinergic lesions induced contextual fear memory generalization, and this generalized fear was resistant to extinction. Animals with complete BF cholinergic lesions could not acquire cued fear extinction. Restricted cholinergic lesions in the medial septum and vertical diagonal bands of Broca (MS/vDBB) mimicked the effects that BF cholinergic lesions had on contextual fear memory generalization and acquisition of fear extinction. Cholinergic lesions in the horizontal diagonal band of Broca and nucleus basalis (hDBB/NBM) induced a small deficit in extinction of generalized contextual fear memory with no accompanying deficits in cued fear extinction. The results of this study reveal that MS/vDBB cholinergic neurons are critical for inhibition and extinction of generalized contextual fear memory, and via this process, may be critical for acquisition of cued fear extinction. Further studies delineating neural circuits and mechanisms through which MS/vDBB cholinergic neurons facilitate these emotional memory processes are needed. © 2015 Wiley Periodicals, Inc. PMID:26606423

  7. Rescue of NGF-deficient mice II: basal forebrain cholinergic projections require NGF for target innervation but not guidance.

    Science.gov (United States)

    Phillips, Heidi S; Nishimura, Merry; Armanini, Mark P; Chen, Karen; Albers, Kathryn M; Davis, Brian M

    2004-04-29

    Basal forebrain cholinergic (BFC) neurons are an important substrate of cognitive function and are hypothesized to require the presence of nerve growth factor (NGF) for survival and target innervation. NGF-deficient mice develop BFC neurons that extend projections into telencephalic targets, but the mice perish before innervation is fully established. Rescue of NGF-deficient mice by transgenic expression of NGF under the keratin promoter yields viable mice with disrupted CNS expression of NGF. In the current study, rescued NGF-deficient mice contain normal numbers of septal cholinergic neurons yet reveal severe compromise of cholinergic innervation of both cortex and hippocampus. Surprisingly, intracerebroventricular infusion of NGF into juvenile mice can induce an essentially normal pattern of cholinergic innervation of the hippocampus. These results indicate that NGF is required for induction of proper innervation by BFC neurons, but that the cellular pattern of expression of this factor is not critical for specifying the distribution of axon terminals. PMID:15093680

  8. Application ofBoost Inverter to Multi Input PV system

    Directory of Open Access Journals (Sweden)

    G.SHINYVIKRAM

    2014-11-01

    Full Text Available With the shortage of the energy and ever increasing of the oil price, research on the renewable and green energy sources, especially the solar arrays and the fuel cells, becomes more and more important. How to achieve high step- up and high efficiency DC/DC converters is the major consideration in the renewable power applications due to the low voltage of PV arrays and fuel cells. The conventional boost converters increase the harmonics rate and add an extra stage of power conversion. This paper proposes a boost dc-ac inverter that can invert and boost the output voltage in a single stage. In this paper the proposed boost dc-ac inverter is applied to the solar power panels and is simulated using Simulink. The output results of the boost inverter are worthy promising.

  9. Elimination of the vesicular acetylcholine transporter in the striatum reveals regulation of behaviour by cholinergic-glutamatergic co-transmission.

    OpenAIRE

    Monica S Guzman; Xavier De Jaeger; Sanda Raulic; Souza, Ivana A; Li, Alex X.; Susanne Schmid; Menon, Ravi S.; Gainetdinov, Raul R.; Caron, Marc G.; Robert Bartha; Prado, Vania F.; Prado, Marco A. M.

    2011-01-01

    Cholinergic neurons in the striatum are thought to play major regulatory functions in motor behaviour and reward. These neurons express two vesicular transporters that can load either acetylcholine or glutamate into synaptic vesicles. Consequently cholinergic neurons can release both neurotransmitters, making it difficult to discern their individual contributions for the regulation of striatal functions. Here we have dissected the specific roles of acetylcholine release for striatal-dependent...

  10. Disposed to distraction: Genetic variation in the cholinergic system influences distractibility but not time-on-task effects

    OpenAIRE

    Berry, Anne S.; Demeter, Elise; Sabhapathy, Surya; English, Brett A.; Blakely, Randy D.; Sarter, Martin; Lustig, Cindy

    2014-01-01

    Both the passage of time and external distraction make it difficult to keep attention on the task at hand. We tested the hypothesis that time-on-task and external distraction pose independent challenges to attention, and that the brain’s cholinergic system selectively modulates our ability to resist distraction. Participants with a polymorphism limiting cholinergic capacity (Ile89Val variant (rs1013940) of the choline transporter gene SLC5A7) and matched controls completed self-report measure...

  11. Very boosted Higgs in gluon fusion

    International Nuclear Information System (INIS)

    The Higgs production and decay rates offer a new way to probe new physics beyond the Standard Model. While dynamics aiming at alleviating the hierarchy problem generically predict deviations in the Higgs rates, the current experimental analyses cannot resolve the long- and short-distance contributions to the gluon fusion process and thus cannot access directly the coupling between the Higgs and the top quark. We investigate the production of a boosted Higgs in association with a high-transverse momentum jet as an alternative to the t anti th channel to pin down this crucial coupling. Presented rst in the context of an effective field theory, our analysis is then applied to models of partial compositeness at the TeV scale and of natural supersymmetry.

  12. Boosted W/Z Tagging at ATLAS

    CERN Document Server

    Dattagupta, Aparajita; The ATLAS collaboration

    2016-01-01

    A detailed study of the techniques for identifying boosted hadronically decaying W or Z bosons is presented. The best performing algorithm for reconstructing, grooming and tagging bosonic jets as seen in studies using 8 TeV data and simulation is validated for W bosons with a wide range of transverse momenta using 13 TeV data and MC simulations. The same is studied for Z bosons in 13 TeV MC simulation. Improvement in tagger performance using detector tracking information is also studied. In addition, given that a hadronic jet has been identified as resulting from the hadronic decay of a W or Z, a technique is developed to discriminate between W and Z bosons using 8 TeV data. The alternative of using variable-R jets for capturing the hadronic decay products compared to standard techniques is also discussed.

  13. Boosting jet power in black hole spacetimes

    CERN Document Server

    Neilsen, David; Palenzuela, Carlos; Hirschmann, Eric W; Liebling, Steven L; Motl, Patrick M; Garret, T

    2010-01-01

    The extraction of rotational energy from a spinning black hole via the Blandford-Znajek mechanism has long been understood as an important component in models to explain energetic jets from compact astrophysical sources. Here we show more generally that the kinetic energy of the black hole, both rotational and translational, can be tapped, thereby producing even more luminous jets powered by the interaction of the black hole with its surrounding plasma. We study the resulting Poynting jet that arises from single boosted black holes and binary black hole systems. In the latter case, we find that increasing the orbital angular momenta of the system and/or the spins of the individual black holes results in an enhanced Poynting flux.

  14. Boosting jet power in black hole spacetimes

    Science.gov (United States)

    Neilsen, David; Lehner, Luis; Palenzuela, Carlos; Hirschmann, Eric W.; Liebling, Steven L.; Motl, Patrick M.; Garrett, Travis

    2011-01-01

    The extraction of rotational energy from a spinning black hole via the Blandford–Znajek mechanism has long been understood as an important component in models to explain energetic jets from compact astrophysical sources. Here we show more generally that the kinetic energy of the black hole, both rotational and translational, can be tapped, thereby producing even more luminous jets powered by the interaction of the black hole with its surrounding plasma. We study the resulting Poynting jet that arises from single boosted black holes and binary black hole systems. In the latter case, we find that increasing the orbital angular momenta of the system and/or the spins of the individual black holes results in an enhanced Poynting flux. PMID:21768341

  15. Giving top quark effective operators a boost

    CERN Document Server

    Englert, Christoph; Moore, Liam; Russell, Michael

    2016-01-01

    We investigate the prospects to systematically improve generic effective field theory-based searches for new physics in the top sector during LHC run 2 as well as the high luminosity phase. In particular, we assess the benefits of high momentum transfer final states on top EFT-fit as a function of systematic uncertainties in comparison with sensitivity expected from fully-resolved analyses focusing on $t\\bar t$ production. We find that constraints are typically driven by fully-resolved selections, while boosted top quarks can serve to break degeneracies in the global fit. This demystifies and clarifies the importance of high momentum transfer final states for global fits to new interactions in the top sector from direct measurements.

  16. Boosted top quarks and jet structure

    Energy Technology Data Exchange (ETDEWEB)

    Schaetzel, Sebastian [Ruprecht-Karls-Universitaet Heidelberg, Physikalisches Institut, Heidelberg (Germany)

    2015-09-15

    The Large Hadron Collider is the first particle accelerator that provides high enough energy to produce large numbers of boosted top quarks. The decay products of these top quarks are confined to a cone in the top quark flight direction and can be clustered into a single jet. Top quark reconstruction then amounts to analysing the structure of the jet and looking for subjets that are kinematically compatible with top quark decay. Many techniques have been developed in this context to identify top quarks in a large background of non-top jets. This article reviews the results obtained using data recorded in the years 2010-2012 by the experiments ATLAS and CMS. Studies of Standard Model top quark production and searches for new massive particles that decay to top quarks are presented. (orig.)

  17. Very boosted Higgs in gluon fusion

    Energy Technology Data Exchange (ETDEWEB)

    Grojean, C. [Univ. Autonoma de Barcelona, Bellaterra (Spain). ICREA at IFAE; Salvioni, E. [California Univ., Davis, CA (United States). Dept. of Physics; European Organization for Nuclear Research (CERN), Geneva (Switzerland); Padova Univ. (Italy). Dipt. di Fisica e Astronomica; INFN, Sezione di Padova (Italy); Schlaffer, M. [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany); Weiler, A. [European Organization for Nuclear Research (CERN), Geneva (Switzerland); Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany)

    2013-12-15

    The Higgs production and decay rates offer a new way to probe new physics beyond the Standard Model. While dynamics aiming at alleviating the hierarchy problem generically predict deviations in the Higgs rates, the current experimental analyses cannot resolve the long- and short-distance contributions to the gluon fusion process and thus cannot access directly the coupling between the Higgs and the top quark. We investigate the production of a boosted Higgs in association with a high-transverse momentum jet as an alternative to the t anti th channel to pin down this crucial coupling. Presented rst in the context of an effective field theory, our analysis is then applied to models of partial compositeness at the TeV scale and of natural supersymmetry.

  18. Boosted top quarks and jet structure

    International Nuclear Information System (INIS)

    The Large Hadron Collider is the first particle accelerator that provides high enough energy to produce large numbers of boosted top quarks. The decay products of these top quarks are confined to a cone in the top quark flight direction and can be clustered into a single jet. Top quark reconstruction then amounts to analysing the structure of the jet and looking for subjets that are kinematically compatible with top quark decay. Many techniques have been developed in this context to identify top quarks in a large background of non-top jets. This article reviews the results obtained using data recorded in the years 2010-2012 by the experiments ATLAS and CMS. Studies of Standard Model top quark production and searches for new massive particles that decay to top quarks are presented. (orig.)

  19. Opportunities to boost bioenergy in Lithuania

    Energy Technology Data Exchange (ETDEWEB)

    Silveira, Semida [International Secretariat, Swedish Energy Agency, Box 310, SE-631 04 Eskilstuna (Sweden); Andersson, Lars [Skogsvaardsstyrelsen Vaermland OErebro/Regional Forestry Board, Skogsenheten/Forest Department, P.O. Box 387, S-651 09 Karlstad (Sweden); Lebedys, Arvydas [Forest Economics Service, Forestry Department, Food and Agriculture Organization of UN, Viale delle Terme di Caracalla, 00100 Rome (Italy)

    2006-12-15

    Significant efforts have been made in Lithuania to enhance the utilization of bioenergy since the early 1990s. While opportunities are large and signs of development visible, bioenergy still needs technical, institutional and policy-related support for further development side by side with other industries. This paper discusses the existing bioenergy potential in Lithuanian forests, biofuels market formation in the region and possible roads to boost development. The retrofitting of heat plants, forest management and policies are reviewed as a way to identify opportunities to promote bioenergy in the country. It is shown that the interplay between national and regional forces can promote technological and managerial improvements in the forest industry while also enhancing the biomass supply and sustainability of bioenergy systems. (author) (author)

  20. Locally Boosted Graph Aggregation for Community Detection

    CERN Document Server

    Kun, Jeremy; Carter, Kevin

    2014-01-01

    Learning the right graph representation from noisy, multi-source data has garnered significant interest in recent years. A central tenet of this problem is relational learning. Here the objective is to incorporate the partial information each data source gives us in a way that captures the true underlying relationships. To address this challenge, we present a general, boosting-inspired framework for combining weak evidence of entity associations into a robust similarity metric. Building on previous work, we explore the extent to which different local quality measurements yield graph representations that are suitable for community detection. We present empirical results on a variety of datasets demonstrating the utility of this framework, especially with respect to real datasets where noise and scale present serious challenges. Finally, we prove a convergence theorem in an ideal setting and outline future research into other application domains.

  1. A boost to the French hydraulic plan

    International Nuclear Information System (INIS)

    A plan for boosting the hydroelectric power generation in France is presented, the first step of an energy policy based on the conclusions of the Grenelle Environnement Forum which targets a 23 percent objective for the renewable energies in France by 2020. Hydroelectricity represents nowadays 12 percent of total electric power generation. The plan is composed of three parts: attribution of concessions will be opened to competition (concessions of the 400 largest dams will be renewed); investments in dams will be strongly encouraged and assisted by the government in order to increase France's hydraulic power generation capacities and enhance its security of power supply - small and micro hydraulic power generation is to be developed; the quality of river waters will be improved

  2. Boosted top quarks and jet structure

    Science.gov (United States)

    Schätzel, Sebastian

    2015-09-01

    The Large Hadron Collider is the first particle accelerator that provides high enough energy to produce large numbers of boosted top quarks. The decay products of these top quarks are confined to a cone in the top quark flight direction and can be clustered into a single jet. Top quark reconstruction then amounts to analysing the structure of the jet and looking for subjets that are kinematically compatible with top quark decay. Many techniques have been developed in this context to identify top quarks in a large background of non-top jets. This article reviews the results obtained using data recorded in the years 2010-2012 by the experiments ATLAS and CMS. Studies of Standard Model top quark production and searches for new massive particles that decay to top quarks are presented.

  3. Boosting low-mass hadronic resonances

    CERN Document Server

    Shimmin, Chase

    2016-01-01

    Searches for new hadronic resonances typically focus on high-mass spectra, due to overwhelming QCD backgrounds and detector trigger rates. We present a study of searches for relatively low-mass hadronic resonances at the LHC in the case that the resonance is boosted by recoiling against a well-measured high-$p_{\\textrm{T}}$ probe such as a muon, photon or jet. The hadronic decay of the resonance is then reconstructed either as a single large-radius jet or as a resolved pair of standard narrow-radius jets, balanced in transverse momentum to the probe. We show that the existing 2015 LHC dataset of $pp$ collisions with $\\int\\mathcal{L}dt = 4\\ \\mathrm{fb}^{-1}$ should already have powerful sensitivity to a generic $Z'$ model which couples only to quarks, for $Z'$ masses ranging from 20-500 GeV/c$^2$.

  4. The attentional boost effect and context memory.

    Science.gov (United States)

    Mulligan, Neil W; Smith, S Adam; Spataro, Pietro

    2016-04-01

    Stimuli co-occurring with targets in a detection task are better remembered than stimuli co-occurring with distractors-the attentional boost effect (ABE). The ABE is of interest because it is an exception to the usual finding that divided attention during encoding impairs memory. The effect has been demonstrated in tests of item memory but it is unclear if context memory is likewise affected. Some accounts suggest enhanced perceptual encoding or associative binding, predicting an ABE on context memory, whereas other evidence suggests a more abstract, amodal basis of the effect. In Experiment 1, context memory was assessed in terms of an intramodal perceptual detail, the font and color of the study word. Experiment 2 examined context memory cross-modally, assessing memory for the modality (visual or auditory) of the study word. Experiments 3 and 4 assessed context memory with list discrimination, in which 2 study lists are presented and participants must later remember which list (if either) a test word came from. In all experiments, item (recognition) memory was also assessed and consistently displayed a robust ABE. In contrast, the attentional-boost manipulation did not enhance context memory, whether defined in terms of visual details, study modality, or list membership. There was some evidence that the mode of responding on the detection task (motoric response as opposed to covert counting of targets) may impact context memory but there was no evidence of an effect of target detection, per se. In sum, the ABE did not occur in context memory with verbal materials. (PsycINFO Database Record PMID:26348201

  5. Glucose starvation boosts Entamoeba histolytica virulence.

    Directory of Open Access Journals (Sweden)

    Ayala Tovy

    2011-08-01

    Full Text Available The unicellular parasite, Entamoeba histolytica, is exposed to numerous adverse conditions, such as nutrient deprivation, during its life cycle stages in the human host. In the present study, we examined whether the parasite virulence could be influenced by glucose starvation (GS. The migratory behaviour of the parasite and its capability to kill mammalian cells and to lyse erythrocytes is strongly enhanced following GS. In order to gain insights into the mechanism underlying the GS boosting effects on virulence, we analyzed differences in protein expression levels in control and glucose-starved trophozoites, by quantitative proteomic analysis. We observed that upstream regulatory element 3-binding protein (URE3-BP, a transcription factor that modulates E.histolytica virulence, and the lysine-rich protein 1 (KRiP1 which is induced during liver abscess development, are upregulated by GS. We also analyzed E. histolytica membrane fractions and noticed that the Gal/GalNAc lectin light subunit LgL1 is up-regulated by GS. Surprisingly, amoebapore A (Ap-A and cysteine proteinase A5 (CP-A5, two important E. histolytica virulence factors, were strongly down-regulated by GS. While the boosting effect of GS on E. histolytica virulence was conserved in strains silenced for Ap-A and CP-A5, it was lost in LgL1 and in KRiP1 down-regulated strains. These data emphasize the unexpected role of GS in the modulation of E.histolytica virulence and the involvement of KRiP1 and Lgl1 in this phenomenon.

  6. Loss of medial septum cholinergic neurons in THY-Tau22 mouse model: what links with tau pathology?

    Science.gov (United States)

    Belarbi, K; Burnouf, S; Fernandez-Gomez, F-J; Desmercières, J; Troquier, L; Brouillette, J; Tsambou, L; Grosjean, M-E; Caillierez, R; Demeyer, D; Hamdane, M; Schindowski, K; Blum, D; Buée, L

    2011-09-01

    Alzheimer's disease (AD) is a neurodegenerative disorder histologically defined by the cerebral accumulation of amyloid deposits and neurofibrillary tangles composed of hyperphosphorylated tau proteins. Loss of basal forebrain cholinergic neurons is another hallmark of the disease thought to contribute to the cognitive dysfunctions. To this date, the mechanisms underlying cholinergic neurons degeneration remain uncertain. The present study aimed to investigate the relationship between neurofibrillary degeneration and cholinergic defects in AD using THY-Tau22 transgenic mouse model exhibiting a major hippocampal AD-like tau pathology and hyperphosphorylated tau species in the septohippocampal pathway. Here, we report that at a time THY-Tau22 mice display strong reference memory alterations, the retrograde transport of fluorogold through the septohippocampal pathway is altered. This impairment is associated with a significant reduction in the number of choline acetyltransferase (ChAT)-immunopositive cholinergic neurons in the medial septum. Analysis of nerve growth factor (NGF) levels supports an accumulation of the mature neurotrophin in the hippocampus of THY-Tau22 mice, consistent with a decrease of its uptake or retrograde transport by cholinergic terminals. Finally, our data strongly support that tau pathology could be instrumental in the cholinergic neuronal loss observed in AD. PMID:21605043

  7. The distribution and morphological characteristics of cholinergic cells in the brain of monotremes as revealed by ChAT immunohistochemistry.

    Science.gov (United States)

    Manger, P R; Fahringer, H M; Pettigrew, J D; Siegel, J M

    2002-01-01

    The present study employs choline acetyltransferase (ChAT) immunohistochemistry to identify the cholinergic neuronal population in the central nervous system of the monotremes. Two of the three extant species of monotreme were studied: the platypus (Ornithorhynchus anatinus) and the short-beaked echidna (Tachyglossus aculeatus). The distribution of cholinergic cells in the brain of these two species was virtually identical. Distinct groups of cholinergic cells were observed in the striatum, basal forebrain, habenula, pontomesencephalon, cranial nerve motor nuclei, and spinal cord. In contrast to other tetrapods studied with this technique, we failed to find evidence for cholinergic cells in the hypothalamus, the parabigeminal nucleus (or nucleus isthmus), or the cerebral cortex. The lack of hypothalamic cholinergic neurons creates a hiatus in the continuous antero-posterior aggregation of cholinergic neurons seen in other tetrapods. This hiatus might be functionally related to the phenomenology of monotreme sleep and to the ontogeny of sleep in mammals, as juvenile placental mammals exhibit a similar combination of sleep elements to that found in adult monotremes. PMID:12476054

  8. Effects of chronic exposure to benzalkonium chloride in Oncorhynchus mykiss: cholinergic neurotoxicity, oxidative stress, peroxidative damage and genotoxicity.

    Science.gov (United States)

    Antunes, S C; Nunes, B; Rodrigues, S; Nunes, R; Fernandes, J; Correia, A T

    2016-07-01

    Benzalkonium chloride (BAC) is one of the most used conservatives in pharmaceutical preparations. However, its use is limited to a small set of external use formulations, due to its high toxicity. Benzalkonium chloride effects are related to the potential exertion of deleterious effects, mediated via oxidative stress and through interaction with membrane enzymes, leading to cellular damage. To address the ecotoxicity of this specific compound rainbow trouts were chronically exposed to BAC at environmental relevant concentrations (ranging from 0.100 to 1.050mg/L), and the biological response of cholinergic neurotoxicity, modulation of the antioxidant defense, phase II metabolism, lipid peroxidation and genotoxicity was studied. The obtained results showed a dual pattern of antioxidant response, with significant alterations in catalase activity (starting at 0.180mg/L), and lipid peroxidation, for intermediate (0.180 and 0.324mg/L) concentrations. No significant alterations occurred for glutathione-S-transferases activity. An unexpected increased of the acetylcholinesterase activity was also recorded for the individuals exposed to higher concentrations of BAC (starting at 0.180mg/L). Furthermore, exposure to BAC resulted in the establishment of genotoxic alterations, observable (for the specific case of the comet assay results) for all tested BAC concentrations. However, and considering that the oxidative response was not devisable, other mechanisms may be involved in the genotoxic effects reported here. PMID:27280532

  9. Augmentation of cholinergic-mediated amylase release by forskolin in mouse parotid gland

    International Nuclear Information System (INIS)

    Cholinergic-mediated amylase release in mouse parotid acini was augmented by forskolin; the potency but not the maximal response to carbachol was altered. Amylase released by carbachol plus forskolin was dependent on extracellular calcium and was mimicked by the calcium ionophore, A23187 plus forskolin. Forskolin was also shown to enhance carbachol-stimulated 45Ca2+ uptake into isolated acini. Hydroxylamine, nitroprusside, and 8-bromo-c-GMP each in combination with forskolin mimicked the effects of carbachol plus forskolin on amylase release. In the presence of carbachol (10-8M) forskolin did not augment c-AMP levels. However, in the presence of carbachol (5 x 10-7 M) or hydroxylamine (50 μM) forskolin did significantly augment c-AMP accumulation. These results suggest that calcium and c-GMP may mediate the augmentation of cholinergic-mediated amylase release by effects on c-AMP metabolism. 21 references, 1 figure, 3 tables

  10. Uranium chronic contamination effects on the cholinergic system: in vivo and in vitro approaches

    International Nuclear Information System (INIS)

    Uranium (U) is a heavy metal which occurs naturally in the environment. It is both a chemical and a radiological toxicant. The aim of this work was: (i) to assess the effects of U chronic exposure on the cholinergic system (biosynthesis and breakdown enzymes, receptors and on behaviour of adult, young or predisposed to neuro-degenerative illness (ApoE KO) rodents; (ii) to grasp the neurotoxic effects of U on human neuronal cells. In vivo, this work shows a structure- (cortex more sensitive than hippocampus), rodent model- (young more sensitive than adults), time- (sub-chronic exposure more harmful than chronic exposure), exposure level- and isotope-dependent effect of U. In vitro, the study underlined the neuro-cytotoxic U potential and the presence of uranium precipitates in cells. These results show the deleterious impact of U on neuronal cells, and demonstrate that U induces impairments on the cholinergic system and the behaviour of rodents. (author)

  11. Acetylcholine as a neuromodulator: cholinergic signaling shapes nervous system function and behavior

    OpenAIRE

    Picciotto, Marina R.; Higley, Michael J.; Mineur, Yann S.

    2012-01-01

    Acetylcholine in the brain alters neuronal excitability, influences synaptic transmission, induces synaptic plasticity and coordinates the firing of groups of neurons. As a result, it changes the state of neuronal networks throughout the brain and modifies their response to internal and external inputs: the classical role of a neuromodulator. Here we identify actions of cholinergic signaling on cellular and synaptic properties of neurons in several brain areas and discuss the consequences of ...

  12. Carbachol can be released at a cholinergic ganglionic synapse as a false transmitter.

    OpenAIRE

    Baux, G; Tauc, L

    1983-01-01

    Carbachol was injected into a presynaptic cholinergic neuron in the buccal ganglion of Aplysia and the quantal aspects of the Cl- -dependent postsynaptic response to a prolonged stimulation were analyzed by a statistical fluctuation method. The calculated amplitude of the miniature postsynaptic current was increased with respect to control. Statistical fluctuation analysis was also used to analyze the postsynaptic response obtained during ionophoretic application of acetylcholine and carbacho...

  13. Presynaptic transmitter content controls the number of quanta released at a neuro-neuronal cholinergic synapse.

    OpenAIRE

    Poulain, B; Baux, G; Tauc, L

    1986-01-01

    In the buccal ganglion of Aplysia the overloading of the cholinergic presynaptic neuron by exogenous acetylcholine (AcCho) led to an enhancement of the postsynaptic response. The deprivation of choline in the presynaptic neuron by extra- and/or intracellularly applied choline oxidase to prevent AcCho synthesis resulted in a decrease of the postsynaptic response. In both cases, the size of the calculated miniature postsynaptic current (i.e., the size of the quantum) remained unchanged. It was ...

  14. Attention, prediction and sequence learning : roles of the cholinergic basal forebrain and the retrosplenial cortex

    OpenAIRE

    Córdova, Christopher Andy

    2005-01-01

    Our ability to foresee and shape biologically important events relies on a combination of visuospatial attention, memory capacities, and an ability to learn new sequences of goal-directed action. A novel set of behavioral studies were conducted to investigate neurobiological processes that underlie selective attention and visuospatial sequence learning. The first experiment assessed a theorized computational role of basal forebrain cholinergic neurons in modulating attention by increasing sti...

  15. Disruption of cholinergic neurotransmission exacerbates Aβ-related cognitive impairment in preclinical Alzheimer's disease.

    Science.gov (United States)

    Lim, Yen Ying; Maruff, Paul; Schindler, Rachel; Ott, Brian R; Salloway, Stephen; Yoo, Don C; Noto, Richard B; Santos, Cláudia Y; Snyder, Peter J

    2015-10-01

    Disruption in cholinergic neurotransmission is one of the earliest neuropathological changes in preclinical Alzheimer's disease (AD) and may be associated with abnormal beta-amyloid (Aβ) accumulation. Therefore, disruption of cholinergic neurotransmission with scopolamine may unmask otherwise undetectable cognitive deficits in preclinical AD. To compare the effects of low-dose (0.20 mg s.c.) scopolamine on cognition between Aβ+ and Aβ- cognitively normal (CN) older adults using the Groton Maze Learning Test (GMLT). CN older adults completed the GMLT predose and then received scopolamine (0.20 mg) subcutaneously. Participants were reassessed 1-, 3-, 5-, 7-, and 8-hours post dose. All participants underwent positron emission tomography neuroimaging for Aβ using (18)F-florbetapir within 6 weeks of their baseline visit. Rhode Island Hospital Clinical Research Center, Providence, USA. CN older adults (n = 63), with a family history of AD and subjective memory complaints were enrolled (15 were classified as Aβ+ and 48 were classified as Aβ-). Cognition was assessed using the computerized GMLT at all predose and post-dose time points. At 5-hours post dose, the Aβ+ group performed significantly worse than the Aβ- group on all measures of learning efficiency and working memory and/or executive function (Cohen's d = 1.13-1.56). When participants were classified as having an abnormal response to scopolamine (based on change score at 5-hours post dose >0), 100% were correctly classified as Aβ+ and 67% as Aβ-. The results of this study suggest that diminished cholinergic tone likely occurs in preclinical AD, and as such, the use of a cholinergic stress test to perturb an already compromised neurotransmitter system may be an effective way of identifying CN older adults who are in this preclinical stage of AD. PMID:26233262

  16. Neuro-immune interactions via the cholinergic anti-inflammatory pathway

    OpenAIRE

    Gallowitsch-Puerta, Margot; Pavlov, Valentin A.

    2007-01-01

    The overproduction of TNF and other cytokines can cause the pathophysiology of numerous diseases. Controlling cytokine synthesis and release is critical for preventing unrestrained inflammation and maintaining health. Recent studies identified an efferent vagus nerve-based mechanism termed “the cholinergic anti-inflammatory pathway” that controls cytokine production and inflammation. Here we review current advances related to the role of this pathway in neuro-immune interactions that prevent ...

  17. Impairment of reward-related learning by cholinergic cell ablation in the striatum

    OpenAIRE

    Kitabatake, Yasuji; Hikida, Takatoshi; Watanabe, Dai; Pastan, Ira; Nakanishi, Shigetada

    2003-01-01

    The striatum in the basal ganglia-thalamocortical circuitry is a key neural substrate that is implicated in motor balance and procedural learning. The projection neurons in the striatum are dynamically modulated by nigrostriatal dopaminergic input and intrastriatal cholinergic input. The role of intrastriatal acetylcholine (ACh) in learning behaviors, however, remains to be fully clarified. In this investigation, we examine the involvement of intrastriatal ACh in different categories of...

  18. Nerve growth factor protects cholinergic neurons against quinolinic acid-induced excitotoxicity in wistar rats

    OpenAIRE

    Vasiljević Ivana D.; Jovanović Marina D.; Čolić Miodrag J.; Mićić D.; Ninković Milica; Maličević Živorad

    2004-01-01

    The etiology of neuronal death in neurodegenerative diseases, including Huntington's disease (HD) is still unknown. There could be a complex interplay between altered energy metabolism, excitotoxicity and oxidative stress. Excitotoxic striatal lesions induced by quinolinic acid (QA), were used to test for the neuroprotective actions of nerve growth factor (NGF) on striatal cholinergic and GABAergic neurons. QA is an endogenous excitotoxin acting on N-methyl-D-aspartate (NMDA) rec...

  19. Muscarinic cholinergic receptor (M2) plays a crucial role in the development of myopia in mice

    OpenAIRE

    Barathi, Veluchamy A.; Kwan, Jia Lin; Tan, Queenie S. W.; Weon, Sung Rhan; Seet, Li Fong; Goh, Liang Kee; Vithana, Eranga N.; Beuerman, Roger W.

    2013-01-01

    SUMMARY Myopia is a huge public health problem worldwide, reaching the highest incidence in Asia. Identification of susceptible genes is crucial for understanding the biological basis of myopia. In this paper, we have identified and characterized a functional myopia-associated gene using a specific mouse-knockout model. Mice lacking the muscarinic cholinergic receptor gene (M2 ; also known as Chrm2) were less susceptible to lens-induced myopia compared with wild-type mice, which showed signif...

  20. Muscarinic cholinergic receptor (M2) plays a crucial role in the development of myopia in mice

    OpenAIRE

    Barathi, Veluchamy A.; Jia Lin Kwan; Tan, Queenie S. W.; Sung Rhan Weon; Li Fong Seet; Liang Kee Goh; Vithana, Eranga N.; Beuerman, Roger W.

    2013-01-01

    SUMMARY Myopia is a huge public health problem worldwide, reaching the highest incidence in Asia. Identification of susceptible genes is crucial for understanding the biological basis of myopia. In this paper, we have identified and characterized a functional myopia-associated gene using a specific mouse-knockout model. Mice lacking the muscarinic cholinergic receptor gene (M2; also known as Chrm2) were less susceptible to lens-induced myopia compared with wild-type mice, which showed sign...

  1. Cholinergic degeneration and memory loss delayed by vitamin E in a Down syndrome mouse model

    OpenAIRE

    Lockrow, Jason; Prakasam, Annamalai; Huang, Peng; Bimonte-Nelson, Heather; Sambamurti, Kumar; Granholm, Ann-Charlotte

    2008-01-01

    Down syndrome (DS) individuals develop several neuropathological hallmarks seen in Alzheimer's disease, including cognitive decline and the early loss of cholinergic markers in the basal forebrain. These deficits are replicated in the Ts65Dn mouse, which contains a partial trisomy of murine chromosome 16, the orthologous genetic segment to human chromosome 21. Oxidative stress levels are elevated early in DS, and may contribute to the neurodegeneration seen in these individuals. We evaluated ...

  2. Cholinergic Dysfunction in Fragile X Syndrome and Potential Intervention: A Preliminary 1H MRS Study

    OpenAIRE

    Kesler, Shelli R.; Lightbody, Amy A.; Reiss, Allan L.

    2009-01-01

    Males with fragile X syndrome are at risk for significant cognitive and behavioral deficits, particularly those involving executive prefrontal systems. Disruption of the cholinergic system secondary to fragile X mental retardation protein deficiency may contribute to the cognitive-behavioral impairments associated with fragile X. We measured choline in the dorsolateral prefrontal cortex of 9 males with fragile X syndrome and 9 age-matched typically developing controls using 1H magnetic resona...

  3. Striatal Cholinergic Interneurons Control Motor Behavior and Basal Ganglia Function in Experimental Parkinsonism

    OpenAIRE

    Nicolas Maurice; Martine Liberge; Florence Jaouen; Samira Ztaou; Marwa Hanini; Jeremy Camon; Karl Deisseroth; Marianne Amalric; Lydia Kerkerian-Le Goff; Corinne Beurrier

    2015-01-01

    Despite evidence showing that anticholinergic drugs are of clinical relevance in Parkinson’s disease (PD), the causal role of striatal cholinergic interneurons (CINs) in PD pathophysiology remains elusive. Here, we show that optogenetic inhibition of CINs alleviates motor deficits in PD mouse models, providing direct demonstration for their implication in parkinsonian motor dysfunctions. As neural correlates, CIN inhibition in parkinsonian mice differentially impacts the excitability of stria...

  4. Novel information on the non-neuronal cholinergic system in orthopedics provides new possible treatment strategies for inflammatory and degenerative diseases

    Directory of Open Access Journals (Sweden)

    Sture Forsgren

    2009-07-01

    Full Text Available Anti-cholinergic agents are used in the treatment of several pathological conditions. Therapy regimens aimed at up-regulating cholinergic functions, such as treatment with acetylcholinesterase inhibitors, are also currently prescribed. It is now known that not only is there a neuronal cholinergic system but also a non-neuronal cholinergic system in various parts of the body. Therefore, interference with the effects of acetylcholine (ACh brought about by the local production and release of ACh should also be considered. Locally produced ACh may have proliferative, angiogenic, wound-healing, and immunomodulatory functions. Interestingly, cholinergic stimulation may lead to anti-inflammatory effects. Within this review, new findings for the locomotor system of a more widespread non-neuronal cholinergic system than previously expected will be discussed in relation to possible new treatment strategies. The conditions discussed are painful and degenerative tendon disease (tendinopathy/tendinosis, rheumatoid arthritis, and osteoarthritis.

  5. Lesions of cholinergic pedunculopontine tegmental nucleus neurons fail to affect cocaine or heroin self-administration or conditioned place preference in rats.

    Directory of Open Access Journals (Sweden)

    Stephan Steidl

    Full Text Available Cholinergic input to the ventral tegmental area (VTA is known to contribute to reward. Although it is known that the pedunculopontine tegmental nucleus (PPTg provides an important source of excitatory input to the dopamine system, the specific role of PPTg cholinergic input to the VTA in cocaine reward has not been previously determined. We used a diphtheria toxin conjugated to urotensin-II (Dtx::UII, the endogenous ligand for urotensin-II receptors expressed by PPTg cholinergic but not glutamatergic or GABAergic cells, to lesion cholinergic PPTg neurons. Dtx::UII toxin infusion resulted in the loss of 95.78 (±0.65% of PPTg cholinergic cells but did not significantly alter either cocaine or heroin self-administration or the development of cocaine or heroin conditioned place preferences. Thus, cholinergic cells originating in PPTg do not appear to be critical for the rewarding effects of cocaine or of heroin.

  6. A New Zero Voltage Switching Buck-Boost Type DC-DC Converter

    Directory of Open Access Journals (Sweden)

    Majid Delshad

    2010-03-01

    Full Text Available In this paper, a new zero voltage switching isolated buck-boost DC-DC converter with active clamp circuit is proposed. The active clamp circuit in this converter not only absorbs voltage spikes across the main switch but also provides soft switching conditions for all switches. All switches are PWM controlled which simplifies the control implementation. One of the main advantages of this converter is the that it operating can operate at high power levels while soft switching conditions exist in both buck and boost modes of converter operation. Since this converter can operate over a wide input voltage range, it can be employed in power factor correction. The experimental results obtained from a 150W prototype circuit operating at 100KHz are presented to confirm the integrity of the proposed circuit.

  7. ORAL ADMINISTRATION OF NUTMEG ON MEMORY BOOSTING AND REGAINING IN WISTAR ALBINO RATS

    Directory of Open Access Journals (Sweden)

    G Jissa

    2014-01-01

    Full Text Available Background: This study provides further evidence for improvement of memory by oral consumption of nutmeg. The present study was undertaken with an objective to study the effects of oral administration of nutmeg on memory boosting and regaining. Methods: Here we investigate the influence of oral intake of nutmeg on behavioral task performance by using T-maze and radial arm maze and physiological measures relative to a milk control group. Results: We have observed significant memory boosting and memory regaining effects of nutmeg when administered orally. This effect may be due to facilitation of acetylcholine activity by decreasing acetylcholinesterase activity of nutmeg. Hence we recommend further research in this area by investigating compound metabolism to optimize quantification of memory performance following nutmeg consumption.

  8. Prime-boost strategies in mucosal immunization affect local IgA production and the type of Th response

    Directory of Open Access Journals (Sweden)

    Fabio eFiorino

    2013-05-01

    Full Text Available Combinations of different delivery routes for priming and boosting represent vaccination strategies that can modulate magnitude, quality, and localization of the immune response. A murine model was used to study T cell clonal expansion following nasal or subcutaneous priming, and secondary immune responses after boosting by either homologous or heterologous routes. T cell primary activation was studied by using the adoptive transfer model of ovalbumin-specific transgenic CD4+ T cells. Both nasal and subcutaneous immunization efficiently elicited, in the respective draining lymph nodes, primary clonal expansion of antigen-specific CD4+ T cells that disseminated towards distal lymph nodes (mesenteric and iliac and the spleen. After boosting, a very high serum IgG response was induced in all groups independent of the combination of immunization routes used, while significant levels of local IgA were detected only in mice boosted by the nasal route. Mucosal priming drove a stronger Th1 polarization than the systemic route, as shown by serum IgG subclass analysis. IFN-gamma production was observed in splenocytes of all groups, while prime-boost vaccine combinations that included the mucosal route, yielded higher levels of IL-17. Memory lymphocytes were identified in both spleen and draining lymph nodes in all immunized mice, with the highest number of IL-2 producing cells detected in mice primed and boosted by the nasal route. This work shows the critical role of immunization routes in modulating quality and localization of immune responses, in prime-boost vaccine strategies.

  9. The role of ventral midline thalamus in cholinergic-based recovery in the amnestic rat.

    Science.gov (United States)

    Bobal, M G; Savage, L M

    2015-01-29

    The thalamus is a critical node for several pathways involved in learning and memory. Damage to the thalamus by trauma, disease or malnourishment can impact the effectiveness of the prefrontal cortex (PFC) and hippocampus (HPC) and lead to a profound amnesia state. Using the pyrithiamine-induced thiamine deficiency (PTD) rat model of human Wernicke-Korsakoff syndrome, we tested the hypothesis that co-infusion of the acetylcholinesterase inhibitor physostigmine across the PFC and HPC would recover spatial alternation performance in PTD rats. When cholinergic tone was increased by dual injections across the PFC-HPC, spontaneous alternation performance in PTD rats was recovered. In addition, we tested a second hypothesis that two ventral midline thalamic nuclei, the rhomboid nucleus and nucleus reuniens (Rh-Re), form a critical node needed for the recovery of function observed when cholinergic tone was increased across the PFC and HPC. By using the GABAA agonist muscimol to temporarily deactivate the Rh-Re the recovery of alternation behavior obtained in the PTD model by cholinergic stimulation across the PFC-HPC was blocked. In control pair-fed (PF) rats, inactivation of the Rh-Re impaired spontaneous alternation. However, when inactivation of the Rh-Re co-occurred with physostigmine infusions across the PFC-HPC, PF rats had normal performance. These results further demonstrate that the Rh-Re is critical in facilitating interactions between the HPC and PFC, but other redundant pathways also exist. PMID:25446352

  10. [Bowel obstruction-induced cholinergic crisis with progressive respiratory failure following distigmine bromide treatment].

    Science.gov (United States)

    Kobayashi, Kazuki; Sekiguchi, Hiroshi; Sato, Nobuhiro; Hirose, Yasuo

    2016-03-01

    A 54-year-old female experienced rapid respiratory failure while being transported in an ambulance to our emergency department for evaluation and management of constipation and abdominal pain. The patient was on treatment with distigmine bromide for postoperative urination disorder and magnesium oxide for constipation. Increased salivary secretions, diminished respiratory excursion, type 2 respiratory failure (PaCO2 : 65 mmHg), low serum cholinesterase, and hypermagnesemia were detected. Imaging studies revealed that the patient had bilateral aspiration pneumonia, fecal impaction in the rectum, and a distended colon causing ileus. The patient was mechanically ventilated and was weaned off the ventilator on day 3. Therapeutic drug monitoring after discharge revealed that the serum level of distigmine bromide on admission was markedly elevated (377.8 ng/mL vs. the normal therapeutic level of 5-10 ng/mL). Distigmine bromide induced a cholinergic crisis with a resultant increase in airway secretions and respiratory failure. In this particular case, orally administered distigmine bromide was excessively absorbed because of prolonged intestinal transit time secondary to fecal impaction and sluggish bowel movement; this caused a cholinergic crisis and hypermagnesemia contributing to respiratory failure. Clinicians should be aware that bowel obstruction in a patient treated with distigmine bromide can increase the risk of a cholinergic crisis. PMID:27255021

  11. The effect of prenatal gamma irradiation on the cholinergic enzymes of the brain in the 30-day-old squirrel monkey

    International Nuclear Information System (INIS)

    The effect of prenatal 60Co irradiation (10 and 100 rad) on the activity of the enzymes choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) in brains of 30-day-old squirrel monkeys was investigated. In the 100 rad group, there was a statistically significant increase in both enzyme activities in the visual and somatosensory cortex, the hippocampus and the caudate; a similar trend was observed in the motor, auditory and frontal cortical areas, the cerebellum and the thalamus. ChAT activity increased 32% more in the hippocampus and 23% more in the caudate than did AChE. Thus the ratio of degradation to synthesis of acetylcholine decreased significantly in these two areas. The 10-rad group showed no significant differences from the controls in any of the brain areas tested but this does not exclude the possibility that low dose effects on cholinergic enzymes may be apparent in a younger foetus. (U.K.)

  12. Oral Administration of Gintonin Attenuates Cholinergic Impairments by Scopolamine, Amyloid-β Protein, and Mouse Model of Alzheimer’s Disease

    OpenAIRE

    Kim, Hyeon-Joong; Shin, Eun-Joo; Lee, Byung-Hwan; Choi, Sun-Hye; Jung, Seok-Won; Cho, Ik-Hyun; Hwang, Sung-Hee; Kim, Joon Yong; Han, Jung-Soo; Chung, ChiHye; Jang, Choon-Gon; Rhim, Hyewon; Kim, Hyoung-Chun; Nah, Seung-Yeol

    2015-01-01

    Gintonin is a novel ginseng-derived lysophosphatidic acid (LPA) receptor ligand. Oral administration of gintonin ameliorates learning and memory dysfunctions in Alzheimer’s disease (AD) animal models. The brain cholinergic system plays a key role in cognitive functions. The brains of AD patients show a reduction in acetylcholine concentration caused by cholinergic system impairments. However, little is known about the role of LPA in the cholinergic system. In this study, we used gintonin to i...

  13. Buck-Boost/Forward Hybrid Converter for PV Energy Conversion Applications

    OpenAIRE

    Sheng-Yu Tseng; Chien-Chih Chen; Hung-Yuan Wang

    2014-01-01

    This paper presents a charger and LED lighting (discharger) hybrid system with a PV array as its power source for electronic sign indicator applications. The charger adopts buck-boost converter which is operated in constant current mode to charge lead-acid battery and with the perturb and observe method to extract maximum power of PV arrays. Their control algorithms are implemented by microcontroller. Moreover, forward converter with active clamp circuit is operated in voltage regulation cond...

  14. Photovoltaic Simplified Boost Z Source Inverter for Ac Module Applications

    Directory of Open Access Journals (Sweden)

    J. Sam Alaric

    2014-08-01

    Full Text Available This study mainly proposed PV z source boost inverter used to boundary grid or ac module applications. Separate types of converter used for solar system due to its current lagging, here capacitor multiplier based boost converter introduced for maintain the current lagging and voltage gain. Here, the switched inductor z source inverter implemented for grid interface. Proposed z source inverter is controlled by pulse width modulation. A simplified capacitor multiplier controlled by continuous conduction mode, A detailed topology analysis and a generalized discussion are given. The multiplier boost converter has the merits of maintain voltage level and reducing cost and current lagging. Simulation results are implemented and analysis MATLAB software.

  15. Boosted Black Holes on Kaluza-Klein Bubbles

    CERN Document Server

    Iguchi, Hideo; Tomizawa, Shinya

    2007-01-01

    We construct an exact stationary solution of black hole -- bubble sequence in the five dimensional Kaluza-Klein theory by using solitonic solution generating techniques. The solution describes two boosted black holes with topology S^3 on a Kaluza-Klein bubble and has a linear momentum component in the compactified direction. The ADM mass and the linear momentum depend on the two boosted velocity parameters of black holes. In the effective four dimensional theory, the solution has an electric charge which is proportional to the linear momentum. The solution includes the static solution found by Elvang and Horowitz and a limit of single boosted black string.

  16. Remote Sensing Data Binary Classification Using Boosting with Simple Classifiers

    Directory of Open Access Journals (Sweden)

    Nowakowski Artur

    2015-10-01

    Full Text Available Boosting is a classification method which has been proven useful in non-satellite image processing while it is still new to satellite remote sensing. It is a meta-algorithm, which builds a strong classifier from many weak ones in iterative way. We adapt the AdaBoost.M1 boosting algorithm in a new land cover classification scenario based on utilization of very simple threshold classifiers employing spectral and contextual information. Thresholds for the classifiers are automatically calculated adaptively to data statistics.

  17. A boost for the ISOLDE beams

    CERN Multimedia

    Corinne Pralavorio

    2015-01-01

    The first HIE-ISOLDE cryomodule was commissioned at the end of October. The radioactive ion beams can now be accelerated to 4.3 MeV per nucleon.   The ISOLDE beamline that supplies the Miniball array. The first HIE-ISOLDE cryomodule can be seen in the background, in its light-grey cryostat. ISOLDE is getting an energy boost. The first cryomodule of the new superconducting linear accelerator HIE-ISOLDE (High Intensity and Energy ISOLDE), located downstream of the REX-ISOLDE accelerator, increases the energy of the radioactive ion beams from 3 to 4.3 MeV per nucleon. It supplies the Miniball array, where an experiment using radioactive zinc ions (see box) began at the end of October. This is the first stage in the commissioning of HIE-ISOLDE. The facility will ultimately be equipped with four cryomodules that will accelerate the beams to 10 MeV per nucleon. Each cryomodule has five accelerating cavities and a solenoid, which focuses the beam. All of these components are superconducting. This first ...

  18. Exploiting tRNAs to Boost Virulence

    Directory of Open Access Journals (Sweden)

    Suki Albers

    2016-01-01

    Full Text Available Transfer RNAs (tRNAs are powerful small RNA entities that are used to translate nucleotide language of genes into the amino acid language of proteins. Their near-uniform length and tertiary structure as well as their high nucleotide similarity and post-transcriptional modifications have made it difficult to characterize individual species quantitatively. However, due to the central role of the tRNA pool in protein biosynthesis as well as newly emerging roles played by tRNAs, their quantitative assessment yields important information, particularly relevant for virus research. Viruses which depend on the host protein expression machinery have evolved various strategies to optimize tRNA usage—either by adapting to the host codon usage or encoding their own tRNAs. Additionally, several viruses bear tRNA-like elements (TLE in the 5′- and 3′-UTR of their mRNAs. There are different hypotheses concerning the manner in which such structures boost viral protein expression. Furthermore, retroviruses use special tRNAs for packaging and initiating reverse transcription of their genetic material. Since there is a strong specificity of different viruses towards certain tRNAs, different strategies for recruitment are employed. Interestingly, modifications on tRNAs strongly impact their functionality in viruses. Here, we review those intersection points between virus and tRNA research and describe methods for assessing the tRNA pool in terms of concentration, aminoacylation and modification.

  19. New ways to boost molecular dynamics simulations.

    Science.gov (United States)

    Krieger, Elmar; Vriend, Gert

    2015-05-15

    We describe a set of algorithms that allow to simulate dihydrofolate reductase (DHFR, a common benchmark) with the AMBER all-atom force field at 160 nanoseconds/day on a single Intel Core i7 5960X CPU (no graphics processing unit (GPU), 23,786 atoms, particle mesh Ewald (PME), 8.0 Å cutoff, correct atom masses, reproducible trajectory, CPU with 3.6 GHz, no turbo boost, 8 AVX registers). The new features include a mixed multiple time-step algorithm (reaching 5 fs), a tuned version of LINCS to constrain bond angles, the fusion of pair list creation and force calculation, pressure coupling with a "densostat," and exploitation of new CPU instruction sets like AVX2. The impact of Intel's new transactional memory, atomic instructions, and sloppy pair lists is also analyzed. The algorithms map well to GPUs and can automatically handle most Protein Data Bank (PDB) files including ligands. An implementation is available as part of the YASARA molecular modeling and simulation program from www.YASARA.org. PMID:25824339

  20. Industry poised to boost production on Angola/Cabinda acreage

    International Nuclear Information System (INIS)

    This paper reports that development spending off Angola will peak at $750 million/year in 1993 and 1994 as operators start to implement plans to boost oil to 680,000 b/d in 1996 from 505,000 b/d last year. And during the next 9 years, upstream spending will jump to $4.7 billion at 1992 prices, compared with $3.3 billion spent in the past 9 years, says County NatWest WoodMac. Angolan exploration and appraisal drilling this year will slip from the 1991 record level of 36 wells to about 33 wells. The decline will be eased by first wells drilled on newly awarded Blocks 4, 6, and 7 operated by units of Ranger Oil Ltd., Conoco Inc., and Ste. Nationale Elf Aquitaine. As exploration drops in more mature areas, activity will shift to frontier regions. As a result, drilling activity in the mid-1990s will be at least as high as the record levels of 1991, WoodMac predicts

  1. Melanoma Drug Boosting Survival for Many, Study Shows

    Science.gov (United States)

    ... nlm.nih.gov/medlineplus/news/fullstory_158928.html Melanoma Drug Boosting Survival for Many, Study Shows Keytruda ... 2016 (HealthDay News) -- A new drug for advanced melanoma is dramatically shifting the odds in favor of ...

  2. Severe Obesity May Boost Infection Risk After Heart Surgery

    Science.gov (United States)

    ... nih.gov/medlineplus/news/fullstory_159143.html Severe Obesity May Boost Infection Risk After Heart Surgery Excess ... new study suggests. The researchers found that severe obesity was linked to much higher odds of developing ...

  3. Zika's Delivery Via Mosquito Bite May Boost Its Effect

    Science.gov (United States)

    ... page: https://medlineplus.gov/news/fullstory_159484.html Zika's Delivery Via Mosquito Bite May Boost Its Effect ... The inflammation caused by a mosquito bite helps Zika and other viruses spread through the body more ...

  4. Omega-3 Fish Oil Supplements Might Boost Antidepressants' Effects

    Science.gov (United States)

    ... html Omega-3 Fish Oil Supplements Might Boost Antidepressants' Effects Data from 8 randomized clinical trials suggests ... fish oil supplements may improve the effectiveness of antidepressants, new research suggests. Researchers reviewed the findings of ...

  5. Remote Sensing Data Binary Classification Using Boosting with Simple Classifiers

    Science.gov (United States)

    Nowakowski, Artur

    2015-10-01

    Boosting is a classification method which has been proven useful in non-satellite image processing while it is still new to satellite remote sensing. It is a meta-algorithm, which builds a strong classifier from many weak ones in iterative way. We adapt the AdaBoost.M1 boosting algorithm in a new land cover classification scenario based on utilization of very simple threshold classifiers employing spectral and contextual information. Thresholds for the classifiers are automatically calculated adaptively to data statistics. The proposed method is employed for the exemplary problem of artificial area identification. Classification of IKONOS multispectral data results in short computational time and overall accuracy of 94.4% comparing to 94.0% obtained by using AdaBoost.M1 with trees and 93.8% achieved using Random Forest. The influence of a manipulation of the final threshold of the strong classifier on classification results is reported.

  6. Insurance Mandates Boost U.S. Autism Diagnoses

    Science.gov (United States)

    ... page: https://medlineplus.gov/news/fullstory_159812.html Insurance Mandates Boost U.S. Autism Diagnoses Early treatment provides ... the Penn researchers analyzed inpatient and outpatient health insurance claims from 2008 through 2012 for more than ...

  7. Superconducting Electric Boost Pump for Nuclear Thermal Propulsion Project

    Data.gov (United States)

    National Aeronautics and Space Administration — A submersible, superconducting electric boost pump sized to meet the needs of future Nuclear Thermal Propulsion systems in the 25,000 lbf thrust range is proposed....

  8. Exposure / Ritual Prevention Therapy Boosts Antidepressant Treatment of OCD

    Science.gov (United States)

    ... NIMH (99 items) Exposure / Ritual Prevention Therapy Boosts Antidepressant Treatment of OCD CBT Trumps Antipsychotic for Augmentation, ... Update A form of behavioral therapy can augment antidepressant treatment of obsessive compulsive disorder (OCD) better than ...

  9. A Little Excess Weight May Boost Colon Cancer Survival

    Science.gov (United States)

    ... 158930.html A Little Excess Weight May Boost Colon Cancer Survival Researchers saw an effect, but experts stress ... a surprise, a new study found that overweight colon cancer patients tended to have better survival than their ...

  10. Severe Obesity May Boost Infection Risk After Heart Surgery

    Science.gov (United States)

    ... https://medlineplus.gov/news/fullstory_159143.html Severe Obesity May Boost Infection Risk After Heart Surgery Excess ... new study suggests. The researchers found that severe obesity was linked to much higher odds of developing ...

  11. Face Alignment using Boosted Appeareance Model (Discriminative Appearance Model)

    OpenAIRE

    Muddamsetty, Satya Mahesh

    2009-01-01

    This thesis explores decriminative face alignment using Boosted Appearance Model (BAM). In this method face alignment is done by maximizing the score of the trained two classifier which learns both correct and incorrect alignment and is able to distinguish correct and incorrect alignment so that the correct alignment gets maximum positve score. During the training stage we trained Point Distribution Model (PDM) which acts as shape model and a boosting based classifier based on Haar like Recta...

  12. Positive Semidefinite Metric Learning Using Boosting-like Algorithms

    OpenAIRE

    Shen, Chunhua; Kim, Junae; Wang, Lei; Hengel, Anton van den

    2011-01-01

    The success of many machine learning and pattern recognition methods relies heavily upon the identification of an appropriate distance metric on the input data. It is often beneficial to learn such a metric from the input training data, instead of using a default one such as the Euclidean distance. In this work, we propose a boosting-based technique, termed BoostMetric, for learning a quadratic Mahalanobis distance metric. Learning a valid Mahalanobis distance metric requires enforcing the co...

  13. Complexified boost invariance and holographic heavy ion collisions

    OpenAIRE

    Gubser, Steven; van der Schee, Wilke

    2014-01-01

    At strong coupling holographic studies have shown that heavy ion collisions do not obey normal boost invariance. Here we study a modified boost invariance through a complex shift in time, and show that this leads to surprisingly good agreement with numerical holographic computations. When including perturbations the agreement becomes even better, both in the hydrodynamic and the far-from-equilibrium regime. One of the main advantages is an analytic formulation of the stress-energy tensor of t...

  14. Boosted dark matter signals uplifted with self-interaction

    OpenAIRE

    Kyoungchul Kong; Gopolang Mohlabeng; Jong-Chul Park

    2014-01-01

    We explore detection prospects of a non-standard dark sector in the context of boosted dark matter. We focus on a scenario with two dark matter particles of a large mass difference, where the heavier candidate is secluded and interacts with the standard model particles only at loops, escaping existing direct and indirect detection bounds. Yet its pair annihilation in the galactic center or in the Sun may produce boosted stable particles, which could be detected as visible Cherenkov light in l...

  15. Boost IORT in Breast Cancer: Body of Evidence

    OpenAIRE

    Felix Sedlmayer; Roland Reitsamer; Christoph Fussl; Ingrid Ziegler; Franz Zehentmayr; Heinz Deutschmann; Peter Kopp; Gerd Fastner

    2014-01-01

    The term IORT (intraoperative radiotherapy) is currently used for various techniques that show decisive differences in dose delivery. The largest evidence for boost IORT preceding whole breast irradiation (WBI) originates from intraoperative electron treatments with single doses around 10 Gy, providing outstandingly low local recurrence rates in any risk constellation also at long term analyses. Compared to other boost methods, an intraoperative treatment has evident advantages as follows. Pr...

  16. Boosting the partial least square algorithm for regression modelling

    Institute of Scientific and Technical Information of China (English)

    Ling YU; Tiejun WU

    2006-01-01

    Boosting algorithms are a class of general methods used to improve the general performance of regression analysis. The main idea is to maintain a distribution over the train set. In order to use the given distribution directly,a modified PLS algorithm is proposed and used as the base learner to deal with the nonlinear multivariate regression problems. Experiments on gasoline octane number prediction demonstrate that boosting the modified PLS algorithm has better general performance over the PLS algorithm.

  17. Boosting-like Deep Learning For Pedestrian Detection

    OpenAIRE

    Wang, Lei; Zhang, Baochang

    2015-01-01

    This paper proposes boosting-like deep learning (BDL) framework for pedestrian detection. Due to overtraining on the limited training samples, overfitting is a major problem of deep learning. We incorporate a boosting-like technique into deep learning to weigh the training samples, and thus prevent overtraining in the iterative process. We theoretically give the details of derivation of our algorithm, and report the experimental results on open data sets showing that BDL achieves a better sta...

  18. Design of a high efficiency 30 kW boost composite converter

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hyeokjin [Univ. of Colorado, Boulder, CO (United States); Chen, Hua [Univ. of Colorado, Boulder, CO (United States); Maksimovic, Dragan [Univ. of Colorado, Boulder, CO (United States); Erickson, Robert W. [Univ. of Colorado, Boulder, CO (United States)

    2015-09-20

    An experimental 30 kW boost composite converter is described in this paper. The composite converter architecture, which consists of a buck module, a boost module, and a dual active bridge module that operates as a DC transformer (DCX), leads to substantial reductions in losses at partial power points, and to significant improvements in weighted efficiency in applications that require wide variations in power and conversion ratio. A comprehensive loss model is developed, accounting for semiconductor conduction and switching losses, capacitor losses, as well as dc and ac losses in magnetic components. Based on the developed loss model, the module and system designs are optimized to maximize efficiency at a 50% power point. Experimental results for the 30 kW prototype demonstrate 98.5%peak efficiency, very high efficiency over wide ranges of power and voltage conversion ratios, as well as excellent agreements between model predictions and measured efficiency curves.

  19. Libidibia ferrea Mature Seeds Promote Antinociceptive Effect by Peripheral and Central Pathway: Possible Involvement of Opioid and Cholinergic Receptors

    Directory of Open Access Journals (Sweden)

    Luis Armando Sawada

    2014-01-01

    Full Text Available Libidibia ferrea (LF is a medicinal plant that holds many pharmacological properties. We evaluated the antinociceptive effect in the LF aqueous seed extract and Lipidic Portion of Libidibia ferrea (LPLF, partially elucidating their mechanisms. Histochemical tests and Gas chromatography of the LPLF were performed to characterize its fatty acids. Acetic acid-induced abdominal constriction, formalin-induced pain, and hot-plate test in mice were employed in the study. In all experiments, aqueous extract or LPLF was administered systemically at the doses of 1, 5, and 10 mg/kg. LF aqueous seed extract and LPLF demonstrated a dose-dependent antinociceptive effect in all tests indicating both peripheral anti-inflammatory and central analgesia properties. Also, the use of atropine (5 mg/kg, naloxone (5 mg/kg in the abdominal writhing test was able to reverse the antinociceptive effect of the LPLF, indicating that at least one of LF lipids components is responsible for the dose related antinociceptive action in chemical and thermal models of nociception in mice. Together, the present results suggested that Libidibia ferrea induced antinociceptive activity is possibly related to its ability to inhibit opioid, cholinergic receptors, and cyclooxygenase-2 pathway, since its main component, linoleic acid, has been demonstrated to produce such effect in previous studies.

  20. Libidibia ferrea Mature Seeds Promote Antinociceptive Effect by Peripheral and Central Pathway: Possible Involvement of Opioid and Cholinergic Receptors

    Science.gov (United States)

    Sawada, Luis Armando; Monteiro, Vanessa Sâmia da Conçeição; Rabelo, Guilherme Rodrigues; Dias, Germana Bueno; Da Cunha, Maura; do Nascimento, José Luiz Martins; Bastos, Gilmara de Nazareth Tavares

    2014-01-01

    Libidibia ferrea (LF) is a medicinal plant that holds many pharmacological properties. We evaluated the antinociceptive effect in the LF aqueous seed extract and Lipidic Portion of Libidibia ferrea (LPLF), partially elucidating their mechanisms. Histochemical tests and Gas chromatography of the LPLF were performed to characterize its fatty acids. Acetic acid-induced abdominal constriction, formalin-induced pain, and hot-plate test in mice were employed in the study. In all experiments, aqueous extract or LPLF was administered systemically at the doses of 1, 5, and 10 mg/kg. LF aqueous seed extract and LPLF demonstrated a dose-dependent antinociceptive effect in all tests indicating both peripheral anti-inflammatory and central analgesia properties. Also, the use of atropine (5 mg/kg), naloxone (5 mg/kg) in the abdominal writhing test was able to reverse the antinociceptive effect of the LPLF, indicating that at least one of LF lipids components is responsible for the dose related antinociceptive action in chemical and thermal models of nociception in mice. Together, the present results suggested that Libidibia ferrea induced antinociceptive activity is possibly related to its ability to inhibit opioid, cholinergic receptors, and cyclooxygenase-2 pathway, since its main component, linoleic acid, has been demonstrated to produce such effect in previous studies. PMID:24860820

  1. The cholinergic antagonist gymnodimine improves Aβ and tau neuropathology in an in vitro model of Alzheimer disease.

    Science.gov (United States)

    Alonso, Eva; Vale, Carmen; Vieytes, Mercedes R; Laferla, Frank M; Giménez-Llort, Lydia; Botana, Luis M

    2011-01-01

    Gymnodimine (GYM) is a marine phycotoxin with a macrocyclic imine structure, isolated from extracts of the dinoflagellate Karenia selliformis known to act as a cholinergic antagonist with subtype selectivity. However, no data on the chronic effects of this compound has been reported so far. In this work, we evaluated the effect of long term exposure of cortical neurons to gymnodimine in the progress of Alzheimer disease (AD) pathology in vitro. Treatment of cortical neurons with 50 nM gymnodimine decreased the intracellular amyloid beta (Aβ) accumulation and the levels of the hyperphosphorylated isoforms of tau protein recognized by AT8 and AT100 antibodies. These results are suggested to be mediated by the increase in the inactive isoform of the glycogen synthase kinase-3 (phospho GSK-3 Ser9), the decrease in the levels of the active isoform of the ERK1/2 kinase and the increase in acetylcholine (Ach) synthesis elicited by long term exposure of cortical neurons to the toxin. Moreover, gymnodimine decreased glutamate-induced neurotoxicity in vitro. Altogether these results indicate that the marine phycotoxin gymnodimine may constitute a valuable tool for the development of drugs to treat neurodegenerative diseases. PMID:21691095

  2. Concomitant boost radiotherapy for muscle invasive bladder cancer

    International Nuclear Information System (INIS)

    Purpose: To evaluate the feasibility and efficacy of a concomitant partial bladder boost schedule in radiotherapy for invasive bladder cancer, coupling a limited boost volume with shortening of the overall treatment time. Methods and materials: Between 1994 and 1999, 50 patients with a T2-T4 N0M0 transitional cell carcinoma of the bladder received radiotherapy delivered in a short overall treatment time with a concomitant boost technique. With this technique a dose of 40 Gy in 2-Gy fractions was administered to the small pelvis with a concomitant boost limited to the bladder tumor area plus margin of 15 Gy in fractions of 0.75 Gy. The total tumor dose was 55 Gy in 20 fractions in 4 weeks. Toxicity was scored according to EORTC/RTOG toxicity criteria. Results: The feasibility of the treatment was good. Severe acute toxicity ≥G3 was observed in seven patients (14%). Severe late toxicity ≥G3 was observed in six patients (13%). Thirty-seven patients (74%) showed a complete and five (10 %) a partial remission after treatment. The actuarial 3-year freedom of local progression was 55%. Conclusion: In external radiotherapy for muscle invasive bladder cancer a concomitant boost technique coupling a partial bladder boost with shortening of the overall treatment time provides a high probability of local control with acceptable toxicity

  3. Nuclear organization of cholinergic, catecholaminergic, serotonergic and orexinergic systems in the brain of the Tasmanian devil (Sarcophilus harrisii).

    Science.gov (United States)

    Patzke, Nina; Bertelsen, Mads F; Fuxe, Kjell; Manger, Paul R

    2014-11-01

    This study investigated the nuclear organization of four immunohistochemically identifiable neural systems (cholinergic, catecholaminergic, serotonergic and orexinergic) within the brains of three male Tasmanian devils (Sarcophilus harrisii), which had a mean brain mass of 11.6g. We found that the nuclei generally observed for these systems in other mammalian brains were present in the brain of the Tasmanian devil. Despite this, specific differences in the nuclear organization of the cholinergic, catecholaminergic and serotonergic systems appear to carry a phylogenetic signal. In the cholinergic system, only the dorsal hypothalamic cholinergic nucleus could be observed, while an extra dorsal subdivision of the laterodorsal tegmental nucleus and cholinergic neurons within the gelatinous layer of the caudal spinal trigeminal nucleus were observed. Within the catecholaminergic system the A4 nucleus of the locus coeruleus complex was absent, as was the caudal ventrolateral serotonergic group of the serotonergic system. The organization of the orexinergic system was similar to that seen in many mammals previously studied. Overall, while showing strong similarities to the organization of these systems in other mammals, the specific differences observed in the Tasmanian devil reveal either order specific, or class specific, features of these systems. Further studies will reveal the extent of change in the nuclear organization of these systems in marsupials and how these potential changes may affect functionality. PMID:25150966

  4. Age-related changes in nicotine response of cholinergic and non-cholinergic laterodorsal tegmental neurons: implications for the heightened adolescent susceptibility to nicotine addiction

    DEFF Research Database (Denmark)

    Christensen, Mark Holm; Ishibashi, Masaru; Nielsen, Michael Linnemann;

    2014-01-01

    The younger an individual starts smoking, the greater the likelihood that addiction to nicotine will develop, suggesting that neurobiological responses vary across age to the addictive component of cigarettes. Cholinergic neurons of the laterodorsal tegmental nucleus (LDT) are importantly involved...... in the development of addiction, however, the effects of nicotine on LDT neuronal excitability across ontogeny are unknown. Nicotinic effects on LDT cells across different age groups were examined using calcium imaging and whole-cell patch clamping. Within the youngest age group (P7–P15), nicotine...... cells to target regions involved in development of addiction. Such output would be expected to be promotive of addiction; therefore, ontogenetic differences in nicotine-mediated increases in the excitability of the LDT could contribute to the differential susceptibility to nicotine addiction seen across...

  5. Poly-Alizarin red S/multiwalled carbon nanotube modified glassy carbon electrode for the boost up of electrocatalytic activity towards the investigation of dopamine and simultaneous resolution in the presence of 5-HT: A voltammetric study.

    Science.gov (United States)

    Reddaiah, K; Madhusudana Reddy, T; Venkata Ramana, D K; Subba Rao, Y

    2016-05-01

    Poly-Alizarin red S/multiwalled carbon nanotube film on the surface of glassy carbon electrode (poly-AzrS/MWCNT/GCE) was synthesized by electrochemical process and was used for the sensitive and selective determination of dopamine (DA) by employing voltammetric techniques. The electrocatalytic response of the modified electrode was found to exhibit admirable activity. The simultaneous determination of dopamine in the presence of serotonin (5-HT) was found to exhibit very good response at poly-AzrS/MWCNTs/GCE. The effect of pH, scan rate, accumulation time and concentration of dopamine was studied at the developed poly-AzrS/MWCNTs/GCE. The poly-AzrS/MWCNTs/GCE exhibited an efficient electron mediating behavior together with well resolved peaks for dopamine, in 0.1mol/dm(3) phosphate buffer (PBS) solution of pH7.0. The limit of detection (LOD) and limit of quantification (LOQ) were found to be as 1.89×10(-7)mol/dm(3) and 6.312×10(-7)mol/dm(3) respectively with a dynamic range from 1×10(-6) to 1.8×10(-5)mol/dm(3). The interfacial electron transfer behavior of DA was studied by electrochemical impedance spectroscopy (EIS); the studies showed that the charge transfer rate was enhanced at poly-AzrS/MWCNTs/GCE when compared with bare GCE and poly-AzrS/GCE. PMID:26952453

  6. Differentiation of a teratocarcinoma line: preferential development of cholinergic neurons

    OpenAIRE

    1981-01-01

    A line of embryonal carcinoma cells, PCC7-S, established in vitro from a spontaneous testicular teratocarcinoma, has been studied. Upon removing the cells from a low density monolayer culture system and permitting the cells to form aggregates in suspension, we observed a change of several physical and biochemical parameters: (a) reduction in average cell volume, (b) blockage and accumulation of cells in G1, (c) rise in secreted protease activity, (d) rise in acetylcholinesterase and choline a...

  7. Electron microscopic localization of M2-muscarinic receptors in cholinergic and noncholinergic neurons of the laterodorsal tegmental and pedunculopontine nuclei of the rat mesopontine tegmentum.

    Science.gov (United States)

    Garzón, Miguel; Pickel, Virginia M

    2016-10-15

    Muscarinic m2 receptors (M2Rs) are implicated in autoregulatory control of cholinergic output neurons located within the pedunculopontine (PPT) and laterodorsal tegmental (LTD) nuclei of the mesopontine tegmentum (MPT). However, these nuclei contain many noncholinergic neurons in which activation of M2R heteroceptors may contribute significantly to the decisive role of the LTD and PPT in sleep-wakefulness. We examined the electron microscopic dual immunolabeling of M2Rs and the vesicular acetylcholine transporter (VAchT) in the MPT of rat brain to identify the potential sites for M2R activation. M2R immunogold labeling was predominately seen in somatodendritic profiles throughout the PPT/LTD complex. In somata, M2R immunogold particles were often associated with Golgi lamellae and cytoplasmic endomembrannes, but were rarely in contact with the plasma membrane, as was commonly seen in dendrites. Approximately 36% of the M2R-labeled somata and 16% of the more numerous M2R-labeled dendrites coexpressed VAchT. M2R and M2R/VAchT-labeled dendritic profiles received synapses from inhibitory- and excitatory-type axon terminals, over 88% of which were unlabeled and others contained exclusively M2R or VAchT immunoreactivity. In axonal profiles M2R immunogold was localized to plasmalemmal and cytoplasmic regions and showed a similar distribution in many VAchT-negative glial profiles. These results provide ultrastructural evidence suggestive of somatic endomembrane trafficking of M2Rs, whose activation serves to regulate the postsynaptic excitatory and inhibitory responses in dendrites of cholinergic and noncholinergic neurons in the MPT. They also suggest the possibility that M2Rs in this brain region mediate the effects of acetylcholine on the release of other neurotransmitters and on glial signaling. J. Comp. Neurol. 524:3084-3103, 2016. © 2016 Wiley Periodicals, Inc. PMID:27038330

  8. Financing maneuvers. Two opportunities to boost a hospital's working capital.

    Science.gov (United States)

    Ferconio, S; Lane, M R

    1991-10-01

    Two receivables financing approaches, factoring and asset-backed securitization, offer an initial cash flow boost and a predictable source for continual cash flow. In a typical receivables factoring program, a healthcare organization receives advance funding from its receivables and reduces collection and follow-up efforts required of its staff. In exchange, the organization: Sells receivables at a discount between 5 percent and 10 percent off face value; and Pays a factoring fee of up to 20 percent of sold receivables. In a typical asset-backed securitization: Proceeds generated from the sale of A1-rated commercial paper are used to purchase receivables from a hospital; Accounts receivable eligible for sale are advance-funded at a level between 80 and 90 percent, with the unfunded portion remaining an asset of the hospital; The hospital is responsible for collection and follow-up activities; and An asset manager maintains cash collections to retire commercial paper notes and pay administrative costs. A healthcare organization interested in receivables financing should review each option's structure and benefits to assess advance funding provided, costs, a seller's level of control, and program eligibility requirements. PMID:10145512

  9. The cholinergic system in the olfactory center of the terrestrial slug Limax.

    Science.gov (United States)

    Matsuo, Ryota; Kobayashi, Suguru; Wakiya, Kyoko; Yamagishi, Miki; Fukuoka, Masayuki; Ito, Etsuro

    2014-09-01

    Acetylcholine plays various important roles in the central nervous system of invertebrates as well as vertebrates. In the olfactory center of the terrestrial slug Limax, the local field potential (LFP) oscillates, and the change in its oscillatory frequency is thought to correlate with the detection of odor that potentially changes an ongoing behavior of the animal. Acetylcholine is known to upregulate the frequency of the LFP oscillation, and is one of the candidates for the neurotransmitters that are involved in such higher cognitive functions. However, there have been no histological data on the cholinergic system in gastropods, nor are there data on the receptors that are responsible for the upregulation of the oscillatory frequency of LFP due to the lack of analytical tools (such as antibodies or cDNA sequence information on cholinergic system-related genes). Here we cloned the cDNAs of choline acetyltransferase (ChAT), acetylcholinesterase, vesicular acetylcholine transporter, and several nicotinic acetylcholine receptors (nAChRs), and investigated their localization in the brain of Limax. We also generated a polyclonal antibody against ChAT to examine its localization, and investigated pharmacologically the involvement of nAChRs in the LFP oscillation. Our data showed: 1) dense distribution of the neurons expressing mRNAs of ChAT and vesicular acetylcholine transporter in the olfactory center; 2) spatially unique expression patterns of different nAChRs in the olfactory center; 3) involvement of nAChRs in the upregulation of the oscillation; 4) localization of ChAT protein in nerve fibers and/or terminals; and 5) the presence of cholinergic nerves in the tentacles. PMID:24523205

  10. [The role of the basal forebrain cholinergic dysfunction in pathogenesis of declarative memory disorder in Alzheimer's disease].

    Science.gov (United States)

    Mukhin, V N

    2013-06-01

    Alzheimer's disease is the most common cause of the declarative memory disorder: 30-40% cases of dementia among all of age groups, and 50-60% among the people older 65 years. In addition, disorder of declarative memory is the genuine symptom of the disease, which certainly appears on early stage of the disease and it is an obligate diagnostic symptom. Proponents of the "cholinergic theory" of pathogenesis of Alzheimer's disease suggest that the basis disorder of declarative memory is cholinergic dysfunction. Several neurodynamic mechanisms associated with declarative memory depend on the level of acetylcholine in hippocampus and neocortex. It is believed that dysfunction of the basal cholinergic system in Alzheimer's disease leads to the impairment of these mechanisms. In this review, we summarize available literature data concerning the mechanisms of Alzheimer's disease. PMID:24459876

  11. Failure of cholinergic stimulation to induce a secretory response from the rectal mucosa in cystic fibrosis.

    OpenAIRE

    Hardcastle, J; Hardcastle, P T; Taylor, C J; Goldhill, J

    1991-01-01

    The secretory response to cholinergic stimulation was investigated in rectal biopsy specimens from children with cystic fibrosis and a control group using a modified Ussing chamber technique. Acetylcholine (10(-3) mol/l) increased the short circuit current in 12 control specimens by mean (SEM) 83.0 (16.4) microA/cm2, but samples from five children with cystic fibrosis failed to exhibit such a response (-1.4 (3.2) microA/cm2). Amiloride (10(-4) mol/l), which will inhibit electrogenic sodium ab...

  12. Cholinergic component in the human pancreatic secretory response to intraintestinal oleate.

    OpenAIRE

    Valenzuela, J E; Lamers, C B; Modlin, I. M.; Walsh, J H

    1983-01-01

    To determine the role of cholinergic reflexes on pancreatic secretory response to food, we studied the effect of atropine on amylase secretion in response to the octapeptide of cholecystokinin (CCK8) and to intraintestinal oleate. Four studies were done in six healthy volunteers. The duodenal content was aspirated by a double lumen tube while synthetic secretin (41 pmol/kg/h) was infused as a background in all the studies. Graded doses of CCK8 IV or 0.42 M oleate pH 9.4 at 25 ml/h into the in...

  13. Choline Acetyltransferase Activity in Striatum of Neonatal Rats Increased by Nerve Growth Factor

    Science.gov (United States)

    Mobley, William C.; Rutkowski, J. Lynn; Tennekoon, Gihan I.; Buchanan, Karen; Johnston, Michael V.

    1985-07-01

    Some neurodegenerative disorders may be caused by abnormal synthesis or utilization of trophic molecules required to support neuronal survival. A test of this hypothesis requires that trophic agents specific for the affected neurons be identified. Cholinergic neurons in the corpus striatum of neonatal rats were found to respond to intracerebroventricular administration of nerve growth factor with prominent, dose-dependent, selective increases in choline acetyltransferase activity. Cholinergic neurons in the basal forebrain also respond to nerve growth factor in this way. These actions of nerve growth factor may indicate its involvement in the normal function of forebrain cholinergic neurons as well as in neurodegenerative disorders involving such cells.

  14. Potent T cell Responses Induced by Single DNA Vaccine Boosted with Recombinant Vaccinia Vaccine

    Institute of Scientific and Technical Information of China (English)

    Lianxing Liu; Chao Qiu; Yang Huang; Jianqing Xu; Yiming Shao

    2013-01-01

    Plasmid DNA,an effective vaccine vector,can induce both cellular and humoral immune responses.However,plasmid DNA raises issues concerning potential genomic integration after injection.This issue should be considered in preclinical studies.Tiantan vaccinia virus (TV) has been most widely utilized in eradicating smallpox in China.This virus has also been considered as a successful vaccine vector against a few infectious diseases.Potent T cell responses through T-cell receptor (TCR) could be induced by three injections of the DNA prime vaccine followed by a single injection of recombinant vaccinia vaccine.To develop a safer immunization strategy,a single DNA prime followed by a single recombinant Tiantan vaccinia (rTV) AIDS vaccine was used to immunize mice.Our data demonstrated that one DNA prime/rTV boost regimen induced mature TCR activation with high functional avidity,preferential T cell Vβ receptor usage and high sensitivity to anti-CD3 antibody stimulation.No differences in T cell responses were observed among one,two or three DNA prime/rTV boost regimens.This study shows that one DNA prime/rTV boost regimen is sufficient to induce potent T cell responses against HIV.

  15. Control of heart rate during thermoregulation in the heliothermic lizard Pogona barbata: importance of cholinergic and adrenergic mechanisms.

    Science.gov (United States)

    Seebacher, F; Franklin, C E

    2001-12-01

    During thermoregulation in the bearded dragon Pogona barbata, heart rate when heating is significantly faster than when cooling at any given body temperature (heart rate hysteresis), resulting in faster rates of heating than cooling. However, the mechanisms that control heart rate during heating and cooling are unknown. The aim of this study was to test the hypothesis that changes in cholinergic and adrenergic tone on the heart are responsible for the heart rate hysteresis during heating and cooling in P. barbata. Heating and cooling trials were conducted before and after the administration of atropine, a muscarinic antagonist, and sotalol, a beta-adrenergic antagonist. Cholinergic and beta-adrenergic blockade did not abolish the heart rate hysteresis, as the heart rate during heating was significantly faster than during cooling in all cases. Adrenergic tone was extremely high (92.3 %) at the commencement of heating, and decreased to 30.7 % at the end of the cooling period. Moreover, in four lizards there was an instantaneous drop in heart rate (up to 15 beats min(-1)) as the heat source was switched off, and this drop in heart rate coincided with either a drop in beta-adrenergic tone or an increase in cholinergic tone. Rates of heating were significantly faster during the cholinergic blockade, and least with a combined cholinergic and beta-adrenergic blockade. The results showed that cholinergic and beta-adrenergic systems are not the only control mechanisms acting on the heart during heating and cooling, but they do have a significant effect on heart rate and on rates of heating and cooling. PMID:11815660

  16. Cholinergic cells in the nucleus basalis of mice express the N-methyl-D-aspartate-receptor subunit NR2C and its replacement by the NR2B subunit enhances frontal and amygdaloid acetylcholine levels

    NARCIS (Netherlands)

    De Souza Silva, M. A.; Dolga, Amalia; Pieri, I.; Marchetti, L.; Eisel, U. L. M.; Huston, J. P.; Dere, E.

    2006-01-01

    It is known that glutamatergic and cholinergic systems interact functionally at the level of the cholinergic basal forebrain. The N-methyl-D-aspartate receptor (NMDA-R) is a multiprotein complex composed of NR1, NR2 and/or NR3 subunits. The subunit composition of NMDA-R of cholinergic cells in the n

  17. Impaired hippocampal acetylcholine release parallels spatial memory deficits in Tg2576 mice subjected to basal forebrain cholinergic degeneration

    DEFF Research Database (Denmark)

    Laursen, Bettina; Mørk, Arne; Plath, Niels; Kristiansen, Uffe; Bastlund, Jesper Frank

    2013-01-01

    (BFCD) in 3 months old male Tg2576 mice to co-express cholinergic degeneration with Aβ overexpression as these characteristics constitutes key hallmarks of AD. At 9 months, SAP lesioned Tg2576 mice were cognitively impaired in two spatial paradigms addressing working memory and mid to long-term memory...... cortex and the reduction was comparable between groups. Our results suggest that partial BFCD acts collectively with increased levels of Aβ to induce cognitive decline and to compromise cholinergic release. Tg2576 mice with BFCD may constitute a new and suitable AD mouse model to study the interrelations...

  18. Investigation of non-cholinergic acetylcholinesterase, and related peptides in an in vitro preparation of the substantia nigra

    OpenAIRE

    Whyte, Kathryn Antonia.; Greenfield, Susan.; Susan Greenfield

    2001-01-01

    The primary role of acetylcholinesterase (AChE) is hydrolysis of acetylcholine (ACh). However, observations by numerous groups have suggested that AChE may have non-cholinergic functions. Furthermore, developmental roles for AChE and its related enzyme, butyrylcholinesterase (BuChE), which is also capable of ACh hydrolysis, have been postulated. One line of evidence to support a non-cholinergic role for AChE is the apparent disparity in several brain areas between the distribu...

  19. Intake Manifold Boosting of Turbocharged Spark-Ignited Engines

    Directory of Open Access Journals (Sweden)

    Lino Guzzella

    2013-03-01

    Full Text Available Downsizing and turbocharging is a widely used approach to reduce the fuel consumption of spark ignited engines while retaining the maximum power output. However, a substantial loss in drivability must be expected due to the occurrence of the so-called turbo lag. The turbo lag results from the additional inertia that the turbocharger adds to the system. Supplying air by an additional valve, the boost valve, to the intake manifold can be used to overcome the turbo lag. This turbo lag compensationmethod is referred to as intakemanifold boosting. The aims of this study are to show the effectiveness of intake manifold boosting on a turbocharged spark-ignited engine and to show that intake manifold boosting can be used as an enabler of strong downsizing. Guidelines for the dimensioning of the boost valve are given and a control strategy is presented. The trade-off between additional fuel consumption and the consumption of pressurized air during the turbo lag compensation is discussed. For a load step at 2000 rpm the rise time can be reduced from 2.8 s to 124ms, requiring 11.8 g of pressurized air. The transient performance is verified experimentally by means of load steps at various engine speeds to various engine loads.

  20. Scalar Controlled Boost PWM Rectifier for Micro Wind Energy Systems

    Directory of Open Access Journals (Sweden)

    J. Chelladurai

    2015-05-01

    Full Text Available Uses of Permanent Magnet Synchronous Generators (PMSG are increasing in variable speed micro-Wind Energy Conversion Systems (WECS. In stand-alone or grid-connected Micro-WECS, extraction of maximum power is vital. To extract maximum power output and to obtain a constant DC bus voltage from variable magnitude and variable frequency voltage output of PMSG and generally a two stage scheme namely i conventional diode bridge rectifier and ii DC-DC Boost/Buck/Buck-Boost converters are used. In this study, a single stage Scalar Controlled PWM (SCPWM Boost Rectifier is proposed in order to minimize the current harmonics and to improve the power factor on source side. The modeling and simulation of PMSG based wind generator and SCPWM Boost rectifier was developed in MATLAB. The harmonic content in the input current waveform of the proposed SCPWM rectifier is compared with the conventional three-phase bridge rectifier. The Simulation results show the effectiveness of the PWM Boost rectifier in terms of effective utilization of source, improved efficiency and harmonic mitigation for PMSG based Wind Generator. Simulation results demonstrate the effectiveness of the proposed system in reducing the current and voltage THD on source side.